PMID- 15426968
TI  - Laboratory diagnosis of fevers in the tropics.

PMID- 15426969
TI  - A case of recurrent eclampsia.

PMID- 15426970
TI  - Psychoneurosis in ophthalmic practice.

PMID- 15426971
TI  - Intragastric drip therapy of peptic ulcer.

PMID- 15426972
TI  - Antibiotics in tuberculosis.

PMID- 15426973
TI  - What's new in thyroid surgery.

PMID- 15426974
TI  - What's new in cardiovascular surgery.
AB  - Advances in the treatment of congenital cardiovascular lesions have led to a
      renewed interest in the treatment of acquired heart disease. Although this field
      could best be served by the perfection of the extracorporal heart, such devices
      are as yet not ready for human application. Meanwhile, various approaches through
      the ventricles and left atrium have been developed to treat valvular stenosis.
      Refinements in diagnostic tests and in methods of physiological investigation are
      of great aid in the proper evaluation of patients.

PMID- 15426975
TI  - What's new in isotopes, 1950.

PMID- 15426976
TI  - The background of delinquency.

PMID- 15426977
TI  - Leading causes of childhood death.
AB  - The over-all rates of death in childhood decreased five to ten fold during the
      first half of the century, with the greatest drop occurring in deaths due to
      infections. The death rate due to accidents has shown a relatively slight
      decrease; hence, accidents are now the leading cause of childhood death, and in
      California account for 32 per cent of the deaths in the group 1 to 15 years of
      age. In California, and among certain insured groups of children, cancer is the
      leading or second leading cause of death due to disease. There is indication that
      the incidence of leukemia is increasing in early childhood and in the older age
      groups.Accidents, the leading cause of childhood death, do not happen; they are
      caused, and so can be prevented. The medical profession should concern itself
      much more actively in the field of accident prevention.

PMID- 15426978
TI  - Chronic ulcerative colitis--psychosomatic factors.
AB  - In six cases of idiopathic ulcerative colitis here reported, close correlation
      with emotional stress was shown. Psychosomatic relationship seemed definite.
      Experience with 85 patients with ulcerative colitis has led to the suggestion
      that emotional stress may be causative or a predisposing factor in some, perhaps
      all, such cases.

PMID- 15426979
TI  - Diagnosis and differential diagnosis of poliomyelitis; the management of patients
      in the hospital admitting room.
AB  - Because of the great variety of early symptoms of poliomyelitis and their
      similarity to the symptoms of a number of other diseases, in times of epidemic
      many patients are admitted to hospital on suspicion of poliomyelitis. At such
      times the prime purpose of the hospital admitting room staff is to distinguish
      between patients with poliomyelitis (or other diseases requiring immediate
      treatment) and those who may be referred into other channels. This presentation
      (1) points out the superficial similarities of the clinically observable signs
      and symptoms and of laboratory data in poliomyelitis and in other diseases, and
      (2) discusses the more occult dissimilarities which aid in differentiation.

PMID- 15426980
TI  - Endemism of Coccidioidomycosis in the Paraguayan Chaco.
AB  - Skin testing of 541 men with coccidioidin was carried out in an investigation of
      endemism of coccidiodomycosis in the Paraguayan Chaco. In two areas where the
      climate is hot, dry and windy, positive reactions developed in a considerable
      number of the employees of an oil company who were of various racial origins, as
      well as among native Indians. In a third area, where rain is more plentiful and
      vegetation lush, only 2 per cent of 250 Indians tested had positive reaction to
      coccidioidin.

PMID- 15426981
TI  - Cytology of the postnasal drip.
AB  - About half of a series of 100 consecutive patients with disturbances of the eyes,
      ears, nose or throat complained of postnasal drip. When smears of the mucous
      discharge were examined it was found that in about a third of the cases in which
      there was complaint of drip, neither eosinophils nor neutrophils could be
      demonstrated. This indicates that causes of the drip other than allergic disease
      and infection must be considered.Cytologic examination of the postnasal drip
      showed that about one-third of the patients with nasal disease or histories
      positive for allergic reaction had nasal eosinophilia. Nasal eosinophilia was
      noted occasionally in patients with normal-appearing nasal structures and in
      patients with no history of allergic disease.

PMID- 15426982
TI  - Anuria and oliguria; treatment by conservative means, case report, with
      determination of blood volume and Na24 space.

PMID- 15426983
TI  - Allergic sinusitis treated as a deficiency disease.

PMID- 15426984
TI  - Barnyard fowl as a source of human ornithosis.

PMID- 15426985
TI  - Antabus and the metabolism of alcohol.
AB  - Antabus does not alter the rate of alcohol metabolism in dogs. It interferes with
      the metabolism of acetaldehyde, so that the ordinarily prompt removal of this
      substance from the tissues as it is produced in the metabolism of alcohol does
      not take place. It seems reasonable to assume that it is this accumulation of
      acetaldehyde in the tissues in abnormally high concentrations that is responsible
      for the unpleasant symptoms following the taking of alcohol by a patient
      receiving antabus.

PMID- 15426986
TI  - Antabus in the treatment of alcoholism in a private general hospital.
AB  - In 35 consecutive cases in which patients were admitted to a private hospital for
      alcoholism, antabus was contraindicated for eight patients and administered to
      27. Sixteen patients, followed three to nine months, cooperated fully with
      treatment and did not return to use of alcohol. In four cases there was at least
      one episode of drinking, but the patients continued to cooperate with treatment
      and attained partial success. In seven cases, including three in which antabus
      was stopped because of organic disease, treatment was unsuccessful. Insufficient
      insight and lack of family cooperation accounted for four failures. The presence
      of cardiovascular or hepatic diseases contraindicates antabus. As the test of
      reaction to alcohol after antabus has been given is hazardous, continuous
      supervision by nurse and physician throughout the test reaction is mandatory.
      Sustained results depend upon psychotherapy, family cooperation, careful follow
      up, and control of side-reactions to the drug. Antabus as an antagonist to
      alcohol is not safe enough to permit general use of the drug.

PMID- 15426987
TI  - The use of antabus in the therapy of alcoholic patients.
AB  - Preliminary studies on the effects of antabus (tetraethylthiuram disulfide) in
      the therapy of alcoholic patients indicate that it is very valuable in providing
      a "chemical foundation" for sobriety, even in those with a severe, long term
      drinking problem. In the first 30 patients treated, a favorable degree of control
      of the alcoholism has been effected in approximately 80 per cent. When taken
      regularly the drug maintains in the patient a very high degree of sensitivity to
      alcohol, quickly producing a number of very distressing bodily reactions whenever
      even very small amounts of spirits are ingested. Because of its potential
      dangers, antabus should be used only after thorough clinical and laboratory
      studies in properly staffed institutions. It is contraindicated in individuals
      with existing major psychosis or drug addiction and must be used only with
      caution in patients with diabetes mellitus, cardiovascular disease, goiter,
      pregnancy, epilepsy, asthma, and hepatic disease. Antabus therapy should be
      considered only one aspect of the total treatment program for the alcoholic
      patient.

PMID- 15426988
TI  - A survey of the results of treatment of gastric cancer in San Francisco.
AB  - A survey was made of all patients treated for gastric cancer on the clinic
      services of the Stanford University Hospital during the 30-year period 1919 to
      1948. During the last decade of the survey there were impressive gains in the
      surgical treatment of this disease. It was possible from 1944 to 1948 to do a
      gastric resection on half the patients seen with cancer of the stomach. Also,
      there was a pronounced decrease in resection mortality so that from 1939 to 1948
      the mortality rate for subtotal gastrectomy for cancer was 3 per cent. The over
      all five-year survival rate was discouragingly low-4.6 per cent. On the other
      hand, 23 per cent of those surviving gastric resection lived for five years.A
      survey of the management of carcinoma of the stomach from 1939 to 1948 was made
      in 11 general hospitals in San Francisco. A wide range of resectability and
      resection mortality rates was observed. The cases from these hospitals were
      combined with those from Stanford for the same period to form a composite group
      of 1,128 patients. Analysis of this group of cases from 12 representative
      hospitals in San Francisco showed encouraging trends toward higher resectability
      rates with a lower resection mortality.

PMID- 15426989
TI  - Carcinoma of the esophagus and gastric cardia, with special reference to
      treatment.
AB  - During the last five years the thoracic and abdominothoracic approaches in
      esophageal and gastric surgery have become established. With improvements in
      surgical and anesthetic technique mortality rates have declined. Preoperative and
      postoperative care are of great importance.

PMID- 15426990
TI  - Gastric resection; preoperative and postoperative care.
AB  - Perhaps in no other field of surgery does attention to minute detail play so
      important a role in determining success as it does in gastric operations. As
      surgery of the stomach develops toward even greater security and favorable
      results can be expected with greater confidence, the several aspects of
      preoperative and postoperative care hitherto regarded as secondary demand closer
      consideration.

PMID- 15426992
TI  - The administration of anticoagulants.
AB  - Heparin is administered parenterally. Its therapeutic effect is measured by the
      clotting time of the whole blood, determined by the method of Lee and White. An
      excessive anticoagulant effect is controlled by the administration of specific
      antagonists, toluidine blue or protamine sulfate. Dicumarol* is admintered orally
      in amounts sufficient to reduce the prothrombin activity of the plasma to between
      10 and 30 per cent of normal. The prothrombin time, which represents such a
      reduction in prothrombin activity, will vary according to the method by which the
      determination is performed, the thromboplastin used, and the technique followed.
      Excessive prolongation of the prothrombin time is antagonized by the
      administration of vitamin K in large doses. Long-term therapy with Dicumarol is
      sufficiently hazardous to require considerable experience on the part of the
      physician. Where an immediate anticoagulant effect is necessary, yet prolonged
      administration anticipated, combined therapy with both heparin and Dicumarol may
      be used until the prothrombin time is prolonged satisfactorily, whereupon heparin
      may be discontinued.

PMID- 15426991
TI  - Dicumarol and quinidine in the ambulatory treatment of chronic auricular
      fibrillation.
AB  - Thirty-three patients with chronic auricular fibrillation were treated with
      digitalis and quinidine and in addition were given Dicumarol(R) to reduce the
      risk of embolism. In 21 of the patients the fibrillation was caused by rheumatic
      heart disease, and in 12 by arteriosclerosis or hypertension. Normal sinus rhythm
      was restored in 55 per cent of the 33 patients, in 67 per cent of those with
      arteriosclerosis or hypertension, and in 45 per cent of those with rheumatic
      heart disease. Embolism did not occur.

PMID- 15426993
TI  - A simple electrosurgical treatment of rhinophyma.

PMID- 15426994
TI  - Adrenocortical tumors.
AB  - Hormonally active tumors of the adrenal cortex are either benign adenomas or
      adenocarcinomas. They may be located within the adrenal gland or as adrenal rests
      along the Wolffian tract. Hyperplastic cortical tissue without actual neoplastic
      formation is also capable of elaborating excessive cortical secretions.AT THE
      PRESENT STATE OF KNOWLEDGE, ANY ONE OR A COMBINATION OF THE FOLLOWING COMPOUNDS
      MAY BE ELABORATED IN A GIVEN CASE: the electrolytic, glucogenic, androgenic, or
      estrogenic corticosteroids. Whether or not Cushing's syndrome is primarily
      pituitary or adrenal in origin is still a matter of conjecture.

PMID- 15426995
TI  - Amebic abscess of the liver.
AB  - In a review of the records in 50 cases of amebic abscess of the liver observed in
      the Canal Zone between 1920 and 1945 the following features were noted:Incidence
      was preponderantly in males and highest in persons between the ages of 20 and 40.
      None of the patients was under 21 years of age. There was a great variety of
      complaints at the time of admission to hospital. The most common was pain in the
      right upper quadrant of the abdomen. Demonstration of either elevated or fixed
      diaphragm by x-ray film and fluoroscopic examination was useful in diagnosis in a
      number of cases, but absence of such findings did not rule out abscess of the
      liver. In some cases there was history of previous dysentery with blood in the
      stools.One or another of three operative procedures was used for drainage of
      abscesses in 39 patients. Of the 39, six died; in five of the six, multiple
      abscesses were present. Emetine hydrochloride was given to all patients.

PMID- 15426996
TI  - Rehabilitation of patients with hemiplegia.
AB  - Many patients with hemiplegia can be rehabilitated. Physiological reflexes may be
      used in attempting to establish patterns of motion and are of definite aid in
      overcoming contractures. Physical and occupational therapy is of value.

PMID- 15426997
TI  - Toxicology of organic phosphate insecticides.
AB  - The development of effective new insecticides has created potential industrial
      health hazards to people engaged in their manufacture and application, as well as
      to those with casual exposures. A group of these insecticides known as the
      organic phosphates is extremely toxic, destroying the enzyme cholinesterase and
      exerting a cholinergic action on the mammalian animal. A discussion of the
      origin, chemistry, and pharmacology of these compounds, along with a description
      of symptoms, diagnosis and treatment of poisoning is presented. Methods of
      prevention of poisoning and control measures for the safe use of these compounds
      are described.

PMID- 15426999
TI  - Electrocardiogram immediately before and after septal infarction; report of a
      case.

PMID- 15426998
TI  - Homologous serum hepatitis following operation on the biliary tract; report of 3
      cases.

PMID- 15427000
TI  - Tuberculous fistula in a postpartum uterus; report of a case.

PMID- 15427001
TI  - Medical technicians: the present need and training in California.

PMID- 15427002
TI  - Training of hospital administrators; existing facilities here and elsewhere.

PMID- 15427003
TI  - The Princess Elizabeth Hospital.

PMID- 15427004
TI  - [Non-professional personnel in the patients service].

PMID- 15427006
TI  - Hospitals and the radio.

PMID- 15427005
TI  - Hospitals and the press.

PMID- 15427007
TI  - HANDSOME structure to replace present Bowmanville Hospital.

PMID- 15427008
TI  - Evaluating the status of the hospital orderly.

PMID- 15427010
TI  - MEDICAL services in Newfoundland.

PMID- 15427009
TI  - BEAUTY service as a therapy.

PMID- 15427011
TI  - Pursuing accuracy and completeness in medical records.

PMID- 15427012
TI  - MARITIME Hospital Convention.

PMID- 15427013
TI  - APPETIZING recipes.

PMID- 15427014
TI  - Algal poisoning in Ontario.

PMID- 15427015
TI  - Liver rot (fascioloidiasis) in ruminants.

PMID- 15427017
TI  - Listeria monocytogenes in lemming.

PMID- 15427016
TI  - Vaccination of sexually mature cows with Brucella abortus strain 19 vaccine.

PMID- 15427018
TI  - Rupture of the gastrocnemius tendon in chickens.

PMID- 15427019
TI  - Some important swine diseases.

PMID- 15427020
TI  - Canine giardiasis and its treatment with atebrin.

PMID- 15427021
TI  - Report of a Salmonella (paratyphoid) survey in Alberta.

PMID- 15427022
TI  - Field treatment of a fracture in a heifer.

PMID- 15427023
TI  - Fish-borne and type E botulism: two cases due to home-pickled herring.

PMID- 15427024
TI  - Cancer mortality trends in different countries.

PMID- 15427025
TI  - Control of pollution by federal authorities.

PMID- 15427026
TI  - Poliomyelitis virus in urban sewage; an examination for its presence over a
      period of 12 months.

PMID- 15427027
TI  - Plague.

PMID- 15427028
TI  - Sanitation in a flooded area.

PMID- 15427029
TI  - The relationship of the census to public health.

PMID- 15427031
TI  - Eugeria.

PMID- 15427030
TI  - The medical officer of health in Great Britain.

PMID- 15427032
TI  - Signs of malnutrition in Canada.

PMID- 15427033
TI  - The value of sputum examination in diagnosis of cancer of the lung.

PMID- 15427034
TI  - Melanotic sarcoma.

PMID- 15427035
TI  - Some aspects of surgery of the stomach.

PMID- 15427036
TI  - Administrative medicine.

PMID- 15427037
TI  - Face and brow presentations.

PMID- 15427038
TI  - Malignant mischief.

PMID- 15427039
TI  - Tick paralysis.

PMID- 15427040
TI  - Posture in lung surgery.

PMID- 15427041
TI  - The plication operation in the treatment of peritoneal adhesions.

PMID- 15427042
TI  - The present status of orbital implants.

PMID- 15427043
TI  - Cysts of the lung and of the mediastinum.

PMID- 15427044
TI  - Consideration of the requirements and training of a plastic surgeon.

PMID- 15427045
TI  - Partial cholecystectomy.

PMID- 15427046
TI  - The plasma concentration of quinidine after oral administration and its effect on
      auricular fibrillation.

PMID- 15427047
TI  - The treatment of pain and "spasm" in poliomyelitis with "priscoline".

PMID- 15427048
TI  - Rheumatic pancarditis treated with cortisone.

PMID- 15427049
TI  - Synchronous lymphatic leukaemia bronchogenic carcinoma and hypernephroma.

PMID- 15427050
TI  - A case of exomphalos.

PMID- 15427051
TI  - Latent silicosis.

PMID- 15427052
TI  - Tuberculous pericarditis treated with streptomycin.

PMID- 15427053
TI  - Primary splenic neutropenia with rheumatoid arthritis. (Felty's syndrome).

PMID- 15427054
TI  - An outline of iron metabolism.

PMID- 15427055
TI  - Prostigmine vaginal suppositories in delayed menstruation.

PMID- 15427056
TI  - A new approach to the treatment of foot-drop.

PMID- 15427057
TI  - Distribution of medical service.

PMID- 15427058
TI  - Some observations on genius.

PMID- 15427059
TI  - Unskilful surgery.

PMID- 15427060
TI  - JOHN of Arderne and cancer of the rectum.

PMID- 15427061
TI  - Factors contributing to delay by patients in seeking medical care.

PMID- 15427062
TI  - The relation between the toxic action and the tumor-inhibiting power of some
      drugs.

PMID- 15427063
TI  - The metabolism of radioactive dibromoestrone in man.

PMID- 15427064
TI  - Hepatic dysfunction in candidates for abdominal surgery, especially in patients
      with cancer.

PMID- 15427065
TI  - Reoperation following pancreato-duodenectomy.

PMID- 15427066
TI  - Roentgenotherapeutic changes in the small intestine; surgical aspects.

PMID- 15427067
TI  - The spread of carcinoma of the colon and rectum.

PMID- 15427068
TI  - Mesenchymoma of the mesentery.

PMID- 15427069
TI  - Epidermoid carcinoma of the hand.

PMID- 15427070
TI  - Nonchromaffin paraganglioma of ganglion nodosum, carotid body, and aortic-arch
      bodies.

PMID- 15427071
TI  - Pituitary chromophobe tumors of the nasal cavity.

PMID- 15427072
TI  - Detection of cerebral tumors by ultrasonic pulses; pilot studies on postmortem
      material.

PMID- 15427073
TI  - The modification of resistance to ionizing radiation by humoral agents.

PMID- 15427074
TI  - The significance of low calcium and high potassium content in neoplastic tissue.

PMID- 15427075
TI  - Tumor-host studies. II. Increased concentration of tagged iodotyrosines in the
      gastrointestinal tract of rats bearing tumors.

PMID- 15427076
TI  - Quantitative differential fixation of sulfate by tissues maintained in vitro;
      sulfate fixation as a function of age for embryonic tissues.

PMID- 15427077
TI  - Studies on the influence of sex hormones on successful heterologous
      transplantation of human bronchogenic carcinoma.

PMID- 15427078
TI  - This business of cancer research.

PMID- 15427079
TI  - Tumors in the invertebrates: a review.

PMID- 15427080
TI  - Response of a transplantable lymphosarcoma to colchicine.

PMID- 15427081
TI  - Studies in Hodgkin's syndrome. X. The morphology and growth patterns of explant
      cells cultivated in vitro.

PMID- 15427082
TI  - The changes in the mitotic mechanism of human cancer cells.

PMID- 15427083
TI  - The virus-induced rabbit papilloma-to-carcinoma sequence. II. Carcinomas in the
      natural host, the cottontail rabbit.

PMID- 15427084
TI  - Serum polysaccharide levels in rats bearing the Walker 256 tumor.

PMID- 15427085
TI  - The effect of the proportion of dietary fat on the rate of formation of mammary
      carcinoma in mice.

PMID- 15427086
TI  - The effect of added dietary tryptophane on the occurrence of 2
      acetylaminofluorene-induced liver and bladder cancer in rats.

PMID- 15427087
TI  - [Unipolar electrocardiography of congenital anomalies of the heart].

PMID- 15427088
TI  - Mechanism of ventricular fibrillation.

PMID- 15427089
TI  - [Further investigations of the separator method; separator and
      electrocardiographic tracings of coronary circulation].

PMID- 15427090
TI  - [Medical progress in Germany].

PMID- 15427091
TI  - [Alkaloids content of Atropa belladonna L. in various stages of development].

PMID- 15427092
TI  - [Legislation on production and distribution of drugs].

PMID- 15427093
TI  - [Legislation on the sale of drugs].

PMID- 15427094
TI  - [The origin of drugs].

PMID- 15427095
TI  - [Alkaloid content of Datura stramonium L. in various stages of evolution].

PMID- 15427096
TI  - [Alkaloid content of Hyoscyamus niger L. in various stages of development].

PMID- 15427097
TI  - [In memory of Dobroslav Trousalik].

PMID- 15427098
TI  - [Possibilities of determination of salol in combination with thymol and chloride
      of pilocarpine in combination with chloride of novocaine].

PMID- 15427099
TI  - [Newer findings on preparation and properties of rutin].

PMID- 15427100
TI  - [New drugs].

PMID- 15427101
TI  - [Legislation concerning regulation of prices of medicinal plants growing in
      Czechoslovakia].

PMID- 15427102
TI  - [Penicillin; clinical use and dosage in veterinary medicine].

PMID- 15427103
TI  - [Puerperal sepsis in a mare successfully treated with penicillin].

PMID- 15427104
TI  - [Treatment of diseases in colts with penicillin].

PMID- 15427105
TI  - [Bronchopneumonia in horses treated with penicillin].

PMID- 15427106
TI  - [Sewage in abattoirs].

PMID- 15427107
TI  - [Agglutination titers and opsonin index following yatren autovaccine in horses
      with suppurative processes].

PMID- 15427108
TI  - [Impressions from the XIV. International Veterinary Congress in London].

PMID- 15427109
TI  - [Not Available].

PMID- 15427110
TI  - [Successful laparotomy for volvulus in a horse].

PMID- 15427111
TI  - [Electrocardiographic changes in high blood pressure].

PMID- 15427112
TI  - [Bactericidal effect of cadmium chloride on pseudodiphtherial Corynebacterium and
      its application in the laboratory diagnosis of diphtheria].

PMID- 15427113
TI  - [Spermatocidal effect of certain substances].

PMID- 15427114
TI  - [New possibilities in tomographic diagnosis].

PMID- 15427115
TI  - [Clinical experiences with synthetic alkaloid (partergin) in obstetrics].

PMID- 15427116
TI  - [Electrocardiographic findings of heart displacement in chronic cor pulmonale].

PMID- 15427117
TI  - [Filariasis in a patient returning from the tropics].

PMID- 15427118
TI  - [Possibilities of the treatment of acute pulmonary abscesses].

PMID- 15427119
TI  - [Case of priapism in hormonal therapy].

PMID- 15427120
TI  - [Use of rectal smears in epidemiology].

PMID- 15427121
TI  - [Renal enzymes and essential hypertension].

PMID- 15427122
TI  - [Night services in a psychiatric clinic in Olomuoc].

PMID- 15427123
TI  - [Internal medicine; past and future].

PMID- 15427124
TI  - [Antagonist of rutin and pelentan].

PMID- 15427125
TI  - [Pathogenesis and treatment of pancreatic cysts].

PMID- 15427126
TI  - [Diagnosis of obstructive atelectasis].

PMID- 15427127
TI  - [Modification of Tavernier's operation of arthrosis of the hip].

PMID- 15427128
TI  - [Infections with Salmonella typhimurium in premature babies].

PMID- 15427129
TI  - [Certain new media in the control of bacterial diseases].

PMID- 15427130
TI  - [Effect of antihistaminic substances on the metabolism of glucides; study of the
      mechanism of the effect of antihistaminic substances].

PMID- 15427131
TI  - [Pulmonary fibrosis in scleroderma].

PMID- 15427132
TI  - [Ollier's disease].

PMID- 15427133
TI  - [Spontaneous perforation of the diaphragm in a woman with pulmonary
      tuberculosis].

PMID- 15427134
TI  - [Decreasing the irritation caused by adhesive tape by using water solution of
      certain organic dyes].

PMID- 15427135
TI  - [Volvulus of the cecum in a 3-months-old child, cured after hemicolectomy].

PMID- 15427137
TI  - [An unusual case of dextroposition of the heart erroneously diagnosed as isolated
      dextrocardia].

PMID- 15427136
TI  - [Elimination of epithelial cells of the urinary tract].

PMID- 15427138
TI  - [Work of Dr. Jarosl. Snopek; contribution to the question of subdural hematoma].

PMID- 15427139
TI  - [An answer to the article by Dr. Ivan Lesny].

PMID- 15427140
TI  - [Sixty fifth anniversary of Dr. P. Trnka, the director of the regional hospital
      in Havli6ckove Brody].

PMID- 15427141
TI  - [Fiftieth birthday of Prof. Dr. Jan Knobloch].

PMID- 15427142
TI  - [Use of penicillin G in the treatment of syphilis].

PMID- 15427144
TI  - [Peptic ulcer and carcinoma of the stomach].

PMID- 15427143
TI  - [Biochemistry of iodine; colorimetric determination of iodine in urine].

PMID- 15427145
TI  - [Precordial pain with electrocardiographic changes as a postoperative
      complication].

PMID- 15427146
TI  - [Buscaino's reaction and its significance in athletics].

PMID- 15427147
TI  - [Examination of the bone marrow in histologic sections].

PMID- 15427148
TI  - [Benzene metabolism and its compounds in the human organism].

PMID- 15427149
TI  - [Case of chronic lymphatic leukemia with hypertrophic prostate and its therapy
      with urethane].

PMID- 15427150
TI  - [Effect of anesthesia of the stellate ganglion on bigeminy of long duration].

PMID- 15427151
TI  - [Color sensitivity in psychotic patients].

PMID- 15427152
TI  - [Case of acute rheumatic carditis with Cor. diphtheriae findings].

PMID- 15427153
TI  - [Planning of biologic and medical research].

PMID- 15427154
TI  - [Pavlov's teaching on nervous activities].

PMID- 15427155
TI  - [Experiments with potassium in dermatology].

PMID- 15427156
TI  - [Determination of skin injuries with weak solutions of alkali].

PMID- 15427157
TI  - [Experimental studies on sensitization effect of certain substances with benzene
      bases].

PMID- 15427158
TI  - [Experimental study of sublimate patch tests and the effect of antihistaminic
      drugs on the epidermoreaction].

PMID- 15427159
TI  - [Meaning and value of the biological test in blood transfusion].

PMID- 15427160
TI  - [Intraoperative blood transfusion].

PMID- 15427161
TI  - [Determining time and amount in blood transfusion prophylaxis of surgical shock].

PMID- 15427162
TI  - [Evaluation of methods of steam regulation in sterilization of dressings].

PMID- 15427163
TI  - [Structure and mechanism of the aortic wall, with reference to surgical therapy
      of isthmic stenosis].

PMID- 15427164
TI  - [Effect of goiter upon the trachea and the importance of preliminary roentgen
      examination in strumectomy].

PMID- 15427165
TI  - [Unsolved problems of vascular surgery].

PMID- 15427166
TI  - [New methods of examination in the diagnosis of fat embolism].

PMID- 15427167
TI  - [Pathologico-anatomic studies of breast cancer in preoperative radiotherapy].

PMID- 15427168
TI  - [Technic of laryngectomy].

PMID- 15427169
TI  - [Mixed nitrous oxide anesthesia in laryngectomy].

PMID- 15427170
TI  - [Treatment of habitual patellar dislocation].

PMID- 15427171
TI  - [Surgical therapy of exstrophy of the bladder].

PMID- 15427172
TI  - [Right-ventricle puncture in venous gas embolism].

PMID- 15427173
TI  - [Retropharyngeal and mediastinal abscess in three-week old infant].

PMID- 15427174
TI  - [Mistaken diagnosis of strangulated femoral hernia].

PMID- 15427175
TI  - [Pyloristenosis caused by a neurofibroma in a case of Recklinghausen's disease].

PMID- 15427176
TI  - [The pace-splint].

PMID- 15427177
TI  - [New finger extension].

PMID- 15427178
TI  - [Treatment of Douglas's abscess].

PMID- 15427179
TI  - [Professor Dr. Oskar Wiedhopf].

PMID- 15427180
TI  - [Gastric and duodenal surgery].

PMID- 15427181
TI  - [The wide transthoracic approach in the treatment of hydatid cysts of the upper
      portion of the liver].

PMID- 15427182
TI  - [Anatomical research on the depressor nerve].

PMID- 15427183
TI  - [Anesthetic infiltration and resection of the preaortic plexus].

PMID- 15427184
TI  - [A case of primary epithelioma of Bartholin's gland].

PMID- 15427185
TI  - [Clinical value of the bleeding nipple in fibrocystic disease of the breast].

PMID- 15427187
TI  - [Errors and failures in renal surgery].

PMID- 15427186
TI  - [Acute abdominal syndrome and acute mesenteric lymphoadenitis].

PMID- 15427188
TI  - [Articular chondromatosis in the works of Morgagni].

PMID- 15427190
TI  - NEW isotope laboratory.

PMID- 15427189
TI  - The pathogenesis of angina pectoris and some clinical implications.

PMID- 15427191
TI  - An integrating circuit for measurement of the areas of the waves in the
      electrocardiogram.

PMID- 15427192
TI  - Intracardiac and intravascular potentials resulting from electrical activity of
      the normal human heart.

PMID- 15427193
TI  - Peri-infarction block; electrocardiographic abnormality occasionally resembling
      bundle branch block and local ventricular block of other types.

PMID- 15427194
TI  - Excitation of human auricular muscle and the significance of the intrinsicoid
      deflection of the auricular electrocardiogram.

PMID- 15427195
TI  - Studies in intracardiac electrography in man; IV. the potential variations in the
      coronary venous.

PMID- 15427196
TI  - QRS-T patterns in multiple precordial leads that may be mistaken for myocardial
      infarction III. bundle branch block.

PMID- 15427197
TI  - Other QRS-T patterns that may be mistaken for myocardial infarction; IV.
      alterations in blood potassium; myocardial ischemia; subepicardial myocarditis;
      distortion associated with arrhythmias.

PMID- 15427198
TI  - Clinical electrocardiography--its present position and possible potentialities.

PMID- 15427199
TI  - Standardizing factors in electrocardiography.

PMID- 15427200
TI  - The validity of the equilateral tetrahedron as a spatial reference system.

PMID- 15427202
TI  - Comparison of heart vectors calculated with different systems of leads.

PMID- 15427201
TI  - An approximate derivation for stereoscopic vectorcardiograms with equilateral
      tetrahedron.

PMID- 15427203
TI  - Chronic pericarditis with effusion.

PMID- 15427204
TI  - Blood lipids and human atherosclerosis.

PMID- 15427205
TI  - Impending hemorrhagic shock and the course of events following administration of
      dibenamine.

PMID- 15427206
TI  - Changes in the ballistocardiogram after exercise in normal and abnormal subjects.

PMID- 15427207
TI  - The electrokymography; studies in recording fidelity.

PMID- 15427208
TI  - The interrelationships of serum cholesterol, cholesterol esters and phospholipids
      in health and in coronary artery disease.

PMID- 15427209
TI  - The effects of intravenous aminophylline upon the coronary blood-oxygen exchange.

PMID- 15427210
TI  - Blood vessels of the skin in chronic venous insufficiency.

PMID- 15427211
TI  - Effect of potassium and of desoxycorticosterone acetate in acute heart injury in
      the rat.

PMID- 15427212
TI  - Electrical effects of stimulating the endocardial surface of the right ventricle
      of the dog.

PMID- 15427213
TI  - Arrhythmias during intracardiac catheterization.

PMID- 15427214
TI  - Ventricular tachycardia during cardiac catheterization of patient with Wolff
      Parkinson-White syndrome; report of a case showing effects of atropine sulfate.

PMID- 15427215
TI  - Electrokymographic studies of the normal cardiac cycle.

PMID- 15427216
TI  - Abdominal aortic aneurysm; a study of one hundred and two cases.

PMID- 15427217
TI  - Sodium gentisate in the treatment of acute rheumatic fever.

PMID- 15427218
TI  - Studies on blood coagulation and the effect of digitalis.

PMID- 15427219
TI  - The use of digitalis in spite of the presence of ventricular tachycardia.

PMID- 15427220
TI  - Liver function tests in chronic congestive heart failure.

PMID- 15427221
TI  - Pericardial effusion mistaken for cardiac enlargement in severe anemia.

PMID- 15427222
TI  - Lodging of an embolus in a patent foramen ovale.

PMID- 15427223
TI  - [Current treatment of renal tuberculosis].

PMID- 15427224
TI  - [The permeability of the cornea].

PMID- 15427225
TI  - [Madelung's disease].

PMID- 15427226
TI  - [Vascular accidents in urethrocystography].

PMID- 15427228
TI  - [Location of the diaphragm].

PMID- 15427227
TI  - [Hematic regulation in hypophysectomized animals; hematic reaction to
      intracardiac adrenalin].

PMID- 15427229
TI  - [The problem of chronic cholecystitis].

PMID- 15427230
TI  - [Treatment of ulcer at the anastomotic mouth and gastrojejunocolic fistula].

PMID- 15427231
TI  - [The tubal factor in sterility; diagnosis by kymographic insufflation].

PMID- 15427232
TI  - [Postoperative variations in body fluids, plasma and blood proteins in urological
      patients].

PMID- 15427233
TI  - [Folic acid in tuberculous anemia].

PMID- 15427235
TI  - [Ultravirus infections].

PMID- 15427234
TI  - [Treatment of sexual impotence with associated testosterone and vitamin E].

PMID- 15427236
TI  - [Treatment of human brucellosis with aureomycin and the association of aureomycin
      and di-hydrostreptomycin].

PMID- 15427237
TI  - [Chloramphenicol in the treatment of typhoid infections].

PMID- 15427238
TI  - [Immunity in infectious diseases].

PMID- 15427239
TI  - [Artificial radioactive substances].

PMID- 15427241
TI  - [A year's observation on tuberculosis of children at the seashore].

PMID- 15427240
TI  - [Involuntary experiment on the resistance of vaccinated (Petragnani-Salvioli
      vaccine) and unvaccinated infants to highly infectious contact with tuberculosis.
      I. Report on the incident at Dolo and on the mortality in the two groups].

PMID- 15427243
TI  - The present status of pertussis immunization; progress report.

PMID- 15427242
TI  - The use of chloramphenicol (chloromycetin) in the treatment of infections of the
      urinary tract in childhood; special report.

PMID- 15427244
TI  - Primary encephalitis of undetermined virus etiology.

PMID- 15427245
TI  - Cyanosis in an infant with dextrocardia, situs inversus, and tricuspid atresia.

PMID- 15427246
TI  - CLINICO-pathological conference; atrophy of the left kidney and cystic
      degeneration of right kidney with bilateral hydroureteronephrosis due to
      obstruction by a congenital valve in the prostatic urethra.

PMID- 15427247
TI  - [Juvenile female obesity of the spongious type].

PMID- 15427248
TI  - [Management of phlebitis].

PMID- 15427249
TI  - [Biologic studies of the hemostatic function].

PMID- 15427250
TI  - [Diagnosis and treatment of amenorrhea].

PMID- 15427251
TI  - [Implantation of crystallized hormones].

PMID- 15427252
TI  - [Diagnosis and treatment of male sterility].

PMID- 15427253
TI  - [Treatment of agranulocytosis].

PMID- 15427254
TI  - [Indications of vaccinotherapy in asthma].

PMID- 15427255
TI  - [Combined methods in induction of labor near term].

PMID- 15427256
TI  - [Acute articular rheumatism in pregnancy, treated with habitual method and
      followed by abortion].

PMID- 15427257
TI  - [What all physicians should know about modern principles of fracture therapy].

PMID- 15427258
TI  - [What all physicians should know about Kuntscher's intermedullary nailing].

PMID- 15427259
TI  - [Diagnosis of vaginitis due to trichomonas and its therapy].

PMID- 15427260
TI  - [Indications of sodium chloride cure in gynecology].

PMID- 15427261
TI  - [Sarcoma of the cervix uteri].

PMID- 15427262
TI  - [Difficulty of differential diagnosis of cysts and fibroma].

PMID- 15427263
TI  - [Smears of the fundus uteri in the study of ascent of spermatozoa].

PMID- 15427264
TI  - [Effect of amyl-nitrate in spasmodic tubal stenosis].

PMID- 15427265
TI  - [Prognosis of tuberculosis of the genital tract diagnosed by biopsy of the
      endometrium].

PMID- 15427266
TI  - [Certain tests of respectability].

PMID- 15427267
TI  - [Dangers in osteosynthesis].

PMID- 15427268
TI  - [Encephaloid form of secondary cancer of the liver].

PMID- 15427269
TI  - [Polycystic disease of the kidneys in a stillborn].

PMID- 15427270
TI  - [Hemorrhoid allergy].

PMID- 15427271
TI  - [Preferential benignity of congenital syphilis].

PMID- 15427272
TI  - [Treatment of gonorrhea in women].

PMID- 15427273
TI  - [Hormone treatment of the shock with desoxycorticosterone].

PMID- 15427274
TI  - [Does Social Security cover the financing of hospital equipment?].

PMID- 15427275
TI  - [Occupational accidents and Social Security].

PMID- 15427276
TI  - [Hygiene in the industry in the United States].

PMID- 15427277
TI  - [Geriatrics].

PMID- 15427278
TI  - [Diagnosis of migraine with complications].

PMID- 15427279
TI  - [Non-bacterial pyuria].

PMID- 15427280
TI  - [Early diagnosis of acute intestinal invagination and barium enema].

PMID- 15427281
TI  - [Inadequacy of Widal's serodiagnosis to confirm typhoid fever].

PMID- 15427282
TI  - [Contribution to the study of activation of electroencephalogram by cardiazol].

PMID- 15427283
TI  - [Intestinal lithiasis].

PMID- 15427284
TI  - [The Social Security in relation to treatment of the physician's family].

PMID- 15427285
TI  - [Outline for a reform of the Social Security].

PMID- 15427286
TI  - [Visit to the service "Sloan-Kattering" of the Memorial Hospital of New York].

PMID- 15427287
TI  - [Sanitation measures in Italy during the Holy Year].

PMID- 15427288
TI  - [Vitamins in the plant physiology].

PMID- 15427289
TI  - [Collectivistic housekeeping].

PMID- 15427290
TI  - [Pseudo-cancerous forms of tuberculous peritonitis].

PMID- 15427291
TI  - [The Thorn test].

PMID- 15427292
TI  - [Calmette-Guerin bacillus or B.C.G..].

PMID- 15427293
TI  - [Old age allowances for doctors; disability commissions].

PMID- 15427295
TI  - [Treatment of diabetes mellitus].

PMID- 15427294
TI  - [Police women].

PMID- 15427296
TI  - [Tuberculous lymphoma].

PMID- 15427297
TI  - [Can a doctor refuse to treat persons with social insurance?].

PMID- 15427298
TI  - [Cranial hyperostosis].

PMID- 15427300
TI  - [Basic, classical views in radiography of the temporal bone].

PMID- 15427299
TI  - [Radiography of the petromastoid region].

PMID- 15427301
TI  - [Precise radiography of the temporal bone].

PMID- 15427302
TI  - [Radiography of the orbit in oto-neuro-ophthalmology].

PMID- 15427303
TI  - Breast cancer.

PMID- 15427304
TI  - The role of potassium in medical therapy.

PMID- 15427306
TI  - A review of wound disruptions.

PMID- 15427305
TI  - Dysphagia and dysphonia as symptoms of cancer.

PMID- 15427307
TI  - Torsion of the gallbladder.

PMID- 15427308
TI  - Antemortem diagnosis of the perforated interventricular septum.

PMID- 15427309
TI  - Pediatric and psychiatric aspects of the Yale Rooming-In Project.

PMID- 15427310
TI  - The increasing incidence of cesarean section.

PMID- 15427311
TI  - Seth Bird and his friends.

PMID- 15427312
TI  - Role of county society members in medical legislation.

PMID- 15427313
TI  - The semen of the thoroughbred.

PMID- 15427314
TI  - Six congenital cardiac anomalies in animals.

PMID- 15427315
TI  - Possible congenital anomaly and rupture of the ureter in a yearling bull.

PMID- 15427316
TI  - Aureomycin as a treatment of acute brucellosis of cattle.

PMID- 15427317
TI  - Two cases of fracture in the horse.

PMID- 15427318
TI  - Anesthetization of white-tailed deer.

PMID- 15427319
TI  - A case of posterior paralysis in a cow.

PMID- 15427320
TI  - Fracture of the tibia in a cow.

PMID- 15427321
TI  - The anemias in the trichostrongylidoses.

PMID- 15427322
TI  - Studies on Newcastle disease; viability of live embryo Newcastle disease virus in
      buffered glycerol.

PMID- 15427323
TI  - Fibropapillomas of the external genitalia of cattle.

PMID- 15427324
TI  - The urease activity of certain pathogenic microorganisms isolated from animals.

PMID- 15427325
TI  - Experimental transmission of the deer lungworm Leptostrongylus alpenae.

PMID- 15427326
TI  - Follicular cyst in a horse.

PMID- 15427327
TI  - The sociologist looks to the profession of anesthesiology.

PMID- 15427328
TI  - Position of the anesthesiologist on the hospital staff.

PMID- 15427329
TI  - Indications for music in anesthesia.

PMID- 15427330
TI  - Choice of methods for conduction anesthesia in obstetrics.

PMID- 15427331
TI  - The intravenous use of alcohol in surgery.

PMID- 15427332
TI  - Blind nasotracheal intubation.

PMID- 15427333
TI  - Combined anesthesia with sodium pentothal, curare and nitrous oxide; report of
      625 cases.

PMID- 15427334
TI  - The disintegration of procaine solutions.

PMID- 15427335
TI  - Influence of epinephrine and related drugs on toxicity of procaine used
      intravenously in dogs.

PMID- 15427336
TI  - Uranium minerals of India.

PMID- 15427337
TI  - The Cuddapah igneous activity.

PMID- 15427338
TI  - On the scattering of fast electrons.

PMID- 15427339
TI  - Unstable pendant drops in relation to drop-weight method of surface tension.

PMID- 15427340
TI  - A new ultrasonic method for determining elastic constants.

PMID- 15427341
TI  - Chromatographic separation of dyes.

PMID- 15427342
TI  - Variation of dielectric constant with concentration.

PMID- 15427343
TI  - The transpiroscope, a new device.

PMID- 15427344
TI  - Puccinia Kuehnii (Krueg.) Butler on sugarcane in India.

PMID- 15427345
TI  - Necrosis of the mango fruit.

PMID- 15427346
TI  - The effect of boron on the catalase activity of rice plant.

PMID- 15427347
TI  - Studies on the ovaries of Polynemus Tetradactylus Shaw in relation to its
      spawning.

PMID- 15427348
TI  - Addendum to list of chromosome numbers in economic plants.

PMID- 15427349
TI  - A new field host of Microbracon hebetor, S.

PMID- 15427350
TI  - On the occurrence of Glossobalanus parvulus (Punnett) on the Okhamandal
      (Kathiawar) coast.

PMID- 15427352
TI  - Occurrence of green ear stage in sorghum.

PMID- 15427351
TI  - Hybrid maize for the Gokak Canal tract in the state of Bombay.

PMID- 15427353
TI  - Mysore cardamom oil.

PMID- 15427354
TI  - LADY Tata Memorial Trust.

PMID- 15427355
TI  - It's for you to choose.

PMID- 15427356
TI  - Forrester's formula for the determination of calorific value of Indian coals.

PMID- 15427357
TI  - Absorption spectra of thallium halides.

PMID- 15427358
TI  - Micro-fossils from the Bagh beds of Barwaha near Indore.

PMID- 15427359
TI  - On a small collection of plant fossils from Saurashtra.

PMID- 15427360
TI  - B12 content of moldy bran and brood lac extracts.

PMID- 15427361
TI  - Influence of adsorption of FeCy6 and Cd ions, and that of hydrolysis on the
      composition of cadmium ferricyanide.

PMID- 15427362
TI  - Studies in antimalarials; biguanido-arylsulphides and sulphones.

PMID- 15427363
TI  - The influence of manganese on the metabolism of rats and its alleged lipotropic
      activity.

PMID- 15427364
TI  - A rapid method for estimation of leaf area in growing maize plants.

PMID- 15427365
TI  - Studies with methone: part I.

PMID- 15427366
TI  - Studies on local anesthetics: part I.

PMID- 15427367
TI  - Studies on local anesthetics: part II.

PMID- 15427368
TI  - Root development and yield of Lycopersicum esculentum Mill. var. Best of All in
      relation to varying moisture supply.

PMID- 15427369
TI  - Effect of shortening the daily light period in the morning and in the evening, in
      short-day treatment of jute.

PMID- 15427370
TI  - Chromosome diminution in a plant root.

PMID- 15427372
TI  - Integumentary vascular tissue in Cassia tora Linn.

PMID- 15427371
TI  - Half-apocarpy in Carica papaya Linn.

PMID- 15427373
TI  - Chlorozol fast pink, B. K. S., as an anticoagulant in experimental physiology.

PMID- 15427374
TI  - [Inflammability and smoke production of asthma cigarettes].

PMID- 15427375
TI  - [Accepted nomenclature by the Board of the Norwegian Pharmacopeia].

PMID- 15427376
TI  - [Complexones].

PMID- 15427377
TI  - [Studies of acet-4-chloranilide as an impurity in phenacetin].

PMID- 15427378
TI  - [Determination of small amounts of anionic chlorine in phenacetin].

PMID- 15427379
TI  - Stevens-Johnson syndrome with pulmonary involvement.

PMID- 15427380
TI  - Mikulicz's syndrome; report of 2 cases.

PMID- 15427382
TI  - Clinicopathologic case record; epidermoid carcinoma of esophagus with extension
      to pericardium; acute purulent pericarditis.

PMID- 15427381
TI  - Hyponatremia in cardiac failure; a case report.

PMID- 15427383
TI  - An ophthalmology project in Alaska.

PMID- 15427384
TI  - COMMITTEE on Fractures and Other Traumas, American College of Surgeons; the care
      of hand injuries; requirements of early definitive treatment.

PMID- 15427385
TI  - Further observations on cast platinum and baked porcelain restorations.

PMID- 15427386
TI  - The principles of alveolectomy and partial alveolectomy.

PMID- 15427387
TI  - A method of preparing gelfoam and penicillin for surgery.

PMID- 15427388
TI  - An evaluation of fusospirochetosis of the gingivae.

PMID- 15427389
TI  - Individual all-acrylic dentures.

PMID- 15427390
TI  - Consideration of some chemical and physical properties of silicate cements for a
      better understanding of the material.

PMID- 15427391
TI  - President's address.

PMID- 15427392
TI  - Carbohydrate metabolism.

PMID- 15427393
TI  - Functional relationship.

PMID- 15427394
TI  - Another look at dental caries.

PMID- 15427395
TI  - Effect of testicle hormone upon the paradentosis due to dystrophy.

PMID- 15427396
TI  - Mandibular third molar impaction associated with deafness.

PMID- 15427397
TI  - Mechanics of simplified non-traumatic exodontia; principles, technic,
      application.

PMID- 15427398
TI  - OPEN forum on modern anesthesia.

PMID- 15427399
TI  - Hypnodontics or hypnosis in dentistry; history of hypnodontics.

PMID- 15427401
TI  - Orthodontia for the general practitioner of dentistry.

PMID- 15427400
TI  - Tumors of the mouth and jaws.

PMID- 15427402
TI  - Bartholomew Ruspini and his sons.

PMID- 15427403
TI  - Implant dentures.

PMID- 15427404
TI  - A method of injection molding thermoplastics without the use of a monomer or
      copolymer.

PMID- 15427405
TI  - Psychological preparation of the patient for dental anesthesia.

PMID- 15427406
TI  - Hypnodontics or hypnosis in dentistry.

PMID- 15427407
TI  - Tumors of the mouth and jaws.

PMID- 15427408
TI  - The nerve supply to the maxillary bicuspid teeth.

PMID- 15427409
TI  - Local anesthetics.

PMID- 15427410
TI  - Fixation of a mandibular fracture with a Roger Anderson splint.

PMID- 15427411
TI  - OPEN forum on modern anesthesia.

PMID- 15427412
TI  - Orthodontia for the general practitioner of dentistry.

PMID- 15427413
TI  - The influence of E. C. Kirk and Edward H. Angle on Bernard Wolf Weinberger.

PMID- 15427414
TI  - The diagnosis and management of dermatitis resulting from local anesthetics
      employed in dentistry.

PMID- 15427416
TI  - Acrylic dowel crown.

PMID- 15427415
TI  - Psychology in children's department.

PMID- 15427417
TI  - Precision dentures for the general practitioner.

PMID- 15427418
TI  - The problem of extraction in orthodontic therapy; the treatment of the bilateral
      maleruption of canines in the maxillary and mandibular dentures.

PMID- 15427419
TI  - Orthodontia for the general practitioner of dentistry.

PMID- 15427420
TI  - Conservative treatment of cellulitis of left mandible.

PMID- 15427421
TI  - Mechanics of simplified non-traumatic exodontia; principles, technic,
      application.

PMID- 15427422
TI  - Paralysis of the eyelid after a mandibular injection.

PMID- 15427423
TI  - Hypnodontics or hypnosis in dentistry.

PMID- 15427424
TI  - Tumors of the mouth and jaws.

PMID- 15427425
TI  - The hygroscopic expansion technique in dental casting; part 4.

PMID- 15427426
TI  - Some observations on dental conditions in Papua--New Guinea, 1947, with special
      reference to dental caries.

PMID- 15427427
TI  - The treatment of skin tuberculosis with calciferol.

PMID- 15427428
TI  - [Effect of the sebaceous secretion upon alkali resistance of the skin].

PMID- 15427429
TI  - The effect of the iontophoresis of antihistaminics on ultraviolet and grenz ray
      erythema.

PMID- 15427430
TI  - On a peculiar atrophy of the skin in Cushing's syndrome.

PMID- 15427432
TI  - Medical mycology.

PMID- 15427431
TI  - Epidermodysplasia verruciformis.

PMID- 15427433
TI  - [Infections diseases of the skin, with exception of dermatomycosis, tuberculosis
      and leprosy].

PMID- 15427434
TI  - [Clinical aspect of circumscribed pemphigoid scleroderma (morphea bullosa);
      contribution to the problem of its formal pathogenesis].

PMID- 15427435
TI  - [Practical significance of research on the basic principles of infection].

PMID- 15427436
TI  - [Lichen ruber striatus partim acuminatus].

PMID- 15427437
TI  - [Cerebral syphilis with clinical aspect of jacksonian epilepsy].

PMID- 15427438
TI  - [Prevention of nicotine poisoning by filtering tobacco smoke].

PMID- 15427439
TI  - [Use of ethylene glycol in maintaining humidity of smoking tobacco].

PMID- 15427440
TI  - [Seropneumothorax].

PMID- 15427441
TI  - [Parathyroid insufficiency and the eye].

PMID- 15427442
TI  - [Comparative treatment of diphtheria with equine and ovine antitoxins].

PMID- 15427443
TI  - [Intoxication following intravenous injection of dextrose].

PMID- 15427444
TI  - [The need of medical attention in sports].

PMID- 15427445
TI  - [Lieselotte Hermann Children's Hospital, Koserow].

PMID- 15427446
TI  - [Betatron; importance and practical results].

PMID- 15427447
TI  - [Control of tuberculosis].

PMID- 15427448
TI  - [Method for the interruption of pregnancy and announcement of a new instrument].

PMID- 15427449
TI  - [Blood coagulation in myocardial infarct].

PMID- 15427450
TI  - [Novocain treatment of stomach ulcer].

PMID- 15427451
TI  - [Mud bath and the patient].

PMID- 15427452
TI  - [Betatron; importance and practical results].

PMID- 15427453
TI  - [Eye injuries due to delivery by forceps].

PMID- 15427454
TI  - [Method for the interpretation of cytological tests].

PMID- 15427455
TI  - [Medical treatment of multiple sclerosis].

PMID- 15427456
TI  - [Seasonal factors in the manifestation (periodicity) of peptic ulcer].

PMID- 15427457
TI  - [Practical results of music therapy in pedagogics].

PMID- 15427458
TI  - [Growth of children in Leipzig in 3 decades].

PMID- 15427459
TI  - [A year plan in public health, retrospect and outlook].

PMID- 15427460
TI  - [Fresh hormone salve and relation pathology].

PMID- 15427461
TI  - [Investigations on the determination of pentdyopent and mesobiliviolin by means
      of the typical color curve].

PMID- 15427462
TI  - [Significance of Waldeyer's tonsillar ring in the development and therapy of
      tuberculous cervical lymphomas].

PMID- 15427463
TI  - [Treatment of pulmonary tuberculosis with Tb I/698 (conteben)].

PMID- 15427464
TI  - [Brachial neuralgia].

PMID- 15427465
TI  - [Short wave therapy of acute and subacute inflammations of the adnexa].

PMID- 15427466
TI  - [Physics and biology].

PMID- 15427467
TI  - [Objective and subjective determination of blood pressure].

PMID- 15427468
TI  - [Increased frequency of field fever in the Spreewald district].

PMID- 15427470
TI  - [The calling and training of the masseur].

PMID- 15427469
TI  - [Pneumoperitoneum and its indications].

PMID- 15427471
TI  - [6-Sulfanilamido-2,4-dimethylpyrimidine; contribution to sulfonamide therapy].

PMID- 15427472
TI  - [Solanine poisoning after eating potato soup].

PMID- 15427473
TI  - [Dangers of chronic zinc absorption].

PMID- 15427474
TI  - [In commemoration of the seventy-fifth birthday of Cecile Vogt and eightieth of
      Oskar Vogt].

PMID- 15427475
TI  - [Relation between sulfonamide content of blood and urin, and the sulfonamide
      content of the skin and mucous membrane].

PMID- 15427476
TI  - [Objective and subjective determination of blood pressure].

PMID- 15427477
TI  - [Multiple sclerosis and Parainfectious encephalitis].

PMID- 15427478
TI  - [Care following gastrectomy].

PMID- 15427479
TI  - [Pediatric policlinic; observations on the patients of the pediatric policlinic
      of the University of Leipzig].

PMID- 15427480
TI  - [Salicylamide].

PMID- 15427481
TI  - [Clinical observations on poisoning with Agaricus phalloides].

PMID- 15427483
TI  - [History of the blood picture].

PMID- 15427482
TI  - [Early diagnosis of tuberculous spondylitis].

PMID- 15427484
TI  - [Pseudocaverns in children].

PMID- 15427485
TI  - [Supposed injury to the eyes caused by ersatz coffee].

PMID- 15427486
TI  - [New dental curriculum, with purpose of intensive and extensive medical
      development of the profession].

PMID- 15427487
TI  - [Effect of cobalt complexes on catalysis].

PMID- 15427488
TI  - [Sympathectomy in hypertension, and its effect upon gastric function].

PMID- 15427489
TI  - [Electrocardiographic indications of oxygen deficiency in the clinical aspect of
      pulmonary disease].

PMID- 15427490
TI  - [Polamidon addiction].

PMID- 15427491
TI  - [A new chronometer for pregnancy, the term-clock].

PMID- 15427492
TI  - [Hypertrophy of the male breast].

PMID- 15427493
TI  - [Antabus therapy of alcoholism].

PMID- 15427494
TI  - [Preliminary results in the streptomycin therapy of tuberculosis. II].

PMID- 15427495
TI  - [Treatment of accidents due to high tension electric currents].

PMID- 15427496
TI  - [Clinical experiences with curaril].

PMID- 15427497
TI  - [Diseases of the leukopoietic system].

PMID- 15427498
TI  - [Diplomycin, a new antibiotic].

PMID- 15427499
TI  - [Reflex symptoms and hyperalgesic zones in splenic and pancreatic disease].

PMID- 15427500
TI  - [Myocarditis in tuberculosis].

PMID- 15427501
TI  - [Inflammation of the femoral artery].

PMID- 15427502
TI  - [The significance of chronic focal infection in treatment of surgical diseases].

PMID- 15427503
TI  - [Penicillin therapy of scarlet fever].

PMID- 15427504
TI  - [Treatment of whooping cough in infancy with blood transfusion].

PMID- 15427505
TI  - [Peptic ulcer-cure in the practical dietetic therapy of gastric disease].

PMID- 15427506
TI  - [Present status of research and therapy in thromboembolism].

PMID- 15427507
TI  - [Hans Curschmann].

PMID- 15427508
TI  - [Clinical and esthetic views in the diagnosis of skin disease].

PMID- 15427509
TI  - [Rarely observed signs of fatigue in myasthenia gravis pseudoparalytica; origin
      of curare like substances in myasthenia].

PMID- 15427510
TI  - [Problems in peptic ulcer].

PMID- 15427511
TI  - [The 24-hour cycle of the blood platelets].

PMID- 15427512
TI  - [Reflex symptoms and hyperalgesic zones in splenic and pancreatic disease].

PMID- 15427513
TI  - [Metabolic disorders in reactive reticulosis].

PMID- 15427514
TI  - [Chemotherapy of genital tuberculosis in the female].

PMID- 15427515
TI  - [Clinical observations on a new preparation of sulfonated bitumen for
      dermatological use].

PMID- 15427516
TI  - [Chemotherapy of bacterial infections of the intestines].

PMID- 15427517
TI  - [Colchicine poisoning].

PMID- 15427518
TI  - [Appearance of degenerative forms of leukocytes from the reticuloendothelial
      system].

PMID- 15427519
TI  - [A neurological case from Galen's practice].

PMID- 15427520
TI  - [Pre- and postoperative roentgenography in resection of the esophagus].

PMID- 15427521
TI  - [Curare, a significant advance in anesthesia].

PMID- 15427522
TI  - [Thoughts and proposals concerning specialism in anesthesiology].

PMID- 15427523
TI  - [Diagnosis and therapy of Recklinghausen's disease, generalized fibrous
      osteodystrophy].

PMID- 15427524
TI  - [Pre- and postoperative care in major surgery].

PMID- 15427525
TI  - [The patient's reorientation as a prerequisite to favorable and lasting results
      of gastrectomy in peptic ulcer].

PMID- 15427526
TI  - [Endoscopic sympathectomy in angina pectoris].

PMID- 15427527
TI  - [Treatment of Sudeck's syndrome with padutin].

PMID- 15427528
TI  - [Treatment of Erb's progressive muscular dystrophy with resection of the carotid
      sinus nerves].

PMID- 15427529
TI  - [Conteben therapy of tuberculosis of the rectum, and tuberculous fissures and
      fistulas of the anus].

PMID- 15427530
TI  - [Penicillin blood picture of recently available retarded-action preparations].

PMID- 15427531
TI  - [Modern viewpoints in the surgical therapy of chronic disease of the liver and
      bile-ducts].

PMID- 15427532
TI  - [Simple method of resection of the small intestine].

PMID- 15427533
TI  - [Experience with the Zondek-Sulman-Black test for the rapid diagnosis of
      pregnancy].

PMID- 15427534
TI  - [Opacification of the peridural space with 35% visc. per-abrodil M injected
      through the sacral canal, especially for representation of the ileosacral disks].

PMID- 15427535
TI  - [Problems of coronary insufficiency].

PMID- 15427536
TI  - [Results of splenic puncture in diseases of the blood].

PMID- 15427537
TI  - [Investigations on capillary fragility and the effect of rutin therapy].

PMID- 15427538
TI  - [History of syphilitic psychoses].

PMID- 15427539
TI  - [Personal strophanthin therapy and the effect of genins].

PMID- 15427540
TI  - [Internal therapy of the photodermatoses and photogenous diseases].

PMID- 15427541
TI  - [Diagnosis and therapy of virus pneumonia].

PMID- 15427542
TI  - [Epidemiology of epidemic hepatitis].

PMID- 15427543
TI  - [State of milk protein contained in milk-protein-rich powders and medicinal
      preparations; an appeal for verification of the value or worthlessness of milk
      protein admixture].

PMID- 15427544
TI  - [Reimplantation of teeth].

PMID- 15427545
TI  - [Free skin transplantation].

PMID- 15427546
TI  - [Investigations in the physiology and biology of ozone].

PMID- 15427547
TI  - [Preliminary report on a new lingual bar for widening of the mandibular arch].

PMID- 15427548
TI  - [Atrophy of the tongue as manifestation of a vitamin deficiency].

PMID- 15427550
TI  - [Berchtesgaden Conference on focal infection].

PMID- 15427549
TI  - [Bi-crowns].

PMID- 15427552
TI  - [Pathological histology of acute benzine poisoning; primary toxic cerebral
      lipoidosis].

PMID- 15427551
TI  - [Cadaveric blood; pharmacology and enzymatic chemistry of the blood in death due
      to various causes, with special reference to asphyxiation].

PMID- 15427553
TI  - [Pathogenesis of peroral trichloroethylene poisoning].

PMID- 15427554
TI  - [Poisoning by barium carbonate mistaken for baking powder].

PMID- 15427555
TI  - [Vacuolar cardiac degeneration in methyl alcohol poisoning].

PMID- 15427556
TI  - [Dangers of careless handling of chlorate salts].

PMID- 15427557
TI  - [Fatal physostigmine poisoning].

PMID- 15427558
TI  - [Effect of tincture of iodine medication of numerous superficial wounds upon the
      alcohol picture of the blood].

PMID- 15427559
TI  - [Distention ruptures of the stomach in acute gastric volvulus].

PMID- 15427560
TI  - [A new agglutinable erythrocyte property, the S factor].

PMID- 15427561
TI  - [Determination of aloe in urine and feces].

PMID- 15427562
TI  - [Diaplacental values of ether in obstetrical anesthesia].

PMID- 15427563
TI  - Ambulatory shock therapy; a 10 year survey.

PMID- 15427564
TI  - Selection of patients for a teaching hospital and effect of resident training.

PMID- 15427565
TI  - Brain tumors in mental patients; a statistical study.

PMID- 15427566
TI  - Evaluation of psychobiological integration by mirror drawing.

PMID- 15427567
TI  - NEUROLOGICAL clinical pathological conference; Addison's disease (neurological
      signs produced by hypoglycemia).

PMID- 15427568
TI  - Fundamentals of psychosomatics in relation to therapy.

PMID- 15427569
TI  - Periodic relapsing catatonia.

PMID- 15427570
TI  - IN HONOREM Karl Wessely.

PMID- 15427571
TI  - PUBLICATIONS of Karl Wessely.

PMID- 15427572
TI  - Quanta explantation of vision.

PMID- 15427573
TI  - Visual purple.

PMID- 15427574
TI  - Recent studies of lighting and vision.

PMID- 15427575
TI  - Twin research in ophthalmology.

PMID- 15427576
TI  - Ophthalmic aspects of protein deficiency and disordered protein metabolism.

PMID- 15427577
TI  - Some aspects of ocular pharmacology.

PMID- 15427578
TI  - Protective glasses for welding.

PMID- 15427579
TI  - Modern refinements in tonometry.

PMID- 15427580
TI  - [Indications for therapeutic abortion in rural hospitals].

PMID- 15427581
TI  - [Sulfa preparations as a cause of periarteritis nodosa].

PMID- 15427582
TI  - [Streptomycin therapy of pulmonary tuberculosis at the Kontioniemen sanatorium].

PMID- 15427583
TI  - [Congenital and acquired syphilis in Finnish children].

PMID- 15427584
TI  - [3 cases of amenorrhea due to granulosa cell tumor].

PMID- 15427586
TI  - [Statistics on completed and interrupted treatment of syphilis at municipal
      clinics in Helsinki, 1944-47].

PMID- 15427585
TI  - [Classification of the singing voice].

PMID- 15427587
TI  - [Modern methods in diagnosis of pregnancy; observations made in the United
      States].

PMID- 15427588
TI  - Aureomycin in tick typhus; a note of its use in four cases.

PMID- 15427589
TI  - Non-specific mesenteric adenitis.

PMID- 15427590
TI  - The sickle cell trait among the Zande tribe of the southern Sudan.

PMID- 15427591
TI  - A case of massive subcapsular haematoma of the spleen.

PMID- 15427592
TI  - Two cases of hydrophobia.

PMID- 15427593
TI  - Skin grafting in the treatment of tropical ulcer.

PMID- 15427594
TI  - A case of relapsing fever in a child of nine days old.

PMID- 15427595
TI  - Trachoma; the substance of a clinical address at Mulago Hospital.

PMID- 15427596
TI  - Red blood count of East African students.

PMID- 15427597
TI  - Argas brumpti Neumann 1907 (Argasidae, Ixodoidea) in Kenya Colony.

PMID- 15427598
TI  - Penicillin in the treatment of a case of pelvic actinomycosis.

PMID- 15427599
TI  - [Technic of transorbital leucotomy].

PMID- 15427600
TI  - [Late and very late post-brucellosis epilepsy].

PMID- 15427601
TI  - [Two cases of phagomania].

PMID- 15427602
TI  - [Asymmetry of cerebellar tests in normal subjects].

PMID- 15427603
TI  - [The study of Abderhalden's protective ferments during the past decade].

PMID- 15427604
TI  - [The Hashishin Club].

PMID- 15427605
TI  - [The genetic point of view].

PMID- 15427606
TI  - [The child's thoughts and the formulation of perceptions in the Rorschach test].

PMID- 15427607
TI  - [The awakening of social feeling in the nursery].

PMID- 15427608
TI  - [Fragmentary perception of social and moral concepts in the child].

PMID- 15427609
TI  - [Attempted objective study of the esthetic sense in the child].

PMID- 15427610
TI  - [Child psychology in German displaced persons camps].

PMID- 15427611
TI  - [Psychosomatic perspective in the child].

PMID- 15427612
TI  - [Behaviorism and neuropsychiatry].

PMID- 15427614
TI  - [Remote sequels of war emotions].

PMID- 15427613
TI  - [Reality and the functions of the unreal (the third world)].

PMID- 15427615
TI  - [Biological structures and behavior; fundamental elements of a biological concept
      of psychiatry].

PMID- 15427616
TI  - Compounds of quinone structure as allergens and cancerogenic agents.

PMID- 15427617
TI  - [Paleo-neurology at the beginning of a new phase].

PMID- 15427618
TI  - Mechanism of the photo-condensation of steroids.

PMID- 15427619
TI  - [Preparation of four-ring ketones from tricyclic ketone of Koster and Logemann].

PMID- 15427620
TI  - [Isolation of neon isotope Ne20 of 99.95% isotopic purity in a thermal diffusion
      column].

PMID- 15427621
TI  - [Measurement of magnetic susceptibility of vitamin B12].

PMID- 15427622
TI  - [Action of carbon monoxide on respiration and absorption of wheat roots].

PMID- 15427623
TI  - [Direct measurement of the great period of growth of the successive cells of the
      growth zone of a root].

PMID- 15427624
TI  - X-ray diffraction and x-ray absorption studies of immobilized bones.

PMID- 15427625
TI  - [Extractible proteins of the striated muscle after treatment of the pulp with
      certain organic solvents].

PMID- 15427626
TI  - [Contribution to the analysis of the post-mortem condition of the cochlear
      potential].

PMID- 15427627
TI  - [Influence of pH of the cerebrospinal fluid on respiration].

PMID- 15427628
TI  - [Histaminic desensitization in guinea pig and rat].

PMID- 15427629
TI  - [Fatty degeneration of the organism in chronic gamma-hexachlorocyclohexane
      poisoning in a dog].

PMID- 15427630
TI  - [Modification of the Van Slyke-Cullen aeration assembly and its adaptation to the
      micro determination of protein nitrogen after Kjeldahl digestion and cold
      treatment of ammonia].

PMID- 15427631
TI  - [Modification of the Conway cell for determination of microdiffusion].

PMID- 15427632
TI  - [Normal perspective, its discovery in the 15th century].

PMID- 15427633
TI  - In honor of Bruno Kisch.

PMID- 15427634
TI  - The endocrinological basis of the Beard test for malignancy.

PMID- 15427635
TI  - Fertility and sterility by ions actions.

PMID- 15427636
TI  - Some studies on basic amines in the blood under physiologic and pathologic
      conditions.

PMID- 15427637
TI  - The effect of x-rays on the milk coagulating activity of papain.

PMID- 15427638
TI  - The fluorescence of adrenaline and adrenochrome.

PMID- 15427639
TI  - [Significance of blood platelets in hemostasis and extravasation in normal and
      pathologic states].

PMID- 15427640
TI  - Biological characteristics of melanin granules in the normal choroid and in
      malignant melanomas.

PMID- 15427641
TI  - A simple technique for measuring the growth of mouse mammary tumors.

PMID- 15427642
TI  - Eradication of spontaneous mouse tumors by high frequency radiation. I.
      Biological part.

PMID- 15427643
TI  - Retardation of the growth of mouse tumors by d-amino acid therapy.

PMID- 15427644
TI  - The U wave in the chest leads.

PMID- 15427645
TI  - Etiology and therapy of arteriosclerosis.

PMID- 15427646
TI  - Further attempts in electro microscopy.

PMID- 15427647
TI  - [Reduction by copper in the presence of ammonium cyanide and ammoniac].

PMID- 15427648
TI  - Differential diagnosis of ventricular paroxysmal tachycardia.

PMID- 15427649
TI  - A slide for the direct determination of the corrected relative Q-T duration,
      heart rate, and percent-amplitudes of electrocardiographic deflections.

PMID- 15427650
TI  - On the effect of amino acids on a color reaction of aromatic amidines.

PMID- 15427651
TI  - Attempts at clinical measurement of pulmonary arterial pressure.

PMID- 15427652
TI  - The neuromotor mechanism of the small blood vessels in membranes of the frog
      (Rana pipiens) and the hamster (Mesocricetus auratus) with reference to the
      normal and pathological conditions of blood flow.

PMID- 15427653
TI  - Remarks upon present-day electrocardiographic theory.

PMID- 15427654
TI  - Differentiation of free and bound tryptophane; note on tryptamine.

PMID- 15427655
TI  - Deproteinization with perchloric acid.

PMID- 15427656
TI  - Sulphatase in dental caries.

PMID- 15427657
TI  - [Effect of pilocarpine upon the heart in the isolated atropinized heart and
      lung].

PMID- 15427658
TI  - Pressor and cardiac effects of adrenochrome (omega) in the atropinized cat.

PMID- 15427659
TI  - The effect of trimeton maleate on pathogenic fungi.

PMID- 15427660
TI  - Studies on the fate of curare in the rabbit.

PMID- 15427661
TI  - The mechanism of recovery of the guinea pig gut from inhibition by atropine and
      anti-histaminics.

PMID- 15427662
TI  - Quantitative determination of stilbamidine and 2-hydroxystilbamidine in urine and
      tissue.

PMID- 15427663
TI  - Fluorine and vitamin B.

PMID- 15427664
TI  - [Goethe's theories on color, a legacy].

PMID- 15427665
TI  - Demonstration in vitro of a humoral heat regulation mechanism.

PMID- 15427666
TI  - Hemolytic reaction caused by massive transfusion of incompatible blood, treated
      successfully by exchange transfusion.

PMID- 15427667
TI  - The problem of functional coronary collaterals.

PMID- 15427668
TI  - Fat metabolism in Alaskan eskimos.

PMID- 15427669
TI  - The influence of urea and hydrotropic ions on the resolubility of albumin dried
      from the solved state.

PMID- 15427670
TI  - An apparent associating effect of protein dissociating denaturants.

PMID- 15427671
TI  - Studies on the sacral reflex arc in paraplegia; clinical observations on
      inhibitory impulses within the sacral reflex arc.

PMID- 15427672
TI  - An analysis of hearing loss patterns in a rural Illinois school system; general
      considerations.

PMID- 15427673
TI  - Common dermatose; of the ear.

PMID- 15427674
TI  - Allergic otitis media.

PMID- 15427675
TI  - The fenestration operation; indications, technique and results; analysis of 214
      operations.

PMID- 15427676
TI  - Rehabilitation of the deafened.

PMID- 15427677
TI  - [Plan for the new pharmacopeia in Yugoslavia].

PMID- 15427678
TI  - [Application of biologic methods in pharmacognosy].

PMID- 15427679
TI  - [New cyanide preparations].

PMID- 15427680
TI  - [Pharmacology in Yugoslavia; historic note].

PMID- 15427681
TI  - [Liquidation and control of infectious diseases, the primary objective of all
      medical personnel].

PMID- 15427682
TI  - [Trauma in obstetrics].

PMID- 15427683
TI  - [Dysentery in infants and children].

PMID- 15427684
TI  - [Angina phlegmonosa].

PMID- 15427685
TI  - [Foreign bodies in the upper respiratory tract; clinical aspects and treatment].

PMID- 15427686
TI  - [Cancer of the skin and its control].

PMID- 15427687
TI  - [Role of feldshers in the new plan of sanitation and control of epidemics].

PMID- 15427688
TI  - [Role of the feldsher in the regional sanitary-epidemiologic post].

PMID- 15427689
TI  - [New raise in medical sciences in the Soviet Union].

PMID- 15427690
TI  - [Aleksandr Alekseevich Bobrov, 30.V.1850-26.IX.1904].

PMID- 15427691
TI  - [Importance of proper ventilation in schools and children institutions].

PMID- 15427692
TI  - [Certain useful but not well known methods in bandaging].

PMID- 15427693
TI  - [Shostakovskii's balsam].

PMID- 15427694
TI  - [Subjectivity and objectivity in psychiatric thought].

PMID- 15427695
TI  - [Food supply in Nova Iguacu, Rio de Janeiro].

PMID- 15427696
TI  - [Early diagnosis of gynecological cancer].

PMID- 15427697
TI  - [Psychiatric social service in industry].

PMID- 15427698
TI  - [Vitamin K, a new therapeutic for whooping cough].

PMID- 15427699
TI  - [Conservative surgery in gynecology].

PMID- 15427700
TI  - [Vital Brasil].

PMID- 15427701
TI  - [Organization of social medicine in Brazil].

PMID- 15427702
TI  - Vitamin content of citrus products.

PMID- 15427703
TI  - Changes in metabolic characteristics of white potato as affected by conditions of
      storage.

PMID- 15427704
TI  - Use and properties of non-fat dry milk solids in food preparation. I. Effect on
      viscosity and gel strength.

PMID- 15427705
TI  - Influence of cooking method on ascorbic acid and thiamine contents of four
      varieties of kale (Brassica oleracea v. acephala).

PMID- 15427706
TI  - Effect of single and repeated doses of gossypol on the rat.

PMID- 15427707
TI  - Effect of thawing and cooking methods on palatability and nutritive value of
      frozen ground meat. I. Pork.

PMID- 15427708
TI  - Effect of thawing and cooking methods on palatability and nutritive value of
      frozen ground meat. II. Beef.

PMID- 15427709
TI  - Effect of thawing and cooking methods on palatability and nutritive value of
      frozen ground meat. III. Lamb.

PMID- 15427710
TI  - [Some present day problems of whooping cough].

PMID- 15427711
TI  - [Syphilis in pediatrics].

PMID- 15427712
TI  - [How to treat congenital syphilis].

PMID- 15427713
TI  - [Infantile acrodynia].

PMID- 15427714
TI  - [Toxicosis of infants].

PMID- 15427715
TI  - [Bronchial dilatation in the child].

PMID- 15427716
TI  - [Speech disorders in the child].

PMID- 15427717
TI  - [Cat scratch disease].

PMID- 15427718
TI  - [Vitamins and digestive disorders].

PMID- 15427719
TI  - [Problem which arise in the streptomycin treatment of tuberculous meningitis in
      the adult].

PMID- 15427720
TI  - [Blood proteins and surgery].

PMID- 15427721
TI  - [Acute jaundice].

PMID- 15427722
TI  - [Kaolinated pectin in the treatment of ulcers].

PMID- 15427723
TI  - [Persistance of the ductus arteriosus].

PMID- 15427725
TI  - [Therapeutic indications in parkinsonism].

PMID- 15427724
TI  - [Tuberculous meningitis; anatomic problems and neurosurgical attempts].

PMID- 15427726
TI  - [Arterial angiomas of the brain].

PMID- 15427727
TI  - [Human toxoplasmosis].

PMID- 15427728
TI  - [Pulmonary atelectasis].

PMID- 15427729
TI  - [Contribution to the study of proteinemia, hemocrit value and hemoglobinemia by
      the gravimetric method with copper sulfate" b) in obstetrics].

PMID- 15427730
TI  - [Glycocoll and anginoid state].

PMID- 15427731
TI  - [Immediate and remote results of temporary suspension of the adnexa according to
      the method of Revoltella].

PMID- 15427732
TI  - [Anesthetic block and resection of the preaortic plexus in the therapy of angina
      pectoris].

PMID- 15427733
TI  - [Para-aminobenzoic acid in the therapy of acute articular rheumatism].

PMID- 15427734
TI  - [Distribution and frequency of various blood diseases in Friuli].

PMID- 15427735
TI  - [A specific epididymitis].

PMID- 15427736
TI  - [Appendicitis; clinical findings and statistics].

PMID- 15427737
TI  - [Stratigraphy in the study and treatment of ulcero-cavitary tuberculosis of the
      lung].

PMID- 15427738
TI  - [Chemotherapy of acute peritoneal infections as a complement to emergency
      surgery].

PMID- 15427739
TI  - [Spontaneous rupture of the aorta].

PMID- 15427740
TI  - [Superstitions of medical interest in Livy].

PMID- 15427742
TI  - A cancer-finding team.

PMID- 15427741
TI  - [Tuberculosis of the parotid gland].

PMID- 15427743
TI  - The problem of obscure fever.

PMID- 15427744
TI  - Troubles in the thorax and abdomen.

PMID- 15427745
TI  - The doctor's bag--what should be in it.

PMID- 15427746
TI  - Office pinch grafting.

PMID- 15427747
TI  - Pernicious anemia discussion of treatment with special reference to vitamin B12.

PMID- 15427748
TI  - The importance of medical economics.

PMID- 15427749
TI  - So you want to be an animal photographer?

PMID- 15427750
TI  - What is new in proctology.

PMID- 15427751
TI  - Objectives in diabetes.

PMID- 15427752
TI  - Cervical disk protrusion.

PMID- 15427753
TI  - Brief survey of arteriosclerosis.

PMID- 15427755
TI  - Arterial hypertension.

PMID- 15427754
TI  - Obligations in anesthesia.

PMID- 15427756
TI  - Integration of the general practitioners into well-organized private group
      practice clinics.

PMID- 15427757
TI  - A rose by any other name.

PMID- 15427758
TI  - Cancer of the gastrointestinal tract.

PMID- 15427759
TI  - Quinidine in heart disease.

PMID- 15427760
TI  - Cortisone and rheumatoid arthritis.

PMID- 15427761
TI  - Sterility-diagnosis and management.

PMID- 15427762
TI  - Acute appendicitis with perforation.

PMID- 15427763
TI  - The management of ulcerative colitis.

PMID- 15427764
TI  - Medicine and the Hoover Report.

PMID- 15427765
TI  - Report of the Chairman of Board of Directors, St. Louis, Missouri, February,
      1950.

PMID- 15427766
TI  - REPORT on internships and residency training for general practice.

PMID- 15427767
TI  - [Not Available].

PMID- 15427768
TI  - [Anatomo-clinical study of cancerous degeneration in peptic ulcer].

PMID- 15427769
TI  - [Severe diverticulosis of the jejunum as partial cause of the sprue syndrome].

PMID- 15427770
TI  - Clinical observations on the severity of liver failure in portal cirrhosis.

PMID- 15427771
TI  - Amyotrophic lateral sclerosis observed in 5 persons after gastric resection.

PMID- 15427772
TI  - Cysts of the esophagus; case report and review of literature.

PMID- 15427773
TI  - X-ray treatment for peptic ulcer does not appear to damage the heart.

PMID- 15427774
TI  - Gastritis of the postoperative stomach: enterogastrone therapy.

PMID- 15427775
TI  - Clinical evaluation of orally administered hog duodenal substance in the
      treatment of chronic ulcerative colitis.

PMID- 15427776
TI  - The relation of the regenerated liver nodule to the vascular bed in cirrhosis.

PMID- 15427777
TI  - Dissociation of secretion of pancreatic enzymes and bicarbonate in patients with
      chronic pancreatitis.

PMID- 15427778
TI  - Measurement of serum cholinesterase activity in the study of diseases of the
      liver and biliary system.

PMID- 15427779
TI  - The effect of colonic distention on the white blood cell picture.

PMID- 15427780
TI  - Gastric secretion and motility after vagotomy in dogs.

PMID- 15427781
TI  - The relationship of potassium to the electrolytes and to the proteins of the
      gastric juice of man; effect of persistent loss of gastric juice on serum
      potassium.

PMID- 15427782
TI  - Multiple-balloon-kymograph recording of variations in motility of the upper small
      intestine in man during long observation periods before and after placebo
      administration.

PMID- 15427783
TI  - Pedunculated papilloma of stomach.

PMID- 15427784
TI  - Surgical stricture of the common bile duct followed by biliary cirrhosis and
      portal hypertension; a case report.

PMID- 15427785
TI  - Pneumoperitoneum following gastroscopy with spontaneous recovery; report of a
      case.

PMID- 15427786
TI  - Whipple's disease (lipophagia granulomatosis); report of 1 case.

PMID- 15427787
TI  - Diffuse adenomatous (hereditary) polyposis; report of a case in which polyps
      appeared six years after onset of ulcerative colitis.

PMID- 15427788
TI  - Criteria for histamine achlorhydria.

PMID- 15427789
TI  - Histamine dosage.

PMID- 15427790
TI  - [Present day orientation of modern therapeutics].

PMID- 15427791
TI  - [Treatment of acute and subacute articular rheumatism in the adult].

PMID- 15427792
TI  - [Treatment of polyarthritis with suprarenal hormone: cortisone and a pituitary
      hormone, corticotropin].

PMID- 15427793
TI  - [Indications for surgical treatment of sciatica].

PMID- 15427794
TI  - [Synthetic estrogens in rheumatism therapy].

PMID- 15427795
TI  - [Rheumatism and vitamin therapy].

PMID- 15427796
TI  - [Treatment of hydrarthrosis].

PMID- 15427797
TI  - [Rheumatism and hyaluronidase].

PMID- 15427798
TI  - [Hormonal and pharmacodynamic treatment of hormono-genital disorders in women].

PMID- 15427799
TI  - [Salicylate and vitamin therapy in chronic rheumatism].

PMID- 15427800
TI  - [A new salicylate derivative, succinyl-disalicylic acid].

PMID- 15427801
TI  - [The automobile and health].

PMID- 15427802
TI  - [How must one treat primo-secondary syphilis?].

PMID- 15427803
TI  - [Disadvantages of penicillin-bismuth treatment of syphilis].

PMID- 15427804
TI  - [Late focal lesions of acquired congenital syphilis: conclusions on the
      transmission of syphilis by blood transfusion].

PMID- 15427805
TI  - [Diagnosis and treatment of acute eczema of the face].

PMID- 15427806
TI  - [Sulfur therapy of acne; penetrating sulfur].

PMID- 15427807
TI  - [Dermato-syphilography].

PMID- 15427809
TI  - [Social security in the United States].

PMID- 15427808
TI  - [Hormonal and pharmacodynamic treatment of hormono-genital disorders in women].

PMID- 15427810
TI  - [Responsibility for professional errors in a public hospital].

PMID- 15427811
TI  - [Therapeutic acidity in dermatology].

PMID- 15427812
TI  - [Pseudo-surgical back pain of psychic origin; pathogenic and therapeutic
      problems].

PMID- 15427814
TI  - [Primary atypical pneumonia].

PMID- 15427813
TI  - [Biologic and therapeutic considerations of vitamin B 12].

PMID- 15427815
TI  - [Plummer-Vinson syndrome].

PMID- 15427816
TI  - [Bacillus subtilis in intestinal therapy].

PMID- 15427817
TI  - [Hormonal and pharmacodynamic treatment of female hormono-genital disorders].

PMID- 15427818
TI  - [The association of sodium salicylate and vitamin B1 in rheumatism therapy].

PMID- 15427819
TI  - [Treatment of diabetic coma].

PMID- 15427820
TI  - [Diabetic arteritis].

PMID- 15427821
TI  - [Surgical treatment of diabetes mellitus].

PMID- 15427822
TI  - [Indications for gonadotropic hormones, testosterone and androgens in man].

PMID- 15427823
TI  - [Classification, diagnosis and treatment of anemias].

PMID- 15427824
TI  - [Treatment of myeloid leukemias].

PMID- 15427825
TI  - [Infectious lymphocytosis].

PMID- 15427826
TI  - [Some clinical aspects of acute leukemias and their treatment].

PMID- 15427828
TI  - [Is yellow fever conquered?].

PMID- 15427827
TI  - [Recent ideas on the physiology of serum iron].

PMID- 15427829
TI  - [Modern medicaments and treatment of human trypanosomiasis].

PMID- 15427830
TI  - [Tropical sprue].

PMID- 15427831
TI  - [Tropical diseases].

PMID- 15427832
TI  - [Treatment of labor hemorrhages].

PMID- 15427833
TI  - [Kempner's rice diet for arterial hypertension].

PMID- 15427834
TI  - [Pains of tabes dorsalis].

PMID- 15427835
TI  - The cytogenetic effect of slow neutrons.

PMID- 15427836
TI  - The genetic basis of heterosis in maize.

PMID- 15427837
TI  - Chromosome segregation in translocations involving chromosome 6 in maize.

PMID- 15427839
TI  - [The finances and the accounts of social service institutions].

PMID- 15427838
TI  - Self-incompatibility studies in guayule; inheritance.

PMID- 15427840
TI  - [Report on the proceedings of the Second International Congress on Iatro- and
      Orthopedagogics, held at Amsterdam, 18-22 July 1949].

PMID- 15427841
TI  - [Overwork at school; a statement by the Swiss Commission of School Physicians].

PMID- 15427842
TI  - [Greater incidence of goiter in Germany].

PMID- 15427843
TI  - [Annual report for 1949 of the Zurich Central Office for Marriage and Sex
      Counsel].

PMID- 15427844
TI  - [Annual report for 1949 of the Basel Society for Hygiene].

PMID- 15427845
TI  - [Medium and variability of microorganisms].

PMID- 15427846
TI  - [Organization of sanitary zones to protect water supply sources].

PMID- 15427847
TI  - [The plan to improve sanitary conditions and housing in regions of Uzbekistan].

PMID- 15427848
TI  - [Mine dumping places as a cause of sulfur dioxide pollution of air].

PMID- 15427849
TI  - [Study of sanitary-hygienic conditions of workers in foundries; effect of tar
      fumes in electric generators].

PMID- 15427850
TI  - [Results of the commission of the Academy of Sciences in the control of
      silicosis].

PMID- 15427851
TI  - [The role of dysentery bacteria in toxic food infection].

PMID- 15427852
TI  - [New hygiene program for medical and pediatric institutes].

PMID- 15427853
TI  - [N. I. Teziakov, 1859-1925].

PMID- 15427854
TI  - [Determination of fat content prepared meals by Gerber's acidless method].

PMID- 15427855
TI  - [The method of sealing milk bottles].

PMID- 15427856
TI  - [Toxicity of Galeopsis speciosa].

PMID- 15427857
TI  - [Cranberry as a medium for speedy detachment of nits from the hair].

PMID- 15427858
TI  - [Organization of fly control in the plan of sanitation of cities].

PMID- 15427859
TI  - [Synthetic organic insecticide DDT].

PMID- 15427860
TI  - [Sulfur and glycemia].

PMID- 15427861
TI  - [Quantitative determination of the formed elements in urinary sediment].

PMID- 15427862
TI  - [Antitubercular action of derivatives of hydrazothiocarbonamide. I. Research on
      hydrazothiocarbonamide of phenylsulfonamide].

PMID- 15427863
TI  - [Hypoglycemic action of alpha-tocopherol in relation to the method of
      administration (oral, parenteral, endovenous); clinico-experimental research].

PMID- 15427864
TI  - [Variations of the oscillometric index by endoarterial administration of
      vasoactive substances].

PMID- 15427865
TI  - [Jacobaeus operation; contributions of 125 personal interventions].

PMID- 15427866
TI  - [Stratigraphy of the bicosto-clavicular region].

PMID- 15427867
TI  - [Mechanism of the action of myanesin on the striate muscles].

PMID- 15427868
TI  - [Painful subcutaneous syndrome; panniculitis; cellulitis; fibrositis; synthetic
      critical review].

PMID- 15427869
TI  - [Toxoplasma and toxoplasmosis].

PMID- 15427870
TI  - [Late complication of renal decapsulation].

PMID- 15427871
TI  - [Histopathological observations on the means of spreading of epithelioma of the
      penis along the corpora cavernosa].

PMID- 15427872
TI  - [The fluorescein test in ischemic syndromes of the extremities].

PMID- 15427873
TI  - [Notes on the technic of laparotomy].

PMID- 15427874
TI  - [Reconstruction of the continuity of the digestive tract following total
      gastrectomy by means of a segment of the transverse colon].

PMID- 15427875
TI  - [Cardioangiography and pneumodensography in the diagnosis of tumors of the
      thorax].

PMID- 15427876
TI  - [Action of procaine (novocaine) in experimental shock].

PMID- 15427877
TI  - [Neurinoma of the vagus in a right latero-cervical site].

PMID- 15427878
TI  - [Histological changes in the tunica vaginalis testis following resection and
      eversion; experimental contribution].

PMID- 15427879
TI  - [Experimental research in vascular surgery; technic of termino-terminal
      anastomosis].

PMID- 15427880
TI  - [A new type of anesthesia chart].

PMID- 15427881
TI  - [Infra-red photography in medical research; present state and future prospects].

PMID- 15427882
TI  - [Ileo-terminal adhesions in chronic pseudoappendicitis].

PMID- 15427883
TI  - [Mortality in gastric resections for ulcer].

PMID- 15427884
TI  - [Variations in the virulence of E. coli in relation to sensitivity to certain
      antibiotics].

PMID- 15427885
TI  - [Antibiotics and sulfonamides in the treatment of acute appendicular peritonitis;
      experimental study on the efficacy of penicillin, streptomycin and sulfaguanidine
      in acute peritonitis produced by the Bower method].

PMID- 15427886
TI  - [Vascularization of the parathyroids].

PMID- 15427887
TI  - [Experimental research in vascular surgery; methods of operating on the aorta
      without complete interruption of the circulation].

PMID- 15427888
TI  - [Cancerous exstrophy of the bladder].

PMID- 15427889
TI  - [Technic of the surgical treatment of inguinal hernia].

PMID- 15427890
TI  - [Support for aspirator tube and diathermy cable].

PMID- 15427891
TI  - [Acute ulcerous aneurysm of the heart].

PMID- 15427892
TI  - [Penicillin, obstacle to the bacteriological verification of diphtheria].

PMID- 15427893
TI  - [Results of radiotherapy of cancer of the lip].

PMID- 15427894
TI  - [Use of a bismuth salt in the therapy of intestinal amebiasis].

PMID- 15427895
TI  - [Notes and observations on the legal criteria which regulate the admission of
      patients into hospitals].

PMID- 15427896
TI  - Injuries of the semilunar cartilages in miners: a review of 200 cases, with
      special reference to the post-operative disability time.

PMID- 15427897
TI  - Cystic mucoid degeneration of the aortic media with spontaneous rupture of the
      aorta.

PMID- 15427898
TI  - The relation of hypertension to the renal circulation.

PMID- 15427899
TI  - Portrait of a surgeon.

PMID- 15427900
TI  - The care of children.

PMID- 15427901
TI  - America re-visited.

PMID- 15427902
TI  - Natural history of certain viral infections of the liver.

PMID- 15427903
TI  - The mixture as before.

PMID- 15427904
TI  - The natural history of influenza.

PMID- 15427905
TI  - [What do involutional hemorrhages mean from the endocrine point of view? Study of
      vaginal smears with endometrial biopsies].

PMID- 15427907
TI  - [Azoospermia and sterility; statistical study of 100 cases of azoospermia].

PMID- 15427906
TI  - [Dyspareunia from vulvovaginal stenosis; treatment by fixation in the perineum of
      a flap of vaginal mucosa].

PMID- 15427908
TI  - [Pathogenesis of eclampsia; therapeutic deductions].

PMID- 15427909
TI  - [Endocrine glands of the female ovary; their variability; their variations
      according to personal morphological observations].

PMID- 15427910
TI  - [Enterovaginal fistulas; applications of the method of transanal reduction or the
      Hogenegg-Kocher method].

PMID- 15427911
TI  - [Chorioepithelioma with paradoxic pregnancy test after hydatiform mole].

PMID- 15427912
TI  - [Pelvis with horizontal symphysis].

PMID- 15427913
TI  - [Stopping of lactation by estrogens. I. Stopping of lactation by dienestrol by
      oral administration].

PMID- 15427914
TI  - [Ambulatory treatment of simple vomiting of pregnancy by intravenous novocain].

PMID- 15427915
TI  - [Menstrual reactivation of the uterus 37 1/2 years after menopause].

PMID- 15427916
TI  - [The relative importance of sterility factors].

PMID- 15427917
TI  - [Functional uterine hemorrhages].

PMID- 15427919
TI  - [Ovarian autografts].

PMID- 15427918
TI  - [Hyperhormonal obesity in women].

PMID- 15427920
TI  - [Hysterosalpingography; normal uterus and permeable tubes].

PMID- 15427921
TI  - [Fibroma or ovarian cyst?].

PMID- 15427922
TI  - [Technic and interpretation of endometrial biopsies during the menstrual cycle].

PMID- 15427923
TI  - [French balneology in gynecology].

PMID- 15427924
TI  - [Vaginitis].

PMID- 15427925
TI  - Bacteriological examinations of water cisterns in Jerusalem; coliform
      microorganisms isolated from cistern water (in Hebrew; English summary).

PMID- 15427926
TI  - Functional hyperhormonal cysts of the ovary. (in Hebrew; English summary).

PMID- 15427927
TI  - The surgical treatment of stress-incontinence of urine. (in Hebrew; English
      summary).

PMID- 15427928
TI  - The use of scopanin in obstetrics. (in Hebrew; English summary).

PMID- 15427929
TI  - The treatment of necrotic myomata with ultra short waves. (in Hebrew; English
      summary).

PMID- 15427930
TI  - Tuberculous salpingitis treated surgically. (in Hebrew; English summary).

PMID- 15427931
TI  - Androgens in treatment of female sterility. (in Hebrew; English summary).

PMID- 15427932
TI  - Outbreak of poliomyelitis in Israel, 1949-1950; epidemiological aspects. (in
      Hebrew; English summary).

PMID- 15427933
TI  - Modern aspect of pathological phenomena in man; contribution to the etiology of
      the acute non-specific uremia. (in Hebrew; English summary).

PMID- 15427934
TI  - Experiences with retropubic prostatectomy (in Hebrew; English summary).

PMID- 15427935
TI  - An unusual wound of the uterus (in Hebrew; English summary).

PMID- 15427936
TI  - About the problem of hereditary idiopathic tremor (in Hebrew; English summary).

PMID- 15427937
TI  - Problems in gastroduodenal surgery with special reference to ulcer; clinical and
      experimental observations.

PMID- 15427938
TI  - Cervical atresia complicating parturition; report of a case.

PMID- 15427939
TI  - Skeletal tumours and treatment.

PMID- 15427940
TI  - Trichloracetic acid in the management of rhinophyma.

PMID- 15427941
TI  - Incomplete abortion; an evaluation of diagnosis and treatment of 727 consecutive
      cases of incomplete abortions.

PMID- 15427942
TI  - Recent advances in surgical care.

PMID- 15427943
TI  - Leiomyoma of the jejunum associated with Von Recklinghausen's disease; case
      report.

PMID- 15427944
TI  - Highlights, 1950 Annual Meeting American College of Physicians.

PMID- 15427945
TI  - Kidney tumors: a 10 year survey.

PMID- 15427946
TI  - The role of vitamin therapy in chronic ulcerative colitis; a case report.

PMID- 15427947
TI  - Medical aspects of atomic warfare.

PMID- 15427948
TI  - Acute pancreatitis.

PMID- 15427949
TI  - The Hawaii Medical Service Association.

PMID- 15427950
TI  - A lost art in obstetrics.

PMID- 15427951
TI  - The more common blood dyscrasias seen in general practice.

PMID- 15427952
TI  - [Attempt at classification and diagnosis of cranial depressions].

PMID- 15427953
TI  - [Anatomy and topography of the lumbar sympathetic nerve].

PMID- 15427954
TI  - [Simple operation for floating kidney].

PMID- 15427955
TI  - [Ganglion].

PMID- 15427956
TI  - [Spontaneous hemopneumothorax and its indication for thoracotomy].

PMID- 15427957
TI  - [Metabometer; portable apparatus for determination of basal metabolic rate].

PMID- 15427958
TI  - [Observations and study of a little known form of occupational chromium
      poisoning].

PMID- 15427959
TI  - [Circulation velocity, determined by means of the intracardiac catheter].

PMID- 15427960
TI  - [On the pharmacological effect upon the cerebral vessels in man].

PMID- 15427961
TI  - [Recent data on the pathogenesis of poliomyelitis].

PMID- 15427962
TI  - [Effect of oxygen-poor air mixtures on the circulation in normal and cardiac
      states].

PMID- 15427963
TI  - [Infarct of the myocardium].

PMID- 15427964
TI  - [Thorn's test in present practice].

PMID- 15427965
TI  - [Cyto-diagnosis of cancer].

PMID- 15427966
TI  - [Certain considerations in bronchiectasis syndrome].

PMID- 15427967
TI  - [Cardiovascular complications in digestive infections].

PMID- 15427968
TI  - [Technic of quantitative Wassermann reaction; use of photo-electric colorimeter
      for standardization of reagents and in reading the test].

PMID- 15427969
TI  - [Diverticula of the first portion of the duodenum].

PMID- 15427970
TI  - [Congenital dextrocardia; report of 13 cases].

PMID- 15427971
TI  - [Hypertrophic stenosis of the pylorus].

PMID- 15427972
TI  - [Chronaxia, curare and prostigmine in man].

PMID- 15427973
TI  - [Endocrine allergy; the problem in its general outline].

PMID- 15427974
TI  - [Peritoneal pseudomyxoma].

PMID- 15427975
TI  - [Preparation of antigens for the diagnosis and therapy of bacterial allergy. IV.
      Antigens of enterobacteria (Escherichia, Aerobacter, Klebsiella, Proteus,
      Salmonella, Shigella)].

PMID- 15427976
TI  - New 87-bed chronic disease hospital in San Francisco.

PMID- 15427977
TI  - What are responsibilities of planners in equipping a hospital?

PMID- 15427978
TI  - GROUP, regional cooperation urged at Catholic hospital convention.

PMID- 15427979
TI  - The president's address.

PMID- 15427980
TI  - Value of graduate administration courses upheld by Catholic convention panel.

PMID- 15427981
TI  - WANT to improve purchasing methods? Hospital executives offer suggestions.

PMID- 15427982
TI  - HOSPITAL gives home care.

PMID- 15427983
TI  - A symposium on the administrative residency.

PMID- 15427984
TI  - Are you making plans to care for patients with psychiatric disorders?

PMID- 15427985
TI  - Safety measures in oxygen therapy.

PMID- 15427986
TI  - If Blue Cross is to survive here is what must be done.

PMID- 15427987
TI  - Establishing administrative standards for the hospital nursing service.

PMID- 15427988
TI  - NURSING education and college levels.

PMID- 15427989
TI  - A flexible state program for nursing education.

PMID- 15427990
TI  - NURSE recruitment ad campaign for 50,000 students under way.

PMID- 15427991
TI  - Streptomycin, white hope in modern TB therapy.

PMID- 15427992
TI  - Planning, equipping and appraising hospital dietary facilities.

PMID- 15427993
TI  - GENERAL menus for August, suitable for staff, personnel and patients not
      requiring special diets.

PMID- 15427994
TI  - A report on the How's Business Questionnaire.

PMID- 15427995
TI  - Ninety-eight beds and a board.

PMID- 15427997
TI  - HOW are you going to remove those stains? Here are expert answers.

PMID- 15427996
TI  - Some medical-legal problems and suggestions for their solution.

PMID- 15427998
TI  - Technical aspects of laundry which administrator should know.

PMID- 15427999
TI  - What hospitals can do when the A-bomb falls.

PMID- 15428000
TI  - Caring for the mentally ill.

PMID- 15428001
TI  - Safety measures in oxygen therapy.

PMID- 15428002
TI  - Legal liability, the hospital and the medical record.

PMID- 15428003
TI  - Nursing in the acute stage of poliomyelitis.

PMID- 15428004
TI  - Establishing a hospital formulary in the hospital pharmacy.

PMID- 15428005
TI  - Streptomycin--white hope in modern TB therapy.

PMID- 15428007
TI  - Credits and collections.

PMID- 15428006
TI  - Planning, equipping and appraising hospital dietary facilities.

PMID- 15428008
TI  - Some medical-legal problems and suggestions for their solution.

PMID- 15428009
TI  - THIRTY-FIFTH annual convention of the Catholic Hospital Association.

PMID- 15428010
TI  - Report on third annual meeting of the Conference of Catholic Schools of Nursing.

PMID- 15428011
TI  - Old age and survivors insurance.

PMID- 15428012
TI  - When laymen pitch in--the hospital gains.

PMID- 15428014
TI  - The lowly dietitian.

PMID- 15428013
TI  - The faculty of a Catholic nursing school.

PMID- 15428015
TI  - Lifting an unwanted curtain of mystery.

PMID- 15428016
TI  - SPEECH without a larynx.

PMID- 15428017
TI  - All profit from sisters' staff meeting.

PMID- 15428018
TI  - Catholic hospitals help Blue Cross enrollment in S. Dakota.

PMID- 15428019
TI  - Catholic hospitals help Blue Cross enrollment in Maine.

PMID- 15428020
TI  - GREATER fire safety for older buildings.

PMID- 15428021
TI  - RECRUITMENT troubles? An Ohio solution.

PMID- 15428022
TI  - Delivery of hydrocephalic infant.

PMID- 15428023
TI  - A practical religion course.

PMID- 15428024
TI  - Aid to medical schools.

PMID- 15428025
TI  - Treatment of peripheral vascular disorders.

PMID- 15428027
TI  - Chemotherapy of cancer.

PMID- 15428026
TI  - Observations on the use of aureomycin in the treatment of acute anterior
      poliomyelitis.

PMID- 15428028
TI  - Cavernous hemangioma of the liver.

PMID- 15428029
TI  - Dermatitis medicamentosa caused by mesantoin.

PMID- 15428030
TI  - Transurethral resection of the prostate gland.

PMID- 15428031
TI  - Local antihistaminic agents in ophthalmology.

PMID- 15428032
TI  - Management of abortions.

PMID- 15428033
TI  - Recent developments in endocrinology.

PMID- 15428034
TI  - Physical medicine and rehabilitation in the Veterans Administration.

PMID- 15428035
TI  - Case of chest trauma.

PMID- 15428036
TI  - Cardiac aneurysm demonstrated by angiocardiography.

PMID- 15428037
TI  - [Lead poisoning in industry].

PMID- 15428038
TI  - [Nervous trophism in the theory and practice of medicine].

PMID- 15428039
TI  - [Treatment of anxiety states and pain].

PMID- 15428040
TI  - [Final commentary on the study of the nervous system].

PMID- 15428041
TI  - [Educational factor in the success of industrial hygiene standards].

PMID- 15428043
TI  - [The so-called juvenile delinquency].

PMID- 15428042
TI  - [Problem of re-education of abnormal children].

PMID- 15428044
TI  - [Anatomical treatise on the movements of the heart and the blood in animals].

PMID- 15428045
TI  - [William Harvey: his anatomical treatise on the movements of the heart and blood
      in animals].

PMID- 15428046
TI  - Streptomycin in tick-borne relapsing fever of Kashmir.

PMID- 15428047
TI  - Echinococcal cyst of broad ligament.

PMID- 15428048
TI  - Pneumoperitoneum in the study of hepatic abscess.

PMID- 15428049
TI  - Generalized cysticercosis cellulosae.

PMID- 15428050
TI  - Some constituents in normal blood in central India; serum proteins, serum
      albumin, serum globulin and serum non-protein nitrogen.

PMID- 15428051
TI  - Creeping myiasis in man; an unusual case.

PMID- 15428053
TI  - Typhus in Mylliem State area, Shillong.

PMID- 15428052
TI  - Epidemic dropsy complicating pregnancy.

PMID- 15428054
TI  - A case of xerodermia pigmentosa in a Singhalese.

PMID- 15428055
TI  - Effect of fibrolysin and antithyroidin on Raynaud's disease (after
      sympathectomy).

PMID- 15428056
TI  - Brief notes on two cases of scrub typhus fever with unusual neurological signs.

PMID- 15428057
TI  - Dehydration and its treatment.

PMID- 15428058
TI  - PARA-AMINOSALICYLIC acid: PAS.

PMID- 15428059
TI  - Stethoscope and the heart.

PMID- 15428060
TI  - Hypertrophy of the prostate.

PMID- 15428062
TI  - SHOCK therapy in mental diseases.

PMID- 15428061
TI  - On the administration of Pure Food Act in India.

PMID- 15428063
TI  - INDIAN Research Fund Association.

PMID- 15428064
TI  - Central Research Institute, Kasauli (Simla Hills).

PMID- 15428065
TI  - Nutrition Research Laboratories.

PMID- 15428066
TI  - All-India Institute of Hygiene and Public Health, Calcutta.

PMID- 15428067
TI  - The Malaria Institute of India.

PMID- 15428068
TI  - Indian Institute for Medical Research.

PMID- 15428069
TI  - School of Tropical Medicine.

PMID- 15428070
TI  - The King Institute of Preventive Medicine, Madras.

PMID- 15428071
TI  - Note on the contribution of the Indian Medical Service to medical research in
      India.

PMID- 15428072
TI  - Bengal Immunity Research Institute, Calcutta.

PMID- 15428073
TI  - Tata Memorial Hospital, Bombay.

PMID- 15428074
TI  - MEDICAL Research Council, London.

PMID- 15428075
TI  - IMPERIAL Cancer Research Fund, London.

PMID- 15428076
TI  - The Lister Institute of Preventive Medicine.

PMID- 15428077
TI  - Connaught Medical Laboratories, University of Toronto, Canada.

PMID- 15428078
TI  - The Wellcome Research Institution, London.

PMID- 15428079
TI  - CIBA foundation for the Promotion of International Cooperation in Medical and
      Chemical Research.

PMID- 15428081
TI  - Medical research organization in Soviet Russia.

PMID- 15428080
TI  - Inaugural address.

PMID- 15428082
TI  - Medical research in Australia.

PMID- 15428083
TI  - NUFFIELD Foundation, London.

PMID- 15428084
TI  - Evolution of small plant health service as a private practice.

PMID- 15428085
TI  - Solving the solvent problem.

PMID- 15428086
TI  - Cyclohexylamine, p-chlornitrobenzene, 2-aminopyridine: toxic effects in
      industrial use.

PMID- 15428087
TI  - The toxicologist and industrial toxicology.

PMID- 15428088
TI  - Medicolegal and social problems of non-occupational temporary disability
      benefits.

PMID- 15428089
TI  - The Detroit plan for first aid and emergency medical services in small plants.

PMID- 15428090
TI  - WHO'S who in industrial medicine: Loyal A. Shoudy; M. D.

PMID- 15428091
TI  - The sugar industry.

PMID- 15428092
TI  - Plantation medicine past, present, and future.

PMID- 15428093
TI  - Plantation medical plan.

PMID- 15428094
TI  - Recent trends in established and accepted fracture treatment methods.

PMID- 15428095
TI  - A case report on rheumatoid arthritis.

PMID- 15428096
TI  - Annual report of the Medical Adviser, Hawaiian Sugar Planters' Association,
      October 1948 to October 1949.

PMID- 15428097
TI  - Pineapple plantations' prudential plan.

PMID- 15428098
TI  - A plantation manager talks to the doctors.

PMID- 15428099
TI  - Industrial application of preventive medicine.

PMID- 15428100
TI  - The industrial patient.

PMID- 15428101
TI  - PANEL: Heart disease in relation to employment.

PMID- 15428102
TI  - When a plantation hospital is discontinued.

PMID- 15428103
TI  - Treatment of eye injuries on a plantation.

PMID- 15428104
TI  - Industrial eye programs in Hawaii.

PMID- 15428105
TI  - Head injuries.

PMID- 15428106
TI  - Treatment of chest injuries.

PMID- 15428107
TI  - Essentials of superficial roentgen therapy; an outline for the general
      practitioner.

PMID- 15428108
TI  - Influences of the unusual on plant medical activities.

PMID- 15428109
TI  - Occupational disease manifestations in dental impairments.

PMID- 15428110
TI  - [Odontoplastic impressions; crown-inlays].

PMID- 15428111
TI  - [Classical bi-maxillary endognathy].

PMID- 15428112
TI  - [Dental accident due to decompression].

PMID- 15428113
TI  - [Always on the subject of "depulpation"].

PMID- 15428114
TI  - [Treatment of stomatitis by combination of sulfamide and tyrothricin].

PMID- 15428115
TI  - [Use of orthodontic apparatus at an early age].

PMID- 15428116
TI  - [Radiologic aspects of the teeth in general diseases].

PMID- 15428117
TI  - [Consequences of malformation of the maxilla due to mesio-position of the sixth
      year molar].

PMID- 15428118
TI  - [Replacement of facings in a bridge in the mouth].

PMID- 15428119
TI  - [Sjogren's syndrome].

PMID- 15428120
TI  - [Lysis of a root provoked by an impacted tooth].

PMID- 15428121
TI  - [Concerning depulpation].

PMID- 15428123
TI  - [The evolution of odonto-stomatology].

PMID- 15428122
TI  - [Dental caries, a solved biochemical problem].

PMID- 15428124
TI  - [Odontoplastic castings; pivot crowns].

PMID- 15428125
TI  - [Leukoplakia of the mouth].

PMID- 15428126
TI  - [The dialogues of Pelican and Hummingbird].

PMID- 15428127
TI  - [The misadventures of the dental surgeon of his most serene the Abbey of Saint
      Germain-des-Pres].

PMID- 15428128
TI  - [Determination of occlusion with an instantaneous automatic intra-buccal
      occlusor].

PMID- 15428129
TI  - [Therapy of desensitization and reactivation of the periodontium by mineral
      water].

PMID- 15428130
TI  - [Combination of sulfamide and tyrothricin].

PMID- 15428131
TI  - [A new process for invisible fixation of fixed prostheses].

PMID- 15428132
TI  - [Depulpation].

PMID- 15428133
TI  - [Naphthalene in the treatment of alveoloradicular inflammation].

PMID- 15428134
TI  - The autonomic nervous system in relation to etiology and management of allergic
      disease.

PMID- 15428135
TI  - The role of emotions in allergic diseases.

PMID- 15428136
TI  - Asthma in children as a psychosomatic disease.

PMID- 15428137
TI  - The possible influence of psychological factors in brucella allergy.

PMID- 15428138
TI  - A new approach to the problem of dust allergy.

PMID- 15428139
TI  - Patterns in contact dermatitis.

PMID- 15428140
TI  - Allergic eczema.

PMID- 15428141
TI  - Hypersensitivity to fluorescein; a case of anaphylactic reaction to the injection
      of fluorescein sodium.

PMID- 15428142
TI  - [Occupational dermatitis caused by sunflower seeds and linseeds].

PMID- 15428143
TI  - [Michurin and present times].

PMID- 15428144
TI  - [History of struggle for materialistic biology in Russia].

PMID- 15428145
TI  - [Process of fertilization of angiospermatic plants].

PMID- 15428146
TI  - [Dynamics of hydrocarbons, nitrogen substances and ferment activity in relation
      to nutritional conditions of the plant in crop rotation of beets].

PMID- 15428147
TI  - [Effect of overgrowing of the tea plant on the content of tannic substances in
      the green leaves].

PMID- 15428148
TI  - [New law of conformity in the content of nutritional elements in plants in
      estimation of nitrogen ash].

PMID- 15428149
TI  - [Ontogenesis and phylogenesis of secondary sex characters in fowl species].

PMID- 15428150
TI  - [Restoration of organic functions following partial transverse resection of the
      spinal cord at the upper levels].

PMID- 15428151
TI  - [Multiple activity of single nervous fibers].

PMID- 15428152
TI  - [Functional state of salivary distribution center in dogs following
      decerebration].

PMID- 15428153
TI  - [Feto-infantile mortality].

PMID- 15428154
TI  - [Mission of aeronautical medicine].

PMID- 15428155
TI  - [New prospectives in vaccination against tuberculosis by B.C.G..].

PMID- 15428156
TI  - [Arterial hypertension and the nervous system].

PMID- 15428157
TI  - [Clinico-psychological analysis of stammering in a child].

PMID- 15428158
TI  - [Unusual point of entrance in a case of rickettsiasis conori].

PMID- 15428159
TI  - [Medicine advances constantly invading the field of surgery].

PMID- 15428160
TI  - [Arterial hypertension and the nervous system].

PMID- 15428161
TI  - [Prevention of eye accidents in industry].

PMID- 15428162
TI  - Some personality and social factors related to changes in children's attitudes
      toward Negroes.

PMID- 15428163
TI  - Attitude and structure as factors in the distortion of reasoning.

PMID- 15428164
TI  - Perceptual selectivity in Rorschach determinants as a function of depressive
      tendencies.

PMID- 15428165
TI  - Changes in performance in relation to influences upon self-conceptualization.

PMID- 15428166
TI  - Some data bearing on the Oedipus hypothesis.

PMID- 15428167
TI  - An inquiry concerning the characteristics of man.

PMID- 15428168
TI  - The reliability and validity of the Horowitz Faces Test.

PMID- 15428169
TI  - A method of validation by successive clinical predictions.

PMID- 15428170
TI  - The comparative effect of frustration and success on goal-directed behavior in
      the classroom.

PMID- 15428171
TI  - The phenomenological approach in personality theory: some critical remarks.

PMID- 15428172
TI  - The phenomenological approach and the problem of "unconscious" behavior: a reply
      to Dr. Smith.

PMID- 15428173
TI  - Psychoanalysis, deductive method, and the Blacky Test.

PMID- 15428174
TI  - A reply to Seward's "Psychoanalysis, deductive method, and the Blacky Test.".

PMID- 15428175
TI  - Notes on the conception of the self among the Wintu Indians.

PMID- 15428176
TI  - The intelligence of American children of Mexican parentage.

PMID- 15428177
TI  - The spatial factor in face to face discussion groups.

PMID- 15428178
TI  - The perception of persons: forecasting another person's responses on three
      personality scales.

PMID- 15428179
TI  - Role of the adrenal cortex in immunity.

PMID- 15428180
TI  - The effect of cortisone of bronchial asthma and hay fever occurring in subjects
      sensitive to ragweed pollen.

PMID- 15428181
TI  - The effect of cortisone on bronchial asthma.

PMID- 15428182
TI  - The effect of adrenocorticotrophic hormone (ASTH) on patients with allergic
      diseases--facts and speculations.

PMID- 15428183
TI  - The effect of pituitary adrenocorticotrophic hormone (ACTH) on histamine
      intoxication and anaphylaxis in the guinea pig.

PMID- 15428184
TI  - The effect of cortisone upon the release of histamine during in vitro hemolytic
      reactions in rabbit blood.

PMID- 15428185
TI  - The effect of tripelennamine hydrochloride (pyribenzamine) on the release of
      histamine during in vitro hemolytic reaction in rabbit blood.

PMID- 15428186
TI  - In vitro release of histamine by hypersensitive (allergic) serum in contrast to
      immune (treated) allergic serum in antigen and normal rabbit blood mixtures.

PMID- 15428187
TI  - Pollen tolerance nasal tests in hay fever experimental and clinical observations.

PMID- 15428188
TI  - The incidence of abnormal electroencephalographic patterns in allergic children.

PMID- 15428189
TI  - Bronchiectasis in asthma.

PMID- 15428190
TI  - Failure to prevent experimental eczematous sensitization: observations on the
      "spontaneous" flare-up phenomenon.

PMID- 15428191
TI  - Cardiorespiratory function in relation to asthma and emphysema; viewpoint of the
      allergist.

PMID- 15428192
TI  - Newer antihistaminics: III. Some pharmacologic and therapeutic effects of beta-(p
      mehtylbenzhydryloxy)-ethyldimethylamine hydrochloride, derivative of
      diphenhydramine hydrochloride.

PMID- 15428193
TI  - The effect of radioactive phosphorus upon the development of the teeth and
      mandibular joint of the mouse.

PMID- 15428194
TI  - Dental roentgenography; the voltage factor (kv.p.).

PMID- 15428195
TI  - Distortion of wax patterns as influenced by storage time, storage temperature,
      and temperature of wax manipulation.

PMID- 15428196
TI  - Excessive citrus juice consumption. Clinical observations of its effect on
      superficial and deep tissues of the oral cavity.

PMID- 15428197
TI  - Age determination on teeth.

PMID- 15428198
TI  - Bacteremia following tooth extraction: prevention with penicillin and N U 445.

PMID- 15428199
TI  - The effects of a penicillin dentifrice on oral lactobacilli.

PMID- 15428200
TI  - Full denture construction from the obtaining of the centric maxillomandibular
      record to completion of the dentures.

PMID- 15428201
TI  - Submaxillary phlegmon of dental origin treated with aureomycin.

PMID- 15428202
TI  - Prosthetic restoration of soft palate lost as a result of diphtheria: report of a
      case.

PMID- 15428203
TI  - A case report of a paradental cyst.

PMID- 15428204
TI  - Benefits from prophylactic use of penicillin before dental extractions.

PMID- 15428205
TI  - Rapid diffuse penetration of intact enamel and dentin by carbon 14-labeled urea.

PMID- 15428206
TI  - Control of dental caries by the addition of fluorides to public water supplies.

PMID- 15428207
TI  - Dentistry for the cerebral palsied.

PMID- 15428208
TI  - The use of the toothbrush in the treatment of periodontitis.

PMID- 15428209
TI  - The application of biochemical methods to dental research.

PMID- 15428210
TI  - The role of the precision attachment in partial denture prosthesis.

PMID- 15428211
TI  - Root canal therapy for the developing and adult dentition; its importance in
      complete mouth rehabilitation.

PMID- 15428212
TI  - Naturally occurring stains on the teeth of children.

PMID- 15428213
TI  - The detection of carious lesions on the proximal surfaces of teeth.

PMID- 15428214
TI  - A physical lock of the temporomandibular joint.

PMID- 15428215
TI  - Temporomandibular arthrogryposis with gingival involvement.

PMID- 15428217
TI  - STUDY of terms: the concept "bifurcation".

PMID- 15428216
TI  - Observations on methylmethacrylate filling material.

PMID- 15428218
TI  - NINETEEN fifty survey of the dental profession.

PMID- 15428219
TI  - APPROVED hospital dental departments.

PMID- 15428220
TI  - COUNCIL announces classification of additional products.

PMID- 15428221
TI  - Utilization of carotene and vitamin A by hyperthyroid and pregnant rats.

PMID- 15428222
TI  - Calculation of diabetic diets.

PMID- 15428223
TI  - Effect of adding soy flour upon the protein value of baked products.

PMID- 15428224
TI  - Effect of cocoa on protein utilization.

PMID- 15428225
TI  - Observations on protein improvements of low-extraction wheat flour;
      supplementation with soya or cereal germ in an Italian nutrition program.

PMID- 15428226
TI  - Trends in family food consumption.

PMID- 15428227
TI  - Treatment of thyrotoxicosis with radioactive iodine.

PMID- 15428228
TI  - Training and career management in the Medical Corps.

PMID- 15428229
TI  - Inapparent Salmonella infections in hospitals.

PMID- 15428230
TI  - Surgical treatment of gastrojejunal ulcer.

PMID- 15428231
TI  - Diagnosis of pheochromocytoma by the adrenergic blocking action of benzodioxan.

PMID- 15428232
TI  - The burn problem in atomic warfare.

PMID- 15428233
TI  - Multiple sclerosis.

PMID- 15428234
TI  - Peripheral facial palsy; multiple attacks in three brothers.

PMID- 15428235
TI  - NEW and nonofficial remedies: p-nitrosulfathiazole; nisulfazole.

PMID- 15428236
TI  - NEW and nonofficial remedies: methylhexamine; forthane.

PMID- 15428237
TI  - NEW and nonofficial remedies: pyranisamine maleate; neo-antergan maleate.

PMID- 15428238
TI  - NEW and nonofficial remedies: plasma hydrolysates; travamin.

PMID- 15428239
TI  - NEW and nonofficial remedies: zincundesal; salundek.

PMID- 15428240
TI  - FAIRCHILD-Huxley chest respirator accepted.

PMID- 15428241
TI  - MINUTES of the annual session of the House of Delegates of the American Medical
      Association, held in San Francisco, June 26-30, 1950.

PMID- 15428242
TI  - Medical care prices vs. cost of living.

PMID- 15428243
TI  - MALPRACTICE; fraudulent concealment of failure to remove gallbladder.

PMID- 15428244
TI  - Neurotoxic reactions to dihydrostreptomycin.

PMID- 15428245
TI  - Subclinical carcinoma of cervix uteri; evaluation of endocervical curettage in
      detection and differential diagnosis of preinvasive and covert invasive
      carcinoma.

PMID- 15428246
TI  - Factors responsible for laryngeal obstruction in infants.

PMID- 15428247
TI  - Pediatric care under the North Carolina plan.

PMID- 15428248
TI  - Preovulatory administration of methyltestosterone in refractory functional
      dysmenorrhea.

PMID- 15428250
TI  - Treatment of multiple sclerosis; a review of drug therapy.

PMID- 15428251
TI  - Aspiration of the heart in air embolism.

PMID- 15428252
TI  - Mineral deficiencies.

PMID- 15428253
TI  - NEW and nonofficial remedies: sulfoxone sodium; diasone sodium.

PMID- 15428254
TI  - NEW and nonofficial remedies: testosterone propionate.

PMID- 15428255
TI  - Analysis of a statement on medical care.

PMID- 15428256
TI  - PRIVILEGED communications cannot be claimed by defendant in criminal prosecution.

PMID- 15428257
TI  - Congenital dislocation of the hip in the newborn and in early postnatal life.

PMID- 15428258
TI  - Terramycin in the treatment of pneumococcic and primary atypical pneumonia.

PMID- 15428259
TI  - Abrasive balloon for exfoliation of gastric cancer cells.

PMID- 15428260
TI  - Follow-up study of one hundred private hypertensive patients with cardiovascular
      complications.

PMID- 15428261
TI  - Endocrine control of prostatic carcinoma; clinical and statistical survey of
      1,818 cases.

PMID- 15428262
TI  - The medical care of the veteran.

PMID- 15428264
TI  - Diabetes mellitus in association with myasthenia gravis.

PMID- 15428263
TI  - Successful treatment of hyperhidrosis using banthine.

PMID- 15428265
TI  - Aureomycin in epidemic parotitis.

PMID- 15428266
TI  - Toxic psychosis due to overdosage with prophenpyridamine (trimeton); report of
      two cases with recovery.

PMID- 15428267
TI  - Femoral hernia; report of two unusual cases.

PMID- 15428268
TI  - Meningitis during gold therapy.

PMID- 15428269
TI  - Foods of animal origin.

PMID- 15428270
TI  - NEW and nonofficial remedies: vitamin B12-U.S.P.; cobione.

PMID- 15428271
TI  - NEW and nonofficial remedies: pentobarbital; nembutal.

PMID- 15428272
TI  - NEW and nonofficial remedies: pentobarbital calcium; nembutal calcium.

PMID- 15428273
TI  - NEW and nonofficial remedies: thiamine hydrochloride.

PMID- 15428274
TI  - NEW and nonofficial remedies: tyrothricin.

PMID- 15428275
TI  - NEW and nonofficial remedies: sulfamerazine.

PMID- 15428276
TI  - CHIROPRACTIC practice acts: requirements for reciprocity certificate (South
      Carolina).

PMID- 15428278
TI  - ADMISSIBILITY in evidence of medical books or treatises.

PMID- 15428277
TI  - MALPRACTICE: failure of osteopath to ligate ruptured cervical artery following
      childbirth.

PMID- 15428279
TI  - MEDICAL practice acts: use of injunction to restrain unlawful practice of
      medicine by chiropractor.

PMID- 15428280
TI  - Electrophrenic respiration in acute bulbar poliomyelitis; its use in management
      of respiratory irregularities.

PMID- 15428281
TI  - Myeloid metaplasia.

PMID- 15428282
TI  - Pathogenesis of urticaria; experimental study of life situations, emotions and
      cutaneous vascular reaction.

PMID- 15428283
TI  - Meningitis due to simultaneous double infections in children.

PMID- 15428284
TI  - Chloramphenicol in the treatment of hemophilus influenzae meningitis.

PMID- 15428285
TI  - Treatment of hyperthyroidism with 1-methyl-2-mercaptoimidazole.

PMID- 15428286
TI  - Mesenteric vascular occlusion; extensive resection of the small intestine with
      survival.

PMID- 15428287
TI  - Pedunculated ball thrombus in a hypertensive heart.

PMID- 15428288
TI  - BURDICK electrocardiograph, model EK-1, accepted.

PMID- 15428289
TI  - The absorption and excretion of rutin and related flavonoid substances.

PMID- 15428290
TI  - ACCEPTED foods.

PMID- 15428291
TI  - Medical care in England under the National Health Service; report to the Board of
      Trustees of the American Medical Association.

PMID- 15428292
TI  - Chloramphenicol (chloromycetin) therapy in Shigella enteritis.

PMID- 15428293
TI  - Mesantoin in epilepsy; report of 80 cases.

PMID- 15428294
TI  - Use of ergot preparations in migraine.

PMID- 15428295
TI  - The normal blood pressure range and its clinical implications.

PMID- 15428296
TI  - Relation of brucellosis and multiple sclerosis.

PMID- 15428297
TI  - Brucellosis and multiple sclerosis.

PMID- 15428299
TI  - Hairy tongue.

PMID- 15428298
TI  - Rheumatoid arthritis; effects of certain steroids other than cortisone and of
      some adrenal cortex extracts.

PMID- 15428300
TI  - Air embolism in blood donors.

PMID- 15428301
TI  - NEW and nonofficial remedies: anti-Hemophilus influenzae type B serum (rabbit).

PMID- 15428302
TI  - NEW and nonofficial remedies: salicylanilide-N.F.; ansadol.

PMID- 15428303
TI  - NEW and nonofficial remedies: estrogenic substances (water soluble); ethinyl
      estradiol.

PMID- 15428304
TI  - NEW and nonofficial remedies: heparin sodium.

PMID- 15428305
TI  - NEW and nonofficial remedies: influenza virus vaccine, types A and B.

PMID- 15428306
TI  - NEW and nonofficial remedies: mannitol hexanitrate.

PMID- 15428308
TI  - NEW and nonofficial remedies: methyltestosterone.

PMID- 15428307
TI  - NEW and nonofficial remedies: mersalyl and theophylline.

PMID- 15428309
TI  - NEW and nonofficial remedies: nitrofurazone.

PMID- 15428310
TI  - NEW and nonofficial remedies: typhoid vaccine.

PMID- 15428311
TI  - NEW and nonofficial remedies: vitamin B12 U.S.P.

PMID- 15428313
TI  - SANBORN viso-cardiette, model 51, accepted.

PMID- 15428312
TI  - ACCEPTED food.

PMID- 15428314
TI  - DeVILBISS steam vaporizer, No. 149, accepted.

PMID- 15428315
TI  - AEROHALOR (powder inhaler) accepted.

PMID- 15428316
TI  - GRASS electroencephalograph, model III-C, accepted.

PMID- 15428317
TI  - British medical education and the National Health Service; a report to the
      trustees of the American Medical Association.

PMID- 15428318
TI  - CHARITABLE hospitals; immunity of trust funds from judgment for damages due to
      negligence.

PMID- 15428319
TI  - Agglutination with sensitized sheep cells in rheumatoid arthritis.

PMID- 15428320
TI  - Female infertility and sterility, endocrine factors.

PMID- 15428321
TI  - Progress in psychiatry.

PMID- 15428322
TI  - TREATMENT of peptic ulcer.

PMID- 15428323
TI  - The international tuberculosis campaign.

PMID- 15428324
TI  - International cancer meetings.

PMID- 15428325
TI  - Medical women and group practice as seen by a Canadian.

PMID- 15428326
TI  - Medical women in Finland.

PMID- 15428327
TI  - Rachel Forster Hospital for Women and Children, Sydney, Australia.

PMID- 15428328
TI  - Detection of cancer of the uterus; report on 4,500 routine cervical smears.

PMID- 15428329
TI  - TREATMENT of peptic ulcer.

PMID- 15428330
TI  - Handwriting as a diagnostic aid.

PMID- 15428331
TI  - The Olcott Memorial Hospital in Kuwait, Arabia.

PMID- 15428333
TI  - Basic principles of osteopathy.

PMID- 15428332
TI  - Dedications in books by medical women.

PMID- 15428334
TI  - Hyperproteinization; use in rheumatic fever.

PMID- 15428335
TI  - Anomalous auriculoventricular excitation; the Wolff-Parkinson-White syndrome.

PMID- 15428336
TI  - The early diagnosis of cancer.

PMID- 15428337
TI  - Surgical principles.

PMID- 15428338
TI  - Pitfalls and errors in roentgen gastrointestinal examination.

PMID- 15428339
TI  - The use of posterior pituitary extract in the first stage of labor.

PMID- 15428340
TI  - Phlebothrombosis and thrombophlebitis in obstetrics and gynecology.

PMID- 15428341
TI  - Obstetrical considerations of human trophoblast.

PMID- 15428342
TI  - Episiotomy and repair.

PMID- 15428344
TI  - Diabetes mellitus complicating pregnancy.

PMID- 15428343
TI  - Uterine inversion following childbirth with case history of spontaneous
      reinversion.

PMID- 15428345
TI  - Endometriosis.

PMID- 15428346
TI  - An evaluation of osteopathic education; a tribute to Dr. Andrew Taylor Still.

PMID- 15428347
TI  - Primary bronchogenic carcinoma.

PMID- 15428348
TI  - Hemorrhage of the nose; practical anatomical considerations and treatment.

PMID- 15428349
TI  - Report on 636 resections of the proximal phalanges of the foot.

PMID- 15428351
TI  - Superficial corneal trauma; an analysis of 117 consecutive cases.

PMID- 15428350
TI  - Fundamentals of x-ray technic.

PMID- 15428352
TI  - Osptopathic students' plans for the future.

PMID- 15428353
TI  - Pharmacological studies on the antispasmodic, beta-diethylaminoethyl 1
      cyclohexylcyclo-hexanecarboxylate hydrochloride.

PMID- 15428354
TI  - A further study of the reaction of theophylline with barbiturates.

PMID- 15428355
TI  - The relationship of structure and antibacterial activity in the nitrofurans.

PMID- 15428356
TI  - Digitalis. IX. A spectroscopic study of the Baljet reaction for digitoxin and
      digitoxigenin.

PMID- 15428357
TI  - An investigation of high-vacuum freeze drying as a means of drug preservation. I.

PMID- 15428358
TI  - Some new procedures and instruments useful for microbiological antibiotic testing
      by diffusion methods. IV. Apparatus for a new method employing linear diffusion
      into inoculated agar-filled glass capillaries.

PMID- 15428359
TI  - Some new procedures and instruments useful for microbiological antibiotic testing
      by diffusion methods; V. A test procedure employing linear diffusion into
      inoculated agar-filled glass capillaries.

PMID- 15428360
TI  - The effect of radical substitution on the optical properties of some
      antihistaminics.

PMID- 15428361
TI  - A chemical assay for salts of dihydrostreptomycin.

PMID- 15428362
TI  - Effect of pantothenic acid antagonists on the action of choline acetylase.

PMID- 15428363
TI  - The absorption and excretion of a liquid polyethylene glycol.

PMID- 15428364
TI  - Chemical and physical examination of some polyethylene glycols.

PMID- 15428365
TI  - The toxicology of the polyethylene glycols.

PMID- 15428366
TI  - Comparison of analgetic activity of 67 arylalkamines with that of morphine and
      meperidine by the mouse hot plate method.

PMID- 15428367
TI  - A note on the diet and care of cats in the laboratory.

PMID- 15428368
TI  - Absence of toxic effects from single injections of crystalline vitamin B12.

PMID- 15428369
TI  - A note concerning the incompatibility of vitamin B12 and ascorbic acid.

PMID- 15428370
TI  - An ink writer for recording blood pressure, respiration, and other responses in
      small animals.

PMID- 15428371
TI  - Pharmaceutical studies with thiamine mononitrate.

PMID- 15428373
TI  - The fallacy of the square root sampling rule.

PMID- 15428372
TI  - The action of various drugs on the arterial blood flow of the pregnant, canine
      uterus.

PMID- 15428374
TI  - Substituted ammonium saccharins for nasal medication.

PMID- 15428375
TI  - The sympathomimetic depressor agents: a review.

PMID- 15428376
TI  - The application of a 2-phase system to the volumetric determination of certain
      medicinal organic compounds.

PMID- 15428377
TI  - The spectrophotometric determination of methapyrilene hydrochloride and related
      antihistaminic derivatives of N-(2-pyridyl)-ethylenediamine.

PMID- 15428378
TI  - Arylaminoheterocyles. V. Ahilino-s-triazines.

PMID- 15428379
TI  - Alpha-chloro-delta-aryloxyvaleric acids.

PMID- 15428380
TI  - The quantitative determination of benzylpenicillin by ultraviolet absorption.

PMID- 15428381
TI  - The preparation and study of some thiazole derivatives of antimony.

PMID- 15428382
TI  - The kinetics of the hydrolysis of procaine.

PMID- 15428383
TI  - Heat sterilization of thermally labile solutions.

PMID- 15428384
TI  - Comparison of the effects of injection of pyrogenic solutions by intravenous and
      intramuscular routes.

PMID- 15428385
TI  - Electrometric titration of volatile oils and volatile oil isolates using lithium
      aluminum hydride.

PMID- 15428386
TI  - Application of lithium aluminum hydride titrimetric method to pharmaceutical
      compounds.

PMID- 15428387
TI  - A note on the preparation of dipicolinic acid.

PMID- 15428388
TI  - A note on the use of pigeons for the assay of digitalis products.

PMID- 15428389
TI  - The veterinarian's responsibility to his community.

PMID- 15428390
TI  - BASKING Ridge small animal hospital.

PMID- 15428391
TI  - The development of an aptitude test for veterinary medicine.

PMID- 15428392
TI  - Diagnosis of liver fluke infection in cattle.

PMID- 15428393
TI  - An approach to the mastitis problem.

PMID- 15428394
TI  - Theileria mutans associated with bovine anaplasmosis in the United States.

PMID- 15428395
TI  - Methods of internal parasite control in sheep and lambs.

PMID- 15428396
TI  - Treatment of infectious sinusitis of turkeys with aureomycin.

PMID- 15428397
TI  - Results of penicillin treatment during an outbreak of erysipelas in turkeys.

PMID- 15428398
TI  - A field test of immunization against Newcastle disease (pneumoencephalitis).

PMID- 15428399
TI  - The practical use of diethylstilbestrol in dairy cattle practice.

PMID- 15428400
TI  - Study of thermocouples as skin thermometers.

PMID- 15428401
TI  - Arterial blood pH and pCO2 changes in response to CO2 inhalation after 24 hours
      of passive hyperventilation.

PMID- 15428402
TI  - Changes in brain pH response to CO2 after prolonged hypoxic hyperventilation.

PMID- 15428403
TI  - Occurrence in normal individuals of diurnal variations in olfactory acuity.

PMID- 15428404
TI  - Mechanical efficiency in cycling of boys seven to fifteen years of age.

PMID- 15428405
TI  - Correlation of acid, pepsin and mucoprotein secretion by human gastric glands.

PMID- 15428406
TI  - Effect of variation in swing radius and arc on incidence of swing sickness.

PMID- 15428407
TI  - The administrative judgment test.

PMID- 15428408
TI  - Menstruation and industrial efficiency; quality and quantity of production.

PMID- 15428409
TI  - Cross-validation of clerical aptitude tests.

PMID- 15428410
TI  - A test battery for actuarial clerks.

PMID- 15428411
TI  - Changes in subjective fatigue and readiness for work during the eight-hour shift.

PMID- 15428412
TI  - Accident proneness of factory departments.

PMID- 15428413
TI  - The rank-comparison rating method.

PMID- 15428414
TI  - Validity of an objectivity key on a short industrial personality questionnaire.

PMID- 15428415
TI  - Getting your message across by plain talk.

PMID- 15428416
TI  - Prediction of academic success in three schools of nursing.

PMID- 15428417
TI  - Critical requirements for dentists.

PMID- 15428418
TI  - The intra-individual relationship between interest and ability.

PMID- 15428419
TI  - A projective test for vocational research and guidance at the college level.

PMID- 15428420
TI  - Preferred rate and extent of the frequency vibrato.

PMID- 15428421
TI  - On the synthesis and some applications of serine-beta-C14.

PMID- 15428422
TI  - Desoxyribose-1-phosphate: I. The phosphorolysis and resynthesis of purine
      desoxyribose nucleoside.

PMID- 15428423
TI  - Desoxyribose-1-phosphate. II. The isolation of crystalline desoxyribose-1
      phosphate.

PMID- 15428424
TI  - Desoxyribose-1-phosphate. III. Comparison of microbiological and
      spectrophotometric estimations of enzymatically produced purine desoxyribose
      nucleoside.

PMID- 15428425
TI  - The role of serine and acetate in uric acid formation.

PMID- 15428426
TI  - The relation of folic acid to the metabolism of serine.

PMID- 15428427
TI  - The nitrogenous metabolism of the earthworm (Lumbricus terrestric). II. Arginase
      and urea synthesis.

PMID- 15428428
TI  - The effectiveness of lactic acid as a hemolytic agent in the determination of
      blood oxygen.

PMID- 15428429
TI  - Metabolism of the thyroid hormone in the rat as shown by physiological doses of
      labeled thyroxine.

PMID- 15428430
TI  - Purification of hyaluronidase.

PMID- 15428431
TI  - Solubility and sedimentation studies on certain pentose nucleic acids.

PMID- 15428432
TI  - A spectrophotometric method for the microdetermination of hexosamines.

PMID- 15428433
TI  - The influence of bile on the alkaline phosphatase activity of intestinal lymph.

PMID- 15428434
TI  - The uptake in vitro of C14-labeled glycine, l-leucine, and l-lysine by different
      components of guinea pig liver homogenate.

PMID- 15428435
TI  - On the mechanism of bacterial fermentation of glucose to lactic acid studied with
      C14-glucose.

PMID- 15428436
TI  - Hyaluronidase inhibitor in blood serum of scorbutic guinea pigs.

PMID- 15428437
TI  - Alpha-Ketoglutaric acid oxidase; an assay procedure.

PMID- 15428438
TI  - The anemis of infection. X. The effect of infection on the absorption and storage
      of iron by the rat.

PMID- 15428439
TI  - The anemia of infection. XI. The effect of turpentine and cobalt on the
      absorption of iron by the rat.

PMID- 15428440
TI  - The anemia of infection. XII. The effect of turpentine and colloidal thorium
      dioxide on the plasma iron and plasma copper of dogs.

PMID- 15428441
TI  - The use of isotopic nitrogen in a study of the conversion of 3-hydroxyanthranilic
      acid to nicotinic acid in Neurospora.

PMID- 15428442
TI  - Isolation of delta 16-androsten-3 (alpha)-oil from the urine of women with
      adrenal cortical tumors.

PMID- 15428443
TI  - The amino acid-sugar reaction.

PMID- 15428444
TI  - Proline and hydroxyproline: purification, reaction with ninhydrin, and some
      properties of their N-nitroso derivatives.

PMID- 15428445
TI  - The effect of insulin and adrenal cortical extract on the hexokinase reaction in
      extracts of muscle from depancreatized cats.

PMID- 15428446
TI  - A micromethod for the determination of xanthine and guanine in urine.

PMID- 15428447
TI  - Preparation and enzymatic hydrolysis of three new homologous dehydropeptides.

PMID- 15428448
TI  - Metabolism of fatty acids in vitro, studied with odd and even members of the
      RC14OOH series.

PMID- 15428449
TI  - Phosphatases of liver. I. Glucose-6-phosphatase.

PMID- 15428450
TI  - Oxidation and transamination of glutamate by typhus rickettsiae.

PMID- 15428451
TI  - The metabolism of 16-ketoestrone and 16-keto-estradiol in man.

PMID- 15428452
TI  - Deuterium studies in normal man. I. The rate of synthesis of serum cholesterol.
      II. Measurement of total body water and water absorption.

PMID- 15428453
TI  - Determinations of ammonia evolved from alpha-amino acids by peri-naphthindan
      2,3,4-trione hydrate and its m-nitro derivative.

PMID- 15428454
TI  - Serum catecholase: properties of the enzyme and nature of an endogenous
      inhibitor.

PMID- 15428455
TI  - Some factors affecting the action of 2,4-dinitrophenol on the oxygen uptake of
      excised rat brain.

PMID- 15428456
TI  - The oxidation of palmitic acid-1-C14 by extrahepatic tissues of the dog.

PMID- 15428457
TI  - Site of formation of plasma phospholipides studied with C14-labeled palmitic
      acid.

PMID- 15428458
TI  - Relative rates of conversion of the various carbon atoms of palmitic acid to
      carbon dioxide by the intact rat.

PMID- 15428459
TI  - The role of glycine in the biosynthesis of heme.

PMID- 15428460
TI  - The role of acetic acid in the biosynthesis of heme.

PMID- 15428461
TI  - Fatty acid synthesis by enzyme preparations of Clostridium kluyveri. VI.
      Reactions of acyl phosphates.

PMID- 15428462
TI  - The relationship of folic acid to formate metabolism in the rat.

PMID- 15428463
TI  - The Biological Photographic Association.

PMID- 15428464
TI  - Homemade camera stand for medical photography.

PMID- 15428465
TI  - Cost finding in medical photography.

PMID- 15428466
TI  - Photomicrography with the concentrated are lamp.

PMID- 15428467
TI  - An improved method of copying in color.

PMID- 15428468
TI  - A small microphone boom and dolly.

PMID- 15428469
TI  - Color temperature: its use in color photography.

PMID- 15428470
TI  - Presidential address.

PMID- 15428471
TI  - Flexor-tendon grafts in the fingers and thumb; an evaluation of end results.

PMID- 15428472
TI  - Congenital metatarsus varus; report of 300 cases.

PMID- 15428473
TI  - Congenital dislocation of the hip; development of the joint after closed
      reduction.

PMID- 15428474
TI  - Congenital dislocation of the hip. Part I. Method of grading results.

PMID- 15428475
TI  - Dual slotted plates in fixation of fractures of the femoral shaft.

PMID- 15428476
TI  - The patella; its importance in derangement of the knee.

PMID- 15428477
TI  - The lumbar neural arch; roentgenographic study of ossification.

PMID- 15428478
TI  - Absorption of protruded disc tissue.

PMID- 15428479
TI  - Partial scapulectomy for snapping of the scapula.

PMID- 15428480
TI  - Study of fracture healing by means of radioactive tracers.

PMID- 15428481
TI  - Unusual fracture-subluxations of the shoulder joint.

PMID- 15428482
TI  - Surgical reconstruction of the paralytic shoulder by multiple muscle
      transplantations.

PMID- 15428483
TI  - Factors determining the deposition and demineralization of bone.

PMID- 15428484
TI  - Clinical manifestations of congenital neurofibromatosis.

PMID- 15428485
TI  - The possible relationship of neurofibromatosis, congenital pseudarthrosis, and
      fibrous dysplasia.

PMID- 15428486
TI  - An analysis of paralytic thumb deformities.

PMID- 15428487
TI  - Some observations on the circulation in foetal and infant spines.

PMID- 15428488
TI  - Observations on discoid menisci.

PMID- 15428489
TI  - Wedge osteotomy for fresh intracapsular fractures of the neck of the femur.

PMID- 15428490
TI  - Legg-Perthes disease; a method of conservative treatment.

PMID- 15428491
TI  - Recession of the gastrocnemius; an operation to relieve spastic contracture of
      the calf muscles.

PMID- 15428492
TI  - Infantile cortical hyperostosis.

PMID- 15428494
TI  - Patella cubiti.

PMID- 15428493
TI  - Anomalies of the carpus; with particular reference to the bipartite scaphoid
      (navicular).

PMID- 15428495
TI  - Ochronosis; a case report.

PMID- 15428496
TI  - Post-traumatic aseptic necrosis of the distal tibial epiphysis; report of a case.

PMID- 15428497
TI  - Bilateral stress fracture of the neck of the femur; report of a case.

PMID- 15428498
TI  - Buttonhook retractor for hand surgery.

PMID- 15428499
TI  - The punching bag in rehabilitation.

PMID- 15428500
TI  - A self-retaining retractor for operations on long bones.

PMID- 15428501
TI  - Universal stapler.

PMID- 15428502
TI  - A table extension to aid in application of shoulder spica.

PMID- 15428503
TI  - Convocation address.

PMID- 15428504
TI  - Full dentures using natural anterior teeth.

PMID- 15428505
TI  - Some psychological implications of dental practice.

PMID- 15428506
TI  - Handsome is as orthodontist does.

PMID- 15428507
TI  - [General anesthesia in dental surgery].

PMID- 15428508
TI  - [New simplified technic for instantaneous clamping and unclamping in jaw
      fractures].

PMID- 15428509
TI  - The disposition of radioactive phosphorus in normal, as compared with
      regenerating and degenerating nervous tissue.

PMID- 15428510
TI  - The effect of anoxia on water exchange and oxygen consumption of onion root
      tissues.

PMID- 15428511
TI  - The ineffectiveness of the connective tissue sheath of nerve as a diffusion
      barrier.

PMID- 15428512
TI  - The uptake of radioactive phosphate by the excised gill of the mussel, Mytilus
      edulis.

PMID- 15428513
TI  - A temperature differentiation of the dual action of amyl carbamate on frog nerve.

PMID- 15428514
TI  - The influence of some sulfhydryl inhibitors and of fluoroacetate on the oxygen
      consumption of some Trypanosomes.

PMID- 15428515
TI  - Alleviation of mitotic poisoning by glucose.

PMID- 15428516
TI  - The respiration of yeast at different concentrations of glucose.

PMID- 15428517
TI  - Prevention of nuclear fusion and mitosis and inhibition of desoxyribonuclease by
      d-usnic acid.

PMID- 15428518
TI  - The potassium permeability of the myelin sheath of a vertebrate nerve.

PMID- 15428519
TI  - The effect of temperature upon the uptake of radioactive phosphate by human
      erythrocytes in vitro.

PMID- 15428520
TI  - Control of phototropic bending of the Avena coleoptile by longitudinally applied
      direct current.

PMID- 15428521
TI  - Some effects of plasma and its fractions on Trypanosoma hippicum.

PMID- 15428522
TI  - The effect of nitrogen mustards on the metabolism of nucleic acids in the
      hematopoietic tissue of the rabbit.

PMID- 15428523
TI  - Ultraviolet light induced delay in cleavage of centrifuged Arbacia eggs.

PMID- 15428524
TI  - The role of adenosine-tri-phosphate in phosphate transfer from yolk to other
      proteins in the developing frog egg. I. General properties of the transfer system
      as a whole.

PMID- 15428525
TI  - The role of adenosine-tri-phosphate in phosphate transfer from yolk to other
      proteins in the developing frog egg. II. Separation of the system into component
      enzymes, phosphate donor and phosphate acceptor.

PMID- 15428527
TI  - SEVENTY-FIFTH anniversary of the Clara Swain Hospital, Bareilly, U.P., October 20
      21, 1949.

PMID- 15428526
TI  - The action of sodium azide upon the oxygen uptake of mitotically active and
      blocked embryos.

PMID- 15428528
TI  - Tuberculosis control in India.

PMID- 15428529
TI  - How slow can the heart rate be; a case study.

PMID- 15428530
TI  - The use of paludrine in malaria prevention.

PMID- 15428531
TI  - The treatment of burns.

PMID- 15428532
TI  - The effect of adrenocorticotropin on the excretion of adrenal metabolites in
      normal human subjects.

PMID- 15428533
TI  - Metabolic studies with adrenocorticotropin in Cushing's syndrome and in virilism.

PMID- 15428534
TI  - Postpartum endometrial hyperplasia in diabetics treated with stilbestrol and
      progesterone.

PMID- 15428535
TI  - A case of ovarian agenesis with normal urinary gonadotropin titer.

PMID- 15428536
TI  - Cyclic changes in the vaginal but not in the uterine mucosa of amenorrheic women,
      induced by a single injection of estrone and progesterone precipitates.

PMID- 15428537
TI  - Neurotoxicity due to thiouracil and thiourea derivatives; a case report.

PMID- 15428538
TI  - Dystrophia myotonica, with special reference to endocrine function (Klinefelter's
      syndrome).

PMID- 15428539
TI  - The level of the circulating eosinophils following trauma.

PMID- 15428540
TI  - The physiologic basis for clinical applications of progesterone.

PMID- 15428541
TI  - The agglutination test in vibrionic abortion of sheep.

PMID- 15428542
TI  - Studies on experimental streptococcal mastitis. I. Inoculation of large numbers
      of Streptococcus agalactiae into the teat canal of goats.

PMID- 15428543
TI  - Studies of experimental streptococcal mastitis. II. Inoculation of varying
      numbers of living Streptococcus agalactiae into the teat canal of goats.

PMID- 15428544
TI  - Studies on experimental streptococcal mastitis. III. Observations on an
      alteration in mouse-lethal power of Streptococcus agalactiae, strain S 13 during
      growth in the udder of goats.

PMID- 15428545
TI  - Some observations on the status of mineral nutrition of nigerian cattle.

PMID- 15428546
TI  - Observations on the value of small daily doses of phenothiazine for the control
      of trichostrongylosis in sheep.

PMID- 15428547
TI  - Lead as a nutritional hazard to farm animals. I. The determination of lead in
      biological material.

PMID- 15428548
TI  - Lead as a nutritional hazard to farm livestock. II. The absorption and excretion
      of lead by sheep and rabbits.

PMID- 15428549
TI  - A methodological study of extinction following aperiodic and continuous
      reinforcement.

PMID- 15428550
TI  - Evidence for continuity in the discrimination of vertical and horizontal
      patterns.

PMID- 15428551
TI  - Hormonal modification of social behavior; the mechanism of estrogen-induced
      dominance in chimpanzees.

PMID- 15428552
TI  - Latent learning under conditions of high motivation.

PMID- 15428553
TI  - Some new experiments on the nature of discrimination learning in the rat.

PMID- 15428554
TI  - Observations on strictly simultaneous conditioned reflexes.

PMID- 15428555
TI  - The hoarding of non-relevant material by the white rat.

PMID- 15428556
TI  - Visual perception and insight in rats.

PMID- 15428557
TI  - The organic elements of the enamel; the gross morphology and the histological
      relationship of the lamellae to the organic framework of the enamel.

PMID- 15428558
TI  - The influence of some surface-active substances on decalcification of the enamel
      surface.

PMID- 15428559
TI  - The weight losses of intact teeth in different buffers at varying pH values.

PMID- 15428560
TI  - Some physical problems involved in the application of solutions to teeth for the
      purpose of reducing dental caries.

PMID- 15428561
TI  - The Evanston Dental Caries Study; the fluorine content of saliva and its
      relationship to (A) oral Lactobacillus counts and (B) the prevalence of dental
      caries.

PMID- 15428562
TI  - Evaluation of the colorimetric (Snyder) test; comparison of positive color
      reactions with the Lactobacillus counts of respective specimens of saliva
      routinely submitted for culture.

PMID- 15428563
TI  - On the occurrence of the lactate fermenting anaerobe, Micrococcus lactilyticus,
      in human saliva.

PMID- 15428564
TI  - The utilization of cereals in various stages of refinement by an oral strain of
      Lactobacillus acidophilus.

PMID- 15428565
TI  - Fluorine, ash, calcium, and phosphorus in human teeth.

PMID- 15428566
TI  - The failure of ammonium ions to inhibit the growth of oral lactobacilli.

PMID- 15428567
TI  - Studies on the incidence and cause of dental defects in children; the deciduous
      molars: fissures and caries.

PMID- 15428568
TI  - Physiological tooth migration and its significance for the development of
      occlusion; the biogenesis of accessional dentition.

PMID- 15428569
TI  - Physiological tooth migration and its significance for the development of
      occlusion; the biogenesis of the successional dentition.

PMID- 15428570
TI  - The effect of pyridoxine deficiency on the jaws of mice; a periodontal
      structures; b. mandibular condyle.

PMID- 15428571
TI  - The effect of x-ray irradiation on the development of the mandibular joint of the
      mouse.

PMID- 15428572
TI  - Salivary ammonia and its correlation to dental calculus; ammonia nitrogen
      development from the supernatant liquid and the residue of centrifuged saliva
      during a 9-day incubation period.

PMID- 15428573
TI  - Salivary ammonia and its correlation to dental calculus; ammonia nitrogen
      development from the washed residue of centrifuged saliva over a 72-hour
      incubation period.

PMID- 15428574
TI  - Salivary ammonia and its correlation to dental calculus; the fate of salivary
      mucin, nonmucin, and ammonia nitrogen over a 72-hour incubation period.

PMID- 15428575
TI  - The effect of propylthiouracil on the periodontium of the hamster.

PMID- 15428576
TI  - Hyaluronidase activity in human saliva.

PMID- 15428577
TI  - Some mechanical characteristics of amalgamators.

PMID- 15428578
TI  - An improved method for the preparation of "serial" sections of undecalcified
      dental tissues.

PMID- 15428579
TI  - The activation effect of calcium on a bactericidal substance for Bacillus
      subtilis in human serum.
AB  - An enhanced bactericidal activity of human serum for B. subtilis develops during
      many different forms of illness, e.g. carcinoma, virus and bacterial infections,
      and during acute coronary occlusion. This increased bactericidal effect cannot be
      related to leucocytosis, fever, serum complement, C-reactive protein, or a
      specific antibody reaction. The serum bactericidal factor becomes inactive in
      decalcified serum, but active again when optimal concentrations of calcium are
      added. Magnesium does not cause reactivation.

PMID- 15428580
TI  - The effect of podophyllotoxin, colchicine, urethane, and nitrogen mustard on the
      respiration of normal and suprarenalectomized rat lymphatic tissue.
AB  - The injection of podophyllotoxin, colchicine, and a nitrogen mustard derivative,
      methyl-bis(beta-chloroethyl)amine, into normal animals causes a reduction of the
      respiration of the lymphatic tissues, spleen, and/or thymus. No effect was
      demonstrable on kidney, a representative tissue of non-lymphatic origin. The
      degree of inhibition was considerably less in suprarenalectomized animals,
      suggesting that the inhibition is mediated by the suprarenal gland.

PMID- 15428581
TI  - The renal mechanism for urate excretion in the Dalmatian coach-hound.
AB  - 1. The renal mechanism for urate excretion in the Dalmatian dog resembles that in
      birds. Urate is cleared at a rate considerably greater than the glomerular
      filtration rate, indicating that its excretion is the result of both glomerular
      filtration and active tubular secretion. The basic physiological mechanisms
      involved in the anomalous purine metabolism of the Dalmatian are indicated and
      their possible biological significance briefly discussed. 2. A new enzymatic
      method for the direct estimation of true urate in biological fluids is described,
      which does not require the estimation of total urate and urate chromogen,
      followed by the calculation of true urate as a difference.

PMID- 15428582
TI  - Stabilization of streptolysin S by potassium ions.
AB  - Potassium ions, and to a less extent, ammonium, magnesium, and barium ions,
      protect streptolysin S against thermal inactivation.

PMID- 15428583
TI  - Acute disseminated encephalomyelitis following immunization with homologous brain
      extracts; studies on the role of a circulating antibody in the production of the
      condition in dogs.
AB  - 1. A severe demyelinating condition characterized by ataxia and paralysis, in
      some instances leading to death, was produced in thirty-five of a total of fifty
      five dogs following immunization with homologous brain tissue combined with
      Freund's adjuvants. In more than 30 per cent of instances paralysis did not occur
      until immunization was continued for 6 or more months. Only eight dogs became
      paralyzed after a single injection of antigen. The condition appeared between 6
      and 15 days after the last injection in all animals, irrespective of the total
      number of injections or the duration of immunization. 2. An antibody which
      reacted in complement fixation tests with aqueous and alcoholic extracts of
      homologous brain tissue was demonstrable in the majority of immunized dogs,
      whether or not the animals became paralyzed. It appeared during or after the 3rd
      week of immunization, and its occurrence or titer could not be correlated with
      the incidence of the encephalomyelitis. In general, there were fewer dogs with
      demonstrable antibody in the paralyzed group than in the non-paralyzed group. 3.
      A flocculation reaction with alcohol extracts of homologous brain was
      demonstrated in the serum of immunized dogs. The antigen and antibody involved
      were apparently identical with those responsible for the complement fixation
      reactions. 4. The brain tissue component which reacted as antigen in the
      complement fixation test was present in adult brain from several mammalian
      species, and peripheral nerve. It was not present in the brain of newborn dogs
      nor in other unrelated organs. It was demonstrable in brain tissue which had been
      allowed to autolyze, or treated with 10 per cent formalin. It was not impaired by
      boiling, or by acid hydrolysis, and was contained in the unsaponifiable fraction
      of brain lipids. It was separable from cholesterol by digitonin precipitation of
      the latter. 5. Immunization of dogs with the unsaponifiable fraction of
      homologous brain, in adjuvants, caused the appearance of antibrain antibody
      similar to that in animals injected with whole brain. Encephalomyelitis was not
      observed during a 2 month period of immunization with this fraction. 6. In guinea
      pigs, an injection of the unsaponifiable fraction of brain, in adjuvants, was
      followed by fatal meningoencephalitis, but the identity of the state with that
      caused by whole brain antigens was not established.

PMID- 15428584
TI  - A viral agent isolated from a case of "non-paralytic poliomyelitis" and
      pathogenic for suckling mice: its possible relation to the coxsackie group of
      viruses.
AB  - 1. A viral agent, Powers, causing myocarditis, adipositis, pancreatitis,
      hepatitis, and encephalomyelitis but not myositis in suckling mice 1 to 2 days
      old has been isolated from the stool of a patient in whom the clinical diagnosis
      was "non-paralytic poliomyelitis." 2. Serological evidence linking the virus to
      the clinical disease observed was clear only in the case of "non-paralytic
      poliomyelitis" from which it was isolated. 3. The possible relation of this agent
      to the Coxsackie group of viruses is discussed. No serological relationship with
      the Connecticut 5, Ohio R, and High Point strains was demonstrated. 4. A second
      virus, Matulaitis, has been isolated from a concurrent case of "non-paralytic
      poliomyelitis" in the same area. Lesions produced in infant mice by the two
      agents show certain differences.

PMID- 15428585
TI  - Lesions caused in suckling mice by certain viruses isolated from cases of so
      called non-paralytic poliomyelitis and of pleurodynia.
AB  - A STUDY HAS BEEN MADE OF THE LESIONS PRODUCED IN SUCKLING MICE BY THE FOLLOWING
      VIRUSES: Powers, Matulaitis, DeMole, Kine, McCarthy, Conn. 5, Ohio R, High Point,
      WS No. 4, EMC, and Col. SK. Pathologic alterations have been found in myocardium,
      lungs, liver, pancreas, thymus, brain and spinal cord, adipose tissue, and
      skeletal muscles. A comparison of the lesions produced by the individual strains
      has disclosed certain differential features which are discussed in detail. Within
      the group of so called Coxsackie viruses, myositis has not proved to be a
      constant finding, and it may occur in suckling mice infected with other types of
      virus.

PMID- 15428586
TI  - Relative resistance to extinction of escape training and avoidance training.

PMID- 15428587
TI  - An experimental test of the selective principle of association of drive stimuli.

PMID- 15428588
TI  - Resistance to extinction as a function of the distribution of extinction trials.

PMID- 15428589
TI  - Transfer of discrimination training to a motor task.

PMID- 15428590
TI  - An empirical explanation of the skewness of the bowed serial position curve.

PMID- 15428591
TI  - A remote association explanation of the relative difficulty of learning nonsense
      syllables in a serial list.

PMID- 15428592
TI  - The relation of vernier and depth discriminations to field brightness.

PMID- 15428593
TI  - Visual 'normalization' near the vertical and horizontal.

PMID- 15428594
TI  - Influence of the preceding item in measurements of the noise-masked threshold by
      a modified constant method.

PMID- 15428595
TI  - Perceptual organization of materials as a factor influencing ease of learning and
      degree of retention.

PMID- 15428596
TI  - The action of various after-effects on response repetition.

PMID- 15428597
TI  - Psychomotor performance and distribution of practice.

PMID- 15428598
TI  - A compensatory effect in vocal responses to stimuli of low intensity.

PMID- 15428599
TI  - The destruction of the Muller-Lyer illusion in repeated trials: satiation
      patterns and memory traces.

PMID- 15428600
TI  - Shock therapy comes of age.

PMID- 15428601
TI  - Physicians and medicine in early Alachua County and Gainesville, Florida.

PMID- 15428602
TI  - A general practitioner's care of the prostate.

PMID- 15428603
TI  - Multiple small bowel intussusception.

PMID- 15428604
TI  - Venous thrombosis.

PMID- 15428605
TI  - Treatment of pelvic malignant disease.

PMID- 15428606
TI  - Visual and retinal complications of diabetes mellitus.

PMID- 15428607
TI  - Granuloma of the larynx following intratracheal anesthesia.

PMID- 15428608
TI  - 6n propyl thiouracil in thyrotoxicosis complicating pregnancy.

PMID- 15428609
TI  - Potassium retention in crab nerve.
AB  - Spectrophotometric determinations of the potassium content of small volumes of
      sea water brought into contact with crab nerves over half-hour intervals
      demonstrate (a) a continuous loss of potassium from the fibers while at rest in
      oxygen; (b) an appreciable increase in the leakage during anoxia; (c) a
      reabsorption of potassium during postanoxic recovery; and (d) a reduction in the
      amplitude of the anoxic and postanoxic changes in the presence of glucose.

PMID- 15428610
TI  - Unmedullated fibers originating in dorsal root ganglia.
AB  - The compound action potential of the unmedullated fibers arising from dorsal root
      ganglia, as recorded in cat skin nerves after conduction of simultaneously
      initiated impulses, shows among its components a temporal dispersion
      corresponding to velocities between 2.3 and 0.7 M.P.S. The maximum representation
      of the component velocities is at about 1.2 M.P.S. On both sides of the maximum
      the representation falls off irregularly, in such a way that groupings in the
      distribution produce in the action potential a configuration in which successive
      features appear always in the same positions at a given conduction distance.
      Through this demonstration of a characteristic configuration the system of the
      unmedullated fibers is brought into analogy with that of the medullated fibers.
      The unmedullated fibers originating in the dorsal root ganglia have distinctive
      physiological properties, among which is a large positive potential which reaches
      its maximum immediately after the spike and decrements to half relaxation in
      about 50 msec., at 37 degrees C. The positive phases of the unit potentials in
      the compound action potential, owing to their duration, sum to a much greater
      extent than the temporally dispersed spikes; and, since they have sizes such that
      one equivalent to 25 per cent of the spike height would not be at the limit, in
      the summation process the major portion of the compound action potential is
      caused to be written at a potential level positive to the starting base line. The
      position of the spikes in the sequence can be seen in the analyses in Section
      III. The course of the activity in unit fibers is subject to variation in ways
      affecting the positive potential. Preliminary descriptions, based on orienting
      experiments, of how these variations are conditioned are given in Section I. Two
      of the findings are particularly noteworthy. One is the high sensitivity of the
      dimensions of the postspike positivity to temperature in the range of
      temperatures at which skin nerves may be expected to function, even when the
      environmental temperatures of an animal are moderate. The other is the high
      sensitivity to conditioning by previous activity. The positivity is first
      decreased, then replaced by a negative potential of similar duration. Reasons
      have been given why it is inadvisable at the present time to call the postspike
      potential an after-potential. A comparison has been made of the properties of the
      unmedullated fibers arising from dorsal root ganglia with those of fibers arising
      from sympathetic ganglia. The differences are so great that, in the interest of
      precision in designation, a division of the C group of fibers into two subgroups
      is indicated. It is suggested that the two subgroups be named respectively d.r.C
      and s.C. Measurements have been made of the diameters of the d.r.C fibers in a
      saphenous nerve stained with silver. Graphs showing the number of fibers at each
      diameter are presented in Section II. In Section III there are shown
      constructions, from histological data, of the action potential as it would
      appear, after 3 cm. of conduction, with the correlation between diameter and
      velocity in strict linearity. The degree of fit between the constructed and
      recorded potentials can be seen in Fig. 18.

PMID- 15428611
TI  - Rate of potassium exchange of the human erythrocyte.
AB  - 1. The exchange of potassium by the human erythrocyte has been studied in vitro
      using radioactive potassium. 2. An incubation technique which maintains
      erythrocytes in an essentially normal state for over 48 hours was employed. 3.
      Exchange of radioactive potassium between the red cells and the extracellular
      fluid was regular and progressive, the specific activities of the intra- and
      extracellular fluids reaching equal values. This indicates that all the
      erythrocyte potassium is exchangeable and is exchanging at the same rate. 4. From
      these data, it was calculated that at 37 degrees C., 1.6 per cent of the
      erythrocyte potassium exchanges per hour, corresponding to an exchange of 1.5 mM
      of potassium per liter of red cells per hour. The time required for the exchange
      of 50 per cent of the red cell potassium is calculated to be 43 hours. 5. The
      temperature coefficient (Q(10)) of the potassium exchange rate is 2.2. This is
      the same as the temperature coefficient of the rate of utilization of glucose by
      the human erythrocyte. 6. Varying the percentage of red cells, plasma potassium
      concentration, initial glucose level, and pH between 7.0 and 7.7 had no effect on
      the potassium exchange rate.

PMID- 15428612
TI  - Cation exchange between cells and plasma of mammalian blood; methods and
      application to potassium exchange in human blood.
AB  - The exchange of potassium between cells and plasma of heparinized human blood has
      been studied in vitro using the radioactive isotope K(42). The changes in cell
      and plasma specific activity are characteristic of a simple two-compartment
      system. The mean of seven determinations of the exchange rate at 38 degrees C. is
      1.8 per cent of the cellular potassium per hour. The results indicate that at 38
      degrees C. the rate is relatively insensitive to oxygenation or reduction of the
      hemoglobin, and to 1200 r of gamma radiation. With varying temperature the rate
      follows pseudo first order kinetics with a Q(10) of 2.35. Below 15 degrees C. the
      rate of loss of potassium exceeds the rate of uptake.

PMID- 15428613
TI  - Effect of neurotomy on the inorganic cation content of skeletal muscle.
AB  - 1. A study of the effect of denervation on the inorganic cation content of muscle
      has been carried out. In this study 69 rats were employed. 2. By using the flame
      photometer for the estimation of sodium and potassium and increasing the
      sensitivity of previous methods for the estimation of calcium and magnesium, it
      has been possible to carry out analyses for all these ions on as little as 0.5
      gm. of tissue. 3. It was observed that following neurotomy the concentration of
      sodium and calcium in the whole muscle increased significantly while at the same
      time the potassium content decreased. The magnesium content remained unchanged
      during the period studied. 4. The significance of these results has been
      discussed.

PMID- 15428614
TI  - Drug and ion effects in frog muscle.
AB  - Procaine, cocaine, pyribenzamine, antistine, and phosphate decrease the uptake of
      water by frog sartorii in a Ringer solution in which potassium has been
      substituted for sodium; all but the last two leave the swelling in hypotonic
      Ringer practically unaltered. They also decrease the depolarizing action of
      potassium. These effects are considered indicative of reduced membrane
      permeability to potassium.

PMID- 15428615
TI  - Accumulation of potassium by human red cells.
AB  - 1. A method is described for measuring the accumulation of K at 37 degrees C. by
      washed human red cells in glucose-containing systems in which the pH is kept
      constant, the K content of the cells being compared with that of the cells of
      systems which contain no added glucose but which are otherwise treated similarly.
      2. In systems containing added glucose, the accumulation of K begins shortly
      after the cells have been warmed to 37 degrees C., proceeds to a maximum which is
      reached after about 10 hours, and then falls exponentially. The maximum rate of
      accumulation is found during the first 3 hours. In systems which contain no added
      glucose, the K content of the cells appears to decrease exponentially with time
      for about 18 to 24 hours; thereafter the K content of the cells may decrease
      rapidly and the systems may show considerable hemolysis. Sometimes a small
      accumulation effect is observed during the first 2 to 3 hours; this may be the
      result of the washed cells not having been completely freed of glucose. 3. The
      accumulation process proceeds at its maximum rate at pH 7.4 to 7.6, which is also
      the pH at which the K loss from the red cells is at a minimum in systems
      containing no added glucose. 4. When red cells are stored at 4 degrees C. for
      increasing lengths of time, the storage is accompanied by increasing K loss and
      the maximum rate of accumulation observed when the cells are warmed to 37 degrees
      C. at first becomes greater. If the storage at 4 degrees C. is continued for more
      than 3 to 4 days, the rate of the accumulation which occurs at 37 degrees C
      decreases again, the accumulation mechanism showing progressive deterioration
      with time even at low temperatures. This deterioration has a counterpart in the
      progressive deterioration (deduced from the analysis of the curves relating K
      content and time) of the accumulation mechanism with time at 37 degrees C. 5. The
      accumulation of K occurs at a maximum rate when the concentration of glucose in
      the system is between 50 and 200 mg./100 ml. Its temperature coefficient over the
      range 27-37 degrees C. is 2.4. In the presence of glucose and at pH 7.6,
      accumulation of K takes place from isotonic mixtures of KCl and LiCl or of KCl
      and CsCl only a little less actively than from mixtures of KCl and NaCl; i.e.,
      the accumulation of K under optimum conditions seems to be an active process
      which is at least partly independent of the excretion of Na.

PMID- 15428616
TI  - Aging of elastic tissue in human skin.

PMID- 15428617
TI  - Significance of medial age changes in the human pulmonary artery.

PMID- 15428618
TI  - Age changes in pupil size.

PMID- 15428619
TI  - Urinary neutral 17-ketosteroids in the aged.

PMID- 15428620
TI  - Stability of body function in the aged. I. Effect of exposure of the body to
      cold.

PMID- 15428621
TI  - Vitamin studies in middle-aged and old individuals. IV. Clinical studies in
      hypovitaminemia B1.

PMID- 15428622
TI  - Mortality in traumatic abdominal injuries in the elderly.

PMID- 15428624
TI  - The personal adjustment of recipients of old age assistance.

PMID- 15428623
TI  - A pasteboard leg prosthesis for elderly patients.

PMID- 15428625
TI  - Attitudes of superior groups towards retirement and old age.

PMID- 15428626
TI  - The medical organization of the modern home for the aged.

PMID- 15428627
TI  - Activities of the Finnish Gerontological Society.

PMID- 15428628
TI  - Dimorphic female blossom and fruit types on the same plant in Cucurbita pepo.

PMID- 15428629
TI  - Twin and triplet pepper seedlings; a study of polyembryony in Capsicum
      frutescence.

PMID- 15428630
TI  - Resuscitation of heat-inactivated seeds by X-radiation.

PMID- 15428631
TI  - A dwarf mutation in a nematode; a morphological mutant of Rhabditis briggsae, a
      free-living soil nematode.

PMID- 15428632
TI  - Evolution up to date.

PMID- 15428633
TI  - Factors affecting the propagation of Theiler's GDVII mouse encephalomyelitis
      virus in tissue cultures.

PMID- 15428634
TI  - A non-pathogenic bartonella-like organism developing in embryonate eggs after
      injection with Haemobartonella muris.

PMID- 15428635
TI  - A physiological study of virus parasitism. I. A method for determining the oxygen
      uptake of individual embryonated eggs.

PMID- 15428636
TI  - A physiological study of virus parasitism. II. The effect of environmental
      temperature on the rates of oxygen consumption of normal eggs and eggs infected
      with Newcastle disease virus.

PMID- 15428637
TI  - The zone of localization of antibodies VIII. Some properties of the antigen
      responsible for the renal localization of anti-kidney serum.

PMID- 15428638
TI  - Amino acids present in allantoic fluid proteins from chick embryos infected with
      influenza virus.

PMID- 15428639
TI  - Studies with the Rho (D) antigen.

PMID- 15428640
TI  - Chemotherapy of cancer with phosphotungstic acid-H2O2 and phosphomolybdic acid
      H2O2 preparations.

PMID- 15428641
TI  - Effect of penicillin on the bacterial contaminants of vaccine lymph.

PMID- 15428642
TI  - Blood matching for blood transfusion.

PMID- 15428643
TI  - Middle class diets.

PMID- 15428644
TI  - Scabies.

PMID- 15428646
TI  - A case of cystic lung.

PMID- 15428645
TI  - A case of valvular pneumothorax.

PMID- 15428647
TI  - Hypertension due to unilateral pyelonephritis.

PMID- 15428648
TI  - ARTIFICIAL insemination.

PMID- 15428650
TI  - SOME nonmedical obligations of physicians.

PMID- 15428649
TI  - DOCTOR makes a will.

PMID- 15428651
TI  - Determination of disability and impairment; general rules of procedure before the
      Industrial Board.

PMID- 15428652
TI  - The place of medical participant committees in the administration of the Medical
      Assistance Program.

PMID- 15428653
TI  - COUNTY departments; township trustees relationships; medical care.

PMID- 15428654
TI  - Experiment in socialized medicine tried by Indiana company; failed.

PMID- 15428655
TI  - INDIANA state medical association year book; membership roster.

PMID- 15428657
TI  - The differential diagnosis of jaundice.

PMID- 15428656
TI  - The acute abdomen.

PMID- 15428658
TI  - Hypertension.

PMID- 15428659
TI  - Use and abuse of the skin test in the diagnosis of chronic brucellar.

PMID- 15428660
TI  - Penicillin in acute rheumatic fever; case reports.

PMID- 15428661
TI  - Our country's rural health.

PMID- 15428662
TI  - My visit to Europe.

PMID- 15428663
TI  - The responsibility of American medicine.

PMID- 15428664
TI  - Mass casualties.

PMID- 15428665
TI  - Technical problems in the surgery of chronic duodenal ulcer.

PMID- 15428666
TI  - My experience with total gastrectomy.

PMID- 15428667
TI  - Experimental induction of acute gastric ulcers with histamine in beeswax.

PMID- 15428668
TI  - A study based on 41 years of thyroid surgery.

PMID- 15428669
TI  - Meckel's diverticulum; a study of 50 cases.

PMID- 15428670
TI  - Duodenal obstruction.

PMID- 15428671
TI  - Prolonged postanesthetic depression and apnea attributed to deca-methylene-bis
      (trimethylammonium bromide).

PMID- 15428672
TI  - Nitrofurazone in skin grafting.

PMID- 15428673
TI  - The resection-angulation operation for arthritis and ankylosis of the hip.

PMID- 15428674
TI  - The use of anticoagulants in small hospitals.

PMID- 15428675
TI  - Contributions to the therapy of the varicose complex.

PMID- 15428676
TI  - Polyposis of the colon.

PMID- 15428677
TI  - A new surgical treatment for keratoconus.

PMID- 15428678
TI  - Congenital atresia of the duodenum; report of two cases.

PMID- 15428680
TI  - Osteochondritis dissecans of the elbow.

PMID- 15428679
TI  - Reticuloendothelial hyperplasia of bone; report of a case of Letterer-Siwe's
      disease.

PMID- 15428681
TI  - Surgical consideration of intraspinal tumors.

PMID- 15428682
TI  - Surgery of the painful kidney.

PMID- 15428683
TI  - The clinical course in thirty-five cases of renal neoplasm.

PMID- 15428684
TI  - Complications in the urinary tract following left colonic operations.

PMID- 15428685
TI  - Chronic stenosing tenovaginitis of the wrist.

PMID- 15428686
TI  - Changing concepts concerning diverticulitis.

PMID- 15428688
TI  - Acute peritonitis; treatment of the pathologic process and its immediate
      aftermath; further experiences with plication.

PMID- 15428687
TI  - Lesions of the small intestine.

PMID- 15428689
TI  - Rupture of the pectoralis major muscle; review of the literature and report of
      two cases.

PMID- 15428690
TI  - Ectopic spleen with twisted pedicle; report of a case.

PMID- 15428691
TI  - Placenta accreta.

PMID- 15428692
TI  - Diagnosis of carcinoma of the lung.

PMID- 15428693
TI  - A new repair for umbilical hernia.

PMID- 15428694
TI  - Roentgen diagnosis of subdiaphragmatic abscess.

PMID- 15428695
TI  - Postoperative psychosis.

PMID- 15428696
TI  - Fibrin closure in surgery of the eye.

PMID- 15428697
TI  - Value and results of combined electrocoagulation and radium treatment in cancer
      of the rectum.

PMID- 15428698
TI  - Fibromyoma of the uterine cervix.

PMID- 15428699
TI  - A study of some antihistamine compounds by histamine iontophoresis 1.
      observations on the dose response.

PMID- 15428700
TI  - Preliminary note on the treatment of creeping eruption by electrolysis.

PMID- 15428701
TI  - Demonstration of the LE cell in the absence of anticoagulant.

PMID- 15428702
TI  - Failure of adenosine-5-monophosphate to affect favorably pruritus of atopic
      dermatitis.

PMID- 15428703
TI  - A statistical study and consideration of endocrine influences.

PMID- 15428704
TI  - Lichenoid tuberculid; a clinical and histopathologic study.

PMID- 15428705
TI  - Aureomycin in the treatment of granuloma inguinale and lymphogranuloma venereum.

PMID- 15428706
TI  - The intermediate zone (immune, refractory, anemic, depigmented zone); a
      preliminary investigation.

PMID- 15428707
TI  - The response of the sweat glands to some locally acting agents in human subjects.

PMID- 15428708
TI  - Studies in the allergy of infection; II. histologic responses of the skin to BCG
      vaccination in various categories of tuberculin sensitivity.

PMID- 15428709
TI  - The biological significance of the roentgen.

PMID- 15428710
TI  - Ragweed pollinosis; some practical considerations.

PMID- 15428711
TI  - What the general practitioner should know about bronchiectasis.

PMID- 15428712
TI  - Experience with extraperitoneal cesarean section in private practice.

PMID- 15428713
TI  - The management of clefts of the lip and palate.

PMID- 15428714
TI  - Erythroblastosis fetalis affecting one twin; case report.

PMID- 15428715
TI  - Mercy Hospital clinicopathologic conference; meningioma.

PMID- 15428716
TI  - Allergy in the general practice of medicine.

PMID- 15428717
TI  - Nasal allergy.

PMID- 15428718
TI  - The status of antihistamine therapy.

PMID- 15428719
TI  - Tonsillectomy and poliomyelitis, southwestern Iowa, 1948-49.

PMID- 15428720
TI  - Centenary of the Iowa State Medical Society.

PMID- 15428721
TI  - REVIEW of recent activities of the Division of Tuberculosis Control.

PMID- 15428722
TI  - MATERNAL mortality in the United States and in Iowa.

PMID- 15428723
TI  - The peril of the sun worshipper.

PMID- 15428724
TI  - The use of protein bound iodine as a clinical tool.

PMID- 15428725
TI  - The surgical treatment of patent ductus arteriosus.

PMID- 15428726
TI  - CARE of hand injuries; fractures and dislocations.

PMID- 15428727
TI  - CASE reports from the University of Kansas Medical Center; tumor conference.

PMID- 15428728
TI  - A comparative study of human cutaneous reactivity to thiomerin and other
      mercurial diuretics.

PMID- 15428729
TI  - The effects of the hypophysis, thyroid, sex steroids, and the adrenal cortex upon
      granulation tissue.

PMID- 15428730
TI  - Experience with the new anticoagulant, B.O.E.A.

PMID- 15428731
TI  - Sternal marrow puncture: the dilution with peripheral blood as determined by P32
      labeled red blood cells.

PMID- 15428732
TI  - The separation of the formed elements of whole blood by means of fraction I.

PMID- 15428733
TI  - Tracer iron distribution studies in irradiated rats with lead shielded spleens.

PMID- 15428734
TI  - The zinc turbidity test and its clinical application.

PMID- 15428735
TI  - Further studies of the effect of ergonovine on the coronary circulation.

PMID- 15428736
TI  - Activation and action of the fibrinolytic human blood plasma fractions.

PMID- 15428737
TI  - Studies on a case of acute antithromboplastinemia.

PMID- 15428738
TI  - Antimicrobial properties of neomycin.

PMID- 15428739
TI  - Blood levels and urinary excretion of aureomycin after intravenous and
      intramuscular administration.

PMID- 15428740
TI  - The effect of methylene blue on established alloxan diabetes.

PMID- 15428741
TI  - A comparison of the effect of voluntary hyperventilation in normal persons,
      patients with pulmonary emphysema, and patients with cardiac disease.

PMID- 15428742
TI  - Limited usefulness of male amphibia for pregnancy tests.

PMID- 15428743
TI  - Estimation of increased gamma globulin and fibrinogen in cerebrospinal fluid; a
      serial dilution-flocculation method.

PMID- 15428744
TI  - Danger of false results using screw-capped tubes in diagnostic bacteriology.

PMID- 15428745
TI  - The quantitative estimation of Bence Jones proteins in urine.

PMID- 15428746
TI  - A direct writing, six channel oscillograph.

PMID- 15428747
TI  - An apparatus for pipetting radioactive solutions.

PMID- 15428748
TI  - Modification of Scholander's apparatus for the determination of carbon dioxide in
      blood plasma.

PMID- 15428749
TI  - A cylinder-plate assay for chloromycetin in body fluids and tissue extracts.

PMID- 15428750
TI  - A direct-writing pneumotachograph.

PMID- 15428751
TI  - Effect of prolonged storage at 4 to 5 degree C. on the neutralizing antibody of
      antiserum against poliomyelitis virus.

PMID- 15428752
TI  - Coronary artery disease in young adults; etiology and pathogenesis.

PMID- 15428753
TI  - The role of x-ray therapy in carcinoma of the breast.

PMID- 15428754
TI  - John Charnley McKinley, 1891-1950.

PMID- 15428755
TI  - The treatment of congenital clubfeet with wedging casts.

PMID- 15428756
TI  - Recent poliomyelitis experience in Minnesota.

PMID- 15428757
TI  - Ophthalmic headache; a differential study.

PMID- 15428758
TI  - A preliminary report of twenty patients treated with delta 5 pregnenolone and
      remissions in rheumatoid arthritis following gold therapy.

PMID- 15428759
TI  - Treatment of pruritus ani, vulvae et scroti.

PMID- 15428760
TI  - The American College Health Association, its progress, problems and prospects.

PMID- 15428761
TI  - The place of health education in a college health program.

PMID- 15428762
TI  - The neurosurgical treatment of intractable pain.

PMID- 15428763
TI  - Narco-analysis for criminal interrogation; a preliminary report.

PMID- 15428764
TI  - Group therapy in a child guidance clinic.

PMID- 15428765
TI  - Antihistaminic prophylaxis and treatment of respiratory infections.

PMID- 15428766
TI  - Madura foot or mycetoma pedis.

PMID- 15428767
TI  - Clinical use of a new subcutaneous mercurial diuretic, thiomerin.

PMID- 15428768
TI  - Relief of anal pain; a preliminary report.

PMID- 15428769
TI  - Metastatic renal malignancy.

PMID- 15428770
TI  - The use of penicillin in the management of chickenpox at the college age level; a
      preliminary report.

PMID- 15428771
TI  - Important factors in the epidemiology of tuberculosis.

PMID- 15428772
TI  - Positional nystagmus; a review and future prospects.

PMID- 15428774
TI  - Shakespeare on the ear, nose and throat.

PMID- 15428773
TI  - On the treatment of otogenic brain abscesses.

PMID- 15428775
TI  - Record of three cases of rhinoscleroma in Iraq.

PMID- 15428776
TI  - A development of the peep-show audiometer.

PMID- 15428777
TI  - Incidence, diagnosis and treatment of diabetes mellitus.

PMID- 15428778
TI  - Causes of blindness in Maine.

PMID- 15428779
TI  - Common hand injuries.

PMID- 15428780
TI  - Replacement therapy and fluid equilibrium.

PMID- 15428782
TI  - General reactions following the use of aureomycin in the eye.

PMID- 15428781
TI  - Some allergies of the gastrointestinal tract.

PMID- 15428783
TI  - WHAT every Maine doctor should know about the defense against the atomic bomb.

PMID- 15428784
TI  - [Endoscopic data on bronchitis with special note on the early diagnosis of cancer
      of the bronchi].

PMID- 15428785
TI  - [Indications and role of bronchoscopy in broncho-pulmonary tuberculosis].

PMID- 15428786
TI  - [Bronchoscopy in dyspnea].

PMID- 15428787
TI  - [Pulmonary or myocardial infarct?].

PMID- 15428788
TI  - [Myeloma and duodenal ulcer].

PMID- 15428789
TI  - [Acephalic monster and twin pregnancy].

PMID- 15428790
TI  - [Epidural staphylococcic abscess].

PMID- 15428791
TI  - [Tuberculous peritonitis in the aged].

PMID- 15428792
TI  - [False appendicitis and painful abdominal manifestations in primary tuberculosis
      infections].

PMID- 15428793
TI  - [Whooping cough lung and whooping cough mediastinitis].

PMID- 15428794
TI  - [Therapeutic indications of penicillin-streptomycin association].

PMID- 15428795
TI  - [What every doctor should know about strabismus in children].

PMID- 15428796
TI  - [Ocular manifestations in closed head wounds; their diagnostic value].

PMID- 15428797
TI  - [Diagnostic value of modifications of the pupils in diseases of the nervous
      system].

PMID- 15428798
TI  - [Coagulant and anticoagulant therapy].

PMID- 15428799
TI  - [Modern pathogenic classification of essential anemias due to dyshematopoiesis].

PMID- 15428800
TI  - [Study of hemolytic anemias].

PMID- 15428801
TI  - Survey of modern physical methods of treatment for mental illness carried out in
      Grangegorman Mental Hospital.

PMID- 15428802
TI  - The diseases of adaptation as revealed by cortisone and ACTH.

PMID- 15428803
TI  - Presidential address; delivered at the annual general meeting, July 5th, 1950.

PMID- 15428804
TI  - The common anaemias.

PMID- 15428805
TI  - Some laboratory aspects of the common anaemias.

PMID- 15428806
TI  - Burns; their effects and treatment.

PMID- 15428807
TI  - Use of the oral mercurial diuretics in advanced congestive heart failure.

PMID- 15428808
TI  - The injection treatment of hemorrhoids.

PMID- 15428810
TI  - Endometriosis: the urgency for early diagnosis and treatment.

PMID- 15428809
TI  - The significance of nipple discharge.

PMID- 15428812
TI  - The clinical implications of the Rh factor.

PMID- 15428811
TI  - The routine use of exfoliative cytologic examinations for the detection of
      asymptomatic cancer of the cervix uteri.

PMID- 15428813
TI  - Edward Campbell Davis, M. D., 1867-1931.

PMID- 15428814
TI  - Biologic activities of the Georgia Typhus Control Program.

PMID- 15428815
TI  - Today's indications for cesarean section.

PMID- 15428816
TI  - The diagnosis of obstructive lesions of the gastrointestinal tract of the newborn
      infant.

PMID- 15428817
TI  - Diagnosis and early management of acute poliomyelitis.

PMID- 15428818
TI  - Rehabilitation of the crippled child.

PMID- 15428819
TI  - Treatment of flat feet in children.

PMID- 15428820
TI  - Granuloma of ileocecal region; need for study of fresh surgical specimen; a case
      report.

PMID- 15428821
TI  - Spontaneous pneumothorax.

PMID- 15428822
TI  - The Jefferson-Hillman Hospital.

PMID- 15428823
TI  - Hysterectomy; indications, technique and results.

PMID- 15428824
TI  - Fluid and electrolyte therapy.

PMID- 15428825
TI  - The diagnosis and management of subdural hematoma in infants.

PMID- 15428826
TI  - "Then conquer we must-"; the Elias J. Marsh Oration.

PMID- 15428827
TI  - Primary carcinoma of the trachea simulating bronchial asthma.

PMID- 15428828
TI  - Obstetrical responsibility in neonatal deaths.

PMID- 15428829
TI  - Significance of rectal bleeding.

PMID- 15428830
TI  - Malignancy of the thyroid.

PMID- 15428831
TI  - Hypersensitiveness to insulin.

PMID- 15428832
TI  - Blood procurement.

PMID- 15428833
TI  - The problem of endometriosis.

PMID- 15428834
TI  - Early diagnosis of carcinoma of the breast by cytologic technic; with report of a
      case.

PMID- 15428835
TI  - The cancer problem.

PMID- 15428836
TI  - An operation for non-specific allergic rhinitis.

PMID- 15428837
TI  - Immediate treatment of barbiturate poisoning; use of electrostimulatory therapy.

PMID- 15428838
TI  - Pregnancy complicated by subarachnoid hemorrhage; case report.

PMID- 15428839
TI  - Vertigo.

PMID- 15428840
TI  - Occupational dermatoses.

PMID- 15428841
TI  - Carbon monoxide detection in routine blood examinations.

PMID- 15428842
TI  - Management of hyperthyroidism.

PMID- 15428843
TI  - Left hepato-jejunostomy for biliary obstruction, with case report.

PMID- 15428844
TI  - Role of the gastroscopist in diagnosis.

PMID- 15428845
TI  - Spontaneous rupture of the heart.

PMID- 15428846
TI  - Murine (endemic) typhus in New Jersey; report of a case.

PMID- 15428847
TI  - Why not x-ray before marriage?

PMID- 15428848
TI  - Trends in gynecology and obstetrics.

PMID- 15428849
TI  - Preventive pediatrics.

PMID- 15428850
TI  - Management of diarrheas of infancy and childhood.

PMID- 15428851
TI  - Differentiation of anorexia nervosa and pituitary cachexia; case report.

PMID- 15428852
TI  - The treatment of acute otitis media.

PMID- 15428853
TI  - The hospital management of gall-bladder disease.

PMID- 15428854
TI  - The therapy of non-tuberculous urinary tract infections.

PMID- 15428855
TI  - Bronchoscopy as an aid in the diagnosis of chest lesions.

PMID- 15428856
TI  - Laboratory methods for the diagnosis of malignancies.

PMID- 15428857
TI  - In retrospect: changing attitude of the medical profession.

PMID- 15428858
TI  - Gaucher's disease; discussion and case presentation.

PMID- 15428859
TI  - Benadryl in the treatment of Parkinson's syndrome.

PMID- 15428860
TI  - Potassium in electrolyte balance.

PMID- 15428861
TI  - Paralysis of distal jejunal loop after partial gastrectomy; an unusual
      complication of gastrectomy.

PMID- 15428862
TI  - Emotional attitudes of infants.

PMID- 15428863
TI  - Advantages of a uniform infant formula.

PMID- 15428864
TI  - Advanced abdominal pregnancy; case report.

PMID- 15428865
TI  - Treatment of perforated peptic ulcer in a general hospital; statistical analysis.

PMID- 15428866
TI  - Bronchial obstruction due to endobronchial lesions.

PMID- 15428867
TI  - Comparison of mercurial diuretics and routes of administration with special
      reference to thiomerin.

PMID- 15428868
TI  - Manual removal of the placenta.

PMID- 15428869
TI  - Head injury; its common sense treatment.

PMID- 15428870
TI  - Federal aid through grants-in-aid and subsidies.

PMID- 15428871
TI  - Adrenalin-producing tumors arising from pheochrome tissue: their clinical
      manifestations, diagnosis, and treatment.

PMID- 15428872
TI  - CLINICAL pathologic conference; bronchiectasis; amyloidosis; thyroiditis with
      lower nephron nephrosis.

PMID- 15428873
TI  - Mucocele of the appendix.

PMID- 15428874
TI  - Xanthomatoses; physiology of cholesterol metabolism in man.

PMID- 15428875
TI  - An ultraviolet spectrophotometric method for the determination of delta 3,5
      androstadienone-17 in the urine.

PMID- 15428876
TI  - The role of antibodies in insulin resistance; report of a case.

PMID- 15428877
TI  - Hodgkin's disease localized to the anterior mediastinum: clinical, roentgen and
      surgical considerations.

PMID- 15428878
TI  - Hemangioma of the pons; case report and review of the literature.

PMID- 15428879
TI  - Inspiratory increase of the pulse amplitude, its relation to pulsus paradoxus.

PMID- 15428880
TI  - Restored viability of implanted preserved necrocartilage in rhinoplasty.

PMID- 15428881
TI  - Orthodigital technique in the treatment of chiropodical lesions.

PMID- 15428882
TI  - Professional relations.

PMID- 15428883
TI  - Nail plate penetrability, a report.

PMID- 15428884
TI  - Foot defects as possible etiological factors in cancer.

PMID- 15428885
TI  - Wound healing.

PMID- 15428886
TI  - New methods of muscular regeneration for equilibrium by electrotherapy.

PMID- 15428887
TI  - The treatment of bone and joint tuberculosis with surgery and streptomycin.

PMID- 15428888
TI  - Psychosurgery.

PMID- 15428889
TI  - Some surgical principles in hemipelvectomy.

PMID- 15428890
TI  - Notes on the British Health Plan.

PMID- 15428891
TI  - Solitary kidney complicated by congenital uretero-pelvic obstruction; two cases.

PMID- 15428892
TI  - Medical group practice.

PMID- 15428893
TI  - Omphalocele.

PMID- 15428894
TI  - Primary repair of parotid duct injuries.

PMID- 15428895
TI  - Needs for hospital facilities and physicians in thirteen southern states.

PMID- 15428896
TI  - Charles Richard Drew, M. D., 1904-1950.

PMID- 15428897
TI  - Cutaneous thresholds for pain before and after unilateral prefrontal lobotomy;
      preliminary report.

PMID- 15428898
TI  - Emotions induced and studied in hypnotic subjects. Part II: The findings.

PMID- 15428899
TI  - Disturbances in time discrimination in organic brain disease.

PMID- 15428900
TI  - Lower nephron nephrosis following electroconvulsive therapy; report of 2
      fatalities.

PMID- 15428901
TI  - Psychoneurotic veterans in industry.

PMID- 15428902
TI  - Benadryl and theophorin in the treatment of advanced parkinsonism.

PMID- 15428903
TI  - Morbid hunger of cerebral origin.

PMID- 15428904
TI  - Conservative surgical therapy of brain abscesses.

PMID- 15428905
TI  - Amino acid supplementation of proteins and protein hydrolysates.

PMID- 15428906
TI  - Manganese deficiency in rats with relation to ataxia and loss of equilibrium.

PMID- 15428907
TI  - Self selection of diet; XII. Effects of B vitamin deficiencies on selection of
      food components.

PMID- 15428908
TI  - The arginine and histidine content of meats.

PMID- 15428909
TI  - Hypervitaminosis A in the rat.

PMID- 15428910
TI  - Congenital anomalies in the chick due to vitamin B12 deficiency.

PMID- 15428911
TI  - The effect of phytate and other food factors on iron absorption.

PMID- 15428912
TI  - Observations on niacin, riboflavin, allantoin, ascorbic acid, and vitamin A
      during anabolism induced by hormones.

PMID- 15428913
TI  - Observations on the prolonged feeding to rats of the flour maturing agent,
      ammonium persulfate.

PMID- 15428914
TI  - The effect of fat level of the diet on general nutrition. VI. The interrelation
      of linoleate and linolenate in supplying the essential fatty acid requirement in
      the rat.

PMID- 15428915
TI  - A quantitative estimation of the effect of rutin on the biological potency of
      vitamin C.

PMID- 15428916
TI  - The effects of excess tryptophan and excess lysine on the production of rickets
      in the rat.

PMID- 15428917
TI  - Some aspects of chorion epithelioma.

PMID- 15428918
TI  - The role of the tumour bed in the treatment of squamous-cell cancers by
      irradiation.

PMID- 15428919
TI  - The pathology of malignant ovarian tumours.

PMID- 15428920
TI  - The extent of breast feeding in Great Britain in 1946, with special reference to
      the health and survival of children.

PMID- 15428921
TI  - The ovarian theca cell.

PMID- 15428922
TI  - On the structure of the human placenta with full-time and immature foetus, living
      or dead.

PMID- 15428923
TI  - A report on 1,051 consecutive cases of abdominal hysterectomy in which a
      technique using a continuous suture only was used in securing the pedicles.

PMID- 15428924
TI  - Round ligament sling operation for stress incontinence.

PMID- 15428925
TI  - A case of cystadenofibroma of ovary.

PMID- 15428926
TI  - The future in the treatment of carcinoma of the cervix.

PMID- 15428927
TI  - An outbreak of pemphigus neonatorum in the maternity department of a general
      hospital: with special reference to the source of infection.

PMID- 15428928
TI  - Primary rupture of the upper membranes in twin labour.

PMID- 15428929
TI  - A case of haemangioma of the uterus.

PMID- 15428930
TI  - An unusual lesion probably of a granulomatous nature occurring in the skin of a
      newborn child.

PMID- 15428931
TI  - Vaginitis emphysematosa.

PMID- 15428932
TI  - Two cases of dysgerminoma ovarii, one occurring in a malignant teratoma in
      association with acute myelocytic leukaemia.

PMID- 15428933
TI  - Five cases of chorioangioma.

PMID- 15428935
TI  - Genital abnormalities in 2 sisters.

PMID- 15428934
TI  - Volvulus of the caecum and pre-eclampsia complicating labour.

PMID- 15428936
TI  - A mixed dermoid and granulosa-cell tumour.

PMID- 15428937
TI  - A case of foreign body in the abdominal wall fourteen years after hysterectomy.

PMID- 15428938
TI  - An unusual ovarian complication of pregnancy.

PMID- 15428939
TI  - A case of ureteric obstruction following colporrhaphy.

PMID- 15428940
TI  - Some queries regarding sterility investigations.

PMID- 15428941
TI  - Selection of blood donors.

PMID- 15428942
TI  - Parasitic diseases and problems in diagnosis.

PMID- 15428944
TI  - The treatment of clubfoot.

PMID- 15428943
TI  - Dangerous post-partum blood loss from first degree lacerations.

PMID- 15428945
TI  - Infantile cortical hyperostoses.

PMID- 15428946
TI  - Vasomotor rhinitis.

PMID- 15428947
TI  - A psychiatric test for general practice; clinical applications.

PMID- 15428948
TI  - Virus eye diseases.

PMID- 15428949
TI  - Therapeutic uses of the vitamins B.

PMID- 15428950
TI  - Adrenal insufficiency in infancy; a clinical classification, review, and a report
      of a case.

PMID- 15428951
TI  - Use of chloromycetin in infections. I. In nonbacterial (atypical
      undifferentiated) respiratory infections.

PMID- 15428952
TI  - Use of chloromycetin in infections.

PMID- 15428953
TI  - Influenzal meningitis treated with chloromycetin; a preliminary report.

PMID- 15428954
TI  - Report of a case of influenzal meningitis treated with polymyxin B (aerosporin).

PMID- 15428955
TI  - Coarctation of the aorta in early infancy.

PMID- 15428956
TI  - Prothrombin in the newborn infant. V. Further observations on the nature of
      prothrombin in the newborn infant: comparative effect of storage on prothrombin
      of the newborn infant and normal adult.

PMID- 15428957
TI  - Prothrombin in the newborn infant. VI. Effect of sulfadiazine on prothrombin of
      the newborn infant.

PMID- 15428958
TI  - Congenital thrombocytopenic purpura of the newborn infant; report of a case.

PMID- 15428959
TI  - Spontaneous hemorrhage from a hemangioma of the pons.

PMID- 15428960
TI  - Congenital absence of the external genitals; persistent primitive cloaca.

PMID- 15428961
TI  - Multiple intestinal obstruction in a newborn infant with recovery.

PMID- 15428962
TI  - Newer knowledge on the pathogenesis of poliomyelitis.

PMID- 15428963
TI  - Diagnostic value of three drawing tests for children.

PMID- 15428964
TI  - A basic classification of "gingival enlargement".

PMID- 15428965
TI  - The rationale of pocket elimination in the treatment of periodontal disease.

PMID- 15428966
TI  - Some recent concepts of the connective tissue ground substance and their
      implications in dental disease.

PMID- 15428967
TI  - Occurrence of gingivitis in suburban Chicago school children.

PMID- 15428968
TI  - The etiology of periodontal disease: a review of current literature.

PMID- 15428969
TI  - Interaction processes and personal codification.

PMID- 15428970
TI  - The warm-cold variable in first impressions of persons.

PMID- 15428971
TI  - The relation of somatotype to self-ratings on Sheldon's tempermental traits.

PMID- 15428972
TI  - The relation of somatotype to reaction time, resistance to pain, and expressive
      movement.

PMID- 15428973
TI  - A measure of personality integration in relation to the concept of self.

PMID- 15428974
TI  - Investigations into the 'self-concept'; the W-A-Y technique.

PMID- 15428975
TI  - [Analytic study of PAS and the product of its decarboxylation; use of various
      methods in analyzing different pharmaceutical preparations].

PMID- 15428976
TI  - [Not Available].

PMID- 15428977
TI  - [Inadequate standards for ampule glass set by the Pharm. Brit. IV].

PMID- 15428978
TI  - [Value of chromatography in the analysis of medications].

PMID- 15428979
TI  - Re-evaluation of the effectiveness of pentamethylenetetrazol (metrazol) as an
      analeptic agent during thiopental depression.

PMID- 15428980
TI  - The influence of drugs on the irritability and automaticity of heart muscle.

PMID- 15428981
TI  - Energy metabolism of rabbit intestine as influenced by metabolic blocking agents.

PMID- 15428982
TI  - The action of sodium fluoroacetate on intestinal smooth muscle.

PMID- 15428983
TI  - The influence of diphenhydramine HCl (benadryl) on apomorphine-induced emesis in
      dogs.

PMID- 15428984
TI  - Relationship of chemical structure to antifibrillatory potency of certain alpha
      fagarine like compounds.

PMID- 15428985
TI  - Pharmacological study and clinical use of an alaphfagarine like compound (N
      methyl)-N-(3,4, dimethoxy benzyl)-beta-(4 methoxyphenyl)-ethylamine-HCl.

PMID- 15428986
TI  - Liver cell alteration and DDT storage in the fat of the rat induced by dietary
      levels of 1 to 50 p.p.m. DDT.

PMID- 15428987
TI  - A pharmacologic and toxicologic study of heptyl aldehyde sodium bisulfite
      (hepbisul).

PMID- 15428988
TI  - Curare-like action of decamethylene-bis(atropinium iodide).

PMID- 15428989
TI  - The action of 4-amino-N10-methyl-pteroylglutamic acid in mice, rats, and dogs.

PMID- 15428990
TI  - The comparative pharmacology of the isomeric chain methyl substituted
      heptylamines.

PMID- 15428991
TI  - Studies on heptazone (6-morpholino-4,4-diphenyl-3-heptanone hydrochloride) in
      comparison with other analgesic drugs.

PMID- 15428992
TI  - Evaluation of curarizing drugs in man. Potency, duration of action, and effects
      on vital capacity of D-tubocurarine, dimethyl-D-tubocurarine, and decamethylene
      bis (trimethylammonium bromide).

PMID- 15428993
TI  - The effect of ferrous iron of pupillary reactions.

PMID- 15428994
TI  - Local emetic activity of glycosides of the digitalis series.

PMID- 15428995
TI  - Comparative increase in ventricular contractile force produced by several cardiac
      glycosides.

PMID- 15428996
TI  - Effect of convulsant and anticonvulsant agents on the activity of oxalacetic and
      pyruvic carboxylase.

PMID- 15428997
TI  - The tolerance of the dog under thiopental sodium anesthesia to high
      concentrations of carbon dioxide.

PMID- 15428998
TI  - Phosphorylated intermediates of chronically and acutely morphinized rats.

PMID- 15428999
TI  - Studies on the distribution and metabolism of methadone in normal and tolerant
      rats by a new colorimetric method.

PMID- 15429000
TI  - Effect of tridione (3,3,5-trimethloxazolidine-2,4-dione) on the oxygen uptake of
      mouse brain.

PMID- 15429001
TI  - Observations on the role of the adrenal medulla in the blood pressure response to
      nicotine.

PMID- 15429002
TI  - Studies on diethylaminoethanol. II. Antiarrhythmic activity in two homologous
      alcohol series.

PMID- 15429003
TI  - Studies of the toxic action of gallium.

PMID- 15429004
TI  - A comparison of several dose-action curves for the pressor action of epinephrine.

PMID- 15429005
TI  - Studies on veratrum alkaloids. XII. A quantitative comparison of the
      antiaccelerator cardiac action of veratramine, veratrosine, jervine and pseudo
      jervine.

PMID- 15429006
TI  - Effects of methadone and morphine of the electroencephalogram of the dog.

PMID- 15429007
TI  - Pharmacology and toxicology of antibiotics.

PMID- 15429008
TI  - Ganglionic blocking agents.

PMID- 15429009
TI  - Pharmacology of the neuromuscular junction.

PMID- 15429010
TI  - Theories of general anesthesia.

PMID- 15429011
TI  - Mechanism of action and therapeutic use of diuretics.

PMID- 15429012
TI  - The effect of sodium fluoroacetate on the contractility and metabolism of
      intestinal smooth muscle.

PMID- 15429013
TI  - Pharmacological properties of some neostigmine analogs.

PMID- 15429014
TI  - Changes in renal function produced by morphine in normal dogs and dogs with
      diabetes insipidus.

PMID- 15429015
TI  - The levator ani muscle of the rat as an index of myotrophic activity of steroidal
      hormones.

PMID- 15429016
TI  - The pharmacologic action of some analogs of 1-(3,4-dihydroxyphenyl)-2-amino-1
      butanol (ethylnorepinephrine).

PMID- 15429017
TI  - Dehydroacetic acid (DHA). Acute and chronic toxicity.

PMID- 15429018
TI  - Dehydroacetic acid (DHA). General pharmacology and mechanism of action.

PMID- 15429019
TI  - Dehydroacetic acid (DHA). Estimation, absorption and distribution.

PMID- 15429020
TI  - Dehydroacetic acid (DHA). Detoxication and effects on renal function.

PMID- 15429021
TI  - Chronic oral toxicity of a high gel point methylcellulose (methocel HG) in rats
      and dogs.

PMID- 15429022
TI  - The effect of fluoroacetate on the sartorius muscle of the frog.

PMID- 15429023
TI  - Studies on veratrum alkaloids. Metabolic action of veratridine and of the
      secondary amine bases veratramine, veratrosine, and pseudo-jervine on cardiac
      tissue of the rat.

PMID- 15429024
TI  - Short-termporal toxicity tests of methoxychlor (2,2 di-(P-methoxy phenyl)-1,1,1
      trichlorethane) in rats and dogs.

PMID- 15429025
TI  - [Sterilization of the solutions to be injected].

PMID- 15429026
TI  - A note on the determination of alkaloids by exchange of ions.

PMID- 15429027
TI  - The influence of iodide concentration in the iodimetric titration of penicillin.

PMID- 15429028
TI  - Experiments on the toxicology of 2:3:5:6-tetrachloronitrobenzene.

PMID- 15429029
TI  - The comparative antibacterial activity of o-chloromercuriphenol and
      phenylmercuric acetate.

PMID- 15429030
TI  - The evaluation of the bactericidal activity of ethylene glycol and some of its
      mono-alkyl ethers against Bacterium coli. XI. Discussion and general inferences.

PMID- 15429031
TI  - Folic acid, vitamin B12 and anaemia. I. Chemical aspects.

PMID- 15429032
TI  - Studies on synthetic analgesics.

PMID- 15429033
TI  - The occurrence of methyl compounds in galenicals.

PMID- 15429034
TI  - The estimation of sodium gentisate in tablets and injections.

PMID- 15429035
TI  - The optical crystallographic properties of crystals formed with nitric acid from
      pethidine, nicotinamide and cinchophen.

PMID- 15429036
TI  - Corneal transplantation in the North General Hospital.

PMID- 15429037
TI  - Intestinal adsorbents as adjuncts to the chemotherapy of infectious infantile
      diarrheas.

PMID- 15429039
TI  - A proposed organization chart of the Bureau of Hospitals.

PMID- 15429038
TI  - Conventional management of bronchitis.

PMID- 15429040
TI  - The incidence of dermatophytosis of the feet among Filipino high school students.

PMID- 15429041
TI  - A case of cyclopean fetus with vestigial mouth, nose, and ears.

PMID- 15429042
TI  - Inaugural address.

PMID- 15429043
TI  - Role of radiology in the diagnosis and treatment of mediastinal tumors.

PMID- 15429044
TI  - The Philippine medicinal plants as materia medica for our medical practitioners.

PMID- 15429045
TI  - The practical therapeutics in pulmonary tuberculosis.

PMID- 15429046
TI  - Early syphilis in Manila.

PMID- 15429047
TI  - The elevation of the standard of medical education in the Philippines, the
      purpose of medical associations.

PMID- 15429048
TI  - Toxoplasmosis and sparganosis in native Filipinos; clinical reports.

PMID- 15429050
TI  - [Transverse axial stratigraphy in pathology of the mediastinum].

PMID- 15429049
TI  - [Cerebral angiography].

PMID- 15429051
TI  - [Contribution to the study of ensheathing periostosis].

PMID- 15429052
TI  - [Importance of bronchography in the study of abscesses of the lung].

PMID- 15429053
TI  - [Total condensing and hypertrophic osteopathy of a rib in a young boy].

PMID- 15429054
TI  - [Radiotherapy of venereal tumors of the dog].

PMID- 15429055
TI  - [A new case of a left diaphragmatic eventration of the diaphragm].

PMID- 15429057
TI  - [Practical and topographic considerations on thoracic tomography].

PMID- 15429056
TI  - [Direct measurements of doses of x-rays on the hypophysis of the cadaver in
      customary roentgenotherapeutic conditions].

PMID- 15429058
TI  - [Measure of the radiographic focal distance].

PMID- 15429059
TI  - [Role of tomography in the study of the temporomandibular joint].

PMID- 15429060
TI  - [The new tomograph with a spiral movement].

PMID- 15429061
TI  - [Radiological diagnosis of images of the upper part of the stomach].

PMID- 15429062
TI  - [Favorable evolution of osteitis fibrosa of the mandible under the influence of
      radiotherapy].

PMID- 15429063
TI  - [Adamantine epithelioma treated after 20 years by radio-surgery].

PMID- 15429064
TI  - [Contact radiotherapy].

PMID- 15429065
TI  - [Contact radiotherapy in epitheliomas of the auricle of the ear].

PMID- 15429066
TI  - [Chronic vertebral osteomyelitis].

PMID- 15429067
TI  - [Radiological study of prognathism in the Berbers and the Arabs].

PMID- 15429068
TI  - [Congenital stricture of the aortic isthmus].

PMID- 15429069
TI  - [Radiological study of esophageal varices].

PMID- 15429071
TI  - [Two cases of cervical localization of Baastrup disease].

PMID- 15429070
TI  - [Two cases of reduction of intestinal invagination by barium lavage].

PMID- 15429072
TI  - [Acute case of labile cystic emphysema of the lung].

PMID- 15429073
TI  - [Three observations of cerebral arteriography].

PMID- 15429074
TI  - [Numerical data in tomography; enlargement ratio and index of sweep].

PMID- 15429075
TI  - [Large bulla of obstructive emphysema of the right lung during aneurysm of the
      aortic cross].

PMID- 15429076
TI  - [Radiology of the heart by systolic-diastolic double exposure].

PMID- 15429077
TI  - [Cineradiotherapy].

PMID- 15429078
TI  - [Cancer of the bladder and contact radiotherapy].

PMID- 15429079
TI  - [Study of different procedures in angiocardiography].

PMID- 15429080
TI  - [Tomography in thoracic malformations].

PMID- 15429081
TI  - [Primary cancer of the lung in infants].

PMID- 15429082
TI  - [Bronchographic signs of segmentary bronchitis].

PMID- 15429083
TI  - [Two cases of gastric diaphragmatic hernias associated with an anemic syndrome;
      the second case with an ulcer of the neck of the hernia].

PMID- 15429084
TI  - [So-called contact radiotherapy].

PMID- 15429085
TI  - [Horizontal crown cycloradiotherapy].

PMID- 15429087
TI  - The Cleveland Rehabilitation Center.

PMID- 15429086
TI  - What is rehabilitation?

PMID- 15429088
TI  - Symptoms of psychiatric disability.

PMID- 15429089
TI  - Fifty guests at Resthaven.

PMID- 15429090
TI  - Utilizing the handicapped in industry.

PMID- 15429091
TI  - Further experience with streptomycin in the treatment of tuberculous meningitis.

PMID- 15429092
TI  - Observations on the vitamin B2 complex deficiency syndrome in West African
      soldiers.

PMID- 15429093
TI  - Two uninary carriers of enteric group organisms presenting some interesting
      features.

PMID- 15429094
TI  - Some account of an operation in the Malayan jungle.

PMID- 15429095
TI  - Articles of food responsible for food poisoning in Egypt.

PMID- 15429096
TI  - Modern trends in the diagnosis and the treatment of congenital heart disease.

PMID- 15429097
TI  - The various types of food poisoning as they occur in Egypt.

PMID- 15429098
TI  - The effect of vitamin P on the metabolism of carbohydrates in diabetic and normal
      persons.

PMID- 15429099
TI  - Experimental study of gastrointestinal pain.

PMID- 15429100
TI  - Aneurysm of the splenic artery with a report of a case complicating Egyptian
      splenomegaly.

PMID- 15429101
TI  - The use of S. S. agar for the isolation of the causative organisms of food
      poisoning.

PMID- 15429102
TI  - A new synthetic drug with high oestrogenic potency.

PMID- 15429103
TI  - HEALTH Congress at Eastbourne, 24th-28th April, 1950.

PMID- 15429104
TI  - Inaugural address to the Health Congress at Eastbourne.

PMID- 15429105
TI  - Field epidemiology and the health service.

PMID- 15429106
TI  - Field epidemiology: the technical aspects.

PMID- 15429107
TI  - Field epidemiology and the health department: the practical aspects.

PMID- 15429108
TI  - Engineering and architecture; presidential address.

PMID- 15429109
TI  - Lighting of hospital and clinic buildings.

PMID- 15429111
TI  - Presidential address on ante-natal care.

PMID- 15429110
TI  - The use of colour in hospitals and clinics.

PMID- 15429112
TI  - Maternity services.

PMID- 15429113
TI  - The maternity service from the general practitioner aspect.

PMID- 15429114
TI  - The maternity service from the domiciliary midwife's point of view.

PMID- 15429115
TI  - Problems in the care and after-care of children exposed to tuberculous infection.

PMID- 15429116
TI  - Problems in the care and after-care of children exposed to tuberculous infection.

PMID- 15429117
TI  - Veterinary hygiene; presidential address.

PMID- 15429118
TI  - A scientific approach to meat inspection.

PMID- 15429119
TI  - Recent milk and dairies legislation and the provision of a safe milk supply.

PMID- 15429120
TI  - Food and nutrition; presidential address.

PMID- 15429121
TI  - Hygiene and food manufacture; the baking industry.

PMID- 15429122
TI  - Hygiene and food manufacture; factory hygiene in the canning industry.

PMID- 15429123
TI  - Hygiene and food manufacture; the meat products industry.

PMID- 15429124
TI  - Housing and town planning; presidential address.

PMID- 15429125
TI  - District heating.

PMID- 15429126
TI  - Planning in rural areas.

PMID- 15429127
TI  - [Pigmentary cirrhosis; a case of isolated pigmentary cirrhosis without
      melanoderma].

PMID- 15429128
TI  - [Frigidity; the neurotic reactions of the couple; therapy].

PMID- 15429129
TI  - [Chronic uremic nephritis improved by steroid hormones (desoxycorticosterone and
      testosterone); study of renal filtration-resorption].

PMID- 15429130
TI  - [Resection of diverticulum of the hypopharynx followed by a cicatricial kink of
      the esophagus; treatment by bouginage].

PMID- 15429131
TI  - [Not Available].

PMID- 15429132
TI  - What's wrong with the American family?

PMID- 15429133
TI  - Living with our children.

PMID- 15429134
TI  - WASHINGTON, D.C. considers sex offenses; how one community undertook to tell its
      citizens the facts about sex crimes and criminals, and what may be done to deal
      effectively with such problems.

PMID- 15429136
TI  - ONE Hundred and Second Annual Session of the South Carolina Medical Association.

PMID- 15429135
TI  - Sex crimes and the prostitution racket.

PMID- 15429137
TI  - Prenatal influences.

PMID- 15429138
TI  - Case report; plasma cell tumors of the paranasal sinuses: report of 2 cases.

PMID- 15429139
TI  - Nontraumatic intracranial hemorrhage.

PMID- 15429140
TI  - Honesty and courage can eradicate tuberculosis.

PMID- 15429141
TI  - Intrathoracic neurogenic tumors.

PMID- 15429142
TI  - Transthoracic approach for complete removal of the posterior mediastinal and
      intravertebral perineural fibroblastoma.

PMID- 15429143
TI  - Cholesterol pericarditis.

PMID- 15429144
TI  - A clinical and radiologic study of metastatic pulmonary neoplasms.

PMID- 15429145
TI  - High segmental spinal anesthesia; a preliminary report.

PMID- 15429146
TI  - Treatment of endobronchial tuberculosis with streptomycin.

PMID- 15429147
TI  - Cancer of the cervical esophagus; with a case report.

PMID- 15429148
TI  - The differential diagnosis of unresolved pneumonia and bronchiogenic carcinoma by
      pulmonary angiography.

PMID- 15429149
TI  - Excisional surgery in pulmonary coccidioidomycosis.

PMID- 15429150
TI  - Cystic accessory lobe.

PMID- 15429151
TI  - Rhabdomyosarcoma of the esophagus.

PMID- 15429152
TI  - Effectiveness of dromoran (3-hydroxyn-methyl morphinan) as an analgesic in
      thoracic surgery.

PMID- 15429153
TI  - Pulmonary histoplasmosis: review of published cases and report of an unusual
      case.

PMID- 15429154
TI  - Partial pericardiectomy in a case of hemopericardium due to nonpenetrating
      trauma.

PMID- 15429155
TI  - Pulmonary prosthesis after pneumonectomy.

PMID- 15429156
TI  - Unilateral loss of cough reflex following complete autonomic denervation of the
      lung for bronchial asthma.

PMID- 15429157
TI  - Metastatic pulmonary malignancy: a study of factors involved in exfoliation of
      malignant cells.

PMID- 15429158
TI  - Experiences with the use of direct aortography in the diagnosis of coarctation of
      the aorta.

PMID- 15429159
TI  - Arteriovenous fistula of the lung.

PMID- 15429160
TI  - The prevention of spread during pulmonary resection by the use of a double-lumen
      catheter.

PMID- 15429161
TI  - Considerable improvement following exploratory thoracotomy in two cases of
      tetralogy of Fallot.

PMID- 15429162
TI  - Resection of transverse processes in pulmonary tuberculosis.

PMID- 15429163
TI  - Lungpleura graft for esophagoesophageal anastomosis; an experimental study.

PMID- 15429164
TI  - Tumors of the adrenal gland.

PMID- 15429165
TI  - Diagnosis of hydatid cyst of the kidney.

PMID- 15429166
TI  - Renal adenoma: survey of reported clinical cases and another case report.

PMID- 15429167
TI  - Reflex renal suppression.

PMID- 15429168
TI  - Intubated ureterotomy: report of animal experimentation and clinical cases.

PMID- 15429169
TI  - Observations of isolated sigmoid loop substitution following total cystectomy in
      the dog: preliminary report.

PMID- 15429170
TI  - Vesicovaginal fistula of tuberculous origin.

PMID- 15429171
TI  - Prostatism in the Negro with clinical and pathological studies.

PMID- 15429172
TI  - Common causes for unsatisfactory results in endoscopic prostatic resection.

PMID- 15429173
TI  - Conservative operations for carcinoma of the prostate: analysis of 109 cases.

PMID- 15429174
TI  - Urinary complications of anorectal suppuration.

PMID- 15429175
TI  - Diphallus (double penis).

PMID- 15429176
TI  - Determination of the bacterial content of the urethra: a new method, with results
      of a study of 82 men.

PMID- 15429177
TI  - The susceptibility of pleuropneumonia-like organisms to the in vitro action of
      antibiotics: aureomycin, chloramphenicol, dihydrostreptomycin, streptomycin, and
      sodium penicillin G.

PMID- 15429178
TI  - Surgery for the conservation of renal parenchyma.

PMID- 15429179
TI  - Implantation of renal parenchymal carcinoma.

PMID- 15429180
TI  - Differential diagnosis between renal tumor and renal cyst.

PMID- 15429181
TI  - Indications for conservative surgery in certain renal tumors: a study based on
      the growth pattern of the cell carcinoma.

PMID- 15429182
TI  - Leukoplakia of the renal pelvis.

PMID- 15429183
TI  - Diagnostic and therapeutic considerations in renal aneurysm with a report of two
      additional cases.

PMID- 15429184
TI  - Supernumerary kidney: a summary of 51 reported cases.

PMID- 15429185
TI  - Congenital solitary kidney with crossed ureter.

PMID- 15429186
TI  - Hypertension associated with unilateral renal disease: report of 2 cases.

PMID- 15429187
TI  - The use of streptomycin in the treatment of renal tuberculosis.

PMID- 15429188
TI  - Segmental renal function studies.

PMID- 15429189
TI  - Intestinal and gastric perfusion in a patient with severe chronic uremia.

PMID- 15429190
TI  - A consideration of the ureteral stump subsequent to nephrectomy.

PMID- 15429191
TI  - Injuries of the ureters following pelvic surgery.

PMID- 15429192
TI  - The use of a suspension of caroid for maintaining the patency of indwelling
      ureteral catheters.

PMID- 15429193
TI  - Management of upper urinary tract calculus.

PMID- 15429194
TI  - Primary carcinoma of the ureter: report of a case living over twenty-five years
      following nephro-ureterectomy.

PMID- 15429195
TI  - Ureterointestinal anastomosis and cystectomy.

PMID- 15429197
TI  - Cystectomy for carcinoma of the bladder.

PMID- 15429196
TI  - Mesenchymoma, secondary invasion of the urinary bladder: case report.

PMID- 15429198
TI  - Rapid freezing of the bladder: an experimental and clinical study.

PMID- 15429199
TI  - Intravesical rupture of bladder during transurethral prostatic resection.

PMID- 15429200
TI  - Analysis of reappearance of dysuric symptoms following prostatic surgery.

PMID- 15429201
TI  - Retropubic surgery.

PMID- 15429202
TI  - Prostatectomy, a comparison of the results of the retropubic and suprapubic
      approach.

PMID- 15429203
TI  - An evaluation of the retropubic prostatic operation.

PMID- 15429204
TI  - Leiomyoma of the prostate: case report.

PMID- 15429205
TI  - Bilateral carcinoma of the male breasts associated with prolonged stilbestrol
      therapy for carcinoma of the prostate.

PMID- 15429206
TI  - The Denis Browne operation for hypospadias.

PMID- 15429207
TI  - Production of epithelial lined tubes from buried strips of intact skin.

PMID- 15429208
TI  - Angiomatous malformations of the glans penis.

PMID- 15429209
TI  - Use of dicumarol in persistent priapism.

PMID- 15429210
TI  - Calculus formation in the epididymis.

PMID- 15429211
TI  - The use of urecholine in the management of chronic urinary retention.

PMID- 15429212
TI  - Reiter's syndrome treated successfully with dihydrostreptomycin.

PMID- 15429213
TI  - Improved pediatric excretory urography.

PMID- 15429214
TI  - Cardiac studies in the urologic patient.

PMID- 15429215
TI  - Multiple tumors of the urinary tract.

PMID- 15429216
TI  - A proposal for joint action against congenital syphilis.

PMID- 15429217
TI  - Status of treatment of syphilitic pregnant women and of children who have
      congenital syphilis.

PMID- 15429218
TI  - How to evaluate positive Kahn tests in infants.

PMID- 15429219
TI  - The dentist's role in finding congenital syphilis.

PMID- 15429220
TI  - EIGHT point agreement of 1948.

PMID- 15429221
TI  - Effectiveness of penicillin in preventing congenital syphilis when administered
      prior to pregnancy.

PMID- 15429222
TI  - The patient's attitude toward venereal disease education.

PMID- 15429223
TI  - The identity of Neisseria other than the gonococcus isolated from the genito
      urinary tract.

PMID- 15429224
TI  - [Ligature of the left gastric artery in connection with operative immobilization
      of the stomach].

PMID- 15429225
TI  - [Distribution of the mass of esophageal nerves].

PMID- 15429226
TI  - [Secretory and morphologic modification in the stomach following vagotomy and
      partial denervation].

PMID- 15429227
TI  - [Method of pseudo-meals for the determination of radical effects of vagotomy in
      surgical clinic].

PMID- 15429228
TI  - [Case of resection of the stomach one year after vagotomy].

PMID- 15429229
TI  - [Microscopy of the margins of perforating peptic ulcers].

PMID- 15429230
TI  - [150 cases of perforating peptic ulcer and remote results of its therapy].

PMID- 15429231
TI  - [Acute dilation of the stomach].

PMID- 15429232
TI  - [A new hermetic method of resection and anastomoses of the gastrointestinal
      tract].

PMID- 15429233
TI  - [Method of resection of the stomach in perforating peptic ulcer].

PMID- 15429234
TI  - [Multiple ulcers of the cardia].

PMID- 15429235
TI  - [A case of perforating peptic ulcer caused by intestinal obstruction].

PMID- 15429236
TI  - [A case of intestinal obstruction following resection of the stomach].

PMID- 15429237
TI  - [Erroneous application of gastrointestinal anastomoses].

PMID- 15429239
TI  - [Huge postoperative hernias and their surgical therapy].

PMID- 15429238
TI  - [A case of benign esophageal tumor complicated by diverticulum].

PMID- 15429240
TI  - [Technic of marine and surgical knots].

PMID- 15429241
TI  - [Method of determination of sensitivity of microorganisms to antibiotics].

PMID- 15429242
TI  - [Pathogenesis of cardiac neuroses].

PMID- 15429243
TI  - [Diagnosis of latent surgical infection].

PMID- 15429244
TI  - [Blood transfusion and administration of medicinal solutions through the bone
      marrow].

PMID- 15429245
TI  - [Functional phlebotonometry].

PMID- 15429246
TI  - [Diagnosis of early, stages of hypertension].

PMID- 15429247
TI  - [Clinical effect and pathophysiologic modifications in surgical therapy of
      hypertension].

PMID- 15429248
TI  - [Correlation of hypertension and nephropathy in pregnancy].

PMID- 15429249
TI  - [Blood circulation rate in separate parts of the hemopoietic system].

PMID- 15429250
TI  - [Dynamics of vascular rate in heart diseases].

PMID- 15429251
TI  - [Hypotonic syndrome of different origin and psychic modification].

PMID- 15429252
TI  - [Regulation of carbohydrate metabolism in hypotonia].

PMID- 15429253
TI  - [Effect of determined muscular work on the modification of carbon anhydrase as a
      method of functional diagnosis in disorders of the respiratory and hemopoietic
      systems].

PMID- 15429254
TI  - [Case of isolated volvulus of the stomach].

PMID- 15429255
TI  - [A method for the determination of maximal arterial pressure].

PMID- 15429256
TI  - [Hemopoietic modifications in peptic ulcer before and following surgery].

PMID- 15429257
TI  - [Dynamics of reticulo-endothelial block, oligocythemia and hydremia in malaria].

PMID- 15429258
TI  - [Erroneous diagnosis of infarct of the myocardium].

PMID- 15429259
TI  - [Blood coagulation in burns].

PMID- 15429260
TI  - [German experience with the frog test for pregnancy].

PMID- 15429261
TI  - [Determination of PAS in blood: a new pattern].

PMID- 15429262
TI  - [Cytology of the cerebrospinal fluid after injection of various substances. III.
      Anesthetics].

PMID- 15429263
TI  - Medical education.

PMID- 15429264
TI  - Memories of post graduate teaching.

PMID- 15429265
TI  - Poliomyelitis-tonsillectomy survey--year 1949.

PMID- 15429266
TI  - Further observations of the effects of thyroid insufficiency on the nasal mucosa.

PMID- 15429267
TI  - The treatment of surgical shock.

PMID- 15429268
TI  - Allergy; effective treatments used in otolaryngology.

PMID- 15429269
TI  - Determining factors in composing and analyzing speech-hearing tests.

PMID- 15429270
TI  - The recruitment of loudness phenomenon.

PMID- 15429271
TI  - Radiation therapy of cancer of the larynx.

PMID- 15429272
TI  - HEARING aids accepted by the Council on Physical Medicine of the American Medical
      Association.

PMID- 15429273
TI  - [General view of pathological anatomy of the fetus and of the newborn].

PMID- 15429274
TI  - [Cases of infantile visceral leishmaniasis observed in the ten-year period 1939
      49 in the Province of Brindisi].

PMID- 15429275
TI  - [The best dose for children in massive vitamin D2 therapy].

PMID- 15429276
TI  - [The use of protein hydrolysates in the therapy of the premature].

PMID- 15429277
TI  - [Bronchoscopy and collapsotherapy].

PMID- 15429278
TI  - [Bronchoscopy and broncho-pulmonary suppurations].

PMID- 15429279
TI  - [Two cases of hematemesis].

PMID- 15429280
TI  - [A new synthetic curare].

PMID- 15429281
TI  - [Artificial feeding of the normal infant from birth to 2 years].

PMID- 15429282
TI  - [Out of the mouths of babes....].

PMID- 15429283
TI  - [Tendon sutures].

PMID- 15429284
TI  - [Treatment of prolapse of the genitals following hysterectomy].

PMID- 15429285
TI  - [Lateral fistulas of the neck].

PMID- 15429286
TI  - [The use of narcogen in urology].

PMID- 15429287
TI  - [Dislocation of Lisfranc's joint].

PMID- 15429288
TI  - [Venous pressure and circulation time in cor pulmonale].

PMID- 15429289
TI  - [Radiation treatment of goiters].

PMID- 15429290
TI  - [Treatment of narcomania by conditioned vomitive reaction].

PMID- 15429292
TI  - [Bacteriology; review].

PMID- 15429291
TI  - [Medical services in schools in Brno].

PMID- 15429293
TI  - [The problem of dosage in the treatment of endocrine disorders].

PMID- 15429294
TI  - [Importance of recognition of coli bacteria].

PMID- 15429295
TI  - [Phosphatases in blood serum and its clinical significance].

PMID- 15429296
TI  - [Porphyria].

PMID- 15429297
TI  - [Recurrent bilateral paralysis].

PMID- 15429298
TI  - [Refrigeration anesthesia].

PMID- 15429299
TI  - [Treatment of chronic pemphigus with hormones].

PMID- 15429300
TI  - [Two cases of placenta accreta with congenital malaria].

PMID- 15429301
TI  - [Medical incunabula in metropolitan library in Zagreb].

PMID- 15429302
TI  - [Surgical treatment of congenital dislocation of the hip in children].

PMID- 15429303
TI  - [Mega-oesophagus treated by Heller's operation; presentation of radiograms].

PMID- 15429304
TI  - [Case of Klippel-Feil syndrome].

PMID- 15429305
TI  - [Laryngeal cancers of slow evolution].

PMID- 15429306
TI  - [Case of stenosing tumor of the thoracic esophagus treated by radiotherapy with 5
      year clinical cure].

PMID- 15429307
TI  - [Two cases of orbital cellulitis].

PMID- 15429308
TI  - [Cicatricial stenosis of the rhino-pharynx].

PMID- 15429309
TI  - [Treatment of hematomas and abscesses of the nasal septum by antibiotics and new
      hemostatics].

PMID- 15429310
TI  - [Voluminous lipoma of the transverse colon; segmentary colectomy].

PMID- 15429311
TI  - [Foreign bodies in the abdomen of a toxicomaniac].

PMID- 15429312
TI  - [Voluminous solitary osteochondroma of the articulation of the knee].

PMID- 15429313
TI  - [Sub-adventitial rupture of the left external iliac artery].

PMID- 15429314
TI  - [Fracture of an osteoma of the Achilles tendon].

PMID- 15429315
TI  - [Tumors of the tunica vaginalis].

PMID- 15429316
TI  - [Primary diaphyseal resection for acute osteomyelitis].

PMID- 15429317
TI  - [Radiogram of perforation of a gastric ulcer].

PMID- 15429318
TI  - [Anthrax of the kidney fistulized into the perirenal area and into the renal
      sinus; penicillin therapy by endo-ureteral route; cure].

PMID- 15429319
TI  - [Surgical treatment of tibioperoneal diastasis; two cases].

PMID- 15429320
TI  - [Total incarceration of the small intestine in the retro-anastomotic crevice
      after gastrectomy; absence of acute accidents].

PMID- 15429321
TI  - [Two arteriograms for tumors].

PMID- 15429323
TI  - A code for the healing profession?

PMID- 15429322
TI  - [Case of seminoma of the ovary in a 12-year-old girl].

PMID- 15429324
TI  - The principle of subsidiary.

PMID- 15429325
TI  - Chorea gravidarum; case report.

PMID- 15429326
TI  - [Surgery for jaundice due to hepatitis; peri-arterial hepatic sympathectomy].

PMID- 15429327
TI  - [Treatment of the pain following zoster].

PMID- 15429328
TI  - [Left hemiplegia following a contusion of the internal carotid in a child;
      treatment by five stellate infiltrations; almost complete cure].

PMID- 15429329
TI  - [Papillary tumors of the thyroid body].

PMID- 15429330
TI  - [Cervical rib syndrome].

PMID- 15429331
TI  - [Spinal arthrodesis using the Wilson technic].

PMID- 15429332
TI  - [Surgical treatment of interauricular communication; experimental work].

PMID- 15429333
TI  - [Some cases of surgery for pulmonary tuberculosis with doubtful indications].

PMID- 15429334
TI  - [The Gougerot-Sjogren syndrome].

PMID- 15429335
TI  - [Case of divergent carpometacarpal dislocation; dorsal dislocation of the middle
      metacarpals and palmar dislocation of the fifth metacarpal].

PMID- 15429336
TI  - [Preoperative correction of serious scoliosis].

PMID- 15429337
TI  - [Three observations of choledochoduodenostomy after choledochotomy for lithiasis
      of the common bile duct].

PMID- 15429338
TI  - [Indications for venous ligations in the treatment of disorders of the peripheral
      arteries].

PMID- 15429339
TI  - [Case of fracture of the scaphoid consolidated by late immobilization].

PMID- 15429340
TI  - [Colorectoplasty].

PMID- 15429341
TI  - [Voluminous osteoma of ethmoidal origin occupying the anterior portion of the
      base of the cranium].

PMID- 15429342
TI  - [Biliary surgery under manometric and radiographic per-operative control].

PMID- 15429343
TI  - [Ileal and colic sequels of radiotherapy for cancer of the cervix uteri].

PMID- 15429344
TI  - Modern anthelmintics for farm animals and poultry.

PMID- 15429345
TI  - CHEMICAL and medical studies in the colonies.

PMID- 15429346
TI  - A new manufacturing laboratory in Johannesburg.

PMID- 15429348
TI  - AUSTRALIAN research on fungicides for textiles and other materials.

PMID- 15429347
TI  - A chromatographic repetition plant.

PMID- 15429349
TI  - RADIOCHEMISTRY at Harwell; impressions of a visit to the atomic energy research
      establishment.

PMID- 15429350
TI  - PHOTOGRAPHIC sensitisers.

PMID- 15429351
TI  - COSMETICS and toilet preparations.

PMID- 15429353
TI  - CHEMOTHERAPY.

PMID- 15429352
TI  - FERTILISERS and plant nutrients.

PMID- 15429354
TI  - PLANT and equipment.

PMID- 15429355
TI  - CURRENT research on cosmetics.

PMID- 15429356
TI  - [Malignant secondary endocarditis].

PMID- 15429357
TI  - [Pedo-psychiatric study of a group of children of tuberculous parents].

PMID- 15429358
TI  - [Paris public welfare appropriations].

PMID- 15429360
TI  - [Public health in Rumania].

PMID- 15429359
TI  - [Unpunished war crimes].

PMID- 15429361
TI  - [Visual function in work].

PMID- 15429362
TI  - [Research in Belgian pyrite mines on the risks of lead poisoning].

PMID- 15429363
TI  - [Social security and industrial medicine; a propos of an article by Dr. R.
      Bender].

PMID- 15429364
TI  - [Industrial medicine and small business].

PMID- 15429365
TI  - [Anti-dust masks].

PMID- 15429366
TI  - [Filtrating dust masks with self-cleansers].

PMID- 15429367
TI  - [Dermatology, venereology, syphilography in 1949].

PMID- 15429368
TI  - [Vitiligo].

PMID- 15429369
TI  - [The real value of tests in eczema].

PMID- 15429370
TI  - [Review of physiology].

PMID- 15429371
TI  - [New experimental methods permitting estimation of the strength of cardiotonics
      in mammals].

PMID- 15429372
TI  - [Adrenochrome and its therapeutic possibilities].

PMID- 15429373
TI  - [Combined antibiotics in the treatment of pulmonary tuberculosis].

PMID- 15429374
TI  - [Present medico-social aspect of pulmonary tuberculosis; necessity for pre
      sanatorium treatment in specialized urban centers].

PMID- 15429375
TI  - [Preventorium and sanatorium treatment of primary tuberculosis of young
      children].

PMID- 15429376
TI  - [Works concerning cardiovascular pathology which appeared in France during 1949].

PMID- 15429377
TI  - [Recurrent Osler's disease].

PMID- 15429378
TI  - [Erythrocyte sedimentation in cardiovascular pathology].

PMID- 15429379
TI  - [Anatomy of the cervical spine from the point of view of its movements].

PMID- 15429380
TI  - [Radiology of the cervical spine and indications for radiotherapy].

PMID- 15429381
TI  - [Headache of cervical origin].

PMID- 15429382
TI  - [Differential diagnosis of pain in the upper extremities].

PMID- 15429383
TI  - [Physiotherapeutic treatment of rheumatism of the cervical spine and
      cervicobrachial pain].

PMID- 15429384
TI  - [Treatment of cervical and cervicobrachial pains by manipulations].

PMID- 15429385
TI  - [Pharmacy and social security in France].

PMID- 15429386
TI  - [Polarography; a new method of determination and investigation, at the service of
      biology and medicine].

PMID- 15429387
TI  - [The Chicago Conference on ACTH].

PMID- 15429388
TI  - [Cancer in the young].

PMID- 15429389
TI  - [Doctor Leon Weber-Bauler was 80 years old on June 12, 1950].

PMID- 15429390
TI  - [Clinical and therapeutic study of cervical rheumatism].

PMID- 15429391
TI  - [Dietetic cooking is a chapter of gastrotechnic].

PMID- 15429392
TI  - [Fruit juices in the diet of healthy and sick persons].

PMID- 15429393
TI  - [Notes on practical dietetics; causes of error in the use of tables of food
      composition].

PMID- 15429394
TI  - [Control of insects of house and man].

PMID- 15429395
TI  - [Genital localizations of Bancroft's filariasis in French West Africa].

PMID- 15429396
TI  - [Practical superiority of diamino-diphenyl-sulfone (1358 F) over complex
      disubstituted sulfones in the treatment of leprosy].

PMID- 15429397
TI  - [Titrimetric assay of solutions of DDT in petroleum; percentage in total DDT and
      in the active isomer pp'].

PMID- 15429398
TI  - [Anatomo-clinical study of a case of hemato-chyluria].

PMID- 15429399
TI  - [Clinically and bacteriologically atypical form of plague].

PMID- 15429400
TI  - [Exchange transfusion and peritoneal dialysis; their possible practical use in
      the colonies].

PMID- 15429401
TI  - [Glycemia and glycorrhachia compared in the healthy Negro and in the Negro with
      trypanosomiasis].

PMID- 15429402
TI  - [Bismuth therapy of syphilis].

PMID- 15429403
TI  - [Conessine bromohydrate].

PMID- 15429404
TI  - [Toxicity of dichloro-diphenyltrichloroethane].

PMID- 15429406
TI  - Trends in the practice of medicine.

PMID- 15429405
TI  - [Trypanosomiasis].

PMID- 15429407
TI  - Exfoliative cytology as a tool for the clinician.

PMID- 15429408
TI  - Chronic arthritis in Reiter's syndrome; report of two cases.

PMID- 15429409
TI  - Surgical treatment of ulcerative colitis.

PMID- 15429410
TI  - Avulsion fracture of the tibial spine; report of a case with improved surgical
      treatment.

PMID- 15429411
TI  - The doctor as a politician.

PMID- 15429412
TI  - CARE of hand injuries; open fractures.

PMID- 15429413
TI  - Arthur Carlisle Christie, M. D., F.A.C.P., President of Medical Society of
      District of Columbia.

PMID- 15429414
TI  - The problems of the general practitioner.

PMID- 15429415
TI  - Psychiatry, psychosomatic medicine and the general practitioner.

PMID- 15429416
TI  - The differentiation of psychosis from psychoneurosis.

PMID- 15429417
TI  - Doctors: drugs: patients.

PMID- 15429418
TI  - Psychosomatic aspects of pain.

PMID- 15429419
TI  - The psychosomatic aspects of gynecology.

PMID- 15429420
TI  - Correlation of the dermatologic and psychiatric approaches to the treatment of
      neurodermatitis.

PMID- 15429421
TI  - The holistic treatment of neurologic disease.

PMID- 15429422
TI  - Psychiatric aspects of treatment for intractable pain in the phantom limb.

PMID- 15429423
TI  - Indications for and complications of prefrontal lobotomy.

PMID- 15429424
TI  - The tyranny of certain terms.

PMID- 15429425
TI  - Psychologic testing from the standpoint of the general practitioner.

PMID- 15429426
TI  - Some common diagnostic problems in children.

PMID- 15429427
TI  - The practitioner and the older age groups; psychosomatic aspects.

PMID- 15429428
TI  - Classification and general aspects of amyloidosis.

PMID- 15429429
TI  - Primary systemic amyloidosis with symptoms and signs of liver disease; diagnosis
      by liver biopsy; report of case.

PMID- 15429430
TI  - Primary systemic amyloidosis; report of 2 cases.

PMID- 15429431
TI  - Amyloid disease of the heart.

PMID- 15429432
TI  - Amyloid tumors of the larynx and trachea.

PMID- 15429433
TI  - Amyloidosis complicating myeloma.

PMID- 15429434
TI  - Hepatic manifestations in secondary amyloidosis.

PMID- 15429435
TI  - Laboratory and biopsy diagnosis of amyloidosis.

PMID- 15429436
TI  - Coarctation of the aorta with hypotension in the left arm; physiologic
      observations on direct intra-arterial pressures and flow of blood.

PMID- 15429437
TI  - Pulmonary stenosis without septal defect associated with recurrent ascites;
      report of a case.

PMID- 15429438
TI  - The treatment of pernicious anemia and other macrocytic anemias with vitamin B12.

PMID- 15429439
TI  - Ethyl carbamate (urethane) in the treatment of chronic myelocytic leukemia;
      results of a three-year study.

PMID- 15429440
TI  - Splenectomy in women of the childbearing age; its possible effect on fertility
      and the course of any subsequent pregnancies.

PMID- 15429441
TI  - The real issues in prepay medicine.

PMID- 15429442
TI  - Health for the forty-plus.

PMID- 15429443
TI  - STORY of a DP doctor.

PMID- 15429445
TI  - FOR dents in the derriere.

PMID- 15429444
TI  - HOME for 2, office for 3.

PMID- 15429446
TI  - USE pictures when you talk.

PMID- 15429447
TI  - DOCTORS' wives pitch in.

PMID- 15429448
TI  - She helps doctors set fair fees.

PMID- 15429450
TI  - YOU'VE got to give them credit.

PMID- 15429449
TI  - What counts as medical evidence.

PMID- 15429451
TI  - NEW yardstick of stock values.

PMID- 15429453
TI  - GET acquainted with your bank.

PMID- 15429452
TI  - WHAT auto clubs offer the doctor.

PMID- 15429454
TI  - How I index my medical reading.

PMID- 15429455
TI  - VISIT to a $50,000-a-year cultist.

PMID- 15429456
TI  - ARE x-ray fees too high?

PMID- 15429458
TI  - LAKESIDE office and residence.

PMID- 15429457
TI  - AMA elects new leaders, new projects.

PMID- 15429459
TI  - M.D.--the U.S. doctor.

PMID- 15429460
TI  - The boys in room 1106; an inside report on how the Democratic National Committee
      switched its health platform.

PMID- 15429461
TI  - U.S. physicians, what they do, how they've increased.

PMID- 15429463
TI  - How to safeguard your belongings.

PMID- 15429462
TI  - PLIGHT, of Britain's hospitals.

PMID- 15429464
TI  - They give till it hurts.

PMID- 15429465
TI  - QUIZ on socialized medicine.

PMID- 15429466
TI  - DOCTORS hammer out defense plans.

PMID- 15429467
TI  - Labor looks at prepaid medicine.

PMID- 15429468
TI  - YOU can now rent X-ray equipment.

PMID- 15429469
TI  - POLITICOS pressed for health views.

PMID- 15429470
TI  - RECORD ad campaign takes shape.

PMID- 15429471
TI  - The prevention of deformity in rheumatic disease.

PMID- 15429472
TI  - The tragedy of stammering and its relation to reeducation.

PMID- 15429473
TI  - Hepatomegaly in the natives of northern Australia.

PMID- 15429474
TI  - "Myanesin" as a relaxing agent in anaesthesia.

PMID- 15429475
TI  - Foreign bodies in the food passages of children.

PMID- 15429476
TI  - Bite by funnel web spider.

PMID- 15429478
TI  - A new concept of the nature of the preeclamptic syndrome of pregnancy.

PMID- 15429477
TI  - Sudden death due to a combination of cardiac anomalies.

PMID- 15429479
TI  - A photoelectric method for the determination of red cell numbers and haemoglobin
      in peripheral blood.

PMID- 15429480
TI  - The use of the male toad, Bufo marinus, for pregnancy tests.

PMID- 15429481
TI  - Multiple myelomatosis, with reports on three cases.

PMID- 15429482
TI  - President's address, Australasian Medical Congress.

PMID- 15429483
TI  - AUSTRALASIAN Medical Congress (British Medical Association), Brisbane, May-June,
      1950.

PMID- 15429484
TI  - AUSTRALASIAN Medical Congress (British Medical Association), Brisbane, May-June,
      1950.

PMID- 15429485
TI  - AUSTRALASIAN Medical Congress (British Medical Association) Brisbane, May-June,
      1950.

PMID- 15429486
TI  - An address.

PMID- 15429487
TI  - Clinical aspects of poliomyelitis during the epidemic of 1949.

PMID- 15429488
TI  - Recent developments in the epidemiology of poliomyelitis, with special reference
      to the epidemic of 1949.

PMID- 15429489
TI  - Poliomyelitis--hospital management.

PMID- 15429490
TI  - The after-care of poliomyelitis.

PMID- 15429491
TI  - The egregious Dr. Beaney of the Beaney Scholarships.

PMID- 15429492
TI  - Vitamin B deficiency in general practice.

PMID- 15429493
TI  - Mortality in Australia: population and mortality data.

PMID- 15429494
TI  - A regional plan of hospital development.

PMID- 15429495
TI  - Further experiences with the inversion operation for indirect inguinal hernia.

PMID- 15429496
TI  - A medical account of a voyage on a convict vessel.

PMID- 15429497
TI  - Some aspects of healing.

PMID- 15429498
TI  - A report on two cases of sulphonamide anuria and suggested treatment.

PMID- 15429499
TI  - Medical history--do we use it wisely?

PMID- 15429500
TI  - Tuberculosis mortality in Australia, 1908 to 1945.

PMID- 15429501
TI  - Salt depletion and mercury poisoning: potential dangers in the treatment of the
      failing heart.

PMID- 15429502
TI  - A case of thoracopagus tribrachius dipus.

PMID- 15429503
TI  - A case of syncephalic twins.

PMID- 15429504
TI  - Observations on recent discoveries connected with the blood groups Rh (Cw and
      Du), M-N (S), Lewis (Le), together with the Rh and M-N types and agglutinogen P
      in white Australians.

PMID- 15429505
TI  - Combined methyl thiouracil and propyl thiouracil in the treatment of
      thyreotoxicosis.

PMID- 15429507
TI  - Acroparaesthesia.

PMID- 15429506
TI  - A histological evaluation of appendicectomy.

PMID- 15429508
TI  - The use of the Harris tube for intestinal intubation.

PMID- 15429509
TI  - Report of a case of pellagra.

PMID- 15429510
TI  - Some comparisons of hospital pathology, morbidity and mortality in 1910 and in
      1948.

PMID- 15429511
TI  - Should the nutritive value of Australian bread be improved by raising the
      extraction rate of flour?

PMID- 15429512
TI  - A parasitological survey of five New Guinea villages.

PMID- 15429513
TI  - Report on four cases of typhoid fever treated with chloromycetin.

PMID- 15429514
TI  - Two unusual foreign bodies.

PMID- 15429515
TI  - Chronic penetrating gastric ulcer with pernicious anaemia.

PMID- 15429516
TI  - The treatment of varicose and allied gravitational eczema and ulceration with
      tetra ethyl ammonium bromide.

PMID- 15429517
TI  - The malaria problem in Australia and the Australian Pacific territories.

PMID- 15429518
TI  - Tuberculosis mortality of childhood in Australia.

PMID- 15429519
TI  - The use of "sodium pentothal" administered continuously in abdominal surgery.

PMID- 15429520
TI  - Double uterus with complete vaginal septum.

PMID- 15429521
TI  - Agranulocytopenia following chloromycetin: report on two cases.

PMID- 15429522
TI  - The place of the pathologist in modern medicine.

PMID- 15429523
TI  - Facial paralysis due to fracture of the base of the skull: surgical therapy.

PMID- 15429524
TI  - Tidal drainage: an efficient apparatus.

PMID- 15429525
TI  - Dr. George Owen Willis, a pioneer Queensland surgeon.

PMID- 15429526
TI  - Control of malnutrition.

PMID- 15429527
TI  - The saliva: a short review, with special reference to dental caries.

PMID- 15429529
TI  - The influence of maternal measles (morbilli) on the unborn child.

PMID- 15429528
TI  - The clinical significance of sodium and potassium analyses of biological fluids:
      their estimation by flame spectrophotometry.

PMID- 15429530
TI  - The estimation of pregnanediol in urine.

PMID- 15429531
TI  - Modern treatment of psoriasis.

PMID- 15429532
TI  - Some aspects of food allergy: effects of "bleached" (agenised) flour; preliminary
      report.

PMID- 15429533
TI  - The diagnosis and treatment of lung abscess.

PMID- 15429534
TI  - Modern methods of induction of labour.

PMID- 15429535
TI  - The common sense of modern psychodynamics for general practitioners and others.

PMID- 15429536
TI  - Modern trends in ophthalmology.

PMID- 15429537
TI  - Treatment of corneal ulcers.

PMID- 15429538
TI  - The value of corneal grafts for ophthalmic lesions.

PMID- 15429539
TI  - The diagnosis and treatment of cataract in children.

PMID- 15429540
TI  - Detachment of the retina.

PMID- 15429541
TI  - The provision of contact lenses in a state medical service.

PMID- 15429542
TI  - Squint in children.

PMID- 15429543
TI  - Dental caries.

PMID- 15429544
TI  - Unerupted teeth.

PMID- 15429545
TI  - Periodontia.

PMID- 15429546
TI  - The dental aspects of the treatment of clefts and perforations of the palate.

PMID- 15429547
TI  - The deciduous dentition.

PMID- 15429548
TI  - Some aspects of fractures of the maxillae.

PMID- 15429549
TI  - Modern trends in orthodontic treatment in children.

PMID- 15429550
TI  - The role of the physiotherapist.

PMID- 15429551
TI  - The radiology of lesions of the alimentary tract in general practice.

PMID- 15429552
TI  - Mucous polypi of the nose.

PMID- 15429553
TI  - The management of the diabetic child.

PMID- 15429554
TI  - Modern treatment of the anaemias.

PMID- 15429555
TI  - Osteochondromatosis: a choristomatosis of articular synovial membranes.

PMID- 15429556
TI  - The diagnosis and treatment of cardiac pain.

PMID- 15429557
TI  - The modern treatment of genital prolapse.

PMID- 15429558
TI  - Surgery in hypertension.

PMID- 15429559
TI  - The diagnosis and treatment of cardiac pain.

PMID- 15429560
TI  - The modern treatment of Volkmann's ischaemia.

PMID- 15429561
TI  - Miscarriages.

PMID- 15429562
TI  - A palliative treatment for inoperable cancer.

PMID- 15429563
TI  - The incidence and control of acute rheumatism in childhood.

PMID- 15429564
TI  - Ruptured ectopic pregnancy complicated by intestinal obstruction.

PMID- 15429565
TI  - Daily variations in basal metabolic recordings throughout the entire menstrual
      cycle determined at home under ideal circumstances.

PMID- 15429566
TI  - CARDIAC arrhythmias.

PMID- 15429567
TI  - WILLIAM Freeman Snow.

PMID- 15429568
TI  - Current urological topics.

PMID- 15429569
TI  - Oxygen therapy.

PMID- 15429570
TI  - Mental research yesteryear and today.

PMID- 15429571
TI  - Ankle sprain or ligamentous fracture of the ankle.

PMID- 15429572
TI  - Observations on thyroid disease.

PMID- 15429573
TI  - NEWER antibiotics having wide antibacterial spectra.

PMID- 15429574
TI  - Learn the indirect method for endolaryngeal operations.

PMID- 15429575
TI  - The emotional factor in disease.

PMID- 15429576
TI  - The importance of early diagnosis in psychiatric disorders.

PMID- 15429578
TI  - GONZALES Abreu y Herrera B. M.

PMID- 15429577
TI  - Functional thyroid disturbances in children.

PMID- 15429579
TI  - The evolution of a psychiatric program in Mississippi.

PMID- 15429580
TI  - International and Fourth American Congress on Gynecology and Obstetrics.

PMID- 15429581
TI  - HISTORY of women in medicine; medical women of North Carolina.

PMID- 15429582
TI  - Carcinomatosis of peritoneum and left pleura; toxemia.

PMID- 15429583
TI  - The treatment of chronic rheumatism by the use of adrenalin cream.

PMID- 15429584
TI  - Rheumatism in children; prevention and diagnosis.

PMID- 15429585
TI  - The law of abortion.

PMID- 15429586
TI  - Francis Adams.

PMID- 15429587
TI  - The 'one shot' treatments of venereal diseases.

PMID- 15429588
TI  - Rheumatism in children; treatment and conclusions.

PMID- 15429589
TI  - Hernia in children.

PMID- 15429590
TI  - Instrumental aids in general practice; the pneumothorax apparatus.

PMID- 15429591
TI  - Andrew Vesalius.

PMID- 15429592
TI  - REPORT on the Thirty-First Annual General Meeting of the Medical Practitioners'
      Union.

PMID- 15429593
TI  - Some psychiatric problems in general practice; the common psychiatric disorders.

PMID- 15429594
TI  - Two gynaecological conditions.

PMID- 15429595
TI  - Andrew Vesalius.

PMID- 15429596
TI  - Some psychiatric problems in general practice; psychiatric disorders of
      childhood.

PMID- 15429597
TI  - Bronchiectasis; its clinical features and treatment.

PMID- 15429598
TI  - Some psychiatric problems in general practice; some unusual psychiatric problems
      and difficulties.

PMID- 15429599
TI  - The facial neuralgias.

PMID- 15429600
TI  - Instrumental aids in general practice; the sigmoidoscope.

PMID- 15429601
TI  - Some psychiatric problems in general practice: special forms of treatment;
      physical methods.

PMID- 15429602
TI  - The teaching of first aid.

PMID- 15429603
TI  - LIFE in the private wing of a London hospital today.

PMID- 15429604
TI  - [Diabetes insipidus and its treatment].

PMID- 15429605
TI  - [Pain in angina pectoris and infarct of the myocardium].

PMID- 15429606
TI  - [PAS and other chemotherapeutic products as therapeutic agents and their
      indications in pulmonary tuberculosis].

PMID- 15429607
TI  - [Clinical diagnosis of malignant neoplasms of the breast].

PMID- 15429608
TI  - [Clinical diagnosis and treatment of Schottmuller's endocarditis lenta].

PMID- 15429609
TI  - [Arthropathy of the knee during menopause].

PMID- 15429610
TI  - [Progressive chondritis of the rib cartilages following a subphrenic abscess;
      failure of bacteriostats in treatment; pathogenesis].

PMID- 15429611
TI  - [Case of acute benign lymphocytic meningitis].

PMID- 15429612
TI  - [Diagnostic significance of incipient glaucoma in rural practice].

PMID- 15429613
TI  - [On law and custom].

PMID- 15429614
TI  - [Basis for splenectomy in internal diseases].

PMID- 15429615
TI  - [Deductions obtained during 8 years of treating gastroduodenal ulcers with ul
      cladene].

PMID- 15429616
TI  - [Diagnosis of the transverse medullary syndrome].

PMID- 15429617
TI  - [Mathematics of solutions].

PMID- 15429618
TI  - [Indications for amputation and prevention of disability in recent grave
      traumatism of the fingers and hand].

PMID- 15429619
TI  - [Curious allergic acrodermatosis].

PMID- 15429620
TI  - [Peritonitis as a consequence of perforation of a healthy intestinal loop by
      Ascaris lumbricoides].

PMID- 15429621
TI  - [Some commentaries on the case of "Olmer's exanthematous fever treated with
      chloromycetin"].

PMID- 15429622
TI  - [Treatment of the common infectious syndrome].

PMID- 15429623
TI  - [Therapy with antibiotics].

PMID- 15429624
TI  - [Dr. Sorapan de Rieros; first proverbialist doctor].

PMID- 15429625
TI  - [Streptomycin in osteoarticular tuberculosis].

PMID- 15429626
TI  - [Etiology, symptomatology, localization and distribution of cancer of the
      larynx].

PMID- 15429627
TI  - [Professional guidance and mental hygiene].

PMID- 15429628
TI  - [Histamine therapy in the treatment of sciatica].

PMID- 15429629
TI  - [Pathological exodontia].

PMID- 15429630
TI  - [Osteolytic osteosarcoma of the proximal metaphysis of the tibia].

PMID- 15429631
TI  - [Bleeding polypus of the nasal septum].

PMID- 15429632
TI  - [Initial melitococcic cervical spondylitis].

PMID- 15429633
TI  - [Treatment of fractures by the rural doctor].

PMID- 15429634
TI  - [Vitamin B12].

PMID- 15429635
TI  - [Cholera epidemics of the 19th century in Alava].

PMID- 15429636
TI  - [Urinary excretion of corticosteroids in some endocrine and non-endocrine
      diseases].

PMID- 15429637
TI  - [Bacteriostatic action in vitro of p-aminosalicylic acid (PAS) on Mycobacterium
      tuberculosis].

PMID- 15429638
TI  - [Studies on renin in experimental traumatic shock. III.--Influence of renal
      denervation on the effect of experimental traumatic shock on the renin content in
      the cortex of the kidney and in the blood].

PMID- 15429639
TI  - [Incomplete auriculoventricular block associated with acute infection in a young
      hyperthyroid].

PMID- 15429640
TI  - [Modern aspects of estrogens].

PMID- 15429641
TI  - [Measurement of the aqueous compartments of the organism].

PMID- 15429642
TI  - [Endocrinology].

PMID- 15429643
TI  - [Radium and radiotherapy in dermatology].

PMID- 15429644
TI  - [Gastric function tests applied to the study of physiology of the dog].

PMID- 15429645
TI  - [Intestinal perforations; surgical technic].

PMID- 15429646
TI  - [Synergic action of p-amino-salicylic acid and streptomycin in antituberculosis
      bacteriostasis].

PMID- 15429647
TI  - [Chloromycetin in salmonellosis].

PMID- 15429648
TI  - [Radioactive isotopes and their therapeutic application].

PMID- 15429649
TI  - [Treatment of Vincent's angina with penicillin].

PMID- 15429650
TI  - [Rickettsiasis in Uruapan; preliminary report].

PMID- 15429651
TI  - [Historical sketch of angiocardiography in Mexico and in foreign countries].

PMID- 15429652
TI  - [First experiences with succinic acid in the treatment of bronchial asthma].

PMID- 15429653
TI  - [Information on the production of BCG vaccine in the Laboratories for the
      preparation of BCG vaccine and investigations of Mexico, D.F].

PMID- 15429654
TI  - [Diethylcarbamazine in the onchocerciasis zone of Oaxaca].

PMID- 15429655
TI  - [Varicocele].

PMID- 15429656
TI  - [Local antihistamines in contact dermatitis].

PMID- 15429657
TI  - [Virus encephalitis transmitted by arthropods].

PMID- 15429658
TI  - [Euthanasia].

PMID- 15429659
TI  - [Preoperative pneumoperitoneum in the treatment of large eventrations].

PMID- 15429660
TI  - [Sabio Mutis and medicine in Santa Fe during the viceroyalty].

PMID- 15429661
TI  - [Carcinoma of the duodenum].

PMID- 15429662
TI  - [Tuberculosis of the larynx].

PMID- 15429663
TI  - [Ischiofemoral arthrodesis of the Brittain type].

PMID- 15429664
TI  - [Scleroderma].

PMID- 15429666
TI  - [New technics in angiocardiography].

PMID- 15429665
TI  - [PAS in the treatment of tuberculosis].

PMID- 15429667
TI  - [Notes on the Second European Congress of Gastroenterology].

PMID- 15429668
TI  - [Rheumatoid arthritis].

PMID- 15429669
TI  - [Differential diagnosis of ascites].

PMID- 15429670
TI  - [Chloromycetin in typhoid fever].

PMID- 15429671
TI  - [Clinical aspects of cerebral tumors].

PMID- 15429672
TI  - [Hepatorenal insufficiency in surgical practice].

PMID- 15429673
TI  - [Werlhof's disease].

PMID- 15429674
TI  - [Rheumatic aortic insufficiency].

PMID- 15429675
TI  - [The poet Joao de Deus; a psychological study].

PMID- 15429677
TI  - [Pathogenesis of hypertension].

PMID- 15429676
TI  - [Evolution of concepts on hyperpiesia and hypertension].

PMID- 15429678
TI  - [Return to work of hospitalized workers].

PMID- 15429679
TI  - [Industrial medicine and social action in the Gualeguaychu Refrigeration Plant].

PMID- 15429680
TI  - [Industrial medicine in the United States Army].

PMID- 15429681
TI  - Barrier creams and their evaluation.

PMID- 15429682
TI  - [Organization of a division of social assistance of the industrial social
      service].

PMID- 15429683
TI  - [Anatomy of the paths of approach to the trigeminus].

PMID- 15429684
TI  - [Blood proteins in syphilis; proteins in primary and secondary syphilis].

PMID- 15429685
TI  - [Mesodiencephalon and mental disease].

PMID- 15429686
TI  - [Benign exudative pericarditis].

PMID- 15429687
TI  - [Cancer of the bladder treated by ureterointestinal anastomosis and total
      cystectomy].

PMID- 15429688
TI  - [Clinical, neuroendocrinological and psychosomatic observations of little
      significance].

PMID- 15429689
TI  - [Bilateral combined collapsotherapy: thoracoplasty and pneumothorax].

PMID- 15429690
TI  - [The problem of gastroduodenal ulcer].

PMID- 15429691
TI  - The diagnosis and treatment of early phthisis.

PMID- 15429692
TI  - Hodgkin's disease and the skin.

PMID- 15429693
TI  - Clinical features and treatment of trigeminal neuralgia.

PMID- 15429694
TI  - A concise survey of the history of nutrition.

PMID- 15429695
TI  - [Not Available].

PMID- 15429697
TI  - [Foreign body in the duodenum].

PMID- 15429696
TI  - [Thrombosis of the humeral artery following an erect open dislocation;
      arteriectomy, cure].

PMID- 15429698
TI  - [Cure of an enormous eventration by preoperative pneumoperitoneum and by skin
      graft].

PMID- 15429699
TI  - [Extra-mucosal cardio-esophagotomy enlarged by intrathoracic route and associated
      with resection of the left dorsal splanchnic and sympathetic nerves in the
      treatment of megaesophagus, 6 personal cases].

PMID- 15429700
TI  - [Cerebral metastases of an operated breast cancer].

PMID- 15429701
TI  - [Non-surgical treatment of a perforated ulcer].

PMID- 15429702
TI  - [Cerebral metastases and breast cancer].

PMID- 15429704
TI  - [Familial case of androgynoid hermaphroditism].

PMID- 15429703
TI  - [Atlanto-odontoid disjunction; its mechanism seen by tomography in three cases of
      sub-occipital Pott's disease].

PMID- 15429705
TI  - [Observations drawn from the study of the respiration tracing registered under
      different forms of anesthesia].

PMID- 15429706
TI  - [Recto-sigmoidal cancer with invasion of the base of the bladder; Babcock's
      operation with partial cystectomy; continuous aspiration by the perineum in the
      combined operations by upper and lower routes].

PMID- 15429707
TI  - [Intestinal localizations of malignant lymphogranulomatosis].

PMID- 15429709
TI  - [Foreign body in the duodenum].

PMID- 15429708
TI  - [New case of regular androgynous hermaphroditism].

PMID- 15429710
TI  - [Chronic invagination of Meckel's diverticulum].

PMID- 15429711
TI  - [Intestinal invagination; apparent disinvagination upon barium enema; persistent
      invagination on the small intestine at operation; death].

PMID- 15429712
TI  - [Diffuse peritonitis following an extensive abscess of the liver].

PMID- 15429713
TI  - [Resection of the knee by the Charnley method].

PMID- 15429714
TI  - [Homogenous preserved bone grafts].

PMID- 15429715
TI  - [Intraperitoneal rupture of a liver abscess].

PMID- 15429716
TI  - [Peri-colic, peri-rectal and peri-sigmoidal pelvic strictures].

PMID- 15429717
TI  - [Case of peri-colic (peri-rectal) pelvic stricture].

PMID- 15429718
TI  - [Peri-colic pelvic stricture of adnexal origin simulating cancer].

PMID- 15429719
TI  - [Typical case of peri-coli pelvic stricture simulating cancer of the rectum].

PMID- 15429720
TI  - [Peri-colic pelvic stricture of adnexal origin].

PMID- 15429721
TI  - [Psychosomatic problems of certain backaches].

PMID- 15429722
TI  - [Congenital dislocation of the hip treated by surgical reduction and replacement
      of the femoral head with ossacryl].

PMID- 15429723
TI  - [Foreign bodies of the duodenum].

PMID- 15429724
TI  - [Fistulous tibio-tarsal white tumor; treatment by resection and streptomycin].

PMID- 15429725
TI  - [Hepatic lobectomy].

PMID- 15429726
TI  - [Pulmonary arteriovenous aneurysms].

PMID- 15429727
TI  - [Non-surgical treatment of perforated ulcers].

PMID- 15429728
TI  - [Death of Heitz-Boyer, former president of the Academie de chirurgie].

PMID- 15429729
TI  - [Case of acute lithiasic cholecystitis of children].

PMID- 15429730
TI  - [Case of rupture and spontaneous hematoma of the external oblique abdominal
      muscle].

PMID- 15429731
TI  - [Bazy-Galtier operation in Madelung deformity].

PMID- 15429732
TI  - [Functional reeducation in traumatology].

PMID- 15429733
TI  - [Surgical reposition with arthroplasty in the treatment of inveterate high
      congenital dislocations in adults].

PMID- 15429734
TI  - [Use of trichloroacetic acid (Darcissac method) in pulmonary surgery].

PMID- 15429735
TI  - [Pyloric stenosis due to ingestion of a caustic].

PMID- 15429736
TI  - [Rehabilitation of patients with osteoarthritic tuberculosis].

PMID- 15429737
TI  - [Resection-reconstruction of the hip in inveterate congenital dislocation in
      adults].

PMID- 15429739
TI  - [Development of personal technic of aseptic gastrectomy].

PMID- 15429738
TI  - [Foreign bodies of the duodenum].

PMID- 15429740
TI  - [Cancer of the cervix in phase I. 1. Local sterilization by radium-therapy;
      remote results of radium-therapy and of radium and surgery. 2. Study of external
      and internal iliac adenopathies].

PMID- 15429741
TI  - [Bone grafts preserved by refrigeration; results and indications].

PMID- 15429742
TI  - [Present orientation of the surgical therapy of pulmonary tuberculosis; mechanism
      of action, technic and results].

PMID- 15429743
TI  - [Present orientation of the surgical treatment of pulmonary tuberculosis].

PMID- 15429744
TI  - [Epibronchial diverticulum of the esophagus].

PMID- 15429745
TI  - [Spontaneous hematoma of the abdominal wall].

PMID- 15429746
TI  - [Grafts of dead bone and homoplastic and heteroplastic grafts].

PMID- 15429747
TI  - [Cardio-pericardiopexis, Thompson method, for the treatment of coronaritis and
      angina pectoris; one case study of results in New York during the past 12 years].

PMID- 15429748
TI  - [Septicemia treated by excision of a femoral arteriovenous aneurysm].

PMID- 15429749
TI  - [Attitude of the hand and fingers similar to the Volkmann syndrome, following
      osteomyelitis of the forearm].

PMID- 15429750
TI  - [Blood banks].

PMID- 15429751
TI  - [Treatment of perforated ulcers by aspiration].

PMID- 15429752
TI  - [Operative intervention or nonintervention with continuous aspiration in
      perforated gastroduodenal ulcers].

PMID- 15429753
TI  - [A case of mummified epithelioma on the dorsum of the foot in a young adult].

PMID- 15429754
TI  - [Definition and fate of free grafts].

PMID- 15429755
TI  - [Free grafts].

PMID- 15429756
TI  - [Case of typhoid osteitis treated with chloromycetin].

PMID- 15429757
TI  - [Exposure of the ureters in extended transperineal colpo-hysterectomy for cancer
      of the cervix].

PMID- 15429758
TI  - [Surgical treatment of essential scoliosis].

PMID- 15429759
TI  - [Extraction of bullets from the vascular bundle of the heart (inter-aortico
      caval), from the left ventricle, and from the right ventricle].

PMID- 15429760
TI  - [Technic to follow in subdural hematomas of traumatic origin operated on later
      than the 10th or 12th day following the accident].

PMID- 15429761
TI  - [Double cancer of the greater curvature of the stomach and of the lower third of
      the esophagus; palliative esophagojejunostomy by the Rienhoff process].

PMID- 15429762
TI  - [Homoplastic graft in a burned child].

PMID- 15429763
TI  - Aggression in relation to emotional development, normal and pathological.

PMID- 15429764
TI  - Psychiatric service in relation to public-health activities.

PMID- 15429765
TI  - Personality factors in vocational rehabilitation.

PMID- 15429766
TI  - I wrote about dogs; a mental-hygiene note.

PMID- 15429767
TI  - Fifty years of the juvenile-court movement in the United States.

PMID- 15429768
TI  - Basic attitudes and goals of the therapist.

PMID- 15429769
TI  - Camping for disturbed children.

PMID- 15429770
TI  - Modern dynamics of rehabilitation for the psychotic patient.

PMID- 15429771
TI  - Mental hygiene in the day's work; a day in the life of a group worker in the
      recreation-education field.

PMID- 15429772
TI  - A day in the life of a police officer.

PMID- 15429773
TI  - A day in the life of the teacher.

PMID- 15429774
TI  - In memoriam: Adolph Meyer.

PMID- 15429775
TI  - In memoriam: Horatio Milo Pollock.

PMID- 15429776
TI  - A survey of nutritional status among school children and their response to
      nutrient therapy.

PMID- 15429777
TI  - Changes in blood values during pregnancy and the relation of protein levels to
      toxemia symptoms.

PMID- 15429778
TI  - The United States "Point Four" Program.

PMID- 15429779
TI  - Population increase and manpower utilization in imperial Japan.

PMID- 15429780
TI  - Social and psychological factors affecting fertility; fertility planning and
      fertility rates by religious interest and denomination.

PMID- 15429781
TI  - Rehabilitation of the amputee.

PMID- 15429782
TI  - Organization and administration of neuropsychiatry in the Office of the Surgeon
      General, 1942-1947.

PMID- 15429783
TI  - Panarteritis nodosa; a brief review of the recent literature; report of a case
      with antemortem diagnosis and interesting findings at necropsy.

PMID- 15429784
TI  - Psychological principles and military leadership.

PMID- 15429785
TI  - A new contact bone plate.

PMID- 15429786
TI  - Osteoma complicated by myositis ossificans: a case report.

PMID- 15429788
TI  - Sojourn in Zamboanga; monkey business, juramentados, white "king" of the Moros.

PMID- 15429787
TI  - Report of a case of an ununited intratrochanteric fracture of the femur; its
      subsequent treatment and results.

PMID- 15429789
TI  - Blood transfusion experience of the Veterans Administration, July 1, 1948-July 1,
      1949.

PMID- 15429790
TI  - Procedure in clinical research.

PMID- 15429791
TI  - The tuberculosis control program of the U.S. Veterans Administration.

PMID- 15429792
TI  - Poliomyelitis: an hypothesis of its etiology.

PMID- 15429793
TI  - Recent trends in prostatic surgery.

PMID- 15429794
TI  - Polyphasic surgery.

PMID- 15429795
TI  - Tests to determine suitability of burnt coral as a dentifrice: report I.

PMID- 15429796
TI  - Tests to determine suitability of fresh coral as a dentifrice: Report II.

PMID- 15429798
TI  - Ano-rectal fibrosis.

PMID- 15429797
TI  - Focal infection with systemic manifestations; a case history.

PMID- 15429799
TI  - Evaluation of oral priscoline as an antipruritic agent.

PMID- 15429800
TI  - Sojourn in Zamboanga; joint operation "Pasananca," Joloanian holiday, the legend
      of Fort Pilar.

PMID- 15429801
TI  - GERMAN aviation medicine.

PMID- 15429802
TI  - [Unfavorable results of Pestalozza's pelvic hysteropexy].

PMID- 15429803
TI  - [Examination of the autonomic nervous system with Breitman's test in parturition
      and in puerperium].

PMID- 15429804
TI  - [Use and action of curare in parturition].

PMID- 15429805
TI  - [Desoxycorticosterone in the disturbances of radium therapy].

PMID- 15429806
TI  - [A case of acute invagination of the right oviduct].

PMID- 15429807
TI  - [Catamenial and progenital herpes simplex, treatment].

PMID- 15429808
TI  - [Ten "commandments" of the gynecologist for control of cancer of the genitals].

PMID- 15429809
TI  - [Medical prescriptions for Camille].

PMID- 15429810
TI  - [The water of the Queen of Hungary].

PMID- 15429811
TI  - [Sensitivity of different forms of primary pulmonary tuberculosis to
      streptomycin; study of 155 cases: considerations and research].

PMID- 15429812
TI  - [Transfusional reactions and endovenous procaine].

PMID- 15429813
TI  - [Oral administration of penicillin in pediatrics; importance of simultaneous
      administration of a buffer substance or of nephrostasin].

PMID- 15429814
TI  - [Chloromycetin in the gastroenteric syndromes of infants].

PMID- 15429816
TI  - Advantages and limitations of the quantitative VDRL slide test.

PMID- 15429815
TI  - [Puberal evolution in subjects who had hypertrophy of the thymus in early
      infancy].

PMID- 15429817
TI  - The clinical application of quantitative reports of serologic tests for syphilis.

PMID- 15429818
TI  - Progress in maternal and infant health in Minnesota: a statistical study of the
      decade 1939-1949.

PMID- 15429819
TI  - Solitary pyogenic liver abscess; review of literature and report of case.

PMID- 15429820
TI  - Subfascial fat abnormalities and low back pain.

PMID- 15429821
TI  - Hemolytic transfusion reaction in obstetrics; report of case.

PMID- 15429822
TI  - Placental polyp simulating a chorionepithelioma; report of case.

PMID- 15429823
TI  - Medicine and its practitioners in Olmsted County prior to 1900.

PMID- 15429824
TI  - The postthrombotic syndrome.

PMID- 15429825
TI  - Venography in the postphlebitic syndrome.

PMID- 15429826
TI  - The return of "vein stripping".

PMID- 15429827
TI  - Fundamental principles in the treatment of varicose veins.

PMID- 15429828
TI  - Resume of present-day care and treatment of varicose veins and their
      complications.

PMID- 15429829
TI  - The emotional problems of the chronically ill.

PMID- 15429830
TI  - Hemangiopericytoma, an unusual extra rectal tumor.

PMID- 15429831
TI  - Clinical observations of experiments of nature.

PMID- 15429832
TI  - Tuberculosis in selectees disqualified for the army 1942-45; the record in
      Minnesota.

PMID- 15429833
TI  - An unusual type of pulmonary disease involving six members of a family.

PMID- 15429834
TI  - Acute inversion of the uterus; report of case.

PMID- 15429835
TI  - Paroxysmal tachycardia with attacks of unconsciousness; report of a case.

PMID- 15429836
TI  - Medicine and its practitioners in Olmsted County prior to 1900.

PMID- 15429837
TI  - Some practical questions in the diagnosis and treatment of diabetes mellitus.

PMID- 15429838
TI  - The management of the patient with hypertension.

PMID- 15429839
TI  - Suppurative diseases of the lungs and bronchi.

PMID- 15429840
TI  - Esophageal achalasia.

PMID- 15429841
TI  - Distinguished service oration on life of Dr. John Darrington.

PMID- 15429842
TI  - The phorias in clinical practice.

PMID- 15429844
TI  - Painful syndromes including the neuralgias.

PMID- 15429843
TI  - Progressive ulceration of the abdominal wall--amoebiasis cutis.

PMID- 15429845
TI  - Suprapubic prostatectomy with primary closure of the bladder.

PMID- 15429846
TI  - Removal of children's tonsils and adenoids.

PMID- 15429847
TI  - Essence of the mid-century physician, his today and his tomorrow.

PMID- 15429848
TI  - Results of treatment of hyperthyroidism with propylthiouracil and thiouracil.

PMID- 15429849
TI  - Danger of leukemia transmission by blood transfusion.

PMID- 15429850
TI  - The no man's range of normal blood pressure; based on biometric charts of 6,500
      readings over 20 years (1928-1948).

PMID- 15429851
TI  - Periarteritis nodosa; a review of the literature.

PMID- 15429852
TI  - Subhepatic cecum and appendix.

PMID- 15429853
TI  - To get recruitment results local effort must be added to national promotion.

PMID- 15429854
TI  - A day in the life of a record librarian.

PMID- 15429855
TI  - Corridor cut-offs provide flexibility in this hospital.

PMID- 15429856
TI  - Patient identification made positive.

PMID- 15429857
TI  - Easton's experience with polio proves that a hospital can be self-sufficient in
      an epidemic.

PMID- 15429858
TI  - These tests help the hospital to measure nursing quality.

PMID- 15429859
TI  - Punch card accounting lightens the loan of paper work.

PMID- 15429860
TI  - Televised clinics are as useful for teaching medicine as they are for teaching
      surgery.

PMID- 15429861
TI  - The hospital runs smoothly on a plan of the day.

PMID- 15429862
TI  - Mr. Administrator, R. N.

PMID- 15429863
TI  - Blue Cross drive in Leavenworth brought the whole community into the act.

PMID- 15429864
TI  - Strictly central service is provided for this 100 bed hospital that serves
      Comanche County, Oklahoma.

PMID- 15429865
TI  - Take them young and make their parents happy with a photograph.

PMID- 15429866
TI  - Safety concerns everyone in the hospital.

PMID- 15429867
TI  - SPECIAL problems of religious hospitals studied at Catholic convention.

PMID- 15429868
TI  - Visual aids to in-service training of staff and employees.

PMID- 15429869
TI  - Only cooperation can prevent socialization.

PMID- 15429870
TI  - Modern inhalation therapy; organization of service.

PMID- 15429871
TI  - The responsibility of the medical center to the family physician.

PMID- 15429872
TI  - How miracle drugs are born.

PMID- 15429873
TI  - Tableware, 1950.

PMID- 15429874
TI  - Nutritious main dishes give substance to meals.

PMID- 15429875
TI  - Menus for August 1950.

PMID- 15429877
TI  - How the housekeeping department can help to make the hospital a zone of quiet.

PMID- 15429876
TI  - Fire extinguishers, their selection, maintenance and use.

PMID- 15429878
TI  - [Antibiotics in the treatment and prognosis of uterine perforation; observations
      on the use of associated penicillin and streptomycin].

PMID- 15429879
TI  - [Provocation of sterility in the rabbit by means of the administration of urine
      of pregnant women].

PMID- 15429880
TI  - [Mechanism of action of male sex hormones in menometrorrhagia].

PMID- 15429881
TI  - [Note on the clinical aspect and therapy of pelvic congestion].

PMID- 15429882
TI  - The etiologic aspects of anemia.

PMID- 15429883
TI  - Early diagnosis of malignancies of the breast.

PMID- 15429885
TI  - Early diagnosis of malignancy of the stomach and colon.

PMID- 15429884
TI  - Early diagnosis of malignancies of the cervix and uterus.

PMID- 15429886
TI  - Early diagnosis of malignancies; laboratory aids.

PMID- 15429887
TI  - Early diagnosis of carcinoma of the stomach and colon.

PMID- 15429888
TI  - The significance of anxiety.

PMID- 15429889
TI  - Diagnosis and treatment of minor lesions of the urethra and bladder in women.

PMID- 15429890
TI  - Radiation treatment of tonsils, adenoids, and sinuses.

PMID- 15429891
TI  - Cardiac problems of geriatrics.

PMID- 15429892
TI  - Aureomycin.

PMID- 15429893
TI  - Radical surgery for cancer.

PMID- 15429894
TI  - [Neurosurgical therapy of psychoses].

PMID- 15429895
TI  - [Incomplete form of total congenital color blindness].

PMID- 15429896
TI  - [A simple inexpensive and efficient method of preparing dysentery, typhoid and
      paratyphoid feces for dispatch to the laboratory].

PMID- 15429897
TI  - [Experience with therapeutic use of parpanit].

PMID- 15429898
TI  - [Adaline toxicoderma with clinical aspect of Gougerot-Blum's pigmented purpuric
      lichenoid dermatitis].

PMID- 15429899
TI  - [Modern surgery and its results].

PMID- 15429900
TI  - [In memoriam Dr. Clifford Dobell, F.R.S. (1886-1949)].

PMID- 15429901
TI  - [Gerard van Swieten as reformer of the Vienna Medical Faculty].

PMID- 15429902
TI  - [The medical school at Hoorn].

PMID- 15429903
TI  - [Dysentery transmitted through cheese].

PMID- 15429904
TI  - [Relation between Jensen's chorioretinitis and toxoplasmosis].

PMID- 15429905
TI  - [Keratoconus].

PMID- 15429906
TI  - [Hypertonic choroiditis and vascular necrosis].

PMID- 15429907
TI  - [Explanation of vision according to the quantum theory].

PMID- 15429908
TI  - [A movable artificial eye].

PMID- 15429909
TI  - [Carbide injury of the cornea].

PMID- 15429910
TI  - [Haziness of the cornea as a result of dehydration, and related conditions].

PMID- 15429911
TI  - [Increasing resistance of micro-organisms to penicillin and streptomycin during
      treatment].

PMID- 15429912
TI  - [Treatment of a few forms of retinal detachment].

PMID- 15429913
TI  - [Megalocornea-cataract].

PMID- 15429914
TI  - [Simple methods of measurement with the slit lamp].

PMID- 15429915
TI  - [Pterygium and pinguecula as signs of old age].

PMID- 15429916
TI  - [Orbital tension in Cushing's disease].

PMID- 15429917
TI  - [Surgical therapy of angina pectoris].

PMID- 15429918
TI  - [Treatment of Kahler's disease with stilbamidine].

PMID- 15429919
TI  - [Cardiolipin as a reagent in the Wassermann and other serological tests for
      syphilis].

PMID- 15429920
TI  - [Surgical therapy of uterine prolapse with modified Le Fort operation].

PMID- 15429921
TI  - [Preparations of penicillin for retarded action].

PMID- 15429922
TI  - [Atypical subcutaneous tuberculous infiltration in an infant].

PMID- 15429923
TI  - [Toxoplasmosis with functional disorder of the bone marrow].

PMID- 15429924
TI  - [Smallpox epidemic in the Glasgow hospital].

PMID- 15429925
TI  - [Problems of narcissism].

PMID- 15429926
TI  - [Narcissism].

PMID- 15429927
TI  - [Trip to America for the purpose of studying the preoperative examination of
      Fallot's tetralogy].

PMID- 15429928
TI  - [Critical observations on Spitzer's theory].

PMID- 15429929
TI  - [Congenital cardiac abnormality (left-to-right shunt)].

PMID- 15429930
TI  - [Roentgenological findings in aortic stenosis].

PMID- 15429931
TI  - [Cholecystectomy].

PMID- 15429932
TI  - [Intestinal apoplexy].

PMID- 15429933
TI  - [Investigation of a remarkable strain of Mycobacterium tuberculosis].

PMID- 15429934
TI  - [Symptomatic hemolytic anemia in a case of nonreactive generalized tuberculosis].

PMID- 15429935
TI  - [Observations on lower-limb amputation and prosthetic measurement].

PMID- 15429936
TI  - [Tuberculosis among sanatorium personnel with and without BCG vaccination].

PMID- 15429937
TI  - [Differential diagnosis of pemphigus vulgaris and dermatitis herpetiformis].

PMID- 15429938
TI  - [Poisoning by Amanita phalloides].

PMID- 15429939
TI  - [Hyperkeratosis follicularis and corneal degeneration].

PMID- 15429940
TI  - [Results of some modern operations for glaucoma].

PMID- 15429941
TI  - [Pseudoglioma].

PMID- 15429942
TI  - [Congenital, familial ptosis, combined with other congenital defects of the
      oculomotor musculature].

PMID- 15429943
TI  - Multiple-balloon kymographic recording of the comparative action of oral
      administration of atropine, tincture of belladonna and placebos on the motility
      of the upper small intestine in man.

PMID- 15429944
TI  - Dermatologic clues in surgical diagnosis.

PMID- 15429945
TI  - True renal-artery aneurysm; report of a case.

PMID- 15429946
TI  - A corrective shoe for toe drop.

PMID- 15429947
TI  - Abdominal surgery.

PMID- 15429948
TI  - WEEKLY clinicopathological exercises; atrophy of anterior lobe of pituitary body,
      severe, with hypopituitarism; atrophy of thyroid gland and adrenal cortex.

PMID- 15429949
TI  - WEEKLY clinicopathological exercises; multiple myeloma; nephrosclerosis;
      arteriosclerosis; pulmonary edema; bronchopneumonia.

PMID- 15429951
TI  - The pathogenesis and treatment of uremia.

PMID- 15429950
TI  - Recent advances in the treatment of malignancy.

PMID- 15429952
TI  - Practical applications of recent advances in genetics to clinical problems.

PMID- 15429953
TI  - The psychosomatic character.

PMID- 15429954
TI  - Minimal spinal anesthesia for cesarean section.

PMID- 15429955
TI  - A comparison of the malleable needle and catheter technics for continuous spinal
      anesthesia.

PMID- 15429956
TI  - Anesthesia for emergency surgery following massive upper gastrointestinal
      bleeding.

PMID- 15429957
TI  - A method of splinting the hand and fingers.

PMID- 15429959
TI  - Results of sympathectomy in diabetic arteriosclerotic peripheral vascular
      disease.

PMID- 15429958
TI  - Heart disease and industrial medicine; recent trends in the evaluation of the
      cardiac worker.

PMID- 15429960
TI  - The treatment of pruritus with adenosine-5-monophosphate (muscle adenylic acid).

PMID- 15429961
TI  - Pituitary myxedema with autopsy findings.

PMID- 15429962
TI  - Small bowel obstruction due to a phytobezoar.

PMID- 15429963
TI  - Successful medical treatment of obstructive hydrocephalus in tuberculous
      meningitis.

PMID- 15429964
TI  - Gallstone ileus.

PMID- 15429965
TI  - Thyrotoxicosis complicating pregnancy.

PMID- 15429966
TI  - Tetanus resulting from a foreign body in the nose.

PMID- 15429967
TI  - Leukemia occurring in man and wife.

PMID- 15429968
TI  - Pulmonary moniliasis associated with carcinoma of the lung.

PMID- 15429969
TI  - Responsibility of hospitals to doctors in the community.

PMID- 15429970
TI  - Membership in Blue Shield plans exceeds 2 and a quarter million.

PMID- 15429971
TI  - The precancerous dermatoses.

PMID- 15429972
TI  - Advantages and disadvantages of caudal analgesia; experience in 2,000 cases.

PMID- 15429973
TI  - Postpartum sterilization.

PMID- 15429974
TI  - Unilateral twin ectopic pregnancy; case report.

PMID- 15429975
TI  - Bulbo-respiratory poliomyelitis and its treatment.

PMID- 15429976
TI  - Diabetes as a public health problem.

PMID- 15429977
TI  - Meningocele following hemilaminectomy; report of 2 cases.

PMID- 15429978
TI  - A femoral hernia containing a strangulated appendix preoperatively diagnosed as a
      metastatic lymph node.

PMID- 15429979
TI  - PHYSICIANS of North Carolina; the DeRosset family.

PMID- 15429980
TI  - Clinicopathologic conference; generalized muscular degeneration, cutaneous
      atrophy, and edema and perivascular lymphocytic infiltration in the cutis
      (dermatomyositis).

PMID- 15429981
TI  - Growth of neurotropic viruses in extraneural tissues; preliminary report on the
      propagation of poliomyelitis virus (Lansing and Hof. strains) in cultures of
      human testicular tissue.

PMID- 15429982
TI  - Pregnancy complicating Hodgkin's disease.

PMID- 15429983
TI  - Improved tidal irrigator.

PMID- 15429984
TI  - Treatment of chronic brucellosis with aureomycin.

PMID- 15429986
TI  - Hoarseness.

PMID- 15429985
TI  - The blind baby.

PMID- 15429987
TI  - Insulin and insulin mixtures.

PMID- 15429988
TI  - [Masked diseases of stomatological origin].

PMID- 15429990
TI  - [Antero-inferior dystrophic paradentitis due to compression of crowded teeth].

PMID- 15429989
TI  - [Antibiotics, with particular reference to their application in stomatology].

PMID- 15429991
TI  - [Polyvalent anaerobic vaccinotherapy in marginal periodontal diseases].

PMID- 15429992
TI  - Anti-social behaviour in adolescents.

PMID- 15429993
TI  - TWO aspects of industrial nursing.

PMID- 15429994
TI  - NURSING assistants in mental hospitals; new salary scales and Scottish grading.

PMID- 15429995
TI  - TRAINING within industry on the district; district bag technique.

PMID- 15429996
TI  - MATERNITY unit, St. John & St. Elizabeth Hospital, London.

PMID- 15429997
TI  - Psychological approach to pregnancy and labour.

PMID- 15429998
TI  - The hazards of medical procedure; bronchoscopy.

PMID- 15429999
TI  - Hermaphroditism and its treatment.

PMID- 15430000
TI  - The hazards of medical procedures; miscellaneous operations involving risks.

PMID- 15430001
TI  - Aftercare of the hospital patient.

PMID- 15430002
TI  - Mesenteric thrombosis and duodenal ulcer.

PMID- 15430003
TI  - Training within industry on the district; cleaning the mouth of an unconscious
      patient.

PMID- 15430005
TI  - EMPLOYMENT relations surveyed in a group of hospitals in the Wirral.

PMID- 15430004
TI  - SCOTTISH Pre-Nursing School at Dean College, Edinburgh.

PMID- 15430006
TI  - Perineal trauma.

PMID- 15430007
TI  - The modern trend in social medicine in the home and in industry.

PMID- 15430008
TI  - PSYCHIATRIC nursing, a challenge and an invitation.

PMID- 15430009
TI  - MAUDSLEY Hospital, a hospital for the treatment of psychiatric disorders.

PMID- 15430010
TI  - Medical problems in coalmining; the problems and hazards of the underground
      worker.

PMID- 15430011
TI  - The modern trend in social medicine in the home and in industry.

PMID- 15430012
TI  - The General Nursing Council for England and Wales--its organisation and work.

PMID- 15430013
TI  - Problems raised by kwashiorkor.

PMID- 15430014
TI  - EFFECT of protein level on the amino acid requirements of chicks.

PMID- 15430015
TI  - VITAMIN B12 and the intrinsic factor.

PMID- 15430016
TI  - DIET and industrial performance.

PMID- 15430017
TI  - TOXIC factor of agenized flour--a methionine antimetabolite?

PMID- 15430018
TI  - DIETARY standards and nutrition education in Canada.

PMID- 15430019
TI  - ADRENAL in protein and carbohydrate metabolism.

PMID- 15430020
TI  - ATHEROSCLEROSIS and serum cholesterol fractions.

PMID- 15430021
TI  - "TRACE" mineral requirements.

PMID- 15430022
TI  - NUTRITION of animal cells in tissue culture.

PMID- 15430024
TI  - DIET and aging.

PMID- 15430023
TI  - PYRIDOXINE deficiency in man.

PMID- 15430025
TI  - VITAMIN B12 and gizzard erosions in chicks.

PMID- 15430026
TI  - VITAMIN A in the nephrotic syndrome.

PMID- 15430027
TI  - UPTAKE of radioactive calcium by the hen's egg.

PMID- 15430028
TI  - Autogenous allergy and the reproductive function; a review and preliminary
      report.

PMID- 15430029
TI  - Fluid and electrolyte balance in gynecologic surgery.

PMID- 15430030
TI  - Female gonadal dysfunction; survey of its background, its clinical
      manifestations, its rational treatment.

PMID- 15430031
TI  - Music as an adjunct in the training of children with cerebral palsy.

PMID- 15430032
TI  - Work evaluation in rehabilitation.

PMID- 15430033
TI  - Neuromuscular re-education in the rehabilitation of cerebral palsy.

PMID- 15430034
TI  - Some principles to be followed in the prevention of contractures.

PMID- 15430035
TI  - Selection of music to accompany electroshock therapy.

PMID- 15430036
TI  - Foramen magnum and high cervical cord lesions simulating degenerative disease of
      the nervous system.

PMID- 15430037
TI  - The emergency management of acute, massive upper gastrointestinal hemorrhage.

PMID- 15430038
TI  - Clinical significance and management of the hypasthenic patient.

PMID- 15430039
TI  - Contact dermatitis due to cinnamon.

PMID- 15430040
TI  - The treatment of thrombo-embolic disease.

PMID- 15430041
TI  - The use of CO2 in inhalation therapy.

PMID- 15430042
TI  - Full-term intra-abdominal pregnancy.

PMID- 15430043
TI  - Hygiene of pregnancy.

PMID- 15430044
TI  - Culture is based on history; and history is based upon the written word.

PMID- 15430045
TI  - HARMONIOUS 53rd AOA Congress applauds practice rules, election of Dr. White.

PMID- 15430046
TI  - Myopia from an operational viewpoint.

PMID- 15430047
TI  - OPTOMETRIC schools association helps IBB to settle educational problems.

PMID- 15430048
TI  - PERTINENT AOA resolutions.

PMID- 15430049
TI  - Acute infections about the face and jaws.

PMID- 15430050
TI  - Peripheral osteotomy with tantalum gauze inserts for large mandibular tumors.

PMID- 15430051
TI  - Principles and technique of exodontia; inferior third molars.

PMID- 15430052
TI  - Dentigerous cysts of the jaws with unerupted teeth.

PMID- 15430053
TI  - Mandibular dentigerous cyst; report of a case.

PMID- 15430054
TI  - Bilateral fracture of the anterior part of the mandible; reduction with
      intermaxillary traction and fixation with an acrylic splint; report of a case.

PMID- 15430055
TI  - The development of physiologic gingival contours by gingivoplasty.

PMID- 15430056
TI  - Recent advances in diagnosis and treatment of diseases of the chest.

PMID- 15430057
TI  - Contagious chest diseases, a problem in the practice of dentistry.

PMID- 15430058
TI  - Significance of correct processing in intraoral roentgenography.

PMID- 15430059
TI  - [Medical thoughts].

PMID- 15430060
TI  - [Not Available].

PMID- 15430061
TI  - [Treatment of hyperthyroidism with male hormones].

PMID- 15430062
TI  - [Post abortum septicemia due to Bacillus perfringens; cure by exchange
      transfusion and peritoneal dialysis].

PMID- 15430064
TI  - [Tuberculosis in 1950].

PMID- 15430063
TI  - [Syphilitic hemiplegia; specific treatment begun in the 6th year; considerable
      recovery].

PMID- 15430065
TI  - [Relapse of miliary tuberculosis after streptomycin therapy and caseous re
      seeding foci].

PMID- 15430066
TI  - [The problem of cavitary distention in the light of streptomycin therapy].

PMID- 15430067
TI  - [Treatment of tuberculosis by sulfones].

PMID- 15430068
TI  - [Dermatology and syphilography in 1950].

PMID- 15430069
TI  - [Lupus erythematosus and allergids; general practical and therapeutic
      consequences].

PMID- 15430070
TI  - [New treatment of the minor venereal diseases: chancroid Nicolas-Favre disease
      and granuloma inguinal].

PMID- 15430071
TI  - [Synovial pseudo-cysts of the skin].

PMID- 15430072
TI  - [Cardiac disorders provoked by phlebitis].

PMID- 15430073
TI  - [Present treatment of scleroderma].

PMID- 15430074
TI  - [Evolution of the effusion in 28 cases of purulent tuberculous pleurisy treated
      by hexomedine].

PMID- 15430075
TI  - [Ambulation after normal labor].

PMID- 15430076
TI  - [Obstetrics in 1949].

PMID- 15430077
TI  - [Uterine rupture during labor].

PMID- 15430078
TI  - [Malignant tumor of the inguinal region in a pregnant woman; endometrial origin].

PMID- 15430079
TI  - [Classic treatment of tuberculosis in 1950].

PMID- 15430080
TI  - [Treatment of typhoid by chloromycetin].

PMID- 15430081
TI  - [Decortication of the lung and tuberculosis].

PMID- 15430082
TI  - [Not Available].

PMID- 15430083
TI  - [Diseases of the respiratory tract].

PMID- 15430084
TI  - [Large suppurative pulmonary cysts; purulent pseudo-pleurisy].

PMID- 15430085
TI  - [Biological diagnosis of asthma and therapeutic deductions].

PMID- 15430086
TI  - [Sternberg's leukosarcomatosis].

PMID- 15430087
TI  - [Lymphoid leukemia and pulmonary cancer].

PMID- 15430088
TI  - [Responsibility of the surgeons and the consent of the patients].

PMID- 15430089
TI  - [Fractionated hemodialysis with Kolff's artificial kidney].

PMID- 15430090
TI  - [Implantations of stilbestrol in the treatment of rheumatism].

PMID- 15430091
TI  - [Not Available].

PMID- 15430092
TI  - [Role of viruses in the production of cancer].

PMID- 15430093
TI  - [Cancer and artificial radio-elements].

PMID- 15430094
TI  - [Esophageal localizations of Hodgkin's disease].

PMID- 15430095
TI  - [Treatment of intolerable pain by transorbital lobotomy].

PMID- 15430096
TI  - [Ambulatory treatment of hemorrhoids by sclerosing injections of an oil solution
      of phenic acid].

PMID- 15430097
TI  - [Early diagnosis of tuberculous osteoarthritis in the young adult].

PMID- 15430098
TI  - [Study of the antecedents of the primary complex in pulmonary tuberculosis].

PMID- 15430099
TI  - [Treatment of arterial hypertension by sulfocynates and vitamins A and K].

PMID- 15430100
TI  - Endocrine homeostasis in clinical pediatrics.

PMID- 15430101
TI  - Congenital anomalies of the esophagus.

PMID- 15430102
TI  - Angiocardiography in infants and children; new technic.

PMID- 15430103
TI  - Recovery from influenzal meningitis without intrathecal therapy in a four day old
      infant.

PMID- 15430104
TI  - 677 congenitally malformed infants and associated gestational characteristics;
      general considerations.

PMID- 15430105
TI  - Favism in two children in California.

PMID- 15430106
TI  - Physiologic and chemical response of premature infants to oxygen-enriched
      atmosphere.

PMID- 15430107
TI  - Does glutamic acid administration influence mental function?

PMID- 15430108
TI  - Postinfantile cortical hyperostosis with subdural hematoma; report of case and
      review of the literature.

PMID- 15430109
TI  - Absorption of fat and vitamin A in premature infants; effect of different levels
      of fat intake on the retention of fat and vitamin A.

PMID- 15430110
TI  - Determination of the oxygen content of capillary blood in congenital heart
      disease.

PMID- 15430111
TI  - Diastematomyelia (congenital clefts of the spinal cord); diagnosis and surgical
      treatment.

PMID- 15430112
TI  - Tularemia as a pediatric problem.

PMID- 15430113
TI  - Hypercalcemia nephropathy and encephalopathy following immobilization; case
      report.

PMID- 15430114
TI  - [Pathogenesis and prevention of complications in scarlet fever].

PMID- 15430115
TI  - [Development of diphtheric infection in animals following a single inoculation
      with native anatoxin].

PMID- 15430116
TI  - [Pathology and morphology of the vascular and connective tissues barriers in
      toxic states].

PMID- 15430117
TI  - [Modification of erythrocytes in various stages of scarlet fever].

PMID- 15430118
TI  - [Cardiovascular disorders in toxic diphtheria].

PMID- 15430119
TI  - [Lamliosis in etiology of chronic enterocolitis in young children in Moscow and
      its therapy].

PMID- 15430120
TI  - [Health education; child's health protection].

PMID- 15430121
TI  - [Classification of clinical forms of diphtheria].

PMID- 15430122
TI  - Reduction of maternal mortality due to hemorrhage.

PMID- 15430123
TI  - The medical profession's role in public welfare.

PMID- 15430124
TI  - A decalogue for the early diagnosis of pelvic cancer.

PMID- 15430125
TI  - The surgical treatment of pancreatic and bile duct tumors.

PMID- 15430126
TI  - The medical aspects of atomic weapons.

PMID- 15430127
TI  - Clinical syndrome of hyperpotassemia and hypopotassemia.

PMID- 15430128
TI  - The diagnostic problems of gross hemorrhage from the upper gastro-intestinal
      tract.

PMID- 15430129
TI  - The surgical management of massive hemorrhage in peptic ulcer.

PMID- 15430130
TI  - The problem of the compound fracture.

PMID- 15430131
TI  - Thoracic injuries.

PMID- 15430132
TI  - Carcinoma of the esophagus.

PMID- 15430133
TI  - [Determining the hemolytic index of official medicinal drugs].

PMID- 15430134
TI  - [Heteroploid research on medicinal plants: Datura].

PMID- 15430135
TI  - [Stability of nicotylamid ampules].

PMID- 15430136
TI  - [Streptomycine and dihydrostreptomycine; determination and differentiation].

PMID- 15430137
TI  - Psychologic implications in poliomyelitis.

PMID- 15430138
TI  - Home care program for poliomyelitis patients.

PMID- 15430139
TI  - The drop pack for moist heat.

PMID- 15430140
TI  - A poliomyelitis survey in Los Angeles County.

PMID- 15430141
TI  - Treatment of bedsores in respirator patients.

PMID- 15430142
TI  - Physical therapy in state crippled children's programs.

PMID- 15430143
TI  - POLIO, 1949; Illinois and Massachusetts.

PMID- 15430144
TI  - SCHOOLS approved for training physical therapists.

PMID- 15430145
TI  - The health problem of America.

PMID- 15430146
TI  - Unique physical therapy department.

PMID- 15430147
TI  - Therapeutic exercise for pre and postoperative tuberculous thoracoplasty
      patients; a study of seventy patients.

PMID- 15430148
TI  - An improved shoulder wheel.

PMID- 15430149
TI  - The adrenal cortex and homoestasis.

PMID- 15430150
TI  - The 17-ketosteroids: their origin, determination and significance.

PMID- 15430151
TI  - Survival and revival of nervous tissues after arrest of circulation.

PMID- 15430152
TI  - Role of metal ions in enzyme systems.

PMID- 15430153
TI  - Hydrotherapy in physical treatment.

PMID- 15430154
TI  - Tissue heating by means of the inductothermy cable.

PMID- 15430155
TI  - Reduction by manipulation of impacted loose bodies in the knee joint.

PMID- 15430156
TI  - Organization for cerebral palsy.

PMID- 15430157
TI  - Science and physical medicine.

PMID- 15430158
TI  - Physiotherapy at the crossroads.

PMID- 15430159
TI  - Clinical and laboratory evaluation of G-11 (hexachlorophene) as a preoperative
      skin bacteriostatic agent.

PMID- 15430160
TI  - Growth of young human autogenous cartilage grafts.

PMID- 15430161
TI  - Transparent surgical drapes for the visualization of landmarks during operative
      procedures.

PMID- 15430162
TI  - Scientific use of colour to prevent surgical asthenopia.

PMID- 15430163
TI  - Breast malformations and a new approach to the problem of the small breast.

PMID- 15430164
TI  - A new instrument to be used in mammaplasty.

PMID- 15430166
TI  - The treatment of complicated plantar lesions.

PMID- 15430165
TI  - Repair of extensive palatal defects with skin tubes.

PMID- 15430167
TI  - Traumatic avulsion of skin of penis and scrotum; a simplified method of
      reconstruction.

PMID- 15430168
TI  - Microscopic guidance in the treatment of skin cancer.

PMID- 15430169
TI  - Fibroma of the palate.

PMID- 15430170
TI  - New type metal nasal splint.

PMID- 15430171
TI  - The surgical treatment of the bifid nose.

PMID- 15430172
TI  - Lessons of the postwar organization of plastic surgery in Europe.

PMID- 15430173
TI  - One stage surgical repair of gastroschisis (omphalocele) by cutis graft technic.

PMID- 15430174
TI  - Layer resection of cavernous hemangioma of the face followed by plastic
      restoration.

PMID- 15430175
TI  - Total pharyngoneoplasty.

PMID- 15430176
TI  - Medial cleft of the lower lip and mandible; a case report.

PMID- 15430177
TI  - Lateral facial clefts.

PMID- 15430178
TI  - Congenital cicatrix.

PMID- 15430179
TI  - The electro-dermatome.

PMID- 15430180
TI  - [Physiopathology and clinical diagnosis of ovarian follicles].

PMID- 15430181
TI  - [Cutaneous tuberculosis; treatment].

PMID- 15430182
TI  - [General principles in the diagnosis of infectious diseases].

PMID- 15430183
TI  - The anesthesiologist in the management of the surgical patient.

PMID- 15430184
TI  - Alcoholism and the general practitioner.

PMID- 15430185
TI  - Acute appendicitis complicating pregnancy.

PMID- 15430187
TI  - Medical management of thyroid disease.

PMID- 15430186
TI  - Tuberculin negative, histoplasmin positive, disseminated pulmonary calcification.

PMID- 15430188
TI  - Radioiodine in the treatment of thyrotoxicosis.

PMID- 15430189
TI  - Management of peptic ulcer.

PMID- 15430190
TI  - Carcinoma of the larynx.

PMID- 15430191
TI  - Rehabilitation of common neuromuscular disorders.

PMID- 15430192
TI  - Diseases of the nails.

PMID- 15430193
TI  - Xanthoma of the lung.

PMID- 15430194
TI  - Treatment of erysipelas.

PMID- 15430195
TI  - Management of food allergy.

PMID- 15430196
TI  - Treatment of air sickness.

PMID- 15430197
TI  - Necrotizing ulcerative gingivitis.

PMID- 15430198
TI  - Management of appendicitis.

PMID- 15430200
TI  - Favourite prescriptions.

PMID- 15430199
TI  - Men of medicine: Dr. John from the hills.

PMID- 15430201
TI  - Favourite prescriptions in general practice.

PMID- 15430202
TI  - Favourite prescriptions in pulmonary diseases.

PMID- 15430203
TI  - Favourite prescriptions in diseases of the nervous system.

PMID- 15430204
TI  - Favourite prescriptions in skin diseases.

PMID- 15430205
TI  - Favourite prescriptions in diseases of the ear, nose and throat.

PMID- 15430206
TI  - Favourite prescriptions in ophthalmology.

PMID- 15430207
TI  - Favourite surgical prescriptions.

PMID- 15430208
TI  - Diseases of domesticated animals constituting a hazard to mankind.

PMID- 15430209
TI  - Digitalis and strophanthus.

PMID- 15430210
TI  - Current therapeutics; vitamin B12.

PMID- 15430211
TI  - The diagnosis of jaundice.

PMID- 15430212
TI  - Epistaxis.

PMID- 15430213
TI  - The emergency treatment of toothache.

PMID- 15430214
TI  - [Acute rheumatoid polyarthritis and rheumatic dermatitis in childhood].

PMID- 15430215
TI  - [Paget disease of bone].

PMID- 15430216
TI  - [Subcutaneous smallpox vaccination for it general practitioner].

PMID- 15430217
TI  - [Experience with intravenous salicyl therapy].

PMID- 15430218
TI  - [Problem of sunburn prophylaxis and sun tan].

PMID- 15430219
TI  - [Fundamentals, technic and results of thoracoplasty with apicolysis].

PMID- 15430220
TI  - [The esophageal propagation of gastric cancer; its clinico-surgical importance].

PMID- 15430221
TI  - [Complete course of allergic diseases presented at the Allergy Service of the
      Hospital Rivadavia; anamnesis and examination of allergic patients].

PMID- 15430223
TI  - [Volvulus of the stomach; its radiological picture].

PMID- 15430222
TI  - [Therapeutic progress in internal medicine in 1949; cardiology].

PMID- 15430224
TI  - [Continuous peridural anesthesia in abdominal surgery].

PMID- 15430225
TI  - [Introduction to the study of fluorescence as a semeiological method of
      examination].

PMID- 15430226
TI  - [Notes on a tour through the United States 8 October to 12 December 1949].

PMID- 15430227
TI  - [Irritable tuberculous lung; inopportune therapeutic pneumothorax].

PMID- 15430228
TI  - [Facial paralysis; its therapeutic indications in accordance with the chronaxia
      diagnosis].

PMID- 15430229
TI  - [Fibroma of the stomach].

PMID- 15430230
TI  - [Complete course of allergic diseases presented in the Allergy Service of the
      Hospital Rivadavia; allergic manifestations of the upper respiratory tract].

PMID- 15430231
TI  - [Therapeutic progress in internal medicine; infectious diseases].

PMID- 15430232
TI  - [Notes on a tour through the United States].

PMID- 15430233
TI  - [Racemose cysticercosis of the posterior fossa; clinical and surgical
      considerations].

PMID- 15430234
TI  - [Mycotic bronchopneumopathies (pseudotuberculosis) in workers of the textile
      industry; its importance in industrial medicine].

PMID- 15430235
TI  - [Curarizing action of the venom of Elapidae].

PMID- 15430236
TI  - [Multiple hydatid cysts of the liver].

PMID- 15430237
TI  - [Technic of bronchography].

PMID- 15430238
TI  - [Treatment of diabetes mellitus].

PMID- 15430239
TI  - [Therapeutic progress in internal medicine during 1949; infectious diseases].

PMID- 15430240
TI  - [Notes on a trip through the U.S.A..].

PMID- 15430242
TI  - [Evolution of the treatment of puerperal infection].

PMID- 15430241
TI  - [Influence of streptomycin on tuberculin reaction; experimental and clinical
      study].

PMID- 15430243
TI  - [Curarizing action of the venom of Elapidae].

PMID- 15430244
TI  - [Syndrome of cardiac malformation and cerebral abscess].

PMID- 15430245
TI  - [Polyneuritis associated with nephritis].

PMID- 15430246
TI  - [First therapeutic experiences with the use of ultrasonic waves].

PMID- 15430247
TI  - [Therapeutic progress in internal medicine during 1949; diabetes, obesity, gout].

PMID- 15430249
TI  - [Surgical treatment of epilepsy].

PMID- 15430248
TI  - [Notes on a trip through the U.S.A..].

PMID- 15430250
TI  - [Vitamin A and B-carotene in liver diseases].

PMID- 15430252
TI  - [Intramedullary injection of a contrast substance for the diagnosis of bone
      diseases].

PMID- 15430251
TI  - [Growing importance of bacitracin].

PMID- 15430253
TI  - [Intolerance reactions in children].

PMID- 15430254
TI  - [Significance of the hemagglutination test in the diagnosis of tuberculosis and
      the control of BCG vaccination].

PMID- 15430255
TI  - [Frequency of the transmission of typhoid fever through butter; need for a
      campaign for pasteurized butter].

PMID- 15430256
TI  - [Lobotomy in psychopathic disorders].

PMID- 15430257
TI  - [Re-education of poliomyelitis patients: the motor picture].

PMID- 15430258
TI  - [Total field of vision and relative field of vision].

PMID- 15430259
TI  - [Disorders of the fat metabolism following transthoracic operation on the
      thoracic esophagus and the stomach].

PMID- 15430260
TI  - [The heart in obese subjects].

PMID- 15430261
TI  - [The present role of the children's sanatorium in the anti-tuberculosis
      campaign].

PMID- 15430262
TI  - [Behavior of the median lobe of the right lung with regard to tuberculosis].

PMID- 15430263
TI  - [Use of prostigmine in the treatment of heartburn in pregnant women].

PMID- 15430264
TI  - [Action of sodium salt of benzoyl-orthoxyparaaminobenzoic acid in urinary
      tuberculosis].

PMID- 15430265
TI  - [Recent data on diabetic coma; clinical aspect].

PMID- 15430266
TI  - [Old medical annuals].

PMID- 15430267
TI  - [Birth control in Japan to prevent over-population].

PMID- 15430268
TI  - [The bronchi during an asthma attack; experimental, bronchoscopic and
      anatomopathological study].

PMID- 15430269
TI  - [Action of synthetic chloramphenicol on the typhoid bacillus Eberthella typhosa
      studied by the phase contrast microscope].

PMID- 15430270
TI  - [Heterogenous vascular grafts; experimental study].

PMID- 15430271
TI  - [Periodic bimonthly fever with diffuse lesions of reticulosis].

PMID- 15430272
TI  - [Reaction of straightening the body axis in the newborn].

PMID- 15430273
TI  - [Not Available].

PMID- 15430274
TI  - [Melitensis cervical spondylarthritis].

PMID- 15430275
TI  - [General view of the cytodiagnosis of malignant epithelial tumors].

PMID- 15430276
TI  - [Experimental allergic encephalomyelitis].

PMID- 15430277
TI  - [Do deep varices exist? "downstream" and "upstream" phlebography].

PMID- 15430278
TI  - [Frontal tomography of the pituitary fossa in endocrinology].

PMID- 15430279
TI  - [Hyperinsulinism due to adenoma of the islands of Langerhans; adenectomy].

PMID- 15430280
TI  - [Therapeutic sub-cortical coagulations; topographic study of the ventricular
      system in relation to the central gray nuclei].

PMID- 15430281
TI  - [Attempts at endobronchial chrysotherapy in the treatment of tuberculous
      pulmonary cavities].

PMID- 15430282
TI  - [Study of the neuron and the new classification of the sympathetic nerve cells].

PMID- 15430283
TI  - [A new case of aortic-iliac embolism; embolectomy; therapy].

PMID- 15430284
TI  - [Radiological aspect of bone metastases of pelvic cancer].

PMID- 15430285
TI  - [20 cases of excision of the lung for tuberculosis].

PMID- 15430286
TI  - [Galli-Mainini reaction and determination of prolan B in pregnant women].

PMID- 15430288
TI  - [A case of chronic hiccups].

PMID- 15430287
TI  - [Malarial polyradiculoneuritis].

PMID- 15430290
TI  - [Reheating vat and stand for perfusion].

PMID- 15430289
TI  - [Not Available].

PMID- 15430291
TI  - [Case of radiculomedullary compression due to disease of the intervertebral
      disk].

PMID- 15430292
TI  - [Diagnosis of radiological opacities of the middle lobe of the lung].

PMID- 15430293
TI  - [A form of asthenic syndrome of deported persons and prisoners of war (1939-45);
      syndrome of late emotional paroxystic hypermnesia].

PMID- 15430294
TI  - [Arterial injections of procaine in peripheral infections].

PMID- 15430295
TI  - [Treatment of atonic wounds by local aerosol therapy].

PMID- 15430296
TI  - [Surgery in China yesterday and today].

PMID- 15430297
TI  - [Electrocardiography].

PMID- 15430298
TI  - [Phosphatases; importance of determination].

PMID- 15430299
TI  - [What is a "prostatic" and how to examine one?].

PMID- 15430300
TI  - [Ludwig's angina].

PMID- 15430301
TI  - [The public and the handicapped].

PMID- 15430302
TI  - [The public and the handicapped].

PMID- 15430303
TI  - [Prostheses after extensive amputation].

PMID- 15430304
TI  - [Austrian congress on care of the physically and mentally defective].

PMID- 15430306
TI  - [The cowl doesn't make the friar].

PMID- 15430305
TI  - [Care of the disabled in Sweden].

PMID- 15430307
TI  - [Length of institutional care].

PMID- 15430308
TI  - Studies on the mechanism of the oxygen effect on the radiosensitivity of
      Tradescantia chromosomes.

PMID- 15430309
TI  - The origin and behavior of mutable loci in maize.

PMID- 15430310
TI  - Generalized Eisenstein series and non-analytic automorphic functions.

PMID- 15430311
TI  - Arithmetical properties of polynomials associated with the lemniscate elliptic
      functions.

PMID- 15430312
TI  - A new type of self-sterility in plants.

PMID- 15430313
TI  - "Repeats" and the modern theory of the gene.

PMID- 15430314
TI  - Absence of mutagenic action of x-rayed cytoplasm in Habrobracon.

PMID- 15430315
TI  - A note on the exceptional Jordan algebra.

PMID- 15430316
TI  - On the singular values of a product of completely continuous operators.

PMID- 15430317
TI  - Some new functions of interest in x-ray crystallography.

PMID- 15430318
TI  - The work of the discovery committee.

PMID- 15430319
TI  - Wilkins lecture; Robert Hooke.

PMID- 15430320
TI  - A study of the component glycerides of cow and buffalo milk fats with reference
      to the possible mechanism of their production during lactation.

PMID- 15430321
TI  - The influence of geographic isolation on the skull of the green monkey
      (Cercopithecus aethiops sabaeus). I. A comparison between the teeth of the St
      Kitts and the African green monkey.

PMID- 15430322
TI  - The selective admission of antibodies to the foetus by the yolk-sac
      splanchnopleur in rabbits.

PMID- 15430323
TI  - The phosphorus metabolism of the brain.

PMID- 15430324
TI  - Does heat production precede mechanical response in muscular contraction?

PMID- 15430325
TI  - The series elastic component of muscle.

PMID- 15430326
TI  - The tonsil and adenoid problem.

PMID- 15430327
TI  - The tonsil problem.

PMID- 15430328
TI  - Current trends in the management of the gliomata.

PMID- 15430330
TI  - Obesity.

PMID- 15430329
TI  - Current trends in the management of the gliomata.

PMID- 15430331
TI  - Haemolytic disease of the newborn.

PMID- 15430332
TI  - Diabetes mellitus with obesity and acromegaly.

PMID- 15430333
TI  - Haemochromatosis.

PMID- 15430334
TI  - Acromegaly with diabetes mellitus and idiopathic skin lesions.

PMID- 15430335
TI  - Addison's disease and diabetes mellitus.

PMID- 15430337
TI  - Diabetes mellitus with thyrotoxicosis.

PMID- 15430336
TI  - Dwarfism, sexual infantilism, diabetes mellitus and anaemia.

PMID- 15430338
TI  - Hormone assays on body fluids.

PMID- 15430339
TI  - Males and females as anaesthetic risks.

PMID- 15430340
TI  - Clinical science applied to the problems of anaesthesia.

PMID- 15430341
TI  - Case for diagnosis. Dermatitis nodularis necrotica.

PMID- 15430342
TI  - Reticulosarcoma; eosinophilic granuloma.

PMID- 15430343
TI  - Eosinophilic granuloma of the skin.

PMID- 15430344
TI  - Lichen nitidus.

PMID- 15430345
TI  - Erythema induratum (Whitfield).

PMID- 15430346
TI  - Mycosis fungoides.

PMID- 15430347
TI  - Morphoea-like paraffinoma medicamentosa.

PMID- 15430348
TI  - Lupus erythematosus and rosaceous tuberculide.

PMID- 15430349
TI  - DISCUSSION of the chemical factors modifying radiotherapeutic response.

PMID- 15430350
TI  - The intensification of the fluorescent image in radiology.

PMID- 15430351
TI  - Cavernous angiomata.

PMID- 15430352
TI  - Stenosis of carpal tunnel compression of median nerve and flexor tendon sheaths
      combined with rheumatoid arthritis elsewhere.

PMID- 15430353
TI  - Arthrography of the shoulder-joint.

PMID- 15430354
TI  - DISCUSSION on treatment of achalasia of the cardia.

PMID- 15430355
TI  - DISCUSSION on hospital construction in the light of cross-infection.

PMID- 15430356
TI  - Endemic hepatitis among U.S. troops in post-war Germany.

PMID- 15430357
TI  - Uterine irritability as a cause of dyspareunia.

PMID- 15430358
TI  - DISCUSSION on resuscitation of the newborn.

PMID- 15430359
TI  - Streptomycin in urinary tuberculosis.

PMID- 15430360
TI  - The renal circulation.

PMID- 15430361
TI  - Two cases of sarcoidosis of the lungs with erythema nodosum.

PMID- 15430362
TI  - Arteriosclerosis; thrombosis of iliac arteries.

PMID- 15430363
TI  - Elephantiasis of left lower limb.

PMID- 15430364
TI  - Malignant mediastinal teratoma.

PMID- 15430365
TI  - Lymphosarcoma of cheek.

PMID- 15430366
TI  - Demonstration of honeycomb lungs.

PMID- 15430367
TI  - Wandering pulmonary infiltrations with eosinophilia.

PMID- 15430368
TI  - Free nipple transplant in breast reduction and breast amputation with special
      reference to surgical treatment in obesity.

PMID- 15430369
TI  - Exfoliative dermatitis with low plasma protein, oedema, fatty change in the liver
      and a filling defect in the stomach.

PMID- 15430370
TI  - Congenital bilateral accessory parotid gland hypertrophy; cervical sympathetic
      overactivity due to scar.

PMID- 15430371
TI  - Prerequisites of successful heparinization to prevent gangrene after frostbite.

PMID- 15430372
TI  - Determination of small quantities of nitrogen in serological precipitates and
      other biological materials.

PMID- 15430373
TI  - Hyperglycemic properties of crude pancreatic proteins.

PMID- 15430374
TI  - Stimulatory effect of aureomycin on the growth of chicks.

PMID- 15430375
TI  - Alveolar ventilation studies using the mass spectrometer.

PMID- 15430376
TI  - Cross transfusion; therapeutic effect in acute mercury nephrosis.

PMID- 15430377
TI  - Effect of celiac ganglionectomy and thoracolumbar sympathectomy or adrenal
      medullectomy on histamine ulcer in dogs.

PMID- 15430379
TI  - Expulsion-crescent: a new pathological red cell figure in human peripheral blood.

PMID- 15430378
TI  - Nutrition of animal cells in tissue culture; use of tweens in synthetic feeding
      mixtures.

PMID- 15430380
TI  - Accelerator-globulin and prothrombin preparation of accelerator-globulin free
      plasma.

PMID- 15430381
TI  - Relation of oxygen to photoreactivation of bacteria after ultraviolet radiation.

PMID- 15430382
TI  - Comparative action of aureomycin, chloromycetin, neomycin, Q-19, and polyxin B
      against gram negative bacilli.

PMID- 15430383
TI  - Content of desoxyribo and ribonucleic acids of retina under various conditions.

PMID- 15430384
TI  - Effect of adrenalectomy on spontaneous and induced proteinuria in the rat.

PMID- 15430385
TI  - The dermal loss of iron.

PMID- 15430386
TI  - Effect of DDT on testes and secondary sex characters of white leghorn cockerels.

PMID- 15430387
TI  - Synthesis of citrovorum factor from folic acid by liver slices; augmentation by
      ascorbic acid.

PMID- 15430389
TI  - Acute and subacute glomerulonephritis modified by adrenocorticotropin.

PMID- 15430388
TI  - Procaine and autonomic innervation.

PMID- 15430390
TI  - Metabolic changes associated with administration of adrenocorticotropin in the
      nephrotic syndrome.

PMID- 15430391
TI  - Effect of penicillin dosage schedule on treatment of experimental typhoid
      infections in mice.

PMID- 15430392
TI  - Prevention of loss of body fat by cortisone.

PMID- 15430393
TI  - Agglutination of cercariae of Schistosoma mansoni by immune sera.

PMID- 15430394
TI  - Practical application of a hemagglutination reaction in tuberculosis.

PMID- 15430395
TI  - Separation of pertussal toxin.

PMID- 15430396
TI  - Influence of feeding schedule on nitrogen utilization and excretion.

PMID- 15430397
TI  - Effect of adrenocorticotropic hormone and cortisone therapy on human plasma
      aminopeptidase activity.

PMID- 15430398
TI  - Application of the Feulgen reaction to the laboratory diagnosis of smallpox.

PMID- 15430399
TI  - Reversal of aminopterin inhibition in the chick embryo with desoxyribosides.

PMID- 15430400
TI  - Rapid production of atherosclerosis by administration of uranium in presence of
      hypercholesterolemia.

PMID- 15430401
TI  - Joint action of penicillin with chloramphenicol on an experimental streptococcal
      infection of mice.

PMID- 15430402
TI  - Resistance to epinephrine stress in the dog.

PMID- 15430403
TI  - Inhibition of vascularization of the rabbit cornea by local application of
      cortisone.

PMID- 15430404
TI  - Antihistamine therapy in experimental shock.

PMID- 15430405
TI  - Characterization and separation of an inhibitor of viral hemagglutination present
      in urine.

PMID- 15430406
TI  - A feathering syndrome in chicks after feeding optimal levels of lysine in absence
      of arginine.

PMID- 15430407
TI  - Determination of inulin by means of resorcinol.

PMID- 15430408
TI  - Acid-fast membranes of lipid pneumonia by fluorescence microscopy.

PMID- 15430409
TI  - Some biochemical aspects of herpes infection.

PMID- 15430410
TI  - Response of man to egg-adapted Colorado tick fever virus.

PMID- 15430411
TI  - Further studies on toxicity of thioacetamide in rats.

PMID- 15430412
TI  - Failure of malononitrile in therapy of experimental poliomyelitis.

PMID- 15430413
TI  - Cultivation of poliomyelitis virus (Lansing strain) in human embryonic and
      placental tissues.

PMID- 15430414
TI  - Distribution of azo-proteins in the tissues of the normal mouse.

PMID- 15430415
TI  - Development of reticulum cells and lymphocytes in transplants of rabbit lymph
      node to chick chorioallantois.

PMID- 15430416
TI  - Effect of cold, adrenocorticotropic and thyroid hormones on urinary excretion of
      pentose in the rat.

PMID- 15430417
TI  - Endogenous creatinine in serum and urine.

PMID- 15430418
TI  - Dicumarol labelled with C14.

PMID- 15430419
TI  - Relation of adrenal cortical steroids to antibody release.

PMID- 15430420
TI  - Methylandrostenediol: a non-virilizing derivative of testosterone in metastatic
      cancer of the breast.

PMID- 15430421
TI  - Alkaline phosphatase activity of human serum in cancer.

PMID- 15430422
TI  - Histamine as possible chemical mediator for cutaneous pain. Dual pain response to
      histamine.

PMID- 15430423
TI  - Use of ultraviolet light and fluorescent dyes in bacterial counting.

PMID- 15430424
TI  - Response of the pig to APF, B12, and B12b.

PMID- 15430425
TI  - Agglutination of mammalian erythrocytes by Newcastle disease virus.

PMID- 15430426
TI  - Effect of mercurials on kidney adenosine triphosphatase activity.

PMID- 15430427
TI  - Acetylcholine content of tyrode solution perfused through muscles as affected by
      calcium and procaine hydrochloride.

PMID- 15430428
TI  - "Spontaneous" ovulation in the rabbit following combined estrogen-progesterone
      treatment.

PMID- 15430429
TI  - Effect of cortisone on some reactions of hypersensitivity in laboratory animals.

PMID- 15430430
TI  - Daily administration of massive oral doses of thonzylamine hydro-chloride.

PMID- 15430431
TI  - Assay of methylcholanthrene-induced mammary tumors of mice for the mammary tumor
      milk agent.

PMID- 15430432
TI  - Experimental artificial left heart to permit surgical exposure of mitral valve in
      cats.

PMID- 15430433
TI  - Antigenic similarity of bovine strains of leptospirae (United States) and
      Leptospira pomona.

PMID- 15430434
TI  - Protective effect of para-aminopropiophenone against lethal doses of x-radiation.

PMID- 15430435
TI  - Effect of 4-amino-pteroylglutamic acid (aminopterin) on early pregnancy.

PMID- 15430436
TI  - Partial purification of viruses with an anion exchange resin.

PMID- 15430437
TI  - Anticonvulsant action of isopropyl alcohol.

PMID- 15430438
TI  - Therapy of paroxysmal pulmonary edema by anti-foaming agents.

PMID- 15430439
TI  - Determination of gastric acidity without intubation by use of cation exchange
      indicator compounds.

PMID- 15430440
TI  - Transmission and multiplication of Newcastle disease virus (nDV) in brains of
      suckling mice.

PMID- 15430441
TI  - Unique physico-chemical properties of Japanese B encephalitis virus
      hemagglutinin.

PMID- 15430442
TI  - A method for the determination of sodium ferrocyanide at low concentrations in
      body fluids.

PMID- 15430443
TI  - Sickle cell anemia, blood viscosity and sodium tetrathionate.

PMID- 15430444
TI  - Confirmation of presence of a gastric secretory depressant in gastric juice of
      humans.

PMID- 15430445
TI  - Amino acids of Bence-Jones protein.

PMID- 15430446
TI  - Changes in cell and plasma volumes produced by total body x radiation.

PMID- 15430447
TI  - Effect of ACTH on wound healing in humans.

PMID- 15430448
TI  - Symposium on respiratory obstruction in infancy and childhood: introduction.

PMID- 15430449
TI  - The diagnosis of obstructive lesions of the respiratory tract of children.

PMID- 15430450
TI  - Endobronchial foreign bodies.

PMID- 15430451
TI  - Vascular "rings" producing respiratory obstruction in infants.

PMID- 15430452
TI  - Branchial cyst as a cause of respiratory obstruction in infancy.

PMID- 15430453
TI  - Use of milk to control vomiting caused by aureomycin.

PMID- 15430454
TI  - The origin and evolution of diagnostic procedures with reference to diseases of
      the heart and circulation. V. Electrical registration of the activity of the
      heart.

PMID- 15430455
TI  - An introduction to the clinical applications of oximetry.

PMID- 15430456
TI  - A single scale absolute reading ear oximeter.

PMID- 15430457
TI  - A study of the oxygen saturation of arterial blood of normal newborn infants by
      means of a modified photo-electric oximeter: preliminary report.

PMID- 15430458
TI  - Measurement of blood content and arterial pressure in the human ear.

PMID- 15430459
TI  - Studies on circulation time with the aid of the oximeter.

PMID- 15430460
TI  - A plastic needle.

PMID- 15430461
TI  - Roentgenology in the diagnosis of tuberculosis.

PMID- 15430462
TI  - The tuberculin test.

PMID- 15430463
TI  - Histopathologic examination for tuberculosis.

PMID- 15430464
TI  - Bacteriologic examination for tuberculosis.

PMID- 15430465
TI  - The clinician's responsibility in the diagnosis of tuberculosis.

PMID- 15430466
TI  - A factor in neutralized human gastric juice which prolongs survival of
      gastrectomized rats.

PMID- 15430467
TI  - Clinical experiences with microwave diathermy.

PMID- 15430468
TI  - Extensive resection of the bowel for occlusion of the superior mesenteric artery:
      report of a case with postoperative studies of function of the gastrointestinal
      tract.

PMID- 15430469
TI  - Clinical observations on the use of cortisone in ophthalmic diseases: preliminary
      report.

PMID- 15430470
TI  - Failure of absorption of aureomycin and terramycin administered as a retention
      enema.

PMID- 15430471
TI  - Surgery of the femoral cutaneous nerves in the treatment of diseases of the hip:
      preliminary report.

PMID- 15430472
TI  - Psychiatric aspects of treatment of the painful phantom limb.

PMID- 15430473
TI  - [The corneo-labio-mandibular reflex].

PMID- 15430474
TI  - [Treatment of chronic epilepsy].

PMID- 15430475
TI  - [Electroshock and insulin in psychiatry].

PMID- 15430476
TI  - Behavioral concepts and psychotherapy.

PMID- 15430477
TI  - The Rorschach test and the questions of "prognosis" and "recovery" in syphilitic
      meningo-encephalitis.

PMID- 15430478
TI  - Educational therapy in a public mental hospital.

PMID- 15430479
TI  - Further studies on depersonalization.

PMID- 15430480
TI  - Chloral delirium.

PMID- 15430481
TI  - Psychological factors in shock therapy.

PMID- 15430482
TI  - A study of the mental status of schizophrenics hospitalized for over 25 years
      into their senium.

PMID- 15430483
TI  - Experiences in group psychotherapy with insulin-treated patients.

PMID- 15430484
TI  - A case of conjugal psychosis.

PMID- 15430485
TI  - The psychosis of association: folie a deux.

PMID- 15430486
TI  - The use of intravenous sodium amytal in psychiatric feeding problems.

PMID- 15430487
TI  - Psychodynamic modification of electric shock treatment.

PMID- 15430488
TI  - Psychiatric problems of the puerperium from the standpoint of prophylaxis.

PMID- 15430489
TI  - WALTER M. PAMPHILON, M. D., dies at 52.

PMID- 15430490
TI  - ADOLF MEYER, M. D., dies in Baltimore at 83.

PMID- 15430491
TI  - Time of decision.

PMID- 15430492
TI  - Quo vadis, psychiatry? Our profession at the crossroads.

PMID- 15430493
TI  - A low-cost psychoanalytic service; first year.

PMID- 15430494
TI  - Psychology of the hypnotist.

PMID- 15430495
TI  - A note on spontaneous hallucinations during hypnosis.

PMID- 15430496
TI  - A study of some psychological reactions during prepubescence to the idea of
      death.

PMID- 15430497
TI  - Brief shock therapy, and adjuvant to psychotherapy.

PMID- 15430498
TI  - The etiology of schizophrenia.

PMID- 15430499
TI  - Transference in psychotherapy.

PMID- 15430500
TI  - A Rorschach compendium, revised and enlarged.

PMID- 15430501
TI  - The place of action in personality change.

PMID- 15430502
TI  - The psychodynamic process of illness and recovery in a case of catatonic
      schizophrenia.

PMID- 15430503
TI  - Authority and liberty in the structure of Freud's thought.

PMID- 15430504
TI  - A psychotic personality in the South Seas.

PMID- 15430505
TI  - Frustration tolerance, frustration susceptibility, and overt disturbance.

PMID- 15430507
TI  - A pilot study of psychoanalytic practice in the United States, with suggestions
      for future studies.

PMID- 15430506
TI  - Group reading in mental hospitals.

PMID- 15430508
TI  - Patterns of parent-child relationships in schizophrenia.

PMID- 15430509
TI  - Mohave Indian autoerotic behavior.

PMID- 15430510
TI  - Three cases illustrative of emotional factors in dermatology: psoriasis,
      infectious eczematoid dermatitis, and chronic eczema of the hands.

PMID- 15430511
TI  - A case of paedophilia (legally rape) cured by psychoanalysis.

PMID- 15430512
TI  - The "discharging function" of electric shock and the anxiety problem.

PMID- 15430513
TI  - Regression tests for several samples.

PMID- 15430514
TI  - Test reliability and correction for attenuation.

PMID- 15430515
TI  - On the identifiability of Parameters in Thurstone's multiple factor analysis.

PMID- 15430516
TI  - Bias and error in multiple-choice tests.

PMID- 15430517
TI  - Connectivity and generalized cliques in sociometric group structure.

PMID- 15430518
TI  - On the effect of selection performed on some coordinates of a multi-dimensional
      population.

PMID- 15430519
TI  - Stress and the adrenal cortex with special reference to potassium metabolism.

PMID- 15430520
TI  - Adaptive reaction to stress.

PMID- 15430521
TI  - Anxiety, HCl secretion, and peptic ulcer etiology.

PMID- 15430522
TI  - The association of certain vegetative disturbances with various psychoses.

PMID- 15430523
TI  - The incidence of certain vegetative disturbances in relation to psychosis.

PMID- 15430524
TI  - Life situations, emotions, and Graves' disease.

PMID- 15430525
TI  - Psychocutaneous conditioning during the first two weeks of life.

PMID- 15430526
TI  - Tuberculosis and dependency; psychosomatic conference of the mental hygiene
      division of the university of Colorado Medical School, and the National Jewish
      Hospital, Denver.

PMID- 15430527
TI  - Life situations, emotions, and glaucoma.

PMID- 15430528
TI  - Measures of stress responsivity in younger and older men.

PMID- 15430529
TI  - Psychologic manifestations of the menstrual cycle.

PMID- 15430530
TI  - Psychotic factors in psychosomatic illness.

PMID- 15430531
TI  - The effect of low oxygen on psychologic performance tests in psychoneurotic
      patients and normal controls.

PMID- 15430532
TI  - Dermatologic hypochondriasis; a form of schizophrenia.

PMID- 15430533
TI  - Recurrent herpes simplex; a psychiatric and laboratory study.

PMID- 15430534
TI  - Psychic stimulation of prostatic secretion.

PMID- 15430535
TI  - The care of the patient with cancer.

PMID- 15430536
TI  - The public health nurse in a cancer control project.

PMID- 15430537
TI  - Human needs and nursing.

PMID- 15430538
TI  - Can it be forty years?

PMID- 15430539
TI  - Diagnosis tuberculosis; the nurse helps the patient face tuberculosis.

PMID- 15430540
TI  - The tuberculous patient at home.

PMID- 15430541
TI  - The new mother comes home.

PMID- 15430543
TI  - The story of the new NOPHN cost analysis method.

PMID- 15430542
TI  - Summer care of infants.

PMID- 15430544
TI  - Changing maternity service in a changing world.

PMID- 15430545
TI  - Changing maternity and newborn care in the hospital.

PMID- 15430546
TI  - A big city and polio.

PMID- 15430547
TI  - Public health nursing, background for variety.

PMID- 15430548
TI  - Inter-agency teamwork for tuberculosis control.

PMID- 15430549
TI  - A nurse looks at mass chest x-ray surveys.

PMID- 15430550
TI  - [Endovenous anesthesia with methylallylisopropylbarbituric acid in obstetrics and
      gynecology].

PMID- 15430551
TI  - [Anatomo-histopathogenetic observations on red myoma of the uterus].

PMID- 15430552
TI  - [Trichomonas vaginitis].

PMID- 15430553
TI  - [Physiopathology of the puerperium].

PMID- 15430554
TI  - [Is there an interfunctional relation between the spleen and ovaries in
      puberty?].

PMID- 15430555
TI  - [Cholinesterase in obstetrics].

PMID- 15430556
TI  - [Cancer of the uterus and the synthesizing power of the liver; the resorcin
      test].

PMID- 15430557
TI  - [Trichloroethylene in general anesthesia and as an auto-analgesic in obstetrics].

PMID- 15430558
TI  - [Use of ultrasonics in gynecology].

PMID- 15430559
TI  - Speciation in ancient lakes.

PMID- 15430560
TI  - Perspectives in the field of morphogenesis.

PMID- 15430561
TI  - The practical nurse goes to college.

PMID- 15430562
TI  - Your community needs you.

PMID- 15430563
TI  - Forever ugh.

PMID- 15430564
TI  - WHERE the U.S. Government has failed.

PMID- 15430565
TI  - SNEEZING season.

PMID- 15430566
TI  - DRUG digest.

PMID- 15430567
TI  - No longer fashion's guinea pig.

PMID- 15430568
TI  - Candid comments--a long road turning.

PMID- 15430569
TI  - R.N. reports: on the 1950 House of Delegates' sessions.

PMID- 15430570
TI  - R.N. in the sportlight.

PMID- 15430571
TI  - Education for leadership.

PMID- 15430573
TI  - MALARIA.

PMID- 15430572
TI  - In conquest of malaria.

PMID- 15430574
TI  - Office nurse.

PMID- 15430575
TI  - Patients, patience and provocations.

PMID- 15430576
TI  - The radiography of the biliary tract.

PMID- 15430577
TI  - An intra-cavity technique for carcinoma of the cervix.

PMID- 15430578
TI  - Radiography in a chest clinic.

PMID- 15430579
TI  - Light-weight plastic film holders for cardioangiography.

PMID- 15430581
TI  - Thoughts in radiography.

PMID- 15430580
TI  - The roentgen museum.

PMID- 15430582
TI  - Foetal frolics.

PMID- 15430583
TI  - Thoughts on an African x-ray department.

PMID- 15430584
TI  - Radiography at sea.

PMID- 15430585
TI  - Aid to radiography of intervertebral spaces of the lumbar spine.

PMID- 15430586
TI  - Radiography in Kuala Lumpur.

PMID- 15430588
TI  - SYMPOSIUM on cancer of the cervix uteri.

PMID- 15430587
TI  - Radiotherapy in the south of France.

PMID- 15430589
TI  - Symposium on cancer of the cervix uteri: introduction.

PMID- 15430590
TI  - Diagnosis of cancer of the cervix: the early lesion.

PMID- 15430591
TI  - The dispersion of cancer of the cervix.

PMID- 15430592
TI  - The classification of cervical cancer.

PMID- 15430593
TI  - The surgical treatment of cancer of the cervix.

PMID- 15430594
TI  - Radium treatment of carcinoma of the cervix uteri.

PMID- 15430595
TI  - Roentgen treatment of cancer of the cervix.

PMID- 15430596
TI  - Angiocardiography in congenital heart disease of cyanotic type. II. Observations
      on tricuspid stenosis or atresia with hypoplasia of the right ventricle.

PMID- 15430597
TI  - A simple serialographic technic for cerebral angiography.

PMID- 15430598
TI  - The use of gastric mucin as a barium suspension medium; a preliminary report.

PMID- 15430599
TI  - Use of micropulverized barium sulfate in x-ray diagnosis; a preliminary report.

PMID- 15430600
TI  - [Cerebral tumor and papilledema].

PMID- 15430601
TI  - [Colloidal lability of the serum of subjects with gastroduodenal ulcers;
      refractometric research].

PMID- 15430602
TI  - [Behavior of liver function in p-aminosalicylic acid therapy].

PMID- 15430603
TI  - [Case of hemochromatosis with familial characteristics].

PMID- 15430604
TI  - [Laparotomy in Equidae].

PMID- 15430605
TI  - [Gaseous indigestion of the rumen of bovines].

PMID- 15430606
TI  - [Vegetative endocarditis due to Pasteurella in a pig].

PMID- 15430607
TI  - [Tuberculosis in a goose].

PMID- 15430608
TI  - [Treatment of pasteurellosis of the rabbit by antagonist complexes based on
      streptomycin].

PMID- 15430609
TI  - [Obstetric notes].

PMID- 15430610
TI  - [Periarteritis nodosa in a cow].

PMID- 15430611
TI  - [Treatment by exchange transfusion or simple transfusion of the newborn mule with
      hemolytic jaundice due to maternal immunization].

PMID- 15430612
TI  - [Iso-agglutination groups in the horse].

PMID- 15430613
TI  - [Results of the entrance examinations to the national veterinary schools in
      1949].

PMID- 15430614
TI  - [Hereditary hernias of domestic animals].

PMID- 15430616
TI  - [Sterility in the cow].

PMID- 15430615
TI  - [Equine piroplasmosis in Gironde].

PMID- 15430617
TI  - [Sanitary control of bulls used for artificial insemination].

PMID- 15430618
TI  - [Splenomegaly and hemorrhagic accidents in the sow].

PMID- 15430619
TI  - [New aspects of infection of Equidae by Salmonella abortus equi].

PMID- 15430620
TI  - [The problem of phenothiazine].

PMID- 15430621
TI  - [Treatment of newborn calf disease by toad venom].

PMID- 15430622
TI  - [Localization and frequency of Cysticercus bovis in meat inspection in the
      departement of La Vendee].

PMID- 15430624
TI  - [Friez' obstetrical sling: its use].

PMID- 15430623
TI  - [Precocious gestation].

PMID- 15430625
TI  - Commentary: mathematics in the larger context.

PMID- 15430626
TI  - Conduction electrons in non-metallic solids.

PMID- 15430627
TI  - Activation processes in the sensitiveness of explosives.

PMID- 15430628
TI  - Experimental design.

PMID- 15430629
TI  - Artificial lactation and perfusion of the bovine mammary gland.

PMID- 15430630
TI  - Rowett Research Institute.

PMID- 15430631
TI  - Crystal chemical considerations of the surface chemistry of Silica.

PMID- 15430632
TI  - Influence of interfacial potential on friction and surface damage.

PMID- 15430633
TI  - Nucleic acids: relationship between ribo- and deoxyribonucleases.

PMID- 15430634
TI  - New formulae for double refraction in liquids.

PMID- 15430635
TI  - Shift of the Aromatic band in substituted benzene.

PMID- 15430636
TI  - Reaction of chlorine cations with olefins.

PMID- 15430637
TI  - Mechanism of the Weissenberg effect.

PMID- 15430638
TI  - Improved method for precipitation of polymers from solution.

PMID- 15430639
TI  - An appraisal of current methods for the treatment of portal hypertension.

PMID- 15430640
TI  - The effect of resection of the sympathetic and parasympathetic innervation of the
      stomach upon gastric acidity.

PMID- 15430642
TI  - Ulcerative colitis.

PMID- 15430641
TI  - Cancer of the large bowel-operative considerations.

PMID- 15430643
TI  - Facts and problems of hepatitis.

PMID- 15430644
TI  - Blood test for cancer.

PMID- 15430645
TI  - Corticodiencephalic gastrointestinal syndromes in epileptics.

PMID- 15430646
TI  - A vacuum furnace for use in the temperature range 1000-2000 degree C.

PMID- 15430647
TI  - A high intensity ultraviolet continuum source for use in spectrophotometry.

PMID- 15430648
TI  - A rotary McLeod gauge.

PMID- 15430649
TI  - A multiple Kerr-cell camera.

PMID- 15430650
TI  - A method of measuring spurious counts in Geiger-Muller counters.

PMID- 15430651
TI  - The measurement of the magnetic field in a nuclear spectrometer.

PMID- 15430652
TI  - Tests of flowing junction diffusion cells with interference methods.

PMID- 15430653
TI  - Balloon-borne instrumentation for neutron detection.

PMID- 15430654
TI  - Nuclear emulsions and the measurement of low energy neutron spectra.

PMID- 15430655
TI  - A high resolution beta-ray spectrometer.

PMID- 15430656
TI  - The velocity of propagation of the discharge in Geiger-Muller counters.

PMID- 15430657
TI  - End and wall corrections for absolute beta-counting in gas counters.

PMID- 15430658
TI  - Scintillation type alpha-particle detector.

PMID- 15430659
TI  - The theory and properties of low voltage radiation counters.

PMID- 15430660
TI  - A useful fast coincidence circuit.

PMID- 15430661
TI  - An effective vacuum cut-off.

PMID- 15430662
TI  - A remote-control method of opening ampoules of active materials.

PMID- 15430663
TI  - Regulated low voltage power supply.

PMID- 15430664
TI  - Extension of the low pressure range of the ionization gauge.

PMID- 15430665
TI  - A circumferential recording microphotometer.

PMID- 15430666
TI  - Water-proofing rocksalt for infra-red absorption cells.

PMID- 15430667
TI  - An improved electrode cutter for spectrographic laboratories.

PMID- 15430668
TI  - Pulsed air core series disk generator for production of high magnetic fields.

PMID- 15430669
TI  - ELECTRON microscope.

PMID- 15430670
TI  - MINI-CHOPPER.

PMID- 15430671
TI  - "PRINTED-circuit" TV tuner.

PMID- 15430672
TI  - SUBMINIATURE electrometer type CK5889.

PMID- 15430673
TI  - THREE-stage non-magnetic mass spectrometer.

PMID- 15430675
TI  - TEMPERATURE control.

PMID- 15430674
TI  - ELECTROSTATIC generator.

PMID- 15430676
TI  - DIODE modulator for video frequencies.

PMID- 15430677
TI  - ULTRA-sensitive D.C. current measuring device.

PMID- 15430678
TI  - MICRO-manometer.

PMID- 15430679
TI  - A transfer device for low boiling liquids.

PMID- 15430680
TI  - A sector-type doublefocusing magnetic spectrometer.

PMID- 15430681
TI  - A linear preamplifier for driving a long coaxial cable.

PMID- 15430682
TI  - A new vacuum gauge.

PMID- 15430683
TI  - A 4 pi-radiometer.

PMID- 15430684
TI  - A recording torque magnetometer.

PMID- 15430685
TI  - Molecular diffraction attachment for RCA microscope.

PMID- 15430686
TI  - Apparatus for rapid measurement of internal friction.

PMID- 15430688
TI  - Microwave power stabilizer.

PMID- 15430687
TI  - Observations on some properties of ultra-high frequency gas discharges.

PMID- 15430689
TI  - A recording fluxmeter of high accuracy and sensitivity.

PMID- 15430690
TI  - Simple variable space infrared absorption cell.

PMID- 15430691
TI  - Duration of scintillations from organic phosphors.

PMID- 15430692
TI  - Instrument for directional studies of cosmicray intensity.

PMID- 15430693
TI  - Measurement of secondary electron emission from dielectric surfaces.

PMID- 15430694
TI  - A high speed expansion value for cloud-chamber control.

PMID- 15430695
TI  - Single element verniers reading two or three dimensions.

PMID- 15430696
TI  - Coincidence circuit for a scintillation detector of radiation.

PMID- 15430697
TI  - A 100,000,000-frame-per-second camera.

PMID- 15430698
TI  - Energy dependence of the naphthalene scintillation detector.

PMID- 15430699
TI  - Modification of electron microscope for electron optical shadow method.

PMID- 15430700
TI  - Microtome knife sharpness.

PMID- 15430701
TI  - Glass variable microleaks for gases.

PMID- 15430702
TI  - Ultra-high vacuum ionizatior manometer.

PMID- 15430703
TI  - An all-metal ionization gauge.

PMID- 15430704
TI  - A convenient leak for testing helium leak detectors.

PMID- 15430705
TI  - Preparation of unbacked metallic film.

PMID- 15430706
TI  - Comments on "Velocity acceleration response from a seismic pick-up via controlled
      damping".

PMID- 15430707
TI  - [One-stage gastroduodenopancreatectomy].

PMID- 15430708
TI  - [Pathogenic bases for the use of antibiotics and chemotherapeutics (PAS) as aids
      in the surgical therapy of tuberculosis localized in the genitourinary tract].

PMID- 15430710
TI  - [The pathogenesis of ascites].

PMID- 15430709
TI  - [Treatment of cancer of the prostate].

PMID- 15430711
TI  - [An eczema patch and its mysteries].

PMID- 15430712
TI  - [Onanism, a biblical theme; coitus interruptus].

PMID- 15430713
TI  - [Allergic diseases of industrial origin].

PMID- 15430714
TI  - [Physical allergy].

PMID- 15430715
TI  - [Acute gonococcic peritonitis in the right upper quadrant in women; Fitzhugh
      syndrome].

PMID- 15430716
TI  - [Erythrocyte and leukocyte count and the determination of hematocrit, hemoglobin
      and mean corpuscle volume in 893 infants and children from the first week of life
      to 7 years].

PMID- 15430717
TI  - [Gastroduodenal ulcer in children].

PMID- 15430718
TI  - [Paroxysmal tachycardia in an infant].

PMID- 15430719
TI  - [Blood transfusion, its indications].

PMID- 15430720
TI  - [Development of BCG vaccination in the Unidad sanitaria of Quinta Normal].

PMID- 15430721
TI  - [Clinical aspects of BCG vaccination].

PMID- 15430722
TI  - [Collagen diseases].

PMID- 15430723
TI  - [Studied on goiter. VII. Structural characteristics of experimental endemic
      goiter].

PMID- 15430724
TI  - [Electrocardiographic exploration of the posterior surface of the heart. I.
      Normal morphology of the esophageal and dorsal tracings and their variations
      according to the position of the heart in space].

PMID- 15430725
TI  - [Weltmann reaction in syphilis].

PMID- 15430726
TI  - [Tuberculous intestinal perforations].

PMID- 15430727
TI  - [Determination of calcium and magnesium].

PMID- 15430728
TI  - [Osteogenesis imperfecta; a viable newborn with Vrolik syndrome].

PMID- 15430729
TI  - [Rectosigmoid polypi].

PMID- 15430731
TI  - [Vitamin B12].

PMID- 15430730
TI  - [Renal cystadenoma].

PMID- 15430732
TI  - [Absenteeism in industry due to grippe].

PMID- 15430733
TI  - [Report on the treatment of leprosy].

PMID- 15430734
TI  - [Barlow's disease in Bogota].

PMID- 15430735
TI  - [Biotypological and orthogenetic study of a group of children from the
      Beneficencia de Cundinamarca].

PMID- 15430736
TI  - [New treatment of vertigo].

PMID- 15430737
TI  - [Vaginal lacerations during labor].

PMID- 15430738
TI  - [Physiopathology of uterine contraction; labor in a case of multiple sclerosis].

PMID- 15430739
TI  - [Vascular factor in functional dysmenorrhea].

PMID- 15430740
TI  - [Vestibular anal anomaly].

PMID- 15430741
TI  - [Failure of sterilization according to Madlener].

PMID- 15430742
TI  - [Retention of placenta in a case of induced labor].

PMID- 15430743
TI  - [Gonadotropin test in the functional diagnosis of amenorrhea].

PMID- 15430744
TI  - [New method for the prenatal diagnosis of sex].

PMID- 15430745
TI  - [Perforating mole].

PMID- 15430746
TI  - [Considerations on a case of hydrocephalus].

PMID- 15430747
TI  - [Hemolytic transfusion reaction due to anti-M sensitization].

PMID- 15430748
TI  - [Simple method of registering the agglutination of erythrocytes "in vitro"].

PMID- 15430749
TI  - [A constitutional hemorrhagic disease characterized by isolated prolongation of
      the bleeding time (Willebrand's disease; study of 9 cases)].

PMID- 15430750
TI  - [Willebrand's disease (constitutional thrombopathy or pseudohemophilia)].

PMID- 15430751
TI  - [Leukogenic power of eosin in ingestion].

PMID- 15430752
TI  - [Photometric study of the thrombin-fibrinogen reaction].

PMID- 15430753
TI  - [Early diagnosis of sarcoma of the lymphoid organs].

PMID- 15430754
TI  - [Rapid panoptic staining of hematological preparations].

PMID- 15430755
TI  - [The role of the suprarenal cortex in leukopoiesis and in immunity; cytologic
      modifications of the blood, of the spleen and of the thymus, after injection of
      suprarenal cortex extract].

PMID- 15430756
TI  - [The role of the suprarenal cortex in leukopoiesis and in immunity; modifications
      of blood proteins and antibodies after injection of suprarenal cortex extract in
      the rat].

PMID- 15430757
TI  - [Heparin tolerance test in vitro; hypocoagulability test, its application in
      diagnosis of hemorrhagic syndromes; hypercoagulability test, its application in
      the diagnosis of thrombosis].

PMID- 15430758
TI  - [Prothrombin time in the presence of a heterologous thromboplastin].

PMID- 15430759
TI  - [Critical study of the remissions in the course of acute leukemia treated by
      exchange transfusions (comparison with spontaneous remissions and those induced
      by folic acid antagonists)].

PMID- 15430760
TI  - [The structure of erythrocytes].

PMID- 15430761
TI  - [Research on the means of preventing and treating thrombosis; the question of
      thrombocytopenia].

PMID- 15430762
TI  - [Goiter and thyroid pathology in Belgium; thyroid and other endocrine glands].

PMID- 15430763
TI  - [Silicosis in the metallurgic industry].

PMID- 15430764
TI  - [Renal tumor treated by thoraco-phreno-laparatomy].

PMID- 15430765
TI  - [Occipital response to electric stimulation in man].

PMID- 15430766
TI  - [Ministry of Health report on epidemics, 16-29 April, 1950].

PMID- 15430767
TI  - [Goiter and thyroid pathology in Belgium; treatment of thyrotoxicosis].

PMID- 15430768
TI  - [Bone tomography, especially of the vertebral column].

PMID- 15430769
TI  - [Symptomatology and treatment of varicose veins].

PMID- 15430770
TI  - [Synthetic antithyroid substances in treatment of Basedow's disease].

PMID- 15430771
TI  - [Professional diseases of nurses; palpebral eczema caused by streptomycin].

PMID- 15430772
TI  - [Treatment of cancer with artificial radioactive elements].

PMID- 15430773
TI  - [Rapid death in abortion and Selye's syndrome of adaptation].

PMID- 15430774
TI  - [History of St-Bartholomew's Hospital].

PMID- 15430775
TI  - [Goiter and thyroid pathology in Belgium; a new case of Basedow's disease treated
      with radioactive iodine].

PMID- 15430776
TI  - [Lung pathology; synthesis of actual conceptions of classical and recently
      discovered lung diseases].

PMID- 15430777
TI  - [Medical treatment of renal lithiasis].

PMID- 15430778
TI  - [Epidemiologic data, May 28-June 10, 1950].

PMID- 15430779
TI  - [Advances and setbacks in medicine].

PMID- 15430780
TI  - [Vegetative centers of the cerebral cortex].

PMID- 15430781
TI  - [Arthropathic form of syringomyelia].

PMID- 15430782
TI  - [Esophago-pleural fistula in an intrapleural left pneumothorax; therapy by
      thoracoplasty and muscle plastic surgery].

PMID- 15430783
TI  - [Meig's syndrome].

PMID- 15430784
TI  - [Larval pulmonary abscess].

PMID- 15430785
TI  - [3 cases of cardiac insufficiency due to escaping carbon monoxide from blast
      furnaces].

PMID- 15430786
TI  - [Rapid treatment of oil dermatitis].

PMID- 15430787
TI  - [Treatment of pain in amputation stumps].

PMID- 15430788
TI  - [Centennial of Internet des Hopitaux de Nancy].

PMID- 15430789
TI  - [Diagnosis of a mediastinal tumor; hernia of a cyst of the liver through the
      diaphragm].

PMID- 15430790
TI  - [Diagnosis of tularemia by biologic methods].

PMID- 15430791
TI  - [Separate examination of the lungs by bronchospirometry; critical study of 80
      examinations].

PMID- 15430792
TI  - [Amyotrophic form of Friedreich's disease; do intermediate forms exist between
      Friedreich's disease and Charcot-Marie disease?].

PMID- 15430793
TI  - [Pancoast-Tobias syndrome due to a fibrosarcoma of pleural origin].

PMID- 15430795
TI  - [Therapeutic use of low frequency electric currents called diadynamic currents].

PMID- 15430794
TI  - [Adoption].

PMID- 15430796
TI  - [Dental caries].

PMID- 15430797
TI  - [Treatment of tuberculosis with para-amino-salicylic acid].

PMID- 15430798
TI  - [Are large intravenous injections of glucose in hypertonic solution harmful to
      the kidney?].

PMID- 15430799
TI  - [Not Available].

PMID- 15430800
TI  - [Treatment of hypertension with chlorinergic medication].

PMID- 15430801
TI  - [Fundamental mechanism of the inflammatory processes].

PMID- 15430802
TI  - [Surgical treatment of recent venous thrombosis].

PMID- 15430803
TI  - [Transmission of pathogenic organisms to man by milk and dairy products].

PMID- 15430804
TI  - [Primary tumors of the bronchi].

PMID- 15430805
TI  - [Dysproteinemic plasmocytic interstitial nephritis].

PMID- 15430806
TI  - [Acute benign pulmonary syndromes].

PMID- 15430807
TI  - [Proctalgia fugax].

PMID- 15430808
TI  - [Two cases of Wolff-Parkinson-White syndrome of rheumatic etiology].

PMID- 15430809
TI  - [Sex glands and the skeleton].

PMID- 15430810
TI  - [Surgical operation on paradental tumor].

PMID- 15430811
TI  - [A contribution to the study of dentine graft. Introducing a new instrument].

PMID- 15430812
TI  - [Continuous forces in the treatment of fractures of jaws ossified in
      malposition].

PMID- 15430813
TI  - [Birth absence of thyroid and its effects on the dental system].

PMID- 15430814
TI  - [Essay on ethiology and pathogenic classification of facial algiae].

PMID- 15430815
TI  - [Impacted lower third molar in sigmoidal position].

PMID- 15430816
TI  - [Medical treatment of tuberculous cervical mono- and polyadenitis].

PMID- 15430817
TI  - [Stress breaker for extension saddle].

PMID- 15430818
TI  - [Biology and technic in full denture].

PMID- 15430819
TI  - [Histopathological survey of the development and evolution of an incipient
      carcinoma under a plate].

PMID- 15430820
TI  - [Temporal lobe in oto-neuro-ophthalmology].

PMID- 15430821
TI  - [Anatomy of the temporal lobe].

PMID- 15430822
TI  - [Physiology of the temporal lobe].

PMID- 15430823
TI  - [Neuro-psychic semeiology of temporal injuries].

PMID- 15430824
TI  - [The temporal lobe in oto-neuro-ophthalmology; neuro-psychic symptomatology].

PMID- 15430825
TI  - [The temporal lobe in oto-neuro-ophthalmology; ophthalmologic symptomatology].

PMID- 15430826
TI  - [The temporal lobe in oto-neuro-ophthalmology; cochleovestibular symptomatology].

PMID- 15430827
TI  - [Temporal lobe; radiological study].

PMID- 15430828
TI  - [Electro-encephalographic study of the temporal lobe].

PMID- 15430829
TI  - [Electroencephalographic study of the temporal lobe].

PMID- 15430830
TI  - [Etiologico-clinical classifications of diseases of the temporal lobe;
      introduction].

PMID- 15430831
TI  - [Tumors of the temporal lobe].

PMID- 15430832
TI  - [Abscesses of the temporal lobe].

PMID- 15430833
TI  - [Encephalitis, encephalosis, encephalopathy of the temporal lobe].

PMID- 15430834
TI  - [Vascular lesions of the temporal lobe].

PMID- 15430835
TI  - [Traumatism of the temporal lobe].

PMID- 15430836
TI  - [Surgery of lesions of the temporal lobe].

PMID- 15430838
TI  - [Medical treatment of diseases of the temporal lobe].

PMID- 15430837
TI  - [Treatment of abscesses of the temporal lobe].

PMID- 15430839
TI  - [Prevention of brucellosis; present state of the question in human and veterinary
      medicine].

PMID- 15430840
TI  - [Relations between outbreaks of crime in Ankara and the different seasons of the
      year; role of atmospheric electricity in these relations].

PMID- 15430841
TI  - [Primary tumors of the bone marrow in domestic mammals].

PMID- 15430842
TI  - [Mortality in France in 1943].

PMID- 15430843
TI  - [Bicentennial of the principle of least action].

PMID- 15430844
TI  - [Medieval research inspired by the Near East].

PMID- 15430845
TI  - [Methods of immunization in ultravirus diseases of animals].

PMID- 15430846
TI  - [Phenomena of resistance to infection and of immunity in virus diseases of
      plants].

PMID- 15430847
TI  - [Effect of radon on uterine contraction].

PMID- 15430848
TI  - [Persistent non-exudative ulcerous keratitis and corresponding dental
      abnormality].

PMID- 15430849
TI  - [Prevention of accidents due to large doses of vitamin D by addition of vitamin
      A; experimental contribution].

PMID- 15430850
TI  - [The danger of putrefying carcasses in fodder].

PMID- 15430851
TI  - [Therapeutic use of acid magnesium iodoiodide].

PMID- 15430852
TI  - [Pituitary tumor and hypersomnia].

PMID- 15430853
TI  - [Role of allergy and immunity in the development of tuberculosis].

PMID- 15430854
TI  - [Therapeutic pneumoperitoneum; physiopathological considerations and place in the
      treatment of pulmonary tuberculosis].

PMID- 15430855
TI  - [Extrapleural pneumothorax].

PMID- 15430856
TI  - [Endocavitary streptomycin].

PMID- 15430857
TI  - [Anatomical cure by bilateral collapsotherapy: thoracoplasty on the left,
      pneumothorax on the right].

PMID- 15430859
TI  - [Error in administering BCG serum].

PMID- 15430858
TI  - [Physiopathology of cavitary distensions].

PMID- 15430860
TI  - [Importance of the association of antibiotics in the treatment of pulmonary
      tuberculosis].

PMID- 15430861
TI  - [Sudden death due to rupture of a lymph node in the trachea in the course of a
      primary infection; anatomic findings].

PMID- 15430862
TI  - [Temporary abatement and efficacious resumption after streptomycin of certain
      dangerous pneumothoraxes].

PMID- 15430863
TI  - [Thrombophlebitis following pneumolysis during pre- and postoperative
      streptomycin therapy; cavitary insufflation followed by perforation treated by
      pleurotomy, antibiotics and PAS].

PMID- 15430864
TI  - [Current medico-social aspect of pulmonary tuberculosis and systematic
      examination; practical conclusions].

PMID- 15430866
TI  - [The future of pleurotomies for tuberculous pyothorax].

PMID- 15430865
TI  - [Extrapleural pneumothorax voluntarily detained from the start].

PMID- 15430867
TI  - [Rapid determination of streptomycin resistance].

PMID- 15430868
TI  - [Importance of intravenous administration in the treatment of chronic pulmonary
      tuberculosis by PAS].

PMID- 15430869
TI  - [Radiological images of pulmonary condensation and of asymptomatic mediastinal
      adenopathy in two children vaccinated at birth with BCG].

PMID- 15430870
TI  - [Reflex intestinal occlusion following endoscopic detachment of the mediastinum].

PMID- 15430871
TI  - [Therapeutic pneumoperitoneum; clinical results of 111 cases].

PMID- 15430872
TI  - [Pulmonary tuberculosis detected by systematic examination; study of 187 cases
      treated in the Belligneux Sanatorium].

PMID- 15430873
TI  - The place of orthopaedic surgery in the treatment of chronic rheumatic conditions
      of the hip and knee joints.

PMID- 15430874
TI  - Vitamin E in rheumatism and arthritis.

PMID- 15430875
TI  - The upper trapezii in the study of certain rheumatic disorders.

PMID- 15430876
TI  - Initial symptoms in spondylarthritis ankylopoietica.

PMID- 15430877
TI  - Studies on the pathogenesis of rheumatoid arthritis; clinical observations during
      and after a course of insulin and simultaneous administration of glucose and
      glucose metabolites to patients with rheumatoid arthritis.

PMID- 15430878
TI  - Rheumatism in relation to chronic genito-urinary infection.

PMID- 15430879
TI  - [Symptoms and complications of the nervous system in murine typhus].

PMID- 15430880
TI  - [A new metabolic test: the thyroxin test].

PMID- 15430881
TI  - [Serum cholinesterase and protidemia].

PMID- 15430882
TI  - [Case of brucellosis treated with aureomycin].

PMID- 15430883
TI  - [Transorbital lobotomy in intolerable pain].

PMID- 15430884
TI  - [Clinical aspects and operative technic of congenital absence of the vagina].

PMID- 15430885
TI  - [Anhemolytic prehepatic jaundice; casuistic and pathogenetic contribution].

PMID- 15430886
TI  - [A gonococcic peritoneal syndrome].

PMID- 15430887
TI  - [Endobronchial administration of antibiotics in the treatment of pulmonary
      abscess].

PMID- 15430888
TI  - [Bronchiectatic bronchiolitis].

PMID- 15430889
TI  - [Casuistic contribution and clinicopathogenetic findings in elliptopoikilocytic
      erythropathy, Rietti-Greppi-Micheli type].

PMID- 15430890
TI  - [Two cases of hypospadias treated by the Chocholka method].

PMID- 15430892
TI  - [Steroids and tumors].

PMID- 15430891
TI  - [Marie's hypertrophic osteoarthropathy and neoplasms of the lung].

PMID- 15430893
TI  - [Conservative treatment of perforated gastric ulcers].

PMID- 15430894
TI  - [Influence of hereditary hypertensive factors on the evolution of diffuse
      glomerular nephritis].

PMID- 15430895
TI  - [Casuistic contribution and clinicopathogenetic findings on elliptopoikilocytic
      erythropathy, Rietti-Greppi-Micheli type].

PMID- 15430896
TI  - [Use of synthetic anti-histamines in various diseases].

PMID- 15430897
TI  - [Clinical aspects of cancer of the penis].

PMID- 15430899
TI  - [Standardization of dental symbols].

PMID- 15430898
TI  - [Chemistry of dentin; magnesium in dentin].

PMID- 15430900
TI  - [2 cases of severe odontogenic infection].

PMID- 15430901
TI  - [Metastatic pulmonary abscess of dental origin].

PMID- 15430902
TI  - [Bite raising in dental prosthesis].

PMID- 15430903
TI  - [Special technic in construction of prostheses with indirect isodromia].

PMID- 15430904
TI  - [Hinge axis, MacCollum method].

PMID- 15430905
TI  - [Biological management in orthodontics; from local limitation to constitutional
      limitation in dento-facial orthopedic treatment].

PMID- 15430906
TI  - [Ozone therapy in stomatological practice].

PMID- 15430907
TI  - [New articulated guide for the reduction of mandibular stumps].

PMID- 15430908
TI  - [Meniere's vertigo (angioneurotic crisis of the 8th nerve) caused by a dental
      granuloma].

PMID- 15430909
TI  - [Reimplantation of teeth].

PMID- 15430910
TI  - [Biological management in orthodontic treatment; from local limitation to
      constitutional limitation in orthopedic dento-facial therapy].

PMID- 15430911
TI  - Reduction and disappearance of anopheline species prevailing in Attica (Greece)
      as a result of control program carried out during 1946-1949.

PMID- 15430912
TI  - [Observations on the characteristics of endemic malaria in southwestern Sicily].

PMID- 15430913
TI  - [Eight old registers of therapeutic prescriptions and the use of cinchona in Rome
      in the past].

PMID- 15430914
TI  - Presidential address.

PMID- 15430915
TI  - Rheumatic fever in school children in Utah.

PMID- 15430916
TI  - Use of radon ointment in the treatment of post-irradiation ulcers.

PMID- 15430917
TI  - Electroencephalography in clinical medicine.

PMID- 15430918
TI  - Lives of great men all remind us.

PMID- 15430920
TI  - Advances in research on poliomyelitis.

PMID- 15430919
TI  - Adenomatosis; a case report.

PMID- 15430921
TI  - Alcoholism and the public.

PMID- 15430922
TI  - The National Health Service of Great Britain.

PMID- 15430923
TI  - Stricture of the urethra.

PMID- 15430924
TI  - Management and treatment of incipient tuberculosis.

PMID- 15430925
TI  - "Effort" thrombosis of the axillary vein.

PMID- 15430926
TI  - Ventricular paroxysmal tachycardia; 2 unusual cases.

PMID- 15430927
TI  - The action of mitotic poisons on normal and pathological blood-cell formation.

PMID- 15430928
TI  - The curative properties of nitrogen mustard (nitrogranulogen) in inflammatory
      diseases.

PMID- 15430929
TI  - [Clinical and experimental research on nitrogen mustard].

PMID- 15430930
TI  - Action of nitrogen mustard, potassium arsenite, and urethane on living cells in
      vitro.

PMID- 15430931
TI  - [Histomorphology of leukemic changes of reticular origin].

PMID- 15430932
TI  - An antagonistic effect of p-aminobenzoic acid and sulfapyridine on the leukocyte
      count in leukemia.

PMID- 15430933
TI  - [Treatment of hemoblastosis with cytostatic substances].

PMID- 15430934
TI  - [Effect of choline, pyridoxine, etc., on granulocytopenia due to cytostatic
      substances].

PMID- 15430935
TI  - [Acute leukemia and folic acid antagonists].

PMID- 15430936
TI  - The histamine of leukoemic granulocytes.

PMID- 15430937
TI  - New criteria for the evaluation of the bone-marrow cells mitotic activity.

PMID- 15430938
TI  - [Effect of a mitotic poison on tissue culture].

PMID- 15430939
TI  - [Toxic side effects of nitrogen mustard therapy].

PMID- 15430940
TI  - [Metabolism of sodium hyposulfite in leukemia; anticytostatic and hyperplastic
      action].

PMID- 15430941
TI  - [Behavior of blood phagocytes in chemotherapy].

PMID- 15430942
TI  - [Chronic hyperplastic panmyelosis].

PMID- 15430944
TI  - Experimental macrocytic anaemia in the rat.

PMID- 15430943
TI  - [Acute basophil and eosinophil leukosis].

PMID- 15430945
TI  - A new method for bone marrow culture.

PMID- 15430946
TI  - [Progressive abnormalities of erythropoiesis].

PMID- 15430947
TI  - [Topographically dissociated bone marrow syndromes and value of multiple
      medullary punctures].

PMID- 15430948
TI  - [Erythroblastic aspect in iron deficiency anemia and aplastic anemia, with
      special reference to infectious anemia].

PMID- 15430949
TI  - [Antianemic action of methionine].

PMID- 15430950
TI  - [Chemical nature of agglutination activators].

PMID- 15430951
TI  - Simultaneous determination of prothrombin and antithrombin activity of blood
      plasma by two-stage method; preliminary clinical observations.

PMID- 15430952
TI  - [Phenomenon of hemoglobin attraction].

PMID- 15430953
TI  - [Activity of heparin in experimental lesions of the liver].

PMID- 15430954
TI  - [Anticoagulant chemicals].

PMID- 15430955
TI  - [Experimental urethane agranulocytosis and panmyelopathy in the cat].

PMID- 15430956
TI  - [The virus of the leukemias].

PMID- 15430957
TI  - [Images of virus in the cells of human leukemias].

PMID- 15430958
TI  - [Electronic microscope aspect of hemocytoblasts in avian leukemia].

PMID- 15430959
TI  - [Consanguinity and Rh antagonism].

PMID- 15430960
TI  - [Monoblastic and monocytic leukemia].

PMID- 15430961
TI  - [Blastomycosis; diagnosis by lymph node puncture].

PMID- 15430962
TI  - [Certain aspects of endogenous nucleic catabolism in Biermer's disease treated by
      folic acid; contribution to the study of the megaloblast].

PMID- 15430963
TI  - [Biermer's anemia and gastric ulcer].

PMID- 15430964
TI  - [Acute purpura in the course of brucellosis, intramedullary autohemotherapy,
      arrest of hemorrhage].

PMID- 15430965
TI  - [A case of reticulo-myelosarcomatosis (Ewing's sarcoma)].

PMID- 15430966
TI  - [Bacterial hemolysins and antihemolysins].

PMID- 15430967
TI  - [Surgery of a peptic gastro-jejunal ulcer].

PMID- 15430968
TI  - [Tetraethylammonium therapy of pain in the shoulder].

PMID- 15430969
TI  - [Contributions to the diagnosis of horseshoe kidney].

PMID- 15430970
TI  - [Lead poisoning from water].

PMID- 15430971
TI  - [Classification of epilepsy].

PMID- 15430972
TI  - [Rheumatism and Addison's disease].

PMID- 15430973
TI  - [The problem of dental caries in the pregnant woman].

PMID- 15430974
TI  - [Case of tetanus with recovery].

PMID- 15430975
TI  - [Tracheo-bronchial stricture and endothoracic goiter].

PMID- 15430976
TI  - [A serious disease: obesity].

PMID- 15430977
TI  - [Tumor of the hypophysis].

PMID- 15430978
TI  - [Vitamin therapy and tuberculosis of the urinary tract].

PMID- 15430979
TI  - [Experimental psychology and psychiatry, an historical survey].

PMID- 15430980
TI  - [Positive and negative aspects of anatomicoclinical observations].

PMID- 15430981
TI  - [Pathology of the hypothalamus].

PMID- 15430982
TI  - [Psychoanalysis and metaphysics].

PMID- 15430983
TI  - [Toxic psychoses due to sedormid, saridon and contra-pain].

PMID- 15430984
TI  - [Geographic factors in the spread of multiple cerebrospinal sclerosis].

PMID- 15430985
TI  - [Psychologic significance of oxygen regulation in the fetus].

PMID- 15430986
TI  - [Differential diagnosis and therapy of myelopathy].

PMID- 15430987
TI  - [Anatomy of the hypothalamus and the greater subthalamic zone;
      cytoarchitectonics, conduction pathways, histophysiology].

PMID- 15430988
TI  - [Methods in investigation of organic dementia].

PMID- 15430989
TI  - [Oligodendroglioma; anatomicoclinical study of 74 cases].

PMID- 15430991
TI  - [Narco-analysis as an aid in psychotherapy].

PMID- 15430990
TI  - [Intracranial hypertension and brucellosis; brucellotic meningoencephalitis with
      clinical aspect of tumor].

PMID- 15430992
TI  - [Experimental and clinical studies of the dihydrogenated alkaloids of ergot of
      rye].

PMID- 15430993
TI  - [Relation of the hydergin-glucose test to psyche and constitution].

PMID- 15430994
TI  - [Excretion of barbituric acids in prolonged sleep therapy of schizophrenia].

PMID- 15430995
TI  - [Behavior of barbituric acids in the organism during sleep therapy of mental
      disease].

PMID- 15430996
TI  - [Not Available].

PMID- 15430997
TI  - [Not Available].

PMID- 15430998
TI  - [Two diaplacental infectious diseases and their effects on the central nervous
      system; toxoplasmosis and rubeola].

PMID- 15430999
TI  - [Purpose and activities of the Clinique de la Grangette].

PMID- 15431000
TI  - [Case histories and biogenetic analysis of malformations of the central nervous
      system].

PMID- 15431001
TI  - [Anatomopathological findings in cerebral injury due to obstetrical forceps].

PMID- 15431002
TI  - [Personality development in adiposogenital dystrophy].

PMID- 15431003
TI  - [Not Available].

PMID- 15431004
TI  - [Not Available].

PMID- 15431005
TI  - [Commemoration of the birth of Auguste Forel].

PMID- 15431006
TI  - [Role of the hypothalamus in autonomic regulation].

PMID- 15431007
TI  - [Effect of peripheral autonomic disorders on spinal cord function].

PMID- 15431008
TI  - [Disorders of circulatory regulation of central nervous origin following open and
      blunt injury of the brain].

PMID- 15431009
TI  - [The hypothalamic nuclei in the light of certain histopathologic processes, with
      special reference to Alzheimer's disease].

PMID- 15431010
TI  - [Disorders of the autonomic nervous system following cerebral injury].

PMID- 15431011
TI  - [Midbrain psychopathy in Cushing's disease].

PMID- 15431012
TI  - [Not Available].

PMID- 15431013
TI  - [Not Available].

PMID- 15431014
TI  - [Not Available].

PMID- 15431015
TI  - [Not Available].

PMID- 15431016
TI  - [Not Available].

PMID- 15431017
TI  - [Not Available].

PMID- 15431018
TI  - [Erythrocyte sedimentation, rate, and hemoglobin content in the half-blood
      horse].

PMID- 15431019
TI  - [Effect of abnormal proportions of fodder upon calcium, magnesium and phosphate
      metabolism in cattle].

PMID- 15431020
TI  - [Characteristics and production of cross-bred offspring of Yugoslavian domestic
      and Swiss Saanen goats].

PMID- 15431021
TI  - [Unusual case of hyperplasia glandularis cystica following ovariotomy subsequent
      to ligation of the uterine horns in a young bitch].

PMID- 15431022
TI  - [The practical significance of the Rh factor in blood transfusion; management of
      a complication with peritoneal dialysis].

PMID- 15431023
TI  - [Irregular agglutinins in transfusion shock].

PMID- 15431024
TI  - [Intraperitoneal lavage in the treatment of acute renal insufficiency].

PMID- 15431025
TI  - [Epileptiform attacks in thallium poisoning].

PMID- 15431026
TI  - [Alkali-plasma transfusion].

PMID- 15431028
TI  - [Pathogenesis and pathological anatomy of hypertension].

PMID- 15431027
TI  - [Humeral luxation into the thoracic cavity].

PMID- 15431029
TI  - [The differential diagnosis of hypertension as a problem in pathogenesis].

PMID- 15431030
TI  - [Surgical therapy of arterial hypertension].

PMID- 15431031
TI  - [Medicinal treatment of essential hypertension].

PMID- 15431032
TI  - [Pseudo-tumoral syndrome of arterial hypertension].

PMID- 15431033
TI  - [Experimental investigations on renal circulation; renal ischemia following
      administration of histamine].

PMID- 15431034
TI  - [Relation between the glomerular filtrate, the urea content of the blood, and
      Volhard's rarefaction and concentration test].

PMID- 15431035
TI  - [Fluorinated salt in caries prophylaxis].

PMID- 15431036
TI  - [Arthrogryposis multiplex congenita, a not infrequent, but rarely described
      deformity].

PMID- 15431037
TI  - [Simple treatment of certain forms of obesity].

PMID- 15431038
TI  - [An epidemic of Q fever].

PMID- 15431039
TI  - [Spasmolytic effect of phenobarbital, and a complex association of total extracts
      of Datura and Scopolia (sanalepsi); their respective antidotal effect to
      cardiazol, and their differential toxicity].

PMID- 15431040
TI  - [A suit involving pharmaceutical corporations, Pharmac S. A. and Pharmacal S.
      A..].

PMID- 15431041
TI  - [Dispensing of alcoholic beverages by apothecaries and the Zurich law governing
      retail establishments].

PMID- 15431042
TI  - [Oxygen deficiency].

PMID- 15431043
TI  - [Myotonic dystrophy and cranial hyperostosis].

PMID- 15431044
TI  - [Mechanism and regulation of iron resorption].

PMID- 15431045
TI  - [Medicinal therapy of lung abscesses and their pleural complications; importance
      of local therapy].

PMID- 15431046
TI  - [Oxymetric control of oxygen deficiency].

PMID- 15431047
TI  - [Differential diagnostic difficulties of tuberculosis of the knee joint in
      children].

PMID- 15431048
TI  - [Suction drainage of pulmonary caverns and thoracoplasty].

PMID- 15431049
TI  - [Side effects of streptomycin].

PMID- 15431050
TI  - [Intracavernous injection of streptomycin in the treatment of pulmonary
      tuberculosis].

PMID- 15431051
TI  - Concerning the theory of photoconductivity in infrared-sensitive semiconducting
      films.

PMID- 15431052
TI  - Hemolytic activity of some nonionic surface-active agents.

PMID- 15431053
TI  - The inhibitory effect of three antihistamine compounds on the growth of fungi
      pathogenic for man.

PMID- 15431054
TI  - Triphenyltetrazolium chloride in tissue culture.

PMID- 15431055
TI  - A modification of the Hardy-Weinberg law.

PMID- 15431056
TI  - A simple pulsating perfusion apparatus.

PMID- 15431057
TI  - Calorimetric method for the determination of the surface energy of a brittle
      crystalline solid.

PMID- 15431058
TI  - Some derivatives of diphenyldisulfide with antispirochetal activity.

PMID- 15431059
TI  - New method for blood pressure recording.

PMID- 15431060
TI  - Comments and communication.

PMID- 15431061
TI  - Committee for aid to foreign physiologists.

PMID- 15431062
TI  - Education and training for ocenographers.

PMID- 15431063
TI  - [International Colloquium on Theoretical Physics].

PMID- 15431064
TI  - Carl Emil Seashore, 1866-1949.

PMID- 15431065
TI  - An agglutinin in normal sera for periodate-treated red cells.

PMID- 15431066
TI  - Reduction of mortality from X-radiation by treatment with antibiotics.

PMID- 15431067
TI  - New chemotherapeutic agents in enterohepatitis (blackhead) of turkeys.

PMID- 15431068
TI  - Effect of adrenalectomy on liver catalase activity in the rat.

PMID- 15431070
TI  - Hemophilia in the female dog.

PMID- 15431069
TI  - An apparatus for localizing warm and cold receptors.

PMID- 15431071
TI  - Diabetogenic effect of dehydroglucoascorbic acid.

PMID- 15431073
TI  - [The chromosomes of the salivary glands of Drosophila subobscura Collin].

PMID- 15431072
TI  - Otto Struve on the freedom of science.
AB  - The article "Antifolliculoid Activity of Vitamin A" (Kahn, Raymond H. and Bern,
      Howard A., Science, 1950, 111, 516) contains an error. The words ". . . and
      inactivate," at the end of the first line, paragraph 2, p. 516, should be
      deleted.

PMID- 15431074
TI  - [Heteropycnosis of the autosomes as possible mechanism of speciation; cytological
      research in some neotropical Hemiptera].

PMID- 15431076
TI  - [Spermatogenesis of Psychoda alternata Say and of Psychoda cinerea Banks (Dipt.
      Psychodidae)].

PMID- 15431075
TI  - [First observations on the cytology of Phasmidase of Brazil].

PMID- 15431077
TI  - [Further observations on the so strain of Drosophila melanogaster].

PMID- 15431078
TI  - [Sterility of the hybrids of the genus Anopheles; sterility in the cross between
      Anopheles mac. atroparvus and Anopheles mac. typicus and in the re cross of the
      salivary chromosomes].

PMID- 15431079
TI  - [Genetics and general biology].

PMID- 15431080
TI  - [Hypersplenia and hypersplenic syndromes].

PMID- 15431081
TI  - [Infrequent diseases of the digestive system; Strongyloides stercoralis and
      Fasciola hepatica].

PMID- 15431082
TI  - [New treatment of idiopathic pruritus].

PMID- 15431083
TI  - [Ultrasonics therapy; review of foreign bibliography].

PMID- 15431084
TI  - [Seroprophylaxis and serotherapy in certain common diseases in the army].

PMID- 15431085
TI  - [The Zarate symphysiotomy with regard to the problem of cephalopelvic
      disproportion].

PMID- 15431086
TI  - [Giant follicular lymphoma of the cecal appendix].

PMID- 15431087
TI  - [Treatment of hay fever with antihistamines].

PMID- 15431088
TI  - [Second session of the Committee of Experts of the World Health Organization
      meeting in Geneva].

PMID- 15431089
TI  - [Cystic gliomas with inextirpable mural nodules: therapeutic management].

PMID- 15431090
TI  - [A new technic for the Hanger reaction].

PMID- 15431091
TI  - [Seminar of pathology, clinical medicine and surgical technic; cystic tumor of
      the lung].

PMID- 15431092
TI  - [Dr. Ernesto V. Merlo].

PMID- 15431093
TI  - [Surgical physiopathology of ulcer].

PMID- 15431094
TI  - [Immediate analytic diagnosis with the aid of microlaboratories].

PMID- 15431095
TI  - [Treatment of syphilis and the serological response. II. Massive arsenotherapy;
      penicillinotherapy].

PMID- 15431096
TI  - [Craniosclerosis with calcareous pachymeningeal dysfibrosis].

PMID- 15431097
TI  - [Action of vitamin E in acute glomerulonephritis].

PMID- 15431098
TI  - [Seminar of pathology, clinical medicine, and surgical technic; intestinal
      obstruction due to adhesions].

PMID- 15431099
TI  - [Respirator therapy in infantile paralysis].

PMID- 15431100
TI  - [Swimming cramps as a cause of accidental drowning. Part II].

PMID- 15431101
TI  - [Medical views on the purity of the water supply].

PMID- 15431102
TI  - Acute intestinal obstruction, with special reference to closed loop and
      strangulating lesions in the Bantu; a clinical study.

PMID- 15431103
TI  - The syndrome of malignant malnutrition; observations on the relation of the serum
      proteins to the occurrence of oedema and the effect of diet.

PMID- 15431104
TI  - Gravitational leg syndromes.

PMID- 15431105
TI  - Problems associated with the pharmacology and clinical usage of curare.

PMID- 15431106
TI  - Trachoma in the South African Bantu.

PMID- 15431107
TI  - Observations on the Proetz displacement therapy in sinusitis; a demonstration of
      the technique.

PMID- 15431108
TI  - The premature infant; a new approach in its management.

PMID- 15431109
TI  - Alcoholism--a national public health emergency.

PMID- 15431110
TI  - Diagnosis and treatment of poliomyelitis in the acute stage.

PMID- 15431111
TI  - Poliomyelitis; post-paralytic treatment--orthopaedic aspect.

PMID- 15431112
TI  - NEW preparations and appliances; stigminene bromide 'Warner' (1-benzyl-3
      (dimethylcarbamyloxy)-pyridinium bromide).

PMID- 15431113
TI  - The heart as a target in psychological disturbances.

PMID- 15431114
TI  - The approach to vasomotor rhinitis.

PMID- 15431115
TI  - The value of ophthalmodynamometry in general medicine.

PMID- 15431116
TI  - Closed injuries of the kidney.

PMID- 15431117
TI  - Q fever; serological evidence of the occurrence of a case in South Africa.

PMID- 15431118
TI  - The laboratory diagnosis of tuberculous meningitis.

PMID- 15431119
TI  - Leiomyomata of the stomach.

PMID- 15431120
TI  - Excretory urography in the young subject; hyaluronidase and tomography as aids.

PMID- 15431121
TI  - Pancreatic abscess; its radiological features.

PMID- 15431122
TI  - A case of turner's syndrome with coarctation of the aorta and a pulmonary,
      arterio-venous aneurysm.

PMID- 15431123
TI  - Ureteric calculi; the application of basic principles in their conservative
      management.

PMID- 15431124
TI  - Health centres; a memorandum for the information of government officers.

PMID- 15431125
TI  - Bantu syphilis; a report of 184 cases.

PMID- 15431126
TI  - The present status of the treatment of hyperthyroidism.

PMID- 15431127
TI  - Headache, functional and organic.

PMID- 15431128
TI  - Intravenous procaine therapy; an evaluation of the results in 245 cases of
      various pain disorders.

PMID- 15431129
TI  - Carbowax embedding for obtaining thin tissue sections and study of intracellular
      lipids.

PMID- 15431130
TI  - Staining and recognition of fine, degenerating nerve fibers.

PMID- 15431131
TI  - An aceto-carmine squash technic for amphibian chromosomes.

PMID- 15431132
TI  - Staining similarity of Foot's and HIO4-Schiff technics.

PMID- 15431133
TI  - A smear technic for the Cucurbitacae.

PMID- 15431134
TI  - An apparatus for fixation and supravital staining of tissues by the perfusion
      method.

PMID- 15431135
TI  - An improved arginine histochemical method.

PMID- 15431136
TI  - The differentiated silver impregnation of certain conducting pathways in the
      peripheral nervous system.

PMID- 15431137
TI  - A simplified bacterial spore stain.

PMID- 15431138
TI  - Schistosoma mansoni miracidium under phase difference microscopy.

PMID- 15431139
TI  - Softening refractory plant material embedded in paraffin.

PMID- 15431140
TI  - Supravital staining of mitochondria with amethyst violet.

PMID- 15431141
TI  - [Determination of benzol and toluol in petroleum benzin].

PMID- 15431142
TI  - [Not Available].

PMID- 15431143
TI  - [Arsenic trioxide tablets, 1 mg].

PMID- 15431144
TI  - [Nomenclature accepted by the Board of the Norwegian Pharmacopeia].

PMID- 15431145
TI  - [The pharmacy in MArsil].

PMID- 15431146
TI  - [In memoriam Johan Lybing].

PMID- 15431148
TI  - [Antihistamine].

PMID- 15431147
TI  - [Testing purity with the help of the limitation test].

PMID- 15431149
TI  - [Recent acquisitions of the library of Royal Pharmacological Institute].

PMID- 15431150
TI  - [Compensation for tax reduction].

PMID- 15431151
TI  - [Personnel regulations].

PMID- 15431152
TI  - [Caries in the deciduous teeth and the most common sequels, with special
      reference to therapy].

PMID- 15431153
TI  - [Dental materials and their use: cement].

PMID- 15431154
TI  - [The problems of hospital organization in the United States].

PMID- 15431155
TI  - [The 3 steps in the exploration of the electric currents of cardiac origin].

PMID- 15431156
TI  - [The technology of vectorcardiography].

PMID- 15431157
TI  - [The problem of surgical lighting].

PMID- 15431159
TI  - [The responsibility of hospitals, this sword of Damocles].

PMID- 15431158
TI  - [The new hospital and home for the aged of Sainte Marieaux-Mines, Haut-Rhin].

PMID- 15431160
TI  - [The distribution of food in hospitals].

PMID- 15431161
TI  - [Influence of the Institute Pasteur on bacteriology in Turkey].

PMID- 15431162
TI  - [A pressing problem: the placement of cases of pulmonary tuberculosis in the
      Parisian area].

PMID- 15431163
TI  - [Organization and functioning of a modern pneumology and phthisiology service].

PMID- 15431164
TI  - [The new maternity unit of the Hopital de Montmorency].

PMID- 15431165
TI  - [Commercial production and distribution of formulas for infant feeding].

PMID- 15431166
TI  - [A plan for the centralization of supplies in a small hospital].

PMID- 15431167
TI  - [Tables on the composition of food].

PMID- 15431168
TI  - [Text of laws and administrative rulings].

PMID- 15431169
TI  - [Plan for a departmental obstetrical center].

PMID- 15431170
TI  - [Sterilization of air by ultraviolet rays].

PMID- 15431171
TI  - [The Briancon Hospital].

PMID- 15431172
TI  - [The legal responsibilities of the members of the Administrative Hospital
      Commission].

PMID- 15431173
TI  - [Organization of a blood transfusion service by the Dutch Red Cross].

PMID- 15431174
TI  - [The electronic polystethoscope].

PMID- 15431175
TI  - [History of hospital organization].

PMID- 15431176
TI  - [Creation of seaside preventoriums].

PMID- 15431177
TI  - [Insect repellents in hospital practice].

PMID- 15431179
TI  - [The financing of hospital expenses; criticism of the practice of a per diem
      fee].

PMID- 15431178
TI  - [The Priory, rest home for women at Avon-Fontainebleau].

PMID- 15431180
TI  - [The per diem fee in private and social insurance establishments].

PMID- 15431181
TI  - [Tables on the composition of foods].

PMID- 15431182
TI  - [Comfort and consolation of the patient; the question of uniform clothing for
      patients in public hospitals].

PMID- 15431183
TI  - Role of radioisotopes in blood dyscrasias and neoplastic diseases.

PMID- 15431184
TI  - Drug therapy in management of neoplastic disease.

PMID- 15431185
TI  - Nitrogen mustards in the treatment of malignant disease.

PMID- 15431186
TI  - Use of artane in parkinsonism.

PMID- 15431187
TI  - Unexpected fatality in a child from accidental consumption of antiasthmatic
      preparation containing ephedrine, theophylline and phenobarbital.

PMID- 15431188
TI  - Severe leukopenia due to diphenylhydantoin sodium; case report.

PMID- 15431189
TI  - Tumors of the mediastinum.

PMID- 15431190
TI  - Diagnosis of primary cardiac neoplasms.

PMID- 15431192
TI  - The pathologist's responsibility in diagnosis and treatment of cancer.

PMID- 15431191
TI  - Carcinoma of the colon and rectum; review of 554 cases from 1918 to 1943.

PMID- 15431193
TI  - Tumor seminar.

PMID- 15431194
TI  - Severe reactions from insect stings.

PMID- 15431195
TI  - Osteoma of the frontal sinus.

PMID- 15431196
TI  - Intravaginal roentgen therapy of carcinoma of cervix; preliminary report on 14
      cases.

PMID- 15431197
TI  - [Treatment of Bang's disease with streptomycin and sulfadiazine].

PMID- 15431198
TI  - [Operative therapy of inflammatory adnexal tumors].

PMID- 15431199
TI  - [Examination and comparison of present prophylactic sunburn preparations].

PMID- 15431201
TI  - [Treatment of enuresis].

PMID- 15431200
TI  - [The protein problem in medicine].

PMID- 15431202
TI  - [Treatment of diseases of the joints with adrenocortical hormones, with a
      preliminary report on the combined use of desoxycorticosterone acetate and l
      ascorbic acid].

PMID- 15431203
TI  - [The effect of opiate alkaloids (pavium "forte")].

PMID- 15431204
TI  - [Laboratory experiences with penicillin preparations for retarded action].

PMID- 15431205
TI  - [Experiences with penicillin preparations for retarded action in venereology].

PMID- 15431206
TI  - [Experiences with penicillin preparations for retarded action in internal
      medicine].

PMID- 15431207
TI  - [Experiences with penicillin preparations for retarded action in the treatment of
      surgical diseases].

PMID- 15431208
TI  - [Acute and chronic protein deficiency].

PMID- 15431209
TI  - [Whooping cough].

PMID- 15431210
TI  - [Birds and trichinosis; pathology and transmission].

PMID- 15431211
TI  - [Conservative treatment methods of peripheral circulatory disorders; a critical
      summary of therapeutic measures].

PMID- 15431212
TI  - [Treatment of local tuberculous ulcers which occasionally appear in
      intracutaneous application of BCG vaccination].

PMID- 15431213
TI  - [Experiences with azoangin as a urinary antiseptic].

PMID- 15431214
TI  - Cystic hygroma of the mediastinum.

PMID- 15431215
TI  - Final results in traumatic haemothorax; a report of 230 cases.

PMID- 15431216
TI  - Congenital right diaphragmatic hernia associated with Fallot's tetralogy.

PMID- 15431217
TI  - Leiomyoma of the bronchus.

PMID- 15431218
TI  - Development of streptomycin resistant strains of tubercle bacilli in pulmonary
      tuberculosis; results of simultaneous sensitivity tests in liquid and on solid
      media.

PMID- 15431219
TI  - The behaviour of mixtures of streptomycin-sensitive and -resistant tubercle
      bacilli in liquid medium sensitivity tests.

PMID- 15431220
TI  - Unilateral paralysis of the diaphragm and larynx associated with inflammatory
      lung disease.

PMID- 15431221
TI  - Apico-basal diameters of the lungs and mediastinal shift in phrenic nerve crush
      and pneumoperitoneum therapy; a study of eighty cases.

PMID- 15431222
TI  - A modified conception of phrenic nerve crush and pneumoperitoneum therapy.

PMID- 15431223
TI  - [Not Available].

PMID- 15431224
TI  - [Preparation of sludge and plasma on a small scale].

PMID- 15431225
TI  - [Lung cancer in nickel workers].

PMID- 15431226
TI  - [Malignant tumors of the testicle].

PMID- 15431227
TI  - [Not Available].

PMID- 15431228
TI  - [Medical certifications].

PMID- 15431229
TI  - [Rules governing the appointment of candidates and doctors of comparable status].

PMID- 15431230
TI  - [Shortage of doctors in Sweden?].

PMID- 15431231
TI  - [Health centers in rural districts].

PMID- 15431232
TI  - [Financial statement for 1949 of the Norwegian Medical Society].

PMID- 15431233
TI  - [Calciferol therapy, with special reference to danger of poisoning in patients
      with Boeck sarcoid].

PMID- 15431234
TI  - [Measles encephalitis].

PMID- 15431235
TI  - [A year's activity of the Ulleval blood bank].

PMID- 15431236
TI  - [Sickness insurance benefits for physical and hydrotherapy].

PMID- 15431237
TI  - [Malignant melanomas and malignant nevoid tumors].

PMID- 15431238
TI  - [Medical certifications].

PMID- 15431239
TI  - [Medical services in the U.S.A..].

PMID- 15431240
TI  - [Evaluation of the early diagnosis of uterine cancer by Papanicolaou's method].

PMID- 15431241
TI  - [Cherney's incision and its application to a new technic of extraperitoneal
      cesarean section].

PMID- 15431242
TI  - [A curious case of imperforate hymen and urethral coitus].

PMID- 15431243
TI  - [Biological diagnosis of pregnancy].

PMID- 15431244
TI  - [Obliterating vaginal atresia].

PMID- 15431246
TI  - [New therapeutics for chronic alcoholism].

PMID- 15431245
TI  - [Simple instrument for the diagnosis and therapy of female sterility].

PMID- 15431247
TI  - [Reflections on a subject of current interest in French West Africa: leprosy].

PMID- 15431248
TI  - [Colibacillosis is primarily a constitutional weakness].

PMID- 15431249
TI  - [Stifling in digestive disorders and treatment by pituitary].

PMID- 15431250
TI  - [Perivisceritis and its treatment].

PMID- 15431251
TI  - [Modern procedures for the treatment of rheumatic fever and its cardiac
      complications].

PMID- 15431252
TI  - [A case of submaxillary lithiasis].

PMID- 15431253
TI  - [Cruciform arthrodesis of the knee].

PMID- 15431254
TI  - [Delayed ulnar paralysis following resection of the radial head for an
      irreducible Monteggia's fracture].

PMID- 15431255
TI  - [Lithotrity under radioscopic control].

PMID- 15431256
TI  - [Hydronephrosis in a horseshoe kidney].

PMID- 15431257
TI  - [A pseudomyopathic form of the Guillain-Barre syndrome].

PMID- 15431258
TI  - [Radiological study of the sphenoid fissure].

PMID- 15431259
TI  - [Use of streptomycin in pulmonary tuberculosis].

PMID- 15431261
TI  - The hospital in the rural community.

PMID- 15431260
TI  - The value of pulmonary function tests in the diagnosis of pulmonary disease.

PMID- 15431262
TI  - Memoir of Henry D. Jump.

PMID- 15431263
TI  - Memoir of Arthur Parker Hitchens.

PMID- 15431264
TI  - Memoir of Augustus Adolph Eshner.

PMID- 15431265
TI  - Memoir of John Claxton Gittings.

PMID- 15431266
TI  - CATALOGUE of the Mutter Museum of the College of Physicians of Philadelphia;
      supplementary index to donors and the specimens donated by them.

PMID- 15431267
TI  - CATALOGUE of oil portraits in the College of Physicians of Philadelphia, 1950.

PMID- 15431268
TI  - MORTALITY trend.

PMID- 15431269
TI  - The nature of drugfastness.

PMID- 15431270
TI  - The combined use of paraaminosalicylic acid (PAS) and streptomycin in pulmonary
      tuberculosis.

PMID- 15431271
TI  - Combined streptomycin-para-aminosalicylic acid treatment of pulmonary
      tuberculosis.

PMID- 15431272
TI  - Freeze-dried (lyophilized) BCG.

PMID- 15431273
TI  - Boeck's sarcoidosis (chronic epithelioid-celled reticulo-endotheliosis or
      granulomatosis).

PMID- 15431274
TI  - A tuberculous cow.

PMID- 15431276
TI  - [Hans Thomsen on his 60th birthday].

PMID- 15431275
TI  - Vaccination with freeze-dried BCG preliminary clinical reports.

PMID- 15431277
TI  - [Investigation on the mode of action of pneumoperitoneum with special reference
      to roentgenkymography].

PMID- 15431278
TI  - [Etiology and therapy of spontaneous pneumothorax].

PMID- 15431279
TI  - [Intracavernous injections of chemotherapeutic agents in children and young
      people].

PMID- 15431280
TI  - [Treatment of superior lobe cavity by neurotomy and pneumoperitoneum].

PMID- 15431281
TI  - [Evaluation of sugar determination in pleural puncture for the diagnosis of
      exudative pleurisy].

PMID- 15431282
TI  - [Symptomatology and therapy of dry pleurisy].

PMID- 15431283
TI  - [Increased thiosemicarbazone tolerance through laevoral, a liver protective
      substance].

PMID- 15431284
TI  - [Contralateral pneumothorax and thoracoplasty].

PMID- 15431285
TI  - [Chemotherapy of laryngeal tuberculosis].

PMID- 15431286
TI  - [Experiences with blood sedimentation accelerated by collodion].

PMID- 15431287
TI  - [Streptomycin therapy in hematogenous form of tuberculosis in childhood; comments
      on a report by Pies].

PMID- 15431288
TI  - [Roentgen examination of the population of Kie].

PMID- 15431289
TI  - [Ultrasonics and pulmonary tuberculosis].

PMID- 15431290
TI  - [Physical peculiarities of ultrasound].

PMID- 15431291
TI  - [Detection of morphine and its derivatives in the urine of heroin and morphine
      addicts].

PMID- 15431292
TI  - [Interesting abdominal tumor].

PMID- 15431293
TI  - [Experiences with place tal transplantation].

PMID- 15431294
TI  - [Partial nephrectomy and total uretero-nephrectomy in renal tuberculosis].

PMID- 15431295
TI  - [Synovial chondromata in the knee joint].

PMID- 15431296
TI  - The simulation of heart disease.

PMID- 15431297
TI  - The problem of the aged in mental hospitals.

PMID- 15431298
TI  - The obstetrical aspects of Tristram Shandy.

PMID- 15431299
TI  - A survey of haemoglobin levels of children attending the Royal Belfast Hospital
      for Sick Children.

PMID- 15431300
TI  - BCG vaccination in Stockholm.

PMID- 15431301
TI  - BCG.

PMID- 15431302
TI  - Home care for sick persons organized by hospitals.

PMID- 15431303
TI  - Isolated (Fiedler's) myocarditis.

PMID- 15431304
TI  - Rheumatic heart disease in pregnancy.

PMID- 15431305
TI  - Heart disease and pregnancy.

PMID- 15431306
TI  - Neo-natal surgery.

PMID- 15431307
TI  - Neo-natal anaesthesia.

PMID- 15431308
TI  - A case of ureterocele in an infant.

PMID- 15431309
TI  - Hepatitis and its sequelae.

PMID- 15431310
TI  - Naso-pharyngeal fibroma.

PMID- 15431311
TI  - Kippel-Feil syndrome, and associated congenital abnormalities.

PMID- 15431312
TI  - Athetosis.

PMID- 15431313
TI  - The painful shoulder.

PMID- 15431314
TI  - [Nutrition and dental caries, interpretation of the role of nutrition in the
      pathogenesis of dental caries].

PMID- 15431315
TI  - [PAS: history and clinical and experimental study at the Hopital du Sacre-Coeur].

PMID- 15431316
TI  - [Biological study of an estrogen complex active when administered orally].

PMID- 15431317
TI  - [Case of decalcifying myeloma or Kahler's disease].

PMID- 15431318
TI  - [Vitamin B12].

PMID- 15431319
TI  - [Volvulus of the stomach: a case].

PMID- 15431320
TI  - [Arterial pressure].

PMID- 15431322
TI  - [Our common cause against cancer].

PMID- 15431321
TI  - [Diuretics].

PMID- 15431323
TI  - [Epidemics of yesterday].

PMID- 15431324
TI  - [Acute meningitis; a case].

PMID- 15431325
TI  - [Pregnancy and intestinal occlusion].

PMID- 15431326
TI  - [Toxic angina].

PMID- 15431327
TI  - [Parinaud's oculo-glandular syndrome].

PMID- 15431328
TI  - [Not Available].

PMID- 15431329
TI  - [A case of nanism].

PMID- 15431330
TI  - [Secondary sarcoma of the lung].

PMID- 15431331
TI  - [Application of new methods and new concepts to the study of collagenic disorders
      in scleroderma].

PMID- 15431332
TI  - [Not Available].

PMID- 15431333
TI  - [Exophthalmia].

PMID- 15431334
TI  - [Diverticula of the urethra with calculi in women].

PMID- 15431335
TI  - [Choroiditis guttata].

PMID- 15431336
TI  - [Syncope].

PMID- 15431337
TI  - [Hernioplasty with tantalum gauze].

PMID- 15431338
TI  - [The family physician and progress of health].

PMID- 15431339
TI  - [The evolution of the Health Service; present organization of the Montreal Health
      Service].

PMID- 15431341
TI  - [Thoracic tumors].

PMID- 15431340
TI  - [Cancer of the lung; bronchial carcinoma].

PMID- 15431342
TI  - [Cardiovascular diseases requiring surgery].

PMID- 15431343
TI  - [Total abdomino-thoracic gastrectomy].

PMID- 15431344
TI  - [Cerebral and medullar tumors].

PMID- 15431345
TI  - [Poliomyelitis, infectious disease or metabolic disorder?].

PMID- 15431346
TI  - [Recurrent dislocation of the shoulder].

PMID- 15431347
TI  - [Cancer of the uterine body].

PMID- 15431348
TI  - [Orbito-frontal headache and ophthalmoplegia due to intracranial carotid
      aneurysm].

PMID- 15431349
TI  - [Hydronephrosis with gastrointestinal symptomatology].

PMID- 15431350
TI  - [Pregnancy and tuberculosis].

PMID- 15431352
TI  - [Cerebral angiography].

PMID- 15431351
TI  - [The fundus oculi in hypertension].

PMID- 15431353
TI  - [Facts on Federal health subsidies].

PMID- 15431354
TI  - [Present organization of the Health Service of Montreal].

PMID- 15431355
TI  - [Sanitation at vacation sites].

PMID- 15431356
TI  - [French medicine yesterday and today in Canada].

PMID- 15431357
TI  - [Control of weight, diet and osmotic balance during pregnancy].

PMID- 15431358
TI  - [Convulsions and teething].

PMID- 15431359
TI  - [Pancoast syndrome].

PMID- 15431360
TI  - [Vitamin E in the treatment of cardiovascular disease].

PMID- 15431361
TI  - [Failure of antihistamine treatment of atopic dermitis].

PMID- 15431362
TI  - [Allergic headache].

PMID- 15431363
TI  - [A case of giardiasis].

PMID- 15431364
TI  - Tumors of the testes; 5-year follow-up study.

PMID- 15431365
TI  - Torsion of the spermatic cord.

PMID- 15431366
TI  - Primary bronchogenic carcinoma.

PMID- 15431367
TI  - The ante-mortem diagnosis of secondary tumors of the heart.

PMID- 15431368
TI  - Idiopathic thrombocytopenic purpura; splenectomy and toluidine blue in treatment.

PMID- 15431369
TI  - Bilateral circumscribed pretibial myxedema; report of a case.

PMID- 15431370
TI  - Syndrome of circumoral pigmentation associated with generalized intestinal
      polyposis; report of a case.

PMID- 15431372
TI  - Glanders.

PMID- 15431371
TI  - Cutaneous diphtheria.

PMID- 15431373
TI  - Foot-and-mouth disease in Mexico.

PMID- 15431374
TI  - Bony lesions occurring during the early stages of syphilis; report of a case.

PMID- 15431375
TI  - Fractures of the mandibular condyle; report of 8 cases.

PMID- 15431376
TI  - Toxicity of intrathecal penicillin.

PMID- 15431377
TI  - Mosquito control problems in Japan.

PMID- 15431378
TI  - A method for testing sensitivity of organisms to antibiotics.

PMID- 15431379
TI  - About the Army Medical Department; the new Army and Air Force interns.

PMID- 15431381
TI  - Field training of army medical officers.

PMID- 15431380
TI  - The station hospital as a diagnostic and treatment center.

PMID- 15431382
TI  - Fundamentals in the use and preservation of homogenous bone.

PMID- 15431383
TI  - Osteitis fibrosa cystica of the rib.

PMID- 15431384
TI  - An epidemic of vomiting and diarrhea.

PMID- 15431385
TI  - Cryptococcus neoformans meningo-encephalitis; report of a fatal case.

PMID- 15431386
TI  - Pentothal sodium anesthesia for vaginal delivery.

PMID- 15431387
TI  - Cyst of the mandible: report of a case with prosthetic restoration.

PMID- 15431388
TI  - Erythema exudativum multiforme (Stevens-Johnson syndrome).

PMID- 15431389
TI  - Listerella monocytogenes meningitis; report of a case.

PMID- 15431390
TI  - The retromolar area; its significance in full and partial denture construction.

PMID- 15431391
TI  - The Hanger cephalin cholesterol flocculation test and the Maclagan thymol
      turbidity test; correlation with autopsy findings.

PMID- 15431392
TI  - Anterior fixed bridges; a technique for construction by means of one-piece
      casting.

PMID- 15431393
TI  - Hemagglutination by neurotropic viruses.

PMID- 15431394
TI  - Laceration of the vaginal vault after normal coitus; report of a case.

PMID- 15431395
TI  - The clinical use of antibiotics; pharmacology and toxicology.

PMID- 15431396
TI  - Acute abdominal manifestations of ancylostomiasis; report of 2 cases.

PMID- 15431397
TI  - The transition of the citizen into the wartime armed forces.

PMID- 15431398
TI  - About the Army Medical Department; Medical Department extension courses.

PMID- 15431399
TI  - [Hospital economics].

PMID- 15431400
TI  - [From the Report of the Activity of the Swiss Association of Licensed Nurses and
      Nurses Aids].

PMID- 15431401
TI  - [A round of my hospital].

PMID- 15431402
TI  - [University-Canton Hospital of Lausanne, its mission and its relations with the
      regional hospitals].

PMID- 15431403
TI  - [Concerning a change in hospital duty hours].

PMID- 15431404
TI  - [Mitrofan Feofanovich Tsitovich, 1869-1936].

PMID- 15431405
TI  - [Otorhinolaryngology in relation to the increased 6 year course of medicine].

PMID- 15431406
TI  - [Progress in the problem of rhinoscleroma in Soviet Union].

PMID- 15431407
TI  - [Otogenous intracranial complications; clinical studies].

PMID- 15431408
TI  - [Otogenous meningitis and evaluation of its therapy according to data from
      Leningrad Laryngological Institute].

PMID- 15431409
TI  - [Differential diagnosis of otogenous and tuberculous meningitis].

PMID- 15431410
TI  - [Penicillin therapy in scarlatinal mastoiditis].

PMID- 15431411
TI  - [Syndrome of the sphenopalatine ganglion].

PMID- 15431412
TI  - [Tonsillectomy on the day following incision of a peritonsillar abscess].

PMID- 15431414
TI  - [Method of surgical therapy of grave defects of the nose].

PMID- 15431413
TI  - [Method of restoration of external auditory canal in adhesions].

PMID- 15431415
TI  - [Modified method of surgery of Highmore's antrum].

PMID- 15431416
TI  - [Permanent sutures in injuries of the frontal sinuses].

PMID- 15431417
TI  - [A new method of treatment of genuine ozena].

PMID- 15431418
TI  - [Method of determining the mobility of foreign bodies in the bronchi].

PMID- 15431419
TI  - [Method in treatment of cicatricial strictures of the esophagus].

PMID- 15431420
TI  - [Case of petrositis].

PMID- 15431421
TI  - [Injury of the auditory system by lightning].

PMID- 15431422
TI  - [Mitrofan Feofanovich Tsitovich, 1869-1936].

PMID- 15431423
TI  - [Docent Iakov Davidovich Missionzhnik].

PMID- 15431424
TI  - [Dermatology; its place in biologic sciences and problems].

PMID- 15431425
TI  - [Progress in dermato-mycology in the Soviet Union].

PMID- 15431426
TI  - [Pathergometry as a method of functional test of the skin].

PMID- 15431427
TI  - [Desensibilization effect of insulin in allergic occupational dermatitis].

PMID- 15431428
TI  - [Significance of residual carbon dioxide in the blood in eczema, lichen herpes
      and pyoderma].

PMID- 15431429
TI  - [Dynamics of the effect of balneotherapy in dermatoses as an index of the
      mechanism of balneological factors].

PMID- 15431430
TI  - [Soft roentgen rays in the therapy of eczema].

PMID- 15431431
TI  - [Effect of complex therapy (Matsesta cure) on the functional state of the
      physiologic system of the connective tissues in certain diseases of the skin].

PMID- 15431432
TI  - [Role of yeast-like fungi in eczema].

PMID- 15431433
TI  - [A. N. Maklakov and his role in application of ultraviolet rays in dermatology].

PMID- 15431434
TI  - [Contribution of P. V. Nikol'skii to Soviet dermatology and venerology].

PMID- 15431435
TI  - [Effect of the weather on eczema].

PMID- 15431436
TI  - [Photo-allergy; a case of local facial photo-allergy, following photodermatitis].

PMID- 15431437
TI  - [Lichen ruber planus].

PMID- 15431438
TI  - [Skin leishmaniasis in Azerbaidzhan].

PMID- 15431439
TI  - [Chronic ulcerative-vegetative pyoderma].

PMID- 15431440
TI  - [Correlation between tuberculosis and lupus erythematosus of the nose].

PMID- 15431441
TI  - [Therapeutic importance of vitamin B1 in treatment of eczema and other
      dermatoses].

PMID- 15431442
TI  - [Treatment of acute eczema and dermatitis with concentrated vitamin C from green
      walnuts].

PMID- 15431443
TI  - [Treatment of itch with sulfur powder].

PMID- 15431444
TI  - [Treatment of lupus erythematosus with transfusion of dry blood serum].

PMID- 15431446
TI  - [Treatment of onychomycosis].

PMID- 15431445
TI  - [New therapeutic in treatment of lymphogranulomatosis unguinale].

PMID- 15431447
TI  - [A case of neurofibromatosis with 9242 tumors].

PMID- 15431448
TI  - [Treatment of pointed condylomas].

PMID- 15431449
TI  - [Substitute for fir balsam].

PMID- 15431450
TI  - [Rational bandaging in hydradenitis].

PMID- 15431451
TI  - The treatment of retained fetal membranes and their sequelae in the bovine.

PMID- 15431452
TI  - Heartworms.

PMID- 15431453
TI  - Some new factors affecting the nutrition of farm animals.

PMID- 15431454
TI  - Infectious diseases of young pigs.

PMID- 15431455
TI  - Differential diagnosis of troublesome sheep diseases.

PMID- 15431456
TI  - Sulfonamides in poultry diseases.

PMID- 15431458
TI  - Dispensing in swine practice.

PMID- 15431457
TI  - A practitioner treats mastitis.

PMID- 15431459
TI  - Sutures and suture materials.

PMID- 15431460
TI  - Control of body and breath odors with chlorophyll fractions.

PMID- 15431461
TI  - Hospital management.

PMID- 15431462
TI  - Serum levels of horses following intramuscular injection of aqueous suspension of
      procaine penicillin.

PMID- 15431463
TI  - VETERINARIANS' role in public health.

PMID- 15431464
TI  - Aureomycin, an introduction to its pharmacology and activity.

PMID- 15431465
TI  - Occurrence of the ear mite, Raillietia auris (Leidy, 1872), of cattle in
      Colorado.

PMID- 15431466
TI  - Further studies on in vitro cultivated pneumoencephalitis (Newcastle disease)
      virus and its use as a vaccine.

PMID- 15431467
TI  - Some clinical uses of a new antihistamine.

PMID- 15431468
TI  - Aureomycin: its topical use in dermatitis in dogs.

PMID- 15431469
TI  - The effect of varying levels of thyroidal stimulation on adrenals under different
      environmental temperatures.

PMID- 15431470
TI  - Systematic treatment and control of streptococcic mastitis.

PMID- 15431471
TI  - Tattoo application to the ear of cattle.

PMID- 15431472
TI  - Urinary calculi in an aged bull.

PMID- 15431473
TI  - Feline practice.

PMID- 15431474
TI  - Occurrence of and treatment for the destruction of the African blue louse on
      sheep in northern Arizona.

PMID- 15431475
TI  - The effect of therapeutic and small daily doses of phenothiazine on the color of
      goat milk.

PMID- 15431476
TI  - Immunization of chicks hatched from hens immunized against Newcastle disease.

PMID- 15431478
TI  - Deficiency diseases in domestic animals.

PMID- 15431477
TI  - The efficacy of lead arsenate for the common tapeworm of sheep.

PMID- 15431479
TI  - Some aspects of the meat industry's contribution to science.

PMID- 15431480
TI  - Atypical pneumonia in a chimpanzee treated with chloromycetin.

PMID- 15431481
TI  - Obstructed cheek-pouch in a monkey.

PMID- 15431482
TI  - NOTE on the technique of intravenous injection in monkeys.

PMID- 15431483
TI  - A comparison of the immunity produced in cattle by the inoculation of Br. abortus
      strain 19 intradermally, intracaudally and subcutaneously.

PMID- 15431484
TI  - Bone and joint injuries in the dog.

PMID- 15431485
TI  - Cattle mange.

PMID- 15431486
TI  - Studies in the toxicity of benzene hexachloride.

PMID- 15431487
TI  - Carbon tetrachloride dosage in sheep; some observations on possible chronic
      toxicity.

PMID- 15431488
TI  - A comparison of the efficacy of sulphamezathine (sulphadimethyl-pyrimidine) and
      sulphaquinoxaline in the control of experimentally induced caecal coccidiosis in
      chicks.

PMID- 15431489
TI  - Notes on deaths in young piglets similar to the haemolytic disease in young
      foals.

PMID- 15431490
TI  - Artificial insemination of cattle; a review of the work of the Reading Cattle
      Breeding Centre, October 1st, 1944, to September 30th, 1948.

PMID- 15431491
TI  - Leptospirosis; clinical appearance of the dog with disease caused by Leptospira
      canicola with brief reference to diagnosis.

PMID- 15431492
TI  - The technique of exchange transfusion in the newborn foal.

PMID- 15431493
TI  - Sodium fluoride: a discussion of its use in the treatment of ascariasis in pigs.

PMID- 15431494
TI  - Fatal ingestion of tintacks by chimpanzee.

PMID- 15431495
TI  - Pigs and pig production.

PMID- 15431496
TI  - The attempted treatment of the leukosis complex by intraperitoneal injection of
      potassium iodide.

PMID- 15431497
TI  - A battery handle and adaptor for the Coldlite bovine vaginascope.

PMID- 15431498
TI  - Some observations on Johne's disease.

PMID- 15431499
TI  - A further note on the examination of faecal samples.

PMID- 15431500
TI  - Johne's disease in cattle.

PMID- 15431501
TI  - Vibrio foetus and infertility in cattle.

PMID- 15431503
TI  - MODERN advances in wound treatment; discussion by the Central Veterinary Society.

PMID- 15431502
TI  - The occurrence of S. typhimurium in hen eggs and its implications.

PMID- 15431504
TI  - Equine pregnancy diagnosis.

PMID- 15431505
TI  - The use of amprotropine (Bayer's brand of hexamine camphorate) in the treatment
      of hard-pad disease in dogs.

PMID- 15431507
TI  - The veterinary control of products of animal origin.

PMID- 15431506
TI  - Tick-borne fever as a cause of abortion in sheep.

PMID- 15431508
TI  - Castor bean poisoning.

PMID- 15431509
TI  - Bovine cysticercosis in Great Britain; some cases and comments.

PMID- 15431510
TI  - Some notes on the management of bulls in relation to semen production; based on
      observation and experiments made at the Ruthin Cattle Breeding Centre.

PMID- 15431511
TI  - The collection of early veterinary works in the Wellcome Historical Medical
      Library.

PMID- 15431512
TI  - A case of bowel resection in the dog.

PMID- 15431513
TI  - HUMAN health and the eradication of tuberculosis.

PMID- 15431514
TI  - NATIONAL Veterinary Medical Association of Great Britain and Ireland; report of
      Sub-Committee on Disposal of Animal Carcases.

PMID- 15431515
TI  - Fertility of bull, and artificial insemination.

PMID- 15431516
TI  - Beta-naphthoxyethanol suspensions ("anavenol"): a short-acting anesthetic for the
      horse.

PMID- 15431517
TI  - An improved form of "anavenol": "anavenol"-K--the combination of beta
      naphtoxyethanol with thialbarbituric ("kemithal") acid.

PMID- 15431518
TI  - A mixture of beta-naphthoxyethanol with thialbarbitone ("anavenol"-K) as an
      anaesthetic in farm animals.

PMID- 15431519
TI  - Treatment of bovine acetonaemia by the subcutaneous injection of magnesium
      sulphate; results of 4 cases investigated by the Department of Medicine, Royal
      Veterinary College.

PMID- 15431520
TI  - [Dr. Francisco Rodriguez Cartaya 1887-1948].

PMID- 15431521
TI  - [Second Panamerican Congress of Otolaryngology and Bronchoesophagology].

PMID- 15431522
TI  - [Temporary and permanent surgical collapsotherapy in pulmonary tuberculosis].

PMID- 15431523
TI  - [Rare postoperative complication of a cesarean section].

PMID- 15431524
TI  - [Applications of the determination of urinary steroid hormones in endocrinology].

PMID- 15431525
TI  - [Arterial hypertension; clinical forms, treatment].

PMID- 15431526
TI  - [A recent advance in cardiac therapy].

PMID- 15431527
TI  - [Treatment of Addison's disease].

PMID- 15431528
TI  - [Hydro-mineral and climate treatment of psoriasis at Molitg-les-Bains].

PMID- 15431529
TI  - [Not Available].

PMID- 15431530
TI  - [The Bulgarian cure in the treatment of Parkinson's disease].

PMID- 15431531
TI  - [Recent improvements of closed circuit anesthetic apparatus in France; new
      analgesic procedures].

PMID- 15431532
TI  - [Heredity and hereditary diseases in infantile neuropsychiatry].

PMID- 15431533
TI  - [Cellulitis and its treatment].

PMID- 15431534
TI  - [Treatment of adrenal insufficiency and Addison's disease].

PMID- 15431535
TI  - [Masculine sterility].

PMID- 15431536
TI  - [Urethritis].

PMID- 15431537
TI  - [Inositol, vitamin and growth factor].

PMID- 15431538
TI  - [Treatment of affections of rheumatic origin].

PMID- 15431539
TI  - [Structure of the neural periphery].

PMID- 15431540
TI  - [Necrotizing and ulcerating inflammations of the small intestine; so-called
      intestinal gangrene].

PMID- 15431541
TI  - [Fluorescent granulocytes (fluorocytes)].

PMID- 15431542
TI  - [Sequels of experimental intracardiac injection of small quantities of air in
      rabbits].

PMID- 15431543
TI  - [Acute pulmonary emphysema and interstitial emphysema in intracranial processes].

PMID- 15431544
TI  - [Histoenzymatic investigations of leukocyte granulations].

PMID- 15431545
TI  - [Pathological anatomy of tuberculosis in the kangaroo].

PMID- 15431546
TI  - [Topology of tumors].

PMID- 15431547
TI  - [Fluorochromization of living, preserved, and dead protoplasm with the basic
      acridine orange dye, and its relation to the metabolic activity of the cells].

PMID- 15431548
TI  - Hepatic amebiasis; difficulties in diagnosis.

PMID- 15431549
TI  - Medical-dental relations.

PMID- 15431550
TI  - The roentgen diagnosis of primary lung cancer.

PMID- 15431551
TI  - The management of primary glaucoma.

PMID- 15431552
TI  - The alcoholic problem.

PMID- 15431553
TI  - Pregnancy and heart disease.

PMID- 15431554
TI  - Clinicopathological reports; carcinoma of the ampulla of Vater with extensive
      metastasis to the liver.

PMID- 15431555
TI  - SIR Ronald Ross, (1857-1932).

PMID- 15431556
TI  - Progress and problems in national health.

PMID- 15431557
TI  - Milestones in public health.

PMID- 15431558
TI  - Hernia into the foramen of Winslow (report of a case).

PMID- 15431559
TI  - The pathologic physiology of benign prostatic hypertrophy.

PMID- 15431561
TI  - Conservative renal surgery.

PMID- 15431560
TI  - Barbiturate poisoning.

PMID- 15431562
TI  - Prognosis of schizophrenia.

PMID- 15431563
TI  - Without fear and trembling.

PMID- 15431564
TI  - Highlights of psychiatry: past, present, and the outlook for the future.

PMID- 15431565
TI  - 6-0 chromatized gut in wound closure after cataract extraction.

PMID- 15431566
TI  - Loeffler's syndrome; transitory pulmonary infiltrations and eosinophilia: case
      report.

PMID- 15431568
TI  - Adenocarcinoma of the corpus uteri; a clinicopathological study.

PMID- 15431567
TI  - Reconstructive procedures in plastic repair over bony surfaces.

PMID- 15431569
TI  - Fluid balance and electrolyte studies in toxemias of pregnancy.

PMID- 15431570
TI  - The values and methods of parental education.

PMID- 15431571
TI  - More liberalization of indications for therapeutic abortion and sterilization is
      in order.

PMID- 15431572
TI  - An integrated system of community blood banks in California; their roll in
      obstetrics and gynecology.

PMID- 15431573
TI  - Tracheoesophageal fistula due to external trauma; a report of a case and a review
      of the literature.

PMID- 15431574
TI  - A clinical observation of postpartum depression and its treatment.

PMID- 15431575
TI  - Metastatic tumors involving the central nervous system.

PMID- 15431576
TI  - Malignant tumors of the small intestine; a clinicopathologic analysis of 14
      cases.

PMID- 15431577
TI  - Rupture of the spleen with particular reference to delayed hemorrhage.

PMID- 15431578
TI  - Operative repair of sliding inguinal hernia.

PMID- 15431579
TI  - Prolapse of the uterus complicating pregnancy and labor.

PMID- 15431580
TI  - Advanced intraligamentary pregnancy; a review and case report.

PMID- 15431581
TI  - Twins with carcinoma of the cervix; a case report.

PMID- 15431582
TI  - The pressure-trol; a new safety device for use in uterotubal insufflation.

PMID- 15431583
TI  - Some new views of tumor genesis.

PMID- 15431584
TI  - Historical development of the second hormone of the testicle.

PMID- 15431585
TI  - [Local anesthesia (plexus and nerve block) in modern dentistry].

PMID- 15431586
TI  - [In memory].

PMID- 15431587
TI  - [Epigenesis and evolution].

PMID- 15431588
TI  - [The efficacy of natural and synthetic estrogens in peroral administration].

PMID- 15431589
TI  - [Photometric determination of urorrhodin].

PMID- 15431590
TI  - [Medical impressions of a trip to America].

PMID- 15431591
TI  - [Skeletal disease in infancy].

PMID- 15431592
TI  - [Value of palliative surgery in ovarian cancer].

PMID- 15431593
TI  - [Primary echinococcus of the spermatic cord].

PMID- 15431595
TI  - [Therapeutic use of pineal extracts].

PMID- 15431594
TI  - [Tuberculosis among the Croats 1943-5].

PMID- 15431596
TI  - [Medical impressions of a trip to America].

PMID- 15431597
TI  - [Cutaneous changes in systemic diseases].

PMID- 15431598
TI  - [Diagnosis of uremia at autopsy].

PMID- 15431599
TI  - [Results of total palmar aponeurectomy in Dupuytren's contracture].

PMID- 15431600
TI  - [Insufficiency and defects of the hip joint].

PMID- 15431601
TI  - [Traumatic and posttraumatic modifications in the encephalogram].

PMID- 15431602
TI  - [Medical and nonmedical psychotherapy].

PMID- 15431603
TI  - [Adrenaline -- noradrenaline].

PMID- 15431604
TI  - [Dysplasia of the hip joint].

PMID- 15431605
TI  - [Penicillin therapy of acute parotitis].

PMID- 15431606
TI  - [Case report of syphilis of the stomach].

PMID- 15431607
TI  - [The rarely-observed injurious effect of anesthesia].

PMID- 15431608
TI  - [Five years of reconstruction at the Hygiene Institute of the University of
      Vienna].

PMID- 15431609
TI  - [Uses and dangers of chloramphenicol (chloromycetin) in the treatment of typhoid
      and paratyphoid].

PMID- 15431610
TI  - [Earl diagnosis and prognosis of gastric cancer].

PMID- 15431611
TI  - [Endometriosis of the bladder and the follicular hormone].

PMID- 15431612
TI  - [Forty cases of progressive peritonitis following perforation of the appendix,
      without fatality].

PMID- 15431613
TI  - [Bone bank of the Vienna Emergency Hospital].

PMID- 15431614
TI  - [Observations and investigations on chronic enteritis in physical laborers].

PMID- 15431615
TI  - [Treatment of tuberculosis with thiosemicarbazones].

PMID- 15431616
TI  - [Vagotonic pseudo-ulcerous antropylorobulbitis; treatment of obstinate forms with
      bilateral subdiaphragmatic vagotomy].

PMID- 15431617
TI  - [Benign osteoarticular tuberculosis in the aged].

PMID- 15431618
TI  - [More logic in the prescription of thiouracil preparations].

PMID- 15431619
TI  - [Treatment of poliomyelitic paralyses].

PMID- 15431620
TI  - [Prevention and treatment of hemolytic disease of the newborn during pregnancy
      and birth].

PMID- 15431621
TI  - [M-factor antibodies in a pregnant woman].

PMID- 15431622
TI  - [Dupuytren's contracture].

PMID- 15431623
TI  - [General predisposition to cancer and its relation to cancerous disease].

PMID- 15431624
TI  - [Myocain E as an expectorant in pediatrics].

PMID- 15431625
TI  - [Experience with Alpine's salicylamide].

PMID- 15431626
TI  - [Indirect roentgen radiation in arthritis, neuralgia and other forms of pain].

PMID- 15431627
TI  - [Contact radiation of subcutaneous tumors].

PMID- 15431628
TI  - [Functional disorders of gastric motility in peptic ulcer].

PMID- 15431629
TI  - [Roentgenotherapy of bronchial asthma and related conditions].

PMID- 15431630
TI  - [Roentgenological topography of the heart, with special reference to the right
      cardiovascular angle].

PMID- 15431631
TI  - [Modifications in the nails in diseases of the joints].

PMID- 15431632
TI  - [Relation between old age and cancer].

PMID- 15431633
TI  - [New internal therapy of cancer metastases and of metastatic recurrences of
      cancer].

PMID- 15431634
TI  - [Metastasis of bronchial carcinoma, with reference to therapy].

PMID- 15431635
TI  - [Comments on Russe's article on serum reactions following tetanus antitoxin].

PMID- 15431636
TI  - [Basic principles in the hormone therapy of cancer].

PMID- 15431637
TI  - [Experience in insulin therapy; di-insulin novo].

PMID- 15431638
TI  - [Clinical experience with antistin, an antihistamine].

PMID- 15431639
TI  - [Clinical aspect and therapy of subacute bacterial endocarditis].

PMID- 15431640
TI  - [Water metabolism in acute parenchymous liver disease].

PMID- 15431641
TI  - [Effect of vitamin E on the metabolism of muscles treated with thyroxin].

PMID- 15431642
TI  - [Results of combined intravenous administration of magnesium and levosan].

PMID- 15431643
TI  - [The problem of heart measurement].

PMID- 15431644
TI  - [Recent advances in the theory of blood coagulation].

PMID- 15431645
TI  - [Reticulocyte metabolism].

PMID- 15431646
TI  - [Treatment of extrapyramidal motor disturbances].

PMID- 15431647
TI  - [Observations on silicosis].

PMID- 15431648
TI  - The diagnosis and treatment of chronic occlusive disease of the peripheral
      arteries.

PMID- 15431649
TI  - Insulin and insulin mixtures.

PMID- 15431650
TI  - Hemorrhagic disturbances in childhood.

PMID- 15431651
TI  - Cancer of the face and oral cavities.

PMID- 15431652
TI  - The significance of radioisotopes to radiology.

PMID- 15431653
TI  - The physician and mental health.

PMID- 15431654
TI  - Paroxysmal ventricular tachycardia; report of a case.

PMID- 15431655
TI  - Cholera in Wisconsin, 1832-1834.

PMID- 15431656
TI  - SIMPLE diagnostic gelatin liquefaction test for stool trypsin in fibrocystic
      disease of the pancreas.

PMID- 15431657
TI  - Diseases of adaptation.

PMID- 15431658
TI  - Industry looks at the doctor.

PMID- 15431659
TI  - The Rh factor in pediatrics.

PMID- 15431660
TI  - Beta ray uses in ophthalmology.

PMID- 15431661
TI  - Roentgen therapy of cavernous hemangiomas; report of a case complicated by
      secondary infection.

PMID- 15431662
TI  - Some practical considerations in the problem of carcinoma of the rectum and lower
      sigmoid colon.

PMID- 15431664
TI  - Vertigo; differential diagnosis and treatment.

PMID- 15431663
TI  - The use of fluorides in the prevention of dental caries.

PMID- 15431665
TI  - The coagulation mechanism.

PMID- 15431666
TI  - Clinical use of antihistamines.

PMID- 15431667
TI  - Some problems in the care of newborn infants.

PMID- 15431668
TI  - Neoplasms of the blood and blood-forming organs.

PMID- 15431669
TI  - Emotional problems of children.

PMID- 15431671
TI  - Incidence of gastric and duodenal ulcers.

PMID- 15431670
TI  - Emotional problems in children, with emphasis on implications in medical
      practice.

PMID- 15431672
TI  - Practical aspects of anticoagulant therapy.

PMID- 15431673
TI  - Complications of pregnancy.

PMID- 15431674
TI  - A critical appraisal of the present status of "Rh hapten".

PMID- 15431675
TI  - Dr. Winternitz as Dean of the School of Medicine.

PMID- 15431676
TI  - Prefrontal lobes and social development.

PMID- 15431677
TI  - Commentary on typhus control in World War II.

PMID- 15431678
TI  - Clinical observations on terramycin.

PMID- 15431679
TI  - Some reminiscences of the "pathological" in the early days of the Johns Hopkins
      Hospital and Medical School.

PMID- 15431680
TI  - The giant-cells of measles.

PMID- 15431681
TI  - Interstitial desoxyribonucleic acid following cell death.

PMID- 15431682
TI  - The morphology and staining characteristics of the Treponema pallidum. Review of
      the literature and description of a new technique for staining the organism in
      tissues.

PMID- 15431683
TI  - Certain aspects of acute infection of the respiratory tract.

PMID- 15431684
TI  - The significance of the non-neoplastic lesions induced in the central nervous
      system of ducklings by the virus of a duck variant of the Rous sarcoma.

PMID- 15431685
TI  - Post-mortem pulmonary edema.

PMID- 15431686
TI  - Reminiscences of an erstwhile student.

PMID- 15431687
TI  - Milton Charles Winternitz.

PMID- 15431688
TI  - The relation of herpes virus to the cell nucleus.

PMID- 15431689
TI  - Some notes on the Yale University School of Medicine with special reference to
      Milton Winternitz.

PMID- 15431690
TI  - Various aspects of adolescence.

PMID- 15431691
TI  - An attempt to interpret a great scientist's contribution to humanity through
      medicine and nursing.

PMID- 15431692
TI  - The heterologous transplantation of human melanomas.

PMID- 15431693
TI  - The non-university teaching hospital and postgraduate medical education.

PMID- 15431694
TI  - The genesis and functional implications of collateral circulation of the lungs.

PMID- 15431695
TI  - Vascular lesions in the dog following thyroidectomy and viosterol feeding.

PMID- 15431696
TI  - The isolation of brucella organisms from apparently healthy individuals.

PMID- 15431697
TI  - The problem of the lipoid thromboplastins.

PMID- 15431698
TI  - Personal observations.

PMID- 15431699
TI  - Acute traumatic subdural hygroma.

PMID- 15431700
TI  - The influence of adrenal and pituitary hormones on liver arginase activity
      following nephrectomy or renal pedicle ligation in the rat.

PMID- 15431701
TI  - Social and geographical pathology.

PMID- 15431702
TI  - Dr. Winternitz and pediatrics at Yale.

PMID- 15431703
TI  - Psychiatry at Yale in the academic year of 1925-26.

PMID- 15431704
TI  - A disciple of Hugh Quoil tarries briefly in New Haven.

PMID- 15431705
TI  - A challenging leader.

PMID- 15431707
TI  - The infertility problem; a commentary and review of 3 years, clinic experience.

PMID- 15431706
TI  - The use of blood volume studies as a clinical aid in intravenous therapy.

PMID- 15431708
TI  - Circulatory factors in the pathogenesis of experimental arteriolar necrosis.

PMID- 15431709
TI  - A memorandum on "Winter" at the Hopkins.

PMID- 15431710
TI  - "Winter" at Yale.

PMID- 15431711
TI  - Comments upon the medical curriculum; excerpts from reports to the President and
      Fellows of Yale University.

PMID- 15431712
TI  - [Penicillin and its use in dental, oral and maxillary surgery].

PMID- 15431713
TI  - [Experiences with local application of sulfonamides and vitamin C in ulcerating
      stomatitis].

PMID- 15431714
TI  - [Important data in cancer research].

PMID- 15431715
TI  - [Semantic confusion concerning the concepts of light and dark in roentgenological
      diagnosis].

PMID- 15431716
TI  - [Care of the teeth and mouth as a scientific part of dentistry].

PMID- 15431717
TI  - [Dental drugs from the Compositae].

PMID- 15431718
TI  - [Rapid treatment and focal formation].

PMID- 15431719
TI  - [Significance and scope of the Zentralblatt].

PMID- 15431720
TI  - [Treatment of acute diseases of the roots].

PMID- 15431721
TI  - [Filling or draining of the root canal].

PMID- 15431722
TI  - [Thoughts on psychosomatics].

PMID- 15431723
TI  - [Drugs from the Rosa in dentistry].

PMID- 15431724
TI  - [Penicillin in dental, oral and maxillary surgery].

PMID- 15431725
TI  - [Root filling or draining].

PMID- 15431726
TI  - [Effect of sunflower-seed meal upon the hard dental tissues].

PMID- 15431727
TI  - [New orthodontic therapy: treatment of an open sucking bite with Tegtmeier's
      impulsator].

PMID- 15431728
TI  - [Effect of carbohydrate and protein in the diet upon caries, gingivitis,
      parodontosis and wound healing].

PMID- 15431729
TI  - [Dental hygiene at the beginning of the nineteenth century].

PMID- 15431730
TI  - [The defensor-splint, a boxer's mouthpiece, and its preparation].

PMID- 15431732
TI  - [Dentistry on new paths].

PMID- 15431731
TI  - [Final word in the discussion, "We're daily poisoning ourselves"].

PMID- 15431733
TI  - [New hemostatic].

PMID- 15431735
TI  - [Antisepton Ganslmayer 800 and 600 as a test and remedy in focal infection].

PMID- 15431734
TI  - [Adjuvant peroral analgesia].

PMID- 15431736
TI  - [Full prosthesis].

PMID- 15431737
TI  - [Abutments and pontics].

PMID- 15431738
TI  - [Lower prosthesis with subglossal wings].

PMID- 15431739
TI  - [Experience with LPC pyocid and LPC paradentosis paste].

PMID- 15431740
TI  - [Conservative therapy and the problem of odontogenous focal infection].

PMID- 15431741
TI  - [Odontogenous focal infection in children].

PMID- 15431742
TI  - [Clinical use of electrocardiography in cardiac lesions resulting from focal
      infection].

PMID- 15431743
TI  - [Another viewpoint in focal infection].

PMID- 15431744
TI  - [Treatment of odontogenous focal infections].

PMID- 15431745
TI  - [Prosthetic planning and focal infection].

PMID- 15431746
TI  - [Tests for focal infection].

PMID- 15431748
TI  - [Sterilization of hand and engine pieces].

PMID- 15431747
TI  - [Pathway of focal infection].

PMID- 15431749
TI  - [Surgical guards for hand pieces].

PMID- 15431750
TI  - [Biochemistry of fluorine in relation to caries].

PMID- 15431751
TI  - [Unusual formation of non-dentigerous cyst in the lower jaw].

PMID- 15431752
TI  - [Unusual acquired palatal defect].

PMID- 15431753
TI  - [Indication and contraindications for suprarenin, corbasil and meropitan].

PMID- 15431754
TI  - [Twenty-five years of gingival-margin incision in apicoectomy].

PMID- 15431755
TI  - [Dr. Spinner's medicaments].

PMID- 15431756
TI  - [Production of synthetics, especially of tridermalith and pitri].

PMID- 15431757
TI  - [Injection anesthesia of inflamed tissue].

PMID- 15431758
TI  - [Investigations on gothic palate in school and industry].

PMID- 15431759
TI  - [Treatment of overbite with bite plates].

PMID- 15431760
TI  - [Functional maxillary orthopedics not a special science].

PMID- 15431761
TI  - [New methods of treatment in maxillary orthopedics].

PMID- 15431762
TI  - [Health services in Slovakia following decentralization].

PMID- 15431763
TI  - [Public health personnel in Slovakia].

PMID- 15431764
TI  - [Problem of child mortality in Slovakia].

PMID- 15431765
TI  - [Health education in Slovakia].

PMID- 15431766
TI  - [Epidemiologic problems in Slovakia].

PMID- 15431767
TI  - [Plan for the public health services for 1950].

PMID- 15431768
TI  - [Legislation on keeping of physician's records].

PMID- 15431769
TI  - [Sick insurance].

PMID- 15431770
TI  - [Legislation concerning obstetric services].

PMID- 15431771
TI  - [Public health in the region of Poprad].

PMID- 15431772
TI  - [Epidemiologic problems in Slovakia].

PMID- 15431773
TI  - [Medical services in the factory Merina].

PMID- 15431774
TI  - [The duration of human pregnancy].

PMID- 15431775
TI  - [Injuries of the pelvic symphyses during pregnancy and birth].

PMID- 15431776
TI  - [Kielland's forceps and levator-tractor].

PMID- 15431777
TI  - [Obstetrical implications of cleidocranial dysostosis].

PMID- 15431778
TI  - [Psychic and vegetative-nervous influences on lactation].

PMID- 15431779
TI  - [Bacteriological and morphological investigations of an abortion of a five-month
      fetus caused by subacute typhoid in the mother].

PMID- 15431780
TI  - [Observations on a diaplacental infection caused by acidophilic bacteria].

PMID- 15431781
TI  - [Pathogenesis of hyperinsulinism].

PMID- 15431782
TI  - [Acute experimental atophanyl gastritis].

PMID- 15431783
TI  - [Novocain therapy of bronchial asthma].

PMID- 15431784
TI  - [Typhoid fever in an infant with clinical aspect of acute paramyeloblastic
      leukemia].

PMID- 15431785
TI  - [Structure and pathogenesis of depression states, with observations of the
      medical significance of hypochondria].

PMID- 15431786
TI  - [Practical determination of penicillin resistance].

PMID- 15431787
TI  - [Endocarditis lenta and protein lability tests].

PMID- 15431788
TI  - [Origin of the monophasic current; investigations in electrocardiographic
      theory].

PMID- 15431789
TI  - [Investigations on the effect of penicillin upon the valvular pathogens of
      endocarditis lenta].

PMID- 15431790
TI  - [Effect of typhoid fever upon gastric function].

PMID- 15431791
TI  - [Central scotoma in disorders of metabolism].

PMID- 15431792
TI  - [Wendt's massive-dose vitamin therapy].

PMID- 15431793
TI  - [Clinical manifestation of the Sanarelli-Shwartzman phenomenon in dermatology. I.
      Herpes zoster generalisatus and the Sanarelli-Shwartzman phenomenon].

PMID- 15431794
TI  - [Psoriasis and pyoderma].

PMID- 15431795
TI  - [Clinical observations on H. Weiss's article, "A case of anaphylactic edema
      following intramuscular injection of bismuth, etc."].

PMID- 15431796
TI  - [Reply to V. Lundt's observations].

PMID- 15431797
TI  - [The effect of dinitro-ortho-cresol upon the skin and upon the organism].

PMID- 15431798
TI  - [Onychographosis].

PMID- 15431799
TI  - [Questionnaire: Pruritus (Part I)].

PMID- 15431800
TI  - [Hematogenic infectious hepatitis and its prevention].

PMID- 15431801
TI  - [Leprosy infection].

PMID- 15431802
TI  - [Fox-Fordyce disease without pruritus].

PMID- 15431803
TI  - [Hyperkeratosis in the region of the nipple and areola].

PMID- 15431804
TI  - [Investigation on the biological effects of serumlact in inflammatory
      dermatoses].

PMID- 15431805
TI  - [Differential diagnostic difficulties during syphilis therapy].

PMID- 15431806
TI  - [Madura foot].

PMID- 15431807
TI  - [Extensive pilose nevus].

PMID- 15431808
TI  - [Sources of venereal infections in Danish internment camps].

PMID- 15431809
TI  - [Pruritus].

PMID- 15431810
TI  - [Casuistics of localized erythrokeratoderma].

PMID- 15431811
TI  - [Side effects of TB-1 therapy especially on the nervous system].

PMID- 15431812
TI  - [Norwegian or crusted scabies in a mongoloid idiot].

PMID- 15431813
TI  - [Herxheimer reaction in penicillin-treated syphilis].

PMID- 15431814
TI  - [Changes in our therapeutic thinking].

PMID- 15431815
TI  - [Toxic melanodermatitis (illustration)].

PMID- 15431816
TI  - [Tuberculosis cutis luposa (illustration)].

PMID- 15431817
TI  - [Erysipelas carcinomatosum following amputation of the breast].

PMID- 15431818
TI  - [Hereditary epidermolysis bullosa dystrophica (illustration)].

PMID- 15431819
TI  - [Total gangrene of the scrotum following injury].

PMID- 15431820
TI  - [Relation between pyrifer and paroxysmal hemoglobinuria; contribution to the
      pathogenesis of paroxysmal hemoglobinuria].

PMID- 15431821
TI  - [Sexuality in aging men].

PMID- 15431822
TI  - [Pruritus].

PMID- 15431823
TI  - [Recent methods of treatment of furuncle, carbuncle and sweat gland abscesses].

PMID- 15431824
TI  - [So-called salvarsan hepatitis and salvarsan encephalitis].

PMID- 15431825
TI  - [Penicillin therapy of early syphilis in a hemophiliac].

PMID- 15431826
TI  - [Erythematodes exacerbated by old salvarsan and cured by uliron].

PMID- 15431827
TI  - [Gynecomastia as a side effect of urethane therapy].

PMID- 15431828
TI  - [Problems in the campaign against venereal disease].

PMID- 15431829
TI  - [Problem of vagrants].

PMID- 15431830
TI  - [Observations on a typhoid epidemic].

PMID- 15431831
TI  - [Visualization of bacteriophage adsorption with the electron microscope].

PMID- 15431832
TI  - [Investigations in the variability of biochemical characteristics in
      streptococci].

PMID- 15431833
TI  - [Significance of resistance determination of pathogenic microorganisms in vitro
      and its evaluation for therapeutic practice].

PMID- 15431834
TI  - [Effect of honey upon the growth of tubercle bacilli].

PMID- 15431835
TI  - [Experimental transformation of the typhoid bacillus in to paratyphoid B
      bacillus].

PMID- 15431836
TI  - [Identity and classification of Roelck's Bacillus paradysenteriae palatinense
      (Roelcke)].

PMID- 15431837
TI  - [Increasing the toxin production of aerogenic bacteria by culture and
      inoculation].

PMID- 15431838
TI  - [Significance of preliminary cultures for the toxin production of aerogenic
      bacteria in synthetic media].

PMID- 15431839
TI  - [Statistical investigations in bacteriophagic lysis].

PMID- 15431840
TI  - [Chromosome modification caused by injection of active substances into the buds
      of Paeonia tenuifolia].

PMID- 15431841
TI  - [Dominance changes in Oenothera as a problem in genetics and developmental
      physiology].

PMID- 15431842
TI  - [An analysis of mutations produced in Drosophila by ethylurethane].

PMID- 15431843
TI  - [Supplementary findings on the mutagenic effect of urethane (the ester of
      carbamic acid) in Drosophila].

PMID- 15431844
TI  - [Congenital intestinal occlusion in the newborn].

PMID- 15431845
TI  - [Evaluation of the Morawitz-Jurgens capillarothrombometer].

PMID- 15431846
TI  - [Pathology of hereditary thrombasthenia].

PMID- 15431847
TI  - [Recent investigations on the origin of B. bifidus..].

PMID- 15431848
TI  - [Necrotizing enteritis in infant and child].

PMID- 15431849
TI  - [Comparative examination of the bactericidal properties of gastroduodenal juice
      against coli bacilli in infants with and without intestinal affections].

PMID- 15431850
TI  - [Effect of blood histaminase and serum-cholinesterase in toxic states in
      children].

PMID- 15431851
TI  - [Streptomycin therapy of tuberculous meningitis].

PMID- 15431852
TI  - [Streptomycin therapy of tuberculous meningitis; symptomatology].

PMID- 15431853
TI  - [New method of recording changes in volume of the human heart].

PMID- 15431854
TI  - [Edematous circulatory decompensation and protein deficiency].

PMID- 15431855
TI  - [Effect of anemia upon the specific tonus of the voluntarily relaxed muscles].

PMID- 15431856
TI  - [Pathogenesis and therapy of angioneuropathy].

PMID- 15431857
TI  - [Experiments with a biological model in reproducing conditions which lead to axis
      deviation in the electrocardiogram of the hypertrophic heart].

PMID- 15431858
TI  - [Effect of arterenol infusions upon circulation in normal- and hypertonic
      states].

PMID- 15431859
TI  - [Observations on pre-excitation; the Wolff-Parkinson-White syndrome and related
      electrocardiographic types].

PMID- 15431860
TI  - [Effect of modifications of intrathoracic pressure upon hemodynamics].

PMID- 15431861
TI  - [Treatment of spontaneous obstruction of the cranial sinuses].

PMID- 15431862
TI  - [Effect of histamine on the inferior turbinated bone in man].

PMID- 15431863
TI  - [Motor aphasia and agraphia in rhinogenous cerebral abscess].

PMID- 15431864
TI  - [Relations of the nasal sinuses to the orbit and the optic nerve].

PMID- 15431865
TI  - [Objective tinnitus and its cause].

PMID- 15431866
TI  - [Objective tinnitus and its cause].

PMID- 15431867
TI  - [Treatment of senile deafness with vitamin A].

PMID- 15431868
TI  - [Treatment of senile deafness with vitamin A].

PMID- 15431869
TI  - [Surgical therapy of maxillary neuralgia].

PMID- 15431870
TI  - [A new plastic esophagotracheoscope].

PMID- 15431871
TI  - [Origin of the moistness of the mucosal surfaces of the upper air passages].

PMID- 15431872
TI  - [Phlegmonous processes within the depth of the cranial bones, followed by
      endocranial complications].

PMID- 15431873
TI  - [Attempt at clarification of the so-called regression phenomenon (recruitment)].

PMID- 15431874
TI  - [Laryngeal tuberculosis and TB1].

PMID- 15431875
TI  - [Fatalities in local anesthesia tonsillectomies].

PMID- 15431876
TI  - [Experience with scophedal, especially in pediatrics].

PMID- 15431877
TI  - [Roentgenology of the small wings of the sphenoid bone].

PMID- 15431878
TI  - [Conduction anesthesia in maxillary surgery].

PMID- 15431879
TI  - [Problem of granuloma gangraenescens].

PMID- 15431880
TI  - [Prof. Julius Hegener on his eightieth birthday].

PMID- 15431881
TI  - [Impressions of a trip for purpose of study in the U.S.A..].

PMID- 15431882
TI  - [Total, bound and free tryptophan content of food; contribution to formulation of
      the amino acid balance].

PMID- 15431883
TI  - [Glue content of meat, meat products and sausages].

PMID- 15431884
TI  - [Protein catabolism in germinant leguminous plants and its significance in
      nutrition physiology].

PMID- 15431885
TI  - [Buffer capacity of the flesh of fish in relation to hydrochloric acid as a test
      of freshness].

PMID- 15431886
TI  - [Variations in extraneous water content of identically prepared sausages].

PMID- 15431887
TI  - [Soybean protein in human nutrition; review of recent American work].

PMID- 15431888
TI  - [Paul Schulze].

PMID- 15431889
TI  - [Microsporidia in the larvae of Chaoborus Lichtenstein (Culicidae)].

PMID- 15431890
TI  - [Amblyomma diemeniae, a new reptilian tick from Australia, with observations on
      variant formations of the clava in the genus Amblyomma].

PMID- 15431891
TI  - [Biology and morphology of the pathogen of the parasitic leaf blight of the
      poppy].

PMID- 15431892
TI  - [Alternation of generations in the parasitic Tachyblaston ephelotensis Martin
      (Suctoria)].

PMID- 15431893
TI  - [Studies of the intestinal flagellates of termites; Joenia annectens Grassi in
      Calotermes flavicollis Fabr].

PMID- 15431894
TI  - [Observations on Felty's syndrome].

PMID- 15431895
TI  - [Parenteral novalgin therapy of rheumatic fever with special reference to
      carditis].

PMID- 15431896
TI  - [Rheumatism and the nervous system; meningeal reactions in rheumatism; clinical
      aspects].

PMID- 15431897
TI  - [Wilhelm Schuffner].

PMID- 15431898
TI  - [Fate of bacteria lodged on the mucous membranes; studies in phagocytosis].

PMID- 15431899
TI  - [Studies in microorganic structure; inorganic inclusions of bacterial cells].

PMID- 15431900
TI  - [Serodiagnosis of the Vi agglutinin].

PMID- 15431901
TI  - [Studies in the effect of sulfonamides; sulfonamide therapy of injectious and
      toxic enteritis].

PMID- 15431902
TI  - [Studies in staining of polar bodies].

PMID- 15431903
TI  - [Filtration as a method of concentrating tubercle bacilli for bacterioscopic
      examination].

PMID- 15431904
TI  - [The yeast extract vitam-bakt as a substitute for meat in the preparation of
      culture media].

PMID- 15431905
TI  - [Double- and triple-bodied flasks for sterilization tests].

PMID- 15431906
TI  - [Correction to P. Dahr's article on blood-group research].

PMID- 15431907
TI  - [Retrograde oxyuriasis].

PMID- 15431908
TI  - [New method of counting ova in sewage and feces].

PMID- 15431909
TI  - [Significance of the weather in the epidemiology of contagious disease].

PMID- 15431910
TI  - [Microbiology and meteorology].

PMID- 15431911
TI  - [Effect of biotropic weather fronts upon general resistance and specific immunity
      to diphtheria].

PMID- 15431912
TI  - [Epidemiology of virus influenza and virus pneumonia (Q fever)].

PMID- 15431913
TI  - [Epidemiology of leptospirosis].

PMID- 15431914
TI  - [Typhoid-paratyphoid epidemics due to contaminated milk, and their prevention].

PMID- 15431915
TI  - [Epidemiologic findings in cases of horse meat poisoning].

PMID- 15431916
TI  - [Two new epidemiologic concepts, aggressivity and congressivity].

PMID- 15431917
TI  - [Effect of vaccination during the incubation period of typhoid fever].

PMID- 15431918
TI  - [Epidemiologic and bacteriologic observations on a large village].

PMID- 15431919
TI  - [Hygiene of water supply].

PMID- 15431920
TI  - [Equipment and operation of large water works].

PMID- 15431921
TI  - [Rural water supply].

PMID- 15431922
TI  - [Drinking water supply in schools].

PMID- 15431923
TI  - [Bacteriology and serology of the so-called acne bacillus, Bacterium renale
      cuniculi Manteufel et Herzberg; acne bacillus as airborne a dangerous source of
      error in bacterioserologic technic].

PMID- 15431924
TI  - [Infiltration depth of ascarid ova during seepage of sewage into soil].

PMID- 15431925
TI  - [Verminosis and agricultural use of waste water].

PMID- 15431926
TI  - [Disposal of municipal sewage].

PMID- 15431927
TI  - [Present status of sewage disposal].

PMID- 15431929
TI  - [Peridural anesthesia].

PMID- 15431928
TI  - [Application of curarin in treatment and combined curarin-narcotic anesthesia].

PMID- 15431930
TI  - [Experience with peridural anesthesia].

PMID- 15431931
TI  - [Report on over 1000 peridural anesthesias in gynecological operations].

PMID- 15431932
TI  - [Does peridural anesthesia imply a progress in operative gynecology?].

PMID- 15431933
TI  - [Determination of blood circulation before peridural anesthesia by means of the
      cold pressor test].

PMID- 15431934
TI  - [Lumbar anesthesia with preliminary treatment with SEE].

PMID- 15431935
TI  - [Gynecology and Coffey-Mayo operation].

PMID- 15431936
TI  - [Ureter implantation].

PMID- 15431937
TI  - [Development of ureteral fistula following Wertheim's operation].

PMID- 15431939
TI  - [Results with pyramidal fasciaplasty].

PMID- 15431938
TI  - [Recent view-points on fasciaplasty].

PMID- 15431940
TI  - [The round ligament span in treatment of prolapse].

PMID- 15431941
TI  - [Perforation of the uterus with injury of the bladder during curettage for
      climacteric hemorrhage].

PMID- 15431942
TI  - [Counteracting relative obstetric disparity by correction of the presentation].

PMID- 15431943
TI  - [Grave diabetes mellitus with multiple obstetric complications].

PMID- 15431944
TI  - [Experimental treatment of diabetes mellitus as a regulation disorder with sex
      hormone in depot form].

PMID- 15431946
TI  - [Hysterotomia vaginalis anterior through a curved incision of the isthmus].

PMID- 15431945
TI  - [Corpus luteum graviditatis and choriongonadotropin].

PMID- 15431947
TI  - [Supravaginal sectio vaginalis].

PMID- 15431948
TI  - [Bardenheuer's incision in operative treatment of mastitis].

PMID- 15431949
TI  - [Effect of prostigmin in threatened abortion].

PMID- 15431950
TI  - [Roentgenological measurement of the length of the fetus].

PMID- 15431951
TI  - [Congenital skin defects and their origin].

PMID- 15431952
TI  - [Hypoplastic multiple defects of the joints].

PMID- 15431953
TI  - [Conjoined twins].

PMID- 15431954
TI  - [Concurrent anencephaly in uniovular twins].

PMID- 15431956
TI  - [The social indication].

PMID- 15431955
TI  - [Case of full term thoracopagus and diagnosis of malformations before birth].

PMID- 15431957
TI  - [Birth control; but what can we recommend?].

PMID- 15431958
TI  - [Experiences with a new pregnancy test with domestic Anura (frogs and toads)].

PMID- 15431959
TI  - [Application of pregnancy test with the domestic green water frog].

PMID- 15431960
TI  - [Pregnancy test with frogs].

PMID- 15431961
TI  - [Efficacy of placental substance and retroplacental serum in the tadpole test].

PMID- 15431962
TI  - [Has eclampsia decreased also in the last war (1939-1945)?].

PMID- 15431963
TI  - [Cause of cardiac and circulatory deaths in eclampsia].

PMID- 15431964
TI  - [Prolonged labor through the amnion].

PMID- 15431965
TI  - [Acute hydramnion; contribution to the genesis and prophylaxis of eclampsia].

PMID- 15431966
TI  - [Herpes gestationis occurring after the death of an extrauterine fetus].

PMID- 15431967
TI  - [Clinical aspect of pelipathia vegetativa].

PMID- 15431968
TI  - [Painless birth].

PMID- 15431969
TI  - [Observations on 2320 births with premature rupture of the amnion at term].

PMID- 15431970
TI  - [Expulsion of the decidua without abortion].

PMID- 15431971
TI  - [Perforation of the uterus by the lower extremity of the fetus followed by
      spontaneous birth].

PMID- 15431972
TI  - [Rare injury of a girl 12 years of age due to rape].

PMID- 15431973
TI  - [Case of asymptomatic postpartum thrombosis of the deep femoral veins followed by
      pulmonary embolism and death].

PMID- 15431974
TI  - [Attempt at misrepresentation of pregnancy duration].

PMID- 15431975
TI  - [Erroneous diagnosis of tubal rupture despite typical anamnesis and classical
      symptomatology].

PMID- 15431976
TI  - [Multiple cancer].

PMID- 15431977
TI  - [Large laparocele, recurrent ascites; T-drain left intentionally].

PMID- 15431978
TI  - [Tuberculosis and pregnancy].

PMID- 15431979
TI  - [Isolated tuberculosis of the cervical canal].

PMID- 15431980
TI  - [Occurrence and significance of Bacterium pyogenes anaerobium (Buday) in
      gynecology].

PMID- 15431981
TI  - [Choice of therapy determined by bacterial resistance].

PMID- 15431982
TI  - [Modifications of leukocyte nuclei in gonorrhea].

PMID- 15431983
TI  - [Isolation of gonococci during puerperium].

PMID- 15431984
TI  - [Unusual cause of suppurative parametritis following abortion].

PMID- 15431985
TI  - [Diaplacental infection of the fetus with poliomyelitis during the ninth month of
      pregnancy].

PMID- 15431986
TI  - [Spontaneous birth in acute anterior poliomyelitis].

PMID- 15431987
TI  - [Central vestibular lesions in mice poisoned by dichlorophenolarsinic acid].

PMID- 15431988
TI  - [Ultramicroscopic and phase contrast studies of placental spodograms].

PMID- 15431989
TI  - [4 Cases of pernicious anemia treated with vitamin B12].

PMID- 15431990
TI  - [Case of destructive mole in a peculiar phase of invasion; initial
      chorionepitheliomatous transformation].

PMID- 15431991
TI  - [Behavior of tuberculin allergy in subjects under subcutaneous oxygen therapy].

PMID- 15431992
TI  - [Severe emphysema, disseminated to the entire body due to tracheal injury].

PMID- 15431993
TI  - [Suppuration in succession of bilateral ovarian cysts in a pregnant woman
      convalescing from typhoid fever].

PMID- 15431994
TI  - [Morton's neuralgia].

PMID- 15431995
TI  - Bone-grafting of osteomized femur by os purum in the surgical reduction of
      congenital dislocation of the hip joint in children.

PMID- 15431997
TI  - [Organization of the service of orthopedic appliances in Czechoslovakia].

PMID- 15431996
TI  - [Enchodroma of the long bones].

PMID- 15431998
TI  - [Hallux varus and its therapy].

PMID- 15431999
TI  - Antero-lateral chordotomy in cases of painful arthritis of the hip joint.

PMID- 15432000
TI  - [Arthritis deformans of the hand in a hockey player].

PMID- 15432001
TI  - [Injuries according to data of UNP].

PMID- 15432002
TI  - [Radiologically negative cancer of the esophagus].

PMID- 15432003
TI  - [Indications for by-pass esophagogastroanastomosis].

PMID- 15432004
TI  - [Congenital atresia of the esophagus].

PMID- 15432005
TI  - [Indications and results of the surgical treatment of essential hypertension].

PMID- 15432006
TI  - [Total cystectomy].

PMID- 15432007
TI  - [Variations in the blood volume in surgery measured by radioactive phosphorus].

PMID- 15432008
TI  - [Late results of 200 gastrectomies].

PMID- 15432009
TI  - [Peptic ulcers and the Kocher-Pean operation].

PMID- 15432011
TI  - [Intravascular blood clots].

PMID- 15432010
TI  - [Application of radioactive isotopes to surgical diagnosis].

PMID- 15432012
TI  - [Test of resistance to heparin in surgical patients].

PMID- 15432013
TI  - [Dicumarol poisoning].

PMID- 15432014
TI  - [Method of plastic surgery of the trachea with autoplastic grafts of costal
      cartilage; experimental research].

PMID- 15432015
TI  - [Adaptation in tourniquet shock; pressure and thermal data].

PMID- 15432016
TI  - [Articular alterations in the knee after meniscectomy, with particular reference
      to arthritis deformans].

PMID- 15432018
TI  - [Topography of nerve roots and radicles].

PMID- 15432017
TI  - [Appendicular abscess perforated into the transverse colon].

PMID- 15432019
TI  - [Significance of the presence of Koch's bacillus in the cerebrospinal fluid].

PMID- 15432020
TI  - [Direct compatibility tests].

PMID- 15432021
TI  - [Cutaneous thermometry in the normal subject].

PMID- 15432022
TI  - [First cases of tularemia in Belgium].

PMID- 15432023
TI  - [Visualization of the pulmonary artery by accidental injection of lipiodol into
      the liver].

PMID- 15432024
TI  - [Recent medical acquisitions in Sweden and Denmark, particularly in the field of
      cardiovascular diseases].

PMID- 15432025
TI  - [Laboratory infection from Brucella abortus].

PMID- 15432026
TI  - [Postmortem diagnosis of botulism].

PMID- 15432027
TI  - [Case of meningeal spirochetosis].

PMID- 15432028
TI  - [Laboratory tests in salmonellosis treated with chloromycetin].

PMID- 15432029
TI  - [Evaluation of prothrombin level from the Quick correlation line].

PMID- 15432030
TI  - [Organic acids, sodium, iron, pH and the growth of Loeffler's bacillus].

PMID- 15432031
TI  - [New method of determining estrogenic hormones].

PMID- 15432032
TI  - [Technic of fractional determination of urinary 17-ketosteroids].

PMID- 15432033
TI  - [Cytology of effusions and expectorations in the diagnosis of neoplasms].

PMID- 15432034
TI  - [Relations of cholesterol in myxedema and in the hypercholesterinemia of treated
      Basedow's disease].

PMID- 15432035
TI  - [Determination of iodemia].

PMID- 15432036
TI  - The variability in the hyaluronic acid content of the dermal connective tissue
      under the influence of thyroid hormone; mast cells, the peripheral transmitters
      of hormonal action.

PMID- 15432037
TI  - Cutaneous absorption during the menstrual cycle and its influence on intradermal
      reactions of the delayed type.

PMID- 15432038
TI  - Results of some skin tests in various phases of the menstrual cycle, with special
      reference to the disappearance time of the injection wheal.

PMID- 15432039
TI  - On the topical treatment with penicillin and the concomitant hypersensitivity
      reactions.

PMID- 15432040
TI  - The action of penicillin on the gonococcus at temperatures above 37 degrees C.

PMID- 15432041
TI  - [Basic errors of present topical therapy].

PMID- 15432042
TI  - A case of erythroplasia Queyrat.

PMID- 15432043
TI  - Poikiloderma, myositis.

PMID- 15432044
TI  - A case of asthenia crurum dolorosa ("restless legs") with ulcus cruris.

PMID- 15432045
TI  - On the relation between penicillin dosage and non-relapse percentage for the 7
      1/2 days' cure of early syphilis; a statistical study based upon American
      publication.

PMID- 15432046
TI  - [Arrhenoblastoma of the ovary and its relation to genuine contracted kidney].

PMID- 15432047
TI  - Natural and synthetic oestrogenic substances; their relative effectiveness when
      administered orally.

PMID- 15432048
TI  - Quantitative determination of dehydroisoandrosterone; determination in pure
      solutions.

PMID- 15432049
TI  - The effect of intravenous administration of adrenaline and dl-nor-adrenaline on
      the circulating eosinophils and lymphocytes.

PMID- 15432050
TI  - The use of Xenopus laevis, Bufo bufo and Rana esculenta as test animals for
      gonadotrophic hormones; survey of previous investigations.

PMID- 15432051
TI  - Aqueous solutions of steroid hormones.

PMID- 15432052
TI  - The ester hydrolysis and extraction of bovine urinary steroids.

PMID- 15432053
TI  - Investigations on the chemical determination of corticoids in urine.

PMID- 15432054
TI  - Biochemical and clinical studies in rheumatoid arthritis during administration of
      adrenocorticotrophic hormone (ACTH).

PMID- 15432055
TI  - Attempts to reproduce the effects of ACTH or of compound E in rheumatoid
      arthritis by means of other hormones and steroids.

PMID- 15432056
TI  - Effect of ACTH and cortisone on rheumatic fever.

PMID- 15432057
TI  - Proliferative effect of testosterone propionate on human vaginal epithelium.

PMID- 15432058
TI  - The formation of lactic acid in the vagina of the adult rat.

PMID- 15432059
TI  - The mitogenic actions of testosterone propionate and of oestrone on the epidermis
      of the adult male mouse.

PMID- 15432060
TI  - [Personality and emotional conflicts as etiological factors in acute ulcerative
      colitis].

PMID- 15432061
TI  - [Radiology of hemorrhagic rectocolitis].

PMID- 15432062
TI  - [General conclusions of the questions of hemorrhagic rectocolitis].

PMID- 15432063
TI  - [Standardization of the treatment of peptic ulcer].

PMID- 15432064
TI  - [Diaphragmatic eventration; radio-anatomo-clinical diagnosis and treatment].

PMID- 15432065
TI  - [Benign tumors of the small intestine; surgical pathology and histopathology].

PMID- 15432066
TI  - [Synthesis of vitamin A in the liver of the dog, following portal injection of
      carotene].

PMID- 15432067
TI  - [Aureomycin therapy of epidemic hepatitis].

PMID- 15432068
TI  - [Idiopathic steatorrhoea].

PMID- 15432069
TI  - [Determination of alimentary hyperlipemia in fatty diarrhea].

PMID- 15432070
TI  - [Several cases of sprue from the authors' own experience].

PMID- 15432071
TI  - [An autopsy performed under exceptionally favorable conditions on a case of
      sprue].

PMID- 15432072
TI  - [Gastritis].

PMID- 15432073
TI  - [Moderate congenital ptosis in five generations].

PMID- 15432075
TI  - The prognosis of disease.

PMID- 15432074
TI  - Standard error and medicine.

PMID- 15432076
TI  - Venereal disease and prostitution.

PMID- 15432077
TI  - Obesity and diabetes.

PMID- 15432078
TI  - The normal size of sella turcica.

PMID- 15432079
TI  - The distribution of stature is hypernormal.

PMID- 15432080
TI  - Treatment of pernicious anemia with animal protein concentrates of bacterial
      origin.

PMID- 15432081
TI  - [Effect of repeated massive doses of nitrogen mustard (methyl-bis-beta-chlorethyl
      amine) on the blood picture and hemopoietic organs of the rabbit].

PMID- 15432082
TI  - Splenic cytopenia in childhood.

PMID- 15432083
TI  - [Clinical and hematological observations on the development of lymphatic
      follicles in the bone-marrow].

PMID- 15432084
TI  - Congenital hemolytic anemia in the Negro.

PMID- 15432085
TI  - [Modifications of erythroblasts due to the effect of nitrogen mustard].

PMID- 15432086
TI  - [Effect of desoxycorticosterone acetate on lymphatic tissue and lymphocyte count
      in peripheral blood].

PMID- 15432087
TI  - [The hematocrit and its diagnostic significance].

PMID- 15432088
TI  - [Postscarlatinal fulminant purpura with deficient V factor and excessive
      antithrombin].

PMID- 15432089
TI  - [Inner bodies and fluorescence].

PMID- 15432090
TI  - Scandinavian literature on hematology from the year 1949.

PMID- 15432091
TI  - Serum magnesium in normal men and women.

PMID- 15432092
TI  - [Alkali phosphatase in the cells of normal and pathological bone marrow and
      peripheral blood].

PMID- 15432093
TI  - [Use of ribonuclease (Brachet's test) in hematologic diagnosis].

PMID- 15432094
TI  - Bone marrow findings in a case of pernicious anemia, complicated by acute
      infection.

PMID- 15432095
TI  - [Methods of taking the leukocyte count in laboratory white rats].

PMID- 15432096
TI  - [Physiopathology of mast cells; accumulation and liberation of heparin].

PMID- 15432097
TI  - [Lymphosarcoma terminating in acute leukemia, as an illustration of elective
      metastasis].

PMID- 15432098
TI  - [Proceedings of the first Congress of the Society for the Study of Infectious and
      Parasite Diseases; ancylostomiasis].

PMID- 15432099
TI  - [Behavior of complement power in ancylostomiasis].

PMID- 15432100
TI  - [Lipasemia in ancylostomiasis].

PMID- 15432101
TI  - [Diastasemia in ancylostomiasis].

PMID- 15432102
TI  - [Steatorrhea in ancylostomiasis].

PMID- 15432103
TI  - [Duodenitis in ancylostomiasis; radiological study].

PMID- 15432104
TI  - [Distribution of ancylostomiasis in Naples].

PMID- 15432105
TI  - [Behavior of serum iron in ancylostomiasis].

PMID- 15432106
TI  - [Grave anemia of ancylostomiasis, accompanying grave hemorrhagic manifestations
      of skin and mucosa].

PMID- 15432107
TI  - [Ancylostomiasis in Padua].

PMID- 15432108
TI  - [Pancreas and tuberculosis. IV. Tubercle bacilli injected into the pancreatic
      parenchyma are eliminated naturally].

PMID- 15432109
TI  - [Amebiasis in Sardinia; observations on diagnosis in endemic zones].

PMID- 15432110
TI  - [Most recent studies on cortisone and ACTH in the treatment of rheumatic diseases
      and the use of other substances as substitutes].

PMID- 15432111
TI  - [Photodermatosis of familial character].

PMID- 15432112
TI  - Wandering pacemaker.

PMID- 15432113
TI  - [Treatment of bronchial asthma with panroentgenotherapy].

PMID- 15432114
TI  - [Calcification resulting from antero-septal cardiac infarct; differentiation from
      calcifying pericarditis by means of transverse axial stratigraphy].

PMID- 15432115
TI  - [Significance of calcareous plaques of the thoracic aorta; a case of unusual
      aortic calcification].

PMID- 15432116
TI  - [Hematuria, monosymptomatic manifestation of dicumarol intoxication].

PMID- 15432117
TI  - Tuberculosis mortality in the Philippines in 1940.

PMID- 15432118
TI  - Thyroid surgery in the Philippine General Hospital.

PMID- 15432119
TI  - Is there sodium and potassium deficiency in early childhood in the Philippines?

PMID- 15432120
TI  - Proctoscopic diagnosis of rectal schistosomiasis.

PMID- 15432121
TI  - Studies on the life cycle of the human lung fluke (Paragonimus) in the
      Philippines: a preliminary report.

PMID- 15432122
TI  - Clinical studies on malignant hepatitis.

PMID- 15432123
TI  - Neurological complications in acute infectious hepatitis.

PMID- 15432124
TI  - The prognosis of diabetes mellitus; a study of 221 patients surviving at least 15
      years.

PMID- 15432125
TI  - A study of histamine-induced gastric secretion during artificial fever.

PMID- 15432126
TI  - A study of thrombopoiesis before and after spontaneous remission in a case of
      acute idiopathic thrombopenic purpura.

PMID- 15432127
TI  - Aneurysm of pulmonary artery.

PMID- 15432128
TI  - On treatment of barbiturate poisoning.

PMID- 15432129
TI  - Cryoglobulinemia; a survey and a case report.

PMID- 15432130
TI  - Air-borne infections; modes of contagion in diphtheria.

PMID- 15432131
TI  - The so-called Cushing's Syndrome, its history, terminology and differential
      diagnosis.

PMID- 15432132
TI  - An analytical study of splenectomized cases after traumatic rupture of healthy
      spleens.

PMID- 15432133
TI  - Recurrent gastrointestinal hemorrhage in hereditary hemorrhagic telangiectasia
      (Osler).

PMID- 15432134
TI  - [Individual and general rhythm of diurnal variations in vital capacity].

PMID- 15432135
TI  - Another case of hyperglobulinemia and affection of the central nervous system.

PMID- 15432136
TI  - A follow-up examination of 138 cases of subarachnoid hemorrhage.

PMID- 15432137
TI  - The role of infection in myasthenia gravis.

PMID- 15432138
TI  - Deep reflexes in Parkinson's syndrome.

PMID- 15432139
TI  - Plicated tongue in Melkersson's syndrome and in paralysis of the facial nerve.

PMID- 15432140
TI  - Data on the pathology of disseminated sclerosis; the distribution of the
      thromboplastic and anti-coagulating substances of the central nervous system and
      the susceptibility to thrombosis of its venous capillaries.

PMID- 15432141
TI  - Data on the pathology of disseminated sclerosis; the pathology of the blood
      clotting system of disseminated sclerosis.

PMID- 15432142
TI  - [Ether-extractible bilirubin].

PMID- 15432143
TI  - Guillain-Barre's syndrome in infectious mononucleosis.

PMID- 15432144
TI  - Isolation of a virus from six cases of sarcoidosis, lymphogranulomatosis benigna
      Schaumann.

PMID- 15432145
TI  - Immunological analysis of diphtheria antigens by the gel diffusion method.

PMID- 15432146
TI  - Biochemical versus hemodynamic factors in the origin of hypertensive heart
      disease.

PMID- 15432147
TI  - Cardiovascular and renal findings in long-standing diabetes mellitus; a study of
      221 patients surviving at least 15 years.

PMID- 15432148
TI  - The role of glutamine in metabolism, with special regard to the formation of uric
      acid in gout.

PMID- 15432149
TI  - Craniopharyngiomas.

PMID- 15432150
TI  - Pyloric stenosis in sarcoidosis.

PMID- 15432151
TI  - [Protein tolerance test in diabetes].

PMID- 15432152
TI  - [Electrocardiographic diagnosis of chronic strain of the right ventricle using
      the thoracic lead].

PMID- 15432153
TI  - Health hazards in the manufacture of alkaline accumulators with special reference
      to chronic cadmium poisoning; a clinical and experimental study.

PMID- 15432154
TI  - Experimental and clinical investigations into the effect of parenterally
      administered iron.

PMID- 15432155
TI  - Some biological aspects of prognathism and occlusion of the teeth.

PMID- 15432156
TI  - Anomalies of the lateral incisor in cases of harelip and cleft palate.

PMID- 15432157
TI  - Reduction of the solubility of enamel surfaces.

PMID- 15432158
TI  - Cleft palate, an experiment.

PMID- 15432159
TI  - [Pathology of a cut flexor tendon].

PMID- 15432160
TI  - [Direct nailing of low tri-malleolar torsion fracture, with astragalotibial
      diastasis].

PMID- 15432161
TI  - [Nineteen cases of white tumor of the knee; early case-finding].

PMID- 15432162
TI  - [The Key-Charnley frame for the postoperative maintenance of resections of the
      knee].

PMID- 15432163
TI  - [Spondylolysis, fractures of the articular processes and spondylolisthesis].

PMID- 15432164
TI  - [Impressions and results of the use of penicillin and streptomycin in
      orthopedics].

PMID- 15432165
TI  - [Critical study of a personal series of surgical reductions of congenital hip
      dislocations in children].

PMID- 15432166
TI  - [Considerations of treatment of congenital dislocations of the hip].

PMID- 15432167
TI  - [Sub-cotyloidian geodes].

PMID- 15432168
TI  - [Treatment of recurrent dislocations of the shoulder].

PMID- 15432169
TI  - [Note on coxa vara in adolescents].

PMID- 15432170
TI  - [New apparatus for the reduction of a tibiofibular diastasis].

PMID- 15432171
TI  - [Sequelae of malleolar fractures due to industrial accident].

PMID- 15432172
TI  - [Treatment of the sequelae of ankle injuries].

PMID- 15432173
TI  - [Not Available].

PMID- 15432174
TI  - On serious birth injuries of the brain after normal delivery a terme.

PMID- 15432175
TI  - On universal reactions in connection with treatment of asthmatic children with
      bacterial vaccines.

PMID- 15432176
TI  - The effects of adrenocorticotrophic hormone (ACTH) in a case of juvenile
      rheumatoid arthritis.

PMID- 15432177
TI  - [Streptomycin therapy of influenzal meningitis].

PMID- 15432178
TI  - Evaluation of the effect of d-amphetamine sulfate in the treatment of obesity in
      children.

PMID- 15432179
TI  - Diplomycin treatment in a case of tuberculous meningitis.

PMID- 15432180
TI  - Hypoplasia of the mandible as a cause of respiratory difficulties in the infant.

PMID- 15432181
TI  - Acute quinidine poisoning in a 3 year old child, with special reference to the
      electrocardiographic changes.

PMID- 15432182
TI  - [Contribution to the study of the digestive pathology in the infant].

PMID- 15432183
TI  - [Contribution to the study of the digestive pathology of the infant].

PMID- 15432184
TI  - [Osteoarthritis from Salmonella suipestifer var. Kunzendorf in infants; 2 cases].

PMID- 15432185
TI  - [Biometric study of the influence of sex and age on bilirubinemia in normal
      infants].

PMID- 15432186
TI  - [Leukocyte picture in infantile tuberculosis].

PMID- 15432187
TI  - [Mechanism of the appearance of hypoprothrombinemia of p-aminosalicylic acid].

PMID- 15432188
TI  - [Serum cholinesterase in infantile tuberculosis].

PMID- 15432189
TI  - [Action of synthetic antihistamines on the blood crasis and on the temperature of
      the normal infant].

PMID- 15432190
TI  - [Nitrogen metabolism in the thymectomized rat].

PMID- 15432191
TI  - [Calcium fractions of the body fluids. I. Microdetermination].

PMID- 15432192
TI  - [Calcium fractions of the body fluids. II. Calcium picture of the serum and its
      clinical significance].

PMID- 15432193
TI  - [Active calcium of the cerebrospinal fluid in spasmophilia].

PMID- 15432194
TI  - [Iontophoresis and calcium fractions of the blood and cerebrospinal fluid].

PMID- 15432195
TI  - [Variations of active calcium after pneumoencephalography].

PMID- 15432196
TI  - [Considerations on the Ca/P ratio of the blood].

PMID- 15432197
TI  - [Reliability of a new micromethod for the determination of calcium in biological
      fluids].

PMID- 15432198
TI  - [Contribution to the problem of capacity for lactation].

PMID- 15432199
TI  - [Atypical, incomplete and infrequent intestinal invaginations in infants;
      diagnosis and treatment].

PMID- 15432200
TI  - [Antituberculosis vaccination in children (excluding the technic in the
      newborn)].

PMID- 15432201
TI  - [Efficacy of antidiphtheria vaccination].

PMID- 15432202
TI  - [Anthropology of growth; some anthropometric data for a study of the physical
      development of the Spanish child].

PMID- 15432203
TI  - [Value of Spehl's vital coefficient].

PMID- 15432204
TI  - [Serological diagnosis of kala-azar; contribution to the study of the Sanchis
      Bayarri-Marco Ahuir reaction].

PMID- 15432205
TI  - [Infantile sexuality and the Oedipus complex].

PMID- 15432206
TI  - [Cranium in infants].

PMID- 15432207
TI  - [Epidemiology and therapy of typhoid fever in children].

PMID- 15432208
TI  - [Tuberculous meningitis cured with streptomycin].

PMID- 15432209
TI  - [Acute whooping cough and streptomycin].

PMID- 15432210
TI  - [Maternal tuberculosis, dystrophy and infantile tuberculosis].

PMID- 15432211
TI  - Studies on the stimulation mechanism of gastric secretion.

PMID- 15432212
TI  - [Therapeutic criteria in progressive chronic polyarthritis; recommendations of
      the Commission for the Study of Therapeutic Criteria of the American Association
      for Rheumatic Diseases].

PMID- 15432213
TI  - [Coxarthritis].

PMID- 15432214
TI  - [The overhang sign and the screw sign in the early diagnosis of coxarthritis].

PMID- 15432215
TI  - Percutaneous angiography of the vertebral artery.

PMID- 15432216
TI  - Patent ductus arteriosus; diagnosis by introduction of catheter through ductus
      from pulmonary artery into aorta.

PMID- 15432217
TI  - [Fever in connection with brachyradium therapy of otherwise uncomplicated
      cervical carcinoma].

PMID- 15432218
TI  - New instruments for bronchography.

PMID- 15432219
TI  - Hodgkin's disease and pregnancy.

PMID- 15432220
TI  - Physical aspects of the roentgen radiation from a beryllium window tube operated
      over the range 2-50 K.V.P. for clinical purposes.

PMID- 15432222
TI  - THE exchange of diagrams and data between radiation therapy centres.

PMID- 15432221
TI  - Rolf Bull Engelstad in memoriam.

PMID- 15432224
TI  - [Treatment of intrathoracic tumors of neurogenic origin].

PMID- 15432223
TI  - [A mixture of amino acids and dextrin for treatment of severe nutritional
      disorders in infancy].

PMID- 15432225
TI  - [Treatment of polyglandular disorders, especially paradoxical obesity, with
      desoxycorticosterone acetate].

PMID- 15432226
TI  - [Plasma therapy].

PMID- 15432227
TI  - [Herpes zoster following transfusion].

PMID- 15432228
TI  - [Oral application of penicillin].

PMID- 15432229
TI  - [Degenerative disorders of the hearing with and without otosclerosis, and their
      treatment].

PMID- 15432230
TI  - [Combined conteben and PAS therapy of pulmonary tuberculosis].

PMID- 15432231
TI  - [Follow-up studies and more detailed studies of cerebrospinal fluid protein in
      poliomyelitis].

PMID- 15432232
TI  - [Animal experimentation in investigations of adhesion formation in the
      intraperitoneal cavity].

PMID- 15432233
TI  - [Revision of legislation concerning the control of venereal disease].

PMID- 15432234
TI  - [Diabetes and pregnancy].

PMID- 15432235
TI  - [Defective coagulation in pulmonary tuberculosis].

PMID- 15432236
TI  - [Qualitative hematology; allergic reactions of the blood cells].

PMID- 15432237
TI  - [B2 complex avitaminosis and deficiency disease].

PMID- 15432238
TI  - [Further instruction on the determination of calcium].

PMID- 15432239
TI  - [Polamidon addiction].

PMID- 15432240
TI  - [Polyneuritis following abuse of Hoffman's drops (spiritus aethereus)].

PMID- 15432241
TI  - [Maternal injuries in labor and means of prevention].

PMID- 15432242
TI  - [Analysis of causes of the formation of vesicovaginal fistulas in labor].

PMID- 15432243
TI  - [Intracranial birth injury of the newborn in relation to the course and conduct
      of labor].

PMID- 15432244
TI  - [Intracranial birth injuries in newborn].

PMID- 15432245
TI  - [Basic principles in the development of rational methods of labor conduction in
      Russian obstetrics].

PMID- 15432246
TI  - [Vascular and nervous component in the pathogenesis of toxicoses in the second
      half of pregnancy].

PMID- 15432247
TI  - [Plethysmographic data as indices of the state of the vascular system in toxemia
      during the second half of pregnancy].

PMID- 15432248
TI  - [Clinical significance of the study of the fragility of peripheral vessels in
      pregnancy].

PMID- 15432249
TI  - [Antitoxin function of the liver in normal and pathologic pregnancies].

PMID- 15432250
TI  - [Modifications of thrombocytopoiesis in pregnancy].

PMID- 15432251
TI  - [Rupture of the uterus in labor].

PMID- 15432252
TI  - [Pathogenesis of spontaneous rupture of the uterus in pregnancy].

PMID- 15432253
TI  - [Case of rupture of the uterus in the first period of pregnancy].

PMID- 15432254
TI  - [Rupture of the uterus in pregnancy].

PMID- 15432255
TI  - [Case of spontaneous rupture of the uterus during labor 3 months following
      injury].

PMID- 15432256
TI  - [Use of sea baths in gynecological inflammatory diseases and during
      menstruation].

PMID- 15432257
TI  - [Application of the electromagnet in gynecological practice].

PMID- 15432258
TI  - [Angiocardiopneumography; simplified technique; first results].

PMID- 15432259
TI  - [Acute coronary syndromes in the young; 7 observations].

PMID- 15432260
TI  - [Cardiovascular disorders in the antabuse-alcohol reaction].

PMID- 15432261
TI  - [Macrocytic anemias].

PMID- 15432262
TI  - [Considerations on a case of angina pectoris].

PMID- 15432263
TI  - [Protistene in the treatment of intestinal amebiasis].

PMID- 15432264
TI  - [Pulmonary staphylococcosis with anemia simulating a primary tuberculosis
      infection in an infant; dissociated action of penicillin on the pulmonary lesions
      and blood disorders].

PMID- 15432265
TI  - [Medical treatment of Banti's syndrome; three cases].

PMID- 15432266
TI  - [Hemorrhagic cyst of the thyroid].

PMID- 15432267
TI  - [Edematous syndrome during icterogenic hepatitis; diagnosis and prognosis].

PMID- 15432268
TI  - [Treatment of rheumatic heart valve disease by lanatosid C].

PMID- 15432269
TI  - [Large pulmonary tuberculosis caverns in the child].

PMID- 15432270
TI  - [Etiologic factors in rheumatic fever].

PMID- 15432271
TI  - [Meningitis due to Pfeiffer's bacillus; anatomo-clinical aspects].

PMID- 15432272
TI  - [Treatments of psychoanalytic inspiration in pediatrics].

PMID- 15432273
TI  - [Basis for treatment of congenital talipes equinovarus].

PMID- 15432274
TI  - [The seashore Aerium of Jean-Bart].

PMID- 15432275
TI  - [Case of gigantic splenomegaly in an Algerian].

PMID- 15432276
TI  - [Recent data on the treatment of whooping cough].

PMID- 15432277
TI  - [Nutritional level in Portugal; preliminary note].

PMID- 15432278
TI  - [Ganglioneuroma of the mesentery].

PMID- 15432279
TI  - [Behavior of the Takata-Ara, Hanger and Maclagan reactions in the medical and
      surgical tuberculosis].

PMID- 15432280
TI  - [Treatment of uremia].

PMID- 15432281
TI  - [Normal values of sodium and potassium in blood serum].

PMID- 15432282
TI  - On the direction and manifest size of the variations of potential in the human
      heart and on the influence of the position of the heart on the form of the
      electrocardiogram.

PMID- 15432283
TI  - What is the reason for the ventricular arrhythmia in cases of auricular
      fibrillation?

PMID- 15432284
TI  - Retrograde conduction to the auricles in paroxysmal ventricular tachycardia; a
      report of an unusual case diagnosed by the esophageal lead.

PMID- 15432285
TI  - A study of the V leads in congenital heart disease; with particular reference to
      ventricular hypertrophy and its diagnostic value.

PMID- 15432286
TI  - An electro cardiographic study of psychiatry patients before and after
      electroshock therapy.

PMID- 15432287
TI  - Multiple lead electrocardiograms in angina pectoris.

PMID- 15432288
TI  - Pulmonary stenosis with patent foramen ovale.

PMID- 15432289
TI  - Congenital aortic septal defect.

PMID- 15432290
TI  - Auricular calcification.

PMID- 15432291
TI  - Congenital mitral atresia, transposition of the great vessels, and congenital
      aortic coarctation; a case report and an interpretation of the anomaly.

PMID- 15432292
TI  - Congenital glycogenic tumor of the heart.

PMID- 15432293
TI  - Sudden death due to embolic occlusion of both coronary ostia in syphilitic
      cardiovascular disease.

PMID- 15432294
TI  - Studies of living interstitial cells and pieces of seminiferous tubles in
      autogenous grafts of testis.

PMID- 15432295
TI  - The effect of hypophysectomy on the adrenal cortex of the immature mouse.

PMID- 15432296
TI  - Cytological phenomena associated with experimental alterations of secretory
      activity in the adrenal cortex of mice.

PMID- 15432297
TI  - The growth pattern of the tibia in normal and ie rats.

PMID- 15432298
TI  - Effects of the pituitary growth hormone and thyroxin on growth and
      differentiation of the skeleton of the rat thyroidectomized at birth.

PMID- 15432299
TI  - The morphology of viral inclusions and their practical importance in the
      diagnosis of human disease.

PMID- 15432300
TI  - In vitro sensitivity of human pathogenic strains of streptococci to seven
      antibiotics.

PMID- 15432301
TI  - In vitro susceptibility of pneumococci to seven antibiotics.

PMID- 15432302
TI  - The complex mechanisms of the quick prothrombin test and the effect of dicumarol.

PMID- 15432303
TI  - New one-stage procedures for the quantitative determination of prothrombin and
      labile factor.

PMID- 15432304
TI  - Histologic changes produced by radiation in adenocarcinomas of the uterus;
      comparison with changes produced in squamous cell carcinomas of cervix.

PMID- 15432305
TI  - Plasma amino acids and ether-soluble phenols in uremia.

PMID- 15432306
TI  - Lipoma of the palm.

PMID- 15432307
TI  - Spectrochemical values for sodium, potassium, iron, magnesium and calcium in
      normal human plasma.

PMID- 15432308
TI  - Further observations on the technic of slide culture of the tubercle bacillus.

PMID- 15432309
TI  - Tests for cold hemagglutinins, "gamma globulin", and Weil-Felix reaction in
      infectious mononucleosis.

PMID- 15432310
TI  - Use of radioactive isotopes in study of fungi and bacteria.

PMID- 15432311
TI  - Isolation of the hypoagglutinable variant of Shigella alkalescens from the blood.

PMID- 15432312
TI  - A modification of the Friedman pregnancy test.

PMID- 15432313
TI  - Use of male Philippine frog, Rana vittigera, as test animal for diagnosis of
      early pregnancy.

PMID- 15432314
TI  - Further note on the method of preservation of sheep blood cells.

PMID- 15432315
TI  - Rapid photometric determination of blood glucose.

PMID- 15432316
TI  - A simple container for mailing of urine samples.

PMID- 15432317
TI  - Universal spring clips for blood counting chamber.

PMID- 15432318
TI  - Accessory pancreatic ducts of the major duodenal papilla.

PMID- 15432319
TI  - Studies on postmortem chemistry.

PMID- 15432320
TI  - In vitro susceptibility of pathogenic staphylococci to seven antibiotics.

PMID- 15432321
TI  - In vitro susceptibility of Hemophilus influenzae to seven antibiotics.

PMID- 15432322
TI  - Enzyme studies on human blood. VII. Prothrombin as determined with the isolation
      technic, in patients receiving dicumarol.

PMID- 15432323
TI  - The effect of intravenous administration of large doses of A and B substances.

PMID- 15432324
TI  - Renal tubular necrosis produced by India ink and carmine.

PMID- 15432325
TI  - The electrolytic resistance of the blood clot in thrombocytopenia.

PMID- 15432326
TI  - Cardiolipin antigens in the serodiagnosis of syphilis.

PMID- 15432327
TI  - Primary amyloidosis associated with hyperlipemia and hypercholesterolemia; report
      of case.

PMID- 15432328
TI  - Human infection with Cryptococcus glabratus; report of case involving uterus and
      fallopian tube.

PMID- 15432329
TI  - Mycotic infection of brain with arteritis and subarachnoid hemorrhage; report of
      case.

PMID- 15432330
TI  - Pulmonary emboli of cotton fibers.

PMID- 15432331
TI  - So-called "lupus erythematosus inclusion phenomenon" of bone marrow and blood.

PMID- 15432332
TI  - The air turbine hematocrit for measurement of the relative volume of packed red
      cells.

PMID- 15432333
TI  - A spectrophotometric method for quantitating hemoglobin in plasma or serum.

PMID- 15432334
TI  - Hemoglobin content of plasma of banked blood, and of serum of patients with
      transfusion reactions.

PMID- 15432335
TI  - Measurement and localization of an unknown dose of radioactive iodine in thyroid
      tissue.

PMID- 15432336
TI  - Chemical tests for malignancy.

PMID- 15432337
TI  - Oral treatment of pernicious anemia with subminimal doses of folic acid and
      vitamin B12.

PMID- 15432338
TI  - The routine use of the Perkin-Elmer flame photometer in the clinical laboratory.

PMID- 15432339
TI  - Modified dichromate method for determination of ethyl alcohol in biologic tissue.

PMID- 15432340
TI  - A new apparatus for isolation and preparation of aspirated bone marrow particles.

PMID- 15432341
TI  - Rapid microtechnics for identification of cultures III. Hydrogen sulfide
      production.

PMID- 15432342
TI  - The question of arabinosuria with a scheme for identifying reducing substances in
      urine.

PMID- 15432343
TI  - Modified silver stain of microorganisms in tissues.

PMID- 15432344
TI  - The isolation of Shigella boydii type 7 (Lavington) from a case of diarrhea.

PMID- 15432345
TI  - An anal swab method for detection of Enterobius vermicularis.

PMID- 15432346
TI  - A method for detection of arsenic in gastric contents.

PMID- 15432347
TI  - Allergic encephalitis and its possible relationship to human disease.

PMID- 15432348
TI  - Bronchogenic carcinoma: a study of 60 necropsies.

PMID- 15432349
TI  - The differential sheep cell agglutination test in arthritis.

PMID- 15432350
TI  - Correlation between electrophoretic and chemical partitions of serum proteins.

PMID- 15432351
TI  - Diagnosis of lipoid pneumonia by examination of sputum.

PMID- 15432352
TI  - Idiopathic hypoprothrombinemia; report of case.

PMID- 15432353
TI  - An improved method for removing the calvarium at autopsy.

PMID- 15432354
TI  - Clinicopathologic conference. Adenocarcinoma of the ampulla of Vater.

PMID- 15432355
TI  - THIRD, fourth and fifth reports of the committee for clarification of the
      nomenclature of cells and diseases of the blood and blood-forming organs.

PMID- 15432356
TI  - The nature of tuberculin.

PMID- 15432357
TI  - Ethyl butyrate hydrolyzing activity of human serum.

PMID- 15432358
TI  - Studies on nephrosis; quantitative changes in enzymes of the gastroduodenal
      fluids.

PMID- 15432359
TI  - Variations in the fermentative capacity of neisseriae.

PMID- 15432360
TI  - Fat embolism in trauma.

PMID- 15432361
TI  - Effect of ascorbic acid on osmotic fragility of normal erythrocytes in saline.

PMID- 15432362
TI  - Cytochemical study of glycogen in the diagnosis of cervical cancer.

PMID- 15432363
TI  - A reference bath for measuring body temperatures.

PMID- 15432364
TI  - A rapid one-step trichrome stain.

PMID- 15432365
TI  - Aldehyde-fuchsin: a new stain for elastic tissue.

PMID- 15432366
TI  - Aqueous dextrose solutions: a hazard in transfusions.

PMID- 15432367
TI  - Prophylaxis following accidental ingestion of Salmonella typhi.

PMID- 15432368
TI  - Neomycin blood levels in man.

PMID- 15432369
TI  - Detection of acid-fast bacilli; use of sodium hydroxide and trisodium phosphate
      as digestants in preparing specimens.

PMID- 15432370
TI  - An evaluation of certain culture media for tubercle bacilli.

PMID- 15432371
TI  - A new medium for bacteriologic diagnosis of tuberculosis.

PMID- 15432372
TI  - Fat, total cell and megakaryocyte content of sections of aspirated marrow of
      normal persons.

PMID- 15432373
TI  - Conversion of Arnold sterilizer.

PMID- 15432374
TI  - A selective stain for cytoplasmic hyaline bodies in Laennec's cirrhosis.

PMID- 15432375
TI  - A holding-board for small laboratory animals.

PMID- 15432376
TI  - Use of an ammeter with a spectrophotometer battery and charger.

PMID- 15432378
TI  - A permanent label for microslides.

PMID- 15432377
TI  - An inexpensive microscope lamp bulb.

PMID- 15432379
TI  - Attempts to isolate poliomyelitis virus from the paralyzed muscle of patients
      during the acute stage of the disease.

PMID- 15432380
TI  - Experimental urolithiasis: calcium oxalate stone.

PMID- 15432381
TI  - Mercury and lead storage in human tissues; with special reference to
      thrombocytopenic purpura.

PMID- 15432382
TI  - Correlation of clinical features of cirrhosis of liver with findings on biopsy.

PMID- 15432383
TI  - Artifacts in liver biopsies.

PMID- 15432384
TI  - Acute pancreatic necrosis; a clinicopathologic study.

PMID- 15432385
TI  - The effect of venous compression on certain blood factors.

PMID- 15432386
TI  - Production of a "Goldblatt kidney" by a neuroblastoma in an infant; report of
      case.

PMID- 15432387
TI  - Primary malignant melanoma of the vagina; case report with autopsy findings.

PMID- 15432388
TI  - Clinicopathologic conference.

PMID- 15432389
TI  - An accurate method for glucose determination.

PMID- 15432390
TI  - The flame photometer in determination of sodium and potassium.

PMID- 15432391
TI  - The testis, breast and prostate of men who die of cirrhosis of the liver.

PMID- 15432392
TI  - Reaction to accidentally injected rubber plugs.

PMID- 15432393
TI  - A rapid titrimetric method for determination of blood-sugar.

PMID- 15432394
TI  - The sternal route in measuring blood volume.

PMID- 15432395
TI  - The effect of a folic acid antagonist, 4-amino-pterolaspartic acid, in the
      treatment of polycythemia rubra vera.

PMID- 15432396
TI  - Persistent truncus arteriosus; a clinicopathologic study.

PMID- 15432397
TI  - The detection of the sickle cell trait; a comparison of the sealed moist
      preparation using capillary blood collected during venous stasis and the sodium
      bisulfite method.

PMID- 15432398
TI  - Comparison of tablets and solutions in measurement of bacterial sensitivities to
      antibiotics.

PMID- 15432399
TI  - Use of base in fluids for counting eosinophils; a method for staining
      eosinophils.

PMID- 15432400
TI  - Examination of cerebrospinal fluid and blood; simplified methods derived from the
      quantitative gold reaction.

PMID- 15432401
TI  - Rapid measurement of urea clearance.

PMID- 15432402
TI  - Culture of Enterobacteriaceae; I. A practical medium containing urea, tryptone,
      lactose and indicators.

PMID- 15432403
TI  - Culture of Enterobacteriaceae; II. Use of urea triple-sugar agar.

PMID- 15432404
TI  - A multiple tissue embedding apparatus.

PMID- 15432405
TI  - Use of male South American toad in pregnancy test.

PMID- 15432406
TI  - Ovarian hyperemia in the immature female hamster as a test for pregnancy.

PMID- 15432407
TI  - An inexpensive apparatus for drying biologicals from the frozen state.

PMID- 15432408
TI  - A method to minimize air bubbles and contamination of blood and agar plates.

PMID- 15432409
TI  - A note regarding the use of Wright's stain.

PMID- 15432410
TI  - Prediabetics: what becomes of them?

PMID- 15432411
TI  - The value of laminography in the difficult gallbladder problem.

PMID- 15432412
TI  - Comparison of effectiveness of various antacids on gastric acidity.

PMID- 15432413
TI  - Vitamin E therapy in amenorrhea.

PMID- 15432414
TI  - Liver function tests and heparin.

PMID- 15432415
TI  - Experimental changes in the dog's gallbladder.

PMID- 15432416
TI  - Streptococci and diplostreptococci and the respective "viruses" in the etiology
      and epidemiology of epidemic respiratory infections and infectious
      gastroenteritis.

PMID- 15432417
TI  - The relation of bile loss to water balance in the rat.

PMID- 15432418
TI  - The management of profuse bleeding from peptic ulcer.

PMID- 15432419
TI  - Chronic pancreatitis with steatorrhea following mumps with acute pancreatitis.

PMID- 15432420
TI  - The clinical diagnosis of jaundice.

PMID- 15432421
TI  - Pathogenesis of megaloblastic anemia in infancy; an interrelationship between
      pteroglutamic acid and ascorbic acid.

PMID- 15432422
TI  - Aerosol streptomycin treatment of advanced pulmonary tuberculosis in children.

PMID- 15432423
TI  - The pediatrician in the role of psychologist and educator.

PMID- 15432424
TI  - "Three day fever"; an acute febrile disease of childhood (further observations).

PMID- 15432425
TI  - Analysis of hearing loss patterns in a rural Illinois school system;
      considerations on specific frequencies.

PMID- 15432426
TI  - Unipolar electrocardiographic studies in congenital heart disease in infancy.

PMID- 15432427
TI  - Respiratory patterns and functional development of respiratory centers in
      premature infants.

PMID- 15432428
TI  - Use of a supplemented evaporated milk in the routine feeding of infants; its
      influence on blood serum vitamin C, the stools, and growth and development.

PMID- 15432429
TI  - Icterus precox.

PMID- 15432430
TI  - Salmonella typhimurium meningitis; report of 2 cases and review of the
      literature.

PMID- 15432431
TI  - Bilateral renal agenesis.

PMID- 15432432
TI  - Meningitis due to alpha hemolytic streptococcus; recovery in a newborn infant
      following chemotherapy.

PMID- 15432433
TI  - New needle for pediatric scalp vein infusions.

PMID- 15432434
TI  - Chronic diarrhea in infancy.

PMID- 15432435
TI  - Intussusception caused by invaginated Meckel's diverticulum; report of a case and
      comparison with 2 other cases demonstrating related pathologic findings.

PMID- 15432436
TI  - An unusual case of pyloric stenosis.

PMID- 15432437
TI  - Serological tests in the diagnosis and prognosis of coccidioidomycosis.

PMID- 15432438
TI  - Some abnormal host relationships of a rat nematode, Nippostrongylus muris.

PMID- 15432439
TI  - The ability of the avian malaria parasite, Plasmodium lophurae, to infect
      erythrocytes of distantly related species of animals.

PMID- 15432440
TI  - An epizootic due to pneumococcus type II in laboratory rats.

PMID- 15432441
TI  - Q fever in California. I. Observations on vaccination of human beings.

PMID- 15432442
TI  - Some epidemiological aspects of cirrhosis of the liver; a study of mortality
      statistics.

PMID- 15432443
TI  - Kinetics in the thermodestruction of cysts of Endamoeba histolytica in water.

PMID- 15432444
TI  - Isolation of a common cold virus in chick embryos and the clinical manifestations
      it produces in human volunteers.

PMID- 15432445
TI  - The use of radioactive phosphorus in studies of chick embryo infections with a
      common cold virus.

PMID- 15432446
TI  - Influence of arterial disease on the systolic blood pressure gradients of the
      extremity.

PMID- 15432447
TI  - The treatment of angina pectoris with a preparation of khellin (Ammi visnaga).

PMID- 15432448
TI  - Hypertrophy of the branches of the pulmonary artery, and its possible
      relationship with the so-called primary pulmonary arteriosclerosis in 2 infants
      with hypertrophy of the right heart.

PMID- 15432449
TI  - Acute primary pericarditis.

PMID- 15432450
TI  - The dosage-response curve for the comparison of mercurial diuretics.

PMID- 15432451
TI  - The distribution of radio-mercury of a mercurial diuretic in some of the body
      fluids of man.

PMID- 15432452
TI  - Studies on the use of aureomycin in hepatic disease. III. A note on aureomycin
      therapy in hepatic coma.

PMID- 15432453
TI  - Studies on the use of aureomycin in hepatic disease. IV. Aureomycin therapy in
      chronic liver disease; with a note on dermal sensitivity.

PMID- 15432454
TI  - Dilatation of the bile ducts and intrahepatic lesions with obstructive jaundice
      in rats fed diets deficient in vitamin A.

PMID- 15432455
TI  - Elevated titers of serum heterophil antibodies in three instances of monocytic
      leukemia.

PMID- 15432456
TI  - The effect of procaine administered intravenously on the cutaneous pain
      threshold.

PMID- 15432457
TI  - The effect of a fat-free diet in causing low serum cholesterol.

PMID- 15432458
TI  - Pituitary versus primary thyroid myxedema.

PMID- 15432460
TI  - Nystagmus: its mechanism and significance.

PMID- 15432459
TI  - Treatment of the patient with hyperthyroidism.

PMID- 15432461
TI  - A method for the evaluation of the effects of drugs on cardiac pain in patients
      with angina of effort; a study of khellin (visammin).

PMID- 15432462
TI  - Pain patterns in acute myocardial infarction.

PMID- 15432463
TI  - Congestive heart failure of renal origin; pathogenesis and treatment in 4 cases
      of carbon tetrachloride nephrosis.

PMID- 15432464
TI  - Chronic obstruction of major pulmonary arteries.

PMID- 15432465
TI  - Infections resulting from narcotic addiction; report of 102 cases.

PMID- 15432466
TI  - Carcinoma of the thyroid gland; a clinical and pathologic study.

PMID- 15432467
TI  - The present status of potassium therapy.

PMID- 15432468
TI  - Measurement of body water compartments.

PMID- 15432469
TI  - Significance of the renal juxtamedullary circulation in man.

PMID- 15432470
TI  - Renal physiology in infancy.

PMID- 15432471
TI  - CLINIC on psychosomatic problems; a child's reaction to adenoidectomy.

PMID- 15432472
TI  - CLINICO-PATHOLOGIC conference; renal insufficiency.

PMID- 15432473
TI  - Evidence against renal vascular shunts in a case of lower nephron nephron
      nephrosis.

PMID- 15432474
TI  - Para-aminobenzoic acid in the treatment of acute rheumatic fever.

PMID- 15432475
TI  - Caring for the premature baby.

PMID- 15432476
TI  - Well babies and hot weather.

PMID- 15432477
TI  - Tell your story well.

PMID- 15432478
TI  - Clinical courses for office nurses.

PMID- 15432479
TI  - Public relations begins at the bedside.

PMID- 15432480
TI  - A safety razor.

PMID- 15432481
TI  - Federal nursing assignments outside the United States.

PMID- 15432482
TI  - Exhibits for meetings.

PMID- 15432483
TI  - Footboards for children.

PMID- 15432484
TI  - An apprentice training program for public health nurses.

PMID- 15432485
TI  - Nursing care in collapse therapy.

PMID- 15432486
TI  - At the heels of a district nurse in Lapland.

PMID- 15432487
TI  - Urological conditions in women.

PMID- 15432488
TI  - Non-nurse assistants scrub for surgery.

PMID- 15432489
TI  - Accreditation in nursing education.

PMID- 15432490
TI  - Preventing nipple clogging.

PMID- 15432491
TI  - From square dance to drama.

PMID- 15432492
TI  - JUNGLE hospital.

PMID- 15432493
TI  - Criteria of success in the school of nursing.

PMID- 15432494
TI  - Rating students' achievement in clinical experience.

PMID- 15432495
TI  - The student as team leader.

PMID- 15432496
TI  - Student guide.

PMID- 15432497
TI  - Educational psychology.

PMID- 15432498
TI  - My day of community nursing.

PMID- 15432499
TI  - Advice to a little sister from an upper classman.

PMID- 15432500
TI  - The League of Red Cross Societies.

PMID- 15432501
TI  - Postvaccinal Encephalitis.

PMID- 15432503
TI  - Planning assignments for nursing teams.

PMID- 15432502
TI  - Getting nurses out to meetings.

PMID- 15432504
TI  - Bedside bookcase.

PMID- 15432505
TI  - Civil defense planning and nursing.

PMID- 15432506
TI  - The oil can's new role.

PMID- 15432507
TI  - Off-the-campus teaching.

PMID- 15432509
TI  - A visit with nurses abroad.

PMID- 15432508
TI  - Crossed eyes in children.

PMID- 15432510
TI  - The case for National Health Insurance.

PMID- 15432511
TI  - Compulsory health insurance for America? No.

PMID- 15432512
TI  - The major amputations.

PMID- 15432513
TI  - Nursing care for the amputee.

PMID- 15432514
TI  - Office nurses are teachers, too.

PMID- 15432516
TI  - Time for action.

PMID- 15432515
TI  - Feeding the child with cerebral palsy.

PMID- 15432517
TI  - Absenteeism in the hospital.

PMID- 15432518
TI  - The post-test.

PMID- 15432519
TI  - TESTS for practical nurses.

PMID- 15432520
TI  - Scholarships at Michael Reese Hospital School of Nursing.

PMID- 15432521
TI  - A hospital school of nursing looks at the future.

PMID- 15432522
TI  - Tested tricks for an active library.

PMID- 15432523
TI  - An evaluation of the newer obstetrics.

PMID- 15432524
TI  - Experimental studies on proteolytic enzymes in the endometrium of pregnancy to
      explain certain clinical phenomena in endometriosis.

PMID- 15432525
TI  - Nongonorrheal vulvovaginitis due to gram-negative intracellular diplococci.

PMID- 15432526
TI  - Solid ovarian tumors complicating pregnancy; a clinical-pathological study.

PMID- 15432527
TI  - Urological aspects of gynecology.

PMID- 15432528
TI  - Hospital control of sterilization and therapeutic abortion.

PMID- 15432529
TI  - Clinical evaluation of x-ray pelvimetry; a study of 1,000 patients in private
      practice.

PMID- 15432530
TI  - Studies related to the treatment of toxemia of pregnancy.

PMID- 15432531
TI  - Enterocele; an analysis of 52 cases.

PMID- 15432533
TI  - Premenstrual tension.

PMID- 15432532
TI  - Studies on prematurity; incidence and obstetrical consideration.

PMID- 15432534
TI  - Cervical changes in pregnancy, labor, and the puerperium.

PMID- 15432535
TI  - The urinary bladder during parturition: a consideration of its location, injury,
      and repair.

PMID- 15432536
TI  - Intracavitary radium at time of vaginal plastic operation.

PMID- 15432537
TI  - Coagulation defects associated with premature separation of the normally
      implanted placenta.

PMID- 15432538
TI  - Studies on Veratrum viride: standardization of intravenous technique and its
      clinical application in the treatment of toxemia of pregnancy.

PMID- 15432539
TI  - Effect of type of delivery on future childbearing.

PMID- 15432540
TI  - The use of ovarian transplants for hormonal replacement therapy.

PMID- 15432541
TI  - Length of the vagina following abdominal hysterectomy, total and subtotal.

PMID- 15432542
TI  - Pregnancy hemoglobin levels in the rural south; an evaluation of the use of the
      copper sulfate screening test in clinics.

PMID- 15432543
TI  - A clinical evaluation of the Falk procedure.

PMID- 15432544
TI  - The use of streptomycin during pregnancy.

PMID- 15432545
TI  - Edema fluid protein in patients with toxemia of pregnancy.

PMID- 15432546
TI  - A rapid aseptic scrub technique for nurseries of the newborn.

PMID- 15432547
TI  - Questionable necessity of the corpus luteum.

PMID- 15432548
TI  - Primary ovarian pregnancy.

PMID- 15432549
TI  - Metastatic carcinoma of the clitoris.

PMID- 15432550
TI  - Polyarteritis nodosa involving the female genital tract.

PMID- 15432551
TI  - Papilloma of the cervix, associated with pregnancy.

PMID- 15432552
TI  - Ruptured endometrioma with fatal peritonitis.

PMID- 15432553
TI  - Unsuspected tubal pregnancy with intraperitoneal hemorrhage.

PMID- 15432554
TI  - Ulcerative vaginitis in a case of acute monocytic leucemia.

PMID- 15432555
TI  - Diabetic retinopathy.

PMID- 15432556
TI  - New procedure for the treatment of adherent leukomas preceding keratoplasty.

PMID- 15432557
TI  - Epibulbar tumors.

PMID- 15432558
TI  - Ewing's tumor of the orbit; report of 2 cases.

PMID- 15432559
TI  - Streptothrix as a cause of follicular conjunctivitis and other obscure
      conjunctivitides.

PMID- 15432560
TI  - The effect of ACTH in glaucoma.

PMID- 15432561
TI  - Sutured contact lenses for contention of the graft in keratoplasty.

PMID- 15432562
TI  - Nondiabetic lipemia retinalis.

PMID- 15432563
TI  - The effects of microwave diathermy on the eye; an experimental study.

PMID- 15432564
TI  - Toxoplasmosis; diagnosis and treatment.

PMID- 15432565
TI  - Plastic socket and lid reconstruction.

PMID- 15432566
TI  - Presbyopia; comparative observations of white and Negro populations.

PMID- 15432567
TI  - Abducens paralysis in brucellosis; report of 2 cases.

PMID- 15432568
TI  - The effect of the eye patch on organisms of the conjunctival sac.

PMID- 15432569
TI  - Rapid lens changes in diabetes mellitus.

PMID- 15432570
TI  - Subretinal hemorrhage simulating sarcoma of the choroid.

PMID- 15432571
TI  - Mercurialentis.

PMID- 15432572
TI  - Conjunctival transplant for the treatment of pterygium.

PMID- 15432573
TI  - Correction necessary in Prince's rule.

PMID- 15432574
TI  - Cosmetic cure of alternating squint.

PMID- 15432575
TI  - Streptomycin treatment of conjunctival tuberculosis.

PMID- 15432576
TI  - A low-priced electromagnet.

PMID- 15432577
TI  - Harry Searls Gradle, 1883-1950.

PMID- 15432578
TI  - Harry Friedenwald, 1865-1950.

PMID- 15432580
TI  - A comparison of clinical methods of measuring accommodative convergence.

PMID- 15432579
TI  - The stigmatoscopy method of determining the binocular refractive status.

PMID- 15432581
TI  - Pre-orthoptic care of the very young squinter.

PMID- 15432582
TI  - Some preliminary observations on the Tuohy corneal lens.

PMID- 15432583
TI  - The effect of various illuminants on vision; with 4 case reports.

PMID- 15432584
TI  - Apparent accommodation in aphakia.

PMID- 15432585
TI  - Elmer E. Hotaling.

PMID- 15432586
TI  - European social orthodontics.

PMID- 15432587
TI  - The periodontal response to various tooth movements.

PMID- 15432588
TI  - Fundamental concepts in orthodontic education.

PMID- 15432589
TI  - Class I neutroclusion; report of a case.

PMID- 15432590
TI  - Dr. Edward Hartley Angle, his influence on orthodontics.

PMID- 15432591
TI  - Orthodontics as an adjunct to oral surgery.

PMID- 15432592
TI  - The milk stool, an aid to caries control.

PMID- 15432593
TI  - Social potentials in orthopsychiatry.

PMID- 15432594
TI  - Individual therapy and collective reform: a historian's view.

PMID- 15432595
TI  - Values and the psychiatrist.

PMID- 15432596
TI  - The genetics of differences in psychosomatic patterns in childhood.

PMID- 15432597
TI  - Observations on asthmatic children.

PMID- 15432598
TI  - A study of hostility in allergic children.

PMID- 15432599
TI  - Psychiatric study of children with pulmonary tuberculosis.

PMID- 15432600
TI  - School mental hygiene--a public health approach.

PMID- 15432601
TI  - Signposts for social psychiatry from the International Congress on Mental Health.

PMID- 15432602
TI  - A study of miners in relation to the accident problem: I. Psychiatric evaluation.

PMID- 15432603
TI  - The psychiatrist in caricature: an analysis of unconscious attitudes toward
      psychiatry.

PMID- 15432604
TI  - Desirable standards and criteria for accreditation of training clinics in child
      psychiatry.

PMID- 15432605
TI  - The geosign test: a semistructured drawing situation utilized as a screening test
      for adjustment.

PMID- 15432606
TI  - Genetic aspects of some Rorschach factors.

PMID- 15432607
TI  - The Mosaic Test: its applicability and validity.

PMID- 15432608
TI  - Reactions of mothers to pregnancy and adjustment of offspring in infancy.

PMID- 15432610
TI  - Eating and working.

PMID- 15432609
TI  - Psychiatric therapy in infancy.

PMID- 15432611
TI  - The psychotherapeutic impasse.

PMID- 15432612
TI  - Developmental stenosis of the aqueduct of Sylvius.

PMID- 15432613
TI  - Necrotizing pulmonary arteritis occurring with congenital heart disease
      (Eisenmenger complex); report of case with necropsy.

PMID- 15432614
TI  - Histogenesis of papillary cystadenoma lymphomatosum (Warthin's tumor) of the
      parotid salivary gland.

PMID- 15432615
TI  - Bilateral mammary arteritis; report of a case.

PMID- 15432616
TI  - A histologic study of muscles and nerves in poliomyelitis.

PMID- 15432617
TI  - Transfusional siderosis.

PMID- 15432618
TI  - Renal siderosis in hemoglobinuric nephropathy.

PMID- 15432619
TI  - Nuclear structure in mammary carcinoma.

PMID- 15432620
TI  - The effect of sodium sulfadiazine on the renal tubule (nephron) of the albino
      rat.

PMID- 15432621
TI  - Observations on the mitotic reaction induced in the livers of rats by thiourea.

PMID- 15432622
TI  - The importance of methionine and choline in the arrest of dietary cirrhosis of
      the liver in the rat.

PMID- 15432623
TI  - Modern concepts for the preparation of ointment bases.

PMID- 15432624
TI  - The spirit of integrated health sciences.

PMID- 15432625
TI  - Absorption and liberation of ephedrine from ion exchange resins.

PMID- 15432626
TI  - On the relationships of early primates.

PMID- 15432627
TI  - Man contemporaneous with the Swartkrans ape-man.

PMID- 15432628
TI  - A view of somatology and serology in Micronesia.

PMID- 15432629
TI  - Vital statistics of Ponape Island, Eastern Carolines.

PMID- 15432630
TI  - Birth order and body size. II. Neonatal and childhood materials.

PMID- 15432631
TI  - Ergographic study of hand dominance.

PMID- 15432632
TI  - WILLIAM King Gregory, fourth recipient of the Viking Fund medal and prize in
      physical anthropology.

PMID- 15432633
TI  - BORDER cave skull, Ingwavuma District, Zululand.

PMID- 15432634
TI  - PROCEEDINGS of the nineteenth annual meeting of the American Association of
      Physical Anthropologists.

PMID- 15432635
TI  - Oxygen consumptions of hypothermic rats and acclimatization to cold.

PMID- 15432636
TI  - Thirst and its inhibition in the stomach.

PMID- 15432638
TI  - Effects of low temperature on magnesium content of blood, body fluids and tissues
      of goldfish and turtle.

PMID- 15432637
TI  - Effect of magnesium on P31 and P32 partition in muscle.

PMID- 15432639
TI  - Comparative chemical studies in skeletal muscle following neurotomy and tenotomy.

PMID- 15432640
TI  - Experimental achlorhydria.

PMID- 15432641
TI  - Tensional changes of alveolar gas in reactions to rapid compression and
      decompression and question of nitrogen narcosis.

PMID- 15432642
TI  - Metrazol activation of acetylcholine-treated cerebral cortex.

PMID- 15432643
TI  - Experimental sensory-induced seizures.

PMID- 15432644
TI  - Role of the nervous system in experimental renal hypertension.

PMID- 15432645
TI  - Effects of hemorrhage and transfusion on renal circulation and sodium excretion
      in dogs.

PMID- 15432646
TI  - Chemical changes in experimental renal hypertension.

PMID- 15432647
TI  - Cardiovascular response of the dog to immersion hypothermia.

PMID- 15432648
TI  - Measurement of volume of dog's heart by x-ray: effect of hemorrhage, of
      epinephrine infusion, and of buffer nerve section.

PMID- 15432649
TI  - Combination of toluidine dye isomers with plasma albumin.

PMID- 15432650
TI  - Plasm dye concentration curves following two successive injections.

PMID- 15432651
TI  - Factors influencing measurement of contractile force of heart muscle in situ.

PMID- 15432652
TI  - Blood coagulation and hemorrhage following total body x-irradiation in the
      rabbit.

PMID- 15432653
TI  - Study of B-complex deficiency as a nonspecific stress.

PMID- 15432654
TI  - Induction of pseudopregnancy and its inhibition by various drugs.

PMID- 15432655
TI  - Pyrogen fever in rabbits: effects of adrenalectomy.

PMID- 15432656
TI  - Effects of hypophysectomy and adrenocorticotropic hormone on neuromuscular
      function and acetylcholine synthesis.

PMID- 15432657
TI  - Effect of age and diet on development of cataracts in the diabetic rat.

PMID- 15432658
TI  - Glycogen content of liver of alloxan diabetic rat.

PMID- 15432659
TI  - Adrenaline-thyroxin interaction in guinea pigs.

PMID- 15432660
TI  - Studies on parenteral infusion of corn glycogen; the carbohydrates found in blood
      and urine after intravenous, subcutaneous and intramuscular administration.

PMID- 15432661
TI  - Physiologic responses of certain animals and isolated preparations to mixtures of
      snake venom and egg yolk.

PMID- 15432662
TI  - Failure of the visual pathway during anoxia.

PMID- 15432663
TI  - Effect of stress upon glycosuria of force-fed depancreatized and of
      adrenalectomized-depancreatized rats.

PMID- 15432664
TI  - Effects of captivity on adrenal gland of wild Norway rat.

PMID- 15432665
TI  - Mechanism of muscular fatigue in adrenalectomized animals.

PMID- 15432666
TI  - Effect of thyroxine on oxygen consumption and heart rate following bile duct
      ligation and partial hepatectomy.

PMID- 15432667
TI  - Influence of environmental temperatures and thyroid status on sexual development
      in male mouse.

PMID- 15432668
TI  - Pulmonary water loss in desert rodents.

PMID- 15432669
TI  - Explosive decompression at high altitude.

PMID- 15432670
TI  - Regulation of breathing during electrically-induced muscular work in the intact
      anesthetized dog.

PMID- 15432671
TI  - Regulation of breathing during electrically-induced muscular work in anesthetized
      dogs following transection of spinal cord.

PMID- 15432672
TI  - Effect of respiration in midpontine animal of chemical inhibition of facilitatory
      system.

PMID- 15432673
TI  - Partition hypothesis for intestinal absorption of fat.

PMID- 15432674
TI  - Effect of anoxia on contractility and metabolism of intestinal smooth muscle.

PMID- 15432675
TI  - Effect of resection of antrum of stomach on gastric secretion in Pavlov pouch
      dogs.

PMID- 15432676
TI  - Effect of feeding cinchophen on secretion of juice by duodenal glands in dog.

PMID- 15432677
TI  - Histamine content of canine pancreatic juice and pancreatic tissue.

PMID- 15432678
TI  - Response of gastric mucous barrier in pouch dogs to repeated topical application
      of eugenol.

PMID- 15432679
TI  - Effect of sucrose, lactose, galactose and fructose on fecal excretion of biotin,
      riboflavin and PGA in the mature cotton rat.

PMID- 15432680
TI  - Mucoproteins of gastric juice and mucus and mechanism of their secretion.

PMID- 15432681
TI  - Use of radioactive phosphorus in studies of fetal circulation.

PMID- 15432682
TI  - Effect of hypoproteinemia produced by plasmapheresis on plasma and interstitial
      fluid volumes and renal clearances of dogs.

PMID- 15432683
TI  - Effect of low protein diet and plasmapheresis on fluid compartments and
      glomerular filtration rate in dogs.

PMID- 15432684
TI  - Phosphorylation of adenosine by kidney homogenates.

PMID- 15432685
TI  - Neurogenic control of the blood sugar elicited by induced variations in the body
      temperature of the chick.

PMID- 15432686
TI  - Effect of dietary levels of sodium and potassium on growth and on concentrations
      in blood plasma and tissues of white rat.

PMID- 15432687
TI  - Influence of dietary factors on hypertension induced by choline deficiency.

PMID- 15432688
TI  - Permeability of frog skin by means of radioactive tracers.

PMID- 15432689
TI  - Hepatorenal factors in circulatory homeostasis. XX. Antidiuretic action of
      hepatic vasodepressor, VDM (ferritin).

PMID- 15432690
TI  - Determination of excitability of mammalian heart at intervals throughout cardiac
      cycle.

PMID- 15432691
TI  - Effectiveness of single rectangular electrical pulses of known duration and
      strength in evoking auricular fibrillation.

PMID- 15432692
TI  - Measurement of increase in volume of tail of mouse following ischemia.

PMID- 15432693
TI  - Studies on physiologic effects of large doses of epinephrine.

PMID- 15432694
TI  - Influence of sodium pentobarbital upon course of events in experimental
      hemorrhagic shock.

PMID- 15432695
TI  - Pattern of contraction and relaxation in tortoise ventricle.

PMID- 15432696
TI  - Further evidence that inspiration increases right atrial inflow.

PMID- 15432697
TI  - Factors influencing changes in coronary flow following sympathetic nerve
      stimulation.

PMID- 15432698
TI  - Relation between length of diastole and stroke index in intact dog.

PMID- 15432699
TI  - Effects of adrenaline on flow in isolated perfused rabbit's ear.

PMID- 15432700
TI  - Effect of thyroidectomy on serum lipase and thrombin inactivation in rabbits.

PMID- 15432701
TI  - Qualitative differences between brain and lung thromboplastic suspensions.

PMID- 15432702
TI  - Thermal cutaneous vasomotor response in dogs.

PMID- 15432703
TI  - Mean blood pressure of cats under dial-urethane anesthesia.

PMID- 15432704
TI  - Total body water in man.

PMID- 15432705
TI  - Estimation of intracellular water in man.

PMID- 15432706
TI  - Observations on drinking induced by hypertonic solutions.

PMID- 15432707
TI  - Role of sodium and chloride in thirst.

PMID- 15432708
TI  - Renal mechanisms for excretion of potassium.

PMID- 15432709
TI  - Physiological basis for effects of low-protein diets on blood pressure of
      subtotally nephrectomized rat.

PMID- 15432710
TI  - Effect of choline deficiency on ACTH production and on hypertension of subtotally
      nephrectomized rats.

PMID- 15432711
TI  - Relationship of renin to early renal hypertension in the rabbit.

PMID- 15432712
TI  - Time of appearance and properties of antigonadotrophic and progonadotrophic
      substances of rabbit serum.

PMID- 15432713
TI  - Actomyosin formation by estrogen action.

PMID- 15432714
TI  - Factors affecting epinephrine content of adrenal glands.

PMID- 15432715
TI  - Effect of phosphate upon the utilization of glucose by the alloxan diabetic rat.

PMID- 15432716
TI  - Conversion of hexose to pentose by mammalian tissue.

PMID- 15432717
TI  - Obesity and food requirements in albino mice following administration of
      goldthioglucose.

PMID- 15432718
TI  - Physiological changes in intermediary metabolism of various species of ruminants
      incident to functional development of rumen.

PMID- 15432719
TI  - Effect of sham feeding on gastric motor activity of the dog.

PMID- 15432720
TI  - Etiology of explosive decompression injury.

PMID- 15432721
TI  - Nerve conduction without increased oxygen consumption: action of azide and
      fluoroacetate.

PMID- 15432722
TI  - Effects of anesthetics and convulsants on acetylcholine content of brain.

PMID- 15432723
TI  - Neuromuscular excitation: responses of normal and denervated mammalian muscle to
      bis-trimethylammonium decane (C10) and to alpha-tubocurarine.

PMID- 15432724
TI  - Physiological determination of the arrangement of the afferent connections to the
      middle ectosylvian auditory area in the dog.

PMID- 15432725
TI  - Further investigations on effect of anoxia on convulsions.

PMID- 15432726
TI  - Effect of normal and abnormal respiration on hemodynamics of experimental
      interatrial septal defects.

PMID- 15432727
TI  - Factors in variation and regulation of coronary blood flow in intact anesthetized
      dogs.

PMID- 15432728
TI  - Abnormal electrocardiograms of chickens produced by potassium deficiency and
      effects of certain drugs on the abnormalities.

PMID- 15432729
TI  - Spike potentials and cardiac effects of mammalian vagus nerve.

PMID- 15432730
TI  - Carotid-occlusion-pressor reflex: influence of existing mean arterial pressure,
      of anesthetics and of ganglionic- and adrenergic-blocking drugs.

PMID- 15432731
TI  - Evidence for conversion of carbon monoxide to carbon dioxide by the intact
      animal.

PMID- 15432732
TI  - Hepatic uptake and biliary excretion of bromsulphthalein in the dog.

PMID- 15432733
TI  - Observations concerning production and excretion of cholesterol in mammals. II.
      Excretion of bile in the rat.

PMID- 15432734
TI  - Secretion of radio-calcium in milk.

PMID- 15432735
TI  - Protein anabolic effect of testosterone propionate in adrenalectomized and normal
      rats.

PMID- 15432736
TI  - Effect of thiouracil on uptake of radioactive iodine by thyroid gland of summer
      frogs (Rana pipiens).

PMID- 15432737
TI  - Metabolism of ejaculated bull spermatozoa with particular reference to the
      glycolysis of maltose.

PMID- 15432738
TI  - Effect of thyroidectomy and thiouracil administration upon metabolism of pigeon
      bone marrow.

PMID- 15432739
TI  - Relaxation of pelvic ligaments in guinea-pigs by acetylcholine.

PMID- 15432740
TI  - Studies on the permeability of erythrocytes. III. The effect of physostigmine and
      acetylcholine on the permeability of dog, cat and rabbit erythrocytes to sodium
      and potassium.

PMID- 15432741
TI  - Acetylcholine estimation in body fluids by the acetone-sensitized frog rectus
      muscle test.

PMID- 15432742
TI  - Traumatic shock. XVII. Plasma fibrinogen in hemorrhagic shock in the dog.

PMID- 15432743
TI  - Blood-clotting time in rabbits and its variations determined with a simple
      capillary method.

PMID- 15432744
TI  - Renal clearance of sodium in the dog: effect of increasing sodium load on
      reabsorptive mechanism.

PMID- 15432745
TI  - Effects of sustained elevation of renal venous pressure on sodium excretion in
      unanesthetized dog.

PMID- 15432746
TI  - Renal excretion of sodium and potassium in the dog.

PMID- 15432747
TI  - Effect of water-soluble vitamins on thrombin and on enzymatic inactivation of
      thrombin.

PMID- 15432748
TI  - Ionic antagonism: effect of various anions on chloride excretion during osmotic
      diuresis in the dog.

PMID- 15432749
TI  - Effect of sustained expansion of extracellular fluid volume upon filtration rate,
      renal plasma flow and electrolyte and water excretion in the dog.

PMID- 15432750
TI  - Transcapillary exchange rate and volume of distribution of sulfate and sodium as
      indicated by S35O4 and Na24 in the rat.

PMID- 15432751
TI  - Fluid volumes and electrolyte concentrations in normal rabbits.

PMID- 15432752
TI  - Changes in blood plasma of guinea-pig during acute radiation syndrome.

PMID- 15432753
TI  - Numbers of erythrocytes, leucocytes and types of leucocytes, and content of
      hemoglobin in peripheral blood of female rabbits.

PMID- 15432754
TI  - Hematologic changes and death in vitamin B12-deficient rats.

PMID- 15432755
TI  - Diagnosis and prophylaxis in psychiatry at home and abroad.

PMID- 15432756
TI  - Old and new information about electroshock.

PMID- 15432757
TI  - Further experiences of the use of malononitrile in the treatment of mental
      illnesses.

PMID- 15432758
TI  - Psychiatry and the ancillary services.

PMID- 15432759
TI  - Verbal hallucinations as automatic speech; the reactivation of dormant speech
      habit.

PMID- 15432760
TI  - Transorbital lobotomy in institutional practice.

PMID- 15432761
TI  - The frequency of drug psychoses.

PMID- 15432762
TI  - Encephalitis as a psychiatric problem.

PMID- 15432763
TI  - The use of drugs in group therapy.

PMID- 15432764
TI  - A new method of treatment of affective psychoses and psychoses with depressive
      features.

PMID- 15432765
TI  - Some reflections on war and peace.

PMID- 15432766
TI  - Why state hospital superintendents fail.

PMID- 15432767
TI  - The clinical director looks at the hospital superintendent.

PMID- 15432768
TI  - What the nurse looks for in the administrator.

PMID- 15432769
TI  - Cerebral palsy; medical considerations and classification.

PMID- 15432770
TI  - Clinical report on the use of the dimethyl ether of d-tubocurarine iodide in
      electroshock therapy.

PMID- 15432771
TI  - An institutional program for committed sex deviants.

PMID- 15432772
TI  - Group therapy in sexual maladjustment.

PMID- 15432773
TI  - Strategic conditions in the psychotherapy of persons with schizophrenia.

PMID- 15432774
TI  - Complications of acute catatonic excitement; a report of 2 cases.

PMID- 15432775
TI  - A follow-up of motor withdrawal reaction to heat discomfort in patients before
      and after frontal lobotomy.

PMID- 15432776
TI  - Muscular tension as an index of effort: the effect of glare and other
      disturbances in visual work.

PMID- 15432777
TI  - Brand names and related social phenomena.

PMID- 15432778
TI  - The perception of visual surfaces.

PMID- 15432779
TI  - The role of visual factors in the maintenance of body-balance.

PMID- 15432780
TI  - The effect of sensation levels on intensive discrimination of noise.

PMID- 15432781
TI  - Gradients of generalized verbal responses.

PMID- 15432782
TI  - An olfactorium.

PMID- 15432783
TI  - A five-pointed starpattern for mirror-drawing.

PMID- 15432784
TI  - A ruler for scoring mirror-tracing errors.

PMID- 15432785
TI  - A collapsible mirror-tracing apparatus.

PMID- 15432786
TI  - Carl Emil Seashore: 1866-1949.

PMID- 15432787
TI  - Therapy of the weak ego.

PMID- 15432788
TI  - The medical view.

PMID- 15432789
TI  - Who shall practice psychotherapy?

PMID- 15432790
TI  - Why patients discontinue treatment in mental hygiene clinic.

PMID- 15432791
TI  - The clinical significance of the Mosaic and Rorschach methods.

PMID- 15432792
TI  - Bipolarity in diagnosis through art.

PMID- 15432793
TI  - PAUL Federn, M D.

PMID- 15432794
TI  - PERSONAL notes on Paul Federn.

PMID- 15432795
TI  - Public health administration in Latin America.

PMID- 15432796
TI  - Public health practices in Germany under U.S. occupation (1945-1949); brief
      historical review.

PMID- 15432797
TI  - Public health practices in Germany.

PMID- 15432798
TI  - Effective control of an outbreak of rabies in Memphis and Shelby County,
      Tennessee.

PMID- 15432799
TI  - Study in the reduction of absences from school of children with tinea capitis.

PMID- 15432800
TI  - School lunches: their nutritive value and relation to the health and diet of
      children.

PMID- 15432801
TI  - Nutrition and dietary habits of aging women.

PMID- 15432802
TI  - STATISTICAL answers to administrative questions in medical care.

PMID- 15432803
TI  - A positive mental health program.

PMID- 15432804
TI  - New horizons in hospital planning.

PMID- 15432805
TI  - Voluntary health insurance on the national scene; the program of the insurance
      companies.

PMID- 15432806
TI  - Appraisal of medical care programs.

PMID- 15432808
TI  - Problems of angiocardiography.

PMID- 15432807
TI  - We answer the public.

PMID- 15432809
TI  - Arteriography of the aorta and its branches by means of the polyethylene
      catheter.

PMID- 15432810
TI  - Angiocardiography; the prominent pulmonary artery segment.

PMID- 15432811
TI  - Lung cancer operability; angiocardiographic study of fifty-three consecutive
      proved cases of lung cancer.

PMID- 15432812
TI  - Cerebral arteriography.

PMID- 15432813
TI  - Angiocardiography; anatomo-roentgenological forms of the transposition of the
      transposition of the great vessels.

PMID- 15432814
TI  - The roentgenologic manifestations of acoustic neuromas.

PMID- 15432815
TI  - Charcot joints secondary to diabetes mellitus.

PMID- 15432816
TI  - The toxicity of roentgen rays to the chick embryo.

PMID- 15432817
TI  - The toxicity and pathological effects of roentgen rays in the chicken.

PMID- 15432818
TI  - Rupture of the uterus.

PMID- 15432819
TI  - Placental barrier in carbon monoxide, barbiturate and radium poisoning; some
      original observations in humans.

PMID- 15432820
TI  - Delayed suture in the management of wounds; analysis of 721 traumatic wounds
      illustrating the influence of time interval in wound repair.

PMID- 15432821
TI  - Primary carcinoma of the jejunum.

PMID- 15432822
TI  - Hyperextension injuries to the finger joints.

PMID- 15432823
TI  - Intertrochanteric fracture of the hip.

PMID- 15432824
TI  - Congenital coxa vara.

PMID- 15432825
TI  - Lymphomas of the anorectum.

PMID- 15432826
TI  - Diagnosis of cancer of the rectum by cytology.

PMID- 15432827
TI  - Carcinoma of the colon and rectum.

PMID- 15432828
TI  - Bilateral renal calculi.

PMID- 15432829
TI  - Traumatic aneurysm of the radial artery.

PMID- 15432830
TI  - Surgical treatment of varicocele.

PMID- 15432831
TI  - Sciatic scoliosis.

PMID- 15432832
TI  - Esophageal intubation for repair of pharyngo-esophageal diverticulum.

PMID- 15432833
TI  - Appendicitis in the American Negro.

PMID- 15432834
TI  - Rincon method of sterilization.

PMID- 15432835
TI  - Further observations on the clinical value of cholangiography.

PMID- 15432836
TI  - Transverse oblique muscle-splitting incision for cholecystectomy.

PMID- 15432837
TI  - Von Recklinghausen's disease of the small intestine associated with skin lesions.

PMID- 15432838
TI  - Segmental resection of the lung for aspergillosis.

PMID- 15432839
TI  - Intussusception due to inverted Meckel's diverticulum.

PMID- 15432840
TI  - Tardy ulnar palsy.

PMID- 15432841
TI  - Retroperitoneal lipomas.

PMID- 15432842
TI  - Negative pressure unit.

PMID- 15432844
TI  - An improved Mikulicz spur-crushing clamp.

PMID- 15432843
TI  - New instrument to simplify removal of water from the light carrier tube of a Buie
      proctoscope.

PMID- 15432845
TI  - New, simple combined instrument for uterotubal insufflation and endometrial
      biopsy.

PMID- 15432846
TI  - Oral and pharyngeal complications of chloramphenicol (chloromycetin) therapy.

PMID- 15432847
TI  - Nose and throat practice and viral infection of the upper respiratory tract.

PMID- 15432848
TI  - Venous pressure determinations in clinical practice: the effect of tetraethyl
      ammonium in congestive failure.

PMID- 15432850
TI  - Role of the esophagus in local and systemic disease.

PMID- 15432849
TI  - ACTH and cortisone (compound E).

PMID- 15432851
TI  - Cancer diagnosis in a small community hospital; aspiration biopsy.

PMID- 15432852
TI  - The clinical significance of chronic gastritis.

PMID- 15432853
TI  - The treatment of various infections with single doses of 300,000 units of
      procaine penicillin in oil plus aluminum monostearate.

PMID- 15432854
TI  - Psychotherapy in general practice; acute anxiety states and their treatment.

PMID- 15432855
TI  - A psychobiologic approach to the problem of obesity.

PMID- 15432856
TI  - Psychotherapy in psychosomatic medicine.

PMID- 15432857
TI  - Chronic primary Friedlander pneumonia: report of a case with prompt clinical and
      roentgen cure following streptomycin therapy.

PMID- 15432858
TI  - Mucoserous dyssecretosis (Sjogren's syndrome); non-ocular features.

PMID- 15432859
TI  - Review of the headache problem.

PMID- 15432860
TI  - Renal complications of cardiac disease: three case histories.

PMID- 15432861
TI  - The inverted T wave in precordial leads.

PMID- 15432862
TI  - Combined anti-amebic and antibacterial treatment of intestinal amebiasis.

PMID- 15432863
TI  - Two new drugs in the treatment of amebiasis.

PMID- 15432864
TI  - Salmonellosis; a case of human gastro-enteritis attributed to Salmonella
      pullorum.

PMID- 15432865
TI  - COR pulmonale with polycythemia.

PMID- 15432866
TI  - STEIN-Leventhal syndrome.

PMID- 15432867
TI  - The prediction of success in the VA training program in clinical psychology.

PMID- 15432868
TI  - AMERICAN Board of Examiners in Professional Psychology policies and procedures.

PMID- 15432869
TI  - The psychologist as speaker.

PMID- 15432870
TI  - Survey of psychological service centers.

PMID- 15432871
TI  - A survey of psychologists in four midwestern states.

PMID- 15432872
TI  - A survey of psychologists in Illinois.

PMID- 15432873
TI  - Clinical interpretation of the Middlebrook-Dubos hemagglutination test.

PMID- 15432874
TI  - Human pharmacology of p-formylacetanilide thiosemicarbazone (myvizone).

PMID- 15432875
TI  - The effect of 4-acetylaminobenzal thiosemicarbazone (tibione) on experimental
      tuberculosis in guinea pigs.

PMID- 15432876
TI  - The effect of dihydrostreptomycin para-aminosalicylate on experimental
      tuberculosis in guinea pigs.

PMID- 15432877
TI  - The inability of p-aminosalicylic acid to delay the emergence of streptomycin
      resistant tubercle bacilli in mice.

PMID- 15432878
TI  - The clinical toxicity of sulphetrone.

PMID- 15432880
TI  - Experiences with surgical reconstruction of the trachea.

PMID- 15432879
TI  - Vertical tomography of the thorax.

PMID- 15432881
TI  - Rehabilitation of the tuberculous in Philadelphia; a study of the effectiveness
      of the program of rehabilitation in Philadelphia for a ten-year period, July 1,
      1949.

PMID- 15432882
TI  - Miliary tuberculosis and pregnancy.

PMID- 15432883
TI  - Eroding calcified mediastinal lymph nodes.

PMID- 15432884
TI  - Artificial pneumoperitoneum complicated by pregnancy.

PMID- 15432885
TI  - The hemagglutination test in tuberculosis.

PMID- 15432886
TI  - Transmission of streptomycin-resistant tubercle bacilli.

PMID- 15432887
TI  - Boeck's sarcoid; a review based upon a clinical study of fifty-two cases.

PMID- 15432888
TI  - Genetic studies on the development of resistance to neomycin and
      dihydrostreptomycin in Myobacterium ranae.

PMID- 15432889
TI  - Effect of neomycin on the tubercle bacillus and in experimental tuberculosis of
      guinea pigs.

PMID- 15432890
TI  - Electrocardiograms with prominent S waves in all standard limb leads; associated
      patterns in multiple precordial leads.

PMID- 15432891
TI  - A study of 200 cases of tuberculous pleurisy with effusion.

PMID- 15432892
TI  - Massive pulmonary hemorrhage in tuberculosis; a report of two unusual cases.

PMID- 15432893
TI  - Gastric dilatation following left phrenic interruption treated with urethane of
      beta-methylcholine (urecholine).

PMID- 15432894
TI  - Differential response to metabolites of M. tuberculosis H37Rv and H37Ra.

PMID- 15432895
TI  - [Immediate care of the newborn with our table].

PMID- 15432896
TI  - [Perinatal mortality; standardization of maternity and private hospitals; prize
      for the best functional activity].

PMID- 15432897
TI  - [Fetal distress; physicochemical bases of treatment; oxygen therapy during
      labor].

PMID- 15432898
TI  - [Treatment of old dislocations of the shoulder].

PMID- 15432899
TI  - [Rectal blastomycosis].

PMID- 15432900
TI  - [Treatment of pemphigus foliaceus, pemphigus vegetans and severe pemphigus
      vulgaris with aureomycin].

PMID- 15432901
TI  - [Semeiology and pathology of the spleen; classification of diseases of the
      spleen; concept of hypersplenism].

PMID- 15432902
TI  - [Clinical aspects and treatment of osteoarticular tuberculosis].

PMID- 15432903
TI  - [Galli-Mainini test].

PMID- 15432904
TI  - [Hypernephroid tumor of the ovary].

PMID- 15432906
TI  - [Concept, diagnosis and treatment of thrombosis and thrombophlebitis].

PMID- 15432905
TI  - [Two recent tests for the biological diagnosis of pregnancy].

PMID- 15432907
TI  - [Spondylolisthesis].

PMID- 15432908
TI  - [Ventriculocisternostomy: the Torkildsen operation].

PMID- 15432909
TI  - [Parietotemporal ventriculoarachnoidostomy with tube, in the treatment of blocked
      hydrocephalus].

PMID- 15432910
TI  - [DDT-resistant flies].

PMID- 15432911
TI  - [Case of early syphilis resistant to treatment].

PMID- 15432912
TI  - [Dermatosis papulosa nigra (Castellani)].

PMID- 15432913
TI  - [Experimental Brazilian blastomycosis; evolution in the guinea pig].

PMID- 15432914
TI  - [Probable virus urethritis treated with aureomycin].

PMID- 15432915
TI  - [Technical considerations on surgery of renal tumors].

PMID- 15432916
TI  - [Psychoanalytic approach to essential hypertension].

PMID- 15432917
TI  - [Ureteroenterostomy: its importance in gynecology].

PMID- 15432918
TI  - [Acute hepatitis].

PMID- 15432919
TI  - [Painful trigeminal syndrome, paroxysmal form].

PMID- 15432920
TI  - [Introduction to dental physiology and therapy].

PMID- 15432921
TI  - [French dental institutions; impressions of a study trip to Paris].

PMID- 15432922
TI  - [Etiopathology and treatment of noma].

PMID- 15432923
TI  - [Congenital cysts of the jaws].

PMID- 15432924
TI  - [Tissular reactions to various medications used in odontology].

PMID- 15432925
TI  - [Dental caries and treatment].

PMID- 15432926
TI  - [General pathology of infection].

PMID- 15432927
TI  - [Psychosurgery].

PMID- 15432928
TI  - [Histological study of hemorrhages in the nerve tissue. I. Observations in man].

PMID- 15432929
TI  - [Hemianopsia].

PMID- 15432930
TI  - [Investigations on the endemia of coccidioidomycosis in the central zone of the
      Paraguayan Chaco].

PMID- 15432931
TI  - [Nature or significance of the "steering wheel" form of Paracoccidioides
      brasiliensis].

PMID- 15432932
TI  - [Mathematical study of the contractility of the human uterus].

PMID- 15432933
TI  - [Defensive proteinase and diagnosis].

PMID- 15432934
TI  - [French pharmacists who formed part of Napoleon's army during the invasion of
      Spain].

PMID- 15432935
TI  - [Considerations on the existence of the atomic bomb and means of defense against
      its radioactive action].

PMID- 15432936
TI  - [Studies in the Archivo General de Indias of Seville; the botanical expedition to
      the new kingdom of Granada or Santa Fe].

PMID- 15432937
TI  - [Lateral movement of the knee joint].

PMID- 15432938
TI  - [History of esophagoplasty; description of the first prethoracic esophagoplasty,
      performed in 1906 by Cesar Roux].

PMID- 15432939
TI  - [Studies in comparative anatomy; aorta of the gorilla].

PMID- 15432940
TI  - [The anatomy of the anthropoid larynx].

PMID- 15432941
TI  - [Comparative anatomy of the spleen, liver, intestinal tract, and kidneys of the
      gorilla].

PMID- 15432942
TI  - [On the differentiation of the genera Bison and Bos by means of the astragalus].

PMID- 15432943
TI  - [Honorary members of the Anatomical Society].

PMID- 15432945
TI  - Some psychosomatic aspects of general anesthesia.

PMID- 15432944
TI  - [International bibliography of human and vertebrate anatomy for the years 1948-49
      with addenda for the years 1945-47].

PMID- 15432946
TI  - Curare in the management of autonomic reflexes.

PMID- 15432947
TI  - A combined keysort anesthesia and recovery room record.

PMID- 15432948
TI  - The control of respiration in anesthesia.

PMID- 15432949
TI  - The effects of aliphatic sympathomimetic amines on cardiac automatic tissue in
      dogs under cyclopropane.

PMID- 15432950
TI  - A comparative study of rectal pentothal and morphine for basal anesthesia upon
      children for tonsillectomy.

PMID- 15432951
TI  - The comparative anesthetic activity of the aliphatic ethers.

PMID- 15432952
TI  - A 26 gauge lumbar puncture needle: its value in the prophylaxis of headache
      following spinal analgesia for vaginal delivery.

PMID- 15432953
TI  - An evaluation of hyaluronidase in local and nerve block analgesia: a review of
      519 cases.

PMID- 15432954
TI  - The administration of nitrous oxide and oxygen.

PMID- 15432955
TI  - The use of pentothal sodium-pentobarbital sodium combination in prolonged
      surgical procedures.

PMID- 15432956
TI  - Preoperative preparation and choice of anesthetic agents.

PMID- 15432957
TI  - A proposed new device for the administration of oxygen.

PMID- 15432958
TI  - The "operiscope" as an aid during anesthesia.

PMID- 15432959
TI  - Thromboembolic disease; a discussion of the problem in surgical patients with
      particular reference to the fatal embolus.

PMID- 15432960
TI  - A new approach to the sclerotherapy of varicose veins.

PMID- 15432961
TI  - Effect of aureomycin on the clotting time of the blood.

PMID- 15432962
TI  - The use of vasodilator drugs in chronic trench foot.

PMID- 15432963
TI  - A sensitized clotting time.

PMID- 15432964
TI  - A cardioscope.

PMID- 15432965
TI  - Vitamin E in treatment of leg ulcers.

PMID- 15432966
TI  - The history of a group of American leg amputees before 1900; some of them
      forgotten, some of them celebrated.

PMID- 15432967
TI  - The impact of cephalometry orthodontic concepts.

PMID- 15432968
TI  - Treatment of malocclusion in the mixed dentition: a panel discussion.

PMID- 15432969
TI  - Treatment of Class II, Division 1 (Angle). III. Variation and the "individuality
      hypothesis".

PMID- 15432970
TI  - [First description of chronic familial hereditary benign pemphigus].

PMID- 15432971
TI  - [Several cases of Riehl's melanosis; clinical and histological study].

PMID- 15432972
TI  - [Results of treatment of eczema by podophyllin].

PMID- 15432973
TI  - [Not Available].

PMID- 15432974
TI  - [Syringocystadenoma of the neck].

PMID- 15432975
TI  - [Epidermodysplasia verruciformis].

PMID- 15432976
TI  - [Profuse molluscum contagiosum].

PMID- 15432977
TI  - [Systematized verrucous nevi].

PMID- 15432978
TI  - [Multiple tuberous xanthomas].

PMID- 15432979
TI  - [Skin manifestations of accidental alimentary arsenic poisoning; ingestion of
      wine containing arsenic].

PMID- 15432980
TI  - [Not Available].

PMID- 15432981
TI  - [The cells of acute lupus erythematosus].

PMID- 15432982
TI  - [Perineal skin ulceration of amebic origin in the absence of any concomitant
      dysenteric syndrome].

PMID- 15432983
TI  - [Pityriasis versicolo localized exclusively on the face].

PMID- 15432984
TI  - [Cybernetics, or the art of mechanical demonstration].

PMID- 15432985
TI  - [Study on the states of nostalgia].

PMID- 15432986
TI  - [Intelligence level of deaf-mutes in relation to its etiology particularly in the
      presumably hereditary forms].

PMID- 15432987
TI  - [Streptomycin and mental disorders].

PMID- 15432989
TI  - [Indications for shock methods].

PMID- 15432988
TI  - [Applications of mental test methods to clinical psychiatry].

PMID- 15432990
TI  - [Treatment of edematous exophthalmia without hyperthyroidism].

PMID- 15432991
TI  - [Ultrastructure of the cornea and crystalline lens studied with the electron
      microscope].

PMID- 15432992
TI  - [Hutchinson's keratitis and keratoplasty: perforating grafts or lamellar grafts].

PMID- 15432993
TI  - [Some problems concerning dry keratoconjunctivitis and the syndrome of
      keratoconjunctivitis sicca].

PMID- 15432994
TI  - [Color vision tests].

PMID- 15432995
TI  - [Color vision and recent works on color vision tests].

PMID- 15432996
TI  - [Loss of vitreous during intra-capsular extraction of cataract].

PMID- 15432997
TI  - [Preservation of cadaveric cornea by immersion of the eye in paraffin oil
      maintained at 4 or 6 degrees C].

PMID- 15432998
TI  - [Inversion of the pupillary reaction to adrenalin].

PMID- 15432999
TI  - [Reflex anisocoria; clinical and experimental study].

PMID- 15433000
TI  - [Surgery and surgery combined with radiotherapy in the treatment of epitheliomas
      of the larynx and hypopharynx].

PMID- 15433001
TI  - [Physiological data in nasal respiration disorders].

PMID- 15433002
TI  - [Surgical treatment of post-otitic pain].

PMID- 15433003
TI  - [Research on the auditive function characteristic of the acoustic receptor
      systems].

PMID- 15433004
TI  - [Direct determination of deafness in relation to the spoken language].

PMID- 15433005
TI  - [A new technic of tracheostomy. A procedure of R. H. Bisi].

PMID- 15433006
TI  - [Frontal mucocele].

PMID- 15433007
TI  - [Two cases of malign tumors in children].

PMID- 15433008
TI  - [Paralysis of the dilators in a child 2 1/2 years old].

PMID- 15433009
TI  - [Radical cure of snoring by endo-nasal intervention followed by mouth appliance].

PMID- 15433010
TI  - [Streptomycin in the cervical abscess].

PMID- 15433011
TI  - [Coexistence of a benign cholesteatoma of the ear and a primary cholesteatoma].

PMID- 15433012
TI  - [Slight meningeal reactions, or the initial stages of tuberculous meningitis].

PMID- 15433013
TI  - The effect of caronamide upon the penicillin-concentration of the blood.

PMID- 15433014
TI  - [Rapid gravimetric method of hemoglobin determination].

PMID- 15433015
TI  - Congenital anomalies as factors in disorders of the pyloric passage.

PMID- 15433016
TI  - Appearance of hypertrichosis during streptomycin treatment.

PMID- 15433017
TI  - [Clinical study of a case of bilateral congenital anophthalmia with megacephalus
      and marked mental retardation].

PMID- 15433018
TI  - [Essential lymphocytophthisis; new clinical aspect of infant pathology].

PMID- 15433019
TI  - [Meconium ileus; clinical and anatomopathologic observations, and chemical
      analysis of the intestinal content in a case of fatal meconium ileus in a six-day
      old child].

PMID- 15433020
TI  - [Evaluation of serum indican and xanthoprotein in children; results of a survey
      of 37 clinical patients].

PMID- 15433021
TI  - [Case of congenital heart block with fetal parietal endocarditis].

PMID- 15433022
TI  - [Blood catalase in poliomyelitis].

PMID- 15433023
TI  - [Splenopathic panhemocytopenia, splenic inhibition of the bone marrow].

PMID- 15433024
TI  - [Clinical aspect of stenosis of the aortic isthmus during the first months of
      life].

PMID- 15433025
TI  - [Chloromycetin therapy of typhoid and paratyphoid in children].

PMID- 15433026
TI  - [Pyroracemic acid content of the blood of children in normal and pathologic
      states].

PMID- 15433027
TI  - [Alkaptonuria].

PMID- 15433028
TI  - [Behavior of pancreatic enzymes in premature infants].

PMID- 15433029
TI  - [Interstitial pneumonia in premature infants].

PMID- 15433030
TI  - [Mechanism and limitations of carob flour in the treatment of infantile diarrhea;
      clinical and experimental data].

PMID- 15433031
TI  - [Conditional sales of pharmacies].

PMID- 15433032
TI  - [Not Available].

PMID- 15433033
TI  - [Not Available].

PMID- 15433034
TI  - [Regulation of trade and use of soluble mineral arsenic compounds for the
      destruction of insects and harmful animals in agriculture].

PMID- 15433035
TI  - [Decree of May 18th 1950 concerning frauds and falsifications of tea].

PMID- 15433036
TI  - [Research in pyrogenic substances in injectable solutes; tests based on
      leukocytosis of the rabbit].

PMID- 15433037
TI  - [Research on pyrogenic substances in injectable solutes. Commentary on and
      application of the bio-assay according to the French Pharmacopoeia].

PMID- 15433038
TI  - [Research on pyrogenic substances in injectable solutes. Reduction of pyrogenic
      properties during the conservation of the solutes].

PMID- 15433039
TI  - [Adsorption of some metallic ions in very diluted solutions; coefficient of
      adsorption; number of active centers].

PMID- 15433040
TI  - [Adsorption of some metallic ions in very diluted solutions; influence of
      temperature].

PMID- 15433041
TI  - [Does the percentage of manganese in the leaves of purple Digitalis depend on the
      soil?].

PMID- 15433042
TI  - [Myrsinacae vermifuges of Madagascar].

PMID- 15433043
TI  - [Retarded action of polyvinylpyrrolidone (P.V.P.) on some plant organs].

PMID- 15433044
TI  - [Contribution to the study of the distribution of fluorine in the plant kingdom;
      tea leaves].

PMID- 15433045
TI  - [Determination of morphine in opium and preparations].

PMID- 15433046
TI  - [Experimental studies of conessine. Comparative study of the culture medium of
      dysenteric amoeba after addition of chlorhydrates of conessine or emetine].

PMID- 15433047
TI  - [Experimental studies of conessine. Cultures of dysenteric amoeba in mediums to
      which chlorhydrates of conessine or emetine were previously added].

PMID- 15433048
TI  - [Semi-industrial fabrication of a fluid extract of kola].

PMID- 15433049
TI  - [Spectrographic determination of carbon monoxide in blood].

PMID- 15433050
TI  - [Can chronic alcoholism be cured?].

PMID- 15433051
TI  - [Tests for the destruction of the tsetse fly by means of D.D.T. fumigating
      bombs].

PMID- 15433052
TI  - [A new Shigella paradysenteriae serotype: the 112 type of Cox and Wallace].

PMID- 15433053
TI  - [Pentamidine treatment of bovine trypanosomiasis due to T. congolense, T. vivax
      and T. theileri].

PMID- 15433054
TI  - [Physiology and functional pathology of the menstrual cycle of the Congo women].

PMID- 15433055
TI  - [Intestinal invagination in the Ruanda-Urundi Negroes].

PMID- 15433056
TI  - An unusual organism isolated from an outbreak of chronic intermittent fever in
      the Belgian Congo.

PMID- 15433057
TI  - [Contribution to the study of urinary bilharziosis in the Belgian Congo].

PMID- 15433058
TI  - [Distribution of the endemic goiter in the Foreami region of Popokabaka].

PMID- 15433059
TI  - [Aralen and paludrine antimalarial prophylaxis in the rural regions].

PMID- 15433060
TI  - [Rapid methods of blood staining and their use in tropical practice].

PMID- 15433061
TI  - [Antimalarial collective chemoprophylaxis in the children of the Kilo mine
      workers].

PMID- 15433062
TI  - [Depigmentationedema syndrome (kwashiorkor) in Kasai; therapeutics].

PMID- 15433063
TI  - [Study of the serum proteins in the natives of Leopoldville].

PMID- 15433064
TI  - [Xenopus test in pregnancy diagnosis at the Costermansville laboratories].

PMID- 15433065
TI  - [Diagnosis of brucellosis; relation to a case of Bang's fever].

PMID- 15433066
TI  - [Intestinal bilharziosis].

PMID- 15433067
TI  - [Experimental research on the importance of tobacco and on the significance of
      hyperhistaminemia in endarteritis obliterans].

PMID- 15433068
TI  - [Ectopia of the thyroid in the thyroid region].

PMID- 15433069
TI  - [Papilliferous cystocarcinoma in an aberrant thyroid node].

PMID- 15433070
TI  - [Calculosis of the bile duct following cholecystectomy].

PMID- 15433071
TI  - [Synthetic antihistamines and the Ito-Reenstierna reaction].

PMID- 15433072
TI  - [Indican and dermatoses; determination of indican in the blood and urine in
      subjects with skin diseases].

PMID- 15433073
TI  - [Clinico-experimental findings on the action of streptomycin in syphilis;
      indication of streptomycin in gonorrhea].

PMID- 15433074
TI  - [Case of malignant granuloma with peculiar skin manifestations].

PMID- 15433075
TI  - [Present day therapy of actinomycosis].

PMID- 15433076
TI  - [Accidental vaccinosis and Kaposi's acute varioliform pustulosis; casuistic
      contribution].

PMID- 15433077
TI  - [Anaphylactic shock and penicillin in small doses by intradermal route].

PMID- 15433078
TI  - [Rare cases of cutaneous leishmaniasis of the scalp].

PMID- 15433079
TI  - [Do blood proteins display a vehicle function for penicillin?].

PMID- 15433080
TI  - [Latest observations on the treatment of cutaneous leishmaniasis with glucantim].

PMID- 15433081
TI  - [Prof. Francesco Lisi].

PMID- 15433082
TI  - [Conjugal sterility; causes of conjugal sterility; review].

PMID- 15433083
TI  - [Conjugal sterility; diagnostic procedure in examination of a couple presumed
      sterile].

PMID- 15433084
TI  - [Spermatic mesomucinase; general considerations].

PMID- 15433085
TI  - [Spermatic mesomucinase; mucinolytic action of seminal fluid of individuals
      considered generically sterile].

PMID- 15433086
TI  - [Morphology of the human nemasperm; human nemasperm and their morphological
      modifications].

PMID- 15433087
TI  - [Morphology of the human nemasperm; chromatic variations of human nemasperm
      preserved under various surrounding conditions].

PMID- 15433088
TI  - [Dynamics of the human nemasperm; determination of the nemaspermatic velocity and
      physical expression of survival].

PMID- 15433089
TI  - [Dynamics of the human nemasperm; action of vitamins in vitro].

PMID- 15433091
TI  - [A chemico-biological control of seminal fluid: nemaspermic vitality].

PMID- 15433090
TI  - [Dehydrogenation power as an index of anaerobic metabolism of the human
      nemasperm].

PMID- 15433092
TI  - [A spermatic fertility index].

PMID- 15433093
TI  - [Observations on a case of xerophthalmic syndrome].

PMID- 15433094
TI  - [Direct oxidation of glucose by the retina].

PMID- 15433095
TI  - [Experience with an ophthalmic ointment, irgafen].

PMID- 15433096
TI  - [A case of bilateral coloboma of the mascular region associated with abducens
      paralysis].

PMID- 15433098
TI  - [Occular tension in detachment of the retina].

PMID- 15433097
TI  - [Clinical observations on retinal circulation following ligation or resection of
      the jugular vein].

PMID- 15433099
TI  - [Alterations of the iridocorneal angle in uveitis; gonioscopic observations].

PMID- 15433100
TI  - [Persistent pupillary membrane].

PMID- 15433101
TI  - [A new apparatus for biomicroscopic examination of the iridocorneal angle, of the
      retina and of the vitreous].

PMID- 15433102
TI  - [Action of the corticotropic hormone in ophthalmology].

PMID- 15433103
TI  - [Histologic contribution to the pathogenetic interpretation of keratitis
      bandelette in relation to degeneration of the lamina vitrea of the eye].

PMID- 15433104
TI  - [Research on glycolysis of the crystalline lens].

PMID- 15433105
TI  - [Transitory amaurosis from puncture of the pleural cavity].

PMID- 15433106
TI  - [Epithelial tumor of the lacrimal gland; deviating epithelioma].

PMID- 15433107
TI  - [Indications of 1930 stratigraphy compared to those of 1947 stratigraphy].

PMID- 15433108
TI  - [Tomography in osteomyelitis].

PMID- 15433109
TI  - [A seriograph for angiocardiography].

PMID- 15433110
TI  - [Experimental cardioangiography by direct puncture of the heart].

PMID- 15433111
TI  - [Segmental duodenal hypotonia].

PMID- 15433112
TI  - [Amebic granuloma of the cecum].

PMID- 15433113
TI  - [Air-borne infections and disinfection of the air].

PMID- 15433114
TI  - [Treatment of brucellosis with streptomycin and sulfadiazine].

PMID- 15433115
TI  - [Intestinal parasites with particular reference to ancylostomiasis in the Cremona
      region].

PMID- 15433116
TI  - [Presence of ancylostomiasis in the province of Parma].

PMID- 15433117
TI  - [General concepts of soil hygiene].

PMID- 15433118
TI  - [Teaching program in medicine].

PMID- 15433119
TI  - Global strategy in preventive medicine.

PMID- 15433120
TI  - The evolution and treatment of late disease of the liver.

PMID- 15433121
TI  - The familial occurrence of multiple sclerosis and its implications.

PMID- 15433122
TI  - Problems presented by pulmonary tuberculosis in patients over fifty.

PMID- 15433123
TI  - The common cold and its implications.

PMID- 15433124
TI  - Incidence of hypertension in Puerto Rico.

PMID- 15433125
TI  - The effect of dicumorol on the erythrocyte sedimentation rate.

PMID- 15433126
TI  - The chronic typhoid carrier. III. Therapy with antagonistic bacillus, antibiotics
      and sulfonamides.

PMID- 15433127
TI  - Influenza A prime: a clinical study of an epidemic caused by a new strain of
      virus.

PMID- 15433128
TI  - An outbreak of syringe transmitted hepatitis with jaundice in hospitalized
      diabetic patients.

PMID- 15433129
TI  - The effect of streptomycin on tuberculous meningitis.

PMID- 15433130
TI  - Hemolytic crisis in hereditary spherocytosis: study of a family of five with
      concurrent crises.

PMID- 15433131
TI  - Hypersensitivity to pathogenic and nonpathogenic fungi.

PMID- 15433132
TI  - Observations from forty years of medical teaching.

PMID- 15433134
TI  - Mucormycosis of the lung.

PMID- 15433133
TI  - Myelokentric acid in the treatment of acute lymphoblastic leukemia.

PMID- 15433135
TI  - Hemochromatosis: report of a case in a Negro; discussion of iron metabolism.

PMID- 15433136
TI  - B. coli septicemia in Laennec's cirrhosis of the liver.

PMID- 15433137
TI  - Idiopathic hypoprothrombinemia.

PMID- 15433138
TI  - Idiopathic hyperlipemia.

PMID- 15433139
TI  - Dr. Allen Arthur Jones.

PMID- 15433140
TI  - Dr. Hugh Leslie Moore.

PMID- 15433141
TI  - Dr. George Richards Minot.

PMID- 15433142
TI  - Biochemical significance of the competition between p-aminobenzoic acid and the
      sulphonamides.

PMID- 15433143
TI  - The utilization of antimetabolites in the study of biochemical processes in
      living organisms.

PMID- 15433144
TI  - Studies on the basis of selectivity of action of antimetabolites.

PMID- 15433145
TI  - Ion antagonism in bacteria as related to antimetabolites.

PMID- 15433146
TI  - Interference with hormonal effects by antivitamins and competition between
      structurally similar steroid hormones.

PMID- 15433147
TI  - The structural bases of some amino acid antagonists and their microbiological
      properties.

PMID- 15433148
TI  - Desoxypyridoxine observations in "acute pyridoxine deficiency".

PMID- 15433149
TI  - Studies on analogs of purines and pyrimidines.

PMID- 15433150
TI  - Pteroylglutamic acid antagonists.

PMID- 15433151
TI  - Folic acid analogs in lower animals; the Insecta: Drosophila melanogaster.

PMID- 15433152
TI  - Folic acid analogs in lower animals. The Amphibia: Rana clamitans.

PMID- 15433153
TI  - Studies of the action of 4-aminopteroylglutamic acid and its congeners in
      mammals.

PMID- 15433154
TI  - Folic acid analogs and experimental tumors.

PMID- 15433155
TI  - Mechanism and evaluation of antiseptics; introduction.

PMID- 15433156
TI  - The metabolic action of streptomycin.

PMID- 15433157
TI  - The effect of penicillin upon protein synthesis by bacteria.

PMID- 15433158
TI  - The colloidal nature of antibiotics.

PMID- 15433159
TI  - Newer antibiotics: factors influencing their antimicrobial activity.

PMID- 15433160
TI  - The effect of surface-active agents on antibiotics: an informal report.

PMID- 15433161
TI  - Studies on the synergism between bacitracin and penicillin: correlation of in
      vivo with in vitro-results.

PMID- 15433162
TI  - An approach to a correlation between in vivo and in vitro activities of
      antitubercular compounds.

PMID- 15433163
TI  - Evaluation of the paper disc assay procedure and its correlation with phenol
      coefficients.

PMID- 15433164
TI  - Mechanism of action and neutralizing agents for surface-active materials upon
      microorganisms.

PMID- 15433165
TI  - The meaning of bacteriostasis, bactericidal effect, and rate of disinfection.

PMID- 15433166
TI  - The interaction of surface active agents and proteins.

PMID- 15433167
TI  - Conductometric studies of bactericidal mechanisms.

PMID- 15433168
TI  - A new and direct approach to the evaluation of the germicidal efficiency of
      semisolid pharmaceuticals.

PMID- 15433169
TI  - The role of antagonisms in the evaluation of antiseptics.

PMID- 15433170
TI  - Antiseptics under the Food, Drug, and Cosmetic Act.

PMID- 15433171
TI  - Present trends in methods of testing antiseptics.

PMID- 15433172
TI  - Halogens and their mode of action.

PMID- 15433173
TI  - Iodine as an antiseptic.

PMID- 15433174
TI  - Bacterial resistance.

PMID- 15433175
TI  - The relationship of concentration and germicidal efficiency of ethyl alcohol.

PMID- 15433176
TI  - Evaluation of mercurial compounds as antiseptics.

PMID- 15433177
TI  - Assay of antiseptics at different times after application to human skin.

PMID- 15433178
TI  - Mercurials as antiseptics.

PMID- 15433179
TI  - Prospects in the control of genetic disease.

PMID- 15433180
TI  - Brain abscess in relation to diseases of the ear, nose and throat.

PMID- 15433181
TI  - The blood and lymph pathways in the spermatic cord.

PMID- 15433182
TI  - Anaesthesia for cardiac surgery.

PMID- 15433183
TI  - An enquiry into the causation of peptic ulcers.

PMID- 15433184
TI  - Past presidents; Joseph Hodgson.

PMID- 15433185
TI  - Cervical arteriovenous anastomosis in treatment of mental retardation, convulsive
      disorders and cerebral spasticity.

PMID- 15433186
TI  - Considerations of bronchiogenic carcinoma.

PMID- 15433187
TI  - The role of the adrenal cortex in the postoperative retention of salt and water.

PMID- 15433188
TI  - Complete scalp avulsion: rational treatment; report of cases: experimental basis
      for production of free, hair bearing grafts from avulsed scalp itself.

PMID- 15433189
TI  - Arterial aneurysms.

PMID- 15433190
TI  - Sterilization of the intestinal tract by antibiotics and supplemental agents.

PMID- 15433191
TI  - Penicillin and streptomycin in the treatment of experimental Escherichia coli
      peritoneal infection.

PMID- 15433192
TI  - The conservative treatment of salpingitis complicating myomata uteri.

PMID- 15433193
TI  - A contribution to the surgical significance of aberrant hepatic ducts.

PMID- 15433194
TI  - Thrombophlebitis migrans; case report with autopsy and review of literature.

PMID- 15433195
TI  - Calcified intracerebral hematoma; case report and review of the literature.

PMID- 15433196
TI  - Tri-locular gastric diverticulum; treated by surgical extirpation through
      thoracoabdominal incision.

PMID- 15433197
TI  - Perforation of the gallbladder into the free peritoneal cavity with spontaneous
      healing.

PMID- 15433198
TI  - Cystic lymphangiomata of the greater omentum.

PMID- 15433199
TI  - Cholecystocholedochal fistula, an unusual form of internal biliary fistula.

PMID- 15433200
TI  - Plasmacytoma of the thyroid gland.

PMID- 15433201
TI  - Catheterization of the portal vein in man following porto-caval anastomosis.

PMID- 15433202
TI  - Ainhum (dactylolysis spontanea); a review of 10 cases.

PMID- 15433203
TI  - The training of surgeons for small communities.

PMID- 15433204
TI  - Congestive atelectasia complication of the intravenous infusion of fluids.

PMID- 15433205
TI  - Effect of analgesics and antispasmodics on common duct pressures.

PMID- 15433206
TI  - Further studies on factors influencing liver injury and liver repair.

PMID- 15433207
TI  - Postoperative salt retention and its relation to increased adrenal cortical
      function.

PMID- 15433208
TI  - Studies of combined vascular and neurologic injuries; the effect of somatic and
      sympathetic denervation upon the results of arterial ligation in the rat.

PMID- 15433209
TI  - The combination of sympathectomy and thiocyanates in the treatment of
      experimental and essential or high diastolic hypertension.

PMID- 15433210
TI  - Restoration of facial function by nerve anastomosis.

PMID- 15433211
TI  - Venous shunts in bilateral parasagittal meningioma.

PMID- 15433212
TI  - A study of the viability of autogenous frozen bone grafts by means of radioactive
      phosphorus.

PMID- 15433213
TI  - Results of treatment of subacromial bursitis in three hundred forty cases.

PMID- 15433214
TI  - Ac-globulin levels in thrombo-embolism.

PMID- 15433215
TI  - Agnogenic venous mesenteric thrombosis.

PMID- 15433216
TI  - Sudden and complete occlusion of the portal vein in the Macaca mulatta monkey.

PMID- 15433217
TI  - Valvulotomy for the relief of congenital valvular pulmonic stenosis with intact
      ventricular septum; report of 19 operations by the Brock method.

PMID- 15433218
TI  - Resection of the auricular appendages.

PMID- 15433219
TI  - General hypothermia for experimental intracardiac surgery; the use of
      electrophrenic respirations, an artificial pacemaker for cardiac standstill and
      radio-frequency rewarming in general hypothermia.

PMID- 15433220
TI  - Should total gastrectomy be employed in early carcinoma of the stomach;
      experience with 139 total gastrectomies.

PMID- 15433222
TI  - Medicine and law.

PMID- 15433221
TI  - The treatment of inguinal hernia in infants and children.

PMID- 15433223
TI  - Law and medicine.

PMID- 15433224
TI  - Cooperation of the professions in the administration of justice.

PMID- 15433225
TI  - Forensic medicine as a specialty.

PMID- 15433226
TI  - The expert witness.

PMID- 15433227
TI  - The Medical Practice Act, hospital law, the law of malpractice.

PMID- 15433229
TI  - The commitment and care of the mentally ill.

PMID- 15433228
TI  - The Narcotic Act and its relation to medical practice.

PMID- 15433230
TI  - Forensic psychiatry: limitations of psychological tests.

PMID- 15433231
TI  - An introduction to scientific crime detection.

PMID- 15433232
TI  - Medico-legal investigation of sudden death.

PMID- 15433233
TI  - The medico-legal autopsy.

PMID- 15433234
TI  - Toxicological experiences in the investigation of crime.

PMID- 15433235
TI  - Some of the practical aspects of physical evidence in the solution of crime.

PMID- 15433236
TI  - Significance of results obtained in blood grouping tests.

PMID- 15433237
TI  - The coroner's office and the law.

PMID- 15433238
TI  - Functions and practice of the autopsy surgeon in the coroner system.

PMID- 15433240
TI  - Medico-legal problems of workmen's compensation.

PMID- 15433239
TI  - Should the office of coroner be continued.

PMID- 15433241
TI  - Industrial poisons.

PMID- 15433242
TI  - The management of urinary tract infections.

PMID- 15433243
TI  - Management of refactory duodenal ulcer.

PMID- 15433244
TI  - Seminal vesiculitis, a disease entity sometimes confused with appendicitis.

PMID- 15433245
TI  - CLINICOPATHOLOGIC conference: cancer of the lung; cancer of the esophagus.

PMID- 15433246
TI  - Principles and teaching of differential diagnosis.

PMID- 15433247
TI  - [Preparation of new penicillins by biosynthesis].

PMID- 15433248
TI  - [Therapeutic use of penicillin].

PMID- 15433249
TI  - Some fundamental remarks on the polarographic determination of the catalase
      activity and the H2O2 production of bacteria.

PMID- 15433250
TI  - [Hemagglutination by smallpox virus; investigations of the passage of smallpox
      antihemagglutinins into the cerebrospinal fluid].

PMID- 15433252
TI  - [Rapid diagnosis of smallpox with Tieche's method].

PMID- 15433251
TI  - [Hemagglutination by smallpox virus; smallpox immunity in the newborn].

PMID- 15433253
TI  - On some spontaneous infections observed in mice; Corynebacterium kutscheri and
      Corynebacterium pseudotuberculosis.

PMID- 15433254
TI  - On some spontaneous infections observed in mice; the presence of Salmonella
      enteritidis (Gartner) in the peritoneal fluid.

PMID- 15433255
TI  - [Relationships between colicines and bacteriophages of the T 1-7 group].

PMID- 15433256
TI  - [Hemisporosis].

PMID- 15433257
TI  - [Bloch-Sulzberger's incontinentia pigmenti].

PMID- 15433258
TI  - [Collateral effects of penicillin].

PMID- 15433259
TI  - [Syndrome of (lupus) erythematodes acutus].

PMID- 15433260
TI  - [Indurative tuberculosis of the skin with clinical aspect of Besnier-Boeck
      Schaumann disease].

PMID- 15433261
TI  - [Syndrome similar to Vogt-Koyanagi's and Franzeschetti-Zwahlen mandibulofacial
      dysostosis].

PMID- 15433262
TI  - [Clinical manifestations of the Sanarelli-Shwartzman phenomenon in dermatology;
      acute febrile pemphigus and related diseases, and postoperative gangrene as
      manifestations of the Sanarelli-Shwartzman phenomenon].

PMID- 15433263
TI  - [Mathematicostatistical evaluation of different methods in the treatment of
      pemphigus, with special reference to germanin and to ulrone combined with focal
      disinfection].

PMID- 15433264
TI  - [Behavior of the leukocytes following injection of salvarsan].

PMID- 15433265
TI  - [Histogenesis of Kaposi's angiomatosis].

PMID- 15433266
TI  - [Investigation of the arterenol content of human and animal adrenals].

PMID- 15433267
TI  - [Effect of alcohols upon the enzymatic decomposition of tyramine].

PMID- 15433268
TI  - [Adrenolytic effect of d1-1-(4-hydroxyphenyl)-1-hydroxy-2-butylaminoethane].

PMID- 15433269
TI  - [Relationship between Vogt's intestinal extract substance and von Euler and
      Gaddum's P substance].

PMID- 15433270
TI  - [The hemoglobin-chlorate reaction].

PMID- 15433271
TI  - [Pathology of the erythrocytes; modifications of immature erythrocytes in primary
      hemolytic jaundice due to experimental nitrite poisoning].

PMID- 15433272
TI  - [Effect of central analeptics and sympathicomimetics upon the Bezold-Jarisch
      reflex].

PMID- 15433273
TI  - [Effect of nitrites upon human erythrocytes].

PMID- 15433274
TI  - [Effect of Gix, a commercial insecticide, upon rats and mice].

PMID- 15433275
TI  - [Relationship between Vogt's intestinal extract substance and von Euler and
      Gaddum's P substance].

PMID- 15433276
TI  - [Effect of diurnal rhythm upon glycogenesis in the liver, heart and body
      musculature following the administration of dextrose and ivert sugars].

PMID- 15433277
TI  - [Effect of the protracted administration of increasing excessive doses of veritol
      (beta-[p-oxyphenyl-] isopropylmethylamine) in animal experiments].

PMID- 15433278
TI  - [Synergistic action of barium ions and acetylcholine].

PMID- 15433279
TI  - [Suitability of the insecticide hexachlorocyclohexane as an oxyuricide].

PMID- 15433280
TI  - [Pharmacology of cancerogenic substances; experiments with aniline].

PMID- 15433281
TI  - [Method of studying the pharmacology of human sweat glands].

PMID- 15433282
TI  - [Bleeding time and the effect of hemostyptics].

PMID- 15433283
TI  - [Problem of fatal pulmonary embolism].

PMID- 15433284
TI  - [Action of cholinergic substances; effect of eserine and prostigmine on the
      isolated frog ventricle].

PMID- 15433285
TI  - [Fermental oxidation of adrenalin in human serum].

PMID- 15433286
TI  - [Phosphorylation in denervated muscle].

PMID- 15433287
TI  - [Etiology of muscular asthenia in adrenocortical insufficiency; investigations of
      the isolated diaphragm of normal and adrenalectomized rats subject to varying
      extracellular concentrations of sodium, potassium, calcium and glucose].

PMID- 15433288
TI  - [Modifications of serum protein in the rat following benzene poisoning and
      roentgen irradiation].

PMID- 15433289
TI  - [Pharmacology of serium; its effect upon the blood picture of the rabbit].

PMID- 15433290
TI  - [Renal circulation in polyuria in the rat].

PMID- 15433291
TI  - [Modifications produced by adrenalin in the first and second phases of the
      ventricular systole, and in the circulation volume in the normal man].

PMID- 15433292
TI  - [Effect of dinitrocresol and thiouracil upon cell metabolism].

PMID- 15433293
TI  - [A new method in the study of the analgetic mechanism].

PMID- 15433294
TI  - [Effect of several derivatives of polamidon, 2-dimethylamino-4,4-diphenylheptan-5
      one].

PMID- 15433295
TI  - [Kinetics of hemoglobin formation; in vivo formation of hemoglobin by
      nitrosobenzene].

PMID- 15433296
TI  - [Effect of novocain upon the susceptibility of the central nervous system to
      electroshock].

PMID- 15433297
TI  - [Bacteriology of the uterine lochia during puerperium following obstetric
      operations].

PMID- 15433298
TI  - [Results of a histologic study of uterine innervation].

PMID- 15433299
TI  - [Clinical significance of prolonged menstrual desquamation and retarded
      regeneration of the uterine mucosa].

PMID- 15433300
TI  - [Etiology of so-called one-day puerperal fever; retention of the lochia without
      endometritis as a cause of puerperal fever].

PMID- 15433301
TI  - [Vaginal metastases of renal cancer; pathology and clinical aspects].

PMID- 15433302
TI  - [Results of fluorescent-microscopic examination for determination of the tubercle
      bacillus in tuberculosis of the female genitalia, with three unusual case
      reports].

PMID- 15433303
TI  - [Hemorrhage from the genitals during the menopause, with special reference to
      glandular cystic hyperplasia].

PMID- 15433304
TI  - [Karl Wilhelm Jotten -- to the anniversary].

PMID- 15433305
TI  - [Bibliography of K. W. Jotten].

PMID- 15433306
TI  - [Development of legislation relative to pneumoconiosis in Germany and abroad,
      with a survey of German legislation relative to occupational disease].

PMID- 15433307
TI  - [Industrial medicine in the work of Jean Paul Friedrich Richter].

PMID- 15433308
TI  - [Inclusion bodies in the vacuoles of liver cells, especially in epidemic
      jaundice].

PMID- 15433309
TI  - [Catgut].

PMID- 15433310
TI  - [Mass poisoning by a so-called floor cleaner as a result of gross negligence].

PMID- 15433311
TI  - [Necessity for an effective separation of the supply systems of water for
      industrial use and for consumption on premises with several water supplies;
      report of several cases of poisoning as a result of the reflux of waste water
      polluted by carbide into the conduction system of the public water works].

PMID- 15433312
TI  - [Injuries to health resulting from the use of fire extinguishers, particularly
      those containing methyl bromide].

PMID- 15433313
TI  - [Present status of sero-diagnosis of syphilis].

PMID- 15433314
TI  - [Coniophagocytosis and its significance in the etiology of silicosis;
      experimental studies of exudate cells and tissue cultures].

PMID- 15433315
TI  - [Observations and experiments on the sericite theory; pneumoconiosis caused by
      quartz in association with other dusts].

PMID- 15433316
TI  - [Present status of disinfection].

PMID- 15433317
TI  - [Statistical study of occupational cancer among textile workers].

PMID- 15433318
TI  - [Recent investigations on the pharmacological and bacteriostatic effect of
      streptomycin].

PMID- 15433319
TI  - [Periarteritis nodosa in children].

PMID- 15433320
TI  - [Prognosis of acute diffuse glomerulonephritis in children].

PMID- 15433321
TI  - [Periston in the treatment of toxic states in diphtheria, scarlet fever, and
      dysentery].

PMID- 15433322
TI  - [Comparative determinations of cerebrospinal fluid protein and their diagnostic
      significance].

PMID- 15433323
TI  - [Experiences with Muller and Romginer's lactose- and fat-enriched milk].

PMID- 15433324
TI  - [Experiences in the treatment of alimentary intoxication].

PMID- 15433325
TI  - [Differential diagnosis of serous meningitis in childhood, with case reports].

PMID- 15433326
TI  - [Double infection of leptomeninges with pneumococci and Pfeiffer's influenza
      baccillus in infancy].

PMID- 15433327
TI  - [Attempted suicide in an eleven year old boy].

PMID- 15433328
TI  - [Observations on so-called ascariasis in childhood based on 1100 cases observed
      in the consultation clinic; with a note on the successful treatment of
      panmyelopathy in children].

PMID- 15433329
TI  - [Value of blood sedimentation rate in the diagnosis of tuberculosis of the
      respiratory organs in children].

PMID- 15433330
TI  - [Case reports, including one postvaccinal, of polyradiculoneuritis (Guillain
      Barre syndrome in infancy].

PMID- 15433331
TI  - [Mandibular actinomycosis in childhood].

PMID- 15433332
TI  - [Gastric secretion of hydrochloric acid in children with ascariasis].

PMID- 15433333
TI  - [Epidemiologic and clinical aspects of scarlet fever].

PMID- 15433334
TI  - [Investigations on the effect of encephalography upon capillary resistance of the
      skin in children].

PMID- 15433335
TI  - [Treatment of thoracogenous brain abscess].

PMID- 15433336
TI  - [Experimental studies on longitudinal epiphyseal growth of bone under pressure].

PMID- 15433338
TI  - [Idiopathic spontaneous pneumothorax].

PMID- 15433337
TI  - [Segmental ultraviolet irritation of the skin as an aid in the topical diagnosis
      of an affected organ].

PMID- 15433339
TI  - [Effect of cyclopropane anesthesia upon blood circulation].

PMID- 15433340
TI  - [Anesthesia in intrathoracic and transthoracic surgery].

PMID- 15433342
TI  - [Thoughts on the development of surgery].

PMID- 15433341
TI  - [Ferdinand Sauerbruch on his 75th birthday].

PMID- 15433343
TI  - [Twenty years of carcinoma therapy].

PMID- 15433344
TI  - [Loss of both hands].

PMID- 15433345
TI  - [Cardiac failure and its treatment].

PMID- 15433346
TI  - [The problem of blood protein in surgery].

PMID- 15433347
TI  - [Anatomic and functional studies of intervertebral disk hernia].

PMID- 15433348
TI  - [Injurious effects of thorotrast injection].

PMID- 15433349
TI  - [Surgical therapy of intrathoracic diverticula of the esophagus].

PMID- 15433350
TI  - [Progress in our knowledge of the general effect of surgery upon the body;
      problem of the corticodiencephalon-hormonal mechanism].

PMID- 15433351
TI  - [Origin of subdural hydroma].

PMID- 15433353
TI  - [Segmental resection in surgery of bronchiectasis].

PMID- 15433352
TI  - [Unusual mediastinal tumors; surgical observations].

PMID- 15433354
TI  - [Unusual diseases of the gallbladder; acute pneumocholecystitis and total
      necrosis with spontaneous amputation].

PMID- 15433355
TI  - [Surgical therapy of scoliosis].

PMID- 15433356
TI  - [Dangers of combined evipalscophedal anesthesia].

PMID- 15433357
TI  - [Pheochromocytoma and its relation to adrenocortical function; with report of
      bilateral pheochromocytoma in childhood].

PMID- 15433358
TI  - [Differential diagnosis of suprasellar calcification shadows].

PMID- 15433359
TI  - [Unusual intrathoracic cysts related to the digestive tract].

PMID- 15433360
TI  - [Load-tolerance studies of the elasticity of the Achilles tendon].

PMID- 15433361
TI  - [Allergic reactions of burned skin in the course of healing, with special
      reference to local hyperemia and traumatic hypotension].

PMID- 15433362
TI  - [Wilhelm Lange-Eichbaum].

PMID- 15433363
TI  - [Spinal ang ioma racemosum venosum].

PMID- 15433364
TI  - [The problem of amnesia following electroshock therapy].

PMID- 15433365
TI  - [Problem of injury to cerebral tissue in shock therapy].

PMID- 15433366
TI  - [Application of certain physical and chemical concepts to explanation of
      morphological findings in the central nervous system; structural elements and
      denaturation].

PMID- 15433367
TI  - [Spasmodic diathesis and constitution].

PMID- 15433368
TI  - [A simple index for evaluation of alpha-radiation in electroencephalography].

PMID- 15433369
TI  - [Constitutional modifications following shock therapy].

PMID- 15433370
TI  - [Clinical and pathological aspects of primary acute hemorrhagic encephalitis].

PMID- 15433371
TI  - [The pattern of epilepsy in the Rorschach test].

PMID- 15433372
TI  - [Diffuse symmetric calcification in a syndrome including microcephaly and
      meningoencephalitis].

PMID- 15433373
TI  - [Cerebral hemangioma; telangiectasis, cavernoma Sturge-Weber disease].

PMID- 15433374
TI  - [Statistical survey of 248 intracranial tumors].

PMID- 15433375
TI  - [The hereditary form of Creutzfeldt-Jakob disease (the Backer family)].

PMID- 15433376
TI  - [Research on the submicroscopic structure of the peritrophic membrane of the
      medium intestine in certain insects].

PMID- 15433377
TI  - [Seasonal cycle of the endocrine glands in hibernating animals].

PMID- 15433378
TI  - [Sacro-coccygeal plexus].

PMID- 15433380
TI  - [Tuberculous lupus].

PMID- 15433379
TI  - [Study of a spontaneous freemartin in ruminants].

PMID- 15433382
TI  - [The history of social service].

PMID- 15433381
TI  - [Health of students].

PMID- 15433383
TI  - [Medicolegal diagnosis of alcoholic intoxication].

PMID- 15433384
TI  - [The notion of low risk in the reform of sickness-disability insurance].

PMID- 15433385
TI  - [Preventive medicine, a year of periodic physical examinations].

PMID- 15433386
TI  - [A rapid procedure for determination of the arithmetical mean and mean quadratic
      deviation of a series of measurements, as well as the coefficients of
      correlation].

PMID- 15433387
TI  - [The history of the sciences of man].

PMID- 15433388
TI  - [The notion of low risk in the reform of sickness-disability insurance].

PMID- 15433389
TI  - [Preventive medicine, a year of periodic physical examinations].

PMID- 15433390
TI  - [The history of the sciences of man].

PMID- 15433391
TI  - Lesions of the scalp in certain scaly dermatoses; histologic study.

PMID- 15433392
TI  - Comparison of muscle biopsies and bone marrow examinations in dermatomyositis and
      lupus erythematosus.

PMID- 15433393
TI  - Poikiloderma vasculare atrophicans; report of a case due to exposure to cold.

PMID- 15433394
TI  - Beryllium window radiations for superficial therapy.

PMID- 15433395
TI  - Absorption of roentgen rays with use of a beryllium window tube.

PMID- 15433396
TI  - Outcome of pregnancies of women treated with aqueous penicillin for early
      infectious syphilis; prevention of parental syphilis.

PMID- 15433397
TI  - Shielding of skin against roentgen radiation by plastic compounds.

PMID- 15433398
TI  - Dermatologic aspects of insect repellents and toxicants.

PMID- 15433399
TI  - Streptomycin treatment of granuloma inguinale.

PMID- 15433400
TI  - Effect of yeast extract on Microsporum audouini and Microsporum canis.

PMID- 15433401
TI  - Chemosurgical treatment of melanoma; a microscopically controlled method of
      excision.

PMID- 15433402
TI  - Peculiar deformity of hands occurring in epidermolysis bullosa.

PMID- 15433403
TI  - Treatment of onychomycosis with ammoniacal silver nitrate solution.

PMID- 15433404
TI  - Therapeutic value of chloramphenicol in a group of dermatoses of established or
      questionable virus etiology.

PMID- 15433405
TI  - Blood vessels of the skin in chronic venous insufficiency; clinical and
      pathologic study.

PMID- 15433406
TI  - Atypical keratosis pilaris.

PMID- 15433407
TI  - Hypoallergenic penicillin in oil.

PMID- 15433409
TI  - Pyoderma gangrenosum.

PMID- 15433408
TI  - Influence of grenz rays on histamine-induced manifestations.

PMID- 15433410
TI  - Calcinosis cutis.

PMID- 15433411
TI  - Cushing's syndrome and hidradenitis suppurativa.

PMID- 15433412
TI  - Torulosis.

PMID- 15433414
TI  - Dermatitis herpetiformis.

PMID- 15433413
TI  - Systemic blastomycosis.

PMID- 15433415
TI  - Dermatitis herpetiformis; diabetes mellitus.

PMID- 15433416
TI  - Lymphoblastoma cutis.

PMID- 15433417
TI  - Scleroderma.

PMID- 15433418
TI  - A case for diagnosis: lichen spinulosus?

PMID- 15433419
TI  - Poikilodermatomyositis.

PMID- 15433420
TI  - A case for diagnosis: lichenoid sarcoid, leprosy?

PMID- 15433421
TI  - Lupus erythematosus; neurosyphilis.

PMID- 15433422
TI  - A case for diagnosis: pemphigus?

PMID- 15433423
TI  - Scientific work of Paul Gerson Unna.

PMID- 15433424
TI  - Treatment of senile keratoses with podophyllin.

PMID- 15433425
TI  - Decadent descriptions in dermatology.

PMID- 15433426
TI  - Sponge biopsy in the diagnosis of cancer of the skin and oral mucosa.

PMID- 15433427
TI  - Reiter's disease: a case successfully treated with aureomycin.

PMID- 15433428
TI  - Atypical blue nevus; report of a case.

PMID- 15433429
TI  - Eczema of the hands from wooden-handled objects.

PMID- 15433430
TI  - Osteoma cutis as a result of severe acne vulgaris of long duration.

PMID- 15433431
TI  - Cryotherapy: a new method.

PMID- 15433432
TI  - Removal of sebaceous cysts by electrosurgical means.

PMID- 15433433
TI  - Induced sensitization to certified dye; hypersensitivity manifested on sixth
      exposure to commercial patch testing solutions.

PMID- 15433434
TI  - Treatment of dermatitis herpetiformis resistant to usual therapy.

PMID- 15433435
TI  - American leishmaniasis; report of a case with unusual mucocutaneous lesions.

PMID- 15433436
TI  - Large spores (macroconidia, fuseaux) of Microsporum audouini in vivo; report of a
      case.

PMID- 15433437
TI  - Brittle nails: a cause.

PMID- 15433438
TI  - Benign course of dermatophytosis due to combined infection with Epidermophyton
      floccosum and Trichophyton rubrum; report of a case.

PMID- 15433439
TI  - Postradiation comedos.

PMID- 15433440
TI  - Acne vulgaris: a comparison of local remedies.

PMID- 15433441
TI  - Ehlers-Danlos syndrome: report of a case.

PMID- 15433442
TI  - Erythroderma and erythrodermia; a note on nomenclature.

PMID- 15433443
TI  - A case for diagnosis (perifolliculitis capitis abscedens et suffodiens?).

PMID- 15433444
TI  - Fox-Fordyce disease uninfluenced by treatment with roentgen radiation and topical
      measures.

PMID- 15433445
TI  - A case for diagnosis (ganglioneuroma? histiocytoma? myoblastoma?).

PMID- 15433446
TI  - Generalized granuloma annulare.

PMID- 15433448
TI  - Lichen sclerosus et atrophicus of breasts and anogenital regions.

PMID- 15433447
TI  - Dermatitis of seven years' duration originally due to cement.

PMID- 15433449
TI  - Mycosis fungoides.

PMID- 15433450
TI  - Moniliasis: infectious eczematoid dermatitis?

PMID- 15433451
TI  - Malignant melanoma.

PMID- 15433452
TI  - Lupus vulgaris.

PMID- 15433453
TI  - Urticaria pigmentosa.

PMID- 15433454
TI  - Cheilitis exfoliativa.

PMID- 15433455
TI  - Eosinophilic granuloma of the skin.

PMID- 15433456
TI  - Pemphigus vegetans: remission after treatment with aureomycin.

PMID- 15433457
TI  - Localized hyperhidrosis of the forehead.

PMID- 15433458
TI  - Osteoma cutis.

PMID- 15433459
TI  - Herpes gestationis (post partum).

PMID- 15433460
TI  - [Five cases of retrolental fibroplasia in premature infants].

PMID- 15433461
TI  - [Craniofacial dysostosis with displacement of the crystalline lens].

PMID- 15433462
TI  - [Whooping cough encephalitis and streptomycin].

PMID- 15433463
TI  - [Value of urologic examination in the diagnosis of perinephritic abscess in
      infancy].

PMID- 15433464
TI  - [Farina malted by a new technic; action on growth of hypotrophic infants].

PMID- 15433465
TI  - [Intra-cranial hypertension in newborn].

PMID- 15433466
TI  - [Results obtained in a climatotherapy station by postural drainage for dilatation
      of the bronchi in children].

PMID- 15433467
TI  - [Attempted neurosurgical treatment of achondroplasia].

PMID- 15433468
TI  - [Grippe encephalitis treated by aureomycin; cure].

PMID- 15433469
TI  - [Influence of inapparent infection on a rat fetus].

PMID- 15433470
TI  - [Two cases of congenital malignant tumors in children].

PMID- 15433471
TI  - [Acute suppurative mediastinitis after traumatic perforation of the esophagus in
      a 28 month old infant; surgery; cure].

PMID- 15433472
TI  - [Ollier's dyschondroplasia in an infant].

PMID- 15433473
TI  - [Two atypical cases of jaundice of newborn due to maternal iso-immunization
      without erythroblastemia, treated by exchange transfusion].

PMID- 15433474
TI  - [Temporary high eosinophilia in a 10 year old child].

PMID- 15433475
TI  - [Two cases of tetanus after application of plaster casts in children].

PMID- 15433476
TI  - [Autochthonous malaria of an infant due to injection of maternal blood].

PMID- 15433477
TI  - [Treatment of acrodynia by electro-shock].

PMID- 15433478
TI  - [Not Available].

PMID- 15433479
TI  - [Case of dementia after streptomycin therapy of tuberculous meningitis].

PMID- 15433480
TI  - [Surgical therapy of encysted constrictive pericarditis].

PMID- 15433481
TI  - [Therapeutic value of cisternotomy for grave mental defectives].

PMID- 15433482
TI  - [Arnold-Chiari syndrome; study of the associated malformations].

PMID- 15433483
TI  - [Advisability and technic of anti-typhoid vaccinations in schools].

PMID- 15433484
TI  - [Three cases of gangrene of the extremities of the infant].

PMID- 15433485
TI  - [A special form of infantile polyarthritis; Wissler-Fanconi syndrome].

PMID- 15433486
TI  - [Methionine in the treatment of lipogenic dyshepatia of the child].

PMID- 15433487
TI  - [A disease of the Moslem infant; weaning edema; pathogenic assay].

PMID- 15433488
TI  - Acute inhalation toxicity of beryllium; four definitive studies of beryllium
      sulfate at exposure concentrations of 100, 50, 10, and 1 mg. per cubic meter.

PMID- 15433489
TI  - Acute inhalation toxicity of beryllium; the enhancing effect of the inhalation of
      hydrogen fluoride vapor on beryllium sulfate poisoning in animals.

PMID- 15433490
TI  - Rehabilitation: the third phase of medicine.

PMID- 15433491
TI  - Arsine poisoning; epidemiologic studies of an outbreak following exposure to
      gases from metallic dross.

PMID- 15433492
TI  - Arsine poisoning; a study of 13 cases.

PMID- 15433493
TI  - Relationships between the industrial medical department and the private
      physician.

PMID- 15433494
TI  - Injuries following continued administration of cadmium; preliminary report of a
      clinical and experimental study.

PMID- 15433495
TI  - Potential sources of error in blood lead determinations due to different methods
      of blood sampling.

PMID- 15433496
TI  - Peritoneal reaction to injected fused (spherical) and unfused (spiculate) quartz;
      pathologic studies.

PMID- 15433497
TI  - The toxic properties of xylidine and monomethylaniline; II The comparative
      toxicity of xylidine (C6H3[CH3]2NH2) and monomethylaniline (C6H5N[H]CH3) inhaled
      as vapor in air by animals.

PMID- 15433498
TI  - The industrial employee with myocardial infarction; his ability to return to
      work.

PMID- 15433499
TI  - Toxicologic studies on certain commercia silicones; I. Two year dietary feeding
      of "DC Antifoam A" to rats.

PMID- 15433500
TI  - Evidence of systemic effect of tetryl; with summary of available literature.

PMID- 15433501
TI  - An electrostatic precipitator for the continuous sampling of sulfuric acid
      aerosols and other air-borne particulate electrolytes.

PMID- 15433502
TI  - Air-ventilated clothing for wear in extremely hot environments.

PMID- 15433503
TI  - INDISCRIMINATE administration of vitamins to workers in industry.

PMID- 15433504
TI  - NINTH Annual Congress on Industrial Health; report of the panel on environment
      hygiene; Drake Hotel, Chicago, Jan. 18-19, 1949.

PMID- 15433505
TI  - Pharmacologic studies of furfuryl alcohol.

PMID- 15433506
TI  - Parathion inhibition of cholinesterase.

PMID- 15433507
TI  - Acute toxicity of zirconium, columbium, strontium, lanthanum, cesium, tantalum
      and yttrium.

PMID- 15433508
TI  - Prolonged inhalation of cadmium.

PMID- 15433509
TI  - Incidence of cancer in the carbon black industry.

PMID- 15433510
TI  - Toxicity of cadmium sulfide and cadmium sulfoselenide pigments.

PMID- 15433511
TI  - Absorption and elimination of inhaled benzene in man.

PMID- 15433512
TI  - The Chronic Illness Commission; its relation to industrial medicine.

PMID- 15433513
TI  - We need to be unified.

PMID- 15433514
TI  - Pulmonary manifestions of gasoline intoxication.

PMID- 15433515
TI  - Acute toxicity of inhaled beryllium; observations correlating toxicity with the
      physicochemical properties of beryllium oxide dust.

PMID- 15433516
TI  - Rapid method for the determination of aromatic hydrocarbons in air.

PMID- 15433517
TI  - Compensation for lung changes due to the inhalation of silica dust.

PMID- 15433518
TI  - Miniature work situations as a research tool, with special reference to the study
      of physiologic stresses.

PMID- 15433519
TI  - Industrial health in the undergraduate medical curriculum.

PMID- 15433520
TI  - Ionizing radiation materials as air pollutants.

PMID- 15433521
TI  - Effects of air pollution on oral structures.

PMID- 15433522
TI  - Effects of so-called inert dusts.

PMID- 15433523
TI  - Selling industrial medicine to the medical profession.

PMID- 15433524
TI  - Arsine poisoning in the smelting and refining industry.

PMID- 15433525
TI  - Coproporphyrinuria as an index of lead absorption.

PMID- 15433526
TI  - Distribution and fate of cadmium in the animal body.

PMID- 15433527
TI  - Some industrial aspects of aging.

PMID- 15433528
TI  - Tripelennamine hydrochloride in the treatment of the common cold.

PMID- 15433529
TI  - A management approach to problems of individual adjustment.

PMID- 15433530
TI  - SYMPOSIUM on prepayment health plans for industrial workers.

PMID- 15433532
TI  - Blue Shield prepayment health plans.

PMID- 15433531
TI  - Medical care for industrial employees.

PMID- 15433533
TI  - Blue Cross plans.

PMID- 15433534
TI  - Union plans.

PMID- 15433535
TI  - The medical, health and hospital program of the U. M. W. A. Welfare and
      Retirement Fund.

PMID- 15433536
TI  - New joint contributory group insurance program for Weirton Steel employees.

PMID- 15433537
TI  - The Medical Department of the American Cast Iron Pipe Company.

PMID- 15433538
TI  - Essential principles of private insurance prepayment health plans for industrial
      workers.

PMID- 15433539
TI  - The private insurance company viewpoint re: essential principles of current
      medical care plans for industrial workers.

PMID- 15433540
TI  - Some requisites to making LD50's from different laboratories comparable.

PMID- 15433541
TI  - Anthracosilicosis in bituminous coal miners; clinical and pathological
      manifestations.

PMID- 15433542
TI  - Pharmacologic tools in the study of the mechanism of uranium poisoning.

PMID- 15433543
TI  - Preventive aspects of occupational dermatoses.

PMID- 15433544
TI  - Environmental cancer hazards caused by industrial air pollution; introductory
      comment to the discussion.

PMID- 15433545
TI  - Respiratory tract allergic effects from chemical air pollution.

PMID- 15433546
TI  - Acute and chronic toxicity of some halogenated derivatives of methane and ethane.

PMID- 15433547
TI  - Toxicity of the tetrachlorodifluoroethanes.

PMID- 15433548
TI  - The toxicity of sulfur hexafluoride.

PMID- 15433549
TI  - The toxicity of sulfur pentafluoride.

PMID- 15433550
TI  - [Granulodiagnosis of tuberculosis according to one thousand observed cases].

PMID- 15433551
TI  - [Comparative evaluation of antituberculous vaccination by scarification and
      subcutaneous inoculation].

PMID- 15433552
TI  - [Bacteriological study of vibrios isolated during the pilgrimage to Mecca].

PMID- 15433553
TI  - [Preparation and utilization of a crystal violet vaccine against swine plague].

PMID- 15433554
TI  - [Localization of antibodies in the antiserum of the swine plague].

PMID- 15433555
TI  - [Phlebotomes of the island of Zembra. (Tunisia)].

PMID- 15433556
TI  - [Study of scorpions; scorpions of North Africa].

PMID- 15433557
TI  - [Study of scorpions; biogeography of the scorpions of North Africa. (Berbera and
      Sahara)].

PMID- 15433558
TI  - [Report on the functioning of the Institute Pasteur d'Algerie in 1949].

PMID- 15433559
TI  - [Inorganic constituents of blood plasma in Anodonta cygnea L. in state of
      inanition].

PMID- 15433560
TI  - [Effect of frequency of excitation on tetanic contraction of the muscle].

PMID- 15433561
TI  - [Study of the respiratory movements of the bee by means of optic registration].

PMID- 15433562
TI  - [Desensibilization to potassium by local anesthesia].

PMID- 15433563
TI  - Inhibitory action of carbon dioxide on experimental convulsions; experiments on
      cryoepilepsy in the frog; mechanism of the inhibitory action of carbon dioxide on
      convulsions.

PMID- 15433564
TI  - [Criticism of the methods of mineralization of bones].

PMID- 15433565
TI  - [Oscillographic study of the nerve response of the frog and its post-reaction
      restoration in various nutritional states of the animal].

PMID- 15433566
TI  - [Cortical repercussions of the reaction of the primary acoustic area: the
      secondary acoustic area].

PMID- 15433567
TI  - [Effect of a transplanted kidney on the acid-base equilibrium of a nephrectomized
      dog].

PMID- 15433568
TI  - [The influence of the pH of the cerebrospinal fluid on respiration].

PMID- 15433569
TI  - [Ampullar potentials and the process of excitation of the semicircular canals].

PMID- 15433570
TI  - [Influence of thyroid hormones on the reaction of mammalian striated muscle to
      adrenalin].

PMID- 15433571
TI  - [Study of the H-G factor of the pancreas].

PMID- 15433572
TI  - [Central action of muscular proprioceptors of the frog].

PMID- 15433573
TI  - [Vasomotor reactions of mesenteric arteries].

PMID- 15433574
TI  - [Specificity of the action of CO2 on the respiratory center].

PMID- 15433575
TI  - [Ionoregulation of the internal medium of Anodonta in concentrated external
      media].

PMID- 15433576
TI  - [Prophylaxis of diabetes].

PMID- 15433577
TI  - [Protein metabolism in gastric ulcer; results of determination of proteins of the
      stomach wall].

PMID- 15433578
TI  - [Azotemia due to chloropenia caused by a voluminous biliary calculus having
      migrated into the pyloric antrum].

PMID- 15433579
TI  - [Nine cases of a hemorrhagic form of diverticulitis of the colon].

PMID- 15433580
TI  - [Sensitivity of Enterobacteriaceae to chloromycetin].

PMID- 15433581
TI  - [The phase contrast microscope in intestinal parasitology].

PMID- 15433582
TI  - [Chronic jaundice as a late sequel of infectious mononucleosis; mesenchymatous
      hepatitis periarterial hepatic sympathectomy; cure].

PMID- 15433583
TI  - [Case of hemorrhagic rectocolitis treated by left iliac anus].

PMID- 15433584
TI  - [Inflammatory stenosis of the common bile duct and lithiasis of the gallbladder;
      cholecystectomy, hepatico-duodenostomy, cure].

PMID- 15433585
TI  - [Acute pancreatitis after cholangiography].

PMID- 15433586
TI  - [Dysphagia and diverticula of the upper esophagus].

PMID- 15433587
TI  - [Hemorrhage from a tumor of the small intestine].

PMID- 15433588
TI  - [Case of epithelioma of the small intestine; clinical and radiological
      considerations].

PMID- 15433589
TI  - [Perforating form of amebic abscess of the liver].

PMID- 15433590
TI  - [Giant diverticulum of the thoracic esophagus simulating an encysted
      hydropneumothorax, with megaesophagus].

PMID- 15433591
TI  - [Recto-vaginal perforation; complication of hemorrhagic recto-colitis].

PMID- 15433592
TI  - [The future of gastrectomized patients].

PMID- 15433593
TI  - [Right hypertrophic ulcerative colitis; subocclusion revealed by radiographic
      examination of the small intestine].

PMID- 15433594
TI  - [Some normal and pathological radiological aspects of the cardia].

PMID- 15433595
TI  - [Digestivo-digestive or inter-digestive relationships and syndromes].

PMID- 15433596
TI  - [The duodenal diverticulum is often only an accessory].

PMID- 15433597
TI  - [Case of pyloric stenosis of vesicular origin].

PMID- 15433598
TI  - [Colloid ulceriform juxtapyloric cancer; preoperative diagnosis; gastrectomy;
      cure].

PMID- 15433599
TI  - [Radiologic exploration of the small intestine; value and indications; elementary
      semeiology of enteritis].

PMID- 15433600
TI  - [Cancer of the tail of the pancreas simulating Banti's syndrome].

PMID- 15433601
TI  - [Ulcer of the duodenal bulb and mobile initial duodenum].

PMID- 15433602
TI  - [Ulcer or gastric syphilis?].

PMID- 15433603
TI  - [Dissecting aneurysms and dissecting medianecrosis of the aorta].

PMID- 15433604
TI  - [Pulmonary hemangioma; diagnosis by angiocardiography and surgery].

PMID- 15433605
TI  - [Not Available].

PMID- 15433606
TI  - [Cardiac manifestations in sulfonamide intolerance].

PMID- 15433607
TI  - [Cobalt in cardiovascular experimentation and therapy].

PMID- 15433608
TI  - [Chronic cor pulmonale and premonitory syndrome; statistical study of 34 personal
      cases].

PMID- 15433609
TI  - [Nodule of temporal arteritis due to embolic process].

PMID- 15433610
TI  - [Congenital arteriovenous fistula between the occipital artery and the internal
      jugular].

PMID- 15433611
TI  - [Organization of the fight against silicosis in Italy].

PMID- 15433612
TI  - [The human factor and industrial accidents].

PMID- 15433613
TI  - [Study of the excitability of respiratory centers and sympathetic vaso-pulmonary
      centers in silicotics].

PMID- 15433614
TI  - [Case of fatal erythroblastic anemia in a worker exposed to benzol].

PMID- 15433615
TI  - [Professional pneumopathy due to irritating gas; diagnostic problems].

PMID- 15433617
TI  - [Pulmonary siderosis].

PMID- 15433616
TI  - [Professional diseases and balneotherapy].

PMID- 15433618
TI  - [Case of acute poisoning by thallium nitrate].

PMID- 15433619
TI  - [Organization of industrial medicine in small businesses].

PMID- 15433620
TI  - [Social service in small industries].

PMID- 15433621
TI  - [Estimation of work capacity in silicosis by spirometric readings during effort].

PMID- 15433622
TI  - [Dangerous therapeutics of infirmaries].

PMID- 15433623
TI  - [Hemolytic phenomena due to benzene and its homologues].

PMID- 15433624
TI  - [Critical study of function tests in silicosis].

PMID- 15433625
TI  - [Case of industrial poisoning by Duboisia leichardti powder].

PMID- 15433626
TI  - [Wetting agents and industrial medicine].

PMID- 15433627
TI  - [Simple method of estimating dangerous quantities of X rays].

PMID- 15433628
TI  - [Statistical study of the results obtained by carbogen therapy in chronic carbon
      monoxide poisoning].

PMID- 15433629
TI  - [Porphyrinuria in lead poisoning; simplified determination].

PMID- 15433630
TI  - [General health level in an industrial printshop with about 2000 workers].

PMID- 15433631
TI  - [Benzene hazard in the tanning industry].

PMID- 15433632
TI  - [Case of cancer of the larynx in a worker exposed to arsenical dusts].

PMID- 15433633
TI  - [Socialized climatotherapy; clinical basis].

PMID- 15433634
TI  - [Endemic Typho-paratyphoid in Marseill during 1949].

PMID- 15433635
TI  - [Geographic habitat and schools; medical examination of school children of urban
      and rural zones of the region of Chartres].

PMID- 15433636
TI  - Direct reorientation of behavior patterns in deep narcosis (narcoplexis).

PMID- 15433637
TI  - Recent contributions to the anatomy and physiology of the cerebellum.

PMID- 15433638
TI  - Focal electroencephalographic changes in unilateral electric convulsion therapy.

PMID- 15433639
TI  - Treatment of tumors of the pineal body; experience in a series of 22 cases.

PMID- 15433640
TI  - Nature of the schizophrenic process; a working hypothesis for therapy.

PMID- 15433641
TI  - Deaths associated with electric shock therapy; report of 3 cases.

PMID- 15433642
TI  - Hemiballism and its control by ablation of the motor cortex.

PMID- 15433643
TI  - Use of diphenhydramine in treatment of paralysis agitans.

PMID- 15433644
TI  - Effect of bilateral stellectomy on the cerebral circulation of man.

PMID- 15433645
TI  - Clinical experience with mephenesin ("tolserol"; myanesin) in treatment of
      hyperkinetic disorders, with special reference to postencephalitic paralysis
      agitans.

PMID- 15433647
TI  - A study of meningiomas occurring in a general hospital.

PMID- 15433646
TI  - Thymectomy in treatment of myasthenia gravis: report of 3 cases.

PMID- 15433648
TI  - Pallidothalamotomy in chorea.

PMID- 15433649
TI  - The physiologic basis of shock therapy.

PMID- 15433650
TI  - Nature of processes in the central nervous system in the psychoneuroses.

PMID- 15433651
TI  - Role of sympathetic and parasympathetic systems in reflex dilation of the pupil;
      pupillographic studies.

PMID- 15433652
TI  - Mutual role of sympathetic and parasympathetic in shaping of the pupillary reflex
      to light; pupillographic studies.

PMID- 15433653
TI  - Some data concerning the growth and development of the cerebral cortex in man;
      postnatal growth changes in the cortical surface area.

PMID- 15433654
TI  - Psychic function and the electroencephalogram.

PMID- 15433655
TI  - Myelomalacia secondary to dissecting aneurysm of the aorta.

PMID- 15433656
TI  - Manic psychosis in a case of parasagittal meningioma.

PMID- 15433657
TI  - Pleocytosis and meningeal signs in uremia; report on 62 cases.

PMID- 15433658
TI  - The psychiatrist in the general hospital.

PMID- 15433659
TI  - Electroencephalographic studies of the encephalopathies; report of a nonfatal
      case of arsenical "hemorrhagic encephalopathy" with serial EEG studies.

PMID- 15433660
TI  - Principles underlying the projective technics of personality measurement.

PMID- 15433661
TI  - Drawings as objective criteria for neurotic conflict and their change during
      psychoanalysis.

PMID- 15433662
TI  - [Diffraction phenomena of the eye and experimental study of comparison].

PMID- 15433663
TI  - [Study and treatment of the vascularization of the cornea].

PMID- 15433664
TI  - [Technic of free dermoepidermal eyelid grafts].

PMID- 15433665
TI  - [Two cases of retrolental fibroplasia].

PMID- 15433666
TI  - [Hyaline verrucosities of the papilla and alterations of the field of vision].

PMID- 15433667
TI  - [Acute Garcin syndrome due to a plasmocytoma at the base of the skull].

PMID- 15433668
TI  - [Radiological study of the sphenoid fissure].

PMID- 15433669
TI  - Incision and closure of the wound in cataract operations; a study of the Graefe
      knife versus the keratomescissors incision and a method of suture of the deep
      wound.

PMID- 15433670
TI  - Management of strictures of the lacrimal canaliculi with polyethylene tubes.

PMID- 15433671
TI  - Tonographic method for measuring the facility and rate of aqueous flow in human
      eyes.

PMID- 15433672
TI  - A unified concept of aqueous humor dynamics and the maintenance of intraocular
      pressure; an elaboration of the secretion-diffusion theory.

PMID- 15433673
TI  - Ocular findings in the newborn infant; a preliminary report.

PMID- 15433674
TI  - Cervical sympathectomy in nonsyphilitic interstitial keratitis with
      vestibuloauditory symptoms; report of a case.

PMID- 15433675
TI  - Retrolental fibroplasia as a syndrome pathogenesis and classifications.

PMID- 15433676
TI  - Results of operation for cataract with primary glaucoma.

PMID- 15433677
TI  - Migrainoid headaches; their ocular manifestations.

PMID- 15433678
TI  - A new instrument for lamellar keratoplasty.

PMID- 15433679
TI  - Pharmacology and toxicology; review of the literature.

PMID- 15433680
TI  - Harry Friedenwald, M.D.; 1864-1950.

PMID- 15433681
TI  - Ten year study of frontal sinusitis at the Los Angeles County General Hospital.

PMID- 15433682
TI  - Benign tumors of the esophagus; report of a case of neurofibroma.

PMID- 15433683
TI  - Diseases of the ear in relation to diseases of other organs.

PMID- 15433684
TI  - Treatment of empyema of the sella turcica of sphenoid origin.

PMID- 15433685
TI  - Primary carcinoma of the trachea.

PMID- 15433686
TI  - Psychosomatic aspects of surgical treatment of otosclerosis.

PMID- 15433687
TI  - Unusual nasal tumors; report of 2 cases.

PMID- 15433689
TI  - Etiology of otomycosis; bacterial flora of the ear.

PMID- 15433688
TI  - Etiology of otomycosis; mycologic flora of the ear.

PMID- 15433690
TI  - Peroral endoscopy.

PMID- 15433691
TI  - Etiology of otomycosis; observations on attempts to induce otomycosis in rabbits.

PMID- 15433692
TI  - Etiology of otomycosis; clinical observations.

PMID- 15433693
TI  - Double malignant tumor associated with pulmonary tuberculosis and
      esophagobronchial fistula.

PMID- 15433694
TI  - Tumors of the face.

PMID- 15433695
TI  - Streptomycin in treatment of scleroma; report of 3 cases with successful results.

PMID- 15433696
TI  - Fractures of the facial bones.

PMID- 15433697
TI  - Primary lymphangioendothelioma of the nose.

PMID- 15433698
TI  - Attempted fenestration operation in a case of absence of lumen of semicircular
      canals.

PMID- 15433699
TI  - The testis. I. The normal testis.

PMID- 15433700
TI  - The testis. II. Abnormalities of spermatogenesis; atresia of the excretory ducts.

PMID- 15433701
TI  - Sclerosing lipogranuloma.

PMID- 15433702
TI  - Accuracy of sampling by needle biopsy in diffuse liver disease.

PMID- 15433703
TI  - Localization of myocardial infarcts with respect to the muscle bundles of the
      heart.

PMID- 15433704
TI  - Pancreatic lesions associated with chronic ulcerative colitis.

PMID- 15433705
TI  - Effect of adenine on rats.

PMID- 15433706
TI  - Primary cardiovascular amyloidosis; its clinical manifestations, pathology and
      histogenesis.

PMID- 15433707
TI  - Effects of vitamin E deficiency and cod liver oil on myopathy in mice.

PMID- 15433708
TI  - Deaths in hospitalized eczema infants.

PMID- 15433709
TI  - Chickenpox simulating Kaposi's varicelliform eruption; report of 2 cases.

PMID- 15433710
TI  - Recent trends in pediatric anesthesia.

PMID- 15433712
TI  - The etiology of rachitis.

PMID- 15433711
TI  - Preventive psychiatry in pediatrics.

PMID- 15433713
TI  - CLINICAL-pathological conference; prodromal measles; interstitial pneumonia.

PMID- 15433714
TI  - The influence of microwave diathermy on the swelling and trismus resulting from
      odontectomy.

PMID- 15433715
TI  - Sterilization of water in hydrotherapeutic tank by underwater use of ultraviolet
      rays.

PMID- 15433716
TI  - Clinical electromyography; physiologic basis, instrumentation, diagnostic value.

PMID- 15433717
TI  - The prevention of ultraviolet erythema by topical application of pyribenzamine.

PMID- 15433718
TI  - Transfer of respirator patients.

PMID- 15433719
TI  - Educational therapy in the rehabilitation of the tuberculous.

PMID- 15433720
TI  - Ambulation of patients with spastic hemiplegia; further observations.

PMID- 15433721
TI  - Sludged blood following severe thermal burns.

PMID- 15433722
TI  - Postoperative alterations in the coagulation mechanism of the blood; observations
      on circulating thromboplastin.

PMID- 15433723
TI  - Prostatic cancer; further investigation of hormonal relationships.

PMID- 15433724
TI  - Carcinoma of the prostate gland; results of conservation management.

PMID- 15433725
TI  - Anatomic study of the portal vein and its main branches.

PMID- 15433726
TI  - Reconstruction of the bile ducts with an isolated segment of jejunum; an
      experimental study.

PMID- 15433727
TI  - Comminuted fractures of the os calcis; choice of treatment.

PMID- 15433728
TI  - Treatment of mixed tumors of the parotid gland by subtotal parotidectomy.

PMID- 15433729
TI  - Management of bleeding peptic ulcer.

PMID- 15433730
TI  - Local and systemic effects of heat and cold in rats.

PMID- 15433731
TI  - Experiments on local hypothermia for treatment of burns and frostbite.

PMID- 15433732
TI  - Pseudocysts of the pancreas; total excision; report of a case.

PMID- 15433733
TI  - Treatment of post-thrombotic syndrome by interruption of superficial femoral
      vein.

PMID- 15433734
TI  - Allergic reactions following the intravenous injection of corn sugar (dextrose).

PMID- 15433735
TI  - Adhesions resulting from removal of serosa from an area of bowel; failure of
      "oversewing" to lower incidence in the rat and the guinea pig.

PMID- 15433736
TI  - Excretory urography versus retrograde urography; a ureteral compression technic.

PMID- 15433737
TI  - Present day methods of disinfecting the skin; survey of disinfectants and
      technics currently employed in the hospitals of the United States and Canada.

PMID- 15433738
TI  - New simplified technic for localization of foreign body.

PMID- 15433739
TI  - [Blue neuro-nevi].

PMID- 15433740
TI  - [Biological aspects of experimental arteriopathy].

PMID- 15433741
TI  - [Frequency and entity of aortic atherosclerosis in chronic and acute
      endocarditis; inflammatory genesis of the atherosclerotic process].

PMID- 15433742
TI  - [The question of relations between atherosclerosis and tubercular toxicosis].

PMID- 15433743
TI  - [Research on the profile and limits of fibrinoid metamorphosis; fibrinoid
      degeneration of E. Neumann].

PMID- 15433744
TI  - [Endothelium and reticuloendothelium in pathological hemopoiesis. I. Framework
      and critical review of the bibliographic data].

PMID- 15433745
TI  - [Possibility of hemoblastic evolution of the vascular endothelium. II.
      Experimental results, interpretative deductions and conclusions].

PMID- 15433746
TI  - [Anatomopathological study of spontaneous and traumatic rupture of the spleen].

PMID- 15433747
TI  - [Histopathological picture following intravenous inoculation into the guinea pig
      of tubercle bacilli living and attenuated (BCG) or killed (Petragnani's integral
      anatuberculin)].

PMID- 15433748
TI  - [The so-called Baber and Hurthle cell tumors of the thyroid].

PMID- 15433749
TI  - [Influence of parabiosis (double and triple) on the survival of animals
      previously nephrectomized and uremic].

PMID- 15433750
TI  - [Biometric research on the various glomerular modifications and on the number of
      undamaged glomeruli in subchronic and chronic nephritis].

PMID- 15433751
TI  - [Experimental tuberculo-toxic splenitis].

PMID- 15433752
TI  - [Gastric and intestinal carcinoma in the young (0-20 years)].

PMID- 15433753
TI  - [Pathogenesis and significance of megaloblastosis in various hemopathic
      syndromes; experimental contribution to the problem of megaloblasts].

PMID- 15433754
TI  - [Modifications of the blood and of the hemopoietic organs following the
      introduction of estrogens in animals with liver lesions].

PMID- 15433755
TI  - [Anatomical aspects and pathogenesis of esophago-tracheal fistulas of malignant
      granuloma: histologic modifications of roentgen treatment of Sternberg tissue].

PMID- 15433756
TI  - [Chemical determination of 11-oxycorticoids in the urine and in the blood].

PMID- 15433757
TI  - [Research on the vaginal cytology in women with liver disease in menopause].

PMID- 15433758
TI  - [Relation between vitamins and thymus. III. Action of lactoflavin, nicotinamide,
      pyridoxine and pantothenic acid].

PMID- 15433759
TI  - [Vitamin interrelations. I. Influence of vitamin B complex on the tissue content
      of vitamin C].

PMID- 15433760
TI  - [Correlations between uric acid metabolism and ketone bodies metabolism. IV.
      Behavior of uricemia and uricosuria after administration of beta-hydroxybutyric
      acid in patients with liver disease].

PMID- 15433761
TI  - [Vitamins and the process of acylation of p-aminosalicylic acid; action of
      thiamine and nicotinamide on the acetylation of PAS].

PMID- 15433762
TI  - [Relation of tuberculosis allergy with streptomycin therapy and with
      antituberculosis vaccination; case of meningitis in BCG vaccinated].

PMID- 15433763
TI  - [Short wave therapy of bronchial asthma].

PMID- 15433764
TI  - [Radiologic observations on anaphylaxis; anaphylaxis of the digestive system. II.
      Duodenum, jejunum, ileum].

PMID- 15433765
TI  - [Therapy of ocular hypertensive syndromes in relation to the physiopathology of
      the circulation].

PMID- 15433766
TI  - [Gastric kinesis and exocrine and endocrine secretion of the pancreas; clinico
      experimental observations by means of the simultaneous use of gastrographic and
      duodenal tubes].

PMID- 15433767
TI  - [Metabolism and glucide regulation in the pathology of gastric resection].

PMID- 15433768
TI  - [Filtrating cholecystitis].

PMID- 15433769
TI  - [Research on metabolism in total gastrectomy. II. Research on the absorption of
      ascorbic acid, aneurin, and nicotinamide].

PMID- 15433770
TI  - [Endoscopic aspects of the esophagus in a case of acanthosis nigricans].

PMID- 15433771
TI  - [Therapeutic problem of osteomyelitis of the cranial bones in relation to
      antibiotic therapy].

PMID- 15433772
TI  - [A peculiar neuromuscular mechanism of the muscle of the malleus; research on
      guinea pigs].

PMID- 15433773
TI  - [Leukoplakia of the oral cavity and precancerous conditions].

PMID- 15433774
TI  - [Tumors of cylindromatous evolution of the head and neck].

PMID- 15433775
TI  - [Surgery of the middle ear and of the vestibular labyrinth by the transmeatic
      route].

PMID- 15433776
TI  - [Experimental avitaminosis A and the ear].

PMID- 15433777
TI  - [Experimental research on nerve anastomosis in the treatment of recurrent
      laryngeal paralysis].

PMID- 15433778
TI  - [Medical treatment of Meniere's syndrome].

PMID- 15433779
TI  - [Present state of anesthesia in otorhinolaryngologic surgery].

PMID- 15433780
TI  - [Rational use of pre-anesthesia in otorhinolaryngology].

PMID- 15433781
TI  - [Endotracheal anesthesia in otorhinolaryngologic surgery].

PMID- 15433782
TI  - [Trichloroethylene as an analgesic in otorhinolaryngology].

PMID- 15433783
TI  - [Anesthesia for the fenestration operation].

PMID- 15433784
TI  - [Anesthesia with protoxide of nitrous oxide and trichloroethylene in ear
      surgery].

PMID- 15433785
TI  - [Choice of anesthesia in laryngo-tracheo-bronchea and esophageal endoscopic
      interventions].

PMID- 15433786
TI  - [Diverse activity of local anesthesia on the vibratile cilia according to the
      reaction of the surrounding media].

PMID- 15433787
TI  - [Electrocardiographic modifications during esophagoscopy without anesthesia, with
      local, and with general anesthesia].

PMID- 15433788
TI  - [Effect on the circulatory system of trichloroethylene].

PMID- 15433789
TI  - [Electrocardiogram, oscillogram, pneumogram in anesthesia with
      trichloroethylene].

PMID- 15433790
TI  - [Lysozymic activity of saliva and of nasal secretions in relation to superficial
      anesthesia; experimental research in vivo and in vitro].

PMID- 15433791
TI  - [Variations in the technic of analgesia with trichloroethylene in surgery of the
      tonsils].

PMID- 15433792
TI  - [Laryngeal surface anesthesia by the nasal route; note on operatory technic].

PMID- 15433793
TI  - [Action of pentothal on respiration studied through the alterations caused by
      this substance on the sensitivity of the chemoreceptors in the carotid sinus
      area].

PMID- 15433794
TI  - [Electrocardiographic investigation during tracheobronchoscopy under local
      anesthesia].

PMID- 15433795
TI  - [Sun and sea cure in arthrosis and non-tuberculous chronic arthritis].

PMID- 15433796
TI  - [Sun and sea cure in arthrosis and non-tuberculous chronic arthritis].

PMID- 15433797
TI  - [An institution for sun and sea cure].

PMID- 15433798
TI  - [Arthrotomy in the diagnosis of chronic arthrosynovitis of the knee].

PMID- 15433799
TI  - [Arthroplasty of the hip with interposition of a vitallium cup; indications and
      operative technic].

PMID- 15433800
TI  - [Case of vertebral echinococcosis; differential diagnosis of disk hernia].

PMID- 15433801
TI  - [Case of kyphoscoliosis complicated by paraplegia].

PMID- 15433803
TI  - [Diagnosis of the osteoarticular localizations of undulant fever].

PMID- 15433802
TI  - [Results of meniscectomy, with special reference to arthritis deformans].

PMID- 15433804
TI  - [The Genna constant and its relation to the pathogenesis of arthritis deformans
      of the knee following static alterations of the lower extremity].

PMID- 15433805
TI  - [Antibiotics in osteoarthritic tuberculosis].

PMID- 15433806
TI  - [Delayed results in 50 cases of reduction-arthrodesis in inveterate unilateral
      congenital dislocation of the hip].

PMID- 15433807
TI  - [Ultrasonic therapy in arthrosis].

PMID- 15433808
TI  - [Cadmium reaction in the prognosis of osteoarthritic tuberculosis].

PMID- 15433809
TI  - [Rare congenital malformation of the scapula].

PMID- 15433810
TI  - [Etiopathogenetic correlations in some osteochondrodystrophies; clinico
      statistical findings].

PMID- 15433811
TI  - [Toxic phagedenic ulcer of the thigh due to osteosynthesis with bands of nickel
      plated brass].

PMID- 15433812
TI  - [Recklinghausen's osteodystrophia fibrosa cystical].

PMID- 15433813
TI  - [50 Fractures of the patella].

PMID- 15433814
TI  - [Surgical treatment of scoliosis].

PMID- 15433815
TI  - [Radiographic picture of hemophilic arthropathy].

PMID- 15433816
TI  - [Correlation between rachischisis and juvenile dystrophy of the bones of the
      foot].

PMID- 15433817
TI  - [The Mauriac syndrome: pre-puberal diabetes with hepatomegaly and
      underdevelopment].

PMID- 15433818
TI  - [Modifications of the muscularis mucosae in chronic gastritis; pathogenesis and
      morphological significance].

PMID- 15433819
TI  - [Pallesthesia in diabetics].

PMID- 15433820
TI  - [Importance of the spleen in experimental hemolytic anemia produced by
      immunohemolysin].

PMID- 15433821
TI  - [Gastrohematic balance of sodium, potassium and chlorine; index of chlorine
      sodium utilization].

PMID- 15433822
TI  - [Action of histamine and antihistamines on the propulsive motility of the
      intestine].

PMID- 15433823
TI  - [Culture filtrate of Penicillium notatum as a solvent of crystallized penicillin;
      action of the filtrate on repair of experimental wounds].

PMID- 15433824
TI  - [The problems of social insurance].

PMID- 15433825
TI  - [Brief indications for the problems of schermographic technic].

PMID- 15433826
TI  - [Atypical tuberculosis, a problem of major importance].

PMID- 15433827
TI  - [Current technic of Monaldi's endocavitary aspiration].

PMID- 15433828
TI  - [The value of stratigraphic research in the sanatorium].

PMID- 15433829
TI  - [The real and practical value of the inhibition of streptomycin by certain
      pathological substances].

PMID- 15433830
TI  - [Permeability to p-aminosalicylic acid of the meningoencephalic barrier in
      children].

PMID- 15433831
TI  - [Hematic concentration and urinary elimination of PAS during continuous
      treatment].

PMID- 15433832
TI  - [Incomplete Karthagener's syndrome].

PMID- 15433833
TI  - [Thrombocytopenia and hemorrhagiparous syndromes].

PMID- 15433834
TI  - [High femoral osteotomy with internal fixation].

PMID- 15433835
TI  - [Antibiotics and blood coagulation in the puerperium].

PMID- 15433836
TI  - [Research in cardiology in the Hospital Lariboisiere, Paris].

PMID- 15433837
TI  - [Intestinal occlusion due to Meckel's diverticulum; case report].

PMID- 15433838
TI  - [Calcified chronic pancreatitis; report of a case with fatty liver].

PMID- 15433839
TI  - [A case of nodular hepatomegaly].

PMID- 15433840
TI  - [Clinico-pathological session: pulmonary arteritis (endarteritis) of undetermined
      type].

PMID- 15433841
TI  - [Clinical experiments with ACTH and cortisone].

PMID- 15433842
TI  - [Variations in the coronary distribution in man and its relation to vascular
      pathology of the heart; analysis of 17 cases by radiography and dissection].

PMID- 15433843
TI  - [Analgesia in obstetrics; saddle block].

PMID- 15433844
TI  - [Amputation of the thigh; the Holden tendoplastic method].

PMID- 15433845
TI  - [2 Cases of insulin resistance].

PMID- 15433846
TI  - [Sarcoma of the penis].

PMID- 15433848
TI  - [Clinico-pathological session; chronic and acute ulcerated duodenitis; chronic
      fibrous pancreatitis with acute foci].

PMID- 15433847
TI  - [Massive resection of the small intestine; case report].

PMID- 15433849
TI  - [Genital prolapse; therapeutic problem].

PMID- 15433850
TI  - [Blood chemistry and its practical applications in clinical medicine].

PMID- 15433852
TI  - [Current concepts of poliomyelitis].

PMID- 15433851
TI  - [Present value of biological pregnancy tests in the primigravida].

PMID- 15433853
TI  - [Necrotic purpura].

PMID- 15433854
TI  - [Scarlet fever and penicillin therapy].

PMID- 15433855
TI  - [Calcinosis universalis; a personal observation].

PMID- 15433856
TI  - [Neuropsychiatric sequels of purulent meningitis; study of children of first
      infancy using the developmental standards of Gesell].

PMID- 15433858
TI  - [Congenital heart diseases].

PMID- 15433857
TI  - [The premature infant; alimentation of the premature infant].

PMID- 15433859
TI  - [Vaccination with B.C.G. in America].

PMID- 15433860
TI  - [Acute craniocerebral injuries; prognosis; causes of death; therapy;
      physiopathology of cranial hypertension].

PMID- 15433861
TI  - [A rare and complex case of alterations in cardiac rhythm].

PMID- 15433862
TI  - [Spontaneous rhinorrhea; a case treated surgically].

PMID- 15433863
TI  - [Vertebral echinococcosis; total resection of the fifth lumbar vertebra].

PMID- 15433864
TI  - [Anesthesia of the phrenic nerve by abdominal route].

PMID- 15433865
TI  - The surgeon, the pathologist and metastases.

PMID- 15433866
TI  - The significance of experimental cancer research.

PMID- 15433867
TI  - [Radiotherapy of malignant tumors].

PMID- 15433868
TI  - The relationship between hormones and malignant tumours.

PMID- 15433870
TI  - Arthroplasty in stiff elbow-joints.

PMID- 15433869
TI  - Experiences in vagotomy.

PMID- 15433872
TI  - Spontaneous rupture of the spleen in malaria.

PMID- 15433871
TI  - Cleft palate, with special reference to the muscle suture and the posterior
      fistula.

PMID- 15433873
TI  - Congenital anteversion of the neck of the femur.

PMID- 15433874
TI  - Diabetic coma.

PMID- 15433875
TI  - The use of continuous caudal or spinal anesthesia in the treatment of eclampsia.

PMID- 15433876
TI  - An introduction to dianetics.

PMID- 15433877
TI  - [I. P. Pavlov and present day problems of contemporary pathological physiology].

PMID- 15433878
TI  - [Tissular blastomogenic substances in leukosis].

PMID- 15433879
TI  - [Pathological anatomy of experimental leukosis, induced by injection of benzol
      extracts from organs of patients who died of leukosis].

PMID- 15433880
TI  - [Experimental morphological study of leukosis in mice].

PMID- 15433881
TI  - [Behavior of normal and malignant cells in vital staining].

PMID- 15433882
TI  - [Development of cysts from implants of Muller's epithelium (tubular and
      uterine)].

PMID- 15433883
TI  - [Modifications experimentally induced by repeated pregnancy without lactation in
      mammary glands of noncancerous strain of mice].

PMID- 15433884
TI  - [Content of water soluble adenosintriphosphatase in experimental sarcoma in
      different stages of development].

PMID- 15433885
TI  - [Culture of murine cancer in the vitelline sac of the chick embryo].

PMID- 15433886
TI  - [Antigenic characteristics of heterogenic tumors in culture on the allantoic
      membrane of the chick embryo].

PMID- 15433887
TI  - [Effect of spreading factor on the basic argyrophil substance].

PMID- 15433888
TI  - [Carcinosis of pulmonary lymph vessels].

PMID- 15433889
TI  - [Recent research in venous valves and criticism of Bardeleben's theory].

PMID- 15433890
TI  - [Total evisceration according to G. V. Shor in autopsies].

PMID- 15433891
TI  - [Use of sulfur compounds in replacement of gold chloride after silver
      impregnation of the nervous system].

PMID- 15433892
TI  - [In memory of N. V. Uskov].

PMID- 15433893
TI  - [I. P. Pavlov's theory of the constitution].

PMID- 15433894
TI  - [Role of different sections of the central nervous system in the pathogenesis of
      anaphylactic shock].

PMID- 15433895
TI  - [Adrenalin-secretory reflexes from the carotid sinus of dogs in bacterial
      allergy].

PMID- 15433896
TI  - [Effect of curare on allergic reactions of the chemoreceptors of the carotid
      sinus].

PMID- 15433897
TI  - [Reflex stimulation of the nervous system in diuretic disorders].

PMID- 15433898
TI  - [Role of various kinds of glia in the process of metabolism of lipoid products of
      disintegration].

PMID- 15433899
TI  - [Pathologico-anatomical modifications of the central nervous system in malignant
      hypertension].

PMID- 15433900
TI  - [Pathomorphology of gustatory innervation of the tongue in tuberculosis of the
      respiratory tract].

PMID- 15433901
TI  - [Pathological anatomy of tuberculous meningitis treated with streptomycin].

PMID- 15433902
TI  - [Functional modification of the nervous system in protein deficiency].

PMID- 15433903
TI  - [Certain autonomic reactions in mechanical stimulation of the dural membrane of
      the spinal cord].

PMID- 15433904
TI  - [Rare case of osteo-dysplasia].

PMID- 15433905
TI  - [Morphology of congenital cerebral hernia].

PMID- 15433906
TI  - [Barre-Manson's tumors].

PMID- 15433907
TI  - [Aleksei Sergeevich Shkliarevskii, 110 years since his birth].

PMID- 15433908
TI  - [Gastroduodenal ulcers; clinical study and etiopathogenesis of 207 cases].

PMID- 15433909
TI  - [Clinico-pathological sessions; hypertrophy and dilatation of the heart; arterial
      nephrosclerosis; intercapillary glomerulosclerosis].

PMID- 15433910
TI  - [Cirrhosis of the liver].

PMID- 15433911
TI  - [Clinico-pathological sessions; cirrhosis of the liver, portal type; atrophy of
      the testes].

PMID- 15433912
TI  - [Modifications of the retina in amotio retinae].

PMID- 15433913
TI  - [Absence of blastomatogenous action of nitrogen compounds on epithelium of the
      skin].

PMID- 15433914
TI  - [Acrorigosis and symmetrical eczema of the breast, in relation to chlorosis].

PMID- 15433915
TI  - [Action of vitamin B12 against pernicious anemia].

PMID- 15433916
TI  - [The sex problem in prisons].

PMID- 15433917
TI  - [Variations of serum electrolytes in relation to sodium pentothal narcosis].

PMID- 15433918
TI  - [Conclusions regarding Paracelsus].

PMID- 15433919
TI  - The nature of bone.

PMID- 15433920
TI  - Appearances can be deceptive.

PMID- 15433921
TI  - The personal touch.

PMID- 15433922
TI  - Gold inlay technique.

PMID- 15433923
TI  - Fees.

PMID- 15433924
TI  - Dens in dente.

PMID- 15433925
TI  - A plan for dental practice.

PMID- 15433926
TI  - [The contagionists are pleased].

PMID- 15433927
TI  - [Gold therapy by rectal route; its advantages, notably in the treatment of
      asthma].

PMID- 15433928
TI  - [Attempted cryogenine-sulfamidotherapy of febrile tuberculosis].

PMID- 15433929
TI  - [The biological process of cancerization].

PMID- 15433930
TI  - [Hypothesis on the parasito-colibacillary etiology of certain epitheliomas of the
      human digestive tract and on the different pathogenic mechanisms possible].

PMID- 15433931
TI  - [Tuberculous, caseous basal pleurisy].

PMID- 15433932
TI  - [Effect of streptomycin on tuberculous meningitis and miliary tuberculosis of the
      lungs].

PMID- 15433933
TI  - [Psychodiagnosis of pulmonary tuberculous with the Rorschach test].

PMID- 15433934
TI  - [Clinical significance of contraction atelectasis in the general aspect of
      pulmonary tuberculosis].

PMID- 15433935
TI  - [Theoretic and practical significance of the tuberculin stimulus threshold].

PMID- 15433936
TI  - [Miliary tuberculosis with clinical aspect of panmyelopathy, and its relation to
      Landouzy's typhobacillosis].

PMID- 15433937
TI  - [Preliminary results in TB I therapy of osteoarticular tuberculosis].

PMID- 15433938
TI  - [Pregnancy and tuberculosis].

PMID- 15433939
TI  - [Methods and aims of occupational therapy for the tuberculous].

PMID- 15433940
TI  - [In memoriam Gustav Baer].

PMID- 15433941
TI  - [Autonomic nervous system and lung].

PMID- 15433942
TI  - [Physiology of pneumoperitoneum].

PMID- 15433943
TI  - [Pulmonary tuberculosis in a central German city at the end of 1948].

PMID- 15433944
TI  - [Resistance of the tubercle bacillus to streptomycin and to streptomycin in
      combination with TB I in tuberculous meningitis].

PMID- 15433945
TI  - [Globular exudate].

PMID- 15433946
TI  - [Statistics on tuberculosis, based on autopsies in Gottingen].

PMID- 15433947
TI  - [Some old remedies in present light].

PMID- 15433948
TI  - [Hurler-Pfaundler disease].

PMID- 15433949
TI  - [Paralytic dementia and its treatment].

PMID- 15433950
TI  - [Clinical and functional study of acute hepatitis and its sequels].

PMID- 15433951
TI  - [Therapy in liver disease].

PMID- 15433952
TI  - [The liver and chronic alcoholism].

PMID- 15433953
TI  - [New aspects in prognosis and treatment of acute infectious hepatitis].

PMID- 15433954
TI  - [Mechanism, value and utility of the usual liver function tests].

PMID- 15433955
TI  - [Porta-caval shunt in esophageal hemorrhage].

PMID- 15433956
TI  - [Experimental glomerulonephritis, and the etiology of glomerulonephritis in man].

PMID- 15433957
TI  - [Second European Congress for Gastroenterology, Madrid, 3-7 May 1950].

PMID- 15433958
TI  - [Examination of the bile in non-calculous inflammations of the gallbladder and
      biliary tract].

PMID- 15433959
TI  - [Pharmacology of the biliary tract].

PMID- 15433960
TI  - [Biochemical modifications of the plasma in diseases of the biliary tract].

PMID- 15433961
TI  - [Biliary dyskinesia; clinical, physiopathological and radiomanometric study].

PMID- 15433962
TI  - [The etiology of cholecystitis].

PMID- 15433963
TI  - [Clinical aspects of non-calculous cholecystitis].

PMID- 15433964
TI  - [Role of the biliary tract in catarrhal jaundice].

PMID- 15433965
TI  - [Congenital abnormalities of the biliary tract].

PMID- 15433966
TI  - [Internal therapy of non-calculous chronic cholecystitis].

PMID- 15433967
TI  - [Acquired benign strictures of the bile ducts (excepting calculi)].

PMID- 15433968
TI  - [Anesthetization of the horse with narkovet].

PMID- 15433969
TI  - [Multiple hemorrhage of the liver in bovine tuberculosis (peliosis hepatis)].

PMID- 15433970
TI  - [Coitus diseases and attempts at control in rural practice].

PMID- 15433971
TI  - [Natural ectromelia infection in white mice].

PMID- 15433972
TI  - [Experiences in extraction of foreign bodies].

PMID- 15433973
TI  - [Igelit poisoning in a goat].

PMID- 15433974
TI  - Electron microscopy of developing plant cell walls.

PMID- 15433975
TI  - Electron microscopical observations on bacterial cytology; a study on
      flagellation.

PMID- 15433976
TI  - Contribution to the chemistry of leucaemic urine.

PMID- 15433977
TI  - A preliminary note on the actomyosin from uterus studied in ultracentrifuge.

PMID- 15433978
TI  - On the actomyosin as a protein complex.

PMID- 15433979
TI  - Citric acid synthesis by the condensation of acetate and oxalacetate in rabbit
      kidney.

PMID- 15433980
TI  - On the mechanism of synthesis of acetyl choline; the synthesis of citrate by
      brain enzymes.

PMID- 15433981
TI  - Synthesis of protein and other cell substances from acetic acid in isolated bone
      marrow.

PMID- 15433982
TI  - [Chromatographic separation of amino acids and peptides; the individual amino
      acids of insulin with a note on the determination of proline].

PMID- 15433983
TI  - The essential groups of insulin.

PMID- 15433984
TI  - Inactivation of crotoxin by group-specific reagents.

PMID- 15433985
TI  - Cyanate-methaemoglobin.

PMID- 15433986
TI  - [Some new observations on the mode of attack of horse globin and egg albumin by
      pepsin].

PMID- 15433987
TI  - Studies of citric acid metabolism in heart muscle.

PMID- 15433988
TI  - [The effect of 3-methyl indole on carbohydrates].

PMID- 15433989
TI  - Measurement of pellet volume in the analytical ultracentrifuge.

PMID- 15433990
TI  - A technique for the cultivation and preparation of tissue cultures for electron
      microscopy.

PMID- 15433991
TI  - The fine structure of connective tissue fibrils.

PMID- 15433992
TI  - Emission spectra of luminous bacteria.

PMID- 15433993
TI  - On the relation between the formation of assimilatory pigments and the rate of
      photosynthesis in etiolated oat seedlings.

PMID- 15433994
TI  - On the role of the carotenoids in photosynthesis in Rhodospirillum rubrum.

PMID- 15433995
TI  - [On the chemical constitution of an antigenic lipo-polysaccharide extract of
      Mycobacterium tuberculosis var. hominis].

PMID- 15433996
TI  - Chromatographic investigations of amino acids from micro-organisms. II. Isolation
      of two unknown substances from Corynebacterium diphtheriae.

PMID- 15433997
TI  - The detection of Jaffe-positive substance in blood serum by paper partition
      chromatography; the problem of apparent creatinine.

PMID- 15433998
TI  - [Some peptides resulting from the incomplete hydrolysis of lysozyme].

PMID- 15433999
TI  - [Contribution to the study of the fermentation and respiration of Escherichia
      coli. I. Action of certain inhibitors on the respiration and fermentation of
      Escherichia coli].

PMID- 15434000
TI  - [Contribution to the study of the fermentation and respiration of Escherichia
      coli. II. Action of some inhibitors on the dehydrogenases and the phosphatases of
      Escherichia coli].

PMID- 15434001
TI  - Inactivation of thromboplastin by cobra venom.

PMID- 15434002
TI  - [Specificity of alkaline phosphatases of animal organs and alkaline phosphatase
      of human serum in hyperphosphatasemias].

PMID- 15434003
TI  - The tryptic inhibitor and the availability of cystine and methionine in raw and
      germinated soya beans.

PMID- 15434004
TI  - [C-mitotic activity of the gamma-isomer and of the delta-hexachlorocyclohexane,
      with reference to the influence of mesoinositol and sodium inositophosphate].

PMID- 15434005
TI  - The distribution of aneurinpyrophosphate between the nucleus and the cytoplasm of
      chicken erythrocytes.

PMID- 15434006
TI  - Hereditary spherocytic anemia in the Negro.

PMID- 15434007
TI  - Severe Mediterranean anemia (Cooley's anemia) in a Chinese child.

PMID- 15434008
TI  - The effect of racial mixtures upon erythrocytic sickling.

PMID- 15434009
TI  - Familial nonspherocytic hemolytic anemia.

PMID- 15434010
TI  - Paroxysmal nocturnal hemoglobinuria; the mechanism of hemolysis and its relation
      to the coagulation mechanism.

PMID- 15434011
TI  - Paroxysmal nocturnal hemoglobinuria; a specific test for the disease based on the
      ability of thrombin to activate the hemolytic factor.

PMID- 15434012
TI  - Microscopic and histochemical studies on the Auer bodies in leukemic cells.

PMID- 15434013
TI  - Beta-Glucuronidase of human white blood cells.

PMID- 15434014
TI  - The efficiency of an iron-molybdenum preparation as evaluated by means of iron
      absorption tests.

PMID- 15434015
TI  - The cause of the sexual differences in erythrocyte hemoglobin and serum iron
      levels in human adults.

PMID- 15434016
TI  - "Idiopathic" hypochromic anemia; an obituary.

PMID- 15434017
TI  - [New remedies for tuberculosis].

PMID- 15434018
TI  - Esophageal diverticulum.

PMID- 15434019
TI  - Alterations in body potassium: clinical implications; review of the literature.

PMID- 15434020
TI  - Rectal biopsy as a criterion for evaluation of treatment in schistosomiasis
      mansoni.

PMID- 15434021
TI  - [Common children's diseases in Puerto Rico].

PMID- 15434022
TI  - [Oral hygiene in our children].

PMID- 15434023
TI  - [Calculi in the human organism].

PMID- 15434025
TI  - [In Memoriam Dr. Emilio Martinez (1864-1948)].

PMID- 15434024
TI  - [Latest advances in ophthalmology].

PMID- 15434026
TI  - [Isotopes and atomic energy in medicine and cancer].

PMID- 15434027
TI  - [Cholesteatoma of the attic of traumatic origin].

PMID- 15434028
TI  - [Embryonic tumor of the mediastinum].

PMID- 15434029
TI  - [Indications for radical resection of cervical lymph nodes in metastatic cancer].

PMID- 15434030
TI  - [Malignant tumors of the thyroid].

PMID- 15434031
TI  - [Hemangiomas; classification, diagnosis and treatment].

PMID- 15434032
TI  - [Tumors of the nasopharynx].

PMID- 15434033
TI  - [Transvaginal roentgenotherapy in the treatment of cancer of the cervix].

PMID- 15434034
TI  - [New serum for the treatment of cancer].

PMID- 15434035
TI  - [Diagnosis of cancer of the lung by cytologic examination of sputum].

PMID- 15434036
TI  - [Modern advances in hematology; in the diagnosis of malignancy by cellular
      exfoliation, and in public health of interest in cancerology].

PMID- 15434037
TI  - [Chloromycetin in typhoid fever].

PMID- 15434038
TI  - [Crystallized procaine penicillin G].

PMID- 15434039
TI  - [Psychological development of the child; information essential for the
      pediatrician].

PMID- 15434040
TI  - [Cardiospasm].

PMID- 15434041
TI  - [Clinico-pathological sessions; fibrocystic disease of the pancreas].

PMID- 15434042
TI  - [Clinico-pathological sessions; malignant lymphoma].

PMID- 15434043
TI  - [Clinico-pathological sessions; intestinal infarct].

PMID- 15434044
TI  - [Clinico-pathological sessions; tuberculous meningoencephalitis].

PMID- 15434045
TI  - [Clinico-pathological sessions; astrocytoma of the cerebellum].

PMID- 15434046
TI  - [Clinico-pathological sessions; hemolytic disease due to the Rh factor].

PMID- 15434047
TI  - [Preoperative treatment and anesthesia in hyperthyroidism].

PMID- 15434048
TI  - [Functional result of small lumens in gastrojejunal anastomosis for subtotal
      gastrectomy in gastroduodenal ulcer].

PMID- 15434049
TI  - [Brunschwig operation].

PMID- 15434050
TI  - [Secondary hepatic and peritoneal hydatidosis].

PMID- 15434051
TI  - [Hyperthyroidism; operation with brief preoperative treatment].

PMID- 15434052
TI  - [Ulcer of the lesser curvature; fulminating hematemesis].

PMID- 15434053
TI  - [Ulcer of the lesser curvature; fulminating hematemesis].

PMID- 15434054
TI  - [Preoperative treatment and anesthesia in hyperthyroidism].

PMID- 15434055
TI  - [Large inguinal hernia with prolapse of the iliopelvic colon; conduct of
      treatment].

PMID- 15434056
TI  - [Cancer of the lower lip].

PMID- 15434057
TI  - [Gastrectomy and mesenteric infarct].

PMID- 15434058
TI  - [Preoperative treatment and anesthesia in hyperthyroidism].

PMID- 15434060
TI  - [Shock].

PMID- 15434059
TI  - [Gastrectomy and mesenteric infarct].

PMID- 15434061
TI  - [Importance of pharmacocholangiography in the operative study of the common bile
      duct].

PMID- 15434062
TI  - [Cancer of the lower lip].

PMID- 15434063
TI  - [Epithelioma of the tear ducts].

PMID- 15434064
TI  - [Myxoglobulosis of the appendix].

PMID- 15434065
TI  - [Pulmonary hydatidosis; surgical therapy].

PMID- 15434066
TI  - [Gastrectomy and mesenteric infarct].

PMID- 15434067
TI  - [Cancer of the lower lip].

PMID- 15434068
TI  - [Pulmonary hydatidosis; surgical therapy].

PMID- 15434069
TI  - [Chaklin operation in spondylolisthesis and in listhetic scoliosis].

PMID- 15434070
TI  - [Functional disorder of Oddi's sphincter; its importance and consequences].

PMID- 15434071
TI  - [Action of general anesthesia with pentothal induction and several details of
      technic in hyperthyroidism].

PMID- 15434073
TI  - [Functional disorder of Oddi's sphincter].

PMID- 15434072
TI  - [Pulmonary echinococcosis; surgical treatment].

PMID- 15434074
TI  - [Large inguinal hernia with slipping of the iliopelvic colon].

PMID- 15434075
TI  - [Pulmonary echinococcosis; surgical treatment].

PMID- 15434076
TI  - [Biliary dyskinesia following cholecystectomy, with a pathological cystic stump].

PMID- 15434077
TI  - [Treatment of recurrent dislocation of the shoulder by the Gallie-Lemesurier
      technic].

PMID- 15434078
TI  - [Brunschwig's operation].

PMID- 15434079
TI  - [Congenital malformation of the common bile duct].

PMID- 15434080
TI  - [Postcholecystectomy biliary dyskinesia, with pathological cystic stump].

PMID- 15434081
TI  - [Cancer of the lower lip].

PMID- 15434082
TI  - [Pulmonary echinococcosis; surgical therapy].

PMID- 15434083
TI  - [Eventration of the diaphragm].

PMID- 15434084
TI  - [Chronic osteomyelitis of the humerus; minimal trepanation and intramedullary
      penicillin; cure].

PMID- 15434085
TI  - [Massive hemorrhage due to duodenal ulcer].

PMID- 15434087
TI  - [Ulcer of the lesser curvature; fulminating hematemesis].

PMID- 15434086
TI  - [Delayed result of a parathyroid graft].

PMID- 15434088
TI  - [Pulmonary echinococcosis; surgical therapy].

PMID- 15434089
TI  - [Results obtained by total skin grafts in the surgery of hernias and
      eventrations].

PMID- 15434090
TI  - [Biliodigestive anastomosis for accidental section of the common bile-duct;
      angiocholitis].

PMID- 15434091
TI  - [Total gastrectomy for cancer with esophagoduodenal anastomosis].

PMID- 15434092
TI  - [Post-cholecystectomy biliary dyskinesia with pathological cystic stump].

PMID- 15434093
TI  - [Congenital malformation of the gallbladder].

PMID- 15434094
TI  - [Results of splenectomy in splenic anemia, purpura hemorrhagica, hemolytic
      jaundice and chronic myeloid leukemia].

PMID- 15434095
TI  - [Echinococcosis of the pleura of hepatic origin].

PMID- 15434096
TI  - [Functional disturbance of Oddi's sphincter; its importance and consequences].

PMID- 15434097
TI  - [Pulmonary echinococcosis; surgical therapy].

PMID- 15434098
TI  - [Results obtained with total skin grafts in surgery of hernias and eventrations].

PMID- 15434099
TI  - [Results of splenectomy in splenic anemia, purpura haemorrhagica, hemolytic
      jaundice and leukemia].

PMID- 15434100
TI  - [Pleural echinococcosis of hepatic origin].

PMID- 15434102
TI  - [Treatment of acute pancreatitis].

PMID- 15434101
TI  - [New technic of arthrodesis of the knee].

PMID- 15434103
TI  - [Model cholangiotensiograph of Dr. Alberto de Alzaga].

PMID- 15434104
TI  - [Cancer of the stomach; total gastrectomy; late results].

PMID- 15434105
TI  - [Advanced intraoral cancer; radical surgery].

PMID- 15434106
TI  - [Sorbitol and mannitol as substitutes for glycerine].

PMID- 15434107
TI  - [Determination of the origin of opium].

PMID- 15434108
TI  - [Thioglycolic acid in cold permanent waves].

PMID- 15434109
TI  - [Magistral preparations of p-aminosalicylic acid].

PMID- 15434110
TI  - [Liquid aluminum acetate].

PMID- 15434111
TI  - [New indicator of anthraquinone derivatives].

PMID- 15434112
TI  - [New pharmacopeias].

PMID- 15434113
TI  - [Modern criteria in the administration of the pharmacy].

PMID- 15434114
TI  - [Spectrographic determination of lead in blood].

PMID- 15434115
TI  - [Artificial radioactivity and new chemical elements].

PMID- 15434116
TI  - [Magistral preparations of aureomycin].

PMID- 15434117
TI  - [Ferrous iodide syrup].

PMID- 15434118
TI  - [Modern criteria in the administration of the pharmacy].

PMID- 15434119
TI  - [Allergy test according to Tieche in the diagnosis of smallpox].

PMID- 15434120
TI  - [Diphasicity of the action of antibacterial substances on S. typhi and Staph.
      aureus Oxford].

PMID- 15434121
TI  - [Behavior of bacteriolysis of bacteriolysis of lysozyme in tears, saliva and
      nasal secretion of full-term and premature infants].

PMID- 15434123
TI  - [Mutations induced by bacterial nucleic acids].

PMID- 15434122
TI  - [Comparative study of the methods of hydrolysis of proteins for the liberation of
      18 amino acids].

PMID- 15434124
TI  - [Paradoxical phenomenon in brucellar seroagglutination].

PMID- 15434125
TI  - [Histological findings and variations of ribonucleic acid in the cytoplasm of the
      cells of some organs of guinea pigs killed by anaphylactic shock].

PMID- 15434127
TI  - [Culture of intestinal ameba].

PMID- 15434126
TI  - [Determination of lysozyme on plates inoculated with Micrococcus lysodeicticus].

PMID- 15434128
TI  - [In memory of Antonio Carini, 1872-1950].

PMID- 15434129
TI  - [Alfredo Orlandini (April 4, 1870 - Febr 6, 1950)].

PMID- 15434130
TI  - [Pharyngo-laryngeal mycosis; clinical and experimental contribution].

PMID- 15434131
TI  - [Pathergometry and tonsillectomy].

PMID- 15434132
TI  - [Absence of meso-mucin in the so-called nasal mucosal polyps].

PMID- 15434133
TI  - [Experimental research on the sensory innervation of the larynx].

PMID- 15434134
TI  - [Weight of the organs of epinephrectomized rats during fasting].

PMID- 15434135
TI  - [Anemia of ligation of the portal vein].

PMID- 15434136
TI  - [Fractionated tyrosinuria in subjects undergoing therapy; note II].

PMID- 15434137
TI  - [Certain histochemical properties of the granules of mast cells].

PMID- 15434138
TI  - [Effect of some curarizing drugs on the lesion potential and on the electric
      conductivity of skeletal muscle].

PMID- 15434139
TI  - [Effect of the human cerebrospinal fluid on the activity of the cholinesterase].

PMID- 15434140
TI  - [Activity of the so-called specific cholinesterase of the blood following
      subarachnoid introduction of air].

PMID- 15434141
TI  - [Inhibitory power of tissues with high metabolic potential; note I].

PMID- 15434142
TI  - [Inhibitory power of tissues with high metabolic potential; note II].

PMID- 15434143
TI  - [Research on the contractile activity of intestinal smooth muscles; potentiation
      of the action of acetylcholine by 933F].

PMID- 15434144
TI  - [Research on the contractile activity of intestinal smooth muscles; potentiation
      of the action of acetylcholine by ergotamine and barium salts].

PMID- 15434145
TI  - [Research on the contractile activity of isolated preparations of human large
      intestine and stomach].

PMID- 15434146
TI  - [Behavior of ascorbic acid added to macerates of liver of normal rats and of rats
      with liver in regeneration].

PMID- 15434147
TI  - [Quantitative method for study of the mechanical fragility of the erythrocytes].

PMID- 15434148
TI  - [First observations on the mechanical fragility of the erythrocytes in normal and
      thalassemic subjects].

PMID- 15434149
TI  - [Structural variations of lipids introduced into the peritoneum and their
      absorption].

PMID- 15434150
TI  - [In vitro behavior of the iodine number and of the saponification index of lipids
      extracted from the peritoneum after injection of emulsions of coconut oil].

PMID- 15434151
TI  - [Action of pituitary corticotropic hormone on the regeneration of the liver after
      partial hepatectomy].

PMID- 15434152
TI  - [Determination and distribution in the organism of chloromycetin].

PMID- 15434153
TI  - [CO2 does not possess antihistamine action in vitro].

PMID- 15434154
TI  - [Magnetic behavior of certain synthetic estrogens].

PMID- 15434155
TI  - [Behavior of the autonomic nervous system in pulmonary tuberculosis; clinical and
      pharmacodynamic examination].

PMID- 15434156
TI  - [Anatomo surgical application of Martino's craniometrolocalizer method for
      finding the middle meningeal artery].

PMID- 15434157
TI  - [Action of ultrasonic waves on the conductivity of electrolytic solutions].

PMID- 15434158
TI  - [Physical training. VI. Behavior of the erythrocyte count in man].

PMID- 15434159
TI  - [Physical training. VII. Behavior of the reticulocyte count in man].

PMID- 15434160
TI  - [Physical training. VIII. Effort myosis and its behavior during training in man].

PMID- 15434161
TI  - [Action of substances with antipermeabilizing activity on acute experimental
      pulmonary edema].

PMID- 15434162
TI  - [Importance of dysfunction of the arteriovenous anastomoses in determinism of
      shock].

PMID- 15434163
TI  - [Inhibitory effect of synthetic antihistamines on experimental
      desoxycorticosterone acetate polyarthritis].

PMID- 15434164
TI  - [Relations between neoplastic elements and fibrils of reticulin in
      reticulohistiocytary tumors].

PMID- 15434165
TI  - [Histamine content of the blood and of the skin and hematic eosinophilia in
      spontaneous scabies of the guinea pig].

PMID- 15434166
TI  - [Basal metabolism in subjects with hyperplasia of the thyroid in Perugia and
      vicinity].

PMID- 15434167
TI  - [Research in vitro on the activity of chloromycetin and aureomycin in the body
      fluids].

PMID- 15434168
TI  - [Diastase of skin and serum in induced hyperglycemia].

PMID- 15434169
TI  - [Biochemical significance of Robinow's method for localization of ribo- and
      desoxyribonucleic acids in the bacterial cell].

PMID- 15434170
TI  - [Variations of the cytoplasmatic content of ribonucleic acid during the evolutive
      phases of the bacterial cell].

PMID- 15434171
TI  - [The red pigment of a ligeid hemipteron, Pyrrochoris apterus].

PMID- 15434172
TI  - [Conjunctival reaction to histamine in normal pregnancy at term, in labor, and
      during puerperium].

PMID- 15434173
TI  - [Experimental contribution to the revelation of a viral factor in human
      leukemia].

PMID- 15434174
TI  - [Antibacterial activity of aureomycin and of chloromycetin in cerebrospinal
      fluid].

PMID- 15434175
TI  - [Evolution of experimental influenza in animals on a diet supplemented with
      purinic and pyrimidinic bases, with ribosonucleic acid and with sodium
      thymonucleinate].

PMID- 15434176
TI  - [Granulopexy and increase of permeability of the small vessels. II. Action of
      massive doses of histamine on the permeability and granulopexy of the endothelial
      cells of the small vessels].

PMID- 15434177
TI  - [Evolution of experimental influenza type A in animals on hypoproteic diet and on
      the same diet supplemented with certain amino acids].

PMID- 15434178
TI  - [Evolution of experimental influenza in animals on hyperlipid diet and in animals
      on the same diet supplemented with methionine].

PMID- 15434179
TI  - [Behavior of the liver lipids of Scorpaenae with alloxan diabetes treated with
      insulin].

PMID- 15434180
TI  - [Influence of cortical hormones on the course of the reconstructive processes in
      realimentation after fasting].

PMID- 15434181
TI  - [Studies on "rapid" types and "slow" types. V. Superior intelligence tests].

PMID- 15434182
TI  - [Temporal inversion of dreams due to sensory stimuli].

PMID- 15434183
TI  - [Granulopexy and increase of permeability of the small vessels. III. Duration of
      the action of neoantergan against the action of histamine on the small vessels of
      the skin].

PMID- 15434184
TI  - [Granulopexy and increase of permeability of the small vessels. IV. The increase
      of permeability of the small vessels during passive local cutaneous anaphylaxis
      of the guinea pig].

PMID- 15434185
TI  - [Pharmacological research on methionine. III. Methionine and experimental
      beriberi].

PMID- 15434186
TI  - [Pharmacological study of some pyrrolic derivatives. IV. General action of alpha
      beta-dimethyl-beta-pyrrolcarbonic acid, of alpha-beta'-dimethyl-alpha-acetyl-beta
      pyrrolcarbonic acid and of alpha-beta'-dimethyl-beta-acetyl-alpha'-pyrrolcarbonic
      acid on cold blooded animals].

PMID- 15434187
TI  - [Pharmacological study of some pyrrolic derivatives. V. General action of alpha
      alpha'-dimethyl-beta-pyrrolethylester].

PMID- 15434188
TI  - [Pharmacological study of some strychnine derivatives].

PMID- 15434189
TI  - [Action of some betains of strychnic acid and of the sulfates of the
      corresponding alkylated derivatives of strychnine on the isolated heart of Bufo
      vulgaris].

PMID- 15434190
TI  - [Significance of the plasmocyte reaction of the spleen and lymph nodes in the
      genesis of antibodies].

PMID- 15434191
TI  - [Action of synthetic dicoumarol on uterine and intestinal kinesis; experimental
      research].

PMID- 15434192
TI  - [Rh sensitization and abortion].

PMID- 15434193
TI  - [Experimental modifications of blood sugar in cancer of the uterus].

PMID- 15434194
TI  - [Hematic beta-glycerophosphatase activity in diphtheria of infants].

PMID- 15434195
TI  - [Presence of Leishman bodies in the nasal mucosa and mucus of infants with
      visceral leishmaniasis].

PMID- 15434196
TI  - [Effects of splenectomy on regeneration of the liver after partial hepatectomy].

PMID- 15434197
TI  - [Intradermal penicillin and bactericidal power of the blood].

PMID- 15434198
TI  - [Effect of chloromycetin on E. typhi in vitro].

PMID- 15434199
TI  - [Pathogenesis of microbial eczema].

PMID- 15434200
TI  - [Modification of Thunberg's technic for the study of tissue respiration].

PMID- 15434201
TI  - [Experiments with active and passive immunization in verruca plana juvenilis and
      verruca vulgaris].

PMID- 15434202
TI  - [Evaluation of liver function tests in the course of arsphenamine therapy].

PMID- 15434203
TI  - [Data on the symptomatology of superficial microsporiasis of the scalp].

PMID- 15434204
TI  - [Chronic ulceration of the leg treated with sympathectomy].

PMID- 15434205
TI  - [Methods for examination of aspecificity in syphilitic serodiagnostic tests
      (verification tests)].

PMID- 15434206
TI  - [Clinical aspects of the treatment and prevention of eczema, with special
      reference to occupational eczema].

PMID- 15434207
TI  - [Weber-Christian's panniculitis].

PMID- 15434208
TI  - [Studies on the anti-allergic effects of vitamin D2].

PMID- 15434209
TI  - [Four cases of Mucha-Hebermann's disease].

PMID- 15434210
TI  - [Peptic ulcer of the esophagus].

PMID- 15434211
TI  - [Nutrition in gestation].

PMID- 15434212
TI  - [Epidemic exanthematic diseases; their general prophylaxis].

PMID- 15434213
TI  - [Percentage of ticks carrying in nature, V.B., V.A.1 and V.A.2 strains of
      neotropic exanthematic typhus in Brazil].

PMID- 15434214
TI  - [Streptomycin therapy in granuloma venereum, with a case localized in the lower
      extremity].

PMID- 15434216
TI  - [Vital Brasil].

PMID- 15434215
TI  - [Importance of brucellosis. V. Social importance].

PMID- 15434217
TI  - [Routine versus indicated appendectomy in acute appendicitis].

PMID- 15434218
TI  - [Traumatic shock].

PMID- 15434219
TI  - [Osteoma--osteoid].

PMID- 15434220
TI  - [Treatment of retinitis pigmentosa with subcutaneous injections of melanophore
      hormone].

PMID- 15434221
TI  - Presidential address delivered at the Annual General Meeting of the British
      Dental Association.

PMID- 15434222
TI  - Valedictory address delivered at the Annual General Meeting of the British Dental
      Association.

PMID- 15434223
TI  - A study of some of the developmental, structural and pathological aspects of
      tubular hypoplasia in human enamel.

PMID- 15434224
TI  - An investigation into the removal of the four permanent molars.

PMID- 15434225
TI  - Short communications; acetomenaphthone in postoperative dental haemorrhage.

PMID- 15434226
TI  - Extensive endosteal osteoclastoma of the lower jaw.

PMID- 15434227
TI  - Malformation of an unerupted maxillary third molar.

PMID- 15434228
TI  - Orthodontics in general practice.

PMID- 15434229
TI  - Observations on experimental dental caries; does gonadectomy influence caries
      activity?

PMID- 15434230
TI  - Extensive complex composite odontome occupying the whole of the left maxilla.

PMID- 15434231
TI  - Local anaesthesia in conservative dentistry.

PMID- 15434232
TI  - Fibrinolysis induced by brain extracts.

PMID- 15434233
TI  - Investigations of the proteins released by surviving tissue; electrophoretic
      analysis of protein released by surviving liver and kidney slices.

PMID- 15434234
TI  - Restoration of the ability of some heated antisera to flocculate specifically
      their antigens.

PMID- 15434235
TI  - An easy method for counting bacterial colonies in roll tubes.

PMID- 15434236
TI  - Reactions of the reticular tissues to antigens.

PMID- 15434237
TI  - Mitotic activity in the shock state.

PMID- 15434238
TI  - Ascorbic acid and the production of antibody in the guinea-pig.

PMID- 15434239
TI  - The chemotherapy of experimental tuberculosis in mice.

PMID- 15434240
TI  - Variation in laboratory stocks of influenza viruses: biological characters of
      variants.

PMID- 15434241
TI  - Variation in laboratory stocks of influenza viruses: genetic aspects of the
      variations.

PMID- 15434242
TI  - The application of the conglutinating complement absorption test to virus
      systems.

PMID- 15434243
TI  - Quantitative studies in diphtheria prophylaxis: the second response.

PMID- 15434244
TI  - The iridescent phenomenon of Ps. pyocyanea.

PMID- 15434245
TI  - The toxicity of a product of reaction of mustard gas with serum proteins.

PMID- 15434246
TI  - Doctor and workman.

PMID- 15434247
TI  - Histological studies of the effects of beryllium oxide (glucine) on animal
      tissues.

PMID- 15434248
TI  - The toxicity of methyl iodide: I. Preliminary survey.

PMID- 15434249
TI  - The successful treatment of two recent cases of cyanide poisoning.

PMID- 15434250
TI  - The significance of Heinz bodies in the erythrocyte.

PMID- 15434251
TI  - Studies in occupational morbidity: part III.

PMID- 15434252
TI  - The water-drinking test.

PMID- 15434253
TI  - Permeability of the blood-aqueous barrier to fluorescein during the water
      drinking test in glaucomatous eyes.

PMID- 15434254
TI  - The arcuate lens opacities of mongolism and cataracts of similar appearance.

PMID- 15434255
TI  - The trabecula in chronic simple glaucoma with special reference to the
      gonioscopic appearance of blood in the canal of Schlemm.

PMID- 15434256
TI  - The significance of conjunctival aneurysms in diabetics.

PMID- 15434257
TI  - Intra-ocular involvement in a case of xanthomatous biliary cirrhosis.

PMID- 15434258
TI  - A case of watering eye due to pterygium.

PMID- 15434259
TI  - A non-magnetic foreign body extractor.

PMID- 15434260
TI  - Dark glasses.

PMID- 15434261
TI  - Physical medicine and rehabilitation in the United States of America, with
      special reference to the influence of the Baruch Committee on Physical Medicine
      and Rehabilitation in its development.

PMID- 15434262
TI  - Heating of the human maxillary sinus by microwaves.

PMID- 15434263
TI  - Electrotherapy.

PMID- 15434264
TI  - Some instruments used in ophthalmic practice; the objective examination of the
      refractive condition of the eye.

PMID- 15434265
TI  - The causes of errors of refraction.

PMID- 15434266
TI  - Eye movements.

PMID- 15434268
TI  - The limitations of orthoptics.

PMID- 15434267
TI  - A case of pseudo-glaucoma, with anisometropia.

PMID- 15434269
TI  - A combined method, obtaining fixation and pressure in the operation of skin
      grafting.

PMID- 15434270
TI  - Discussion of some problems of a case of chin reconstruction.

PMID- 15434271
TI  - Epiphora in facial paralysis.

PMID- 15434272
TI  - Reconstruction of the oesophagus.

PMID- 15434273
TI  - Correction of posterior urethral occlusion by epithelial inlay graft: case
      reports.

PMID- 15434274
TI  - Limitation of movement of mandible following trauma.

PMID- 15434275
TI  - The management of macroglossia when associated with prognathism.

PMID- 15434276
TI  - Operative correction by osteotomy of recessed malar maxillary compound in a case
      of oxycephaly.

PMID- 15434277
TI  - Pharyngoplasty by muscle transplantation.

PMID- 15434278
TI  - Primary hemangioma of the malar bone.

PMID- 15434279
TI  - Cases of chronic internal derangement of the temporo-mandibular joint treated by
      manipulation.

PMID- 15434280
TI  - The exposure method of treatment of burns.

PMID- 15434282
TI  - Neutron dose determination by the photographic plate method.

PMID- 15434281
TI  - The intensification of the fluorescent image in radiology.

PMID- 15434283
TI  - A new photographic material--a high-resolution emulsion for autoradiography.

PMID- 15434284
TI  - Observations concerning the secondary electronic emission from certain materials
      by means of its photographic action.

PMID- 15434285
TI  - Radiological features of Jackson's membrane.

PMID- 15434286
TI  - Intrapulmonary pleural effusion.

PMID- 15434287
TI  - Tomographic exploration of juxtapleural pulmonary pathology in extrapleural
      plombage.

PMID- 15434288
TI  - Method of determining the true angle of deviation in a fracture.

PMID- 15434289
TI  - RECOMMENDATIONS for the standardization of radiographs in industrial pulmonary
      diseases.

PMID- 15434290
TI  - The effect of nitrogen mustard on the growth of the froad bean root (Vicia faba).

PMID- 15434291
TI  - Some general problems in connection with the measurement of radioactivity in
      patients.

PMID- 15434292
TI  - Some applications of I131 and Na24 to clinical diagnoses.

PMID- 15434293
TI  - The application of radioactive isotopes in a case of multiple melanomata.

PMID- 15434294
TI  - Radioactive iodine in the diagnosis of thyrotoxicosis.

PMID- 15434295
TI  - The treatment of thyroid carcinoma by radioiodine.

PMID- 15434296
TI  - Results of treatment of thyroid cancer by radioactive iodine; a preliminary
      report.

PMID- 15434297
TI  - Therapeutic uses of radioactive isotopes in the Royal Cancer Hospital.

PMID- 15434299
TI  - Papillary carcinoma of renal pelvis.

PMID- 15434298
TI  - The use of radioisotopes in therapy.

PMID- 15434300
TI  - Lymphogranuloma venerium.

PMID- 15434301
TI  - Myositis ossificans progressiva.

PMID- 15434302
TI  - Diaphragmatic hernia complicated by gastric ulcer and pregnancy.

PMID- 15434303
TI  - Tracheal obstruction due to a foreign body.

PMID- 15434304
TI  - Multiple small bowel diverticula.

PMID- 15434305
TI  - The half-life of iodine131 and the anomalous decay of exposed sodium iodide
      sources.

PMID- 15434306
TI  - The care of the chronic sick; social and demographic data.

PMID- 15434307
TI  - The sex ratio of human births related to maternal age.

PMID- 15434308
TI  - The total lung volume and its subdivisions; a study in physiological norms; the
      effect of posture.

PMID- 15434309
TI  - GEORGE Ernest Gask.

PMID- 15434310
TI  - Smooth-muscle tumours of the gastro-intestinal tract.

PMID- 15434311
TI  - Successful resection of a large cavernous lymphangiomatoid lesion of the liver of
      a child aged 19 months.

PMID- 15434312
TI  - Volvulus of the stomach.

PMID- 15434313
TI  - Observations on bile-acid enteroliths with an account of a recent case.

PMID- 15434314
TI  - Sarcoma botryoides of the genital tract in female children.

PMID- 15434315
TI  - The value of the fibrinogen-B test in intravascular thrombosis in surgical
      subjects.

PMID- 15434316
TI  - Renal hydatid disease.

PMID- 15434317
TI  - Aortic embolectomy.

PMID- 15434318
TI  - Appendicitis--a report on its social pathology and recent surgical experience.

PMID- 15434319
TI  - Diverticula of the appendix and certain factors in their development.

PMID- 15434320
TI  - Changes in carcinoma of the breast following irradiation.

PMID- 15434321
TI  - Carcinoma of the cheek in a child aged eight years.

PMID- 15434322
TI  - The collateral circulation to the lungs.

PMID- 15434323
TI  - Chewing-gum vesical calculus in the male.

PMID- 15434324
TI  - The morphology of the branchial glomera and their tumours, with a report of a
      case of aortico-pulmonary glomus tumour.

PMID- 15434325
TI  - Enteroliths in a duodenal diverticulum.

PMID- 15434327
TI  - A case of trifid ureter and segmental hydro-ureter.

PMID- 15434326
TI  - Acute cholecystitis, in a child aged 4, treated by cholecystectomy; report of a
      case, with a brief review of the literature.

PMID- 15434328
TI  - Double gall-bladder; report of a case.

PMID- 15434329
TI  - Fulminating gangrene of the penis; report of a case.

PMID- 15434330
TI  - Leiomyosarcoma of the jejunum presenting as peritonitis.

PMID- 15434331
TI  - Accidental section and successful resuture of a bronchus.

PMID- 15434332
TI  - Gastric resection in situs inversus totalis.

PMID- 15434333
TI  - Perforated jejunal ulcer.

PMID- 15434334
TI  - 2,665 Cases of abortion; a clinical survey.

PMID- 15434335
TI  - Habitual abortion; prophylactic value of progesterone pellet implantation.

PMID- 15434336
TI  - Haematemesis and melaena.

PMID- 15434337
TI  - Haemorrhage from peptic ulcer; a report on 170 cases.

PMID- 15434338
TI  - Value of tuberculin-jelly test.

PMID- 15434339
TI  - Dietary treatment of hypertension.

PMID- 15434340
TI  - Effect of vitamin B12 on neuropathy in pernicious anaemia treated with folic
      acid.

PMID- 15434341
TI  - Prolonged retention of dead foetus in utero.

PMID- 15434342
TI  - Post-operative paralysis of the brachial plexus.

PMID- 15434343
TI  - Diagnosis and treatment of pernicious anaemia.

PMID- 15434344
TI  - Incidence and treatment of neurosis in industry.

PMID- 15434345
TI  - TRESPASS by a house-surgeon.

PMID- 15434346
TI  - INFECTIOUS diseases and vital statistics.

PMID- 15434347
TI  - FOOD-poisoning at Horden.

PMID- 15434348
TI  - POLIOMYELITIS.

PMID- 15434349
TI  - Medicine, science, and humanism; reflections on the first half of the twentieth
      century.

PMID- 15434350
TI  - A possible mode of transfer of infection by syringes used for mass inoculation.

PMID- 15434351
TI  - Diphyllobothrium infestation and anaemia in Great Britain.

PMID- 15434352
TI  - A specific serological type of Bact. coli found in infants' home in absence of
      epidemic diarrhoea.

PMID- 15434353
TI  - Bact. coli D 433 cases of diarrhoea in adults.

PMID- 15434355
TI  - Transfixion by a muck fork.

PMID- 15434354
TI  - Bone-marrow infusions: intratibial and intravenous routes compared.

PMID- 15434356
TI  - Chronic myeloid leukaemia and pregnancy.

PMID- 15434357
TI  - The problem of psoriasis.

PMID- 15434358
TI  - STREPTOMYCIN in otolaryngology.

PMID- 15434359
TI  - INFECTIOUS diseases and vital statistics.

PMID- 15434360
TI  - FOOD-poisoning at Horden.

PMID- 15434361
TI  - POLIOMYELITIS.

PMID- 15434362
TI  - Progress and trends in the science of anatomy.

PMID- 15434363
TI  - Amoebiasis in Great Britain, with special reference to carriers.

PMID- 15434364
TI  - Experimental burn studies, including treatment with cortisone-active material
      extracted from urine.

PMID- 15434365
TI  - Anomalous findings in differential diagnosis of jaundice by biochemical tests.

PMID- 15434366
TI  - Acute idiopathic porphyria; report of two cases.

PMID- 15434367
TI  - Poliomyelitis and immunization against whooping-cough and diphtheria.

PMID- 15434368
TI  - Simple method of treating injuries of the fingers.

PMID- 15434369
TI  - Congenital leukaemia.

PMID- 15434370
TI  - Carcinoma of the stomach.

PMID- 15434371
TI  - Epidemics, old and new.

PMID- 15434372
TI  - Controller for the all-glass syringe.

PMID- 15434373
TI  - Rigor mortis.

PMID- 15434374
TI  - INFECTIOUS diseases and vital statistics.

PMID- 15434375
TI  - POLIOMYELITIS.

PMID- 15434376
TI  - Reflections on criminal conduct and its treatment.

PMID- 15434377
TI  - Reactions produced by arthropods directly injurious to the skin of man.

PMID- 15434378
TI  - Division of popliteal vein in the treatment of so-called varicose ulceration.

PMID- 15434379
TI  - Toxic effects in animals and man after tetraethylammonium bromide.

PMID- 15434380
TI  - The management of head injuries from the anaesthetist's point of view.

PMID- 15434381
TI  - Congenital atresia of the oesophagus.

PMID- 15434382
TI  - Review of one year's work in Watford Pregnancy Diagnostic Centre.

PMID- 15434383
TI  - Use of the male British toad as a pregnancy test animal.

PMID- 15434384
TI  - Inversion of the uterus.

PMID- 15434385
TI  - Acquired sensitivity to thiopentone.

PMID- 15434386
TI  - The failing heart.

PMID- 15434387
TI  - Development of renal physiology; meeting of the renal association.

PMID- 15434388
TI  - Treatment of fractures of tibis and fibula.

PMID- 15434389
TI  - TRESPASS and assault.

PMID- 15434390
TI  - INFECTIOUS diseases and vital statistics.

PMID- 15434391
TI  - POLIOMYELITIS.

PMID- 15434392
TI  - ANTHRAX in cattle.

PMID- 15434393
TI  - Humanism, history, and natural science in medicine.

PMID- 15434394
TI  - Insulin-induced skeletal abnormalities in developing chickens.

PMID- 15434395
TI  - Mortality from and risk of gastric carcinoma among patients with pernicious
      anaemia.

PMID- 15434396
TI  - Haemolytic streptococcal gangrene of breast successfully treated with
      streptomycin.

PMID- 15434397
TI  - Rheumatic heart disease in service pensioners; a review of 318 cases.

PMID- 15434398
TI  - Decamethonium iodide as a curarizing agent in general anaesthesia.

PMID- 15434399
TI  - Volvulus of the small intestine.

PMID- 15434400
TI  - Aplastic anaemia complicating miliary tuberculosis.

PMID- 15434401
TI  - Treatment of typhoid carrier with penicillin and sulphamerazine.

PMID- 15434402
TI  - Sulphonamide therapy.

PMID- 15434403
TI  - STREPTOMYCIN in the treatment of tuberculosis meningitis.

PMID- 15434404
TI  - DOCTOR exonerated.

PMID- 15434405
TI  - INFECTIOUS diseases and vital statistics.

PMID- 15434406
TI  - POLIOMYELITIS.

PMID- 15434407
TI  - ANTHRAX in cattle.

PMID- 15434408
TI  - The way divides.

PMID- 15434409
TI  - CLINICAL trials of antihistaminic drugs in the prevention and treatment of the
      common cold; report by a special committee of the Medical Research Council.

PMID- 15434410
TI  - Trial of antistin in the common cold.

PMID- 15434411
TI  - Early clinical manifestations of disseminated sclerosis.

PMID- 15434412
TI  - After-history of successfully treated cases of subacute bacterial endocarditis.

PMID- 15434413
TI  - Congenital malaria.

PMID- 15434414
TI  - Fatal case of poisoning due to inhalation of methyl bromide.

PMID- 15434415
TI  - The internal spermatic fascia, with reference to repair of indirect inguinal
      hernia.

PMID- 15434416
TI  - Parathion poisoning.

PMID- 15434417
TI  - Auricular fibrillation after electric convulsion therapy.

PMID- 15434418
TI  - Survival of a 16-oz. baby.

PMID- 15434419
TI  - Chemotherapy. I. Administration of penicillin.

PMID- 15434420
TI  - Infant-feeding in north-east Africa.

PMID- 15434421
TI  - INFECTIOUS diseases and vital statistics.

PMID- 15434422
TI  - POLIOMYELITIS.

PMID- 15434423
TI  - Methods of education.

PMID- 15434424
TI  - The art of lecturing.

PMID- 15434426
TI  - The training of clinical teachers.

PMID- 15434425
TI  - Methods and men in the teaching of clinical medicine.

PMID- 15434427
TI  - Clinical evaluation of effects of drugs on medical students as a teaching method.

PMID- 15434428
TI  - Some mechanical aids to instruction.

PMID- 15434429
TI  - A G.P. on his clinical training.

PMID- 15434430
TI  - SOME comments on medical education in Great Britain by a London medical student.

PMID- 15434431
TI  - Spontaneous amputation of cervix.

PMID- 15434432
TI  - POSTGRADUATE education in London.

PMID- 15434433
TI  - LONDON undergraduate schools.

PMID- 15434434
TI  - POSTGRADUATE courses outside London.

PMID- 15434436
TI  - QUALIFYING degrees and diplomas.

PMID- 15434435
TI  - UNIVERSITY medical centres outside London.

PMID- 15434437
TI  - ENROLLMENT in medicine.

PMID- 15434438
TI  - TRAINING of pathologists.

PMID- 15434439
TI  - TRAINING courses in psychiatry.

PMID- 15434441
TI  - MEDICAL schools at Oxford and Cambridge.

PMID- 15434440
TI  - PROFESSIONAL training of Army Medical Officers.

PMID- 15434442
TI  - SCOTTISH and Irish schools.

PMID- 15434443
TI  - VISUAL education.

PMID- 15434444
TI  - SPECIAL diplomas.

PMID- 15434445
TI  - MEDICAL societies.

PMID- 15434446
TI  - EMPIRE Medical Advisory Bureau.

PMID- 15434447
TI  - SERVICE overseas.

PMID- 15434448
TI  - SYRIAN University, Faculty of Medicine.

PMID- 15434449
TI  - POLIOMYELITIS.

PMID- 15434450
TI  - INFECTIOUS diseases and vital statistics.

PMID- 15434451
TI  - Effects of hypervitaminosis A on foetal mouse bones cultivated in vitro;
      preliminary communication.

PMID- 15434452
TI  - Respiratory studies in paralytic poliomyelitis.

PMID- 15434453
TI  - Poisoning by organic phosphorus insecticides.

PMID- 15434454
TI  - Food-poisoning in Sheffield in 1949.

PMID- 15434455
TI  - Thrombocytopenic purpura due to quinidine.

PMID- 15434456
TI  - Ollier's disease: dyschondroplasia.

PMID- 15434457
TI  - Lysivane therapy for parkinsonism.

PMID- 15434458
TI  - Relative incidence of gastric and duodenal ulcers.

PMID- 15434459
TI  - Chronic subdural haemorrhage associated with schizophrenic reaction.

PMID- 15434460
TI  - Poliomyelitis.

PMID- 15434461
TI  - Porphyrin metabolism and porphyria.

PMID- 15434462
TI  - INFECTIOUS diseases and vital statistics.

PMID- 15434463
TI  - Subacute bacterial endocarditis with pulmonary embolism in a horse associated
      with Shigella equirulis.

PMID- 15434464
TI  - Electroplectic anaesthesia in animals and man.

PMID- 15434465
TI  - Developing tendencies in mastitis therapy.

PMID- 15434466
TI  - Brucella abortus infection in diary cattle in Singapore.

PMID- 15434467
TI  - Electroplectic anaesthesia in animals and man.

PMID- 15434468
TI  - Experiments with dried bracken (Pteris aquilina).

PMID- 15434469
TI  - [Short wave d'arsonvalization in gynecology].

PMID- 15434470
TI  - [Basedowism or hyperthyroidism due to bacillary infection].

PMID- 15434471
TI  - [Voluminous hematometra due to diffuse sarcoma of the endometrium].

PMID- 15434472
TI  - [Social service].

PMID- 15434473
TI  - [Effect of suboccipital injection of streptomycin on respiration and blood
      pressure].

PMID- 15434474
TI  - [Basedow's disease after castration: psychosomatic complications].

PMID- 15434475
TI  - [Role of surgery in pulmonary tuberculosis].

PMID- 15434476
TI  - [Not Available].

PMID- 15434477
TI  - [Chemical diagnosis of pregnancy by the determination of histidine in the urine].

PMID- 15434478
TI  - [Clinical results obtained by the determination of histidine in the urine].

PMID- 15434479
TI  - [Arterial sympathosis].

PMID- 15434480
TI  - [The dangerous universal donor].

PMID- 15434481
TI  - [The activity of the blood transfusion service of the Belgian Red Cross].

PMID- 15434482
TI  - [High dosage of vitamin C and antibiotics].

PMID- 15434483
TI  - [Recent studies on saturnism in Italy].

PMID- 15434484
TI  - [Appendicitis and urology].

PMID- 15434485
TI  - [Chronic non-tuberculous sacro-iliac arthritis].

PMID- 15434486
TI  - [Some new aspects of research on blood groups].

PMID- 15434487
TI  - [Control of the progress of thrombo-embolic disease and its treatment during the
      puerperium].

PMID- 15434488
TI  - [Four years of medical supervision of the flight personnel of an important air
      line].

PMID- 15434489
TI  - [Memory of Gustave Roussy].

PMID- 15434490
TI  - [Spontaneous hypophyseal tumors in the rat].

PMID- 15434491
TI  - [Cancerous cells in electronic microscope].

PMID- 15434492
TI  - [Study of the effect of radium on epitheliomas of the uterus; radiologic and
      histologic data].

PMID- 15434493
TI  - [Critical study of cancer apparently due to skin puncture injuries].

PMID- 15434494
TI  - [Estrogenic substances in normal or pathologic tissue; research].

PMID- 15434495
TI  - [Frequency of cancer according to localization and sex at the Institute of Radium
      in Cuba].

PMID- 15434496
TI  - [Precancerous lesions and functional disorders of the frog skin due to cyclic
      cancerogenous hydrocarbons].

PMID- 15434497
TI  - [Effect of fetal death on the permeability of ovarian membranes to inulin; an
      unpublished clinical test for the diagnosis of fetal death in utero].

PMID- 15434498
TI  - [Bracht method].

PMID- 15434499
TI  - [Analgesia in normal obstetrics].

PMID- 15434500
TI  - [Unexplained pneumoperitoneum in pregnancy with intestinal occlusion].

PMID- 15434501
TI  - [Primary tubal epithelioma].

PMID- 15434502
TI  - [Case of thrombophlebitis following cesarean section, treated with anticoagulants
      and antibiotics].

PMID- 15434503
TI  - [New instrument to replace the forceps].

PMID- 15434504
TI  - [Mechanism of postoperative uterine hemorrhages].

PMID- 15434505
TI  - [Action of oxygen and carbon dioxide on uterine contraction and on its pain
      threshold].

PMID- 15434506
TI  - [Easy rapid method of blood count in pregnancy and labor].

PMID- 15434507
TI  - [Mole with intraperitoneal hemorrhage due to an intravascular implant of a
      syncytial embolism].

PMID- 15434508
TI  - [Radical treatment of extensive genital prolapse; 15 cases of colpohysterectomy
      with vesicorectal fixation].

PMID- 15434509
TI  - [Dystocia due to cicatricial stenosis of the cervix caused by cauterization with
      a Filhos pencil; cesarean section; new pregnancy followed by spontaneous labor].

PMID- 15434510
TI  - [Lipoid nephrosis; nephritis in pregnancy and the Rh factor].

PMID- 15434511
TI  - [Case of genital tuberculosis treated with streptomycin pre- and
      postoperatively].

PMID- 15434512
TI  - [Pregnancy and parturition following conservative surgery for the utero-adnexal
      apparatus].

PMID- 15434513
TI  - [Use of streptomycin in puerperal and cesarean infections].

PMID- 15434514
TI  - [Atypical hyperplasia of the endometrium and cancer of the corpus uteri].

PMID- 15434515
TI  - [Dry gangrene in the newborn with spontaneous amputation of the lower extremity].

PMID- 15434516
TI  - [Case of dystocia due to a bilateral polycystic disease in a monstrous fetus;
      cesarean section for a dead fetus..].

PMID- 15434517
TI  - [Intestinal malformations and fetal peritonitis].

PMID- 15434518
TI  - [Two cases of pregnancy after utero-ovarian irradiation producing amenorrhea].

PMID- 15434519
TI  - [Two new cases of simultaneous intra- and extrauterine pregnancy].

PMID- 15434520
TI  - [A symmelus monster].

PMID- 15434521
TI  - [Four Strassmann operations for uterus septus of which one was followed by
      pregnancy and normal parturition].

PMID- 15434522
TI  - [Tumors of the corpus uteri; necessity of systematic examination].

PMID- 15434523
TI  - [Importance of the associated study of the elimination of gonadotropic hormones
      and of pregnandiol in women threatened with abortion].

PMID- 15434524
TI  - [Decrease of gonadotropic hormones in the hours following parturition, determined
      by the standard Rana esculenta test].

PMID- 15434525
TI  - [Case of Biermer's anemia disclosed after parturition and treated with vitamin
      B12].

PMID- 15434526
TI  - [Syphilis in pregnancy].

PMID- 15434527
TI  - [Enormous ovarian cyst and pregnancy].

PMID- 15434528
TI  - [Case of cicatricial stenosis of the vagina].

PMID- 15434529
TI  - [Amenorrhea, genital hormone therapy and ovarian endometriosis].

PMID- 15434530
TI  - [Spontaneous rupture of the rectus abdominis in the 5th month of pregnancy].

PMID- 15434531
TI  - [Clinical description of several cases of postoperative abdominal extenso
      progressive syndromes; their place in the general picture of extenso-progressive
      syndromes].

PMID- 15434532
TI  - [Case of lipoma of the uterus].

PMID- 15434533
TI  - [Series of 90 cases of tumors of the uterus; diagnosis and treatment].

PMID- 15434534
TI  - [Technic in interruption of pregnancy].

PMID- 15434535
TI  - [Treatment of cancer of the vulva].

PMID- 15434536
TI  - [Post abortum anuria; peritoneal dialysis; cure].

PMID- 15434537
TI  - [Post abortum septicemia a perfringens].

PMID- 15434538
TI  - [Normal sex differentiation and hormonal conditioning. Early somatic sex
      characteristics, genital tubercle and syrinx, in a duck embryo].

PMID- 15434539
TI  - [Study of Phasiinae cimicophagous (Diptera larvaevoridae). X. "Offensive mimesis"
      of Allophora and Gymnosoma].

PMID- 15434540
TI  - [Rhythm of the tide of Chromulina psammophile].

PMID- 15434541
TI  - The European background of the young Dr. Welch.

PMID- 15434542
TI  - Comments on the relation of Dr. Welch to the rise of microbiology in America.

PMID- 15434543
TI  - Dr. Welch and medical history.

PMID- 15434544
TI  - Reminiscences of the summer semester, 1877, at Breslau.

PMID- 15434545
TI  - The historical relationship between the concept of tumor and the ending -oma.

PMID- 15434546
TI  - The death of President Garfield.

PMID- 15434547
TI  - Simon Newcomb and the location of President Garfield's bullet.

PMID- 15434548
TI  - The circular motion of the blood and Giordano Bruno's philosophy of the circle.

PMID- 15434549
TI  - The anticholinesterase activity in vitro of the insecticide parathion (p
      nitrophenyl diethyl thionophosphate).

PMID- 15434550
TI  - The toxic effects in man of the anticholinesterase insecticide parathion (p
      nitrophenyl diethyl thionophosphate).

PMID- 15434551
TI  - The determination and significance of substances neutralizing Newcastle virus in
      human serum.

PMID- 15434552
TI  - Depression of synaptic transmission through sympathetic ganglia following
      temporary occlusion of the aorta: an effect of endogenous adrenalin.

PMID- 15434553
TI  - The appearance of vitamin B12 activity in urine after oral and intramuscular
      administration to man.

PMID- 15434554
TI  - Studies of terramycin, in vivo and in vitro.

PMID- 15434555
TI  - Phosphatase activity of cartilage and periosteum with various substrates.

PMID- 15434556
TI  - The ability of ACTH and cortisone to alter delayed type bacterial
      hypersensitivity.

PMID- 15434557
TI  - Studies of the metabolism of the human placenta; oxygen consumption and anaerobic
      glyolysis in relation to aging and severe toxemia.

PMID- 15434558
TI  - The correlation between the ear thickness and saturation readings of the Millikan
      oximeter.

PMID- 15434559
TI  - The effects of posterior pituitary extract and smoking on water, sodium and
      chloride excretion in normal subjects and in patients with congestive cardiac
      failure.

PMID- 15434561
TI  - [Cushing's syndrome].

PMID- 15434560
TI  - A method for recording ballistocardiographic vectors; preliminary report.

PMID- 15434562
TI  - [Functional examination of the adrenal cortex].

PMID- 15434563
TI  - [Recent applications of estrogens in therapy].

PMID- 15434565
TI  - [Treatment of brucellosis].

PMID- 15434564
TI  - [Hormonal treatment of chronic rheumatism].

PMID- 15434566
TI  - [Radiologic examination in the diagnosis of cancer of the bronchus].

PMID- 15434567
TI  - [Double primary cancer of the stomach].

PMID- 15434568
TI  - [The voices of Joan of Arc are inner voices].

PMID- 15434569
TI  - [Tularemia].

PMID- 15434570
TI  - [Lobstein's disease].

PMID- 15434571
TI  - [The mammary gland and puberty; attempted quantitative interpretation of the
      phenome na of puberty].

PMID- 15434572
TI  - Is there a relationship in pathogenesis between arteriosclerosis and familial
      hypercholesteremia?

PMID- 15434573
TI  - Clinical cardiology vs. the electrocardiogram.

PMID- 15434574
TI  - ACTH therapy in bronchial asthma; histamine and methacholine tolerance in the
      acute experiment and during prolonged treatment.

PMID- 15434575
TI  - Problems of diffusion in the lungs.

PMID- 15434576
TI  - Extramedullary hemapoiesis; myeloid metaplasia.

PMID- 15434577
TI  - Interactions of proteins and small molecules in relation to medicine.

PMID- 15434578
TI  - Comparison of tests of thyroid function.

PMID- 15434579
TI  - Thyrotropic exophthalmos.

PMID- 15434580
TI  - Diabetic neuropathy.

PMID- 15434581
TI  - Advances in the diagnosis of bacterial infections.

PMID- 15434582
TI  - [Vitamins and their interrelations; views and aspects of the problem].

PMID- 15434583
TI  - [Metabolism of beta-alanine in the animal kingdom].

PMID- 15434584
TI  - [Metabolism of beta-amino-butyric and beta-amino-valeric acid].

PMID- 15434585
TI  - [Partition microchromatography of alkaloids and of various biological nitrogenous
      bases. II. Utilization of acid solvent phases; chromatographic importance of the
      dissociation constant of alkaloids].

PMID- 15434586
TI  - [Research on lipids accompanying serum globulins and albumins during their
      separation by various organic salts and solvents].

PMID- 15434587
TI  - [Effect of delipidation of immune serums on their serological action].

PMID- 15434588
TI  - [Study of acid hydrolysis of lysozyme. Possibility of avoiding destruction of
      tryptophan during hydrolysis].

PMID- 15434589
TI  - [Study of protein precipitation of differently treated human plasma].

PMID- 15434590
TI  - [Substitute technic for electrophoretic precipitation of proteins].

PMID- 15434591
TI  - [Research on the vitamin A factors of the oils of Penaeidae].

PMID- 15434592
TI  - [Study of a skeleton of a pig following a hyperphosphoric diet].

PMID- 15434593
TI  - [Relation between chemical structure and estrogenic action of organic molecules].

PMID- 15434594
TI  - [Metabolism of triphenylethylene bromide, observed in the mouse with the aid of
      radioactive tracers].

PMID- 15434595
TI  - [Meso-inositol and cell division. I. Effect of mesoinositol on the growth and
      mitosis of higher plants].

PMID- 15434596
TI  - [Meso-inositol and cell division. II. Influence of meso-inositol on the mito
      catalytic effect of colchicine].

PMID- 15434597
TI  - [Method of determination of CO2 in pulverized solids].

PMID- 15434598
TI  - [Photometric determination of histamine by diazo reaction].

PMID- 15434599
TI  - [Enzymes and the vital cycle of plants].

PMID- 15434600
TI  - [Research on phytase. XV. Comparative study of acidic and phytasic hydrolysis of
      phytic acid].

PMID- 15434601
TI  - [Research on phytase. XVI. Study of compounds obtained after partial hydrolysis
      of phytic acid].

PMID- 15434602
TI  - [Phosphatase in the hydrolysis of starch paste].

PMID- 15434603
TI  - [Diastatic hydrolysis of glucofructosans: hypothesis of complex enzyme substratum
      formation].

PMID- 15434604
TI  - [Chemical composition of a Mediterranean ericace: Arbutus unedo L..].

PMID- 15434605
TI  - [Rutoside and reactions of tannins].

PMID- 15434606
TI  - [Effect of N/30 soda on tobacco mosaic virus and on nucleic acid of virus so
      liberated. I. Demonstration a factor accelerating the loss of precipitate ability
      of nucleic acid and the formation of diffusible products].

PMID- 15434607
TI  - [Study of phosphorus metabolism in Sterigmatocystis nigra. VI Role of phosphorus
      and its principal biochemical forms in the course of growth].

PMID- 15434608
TI  - [The fate of globulin fractions of plasma in the course of delipidation].

PMID- 15434609
TI  - [Biochemical study of the Bence-Jones protein; determination and analysis of
      methionine].

PMID- 15434610
TI  - [Study of the combination of copper with glutathione].

PMID- 15434611
TI  - [Evaluation of cellular water; behaviour of yeast subjected to variations of
      external medium].

PMID- 15434612
TI  - [Colorimetric microdetermination of blood magnesium by 8-hydroxyquinolene].

PMID- 15434613
TI  - [Microdetermination of adrenaline].

PMID- 15434614
TI  - [False synovial cysts of the fingers: synovial lesion].

PMID- 15434615
TI  - [Remarkable efficacy of the Tommasi treatment (sodium salicylate) in subacute and
      chronic lupus erythematosus].

PMID- 15434616
TI  - [Erythema due to phenolphthalein].

PMID- 15434617
TI  - [A certain case of reinfection and a probable case of clinica and serological
      recurrence after treatment with massive doses of penicillin].

PMID- 15434618
TI  - [Thyroid insufficiency in pemphigus foliaceus].

PMID- 15434619
TI  - [Frontal osteitis of gummous aspect contemporaneous with the roseola].

PMID- 15434620
TI  - [A pseudo false reaction of syphilis].

PMID- 15434621
TI  - [A case of cutaneous lymph node leprosy].

PMID- 15434622
TI  - [False positive reactions of syphilis in infectious mononucleosis].

PMID- 15434623
TI  - [Role of the port of entry in the transmission of syphilis to the mouse].

PMID- 15434625
TI  - [Treatment of ulcers of the leg by orthobiotic serum].

PMID- 15434624
TI  - [Polymorphic bullous erythema; toxicoderma; efficacy of vitamin B2].

PMID- 15434626
TI  - [Granuloma annulare and collagen diseases].

PMID- 15434627
TI  - [Canine mange transmitted to man and persistent].

PMID- 15434628
TI  - [Aureomycin; 2 cases of erythema multiforme].

PMID- 15434629
TI  - [Cutaneous lesions in chronic arsenic poisoning].

PMID- 15434630
TI  - [Total loss of hair, during psychotherapy of an obsession neurosis].

PMID- 15434631
TI  - [Besnier-Boeck-Schaumann disease in large annular plaques with a follicular
      eruption at the periphery].

PMID- 15434632
TI  - [Generalized granuloma annulare, clinically typical, histologically atypical,
      improved by bismuth therapy].

PMID- 15434633
TI  - [Dystrophic epidermolysis bullosa in a congenital syphilitic].

PMID- 15434634
TI  - [Two cases of cutaneous tuberculosis treated with orally administered
      streptomycin and PAS].

PMID- 15434635
TI  - [Pityriasis cacheticorum in amelioration; probable (occupational arsenic
      poisoning)].

PMID- 15434636
TI  - [Bullous dermatoses and aureomycin].

PMID- 15434637
TI  - [Subacute dermatomyositis with verrucous tuberculoid elements].

PMID- 15434638
TI  - [Pathological relationships of the inclusion urethritis syndrome: Reiter's
      syndrome, atypical pneumonia, pneumopathies with positive syphilitic serology of
      the Franconi type].

PMID- 15434639
TI  - [Streptomycin in the treatment of leprosy].

PMID- 15434640
TI  - [Results of the examination of 1340 primary-secondary syphilitics who followed
      regular arsenobismuth and bismuth treatment for a minimum of 4 years].

PMID- 15434641
TI  - [Respective relation of various tinea capitis observed over a 3-year period].

PMID- 15434642
TI  - [Treatment of sclerous hypodermitis of the legs with tocopherol].

PMID- 15434643
TI  - [A case of guttate parapsoriasis associated with papulo-necrotic tuberculids].

PMID- 15434644
TI  - [Pigmented nevus of late appearance succeeding a herpetic lesion of the lower
      lip].

PMID- 15434646
TI  - [Limitations of use of sulfone in treatment of leprosy].

PMID- 15434645
TI  - [Intolerance to stovarsol; stovarsolids].

PMID- 15434647
TI  - [Epidemiology of tinea in the Lyon area in the last few years].

PMID- 15434648
TI  - [Undecylenic acid in the treatment of epidermomycosis and ringworm].

PMID- 15434649
TI  - [Cutaneo-mucous accidents during chloromycetin treatment in a typhoid service].

PMID- 15434650
TI  - [Non-enzymatic oxidation with special reference to the problem of melanogenesis].

PMID- 15434651
TI  - [Multiple gangrene of the skin of the lower extremities, recurrent, very painful,
      afebrile, chronic; pyretotherapy; cure].

PMID- 15434652
TI  - [Tissue therapy; review of principles; chemical study].

PMID- 15434653
TI  - [New dermatological excipient].

PMID- 15434654
TI  - [Tibial periostitis with multiple transverse striae of an old osteochondritis
      without any bismuth therapy in either mother or child].

PMID- 15434655
TI  - [Radiography in two cases of Parrot's pseudoparalysis; evolution and treatment].

PMID- 15434656
TI  - [Pluri-sensitization to antibiotics].

PMID- 15434657
TI  - [Syphilitic reinfection three times in the same individual].

PMID- 15434658
TI  - Antibiotics and sulfonamides in the treatment of trachoma.

PMID- 15434659
TI  - Lymphogranuloma venereum; a general review.

PMID- 15434660
TI  - Epidemiology of Q fever.

PMID- 15434661
TI  - Bilharziasis as a public health problem in the Pacific.

PMID- 15434662
TI  - Notes on a collection of fleas from Peru.

PMID- 15434663
TI  - Malaria along the Mexico-United States border.

PMID- 15434664
TI  - Observations on the density of Phlebotomus populations following DDT campaigns.

PMID- 15434665
TI  - Residual DDT content a rapid method for the detection and determination of small
      quantities of DDT on sprayed surfaces.

PMID- 15434666
TI  - Standardization of serological tests for the diagnosis of the typhus group of
      fevers.

PMID- 15434667
TI  - Standardization of diagnostic agglutination tests; typhoid and paratyphoid A and
      B fevers.

PMID- 15434668
TI  - Standardization of liver extracts.

PMID- 15434669
TI  - Third international digitalis standard.

PMID- 15434670
TI  - Control of plague in Taranto, Italy, 1945-1946; an account of a successful
      programme of rodent extermination.

PMID- 15434671
TI  - Complement-fixation reactions with cardiolipin antigen compared with Kahn
      reactions.

PMID- 15434672
TI  - Survey of venereal diseases in Afghanistan.

PMID- 15434673
TI  - Detection of the tubercle bacillus; survey of current laboratory procedure.

PMID- 15434674
TI  - Trend of infant mortality in Iceland.

PMID- 15434675
TI  - Contributions of statistics to world health.

PMID- 15434676
TI  - Psychiatric examination of offenders.

PMID- 15434677
TI  - [Association of ductus arteriosus and aortic coarctation; two variants].

PMID- 15434678
TI  - [Xanthomatous cirrhosis].

PMID- 15434679
TI  - [Spontaneous hypoglycemia; manifestation of adrenal cortex insufficiency in 2
      cases].

PMID- 15434680
TI  - [Lipiodol penetration into the paravertebral lymph nodes following hysterography
      with reference to certain lumbo-sacral pains in women].

PMID- 15434681
TI  - [Study of three cases of visceral actinomycosis with multiple foci of pulmonary
      predominance].

PMID- 15434682
TI  - [Pleural hemorrhagic effusion with local and medullary eosinophilia and without
      marked eosinophil cells in the blood].

PMID- 15434683
TI  - [A fatal case of thoracic blastomycosis with invasion of the spinal canal].

PMID- 15434684
TI  - [Study of 2 cases of alkaptonuria].

PMID- 15434685
TI  - [Research in antidiuretic hormone and its distribution in the organism during
      certain pathological conditions].

PMID- 15434686
TI  - [Frontal, internal hyperostosis and hyperfolliculinism].

PMID- 15434687
TI  - [Meningioma of the right paracentral lobe with massive hyperalbuminosis;
      resection].

PMID- 15434688
TI  - [A case of benzolic hemopathy treated by blood transfusion, penicillin and
      spongiosa transplants].

PMID- 15434689
TI  - [Several cases of exanthematous typhus, Chloromycetin treatment].

PMID- 15434690
TI  - [Variations in the antihistaminic properties of serum during the menstrual
      cycle].

PMID- 15434691
TI  - [Infectious jaundice caused by paratyphoid B bacilli; favorable action of
      chloromycetin].

PMID- 15434692
TI  - [Recurrent meningeal hemorrhage with a cerebral angiome; recovery after excision;
      efficacy of radiotherapy in arterial angiome].

PMID- 15434693
TI  - [Endocrine syndrome in an adult with neural heredosyphilis].

PMID- 15434694
TI  - [The heart of asthmatics].

PMID- 15434695
TI  - [Angiopneumography and bronchial cancer].

PMID- 15434696
TI  - [Clinical study of an unilateral bulbo-pontopeduncular syndrome; recovery;
      vascular modifications; probably responsible for this syndrome].

PMID- 15434697
TI  - [Herpes zoster in cancerous subjects].

PMID- 15434698
TI  - [Case of lead colic with marked disorders in porphyrin metabolism and normal lead
      content in blood].

PMID- 15434699
TI  - [Raynaud's syndrome in menopause and calculus].

PMID- 15434700
TI  - [Acute phases of chronic lupus erythematosus: Kaposi-Besnier-Libmann-Sachs
      syndrome, which appeared cured by streptomycin but was followed by nephritis,
      uremia and death].

PMID- 15434701
TI  - [Treatment of primary and secondary syphilis in adults by 15 million units of
      penicillin preceded by an injection of mercuric cyanide; statistics after 3
      years].

PMID- 15434702
TI  - [Broncho-pulmonary manifestations of costal osteomyelitis].

PMID- 15434703
TI  - [Sudden cure of inflammatory, chronic polyarthritis after the enervation of the
      carotid sinus].

PMID- 15434704
TI  - The surgical treatment of portal hypertension.
AB  - Portacaval shunt operations were done in 15 of 18 patients who were treated
      surgically for portal hypertension. In eight cases the shunt was established by
      splenorenal anastomosis; in seven by anastomosis of the portal vein to the side
      of the inferior vena cava. Of the eight patients with splenorenal shunt, two are
      well, four are considered improved, and two have died. Of the seven in whom the
      portal vein was joined to the vena cava, two are improved, one is unimproved, and
      four have died.

PMID- 15434706
TI  - The preoperative and postoperative care of acute arterial obstruction.
AB  - Acute arterial obstruction may result not only from arterial injuries but also
      from thrombosis or embolism. The fate of the extremity is generally decided in
      the first few hours following the obstruction of the major artery. It is
      therefore essential that physicians should be able to recognize acute ischemia of
      the extremities and institute treatment which will prevent permanent damage and
      facilitate the reestablishment of normal circulation. Direct application of heat
      should be scrupulously avoided since the reduced blood flow is unable to supply
      increased metabolic demand. The extremity should be placed at or just below heart
      level so as to avoid both the ischemia of elevation and the edema of dependency.
      Pressure in the form of either encircling plaster or even compression bandages
      should be avoided and the extremity simply immobilized by a posterior splint.
      General supportive treatment is essential to maintain adequate pressure and
      composition of the arterial blood. In selected cases, agents to overcome vascular
      spasm or to prevent extension of intravascular thrombosis are indicated.

PMID- 15434705
TI  - The use of aerosol penicillin and streptomycin in bronchopulmonary infections.
AB  - Three hundred patients with subacute or chronic non-tuberculous bronchopulmonary
      disease were given aerosol therapy, chiefly penicillin and more recently
      penicillin combined with streptomycin. The result showed that the inhalation of
      these antibiotics is a useful procedure in the treatment of tracheobronchitis,
      either subacute or protracted, or in association with bronchial asthma,
      bronchiectasis or pulmonary emphysema. The method of administration is simple.

PMID- 15434707
TI  - Relation of the adrenal cortex to immunizing mechanisms.
AB  - Experimental evidence is available to support the general conclusion that
      pituitary-adrenocortical secretion may have an important regulatory role in
      immunizing mechanisms, including antigen-antibody relationships and the state of
      tonus of the ground substance of the mesenchyme. The specific contributions of
      other processes affected by pituitary-adrenocortical secretion to immunizing
      mechanisms remain to be elucidated.

PMID- 15434708
TI  - Care of the neglected burn patient.
AB  - In spite of widely dispersed modern knowledge of burn treatment, neglect or inept
      care of severely burned patients continues as a cause of a considerable medical
      problem. Since the neglected patient is usually emaciated, pain-ridden and low in
      morale, prompt attention to rehabilitation through blood transfusions,
      nourishment, relief of pain and cleansing of the wound is mandatory. Skin
      grafting as soon as possible is the aim.

PMID- 15434709
TI  - Comparative concurrent results of vagotomy procedures, conventional gastric
      resection and hemigastrectomy with subtotal vagotomy.
AB  - The question of the best surgical treatment of duodenal ulcer remains unanswered.
      In a series of 132 patients, results following gastric resection and
      hemigastrectomy with subtotal vagotomy were better than those following vagotomy
      procedures alone.

PMID- 15434710
TI  - Indications for different approaches to prostatectomy.
AB  - Most urologists are definite and positive in their conviction as to which
      approach to prostatectomy is indicated in a given case. Their views are often so
      widely divergent that other physicians may be confused as to the best advice to
      give patients who need prostatic operation. Urologists who extol one approach or
      technique and deride another only add to the confusion and prejudice. The most
      important indication for the use of any approach or technique is the ability of
      the surgeon to carry it out.

PMID- 15434711
TI  - Atopic dermatitis-etiology and clinical management.
AB  - Atopic dermatitis is primarily an allergic problem, similar in most of its
      aspects to that of allergic bronchial asthma. It should be studied and treated
      like asthma, with especial emphasis on the significance of inhalant allergens. It
      is doubtful that psychic factors are of importance in primary genesis of the
      disease although they may be involved in exacerbation of it.

PMID- 15434712
TI  - Intracranial angiography in the treatment of cerebral vascular accidents; reports
      of cases and a review of the literature.
AB  - Five cases of intracerebral hematoma, including one case of calcified
      intracerebral hematoma, are presented and treatment is discussed. The role of
      carotid arteriography, stellate ganglion blocks, vasodilator drugs and operation
      in the treatment of cerebral vascular accidents is discussed and typical cases of
      the various vascular anomalies of the cerebral vascular system are presented.

PMID- 15434713
TI  - Carcinoma of the cervix.
AB  - Studies by eminent surgeons to reevaluate the place of radical operations in the
      treatment of carcinoma of the cervix-now that extensive procedures have become
      less hazardous-apparently have led to confusion in some minds as to choice
      between surgical and radiation therapy. Pending outcome of the studies, general
      employment of surgical treatment is unwarranted. Radiation is the treatment of
      choice in most cases, particularly if the lesion is in an early stage, although
      radical operation is indicated in certain rare early cases in which delivery of
      an effective dose of radiation to involved areas is technically difficult.
      Elsewise it appears at present that operation should be used only in cases of
      stages III or IV carcinoma-in which results by either means of treatment are
      poor.One hundred and seven patients were treated with a combination of x-ray and
      radium irradiation. X-ray was used first to reduce the hazard of implanting the
      radium. The "five-year arrest" rates were as follows: For 22 patients with stage
      I lesion, 70 per cent; for 31 with stage II, 55.7 per cent; 33 with stage III,
      39.7 per cent; 21 with stage IV, 0. Eighteen patients with diagnosis of carcinoma
      of the cervix who had had subtotal hysterectomy were treated. The stage of the
      disease could not be determined. In this group the five-year arrest rate was 52
      per cent.

PMID- 15434714
TI  - Hematologic features which may influence Rh immunization.
AB  - The biologic features which may influence Rh sensitization in the mother and
      hemolytic disease in the newborn are conditioned by the hereditary immunologic
      pattern of the subjects, the antigenic characteristic of the blood group specific
      substances, the character of the antibody responses, the inherent susceptibility
      to disease as a result of the immune mechanism, and the character and sequence of
      exposure to the antigenic substance. In respect to Rh-negative women, there
      appears to be a greater vulnerability to immunization among those of blood group
      A. In regard to the infant, the compatibility of the maternal-infant blood types
      and the part they play in the phenomenon of the competition of antigens may
      influence the occurrence of hemolytic disease in the newborn.

PMID- 15434715
TI  - Precancerous dermatoses.

PMID- 15434716
TI  - Cancer of the skin.

PMID- 15434717
TI  - Other malignant conditions involving the skin.

PMID- 15434718
TI  - Chronic relapsing Q fever: treatment with streptomycin aureomycin, and
      chloramphenicol.

PMID- 15434719
TI  - Progressive muscular dystrophy associated with retinitis pigmentosa.

PMID- 15434720
TI  - The University of California program in cancer research.

PMID- 15434721
TI  - The objectives and applications of meat inspection.

PMID- 15434722
TI  - External diseases and injuries of the eye.

PMID- 15434723
TI  - On the chemotherapy of caecal coccidiosis (Eimeria tenella) of chickens; the use
      of a standardized test to determine coccidiostatic properties of drugs.

PMID- 15434724
TI  - Malignant uterine tumour in a cow.

PMID- 15434725
TI  - The Canadian Public Health Association; an appreciation.

PMID- 15434726
TI  - Incidence of cancer in Saskatchewan in 1948.

PMID- 15434727
TI  - A survey of cancer in Middlesex County, Ontario.

PMID- 15434728
TI  - Serum phosphatase values of school children.

PMID- 15434729
TI  - The pollution problem in Ontario.

PMID- 15434730
TI  - Bacteriophages for C. diphtheriae.

PMID- 15434731
TI  - CANADIAN Public Health Association, 1949-1950; report of the Committee on
      Professional Education.

PMID- 15434732
TI  - FINAL report of the National committee for School Health Research sponsored by
      the Canadian Education Association and the Canadian Public Health Association; a
      five-year program in school health research.

PMID- 15434733
TI  - REPORT of the Canadian Committee on Chemical Water Standards.

PMID- 15434734
TI  - Exfoliative cytological diagnosis.

PMID- 15434735
TI  - Physiological factors of significance in paediatric anesthesia.

PMID- 15434736
TI  - Primary or idiopathic pleurisy with effusion.

PMID- 15434737
TI  - Needle biopsy of the liver.

PMID- 15434738
TI  - Rheumatoid arthritis: results of treatment with desoxycorticosterone acetate and
      ascorbic acid (arthrodox).

PMID- 15434739
TI  - Flaxedil, a new curarizing agent.

PMID- 15434740
TI  - Convulsions and hemiplegia in pertussis prophylaxis.

PMID- 15434741
TI  - Friedlander's bacillus meningitis.

PMID- 15434742
TI  - Early symptomatology of carcinoma of the lung.

PMID- 15434743
TI  - Neurological complications of infectious mononucleosis.

PMID- 15434744
TI  - Pulmonary calcification and histoplasmin sensitivity.

PMID- 15434745
TI  - Failures after operations for procidentia uteri.

PMID- 15434747
TI  - Adrenal neuroblastoma.

PMID- 15434746
TI  - Giant follicular hyperplasia of the rectum showing malignant degeneration.

PMID- 15434748
TI  - Multiple myeloma.

PMID- 15434749
TI  - A hyperglycaemic and glycogenolytic factor of the pancreas.

PMID- 15434750
TI  - Esophagogastrostomy in the treatment of cardiospasm.

PMID- 15434751
TI  - Spontaneous rupture of the normal spleen during labour.

PMID- 15434752
TI  - Leuco-erythroblastic anemia.

PMID- 15434753
TI  - Spontaneous rupture of intrathoracic gastric pouch.

PMID- 15434754
TI  - Australia's flying doctors.

PMID- 15434755
TI  - Mottled enamel in Alberta.

PMID- 15434756
TI  - Some observations on genius.

PMID- 15434757
TI  - Excessive x-ray exposure.

PMID- 15434758
TI  - Newer concepts of the etiology and management of idiopathic ulcerative colitis.

PMID- 15434759
TI  - Homosexuality--a mental hygiene problem.

PMID- 15434760
TI  - The treatment of acutely intoxicated alcoholics.

PMID- 15434761
TI  - Oral penicillin prophylaxis in rheumatic fever patients.

PMID- 15434762
TI  - Medical aspects of bone disease with particular reference to osteoporosis.

PMID- 15434763
TI  - The management of obesity.

PMID- 15434764
TI  - The treatment of syphilis.

PMID- 15434765
TI  - Amaurosis in whooping cough.

PMID- 15434766
TI  - Antihistaminic drugs.

PMID- 15434768
TI  - Fractures of the malar bone and zygomatic arch.

PMID- 15434767
TI  - Neurotoxicity of dihydrostreptomycin.

PMID- 15434769
TI  - A new sedative combination for general practice.

PMID- 15434770
TI  - Acute leukaemia with a folic acid antagonist.

PMID- 15434771
TI  - Eclampsia treated with cortisone.

PMID- 15434772
TI  - Cutaneous leishmaniasis; oriental sore.

PMID- 15434773
TI  - Megaloblastic anaemia of pregnancy, refractory to liver therapy, but responding
      to folic acid.

PMID- 15434774
TI  - Perforation of small intestine by a fragment of celery.

PMID- 15434775
TI  - Uncontrollable hives; treated by a synthetic adrenal-cortex compound.

PMID- 15434776
TI  - Transection of the bowel at the duodenal-jejunal junction.

PMID- 15434777
TI  - Is Canada healthy?

PMID- 15434778
TI  - Camphorated oil asphyxia.

PMID- 15434780
TI  - Nursing on Canada's rooftop.

PMID- 15434779
TI  - CANADIAN Nurses' Association at University of British Columbia.

PMID- 15434781
TI  - A health survey in the far north.

PMID- 15434782
TI  - Highlights of treaty at Oxford House.

PMID- 15434783
TI  - The nurse and the law.

PMID- 15434784
TI  - Aims of professional education.

PMID- 15434785
TI  - Developing the social and health aspects of nursing.

PMID- 15434786
TI  - Hidden diabetes with psychosis.

PMID- 15434787
TI  - The value of visual aids.

PMID- 15434788
TI  - [Aides in the nursing team].

PMID- 15434789
TI  - Learning by seeing.

PMID- 15434790
TI  - The immediate task.

PMID- 15434791
TI  - The trumpet in the dust.

PMID- 15434792
TI  - The International Council of Nurses: a world force in nursing.

PMID- 15434793
TI  - Closing the gap in the tuberculosis program.

PMID- 15434794
TI  - [Group social service].

PMID- 15434795
TI  - The new look in typhoid fever.

PMID- 15434796
TI  - Chloromycetin therapy.

PMID- 15434797
TI  - Impressions of a new graduate.

PMID- 15434798
TI  - Nurses and nutrition.

PMID- 15434799
TI  - A student affiliates with the Victorian Order of Nurses.

PMID- 15434800
TI  - Recent studies on corneal metabolism and growth: a review.

PMID- 15434801
TI  - Studies in Hodgkin's syndrome. XI The influence of normal serum and Hodgkin's
      serum on cellular growth and morphology in tissue culture.

PMID- 15434802
TI  - The virus-induced rabbit papilloma-to-carcinoma sequence. Immunological tests for
      papilloma virus in cottontail carcinomas.

PMID- 15434803
TI  - The significance of the anterior chamber in tumor transplantation. I.
      Transplantation of mouse neuroblastoma C1300 to homologous hosts.

PMID- 15434804
TI  - Studies on xanthine oxidase during carcinogenesis by p-dimethylaminoazobenzene.

PMID- 15434805
TI  - Application of the Seibert tryptophane-acid reaction to the serum of malignancy.

PMID- 15434806
TI  - Catalase studies on normal and cancerous rats.

PMID- 15434807
TI  - Some studies of the excretion of diazotizable material after feeding 2
      acetylaminofluorene to rats.

PMID- 15434808
TI  - Inhibition of nucleic acid synthesis by folic acid antagonists.

PMID- 15434809
TI  - Relative susceptibility of various organs to tumor transplantation.

PMID- 15434810
TI  - Titration of the milk agent virus in milk and lactating mammary gland cells.

PMID- 15434811
TI  - [Bruno Krisch on his 60th birthday].

PMID- 15434812
TI  - [The individual heart].

PMID- 15434813
TI  - The duration of the ventricular systole.

PMID- 15434814
TI  - Electrocardiographic observations on the mechanism of the electrical alternans of
      the heart.

PMID- 15434815
TI  - Heart contusion in coronary disease.

PMID- 15434816
TI  - Congenital dextrocardia with situs inversus complicated by hypertension and
      angina pectoris.

PMID- 15434817
TI  - Early observations on the mechanism of auricular fibrillation.

PMID- 15434818
TI  - Influence of castration on blood pressure.

PMID- 15434819
TI  - Cardiac effects of N-alkyl homologues of epinephrine (N-isopropyl- and N-ethyl
      epinephrine).

PMID- 15434820
TI  - Intravenous procaine; its effect on the human electrocardiogram and on cardiac
      arrhythmias.

PMID- 15434821
TI  - Recent studies on baro- and chemoreceptor function.

PMID- 15434822
TI  - [Experimental Wenckebach periods].

PMID- 15434823
TI  - [Comparative physiology of the embryonic and fully-developed heart].

PMID- 15434824
TI  - [Preparation of samples for the determination of iron by sulfosalicylic acid].

PMID- 15434825
TI  - [Pharmaceutic microbiology].

PMID- 15434826
TI  - [New penal laws].

PMID- 15434827
TI  - [Not Available].

PMID- 15434828
TI  - [New drugs].

PMID- 15434829
TI  - [Isolation of influenza virus in Czechoslovakia].

PMID- 15434830
TI  - [Experimental immunization against hog paralysis with adsorbate and
      krystallviolet vaccine].

PMID- 15434831
TI  - [Syngamus infection in pheasants (Phasianus colchicus L.) during hunting season].

PMID- 15434832
TI  - [Control of ticks].

PMID- 15434833
TI  - [Parotitis in animal and man].

PMID- 15434834
TI  - [Fluorine content in water in Czechoslovakia and its significance in public
      health].

PMID- 15434835
TI  - [Problem of the diagnosis of chronic alcoholism].

PMID- 15434836
TI  - [Staphylococcic enterotoxicosis].

PMID- 15434837
TI  - [Arytenoidectomy in the treatment of paralysis of the recurrent laryngeal nerve].

PMID- 15434838
TI  - [Chlorethylamine therapy; treatment of bronchogenous carcinoma].

PMID- 15434839
TI  - [Clinical and central roentgenographic service].

PMID- 15434840
TI  - [Remarks on the treatment of erythematodes].

PMID- 15434841
TI  - [Flavoderma following use of the hand cream].

PMID- 15434842
TI  - [Determination of gamma-globulin in serum by the method of Verhagen's technic of
      calcium-formolgel reaction].

PMID- 15434843
TI  - [Acrodermatitis chronica atrophicans (Herxheimer-Pick) and anetodermia
      (Jadassohn) treated with penicillin].

PMID- 15434844
TI  - [The influence of the retardation substances on the penicillin levels].

PMID- 15434845
TI  - [Determination of penicillin in blood].

PMID- 15434846
TI  - [The skin and the diencephalon].

PMID- 15434848
TI  - [Treatment or erythematodes].

PMID- 15434847
TI  - [Experimental study of sublimate patch tests and the effect of antihistaminic
      drugs on the epidermoreaction].

PMID- 15434849
TI  - [Histologic changes caused by electric current].

PMID- 15434850
TI  - [Effect of retardation substances on penicillin levels].

PMID- 15434851
TI  - [An unusual form of elephantiasis].

PMID- 15434852
TI  - [Experimental study of sublimate patch tests and the effect of antihistaminic
      drugs on the epidermoreaction].

PMID- 15434854
TI  - [Nutrition in pregnancy].

PMID- 15434853
TI  - [Jiri Trapl; 70th anniversary].

PMID- 15434855
TI  - [Kymographic insufflation in the diagnosis of tubal sterility].

PMID- 15434856
TI  - [Classification of vaginal discharges in children].

PMID- 15434857
TI  - [Statistical data on incidence of premature birth and mortality in Prague, 1947
      1948].

PMID- 15434858
TI  - [Effect of acetylcholine, adrenaline and histamine on the human uterus in vitro].

PMID- 15434859
TI  - [Ovarian seminoma in a girl 13 years of age].

PMID- 15434860
TI  - [Diagnosis and treatment of adnexitis].

PMID- 15434861
TI  - [Studies of the serum proteins fraction in pregnancy].

PMID- 15434862
TI  - [Modifications of the refractometric values of the serum proteins in pregnancy].

PMID- 15434863
TI  - [Differential diagnosis of the blood sedimentation rate in pregnancy].

PMID- 15434864
TI  - [Prevention of fetal erythroblastosis in pregnancy].

PMID- 15434865
TI  - [Indications for cesarean section].

PMID- 15434866
TI  - [Narcamon anesthesia in gynecological operations of short duration].

PMID- 15434867
TI  - [Case of habitual abortion treated successfully with agostilben].

PMID- 15434868
TI  - [Effect of agostilben ointment on puerperal mastitis].

PMID- 15434869
TI  - [Prevention and therapy of cracked nipples].

PMID- 15434870
TI  - [Management of the first stage of labor and use of papaverin-belladonna
      amidopyrine drug combination].

PMID- 15434871
TI  - [Indications and dosage of uterine stimulants in the fourth stage of labor].

PMID- 15434874
TI  - [Revue of the activities of the III Obstetric and Gynecologic Clinic, 1949].

PMID- 15434873
TI  - [Recto-cervical fistula diagnosed by x-rays].

PMID- 15434872
TI  - [Indications and dosage of ergot extracts in puerperium].

PMID- 15434876
TI  - Illness experience of a group of normal children.

PMID- 15434875
TI  - Children's ethnic attitudes: I. relationship to certain personality factors.

PMID- 15434877
TI  - An acoustical comparison of vocal pitch in seven- and eight-year-old children.

PMID- 15434878
TI  - The reliability and validity of the Mummery ascendance score for five-year-old
      children.

PMID- 15434879
TI  - Nei Ching, the Chinese canon of medicine.

PMID- 15434880
TI  - The doctor in Chinese drama.

PMID- 15434881
TI  - A short history of psychiatry and mental hygiene in China.

PMID- 15434882
TI  - Life of Yeh Kuei with an actograph.

PMID- 15434884
TI  - Congenital cystic disease of the lung.

PMID- 15434883
TI  - Salmonella blegdam infection in the Far East, with especial reference to the
      thirteen cases seen in Shanghai.

PMID- 15434885
TI  - Paralysis of extraocular muscles following spinal anesthesia; report of 2 case.

PMID- 15434886
TI  - Complications after tracheotomy.

PMID- 15434887
TI  - Chronic intussusception in children; a report of 2 cases.

PMID- 15434888
TI  - Treatment of papilloma and verruca with oil of Brucea javanica.

PMID- 15434889
TI  - An experiment with oil of Brucea javanica in the treatment of papilloma of the
      external auditory canal.

PMID- 15434890
TI  - The Waterhouse-Friderichsen syndrome; report of a case.

PMID- 15434891
TI  - Acute complete inversion of uterus; with a report of 2 cases.

PMID- 15434892
TI  - Choledochus cyst; report of a case.

PMID- 15434893
TI  - Recent studies on the experimental production of rheumatic fever in animals; a
      review.

PMID- 15434894
TI  - [Relief of pain by resection of the presacral nerve].

PMID- 15434895
TI  - [So-called primary inflammatory stenosis of the hepatic duct, and its etiology].

PMID- 15434896
TI  - [Treatment indicated in so-called cardiospasm].

PMID- 15434897
TI  - [Treatment of furuncle of the face].

PMID- 15434898
TI  - [Mechanism of ultrasonic therapy, with special reference to ischialgia and
      neuralgia].

PMID- 15434899
TI  - [Treatment of neglected dislocation of the distal radioulnar joint].

PMID- 15434900
TI  - [New method of surgical therapy in Winiwarter-Burger disease of the brain].

PMID- 15434901
TI  - [Bancroft-Plenk technic of resection in cases of difficult or inoperable duodenal
      ulcer].

PMID- 15434902
TI  - [On neurovascular surgery in treatment of gastric ulcer].

PMID- 15434903
TI  - [Technic of extradural spinal remisection].

PMID- 15434904
TI  - [Surgery in wrist drop, with reference to physical laws].

PMID- 15434905
TI  - [Treatment of intestinal prolapse in patients with artificial anus].

PMID- 15434906
TI  - [Treatment of surgical tuberculosis].

PMID- 15434907
TI  - [Genesis of deep peptic ulcer].

PMID- 15434908
TI  - [Successful therapy of metastasizing actinomycosis].

PMID- 15434909
TI  - [Extensive retroperitoneal hematoma following diagnostic anesthesia of the lumbar
      sympathetic nerve].

PMID- 15434910
TI  - [Xanthofibroma of the stomach].

PMID- 15434911
TI  - [Fibroma of the radix mesenterii].

PMID- 15434912
TI  - [Pneumatosis cystoides intestinalis in a case of stenotic peptic ulcer].

PMID- 15434913
TI  - [Mesenteric lacunas or mesenteric rents?].

PMID- 15434914
TI  - [Pseudoappendicitis in carcinoma of the cecum].

PMID- 15434915
TI  - [Procedures in university teaching].

PMID- 15434916
TI  - [Problem of the origin of man].

PMID- 15434917
TI  - [Magma and the formation of igneous rocks].

PMID- 15434918
TI  - [Nucleoprotein content of cellular nuclei].

PMID- 15434919
TI  - [Unusual meteorological situation in the Argentine Republic from 7-15 May 1950].

PMID- 15434920
TI  - [Identification of lepra explosiva of the orange with leprosis of citrus fruits].

PMID- 15434921
TI  - [Miguel Fernandez (1882-1950)].

PMID- 15434923
TI  - [The problem of the origin of man].

PMID- 15434922
TI  - [Book collection of General San Martin].

PMID- 15434925
TI  - [Recent progress in photosynthesis in plants].

PMID- 15434924
TI  - [Agricultural soil in the planning of Argentine natural resources].

PMID- 15434926
TI  - [Anti-reflecting laminae].

PMID- 15434927
TI  - [A new fossil species of Nothofagoxylon from Neuquen, Argentina].

PMID- 15434928
TI  - [Natural selection of the gametophyte of corn].

PMID- 15434929
TI  - [Simple demonstration of the Gauss formula which explains its great generality].

PMID- 15434930
TI  - [Substitute for celloidin for histological inclusions].

PMID- 15434931
TI  - [Jose Wurschmidt, 1886-1950].

PMID- 15434932
TI  - The psychology of obesity.

PMID- 15434933
TI  - The electrical conductivity of living tissues as it pertains to
      electrocardiography. I. Review of the problem of homogeneity vs. non-homogeneity,
      an outline of the technical aspects of tissue resistivity measurements, and a
      critical and experimental analysis of certain pertinent experiments.

PMID- 15434934
TI  - Localized interlobar effusion in congestive heart failure; vanishing tumor of the
      lung.

PMID- 15434935
TI  - Effect of khellin on coronary artery insufficiency as evaluated by
      electrocardiographic tests.

PMID- 15434936
TI  - Some characteristics of certain reflexes which modify the circulation in man.

PMID- 15434937
TI  - The isolation of hypertensin from the circulating blood of dogs by dialysis in an
      artificial kidney.

PMID- 15434938
TI  - The relationship between prothrombin time and bleeding in the clinical use of
      dicumarol after operation.

PMID- 15434939
TI  - The effect of the dependent position upon blood flow in the limbs.

PMID- 15434940
TI  - Cholesterol, cholesterol esters and phospholipids in health and in coronary
      artery disease; morphology and serum lipids in man.

PMID- 15434941
TI  - Circulatory dynamics in spontaneous and nephrogenic hypertensive dogs during the
      depressor response to acute inflammation.

PMID- 15434942
TI  - The effect of exercise on the plasma volume of patients with heart failure.

PMID- 15434943
TI  - Antidiuretic action of the urine of patients in cardiac failure.

PMID- 15434944
TI  - Arterioles of kidney and pancreas in cases of cardiac hypertrophy of undetermined
      causation.

PMID- 15434945
TI  - Intrabronchial electrocardiography.

PMID- 15434946
TI  - Paroxysmal ventricular tachycardia with second degree V-A block and reciprocal
      rhythm.

PMID- 15434947
TI  - Transfixion of the heart by embedded ice pick blade with eight months' survival.

PMID- 15434948
TI  - Coronary embolism; review of the literature and report of a unique case.

PMID- 15434949
TI  - Atypical secondary or symptomatic thrombocytopenic purpura developing with the
      use of quinidine sulfate.

PMID- 15434950
TI  - Primary systemic amyloidosis mimicking chronic constrictive pericardial disease.

PMID- 15434951
TI  - [Clinical note on medical rhigosis and thalposis].

PMID- 15434952
TI  - [Pathogenesis of edema, water metabolism and pre-edema].

PMID- 15434953
TI  - [Hematic regulation in hypophysectomized animals. V. Hematic reaction to
      trepanation and ventricular injection of air].

PMID- 15434954
TI  - [Study of a concrete case of artificial insemination; the child of a cadaver from
      the legal point of view and the codes].

PMID- 15434955
TI  - [Amyotrophic lateral sclerosis syndrome due to hernia of cervical intervertebral
      disk].

PMID- 15434956
TI  - [Tuberculous adenomyositis].

PMID- 15434957
TI  - Infectious mononucleosis in childhood; a survey of 34 cases; special report.

PMID- 15434958
TI  - Refractory megaloblastic anemia.

PMID- 15434959
TI  - A case of acute phosphorus poisoning with recovery.

PMID- 15434960
TI  - Adrenal insufficiency in infancy.

PMID- 15434961
TI  - CLINICO-pathological conference; hemiplegia of sudden onset with subsequent
      clearing; generalized convulsions; coma and presence of fever.

PMID- 15434962
TI  - Treatment of leukemia in children with folic acid antagonists.

PMID- 15434963
TI  - A suggested classification of jaundice in infants and children.

PMID- 15434964
TI  - Subdiaphragmatic abscess in children.

PMID- 15434965
TI  - Congenital rhabdomyoma of the heart.

PMID- 15434966
TI  - CLINICO-pathological conference; diffuse nodular cirrhosis and subacute
      hepatitis; icterus; cerebral edema and probable prothrombin deficiency.

PMID- 15434967
TI  - [Experimental lesions in the rat caused by talc].

PMID- 15434968
TI  - [Virucidal effects of aureomycin].

PMID- 15434969
TI  - [Synergy of chloromycetin and aureomycin in the treatment of the typhus infection
      in the mouse].

PMID- 15434970
TI  - [Tetany with alkalosis and increase of serum potassium without hypocalcemia].

PMID- 15434971
TI  - [Biochemistry of ossification. Phosphorylation and calcification].

PMID- 15434972
TI  - [Identity of pterine pigment with blue fluorescence of Bombyx mori and
      fluorescyanine].

PMID- 15434973
TI  - [Experimental allergic encephalomyelitis].

PMID- 15434974
TI  - [Application of the isostere theory in the series of spasmolytics (derivatives of
      cyclohexylcyclohexanecarboxylic acid].

PMID- 15434975
TI  - [In vitro resistance of staphylococci to penicillin].

PMID- 15434977
TI  - [Electric complex of the heart, sum of negatives of right and left ventricles].

PMID- 15434976
TI  - [Additional data relative to sero-diagnosis of tularemia].

PMID- 15434978
TI  - [Left ventricle, site of the elevation of the terminal deflection (wave length T)
      during total anemia of the heart].

PMID- 15434979
TI  - [Latent infection of a newborn guinea pig of a brucellosis infected mother (Br.
      melitensis)].

PMID- 15434980
TI  - [Variation in globular values during experimental erythremia; hypothesis of
      hemoglobin redistribution].

PMID- 15434981
TI  - [Effect of diethylstilbestrol on cupremia].

PMID- 15434982
TI  - [Dihydroxycodeinone activator of procainesterase].

PMID- 15434983
TI  - [Pseudocholinesterase and dihydroxycodeinone].

PMID- 15434984
TI  - [Study of capillary permeability. Effect of bacterial autolysates and various
      toxins].

PMID- 15434985
TI  - [Increase of the capillary permeability in the inflammation centers].

PMID- 15434986
TI  - [Hemodipsus lyriocephalus Burmeister, Ixodes ricinus Linne, ectoparasites of
      hares, possible vectors of tularemia in France].

PMID- 15434987
TI  - [Anaculture vaccination of the guinea pig against Brucella melitensis].

PMID- 15434988
TI  - [Contraction of a striated muscle stimulated in situ].

PMID- 15434989
TI  - [Experimental lesion in the rat caused by urethane].

PMID- 15434990
TI  - [Mechanism of action of antithyroid drugs: inhibition of the peripheral effect of
      thyroxin].

PMID- 15434991
TI  - [Local antihistaminic effect of N-dimethylamino-2-propyl-1-thiodiphenylamine
      (3277 R.P.) injected intraarterially].

PMID- 15434992
TI  - [Influence of pH on the inhibition of muscular phosphorylase in the rat by
      chloropicrine].

PMID- 15434993
TI  - [Age and speed of healing of experimental wounds in a rat].

PMID- 15434994
TI  - [Application of the sulfophospho-vanillic reaction in study of the phospho-lipids
      in the serum of subjects with jaundice].

PMID- 15434995
TI  - [Mechanism of the appearance of nervous symptoms in a mouse infected by
      Mycobacterium tuberculosis strain 607].

PMID- 15434996
TI  - [Seasonal variations of the composition of the blood in the dog. Role of the
      supra-optico postpituitary system].

PMID- 15434997
TI  - [Comparison of the effects of estradiol and dimethyl-ethyl-allenolic acid].

PMID- 15434998
TI  - [Adrenochrome and in vitro oxidation of L-ascorbic acid].

PMID- 15434999
TI  - [Mechanism of the action of vitamin C2 (vitamin P) on the thyroid].

PMID- 15435000
TI  - [Decrease of a peptone shock in the dog by combined action of atropine and a
      histamine antagonist].

PMID- 15435001
TI  - [Identical effect of the sympathomimetic factor of genista and adrenalin on
      capillary permeability and on audiogenic crisis].

PMID- 15435002
TI  - [Preservation of the emetic power of apomorphine injected subcutaneously in the
      presence of yohimbine].

PMID- 15435003
TI  - [Effect of splenectomy on the evolution and relapse of Plasmodium berghei Vincke
      and Lips infection in the white rat].

PMID- 15435004
TI  - [Photolysis of the transitory visual yellow of the retina].

PMID- 15435005
TI  - [Progestational and accessory gestative bodies in the human ovary].

PMID- 15435006
TI  - [Diagram of the total innervation of a striated muscle. (Malleus muscle of the
      guinea pig)].

PMID- 15435007
TI  - [Mechanism of action of lipid substances in the phenomenon of specific
      precipitation. Action of ninhydrin].

PMID- 15435008
TI  - [Autografts of the placenta in the rat].

PMID- 15435009
TI  - [Symelic larvae obtained by transverse section of the germ of Leptinotarsa].

PMID- 15435010
TI  - [Greater frequency of hypertension caused by perinephritis or
      desoxycorticosterone in the diabetic rat].

PMID- 15435011
TI  - [Increase of blood volume and extracellular fluid in the diabetic and
      hypertensive rat].

PMID- 15435012
TI  - [Histological modifications of the testicle of the toad following
      hypophysectomy].

PMID- 15435013
TI  - [Local effect of estradiol implanted in the pancreas on the islands of
      Langerhans].

PMID- 15435014
TI  - [Glycogen content of leukocytes in human and experimental diabetes].

PMID- 15435015
TI  - [Effect of ovarian graft on the evolution of diabetes in the castrated female
      rat].

PMID- 15435016
TI  - [Alkaline phosphatase of the rat kidney with pancreatic diabetes].

PMID- 15435017
TI  - [Streptococcic antigen and bacteriolysis by actinomyces].

PMID- 15435018
TI  - [Action of ethyl-4-ethane sulfonylpiperazine on the shock of animals following
      burns].

PMID- 15435019
TI  - [Poisson's series of distribution of total streptomycin resistance in normal
      staphylococci strains].

PMID- 15435020
TI  - [Distribution of productive strains of colicine V in normal and pathological
      feces].

PMID- 15435021
TI  - [Analogy between colicine E and K and bacteriophage II and III].

PMID- 15435022
TI  - [Distinctive characteristics of colicine E and K and of bacteriophages II and
      III].

PMID- 15435023
TI  - [A variant of Micrococcus lysodeikticus dependent on streptomycin].

PMID- 15435024
TI  - [Influence of implantation of diethylstilbestrol on the breast and the hypophysis
      of the white rate].

PMID- 15435025
TI  - [Influence of certain metallic ions on the survival of rats following a mortal
      dose of x-rays].

PMID- 15435026
TI  - [Influence of desoxycorticosterone, n-hexyl butyrate, alpha-naphthylthiourea, and
      gum arabic on the survival of rats following a mortal dose of x-rays].

PMID- 15435027
TI  - [Attempts of virus culture in the crown gall, tumors on plant species, not
      yielding generalized infection].

PMID- 15435028
TI  - [Negative action of cancerogenic products on plants].

PMID- 15435029
TI  - [Excess of lipids in the liver and biliary ducts in chronic alpha
      hexachlorocyclohexane poisoning in the dog].

PMID- 15435030
TI  - [Action of ultrasonics on the MM strain of poliomyelitis in the mouse].

PMID- 15435031
TI  - [Fatty degeneration of the muscular tissue in chronic gamma hexachlorocyclohexane
      poisoning in the dog].

PMID- 15435032
TI  - [Action of x-rays on the membrane of red blood cells].

PMID- 15435033
TI  - [Variations of the resistance of blood coagulum].

PMID- 15435034
TI  - [Reflex conditioned by imagination in the encephalogram].

PMID- 15435035
TI  - [Presentation of radiographs of Dr. Baud relative to pelvic phlebography].

PMID- 15435036
TI  - [Three cases of ligation of the inferior vena cava for embolizing phlebitis in
      gynecological patients].

PMID- 15435037
TI  - [Phlebitis in gynecology].

PMID- 15435038
TI  - [Anticoagulant medication, preventive and curative, in gynecological surgery].

PMID- 15435039
TI  - [Preventive and curative ambulatory treatment of phlebitis particularly in
      obstetrics and gynecology].

PMID- 15435040
TI  - [Colpodystrophy of lactation].

PMID- 15435041
TI  - [Treatment of rheumatic affections by Lewin and Wassen method].

PMID- 15435042
TI  - [Procedures in ovarian function tests].

PMID- 15435043
TI  - [The psychic components of pain in rheumatic diseases].

PMID- 15435044
TI  - [Ambulatory treatment of genu valgum in children].

PMID- 15435045
TI  - [In favor of rural medicine].

PMID- 15435046
TI  - [Cicatrization of wounds].

PMID- 15435047
TI  - [Cirrhosis of the liver and meat deficiency].

PMID- 15435048
TI  - [Evaluation of hematological examinations].

PMID- 15435049
TI  - [Nickel in therapeutic use].

PMID- 15435050
TI  - [Nervous infantile anorexia; mother and child].

PMID- 15435051
TI  - [Prescriptions of narcotics].

PMID- 15435052
TI  - [Parotid lithiasis].

PMID- 15435053
TI  - [Precipitant urination].

PMID- 15435054
TI  - [Breakdown and reclassification of poliomyelitis].

PMID- 15435055
TI  - [Personal experience with hormonotherapy in cancer].

PMID- 15435056
TI  - [Secondary treatment of cutaneous grafts].

PMID- 15435057
TI  - Blue Cross protects the people; who protects Blue Cross?

PMID- 15435058
TI  - The need for standardization of breast cancer records.

PMID- 15435059
TI  - Unsuspected foreign body of bronchus; case report.

PMID- 15435060
TI  - The clinical value of electrocardiography.

PMID- 15435061
TI  - Lipectomy for abdominal fat.

PMID- 15435062
TI  - Retrocaval ureter; case report.

PMID- 15435063
TI  - Diabetics live long, but can live longer and more efficiently.

PMID- 15435064
TI  - Psychosomatic medicine and rehabilitation.

PMID- 15435065
TI  - General practice in Litchfield County; an abstract of a thesis by Archie J.
      Golden, M.D.

PMID- 15435066
TI  - Subtotal gastrectomy for peptic ulcer and antral gastritis; end results in 92
      cases subjected to operation between 1942 and 1947.

PMID- 15435067
TI  - Hypofunction of the adrenal glands in newborn infants.

PMID- 15435068
TI  - Appendectomy with recovery in a hemophiliac; a case report.

PMID- 15435070
TI  - Doctors, patients and litigants.

PMID- 15435069
TI  - Unilateral infiltrative cellular ependymoblastoma; a case report.

PMID- 15435071
TI  - Practical aspects of the differential diagnosis of jaundice.

PMID- 15435072
TI  - [Clinico electrocardiographic considerations on two cases of heart wounds].

PMID- 15435073
TI  - [Considerations of the pathogenetic plurality of sino-auricular block].

PMID- 15435074
TI  - [Clinical and electrocardiographic considerations of 50 cases of bundle branch
      block].

PMID- 15435075
TI  - New state facilities for criminally inclined psychopaths in Delaware.

PMID- 15435076
TI  - Dynamic concepts in psychiatry.

PMID- 15435077
TI  - The diagnosis and treatment of epilepsy.

PMID- 15435078
TI  - The effects of early and late diagnosis on the results after brain tumor surgery.

PMID- 15435080
TI  - Delaware and its health center.

PMID- 15435079
TI  - Personality, physique and disease.

PMID- 15435081
TI  - Clinical evaluations of psychopathic personalities.

PMID- 15435082
TI  - A mental hygiene clinic goes to the schools.

PMID- 15435083
TI  - Mental factors in general medicine and surgery.

PMID- 15435084
TI  - Emotional catharsis, a psychotherapeutic method for the general practitioner.

PMID- 15435085
TI  - Child guidance at Governor Bacon Health Center: the Seizure Control Unit.

PMID- 15435086
TI  - Psychoses in the Negro; a preliminary study.

PMID- 15435087
TI  - The rationale for inpatient treatment of emotionally disturbed children.

PMID- 15435088
TI  - Pediatric activities at the Governor Bacon Health Center.

PMID- 15435089
TI  - Bilateral prefrontal lobotomy; a case report.

PMID- 15435090
TI  - Insulin therapy: an evaluation of 47 cases.

PMID- 15435091
TI  - The concept of the psychopathic personality.

PMID- 15435092
TI  - Personality problems of juvenile delinquents as revealed in psychological tests.

PMID- 15435093
TI  - The psychology department of the Governor Bacon Health Center.

PMID- 15435094
TI  - Parents come to the mental hygiene clinic.

PMID- 15435095
TI  - The parent's role at the Governor Bacon Health Center.

PMID- 15435096
TI  - Therapy with a child from a broken home: a case study.

PMID- 15435097
TI  - Psychotherapy with an aggressive adolescent girl: a case study.

PMID- 15435098
TI  - A psycho-somatic study into the nature, prevention and treatment of thumb-sucking
      and its relationship to dental deformity.

PMID- 15435099
TI  - Tumour of the soft palate; case report.

PMID- 15435100
TI  - A psycho-somatic study into the nature, prevention and treatment of thumb-sucking
      and its relationship to dental deformity.

PMID- 15435101
TI  - Genetics and the teeth.

PMID- 15435102
TI  - Dental materials in 1949; review of British and American progress.

PMID- 15435103
TI  - [The frequency of certain skin diseases in war- and post-war times].

PMID- 15435104
TI  - [In memoriam Hermann Roeschmann].

PMID- 15435105
TI  - [Specific cutaneous manifestations in myeloblastic leukemia].

PMID- 15435106
TI  - [Severe dental dystrophy, especially of the enamel in a young man with
      epidermolysis bullosa hereditaria dystrophica].

PMID- 15435107
TI  - [Onychodystrophy in the same man, with scarring of the skin on the phalanges].

PMID- 15435108
TI  - [Xeroderma pigmentosum with carcinomatous growth under the left eye; infrared
      photograph].

PMID- 15435109
TI  - [Post-climacteric impetigo herpetiformis].

PMID- 15435110
TI  - [Tuberculosis cutis necrotica, of special interest due to typical scars and the
      involvement of eyelids and external ear].

PMID- 15435111
TI  - [Porokeratosis Mibelli on the palmar surface in a young girl].

PMID- 15435112
TI  - [Fox-Fordyce disease in a man, with involvement of the areola].

PMID- 15435113
TI  - [Microsporotic focus on lanuginous skin, clinically indifferentiable from
      trichophytosis].

PMID- 15435114
TI  - [Microsporotic focus on the scalp].

PMID- 15435115
TI  - [Circumscribed alopecia following furunculosis].

PMID- 15435116
TI  - [Electroendosmotic experiments with dabylene (dimethylaminoethyl benzohydryl
      ether)].

PMID- 15435117
TI  - [Atrophodermia vermiculata].

PMID- 15435118
TI  - [Use of the diffusion method in study of antibiotics].

PMID- 15435119
TI  - [Place of penicillin in the treatment of syphilis].

PMID- 15435120
TI  - [Salvarsan allergy (ninth-day erythema and agranulocytosis)].

PMID- 15435121
TI  - [Pathogenesis and treatment of dyshidrosis lamellosa sicca].

PMID- 15435122
TI  - [Recent results at home and abroad in dermato-venereologic therapy].

PMID- 15435123
TI  - [Experience with recent methods of dermatovenereologic therapy in Germany].

PMID- 15435124
TI  - [Manifestations of cutaneous tuberculosis].

PMID- 15435125
TI  - [Acquired hemolytic anemia in hepatitis].

PMID- 15435126
TI  - [A particular course of tuberculosis of the lymph nodes and of general
      tuberculosis in adults].

PMID- 15435127
TI  - [Poisoning by Amanita phalloides in man].

PMID- 15435128
TI  - [Angina pectoris].

PMID- 15435129
TI  - [Prophylaxis and therapy of specific empyema following pneumolysis].

PMID- 15435130
TI  - [Static scoliosis in children].

PMID- 15435131
TI  - [Unsuitable treatment of diseases of the ear, nose and throat].

PMID- 15435132
TI  - [Development of medicine in the USSR].

PMID- 15435133
TI  - [Development of surgical anesthesia].

PMID- 15435134
TI  - [Experimental studies of synthetic vehicles for salves and suppositories].

PMID- 15435135
TI  - [Pathologic fibrinogen content of blood plasma].

PMID- 15435136
TI  - [Unipolar electrocardiography and its simplification with Seifert and Falley's
      new appliance].

PMID- 15435137
TI  - [Medicinal therapy of convulsive nervous diseases].

PMID- 15435138
TI  - [Local penicillin therapy of acute infections of the hand].

PMID- 15435139
TI  - [A steady source of power for the electrocardiograph].

PMID- 15435140
TI  - [Constellation types in the proteinogram].

PMID- 15435142
TI  - [Favorable and unfavorable results in the treatment of open pulmonary
      tuberculosis in children].

PMID- 15435141
TI  - [Remarkable increase in the occurrence of acute glomerulonephritis].

PMID- 15435143
TI  - [Palpation of the epigastric region].

PMID- 15435144
TI  - [Treatment of circulatory disorders with Homburg's multisaccharid].

PMID- 15435145
TI  - [Why is there still congenital syphilis? A contribution to prenatal prophylaxis].

PMID- 15435146
TI  - [In memory of Robert Koch].

PMID- 15435147
TI  - [Etiology of cancer; virus-like elementary organisms in cancer].

PMID- 15435148
TI  - [Respiratory regulation and dyspnea].

PMID- 15435149
TI  - [Dangers of suboccipital puncture].

PMID- 15435150
TI  - [Treatment of parenchymous hemorrhages with styptan].

PMID- 15435151
TI  - [Can contact lenses replace spectacles?].

PMID- 15435152
TI  - [Question of disability certificates for diabetics].

PMID- 15435153
TI  - [Drug registration and trade names].

PMID- 15435154
TI  - [Paleophysiology; its nature, means, and ends].

PMID- 15435155
TI  - [In memoriam Franz Volhard].

PMID- 15435156
TI  - [Significance of neuropathology in contemporary medicine].

PMID- 15435157
TI  - [Practical value of the Vaughan test (leukopenic index) in the diagnosis of
      nutritional allergic dermatoses].

PMID- 15435158
TI  - [Roentgenotherapy of tuberculosis].

PMID- 15435159
TI  - [Experience with the new antisyphilitic, neo-arsoluin (formerly arsaminol)].

PMID- 15435160
TI  - [Practical experiences with plenosol, a mistletoe preparation, in the treatment
      of arthrosis and polyarthritis].

PMID- 15435161
TI  - [Significance of neuropathology in contemporary medicine].

PMID- 15435162
TI  - [Importance of blood calcium determination in clinical diagnosis].

PMID- 15435163
TI  - [Report on autopsies in enteritis necroticans conducted at the Berlin-Spandau
      Institute of Pathology].

PMID- 15435164
TI  - [Mass Rh surveys in pregnancy; report from the Leipzig Prenatal Clinic].

PMID- 15435165
TI  - [Basic principles of obtaining therapeutic results by way of the sympathetic
      nervous system].

PMID- 15435166
TI  - [Myocardial disease and working capacity].

PMID- 15435167
TI  - [Question of solar and lunar influences upon the menstrual cycle and upon the
      daily number of births].

PMID- 15435168
TI  - [Comparative study of Still's disease and Felty's syndrome based on a case of
      Still's disease with an atypical verrucous endocarditis of Libman-Sacks].

PMID- 15435169
TI  - [Late results of splenectomy].

PMID- 15435170
TI  - [Question of permanent immunity following an attack of typhus].

PMID- 15435171
TI  - [Results of ultrasonic therapy of rheumatic and degenerative arthritis;
      neuropathologic aspect].

PMID- 15435172
TI  - [Experiences with surgery in diabetes].

PMID- 15435173
TI  - [Experience with antabuse in the treatment of chronic alcoholics].

PMID- 15435174
TI  - [Balneology; retrospect and prospect].

PMID- 15435175
TI  - [Testosterone therapy of incurable cancer of the female genitalia].

PMID- 15435176
TI  - [Role of folic acid in hemopoiesis].

PMID- 15435177
TI  - [Bacteriochemical serodiagnosis of typhoid fever].

PMID- 15435178
TI  - [Bedermin therapy of ascariasis].

PMID- 15435179
TI  - [Myeloblastic leukemia].

PMID- 15435180
TI  - [Electrocardiographic diagnosis of right and left hypertrophy with so-called
      unipolar chest and limb leads].

PMID- 15435181
TI  - [Significance of mechanical factors in the origin of muscular rheumatic pain].

PMID- 15435182
TI  - [Examination of kidney function before prostatectomy].

PMID- 15435183
TI  - [Canicola fever in the Oldenburg-Holstein district].

PMID- 15435184
TI  - [Comparative study of the blood picture in hemochromatosis and simple cirrhosis
      of the liver].

PMID- 15435185
TI  - [Value of high voltage roentgen irradiation as a palliative in bronchial
      carcinoma].

PMID- 15435186
TI  - [A clinical picture resembling meningoencephalitis in TB 1 therapy].

PMID- 15435187
TI  - [Egressin, a new chemotherapeutic for oxyuriasis in man].

PMID- 15435188
TI  - [A derivative of diphenyloxyacetic acid for use as an antispasmodic].

PMID- 15435189
TI  - [Effect of intervention upon the autonomic nervous system in the light of the
      synallactic theory].

PMID- 15435190
TI  - [Clinical observations on an epidemic of field fever].

PMID- 15435191
TI  - [Etiology of high blood pressure in affections of the nervous system, with
      special reference to polyneuritis and poliomyelitis].

PMID- 15435192
TI  - [Relapse, reinfection and superinfection in syphilis, based on observations made
      in a counselling bureau for venereal disease].

PMID- 15435193
TI  - [Chronic inflammations and cysts of the maxillary sinuses of dental origin].

PMID- 15435194
TI  - [Report on a year's experience with PAS in treatment of tuberculosis].

PMID- 15435195
TI  - [Toxicity of streptomycin].

PMID- 15435196
TI  - [Colorimetric determination of thiosemicarbazones in the urine].

PMID- 15435197
TI  - [In memoriam Wilhelm von Drigalski].

PMID- 15435198
TI  - [Brief introduction to teratology].

PMID- 15435199
TI  - [Basic therapy of poliomyelitic paralysis in general practice].

PMID- 15435200
TI  - [Observations on orthopedic therapy of poliomyelitis].

PMID- 15435201
TI  - [Progress in the treatment of infantile croup].

PMID- 15435202
TI  - [Epidemiology of infantile diphtheria].

PMID- 15435203
TI  - [Diagnosis of cystic fibrosis of the pancreas].

PMID- 15435204
TI  - [Cushing's syndrome in tumors of the adrenal cortex].

PMID- 15435205
TI  - [Penniform roentgen aspect of the muscle in progressive muscular dystrophy].

PMID- 15435206
TI  - [Serum protein and sedimentation rate during streptomycin and p-aminosalicylic
      acid therapy of tuberculosis in children].

PMID- 15435207
TI  - [Penicillin therapy of pneumonia].

PMID- 15435208
TI  - [Treatment of tonsillar abscess].

PMID- 15435209
TI  - [Increasing the efficacy of vaccine therapy in whooping cough].

PMID- 15435210
TI  - [Observations on polamidon therapy].

PMID- 15435211
TI  - [Results of prolonged TB I therapy of progressive pulmonary tuberculosis].

PMID- 15435212
TI  - [Experimental cold agglutination in man].

PMID- 15435213
TI  - [Parenteral use of trypsin].

PMID- 15435214
TI  - [Determination of blood calcium].

PMID- 15435215
TI  - [Duration of vaccination induced immunity to diphtheria].

PMID- 15435216
TI  - [Reply to Leick's article on the frequency of oxyuriasis vermicularis].

PMID- 15435217
TI  - [Chemical relationships of certain steroids and their significance in
      metabolism].

PMID- 15435218
TI  - [Question of subsequent pregnancies following the birth of deformed and diseased
      children; observations on glycogenosis and congenital myatonia].

PMID- 15435219
TI  - [Homologous serum hepatitis as an independent clinical aspect].

PMID- 15435220
TI  - [Resorption in pulmonary cavities].

PMID- 15435221
TI  - [Pernicious anemia during the war and after].

PMID- 15435222
TI  - [Etiology of Sjogren's syndrome].

PMID- 15435223
TI  - [Educational reform in otorhinolaryngology].

PMID- 15435224
TI  - [Diagnosis and treatment of rheumatic fever (acute rheumatoid arthritis)].

PMID- 15435225
TI  - [Lavage of tuberculous and mixed empyema of the pleural cavity].

PMID- 15435226
TI  - [Therapeutic use of strychnine in treatment of cardiac diseases].

PMID- 15435227
TI  - [Additional data to a specific therapy of psychoses].

PMID- 15435228
TI  - [Internal treatment of diseases of the biliary tract].

PMID- 15435229
TI  - [Evaluation of the thymo turbidity test].

PMID- 15435230
TI  - [Anaphylaxis in blood donors produced by reflux of the donee's blood].

PMID- 15435231
TI  - [Definition of the concept of skeletal-muscle tonus].

PMID- 15435232
TI  - [Comments on preceding article].

PMID- 15435233
TI  - [Observations on the so-called wartime ulcer].

PMID- 15435234
TI  - [The problem of rheumatism treatment of chronic rheumatoid polyarthritis with
      adrenocortical and hypophyseal hormones].

PMID- 15435235
TI  - [Approximal amalgam fillings; roentgenologic investigation of projecting
      fillings; cause and prevention of filling defects].

PMID- 15435236
TI  - [Etiology of dental caries].

PMID- 15435237
TI  - [Wire sutures in fracture of the jaw].

PMID- 15435238
TI  - [Principles of iontophoresis prior to filling of the root canal].

PMID- 15435239
TI  - [New aspects of possible methods of anchoring adgingival free-end prostheses].

PMID- 15435240
TI  - [Multiple primary sarcomatosis of the maxillary region, or late metastasis of a
      hypernephroma].

PMID- 15435241
TI  - [Professor Dr. Bernhard Gottlieb].

PMID- 15435242
TI  - [Significance of focal infection in internal and nervous disease].

PMID- 15435243
TI  - [Antiseptic action of the new Albrecht root filling].

PMID- 15435244
TI  - [Principles and technic in amalgam filling of the root canal, with special
      reference to copper amalgam].

PMID- 15435245
TI  - [Radioactive root fillings].

PMID- 15435246
TI  - [Problem of vital amputation].

PMID- 15435247
TI  - [A new test for the control of focal infection].

PMID- 15435248
TI  - [Radical or conservative dentistry? The answer of American dentistry to the
      problem of root therapy and focal infection].

PMID- 15435249
TI  - [Practical notes on iontophoresis prior to filling of the root-canal].

PMID- 15435250
TI  - [Broadened applicability of the suctor].

PMID- 15435251
TI  - [Physiology and pathology of the peripheral regulation of the circulation].

PMID- 15435252
TI  - [Securing closure of the incision in surgery of the alveolar process, with
      special reference to the incision technic in antrotomy].

PMID- 15435253
TI  - [Nutritional physiology and pathology and their relation to dental caries].

PMID- 15435254
TI  - [Observations on the pathogenesis and treatment of prognathism].

PMID- 15435255
TI  - [Facings with platinum pins for anterior bridges].

PMID- 15435256
TI  - [Sectional anchorage of post crowns (patented process)].

PMID- 15435257
TI  - [Dental focal infection and extraction].

PMID- 15435258
TI  - [Manufacture of artificial eyes by the dentist with use of artificial resin].

PMID- 15435259
TI  - [Cerebral circulation and its significance for the cerebral tissue].

PMID- 15435260
TI  - [Evipan narcosynthesis of patients with cerebral injury].

PMID- 15435261
TI  - [Cerebrotraumatic syndrome and pretraumatic structure].

PMID- 15435262
TI  - [Electroshock therapy of organic disease of the brain].

PMID- 15435263
TI  - [Functional shift and ideational pattern].

PMID- 15435264
TI  - [Recent results in the analysis of perceptive and motor function].

PMID- 15435265
TI  - [The principle of ideational patterns in cerebral pathology].

PMID- 15435267
TI  - [Critical detail in sensory perception].

PMID- 15435266
TI  - [Degrees of functional shift in optic perception due to organic motor disorders].

PMID- 15435268
TI  - [Forms of degeneration in motor function].

PMID- 15435269
TI  - [Involution of disorders of sensory perception due to cortical injury].

PMID- 15435270
TI  - [Topical pathology of acute anterior poliomyelitis].

PMID- 15435271
TI  - [Upon entering the ninetieth year of life].

PMID- 15435272
TI  - [The problem of hydrocephalus in carbon monoxide poisoning].

PMID- 15435273
TI  - [Actinomycosis and its localization in the central nervous system; clinical
      aspects, bacteriology and pathologic anatomy].

PMID- 15435274
TI  - [Postencephalographic fever and "central" rises in temperature in general].

PMID- 15435275
TI  - [Hyperplastic malformation of the tuber cinereum with precocious puberty].

PMID- 15435276
TI  - [Local hyperplasia of the hypothalamus with precocious puberty].

PMID- 15435277
TI  - [The frontothalamic syndrome in Pick's disease].

PMID- 15435278
TI  - [Not Available].

PMID- 15435279
TI  - [Clinical observations on injury of the occipital lobes; problem of the
      interferential action of the right and left occipital lobes].

PMID- 15435280
TI  - [Diphenylhydantoin and vitamin C metabolism].

PMID- 15435281
TI  - [Clinical and pathologic aspects of the injurious effect of typhoid, paratyphoid,
      and cholera vaccination upon the nervous system].

PMID- 15435282
TI  - [Critical examination of the sequellae of non-perforating injuries of the brain,
      with special reference to encephalographic findings].

PMID- 15435283
TI  - [Von Falkenhausen and Gaida's insulin tolerance test of cerebral function].

PMID- 15435284
TI  - [Arthur Meiner on his 85th birthday].

PMID- 15435285
TI  - [Infrapapillary duodenal stenosis in an eleven year old boy].

PMID- 15435286
TI  - [Deficiency anemias of the postwar period].

PMID- 15435287
TI  - [Studies in iron metabolism; physiology of renal excretion of iron].

PMID- 15435288
TI  - [Pseudopolypus of the stomach].

PMID- 15435289
TI  - [Disorders of enzyme and acid production in the stomach; diagnosis and therapy].

PMID- 15435290
TI  - [Herbert Assmann].

PMID- 15435291
TI  - [Electrocardiographic diagnosis of right hypertrophy].

PMID- 15435292
TI  - [Manifestations of vasomotorautonomic insufficiency in inflammatory diseases of
      the peripheral nerves].

PMID- 15435293
TI  - [Favorable effect of peroral administration of p-aminobenzoic acid upon the
      culture of the pathogens of endocarditis lenta].

PMID- 15435294
TI  - [Normal zinc content in blood. serum and erythrocytes].

PMID- 15435295
TI  - [Determination and clinical significance of phosphatase activity in the blood].

PMID- 15435296
TI  - [Intestinal resorption of acetylene, a pharmacologic function test of portal
      circulation].

PMID- 15435297
TI  - [Respiration and constitution with special reference to the excursion gradient
      and respiratory index].

PMID- 15435298
TI  - [Pathogenesis of amyloidosis and symptomatology of amyloid contracted kidney].

PMID- 15435299
TI  - [Malignant erythroblastoma].

PMID- 15435300
TI  - [Toxoplasmosis in man].

PMID- 15435301
TI  - [The phagocytic megakaryocytes of the sternal punctate].

PMID- 15435302
TI  - [Effect of vegetable and lactovegetable diet upon nitrogen equilibrium and blood
      protein bodies].

PMID- 15435303
TI  - [Basal metabolism].

PMID- 15435304
TI  - [Determination of prothrombin as a liver function test].

PMID- 15435305
TI  - [A new method in the determination of antibodies in drug allergy].

PMID- 15435306
TI  - [Atypical chronic erythroblastosis].

PMID- 15435307
TI  - [Investigations on the prothrombin and accelerator-globulin content of the blood
      in liver disease].

PMID- 15435308
TI  - [Function test of the endocrine glands with short wave diathermy in regulated
      dosage].

PMID- 15435310
TI  - [Biological therapy of echinococcosis].

PMID- 15435309
TI  - [Visual field in glaucoma].

PMID- 15435311
TI  - [Case of common ileocolic mesentery].

PMID- 15435313
TI  - [The hand in medicine and in art].

PMID- 15435312
TI  - [Acute abdomen in postoperative gynecological complications and particularly in
      certain technics practiced for the treatment of uterine retroversion].

PMID- 15435314
TI  - [Recent advances in the pathogenesis and treatment of essential hypertension].

PMID- 15435315
TI  - [Diagnosis and treatment of functional indigestion].

PMID- 15435316
TI  - [Subcortical frontal leukotomy].

PMID- 15435317
TI  - [Prophylaxis of psychic anorexia; feeding technic and education of the infant].

PMID- 15435318
TI  - [Vocation].

PMID- 15435319
TI  - [The 4 periods of Mall; evolution of intestinal sutures].

PMID- 15435320
TI  - [Hemotherapy in hemorrhage of digestive origin].

PMID- 15435321
TI  - [Duodenal ulcer; its radiological picture].

PMID- 15435322
TI  - [Career of dietitian in the United States].

PMID- 15435323
TI  - [Physiology and menstrual disorders].

PMID- 15435324
TI  - [Plastic treatment of pyeloureteral obstruction; personal experience].

PMID- 15435325
TI  - [Anesthesia of the upper cervical ganglion].

PMID- 15435326
TI  - [Lesions in the locomotor system due to brucellosis].

PMID- 15435327
TI  - [Parrot's pseudoparalysis and penicillin; tolerance to massive doses].

PMID- 15435328
TI  - [The cecal anus].

PMID- 15435329
TI  - [Considerations on several cases of typhoid].

PMID- 15435330
TI  - [The world against poliomyelitis].

PMID- 15435331
TI  - [Radium therapy of angiomas].

PMID- 15435332
TI  - [Treatment of fractures of the face].

PMID- 15435333
TI  - [Streptomycin in the treatment of extrapulmonary tuberculosis].

PMID- 15435334
TI  - [Early ambulation].

PMID- 15435335
TI  - [Radiology of the normal and pathogenic prepyloric region].

PMID- 15435336
TI  - [Hematic disorders produced by sodium salicylate; its preventive and remedial
      treatment with vitamin K].

PMID- 15435337
TI  - [Treatment of axillary hydrosadenitis; letter to a country doctor].

PMID- 15435338
TI  - [Progress in the manufacture of artificial limbs].

PMID- 15435339
TI  - [Acute abdomen].

PMID- 15435340
TI  - [Natural and artificial collateral circulation].

PMID- 15435341
TI  - [Differential diagnosis of lead poisoning; approved laboratory criteria].

PMID- 15435342
TI  - [Vocation and its Brahmans].

PMID- 15435343
TI  - [Treatment of hepatic cirrhosis].

PMID- 15435344
TI  - [Premenstrual intoxication].

PMID- 15435345
TI  - [Treatment of echinococcosis; hepatic hydatid cysts].

PMID- 15435346
TI  - [Shoulder injuries; Dehene's etiological classification].

PMID- 15435347
TI  - [Traumatology in Tandil, Argentina].

PMID- 15435348
TI  - [Prostatic surgery in Tandil, Argentina].

PMID- 15435349
TI  - [2 cases of abscess of the lung].

PMID- 15435350
TI  - [History of a patient operated on in 1897 by Alejandro Posadas].

PMID- 15435351
TI  - [Pseudomucous cystoma of the ovary].

PMID- 15435352
TI  - [Grisel's syndrome].

PMID- 15435353
TI  - [Elements of prognosis in heart block; 58 cases].

PMID- 15435354
TI  - [A new hereditary mouth abnormality in a family].

PMID- 15435355
TI  - [Pediatrics in Tandil, Argentina].

PMID- 15435356
TI  - [A new property of heparin: its antiexudative action].

PMID- 15435357
TI  - [The serology of syphilis].

PMID- 15435358
TI  - [Endoscopic treatment of the severe asthma attack].

PMID- 15435359
TI  - [Current ideas on cancer of the breast].

PMID- 15435360
TI  - [The specialized teaching of abdominal surgery].

PMID- 15435361
TI  - [Scope and limitations of radiology].

PMID- 15435362
TI  - [Simultaneous plastic operations on the cranium with pliofil and stainless steel;
      an interesting case of epilepsy].

PMID- 15435363
TI  - [Psychosomatic investigations in ophthalmology].

PMID- 15435364
TI  - [Our experience with BCG vaccination in Capilla del Monte].

PMID- 15435365
TI  - [Inverted cecum].

PMID- 15435366
TI  - [Cutaneous manifestations of chronic intestinal amebiasis].

PMID- 15435367
TI  - [Penicillin therapy in gynecology].

PMID- 15435368
TI  - [Allergic paroxysmal tachycardia].

PMID- 15435369
TI  - [Stenosing supravaterian periduodenitis].

PMID- 15435370
TI  - [Ligature of the superior longitudinal sinus; 7 cases; operative technic and
      secondary cerebral dysfunction].

PMID- 15435371
TI  - [Desoxycorticosterone and rheumatic diseases].

PMID- 15435372
TI  - [Pharmacology and therapy of vitamins E and K].

PMID- 15435373
TI  - [Hanging cast in fractures of the upper end of the humerus].

PMID- 15435374
TI  - [Case of Stajano syndrome].

PMID- 15435375
TI  - [Tuberculous plastic peritonitis with ileal stenosis].

PMID- 15435376
TI  - [Congenital stenosis of the pulmonary artery].

PMID- 15435377
TI  - [Vocation and contagion].

PMID- 15435378
TI  - [Medico-surgical treatment of tuberculosis].

PMID- 15435379
TI  - [Drug allergies].

PMID- 15435380
TI  - [Modification of the classical technic of preparing histological specimens;
      inclusion in paraffin, rapid method].

PMID- 15435381
TI  - [The Instituto de Medicina Experimental, Buenos Aires; its function as a cancer
      investigation center].

PMID- 15435382
TI  - [Program for the study of deficiency diseases in infants and children].

PMID- 15435383
TI  - [Cutaneous tuberculosis primary complex in a child].

PMID- 15435384
TI  - [Chronic conjunctivitis and its treatment].

PMID- 15435386
TI  - [Narcoanalysis].

PMID- 15435385
TI  - [Hemostatic nephrectomy].

PMID- 15435387
TI  - [Pathogenesis of essential hypertension and malignant sclerosis].

PMID- 15435388
TI  - [Course in roentgenotherapy].

PMID- 15435389
TI  - [Pentothal-curare association in surgery].

PMID- 15435390
TI  - [Physiotherapy treatment with ultrasonic waves; clinical observations].

PMID- 15435391
TI  - [Surgical aspects of cancer of the rectum].

PMID- 15435392
TI  - [Travel notes; 35th annual meeting of the American College of Surgeons and the
      6th Inter-American Congress of Surgery].

PMID- 15435393
TI  - [Di-chloro-oxyquinaldine as a local medication; evaluation of results].

PMID- 15435394
TI  - [Recurrent pyelonephritis].

PMID- 15435395
TI  - [Hemorrhagi forms of epidemic cerebrospinal meningitis; the Waterhouse
      Friderichsen syndrome].

PMID- 15435396
TI  - [Prophylaxis of buccodental diseases].

PMID- 15435397
TI  - [Diagnosis and abuse of diagnosis of Malta fever].

PMID- 15435398
TI  - [Gastrectomy in cancer of the stomach].

PMID- 15435399
TI  - [Halogenated proteins in the treatment of the cardiovascular complications of
      myxedema].

PMID- 15435400
TI  - [Art and medicine].

PMID- 15435401
TI  - [Advantages of a school of hemotherapy].

PMID- 15435402
TI  - [Preoperative treatment of hyperthyroidism].

PMID- 15435403
TI  - [Atmospheric ionization and allergic conditions].

PMID- 15435404
TI  - [Ovarian micropolycystosis; diagnosis and treatment].

PMID- 15435405
TI  - [Dynamic theory and early treatment of distal nephron nephrosis].

PMID- 15435406
TI  - [Reiter's syndrome; a case].

PMID- 15435407
TI  - [Spinal anesthesia in the service of Prof. Diez; treatment].

PMID- 15435408
TI  - [Acute extrapyramidal syndrome following use of chloromycetin].

PMID- 15435409
TI  - [Fundamentals and general principles of anti-rheumatism therapy].

PMID- 15435410
TI  - [Surgical collapsotherapy and streptomycin; dissemination and reactivation].

PMID- 15435411
TI  - [Surgery in stenosis of the pulmonary artery].

PMID- 15435412
TI  - [Painful intrasinus uronephrosis; enervation and nephropexia; cure].

PMID- 15435413
TI  - [Childhood and vocation].

PMID- 15435414
TI  - [Giant intramedullary astrocytoma in a child].

PMID- 15435415
TI  - [New case of pellagra].

PMID- 15435416
TI  - [Skin factors of the vitamin B2 complex].

PMID- 15435417
TI  - [Intravenous procaine therapy].

PMID- 15435419
TI  - [Angiocardiography in Sweden].

PMID- 15435418
TI  - [Electrophoretic study of plasma proteins in cancer].

PMID- 15435420
TI  - [Kinesiology; teaching and application].

PMID- 15435421
TI  - [Leptospirosis].

PMID- 15435423
TI  - [Degenerative lesions in diabetes].

PMID- 15435422
TI  - [Treatment of tuberculous abscesses and fistulas with streptomycin and p
      aminosalicylic acid].

PMID- 15435424
TI  - [Treatment of cerebral hemorrhage; importance of oxygen].

PMID- 15435425
TI  - [Treatment of pneumococcic meningitis by penicillin and the sulfonamides].

PMID- 15435426
TI  - [Roentgenotherapy course; small intestine].

PMID- 15435427
TI  - [Suggestions for phthisiologists].

PMID- 15435428
TI  - [Time element in disease].

PMID- 15435429
TI  - [Specialization in medicine].

PMID- 15435430
TI  - [Medication by insulin].

PMID- 15435431
TI  - [The adaptation syndrome; its relation to human physiopathology].

PMID- 15435432
TI  - [Hepatorenal syndrome].

PMID- 15435433
TI  - [Respiratory function tests; normal volumetric indexes].

PMID- 15435434
TI  - [Therapeutic guide for intestinal parasitic diseases; amebiasis].

PMID- 15435435
TI  - [Conclusion of the Second International Asthma Congress].

PMID- 15435436
TI  - [Treatment of venous thrombosis].

PMID- 15435438
TI  - [Seventh International Congress of Surgery].

PMID- 15435437
TI  - [Tubal otorrhea in infants, treated by nasopharyngeal instrumental expression].

PMID- 15435439
TI  - The use of PAS in the treatment of draining tuberculous empyemata.

PMID- 15435440
TI  - Endoscopic collection of neoplastic cells and tubercle bacilli from the bronchi;
      description of a new irrigation-suction collector and the anatomical,
      physiological, and pathological factors involved.

PMID- 15435441
TI  - The significance of unstable tuberculin reactions.

PMID- 15435442
TI  - Pulmonary diseases service rehabilitation program of a Veterans Administration
      hospital.

PMID- 15435443
TI  - The shrunken right middle lobe, with reference to the so-called "middle lobe
      syndrome".

PMID- 15435444
TI  - Experimental massive pulmonary collapse.

PMID- 15435445
TI  - Benign thymic cyst: a case report.

PMID- 15435446
TI  - Metastatic malignant tumors to the bronchus found in bronchial biopsy and
      secretions.

PMID- 15435447
TI  - Autopsy incidence of pulmonary embolism in tuberculosis.

PMID- 15435448
TI  - Early detection of bronchogenic carcinoma.

PMID- 15435449
TI  - Sarcoidosis.

PMID- 15435450
TI  - Treatment of tuberculous meningitis with streptomycin.

PMID- 15435451
TI  - Artificial pneumoperitoneum in the treatment of pulmonary emphysema; a
      preliminary report.

PMID- 15435452
TI  - Pulmonary resection and streptomycin in the treatment of pulmonary tuberculosis.

PMID- 15435453
TI  - Middle lobe disease.

PMID- 15435454
TI  - Professor Manoel de Abreu receives College Medal.

PMID- 15435455
TI  - [Role of the endocrine glands in rheumatoid arthritis].

PMID- 15435456
TI  - [Fatal cerebral apoplexy at term].

PMID- 15435457
TI  - [Two cases of inverted uterus].

PMID- 15435458
TI  - [Kidney injury due to sulfathiazole (lower nephron nephrosis)].

PMID- 15435459
TI  - [Observations on hereditary somatic diseases and their incidence in Finland].

PMID- 15435460
TI  - [A case of full-term ovarian pregnancy].

PMID- 15435461
TI  - [The effect of storage of BCG vaccine upon the development of a positive reaction
      following inoculation].

PMID- 15435462
TI  - [Streptomycin therapy of tuberculous pericarditis].

PMID- 15435463
TI  - [An interview with Oskar Reinikainen, chief of the Ministry for Medicine].

PMID- 15435465
TI  - Thoughts on the study of medicine.

PMID- 15435464
TI  - [Society for the prevention of venereal disease (Reg. Assoc.)].

PMID- 15435466
TI  - Survey of the Kerio Valley.

PMID- 15435467
TI  - Chloromycetin and primary atypical pneumonia.

PMID- 15435468
TI  - Fatal spider bite.

PMID- 15435469
TI  - The immunity status of Nairobi school children as shown by 1798 Schick tests.

PMID- 15435470
TI  - [Radiology of pulmonary edema; definition of alveolar and interstitial edema in
      determination of radiologic pictures].

PMID- 15435471
TI  - [Salmonellosis in the north of France].

PMID- 15435472
TI  - [Tuberculous meningitis of the child; present therapeutics].

PMID- 15435473
TI  - [Insufficiency of the treatment of tuberculous meningitis by intra-muscular
      injections of streptomycin].

PMID- 15435474
TI  - [Not Available].

PMID- 15435475
TI  - [Subacute malignant endocarditis resistant to penicillin].

PMID- 15435476
TI  - [Intravenous adrenalin in man; physio-pathologic study and therapeutic
      applications].

PMID- 15435477
TI  - [Angiocardiography in the analysis of pathologic median shadow; 13 cases].

PMID- 15435478
TI  - [Acute poisoning by sodium chlorate; anuria; exchange transfusions and peritoneal
      dialysis].

PMID- 15435479
TI  - [Habitual abortions].

PMID- 15435480
TI  - [Scapulo-humeral periarthritis treated by tetra-ethyl ammonium].

PMID- 15435481
TI  - [Amebic hepatitis of infrequent symptomatology; clinical and therapeutic
      considerations].

PMID- 15435482
TI  - The outlook for the diabetic.

PMID- 15435483
TI  - Benign papilloma of the cervix.

PMID- 15435484
TI  - A case of cyclic neutropenia.

PMID- 15435485
TI  - Public health in the United States.

PMID- 15435486
TI  - [Hallervorden-Spatz disease; two cases of progressive familial rigidity with
      anatomic examination].

PMID- 15435488
TI  - [Bioelectric constitution of hyper-emotivity].

PMID- 15435487
TI  - [Aphasia in Heller's infantile dementia].

PMID- 15435489
TI  - [Transference in group psychotherapy].

PMID- 15435490
TI  - [Psychotics in the works of Eustache Deschamps].

PMID- 15435492
TI  - An immediate response of the demedullated adrenal gland to stress.

PMID- 15435491
TI  - An antidiuretic substance in the blood of normal and adrenalectomized rats.

PMID- 15435493
TI  - Renotropic effects of some androgens upon experimental hydronephrosis and upon
      the clitoris in the mouse.

PMID- 15435494
TI  - The glycostatic action of purified growth hormone.

PMID- 15435495
TI  - The ability of liver preparations and vitamin B12 to maintain thymus weight in
      thyroid-fed rats having greatly hypertrophied adrenal glands.

PMID- 15435496
TI  - Some effects of the hypophysis on iodine metabolism by the thyroid gland of the
      rat.

PMID- 15435497
TI  - The effect of hypophysectomy, adrenalectomy and of ACTH administration on the
      phosphorus metabolism of rats.

PMID- 15435498
TI  - Production of reversible hyperadrenocortinism in rats by prolonged administration
      of cortisone.

PMID- 15435499
TI  - Antagonism of estrogens by testosterone propionate in hypophysectomized female
      rats.

PMID- 15435501
TI  - [From physical deformity to neurosis].

PMID- 15435500
TI  - [The psychobiological concepts of M. Henri Wallon].

PMID- 15435502
TI  - [Nosography and shock therapy].

PMID- 15435504
TI  - [Case of anorexia nervosa].

PMID- 15435503
TI  - [Anxiety, existence and vitality].

PMID- 15435505
TI  - [Recent trends in American psychotherapy].

PMID- 15435506
TI  - The study of atomic processes with the photographic plate.

PMID- 15435507
TI  - [Problem of the actinide group of elements].

PMID- 15435508
TI  - [Cyclic compounds of thiourea].

PMID- 15435509
TI  - [Recent results in the study of graptoliths from the Gotlandium].

PMID- 15435510
TI  - [Cytochemical study of nucleated and nonnucleated fragments of amebae].

PMID- 15435511
TI  - [Bacteriostatic trichloroethylidene-ketones].

PMID- 15435512
TI  - [Phase contrast microscopy of the coagulocyte, coagulation islets and the
      coagulation of plasma in the blood of insects].

PMID- 15435513
TI  - [Duration of effect in experiments with a preparation of heparin for prolonged
      action].

PMID- 15435514
TI  - [Effect of the adrenocorticotropic hormone upon thrombocyte count].

PMID- 15435515
TI  - The role of histamine in leucocytosis.

PMID- 15435516
TI  - [Complimentary spectra].

PMID- 15435517
TI  - [Standard white].

PMID- 15435518
TI  - The deamination of djenkolic acid in rats.

PMID- 15435519
TI  - [Metabolism of adrenochrome and trihydroxymethylindole in the rabbit].

PMID- 15435520
TI  - [Parenchymal lipoidosis due to colchicine; difference in sensitivity of the sexes
      in intoxicated animals].

PMID- 15435521
TI  - Anti-adrenaline and anti-arterenol activity of some sympathicolytic compounds.

PMID- 15435522
TI  - [Iodine as a general developer in paper chromatography].

PMID- 15435523
TI  - Steric course of reactions of steroids.

PMID- 15435524
TI  - The conformation of the steroid nucleus.

PMID- 15435525
TI  - Sensitivity of the eustachian tube.

PMID- 15435526
TI  - Contact lens problems.

PMID- 15435527
TI  - Correction of facial deformity resulting from facial nerve paralysis.

PMID- 15435528
TI  - Sinus transillumination; elimination of dark room.

PMID- 15435529
TI  - Wolfe corneal scleral tonometer, model B.

PMID- 15435530
TI  - Absorption of nasal autogenous cancellous bone grafts.

PMID- 15435531
TI  - A new hand tangent screen.

PMID- 15435532
TI  - Incomplete glaucoma, monosymptomatic glaucomatous excavation.

PMID- 15435533
TI  - Modified nasal septum operations.

PMID- 15435534
TI  - Neomycin in the treatment of otitis media in infants.

PMID- 15435535
TI  - Management of retinal detachment.

PMID- 15435536
TI  - Nasal neurology in relation to local anesthesia in rhinoplasty.

PMID- 15435537
TI  - Atresia of the lacrymal puncta.

PMID- 15435538
TI  - [Mycostatic and mycocidal action of heterocyclic derivatives of obenzoquinone].

PMID- 15435539
TI  - [Trioses and pyruvic acid, intermediate products in the aerobic breakdown of
      pentoses with Torula utilis].

PMID- 15435540
TI  - [Activity of chloramphenicol and development of E. coli].

PMID- 15435541
TI  - [Some sulfanilamides].

PMID- 15435542
TI  - [Antibiotic activity of some derivatives of p-aminobenzoic acid toward tubercle
      bacilli and pertussis bacilli and synergistic action with vitamin K].

PMID- 15435544
TI  - [Determination of pyribenzamine in some pharmaceutical forms].

PMID- 15435543
TI  - [Characteristics of an aromatic nitrogen mustard; bis (2-chloroethyl)-beta
      naphthylamine].

PMID- 15435545
TI  - [Anticoagulants].

PMID- 15435546
TI  - [Vitamin B12; isolation of one of its products of degradation: 1-alpha-d
      ribofuranoside-5,6-dimethylbenzimidazole].

PMID- 15435547
TI  - [A new application of subtilin].

PMID- 15435548
TI  - [Extraction plants in the chemical pharmaceutical industry. III. Continuous
      extraction].

PMID- 15435549
TI  - [Preparation, characteristics and biological control of ACTH].

PMID- 15435550
TI  - [Chemical property and biological activity of protein hydrolysates for parenteral
      nutrition].

PMID- 15435551
TI  - [Hyaluronidase in pediatrics].

PMID- 15435552
TI  - [TB 1/698 in the therapy of tuberculosis].

PMID- 15435553
TI  - [Elimination phenomena of plants].

PMID- 15435554
TI  - [Medicinal drugs in the work of Fernando de Sepulveda].

PMID- 15435555
TI  - [Histological study of some species of the genus Asclepias: A. syriaca, A.
      sullivantii, A. grandiflora; histochemistry of some peculiarities of the leaf
      parenchyma of the above species].

PMID- 15435556
TI  - [Material conditions for the culture of plant tissues].

PMID- 15435557
TI  - [Cultivation of belladonna in Galicia].

PMID- 15435558
TI  - [Contribution to the study of Strophanthus of Spanish Guinea].

PMID- 15435559
TI  - [Acetyl index in tertiary alcohols].

PMID- 15435560
TI  - [Production of alkaloids by means of ion exchange resins. I. Alkaloids of
      belladonna].

PMID- 15435561
TI  - [Aromatic contact poisons which contain halogen].

PMID- 15435562
TI  - [Rheumatism before cortisone].

PMID- 15435563
TI  - [Physiology and pharmacology of nerve centers].

PMID- 15435564
TI  - [Cyclopropane and anesthesia].

PMID- 15435565
TI  - [Chemistry and pharmacology of antihistamines].

PMID- 15435567
TI  - [Mechanism of action of drugs].

PMID- 15435566
TI  - [Antihistamines and muscular activity].

PMID- 15435568
TI  - Studies related to the adrenal cortex.

PMID- 15435569
TI  - Protection of liver and kidneys by dietary factors choline and its precursors as
      lipotropic agents.

PMID- 15435570
TI  - Biochemical aspects of genetics.

PMID- 15435571
TI  - Biosynthesis of nucleic acids in the mammal.

PMID- 15435572
TI  - Chemical transformations of carbon in photosynthesis.

PMID- 15435573
TI  - Intermediates in photosynthesis.

PMID- 15435574
TI  - Hydrogenase activity and photoassimilation.

PMID- 15435575
TI  - Chemical transformations in photosynthesis.

PMID- 15435576
TI  - Chemical transformations in photosynthesis.

PMID- 15435577
TI  - Chemical transformations in photosynthesis.

PMID- 15435578
TI  - Decarboxylation and transamination.

PMID- 15435579
TI  - Signs of malnutrition seen in Newfoundland.

PMID- 15435580
TI  - Statistical appraisal of nutritional data.

PMID- 15435581
TI  - [Osteoarticular tuberculosis in children].

PMID- 15435582
TI  - [Slight trauma and paronychia].

PMID- 15435583
TI  - [Therapeutic diet in chronic gastritis].

PMID- 15435584
TI  - [Injuries caused by lightning].

PMID- 15435585
TI  - [Role of the feldsher in children summer health centers].

PMID- 15435586
TI  - [Physical development and effects of massage and physical exercise on young
      children].

PMID- 15435587
TI  - [Shrubs and trees as wind-breaks on collective farms].

PMID- 15435588
TI  - [Timofei Petrovich Krasnobaev].

PMID- 15435589
TI  - [Feeding of newborn in maternity homes].

PMID- 15435590
TI  - [Significance of serologic examination of the blood (dry plasma) in control of
      venereal diseases].

PMID- 15435592
TI  - [Recommended bibliography of contemporary literature for subprofessional medical
      personnel, 1940-1950; gastrointestinal infections].

PMID- 15435591
TI  - [Japanese, or tea, fungus].

PMID- 15435593
TI  - Ovarian resection for the relief of sterility.

PMID- 15435595
TI  - A new combined radiographic and gaseous technic in evaluating the status of the
      female genital tract.

PMID- 15435594
TI  - Problems in uterine physiology and their interrelations.

PMID- 15435596
TI  - The PSP (Speck) test for tubal patency.

PMID- 15435597
TI  - Time required for conception in 1727 planned pregnancies.

PMID- 15435598
TI  - The male factor in fertility and infertility; an analysis of ejaculate volume in
      800 fertile men and in 600 men in infertile marriage.

PMID- 15435599
TI  - Fructolysis of human spermatozoa.

PMID- 15435600
TI  - The extraction of hyaluronidase from human testicles and seminal fluid.

PMID- 15435601
TI  - [Dental service in school in Hungary].

PMID- 15435602
TI  - [The permeability of the enamel].

PMID- 15435604
TI  - [Gingivitis due to dental bridgework].

PMID- 15435603
TI  - [Correlation between fluoride content in water and dental caries; data on dental
      caries in school children in Szekszard].

PMID- 15435605
TI  - [Care of surgical patients in stomatologic departments].

PMID- 15435606
TI  - [Internal diseases caused by dental caries and paradentosis].

PMID- 15435607
TI  - [Report on dental service in the clinics in eastern Hungary].

PMID- 15435609
TI  - [Notes on helminthological technic].

PMID- 15435608
TI  - [Correlation between water fluorides and dental caries; comparison of dental
      caries in children born in Szekszard and children who were moved into the area
      after dentition].

PMID- 15435610
TI  - [Critical study of the treatment of hydrocele; comparison between the
      conservative and surgical methods].

PMID- 15435611
TI  - [New directions of obstetrics].

PMID- 15435612
TI  - [The family in relation to social psychiatric assistance in welfare
      institutions].

PMID- 15435613
TI  - [Reflexions on trypanosomiasis].

PMID- 15435614
TI  - [Notes on protozoological technic].

PMID- 15435615
TI  - [Social welfare for the neurotic].

PMID- 15435616
TI  - [Modern concept of surgery].

PMID- 15435617
TI  - [Preoperative treatment in prostate surgery].

PMID- 15435618
TI  - [Pellagra and other dermatoses observed in 1948 in the Juliano Moreira Colony].

PMID- 15435619
TI  - [Role of the hypophysis in carbohydrate metabolism and diabetes].

PMID- 15435620
TI  - [Histopathologic modifications of thiosemicarbazone in the thyroid gland;
      experimental study].

PMID- 15435621
TI  - [Inhibition of the mesenchymal defense reaction in experimental alloxan
      diabetes].

PMID- 15435622
TI  - [Modification of protidemia and of colloidal pressure of the blood in
      experimental hyperthyroidism].

PMID- 15435623
TI  - [Experimental contribution to the physiopathology of the median lobe of the
      hypophysis].

PMID- 15435624
TI  - [Pituitary corticotropic hormone in the therapy of arthropathy].

PMID- 15435625
TI  - [Urinary elimination of 17-ketosteroids after irradiation of the hypophysis].

PMID- 15435626
TI  - [Prothrombinemic values in Flajani-Basedow disease].

PMID- 15435627
TI  - [Three cases of malignant neoplasms of the reticular connective tissues of the
      thymus].

PMID- 15435628
TI  - [Not Available].

PMID- 15435629
TI  - BIBLIOGRAPHY of writings Professor B. Brouwer.

PMID- 15435630
TI  - [Not Available].

PMID- 15435631
TI  - [Projection of retinal quadrants in the optic radiation in a case of binocular
      hemianopsia].

PMID- 15435632
TI  - [Cerebellar encephalitis in two young cats].

PMID- 15435633
TI  - Subarachnoid haemorrhage and hemiplegia.

PMID- 15435634
TI  - A neutralization bridge in directly coupled push-pull amplifiers.

PMID- 15435635
TI  - Mental disorders with tumours of the pons.

PMID- 15435637
TI  - On the configuration and the connections of the medioventral area and the midline
      cells in the thalamus of the rabbit.

PMID- 15435636
TI  - Afferent verve fibres from the hypophysis to the tuber cinereum.

PMID- 15435638
TI  - The classification of diffuse demyelinating sclerosis of the brain on the basis
      of pathogenesis.

PMID- 15435639
TI  - [Coordination of morphologic and physiologic investigation technics in brain
      research].

PMID- 15435640
TI  - [Description and surgery of a case of trigono-oxycephaly].

PMID- 15435641
TI  - Pure word blindness.

PMID- 15435642
TI  - [Not Available].

PMID- 15435643
TI  - [On concussion of the spinal cord].

PMID- 15435644
TI  - The cause of loss of consciousness in posterior fossa compressions.

PMID- 15435645
TI  - Chronic experimental hyperalgesia in cats.

PMID- 15435646
TI  - [Atypical forms of cleidocranial dysostosis; cranial dystosis without clavicular
      dysostosis].

PMID- 15435647
TI  - A not hitherto described variety of Krabbe's infantile form of diffuse hereditary
      brain-sclerosis.

PMID- 15435648
TI  - Malignant tumors of the ethmoid simulating olfactory groove meningioma's.

PMID- 15435650
TI  - [Clinical and pathologic aspects of toxoplasmosis in man].

PMID- 15435649
TI  - Observations on the anatomy of memory.

PMID- 15435651
TI  - The surgical treatment of the dyskinesias.

PMID- 15435652
TI  - On the toxic effects of penicillin on the nervous system.

PMID- 15435653
TI  - [Experimental studies on the cortical-oculogyric pathways of vertical eye
      movement].

PMID- 15435654
TI  - Von Recklinghausen's disease in identical twins.

PMID- 15435655
TI  - A case of dystrophia myotonica developing 15 years after poliomyelitis.

PMID- 15435656
TI  - [Hyperostosis of the petrous bone].

PMID- 15435657
TI  - Behavioral alterations following lesions of the medial surface of the temporal
      lobe.

PMID- 15435658
TI  - Tumours in the foramen magnum.

PMID- 15435659
TI  - Diagnosis and operative treatment of extra-medullary intra-dural tumors.

PMID- 15435660
TI  - Surgical treatment of syringopontobulbia and of cysts of the thalamus.

PMID- 15435661
TI  - [Apparatus for universal body section radiography].

PMID- 15435662
TI  - [Simultaneous angiocardiotomography].

PMID- 15435663
TI  - [Anomalies of aortic development and position].

PMID- 15435664
TI  - [Double aortic arch in man].

PMID- 15435665
TI  - [Roentgenography of arteria lusoria].

PMID- 15435667
TI  - [Tumors of the heart].

PMID- 15435666
TI  - [Roentgen symptomatology of adhesive pericarditis].

PMID- 15435668
TI  - [Roentgen topology of the bronchial tree].

PMID- 15435669
TI  - [Roentgen topology of the pulmonary segments].

PMID- 15435670
TI  - [Brucellar spondylitis].

PMID- 15435671
TI  - [Osteoporosis and diffuse plasmocytosis].

PMID- 15435672
TI  - [Roentgenography of hipjoint dislocation due to distention].

PMID- 15435673
TI  - [Roentgen tolerance dose].

PMID- 15435674
TI  - [Solitary cartilaginous exostosis, or solitary osteochondroma, of unusual
      localization].

PMID- 15435675
TI  - [Unusually large calcified echinococcic cyst of the liver].

PMID- 15435677
TI  - [Present treatment of acute leukosis].

PMID- 15435676
TI  - [Free moving foreign body (machine gun bullet) within a tuberculous cavity].

PMID- 15435678
TI  - [Attempt at a rational classification of anemias].

PMID- 15435679
TI  - [Diagnosis of hyperchromic anemias].

PMID- 15435680
TI  - [Hypersplenism].

PMID- 15435681
TI  - [Precise counting of eosinophils; Thorn's test].

PMID- 15435682
TI  - [Diagnosis and treatment of infantilism].

PMID- 15435683
TI  - [Complications of blood transfusion and their prevention].

PMID- 15435684
TI  - [Experimental investigations of alloxan poisoning in white mice, with a
      contribution to the problem of experimental murine amyloids].

PMID- 15435685
TI  - [Morphologic study of the effect of urethane in leukemia, malignant tumors of the
      lymphatic system, and lymphogranulomatosis].

PMID- 15435686
TI  - [Argyrophil epithelial cells of the human gastric mucosa].

PMID- 15435687
TI  - [Pathologicoanatomic findings in tuberculous leptomeningitis following clinical
      chemotherapy (streptomycin, TB IV, and BI 76 Tbc)].

PMID- 15435688
TI  - [Pathologico-anatomic observations on tuberculosis following treatment with TB
      I/698].

PMID- 15435689
TI  - [Electro-microscopic studies in the pathology of collagenous fibers].

PMID- 15435690
TI  - [Dysgerminoma with dermoid cyst; an unusual ovarian combination and its genetic
      aspects].

PMID- 15435691
TI  - [Investigations on the size of the liver-cell nucleus in normal and morbid states
      of white mice].

PMID- 15435692
TI  - Puzzling causes of weight loss.

PMID- 15435693
TI  - Nutrition in surgical patients.

PMID- 15435694
TI  - Intestinal obstruction.

PMID- 15435695
TI  - Pathology of hyperthyroidism.

PMID- 15435696
TI  - Gastrointestinal hemorrhage.

PMID- 15435697
TI  - The current digitoxin controversy.

PMID- 15435698
TI  - Seven rules for your bank account.

PMID- 15435699
TI  - Where are we camping tonight?

PMID- 15435700
TI  - Report of the Executive Secretary, St. Louis, Missouri, February 1950.

PMID- 15435701
TI  - MANUAL on the establishment and operation of a department of general practice in
      hospitals.

PMID- 15435702
TI  - Benign disease of the antral portion of the stomach.

PMID- 15435703
TI  - Portal cirrhosis; an analysis of 444 cases with notes on modern methods of
      treatment.

PMID- 15435704
TI  - The treatment of chronic ulcerative colitis with sodium hexadecyl sulfate.

PMID- 15435705
TI  - Patterns of response of gastric mucoprotein and acid to insulin; correlation with
      the underlying disease in the non-operated stomach of man.

PMID- 15435706
TI  - The continuous twelve-hour nocturnal gastric secretion in normal individuals and
      in patients with duodenal ulcer after a 24-hour fast.

PMID- 15435707
TI  - Pneumoperitoneum.

PMID- 15435708
TI  - Esophageal obstruction due to food impaction treated with caroid solution.

PMID- 15435709
TI  - Conditions affecting acid secretion by mouse stomachs in vitro.

PMID- 15435710
TI  - Toxicity of the mucigogue, eugenol, administered by stomach tube to dogs.

PMID- 15435711
TI  - The limitations of a gastric drainage operation upon the effectiveness of
      vagotomy.

PMID- 15435712
TI  - An instrument for gastrobiopsies.

PMID- 15435713
TI  - Eosinophilic infiltration of the stomach and bowel associated with pyloric
      obstruction and recurrent oesinophilia.

PMID- 15435714
TI  - Polyp of the first portion of the duodenum; case report.

PMID- 15435715
TI  - Pyloric adenoacanthoma; report of an additional case.

PMID- 15435716
TI  - The occurrence of chronic ulcerative colitis in twin males.

PMID- 15435717
TI  - Reticulum cell sarcoma of the stomach; report of a case in a young woman.

PMID- 15435718
TI  - The apparent adverse effect of dorsolumbar sympathectomy in the peptic ulcer
      patient.

PMID- 15435719
TI  - Gastro-intestinal mucosa in the wall of the human gall-bladder.

PMID- 15435720
TI  - The use of the Miller-Abbott tube in localizing occult gastrointestinal bleeding.

PMID- 15435721
TI  - Annular pancreas; report of a surgical case with a two year follow-up.

PMID- 15435722
TI  - Achlorhydria and duodenal ulcer; a report of 2 cases having achlorhydria and
      diagnosed as duodenal ulcer not proven at surgery.

PMID- 15435723
TI  - Presentation of the Julius Friedenwald Medal to Dr. B. B. Vincent Lyon.

PMID- 15435724
TI  - Obituary, Dr. Lee Connel Gatewood.

PMID- 15435725
TI  - Psychosomatic relationships in the digestive system.

PMID- 15435726
TI  - Review of gastric surgery for 1948.

PMID- 15435727
TI  - Studies in pancreatic function; a statistical study of pancreatic secretion
      following secretin in patients without pancreatic disease.

PMID- 15435728
TI  - The flocculation tests in the differential diagnosis of jaundice.

PMID- 15435729
TI  - Infectious hepatitis (homologous serum type) in drug addicts.

PMID- 15435730
TI  - Hookworm infection in veterans, with some notes on Strongyloides stercoralis and
      other parasites.

PMID- 15435731
TI  - The occurrence of proctologic disorders in infancy and childhood; a statistical
      review of 2700 cases.

PMID- 15435732
TI  - Changes in the gastroscopic appearance of the human stomach following intravenous
      tetra-ethyl ammonium chloride.

PMID- 15435733
TI  - Red goggle examination of superficial venous collaterals; a simple clinical
      substitute for the infrared photography.

PMID- 15435734
TI  - Gallstone ileus.

PMID- 15435735
TI  - Carcinoma of the gallbladder.

PMID- 15435736
TI  - Lesser peritoneal sac perforation complicating benign peptic ulcer; a clinical
      and roentgenologic study.

PMID- 15435737
TI  - Lesser peritoneal sac perforation complicating gastric carcinoma; report of 2
      cases.

PMID- 15435738
TI  - Serum amylase response to morphine, mecholyl and secretin as a test of pancreatic
      function.

PMID- 15435739
TI  - A histological investigation of the healing of acute gastric ulceration in the
      cat.

PMID- 15435740
TI  - The effect of banthine on gastric secretion in man and experimental animals.

PMID- 15435741
TI  - A comparison of the effectiveness of banthine and atropine in depressing gastric
      acid secretion in man and the dog.

PMID- 15435742
TI  - The effect of atropine on certain gastric functions in patients with duodenal
      ulcer.

PMID- 15435743
TI  - Carcinoma of esophagus complicating cardiospasm; report of a case.

PMID- 15435744
TI  - Benign ulcer of the greater curvature of the stomach; report of a case.

PMID- 15435745
TI  - Meckel's diverticulum producing chronic intestinal obstruction.

PMID- 15435746
TI  - The occurrence of peptic ulcer in eight siblings of one family.

PMID- 15435747
TI  - Paroxysma nocturnal hemoglobinuria (Marchiafava-Micheli syndrome); report of
      case.

PMID- 15435748
TI  - Involvement of the stomach in familial polyposis of the gastro-intestinal tract;
      report of a family.

PMID- 15435749
TI  - Amebic granuloma (ameboma) simulating carcinoma.

PMID- 15435750
TI  - Primary adenocarcinoma of the third portion of the duodenum.

PMID- 15435751
TI  - [Physiopathology of blood coagulation; basis of the comprehension of thrombosis
      and anticoagulant therapy].

PMID- 15435752
TI  - [Case of rupture and spontaneous hematoma of the large oblique muscle of the
      abdomen].

PMID- 15435753
TI  - [Cancer of the thoracic esophagus; its treatment].

PMID- 15435754
TI  - [Postoperative cholangiography filling the whole biliary tract and the pancreatic
      ducts].

PMID- 15435755
TI  - [Elephantiasis nostras of the penis and scrotum; surgical therapy].

PMID- 15435757
TI  - [Treatment of exanthematic rickettsial diseases with aureomycin].

PMID- 15435756
TI  - [Esophagectomy, with total resection of the stomach, by a transpleural
      diaphragmatic route].

PMID- 15435758
TI  - [Hydantoin derivatives in the treatment of tetanus].

PMID- 15435759
TI  - [Aureomycin; bibliographical review].

PMID- 15435760
TI  - [Chemotherapy in perspective; principals and practice of local chemotherapy].

PMID- 15435761
TI  - [Chemotherapy in perspective; principles of administration in chemotherapy].

PMID- 15435762
TI  - [Case of vegetative aortitis due, with great probability to Salmonella typhi].

PMID- 15435763
TI  - [Tinea capitis caused by a double infection from Trichophyton granulosum and
      Trichophyton violaceum].

PMID- 15435765
TI  - [Perifolliculitis capitis and abscedens suffodiens (illustration)].

PMID- 15435764
TI  - [Molluscum contagiosum of the scalp].

PMID- 15435766
TI  - [Milker's nodules].

PMID- 15435767
TI  - [Study of cerebrospinal fluid in human trypanosomiasis].

PMID- 15435768
TI  - [Osteosynthesis by metal with removable prosthesis].

PMID- 15435769
TI  - [Treatment of fractures of the leg by the Roger Anderson method].

PMID- 15435770
TI  - [Therapeutic pneumothorax; 100 cases].

PMID- 15435771
TI  - [Tuberculosis of the female genitals: clinical aspects, diagnosis, prognosis,
      treatment].

PMID- 15435772
TI  - [Present status of rhinoplasty; several cases].

PMID- 15435773
TI  - Electronics in medicine.

PMID- 15435774
TI  - [A biochemical process producing B1 avitaminosis].

PMID- 15435775
TI  - [Thoracic aortography; experimental study].

PMID- 15435776
TI  - [Oxygen therapy; precautions for nurses].

PMID- 15435777
TI  - [Inflammation of bone tissue of the jaw; circumscribed osteoperiostitis].

PMID- 15435778
TI  - [Duodenal abnormality due to a ring shaped pancreas].

PMID- 15435779
TI  - [Acute intestinal invagination after aortography; interpretation; practical
      deductions].

PMID- 15435780
TI  - [Present status of diagnosis and therapy of fetal erythroblastosis].

PMID- 15435781
TI  - [Gas gangrene following abortion].

PMID- 15435782
TI  - [Expediency of inducing labor in prolonged pregnancy].

PMID- 15435783
TI  - [Obstetric significance in uterus fixation; reply to Gross].

PMID- 15435784
TI  - [Ethinylestradiol therapy of the sequels of ovarian insufficiency].

PMID- 15435785
TI  - [Occurrence of "bright cells" in the endometrium].

PMID- 15435786
TI  - [Functional relationships between ovarian hilus cells and senile hyperplasia of
      the uterine mucosa].

PMID- 15435787
TI  - [Injuries of the symphysis during pregnancy and labor].

PMID- 15435788
TI  - [Cervicitis and electrocoagulation therapy].

PMID- 15435790
TI  - [Cervical pregnancy].

PMID- 15435789
TI  - [Coagulation therapy of refractory erosions of the portio].

PMID- 15435792
TI  - [Early diagnosis of pregnancy].

PMID- 15435791
TI  - [Endocrine osteopathy].

PMID- 15435794
TI  - [Definition and use of the frog unit in titration of gonadotropins].

PMID- 15435793
TI  - [Quantitative evaluation of gonadotropins using the male Rana esculenta].

PMID- 15435795
TI  - [Periodic fertility in the female based upon experience in analysis of the
      estrous cycle using temperature measurement].

PMID- 15435796
TI  - [Further results in the treatment of amenorrhea due to disorders of the central
      nervous system].

PMID- 15435798
TI  - [Results of active and conservative labor management in premature rupture of the
      fetal membranes].

PMID- 15435797
TI  - [Apparent effects of ecbolics].

PMID- 15435799
TI  - [Facial paralysis in pregnancy and labor].

PMID- 15435800
TI  - [Placental substances which influence metabolism].

PMID- 15435801
TI  - [Bedwetting and related conditions].

PMID- 15435802
TI  - [Liver integral and other clinico-chemical investigations of liver disease].

PMID- 15435803
TI  - [Epituberculosis; significance of tuberculosis of bronchial lymph nodes for
      primary pulmonary tuberculosis].

PMID- 15435804
TI  - Awareness of racial differences by preschool children in Hawaii.

PMID- 15435805
TI  - Age trends in children's evaluation of teacher-approved and teacher-disapproved
      behavior.

PMID- 15435806
TI  - Relationship between level of vocational aspiration and certain personal data: a
      study of some traits and influences bearing on the prestige level of vocational
      choice.

PMID- 15435807
TI  - [Moving pictures and mental hygiene].

PMID- 15435808
TI  - [Depth psychological aspects of neglect].

PMID- 15435809
TI  - [Early diagnosis of cancer of the female genitalia].

PMID- 15435810
TI  - [Thoughts on the crisis in medicine].

PMID- 15435811
TI  - [New treatment for rheumatics].

PMID- 15435812
TI  - [Industrial contracts and social security; recent developments in the U.S..].

PMID- 15435814
TI  - [The finances and accounts of social service institutions].

PMID- 15435813
TI  - [Occupational diseases in housekeeping].

PMID- 15435815
TI  - [International relations in social work].

PMID- 15435816
TI  - [Man and the machine; problems and aims of industrial psychology in Switzerland].

PMID- 15435817
TI  - [Various scientific approaches to hygiene and sanitation].

PMID- 15435818
TI  - [Toxic substances in the sewage of metal industries and protection of the water
      supply].

PMID- 15435819
TI  - [Toxicity of vapors of organic compounds of mercury (ethylmercurophosphate and
      ethylmercurochloride) in acute and chronic poisoning].

PMID- 15435820
TI  - [Protective clothing and its cleaning, for workers with mercury].

PMID- 15435821
TI  - [Alimentary heliotrophic toxicosis; toxic hepatitis with ascites].

PMID- 15435822
TI  - [Characteristics of vitamin content of vegetable products in the Odessa
      district].

PMID- 15435823
TI  - [Future problems of hygiene education and sanitary supervision in physical
      culture and sports].

PMID- 15435824
TI  - [Basic requirements for hygiene manuals for medical institutes].

PMID- 15435825
TI  - [Infestation of vegetables with helminth's eggs by irrigation with purified
      sewage water].

PMID- 15435826
TI  - [Spraying of refuse with calcium hypochlorite].

PMID- 15435827
TI  - [Fly control and composting of refuse].

PMID- 15435828
TI  - [Disinfection of freight trains].

PMID- 15435829
TI  - [Dichloroethane in disinfection and deratization].

PMID- 15435830
TI  - [Alkaline refuse of naphta industries as a disinfecting substance].

PMID- 15435831
TI  - [Toxicity of DDT dust for man].

PMID- 15435832
TI  - [Results of the work of the clinic of occupational pathology at the chair of
      industrial hygiene].

PMID- 15435833
TI  - [Method of isolation of DDT in food products].

PMID- 15435834
TI  - [Chemical composition of milk of cows in the Sverdlov district].

PMID- 15435835
TI  - [Gravimetric and quantitative methods of determination of dust in industry].

PMID- 15435836
TI  - [Chemistry of chlorinated drinking water containing ammonium salts].

PMID- 15435837
TI  - [Results of research of natural lighting of living quarters with northern and
      southern exposures].

PMID- 15435838
TI  - [Silicosis in porcelain industry and its control].

PMID- 15435839
TI  - [Use of petroleum soap solution in drilling].

PMID- 15435840
TI  - [Determination of working space on mechanized harvesters].

PMID- 15435841
TI  - [Certain methods in examination of market milk].

PMID- 15435842
TI  - [The role of school physicians].

PMID- 15435843
TI  - [Hygienic aspect of toys].

PMID- 15435844
TI  - [Comparative evaluation of the sanitary aspects of vegetables growing on
      irrigated- and nonirrigated fields with sewage].

PMID- 15435845
TI  - [Sanitary and bacteriologic investigation of sea water and sand on the shores of
      Odessa].

PMID- 15435846
TI  - [Sanitation and disinfection of airliners].

PMID- 15435847
TI  - [Portable laboratory for water analysis].

PMID- 15435848
TI  - [New method of lighting schools].

PMID- 15435849
TI  - [Screens for prevention of heat radiation in industrial furnaces].

PMID- 15435850
TI  - [Prevention of intestinal infections].

PMID- 15435851
TI  - [Loss of nutritional substances in canned macaroni products].

PMID- 15435852
TI  - [In memory of Prof. S. N. Stroganov].

PMID- 15435853
TI  - [The teaching and professional practice of gynecology and obstetrics].

PMID- 15435854
TI  - [Sterility of endocrine origin; etiology, diagnosis and therapy].

PMID- 15435855
TI  - [Treatment of genital prolapse; criterion and regional experience].

PMID- 15435856
TI  - [Social and legal considerations on abortion].

PMID- 15435857
TI  - [Psychosomatic medicine in gynecology and obstetrics; present concept,
      therapeutic conduct and orientation].

PMID- 15435858
TI  - [Extension and revision of the indications for cesarean section].

PMID- 15435859
TI  - [Abnormal uterine hemorrhage outside of pregnancy].

PMID- 15435860
TI  - [Abnormal uterine hemorrhages outside of pregnancy; classification and
      nomenclature of menstrual changes].

PMID- 15435861
TI  - [Hemorrhagic syndrome in pregnancy].

PMID- 15435863
TI  - [Pathogenesis and causal therapy of myoedema (idiomuscular contraction)].

PMID- 15435862
TI  - [Urea overload test in relation to glomerulo-tubular tests in clinical
      diagnosis].

PMID- 15435864
TI  - [The pancreas and tuberculosis].

PMID- 15435865
TI  - [Experimental research on the antibacterial action of bismuth in relation to its
      use in the treatment of inflammations of biliary, urinary and respiratory
      tracts].

PMID- 15435866
TI  - [Practical use of the various renal function tests].

PMID- 15435867
TI  - [Aureomycin and rachicentesis in the treatment of severe whooping cough].

PMID- 15435868
TI  - [A very rare case of retroperitoneal pseudomyxoma of probable appendicular
      origin].

PMID- 15435870
TI  - [The pathogenetic treatment of angina pectoris].

PMID- 15435869
TI  - [A new antibiotic: terramycin].

PMID- 15435871
TI  - [Recent acquisitions on the pathogenesis and therapy of diabetes mellitus].

PMID- 15435872
TI  - [Landis capillary test in allergic rhinitis; modifications induced by intravenous
      epinephrine therapy].

PMID- 15435873
TI  - [First clinical research on the use of sodium gentisate in acute articular
      rheumatism; activity, tolerance, secondary phenomena].

PMID- 15435874
TI  - [Pancreatic lithiasis].

PMID- 15435876
TI  - [Clinico-statistical data on malignant granuloma].

PMID- 15435875
TI  - [Possible lipotropic action of Acqua Santa of Chianciano].

PMID- 15435877
TI  - [New orientations in the pathogenetic problem of urticaria pigmentosa].

PMID- 15435878
TI  - [Further clinico-experimental research on the behavior of phlogogenic substances
      in lupus vulgaris during therapy with shock doses of vitamin D2].

PMID- 15435879
TI  - [Behavior of blood sedimentation rate in the presence of leprosy antigens].

PMID- 15435881
TI  - [Acute lichen ruber planus; clinical observations].

PMID- 15435880
TI  - [Rosacea syndrome complicated by multiple epithelioma].

PMID- 15435882
TI  - [Acrodermatitis continua (Hallopeau), extensive variety (Audry); contribution to
      the study of its relations to clinically allied conditions].

PMID- 15435883
TI  - [Acute exacerbation of chronic lupus erythematosus with fatal thrombocytopenic
      purpura].

PMID- 15435884
TI  - [Contribution to the study of corification of cadavers].

PMID- 15435885
TI  - [Antipyogenic action of p-aminosalicylic acid; in vivo and in vitro experiments].

PMID- 15435886
TI  - [Protective action of penicillin in experimental arsphenamine intoxication in the
      mouse].

PMID- 15435887
TI  - [Curative action of streptomycin in experimental syphilis in white mice].

PMID- 15435888
TI  - [Reaction of the cholemic calf to Mycobacterium tuberculosis, bovine type].

PMID- 15435890
TI  - [Origin of BCG].

PMID- 15435889
TI  - [Antituberculosis vaccination with BCG].

PMID- 15435891
TI  - [Control and precaution in the use of BCG].

PMID- 15435892
TI  - [Antituberculosis BCG vaccination in U.S.S.R..].

PMID- 15435893
TI  - [Antituberculosis vaccination and recent acquisitions in epidemiology of
      tuberculosis].

PMID- 15435894
TI  - [Use of BCG in Mexico].

PMID- 15435895
TI  - [BCG vaccination; experimental bases and latest results obtained in France].

PMID- 15435896
TI  - [BCG vaccination in South America].

PMID- 15435897
TI  - [Senator Dr. Antonio Bareggi].

PMID- 15435898
TI  - [Military service and social welfare].

PMID- 15435899
TI  - [Intercostal nerve block with anesthetic oil solution in treatment of rib
      fractures].

PMID- 15435900
TI  - [Isthmic origin of cardiotoxic thyroid diseases].

PMID- 15435901
TI  - [Gunshot fractures of the neck of the femur].

PMID- 15435902
TI  - [Relation pituitary tumors to psychic disorders].

PMID- 15435903
TI  - [Practical adaptation of the Kipp apparatus for multiple simultaneous dispensing
      of hydrogen sulfide].

PMID- 15435904
TI  - [Malaria in the Venetian provinces].

PMID- 15435905
TI  - [Survey of the water resources of Tripolitania and peculiar characteristics of
      the waters of that region].

PMID- 15435906
TI  - [Circulatory insufficiency; clinico-statistical remarks].

PMID- 15435907
TI  - [Examination of the cochleovestibular apparatus in diabetes mellitus; preliminary
      note].

PMID- 15435908
TI  - [Morbidity from tuberculosis in Venice and its estuary from 10 years of
      dispensary observations].

PMID- 15435909
TI  - [Spontaneous pneumothorax in a newborn].

PMID- 15435910
TI  - A glimpse of American obstetrics and gynaecology.

PMID- 15435911
TI  - Comparative physiology.

PMID- 15435912
TI  - Three medico-legal cases.

PMID- 15435913
TI  - Forensic medicine in Egypt.

PMID- 15435914
TI  - A note on the investigation of sudden death.

PMID- 15435915
TI  - [Statistics and follow-up studies of genital carcinoma treated at the Basel
      Gynecological Clinic from 1935 to 1945].

PMID- 15435916
TI  - [Significance of vaginal hysterectomy in surgical therapy of prolapse].

PMID- 15435917
TI  - A classification of primary ovarian tumors according to their histogenesis.

PMID- 15435918
TI  - [Effect of prenatal administration of vitamins B1 upon the efficacy of pituitrin
      in alleviating labor pains].

PMID- 15435919
TI  - Diagnosis, prophylaxis, and therapy of erythroblastosis foetalis.

PMID- 15435920
TI  - [Cancer of the female genitalia; casuistics and statistics from the Basel
      Gynecological Clinic, 1935-45; cancer of the genitalia and pregnancy; type and
      localization of metastases in cervical, uterine and ovarian cancer].

PMID- 15435921
TI  - [Experimental and laboratory investigation of ultraviolet irradiation in the
      treatment of vaginal trichomoniasis].

PMID- 15435922
TI  - A new prosthesis for making an artificial vagina after the method of Kirschner
      and Wager.

PMID- 15435923
TI  - Capillary permeability in late pregnancy toxemias.

PMID- 15435924
TI  - [Significance of the amniotic fluid and amnion in obstetrics].

PMID- 15435925
TI  - [Therapeutic use of vernix caseosa in care of premature infants].

PMID- 15435926
TI  - [Ovarian teratoblastoma and sacral teratoma].

PMID- 15435927
TI  - [Timely treatment of a tuberculous fecal fistula].

PMID- 15435928
TI  - [Action of roentgen rays on erythroblastosis in experimental lead poisoning].

PMID- 15435929
TI  - [Hematological modifications produced by vitamin B12 in pernicious anemia].

PMID- 15435930
TI  - [Atypical malignant lymphogranuloma and benign eosinophil granuloma of the lymph
      nodes].

PMID- 15435931
TI  - Endocrine exophthalmos (in Hebrew; English summary).

PMID- 15435932
TI  - Orthoptic treatment of squint (in Hebrew; English summary).

PMID- 15435933
TI  - Our experiences in surgical treatment of mental diseases (in Hebrew; English
      summary).

PMID- 15435934
TI  - Our psychosurgical experiences with special reference to the problem of
      indications (in Hebrew; English summary).

PMID- 15435935
TI  - [Developmental phases of infancy].

PMID- 15435936
TI  - [The meaning of play].

PMID- 15435937
TI  - [Stubborness and development of the will].

PMID- 15435938
TI  - [... as truly as I see thee, and thou me].

PMID- 15435939
TI  - [Feeding difficulties, especially loss of appetite, in small children].

PMID- 15435940
TI  - [Why the family system in children's homes].

PMID- 15435941
TI  - [Our child before he enters school].

PMID- 15435942
TI  - [Chronic disorders of the vertebral column: arthroses and herniated disks].

PMID- 15435943
TI  - [Diagnosis and surgical therapy of herniated lumbar disk].

PMID- 15435944
TI  - [Lumbosacral osteosynthesis in lumbar sciatica and lumbago of discal origin].

PMID- 15435945
TI  - [Examination of blood protein in 76 pathologic states exhibiting beta
      hyperglobulinemia, and its clinical significance].

PMID- 15435946
TI  - [Skin thermometry as a method in clinical examination of vasotonic substances;
      examination of a new vasodilator (Ciba 7337) and of niconacid, ronicol and
      trafuril (nicotinic acid preparations)].

PMID- 15435947
TI  - [Syphilitic aortitis; diagnostic and therapeutic aspects of 108 cases of aortitis
      based upon histologic examination].

PMID- 15435948
TI  - [Technic of the quantitative flocculation test in human serum, and determination
      of vital ionization by irradiation].

PMID- 15435949
TI  - [Disorders of the autonomic nervous system in poliomyelitis; disorders as a
      result of lesions in the autonomic centers of the brain stem].

PMID- 15435950
TI  - [Reticuloendotheliosis; successful radiotherapy of a severe case of Hand-Schuller
      Christian disease].

PMID- 15435951
TI  - [Hand-Schuller-Christian disease in infancy].

PMID- 15435952
TI  - [Comparative study of the water binding capacity of carob flour, carob meal,
      dehydrated carrots, potato flour, and cornstarch].

PMID- 15435953
TI  - [Cleidocranial dysostosis].

PMID- 15435954
TI  - [Pre- and postoperative capillaroscopy in congenital cardiac defects].

PMID- 15435955
TI  - [Blood picture in exanthema subitum, with special reference to the first phase].

PMID- 15435956
TI  - [Perniciosiform anemias of infants].

PMID- 15435957
TI  - [Protein deficiency dystrophy].

PMID- 15435958
TI  - [Herter's infantilism and sprue; catamnestic study of 22 cases of celiac
      disease].

PMID- 15435959
TI  - [Diagnosis of congenital pulmonary stenosis with defect of the interauricular
      septum].

PMID- 15435960
TI  - [Purpura fulminans with deficiency of Owren's Factor V and treatment with
      exchange transfusion].

PMID- 15435961
TI  - [Lipoid nephrosis in enzygotic twins].

PMID- 15435962
TI  - [Direct determination of membrane potential in medullated nerve fibres at rest
      and under stimulation].

PMID- 15435963
TI  - The photochemical action of ultra-violet light on isolated single nerve fibres.

PMID- 15435964
TI  - [Effect of aneurin upon isolated rat gut].

PMID- 15435965
TI  - [Relation between the effect of papaverine and autonomic function].

PMID- 15435966
TI  - [Measurement of transcapillary diffusion with radioactive tracers].

PMID- 15435967
TI  - [Role of amino acids in increasing the nutritive value of wheat flour].

PMID- 15435968
TI  - [Modification of the cytochrome-C content of the muscles at great altitudes].

PMID- 15435969
TI  - [Effect of desoxycorticosterone and 11-dehydro-17-hydroxycorticosterone upon
      plasma sodium in adrenalectomized rats].

PMID- 15435970
TI  - [Liberation of aneurin during vagal stimulation of the heart].

PMID- 15435971
TI  - [Historical and critical review of the problem of the propogation of waves in a
      compressible liquid enclosed in an elastic tube].

PMID- 15435972
TI  - [Rapidity of the propagation of pressure waves in static and circulating fluids
      in elastic tubes].

PMID- 15435973
TI  - [Electric cortical manifestations in sleep produced by stimulation of the
      hypnogenic center in the cat].

PMID- 15435974
TI  - [Positive effect of serum on the respiration of surviving tissue].

PMID- 15435975
TI  - [Problem of the so-called presphygmic interval].

PMID- 15435976
TI  - [Determination of lipoid hydrolysis during intestinal resorption].

PMID- 15435977
TI  - [Continuous registration of the blood supply and oxygen concentration in visceral
      surfaces with the reflex photocell].

PMID- 15435978
TI  - [Demonstration of physically induced modifications of the electrophoretic
      picture].

PMID- 15435979
TI  - [Differentiation between deficient factor V and excessive antithrombin].

PMID- 15435980
TI  - [Are there exceptions to Cannon's law of denervation?].

PMID- 15435981
TI  - [Potassium and carbohydrate metabolism of surviving muscle].

PMID- 15435982
TI  - [Electrooculography and electronystagmography in man].

PMID- 15435983
TI  - [Biologic synthesis of co-carboxylase].

PMID- 15435984
TI  - [Enzymes in benign and malignant tumors of the liver; arginase and histidase].

PMID- 15435985
TI  - [Enzymes in benign and malignant tumors of the liver; succinoxidase and
      cholinoxidase].

PMID- 15435986
TI  - [Enzymes of benign and malignant tumors of the liver; cholinesterase and
      tributyrinase].

PMID- 15435987
TI  - [Malaria in Serbia].

PMID- 15435988
TI  - [Malaria in the district of Vojvodina in Yugoslavia].

PMID- 15435989
TI  - [Malaria in the region of Podrinje in Yugoslavia].

PMID- 15435990
TI  - [Malaria in the region of Vranje in Yugoslavia].

PMID- 15435991
TI  - [Malaria in the region of Kosovo and Metohija in Yugoslavia].

PMID- 15435992
TI  - [Epidemiology of malaria in Macedonia].

PMID- 15435993
TI  - [Malaria in Jugoslavia].

PMID- 15435994
TI  - [Epidemiology of malaria in Dalmatia].

PMID- 15435995
TI  - [Epidemiology of malaria in Bosnia and Hercegovina].

PMID- 15435996
TI  - [Epidemiology of malaria in Montenegro].

PMID- 15435997
TI  - [Culture of malarial plasmodium].

PMID- 15435998
TI  - [Hibernation of A. maculipennis typicus and A. maculipennis messeae in Serbia].

PMID- 15435999
TI  - [Not Available].

PMID- 15436000
TI  - [Biologic races of Culex pipiens].

PMID- 15436001
TI  - [Use of nicotine compounds against Anopheles].

PMID- 15436002
TI  - [Malignant forms of malaria].

PMID- 15436003
TI  - [Kala-azar in Macedonia and Serbia; epidemiologic and geographic aspect].

PMID- 15436004
TI  - [Epidemiology of kala-azar in Montenegro].

PMID- 15436005
TI  - [Kala-azar in Dalmatia].

PMID- 15436006
TI  - [Phlebotomus as a carrier of kala-azar].

PMID- 15436007
TI  - [Leishmaniasis; a review].

PMID- 15436008
TI  - [Bibliography of leishmaniasis].

PMID- 15436009
TI  - [Cutaneous leishmaniasis].

PMID- 15436010
TI  - [Teaching of preventive medicine in medical schools].

PMID- 15436011
TI  - [Analysis of infectious disease and epidemiologic examination].

PMID- 15436012
TI  - [Water supply and garbage disposal].

PMID- 15436013
TI  - [Problems of focal infection].

PMID- 15436014
TI  - [Sociopolitical and sociohygienic significance of rheumatism].

PMID- 15436015
TI  - [Whole meal mush, a forgotten basic nutrient].

PMID- 15436016
TI  - [Unusual case of full-term pregnancy in duplex uterus].

PMID- 15436017
TI  - [Psychotherapy of cardiospasm].

PMID- 15436018
TI  - [Relief of pain by diversion of the stimulus].

PMID- 15436019
TI  - [Indications and use of the cupping glass].

PMID- 15436020
TI  - [The organic view in medicine].

PMID- 15436021
TI  - [Logic].

PMID- 15436022
TI  - [What the practitioner should know about malaria].

PMID- 15436023
TI  - [Artemisia abrotanum (southernwood)].

PMID- 15436024
TI  - [Constitution and peptic ulcer].

PMID- 15436025
TI  - [Treatment of asthma with normal vaccine].

PMID- 15436026
TI  - [Postwar impotence].

PMID- 15436027
TI  - [Is there a reason for the appearance of dental caries?].

PMID- 15436028
TI  - [Natural remedies; mechanism and technic].

PMID- 15436029
TI  - [Phantom sensation and anatomical pattern; a study in the regression of the
      phantom limb].

PMID- 15436030
TI  - [Active relaxation therapy].

PMID- 15436031
TI  - [What the general practitioner should know about malaria; medicinal therapy].

PMID- 15436032
TI  - [Remedial effect of sinusoidal electrical stimulation of the vasomotor muscle
      cells in hypotonic states].

PMID- 15436033
TI  - [Effect of vegomed on the circulation].

PMID- 15436034
TI  - [Spagirics].

PMID- 15436035
TI  - [Basic concepts of iridodiagnosis].

PMID- 15436036
TI  - [Problems and research in nutrition, with special reference to the importance of
      bread].

PMID- 15436037
TI  - [Dietary significance of iodine].

PMID- 15436038
TI  - [The vitamin B complex].

PMID- 15436039
TI  - [Right and wrong in dietetics].

PMID- 15436040
TI  - [Schroth's treatment for present practice].

PMID- 15436041
TI  - [Chlorophyllin as an insulin activator].

PMID- 15436042
TI  - [Use of dyes in the preparation of drugs and cosmetics].

PMID- 15436043
TI  - [The problem of caries from the dentist's point of view].

PMID- 15436045
TI  - [Nephrosclerosis].

PMID- 15436044
TI  - [In memory of Prof. Franz Volhard].

PMID- 15436046
TI  - [Letter of an old doctor to a young colleague].

PMID- 15436047
TI  - [Diagnostic and therapeutic significance of Head's and Mackenzie's zones].

PMID- 15436048
TI  - [Meaning and purpose of recuperation; research in physiological rhythm].

PMID- 15436049
TI  - [Essential points of Kneipp's theory].

PMID- 15436050
TI  - [Treatment of stump contractures with Dicke's connective-tissue massage].

PMID- 15436051
TI  - [Closing address at the Munich Psychologic Congress].

PMID- 15436052
TI  - [Rademacher's system].

PMID- 15436053
TI  - [Examination of Head's zones in diseases of the abdomen].

PMID- 15436054
TI  - [Prophylaxis of dental caries].

PMID- 15436056
TI  - [Curare and anesthesia].

PMID- 15436055
TI  - [Unusual injuries of the bladder].

PMID- 15436057
TI  - [Syphilitic meningitis; a case].

PMID- 15436058
TI  - [In memory of Dr. Manuel Vela Gonzalez].

PMID- 15436059
TI  - [Elementary ophthalmologica practice; 4 problems of interest to the physician].

PMID- 15436060
TI  - [Acuphene and its effects].

PMID- 15436061
TI  - [Diagnostic value of skin puncture with B.C.G..].

PMID- 15436062
TI  - [Treatment of tuberculosis with p-aminosalicylic acid].

PMID- 15436063
TI  - [Moment in which streptomycin begins to act in experimental tuberculosis of the
      guinea pig].

PMID- 15436064
TI  - [Allergic pulmonary manifestations during penicillin therapy].

PMID- 15436065
TI  - [BCG vaccination in the Republic of Ecuador].

PMID- 15436066
TI  - [Radiological aspects of intestinal tuberculosis treated with streptomycin].

PMID- 15436067
TI  - [Incipient forms of pulmonary tuberculosis in adults].

PMID- 15436068
TI  - [Tuberculosis as a cause of death in America].

PMID- 15436069
TI  - [Tuberculin sensitivity and seasons of the year].

PMID- 15436070
TI  - [Institutional mortality from tuberculosis in Montevideo].

PMID- 15436071
TI  - [Ninth Congress of the Homeopathic Center of France, Paris, 15-19 May 1950].

PMID- 15436073
TI  - [Homeopathy and modern medicine].

PMID- 15436072
TI  - [Clinical homeopathy and therapeutic technic].

PMID- 15436074
TI  - [Erythema solare].

PMID- 15436075
TI  - [Extreme dilutions of homeopathic remedies].

PMID- 15436076
TI  - [New ideas on occupational dermatoses].

PMID- 15436077
TI  - [Pyorrhea].

PMID- 15436078
TI  - [Clinical study of pellagra].

PMID- 15436079
TI  - [Acute tumors of the pons vavolii].

PMID- 15436080
TI  - [New technic in the treatment of Sydenham's chorea by pyretotherapy].

PMID- 15436081
TI  - [Mass BCG vaccination].

PMID- 15436082
TI  - [Erythrocyte count of adolescent workers of both sexes, aged 14-17, in Rio de
      Janeiro].

PMID- 15436083
TI  - [Early ambulation in 100 cases of abdominal surgery].

PMID- 15436084
TI  - [Presence of hyalin spheres in the anterior pituitary and in the choroid plexus].

PMID- 15436085
TI  - [Extensive cicatricial stenosis of the larynx].

PMID- 15436086
TI  - [Giant infected hydronephrosis].

PMID- 15436087
TI  - [Genitourinary lesions in schistosomiasis mansoni].

PMID- 15436088
TI  - [Intrathoracic goiter; a case with extension to the diaphragm].

PMID- 15436089
TI  - [Blastomycosis in the Amazon Valley (keloidian and South American)].

PMID- 15436090
TI  - [Urological complications of carcinoma of the rectosigmoid].

PMID- 15436091
TI  - [Bone grafts; repair of losses of substance of bone and cartilage; principles].

PMID- 15436092
TI  - [Treatment of alcoholism with antabuse (tetraethylthiuram disulfide); importance
      of acetaldehyde].

PMID- 15436093
TI  - [Thrombotic obliteration in the aortic bifurcation].

PMID- 15436094
TI  - [Recent progress in typhoid fever].

PMID- 15436095
TI  - [Action of terramycin in bouba (frambesia, pian, yaws)].

PMID- 15436096
TI  - [Radical surgery in the treatment of tumors of the bladder].

PMID- 15436097
TI  - [Technic of BCG vaccination in Rio de Janeiro, Brazil].

PMID- 15436098
TI  - [Some aspects of the medical profession in Sweden].

PMID- 15436099
TI  - Regional planning to insure better patient care.

PMID- 15436100
TI  - The program of the regional council.

PMID- 15436101
TI  - Superiorship and hospital administration.

PMID- 15436102
TI  - The role of the diocesan director.

PMID- 15436103
TI  - MONEY alone builds no hospitals.

PMID- 15436104
TI  - How to use factual data to plan wisely.

PMID- 15436106
TI  - WHAT statistics reveal about the small Catholic hospital.

PMID- 15436105
TI  - How one small hospital serves its community.

PMID- 15436107
TI  - Personnel--key to effective nursing care.

PMID- 15436108
TI  - Organic transplantation.

PMID- 15436109
TI  - Busy month in Washington.

PMID- 15436110
TI  - [Suggestions concerning staff housing at a sanatorium].

PMID- 15436112
TI  - [Private and industrial food supply].

PMID- 15436111
TI  - [Nature of psychologic counsel].

PMID- 15436113
TI  - [Soap or synthetic products].

PMID- 15436114
TI  - [Importance of calcium for the organism].

PMID- 15436115
TI  - [Control, lack of control, and integrated personality].

PMID- 15436116
TI  - The issues in federal health legislation.

PMID- 15436117
TI  - A camera in the nursery.

PMID- 15436118
TI  - Chest x-rays plus routine laboratory examinations.

PMID- 15436119
TI  - Recruiting workers through school guidance counselors.

PMID- 15436120
TI  - Manual on nursing service will promote uniformity.

PMID- 15436122
TI  - ELEMENTS of hospital operation. opp.

PMID- 15436121
TI  - Setting up a postoperative recovery room.

PMID- 15436123
TI  - A tuberculosis hospital for mental patients.

PMID- 15436124
TI  - To answer the question: How good are trustees?

PMID- 15436125
TI  - Careful buying is essential for good public relations.

PMID- 15436127
TI  - NEED for a psychiatric unit in the general hospital.

PMID- 15436126
TI  - Preventive maintenance begins on the architect's blueprint.

PMID- 15436128
TI  - Proper spending can reduce the costs of laundry operation.

PMID- 15436129
TI  - Some procedures for establishing a hospital dietary department.

PMID- 15436130
TI  - MASTER menus for August.

PMID- 15436131
TI  - Some case histories of fire inspection; here are the deficiencies that showed up
      in early reports on hospitals in one state.

PMID- 15436132
TI  - The heat pump: one unit for year-round air conditioning.

PMID- 15436133
TI  - A county-wide sales tax finances construction.

PMID- 15436134
TI  - Nursing education: what it costs the hospital.

PMID- 15436135
TI  - There is no exploitation.

PMID- 15436136
TI  - Cost studies tell the story.

PMID- 15436137
TI  - Salesmanship for careers in the field of health.

PMID- 15436138
TI  - Supervisory conferences.

PMID- 15436139
TI  - Penny-a-day fund raising.

PMID- 15436141
TI  - NEW movie short helps to tell the hospital story.

PMID- 15436140
TI  - The general practitioner in hospital staff organization.

PMID- 15436142
TI  - A CONVENTION panel on small hospital problems.

PMID- 15436143
TI  - A system for central control of tuberculosis.

PMID- 15436144
TI  - Disease control through proper housekeeping.

PMID- 15436145
TI  - The benefits of a fulltime state association program.

PMID- 15436147
TI  - Flexibility through job rotation.

PMID- 15436146
TI  - The stages of a successful drive for efficient laundry operation.

PMID- 15436148
TI  - A study of maintenance accidents and some ways to avoid them.

PMID- 15436149
TI  - THE QUALITY of major surgery as performed in small hospitals.

PMID- 15436150
TI  - TRENDS in hospital dental service will affect the buying operation.

PMID- 15436151
TI  - Kitchen to patient--a straight line is the shortest distance.

PMID- 15436152
TI  - MASTER menus for September.

PMID- 15436153
TI  - FIFTY-SECOND Annual Convention of the American Hospital Association, Atlantic
      City, 18-21 September 1950.

PMID- 15436154
TI  - When disaster struck, we were prepared.

PMID- 15436155
TI  - The operating room technician.

PMID- 15436156
TI  - Newton-Wellesley Hospital develops an outpatient ledger card for reporting
      services.

PMID- 15436158
TI  - Hospitals can benefit from a uniform accounting system.

PMID- 15436157
TI  - Furnishing a hospital through community determination.

PMID- 15436159
TI  - STUDY of cells by cytologic smears aids in diagnosis of cancer.

PMID- 15436160
TI  - A reorganization that paid off in greater buying efficiency.

PMID- 15436161
TI  - Planning the electrical system for later maintenance ease.

PMID- 15436162
TI  - Converting hard water into soft transforms waste into thrift.

PMID- 15436164
TI  - MASTER menus for October.

PMID- 15436163
TI  - Therapeutic diets can be made more acceptable to patients.

PMID- 15436165
TI  - [The criminal psyche].

PMID- 15436166
TI  - [Functional disorders of the physiologic system of the connective tissue due to
      roentgen rays and subsequent treatment with Bogomolets antireticular cytotoxic
      serum].

PMID- 15436167
TI  - [Hydrogen sulfide poisoning].

PMID- 15436168
TI  - [Urovesical spasms].

PMID- 15436170
TI  - [Problem of tuberculosis in the Federal District of Rio de Janeiro].

PMID- 15436169
TI  - [The Internation Children's Emergency Fund].

PMID- 15436171
TI  - [Is the problem of gastroduodenal ulcer of a surgical nature?].

PMID- 15436172
TI  - [So-called aniline dyes and their hygienic importance].

PMID- 15436173
TI  - [Technical language].

PMID- 15436174
TI  - [Note on Hippocrates].

PMID- 15436175
TI  - [Reactive states caused by spiritualism].

PMID- 15436176
TI  - [Medico-social assistance in France].

PMID- 15436177
TI  - Some aspects of pulmonary resection.

PMID- 15436178
TI  - Chronic hyperplastic ileo-caecal tuberculosis.

PMID- 15436179
TI  - Volvulus of the small intestine.

PMID- 15436180
TI  - Neurotripsy and rehabilitation in poliomyelitis.

PMID- 15436181
TI  - Subtotal nephrectomy.

PMID- 15436182
TI  - Advances in orthopaedic surgery.

PMID- 15436183
TI  - Melanoma of the rectum.

PMID- 15436184
TI  - THIRTY-SEVENTH Conference of the All India Medical Licentiates' Association,
      Vellore, 20-22 April 1950.

PMID- 15436185
TI  - GENERAL Motors Medical Conference, La Grange, Illinois, April 24, 1950.

PMID- 15436186
TI  - The experience of General Motors in developing new techniques for selection,
      placement and follow-up of employees; a panel discussion.

PMID- 15436187
TI  - Antihistamine chemicals in the treatment of the common cold; report on a twenty
      seven month study.

PMID- 15436188
TI  - Accident proneness; a serious industrial problem. What can the industrial
      physician do about it?

PMID- 15436189
TI  - Adaptation of intravenous procaine to industrial medicine.

PMID- 15436190
TI  - INSTRUMENTS and devices displayed at General Motors Medical Conference, April 24,
      1950.

PMID- 15436191
TI  - The present position and future of British industrial medicine.

PMID- 15436193
TI  - Paracelsus: the 1950 Ramazzini Oration.

PMID- 15436192
TI  - THE Immortals; the Fifth Ramazzini Rendezvous, June 22-24, 1950.

PMID- 15436194
TI  - The relationship between truck and tractor driving and disorders of the spine and
      supporting structures; report of a survey.

PMID- 15436195
TI  - A controlled industrial study of an analgesic compound, edrisal with codeine.

PMID- 15436196
TI  - [Reflexotherapy by the use of mustard plasters on the hepato-reno-splenic
      dermatomes; its applications in dental and medical practice].

PMID- 15436197
TI  - [Reflexotherapy by the use of mustard plasters on the hepato-reno-splenic
      dermatomes; its applications in dental and medical practice].

PMID- 15436198
TI  - Hernias of the supravesical, inguinal, and lateral pelvic fossae: their
      diagnosis, classification, and relationship.

PMID- 15436199
TI  - Effect of splenic function and splenic disease on female physiology, with a brief
      analysis of 182 gestations after splenectomy.

PMID- 15436201
TI  - The life of the red blood cell.

PMID- 15436200
TI  - Synthetic oestrogens in treatment; with special reference to malignant disease.

PMID- 15436202
TI  - Clinical aspects of chloromycetin.

PMID- 15436203
TI  - Allergy in two stages; the full allergic responses resulting from two part
      allergens.

PMID- 15436204
TI  - Acute nephritis: a clinical study.

PMID- 15436205
TI  - Treatment of varicose veins in pregnancy; a critical survey of injection
      treatment based on 600 cases treated at the Rotunda Hospital.

PMID- 15436206
TI  - Chronic sinusitis in children.

PMID- 15436208
TI  - The lost art of malingering.

PMID- 15436207
TI  - Gravitational ulcers of the leg.

PMID- 15436209
TI  - Origins and distributions of blood groups.

PMID- 15436210
TI  - Crystalline cholesterol effusion of the pleural space.

PMID- 15436211
TI  - Second preface to volume 41 of Isis; notes on the reviewing of learned books.

PMID- 15436212
TI  - The first psychological laboratory.

PMID- 15436213
TI  - Benjamin Franklin and Jonathan Edwards on lightning and earthquakes.

PMID- 15436214
TI  - Was this the fate of the library of Alexander von Humboldt?

PMID- 15436215
TI  - Antoine Lavoisier's Traite Elementaire de Chimie; a bibliographical note.

PMID- 15436216
TI  - Samuel Hoole, translator of Leeuwenhoek's Select Works; with notes on that
      publication.

PMID- 15436217
TI  - A fifteenth-century planetary computer: al-Kashi's "Tabaq al-Manateq". Motion of
      the sun and moon in longitude.

PMID- 15436218
TI  - The astronomical instruments of Cha-ma-lu-ting, their identification, and their
      relations to the instruments of the observatory of Maragha.

PMID- 15436219
TI  - [Investigation of the relation of human undulant fever and brucellosis in
      domestic animals in Bulgaria].

PMID- 15436220
TI  - [Types of Mycobacterium tuberculosis in skin and other forms of human
      tuberculosis in Bulgaria].

PMID- 15436221
TI  - [Investigations of the opsonic and bacteriotropic effect of the swine erysipelas
      antiserum].

PMID- 15436222
TI  - [Paratuberculosis (Johne's disease) in cattle in Bulgaria].

PMID- 15436223
TI  - [Effect in vitro of certain sulfonamide and antibiotic preparations on the
      intestinal flora].

PMID- 15436224
TI  - [Study of leguminous nodule bacteria with the purpose of increasing the bean
      crop].

PMID- 15436225
TI  - [Experiments in obtaining pectinase from microorganisms for the purpose of
      increasing the transparency of fruit juices].

PMID- 15436226
TI  - [Method of hemagglutination by colored antigen in the rapid diagnosis of
      brucellosis].

PMID- 15436227
TI  - [Tuberculosis and infection with tuberculosis of Chairina moschata].

PMID- 15436228
TI  - [Cutaneous sporotrichosis].

PMID- 15436229
TI  - [Case of histoplasmosis in Bulgaria].

PMID- 15436230
TI  - [Pulmonary aspergillosis].

PMID- 15436231
TI  - [Case of acute and fatal moniliasis].

PMID- 15436232
TI  - [Onychomycosis penicillica in a woman].

PMID- 15436233
TI  - [Determination of fowl plague virus in the different parts of an infected
      incubated egg].

PMID- 15436234
TI  - [Phosphatase system in Penicillium crustosum 1/3 E..].

PMID- 15436235
TI  - [Muco-cutaneous diseases and the Geres treatment].

PMID- 15436236
TI  - [Medicine and music; Albert Schweitzer].

PMID- 15436237
TI  - [Prophylaxis of tuberculosis with BCG; a campaign in action].

PMID- 15436239
TI  - [Obligatory declaration of communicable diseases].

PMID- 15436238
TI  - [Medicine and euthanasia].

PMID- 15436240
TI  - [The Escola Medico-Cirurgica of Goa pays homage to Professor Egas Moniz].

PMID- 15436241
TI  - Comparison of the utilization of certain sugars by some oral actinomycetes and
      lactobacilli.

PMID- 15436242
TI  - A comparison of surveys on the cause of dental caries.

PMID- 15436243
TI  - The demands which have brought about our modern public health movement.

PMID- 15436244
TI  - Public health dentistry in Tennessee.

PMID- 15436245
TI  - Mississippi mouth health program.

PMID- 15436246
TI  - Public health dentistry in Arkansas.

PMID- 15436247
TI  - Public health dentistry at the University of Tennessee; the present and future.

PMID- 15436248
TI  - My name is "preventable disease.".

PMID- 15436249
TI  - The dentist and the dental health program.

PMID- 15436250
TI  - Report on the study of dental public health services in New Zealand.

PMID- 15436251
TI  - Principles of cavity preparation in crown and bridge prosthesis; the full crown.

PMID- 15436252
TI  - Indications and the diagnosis for fixed partial denture prosthesis.

PMID- 15436253
TI  - Antibiotics in the treatment of yeastlike infections of the root canal.

PMID- 15436254
TI  - Elements of diagnosis leading to full or partial dentures.

PMID- 15436255
TI  - Fixed-movable partial dentures with interlocking onlay attachments: review of a
      practical case.

PMID- 15436256
TI  - Surgical treatment of early localized osteitis.

PMID- 15436257
TI  - Cyst on a nonvital incisor.

PMID- 15436258
TI  - THE DENTAL laboratory issue the first imperative step.

PMID- 15436259
TI  - Nineteen fifty survey of the dental profession; the dentist and certain aspects
      of his training and practice.

PMID- 15436260
TI  - Dietary consultation--a service for small institutions; scope of work.

PMID- 15436261
TI  - Nutritional adequacy, cost, and acceptability of lunches in an Iowa school lunch
      program.

PMID- 15436262
TI  - Is the dietitian adequately prepared to teach?

PMID- 15436263
TI  - Anti-peptic ulcer dietary factor (vitamin "U") in the treatment of peptic ulcer.

PMID- 15436264
TI  - Dental caries in Norwegian children during and after the second world war.

PMID- 15436265
TI  - Nutritional status of children; food intakes and biochemical and medical
      evaluations of adolescent boys.

PMID- 15436266
TI  - A Cheechako dietary consultant.

PMID- 15436267
TI  - Synthesis in medicine with special reference to homeopathy.

PMID- 15436268
TI  - A laboratory study of twenty drugs on normal human beings with comments on their
      symptomatology and therapeutic use.

PMID- 15436269
TI  - Modern concepts in obstetrics.

PMID- 15436270
TI  - Rheumatic fever: public health aspects.

PMID- 15436271
TI  - Case histories: homeopathy in cancer.

PMID- 15436272
TI  - Clinical notes from Timothy Field Allen, M.D.

PMID- 15436273
TI  - Homeopathic treatment of hypertension.

PMID- 15436274
TI  - Homeopathy in modern medicine.

PMID- 15436275
TI  - Low back pain: psychosomatic viewpoint.

PMID- 15436276
TI  - The diagnosis of liver disease.

PMID- 15436278
TI  - Homeopathic pharmacy.

PMID- 15436277
TI  - A laboratory study of twenty drugs on normal human beings with comments on their
      symptomatology and therapeutic use.

PMID- 15436279
TI  - Clinical notes from Timothy Field Allen, M. D.

PMID- 15436280
TI  - Evaluation of cytologic diagnosis of lung cancer.

PMID- 15436281
TI  - A clinical evaluation of certain antihistaminic and antispasmodic drugs in
      Parkinson's disease.

PMID- 15436282
TI  - Congenital pulmonary stenosis with intact ventricular septum.

PMID- 15436283
TI  - Acute primary Klebsiella pneumonia.

PMID- 15436284
TI  - Pulmonary metastatic lesion successfully treated with radioactive iodine; report
      of a case of pulmonary metatasis from a papillary adenocarcinoma of the thyroid.

PMID- 15436285
TI  - Primary carcinoma of the nail.

PMID- 15436286
TI  - Aureomycin hydrochloride in actinomycosis.

PMID- 15436287
TI  - Strangulated diaphragmatic hernia complicating delivery.

PMID- 15436288
TI  - STANDARDS of effective administration of inhalational therapy.

PMID- 15436289
TI  - Deficiencies of the fat-soluble vitamins.

PMID- 15436290
TI  - MASSAGE: use of electric vibrator not practice of massage.

PMID- 15436291
TI  - MALPRACTICE: resident's liability for negligence during operation.

PMID- 15436292
TI  - ADMISSIBILITY in evidence of results of chemical tests for intoxication.

PMID- 15436293
TI  - Severe, sporadic virus pneumonias; diagnostic and therapeutic problems.

PMID- 15436294
TI  - Diabetic coma.

PMID- 15436295
TI  - Clinical study of prevention of erythroblastosis with Rh hapten.

PMID- 15436296
TI  - Tuberculous meningitis.

PMID- 15436297
TI  - Thromboembolism associated with auricular fibrillation; continuous anticoagulant
      therapy.

PMID- 15436298
TI  - Cor triloculare biatrium.

PMID- 15436299
TI  - TELEX Hearing aid, model 200, accepted.

PMID- 15436300
TI  - Cleartone hearing aids, model 500 and Regency model, accepted.

PMID- 15436302
TI  - Midwest all-metal humidifier, model 100, accepted.

PMID- 15436301
TI  - Croupette humidity and oxygen tent accepted.

PMID- 15436303
TI  - Pharmacology and toxicology of certain organic phosphorus insecticides; general
      description of their activity and usefulness; pharmacology; toxicology; clinical
      experience; effects on beneficial forms of life, crops and soil and residue
      hazards.

PMID- 15436304
TI  - Medical education in the United States and Canada; fiftieth annual report on
      medical education in the United States and Canada by the Council on Medical
      Education and Hospitals of the American Medical Association.

PMID- 15436305
TI  - RIGHT of undertaker to give opinion as to cause of death.

PMID- 15436306
TI  - HOSPITALS in general; liability for death of patient following blood transfusion.

PMID- 15436307
TI  - The transitory superficial granular layer of the cerebellar cortex; its
      relationship to certain cerebellar neoplasms.

PMID- 15436308
TI  - Office management of some common types of headaches.

PMID- 15436309
TI  - The erythrocyte sedimentation rate in normal pregnancy and puerperium;
      preliminary report and evaluation.

PMID- 15436310
TI  - Granuloma inguinale treated by vulvectomy and streptomycin; report of four cases.

PMID- 15436311
TI  - Typhoid fever in a child treated with chloromycetin; case report.

PMID- 15436312
TI  - Graduate medical education at Woman's Medical College of Pennsylvania.

PMID- 15436313
TI  - Women in American medicine.

PMID- 15436314
TI  - An approach to the mastitis problem.

PMID- 15436315
TI  - Tibial fracture in an aged stallion.

PMID- 15436316
TI  - A new method of permanent intramedullary pinning.

PMID- 15436317
TI  - Recurrent iridocyclitis (periodic ophthalmia) of horses; agglutination and lysis
      of leptospiras by serums deriving from horses affected with recurrent
      iridocyclitis.

PMID- 15436318
TI  - Infectious equine encephalomyelitis in the United States in 1949.

PMID- 15436319
TI  - Blackleg in deer.

PMID- 15436320
TI  - Guinea-worm (Dracunculus insignis, Leidy 1858) infection in a dog.

PMID- 15436321
TI  - Apomorphine in dogs.

PMID- 15436322
TI  - Phthalylsulfacetamide (thalamyd) in veterinary medicine.

PMID- 15436323
TI  - Malignant melanoma of the oral mucosa in a dog.

PMID- 15436324
TI  - Coccidiosis in the dog--clinical observations.

PMID- 15436325
TI  - Distribution of Newcastle disease virus in, and elimination from, intratracheally
      and intramuscularly inoculated birds.

PMID- 15436326
TI  - RECOMMENDED nutrient allowances for sheep.

PMID- 15436327
TI  - WARD Giltner, D.V.M., M.S., Dr. P.H., 1882-1950.

PMID- 15436328
TI  - On the prenatal growth of the mammary gland rudiment in the mouse.

PMID- 15436329
TI  - Comparison of fracture repair in the frog, lizard and rat.

PMID- 15436330
TI  - Effect of malnutrition as compared with hypophysectomy on organ weight of the
      albino rat.

PMID- 15436331
TI  - The gradient of mucosal surface area in the small intestine of the rat.

PMID- 15436332
TI  - The intramural blood supply of the upper jejunum in man.

PMID- 15436333
TI  - The development in vitro of the submandibular and sublingual glands of Mus
      musculus.

PMID- 15436334
TI  - Explantation experiments on the influence of the connective tissue capsule on the
      development of the epithelial part of the submandibular gland of Mus musculus.

PMID- 15436335
TI  - The fate of the nerves of the deciduous teeth.

PMID- 15436336
TI  - Compression of complete diets for horses.

PMID- 15436337
TI  - Motility patterns of the cecum of the horse.

PMID- 15436338
TI  - The incidence of female genital abnormalities in swine.

PMID- 15436339
TI  - The effect of season of birth on sexual development in gilts.

PMID- 15436340
TI  - The effect of adding APF supplements and concentrates containing supplementary
      growth factors to a corn-soybean oil meal ration for weanling pigs.

PMID- 15436341
TI  - Comparisons of pastures and supplements for growing-fattening pigs.

PMID- 15436342
TI  - Sodium, chlorine, and potassium requirements of growing pigs.

PMID- 15436343
TI  - The relation of the post-partum breeding interval to reproductive efficiency in
      the dairy cow.

PMID- 15436344
TI  - The effect of sulfaquinoxaline administration on metabolism of vitamin A and
      carotene and on hemoglobin young dairy calves.

PMID- 15436345
TI  - The effects of stilbestrol, testosterone, thyroid alteration and spaying on the
      growth and fattening of beef heifers.

PMID- 15436346
TI  - Influence of shows on productive values in beef cattle.

PMID- 15436347
TI  - The extension of record of performance in beef cattle.

PMID- 15436349
TI  - The tenderness of beef in relation to different muscles and age in the animal.

PMID- 15436348
TI  - A study of some of the factors influencing the birth and weaning weights of beef
      calves.

PMID- 15436350
TI  - Some relationships between chemical composition, nutritive value, and intake of
      forages grazed by steers and weathers.

PMID- 15436351
TI  - The relative nutritive value of Kentucky bluegrass, timothy, brome grass, orchard
      grass, and alfalfa.

PMID- 15436352
TI  - The value of average digestibility data.

PMID- 15436353
TI  - Effect of stilbestrol on the growth rate of suckling lambs.

PMID- 15436354
TI  - The effect of stilbestrol on fattening lambs.

PMID- 15436355
TI  - Physiological effects of thiouracil and similar drugs on sheep.

PMID- 15436356
TI  - A study of the function of cobalt in the nutrition of sheep.

PMID- 15436357
TI  - The effect of cobalt on the synthesis of vitamin B12 in the rumen of sheep.

PMID- 15436358
TI  - Riboflavin deficiency in the lamb.

PMID- 15436359
TI  - The minimum phosphorus requirement of lambs for phosphorus equilibrium.

PMID- 15436360
TI  - The effect of feeding concentrates to range ewes on lamb and wool productivity.

PMID- 15436361
TI  - Effect of vitamin A supplementation on reproduction of ewes grazed on green and
      dry summer ranges.

PMID- 15436362
TI  - Physiological responses of man to inspiration of hypoxic oxygen-nitrogen mixture.

PMID- 15436363
TI  - Mechanics of breathing in man.

PMID- 15436364
TI  - Individual differences in vascular responses and their relationship to cold
      tolerance.

PMID- 15436365
TI  - Occurrence in normal individuals of diurnal variations in acuity of the sense of
      taste for sucrose.

PMID- 15436366
TI  - Phreno-vagal anastomosis in the dog.

PMID- 15436367
TI  - In vivo measurement of body fat and body water in a group of normal men.

PMID- 15436368
TI  - Heat production and energy requirements of tropical people.

PMID- 15436369
TI  - Effect of skin temperature on salt concentration of sweat.

PMID- 15436370
TI  - Relation of maximum grip strength to grip strength endurance.

PMID- 15436371
TI  - Response of human and canine gall bladder to cholecystokinin.

PMID- 15436372
TI  - Character of blood flow in the vasodilated finger.

PMID- 15436373
TI  - The adequacy of employee selection reports.

PMID- 15436374
TI  - Cross validation of an abbreviated point job evaluation system.

PMID- 15436375
TI  - Age and route sales efficiency.

PMID- 15436376
TI  - Ortho-Rater norms and sex differences.

PMID- 15436377
TI  - Fluorescent light versus daylight.

PMID- 15436378
TI  - Inconsistency in the predictive value of a battery of tests.

PMID- 15436379
TI  - Intercorrelations in merit rating traits.

PMID- 15436380
TI  - How readable are corporate annual reports?

PMID- 15436381
TI  - Rorschach responses, Strong blank scales, and job satisfaction among policemen.

PMID- 15436382
TI  - Card versus booklet forms of the MMPI.

PMID- 15436383
TI  - A factor analysis of MMPI and aptitude test data.

PMID- 15436384
TI  - A combined oral reading and psychogalvanic response technique for investigating
      certain reading abilities of college students.

PMID- 15436385
TI  - Geographical sampling in testing the appeal of radio broadcasts.

PMID- 15436386
TI  - The effect of color in direct mail advertising.

PMID- 15436387
TI  - Brand discrimination among cigarette smokers.

PMID- 15436388
TI  - Catarrhal otitis media with effusion.

PMID- 15436389
TI  - The use of physostigmine in the treatment of the black widow spider bite.

PMID- 15436390
TI  - Some physiological findings on normal men subjected to negative g.

PMID- 15436391
TI  - Effects of positive acceleration on pilots in flight with a comparison of the
      responses of pilots and passengers in an airplane and subjects on a human
      centrifuge.

PMID- 15436392
TI  - Effect of various drugs on psychomotor performance at ground level and at
      simulated altitudes of 18,000 feet in a low pressure chamber.

PMID- 15436393
TI  - High altitude high velocity flying with special reference to the human factors.
      II. Time of consciousness during exposure to various pressure altitudes.

PMID- 15436394
TI  - Physiological considerations regarding safety measures for sudden decompression
      in civil passenger aircraft.

PMID- 15436395
TI  - Some effects on auditory stimuli upon voice.

PMID- 15436396
TI  - Effect of carrot diet and restricted feeding on the resistance of the rat to
      hypoxia.

PMID- 15436397
TI  - Common cardiac conditions in the young male adult.

PMID- 15436398
TI  - Ultrasonics in clinical medicine.

PMID- 15436399
TI  - Regional Medical Examiners Conference.

PMID- 15436400
TI  - Civil aviation and public health.

PMID- 15436401
TI  - An iron-oxidizing bacterium from the acid drainage of some bituminous coal mines.

PMID- 15436402
TI  - Experiments on photoreactivation of bacteriophages inactivated with ultraviolet
      radiation.

PMID- 15436403
TI  - The occurrence of anaerobic gram-negative diplococci in the normal human mouth.

PMID- 15436404
TI  - A new staining technique for polar bodies.

PMID- 15436405
TI  - The utilization of some organic compounds by one strain each of Salmonella
      anatum, Salmonella oranienburg, and Salmonella pullorum.

PMID- 15436406
TI  - The effect of 2,4-dinitrophenol and phage T2 on Escherichia coli B.

PMID- 15436407
TI  - The stimulation of gene recombination in Escherichia coli.

PMID- 15436408
TI  - Partial purification and resolution of acetoacetic decarboxylase.

PMID- 15436409
TI  - Glucose metabolism of Clostridium perfringens: existence of metallo-aldolase.

PMID- 15436410
TI  - The germicidal and sporicidal efficacy of methyl bromide for Bacillus anthracis.

PMID- 15436411
TI  - Identification of the Koch-Weeks bacillus (Hemophilus aegyptius).

PMID- 15436412
TI  - Hemagglutination by the Koch-Weeks bacillus (Hemophilus aegyptius).

PMID- 15436413
TI  - A method for the determination of the thermal resistance of bacterial spores.

PMID- 15436414
TI  - A biotin function in succinic acid decarboxylation by Propionibacterium
      pentosaceum.

PMID- 15436415
TI  - The use of potassium tellurite, sodium azide, and acetic acid in a selective
      medium for the isolation of Listeria monocytogenes.

PMID- 15436416
TI  - A motile Lactobacillus from the cecal feces of turkeys.

PMID- 15436417
TI  - The propagation of Borrelia anserina in embryonated eggs employing the yolk sac
      technique.

PMID- 15436418
TI  - The effect of monochromatic ultraviolet radiation on the infectivity and
      hemagglutinating ability of the influenza virus type A strain PR-8.

PMID- 15436419
TI  - Antisporulation factors in complex organic media. I. Growth and sporulation
      studies on Bacillus larvae.

PMID- 15436420
TI  - The influence of antibiotics and sulfa drugs on Bacillus larvae, cause of
      American foulbrood of the honeybee, in vitro and in vivo.

PMID- 15436421
TI  - Yeasts from Hawaiian fruit flies: their identification and ability to produce
      riboflavin.

PMID- 15436422
TI  - The biological degradation of soluble cellulose derivatives and its relationship
      to the mechanism of cellulose hydrolysis.

PMID- 15436423
TI  - Acetic acid oxidation by Escherichia coli and Aerobacter aerogenes.

PMID- 15436424
TI  - The influence of certain salts, amino acids, sugars, and proteins on the
      stability of rickettsiae.

PMID- 15436425
TI  - The production of streptocin by different strains of Streptomyces griseus.

PMID- 15436426
TI  - The bacterial oxidation of aromatic compounds. IV. Studies on the mechanism of
      enzymatic degradation of protocatechuic acid.

PMID- 15436427
TI  - The vitamin requirements for glycerol oxidation by Streptococcus faecalis.

PMID- 15436428
TI  - Immunization with heat-killed Mycobacterium paratuberculosis in mineral oil.

PMID- 15436429
TI  - A comparative study of known food-poisoning staphylococci and related varieties.

PMID- 15436430
TI  - Chromatin staining of bacteria during bacteriophage infection.

PMID- 15436431
TI  - Electron and light microscopic studies of bacterial nuclei. I. Adaptation of
      cytological processing to electron microscopy; bacterial nuclei as vesicular
      structures.

PMID- 15436432
TI  - Electron and light microscopic studies of bacterial nuclei. II. An improved
      standing technique for the nuclear chromatin of bacterial cells.

PMID- 15436433
TI  - Morphological studies in the genus Nocardia. II. Cytological studies.

PMID- 15436434
TI  - Cytological changes in Escherichia coli produced by infection with phage T2.

PMID- 15436435
TI  - A reaction of bacterial cells with formaldehyde.

PMID- 15436436
TI  - The effective concentrations of penicillin in vitro and in vivo for streptococci,
      pneumococci, and Treponema pallidum.

PMID- 15436437
TI  - The action of microorganisms on fats. I. Oxygen uptake by bacteria in the
      presence of lipid substrates.

PMID- 15436438
TI  - The metabolism of glucose by Ashbya gossypii.

PMID- 15436439
TI  - The chemotherapy of experimental tuberculosis. I. The in vitro activity of
      thiosemicarbazides, thiosemicarbazones, and related compounds.

PMID- 15436440
TI  - The chemotherapy of experimental tuberculosis. II. Thiosemicarbazones and
      analogues in experimental tuberculosis in the mouse.

PMID- 15436441
TI  - The inhibition of bacteriophagy by bacterial and nonbacterial polysaccharides.

PMID- 15436442
TI  - A urease test for the differentiation of Brucella suis.

PMID- 15436443
TI  - Studies on the metabolism of photosynthetic bacteria. VI. Metabolism of
      isopropanol by a new strain of Rhodopseudomonas gelatinosa.

PMID- 15436444
TI  - A new bacterium (Hemophilus piscium n. sp.) from ulcer disease of trout.

PMID- 15436445
TI  - A turbidimetric method for the assay of antibiotics.

PMID- 15436446
TI  - The physiological characters of Bacillus coagulans (Bacillus thermoacidurans).

PMID- 15436447
TI  - Desoxyribosides and vitamin B12 as growth factors for lactic acid bacteria.

PMID- 15436448
TI  - The mutation of Pseudomonas putrefaciens to glucose utilization and its enzymatic
      basis.

PMID- 15436449
TI  - Studies on the disappearance of folic acid from bacterial cells.

PMID- 15436450
TI  - The transformation of typhoid bacilli into L forms under various conditions.

PMID- 15436451
TI  - The properties of L forms isolated from Salmonella and the isolation of L forms
      from Shigella.

PMID- 15436452
TI  - The nutrition of Brucellae: utilization of single amino acids for growth.

PMID- 15436453
TI  - The relation of ion antagonism to the inorganic nutrition of lactic acid
      bacteria.

PMID- 15436454
TI  - Arthur Parker Hitchens, 1877-1949.

PMID- 15436455
TI  - The growth of the Reiter strain of Treponema pallidum in the chick embryo.

PMID- 15436456
TI  - Factors necessary for maximum growth of Clostridium bifermentans.

PMID- 15436457
TI  - Mutants of Escherichia coli requiring methionine or vitamin B12.

PMID- 15436458
TI  - Observations on the multiplication of phages affecting Streptomyces griseus.

PMID- 15436459
TI  - Biotin and arginine replacements in the nutrition of Clostridium sporogenes.

PMID- 15436460
TI  - Some additional nutritional requirements of certain lactic acid bacteria.

PMID- 15436461
TI  - Nutritional requirements of Treponemata. II. Pantothenic acid, glutamine, and
      phenylalanine as additional growth-promoting factors for the Reiter treponeme.

PMID- 15436462
TI  - The effect of virus infection on the utilization of tryptophan by Escherichia
      coli.

PMID- 15436463
TI  - Demonstration of the chromatinic bodies of Escherichia coli and Proteus vulgaris
      with the aid of the phase contrast microscope.

PMID- 15436464
TI  - Synthesis of glutamic acid and glutamyl polypeptide by Bacillus anthracis. I.
      Formation of glutamic acid by transamination.

PMID- 15436465
TI  - A new Salmonella type: Salmonella haifa.

PMID- 15436466
TI  - Phenol production by coliform bacteria.

PMID- 15436467
TI  - The production of "giant" cells of Pasteurella pestis by treatment with camphor.

PMID- 15436468
TI  - Control of mold contaminants on solid media by the use of actidione.

PMID- 15436469
TI  - Some factors affecting the potencies of vitamin B12 and Leuconostoc citrovorum
      factor of certain natural products.

PMID- 15436470
TI  - The true nature of the stimulation of the growth of Lactobacillus arabinosus 17-5
      by folic acid.

PMID- 15436471
TI  - Failure of folic acid to antagonize sulfanilamide non-competitively in the growth
      of Lactobacillus arabinosus 17-5.

PMID- 15436472
TI  - Determination of molecular weights of proteins in spread monolayers.

PMID- 15436473
TI  - The role of glutamic acid in arginine synthesis by Lactobacillus arabinosus.

PMID- 15436474
TI  - Electron microscopy of crystalline edestin.

PMID- 15436475
TI  - Oxidation in vivo of the methyl groups of choline, betaine, dimethylthetin, and
      dimethyl-beta-propiothetin.

PMID- 15436476
TI  - On the origin of certain serum peptidases as indicated by experimental hemolytic
      anemia in dogs.

PMID- 15436477
TI  - The conversion of N15-containig indole to niacin by niacin-requiring strain 39401
      of Neurospora.

PMID- 15436478
TI  - Preparation and characterization of the enzyme which converts testosterone to
      androstenedione.

PMID- 15436479
TI  - Assay of insulin in vitro by fibril elongation and precipitation.

PMID- 15436480
TI  - Studies on natural and racemic amino acids with rats.

PMID- 15436481
TI  - The location in protoporphyrin of the carbon atoms derived from the alpha-carbon
      atom of glycine.

PMID- 15436482
TI  - The formation of ketone bodies from isovaleric acid.

PMID- 15436483
TI  - The utilization of isovaleric acid for the synthesis of cholesterol.

PMID- 15436484
TI  - An improved method for the preparation of protective pseudoglobulin.

PMID- 15436485
TI  - The reductive cleavage of 4-dimethylaminoazobenzene by rat liver: reactivation of
      carbon dioxide-treated homogenates by riboflavin-adenine dinucleotide.

PMID- 15436486
TI  - Some protein changes in fluids of the developing chicken embryo.

PMID- 15436487
TI  - The titratable groups of ribonucleic acid from yeast and of certain fractions
      derived by the action of ribonuclease.

PMID- 15436488
TI  - Influence of thyroid activity on exchange of liver adenosine triphosphate
      phosphorus.

PMID- 15436489
TI  - Biochemical stability of the methyl group of creatine and creatinine.

PMID- 15436490
TI  - Oxidation of isotopic palmitic acid in animal tissues.

PMID- 15436491
TI  - A quantitative color reaction for cortisone and related 17,21-dihydroxy-20
      ketosteroids.

PMID- 15436492
TI  - Mode of inhibition of chymotrypsin by diisopropyl fluorophosphate. II.
      Introduction of isopropyl and elimination of fluorine as hydrogen fluoride.

PMID- 15436493
TI  - Relations between insulin and pituitary hormones in amino acid metabolism.

PMID- 15436494
TI  - Spectrophotometric studies. XV. Hydration of macro sized crystals of human
      hemoglobin, and osmotic concentrations in red cells.

PMID- 15436495
TI  - Size and density of polystyrene particles measure by ultracentrifugation.

PMID- 15436496
TI  - The separation of natural estrogens by countercurrent distribution.

PMID- 15436497
TI  - Use of borax to lake blood for oxygen determination.

PMID- 15436498
TI  - The preparation of beta-dihydroequilin.

PMID- 15436499
TI  - On the origin of the carbon chain of cysteine in the rat.

PMID- 15436500
TI  - The products of oxidation of fatty acids by isolated rat liver mitochondria.

PMID- 15436501
TI  - The failure of acetyldehydrotryptophan to support the growth of the rat.

PMID- 15436502
TI  - A study of non-competitive antagonism with chloromycetin and related analogues of
      phenylalanine.

PMID- 15436503
TI  - Anti-fatty liver activity of crystalline trypsin in insulin-treated
      depancreatized dogs.

PMID- 15436504
TI  - Chemical analysis of the T7 bacteriophage of Escherichia coli.

PMID- 15436505
TI  - The inactivation of invertase by tyrosinase. I. The influence of certain phenolic
      compounds on the inactivation.

PMID- 15436506
TI  - Concentration of bound pantothenic acid.

PMID- 15436507
TI  - A color test for fructose.

PMID- 15436508
TI  - Cholesterol esterases. III. Occurrence and characteristics of cholesterol
      esterase of serum.

PMID- 15436509
TI  - The nitrogenous constituents of the tissus lipides. III. The effect of acute
      choline deficiency on the tissue lipides of young puppies.

PMID- 15436510
TI  - Lipolytic activity of adipose tissue in man and rat.

PMID- 15436511
TI  - Immunochemical studies of beta-lactoglobulin.

PMID- 15436512
TI  - Dissociation constants of radium-organic acid complexes measured by ion exchange.

PMID- 15436513
TI  - Some biological and chemical properties of the citrovorum factor.

PMID- 15436514
TI  - Thermal coagulation of serum proteins. III. The effects of pH and of sulfhydryl
      reagents on the nature of the coagulum.

PMID- 15436515
TI  - On the role of 2,6-diaminopurine in the biosynthesis of nucleic acid guanine.

PMID- 15436516
TI  - A study of the metabolism of 2,4-diaminopyrimidine.

PMID- 15436517
TI  - A new synthesis of the purines adenine, hypoxanthine, xanthine, and isoguanine.

PMID- 15436518
TI  - The metabolism of acetone. I. Gross aspects of catabolism and excretion.

PMID- 15436519
TI  - New frontiers in education.

PMID- 15436521
TI  - [Dental caries: etiology, mechanism, prevention].

PMID- 15436520
TI  - The control and elimination of pain in dental procedures.

PMID- 15436522
TI  - Would health insurance involve me?

PMID- 15436523
TI  - Cysts of the mandible.

PMID- 15436524
TI  - NATIONAL broadcast on dentistry by the Canadian Broadcasting Corporation.

PMID- 15436525
TI  - [Dental caries; etiology, mechanism and prevention].

PMID- 15436526
TI  - [What are you doing for your young patients?].

PMID- 15436527
TI  - [Why accuse the others?].

PMID- 15436528
TI  - Some present problems in the genetic effects of radiation.

PMID- 15436529
TI  - The effect of x-rays on chromosome structure.

PMID- 15436530
TI  - Chromosomal interchanges induced in tradescantia microspores by fast neutrons
      from uranium fission.

PMID- 15436531
TI  - Effects of radiation on mitosis.

PMID- 15436532
TI  - Cytological and phenotypical effects induced in maize by x-rays and the Bikini
      Test Able atomic bomb.

PMID- 15436533
TI  - Effects of radiation on fungi.

PMID- 15436534
TI  - Some effects of ultraviolet irradiation on microorganisms.

PMID- 15436535
TI  - Radiation induced mutations in chemical requirements in Salmonella typhimurium.

PMID- 15436536
TI  - The effect of radiations on genetic mechanisms of Paramecium aurelia.

PMID- 15436537
TI  - Inactivation of enzyme-substrate film by small doses of x-rays.

PMID- 15436538
TI  - Discussion of population genetics and radiation.

PMID- 15436539
TI  - Partial dominance in relation to the need for studying induced mutations
      individually.

PMID- 15436540
TI  - Properties of postganglionic B fibers.

PMID- 15436541
TI  - Properties of sympathetic B ganglion cells.

PMID- 15436542
TI  - Potential changes evoked in a curarized sympathetic ganglion by presynaptic
      volleys of impulses.

PMID- 15436543
TI  - Dual mechanism of synaptic transmission through a sympathetic ganglion.

PMID- 15436544
TI  - Refractoriness, facilitation and inhibition in a sympathetic ganglion.

PMID- 15436545
TI  - [Restoration of the long flexor tendon of the thumb without sacrificing the
      primary tendon].

PMID- 15436546
TI  - [Epibronchial diverticula of the esophagus].

PMID- 15436547
TI  - [Lymphadeno-colpo-hysterectomy by abdominal approach].

PMID- 15436548
TI  - Cotton sutures and ligatures; observations on 3,000 cases at the Clara Swain
      Hospital.

PMID- 15436550
TI  - Treatment of burns.

PMID- 15436549
TI  - Anesthesia at the Clara Swain Hospital, with notes on a disposable ether mask of
      high efficiency; technic and results 1941-49.

PMID- 15436551
TI  - Placenta praevia, 1939-1948.

PMID- 15436552
TI  - The sterilization of Hydnocar pus and other oils.

PMID- 15436553
TI  - The vaginal smear as a diagnostic and prognostic aid in abortion.

PMID- 15436554
TI  - Radioactive iodine uptake in the hypermetabolism of acromegaly.

PMID- 15436555
TI  - A comparison of androgens determined biologically and 17-ketosteroids determined
      chemically in urine (normal and abnormal).

PMID- 15436556
TI  - Congenital adrenal hyperplasia with pseudohermaphrodism and symptoms of Addison's
      disease; clinical course following bilateral total adrenalectomy, with metabolic
      studies, pathologic findings and discussion of etiology.

PMID- 15436557
TI  - The influence of bilateral prefrontal lobotomy on thyroid activity in psychiatric
      patients.

PMID- 15436558
TI  - The association of congenital spastic quadriplegia and androgenic precocity in
      four patients.

PMID- 15436559
TI  - Idiopathic lactation following thoracoplasty.

PMID- 15436560
TI  - The clinical significance of the blood iodine; a review.

PMID- 15436561
TI  - The effect of adrenocorticotropic hormone (corticotropin) on the muscular
      performance of hypophysectomized rats.

PMID- 15436562
TI  - Clinical experiences with adrenocorticotropic hormone (cortrophin) in a patient
      with chronic rheumatoid arthritis and in a patient with Sheehan's syndrome.

PMID- 15436563
TI  - Preliminary experiences with cortrophin in rheumatoid arthritis in children.

PMID- 15436564
TI  - Clinical administration of corticotropic hormone in the therapy of rheumatoid
      arthritis.

PMID- 15436565
TI  - Observations in a patient with chronic nephritis with nephrotic syndrome, during
      administration of corticotropic hormone.

PMID- 15436566
TI  - Some preliminary observations on the treatment of rheumatoid arthritis with
      cortisone plus insulin.

PMID- 15436567
TI  - The effect of hypophysectomy and growth hormone on phosphorus metabolism.

PMID- 15436568
TI  - Studies on the effects of hypophysectomy and of growth and adrenocorticotropic
      hormones on certain phosphorous fractions in the rat liver.

PMID- 15436569
TI  - The effect of growth hormone on hepatic catalase, erythrocyte volume, and
      hemoglobin in rats.

PMID- 15436570
TI  - The effects of prolonged perfusion of the dog's pancreas with glucose.

PMID- 15436571
TI  - Action of steroids on cerebral metabolism.

PMID- 15436572
TI  - Hormonal factors affecting avidin secretion and biotin blood levels in the chick.

PMID- 15436573
TI  - A study of the metabolism of single therapeutic doses (2.0 mg.) of estrone in
      healthy women in the preovulatory and postovulatory phases of the menstrual
      cycle.

PMID- 15436574
TI  - A steroid which promotes tissue growth without concomitant genital activity.

PMID- 15436575
TI  - Factors in wheat germ oil affecting the sex organs of hypophysectomized rats.

PMID- 15436576
TI  - The use of progesterone in treatment of cancer of the prostate.

PMID- 15436577
TI  - Tracer studies with labeled preparations of anterior pituitary hormones: ACTH.

PMID- 15436578
TI  - Fate of intravenously administered adrenocorticotropic hormone (ACTH).

PMID- 15436579
TI  - The effect of ACTH upon the level of 17-hydroxycorticosterone in the adrenal vein
      blood of dogs.

PMID- 15436580
TI  - The functional relationship between the pituitary gland and the parathyroids.

PMID- 15436581
TI  - Radioiodine (I131) and gonadal function: an experimental and clinical study.

PMID- 15436582
TI  - Carrier-free radioactive iodine131 thyroid uptake and urinary excretion in normal
      and hypothyroid children.

PMID- 15436583
TI  - Uptake of radioactive iodine, I131, by the thyroid gland after administration of
      tracer doses.

PMID- 15436584
TI  - Observations on the relationship between bone marrow activity and thyroid
      function.

PMID- 15436585
TI  - Thyroxine-like activity of acrylic acid analogues of thyroxine.

PMID- 15436586
TI  - Clinical application of certain mercaptoimidazoles to hyperthyroidism.

PMID- 15436587
TI  - Thyroid hormone and tissue cholesterol distribution.

PMID- 15436588
TI  - Studies on hormonal control of serum lipid partition in man.

PMID- 15436589
TI  - The effects of ACTH, cortisone, and of other steroid compounds upon fat
      metabolism in diabetic and nondiabetic human subjects.

PMID- 15436590
TI  - The anabolic effect of testosterone compound as manifested by increased height
      and weight gain in boys.

PMID- 15436591
TI  - The effect of testosterone administration upon the human testis.

PMID- 15436592
TI  - Sex-linked growth retardation and juvenile diabetes mellitus.

PMID- 15436593
TI  - Pituitary infantilism; treatment with purified growth hormone, thyroid and
      sublingual methyl testosterone.

PMID- 15436594
TI  - Familial female pseudohermaphrodism.

PMID- 15436595
TI  - The effect on the linear growth, weight gain, and histologic pattern of the
      testes of young rats by large doses of DOCA, lipoadrenal cortex, thyroid,
      thyroxine, testosterone propionate and physiologic doses of testosterone
      propionate.

PMID- 15436596
TI  - The relation of adrenal activity to experimental hypertension.

PMID- 15436597
TI  - Interrelations between the adrenal cortex and lymphoid tissues: growth of adrenal
      transplants in spleen and thymus with local thymic atrophy.

PMID- 15436598
TI  - The effect of adrenal transplanting on the stress reaction to hypoxia.

PMID- 15436599
TI  - The use of cystine labeled with S35 as a tool for studying adrenal physiology and
      metabolism.

PMID- 15436600
TI  - Changes in responsiveness to insulin in diabetes mellitus induced by the
      administration of desoxycorticosterone.

PMID- 15436601
TI  - The metabolic effects of ACTH in a patient with Cushing's syndrome and
      acromegaly.

PMID- 15436602
TI  - Effect of adrenocorticotropic hormone (ACTH) on the pathologic changes induced by
      desoxycorticosterone acetate (DCA).

PMID- 15436603
TI  - The response of the adrenal cortex and thyroid gland to ACTH and cortisone in
      patients with hyperthyroidism and the nephrotic syndrome.

PMID- 15436604
TI  - The effect of small dosages of ACTH protein and ACTH peptides in cases of
      rheumatoid arthritis.

PMID- 15436605
TI  - Erythrocyte sedimentation rate in DCA and cortisone treated animals.

PMID- 15436606
TI  - Oral steroid administration in rheumatoid arthritis.

PMID- 15436607
TI  - Growth hormone and experimental diabetes.

PMID- 15436608
TI  - ACTH diabetes in man; the end-organ response versus the adrenocortical response.

PMID- 15436609
TI  - Studies on carbohydrate metabolism in adrenal cortical hypersecretion.

PMID- 15436610
TI  - Modification of the metabolic effects of adrenocorticotropic hormone and growth
      hormone by the administration of a diet high in potassium chloride.

PMID- 15436611
TI  - Observations on the pathogenesis of Cushing's syndrome.

PMID- 15436612
TI  - Pathways of corticosteroid synthesis.

PMID- 15436613
TI  - The islets of Langerhans in man visualized by phase contrast microscopy.

PMID- 15436614
TI  - The incidence of vascular disease in diabetes.

PMID- 15436615
TI  - The effect of desoxycorticosterone acetate (DCA) on blood pressure and renal
      function in human subjects.

PMID- 15436616
TI  - Studies on circulating growth hormone.

PMID- 15436617
TI  - Estrogenic interruption of broodiness in the fowl.

PMID- 15436618
TI  - Response to estrone of intraocular endometrial implants of littermates in female
      rabbits with uteri intact.

PMID- 15436619
TI  - Quantitative studies on the production of pseudopregnancy by estrogens.

PMID- 15436620
TI  - The agreement of clinical diagnosis with vaginal smears, as shown by the
      evaluation of symptoms, and glycogen index.

PMID- 15436621
TI  - The effect of steroid hormones applied directly to senile human skin.

PMID- 15436622
TI  - Oral administration of wheat germ oil concentrate as an aid in the reduction of
      pregnancy complications.

PMID- 15436623
TI  - The role of the liver and kidney in the metabolism of intravenous testosterone by
      human subjects.

PMID- 15436624
TI  - Frequency of retarded bone age in a group of enuretic children.

PMID- 15436625
TI  - Clinical experience with the use of cortisone acetate pellets in the treatment of
      adrenal cortical insufficiency.

PMID- 15436626
TI  - A study of adrenal cortical response in health and disease; the 48-hour ACTH
      test.

PMID- 15436627
TI  - The effects of ACTH, and of steroid compounds upon ketolysis in diabetic and
      nondiabetic human subjects.

PMID- 15436628
TI  - Administration and subsequent withdrawal of ACTH, studied simultaneously in a
      gouty father and his hyperuremic son.

PMID- 15436629
TI  - Increased adrenal cortical function accompanying prolonged remission induced by
      ACTH in myasthenia gravis.

PMID- 15436630
TI  - Adactar and adactar-gelatin: pituitary adrenocorticotropin preparations with
      prolonged activity.

PMID- 15436631
TI  - The effect of crude anterior preparation on haemopoiesis in normal,
      thyroidectomized and gonadectomized rats.

PMID- 15436632
TI  - Thyroid extract versus thyroxine; critical evaluation with particular reference
      to functional infertility.

PMID- 15436633
TI  - Thyrotoxin neuropathy.

PMID- 15436634
TI  - The treatment with desiccated thyroid of periodic behaviour disturbances
      associated with menses, in mentally defective patients.

PMID- 15436635
TI  - Hypopituitary myxedema, a non-cachectic form of Simmonds' disease; report of five
      cases, emphasizing the significance of plasma cholesterol levels.

PMID- 15436636
TI  - Cushing's syndrome from adrenal cortical tumor with special reference to the
      surgical mortality: a report of three cases and review of the literature.

PMID- 15436637
TI  - Growth and maturation in a case of idiopathic precocious puberty.

PMID- 15436638
TI  - Familial insulin-resistant diabetes mellitus.

PMID- 15436639
TI  - Adjuvant use of pregnenolone in seminal inadequacy.

PMID- 15436640
TI  - A simple method for the determination of neutral 17-ketosteroids, based on a
      novel means for the removal of interfering pigments.

PMID- 15436641
TI  - Studies with pregnenolone. 1. Nitrogen and electrolyte balance.

PMID- 15436642
TI  - Studies with pregnenolone. 2. Clinical applications.

PMID- 15436643
TI  - The effect of female hormones on the basal body temperature.

PMID- 15436644
TI  - The treatment of juvenile acne with topical estrogens.

PMID- 15436645
TI  - Acetoxypregnenolone.

PMID- 15436646
TI  - Adrenal cortical function in newly-born infants.

PMID- 15436647
TI  - Metabolic consequences of spinal cord injury.

PMID- 15436648
TI  - Alterations in testicular structure and function in organic disease of the
      pituitary.

PMID- 15436649
TI  - Physiologic effectiveness of oral progesterone.

PMID- 15436650
TI  - A case of pheochromocytoma: diagnosis by the benzodioxane test, urinary hormone
      studies, and nor-epinephrine assay of the tumor.

PMID- 15436651
TI  - The direct measurement of I131 uptake in the thyroid gland; further observations.

PMID- 15436652
TI  - Pregnancy test with the male frog (Rana ridibunda).

PMID- 15436653
TI  - Studies on adrenal function in sprue: preliminary report.

PMID- 15436654
TI  - The role of the fetal endocrine glands in development.

PMID- 15436655
TI  - Studies on the influence of the low sodium cardiac diet and the Kempner regimen
      on renal hemodynamics and electrolyte excretion in hypertensive subjects.

PMID- 15436656
TI  - Simultaneous determinations of the resting arteriovenous oxygen difference by the
      acetylene and direct Fick methods.

PMID- 15436657
TI  - The significance of the "one-minute" (prompt direct reacting) bilirubin in serum.

PMID- 15436658
TI  - Ventilatory function tests; voluntary ventilation capacity.

PMID- 15436659
TI  - Ventilatory function tests; factors affecting the voluntary ventilation capacity.

PMID- 15436660
TI  - Ventilatory function tests; resting ventilation, metabolism, and derived
      measures.

PMID- 15436661
TI  - Studies with inagglutinable erythrocyte counts; a method for measurement of net
      gain or deficit of red cells in the human subject.

PMID- 15436662
TI  - Studies with inagglutinable erythrocyte counts; analysis of mechanism of Cooley's
      anemia.

PMID- 15436663
TI  - Impaired vibratory sense in diabetes mellitus with proteinuria.

PMID- 15436664
TI  - The effect of varying quantities of inorganic iodide (carrier) on the urinary
      excretion and thyroidal accumulation of radioiodine in exophthalmic goiter.

PMID- 15436665
TI  - Cortisone in hypertensive vascular disease.

PMID- 15436666
TI  - Studies of the pulmonary and systemic arterial pressure in cases of patent ductus
      arteriosus with special reference to effects of surgical closure.

PMID- 15436667
TI  - Studies of diabetes mellitus: the relation of stressful life situations to the
      concentration of ketone bodies in the blood of diabetic and non-diabetic humans.

PMID- 15436668
TI  - The effects of concentrated salt-poor albumin on the metabolism and excretion of
      water and electrolytes in nephrosis and toxemia of pregnancy.

PMID- 15436669
TI  - Serum lipids in infectious hepatitis and obstructive jaundice.

PMID- 15436670
TI  - Comparison of the anterior pituitary-adrenal cortical stimulating effect of
      U.S.P. epinephrine, synthetic L-epinephrine, and nor-epinephrine.

PMID- 15436671
TI  - The man and quality in clinical investigation.

PMID- 15436672
TI  - Observations on brain embolism with special reference to the mechanism of
      hemorrhagic infarction.

PMID- 15436673
TI  - Effect of cortisone, adrenocorticotropic hormone (ACTH), and desoxycorticosterone
      acetate (DOCA) on serum lipids.

PMID- 15436674
TI  - Coagulation defect in hepatic disorders: deficiency of prothrombin-conversion
      accessory substances.

PMID- 15436675
TI  - Concentration of sodium in thermal sweat in patients with mental disease.

PMID- 15436676
TI  - A study of pyruvic acid in the blood, spinal fluid and urine of patients with
      liver disease and without hepatic coma.

PMID- 15436677
TI  - Molecular weight distributions of the globulins in the nephrotic syndrome.

PMID- 15436678
TI  - Clinical evaluation of crude and highly purified preparations of corticotropin
      (ACTH) obtained in good yield by simple laboratory procedure.

PMID- 15436679
TI  - Congenital adrenal hyperplasia associated with the adrenogenital syndrome: an
      attempt to correct its disordered hormonal pattern.

PMID- 15436680
TI  - Studies on portal circulation and alimentary absorption using superficial portal
      anastomotic veins.

PMID- 15436681
TI  - The effect of ACTH and cortisone on the metabolism of ascorbic acid.

PMID- 15436682
TI  - The effect of intravenous digoxin on the dynamics of the circulation in
      congestive heart failure.

PMID- 15436683
TI  - Effects of ACTH in patients with liver disease.

PMID- 15436684
TI  - The relationship of sodium depletion to carbohydrate metabolism.

PMID- 15436685
TI  - The evolution and significance of the hepatic granuloma in experimental
      brucellosis.

PMID- 15436686
TI  - Osmotic diuresis in diabetes insipidus.

PMID- 15436687
TI  - The use of abdominal supports in patients with angina pectoris as selected by the
      ballistocardiogram.

PMID- 15436688
TI  - Relationships of mixed alveolar-arterial oxygen and carbon dioxide gradients to
      exercise performance in patients with diseases of the heart or lungs.

PMID- 15436689
TI  - The problem of human radiocarbon fixation.

PMID- 15436690
TI  - The effect of previous immunization and x-irradiation upon the disposition in
      vivo of protein antigens labeled with radioactive iodine.

PMID- 15436691
TI  - The urinary excretion and biologic decay period of radiomercury labeling a
      mercurial diuretic in normal and diseased man.

PMID- 15436692
TI  - Studies on the mechanism of resistance to the 4-amino antagonists of
      pteroylglutamic acid in leukemia.

PMID- 15436693
TI  - The measurement of total body potassium by the radioisotope dilution technique.

PMID- 15436694
TI  - Urinary corticoids in acute leukemia (receiving ACTH and compound E) and in
      Cushing's syndrome.

PMID- 15436695
TI  - The use of the 24-hour endogenous creatinine clearance as a clinical measure of
      the functional state of the kidneys.

PMID- 15436696
TI  - A prolonged outbreak of infectious hepatitis in nurses due to a group of small
      children serving as a reservoir of the virus.

PMID- 15436697
TI  - The role of the reticulo-endothelial system and the adrenal cortex in the
      regulation of the plasma iron level.

PMID- 15436698
TI  - Measurement of blood flow and effects of cardiodynamics with a venous shunt in
      mitral stenosis.

PMID- 15436699
TI  - Multiple-balloon-kymographic recordings of the comparative action of banthine
      (ethyl dimethyl beta-9-xanthine carboxylate ethyl ammonium chloride) placebos,
      and tincture of belladonna on the motility of the upper small intestine in man.

PMID- 15436700
TI  - The effect of nitrogen mustard on renal manifestations of human
      glomerulonephritis.

PMID- 15436701
TI  - Study of gastric secretion of pepsin and pepsin inhibitors in peptic ulceration.

PMID- 15436702
TI  - Oxygen uptake and blood flow in the human kidney.

PMID- 15436703
TI  - The relation of "N," "S" and "salt" hormone effects to the manifestations of
      rheumatoid arthritis.

PMID- 15436704
TI  - Veratrum viride in the treatment of hypertensive vascular disease.

PMID- 15436705
TI  - Non-uniformity of alveolar gas in patients with pulmonary disease.

PMID- 15436706
TI  - B12 activity of the urine of normal subjects and of patients with pernicious
      anemia following oral and parenteral administration of the vitamin.

PMID- 15436707
TI  - The relation of cell metabolism to radiation susceptibility.

PMID- 15436708
TI  - A grass polysaccharide as an index of decreased glomerular permeability in renal
      diseases.

PMID- 15436709
TI  - The relation of the clotting mechanism and the hemolytic system in paroxysmal
      nocturnal hemoglobinuria.

PMID- 15436710
TI  - Observations on the administration of ammonium cation exchange resin to patients
      with cardiac edema.

PMID- 15436711
TI  - Carboxylic cation exchange resin studies in animals and humans.

PMID- 15436712
TI  - Competitive inhibition of metabolites: a mechanism for integration of
      biosynthesis.

PMID- 15436713
TI  - Studies on the life cycles of spirochetes.

PMID- 15436714
TI  - Increased sodium-retaining corticoid excretion in edema, with some observations
      on the effects of cortisone in nephrosis.

PMID- 15436715
TI  - The urinary excretion of hormones in men with liver disease.

PMID- 15436716
TI  - Circulatory dynamics in atrial septal defect.

PMID- 15436717
TI  - Physiological studies in pre and postoperative mitral stenosis.

PMID- 15436718
TI  - The treatment of chronic idiopathic ulcerative colitis with adrenocorticotrophic
      hormone.

PMID- 15436719
TI  - Renal function and edema in acute glomerulonephritis.

PMID- 15436720
TI  - The effect of chemotherapy on the tissue response to tuberculous infection as
      observed in vivo.

PMID- 15436721
TI  - Electrokymographic studies of postural alterations in the cardiac cycle and in
      the ventricular diameter.

PMID- 15436722
TI  - The comparative metabolic effects of ACTH, cortisone acetate, and "compound F"
      acetate in a patient with chronic lymphatic leukemia.

PMID- 15436723
TI  - Intracellular cation exchanges in metabolic alkalosis.

PMID- 15436724
TI  - Studies on pregnancy complicated by thyrotoxicosis or by myxedema.

PMID- 15436725
TI  - An epidemic of Q fever among employees of a rendering plant in Syracuse, New
      York.

PMID- 15436726
TI  - Lack of avitaminosis among chronic alcoholics. Its relation to fortification of
      cereal products and the general nutriture of the population.

PMID- 15436727
TI  - Studies on the functional state of the adrenal cortex during and following ACTH
      and cortisone therapy.

PMID- 15436728
TI  - The phenomenon of "congestion collapse"; its pathogenesis and significance.

PMID- 15436729
TI  - A quantitative study of renal excretion of digitoxin in the normal and cardiac
      subject.

PMID- 15436730
TI  - Changes in antipyrine, T1824 spaces and total body chloride following the rice
      diet.

PMID- 15436731
TI  - The relation of the adrenal to thyroid function.

PMID- 15436732
TI  - Hepatic cirrhosis. Factors contributing to the failure to excrete urinary sodium
      during the accumulation of ascites and edema.

PMID- 15436733
TI  - The demonstration of hemolysins in acquired hemolytic anemia.

PMID- 15436734
TI  - A study of spatial vectorcardiography: a comparison of three lead systems for
      representing the electrical forces of the heart in three dimensions.

PMID- 15436735
TI  - The effects of repeated streptococcal and pneumococcal pulmonary infections in
      the cardiovascular system of the rat.

PMID- 15436736
TI  - Blood lipoproteins and atherosclerosis.

PMID- 15436737
TI  - Pheochromocytoma and essential hypertension.

PMID- 15436738
TI  - The effect of fasting and cardiac failure upon heart muscle metabolism in man.

PMID- 15436739
TI  - Physiologic method for calculation of cross-sectional area of the mitral valve.

PMID- 15436740
TI  - An experimental study of alternating constipation and diarrhea.

PMID- 15436741
TI  - The cause of enhanced cervical venous pulsations during inspiration in subjects
      with congestive heart failure.

PMID- 15436742
TI  - Circulatory changes in pulmonary arterio-venous fistulas.

PMID- 15436743
TI  - The tagging of red blood cells and plasma proteins with radioactive chromium.

PMID- 15436744
TI  - Vasomotor tone in the lesser circulation, and its inhibition by
      tetraethylammonium chloride.

PMID- 15436745
TI  - Observations using adrenolytic drugs and surgery for tumors of the adrenal gland.

PMID- 15436746
TI  - Effect of tilt on cerebral oxygen metabolism in patients with arterial
      hypertension.

PMID- 15436747
TI  - Radioactive iodine uptake of the thyroid and plasma protein bound iodine in
      subacute thyroiditis.

PMID- 15436748
TI  - The destruction of thyroid tissue in the rat by the halogen, astatine.

PMID- 15436749
TI  - Increased resistance to osmotic lysis as an acquired change in the erythrocytes
      of patients with hepatogenous jaundice or biliary obstruction.

PMID- 15436750
TI  - Observations on the origin of the electrocardiogram: potential variations of
      single heart muscle fibers in situ.

PMID- 15436751
TI  - Modifying effect of steroid hormone therapy of human neoplastic disease as judged
      by radioactive phosphorous (P32) studies.

PMID- 15436752
TI  - The regulation of breathing during severe exercise.

PMID- 15436753
TI  - Life stress and water balance in diabetes mellitus.

PMID- 15436754
TI  - Coproporphyrin excretion in experimental liver injury.

PMID- 15436755
TI  - Two-stage measurement of the anticephalin activity of normal and abnormal
      plasmas.

PMID- 15436756
TI  - The use of intra-articular temperature measurement in the evaluation of anti
      arthritic agents.

PMID- 15436757
TI  - Plasma volume changes produced by inhalation of CO2.

PMID- 15436758
TI  - Methylandrostenediol, a non-virilizing steroid hormone with testosterone-like
      effects.

PMID- 15436759
TI  - Direct action of vitamin B12 upon human bone marrow; the effect of instillations
      of vitamin B12 and folic acid into the bone marrow as studied by histochemical
      techniques.

PMID- 15436760
TI  - Experimental studies of intramyocardial oxygen tension: increases consequent on
      breathing pure oxygen in normal hearts and at the borders of ischaemic areas.

PMID- 15436761
TI  - The serum iron in diseases of the liver.

PMID- 15436762
TI  - Changes in normal renal function resulting from ACTH and cortisone.

PMID- 15436763
TI  - The distribution of blood in the rabbit kidney.

PMID- 15436764
TI  - Metabolic studies during treatment of severe congestive heart failure with 50
      mgm. sodium diet.

PMID- 15436765
TI  - Studies on hematopoietic recovery from radiation injury.

PMID- 15436766
TI  - Evidence of simulated adrenal cortical activity during pregnancy in an addisonian
      patient.

PMID- 15436767
TI  - The hypertensive pattern in the critically damped ballistocardiogram.

PMID- 15436768
TI  - The unique function of certain components of complement in the hemolytic reaction
      of paroxysmal cold hemoglobinuria.

PMID- 15436769
TI  - The hemodynamic and renal functional effects of venous congestion of the limbs in
      patients with diabetes insipidus.

PMID- 15436770
TI  - Experiences with the use of cation exchange resins in the treatment of edema.

PMID- 15436771
TI  - Observations on a new oral diuretic compound (1-ethyl-3n propyl-4 amino-uracil).

PMID- 15436772
TI  - The response of the human colon to acetylcholine.

PMID- 15436773
TI  - Studies on amino acid excretion in man; effect of various protein supplements in
      a normal man, two patients with benign gastric ulcer and two patients with
      chronic ulcerative colitis.

PMID- 15436774
TI  - The significance of the plasma tocopherol concentration in liver disease, in the
      fasting state and following single test-doses of tocopherol.

PMID- 15436775
TI  - The use of a cation exchange resin in patients with cardiac edema.

PMID- 15436776
TI  - The distribution and the pathologic effects of I131 in man.

PMID- 15436777
TI  - The significance of urinary dehydroisoandrosterone.

PMID- 15436778
TI  - Salutary action of ACTH in a case of periarteritis nodosa: the effective dose as
      measured by nitrogen and electrolyte balances.

PMID- 15436779
TI  - The effects of induced hyperglycemia on renal oxygen consumption and blood flow.

PMID- 15436780
TI  - Characterization of the anemia of chronic renal insufficiency.

PMID- 15436781
TI  - Entero-hepatic circulation of bromsulphalein.

PMID- 15436782
TI  - A study of porphyrin and hemoglobin metabolism with the aid of glycine containing
      N15, in a case of chronic (mixed) porphyria.

PMID- 15436783
TI  - The value of the agglutination test in differentiating chronic active brucellosis
      from postinfectious neurasthenia.

PMID- 15436784
TI  - The effects of positive pressure breathing on air flow resistance of the
      tracheobronchial tree.

PMID- 15436785
TI  - Abnormal ballistocardiographic patterns in disease, as recorded with the low
      frequency, critically-damped ballistocardiograph.

PMID- 15436786
TI  - Time relations between the metabolic changes of experimental diabetic acidosis
      and adrenal cortical hyperfunction.

PMID- 15436787
TI  - Association of high ionized serum calcium with renal failure in plasma cell
      myeloma.

PMID- 15436788
TI  - Chloramphenicol-fastness: in vivo and in vitro.

PMID- 15436789
TI  - The effects of protoveratrine, a pure veratrum alkaloid in hypertensive patients.

PMID- 15436790
TI  - The effect of a synthetic fat-free dietary regimen on serum cholesterol.

PMID- 15436791
TI  - The effect of spinal anesthesia and arterial and venous occlusion on the digital
      circulation.

PMID- 15436792
TI  - The production of a pressor response in patients with refractory hypotension by
      use of the artificial kidney.

PMID- 15436794
TI  - Electrolyte exchange between body fluid compartments during recovery from
      congestive heart failure.

PMID- 15436793
TI  - The nephrotic syndrome in children: response to intravenous sodium loads.

PMID- 15436795
TI  - The role of adrenal cortex in alanine metabolism.

PMID- 15436797
TI  - Enzymatic characteristics of the hemolytic principle of mumps virus.

PMID- 15436796
TI  - The effect of adrenocorticotropic hormone and cortisone on antibody production in
      human beings.

PMID- 15436798
TI  - Studies on the mechanisms of saline diuresis.

PMID- 15436799
TI  - The hepatic blood flow in Laennec's cirrhosis, with an estimate of the relative
      contributions from portal vein and hepatic artery.

PMID- 15436800
TI  - A rational interpretation of the dilution curves obtained by the dye injection
      method of Stewart and Hamilton for cardiac output.

PMID- 15436801
TI  - Alterations in sodium excretion, glomerular filtration and cardiac output in
      normal subjects.

PMID- 15436802
TI  - The effect of concentrated salt-poor human albumin on the excretion of water and
      electrolytes in normal dogs.

PMID- 15436803
TI  - The role of the spleen in the regulation of the peripheral blood leukocyte level.

PMID- 15436804
TI  - Studies of renal and hepatic function in normal man during thiopental,
      cyclopropane and high spinal anesthesia.

PMID- 15436805
TI  - Metabolic effects of ACTH in acute leukemia.

PMID- 15436806
TI  - Cortisone in hypertensive vascular disease.

PMID- 15436807
TI  - Cardiac catheterization following acute myocardial infarction.

PMID- 15436808
TI  - The effect of sodium intake on the action of ACTH in uncomplicated essential
      hypertension.

PMID- 15436809
TI  - Antibody response after hemolytic streptococcal respiratory infection in
      childhood.

PMID- 15436810
TI  - Plasma proteolytic activity in pneumonia.

PMID- 15436811
TI  - Comprehensive analysis of ventilatory and circulatory factors in relation to gas
      exchange.

PMID- 15436812
TI  - The effect of poliomyelitis virus upon cells in tissue cultures.

PMID- 15436813
TI  - Influence of ACTH on the excretion of histamine and histidine in patients with
      allergic states or rheumatoid arthritis.

PMID- 15436814
TI  - The dependence of water diuresis upon electrolyte excretion.

PMID- 15436815
TI  - The blood volume in congestive heart failure.

PMID- 15436816
TI  - The practical application of a hemagglutination reaction in pulmonary
      tuberculosis.

PMID- 15436817
TI  - Relation of plasma cell growth to abnormal serum protein components and Bence
      Jones proteinuria in multiple myeloma.

PMID- 15436818
TI  - Antistreptolysin "O" in urine and serum of patients with the nephrotic syndrome.

PMID- 15436819
TI  - Management of respiratory center failure in bulbar poliomyelitis with
      electrophrenic respiration.

PMID- 15436820
TI  - Involvement of the left ventricle is of primary importance in constrictive
      pericarditis.

PMID- 15436821
TI  - Cerebral metabolism in pernicious anemia.

PMID- 15436822
TI  - Pherentasin: a pressor substance present in arterial hypertension.

PMID- 15436823
TI  - Observations on electrolyte balance during mercurial diuresis in congestive heart
      failure.

PMID- 15436824
TI  - Interactions between gluco-corticoid and mineralo-corticoid hormones.

PMID- 15436825
TI  - Studies on the mechanisms of some anemias with biologically tagged erythrocytes.

PMID- 15436826
TI  - The relation of bone marrow metastases to the anemia of cancer patients.

PMID- 15436827
TI  - The enzymatic degradation of nucleic acids in purulent exudates by
      streptodornase.

PMID- 15436828
TI  - Estimation of plasmin activity by radioactive measurement.

PMID- 15436829
TI  - Asymptomatic hyponatremia in pulmonary tuberculosis.

PMID- 15436830
TI  - Study of human serum based on analysis of fractions obtained in the quantity
      ultracentrifuge.

PMID- 15436831
TI  - The relation of the cerebral O2 consumption to the total body metabolism in
      hyperthyroidism.

PMID- 15436832
TI  - The relationship between serum quinidine concentrations and the prevention and
      treatment of cardiac arrhythmias.

PMID- 15436833
TI  - The inhibitory effect of saturating doses of para-aminohippurate on renal tubular
      reabsorption of sodium in man.

PMID- 15436834
TI  - A rapid bedside method for the determination of urinary sodium content.

PMID- 15436835
TI  - Effects of injections of hypertonic glucose on metabolism of electrolytes in
      edematous patients.

PMID- 15436836
TI  - The role of antibody in "allergic" encephalomyelitis.

PMID- 15436837
TI  - The relation of influenza epidemics in Ohio to primary pneumococcic pneumonia of
      the Cincinnati General Hospital, 1936-1949.

PMID- 15436838
TI  - Hypertension following bilateral nephrectomy.

PMID- 15436839
TI  - Effects of ACTH on tuberculosis in humans.

PMID- 15436840
TI  - HLZP--a new zinc protein in human leucocytes.

PMID- 15436841
TI  - The effect of ACTH on blood complement, gamma globulins, and fibrinogen.

PMID- 15436842
TI  - Induced variations in pulmonary arterial and pulmonary capillary pressures in
      man.

PMID- 15436843
TI  - Nitrogen exchange and caloric expenditure in patients with malignant neoplasms.

PMID- 15436844
TI  - Nitrogen and electrolyte balance in hypertensive patients on the rice diet.

PMID- 15436845
TI  - The effect of auricular fibrillation on cardiac output, coronary flow and
      arterial blood pressure.

PMID- 15436846
TI  - The sternal marrow in diffuse pulmonary disease.

PMID- 15436847
TI  - The effect of mercurial diuretics on urinary ammonia and titratable acidity
      excretion during acidosis in man.

PMID- 15436848
TI  - Observations on the emotional and symptomological effects of telling adults that
      they might have heart disease.

PMID- 15436849
TI  - Fecal fatty acids and other lipids: a study of two normal human adults taking (1)
      a diet free of lipid and (2) a diet containing triolein as the only lipid.

PMID- 15436850
TI  - Studies of alternating sinusoidal currents introduced into the heart in life and
      death.

PMID- 15436851
TI  - The influence of temperature upon venous pressure in the foot.

PMID- 15436852
TI  - Resistance to small doses of insulin in various clinical conditions.

PMID- 15436853
TI  - Studies on amino acid excretion in man. IV. Peptic ulcer.

PMID- 15436855
TI  - Studies on amino acid excretion in man. V. Chronic ulcerative colitis and
      regional enteritis.

PMID- 15436856
TI  - The prothrombin conversion accelerator of serum (SPCA): its partial purification
      and its properties compared with serum AC-globulin.

PMID- 15436857
TI  - Treatment of nephrosis with concentrated human serum albumin. II. Effects on
      renal function and on excretion of water and some electrolytes.

PMID- 15436858
TI  - Free erythrocyte protoporphyrin.

PMID- 15436859
TI  - The effect of "rice diet" on plasma volume and extracellular fluid space in
      hypertensive subjects.

PMID- 15436860
TI  - The effect of diethylstilbestrol on the calcium phosphorus and nitrogen
      metabolism of prostatic carcinoma.

PMID- 15436861
TI  - Studies on VEM and VDM in blood in relation to renal hemodynamics and renal
      oxygen extraction in chronic congestive heart failure.

PMID- 15436862
TI  - An example of cellular hyperosmolarity.

PMID- 15436863
TI  - The acute circulatory effects of the head-down position (negative G in normal
      man, with a note on some measures designed to relieve cranial congestion in this
      position.

PMID- 15436864
TI  - The effect of adrenocorticotropic hormone in panhypopituitarism.

PMID- 15436865
TI  - Salt retention in cirrhosis of the liver.

PMID- 15436866
TI  - The comparative absorption of vitamin A from a water-miscible and an oily
      preparation by normal human adults and patients with steatorrhea.

PMID- 15436867
TI  - The transfer of radioactive mercury across a membrane produced by the application
      of cantharides to the skin of man.

PMID- 15436868
TI  - Metabolic and cardiovascular studies of prolonged intravenous administration of
      human serum albumin.

PMID- 15436869
TI  - Cerebral circulation and metabolism in hyperthyroidism.

PMID- 15436870
TI  - Studies in para-aminohippuric acid synthesis in the human: its application as a
      liver function test.

PMID- 15436871
TI  - The mechanism of glycosuric diuresis in diabetic man.

PMID- 15436872
TI  - Concentration of precipitable iodine in the serum.

PMID- 15436873
TI  - Plasma and red cell iron turnover in normal subjects and in patients having
      various hematopoietic disorders.

PMID- 15436874
TI  - The effect of alcohol on the renal excretion of water and electrolyte.

PMID- 15436875
TI  - Studies on a proteolytic enzyme system of the blood. II. Fibrinolysokinase
      activators for profibrinolysin.

PMID- 15436876
TI  - A correlative study of the cardiac output and the hepatic circulation in
      hyperthyroidism.

PMID- 15436877
TI  - Iron metabolism; hematopoiesis following phlebotomy; iron as a limiting factor.

PMID- 15436878
TI  - Mucolytic enzyme systems. X. Serum hyaluronidase inhibitor in liver disease.

PMID- 15436879
TI  - The position of the oxygen dissociation curve of the blood in normal children and
      adults.

PMID- 15436880
TI  - The position of the oxygen dissociation curve of the blood in cyanotic congenital
      heart disease.

PMID- 15436881
TI  - The effect of salicylates and adrenocorticotropic hormone upon the miscible pool
      of uric acid in gout.

PMID- 15436882
TI  - Performance of catarrhine monkeys on a series of discrimination reversal
      problems.

PMID- 15436883
TI  - Incidental learning in the rat.

PMID- 15436884
TI  - Habit reversal after electroshock convulsions as a function of the difficulty of
      the tasks.

PMID- 15436885
TI  - Influence of handedness of acetylcholine locally applied with other chemicals to
      the cerebral cortex of the rat.

PMID- 15436886
TI  - The effects of intra-maze delay; tetanizing shock during various intervals of
      delay.

PMID- 15436887
TI  - A note on the genetic basis of spontaneous activity in the albino rat.

PMID- 15436888
TI  - Learning and satiation of response in intrinsically motivated complex puzzle
      performance by monkeys.

PMID- 15436889
TI  - Experimental analysis of the hoarding habit in the rat; preliminary observations.

PMID- 15436890
TI  - The dynamic characteristics of the semicircular canals.

PMID- 15436891
TI  - Gustatory nerve discharges in normal and adrenalectomized rats.

PMID- 15436892
TI  - The nature of the memory decrement following electroconvulsive shock.

PMID- 15436893
TI  - The concept of an ideal therapeutic relationship.

PMID- 15436894
TI  - Play therapy with well-adjusted retarded readers.

PMID- 15436895
TI  - The use of limits in reading therapy.

PMID- 15436896
TI  - A client-centered approach to vocational counseling.

PMID- 15436897
TI  - A factor analysis of Rorschach scoring categories.

PMID- 15436898
TI  - Psychological constriction on several projective tests.

PMID- 15436899
TI  - Objective Rorschach "signs" for groups of normal, maladjusted and
      neuropsychiatric subjects.

PMID- 15436901
TI  - Rorschach "populars" as a function of the length of record.

PMID- 15436900
TI  - Rorschach human and other movement responses in relation to intelligence.

PMID- 15436902
TI  - Discrimination of the types of schizophrenia by the Wechsler-Bellevue Scale.

PMID- 15436903
TI  - The Wechsler-Bellevue psychometric pattern in anxiety neurosis.

PMID- 15436904
TI  - Intellectual deterioration in the aged: agreement between the Wechsler-Bellevue
      and the Babcock-Levy.

PMID- 15436905
TI  - Intelligence test scores of newly blinded soldiers.

PMID- 15436906
TI  - Serial versus consecutive order administration of the Stanford-Binet Intelligence
      Scales.

PMID- 15436907
TI  - The teaching of psychotherapy through content-free interviews.

PMID- 15436908
TI  - The MMPI as diagnostic differentiator: a reply to Rubin.

PMID- 15436909
TI  - A note on "Reply to Rubin.".

PMID- 15436910
TI  - Correction of "The relationship between variability and ability on the Wechsler
      Bellevue.".

PMID- 15436911
TI  - The pathogenesis of desquamative gingivitis: a disturbance of the connective
      tissue ground substance.

PMID- 15436912
TI  - Studies in the regeneration and reattachment of supporting structures of the
      teeth; soft tissue reattachment.

PMID- 15436913
TI  - The oxygen consumption of healing gingiva.

PMID- 15436914
TI  - Bacterial growth and crystal formation: a possible factor in calculus formation.

PMID- 15436915
TI  - Physiological tooth migration and its significance for the development of
      occlusion; the biogenesis of overbite.

PMID- 15436916
TI  - Masticatory performance and efficiency.

PMID- 15436917
TI  - Electrical action currents during mastication; measurement of the effort exerted
      in chewing various foods.

PMID- 15436918
TI  - Hygroscopic expansion of some casting investments.

PMID- 15436919
TI  - Clinical observations on a contracting amalgam alloy.

PMID- 15436920
TI  - Low temperature polymerization of acrylic resins.

PMID- 15436921
TI  - Thermal conductivity of dentin.

PMID- 15436922
TI  - The citric acid content of human teeth.

PMID- 15436923
TI  - The location of the glycolytic enzymes in saliva.

PMID- 15436924
TI  - The effect of partly synthetic diets on the dental caries incidence in Syrian
      hamsters.

PMID- 15436925
TI  - Preliminary studies of the caries inhibiting potential and acute toxicity of
      sodium monofluorophosphate.

PMID- 15436927
TI  - Variability in dental caries experience and its implication upon sample size.

PMID- 15436926
TI  - The Evanston Dental Caries Study; a comparison of the prefluoride with the
      postfluoride caries experience of 6-, 7-, and 8-year old children in the study
      area (Evanston, III.).

PMID- 15436929
TI  - Electron microscopy of human dentin.

PMID- 15436928
TI  - Intravital uptake of fluorides by the teeth under various conditions.

PMID- 15436930
TI  - The role of non-precipitating antibodies in the passive sensitization of human
      skin by rabbit anti-ovalbumin.
AB  - Sera of fourteen rabbits injected with alum-precipitated recrystallized
      ovaltumin, containing 0.046 to 0.604 mg. of precipitable antibody nitrogen per
      ml. (average 0.299 mg.), passively sensitized human skin, while the sera of nine
      rabbits injected with dissolved recrystallized ovalbumin, containing from less
      than 0.05 to 0.420 of antibody nitrogen per ml. (average 0.176 mg. or less), were
      inactive in human skin. The skin-sensitizing activity of the sera bore no
      relation to the precipitin content. Removal of 68 to 90 per cent of the
      precipitin nitrogen by a single addition of antigen did not affect the activity
      of the sera in sensitizing human skin. Removal of all precipitable antibody
      nitrogen in one serum by a single addition of antigen removed the skin
      sensitizing activity. The "univalent" antibody remaining after complete removal
      of precipitin by fractional addition of antigen showed the same activity in
      passive sensitization of human skin as the original serum.

PMID- 15436931
TI  - The crystallization and serological differentiation of a streptococcal proteinase
      and its precursor.
AB  - Grown in dialysate broth at a pH between 5.5 and 6.5, some strains of group A
      streptococci elaborate the precursor of a proteolytic enzyme. Within this range
      of hydrogen concentration the precursor is also produced when the streptococci
      are suspended in a peptone dialysate containing glucose and incubated at 37
      degrees C. The precursor does not appear to be produced at a neutral or alkaline
      reaction. Methods are described whereby the precursor and proteinase have been
      isolated in crystalline form. The precursor crystallizes from half-saturated
      ammonium sulfate at pH 8.0 and a temperature of 22 degrees C. or higher; the
      proteinase crystallizes from 0.15 saturated ammonium sulfate at pH 8.0 but does
      so most readily at refrigerator temperature. The degree of purification achieved
      by these procedures is discussed. The activity of purified preparations of the
      precursor and of proteinase has been tested against alpha-benzoyl-l-arginineamide
      and, with this as a substrate, the conversion of precursor to proteinase by
      autocatalysis or by trypsin has been confirmed. Immunological experiments are
      described, the results of which provide evidence of the distinct antigenic
      specificity of the precursor and proteinase; the conversion of precursor to
      proteinase has been followed by means of serological tests.

PMID- 15436932
TI  - The purification and properties of streptolysin S.
AB  - Considerable purification of streptolysin S has been achieved by fractionation of
      crude bacterial filtrates with methanol, under controlled conditions of pH, ionic
      strength, and temperature. The final material (P III) consisted of two
      electrophoretic components. The purified material was employed for kinetic
      studies, the results of which were confirmed with hemolysin isolated
      electrophoretically from P III. The heat of activation (temperature
      characteristic) of streptolysin S was found to be 17,900 calories per mole. Time
      dilution curves of the hemolysin were found to be sigmoid. The influence of
      certain ions and lipids on the course of hemolysis was investigated. The
      significance of the prolonged lag period and of the deviation in the behavior of
      streptolysin S from Ponder's equation has been discussed.

PMID- 15436933
TI  - Studies on the life cycle of spirochetes; the life cycle of the Nichols
      pathogenic Treponema pallidum in the rabbit testis as seen by phase contrast
      microscopy.
AB  - A series of observations with the phase contrast microscope on the occurrence of
      a complex life cycle in the pathogenic Treponema pallidum as it occurs in the
      syphilitic rabbit testis has been presented and it seems likely from these
      observations that there are two means of vegetative reproduction, consisting of
      (1) transverse division (the most important under usual conditions); and (2) the
      production of gemmae or buds which eventuate into unispirochetal cysts comparable
      to those described for saprophytic forms, within each of which single spirochetes
      develop and differentiate, and from which they subsequently emerge. In addition
      preliminary evidence is presented which suggests that a more complex process is
      involved in which multispirochetal cysts develop following aggregation of two or
      more organisms. Within each of these larger cysts numerous organisms develop and
      subsequently emerge as tangled ropes. Following emergence, they subsequently
      undergo transverse division and gemmae formation, and so reproduce vegetatively.
      Subsequent papers will elaborate upon these processes.

PMID- 15436934
TI  - Studies on the life cycle of spirochetes; the life cycle of the Nichols
      pathogenic Treponema pallidum in the rabbit testis as visualized by means of
      stained smears.
AB  - Further evidence for the occurrence of a complex life cycle in the pathogenic
      Treponema pallidum as visualized by means of stained preparations is presented.

PMID- 15436935
TI  - Studies on acute disseminated encephalomyelitis produced experimentally in Rhesus
      monkeys; complement-fixing antibodies.
AB  - 1. Animals injected with emulsions of monkey brain with adjuvants show a complex
      pattern of antibody response as determined by complement fixation tests. 2. Organ
      specific complement-fixing antibodies to constituents of brain tissue may be
      formed which fix complement with brain tissues of various animal species but fail
      to react with other organs or with rabbit placenta. 3. Antibodies may be formed
      to some constituent of brain other than nervous tissue. It would seem that these
      can be detected by the strong complement fixation given with rabbit placenta. 4.
      Sera from individual animals may contain antibodies to the brain or placenta
      constituents, to both, or to neither. Occasional individual sera show unique
      patterns of antibody response as determined with various additional antigens such
      as fetal brain, posterior pituitary, or peripheral nerves. 5. No evidence of any
      etiological relationship between the development of encephalomyelitis and the
      complement-fixing antibodies to brain demonstrable in the sera could be found.
      The complement-fixing antibody to the placental constituent was unrelated to the
      encephalomyelitis.

PMID- 15436936
TI  - Studies on the agent of infectious hepatitis; propagation of the agent in tissue
      culture and in the embryonated hen's egg.
AB  - Two viral agents have been procured from patients with infectious hepatitisin two
      widely separated outbreaks of the disease by transfer of acute stage serum and
      stool filtrates to and passage in tissue cultures of rabbit liver cells in roller
      tubes and minced chick embryos in Simms-Sanders medium followed by passage in the
      amniotic cavity of the chick. Cultures of both agents, designated the Akiba and
      NL strains of virus, induced mild hepatitis without jaundice in the majority of
      volunteers tested after an incubation period of from 9 to 38 days. Although these
      agents have not been identified definitely as the virus of infectious hepatitis,
      the available evidence, as discussed, is compatible with the suggestion that such
      they are.

PMID- 15436938
TI  - An experimental analogue of repression; the effect of individual failure and
      success on memory measured by relearning.

PMID- 15436937
TI  - Studies on the agent of infectious hepatitis; the disease produced in human
      volunteers by the agent cultivated in tissue culture or embryonated hen's eggs.
AB  - The successful cultivation of the virus of infectious hepatitis in chick embryo
      tissue culture and in the amniotic cavity of the embryonated hen's egg is
      supported by a comparison of the disease induced in volunteers by the cultivated
      virus with hepatitis without jaundice resulting from experimental infection with
      natural infectious hepatitis virus. Both types of viral preparations produced
      illnesses in comparable percentages of volunteers (83 and 75 per cent,
      respectively) after similar average periods of incubation (24.4 and 23.4 days,
      respectively) and of similar average duration (28.3 and 27.6 days, respectively).
      The disease could be divided in both groups of patients into a primary stage,
      followed after a short interval of relative well being by the secondary stage.
      The illnesses in both instances were characterized by anorexia, nausea, vomiting,
      enlarged, tender livers and abnormal liver function tests, and frequently
      temperature elevations. They differed in that jaundice was observed in 31 per
      cent of the cases resulting from infection with natural virus but not in any
      patients infected with the cultivated virus.

PMID- 15436939
TI  - The effect of different types of preliminary activities on subsequent learning of
      paired-associate material.

PMID- 15436940
TI  - Stimulus pre-differentiation as a factor in transfer of training.

PMID- 15436941
TI  - Retention as a function of stage of practice.

PMID- 15436942
TI  - A quantitative comparison of the discriminative and reinforcing functions of a
      stimulus.

PMID- 15436943
TI  - Resistance to extinction of a conditioned operant as related to drive level at
      reinforcement.

PMID- 15436944
TI  - The effect of extinction upon rate of reconditioning.

PMID- 15436945
TI  - A study of concept formation as a function of reinforcement and stimulus
      generalization.

PMID- 15436946
TI  - The learning and retention of concepts; the influence of form of presentation.

PMID- 15436947
TI  - Sensory conditioning measured by the facilitation of auditory acuity.

PMID- 15436948
TI  - The relation of vernier and depth discrimination to width of test rod.

PMID- 15436949
TI  - An experiment on the expressiveness of shell and textile 'montages'.

PMID- 15436950
TI  - An hypothesis concerning the generation and use of synonyms.

PMID- 15436951
TI  - The relationship between the tilt of a visual field and the deviation of body
      position from the vertical in the white rat.

PMID- 15436952
TI  - [Histological diagnosis of bronchic cancer by examination of secretions taken
      during bronchoscopy].

PMID- 15436953
TI  - [Surgical treatment of pulmonary suppurations].

PMID- 15436954
TI  - [Exertion dyspnea and its physio-pathologic mechanism].

PMID- 15436955
TI  - [Pulmonary and bronchic nomenclature].

PMID- 15436956
TI  - [Neurologic form of cancer of the pulmonary apex with hydro-pneumothorax].

PMID- 15436957
TI  - [Kahler's disease localized in the thorax, with bilateral involvement of the
      pleura, diagnosed by systematic radiography].

PMID- 15436958
TI  - [Sternberg's leukosarcomatosis].

PMID- 15436959
TI  - [Lymphoid leukemia and cancer of the lung].

PMID- 15436960
TI  - [Pseudo intra-thoracic tumors due to encysted pleurisy].

PMID- 15436961
TI  - [On surgical exeresis and the notion of evolution of bronchial dilatations].

PMID- 15436962
TI  - Cytologic diagnosis of malignant disease.

PMID- 15436963
TI  - Chronic pyuria in infants and children.

PMID- 15436964
TI  - The prediabetic state and its clinical importance.

PMID- 15436965
TI  - Acute renal insufficiency; a review.

PMID- 15436966
TI  - Cotton from Bikini; chromosome irregularities found in plants grown from seed
      exposed to gamma radiation.

PMID- 15436967
TI  - A new mutation with asymmetrical expression in the mouse.

PMID- 15436968
TI  - Effects of atomic bomb radiations and x-rays on seeds of cereals; a comparison of
      the effects of ionizing radiations from the "test Able" atomic bomb and from x
      rays on seeds of barley, wheat and oats.

PMID- 15436969
TI  - The Pelger-anomaly in man and rabbit; a mendelian character of the nuclei of the
      leucocytes.

PMID- 15436970
TI  - Inheritance of brown and green mature fruit color in peppers.

PMID- 15436971
TI  - William Henry Welch.

PMID- 15436972
TI  - Thomas Harris, M. D., naval surgeon and founder of the first school of naval
      medicine in the New World.

PMID- 15436973
TI  - Augustus Bozzi Granville; a medical knight-errant.

PMID- 15436974
TI  - A link with Jenner--postscript.

PMID- 15436975
TI  - James Currie and hydrotherapy.

PMID- 15436976
TI  - Michael Underwood: a surgeon practicing midwifery from 1764 to 1784.

PMID- 15436977
TI  - Observations on fused kidneys with horseshoe configuration: the contribution of
      Leonardo Botallo (1564).

PMID- 15436978
TI  - Science resurrected.

PMID- 15436979
TI  - The effect of adrenocorticotrophic hormone on circulating antibody levels.

PMID- 15436980
TI  - A nomographic probit solution for the median effective dose (ED50).

PMID- 15436981
TI  - A quantitative complement fixation test: titration of luetic sera by the unit of
      50 per cent hemolysis.

PMID- 15436982
TI  - The action of enzymes in hemagglutinating systems. II. Agglutinating properties
      of trypsin-modified red cells with anti-Rh sera.

PMID- 15436983
TI  - Antigen-antibody reactions in agar. I. Complexity of antigen-antibody systems as
      demonstrated by a serum-agar technic.

PMID- 15436984
TI  - Tuberculostatic activity of blood and urine from animals given gliotoxin.

PMID- 15436985
TI  - A general method for the specific purification of antiprotein antibodies.

PMID- 15436986
TI  - The hypotensive action of influenza virus on rats.

PMID- 15436987
TI  - Anti (streptococcal) desoxyribonuclease. Occurrence in the sera of patients
      treated with streptococcal concentrates containing streptodornase.

PMID- 15436988
TI  - Quantitative studies of the relationship between fecal and serum antibody.

PMID- 15436989
TI  - Serological relationships existing between bacterial parasites and their hosts.
      I. Antibodies in human blood serum for native intestinal bacteria.

PMID- 15436990
TI  - Serological relationships existing between bacterial parasites and their hosts.
      II. The agglutination of intestinal bacteria by blood serum from human beings and
      animals not known to carry the strains tested.

PMID- 15436991
TI  - Cytochemical studies on the intranuclear inclusion of herpes simplex.

PMID- 15436992
TI  - The effect of terramycin on the PR8 strain of influenza A virus in chick embryos
      and mice.

PMID- 15436993
TI  - Studies of the protective effect of gamma globulin against herpes simplex
      infections in mice.

PMID- 15436994
TI  - Combined active-passive re-immunization against tetanus in previously immunized
      individuals: experimental and clinical evidence.

PMID- 15436995
TI  - The antigenic relationships of certain viruses capable of producing encephalitis
      in mice, as shown by complement fixation tests.

PMID- 15436996
TI  - The antigenic relationships of native antigens of species of Brucella.

PMID- 15436997
TI  - A new method for the large-scale production of high-titre botulinum formol-toxoid
      types C and D.

PMID- 15436998
TI  - The action of aureomycin and other chemotherapeutic agents in experimental
      brucellosis.

PMID- 15436999
TI  - The interchangeability of the complement components of different animal species
      in the hemolysis of sheep erythrocytes sensitized with rabbit amboceptor.

PMID- 15437000
TI  - Q fever in California; recovery of Coxiella burnetii from naturally-infected air
      borne dust.

PMID- 15437001
TI  - Differences in toxicity of the S- and R-variants of Shigella dysenteriae.

PMID- 15437002
TI  - A comparison of influenza complement fixation antigens derived from allantoic
      fluids and membranes.

PMID- 15437003
TI  - Evaluation of the agglutination of erythrocytes sensitized by Newcastle disease
      virus (NDV) as a serologic test in infectious mononucleosis.

PMID- 15437004
TI  - A comparison of physicochemical measurements of hyaluronidase and of neutralizing
      antibodies thereto.

PMID- 15437005
TI  - The egg-white inhibitor of influenza virus hemagglutination; stability in
      relation to the preparation of a standard of activity.

PMID- 15437006
TI  - Hemagglutinating substances for human cells in various Egyptian plants.

PMID- 15437007
TI  - The electron microscopy of fowl pox virus within the chorioallantoic membrane.

PMID- 15437008
TI  - Acetyl-choline-stimulator and inhibitor.

PMID- 15437009
TI  - Indications for pulmonary resection.

PMID- 15437010
TI  - Tetanus--its management.

PMID- 15437011
TI  - Labour in occipitoposterior position and its management.

PMID- 15437012
TI  - Senile enlargement of prostate; pathological aspect.

PMID- 15437014
TI  - A severe case of infectious hepatitis with coma.

PMID- 15437013
TI  - Occupational hazards in coal gas manufacture and distribution.

PMID- 15437015
TI  - An unusual complication after cataract operation.

PMID- 15437016
TI  - A misleading case of severe constipation.

PMID- 15437017
TI  - AUTONOMIC nervous system & mediation of nerve impulses.

PMID- 15437018
TI  - The diagnosis of intracranial tumor.

PMID- 15437019
TI  - The treatment of arthritis.

PMID- 15437021
TI  - An unusual physical finding in a case of left ventricular aneurysm.

PMID- 15437020
TI  - Perforative appendicitis complicating the pregnancy of a woman with situs
      transversus viscerum; case report.

PMID- 15437022
TI  - The Four Doctors, forty-five years after.

PMID- 15437023
TI  - The effects of viruses on intraocular tissues; infections with the viruses of
      herpes simplex, feline agranulocytosis and ornithosis.

PMID- 15437024
TI  - The sensitivity of Gaffkya tetragena strains to penicillin and streptomycin.

PMID- 15437025
TI  - The sensitivity of Gaffkya tetragena strains to penicillin and streptomycin.

PMID- 15437026
TI  - The complement fixation inhibition test and its application to the diagnosis of
      ornithosis in chickens and in ducks; principles and technique of the test.

PMID- 15437027
TI  - The complement fixation inhibition test and its application to the diagnosis of
      ornithosis in chickens and in ducks; confirmation of the specificity and
      epidemiological application of the test.

PMID- 15437028
TI  - The dynamics of hemolysin formation in intact and splenectomized rabbits.

PMID- 15437029
TI  - In vitro sensitivity of pathogenic enteric bacteria to various antibiotics.

PMID- 15437030
TI  - Comparison of the erythrocyte and leukocyte cell surfaces of guinea pigs by use
      of agglutination techniques.

PMID- 15437031
TI  - The parasitemia in experimental toxoplasmosis.

PMID- 15437032
TI  - Effect of high concentrations of nicotinic acid and nicotinamide on growth of
      some streptococci and pneumococci.

PMID- 15437033
TI  - Chemotherapy of Trichomonas foetus in the chicken embryo; cultivation techniques.

PMID- 15437035
TI  - Morbidity after prostatectomy: a urethrocystographic study.

PMID- 15437034
TI  - Chemotherapy of Trichomonas foetus in the chicken embryo; drug screening
      experiments.

PMID- 15437036
TI  - Clinical and roentgenologic manifestations of obstruction of the small bowel.

PMID- 15437037
TI  - Kuntscher nail technic for fractures of femoral shaft.

PMID- 15437038
TI  - Management of urinary incontinence in women.

PMID- 15437039
TI  - Prevention of some post-gastrectomy difficulties by new gastrectomy technic;
      (pantaloon anastomosis).

PMID- 15437040
TI  - Primary carcinoma of the duodenum report of a successful Whipple operation.

PMID- 15437041
TI  - Unicornuate uterus associated with agenesis of the kidney; report of 2 cases.

PMID- 15437042
TI  - A study on the cause of toxemia of pregnancy.

PMID- 15437043
TI  - Management of acute cholecystitis.

PMID- 15437044
TI  - A sirenomelian monster.

PMID- 15437045
TI  - Torsion of an epiploic appendage simulating torsion of an ovarian cystoma.

PMID- 15437046
TI  - Meigs' syndrome; report of a case.

PMID- 15437047
TI  - A new technic in photography with the use of ultra violet rays.

PMID- 15437048
TI  - Thorium-x investigations: histological study of thorium-x application on rabbit
      skin.

PMID- 15437049
TI  - Cutaneous sarcoidosis as an expression of syphilis.

PMID- 15437050
TI  - The relationship of host and virus in molluscum contagiosum.

PMID- 15437051
TI  - The etiology of poral closure; an experimental study of miliaria rubra, bullous
      impetigo and related diseases of the skin. I. An historical review of the
      causation of miliaria.

PMID- 15437052
TI  - The etiology of poral closure. II. The role of staphylococcal infection in
      miliaria rubra and bullous impetigo.

PMID- 15437053
TI  - The etiology of poral closure. III. The pathologic effect of excessive soaping on
      the pores of the skin.

PMID- 15437054
TI  - The etiology of poral closure. IV. The effect of lipoid solvents on the pores of
      the skin; final discussion on poral closure.

PMID- 15437055
TI  - Comments to "The etiology of poral closure, an experimental study of miliaria
      rubra, bullous impetigo and related diseases of the skin. By John P. O'Brien, M.
      D.".

PMID- 15437056
TI  - The gallbladder and common duct problem as seen by the general practitioner and
      general surgeon.

PMID- 15437057
TI  - The present-day anesthesiologist.

PMID- 15437058
TI  - Psychotherapy in general practice.

PMID- 15437059
TI  - Some causes and treatment of epistaxis.

PMID- 15437060
TI  - A physician views the state vocational rehabilitation division.

PMID- 15437061
TI  - The tumor clinic and the physician.

PMID- 15437062
TI  - Iowa Methodist Hospital clinicopathologic conference; pulmonary and cerebral fat
      embolism with pronounced pulmonary edema.

PMID- 15437063
TI  - Encephalitis.

PMID- 15437064
TI  - Clinical studies of pentaquine, a newer antimalarial agent.

PMID- 15437066
TI  - Current concepts and approaches to cancer research.

PMID- 15437065
TI  - Gold therapy in rheumatoid arthritis.

PMID- 15437067
TI  - Cancer of the colon.

PMID- 15437068
TI  - Newer concepts in the pathogenesis and treatment of congestive heart failure.

PMID- 15437069
TI  - Manifestations of breast cancer.

PMID- 15437070
TI  - Rectal bleeding, causes, management.

PMID- 15437071
TI  - Cancer of the anus and lower rectum.

PMID- 15437072
TI  - The neurologic manifestations of pernicious anemia.

PMID- 15437073
TI  - Acute hemolytic anemia complicating phenylhydrazine therapy.

PMID- 15437074
TI  - ELMER L. Henderson, M. D., President, American Medical Association.

PMID- 15437075
TI  - Some endocrine factors in obstetrics and gynecology.

PMID- 15437076
TI  - Asphyxia neonatorum.

PMID- 15437077
TI  - The role of immature plasma cells, lymphoblasts, and lymphocytes in the formation
      of antibodies, as established in tissue culture experiments.

PMID- 15437078
TI  - Bacteriologic studies of the newer antibiotics: effect of combined drugs on
      microorganisms.

PMID- 15437079
TI  - Metabolism and excretion of alkaline phosphatase: relation to liver function and
      determination of maximal secretory rates of liver.

PMID- 15437080
TI  - Acute disseminated lupus erythematosus; report of a case treated with
      adrenocorticotropic hormone (ACTH) with clinical and metabolic observations and
      autopsy findings.

PMID- 15437081
TI  - The distribution of thiopental in the central nervous system.

PMID- 15437082
TI  - The diuretic action of a coumarin-mercurial compound.

PMID- 15437083
TI  - The P factor and its variants in Caucasians, Negroes, and Chinese.

PMID- 15437084
TI  - The coagulation defect of vitamin K deficiency compared with that caused by
      dicumarol.

PMID- 15437085
TI  - Megaloblastic anemia of pregnancy: response to pteroylglutamic acid after failure
      of response to liver extract and vitamin B12b.

PMID- 15437086
TI  - Allergic reactions from the ingestion or intravenous injection of cane sugar
      (sucrose).

PMID- 15437087
TI  - Protection against diabetes with nicotinamide.

PMID- 15437088
TI  - The plasma levels of nine free amino acids in old men and women.

PMID- 15437089
TI  - The trypsin inhibitor of the urine in health and disease.

PMID- 15437090
TI  - Artificial kidney; elimination of vasodepressor effects due to cellophane.

PMID- 15437091
TI  - Benemid and carinamide: comparison of effect on para-aminosalicylic acid (PAS)
      plasma concentrations.

PMID- 15437092
TI  - Heterophile agglutination variability of erythrocytes from different sheep.

PMID- 15437093
TI  - Observations on the role of pulmonary congestion in the production of edema of
      the lungs.

PMID- 15437094
TI  - Urinary formaldehydogenic corticoids: normal values and observations in
      hypertension.

PMID- 15437095
TI  - A rapid test for the serodiagnosis of syphilis; 6 years' experience and
      improvements.

PMID- 15437096
TI  - Estimation of the level of blood alcohol from analysis of breath.

PMID- 15437097
TI  - A device to determine the time of exposure in the heart cycle of an
      angiocardiogram.

PMID- 15437098
TI  - A rapid semimicro method for the determination of C14.

PMID- 15437099
TI  - A constant-level, boiling water bath.

PMID- 15437100
TI  - A simply constructed halometer.

PMID- 15437101
TI  - The clinical detection of auditory recruitment.

PMID- 15437102
TI  - Rubella congenital inner-ear deafness.

PMID- 15437103
TI  - Studies on the sensory epithelium of the labyrinthine crista ampullaris in
      fishes.

PMID- 15437104
TI  - Clinical and pathological observations of a case of leukaemia with deafness and
      vertigo.

PMID- 15437105
TI  - Two cases of carcinoma of the trachea.

PMID- 15437106
TI  - The problem of hypopharyngeal carcinoma.

PMID- 15437108
TI  - Improvement in the care of the newborn, a resume.

PMID- 15437107
TI  - Dicumarol treatment of myocardial infarction, threatened or actual.

PMID- 15437109
TI  - Ectopic pregnancy.

PMID- 15437110
TI  - Cystectomy and uretero-intestinal anastomosis for cancer of the bladder.

PMID- 15437111
TI  - Transthoracic nephrectomy for metastatic osteogenic sarcoma of the kidney.

PMID- 15437112
TI  - Bronchiogenic carcinoma; present concepts as to diagnosis and treatment.

PMID- 15437113
TI  - Rupture of the musculotendinous cuff of the shoulder.

PMID- 15437114
TI  - The use of prefrontal lobotomy in treating intractable pain with a review of the
      literature.

PMID- 15437115
TI  - Familial polyposis of the colon.

PMID- 15437116
TI  - The 1949 poliomyelitis epidemic.

PMID- 15437117
TI  - Nursing education in Portland's community medical center.

PMID- 15437119
TI  - CLINICO-PATHOLOGICAL exercise; periarteritis nodosa.

PMID- 15437118
TI  - Physical therapy at the Maine General Hospital.

PMID- 15437120
TI  - [Examination of bone marrow; puncture and sternal trepan puncture; normal and
      pathologic myelograms].

PMID- 15437121
TI  - [Allergy in schools and universities of the Southwest].

PMID- 15437122
TI  - [Modern methods in control of diseases transmitted by insects].

PMID- 15437123
TI  - [Recent research in amebiasis; practical consequences].

PMID- 15437124
TI  - [Epidemic vomiting in autumn in infants].

PMID- 15437125
TI  - [A complement of blood sedimentation; formol-gelation of plasma].

PMID- 15437126
TI  - [Whooping cough lung and whooping cough mediastinitis].

PMID- 15437127
TI  - [New data on hemolytic disease of the newborn and of the fetus; the possible role
      of anti-A and anti-B maternal immunization].

PMID- 15437128
TI  - [Epigastric pain in fermentative diarrhea].

PMID- 15437129
TI  - [The dumping syndrome and intolerance to milk].

PMID- 15437130
TI  - [Chloramphenicol in the treatment of typhoid fever].

PMID- 15437131
TI  - [Present treatment of tuberculous meningitis in the adult].

PMID- 15437132
TI  - [Permeability of the meninges during meningitis, particularly during tuberculous
      meningitis].

PMID- 15437133
TI  - [Present problem of congenital syphilis].

PMID- 15437134
TI  - [The clinical forms and treatment of eczema].

PMID- 15437135
TI  - [Effect of sodium para-amino-salicylate on disorders of keratinization].

PMID- 15437136
TI  - [Case of malignant monocytic reticulosis; cutaneous aspects of malignant
      reticulosis; attempted synthesis; classification of reticuloses].

PMID- 15437138
TI  - Common nutritional errors.

PMID- 15437137
TI  - [Therapy of tinea capitis].

PMID- 15437139
TI  - Nutritional errors in old age.

PMID- 15437140
TI  - Common nutritional errors.

PMID- 15437141
TI  - Historic delays in the application of knowledge about the heart.

PMID- 15437142
TI  - Congenital malformation of the heart.

PMID- 15437143
TI  - Nonsurgical congenital heart disease.

PMID- 15437144
TI  - Experiences with surgery for relief of congenital malformation of the heart and
      great vessels.

PMID- 15437146
TI  - Obesity, with special reference to cardiovascular disease.

PMID- 15437145
TI  - Anesthesiology in congenital heart disease.

PMID- 15437147
TI  - Role of the general practitioner in 1950 medicine.

PMID- 15437148
TI  - Tracheo-esophageal anomaly in siblings.

PMID- 15437149
TI  - Typhoid fever treated with chloromycetin; a case report.

PMID- 15437150
TI  - Immunology in hematology.

PMID- 15437151
TI  - Anorectal disease and gastro-intestinal disturbances.

PMID- 15437152
TI  - Congenital absence of the gall bladder.

PMID- 15437153
TI  - Iodo-acetate index in cancer.

PMID- 15437154
TI  - Multiple myeloma; report of a case.

PMID- 15437155
TI  - Banthine in the control of duodenal ulcer.

PMID- 15437156
TI  - Closed brain injuries.

PMID- 15437157
TI  - The clinical use of ballistocardiography.

PMID- 15437158
TI  - A simplified cord tie.

PMID- 15437159
TI  - The manipulative treatment of low back pain.

PMID- 15437161
TI  - Occupational therapy in physical medicine.

PMID- 15437160
TI  - Physical medicine and rehabilitation in the management of hemiplegia in the
      adult.

PMID- 15437162
TI  - Disruption of vaginal wound with evisceration; eighteen months following vaginal
      hysterectomy.

PMID- 15437163
TI  - The general practitioner visits the National Health doctor.

PMID- 15437164
TI  - Teratoma of the ovary in a child.

PMID- 15437165
TI  - The duodenal stump.

PMID- 15437166
TI  - Multiple sclerosis.

PMID- 15437167
TI  - Fluid and electrolyte balance in the management of acute renal insufficiency.

PMID- 15437168
TI  - Hematologic phenomena in acute disseminated lupus erythematosus.

PMID- 15437169
TI  - Some important etiologic factors in breech presentation.

PMID- 15437170
TI  - Relation of adrenal cortex to electrolyte and water metabolism.

PMID- 15437171
TI  - The adrenal cortex and the "diseases of adaptation".

PMID- 15437172
TI  - The relationship of the adrenal cortex to homeostasis.

PMID- 15437173
TI  - Surgical lesions of the stomach.

PMID- 15437175
TI  - Subacute bacterial endocarditis.

PMID- 15437174
TI  - The value of the anesthesiologist to the various fields of medicine and surgery.

PMID- 15437176
TI  - Causes of sterility in the male.

PMID- 15437177
TI  - Modern advances in anesthesiology.

PMID- 15437178
TI  - CLINICAL pathologic conference; rheumatic pneumonia; acute rheumatic fever; acute
      rheumatic disease, pancarditis, with involvement of the mitral and aortic valves.

PMID- 15437179
TI  - Lipoid pneumonia of upper lobe of right lung.

PMID- 15437180
TI  - The growth of normal plant tissue in vitro as affected by chemical carcinogens
      and plant growth substances. II. The cytology of the carrot-root tissue.

PMID- 15437181
TI  - Histopathology of estrogen-induced tumors in guinea pigs.

PMID- 15437182
TI  - Production of malignancy in vitro. X. Continued description of cells at the glass
      interface of the cultures.

PMID- 15437183
TI  - Production of malignancy in vitro. XI. Further results from reinjection of in
      vitro cell strains into strain C3H mice.

PMID- 15437184
TI  - A comparative study of the morphology and glucuronidase activity in 44
      gastrointestinal neoplasms.

PMID- 15437185
TI  - Inhibition of sea-urchin egg cleavage by a series of substituted carbamates.

PMID- 15437186
TI  - Factors in the development of spontaneous mammary gland tumors in agent--free
      strain C3Hb mice.

PMID- 15437187
TI  - Attempt to detect a mammary tumor-agent in strain C mice by x-radiation.

PMID- 15437188
TI  - Studies on fatty acid oxidation by normal and neoplastic liver.

PMID- 15437189
TI  - Comparative studies of liver glucuronidase activity in inbred mice.

PMID- 15437190
TI  - Studies in epilepsy; the significance of "spontaneous" abnormalities in brain
      wave patterns as observed during interview with epileptic patients.

PMID- 15437191
TI  - Mild manic-depressive psychosis, depressive type: psychiatric and clinical
      significance.

PMID- 15437192
TI  - Remission as a feature in torulosis.

PMID- 15437193
TI  - Amnesia for left limbs and loss of interest and attention in left fields of
      vision.

PMID- 15437194
TI  - Sodium amytal as a causative factor in some cases of prolonged insulin coma.

PMID- 15437195
TI  - Seizures, head injuries and litigants.

PMID- 15437197
TI  - Unilateral prefrontal lobotomy for the relief of somatic pain.

PMID- 15437196
TI  - The range of psychoanalytic therapy.

PMID- 15437198
TI  - A comparative study of antihistaminic and other drugs in Parkinson's disease.

PMID- 15437199
TI  - Disc degeneration: a distinct clinical entity.

PMID- 15437200
TI  - Hemorrhage into hemangiomatous cerebellar cyst.

PMID- 15437201
TI  - Post-infectious encephalomyelitis and multiple sclerosis; the significance of
      perivenous encephalomyelitis.

PMID- 15437202
TI  - Frontal lobotomy; neuroanatomical observations.

PMID- 15437203
TI  - Xanthomas of the choroid plexus in man.

PMID- 15437204
TI  - Neuropathological findings in phenyl-pyruvic oligophrenia (phenyl-ketonuria).

PMID- 15437205
TI  - Cerebral contusion in accidental electrocution; pathologic study of a case.

PMID- 15437206
TI  - Primary mesenchymal tumors of the brain, so-called reticulum cell sarcoma; report
      of 5 cases.

PMID- 15437207
TI  - Changes in the arteriae nervorum in peripheral nerve injuries in man.

PMID- 15437208
TI  - Uremia encephalitis; a case report.

PMID- 15437209
TI  - Combined staining of iron and fat in frozen sections.

PMID- 15437210
TI  - Chronic essential fatty acid deficiency in mice.

PMID- 15437211
TI  - Urinary and fecal elimination of B6 and 4-pyridoxic acid on three levels of
      intake.

PMID- 15437212
TI  - The effect of supplementation of high corn diets on rat reproduction and
      lactation.

PMID- 15437213
TI  - On the relative nutritional efficiency of sucrose and glucose in the albino rat.

PMID- 15437214
TI  - Vitamin B12 production by microorganisms isolated from poultry house litter and
      droppings.

PMID- 15437215
TI  - Utilization of vitamin A by turkey poults. I. Crystalline carotene, crystalline
      vitamin A acetate and "black cod" liver oil.

PMID- 15437216
TI  - A comparison of techniques used in digestibility studies with dairy cattle.

PMID- 15437217
TI  - Studies of dietary restriction and rehabilitation. I. Interrelationships among
      the fat, water content and specific gravity of the albino rat.

PMID- 15437218
TI  - The N balance index of low-valine amino acid mixtures and of whole egg protein in
      the adult rat.

PMID- 15437219
TI  - Studies on carotenoid metabolism. X. The site of conversion of carotene to
      vitamin A in the chick.

PMID- 15437220
TI  - The use of chromic oxide as an index for determining the digestibility of a diet.

PMID- 15437221
TI  - The crippled lung.

PMID- 15437222
TI  - Indications for and results of keratoplasty.

PMID- 15437223
TI  - Differential diagnosis of a red eye.

PMID- 15437224
TI  - Goniotomy in congenital glaucoma.

PMID- 15437225
TI  - Anticoagulants.

PMID- 15437227
TI  - A new cestode, Raillietina (R) multitesticulata n. sp. from the red howler
      monkey.

PMID- 15437226
TI  - Henneguya vitiensis n.sp., a myxosporidian from a Fijian marine fish, Leiognathus
      fasciatus (Lacepede, 1803).

PMID- 15437228
TI  - A new species of Triganodistomum (Trematoda: Lissorchiidae) from the Sacramento
      sucker, Catostomus occidentalis Ayres.

PMID- 15437229
TI  - The mouth parts of the adult female tropical rat mite, Bdellonyssus bacoti
      (Hirst, 1913) Fonseca, 1941 [-Liponissus bacoti (Hirst)], with observations on
      the feeding mechanism.

PMID- 15437230
TI  - Two new species of ticks from Ceylon (Acarina: Ixodidae).

PMID- 15437231
TI  - Laboratory studies of combinations of piperonyl cyclonene, piperonyl butoxide,
      pyrethrins, and rotenone for the control of ticks on dogs.

PMID- 15437232
TI  - Observations on ectoparasites of some small mammals in Everglades National Park
      and Hillsborough County, Florida.

PMID- 15437233
TI  - The comparative growth cycle of different strains of Endamoeba histolytica in
      transparent medium and of the same strain in different media.

PMID- 15437234
TI  - Experimental studies on trichomoniasis: 1. The pathogenicity of trichomonad
      species for mice.

PMID- 15437235
TI  - Two new species of Trichuris from North America, with redescriptions of Trichuris
      opaca and Trichuris leporis (Nematoda: Aphasmidia).

PMID- 15437236
TI  - A new genus and species of trombiculid mite from Burma (Acarina).

PMID- 15437237
TI  - Parasitictodora hancocki n. gen., n. sp. (Trematoda: Heterophyidae), with
      observations on its life cycle.

PMID- 15437238
TI  - Studies on tapeworm physiology. V. Further observations on the maturation of
      Schistocephalus solidus (Diphyllobothriidae) under sterile conditions in vitro.

PMID- 15437239
TI  - Studies on cestode metabolism. I. Glycogen metabolism in Schistocephalus solidus
      in vivo.

PMID- 15437241
TI  - A survey of the epidemiology of diphtheria in north-west Europe and North America
      in the period 1920-1946.

PMID- 15437240
TI  - Retrofection in oxyuriasis. Conclusions.

PMID- 15437242
TI  - Type-specific agglutinins in Corynebacterium diphtheriae infections.

PMID- 15437243
TI  - Serological types of Corynebacterium diphtheriae in Australia.

PMID- 15437244
TI  - Infectious mononucleosis: report of a case with autopsy.

PMID- 15437245
TI  - The renal appearances in the microscopic form of periarteritis nodosa.

PMID- 15437246
TI  - A study of the changes in the brain in experimental internal hydrocephalus.

PMID- 15437248
TI  - A spontaneous carcinoma of the skin of a ferret (Mustela furo L.).

PMID- 15437247
TI  - The retention and excretion of radioactive strontium and yttrium (Sr89, Sr90 and
      Y 90) in the healthy rabbit.

PMID- 15437249
TI  - Streptococcal endocarditis in lambs.

PMID- 15437250
TI  - The presence of cold haemolysins in sera containing cold haemagglutinins.

PMID- 15437251
TI  - Early tissue reactions to a South African strain of Histoplasma capsulatum in
      laboratory animals.

PMID- 15437252
TI  - Note on the isolation of Cryptococcus neoformans from a sample of milk.

PMID- 15437253
TI  - The sensitivity of glycine-resistant organisms to the bactericidal action of
      serum.

PMID- 15437254
TI  - Anthony Mavrogordato.

PMID- 15437255
TI  - Intussusception in infants and children; analysis of 152 cases with a discussion
      of reduction by barium enema.

PMID- 15437256
TI  - Virus hepatitis in infancy.

PMID- 15437257
TI  - Body size norms for children four to eight years of age.

PMID- 15437258
TI  - Treatment of hydrocephalus by ventriculomastoidostomy.

PMID- 15437259
TI  - Transposition of viscera in siblings.

PMID- 15437260
TI  - Combined immunization of tuberculous children against diphtheria, pertussis, and
      tetanus.

PMID- 15437261
TI  - The skeletal lesions of leukemic children treated with aminopterin.

PMID- 15437262
TI  - Funnel chest: its cause, effects, and treatment.

PMID- 15437263
TI  - The variability of the electrocardiogram in congenital tricuspid atresia.

PMID- 15437264
TI  - A clinical trial with chloromycetin in Shigella dysenteriae (Sonne); a report of
      three cases.

PMID- 15437265
TI  - Orthopedic treatment of the pigeon-toed child.

PMID- 15437266
TI  - High ventricular septal defect and slight dextroposition of the aorta
      (Eisenmenger complex) associated with deformed aortic value simulating patent
      ductus arteriosus.

PMID- 15437267
TI  - Arterial thrombosis in the newborn infant.

PMID- 15437268
TI  - Some recent advances in poliomyelitis.

PMID- 15437269
TI  - Feeble-mindedness and pseudofeeble-mindedness.

PMID- 15437270
TI  - Diabetes mellitus in infants and children. I. Information for parents.

PMID- 15437271
TI  - A comparison of "symptomatic treatment," gamma globulin, and penicillin in the
      treatment of scarlet fever.

PMID- 15437272
TI  - Aureomycin in the treatment of pertussis: a preliminary report.

PMID- 15437273
TI  - Resuscitation of the newborn infant; use of the positive pressure oxygen-air
      lock.

PMID- 15437274
TI  - Incomplete pancreatic deficiency in cystic fibrosis of the pancreas.

PMID- 15437275
TI  - Cerebral birth injury in retrospect.

PMID- 15437276
TI  - The glycemic response of the newborn infant to epinephrine administration: a
      preliminary report.

PMID- 15437277
TI  - A note on the treatment of diaper rash with alkyl-dimethyl-benzyl-ammonium
      chlorides (roccal).

PMID- 15437278
TI  - Measure of immunologic responses to an improved preparation of diphtheria and
      tetanus toxoids (alum precipitated) combined with pertussis vaccine.

PMID- 15437279
TI  - Premature mortality; an analysis of 518 cases of prematurity with a comparison of
      Negro and white races.

PMID- 15437280
TI  - Dehydrated banana in the dietetic management of diarrheas of infancy.

PMID- 15437281
TI  - Purpura following exposure to DDT.

PMID- 15437282
TI  - High gastrointestinal obstruction in the newborn infant: a radiological
      interpretation.

PMID- 15437283
TI  - Congenital choledochus cyst; review of the literature and a case report with one
      year postoperative follow-up.

PMID- 15437284
TI  - Trichobezoar in a four-year-old child.

PMID- 15437285
TI  - Atresia of the pulmonary artery with intact interventricular septum.

PMID- 15437286
TI  - Changing philosophies in cleft palate management.

PMID- 15437287
TI  - Childhood schizophrenia.

PMID- 15437288
TI  - The pharmacology of thiomerin.

PMID- 15437289
TI  - Analgesic action of 3-hydroxy-N-methyl morphinan hydrobromide (dromoran).

PMID- 15437290
TI  - The fate of aminopyrine (pyramidon) in man and methods for the estimation of
      aminopyrine and its metabolites in biological material.

PMID- 15437291
TI  - Species differences in susceptibility to methemoglobin formation.

PMID- 15437292
TI  - Histamine antagonists. XV. Comparative experimental studies of certain
      antihistaminic compounds.

PMID- 15437293
TI  - Evaluation of agents with thyroxine-inhibiting effects.

PMID- 15437294
TI  - Evaluation of curarizing drugs in man. II. Analysis of response curves and
      effects of repeated administration of d-tubocurarine, dimethyl-d-tubocurarine and
      decamethylene-bis (trimethylammonium bromide).

PMID- 15437295
TI  - Evaluation of curarizing drugs in man. III. Antagonism to curarizing effects of d
      tubocurarine and decamethylene-bis(trimethylammonium bromide).

PMID- 15437296
TI  - The pharmacology of terramycin.

PMID- 15437297
TI  - Pharmacology of beta-diethylaminoethyl xanthene-9-carboxylate methobromide
      (banthine) and chloride.

PMID- 15437298
TI  - The antagonism between acetylcholine and the curare alkaloids, d-tubocurarine, c
      curarine-I, c-toxiferine-II and beta-erythroidine in the rectus abdominis of the
      frog.

PMID- 15437300
TI  - A new apparatus and procedure for continuous registration of changes in coronary
      flow concurrently with changes in heart contractions.

PMID- 15437299
TI  - Studies on the inter-relationships of certain cholinergic compounds. III. The
      reactions between 3-acetoxy phenyltrimethylammonium methylsulfate, 3-hydroxy
      phenyltrimethylammonium bromide and cholinesterases.

PMID- 15437301
TI  - Effect of epinephrine, aminophylline, nitroglycerine and papaverine on coronary
      inflow and on heart contraction, as recorded concurrently.

PMID- 15437302
TI  - Activity of some newer spasmolytic agents on the biliary tract of man; a
      comparative study of isopropyl-norepinephrine, adiphenine hydrochloride,
      methylamino-iso-octene and khellin.

PMID- 15437303
TI  - Studies on the pharmacology and toxicology of di-alpha-1,3-dimethyl-4-propionoxy
      piperidine (Nu-1196).

PMID- 15437304
TI  - A comparison of the actions of meperidine, Nu-1196, methadone, morphine, Nu-2206,
      and metopon upon the intestine and uterus.

PMID- 15437305
TI  - The effect of some anticonvulsant agents upon agene-induced convulsions in dogs.

PMID- 15437306
TI  - Metabolism of myanesin (3-(O-toloxy)-1,2-propanediol).

PMID- 15437307
TI  - Structure-activity relationships of acetylcholine and quaternary ammonium ions.

PMID- 15437308
TI  - Coronary dilator action. I. Quantitative assay in the intact dog.

PMID- 15437309
TI  - d-Tubocurarine chloride and enzyme activity.

PMID- 15437310
TI  - Some pharmacological properties of a series of acetamidines and propionamidines.

PMID- 15437311
TI  - The potentiating action of certain xanthine derivatives on gastric acid secretory
      responses in the dog.

PMID- 15437312
TI  - Effect of carinamide (4-carboxyphenyl-methane sulfonamilide) on the metabolism of
      thiopental in mice.

PMID- 15437313
TI  - The effects of thiopental sodium, chloroform, and diethyl ether on the metabolism
      and toxicity of procaine.

PMID- 15437314
TI  - Studies on the toxicity and pharmacological action of octamethyl
      pyrophosphoramide (OMPA; Pestox III).

PMID- 15437315
TI  - The cardiac action of Helleborus glycosides and their aglycones.

PMID- 15437316
TI  - A quantitative study blood pressure response to cardiovascular drugs and their
      antagonists.

PMID- 15437317
TI  - The physiological disposition of dicumarol in man.

PMID- 15437318
TI  - A comparison of procaine and tridiurecaine.

PMID- 15437319
TI  - The mechanism of apnea following intravenous injection of various antihistaminic
      compounds; its relation to their chemical structure.

PMID- 15437320
TI  - Absorption, distribution, and excretion of sodium fluoroacetate (1080) in rats.

PMID- 15437321
TI  - Pharmacology of a new autonomic ganglion blocking agent, 2,6-dimethyl-1,1-diethyl
      piperidinium bromide (SC-1950).

PMID- 15437322
TI  - Potentiation of the antimalarial activity of sulfadiazine by 2,4-diamino-5
      aryloxypyrimidines.

PMID- 15437323
TI  - Toxicity, antipyretic and analgesic studies on 39 compounds including aspirin,
      phenacetin and 27 derivatives of carbazole and tetrahydrocarbazole.

PMID- 15437324
TI  - The neuromuscular blocking action of succinylcholine (diacetylcholine).

PMID- 15437325
TI  - The choleretic potencies of some synthetic compounds.

PMID- 15437326
TI  - Pharmacology of N-(2-furfuryl)-N-(2-pyridyl)-N',N'-dimethylethylenediamine
      fumarat (methafurylene fumarate). I. Antihistaminic properties of this compound
      and its 5-chloro and 5-bromo derivatives.

PMID- 15437327
TI  - Pharmacology of N-(2-furfuryl)-N-(2-pyridyl)-N',N'-dimethylethylenediamine
      fumarate (methafurylene fumarate II. Toxicological studies.

PMID- 15437328
TI  - Functional characteristics of transport mechanisms.

PMID- 15437329
TI  - Recent contributions to the pharmacology of bis(2-haloethyl) amines and sulfides.

PMID- 15437330
TI  - Carbon monoxide.

PMID- 15437331
TI  - Addiction to analgesics and barbiturates.

PMID- 15437332
TI  - The structure and properties of aqueous solutions of soap.

PMID- 15437333
TI  - The bactericidal activity of phenols in aqueous solutions of soap; the solubility
      of a water-insoluble phenol in aqueous solutions of soap.

PMID- 15437334
TI  - The chemistry of anti-pernicious anaemia factors; benziminazole glycosides; the
      preparation and properties of some o-nitroaniline glycosides.

PMID- 15437336
TI  - [Considerations on toxicosis of infants].

PMID- 15437335
TI  - [Cranio-cerebral traumatisms].

PMID- 15437337
TI  - [Some new procedures used in the treatment of pulmonary tuberculosis;
      extraperiosteal pneumothorax].

PMID- 15437338
TI  - [Spontaneous premunition against tuberculosis has not, in New Caledonia and
      Guiana, given protection against leprosy].

PMID- 15437339
TI  - [Cranio-cerebral traumatisms; closed wounds].

PMID- 15437340
TI  - [Childhood and delinquency].

PMID- 15437341
TI  - [Hormonal determination of mammary development].

PMID- 15437342
TI  - [The first decade of life; neurological examination].

PMID- 15437343
TI  - [The surgical moment in pulmonary tuberculosis].

PMID- 15437344
TI  - [Fight against alcoholism; a new product: antabuse].

PMID- 15437345
TI  - [Some new procedures used in the treatment of pulmonary tuberculosis].

PMID- 15437346
TI  - [Intolerance: infant's intolerance to milk].

PMID- 15437347
TI  - [Penicillin in syphilis therapy].

PMID- 15437348
TI  - [Surgical ascites in women].

PMID- 15437349
TI  - [Infiltration of the preaortic plexus].

PMID- 15437350
TI  - [Unnecessary appendicectomies].

PMID- 15437351
TI  - [The surgeon's role in the treatment of angina pectoris].

PMID- 15437352
TI  - [Alopecia].

PMID- 15437353
TI  - [Prophylaxis and treatment of puerperal infection].

PMID- 15437354
TI  - [Chloromycetin in the treatment of typhoid and paratyphoid fevers].

PMID- 15437355
TI  - [Scapulohumeral periarthritis].

PMID- 15437356
TI  - [New bismuth preparation].

PMID- 15437357
TI  - [Sulfones in the treatment of tuberculosis].

PMID- 15437358
TI  - [Diagnosis of torticollis].

PMID- 15437360
TI  - [Silicosis and pneumoconiosis].

PMID- 15437359
TI  - [Nail biting and thumb sucking in the child].

PMID- 15437361
TI  - [Rational prophylaxis of typhoid fever].

PMID- 15437362
TI  - [The electro-physiological basis and technic of electroshock].

PMID- 15437363
TI  - [Diets and obesity].

PMID- 15437364
TI  - [Tissue therapy; Filatov's method].

PMID- 15437365
TI  - [Therapeutic use of narcosis].

PMID- 15437366
TI  - [Treatment of acute meningitis].

PMID- 15437367
TI  - [Atypical pneumonias].

PMID- 15437368
TI  - [Classic and modern tests for medical examination of the liver].

PMID- 15437369
TI  - [Organized thromboses of the cardiac cavity].

PMID- 15437370
TI  - [Duodenal occlusion of the newborn].

PMID- 15437371
TI  - [Practical considerations on dolichocolon and megacolon in children].

PMID- 15437372
TI  - [Medical treatment of otospongiosis].

PMID- 15437373
TI  - [Mental alienation is not a matter of medicine].

PMID- 15437374
TI  - [Surgery under the control of electroencephalography in essential epilepsy].

PMID- 15437375
TI  - [Diabetes and heredity; a genealogy of diabetics].

PMID- 15437376
TI  - [What you should know about aureomycin].

PMID- 15437377
TI  - [Cancer of the prostate; present problems of therapy].

PMID- 15437378
TI  - [Nerve opotherapy in the treatment of gastro-duodenal ulcers].

PMID- 15437379
TI  - [Menstrual disorders].

PMID- 15437380
TI  - [Virus urethritis].

PMID- 15437381
TI  - [The protein formula of plasma and its clinical applications].

PMID- 15437382
TI  - [The chronic forms of gonococcic rheumatism and their treatment].

PMID- 15437383
TI  - [Primary complex of tuberculosis].

PMID- 15437384
TI  - [Metrorrhagias due to lesions of the uterine arteries (arterial aneurysms)].

PMID- 15437385
TI  - [Aureomycin: use in the treatment of zoster].

PMID- 15437386
TI  - [Fatal cases of provoked abortion].

PMID- 15437387
TI  - [Raynaud's disease].

PMID- 15437388
TI  - [Cutaneous pigmentation and Riehl's melanosis].

PMID- 15437389
TI  - [Psychosomatic medicine].

PMID- 15437390
TI  - [Treatment of acute leukosis of children].

PMID- 15437391
TI  - [Palliative treatment of inoperable gastric cancer: autovaccination by gastric
      juice].

PMID- 15437392
TI  - [New treatment of nephritic colic: intradermal injection of distilled water].

PMID- 15437393
TI  - [Surgical treatment of epilepsy].

PMID- 15437394
TI  - [Preganglionic sympathectomy; its anatomic principle; its technic].

PMID- 15437395
TI  - [Disorders of glycoregulation after gastrectomy].

PMID- 15437396
TI  - [Case of polioencephalitis, bulbar form of Haine-Medin disease].

PMID- 15437397
TI  - [Liver, folic acid, vitamin B12].

PMID- 15437398
TI  - [Treatment of habitual abortion by synthetic estrogens].

PMID- 15437399
TI  - [Cryptogenetic intestinal hemorrhages of the infant].

PMID- 15437400
TI  - [The neuro-mental prognosis of a premature infant of 860 gr..].

PMID- 15437401
TI  - [Pyorrhea and colitis].

PMID- 15437402
TI  - [What one should know about chloromycetin].

PMID- 15437403
TI  - [The danger of certain antipyretics to the child].

PMID- 15437404
TI  - [Evolution of naevi].

PMID- 15437405
TI  - [Insomnia and its treatment].

PMID- 15437406
TI  - [Some practical considerations concerning the treatment of tumors of the
      tonsils].

PMID- 15437407
TI  - [Perfusion through the bone marrow in infants].

PMID- 15437408
TI  - [Epicondylalgie or tennis elbow].

PMID- 15437409
TI  - [Diagnosis of hemoglobinuria].

PMID- 15437410
TI  - [Treatment of bartholinitis].

PMID- 15437411
TI  - [Hormonal influence on the vitality of growth of hair].

PMID- 15437412
TI  - [A new disease: cat disease or bird disease].

PMID- 15437413
TI  - [How to treat and prevent untoward effects of spinal anesthesia].

PMID- 15437414
TI  - [Intestinal invagination of the infant].

PMID- 15437415
TI  - [Facial routes of infection of the primary complex].

PMID- 15437416
TI  - [Streptomycin therapy of tuberculosis in pregnancy].

PMID- 15437417
TI  - [Hyperfolliculinism and the pancreas].

PMID- 15437418
TI  - [Practical advice in the treatment of Pouteau's fracture].

PMID- 15437420
TI  - [Classification of chronic evolutive polyarthritis].

PMID- 15437419
TI  - [A case of Brown-Sequard syndrome].

PMID- 15437421
TI  - [Note on the intellectual fatigue of adolescents and thinkers].

PMID- 15437422
TI  - [Rhinitis; simplified nosography].

PMID- 15437423
TI  - [Cancer of the colon].

PMID- 15437424
TI  - [Formulation of external medicaments in dermatology].

PMID- 15437425
TI  - [High temperature of the newborn].

PMID- 15437426
TI  - [Heliotraumatism].

PMID- 15437427
TI  - [Formulation of external medicaments in dermatology].

PMID- 15437428
TI  - [The sexual life of the woman].

PMID- 15437430
TI  - [Transitory pulmonary condensations].

PMID- 15437429
TI  - [Precocious puberty].

PMID- 15437431
TI  - [Gout].

PMID- 15437432
TI  - [The danger of abuse of estrogens].

PMID- 15437433
TI  - [What you have to know about bacitracin].

PMID- 15437434
TI  - [Menstrual cycle].

PMID- 15437435
TI  - [Compression of the spinal cord].

PMID- 15437436
TI  - [Technique of infiltration of the pelvic sympathetic nerves].

PMID- 15437437
TI  - [Metrorrhagia after menopause].

PMID- 15437438
TI  - [Post-partum endocrine disorders].

PMID- 15437439
TI  - [Subjects for discussion].

PMID- 15437440
TI  - [Mutual relations of tuberculosis and menstruation].

PMID- 15437441
TI  - [Functional disorders and organic disease of the gallbladder and cystic bile
      duct].

PMID- 15437442
TI  - Evaluation of form-level in the Rorschach.

PMID- 15437443
TI  - Psychological report of the Cyprus Psychiatric Mission.

PMID- 15437444
TI  - Painting and drawing in personality assessment.

PMID- 15437445
TI  - Diagnostic testing in a case of latent schizophrenia.

PMID- 15437446
TI  - The latency of latent schizophrenia.

PMID- 15437447
TI  - The Picture Frustration Study as a predictor of overt aggression.

PMID- 15437448
TI  - The effect of situational factors on the TAT; a note on the TAT's of two Nazi
      leaders.

PMID- 15437449
TI  - The concept of integration and the Rorschach test as a measurement of personality
      integration.

PMID- 15437450
TI  - [Oral and sign language].

PMID- 15437451
TI  - [Syntax analysis and psychological analysis].

PMID- 15437452
TI  - [Functional concept of linguistic facts].

PMID- 15437453
TI  - [Structural role of word order].

PMID- 15437455
TI  - [Concept of the verb].

PMID- 15437454
TI  - [Word order in modern French].

PMID- 15437456
TI  - [Problem of verb-noun opposition].

PMID- 15437458
TI  - [Active and middle forms of the verb].

PMID- 15437457
TI  - [Two verb-noun oppositions].

PMID- 15437459
TI  - [Problem of active and passive of verb].

PMID- 15437460
TI  - [The noun and the verb in Roumanian].

PMID- 15437462
TI  - [Objective categories].

PMID- 15437461
TI  - [Linguistic expression of the concept of motion].

PMID- 15437463
TI  - [Meaning of the pronoun "nous" (we) in French].

PMID- 15437464
TI  - [Functional and intrinsic value of the preposition "en" in modern French].

PMID- 15437465
TI  - [Radiographic appearance of congenital syphilis of the bones].

PMID- 15437466
TI  - [Altered dimensions and abnormal form of the optic canal as a predisposing factor
      in diseases of the optic nerve].

PMID- 15437467
TI  - [Tomography of the base of the skull in the living subject].

PMID- 15437468
TI  - [Study of the vascular action of short waves by means of a radioisotope].

PMID- 15437469
TI  - [Pulmonary agenesis with digestive symptoms in an infant].

PMID- 15437470
TI  - [Diverticulum of the greater curvature of the prepyloric antrum of the stomach].

PMID- 15437471
TI  - [Case of voluminous retrosternal diaphragmatic hernia of traumatic origin].

PMID- 15437472
TI  - [Cholecystoduodenal fistula].

PMID- 15437473
TI  - [Abnormality of the carpus; frequency].

PMID- 15437474
TI  - [Lethal irradiation of the mouse by X and gamma rays; attempted therapy].

PMID- 15437475
TI  - [Short-distance roentgenotherapy (contact roentgenotherapy)].

PMID- 15437476
TI  - [Simultaneous use of the mobile and fixed antidiffusing grill].

PMID- 15437477
TI  - [Use of pitressin].

PMID- 15437478
TI  - [The Sans-Porcher polytome].

PMID- 15437479
TI  - [Geiger counters].

PMID- 15437480
TI  - [Not Available].

PMID- 15437481
TI  - [Not Available].

PMID- 15437482
TI  - [Olisthesic scoliosis due to aplasia of one sacral articular].

PMID- 15437483
TI  - [Bronchography with a water-soluble iodine contrast medium].

PMID- 15437484
TI  - [20 years of pituitary radiotherapy].

PMID- 15437486
TI  - [Apparatus for wave lengths imposed by the Atlantic City agreement].

PMID- 15437485
TI  - [Use of radioactive carbon 60 in radium therapy of cancer].

PMID- 15437487
TI  - [Anatomo-radiologic study of the heart].

PMID- 15437488
TI  - [Effect of roentgen irradiation on the reticuloendothelial system; experimental
      research].

PMID- 15437489
TI  - [Radiotherapy of scapulohumeral periarthritis].

PMID- 15437491
TI  - [Radiological study of the skeletal axis of cephalic monsters; relation of this
      abnormality to the Klippel-Feil syndrome].

PMID- 15437490
TI  - [Radiological signs of Banti's disease].

PMID- 15437492
TI  - [Simple radiographic technic for detecting conjugate foramina of the cervical
      vertebral column].

PMID- 15437493
TI  - [Choice of optimum constants for radiography of the lungs].

PMID- 15437494
TI  - [Modern short-wave and diathermo-coagulation apparatus].

PMID- 15437495
TI  - [The vallecular sign and its interpretation].

PMID- 15437496
TI  - [Radiological technic and results of pneumoretroperitoneum].

PMID- 15437497
TI  - [Case of skull fracture].

PMID- 15437498
TI  - [Apparatus for immobilizing the head].

PMID- 15437499
TI  - [Curious modifications of electric reactions during Steinert's disease].

PMID- 15437500
TI  - [Tomographic study of the aorta and the left pulmonary artery in the course of
      various cardiovascular diseases].

PMID- 15437501
TI  - [Exclusion of the gallbladder in biliary dystonias; its semiological and
      prognostic value].

PMID- 15437503
TI  - [Importance of digital examination of the rectum in electroradiology].

PMID- 15437502
TI  - [Tomography of bones].

PMID- 15437504
TI  - [Half-centimeter grill].

PMID- 15437505
TI  - [Radiographic films of intracardiac catheters].

PMID- 15437506
TI  - [Lumbar calcifications and ureteral calculi].

PMID- 15437507
TI  - [Disorders of the body fluids in cancer and their evolution in the course of
      radiotherapy].

PMID- 15437508
TI  - [Indications for radiotherapy in biliary dystonia; 8 cases of which 5 were
      verified surgically].

PMID- 15437509
TI  - [Intensity of solar radiation at high altitude and on the Mediterranean shore].

PMID- 15437510
TI  - [Urgency of roentgenotherapy in acute ossifying periarthritis].

PMID- 15437511
TI  - [Invagination seen 50 minutes after inception and reduced by enema].

PMID- 15437512
TI  - [Diaphragmatic hernia and volvulus of the stomach].

PMID- 15437513
TI  - [Films of the lung taken with and without a movable vertical grill].

PMID- 15437514
TI  - [Results of a year's tomographic practice in pneumophthisiology].

PMID- 15437515
TI  - [Formation of image in tomography; theory and practice].

PMID- 15437517
TI  - [Tomography of nodular lesions of the lung].

PMID- 15437516
TI  - [Duration of the formation of renal calculi].

PMID- 15437518
TI  - [Diagnosis of enlargements of the optic canal; a tumor of the optic nerve
      spreading to the chiasma].

PMID- 15437519
TI  - [Simultaneous tomography by the Manoel de Abreu method].

PMID- 15437520
TI  - [Cancer of the lung in a 5-year-old child with involvement of cervical and
      axillary lymph nodes].

PMID- 15437521
TI  - [New case of diaphragmatic eventration].

PMID- 15437522
TI  - [Epithelioma of the piriform sinus detected by radioscopy].

PMID- 15437523
TI  - [Orientation by radiography for the management of coxitis].

PMID- 15437524
TI  - The old soldier.

PMID- 15437525
TI  - Recruitment of officers in the United States Army Medical Department.

PMID- 15437526
TI  - Career management in the United States Army Medical Department.

PMID- 15437527
TI  - Medical arrangements in Malaya during the emergency 1948-49.

PMID- 15437528
TI  - The medical services in an armoured division.

PMID- 15437529
TI  - Some notes on service in West Africa command.

PMID- 15437530
TI  - Scientific methods and some service problems; conference of Medical Research
      Council workers and service and industrial medical officers.

PMID- 15437531
TI  - Recent advances in the treatment of bilharziasis; miracil D.

PMID- 15437533
TI  - Recent results in virus research.

PMID- 15437532
TI  - Comparative study of sulphonamides in treatment of infantile dyspepsia.

PMID- 15437534
TI  - Tumours of the adrenal medulla and the sympathetic nervous system and the
      associated systemic disturbances.

PMID- 15437535
TI  - A preliminary report on "wia" (a new bismuth-arsenical compound) in the treatment
      of amoebic dysentery.

PMID- 15437536
TI  - Vitamin A content of gamoose butter fat, and its variation with the method of
      preparation of "samna".

PMID- 15437537
TI  - Approximate portal circulation time (P.C.T.) a new method of assay of liver
      function.

PMID- 15437538
TI  - Tissue immunity.

PMID- 15437539
TI  - Gerontology or the problems of old age.

PMID- 15437540
TI  - The intervertebral discs and sciatica.

PMID- 15437541
TI  - Persian interlude.

PMID- 15437542
TI  - Dermatological experiences in a training ship.

PMID- 15437543
TI  - Comparisons of the naval, military, R.A.F. and civil medical services with
      private practice.

PMID- 15437544
TI  - Headaches, dizzy spells and blackouts (and the gastric stomach).

PMID- 15437546
TI  - A fibrous growth in relation to a permanent upper canine.

PMID- 15437545
TI  - Notes on an influenza outbreak in a closed community.

PMID- 15437547
TI  - A case of familial paralysis.

PMID- 15437548
TI  - An optimum school health program.

PMID- 15437549
TI  - A directive from history.

PMID- 15437550
TI  - OKLAHOMA School of the Air throws the spotlight on health.

PMID- 15437551
TI  - The mentally ill child.

PMID- 15437552
TI  - Cooperative activity for community health: the Waterbury program.

PMID- 15437553
TI  - [Cardiovascular accidents following use of testosterone implants].

PMID- 15437555
TI  - [Pulmonary ventilation disorders in children].

PMID- 15437554
TI  - [New treatments for cystitis following nephrectomy for tuberculosis].

PMID- 15437556
TI  - [Identification of the pathogenic mechanism and of the symptomatology of
      gastrointestinal ulcers].

PMID- 15437557
TI  - [2 Cases of sigmoid volvulus].

PMID- 15437558
TI  - [Hydronephrosis with gastrointestinal symptoms].

PMID- 15437559
TI  - [Evolution of a bone metastasis of bilateral breast cancer].

PMID- 15437561
TI  - The purpose of a state medical society.

PMID- 15437560
TI  - [Grave acute anemia with agranulocytosis due to excessive doses of cryogenine and
      pyramidon in a 19 month old child].

PMID- 15437562
TI  - Subacute bacterial endocarditis; the use of hyaluronidase as a supplement to
      penicillin treatment in bacterial endocarditis.

PMID- 15437564
TI  - The rise, fall, and resurrection of tonsillectomy.

PMID- 15437563
TI  - Meningitis due to Pseudomonas pyocyanea: report of a case successfully treated
      with dihydrostreptomycin and sulfadiazine.

PMID- 15437565
TI  - Chemotherapy of malignancy.

PMID- 15437566
TI  - Epitheliomas of the face and scalp.

PMID- 15437567
TI  - Surgical lesions of the small bowel.

PMID- 15437568
TI  - VANDERBILT University School of Medicine medical staff conference.

PMID- 15437569
TI  - JOHN Gaston Hospital clinical pathological conference; papillomatosis of larynx,
      trachea, bronchi and pulmonary alveoli.

PMID- 15437570
TI  - Primary intrathoracic neurogenic tumors.

PMID- 15437571
TI  - Tumors of the thymus.

PMID- 15437572
TI  - Syphilis of the esophagus.

PMID- 15437573
TI  - Cavernostomy for residual cavity after thoracoplasty; early closure of
      cavernostomy sinuses under streptomycin protection.

PMID- 15437574
TI  - Diaphragmatic hernia.

PMID- 15437575
TI  - Lipoid pneumonia resulting from a dermoid cyst; case report.

PMID- 15437576
TI  - Acute putrid abscess of the lung. VI. The late results of surgical treatment.

PMID- 15437577
TI  - Transthoracis, thoracoabdominal portacaval anastomosis.

PMID- 15437578
TI  - Disturbances in acid-base balance during ether anesthesia; with special reference
      to the changes occurring during thoracic surgery.

PMID- 15437579
TI  - Continuous spinal anesthesia for thoracoplasty; second report.

PMID- 15437580
TI  - Acanthosis nigricans associated with cancer of the lung; report of a case.

PMID- 15437581
TI  - A report of a case of localized bronchopulmonary aspergillosis successfully
      treated by surgery.

PMID- 15437582
TI  - Neurofibrosarcoma of the anterior mediastinum; surgical removal.

PMID- 15437583
TI  - Cavernous hemangioma of the mediastinum; case report.

PMID- 15437584
TI  - Some aspects of cavity behavior in pulmonary tuberculosis.

PMID- 15437585
TI  - Not by medicine alone.

PMID- 15437586
TI  - Focal pyelonephritis: a cause of severe hematuria.

PMID- 15437587
TI  - Congenital unilateral ectopic kidney: a report of two cases.

PMID- 15437588
TI  - Ureteral implantation: experiments on the surgical principles involved in an open
      submucosal method of uretero-intestinal anastomosis.

PMID- 15437589
TI  - Diagnosis of bladder tumor.

PMID- 15437590
TI  - Treatment of infiltrating carcinoma of bladder by "retrograde method of
      interstitial radiation".

PMID- 15437591
TI  - Diagnostic value of lacunar cystography.

PMID- 15437592
TI  - Adenocarcinoma of urachus involving bladder and abdominal wall.

PMID- 15437593
TI  - Mucinous adenocarcinoma arising in urachal cyst and involving bladder.

PMID- 15437594
TI  - Leiomyoma of the prostate: report of case.

PMID- 15437595
TI  - Polyorchidism: case report.

PMID- 15437596
TI  - Feminizing testis tumors.

PMID- 15437597
TI  - Massive hematocele threatening life by exsanguination.

PMID- 15437598
TI  - Concomitant medical conditions in urologic surgery.

PMID- 15437599
TI  - A simple rotatable electrotome.

PMID- 15437600
TI  - Cutaneous bridges for skin ureterostomy; retention catheters.

PMID- 15437601
TI  - Eight point agreement of 1948.

PMID- 15437602
TI  - Effectiveness of penicillin in preventing congenital syphilis when administered
      prior to pregnancy.

PMID- 15437605
TI  - Measurement of trend of syphilis in Mississippi.

PMID- 15437606
TI  - The Ohio National Guard blood-testing program.

PMID- 15437607
TI  - Treatment of early syphilis with three injections of penicillin and with one
      injection of penicillin.

PMID- 15437608
TI  - Research on intracutaneous test for tuberculosis. I. Intracutaneous test by lung
      tissue extract of caseous pneumonia rabbit.

PMID- 15437609
TI  - Study on the influence of weather on pulmonary tuberculosis. II. Influence of
      front on adrenalin sensibility.

PMID- 15437610
TI  - Change in the result of tuberculin test and the error made by the indirect x-ray
      examination at some factory.

PMID- 15437611
TI  - Experimental study on change in kidney caused by tubercle toxin.

PMID- 15437612
TI  - Study on BCG ferments (on urease and catalase).

PMID- 15437613
TI  - Urine beri-beri reaction and indophenol intracutaneous reaction of pulmonary
      tuberculous patients.

PMID- 15437614
TI  - Tuberculous meningitis and miliary pulmonary tuberculosis in children treated
      with streptomycin.

PMID- 15437615
TI  - [Clinical characteristics of functional modifications in the peripheral nervous
      system in inflammatory processes].

PMID- 15437616
TI  - [Treatment of wounds with Shostakovskii's synthetic balsam (vinilin)].

PMID- 15437617
TI  - [Results in treatment of cancer of the breast by medication of the genital organs
      and the pituitary gland. I. Effect of ovarian castration on the clinical course
      of generalized forms of cancer of the breast].

PMID- 15437618
TI  - [Effect of surgery of abdominal organs in pulmonary tuberculosis].

PMID- 15437619
TI  - [Surgical technic for peptic ulcer].

PMID- 15437620
TI  - [Retrograde catheterization of the esophagus in the presence of a gastric fistula
      as a method facilitating diagnosis of injuries and dilatation of the esophagus].

PMID- 15437621
TI  - [Ectopy of the ureters].

PMID- 15437622
TI  - [History of preliminary treatment of wounds and application of permanent
      sutures].

PMID- 15437623
TI  - [Remote results in Recklinghausen's disease following excision of a tumor of the
      parathyroid gland].

PMID- 15437624
TI  - [Phagedenic ulcer].

PMID- 15437625
TI  - [Two cases of diabetes insipidus following head injuries].

PMID- 15437626
TI  - [Two cases of parapleural surgical approach to the subdiaphragm space by the
      Novikov-Sozon-Iaroshevich method].

PMID- 15437627
TI  - [Cyst of the common bile duct].

PMID- 15437628
TI  - [Case of neuritis of the ulnar nerve as a complication of penicillin therapy].

PMID- 15437629
TI  - [Tissue therapy in strictures of the urethra].

PMID- 15437630
TI  - [Case of extravesical orifice of the ureter].

PMID- 15437631
TI  - [Preparation for base anesthesia].

PMID- 15437632
TI  - [NoAbul'fat Rzakhan Ogly Talyshinskii].

PMID- 15437633
TI  - [Use of roasted whole-grain rye meal in infant nutrition].

PMID- 15437634
TI  - [Injuries caused by intramuscular injection of sulfonamides].

PMID- 15437635
TI  - [Peroral streptomycin therapy of alimentary intoxication].

PMID- 15437636
TI  - [Initial fever cramps and the weather].

PMID- 15437637
TI  - [Diagnosis of Gaucher's disease].

PMID- 15437638
TI  - [Penicillin therapy of a cerebral abscess in an infant].

PMID- 15437639
TI  - [Tuberculosis of the roof of the skull].

PMID- 15437640
TI  - [Wolhynia fever following blood transfusions in an infancy].

PMID- 15437641
TI  - [3 cases of polyradiculitis].

PMID- 15437642
TI  - [Occurrence of spastic pyloristenosis in one of enzygotic twins].

PMID- 15437643
TI  - [Seasonal frequency and dangers of whooping cough].

PMID- 15437644
TI  - [External concentric atrophy of the bones in Erb's progressive muscular
      dystrophy].

PMID- 15437645
TI  - [Effects of storage capacity of the reticuloendothelial system of the liver; data
      on the correlation between the reticuloendothelial and nervous systems].

PMID- 15437646
TI  - [Method of determination of the storage function of the reticuloendothelial
      cells].

PMID- 15437647
TI  - [Endocrine changes in acute experimental tannic acid intoxication with special
      reference to the adrenal cortex].

PMID- 15437648
TI  - [Effect of acetylcholine and cholinesterase on neuromuscular and ganglionic
      synapses].

PMID- 15437649
TI  - [Experimental cystic pancreas degeneration].

PMID- 15437650
TI  - [Adenosine triphosphate, the functional group of actin].

PMID- 15437651
TI  - [Importance of interstitial space and the lymphatic system in ascending
      pyelonephritis].

PMID- 15437652
TI  - [Investigation of pathologic effect of industrial tar].

PMID- 15437653
TI  - [Statistical data in clinical investigations].

PMID- 15437654
TI  - [Remote after effects following surgery of peptic ulcer].

PMID- 15437655
TI  - [Clinical aspect and treatment of hypernephroma].

PMID- 15437656
TI  - [Expert opinion in determination of working ability in cardiovascular diseases].

PMID- 15437657
TI  - [Remote results in the treatment of multiple sclerosis and acute disseminated
      encephalomyelitis with specific vaccine].

PMID- 15437658
TI  - [Remote results following surgery of the stomach for peptic ulcer and working
      ability of the patient].

PMID- 15437660
TI  - [Functional modifications of kidneys in chronic circulatory insufficiency].

PMID- 15437659
TI  - [Symptomatology and diagnosis of thrombosis of renal arteries].

PMID- 15437661
TI  - [Modification of the kidneys in circulatory insufficiencies].

PMID- 15437662
TI  - [Diagnosis of renal stasis and its role in the clinical aspect of circulatory
      insufficiency].

PMID- 15437663
TI  - [Modifications of renal function in hypertonic disease].

PMID- 15437664
TI  - [Reaction of muscular arteries to nitroglycerine in acute and chronic nephritis].

PMID- 15437665
TI  - [Treatment of acute and chronic hepatitis with fresh extracts of the pancreas].

PMID- 15437666
TI  - [Suppurative processes in lungs treated with penicillin].

PMID- 15437667
TI  - [Treatment of bronchial asthma with aeroions].

PMID- 15437668
TI  - [Case of isolated atypic lymphogranulomatosis of the small intestine].

PMID- 15437669
TI  - [Hemopoiesis in application of massive doses of penicillin].

PMID- 15437670
TI  - [Hemodynamic and vegetative shifts in peptic ulcer].

PMID- 15437671
TI  - [Case of acute thrombopenic purpura with extensive cerebral hemorrhage].

PMID- 15437672
TI  - [Advances of contemporary Russian scientists in the field of vitaminology].

PMID- 15437673
TI  - [Gastric and pancreatic secretions in acute parencymatous hepatitis and
      cholecystitis].

PMID- 15437674
TI  - [Variability of the symptom of the niche in roentgenologic studies in cases of
      peptic ulcer].

PMID- 15437675
TI  - [Cardiovascular system in peptic ulcer].

PMID- 15437676
TI  - [Balneotherapy in subacute infectious arthritis].

PMID- 15437677
TI  - [Effect of treatment of hypertonic diseases with intravenous injections of
      magnesium sulfate].

PMID- 15437678
TI  - [The role and purposes of the medical schools].

PMID- 15437679
TI  - [Surgery of lungs].

PMID- 15437680
TI  - [Sergei Sergeevich Lakovlev].

PMID- 15437681
TI  - [Functional pathology in high blood pressure].

PMID- 15437682
TI  - [Combination chemical and roentgenographic therapy in certain malignant tumors].

PMID- 15437683
TI  - [Chronic, non-specific pneumonia and cancer of the bronchi].

PMID- 15437684
TI  - [Functional roentgen ray diagnosis of chronic pulmonary emphysema].

PMID- 15437685
TI  - [Diagnosis of primary cancer of the lungs].

PMID- 15437686
TI  - [Medical investigation of respiration in athletics].

PMID- 15437687
TI  - [Certain forms of sprue].

PMID- 15437688
TI  - [Comments on the article of Prof. A. M. Sigal "Clinical forms of endocarditis and
      their classification"].

PMID- 15437689
TI  - [Classification of endocarditis].

PMID- 15437690
TI  - [Rheumatic and non-rheumatic endocarditis].

PMID- 15437691
TI  - [Significance of barrel-fingers in the prognosis of suppurative diseases of the
      lungs].

PMID- 15437692
TI  - [Clinical significance of the physiologic and pathologic mobility of eye-pupils].

PMID- 15437693
TI  - [Case of successful treatment of acute bronchial asthma with sodium salicylate].

PMID- 15437694
TI  - [Effect of radon baths in Piatigorsk on the modification in the rate of
      hemorrhage and capillaroscopic picture in normal subjects and in patients with
      certain groups of heart diseases].

PMID- 15437695
TI  - [Blood coagulation in the traumatic shock].

PMID- 15437696
TI  - [Nonspecific forms of European recurrent typhus].

PMID- 15437697
TI  - [Treatment of rat bite with penicillin].

PMID- 15437698
TI  - [Excretion of chlorides in tuberculous pneumonia].

PMID- 15437699
TI  - [Function of kidneys in tuberculous pneumonia].

PMID- 15437700
TI  - [Respiratory insufficiencies in certain diseases and injuries, in combination
      with disturbances of the function of the respiratory tract and blood
      circulation].

PMID- 15437701
TI  - [I.P. Pavlov's theories in clinical medicine].

PMID- 15437702
TI  - [Clinical physiology of the pancreas].

PMID- 15437703
TI  - [Progress in treatment of thyrotoxicosis].

PMID- 15437704
TI  - [Therapeutic use of new medicinal preparations].

PMID- 15437705
TI  - [Treatment of dysentery with colloido-dispersed preparation of silver salt of
      sulfathiozole].

PMID- 15437706
TI  - [Clinical aspect of toxic alimentary infections].

PMID- 15437707
TI  - [Clinical manifestations in early stages of ascaridiasis].

PMID- 15437708
TI  - [Clinical manifestations of adipose dystrophy of liver].

PMID- 15437709
TI  - [Fascioliasis of the liver].

PMID- 15437710
TI  - [Recurrence in protracted malaria].

PMID- 15437711
TI  - [Cerebrospinal fluid in malaria comatosa].

PMID- 15437712
TI  - [Clinical aspect of infectious hemorrhagic fever].

PMID- 15437713
TI  - [Surgery of patent ductus arteriosus].

PMID- 15437714
TI  - [Determination of streptomycin concentration by acid-resistant bacteria].

PMID- 15437715
TI  - [Chemical determination of mitogenetic radiation].

PMID- 15437716
TI  - [Diagnosis of cardiac thrombosis during life].

PMID- 15437717
TI  - [Total atrioventricular block following blind gunshot injury of the heart].

PMID- 15437718
TI  - [Resection of embolus of the aortic bifurcation].

PMID- 15437719
TI  - [Diphtheria therapy].

PMID- 15437720
TI  - [Oscillography in diseases with pair syndrome in the region of the heart].

PMID- 15437721
TI  - [Therapeutic use of citral in hypertension].

PMID- 15437722
TI  - [Electrocardiogram in hypertension of ambulatory patients].

PMID- 15437723
TI  - [Modification of ascorbic acid metabolism in blood transfusion].

PMID- 15437724
TI  - [Intravenous method of insulin shock therapy].

PMID- 15437725
TI  - [Scientific, pedagogic and public work of V. D. Shervinskii].

PMID- 15437726
TI  - [Nodular prurigo].

PMID- 15437727
TI  - [Clinical observations on the efficacy of ferronicum].

PMID- 15437728
TI  - [Submucous lipoma of the colon].

PMID- 15437729
TI  - [Results of surgical therapy of uterine cancer].

PMID- 15437730
TI  - [Isolated fracture of the first rib and its mechanical etiology].

PMID- 15437731
TI  - [Treatment of open wounds of the knee].

PMID- 15437732
TI  - [Cytostatic therapy].

PMID- 15437733
TI  - [High blood pressure and diabetes].

PMID- 15437734
TI  - [Retrogression of diabetic cataract in advanced age].

PMID- 15437735
TI  - [Orbital thrombophlebitis and its treatment].

PMID- 15437736
TI  - [Retrobulbar angioendothelioma with pulsating exophthalmos].

PMID- 15437737
TI  - [Plastic surgery of a defect of the orbital roof for correction of vertical
      strabismus with diplopia].

PMID- 15437738
TI  - [Priscol in treatment of diseases of the retina and optic nerve].

PMID- 15437739
TI  - [Medication of the anterior segment of the eye with adrianol eye drops].

PMID- 15437740
TI  - [Indications and methods in privine medication of the eye].

PMID- 15437741
TI  - [Treatment of allergic diseases of the eye with antistin, a new antihistamine].

PMID- 15437742
TI  - [Results of privine and antistin-privine therapy of allergic conjunctivitis].

PMID- 15437743
TI  - [The hemato-aqueous barrier and cysteine].

PMID- 15437744
TI  - [Temporary suture in acute entropium].

PMID- 15437745
TI  - [Use of Dr. Heisler's Kaffeekohle (Carbo Konigsfeld) in ophthalmology].

PMID- 15437746
TI  - [On the date of earliest knowledge of cataract extraction in ancient Greece].

PMID- 15437747
TI  - [Unusual modifications of the retina in Laurence-Biedl syndrome].

PMID- 15437748
TI  - [Constitution and detachment of the retina].

PMID- 15437749
TI  - [Surgical therapy of myopia].

PMID- 15437750
TI  - [Ultrasonic therapy of the eye].

PMID- 15437751
TI  - [Effect of ultrasonic waves upon vitreous and lens].

PMID- 15437752
TI  - [Effect of ultrasonic waves upon the anterior segment of the eye in the living
      rabbit].

PMID- 15437753
TI  - [Two new types of contact plexiglass lens].

PMID- 15437754
TI  - [Use of artificial resin in the manufacture of ocular prostheses and orbital
      implants].

PMID- 15437755
TI  - [Plastic enucleation and polyviol implant].

PMID- 15437756
TI  - [Distortion of the pupil following surgery of congenital gray cataract].

PMID- 15437757
TI  - [Ocular symptoms in herpetic encephalitis].

PMID- 15437758
TI  - [Night blindness in Russian repatriates].

PMID- 15437759
TI  - [Observations on increased ocular tension due to follicular hormone].

PMID- 15437760
TI  - [Electrocoagulation with the oxytherm].

PMID- 15437761
TI  - [Advisability of beginners' attempting intracapsular extraction].

PMID- 15437762
TI  - [Conjunctivitis due to corn cockle seeds].

PMID- 15437763
TI  - [Blood coagulation and coagulation factors].

PMID- 15437764
TI  - [Virus infection in pneumonia].

PMID- 15437765
TI  - [Comparative study of the effect of TB I, a thiosemicarbazone derivative, and of
      the adrenocortical and hypophyseal hormones upon hyperergy and plasma colloids,
      and its significance in the problem of rheumatism].

PMID- 15437766
TI  - [Role of sodium chloride in the excretion of urine].

PMID- 15437767
TI  - [Problem of the pulmonary musculature].

PMID- 15437768
TI  - [Hydrogen ion concentration and capillary permeability in cardiac
      decompensation].

PMID- 15437769
TI  - [Dangers of salvarsan therapy in pregnancy].

PMID- 15437770
TI  - [Morphology and classification of the pathogen of Q fever].

PMID- 15437771
TI  - [Gross inaccuracies of mixing pipets used in erythrocyte and leukocyte count].

PMID- 15437772
TI  - [Effect of cobalt on hemopoiesis].

PMID- 15437773
TI  - [Emission spectrographic studies of serum cobalt].

PMID- 15437774
TI  - [Food dyes and cancer; experiments with 2-4-dioxyazobenzol-2'-4'-disulfonate of
      sodium (chrysoin)].

PMID- 15437775
TI  - [Hypothalamo-hypophyseal regulation of water metabolism].

PMID- 15437776
TI  - [Use of dehydrated ergot alkaloids (CCK 179, hydergin) in the treatment of
      disorders of peripheral circulation and in other sympathicotonic disorders; an
      analytic experiment].

PMID- 15437777
TI  - [Effect of trinitrates upon human circulation].

PMID- 15437778
TI  - [Effect of cocaine in inflammation due to mustard oil and croton oil].

PMID- 15437780
TI  - [Fractional determination of serum protein].

PMID- 15437779
TI  - [The effect of nicotinamide upon glycogenesis and postmortal glycogenolysis].

PMID- 15437781
TI  - [Occurrence of blood group factors in pathological modifications of the
      cerebrospinal fluid].

PMID- 15437782
TI  - [Combination of dibromosalicil with sulfonamides].

PMID- 15437783
TI  - [Investigation of tryptophane metabolism in infants and children].

PMID- 15437784
TI  - [Activation of the bacteriostatic effect of penicillin with traces of metal].

PMID- 15437785
TI  - [Structural modifications of the transverse striation of collagenous fibers].

PMID- 15437786
TI  - [A new method of creatinine determination].

PMID- 15437787
TI  - [Effect of polamidon (Hochst 10820) in increasing pulmonary ventilation following
      administration of carbon dioxide].

PMID- 15437788
TI  - [Problem of aminophenol intoxication in PAS therapy].

PMID- 15437789
TI  - [Intrapulmonary oxidation].

PMID- 15437790
TI  - [Peculiar hemorrhagic diathesis: anticoagulant hemophilia].

PMID- 15437791
TI  - [Mode of action of quicksilver in mercuric chloride poisoning].

PMID- 15437792
TI  - [Animal experimentation of the relation of leucocyte regulation to Wilder's law
      of initial value].

PMID- 15437793
TI  - [Vaccine therapy of typhoid and the Sanarelli-Shwartzman phenomenon].

PMID- 15437794
TI  - [Problem of sciatica and intervertebral disk hernia].

PMID- 15437795
TI  - [Modification of the Weltman coagulation column to increase its sensitivity as a
      liver function test].

PMID- 15437796
TI  - [Quantitative determination of p-oxyphenylpyruvic acid in urine].

PMID- 15437797
TI  - [Experiences with the collodion-precipitin reaction for the detection of auto
      antibodies].

PMID- 15437798
TI  - [Experiments with arterenol in man].

PMID- 15437799
TI  - [Effect of protoporphyrin on the sugar, calcium and potassium level of the
      blood].

PMID- 15437800
TI  - [Giant leukocytes].

PMID- 15437801
TI  - [Heredity of essential hypochromic anemia].

PMID- 15437802
TI  - [Observations on the change, produced by aging, in double refractivity and
      trypsin resistance of the collagenous fibers of scar tissue].

PMID- 15437803
TI  - [Experiments in the transmission of infectious mononucleosis in humans].

PMID- 15437804
TI  - [Studies of so-called residual reduction in the determination of blood-sugar].

PMID- 15437805
TI  - [Demonstration and significance of disorders in regulation of the conjunctival
      capillaries].

PMID- 15437806
TI  - [Differences in tissue respiration of various sections of rat heart].

PMID- 15437807
TI  - [Progress in diagnosis of syphilis with cardiolipin, with personal observations
      on quantitative serum titration].

PMID- 15437808
TI  - [Concentration of the tubercle bacillus by filtration of liquefied sputum].

PMID- 15437809
TI  - [Resistance to TB I].

PMID- 15437810
TI  - [Studies on the Costa reaction].

PMID- 15437811
TI  - [Psychopathology of the tuberculous].

PMID- 15437812
TI  - [Dose and effect].

PMID- 15437813
TI  - [Second carbohydrate metabolism hormone of the pancreas (glucagon) and its origin
      in the alpha cells].

PMID- 15437814
TI  - [Toxic effects of nitrogen mustard therapy].

PMID- 15437815
TI  - [Stilbamidine therapy of generalized plasmocytoma].

PMID- 15437816
TI  - [Comparative studies on the diagnostic value of the Costa reaction].

PMID- 15437817
TI  - [Diagnostic value of the atypical result of Feulgen's nuclear reaction].

PMID- 15437818
TI  - [Recurrent tonsillitis].

PMID- 15437819
TI  - [Acid-base equilibrium of the blood in chronic malnutrition].

PMID- 15437820
TI  - [Fractional sugar level of the cerebrospinal fluid].

PMID- 15437821
TI  - [Sikorski's modification of the Chediak test].

PMID- 15437822
TI  - [Disorders of cell- and tissue metabolism as internal factors in carcinogenesis].

PMID- 15437823
TI  - [Inhibitory effect of peteosthor and its components upon the growth of human
      tubercle bacilli in vitro].

PMID- 15437824
TI  - [Extent of error in blood counting methods].

PMID- 15437825
TI  - [Effect of general and local anesthesia upon the permeability and membrane
      tension of the sartorius muscle in the frog].

PMID- 15437826
TI  - [A new psittacosis epidemic and effective therapy].

PMID- 15437827
TI  - [Antiphlogistic effect of desoxycorticosterone acetate].

PMID- 15437828
TI  - [Etiology of sympathetic ophthalmia].

PMID- 15437829
TI  - [Bacteriologically confirmed cases of necrotizing enteritis in Hamburg and
      Dithmarschen during the period from March 1948 to March 1949].

PMID- 15437830
TI  - [Effect of invert soaps upon mycotic and coccic infections of the skin].

PMID- 15437831
TI  - [Pathogenesis of dermatomyositis].

PMID- 15437832
TI  - [Disorders of protein and lipoid metabolism in hyalinosis of the skin and
      mucosa].

PMID- 15437833
TI  - [Effect of TB I].

PMID- 15437834
TI  - [Results of hemoglobin and serum protein determinations during mass surveys in
      Hesse].

PMID- 15437835
TI  - [Determination of protein in the cerebrospinal fluid].

PMID- 15437836
TI  - [Experimental research in morphology of the diencephalohypophysial system in
      relation to water metabolism].

PMID- 15437837
TI  - [Investigations of the value of blood sedimentation rate in differential
      diagnosis].

PMID- 15437838
TI  - [Effect of hypophyseal transplant upon the regulation of carbohydrate
      metabolism].

PMID- 15437839
TI  - [Secretion of adrenocortical hormone in rheumatic polyarthritis].

PMID- 15437840
TI  - [Attempt at a classification of the Bacterium bifidum].

PMID- 15437841
TI  - [Mechanism of local anesthesia].

PMID- 15437842
TI  - [Resorption of carotene and carotene-vitamin A values of the blood in
      malnutrition; technic in determination of vitamin A and carotene].

PMID- 15437843
TI  - [Copper-protein combination in the blood plasma].

PMID- 15437844
TI  - [Triphenyl-tetrazolium chloride as an indicator of malignant tumors].

PMID- 15437845
TI  - [Influence of the ovarian cycle upon the extent of reactive erythema following
      administration of acetylcholine and prostigmine in combination].

PMID- 15437846
TI  - [A new method of evaluating the coagulation properties of the blood].

PMID- 15437847
TI  - [Effect of sulfonamides upon blood coagulation].

PMID- 15437848
TI  - [Case of alimentary macrocytic anemia during pregnancy (alimentary pernicious
      anemia of pregnancy)].

PMID- 15437849
TI  - [Statistical studies of hemoglobin- and serum protein values].

PMID- 15437850
TI  - [Effect of antihistamine on bee sting].

PMID- 15437851
TI  - [Statistical evaluation of clinical results without formulae, logarithm tables
      and slide rules].

PMID- 15437852
TI  - [Pleuropneumonia-like microorganisms in virus pneumonia].

PMID- 15437853
TI  - [Relation between adrenals and testicles in the rat].

PMID- 15437854
TI  - [Stage-photometric determination of hemoglobin by means of cyanhemoglobin].

PMID- 15437855
TI  - [Experiences with the use of the male Rana esculenta in rapid tests for pregnancy
      in fall and winter].

PMID- 15437856
TI  - [The effect of hydrated ergot alkaloids upon the orthostatic electrocardiogram
      and kymogram].

PMID- 15437857
TI  - [Inhibitory effect of cysteine upon the hemolytic action of coli endotoxin].

PMID- 15437858
TI  - [Franz Volhard].

PMID- 15437859
TI  - [Familial idiopathic tetany with polyglandular insufficiency].

PMID- 15437860
TI  - [Simmond's cachexia and diabetes].

PMID- 15437861
TI  - [Antagonism of thyroxin and benzoic acid].

PMID- 15437862
TI  - [Identification of a leukolytic substance in the blood in panmyelophthisis].

PMID- 15437863
TI  - [Investigation of the tyrosine content of the blood following intravenous load].

PMID- 15437864
TI  - [Protein and mucus content of the bile in normal state, in parenchymal disease of
      the liver, and in diseases of the bile ducts].

PMID- 15437865
TI  - [Experiments in evaluating the conductivity of the human brain in a high
      frequency field].

PMID- 15437866
TI  - [Clinical investigations of Rothschuh's principle of multiple differential
      analysis in electrocardiography].

PMID- 15437867
TI  - [Electroshock and fibrinolysis].

PMID- 15437868
TI  - [The hydrochloric acid-collargol reaction in examination of the cerebrospinal
      fluid].

PMID- 15437869
TI  - [Manifestations of intoxication following administration of novocain subsequent
      to injection of Evan's blue].

PMID- 15437870
TI  - [Determination of resistance in chemotherapy].

PMID- 15437871
TI  - [Effect of lipotropic substances upon blood and liver lipoids in experimental
      fatty liver and in liver cirrhosis in man].

PMID- 15437872
TI  - [Improvements in titrimetric determination of blood potassium with Rappaport's
      method].

PMID- 15437873
TI  - [Neurotropic mechanism of penicillin poisoning].

PMID- 15437874
TI  - [Causes of retardation and amplification of the first heart tone in mitral
      stenosis and absolute arrhythmia].

PMID- 15437875
TI  - [Aureomycin therapy of pulmonary abscess].

PMID- 15437876
TI  - [Prognostic significance of the cerebrospinal fluid in tuberculous meningitis
      treated with streptomycin].

PMID- 15437877
TI  - [Complementary datum of interest in the present bacilloscopy of tuberculosis
      products].

PMID- 15437878
TI  - [Evaluation of blood proteins in relation to the normal mean].

PMID- 15437879
TI  - [Hematocrit value; its importance; its usefulness in view of the possibility of
      substituting in current practice the globular value for the volume index of
      analogous clinical significance].

PMID- 15437880
TI  - The three types of "natural" diuresis.

PMID- 15437881
TI  - The effect of splanchnicectomy on renal function.

PMID- 15437882
TI  - Aureomycin and amoebic dysentery.

PMID- 15437883
TI  - Clinical trial of xylocaine in local anaesthesia.

PMID- 15437884
TI  - Transmission of staphylococcal antitoxin (anti-haemolysin) from mother to child.

PMID- 15437885
TI  - Rapid determination of blood-sugar; a simple method.

PMID- 15437886
TI  - The cost of the hospital service in a teaching hospital.

PMID- 15437887
TI  - The Alexander libel action.

PMID- 15437888
TI  - HEIGHTS and weights of London school children.

PMID- 15437889
TI  - Investigation of thyroid function and disease with radioactive iodine.

PMID- 15437890
TI  - Synergism and antagonism as displayed by certain antibacterial substances.

PMID- 15437891
TI  - Ephedrine in a screening test for cortisone substitutes.

PMID- 15437892
TI  - Haemophilus influenzae meningitis; report of 5 cases.

PMID- 15437893
TI  - Sudden death of young athlete from rupture of ascending aorta.

PMID- 15437894
TI  - Progressive lipodystrophy; report of 2 cases.

PMID- 15437895
TI  - Disposable ileocolostomy bags.

PMID- 15437896
TI  - Significance of the discovery of the effects of cortisone on rheumatoid
      arthritis.

PMID- 15437897
TI  - Investigation of thyroid function and disease with radioactive iodine.

PMID- 15437898
TI  - Domiciliary treatment of pulmonary tuberculosis with sodium para-aminosalicylate.

PMID- 15437899
TI  - A case of Brill's disease in London.

PMID- 15437900
TI  - Note on a case of Brill's disease in London.

PMID- 15437901
TI  - Clinical pathology under the National Health Service.

PMID- 15437902
TI  - CENTRAL Health Services Council.

PMID- 15437903
TI  - Nursing and tuberculosis in a general hospital.

PMID- 15437904
TI  - Pregnenolone in the treatment of rheumatoid arthritis.

PMID- 15437905
TI  - Puerperal uraemia due to acute upper-nephron nephrosis; report of three cases.

PMID- 15437906
TI  - Enuresis in adults and abnormality of sleep.

PMID- 15437907
TI  - Excretion of potassium after partial gastrectomy.

PMID- 15437908
TI  - The two conceptions of science.

PMID- 15437909
TI  - Neurosurgical treatment of persistent pain.

PMID- 15437910
TI  - Purpura in pregnancy with special reference to idiopathic thrombocytopenic
      purpura.

PMID- 15437911
TI  - Salicylates in acute osteomyelitis.

PMID- 15437912
TI  - Dimercaprol in acute lead poisoning.

PMID- 15437913
TI  - Fatal Salmonella infection simulating enteric fever.

PMID- 15437914
TI  - A modified Mayo vein stripper.

PMID- 15437915
TI  - Neonatal diarrhoea and vomiting; outbreaks in the same maternity unit.

PMID- 15437916
TI  - Transvesical suprapubic prostatectomy with closure of the bladder; review of 40
      cases.

PMID- 15437917
TI  - Acquired idiosyncrasy to sodium p-aminosalicylate.

PMID- 15437918
TI  - Meigs's syndrome.

PMID- 15437919
TI  - Meningitis leptospirosa.

PMID- 15437920
TI  - Relief of postoperative pain and intestinal motility.

PMID- 15437921
TI  - Response to adrenocorticotropic hormone and cortisone in persons with carcinoma,
      leukaemia, and lymphosarcoma.

PMID- 15437922
TI  - Lung carcinoma in Iceland.

PMID- 15437923
TI  - Protection of the skin from sunburn; comparison of the absorption spectra of
      screening agents and their efficacy in eczema solare.

PMID- 15437924
TI  - Decamethonium iodide in muscular hypertonus.

PMID- 15437925
TI  - Rupture of the pregnant uterus by external violence.

PMID- 15437926
TI  - Simple "booster" for obstetric gas-air apparatus.

PMID- 15437927
TI  - Q fever in North Wales.

PMID- 15437928
TI  - POLIOMYELITIS.

PMID- 15437929
TI  - INFECTIOUS diseases in England and Wales.

PMID- 15437930
TI  - Effects of intrathecal tuberculin and streptomycin in tuberculous meningitis; an
      interim report.

PMID- 15437931
TI  - Thiosemicarbazone in the treatment of leprosy.

PMID- 15437932
TI  - Streptomycin in subacute bacterial endocarditis; report of 3 cases.

PMID- 15437933
TI  - Puerperal gangrene.

PMID- 15437934
TI  - Exchange transfusion apparatus.

PMID- 15437935
TI  - Functional costing for hospitals on a "standard" basis.

PMID- 15437936
TI  - Discussion methods in preclinical teaching.

PMID- 15437937
TI  - Education for general practice; the psychosocial factors.

PMID- 15437938
TI  - Origins and outcomes of the patient's stay in hospital; report on a project of
      teaching social medicine.

PMID- 15437939
TI  - Teaching of social medicine in the University of Sheffield.

PMID- 15437940
TI  - "An unconscionable time a-dying"; some outmoded practices still current.

PMID- 15437941
TI  - WAYS into general practice.

PMID- 15437942
TI  - The examination paper.

PMID- 15437943
TI  - LANCET Students' Guide 1950-51.

PMID- 15437944
TI  - DEFENCE services.

PMID- 15437945
TI  - HEALTH services at home.

PMID- 15437946
TI  - "Medical sympathectomy" in hypertension; a clinical study of methonium compounds.

PMID- 15437947
TI  - Pentamethonium in hypertension.

PMID- 15437948
TI  - [Protection and assistance of illegitimate children].

PMID- 15437949
TI  - [Protection of the illegitimate child in family laws].

PMID- 15437950
TI  - [Assistance to illegitimate children in the laws proposed by Bianchi and by
      Gennai-Tonnietti and Migliori].

PMID- 15437951
TI  - [Protection and assistance of illegitimate children; discussion].

PMID- 15437952
TI  - [Pathogenesis and therapy of rheumatic diseases].

PMID- 15437953
TI  - [Two cases of Oppenheim's myatonia congenita].

PMID- 15437954
TI  - [Importance of orthoptics].

PMID- 15437955
TI  - [Surgery of common bile duct].

PMID- 15437956
TI  - [Three periods in the treatment of pyoderma in children].

PMID- 15437958
TI  - [Treatment of liver diseases].

PMID- 15437957
TI  - [Prague method of treatment of scarlet fever with penicillin (Prochazka-Ra6ska)].

PMID- 15437959
TI  - [Transportation of sick and disinfection in Brno until 1947].

PMID- 15437960
TI  - [Seventieth anniversary of Ji6ra Trapl].

PMID- 15437961
TI  - [From Leeuwenhoek to proton microscope].

PMID- 15437962
TI  - [Isolation of the virus of human meningoencephalitis from a tick].

PMID- 15437963
TI  - [Subdural hematoma diagnosed by arteriography].

PMID- 15437964
TI  - [Narcogen].

PMID- 15437965
TI  - [Suspension cast in treatment of fractures of the humerus].

PMID- 15437966
TI  - [Progress in diagnosis and therapy of diseases of the biliary tract].

PMID- 15437967
TI  - [Stages of development of bacteriophage].

PMID- 15437968
TI  - [Remarks on the surgical treatment of hypertension].

PMID- 15437969
TI  - [Early diagnosis of extensive intracranial tumors].

PMID- 15437970
TI  - [BCG diagnostic test].

PMID- 15437971
TI  - [Two cases of intestinal invagination of Meckel's diverticulum].

PMID- 15437972
TI  - [Honeycomb lungs].

PMID- 15437973
TI  - [Investigation of late results of Filatov's tissue therapy].

PMID- 15437974
TI  - [Contribution to bronchography].

PMID- 15437975
TI  - [Remote results with penicillin therapy, recurrence and use of newer antibiotics
      in the therapy of subacute bacterial endocarditis].

PMID- 15437976
TI  - [Painless labor with nitrous oxide].

PMID- 15437977
TI  - [Conduct of painless labor].

PMID- 15437978
TI  - [Strangulation by accident].

PMID- 15437979
TI  - [Chemotherapy in the treatment of pulmonary tuberculosis (PAS)].

PMID- 15437980
TI  - [New trends in pediatrics].

PMID- 15437981
TI  - [The state of health in the region of Morava-Silezea].

PMID- 15437982
TI  - [Training of medical personnel and social workers in Brno to 1947].

PMID- 15437983
TI  - [Franti6sek Pavlak, 70th anniversary].

PMID- 15437984
TI  - [Early diagnosis of genital carcinoma].

PMID- 15437985
TI  - [Cardiovascular diseases due to cyanosis; stenosis of the pulmonary artery].

PMID- 15437986
TI  - [Certain aspects of contemporary thoracic surgery].

PMID- 15437987
TI  - [Renal function tests by the method of clearance].

PMID- 15437988
TI  - [Congenital malformations of the heart].

PMID- 15437989
TI  - [Not Available].

PMID- 15437990
TI  - [Congenital idiopathic methemoglobinemia].

PMID- 15437991
TI  - [Case of intra-cardial injection; vitum artis].

PMID- 15437992
TI  - [The phenomenon of neurography].

PMID- 15437993
TI  - [Application of heat in so called functional therapy, of fractures of the
      joints].

PMID- 15437995
TI  - [Ascariasis of the fallopian tube].

PMID- 15437994
TI  - [Subcutaneous emphysema sub partu].

PMID- 15437996
TI  - [Studies on amyloidosis].

PMID- 15437997
TI  - [Medicine in Zadar].

PMID- 15437998
TI  - Medico-moral notes.

PMID- 15437999
TI  - Original sin and education.

PMID- 15438000
TI  - Materialism and modern medicine.

PMID- 15438001
TI  - [Tuberculosis mortality in Italy during and after the war].

PMID- 15438002
TI  - [New applications of kymography in the study of tuberculous caverns].

PMID- 15438003
TI  - [Streptomycin and pneumothorax in the treatment of recent ulcerative pulmonary
      processes].

PMID- 15438004
TI  - [Advantages and disadvantages of the various surgical approaches to the costal
      wall in extrapleural pneumothorax].

PMID- 15438006
TI  - [Statistical data relative to the mass x-ray of Agenti di P. S. and CC. and the
      valuation in relation to the environmental factor].

PMID- 15438005
TI  - [PAS in the treatment of pleuropulmonary tuberculosis].

PMID- 15438007
TI  - [Re-education and rehabilitation of tuberculous patients in the sanatorium of
      Garbagnate].

PMID- 15438008
TI  - [In memory of Arcangelo Ilvento: "...and he exalted the humble."].

PMID- 15438009
TI  - [Activity of the provincial anti-tuberculosis syndicates].

PMID- 15438010
TI  - [Antonio Bareggi].

PMID- 15438011
TI  - [Indications for surgical treatment of chronic spontaneous non-tuberculous
      pneumothorax].

PMID- 15438012
TI  - [Thiermann's approach for Richer's operation; resection of the hypogastric and
      erector nerves by sacral approach].

PMID- 15438013
TI  - [Surgery for jaundice due to hepatitis; periarterial sympathectomy of the hepatic
      artery].

PMID- 15438014
TI  - [Implantation of the common bile duct and pancreas in the jejunum in exeresis for
      cancer of the head of the pancreas].

PMID- 15438015
TI  - [Sub-phrenic abscesses].

PMID- 15438016
TI  - [Lebrun's prostatectomy].

PMID- 15438017
TI  - [Late results of malignant tumors of the bones of the extremities; osteosarcomas
      and Ewing tumors].

PMID- 15438018
TI  - [Present state of anesthesia in England].

PMID- 15438019
TI  - [Respective uses of continuous spinal anesthesia and general anesthesia with
      intubation and controlled respiration].

PMID- 15438020
TI  - [Postoperative pulmonary atelectasis].

PMID- 15438021
TI  - [Postoperative atelectasis of the remaining lobe after lobectomy].

PMID- 15438022
TI  - [Carbuncle of the lower lip; ascending phlebitis; penicillin resistance; cure by
      aureomycin].

PMID- 15438023
TI  - [Thoracic anus of traumatic origin].

PMID- 15438024
TI  - [Limited ossifying osteosarcomas, of slow evolution, improperly called osteomas].

PMID- 15438025
TI  - [Chronic jaundice due to neoplasm of the bifurcation of the cystic and hepatic
      ducts; anastomosis of a branch of the hepatic duct with the stomach].

PMID- 15438026
TI  - [Simultaneous epitheliomas of the uterus and ovary].

PMID- 15438027
TI  - [Hepatocholangio-enterostomy].

PMID- 15438028
TI  - [Aureomycin cure of two cases of staphylococci infection resistant to penicillin
      and streptomycin].

PMID- 15438029
TI  - [Wolffian tumor of the ovary; uterine and vaginal metastases].

PMID- 15438030
TI  - [Painful amputation stump of venous origin].

PMID- 15438031
TI  - [Cancer of the cecum; spontaneous ileocecal fistula].

PMID- 15438032
TI  - [Surgical treatment of mitral stenosis: interauricular anastomosis; experimental
      note].

PMID- 15438033
TI  - [A series of observations on the congenital absence of the fibula].

PMID- 15438034
TI  - [Treatment of congenital absence of the fibula].

PMID- 15438035
TI  - [Two cases of typical osteoid osteoma].

PMID- 15438036
TI  - [Not Available].

PMID- 15438037
TI  - [Circumscribed tumor of the pleura; anatomo-radiologic comparison].

PMID- 15438038
TI  - [Infectious endocarditis partially treated].

PMID- 15438039
TI  - [Infarct of the myocardium with perforation of the interventricular septum; two
      cases].

PMID- 15438040
TI  - [Considerations on the mechanism of pain during the evolution of cancer].

PMID- 15438041
TI  - [First therapeutic results of the use of the orthobiotic serum of the Pasteur
      Institute].

PMID- 15438042
TI  - [Effects of caffeinated ergotamine tartrate in migraine attacks (E. C. 110 or
      cafergon); first results].

PMID- 15438043
TI  - [Hemorrhagic syndrome with momentary disappearance of prothrombin during a
      complicated tuberculosis primary complex treated by streptomycin and
      paraaminosalicylic acid; probably due to PAS].

PMID- 15438044
TI  - [Some remarks of yesterday and today on medicine, therapeutics, doctors, and
      patients].

PMID- 15438045
TI  - [Action of thrombin on the serofibrinous pleurisies of substitution of
      therapeutic pneumothorax].

PMID- 15438046
TI  - [Left hemithoracic atelectasis during the evolution of a mitral endocarditis].

PMID- 15438047
TI  - [Case of hypoferric anemia of pseudo-hypoplastic form].

PMID- 15438048
TI  - [Conjugal tuberculosis superinfection by streptomycin resistant Koch bacillus].

PMID- 15438049
TI  - [Action of phenergan syrup on gastric pains].

PMID- 15438050
TI  - [Comparative study of the velocity of erythrocyte sedimentation observed by the
      methods of Westergreen and of Cordier-Chaix, especially the sedimentation of the
      first quarter hour].

PMID- 15438051
TI  - [Some remarks of yesterday and of today on medicine, therapeutics, doctors and
      patients].

PMID- 15438052
TI  - [Results of electroencephalography in the study of cerebral tumors].

PMID- 15438053
TI  - [Case of Recklinghausen's neurofibromatosis with osseous localizations].

PMID- 15438054
TI  - [Functional exploration of the lung in pulmonary sclerosis].

PMID- 15438055
TI  - [Bouillaud's disease; salicylate acidosis; papillary edema; treatment with solium
      gentisate].

PMID- 15438056
TI  - [Grave rheumatism; pericarditis; pleurisy resistant to sodium salicylate and to
      sodium gentisate; efficacy of antipyrine].

PMID- 15438057
TI  - [Angina due to staphylococcus complicated by acute nephritis].

PMID- 15438058
TI  - [Vaquez disease, symptomatic of a slowly progressing cancer of the prostate with
      osseous metastases; cure of the polycythemia by hormonal treatment of the
      cancer].

PMID- 15438059
TI  - [Difficulties and possibilities in the diagnosis of tuberculous meningitis].

PMID- 15438060
TI  - [Postscarlatinal gangrene].

PMID- 15438061
TI  - [Remarkable case of Werdnig-Hoffman's muscular dystrophy in early infancy].

PMID- 15438062
TI  - [Indications for splenectomy in cases of essential thrombopenie in children].

PMID- 15438063
TI  - Rh ORGANIZATION and research in the Netherlands.

PMID- 15438064
TI  - Introduction.

PMID- 15438065
TI  - The activity of the Netherlands Red Cross in the field of blood transfusion
      service.

PMID- 15438066
TI  - Rh-organization in the Netherlands.

PMID- 15438067
TI  - Serological aspects of the placenta and other organs in the hemolytic diseases of
      the newborn caused by Rhesus antagonism.

PMID- 15438068
TI  - Serological investigations of the anti human globulin serum (serum of Coombs)
      with special reference to the pathogenesis of erythroblastosis foetalis.

PMID- 15438069
TI  - The difference in the genetic relation of Cw to C and c, and Du to D and d.

PMID- 15438070
TI  - On placenta permeability and antibody varieties in Rhesus immunization.

PMID- 15438071
TI  - Erythroblastosis foetalis and prenatal care.

PMID- 15438072
TI  - Some remarks on the microscopic structure of the placenta in erythroblastosis.

PMID- 15438073
TI  - Clinical, haematological and serological symptoms in the newborn child suffering
      from hemolytic disease of the newborn due to Rhesus-antagonism.

PMID- 15438074
TI  - Technique of the exsanguination-transfusion.

PMID- 15438075
TI  - Experiences in the treatment of erythroblastosis fetalis.

PMID- 15438076
TI  - Haematological aspects of the morbus haemolyticus neonatorum.

PMID- 15438077
TI  - [Significance of the Pharmaconomia and the new Pharmacopeia for the physician].

PMID- 15438078
TI  - [Not Available].

PMID- 15438079
TI  - [The sense of loneliness in the normal and abnormal mental life].

PMID- 15438080
TI  - [Choice of antibiotics and chemotherapeutics in infection].

PMID- 15438081
TI  - [Sick children of today].

PMID- 15438082
TI  - [The Housewife's Aid in Copenhagen].

PMID- 15438083
TI  - [The definition of disability according to the Disability Compensation Law].

PMID- 15438084
TI  - [Not Available].

PMID- 15438085
TI  - [Not Available].

PMID- 15438086
TI  - [Problems of employment disability].

PMID- 15438087
TI  - [Not Available].

PMID- 15438088
TI  - [Extract from the 1948 report of the Directors of the Hospital Service].

PMID- 15438089
TI  - [Place of the Tolocsinov-Duhrssen tamponment in the treatment of hemorrhage
      occurring after placental delivery].

PMID- 15438090
TI  - [Recent research on the possible correlation of cystic glandular hyperplasia and
      genital carcinoma].

PMID- 15438091
TI  - [Tumors in the retroperitoneal space].

PMID- 15438092
TI  - [Primary tuberculosis of the Bartholin glands].

PMID- 15438093
TI  - [Three interesting cases of placenta praevia].

PMID- 15438094
TI  - [Effect of intrauterine administration of follicular and luteinic hormones].

PMID- 15438095
TI  - [On the relation between the metabolism of vitamin C and the follicular hormone].

PMID- 15438096
TI  - [Rupture of the follicle].

PMID- 15438097
TI  - [Farris' rat reaction in determination of human ovulation time].

PMID- 15438098
TI  - [Effect of vitamin C and ovulation].

PMID- 15438100
TI  - [Biology of the cervix uteri].

PMID- 15438101
TI  - [Clinical aspect of ovarian hemorrhage].

PMID- 15438102
TI  - [Most recent results of surgery of the esophagus and cardia].

PMID- 15438103
TI  - [Epiphrenic diverticula of the esophagus].

PMID- 15438104
TI  - [Surgical therapy of diaphragmatic hernia].

PMID- 15438105
TI  - [Mediastinal abscess].

PMID- 15438106
TI  - [Intratracheal anesthesia].

PMID- 15438107
TI  - [Research on lobectomy and pulmonectomy in the USSR].

PMID- 15438108
TI  - [Disease of the intervertebral disks; chances for rehabilitation].

PMID- 15438109
TI  - [New automatic ligator in vascular surgery].

PMID- 15438110
TI  - [Simplified retropubic prostatectomy].

PMID- 15438111
TI  - [Two cases of pubic osteitis].

PMID- 15438112
TI  - [Modifications of clearance in vesiculary retention of the urine].

PMID- 15438113
TI  - [Problem of the formation of urinary incrustations and calculi].

PMID- 15438115
TI  - [Pseudohermaphroditism with hyperplasia of the suprarenal cortex].

PMID- 15438114
TI  - [Prognosis of malignant tumors of the bladder according to their histology].

PMID- 15438116
TI  - [Clinical course, diagnosis and treatment of prostatic carcinoma].

PMID- 15438117
TI  - [Closure of large laryngotracheal fistulas].

PMID- 15438118
TI  - [New instrument for treatment of pulmonary abscess].

PMID- 15438119
TI  - [Exposure of the pyramid by way of the cranial base; anatomo-topographic studies
      based upon experience in dissection].

PMID- 15438120
TI  - [Examination of the auditory apparatus following fenestration in otosclerosis;
      role of aerial and osseous conduction in the hearing in otosclerosis].

PMID- 15438121
TI  - [Pathological effect of noise].

PMID- 15438122
TI  - SYMPOSIUM on caesarean section and uterine prolapse.

PMID- 15438123
TI  - Anemia, a sign of disease.

PMID- 15438124
TI  - The future of Western equine encephalitis.

PMID- 15438125
TI  - Report and comments on the Red Cross Blood Bank, March, 1950.

PMID- 15438126
TI  - Hematocrit.

PMID- 15438127
TI  - Red cell indices.

PMID- 15438128
TI  - Tracheotomy in acute laryngotracheitis.

PMID- 15438129
TI  - Umbilical cord anomalies.

PMID- 15438130
TI  - Bilateral cryptorchidism; Torek operation.

PMID- 15438131
TI  - Topical dermatologic therapy.

PMID- 15438132
TI  - Hip joint disease during the first decade and a half.

PMID- 15438133
TI  - The treatment of compound fractures.

PMID- 15438134
TI  - Diseases of the scrotum and contents.

PMID- 15438135
TI  - The anaemias and blood transfusion.

PMID- 15438136
TI  - Clinical pathology; the blood smear.

PMID- 15438137
TI  - Acute obstructive cholecystitis; cholecystectomy.

PMID- 15438138
TI  - Spanish practice.

PMID- 15438139
TI  - Impressions from the First International and Fourth American Congress on
      Obstetrics and Gynecology.

PMID- 15438140
TI  - On the functioning of the Red Cross blood bank during the Manitoba flood of
      spring 1950.

PMID- 15438141
TI  - The other side of the fence.

PMID- 15438142
TI  - Reports and comments on the Red Cross bank. June, 1950.

PMID- 15438143
TI  - Recent research on oils and fats.

PMID- 15438144
TI  - The melanins--a field of study for cosmetic chemists.

PMID- 15438146
TI  - PERFUMERY and essential oils.

PMID- 15438145
TI  - Luminescent materials.

PMID- 15438147
TI  - ECONOMIC poisons.

PMID- 15438148
TI  - DETERGENTS and detergency.

PMID- 15438149
TI  - GLAXO'S Italian factory.

PMID- 15438150
TI  - [Spread of rabies by rats].

PMID- 15438151
TI  - [Nevoid diseases and oligophrenia].

PMID- 15438152
TI  - [Case of left hemihypertrophy].

PMID- 15438153
TI  - [A disease of Moslem infants; edematous disease of weaning; pathogenesis].

PMID- 15438154
TI  - [Statistics of cases treated at the Centre Bergonie during 1949].

PMID- 15438155
TI  - [Treatment of gonorrhea and syphilis].

PMID- 15438156
TI  - [General assembly of the International Union against Venereal Diseases, Rome, 12
      16 September 1949].

PMID- 15438157
TI  - [New chemotherapy of tuberculosis].

PMID- 15438158
TI  - [Distemper in Morocco; clinical observations].

PMID- 15438159
TI  - [Psoriasis].

PMID- 15438160
TI  - [The role of the Directorate of Public Health in the control of drinking water in
      Morocco].

PMID- 15438161
TI  - [Supply of drinking water of the large towns of Morocco in 1932].

PMID- 15438162
TI  - [Is the presence of fluorine in drinking water harmful or beneficial?].

PMID- 15438163
TI  - [Hydrogeology and supply of drinking water of the cities of Morocco].

PMID- 15438164
TI  - [Distribution of saline water in Morocco and its potability].

PMID- 15438165
TI  - [Hygienic interpretation of a chemical analysis of water].

PMID- 15438166
TI  - [Procedures for the purification of water and their possible application in
      Morocco].

PMID- 15438167
TI  - [The usefulness of determining the fecal contamination of water by at least two
      methods].

PMID- 15438168
TI  - [Critical and comparative study of some methods of determining the fecal
      contamination of water].

PMID- 15438169
TI  - [Drinking water at Tangier; good and bad examples].

PMID- 15438171
TI  - [Water supply of Rabat].

PMID- 15438170
TI  - [The Fouarat and water supply of towns of the north Atlantic coast of Morocco,
      from Port-Lyautey to Casablanca].

PMID- 15438172
TI  - [Water supply of Casablanca].

PMID- 15438173
TI  - [Water supply of Fes].

PMID- 15438174
TI  - [Drinking water supply of Marrakech].

PMID- 15438175
TI  - [How the ascending water bed of Oujda was discovered].

PMID- 15438176
TI  - [Utilization of ground water as a source of supply for the rural centers of Oujda
      region].

PMID- 15438177
TI  - [Purification of the water supply of Khouribga].

PMID- 15438178
TI  - [Water supply of two rural centers in the region of Meknes].

PMID- 15438179
TI  - [Is the use of springs for the supply of drinking water of rural centers an
      optimum?].

PMID- 15438180
TI  - [Water supply of the tribe of Ziaida].

PMID- 15438181
TI  - [Piping water to Casablanca from Oum er R'Bia].

PMID- 15438182
TI  - [Rites and customs of water].

PMID- 15438183
TI  - [Lumbo-sacral spina bifida occulta].

PMID- 15438184
TI  - ["Contact hips"].

PMID- 15438185
TI  - [Planes and spaces of the thoracic wall; surgical anatomy].

PMID- 15438186
TI  - [Umbilical hernia of the newborn].

PMID- 15438187
TI  - [Indications for closed circuit anesthesia and intravenous anesthesia].

PMID- 15438188
TI  - [Early secondary resection of the clavicle in a case of osteomyelitis].

PMID- 15438189
TI  - [Cure of an old infected cavity with an injection of placenta mash].

PMID- 15438190
TI  - [Recurrence of intestinal tuberculosis in the anastomosis after ileocecal
      resection].

PMID- 15438192
TI  - [Persistance of the omphalomesenteric canal; intestinal occlusion].

PMID- 15438191
TI  - [Value of the direct measurement of the level of tissue proteins].

PMID- 15438193
TI  - [Therapeutic effect of protein hydrolysates in protein deficiency states].

PMID- 15438194
TI  - [Arthroplasty of the hip with acrylic prosthesis].

PMID- 15438195
TI  - [Case of maxillary sinusitis due to an impacted canine tooth].

PMID- 15438196
TI  - [Missed arterial embolism].

PMID- 15438197
TI  - [Bloody urine found on catheterization after hysterectomy].

PMID- 15438198
TI  - [Impotence due to castration treated by hormone therapy].

PMID- 15438199
TI  - [Congenital arterio-venous fistula of the foot requiring amputation].

PMID- 15438200
TI  - [Foreign body in the thoracic wall discovered radiologically 6 days after an
      accident in a 5-year-old child].

PMID- 15438201
TI  - [Tumor of the maxilla].

PMID- 15438202
TI  - [Phlebography by intra-malleolar route].

PMID- 15438203
TI  - [Autograft treatment of the associated syndrome of a war wound of the sciatic
      nerve].

PMID- 15438204
TI  - [Congenital dislocation of the hip; arthroplasty].

PMID- 15438205
TI  - [Prefrontal leukotomy and topectomy in the treatment of intractable pain; 9
      observations].

PMID- 15438207
TI  - [Acroparesthesia].

PMID- 15438206
TI  - [Early diagnosis of ankylopoietic spondylarthritis].

PMID- 15438208
TI  - [Arthrosis of the knee; symptoms, diagnosis, treatment].

PMID- 15438209
TI  - [Arthrosis].

PMID- 15438210
TI  - [Arthrosis of the foot].

PMID- 15438211
TI  - [Hydrarthrosis in rheumatology].

PMID- 15438212
TI  - [Morbidity and mortality in relation to occupation].

PMID- 15438213
TI  - [Food and health].

PMID- 15438214
TI  - [Food and health].

PMID- 15438215
TI  - [Forms of medical practice through history].

PMID- 15438216
TI  - [Organization of social security in the world].

PMID- 15438217
TI  - [For humane medicine].

PMID- 15438218
TI  - [Medicine of the total man; perspectives and dangers of neo-hippocratism;
      medicine in the service of man].

PMID- 15438219
TI  - [Anomalies of compensation for occupational diseases].

PMID- 15438220
TI  - [The right to health].

PMID- 15438221
TI  - [Articular gout; clinical aspects and treatment].

PMID- 15438222
TI  - [Pains localized in the elbow; epicondylalgia, epitrochlealgia, olecranalgia].

PMID- 15438223
TI  - [Postural disorders and chronic rheumatism].

PMID- 15438224
TI  - [Cortisone and A.C.T.H. in rheumatology].

PMID- 15438225
TI  - [What the practitioner should know about indications for surgery in
      rheumatology].

PMID- 15438226
TI  - [Mineral water therapy of Bouillaud's disease].

PMID- 15438227
TI  - [Steroid compounds and rheumatism].

PMID- 15438228
TI  - [Different questions in articular pathology].

PMID- 15438229
TI  - [Radioactivity in France].

PMID- 15438230
TI  - [Medical aspects of atomic warfare].

PMID- 15438232
TI  - [Surgery in its relations with social evolution].

PMID- 15438231
TI  - [Indications for surgical treatment of lumbar sciatica].

PMID- 15438234
TI  - [The Supervisory Council of the A.P. and freedom of opinion].

PMID- 15438233
TI  - [Mechanism of action of iodine in hyperthyroidism].

PMID- 15438235
TI  - ["France lacks doctors," by J. B. Rozoy; thesis refused by the Faculty of
      Medicine of Paris].

PMID- 15438236
TI  - [Inadmissible reasons adduced; suspension of two industrial physicians by the
      Regional Council for having treated employees of their company].

PMID- 15438237
TI  - [Clinical aspect of Queensland fever].

PMID- 15438238
TI  - [Clinical aspect and treatment of cervical rheumatism].

PMID- 15438239
TI  - [Mandibular movements and their mechanical reproduction].

PMID- 15438240
TI  - [Operative and orthodontic treatment of an impacted canine tooth].

PMID- 15438241
TI  - [Where is pediatrics going?].

PMID- 15438242
TI  - [Auxology or the science of human growth].

PMID- 15438243
TI  - [Present problems of tuberculin tests in the child].

PMID- 15438244
TI  - [Some historical data on the carob bean].

PMID- 15438245
TI  - [Active immunization in series in pediatrics].

PMID- 15438246
TI  - [Relations between immunity and epidemiology in diphtheria].

PMID- 15438247
TI  - [The role of infectious factors in the appearance of congenital malformations].

PMID- 15438248
TI  - [Racial constitution of the Greek child].

PMID- 15438249
TI  - [Treatment of toxicosis of the infant].

PMID- 15438250
TI  - [Pharmacodynamics of antibiotics streptomycin and dihydrostreptomycin].

PMID- 15438251
TI  - [Belgium's effort in the protection of children].

PMID- 15438252
TI  - [Treatment of dysenteriform enterocolitis in the child].

PMID- 15438253
TI  - [Importance of neurosurgery in pediatrics].

PMID- 15438254
TI  - [Radiology of tuberculosis primary complex].

PMID- 15438255
TI  - [Is saving the premature worth while?].

PMID- 15438256
TI  - [New conceptions of the pathogenesis of acrodynia and its treatment].

PMID- 15438257
TI  - [Vaccination by B. C. G..].

PMID- 15438258
TI  - [Pulmonary tuberculosis and pregnancy].

PMID- 15438259
TI  - [Mandibular movements and their mechanical reproduction (articulators)].

PMID- 15438260
TI  - [Round-table on social pediatrics, in relation with the VI International Congress
      of Pediatrics, Geneva, 31 July-5 August 1950].

PMID- 15438261
TI  - [Prophylaxis and care of premature infants].

PMID- 15438262
TI  - [Nutritional state of children of pre-school age in the tropics].

PMID- 15438263
TI  - [Not Available].

PMID- 15438265
TI  - [Fiftieth White House Conference on childhood and adolescence].

PMID- 15438264
TI  - [The efficiency of the medical service in child welfare work].

PMID- 15438266
TI  - [Protective treatment for the pregnant woman, in particular hormone, vitamin and
      anti-vitamin treatment].

PMID- 15438267
TI  - [Social aspects of dystrophy of nutritional origin in infants in Madras, India].

PMID- 15438268
TI  - [Prenatal prevention of infectious diseases and active immunization during early
      infancy].

PMID- 15438269
TI  - [Protective measure in the care of premature infants].

PMID- 15438270
TI  - [Centers for the newborn].

PMID- 15438271
TI  - [Prophylaxis against dental and parodontal diseases by observation of maxillo
      dental development].

PMID- 15438272
TI  - [Nutritional problems in social hygiene].

PMID- 15438273
TI  - [On the education of mothers and future mothers in the fight against infant
      mortality].

PMID- 15438274
TI  - [Has hospital cross-infection been conquered in the modern clinics and
      nurseries?].

PMID- 15438275
TI  - [Detection of incompatible blood factors in the parents].

PMID- 15438276
TI  - [The importance of genetic research in maternity hospitals].

PMID- 15438277
TI  - [The problem of the liver in the feeding of the child of pre-school or school
      age].

PMID- 15438278
TI  - [Abortions in the light of immunology and genetics].

PMID- 15438279
TI  - [Cybernetics or the analogies between man and machine].

PMID- 15438280
TI  - [Treatment of certain kidney diseases by testosterone].

PMID- 15438281
TI  - [Fibro-cystic adamantinomas].

PMID- 15438282
TI  - [The limits of efficiency of industrial medicine in small cities].

PMID- 15438284
TI  - [Relations with social security].

PMID- 15438283
TI  - [Diseases of welders; study of 216 medical case histories].

PMID- 15438285
TI  - [Two little known clinical signs of silicosis].

PMID- 15438286
TI  - [Arsine poisoning in boiler scaling with acids].

PMID- 15438287
TI  - [Neurological review].

PMID- 15438288
TI  - [Twenty-one years of electroencephalography].

PMID- 15438289
TI  - [Review of pediatric medicine].

PMID- 15438291
TI  - [Treatment of acute meningitis in the child].

PMID- 15438290
TI  - [Accelerated or explosive dentition; role of hypervitaminosis D].

PMID- 15438292
TI  - [Egyptian splenomegaly; case of Egyptian splenomegaly due to Schistosoma
      haematobium].

PMID- 15438293
TI  - [Ophthalmology in Madagascar, region of the high plateaus].

PMID- 15438294
TI  - [First report on the composition of cow's milk and cow-buffalo milk at
      Pondichery].

PMID- 15438295
TI  - [The anterior humeral route].

PMID- 15438297
TI  - [Chemico-legal expert opinion in the French Indies from 1934 to 1949].

PMID- 15438296
TI  - [Two cases of amebic hepatitis treated by conessine chlorhydrate].

PMID- 15438298
TI  - [Exanthematic boutonneuse fever of the Congo; considerations on its
      symptomatology].

PMID- 15438299
TI  - [Combination of mel B and novocaine].

PMID- 15438300
TI  - [Mixture of mel B and novocaine in solution in dimethylacetamide].

PMID- 15438301
TI  - [Combination of mel B and para-aminobenzoic acid].

PMID- 15438302
TI  - [Serodiagnosis of typhoid fever in the army].

PMID- 15438303
TI  - [Malignant ulcerous syphilis after penicillin therapy].

PMID- 15438304
TI  - [Bilateral goundou of the malar bones seen in a native of Ubangi].

PMID- 15438306
TI  - [Fevers of the typhus group].

PMID- 15438305
TI  - [Case of stubborn cutaneous staphylococcic infection treated with aureomycin].

PMID- 15438307
TI  - Anxiety.

PMID- 15438309
TI  - Treatment of venereal diseases.

PMID- 15438308
TI  - Diagnostic aids in coronary disease using exercise with multiple chest leads.

PMID- 15438310
TI  - Cholecystocolic fistula; report of a case.

PMID- 15438311
TI  - Albert Freeman Africanus King (1841-1914); his theory as to the transmission of
      malaria by mosquitoes.

PMID- 15438312
TI  - Every hospital a teaching hospital.

PMID- 15438313
TI  - The law and your prescriptions.

PMID- 15438314
TI  - BRIDGEMASTER.

PMID- 15438315
TI  - PILLDRIVER.

PMID- 15438317
TI  - WHERE to keep your spare cash.

PMID- 15438316
TI  - SOAPLANDER.

PMID- 15438318
TI  - NATION'S incomes holding high.

PMID- 15438319
TI  - WILL you be called into service?

PMID- 15438321
TI  - U.S. PHYSICIANS: where they're going; percentage of gain or loss in physician
      population during the last twelve years, by states.

PMID- 15438320
TI  - CARE and feeding of your files.

PMID- 15438322
TI  - Handling the cantankerous patient.

PMID- 15438323
TI  - TRY imagination on your walls.

PMID- 15438325
TI  - Group practice--is it for you?

PMID- 15438324
TI  - Have you the right kind of deed?

PMID- 15438326
TI  - WHAT'S in the Wolverton Health Bill.

PMID- 15438327
TI  - Doctors fight hospital 'extortion'.

PMID- 15438328
TI  - THEY budget patients' health costs.

PMID- 15438330
TI  - HOW businesslike should a doctor be?

PMID- 15438329
TI  - REPLY to the "loyal opposition.".

PMID- 15438331
TI  - Time to expose the economic quack.

PMID- 15438333
TI  - THIS press code really pays off.

PMID- 15438332
TI  - LIBRARY service by mail.

PMID- 15438334
TI  - OPEN letter from a doctor's wife.

PMID- 15438335
TI  - What we can learn from cultists.

PMID- 15438336
TI  - The modern treatment of acute nephritis in children.

PMID- 15438337
TI  - Vertigo from the general practitioner's point of view.

PMID- 15438338
TI  - The treatment of rheumatoid arthritis.

PMID- 15438339
TI  - Infective hepatitis.

PMID- 15438340
TI  - The management of hypertension.

PMID- 15438341
TI  - Some reflections on tuberculosis.

PMID- 15438342
TI  - Diagnosis of acute intussusception in infants.

PMID- 15438343
TI  - Recent advances in the treatment of heart disease.

PMID- 15438344
TI  - Indications for, and prognosis in surgical treatment of gastric and duodenal
      ulcers.

PMID- 15438345
TI  - Modern trends in spinal anaesthesia.

PMID- 15438346
TI  - Fibroids of the uterus.

PMID- 15438347
TI  - In vitro estimation of sensitivity of Mycobacterium tuberculosis to
      chemotherapeutic agents.

PMID- 15438348
TI  - Armed services medical equipment maintenance course.

PMID- 15438350
TI  - The neuropsychiatric ward technician.

PMID- 15438349
TI  - Dishwashing detergent dispensers.

PMID- 15438351
TI  - Chemical and biologic reactions involved in the chlorination of water.

PMID- 15438352
TI  - Cutaneous tuberculosis and its treatment with calciferol.

PMID- 15438353
TI  - Governor Thomas E. Dewey of New York on socialized medicine.

PMID- 15438354
TI  - Report of conference on terramycin.

PMID- 15438356
TI  - MEDICAL women of North Carolina.

PMID- 15438355
TI  - A rewarding activity for women physicians, the family clinic.

PMID- 15438357
TI  - Case reports; tumor of brain.

PMID- 15438358
TI  - Some psychiatric problems in general practice; special forms of treatment; psycho
      therapeutic procedures.

PMID- 15438359
TI  - The home management of the tuberculous patient.

PMID- 15438360
TI  - Doctor William Smith.

PMID- 15438361
TI  - The significance and distribution of blood group and rhesus factor among the
      Ewes.

PMID- 15438362
TI  - DIGITALIS therapy in varicose eczema and ulceration.

PMID- 15438363
TI  - DECISION given by the Industrial Injuries Commissioner on a claim for benefit
      under the National Insurance (Industrial Injuries) Acts, 1946 and 1948.

PMID- 15438364
TI  - John Lambe.

PMID- 15438365
TI  - [Rural sanitary problems].

PMID- 15438366
TI  - [Clinical anthropology and psychotherapy in contemporary society].

PMID- 15438367
TI  - [Treatment of whooping cough with chloromycetin].

PMID- 15438368
TI  - [Acoustic prosthesis; orientation for the general practitioner].

PMID- 15438369
TI  - [Myiasis linearis (larva migrans) in an infant].

PMID- 15438370
TI  - [Chronic articular rheumatism and streptomycin].

PMID- 15438371
TI  - [Clinical urological note].

PMID- 15438372
TI  - [Anti-tuberculosis campaigns in rural districts].

PMID- 15438373
TI  - [Spain and the discovery of quinine].

PMID- 15438374
TI  - [Carcinoma of the lung].

PMID- 15438375
TI  - [Site of formation of renin in the kidney].

PMID- 15438376
TI  - [Study of experimental tuberculosis re-infection in animals treated with
      streptomycin].

PMID- 15438377
TI  - [Diabetes mellitus in a five-month-old child].

PMID- 15438378
TI  - [Peptic ulcer of the esophagus; short esophagus; resection and esophago
      gastrostomy].

PMID- 15438379
TI  - [Malignant thymoma; radiological examination of the anterior mediastinum].

PMID- 15438380
TI  - [A new sympathico adrenolytic; dihydroderivatives of lysergic acid].

PMID- 15438381
TI  - [Biochemical and physiological diagnosis of cancer].

PMID- 15438382
TI  - [Nephroureteral colic].

PMID- 15438383
TI  - [Surgical treatment of fractures of the internal malleolus].

PMID- 15438384
TI  - [Manual extraction of the placenta; 431 cases].

PMID- 15438385
TI  - [A case of ileocecal invagination].

PMID- 15438386
TI  - [Interesting case of a pseudocyst of the pancreas following biliary lithiasis
      with cholecystitis].

PMID- 15438387
TI  - [Pedro Martir de Angleraa, his personality and his testimony].

PMID- 15438388
TI  - [Preliminary note on the isolation and cultivation in Mexico of a
      Schizotrypanum].

PMID- 15438389
TI  - [Nutritive value of the tortilla fortified with soy bean].

PMID- 15438390
TI  - [New sulfur compound in dermatology].

PMID- 15438391
TI  - [Hexachlorocyclohexane and its effect on the common dog tick in Mexico;
      laboratory tests; preliminary report].

PMID- 15438392
TI  - [Treatment of bronchial asthma with medicinal aerosols].

PMID- 15438393
TI  - [History of medicine in Colombia; first abdominal operations].

PMID- 15438394
TI  - [Lipid pneumonia; a case with necropsy and review of bibliography].

PMID- 15438395
TI  - [Experimental heart disease from trypanosomiasis].

PMID- 15438396
TI  - [Short method and several considerations on practical cholesterometry].

PMID- 15438397
TI  - [BCG vaccination; intestinal absorption of BCG and the tuberculigenic power of
      the bacillus contained in the organs of the test animals and vaccinated
      children].

PMID- 15438398
TI  - [Divulgation of hygiene and medicine].

PMID- 15438399
TI  - [Treatment of typhoid fever with chloroquine diphosphate; preliminary note].

PMID- 15438400
TI  - [Antibodies against Treponema carateum of pinta in the blood serum of pinta
      patients].

PMID- 15438401
TI  - [Total cystectomy in cancer of the bladder].

PMID- 15438402
TI  - [Mario Donati Foundation in Mexico].

PMID- 15438403
TI  - [Soil conservation and popular nutrition].

PMID- 15438404
TI  - [Diagnosis and treatment of nephrolithiasis].

PMID- 15438405
TI  - [Tumors of the bladder].

PMID- 15438406
TI  - [Present state of the poliomyelitis problem on the American hemisphere].

PMID- 15438407
TI  - [Epidemiological study of amebiasis with reference to Colombia].

PMID- 15438408
TI  - [Clinical case of pleurisy due to Endamoeba histolytica].

PMID- 15438409
TI  - [The sage Mutis and medicine in Santa Fe during the viceroyship].

PMID- 15438410
TI  - [Deep radiotherapy in cancer of the larynx].

PMID- 15438411
TI  - [Use of the sphygmomanometer in medical and surgical practice].

PMID- 15438412
TI  - [Tuberculous infection and disease].

PMID- 15438413
TI  - [Post-traumatic fat embolism].

PMID- 15438414
TI  - [Clinico-medical note; thrombopathy due to arsenic].

PMID- 15438415
TI  - [Clinico-surgical note; epiploitis].

PMID- 15438416
TI  - [Pyelectasis].

PMID- 15438417
TI  - [Pirogoff's osteoplastic amputation].

PMID- 15438418
TI  - [Urological semeiology in children].

PMID- 15438419
TI  - [Contact dermatitis caused by a plastic watch strap].

PMID- 15438420
TI  - [Pulmonary resection in the treatment of bronchiectasis].

PMID- 15438421
TI  - [Intraligamentous pregnancy; a personal case].

PMID- 15438422
TI  - [Radiotherapy of cancer of the mouth].

PMID- 15438424
TI  - [Case of intracranial carotido-cavernous sinus aneurysm].

PMID- 15438423
TI  - [Fundus oculi in pregnancy; chronic and acute retinosis in pregnancy].

PMID- 15438425
TI  - [Mycological notes. III. Genus Trichophyton; general characteristics and study of
      the species].

PMID- 15438426
TI  - [New investigations on granulo-diagnosis].

PMID- 15438427
TI  - [Hemiplegic syndrome following treatment by antabuse in a case of chronic
      alcoholism].

PMID- 15438428
TI  - [The heart in anemia].

PMID- 15438429
TI  - [Errors in the administration of antibiotics].

PMID- 15438430
TI  - [Stenosis of the aortic isthmus].

PMID- 15438431
TI  - [Hepatic insufficiency and liver function tests].

PMID- 15438432
TI  - [Aviation medicine in the U.S. Air Force].

PMID- 15438433
TI  - [Absenteeism].

PMID- 15438434
TI  - [Obstetric risks and their relation to work].

PMID- 15438435
TI  - [Polarographic investigation of lead in the blood].

PMID- 15438436
TI  - [Treatment of athlete's foot].

PMID- 15438437
TI  - Changes in the lungs produced by natural graphite.

PMID- 15438438
TI  - [Organization of medical services of the Industrial Social Service].

PMID- 15438439
TI  - [Fifteen years of industrial medicine].

PMID- 15438440
TI  - [Reforms of the Argentine law on industrial accidents].

PMID- 15438441
TI  - [Benzene poisoning in Argentina].

PMID- 15438442
TI  - [The diver and his selection].

PMID- 15438443
TI  - [Savings and insurance, methods for obtaining the well-being of the worker].

PMID- 15438444
TI  - [Theory and results of a method of selecting industrial workers].

PMID- 15438445
TI  - [Echinococcosis as an occupational disease].

PMID- 15438446
TI  - [Color contrasts of the surroundings and industrial fatigue].

PMID- 15438447
TI  - [Pathology of farmers].

PMID- 15438448
TI  - [The human factor and industrial accidents].

PMID- 15438449
TI  - [Mycoses and occupational diseases].

PMID- 15438450
TI  - POSITION and duties of the works medical officer.

PMID- 15438451
TI  - [Employment of seriously disabled workers].

PMID- 15438452
TI  - [Bicycle racing for minors].

PMID- 15438453
TI  - [Raynaud's syndrome due to vibrations; traumatic spasmodic arteritis].

PMID- 15438454
TI  - [Pneumoconiosis; review of 717 cases of pulmonary silicosis].

PMID- 15438456
TI  - [The expert physician in industrial law].

PMID- 15438455
TI  - [Medical assistance and disability compensation under social security].

PMID- 15438457
TI  - POSITION and duties of the works medical officer.

PMID- 15438458
TI  - [Problem of health in rural labor].

PMID- 15438459
TI  - [Cholecystitis without calculi].

PMID- 15438460
TI  - [Antibiotic treatment of Malta fever].

PMID- 15438461
TI  - [Study of proteins in syphilitic serum; proteins in tertiary and latent
      syphilis].

PMID- 15438462
TI  - [Mechanism of action of short waves in bronchial asthma].

PMID- 15438463
TI  - [Arnstein disease].

PMID- 15438464
TI  - [Tetany syndrome during typhoid].

PMID- 15438465
TI  - [A case of cutaneous leishmaniasis in the province of Murcia, cured by cibazol].

PMID- 15438466
TI  - [Nephrolithiasis in congenital solitary kidney].

PMID- 15438467
TI  - [Treatment of metrorrhagia with synthetic antihistamines].

PMID- 15438468
TI  - [Cysts of the pancreas].

PMID- 15438469
TI  - [Recent studies on lead poisoning in Italy].

PMID- 15438470
TI  - [Further observations on an American re-elaboration of the Velicogna
      piezoelectric hypothesis of the pathogenesis of silicosis].

PMID- 15438471
TI  - [Prevention of occupational dermatoses in a Lombardy machine shop with the use of
      barrier creams].

PMID- 15438472
TI  - [Deafness as a social problem].

PMID- 15438473
TI  - [Hygiene in schools].

PMID- 15438474
TI  - [Social aspects of rheumatism].

PMID- 15438475
TI  - [Local anesthesia].

PMID- 15438476
TI  - [Chemistry and physiology of vitamins].

PMID- 15438478
TI  - Medical modeling in wax.

PMID- 15438477
TI  - Diarrhoea in infancy and childhood.

PMID- 15438479
TI  - Subluxation of the shoulder joint in chronic rheumatoid arthritis.

PMID- 15438480
TI  - 'Luotest' a preliminary evaluation in the diagnosis of late syphilis.

PMID- 15438481
TI  - Contact tracing; venereal diseases in Africa.

PMID- 15438482
TI  - A case of skin graft over osteomyelitis with sequestrum formation.

PMID- 15438483
TI  - ADRENAL gland in human disease.

PMID- 15438484
TI  - The clinical thermometer.

PMID- 15438485
TI  - Lepra.

PMID- 15438486
TI  - [Roentgenography and roentgen photography].

PMID- 15438488
TI  - [Weltmann's test in differential diagnosis of subacute bacterial and progressive
      rheumatic endocarditis].

PMID- 15438487
TI  - [Treatment of tuberculosis of the kidneys].

PMID- 15438489
TI  - [Histamine; effect, administration and dosage in allergy].

PMID- 15438490
TI  - [Neurodermatitis].

PMID- 15438491
TI  - [Treatment of rheumatic fever].

PMID- 15438492
TI  - [Painless labor].

PMID- 15438493
TI  - [Prevention of dental caries in youth].

PMID- 15438494
TI  - Vitamin B12.

PMID- 15438495
TI  - [Plummer-Vinson's syndrome].

PMID- 15438497
TI  - [Control of rheumatism in France].

PMID- 15438496
TI  - [New legislation on social insurance in relation to physicians].

PMID- 15438498
TI  - [Effect of physical culture on growth and development of children].

PMID- 15438499
TI  - [Effects of gamma globulin].

PMID- 15438501
TI  - [Painless labor].

PMID- 15438500
TI  - [Antihistamines].

PMID- 15438502
TI  - [Heat stroke].

PMID- 15438503
TI  - [Planning for 1951].

PMID- 15438504
TI  - [Legislations in the field of pharmacology in Yugoslavia].

PMID- 15438505
TI  - [Our oldest pharmacies].

PMID- 15438506
TI  - [Central paralysis; treatment and care of patients].

PMID- 15438508
TI  - [Technic, dosage and method of ultraviolet ray therapy].

PMID- 15438507
TI  - [Results of the modern treatment of cancer].

PMID- 15438509
TI  - [Feeding of infants in first year of life].

PMID- 15438510
TI  - [Helminthiasis and its control].

PMID- 15438511
TI  - [Political education of nurses].

PMID- 15438512
TI  - [Vera Porfir'evna Krylova].

PMID- 15438513
TI  - [Control of gastro-intestinal diseases].

PMID- 15438514
TI  - [Contemporary methods of treatment of bacillary dysentery].

PMID- 15438515
TI  - [Treatment of dysentery in children and care of patients].

PMID- 15438516
TI  - [Mastitis (inflammation of the mammary gland)].

PMID- 15438517
TI  - [Cracked nipple].

PMID- 15438518
TI  - [Nurses of the pioneer camp].

PMID- 15438519
TI  - [Etiology of eczema in infants and children].

PMID- 15438520
TI  - [Practical value of gonococcal culture].

PMID- 15438521
TI  - [Rapid method of determining erythrocyto sedimentation reaction].

PMID- 15438522
TI  - [Clinical aspects of harvest fever].

PMID- 15438523
TI  - [Recording the action current of the normal stomach; examination following test
      breakfast with the Tschermak-Schuster electrogastrograph].

PMID- 15438524
TI  - [Clinical significance of the direct diazo reaction of the serum bilirubin].

PMID- 15438525
TI  - [Treatment of Buerger's disease].

PMID- 15438526
TI  - [Goiter and hyperthyroidism].

PMID- 15438527
TI  - [Diagnosis and treatment of microsporia].

PMID- 15438528
TI  - [Supronalum therapy of erysipelas].

PMID- 15438529
TI  - [Increasing the effect of pyrogenic substances by simultaneous intravenous and
      intradermal administration].

PMID- 15438530
TI  - [Constitution and nutrition in diseases of the pancreas].

PMID- 15438531
TI  - [Further observations on the hydrochloric-acid-collargol serum reaction].

PMID- 15438532
TI  - [Exchange transfusion in fetal erythroblastosis with Braun's apparatus].

PMID- 15438533
TI  - [Vagotonias as a manifestation of primary adrenal insufficiency].

PMID- 15438534
TI  - [Treatment of orthostatic disturbances of circulation].

PMID- 15438535
TI  - [Diabetes mellitus and vascular disease; Kimmelstiel-Wilson disease].

PMID- 15438536
TI  - [Toxicology of pyramidon].

PMID- 15438537
TI  - [Treatment of paraungual and subungual panaris, subungual hematoma, and extensor
      surface furuncle].

PMID- 15438538
TI  - [Absence of intravascular coagulation or thrombus formation following injection
      of coagulant 733].

PMID- 15438539
TI  - [Stabilization of the sugar content of the cerebrospinal fluid with sodium
      fluoride].

PMID- 15438540
TI  - [Quantitative evaluation of the electrocardiogram; the ekagnost slide rule].

PMID- 15438541
TI  - [Endotracheal narcosis with curare in thoracic surgery].

PMID- 15438542
TI  - [Intestinal diverticulum as cause of ileus].

PMID- 15438543
TI  - [Diagnosis and therapy of epiphyseal coxa vara].

PMID- 15438544
TI  - [Symmetric contracture of the fingers as manifestation of a preuremic condition,
      and its differentiation from other contractures].

PMID- 15438545
TI  - [Critical observations on determination of prothrombin time].

PMID- 15438546
TI  - [Cortical osteoid].

PMID- 15438547
TI  - [Technic in intravenous injections].

PMID- 15438548
TI  - [Early diagnosis of obstruction due to invagination].

PMID- 15438549
TI  - [Static ultrasonic therapy with microdosage; contribution to technic, dosage and
      mechanism of ultrasonic therapy].

PMID- 15438550
TI  - [Surgical therapy of late abscess of the brain following injury].

PMID- 15438551
TI  - [Polamidon in surgery].

PMID- 15438553
TI  - [Modern tuberculosis therapy].

PMID- 15438552
TI  - [Experience with streptomycin].

PMID- 15438554
TI  - [Stuttgart canine distemper in humans in Frankfurt].

PMID- 15438555
TI  - [Treatment of disorders of the peripheral circulation with a new vasodilator].

PMID- 15438556
TI  - [Treatment of enterobiasis vermicularis with gentian violet].

PMID- 15438557
TI  - [Growth of typhoid and paratyphoid bacteria in acidulated milk].

PMID- 15438558
TI  - [Most suitable alternating frequencies in electroshock therapy].

PMID- 15438559
TI  - [Lipotropic substances in the treatment of liver disease].

PMID- 15438560
TI  - [Results of studies with Hochst's new depot-penicillin].

PMID- 15438561
TI  - [Critical observations on nitrogen mustard therapy].

PMID- 15438562
TI  - [Activation of pulmonary tuberculous processes in children following
      bronchography].

PMID- 15438563
TI  - [Mistakes and dangers in novocain injection].

PMID- 15438564
TI  - [Specific therapy of infectious disease with special reference to the use of
      blood of convalescents in transfusion].

PMID- 15438565
TI  - [Unimanual percussion].

PMID- 15438566
TI  - [Hematocytoid involutional forms of mould fungi].

PMID- 15438567
TI  - [Atypical pneumonia and infiltrates].

PMID- 15438568
TI  - [The limit of tolerance and sudden death].

PMID- 15438569
TI  - [Collateral effects of penicillin therapy].

PMID- 15438570
TI  - [Cranial osteomyelitis].

PMID- 15438571
TI  - [Hematocytoid involutional forms of mould fungi].

PMID- 15438572
TI  - [New synthetic analgesics with effect upon the central nervous system].

PMID- 15438573
TI  - [Concept of eczema as an example of the difficulty of establishing distinct
      medical classifications].

PMID- 15438574
TI  - [Clinical aspect of skin reactions in cancer].

PMID- 15438575
TI  - [Behavior of certain functions of the skin during parathyroid therapy].

PMID- 15438576
TI  - [Urethane therapy of mycosis fungoides].

PMID- 15438577
TI  - [Mercurochrome as a disinfectant and medicament of the skin].

PMID- 15438578
TI  - [Therapeutic effect of blood transfusion in hypoferric and hemorrhagic anemia].

PMID- 15438579
TI  - [Report on changes in the general state of health during the last 50 years].

PMID- 15438580
TI  - [Occurrence of cancer cells in expectoration].

PMID- 15438581
TI  - [Increasing thiosemicarbazone tolerance by means of levulose].

PMID- 15438582
TI  - [Efficacy of phenothiazine in the diagnosis and treatment of oxyuriasis].

PMID- 15438583
TI  - [Poisoning with a glycerine substitute, diethylene glycol].

PMID- 15438584
TI  - [Protocid therapy of coli-infection of the urinary tract].

PMID- 15438585
TI  - [Recent legislation affecting diathermy, short-wave and similar apparatuses].

PMID- 15438586
TI  - [Results of recent research on so-called prostatic hypertrophy and cancer].

PMID- 15438587
TI  - [Effect of health and nutrition upon mental capacity; a sociohygenic study of
      German school children in 1949].

PMID- 15438588
TI  - [Report on changes in the general state of health during the last 50 years].

PMID- 15438589
TI  - [Spread of poliomyelitis in Bavaria from 1937 to 1948].

PMID- 15438590
TI  - [Histotomy of the liver].

PMID- 15438591
TI  - [Are preparations of procaine penicillin for retarded action to be preferred to
      water-soluble preparations?].

PMID- 15438592
TI  - [Clinical masking of subacute bacterial endocarditis].

PMID- 15438593
TI  - [Obligation to undergo surgery].

PMID- 15438594
TI  - [Bibliography of German literature on antibiotics, 1949].

PMID- 15438595
TI  - [Prognosis in lipophil dystrophy].

PMID- 15438596
TI  - [Problem of the neuromuscular system of the lung].

PMID- 15438597
TI  - [Treatment of deficiency symptoms in natural and artificial climacteric with
      depot-estromon; a new principle in prolonged-action estrogen therapy].

PMID- 15438598
TI  - [Significant early and late manifestations of methylthiouracil intoxication and
      their prevention].

PMID- 15438599
TI  - [Prophylaxis of thromboembolism].

PMID- 15438600
TI  - [Penicillin therapy of ischialgia and herpes zoster].

PMID- 15438601
TI  - [Bilirubinuria induced by physical exertion and administration of choline during
      recovery from parenchymal jaundice].

PMID- 15438602
TI  - [Autogenic training in general practice].

PMID- 15438603
TI  - [Problem of the neuromuscular system of the lungs].

PMID- 15438604
TI  - [The heart during the orgasm].

PMID- 15438605
TI  - [Sleep therapy in influenza].

PMID- 15438606
TI  - [Treatment of abortion by the general practitioner].

PMID- 15438607
TI  - [Fatal poisoning with castrix (hydrochloride of 2-chlor-4-methyl-6
      dimethylaminopyrimidine), a rat poison].

PMID- 15438608
TI  - [Sketch on therapy of the circulatory system in old age].

PMID- 15438609
TI  - [Treatment of peritonsillar abscess].

PMID- 15438610
TI  - [Clinical aspect and care of extrapulmonary tuberculosis].

PMID- 15438611
TI  - [Problem of dosage in ultrasonic therapy].

PMID- 15438612
TI  - [Diagnosis and differential diagnosis of intervertebral disk hernia].

PMID- 15438613
TI  - [Synopsis of roentgenology of the normal pleura and of pleural endothelioma].

PMID- 15438614
TI  - [Prophylactic therapy of nocturnal attacks of asthma].

PMID- 15438615
TI  - [Recent observations on infusion therapy in jaundice].

PMID- 15438616
TI  - [Determination of serum bilirubin in the clinical laboratory].

PMID- 15438617
TI  - [New method in control of oxyuriasis].

PMID- 15438618
TI  - [Treatment of tuberculosis of the skin with massive doses of vitamin D2].

PMID- 15438619
TI  - [Xanthomatous biliary cirrhosis].

PMID- 15438620
TI  - [Physico-chemical basis of electrophoresis].

PMID- 15438621
TI  - [History of the concept of neurosis].

PMID- 15438622
TI  - [Diagnosis and treatment of cancer of the lung].

PMID- 15438623
TI  - [Therapeutic use of organic fluorine compounds].

PMID- 15438624
TI  - [A survey on the nature and properties of antithrombin].

PMID- 15438625
TI  - [Psychotherapy of peptic ulcer].

PMID- 15438626
TI  - [Occupational disease in the rubber industry].

PMID- 15438627
TI  - [Streptomycin therapy of tuberculous meningitis].

PMID- 15438628
TI  - [Use of honey for intravenous injection].

PMID- 15438629
TI  - [Survey of sulfonamide toxicity with case reports].

PMID- 15438630
TI  - [Therapy resistant insulin shock].

PMID- 15438631
TI  - [Etiology of so-called epidemic hepatitis].

PMID- 15438632
TI  - [New methods in the treatment of epilepsy with glyboral-forte].

PMID- 15438633
TI  - [Pharmacologic and clinical studies of Retterspitzwasser, a proprietary
      cataplasm].

PMID- 15438634
TI  - [Attempted suicide with phanodorm-calcium].

PMID- 15438635
TI  - [Roentgen resistant lymphogranulomatosis treated with trichlorotriethylamine
      hydrochloride, with special reference to following modifications in the
      hemopoietic system].

PMID- 15438636
TI  - [Effect of intralumbar injections of formol toxoid in two cases of severe post
      diphtheritic paralysis].

PMID- 15438637
TI  - [Psychotherapy at the medical clinic].

PMID- 15438638
TI  - [Joseph L. von Auenbrugger, inventor of percussion, and its development after his
      death].

PMID- 15438639
TI  - [Siegfried J. Thannhauser on his 65th birthday].

PMID- 15438640
TI  - [Influenza as a cryopathy].

PMID- 15438642
TI  - [Diagnosis of carditis].

PMID- 15438641
TI  - [Pharmacology, toxicology and therapeutic use of snake venoms].

PMID- 15438643
TI  - [A practical method of early serological diagnosis of cancer].

PMID- 15438644
TI  - [Limitations and possibilities in clinical therapy of neuroses].

PMID- 15438645
TI  - [Modifications of the blood plasma induced by small parenteral doses of sugar
      solutions; contribution to the mechanism of sugar therapy].

PMID- 15438646
TI  - [Treatment of nocturnal enuresis with movellan (strychnine derivative)].

PMID- 15438647
TI  - [Psychotherapy or intelligent sympathy?].

PMID- 15438648
TI  - [Experiences with an effective therapy of nocturnal paresthetic brachialgia and
      other disorders of the peripheral circulation].

PMID- 15438649
TI  - [Sepsis and expert testimony in accidents].

PMID- 15438650
TI  - [Ideal laxative].

PMID- 15438651
TI  - [Resorption of conteben and p-aminosalicylic acid following intracavitary
      instillation].

PMID- 15438652
TI  - [Prophylactic and therapeutic use of dicumarines].

PMID- 15438653
TI  - [Expert testimony in dermatovenereology].

PMID- 15438654
TI  - [Myoma of the stomach].

PMID- 15438655
TI  - [Clinical aspect of calcinosis interstitialis universalis].

PMID- 15438656
TI  - [Abuse of polamidon].

PMID- 15438657
TI  - [Constitutional variations in regulation].

PMID- 15438658
TI  - [In memory of Paul Gottlieb Werlhof].

PMID- 15438659
TI  - [Source of the hospital's drug supply].

PMID- 15438660
TI  - [Herbert Assmann].

PMID- 15438662
TI  - [Not Available].

PMID- 15438661
TI  - [The new Elbe incubator].

PMID- 15438663
TI  - [Beotron 366 P hearing aid].

PMID- 15438664
TI  - [Food for thought concerning the manufacture of trusses, and a new type of
      truss].

PMID- 15438665
TI  - [Unusual apparatus for elongation of extremities].

PMID- 15438666
TI  - [Musculature of the leg from pelvis to foot].

PMID- 15438667
TI  - [Your calling; an address to orthopedic students].

PMID- 15438668
TI  - [Physician and orthopedic technician in the service of the sick].

PMID- 15438669
TI  - [A sunchine-alley for ultraviolet irradiation].

PMID- 15438670
TI  - [Not Available].

PMID- 15438672
TI  - [Construction of prostheses].

PMID- 15438671
TI  - [Apparatus for control of blood pressure and pulse during operations].

PMID- 15438673
TI  - [The standing, walking and bending Hirsch knee].

PMID- 15438674
TI  - [The Kuhlmann-Richter arm, a combined esthetic and practical prosthesis].

PMID- 15438675
TI  - [Unusual prostheses; improved prosthesis for a congenital deformity].

PMID- 15438676
TI  - [Skin grafts].

PMID- 15438677
TI  - [Late result of postoperative tetany treated with AT 10].

PMID- 15438678
TI  - [Residual subperitoneal pelvic cysts in the hysterectomized].

PMID- 15438679
TI  - [Large fecaloma at the level of an acquired megarectosigmoid; subtotal resection
      of the rectosigmoid; recovery].

PMID- 15438680
TI  - [Three cases of ideal one-stage colectomy for cancer of the left colon].

PMID- 15438681
TI  - [Congenital dilatation of the common bile duct].

PMID- 15438682
TI  - [Operative management of a high abdominal aorticocaval fistula].

PMID- 15438683
TI  - [Muscle grafts in the treatment of bronchopleural fistulas].

PMID- 15438684
TI  - [Late complications of bullets lodged in the lung].

PMID- 15438685
TI  - [Cancer of the cervical stump remaining after conservative hysterectomy for
      fibroma].

PMID- 15438686
TI  - [Acute staphylococcic duodenojejunitis following chronic osteomyelitis].

PMID- 15438687
TI  - [Terminal ileitis treated with streptomycine; recovery].

PMID- 15438688
TI  - [Proteins of the stomach wall].

PMID- 15438689
TI  - [Blood banks].

PMID- 15438690
TI  - [Non-operative treatment of perforated ulcers].

PMID- 15438691
TI  - [Cancer of the cervicothoracic portion of the esophagus operated by a cervical
      incision and left thoracophrenolaparotomy].

PMID- 15438692
TI  - [Tiered volvulus of the colon].

PMID- 15438693
TI  - [Tuberculous adenopathy apparently of primary infection simulating a tumor of the
      head of the pancreas].

PMID- 15438694
TI  - [Jejunal peptic ulcer following gastroenterostomy for ulcer; extensive
      gastrectomy with exclusion of the ulcer].

PMID- 15438695
TI  - [Generalized scleroderma with arthropathy; removal of 2 parathyroids; results
      after 4 years].

PMID- 15438696
TI  - [Treatment of perforated ulcers by continuous gastric aspiration].

PMID- 15438697
TI  - [Non-operative treatment of perforated gastroduodenal ulcers].

PMID- 15438698
TI  - [Treatment of intestinal invagination].

PMID- 15438699
TI  - [Blood transfusions and blood banks].

PMID- 15438700
TI  - [Our experience with tissue therapy (Filatov method) in 150 cases].

PMID- 15438702
TI  - [Epitheliomas developing on facial inclusions].

PMID- 15438701
TI  - [Streptomycin in the treatment of tuberculosis of the female genitals].

PMID- 15438703
TI  - [A case of rectovesical impalement].

PMID- 15438704
TI  - [Sinocarotid complications following subtotal thyroidectomy for exophthalmic
      goiter].

PMID- 15438705
TI  - [Severance of the anterior tibial nerve at the upper portion of the leg;
      secondary suture on the 60th day; cure].

PMID- 15438706
TI  - [One-stage duodenopancreatectomy for cancer of the head of the pancreas; cure;
      one-stage duodenopancreatectomy for cancer of Vater's ampulla and gastric ulcer].

PMID- 15438707
TI  - [2 cases of endometriosis of the small intestine].

PMID- 15438708
TI  - [Malignant transformation of tumors in myeloplaxia].

PMID- 15438710
TI  - [Blood banks].

PMID- 15438709
TI  - [Palliative subaortic esogastric anastomosis by high left thoracophrenolaparotomy
      for inoperable midthoracic cancer of the esophagus].

PMID- 15438711
TI  - [Case of megacolon due to vertebral malformation].

PMID- 15438712
TI  - [Very large cyst; benign tumors of the esophagus: case report of a leiomyoma].

PMID- 15438713
TI  - [Stenosis of the extrahepatic biliary ducts and cutaneous biliary fistulas].

PMID- 15438714
TI  - [Osteolytic forms of osseous myeloplaxic tumors].

PMID- 15438715
TI  - [Diaphragmatic hernia due to a bullet; strangulated diaphragmatic hernia due to a
      knife wound].

PMID- 15438716
TI  - [Strangulated diaphragmatic hernia; preoperative clinical and radiological
      diagnosis; surgery by the thoracic route; cure].

PMID- 15438717
TI  - [Total colectomy].

PMID- 15438718
TI  - [Organization of blood transfusion, in the Paris region, in the departmental,
      city and hospital plan].

PMID- 15438719
TI  - [Examination of the epidural space with lipiodol in sciatica and lumbago].

PMID- 15438720
TI  - [Procedures in cholangiography during laparotomy].

PMID- 15438721
TI  - [Examination of the epidural space with lipiodol in the diagnosis of
      lumbosciatica].

PMID- 15438722
TI  - [Blood banks].

PMID- 15438723
TI  - [Cord phlebitis of the deltopectoral groove].

PMID- 15438724
TI  - [Intermittent tumor of the ovary, uterine aplasia and atresia of the vagina in a
      girl aged 18].

PMID- 15438725
TI  - [Hepatic periarterial sympathectomy in the treatment of certain cases of icterus
      due to hepatitis].

PMID- 15438726
TI  - [Stricture of the lower esophagus; therapy by resection after a 10 year history].

PMID- 15438727
TI  - [Treatment of hydatid cysts of the lung; is excision of cyst and its adventitia
      possible?].

PMID- 15438728
TI  - [3 observations on uterine placentomas].

PMID- 15438729
TI  - [Bone banks; homologous bone grafts; study of 128 cases].

PMID- 15438730
TI  - [Spontaneous hemoperitoneum due to rupture of a primary epithelioma of the liver;
      partial hepatectomy; cure].

PMID- 15438731
TI  - [The organization of a regional blood transfusion center].

PMID- 15438733
TI  - [Upper median sternotomy in the treatment of mediastinal tumors; 7 personal
      cases].

PMID- 15438732
TI  - [Supernumerary spleen with twisted pedicle].

PMID- 15438734
TI  - [A rehabilitation center].

PMID- 15438735
TI  - [Surgical treatment of hepatitis].

PMID- 15438736
TI  - [Treatment of hydatid cyst of the lung, 80 cases; surgical treatment of pulmonary
      hydatidosis].

PMID- 15438737
TI  - [Early systematic examination for cancer of the uterus by vaginal smears; results
      of 6 months' practice].

PMID- 15438738
TI  - [Treatment of primary stage cancer of the cervix].

PMID- 15438739
TI  - [Streptomycin and tuberculosis of the adnexa].

PMID- 15438740
TI  - [Treatment of uncomplicated hydatid cysts of the lung; enucleation in the free
      pleura without opening of the cyst].

PMID- 15438741
TI  - [Results after 21 months of an anastomosis of the portal vein and the vena cava].

PMID- 15438742
TI  - [Studies on the development of Vibrio desulfuricans in aerobic media].

PMID- 15438743
TI  - [Reactions of decomposition and synthesis in lipolysis by sulfate-reducing
      bacteria].

PMID- 15438744
TI  - [Vegetation zones of mountains and their effect upon soil bacteria].

PMID- 15438745
TI  - [Bacteria mineralizing organic compounds of phosphorus].

PMID- 15438746
TI  - [Rhizophlyctis rosea, a micochytrid capable of destroying soil cellulose].

PMID- 15438747
TI  - [Formation of acetoin and 2,3-butylglycol with the culture of Aerobacter
      aerogenes].

PMID- 15438748
TI  - [Water content and certain properties of yeasts, growing in media with various
      contents of sodium chloride].

PMID- 15438749
TI  - [Anaerobic regeneration of flax retting and fluid and methods for speeding the
      process].

PMID- 15438750
TI  - [Bacteriophage in the production of cheese; resistance of streptococcus lactis to
      cheese bacteriophage].

PMID- 15438751
TI  - [Obtention of a jaundice-free strain of silkworms].

PMID- 15438753
TI  - [In memoriam. N. F. Gamaleia].

PMID- 15438752
TI  - [Theoretic significance of V. S. Butkevich's research in transformation of
      proteic substances in plant organisms and in the chemistry of the formation of
      organic acids].

PMID- 15438754
TI  - [Electron diffraction and electron microscopic studies of the structure of
      mechanically and electrolytically polished surfaces; problem of the so-called
      Beilby layer].

PMID- 15438756
TI  - [Technic in karyometry of tissue cultures].

PMID- 15438755
TI  - [Observations on dye absorption of anthocyanigerous cells].

PMID- 15438757
TI  - [Demonstration of the changes produced by heat on meat with Van Gieson staining].

PMID- 15438758
TI  - [Anti-reflection treatment in microscopy].

PMID- 15438759
TI  - [Hematexodia under the electron microscope].

PMID- 15438760
TI  - [Vital fluorochromization with acridine orange].

PMID- 15438761
TI  - [Polymorphism].

PMID- 15438762
TI  - [The heating-stage microscope and its accessories].

PMID- 15438763
TI  - [Observations on Vickers micro-hardness in calcite].

PMID- 15438764
TI  - Electropolishing apparatus for metallographic purposes.

PMID- 15438765
TI  - [Specific dye-etching of iron-silicon alloys; a new, rapid method for analysis of
      high-percentage iron-silicon alloys].

PMID- 15438766
TI  - [A new spectrum projector].

PMID- 15438767
TI  - [Not Available].

PMID- 15438768
TI  - [Psychiatric aspects of military desertion].

PMID- 15438769
TI  - [Wartime contribution of the U.S. Army Medical Corps].

PMID- 15438770
TI  - Etiology, symptomatology, and therapy of aphthous stomatitis.

PMID- 15438771
TI  - The minor hemorrhages of late pregnancy.

PMID- 15438772
TI  - Shall I write?

PMID- 15438773
TI  - Preventive medicine in Austria; a post war report.

PMID- 15438774
TI  - Toxic hepatitis presumably produced by massive prolonged ingestion of atabrine: a
      case report with autopsy findings.

PMID- 15438775
TI  - Tantalum gauze hernioplasty.

PMID- 15438776
TI  - Tularemia: ulceroglandular type with pneumonia; a case report.

PMID- 15438777
TI  - Sojourn in Zamboanga; expedition to Basilan, cattle boat inspection, foreign
      "invasion".

PMID- 15438778
TI  - The concept of "acceptance" in physical rehabilitation.

PMID- 15438779
TI  - [Pathology of the embryo due to infectious diseases in pregnancy].

PMID- 15438780
TI  - [Grave malformation in a newborn with congenital syphilis].

PMID- 15438781
TI  - [Fetal meningoencephalitis and maternal parotitis].

PMID- 15438782
TI  - [Pathology of the embryo probably due to rubella in the third month of
      pregnancy].

PMID- 15438783
TI  - [Repercussions on the newborn of infectious diseases of the mother during
      pregnancy; clinico-anamnestic research on a group of deaf-mutes and congenitally
      blind].

PMID- 15438784
TI  - [Incidence of maternal exanthematic diseases in abnormalities].

PMID- 15438785
TI  - [Retrospect diagnosis of deafness caused by maternal rubella through the study of
      audiograms].

PMID- 15438786
TI  - [Pregnancy and multiple sclerosis].

PMID- 15438787
TI  - [Genotypic diseases of the embryo].

PMID- 15438788
TI  - [Clinico-statistical data on fetal malformations observed in the Maternity
      Hospital and commune of Novara in the last 20 years].

PMID- 15438789
TI  - [Radiological diagnosis of fetal malformation and action of roentgen rays on the
      fetus].

PMID- 15438790
TI  - [Liver disease in the child of a mother with infectious hepatitis during
      pregnancy].

PMID- 15438791
TI  - [Analgesia in labor with the saddle block technic associated with induced labor].

PMID- 15438792
TI  - [Action of corticosterone, stilbene and testosterone on histaminic hypothermia].

PMID- 15438793
TI  - [Standards of care adopted by the Maternity Hospital of Novara for immature,
      premature and congenitally weak newborn].

PMID- 15438794
TI  - [Single dose and slow absorption folliculin therapy in the treatment of premature
      infants].

PMID- 15438795
TI  - [Clinico-statistical considerations on immature and premature infants at the
      Maternity Hospital of Novara in the past 20 years].

PMID- 15438796
TI  - [Surgical therapy of goiter in pregnancy].

PMID- 15438797
TI  - [Pre- and postoperative biological treatment].

PMID- 15438798
TI  - [Water metabolism and pregnancy].

PMID- 15438799
TI  - [Action of thiouracil on the thyroid and pituitary in normal conditions and after
      pituitary block by estrogens].

PMID- 15438800
TI  - [Factors responsible for abortion in experimental scurvy].

PMID- 15438801
TI  - [Methods of temporary approximation of the peritoneal edges in conservative
      suprasymphysial cesarean section with exclusion of the peritoneal cavity].

PMID- 15438802
TI  - [Thionine in the treatment of dysfunctional menometrorrhagia].

PMID- 15438803
TI  - [Use of deamin in labor].

PMID- 15438804
TI  - [The science of genetics].

PMID- 15438805
TI  - [Leptomeningeal hemorrhage].

PMID- 15438806
TI  - [Therapeutic use of lipocaic].

PMID- 15438807
TI  - [Diagnosis of pregnancy by chemical determination of gonadotropins].

PMID- 15438808
TI  - [Muscular miopragia in the course of Basedow's disease].

PMID- 15438809
TI  - [A case of hemorrhagic encephalopathy following prolonged dicumarol therapy].

PMID- 15438810
TI  - [Heart-lung machine].

PMID- 15438811
TI  - [First-aid in superficial uncomplicated wounds].

PMID- 15438812
TI  - [The science of genetics].

PMID- 15438813
TI  - [Were our ancestors steatopygous or callipygous?].

PMID- 15438814
TI  - [Rapid craniology for radiological use].

PMID- 15438815
TI  - [Associated thermometric tests in the study of obliterative arteriopathy].

PMID- 15438816
TI  - [Penetration and adsorption of aerosols].

PMID- 15438817
TI  - [Pleural adhesions; physiopathology, etiology, pathological anatomy,
      classification].

PMID- 15438818
TI  - [Collection of laws relative to the professional orders].

PMID- 15438819
TI  - [Lipotropic therapy of liver disease].

PMID- 15438820
TI  - [Influence of the ventricular systole on the sinus rhythm in complete
      auriculoventricular dissociation; electrocardiographic research].

PMID- 15438821
TI  - [A case of early deep periodontitis].

PMID- 15438822
TI  - [Chronic fistulized pleural empyema and surgical therapy].

PMID- 15438823
TI  - [Association of para-amino-salicylic acid and pneumothorax in the treatment of
      caverns of primarily biological character].

PMID- 15438824
TI  - [Pendulous adhesions in cavity of pneumothorax].

PMID- 15438826
TI  - [Non-tuberculous transitory infiltrations of the lung].

PMID- 15438825
TI  - [Myocardial inotropism of zones and subsidiary measures of digitalis; clinical
      and roentgenkymographic pictures].

PMID- 15438828
TI  - [World Health Organization; its activity during 1949; plans for 1951].

PMID- 15438827
TI  - [Ten commandments of the gynecologist for control of genital cancer in women].

PMID- 15438829
TI  - [Surgical pathology in theory, teaching and practice].

PMID- 15438830
TI  - [Heparin in the complex of factors of blood coagulation and thrombosis].

PMID- 15438831
TI  - [Treatment of chronic polyarthritis with desoxycorticosterone and ascorbic acid
      (the Lewin and Wassen method); proposal of a referendum on results so far
      obtained].

PMID- 15438832
TI  - [Oristidal in the treatment of ulcerous gastroduodenitis and gastroduodenal
      ulcers].

PMID- 15438833
TI  - [Clinical and electrocardiographical data on 152 cases of myocardial infarct].

PMID- 15438834
TI  - [Treatment of whooping cough with streptomycin and hyperconcentrated vaccine].

PMID- 15438835
TI  - [Pharmaco-biological research on a new type of hydrosoluble rutin].

PMID- 15438836
TI  - [Ankylosing spondylitis].

PMID- 15438837
TI  - [First aid in hemorrhage due to dicumarol].

PMID- 15438838
TI  - [Sulfonamides in the past, present and future].

PMID- 15438839
TI  - [Contribution of the Portuguese school to the development of neurosurgery].

PMID- 15438840
TI  - [Atomic radiations].

PMID- 15438841
TI  - [Origin and present development of stratigraphy; contribution of the Genoan and
      Italian school of radiology].

PMID- 15438842
TI  - [Stratigraphy in pulmonary tuberculosis].

PMID- 15438843
TI  - [Thoracic kymography].

PMID- 15438844
TI  - [Ultrasounds].

PMID- 15438845
TI  - [Ultrasounds in therapy].

PMID- 15438846
TI  - [Recent progress of cardiac and vascular surgery].

PMID- 15438847
TI  - [Surgery of the great vessels].

PMID- 15438848
TI  - [Surgery of the heart].

PMID- 15438849
TI  - [Surgery of the pericardium].

PMID- 15438850
TI  - [Clinical aspect and physiopathology of the tetralogy of Fallot; indications for
      surgery].

PMID- 15438851
TI  - [Clinical aspects of septal myocardial infarct].

PMID- 15438852
TI  - [Arteriovenous aneurysms of the brain].

PMID- 15438853
TI  - [Surgical treatment of mental psychosurgical) diseases].

PMID- 15438854
TI  - [Electroencephalography in neurosurgical diagnosis].

PMID- 15438855
TI  - [Transorbital prefrontal leucotomy in psychosurgery].

PMID- 15438856
TI  - [Physio mechanical principles, indications, late results of apical-axillary
      thoracoplasty].

PMID- 15438857
TI  - [Ten aphorisms on spontaneous hemostasis; its disorders and treatment].

PMID- 15438858
TI  - [Treatment of tuberculosis with thiosemicarbazones].

PMID- 15438859
TI  - [Results of treatment of pulmonary tuberculosis with conteben].

PMID- 15438860
TI  - [Antibiotics in human therapy, with particular reference to tuberculosis].

PMID- 15438861
TI  - [Angiocardiography; its value and limits].

PMID- 15438862
TI  - [Diapneumotherapy].

PMID- 15438863
TI  - [Vertigo; criteria for clinical and therapeutic evaluation].

PMID- 15438864
TI  - [Recent progress in the field of odontostomatology].

PMID- 15438865
TI  - [Precancerous lesions of the oral cavity; clinical and anatomopathological
      considerations].

PMID- 15438866
TI  - [Clinical observations on the use of trichloroethylene in stomatology].

PMID- 15438867
TI  - [New diagnostic methods in so-called focal infections of dental origin].

PMID- 15438868
TI  - [Surgery of congenital cyanosis].

PMID- 15438869
TI  - [Physiopathological data obtained with I131 in the study of cancer of the
      thyroid].

PMID- 15438870
TI  - [Amputation stumps, preparatory treatment and application of the prosthesis].

PMID- 15438871
TI  - [Study of twins in science].

PMID- 15438872
TI  - [Philosophy of art and exegesis of its manifestations].

PMID- 15438873
TI  - [Do narcoanalysis, psychoanalysis and projective methods of analysis represent an
      infringement of personal liberty?].

PMID- 15438874
TI  - [Euthanasia].

PMID- 15438875
TI  - [Important and urgent problems of aeronautic medicine].

PMID- 15438876
TI  - [Indications and contraindications in the air transportation of the sick or
      wounded].

PMID- 15438877
TI  - [Clinical diagnosis of congenital heart disease].

PMID- 15438878
TI  - [Ascoli treatment of malaria].

PMID- 15438879
TI  - [Television and surgery].

PMID- 15438880
TI  - [Acute leukemia in children; cytology, etiology and therapy].

PMID- 15438881
TI  - [Clinical variations of acute infantile leukemia].

PMID- 15438882
TI  - [Cytochemical criteria applied to the cytologic diagnosis of acute leukosis].

PMID- 15438883
TI  - [The term leukemia in pediatric hospital practice].

PMID- 15438884
TI  - [A case of chronic myeloid leukemia in an infant, treated with urethane].

PMID- 15438885
TI  - [Considerations on a case of leukemoid reaction in an infant].

PMID- 15438886
TI  - [Clinical contribution to the remission phase of acute leukemia].

PMID- 15438887
TI  - [The so-called rheumatoid form of acute leukemia of infancy].

PMID- 15438888
TI  - [A case of very acute leukemia with early mastoid localization].

PMID- 15438889
TI  - [First results of treatment with aminopterin of acute leukemia; preliminary
      communication].

PMID- 15438890
TI  - [Limits of the efficacy of PAS in primary pulmonary tuberculosis and indications
      for associated PAS-streptomycin treatment; research and considerations on 185
      cases].

PMID- 15438891
TI  - [Pathogenesis of the hemorrhagic syndromes].

PMID- 15438892
TI  - [An unusual disorder of bone growth: epiphyseal dysgenesis in athyreosis and
      hypothyreosis].

PMID- 15438894
TI  - [Case of grave congenital ichthyosis].

PMID- 15438893
TI  - [700 cases of death of infants of medico-legal interest].

PMID- 15438895
TI  - [Syndrome of striata dysgenesis with muscular dystrophy and choreiform dyskinesia
      of obscure etiology in an infant].

PMID- 15438896
TI  - [Remote neuromental prognosis of an 860 gr. premature infant, with some
      considerations on the mental prognosis of premature infants].

PMID- 15438897
TI  - [Evaluation of allergometric tuberculin data].

PMID- 15438898
TI  - A better rural transfusion program.

PMID- 15438899
TI  - Psychological medicine in a general medical setting.

PMID- 15438900
TI  - The 1949 cancer statistical study, Minnesota Department of Health.

PMID- 15438901
TI  - Infant methemoglobinemia in Minnesota due to nitrates in well water.

PMID- 15438902
TI  - Pituitary adrenocorticotropic hormone (ACTH) in asthma.

PMID- 15438903
TI  - Renal tumors.

PMID- 15438904
TI  - Medicine and its practitioners in Olmested County prior to 1900.

PMID- 15438905
TI  - Prophylaxis in allergic disease and management of the eczematoid dermatoses of
      infancy and childhood.

PMID- 15438906
TI  - Current trends in shock therapy.

PMID- 15438907
TI  - The crisis and our duty.

PMID- 15438908
TI  - Fifty-Year Club address.

PMID- 15438909
TI  - Retropubic prostatectomy.

PMID- 15438910
TI  - External injuries of the eye.

PMID- 15438911
TI  - Hematogenous osteomyelitis due to Escherichia coli.

PMID- 15438912
TI  - Pulmonary complications in heart disease.

PMID- 15438913
TI  - The hospital labor front is boiling.

PMID- 15438915
TI  - Small hospital features double corridor.

PMID- 15438914
TI  - Hospitals must fight union domination.

PMID- 15438916
TI  - Punch card accounting lightens the load of paper work.

PMID- 15438917
TI  - As the doctor sees hospital physician relationships.

PMID- 15438918
TI  - Peralta's plan of expansion meets changing concepts of hospital care.

PMID- 15438919
TI  - Medication cost study features disposable injection unit.

PMID- 15438920
TI  - Civilian defense is back in the hospital spotlight.

PMID- 15438921
TI  - They made hospital history: Ignaz Philipp Semmelweis.

PMID- 15438922
TI  - Cystoscopy rooms are designed for utility.

PMID- 15438923
TI  - Don't overlook the ambulance as a public relations tool.

PMID- 15438924
TI  - What should hospitals do about health insurance?

PMID- 15438925
TI  - HOSPITAL goes "on record" with its sales story.

PMID- 15438926
TI  - How one community reads its hospital house organ.

PMID- 15438927
TI  - The practical nurse is on her way to a place on the nursing team.

PMID- 15438928
TI  - FIRE safety measures include inspections and compliance with fire department
      recommendations.

PMID- 15438929
TI  - British administrators review their hospital system today.

PMID- 15438930
TI  - Thyroid patients get help from Grant Hospital's isotope laboratory.

PMID- 15438931
TI  - The future of pharmacy as a profession may lie in hospital and clinical practice.

PMID- 15438932
TI  - Effect of drugs on brain waves.

PMID- 15438933
TI  - Will china take a back seat?

PMID- 15438934
TI  - Bureau of Labor Statistics studies salaries of dietitians.

PMID- 15438935
TI  - Menus for October 1950.

PMID- 15438937
TI  - The laundry steps aside to make room for a new addition and ultimately for a new
      laundry.

PMID- 15438936
TI  - Functional engineering is as important as functional architecture.

PMID- 15438938
TI  - [Influence of Karl Jaspers on psychopathology].

PMID- 15438939
TI  - [The olivotegmental tract in man, with 2 cases of midbrain tractotomy].

PMID- 15438940
TI  - [Clinical aspect of so-called deeper reflexes and reflexogenic zones].

PMID- 15438941
TI  - [Psychic disorders in chronic mercurialism].

PMID- 15438942
TI  - [Spontaneous and intentional clonic spasms in two atypical forms of general
      paralysis].

PMID- 15438943
TI  - [Cytoarchitectonics of the centrum medianum thalami in man].

PMID- 15438944
TI  - [Huntington's chorea and paralysis agitans].

PMID- 15438945
TI  - Contributions to the clinical aspects and to the patho-anatomy of pachymeningitis
      spinalis externa.

PMID- 15438946
TI  - [Determination of pregnandiol with special reference to personal research on
      photometric determination of the curve, not previously known].

PMID- 15438947
TI  - [Sarcomatous degeneration of the mucosa of a fibrous polyp of the uterus;
      anatomopathological considerations].

PMID- 15438948
TI  - [Penicillin by intravaginal administration].

PMID- 15438949
TI  - [Research on the biochemical modifications of the blood in normal and tuberculous
      women during various phases of the menstrual cycle. IV. Clinical interpretations
      of results and conclusions].

PMID- 15438950
TI  - [Necessity of a psychological investigation in obstetrics and gynecology].

PMID- 15438951
TI  - [Hydrohematosalpinx due to absence of the pavilion and of the tubo-abdominal
      orifice, in torsion].

PMID- 15438952
TI  - [Topographic and morphologic modifications of the lower urinary tract and of the
      rectal ampulla in prolapse of the uterus].

PMID- 15438953
TI  - [Importance of the urinary bladder in menstrual function; urinary factors which
      regulate the menstrual flow and their use in therapy].

PMID- 15438954
TI  - [Influence of sex hormones on serum cholinesterase; experimental research].

PMID- 15438955
TI  - [Research on the biochemical modifications of the blood in normal and tuberculous
      women during various phases of the menstrual cycle. V. Therapeutic problem of
      tuberculosis in pregnant and non-pregnant women].

PMID- 15438956
TI  - [Results of treatment with synthetic antihistamines in some form of
      menometrorrhagia].

PMID- 15438957
TI  - [Problems of present treatment of diabetes].

PMID- 15438959
TI  - [Main symptom: external swelling of the neck].

PMID- 15438958
TI  - [Chemotherapy, with special reference to the sulfonamides].

PMID- 15438960
TI  - [A positive catalyzer of cell division].

PMID- 15438961
TI  - [Patent Botallo's duct with endarteritis lenta].

PMID- 15438962
TI  - [Endocarditic and hepatitic manifestations of nutritional dystrophy].

PMID- 15438963
TI  - [Clauden therapy of spontaneous pneumothorax].

PMID- 15438964
TI  - [Tuberculosis control in the Soviet-German Democratic Republic].

PMID- 15438965
TI  - [Suggestion concerning the introduction of a health card].

PMID- 15438966
TI  - [Kidney disease and blood pressure].

PMID- 15438967
TI  - [Fever therapy of chronic tetanus].

PMID- 15438968
TI  - [Superficial hypnosis].

PMID- 15438969
TI  - [Operative utilization of the retained muscles in poliomyelitis].

PMID- 15438970
TI  - [Genesis and surgical therapy of essential and released high blood pressure].

PMID- 15438971
TI  - [Can Dupuytren's contracture be treated successfully?].

PMID- 15438972
TI  - [Myogenic headache].

PMID- 15438973
TI  - [Our experiences with intravenous amino acid infusions].

PMID- 15438974
TI  - [Biological and pharmacological principles of penicillin side-effects in their
      importance in theory and practice].

PMID- 15438975
TI  - [Necrotizing ulcerous terminal ileitis and esophagitis following burns].

PMID- 15438976
TI  - [Is there the danger of a Sanarelli-Shwartzman reaction in the use of pyrifer?].

PMID- 15438977
TI  - [Therapeutic effect of small doses of pyrifer in ophthalmology].

PMID- 15438978
TI  - [Experiences with hirudoid].

PMID- 15438979
TI  - [Biomotor in cardiac and circulatory practice].

PMID- 15438980
TI  - [Newly recognized effect of a high polymer accompanying carbohydrate in infant
      feeding].

PMID- 15438981
TI  - [Reglimentation or hygiene].

PMID- 15438982
TI  - [Clinical instruction].

PMID- 15438983
TI  - [Physicians in Berlin since 1945].

PMID- 15438984
TI  - [Significance of carotenoid deficiency in the new goiter epidemic].

PMID- 15438985
TI  - [Observations on different skin reactions in pregnancy following intracutaneous
      injection of androgens, and the relation to the sex of the fetus].

PMID- 15438986
TI  - [Vitamin E and blood sugar].

PMID- 15438987
TI  - [Constitutional changes in chronic tuberculous meningitis].

PMID- 15438988
TI  - [Glossitis rhombica mediana of Brocq-Pautrier].

PMID- 15438989
TI  - [Trace elements].

PMID- 15438990
TI  - [New remedies in treatment of leukorrhea].

PMID- 15438991
TI  - [Serological diagnosis of virus influenza with aid of Hirst's agglutination
      test].

PMID- 15438993
TI  - [Treatment of carbon monoxide poisoning].

PMID- 15438992
TI  - [Treatment of sulfonamide nephrosis].

PMID- 15438994
TI  - [Problem of doctors in the Eastern zone and in the Eastern Sector of Berlin].

PMID- 15438996
TI  - [In memoriam Hans Curschmann].

PMID- 15438995
TI  - [Max Joseph Oertel, a pioneer in laryngology and originator of the terrain cure].

PMID- 15438997
TI  - [Aphorisms on endocarditis lenta (slow, sub-acute)].

PMID- 15438998
TI  - [Scarlet fever in general practice].

PMID- 15438999
TI  - [Comparative studies of the precordial electrocardiogram with various distant
      electrodes (chest-foot and chest-back leads, and leads with Wilson's single
      electrode)].

PMID- 15439000
TI  - [Significance of carotenoid deficiency in the new goiter epidemic].

PMID- 15439001
TI  - [Efficacy of human milk].

PMID- 15439002
TI  - [Use of chloromycetin in treatment of a typhoid carrier].

PMID- 15439003
TI  - [Poisoning by the new insecticide E650f and related substances].

PMID- 15439004
TI  - [Harry Marcus on his 70th birthday].

PMID- 15439006
TI  - [New aspects of etiology and treatment in peptic ulcer].

PMID- 15439005
TI  - [Peristalsis and tonus of the stomach].

PMID- 15439007
TI  - [Nutritional dystrophy and stomach ulcer].

PMID- 15439008
TI  - [Cascade stomach].

PMID- 15439009
TI  - [Problems of present treatment of diabetes].

PMID- 15439010
TI  - [Aphorisms on endocarditis lenta (slow, sub-acute)].

PMID- 15439011
TI  - [Internal use of formaldehyde in stomach pathology].

PMID- 15439012
TI  - [Experiences with hepsan, a new methionine-choline preparation, in treatment of
      acute epidemic hepatitis].

PMID- 15439013
TI  - [Congenital malformations of the heart and large vessels; a survey of modern
      diagnosis and therapy].

PMID- 15439014
TI  - [Allergy in childhood].

PMID- 15439015
TI  - [Surgical therapy of jaundice].

PMID- 15439016
TI  - [Phobogenic enteralgia (stomach ache due to anxiety)].

PMID- 15439017
TI  - [Treatment of congenital dislocation of the hip in infancy].

PMID- 15439018
TI  - [Fatal meningitis following epidemic parotitis].

PMID- 15439019
TI  - [Clinical aspect and differential diagnosis of serous meningitis].

PMID- 15439020
TI  - [New aspects of etiology and treatment of peptic ulcer].

PMID- 15439021
TI  - [Clinical test of an infant pabulum favorable to production of the bifidus
      bacillus].

PMID- 15439022
TI  - [Modern British anesthesia technics].

PMID- 15439023
TI  - [Use of invocan forte in infectious diseases].

PMID- 15439024
TI  - [Treatment of oxyuriasis with triphenylmethane derivatives].

PMID- 15439025
TI  - [In memoriam Franz Volhard].

PMID- 15439026
TI  - [Termination of pregnancy; socio-legal aspects of induced abortion].

PMID- 15439027
TI  - [Medical indications for termination of pregnancy].

PMID- 15439028
TI  - [Abortion and criminal intent].

PMID- 15439029
TI  - [Congenital malformations of the heart and great vessels; a survey of modern
      diagnosis and therapy].

PMID- 15439030
TI  - [Main symptom: tachycardia].

PMID- 15439031
TI  - [Basic principles in the use of retarded-action penicillins].

PMID- 15439032
TI  - [Clinical and epidemiologic experiences with field fever].

PMID- 15439033
TI  - [Leptospirotic meningitis; clinical aspect of acute aseptic meningitis of
      childhood].

PMID- 15439034
TI  - [Recurrence of parrot fever (psittacosis)].

PMID- 15439035
TI  - [The physician in an atomic war].

PMID- 15439036
TI  - [Colpan therapy of leukorrhea].

PMID- 15439037
TI  - [Further investigations on the effect of new German retarded-action penicillins
      upon the blood picture].

PMID- 15439038
TI  - [Voluntary participation of health workers in the activities of the Peoples'
      Front].

PMID- 15439039
TI  - [A short review of the work of our health service in 1949 and programs for 1950].

PMID- 15439040
TI  - [The problems of labor management].

PMID- 15439041
TI  - [Conditions and problems of medical and pharmaceutical periodicals in
      Yugoslavia].

PMID- 15439042
TI  - [The Yugoslavian pharmacopeia].

PMID- 15439043
TI  - [How to write critical accounts of scientific works].

PMID- 15439044
TI  - [Training of doctors (its development and its dependence on social conditions)].

PMID- 15439045
TI  - [Financing and financial activities of health institutions].

PMID- 15439046
TI  - [Instructions concerning the inventory of hospital beds and the working clothes
      of the personnel in health institutions].

PMID- 15439047
TI  - [Foundation, organization and administration of a hospital].

PMID- 15439048
TI  - [Foundation, organization and administration of a children's camp].

PMID- 15439049
TI  - [Foundation, organization and administration of homes for mothers].

PMID- 15439050
TI  - INDUSTRIAL organization as a creative social institution.

PMID- 15439051
TI  - Life and work of Oliver Heaviside (May 18, 1850-February 3, 1925).

PMID- 15439052
TI  - New cytotoxic agents with tumour-inhibitory activity.

PMID- 15439053
TI  - Early days of genetics in Britain.

PMID- 15439054
TI  - Comparison of the east Anglian and continental Pleistocene.

PMID- 15439055
TI  - Vibriostatic activity in certain series of pteridines.

PMID- 15439056
TI  - MIDLAND Coke Research Station.

PMID- 15439057
TI  - SOUTH-EASTERN Union of Scientific Societies; Annual Congress.

PMID- 15439059
TI  - EARTHQUAKES during January-March.

PMID- 15439058
TI  - Standardization of units of measurement in civil aviation.

PMID- 15439060
TI  - Preparation of specimens for the electron microscope.

PMID- 15439061
TI  - 2-Hydroxypyrimidine.

PMID- 15439062
TI  - 4:5:6:7-Tetrahydroindan-1-one.

PMID- 15439063
TI  - Mean restoring forces of hydride di-atoms and their positive ions.

PMID- 15439064
TI  - Hydrolysis of osmium compounds.

PMID- 15439065
TI  - Constitution of ferri-phenol complex in solution.

PMID- 15439066
TI  - An auroral spectrogram obtained at Oslo on February 23.

PMID- 15439067
TI  - Spectrum of a meteor train.

PMID- 15439068
TI  - Nuclear resonance and magnetic field changes of 1 in 106.

PMID- 15439069
TI  - Disintegration of neon by fast neutrons.

PMID- 15439070
TI  - A test of the interpretation of X-ray patterns of micelles.

PMID- 15439072
TI  - Sudden commencements in geomagnetism.

PMID- 15439071
TI  - Gamma-rays from thulium-170.

PMID- 15439073
TI  - Masses of fundamental particles.

PMID- 15439074
TI  - Mechanism of the Geiger discharge.

PMID- 15439075
TI  - The scintillation of stars.

PMID- 15439076
TI  - Magneto-hydrodynamic waves in a plasma.

PMID- 15439078
TI  - The karyolytic factor in the serum of rats injected with colchicine.

PMID- 15439077
TI  - Magneto-hydrodynamic waves in a compressible fluid conductor.

PMID- 15439079
TI  - c-Mitotic action of some simple gases.

PMID- 15439080
TI  - Purification of a precursor of nicotinic acid from wheat bran.

PMID- 15439081
TI  - A technique for the selection of red clover seedlings resistant to the clover rot
      fungus, Sclerotinia trifoliorum Eriksson.

PMID- 15439083
TI  - Aphid migration and the spread of plant viruses.

PMID- 15439082
TI  - Protozoan hyperparasitism of Heterakis gallinae.

PMID- 15439084
TI  - Recent Irish records of rare fish.

PMID- 15439085
TI  - A little-known tyroglyphoid mite, Histiostoma polypori (Oud.) and its association
      with the earwig, Forficula auricularia Linn.

PMID- 15439086
TI  - South African stone age terminology.

PMID- 15439087
TI  - Famous experimental apparatus in the Cavendish Laboratory, Cambridge.

PMID- 15439088
TI  - The neurogenic heart and ether anesthesia.

PMID- 15439090
TI  - Nature of nucleotoxic substances.

PMID- 15439089
TI  - The scintillation counter.

PMID- 15439091
TI  - Shell disease in re-laid French oysters.

PMID- 15439093
TI  - TURF and greenkeeping; St. Ives Research Station.

PMID- 15439092
TI  - Gaussian approximations to wave functions.

PMID- 15439094
TI  - New techniques in autoradiography.

PMID- 15439095
TI  - Spectroscopy of cells: the use of a reflecting microscope and spectrographic
      recording.

PMID- 15439096
TI  - Helium II transfer on metal surfaces.

PMID- 15439097
TI  - The D-D reaction as a standard neutron source.

PMID- 15439098
TI  - Mechanism of ignition by local sources of heat.

PMID- 15439099
TI  - Low-frequency dielectric absorption in organic long chain compounds due to the
      presence of traces of alcohol impurities.

PMID- 15439100
TI  - Fundamental lengths and masses of fundamental particles.

PMID- 15439101
TI  - Magnetism and the rotation of celestial bodies.

PMID- 15439102
TI  - Origin of sunspots.

PMID- 15439103
TI  - Biological assay of small quantities of desoxycorticosterone acetate.

PMID- 15439104
TI  - Direct oxidation of glucose-6-phosphate by animal tissues.

PMID- 15439105
TI  - Birefringence of amylose and amylopectin in whole structural starches.

PMID- 15439106
TI  - Quantitative estimation of stomatal starch.

PMID- 15439107
TI  - High light intensities for experiments in crop physiology.

PMID- 15439108
TI  - Occurrences in normal human sera of 'incomplete' forms of 'cold' auto-antibodies.

PMID- 15439109
TI  - Heteropycnosis in human chromosomes.

PMID- 15439110
TI  - Anomalous results of mothproofing tests.

PMID- 15439111
TI  - Reciprocal translocations in Pisum.

PMID- 15439112
TI  - An Archiannelid from South Africa.

PMID- 15439113
TI  - The Bell Telephone Laboratories.

PMID- 15439114
TI  - Thomas Wright's "original theory" of the Milky Way.

PMID- 15439115
TI  - Dunlop Research Centre, Birmingham.

PMID- 15439116
TI  - Sir James Henderson.

PMID- 15439117
TI  - A new approach to the synthesis of ethylenic compounds.

PMID- 15439118
TI  - Molecular models.

PMID- 15439119
TI  - The gestural origin of language; evidence from six 'unrelated' languages.

PMID- 15439120
TI  - Developments in the heat treatment of milk.

PMID- 15439121
TI  - American education.

PMID- 15439122
TI  - Antibacterial and antifungal activity of benztropolone.

PMID- 15439123
TI  - A novel method of using ion-exchange, resins.

PMID- 15439124
TI  - Separation of carboxylate ions on the paper chromatogram.

PMID- 15439125
TI  - Hydrolysis of laminarin by wheat beta-amylase.

PMID- 15439126
TI  - Separation of noradrenaline and adrenalin.

PMID- 15439127
TI  - Positive bromine ions.

PMID- 15439128
TI  - Reaction of methylcycloalkyl hydroperoxides with ferrous sulphate.

PMID- 15439129
TI  - Anomalous thermal expansion of the short intermolecular bond in para-nitro
      aniline.

PMID- 15439130
TI  - A characteristic example of re-trapping in phosphorescence.

PMID- 15439131
TI  - Exceptional performance of a nuclear ignition Otto-cycle engine using n-pentane
      as fuel.

PMID- 15439132
TI  - The reticulospinal apparatus and rigidity.

PMID- 15439133
TI  - Insecticidal action of radioactive bis-(bis-dimethylamino)-phosphonous anhydride.

PMID- 15439134
TI  - Effect of leaf roll virus on the amino-acid composition of potato tubers.

PMID- 15439135
TI  - Variations in Aulacorthum solani Kalt.

PMID- 15439136
TI  - Longevity in the grey seal.

PMID- 15439137
TI  - Influence of pregnancy and social facilitation on the behaviour of the grazing
      sheep.

PMID- 15439138
TI  - Life-history of the European earwig, Forficula auricularia.

PMID- 15439139
TI  - Phalaropes in central Borneo.

PMID- 15439140
TI  - South Pacific Chlorophyceae.

PMID- 15439141
TI  - Effect of sowing time and photoperiods in Sorghum roxburghii var. hians, Stapf.
      (Jowar).

PMID- 15439142
TI  - Gamete behaviour in Chlamydomonas.

PMID- 15439143
TI  - Pectic enzymes of the fungus Byssochlamys fulva.

PMID- 15439144
TI  - Two phases of the water metabolism in newly born rats.

PMID- 15439145
TI  - Nature of the vitamin B1-sparing action of fat.

PMID- 15439146
TI  - Vitamin B12 as an anti-anaphylactic.

PMID- 15439147
TI  - Effect of rain in calming the sea.

PMID- 15439148
TI  - United States Science Offices abroad.

PMID- 15439149
TI  - Physical chemistry of drug action.

PMID- 15439150
TI  - Operational analysis and the nature of some physical concepts.

PMID- 15439151
TI  - Antibiotics in the soil.

PMID- 15439152
TI  - Effects of radio gyrointeraction and their interpretation.

PMID- 15439153
TI  - A microscopic electrophoresis cell.

PMID- 15439154
TI  - Nomenclature of the steroidal sapogenins.

PMID- 15439155
TI  - Mechanism of the rearrangement of quinamine to iso quinamine.

PMID- 15439156
TI  - Synthesis of ergothioneine.

PMID- 15439157
TI  - Stereochemical course of reactions at steroid C17.

PMID- 15439158
TI  - Structure of trans-potassium dioxalato-diaquo-chromiate.

PMID- 15439159
TI  - Reactions of 9-anthraldehyde in sunlight.

PMID- 15439160
TI  - Thermal decomposition of potassium perchlorate.

PMID- 15439161
TI  - Are tyrosinase and thiol groups present in skin epithelium?

PMID- 15439163
TI  - Ultra-violet radiation in the sea.

PMID- 15439162
TI  - Low-cost air transport of radioactive substances to South Africa.

PMID- 15439164
TI  - Isotopic composition of the oxygen in silicate rocks.

PMID- 15439165
TI  - Applications of polarimetry to infra-red and micro-wave spectroscopy.

PMID- 15439166
TI  - Ultrasonic absorption in some mixtures of unassociated and an associated liquid.

PMID- 15439167
TI  - Anharmonicity of the lattice oscillations in the alkali halide crystals.

PMID- 15439168
TI  - Modification of a fingerprint by a skin graft.

PMID- 15439169
TI  - 'Weber's glands' and respiration in woodlice.

PMID- 15439170
TI  - Identity of a muscle-inhibiting flavone in lucerne.

PMID- 15439171
TI  - Statistical planning in experiments on the isolated rat uterus.

PMID- 15439172
TI  - The soil-plate method for isolation of fungi from soil.

PMID- 15439173
TI  - A percolating respirometer.

PMID- 15439175
TI  - Colour systems and atlases.

PMID- 15439174
TI  - Tobacco mosaic virus crystals and three-dimensional microscopic vision.

PMID- 15439176
TI  - CHEMICAL research laboratory, Teddington.

PMID- 15439177
TI  - Isoelectronic reactions in conjugated systems.

PMID- 15439178
TI  - Antibacterial activity of a substance present in ticks (Ixodoidea) of Texas.

PMID- 15439179
TI  - International Convention on Ultrasonics.

PMID- 15439180
TI  - Angular correlation between alpha-particles and alpha-rays in the reaction F19
      (rho, alpha gamma)O 16.

PMID- 15439181
TI  - Chemical effects of ionizing radiation in some gels.

PMID- 15439182
TI  - A correlation of restoring coefficients in molecular potential functions and bond
      orders between the different atoms in polyatomic molecules.

PMID- 15439183
TI  - X-ray analysis of the swelling of wood pulp in sodium hydroxide solution.

PMID- 15439184
TI  - Age of extremely ancient pegmatites from south-eastern Manitoba.

PMID- 15439185
TI  - Use of plastics in the Fresnel rhomb.

PMID- 15439186
TI  - Absorption spectrum of indium vapour in the Schumann region.

PMID- 15439187
TI  - The scintillation of stars.

PMID- 15439188
TI  - Marching in locust hoppers of the solitary phase.

PMID- 15439189
TI  - Effect of carbon/nitrogen ratio upon the formation of nitrate and ammonia from
      amino-acids in soil.

PMID- 15439190
TI  - Photoperiodic induction in jute and a great acceleration of vegetative growth in
      Corchorus capsularis.

PMID- 15439192
TI  - Odour trails of Acanthomyops fuliginosus.

PMID- 15439191
TI  - Habits of the marine tardigrade, Echiniscoides sigismundi.

PMID- 15439193
TI  - Feeding mechanisms in anuran tadpoles.

PMID- 15439194
TI  - Exoerythrocytic schizogony in bat malaria.

PMID- 15439195
TI  - Failure of antibiotics in experimental rabies.

PMID- 15439196
TI  - Hydrolysis of organic nitrates.

PMID- 15439197
TI  - Role of oxygen in the photolysis of iodides.

PMID- 15439198
TI  - Monoclinic thorium silicate.

PMID- 15439199
TI  - The sulphatase of 'clarase': inhibition, inactivation and purification.

PMID- 15439200
TI  - Reciprocal detoxifying effects of 'benadryl' and 'aminopterin'.

PMID- 15439201
TI  - South African fossil hominoids.

PMID- 15439202
TI  - A Joule Museum at Manchester.

PMID- 15439203
TI  - Phosphorus in peripheral nerve.

PMID- 15439204
TI  - Atomic definition of primary standards.

PMID- 15439205
TI  - Rice production and utilization.

PMID- 15439206
TI  - Physico-chemical properties of nucleic acids.

PMID- 15439207
TI  - British leather manufacturers' research association.

PMID- 15439208
TI  - [Dr A J Bull].

PMID- 15439209
TI  - Configuration of carbohydrates, hydroxy-acids and amino-acids; stereochemical
      standards of configuration.

PMID- 15439210
TI  - Configurations of amino-compounds and the steric course of deamination.

PMID- 15439211
TI  - Biology of adult mosquitoes in eastern Colombia.

PMID- 15439212
TI  - The health of England and Wales.

PMID- 15439213
TI  - Mechanism of absorption of inorganic phosphate from blood by tissue cells.

PMID- 15439214
TI  - Tracer experiments in Mammals with dicumarol labeled with carbon-14.

PMID- 15439215
TI  - Lipids of squid nerve.

PMID- 15439216
TI  - Composition of human sero-mucoprotein.

PMID- 15439217
TI  - A sulphated mucopolysaccharide in human dentine.

PMID- 15439218
TI  - Inorganic pyrophosphate in insect tissue.

PMID- 15439219
TI  - A simple gasometric method for the analysis of the fermentation-inhibiting
      properties of antimicrobic agents.

PMID- 15439220
TI  - Penetration of benzpyrene through the intact skin of new-born mice.

PMID- 15439221
TI  - Oriented overgrowth of alkali halides on metals.

PMID- 15439223
TI  - Oscillator strength of the Na2 'xi-'xi transition.

PMID- 15439222
TI  - An infrared band-system of calcium oxide.

PMID- 15439224
TI  - New general methods for the synthesis of fluoroiodides and fluoroacids.

PMID- 15439225
TI  - Electron affinities of some aromatic molecules.

PMID- 15439226
TI  - Chain configurations in natured and denatured insulin: evidence from infrared
      spectra.

PMID- 15439227
TI  - A subsidiary shell pigment of Haliotis cracherodii leach.

PMID- 15439228
TI  - Chromatographic analysis of eucalypt kinos.

PMID- 15439229
TI  - Chemical delignification of flax straw and other cellulosic materials.

PMID- 15439230
TI  - Induced vitamin-requiring mutants of Chlamydomonas.

PMID- 15439231
TI  - Mango: its allopolyploid nature.

PMID- 15439232
TI  - The alleged membrane potential produced by diffusion in nerve and muscle fibers.

PMID- 15439233
TI  - A recent deposit of bird bones in the Falkland Islands.

PMID- 15439234
TI  - New photosensitive pigments from the tench retina.

PMID- 15439235
TI  - Occurrence of a phosphoric ester in certain bacteria: its relation to gram
      staining and penicillin sensitivity.

PMID- 15439236
TI  - Long Ashton Research Station.

PMID- 15439237
TI  - Electronic instruments and devices.

PMID- 15439238
TI  - Universities and management.

PMID- 15439239
TI  - Trifluoromethyl derivatives of phosphorus, arsenic and sulphur.

PMID- 15439240
TI  - Synthesis of a benzene ring with a ten-membered para-bridge.

PMID- 15439241
TI  - Quantitative paper chromatography on mixed solutions of nickel and cobalt, and
      determination of both elements.

PMID- 15439242
TI  - A new reaction of ethylenic double bonds.

PMID- 15439243
TI  - Structure of cyclo-octatetraene.

PMID- 15439244
TI  - Heterochromatin.

PMID- 15439245
TI  - Induction of mutation by high-energy x-radiation produced by a 23-MeV. betatron.

PMID- 15439247
TI  - A simple technique for the study of vascular pattern.

PMID- 15439246
TI  - Identification of transplanted tissues in chick embryos by marking with
      phosphorus-32.

PMID- 15439248
TI  - Cause of the absorption of water by submerged shoots.

PMID- 15439249
TI  - Hypersensitivity and tumour development in potato tubers in response to
      infections with Phytophthora infestans.

PMID- 15439250
TI  - Sharp eyespot as a severe disease of oats.

PMID- 15439252
TI  - Principle of an ion source for intense beams.

PMID- 15439251
TI  - Humidity and temperature in grass microclimates with reference to insolation.

PMID- 15439253
TI  - Extraction of the electron beam from a 30-MeV. synchrotron.

PMID- 15439254
TI  - Production of beryllium-7 by proton bombardment of carbon.

PMID- 15439255
TI  - Stress-birefringence in polystyrene.

PMID- 15439256
TI  - Interlamellar adsorption of protein monolayers on pure montmorillonoid clays.

PMID- 15439257
TI  - Gabor diffraction microscopy: the hologram as a generalized zone-plate.

PMID- 15439258
TI  - Occurrence of 5-methylcytosine in nucleic acids.

PMID- 15439259
TI  - "Polyploidy in rabbits".

PMID- 15439260
TI  - Nitrification of amino-acids.

PMID- 15439261
TI  - Genetical structure of populations.

PMID- 15439262
TI  - Stellar magnetic fields.

PMID- 15439263
TI  - An approach to x-ray microscopy.

PMID- 15439264
TI  - Admiral Sir A. Mostyn Field.

PMID- 15439265
TI  - R V Norris.

PMID- 15439266
TI  - DR. Otto A Beeck.

PMID- 15439267
TI  - Mechanism of the beta-amylolysis of amylose.

PMID- 15439268
TI  - Electromagneto-ionic waves.

PMID- 15439269
TI  - British Cast Iron Research Association.

PMID- 15439270
TI  - Musk and the musk deer.

PMID- 15439271
TI  - BRITISH scientific instruments at the Canadian International Trade Fair, Toronto.

PMID- 15439272
TI  - Soluble carbohydrates of fruit plants.

PMID- 15439274
TI  - Sorption of water vapour by tobacco mosaic virus.

PMID- 15439273
TI  - Factors concerned with the oxidation of reduced coenzymes, and reduction of
      cytochrome e in pea seedlings.

PMID- 15439275
TI  - Polyvinylphosphate contractile systems.

PMID- 15439276
TI  - Salicylhydroxamic acid as an antitubercular agent.

PMID- 15439277
TI  - Metaphosphate in the excreta of the wax moth, Galleria mellonella.

PMID- 15439278
TI  - Identification of p-cresol as a toxin in oestrogen concentrates from sheep urine.

PMID- 15439280
TI  - Vitamin B12 assay in body fluids.

PMID- 15439279
TI  - Narcotics and the phosphates of brain.

PMID- 15439281
TI  - Conversion of hydrastine into berberine, and an instance of the asymmetrical
      quaternization of a tertiary base.

PMID- 15439282
TI  - Fluorescence of amino-acids, peptides and amines on filter paper.

PMID- 15439283
TI  - A reversed-phase partition chromatogram using chlorinated rubber.

PMID- 15439284
TI  - Treatment of paper for chromatography of some colloidal electrolytes.

PMID- 15439285
TI  - Colorimetric estimation of silver.

PMID- 15439286
TI  - Evaporation and mobility of naphthalene molecules.

PMID- 15439287
TI  - Size-frequency distributions.

PMID- 15439288
TI  - Runs up and down on a lattice.

PMID- 15439289
TI  - Mineralogical composition of quaternary Swedish clays.

PMID- 15439290
TI  - Earlier records of Elminius modestus Darwin in British waters.

PMID- 15439291
TI  - Extension and radial growth in trees.

PMID- 15439292
TI  - Synthesis of peptides in enzymic reactions involving glutathione.

PMID- 15439293
TI  - AGRICULTURAL genetics; conference at Rieti.

PMID- 15439294
TI  - Dr. Fabius Gross.

PMID- 15439295
TI  - DR. J. R. Ashworth.

PMID- 15439296
TI  - Mr. Thomas Lewis.

PMID- 15439297
TI  - Nature and relationships of the specific products of the human blood group and
      secretor genes.

PMID- 15439298
TI  - Sonic disintegration of isolated liver mitochondria.

PMID- 15439299
TI  - Modification of an antitubercular molecule.

PMID- 15439300
TI  - New simplified electron microscopes.

PMID- 15439301
TI  - Demonstrability of the photochemical formation of biradicals by magnetic methods.

PMID- 15439302
TI  - Nickel content of deep-sea deposits.

PMID- 15439303
TI  - Titrimetric determination of nitrates with an equivalent ratio of 1:8.

PMID- 15439304
TI  - Production of staphylocoagulase in a chemically defined medium.

PMID- 15439305
TI  - A cephalinase in nervous tissue.

PMID- 15439306
TI  - Effects of 'aminopterin' on the male sex organs of the guinea pig.

PMID- 15439307
TI  - Distribution of Chthamalus stellatus on the shores of north-east Ireland.

PMID- 15439308
TI  - Breeding and distribution of Chthamalus stellatus.

PMID- 15439309
TI  - The medusa Craspedacusta in Australia.

PMID- 15439310
TI  - Birefringence of amoebae.

PMID- 15439311
TI  - Preparation of standardized actinomycete colonies.

PMID- 15439312
TI  - Application of the Kozeny equation to consolidated porous media.

PMID- 15439313
TI  - A modification to Gabor's proposed diffraction microscope.

PMID- 15439314
TI  - Geometrical optics of ionospheric propagation.

PMID- 15439315
TI  - Large-scale sporadic movements of the E-layer of the ionosphere.

PMID- 15439316
TI  - Arc spectrum of gallium: new absorption lines in the Schumann region.

PMID- 15439317
TI  - Lead absorption of cosmic rays at different altitudes near magnetic latitude 22
      degrees N.

PMID- 15439318
TI  - Statistical analysis of results for successive tests on the same organism.

PMID- 15439319
TI  - Functional disturbances encountered in gynecic practice.

PMID- 15439321
TI  - The dentists' viewpoint.

PMID- 15439320
TI  - Fractures treated conservatively.

PMID- 15439322
TI  - Lumbar sympathectomy; report of fifty-five cases from Kansas City General
      Hospital.

PMID- 15439323
TI  - A preliminary report on the use of terramycin in pneumonia.

PMID- 15439324
TI  - [Effect of beryllium and its compounds upon humans].

PMID- 15439325
TI  - [Survey of treatment of angioma in the radiotherapeutic clinic of the Academic
      Hospital of Leiden, January 1946 to May 1949 (308 cases)].

PMID- 15439326
TI  - [Scrub Typhus].

PMID- 15439327
TI  - [Latent tetany with normal blood calcium as cause of autonomic disorders].

PMID- 15439328
TI  - [Manifestations of hypersensitivity following use of diparcol].

PMID- 15439329
TI  - [Operation on a 101 year old man for perforated appendix].

PMID- 15439330
TI  - [Artificial respiration].

PMID- 15439331
TI  - [Donors of the blood transfusion service].

PMID- 15439332
TI  - [F. G. M. Haase fifty years a physician].

PMID- 15439333
TI  - [Incidence of notifiable communicable disease in the Netherlands, week of 23-29
      April 1950].

PMID- 15439334
TI  - [Baker's eczema].

PMID- 15439335
TI  - [Chronic circumscribed balanitis with plasma cell infiltration].

PMID- 15439336
TI  - [Effect of sebum on the neutralization of alcali].

PMID- 15439337
TI  - [Determination of sex hormones in the urine in acne vulgaris].

PMID- 15439338
TI  - [Vitamin D intoxication].

PMID- 15439339
TI  - [Hydrocephalus].

PMID- 15439340
TI  - [Unusual cases of esophageal burns].

PMID- 15439341
TI  - [Maternal mortality in the gynecological clinic of the University of Amsterdam,
      1939-49].

PMID- 15439342
TI  - [Diagnosing the irritable bowel syndrome].

PMID- 15439343
TI  - [Toxicity of beverages containing caffeine].

PMID- 15439344
TI  - [Exotic plasmodia in the Netherlands; an appeal for cooperation among all
      Netherlands physicians].

PMID- 15439345
TI  - [Incidence of notifiable communicable disease in the Netherlands, week of 7-13
      May 50].

PMID- 15439347
TI  - [Racemose angioma of the cervical spinal cord].

PMID- 15439346
TI  - [Treatment of metastatic thyroid adenoma with radioactive iodine].

PMID- 15439348
TI  - [Color photography in the hospital].

PMID- 15439349
TI  - [Treatment of facial paralysis with fascioplasty].

PMID- 15439350
TI  - [Registration of blood oxygen during operation].

PMID- 15439351
TI  - [Disadvantages of antibiotics].

PMID- 15439352
TI  - [Combination of peridural anesthesia and narcosis].

PMID- 15439354
TI  - [Infection by Salmonella saintpaul in connection with salmonellosis in ducks].

PMID- 15439353
TI  - [Plasmocytoma].

PMID- 15439355
TI  - [Treatment of acute leukemia].

PMID- 15439356
TI  - [Ovarial hemorrhage].

PMID- 15439357
TI  - [Identification of tumor cells with May-Grunwald-Giemsa stained smears].

PMID- 15439359
TI  - [Functional cardiac disorder during and following recovery from postscarlatinal
      myocarditis].

PMID- 15439358
TI  - [Experience with electroencephalography in psychiatric and neurologic clinic].

PMID- 15439360
TI  - [Pathogenesis and pathological anatomy of congenital cardiovascular diseases].

PMID- 15439361
TI  - [Brainstem tumor treated with ventricular puncture and roentgen radiation].

PMID- 15439362
TI  - [Optic neuritis; sudden improvement following encephalography].

PMID- 15439363
TI  - [Surgical therapy of saccular aneurysm of the cerebral artery].

PMID- 15439365
TI  - [Besnier-Boeck disease].

PMID- 15439364
TI  - [Electrocardiography of heightened excitability of the carotid sinus reflex].

PMID- 15439366
TI  - [Research on the rhesus factor in the gynecological clinic of the University of
      Utrecht 1 Oct. 48 to 31 Dec. 49].

PMID- 15439367
TI  - [Macrodex (hydrolyzed dextran), a substitute for blood and plasma in the
      treatment of shock].

PMID- 15439368
TI  - [Psychological aspect of hospital care of various groups of patients].

PMID- 15439369
TI  - [Local and general anesthesia].

PMID- 15439370
TI  - [Werlhof's disease and pregnancy].

PMID- 15439371
TI  - [Favorable results in riboflavin therapy of porphyria].

PMID- 15439372
TI  - [Antabuse (refusal) out-patient therapy of chronic alcoholism].

PMID- 15439373
TI  - [Hypereosinophilia].

PMID- 15439374
TI  - [A new symptom of intervertebral disk hernia].

PMID- 15439375
TI  - [Diffractometric determination of diameter, volume, surface area and thickness of
      erythrocytes].

PMID- 15439376
TI  - [A small epidemic of psittacosis transmitted by a parakeet].

PMID- 15439377
TI  - [Cytologic diagnosis of pulmonary and uterine cancer].

PMID- 15439378
TI  - [Angioma of the muscle].

PMID- 15439379
TI  - [Psychosomatic treatment of bronchial asthma by the general practitioner].

PMID- 15439380
TI  - [Influenza-B in the Netherlands during the spring of 1950].

PMID- 15439381
TI  - [In memoriam Dr. R. J. Th. Meurer].

PMID- 15439382
TI  - [Tuberculosis of the skin].

PMID- 15439384
TI  - [Weber-Christian's disease, a form of spontaneous panniculitis].

PMID- 15439383
TI  - [Trepanomatosis].

PMID- 15439385
TI  - [Ultrasonic waves and their medical use].

PMID- 15439386
TI  - [Investigations of a circulating anticoagulant in hemophilia].

PMID- 15439387
TI  - [Effect of revaccination on the formation of antibodies (antihemagglutinins) in
      animals].

PMID- 15439388
TI  - [Generalized arteritis following use of methylthiouracil].

PMID- 15439389
TI  - [Effect of erythrodermia upon the organism].

PMID- 15439390
TI  - [Trichophytosis faviforme album].

PMID- 15439391
TI  - [Penicillin preparations for retarded action].

PMID- 15439392
TI  - [Periarteritis nodosa cutaneous].

PMID- 15439394
TI  - [Chronic and progressive granulomatosis disciformis].

PMID- 15439393
TI  - [Treatment of tuberculosis of the skin with sterols].

PMID- 15439395
TI  - [Xanthelasmatosis].

PMID- 15439396
TI  - [General observations on the nature of arthritis deformans].

PMID- 15439397
TI  - [Brachialgia and lumbalgia].

PMID- 15439398
TI  - [Spondylosis ankylopoetica].

PMID- 15439399
TI  - [Pathology of arthritis deformans].

PMID- 15439400
TI  - [Intracranial hypotension].

PMID- 15439401
TI  - [Acute hemolytic anemia with severe uremia following treatment with irgafen].

PMID- 15439402
TI  - [Erythema exsudativum multiforme].

PMID- 15439403
TI  - [Significance of erythema exsudativum multiforme in internal medicine].

PMID- 15439404
TI  - [Sulfadiazine therapy of verruca plana juvenilis].

PMID- 15439405
TI  - [Treatment of acute arachnoidal hemorrhage].

PMID- 15439406
TI  - [Milk bank of the Dutch Red Cross].

PMID- 15439408
TI  - [Size of the population in the Netherlands during the last century].

PMID- 15439407
TI  - [R. N. M. Eijkel 50 years a physician].

PMID- 15439409
TI  - [Impressions of a sojouri in Paris for purpose of attending a course of the
      UNICEF].

PMID- 15439410
TI  - [Electrical resistance of the skin during rest and emotional stress of patients
      with internal disease].

PMID- 15439411
TI  - [Case report of symptomatic psychosis].

PMID- 15439412
TI  - [Renal infantilism].

PMID- 15439413
TI  - [Rapid post-mortem diagnosis of influenza by cytologic examination of smears from
      the tracheal epithelium].

PMID- 15439414
TI  - [Results in closure of patient ductus arteriosus in 25 patients].

PMID- 15439415
TI  - [Plasma transfusion in hemophilia].

PMID- 15439416
TI  - [Plantar neuralgia].

PMID- 15439417
TI  - [Brain disease due to mercurial poisoning in an infant].

PMID- 15439418
TI  - [Significance of geriatics].

PMID- 15439419
TI  - [Endocrinology and old age].

PMID- 15439420
TI  - [Nutrition, metabolism, and old age].

PMID- 15439421
TI  - [Old age and the blood vessels].

PMID- 15439422
TI  - [Functional uterine hemorrhage during the menopause].

PMID- 15439423
TI  - [Adrenocorticotropic hormone (ACTH)].

PMID- 15439424
TI  - [Effect of a single injection of ACTH; clinical function test of the adrenal
      cortex].

PMID- 15439425
TI  - [Policlinic diagnosis of testicular tumors].

PMID- 15439426
TI  - [Subacute bacterial endocarditis, probably caused by Corynebacterium
      pseudodiphthericum (Hofmann's bacillus)].

PMID- 15439427
TI  - [Colloid degeneration of the skin, an unusual collagen disease].

PMID- 15439428
TI  - [Determination of pyroracemic acid in the blood].

PMID- 15439429
TI  - [Mineral metabolism in the animal organism; cobalt].

PMID- 15439430
TI  - [Permeable structures in the dental enamel].

PMID- 15439431
TI  - [Organ-specific antigens in the lens rudiment].

PMID- 15439432
TI  - [Development of the ductus arteriosus in man and rat].

PMID- 15439433
TI  - [Anthropogeny and sexual dimorphism].

PMID- 15439434
TI  - [An adaptation of the "chi 2 test of significance" in the investigation of
      paternity].

PMID- 15439435
TI  - [Effect of lithium upon ascidian ova; mosaic development and regulation].

PMID- 15439436
TI  - [Physiologic circulation of the cerebrospinal fluid in sauropsidian embryos].

PMID- 15439437
TI  - [Demonstration of the topography of the taenia chorioidea ventriculi IV, the
      bulla mediana laminae tectoriae, and the development of Luschka's foramina in
      human fetus from the beginning of the fifth month].

PMID- 15439438
TI  - [Acalculia].

PMID- 15439439
TI  - [Psychism and mechanism].

PMID- 15439441
TI  - [The Terman and Miles attitude-interest analysis test and experiments with a
      Dutch adaptation].

PMID- 15439440
TI  - [Psychic energy].

PMID- 15439442
TI  - [Problem of the use of narcoanalysis in forensic psychiatry].

PMID- 15439443
TI  - [Perplexity symptom in acute endogenous psychoses].

PMID- 15439444
TI  - [Genealogical examination of the nature of psychotic disorders associated with
      brain tumor].

PMID- 15439445
TI  - [Unilateral chorea].

PMID- 15439446
TI  - [Note on preceding article].

PMID- 15439447
TI  - [Clinical aspects of cerebral injury; generalized posttraumatic organic and vital
      disorders].

PMID- 15439448
TI  - [Collapse and shock following peripheral injuries and their relation to the
      concussion syndrome].

PMID- 15439449
TI  - [The cramp syndrome in local anesthesia, a manifestation of reflex epilepsy].

PMID- 15439450
TI  - [Presentation of an unusually advanced case of osteomalacia].

PMID- 15439451
TI  - [Encopresis in childhood].

PMID- 15439452
TI  - [Diagnosis and treatment of intervertebral disk hernia].

PMID- 15439453
TI  - [Indications for aeromyelography and peridurography in hernia of lumbar
      intervertebral disk].

PMID- 15439454
TI  - [Significance of aeromyelography, with special reference to the diagnosis of
      intervertebral disk hernia].

PMID- 15439455
TI  - [Roentgenography of the peridural space and its diagnostic significance].

PMID- 15439456
TI  - [Methods of measuring intracranial pressure].

PMID- 15439457
TI  - [Investigation of pressure of the cerebrospinal fluid in compression of the
      spinal cord].

PMID- 15439458
TI  - [Problem of atypical encephalitis].

PMID- 15439459
TI  - [Psychopathology of idiocy].

PMID- 15439460
TI  - Short-analytic therapy.

PMID- 15439461
TI  - Briefer psychotherapy in psychosomatic disorders of children and adolescents.

PMID- 15439462
TI  - Treatment of character-conditioned hostility in adolescents.

PMID- 15439463
TI  - Psychotherapy through child guidance.

PMID- 15439464
TI  - The short-term adjustment clinic of Beth David Hospital in New York City.

PMID- 15439465
TI  - SOME short-term considerations regarding institutional care of mentally sick
      children, by A. B. C. Anonymous.

PMID- 15439466
TI  - Brief psychological measures.

PMID- 15439467
TI  - A community agency experiment with short-term methods.

PMID- 15439468
TI  - Medical psychotherapy (psychiatry) and nonmedical psychotherapy.

PMID- 15439469
TI  - [V. M. Bekhterev as pioneer of contemporary teaching on the relation of the
      cerebral cortex and internal organs].

PMID- 15439470
TI  - [Pathogenesis of certain psychotic states in injuries of internal organs].

PMID- 15439471
TI  - [Clinical aspects of tumor of the third ventricle].

PMID- 15439472
TI  - [Endo- and exogenous correlation according to data of pediatric psychiatry].

PMID- 15439473
TI  - [Role of infection in the etiology of schizophrenia].

PMID- 15439474
TI  - [Problem of therapy at the present state of development of psychiatry in Soviet
      Union].

PMID- 15439475
TI  - [Combined therapy of psychiatric patients with electric shock and sleep].

PMID- 15439476
TI  - [Combined therapy of endogenous psychoses with alternating electroshock and
      sleep].

PMID- 15439477
TI  - [Experiments with physical exercises for inhibited and agitated catatonics].

PMID- 15439478
TI  - [Prefrontal leukotomy in certain psychiatric diseases].

PMID- 15439479
TI  - [Psycho-pathologic syndromes in chronic mercury poisoning].

PMID- 15439480
TI  - [Psychoses treated with insulin according to data of Tambov's psychiatric
      hospital].

PMID- 15439481
TI  - [Dilantin therapy of traumatic convulsive syndromes].

PMID- 15439482
TI  - [Catamnesis in schizophrenia treated by various methods].

PMID- 15439483
TI  - [Clinical aspects and pathohistology of psychotic states in intoxication with
      tetra-ethyl lead].

PMID- 15439484
TI  - [Psychosis caused by mushroom poisoning].

PMID- 15439485
TI  - [Application of a new preparation of calcium, ossocalcinol, in neurological
      practice].

PMID- 15439486
TI  - [Method of the treatment of nocturnal enuresis].

PMID- 15439487
TI  - [Pathologic and anatomic modifications in the brain in hypertension].

PMID- 15439488
TI  - [Critical review of certain scientific works of the Serbskii's Institute of
      Criminal Psychiatry].

PMID- 15439489
TI  - [VASILII Konstantinovich Khoroshko].

PMID- 15439490
TI  - [TIKHON Ivanovich Iudin].

PMID- 15439491
TI  - Necessity for exploratory thoracotomy after negative bronchoscopy.

PMID- 15439492
TI  - Today's trends in medical education.

PMID- 15439493
TI  - Treatment of congestive heart failure in ambulatory patients with salyrgan
      theophylline administered orally.

PMID- 15439494
TI  - Bile peritonitis complicating needle biopsy of liver.

PMID- 15439495
TI  - Allergy.

PMID- 15439496
TI  - WEEKLY clinicopathological exercises; recurrent hypernephroma involving wall of
      descending colon, with multiple intraperitoneal abscess from perforation of bowel
      in this region by toothpick.

PMID- 15439497
TI  - WEEKLY clinicopathological exercises; malignant lymphoma, giant-follicle type, of
      liver and spleen.

PMID- 15439498
TI  - The study of congenital anomalies by the epidemiologic method with a
      consideration of retrolental fibroplasia as an acquired anomaly of the fetus.

PMID- 15439499
TI  - The treatment of scabies in an institution: comparative study.

PMID- 15439500
TI  - Aureomycin; in vivo and in vitro observations in a clinical laboratory.

PMID- 15439501
TI  - Ectopic pregnancy in a patient with three fallopian tubes.

PMID- 15439502
TI  - Diabetes mellitus.

PMID- 15439503
TI  - WEEKLY clinicopathological exercises; papillary carcinoma of kidney, with lymph
      node metastasis; nephrolithiasis.

PMID- 15439504
TI  - WEEKLY clinicopathological exercises; squamous-cell carcinoma, grade I, of lung,
      with massive hemoptyses; bronchiectasis.

PMID- 15439505
TI  - Total uterine sampling; a proposed aid in the early cytologic detection of
      cancer.

PMID- 15439506
TI  - An evaluation of reported poisonings by acetylsalicylic acid.

PMID- 15439507
TI  - Endocarditis due to Escherichia coli.

PMID- 15439509
TI  - Diabetes mellitus.

PMID- 15439508
TI  - Sporotrichosis in New Hampshire.

PMID- 15439510
TI  - WEEKLY clinicopathological exercises; arteriosclerotic aneurysms of both iliac
      arteries and abdominal and descending thoracic aorta.

PMID- 15439511
TI  - WEEKLY clinicopathological exercises; carcinoma of head of pancreas, with
      metastases to regional lymph nodes and massive metastases to liver.

PMID- 15439512
TI  - Multiple-balloon kymographic recording of the comparative action of demerol,
      morphine and placebos on the motility of the upper small intestine in man.

PMID- 15439513
TI  - Observations on the management of hypertension by the Kempner rice diet.

PMID- 15439514
TI  - Medical aspects of civilian defense.

PMID- 15439515
TI  - Aureomycin in the treatment of amebiasis.

PMID- 15439516
TI  - Vitamin B12 and pernicious anemia.

PMID- 15439517
TI  - WEEKLY clinicopathological exercises; coronary sclerosis; myocardial infarct;
      acute fibrinous pericarditis.

PMID- 15439518
TI  - WEEKLY clinicopathological exercises; adenocarcinoma of jejunum, with metastases
      to regional lymph nodes.

PMID- 15439519
TI  - Family studies in preventive pediatrics.

PMID- 15439521
TI  - Intestinal lipodystrophy (Whipple's disease); report of a case.

PMID- 15439520
TI  - Psychiatric factors in essential hypertension; follow-up study of 74 cases.

PMID- 15439522
TI  - Liquor adulterated with lye as a cause of dysphagia and stricture of the
      esophagus.

PMID- 15439523
TI  - Vitamin B12 and pernicious anemia.

PMID- 15439524
TI  - WEEKLY clinicopathological exercises; carcinoma of remnant of gall bladder, with
      extension into hepatic ducts; choledocholithiasis.

PMID- 15439525
TI  - WEEKLY clinicopathological exercises; astrocytoma of cerebellum.

PMID- 15439526
TI  - Anomalies of the gastrointestinal tract; a review of the literature and report of
      two unusual cases.

PMID- 15439527
TI  - Therapeutic experiences with subacute bacterial endocarditis, with special
      reference to the failures.

PMID- 15439528
TI  - Febrile thrombopenic purpura with hemolytic anemia and platelet thrombosis.

PMID- 15439529
TI  - Hypertension.

PMID- 15439530
TI  - WEEKLY clinicopathological exercises; uremia due to low-salt diet; myocardial
      infarction.

PMID- 15439531
TI  - WEEKLY clinicopathological exercise; adenocarcinoma of cecum; chronic radiation
      enteritis.

PMID- 15439532
TI  - Adenoma of the islands of Langerhans; its differentiation from functional
      hypoglycemia.

PMID- 15439533
TI  - The management of simple fracture of the clavicle in adults.

PMID- 15439534
TI  - Thromboangiitis obliterans in women; possible relation to rheumatic disease.

PMID- 15439535
TI  - Hypertension.

PMID- 15439536
TI  - WEEKLY clinicopathological exercises; glomerulonephritis, acute; intracerebral
      hemorrhage, right.

PMID- 15439537
TI  - WEEKLY clinicopathological exercises; plasma-cell myeloma, diffuse;
      intercapillary glomerulosclerosis; lower-nephron nephrosis.

PMID- 15439538
TI  - Renal changes in gout.

PMID- 15439539
TI  - Pleural-fluid eosinophilia.

PMID- 15439540
TI  - Plasmacytoma of lymph node; report of a case with multiple myeloma.

PMID- 15439541
TI  - Cardiac catheterization.

PMID- 15439542
TI  - WEEKLY clinicopathological exercises: Marfan's syndrome; aneurysm of ascending
      aorta, with rupture; idiopathic medionecrosis of aorta; cardiac hypertrophy and
      dilatation; arachnodactyly.

PMID- 15439543
TI  - WEEKLY clinicopathological exercises; polyarteritis nodosa; glomerulonephritis,
      hemorrhagic, acute, diffuse; polyserositis.

PMID- 15439544
TI  - Rational therapy for secondary amenorrhea.

PMID- 15439545
TI  - Public medical care in Great Britain and the Scandinavian countries; basic
      policies.

PMID- 15439546
TI  - Massive hematemesis resulting from rupture of a gastric-artery aneurysm; report
      of 3 cases.

PMID- 15439547
TI  - The "milk factor" in carcinoma of the human breast; an analysis of 88 cases.

PMID- 15439548
TI  - The milk factor in the transmission of mammary carcinoma.

PMID- 15439549
TI  - WEEKLY clinicopathological exercises; syndrome of lower accessory pulmonary
      artery, with intralobular sequestration of lung.

PMID- 15439550
TI  - WEEKLY clinicopathological exercises; carcinoma of stomach, with retroperitoneal
      metastases and infiltration of ureters; uremia.

PMID- 15439551
TI  - Recent developments in the diagnosis of congenital heart disease.

PMID- 15439553
TI  - Congenital malformations of the heart and great vessels benefited by surgery; a
      brief review.

PMID- 15439552
TI  - Application of newer diagnostic methods in congenital heart disease.

PMID- 15439554
TI  - Complications of coronary occlusion.

PMID- 15439555
TI  - Arthrodesis of the adult knee: with special reference to Charcot's joint.

PMID- 15439556
TI  - Congenital megacolon (Hirschsprung's disease); report of 2 cases in early
      infancy.

PMID- 15439557
TI  - Dysfunction of the temporomandibular joint.

PMID- 15439558
TI  - Assurances as to the advantages and safety of radioactive iodine treatment of
      hyperthyroidism.

PMID- 15439559
TI  - Myocarditis.

PMID- 15439560
TI  - Malingering.

PMID- 15439561
TI  - The prevention of deafness.

PMID- 15439562
TI  - Streptomycin therapy for childhood tularemia.

PMID- 15439564
TI  - Notes on medical history of the Panama Canal.

PMID- 15439563
TI  - Studies of the diets of pregnant women in Mississippi: II diet patterns.

PMID- 15439566
TI  - Psychogenic factors of nonspecific chronic ulcerative colitis.

PMID- 15439565
TI  - The treatment of rheumatoid arthritis with particular reference to the use of
      cortisone and ACTH.

PMID- 15439567
TI  - Postpartal psychotic reactions.

PMID- 15439568
TI  - Treatment and prevention of cardiovascular emergencies.

PMID- 15439570
TI  - The management of infertility.

PMID- 15439571
TI  - The treatment of occiput-posterior positions.

PMID- 15439569
TI  - The prophylaxis of intravascular clotting by the use of alpha tocopherol and
      calcium.

PMID- 15439572
TI  - Considerations in the diagnosis of ectopic pregnancy.

PMID- 15439573
TI  - Carcinoma of the lung.

PMID- 15439574
TI  - A preliminary report on experimental studies of the frozen homologous aortic
      graft.

PMID- 15439575
TI  - Present progress--and the future.

PMID- 15439576
TI  - Seeking cooperation.

PMID- 15439577
TI  - Treatment of hyperthyroidism with radioiodine.

PMID- 15439578
TI  - Individual initiative.

PMID- 15439579
TI  - Medical uses of P32.

PMID- 15439581
TI  - CARE of hand injuries. VI. Open fractures.

PMID- 15439580
TI  - The concept of normality and the neurotic process.

PMID- 15439582
TI  - The use of radioactive sodium in the diagnosis of peripheral circulation in
      peripheral arteriosclerosis.

PMID- 15439583
TI  - Rehabilitation of the cardiac.

PMID- 15439584
TI  - Physiological studies of the thyroid using radioactive iodine.

PMID- 15439585
TI  - THE A.M.A. has adopted a resolution which may spell an end to the problem of
      corporate medicine vs private practice.

PMID- 15439586
TI  - Ultrasound and medicine.

PMID- 15439588
TI  - Accreditation, a plan to improve dentistry-laboratory relations.

PMID- 15439587
TI  - An histologic study of gingiva exposed to an ammoniated dentifrice.

PMID- 15439589
TI  - The technic for an improved cast crown.

PMID- 15439590
TI  - The airdent unit and the airbrasive technic.

PMID- 15439591
TI  - Mucocele of the lip.

PMID- 15439593
TI  - The development and dissemination of oral cancer.

PMID- 15439592
TI  - Maxillary cyst.

PMID- 15439594
TI  - The objectives of dental health education.

PMID- 15439595
TI  - An evaluation of the aspects of caries and its control by ammoniated dentifrices.

PMID- 15439596
TI  - Massachusetts Department of Public Health Dental Research Project.

PMID- 15439597
TI  - SYMPOSIUM: What are the duties of the dental hygienist?

PMID- 15439598
TI  - PANEL discussion: Chronic alcoholism as medical problem.

PMID- 15439599
TI  - A review of chloroform anesthesia in obstetrics.

PMID- 15439600
TI  - Respiratory complications associated with demerol.

PMID- 15439601
TI  - Hay fever, humidity, and sinusitis.

PMID- 15439602
TI  - The management of acute pancreatitis.

PMID- 15439603
TI  - Anticoagulants in treatment of coronary occlusion with myocardial infarction; a
      study of 8 cases.

PMID- 15439604
TI  - Evaluation of a potentiated antihistaminic ointment.

PMID- 15439605
TI  - Masculinizing lipid cell tumor of the ovary.

PMID- 15439606
TI  - Amenorrhea and spontaneous intraperitoneal hemorrhage in association with
      granulosa-cell carcinoma of the ovary.

PMID- 15439607
TI  - Hemiplegia associated with roseola infantum (exanthum subitum).

PMID- 15439608
TI  - Fundamental concepts of autonomic function.

PMID- 15439609
TI  - The clinical manifestations of autonomic dysfunction.

PMID- 15439610
TI  - Surgery of the autonomic nervous system: indications and results.

PMID- 15439611
TI  - Transient cardiac arrhythmia following thyroidectomy.

PMID- 15439612
TI  - Newer concepts of chronic cor pulmonale.

PMID- 15439613
TI  - The results of surgical therapy of congenital cardiovascular anomalies.

PMID- 15439614
TI  - The problem of bilateral multilobar bronchiectasis.

PMID- 15439615
TI  - The quantitative replacement of blood volume deficits in the surgical patient.

PMID- 15439616
TI  - Fetal and neonatal mortality.

PMID- 15439617
TI  - The association of Meigs's syndrome with Krukenberg tumors.

PMID- 15439618
TI  - Mediastinal ganglioneuroma in children.

PMID- 15439619
TI  - Suffocative goiter in newborn infant.

PMID- 15439620
TI  - Solitary pulmonary metastasis with detectable bronchial involvement appearing
      nine and a half years after resection of colon carcinoma.

PMID- 15439621
TI  - Complete recovery of a case of spindle cell and oval cell sarcoma with a five
      year follow-up.

PMID- 15439622
TI  - The treatment of acne vulgaris.

PMID- 15439624
TI  - The impact of psychiatry on therapy in dermatology.

PMID- 15439623
TI  - Seborrheic dermatitis; supplemental treatment with vitamin B12.

PMID- 15439625
TI  - Further experiments on prolonging local anesthesia with insoluble anesthetic
      bases.

PMID- 15439626
TI  - Control of tinea capitis.

PMID- 15439627
TI  - N-Ethylo-o-crotono-toluide (eurax) as an antipruritic.

PMID- 15439628
TI  - The treatment of localized (pretibial) myxedema with hyaluronidase.

PMID- 15439629
TI  - Failure of undecylenic acid to cure psoriasis.

PMID- 15439630
TI  - Pneumoperitoneum versus pneumothorax.

PMID- 15439631
TI  - Chronic biliary disease in general practice.

PMID- 15439632
TI  - Treatment of backaches by infiltration of anesthetic oils.

PMID- 15439633
TI  - Application of epithelial grafts to oral and other facial cavities.

PMID- 15439634
TI  - Acute porphyria in a Negro.

PMID- 15439635
TI  - Cervical lung hernia associated with a substernal thyroid.

PMID- 15439636
TI  - Retention of pregnancy for eighty-seven days after premature rupture of
      membranes.

PMID- 15439637
TI  - Treatment of tularemia with aureomycin.

PMID- 15439638
TI  - The value of proctoscopy as a routine examination in preventing deaths from
      cancer of the large bowel.

PMID- 15439639
TI  - Cholinergic and anticholinergic drugs and their trial in treatment of
      gastrointestinal disorders; trial of urecholine and banthine.

PMID- 15439641
TI  - Diarrheal diseases--a new specialty.

PMID- 15439640
TI  - The incidence of amebiasis in the Albany (New York) area.

PMID- 15439642
TI  - Acute pancreatitis: further observations of value in its recognition.

PMID- 15439643
TI  - Therapeutic trends and management in advanced carcinoma of the colon and rectum.

PMID- 15439644
TI  - A newer concept in the management of chronic ulcerative colitis.

PMID- 15439645
TI  - Chloromycetin therapy in chronic ulcerative colitis.

PMID- 15439646
TI  - Rehabilitation of the lower extremity amputee in a large general hospital.

PMID- 15439647
TI  - Experimental study of a synthetic breast milk for infant feeding formula.

PMID- 15439648
TI  - Immediate tendon repair with fascia lata transference in a compound fracture
      treated with aureomycin.

PMID- 15439649
TI  - WHAT about blindness in our state?

PMID- 15439650
TI  - MEDICAL Society of the State of New York, House of Delegates; minutes of the
      annual meeting, May 8-10, 1950.

PMID- 15439651
TI  - Health and medical services for agricultural workers in the tropics.

PMID- 15439652
TI  - Appraisal of industrial health examinations.

PMID- 15439653
TI  - Serologic tests for cancer.

PMID- 15439654
TI  - Clinical evaluation of aureomycin, chloramphenicol, and terramycin.

PMID- 15439656
TI  - Working minimum of hepatic function tests for rationalizing the treatment of
      jaundice.

PMID- 15439655
TI  - Newer insulins with special reference to NPH insulin.

PMID- 15439657
TI  - Periodic disease.

PMID- 15439658
TI  - The reduction of mortality from abortion.

PMID- 15439659
TI  - Intestinal obstruction due to gallstones diagnosed preoperatively.

PMID- 15439660
TI  - Adenoacanthoma of the uterus.

PMID- 15439661
TI  - Cardiopericardiopexy for the treatment of coronary arterial disease.

PMID- 15439662
TI  - Typhoid fever successfully treated with chloramphenicol in a two-year-old child.

PMID- 15439663
TI  - Postpartum pelvic hematoma.

PMID- 15439664
TI  - Mixed tumor of salivary gland type in the nose.

PMID- 15439665
TI  - Rocky Mountain spotted fever.

PMID- 15439666
TI  - The doctor's responsibility in child adoption.

PMID- 15439667
TI  - Immediate orthodontics.

PMID- 15439668
TI  - Medical aspects of oral diagnosis.

PMID- 15439669
TI  - Hemi-resection of the mandible and neuro-muscular adaptation.

PMID- 15439670
TI  - Development of the dentition.

PMID- 15439671
TI  - Removal of broken hypodermic needle.

PMID- 15439672
TI  - The president's address.

PMID- 15439673
TI  - Mars and Aesculapius.

PMID- 15439674
TI  - Standards in medicine.

PMID- 15439675
TI  - Chloroform in obstetrics.

PMID- 15439676
TI  - A study of early ambulation.

PMID- 15439677
TI  - Studies on the pathogenesis of rheumatic fever; the antistreptolysin titre in
      acute tonsillitis, in patients admitted for tonsillectomy, in rheumatic fever and
      in control groups.

PMID- 15439678
TI  - Some advances in the treatment of skin diseases.

PMID- 15439679
TI  - The practical aspects of some current aero-medical problems.

PMID- 15439680
TI  - The position of research and diagnosis of viral disease in the United States of
      America.

PMID- 15439681
TI  - Spontaneous compression of the median nerves in the carpal tunnel.

PMID- 15439682
TI  - Healing of a pathological fracture by hormone therapy.

PMID- 15439683
TI  - Karitane hospitals; admissible and non-admissible cases and the procedure
      governing admission.

PMID- 15439684
TI  - The endocrine approach to arthritis.

PMID- 15439685
TI  - The treatment of high blood pressure with hexamethonium iodide.

PMID- 15439686
TI  - Reflections on the postpartum period.

PMID- 15439687
TI  - Antepartum hemorrhages.

PMID- 15439688
TI  - Accidents in the home; a study of patients admitted to Auckland Hospital, April,
      1948-March, 1949.

PMID- 15439689
TI  - Tuberculous meningitis treated with streptomycin: a preliminary report.

PMID- 15439690
TI  - Primary union in the operation for fistula-in-ano.

PMID- 15439691
TI  - The present position of treatment of carcinoma of the breast.

PMID- 15439692
TI  - Virus infections of the nervous system.

PMID- 15439693
TI  - The comparative value of curarizing agents with special reference to convulsion
      therapy.

PMID- 15439694
TI  - Chronic beri-beri heart disease; report of a case.

PMID- 15439695
TI  - Unusual tumours of the superior mediastinum; a report of two cases.

PMID- 15439696
TI  - Spontaneous rupture of the esophagus; report of a case.

PMID- 15439697
TI  - The after-treatment of amputation stumps.

PMID- 15439698
TI  - Emotional aspects of essential hypertension.

PMID- 15439699
TI  - Evaluation of x-ray examination in sinusitis.

PMID- 15439700
TI  - [Diseases of the circulatory system as a public health problem].

PMID- 15439701
TI  - [A case of rhabdomyosarcoma].

PMID- 15439702
TI  - [Permeability and diffusibility of the enamel as a factor in dental caries].

PMID- 15439703
TI  - [Journal articles, a link in dental information].

PMID- 15439704
TI  - [Gathering mercury and amalgam scrapings].

PMID- 15439705
TI  - Spaying on the King Ranch.

PMID- 15439706
TI  - The physiology of disease; the anemias.

PMID- 15439707
TI  - Address of the president.

PMID- 15439708
TI  - Canine obstetrics.

PMID- 15439709
TI  - Receiving and dismissing patients in a small-animal hospital.

PMID- 15439710
TI  - Oxygen and oxygen equipment.

PMID- 15439711
TI  - Clinical interpretation of laboratory reports.

PMID- 15439712
TI  - Practical considerations in the diagnosis of the jaundiced patient.

PMID- 15439713
TI  - The changing emphasis in communicable disease control.

PMID- 15439714
TI  - "Antabuse" in the treatment of chronic alcoholism.

PMID- 15439715
TI  - Obesity and hypertension: the importance of a safe compound to control appetite;
      report of a series of 100 cases.

PMID- 15439717
TI  - Operative results in prostatic surgery.

PMID- 15439716
TI  - Phonocardiograms in patent ductus arteriosus.

PMID- 15439718
TI  - The modern treatment of typhoid fever; with report of a case.

PMID- 15439719
TI  - Esophageal resection, upper third, with end-to-end anastomosis; a case report.

PMID- 15439720
TI  - Exfoliative dermatitis due to phenobarbital ending fatally.

PMID- 15439721
TI  - PHYSICIANS of North Carolina: Thomas Fanning Wood.

PMID- 15439722
TI  - CLINICOPATHOLOGIC conference; postnecrotic cirrhosis of the liver with portal
      obstruction.

PMID- 15439723
TI  - Streptomycin in tuberculous meningitis; report of case with recovery, observed
      over three years, with unusual bacteriologic findings.

PMID- 15439724
TI  - Let us do something.

PMID- 15439725
TI  - Clinical potassium deficiencies; mechanism of potassium deficiency.

PMID- 15439726
TI  - Endocrine factors in psychic disturbances.

PMID- 15439727
TI  - Value of para-aminobenzoic acid and aureomycin in treatment of Rocky Mountain
      spotted fever.

PMID- 15439728
TI  - What can happen when diabetics marry.

PMID- 15439729
TI  - The problem of varicose veins.

PMID- 15439731
TI  - Sterility.

PMID- 15439730
TI  - Diverticulum of female urethra.

PMID- 15439732
TI  - Lower nephron nephrosis.

PMID- 15439733
TI  - The esophageal electrocardiogram.

PMID- 15439734
TI  - Nerve blocks as an aid in the diagnosis and therapy of disease.

PMID- 15439735
TI  - Neurologic syndromes about the face and head.

PMID- 15439736
TI  - Dr. D. S. Maynard, pioneer physician of Seattle.

PMID- 15439737
TI  - Some current medical aspects of thyroid disease.

PMID- 15439738
TI  - Some surgical aspects of thyroid disease.

PMID- 15439739
TI  - Tumors of the thyroid gland.

PMID- 15439740
TI  - [The role of interattico-tympanic diaphragm in the pathogenesis of otitis in
      infants].

PMID- 15439741
TI  - [Surgical therapy of tumors of the mediastinum in infants; exeresis of a
      mediastinal dysembryoma of thymic origin in a 15-month child].

PMID- 15439742
TI  - [Disastrous consequences of an anti-Rh isoimmunization caused by several
      intramuscular injections of maternal blood].

PMID- 15439743
TI  - [Three cases of transplacental tuberculosis of infants].

PMID- 15439744
TI  - [Investigation of rural rickets in Correze].

PMID- 15439745
TI  - [Lactarium and breast pump].

PMID- 15439746
TI  - [The third fontanelle].

PMID- 15439747
TI  - [Human infection due to Vibrio foetus].

PMID- 15439748
TI  - [The psychomotor state of hypotrophic infants; the need for preventive psychiatry
      in infants' homes].

PMID- 15439749
TI  - [The crowding of hospital nurseries; Hopital Trousseau, 1949].

PMID- 15439750
TI  - [Clinical and radiological considerations on adamantinomas].

PMID- 15439751
TI  - [Orthodontics].

PMID- 15439752
TI  - Engineering in the atomic age.

PMID- 15439753
TI  - Use of the pile for chemical analysis.

PMID- 15439754
TI  - Distributed beta sources in uniformly absorbing media-1.

PMID- 15439755
TI  - Improved film badge for personnel monitoring.

PMID- 15439756
TI  - Experiments with a 6-mev betatron.

PMID- 15439757
TI  - Body radium content of individuals with no known occupational exposure.

PMID- 15439758
TI  - A direct method for determining radium in exposed humans.

PMID- 15439759
TI  - Argonne National Laboratory; relationships with industry.

PMID- 15439760
TI  - Fluorescence of liquids under gamma bombardment.

PMID- 15439761
TI  - Alpha radioactivity and the stability of heavy nuclei.

PMID- 15439762
TI  - Distributed beta sources in uniformly absorbing media.

PMID- 15439763
TI  - Biological syntheses of radioisotope-labeled compounds.

PMID- 15439764
TI  - Practical aspects of surface decontamination.

PMID- 15439765
TI  - Cavity ionization chamber for measurement of absorbed x-radiation energy.

PMID- 15439766
TI  - What are the prospects for industrial nuclear power?

PMID- 15439767
TI  - Insect bites: prevention and treatment.

PMID- 15439769
TI  - Influenzal meningitis.

PMID- 15439768
TI  - MENTAL care through six centuries.

PMID- 15439770
TI  - Training within industry on the district; prevention of drop feet.

PMID- 15439771
TI  - AFRICAN midwife.

PMID- 15439772
TI  - HOSPITAL right motor service.

PMID- 15439773
TI  - Aftercare of the hospital patient.

PMID- 15439774
TI  - Extra membranous pregnancy.

PMID- 15439775
TI  - Abdominal pregnancy.

PMID- 15439776
TI  - THE HEALTH visitor as family educator; W.P.H.O.A. Summer School at Oxford.

PMID- 15439777
TI  - Surgical treatment of peptic ulcers.

PMID- 15439778
TI  - Training within industry on the district; rotunda douche technique.

PMID- 15439779
TI  - AFRICAN midwife.

PMID- 15439780
TI  - Emergency nephrectomy for violent haematuria.

PMID- 15439781
TI  - Haemolytic disease of the newborn.

PMID- 15439782
TI  - Blue baby operation for congenital heart disease.

PMID- 15439783
TI  - BLUE baby operation for congenital heart disease.

PMID- 15439784
TI  - Skin manifestations of diseases.

PMID- 15439785
TI  - I. Prevention of sterility; 2. post-natal care.

PMID- 15439786
TI  - Diaphragmatic hernia of stomach with ulceration.

PMID- 15439787
TI  - Melancholia.

PMID- 15439788
TI  - THE SITING and planning of hospitals.

PMID- 15439789
TI  - Nursing in Pakistan.

PMID- 15439790
TI  - Training within industry on the district; non-touch surgical dressing technique.

PMID- 15439791
TI  - Obstetrical and gynaecological operations; operation for complete tear of
      perineum.

PMID- 15439792
TI  - Cellulitis, due to infection by Erysipelothrix rhusiopathiae.

PMID- 15439793
TI  - THE CHILD and his environment.

PMID- 15439794
TI  - PREPARATION of the private nurse for her task.

PMID- 15439795
TI  - BIRTHPLACE of Sir Alexander Fleming-Darvel, Ayrshire, August 6, 1881.

PMID- 15439796
TI  - JERSEY revisited; hospital extensions and progress.

PMID- 15439797
TI  - HOSPITAL aboard.

PMID- 15439798
TI  - PSYCHIATRIC unit in Denmark; modern block at Bispebjerg Hospital, Copenhagen.

PMID- 15439799
TI  - Satisfactions of psychiatric nursing.

PMID- 15439800
TI  - Blistered feet and blister beetles, with a postscript on snake bites.

PMID- 15439801
TI  - Introduction of labour.

PMID- 15439802
TI  - The unconscious state in head injuries.

PMID- 15439804
TI  - OLD people: well or sick.

PMID- 15439803
TI  - The care of the aged.

PMID- 15439805
TI  - Hospital nursing in Kalimpong.

PMID- 15439806
TI  - Cardiac massage for heart failure during operation for ligature of varicose
      veins.

PMID- 15439807
TI  - Obstetrical and gynaecological operations; repair operation for uterovaginal
      prolapse.

PMID- 15439808
TI  - Letters from bed, I.

PMID- 15439809
TI  - Q.A.R.A.N.C. "other ranks" in training; new development in army nursing service.

PMID- 15439811
TI  - A decade of immunisation.

PMID- 15439810
TI  - CORPORATE seals; some new designs for the National Health Service.

PMID- 15439812
TI  - Male nurse's hobby: collecting butterflies and moths.

PMID- 15439813
TI  - NURSING officers and other ranks; Q.A.R.A.N.C. depot in its new home at Ontario
      Camp, Hindhead.

PMID- 15439814
TI  - FOREIGN draft.

PMID- 15439815
TI  - Application of psychiatry to home nursing.

PMID- 15439816
TI  - Letters from bed-II.

PMID- 15439817
TI  - Eugenics and the influence of heredity.

PMID- 15439818
TI  - The bone bank.

PMID- 15439819
TI  - Obstetrical and gynaecological operations; fascial sling operation for stress
      incontinence.

PMID- 15439820
TI  - NURSING superintendent with the British Red Cross.

PMID- 15439821
TI  - POST-GRADUATE course in cancer nursing at the Christie Hospital and Holt Radium
      Institute, Manchester.

PMID- 15439822
TI  - Anterior poliomyelitis.

PMID- 15439823
TI  - STUDENT nurse training in Geneva, at the Bon Secours School of Nursing.

PMID- 15439824
TI  - The future of the midwife in Scotland.

PMID- 15439826
TI  - Women in public health.

PMID- 15439825
TI  - A unit for premature babies.

PMID- 15439827
TI  - Visiting the child patient.

PMID- 15439828
TI  - POISE House, Stockport, serving the Stockport and Boxton area.

PMID- 15439829
TI  - NURSES Act, 1949: its educational scope and potentialities.

PMID- 15439830
TI  - The prevention of tuberculosis; introductory lecture of a study day on
      tuberculosis.

PMID- 15439831
TI  - INTERNATIONAL campaign against tuberculosis with BCG vaccination.

PMID- 15439832
TI  - The assistant nurse; are training standards falling?

PMID- 15439833
TI  - VISITING eleven countries; a report of the recent tour of Dame Katherine Watt.

PMID- 15439834
TI  - St. Andrew's Mission Hospital, Singapore.

PMID- 15439836
TI  - WARD Sister's conference.

PMID- 15439835
TI  - Clinical instruction.

PMID- 15439837
TI  - Scandinavian Congress for Northern Nurses.

PMID- 15439838
TI  - Visiting eleven countries.

PMID- 15439839
TI  - CLINICAL teaching in a Norwegian hospital.

PMID- 15439840
TI  - The allergic child.

PMID- 15439842
TI  - Revisiting America and Canada.

PMID- 15439841
TI  - TRAINING and education of the specialist nurse; a report of the Conference of the
      Public Health Section of the Royal College of Nursing.

PMID- 15439843
TI  - A professional library for public health nurses.

PMID- 15439844
TI  - Carbon tetrachloride poisoning.

PMID- 15439845
TI  - TEACHING psychology to junior student nurses.

PMID- 15439846
TI  - ROYAL Masonic Hospital Nursing School.

PMID- 15439848
TI  - BELFAST Royal Maternity Hospital.

PMID- 15439847
TI  - A suggested two year training for the general register.

PMID- 15439849
TI  - Aspects of modern treatment of tuberculosis, with special reference of
      streptomycin, illustrated by a series of x-rays.

PMID- 15439850
TI  - Revisiting North America; industrial problems.

PMID- 15439851
TI  - PREPARATION of the private nurse for her task.

PMID- 15439852
TI  - Problems of the school child.

PMID- 15439853
TI  - Acute otitis media with discharge.

PMID- 15439854
TI  - ST. RICHARD'S Hospital, a modern hospital and training school in historic
      Chichester.

PMID- 15439855
TI  - BRITISH Rheumatic Association.

PMID- 15439856
TI  - GLOUCESTERSHIRE refresher course for health visitors.

PMID- 15439857
TI  - Revisiting North America.

PMID- 15439858
TI  - How to avoid the early waking of patients.

PMID- 15439859
TI  - Acute rheumatism complicated by pericarditis, peritonitis and pneumonia: a case
      history.

PMID- 15439860
TI  - MEDICINE in 1850.

PMID- 15439861
TI  - CONFERENCE at Harrogate on social work.

PMID- 15439862
TI  - HOSTEL for employed paraplegics; the Ministry of Pensions scheme.

PMID- 15439863
TI  - FOR student nurses: preliminary examinations: elementary anatomy, physiology and
      hygiene.

PMID- 15439864
TI  - Some aspects of health and welfare supervision.

PMID- 15439865
TI  - Treating infantile diarrhoea in former times.

PMID- 15439867
TI  - Children without homes.

PMID- 15439866
TI  - Sterility and allied conditions.

PMID- 15439868
TI  - The Royal Infirmary, Edinburgh.

PMID- 15439869
TI  - How to avoid the early waking of patients.

PMID- 15439870
TI  - Some aspects of health and welfare supervision.

PMID- 15439871
TI  - Holiday in Italy.

PMID- 15439872
TI  - Present status of heat-processing damage to protein foods.

PMID- 15439873
TI  - A GOITROGENIC agent in food.

PMID- 15439874
TI  - SYNTHESIS of rhodopsin.

PMID- 15439876
TI  - ALBUMIN administration to premature infants.

PMID- 15439875
TI  - THIAMINE deficiency, pyruvate metabolism, and acid secretion in stomachs of mice
      in vitro.

PMID- 15439877
TI  - VITAMIN B6 and metabolism of d-amino acids.

PMID- 15439878
TI  - CHOLINE and atherosclerosis.

PMID- 15439879
TI  - PRODUCTION of acute massive hepatic necrosis in rats by dietary means.

PMID- 15439880
TI  - BIOLOGIC estimation of vitamin A.

PMID- 15439881
TI  - MINERAL-enriched meat as a milk substitutes.

PMID- 15439882
TI  - TREATMENT of weight loss in infants.

PMID- 15439883
TI  - MECHANISM of niacin formation.

PMID- 15439884
TI  - NUTRITIONAL studies with germ-free chickens.

PMID- 15439885
TI  - PLASMA level and urinary excretion of amino acids.

PMID- 15439886
TI  - RELATION of diet to tumor incidence and growth.

PMID- 15439887
TI  - NUTRITIONAL implications of the Maillard browning reaction in foods.

PMID- 15439888
TI  - METHODS for determination of tryptophan.

PMID- 15439889
TI  - RESISTANT rickets.

PMID- 15439890
TI  - Epidemiology and nutrition surveys.

PMID- 15439891
TI  - LIPOTROPIC action of choline, betaine, and methionine in birds.

PMID- 15439892
TI  - ENRICHMENT of diet with protein.

PMID- 15439893
TI  - TOXICITY of D-amino acids.

PMID- 15439894
TI  - NITRATE in vegetables.

PMID- 15439895
TI  - DESIRABLE fat levels in the diet.

PMID- 15439896
TI  - TREATMENT of mental defectives with thiamine.

PMID- 15439898
TI  - DIETARY treatment of liver disease.

PMID- 15439897
TI  - NUTRITION and public health.

PMID- 15439899
TI  - MINERAL nutrition in rats.

PMID- 15439900
TI  - IMPROVEMENT of nutritive value of corn by plant breeding and selection.

PMID- 15439901
TI  - FORMATION and circulation of ascitic fluid.

PMID- 15439902
TI  - HEPATIC changes in pigs resulting from a cold environment.

PMID- 15439903
TI  - ESSENTIAL amino acid requirements for maintenance and for rehabilitation in rats.

PMID- 15439904
TI  - VITAMIN B12 and the baby pig.

PMID- 15439905
TI  - AMINO acid excretion in liver disease and Wilson's disease.

PMID- 15439906
TI  - [Psychic disorders in relation to gynecology].

PMID- 15439907
TI  - [Interstitial tubal pregnancy].

PMID- 15439908
TI  - [Can "mulleroma" be considered in the genesis of some forms of dysmenorrhea?].

PMID- 15439909
TI  - [Ergonovin in the third stage of labor].

PMID- 15439910
TI  - [Spermatic fluid].

PMID- 15439911
TI  - [Some medicosocial problems with respect to the law of adoption].

PMID- 15439912
TI  - [Uterine myoma and sterility].

PMID- 15439913
TI  - [Sterility and myoma].

PMID- 15439914
TI  - [Myoma and sterility].

PMID- 15439915
TI  - [A case of an Rho negative child in a marriage with maternofetal
      isoimmunization].

PMID- 15439916
TI  - [Low insertion of the placenta; influence of antibiotics in the choice of
      treatment].

PMID- 15439917
TI  - [Amniotic fluid; contribution to the study of its biological significance in
      pregnancy. I. Physicochemical aspect].

PMID- 15439918
TI  - [Prophylaxis of puerperal eclampsia].

PMID- 15439919
TI  - [Study of precocious primiparity].

PMID- 15439920
TI  - [Respiration of the fetus; thoracic movements during intrauterine life; beginning
      of extrauterine life].

PMID- 15439921
TI  - [Wertheim operation or curietherapy in cervical cancer?].

PMID- 15439922
TI  - [Streptomycin therapy in tuberculosis of female genitals].

PMID- 15439923
TI  - [Diagnostic and therapeutic problems in the study of frigidity].

PMID- 15439924
TI  - [Sterility due to tuberculosis of the female genitals].

PMID- 15439925
TI  - [Amniotic fluid. II. Contribution to its biochemical study].

PMID- 15439926
TI  - [Schwannoma of the sigmoid loop].

PMID- 15439927
TI  - [Not Available].

PMID- 15439928
TI  - [The tooth and its amino acids].

PMID- 15439930
TI  - [Composition of types of precious metal alloys in dentistry].

PMID- 15439929
TI  - [Odontalgia as a reflex in visceropathies].

PMID- 15439931
TI  - [Why, when and how to extract included canines].

PMID- 15439932
TI  - [Maxillary cysts and the technic of their removal].

PMID- 15439933
TI  - [A case of dental anomaly].

PMID- 15439934
TI  - [Experimental research in nitrous oxide anesthesia].

PMID- 15439935
TI  - [Diameter measurement of nerve fibers in human dental pulp].

PMID- 15439936
TI  - [Eruption of permanent teeth, caries frequency, variations in size of dental arch
      and intermaxillary relations in Finnish twins and triplets].

PMID- 15439937
TI  - [Effect of asymptomatic gangrene upon sedimentation rate and the blood picture as
      a whole].

PMID- 15439938
TI  - [Report on experiments with fluorine application in Goteborg school children].

PMID- 15439939
TI  - [Observations on rickets and the results of massive dose vigantol prophylaxis in
      children].

PMID- 15439940
TI  - [Epidemiologic and sociohygenic observations on two epidemics of microsporia in
      Cologne].

PMID- 15439941
TI  - [Organisation of family care].

PMID- 15439942
TI  - [Problems affecting social service].

PMID- 15439943
TI  - [Sterilization of syringes and other instruments].

PMID- 15439944
TI  - [Reticulosarcomatosis in a 7 year old child].

PMID- 15439945
TI  - [Problem of so-called idiopathic dilatation and hypertrophy of the heart].

PMID- 15439946
TI  - [Tuberculous pericarditis, with special reference to the development of Pick
      Hutinel pseudocirrhosis of the liver].

PMID- 15439947
TI  - [Hypernephroma of the liver].

PMID- 15439948
TI  - [Experience with streptomycin in tuberculous meningitis].

PMID- 15439950
TI  - [Cross infection in Heine-Medin disease; epidemiology of the disease].

PMID- 15439949
TI  - [Clinical aspect of vertebra plana].

PMID- 15439951
TI  - [Antihistamine therapy in acute nephritis].

PMID- 15439952
TI  - [Relation between panhemocytophthisis and acute myeloid leukemia].

PMID- 15439953
TI  - [Prognosis of periglandular edema in toxic diphtheria].

PMID- 15439955
TI  - [Bacteriology of human milk].

PMID- 15439954
TI  - [Prognosis of periglandular edema in toxic diphtheria].

PMID- 15439956
TI  - [Use of sheep's milk in infant feeding].

PMID- 15439957
TI  - [Panarteritis nodosa in an eight and a half year old girl].

PMID- 15439958
TI  - [Birth--traumatic avulsion of the scalp in a newborn infant].

PMID- 15439959
TI  - [Etiology of bowing tic].

PMID- 15439960
TI  - [Mass prophylaxis of tuberculosis in childhood].

PMID- 15439961
TI  - [Report on an anti-tuberculosis vaccination campaign in Vienna during 1949].

PMID- 15439962
TI  - [Ascariasis and trichuriasis in Styrian (Austrian) children].

PMID- 15439963
TI  - [Pre- and post-natal infant mortality].

PMID- 15439965
TI  - [Effect of stimulation therapy on diseases of the brain in childhood].

PMID- 15439964
TI  - [Synergy of a specific infection (streptotrichosis) in alimentary toxemia of
      infants and the newborn].

PMID- 15439966
TI  - [Possibility of clinical diagnosis of threatened nutritional disorders in
      infancy, and its significance in determination of tolerance].

PMID- 15439967
TI  - [Value of determining the pH in the stool of infants].

PMID- 15439968
TI  - [The capillaries in nutritional disorders of infancy].

PMID- 15439969
TI  - [Treatment of laryngeal diphtheria in infancy and early childhood].

PMID- 15439970
TI  - [Paradoxical leukocyte reaction].

PMID- 15439971
TI  - [Leptomeningosis haemorrhagica interna; a case of spinal leptomeningeal
      hemorrhage].

PMID- 15439972
TI  - [A primary tumor of the pericardium].

PMID- 15439973
TI  - [Reticulosarcomatosis in a three months old infant].

PMID- 15439974
TI  - [Etiology and clinical aspects of Sturge-Weber disease].

PMID- 15439975
TI  - [Treatment of subacute and chronic osteomyelitis].

PMID- 15439976
TI  - [Treatment of congenital atresia of the lacrimal ducts].

PMID- 15439977
TI  - [A case of angina vaccinalis].

PMID- 15439978
TI  - [Richard Priesel on his 60th birthday].

PMID- 15439979
TI  - [Actinomycosis of the tongue].

PMID- 15439980
TI  - [Fluorine prophylaxis of dental caries, a public problem].

PMID- 15439981
TI  - [Tonsillogenous and dentogenous recurring rheumatic endarteritis].

PMID- 15439982
TI  - [Hammered gold fillings].

PMID- 15439983
TI  - [Bernhard Gottlieb].

PMID- 15439984
TI  - [Victor Veau].

PMID- 15439985
TI  - Chloromycetin treatment of typhoid fever.

PMID- 15439986
TI  - The management of acute cholecystitis.

PMID- 15439987
TI  - Innocuity of protracted oral administration of special fermentation concentrates
      of B12 as demonstrated in a patient with acute leukemia.

PMID- 15439988
TI  - Chorionepithelioma of the fallopian tube: report of a case with autopsy.

PMID- 15439989
TI  - Intra-abdominal hemorrhage during pregnancy from the spontaneous rupture of a
      uterine vein.

PMID- 15439990
TI  - Ohio physicians in the nineteenth century, a statistical study.

PMID- 15439991
TI  - The epileptic child in school.

PMID- 15439992
TI  - Bronchoscopy in the newborn.

PMID- 15439993
TI  - Preliminary report on "at birth" diphtheria, pertussis and tetanus immunization.

PMID- 15439994
TI  - Recent concepts in the study of infertility.

PMID- 15439995
TI  - Case report: eclampsia in a fourteen-year old negress with 252 recorded
      convulsions.

PMID- 15439996
TI  - Unusual ovarian cyst developing post partum: case report.

PMID- 15439997
TI  - The advantages of ocular implants in enucleation surgery.

PMID- 15439998
TI  - A case of splenic neutropenia complicated by infectious mononucleosis after
      splenectomy.

PMID- 15439999
TI  - Ohio physicians in the nineteenth century, a statistical study.

PMID- 15440000
TI  - [Hydradenoma (syringoma) of the eyelids; report of two cases, one with corneal
      degeneration].

PMID- 15440001
TI  - [Congenital keratitis].

PMID- 15440002
TI  - [Multiform familial degeneration of the posterior membrane of the cornea].

PMID- 15440003
TI  - [Perforation of the cornea of both eyes by voluntary insertion of foreign
      bodies].

PMID- 15440004
TI  - [Keratoplasty performed during the morbid process].

PMID- 15440005
TI  - [Aculeate injuries of the eye; tolerance for more than 20 years of a bee stinger
      lodged in the cornea and anterior chamber of the eye].

PMID- 15440006
TI  - [Minute volume of the aqueous in the anterior chamber of the human eye in normal
      state and in primary glaucoma].

PMID- 15440008
TI  - [Penicillin concentration in the anterior chamber and vitreous].

PMID- 15440007
TI  - [Apparent drainage pressure, tension and pressure in the aqueous veins].

PMID- 15440009
TI  - [Nodular necrotic scleritis and its relation to scleromalacia].

PMID- 15440010
TI  - [Entoptic age phenomena].

PMID- 15440011
TI  - [Recurrent erosion].

PMID- 15440012
TI  - [Small lens loop].

PMID- 15440013
TI  - [Result of surgery in complicated cataract following uveitis; prognostic
      significance of diagnostic puncture of the anterior chamber].

PMID- 15440014
TI  - [Biomicroscopic examination of the insertion of the posterior zonular fibers to
      the lens].

PMID- 15440015
TI  - [Two cases of histologically proven tuberculous uveoparotitis].

PMID- 15440017
TI  - [Bilateral choroidal metastasis of a reticulosarcoma].

PMID- 15440016
TI  - [Prognosis in malignant melanoma of the uvea].

PMID- 15440018
TI  - [Unilateral pigmentary retinitis].

PMID- 15440019
TI  - [Rare form of orbital tumor; eosinophilic granuloma].

PMID- 15440020
TI  - [Significance of histologic findings for the classification of perforating wounds
      of the eye].

PMID- 15440021
TI  - [Preventing calcium hydroxide burns of the eye incurred by using tree sprayers to
      whitewash stalls].

PMID- 15440022
TI  - [Homonymous hemianopsia following occipital lobectomy].

PMID- 15440023
TI  - [A case of acrocephalosyndactylia].

PMID- 15440024
TI  - [Mandibulofacial dysmorphia with ocular abnormalities].

PMID- 15440025
TI  - [Plastic operations].

PMID- 15440026
TI  - [Indications and results in myectomy of the inferior obliquus oculi].

PMID- 15440027
TI  - [Further experience with prolonged iontophoresis].

PMID- 15440028
TI  - [Effect of hydergin upon intraocular and diastolic pressure of the central
      artery].

PMID- 15440029
TI  - [Mintacol Bayer, a new remedy in glaucoma].

PMID- 15440030
TI  - [Experience with p-aminosalicylic acid in treatment of tuberculous infections of
      the eye].

PMID- 15440031
TI  - [A simple turbidimeter for general practice].

PMID- 15440032
TI  - [Apparatus for testing plexiglas contact lenses].

PMID- 15440033
TI  - Experimental hypertensive uveitis in the rabbit.

PMID- 15440034
TI  - The A. O. A. Congress at Minneapolis.

PMID- 15440035
TI  - RESEARCH, orthoptics, television.

PMID- 15440036
TI  - Photography of eye-movements.

PMID- 15440037
TI  - Procedure in visual training--V.

PMID- 15440038
TI  - Deviations of the ocular muscles.

PMID- 15440039
TI  - Nature's laws and visual efficiency.

PMID- 15440040
TI  - The child's vision from the clinical approach.

PMID- 15440042
TI  - Building acuity with Plateau's spiral.

PMID- 15440041
TI  - Visual standards for safe driving.

PMID- 15440043
TI  - Procedure in visual training--VI.

PMID- 15440044
TI  - Identifying deviations by the cover test.

PMID- 15440045
TI  - Nature's laws and visual efficiency.

PMID- 15440046
TI  - Myopia from an operational viewpoint.

PMID- 15440047
TI  - AMERICAN Optometric Association educational program highlights.

PMID- 15440048
TI  - Visual development.

PMID- 15440049
TI  - Myopia from an operational viewpoint.

PMID- 15440050
TI  - A case for orthoptics.

PMID- 15440051
TI  - PRESIDENT O'Shea's report.

PMID- 15440052
TI  - Visual development.

PMID- 15440053
TI  - Report of the secretary.

PMID- 15440054
TI  - Ocular neuroses and opsiopsychopathies.

PMID- 15440056
TI  - Prescribing for the amblyope.

PMID- 15440055
TI  - Illumination and seeing.

PMID- 15440057
TI  - How to build a practice.

PMID- 15440058
TI  - Visual development.

PMID- 15440059
TI  - A case of prismatic effect.

PMID- 15440061
TI  - Visual development.

PMID- 15440060
TI  - Increasing the wearing time of contact lenses.

PMID- 15440062
TI  - Relation of refractive error to optometric tests.

PMID- 15440063
TI  - Case history; anemia as revealed in the field charts.

PMID- 15440064
TI  - Simple equipment for testing strabismic patients.

PMID- 15440065
TI  - Drivers' vision tests.

PMID- 15440066
TI  - Diagnosis and treatment of odontogenic and fissural cysts.

PMID- 15440067
TI  - The surgical treatment of cancer of the gingiva.

PMID- 15440068
TI  - Principles and technique of exodontia.

PMID- 15440069
TI  - Unreduced dislocation of the mandibular joint following eclampsia: report of a
      surgically treated case.

PMID- 15440070
TI  - Case report of sciatic pains relieved by the removal of a radicular cyst from the
      maxilla.

PMID- 15440071
TI  - Surgical repair of alveolar depression in the anterior segment by mucoperiosteal
      onlay; report of a case.

PMID- 15440072
TI  - Endothelial myeloma; report of a case.

PMID- 15440073
TI  - Bilateral odontoma; report of a case.

PMID- 15440074
TI  - A newly observed ophthalmologic occupational hazard in dentistry.

PMID- 15440075
TI  - The treatment of ulceromembranous stomatitis with penicillin chewing troches.

PMID- 15440076
TI  - Evaluation of patients for oral surgery.

PMID- 15440077
TI  - Significance of correct processing in intraoral roentgenography.

PMID- 15440078
TI  - The use of penicillin-streptomycin in the treatment of infected pulpless teeth.

PMID- 15440079
TI  - Salivary bacteria; a study of two methods for counting Lactobacillus acidophilus
      in saliva.

PMID- 15440080
TI  - [Retropubic prostatectomy].

PMID- 15440081
TI  - [Pancreatic secretory function; production of enzyme in healthy children and
      comparison of the various methods of estimation].

PMID- 15440082
TI  - [Effect of menstruation urine and blood-serum upon human spermatozoa].

PMID- 15440083
TI  - [Experience with peridural anesthetization].

PMID- 15440084
TI  - [Surgical aspect of disease of the stomach].

PMID- 15440085
TI  - [Fractures of the skull; report of 156 cases].

PMID- 15440086
TI  - [Effective treatment of erosion of the portio with azulenol ointment].

PMID- 15440087
TI  - [Mass poisoning caused by bread made with ergotized flour].

PMID- 15440088
TI  - [Contribution to the history of retropubic prostatectomy].

PMID- 15440089
TI  - [Primary sarcoma of the vagina in the second half of pregnancy].

PMID- 15440090
TI  - [Apoplexy and gastric ulcer].

PMID- 15440091
TI  - [New method in diagnosis of hypophyseal and adrenocortical insufficiency].

PMID- 15440092
TI  - [Clearance values of the separate kidneys].

PMID- 15440093
TI  - [Effect of caffeine in hypertension].

PMID- 15440094
TI  - [Comparative statistics (1941 and 1948) on the healing of surgical wounds of the
      urinary system].

PMID- 15440095
TI  - [Histology of the central nervous system in experimental poisoning with barium
      chloride].

PMID- 15440096
TI  - [Chronic enteritis].

PMID- 15440097
TI  - [Nutrition by means of a jejunal tube].

PMID- 15440098
TI  - [Recent experimental developments in histology; optical analysis by means of the
      polarization microscope].

PMID- 15440099
TI  - [Simple apparatus for blood-transfusion and intravenous infusion].

PMID- 15440100
TI  - [Fibroma of the rhinopharynx originating from the Eustachian tube].

PMID- 15440101
TI  - [Ewing sarcoma of the thigh].

PMID- 15440102
TI  - [Experimental lesions of the pancreas; effect of defective diets and of
      poisoning].

PMID- 15440103
TI  - [Pathogenesis of sulfonamide poisoning and to the treatment of subsequent
      myopia].

PMID- 15440104
TI  - [Dimercaptopropanol (BAL, Dicaptol); its efficacy in experimental poisoning with
      thallium].

PMID- 15440105
TI  - [New serological test, with special reference to early diagnosis of endocarditis
      lenta and to the therapeutic evaluation of the effect of administered
      antibiotics].

PMID- 15440106
TI  - [Effect of physical work upon the opsonin index of serum].

PMID- 15440107
TI  - [Prevention of headache following lumbar puncture].

PMID- 15440108
TI  - [Indications for pneumoperitoneum in treatment of tuberculosis].

PMID- 15440109
TI  - [Dislocations in the pelvic girdle].

PMID- 15440110
TI  - [Atypical course of chloroleukemia].

PMID- 15440111
TI  - [Calcification in the spleen associated with abdominal disseminated calcareous
      deposits].

PMID- 15440112
TI  - [Hydronephrosis and tuberculosis of the same kidney].

PMID- 15440113
TI  - [Cystic formations of the bone].

PMID- 15440114
TI  - [Primary malignant tumor of the upper left lobe of the lung; left pneumectomy].

PMID- 15440115
TI  - [Subarachnoid hemorrhage with profuse hemorrhage of the vitreous].

PMID- 15440116
TI  - [A simple apparatus for transfusion].

PMID- 15440117
TI  - [Titration of hepatic extracts].

PMID- 15440118
TI  - [Therapeutic action of thymus extract in Werlhof's disease].

PMID- 15440119
TI  - [Evolution of H and O antibodies after electroshock].

PMID- 15440120
TI  - [The absorption of iron in gastrectomized patients].

PMID- 15440121
TI  - [Normal values of bilirubinemia].

PMID- 15440122
TI  - [Experimental study on bilateral apoplexy of the adrenals; Waterhouse
      Friderichsen syndrome].

PMID- 15440123
TI  - [Comparative anatomo-histopathological and radiological study of the
      interureteric ridge].

PMID- 15440124
TI  - [Technic, indications and results of serial pyelography; its relation to
      urography].

PMID- 15440125
TI  - [Problems of geriatrics].

PMID- 15440126
TI  - [Observations on streptomycin therapy of tuberculous meningitis and of miliary
      tuberculosis].

PMID- 15440127
TI  - [Contribution to the study of tocopherolemia in some normal and pathological
      conditions].

PMID- 15440128
TI  - [Erythrophagocytosis in circulating blood].

PMID- 15440129
TI  - [Contribution to the study of the polycystic pancreas].

PMID- 15440130
TI  - [Importance of lipids in the pathogenesis of arteriosclerosis].

PMID- 15440131
TI  - [Ocular diseases characteristic of premature infants].

PMID- 15440132
TI  - [Not Available].

PMID- 15440133
TI  - The treatment of pernicious anaemia.

PMID- 15440134
TI  - Variations of the vitamin H level in mothers milk during a period of twelve
      months (September 1948-August 1949).

PMID- 15440135
TI  - Epidemic diarrhea of the newborn.

PMID- 15440136
TI  - [Neuro-psychic disorders as sequels of infantile pneumonia and broncho
      pneumonia].

PMID- 15440137
TI  - [Tick neurosis in children].

PMID- 15440138
TI  - [Treatment of Moussous' erythroderma desquamativum with desoxycorticosterone
      acetate and potassium].

PMID- 15440139
TI  - [Significance of albumino-cytologic dissociation].

PMID- 15440140
TI  - [Behaviour of circulating reserve protein in the blood following ingestion of
      various protein foods].

PMID- 15440141
TI  - [Abdominal anaphylactoid purpura in an infant].

PMID- 15440142
TI  - [Colloid curves in suppurative meningitis treated with penicillin].

PMID- 15440143
TI  - [Commemorative meeting dedicated to the memory of Maurice Roy].

PMID- 15440144
TI  - The first steps of the International ARPA and of the French ARPA.

PMID- 15440145
TI  - [Parodontal disease in pre- and post-puberal diabetes].

PMID- 15440146
TI  - [Parodontal disease and heredity].

PMID- 15440147
TI  - The influence of diseases of the thyroid gland upon the endodontium and the
      parodontium.

PMID- 15440148
TI  - [Senescence of the dentition].

PMID- 15440149
TI  - [The Geneva Convention of August 12, 1949 concerning the treatment of prisoners
      of war].

PMID- 15440150
TI  - [Modern treatment of tuberculous meningitis; complications and tests of cure].

PMID- 15440151
TI  - [Limits of exchange transfusions; failure of exchange transfusion during anuria
      secondary to malignant ictero-hemorrhagic spirochetosis].

PMID- 15440152
TI  - [General theory of pain].

PMID- 15440153
TI  - [Digestive pathology in 1950; intestinal amebiasis].

PMID- 15440154
TI  - [Physio-pathology of gastric pain].

PMID- 15440155
TI  - [Not Available].

PMID- 15440156
TI  - [The Geneva Conventions of August 12, 1949; the task which remains].

PMID- 15440157
TI  - [Meningitis due to Salmonella].

PMID- 15440158
TI  - [Blood pressure during the Morgagni-Morel syndrome; biometric and statistical
      data].

PMID- 15440159
TI  - [First results of treatment of psoriasis by undecylenic acid].

PMID- 15440160
TI  - [Six new cases of the Klippel-Feil syndrome].

PMID- 15440161
TI  - [Thermotherapy of intestinal amebiasis].

PMID- 15440162
TI  - [In search of a law of continuity].

PMID- 15440163
TI  - [The variations of lipemia in prolonged infectious jaundice; importance of
      phospholipids].

PMID- 15440164
TI  - [Possibilities, indications and results of hepatectomy in tumors of the liver].

PMID- 15440165
TI  - [Tuberculosis of the lymph nodes of the hepatic pedicle].

PMID- 15440166
TI  - [In search of a law of continuity].

PMID- 15440167
TI  - [Amenorrhea and acute infectious jaundice with nodular hepatitis].

PMID- 15440168
TI  - [Massive albuminuria in rheumatic purpura with enlarged spleen].

PMID- 15440169
TI  - [Treatment of lipoid nephrosis].

PMID- 15440170
TI  - [Betrothal mythomania].

PMID- 15440171
TI  - [Utero-ovarian dysendocrinia and pulmonary tuberculosis in women].

PMID- 15440172
TI  - [Functional prognosis of the parotitic orchitis; unilateral orchitis followed by
      the transitory azoospermia].

PMID- 15440173
TI  - [In search of a law of continuity].

PMID- 15440174
TI  - [Has hystero-traumatism disappeared?].

PMID- 15440176
TI  - [Vaquez'-disease and chorea].

PMID- 15440175
TI  - [Leukocytosis and lymphocytosis in whooping cough; modern treatment of whooping
      cough (vaccine, serum, streptomycin)].

PMID- 15440177
TI  - [Adrenocorticotropic hormone in the treatment of asthma].

PMID- 15440178
TI  - [Relative hemianesthesia].

PMID- 15440179
TI  - [Changing moods; cyclothymia].

PMID- 15440180
TI  - [Cervical aberrant lateral thyroids].

PMID- 15440181
TI  - [Streptomycin in treatment of simple and grave dyspepsia in infants].

PMID- 15440182
TI  - [Not Available].

PMID- 15440183
TI  - [The revival of alcoholic peril and the efforts of the medical corps].

PMID- 15440184
TI  - [The diseases of the blood in 1950].

PMID- 15440186
TI  - [Neutropenia of splenic origin and hypersplenia].

PMID- 15440185
TI  - [Myeloid splenomegaly in adults].

PMID- 15440187
TI  - [Actual treatment of malignant blood diseases].

PMID- 15440188
TI  - [Not Available].

PMID- 15440189
TI  - [First clinical results with eutocine, a natural factor in uterine contraction in
      labor].

PMID- 15440190
TI  - [Application of BCG serum in schools].

PMID- 15440191
TI  - [Pulmonary emphysema; clinical, spirographic and bronchometric study].

PMID- 15440192
TI  - [Use of streptomycin in treatment of Addison's disease].

PMID- 15440193
TI  - [Diabetes in acromegaly; 3 personal cases].

PMID- 15440194
TI  - [Postmenopausal Basedow syndrome cured with estrogens; changes observed in the
      extracellular fluids].

PMID- 15440195
TI  - [Serofibrinous pleurisy indicating bronchial dilatation].

PMID- 15440196
TI  - [Treatment of bronchial cancer].

PMID- 15440197
TI  - [Treatment of postpartum venous infections with aureomycin and heparin retarded
      action].

PMID- 15440198
TI  - [Coronary vasodilatation, cause of angina pectoris].

PMID- 15440199
TI  - [Acute hemolytic anemia].

PMID- 15440200
TI  - [Scrub typhus in Indochina and its treatment with chloromycetin].

PMID- 15440201
TI  - [Prolonged heparine].

PMID- 15440202
TI  - [Ultrasonics Congress at Erlangen, May 1949].

PMID- 15440203
TI  - [Fractures of the neck of the femur following roentgen therapy of cancer of the
      uterus].

PMID- 15440204
TI  - [Angiocardiography; technic and indications].

PMID- 15440205
TI  - [Mesenterium commune; its radiologic diagnosis and symptomatology].

PMID- 15440206
TI  - [Not Available].

PMID- 15440207
TI  - [Infectious diseases in 1950].

PMID- 15440208
TI  - [Associated antibiotic therapy in typhoid fever].

PMID- 15440209
TI  - [Practical data on preventive vaccination].

PMID- 15440210
TI  - [Scarlatina and tuberculous serofibrinous pleurisy; a case].

PMID- 15440211
TI  - [Action of desoxycorticosterone acetate on the biochemistry of the blood in
      certain infectious diseases].

PMID- 15440213
TI  - [Aureomycin and chloromycetin in the treatment of whooping cough].

PMID- 15440212
TI  - [Iron in the blood in leishmaniasis].

PMID- 15440214
TI  - [Hemolytic manifestations and hematomedullary examinations in Sardinian children
      during PAS therapy].

PMID- 15440216
TI  - [Disease of the liver in an infant whose mother developed infectious hepatitis
      during pregnancy; anatomoclinical study].

PMID- 15440215
TI  - [The therapeutic combination of penicillin and synthetic antihistamines in
      glomerulonephritis in children].

PMID- 15440217
TI  - [Congenital lacuna of the parietal bones and nevus pigmentosus and partial
      alopecia].

PMID- 15440218
TI  - [Atelectasis in infants].

PMID- 15440219
TI  - [Pathogenesis and therapy of dysenteric syndromes in infants].

PMID- 15440220
TI  - [Homage to the memory of Rocco Jemma].

PMID- 15440221
TI  - [Auxology; factors of growth].

PMID- 15440222
TI  - [Present therapy of tuberculous meningitis in children].

PMID- 15440223
TI  - [Typhoid and salmonellosis in infants].

PMID- 15440224
TI  - [Variations of the glutathione level in the cerebrospinal fluid in tuberculous
      meningitis treated with streptomycin].

PMID- 15440225
TI  - [Seven years' experience with intramedullary (intra-iliac) blood transfusion].

PMID- 15440226
TI  - [pH value of breast milk].

PMID- 15440227
TI  - [Toxoplasmosis; a case of meningoencephalitis caused by a Toxoplasma].

PMID- 15440228
TI  - [Case of latent infantile psychomotor epilepsy studied
      electroencephalographically and submitted to treatment with zeta(+) glutamic acid
      and diphenylhydantoin].

PMID- 15440229
TI  - [New treatments in poliomyelitis].

PMID- 15440230
TI  - [Toxoplasmosis in chickens].

PMID- 15440231
TI  - [Biochemotherapy in typhoid-paratyphoid infections].

PMID- 15440232
TI  - [Streptomycin therapy of tuberculous meningitis].

PMID- 15440233
TI  - [Influenza; biology and viability of the virus].

PMID- 15440234
TI  - [Influenza in children].

PMID- 15440235
TI  - [Factors predisposing the organism to fatal pneumonia in infants].

PMID- 15440236
TI  - [Treatment of acute pleural empyemas in children].

PMID- 15440237
TI  - [Electroencephalography in pediatrics].

PMID- 15440238
TI  - [Serology of congenital syphilis].

PMID- 15440239
TI  - [Effect of fresh and preserved tissue on the course of certain surgical diseases
      in children; observations of 26 cases].

PMID- 15440240
TI  - [Case of malaria in the first weeks of life].

PMID- 15440241
TI  - [Case of malaria in first weeks of the life].

PMID- 15440242
TI  - [Case of suppurative infection of the paranephritic tissue of unusual etiology in
      a child].

PMID- 15440243
TI  - [Use of streptomycin in non-tuberculous infections].

PMID- 15440244
TI  - [Primary, non-specific pneumonia of viral origin].

PMID- 15440245
TI  - [Time of discharge of ocarlet fever patients from hospitals].

PMID- 15440246
TI  - [Organization in prevention of rickets].

PMID- 15440247
TI  - [Organization of mobile units within the Provincial Maternal Consultation and
      Child Welfare Organizations].

PMID- 15440248
TI  - [Subsidy for the clinical and statistical study of early congenital syphilis].

PMID- 15440250
TI  - [Obstetric diseases of the newborn].

PMID- 15440249
TI  - [Tetanus neonatorum; 27 cases].

PMID- 15440251
TI  - [BCG immunization].

PMID- 15440252
TI  - [78 Cases of dyspepsia and toxicosis treated by hydration by the intravenous drip
      method].

PMID- 15440253
TI  - [Importance of Rh factor in pediatrics].

PMID- 15440255
TI  - [6th International Congress on Pediatrics, Zurich, 1950].

PMID- 15440254
TI  - [2 Cases of erythroblastosis treated by exchange transfusion].

PMID- 15440256
TI  - [Diagnosis of rheumatic diseases in children].

PMID- 15440257
TI  - [Treatment of alimentary toxicosis by means of subcutaneous infusions].

PMID- 15440258
TI  - [Classification of vaginal discharges in infants and children].

PMID- 15440259
TI  - [Gonorrhea in childhood].

PMID- 15440260
TI  - [Foreign bodies in the vagina in children].

PMID- 15440261
TI  - [Infectious vaginal discharge in children caused by Streptococcus beta
      haemolyticus].

PMID- 15440262
TI  - [Vaginal discharge at the age of puberty].

PMID- 15440263
TI  - [Treatment of vaginal discharges in childhood].

PMID- 15440264
TI  - [Vaginal discharges in childhood treated with penicillin].

PMID- 15440266
TI  - [So called complications following BCG vaccination].

PMID- 15440265
TI  - [Some remarks on so called BCG vaccination complications].

PMID- 15440267
TI  - [Report of BCG vaccination in the region of Hradec].

PMID- 15440268
TI  - [Case of deep ulcer following BCG vaccination].

PMID- 15440269
TI  - [Fulminating meningococcus septicemia; Waterhouse-Friderichsen syndrome].

PMID- 15440270
TI  - [Case of ectromelia].

PMID- 15440271
TI  - [Penicillin in the diagnosis of acute abdominal conditions].

PMID- 15440272
TI  - [Treatment of pneumococcic meningitis in children].

PMID- 15440274
TI  - [Detailed clinical analysis of Niemann-Pick's disease in a 14 months old infant].

PMID- 15440273
TI  - [Certain aspects in the microsedimentation in newborn and premature].

PMID- 15440275
TI  - [Renal tumor in children].

PMID- 15440276
TI  - [Malaria in children].

PMID- 15440277
TI  - [Unification of mental and physical care of children].

PMID- 15440278
TI  - [Age characteristics in the course of malarial infection in different age
      groups].

PMID- 15440279
TI  - [Clinical aspect of congenital malaria].

PMID- 15440280
TI  - [Fulminant tertian malaria in children].

PMID- 15440281
TI  - [Malaria in infants and young children following blood transfusion].

PMID- 15440282
TI  - [Early diagnosis and manifestations of tuberculous meningitis].

PMID- 15440283
TI  - [Indications and efficacy of streptomycin therapy of tuberculosis in children].

PMID- 15440284
TI  - [Respiratory age characteristics in children with tuberculous meningitis].

PMID- 15440285
TI  - [Catamnestic data on the psychic state of children following tuberculous
      meningitis treated with streptomycin].

PMID- 15440286
TI  - [Tuberculous bronchadenitis simulating diphtherial croup in children].

PMID- 15440287
TI  - [Modifications of the myocardium in experimental tuberculosis].

PMID- 15440288
TI  - [Follow up data on physical development of infants].

PMID- 15440289
TI  - [Modification of Kernig's sign in early childhood].

PMID- 15440290
TI  - [Case of acute tuberculous sepsis in boy of nine and half years of age].

PMID- 15440292
TI  - An appraisal of some analgesic agents and methods.

PMID- 15440291
TI  - [N. I. Lunin (70 years since his outstanding discovery on the significance of
      nonorganic salts in nutrition of animals].

PMID- 15440293
TI  - Reconstruction of the common bile duct.

PMID- 15440295
TI  - Toxemias of pregnancy.

PMID- 15440294
TI  - Recent advances in the surgical treatment of carcinoma of the esophagus; a
      discussion of cervical esophagogastrostomy.

PMID- 15440296
TI  - [Morphine and substitutes].

PMID- 15440297
TI  - [Para-aminosalicylic acid].

PMID- 15440298
TI  - [In memoriam; J.A.J. Vergroesen].

PMID- 15440299
TI  - [Anticoagulants].

PMID- 15440300
TI  - [Chemistry of streptomycin].

PMID- 15440301
TI  - [Chemistry of p-aminosalicylic acid].

PMID- 15440302
TI  - [Changes in the blood picture following use of medications].

PMID- 15440303
TI  - [Rutin as simulant of vitamin P].

PMID- 15440304
TI  - [Chemotherapeutic examination of protozoacides].

PMID- 15440305
TI  - [Certain acids and glycerides of cod liver oil].

PMID- 15440307
TI  - [Biotin].

PMID- 15440306
TI  - [Lithium aluminum hydride in organic chemistry].

PMID- 15440308
TI  - [Antibiotics other than penicillin; antibiotics from fungi, Fusaria and
      Aspergilla].

PMID- 15440309
TI  - [Cocaism in South America].

PMID- 15440310
TI  - [Insecticidal effect of thiodiphenylamine and its use in anopheles control].

PMID- 15440311
TI  - [Vapor pressure of technical tricresyl phosphate].

PMID- 15440312
TI  - [Cardiac glucosides of the digitalis group].

PMID- 15440313
TI  - [The Peruvian balsam; parent stock, original habitat and present occurrence,
      indigenous names, classification].

PMID- 15440314
TI  - [Substances contained in Arnica; organic acids, carbohydrates and tannins of
      arnica root].

PMID- 15440315
TI  - [Effect of storage upon the volatile oil content of plants fed different
      fertilizers].

PMID- 15440316
TI  - [Experiments with preparations of raw vegetable matter; comparative study of agar
      and gelar].

PMID- 15440317
TI  - [Signatures in medicine and chemistry].

PMID- 15440318
TI  - [Arrow poisons and their therapeutic significance].

PMID- 15440319
TI  - [Johann Wolfgang Dobereiner (1780-1849)].

PMID- 15440320
TI  - The desoxyribose nucleic acid content of animal nuclei.

PMID- 15440321
TI  - The resistance of cell membranes to internal pressure.

PMID- 15440322
TI  - Changes in the distribution of nitrogen during starvation in the grasshopper,
      Chortophaga viridifasciata De Geer.

PMID- 15440323
TI  - Synthesis of vitamins of the B-complex by Chilomonas paramecium.

PMID- 15440324
TI  - Water and solid content of endocrine organs of rats following prolonged
      injections of testosterone propionate.

PMID- 15440326
TI  - Observations on the reaction of Pelomyxa carolinensis subjected to a direct
      current electric field.

PMID- 15440325
TI  - Oxygen consumption of testes from adrenalectomized and normal rats after
      prolonged treatment with testosterone propionate.

PMID- 15440327
TI  - The modification of developmental patterns in the sand dollar with sodium azide.

PMID- 15440328
TI  - The modification of developmental patterns in the sand dollar by thiourea.

PMID- 15440329
TI  - Heating rate and heat-shortening temperature in Eisenia foetida (Savigny).

PMID- 15440330
TI  - The comparative hypoxic resistance of hibernators and nonhibernators.

PMID- 15440332
TI  - Mammaplasty; the one-stage transposition operation.

PMID- 15440331
TI  - Some half forgotten chapters in the development of plastic surgery.

PMID- 15440333
TI  - The late treatment of burns.

PMID- 15440334
TI  - Reconstruction of scrotum and skin of penis.

PMID- 15440336
TI  - Obliteration of scars by shaving.

PMID- 15440335
TI  - The use and therapeutic value of music in the hospital and operating room.

PMID- 15440337
TI  - Beryllium granuloma of the nose; a case report.

PMID- 15440338
TI  - Auto and homotransplantation of skin preserved at low temperature.

PMID- 15440339
TI  - [Phlebography (technic, indications, and results)].

PMID- 15440340
TI  - [Variations of the level of prothrombinemia after surgical operations].

PMID- 15440341
TI  - [Treatment of hematogenous osteomyelitis with intraarterial penicillin and stasis
      by Bier's method; clinical and bacteriological contribution].

PMID- 15440342
TI  - [Toluidine blue as an antiheparinic; pharmacological study].

PMID- 15440343
TI  - [Technic of arteriography].

PMID- 15440344
TI  - [Voluminous unilocular cystadenoma of the liver].

PMID- 15440345
TI  - [Progress in the treatment of acute appendicitis; casuistics of 5 years].

PMID- 15440346
TI  - [Anatomo-pathological and clinical aspects of 110 cases of goiter].

PMID- 15440347
TI  - [Importance of the gastric stasis fluids of the gastrectomized in the genesis of
      postoperative complications; clinical and experimental observations, with
      research on the behavior of intestinal absorption in the postoperative period].

PMID- 15440348
TI  - [Primary tumors of the lung].

PMID- 15440349
TI  - [Function tests of the bone marrow and blood plasma in infectious hepatitis].

PMID- 15440350
TI  - [Genesis of erythrocytic anomalies in the Rietti-Greppi-Micheli syndrome].

PMID- 15440352
TI  - [General adaptation syndrome and adaptation disease].

PMID- 15440351
TI  - [Peculiar phenomena of the plasma in leukemia].

PMID- 15440353
TI  - [Lichteim type of pernicious anemia treated with vitamin B 12].

PMID- 15440355
TI  - [Importance of peritoneal drainage in the treatment of the gravest forms of acute
      appendicitis].

PMID- 15440354
TI  - [The treatment of arthropathy with combined injections of desoxycorticosterone
      and ascorbic acid (method of Lewin and Wassen) personal experience].

PMID- 15440356
TI  - [Thoracoplasty by axillary route with resection of 7 ribs in one operation].

PMID- 15440357
TI  - [Rabies vaccination].

PMID- 15440358
TI  - [Results of the use of vitamin B12 in a case of funicular myelosis].

PMID- 15440359
TI  - [Central and peripheral hematological modifications in the course of treatment
      with streptomycin and p-aminosalicylic acid].

PMID- 15440360
TI  - [Funiculo-hernial strangulation].

PMID- 15440362
TI  - [Thinking machines].

PMID- 15440361
TI  - [Regional ileitis].

PMID- 15440363
TI  - [Present criteria for the diagnosis of arteritis].

PMID- 15440364
TI  - [Index of erythrocyte sphericity in normal conditions and in some blood
      diseases].

PMID- 15440366
TI  - [Determination of sex at will].

PMID- 15440365
TI  - [Treatment of tetanus].

PMID- 15440367
TI  - [Endobronchial antibiotics in the treatment of bronchiectasis].

PMID- 15440368
TI  - [Local treatment of empyema with streptomycin].

PMID- 15440369
TI  - [First observations on ligation of the inferior cava in the treatment of cardiac
      insufficiency].

PMID- 15440370
TI  - [Erythrocytometric studies in constitutional microcytic anemia].

PMID- 15440371
TI  - [Treatment of hyperhidrosis].

PMID- 15440372
TI  - [The error of a recent American experiment will reinforce another old error on
      the genesis of peptic ulcer].

PMID- 15440373
TI  - [The influence of the surrounding temperature in human life].

PMID- 15440374
TI  - [Pathogenetic interpretation of the acute pulmonary edema of high blood
      pressure].

PMID- 15440375
TI  - [Medical therapy of the cutaneous sequels of irradiation].

PMID- 15440376
TI  - [Roentgen therapy of the hydrocephalus which accompanies tuberculous meningitis
      treated with streptomycin].

PMID- 15440377
TI  - [Familial blood diseases with substrata of microcythemia and sickle cell anemia].

PMID- 15440378
TI  - [Purpura haemorrhagica due to ingestion of dimethine (dimethylamino
      ethylbenzylamidine)].

PMID- 15440379
TI  - [Pulmonary abscess in severe diabetes cured by aerosol penicillin and insulin
      therapy].

PMID- 15440380
TI  - [Observations on blood donors after repeated donations].

PMID- 15440381
TI  - [8 Cases of inguinal appendicocele].

PMID- 15440382
TI  - [Modifications of the Bassini process].

PMID- 15440383
TI  - [Andrea Belli's "Dizionario del Segretista"].

PMID- 15440384
TI  - [Choleperitoneum due to perforation of a calculous gallbladder].

PMID- 15440385
TI  - [6 Cases of typhoid-para-typhoid infection treated with chloromycetin].

PMID- 15440386
TI  - [2d National Congress on Antibiotics].

PMID- 15440387
TI  - [Rapid microreactions for diagnosis of syphilis and their practical application
      in communal venereal disease dispensaries].

PMID- 15440389
TI  - [Biliary syndromes caused by pathology of the common bile duct and Vater's
      ampulla].

PMID- 15440388
TI  - [Treatment of hyperthyroid conditions with Levico-Vetriolo ferruginous-arsenical
      water].

PMID- 15440390
TI  - [Small anastomoses in the gastrojejunostomy of gastrectomy; clinico-statistical
      study].

PMID- 15440391
TI  - [Primary carcinoma of the hepatic duct; resection followed by
      hepaticoduodenostomy].

PMID- 15440392
TI  - [Useful application of the Delbet apparatus].

PMID- 15440393
TI  - [Does arable land still exist which can be used?].

PMID- 15440394
TI  - [Venous thrombosis and treatment with anticoagulants].

PMID- 15440395
TI  - [Encephalitis and streptomycin in relation to grippe].

PMID- 15440396
TI  - [The duodenum is the most important organ in the vegetative life of the
      individual].

PMID- 15440397
TI  - [Primary treatment of gunshot wounds of the extremities].

PMID- 15440398
TI  - [Primary cancer of the gallbladder and calculous cholecystitis].

PMID- 15440399
TI  - [Disadvantages of overdoses of desoxycorticosterone acetate in rheumatoid
      arthritis].

PMID- 15440400
TI  - [Selye's theory on general syndrome of adaptation and adaptation disease].

PMID- 15440401
TI  - [Virusology as a problem of public health].

PMID- 15440402
TI  - [Evolution of the hand].

PMID- 15440403
TI  - [Tularemia].

PMID- 15440404
TI  - [Determination of sex in hermaphroditism].

PMID- 15440405
TI  - [Case of thallium poisoning treated with BAL].

PMID- 15440406
TI  - [Effect of electric shock therapy on the morphology of circulatory blood].

PMID- 15440407
TI  - [Severe acute uremia with convulsions following allergy to sulfonamides].

PMID- 15440409
TI  - [Modern treatment of epilepsy with electroencephalographic control of the
      disease].

PMID- 15440408
TI  - [Selye's theory on the general adaptation syndrome and adaptation disease].

PMID- 15440410
TI  - [A contribution to the study of correlation of chickenpox and herpes zoster].

PMID- 15440411
TI  - [A case of thallium poisoning treated with BAL].

PMID- 15440412
TI  - [Use of streptomycin in surgery].

PMID- 15440413
TI  - [Tularemia; symptoms and clinical course].

PMID- 15440414
TI  - [Further investigations on preventing abortions by antistine].

PMID- 15440415
TI  - [Angina pectoris in acute chronic anemia].

PMID- 15440416
TI  - [Electrocardiography in neurosis of the circulatory system].

PMID- 15440417
TI  - [Problems concerning blood groups and blood transfusion].

PMID- 15440419
TI  - [Tularemia].

PMID- 15440418
TI  - [Streptomycin and its use in surgery].

PMID- 15440420
TI  - [About the need for teaching physico-therapy in the medical schools in Poland].

PMID- 15440421
TI  - [Spondylitis ankylopoetica (radiology)].

PMID- 15440422
TI  - [Spondylitis ankylopoetica (Perispondylitis ankylosans)].

PMID- 15440423
TI  - [Good anesthesia and a good anesthetist].

PMID- 15440424
TI  - [Gunshot injuries during the war and post-war years from the view point of
      forensic medicine observations].

PMID- 15440425
TI  - [Value of streptomycin in therapy of surgical tuberculosis].

PMID- 15440426
TI  - [Plummer-Vinson syndrome with co-existing Recklinghausen's disease].

PMID- 15440427
TI  - [Electrocardiographic examination in neuritis of the circulatory system].

PMID- 15440429
TI  - [Biological methods in diagnosis of cancer].

PMID- 15440428
TI  - [Problems concerning blood grouping and blood transfusion therapy].

PMID- 15440430
TI  - [Streptomycin and its use in surgery].

PMID- 15440431
TI  - [Necessity for teaching physical therapy in medical departments in Poland].

PMID- 15440432
TI  - [Rheumatism in school-age children].

PMID- 15440433
TI  - [Occurrence of rheumatism among the population of the coast].

PMID- 15440434
TI  - [Surgical treatment in pulmonary tuberculosis].

PMID- 15440435
TI  - [Medico-legal aspects of gun-shot wounds during the war and post-war periods].

PMID- 15440437
TI  - [Surgical treatment of varicose veins; phlebography].

PMID- 15440436
TI  - [Postoperative gastric drainage].

PMID- 15440439
TI  - [Biological methods in diagnosis of cancer].

PMID- 15440438
TI  - [Labyrinthine reactions in children treated with streptomycin].

PMID- 15440440
TI  - [Use of streptomycin in surgery].

PMID- 15440441
TI  - [The necessity of teaching physical medicine in medical schools in Poland].

PMID- 15440442
TI  - [Not Available].

PMID- 15440443
TI  - [Urine incontinence in women].

PMID- 15440444
TI  - [Observation on the administration of vitamin K in hemophilia].

PMID- 15440445
TI  - [Frequency of abortions].

PMID- 15440446
TI  - [Primary cancer of the liver with clinical symptoms of an abscess].

PMID- 15440447
TI  - [Case of stab wound of the heart].

PMID- 15440448
TI  - [Enzymatologic aspects of the mechanism of action of sulfonamides and
      antibiotics].

PMID- 15440449
TI  - [The necessity of teaching physical medicine in medical schools in Poland].

PMID- 15440450
TI  - [Difference of opinions regarding rheumatism].

PMID- 15440451
TI  - [Role of the nervous system in relation to peptic ulcer; studies in Soviet
      Union].

PMID- 15440452
TI  - [Treatment of rheumatism with steroid hormones and ascorbic acid].

PMID- 15440453
TI  - [Novocaine treatment of diseases of the peripheral arteries].

PMID- 15440454
TI  - [Preliminary investigations on contemporary technic of dosage of x-rays in
      treatment of cancer].

PMID- 15440455
TI  - [A case of mediastinal neurilemmoma].

PMID- 15440456
TI  - [Case of Recklinghausen's disease with extensive invasion of the central nervous
      system cured with x-rays].

PMID- 15440457
TI  - [Mechanism of action of sulfonamides and antibiotics in the light of enzymology].

PMID- 15440458
TI  - [The need of teaching of physical medicine in medical schools in Poland].

PMID- 15440459
TI  - Streptokinase; 'streptococcal enzymatic debridement'.

PMID- 15440460
TI  - Explosions in the operating theatre.

PMID- 15440462
TI  - Primary or essential hyperidrosis.

PMID- 15440461
TI  - Aureomycin.

PMID- 15440463
TI  - The investigation and treatment of anogenital pruritus.

PMID- 15440464
TI  - Neuro-ophthalmology.

PMID- 15440465
TI  - CLINICO-PATHOLOGICAL conference; retinal and renal lesions in a case of diabetes.

PMID- 15440466
TI  - The physiology of growth.

PMID- 15440467
TI  - The surgery of the adrenal glands.

PMID- 15440468
TI  - Intermittent claudication; a review.

PMID- 15440469
TI  - Recent advances in the treatment of rheumatoid arthritis.

PMID- 15440470
TI  - Carcinoma of undescended testis.

PMID- 15440471
TI  - Repair of tendon injuries in the hand with special reference to flexor tendons.

PMID- 15440472
TI  - Periodic fever and periodic abdominalgia.

PMID- 15440473
TI  - The management of ulcerative colitis.

PMID- 15440475
TI  - The liver-kidney factor in unexpected surgical deaths.

PMID- 15440474
TI  - Diagnosis and treatment of segmental neuralgia.

PMID- 15440476
TI  - Cortisone.

PMID- 15440477
TI  - Management of hay fever.

PMID- 15440478
TI  - Management of allergic dermatitis.

PMID- 15440479
TI  - Treatment of bronchial asthma.

PMID- 15440480
TI  - Intrinsic asthma.

PMID- 15440481
TI  - Progress in anesthesiology.

PMID- 15440482
TI  - The hypersensitive carotid sinus.

PMID- 15440483
TI  - Common problems in coronary artery disease.

PMID- 15440484
TI  - Carcinoma of the upper rectum and rectosigmoid; clinical report on high inferior
      mesenteric ligation.

PMID- 15440485
TI  - Practical applications of bacteriologic studies in the diagnosis of infectious
      diseases.

PMID- 15440486
TI  - Diagnosis and treatment of acute pancreatic disease.

PMID- 15440487
TI  - Some problems presented by cranial defects.

PMID- 15440488
TI  - Splenectomy in leukemia.

PMID- 15440489
TI  - Meckel's diverticulum as the source of massive intestinal hemorrhage.

PMID- 15440490
TI  - Pulmonary function studies in surgery.

PMID- 15440491
TI  - Polyps of the large bowel.

PMID- 15440492
TI  - The modern treatment of rheumatoid arthritis.

PMID- 15440493
TI  - Hemophilia simulating acute surgical abdomen.

PMID- 15440494
TI  - Management of prostatitis.

PMID- 15440495
TI  - Treatment of the common cold.

PMID- 15440497
TI  - [Classification of bronchitis and bronchiectasis and the role of bronchoscopic
      films].

PMID- 15440496
TI  - [Radiological and clinical study of infiltrative diffuse hematogenic
      tuberculosis].

PMID- 15440498
TI  - [Two cases of pulmonary suppurations with pyosclerosis treated by extrapleural
      pneumothorax].

PMID- 15440499
TI  - [Technic of surgical pneumolysis of the base].

PMID- 15440500
TI  - [Two special cases of esophagectomy].

PMID- 15440501
TI  - [Secondary closing of cavities after speleotomy; utilization of placental
      fragments as filling material].

PMID- 15440502
TI  - [Encysted pleuro-pulmonary hematomas].

PMID- 15440503
TI  - [Case of isolated tracheobronchial tuberculosis].

PMID- 15440504
TI  - [Complementary surgery of intrapleural pneumothorax; its indications, results,
      and place in relation to substitution surgery].

PMID- 15440506
TI  - [Treatment of purulent tuberculous pleurisy by provoked adhesions].

PMID- 15440505
TI  - [Precocious adhesions following pneumolysis].

PMID- 15440507
TI  - The employment of elderly workers.

PMID- 15440508
TI  - The ageing heart.

PMID- 15440509
TI  - Pulmonary disease in the elderly.

PMID- 15440510
TI  - Skin disorders in the elderly.

PMID- 15440511
TI  - Genito-urinary disturbances in old age.

PMID- 15440512
TI  - Gynaecological problems of old age.

PMID- 15440513
TI  - Diet in old age.

PMID- 15440514
TI  - The facilities available for the care of the elderly in the home.

PMID- 15440515
TI  - Air embolism.

PMID- 15440516
TI  - The medical aspect of hair dyeing.

PMID- 15440517
TI  - Swiss sanatoria.

PMID- 15440518
TI  - Current therapeutics. XXXII. Vitamin K and its analogues.

PMID- 15440519
TI  - Vital statistics of tuberculosis in England and Wales.

PMID- 15440520
TI  - Some reflections on mass miniature radiography.

PMID- 15440521
TI  - The chemotherapy of tuberculosis.

PMID- 15440522
TI  - Tuberculosis of the skin.

PMID- 15440523
TI  - Tuberculosis of the genitourinary tract.

PMID- 15440524
TI  - The present status of surgery in pulmonary tuberculosis.

PMID- 15440525
TI  - Tuberculin and its application.

PMID- 15440526
TI  - Enuresis in childhood.

PMID- 15440527
TI  - Gastroduodenectomy.

PMID- 15440528
TI  - The corpse in Harley Street.

PMID- 15440529
TI  - Current therapeutics; the newer insulins.

PMID- 15440530
TI  - [Concept and significance of coincidental positive Wassermann].

PMID- 15440531
TI  - [Seropositivity and diagnosis of syphilis].

PMID- 15440532
TI  - [Human tapeworm infection].

PMID- 15440533
TI  - [Acute epipharyngitis or rhinopharyngitis in children].

PMID- 15440534
TI  - [Treatment of nocturnal enuresis].

PMID- 15440535
TI  - [New treatment of arthritis and neuralgia].

PMID- 15440536
TI  - [Use of cycliton in internal medicine].

PMID- 15440537
TI  - [Exeresis in pulmonary tuberculosis].

PMID- 15440538
TI  - [Use of thiotebesine in desperate cases of pulmonary tuberculosis].

PMID- 15440539
TI  - [Insufficiency of the adrenotropic factor of the pituitary as a cause of
      bronchial asthma, and pharmacological principle of the asthma remedy AM 49].

PMID- 15440540
TI  - [Practical experience with the asthma remedy AM 49].

PMID- 15440541
TI  - [Results of surgical therapy of otosclerosis].

PMID- 15440542
TI  - [Usual values of the cerebrospinal fluid and their interpretation].

PMID- 15440543
TI  - [Treatment of leukorrhea with a colloidal organic complex of a diphenylmethane
      acid derivative (negatol)].

PMID- 15440544
TI  - [Biliary dyskinesia; clinical, physiopathological and radiomanometric study].

PMID- 15440545
TI  - [Light, color and color-sense of the human eye; four stages in the development of
      a red-green blind painter; Goeth's color theory].

PMID- 15440546
TI  - [Treatment of disorders of peripheral circulation through medication of the
      autonomic nervous system; experience with hydergin and dilvasene].

PMID- 15440547
TI  - [Diaphyseal fractures of the forearm, 1930-1948, reviewed in 1949].

PMID- 15440548
TI  - [Methods of anesthesia to be used in our hospitals].

PMID- 15440549
TI  - [Clinical stomatology].

PMID- 15440550
TI  - [Irgafen in colibacillosis].

PMID- 15440551
TI  - [Development of pediatrics in Switzerland].

PMID- 15440552
TI  - [Clinical aspects of acute disturbances of water and electrolyte equilibrium in
      young children; toxicosis with hyperconcentration of electrolytes,
      hypopotassemia, and masked chloride deficiency in a 22 months old child].

PMID- 15440553
TI  - [Pyloric hypertrophy in an infant].

PMID- 15440554
TI  - [The corticotropic hypophyseal hormone, ACTH; an experimental and clinical
      study].

PMID- 15440555
TI  - [Clinical aspects and problems of polyradiculitis in children (Guillain-Barre
      syndrome].

PMID- 15440556
TI  - [Physiology of sucking in the newborn].

PMID- 15440557
TI  - [Disorders of dental development and their treatment in early childhood].

PMID- 15440558
TI  - [Dangers of phenacetin therapy in infancy].

PMID- 15440559
TI  - [Orthoptic therapy of strabismus in children].

PMID- 15440560
TI  - [New aspects of the diagnosis of chorea].

PMID- 15440561
TI  - [Bone and lymphnode metastases of uterine and prostatic cancer].

PMID- 15440562
TI  - [Hunger and appetite; nervous anorexia in children].

PMID- 15440563
TI  - [Practical significance of the Rh factor in blood transfusion].

PMID- 15440564
TI  - [Disorders of adaptation].

PMID- 15440565
TI  - [Fungous infections of the feet, with suggestions for therapy in general
      practice].

PMID- 15440566
TI  - [Present treatment of urinary infections].

PMID- 15440567
TI  - [Use of sulfonamides and penicillin in dermatology; clinical observations and
      results].

PMID- 15440568
TI  - [Present status of our knowledge of allergy and its practical application].

PMID- 15440569
TI  - [Compensation and decompensation in the spine].

PMID- 15440570
TI  - [Personal experiences with BCG vaccination].

PMID- 15440571
TI  - [Athletics and circulation; a review of the work of Ernst Jokl].

PMID- 15440572
TI  - [Hemoglobin as a problem in biology].

PMID- 15440573
TI  - [Problem of heredity in tuberculosis].

PMID- 15440574
TI  - [Neuropathologic viewpoints on ultrasonic therapy of arthroses and related
      conditions].

PMID- 15440575
TI  - [Polymorphic allergy due to sensitivity to milk and cheese; recurrent
      periarthritis of the shoulder; recurrent scintillating scotoma and cutaneous
      dystrophy of the skin of the fingers and toes].

PMID- 15440576
TI  - [Prostatic cancer; personal contribution to the technic; 21 total
      prostatectomies].

PMID- 15440577
TI  - [The cause of Cuvier's death; nosology of the Landry syndrome].

PMID- 15440578
TI  - [Dystocia due to large fetus].

PMID- 15440579
TI  - [Psychosensory disturbances in a case of encephalitic parkinsonism; peduncular
      hallucinosis].

PMID- 15440580
TI  - [Continuous peridural analgesia].

PMID- 15440581
TI  - [Ocular hypotension in glaucoma].

PMID- 15440582
TI  - [Irritable colon: contribution to its semiology].

PMID- 15440583
TI  - [Extrinsic stenosis of the duodenum].

PMID- 15440585
TI  - [Notes on a trip through the U.S.A..].

PMID- 15440584
TI  - [Campaign against tuberculosis in Norway].

PMID- 15440586
TI  - [Non-parasitic cysts, pseudocysts and effusions in serous cavities; excision
      exclusive of the inner layer; intracystic removal].

PMID- 15440587
TI  - [Chronic aorto-iliac thrombosis (Leriche syndrome); aortographic examination].

PMID- 15440588
TI  - [Treatment of alcoholism with antabuse (tetraethylthiuran disulfide); importance
      of the acetaldehyde].

PMID- 15440589
TI  - [Rhinorrhea; its surgical treatment].

PMID- 15440590
TI  - [Transverse presentation; 20 years' experience].

PMID- 15440591
TI  - [Complete course of allergic diseases presented at the Allergy Service of the
      Hospital Rivadavia; 7th conference: bronchopulmonary allergy manifestations].

PMID- 15440592
TI  - [Histaminic autohemotherapy].

PMID- 15440593
TI  - [Notes on a tour through the USA].

PMID- 15440594
TI  - [Surgical treatment of portal hypertension].

PMID- 15440595
TI  - [Severe hemorrhage due to diaphragmatic hernia; 4 cases].

PMID- 15440596
TI  - [Treatment of diseases of the peripheral arteries with tetraethylammonium
      chloride].

PMID- 15440597
TI  - [Antibiotics in obstetrics].

PMID- 15440598
TI  - [Diagnosis of intestinal amebiasis by curettage of the rectal mucosa].

PMID- 15440599
TI  - [Complete course of allergic diseases presented at the Allergy Service of the
      Hospital Rivadavaa; 8th conference; clinical forms of asthma].

PMID- 15440600
TI  - [Diabetes and old age].

PMID- 15440601
TI  - [Esophageal propagation of cancer of the stomach].

PMID- 15440602
TI  - [History of surgery of gastrointestinal cancer].

PMID- 15440604
TI  - [Notes on a tour through the U.S.A..].

PMID- 15440603
TI  - [Emergency neurosurgery; necessity for creating such services in Buenos Aires].

PMID- 15440605
TI  - [Hepatitis during the course of bartonellosis (Carrion's disease) study of 2
      cases with hepatobiliary function tests with special reference to the colloidal
      gold and cephalin-cholesterol reactions].

PMID- 15440606
TI  - [Large inguinal hernia with slipping of the iliopelvic colon; treatment].

PMID- 15440607
TI  - [Subacute symmetrical gangrene of the extremities].

PMID- 15440608
TI  - [Submucous lipoma of the cecum].

PMID- 15440609
TI  - [Hospital Beaujon of Paris].

PMID- 15440611
TI  - [Disorders of the gastrojejunal passage following stomach surgery; the so-called
      vicious circle].

PMID- 15440610
TI  - [Notes on a tour through the U.S.A..].

PMID- 15440612
TI  - [2 Cases of angiocellular reticuloblastomas; angioendothelioma of the bones].

PMID- 15440613
TI  - [Fibrositic nodular fever or the acute febrile nodular fibrositis syndrome].

PMID- 15440614
TI  - [Cancer of the colon].

PMID- 15440615
TI  - [Tolerance of chloromycetin].

PMID- 15440616
TI  - [Hypersensitivity of the skin to picric acid; simulation of accident].

PMID- 15440617
TI  - [Ant bites].

PMID- 15440618
TI  - [Dystocia due to multiple pregnancy].

PMID- 15440619
TI  - [Notes on a tour through the U.S.A..].

PMID- 15440621
TI  - [Causes of recurrent operations on the biliary tract].

PMID- 15440620
TI  - [Experimental study on the ethyl ester of bis-3-3'-(4-oxidocumarinyl)-acetic acid
      as an anticoagulant].

PMID- 15440622
TI  - [Action of subcutaneous injection of carbogen on arterial tension].

PMID- 15440623
TI  - [Aortoiliac thrombosis].

PMID- 15440624
TI  - [External hepatostomy].

PMID- 15440625
TI  - [Course of allergic disease at the Hospital Rivadavia; differential diagnosis of
      bronchial asthma from acute circulatory disorders].

PMID- 15440626
TI  - [Transverse infraumbilical laparotomy, Cherney's incision].

PMID- 15440627
TI  - [Elimination of 17-ketosteroids in rheumatoid arthritis].

PMID- 15440628
TI  - [History of breast surgery].

PMID- 15440629
TI  - [Effect of extracts of pregnant mare urine on gastroduodenal ulcers].

PMID- 15440630
TI  - [Notes on a tour through the U.S.A..].

PMID- 15440631
TI  - [Hormone therapy in gastroduodenal ulcer].

PMID- 15440632
TI  - [Treatment of scabies with hexachlorocyclohexane].

PMID- 15440633
TI  - [Skin reactions during PAS therapy].

PMID- 15440635
TI  - [Dystocia due to double monsters].

PMID- 15440634
TI  - [Work performed in the Section of Surgery of the liver, biliary tract, duodeno
      pancreas and spleen in 1949].

PMID- 15440636
TI  - [Elimination of 17-ketosteroids in gout].

PMID- 15440637
TI  - [Anesthesia in pediatrics; warming of ether vapor].

PMID- 15440638
TI  - [Progress of therapy in internal medicine in 1949; digestive system].

PMID- 15440639
TI  - [Notes on a tour of the USA].

PMID- 15440640
TI  - [Physicians and diseases of General San Martin during his campaigns].

PMID- 15440641
TI  - [Results of PAS therapy of tuberculous pleural empyema].

PMID- 15440642
TI  - [Vulvo-urethral carcinoma].

PMID- 15440643
TI  - [Surgical revascularization of the brain].

PMID- 15440644
TI  - [Leiomyosarcoma of rectovaginal septum].

PMID- 15440645
TI  - [Treatment of prolapse of the rectum by cerclage].

PMID- 15440646
TI  - [Early diagnosis and treatment of cancer].

PMID- 15440648
TI  - [Vagotomy: review of the present state of the problem].

PMID- 15440647
TI  - [Progress of therapy in internal medicine in 1949; digestive system].

PMID- 15440649
TI  - [Functional uterine hemorrhage].

PMID- 15440650
TI  - [Current problem of tuberculosis].

PMID- 15440651
TI  - [Chloroquine in the treatment of amebic abscess of the liver].

PMID- 15440652
TI  - [Dramamin in the treatment of hyperemesis of pregnancy].

PMID- 15440653
TI  - [Clinicopathological session; amebic abscess of liver, with complications].

PMID- 15440654
TI  - [Arterial grafts in the treatment of congenital malformations of the heart].

PMID- 15440655
TI  - [Two cases of single direction uterovesical fistula, following segmental
      abdominal cesarean section].

PMID- 15440656
TI  - [17-Ketosteroids and tuberculosis].

PMID- 15440657
TI  - [Recent concepts of diabetic coma; diagnosis and treatment].

PMID- 15440658
TI  - [A cause of error in pulmonary radiology: the tubercles of the first rib].

PMID- 15440659
TI  - [Under the white flag with blue cross: impressions and teachings of a medical
      mission to Finland].

PMID- 15440661
TI  - [Metamerization of the lesions of peptic ulcer; pathogenic deductions].

PMID- 15440660
TI  - [Psychosurgery; postoperative radiological control by lipiodol gelatin].

PMID- 15440662
TI  - [Action of 21-acetoxy-pregnenolone compared with that of desoxycorticosterone
      acetate and Kendall's compound E on experimental arthritis].

PMID- 15440663
TI  - [Cushing's disease and cancer of the pancreas].

PMID- 15440664
TI  - [The role of pyruvism in certain diseases of the lung].

PMID- 15440665
TI  - [Pulmonary tuberculosis treated with TBI].

PMID- 15440666
TI  - [Vater's ampulloma treated by papillectomy; recurrence; choledochoduodenostomy].

PMID- 15440667
TI  - [Fissures of 2 lumbar vertebral pedicles].

PMID- 15440668
TI  - [Anserine (Potentilla anserina L.) in the treatment of dysmenorrhea].

PMID- 15440669
TI  - [Anti-coagulant treatment of recent phlebitis of the lower extremity].

PMID- 15440670
TI  - [A case of death during treatment for alcoholism with tetradimethyluramide
      disulfite].

PMID- 15440671
TI  - [Rickets in Correze].

PMID- 15440672
TI  - [Controlateral atelectasis in the course of a therapeutic pneumothorax].

PMID- 15440673
TI  - [Nylon sutures].

PMID- 15440674
TI  - [Use of the descending colon and the left part of the transverse colon for
      prethoracic esophagoplasty].

PMID- 15440675
TI  - [Cybernetics; the comparative psychophysiology of thinking machines].

PMID- 15440676
TI  - [Determination of chlorides of the cerebro-spinal fluid in the diagnosis and
      conduct of treatment of tuberculous meningitis].

PMID- 15440677
TI  - [Some little known cardiac manifestations of staphylococcemia].

PMID- 15440678
TI  - [Vaginal smears].

PMID- 15440679
TI  - [Traumatic lesions in athletes].

PMID- 15440680
TI  - [Results of hormonal treatment of prostatic cancer].

PMID- 15440681
TI  - [Action of novocaine on traumatic and neurovegetative pain].

PMID- 15440682
TI  - [Manganese poisoning in Moroccan mines].

PMID- 15440684
TI  - [Surgical treatment of acquired heart disease].

PMID- 15440683
TI  - [Tumors of Vater's ampulla].

PMID- 15440685
TI  - [Prothrombin; its determination and significance].

PMID- 15440686
TI  - [Physiopathology of hemorrhages].

PMID- 15440687
TI  - [Medical secrecy].

PMID- 15440688
TI  - [Rapid evaluation of the streptomycin resistance of tubercle bacilli showing the
      percentage of sensitive and resistant organisms].

PMID- 15440689
TI  - [From the vascular phenomena of inflammation to the anti-inflammatory
      substances].

PMID- 15440690
TI  - [Anesthesia with rectanol in surgery of the nose and sinuses].

PMID- 15440691
TI  - [Metrorrhagia produced during the premenstrual phase by the injection of
      progesterone in women with normal menstrual cycles].

PMID- 15440692
TI  - [Intra-aortic transfusion].

PMID- 15440693
TI  - [Phenothiazinyl-ethyldiethylamine (2.987 R.P.) in anesthesia].

PMID- 15440695
TI  - [Treatment of Parkinson's syndrome by trihexylphenidyl (artane)].

PMID- 15440694
TI  - [Conessine in the treatment of vaginitis due to Trichomonas].

PMID- 15440697
TI  - [A new mercurial diuretic].

PMID- 15440696
TI  - [Physiology of the cold bath and its accidents].

PMID- 15440698
TI  - [Bornholm's disease and the Coxsackie virus].

PMID- 15440699
TI  - [Indications for thymectomy in myasthenia].

PMID- 15440700
TI  - [Conditions of hospitalization of women with torpid pulmonary tuberculosis].

PMID- 15440701
TI  - [The lack of hospital beds for patients with pulmonary tuberculosis suggests a
      new policy for sanatorium organization].

PMID- 15440703
TI  - [Trichloracetic acid in therapy].

PMID- 15440702
TI  - [The antibiotic of choice].

PMID- 15440704
TI  - [Amebiasis and emetine].

PMID- 15440705
TI  - [A journey to North Africa or a mission of the Alliance Francaise].

PMID- 15440706
TI  - [Cytological diagnosis of prostatic cancer].

PMID- 15440707
TI  - [Treatment of left ventricle insufficiency].

PMID- 15440708
TI  - [Scapulo-humeral periarthritis].

PMID- 15440709
TI  - [Sodium gentisate as a therapeutic agent in Bouillaud's disease].

PMID- 15440710
TI  - [Laboratory methods for estimating the value of a hemorrhage; a critical study].

PMID- 15440711
TI  - [Biological diagnosis of pregnancy; adaptation of the Galli-Mainini reaction to
      the common French toad].

PMID- 15440712
TI  - [Surgical closure of a preternatural anus].

PMID- 15440714
TI  - [Thermal and mechanical lesions caused by the atom bomb].

PMID- 15440713
TI  - [Not Available].

PMID- 15440715
TI  - [Radioactive effects of atomic explosion].

PMID- 15440716
TI  - [Delayed hematological effects of atom bombs].

PMID- 15440717
TI  - [Explosive and incendiary bombing of cities].

PMID- 15440718
TI  - [Scientific research on the medical protection of the population against war].

PMID- 15440719
TI  - [Treatment of shock in modern war].

PMID- 15440720
TI  - [The Rosenthal test in general irradiation due to ionizing radiations].

PMID- 15440721
TI  - [Medicine and physicians in China].

PMID- 15440722
TI  - [Infection in the newborn and aureomycin].

PMID- 15440723
TI  - [Research on the mechanism of cortical exclusion in burns].

PMID- 15440724
TI  - [Histaminolytic index of the mother's blood in retention of a dead fetus].

PMID- 15440725
TI  - [Use of sodium bicarbonate as an anticoagulant and the application of this method
      to blood transfusion].

PMID- 15440726
TI  - [Undecylenic acid and psoriasis].

PMID- 15440727
TI  - [Seventeenth century French vocabulary].

PMID- 15440728
TI  - [Apparatus for the determination of basal metabolism].

PMID- 15440730
TI  - [Economic rehabilitation of the handicapped].

PMID- 15440729
TI  - [Early recognition of invalidism].

PMID- 15440731
TI  - [Experience in the economic rehabilitation of the handicapped].

PMID- 15440732
TI  - [The handicapped and the vocational counsellor].

PMID- 15440733
TI  - [The handicapped and unemployment in Swiss legislation].

PMID- 15440734
TI  - [Problem in determining whether acid-fast bacilli found in gastric lavage are of
      pulmonary origin].

PMID- 15440735
TI  - [Origin of tubercle bacilli detected in gastric lavage].

PMID- 15440736
TI  - [Importance of examination of gastric and bronchial lavage for tubercle bacilli].

PMID- 15440737
TI  - [Presence of acidfast bacilli in the absence of marked tuberculous modifications
      in the lungs].

PMID- 15440738
TI  - [Effect of penicillin and other antibiotics on tubercle bacilli].

PMID- 15440739
TI  - [Artificial pneumothorax and atmospheric pressure].

PMID- 15440740
TI  - [Method of auscultation in diagnosis of tuberculosis in children].

PMID- 15440741
TI  - [Roentgen diagnosis of interlobular pleurisy].

PMID- 15440742
TI  - [Remote results of cautery of pleural adhesions in ineffective pneumothorax].

PMID- 15440743
TI  - [Artificial pneumothorax].

PMID- 15440744
TI  - [Tuberculosis of the trachea and main bronchi].

PMID- 15440745
TI  - [Certain errors in application of artificial pneumothorax].

PMID- 15440746
TI  - [Therapeutic pneumoperitoneum in tuberculosis].

PMID- 15440747
TI  - [Tissue therapy in pulmonary and laryngeal tuberculosis].

PMID- 15440748
TI  - [Bronchial obturation and condition of tuberculous cavern].

PMID- 15440749
TI  - [Effect of vitamin D2 on osteo-articular infections in skin tuberculosis].

PMID- 15440750
TI  - [Treatment of skin tuberculosis with calcium chloride, ascorbic acid and
      suberythematous dosages of quartz lamp].

PMID- 15440751
TI  - [Indications for surgical intervention on the pleural cavity in treatment of
      tuberculous].

PMID- 15440752
TI  - [Rare complications in pleural puncture].

PMID- 15440753
TI  - [Neuritis and neuralgia of brachial plexus of tuberculous origin].

PMID- 15440754
TI  - [Timely detection of tuberculosis according to data of tuberculosis].

PMID- 15440755
TI  - [Rehabilitation of tuberculous veterans of World War II].

PMID- 15440756
TI  - [Effect of diphtheria antitoxin in tuberculous infection].

PMID- 15440757
TI  - The effect of irregular absorption on galaxy distribution.

PMID- 15440758
TI  - The mechanism of action of a bacterial toxin on plant cells.

PMID- 15440759
TI  - Growth-promoting properties of quinic acid.

PMID- 15440760
TI  - Further studies on the purine and pyrimidine metabolism of Tetrahymena.

PMID- 15440761
TI  - Partial ordering in theory of stochastic processes.

PMID- 15440762
TI  - Cohomology theory of abelian groups and homotopy theory I.

PMID- 15440764
TI  - The surgery of otosclerosis.

PMID- 15440763
TI  - Remarks on the comparison of axiom systems.

PMID- 15440765
TI  - Oral pathology in children.

PMID- 15440766
TI  - Discussion on faints and fits.

PMID- 15440767
TI  - Biochemical methods in the treatment of alcoholism, with special reference to
      antabuse.

PMID- 15440768
TI  - Discussion on the mechanisms of disease production by ectoparasites.

PMID- 15440769
TI  - Isolation and chemistry of vitamin B12.

PMID- 15440770
TI  - Vitamin B12 and other dietary factors in megaloblastic anaemias and in subacute
      combined degeneration of the cord.

PMID- 15440771
TI  - Observations on the relationship between the red cell and reticulocyte responses
      and changes in the bone-marrow of patients suffering from pernicious anaemia
      treated with injections of liver extracts of vitamin B12.

PMID- 15440772
TI  - Endarteriectomy in the treatment of chronic endarteritis obliterans of the limbs
      and abdominal aorta.

PMID- 15440773
TI  - Psoriasis arthropathica.

PMID- 15440774
TI  - Pemphigus vegetans treated with aureomycin.

PMID- 15440775
TI  - Neurofibromatous naevus.

PMID- 15440776
TI  - Sisters with familial benign chronic pemphigus (Gougerot, Hailey and Hailey).

PMID- 15440777
TI  - Erythema multiforme perstans (erythema elevatum diutinum).

PMID- 15440779
TI  - Exfoliative erythrodermia with lymphadenopathy.

PMID- 15440778
TI  - Macular atrophy in syphilis.

PMID- 15440780
TI  - Infant feeding-bottles in prehistoric times.

PMID- 15440781
TI  - Ancient Egypt and the origin of anatomical science.

PMID- 15440782
TI  - Humphry Davy's contribution to anaesthesia.

PMID- 15440783
TI  - A colorimetric method for determination of sulfhydryl groups in tissue
      homogenates by 1-(4-chloromercuriphenylazo)-naphthol-2.

PMID- 15440784
TI  - Hemolysis of erythrocytes incubated in salines.

PMID- 15440785
TI  - Effects on anaphylactic shock of salicylates, aminopyrine and other chemically
      and pharmacologically related compounds.

PMID- 15440786
TI  - Effect of metal combining globulin (fraction IV-7) in severe Mediterranean
      anemia.

PMID- 15440787
TI  - Absorption and excretion of terramycin in humans: comparison with aureomycin and
      chloramphenicol.

PMID- 15440788
TI  - Dispersion oxygenation for effecting survival of dogs breathing pure nitrogen for
      prolonged periods.

PMID- 15440789
TI  - A method with perfused feline hearts of quantitatively comparing drugs with
      coronary vasodilating activity.

PMID- 15440790
TI  - Affinity of avidin for biocytin.

PMID- 15440791
TI  - Apparent free histidine plasma and urine values in rheumatoid arthritis treated
      with cortisone and ACTH.

PMID- 15440792
TI  - Mucolytic enzyme systems XIII; effect of compounds on hyaluronidase and its
      inhibition by human serum.

PMID- 15440793
TI  - 11-dehydrocorticosterone acetate (compound A) in normal and tumor bearing mice.

PMID- 15440794
TI  - Role of the pituitary in growth of a transplanted rat tumor.

PMID- 15440795
TI  - Blood flow determinations and cardiodynamic effects of a venous shunt in
      pulmonary hypertension.

PMID- 15440796
TI  - Maternal nutrition and hydrocephalus in newborn rats.

PMID- 15440797
TI  - The cockroach as an experimental vector of the virus of spontaneous mouse
      encephalomyelitis (Theiler).

PMID- 15440798
TI  - Influence of diphenhydramine on blood pressure response to epinephrine in the dog
      under adrenergic blockade.

PMID- 15440799
TI  - Response of circulating eosinophils to nor-epinephrine, epinephrine and emotional
      stress in humans.

PMID- 15440800
TI  - Radioautography of cerebral tumors employing P32.

PMID- 15440801
TI  - Estrogenic and gonadotrophic hormone inhibiting activity of some adrenal cortical
      substances.

PMID- 15440802
TI  - Effect of folic acid, aminopterin and vitamin K on growth of roots of Allium
      cepa.

PMID- 15440803
TI  - Biuret reaction as applied to determination of antibody nitrogen.

PMID- 15440804
TI  - Effect of intravenous injection of tuberculin on leucocytes of normal and
      tuberculous rabbits.

PMID- 15440805
TI  - Measurement of renal hemodynamics in man by the "slope method" without
      urinalysis.

PMID- 15440806
TI  - Pharmacology of isomeric thiocyanobenzoic acids.

PMID- 15440807
TI  - Increases in serum thyroxin during uncomplicated pregnancy.

PMID- 15440808
TI  - Differentiation between bacterial and tryptic gelatin liquefaction as aid to
      diagnosis of fibrosis of pancreas.

PMID- 15440809
TI  - Relative efficacy upon Pasteurella multocida of various antibiotics aureomycin,
      terramycin, bacitracin, and polymyxin B.

PMID- 15440810
TI  - Eosinophil response to epinephrine and nor-epinephrine.

PMID- 15440811
TI  - Sex difference in the response of rats to sodium pentobarbital.

PMID- 15440812
TI  - Biocytin in bacterial deamination of aspartic acid.

PMID- 15440813
TI  - Presence of secretin in cystic fibrosis of the pancreas.

PMID- 15440814
TI  - Effect of adrenalectomy on radiation induced mortality of the mouse.

PMID- 15440815
TI  - Effect of sodium salicylate on antibodies produced in guinea pigs.

PMID- 15440816
TI  - Use of antitryptic agents in tissue culture; II. egg-white antitrypsin.

PMID- 15440817
TI  - Antibacterial activity of hydrolyzed red blood cells in vitro.

PMID- 15440818
TI  - Antigenic identity of Shigella alkalescens type I and Kauffmann's Escherichia O
      group 1.

PMID- 15440819
TI  - Changes of the Ta wave in standard leads following stimulation of the vagus
      nerves.

PMID- 15440820
TI  - Anticomplementary properties of bone marrow in certain diseases.

PMID- 15440821
TI  - Milk agent and natural antisheep agglutinins in mice of inbred strains.

PMID- 15440822
TI  - Interrelationships of desoxycorticosterone, cortisone and vitamin C in the
      genesis of mesenchymal lesions.

PMID- 15440823
TI  - Effect of tolerance on inhibition of respiration of brain homogenates by
      thiopental.

PMID- 15440824
TI  - A method for quantitative estimation of small amounts of D-tubocurarine chloride
      in plasma.

PMID- 15440825
TI  - Experimental production of sterile closed intestinal loops.

PMID- 15440826
TI  - Utilization of the labile factor during normal and abnormal coagulation of blood.

PMID- 15440827
TI  - The use of cortisone and ACTH in rheumatoid disease in swine.

PMID- 15440828
TI  - Mechanism of increased susceptibility to ergot gangrene in thyrotoxicosis.

PMID- 15440829
TI  - Effect of hyperglycemicglycogenolytic factor on blood sugar or patients with
      diabetes.

PMID- 15440830
TI  - Ultraviolet photography of paper chromatograms in the study of nucleic acids.

PMID- 15440831
TI  - Amino acids of nervous tissue.

PMID- 15440832
TI  - Protective effect of fibrinogen on accelerator globulin.

PMID- 15440833
TI  - Distribution of an unidentified antithyrotoxic factor in materials of plant and
      animal origin.

PMID- 15440834
TI  - Absorption, distribution and excretion of phenindamine (thephorin).

PMID- 15440835
TI  - Relationships of vital capacity and ventilatory measurements to physical fitness
      in patients with cardio-respiratory diseases.

PMID- 15440836
TI  - Cardiovascular changes induced by rapid expansion of the extracellular fluid.

PMID- 15440837
TI  - On the mechanism of action of aminopterin.

PMID- 15440838
TI  - Tocopherol requirements of rats by means of the hemolysis test.

PMID- 15440839
TI  - Experimental control of serum calcium levels in vivo.

PMID- 15440840
TI  - Effect of physical factors on radiosodium clearance from subcutaneous and
      intramuscular sites in animals.

PMID- 15440841
TI  - Activity of ethyl-1-ethanesulfonyl-4-piperazine hydrochloride on traumatic
      hemorrhagic shock on the dog.

PMID- 15440842
TI  - Prothrombin utilization during clotting: comparison of results with the two-stage
      and one-stage methods.

PMID- 15440843
TI  - A diabetes insipidus-like condition produced in dogs by a potassium deficient
      diet.

PMID- 15440844
TI  - Lymphocytic response of normal individuals to transient hyper- and hypoglycemia.

PMID- 15440845
TI  - A small bore polythene shunt to prevent mechanical shock after prolonged cross
      clamping thoracic aorta.

PMID- 15440846
TI  - Use of a glass edge in thin sectioning for electron microscopy.

PMID- 15440847
TI  - Absorption and distribution of vitamin A in x-irradiated rats.

PMID- 15440848
TI  - Presence of desoxyribonuclease activity in human serum.

PMID- 15440849
TI  - A colorimetric procedure for the determination of aspartic acid.

PMID- 15440850
TI  - Methylene blue, 2,4-dinitrophenol, and oxygen uptake of intact and homogenized
      embryos.

PMID- 15440851
TI  - Metabolism of C13-carboxyl-labeled malonate by the intact mouse.

PMID- 15440852
TI  - Antibiotics in the treatment of experimental acute hemorrhagic pancreatitis in
      dogs.

PMID- 15440853
TI  - Pituitary basophile hyperplasia and Crooke's hyaline changes in man after ACTH
      therapy.

PMID- 15440854
TI  - Experimental nephrotoxic nephritis in the rat treated with ACTH or cortisone.

PMID- 15440855
TI  - Distribution of radioiodine in erythrocytes and plasma of man.

PMID- 15440856
TI  - Toxic effect on the chick embryo of homologous tissue suspensions following
      intravenous inoculation.

PMID- 15440857
TI  - The preparation and biological activity of alpha estradiol-sensitized collodion
      particles.

PMID- 15440858
TI  - Preparation of a water emulsion of alpha-tocopherylhydroquinone suitable for
      intravenous administration in animals.

PMID- 15440859
TI  - Unusual antigenic variation in an enteric bacterium.

PMID- 15440860
TI  - Potassium uptake of normal and low potassium human red corpuscles.

PMID- 15440861
TI  - In vitro sensitivity of bacteria to sulfonamide combinations as compared to
      single sulfonamides.

PMID- 15440862
TI  - Effect of exercise upon liver following partial hepatectomy in albino rats.

PMID- 15440863
TI  - Chymotrypsin inhibition by human serum in health and disease.

PMID- 15440864
TI  - Effect of hypothalamic lesions on the peripheral blood picture of the cat.

PMID- 15440865
TI  - Effects of irradiation on nucleic acid formation.

PMID- 15440866
TI  - Further experiments on influence of hyaluronidase on formation of intraperitoneal
      adhesions in the rat.

PMID- 15440867
TI  - Polysaccharides in ulcerative colitis and normal human rectum compared by stains
      of biopsy specimens.

PMID- 15440868
TI  - Metabolism and excretion of estrone sulfate labeled with radioactive sulfur
      (S35).

PMID- 15440869
TI  - Antibiotic studies on beta hemolytic streptococci: VII. Acquired in vitro
      resistance to bacitracin.

PMID- 15440870
TI  - The cultivation of Coxsackie virus.

PMID- 15440871
TI  - Chronic toxicity of thiomerin compared to other mercurial diuretics.

PMID- 15440872
TI  - Pancreatic secretion to peptic ulcer. II. Effect of hypoglycemia with and without
      pancreatectomy.

PMID- 15440873
TI  - Virus interference by serially passed Hodgkin's disease extracts in chicken eggs.

PMID- 15440874
TI  - Neutralization of pit viper venom by king snake serum.

PMID- 15440875
TI  - Loss of insulin hypersensitivity and development of diabetes in hypophysectomized
      dogs produced by purified growth hormone.

PMID- 15440876
TI  - Effects of b-diethylaminoethyl xanthene 9-carboxylate methobromide (banthine) on
      human gastrointestinal function.

PMID- 15440877
TI  - Effect of cortisone and adrenocorticotropin therapy on serum proteins in
      disseminated lupus erythematous.

PMID- 15440878
TI  - Achromotrichia due to copper deficiency.

PMID- 15440879
TI  - Formation of neutralizing antibody in monkeys injected with poliomyelitis virus
      and adjuvants.

PMID- 15440880
TI  - Lack of effect of lactogenic hormone on mammary adenocarcinoma in mice.

PMID- 15440881
TI  - Incomplete growth cycle of influenza virus in mouse brain.

PMID- 15440882
TI  - Absence of digitalis-like cardiac effects in the action pattern of several simple
      lactones.

PMID- 15440883
TI  - A new technic for the continuous recording of the cardiac output.

PMID- 15440884
TI  - Susceptibilities of pleuropneumonia-like organisms to some selective
      bacteriostatic agents.

PMID- 15440885
TI  - Production, purification, and some properties of Clostridium histolyticum
      collagenase.

PMID- 15440886
TI  - Pteroylglutamic acid-like effect of dehydroisoandrosterone on growth of certain
      microorganisms.

PMID- 15440887
TI  - On hemolysis mediated by non-erythrocytic antigens, their homologous antibodies
      and complement.

PMID- 15440888
TI  - A direct relationship between indoleacetic acid effects on growth and reducing
      sugar in tobacco tissue.

PMID- 15440889
TI  - Effect of carbohydrate on growth response to vitamin B12 in the hyperthyroid rat.

PMID- 15440890
TI  - Role of protogen in the nutrition of an unidentified Corynebacterium.

PMID- 15440891
TI  - Applicability of a differential analyzer to determination of protein fractions by
      the electrophoretic technic.

PMID- 15440892
TI  - Simultaneous bilateral determinations of cerebral blood flow and arterial
      cerebral venous oxygen and glucose differences.

PMID- 15440893
TI  - Diurnal variations of renal function in congestive heart failure.

PMID- 15440894
TI  - Effect of certain amines on the blood pressure of normotensive and hypertensive
      rats.

PMID- 15440895
TI  - The use of radon seeds to produce deep cerebral lesions.

PMID- 15440896
TI  - Effects of prolonged exposure to cold on the vitamin A requirement of the rat.

PMID- 15440897
TI  - Oxybiotin in the bacterial deamination of aspartic acid.

PMID- 15440898
TI  - Effect of hepatectomy upon the analgetic action of 1 methadone.

PMID- 15440899
TI  - Persistence of Brunhilde poliomyelitis virus in rodent brain without evidence of
      adaptation.

PMID- 15440900
TI  - p-Anisaldehyde-thiosemicarbazone in treatment of experimental murine
      tuberculosis.

PMID- 15440901
TI  - A comparative study of susceptibility of tubercle bacillus (H37RV) to aureomycin,
      streptomycin, and para-aminosalicylic acid.

PMID- 15440902
TI  - Effect of aminoguanidine on formaldehyde poisoning in rats.

PMID- 15440903
TI  - Development of resistance to folic acid antagonists in a transplantable lymphoid
      leukemia.

PMID- 15440904
TI  - Diabetic state with lipaemia and hydropic changes in the pancreas produced in
      rabbits by cortisone.

PMID- 15440905
TI  - Alterations in rate of influenza virus proliferation produced by growth hormone
      and testosterone.

PMID- 15440906
TI  - A rapid method for detection of influenza virus during epidemics.

PMID- 15440907
TI  - Influence of sex hormones on tolerance to aminopterin.

PMID- 15440908
TI  - Inositol and the toxicity of four isomers of benzenehexachloride for the rat.

PMID- 15440909
TI  - Some effects of testosterone propionate on mice irradiated with x-rays.

PMID- 15440910
TI  - Formation of the beta-carbon of serine from formaldehyde.

PMID- 15440911
TI  - Preparation of water-soluble combination products of gossypol and their toxicity
      to aquarium fish.

PMID- 15440912
TI  - Lipotropic effects of liver extract, vitamin B12 and choline.

PMID- 15440913
TI  - Effect of B complex vitamins on liver and heart glycogen levels of hyperthyroid
      rats.

PMID- 15440914
TI  - Progestational activity of 1.2-bis-(p-aminophenyl)-2-methylpropanone-1
      dihydrochloride.

PMID- 15440915
TI  - Effects of radioactive iodine on free sarcoma 37 cells in the peritoneal fluid of
      the mouse.

PMID- 15440916
TI  - Distribution and effect of colloidal radioactive gold in peritoneal fluid
      containing free sarcoma 37 cells.

PMID- 15440917
TI  - A simple chromatographic procedure for the separation of angiotonin from crude
      mixtures.

PMID- 15440918
TI  - Direct determinations of plasma, cell, and organ-blood volumes in normal and
      hypervolemic mice.

PMID- 15440919
TI  - Potentiation of androgen by aqueous aluminum phosphate suspension.

PMID- 15440920
TI  - Inhibition of the phagocytic action of leucocytes by mumps and influenza viruses.

PMID- 15440921
TI  - A note on electrophoresis in hypothyroidism.

PMID- 15440922
TI  - Introduction: cortisone and ACTH in clinical medicine.

PMID- 15440923
TI  - Effects of cortisone and ACTH on patients with rheumatoid arthritis.

PMID- 15440924
TI  - Effects of cortisone and ACTH in 14 patients with acute rheumatic fever.

PMID- 15440925
TI  - Effects of cortisone on acute disseminated lupus erythematosus.

PMID- 15440926
TI  - Effects of cortisone on bronchial asthma and hay fever occurring in subjects
      sensitive to ragweed pollen.

PMID- 15440927
TI  - Experiences with cortisone and ACTH in chronic ulcerative colitis.

PMID- 15440928
TI  - Cortisone and ACTH in the management of leukemia and lymphoblastoma.

PMID- 15440929
TI  - Effects of cortisone on certain opthalmic diseases.

PMID- 15440930
TI  - The action of cortisone in nephritis with edema.

PMID- 15440931
TI  - Effects of cortisone and ACTH on periarteritis nodosa and cranial arteritis.

PMID- 15440932
TI  - Use of cortisone and ACTH in certain diseases: psychiatric aspects.

PMID- 15440933
TI  - Effects of cortisone and ACTH in certain endocrine conditions.

PMID- 15440934
TI  - Cortisone in neurologic diseases.

PMID- 15440936
TI  - Carcinoma of the upper thoracic and cervical portions of the esophagus treated by
      one-stage esophagectomy and cervical esophagogastrostomy: report of 2 cases.

PMID- 15440935
TI  - Summary: cortisone and ACTH in clinical medicine.

PMID- 15440937
TI  - The origin and evolution of diagnostic procedures with reference to diseases of
      the heart and circulation. VI. Roentgenography of the heart and great vessels.

PMID- 15440938
TI  - Arrested hydrocephalus: report of case.

PMID- 15440939
TI  - Adenocarcinoma of the fundus after epithelioma of the cervix: report of case.

PMID- 15440940
TI  - Histories and physical findings in 50 cases of chondromalacia of the patella.

PMID- 15440941
TI  - [Pharmacy of 12 plants; tobacco insecticide].

PMID- 15440942
TI  - [French industrial research in pharmaceutical chemistry].

PMID- 15440943
TI  - [Chloromycetin and aureomycin].

PMID- 15440944
TI  - [Pharmacodynamic comparison between an alcoholic tincture of Anemone pulsatilla
      L. Codex and a tincture prepared from the powder of anemone pulsatilla].

PMID- 15440945
TI  - [Research on the determination of urinary albumin in the presence of P.V.P.
      (polyvinylpyrolidone)].

PMID- 15440946
TI  - [New method of administration of medicaments: implantation of tablets of
      crystallized compounds].

PMID- 15440947
TI  - [Chemistry and biology of carnosine; a chemical study].

PMID- 15440948
TI  - [Chemical industry in Great Britain].

PMID- 15440949
TI  - [Antituberculous medicaments].

PMID- 15440950
TI  - [The philosophy of surgery].

PMID- 15440951
TI  - [Diabetes and pregnancy].

PMID- 15440952
TI  - [Study of the biologic diagnosis of pregnancy by means of the male Rana
      esculenta].

PMID- 15440953
TI  - [The medical world during the siege of Mayence].

PMID- 15440954
TI  - [Philosophy of surgery].

PMID- 15440955
TI  - [A hundred years of French surgery].

PMID- 15440956
TI  - [French medical Europe in the "Siecle des lumieres"].

PMID- 15440957
TI  - [Ambroise Pare as seen by Merimee and Balzac].

PMID- 15440958
TI  - [Study on the distribution and causes of accidents provoked by anti-veneral
      arsenicals reported in certain countries].

PMID- 15440959
TI  - [Results obtained by the use of single or multiple injections of procaine
      penicillin in oil and aluminum monostearate in the treatment of early syphilis].

PMID- 15440960
TI  - [The problem of syphilitic heredity].

PMID- 15440961
TI  - [Notes on the social consequences of hereditary syphilis].

PMID- 15440962
TI  - [Problem of congenital syphilis in France].

PMID- 15440963
TI  - [Study of the problem of prostitution and of the related social measures].

PMID- 15440964
TI  - [Problem of prostitution and the principles of its solution in Poland].

PMID- 15440965
TI  - [On the solution of the sanitary problem of prostitution, in France].

PMID- 15440966
TI  - [Venereal diseases and prostitution in Morocco].

PMID- 15440968
TI  - [Not Available].

PMID- 15440967
TI  - [Health chart; continued surveillance of the development of the child].

PMID- 15440969
TI  - [The Terman-Merrill test].

PMID- 15440970
TI  - [The psychology of irony; analysis of the novel by Anatole France, Le Jongleur de
      Notre Dame].

PMID- 15440971
TI  - [Chopin and the maternal breast].

PMID- 15440972
TI  - [Not Available].

PMID- 15440973
TI  - [The totalitarianism of the schools of psychoanalysis].

PMID- 15440974
TI  - [The Virgin in French art].

PMID- 15440975
TI  - [Role of the autonomic nervous system in pupillotonia and Adie's syndrome].

PMID- 15440976
TI  - [Blood protein values in epilepsy and their relation to seizure].

PMID- 15440977
TI  - [Remedial education of criminal psychopaths; observations and experiences from
      the years 1929-1933].

PMID- 15440978
TI  - [Traumatic cerebral dysfunction syndrome in the Rorschach test].

PMID- 15440979
TI  - [Sociology and psychology of the dionysian].

PMID- 15440980
TI  - Paul Federn, 1872-1950.

PMID- 15440981
TI  - The prepuberty trauma in girls.

PMID- 15440982
TI  - Mucous colitis associated with phobias.

PMID- 15440983
TI  - Obsessive-compulsive symptoms in an incipient schizophrenic.

PMID- 15440985
TI  - Psychoanalysis and the social structure.

PMID- 15440984
TI  - The interpretation of the trauma as a command.

PMID- 15440986
TI  - The application of psychoanalytic concepts to social science.

PMID- 15440987
TI  - Unsatisfactory results of psychoanalytic therapy.

PMID- 15440988
TI  - The oedipal legend in Christian hagiology.

PMID- 15440989
TI  - Repression as a factor in learning theory.

PMID- 15440990
TI  - The distinction between loving and being loved.

PMID- 15440991
TI  - Some psychological problems of economics.

PMID- 15440992
TI  - The misuse of chi-square a reply to Lewis and Burke.

PMID- 15440993
TI  - Some comments on "The use and misuse of the chi-square test".

PMID- 15440994
TI  - On "The use and misuse of the chi-square test"--the case of the 2x2 contingency
      table.

PMID- 15440995
TI  - Further discussion of the use and misuse of the chi-square test.

PMID- 15440996
TI  - Are theories of learning necessary?

PMID- 15440997
TI  - An operational approach to some problems in psychological measurement.

PMID- 15440998
TI  - A note on McGinnies' "Emotionality and perceptual defense".

PMID- 15440999
TI  - Discussion of Howes' and Solomon's note on "Emotionality and perceptual defense".

PMID- 15441000
TI  - Multiple operation measurement.

PMID- 15441001
TI  - The problem of classification of personnel.

PMID- 15441002
TI  - Changes in common-factor loadings as tests are altered homogeneously in length.

PMID- 15441003
TI  - A test of the equality of standard errors of measurement.

PMID- 15441004
TI  - The reliability of speeded tests.

PMID- 15441006
TI  - An experimental study of the effects on item-analysis data of changing item
      placement and test time limit.

PMID- 15441005
TI  - The discrimination of two racial samples.

PMID- 15441007
TI  - A proposed method for absolute ratio scaling.

PMID- 15441008
TI  - Salmonellosis in man and animals.

PMID- 15441009
TI  - Some medical aspects of atomic warfare.

PMID- 15441010
TI  - OUR medical officers of health; a study of the metropolitan medical officers of
      health, 1855-60.

PMID- 15441011
TI  - Some observations on the problem of the cerebral palsied child.

PMID- 15441013
TI  - HENRY Hyslop Thompson.

PMID- 15441012
TI  - EDWARD William Hope.

PMID- 15441014
TI  - New paths in public health.

PMID- 15441015
TI  - What is child guidance?

PMID- 15441016
TI  - The Department of Human Ecology and the medical officer of health.

PMID- 15441017
TI  - Some recent developments in health statistics--international, national and local.

PMID- 15441018
TI  - Poliomyelitis in a rural Scottish county, 1947, 1948 and 1949.

PMID- 15441019
TI  - Citizen participation in public health nursing; opportunities for citizen
      participation.

PMID- 15441020
TI  - Citizen participation in public health nursing; a program for volunteers.

PMID- 15441021
TI  - Citizen participation in public health nursing; day to day activities of board
      members.

PMID- 15441022
TI  - Citizen participation in public health nursing; Citizen's Advisory Committee in
      an official agency.

PMID- 15441023
TI  - A practical approach to a salary study.

PMID- 15441024
TI  - TEAMWORK in the home care of the cancer patient.

PMID- 15441025
TI  - NURSE mental health consultant; functions and qualifications.

PMID- 15441026
TI  - Public health nursing studies and inservice education.

PMID- 15441027
TI  - Bellevue Hospital's home care transfer program.

PMID- 15441028
TI  - Effect of formaldehyde on the direct microscopic count of raw milk.

PMID- 15441029
TI  - Field tests of molluscacides against Australorbis glabratus in endemic areas of
      schistosomiasis in Puerto Rico.

PMID- 15441030
TI  - The visual identification of V and W form colonies in Salmonella cultures.

PMID- 15441031
TI  - INCIDENCE of disease.

PMID- 15441032
TI  - Licensure of BCG vaccine.

PMID- 15441033
TI  - Further observations on histoplasmosis; mycology and bacteriology.

PMID- 15441034
TI  - INCIDENCE of disease.

PMID- 15441035
TI  - The physiological response to dust from mine locomotive traction material.

PMID- 15441036
TI  - 1080 (Sodium fluoroacetate) poisoning of rats on ships.

PMID- 15441037
TI  - INCIDENCE of disease.

PMID- 15441038
TI  - Bactericidal efficiency of quaternary ammonium compounds.

PMID- 15441039
TI  - Haplomycosis in Montana rabbits, rodents, and carnivores.

PMID- 15441040
TI  - COMMUNITIES awarded milk sanitation ratings of 90 percent or more, July 1948-June
      1950.

PMID- 15441041
TI  - INCIDENCE of disease.

PMID- 15441042
TI  - Two surveys of methods used by public health laboratories for the examination of
      stool specimens for Salmonellae, Shigellae, and protozoa.

PMID- 15441043
TI  - The role of morbidity reporting and case registers in cancer control.

PMID- 15441044
TI  - PUBLIC health service publications July-December 1949.

PMID- 15441045
TI  - INCIDENCE of disease.

PMID- 15441046
TI  - Studies of pulmonary findings and antigen sensitivity among student nurses;
      geographic differences in sensitivity to tuberculin as evidence of nonspecific
      allergy.

PMID- 15441047
TI  - Geographic distribution of pulmonary calcification among university students in
      Ohio.

PMID- 15441048
TI  - INCIDENCE of disease.

PMID- 15441049
TI  - Relapse following apparent arrest of leprosy by sulfone therapy.

PMID- 15441050
TI  - REPORTED incidence of communicable diseases in the United States, second quarter,
      1950.

PMID- 15441051
TI  - INCIDENCE of disease.

PMID- 15441052
TI  - [Hormone therapy as complementary treatment of cancer of the uterus].

PMID- 15441054
TI  - [Lacerations of the cervix and cancer].

PMID- 15441053
TI  - [Therapy of pyelocystitis of pregnancy with p-aminosalicylic acid].

PMID- 15441055
TI  - [Stilbene implant therapy in ovarian rheumatism].

PMID- 15441056
TI  - [Fetal peritonitis from meconium].

PMID- 15441057
TI  - [Pregnancy and the synthetizing power of the liver (resorcin test)].

PMID- 15441058
TI  - [Neurovegetative lability and postoperative tachycardia].

PMID- 15441059
TI  - [Use of testosterone with slow absorption in the therapy of some gynecological
      disorders].

PMID- 15441060
TI  - [Variations in the metabolism of patients with cancer of the uterus subjected to
      radiotherapy].

PMID- 15441061
TI  - [Clinico-statistical considerations on transverse position of the fetus].

PMID- 15441062
TI  - The effect of alcohol on liver lipids and on liver and heart glycogen.

PMID- 15441063
TI  - Chloride levels in the blood of alcoholic patients in relation to the phenomenon
      of craving.

PMID- 15441064
TI  - Acetaldehyde in relation to intoxication by ethyl alcohol.

PMID- 15441065
TI  - The role of acetaldehyde in the toxicity of tetraethylthiuram disulfide and
      alcohol; with a method for the determination of acetaldehyde in 0.20 Ml. of
      blood.

PMID- 15441066
TI  - Alcoholism and the acute abdomen.

PMID- 15441067
TI  - A transference phenomenon in alcoholics; its therapeutic implications.

PMID- 15441068
TI  - The Washingtonian movement.

PMID- 15441070
TI  - Alcoholism in Ayurveda.

PMID- 15441069
TI  - Drinking patterns of Italians in New Haven; utilization of the personal diary as
      a research technique. III. Diaries 6 and 7.

PMID- 15441071
TI  - After retirement, what?

PMID- 15441072
TI  - Patients have families too.

PMID- 15441073
TI  - The value of experience.

PMID- 15441074
TI  - SOLAR sense.

PMID- 15441075
TI  - ATOMIC repercussions.

PMID- 15441076
TI  - The eighth art.

PMID- 15441077
TI  - Radiography of the biliary tract.

PMID- 15441078
TI  - A technique on facial maxillary injuries.

PMID- 15441079
TI  - Automatic replenishment of the developing solution in x-ray work.

PMID- 15441080
TI  - [Early roentgen diagnosis of gastric cancer].

PMID- 15441081
TI  - [Two cases of schwannoma of the stomach].

PMID- 15441082
TI  - [Clinical experience with nitrogen mustard].

PMID- 15441083
TI  - [Effect of roentgen rays on a few simple aliphatic bromine compounds].

PMID- 15441084
TI  - [Case of duodenal tumor].

PMID- 15441085
TI  - [Segments and segmentary diseases of the lung].

PMID- 15441086
TI  - [Diaphragmatic hernia of Morgagni].

PMID- 15441088
TI  - [Diagnostic possibilities of catheterization of the heart by the venous route].

PMID- 15441087
TI  - [Pulmonary syphilis; appearance and regression of gumma in the course of specific
      treatment].

PMID- 15441089
TI  - [Alternately retrograde and anterograde colo-colic invagination in tumor of the
      colon].

PMID- 15441090
TI  - [High right aorta; three-dimensional stratigraphy].

PMID- 15441091
TI  - [A case of generalized osteosclerosis].

PMID- 15441092
TI  - [Pyloritis].

PMID- 15441093
TI  - [The radiological picture in articular alterations of late congenital syphilis].

PMID- 15441094
TI  - [Clinico-statistical report of carcinomas of the mouth and pharynx treated from
      1928-1945. III. Results of radiotherapy in carcinomas of the glosso-palatine
      region and of the anterior palatine pilaster (110 cases)].

PMID- 15441095
TI  - [The M. Gortan Institute of Radiology and Radium therapy of the Ospedale Maggiore
      of Trieste].

PMID- 15441096
TI  - Non-significant ventricular shift in pneumoencephalograms with particular
      reference to bowing of the septum pellucidum.

PMID- 15441097
TI  - Primary tumors of the small intestine.

PMID- 15441098
TI  - General considerations in the roentgen examination of the colon.

PMID- 15441099
TI  - High renal ectopia and congenital diaphragmatic hernia.

PMID- 15441100
TI  - High-voltage technic in the diagnosis of polypoid growths of the colon.

PMID- 15441101
TI  - Acromioclavicular changes in primary and secondary hyperparathyroidism.

PMID- 15441102
TI  - Roentgen diagnosis of subdiaphragmatic abscess.

PMID- 15441103
TI  - Treatment of antral cancer by combined surgery and radium therapy.

PMID- 15441104
TI  - Treatment of carcinoma of the nasopharynx by irradiation.

PMID- 15441105
TI  - Supervoltage roentgen therapy in cancer of the mouth and throat.

PMID- 15441106
TI  - Surgical management of cervical lymph node metastases.

PMID- 15441107
TI  - Treatment of cervical lymph node metastases with irradiation alone.

PMID- 15441108
TI  - Roentgen demonstration of the common duct entering a duodenal diverticulum.

PMID- 15441109
TI  - Electrokymographic observations in constrictive pericarditis.

PMID- 15441110
TI  - Retroperitoneal emphysema from perforation of an intraperitoneal viscus.

PMID- 15441111
TI  - Clinical studies of the use of emulsion of ethyl iodophenylundecylate
      (pantopaque).

PMID- 15441112
TI  - New bone formation associated with direct extension from lymph node metastases to
      bone in infiltrating carcinoma of the bladder.

PMID- 15441113
TI  - New trends in radiographic screening technics utilizing Schmidt optical systems
      and high-speed development.

PMID- 15441114
TI  - A new type of x-ray cassette cabinet.

PMID- 15441115
TI  - Acquired radioresistance of the crypt epithelium of the duodenum.

PMID- 15441116
TI  - Concerning the radiologist and the future.

PMID- 15441117
TI  - IN MEMORIAM Frank S. Windholz, M. D.

PMID- 15441118
TI  - The role of the internist in the detection and early diagnosis of gastric
      carcinoma.

PMID- 15441120
TI  - Examination of the stomach by "oil contrast".

PMID- 15441119
TI  - Standard radiologic methods used in the search for gastric tumors.

PMID- 15441121
TI  - The histologic characteristics and growth behavior of primary gastric tumors.

PMID- 15441122
TI  - Present status of the surgical treatment of gastric tumors.

PMID- 15441123
TI  - Upper gastrointestinal examination after gastric surgery.

PMID- 15441124
TI  - Plasma-cell tumor of the stomach; with report of a case.

PMID- 15441125
TI  - Cardio-esophageal relaxation; report of three cases.

PMID- 15441126
TI  - Perforation of peptic ulcer; a roentgenologic consideration of the various forms
      and uncommon types of perforation.

PMID- 15441127
TI  - Radiation therapy of carcinoma of the cardia.

PMID- 15441128
TI  - Segmental collapse in therapeutic pneumothorax.

PMID- 15441129
TI  - Sacroiliac joint changes in traumatic paraplegics.

PMID- 15441130
TI  - Hemorrhage from a Meckel's diverticulum as a cause of melena in infancy; report
      of a case in which the diverticulum was demonstrated roentgenographically.

PMID- 15441131
TI  - Spontaneous pneumaturia with report of a case.

PMID- 15441132
TI  - Aneurysm of the pulmonary artery; a case diagnosed by angiocardiography.

PMID- 15441133
TI  - Carcinoma associated with diaphragmatic herniation of the stomach.

PMID- 15441134
TI  - Million-volt beryllium-window x-ray equipment for biophysical and biochemical
      research.

PMID- 15441135
TI  - Axial transverse laminagraphy.

PMID- 15441136
TI  - The linea innominata.

PMID- 15441137
TI  - James Currie McMillan, M. D., 1883-1950.

PMID- 15441138
TI  - [Pathogenesis of megaloblastic anemia].

PMID- 15441139
TI  - [Present status of the problem of shock; shock as a biological phenomenon].

PMID- 15441140
TI  - [Adsorbed anatoxins].

PMID- 15441142
TI  - [Local treatment of tinea without depilation].

PMID- 15441141
TI  - [Atomic disease].

PMID- 15441144
TI  - [Considerations on three cases of Fox-Fordyce disease].

PMID- 15441143
TI  - [Influence of 2-3 dimercaptopropanol on arsenobenzolic coproporphyrinuria].

PMID- 15441145
TI  - [Curative action of streptomycin in experimental syphilis in the rabbit].

PMID- 15441147
TI  - [Edema due to circulatory decompensation].

PMID- 15441146
TI  - [A case of neuroectomesodermal dysplasia (Pringle's adenoma sebaceum associated
      with retinal phacomatosis, periungual fibromatosis and unusual bone
      modifications].

PMID- 15441148
TI  - [Chronic anemia of blood-letting after ligature of the portal vein].

PMID- 15441149
TI  - [Experimental atherosclerosis; lipid blood fractions of the rabbit on
      hypercholesterol diet and treatment with lipotropes].

PMID- 15441150
TI  - [Behavior of blood concentration and elimination in the urine of p-aminosalicylic
      acid after administration of substances with retarding action; experimental and
      clinical research].

PMID- 15441151
TI  - [Experimental research on the histidine and arginine content of the blood serum
      following surgery with various anesthetics].

PMID- 15441152
TI  - [Dynamics of the heart in normal subjects; graphic and chronometric study of the
      systole time].

PMID- 15441153
TI  - [Androstenediol dipropionate and cirrhosis of the liver].

PMID- 15441154
TI  - [Treatment of pulmonary suppurations with endobronchial antibiotics].

PMID- 15441155
TI  - [Use of p-aminosalicylic acid in the treatment of tuberculosis; clinical
      contribution].

PMID- 15441156
TI  - [Blood concentration and elimination of p-aminosalicylic acid].

PMID- 15441157
TI  - [Muscular lesions in athletes].

PMID- 15441158
TI  - [Penicillin therapy in metasyphilitic diseases].

PMID- 15441159
TI  - [Aspecific reaction to cadmium and blood sedimentation rate in pulmonary
      tuberculosis].

PMID- 15441160
TI  - [Experimental research on the problem of the hemorrhagic syndrome caused by
      administration of nitrogen mustards].

PMID- 15441161
TI  - [Cutaneo-hematic reaction in dystonia of the vegetative nervous system].

PMID- 15441162
TI  - [Acute leukemic myelosis].

PMID- 15441163
TI  - [Successive relations between pernicious anemia and carcinoma of the stomach].

PMID- 15441164
TI  - [Case of hemocytoblastic leukemia].

PMID- 15441165
TI  - [Hypochromic anemia in subjects with diaphragmatic hernia; case].

PMID- 15441166
TI  - [Two cases of acute leukopenic leukemia].

PMID- 15441167
TI  - [Case of congestive splenomegaly].

PMID- 15441168
TI  - [Phases of aplasia occurring in the course of polycythemia].

PMID- 15441169
TI  - [Di Guglielmo's erythroleukemic myelosis].

PMID- 15441170
TI  - [Interesting case of primary tumor of the lymph glands].

PMID- 15441171
TI  - [Clinical importance of sideremia].

PMID- 15441172
TI  - [Vitamin-hormone therapy in rheumatic diseases].

PMID- 15441173
TI  - [Brucellosis simulating endocarditis lenta cured by aureomycin].

PMID- 15441174
TI  - [Specific defense proteases as a practical index for tuberculosis diagnosis].

PMID- 15441175
TI  - [Sclerogummous syphilis of the submaxillary gland].

PMID- 15441176
TI  - [Variations in cupremia following intravenous injections of copper gluconate in
      hepatic diseases].

PMID- 15441177
TI  - [Clinical contribution to acute abdomen caused by rupture of luteo-follicular
      hematic cysts].

PMID- 15441178
TI  - [Diagnosis and treatment of acute coronary diseases].

PMID- 15441179
TI  - [Medicinal specialties; proposal for publicity less expensive and more adapted to
      the psychology of the physician].

PMID- 15441180
TI  - [Vasomotor action of recorcaine and sindrenin administered intravenously, in
      successive doses, in arterial hypertension].

PMID- 15441181
TI  - [Tryptophan test in spinal fluid in tuberculous meningitis].

PMID- 15441182
TI  - [Paralytic syndromes of association in malignant tumors of the nasopharynx;
      review note].

PMID- 15441183
TI  - [Glycogenosis].

PMID- 15441184
TI  - [A specific test for recognizing a dental focal infection].

PMID- 15441185
TI  - [Chloromycetin therapy in peritonitis caused by appendicitis].

PMID- 15441186
TI  - [Sintomicetina and intravenous vaccine in salmonellosis; clinical note].

PMID- 15441187
TI  - [Chloramphenicol therapy in whooping cough].

PMID- 15441188
TI  - [Treatment with chloramphenicol in Haemophilus pertussis infection].

PMID- 15441189
TI  - [Several cases of typhoid treated with chloramphenicol].

PMID- 15441190
TI  - [First results of the study of the anti-treponemic action of chloramphenicol].

PMID- 15441191
TI  - [Action of chloramphenicol in venereology].

PMID- 15441192
TI  - [Clinical observations on 5 cases of brucellosis treated with the sodium salt of
      p-aminosalicylic acid].

PMID- 15441193
TI  - [Multiphasic procedure in the diagnostic examination of demographic
      collectivities].

PMID- 15441194
TI  - [Caronamide and streptomycin; experimental tests on the blood level of
      streptomycin with administration of 4-benzylsulfonamidebenzoic acid and sodium
      benzoate].

PMID- 15441195
TI  - [A case of nymphomania treated with pineal gland extract].

PMID- 15441196
TI  - [Hemorrhagic complications of treatment with dicumarol].

PMID- 15441197
TI  - [p-Aminobenzoic acid in the prevention of sunburn].

PMID- 15441198
TI  - [An original method of craniometric localization].

PMID- 15441199
TI  - [Action of p-aminobenzoic and p-aminosalicylic acids on the blood crasis of
      children].

PMID- 15441200
TI  - [Hypertension following toxemia of pregnancy].

PMID- 15441201
TI  - [Possibilities and limitations in surgery of pulmonary tuberculosis].

PMID- 15441202
TI  - [Possibilities and orientations of modern cardiovascular surgery].

PMID- 15441203
TI  - [Favism; first observations on the familial blood picture and serological
      alterations in patients with favism].

PMID- 15441204
TI  - [A year of industrial control and prevention of tetraethyl lead poisoning].

PMID- 15441205
TI  - [Importance of medical prophylaxis for the health and productivity of workers].

PMID- 15441206
TI  - [Endarterial penicillin-novocain therapy in acute inflammation of the
      extremities].

PMID- 15441207
TI  - [Rotary press in the typographic industry; hints on occupational diseases and
      industrial prophylaxis].

PMID- 15441208
TI  - [Manual composition in the typographic industry; notes on occupational diseases
      and industrial prophylaxis].

PMID- 15441209
TI  - [Functional changes in vegetative rhythm].

PMID- 15441210
TI  - [Experimental research on renal circulation; ischemic adrenalin kidney; action of
      dihydroergotamine on the adrenalin kidney].

PMID- 15441211
TI  - [Experimental research on renal circulation; neurogenic renal ischemia; action of
      anesthesia and of dihydroergotamine on the ischemic kidney].

PMID- 15441212
TI  - [Histaminic reactivity and provoked headache in relation to hematic histaminase
      and to endocrine variations in pregnancy and puerperium].

PMID- 15441213
TI  - [Allergometry and velocity of sedimentation in dyshormoneurovegetative states and
      in neurovegetative syndromes associated with chronic sinu-perisinusitis].

PMID- 15441214
TI  - [Radiological panorama of headaches].

PMID- 15441215
TI  - [Small signs in roentgencraniography].

PMID- 15441216
TI  - [Albright syndrome].

PMID- 15441217
TI  - [Antihistamine action of dihydroergotamine].

PMID- 15441218
TI  - [From the personal unconscious of Freud to the collective unconscious of Jung].

PMID- 15441219
TI  - [Individual peculiarities of the recovery phase following electroshock].

PMID- 15441220
TI  - [Diagnostic value and clinico-nosological significance of syndromes of the
      obsessive-phobic type in the ambit of schizophrenia].

PMID- 15441221
TI  - [Head injuries in neuropsychiatry; permanent paralysis of the abducens and
      facial, paresis of the cochlear branch of the VIII by apical fracture of the
      petrous bone].

PMID- 15441222
TI  - [Difficulty of diagnosis in neoplasms of the vertebral cavity].

PMID- 15441223
TI  - [Behavior of the Alexeiev-Schramm phenomenon in some nervous system diseases].

PMID- 15441224
TI  - [Intracranial tumors in children; clinicoanatomopathological contribution].

PMID- 15441225
TI  - [Anomalous segmental forms of syringomyelia; clinico-statistical contribution].

PMID- 15441226
TI  - [Statistical study of crimes in terms of criminality].

PMID- 15441227
TI  - [Treatment of toxicomania; modern methods of disintoxication and deprivation in
      chronic addiction of euphoric type].

PMID- 15441228
TI  - [Peculiar behavior of intradermoreaction to choline and acetylcholine in
      schizophrenia].

PMID- 15441229
TI  - [Psychopathic personality and habitual criminality].

PMID- 15441230
TI  - [Amoral personality and habitual criminality].

PMID- 15441231
TI  - [Electroencephalographic contribution to the study of the impulsive personality].

PMID- 15441232
TI  - [Notes on clinical psychometry; index of unbalance; coefficient of deterioration
      and the psi system].

PMID- 15441233
TI  - [Dysthymia and diffuse late syphilis of the brain].

PMID- 15441234
TI  - [Narcolepsy with oneirism and barbituric subnarcosis].

PMID- 15441235
TI  - [Nosographic findings on progressive paralysis].

PMID- 15441236
TI  - [Case of postpuerperal cerebral thrombophlebitis].

PMID- 15441237
TI  - [General physical condition of patients treated with intravenous acetylcholine in
      massive doses by the Fiamberti method].

PMID- 15441238
TI  - [A case of grave hemorrhage of the dental pulp].

PMID- 15441239
TI  - [Gingival cauterization and eosinophilic granuloma; experimental research].

PMID- 15441240
TI  - [Fluorine as a prophylactic measure in caries, taken internally or applied
      locally with a liquid or paste vehicle].

PMID- 15441242
TI  - Commentary: an evaluation of animal and human mentality.

PMID- 15441241
TI  - [New antibiotic treatment of infectious complications of dental origin by means
      of direct local transcutaneous injections].

PMID- 15441243
TI  - Measuring fringe orders in photoelasticity.

PMID- 15441244
TI  - Recent progress in refractories.

PMID- 15441245
TI  - Colorado beetle problem.

PMID- 15441246
TI  - Micromethods in histochemistry and cytochemistry.

PMID- 15441248
TI  - Forum: mathematics in the larger context.

PMID- 15441247
TI  - Forest Research Institute.

PMID- 15441249
TI  - Formation of Munroe jets and their action on massive targets.

PMID- 15441250
TI  - Estimation of the surface areas of powders from the temperature dependence of
      adsorption from solution.

PMID- 15441251
TI  - Iodine monochloride as an ionizing solvent.

PMID- 15441252
TI  - Synthesis of organo-silicon carboxylic acids.

PMID- 15441254
TI  - Japanese science and technology.

PMID- 15441253
TI  - Photoelectric methods for metal optics.

PMID- 15441255
TI  - Measurements in the upper air by radio sonde.

PMID- 15441256
TI  - Psychophysical relationships and their study.

PMID- 15441257
TI  - Chemoreceptors and regulation of respiration.

PMID- 15441258
TI  - Electrical properties of muscle fibre.

PMID- 15441259
TI  - Irrigation requirements in Spain.

PMID- 15441260
TI  - [Clinical and etiopathogenetic classification of coronary syndromes].

PMID- 15441261
TI  - [Roentgenotherapy in extrapulmonary tuberculosis].

PMID- 15441262
TI  - [A catatonic syndrome during treatment with urethane].

PMID- 15441263
TI  - The present status of the treatment of cirrhosis of the liver.

PMID- 15441264
TI  - Thoughts upon diabetes today.

PMID- 15441265
TI  - The antibiotics in gastrointestinal diseases.

PMID- 15441266
TI  - Recurrent inguinal hernia.

PMID- 15441268
TI  - Acute perforated peptic ulcer.

PMID- 15441269
TI  - Surgical aspects of diverticulitis of the sigmoid.

PMID- 15441270
TI  - Diaphragmatic hernia with report of a case.

PMID- 15441271
TI  - Treatment of giardiasis by the chloroguanide chlorhydrate.

PMID- 15441272
TI  - Corticodiencephalic gastrointestinal syndromes in epileptics. Part VII.

PMID- 15441273
TI  - Liver trauma.

PMID- 15441275
TI  - Complications and sequelae of gallbladder disease.

PMID- 15441274
TI  - Gastroenterological conditions and complications in the course of diabetes
      mellitus.

PMID- 15441276
TI  - Anesthesia for gastrointestinal surgery.

PMID- 15441277
TI  - Complications of acute appendicitis.

PMID- 15441278
TI  - Fasting achlorhydria and hypochlorhydria produced by protein hydrolysate therapy
      of peptic ulcer; a preliminary report.

PMID- 15441279
TI  - Colitis gravis.

PMID- 15441280
TI  - Corticodiencephalic gastrointestinal syndromes in epileptics.

PMID- 15441281
TI  - [Pulmonary cysts with mycotic content].

PMID- 15441282
TI  - [Determination of the cause, origin and responsibility in post-transfusional
      accidents].

PMID- 15441283
TI  - [Cyst of the ovary and renal colic].

PMID- 15441284
TI  - [Treatment of alcoholism with antabuse (tetraethylthiurane disulphide);
      importance of acetaldehyde].

PMID- 15441285
TI  - [Recklinghausen's disease; parathyroidectomy; remote results].

PMID- 15441286
TI  - [Partial avulsion of the genitals; its surgical, endocrine and psychological
      treatment].

PMID- 15441287
TI  - [Comments on the second meeting of the Committee of Experts of the World Health
      Organization, in Geneva].

PMID- 15441288
TI  - [Choleperitoneum: experimental contribution to its physiopathology].

PMID- 15441289
TI  - [Results of the treatment of pulmonary tuberculosis with streptomycin].

PMID- 15441290
TI  - [Roentgenotherapy in sarcoma of Waldeyer's ring].

PMID- 15441291
TI  - [p-Aminosalicylic acid in nontuberculous bronchial diseases].

PMID- 15441292
TI  - [Mechanism of fracture of the carpal scaphoid].

PMID- 15441293
TI  - [Giant cell granuloma of the adipose ligament of the knee].

PMID- 15441294
TI  - [Brunschwig operation].

PMID- 15441295
TI  - [Sudeck-Leriche disease].

PMID- 15441296
TI  - [Dislocation of the hip with fracture of the posterior wall of the acetabulum].

PMID- 15441297
TI  - [Nontropical sprue].

PMID- 15441298
TI  - [Definition of allergy].

PMID- 15441299
TI  - [Correction of prominent ears].

PMID- 15441300
TI  - [Surgical treatment of pulmonary tuberculosis by partial upper thoracoplasty;
      based on 577 operations].

PMID- 15441301
TI  - [Renal neoplasms in the adult].

PMID- 15441302
TI  - [Perineo-pelvic pan-viscerectomy for advanced cancer of the cervix].

PMID- 15441303
TI  - [Diverticula of the bladder; regarding a communication].

PMID- 15441304
TI  - [Cystoscopic appearance of non-specific cystitis].

PMID- 15441306
TI  - [Risks of sclerosing treatment of hydrocele].

PMID- 15441305
TI  - [Surgical treatment of pulmonary tuberculosis by partial upper thoracoplasty;
      based on 577 operations].

PMID- 15441307
TI  - [Osteomyelitis of the temporal bone].

PMID- 15441308
TI  - [Immunobiological relation between tuberculosis and leprosy; positive action of
      BCG on the lepromin test].

PMID- 15441309
TI  - [Importance and results of sulfone therapy in dispensaries].

PMID- 15441310
TI  - [Clinical aspects of leprosy: liver, kidneys, intestines].

PMID- 15441311
TI  - [Sulfone therapy in leprosy].

PMID- 15441312
TI  - [New rule for calculating the emptying of the gallbladder].

PMID- 15441313
TI  - [Gastroenterological manifestation of so-called scleroderma].

PMID- 15441314
TI  - [Auto genous vaccine in cases resistant to penicillin].

PMID- 15441315
TI  - [Treatment of cryptorchidism].

PMID- 15441316
TI  - [Treatment of schistosomiasis].

PMID- 15441317
TI  - [Allergic diseases of occupational origin].

PMID- 15441318
TI  - [Nutrition in northeast Brazil].

PMID- 15441319
TI  - [Influence of the medical working hours and remuneration on social justice].

PMID- 15441320
TI  - [Psychologism?].

PMID- 15441321
TI  - [Etiology and treatment of blushing].

PMID- 15441322
TI  - [Anesthesia in labor].

PMID- 15441323
TI  - [Medical and surgical indications in the treatment of gastric and duodenal
      ulcer].

PMID- 15441324
TI  - [Resistance of the chorionic hormone].

PMID- 15441325
TI  - [Serodiagnosis of syphilis by the Migliano reaction].

PMID- 15441326
TI  - [Painful abdominal point useful in the diagnosis and management of duodenal
      inflammation].

PMID- 15441327
TI  - [Substitution of fingers].

PMID- 15441328
TI  - [Use of vitamin C in asthma].

PMID- 15441329
TI  - [Pantropic viruses; pappataci fever virus].

PMID- 15441330
TI  - [Pantropic viruses; tick fever virus].

PMID- 15441331
TI  - [Giant cells in malignant epithelial tumors].

PMID- 15441332
TI  - [Epicrisis in a fatal case of ulcerative colitis].

PMID- 15441333
TI  - [The superiority of the northeastern Brazilian].

PMID- 15441334
TI  - [Differential diagnosis between benign hypertrophy and cancer of the prostate].

PMID- 15441335
TI  - [Progress in therapeutics and its dangers].

PMID- 15441336
TI  - [Fatal spontaneous hemopneumothorax].

PMID- 15441337
TI  - [Treatment of dentin; hyperesthesia of the dentin].

PMID- 15441338
TI  - [New absorbable substances and their use in oral surgery].

PMID- 15441339
TI  - [Periodontal pockets; etiopathogenesis, histopathology and treatment].

PMID- 15441340
TI  - [Psychological aspect of modern pedodontia].

PMID- 15441341
TI  - [Function of the frenum labiorum].

PMID- 15441342
TI  - [Blalock-Taussig operation in a case of tetralogy of Fallot].

PMID- 15441343
TI  - [Conjunctivitis of the newborn].

PMID- 15441344
TI  - [Erythrocyte and leukocyte count and determination of hematocrit, hemoglobin and
      mean corpuscle volume in 893 infants and children; statistical significance of
      the differences between the averages].

PMID- 15441346
TI  - [BCG vaccination and its clinical aspects].

PMID- 15441345
TI  - [Preventive vaccinations in children; antiwhooping cough-diptheria vaccine;
      antidiphtheria vaccine].

PMID- 15441347
TI  - [Capillary hemangioma of the uterus].

PMID- 15441348
TI  - [Meigs' syndrome; a typical case with special reference to the physiopathology of
      ascitic-pleural effusion].

PMID- 15441350
TI  - [Urethritis in women].

PMID- 15441349
TI  - [Examination of the permeability of the Fallopian tubes with the
      phenolsulfonphthalein test].

PMID- 15441351
TI  - [Streptococcus sanguis White in subacute bacterial endocarditis].

PMID- 15441352
TI  - [Appendicitis and tuberculosis].

PMID- 15441353
TI  - [Case of encephalitis cured with chloramphenicol].

PMID- 15441354
TI  - [Syphilis].

PMID- 15441355
TI  - [Therapeutic pneumothorax in tuberculosis in children].

PMID- 15441356
TI  - [Leprosy in children].

PMID- 15441357
TI  - [Septicopyemia].

PMID- 15441358
TI  - [Bone alterations in the cranial vault in congenital hemolytic jaundice].

PMID- 15441359
TI  - [Streptomycin in 2 cases of tuberculous meningitis tuberculosa].

PMID- 15441360
TI  - [Bronchial obstruction in the course of whooping cough in infants].

PMID- 15441361
TI  - [Deficiency disease of children].

PMID- 15441362
TI  - A case of paroxysmal supraventricular tachycardia or flutter in a newborn.

PMID- 15441363
TI  - [A study on the paracolon bacillus; use of diagnostic serum in children].

PMID- 15441364
TI  - [Preliminary report on the satisfactory treatment of amebiasis with a new
      antibiotic, bacitracin].

PMID- 15441365
TI  - [Etiology and treatment of infectious diarrhea in children].

PMID- 15441366
TI  - [New hormone therapy with ACTH and cortisone].

PMID- 15441367
TI  - [Infections in humans caused by Salmonella cubana].

PMID- 15441368
TI  - [Disorders observed in diabetic children treated with free diet].

PMID- 15441369
TI  - [Hypertrophy of the thymus and tuberculosis of the tracheo-bronchial lymph
      glands; differential diagnosis by anterior artificial pneumomediastinum].

PMID- 15441370
TI  - [Rapid cure of osseous xanthomatosis with a single massive dose of vitamin A].

PMID- 15441371
TI  - [Dental caries from the pediatric viewpoint; current concepts].

PMID- 15441372
TI  - [Second European Congress of National Associations of Gastroenterology].

PMID- 15441373
TI  - [Study of duodenal bile in non-calculous infections of the gallbladder and bile
      ducts].

PMID- 15441374
TI  - [Pharmacology of the bile ducts].

PMID- 15441375
TI  - [Biochemical alterations of the plasma in biliary diseases].

PMID- 15441376
TI  - [Biliary dyskinesia; clinical, physiopathological and radiomanometric study].

PMID- 15441377
TI  - [Clinical diagnosis of functional disorders of the gallbladder and bile ducts].

PMID- 15441378
TI  - [Surgical treatment of biliary dyskinesia].

PMID- 15441379
TI  - [Etiology of cholecystitis].

PMID- 15441380
TI  - [Clinical aspect of non-calculous cholecystitis].

PMID- 15441381
TI  - [Radiology in non-calculous cholecystitis and cholangitis].

PMID- 15441382
TI  - [Non-calculous cholecystitis and cholangitis; pathological anatomy].

PMID- 15441383
TI  - [Medical treatment of non-calculous chronic cholecystitis].

PMID- 15441384
TI  - [Medical treatment of chronic cholecystitis].

PMID- 15441385
TI  - [Importance of inflammatory participation of the bile ducts in catarrhal
      jaundice].

PMID- 15441386
TI  - [Congenital anomalies of the bile ducts].

PMID- 15441387
TI  - [Acquired benign stenosis of the bile ducts, lithiasis excepted].

PMID- 15441388
TI  - [Duodenal intubation in non-calculous cholecystopathies].

PMID- 15441389
TI  - [Operative cholangiography].

PMID- 15441390
TI  - [Post-operative complications of gallbladder surgery and their treatment].

PMID- 15441392
TI  - [Bases and indications of functional surgery in biliary dyskinesia].

PMID- 15441391
TI  - [A new clinical form of cirrhosis of the liver; the hepato-enteropathy of
      megaloblastic anemia].

PMID- 15441393
TI  - [Duodenal intubation in the diagnosis of jaundice].

PMID- 15441394
TI  - [Ketonemia in cirrhosis of the liver].

PMID- 15441395
TI  - [New facts on the metabolism of water and the formation of edemas and ascitis in
      cirrhosis of the liver].

PMID- 15441396
TI  - [Taste hormones in the saliva].

PMID- 15441397
TI  - [Small intestine and vitamins].

PMID- 15441399
TI  - [Curability of meningitis due to Hemophilus influenzae].

PMID- 15441398
TI  - [First cases of infantile kala-azar treated in Spain with diamidines
      (stilbamidine and pentamidine)].

PMID- 15441400
TI  - [Infantile paralysis].

PMID- 15441401
TI  - [Barbituric intoxication in children].

PMID- 15441402
TI  - [Rh factor in Spain].

PMID- 15441403
TI  - [Malnutrition and hypovitaminosis after weaning].

PMID- 15441404
TI  - [Use of carob seed thickening powder].

PMID- 15441405
TI  - [Neuromyelitis optica].

PMID- 15441406
TI  - [Treatment of congenital equinovarus].

PMID- 15441407
TI  - [Treatment and prevention of epidemic parotitis with p-aminobenzoic acid].

PMID- 15441408
TI  - [Extrapleural pneumothorax. II. Management of complications].

PMID- 15441409
TI  - [Postthoracoplastic thoracovertebral deformity in infantile pulmonary
      tuberculosis].

PMID- 15441410
TI  - [Wilson block].

PMID- 15441411
TI  - [Regional pathology of the lung].

PMID- 15441412
TI  - [Tuberculin, histoplasmin, coccidioidin].

PMID- 15441413
TI  - [Tuberculous pericarditis and polyserositis; effective treatment with
      streptomycin].

PMID- 15441414
TI  - [Chlorine and potassium ions in pulmonary tuberculosis and action of the
      suprarenal cortex].

PMID- 15441415
TI  - [Study of the bacteriostatic and bactericidal power of antibrucellin: sulfonic
      derivative of 2 methyl-6 oxy-1,4 naphthoquinone: sal soda].

PMID- 15441416
TI  - [Antibrucellin in the treatment of human brucellosis].

PMID- 15441417
TI  - [Three cases of spinal cord compression].

PMID- 15441418
TI  - [Functional examination of the kidney in children with diffuse glomerulonephritis
      by means of simultaneous sulfophenolphthalein and urea clearance tests].

PMID- 15441419
TI  - [Experimental contributions to the pathogenic study of functional infarct of the
      small intestine].

PMID- 15441420
TI  - [Efficacy of streptomycin in granuloma venereum; two observations].

PMID- 15441421
TI  - [Contribution to the study and experimentation of dental reimplantations and
      grafts].

PMID- 15441422
TI  - [Marwen encephalomyelitis; a new virus pathogenic to man].

PMID- 15441423
TI  - [Vaginal smears and hormonal elimination during the menstrual cycle].

PMID- 15441424
TI  - [Hysterectomies in benign conditions].

PMID- 15441425
TI  - [Fibromyomas of the cervix uteri].

PMID- 15441426
TI  - [Red leiomyoma of the uterus].

PMID- 15441427
TI  - [Non-fatal birth injuries; paralysis and fractures; personal cases].

PMID- 15441428
TI  - [Granuloma venereum of the cervix].

PMID- 15441429
TI  - [Late ligation of the umbilical cord].

PMID- 15441430
TI  - [Vesicovaginal fistula operated on after childbirth].

PMID- 15441431
TI  - [Hepatic amebic abscess with pulmonary complication cured with tanakan
      (chloroquine)].

PMID- 15441432
TI  - [Filariasis of the epididymis; report of a first observation in Cuba].

PMID- 15441433
TI  - [Seven cases of hepatitis treated with chloroquine (tanakan)].

PMID- 15441434
TI  - [Perforated hepatic amebic abscess cured with emetine-chloroquine].

PMID- 15441435
TI  - [Contribution to the treatment of tuberculosis with p-aminosalicylic acid].

PMID- 15441436
TI  - [BAL in the treatment of intoxication by arsenical and gold preparations].

PMID- 15441437
TI  - [Caribe (cercaria dermatitis); extermination of cercaria].

PMID- 15441438
TI  - [Radionecrosis of the extremities and its treatment].

PMID- 15441439
TI  - [Captive lung].

PMID- 15441440
TI  - [The whisper in examination of hearing].

PMID- 15441441
TI  - [Bilateral cystadenoma of the ovary associated with ascites and hydrothorax
      (Meigs' syndrome)].

PMID- 15441442
TI  - [Subcostosternal diaphragmatic hernia].

PMID- 15441443
TI  - [Essential hypertension].

PMID- 15441444
TI  - [Psychology and psychotherapy].

PMID- 15441445
TI  - [Persistent vitreous hemorrhage in hemophilia].

PMID- 15441447
TI  - [Leukocyte oxidase and hemoglobin].

PMID- 15441446
TI  - [Specific therapy of pneumonia].

PMID- 15441448
TI  - [Quinones as protective substances against dental caries].

PMID- 15441449
TI  - [Kidney function tests].

PMID- 15441450
TI  - [Sodium thiosulfate clearance in normal subjects].

PMID- 15441451
TI  - [Physiopathological aspects of pancreas changes in chronic cholecystopathy].

PMID- 15441452
TI  - [Electrophoretic study of plasma and serum proteins in rheumatoid arthritis; its
      comparison with flocculation and other tests].

PMID- 15441453
TI  - [Experimental studies on the peripheral action of hydergin].

PMID- 15441454
TI  - [Histaminic action of the perienteric fluid of the Ascaris lumbricoides var.
      suum].

PMID- 15441455
TI  - [Obstruction of the jejunum by a chyliferous cyst of the mesentery].

PMID- 15441456
TI  - [Subarachnoid hemorrhage].

PMID- 15441457
TI  - [Typhoid fever in hospitals].

PMID- 15441458
TI  - [Multiple plasma cell myeloma of myelogenous plasmocytoma (Kahler's disease)
      blood protein picture and urinary modifications].

PMID- 15441459
TI  - [Electrophoretic study of blood proteins in infectious hepatitis].

PMID- 15441460
TI  - [Varicocele; delayed results of the combined operation; ligation and resection of
      the spermatic veins by the Ivanissevich method, associated with fixation of the
      testis].

PMID- 15441461
TI  - [Measurement of blood coagulation].

PMID- 15441462
TI  - [A pyloric syndrome due to hematic cyst of the pancreas].

PMID- 15441463
TI  - [PROFESSOR Ernesto Prado Tagle].

PMID- 15441464
TI  - [Prolongation of penicillinemia by implants of tablets of procaine penicillin].

PMID- 15441465
TI  - [Renal function and renal hemodynamics in essential hypertension].

PMID- 15441466
TI  - [Early menopause and hormone therapy].

PMID- 15441467
TI  - [Determination of total neutral 17-ketosteroids in the urine; standard method and
      its clinical value].

PMID- 15441468
TI  - [Human distomiasis].

PMID- 15441469
TI  - [Psychogenic headaches].

PMID- 15441470
TI  - [Etiopathogenesis of rheumatic fever].

PMID- 15441471
TI  - [Hypersensitivity to streptomycin].

PMID- 15441472
TI  - [Diphyllobothrium latum in Chile; the first humar autochthonous case].

PMID- 15441473
TI  - [Quantitative evolution of complement subfractions in the course of certain acute
      infectious diseases].

PMID- 15441474
TI  - [Desoxycorticosterone acetate and ascorbic acid in the treatment of rheumatoid
      arthritis].

PMID- 15441475
TI  - [Flocculation test with double distilled water].

PMID- 15441476
TI  - [Modern drugs in the treatment of parkinsonism and similar diseases].

PMID- 15441477
TI  - [Aerosols of streptomycin in the treatment of bronchial asthma].

PMID- 15441478
TI  - [Uses and abuses of the male hormone (testosterone) treatment in women; its use
      in cancer].

PMID- 15441479
TI  - [Case of Addison's disease treated with methyltestosterone pellets].

PMID- 15441480
TI  - [Case of intestinal myiasis caused by Psychoda Sp..].

PMID- 15441481
TI  - [Biochemistry of histamine].

PMID- 15441482
TI  - [Clinical and physiological aspects of blood coagulation].

PMID- 15441483
TI  - [Action of sulfonamides on the growth of gram negative intestinal bacteria].

PMID- 15441484
TI  - [Problem of premature labor].

PMID- 15441485
TI  - [Cardiorespiratory function in thoracoplasty or extrapleural pneumothorax in
      pulmonary tuberculosis].

PMID- 15441486
TI  - [Perception of heart tones at a distance due to cavernous resonance and broncho
      tracheo-laryngo-buccal air transmission].

PMID- 15441487
TI  - [Extraperitoneal ureterosigmoidostomy].

PMID- 15441488
TI  - [Chronic pancreatitis; diagnosis and treatment].

PMID- 15441489
TI  - [Theory of pharmacodynamic action in relation to the principle of the phenomenon
      of competition].

PMID- 15441490
TI  - [Post-operative shock and internal hemorrhage].

PMID- 15441491
TI  - [Pathology and therapy of lesions caused by the atomic bomb].

PMID- 15441492
TI  - [Low spinal anesthesia in surgery and obstetrics].

PMID- 15441493
TI  - [Alcoholism].

PMID- 15441494
TI  - [Human case of intestinal coccidiosis caused by Isospora hominis; first published
      case in Peru].

PMID- 15441495
TI  - [Retrovesical hydatid cyst opening into the bladder].

PMID- 15441496
TI  - [The Hospital Arzobispo Loayza on its silver anniversary].

PMID- 15441497
TI  - [Sodium salicylate in the treatment of rheumatic fever].

PMID- 15441498
TI  - [Rupture of the bladder following pelvic injuries].

PMID- 15441499
TI  - [202 cases of typhoid fever; comparative study of the antibiotic activity of
      racemic and levogyric chloramphenicol in 139 patients].

PMID- 15441500
TI  - [Forceps at the Instituto Simon Rodraguez].

PMID- 15441501
TI  - [Abdominal pregnancy at term with live fetus].

PMID- 15441502
TI  - [Manual extraction of the placenta].

PMID- 15441503
TI  - [Compensation of the hospitalized cardiac patient by the Gold method; preliminary
      results in a Sao Paulo hospital].

PMID- 15441504
TI  - [Treatment of posttransfusion anuria by renal decapsulation].

PMID- 15441505
TI  - [Congenital atresia of the esophagus; 3 cases].

PMID- 15441506
TI  - [Suppurated mesenteric lymphadenitis].

PMID- 15441507
TI  - [Formation of a renal calculus after a lumbar injury].

PMID- 15441508
TI  - [Delayed retroperitoneal urinary extravasation following lumbar ureterolithotomy,
      with exteriorization of an abdominal tumor].

PMID- 15441509
TI  - [A new apparatus for measuring skin temperature of the extremities].

PMID- 15441510
TI  - [Divulsion forceps].

PMID- 15441511
TI  - [Indices of the natural infection of snails by the cercaria of Schistosoma
      mansoni in Salvador].

PMID- 15441512
TI  - [Schistosomiasis in Ceara].

PMID- 15441513
TI  - [Boeck's sarcoid; a neurosurgical case].

PMID- 15441514
TI  - [Spinal fluid in Weil's disease].

PMID- 15441516
TI  - [Treatment of purulent meningitis].

PMID- 15441515
TI  - [Clinical interpretation of the quantitative Wassermann reaction].

PMID- 15441517
TI  - [Clinical considerations on Chagas' disease].

PMID- 15441518
TI  - [Diphtheria meningitis].

PMID- 15441519
TI  - [Tuberculosis of adenoma of the prostate].

PMID- 15441520
TI  - [Planigraphy and its importance in the diagnosis of diseases of the thorax].

PMID- 15441521
TI  - [The clinical picture of thromboangiitis obliterans; 35 cases].

PMID- 15441522
TI  - [Diverticula of the duodenum; 6 cases].

PMID- 15441523
TI  - [Results of use of diparcol in the treatment of parkinsonian syndromes].

PMID- 15441524
TI  - [Results of research on intestinal parasitoses in 100 pathergic patients].

PMID- 15441525
TI  - [New instrument for temporary vascular hemostasis].

PMID- 15441526
TI  - [Epidemiology of the rickettsial diseases in the state of Sao Paulo].

PMID- 15441527
TI  - [Present state of anesthesia in England and certain experiments carried out in
      the laboratories of the Imperial Chemical Manufacturing Co..].

PMID- 15441528
TI  - [Kyphoscoliotic paraplegia; neurosurgical therapy; transposition of the spinal
      cord; therapeutic success].

PMID- 15441529
TI  - [Immunobiological relation between tuberculosis and leprosy; positivating action
      of BCG on the Mitsuda reaction].

PMID- 15441530
TI  - [Symposium on penicillin therapy in gynecology].

PMID- 15441531
TI  - [Pelvic presentation in primiparas over 30].

PMID- 15441532
TI  - [Radiological signs of premature detachment of the normally inserted placenta].

PMID- 15441533
TI  - [Coccidioidomycosis: a new problem of public health in Venezuela].

PMID- 15441534
TI  - [A semi-automatic filing system for pharmaceutical products classified by
      pharmacologic groups].

PMID- 15441535
TI  - [Malignant tumors of the nasopharyngeal region; lymphosarcoma of the nasopharynx;
      solitary plasmocytoma of the anterior wall of the nasopharynx].

PMID- 15441536
TI  - [Malaria in Venezuela; introduction to the study of Anophele darlingi].

PMID- 15441537
TI  - [Study of endemia of alastrim in the area of Caracas, 1945-1949].

PMID- 15441538
TI  - [Treatment of syphilis in pregnancy with penicillin].

PMID- 15441539
TI  - [Anopheles of Spain and the Spanish zone of the Protectorate of Morocco; their
      relation to the spread of malaria].

PMID- 15441540
TI  - [Public health situation in India].

PMID- 15441541
TI  - [Morbidity of reportable diseases in 1950; comparative study].

PMID- 15441543
TI  - [Present state of the campaign against measles].

PMID- 15441542
TI  - [Human encephalitis produced by virus].

PMID- 15441544
TI  - [Unification of human and veterinary antirabies vaccination].

PMID- 15441545
TI  - [A new antibiotic: terramycin].

PMID- 15441546
TI  - [Morbidity of reportable diseases in 1950; comparative study].

PMID- 15441547
TI  - [Effect of ion concentration of potassium, calcium and magnesium of the
      cerebrospinal fluid on respiration].

PMID- 15441548
TI  - [Effect of ion concentration of calcium, potassium and magnesium in the cerebral
      ventricles on oxygen consumption].

PMID- 15441549
TI  - [Influences of vagus and spinal (or accessory) nerves and of superior cervical
      ganglion on the gastric motility].

PMID- 15441550
TI  - [Contribution to the study of osseous dysplasia: anatomico-clinical description
      of a case of polymorphous osteosarcoma in a child with osseous fibroxanthoma and
      sexual prematurity].

PMID- 15441551
TI  - [Inlay and onlay abutments for molars and premolars].

PMID- 15441552
TI  - [Injuries of the permanent incisors in the young].

PMID- 15441553
TI  - [Foreign bodies in the air passage and the esophagus].

PMID- 15441554
TI  - [Use of the electron microscope].

PMID- 15441555
TI  - [On Dr. Le Huche's article concerning inlay and onlay abutments].

PMID- 15441556
TI  - [Critical observations on Pean's gastroduodenal anastomosis. Treatment of
      following complications].

PMID- 15441557
TI  - [Physiological and morphological modifications of the striated muscle following
      intra-arterial injections of iodo-organic product into the humeral artery of the
      dog--experimental Volkmann's contracture].

PMID- 15441558
TI  - [Perforation of duodenal ulcer into the biliary ducts].

PMID- 15441559
TI  - [Broadened conception of the shock; local shock].

PMID- 15441560
TI  - [Vulvovaginitis due to Candida albicans].

PMID- 15441561
TI  - [The Soskin prostigmine test; 48 cases].

PMID- 15441562
TI  - [Diagnosis of clinically inapparent moles by systematic histological
      examination].

PMID- 15441563
TI  - [Technic of transfusion into the longitudinal sinus in the weak newborn].

PMID- 15441564
TI  - [The gemellary ovum].

PMID- 15441565
TI  - [Differentiation of anti-B iso-hemagglutinins].

PMID- 15441566
TI  - [Some aspects of the complexity of the blood groups, A B O].

PMID- 15441567
TI  - [Comprehensive study of the P blood factor].

PMID- 15441568
TI  - [The Rh antigen Eu].

PMID- 15441569
TI  - [The Du factor].

PMID- 15441570
TI  - [Correlation between the Lewis system and the secretor-nonsecretor system;
      research on 71 families].

PMID- 15441571
TI  - [A new case of anti-Fya in human serum].

PMID- 15441572
TI  - [Study of agglutinogen A3].

PMID- 15441573
TI  - [Blood groups ABO, MNS and Rh of Calicians, northwest Spain].

PMID- 15441574
TI  - [Distribution of Rh types in the Italian population].

PMID- 15441575
TI  - [Diagnostic value of Coombs' reaction in fetal and neonatal hemolytic disease].

PMID- 15441576
TI  - [Coombs' reaction; variations of the indirect reaction].

PMID- 15441577
TI  - [Experimental nuclear icterus].

PMID- 15441578
TI  - [Pathogenesis of hemolytic disease of the newborn, with special reference to the
      serologic mechanism of iso-immunization by A and B antigens].

PMID- 15441579
TI  - [Electronic microscope studies on hemolysis, agglutination, form and structure of
      erythrocytes].

PMID- 15441580
TI  - [Genetics in general and genetics of blood groups ABO, MN Pp].

PMID- 15441581
TI  - [Genetics of the Rh factors].

PMID- 15441582
TI  - [Serologic research on the anti-Rh immune antibodies].

PMID- 15441583
TI  - [Natural and acquired iso-agglutinins].

PMID- 15441584
TI  - [Blood groups in relation to anthropology].

PMID- 15441585
TI  - [Preparation of anti-M and anti-N test serums].

PMID- 15441586
TI  - [Preparation of test serums].

PMID- 15441587
TI  - [Erythroblastosis fetal].

PMID- 15441588
TI  - [Clinical, hematologic and serologic phenomena in the newborn affected by
      hemolytic disease due to Rh antagonism of the parents].

PMID- 15441589
TI  - [Technique of exchange transfusion].

PMID- 15441590
TI  - [Remarks on the clinical prognosis of hemolytic disease of the newborn treated by
      exchange transfusion].

PMID- 15441591
TI  - [Certain hematological aspects of hemolytic disease of the newborn].

PMID- 15441592
TI  - [Diaplacental permeability to Rh antibodies, and hemolytic disease].

PMID- 15441593
TI  - [The role of the placenta and other organs in hemolytic disease of the newborn
      caused by Rh antagonism].

PMID- 15441594
TI  - [Microscopic structure of the erythroblastic placenta].

PMID- 15441595
TI  - [Experimental and natural hemolytic diseases of newborn animals].

PMID- 15441596
TI  - [Role of the Dutch Red Cross in the field of blood transfusions].

PMID- 15441597
TI  - [Not Available].

PMID- 15441598
TI  - [True trachoma and hyperplastic tumors of the cornea].

PMID- 15441599
TI  - Failing sight caused by trachoma.

PMID- 15441600
TI  - [Suggested classification of trachoma].

PMID- 15441601
TI  - [Trachoma and blindness in South Africa].

PMID- 15441602
TI  - [Local treatment of trachoma with highly concentrated sulfamide drops].

PMID- 15441603
TI  - [Tonsillar physiopathology; clinical corollaries of the method of vital
      staining].

PMID- 15441604
TI  - [Chronic suppurative otitis media due to foreign bodies of the external auditory
      duct and eustachian tube].

PMID- 15441605
TI  - [Conservative surgery in sinusitis and its complications and local antibiotic
      chemotherapy].

PMID- 15441606
TI  - [Chordoma; 5 personnel cases].

PMID- 15441607
TI  - [Primary melanocarcinoma of the esophagus].

PMID- 15441608
TI  - [Two pharyngeal tumors of different localisations in the same patient].

PMID- 15441609
TI  - [Therapy of Meniere's vertigo].

PMID- 15441610
TI  - [Oto-rhino-laryngologic manifestations in cranial malformations].

PMID- 15441611
TI  - [Cervical spodylo-arthritis with compression of the spinal cord due to foreign
      bodies of the esophagus].

PMID- 15441612
TI  - [Osteomas of pericranial sinuses (frontal sinuses, ethmoid cells, sphenoid
      sinuses) diagnosis of cranio-facial bone tumors].

PMID- 15441613
TI  - [Double localisation of an esophageal cancer].

PMID- 15441614
TI  - [Pseudo-epitheliomatous form of syphilis of the base of the tongue].

PMID- 15441615
TI  - [Implantation of the ureters in the large intestine].

PMID- 15441616
TI  - [Pathogenesis and insulin therapy of simple diabetes mellitus of the adult].

PMID- 15441617
TI  - [Cyst formation contiguous to the renal pedicle and hypertension].

PMID- 15441618
TI  - [Results of the treatment of myocardial infarct by nicotinic acid compared to the
      results of the classic treatment; study of a few personal cases].

PMID- 15441619
TI  - [25th Anniversary of the Anti-Cancer Center of the University of Liege].

PMID- 15441620
TI  - [Significance of experimental cancer research].

PMID- 15441621
TI  - [Frequency of adenopathy secondary to skin cancer of the head and neck in
      relation to localization, surface extension and degree of infiltration].

PMID- 15441622
TI  - [Cancerization in vitro by chemical carcinogenic substances (polycyclic
      hydrocarbons)].

PMID- 15441623
TI  - [Distribution in the organism of radioactive colloidal gold 198 after
      intraperitoneal injection].

PMID- 15441624
TI  - [Disappearance threshold of diiodofluorescein from circulating blood].

PMID- 15441625
TI  - [Pseudo-pituitary syndromes].

PMID- 15441626
TI  - [The heart and the thyroid].

PMID- 15441627
TI  - [Present therapy of pulmonary tuberculosis].

PMID- 15441628
TI  - [Recent advances in the field of infectious disease and the antibiotics
      (chloromycetin, aureomycin)].

PMID- 15441629
TI  - [Treatment of chronic bronchopulmonary suppurations in the adult].

PMID- 15441630
TI  - [Mitral stenosis].

PMID- 15441631
TI  - [Not Available].

PMID- 15441632
TI  - [Present treatment of whooping cough].

PMID- 15441633
TI  - [Tuberculosis in children].

PMID- 15441634
TI  - [Relationship between alveolodental pyorrhea and general medicine].

PMID- 15441635
TI  - [Bacterial resistance to chemotherapeutic agents].

PMID- 15441636
TI  - [Appearance of tularemia in Belgium].

PMID- 15441637
TI  - [Not Available].

PMID- 15441638
TI  - [Granular cell tumors; myoblastomas, granulo-cellular rhabdomyomas;
      histiocytomas?].

PMID- 15441639
TI  - [Anisometropia].

PMID- 15441640
TI  - [Disorders of auriculo-ventricular conduction during typhoid fever].

PMID- 15441641
TI  - [Value of infiltrations and of resection of preaortic plexus in angina pectoris].

PMID- 15441642
TI  - [Artificial radioelements and their clinical use].

PMID- 15441643
TI  - [Cancer of the glans penis and of the cervix in husband and wife].

PMID- 15441644
TI  - [X-rays of diaphragmatic eventration and of diaphragmatic hernias].

PMID- 15441645
TI  - [Use of English ivy, Hedera helix L., in the treatment of whooping cough].

PMID- 15441646
TI  - [Fetid pleurisy cured by penicillin].

PMID- 15441647
TI  - [Contribution of bronchography to the study of non-tuberculous hemoptysis].

PMID- 15441648
TI  - [Purulent tuberculous pleurisy and streptomycin].

PMID- 15441649
TI  - [Case of hematocolpos].

PMID- 15441650
TI  - [Death from peritonitis after intestinal perforation by ascarids].

PMID- 15441651
TI  - [Essential nephrography, manifestation of hyperergia to iodine during intravenous
      urography].

PMID- 15441652
TI  - [Medical treatment of chronic degenerative rheumatism].

PMID- 15441653
TI  - [Indications for the surgical treatment of rheumatism].

PMID- 15441654
TI  - [Contrary effects of obstruction of a bronchial bifurcation].

PMID- 15441655
TI  - [Two cases of hemiplegia following blood transfusions].

PMID- 15441656
TI  - [Apoplectiform radial neuritis; absence of initial pain].

PMID- 15441657
TI  - [Case of spina ventosa in an adult cured by streptomycin].

PMID- 15441658
TI  - [Edmond de Reynier].

PMID- 15441659
TI  - [Three reminiscences of a country doctor].

PMID- 15441660
TI  - [Case of mixed tumor of the palatine region].

PMID- 15441662
TI  - [New perspectives in physiology].

PMID- 15441661
TI  - [Vagotomy by transthoracic route; evolution of surgical possibilities at
      Neuchatel].

PMID- 15441663
TI  - [The evolution of Biermer's anemia and its treatment].

PMID- 15441664
TI  - [Some clinical applications of hyaluronidase].

PMID- 15441665
TI  - [A medical law in force for over 170 years].

PMID- 15441666
TI  - [Repeated enterorrhagia in adults due to Meckel's diverticulum].

PMID- 15441667
TI  - [Hypertension and surgery].

PMID- 15441668
TI  - [Stomach resection for exclusion of inoperable gastroduodenal ulcers].

PMID- 15441669
TI  - [Mercurial stomatitis and necrotic osteitis caused by esidrone; pathogenesis and
      therapy].

PMID- 15441670
TI  - [Not Available].

PMID- 15441671
TI  - [Hepato-biliary vithormonotherapy].

PMID- 15441672
TI  - [Nervous disorders and hepatobiliary syndromes].

PMID- 15441673
TI  - [Methionine].

PMID- 15441674
TI  - [Serum esterases; hepatic origin and therapeutic role].

PMID- 15441675
TI  - [Nitrogen requirement in infectious disease and in surgery].

PMID- 15441676
TI  - [Diseases of the bile ducts except lithiasis and cancer].

PMID- 15441677
TI  - [Pathogenesis of gout].

PMID- 15441678
TI  - [Hepatic cirrhosis with chronic jaundice; clinical and biological problems
      concerning chronic jaundice; etiology and nosography of biliary cirrhosis;
      physiopathology of jaundice, splenomegaly, and pain].

PMID- 15441679
TI  - [Tetanic form of cholecystitis].

PMID- 15441680
TI  - [Organization and function of the cerebral cortex].

PMID- 15441681
TI  - [Affection manifested by diffused tetanoid contraction with variable hyperkinesia
      and of subacute fatal evolution].

PMID- 15441682
TI  - [Topectomy or subcortical incision of the areas 9-10-46 in mental disorders].

PMID- 15441683
TI  - [Novocain perfusion in postoperative complications of neurosurgery].

PMID- 15441684
TI  - [Diagnosis of secondary epithelioma of the brain by the presence of neoplastic
      cells in the cerebrospinal fluid].

PMID- 15441685
TI  - [Generalized fatal polyradiculoneuritis; cancerous meningitis and direct
      radicular infiltrations at the contact of affected meninges].

PMID- 15441686
TI  - [Bravais-Jackson's epilepsy of reflex appearance due to a hemispheric compression
      by a tumor].

PMID- 15441687
TI  - [Electroencephalograms and mental diseases].

PMID- 15441688
TI  - [Agraphia in a case of cranial trauma with lesion of the foot of the second and
      third left frontal convolutions].

PMID- 15441689
TI  - [Epilepsy; electroencephalographic localization and excision of the tumor under
      electrographic control; immediate cessation of crises].

PMID- 15441690
TI  - [Effect of prefrontal leucotomy on the behaviour of a maniac].

PMID- 15441691
TI  - [Algetic form of an undiagnosed syringomyelia].

PMID- 15441692
TI  - [Therapeutic research on tension accidents due to nerve injuries].

PMID- 15441693
TI  - [Dilation of chiasmal and protuberential cisterns in grave mental deficiency;
      importance of cisternotomy].

PMID- 15441694
TI  - [Triple contraction of the striated muscle and triple chronaxia of the muscle and
      its motor nerve].

PMID- 15441695
TI  - [Myoclonic progressive generalized epilepsy; clinical and bioelectrical study].

PMID- 15441696
TI  - [Disorders of respiratory rhythm with rhythmic and synchronous clonus of vocal
      cords and diaphragm; probable encephalic origin].

PMID- 15441697
TI  - [Cephalic unilateral tetanus of facial tonic hemispasm type; therapy and
      evolution].

PMID- 15441698
TI  - [Surgery of a right parietal meningioma; physiology of parietal lobe, pain and
      loss of sensitivity of parietal origin].

PMID- 15441699
TI  - [Phantom limb due to the resection of the axillary artery in a non-amputation
      case affected with total paralysis of the brachial plexus].

PMID- 15441700
TI  - [Minimal topectomy, cerebral biopsy].

PMID- 15441701
TI  - [Three cases of favourable results of surgery in intense blepharospasm; comments
      on paradoxal behavior of the orbicularis of the eyelids].

PMID- 15441702
TI  - [New apparatus in pneumoencephalography].

PMID- 15441703
TI  - [Craniopharyngioma in a woman aged 57; visual and auditive hallucinations; second
      report on the genesis of hallucinations occurring in cerebral lesions].

PMID- 15441704
TI  - [Ependymal tumors of the bone marrow and filum terminale].

PMID- 15441705
TI  - [Anatomico-clinical study of chronic anterior poliomyelitis].

PMID- 15441706
TI  - [Not Available].

PMID- 15441707
TI  - [Epileptic attacks provoked by intraventricular streptomycin injections].

PMID- 15441708
TI  - [Three case reports of Arnold-Chiari malformation].

PMID- 15441709
TI  - [Voluminous paraventricular angioma; complete excision].

PMID- 15441710
TI  - [Muscular balance in poliomyelitis and in peripheral paralysis; its objective
      representation].

PMID- 15441711
TI  - [Hemiplegia in a child following tonsillectomy].

PMID- 15441712
TI  - [Disorders of muscular tonus in spasmodic familial paraplegia].

PMID- 15441713
TI  - [Two cases of sporadic hypertrophic progressive neuritis of Dejerine-Sottas type
      with biopsy control].

PMID- 15441714
TI  - [Syndrome of lateral amyotrophic sclerosis probably of extenso-progressive
      nature].

PMID- 15441715
TI  - [Film demonstration of experimental allergic encephalomyelitis].

PMID- 15441716
TI  - [Large sylvian aneurysm].

PMID- 15441717
TI  - [Neurological manifestations of acute porphyria].

PMID- 15441718
TI  - [Two stereotype cases of tuberculoid leprosy from the same source, in Tahiti.
      Sensory-motor polyneuritis of the right half of the face and homolateral
      hypertrophy of the superficial cervical plexus].

PMID- 15441719
TI  - [Anatomico-clinical study of a case of spinal progressive amyotrophy (chronic
      anterior poliomyelitis].

PMID- 15441720
TI  - [Arteriovenous carotido-cavernous aneurysm].

PMID- 15441721
TI  - [Polyneuritic forms of porphyria of the saturnin type. Effect of cold on the
      elimination of porphyria. Favorable effect of an increased sugar diet. Study of
      several cases].

PMID- 15441722
TI  - [Prolonged evolution of Cushing's syndrome with large hypophyseal tumor].

PMID- 15441723
TI  - [Unilateral velo-pharyngo-laryngeal paralysis appearing simultaneously with a
      crural zona on same side].

PMID- 15441724
TI  - [Bilateral and asymmetric amyotrophic paralysis of periscapular muscles, with
      sudden and painful incipience].

PMID- 15441725
TI  - [A case of idiopathic porphyria accompanied by paralysis. Clinical data ten
      months after the incipience. Biochemical study].

PMID- 15441726
TI  - [Intracarotid novocaine emergency treatment of an epileptic seizure].

PMID- 15441727
TI  - [Symptomatic progress of an unrecognized disequilibration].

PMID- 15441728
TI  - [Case of hemiplegia caused by thrombosis of the internal carotid artery. Attempt
      of clinical synthesis].

PMID- 15441729
TI  - [Reconstruction of the ear].

PMID- 15441730
TI  - [Noma and penicillin therapy in Afghanistan].

PMID- 15441731
TI  - [Biopsy in stomatology].

PMID- 15441732
TI  - [Intra-dental granuloma].

PMID- 15441733
TI  - [Usefulness, inefficacy or harmfulness of sulfonamides and of penicillin in the
      treatment of osteo-cellulitis].

PMID- 15441735
TI  - [Modern casting technic].

PMID- 15441734
TI  - [Treatment of periapical lesions by drilling the canals].

PMID- 15441736
TI  - [Plastic crown inlays and post crowns].

PMID- 15441737
TI  - [Alginates; their physical and chemical properties].

PMID- 15441738
TI  - [Ney method in the design of clasps in partial prosthesis].

PMID- 15441739
TI  - [Neuro-thyroid correlations].

PMID- 15441740
TI  - [Usefulness of the knowledge of the morphology of the tooth for the cut of a
      jacket crown stump].

PMID- 15441741
TI  - [Acrylics and alveolar tissue].

PMID- 15441742
TI  - [Dental diagnosis in orthodontics].

PMID- 15441743
TI  - [Anatomic study of the sphenoid fissure; form, dimensions, position].

PMID- 15441744
TI  - [Intraspinal penicillin therapy in otogenous pneumococcic meningitis].

PMID- 15441745
TI  - [Unilateral papillary stasis in tumors of the frontal region and third
      ventricle].

PMID- 15441746
TI  - [Study of congenital malformations of the head].

PMID- 15441747
TI  - [Hemicraniosis (meningioma en plaque) with marked modifications of the eye
      fundus].

PMID- 15441748
TI  - [Intra-cranial injury due to shell fragments and late neuro-paralytic keratitis].

PMID- 15441750
TI  - [Syndrome of the carotid sinus].

PMID- 15441749
TI  - [Encephalitis in children with choroiditis; absence of intra-cranial
      calcifications].

PMID- 15441751
TI  - [Pseudo-tumoral regressive encephalitis during pregnancy].

PMID- 15441752
TI  - [Bulbo-protuberantial glioblastoma].

PMID- 15441753
TI  - [Fronto-callous glioblastoma, localized by arteriography].

PMID- 15441754
TI  - [Hyaline verrucosis of the papilla and modification of the visual field].

PMID- 15441755
TI  - [Acute Garcin's syndrome due to plasmocytoma of the cranial base].

PMID- 15441756
TI  - [Is injury of the optic nerve, diagnosed early following closed cranial trauma an
      indication for surgery].

PMID- 15441757
TI  - [Traumatic opto-chiasmatic arachnoiditis with optic atrophy and blindness in one
      eye and, two years later, reduction of visual acuity of the other eye; bilateral
      visual amelioration following encephalography and trepanation].

PMID- 15441758
TI  - [Acute meningoencephalitis caused by Pfeiffer bacilli complicating congestive
      otitis in an adult].

PMID- 15441759
TI  - [Facial symptomatic neuralgia in neurinoma of the pontocerebellar angle; surgery
      following vertebral arteriography; recovery following colibacillar meningitis].

PMID- 15441760
TI  - [Not Available].

PMID- 15441761
TI  - [Comparative pathology at the Congress of the Pacific Coast Section of the
      American Association for the Advancement of Science].

PMID- 15441762
TI  - [Treatment of arthritis by hormones extracted from Mexican Dioscorea].

PMID- 15441763
TI  - [Transfer of growth hormone from the normal parabion to the hypophysectomized
      parabion].

PMID- 15441764
TI  - [Q fever in northern California].

PMID- 15441765
TI  - [Statistical study of mortality at Ankara and Istanbul during the years 1940
      1944].

PMID- 15441766
TI  - [Muscular granulomas in domestic animals].

PMID- 15441767
TI  - [Administrative hygiene].

PMID- 15441768
TI  - [Air and the restorative power of sleep].

PMID- 15441769
TI  - [Not Available].

PMID- 15441770
TI  - [Reticulohistiocytic reaction in tuberculosis of domestic carnivores].

PMID- 15441771
TI  - [General considerations resulting from experiments with a dynamic supersonic
      aerosolyser].

PMID- 15441772
TI  - [Experimental treatment of chronic rhino-sinusitis in cats by streptomycin
      antagonist complexes].

PMID- 15441773
TI  - [Correlation between the calcium content of drinking water and endemic goiter
      occurrence].

PMID- 15441774
TI  - [Adrenal function tests in evolutive chronic polyarthritis].

PMID- 15441775
TI  - [Hyaluronic acid-hyaluronidase system and rheumatic disease].

PMID- 15441776
TI  - [Remarks and hypotheses on the role of vascular factors in the pathogenesis of
      arthroses and of coxarthrosis in particular; attempt at classification and
      pathogenic interpretation of hip-joint diseases].

PMID- 15441777
TI  - [Histogenesis of Paget's disease].

PMID- 15441778
TI  - [Evolution of calcifications of the supraspinatus tendon in periarthritis of the
      shoulder; recovery from calcifying tendinitis by spontaneous evacuation of the
      calcic deposit into the subdeltoid bursa].

PMID- 15441779
TI  - [Two cases of epiphyseal chondrodysplasia entering into the framework of
      Morquio's syndrome].

PMID- 15441780
TI  - [Negative therapeutic control in polyarthritis; the abuse of premature
      therapeutic publications].

PMID- 15441781
TI  - [Study of dechloruration in polyarthritis].

PMID- 15441782
TI  - [Different hypophyso-suprarenal treatments in P.C.E..].

PMID- 15441783
TI  - [Diffuse decalcifying osteosis and eunuchism].

PMID- 15441784
TI  - [Osteolysis of the scaphoid bone of the carpus; radiocarpal lesions in bakery
      workers].

PMID- 15441785
TI  - [Paget's disease with pelvic decalcification of unusual density].

PMID- 15441786
TI  - [Familial Paget's disease].

PMID- 15441787
TI  - [Brief encounter with English medicine].

PMID- 15441788
TI  - [Osteopathic medicine].

PMID- 15441789
TI  - [Presence of striped cutaneous dystrophies in patients with lumbar arthrosis].

PMID- 15441790
TI  - [Treatment of lumbo-sciatica by traction methods].

PMID- 15441791
TI  - [Bouillaud's disease; subacute articular rheumatism in adults].

PMID- 15441792
TI  - [Values of the nonsurgical treatment of lumbo-sciatica].

PMID- 15441793
TI  - [Vertebrotherapy table].

PMID- 15441794
TI  - [Use of vertebral tractions].

PMID- 15441795
TI  - [Portable table for cervical tractions].

PMID- 15441796
TI  - [A case of polyosteochondritis].

PMID- 15441797
TI  - [A case of olisthesic scoliosis caused by aplasia of a sacral articulation].

PMID- 15441798
TI  - [Early calcifications of chondro-costal cartilage in spondylarthritis
      ankylopoietica].

PMID- 15441799
TI  - [Treatment of diathetic rheumatism by sodium dehydrocholate].

PMID- 15441800
TI  - [Use of tetraethylammonium in pains of the shoulder].

PMID- 15441801
TI  - Elaboration in medicine.

PMID- 15441802
TI  - Cortisone therapy in rheumatoid arthritis.

PMID- 15441803
TI  - The months ahead.

PMID- 15441804
TI  - SWIMMER'S itch.

PMID- 15441805
TI  - The Providence Surgical Society.

PMID- 15441806
TI  - Diverticulitis and cancer of the colon.

PMID- 15441807
TI  - Industrial medicine and the private practitioner.

PMID- 15441808
TI  - The problems of general practice and their solutions.

PMID- 15441810
TI  - Medicine's concern about licensure of medical record librarians.

PMID- 15441809
TI  - Body fluids and the rationale of fluid therapy.

PMID- 15441811
TI  - CARE of hand injuries. IV. Lacerated wounds.

PMID- 15441812
TI  - [Affections of the synovial membranes of the hand].

PMID- 15441813
TI  - [Hand in gout].

PMID- 15441814
TI  - [Dupuytren's disease].

PMID- 15441815
TI  - [Hand in chronic inflammatory rheumatism].

PMID- 15441816
TI  - [Reaction to cadmium sulfate in current rheumatologic practice].

PMID- 15441817
TI  - [Surgical forms of non-tuberculous sacroiliac arthralgias and arthritis].

PMID- 15441818
TI  - [Indications of bronchoscopy in nontuberculous respiratory diseases].

PMID- 15441819
TI  - [Pre-erythrocytic and esoerythrocytic phases of the malaria parasite in man in
      the light of recent research].

PMID- 15441820
TI  - [Auscultatory anisosphygmia as an early indication of myocardial insufficiency].

PMID- 15441821
TI  - [Presence of antidiuretic elements in exudates and in urine, with particular
      reference to cirrhosis of the liver].

PMID- 15441822
TI  - [Pre-matrimonial prophylaxis and fitness for reproduction].

PMID- 15441823
TI  - [Blood sedimentation in leucemia].

PMID- 15441824
TI  - [Segmental bronchitis in children].

PMID- 15441825
TI  - [Preservation of bone transplants].

PMID- 15441826
TI  - [An unusual foreign body tolerated by the brain].

PMID- 15441827
TI  - [A rare splenohepatomegalic icterogenic syndrome due to hydatid cysts of the
      liver; treated with pneumoparacentesis by the Condorelli method].

PMID- 15441828
TI  - [The glycemic curve in electroshock].

PMID- 15441829
TI  - [Treatment of lymphocytic serositis with p-aminosalicylic acid; clinical
      observations].

PMID- 15441830
TI  - [Short history of sex hormones].

PMID- 15441831
TI  - [Hemorrhage factors in the exanthema of typhus].

PMID- 15441832
TI  - [Treatment of anuria].

PMID- 15441833
TI  - [Recurrent idiopathic phlebothrombosis].

PMID- 15441834
TI  - [Duodeno-biliary reflux].

PMID- 15441835
TI  - [Reaction to collargol in pulmonary tuberculosis].

PMID- 15441836
TI  - [Variations in the blood picture in lymphocytic serositis treated with p
      aminosalicylic acid].

PMID- 15441837
TI  - [Osteoma of the frontal sinus with ethmoidal, orbital and intracranial invasion].

PMID- 15441838
TI  - [Biliary syndromes of common bile duct and Vater's ampulla pathology].

PMID- 15441839
TI  - [Clinical physiopathology of venous circulation].

PMID- 15441840
TI  - [Chronic heredo-familial prehepatic non-hemolytic jaundice].

PMID- 15441841
TI  - [Retrograde abdominal aortography by the femoral route; experimental research].

PMID- 15441842
TI  - [Catheterization of the heart and angiocardiography in the diagnosis of
      congenital heart disease; technic and interpretation of results].

PMID- 15441843
TI  - [Pneumonectomy in suppurative and neoplastic diseases of the lung].

PMID- 15441844
TI  - [Blood changes in encephalo-facial neuroangiomatosis (Sturge-Weber disease)].

PMID- 15441845
TI  - [Treatment of arthropathies with desoxycorticosterone and ascorbic acid (Lewin
      and Wassen method); critical and analytical study; personal experience].

PMID- 15441846
TI  - [Study and interpretation of anemic syndromes of pregnancy].

PMID- 15441847
TI  - [Difference in action of various synthetic antihistamines with particular
      reference to exanthematic diseases of childhood].

PMID- 15441848
TI  - [Biological and clinical importance of hyaluronidase].

PMID- 15441849
TI  - [Recent acquisitions on heparin].

PMID- 15441850
TI  - [Aspects of typhoid of interest to surgery].

PMID- 15441851
TI  - [Abdominal perforations in course of typhoid].

PMID- 15441852
TI  - [Suppuration and osteomyelitis following typhoid-paratyphoid].

PMID- 15441853
TI  - [Histogenesis of pulmonary hamartoma].

PMID- 15441854
TI  - [Valvular hematic cysts of the adult; case].

PMID- 15441855
TI  - [A Krompecher basalioma of the mammary region].

PMID- 15441856
TI  - [Vascular modifications in a subject with phenomena of hypersensitivity].

PMID- 15441857
TI  - [Aneurysm of the pars membranacea septi; diverticulum of the septum
      membranaceum].

PMID- 15441858
TI  - [Correlations between transverse striation of muscle fiber and the laminae of
      rhythmic precipitation].

PMID- 15441859
TI  - [Metabolism of the nucleic acids in the spermatogenesis of Orthoptera
      (Acrididae)].

PMID- 15441860
TI  - [Effects of convulsions produced by electroshock on reconstructive processes].

PMID- 15441861
TI  - [Effects of convulsions caused by electroshock on the development of the
      genitalia and on the sexual activity of laboratory animals].

PMID- 15441862
TI  - [Effects of repeated convulsions produced by electroshock on the ovulation of the
      Columba domestica].

PMID- 15441863
TI  - [Consequences of destruction of the eye anlage on the development of the optic
      lobe in the chick embryo].

PMID- 15441864
TI  - [Brunner's organ in 10 species of acridioid Orthoptera].

PMID- 15441865
TI  - [Experimental anaphylactic and histaminic shock in the guinea pig;
      phenomenological differences revealed by the use of curare].

PMID- 15441866
TI  - [Behavior of -SH group substances in micro-organisms].

PMID- 15441867
TI  - [Biologic action of X-rays on the embryos of amphibians; transplantation
      experiments].

PMID- 15441868
TI  - [Functional disorders of the digestive system in microcythemic syndromes].

PMID- 15441869
TI  - [Etiopathogenesis and therapy of medullary insufficiency; casuistic
      contribution].

PMID- 15441870
TI  - [Clinical application of spirometry and of ergometry].

PMID- 15441871
TI  - [Significance of partial pressure of respiratory gas in the pulmonary alveoli and
      in arterial blood in respiratory function tests; research in pulmonary
      tuberculosis].

PMID- 15441872
TI  - [Presence of phlogogenic substance in the cerebrospinal fluid, with special
      reference to diseases of the nervous system of probable hyperergic pathogenesis].

PMID- 15441873
TI  - [Branch block with complete regression in a clinically normal person].

PMID- 15441874
TI  - [A new medicament in tuberculosis: benzoicthiocarbamide].

PMID- 15441875
TI  - [Concepts and limits of rheumatism].

PMID- 15441876
TI  - [Periarthritis of the shoulder, with special reference to etiopathogenesis].

PMID- 15441877
TI  - [Critical and experimental study on the relation between the function of the
      spleen and erythropoiesis].

PMID- 15441878
TI  - [Infections supervening in the course of streptomycin therapy of tuberculous
      meningitis].

PMID- 15441879
TI  - [Elements of child neuropsychology].

PMID- 15441880
TI  - [Clinical value of the thymol reaction (MacLagan reaction) in liver disease].

PMID- 15441881
TI  - [Clearance of bengal rose in liver function diagnosis].

PMID- 15441882
TI  - [Sideremic curve of the load of iron by mouth in dyspeptic subjects; latent
      tissue iron deficiency from reduced absorption].

PMID- 15441883
TI  - [Intestinal occlusion from Meckel's diverticulum].

PMID- 15441884
TI  - [Research on iron metabolism in liver disease. I. Acute liver disease and
      obstructive jaundice].

PMID- 15441885
TI  - [Late non-ulcerous mechanical stenosis in gastroenterostomy].

PMID- 15441886
TI  - [Emotional components in the genesis of cholecystalgia].

PMID- 15441887
TI  - [The hygienist in modern health organization].

PMID- 15441888
TI  - [Treatment of typhoid carriers with chloromycetin].

PMID- 15441889
TI  - [Q fever in San Marino].

PMID- 15441890
TI  - [Endemic brucellosis in the Province of Bologna].

PMID- 15441891
TI  - [Oenolism in Venice].

PMID- 15441892
TI  - [14th Century three-legged ischiopagus of the Hospital of Santa Maria della Scala
      at Florence].

PMID- 15441893
TI  - [Florentine physicians at the Battle of Montaperti, 1260].

PMID- 15441894
TI  - [Unpublished 14th century pharmaceutical herbal].

PMID- 15441895
TI  - [The antimalarial preferred by the Italians for half a century].

PMID- 15441896
TI  - [Origin of the cult of Asclepios in Rome and a medallion from the time of
      Antoninus Pius].

PMID- 15441897
TI  - [Necrology and medals of the Trieste physician Antonio Carlo Lorenzutti].

PMID- 15441898
TI  - [Lujo Thaller].

PMID- 15441899
TI  - [Prassitele Piccinini].

PMID- 15441900
TI  - [Aldo Mieli].

PMID- 15441901
TI  - [Stomatological alterations in a girl revealing a hemopathy which was present in
      latent and apparent form in the family].

PMID- 15441902
TI  - [The new Hruska system of radical surgery in treatment of periodontal diseases].

PMID- 15441903
TI  - [New method for determining the occlusion in bridgework].

PMID- 15441904
TI  - [Data and problems of malaria research].

PMID- 15441905
TI  - [Results of the study of anophelism in the province of Reggio Calabria].

PMID- 15441906
TI  - [Pontine Marshes and antimalarial drainage; technical premise and hygienic
      results of integral drainage].

PMID- 15441907
TI  - [Doctrine of the professional aptitude of aviators].

PMID- 15441908
TI  - [A flight at high altitude].

PMID- 15441909
TI  - [Velocity of the aortic sphygmic wave in man during normal respiration and in
      hypoxia].

PMID- 15441910
TI  - [Behavior of retinal angioscotoma in anoxia].

PMID- 15441911
TI  - [War and ocular diseases].

PMID- 15441912
TI  - [Alarm reaction and the general adaptation syndrome].

PMID- 15441913
TI  - [Progress in endocrinology].

PMID- 15441914
TI  - [Endocrine disease and hormone deficiency].

PMID- 15441915
TI  - [Cortisone, ACTH and joint disease].

PMID- 15441917
TI  - [Treatment of moderate pelvic deformities].

PMID- 15441916
TI  - [What every medical official should know about the atomic bomb].

PMID- 15441918
TI  - [Total blood proteins determined densimetrically, research on the protein formula
      (Kjeldhal-Howe method) following hemorrhage of obstetrical origin].

PMID- 15441919
TI  - [Conservative transperitoneal cesarean section with fistulization of the uterus
      in the treatment of septic dystocia].

PMID- 15441920
TI  - [War amenorrhea; amenorrhea of repatriated prisoners of German concentration
      camps].

PMID- 15441921
TI  - [Fecundity in women in rural districts of Treviso].

PMID- 15441922
TI  - [Treatment of cervicitis with local applications of Ecballium elaterium in pure
      powdered form and in oil].

PMID- 15441923
TI  - [Gravimetric of proteinemia, hemoglobinemia and hemocrit in obstetrics and in the
      newborn].

PMID- 15441924
TI  - [Pathogenesis and treatment of the so-called nephropathy of pregnancy].

PMID- 15441925
TI  - [The intermenstrual syndrome].

PMID- 15441926
TI  - [Analgesia in obstetrics; spinal anesthesia].

PMID- 15441927
TI  - [The premarital examination; useful, necessary, compulsory?].

PMID- 15441928
TI  - [The need for the revision of the rates for obstetric and gynecological
      services].

PMID- 15441929
TI  - [Functional dystocia and possible prevention].

PMID- 15441930
TI  - [Clinical and pathogenetic considerations of puerperal Simmond's disease].

PMID- 15441931
TI  - [Biochemistry of muscular fatigue in labor].

PMID- 15441932
TI  - [Use of norvalin in local treatment of infected vagino-vulvo-perineal solutions
      of continuity].

PMID- 15441933
TI  - [Intravenous use of spasmalgin in spastic states of the cervix in labor].

PMID- 15441934
TI  - [Heparin therapy in eclampsia and disease of the kidney in pregnancy].

PMID- 15441935
TI  - [Toxemia of pregnancy and histamines].

PMID- 15441936
TI  - [Present organization of auxiliary health personnel with special reference to
      obstetrics].

PMID- 15441937
TI  - [Use of synthetic antihistamines in experimental burns].

PMID- 15441938
TI  - [Splenectomy in the Banti syndrome; immediate and late results].

PMID- 15441940
TI  - [Shock as a clinical problem].

PMID- 15441939
TI  - [Desoxycorticosterone-ascorbic acid association in rheumatic diseases].

PMID- 15441941
TI  - [Allergic phenomena in burns].

PMID- 15441942
TI  - [Variations in blood cholesterin in experimental tetrachloroethane poisoning].

PMID- 15441943
TI  - [Pickworth-Fazio method applied to some portions of the digestive tract in
      gastroduodenal ulcer].

PMID- 15441944
TI  - [Histochemical research on pigment of the nerve cells of normal and pathologic
      sympathetic ganglia (endoarteritis obliterans; essential arterial hypertension].

PMID- 15441945
TI  - [Behavior of the megakaryocyte series in pernicious anemia].

PMID- 15441946
TI  - [Case of pharyngeal paralysis during diabetes].

PMID- 15441947
TI  - [Hepato-gastroenteric inflammatory syndrome treated intraduodenally with
      oxymethyl amide of nicotinic acid].

PMID- 15441948
TI  - [Clinical aspect and pathogenesis of the Plummer-Vinson syndrome].

PMID- 15441949
TI  - [Comparative observations on eosinophilia of the blood, secretions and tissues in
      allergic nasal disorders].

PMID- 15441950
TI  - [Action of blood transfusion on the parathyroidectomy syndrome].

PMID- 15441951
TI  - [Etiopathogenetic considerations in primary spinal cord necrosis].

PMID- 15441952
TI  - [Transitory hemiparetic and epileptic syndromes of diabetes mellitus].

PMID- 15441953
TI  - [Considerations on some patients "associated" for states of depression].

PMID- 15441954
TI  - [The routes of propagation to the nerve centers of substances injected into the
      meningeal spaces].

PMID- 15441955
TI  - [Hyperinsulinic hypoglycemia; a rare case of insular adenomatosis].

PMID- 15441956
TI  - [Recurrent malignant ganglioneuroma of the brain].

PMID- 15441957
TI  - [Oculogyric crises associated with paroxysmal bulimia in chronic encephalitis].

PMID- 15441958
TI  - [Action of vaccinal pyretotherapy in focal brain lesions probably of encephalitic
      origin].

PMID- 15441959
TI  - [Sudden spastic paraplegia due to occlusion of the abdominal aorta].

PMID- 15441960
TI  - [Electroshock in psychotics with pulmonary tuberculosis].

PMID- 15441962
TI  - [Rare clinical symptomatology of tumor of the corpus callosum].

PMID- 15441961
TI  - [Two cases of basilar impression].

PMID- 15441963
TI  - [A case of occipital intracranial hyperostosis with cerebellar symptoms].

PMID- 15441964
TI  - [Narcoanalysis].

PMID- 15441965
TI  - [Grave spinal cord syndrome following spinal anesthesia].

PMID- 15441966
TI  - [Intracranial localization of brain tumors without focal symptoms or with
      atypical symptoms].

PMID- 15441967
TI  - [Meteorological variations and epileptic attacks].

PMID- 15441969
TI  - [The so-called otohematoma of the insane].

PMID- 15441968
TI  - [Behavior of Velez' sign in therapeutic malaria].

PMID- 15441970
TI  - [Lombo-pubic electroshock in the treatment of nocturnal enuresis].

PMID- 15441971
TI  - [The central pathways of the cortex].

PMID- 15441972
TI  - [Cerebrospinal fluid in cerebral arteriosclerosis].

PMID- 15441973
TI  - [Choline therapy in psychasthenia].

PMID- 15441974
TI  - [Glycorrhachia and parkinsonian syndromes].

PMID- 15441975
TI  - [Behavior of the deep reflexes of the lower extremities after lumbar spinal
      anesthesia; contribution to the clinical differential diagnosis between intra and
      extramedullary tumors].

PMID- 15441976
TI  - [Pathological hunger in epilepsy].

PMID- 15441977
TI  - [Are the Schwann cells capable of granulopexic activity?].

PMID- 15441978
TI  - [The blood-cerebrospinal fluid ratio of urea hypobromite in nervous and mental
      disease].

PMID- 15441979
TI  - [Relations between schizophrenia and tuberculosis].

PMID- 15441980
TI  - [Action of malononitrile on the nervous system].

PMID- 15441981
TI  - [Mechanism of action of intravenous novocain].

PMID- 15441982
TI  - [Prognosis of polyneuritis].

PMID- 15441983
TI  - [Arterial pressure and ictus with hemiplegia].

PMID- 15441984
TI  - [A case of acute inferior-superior polioencephalitis].

PMID- 15441985
TI  - [Roussy-Levy disease].

PMID- 15441986
TI  - [Problems of inflammation of the axon].

PMID- 15441987
TI  - [Vagotomy in the treatment of peptic ulcer].

PMID- 15441988
TI  - [Unilateral cystic degeneration of the kidney].

PMID- 15441989
TI  - [Treatment of fractures of the humerus in children].

PMID- 15441990
TI  - [Surgical treatment of stricture of the urethra].

PMID- 15441991
TI  - [Not Available].

PMID- 15441992
TI  - [Not Available].

PMID- 15441993
TI  - [Developments in psychosurgery].

PMID- 15441994
TI  - [Evaluation of Moszkowicz's surgical method].

PMID- 15441995
TI  - [Nervous disorders in spontaneous occlusions of arteries of the extremities].

PMID- 15441996
TI  - [Simple drain for continued withdrawal of fluids].

PMID- 15441997
TI  - [Loewe-Rehn's method in plastic surgery].

PMID- 15441998
TI  - [Isolated fracture of the first rib during gymnastics].

PMID- 15441999
TI  - [Sequels of osteosynthesis by metallic prostheses by Kuntscher's method].

PMID- 15442000
TI  - [Independent neuralgia of the glossopharyngeal nerve treated by intracranial
      resection].

PMID- 15442001
TI  - [Bernou-Fruchaud's method of thoracoplasty].

PMID- 15442002
TI  - [Deodorization of hospital rooms].

PMID- 15442003
TI  - [Rehabilitation following injuries].

PMID- 15442004
TI  - [Epididymis teratoma with gynecomastia].

PMID- 15442005
TI  - [Chronic eosinophilic gastritis].

PMID- 15442006
TI  - [Facial hemangioma associated with chorioidealangioma and its relation to the
      Sturge-Weber disease].

PMID- 15442007
TI  - [Treatment of suppurative disease of fingers and hand in relation to the period
      of working inability].

PMID- 15442008
TI  - [Osteomyelosclerotic reticulosis with splenomegaly and myelemia].

PMID- 15442009
TI  - [Disorders of the blood composition in acute leukemias; biological and
      therapeutic study].

PMID- 15442010
TI  - [Attempt to differentiate the diverse varieties of acute leukemia by examination
      of fresh blood and bone marrow].

PMID- 15442011
TI  - [Blood groups of the population of Montpellier; distribution of the Rh antigen;
      high frequency of Rh negative subjects].

PMID- 15442012
TI  - [Acquired hemolytic jaundice with hematologic stigmata of congenital jaundice].

PMID- 15442013
TI  - [Method for the simultaneous estimation of the consumption of prothrombin in the
      clot and in the serum].

PMID- 15442014
TI  - [Reduction of Quick's prothrombin time in the plasma immediately before
      coagulation and in the serum immediately after].

PMID- 15442015
TI  - [Hemolytic macrocytic anemia due to splenic tuberculosis; diagnosis by puncture
      biopsy of the liver; splenectomy; cure].

PMID- 15442017
TI  - [Sternal puncture in hypochromic anemia due to ankylostomiasis].

PMID- 15442016
TI  - [Acute infantile leukosis with spasms of the glottis, Mikulicz' syndrome and
      icterus; evolution prolonged by exchange transfusion].

PMID- 15442018
TI  - [Incoagulable blood and Vaquez' disease].

PMID- 15442019
TI  - [New procedure for obtaining leukocytes, especially polynuclear circulating
      blood].

PMID- 15442020
TI  - [Formolgelification of blood].

PMID- 15442021
TI  - [Relative variation in the number of erythrocytes and leukocytes and in the
      percentage of polynuclears].

PMID- 15442022
TI  - [Sickle cell anemia in an Algerian].

PMID- 15442023
TI  - [Advantages of the Galli-Mainini test for the early diagnosis of pregnancy].

PMID- 15442024
TI  - [Precise and simple method for the titration of hemoagglutinins].

PMID- 15442025
TI  - [Behavior of the blood picture of the donor in repeated blood transfusions].

PMID- 15442026
TI  - [Transfusion of concentrated erythrocytes].

PMID- 15442027
TI  - [Modifications of retractility of coagulum in treatment with ultrasonics].

PMID- 15442028
TI  - [Diagnostic problem of rheumatic disease studied with the Mester reaction].

PMID- 15442029
TI  - [Laterality of thromboembolism of the brain].

PMID- 15442030
TI  - [Vital reactions].

PMID- 15442031
TI  - [Studies on adrenocorticotropic hormone].

PMID- 15442032
TI  - [Research in adrenocorticotropic hormone; determination by means of paper
      chromatography of the effect of ACTH on amino acids in urine and blood].

PMID- 15442033
TI  - [Determination of glutathione in the blood].

PMID- 15442034
TI  - [A method of treatment of rheumatism].

PMID- 15442035
TI  - [Spinal anesthesia].

PMID- 15442036
TI  - [Pedodontia].

PMID- 15442037
TI  - [Tuberculosis epidemic in a secondary school and the conclusions derived from
      it].

PMID- 15442038
TI  - [Anesthesia of the brachial plexus].

PMID- 15442039
TI  - [The 11-oxysteroids, the 17-ketosteroids, and the adrenocorticotropic hormone].

PMID- 15442040
TI  - [Cerebral abscess due to anaerobes].

PMID- 15442041
TI  - [Treatment of hyperchromic anemia].

PMID- 15442042
TI  - [Statistics of surgery for coxalgia: 1925-1950].

PMID- 15442043
TI  - [Contribution to the knowledge of man by the study of his behavior; mimetics and
      language].

PMID- 15442044
TI  - [Mass poisoning of sheep by sodium chlorate herbicide].

PMID- 15442045
TI  - [Infectious hepatitis in the dog (Rubarth's disease)].

PMID- 15442046
TI  - [Further studies of blood catalase in cattle artificially infected with foot-and
      mouth virus].

PMID- 15442047
TI  - [Hemostasis by epidural anesthesia and calcium; a problem in permeability].

PMID- 15442048
TI  - [Veterinary significance of the new contact insecticides].

PMID- 15442050
TI  - [Nomenclature, symptomatology and therapy of brucellosis; a comparative study of
      the disease in animal and in man].

PMID- 15442049
TI  - [Foot-and-mouth disease in Mexico].

PMID- 15442051
TI  - [Results of conservative methods of extraction of foreign bodies in cattle].

PMID- 15442052
TI  - [Streptotrichosis in the dog; case report].

PMID- 15442053
TI  - [Electric stunning of animals for slaughter with the Elther apparatus].

PMID- 15442054
TI  - [New, simple method of determining the specific gravity of small quantities of
      liquid].

PMID- 15442055
TI  - [Nomenclature, symptomatology and therapy of brucellosis; a comparative study of
      the disease in animal and in man].

PMID- 15442056
TI  - [Basic principles in the control and eradication of bovine tuberculosis;
      observations and experiences concerning Ostertag's method of tuberculosis control
      in Canton St. Gallen].

PMID- 15442057
TI  - [Directory of Swiss veterinarians].

PMID- 15442058
TI  - [Possibilities and limitations of clinical audiometry].

PMID- 15442059
TI  - [The myorenal syndrome].

PMID- 15442060
TI  - [Isotonic bath and alkaliplasma transfusion in the treatment of burns].

PMID- 15442061
TI  - [Preoperative care for dental surgery in the presence of hemorrhagic diathesis].

PMID- 15442062
TI  - [Prophylaxis of serum hepatitis; a flame-resistant lancet].

PMID- 15442063
TI  - [Predilection of physicians for the fine arts as hobbies; with general
      observations on the problem of professional deformation].

PMID- 15442064
TI  - [Lebrecht Widmer, 1861-1949].

PMID- 15442065
TI  - [New treatment of epithelioma, podophyllin therapy (peltacure)].

PMID- 15442066
TI  - [Experience with peridural anesthesia in obstetrics].

PMID- 15442067
TI  - [Ether narcosis in combination with relaxil].

PMID- 15442068
TI  - [Fate and preservation of male infants born in excess of female].

PMID- 15442069
TI  - [Problem of artificial insemination].

PMID- 15442070
TI  - [Comparative efficacy of different testosterone preparations].

PMID- 15442071
TI  - [Medicinal therapy of hypertension].

PMID- 15442072
TI  - [Indications and results in artificial insemination].

PMID- 15442073
TI  - [Pathogenesis of toxic hemolytic anemia following chronic phenacetin abuse].

PMID- 15442074
TI  - [Philosophical basis of normality in medicine].

PMID- 15442075
TI  - [Comparative study on the metabolic effects of ACTH and cortisone].

PMID- 15442076
TI  - [Sympathectomy and peptic ulcer].

PMID- 15442077
TI  - [Nonspecific therapy of inflammatory reactions].

PMID- 15442078
TI  - [Effect of rutin upon blood coagulation with reference to therapy and prophylaxis
      with dicumarol and its derivatives].

PMID- 15442079
TI  - [Philosophical basis of normality in medicine].

PMID- 15442080
TI  - [Electrophoretic examination of synovial exudates of the knee joint].

PMID- 15442081
TI  - [Myocarditis, myocardosis, myocardia].

PMID- 15442082
TI  - [Technic, indications and results in bronchography with a water-soluble, viscous
      contrast medium, joduron B].

PMID- 15442083
TI  - [Development of egressin, an oxyuricide].

PMID- 15442085
TI  - [Clinical test of egressin].

PMID- 15442084
TI  - [Pharmacology and toxicology of egressin].

PMID- 15442086
TI  - [Improvement in pediatric care from the point of view of public health].

PMID- 15442087
TI  - [Premature birth as a problem in world health].

PMID- 15442088
TI  - [Active immunization against infectious disease].

PMID- 15442089
TI  - [Amino acid metabolism].

PMID- 15442090
TI  - [Clinical role of potassium].

PMID- 15442091
TI  - [New aspects of renal pathology; chronic aminoaciduria; &c..].

PMID- 15442092
TI  - [Kidney function during first days of life].

PMID- 15442093
TI  - [Antivitamin action and its mechanism].

PMID- 15442094
TI  - [Pharmacology of vitamin D, with special reference to hypervitaminosis D].

PMID- 15442095
TI  - [Diseases of the adrenal cortex in children].

PMID- 15442096
TI  - [Eczema].

PMID- 15442097
TI  - [Congenital clubfoot].

PMID- 15442099
TI  - [Professional organization of Swiss physicians].

PMID- 15442098
TI  - [Acute infectious disease psychoses and schizophrenia in childhood].

PMID- 15442100
TI  - [Prefrontal leucotomy].

PMID- 15442101
TI  - [Results of investigations on the structure of urinary calculi from the Near
      East].

PMID- 15442102
TI  - [Myocardosis in liver cirrhosis].

PMID- 15442103
TI  - [Angiocardiopneumography in diagnosis of pulmonary and mediastinal tumors].

PMID- 15442104
TI  - [Observations on phonocardiography].

PMID- 15442105
TI  - [Paper-chromatographic analysis of human gastric secretion].

PMID- 15442106
TI  - [Treatment of distal radio-ulnar dislocation].

PMID- 15442107
TI  - [Pathologic granulations of leukocytes in pulmonary tuberculosis].

PMID- 15442108
TI  - [Modifications of the bronchus caused by tuberculous lymph nodes and their
      significance for the course of tuberculosis in children].

PMID- 15442109
TI  - [Critical observations on chemotherapeutic tamponade of pulmonary cavities].

PMID- 15442110
TI  - [Permeation of the placenta by penicillin].

PMID- 15442111
TI  - [Effect of hydrated ergot alkaloids upon carbohydrate metabolism].

PMID- 15442112
TI  - [Re-expansion of the lung following partial pneumonectomy].

PMID- 15442113
TI  - [Treatment of essential enuresis in the adult with lumbopubic electro shock].

PMID- 15442114
TI  - [Standardization of technic and nomenclature of precordial leads in
      electrocardiography].

PMID- 15442115
TI  - [Simple treatment of certain forms of obesity].

PMID- 15442116
TI  - [Experimental study of a new hemostatic, sodium -naphthylamine-4-sulfonate,
      naphthionine].

PMID- 15442117
TI  - [Notes on treatment of rheumatism].

PMID- 15442118
TI  - [Tetanus and curare].

PMID- 15442119
TI  - [Alfred Brunner on his 60th birthday].

PMID- 15442120
TI  - [Observations on the technic of extrapleural pneumolysis].

PMID- 15442121
TI  - [Supplementary pneumolysis].

PMID- 15442122
TI  - [Treatment of pulmonary tuberculosis complicated by bronchiectasis].

PMID- 15442123
TI  - [Successful decortication of the lung in tuberculosis].

PMID- 15442124
TI  - [Prophylaxis and therapy of postoperative pulmonary atelectasis].

PMID- 15442125
TI  - [Oxygen saturation of arterial blood following pneumonectomy].

PMID- 15442126
TI  - [Idiopathic mega-esophagus].

PMID- 15442127
TI  - [Diagnosis of tumors of the thymus].

PMID- 15442128
TI  - [Operative treatment of traumatic diaphragmatic hernia].

PMID- 15442129
TI  - [Value of the sacral approach in surgery of the pelvis minor].

PMID- 15442130
TI  - [Experiences and observations on surgical therapy of rectal carcinoma].

PMID- 15442131
TI  - [Treatment of infiltrating tumors of the bladder].

PMID- 15442132
TI  - [Androgen therapy of advanced cancer of the breast].

PMID- 15442133
TI  - [Experiences with the surgical and conservative therapy of distal closed spiral
      fractures of the leg].

PMID- 15442134
TI  - [Primary cutaneous transplantation in open fractures, particularly of the leg].

PMID- 15442135
TI  - [Surgery of the acromioclavicular joint].

PMID- 15442136
TI  - [Posttraumatic osteolysis of the extremity of the clavicle].

PMID- 15442137
TI  - [Experimental penicillin-controlled osteoplasty in osteomyelitis].

PMID- 15442138
TI  - [Streptomycin therapy of osteoarticular tuberculosis].

PMID- 15442139
TI  - [Epidural spinal abscess].

PMID- 15442140
TI  - [Spina bifida and accident].

PMID- 15442141
TI  - [Observations on sero- and anatoxin prophylaxis of tetanus].

PMID- 15442142
TI  - [Use of narcosynthesis for admission of guilt].

PMID- 15442143
TI  - [Complications of Q-fever].

PMID- 15442144
TI  - [Effect of pituitary implant upon osteomyelopathy with agranulocytosis].

PMID- 15442145
TI  - [Use of BAL in diffuse parenchymal disease of the liver].

PMID- 15442146
TI  - [Antiphlogistic effect of pyrazols, especially of irgapyrin, in peroral and
      parenteral administration].

PMID- 15442147
TI  - [Conduction anesthesia with xylocaine].

PMID- 15442148
TI  - [The excision gastroscope; a new attachment for taking biopsy sections with the
      gastroscope].

PMID- 15442149
TI  - [Critical study of microradiography, with special reference to its possible use
      in dentistry].

PMID- 15442150
TI  - [A classic case of acromegaly; comparative paradental observations].

PMID- 15442151
TI  - [Detachable stereoscopic magnifying glass with face mask as an aid in surgical
      and other professional examinations and procedures].

PMID- 15442152
TI  - [Treatment of noma].

PMID- 15442154
TI  - [Nomenclature in the medical sciences].

PMID- 15442153
TI  - [Unusual complications in wisdom tooth eruption; extraction during inflammation].

PMID- 15442155
TI  - [An external and internal examination; reflexions after 25 years of private
      practice].

PMID- 15442156
TI  - [Nitrous oxide and its effect on the nerve cells].

PMID- 15442157
TI  - [National medicine and dentistry in the United States].

PMID- 15442158
TI  - [Lead-holder for use in fitting crown rings].

PMID- 15442159
TI  - [Consideration of the exceptional status of the teeth in relation to other
      organs, and conclusions drawn therefrom; a study of dental deterioration from the
      viewpoint of the whole organism, and a scientific explanation made with the aid
      of two new concepts].

PMID- 15442160
TI  - [Etiology of dens in dente].

PMID- 15442161
TI  - [Fluorine, fillings, desensitization and protective layer].

PMID- 15442162
TI  - [Grafts in plastic and reparative surgery].

PMID- 15442163
TI  - [Hruska's new radical surgical therapy of paradentosis].

PMID- 15442164
TI  - [Facial neuralgias].

PMID- 15442165
TI  - [Paul Guillermin on his 70th birthday].

PMID- 15442166
TI  - [Painless dentistry].

PMID- 15442167
TI  - [Prof. Dr. Bernhard Gottlieb].

PMID- 15442168
TI  - [Studies in the technic of dental and maxillary tomography].

PMID- 15442169
TI  - [Plastic surgery of the mandible with steel wire and a roentgenographic study of
      its results].

PMID- 15442170
TI  - [Beginnings of the Swiss ARPA (Association for the Study of Paradentopathy)].

PMID- 15442171
TI  - [Recementing a post crown].

PMID- 15442172
TI  - [Gold crowns with acrylic facings].

PMID- 15442173
TI  - [Alfred Gysi on his 85th birthday, 31 August 1950].

PMID- 15442174
TI  - [Allergy in stomatology].

PMID- 15442175
TI  - [The maturation factor].

PMID- 15442176
TI  - [The teeth as an object of comparative research in biology].

PMID- 15442177
TI  - [Anesthesia and analgesia with nitrous oxide].

PMID- 15442178
TI  - [Penicillin and severe wounds of the maxillo-facial region].

PMID- 15442179
TI  - [The profile and full prosthesis; esthetic, physiologic and pathologic aspects].

PMID- 15442180
TI  - [Harmonia dentium. (Latin for: Balanced dentition.)].

PMID- 15442181
TI  - [Esthetic aspects of prosthetics].

PMID- 15442183
TI  - [Operative-orthodontic treatment of cuspid retention].

PMID- 15442182
TI  - [Etiology of the retention and extrusion of the cuspids].

PMID- 15442184
TI  - [Extraction of the impacted upper cuspid].

PMID- 15442185
TI  - [Methods of determining the exact position of retained teeth].

PMID- 15442186
TI  - [Practical experiences with a root canal filler of artificial resin].

PMID- 15442187
TI  - [Mesiodistal clasps in construction of the partial prosthesis].

PMID- 15442188
TI  - [SL (sulfonamide), a new chemotherapeutic for use in dentistry and surgery].

PMID- 15442189
TI  - [Raising the bite by means of a prosthesis].

PMID- 15442190
TI  - [Esthetics of the partial prosthesis].

PMID- 15442191
TI  - [Simple method for better casting].

PMID- 15442192
TI  - [Two uses for the crown excavator].

PMID- 15442193
TI  - Pair production and photoelectric effect in scintillation phosphors.

PMID- 15442194
TI  - Phagocytosis during bacteremia in mice: a preliminary report.

PMID- 15442195
TI  - A method for collecting and sterilizing large numbers of Drosophila eggs.

PMID- 15442196
TI  - Theory of the electrodeposition of metals from aqueous solutions.

PMID- 15442197
TI  - An assay method for the behavioral effects of L-glutamic acid.

PMID- 15442198
TI  - The recombination coefficient for the F layer.

PMID- 15442199
TI  - Lipid interrelationship in health and in coronary artery disease.

PMID- 15442200
TI  - Inhibition of anaphylaxis in guinea pigs by D-catechin.

PMID- 15442201
TI  - Regeneration of the shoot apex of Lupinus albus after operations upon the central
      initials.

PMID- 15442202
TI  - Studies in edema: cholesterol and its relation to protein nitrogen in edema
      fluid.

PMID- 15442203
TI  - The urea complexes of unsaturated fatty acids.

PMID- 15442204
TI  - An ideal preparation for dissection of spinal, peripheral, and autonomic nerves
      of the rat.

PMID- 15442205
TI  - Fibrinolytic activity of purified thrombin.

PMID- 15442206
TI  - Central mechanisms for recovery of neuromuscular function.

PMID- 15442207
TI  - A collaborative genetical survey of the human populations of the Pacific area.

PMID- 15442208
TI  - The concept of "internal compensation".

PMID- 15442209
TI  - ZOOLOGICAL nomenclature; basic issues in the controversy on zoological
      nomenclature.

PMID- 15442210
TI  - Control of precipitation from cumulus clouds by various seeding techniques.

PMID- 15442211
TI  - The electron microscopy of sectioned nerve.

PMID- 15442213
TI  - Sanitary seal for infrared microcells.

PMID- 15442212
TI  - Studies on pituitary adrenocorticotropin.

PMID- 15442214
TI  - Electromagnetic enrichment of Fe58 content and concurrent impoverishment of Fe54
      content in iron.

PMID- 15442215
TI  - The eosinophil response: immediate vs. delayed eosinopenia.

PMID- 15442216
TI  - Centrifugation as an aid in examining and fixing rotifers.

PMID- 15442217
TI  - A comparison of meteor activity with occurrence of sporadic E reflections.

PMID- 15442218
TI  - Polymers from chicle.

PMID- 15442219
TI  - Several effects of maleic hydrazide on plants.

PMID- 15442220
TI  - A new microculture slide.

PMID- 15442221
TI  - Absorption and translocation of radioactive 2,4-DI by bean plants as affected by
      cosolvents and surface agents.

PMID- 15442222
TI  - Effect of bacterial polysaccharide on cell divisio.

PMID- 15442223
TI  - Amino acids in high and low protein corn.

PMID- 15442224
TI  - Role of the earth sciences in general education.

PMID- 15442225
TI  - Compounds capable of plant amylase inhibition.

PMID- 15442226
TI  - Discovery of early cretaceous mammals and frogs in Texas.

PMID- 15442227
TI  - Arctic ice drift and the Humboldt current.

PMID- 15442228
TI  - Reaction time of the common housefly (Musca domestica).

PMID- 15442230
TI  - Physics research at T. R. E.

PMID- 15442229
TI  - I. Q. and month of birth.

PMID- 15442231
TI  - William Jackson Humphreys.

PMID- 15442232
TI  - A simple micromanipulator.

PMID- 15442233
TI  - A new streptomycin.

PMID- 15442234
TI  - The relation in man between cholesterol levels in the diet and in the blood.

PMID- 15442235
TI  - Effect of density and average atomic number of the medium on the counting yield
      of beta and gamma radiation in a solution-type Geiger counter.

PMID- 15442236
TI  - The curarelike effect of thiamine hydrochloride solution on vagal inhibition of
      the frog heart.

PMID- 15442237
TI  - On the existence of bonds between ossein and inorganic bone fraction.

PMID- 15442238
TI  - Brucella Ring Test antigen prepared by reduction of a tetrazolium salt.

PMID- 15442239
TI  - Protection of mice against x-radiation by thiourea.

PMID- 15442240
TI  - Fluorescence of mixtures of arterenol, epinephrine, and phosphate.

PMID- 15442241
TI  - Biotin deficiency as the causative agent of induced cryptorchidism in albino
      rats.

PMID- 15442242
TI  - The civil liberties of scientists report.

PMID- 15442243
TI  - On political oaths and affidavits.

PMID- 15442244
TI  - The toxicity of ammonia.

PMID- 15442245
TI  - Hydrostatic pressure reversal of narcosis in tadpoles.

PMID- 15442246
TI  - Pancreatic changes after injection of intermediary fat metabolites.

PMID- 15442248
TI  - Dr. Mills' rejoinder.

PMID- 15442247
TI  - The Donora episode--a reply to Clarence A. Mills.

PMID- 15442249
TI  - Proposed uniform endings for names of higher categories in zoological
      systematics.

PMID- 15442250
TI  - Astrochemical problems in the formation of the earth.

PMID- 15442251
TI  - August Krogh: 1874-1949.

PMID- 15442252
TI  - A limitation on the ultracentrifuge separation-cell technique.

PMID- 15442253
TI  - Germaniferous lignite from the District of Columbia and vicinity.

PMID- 15442254
TI  - Rapid carbon dioxide test for sickling.

PMID- 15442255
TI  - To what extent is oxygen uptake of the intact embryo related to that of its
      homogenate?

PMID- 15442256
TI  - Effect of zinc deficiency on the synthesis of tryptophan by Neurospora extracts.

PMID- 15442257
TI  - Vitamin P protection against radiation.

PMID- 15442258
TI  - Likelihood of photorespiration or light-inhibited respiration in green plants.

PMID- 15442259
TI  - Enzymic conversion of maltose into unfermentable carbohydrate.

PMID- 15442260
TI  - Activation of arginase in vitro by mouse carcass extract and the cobalt ion.

PMID- 15442261
TI  - Further study of the role of hyaluronidase in the fertilization of rabbit ova in
      vivo.

PMID- 15442262
TI  - A simple staining technique for detecting virus diseases in some woody plants.

PMID- 15442263
TI  - Biological experiments on Drosophila melanogaster with supersonic vibrations.

PMID- 15442264
TI  - A simplified method of lyophilizing microorganisms.

PMID- 15442265
TI  - Planchets for radioactive material.

PMID- 15442266
TI  - Note on the freezing point of citrate solutions used in the dilution of bull's
      semen.

PMID- 15442267
TI  - A simple method for opening quartz capsules containing radioactive materials.

PMID- 15442268
TI  - Water-soluble riboflavin derivative.

PMID- 15442269
TI  - Foreign publications in the field of organic chemistry.

PMID- 15442270
TI  - Use of dried hemoglobin in the assay of pepsin.

PMID- 15442271
TI  - Manpower for research and development.

PMID- 15442272
TI  - A radiation meter for disaster use.

PMID- 15442273
TI  - Cross tolerances in resistant houseflies.

PMID- 15442274
TI  - A semiautomatic injection apparatus for use with radioactive solutions.

PMID- 15442275
TI  - The informational capacity of the human ear.

PMID- 15442276
TI  - The effect of aureomycin on Endamoeba histolytica in vitro.

PMID- 15442277
TI  - Precipitation of menstrual bleeding in monkeys by a folic acid antagonist.

PMID- 15442278
TI  - Fat deposits in the kidney in chronic intoxication of the dog by
      hexachlorocyclohexane.

PMID- 15442279
TI  - A simple apparatus for multiple uniform intravenous injections.

PMID- 15442280
TI  - Plasma concentrations of p-aminosalicylic acid increased by p-(di-n
      propylsulfamyl) benzoic acid.

PMID- 15442281
TI  - The composition of Meconium; isolation of blood-group-specific polysaccharides;
      abnormal compositions of meconium in meconium ileus.

PMID- 15442282
TI  - Taste reactions to antithyroid substances.

PMID- 15442283
TI  - Cellular opacity and the activity of chloroplast pigments in photo-synthesis.

PMID- 15442284
TI  - Concerning the measurement of pH, ion activities, and membrane potentials in
      colloidal systems.

PMID- 15442285
TI  - Chemical composition of the vitelline membrane of Ascaris lumbricoides var. suis.

PMID- 15442286
TI  - Effect of trace minerals on growth and fattening of swine.

PMID- 15442287
TI  - Evidence of a homing instinct in the Bermuda spiny lobster.

PMID- 15442288
TI  - Acetaldehyde accumulation in excised wheat roots induced by plant growth
      substances.

PMID- 15442289
TI  - Antimycin A, an antibiotic with insecticidal and miticidal properties.

PMID- 15442290
TI  - The solubility of fibrin clots produced by thrombin and by snake venom.

PMID- 15442291
TI  - Effect of evisceration on renal glycogen.

PMID- 15442292
TI  - The effect of exercise upon the lethality.

PMID- 15442293
TI  - Adaptive production of amylase and lipase by three species of fungi.

PMID- 15442294
TI  - Determination of circulating red cell volume by radioactive chromium.

PMID- 15442295
TI  - Failure of vitamin B12 to promote growth of premature infants.

PMID- 15442296
TI  - Effect of tricaine methanesulfonate on the determination of sulfonamides.

PMID- 15442297
TI  - Use of blood groups in human classification.

PMID- 15442298
TI  - Nitrogen fixation by the green and purple sulfur bacteria.

PMID- 15442299
TI  - Windowless, flow type, proportional counter for counting C14.

PMID- 15442300
TI  - Preliminary report on a device for the objective measurement of the negative
      afterimage phenomenon.

PMID- 15442301
TI  - A preliminary investigation of the relationship between visual fusion of
      intermittent light and intelligence.

PMID- 15442302
TI  - Studies on the mechanism of nitrate assimilation in neurospora.

PMID- 15442303
TI  - A new hemolytic agent for the manometric determination of the oxygen content of
      blood.

PMID- 15442304
TI  - Radioautographs of frog membrane.

PMID- 15442305
TI  - Action of bacterial toxins on the "fragility" of chicken erythrocytes.

PMID- 15442306
TI  - Adaptation to caloric restriction.

PMID- 15442307
TI  - Nucleodepolymerase activity of precancerous rat liver.

PMID- 15442308
TI  - Determination of DDT by bioassay.

PMID- 15442309
TI  - Tyrosinase in human skin: demonstration of its presence and of its role in human
      melanin formation.

PMID- 15442310
TI  - Zinc precipitation of plasmin.

PMID- 15442311
TI  - A simple technique for observing carotid and brachial artery pulse.

PMID- 15442312
TI  - Cretaceous rocks in the Kamishak Bay area, Cook Inlet, Alaska.

PMID- 15442313
TI  - Lower Cretaceous rocks at Cape Kaguyak north of Kukak Bay, Alaska.

PMID- 15442314
TI  - Measurement of ion migration on paper in an electric field. Transference numbers
      of nickel and copper sulfates.

PMID- 15442315
TI  - Penetration of benzpyrene into the stomach wall of mouse.

PMID- 15442316
TI  - Oxygen consumption and radiophosphate uptake by minced brain from mice of
      different ages in relation to propagation of mouse encephalomyelitis virus.

PMID- 15442317
TI  - Problems in statistical analyses of geophysical time series.

PMID- 15442318
TI  - A. E. V. Richardson, 1883-1949.

PMID- 15442319
TI  - The influence of glutamic acid on test performance.

PMID- 15442320
TI  - The measurement of radioactive hydrogen in solid samples-comparison with gas
      counting.

PMID- 15442321
TI  - A maternal influence on the incorporation of methionine into liver protein.

PMID- 15442322
TI  - Phenylhydrazine oxalate as "trapping agent" for the simultaneous fixation of
      intermediate products in lactic acid fermentation with living cells.

PMID- 15442323
TI  - The experimental feeding of parathion to dairy cows.

PMID- 15442324
TI  - A rational method for calculating colloid osmotic pressure of serum.

PMID- 15442325
TI  - Decreased "hunger" but increased food intake resulting from hypothalamic lesions.

PMID- 15442326
TI  - "Funginert"--a designation for inherently fungus-resistant material.

PMID- 15442327
TI  - [Cat scratch disease].

PMID- 15442328
TI  - [Acute hemolytic anemia caused in infants by the administration of large doses of
      phenylsemicarbazide].

PMID- 15442329
TI  - [Twenty-six cases of surgery for "blue babies"].

PMID- 15442330
TI  - [Disturbances of consciousness and generalized muscular hypotonia in infantile
      paralysis].

PMID- 15442331
TI  - [General infection due to Bacillus pyocyaneus (Pseudomonas aeruginosa) in
      infants; 12 cases].

PMID- 15442332
TI  - [Anoxia].

PMID- 15442333
TI  - [Clinical, biological and histological comparisons in some liver diseases].

PMID- 15442335
TI  - [Mediastinal lipomas].

PMID- 15442334
TI  - [Metabolic disorders and hypopigmentation in phenylpyruvic oligophrenia].

PMID- 15442336
TI  - [Jaundice due to satellite hepatitis revealing a chronic cholecystitis, non
      lithiasic at first, unnoticed during an exploratory laparotomy and discovered by
      biliary radiomanometry].

PMID- 15442337
TI  - [Pathology of noise in flying].

PMID- 15442338
TI  - [The physiologic action of cortisone and A.C.T.H..].

PMID- 15442339
TI  - [Medical books of the 16th century at the Library of the Faculty of Medicine of
      Paris].

PMID- 15442340
TI  - [Ocular complications of infantile and juvenile diabetes].

PMID- 15442341
TI  - [Mental and affective development of the diabetic child].

PMID- 15442343
TI  - [The French Association of Diabetics].

PMID- 15442342
TI  - [Statistical inquiry on diabetes in the medical region of Paris].

PMID- 15442344
TI  - [Streptococcic bacteriology and rheumatism].

PMID- 15442345
TI  - [Pernicious malaria unrecognized in repatriated colonials].

PMID- 15442346
TI  - [Typho-paratyphoid encephalitis; preeminent role of toxin].

PMID- 15442347
TI  - [First attempts at treatment of typhoid infections with chloromycetin in
      Indochina].

PMID- 15442348
TI  - [Latent forms of amebiasis; their importance in medicine and in particular in
      hematology].

PMID- 15442349
TI  - [The liver in malaria; studied in 45 cases by means of biopsy].

PMID- 15442351
TI  - [The physiology of sweating].

PMID- 15442350
TI  - [Malaria and diguanyl].

PMID- 15442352
TI  - [Some rare alopecias].

PMID- 15442353
TI  - [Bone marrow blood correlations in hematoderma and in particular in
      granulomatosis].

PMID- 15442354
TI  - [Two cases of Darier-Ferrand fibrosarcoma].

PMID- 15442355
TI  - [Psychosomatic analysis of some dermatoses, particularly eczema].

PMID- 15442357
TI  - [Acute articular rheumatism].

PMID- 15442356
TI  - [Lentiginosis and digestive polyposis; Peutz' syndrome].

PMID- 15442358
TI  - [Minimum calcium balance; technic and results in urinary lithiasis, tumorous
      calcinosis and in certain osteoarticular disorders].

PMID- 15442359
TI  - [The abdominal route in the surgical treatment of recto-sigmoid neoplasms].

PMID- 15442360
TI  - [Sciatica of the nerve trunk and nerve root; statistics on 1,000 operated cases].

PMID- 15442361
TI  - [Vertebral angioma with spinal cord compression; cure by radiotherapy].

PMID- 15442362
TI  - [Genital fibroma and prolapse; surgical therapy].

PMID- 15442363
TI  - [The Andre Cretin operation; surgical treatment of chronic rheumatism].

PMID- 15442364
TI  - [Present ideas on treatment of mega-esophagus].

PMID- 15442365
TI  - [A simple instantaneous liver test capable of reflecting the functional state of
      the liver in diffuse parenchymatous attacks].

PMID- 15442366
TI  - [An instantaneous liver test in different circumstances of hepatological
      practice].

PMID- 15442367
TI  - [Flocculation reactions in minor hepato-biliary states; the MacLagan, Hanger,
      Gros and Wunderly tests].

PMID- 15442368
TI  - [Kernicterus].

PMID- 15442369
TI  - [Prenatal and natal influences, and the influences of the first days of life].

PMID- 15442370
TI  - [New ideas on the development of the infant and the later psychological
      repercussions].

PMID- 15442372
TI  - [Study of the school-age child].

PMID- 15442371
TI  - [The pre-school child].

PMID- 15442373
TI  - [Present ideas on psychic disorders of adolescence and on juvenile delinquency].

PMID- 15442374
TI  - [School and conflict].

PMID- 15442375
TI  - [Repercussions of institutionalization on the psychomotor development of young
      children].

PMID- 15442376
TI  - [Environment and familial neurosis].

PMID- 15442377
TI  - [Psychoneurotic and psycho-physiologic reactions to occupational environment].

PMID- 15442378
TI  - [Neuroses and behavior disorders in the adult in their preventive aspects].

PMID- 15442379
TI  - [Problems of adaptation to the menopause].

PMID- 15442380
TI  - [Psychotherapy of the second half of life according to C.H. Jung].

PMID- 15442381
TI  - [Problems of adaptation during old age].

PMID- 15442382
TI  - [Breast feeding].

PMID- 15442383
TI  - [Action of delta-5-pregnenolone in evolutive polyarthritis].

PMID- 15442384
TI  - [Antibacterial action of neomycin and furadroxyl in vitro and in vivo].

PMID- 15442385
TI  - [Indications, technics and results of ligation of the inferior vena cava in 55
      cases of uncompensated cardiopathy].

PMID- 15442386
TI  - [Anesthesia in uncompensated cardiopathy treated by ligation of the inferior vena
      cava].

PMID- 15442387
TI  - [Ten cases of stenosis of the aortic isthmus operated on successfully].

PMID- 15442389
TI  - [Acroparesthesia, acroparesthalgia].

PMID- 15442388
TI  - [Complications and pre- and postoperative care in ligation of the inferior vena
      cava for cardiac insufficiency].

PMID- 15442390
TI  - [Bornholm's disease or epidemic myalgia].

PMID- 15442391
TI  - [Continuous electrocardiography during intra-cardiac catheterization].

PMID- 15442392
TI  - [Aging of serums].

PMID- 15442393
TI  - [Compound F in the urine of steroid diabetics].

PMID- 15442394
TI  - [Osseous tumors of Paget].

PMID- 15442395
TI  - [Classification of focal endothoracic suppurations; principals, results,
      mechanism of action of treatment by precise endobronchial penicillin therapy].

PMID- 15442396
TI  - [Cardiac malformation without cyanosis in mother and child].

PMID- 15442397
TI  - [Critical study of the splenomegaly syndrome with hemorrhages of the digestive
      tract in the child].

PMID- 15442398
TI  - [Adenopathy during chronic hepatitis with jaundice].

PMID- 15442399
TI  - [Epilepsy due to tumors of the temporal lobe; 72 anatomo-clinical observations].

PMID- 15442400
TI  - [Sexual differentiations and distribution of fat].

PMID- 15442401
TI  - [Auricular flutter in the child].

PMID- 15442402
TI  - [Present state of chemotherapy, by P.A.S., of experimental tuberculosis in the
      guinea pig].

PMID- 15442403
TI  - [Treatment of acute mercury poisoning with BAL].

PMID- 15442404
TI  - [Antiulcer extracts taken from the gastrointestinal mucosa and the urine].

PMID- 15442405
TI  - [Convulsions of the infant].

PMID- 15442406
TI  - [Collective conflict states; psycho-physiologic reaction to the work
      environment].

PMID- 15442407
TI  - [Disk sciatica and its diagnosis by myelography with sodium mono-iodo-methane
      sulfonate; 100 cases].

PMID- 15442408
TI  - [Cutaneous absorption of estrogens].

PMID- 15442409
TI  - [Utilization of French frogs for the biologic diagnosis of pregnancy].

PMID- 15442410
TI  - [Anthropometric scheme applied to endocrinology; the masculine morphotype].

PMID- 15442411
TI  - [Morphological variations among normal men].

PMID- 15442412
TI  - [The evolution of the morphogram during adolescence].

PMID- 15442413
TI  - [The female morphotype].

PMID- 15442414
TI  - [Anthropometric aspects of eunochoidism in both sexes].

PMID- 15442415
TI  - [Anthropometric aspects of feminism in man].

PMID- 15442417
TI  - [Study of the sequels of 420 cases of phlebitis].

PMID- 15442416
TI  - [Anthropometric aspects of virilism in women].

PMID- 15442418
TI  - [Physiology of female sex hormones].

PMID- 15442419
TI  - [Studies on grippe in pediatrics; Hirst's reaction; reaction of cold agglutinins;
      atypical influenzal pneumonia].

PMID- 15442420
TI  - [Hirst's reaction; its biological interpretation in the child and the infant].

PMID- 15442421
TI  - [Cold agglutinins; their clinical significance; their biological importance in
      primitive atypical virus pneumonias].

PMID- 15442422
TI  - [Atypical influenzal pneumonia].

PMID- 15442423
TI  - [Biologic diagnosis of grippe in the infectious pathology of the infant; results
      of 70 Hirst reactions].

PMID- 15442424
TI  - [Influenza in the infant; study of a small epidemic from December 1949 to January
      1950 identified by Hirst's reaction, 29 cases].

PMID- 15442425
TI  - [Malignant visceral lupus erythematosus].

PMID- 15442426
TI  - [Surgical treatment of retrodeviations of the uterus].

PMID- 15442427
TI  - [Myomectomy in France in the treatment of fibromas; its historical evolution; its
      possibilities and limits; polymyomectomies].

PMID- 15442428
TI  - [Obstetrical consequences of uterine curettage].

PMID- 15442429
TI  - [Use of curare in obstetrics].

PMID- 15442430
TI  - [Four cases of gastroduodenal ulcers cured clinically and radiologically by
      endothoracoscopic splanchnicectomy].

PMID- 15442431
TI  - [Forty cases of rectal cancer treated by the Babcock method].

PMID- 15442432
TI  - [Cardiac resuscitation].

PMID- 15442433
TI  - [Electroencephalography; introduction].

PMID- 15442434
TI  - [Electroencephalographic signs of tumors of the hemispheres].

PMID- 15442435
TI  - [Pathologic rhythms detected at a distance from the tumors of the cerebral
      hemispheres].

PMID- 15442436
TI  - [Radiologic control of the localizations made by electroencephalography].

PMID- 15442437
TI  - [Causes of error in the localization of tumors of the hemispheres].

PMID- 15442438
TI  - [Electroencephalography in a series of 38 tumors of the posterior fossa].

PMID- 15442439
TI  - [Activation of electroencephalograms by scopolamine-chloralose].

PMID- 15442440
TI  - [Sleep as activator of electroencephalograms in epilepsy of the child].

PMID- 15442441
TI  - [Electrical activity of the brain of the newborn infant].

PMID- 15442442
TI  - [Electrical stimulation of the brain in neurosurgery].

PMID- 15442443
TI  - [Coxsackie virus].

PMID- 15442444
TI  - [Treatment of syphilis in the U.S..].

PMID- 15442445
TI  - [Surgical treatment of coxarthritis].

PMID- 15442446
TI  - [Sciatic neuralgia].

PMID- 15442447
TI  - [Pathology of the cervical disks].

PMID- 15442449
TI  - [Dorsal and lumbar neuralgias].

PMID- 15442448
TI  - [Cervico-brachial neuralgia].

PMID- 15442450
TI  - [Crenotherapy of chronic rheumatism].

PMID- 15442451
TI  - [Experimental vectography].

PMID- 15442452
TI  - [Spontaneous hematomas of the rectus abdominis].

PMID- 15442453
TI  - [Clinical significance of gynecomastia; a case of gynecomastia due to
      desoxycorticosterone treatment].

PMID- 15442454
TI  - [Some aspects of the genetics of micro-organisms].

PMID- 15442455
TI  - [Endocrine rheumatisms].

PMID- 15442456
TI  - [Pneumoperitoneum in the treatment of pulmonary tuberculosis].

PMID- 15442457
TI  - [Treatment of peri-laryngeal cancer by radium puncture; median thyro-hyotomy].

PMID- 15442458
TI  - [Treatment of cicatricial stenosis of the larynx by surgical excision and
      placement of an endo-laryngeal prosthesis of synthetic resin (acrylic)].

PMID- 15442459
TI  - [The problem of buccal electro-galvanism].

PMID- 15442461
TI  - [Osseous reticulosis].

PMID- 15442460
TI  - [Abscess of the lingual tonsil].

PMID- 15442462
TI  - [Note on the cochlear toxic action of dihydrostreptomycin].

PMID- 15442463
TI  - [Results of treatment of hemolytic disease of the newborn by exchange
      transfusion, followed up in 1949 by the Centre Regional de Transfusion of Lille].

PMID- 15442464
TI  - [Late anemias of the newborn; role of breast feeding].

PMID- 15442465
TI  - [Grave jaundice of newborn due to maternal iso-immunization to the rhesus
      factor].

PMID- 15442466
TI  - [Evaluation of the effect of stilboestrol in the treatment of malignant tumors].

PMID- 15442467
TI  - [Cellulalgia].

PMID- 15442468
TI  - [Testicular insufficiency].

PMID- 15442469
TI  - [Surgical treatment of spontaneous or traumatic intracerebral hemorrhages].

PMID- 15442470
TI  - [The problem of non-traumatic iridocyclitis].

PMID- 15442472
TI  - [Periarthritis and pathology of the tendons].

PMID- 15442471
TI  - [Physio-pathological study of influenzal respiratory infections in the infant].

PMID- 15442473
TI  - [Some recent applications of angiography].

PMID- 15442474
TI  - [Cytologic diagnosis of cancer in biologic fluids and secretions].

PMID- 15442475
TI  - [Chronic evolutive polyarthritis and the pituitary-adrenal system].

PMID- 15442476
TI  - [Diet in pregnancy and lactation].

PMID- 15442477
TI  - [Primary splenic neutropenia and hypersplenism; critical study].

PMID- 15442478
TI  - [Passive anti-A1 immunization of A2 subjects by transfusion; practical importance
      of the idea of passive iso-immunization].

PMID- 15442479
TI  - [New orientation in the interpretation of the etiology and pathogenesis of
      certain congenital ocular diseases].

PMID- 15442480
TI  - [Acute segmental edema of the small intestine; a peculiar clinical form of serous
      apoplexy].

PMID- 15442481
TI  - [Treatment of whooping cough with aureomycin].

PMID- 15442482
TI  - [Hemolytic action of tetanus toxin].

PMID- 15442483
TI  - [Symphysiotomy of Zarate; my impressions yesterday and today].

PMID- 15442484
TI  - [Puberty and allergy].

PMID- 15442485
TI  - [Academic radiology and integral survey radiology].

PMID- 15442486
TI  - [A new American trypanosomiasis in Argentina; finding of Trypanosoma rangeli
      (Tejera, 1920) in man and dog].

PMID- 15442487
TI  - [Reasons for amplifying the courses of the Municipal School of Blood
      Transfusion].

PMID- 15442488
TI  - [Seminar of pathology, clinical medicine and surgical technic].

PMID- 15442489
TI  - [Electroshock in bronchial asthma].

PMID- 15442490
TI  - [Treatment of chronic adnexitis by penicillin-novocain infiltrations].

PMID- 15442491
TI  - [Early and late serological results of treatments made exclusively with bismuth
      in recently acquired syphilis].

PMID- 15442492
TI  - [Pseudopolyneuritic amyotrophic lateral sclerosis (Marie-Patrikios type)].

PMID- 15442493
TI  - [Primary tuberculous conjunctivitis with fistulized submaxillary adenopathies;
      treatment with general and local streptomycin].

PMID- 15442494
TI  - [Seminar of pathology, clinical medicine and surgical technic].

PMID- 15442495
TI  - [Quinine; toxicological study; personal observations].

PMID- 15442496
TI  - [Conduct and management of labor].

PMID- 15442497
TI  - [Phlebitis migrans and neoplasms].

PMID- 15442498
TI  - [Treatment of passive homosexuals].

PMID- 15442499
TI  - [Model clinical history for the gynecological service].

PMID- 15442500
TI  - [Seminar of pathology, clinical medicine and surgical technic; bronchiectasis and
      its treatment].

PMID- 15442501
TI  - [History of medicine].

PMID- 15442502
TI  - [Case of cancer of the sigmoid].

PMID- 15442503
TI  - [Thyroid and tuberculosis].

PMID- 15442504
TI  - [Treatment of rheumatic fever with rutin and ascorbic acid].

PMID- 15442505
TI  - [Climacteric and allergy].

PMID- 15442506
TI  - [Brucellosis].

PMID- 15442507
TI  - [Cancer of the sigmoid; Hartmann operation (resection and invagination of the
      rectal end and definitive colostomy)].

PMID- 15442508
TI  - [Cushing syndrome].

PMID- 15442509
TI  - [Cushing syndrome; clinical aspect].

PMID- 15442510
TI  - [Etiological diagnosis and etiological (anticryptogamic fungicide) treatment of
      cancer].

PMID- 15442511
TI  - [Oxygen in post-operative treatment].

PMID- 15442512
TI  - [Health education in the factory].

PMID- 15442513
TI  - [Cushing syndrome; anatomical lesions].

PMID- 15442514
TI  - [Seminar of pathology, clinical medicine and surgical technic; a case of
      pleurisy].

PMID- 15442515
TI  - [Prognosis for subsequent pregnancy in cesarean section by modern technic].

PMID- 15442516
TI  - [Electron microscope research on the morphology of Vibrio cholerae].

PMID- 15442517
TI  - [Benign chondroblastoma].

PMID- 15442518
TI  - [Retroperitoneal tumor in an infant; teratoma].

PMID- 15442519
TI  - [Cushing syndrome; etiopathogenesis].

PMID- 15442520
TI  - [Seminar of pathology, clinical medicine and surgical technic; collaboration of
      plastic surgery and psychosomatic medicine; facial wrinkles].

PMID- 15442521
TI  - [Seminar of pathology, clinical medicine and surgical technic; accidental
      ingestion of caustic soda by a child].

PMID- 15442522
TI  - [Actinomycosic mycetoma in Argentina].

PMID- 15442523
TI  - [Etiologic diagnosis and etiologic (anticryptogamic fungicide) treatment of
      cancer].

PMID- 15442524
TI  - [Miliary pulmonary carcinosis].

PMID- 15442525
TI  - [Cushing syndrome; clinical diagnosis].

PMID- 15442526
TI  - [Seminar of pathology, clinical medicine and surgical technic; Miles operation of
      descent operation?].

PMID- 15442527
TI  - [Indications of prefrontal lobotomy in treatment of pain].

PMID- 15442528
TI  - [Arturo Ameghino].

PMID- 15442529
TI  - [Our position on rheumatic diseases; rheumatological uniformity; classification].

PMID- 15442530
TI  - [Carcinoma of the fallopian tubes; a case with uterine metastasis].

PMID- 15442532
TI  - [Cushing syndrome; radiological diagnosis].

PMID- 15442531
TI  - [New vehicles in dermatological therapy].

PMID- 15442533
TI  - [Seminar of pathology, clinical medicine and surgical technic; paralytic ileus in
      the postoperative period of appendectomy].

PMID- 15442534
TI  - [Radiology in acute abdomen].

PMID- 15442535
TI  - [Mal perforant and sympathicolumbar ganglionectomy].

PMID- 15442536
TI  - [Persistent diarrhea in a vagotomized patient].

PMID- 15442537
TI  - [Serous cyst of the kidney].

PMID- 15442538
TI  - [Anorectal fistula; tubular fistulectomy].

PMID- 15442539
TI  - [Cushing syndrome; hormone diagnosis].

PMID- 15442540
TI  - [First International Congress of Internal Medicine; preliminary program, Paris,
      11-14 September, 1950].

PMID- 15442541
TI  - [Industrial medicine is a true medical specialty].

PMID- 15442542
TI  - [Medico-social problems in gynecology].

PMID- 15442543
TI  - [Problems of hospital organization in the United States].

PMID- 15442544
TI  - [International sanitary regulations and the maritime aspects of venereal disease
      control].

PMID- 15442545
TI  - [Sickness insurance systems in the United States].

PMID- 15442546
TI  - [Problems of hospital organization in the United States].

PMID- 15442547
TI  - [Social insurance in agriculture].

PMID- 15442548
TI  - [Evolution of social security and family welfare in the United States].

PMID- 15442549
TI  - [International comparison of hospital statistics].

PMID- 15442550
TI  - [Legal problems arising from the intervention of the social worker].

PMID- 15442551
TI  - [Venereal disease control in the U.S..].

PMID- 15442552
TI  - [For the improvement of neo-natal statistics].

PMID- 15442553
TI  - [Vaccination against tetanus].

PMID- 15442554
TI  - [General regulation of labor in communities of the mentally deficients].

PMID- 15442555
TI  - [United Nations Educational, Scientific and Cultural Organization; declaration of
      the experts on questions of race].

PMID- 15442557
TI  - [Louis Portes].

PMID- 15442556
TI  - [Professor Louis Portes, Chairman of the National Order of Physicians, a member
      of the Academy of Medicine; (1891-1950)].

PMID- 15442558
TI  - [Medical secrecy].

PMID- 15442559
TI  - [Immunization against diphtheria].

PMID- 15442560
TI  - [Personal income tax; fiscal situation of medical analysis laboratories].

PMID- 15442561
TI  - [Study on sanitation].

PMID- 15442562
TI  - [Reimbursement for maternity expenses and secrecy of confinement].

PMID- 15442563
TI  - [Report of the work of the first session of the Committee of Experts on Rabies].

PMID- 15442564
TI  - [Evolution and cost of alcoholism in France from 1938 to 1948].

PMID- 15442565
TI  - [Brain of alcoholics].

PMID- 15442567
TI  - [Serological reactions with trepogen in leprosy].

PMID- 15442566
TI  - [Penicillin therapy of trachoma].

PMID- 15442568
TI  - [Dermatosis caused by p-aminosalicylic acid].

PMID- 15442569
TI  - [Favorable results of conservative treatment (fibula for tibia) in a case of
      total right and partial left agenesia of the tibia].

PMID- 15442570
TI  - [Medical views on the purity of the water supply].

PMID- 15442571
TI  - [Rh subtypes and their value in determination of paternity].

PMID- 15442572
TI  - [Function of the adrenals in schizophrenia].

PMID- 15442573
TI  - [English and Scotch].

PMID- 15442574
TI  - [Rh subtypes and their value in determination of paternity].

PMID- 15442575
TI  - [Decease in the mortality rate of certain diseases during the period 1931-1945].

PMID- 15442576
TI  - [Alcohol consumption and disease due to alcoholism in France; notes from a study
      trip to Paris in 1949].

PMID- 15442577
TI  - Heterotopic ossification in the cavity wall of a uterus.

PMID- 15442578
TI  - [Hairpin in the bladder].

PMID- 15442579
TI  - UNDER the influence of narcotic drugs; in the Supreme Court of South Africa; Rex
      vs. Dr. P. Douglas-Henry.

PMID- 15442581
TI  - Catheterization of the natural openings of the antrum of Highmore.

PMID- 15442580
TI  - The teaching of anaesthesia to interns.

PMID- 15442582
TI  - Tick-borne relapsing fever on the Witwatersrand gold mines; its treatment with
      aureomycin.

PMID- 15442583
TI  - Urinary infections in general practice.

PMID- 15442584
TI  - Abdominal trauma.

PMID- 15442585
TI  - Murine typhus; its pathology.

PMID- 15442586
TI  - Right bundle-branch-block and the wolff-Parkinson-White syndrome.

PMID- 15442587
TI  - A case of radio-opaque bile without cholecystography.

PMID- 15442588
TI  - Tuberculosis of Meckel's diverticulum.

PMID- 15442589
TI  - Physiology of micturition and ejaculation.

PMID- 15442590
TI  - Myocardial infarction; some indications in prognosis.

PMID- 15442591
TI  - Massive resection of small gut, report of a case.

PMID- 15442592
TI  - Solitary diverticulitis of the caecum.

PMID- 15442593
TI  - Medical aspects of road safety.

PMID- 15442594
TI  - IN MEMORIAM Alexander Daniel Edington, B.Sc., F.R.C.P.E.

PMID- 15442595
TI  - Psychosomatic factors in dermatology.

PMID- 15442596
TI  - Infantile hemiplegia treated by removal of one cerebral hemisphere.

PMID- 15442597
TI  - Kemithal sodium; a preliminary clinical study.

PMID- 15442598
TI  - Ischiorectal abscess and related suppuration.

PMID- 15442599
TI  - Procedures in the control of tuberculosis. The practical approach: 1. Nursing in
      tuberculosis; the use of nurse aides.

PMID- 15442600
TI  - EXCESSIVE or extortionate fees; memorandum on Section 80 of the Medical Dental
      and Pharmacy Act.

PMID- 15442601
TI  - Cancer of the breast; the scope of irradiation.

PMID- 15442602
TI  - Progress in the study of the modes of action of the human uterus during pregnancy
      and labour.

PMID- 15442603
TI  - Procedures in the control of tuberculosis; the practical approach: 2.
      Hospitalization.

PMID- 15442604
TI  - Acute haemolytic disease of the newborn, erythroblastosis foetalis.

PMID- 15442605
TI  - Observations of the general incidence of certain signs usually connected with
      thyrotoxicosis, with special reference to 'lid lag', (von Graefe's sign).

PMID- 15442606
TI  - Biological testing of milk for tuberculosis and brucellosis.

PMID- 15442607
TI  - Procedures in the control of tuberculosis; the practical approach: 3. The role of
      the settlement in tuberculosis control.

PMID- 15442608
TI  - The dietary calcium requirements of man.

PMID- 15442609
TI  - The genesis of neurosis, an objective account.

PMID- 15442610
TI  - Procedures in the control of tuberculosis; the practical approach: 4. Diagnosis
      and treatment.

PMID- 15442611
TI  - Anticoagulants in surgery; the clinical application.

PMID- 15442612
TI  - Perineal prostatectomy.

PMID- 15442613
TI  - A consideration of recent surgery of osteoarthritis of the hip joint.

PMID- 15442614
TI  - Procedures in the control of tuberculosis; the practical approach; the action
      front.

PMID- 15442615
TI  - Sarcomatous changes in myomas of the uterus; a clinical study of 21 cases.

PMID- 15442616
TI  - Pruritus ani.

PMID- 15442617
TI  - Ventricular tachycardia; report of a fatal case.

PMID- 15442618
TI  - "Why do my patients leave me?".

PMID- 15442619
TI  - Ectopic pregnancy.

PMID- 15442620
TI  - Chemosurgical treatment of external cancer: a microscopically controlled method
      of excision.

PMID- 15442621
TI  - Female pelvic surgery; when is it necessary?

PMID- 15442622
TI  - CARE of hand injuries.

PMID- 15442623
TI  - Doctor, your special interests are showing.

PMID- 15442624
TI  - Radioactive isotopes and their use in medicine.

PMID- 15442625
TI  - Newer therapeutic agents.

PMID- 15442627
TI  - Radiologic treatment of tumors of the thorax.

PMID- 15442628
TI  - Recent development in the field of insecticides.

PMID- 15442626
TI  - Bladder tumors; their diagnosis, treatment and prognosis.

PMID- 15442629
TI  - TRANSACTIONS of the South Dakota State Medical Association; sixty-ninth annual
      session Huron, South Dakota May 21-23, 1950.

PMID- 15442630
TI  - SOUTH Dakota Medical Association roster, 1950; membership by districts.

PMID- 15442631
TI  - Present day concepts of antibiotic therapy.

PMID- 15442632
TI  - The antibiotics and their mechanism of action.

PMID- 15442634
TI  - The value of good history-taking in medical diagnosis.

PMID- 15442633
TI  - Economic factors in precipitating psychiatric disorders.

PMID- 15442635
TI  - Obstetric hemorrhage.

PMID- 15442636
TI  - The management of the third stage of labor.

PMID- 15442637
TI  - Clinical experience with dromoran hydrobromide (Nu 2206) for the relief of
      chronic pain.

PMID- 15442638
TI  - [Rehabilitation of invalids of World War II].

PMID- 15442639
TI  - [Pathogenesis of hypertension; clinical aspect].

PMID- 15442640
TI  - [A method of complex balneotherapy].

PMID- 15442641
TI  - [Treatment of gastro-intestinal diseases in the health center on Lake
      Medvezhe'e].

PMID- 15442642
TI  - [Active and inactive form of tuberculosis].

PMID- 15442643
TI  - [Selection of pulmonary tuberculous patients for climatic sanatoria of northern
      Caucasus].

PMID- 15442644
TI  - [Hydrosulfide baths treatment of circulatory disorders].

PMID- 15442645
TI  - [Treatment of hypertonic diseases in the Kislovod health resort].

PMID- 15442646
TI  - [A new type of oscillograph].

PMID- 15442647
TI  - [Treatment of certain diseases of the nervous system in the health resort Liubin
      Velikii].

PMID- 15442648
TI  - [Ulcers of lower extremities treated by means of balneotherapy].

PMID- 15442649
TI  - [Functional uterine hemorrhages and their therapy].

PMID- 15442651
TI  - [Clinical application of the root Panax ginseng].

PMID- 15442650
TI  - [Physiologic fluctuation of erythrocyte sedimentation rate].

PMID- 15442652
TI  - [Artificial pneumoperitoneum in treatment of pulmonary tuberculosis].

PMID- 15442653
TI  - [Phthisiotherapeutist A. A. Ostroumov].

PMID- 15442654
TI  - [Aspiration pneumonia in pulmonary hemorrhage in tuberculosis].

PMID- 15442655
TI  - [Bronchial tuberculosis as a early form of a pulmonary process].

PMID- 15442656
TI  - [Importance of rare tubercle bacilli in the diagnosis of pulmonary tuberculosis].

PMID- 15442657
TI  - [Differential diagnosis of tuberculous pneumonia].

PMID- 15442658
TI  - [Remote results in streptomycin therapy of tuberculous meningitis in children].

PMID- 15442659
TI  - [Classification of silicosis and siliko-tuberculosis].

PMID- 15442660
TI  - [Pulmonary tuberculosis in middle- and old age].

PMID- 15442661
TI  - [Treatment of pulmonary tuberculosis in sanatoria in hot weather].

PMID- 15442662
TI  - [Five cases of fractures of the sternum].

PMID- 15442663
TI  - [Surgical section of diaphragmatic nerve in pulmonary tuberculosis].

PMID- 15442664
TI  - [Apparatus for the treatment of knee dislocation in tuberculous gonitis in
      children].

PMID- 15442665
TI  - [Pernicious anemia in pregnancy].

PMID- 15442666
TI  - [Extraction of shell fragment from the upper lobe of the right lung].

PMID- 15442667
TI  - [Postoperative complications in ascaridosis].

PMID- 15442668
TI  - [Fluorography, roentgenoscopy roentgenography].

PMID- 15442669
TI  - [Control of cancer in the Soviet Union].

PMID- 15442670
TI  - [Causes of late diagnosis of cancer of the stomach].

PMID- 15442671
TI  - [Contrast and combination of gastroscopic and roentgenographic investigations in
      cancer of the stomach].

PMID- 15442672
TI  - [Method of roentgenographic diagnosis of cancer of the lungs].

PMID- 15442673
TI  - [Cancer of the mammary gland].

PMID- 15442674
TI  - [Role of the preventive examination in early diagnosis of cancer of the cervix
      uteri].

PMID- 15442675
TI  - [New views in regard to etiology, diagnosis and treatment of actinomycosis].

PMID- 15442676
TI  - [Echinococcal diseases].

PMID- 15442677
TI  - [Trachoma and its control].

PMID- 15442678
TI  - [Clinical aspects, diagnosis and surgical treatment of echinococcus cysticus of
      the liver].

PMID- 15442680
TI  - [Scientific methods of prophylaxis and immunization of the organism].

PMID- 15442679
TI  - [Treatment by implantation of the thyroid gland by the Filatov method].

PMID- 15442681
TI  - [Case of foreign body in the brain, brought by the blood stream].

PMID- 15442682
TI  - [Studies on the reactions following gunshot wounds].

PMID- 15442683
TI  - [Treatment of taeniasis with the extract of Cucurbitaceae seed].

PMID- 15442684
TI  - [Organization of first aid in collective farms].

PMID- 15442685
TI  - [Prevention of tuberculosis in rural areas].

PMID- 15442686
TI  - [Mikhail Georgievich Kurlov].

PMID- 15442687
TI  - [M. A. Nivinskii, a pioneer of experimental oncology].

PMID- 15442688
TI  - [History of military-field therapy in Russia].

PMID- 15442689
TI  - [Rheumatic injuries of the heart in children].

PMID- 15442690
TI  - [Small doses of adrenalin as a hypotensive medium in hypertonia].

PMID- 15442691
TI  - [Blood transfusion into the innominate bone].

PMID- 15442692
TI  - [Effect of blood transfusion on renal function].

PMID- 15442693
TI  - [Atrioventricular heart block in typhoid and paratyphoid].

PMID- 15442694
TI  - [Oscillography as an objective method of determination of local vascular
      disorders following cooling off].

PMID- 15442695
TI  - [Effect of nicotinic acid in bronchial asthma].

PMID- 15442696
TI  - [Case of multiple myeloma].

PMID- 15442697
TI  - [Poisoning with plasmodicide].

PMID- 15442698
TI  - [Case of extrauterine pregnancy at term with dead fetus].

PMID- 15442699
TI  - [Organized treatment of trachoma].

PMID- 15442700
TI  - [History of local anesthesia in Russian surgery].

PMID- 15442701
TI  - [Problems of medical schools].

PMID- 15442702
TI  - [The medical institute plan for better medical services in the community].

PMID- 15442703
TI  - [Practical aspects of the cooperation of physicians of the Kazan Institute with
      public health].

PMID- 15442704
TI  - [The aspects of public health in the Soviet Union].

PMID- 15442705
TI  - [Certain problems of reorganization of public health in cities].

PMID- 15442706
TI  - [Certain problems of organization of specialized services for the rural
      population].

PMID- 15442707
TI  - [Reorganization of public health system in the Budennov district].

PMID- 15442708
TI  - [Hygiene in the Soviet Union].

PMID- 15442709
TI  - [State of hygiene and sanitation education in the Soviet Union].

PMID- 15442710
TI  - [Strive for cleanliness and culture in industry].

PMID- 15442711
TI  - [Superiority of medical sciences in the Soviet Union].

PMID- 15442712
TI  - [PROFESSOR F G Mukhamed'iarov].

PMID- 15442713
TI  - Researches on the radiotherapy of oral cancer.

PMID- 15442714
TI  - [Mikulicz's drainage in acute diffuse appendicular peritonitis in children].

PMID- 15442715
TI  - [Clinical studies of congenital renal hypoplasia].

PMID- 15442716
TI  - [Liver diseases].

PMID- 15442717
TI  - [Effects of methylthiouracil and aminothiazole in preoperative therapy in
      Basedow's disease and thyreotoxicosis].

PMID- 15442718
TI  - [Vitamins in ophthalmology].

PMID- 15442719
TI  - [Congenital cardiac abnormalities and possibilities of their surgical therapy].

PMID- 15442720
TI  - [Anuria in children].

PMID- 15442721
TI  - [Chronic eczema cured by appendectomy].

PMID- 15442722
TI  - [Case of spontaneous rupture of the spleen].

PMID- 15442723
TI  - [Results of treatment of tuberculosis with streptomycin].

PMID- 15442724
TI  - [Treatment of varicose veins and their complications].

PMID- 15442725
TI  - [Relapses and aggravation in tuberculous meningitis treated with streptomycin].

PMID- 15442726
TI  - [Effect of dihydroergotamine on the mechanism of contraction of the uterus and
      dilatation of the cervicoisthmian canal in labor].

PMID- 15442727
TI  - [Implantation of the choledochus and pancreas into the jejunum in cancer of the
      head of the pancreas].

PMID- 15442728
TI  - [Post-vaccinal encephalitis and its prevention].

PMID- 15442729
TI  - [New surgical technics in gynecology].

PMID- 15442730
TI  - [Short revue of retinitis albuminurica gravidarum and retinitis eclamptica].

PMID- 15442731
TI  - [Treatment of sciatica with high frequency waves].

PMID- 15442732
TI  - [Not Available].

PMID- 15442733
TI  - [Old and new methods in diagnosis and treatment of Addison's disease].

PMID- 15442734
TI  - [Relapse of Basedow's disease, with grave symptoms of cardiac insufficiency,
      following subtotal thyroidectomy, cured by methylthiouracil].

PMID- 15442735
TI  - [Case of toxic effect of overdosage of vitamin B].

PMID- 15442736
TI  - [Malignant course of erythema nodosum].

PMID- 15442737
TI  - [Case of pleuropulmonary actinomycosis treated with penicillin].

PMID- 15442738
TI  - [Hand-Schuller-Christian syndrome in a 26 month old child].

PMID- 15442739
TI  - [Dental caries in parodentosis].

PMID- 15442740
TI  - [Prevention of dental caries with sulfanalgezin].

PMID- 15442741
TI  - [Prevention of dental caries by means of fluorization of teeth].

PMID- 15442742
TI  - [Glycolytic power of mixed saliva in subjects, resistant and disposed to dental
      caries].

PMID- 15442743
TI  - [pH and chlorides in saliva in dental caries].

PMID- 15442744
TI  - [Anaerobic bacteria of the Perfrigens group in normal and pathologic conditions
      of the oral cavity].

PMID- 15442745
TI  - [Effect of antiulcerin; oil extract of cotton weed, in stomatitis].

PMID- 15442747
TI  - [Combined therapy of lupus vulgaris of the oral mucosa].

PMID- 15442746
TI  - [Treatment of acute forms of ulcerative stomatitis with penicillin].

PMID- 15442748
TI  - [Morphologic structure modifications of the temporomaxillary joint due to
      growth].

PMID- 15442749
TI  - [Innervation of the capsule of the lower jaw].

PMID- 15442750
TI  - [Cancer and osteonecrosis of the lower jaw following irradiation].

PMID- 15442751
TI  - [Experimental clinical studies on the effect of aqueous and alcohol solutions of
      diocain, used in local application].

PMID- 15442752
TI  - [Local application method in anesthesia].

PMID- 15442753
TI  - [Incomplete extraction of teeth].

PMID- 15442754
TI  - [Method of correction of palatal position of the frontal teeth].

PMID- 15442755
TI  - [Growth and development of dental arch].

PMID- 15442756
TI  - [Dental crowns of plastic material AKR 7-10].

PMID- 15442757
TI  - [Gnathodynamometric effect of physiologic thresholds of dental sensitivity ot
      masticatory pressure].

PMID- 15442758
TI  - [Pivot teeth of plastic material protected by a metallic plate].

PMID- 15442759
TI  - [Wire lip refractor].

PMID- 15442760
TI  - [The quality of work in odontology].

PMID- 15442761
TI  - [Relation between reticulosarcoma and leukemia; theory of the neoplastic nature
      of leukemia].

PMID- 15442762
TI  - [Small-field irradiation of bronchial carcinoma].

PMID- 15442763
TI  - [Clinical aspects and radiotherapy of osteosarcoma].

PMID- 15442764
TI  - [Ultrafractionation; experimental studies on the biologic effect of intermittent
      roentgen irradiation].

PMID- 15442765
TI  - [Critical observations on roentgenotherapy of peptic ulcer].

PMID- 15442766
TI  - [Sudeck's syndrome and roentgenotherapy].

PMID- 15442767
TI  - [Radium applicator with ball-and-socket joint for vaginal use].

PMID- 15442768
TI  - [Ring and cap diaphragms for contact irradiation with Chaoul's tube].

PMID- 15442769
TI  - [Azulol, a new synthetic remedy for cutaneous reactions to radiation].

PMID- 15442770
TI  - [The problem of membrane permeability; the field].

PMID- 15442771
TI  - [Changes of the structural elements of the blood following roentgen irradiation].

PMID- 15442772
TI  - [Therapeutic effects of ultrasonic waves].

PMID- 15442773
TI  - [Interpretation of the therapeutic mode of action of ultrasonic wares based upon
      their effect on tissue respiration].

PMID- 15442774
TI  - [Dependence of biologic ultrasonic reactions upon particle amplitude as an
      interpretation of their therapeutic mode of action].

PMID- 15442775
TI  - [Focusing ultrasonic vibrators for therapeutic purposes].

PMID- 15442776
TI  - [Roentgenotherapy of nocturnal enuresis].

PMID- 15442777
TI  - [Lethal effect of radiant energy upon drosophila eggs as a problem in
      biophysics].

PMID- 15442778
TI  - [Brief report on the incidence of dental caries in Finnish schools during the
      autumn of 1946].

PMID- 15442779
TI  - [Comparative studies on the etiology of fractures of the jaw].

PMID- 15442780
TI  - [Use and effect of fluorides in prophylaxis of dental caries].

PMID- 15442781
TI  - [Fifty-seventh annual report of the Finnish Dental Society].

PMID- 15442782
TI  - [The distribution of dentists in Finland in the light of labor statistics].

PMID- 15442783
TI  - Resistance of explanted gastric mucosa to various chemical and physical agents.

PMID- 15442784
TI  - The extent to which one may interfere with the blood supply of the esophagus and
      obtain healing on antastomosis.

PMID- 15442785
TI  - Studies on an antithrombin. III. A plasma antithrombin test for the prediction of
      intravascular clotting.

PMID- 15442786
TI  - An experimental study of regional heparinization.

PMID- 15442787
TI  - Saphenous neurectomy in the treatment of selected cases of painful ulceration of
      the leg.

PMID- 15442788
TI  - Perianal extramammary Paget's disease; report of a case.

PMID- 15442789
TI  - Rupture of the bowel in the newborn infant, including a case report of rupture in
      the large intestine with recovery.

PMID- 15442790
TI  - The cure of hypertension by nephrectomy; a ten-year follow-up of a case.

PMID- 15442791
TI  - Wringer injury.

PMID- 15442792
TI  - The eosinophil response to surgical trauma.

PMID- 15442793
TI  - Immediate and late results of the surgical therapy of acute perforated gastric
      and duodenal ulcer.

PMID- 15442794
TI  - Acute intestinal obstruction; comparative studies of small intestinal and colic
      obstruction.

PMID- 15442795
TI  - Obstructive jaundice as a complication of duodenal ulcer; a case report.

PMID- 15442796
TI  - Acute jejunogastric intussusception; report of a case report.

PMID- 15442797
TI  - The genesis of gastroduodenal ulcer following burns; an experimental study.

PMID- 15442798
TI  - Resident training and specialization in surgery.

PMID- 15442799
TI  - Quantitative aspects of hemorrhage.

PMID- 15442800
TI  - Retardation of wound healing by cortisone.

PMID- 15442801
TI  - Sodium deficiency in surgical patients and the failure of urine chloride as a
      guide to parenteral therapy.

PMID- 15442802
TI  - Experimental tuberculosis; effects of anastomosis between systemic and pulmonary
      arteries on tuberculosis in monkeys.

PMID- 15442803
TI  - Cardiotomy into an empty left ventricle.

PMID- 15442804
TI  - Observations on experimental atriovenous anastomoses, with particular reference
      to congenital anomalies of the venous return to the heart, and to cyanosis.

PMID- 15442805
TI  - Thoracic aortic coarctation; its experimental production in dogs, with special
      reference to technical methods capable of inducing significant intraluminal
      stenosis.

PMID- 15442806
TI  - A functional study of afferent fibers in peripheral sympathetic nerves.

PMID- 15442807
TI  - Some physiologic effects of lumbodorsal sympathectomy for hypertension.

PMID- 15442808
TI  - Venous adaptation following bilateral radical neck dissection with excision of
      the jugular veins.

PMID- 15442809
TI  - An improved method of venography for the preoperative evaluation of the
      postphlebitic extremity.

PMID- 15442810
TI  - The surgical treatment of intracranial angiomatous malformations.

PMID- 15442811
TI  - Complications following subtotal gastric resections performed since June, 1944,
      for peptic ulcer in 132 patients.

PMID- 15442812
TI  - Aids in the management of ileostomies; a new plastic bag.

PMID- 15442813
TI  - A new surgical treatment for Hirschsprung's disease.

PMID- 15442814
TI  - The principle of complete exclusion in fistulas of the small intestine.

PMID- 15442815
TI  - Sickle-cell anemia: a surgical problem; further observation on the surgical
      implications of sickle-cell anemia.

PMID- 15442816
TI  - Neck dissections in cancer of the lower lip; five-year results in 179 patients.

PMID- 15442817
TI  - Permanent camouflage of corneal scars using insoluble tattoo pigments.

PMID- 15442818
TI  - Pheochromocytoma; the use of adrenergic blocking agents in the operative
      management.

PMID- 15442819
TI  - Anastomosis of the cervical esophagus: experimental evaluation of peritoneal
      grafts; two-layer anastomosis.

PMID- 15442820
TI  - Surgical aspects of abnormal twinning.

PMID- 15442821
TI  - Contractility of the human uterus recorded by new methods.

PMID- 15442822
TI  - Intertrochanteric fractures of the femur; an analysis of the end results of 126
      fractures treated by various methods.

PMID- 15442823
TI  - Experience with the operative management of 280 strictures of the bile ducts,
      with a description of a new method and a complete follow-up study of the end
      results in 229 of the cases.

PMID- 15442824
TI  - Vaginal hysterectomy.

PMID- 15442825
TI  - Localized paralytic ileus; an early roentgen sign in acute pancreatitis.

PMID- 15442826
TI  - Surgical complications of congenital anomalies of the umbilical region.

PMID- 15442827
TI  - Pneumothorax and mediastinal emphysema complicating neck surgery.

PMID- 15442828
TI  - Cystic hemangioblastomas of the cerebellum; end results in 25 verified cases.

PMID- 15442829
TI  - An evaluation of pH-isoderm G-11 and a liquid soap containing G-11 when used as
      the preoperative scrub.

PMID- 15442830
TI  - Nonpenetrating abdominal injury.

PMID- 15442831
TI  - Presidential gunshot wounds; 3 cases reports.

PMID- 15442832
TI  - Multiple balloon kymograph recording of the comparative action of morphine and
      placebos on the motility of the upper small intestine in man.

PMID- 15442833
TI  - Experimental maintenance of life by a mechanical heart and lung during occlusion
      of the venae cavae followed by survival.

PMID- 15442834
TI  - Whole thickness skin grafts in the treatment of hernias; analysis of 211 cases.

PMID- 15442835
TI  - Intussusception in infancy and childhood.

PMID- 15442836
TI  - Intraepithelial carcinoma of the cervix.

PMID- 15442837
TI  - Hysterography and hysterosalpingography; an analysis of 2,500 cases with special
      emphasis on technique and safety of the procedure.

PMID- 15442838
TI  - Internal derangement of the talofibular component of the ankle.

PMID- 15442839
TI  - Shoulder girdle amputation.

PMID- 15442840
TI  - Factors influencing the prevention and cure of cancer of the thyroid.

PMID- 15442841
TI  - The results of surgical treatment of cancer of the breast throughout a period of
      forty years.

PMID- 15442842
TI  - Benign mesotheliomas (adenomatoid tumors) of the genital tract.

PMID- 15442843
TI  - Carcinoma of the buccal mucosa: treatment and end results.

PMID- 15442844
TI  - The vagus nerve in cardiac arrest; the effect of hypercapnia, hypoxia and
      asphyxia on reflex inhibition of the heart.

PMID- 15442845
TI  - Absorption rates, electrolyte and volume changes following subcutaneous and
      intraperitoneal injections of solutions containing salt, glucose, and amino
      acids.

PMID- 15442846
TI  - Studies in acute cholecystitis. III. the pathological process in relation to the
      clinical management of the disease; the fallacy of the "critical period".

PMID- 15442847
TI  - Preliminary report on the use of bone bank bone.

PMID- 15442848
TI  - The selective management of megacolon in infants and children.

PMID- 15442849
TI  - A new concept of venous thrombosis.

PMID- 15442851
TI  - Surgical management of duodenal ulcer.

PMID- 15442850
TI  - An experimental study of healing in the common bile duct.

PMID- 15442852
TI  - The use of plasma volume determination as a guide to saline administration in
      surgical patients.

PMID- 15442853
TI  - Cancer of the rectum; five and ten year follow-up study of cases of cancer below
      the peritoneal reflection.

PMID- 15442854
TI  - Blood volume and blood biochemical studies in patients undergoing radical
      surgery.

PMID- 15442855
TI  - Modern treatment of chronic osteomyelitis with topical detergent antibiotic
      therapy.

PMID- 15442856
TI  - Regional enteritis; clinical and experimental observations.

PMID- 15442857
TI  - Nylon arthroplasty of the knee joint in chronic arthritis.

PMID- 15442858
TI  - Partial nephrectomy versus pyelolithotomy and nephrolithotomy in the treatment of
      localized calculous disease of the kidney, with a report of 17 partial
      nephrectomies.

PMID- 15442860
TI  - Surgical lesions of the pancreas.

PMID- 15442859
TI  - Traumatic diaphragmatic hernia.

PMID- 15442861
TI  - Strictures of the common and hepatic bile ducts and their treatment.

PMID- 15442862
TI  - Anatomic relationship of the cystic duct to the cystic artery in 100 consecutive
      cases of cholecystectomy.

PMID- 15442863
TI  - The surgical management of the complications of diverticulitis of the large
      intestine; analysis of 202 cases.

PMID- 15442864
TI  - The treatment of familial polyposis of the colon.

PMID- 15442865
TI  - Surgical treatment of carcinoma of the right portion of the colon.

PMID- 15442866
TI  - The influence of sympathectomy on the gastro-intestinal tract.

PMID- 15442867
TI  - Peritoneoscopy: an evaluation of 396 examinations.

PMID- 15442868
TI  - Mesenteric vascular occlusion.

PMID- 15442869
TI  - Primary omental cysts of clinical importance.

PMID- 15442870
TI  - Chylous cysts of the abdomen.

PMID- 15442871
TI  - Bezoars of the stomach.

PMID- 15442873
TI  - Nasal deformities involving the bony and cartilaginous framework.

PMID- 15442872
TI  - Remarks concerning diagnostic and therapeutic blocks for some types of abdominal
      pain.

PMID- 15442874
TI  - Epithelioma of the lower lip.

PMID- 15442875
TI  - Giant hemolymph node; report of two cases.

PMID- 15442876
TI  - Perforation of the esophagus; an analysis of 50 cases and an account of
      experimental studies.

PMID- 15442877
TI  - Primary fibrosarcoma of the lung; report of 2 cases.

PMID- 15442878
TI  - Effect of arteriovenous fistula on growth of bone; an experimental study.

PMID- 15442879
TI  - Benign giant-cell tumors; a report of 7 cases in which the bones of the hands and
      feet were involved.

PMID- 15442880
TI  - Wertheim hysterectomy.

PMID- 15442881
TI  - Vesical and enterovesical fistulas.

PMID- 15442882
TI  - [Quantitative determination of nikethamide according to the eleventh edition of
      the Swedish Pharmacopeia].

PMID- 15442883
TI  - [Observations on the operation of the pharmacy].

PMID- 15442884
TI  - [Observations on the operation of the pharmacy].

PMID- 15442885
TI  - [Balanced occlusion with special reference to construction of the full
      prosthesis].

PMID- 15442886
TI  - [Use of penicillin in pulp therapy; a review of the literature].

PMID- 15442887
TI  - [Recording the condyle path by means of the protrusion index; a study with the
      articulator].

PMID- 15442888
TI  - [Practical and clinical aspects of dental porcelain].

PMID- 15442889
TI  - [Practical and clinical aspects of acrylics].

PMID- 15442890
TI  - [Porcelain facings without anchorage in the root canal].

PMID- 15442891
TI  - [New, simple amalgam vibrator].

PMID- 15442893
TI  - The fractionation of proteins by electrophoresis-convection.

PMID- 15442892
TI  - Hydrolysis of proteins.

PMID- 15442894
TI  - Studies on polypeptides and amino acids by countercurrent distribution.

PMID- 15442895
TI  - Studies on the cytochemistry of proteins.

PMID- 15442896
TI  - Competitive reactions and antagonisms in the biosynthesis of amino acids by
      neurospora.

PMID- 15442897
TI  - The quantitative analysis of amino acids in proteins: insulin and lysozyme.

PMID- 15442898
TI  - The metabolism of peptides.

PMID- 15442899
TI  - X-ray analysis and protein structure.

PMID- 15442900
TI  - Protein mercaptides.

PMID- 15442901
TI  - Localization of cellular proteins by enzymatic hydrolysis.

PMID- 15442902
TI  - The application of the isotopic derivative method to the analysis of proteins.

PMID- 15442903
TI  - The nature of some ion-protein complexes.

PMID- 15442904
TI  - The application of the isotopic derivative technic to the study of protein
      structure.

PMID- 15442906
TI  - The liver proteins.

PMID- 15442905
TI  - Structure and enzymatic break-down of proteins.

PMID- 15442907
TI  - Size relationship among similar proteins; association and dissociation reactions
      of protein units.

PMID- 15442908
TI  - Some chemical investigations on the structure of insulin.

PMID- 15442909
TI  - Some aspects of the biosynthesis of amino acids.

PMID- 15442910
TI  - Some consideration of the interaction of the metal peptidases with their
      substrates.

PMID- 15442911
TI  - Chromatographic determination of the amino acid composition of proteins.

PMID- 15442912
TI  - Physical and chemical studies of gramicidin and some implications for the study
      of proteins.

PMID- 15442913
TI  - Peptide bond synthesis in normal and malignant tissue.

PMID- 15442914
TI  - [75th anniversary of V. P. Filatov].

PMID- 15442915
TI  - [Experimental data on the mechanism of Filatov's method of tissue therapy].

PMID- 15442916
TI  - [Biologic properties of placental extract].

PMID- 15442917
TI  - [Experiences with Filatov's method of tissue therapy].

PMID- 15442918
TI  - [Results of cod liver oil injections therapy (Filatov's method)].

PMID- 15442919
TI  - [Effect of application of extract of the placenta on the intraoccular pressure
      (Filatov's method)].

PMID- 15442920
TI  - [Plastic repair of the exterior part of the upper eyelid with a part of the lower
      eyelid].

PMID- 15442922
TI  - [Case of spontaneous and traumatic pulsating exophthalmus].

PMID- 15442921
TI  - [Modern principles in the surgery of the lacrimal sac].

PMID- 15442923
TI  - [Gabor DITROI, 1884-1950].

PMID- 15442924
TI  - [Contribution to the knowledge of ocular blood circulation].

PMID- 15442925
TI  - [Essential hypertension].

PMID- 15442926
TI  - [Circulatory disorders of the retina].

PMID- 15442927
TI  - [Retinal periphlebitis].

PMID- 15442928
TI  - [Sudden blindness following gastric hemorrhage].

PMID- 15442929
TI  - [Operation for cataract in grave myopia].

PMID- 15442930
TI  - [Physiotherapy in ocular diseases].

PMID- 15442931
TI  - [Clinical aspect of the eye fundus and its significance in tuberculous meningitis
      in early childhood and in miliary tuberculosis treated by streptomycin].

PMID- 15442932
TI  - [Experimental treatment of ocular trauma caused by chemical agents with Priscol].

PMID- 15442933
TI  - [Case of opticochiasmal arachnoiditis cured by conservative therapy].

PMID- 15442934
TI  - [Possibilities of tissue therapy; preliminary report].

PMID- 15442935
TI  - [American orthodontics today].

PMID- 15442937
TI  - [Movable interdental clasp].

PMID- 15442936
TI  - [Forensic odontology; case report; bite marks].

PMID- 15442938
TI  - [Perspectives on hospital organization].

PMID- 15442939
TI  - [Center for rehabilitation and re-education].

PMID- 15442940
TI  - [Financial statistics].

PMID- 15442941
TI  - [Realization of a mobile sanitary unit destined for Nigeria].

PMID- 15442942
TI  - [Comment on the so called teaching on the human constitution].

PMID- 15442943
TI  - [Postwar rheumatism].

PMID- 15442944
TI  - [Sympathectomy in treatment of cerebral syndromes of high blood pressure].

PMID- 15442945
TI  - [Evaluation of surgical methods in treatment of high blood pressure].

PMID- 15442946
TI  - [Effect of the section of abdominal nerves and removal of the first and second
      lumbar sympathetic ganglions on the renal function in high blood pressure].

PMID- 15442947
TI  - [Clinical importance of the electrocardiogram in high blood pressure; changes of
      the ventricular complex in thoracic leads CR1 and CR6].

PMID- 15442948
TI  - [Axonometry in the diagnosis of cardiac diseases].

PMID- 15442949
TI  - [Stability of the level of venous pressure; phlebotonographic observations].

PMID- 15442950
TI  - [Lead poisoning with manifestations of cardio-vascular disorders of toxic
      origin].

PMID- 15442951
TI  - [Liver modifications in nephritis].

PMID- 15442952
TI  - [Bone marrow transplantation].

PMID- 15442953
TI  - [Water metabolism in normal state and in anemia following blood transfusion].

PMID- 15442954
TI  - [Normal myelogram].

PMID- 15442955
TI  - [Quantitative modification of gastric juice and of the acidity by the reflex of
      the large intestine in man].

PMID- 15442956
TI  - [Study of characteristics of the reaction of connective tissue in Head's zones in
      peptic ulcers].

PMID- 15442957
TI  - [C-hypovitaminosis in chronic dysentery and its pathogenetic importance].

PMID- 15442958
TI  - [Mineral content of blood plasma in acute rheumatism].

PMID- 15442959
TI  - [New pharmaceutic preparations from native plants in treatment of internal
      diseases].

PMID- 15442960
TI  - [Pavlov's theory and internal medicine].

PMID- 15442961
TI  - [Role of therapeutic diet in contemporary medicine].

PMID- 15442962
TI  - [Remote sequels of epidemic hepatitis (Botkin's disease)].

PMID- 15442963
TI  - [Clinical importance of cold agglutinins].

PMID- 15442964
TI  - [Division of the clinical course of hypertension into stages of phases].

PMID- 15442965
TI  - [Stomach in certain diseases of the gallbladder and liver].

PMID- 15442966
TI  - [Typical reactions of the bone marrow in diseases of the kidney; disturbance
      mechanism of medullary hemopoiesis].

PMID- 15442967
TI  - [Determination of proteins, albumin, globulin and diagnostic determination of
      fibrinogen in the blood based upon the ring formation in overlaying of serum on
      nitric acid].

PMID- 15442968
TI  - [Pericardiac diverticula].

PMID- 15442969
TI  - [Pathogenesis of bradycardia and hypotonia in relapsing fever].

PMID- 15442970
TI  - [Contemporary orientations of Soviet medicine].

PMID- 15442971
TI  - [Testosterone therapy of leukorrhea].

PMID- 15442972
TI  - [Progress in urology].

PMID- 15442973
TI  - [New chemical methods in liver function tests].

PMID- 15442974
TI  - [Treatment of hypertension and heart and kidney disease with rice diet].

PMID- 15442975
TI  - [Progress in urology; value of cytologic examinations in diagnosis of tumors of
      the urinary organs; value of modern antibiotics in treatment of urinary
      infections].

PMID- 15442976
TI  - [Therapeutic percutaneous administration of unsaturated fatty acids].

PMID- 15442977
TI  - [New applications of heparin therapy].

PMID- 15442978
TI  - [Indications and results of exchange transfusion].

PMID- 15442979
TI  - [Clinical study of the therapeutic properties of extract of Raphanus].

PMID- 15442980
TI  - [Spasmolytic action and local anesthetic action; comparison in a series of
      papaverine derivatives].

PMID- 15442981
TI  - [The common and particular properties of folic acid and cobamine (vitamin B12)].

PMID- 15442982
TI  - [Synergistic action of folic acid and cobamine (vitamin B12) in the pseudo
      irreversible phase of pernicious anemia].

PMID- 15442983
TI  - [Practical treatment of the so-called essential anemias based on
      erythrocytometry].

PMID- 15442984
TI  - [Action of the male hormone on retarded growth in boys].

PMID- 15442985
TI  - [Treatment of retarded growth in boys by synthetic estrogens; 4 cases].

PMID- 15442986
TI  - [Protein calcium of the blood and its variations; therapeutic deductions].

PMID- 15442987
TI  - [The hyaluronic acid-hyaluronidase system; clinical use of hyaluronidase in
      infusions].

PMID- 15442988
TI  - [Clinical experience with dehydasal].

PMID- 15442989
TI  - [Paravenous irritation of substances used in sclerosing varicose veins].

PMID- 15442990
TI  - [Conservative therapy of disorders of the peripheral circulation].

PMID- 15442991
TI  - [A new method in conservative therapy of endangiitis obliterans].

PMID- 15442992
TI  - [Development of tuberculous pericarditis following roentgen irradiation of a
      costal abscess].

PMID- 15442993
TI  - [Physician and pharmacist].

PMID- 15442994
TI  - [Abuses in medicine].

PMID- 15442995
TI  - [Virus diseases of the respiratory tract].

PMID- 15442996
TI  - [Experimental study of combined sulfonamide and penicillin therapy of necrotic
      jejunitis].

PMID- 15442997
TI  - [A new jejunal probe].

PMID- 15442998
TI  - [Conservative therapy of pulmonary abscess].

PMID- 15442999
TI  - [Physicians and the chemistry of sugar].

PMID- 15443000
TI  - [Social medicine].

PMID- 15443002
TI  - [Chloromycetin therapy of typhoid fever].

PMID- 15443001
TI  - [Importance of auricular flutter in the etiologic diagnosis of heart disease].

PMID- 15443003
TI  - [Cancer of the nose and paranasal sinuses].

PMID- 15443004
TI  - [Malnutrition in breast-fed children].

PMID- 15443005
TI  - [Workers protection law and subordinate staff physicians].

PMID- 15443006
TI  - [Mycotic infection of the respiratory tract].

PMID- 15443007
TI  - [Mediastinal emphysema and bilateral pneumothorax as a complication following
      tracheotomy for pseudocroup].

PMID- 15443008
TI  - [Flying ambulances in northern Norway; a report on 33 flights].

PMID- 15443009
TI  - [Isolated subcutaneous lesion of the pancreas, combined with atypical pseudocysts
      of the pancreas].

PMID- 15443010
TI  - [Not Available].

PMID- 15443011
TI  - [The new curriculum].

PMID- 15443013
TI  - [Epilepsy for the general practitioner].

PMID- 15443012
TI  - [The public medical officer's office and residence; medical districts without
      medical officers].

PMID- 15443014
TI  - [Juvenile delinquency factors in the Toulouse district].

PMID- 15443015
TI  - [Puerperal psychoneuroses; treatment and prognosis].

PMID- 15443016
TI  - [Out-patient service in the treatment of mental diseases].

PMID- 15443017
TI  - [Extended Peet and Smithwick thoraco-lumbar sympathectomies in treatment of
      arterial hypertension; technic and statistics on 75 cases].

PMID- 15443018
TI  - [Corneal reflex affected by a temporal meningioma].

PMID- 15443019
TI  - [Neurotic reactions following skull injuries].

PMID- 15443020
TI  - [Modern method of classification of epilepsy].

PMID- 15443021
TI  - [Myocardiac contusions caused by nonpenetrating injuries].

PMID- 15443022
TI  - [Examination of blood types in determination of paternity].

PMID- 15443023
TI  - [Kernicterus].

PMID- 15443024
TI  - [Two years of psychiatric survey of the prisoners of Saint Michel].

PMID- 15443025
TI  - Primary chorioretinal aberrations with night blindness; classification.

PMID- 15443026
TI  - Symptoms, signs and differential diagnosis.

PMID- 15443027
TI  - Primary chorioretinal aberrations with night blindness; genetics.

PMID- 15443028
TI  - Primary chorioretinal aberrations with night blindness; pathology.

PMID- 15443029
TI  - Primary chorioretinal aberrations with night blindness; treatment and
      conclusions.

PMID- 15443030
TI  - Primary chorioretinal aberrations with night blindness; discussion.

PMID- 15443031
TI  - Nuclear deafness and the nerve deaf child: the importance of the Rh factor.

PMID- 15443032
TI  - The use of speech tests for the evaluation of clinical procedures.

PMID- 15443033
TI  - The clinical application of bone conduction audiometry.

PMID- 15443034
TI  - Physiology and pathology of sound conduction in the ear.

PMID- 15443035
TI  - Conservation of hearing function.

PMID- 15443036
TI  - Industrial ophthalmology.

PMID- 15443037
TI  - Use of sulfhydryl in the treatment of corneal scars following chemical eye burns
      and ulcers.

PMID- 15443038
TI  - FIFTY-FIFTH annual meeting of the American Academy of Ophthalmology and
      Otolaryngology. October 8 to 13, 1950, Chicago.

PMID- 15443039
TI  - The problem of loiasis in West Africa with special reference to recent
      investigations at Kumba in the British Cameroons and at Sapele in Southern
      Nigeria.

PMID- 15443040
TI  - Hetrazan in the treatment of filariasis due to Wuchereria malayi.

PMID- 15443041
TI  - The treatment of urinary bilharzia in Egypt by miracil D.

PMID- 15443042
TI  - A study of sleeping sickness in an endemic area of the Belgian Congo over a
      period of ten years.

PMID- 15443043
TI  - Hereditary transmission of Theileria annulata infection in the tick, Hyalomma
      aegyptium neum.

PMID- 15443044
TI  - Studies on protozoa. Part II: The golden hamster (Cricetus auratus) and cotton
      rat (Sigmodon hispidus) as experimental hosts for Leishmania donovani.

PMID- 15443045
TI  - Report of two additional cases and an analysis of the pathogenesis of ainhum on
      the Isthmus of Panama.

PMID- 15443046
TI  - Tropical thromboangiitis of the splenic vessels and its relationship to primary
      splenic abscess.

PMID- 15443047
TI  - Trivalent sodium antimony gluconate in the treatment of Schistosomiasis.

PMID- 15443048
TI  - James Ormiston McWilliam (1807-1862).

PMID- 15443049
TI  - Notes on medical rehabilitation in Canada.

PMID- 15443050
TI  - The rehabilitation needs of the disabled in Canada.

PMID- 15443051
TI  - Special placement of handicapped persons.

PMID- 15443052
TI  - Review of fundamental principles of chemotherapeutic and antibiotic therapy.

PMID- 15443053
TI  - Analysis of departmental morbidity statistics.

PMID- 15443054
TI  - The present status of orbital implants.

PMID- 15443055
TI  - Pulmonary calcification and histoplasmin sensitivity.

PMID- 15443056
TI  - Preliminary reports on prefrontal lobotomy; the psychological aspects.

PMID- 15443058
TI  - Tuberculosis in Holland.

PMID- 15443057
TI  - Report on Winnipeg flood situation.

PMID- 15443059
TI  - The treatment of tuberculous meningitis.

PMID- 15443060
TI  - STREPTOMYCIN in the treatment of tuberculous meningitis.

PMID- 15443061
TI  - [Internal secretion and tuberculosis].

PMID- 15443062
TI  - [Method of local treatment of tuberculous caverns of the lung].

PMID- 15443063
TI  - [Late dangers of intracavitary chemotherapeutic puncture].

PMID- 15443064
TI  - [Treatment of pleural effusion in pulmonary tuberculosis].

PMID- 15443065
TI  - [Contraindications for stomach surgery in pulmonary tuberculosis].

PMID- 15443066
TI  - [Comparative investigation of various tuberculin patch tests].

PMID- 15443067
TI  - [Cutaneous tuberculin tests; case reports].

PMID- 15443068
TI  - [Pulmonary tuberculosis in the concentration camp at Theresienstadt, compared
      with its incidence in other German concentration camps].

PMID- 15443069
TI  - [Microscopic structure of the nucleus in tumor cells].

PMID- 15443070
TI  - [Action of nitrogen mustard on the action in vitro of acid and alkaline
      phosphatase in human serum].

PMID- 15443071
TI  - [Mixed tumors of the head and neck, with special reference to their extraparotid
      localization].

PMID- 15443072
TI  - [The myocardium in tumor patients with vegetative or verrucous endocarditis].

PMID- 15443073
TI  - [Examination of the nasal secretions of heroin addicts for morphine and its
      derivatives].

PMID- 15443074
TI  - [A rare anomaly and volvulus of the large intestine].

PMID- 15443076
TI  - [An intervertebral disk hernia near the conus terminalis].

PMID- 15443075
TI  - [Treatment of pneumonia with a single daily muscular injection of crystallin
      penicillin].

PMID- 15443078
TI  - [The treatment of acute renal failure by peritoneal irrigation].

PMID- 15443077
TI  - [A case of Hodgkin's disease with primary ileo-jejunal localization].

PMID- 15443079
TI  - [A rare hypophyseal tumor (cranio-pharyngioma) treated by surgery].

PMID- 15443080
TI  - [The effects of pituitrin on the bone marrow and on lymphosarcoma].

PMID- 15443081
TI  - [The adaptation syndrome].

PMID- 15443082
TI  - [Perforation of a tuberculous ileum].

PMID- 15443083
TI  - [Chloromycetin in typhoid fever therapy].

PMID- 15443084
TI  - [Jacksonian epilepsy as sequel of a post-traumatic fibrinous cicatrix: operative
      treatment].

PMID- 15443085
TI  - [Lymphosarcoma of the small intestine].

PMID- 15443086
TI  - [Heart catheterization].

PMID- 15443087
TI  - [Combined intramuscular and intrameningeal streptomycin therapy of tuberculous
      meningitis, with special reference to its toxic effect upon the eighth cranial
      nerve].

PMID- 15443088
TI  - [Determination of toxicity of streptomycin preparations].

PMID- 15443089
TI  - [Streptomycin therapy of acute tuberculous otitis media].

PMID- 15443090
TI  - [Frequency of complications in sulfadimethylpyrimidine (elkosin) therapy in 443
      cases].

PMID- 15443091
TI  - [Use of thiouracil derivatives in pregnancy].

PMID- 15443092
TI  - [Localized myxedema in Basedow's disease].

PMID- 15443093
TI  - [Severe iodism complicated by cerebral edema].

PMID- 15443094
TI  - [Experimental and clinical experience with a new antihistamine].

PMID- 15443095
TI  - [Thyrotoxicosis in a nine year old boy].

PMID- 15443096
TI  - [Case of hematuria and anuria following sulfamerazin therapy].

PMID- 15443097
TI  - [Use of central analeptics in acute hypnotic poisoning].

PMID- 15443098
TI  - [Observations on treatment of acute hypnotic poisoning].

PMID- 15443099
TI  - [Ulcerocarcinoma of the stomach and surgical indications].

PMID- 15443100
TI  - [Gastric sarcoma].

PMID- 15443102
TI  - [Heredity of peptic ulcer].

PMID- 15443101
TI  - [Relation between cancer and gastric ulcer, illustrated with case studies of
      cancer and follow-up studies of gastric ulcer cases].

PMID- 15443103
TI  - [Perforated peptic ulcer of the jejunum].

PMID- 15443104
TI  - [Diverticula of the esophagus].

PMID- 15443105
TI  - [Method of preserving partial stomach function following extensive
      esophagogastrectomy].

PMID- 15443106
TI  - [Medical and modern surgical therapy of ulcerative colitis].

PMID- 15443107
TI  - [Medical and surgical therapy of ulcerating colitis].

PMID- 15443108
TI  - [Ulcerative colitis in pregnancy and labor].

PMID- 15443109
TI  - [3 unusual cases of obstructive jaundice due to neoplasms].

PMID- 15443110
TI  - [Pyloristenosis following consumption of diluted hydrochloric acid].

PMID- 15443111
TI  - [Risks for personnel engaged in roentgenography].

PMID- 15443112
TI  - [Medicine's economic declassification].

PMID- 15443113
TI  - [Treatment of paralysis agitans with some new preparations: parpanit, diparcol,
      and phenergan].

PMID- 15443114
TI  - [Treatment of parkinsonism with rigidyl (beta-diethylaminoethyl benzohydryl ether
      hydrochloride)].

PMID- 15443115
TI  - [Pharmacology of beta-diethylaminoethyl benzohydryl ether hydrochloride].

PMID- 15443116
TI  - [Not Available].

PMID- 15443117
TI  - [Aureomycin therapy of virus pneumonia].

PMID- 15443118
TI  - [Rheumatic pneumonia].

PMID- 15443119
TI  - [Arrangements for ophthalmological service at the hospital].

PMID- 15443120
TI  - [Legal induced abortion; a review of the indications, operations and primary
      complications of 566 cases in the years 1942-1948].

PMID- 15443121
TI  - [Deaths in early pregnancy].

PMID- 15443122
TI  - [Diamidine therapy of myelomatosis].

PMID- 15443123
TI  - [Polycythemia vera; course and prognosis].

PMID- 15443124
TI  - [Venereal disease in Denmark before, during and after the two world wars].

PMID- 15443125
TI  - [A comparison between cardiolipin and two other antigens in the Kahn test].

PMID- 15443126
TI  - [A new disease?].

PMID- 15443127
TI  - [History of psittacosis in the Faeroes].

PMID- 15443128
TI  - [Group therapy of alcoholism in the Ring i Ring, the Danish Alcoholics
      Anonymous].

PMID- 15443129
TI  - [Incidence of streptococcus infection in frail children].

PMID- 15443130
TI  - [Nosocomial streptococcus infections in a children's institution].

PMID- 15443131
TI  - [Latent and subclinical streptococcus infections].

PMID- 15443132
TI  - [Scabieslike eruption caused by Cheyletiella parasitivorax].

PMID- 15443133
TI  - [Two cases of polyarteritis modosa].

PMID- 15443134
TI  - [A cardboard prosthesis].

PMID- 15443135
TI  - [Physician's professional secrecy].

PMID- 15443136
TI  - [Retrobulbar neuritis and multiple sclerosis].

PMID- 15443137
TI  - [Problems of clinical radiobiology].

PMID- 15443138
TI  - [Fractures of the carpus, with special reference to fractures of the navicular
      bone].

PMID- 15443139
TI  - [Not Available].

PMID- 15443140
TI  - [Transabdominal and abdominotransanal resection of the rectum].

PMID- 15443141
TI  - [Millin's retropubic prostatectomy; results in a small, nonspecialized rural
      hospital].

PMID- 15443142
TI  - [Psychosomatic dermatology].

PMID- 15443143
TI  - [Tuberculosis in Denmark].

PMID- 15443145
TI  - [The new salary scales].

PMID- 15443144
TI  - [Social counselor's work in private treatment of alcoholism].

PMID- 15443146
TI  - [Effect of ACTH and cortisone on rheumatic fever].

PMID- 15443147
TI  - [Acrodynia; a review, and report of a case, with mercury in the urine, cured
      following treatment with dimercaptopropanol].

PMID- 15443148
TI  - [Significance of gonococci culture of rectal smear from women].

PMID- 15443149
TI  - [Frequency of benign paroxysmal disorders of the heart].

PMID- 15443150
TI  - [Chigger infestation (trombidiosis); an endemic caused by Leptus (Trombicula)
      autumnalis in the Thisted region].

PMID- 15443151
TI  - [Use of flexible materials (flexi-derm) for facial and digital prostheses].

PMID- 15443152
TI  - [Cardboard prosthesis].

PMID- 15443153
TI  - [Quincke's edema of tongue and larynx treated with antihistaminics].

PMID- 15443155
TI  - [A case of copra itch].

PMID- 15443154
TI  - [Opiophagy and morphinism].

PMID- 15443156
TI  - [Shock therapy of narcolepsy].

PMID- 15443157
TI  - [Three cases of epidemic meningitis with uveitis].

PMID- 15443158
TI  - [Ophthalmoplegic migraine with alternating ophthalmoplegia and exophthalmos].

PMID- 15443159
TI  - [Subarachnoid hemorrhage and acetanilid poisoning following radical ear surgery].

PMID- 15443160
TI  - [Diagnostic and therapeutic possibilities in lymphogranulomatosis benigna].

PMID- 15443161
TI  - [Dangers and mortality of gastric cancer in subjects with pernicious anemia].

PMID- 15443162
TI  - [Two cases of secondary intestinal tuberculosis treated with p-aminosalicylic
      acid].

PMID- 15443163
TI  - [American pediatrics].

PMID- 15443164
TI  - [Physical medicine and rehabilitation].

PMID- 15443165
TI  - [ACTH and cortisone and their clinical application in rheumatology].

PMID- 15443166
TI  - [Fibroblastic sarcoma of the great omentum].

PMID- 15443167
TI  - [From psychiatry to neurosurgery through neurology].

PMID- 15443168
TI  - [Congenital absence of the gallbladder].

PMID- 15443169
TI  - [Case of Lutembacher's disease].

PMID- 15443170
TI  - [Hygiene and social medicine].

PMID- 15443171
TI  - [Progress of hospital organization].

PMID- 15443172
TI  - [History of medicine in New France; alkermes and mineral kermes].

PMID- 15443173
TI  - [Three men--three theories--three errors?].

PMID- 15443174
TI  - [Variations on a Maurice Chevalier theme].

PMID- 15443175
TI  - [Diagnosis by elimination: mesothelioma, malignant tumor of the peritoneum].

PMID- 15443176
TI  - [Cerebral arteriographies, June 1-Dec. 31, 1949].

PMID- 15443177
TI  - [Ophthalmoplegia due to carotid aneurysm].

PMID- 15443178
TI  - [Treatment of zona by protamide].

PMID- 15443179
TI  - Perceptual factors in delayed response.

PMID- 15443180
TI  - Anatomical and surgical aspects in the operative management of varicocele.

PMID- 15443181
TI  - Meningeal metastasis from a carcinoma of the prostate; it's possible mechanism of
      production.

PMID- 15443182
TI  - Bilateral ureteral obstruction caused by metastatic carcinoma; a case report.

PMID- 15443183
TI  - Female prostatism.

PMID- 15443184
TI  - Subdiaphragmatic renal exposure by resection of the eleventh rib; a brief review
      of all previous incisions for renal exposure.

PMID- 15443185
TI  - Prostatism complicated by chronic lymphatic leukemia.

PMID- 15443186
TI  - The present status of surgical treatment of prostatic hypertrophy in Israel.

PMID- 15443187
TI  - Nomenclature of indurations of the penile tissues, with special reference to
      induration penis plastica.

PMID- 15443188
TI  - Postprostatectomy vesical neck obstruction.

PMID- 15443189
TI  - Sarcoma of the prostate: a review of the literature and case report.

PMID- 15443190
TI  - Surgical approach to the kidney.

PMID- 15443191
TI  - Anesthesia in transurethral surgery.

PMID- 15443192
TI  - The effect in biotin administration on the skin lipid secretion.

PMID- 15443193
TI  - A study of allergies to determine the origin of histamine.

PMID- 15443194
TI  - Primary carcinoma in bladder diverticula.

PMID- 15443195
TI  - Unusual problems in urologic radiology.

PMID- 15443196
TI  - Vincent's infection of the penis (erosive balanitis); differential diagnosis and
      report of a case.

PMID- 15443197
TI  - Tumor in a diverticulum of the bladder.

PMID- 15443198
TI  - Prolapse of the female urethra with strangulation and thrombosis of the urethral
      veins.

PMID- 15443199
TI  - Calculus of the lower ureter; its extraction by the retropubic route.

PMID- 15443200
TI  - Solitary renal ectopia.

PMID- 15443201
TI  - Unilateral kidney disease and hypertension.

PMID- 15443202
TI  - An unusual type of vesico-vaginal fistula and its repair using a special
      retractor.

PMID- 15443203
TI  - Scleroderma associated with malignant estrapenic leukoblastosis ("leukemia");
      case report illustrating therapeutic response to orally administered crude "B"
      fermentation concentrates.

PMID- 15443204
TI  - Treatment of psoriasis and some other skin diseases with oral undecylenic acid.

PMID- 15443205
TI  - Vasectomy in the prevention of epididymitis following prostatic surgery.

PMID- 15443206
TI  - Horseshoe kidney: report of a case with right hydronephrosis and ptosis.

PMID- 15443207
TI  - Blastomycosis of the epididymis and prostate; a case report.

PMID- 15443208
TI  - An evaluation of the various prostatic operative procedures.

PMID- 15443209
TI  - Leiomyosarcoma of the prostate: a case report.

PMID- 15443210
TI  - Multiple malignancy; report of case with synchronicity in kidney and bladder.

PMID- 15443211
TI  - Indications and arrangements for artificial insemination.

PMID- 15443212
TI  - Clinical evaluation of pennimorph.

PMID- 15443213
TI  - Periarteritis nodosa with cutaneous lesions: case report.

PMID- 15443214
TI  - A review of the newer methods of treating scabies.

PMID- 15443215
TI  - Procaine--an occupational hazard; its prevention and therapy.

PMID- 15443216
TI  - True priapism; a report of four cases and a review of the literature.

PMID- 15443217
TI  - A study of carcinoma of the prostate before and after advent of hormonal therapy.

PMID- 15443218
TI  - Is intravenous pyelography used too frequently?

PMID- 15443219
TI  - Prostatectomy--which method to select?

PMID- 15443220
TI  - Renal cortical agenesis; a case report.

PMID- 15443221
TI  - The protection afforded to the remaining healthy kidney after nephrectomy for
      tuberculosis.

PMID- 15443223
TI  - Skin diseases and pigmentation.

PMID- 15443222
TI  - Congenital diverticulum of the anterior male urethra.

PMID- 15443224
TI  - Bilateral reimplantation of the ureters into the bladder: with review of
      literature.

PMID- 15443225
TI  - Congenital anomalies of the genital and urinary tracts in Colorado General
      Hospital.

PMID- 15443226
TI  - Ectopic pelvic kidney: report of a case with hydronephrosis, calculus and
      incomplete rotation.

PMID- 15443227
TI  - Ureteral diverticulum.

PMID- 15443228
TI  - Mucin producing adenocarcinoma of the bladder associated with cystitis
      follicularis and glandularis.

PMID- 15443229
TI  - Ambulatory intensive treatment of syphilis with penicillin in oil and wax.

PMID- 15443230
TI  - Further observations on color reactions with malignant tumors.

PMID- 15443231
TI  - [Electroton and accommodation].

PMID- 15443232
TI  - [Principles of secretion and purification of antibiotics substances].

PMID- 15443233
TI  - [Immunity of pigmented plants and antibiotics].

PMID- 15443234
TI  - [Understanding of tissular cambium in contemporary histology].

PMID- 15443235
TI  - [Olfactory receptor].

PMID- 15443236
TI  - [Dehydrogenase of higher plants].

PMID- 15443237
TI  - [Ecology and physiology of submerged aquatic plants].

PMID- 15443238
TI  - [Specification of ticks in relation to their hosts].

PMID- 15443239
TI  - [Phyto-pathogenous bacteria and bacteria insect-carriers].

PMID- 15443240
TI  - Vitamin B12.

PMID- 15443242
TI  - [The hospital and psychosomatic medicine].

PMID- 15443241
TI  - [Neoplasms in cold blooded vertebrates].

PMID- 15443243
TI  - [New York's comprehensive program for continuing hospital care in the home].

PMID- 15443244
TI  - [The food in hospital diets].

PMID- 15443245
TI  - [War damage suffered by Viennese hospitals and the present status of
      reconstruction].

PMID- 15443246
TI  - [Stalin and Soviet science].

PMID- 15443247
TI  - [Stalin and progress of science in Soviet republics].

PMID- 15443249
TI  - [Stalin and historical science].

PMID- 15443248
TI  - [Stalin's theory of the state].

PMID- 15443250
TI  - [Stalin's contribution to Marx-Leninism].

PMID- 15443251
TI  - [Development of the Marxist dialectical method in the works of Stalin].

PMID- 15443252
TI  - [Stalin, creator of socialistic political economy].

PMID- 15443253
TI  - [Stalin's unicist theory of science and its practical application].

PMID- 15443254
TI  - [Stalin and Michurin's agrobiology].

PMID- 15443256
TI  - [Soviet chemistry in the Stalin era].

PMID- 15443255
TI  - [Stalin and Soviet metallurgy].

PMID- 15443257
TI  - [Contribution of Soviet scientists to the development of socialistic mechanical
      industry].

PMID- 15443258
TI  - [Soviet energetics].

PMID- 15443259
TI  - [Stalin's theory on promotion of communism].

PMID- 15443260
TI  - [Stalin's struggle for peace].

PMID- 15443261
TI  - [Exhibition in the Moscow House for scientists].

PMID- 15443263
TI  - [Constellations and origin of stars].

PMID- 15443262
TI  - [Progress of physico-mathematical sciences in the Stalin era].

PMID- 15443264
TI  - [Stalin's contribution to the progress of Soviet chemistry].

PMID- 15443265
TI  - [Progress of oil industry in the Stalin era].

PMID- 15443266
TI  - [Progress of Soviet geology].

PMID- 15443267
TI  - [Future problems of Soviet geology].

PMID- 15443268
TI  - [Stalin's contribution to the industrialization of the country].

PMID- 15443269
TI  - [Stalin's plan of reorganization of nature and Dokuchaev-Kostychev-Williams'
      theory].

PMID- 15443270
TI  - [Progress of Soviet geography in Stalin's time].

PMID- 15443271
TI  - [Progress of Soviet biology].

PMID- 15443272
TI  - [Stalin's plan of reorganization of nature in dry regions].

PMID- 15443273
TI  - [I. P. Pavlov's theory in the light of dialectic materialism].

PMID- 15443274
TI  - [Progress of mining industry in Soviet Union].

PMID- 15443275
TI  - [Contribution of Soviet scientists to the progress of fuel industry].

PMID- 15443276
TI  - [Transportation and Soviet science].

PMID- 15443277
TI  - [Radio in Soviet Union].

PMID- 15443278
TI  - [Stalin, corypheus of Marx-Leninism science].

PMID- 15443279
TI  - [Stalin's contribution to the Marx-Leninism theory of nationalism].

PMID- 15443280
TI  - [Stalin's evaluation of the importance of the party in Marx-Leninism philosophy].

PMID- 15443281
TI  - [Progress of Soviet archeology in the Stalin era].

PMID- 15443283
TI  - [Stalin's contribution to the Marx-Leninism theory of state and law].

PMID- 15443282
TI  - [Stalin, creator of political economy of socialism].

PMID- 15443284
TI  - [Stalin's theory of socialistic property].

PMID- 15443285
TI  - [Stalin, inspirer and organizer of great socialization of the land movement].

PMID- 15443286
TI  - [Stalin's contribution to the progress of literature].

PMID- 15443287
TI  - [Stalin's contribution to the basic problems of study of slavic philology].

PMID- 15443289
TI  - [Language of contemporary kolkhoz village].

PMID- 15443288
TI  - [Stalin's contribution to linguistics].

PMID- 15443290
TI  - [Stalin's contribution to the progress of literature of different nationalities
      in Soviet Union].

PMID- 15443291
TI  - [Layout of scientific research of the Academy of Science in USSR and plan for the
      education of scientific personnel for the year of 1950].

PMID- 15443292
TI  - [Plan of the Academy of Science in USSR to introduce into national economy the
      accomplished results of scientific research].

PMID- 15443293
TI  - [Flameless heating].

PMID- 15443294
TI  - [Mycorhiza of shrubs and forestation of the steppes].

PMID- 15443295
TI  - [Participation of the Academy of Science in USSR reconstruction of Moscow].

PMID- 15443296
TI  - [In memory of V. N. Obraztsov].

PMID- 15443297
TI  - [Academician V. I. Vernadskii founder of contemporary theory of optical activity
      of protoplasm].

PMID- 15443298
TI  - [Jubilee of academician A. A. Skochinskii].

PMID- 15443299
TI  - [Synonymics of coal strata].

PMID- 15443300
TI  - [Coal deposits in Kazakhstan].

PMID- 15443301
TI  - [Geological structure and perspective of oil in the vicinity of the Saratov
      region].

PMID- 15443302
TI  - [Main results of scientific work of the Academy of Science of SSSR for the year
      of 1949].

PMID- 15443303
TI  - [General meeting of the Academy of Science of SSSR dedicated to the centennial of
      the birth of S. V. Kavalevskaia].

PMID- 15443305
TI  - [Academies of Science of Soviet Union republics].

PMID- 15443304
TI  - [New linguistic theory].

PMID- 15443306
TI  - [Black Sea section of Naval Hydrophysical Institute].

PMID- 15443307
TI  - [Organization of science in France].

PMID- 15443308
TI  - [Second All Union Mechanical Conference concerning maintenance of machinery].

PMID- 15443309
TI  - [Astronomical latitudinal conference].

PMID- 15443310
TI  - [P. I. Rychkov outstanding Russian economist of XVIII century].

PMID- 15443312
TI  - [Problem of p-bodies in celestial mechanics and cosmogony].

PMID- 15443311
TI  - [Origin of planetary satellites].

PMID- 15443313
TI  - [Study of cosmic rays in stratosphere].

PMID- 15443314
TI  - [Outstanding scientist, ardent crusader for peace (50 years since the birth of
      Frederic Joliot-Curie)].

PMID- 15443315
TI  - [Nature of cosmic radiation].

PMID- 15443316
TI  - [The theory of V. R. William as an efficient weapon of Soviet agronomy].

PMID- 15443317
TI  - [Publication of new pages of Pushkin's work].

PMID- 15443318
TI  - [Ancient Russian inscriptions].

PMID- 15443319
TI  - [Congress on chemistry and on the genesis of solid combustible minerals].

PMID- 15443320
TI  - [Congress on control of pests and diseases of forested regions].

PMID- 15443321
TI  - [Founder of Soviet topology P. S. Uryson (25 years since his death)].

PMID- 15443322
TI  - [Jubilee of academician G. S. Landsberg].

PMID- 15443323
TI  - [Structure of Ukrainian crystal massive].

PMID- 15443324
TI  - [Volcanism in Georgia].

PMID- 15443325
TI  - [Littoral granite and its relation to metallogeny].

PMID- 15443326
TI  - [Factors in equilibrium in metasomatosis].

PMID- 15443327
TI  - [Lenin and progress of communism].

PMID- 15443328
TI  - [Malthusian theory in the service of American imperialism].

PMID- 15443329
TI  - [Predecessor of Michurin's theory (30 years since the death of K. A.
      Timiriazev)].

PMID- 15443330
TI  - [Best, most talented poet of our time (sessions dedicated to the memory of V. V.
      Maiakovskii)].

PMID- 15443331
TI  - [In defense of Joliot-Curie].

PMID- 15443332
TI  - [Academy of Science of the Rumanian republic].

PMID- 15443333
TI  - [Three hundred years since the death of Rene Descartes].

PMID- 15443334
TI  - [Philosophy of Rene Descartes].

PMID- 15443336
TI  - [Conference on the problems of harvest].

PMID- 15443335
TI  - [Descartes' theory on natural science].

PMID- 15443337
TI  - [Conference on forest typology].

PMID- 15443338
TI  - [First all union congress of botanists and selectionists].

PMID- 15443339
TI  - [Unpublished materials on the expedition of N. N. Miklukho-Maklaia into the basin
      of the Red Sea].

PMID- 15443340
TI  - [Jubilee of B. N. Delone].

PMID- 15443342
TI  - [Gaseous train of the earth].

PMID- 15443341
TI  - [Certain results of the study of hydrogen radiations in galactic nebula].

PMID- 15443343
TI  - [Prevention and development of cancer].

PMID- 15443344
TI  - [Preoperative sterilization of hands and gloves with chloramine solution].

PMID- 15443346
TI  - [Vitreous body as a stimulant in complex therapy of cicatricial contractures of
      the extremities].

PMID- 15443345
TI  - [Intracardiac blood transfusion].

PMID- 15443347
TI  - [Modifications in the remaining lung following partial or total excision of the
      other].

PMID- 15443348
TI  - [Strangulation of inguinal hernia in children].

PMID- 15443349
TI  - [Modification in plastic surgery of inguinal hernia].

PMID- 15443350
TI  - [Total plastic surgery of the penis and urethra by means of two Filatov's flaps].

PMID- 15443351
TI  - [Several cases of treatment of false joints without involving the false joint
      proper].

PMID- 15443352
TI  - [Traumatic aseptic necrosis of the head of the femur].

PMID- 15443353
TI  - [Appliance for one-stage reduction of dislocated fragments in fractures of the
      humerus].

PMID- 15443354
TI  - [Surgical treatment of osteoarticular tuberculosis in Bulgaria].

PMID- 15443355
TI  - [The distinguised Russian scientist Vasilii Vasil'evich Chirkovskii].

PMID- 15443356
TI  - [Scientific research on the etiology and pathogenesis of trachoma since the
      October Revolution].

PMID- 15443357
TI  - [Histologic studies on the preservation of rabbit's cornea by means of
      refrigeration].

PMID- 15443358
TI  - [Effect of certain concomitant general diseases on the course of trachoma].

PMID- 15443359
TI  - [Surgical therapy of glaucoma; results of one modification of Lagrange's surgical
      method].

PMID- 15443361
TI  - [Priority of Russian authors in ophthalmology in plastic surgery].

PMID- 15443360
TI  - [Studies on homonymous hemianopsia in high blood pressure].

PMID- 15443362
TI  - [Some remarks on bibliography on ophthalmology and advances of Russian oculists].

PMID- 15443363
TI  - [Modifications of eye fundus and evaluation of working capacity in hypertension].

PMID- 15443364
TI  - [Certain forms of ophthalmological diseases in hypertension].

PMID- 15443365
TI  - [Results of elastotonometry according to Kalfa in hypertension].

PMID- 15443366
TI  - [Skin tests as a diagnostic method of allergic medicamentous dermatitis].

PMID- 15443367
TI  - [Oculoglandular form of listerellosis].

PMID- 15443368
TI  - [Respiration of living and preserved cornea].

PMID- 15443369
TI  - [Injections of vitreous body in treatment of cicatricial modifications].

PMID- 15443370
TI  - [Novocain block in treatment of certain forms of keratitis].

PMID- 15443371
TI  - [Answer to the article of E. M. Rakhal'skaia "Tenomyoectomy as a method of
      surgical treatment marked concomitant strabismus"].

PMID- 15443372
TI  - [Report on therapeutic work and classification of case histories in
      ophthalmological clinics].

PMID- 15443373
TI  - [Ophthalmologic service in central and regional hospitals].

PMID- 15443374
TI  - [New method in application of corneal sutures].

PMID- 15443375
TI  - [A method of detection of simulation of diminished visual field].

PMID- 15443376
TI  - [Ophthalmological kit].

PMID- 15443377
TI  - [Two cases of gadfly larva in the conjunctival sac of the human eye].

PMID- 15443378
TI  - [Affection of vestibular apparatus as a symptom of plasmocide atrophy of optical
      nerves].

PMID- 15443379
TI  - [Clinical manifestations of neurinoma of the acoustic nerve from the
      otoneurologic view point].

PMID- 15443380
TI  - [Role of cerebral cortex in manifestations of vestibular reflexes].

PMID- 15443381
TI  - [Localized meningo-encephalitis].

PMID- 15443382
TI  - [Certain data on the role of Russian scientists of the second half of XIX century
      in the progress of labyrinthology].

PMID- 15443383
TI  - [Modifications of intracranial pressure in dogs following frequent cisternal
      punctures].

PMID- 15443384
TI  - [Streptomycin therapy of tuberculosis of pharynx, larynx and oral cavity].

PMID- 15443386
TI  - [Pathological anatomy of laryngeal papilloma].

PMID- 15443385
TI  - [Cytological diagnosis of upper respiratory tract and mouth diseases].

PMID- 15443387
TI  - [Treatment of certain forms of deafness by transplant of preserved tissue of
      aloe].

PMID- 15443388
TI  - [Modification of intra-aural radical surgery].

PMID- 15443389
TI  - [Use of dental burs in otorhinolaryngeal surgery].

PMID- 15443390
TI  - [Paracentesis in toxic dyspepsia in children].

PMID- 15443391
TI  - [Dacryocystitis in newborn and early childhood and its treatment by means of
      retrograde probing].

PMID- 15443392
TI  - [Treatment of tuberculosis of the upper respiratory tract by local injections of
      streptomycin].

PMID- 15443393
TI  - [Rare complication following adenotomy].

PMID- 15443394
TI  - [Cases of intracranial complications following surgery of the nasal cavity].

PMID- 15443395
TI  - [Pedicled sarcoma of the palatine tonsil].

PMID- 15443396
TI  - [Fibrolipoma of the tonsil].

PMID- 15443397
TI  - [Cancer of the larynx in a girl 15 years of age].

PMID- 15443398
TI  - [Bronchial stenosis of tuberculous origin].

PMID- 15443399
TI  - [Case of protracted lodging of a large foreign body in the bronchus].

PMID- 15443400
TI  - [Instruments for esophagoscopy and bronchoscopy].

PMID- 15443401
TI  - [Improvement of the broncho-esophagoscope].

PMID- 15443402
TI  - [Derzhne's correctophone and Barany's apparatus].

PMID- 15443403
TI  - [NIKOLAI Petrovich Mikhalkin].

PMID- 15443404
TI  - [Contemporary treatment of otogenic cerebral abscesses].

PMID- 15443405
TI  - [Practical application of Pavlov's theory of the role of the nervous system in
      the progress of dermatology].

PMID- 15443406
TI  - [Effect of small doses of roentgen rays on the brain of the newborn].

PMID- 15443407
TI  - [Experimental study of staphylococcic toxins and antitoxins].

PMID- 15443408
TI  - [Phagocytic activity of blood in staphyloderma].

PMID- 15443409
TI  - [Antiphagin treatment of staphyloderma].

PMID- 15443410
TI  - [Therapeutic use of antiphagin in pyoderma].

PMID- 15443411
TI  - [Effect of penicillin in gonorrhea].

PMID- 15443412
TI  - [Case of trichosporosis nodosa (piedra)].

PMID- 15443413
TI  - [Treatment of onychomycosis].

PMID- 15443414
TI  - [Penicillin combined with autoblood in treatment of pyoderma].

PMID- 15443415
TI  - [Staphylococcic antiphagin treatment of pyoderma in coal miners].

PMID- 15443416
TI  - [Combination of scabies with syringomyelia].

PMID- 15443417
TI  - [Penicillin salve].

PMID- 15443418
TI  - [Use of Gordeev's solution in dermatology].

PMID- 15443419
TI  - [Selebin new preparation in treatment of eczema].

PMID- 15443420
TI  - [Complications and side effects in penicillin treatment].

PMID- 15443421
TI  - [Ozocerite treatment of skin diseases].

PMID- 15443422
TI  - [Necrotic degeneration of lymphogranulomatous nodes and the ulceration of the
      adjacent skin].

PMID- 15443423
TI  - [American leishmaniasis].

PMID- 15443424
TI  - [Penicillin in autoblood in treatment of gonorrhea].

PMID- 15443425
TI  - [Luminescent method in early diagnosis of microsporia].

PMID- 15443426
TI  - The importance to the community of the control of diseases inimical to man.

PMID- 15443427
TI  - Immunisation against rinderpest by lapinised virus.

PMID- 15443428
TI  - Experiences in the Antarctic.

PMID- 15443429
TI  - "Caricide" in the treatment of Dirofilaria immitis in Zanzibar.

PMID- 15443430
TI  - [Fracture of the neck of the femur].

PMID- 15443431
TI  - [Case of adenoma of the adrenals].

PMID- 15443432
TI  - [Importance of the anamnestic reaction in fetal-maternal conflict].

PMID- 15443433
TI  - [Rectosigmoid cancer].

PMID- 15443434
TI  - [Present treatment of parkinsonism].

PMID- 15443435
TI  - [The diagnosis of adrenal insufficiency of serum origin can be easy and exact].

PMID- 15443436
TI  - [The Black Crusade of Health].

PMID- 15443437
TI  - [Inositol, vitamin and growth factor].

PMID- 15443438
TI  - [Treatment of diseases of rheumatic origin].

PMID- 15443439
TI  - [Action of calcium nicotate on the utilization of ingested calcium and vitamin C
      by the organism].

PMID- 15443440
TI  - [Health education by motion pictures].

PMID- 15443441
TI  - [The variations of Dr. O'Grady, alienist].

PMID- 15443442
TI  - [Severe generalized arteritis in serum sickness in man].

PMID- 15443443
TI  - [Effect of alloxan in fish].

PMID- 15443444
TI  - [A dicephalotribrachious monster].

PMID- 15443445
TI  - [Problem of the mesencephalo-hypophyseal system; experiments on the cat].

PMID- 15443446
TI  - [Position and function of the vasomotor center in the medulla oblongata,
      according to findings in poliomyelitis].

PMID- 15443447
TI  - [Fatty arterial gas embolism (gas-fat embolism) in experiments on rabbits].

PMID- 15443448
TI  - [Comparative investigation of homotransplantation of auricular cartilage and
      benzpyrene sarcoma in rats].

PMID- 15443449
TI  - [Heterotopic pancreatic cells in the pyloric glands in man].

PMID- 15443450
TI  - [Modifications of the pulmonary hilus due to age].

PMID- 15443451
TI  - [Peculiar distribution of blood in the liver; peripheral hyperemia of the hepatic
      acini].

PMID- 15443452
TI  - [Pathogenesis of early atherosclerotic modifications of the aorta].

PMID- 15443453
TI  - [Blood vessels of the human penis; a contribution to the physiology and pathology
      of the regulatory systems of the peripheral circulation].

PMID- 15443454
TI  - [Generalized xanthomatosis with affection of the bone and diffuse plasma cell
      proliferation in the bone-marrow in essential hyperlipemia].

PMID- 15443456
TI  - [Vacuolar degeneration of liver cells].

PMID- 15443455
TI  - [Reflux of bile into the pancreatic ducts].

PMID- 15443457
TI  - Management of delirium in the general hospital.

PMID- 15443458
TI  - Treatment of lower nephron nephrosis by intestinal lavage.

PMID- 15443459
TI  - Sarcoidosis.

PMID- 15443460
TI  - Preinvasive carcinoma of the cervix: an opportunity to reduce cancer mortality.

PMID- 15443461
TI  - Bromide intoxication; report of 12 cases.

PMID- 15443462
TI  - Cushing's syndrome: report of 2 cases.

PMID- 15443463
TI  - CLINICOPATHOLOGICAL reports; dissecting aneurysm of aorta; medial necrosis of
      aorta; myocardial hypertrophy.

PMID- 15443464
TI  - Public health.

PMID- 15443465
TI  - Medicine in industry and its influence on medical care.

PMID- 15443466
TI  - Child guidance clinics.

PMID- 15443467
TI  - Interrelationships of medicine and speech pathology.

PMID- 15443468
TI  - Lipoid pneumonia due to the use of mineral oil as a laxative.

PMID- 15443469
TI  - Obstetrical factors in infant mortality.

PMID- 15443470
TI  - Tuberculosis control program in a general hospital.

PMID- 15443471
TI  - CLINICOPATHOLOGICAL reports; acute caseous tuberculosis bronchopneumonia;
      disseminated acute caseous tuberculosis (miliary) involving liver, spleen,
      adrenal, thyroid and pancreas.

PMID- 15443472
TI  - Public health.

PMID- 15443473
TI  - [Principal problems in tissue-extract therapy].

PMID- 15443474
TI  - [Present status of surgical treatment of injuries of the spinal cord and cauda].

PMID- 15443475
TI  - [Surgery of the rectum].

PMID- 15443476
TI  - [Treatment of acute otorhinolaryngologic complications with penicillin].

PMID- 15443477
TI  - [Fatigue and its prevention].

PMID- 15443478
TI  - [Relation of alcohol to road accidents].

PMID- 15443479
TI  - [Epidemic poliomyelitis and treatment with massive doses of pyramidon].

PMID- 15443480
TI  - [Hygienic memorandum on rehabilitation in german housing].

PMID- 15443481
TI  - [Genetics of microorganisms].

PMID- 15443482
TI  - [Genetics of bacteria].

PMID- 15443483
TI  - [Antibiotics].

PMID- 15443484
TI  - [Penicillin production and determination].

PMID- 15443485
TI  - [Further researches on natural organ-specific antibiotics (inhibins)].

PMID- 15443487
TI  - [Electronoptic photographs of the tubercle bacillus].

PMID- 15443486
TI  - [Experience with penicillin and streptomycin determination by spores].

PMID- 15443488
TI  - [Nutrition physiology of dysentery bacteria].

PMID- 15443489
TI  - [Bacterial induction of serological properties].

PMID- 15443490
TI  - [Metabolic studies of the pathogens of endocarditis].

PMID- 15443491
TI  - [Morphologic investigation of living streptococci by means of phase contrast
      microscopy].

PMID- 15443492
TI  - [Water metabolism and mineral salt excretion in liver disease and the effect of
      desoxycorticosterone].

PMID- 15443493
TI  - [Effect of hexestrol implantation upon metabolism and endocrine organs of the
      female rat].

PMID- 15443494
TI  - [Allergic reactions of the skin to antigens of the vaccinia-variola group].

PMID- 15443495
TI  - [Fatal gastroenterocolitis of unusual bacterial origin in a child].

PMID- 15443496
TI  - [Kux's endoscopic transthoracic sympathectomy and intratracheal anesthesia].

PMID- 15443497
TI  - [A few diagnostic principles].

PMID- 15443498
TI  - [Prof. Dr. med. Karl Schuhecker].

PMID- 15443499
TI  - [Rickettsial disease in Vienna].

PMID- 15443500
TI  - [Streptomycin therapy of tuberculous meningitis in childhood].

PMID- 15443501
TI  - [Thrombophlebitis saltans and phlebothrombosis].

PMID- 15443502
TI  - [Acidity and ulcer; pH studies of the ulcerous stomach].

PMID- 15443503
TI  - [Hemorrhagic states].

PMID- 15443504
TI  - [Renal function in the light of modern experimental methodology].

PMID- 15443505
TI  - [Intravenous thrombokinase therapy].

PMID- 15443506
TI  - [Bacteriology of the ulcerous stomach and its lymphatic system, and its surgical
      significance].

PMID- 15443507
TI  - [Atypical epileptic manifestations].

PMID- 15443508
TI  - [Experience with mapharsen].

PMID- 15443509
TI  - [Murphy's button in abdominal resection of the rectum].

PMID- 15443510
TI  - [Observation of the author and of Dutch writers on smallpox and postvaccinal
      encephalitis].

PMID- 15443511
TI  - [Water metabolism and mineral salt excretion in liver disease and the effect of
      desoxycorticosterone].

PMID- 15443512
TI  - [Ligation of the superior caval vein].

PMID- 15443513
TI  - [Roentgenography of phlegmon of the small intestine].

PMID- 15443514
TI  - [Reducing with analeptic amines].

PMID- 15443515
TI  - [Multiple exostoses of the spinal column in acromegaly].

PMID- 15443516
TI  - [Water metabolism and mineral salt excretion in liver disease and the effect of
      desoxycorticosterone].

PMID- 15443517
TI  - [Preliminary ligation of the superior thyroid vessels in surgery of excessively
      large goiter].

PMID- 15443518
TI  - [Ultrasonic therapy of thrombosis and embolism].

PMID- 15443519
TI  - [Favorable and untoward results of neurosurgery in children].

PMID- 15443520
TI  - [Hypoproteinemia in pernicious anemia].

PMID- 15443521
TI  - [Addison's disease and appendicitis].

PMID- 15443522
TI  - [History of the Vienna Medical School].

PMID- 15443523
TI  - [Sciatica or rupture of a transverse process; diagnosis of athletic injuries of
      the lumbar spine].

PMID- 15443524
TI  - [Conservative therapy of renal tuberculosis].

PMID- 15443525
TI  - [Atypical clinical aspects of extramedullary constrictive processes; broadened
      scope of indications for myelography and exploratory laminectomy].

PMID- 15443526
TI  - [Favorable and untoward results of neurosurgery in children; tumors of the
      cerebral hemispheres].

PMID- 15443527
TI  - [Recent methods of anesthesia in otolaryngologic surgery].

PMID- 15443528
TI  - [Epidemiology of rabies in Austria].

PMID- 15443529
TI  - [Significance of albuminuria in diabetes mellitus].

PMID- 15443530
TI  - [Anuria and uremia due to sulfonamide intoxication].

PMID- 15443531
TI  - [Favorable and untoward results of neurosurgery in children].

PMID- 15443532
TI  - [Collateral effects of penicillin and streptomycin therapy].

PMID- 15443533
TI  - [A new method of artificial respiration, the electric lung].

PMID- 15443534
TI  - [Classification and treatment of arterial hypertension].

PMID- 15443535
TI  - [Antibiotics of low solubility].

PMID- 15443536
TI  - [Suboccipital puncture and its dangers].

PMID- 15443537
TI  - [Use of thrombin in neurosurgery].

PMID- 15443538
TI  - [Leukocytosis in pregnancy, labor and puerperium].

PMID- 15443539
TI  - [Treatment of toxic granulocytopenia].

PMID- 15443540
TI  - [Bronchial asthma, a biochemical hormonal regulation disorder].

PMID- 15443541
TI  - [Experience with a new analgesic in surgery].

PMID- 15443542
TI  - [Treatment of oxyuriasis].

PMID- 15443543
TI  - [In memoriam Carl Ewald].

PMID- 15443544
TI  - Vitamin B12.

PMID- 15443545
TI  - [A case of endometriosis].

PMID- 15443546
TI  - [Etiology, therapy and prevention of goiter].

PMID- 15443547
TI  - [Bronchopulmonary segment diagnosis].

PMID- 15443548
TI  - [Postoperative peritonitis and disorders of stomach evacuation following
      gastrectomy for peptic ulcer; differential diagnosis, therapy and prophylaxis].

PMID- 15443549
TI  - [Diffuse purulent peritonitis in acute otitis media].

PMID- 15443550
TI  - [Recurrent goiter and thiouracil; local and vicarious relapse].

PMID- 15443551
TI  - [Treatment of turrecephaly with Wanke's vertical craniotomy].

PMID- 15443552
TI  - [Treatment of tuberculous empyema and exudation with p-aminosalicylic acid].

PMID- 15443553
TI  - [Significance of the sympathetic nervous system in epileptic attacks].

PMID- 15443555
TI  - [Carcinoma of the small intestine].

PMID- 15443554
TI  - [Sarcoma of the small intestine].

PMID- 15443556
TI  - [Perforation of the heart by a fractured rib].

PMID- 15443557
TI  - [Etiology of edema in acute glomerulonephritis, particularly in war nephritis].

PMID- 15443558
TI  - [Indications for radical surgery in cancer of the rectum and pelvic colon].

PMID- 15443559
TI  - [Treatment of perforating ulcer].

PMID- 15443560
TI  - [Remarkable increase in macrocytic anemias of the pernicious type following the
      first and second world wars].

PMID- 15443561
TI  - [Polycystic kidney in an 18 month old infant].

PMID- 15443562
TI  - [Treatment of gastric and duodenal ulcer with sodium benzoate (dextroben)].

PMID- 15443563
TI  - [Treatment of prostate cancer with retarded-action estrogen].

PMID- 15443564
TI  - [Treatment of gastric and duodenal ulcer with robuden].

PMID- 15443565
TI  - JOINT Office International d'Hygiene Publique/World Health Organization study
      group on bilharziasis in Africa.

PMID- 15443566
TI  - [Studies of diplomycin and its use in general practice].

PMID- 15443567
TI  - [Dental use of penicillin preparations for retarded action].

PMID- 15443568
TI  - [Cysts of the nasopalatine duct; case reports and operative methods].

PMID- 15443569
TI  - [Fatal thyrvonine anesthesia].

PMID- 15443570
TI  - [Indications for hinged clasps].

PMID- 15443571
TI  - [Summary of Prof. Euler's lecture in Berlin].

PMID- 15443572
TI  - [Prof. Kantorowicz on his 70th birthday].

PMID- 15443573
TI  - [Effect of early loss of teeth in inhibiting the growth of the apical base and
      facial skeleton].

PMID- 15443574
TI  - [Alfred Kantorowicz and planned dental service in schools].

PMID- 15443575
TI  - [Possibilities of widening the dental arch].

PMID- 15443576
TI  - [Maxillary orthopedics in planned dental service for schools].

PMID- 15443577
TI  - [Maxillary orthopedics and early treatment in pedodontia].

PMID- 15443578
TI  - [A general practitioner's point of view on nitrous oxide anesthesia].

PMID- 15443579
TI  - [Pivot and post crowns with Palapont-Rapid].

PMID- 15443581
TI  - [Practicability of the British National Health Service Act].

PMID- 15443580
TI  - [Afraid of the dentist].

PMID- 15443582
TI  - [Possibilities and limitations in treatment of the devitalized tooth].

PMID- 15443583
TI  - [The ring in crownwork].

PMID- 15443584
TI  - [Penicillin in dentistry].

PMID- 15443585
TI  - [Acute inflammation of the temporomandibular joint treated with impletol].

PMID- 15443586
TI  - [Roentgenography of the capitulum mandibulae].

PMID- 15443587
TI  - [Surgical therapy of paradentosis].

PMID- 15443588
TI  - [Casting acrylic crowns in the mouth with use of translucent odus-acryl-crowns].

PMID- 15443589
TI  - [Silicon].

PMID- 15443590
TI  - [Intradental foci].

PMID- 15443591
TI  - [Surgery, especially extraction, in the course of conservative therapy].

PMID- 15443592
TI  - [General practice and focal infection].

PMID- 15443593
TI  - [The dentist's role in the treatment of arthritis].

PMID- 15443594
TI  - [The problem of root canal therapy].

PMID- 15443595
TI  - [Problem of dental asepsis].

PMID- 15443596
TI  - [Death of dental pulp following silicate filling].

PMID- 15443598
TI  - [Enterococci].

PMID- 15443597
TI  - [Conduction anesthesia in the maxilla].

PMID- 15443599
TI  - [Reorganization of the health service in Czechoslovakia].

PMID- 15443600
TI  - [Public health personnel in Czechoslovakia].

PMID- 15443601
TI  - [Statistics of mortality, invalidity and morbidity at the beginning of the new
      plan of health service].

PMID- 15443602
TI  - [Work of the public health section of the National Regional Committee].

PMID- 15443603
TI  - [Socialization of medicine].

PMID- 15443604
TI  - [Socialization of medicine in Czechoslovakia].

PMID- 15443605
TI  - [Hygiene of living quarters in relation to epidemiology].

PMID- 15443606
TI  - [Control of social diseases and care of mother and child].

PMID- 15443607
TI  - [Medical legislation in Czechoslovakia].

PMID- 15443608
TI  - [Drugs and pharmaceutical preparations].

PMID- 15443609
TI  - [Training of medical personnel].

PMID- 15443610
TI  - [Legislations concerning public health].

PMID- 15443611
TI  - [Enlarged pneumonolysis].

PMID- 15443612
TI  - [Is cancer a viral disease?].

PMID- 15443613
TI  - [Accident prevention].

PMID- 15443614
TI  - [Infections in children homes].

PMID- 15443615
TI  - [Critical review of the Social Security, especially of its physicians].

PMID- 15443616
TI  - [Obligatory registration of malignant tumors].

PMID- 15443617
TI  - [Obligatory registration of puerperal sepsis].

PMID- 15443618
TI  - [Treatment of traumatic shocks].

PMID- 15443619
TI  - [New methods and progress in internal therapy].

PMID- 15443620
TI  - [Requalification in the organization of social security].

PMID- 15443621
TI  - [Local and active treatment of adnexitis].

PMID- 15443622
TI  - [History of obstetrics in Slovenia].

PMID- 15443623
TI  - [Medical bibliography in Yugoslavia].

PMID- 15443624
TI  - [Shortcomings in syphilis therapy].

PMID- 15443625
TI  - [New viewpoints in the evaluation of roentgenotherapy of genital carcinoma;
      reaction of the serous membrane in genital tumors, with special reference to
      systemic carcinoma].

PMID- 15443626
TI  - [Biocytologic diagnosis of cancer; phase contrast studies in Papanicolaou's
      method].

PMID- 15443627
TI  - [Premenstrual disorders, autonomic nervous system, and normal menstrual cycle].

PMID- 15443628
TI  - [Extraction of Rh haptens from human blood and urine].

PMID- 15443629
TI  - [Staub-Traugott test and sero-chemical modifications in diabetics].

PMID- 15443630
TI  - [Permeability of the rat placenta to thorium ions at different stages of
      pregnancy; contribution to the use of isotopes in medicine].

PMID- 15443631
TI  - [Thorium behaviour in pregnant and non-pregnant rats; contribution to the use of
      isotopes in medicine].

PMID- 15443632
TI  - [Effect of a pancreatic peptone on the growth and weight of protein-deficient
      rats].

PMID- 15443633
TI  - [Effect of dibromosalicil upon staphylococci].

PMID- 15443634
TI  - [Effect of sulfonamides on histamine metabolism].

PMID- 15443635
TI  - [Action mechanism of marfanil].

PMID- 15443636
TI  - [The problem of cutaneous loss of water, and methods for its determination].

PMID- 15443637
TI  - [Relation of cutaneous loss of water and skin temperature in various parts of the
      body to heat regulation].

PMID- 15443638
TI  - [Comparative investigations of the effect of adrenalin and arterenol on
      circulation].

PMID- 15443639
TI  - [Treatment of experimental nephritis (Masugi nephritis) and anaphylactic shock
      with benadryl (beta-di-methylaminoethyl benzohydryl ether)].

PMID- 15443640
TI  - [Determination of ketogenic prehypophyseal hormone].

PMID- 15443641
TI  - [Technicophysical aspects of methods heretofore used in medicine for the
      determination of creatine bodies, with observations on the precipitation and
      separation of creatine and creatinine; presentation of specifications for a
      photoelectric wedge colorimeter].

PMID- 15443642
TI  - [Electrophoretic examination of blood protein bodies in pulmonary tuberculosis
      treated with TB I].

PMID- 15443643
TI  - [Experiments on the effect of TB I; manifestations of intoxication].

PMID- 15443644
TI  - [Experiments on the effect of TB I; investigation of the amino acids of serum and
      tissue protein during intoxication with TB I].

PMID- 15443645
TI  - [Structural analysis of serum and tissue protein in the normal and undernourished
      dog].

PMID- 15443646
TI  - [Endogenous creatine clearance in the normally nourished dog].

PMID- 15443647
TI  - [Effect of vitamin B1 upon renal excretion of sodium].

PMID- 15443648
TI  - [Investigations in the problem of the ovum hormone].

PMID- 15443649
TI  - [Enterotropic action of bivalent and trivalent alcohols].

PMID- 15443650
TI  - [Experimental hemolytic anemias and their course following splenectomy].

PMID- 15443651
TI  - [Formation of ketone bodies from amino acids; behavior of the so-called
      ketogenous amino acids of the myocardium].

PMID- 15443652
TI  - [Recent results in research on the biochemistry of the tubercle bacillus; review
      of the literature].

PMID- 15443653
TI  - [Quantitative tuberculin test with purified protein derivative].

PMID- 15443654
TI  - [Arterial function tests of the upper extremities with simultaneous anesthesia of
      the median and ulnar nerves].

PMID- 15443655
TI  - [New case of Pelger-Huet nuclear anomaly].

PMID- 15443656
TI  - [Diagnosis of cancer of the lung; symptomatology and pathology of certain forms
      of extrapulmonary infiltration].

PMID- 15443657
TI  - [Results of penicillin therapy in agranulocytosis].

PMID- 15443658
TI  - [Investigations of survival time of transfused erythrocytes in internal diseases
      and hemolytic syndromes].

PMID- 15443659
TI  - [New multiple electrode for the precordial electrocardiogram].

PMID- 15443660
TI  - [Nomenclature of precordial leads].

PMID- 15443661
TI  - [Specificity in serological investigations of cancer].

PMID- 15443662
TI  - [Serum and tissue disinfection with kollidon; experiments on the rabbit with
      diamine blue FF].

PMID- 15443663
TI  - [Appearance of uroporphyrin in the urine].

PMID- 15443664
TI  - [Unusual observations on allergic diseases].

PMID- 15443665
TI  - [Takata reaction and other lability reactions of the serum in dogs and rats, and
      their relation to liver function].

PMID- 15443666
TI  - [Thoughts on life, age sickness and death from the standpoint of the body's
      development].

PMID- 15443667
TI  - [Endemic paratyphoid-A during the regression of a typhoid epidemic, with
      observations on the typhoid problem].

PMID- 15443668
TI  - [Motor mechanics in the tubular structures of the human body].

PMID- 15443669
TI  - [A clinical test of antimitotic poisons].

PMID- 15443671
TI  - [Prognosis in valvular disease of the heart].

PMID- 15443670
TI  - [Anatomopathological investigations on the frequency of supernumerary renal
      vessels, and hydronephrosis of vascular origin].

PMID- 15443672
TI  - [Morphologic modifications of the blood picture during the postwar period].

PMID- 15443673
TI  - [Effect of irritation of the central nervous system upon mineral metabolism].

PMID- 15443674
TI  - [Mitotic phases in the peripheral blood in leukemia treated with cytostatic
      substances].

PMID- 15443675
TI  - [Pernicious and perniciosiform anemias during the postwar period].

PMID- 15443676
TI  - [Phase contrast microscope; attempt at an explanation without the use of
      mathematical formulas].

PMID- 15443677
TI  - [Cystine content of normal and pathologic serum proteins].

PMID- 15443678
TI  - [Investigation of the chemical method in the determination alpha-, beta-, and
      gamma-globulins and albumins in two cc of serum, and its applications in
      diagnosis of diseases of the liver].

PMID- 15443679
TI  - [Possibility of intratesticular administration of testosterone crys tal
      emulsions].

PMID- 15443680
TI  - [Right-sided hiatus hernia; contribution to the problem of the reactions of the
      autonomic nervous system].

PMID- 15443681
TI  - [Hemolytic anemia and autoagglutination; contribution to the causal significance
      of abnormal serologic reactions].

PMID- 15443682
TI  - [Unsuccessful liver therapy in pernicious anemia complicated by diseases of the
      bone].

PMID- 15443683
TI  - [Problem of the typical blood picture in influenza].

PMID- 15443684
TI  - [Quantitative analysis of p-oxyphenylpyroracemic acid by means of chromatographic
      adsorption in liver disease].

PMID- 15443685
TI  - [Neural regulation of carbohydrate metabolism].

PMID- 15443686
TI  - [A case of leprosy].

PMID- 15443687
TI  - [Pathogenesis and clinical aspects of onycholysis semilunaris partialis].

PMID- 15443688
TI  - [On consideration of total aspect in dermatology].

PMID- 15443689
TI  - [Pyrifer as an antigen in bacterial autoallergy].

PMID- 15443690
TI  - [Use of neat's-foot oil in cosmetic dermatology].

PMID- 15443691
TI  - [Treatment of pruriginous affections of the anus].

PMID- 15443692
TI  - [Penicillin therapy of gonorrhea complicated by syphilis].

PMID- 15443693
TI  - [Skin and psyche].

PMID- 15443694
TI  - [Cutaneous allergic manifestations and constitution].

PMID- 15443695
TI  - [Keratosis palmaris et plantaris with affection of the nails and mucosa].

PMID- 15443696
TI  - [Chronic pyoderma].

PMID- 15443697
TI  - [Syphilis of the third generation].

PMID- 15443698
TI  - [Mibelli porokeratosis (illustration)].

PMID- 15443699
TI  - [Effect of simultaneous application of salvarsan upon efficacy of penicillin].

PMID- 15443700
TI  - [Medicinal thallium poisoning].

PMID- 15443701
TI  - [Effect of antihistamines in prophylaxis of allergic reactions].

PMID- 15443702
TI  - [Xeroderma pigmentosum].

PMID- 15443703
TI  - [Dermatotic cataract].

PMID- 15443704
TI  - [Extraction of foreign bodies imbedded in the skin].

PMID- 15443705
TI  - [Penicillin therapy of interstitial keratitis during the first month of life].

PMID- 15443706
TI  - [Comment on the article, Serologic reactions in syphilis, and personal experience
      with cardiolipin as the antigen].

PMID- 15443707
TI  - [Treatment of sexual disorders in the male].

PMID- 15443708
TI  - [Portraits of dermatologists and venereologists on postage stamps].

PMID- 15443709
TI  - [Can antibodies be antigenic?].

PMID- 15443711
TI  - [Effect of human serum upon chronic nagana in rats].

PMID- 15443710
TI  - [The ice cream industry; problem of supervision of the manufacture and sale of
      ice cream and similar products].

PMID- 15443712
TI  - [Origin of inhibitors of the influenza virus in normal human serum].

PMID- 15443713
TI  - [Further research in biology and serology of streptococci (groups A, B, and C)].

PMID- 15443714
TI  - [Epidemiologic and statistical investigation on the spread of oxyuriasis].

PMID- 15443715
TI  - [Investigations on the coagulation reaction of Hirschfeld and Klinger as a
      serological diagnosis of syphilis].

PMID- 15443716
TI  - [Methods of testing sporicidal solutions].

PMID- 15443717
TI  - [Solution of the problem of surgical sterilization with sporil, without
      sterilizer].

PMID- 15443718
TI  - [Problem of the intermediary type of the A blood group].

PMID- 15443719
TI  - [A mannite-positive, Shigella-like strain, with serological relation to Large
      Sachs type Q 771].

PMID- 15443720
TI  - [Microbiologic diagnosis of obligate and facultative pathogenic gram-negative
      bacteria in infections of the intestinal and urogenital tracts].

PMID- 15443721
TI  - [Work shoes].

PMID- 15443722
TI  - [Induced mutations in Leptospira].

PMID- 15443724
TI  - [Epidemiology of typhus].

PMID- 15443723
TI  - [Comparative investigations of certain new culture mediums for the isolation of
      Salmonella and Shigella].

PMID- 15443725
TI  - [Experimental transmission of the pathogenic spirochetes of relapsing fever
      through Ornithodorus moubata].

PMID- 15443726
TI  - [Investigations on the control of industrial anthrax; germicidal effect of sodium
      sulfide, sodium hydrosulfide, hydrogen sulfide, and milk of lime combined with
      sodium sulfide upon anthrax spores at different temperatures].

PMID- 15443727
TI  - [An antibiotic derived from the cocci of human saliva].

PMID- 15443728
TI  - [In vitro experiments on the synergistic action of streptomycin and
      sulfonamides].

PMID- 15443729
TI  - [Contagious diseases and their control among the young conscripts of the former
      Male Labor Corps before and during the last war].

PMID- 15443730
TI  - [Occurrence of Escherichia coli, Aerobacter aerogenes and intermediate forms in
      the blood].

PMID- 15443731
TI  - [Transmission of ova of parasitic worms by paper money].

PMID- 15443732
TI  - [In vitro examination of tuberculostatic substances].

PMID- 15443733
TI  - [Hospitalism today].

PMID- 15443734
TI  - [The nature of the urobilinogenuria of scarlet fever].

PMID- 15443735
TI  - [Diagnosis of whooping cough in infants from the white blood picture].

PMID- 15443736
TI  - [Bilateral spontaneous pneumothorax in congenital cystic lung].

PMID- 15443737
TI  - [Pheochromocytoma in childhood and its relation to high blood pressure].

PMID- 15443738
TI  - [Function of the adrenal cortex in acute and chronic diseases of childhood;
      diagnosis of latent adrenocortical insufficiency].

PMID- 15443739
TI  - [Function of the adrenal cortex in acute and chronic diseases of childhood;
      modifications of adrenocortical function during the course of acute, atoxic
      infectious diseases, with especial reference to scarlet fever].

PMID- 15443740
TI  - [Function of the adrenal cortex in acute and chronic diseases of childhood;
      adrenocortical function in various forms of infantile tuberculosis].

PMID- 15443741
TI  - [Investigation of hemoglobin metabolism in premature infants and its significance
      in the pathogenesis of anemia in premature infants].

PMID- 15443742
TI  - [Demonstration of antibodies in the cerebrospinal fluid in tuberculous
      meningitis, with special reference to Meinecke's tuberculosis test].

PMID- 15443743
TI  - [Examination of the epithelial smear in diagnosis of latent vitamin A deficiency
      and threatened keratomalacia in infancy].

PMID- 15443744
TI  - [Complications and untoward results of BCG vaccination].

PMID- 15443746
TI  - [Harmonious analysis of the human precordial electrocardiogram].

PMID- 15443745
TI  - [Franz Volhard, 1872-1950].

PMID- 15443747
TI  - [Cardiac amyloidosis with special reference to electrocardiographic findings].

PMID- 15443748
TI  - [Physiology of the heart].

PMID- 15443749
TI  - [Problem of acute, idiopathic myocarditis].

PMID- 15443750
TI  - [Choice of treatment in chronic disease of the maxillary and frontal sinuses].

PMID- 15443751
TI  - [Effect of streptomycin therapy upon larynx, pharynx, and ear].

PMID- 15443752
TI  - [Differential diagnosis of acoustic neuritis and Meniere's disease].

PMID- 15443753
TI  - [Practical significance of thermoelectric measurements of tube grafts].

PMID- 15443754
TI  - [The amylolytic and glycolytic ferments of the pharyngeal lymphatic ring].

PMID- 15443755
TI  - [Temperature conduction from the external auditory meatus to the vestibular
      apparatus following application of heat].

PMID- 15443756
TI  - [Evaluation of commercial pectins by the method of gel-units].

PMID- 15443757
TI  - [Suggestion for a qualitative analysis of pectins].

PMID- 15443758
TI  - [New dulcigens; use of p-methoxy-o-benzoic acid as a sweetener; determination and
      analysis].

PMID- 15443759
TI  - [Amino acid content of cereals and soybean].

PMID- 15443760
TI  - [A new rapid method for determination of crude fibre].

PMID- 15443761
TI  - [Efficiency of usual methods of potato peeling].

PMID- 15443762
TI  - [Polymer carbohydrates in sauerkraut brine].

PMID- 15443763
TI  - [Variations in extraneous water content of identically prepared sausages;
      critical observations on an article of like title by R. Grau].

PMID- 15443764
TI  - [Reply to Lindner].

PMID- 15443765
TI  - [Demonstration of rye flour in mixed flours and breads using trifructosan].

PMID- 15443766
TI  - [George Hohmann -- 70th birthday].

PMID- 15443767
TI  - [Prof. Richard Scherb -- 70 years].

PMID- 15443768
TI  - [Quantitative determination of pelvic movements in physiological and pathological
      gait].

PMID- 15443769
TI  - [Problem of muscular physiology in orthopedics; injuries of the knee-joint].

PMID- 15443770
TI  - [Orthopedic problem].

PMID- 15443771
TI  - [Treatment of osteochondrosis deformans juvenilis coxae].

PMID- 15443772
TI  - [Dysplasia as causal factor].

PMID- 15443773
TI  - [Calcification of the nucleus pulposus].

PMID- 15443774
TI  - [Antetorsion, retroversion and pathogenesis of dislocation of the hip-joint].

PMID- 15443775
TI  - [Treatment of congenital dislocation of the hip].

PMID- 15443776
TI  - [Treatment of coxa valga luxans].

PMID- 15443777
TI  - [Plastic surgery in substitution of the cruciate ligaments of the knee-joint by
      means of pedunculated tendon transplants].

PMID- 15443778
TI  - [Treatment of poliomyelitis].

PMID- 15443779
TI  - [Treatment of spastic hemiplegia by Stoffel-Silfverskiold's modified operation].

PMID- 15443780
TI  - [Treatment of claw-and-hammer toes by means of an osseous bolt].

PMID- 15443781
TI  - [Operative modification of the femur with a pseudarthrosis in treatment of coxa
      vara congenita].

PMID- 15443782
TI  - [Ischiofemoral extraarticular arthrodesis].

PMID- 15443783
TI  - [Technic in arthrodesis in osteoarticular tuberculosis].

PMID- 15443784
TI  - [New, dependable appliance for nailing of femoral neck and arthrodesis of the
      hip].

PMID- 15443785
TI  - [Arthrodesis of the hip-joint].

PMID- 15443787
TI  - [Technic, indications and prognosis in Smith-Petersen's cup arthroplasty of the
      hip].

PMID- 15443786
TI  - [Experience with vitallium cup arthroplasty of the hip].

PMID- 15443788
TI  - [Boring of the femoral neck in coxarthrosis deformans; results and indications].

PMID- 15443789
TI  - [Operative therapy of arthrosis deformans of the hip].

PMID- 15443790
TI  - [Significance of contrast roentgenography in diagnosis and therapy of subluxation
      of the hip-joint in children].

PMID- 15443791
TI  - [Treatment of idiopathic scoliosis].

PMID- 15443792
TI  - [Treatment of pseudarthrosis of the scaphoid, inner malleolus, and acromion].

PMID- 15443793
TI  - [Extensive surgical experience in support of the theory that muscular anomalies
      are the cause of flatfoot].

PMID- 15443794
TI  - [Anterior tibial muscle in flatfoot and talipes cavus].

PMID- 15443795
TI  - [Pathology of congenital clubfoot; the problem of clubfoot from the point of view
      of pathologic anatomy and histology].

PMID- 15443796
TI  - [Observations on the treatment of congenital clubfoot].

PMID- 15443797
TI  - [Primary treatment of congenital clubfoot; experience with 48 cases of clubfoot
      in infants].

PMID- 15443798
TI  - [Permanent medullary nail for treatment of pseudarthrosis].

PMID- 15443799
TI  - [Multiple epiphyseal disorders as a manifestation of renal rickets].

PMID- 15443800
TI  - [Acute rheumatism during and after the war].

PMID- 15443801
TI  - [Salicylic acid reaction in valvular lesions of the heart].

PMID- 15443802
TI  - [Observations on preceding article].

PMID- 15443803
TI  - [Rheumatism and nervous system; meningeal reactions in rheumatism; the nature of
      meningeal reactions in various forms of rheumatism; the dissociation syndrome].

PMID- 15443804
TI  - [Seminar on rheumatic disease instituted by the Professorial College of the
      Vienna Medical Faculty in cooperation with the Medical Society of Vienna, 2/27
      3/4 1950].

PMID- 15443805
TI  - [Report on the meeting of the German Balneological Society, Inc., 6-7 April 1949,
      in Bad Nenndorf; social balneology].

PMID- 15443806
TI  - [Report on meetings of the German Societies for Pharmacology, Circulatory
      Research, and Internal Medicine, 12-20 April 1950, in Bad Nauheim and Wiesbaden].

PMID- 15443807
TI  - [Initial stages of tuberculosis in diabetics].

PMID- 15443808
TI  - [Pneumoperitoneum].

PMID- 15443809
TI  - [Anatomophysiologic conditions and indications for phrenicectomy and
      pneumoperitoneum].

PMID- 15443810
TI  - [Vitamin D therapy of extrapulmonary tuberculosis].

PMID- 15443811
TI  - [Anal fistula cause by sacrococcygeal tuberculosis].

PMID- 15443812
TI  - [Excerpt from the transactions of the Fifth National Soviet Congress for
      tuberculosis; early forms of tuberculosis].

PMID- 15443813
TI  - [In memoriam Gustav Baer].

PMID- 15443814
TI  - [Congress of the German Urological Society in Munich].

PMID- 15443815
TI  - [Content of phosphatase in the ejaculation during repeated examinations, with and
      without medicamentous treatment in the interval].

PMID- 15443816
TI  - [Diagnosis of renal carbuncle].

PMID- 15443817
TI  - [Progress in diagnosis of renal function: colorimetric micromethod for
      determination of the buffer capacity of the renal pelvic urine during Rehn's
      functional test].

PMID- 15443818
TI  - [Clinical aspects of the amyloid kidney].

PMID- 15443819
TI  - [Sarcoma metastasis in the ureter].

PMID- 15443820
TI  - [Control of bladder tenesmus with humanol].

PMID- 15443821
TI  - [Oversized ureteral calculus with perforation into the bladder].

PMID- 15443822
TI  - [Morphologic studies of hypertrophy of the prostate].

PMID- 15443823
TI  - [Leukoplakia of the renal pelvis resembling a cholesteatoma, and carcinoma of the
      bladder in primary leukoplakia of the bladder and right ureter].

PMID- 15443824
TI  - [Cytologic diagnosis of malignant tumors of the urinary tract].

PMID- 15443825
TI  - [Variations of the prostatic secretion in prostatorrhea].

PMID- 15443826
TI  - [Treatment of disorders of micturition].

PMID- 15443827
TI  - [Renal actinomycosis].

PMID- 15443828
TI  - [Trichomoniasis of the male urethra and prostate].

PMID- 15443829
TI  - [Urinary incontinence].

PMID- 15443830
TI  - [Roentgenologic diagnosis of appendicitis during a urologic examination].

PMID- 15443831
TI  - [Multiple urinary calculi in hypertrophy of the prostate].

PMID- 15443832
TI  - [Bilateral ureterocele with calculus formation].

PMID- 15443833
TI  - [Giant urethral calculus].

PMID- 15443834
TI  - [Primary tumor of the ureter].

PMID- 15443835
TI  - [To O. Kneise on his 75th birthday from his friends and students].

PMID- 15443836
TI  - [Report on 100 retropubic prostatectomies].

PMID- 15443838
TI  - [A few cases of migration of foreign bodies into the bladder].

PMID- 15443837
TI  - [Problem of resection of the renal vessels].

PMID- 15443839
TI  - [Nature of prostatism with special reference to nephrogenous acidosis].

PMID- 15443840
TI  - [Cystectomy in diffuse papillomatosis of the bladder; problem of therapy of
      cancer of the bladder].

PMID- 15443841
TI  - [Unusual case of rupture of the urethra, caused by blunt trauma].

PMID- 15443842
TI  - [Report of experience with cyren A in the treatment of 49 cases of prostatic
      carcinoma].

PMID- 15443843
TI  - [Two cases of exogenous tuberculous infection of the urinary tract (bladder and
      urethra)].

PMID- 15443844
TI  - [Chemotherapy of urogenital tuberculosis].

PMID- 15443845
TI  - [Hydronephrosis with numerous calculi].

PMID- 15443847
TI  - [Pyonephrosis on the left, renal calculus on the right].

PMID- 15443846
TI  - [Thorotrast residue].

PMID- 15443848
TI  - [Unusual benign tumor of the tunica vaginalis].

PMID- 15443849
TI  - [Lymphogranulomatosis of the upper digestive tract].

PMID- 15443850
TI  - [Observations on malacoplakia of the bladder and kidney pelvis].

PMID- 15443851
TI  - [Anatomicopathological modifications following infection with the enterotoxic
      bacillus (Zeissler) in animal experimentation; appearance of gaseous edema
      following intramuscular infection of guinea-pigs and on the origin of the
      pathogenic factor of gaseous edema in man].

PMID- 15443852
TI  - [Periinfundibular densification ring in suppurative basilar meningitis].

PMID- 15443854
TI  - [Polymorphocellular leiomyosarcoma of the prostate in a boy, 3 years of age].

PMID- 15443853
TI  - [Circular aortic rupture and simulated aneurysm in suppurative aortitis].

PMID- 15443855
TI  - [Combination of lymphogranulomatosis, tuberculosis and malignant tumors of the
      lungs and lymph nodes].

PMID- 15443857
TI  - [Generalized calcinosis].

PMID- 15443856
TI  - [Fatal hemorrhage from bladder varices].

PMID- 15443858
TI  - [Complicated malformation of the lower trunk].

PMID- 15443859
TI  - [Unusually large liver cells in equine liver dystrophy (Schweinberger disease)].

PMID- 15443860
TI  - [Malignancy of dermoid cysts and teratomata].

PMID- 15443861
TI  - [Benign bronchial adenoma (carcinoid) with multiple recurrence after ten years].

PMID- 15443862
TI  - [Flora of the cadaveric stomach].

PMID- 15443863
TI  - [Jejunogastric invagination following gastroenterostomy].

PMID- 15443864
TI  - [Miniature- and micro-carcinoma of the bronchi].

PMID- 15443865
TI  - [Arthur Meiner on his 85th birthday].

PMID- 15443866
TI  - [Clinical and histological observations on sterility].

PMID- 15443867
TI  - [Preoperative radiotherapy of uterine cancer].

PMID- 15443869
TI  - [Myolipofibroma of the uterus; case report].

PMID- 15443868
TI  - [Roentgen castration in climacteric hemorrhage].

PMID- 15443870
TI  - [Critical observations on intrauterine sulfonamide therapy].

PMID- 15443871
TI  - [Experimental and clinical investigations on the estrogenic effect of ichth
      oestron].

PMID- 15443872
TI  - [Treatment of secondary amenorrhea with cyren-A-tardum crystals].

PMID- 15443873
TI  - [Late results of androgen therapy].

PMID- 15443874
TI  - [Effect of vitamin C on iron resorption].

PMID- 15443875
TI  - [Michurin's selection of fruit and berry varieties in the Ukraine for seedling
      purposes].

PMID- 15443876
TI  - [Biologic aspect of the development of hybrid seedlings of the apple tree].

PMID- 15443877
TI  - [Biologic aspects of artificial insemination of domestic animals].

PMID- 15443878
TI  - [Deep refrigeration of the semen of domestic animals].

PMID- 15443879
TI  - [Decisive role of outer media and functional state of the organism in ontogenesis
      of the blood plasma in horses].

PMID- 15443880
TI  - [Objective method in the study of the behavior of insects (silkworm)].

PMID- 15443881
TI  - [Further data on vegetative heredity in modified forms of the animal organism].

PMID- 15443882
TI  - [Criticism of Malthusianism by I. I. Mechnikov].

PMID- 15443883
TI  - [Progress of Pavlov's physiology].

PMID- 15443884
TI  - [Certain principles in the theory of regeneration].

PMID- 15443885
TI  - [Biological aging of the tomato plant in vegetative reproduction].

PMID- 15443886
TI  - [Study of the process of nectar secretion].

PMID- 15443887
TI  - [Sixth meeting on parasitological problems in the Zoological Institute of the
      Academy of Science].

PMID- 15443888
TI  - [Effect of agricultural methods on the population of the tick Hyalomma marginatum
      Koch. in field protecting forested regions].

PMID- 15443889
TI  - [Destructive turtle Eurygaster integriceps Put. in forrested agricultural
      regions].

PMID- 15443890
TI  - [Organic integration of colonial hydroidea; experiments with Obelia longissima
      and Laeomedea flexuosa].

PMID- 15443891
TI  - [Propagation of ligula in Estonian waters].

PMID- 15443892
TI  - [Characteristics of embryonic development of Asiatic locust (Locusta migratoria
      L.) in relation to certain environment].

PMID- 15443893
TI  - [Importance of humidity of environment and food in cold resistance of Calandra
      granaria L..].

PMID- 15443894
TI  - [Cranial biomechanics].

PMID- 15443895
TI  - [Cave fauna of Western Trans-Caucasia].

PMID- 15443896
TI  - [Methods of costal hydrobiological studies].

PMID- 15443897
TI  - [Study of the propagation of the spotted scorpion (Buthus eupeus Koch.)].

PMID- 15443898
TI  - The 'body scheme' in psychotherapy.

PMID- 15443899
TI  - [Late treatment of dislocated healed fractures of the maxilla].

PMID- 15443900
TI  - Crystalline alcohol dehydrogenase from baker's yeast.

PMID- 15443901
TI  - [Structural modifications of the skeletal muscles of infants having died from
      dystrophy, atrophy, nutritional intoxication].

PMID- 15443902
TI  - Hysterography in cancer of the corpus of the uterus.

PMID- 15443903
TI  - [Diagnosis of hamartoma of the liver].

PMID- 15443904
TI  - [Modifications of the thyroid in chronic malnutrition and hunger].

PMID- 15443905
TI  - [On the sinal nodes of anthropoid apes].

PMID- 15443906
TI  - [Histological investigation of the effect of experimental oxygen deficiency on
      the cat heart].

PMID- 15443907
TI  - [Modifications of the human brain in chronic and acute general oxygen
      deficiency].

PMID- 15443908
TI  - [Pathogenesis of thromboendarteritis obliterans (v. Winiwarter-Buerger) of
      cerebral vessels, and the problem of rheumatic injuries of the brain].

PMID- 15443909
TI  - [Coronary sclerosis in hypertension].

PMID- 15443910
TI  - [Experimental perfusion of the coronary system with normal, hypertrophic and
      atrophic heart muscle].

PMID- 15443911
TI  - [Tissue injuries due to thorotrast with special reference to vascular
      modifications and aplastic bone marrow reactions].

PMID- 15443912
TI  - [Late development of a carcinoma of the lower eyelid, following thorium dioxide
      injection].

PMID- 15443913
TI  - [The cranium, history and self-observation of a soldier with a maxillo-facial
      wound from the Battle of Jena, 1806].

PMID- 15443914
TI  - [Fibrous osteopathy; hyperplastic tumors and latent sclerosis of the jaws].

PMID- 15443915
TI  - [Preparation of onlays for upper incisors used as bridge support].

PMID- 15443916
TI  - [Case of neuralgia of the inferior dental nerve treated by neurotomy above Spix's
      spine].

PMID- 15443917
TI  - [Giant epulis].

PMID- 15443918
TI  - [A pseudo-tumoral form of osteitis of the mandible in a 7 year old girl;
      spontaneous cure].

PMID- 15443919
TI  - [Stomatologic considerations of a severe case of hemogenia].

PMID- 15443920
TI  - [Treatment of a cyst of the mandible with trichloroacetic acid].

PMID- 15443921
TI  - [Cystic adamantinoma of the mandible; histologic examination].

PMID- 15443922
TI  - [Preparation of onlay for upper incisor used as bridge support].

PMID- 15443923
TI  - [Calcification of pulp].

PMID- 15443924
TI  - [Dentition of the earliest mammals].

PMID- 15443925
TI  - [Case of a grave form of recurrent adamantinoma of the mandible treated by
      trichloroacetic acid and, at present, clinically and radiologically cured].

PMID- 15443926
TI  - [Case of incisor gap treated by surgical lowering of the upper incisor-canine
      mass].

PMID- 15443927
TI  - [Case of fibroma of the gingiva].

PMID- 15443928
TI  - [Case of dyskeratosic glossitis].

PMID- 15443929
TI  - [Case of fibrous osteitis of the mandible].

PMID- 15443930
TI  - [Case of adamantinoma].

PMID- 15443931
TI  - [Resection of the upper frenum labiorum; indications; technic].

PMID- 15443932
TI  - [Not Available].

PMID- 15443933
TI  - [Scleroderma of the upper lip].

PMID- 15443934
TI  - [Classification of chronic pulpitis].

PMID- 15443935
TI  - [Do fibrils of Tomes exist in dentin?].

PMID- 15443936
TI  - [Regarding the article by Grether on dens in dente].

PMID- 15443937
TI  - [Supernumerary wisdom teeth].

PMID- 15443938
TI  - [Planispheric radiography in stomatology].

PMID- 15443939
TI  - [Importance of simultaneous tomography in stomatology].

PMID- 15443940
TI  - [Buccodental survey of the tribes of the Pool district, French Equatorial
      Africa].

PMID- 15443941
TI  - [Dentigerous cyst of the mandible with serious bone destruction].

PMID- 15443942
TI  - [Human saliva: physical properties; chemical composition; cytology; bacteriology;
      serological properties; role].

PMID- 15443944
TI  - [New apparatus for the nailing of fractures of the edentulous mandible].

PMID- 15443943
TI  - [Reactive stomatitis and glossitis].

PMID- 15443946
TI  - [Ptyalism in pregnancy].

PMID- 15443947
TI  - [Mandibular metastasis of an epithelioma of the breast].

PMID- 15443948
TI  - [Simple unilateral harelip operation, modification of the deep muscular
      approximation].

PMID- 15443945
TI  - [Case of facial paralysis of dental origin].

PMID- 15443949
TI  - [Assistance to abandoned children in Portugal].

PMID- 15443950
TI  - [Diphtheria in rural areas. I. Epidemic outbreak in a village].

PMID- 15443951
TI  - [Case of fibroma of vulva].

PMID- 15443952
TI  - [Note on the value of a national committee on hygiene (and eventually of regional
      committees on hygiene)].

PMID- 15443953
TI  - [Study on the epidemiology of poliomyelitis in Ille-et-Vilaine since 1946].

PMID- 15443954
TI  - [The repercussions on the human body of the agricultural use of plant hormones].

PMID- 15443955
TI  - [Procedure of declaring a house insanitary and forbidding habitation: article
      12].

PMID- 15443956
TI  - [Evolution of diphtheria in Avignon].

PMID- 15443957
TI  - [Hygienic measures concerning the sale of beer].

PMID- 15443958
TI  - Genetics of convergent strabismus.

PMID- 15443959
TI  - Mental deficiency.

PMID- 15443960
TI  - Observations of hereditary somatic diseases in Finland and their importance in
      the medical marriage guidance.

PMID- 15443961
TI  - A note on drinking and drunkards in Sweden.

PMID- 15443962
TI  - Chronic rheumatic arthritis and housing conditions.

PMID- 15443963
TI  - [Caries, pregnancy and lactation].

PMID- 15443964
TI  - Odontogenic cysts and cystic tumours of the jaws. A roentgen-diagnostic and patho
      anatomic study.

PMID- 15443965
TI  - [Control procedures applied to apparatus and products for continuous or permanent
      disinfection].

PMID- 15443966
TI  - [Control of mosquitoes on the airfields of Orly and Bourget].

PMID- 15443967
TI  - [Results of the helio-seaside treatment at the Preventorium for Children at Saint
      Laurent in Plerin].

PMID- 15443968
TI  - [Indications and contraindications of sialography].

PMID- 15443969
TI  - [Sialographic technic].

PMID- 15443970
TI  - [Sialographic technic].

PMID- 15443972
TI  - [Discussion on sialographic technic].

PMID- 15443971
TI  - [A sialographic technic].

PMID- 15443973
TI  - [Sialographic technic].

PMID- 15443974
TI  - [Difficulties and complications in the course of sialography].

PMID- 15443975
TI  - [X-ray of normal parotid glands].

PMID- 15443976
TI  - [Acute parotitis].

PMID- 15443977
TI  - [Chronic parotitis].

PMID- 15443978
TI  - [Tumors].

PMID- 15443979
TI  - [Sialography of parotid tumors].

PMID- 15443980
TI  - [Comment on the meeting].

PMID- 15443981
TI  - The physiological importance of the casein phosphopeptide calcium salts. I.
      Intravenous and peroral calcium cosage in animal experiments.

PMID- 15443982
TI  - The physiological importance of the casein phosphopeptide calcium salts. II.
      Peroral calcium dosage of infants.

PMID- 15443983
TI  - Thresher's lung; (pulmonary moniliasis). An experimental investigation.

PMID- 15443984
TI  - Operative treatment of thyrotoxicosis following thyroid medication.

PMID- 15443985
TI  - Conduction anaesthesia in obstetrics; caudal anaesthesia, lumbar peridural
      anaesthesia and bilateral lumbar sympathetic block with single doses of xylocaine
      in 231 deliveries.

PMID- 15443986
TI  - [Not Available].

PMID- 15443987
TI  - [Notes on the International Tuberculosis Congress at Copenhagen, September 1950].

PMID- 15443988
TI  - [Compulsory declaration, a major element in control of tuberculosis].

PMID- 15443989
TI  - [The relationship between disinfectant power and destruction by heat].

PMID- 15443990
TI  - [Remarks on some aspects of housing hygiene in France].

PMID- 15443991
TI  - [Pollution of the atmosphere in the region of Rouen].

PMID- 15443992
TI  - [Not Available].

PMID- 15443993
TI  - [Associated penicillin-chloromycetin therapy of a circumscribed gangrenous
      sublingual phlegmon of dental origin].

PMID- 15443994
TI  - [Spread of bacteria during dental surgery].

PMID- 15443995
TI  - [Histological study of a central incisor in an osteomyelitic mandible].

PMID- 15443996
TI  - [Acrylic resins in the lower jaw of the dog].

PMID- 15443997
TI  - [The molarization of premolars in mammals].

PMID- 15443998
TI  - [Hypertrophy of the jaws in facial angiomas].

PMID- 15443999
TI  - [Facial neuralgia with characteristics of tic douloureux in a patient with an
      impacted lower right canine].

PMID- 15444000
TI  - [The vertico-frontal plane of the head; the constant of its geometric relations
      with the horizontal vestibular plane; superiority in clinical examination].

PMID- 15444001
TI  - [Experimental study of the role of the epithelium in development of the teeth].

PMID- 15444002
TI  - [Central circumpulpal dentine].

PMID- 15444003
TI  - [Prophylaxis of dental caries with ammonium].

PMID- 15444004
TI  - [Removable artificial gingiva].

PMID- 15444005
TI  - [Solidarization in the mouth of splints by means of autopolymerizing resins].

PMID- 15444006
TI  - [A case of tuberculo-ulcerous syphilids on the lips].

PMID- 15444007
TI  - [2 Cases of infraclusion in the molar region].

PMID- 15444008
TI  - [Growth of the face in utero].

PMID- 15444009
TI  - The frequency of mumps and of mumps orchitis and the consequences for sexuality
      and fertility.

PMID- 15444010
TI  - Gustaf F. Gothlin.

PMID- 15444011
TI  - Studies on the iron in the yolk sac of the pregnant rat in normal and anemic
      conditions.

PMID- 15444012
TI  - Experiments on the effect of batyl alcohol on the number of erythrocytes and
      reticulocytes in white mice.

PMID- 15444013
TI  - A simple method to separate lymphocytes from the blood.

PMID- 15444014
TI  - The resistance of white blood corpuscles in autologous and homologous human sera.

PMID- 15444015
TI  - A case of mesothelioma of the pleura and peritoneum producing hyaluronic acid.

PMID- 15444016
TI  - Hyaluronic acid in the pleural and peritoneal fluids from a case of mesothelioma.

PMID- 15444017
TI  - Encephalomyocarditis acuta--a disease sui generis?

PMID- 15444018
TI  - Occurrence and distribution of fat in human muscles at various age levels; a
      morphologic and roentgenologic investigation.

PMID- 15444019
TI  - [Heredity and dento-maxillary abnormalities].

PMID- 15444020
TI  - [Omega-diethylamino-2-6-dimethylacetanilide (xylocaine) effect on the suppression
      of adrenaline in local anesthesia].

PMID- 15444021
TI  - [Correlation of different parts of the facial skeleton].

PMID- 15444022
TI  - [Osteoma of the mandibular angle aggravated by radiotherapy].

PMID- 15444023
TI  - [Partial dental dislocations due to chronic trauma].

PMID- 15444024
TI  - [Plastic surgery of the oral vestibule].

PMID- 15444025
TI  - [Note on bacteriology of osteophlegmons and adenophlegmons in children].

PMID- 15444026
TI  - [Secondary mandibular cancer].

PMID- 15444027
TI  - [Lateral mandibular dislocation].

PMID- 15444028
TI  - [Incidence in Vietnam of coexistence of deciduous & permanent teeth].

PMID- 15444029
TI  - [Not Available].

PMID- 15444030
TI  - Soft tissue radiography; technical aspects and clinical applications in the
      examination of limbs.

PMID- 15444031
TI  - Roentgen examination of pleural fluid; a study of the localization of free
      effusions, the potentialities of diagnosing minimal quantities of fluid and its
      existence under physiological conditions.

PMID- 15444033
TI  - [Studies on chromosome markings in a family with dominant retinitis pigmentosa].

PMID- 15444032
TI  - An enzymatic study on the structure of yeast ribose nucleic acid.

PMID- 15444034
TI  - The formal logic of the nature-nurture issue.

PMID- 15444035
TI  - Mortality in Norwegian mental hospitals 1926-1941.

PMID- 15444036
TI  - A note on the relative death rate.

PMID- 15444037
TI  - A note on the thrombocytes in hemophilics.

PMID- 15444038
TI  - Seasonal birth frequencies in parameters.

PMID- 15444039
TI  - [For what price can people of Marseille drink a truly potable water?].

PMID- 15444040
TI  - [Study on the comparative value of certain foods in animal growth].

PMID- 15444041
TI  - [Bovine brucellosis and the milk supply of cities].

PMID- 15444042
TI  - [Periodic pollution of rivers by industrial distillation residues].

PMID- 15444043
TI  - [Dietary deficiencies; trace elements].

PMID- 15444044
TI  - Studies on the hepatic ducts in cholangiography.

PMID- 15444045
TI  - Vertebral angiography by catheterization; a new method employed in 221 cases.

PMID- 15444046
TI  - Transit time through the small intestine, a roentgenologic study on normal
      variability.

PMID- 15444047
TI  - [Contributions to the anatomy and diseases associated with human constitution].

PMID- 15444048
TI  - [Modification of gill development in the triton in experimental anoxemia, and a
      contribution to the problem of functional hyperplasia].

PMID- 15444049
TI  - [Phosphatide regeneration in liver and kidneys of the rat during respiration
      under partial oxygen pressure; investigations with radiophosphorus].

PMID- 15444050
TI  - [Brown lipoma and brown fatty tissue in man].

PMID- 15444051
TI  - [Encephalomyelitis in toxoplasma infection].

PMID- 15444052
TI  - [Histological and chemical studies of osteolysis in experimental fractures and
      transplants].

PMID- 15444053
TI  - [Structural pancreatic changes in so-called cystic pancreas fibrosis].

PMID- 15444054
TI  - [Relations between the therapeutic effects of TB I/698 and the retothelial cell
      system in experimental tuberculosis].

PMID- 15444055
TI  - [Morphological findings in chemotherapy of fatal tuberculosis].

PMID- 15444056
TI  - [Ganglioneuroblastoma as hereditary disease of the sympathetic nervous system].

PMID- 15444057
TI  - [On the question of neurosecretion of sympathetic ganglia after examination of
      the human and animal stellate ganglion].

PMID- 15444058
TI  - [Histological examination of the diencephalon in hypertension].

PMID- 15444059
TI  - [Meningioma and their variable effects on the brain].

PMID- 15444060
TI  - [On hypertrophic neuritis (Roussy-Cornil)].

PMID- 15444061
TI  - [Fatal adult case of toxoplasmosis].

PMID- 15444062
TI  - [Contribution to morphological pathology of monocytic leukemia].

PMID- 15444063
TI  - [Pathogenesis of Von Gierke's disease].

PMID- 15444064
TI  - [Experimental-morphological study of effect of ultrasonic waves on skin,
      musculature, heart and lungs in the rabbit].

PMID- 15444065
TI  - Biochemical gradients in the axolotl gastrula.

PMID- 15444066
TI  - Sorption of water vapor by plakalbumin.

PMID- 15444067
TI  - [Buccodental signs of diabetes in children].

PMID- 15444068
TI  - [Reflections on several cases of paradentosis observed in Tonkin].

PMID- 15444069
TI  - [Followup on surgery for cystic adamantinoma of the mandible].

PMID- 15444070
TI  - [Contribution to the study of the in utero growth of the mandible].

PMID- 15444071
TI  - [Introduction to biological orthodontics; study of the growth of the face].

PMID- 15444072
TI  - [Anatomical study of the inferior dental artery in the fetus and adult].

PMID- 15444073
TI  - [Cysts of jaws with vital teeth].

PMID- 15444074
TI  - [Recent data in dental histology].

PMID- 15444075
TI  - [A new apparatus for histologic technique].

PMID- 15444077
TI  - [Dystrophy of local etiology].

PMID- 15444076
TI  - [Coronary dentoma or osteoma? Removal with conservation of the tooth].

PMID- 15444078
TI  - [Morphological abnormality from trauma].

PMID- 15444079
TI  - [Irritative lesions of the palate provoked by pipe tobacco].

PMID- 15444080
TI  - [Granular gingiva].

PMID- 15444081
TI  - [Helminthic stomatitis].

PMID- 15444082
TI  - [A case of Rose's kopf-tetanus].

PMID- 15444083
TI  - [Traumatic hydrarthrosis or hemarthrosis of the temporomandibular joint with
      homolateral molar gap].

PMID- 15444084
TI  - [Mixed submucosal tumor of the cheek].

PMID- 15444085
TI  - [Dental dystrophy of probable typhoid origin].

PMID- 15444086
TI  - [Displacement of the maxilla by a transsinusal osteotomy].

PMID- 15444087
TI  - [Case of grave acute osteomyelitis of dental origin treated and cured without
      sequestration by combined penicillin and streptomycin].

PMID- 15444088
TI  - [Trial tissue therapy in pyorrhea].

PMID- 15444089
TI  - [Double osteotom~ of the mandible for prognathism (Kostecka method);
      considerations on the displacement of the fragments after osteotomy of the
      ascending processes].

PMID- 15444090
TI  - [Note on R. Bataille's article on Secondary cancer of the mandible].

PMID- 15444091
TI  - [Chronic parotitis].

PMID- 15444092
TI  - [Treatment of pyorrhea].

PMID- 15444093
TI  - [Hemostasis in stomatology].

PMID- 15444094
TI  - [Bucco-sinusal communications; surgical treatment].

PMID- 15444096
TI  - [Osteites of the malar bone].

PMID- 15444095
TI  - [Cementoblastoma, cementoma].

PMID- 15444097
TI  - [Cephalic localizations of neurofibromatosis].

PMID- 15444098
TI  - [Not Available].

PMID- 15444099
TI  - [Unusual foreign body of the esophagus, fragment of plaster swallowed during
      taking of a dental impression].

PMID- 15444100
TI  - [Orthodontic record card].

PMID- 15444101
TI  - [Aplasia of the left ascending ramus of the mandible (2nd presentation). Graft of
      iliac bone by Dr. Ginestet. Anatomic, clinical and radiologic results after three
      years].

PMID- 15444102
TI  - [Gingival hemoculture in pyorrhea (comparative study of cultures in aerobic and
      anaerobic media)].

PMID- 15444103
TI  - [Subacute spontaneously curable cervicofacial adenopathy. Inoculation
      lymphoreticulosis].

PMID- 15444104
TI  - [Splints for jaw fractures and autopolymerizing resins].

PMID- 15444105
TI  - [Three cases of benign tumors of the maxilla].

PMID- 15444106
TI  - [A case of chloroma].

PMID- 15444107
TI  - [Unoxidizable alloys; physical, chemical and mechanical study; prosthetic
      applications].

PMID- 15444108
TI  - [Multiple cancers of the oral cavity].

PMID- 15444109
TI  - [Hydrocolloid technic for fixed prostheses].

PMID- 15444110
TI  - [Three cases of multiple impacted teeth disclosing cleidocranial dystosis].

PMID- 15444111
TI  - [Eosinophilic granuloma of the jaws].

PMID- 15444112
TI  - [Postnatal mandibular development; exact details on the chronology of the
      symphysis].

PMID- 15444113
TI  - [A voluminous submental adenitis provoked by a mandibular wisdom tooth].

PMID- 15444114
TI  - [Presentation of a case of oral tumor with a difficult diagnosis].

PMID- 15444115
TI  - [Osteitis of the border of the mandibular notch].

PMID- 15444116
TI  - [Giant periodontal cyst of the mandible operated on by a mixed method].

PMID- 15444117
TI  - [A new line of reference for the analysis of sagittal teleradiographs in
      orthodontia].

PMID- 15444118
TI  - [Replacement of facing of a tooth by means of screws].

PMID- 15444119
TI  - [The temporary dentition, called the milk teeth, of man and anthropoid apes].

PMID- 15444120
TI  - [Vast reconstruction of the cheek and maxilla after radionecrosis of the bone].

PMID- 15444121
TI  - [Comments on a full upper removable bridge worn for thirty years].

PMID- 15444122
TI  - [Painful syndrome of the face causing a glossopharyngeal neuralgia, having
      disappeared for six months after infiltrations of the carotid bifurcation].

PMID- 15444124
TI  - [Some comments on the use of penicillin in stomatology].

PMID- 15444123
TI  - [Septicopyemia in diabetic following staphylococcic cheilitis].

PMID- 15444125
TI  - [Plastic surgery of the lingual aspect of the alveolar crest of the mandible;
      contribution to the solution of the problem of the lower prosthesis].

PMID- 15444126
TI  - [Pathologic development of dental enamel and free tumors of enamel tissue].

PMID- 15444127
TI  - [Improvements in the use of hydrocolloids for fixed prostheses].

PMID- 15444128
TI  - [Articulator for the preoperative study of lateral deviations of the mandible].

PMID- 15444129
TI  - [Cleido-crania dysostosis with multiple impacted teeth].

PMID- 15444130
TI  - [Untreated traumatic separation of cranial and facial bones; correction of the
      attendant malocclusion by unilateral resection of the condyla of the mandible].

PMID- 15444131
TI  - [A case of Plummer-Vinson syndrome].

PMID- 15444132
TI  - [Value of certain radiographic examinations in the diagnosis of periodontal cysts
      evolving into the sinuses].

PMID- 15444133
TI  - [Not Available].

PMID- 15444134
TI  - [The effect of trauma on the growth of the dental pulp].

PMID- 15444135
TI  - [Biochemical studies on dental caries].

PMID- 15444136
TI  - [Value and indication of fixed and removable orthodontic appliances].

PMID- 15444137
TI  - [Atypical development of mandibular osteomyelitis treated with antibiotics].

PMID- 15444138
TI  - [Clinical and roentgenologic course of mandibular osteitis after antibiotic
      therapy].

PMID- 15444139
TI  - [Pseudoneoplastic forms of mandibular osteitis in children].

PMID- 15444140
TI  - [Oral manifestation of terramycin intolerance].

PMID- 15444141
TI  - [Two cases of sensitization to novocaine].

PMID- 15444142
TI  - [Capdepont disease; hereditary disease following the dominant rules].

PMID- 15444143
TI  - [Histology of the dentin].

PMID- 15444144
TI  - [Frugivorous bats belonging to the oldest mammals].

PMID- 15444145
TI  - [Not Available].

PMID- 15444146
TI  - [Comparative cranio-facial anatomy of mammalia and men].

PMID- 15444147
TI  - [Studies on toothbrushes from nylon].

PMID- 15444148
TI  - [Generalization of cementoma; camentosis].

PMID- 15444149
TI  - [Not Available].

PMID- 15444150
TI  - [Anesthesia in tracheotomy].

PMID- 15444151
TI  - [Clinical results of two years practice with controlled respiration with the
      pulmotor].

PMID- 15444152
TI  - [Standardization of medical gas cylinders and anesthesia equipment].

PMID- 15444153
TI  - [Fall of the rate of oxygen in semi-closed circuits critical study of the
      phenomenon].

PMID- 15444154
TI  - [Bad temper of the surgeon].

PMID- 15444155
TI  - [Critical study of methods in infantile anesthesia].

PMID- 15444156
TI  - [Observations on the problem of warming of the soda lime filter in closed circuit
      anesthesia].

PMID- 15444157
TI  - [Post-transfusional jaundice; six cases with two fatalities].

PMID- 15444158
TI  - [Problems of anesthesia and resuscitation in surgery of traumatism].

PMID- 15444159
TI  - [Treatment of the agonal phase of shock by intra-arterial transfusion].

PMID- 15444160
TI  - [Modifications of eyeball tension due to narcosis, curare and ganglioplegics].

PMID- 15444161
TI  - [Organization of the anesthesia service of the Hopital Tenon].

PMID- 15444162
TI  - [Note on anesthesia of rabbits; use of trichloroethylene].

PMID- 15444163
TI  - [Electric anesthesia, shock and euthanasia without muscular contractions].

PMID- 15444164
TI  - [Control of absorption and distribution of carbon dioxide in apparatus].

PMID- 15444165
TI  - [Some experimental aspects of artificial hibernation].

PMID- 15444166
TI  - [Artificial hibernation; new useful data].

PMID- 15444167
TI  - [Potentialized anesthesia in thoracic surgery].

PMID- 15444168
TI  - [Different degrees of artificial hibernation].

PMID- 15444169
TI  - [Postoperative hypodermoclysis with hyaluronidase].

PMID- 15444170
TI  - [Association of heparin and hyaluronidase].

PMID- 15444171
TI  - [Study of the inhibitor effect of antihistaminics, ganglioplegics and local
      anesthetics on hyaluronidase].

PMID- 15444172
TI  - [Total parenteral feeding for 34 days].

PMID- 15444173
TI  - [Artificial hibernation in anesthesiology].

PMID- 15444174
TI  - Some problems of acid-base equilibrium during anesthesia with particular
      reference to thoracic surgery.

PMID- 15444175
TI  - [Significance and technic of continuous measurement of oxygen saturation of blood
      during narcosis].

PMID- 15444176
TI  - [Mechanism of inhibition of neuromuscular transmission].

PMID- 15444177
TI  - Anaesthetic deaths with special reference to death due to regurgitation and
      vomiting.

PMID- 15444178
TI  - [Contribution to the control of mosquitoes in Alsace; plan for draining swamps
      and reclaiming the land].

PMID- 15444179
TI  - [A plea for splints].

PMID- 15444180
TI  - [A case of Ewing's tumor of the mandible].

PMID- 15444181
TI  - [Stomatologic contributions to the prophylaxis of infectious endocarditis].

PMID- 15444182
TI  - [Antimalarial phytotherapy].

PMID- 15444183
TI  - [The problem of immunity in malaria].

PMID- 15444184
TI  - [Pathogenesis and treatment of tropical phagedenic ulcer].

PMID- 15444185
TI  - [A simple treatment of tropical phagedenic ulcer].

PMID- 15444186
TI  - [Certification in medical parasitology].

PMID- 15444187
TI  - [Not Available].

PMID- 15444188
TI  - [Chronic parotitis].

PMID- 15444189
TI  - [Inflammation of the sub-maxillary glands without calculi].

PMID- 15444190
TI  - [Not Available].

PMID- 15444191
TI  - [Therapy of cervico-facial actinomycosis].

PMID- 15444192
TI  - [Tetanus and wisdom tooth].

PMID- 15444193
TI  - [Bullet enclosed in the pterygo-maxillary region].

PMID- 15444194
TI  - [Iodinated sulfones].

PMID- 15444195
TI  - [Position of deciduous teeth during dentition].

PMID- 15444196
TI  - [Abolition of wiring in therapy of fractures of the mandible].

PMID- 15444197
TI  - [Therapy of pyorrhea alveolaris].

PMID- 15444198
TI  - [Severe periodontal and maxillary lesions caused by permanent handling of
      trinitrotoluol (T.N.T.)].

PMID- 15444199
TI  - [Experimental studies of the toxic effect of beryllium carbonate on the teeth].

PMID- 15444200
TI  - [A simple method to eliminate gingival pockets].

PMID- 15444201
TI  - [Therapy of malignant tumors of the tonsils by radium prosthesis].

PMID- 15444202
TI  - [Alveolar cysts in child].

PMID- 15444203
TI  - [Particularities of the course of the facial nerve and the internal maxillary
      artery in relation to surgery of the temporomandibular joint].

PMID- 15444204
TI  - [Extraction of the palatally impacted cuspid tooth.  Personal method].

PMID- 15444205
TI  - [Advantages of osteosynthesis in the therapy of fractures of the mandible with a
      toothless posterior fragment].

PMID- 15444206
TI  - [Nutritional medicine and dental hygiene].

PMID- 15444207
TI  - [Incidents and accidents in neurolytic injections in trigeminal neuralgia].

PMID- 15444208
TI  - [Blood cultures in gingival diseases].

PMID- 15444209
TI  - [Complementary study on pyorrhea therapy].

PMID- 15444210
TI  - [Control of bleeding in dentistry].

PMID- 15444211
TI  - [Plastic surgery of the soft tissue and of the maxillary bone].

PMID- 15444212
TI  - [Diagnosis, prognosis and therapy of benign and malign tumors of the jaws and
      face].

PMID- 15444213
TI  - [Trigeminal neuralgia and dentistry].

PMID- 15444214
TI  - [Maxillofacial surgery in North-America].

PMID- 15444215
TI  - [Some cases of actinomycosis].

PMID- 15444216
TI  - [Role of absence of granulocytes in buccal lesions of acute leucemia].

PMID- 15444217
TI  - [Surgery of large cysts of the jaws].

PMID- 15444218
TI  - [Prefabricated rings with folded top].

PMID- 15444219
TI  - [Soldering in low temperature for orthodontics].

PMID- 15444220
TI  - [Falkon beak shaped forceps for upper molars].

PMID- 15444221
TI  - [Diagnosis and therapy of endognathy].

PMID- 15444222
TI  - [A new technic in therapy of maxillary expansion].

PMID- 15444223
TI  - [The value of various filling materials with special reference to acrylic
      resins].

PMID- 15444224
TI  - [Orthodontia and endocrinology].

PMID- 15444225
TI  - [Communications between the mouth and sinuses].

PMID- 15444226
TI  - [The speech center of Amsterdam, surgery, prosthetics, orthodontics and phonetics
      of the cleft palate].

PMID- 15444227
TI  - [Estlander-Abbe method in therapy of secondary deformations of the harelip].

PMID- 15444228
TI  - [Surgery in loss of substance of the roof of the mouth].

PMID- 15444229
TI  - [Adamantinoma of the jaws and their surgery].

PMID- 15444230
TI  - [Conservative therapy of adamantinoma of the jaws].

PMID- 15444231
TI  - [Systematic prevention of accidents in tooth extractions; intervention in two
      sessions].

PMID- 15444232
TI  - [Crowns with acrylic facing].

PMID- 15444234
TI  - [Tumor of the jaws in small children].

PMID- 15444233
TI  - [Arterenol as vaso-constrictor in local anesthesia].

PMID- 15444235
TI  - [Hydrocolloids in every days use].

PMID- 15444236
TI  - [A new link for partial free-end prosthesis].

PMID- 15444237
TI  - [Radiopantomography].

PMID- 15444238
TI  - [Not Available].

PMID- 15444239
TI  - [The fundamental type of mammalian molars and its evolution].

PMID- 15444240
TI  - [Cyst of the mandible treated by a bone graft].

PMID- 15444241
TI  - [A case of primary lupus of the gingiva].

PMID- 15444242
TI  - [Four cases of latent congenital cysts of the neck; diagnosis of cytological
      examination].

PMID- 15444243
TI  - [Periodontal diseases and neurovascular disturbances; experimental study].

PMID- 15444244
TI  - [A case of eczema of the lips and the oral mucosa; some considerations on eczema
      of the oral mucosa].

PMID- 15444245
TI  - [Medical progress in Slovakia].

PMID- 15444246
TI  - [Health education in USSR].

PMID- 15444247
TI  - [Public health in USSR and in Czechoslovakia].

PMID- 15444248
TI  - [Neuroses according to the Pavlovian theory].

PMID- 15444249
TI  - [Treatment of myocarditis in children].

PMID- 15444250
TI  - [Considerations on salpigography and pertubation].

PMID- 15444251
TI  - [Surgical treatment of lumboischiatic syndrome].

PMID- 15444252
TI  - [Symptoms in retropharyngeal abscess in infants].

PMID- 15444253
TI  - [First aid in fractures of the jaws].

PMID- 15444254
TI  - [Organization of public health in USSR].

PMID- 15444255
TI  - [Theory and practice in medicine].

PMID- 15444256
TI  - [Development of medical science in Rumanian Peoples Republic].

PMID- 15444257
TI  - [Hygiene in mining].

PMID- 15444258
TI  - [Qualititative analysis of health services in mines].

PMID- 15444259
TI  - [Control of tuberculosis in industry].

PMID- 15444260
TI  - [Problem of rheumatism in miners].

PMID- 15444261
TI  - [Control of rheumatism in miners and rehabilitation].

PMID- 15444262
TI  - [Injuries of the eye in building industry].

PMID- 15444263
TI  - [Penicillin in obstetrics and gynecology].

PMID- 15444265
TI  - [In memory of Milan Polak].

PMID- 15444264
TI  - [Significance of the spleen in hemopoiesis].

PMID- 15444266
TI  - [Hygiene according to the Pavlovian theory].

PMID- 15444267
TI  - [Organization of the control of typhoid fever in Greater Bratislava and its
      environment].

PMID- 15444268
TI  - [Improvement of hygienic control of milk].

PMID- 15444269
TI  - [Cancer in pregnancy].

PMID- 15444270
TI  - [Pregnancy and pulmonary tuberculosis].

PMID- 15444271
TI  - [Two year results of the treatment of alcoholism in Bratislava region].

PMID- 15444272
TI  - [Success of the Hungarian scientist in the control of coccidiosis].

PMID- 15444273
TI  - [Conference of pediatriciants in Bratislava].

PMID- 15444274
TI  - [Significance of health education in the activities of a physician].

PMID- 15444275
TI  - [General principles in traumatology with special reference to fractures and first
      aid].

PMID- 15444276
TI  - [Treatment of pseudoarthrosis of the long bones].

PMID- 15444277
TI  - [Penicillin in the treatment of open fractures].

PMID- 15444279
TI  - [Prevention of trauma in metallurgy].

PMID- 15444278
TI  - [Treatment of burns].

PMID- 15444280
TI  - [Anticoagulant therapy in surgery].

PMID- 15444281
TI  - [Conference of physicians employed in metallurgical industry, 13 - 15 July,
      1951].

PMID- 15444282
TI  - [Soviet internal medicine - example for Czechoslovakia].

PMID- 15444283
TI  - [Occupational dermatoses in medical workers].

PMID- 15444284
TI  - [Vaginal cytology and its practical application].

PMID- 15444285
TI  - [Articulation disorders and their correction].

PMID- 15444286
TI  - [Foreign bodies in the urinary bladder].

PMID- 15444287
TI  - [Retroperitoneal skiagraphy].

PMID- 15444288
TI  - [October Revolution and public health].

PMID- 15444289
TI  - [Pathogenesis of hypertension].

PMID- 15444290
TI  - [Problem of infant mortality].

PMID- 15444291
TI  - [Wounds of the thorax and the intrathoracic organs].

PMID- 15444292
TI  - [Early diagnosis of tumors of the bladder].

PMID- 15444293
TI  - [New aspects in neurasthenia].

PMID- 15444294
TI  - [Practical considerations on group sensitization in diagnosis and prevention of
      allergic dermatoses].

PMID- 15444295
TI  - [Protection from roentgen rays].

PMID- 15444296
TI  - [Czechoslovakian-Soviet medical days].

PMID- 15444297
TI  - [Application of the Pavlovian theory in otorhinolaryngology].

PMID- 15444298
TI  - [Comparative studies on milk pasteurization with special reference to phosphatase
      test according to Michlin and Slygin].

PMID- 15444300
TI  - [Case of tularemia angino-bubonica].

PMID- 15444299
TI  - [Application of the microscopic method in hygienic milk examination].

PMID- 15444301
TI  - [Cases of syphilis].

PMID- 15444302
TI  - [Examination of patients suspected of diseases of leptospiral etiology].

PMID- 15444303
TI  - [Transfer of tissue in plastic surgery; general considerations].

PMID- 15444304
TI  - [General anesthesia in surgery of tumors of the jaws].

PMID- 15444305
TI  - [Root canal therapy with the aid of calcium hydroxide; clinical and
      histological].

PMID- 15444306
TI  - [Pseudo-tumor of the masseter bed; residual abscess].

PMID- 15444307
TI  - [General considerations on taking impressions in Kerr's paste in additional total
      prosthesis].

PMID- 15444308
TI  - [Endocarditis lenta consecutive to dental operations].

PMID- 15444309
TI  - [Practical data on trichoroethylene anesthesia].

PMID- 15444310
TI  - [Trichloroethylene analgesia in children].

PMID- 15444311
TI  - [Oral and genital manifestations in phenolphtalein intolerance].

PMID- 15444312
TI  - [Comparative study on bucco-dental abnormalities in a group of normal children
      and in a group of children with psychomotor retardation].

PMID- 15444313
TI  - [Case of multiple melanous tumors of the palate].

PMID- 15444314
TI  - [Not Available].

PMID- 15444315
TI  - [Observation on intra-arterial resuscitation].

PMID- 15444316
TI  - [Attempt to control bleeding by a hypotensive drug].

PMID- 15444317
TI  - [Analysis of 166 observations of controlled hypotension].

PMID- 15444318
TI  - [Decrease of bleeding by the technic of controlled hypotension; study of 72
      observations, 45 in pelvic surgery].

PMID- 15444319
TI  - [Contribution to the study of the effects of pentamethonium].

PMID- 15444320
TI  - [Weight method of evaluation of surgical hemorrhage systematic utilization of
      hexamethonium salts in pulmonary surgery].

PMID- 15444321
TI  - [First results of the use of hexamethonium in heart surgery].

PMID- 15444322
TI  - [Hexamethonium in neurosurgery].

PMID- 15444323
TI  - [Mechanism of action of methonium compounds].

PMID- 15444324
TI  - [Surgical sequellas observed in 24 patients subjected by hexamethonium].

PMID- 15444325
TI  - [Use of hexamethonium in digestive surgery with open thorax].

PMID- 15444326
TI  - [Curarization by the rectal route].

PMID- 15444327
TI  - [Experimental analgesia action of some derivatives of oxazolidine-dione].

PMID- 15444328
TI  - [Intensification of the local anesthetic power of cocaine by purified cajeput
      oil].

PMID- 15444329
TI  - [Attempt at vasoplegia by associations of drugs].

PMID- 15444330
TI  - [Hibernation and cerebral lesions].

PMID- 15444331
TI  - [Hibernation and meningitis].

PMID- 15444332
TI  - [Note on the utilization of nontransfusable preserved blood in protein therapy].

PMID- 15444333
TI  - [Small electric medical thermometer].

PMID- 15444334
TI  - [Biliary hemoglobinuric fever and quinine].

PMID- 15444335
TI  - [Rodenticides with an anticoagulant base].

PMID- 15444336
TI  - [The application of quinine for the relief of nocturnal cramps].

PMID- 15444337
TI  - [Quinine in the treatment of various painful syndromes].

PMID- 15444338
TI  - [Protection of thousands of Africans from malaria through agency of the World
      Health Organization].

PMID- 15444339
TI  - [Treatment of malaria].

PMID- 15444340
TI  - [Sporadic malaria; critique of a case report].

PMID- 15444341
TI  - [The modern treatment of sprue].

PMID- 15444342
TI  - [Resuscitation in children and infants].

PMID- 15444343
TI  - [Nitrous oxide-dolosal association].

PMID- 15444344
TI  - [Trichloroethylene in infantile anesthesia].

PMID- 15444345
TI  - [Anti-emetic effect of antihistaminics].

PMID- 15444346
TI  - [Clinical; surgical trials with succinylcholine diiodide].

PMID- 15444347
TI  - [Prevention of postoperative thromboembolic complications].

PMID- 15444348
TI  - [Practical notes on anesthesia in psychosurgery].

PMID- 15444349
TI  - [Modifications of circulatory hydraulics during spinal anesthesia in cardiac
      decompensation; indications and contraindications].

PMID- 15444350
TI  - [Tetanus and autonomic block; recovery].

PMID- 15444351
TI  - [The etiology of caries].

PMID- 15444352
TI  - [Subacute bilateral hypertrophy of the sublingual glands].

PMID- 15444353
TI  - [A case of an oral form of benign inoculation lymphoreticulosis].

PMID- 15444354
TI  - [The importance of medico-legal dentistry in identification; the idento
      stomogram; criminal cases solved by dentistry].

PMID- 15444355
TI  - [Comments on solid dentigerous adamantinomata].

PMID- 15444356
TI  - [Two new cases of cleft palate resulting from operations for harelip closed by
      cutaneous tube grafts].

PMID- 15444357
TI  - [Trauma causing impaction of teeth in the tongue and under the vestibular
      mucosa].

PMID- 15444358
TI  - [Closure of congenital cleft palate by cutaneous tube graft].

PMID- 15444359
TI  - [Conference of public health workers in Prague, 6-7 March 1952].

PMID- 15444360
TI  - [Legislations order and instructions].

PMID- 15444361
TI  - [In memory of Bohuslav Albert].

PMID- 15444362
TI  - [Public health research plans].

PMID- 15444363
TI  - [Works of the commission problem task and publication of research tasks].

PMID- 15444364
TI  - [Preparation of the research plan for 1952 by the Ministry of Health].

PMID- 15444365
TI  - [Wages for public health workers].

PMID- 15444366
TI  - [Legislations, orders and instructions].

PMID- 15444367
TI  - [Popularization of our causes].

PMID- 15444368
TI  - [Public health commissions in USSR].

PMID- 15444369
TI  - [Institute for agricultural medicine in Lublin].

PMID- 15444370
TI  - [Role of physicians in enforcing discipline].

PMID- 15444371
TI  - [Opening of the hygienic-epidemiological department at the Medical School of
      Prague].

PMID- 15444372
TI  - [Importance of the new department at the medical school].

PMID- 15444373
TI  - [Effect of environment in man].

PMID- 15444374
TI  - [Legislation on hygienic and anti-epidemic care].

PMID- 15444375
TI  - [Legislations, instructions, and orders].

PMID- 15444376
TI  - [Activities of Dr. B. Albert at the Ministry of Health].

PMID- 15444377
TI  - [Organization of preventive and therapeutic care].

PMID- 15444378
TI  - [Demonstration of variations in the mechanism of action of hypnotics by in vitro
      modifications in the calcium ion content of the nutritive medium].

PMID- 15444379
TI  - [Technic and results of artificial hibernation; its place in current practice].

PMID- 15444380
TI  - [Some principles of reanimation].

PMID- 15444381
TI  - [Some comments on the use of cyclopropane for fifteen years].

PMID- 15444382
TI  - [Pituitary-adrenal interrelations during hibernation].

PMID- 15444383
TI  - [Action of potentialized anesthesia and of hibernation of experimental myocardial
      infarction].

PMID- 15444384
TI  - [Hibernation for a serious prolonged coma complicating a Sakel treatment].

PMID- 15444385
TI  - [Gametocide properties of the antimalarials].

PMID- 15444386
TI  - [Kala-azar and malarial flocculation].

PMID- 15444387
TI  - [A strange claim of priority; quinine, a German discovery].

PMID- 15444388
TI  - [Studies on changes of position of various points of the fronto-facial profile in
      growth].

PMID- 15444389
TI  - [Index of two characters in anthropometric cranio-facial analysis].

PMID- 15444390
TI  - [Dental organization and education in United States].

PMID- 15444391
TI  - [Case of constriction of the jaw of extra-articular origin].

PMID- 15444392
TI  - [Observation on two cases of malignant histiocytary reticulosis or Letterer-Siwe
      disease].

PMID- 15444393
TI  - [Buccal lichen planus and cancer].

PMID- 15444394
TI  - [Leukoplasia and cancer].

PMID- 15444396
TI  - [Case of acute parotitis].

PMID- 15444395
TI  - [Bilateral jugal erosive lichen planus resistant to treatment during two years;
      appearance of spino-cellular epithelioma on the right cheek].

PMID- 15444397
TI  - [Case of cheilitis].

PMID- 15444398
TI  - [Cystic tumor invading the maxilla].

PMID- 15444399
TI  - [Observations on paradental cyst developing in the nassal fossae through the
      inferior meatus of the septum].

PMID- 15444400
TI  - [Dental aspects in prevention of infectious endocarditis].

PMID- 15444401
TI  - [Palliative treatment of facial paralysis].

PMID- 15444402
TI  - [Some considerations regarding primary buccal tuberculosis in adults].

PMID- 15444403
TI  - [Malaria prophylaxis in Tananarive in 1951; epidemiology and demography].

PMID- 15444404
TI  - [Antimalarial program of the Economic Cooperation Administration in Indochina].

PMID- 15444406
TI  - [The use of insectifuge products against sandflies].

PMID- 15444405
TI  - [Quinine is not abortive].

PMID- 15444407
TI  - [Is there any vital difference among the various species of mosquitoes?].

PMID- 15444408
TI  - [Colloidal quinine; critical review].

PMID- 15444409
TI  - [Implantation of resin in the region of the face and maxilla; clinical and
      histological results].

PMID- 15444410
TI  - [The retention of temporary molars].

PMID- 15444411
TI  - [The periodontium diseases of keratosis palmaris and plantaris; Meleda's
      disease].

PMID- 15444412
TI  - [Fistulas of Stenson's duct].

PMID- 15444413
TI  - [An original method for the reconstruction of the superior alveolar crest; an
      original method for the treatment of mandibular prognathism].

PMID- 15444414
TI  - [Atypical ectodermal polydysplasia with myxedema; effects of thyroxin therapy].

PMID- 15444415
TI  - [Tetanus and wisdom tooth emergence symptom].

PMID- 15444416
TI  - [An observation raising the problem of the malignant transformation of a large
      paradental cyst].

PMID- 15444418
TI  - [Leucosarcoma of buccal origin].

PMID- 15444417
TI  - [A case of cleido-cranial dysostosis].

PMID- 15444419
TI  - [Lymphosarcoma of gingival origin in a child of five].

PMID- 15444420
TI  - [Present status of analgesia and anesthesia in obstetrics].

PMID- 15444422
TI  - [Principles of psychosomatic anesthesiology].

PMID- 15444421
TI  - [Experimental hypnotic habituation].

PMID- 15444423
TI  - [Standardization of anesthetic gas cylinders and anesthetic apparatus].

PMID- 15444424
TI  - [Anesthetic apparatus valve; critical study].

PMID- 15444425
TI  - [Psycho-pedagogic sequella of certain interventions in children].

PMID- 15444426
TI  - [Note on the utilization of largactil (4560 RP) as potentiator of analgesics in
      painful cancer resistant to opiates].

PMID- 15444427
TI  - [Divinyl ether in anesthesia in children; pharmacological study].

PMID- 15444428
TI  - [Divinyl ether in anesthesia in adults].

PMID- 15444429
TI  - [Potentialized curarizing association; brevatonal and mediatonal].

PMID- 15444430
TI  - [Comet electropneumatic tensiometer].

PMID- 15444431
TI  - [Death 10 hours after right pneumonectomy for cancer, due to the absence of
      return of respiratory automatism].

PMID- 15444432
TI  - [Dental inclusions in a dermoepidermoid cyst of the ovary].

PMID- 15444433
TI  - [Reflections on two paradental cysts of the lower maxilla].

PMID- 15444435
TI  - [Extraction of dental roots: alveolectomy by alveolar route].

PMID- 15444434
TI  - [Allergic manifestations of the dental apparatus].

PMID- 15444436
TI  - [Adamantinomas].

PMID- 15444437
TI  - [Malaria in Mexico].

PMID- 15444438
TI  - [Prophylaxis and sensitivity to hematozoic parasites].

PMID- 15444439
TI  - [Malaria prevention in Alsace].

PMID- 15444440
TI  - [Craniomaxillary anchorage fastened to an individual plaster helmet].

PMID- 15444441
TI  - [New polarographic studies of the human gingiva].

PMID- 15444442
TI  - [Histologic examination of a curious case of odontoma].

PMID- 15444443
TI  - [Notes on the establishment of a formula for dental eruption].

PMID- 15444444
TI  - [A case for diagnosis: palatine ulceration of reflex origin?].

PMID- 15444445
TI  - [A case of nystagmus of the palatine velum].

PMID- 15444446
TI  - [Polyalveolysis in two children having palmoplantar keratodermia].

PMID- 15444447
TI  - [Is there a general syndrome of allergic order connected with oropharyngeal focal
      infection?].

PMID- 15444448
TI  - [Two cases of cephalic tetanus].

PMID- 15444449
TI  - [On the existence of posterior median fissural cysts of the palate; presentation
      of a case].

PMID- 15444450
TI  - [Malocclusion caused by adamantinoma and dental germ diseases].

PMID- 15444451
TI  - [Salivary lithiasis; actinomycotic origin].

PMID- 15444452
TI  - [Primary fluorescence of the gelatinous plaques of Leon Williams].

PMID- 15444453
TI  - [Embryogenesis of the nasopalatine canal].

PMID- 15444454
TI  - [Two cases of perforation of the median palate].

PMID- 15444455
TI  - [A case of primary tuberculous infection of the buccal mucosa].

PMID- 15444456
TI  - [Parodontosis].

PMID- 15444457
TI  - [Present state of analgesia and anesthesia in obstetrics].

PMID- 15444458
TI  - [Artificial hibernation in neurotoxicoses in infants].

PMID- 15444459
TI  - [Relation of constitution to action in the series of barbiturates and of
      thiobarbiturates with alcoyl root ramified into alpha].

PMID- 15444460
TI  - [Barbiturate of short duration effect].

PMID- 15444461
TI  - [Effect of d-tubocurarine on pressure regulation].

PMID- 15444462
TI  - [Effect of hexamethonium on histochemistry of the adrenal gland in stress].

PMID- 15444463
TI  - [Effect of ganglion blocking agents on urinary neutral 17-ketosteroids].

PMID- 15444464
TI  - [Considerations on a new electric defibrillator].

PMID- 15444465
TI  - [Anesthesia in surgery of hydatid cysts of the lungs].

PMID- 15444466
TI  - [Thyroid bodies in artificial hibernation].

PMID- 15444467
TI  - [Adreno-pituitary axis in hibernation].

PMID- 15444468
TI  - [Heart in artificial hibernation].

PMID- 15444469
TI  - [Protection of the heart in experimental cardiovascular surgery; technics].

PMID- 15444470
TI  - [Role of methonium in association of drugs depressing the autonomic nervous
      system; 140 observations].

PMID- 15444472
TI  - [Artificial hibernation and hyperglycemia].

PMID- 15444471
TI  - [Fatal accident following anesthesia with choropromazine premedication].

PMID- 15444473
TI  - [Nerve blocking in delirium tremens].

PMID- 15444474
TI  - [Cranial injury; treatment of grave shock and of commotional syndrome by
      hibernation].

PMID- 15444475
TI  - [Utilization of artificial hibernation in the treatment of prolonged insulin coma
      seemingly irreversible].

PMID- 15444476
TI  - [Coma due to carbon dioxide and artificial hibernation].

PMID- 15444477
TI  - [Death due to right pneumonectomy].

PMID- 15444478
TI  - [Degree of curarization with mediational].

PMID- 15444479
TI  - [The oral humor].

PMID- 15444480
TI  - [The use of onlays as bridge abutments; indications and contra-indications].

PMID- 15444481
TI  - [Primary mucosal scleroderma; development since 1946].

PMID- 15444482
TI  - [Study on periodontal disease].

PMID- 15444483
TI  - [Suppurating disease of a cervical lymph node, the only clinical manifestation of
      tularemia].

PMID- 15444484
TI  - [Two mesiodens situated head to foot in the maxilla].

PMID- 15444485
TI  - [Osseous xanthomatosis with maxillary and iliac localizations].

PMID- 15444486
TI  - [Survey of plastic and maxillo-facial surgery in England].

PMID- 15444487
TI  - [The airdent unit; analysis and possibilities].

PMID- 15444488
TI  - [Treatment of pyorrhea by sodium hypochlorite].

PMID- 15444489
TI  - [Autoplasty after the Hungarian method].

PMID- 15444490
TI  - [Dyskinesia of the tongue: clinical study of 17 cases of abnormal movements of
      the tongue and peri-buccal muscles of post-encephalitic nature].

PMID- 15444491
TI  - [Outline of past and present uses of quinine].

PMID- 15444492
TI  - [Osseous grafting in maxillo-facial surgery].

PMID- 15444493
TI  - [Filling and sustaining grafts in repair of contour of the face with special
      reference to utilization of heterogenous grafts and of refrigerated cartilage].

PMID- 15444494
TI  - [Grafting and plastic surgery of the skin in surgery of the face; present state
      of the problem].

PMID- 15444495
TI  - [Dental implantations and grafting or inclusion of supports of artificial teeth].

PMID- 15444496
TI  - [Fibrous osteopathies of the jaws].

PMID- 15444497
TI  - [Critical studies on recent methods of impression taking; technic and critique of
      hydrocolloids in conjoint prostheses].

PMID- 15444498
TI  - [Impressions in adjoint partial prostheses].

PMID- 15444499
TI  - [Critical study of recent methods of impression taking in full adjoint
      prosthesis].

PMID- 15444500
TI  - [Curarization in the waking state and cataract surgery].

PMID- 15444501
TI  - [The indications and dangers of preoperative blood transfusion].

PMID- 15444502
TI  - [Continuous oxymetry in thoracic surgery].

PMID- 15444503
TI  - [Observations on sodium 5-ethyl-5-(1-ethylbutyl)-2-thiobarbiturate].

PMID- 15444504
TI  - [The influence of age of rats on their sensitivity to some hypnotics].

PMID- 15444505
TI  - [Comments on a muscle relaxant with short action, brevatonal].

PMID- 15444506
TI  - [Supplementary note on the subject of the association of muscle relaxants].

PMID- 15444507
TI  - [Another local anesthetic, diethylaminoethyl p-isopropylbenzoate hydrochloride].

PMID- 15444508
TI  - [General anesthesia in otorhinolaryngology at Massachusetts Eye and Ear
      Infirmary].

PMID- 15444509
TI  - [The prevention of disturbances of rhythm in well-regulated cardiac surgery;
      experimental study and clinical applications].

PMID- 15444510
TI  - [Phenergan and blood preservation].

PMID- 15444511
TI  - [Muscarine-like effect of succinylcholine perfusions].

PMID- 15444512
TI  - [Postoperative delirium and neuroplegia].

PMID- 15444513
TI  - [The antagonism between phenergan and cardiazol].

PMID- 15444514
TI  - [Gangrene of the fingers after paravenous injection of meperidine with diparcol].

PMID- 15444515
TI  - [Deglutition and malocclusion].

PMID- 15444516
TI  - [Osteosynthesis with wire in the treatment of fractures of the mandible].

PMID- 15444517
TI  - [Results of fifteen resections of the inferior alveolar nerve in cases of
      essential facial neuralgia].

PMID- 15444518
TI  - [Crown with ceramic facings].

PMID- 15444519
TI  - [The use of an external fixator in the treatment of a case of fracture of the
      angle of the mandible].

PMID- 15444520
TI  - [Hemangioma of the mandible].

PMID- 15444521
TI  - [Extensive subacute ulcerative tuberculosis of the labial and jugal mucosa
      treated by isonicotinic acid hydrazide].

PMID- 15444522
TI  - [Tertiary syphilitic glossitis treated by penicillin].

PMID- 15444523
TI  - [A case of iritis].

PMID- 15444524
TI  - [Excision of the submaxillary gland].

PMID- 15444525
TI  - [The practice of orthodontics in hospitals].

PMID- 15444526
TI  - [A case of impaction of the lower permanent first molar and several cases of
      retention of the lower second and third molars, in three cases caused by
      adamantinoma].

PMID- 15444527
TI  - [Not Available].

PMID- 15444528
TI  - [Craniofacial thrombophlebitis of buccodental origin].

PMID- 15444529
TI  - [Dental prosthesis with mesial spring].

PMID- 15444530
TI  - [Enlarged roentgenography of the mandible].

PMID- 15444531
TI  - [A case of purpura fulminans diagnosed by orthodontic examination].

PMID- 15444532
TI  - [Sudoriparous tumor of the upper lip].

PMID- 15444533
TI  - [Two tumors of the lip; necessity of histological examination].

PMID- 15444534
TI  - [A case of Marfan's disease].

PMID- 15444535
TI  - [Three cases of mandibular fracture treated by homeopathy].

PMID- 15444536
TI  - [Cure of Escat's phlegmon by homeopathy].

PMID- 15444537
TI  - [Not Available].

PMID- 15444538
TI  - [Progressive facial hemiatrophy].

PMID- 15444539
TI  - [Structure of Tomes' fiber].

PMID- 15444540
TI  - [Benign tumors of the gums of infants].

PMID- 15444541
TI  - [A case of gingival hyperplasia during acute leukemia].

PMID- 15444542
TI  - [Conservative treatment of the teeth after radicular operative perforation].

PMID- 15444543
TI  - [Stimulant electrotherapy].

PMID- 15444544
TI  - [Structural examination of short-wave apparatus by the Physikalish-Technische
      Bundesanstalt].

PMID- 15444545
TI  - [Repetitorium of concepts in physical medicine].

PMID- 15444546
TI  - [Anesthesiological development in cerebral surgery].

PMID- 15444547
TI  - [Recent sata on the mechanisms in the variations in cerebrospinal fluid and
      venous pressures under the influence of certain general anesthetics].

PMID- 15444548
TI  - [Critical analysis on the effect of artificial hibernation in 19 cases of pain of
      the cerebral trunk after traumatism; selected for their severity from among 270
      post-concussional comas].

PMID- 15444549
TI  - [Hibernotherapy in the prevention of paraplegia in clamping of the descending
      thoracic aorta].

PMID- 15444550
TI  - [Surgery and artificial hibernation].

PMID- 15444551
TI  - [The national file of blood donors].

PMID- 15444552
TI  - [How to determine the value of a new treatment].

PMID- 15444553
TI  - [Artificial hibernation in cardiac surgery].

PMID- 15444554
TI  - [Is premedication always necessary].

PMID- 15444555
TI  - [Considerations on the physiology of the fetus during anesthesia of the pregnant
      woman].

PMID- 15444556
TI  - [Renal effects of controlled hypotension in general anesthesia].

PMID- 15444557
TI  - [Technics for artificial hibernation; comparative experimental study].

PMID- 15444558
TI  - [Atropine and respiratory inhibition].

PMID- 15444559
TI  - [Not Available].

PMID- 15444560
TI  - [Infrared photometry especially adapted to determine the carbon dioxide in
      anesthesiology and in ventilation physiology].

PMID- 15444561
TI  - [Needle for continuous or interrupted intervenous perfusion].

PMID- 15444562
TI  - [Spontaneous ventricular defibrillation].

PMID- 15444563
TI  - [Hibernation and hemorrhagic shock].

PMID- 15444564
TI  - [Fibrous tumors of the buccal cavity].

PMID- 15444565
TI  - [A case of Sjoegren syndrome treated with cortisone].

PMID- 15444566
TI  - [Chronic maxillary sinusitis in children: anatomoclinical aspects].

PMID- 15444567
TI  - [Two special cases of ectopia of lower wisdom teeth].

PMID- 15444568
TI  - [X-rays in stomatology].

PMID- 15444569
TI  - [Not Available].

PMID- 15444570
TI  - [Lymphosarcoma of the jaws].

PMID- 15444572
TI  - [The teeth of the most ancient mammals, Microlestidae].

PMID- 15444571
TI  - [Glossodynia: sensation of burn in the oral cavity].

PMID- 15444573
TI  - [Not Available].

PMID- 15444574
TI  - [Cyst of the nasopalatine canal in totally, edentulous maxilla].

PMID- 15444575
TI  - [Not Available].

PMID- 15444576
TI  - [Surgical treatment of the malar bone].

PMID- 15444577
TI  - [Hereditary abnormality of the buccal mucosa: abnormal bands and frenula].

PMID- 15444578
TI  - [Cast crown: a technic for crown with root tenon (Richmond's type) easily and
      quickly applied and especially good in regard to results].

PMID- 15444579
TI  - [Not Available].

PMID- 15444580
TI  - [Vertical radiological examination of the cranium and the face].

PMID- 15444581
TI  - [A case of darmous: study of fluorine].

PMID- 15444582
TI  - [Reticulodental cyst developing at the upper right canine and causing ocular
      disorders].

PMID- 15444584
TI  - [Not Available].

PMID- 15444583
TI  - [The after-treatment of infantile paralysis with variable impulses of exponential
      current].

PMID- 15444585
TI  - [Heart damage after electrical accident].

PMID- 15444586
TI  - [Theoretical comments with reference to the effects of strong direct and
      alternating currents on humans].

PMID- 15444587
TI  - [Short wave hyperthermia therapy with the help of pyrostates].

PMID- 15444588
TI  - [Combined short wave hyperthermia-penicillin therapy of metaluetic diseases].

PMID- 15444589
TI  - [Six years of maxillo-facial practice in Indochina].

PMID- 15444590
TI  - [Two cases of fixed prothesis with stress-breakers].

PMID- 15444591
TI  - [A further case of congenital benign gingival tumor; the problem of granular
      cells].

PMID- 15444592
TI  - [Therapy of infections; value, prescription and limitations of the use of
      sulfonamides and antibiotics].

PMID- 15444593
TI  - [Role of the sympathetic nervous system in stomatology].

PMID- 15444594
TI  - [Etiological problems of the so-called congenital temporomandibular ankylosis].

PMID- 15444595
TI  - [Acrylic restoration of the face].

PMID- 15444596
TI  - [Restoration of vital posterior teeth after horizontal fracture].

PMID- 15444597
TI  - [Two cases of Albers-Schonberg disease: maxillo-dental lesions].

PMID- 15444598
TI  - [Chronic abscess of the tongue].

PMID- 15444600
TI  - [Not Available].

PMID- 15444599
TI  - [Two cases of mandibular osteomyelitis in children].

PMID- 15444601
TI  - [The effect of sex glands on sensitivity of the white rats to various hypnotics].

PMID- 15444602
TI  - [Late accidents due to desoxycorticosterone in surgical resuscitation].

PMID- 15444603
TI  - [Personal experiences in anesthesiology with two new synthetic curarizers:
      brevatonal and mediatonal].

PMID- 15444604
TI  - [The effect of sex hormones on hexobarbital activity in rat; duration of
      hexobarbital retention in rat].

PMID- 15444605
TI  - [Experimental studies on the site of injection in intra-arterial transfusion].

PMID- 15444606
TI  - [Prevention of postoperative vomiting by three retard antihistaminics].

PMID- 15444607
TI  - [Parenteral perfusions of fructose in surgery].

PMID- 15444609
TI  - [The measurement of gas output].

PMID- 15444608
TI  - [Truncal extradural anesthesia with pantocaine-plombe].

PMID- 15444610
TI  - [Induced anoxia and artificial hibernation; electroencephalographic study].

PMID- 15444611
TI  - [Reflexions of a provincial anesthetist on artificial hibernation and modern
      anesthetic procedures].

PMID- 15444612
TI  - [Anesthesia in 125 major operations in gastroenterology].

PMID- 15444613
TI  - [Eight cases of artificial hibernation in vascular surgery].

PMID- 15444614
TI  - [Experimental studies on interpretation of therapeutic activity of
      chlorpromazine].

PMID- 15444615
TI  - [Personal experience in anesthesia in major urological surgery].

PMID- 15444616
TI  - [The use of succinylcholine diiodide in general anesthesia in
      otorhinolaryngological endoscopies].

PMID- 15444617
TI  - [Inefficacy and danger of oxygen therapy; necessity of simultaneously assisted
      ventilation in anesthesia and in respiratory insufficiencies].

PMID- 15444618
TI  - [Two cases of severe cerebral concussion treated and cured by artificial
      hibernation].

PMID- 15444619
TI  - [Uterine rupture, hysterectomy, severe shock, artificial hibernation and cure].

PMID- 15444620
TI  - [Case of double indication of artificial hibernation].

PMID- 15444621
TI  - [Clinical aspects of modern electrotherapy of paralysis].

PMID- 15444622
TI  - [Ultrasonic therapy].

PMID- 15444623
TI  - [Seventieth anniversary of the Academician N. Gh. Lupu].

PMID- 15444624
TI  - [Prophylactic trends in internal medicine].

PMID- 15444625
TI  - [Pathogenetic prophylactic and therapeutic study of pneumoconioses].

PMID- 15444626
TI  - [Importance of pneumographical methods in clinical examination].

PMID- 15444627
TI  - [The effect of cerebral excitation states on a non-conditioned vascular reflex].

PMID- 15444628
TI  - [Compensatory mechanisms in pulmonary insufficiency].

PMID- 15444630
TI  - [Epidemic grippe].

PMID- 15444629
TI  - [Clinical importance of silicosis].

PMID- 15444631
TI  - [Role of the central nervous system in production of changes of arterial pressure
      in athletes].

PMID- 15444632
TI  - [Electrocardiographical changes in athletes; study of marathon runners and
      skiers].

PMID- 15444633
TI  - [Study of alkaline mineral water in aerosols in therapy of chronic
      bronchopulmonary diseases].

PMID- 15444634
TI  - [Study of work capacity in lung diseases].

PMID- 15444635
TI  - [Chronic interstitial pneumonia].

PMID- 15444636
TI  - [Trans-tracheal administration of penicillin (Macarov-Gurova method) in therapy
      of pulmonary suppurations].

PMID- 15444637
TI  - [Ten years of progress in medicine and health].

PMID- 15444638
TI  - [One-hundredth anniversary of the birth of the great Rumanian scholar, Victor
      Babes].

PMID- 15444640
TI  - [Poliomyelitis: current pathogenetic concept].

PMID- 15444639
TI  - [Current status of the medical therapy of hypertensive diseases].

PMID- 15444641
TI  - [Iron metabolism and pathogenesis of iron deficiency anemia].

PMID- 15444642
TI  - [Chronic histio-monocytic reticulosis].

PMID- 15444643
TI  - [Cavitary forms of primary pulmonary cancer; clinical and radiological aspects].

PMID- 15444644
TI  - [Anti-helminth preventive measures for use in rural areas].

PMID- 15444645
TI  - [Megaloblastosis in the light of recent research].

PMID- 15444646
TI  - [Giant follicular lymphadenopathy, Brill-Symmer's disease: lymphoblastoma,
      follicular lymphocytoma or follicular lymphoid sarcoma].

PMID- 15444648
TI  - [Study of hemolytic anemia associated with familial hemolytic jaundice].

PMID- 15444647
TI  - [Arterial pumping in therapy of chronic arterial obliterations in the extremities
      and its theoretical significance].

PMID- 15444649
TI  - [Study of vascular reflexes by means of digital plethysmography].

PMID- 15444650
TI  - [Popular methods of immunization against smallpox known in the rural areas of
      Rumania for a long time].

PMID- 15444651
TI  - [Osteotomy of the maxilla with special reference to total harelip].

PMID- 15444652
TI  - [Diagnosis and treatment of malignant tumors of the mouth, jaws and face].

PMID- 15444653
TI  - [Procedure of alternated triangles in plastic surgery of the maxillofacial
      region].

PMID- 15444654
TI  - [Pharyngoplasty and endotracheal anesthesia].

PMID- 15444655
TI  - [Mobilizing apparatus for the postoperative treatment of temporomandibular
      ankylosis].

PMID- 15444656
TI  - [1500 Grafts].

PMID- 15444657
TI  - [Radiography of the zygomato-malar region by verticosubmandibular incidence].

PMID- 15444658
TI  - [Treatment of isolated fracture of the zygomatic arch by Gillies' technic].

PMID- 15444659
TI  - [Plastic surgery: reflections on various cases operated in 1953].

PMID- 15444660
TI  - [Remarks on mandibular grafts].

PMID- 15444661
TI  - [Implantation of alloplastic substances in face and jaw].

PMID- 15444662
TI  - [Transplantation of impacted teeth].

PMID- 15444663
TI  - [Clinical and histological study of subperiosteal inclusions for prosthesis].

PMID- 15444664
TI  - [Osteoplasty of the mandible].

PMID- 15444665
TI  - [Temporo-maxillary ankylosis].

PMID- 15444666
TI  - [One stage subperiosteal tantalum implantation].

PMID- 15444667
TI  - [Therapeutic tissue and parodontosis].

PMID- 15444668
TI  - [Maxillofacial surgery during the 19th century and especially during the 2nd
      Empire].

PMID- 15444669
TI  - [New surgical treatment of fistulas of the canal of Steno].

PMID- 15444670
TI  - [Frequency of bifid root of the lower canine].

PMID- 15444671
TI  - [On the general etiology of pyorrhea].

PMID- 15444672
TI  - [Trichloroacetic acid in surgical and dermatologic treatment association of
      trichloroacetic acid with salicylic acid (ATS); great bactericidal value of 3%
      solutions].

PMID- 15444673
TI  - [Conservative surgical treatment of adamantinoma of the jaw].

PMID- 15444674
TI  - [Technic of fixation of bone fragments of the mandible in osteoplasty].

PMID- 15444676
TI  - [A case of osteoma of the condyle: intervention, outcomes].

PMID- 15444675
TI  - [Some cases of localized osseous dystrophy].

PMID- 15444678
TI  - [Conservative treatment of a voluminous coronodental cyst in a 9 year old child].

PMID- 15444677
TI  - [Osteoma of the  temporo-maxillary region].

PMID- 15444679
TI  - [Subacute lupus erythematosus of the buccal mucosa].

PMID- 15444680
TI  - [Germectomy: follicular cysts of the alveolar region].

PMID- 15444681
TI  - [Treacher-Collins syndrome].

PMID- 15444682
TI  - [Not Available].

PMID- 15444683
TI  - [Methods of impression taking from the point of view of physical laws].

PMID- 15444684
TI  - [New technic of parallelism for fixed bridge with multiple abutments].

PMID- 15444685
TI  - [Impression taking of inlays and onlays by alginates].

PMID- 15444686
TI  - [Study of the quality of the mucosa before impression taking].

PMID- 15444687
TI  - [Immobilization of full lower prosthesis by Ivy ligatures attached to the
      prosthesis by a new method].

PMID- 15444688
TI  - [Utilization of magnets in maxillofacial prosthesis].

PMID- 15444689
TI  - [Velo-palatine prosthesis and phonetics].

PMID- 15444690
TI  - [Attempt at orthodontic nosology based on statistical study of 500 personal
      cases].

PMID- 15444691
TI  - [Long span bridges].

PMID- 15444692
TI  - [Critical study of different stress breakers applied to non-rigid and rigid
      bridges].

PMID- 15444693
TI  - [Observation of a case of fibrous osteitis].

PMID- 15444694
TI  - [Possibility of focal infection by tooth with vital pulp].

PMID- 15444696
TI  - [Use of succinylcholine diiodide in convulsion therapy with pentylenetetrazole].

PMID- 15444695
TI  - [An antagonist of d-tubocurarine: pyridostigmine (mestinon) or RO 1-5130].

PMID- 15444697
TI  - [Importance of broncho-motricity and the relations between bronchial and
      pulmonary circulation in anesthesia, in open thorax surgery and in hibernation].

PMID- 15444698
TI  - [Hypothermic neuroplegia, called artificial hibernation, with dihydrogenated
      derivatives of ergot of rye; physiological study].

PMID- 15444699
TI  - [The heart in artificial hibernation].

PMID- 15444700
TI  - [Endocrine reactions to aggression under artificial hibernation].

PMID- 15444701
TI  - [Electroencephalographic control in artificial hibernation].

PMID- 15444702
TI  - [Artificial hibernation without chlorpromazine; first clinical trials (general
      surgery)].

PMID- 15444703
TI  - [Hydergine in neurosurgery].

PMID- 15444704
TI  - [Role of hibernation in injuries of the autonomic centers].

PMID- 15444705
TI  - [Controlled hypotension with arfonad, a ganglion blocking agent with temporary
      action; first clinical results].

PMID- 15444706
TI  - [First attempts of controlled hypotension with arfonad].

PMID- 15444707
TI  - [Experimental study of elimination of dihydrone pectinate, a central analgesic
      with prolonged action].

PMID- 15444708
TI  - [The characteristic curve of carbon dioxide absorption by soda lime; technic of
      production and discussion].

PMID- 15444709
TI  - [Technic of using ganglion blocking agents in otorhinolaryngology].

PMID- 15444710
TI  - [Modifications of the biological equilibrium in thoracic surgery].

PMID- 15444711
TI  - [Engstrom's universal respirator, apparatus of ventilatory prosthesis].

PMID- 15444712
TI  - [Assemblage of equipment for surgical surveillance].

PMID- 15444713
TI  - [A measurement table for physiologic controls].

PMID- 15444714
TI  - [Artificial hibernation in a case of serious spinal cord injury].

PMID- 15444715
TI  - [The present state of electroconvulsive therapy].

PMID- 15444716
TI  - [Artificial respiration by electric stimulation of the phrenic nerve].

PMID- 15444717
TI  - [Radiography of the mandibular condyle by anterior-posterior transorbital
      projection; importance, technic, indications].

PMID- 15444718
TI  - [The necessity of bone resection in surgery of congenital cleft palate].

PMID- 15444719
TI  - [Gingivitis symptomatic of intestinal parasitosis].

PMID- 15444720
TI  - [A moulded cap in the orthodontic treatment of unerupted teeth].

PMID- 15444721
TI  - [A case of permanent constriction of the jaws of muscular and osteoarticular
      origin].

PMID- 15444722
TI  - [Surgical treatment of large maxillary cysts].

PMID- 15444723
TI  - [An abscess at the base of the tongue].

PMID- 15444724
TI  - [Fractures of the mandibular condyle; therapeutic comments on 50 cases].

PMID- 15444725
TI  - [Basal metabolism during artificial hibernation; 4 case reports].

PMID- 15444726
TI  - [Preliminary note on ultra-fastacting intravenous barbiturate, the J.L. 1179
      ter].

PMID- 15444727
TI  - [Some indications of intravenous mebubarbital].

PMID- 15444728
TI  - [Not Available].

PMID- 15444729
TI  - [Not Available].

PMID- 15444730
TI  - [A new local anesthetic: benzoic acid 3-diethylamino-1-phenylpropyl ester
      hydrochloride].

PMID- 15444731
TI  - [Post-anesthetic agitation in curare anesthesia].

PMID- 15444732
TI  - [Modification of the action of local anesthetics by isoniazid].

PMID- 15444733
TI  - [Anesthesia without intubation (free air anesthesia) in surgery of the head].

PMID- 15444735
TI  - [The Laborit-Cuvier atmospheric hibernator].

PMID- 15444734
TI  - [Death during artificial hibernation for thyroid surgery with cardiac
      complications].

PMID- 15444736
TI  - [The Philips thermometer-register].

PMID- 15444737
TI  - [Ultrashort waves and ultrasonics in medicine].

PMID- 15444738
TI  - [Preventive trend in internal medicine].

PMID- 15444739
TI  - [Localization of functions in the cerebral cortex and its functional structure].

PMID- 15444740
TI  - [Renal pressor mechanisms and their role in the pathogenesis of hypertensive
      disorders].

PMID- 15444741
TI  - [Some basic problems in rheumatic diseases].

PMID- 15444742
TI  - [Testicular hyaluronidase in therapy of rheumatism].

PMID- 15444743
TI  - [Investigation of renal function with the aid of plasma purification methods;
      measurement of glomerular infiltrates with sodium hyposulfite].

PMID- 15444744
TI  - [Acute renal insufficiency: practical rules, media and criteria in its therapy].

PMID- 15444745
TI  - [Errors in diagnosis and therapy of rheumatic diseases].

PMID- 15444746
TI  - [Hand-shoulder syndrome in the pathology of visceral infarcts].

PMID- 15444747
TI  - [Rheumatism in forest workers].

PMID- 15444748
TI  - [Orthopedic surgery in chronic rheumatism of the extremities].

PMID- 15444749
TI  - [Medical evaluation of work capacity in rheumatic diseases].

PMID- 15444750
TI  - [A point in the controversial discussion of the etiology of pellagra; the works
      of Dr. I. Neagoe].

PMID- 15444751
TI  - [Use of a portable device for study of higher nervous activity in humans
      according to the Ivanov-Smolenski method].

PMID- 15444752
TI  - [Granular cell tumors of the oral cavity].

PMID- 15444753
TI  - [The so-called bactericide action of human saliva].

PMID- 15444754
TI  - [Various methods of reconstitution of the first upper premolar].

PMID- 15444755
TI  - [Clinical use of craniomandibular fixation with individual plaster casque].

PMID- 15444756
TI  - [Two cases of conjoint protheses realized at the Institut de Stomatologie].

PMID- 15444757
TI  - [A case of late mandibular osteoradionecrosis; trial of tissue therapy].

PMID- 15444758
TI  - [First application of Roudko's (U.S.S.R.) apparatus in France; external fixator
      for mandibular fracture].

PMID- 15444759
TI  - [A case of thrombophlebitis of the facial and ophthalmic veins].

PMID- 15444760
TI  - [Diagnosis of a vast jugal ulceration].

PMID- 15444761
TI  - [A case of facial tumor; Recklinghausen's neurofibromatosis].

PMID- 15444762
TI  - [On the vertico submandibular incidence].

PMID- 15444763
TI  - [Cast caps in orthondontic treatment of upper impacted canine teeth; presentation
      of two clinical cases].

PMID- 15444764
TI  - [Atrophy of the ramus of the mandible subsequent to a condylar fracture in
      child].

PMID- 15444765
TI  - [A complicated case of face reconstruction].

PMID- 15444766
TI  - [Use of the external fixation method in a case of multiple fractures of the
      jaws].

PMID- 15444767
TI  - [Two cases of ocular disorders of dental origin].

PMID- 15444768
TI  - [Mixed tumor of the upper lip].

PMID- 15444769
TI  - [Hypothalamo-hypophysial neurosecretion during shock and controlled general
      hypothermia; experimental study].

PMID- 15444770
TI  - [Arterial transfusion and cardiac reanimation: effects of transfusion on coronary
      circulation in cardiac arrest].

PMID- 15444771
TI  - [Reanimation by intra-arterial route: experimental study of the mode of action].

PMID- 15444772
TI  - [Results of prognostic treatment of cardiac arrest: statistical study of the
      Centre Lyonnais de Chirurgie Cardio-Vasculaire].

PMID- 15444773
TI  - [Not Available].

PMID- 15444774
TI  - [Use of C. 5473 as anticholinergic in pre-anesthetic medication].

PMID- 15444775
TI  - [Emergency anesthesia with nesdonal-curare].

PMID- 15444776
TI  - [Local anesthesia in cesarian section].

PMID- 15444777
TI  - [Not Available].

PMID- 15444778
TI  - [Anesthesia with pentothal-curare-oxygen for caesarean section].

PMID- 15444779
TI  - [Role of the anesthesiologist in atomic war].

PMID- 15444780
TI  - [Not Available].

PMID- 15444781
TI  - [Intracardiac surgery].

PMID- 15444782
TI  - [Place of laudolissine among the present curarizing agents].

PMID- 15444783
TI  - [Two cases of prolonged hypotension after hexobarbital anesthesia].

PMID- 15444784
TI  - [Pharmacodynamic properties of 1-diethyl-amino-2-ethyl-N-dibenzoparathiazine
      hydrochloride (diethazine, 2987 R. P.)].

PMID- 15444785
TI  - [Various pharmacodynamic properties of N-ally-normorphine (nalorphine)].

PMID- 15444786
TI  - [The place of brachial plexus block in anesthesia].

PMID- 15444787
TI  - [Carbonarcosis; biological therapy of functional diseases].

PMID- 15444788
TI  - [Cerebral protection by hexamethonium during prolonged circulatory arrest].

PMID- 15444789
TI  - [Not Available].

PMID- 15444790
TI  - [Basic diparcol-dolosal anesthesia in geriatric surgery and in bad risk
      patients].

PMID- 15444791
TI  - [200 Cases of basic anesthesia (diparcol-dolosal) with local anesthesia in
      plastic surgery].

PMID- 15444792
TI  - [Association of diethazine and pethidine (dipdol) as basic anesthesia].

PMID- 15444793
TI  - [Critical study and review of hypophyseal-adrenal phenomena caused by nerve block
      and artificial hibernation].

PMID- 15444794
TI  - [Succinylcholine in pneumology and in thoracic surgery].

PMID- 15444795
TI  - [Variations of striated muscle imbibition under the influence of local
      anesthetics].

PMID- 15444796
TI  - [Early thermal disorders during high spinal sections].

PMID- 15444797
TI  - [A case of severe postoperative epilepsy treated by artificial hibernation].

PMID- 15444798
TI  - [Accident during the application of a new tube].

PMID- 15444799
TI  - [Intubation apparatus for general anesthesia in total laryngectomy after
      tracheotomy].

PMID- 15444800
TI  - [Cervicofacial actinomycosis: disease and syndrome].

PMID- 15444801
TI  - [Skeletal prosthesis; generalities].

PMID- 15444802
TI  - [The lower canine [tooth]].

PMID- 15444803
TI  - [Reconstruction of loss of the facial substance with flexible resin].

PMID- 15444804
TI  - [Fatal staphylococcemia after dental avulsion: a case of epiduritis].

PMID- 15444806
TI  - [Not Available].

PMID- 15444805
TI  - [Treatment of partial fractures of the upper maxilla with invasion of the malar
      bone].

PMID- 15444807
TI  - [Prevention of dental caries and the use of fluorine].

PMID- 15444808
TI  - [Critical study of prevention of dental caries by local application of fluorine].

PMID- 15444809
TI  - [Periodontal lesions in Paget's disease; comparison with darmous or Velu-Speder
      disease].

PMID- 15444810
TI  - [Velopalatine prosthesis and velopharyngoplasty].

PMID- 15444811
TI  - [Binocular magnifying-glass].

PMID- 15444812
TI  - [Quick recovery of a case of dyshidrosis treated with trichloroacetic and
      salicylic acid].

PMID- 15444813
TI  - [Reconstruction of the mandibular arch].

PMID- 15444814
TI  - [Stress-breaker for fixed bridges; its new adjusting spring device; its use in
      skeletal prostheses].

PMID- 15444815
TI  - [Dentition disorders and dental abnormalities in relation to radium therapy of
      lymphangioma of the cheek].

PMID- 15444816
TI  - [Biotypological report of a case of uniovular twins].

PMID- 15444817
TI  - [Use of alginates in stomatology].

PMID- 15444818
TI  - [Postoperative malformations of total harelip and cleft palate and their
      orthopedic treatment].

PMID- 15444819
TI  - [Root of the upper middle incisor].

PMID- 15444820
TI  - [Treatment of palatine injuries and destruction of the orbit by cylindrical trans
      sinusal and transjugal grafts].

PMID- 15444821
TI  - [Congenital absence of a mandibular condyle].

PMID- 15444822
TI  - [Mandibular growth].

PMID- 15444824
TI  - [Treatment of temporo-maxillary ankylosis].

PMID- 15444823
TI  - [Reconstruction of chin and controus of the horizontal branch of the inferior
      maxilla by bone grafts introduced through the mouth].

PMID- 15444825
TI  - [Two cases of diffuse gingival hyperplasia].

PMID- 15444826
TI  - [Histological contribution to the study of sulci].

PMID- 15444827
TI  - [Focal syndrome and rheumatism of dental origin].

PMID- 15444828
TI  - [Mixed tumor of the cheek with pulmonary and costal metastases].

PMID- 15444829
TI  - [Interpretation of the third upper incisor of young Leporidae].

PMID- 15444830
TI  - [Not Available].

PMID- 15444831
TI  - [Early rickets and barley-sugar teeth].

PMID- 15444832
TI  - [Cervico-facial actinomycosis; study of the evolution of pterygomaxillary types].

PMID- 15444833
TI  - [A case of lymphoreticulosarcome of cervical origin].

PMID- 15444834
TI  - [Presentation of a case of joint prosthesis].

PMID- 15444835
TI  - [Dental alterations in maxillary localization of eosinophilic granuloma].

PMID- 15444837
TI  - [Approaches to the malar bone].

PMID- 15444836
TI  - [Traumatic section of the duct of Steno].

PMID- 15444838
TI  - [Trismus, single symptom of fulminating tetanus].

PMID- 15444839
TI  - [Mandibular osteosynthesis].

PMID- 15444840
TI  - [Electroencephalographic, electrodermatographic and electromyographic changes
      induced by chlorpromazine].

PMID- 15444841
TI  - [Changes of the electrodermatogram, sudation and cutaneous temperature by
      chlorpromazine].

PMID- 15444842
TI  - [Not Available].

PMID- 15444843
TI  - [Hibernation in postoperative thyrotoxic crisis].

PMID- 15444844
TI  - [Leukocytes, erythrocytes and plasma proteins in anesthesia with hypothermia].

PMID- 15444845
TI  - [Clinical impressions from 350 venous perfusions of dextran].

PMID- 15444846
TI  - [Erythrocyte suspensions in rapid preoperative reglobulization].

PMID- 15444847
TI  - [Cardiac rhythm disorders and intracardiac pressures].

PMID- 15444848
TI  - [Anesthesia in the Low Countries].

PMID- 15444849
TI  - [Importance of measurement of neuromuscular excitability in anesthesiology].

PMID- 15444850
TI  - [Biological and therapeutic role of calcium salts in anesthesiology, artificial
      hibernation and surgical therapeutics].

PMID- 15444851
TI  - [Not Available].

PMID- 15444852
TI  - [Emergency controlled hypotension with methonium compounds for preoperative
      hemostasis].

PMID- 15444853
TI  - [Two stage hibernation for rupture of the spleen and postoperative delirium
      tremens].

PMID- 15444854
TI  - [A case of severe occlusive syndrome with spontaneous neurovegetative
      disconnection].

PMID- 15444855
TI  - [Technic for pharyngeal tamponage].

PMID- 15444856
TI  - [Pharmacology of procaine].

PMID- 15444857
TI  - [Ultrasonics in dentistry].

PMID- 15444858
TI  - [Value of dental arch indices].

PMID- 15444860
TI  - [Suturing after extraction of a mandibular third molar].

PMID- 15444859
TI  - [Perfected technic for a complete lower impression].

PMID- 15444861
TI  - [Chronic cervical adenitis, followed by gumma of the chin, revealing an oral
      tuberculous primo-infection dating from 30 months].

PMID- 15444862
TI  - [A new case of Romberg's disease (progressive facial hemiatrophy)].

PMID- 15444863
TI  - [Oral repercussions of an abdominal injury].

PMID- 15444864
TI  - [Not Available].

PMID- 15444865
TI  - [Hypesthesia of the chin nerve indicative of multiple sclerosis].

PMID- 15444866
TI  - [External fixation devices and Kirschner wires].

PMID- 15444867
TI  - [Temporomandibular ankylosis, sequela of hematogenous osteomyelitis of the
      condyle].

PMID- 15444868
TI  - [A case of Besnier-Boeck-Schaumann disease with cutaneous and labial
      manifestations].

PMID- 15444869
TI  - [Localized mandibular necrosis during trigeminal herpes].

PMID- 15444870
TI  - [A case of lymphosarcoma of the oral mucosa].

PMID- 15444871
TI  - [A case of sporotrichosis localized in the palate].

PMID- 15444872
TI  - [Cure and follow-up in a case of facial thrombophlebitis].

PMID- 15444873
TI  - [Phlegmon of the pterygomaxillary and temporal fossae].

PMID- 15444874
TI  - [Angiomas of the tongue].

PMID- 15444875
TI  - [The morphogenetic role of neuromuscular behavior].

PMID- 15444876
TI  - [Disorders in the oral phase of swallowing and muscular disorders; factors
      aggravating periodontal diseases].

PMID- 15444877
TI  - [The state of anesthesiology in Germany].

PMID- 15444878
TI  - [Not Available].

PMID- 15444879
TI  - [Not Available].

PMID- 15444880
TI  - [Modifications of the activity of local anesthetics on the rabbit cornea and the
      frog nerve in the presence of various wetting agents].

PMID- 15444881
TI  - [Physicochemical factors showing the influence of wetting agents on various types
      of local anesthesia].

PMID- 15444882
TI  - [Adverse affects of locoregional anesthesia and their treatments].

PMID- 15444883
TI  - [The kinetics of drug elimination: application to substances used in anesthesia].

PMID- 15444884
TI  - [Not Available].

PMID- 15444885
TI  - [Determination of pulse].

PMID- 15444886
TI  - [Not Available].

PMID- 15444887
TI  - [Not Available].

PMID- 15444888
TI  - [Not Available].

PMID- 15444889
TI  - [Not Available].

PMID- 15444890
TI  - [Increase of the anatomical respiratory dead space after injection of atropine in
      man and dog].

PMID- 15444891
TI  - [Increase of the anatomical respiratory dead space in dog in experimental
      hypothermia].

PMID- 15444892
TI  - [Treatment of acute respiratory insufficiency with special references to
      poliomyelitis].

PMID- 15444893
TI  - [Poliomyelitis in Denmark in 1952].

PMID- 15444894
TI  - [Circulatory accidents in the course of respiratory poliomyelitis].

PMID- 15444895
TI  - [Surveillance of patients in artificial respiration].

PMID- 15444896
TI  - [Not Available].

PMID- 15444897
TI  - [Swallowing disorders in poliomyelitis of children and their treatment].

PMID- 15444898
TI  - [Our experience of artificial respiration in thoracic surgery].

PMID- 15444899
TI  - [Treatment of respiratory insufficiency by rocking bed].

PMID- 15444900
TI  - [Present principles in the treatment of acute respiratory insufficiency in
      France].

PMID- 15444901
TI  - [Respiratory arrest during an injection of diethazine].

PMID- 15444902
TI  - [Technique of artificial respiration].

PMID- 15444903
TI  - [RENE LERICHE; 1879-1955].

PMID- 15444904
TI  - [Reduction of stress by hypometabolism; physiology and methods].

PMID- 15444905
TI  - [Artificial hibernation with ganglion blocking agents; report of 100 cases].

PMID- 15444906
TI  - [Experience of the Hospital das Clinicas de Sao Paulo with artificial hibernation
      and neuroplegia].

PMID- 15444907
TI  - [Treatment of acute and subacute common tetanus of the newborn and child; study
      of 14 personal cases].

PMID- 15444908
TI  - [Not Available].

PMID- 15444909
TI  - [Comparative effect of principal local anesthetics on the excitability of
      isolated nerve].

PMID- 15444910
TI  - [Action of local anesthetics on the excitability of isolated nerve separated from
      conjunctival sheath].

PMID- 15444911
TI  - [Poikilothermic effect of chlorpromazine].

PMID- 15444912
TI  - [Five cases of tetanus treated by neuro-vegetative blockage and curarization
      followed by cure].

PMID- 15444913
TI  - [Some difficult intubations].

PMID- 15444914
TI  - [Use of ganglioplegics in visceral pain].

PMID- 15444915
TI  - [Not Available].

PMID- 15444916
TI  - [Reflections on 2,000 anesthesia with curarization].

PMID- 15444917
TI  - [Preliminary note on a narcotic steroid: the sodium succinate of 21
      hydroxypregnandione].

PMID- 15444918
TI  - [Plan for the organization of an anesthesia recovery service in a private
      clinic].

PMID- 15444919
TI  - [Three thousand cases of potentialized anesthesia, 1952-1955].

PMID- 15444920
TI  - [Treatment of eclampsia by the methods of artificial hibernation; report of 52
      cases observed in four years].

PMID- 15444921
TI  - [Anesthesiological treatment of poisoning].

PMID- 15444922
TI  - [Variations of muscular excitability under the influence of some lytics].

PMID- 15444923
TI  - [Experimental study on cardiac resuscitation at normal temperature and in
      hypothermia by cytochrome C, A.T.P. and oxaloacetic acid].

PMID- 15444924
TI  - [Not Available].

PMID- 15444925
TI  - [Sleep induced by viadril (hemi-succinate of 21 hydroxypregnanedione) and its
      electroencephalographic picture; comparative study of certain electroclinical
      manifestations induced by penthiobarbital and viadril].

PMID- 15444926
TI  - [Not Available].

PMID- 15444927
TI  - [Feto-maternal iso-immunization and congenital hemolytic disease].

PMID- 15444928
TI  - [Some considerations on anesthesia and reanimation in child; a potentializing
      premedication, promethazine-chlorpromazine-atropine].

PMID- 15444929
TI  - [Calcium chloride as major treatment of cardiac inefficacy; experimental study,
      application in 25 cases of cardiac resuscitation].

PMID- 15444930
TI  - [Blood volume and mono-semi-carbazone of adrenochrome].

PMID- 15444931
TI  - [General anesthesia in stomatology].

PMID- 15444932
TI  - [Our clinical experience with succinylcholine iodide].

PMID- 15444933
TI  - [Controlled curarization with succinylcholine chloride].

PMID- 15444934
TI  - [An attempt to treat postoperative pulmonary atelectasis with streptokinase
      streptodornase aerosols].

PMID- 15444935
TI  - [A case of resistance to spinal anesthesia].

PMID- 15444936
TI  - [Prolonged epileptic crisis provoked by streptococcal septicemia; hibernation
      recovery].

PMID- 15444937
TI  - [Not Available].

PMID- 15444938
TI  - [Not Available].

PMID- 15444939
TI  - [Barbiturate antidotes].

PMID- 15444940
TI  - [Not Available].

PMID- 15444941
TI  - [Not Available].

PMID- 15444942
TI  - [Treatment of surgical thyrotoxicosis by vegetative neuroplegia and general
      hypothermia (artificial hibernation)].

PMID- 15444944
TI  - [Prevention of the operative diseases in cardiovascular surgery in the
      peroperative period].

PMID- 15444943
TI  - [Research on protection by RP 2831 (heptaminol) against cardio-respiratory
      depression due to two injectable barbiturates (penthiobarbital, mebubarbital)].

PMID- 15444945
TI  - [Neuromuscular excitability and dehydration syndrome].

PMID- 15444946
TI  - [Syndrome of late postoperative anoxia due to fatigue in certain thoracic
      surgical patients; preventive attempt].

PMID- 15444947
TI  - [Role of bronchoscopy in anesthesiology].

PMID- 15444948
TI  - [Controlled hypotension by ganglion blocking agents and cerebral circulation].

PMID- 15444949
TI  - [Electroencephalographic forms of several usual types of surgical anesthesia].

PMID- 15444950
TI  - [Survival of the spermatozoid of Bos taurus obtained in vitro with several
      derivatives of phenothiazine].

PMID- 15444951
TI  - [What has become of the pallor-hyperthermia syndrome in the operated infant].

PMID- 15444952
TI  - [Resuscitation of accident victims as task of the anesthesiologist].

PMID- 15444953
TI  - [Organization and function of mobile rescue units of the fire brigade].

PMID- 15444954
TI  - [Case of electrocorticography under controlled hypotension].

PMID- 15444955
TI  - [Experimental analgesic action of morpholyl-N-toctyl acetamide (TR 315)].

PMID- 15444957
TI  - [Deferred transfusion thanks to potentiated anesthesia].

PMID- 15444956
TI  - [Not Available].

PMID- 15444958
TI  - [Prolonged apnea caused by succinylcholine iodide, related to a lowered blood
      cholinesterase content].

PMID- 15444959
TI  - [Not Available].

PMID- 15444960
TI  - [Delirium provoked by intravenous therapy without sodium].

PMID- 15444961
TI  - [Comparative study of various granules of soda lime in view of establishing
      specifications of a granule for intubated respiratory apparatus].

PMID- 15444962
TI  - [Obtaining of biological conditions necessary to maintain the functional optimum
      of homeothermia in low temperatures].

PMID- 15444963
TI  - [Not Available].

PMID- 15444964
TI  - [Hydroxydione sodium (Viadril); clinical essays in neurosurgery].

PMID- 15444965
TI  - [Principles of a new explanation of the mechanism of artificial hibernation;
      action of chlorpromazine on water metabolism and its importance in the production
      of neuroplegic phenomena].

PMID- 15444966
TI  - [Cardiac metabolism in artificial hibernation].

PMID- 15444967
TI  - [Reactivity of the hypophysis and adrenals under neuroplegia, external
      refrigeration and artificial hibernation in rats].

PMID- 15444968
TI  - [Not Available].

PMID- 15444969
TI  - [Not Available].

PMID- 15444970
TI  - [A thiobarbiturate of short action, thiogenal].

PMID- 15444971
TI  - [Not Available].

PMID- 15444972
TI  - [Use in intubation of a new local anesthetic; tronothane].

PMID- 15444973
TI  - [Intracardiac surgery with exsanguinated heart under artificial hibernation; in
      dogs].

PMID- 15444974
TI  - Interstitial plasmacell pneumonia with Pneumocystis carinii.

PMID- 15444975
TI  - [Rupture of spleen in newborn with iso-immunisation hemolytic anemia].

PMID- 15444977
TI  - [Vasomotor paralysis in surgery; physiopathological study; indications and contra
      indications].

PMID- 15444976
TI  - [Experimental angiocardiographic study of air emboli in bloodless heart surgery].

PMID- 15444978
TI  - [Structural analogies and synergism of analgesic action.  I.  Determination of
      analgesic action with analgesic combinations and some types of structural
      analogues with spasmolytic properties after thermal stimulus].

PMID- 15444979
TI  - [Structural analogies and synergism of analgesic action.  II.  Determination of
      analgesic power after mechanical stimulus in mouse; application of the synergism
      phenomenon].

PMID- 15444980
TI  - [Precautions and care accompanying surgery in newborn].

PMID- 15444981
TI  - [Preoperative and postoperative care in mitral commissurotomy].

PMID- 15444982
TI  - [Peroperative examination of peripheral venous pressure].

PMID- 15444983
TI  - [Critical study of 40 cases of hypotension induced by arfonad in neurosurgery].

PMID- 15444984
TI  - [Diminution of local surface anesthetic activity of cocaine chloride in
      tuberculous rabbit].

PMID- 15444985
TI  - [Transportation of poliomyelitic patients with respiratory disorders].

PMID- 15444986
TI  - [Emerson bellows apparatus (bellows resuscitator); manual artificial respiration
      apparatus].

PMID- 15444987
TI  - [Extension piece for respiratory balloon].

PMID- 15444988
TI  - [The full-term, underdeveloped liveborn infant].

PMID- 15444989
TI  - [Infants born in the 6th month of pregnancy].

PMID- 15444990
TI  - [Fetal ascites with hydramnios; exceptional development towards recovery;
      critical review of the physiopathology of the amniotic fluid].

PMID- 15444991
TI  - [Relation of anesthesiologist to surgeon].

PMID- 15444992
TI  - [Indications for slow-acting or fast-acting curare in anesthesia for myasthenic
      patients].

PMID- 15444993
TI  - [Behavior of extracellular fluids in various types of general anesthesia].

PMID- 15444994
TI  - [Not Available].

PMID- 15444995
TI  - [Procaine block of pathways of visceral sensitivity in surgery].

PMID- 15444996
TI  - [d-2, 2-Diphenyl-3-methyl-4-morpholino-butyryl pyrrolidone (R 875): preliminary
      trials in surgery].

PMID- 15444998
TI  - [On surgical mortality and anesthetic risk].

PMID- 15444997
TI  - [Mechanism and prevention of peri-operative lethal accients].

PMID- 15444999
TI  - [Anesthesia risks].

PMID- 15445000
TI  - [Fatal peroperative complications in pediatric surgery].

PMID- 15445001
TI  - [Not Available].

PMID- 15445002
TI  - [The limits of preventing anaesthetic adverse effects in the post-operative
      period].

PMID- 15445004
TI  - [Not Available].

PMID- 15445003
TI  - [Plan for a joint study by surgeons and anesthesiologists on the anesthetic
      factor in operative mortality].

PMID- 15445005
TI  - [Myasthenia & slow-acting curare].

PMID- 15445006
TI  - [Terminal shock in intestinal occlusion treated with pendiomide].

PMID- 15445007
TI  - [Air embolism in a donor during the process of removing blood].

PMID- 15445008
TI  - [Prolonged apnea following succinylcholine; neostigmine therapy].

PMID- 15445009
TI  - [2 Respiratory accidents; treatment & recovery].

PMID- 15445010
TI  - [Physiopathology & treatment of cardiac arrest].

PMID- 15445011
TI  - [Neuromuscular excitability in anesthesia].

PMID- 15445012
TI  - [Local anesthetic activity of pramoxine hydrochloride (tronothane)].

PMID- 15445013
TI  - [Not Available].

PMID- 15445014
TI  - [Understanding the role of hypometabolism in organic protection].

PMID- 15445015
TI  - [Hypometabolism in neuroplegia].

PMID- 15445016
TI  - [Neuroplegic treatment of poliomyelitis].

PMID- 15445017
TI  - [One hundred cases of cardiovascular surgery accomplished under neuroplegia].

PMID- 15445018
TI  - [Choice of an artificial respiration procedure by external movements].

PMID- 15445019
TI  - [Advantages and difficulties of cardiorespiratory reanimation by pneumo
      insufflation at the place of a syncopal accident; presentation of a manual pneumo
      insufflator-exsufflator and a portable aspirator].

PMID- 15445020
TI  - [Possibility of electrocorticography under general anesthesia].

PMID- 15445021
TI  - [Value of blockage of the intercostal nerves in anesthesia].

PMID- 15445022
TI  - [Research on apparatus for the measurement of carbon dioxide by infrared method].

PMID- 15445023
TI  - [Organization and function of the Anesthesiology Center of the Surgical
      Therapeutic Clinic of Vaugirard].

PMID- 15445024
TI  - [Clinical use of acepromazine (CB-1522), plegicil)].

PMID- 15445025
TI  - [A new type of surgical anesthesia and the use in therapy of a depressor of the
      cerebral cortex (SCTZ)].

PMID- 15445026
TI  - [Hibernation in the dog with a view to right ventriculotomy in an exsanguinated
      heart].

PMID- 15445027
TI  - [Measurement of muscular excitability in surgical sequelae; diagnostic,
      prognostic & therapeutic value].

PMID- 15445028
TI  - [Structural analogies & synergy of analgesic action. III. Determination, after a
      mechanical stimulus, of the analgesic action of combinations of analgesics &
      various types of structural analogues endowed with spasmolytic properties].

PMID- 15445029
TI  - [Antagonistic action of glucose on procaine].

PMID- 15445030
TI  - [Experimental study of toxic reactions observed during hypotension induced by a
      thiophanium derivative].

PMID- 15445031
TI  - [General anesthesia in thyroidectomy].

PMID- 15445032
TI  - [Electroencephalographic manifestations of cerebral anoxia during cardiac
      surgery].

PMID- 15445033
TI  - [Steroid anesthesia in obstetrics; preliminary notes].

PMID- 15445034
TI  - [Particular indications for steroid anesthesia].

PMID- 15445035
TI  - [Problems posed by biliary surgery in coronary patients; preliminary note].

PMID- 15445036
TI  - [Not Available].

PMID- 15445037
TI  - [Problems of closed-mouth general anesthesia in maxillofacial surgery
      (bimaxillary blockage or temporomaxillary ankylosis)].

PMID- 15445038
TI  - [Indications & limitations of intravenous anesthesia in the child under two years
      of age].

PMID- 15445039
TI  - [Pharmacology of halogenated anesthetics].

PMID- 15445040
TI  - [VIII Congress of French Anesthesiology, Aix-en-Provence, 18-21 July 1957].

PMID- 15445041
TI  - [Artificial respiration: mechanical and anesthesia].

PMID- 15445042
TI  - [Initial anesthesiological trials with the intermittent adjustable respirator].

PMID- 15445043
TI  - [Not Available].

PMID- 15445044
TI  - [Plasma transfusion in some hemorrhagic syndromes].

PMID- 15445045
TI  - [Can one justifiably speak of substitutes for blood & blood derivatives in
      resuscitation].

PMID- 15445046
TI  - [Observations on several cases of the use of nor-adrenalin in resuscitation].

PMID- 15445047
TI  - [Procaine ganglion-block: intravenous procaine in massive doses as an
      antihemorrhage & antishock factor in chest surgery; study of 1000 cases].

PMID- 15445048
TI  - [Iron therapy as adjuvant in blood transfusion].

PMID- 15445049
TI  - [Anethocurarium: its place among muscle relaxants & its clinical importance].

PMID- 15445050
TI  - [Not Available].

PMID- 15445051
TI  - [Survey on the clinical results of curare-slmulants].

PMID- 15445052
TI  - [Not Available].

PMID- 15445053
TI  - [Action of muscle relaxants in thyroid surgery].

PMID- 15445054
TI  - [Various indications for controlled hypotension in cardiovascular surgery].

PMID- 15445055
TI  - [Not Available].

PMID- 15445056
TI  - [Role of pentamethonium in the prevention & treatment of surgical shock].

PMID- 15445057
TI  - [Study of blood eosinophil count in the surgery of infants].

PMID- 15445058
TI  - [Recent data on ganglion-blocking drugs].

PMID- 15445059
TI  - [Plasma substitutes].

PMID- 15445060
TI  - [Prolongation & reinforcement of narcosis under the influence of amines of 1
      bicyclohexyl-1-carboxylic acid esters & their iodomethylate derivatives].

PMID- 15445061
TI  - [Emergency transport of the asphyxiated by physicians of the Experimental
      Laboratory of Physical Medicine of the Public Assistance Administration of
      Paris].

PMID- 15445062
TI  - [The medical practitioner & the sport of diving].

PMID- 15445063
TI  - [Neuroplegia & artificial hibernation in critical conditions in seriously injured
      patients].

PMID- 15445064
TI  - [Potentiated anesthesia by acepromazine for cesarean section].

PMID- 15445065
TI  - [Preliminary report on the use of the maleate of acetylphenothiazine, CB-1522
      (plegicil) in artificial hibernation].

PMID- 15445066
TI  - [Trials with hydroxydione].

PMID- 15445067
TI  - [Succinylcholine (by perfusion) in general surgery].

PMID- 15445068
TI  - [Not Available].

PMID- 15445069
TI  - [Need of a first aid organization].

PMID- 15445070
TI  - [Traffic injuries & resuscitation].

PMID- 15445071
TI  - [Emergency treatment of electrocuted & industrial solvent-poisoned person].

PMID- 15445072
TI  - [Small scale experience of contemporary Algerian traumatology].

PMID- 15445073
TI  - [Intraosseous anesthesia in surgical operations on the limbs].

PMID- 15445074
TI  - [Hypotension-bradycardia syndrome under anesthesia & its treatment by
      sympathomimetics].

PMID- 15445075
TI  - [Emergency valvulotomy during subintrant crises of acute pulmonary edema treated
      by hexamethonium].

PMID- 15445076
TI  - [Respiratory depression due to hydroxydione].

PMID- 15445077
TI  - [Case of sever tetanus].

PMID- 15445078
TI  - [Presentation of universal rubber joints for masks, tubes & other adjutages
      utilizable in anesthesia & respiratory reanimation].

PMID- 15445079
TI  - [Artificial hibernation and autonomic nerve block. I. Ganglioplegic therapy
      during the campaign in Indochina from 1952-1954].

PMID- 15445080
TI  - [Intravenous therapy via the subclavian vein].

PMID- 15445081
TI  - [Influence of various enzymes on narcosis and on potentiated narcosis; their
      action on the duration of anesthesia and on cerebral metabolism during narcosis
      in vivo].

PMID- 15445082
TI  - [Deep hypothermia in brain surgery].

PMID- 15445083
TI  - [New methods of restoration of respiration in neurosurgery].

PMID- 15445084
TI  - [First results of clinical experimentation with R. 875 at the Regional Hospital
      Center at Montpellier].

PMID- 15445085
TI  - [Some comments following the anesthetic use of hydroxypregnandione succinate in
      more than 50 cases].

PMID- 15445086
TI  - [Comparison of the local anesthetic activity of procaine hydrochloride in normal
      and in tuberculous rabbits and guinea pigs].

PMID- 15445087
TI  - [Comparison of the local anesthetic activity of infiltrations of cocaine
      hydrochloride in tuberculous and in normal guinea pigs].

PMID- 15445088
TI  - [Local surface anesthetic activity of some higher organic acid salts of
      procaine].

PMID- 15445089
TI  - [Induction of anesthesia in children].

PMID- 15445090
TI  - [Value of the use of potassium lactate in reanimation].

PMID- 15445091
TI  - [Total prolonged arrest of cerebral circulation in artificial hibernation].

PMID- 15445092
TI  - [Artificial hibernation & autonomic ganglion blocking. II. Artificial hibernation
      in war surgery at various combat echelons].

PMID- 15445093
TI  - [N-allyl-normorphine (nalorphine): importance in surgical & medical
      anesthesiology; 59 personal case reports].

PMID- 15445094
TI  - [Current possibilities permitting the resolution of problems of anesthesia
      resuscitation in major neurosurgery; 200 case reports].

PMID- 15445095
TI  - [Premedication & anesthesia in children].

PMID- 15445096
TI  - [Direct high tension transthoracic defibrillation].

PMID- 15445097
TI  - [2 Short-acting intravenous anesthetics: cito-eunarcon & baytinal].

PMID- 15445098
TI  - [Combined anethocurarium & succinylcholine with curarizing action].

PMID- 15445099
TI  - [Preliminary note on the use of cocarboxylase in the surgical preparation of
      patients with poliomyelitic sequelae].

PMID- 15445100
TI  - [Surgical risk in aged over 75 years of age].

PMID- 15445101
TI  - [What is the concept of excitability?].

PMID- 15445102
TI  - [Combination of brevatonal & mediatonal in chest surgery; 978 case reports].

PMID- 15445103
TI  - [Deneau test: its use in study of diphenhydramine potentiation of acetylsalicylic
      acid].

PMID- 15445104
TI  - [Report on the AELSEM defibrillator; a standard method of defibrillation].

PMID- 15445106
TI  - [Organization of an anesthesiology service].

PMID- 15445105
TI  - [Ganglion-blocking in the treatment of paralytic ileus].

PMID- 15445107
TI  - [Artificial hibernation & autonomic block. III. Analytic study of the indications
      for artificial hibernation].

PMID- 15445108
TI  - [Effect of amino ether derivatives of phenols & alcohols on the duration of
      experimental sleep; relation of chemical structure to central action].

PMID- 15445109
TI  - [Limitations of barbiturate infusion in pediatric anesthesiology].

PMID- 15445110
TI  - [Preliminary note on the experimental study of various salts of DL-aspartic
      acid].

PMID- 15445111
TI  - [Significance of viadril in ORL; findings on 150 cases].

PMID- 15445112
TI  - [Treatment of autonomic disorders following injuries to the cervical cord].

PMID- 15445113
TI  - [Acute sodium fluoride poisoning].

PMID- 15445114
TI  - [Practical notions about a few problems of peri-operative nerve compression
      elongation].

PMID- 15445115
TI  - [Current aspects of anesthesia & resuscitation in military practice].

PMID- 15445116
TI  - [Resuscitation using glucose-insulinpotassium therapy in military surgery].

PMID- 15445117
TI  - [Intramuscular penthiobarbital in the prevention & treatment of delirium
      tremens].

PMID- 15445118
TI  - [Technic of study of changes of ionic equilibrium by transperitoneal or
      transcutaneous electrolytic polarization; preliminary study].

PMID- 15445119
TI  - [Artificial hibernation & neurovegetative ganglion blocking. III. Analytical
      study of indications for artificial hibernation].

PMID- 15445120
TI  - [Comparative study of various electrolytic balances after perfusion of surgical
      subtosan with & without sodium].

PMID- 15445121
TI  - [Human plasma substitutes].

PMID- 15445122
TI  - [Value of solutions of human serum albumin in reanimation].

PMID- 15445123
TI  - [Dextran with dextrose & without sodium (DDD)].

PMID- 15445124
TI  - [Artificial parenteral feeding of carbohydrates].

PMID- 15445125
TI  - [Variations in the blood sugar curve and the degree of assimilation of 30%
      hypertonic solutions of glucose administered by intravenous perfusion].

PMID- 15445126
TI  - [Anesthesia and reanimation in removal of obstructions and in grafting of the
      aortic bifurcation].

PMID- 15445127
TI  - [The limits of respiratory reanimation; the diagnosis of death of the central
      nervous system in comas with respiratory arrest].

PMID- 15445128
TI  - [Value of glucose and of sodium elimination in parenteral feeding in surgical
      patients].

PMID- 15445129
TI  - [Use of methitural (thiogenal) for ultrashort anesthesia].

PMID- 15445130
TI  - [New concepts on the metabolism of ammonia and its disorders].

PMID- 15445131
TI  - [Measurement of blood ammonia levels by diffusion].

PMID- 15445132
TI  - [Cutaneous congestion and erythema, warning signals of blood transfusion
      incompatibility in anesthetized patients].

PMID- 15445133
TI  - [Clinical trials with levomepromazine].

PMID- 15445134
TI  - [Two cases of prolonged apnea after succinylcholine administration].

PMID- 15445135
TI  - [Biological study of perfusions with the potassium and magnesium salts of
      aspartic acid in clinical practice].

PMID- 15445136
TI  - [Variations in blood ammonia levels induced by the injection of ammonium chloride
      in rabbits].

PMID- 15445137
TI  - [Variations in the ammonia level of preserved blood in the presence of aspartic
      acid salts and ATP].

PMID- 15445138
TI  - [Induction of hypothermia by the gastric route].

PMID- 15445139
TI  - [Method of use and indications for fluothane; report on 150 cases].

PMID- 15445140
TI  - Bacterial endotoxins and the radiation syndrome.

PMID- 15445141
TI  - Strontium-90 on the earth's surface. Summary and interpretation of a world-wide
      soil sampling program.

PMID- 15445142
TI  - [Considerations on excessive fetal weight].

PMID- 15445143
TI  - [Geriatric gynecological surgery, Clinicostatistical study].

PMID- 15445144
TI  - [Prognosis of the newborn from cesarean section].

PMID- 15445145
TI  - [On a case of simultaneous presence of primary cancer of the uterus and of
      primary cancer of the ovary with metastases to the uterus through the fallopian
      tube].

PMID- 15445146
TI  - Cytological observations of the male reproductive organs of the mouse and dog
      following administration of deuterium oxide.

PMID- 15445147
TI  - Urinary taurine excretion and the partition of sulfur in four species of mammals
      after whole body x-irradition.

PMID- 15445148
TI  - [Anesthesia in geriatric gynecological surgery. (Clinico-statistical study of the
      past decade)].

PMID- 15445149
TI  - [Local use of corticosteroids in the therapy of vulvar pruritus].

PMID- 15445150
TI  - Illinois bone tumor death certificate study.

PMID- 15445151
TI  - [Contribution to the study of the mechanism of action of relaxin on the
      myometrium of the gravid rat. (Experiments with P-32 radioactive phosphorus)].

PMID- 15445152
TI  - [Lumbar peridural anesthesia in cesarean section].

PMID- 15445153
TI  - Studies on the establishment and growth of tumor metastases using tritiated
      thymidine.

PMID- 15445154
TI  - [Trypsin-chymotrypsin therapy in female genital inflammations].

PMID- 15445155
TI  - Some physiological changes observed in human subjects during zero G simulation by
      immersion in water up to neck level.

PMID- 15445156
TI  - [On the subject of induced labor: the Krause method in the light of modern
      trends].

PMID- 15445157
TI  - [Adaptation of the Tzanck apparatus for exchange transfusion].

PMID- 15445158
TI  - [Etiopathogenetic considerations on neonatal hemolytic disease (N.H.D.) with
      special reference to Rh factors].

PMID- 15445159
TI  - [Immunohematological study of the unit for prevention of neonatal hemolytic
      disease (N.H.D) at the Ospedale di Varese].

PMID- 15445160
TI  - [Rapid method for differentiating fetal blood from maternal blood at the time of
      birth in immunological investigations].

PMID- 15445161
TI  - [The prediction of hemolytic disease of the newborn].

PMID- 15445162
TI  - Effects of protein depletion on the lethality of whole or partial body x
      irradiation of the rat.

PMID- 15445163
TI  - [Observations and considerations of tranquilizing agents in obstetrics and
      gynecology].

PMID- 15445164
TI  - [Clinical and anaomopatno logical considerations on a case of granulosa cell
      tumor].

PMID- 15445165
TI  - [Morphological abnormalities of the placenta. (On a case of unusual anomaly)].

PMID- 15445166
TI  - [Anatomo-physiology of the adrenal cortex in pregnancy].

PMID- 15445167
TI  - [Anatomo-physiology of the adrenal cortex in pregnancy].

PMID- 15445168
TI  - [Asthenia and myasthenia in pregnancy].

PMID- 15445169
TI  - [Controlled diet and climateric obesity].

PMID- 15445170
TI  - [Current knowledge concerning the clinical use of the more recent synthetic
      progestative agents].

PMID- 15445171
TI  - [Effect of a pharmacological combination in the therapy of pregnancy toxemia].

PMID- 15445172
TI  - [Importance of angiotrophic factors in the prevention and therapy of abortion].

PMID- 15445173
TI  - [Observations on cholecysto-cholangiopathic syndromes in the premenopause].

PMID- 15445174
TI  - [Observations on the use of a soluble derivative of tetracycline by
      endoperitoneal and intramuscular route].

PMID- 15445175
TI  - [On the treatment of amenorrhea with drugs of the neurovegetative system].

PMID- 15445176
TI  - [On the use of the molecular combination of trypsin and heparin in thromboembolic
      manifestations of obstetrical and gynecological origin].

PMID- 15445177
TI  - [Physiopathology of the puerperium (Part 2:Pathology)].

PMID- 15445178
TI  - [Placenta and enzymes].

PMID- 15445179
TI  - [The placenta. I. Placentation in mammals].

PMID- 15445180
TI  - [The placenta].

PMID- 15445181
TI  - Photoperiodic investigations. I. Variability in flowering of xanthium near
      critical day lengths.

PMID- 15445182
TI  - [Morphologic and functional aspects of the adrenal cortex in relation to ovarian
      function].

PMID- 15445183
TI  - [Research and considerations on various cases of prediabetes in pregnancy].

PMID- 15445184
TI  - [Some investigations on adrenal cortex function in gestosis].

PMID- 15445185
TI  - [Study of the metabolism of estrone on thyroparathyroidectomized animals].

PMID- 15445186
TI  - Gravity problems in manned space stations.

PMID- 15445187
TI  - Some body displacements and medical effects of lateral accelerations during Navy
      centrifuge simulation of ejection capabilities from the Army AO aircraft.

PMID- 15445188
TI  - Studies of the action of mercuric chloride on intestinal absorption.

PMID- 15445189
TI  - A method for the computation of aortic distensibility in the living human
      patient.

PMID- 15445190
TI  - [On the favorable results obtained with a new orally active progestin
      (cyclopentylenolic ether of 17 alpha-acetoxyprogesterone) in the therapy of
      threatened abortion].

PMID- 15445191
TI  - Electrical analog simulation of temperature regulation in man.

PMID- 15445192
TI  - [The importance of alkaline phosphatases in glucide metabolism of the human
      placenta. Histochemical considerations in various stages of placental
      development].

PMID- 15445194
TI  - Attempts at enzymatic induction of E. coli.

PMID- 15445193
TI  - [The basal thermal curve in threatened abortion and in the prognosis of the
      appearance of labor].

PMID- 15445195
TI  - Adaptation of Benson-Lehner data reduction equipment for x-ray diffraction film
      measurement.

PMID- 15445196
TI  - X-ray diffraction studies of cytosine, uracil and thymine.

PMID- 15445197
TI  - [Introduction to the study of relapse and recurrence in pulmonary tuberculosis].

PMID- 15445198
TI  - Studies on the effects of deuterium oxide. VIII. The effect of deuterium on the
      reproductive potential of male mice.

PMID- 15445199
TI  - Latency and growth of osteosarcomas induced by radiostrontium.

PMID- 15445200
TI  - Radium damage in mouse bone.

PMID- 15445201
TI  - Progress report: diseases of laboratory animals. Ectromelia infection of mice.

PMID- 15445202
TI  - Progress report: diseases of laboratory animals. Pseudomonas infection of mice.

PMID- 15445203
TI  - Progress report: thorium removal.

PMID- 15445204
TI  - Lewis salts for use in organometallic syntheses.

PMID- 15445206
TI  - Missile studies with a biological target.

PMID- 15445205
TI  - [Menstruation and conception during breast feeding].

PMID- 15445207
TI  - Practical management of pruritus ani.

PMID- 15445208
TI  - Cortisone and infection.

PMID- 15445209
TI  - Reduction in elevated blood cholesterol levels with lipomic injection.

PMID- 15445211
TI  - Treatment of ocular disease and injury by the general practitioner.

PMID- 15445210
TI  - Improved apparatus for measurement of the cosmicray neutron background.

PMID- 15445212
TI  - Gamma-ray studies on radioactive fallout in soil.

PMID- 15445213
TI  - Fallout transport as deduced from measurement of gamma-emitting radioactivity in
      air.

PMID- 15445214
TI  - Air cleaning practice at U.K.A.E.A., Aldermaston.

PMID- 15445215
TI  - T e biolocial effects of upper body x-irradiation of beagles.

PMID- 15445216
TI  - Standard-man phantoms.

PMID- 15445217
TI  - A guide to the management of placenta praevia.

PMID- 15445218
TI  - A displacement-sensing constant-torque response lever designed for use in
      satellites.

PMID- 15445219
TI  - Accuracy of lever-displacement behavior of rats following exposure to positive
      accelerations.

PMID- 15445220
TI  - Summary of air cleaning activities at Atomics International.

PMID- 15445221
TI  - Effects of anoxia on the formation of dendrites in the developing cerebral
      cortex.

PMID- 15445222
TI  - How to design and build abnormal brains using radiation during development.

PMID- 15445223
TI  - Malformation and regeneration of the mammalian retina following experimental
      radiation.

PMID- 15445224
TI  - The effects of ionizing radiations on the developing animal with special
      reference to the nervous system.

PMID- 15445225
TI  - Effects of irradiation on the calcifying mechanism of epiphyseal cartilage.

PMID- 15445226
TI  - Analysis of tissue samples for polonium-210 (RaF).

PMID- 15445227
TI  - Critique on the half-lives of lead and RaD in the human body.

PMID- 15445228
TI  - Some determinations of the RaD and RaF concentrations in human bone.

PMID- 15445229
TI  - The RaD content of some potable waters in Illinois.

PMID- 15445230
TI  - The distribution of the RaD concentration as a function of bone type in three
      unexposed subjects.

PMID- 15445231
TI  - The effect of oxygen tension on the radiosensitivity of the chick embryo.

PMID- 15445232
TI  - Suggested RCG values for radioiodine isotopes in foods.

PMID- 15445233
TI  - Deanol as aid in overcoming reading retardation.

PMID- 15445234
TI  - Radium in bone and soft tissues of man.

PMID- 15445235
TI  - Cessation of shivering following forebrain lesions in anesthetized cats.

PMID- 15445236
TI  - Estimates of accumulated exposures and environmental build-up of radioactivity.

PMID- 15445237
TI  - A clinical study with glyceryl triacetate.

PMID- 15445238
TI  - Infective organisms living in the cytoplasm of Amoeba proteus.

PMID- 15445239
TI  - X-irradiation of the giant amoeba, Pelomyxa illinoisensis. III. Election
      microscopy of centrifuged organisms.

PMID- 15445240
TI  - Microinjection studies on amoebae after their exposure to a supralethal dose of x
      rays or gamma-rays.

PMID- 15445242
TI  - Shipping and storage of radioactive materials.

PMID- 15445241
TI  - The effects of ionizing radiations on peripheral nerve. II. Alteration of
      resting, action and local potentials of cravfish giant axons by UV irradiation.

PMID- 15445243
TI  - The retention of strontium-85 in the dog.

PMID- 15445245
TI  - [Treatment of chronic cor pulmonale].

PMID- 15445244
TI  - Special incineration studies -- institutional design.

PMID- 15445246
TI  - Ra-226 in bovine bones and teeth.

PMID- 15445248
TI  - The T-Sonde, a low level air temperature measuring device.

PMID- 15445247
TI  - Filter efficiency studies at Goodyear Atomic Corporation.

PMID- 15445249
TI  - [Modern electrodiagnosis for the clinic and for practice].

PMID- 15445250
TI  - The effects of ionizing radiations on peripheral nerve. I. The effects of in situ
      x-irradiation on mammalian nerve action potential.

PMID- 15445251
TI  - Waste calciner off-gas system.

PMID- 15445252
TI  - Importance of early diagnosis and treatment of gastric carcinoma.

PMID- 15445253
TI  - Summary of air cleaning activities at Chalk River.

PMID- 15445255
TI  - The effects of chronic gamma irradiation on mouse testis.

PMID- 15445254
TI  - A note on the statistical determination of shape of chromatic elements in cross
      sections of nuclear material in human sperm.

PMID- 15445256
TI  - The effects of parathyroid hormone on phosphate transport.

PMID- 15445257
TI  - Eczema treatment.

PMID- 15445259
TI  - Experience with non-filtered air systems at the Idaho Test Station.

PMID- 15445258
TI  - Summary of present trials of anticancer agents.

PMID- 15445260
TI  - Ventilation systems at Atomics International.

PMID- 15445261
TI  - Biological effects of nuclear radiation on the monkey (Macaca mulatta): two-year
      evaluation.

PMID- 15445262
TI  - Probability of ionization in energy transfer from excited atoms to molecules.

PMID- 15445263
TI  - Teaching in a rural hospital.

PMID- 15445264
TI  - Phenformin: fifty-four month experience.

PMID- 15445265
TI  - Air cleaning at the Knolls Atomic Power Laboratory.

PMID- 15445266
TI  - Emergency treatment of bleeding esophageal varices.

PMID- 15445267
TI  - The doctor and his federal income tax.

PMID- 15445268
TI  - Damage to conventional and special types of residences exposed to nuclear
      effects.

PMID- 15445269
TI  - Environmental beta-gamma radio activity in air at Sandia Laboratory First Quarter
      1960.

PMID- 15445270
TI  - Environmental beta-gamma radio activity in air at Sandia Laboratory Second
      Quarter 1960.

PMID- 15445271
TI  - Comparison of fallout doses from Nevada tests (revised).

PMID- 15445272
TI  - The effect of ageing on the G-tolerance of rats.

PMID- 15445273
TI  - The effect of acclimatization to cold on the G tolerance of rats.

PMID- 15445274
TI  - The adsorption of volatile ruthenium on silica gel.

PMID- 15445275
TI  - The installation, handling and storage of high efficiency filters.

PMID- 15445276
TI  - The internal environment of underground structures subject to nuclear blast. 2.
      Effects on mice located in heavy concrete shelters.

PMID- 15445277
TI  - Progress report: relationship of plutonium removal to tumor incidence. I.
      Experimental design and preliminary results.

PMID- 15445278
TI  - Nuclear structures observed during division in the giant amoebae.

PMID- 15445279
TI  - The use of methacrylate membranes to protect thin sections from damage during
      electron microscopy.

PMID- 15445280
TI  - The cell membrane as the site of action of heavy metals.

PMID- 15445281
TI  - Bone studies on an exhumed radium patient.

PMID- 15445282
TI  - Microscopic metabolism of Ra-226 in canine bone. II.

PMID- 15445283
TI  - Plugged haversian canals in a radium case.

PMID- 15445284
TI  - The use of iodine as an indicator for reactor monitoring.

PMID- 15445285
TI  - Survival of guinea pigs under duration-of-life exposure to gamma rays.

PMID- 15445286
TI  - Progress report: dynamics of cellular populations.

PMID- 15445287
TI  - Clinical study of trichlormethiazide, an oral diuretic agent.

PMID- 15445288
TI  - Experiments on the biosynthesis of azetidine-2-carboxylic acid in Convallaria
      majalis.

PMID- 15445289
TI  - Progress report: plutonium removal. IV. Tissue distribution of monomeric and
      polymeric plutonium as modified by a chelating agent.

PMID- 15445290
TI  - Disposition of nuclear fallout debris. Annual report.

PMID- 15445291
TI  - The cause and nature of an aplastic anemia of the bovine and its relation to
      radiation pancytopenia.

PMID- 15445292
TI  - Studies on chemical protection against radiation-induced intestinal injury.

PMID- 15445293
TI  - Venous anatomy of the lower extremity.

PMID- 15445294
TI  - [Therapeutic possibilities of progestational substances in uterine myomatosis].

PMID- 15445295
TI  - [Production of a dosimetric device for the registration of beta-activity within
      body cavities in oncological practice].

PMID- 15445296
TI  - [Role of early general reactions of the maternal organism in the mechanism of
      fetal injury by ionizing radiations].

PMID- 15445297
TI  - [On the incidence of liver damage after gastrectomy].

PMID- 15445298
TI  - [Heart arrest after injections of 125 milligrams of Ajmaline].

PMID- 15445299
TI  - [On the nature of the interrelationships between the blood pressure, tone of the
      blood vessels and body temperature in white rats during radiation injury].

PMID- 15445300
TI  - [Conditions of adrenocortical function under the influence of chronic ionizing
      irradiation].

PMID- 15445301
TI  - [Is primary surgical treatment of malignant melanoma still recommended today?].

PMID- 15445302
TI  - [On a laboratory Leptospira ballum infection; orchitis as a complication].

PMID- 15445303
TI  - [On the delayed form of development of acute carbon monoxide poisoning].

PMID- 15445304
TI  - [On the analysis of the fibrinolytic system in occlusive arterial disease].

PMID- 15445305
TI  - [Artificial feeding].

PMID- 15445306
TI  - [Changes in the endocrine system under the influence of radiations].

PMID- 15445307
TI  - [On the therapeutic effect of Hinokitiol on decubitus ulcers].

PMID- 15445308
TI  - Efficacy of a combined hydrosorbent and anticholinergic in treating diarrheas
      from varied causes.

PMID- 15445309
TI  - [Phonocardiography of heart sounds].

PMID- 15445310
TI  - [A contribution to the scope of indication for complamine therapy].

PMID- 15445311
TI  - [Effect of screening and of the administration of bone marrow cells on the
      effectiveness of seroprophylaxis of diphtherial intoxication in irradiated
      animals].

PMID- 15445312
TI  - [Seroreactions in the diagnosis and activity control of rheumatic diseases].

PMID- 15445313
TI  - [Absence of renal changes after coli bacillus injections in rabbits chronically
      treated with phenacetin].

PMID- 15445314
TI  - ["Tuberculosis in the aged" and the general practitioner].

PMID- 15445315
TI  - [Permanent brain injuries following traffic accidents].

PMID- 15445316
TI  - [Comparative studies on determination of gastric acidity with the gastracid test
      and fractionated removal of the gastric contents].

PMID- 15445317
TI  - [The problem of the virus etiology of cancer].

PMID- 15445318
TI  - [Radiotherapy of malignant tumors of the mediastinum].

PMID- 15445319
TI  - [Roentgenotherapy of malignant tumors of the mediastinum with the aid of a lead
      grid].

PMID- 15445320
TI  - [Experiences in genetal practice with immunocillin].

PMID- 15445321
TI  - [Role of a depot substance on Clostridium perfringens antitoxin production in the
      condition of total body irradiation].

PMID- 15445322
TI  - [Use of thymidine labeled with tritium in the determination of bone marrow cell
      viability].

PMID- 15445323
TI  - [Traumatic spleen-pancreas cystoid].

PMID- 15445324
TI  - [Protective effect against radiation sickness by native sera of irradiated
      animals].

PMID- 15445325
TI  - [A contribution to the problem of cerebral angiospastic insult].

PMID- 15445326
TI  - [On the clinical aspects and prognosis of genital tuberculosis].

PMID- 15445327
TI  - [On the subject of disease and environment].

PMID- 15445328
TI  - [Incorporation and de-corporation of radioisotopes].

PMID- 15445329
TI  - [Experiences with Megaphen compositum in psychiatry].

PMID- 15445330
TI  - Comparison of oral drugs in treatment of itching dermatoses.

PMID- 15445331
TI  - [Nonspecific irritant therapy of degenerative rheumatism].

PMID- 15445333
TI  - [Some current problems of dosimetry in clinical radiology].

PMID- 15445332
TI  - [On the conservative treatment of arterial embolism].

PMID- 15445335
TI  - [Practical colposcopy. II].

PMID- 15445334
TI  - [Pruritus and antiprurinigous agents].

PMID- 15445336
TI  - [Practical colposcopy].

PMID- 15445337
TI  - [Practical colposcopy. I].

PMID- 15445338
TI  - [Clinical experiences with the 2 phase anticonvulsant 244 H in epileptis
      committed to asylums].

PMID- 15445339
TI  - [Result of pathophysiological and clinical evaluation of changes in erythrocyte
      resistance to saponin during the process of roentgenotherapy].

PMID- 15445340
TI  - Loss of mutagenic potential in bacteria.

PMID- 15445341
TI  - The cell generation rate distribution.

PMID- 15445342
TI  - [Shock and anuria after radium-roentgen irradiation of a myomatous uterus].

PMID- 15445343
TI  - [Basal metabolism and morphological composition of the peripheral blood during
      radioactive iodine therapy of thyrotoxicosis].

PMID- 15445345
TI  - [Aimed therapy of chronic recurrent pancreatitis].

PMID- 15445344
TI  - [Menstruation anomalies in extrauterine pregnancy].

PMID- 15445346
TI  - [Development of a left bundle-branch block in myotonic dystrophy].

PMID- 15445347
TI  - [Appendicitis and Head's zones].

PMID- 15445348
TI  - [Results of a symposium on cranial rheography].

PMID- 15445349
TI  - [On the effect of radioactive iodine on the thyroid gland, pituitary and adrenals
      in rabbits].

PMID- 15445350
TI  - [Bibliographic sources of medical radiology].

PMID- 15445351
TI  - [Bibliographical sources of medical radiology].

PMID- 15445352
TI  - [Peripheral resistance and minute volume of the blood in acute radiation
      sickness].

PMID- 15445353
TI  - [Basic factors in the environment and occupational hazards occurring on
      accelerators of mono-and multichargedions].

PMID- 15445354
TI  - [Characteristics of the course of acute radiation sickness in young rats].

PMID- 15445355
TI  - [Some details concerning the equipment of glove boxes].

PMID- 15445356
TI  - [Clinical and experiemntal research on the use of demethylchlortetracycline in
      pediatrics].

PMID- 15445358
TI  - The bacterial cell wall.

PMID- 15445357
TI  - [Generalized cytomegaly in uniovular twins].

PMID- 15445359
TI  - Tetracycline: correlation of clinical results and in vitro bacterial
      susceptibility.

PMID- 15445360
TI  - [On high-dosage pyramidon treatment of acute encephalitis in childhood].

PMID- 15445361
TI  - [The therapy of hemorrhoids with a new hemorrhoidal therapeutic agent].

PMID- 15445362
TI  - [A suicide attempt with tofranil in combination with sedatives].

PMID- 15445363
TI  - [Vegetative dystonia from the viewpoint of endocrinology].

PMID- 15445364
TI  - [Prevention of radiation sickness in mother and fetus in utero].

PMID- 15445366
TI  - [Functional and morphological changes in the lymphatic system in secondary
      chronic radiation sickness].

PMID- 15445365
TI  - [On detoxication disorders of the organism in radiation sickness].

PMID- 15445367
TI  - [The topical use of dexamethasone in the orthopedic practice].

PMID- 15445368
TI  - [Diseases of the mesencephalon].

PMID- 15445369
TI  - [On the psychopathology of the various brain segments (with the exception of the
      forebrain and midbrain)].

PMID- 15445370
TI  - [On the demonstration of the effects of an antitussive agent in the treatment of
      bronchospastic phenomena].

PMID- 15445371
TI  - [Is a single determination of antistreptolysin titer as a focal test in chronic
      tonsillitis suitable?].

PMID- 15445372
TI  - [Blood circulation studies on the effect of niamide].

PMID- 15445373
TI  - Intransigencies in the study of cholesterol ester metabolism.

PMID- 15445374
TI  - [Comments on the article of V. M. Mastriukova, "Lymph Circulation Changes after
      Local Large-Dose Ionizing Irradiation"].

PMID- 15445375
TI  - [Psychodiagnostic objectification of therapeutic results in complaints in old
      age].

PMID- 15445376
TI  - [Pharmacological diagnosis in bronchial asthma].

PMID- 15445377
TI  - [On the mechanism of protective effects of organ screening in total-body
      irradiation of rats].

PMID- 15445378
TI  - [The information character of modern ballistography].

PMID- 15445379
TI  - [The statement of the 5th International Pugwash Conference, concerning biological
      and chemical warfare].

PMID- 15445380
TI  - [Vascular reactions of internal organs to the administration of adrenalin in
      rabbits after total-body irradiation].

PMID- 15445381
TI  - [New experiences in the treatment of E. coli dyspepsia in infants].

PMID- 15445382
TI  - [Noteworthy success in chemotherapy of a metastasizing malignancy of the
      abdominal cavity].

PMID- 15445383
TI  - [On the therapy of infectious acute intstinal diseases including cholera].

PMID- 15445384
TI  - [Determination of Sr90 and Ca45 simultaneously present in biological substrates].

PMID- 15445385
TI  - [Physical models for rheography].

PMID- 15445386
TI  - [Treatment of tapeworm with Yomesan in 36 patients].

PMID- 15445387
TI  - [Antibiotics in the feeding of domestic animals and their effect on man].

PMID- 15445388
TI  - [Amplification of cranial rheographic diagnosis through registration in the
      extreme respiration phases].

PMID- 15445389
TI  - [On the pathogenesis, clinical aspects and differential diagnosis of symptomatic
      aplastic forms of anemia with a final picture of leukosis].

PMID- 15445391
TI  - [Mononucleosis infectiosa].

PMID- 15445390
TI  - [A-O and B-O blood group incompatibility in children of the same mother].

PMID- 15445392
TI  - [Neurotropic virus diseases. I].

PMID- 15445393
TI  - [Modern electrotherapy including electric healing-sleep].

PMID- 15445394
TI  - [Treatment of postoperative parotitis with novocaine infiltration of the stellate
      ganglion].

PMID- 15445395
TI  - [Research with endoxan therapy of tumors in children].

PMID- 15445396
TI  - [Lateral blood pressure differences of the upper extremities].

PMID- 15445397
TI  - [The effects of new diuretics on the electrolyte balance, the aldosterone
      excretion and the behavior of the thromboelastogram in normal persons].

PMID- 15445398
TI  - [Fibrinolysis].

PMID- 15445399
TI  - [A survey of 5700 percutaneous kidney biopsies].

PMID- 15445400
TI  - [On the features of the functional recovery of the hematopoietic system in dogs
      after burns complicated by ionizing radiation].

PMID- 15445401
TI  - [Histological manifestations of certain changes in tissue proteins].

PMID- 15445402
TI  - [Some results and prospects of scientific research in the field of clinical
      radiology].

PMID- 15445403
TI  - [Changes in the blood coagulation system in acute radiation sickness].

PMID- 15445404
TI  - [Confuso-oneiric manifestations in the course of thymoleptic treatment].

PMID- 15445405
TI  - Evaluation of prednisolone tertiary-butylacetate with propoxycaine in treatment
      of orthopedic disorders.

PMID- 15445406
TI  - [Radiation-induced occurrences in the organism].

PMID- 15445407
TI  - [Arterial pressure changes in rabbits in relation to radiation doses].

PMID- 15445408
TI  - [Observations on a case of carcinoid syndrome. Anti-serotonin treatment after
      resection of the small intestine].

PMID- 15445409
TI  - High dosages of hydroxyzine in treatment of institutionalized mental patients.

PMID- 15445410
TI  - [The feature of the process of blood regeneration in remote periods following
      injury to the organism by Sr-90 and x-rays].

PMID- 15445411
TI  - [Chronic effects of small doses of roentgen rays on offspring of dogs receiving
      uranium fission products].

PMID- 15445412
TI  - [On the problem of the prevention of biligraffin injurious effects].

PMID- 15445413
TI  - [Pneumonia in rats caused by cooling 3 months after roentgen irradiation].

PMID- 15445414
TI  - [Hip-joint mechanism in learning to walk. Improvement through hip erection and
      adapted crutch support in poliomvelitis patients].

PMID- 15445415
TI  - The inhalation toxicity of indium sesquioxide in the rat.

PMID- 15445416
TI  - [Skin reaction to beta-radiations during the use of applicators with radioactive
      phosphorus].

PMID- 15445417
TI  - [Gamma therapy of malignant tumors of the pharynx with radioactive cobalt].

PMID- 15445418
TI  - [Changes in the functional state of the hypophysis under the influence of the
      action of ionizing radiations].

PMID- 15445419
TI  - [The effect of ionizing radiations on the vegetative nervous system].

PMID- 15445420
TI  - [A new method for the registration of intracranial circulatory changes].

PMID- 15445421
TI  - [Clinical study of a new agent anabolizing protein].

PMID- 15445422
TI  - [Experimental animal and histological results in fracture gluing with the
      polyurethane polymer "ostamer"].

PMID- 15445423
TI  - [Effect of total-body gamma-irradiation on hormonal activity of the adrenal
      cortex].

PMID- 15445424
TI  - [The effect of various anticholinesterase preparations on the course and outcome
      of radiation injuries].

PMID- 15445425
TI  - [Congenital disorders with abnormal chromosomal numbers].

PMID- 15445426
TI  - [Congenital disorders with abnormal chromosome count].

PMID- 15445427
TI  - [Experience with strychnine in the prevention of radiation sickness during
      radiotherapy].

PMID- 15445428
TI  - The total tumor incidence in LAF" mice exposed to chronic gamma irradiation.

PMID- 15445429
TI  - [The use of telegamma-therapy in malignant tumors of the bone].

PMID- 15445430
TI  - [Experimental analysis of the state of the thyroid gland in chronic generalized
      irradiation].

PMID- 15445431
TI  - Diagnosis and management of intestinal obstruction.

PMID- 15445432
TI  - Minor surgical procedures with mepivacaine for local anesthesia.

PMID- 15445433
TI  - [SU-4885 (Metopiron)-test for determination of hypophysial-adrenal reserve].

PMID- 15445434
TI  - [The importance of ACTH in the pathogenesis of Cushing's disease].

PMID- 15445435
TI  - Factors influencing the biological fate and persistence of radioactive fall-out.

PMID- 15445436
TI  - [A guide to literature on problems of teaching medical radiology].

PMID- 15445437
TI  - [Features of the course of exudative pleurisy during the action of radiations
      (experimental study)].

PMID- 15445438
TI  - Diagnosis and treatment of secondary amenorrhea.

PMID- 15445439
TI  - [Immediate results of treatment of sarcoma of the vagina in dogs with the use of
      betatron].

PMID- 15445440
TI  - Treatment of acne vulgaris with a formulation containing aluminum chlorhydroxy
      allantoinate.

PMID- 15445441
TI  - Correlation of the natural radioactivity of the human body to that of its
      environment: uptake and retention of Ra226 from food and water.

PMID- 15445442
TI  - [Reticulm cell sarcoma of the humerus with spontaneous fracture in chronic
      myeloid leukemia].

PMID- 15445444
TI  - [Right insufficiency of the heart. Short review on the etiology and clinical
      aspects of right insufficiency with special reference to simple diagnosis].

PMID- 15445443
TI  - [On the differential diagnosis of brief duration unconsciousness. Pressure
      postpressure syncope].

PMID- 15445446
TI  - [Electrophysiological hypotheses of electrodiagnosis and electrotherapy].

PMID- 15445445
TI  - [Treatment of chronic eczemas and neurodermatitis with Sr90].

PMID- 15445447
TI  - [Clinical differential diagnosis of arterial insufficiency and orthopedic
      diseases of the lower extremities].

PMID- 15445448
TI  - [On changes in the nervous apparatus of the thyroid gland following
      administration of I-131 into the animal organism].

PMID- 15445449
TI  - [Delimitations and pathogenesis of clinically significant dysproteinemias].

PMID- 15445450
TI  - [On the correlation between leukocyte-and serum protein content in the blood of
      patients with chronic inflammatory diseases].

PMID- 15445451
TI  - [New findings on the diagnosis and therapy of pernicious anemia].

PMID- 15445452
TI  - [On a bioptically determined basophilic degeneration of the myocardial fibrils in
      a 33-year-old patient with mitral stenosis].

PMID- 15445453
TI  - [Certain problems of hygienic standardization of the maximum permissible doses of
      ionizing radiations].

PMID- 15445454
TI  - Radioactive hotspots, bone growth and bone cancer. Self-burial of calcium-like
      hotspots.

PMID- 15445455
TI  - [Snapping wrist and carpal tunnel syndrome].

PMID- 15445456
TI  - [Will the secular growth of the children of Geneva come to an end?].

PMID- 15445457
TI  - [The current status of therapy of metastasizing breast carcinoma].

PMID- 15445458
TI  - The obvious in obesity.

PMID- 15445459
TI  - [Comparative controls of substances belonging to the phenothiazine group in local
      anesthesia].

PMID- 15445460
TI  - [The effect of P32 application on the content of glucose and water in the blood
      and skin of rabbits].

PMID- 15445461
TI  - [Experimental rheographic research on a model].

PMID- 15445463
TI  - Angular response of scintillation detectors.

PMID- 15445462
TI  - [Study of the thromboplastic action of various phospholipids with the aid of
      suspensions of radioactive phosphatidyl-ethanol-amines].

PMID- 15445464
TI  - [On the steroid therapy of common hirsutism].

PMID- 15445465
TI  - [Advances in research and treatment of plague].

PMID- 15445466
TI  - Late manifestations of ionizing radiation in the dog.

PMID- 15445467
TI  - Cardiopulmonary changes in the dog following exposure to x-rays.

PMID- 15445468
TI  - [A new incidence of herediatary double albuminemia].

PMID- 15445469
TI  - [Further experimental animal research on the problem of the pathogenesis of
      interstitial nephritis].

PMID- 15445470
TI  - [Role of magnesium compounds in experimental radiation sickness].

PMID- 15445471
TI  - [The relationship between the dosage value of antenatal radiation and the state
      of higher nervous activity in adult animals].

PMID- 15445472
TI  - [Remote results of Po-210 injury].

PMID- 15445473
TI  - [The effect of local and generalized x-ray on the anterior portion of the eye].

PMID- 15445474
TI  - Cesium-137 potassium-40 ratios in eight control subjects over a span of 30
      months.

PMID- 15445475
TI  - Measurement of K42 in humans.

PMID- 15445476
TI  - Intra-articular injections of triaMCInolone acetonide in arthritic conditions.

PMID- 15445477
TI  - Triclobisonium chloride in dermatologic office practice.

PMID- 15445478
TI  - [A case of retarded growth of the bones of the forearm in a girl after
      radiotherapy of hemangioma of the skin].

PMID- 15445479
TI  - [Condition of the lymphatic system under the influence of acute effect of
      ionizing radiations according to data obtained by intravital lymphography].

PMID- 15445480
TI  - [The status of the lymphatic pathways in acute radiation injury according to data
      of intravital lymphography].

PMID- 15445481
TI  - [Treatment of idiopathic sprue (4 cases) by means of parenteral corticosteroid
      therapy (prednisolone, dexamethasone)].

PMID- 15445482
TI  - [Progress in hematology].

PMID- 15445483
TI  - [Pseudoaplastic anemia (malignant reticuloses or aleukemic lymphadenoses) and
      their therapy].

PMID- 15445484
TI  - [The present treatment of hypertension in general practice].

PMID- 15445486
TI  - [Some problems in the clinical picture of experimental radiation sickness].

PMID- 15445485
TI  - [Sanitary-hygienic requirements and standards of new sanitary laws regulating
      work with radioactive substances and sources of ionizing radiations].

PMID- 15445487
TI  - [Regulation of conscious and sleeping states as a physiological problem].

PMID- 15445488
TI  - Cell renewal in leukemic states in man: a preliminary report.

PMID- 15445489
TI  - [Listeriosis. An additional observation on granulomatosis infantiseptica in
      Switzerland].

PMID- 15445490
TI  - The effect of inhaled radon on the survival, body weight and hemogram of the
      mouse following single exposures.

PMID- 15445491
TI  - A linear scanner for human radioisotope research.

PMID- 15445492
TI  - [Aneurysmal ruptures of the abdominal aorta. Possibilities of emergency surgical
      treatment].

PMID- 15445493
TI  - [The activity of Te-127 and Te-129 in the animal organism].

PMID- 15445494
TI  - [A bichamber betatron for medicinal use].

PMID- 15445495
TI  - [Phosphorus and prophylaxis of caries].

PMID- 15445496
TI  - [Papillary giant follicular thyroid gland adenoma of Wegelin in an ovarian
      goiter].

PMID- 15445497
TI  - [Strangulation of the small intestine into the ligamentum latum. A contribution
      to the pathogenesis of strangulation ileus].

PMID- 15445498
TI  - [Gas exchange during the process of radiotherapy of patients with pulmonary
      cancer].

PMID- 15445499
TI  - Measurements of radioactivity in Warsaw, Poland, during the year 1959.

PMID- 15445500
TI  - [The value of the thymol flocculation test for the diagnosis of chronic
      hepatopathies].

PMID- 15445501
TI  - [Physiological-and foodstuff chemical problems on citric acid].

PMID- 15445502
TI  - [On non-arteriosclerotic circulatory disorders of the basilar artery].

PMID- 15445503
TI  - [Protective effect of S- and N,S-substituted beta-mercaptoethylamine on the
      animal organism under the influence of ionizing radiations].

PMID- 15445504
TI  - [The effect of lengthening or branching of the carbon chain on the protective
      action of beta-mercaptoethylamine during lesions caused by ionizing radiations].

PMID- 15445506
TI  - Chemical dosimetry of prompt and residual radiations from nuclear detonations.

PMID- 15445505
TI  - [The protective action of N-replaced beta-mercaptoethylamine in disorders due to
      ionizing radiations].

PMID- 15445507
TI  - [Fractionated properties of serum proteins during the acute action of ionizing
      radiation in conditions of stimulation and inhibition of the central nervous
      system].

PMID- 15445508
TI  - [Librium, a new pschotropic drug. First experiences in clinical and ambulatory
      practice].

PMID- 15445509
TI  - [Changes in the bone marrow in cancer patients during roentgenotherapy].

PMID- 15445510
TI  - [Cytochemistry of phosphatases, oxidases and peroxidases in hematopoietic
      elements in radiation injury].

PMID- 15445511
TI  - [Histidine, arginine and SH-compounds in blood and bone marrow cells and their
      changes under the influence of roentgen rays].

PMID- 15445512
TI  - [The general system of rehabilitation in motor infirmities].

PMID- 15445513
TI  - [The toothless mouth].

PMID- 15445514
TI  - [200 narcoses with hydroxydione in a regional hospital].

PMID- 15445515
TI  - [The contribution of rye to the nutritional needs of modern man].

PMID- 15445516
TI  - Distribution and excretion of niobium-95 in rats following daily administration
      in the food and drinking water.

PMID- 15445517
TI  - Distribution and excretion of thorium with emphasis upon route of injection and
      amount of carrier present.

PMID- 15445518
TI  - Mitochondrial swelling induced by thiophosphate, 2-mercaptoethylamine, and AET.

PMID- 15445519
TI  - [Changes in the reactivity of the large blood vessels in acute radiation
      sickness].

PMID- 15445520
TI  - [On the clinical picture of microlithiasis of the pulmonary alveoli].

PMID- 15445521
TI  - [On the diagnostic value of the skin sugar test].

PMID- 15445522
TI  - [Familial, non-spherocytic hemolytic anemia with excretion of porphyrin
      precursors (Crosby type)].

PMID- 15445523
TI  - [The effect of ionizing radiations on regularity of the vaccine process in BCG
      vaccination in experimental conditions].

PMID- 15445525
TI  - [Microbiological research and its fundamentals as created by Robert KOCH].

PMID- 15445524
TI  - [A new serological reaction for the diagnosis of infectious mononucleosis].

PMID- 15445526
TI  - [Experiences with sulfadimethyloxazole (Sulfuno) in urinary tract infections].

PMID- 15445527
TI  - [Contribution on the therapy of stomach- and duodenal ulcers].

PMID- 15445528
TI  - Uptake of radioisotopes and their transfer through food chains by marine
      organisms.

PMID- 15445529
TI  - [On prophylactic stimulation of thrombopoiesis by diphacil during the action of
      ionizing radiations].

PMID- 15445530
TI  - [Radiation injury of the fetus in utero. (Animal experiments].

PMID- 15445531
TI  - [Damage to the fetus maturing in utero by ionizing radiation].

PMID- 15445532
TI  - [Professional prohibition of pendulum diagnosis?].

PMID- 15445533
TI  - [Increase of the sensitivity in counters with horizontal lead housing for the
      measurement of preparations with low activity].

PMID- 15445534
TI  - [Medical professional secrecy with regard to traffic safety].

PMID- 15445535
TI  - [Results of research and progress in the field of legal medicine].

PMID- 15445536
TI  - [Suffocation in lithotomy position].

PMID- 15445537
TI  - [Clinical and experimental research on a new diuretic sulfonamide].

PMID- 15445538
TI  - [Secondary hyperaldosteronism with cyclic edema as a sequel to the chronic use of
      laxatives in a case of anorexia nervosa].

PMID- 15445539
TI  - [Congestion of vascular flow in the lower extremities in increased intra
      abdominal pressure].

PMID- 15445540
TI  - [On disorders of vulneary processes after total-body roentgen-irradiation].

PMID- 15445541
TI  - [On the course of experimental pulmonary candidiasis after roentgen-irradiation].

PMID- 15445542
TI  - Carisoprodol for muscular spasm and pain seen in industrial and general practice.

PMID- 15445543
TI  - Clinical evaluation of mebutamate, an antihypertensive agent: preliminary report.

PMID- 15445544
TI  - [On an unknown side-effect of treatment with glucocorticoids].

PMID- 15445546
TI  - [Against erroneous opinions on the surgical treatment of the gastroduodenal
      ulcer].

PMID- 15445545
TI  - [On functional activities of nodes and diffuse thyroid tissues in patients with
      endemic goiter].

PMID- 15445548
TI  - [The period before the heart infarct].

PMID- 15445547
TI  - [The effect of radiation on vitamin B-1 metabolism. Part 3. An analysis of the
      effect of radiation on the metabolism of vitamin B-1 with the aid of procaine
      block and the vitamin B-1 loading test].

PMID- 15445549
TI  - [The effective removal of clinical therapeutic difficulties in internal
      diseases].

PMID- 15445550
TI  - [On the concentration of radioactive iodine in tumors of the brain].

PMID- 15445551
TI  - [On introduction of the rad unit into the practice of medical radiology].

PMID- 15445552
TI  - [A comparison of the roentgen picture and lung function analysis in 1000 West
      German miners with silicosis].

PMID- 15445553
TI  - [Diphenoxylate treatment results in 264 cases of diarrhea].

PMID- 15445554
TI  - [Biosynthesis of the porphyrin system in the human leukocyte].

PMID- 15445555
TI  - [Studies on changes in the intestinal microflora in experimental radiation
      sickeness].

PMID- 15445556
TI  - [Research on the effects of Ripason in fatty liver].

PMID- 15445557
TI  - [Clinical-electrocardiographic changes in patients with thyrotoxicosis after
      therapy with radioactive iodine].

PMID- 15445558
TI  - [On the interrelations of autoinfection with leukopenia and connective tissue
      mast cell reactions in radiation injury].

PMID- 15445559
TI  - [On a patient with sideroblastic anemia and hemochromatosis].

PMID- 15445560
TI  - [To Professor Marc AMSLER on his 70th birthday].

PMID- 15445561
TI  - [The influence of human growth hormone on the metabolism and growth rate in
      pituitary dwarfism].

PMID- 15445562
TI  - [On the differential diagnosis of neonatal jaundice].

PMID- 15445563
TI  - [Pulmonary and pleural injuries].

PMID- 15445564
TI  - [On critical evaluation of the significance of "initial signs" of radiation
      cataract].

PMID- 15445565
TI  - [The use of blood substitutes in polonium injury (preliminary report)].

PMID- 15445566
TI  - [Clinical studies on monoamine metabolism under the influence of segontin].

PMID- 15445567
TI  - [Clinical and circulatory analytic testing of a Melilotus preparation].

PMID- 15445568
TI  - [On the preservation of insulin in a physiological sodium carbonate solution. On
      the problem of therapy of the diabetic coma with a continous intravenous drip
      infusion of insulin].

PMID- 15445569
TI  - Effect of neutron dose rate on the incidence of mammary tumors in female Sprague
      Dawley rats.

PMID- 15445570
TI  - Fertility of CF No. 1 female mice irradiated with fission neutrons.

PMID- 15445571
TI  - [The clinical significance of plasma lipids].

PMID- 15445572
TI  - [On the clinical aspects of rheumatism].

PMID- 15445573
TI  - [Distribution of depth doses from the telegamma apparatus with Cs137].

PMID- 15445574
TI  - [On the treatment of multiple myeloma with radioactive phosphorus].

PMID- 15445575
TI  - [Change in motor activity of rabbits after the action of radiations].

PMID- 15445576
TI  - [Comparative characteristics of leukocytic and temperature reactions as to the
      effect of radiations in animals].

PMID- 15445577
TI  - [The effect of seasonal factors on the injurious action of ionizing radiation].

PMID- 15445578
TI  - [On personnel training for radiotherapy departments and radiological
      laboratories].

PMID- 15445579
TI  - [Special methods in the surgery of anomalies of the pulmonary venous orifices
      with atrial septal defect].

PMID- 15445580
TI  - [Role of the caffeine load in the diagnosis of thyroid hyperfunction].

PMID- 15445581
TI  - [A rare form of meniscal lesion: the dog-ear tear].

PMID- 15445582
TI  - [Aging and geriatric diseases in psychiatry and neurology].

PMID- 15445583
TI  - [On the treatment of psychotic patients with fluphenazine].

PMID- 15445584
TI  - [On a preparation with reserpine-like effect].

PMID- 15445585
TI  - [On the history of the problem of biological regulation].

PMID- 15445586
TI  - [On the possibility of use of a tar xanyl ointment in various forms of eczema].

PMID- 15445587
TI  - [The role of physical and occupational therapy for rehabilitation within the
      framework of the law on disability insurance, and in particular, rehabilitation
      of rheumatic invalids].

PMID- 15445588
TI  - [Oral cholecysto-cholangiography].

PMID- 15445589
TI  - [Elimination of the hypophysis in surgery of breast cancer].

PMID- 15445590
TI  - Electron microscopic study of the fine structure of the fat cell as related to
      function.

PMID- 15445591
TI  - [Some immunochemical considerations on allergy to penicillin].

PMID- 15445592
TI  - [On the balneotherapy of hypertension].

PMID- 15445593
TI  - [Catecholamine excretion and blood circulation regulation in delirium tremens].

PMID- 15445594
TI  - [Frequent occurrence of Dupuytren's contracture in chronic alcoholism].

PMID- 15445595
TI  - [Amanita mushroom poisoning in childhood].

PMID- 15445596
TI  - [On the indication for alpha-phthalimidoglutarimide (contergan) in pediatrics].

PMID- 15445597
TI  - [On the clinical aspects of Waldenstroem's syndromes].

PMID- 15445598
TI  - [Male pseudohermaphroditism with testicular feminization].

PMID- 15445599
TI  - [Report on the therapy of liver diseases].

PMID- 15445600
TI  - [The gastrointestinal tract and the neurovegetative system].

PMID- 15445601
TI  - [On the etiology of multiple sclerosis].

PMID- 15445602
TI  - [Carcinoma of the penis. Zuerich experiences in the years 1926-1959].

PMID- 15445603
TI  - [Hypercalcemia syndrome and hypercalciuria].

PMID- 15445604
TI  - [Hypercalcemia syndrome and hypercalciuria].

PMID- 15445605
TI  - [Schiller's iodine test in the mouth].

PMID- 15445606
TI  - [Simple ulcer of the bladder. Interstitial ulcerous cystitis, Fenwick-Hunner
      ulcer].

PMID- 15445607
TI  - Hemopoietic preparation for pregnancy.

PMID- 15445608
TI  - [The incidence of malignant tumors of the digestive tract in autopsy material
      from the years 1901-1950 of the Pathologische Institut der Universitaet Zuerich].

PMID- 15445609
TI  - [The significance of electromyography in peripheral nerve injury].

PMID- 15445611
TI  - [Results of oral poliomyelitis vaccination in northeast Switzerland].

PMID- 15445610
TI  - [The significance of the reflux of the contrast medium into the hepatic duct in
      oral cholecytography].

PMID- 15445612
TI  - [On steroid therapy of severe chronic polyarthritis during physicobalneotherapy].

PMID- 15445613
TI  - [Generalized moniliasis of the skin in a newborn infant].

PMID- 15445614
TI  - [Observations on vaccinations during poliomyelitis outbreaks].

PMID- 15445615
TI  - [Results of treatment with spiramycin in bacterial infections of the respiratory
      tract].

PMID- 15445616
TI  - [The effect of peroral iron medication on hemoglobin formation at great heights,
      based on a study of the Swiss Dhaulagiri expedition of 1958].

PMID- 15445617
TI  - [On control of anticoagulant therapy].

PMID- 15445618
TI  - [On sleep disorders].

PMID- 15445619
TI  - [Staphylococcal pneumonia in children].

PMID- 15445620
TI  - [The orthopedic treatment of arthrosis deformans, especially that of arthrosis of
      the hip].

PMID- 15445621
TI  - [Advances in the treatment of so-called congenital hip dislocation].

PMID- 15445622
TI  - [On preparation for surgery in gynecology].

PMID- 15445623
TI  - [Studies on the problem of protein uptake in nucleated cells of peripheral blood
      and in histiocytes of exudate (pinocytosis)].

PMID- 15445624
TI  - [Thoracoscopic denervation in vegetative dystonia].

PMID- 15445625
TI  - [ACTH therapy in Morgagni-Adams-Stokes attacks].

PMID- 15445626
TI  - [Contribution to premedication in gynecological surgery].

PMID- 15445627
TI  - [Dysbacteria in relation to the endocrine system and metabolic indications for
      its therapy].

PMID- 15445628
TI  - [On the incidence of single diseases in general practice].

PMID- 15445629
TI  - [On the tolbutamide treatment of multiple sclerosis].

PMID- 15445630
TI  - [The leukocytes, serum proteins and the reticuloendothelial system].

PMID- 15445631
TI  - [Medicine in clinics, and free practice. A contribution to its discussion].

PMID- 15445632
TI  - [Goals and accomplishments of otosurgery today. IV. Audiological and surgical
      results of tympanoplasty, stapedolysis and fenestration].

PMID- 15445633
TI  - [Goals and accomplishments of present day otosurgery. I. On the physiology and
      pathology of hearing in the middle ear].

PMID- 15445634
TI  - [Goals and accomplishments of present-day otosurgery. II. Clinical indications
      and decisive factors for the surgical improvement of hearing].

PMID- 15445635
TI  - [Goals and accomplishments of present-day otosurgery. III. Methods and principles
      of surgery and tympanoplasty for otosclerosis].

PMID- 15445636
TI  - [Experiences with the new psychosedative "Librium" (Ro-50690) in an internal
      disease department].

PMID- 15445637
TI  - [Clinical research on the metabolic effects of a protein-anabolic hormone in
      childhood].

PMID- 15445638
TI  - [Effect of irradiation on myeloid cell lysis of the aqueous humor].

PMID- 15445639
TI  - [Clinical experiences with gerivit].

PMID- 15445640
TI  - [An apparatus for measuring tritium oxides].

PMID- 15445641
TI  - [Some problems in dosimetry of betatron radiation].

PMID- 15445642
TI  - [On postoperative radiotherapy of pulmonary carcinoma].

PMID- 15445643
TI  - [On teaching radiology in medical institutes].

PMID- 15445644
TI  - [2 additional cases of aortic rupture in blunt closed thoracic trauma].

PMID- 15445645
TI  - [Clinical verification of the Tokuoka spermine test].

PMID- 15445647
TI  - [On the etiology and pathogenesis of common hirsutism].

PMID- 15445646
TI  - [The significance of a correlative diagnosis in liver and spleen surgery].

PMID- 15445648
TI  - [Protective action of local asphyxia of the bone marrow in acute radiation injury
      in animals].

PMID- 15445649
TI  - [On the role of hypothermia produced with certain substances in the mechanism of
      radioprotective activity].

PMID- 15445650
TI  - [Radioprotective activity of certain tryptamine derivatives and their
      homologues].

PMID- 15445651
TI  - [Change in skin permeability under the influence of internal radiation with
      radioactive sodium].

PMID- 15445652
TI  - [On toxicity of irradiated and oxidized fats].

PMID- 15445653
TI  - [Vincent van Gogh and his physicians].

PMID- 15445654
TI  - [On the therapy of fractures with "bone glue"].

PMID- 15445655
TI  - [Some current problems of hypothermia].

PMID- 15445656
TI  - [Contribution to the pharmacology of Filatov's tissue therapy].

PMID- 15445657
TI  - [On the surgical treatment of hypertension caused by insufficient blood supply of
      the renal parenchyma].

PMID- 15445658
TI  - Clinical indications for gamma globulin therapy.

PMID- 15445659
TI  - [On the anthropology of the vegetative nervous system].

PMID- 15445660
TI  - Radiological survey of the health division diagnostic x-ray facility.

PMID- 15445661
TI  - Safe and effective treatment for otitis externa.

PMID- 15445662
TI  - [The continuous observation of changes in the blood circulation in the region of
      the internal carotid artery].

PMID- 15445663
TI  - Progress report: role of the small intestine in acute radiation death. I. Dose
      effect on the fourth postirradiation day.

PMID- 15445664
TI  - Hernias need not recur.

PMID- 15445665
TI  - [Whom should I marry?].

PMID- 15445666
TI  - Medical problems encountered in the handling of radiosotopes.

PMID- 15445667
TI  - Experimental radiation therapy of tumors using I 131 carrying antibodies to
      fibrin.

PMID- 15445668
TI  - Ethyl acetate extraction of uranium from human and animal tissues.

PMID- 15445670
TI  - Radiation protection standards.

PMID- 15445669
TI  - The Puerto Rico Nuclear Center--its aims, activities and plans.

PMID- 15445671
TI  - Toxicity and other hazards of beryllium and rocket propellants.

PMID- 15445672
TI  - Problems in the therapy of radiation sickness.

PMID- 15445673
TI  - The action of radiation on biologic materials.

PMID- 15445674
TI  - Medical uses of radioisotopes in Puerto Rico.

PMID- 15445675
TI  - Sr90 monitoring at the Savannah River Plant.

PMID- 15445676
TI  - Relation of adrenal cortical volume to survival following x-irradiation.

PMID- 15445677
TI  - Mechanism of clearance of inhaled particulates from the lung.

PMID- 15445678
TI  - The use of radioisotopes in metabolic studies.

PMID- 15445680
TI  - The radiological physics program at the University of Puerto Rico.

PMID- 15445679
TI  - A discussion of restraint and protection of the human experiencing the smooth and
      oscillating accelerations of proposed space vehicles.

PMID- 15445681
TI  - A stable continuously recording electrode system for the determination of oxygen
      dissolved in protein solutions.

PMID- 15445682
TI  - Technical consideration on survival measures and reduction of casualties.

PMID- 15445683
TI  - A theoretical andexperimental investigation of the temperature response of pig
      skin exposed to thermal radiation.

PMID- 15445684
TI  - Annual progress report. Radium and mesothorium poisoning and dosimetry and
      instrumentation techniques in applied radioactivity.

PMID- 15445685
TI  - An inhalation exposure to uranium tritaoctoxide.

PMID- 15445686
TI  - High G protection.

PMID- 15445687
TI  - Plutonium excretion following acute accidental exposure.

PMID- 15445688
TI  - Electrodeposition of enriched uranium in urine.

PMID- 15445689
TI  - Acceleration problems in space flight.

PMID- 15445690
TI  - The physiology of temperature regulation.

PMID- 15445691
TI  - A study of the possible relationship between radioactivity and toxicity in fishes
      from the Central Pacific.

PMID- 15445692
TI  - High specific activity iodination of gamma-globulin with iodine-131 monochloride.

PMID- 15445693
TI  - The University of Puerto Rico School of Medicine - past, present and future.

PMID- 15445694
TI  - Confinement techniques and handling of plutonium in research laboratories.

PMID- 15445695
TI  - Relationships between the geologic environment and mortality from congenital
      malformation.

PMID- 15445696
TI  - The determination of fluoride in human urine.

PMID- 15445697
TI  - G tolerance in primates. II. Observations on the relationship of carotid pressure
      and end point during acceleration.

PMID- 15445698
TI  - The use of low level scintillation spectroscopy in the evaluation of radioactive
      contamination of the human body.

PMID- 15445699
TI  - Chemical methods in the evaluation of human contamination.

PMID- 15445700
TI  - Immediate evaluation of doses from external radiation and from internal
      contaminations in the event of a radiation accident.

PMID- 15445701
TI  - Some physical and physiological factors controlling the fate of inhaled
      substances.

PMID- 15445702
TI  - Health physics aspects of basic medical research.

PMID- 15445704
TI  - Hormonal determinants of mammalian tolerance to acceleration stress.

PMID- 15445703
TI  - Preliminary studies on the mechanism of radiation damage to oxidative
      phosphorylation in spleen mitochondria.

PMID- 15445705
TI  - A cobalt and a tritium incident at Argonne National Laboratory.

PMID- 15445706
TI  - A physiological end point for the study of the tolerance of small mammals to high
      acceleration stress.

PMID- 15445707
TI  - [The literature program of the Literature cooperative for Medicine].

PMID- 15445709
TI  - Some effects of ultraviolet irradiation on yeast cells (Candida utilis).

PMID- 15445710
TI  - Immunochemical studies on mitochrome.

PMID- 15445712
TI  - The role of skin in heat transfer.

PMID- 15445711
TI  - Production of pain and thermal burns in skin areas previously exposed to
      ultraviolet radiation.

PMID- 15445713
TI  - X-irradiation and acceleration stress.

PMID- 15445714
TI  - Health physics training.

PMID- 15445715
TI  - Biological blast effects.

PMID- 15445717
TI  - [On fractures of the semilunar bone and their cure in comparison to necrosis of
      the semilunar bone].

PMID- 15445716
TI  - A review of significant Hanford plutonium deposition cases.

PMID- 15445718
TI  - The acute radiation syndrome. Urine analysis report.

PMID- 15445719
TI  - Hmatologic effects of the accidental radiation exposure at Y-12.

PMID- 15445720
TI  - The acute radiation syndrome. A medical report on the Y-12 accident. June 16,
      1958.

PMID- 15445721
TI  - The acute radiation syndrome.

PMID- 15445722
TI  - Study of the plasma coagulation factors in victims of the Y-12 accident at Oak
      Ridge.

PMID- 15445723
TI  - Personnel radiation monitoring from a criticality accident.

PMID- 15445724
TI  - Response of the burro exposed to an experimental nuclear excursion.

PMID- 15445725
TI  - The acute radiation syndrome. Serum protein studies.

PMID- 15445726
TI  - Spectral sensitivity of the eye based on visual acuity.

PMID- 15445727
TI  - Behavioral and physiological effects of exposure to a simulated Juno II
      acceleration pattern.

PMID- 15445728
TI  - [Histobacteriological research on lymphatic tuberculosis of guinea pigs treated
      with repeated cycles of isoniazid therapy].

PMID- 15445729
TI  - Clinical significance of serum glutamic oxalacetic transaminase test in medical
      diseases.

PMID- 15445730
TI  - Serum protein-bound hexose and serum protein-bound hexosamine in normal and
      silicotic subjects.

PMID- 15445731
TI  - Bactericidal power of human serum after massive irradiation.

PMID- 15445732
TI  - [Myocardial metabolism in coronary artery disease].

PMID- 15445733
TI  - Limitation of ocular motility and pupillary dilatation in humans due to positive
      acceleration.

PMID- 15445734
TI  - Weightlessness simulation by total body immersion: physiological effects.

PMID- 15445735
TI  - Some properties of reparable and irreparable radiation injury.

PMID- 15445736
TI  - Tritium handling.

PMID- 15445737
TI  - Pathologic effects of ingested strontium-90 in rats and monkeys.

PMID- 15445738
TI  - Concept and criteria of radiologic aging.

PMID- 15445739
TI  - Control performance under acceleration with side-arm attitude controllers.

PMID- 15445740
TI  - Preliminary report on an automated system for the study of mental function in the
      human subjected to acceleration stress.

PMID- 15445741
TI  - [The work capacity of chronic pneumopathic patients].

PMID- 15445742
TI  - Some medical contraindications to the use of the standard life jacket for
      survival.

PMID- 15445743
TI  - Fallout from USSR 1961 nuclear tests.

PMID- 15445744
TI  - Control of surgical infections.

PMID- 15445745
TI  - Non-penetrating chest injury resulting in isolated rupture of ventricular septum
      and angina pectoris.

PMID- 15445746
TI  - Use of appetite-suppressant drugs for weight reduction without dieting.

PMID- 15445747
TI  - Clinical study of a non-narcotic combination for relief of postpartum pain.

PMID- 15445748
TI  - Musculoskeletal disorders amenable to treatment with intravenous methocarbamol.

PMID- 15445749
TI  - Prophylactic use of antimicrobial agents with particular reference to toxic
      reactions and development of resistant strains.

PMID- 15445750
TI  - Pseudomonas-contaminated fluorescein stock solution.

PMID- 15445751
TI  - Doctors and the law.

PMID- 15445752
TI  - Doctors and the law.

PMID- 15445753
TI  - Doctors and the law.

PMID- 15445754
TI  - Doctors and the law.

PMID- 15445755
TI  - Doctors and the law.

PMID- 15445756
TI  - Doctors and the law.

PMID- 15445757
TI  - Doctors and the law.

PMID- 15445758
TI  - Doctors and the law.

PMID- 15445759
TI  - Evaluation of factors in the elution of hydrocortisone from paper chromatograms.

PMID- 15445760
TI  - Medical problems encountered in rehabilitation.

PMID- 15445761
TI  - Relief of eclamptic convulsions with chlordiazepoxide.

PMID- 15445762
TI  - The influence of adrenalectomy on the metabolic actions of glucagon in the fasted
      rat.

PMID- 15445763
TI  - Leucorrheal vulvar pruritus: preliminary report of treatment technique.

PMID- 15445765
TI  - The liver in diabetes mellitus.

PMID- 15445764
TI  - A clinical study of four anticholinergic drugs combined with tranquilizers or
      sedatives.

PMID- 15445766
TI  - [Some therapeutic complications recently reported in neuropsychiatry].

PMID- 15445767
TI  - Methods research.

PMID- 15445768
TI  - The presence or absence of visual coriolis illusions at various combined angular
      velocities.

PMID- 15445769
TI  - Dimethpyrindene in pruritic and allergic skin disorders.

PMID- 15445770
TI  - [Arteriosclerosis and electrotherapy].

PMID- 15445771
TI  - Head and neck cancer: general considerations.

PMID- 15445772
TI  - Prolotherapy for sciatica from weak pelvic ligaments and bone dystrophy.

PMID- 15445774
TI  - [On the change in polarization resistance and polarization capacity of the human
      body by vegetative drugs].

PMID- 15445773
TI  - Clinical experience with promethazine and meperidine in relief of pain.

PMID- 15445776
TI  - Management of pruritus.

PMID- 15445775
TI  - Carotid-cavernous fistula: ocular findings in 17 cases.

PMID- 15445778
TI  - Review of clinical use of hydroxyphenamate in 1759 patients.

PMID- 15445780
TI  - [Interesting "function" tests at the Medizinische Universitaetsklinik Bonn
      Venusberg].

PMID- 15445779
TI  - [Biological effects of microwaves].

PMID- 15445777
TI  - Sedative-antispasmodic in relief of gastrointestinal symptoms.

PMID- 15445781
TI  - [The most recent advances in medical electronics].

PMID- 15445782
TI  - [Work efficiency and the 5-day week. (A friendly contribution to increase in work
      efficiency and improvement of the health of the reader)].

PMID- 15445783
TI  - Safe relief of pain during labor with dimenhydrinate.

PMID- 15445784
TI  - New dosage therapy with oral chymotrypsin.

PMID- 15445785
TI  - A few points about the eyes--some of them unorthodox.

PMID- 15445786
TI  - Hemolytic disease of the newborn due to Rh-immunization: treatment.

PMID- 15445787
TI  - Clinical evaluation of vaginal jelly alone in the management of fertility.

PMID- 15445788
TI  - Simple, reliable tests for some common poisons and drug overdosage.

PMID- 15445789
TI  - Relief of bronchospasm with oral theophylline.

PMID- 15445790
TI  - Management of psychiatric disorders with Diazepam.

PMID- 15445791
TI  - Therapeutic and prophylactic use of triclobisonium chloride in gynecology and
      obstetrics.

PMID- 15445792
TI  - The effect of deposition rate and cumulative soil level on the concentration of
      strontium-90 in U.S. milk and food supplies.

PMID- 15445793
TI  - The ill effects of sunlight.

PMID- 15445794
TI  - [The electrical accident. Anatomical, physiological, clinical, neurological,
      psychological studies and technical analyses after accidents caused by
      alternating and direct voltage. (Critical study of 1250 cases)].

PMID- 15445795
TI  - Artificial ionization of the air and its biological significance.

PMID- 15445796
TI  - [Vegetative constitution and electrical accident].

PMID- 15445797
TI  - Evaluation of an antipyretic-analgesic combination in a pediatric practice.

PMID- 15445798
TI  - [Some new therapeutic acquisitions in neuropsychiatry].

PMID- 15445799
TI  - [Physical medicine and rehabilitation in America].

PMID- 15445800
TI  - Evaluation of chlormezanone as a clinical and postoperative central relaxant and
      tranquilizer.

PMID- 15445801
TI  - A suction pump for pleural space aspiration.

PMID- 15445802
TI  - Closed thoracotomy with trocar and catheter sealed in plastic bag.

PMID- 15445803
TI  - Prevention of otitis in individuals using contaminated swimming pools:
      preliminary report.

PMID- 15445804
TI  - [Some new therapeutic data concerning the diseases of the digestive apparatus].

PMID- 15445805
TI  - Place of radiotherapy in treatment of cancer of larynx.

PMID- 15445806
TI  - Digestive enzymes for infant colic: preliminary report.

PMID- 15445807
TI  - Relief of back and sciatic pain by prostato-vesicular massage-stripping.

PMID- 15445808
TI  - [Treatment of essential insomnia].

PMID- 15445809
TI  - Evaluation of four hydrolytic enzymes in chronic cases of functional digestive
      disorders.

PMID- 15445810
TI  - Effect of dextro-thyroxine on serum cholesterol levels.

PMID- 15445811
TI  - Use of muscle-relaxing tranquilizer in ambulatory patients.

PMID- 15445813
TI  - Dupuytren's contracture.

PMID- 15445812
TI  - Oxalosis: case report in Negro girl.

PMID- 15445814
TI  - Benzonatate as cough and gag reflex suppressive.

PMID- 15445815
TI  - Nasopharyngeal balloon catheter.

PMID- 15445816
TI  - Pulsed high frequency and routine hospital antibiotic therapy in the management
      of pelvic inflammatory disease: a preliminary report.

PMID- 15445817
TI  - Evaluation of topical and internal medications containing essential unsaturated
      fatty acids in treatment of common dermatoses.

PMID- 15445818
TI  - Treatment of resistant verruca vulgaris with bismuth sodium triglycollamate.

PMID- 15445819
TI  - The treatment of burns.

PMID- 15445820
TI  - The muscular dystrophies.

PMID- 15445821
TI  - Surgical injuries of the bladder and ureter.

PMID- 15445822
TI  - Tolerance to repeated application of a foam contraceptive in the human vagina.

PMID- 15445823
TI  - Osteoporosis.

PMID- 15445824
TI  - Management of bacterial infections of the skin.

PMID- 15445825
TI  - Use of a lipoprotein-nucleic acid compound in treatment of infectious
      mononucleosis.

PMID- 15445826
TI  - Clinical evaluation of an antihistaminic compound, dimethpyrindene maleate.

PMID- 15445827
TI  - A survey of modern methods of proctologic examinations.

PMID- 15445828
TI  - [Possibilities of blockade of the stellate ganglion with stimulating current].

PMID- 15445829
TI  - Role of the physician in diagnosis and management of glaucoma.

PMID- 15445830
TI  - Management of leg cramps in pregnancy with isoxsuprine hydrochloride.

PMID- 15445831
TI  - Management of steriod-responsive dermatologic disorders with betamethasone.

PMID- 15445832
TI  - Results of therapy with topical antiinfective agent.

PMID- 15445833
TI  - Diagnosis and treatment of carcinoma of the lung.

PMID- 15445834
TI  - Sulfadimethoxine in the treatment of pustular acne vulgaris.

PMID- 15445835
TI  - Immunization against tetanus saves many from tragic death.

PMID- 15445836
TI  - Orally-administered poliomyelitis vaccine proves effective.

PMID- 15445837
TI  - Symptoms, signs and findings in cases of brain tumor.

PMID- 15445838
TI  - The management of gastric ulcer.

PMID- 15445839
TI  - Vaccination urged against influenza.

PMID- 15445840
TI  - Corticosteroids in management of stasis ulcers.

PMID- 15445841
TI  - Management of gastrointestinal disorders with glycopyrrolate in general practice.

PMID- 15445842
TI  - Injectable methylprednisolone.

PMID- 15445843
TI  - Antrectomy with vagectomy for chronic duodenal ulcer.

PMID- 15445844
TI  - Management of insomnia in gynecologic and obstetric patients.

PMID- 15445845
TI  - Hexamethonium in the treatment of acute pulmonary edema.

PMID- 15445846
TI  - Radiobiological review articles. A literature search.

PMID- 15445847
TI  - Pruritus, skin disorders, and trimeprazine.

PMID- 15445848
TI  - Clinical evaluation of an expectorant in an industrial facility.

PMID- 15445849
TI  - Increase in acceleration tolerance of the rat by 2-dimethylaminoethyl p
      chlorophenoxyacetate (Lucidril).

PMID- 15445850
TI  - Duodenal obstruction due to gallstone.

PMID- 15445851
TI  - The doctor and his federal income tax.

PMID- 15445852
TI  - Observations on the effects of a narcotic, including accidental overdosage.

PMID- 15445853
TI  - An antibacterial local anesthetic agent in the treatment of oropharyngeal
      conditions.

PMID- 15445854
TI  - Hydrochlorothiazide with potassium in resistant exogenous obesities.

PMID- 15445855
TI  - Current concepts of prophylactic and active treatment of shock.

PMID- 15445856
TI  - Incidence and treatment of ectopia vesicae.

PMID- 15445857
TI  - Vasodynamic relations in shock.

PMID- 15445858
TI  - Tuberculin testing using gun modification of head multiple-puncture technique.

PMID- 15445859
TI  - Clinical study of deserpidine-methamphetamine-pentobarbital combination in
      hypertension.

PMID- 15445860
TI  - Pediatric use of ferrocholinate.

PMID- 15445861
TI  - Co-existence of lung cancer and pulmonary tuberculosis.

PMID- 15445863
TI  - Nitrites in the treatment of angina pectoris.

PMID- 15445862
TI  - The allergic concept of infectious disease.

PMID- 15445864
TI  - An effective symptomatic treatment of migraine.

PMID- 15445865
TI  - Clinical study of little stroke in 112 cases.

PMID- 15445866
TI  - Herpes zoster opthalmicus: systemic steroid therapy.

PMID- 15445867
TI  - Electrocautery for ulcers of aphthous stomatitis.

PMID- 15445868
TI  - Death-producing dermatoses.

PMID- 15445869
TI  - [On the advantages of television in the therapy plan for ultrahard radiation].

PMID- 15445870
TI  - Recent developments in psychosomatic medicine.

PMID- 15445871
TI  - Burns and their care.

PMID- 15445873
TI  - Recognition and treatment of depression with amitriptyline.

PMID- 15445872
TI  - Management of impacted cerumen in pediatric patients.

PMID- 15445874
TI  - Estrogentranquilizer therapy for the menopausal patient.

PMID- 15445876
TI  - Principles of treatment of the injured hand.

PMID- 15445875
TI  - Delayed appearance of metastasis from hypernephroma of the kidney.

PMID- 15445877
TI  - Concept and treatment of the intestinal distress syndrome.

PMID- 15445878
TI  - Man in numbers.

PMID- 15445879
TI  - Long-term ovulation control with oral synthetic progestin.

PMID- 15445880
TI  - Treatment of obesity with long-acting form of carboxyphen-butabarbital.

PMID- 15445881
TI  - Combined use of aerosol and tablets for control of asthmatic symptoms.

PMID- 15445882
TI  - Response of microwave treated dogs to ionizing radiation.

PMID- 15445883
TI  - Uptake of radioisotopes and their transfer through food chains by marine
      organisms.

PMID- 15445884
TI  - Appetite control in pregnancy using combined prochlorperazine-dextroamphetamine.

PMID- 15445885
TI  - Meteorological evaluation of radioactive fallout.

PMID- 15445886
TI  - Observations on the relationships between human acceleration end points and the
      centrifuge acceleration pattern.

PMID- 15445887
TI  - Recording instrument for environmental testing of biological specimens.

PMID- 15445888
TI  - Evaluation of orphenadrine citrate in the treatment of orthopedic problems.

PMID- 15445889
TI  - Observations on the use of carbazochrome salicylate in surgical practice.

PMID- 15445890
TI  - Chlordiazepoxide as a preoperative and postoperative medication.

PMID- 15445891
TI  - Use of promethazine in medication of surgical patients.

PMID- 15445892
TI  - Pharmacological and toxicological studies on cephalotin.

PMID- 15445893
TI  - Repairs to the plumbing.

PMID- 15445894
TI  - The enigmatic thymus.

PMID- 15445895
TI  - Surface tension.

PMID- 15445896
TI  - High pressure oxygen: a high pressure treatment.

PMID- 15445897
TI  - Vulnerable viruses.

PMID- 15445898
TI  - Treatment of seborrhea capitis with biphenamine hydrochloride.

PMID- 15445899
TI  - Use of chlordiazepoxide in obese patients.

PMID- 15445900
TI  - A young hypertensive.

PMID- 15445901
TI  - Cancer of the cervix: Detection, treatment and prognosis.

PMID- 15445902
TI  - Triamcinolone acetonide ointment in psoriasis and other dermatoses: a new method
      of topical application.

PMID- 15445903
TI  - Comparative topical effectiveness of flurandenolone.

PMID- 15445904
TI  - Clinical evaluation of an antimicrobial cleansing ointment.

PMID- 15445905
TI  - Synthetic penicillin in treatment of Staphylococcus aureus infections of the skin
      in psychiatric patients.

PMID- 15445906
TI  - Effect of sodium dextrothyroxine in patients receiving anticoagulants.

PMID- 15445907
TI  - A summary of incidents involving USAEC shipments of radioactive material 1957
      1961.

PMID- 15445908
TI  - Variant angina pectoris of Prinzmetal.

PMID- 15445909
TI  - Increased concentration of topical corticosteroid more effective than increased
      frequency of application in dermatoses.

PMID- 15445910
TI  - Surgical correction of obstructing peptic ulcers in two children.

PMID- 15445911
TI  - Peptic ulcer: treatment with a combination of meprobamate and tridihexethyl
      chloride.

PMID- 15445912
TI  - Present status of cesarean section.

PMID- 15445913
TI  - Mushroom poisoning: three cases with one death.

PMID- 15445914
TI  - Tetanus toxoid prophylaxis: a great need for the young, for adults, and for the
      old.

PMID- 15445915
TI  - Preoperative use of a timed-release hypnotic: double blind study.

PMID- 15445916
TI  - Undiagnosed spontaneous rupture of umbilical cord.

PMID- 15445917
TI  - Surgical treatment of peptic esophagitis.

PMID- 15445918
TI  - Ferrous fumarate: a well tolerated oral iron preparation.

PMID- 15445919
TI  - Anorectal pain: its causes and management.

PMID- 15445920
TI  - Clinical determination of the dose response curve of methdilazine hydrochloride
      in allergic disorders.

PMID- 15445921
TI  - Treatment of allergic disorders with a combination agent.

PMID- 15445922
TI  - Repository steroid treatment of allergic skin and respiratory conditions.

PMID- 15445923
TI  - The changing clinical pattern of cardiac arrest.

PMID- 15445924
TI  - Lever displacement during continuous reinforcement and during a "discrimination".

PMID- 15445925
TI  - Treatment of acute and chronic alcoholism with promazine.

PMID- 15445926
TI  - Diagnosis and management of pancreatitis.

PMID- 15445927
TI  - Choline salicylate as an antipyretic and analgesic in pediatric practice.

PMID- 15445928
TI  - Bacterial susceptibility patterns as related to geographic variation and
      anatomical source.

PMID- 15445929
TI  - Doctors and the law.

PMID- 15445930
TI  - Evaluation and pattern response of a benzquinamide in 50 patients.

PMID- 15445931
TI  - Modern treatment of intestinal parasites.

PMID- 15445932
TI  - Clinical effects of metha drostenolone in urology.

PMID- 15445934
TI  - Doctors and the law.

PMID- 15445933
TI  - A low pH powder for the prevention of urethritis, skenitis, cystitis, vaginitis
      and cervical ulcers and for destroying cervical ulcers.

PMID- 15445935
TI  - Doctors and the law.

PMID- 15445936
TI  - Doctors and the law.

PMID- 15445937
TI  - Doctors and the law.

PMID- 15445938
TI  - Doctors and the law.

PMID- 15445939
TI  - Clinical trial of buccal or sublingual amylase in inflammations.

PMID- 15445940
TI  - Antibody response and survival after booster injections of poliomyelitis vaccine.

PMID- 15445941
TI  - Aerospace medical aspects of U. S. Navy manned balloon flight of 4 May 1961
      "Strato-Lab High No. 5".

PMID- 15445942
TI  - Reduction of elevated chylomicron levels with sublingual heparin potassum.

PMID- 15445943
TI  - Problems associated with evaluation of new oral and topical compounds for
      possible antifungal activity.

PMID- 15445944
TI  - Therapy of urinary tract infections based on in vitro studies with a combination
      of sulfamethylthiadiazole and methenamine mandelate.

PMID- 15445945
TI  - Clinical applications of a food concentrate as adjuvant therapy in disease.

PMID- 15445946
TI  - Symetine hydrochloride in the treatment of amebic liver abscess in guinea pigs.

PMID- 15445947
TI  - Use of analgesic combination in general practice.

PMID- 15445949
TI  - Treatment of gangrene of the extremities.

PMID- 15445948
TI  - Symptomatic relief of acute rhinitis with combination agent.

PMID- 15445950
TI  - Benign recurrent intrahepatic cholestasis.

PMID- 15445951
TI  - Observations on the use of a modified Grafenberg ring for contraception: a
      prelininary report.

PMID- 15445952
TI  - Enterobiasis: diagnosis and therapy.

PMID- 15445953
TI  - Flame contact studies. II. Experimental validation of mathematical analysis of
      heat flow.

PMID- 15445954
TI  - Elimination of Sh. sonnei from the stools by colistin sulphate.

PMID- 15445955
TI  - Radiation therapy of benign conditions.

PMID- 15445956
TI  - Clinical trial with methyprylon in patients with chronic insomnia.

PMID- 15445958
TI  - [Clinical and electrocardiographic observations on 6 men following lightning
      strokes].

PMID- 15445957
TI  - Oxethazaine hydrochloride for treatment of gastritis, peptic ulcer and
      esophagitis.

PMID- 15445959
TI  - Self-destructiveness and self-preservation.

PMID- 15445960
TI  - [An electronic console for monitoring heart operations].

PMID- 15445961
TI  - The effect of hypothermia on the rat's tolerance to high positive acceleration
      with evidence for the existence of different acceleration syndromes at high and
      low G.

PMID- 15445962
TI  - Flame contact studies. III. Determination of thermal properties of materials in
      thin layers.

PMID- 15445963
TI  - Flame contact studes. I. Apparatus and method for determination of heat transfer
      through fabric during flame contact.

PMID- 15445964
TI  - Thermistor system for measuring thermal gradients.

PMID- 15445965
TI  - Manifestation of integration in the regenerative process.

PMID- 15445966
TI  - Bilateral tubal pregnancy.

PMID- 15445967
TI  - Etiology, diagnosis, and therapy of prutitus ani.

PMID- 15445968
TI  - Preliminary investigation of viable Lactobacillus acidophilus instillation in
      vaginal pruritus.

PMID- 15445969
TI  - Development of phentermine, an appetite-control drug.

PMID- 15445970
TI  - Combined d-amphetamine and chlordiazepoxide therapy in the emotionally disturbed
      obese patient.

PMID- 15445971
TI  - A clinical evaluation of benzquinamide with observations on the total activity
      potential.

PMID- 15445972
TI  - Use of carisoprodol for musculoskeletal traumas.

PMID- 15445973
TI  - A hydroquinone effect.

PMID- 15445974
TI  - Oral hypoglycemic agent in the therapy of anogenital eczema.

PMID- 15445975
TI  - Investigation of phenyramidol for relief of musculoskeletal pain in an industrial
      population.

PMID- 15445977
TI  - Otitis externa: clinical aspects and bacteriologic studies.

PMID- 15445976
TI  - Oral antibiotics and serum cholesterol level in man.

PMID- 15445978
TI  - Data reduction by digital computer.

PMID- 15445979
TI  - Fetal distress.

PMID- 15445980
TI  - Clinical management of chronic recurrent urticaria.

PMID- 15445981
TI  - Apparent synergy between penicillin and erythromycin or fusidic acid.

PMID- 15445983
TI  - The perception of oculogravic illusions by inverted subjects.

PMID- 15445982
TI  - Encapsulation of humans in rigid polyurethane foam for use as a restraint system
      in high acceleration environments.

PMID- 15445984
TI  - Treatment of acne vulgaris.

PMID- 15445985
TI  - Evaluation of oral and parenteral proteolytic enzymes as anti-inflammatory
      agents.

PMID- 15445986
TI  - Hypothermia in treatment of esophageal hemorrhage.

PMID- 15445987
TI  - Clinical experience with anticholinergic-tranquilizer in gastrointestinal
      disorders.

PMID- 15445988
TI  - Prevention and management of respiratory complications in surgery.

PMID- 15445989
TI  - Iron-carbohydrate complex in treatment of iron-deficiency anemia of children.

PMID- 15445990
TI  - Evaluation of topical vitamin preparation in selected dermatoses.

PMID- 15445991
TI  - [Development of hearing aids].

PMID- 15445992
TI  - Three malignant tumors in one patient.

PMID- 15445993
TI  - X-ray of the abdominal aorta in detection of atherosclerosis.

PMID- 15445994
TI  - Environmental beta-gamma radioactivity in air at Sandia Laboratory, second
      quarter 1961.

PMID- 15445995
TI  - Environmental beta-gamma radioactivity in air at Sandia laboratory third quarter
      1961.

PMID- 15445996
TI  - Use of soap-free cleanser: preliminary report.

PMID- 15445997
TI  - [Electronic equipment in heart surgery].

PMID- 15445998
TI  - Prostatectomy: an explanation for the patient.

PMID- 15445999
TI  - Cholecystography.

PMID- 15446000
TI  - Nonpenetrating injuries of the chest.

PMID- 15446001
TI  - Extensive sphincterotomy with hemorrhoidectomy and other anal surgery.

PMID- 15446003
TI  - Temporal arteritis resulting in infected gangrene of tongue.

PMID- 15446002
TI  - Use of anti-inflammatory enzymes in 889 episiotomy patients.

PMID- 15446004
TI  - Leukoplakia and associated carcinoma of the oral mucosa.

PMID- 15446005
TI  - Control of weight gain in pregnancy: double blind study of a dieting aid.

PMID- 15446007
TI  - Non-penetrating abdominal trauma.

PMID- 15446006
TI  - The doctor builds his estate.

PMID- 15446008
TI  - Topical steroid therapy with flurandrenolone.

PMID- 15446009
TI  - Chronic ventilatory insufficiency and its management.

PMID- 15446010
TI  - Evaluation of tuboplasty following 12 years' experience.

PMID- 15446011
TI  - Effects of acceleration on pilot performance.

PMID- 15446012
TI  - Effects of positive pressure breathing on performance during acceleration.

PMID- 15446013
TI  - Problems and research in space psychology.

PMID- 15446014
TI  - [Method for testing analgesia in animal experiments].

PMID- 15446015
TI  - Treatment of cystic acne and other dermatoses with betamethasone.

PMID- 15446016
TI  - Nebulization of a superheated mixture as a vehicle for bronchodilator therapy.

PMID- 15446017
TI  - Suppurative periodontitis (pyorrhea): a medical and dental problem.

PMID- 15446018
TI  - Reversible free radical generation in the melanin granules of the eye by visible
      light.

PMID- 15446019
TI  - A study of trimethobenzamide, an antiemetic, in surgical patients.

PMID- 15446020
TI  - Complications of peptic ulcer following acute myocardial infarction.

PMID- 15446021
TI  - Neuromuscular changes associated with diverticula of the esophagus.

PMID- 15446022
TI  - Extended- and point-source radiometric program.

PMID- 15446023
TI  - Conservative management of rheumatoid arthritis.

PMID- 15446024
TI  - Sulfhemoglobinemia: report of an unusual case.

PMID- 15446028
TI  - Age and automotive accidents.

PMID- 15446029
TI  - Treatment of fungus infections of the skin with antibiotics.

PMID- 15446030
TI  - Reports on atomic radiation submitted to the United Nations Scientific Committee
      on the Effects of Atomic Radiation. (Supplement 1).

PMID- 15446031
TI  - Gamma ray exposure dose to non-urban populations from the surface deposition of
      nuclear test fallout.

PMID- 15446032
TI  - [The electric accident. Anatomical, physiological, clinical, neurological,
      psychological studies and technical analyses following accidents with AC and DC
      current. (Critical observation of 1250 cases)].

PMID- 15446033
TI  - Role of the day hospital in rehabilitation of mental patients.

PMID- 15446034
TI  - Good managers lead but also teach leadership.

PMID- 15446035
TI  - Perennial allergic rhinitis.

PMID- 15446037
TI  - GROWING OLD.

PMID- 15446038
TI  - DOCTORS AND THE LAW.

PMID- 15446039
TI  - PRACTICAL PROBLEMS IN INTERPRETATION OF PROTEIN BOUND IODINE TEST.

PMID- 15446040
TI  - TREATMENT OF GASTROINTESTINAL DISORDERS WITH A COMBINATION OF TRIFLUOPERAZINE AND
      ISOPROPAMIDE.

PMID- 15446041
TI  - THE EVALUATION OF NIALAMIDE IN POSTOPERATIVE DEPRESSIVE STATES.

PMID- 15446042
TI  - TOPICAL AGENTS USED IN TREATMENT OF ACNE.

PMID- 15446043
TI  - ACTINOSPECTACIN.

PMID- 15446044
TI  - DERMATITIS HERPETIFORMIS: A CHRONIC DERMATOSIS YIELDS TO SULFONES.

PMID- 15446045
TI  - LABORATORY EVALUATION OF AN IMMUNOLOGIC PREGNANCY TEST.

PMID- 15446046
TI  - TIMED-DISINTEGRATION TABLETS OF GLYCERYL TRINITRATENIACIN IN ANGINA PECTORIS.

PMID- 15446047
TI  - THE ADJUNCTIVE ROLE OF DIAZEPAM IN THE TREATMENT OF DEPRESSION.

PMID- 15446048
TI  - THE DOCTOR AND HIS FEDERAL INCOME TAX.

PMID- 15446049
TI  - THE DOCTOR AND DISASTER MEDICINE.

PMID- 15446050
TI  - REDUCING HAZARDS FOR HOSPITAL PATIENTS.

PMID- 15446051
TI  - PHYSIOLOGIC CONSIDERATIONS IN THE DIAGNOSIS OF RENAL HYPERTENSION.

PMID- 15446052
TI  - ANGINA PECTORIS--AN EFFECTIVE THERAPEUTIC APPROACH.

PMID- 15446053
TI  - PRURITUS OF DERMATOSES TREATED ADJUNCTIVELY WITH ORAL CLEMIZOLE HYDROCHLORIDE.

PMID- 15446054
TI  - EFFICACY OF TRIAMCINOLONE ACETONIDE OINTMENT 0.025 PER CENT IN 54 SELECTED
      PATIENTS.

PMID- 15446055
TI  - SCUBA DIVING AND DECONGESTANTS.

PMID- 15446056
TI  - CLINICAL TRIAL OF AN ANTIHISTAMINE FOR RELIEF OF PRURITUS.

PMID- 15446057
TI  - PHENOXYPROPYL PENICILLIN (PA-248) IN STREPTOCOCCAL AND STAPHYLOCOCCAL INFECTIONS.

PMID- 15446058
TI  - BENZODIAZEPINES IN THE DIFFERENTIATION AND TREATMENT OF  ANXIETIES.

PMID- 15446060
TI  - THE DOCTOR BUILDS HIS ESTATE.

PMID- 15446059
TI  - DOCTORS AND THE LAW.

PMID- 15446061
TI  - THE DOCTOR AND HIS FEDERAL INCOME TAX.

PMID- 15446062
TI  - THE DOCTOR AND DISASTER MEDICINE.

PMID- 15446063
TI  - ACUTE DISABILITIES IN THE U.S.A. NATIONAL CENTER FOR HEALTH STATISTICS.

PMID- 15446064
TI  - PITFALLS IN THE DIAGNOSIS AND TREATMENT OF CARDIAC FAILURE.

PMID- 15446065
TI  - PSYCHOTHERAPEUTIC DRUGS IN THE TREATMENT OF DEPRESSIONS.

PMID- 15446066
TI  - A PROPOSED HYPERTENSION SEVERITY INDEX.

PMID- 15446067
TI  - TREATMENT OF FUNGUS INFECTIONS WITH MICROCRYSTALLINE GRISEOFULVIN.

PMID- 15446068
TI  - ERADICATION OF STREPTOCOCCI BY ORAL ALPHA-PHENOXYPROPYL PENICILLIN.

PMID- 15446069
TI  - BEHAVIOR REACTION-TIME EFFECTS OF BENZQUINAMIDE IN INSTITUTIONALIZED PSYCHOTICS.

PMID- 15446070
TI  - CLINICAL SYNDROMES COMPLICATED BY PROTEIN DEPLETION TREATED WITH OXYMETHOLONE.

PMID- 15446071
TI  - UNUSUAL LESION OF THE COLON.

PMID- 15446072
TI  - DOCTORS AND THE LAW.

PMID- 15446073
TI  - THE DOCTOR AND HIS FEDERAL INCOME TAX.

PMID- 15446074
TI  - THE DOCTOR BUILDS HIS ESTATE.

PMID- 15446075
TI  - THE DOCTOR AND DISASTER MEDICINE.

PMID- 15446076
TI  - CLINICAL TRIAL OF CHLORPHENESIN CARBAMATE IN PATIENTS WITH MUSCLE SPASM.

PMID- 15446077
TI  - LOW-DOSAGE BENDROFLUMETHIAZIDE IN THE MANAGEMENT OF EDEMA AND HYPERTENSION.

PMID- 15446078
TI  - CLINICAL EVALUATION OF COMBINED ORPHENADRINE-FLUPHENAZINE IN ACUTE AND CHRONIC
      MUSCULOSKELETAL DISORDERS.

PMID- 15446079
TI  - BIZARRE REACTIONS.

PMID- 15446080
TI  - A NEW APPROACH TO THE HOSPITALIZATION OF THE MENTALLY ILL.

PMID- 15446081
TI  - ADJUVANT TREATMENT OF OBESITY WITH AN ANORECTIC-CALORIGENIC AGENT.

PMID- 15446082
TI  - PARENTERAL METHYLPREDNISOLONE ACETATE IN THE MANAGEMENT OF ARTHROPATHIES.

PMID- 15446083
TI  - ORAL AND TOPICAL TREATMENT OF TINEA PEDIS.

PMID- 15446084
TI  - MORNING STIFFNESS IN ARTHRITIS.

PMID- 15446085
TI  - CURRENT STATUS OF SYMPATHECTOMY.

PMID- 15446086
TI  - SYNTHESIS OF CEPHALOSPORIN C BY RESTING CELLS OF CEPHALOSPORIUM SP.

PMID- 15446087
TI  - EVALUATION OF TRIMETHOBENZAMIDE WITH PYRIDOXINE IN NAUSEA AND VOMITING OF
      PREGNANCY.

PMID- 15446088
TI  - TRAUMATIC INJURIES.

PMID- 15446089
TI  - INCIDENCE AND SUSCEPTIBILITY TO ANTIBIOTICS OF BACTERIA    CAUSING COMMON
      INFECTIONS IN A GENERAL HOSPITAL.

PMID- 15446090
TI  - A CASE OF SPONTANEOUS HEMOTHORAX WITH UNUSUAL FEATURES.

PMID- 15446091
TI  - DOCTORS AND THE LAW.

PMID- 15446092
TI  - DOCTOR AND HIS FEDERAL INCOME TAX.

PMID- 15446093
TI  - THE DOCTOR BUILDS HIS ESTATE.

PMID- 15446094
TI  - THE DOCTOR AND DISASTER MEDICINE.

PMID- 15446095
TI  - THE AGE FACTOR IN THE SHEFFIELD CUTLERY INDUSTRY.

PMID- 15446096
TI  - PARENTAL ROLES AS SEEN BY YOUNG CHILDREN IN DOLL PLAY.

PMID- 15446097
TI  - CHANGES IN ASSOCIATIVE BEHAVIOR DURING LATER YEARS OF LIFE:  A CROSS-SECTIONAL
      ANALYSIS.

PMID- 15446098
TI  - [ON THE FATHER PROBLEM IN THE DEVELOPMENT OF THE MALE CHILD].

PMID- 15446099
TI  - RESPONSE ALTERNATION IN CHILDREN: A DEVELOPMENTAL STUDY OF ORIENTATIONS TO
      UNCERTAINTY.

PMID- 15446100
TI  - THE PHYSICIAN'S FEDERAL INCOME TAX GUIDE.

PMID- 15446101
TI  - RAINFALL AND MONSTERS.

PMID- 15446102
TI  - DOCTORS AND THE LAW.

PMID- 15446103
TI  - ALLERGY IS A METABOLIC DISEASE.

PMID- 15446104
TI  - EXPERIENCE IN A SHELTERED WORKSHOP--IS TENSION EQUATED WITH DECREASED
      PRODUCTIVITY?

PMID- 15446105
TI  - WHAT CAN BE DONE FOR CARCINOMA OF THE PANCREAS?

PMID- 15446106
TI  - MEBUTAMATE COMPARED WITH OTHER BASIC ANTIHYPERTENSIVE DRUGS.

PMID- 15446107
TI  - TREATMENT OF FATIGUE IN GENERAL PRACTICE: A DOUBLE BLIND STUDY.

PMID- 15446108
TI  - INDUCTION AND REVERSIBILITY OF GRISEOFULVIN-INDUCED HEPATOMEGALY AND HEPATITIS IN
      MICE.

PMID- 15446109
TI  - THE DIAGNOSTIC ABDOMINAL PARACENTESIS.

PMID- 15446110
TI  - JAMES MONTGOMERY NORTHINGTON, M.D. OCTOBER 11, 1885-JANUARY 15, 1964.

PMID- 15446111
TI  - THE GENERAL PHYSICIAN CAN DIAGNOSE GLAUCOMA.

PMID- 15446112
TI  - A CONTROLLED EVALUATION OF CHLORPHENESIN CARBAMATE IN PAINFUL MUSCULOSKELETAL
      SYNDROMES.

PMID- 15446113
TI  - THE ACTIVITY OF PHOSPHONIC AND PHOSPHINIC ACIDS AGAINST TREPONEMA PALLIDUM.

PMID- 15446114
TI  - OFFICE EVALUATION OF A NEW ANTIHYPERTENSIVE AGENT.

PMID- 15446115
TI  - DIAZEPAM IN THE TREATMENT OF TETANUS: REPORT OF A CASE FOLLOWING TOOTH
      EXTRACTION.

PMID- 15446116
TI  - A CONTROLLED COMPARISON OF THREE MUSCLE RELAXANT AGENTS.

PMID- 15446118
TI  - CIGARETTE SMOKING AND CANCER OF THE LUNG: IS THERE ANY ETIOLOGIC RELATIONSHIP?

PMID- 15446117
TI  - THE DOCTOR AND DISASTER MEDICINE.

PMID- 15446119
TI  - PSYCHOLOGICAL ASPECTS OF THE TREATMENT OF DEPRESSION.

PMID- 15446120
TI  - HYPERCALCEMIA.

PMID- 15446121
TI  - THE PREVENTION OF VIRUS TRANSMISSION WITHIN THE HOSPITAL.

PMID- 15446122
TI  - ASCORBIC ACID AND BENZYLPENICILLIN TOXICITY.

PMID- 15446123
TI  - STUDIES IN LONG TERM DECONGESTANT THERAPY.

PMID- 15446124
TI  - ETIOLOGIC MANAGEMENT OF VAGINITIS.

PMID- 15446125
TI  - CONTROLLED EVALUATION OF PSYCHOTHERAPEUTIC DRUG IN INTERNAL MEDICINE.

PMID- 15446126
TI  - DOCTORS AND THE LAW.

PMID- 15446127
TI  - THE DOCTOR AND HIS FEDERAL INCOME TAX.

PMID- 15446128
TI  - THE DOCTOR BUILDS HIS ESTATE.

PMID- 15446129
TI  - THE MEDICAL TECHNOGRAPHER.

PMID- 15446130
TI  - TREATMENT OF RAGWEED HAY FEVER WITH ALUM PRECIPITATED PYRIDINE COMPLEX EXTRACTS.

PMID- 15446131
TI  - THE PROBLEM AND MANAGEMENT OF NASAL CARRIERS OF STAPHYLOCOCCUS.

PMID- 15446132
TI  - EFFECTIVE APPROACH TO ACNE PROBLEM IN COLLEGE STUDENTS.

PMID- 15446133
TI  - THE USE OF HUMAN BIOASSAY PRINCIPLES IN GENERAL PRACTICE.

PMID- 15446134
TI  - THERMORUBIN, A NEW ANTIBIOTIC FROM A THERMOACTINOMYCETE.

PMID- 15446135
TI  - SULFAMETHOXAZOLE IN THE TREATMENT OF PERSISTENT UROLOGICAL INFECTIONS.

PMID- 15446136
TI  - PARALYTIC ILEUS DUE TO METHOCARBAMOL.

PMID- 15446137
TI  - POSTPARTUM MANAGEMENT OF BOWEL FUNCTION.

PMID- 15446138
TI  - ANKYLOSING SPONDYLITIS WITH SUBCUTANEOUS NODULES.

PMID- 15446139
TI  - DOCTORS AND THE LAW.

PMID- 15446140
TI  - THE DOCTOR AND DISASTER MEDICINE.

PMID- 15446141
TI  - CHANGING TRENDS IN CANCER MORTALITY.

PMID- 15446142
TI  - A TOPICAL ADJUVANT FOR THE TREATMENT OF PSORIASIS.

PMID- 15446143
TI  - TOPICAL BETAMETHASONE IN TREATMENT OF ALLERGIC AND INFLAMMATORY DERMATOSES.

PMID- 15446144
TI  - CARDIAC RESUSCITATION: A PRACTICAL APPROACH.

PMID- 15446145
TI  - THE PROPRIETARY NURSING HOME AND THE PRIVATE PHYSICIAN.

PMID- 15446146
TI  - CLINICAL STUDY IN THE TREATMENT OF ACNE VULGARIS USING ZIRCONIUM AS THE BASE: A
      NEW CONCEPT IN THE CONTROL OF SEBUM EXCRETION.

PMID- 15446147
TI  - TREATMENT OF ACUTE AND CHRONIC MUSCLE SPASM WITH DIAZEPAM.

PMID- 15446148
TI  - DURATION OF BLOOD AND URINARY LEVELS OF CORTICOSTEROID FOLLOWING INTRAMUSCULAR
      INJECTION OF METHYLPREDNISOLONE ACETATE.

PMID- 15446149
TI  - A DOUBLE-BLIND EVALUATION OF ENZYME PREPARATION IN POSTOPERATIVE PATIENTS.

PMID- 15446150
TI  - USE OF CYPROHEPTADINE AND CYPROHEPTADINE-DEXAMETHASONE COMBINATION IN
      DERMATOLOGIC DISORDERS.

PMID- 15446151
TI  - PULMONARY TUBERCULOSIS: A CASE ILLUSTRATING DANGERS OF DELAY IN DIAGNOSIS.

PMID- 15446152
TI  - DOCTORS AND THE LAW.

PMID- 15446153
TI  - THE DOCTOR AND DISASTER MEDICINE.

PMID- 15446154
TI  - DIAGNOSIS AND MANAGEMENT OF MALIGNANT CARCINOID SYNDROME: A REVIEW.

PMID- 15446155
TI  - OCCLUSIVE VASCULAR DISEASE INCLUDING RENAL ARTERY OBSTRUCTION--TREATMENT AND
      PROGNOSIS.

PMID- 15446156
TI  - PENCILLIN HYPERSENSITIVITY.

PMID- 15446157
TI  - ETIOLOGY, SYMPTOMS, AND THERAPY OF ANEMIAS.

PMID- 15446158
TI  - COMPARATIVE EFFECTIVENESS OF GRISEOFULVIN DEPENDING ON CRYSTAL SIZE.

PMID- 15446159
TI  - NOT ALL ARTHRITIS IS RHEUMATOID.

PMID- 15446160
TI  - PIGMENT SHIFTS AFTER USE OF SKIN REFRIGERANTS: A COSMETIC HAZARD OF DERMAL
      CRYOTHERAPY WITH FREON.

PMID- 15446161
TI  - A NEW DEVICE TO AID MOUTH-TO-MOUTH BREATHING.

PMID- 15446162
TI  - TREATMENT OF BRONCHOSPASTIC STATES IN CHILDREN WITH A THEOPHYLLINE-NOSCAPINE
      FORMULATION.

PMID- 15446163
TI  - ANTIPYRETIC EFFECT OF ACETOPHENETIDIN.

PMID- 15446164
TI  - EFFECT OF ZINC BACITRACIN ON THE INCIDENCE OF ENTERITIS AND GROWTH IN YOUNG
      RABBITS.

PMID- 15446165
TI  - PRACTICAL PATHOLOGIC PHYSIOLOGY OF CHRONIC VENOUS INSUFFICIENCY.

PMID- 15446166
TI  - DOCTORS AND THE LAW.

PMID- 15446167
TI  - THE DOCTOR AND DISASTER MEDICINE.

PMID- 15446168
TI  - PERSPECTIVES ON PERSONALITY CONSISTENCY AND CHANGE FROM THE GUIDANCE STUDY.

PMID- 15446169
TI  - REPORT ON PERSONALITY CONSISTENCY AND CHANGE FROM THE FELS LONGITUDINAL STUDY.

PMID- 15446170
TI  - PERSONALITY CONSISTENCY AND CHANGE: AN OVERVIEW OF SOME CONCEPTUAL AND
      METHODOLOGICAL ISSUES.

PMID- 15446171
TI  - CONSISTENCY OF MATERNAL AND CHILD BEHAVIORS IN THE BERKELEY GROWTH STUDY.

PMID- 15446172
TI  - FACTORS IN CONTINUITY AND CHANGE IN THE DEVELOPMENT OF ADAPTATIONAL STYLE IN
      CHILDREN.

PMID- 15446173
TI  - PARATHYROID ADENOMA.

PMID- 15446174
TI  - A COMPARATIVE STUDY OF ERYTHROMYCIN AND TETRACYCLINE IN COMMON BACTERIAL
      INFECTIONS.

PMID- 15446175
TI  - FLUOCINOLONE ACETONIDE IN AN OINTMENT BASE: CLINICAL STUDIES IN SELECTED
      DERMATOSES.

PMID- 15446176
TI  - CLINICAL STUDIES AND THERAPEUTIC USE OF SULFAMETHOXAZOLE IN A PEDIATRIC OUT
      PATIENT CLINIC.

PMID- 15446177
TI  - TREATMENT OF HYPERTENSION WITH GUANETHIDINE AND HYDROCHLOROTHIAZIDE.

PMID- 15446178
TI  - CLINICAL INVESTIGATION FOR MEDICAL PRACTITIONERS. 2. SOME BASIC CONCEPTS.

PMID- 15446179
TI  - THE DOCTOR AND DISASTER MEDICINE.

PMID- 15446180
TI  - THE FAMILIAR FACE.

PMID- 15446181
TI  - LONG TERM USAGE OF NORETHINDRONE WITH MESTRANOL PREPARATIONS IN THE CONTROL OF
      HUMAN FERTILITY.

PMID- 15446182
TI  - PERSONALITY CONSISTENCY AND CHANGE: SOME COMMENTS ON PAPERS BY BAYLEY,
      MACFARLANE, MOSS AND KAGAN, AND MURPHY.

PMID- 15446183
TI  - AN ANALYSIS OF CONSENSUS IN LONGITUDINAL RESEARCH ON PERSONALITY CONSISTENCY AND
      CHANGE: DISCUSSION OF PAPERS BY BAYLEY, MACFARLANE, MOSS AND KAGAN, AND MURPHY.

PMID- 15446184
TI  - USE OF ANABOLIC STEROID, STANOZOLOL, TO PROMOTE WEIGHT GAIN IN UNDERWEIGHT
      PATIENTS.

PMID- 15446185
TI  - STIMULANTS AND TRANQUILIZERS--THEIR USE AND ABUSE.

PMID- 15446186
TI  - THE DIAGNOSIS AND TREATMENT OF NOCTURNAL LEG CRAMPS.

PMID- 15446188
TI  - HEREDITY AND NEOPLASTIC DISEASE.

PMID- 15446187
TI  - THE RATIONALE OF FIBRINOLYSIN THERAPY.

PMID- 15446189
TI  - A STUDY OF THE ANTIPHAGE AND ANTIVIRAL ACTIVITIES OF INDIAN SOIL STREPTOMYCES.
      II. ANTIVIRAL STUDIES.

PMID- 15446190
TI  - USE OF A PLASTIC SPRAY BOTTLE FOR APPLICATION OF NEGATIVE PRESSURE TO NASAL AND
      ACCESSORY SINUS CAVITIES.

PMID- 15446191
TI  - EFFECT OF ANTIBIOTIC DRUGS ON ANTISTAPHYLOCOCCAL ACTIVITY OF LUPULON AND
      HEXAHYDROLUPULON.

PMID- 15446192
TI  - ANTIHYPERTENSIVE THERAPY WITH COMBINED MEBUTAMATE AND HYDROCHLOROTHIAZIDE.

PMID- 15446193
TI  - PALLIATION IN CHRONIC ASTHMATIC BRONCHITIS.

PMID- 15446194
TI  - A LONG RELEASE DOSE FORM OF PENTOBARBITAL COMPARED WITH MEPROBAMATE IN THE
      MANAGEMENT OF ANXIETY STATES.

PMID- 15446195
TI  - DOCTORS AND THE LAW.

PMID- 15446196
TI  - THE DOCTOR AND HIS FEDERAL INCOME TAX.

PMID- 15446197
TI  - CLINICAL INVESTIGATION FOR MEDICAL PRACTITIONERS.

PMID- 15446198
TI  - THE DOCTOR AND DISASTER MEDICINE.

PMID- 15446199
TI  - GOVERNMENT CONTROLLED MEDICINE--FACTS AND FIGURES.

PMID- 15446200
TI  - A NEW TECHNIQUE FOR ASSISTING THE DAMAGED HEART: POSTSYSTOLIC MYOCARDIAL
      AUGMENTATION.

PMID- 15446201
TI  - TREATMENT OF DIAPER RASH WITH AN AEROSOL PRODUCT.

PMID- 15446202
TI  - THE ESTROGEN CANCER MYTH.

PMID- 15446203
TI  - POISONING BY WILD MUSHROOMS.

PMID- 15446204
TI  - EVALUATION OF A NEW HYDROALCOHOLIC BRONCHODILATOR-EXPECTORANT IN ASTHMA.

PMID- 15446205
TI  - THE VALUE OF EMPIRIC THERAPY IN OTITIS EXTERNA.

PMID- 15446206
TI  - CARISOPRODOL IN OSTEOARTHRITIS.

PMID- 15446207
TI  - SPONTANEOUS KIDNEY RUPTURE ASSOCIATED WITH CERVICAL CARCINOMA.

PMID- 15446208
TI  - CLINICAL INVESTIGATION FOR MEDICAL PRACTITIONERS. CHAPTER 4. TRAPS FOR THE
      UNWARY.

PMID- 15446209
TI  - DOCTORS AND THE LAW.

PMID- 15446210
TI  - THE DOCTOR AND DISASTER MEDICINE.

PMID- 15446211
TI  - A CROSS-NATIONAL STUDY OF BUENOS AIRES AND CHICAGO ADOLESCENTS.

PMID- 15446212
TI  - STUDIES ON THE FACTOR STRUCTURE OF INTELLIGENCE IN CHILDREN, ADOLESCENTS, AND
      ADULTS.

PMID- 15446213
TI  - INITIAL EXPLORING OF THE INTELLIGENCE OF SHILLUK CHILDREN. STUDIES IN THE
      SOUTHERN SUDAN.

PMID- 15446214
TI  - PARENTAL ATTITUDES AND BEHAVIORS AS DETERMINANTS OF CHILDREN'S RESPONSES TO THE
      THREAT OF NUCLEAR WAR.

PMID- 15446215
TI  - RELATIONSHIPS BETWEEN RATE OF PHYSICAL  MATURING AND PERSONALITY AMONG BOYS OF
      ITALIAN DESCENT.

PMID- 15446216
TI  - [POSITIVE AND NEGATIVE ATTITUDES AT DIFFERENT AGES].

PMID- 15446217
TI  - LONELINESS, ISOLATION AND SOCIAL RELATIONS IN OLD AGE. A PILOT SURVEY.

PMID- 15446218
TI  - SOCIAL STATUS OF THE AGED IN THREE INDIAN VILLAGES.

PMID- 15446219
TI  - [Vascular development and molecular regulation of angiogenesis during
      tumorigenesis].

PMID- 15446220
TI  - Fear of disclosure and popular stigmas contribute to bad outcomes. CDC finds that
      1 in 5 people stigmatize HIV.
AB  - Two decades into the HIV epidemic, many Americans still are misinformed about how
      HIV is transmitted, and they continue to blame the disease on those who are
      infected, according to a new survey conducted by the Centers for Disease Control
      and Prevention in Atlanta. This widespread stigmatization of the disease and
      those who have it has led some HIV-infected people to delay testing and
      treatment, according to experts. And it affects th way some deal with workplace
      issues. Many HIV-infected workers are afraid to disclose their HIV status, even
      if the disclosure would enable them to seek reasonable accommodations for their
      health issues and treatment.

PMID- 15446221
TI  - How much does the ADA protect workers with HIV? Patients' health care may be at
      risk.
AB  - The Supreme Court's decision is still out on giving workers a clear
      interpretation of their protections under the Americans With Disabilities Act
      (ADA). However, AIDS legal experts say the ADA does offer protection to HIV
      infected workers and these employees should seek reasonable accommodation at
      their workplaces whenever possible and necessary. Despite this seemingly good
      news, there is evidence that at least some HIV-infected patients have postponed
      antiretroviral treatment or taken early leave from their work rather than be
      faced with disclosing their HIV status.

PMID- 15446222
TI  - Here's a look at status of court rulings on ADA. First key decision involved HIV
      infected person.
AB  - The U.S. Supreme Court first issued a decision on HIV and the Americans With
      Disabilities Act (ADA) on June 25, 1998, and for AIDS advocates it was a high
      point in their efforts to provide legal protection to HIV-infected people.
      However, there subsequently have been some disappointing ADA decisions by the
      nation's highest court, and while it's debatable whether these will affect HIV
      patients, it's clear they won't help.

PMID- 15446223
TI  - Prison study shows a transmission first. Finding supports need for consistent
      meds use.
AB  - A study of HIV infection among Texas inmates has identified one patient who was
      infected while in prison and then within one year of infection had acquired nine
      HIV drug mutations, although he had never received antiretroviral treatment.

PMID- 15446224
TI  - When gonorrhea rates rise, can HIV be far behind? CDC's latest STD report notes
      disturbing trend.
AB  - There were at least two significant infectious disease trends in the early 1980s.
      One of those was the advent of HIV infection. The other was the beginning of a
      long decline in gonorrhea rates. Perhaps due in part to the safe-sex practices
      made popular because of the risk of HIV infection, gonorrhea rates continued to
      decline throughout the 1980s and the 1990s until 1999.

PMID- 15446225
TI  - Study: HAART less costly than treatment for AIDS. Annual health care cost lowered
      by 31%.
AB  - Even with the high cost of medications prescribed as part of highly active
      antiretroviral therapy, it's cheaper to treat HIV-infected patients and keep them
      from developing AIDS than it is to take care of them once they have the full
      fledged disease, new research shows.

PMID- 15446226
TI  - Are Native Americans next brush fire in HIV epidemic? The virus has not hit this
      group so far.
AB  - The response of the public and government to rising infection rates among United
      States minority populations, such as African-Americans, may have been a little
      late. The virus had already caused a high rate of infection among this population
      before various groups began focused and consistent prevention and testing
      campaigns.

PMID- 15446227
TI  - Worldwide AIDS statistics offer little reason for optimism. About 26 million
      infected in Africa.
AB  - The latest statistics of world AIDS infections and deaths paint a dismal portrait
      of what life is like on planet Earth during what everyone hopes is the peak of
      the AIDS epidemic. Even what could be seen as good news is not as hopeful as the
      numbers would first appear.

PMID- 15446228
TI  - Russia's HIV epidemic spreads to heterosexuals. UNAIDS coordinator discusses
      current challenges.

PMID- 15446229
TI  - With infection rates rising, will the new administration stay focused on AIDS?
      Activists worry that HIV prevention will be ignored.
AB  - In a banner year for HIV prevention funding from the federal government, the news
      from major epidemic cities on both coasts puts a damper on any back-patting. It
      looks like new HIV infection rates are on the rise again among men who have sex
      with men. AIDS advocates say this means the Bush administration should renew the
      previous administration's focus on HIV prevention funding and make sure it
      remains a priority. Otherwise, middle America may soon see the same increases in
      HIV infection and a simultaneous increase in unsafe sexual behaviors among the
      people who are most at risk of infection.

PMID- 15446230
TI  - San Francisco notes HIV rise in MSM population. About two MSM a day will be newly
      infected in SF.
AB  - It wasn't entirely a surprise given the steep rise in male rectal gonorrhea in
      recent years, but the numbers still are frightening: San Francisco's population
      of men who have sex with men is becoming infected with HIV at a much higher rate
      than four years ago, according to public health data.

PMID- 15446231
TI  - AIDS Foundation makes suggestions to Bush. Guidelines call for more funding, new
      strategies.
AB  - The San Francisco AIDS Foundation wasted no time in letting President Bush know
      what needs to be done about the HIV/AIDS epidemic by sending the President its
      own wish list.

PMID- 15446232
TI  - One-third of HIV patients were not aware of their risk. Should physicians screen
      all patients for HIV?
AB  - HIV testing remains controversial, despite the clear evidence that routine
      testing and early diagnosis can help HIV-infected people receive the medical care
      they need earlier in their disease progression, which could have a positive
      impact on their long-term prognosis.

PMID- 15446233
TI  - Investigators learn how HIV targets the gut. Findings may explain inflammatory
      effects.
AB  - The image of HIV spreading throughout the body rarely conjures up images of a
      person's gut. Yet the gut is one of the primary target sites, perhaps especially
      when a person is infected with HIV through rectal intercourse, oral sex, or
      ingestion of infected breast milk.

PMID- 15446234
TI  - Researchers seek solutions to diarrhea, wasting. Research takes several different
      twists and turns.
AB  - HIV-related diarrhea and cachexia are tremendously serious problems in developing
      countries where there is little access to antiretroviral medications. They also
      remain a concern for many AIDS patients in the United States, yet much needs to
      be proved with regard to treatments.

PMID- 15446235
TI  - Feline research may help address thymic problems. AZT did not stop FIV damage to
      thymus.
AB  - Researchers who have been working with the feline immunodeficiency virus for
      years have concluded that while AZT will stop the virus from multiplying, it does
      not protect the thymus from physical damage.

PMID- 15446236
TI  - Remarks to the article by Pauline Wimberger, Peter Hillemanns, Thomas Kapsner,
      Hermann Hepp and Rainer Kimmig "Evaluation of prognostic factors following flow
      cytometric DNA analysis after cytokeratin labelling: I. Breast cancer" published
      in Analytical Cellular Pathology, Vol. 24, Nos. 4,5 (2002), pp.135-145.

PMID- 15446237
TI  - [Should the RhD prophylaxis be adjusted?].

PMID- 15446239
TI  - [The 77th congress of the Japanese Biochemical Society. Yokohama, Japan. October
      13-16, 2004. Program].

PMID- 15446240
TI  - [The 77th congress of the Japanese Biochemical Society. Yokohama, Japan. October
      13-16, 2004. Abstracts].

PMID- 15446238
TI  - Grafting RGD containing peptides onto hydroxyapatite to promote osteoblastic
      cells adhesion.
AB  - Ceramics possess osteoconductive properties but exhibit no intrinsic
      osteoinductive capacity. Consequently, they are unable to induce new bone
      formation in extra osseous sites. In order to develop bone substitutes with
      osteogenic properties, one promising approach consists of creating hybrid
      materials by associating in vitro biomaterials with osteoprogenitor cells. With
      this aim, we have developed a novel strategy of biomimetic modification to
      enhance osseointegration of hydroxyapatite (HA) implants. RGD-containing peptides
      displaying different conformations (linear GRGDSPC and cyclo-DfKRG) were grafted
      onto HA surface by means of a three-step reaction procedure: silanisation with
      APTES, cross-linking with N-succinimidyl-3-maleimidopropionate and finally
      immobilisation of peptides thanks to thiol bonding. Whole process was performed
      in anhydrous conditions to ensure the reproducibility of the chemical
      functionalisation. The three-step reaction procedure was characterised by high
      resolution X-ray photoelectron spectroscopy. Efficiency of this biomimetic
      modification was finally demonstrated by measuring the adhesion of
      osteoprogenitor cells isolated from HBMSC onto HA surface.

PMID- 15446241
TI  - [Medical teaching in Portuguese colonial India: the creation and earliest decades
      of the new Goa medical-surgical school].
AB  - The centennial celebration of the New Goa Medical -surgical School, held in 1942,
      glorified the institution's contribution to the consolidation of the Portuguese
      Empire in Africa. I observe the School from the perspective of the literature on
      medicine and empire, whose analyzes tend to view it as a tool for exercising
      biopower. I then question this hypothesis from the perspective of primary sources
      on the School's first decades, which paint a picture of frailty and
      administrative disregard that is not very compatible with an imperial project
      engineered to train physicians and disperse them throughout the colonies. I
      conclude that the School's creation stemmed from a process where local interests
      dominated, in a society where the categories "colonizer" and "colonized" were
      diluted within the complexities of social differentiation. It was with the
      twentieth-century rewriting of Portuguese colonial history that the narrative of
      imperial glorification appropriated the School.

PMID- 15446242
TI  - [Abstracts of 52nd Annual Scientific Session of the Japanese College of
      Cardiology. Kyoto, Japan. September 13-15, 2004].

PMID- 15446243
TI  - [The 46th Congress of the Japanese Society of Clinical Hematology. Kyoto, Japan.
      September 17-19, 2004. Program and Abstracts].

PMID- 15446244
TI  - [Febres paulistas and the Sao Paulo society of medicine and surgery: a
      controversy among spokespeople from different arenas of knowledge].
AB  - At the close of the nineteenth century, Sao Paulo physicians were debating a
      disease they classified as "febres paulistas" (Sao Paulo fevers). The article
      present a brief overview of the role of fevers within Brazilian nosology at that
      time and describes how science then explained febres paulistas, malaria, and
      typhoid fever. Changes in the medical field meant febres paulistas were no longer
      classified as forms of malaria but instead considered cases of typhoid fever.
      Following the Society's debates surrounding this shift, the article analyzes the
      scientific lines that tended to identify febres paulistas with malaria or typhoid
      fever and also the line that believed these fevers were an independent
      nosological entity.

PMID- 15446245
TI  - Obituary: Dr. F.P. Antia.

PMID- 15446246
TI  - [Role of the state and municipal orders in the activities of dental service].

PMID- 15446247
TI  - [The drawbacks of the transition from free to paid medical care for patients with
      surgical pathology of maxillofacial region].

PMID- 15446248
TI  - Beyond justice.
AB  - Bioethicists have generally looked after the contractual and fiduciary
      obligations of health care professionals to patients by their adherence to and
      insistence on the principles of ethical action--autonomy, nonmaleficence,
      beneficence, and justice. But these principles, while necessary, only serve the
      best interests of people already recognized as patients. If we truly want to help
      vulnerable populations--those who fall outside the margin--then we need to go
      beyond justice to embrace the theological principles of mercy and grace; that is,
      we need to rely more completely on the way medicine was before secularization and
      commercialism. Competency and compassion intertwine in western medicine.

PMID- 15446249
TI  - [On provision of orthodontic care of aged patients with complete adentia in
      Moscow and the Moscow region].

PMID- 15446251
TI  - [Transformations in curing practices in Rio de Janeiro during the first half of
      the eighteenth century].
AB  - The article analyzes changes in curing practices between 1828 and 1855, mainly in
      Rio de Janeiro. This period saw academic physicians organizing themselves around
      the Faculty of Medicine, the Imperial Academy of Medicine, and specialized
      periodicals, while popular practitioners were simultaneously losing ground in the
      legalization of their activities. The text compares changes in laws and the
      actions of oversight agencies with the activities of non-officialized
      practitioners and the population's reliance on their services. What stands out
      are the conflicts stemming from academic medicine's attempt to gain ascendancy
      over other healing arts, which shows how hard it was for the former to achieve a
      monopoly within therapeutic activities.

PMID- 15446250
TI  - Dehydration and human rights.

PMID- 15446252
TI  - [The doctrine of a wound: from A. V. Vishnevskii to our days].

PMID- 15446253
TI  - [One-stage esophagoplasty with gastric tube in patient undergone suturing of
      esophagus perforation, fundoplication and gastrostomy].

PMID- 15446254
TI  - [Removal of an intramural foreign body of the thoracic part of esophagus].

PMID- 15446255
TI  - [Etiology and pathogenesis of acute pancreatitis].

PMID- 15446256
TI  - [Neoplasms of the cardia. Choice of surgical tactics].

PMID- 15446257
TI  - [Bleedings out of upper parts of gastrointestinal tract after surgeries on
      abdominal organs].

PMID- 15446258
TI  - Medicare program; continuation of Medicare entitlement when disability benefit
      entitlement ends because of substantial gainful activity. Final rule.
AB  - This final rule will conform the existing Medicare eligibility regulations to
      reflect a change made by the Ticket to Work and Work Incentives Improvement Act
      (TWWIIA) of 1999. That statutory change that was implemented effective October 1,
      2000, provides working disabled individuals with continued Medicare entitlement
      for an additional 54 months beyond the previous limit of 24 months, for a total
      of 78 months of Medicare coverage following the 15th month of the reentitlement
      period.

PMID- 15446259
TI  - [Business, politics, science, and visa versa: an institutional history of
      Brazilian medical journalism between 1827 and 1843].
AB  - This analysis of Brazil's first medical newspapers - Propagador das Ciencias
      Medicas (1827-28); Semanario de Saude Publica (1831-33); Diario de Saude (1835
      36); Revista Medica Fluminense (1835-41); Revista Medica Brasileira (1841-43) -
      shows how Rio de Janeiro's socio-cultural context made it possible for this type
      of publication to emerge within the city's dynamic, troubled environment of the
      1820s and 30s. I argue that the distinguishing feature of Brazil's early medical
      journalism was a symbiosis between business (local publishing houses' commercial
      interests), politics (struggles for political hegemony during the consolidation
      of the Imperial State), and science (the movement to institutionalize medicine
      and affirm it as a science).

PMID- 15446260
TI  - [The computer program "Decision matrix" in estimation of individual risk of
      thromboembolic complications in surgical patients].

PMID- 15446261
TI  - [Abdominal aorta prosthesis implantation by minimal access procedure in two weeks
      after surgical treatment of thoracic aorta aneurysm].

PMID- 15446262
TI  - [Diagnosis and surgical treatment of bronchogenic cysts].

PMID- 15446263
TI  - [Observation of non-suture reparation of an open injury of a finger extensor
      tendon at the level of the metacarpal-phalanx joint].

PMID- 15446264
TI  - [A knife wound of the abdomen with simultaneous injury of the portal and inferior
      cava veins].

PMID- 15446265
TI  - [Evolution of methods of surgical treatment of hepatic echinococcosis].

PMID- 15446266
TI  - [Advantages and disadvantages of various methods of cholecystectomy].

PMID- 15446267
TI  - [Men of science in Brazil: colonial empires and the circulation of information
      (1780-1810)].
AB  - In the eighteenth century, the Portuguese imperial model yielded to other
      international strategies, organized according to a logic of networks that
      revolved around centers for the production of knowledge and the creation and
      redistribution of scientific products. Within this context, Portugal underwent a
      'conversion' that drew it towards the French and British colonial systems. A self
      legitimized scientific field was one of the corollaries of the European
      Enlightenment, a process that involved at least two generations of men of science
      and, most importantly, whose success relied on the engagement of the State. This
      process did not transpire systemactically in Brazil, although many of the
      country's men of science were well abreast of the Enlightenment's most modern
      philosophical and scientific theories. Policies to foster scientific activities
      in Brazil did not occur in tandem with broad, deep transformations in the spheres
      of administration, sociability, institutions, economics, or culture.

PMID- 15446268
TI  - [Surgical treatment of injuries of major vessels and their sequelae].

PMID- 15446269
TI  - [The method of non-tension plastic surgery of median postoperative hernias].

PMID- 15446270
TI  - Glycosaminoglycans and the regulation of allergic inflammation.
AB  - Glycosaminoglycans (GAGs) are large, polyanionic molecules expressed throughout
      the body. The GAG heparin, co-released with histamine, is synthesised by and
      stored exclusively in mast cells, whereas the closely related molecule heparan
      sulphate is expressed, as part of a proteoglycan, on cell surfaces and throughout
      tissue matrices. These molecules are increasingly thought to play a role in
      regulation of the inflammatory response and heparin like molecules are now being
      seriously considered to hold potential in the treatment of inflammatory diseases
      such as asthma. Heparin and related molecules have been found to exert anti
      inflammatory effects in a wide range of in vitro assays, animal models and in
      human disease. The anti-inflammatory activities of heparin are independent of the
      well-established anticoagulant activity of heparin, suggesting that the
      separation of these properties could yield novel anti-inflammatory drugs, which
      may be useful in the future treatment of inflammatory diseases.

PMID- 15446271
TI  - Single-molecule dynamics of the calcium-dependent activation of plasma-membrane
      Ca2+-ATPase by calmodulin.
AB  - The plasma membrane calcium-ATPase (PMCA) helps to control cytosolic calcium
      levels by pumping out excess Ca2+. PMCA is regulated by the Ca2+ signaling
      protein calmodulin (CaM), which stimulates PMCA activity by binding to an
      autoinhibitory domain of PMCA. We used single-molecule polarization methods to
      investigate the mechanism of regulation of the PMCA by CaM fluorescently labeled
      with tetramethylrhodamine. The orientational mobility of PMCA-CaM complexes was
      determined from the extent of modulation of single-molecule fluorescence upon
      excitation with a rotating polarization. At a high Ca2+ concentration, the
      distribution of modulation depths reveals that CaM bound to PMCA is
      orientationally mobile, as expected for a dissociated autoinhibitory domain of
      PMCA. In contrast, at a reduced Ca2+ concentration a population of PMCA-CaM
      complexes appears with significantly reduced orientational mobility. This
      population can be attributed to PMCA-CaM complexes in which the autoinhibitory
      domain is not dissociated, and thus the PMCA is inactive. The presence of these
      complexes demonstrates the inadequacy of a two-state model of Ca2+ pump
      activation and suggests a regulatory role for the low-mobility state of the
      complex. When ATP is present, only the high-mobility state is detected, revealing
      an altered interaction between the autoinhibitory and nucleotide-binding domains.

PMID- 15446272
TI  - [Books from the Arco do Cego in colonial Brazil].
AB  - Between 1799 and 1801, the friar Jose Mariano da Conceicao Veloso, a Minas Gerais
      native, headed Lisbon's Casa Literaria do Arco do Cego, which in a brief three
      year span published at least eighty works on topics that included agriculture,
      navigation, and medicine. This editorial project must be understood within the
      context of Dom Rodrigo de Souza Coutinho's enlightened government program. Meant
      to modernize the Empire, it included dissemination of technical and practical
      knowledge in lands under Portuguese dominion, especially in the Americas. As a
      contribution to an understanding of the Enlightenment in Brazil , this article
      presents elements form my research on the development of the project and how it
      was received.

PMID- 15446273
TI  - [Smallpox vaccine: views of the academy of medicine in imperial Brazil].
AB  - In Imperial Brazil, the Academy of Medicine played an important role in promoting
      debates and discussions about local medicine. It was a symbol of the movement to
      try to organize the Brazilian medical body and lend it legitimacy. The article
      focuses on issue surrounding the Academy's activities regarding the smallpox
      vaccine and its conceptions and practice, covering the period form the Academy's
      birth as the Rio de Janeiro Society of Medicine till its transformation into the
      National Academy of Medicine, when Brazil became a Republic at the close of the
      nineteenth century. The main source for this study were the Academy's
      periodicals, which portrayed Brazilian medical thought and practice throughout
      the nineteenth century and underscored the lack of research and the need for
      greater reading on the topic so local studies could be conducted. These
      publications were devoted to disseminating works that had already been published
      in other countries or to discussion raised by Brazilian physicians. The later at
      first targeted clinical and hospital cases and statistics and the later, starting
      in the 1880s, began to incorporate laboratory experiments.

PMID- 15446274
TI  - Measuring progress in Healthy People 2010.
AB  - Background--Healthy People 2010 (HP2010) objectives are based on two overarching
      goals: 1) to increase years and quality of healthy life, and 2) to eliminate
      disparities among subgroups of the population. Four hundred and sixty-seven
      specific objectives consistent with these goals were outlined, baseline data were
      identified when available, and specific targets were set for the year 2010. This
      report discusses the techniques that are being used to measure progress toward
      these two goals. Process--In order to promote consistency in monitoring across
      different objectives, a minimum template of subgroups was adopted for the
      population-based objectives in HP2010. A workgroup of individuals representing
      the U.S. Department of Health and Human Services agencies involved in HP2010 was
      convened to consider the issues related to monitoring progress toward the two
      goals of HP2010. The workgroup concurred with the recommendations in this report.
      Recommendations--Progress toward target attainment can be monitored for all
      objectives with at least one data point beyond the baseline. For those objectives
      that are based on data for a population, progress toward target attainment can
      also be measured for subgroups of the population. Progress toward the elimination
      of disparity for individual population subgroups can be measured in terms of the
      percent difference between each subgroup rate and the most favorable or "best"
      subgroup rate in each domain. For purposes of measuring disparity relative to the
      "best" subgroup rate, all measures are expressed in terms of adverse events.

PMID- 15446275
TI  - [The pathways of the vaccine in nineteenth and twentieth-century Portuguese
      India].
AB  - The article explores the vicissitudes of the nineteenth-century introduction of
      the smallpox vaccine into Portugal's Indian colony of Goa. The choice to use
      smallpox vaccines instead of inoculation evinces local social dynamics and power
      networks that cannot be reduced to a colonizer-colonized duality but that
      interact with scientific issues and techniques imported from Europe and adopted
      locally. Official documents issued by health- service physicians and other
      administrative authorities reveal the actors involved in the fate of the smallpox
      vaccine, raising hypotheses about the motives (involving social, economic,
      technical, and political factors) that shaped their discourse and actions.

PMID- 15446276
TI  - Complications of mandibulotomy.

PMID- 15446277
TI  - A reflection of the coding of meaning in patient-physician interaction: Jurgen
      Habermas' theory of communication applied to sequence analysis.
AB  - This paper introduces parts of Jurgen Habermas' theory of communication in an
      attempt to understand how meaning is coded in patient-physician communication. By
      having a closer look at how patients and physicians make assertions with their
      utterances, light will be shed on difficult aspects of reaching understanding in
      the clinical encounter. Habermas' theory will be used to differentiate assertions
      into validity claims referring to truth, truthfulness and rightness. An analysis
      of hypothetical physician-replies to a patient suffering from back pains will
      substantiate the necessity for such a theory.

PMID- 15446278
TI  - Trouble dead ahead as SHAs pull the PCT levers too hard.

PMID- 15446279
TI  - Trusts ion unequal struggle to cut emergency days.

PMID- 15446280
TI  - [Seeds against smallpox: Joaquim Vas and the scientific translation of bananeira
      brava seeds in Goa, India (1894-1930)].
AB  - In 1914, in the former Portuguese colony of Goa, India, the physician Antonio
      Joaquim Vas announced the discovery of a wonderful treatment for smallpox,
      entailing clinical application of seeds from the bananeira brava (Heliconia biabi
      Sw.m.), a plant remedy allegedly derived from Indian medical practices. The
      present article explores the circumstances surrounding the successes and failures
      of this discovery. The concept of scientific translation is used to interpret the
      transformation of bananeira brava seeds into an early twentieth-century remedy
      for smallpox. This transfer from indigenous use to scientific therapeutic
      constitutes the creation of a quasi-medicine, that is, a case of 'medium
      translation'. Although these seeds occupy a problematic place within the program
      of scientific translation, they enjoyed active circulation within science and
      remained a part of medical practices for combating smallpox.

PMID- 15446281
TI  - The International AIDS Conferences from Vancouver to Bangkok: how far have we
      come in eight years?

PMID- 15446282
TI  - Fallen heroes, lifted hearts: consolation in contemporary Presidential eulogia.
AB  - A.D. Kunkel and M. R. Dennis (2003) demonstrated that examining texts for
      identified components of eulogia, as drawn from the comforting and social support
      paradigms found in psychology and communication literatures (i.e., credibility
      establishment, praise for the deceased, self-disclosure of emotion, prescriptions
      for problem-focused coping, promotion of positive reappraisal for emotion-focused
      coping, and the affirmation and continuation of relationships), is critical to
      understanding eulogistic phenomena. Analysis of three Presidential eulogies, as
      informed by the components, reveals calls for unity in President Ronald Wilson
      Reagan's 1986 eulogy for the Challenger space shuttle crew, suggestions for
      action in President William Jefferson Clinton's 1995 eulogy for USS Cole sailors,
      and positive reappraisal within astronauts' quotes offered by President George
      Walker Bush during his 2003 eulogy for the Columbia space shuttle crew.

PMID- 15446283
TI  - The meaning that young Israeli adults ascribe to the least undesirable death.
AB  - The study examines descriptions by 14 Israeli young adults of the least
      undesirable death. The transcripts of essays and interviews were analyzed by
      phenomenological methods to determine themes and interpret their synthesis into
      the essence of the phenomenon. The least undesirable death was perceived as multi
      dimensional, based on 4 themes: the time, manner, and place in which death
      occurs, and the importance of death being beneficial to others. These themes
      represent 2 salient ideologies in Israeli society: autonomy of the individual
      (including control over his/her own life) and communitarian philosophy that calls
      for emphasis of the common good. These 2 forces, which pull in opposite
      directions, were captured in the essence of the phenomenon: least undesirable for
      self versus least undesirable for others. The results of this study call
      researchers and practitioners in the field of death and dying to move beyond the
      common uni-dimensional perception of a "good death" and to recognize that this is
      a multi-layered phenomenon in which the perspectives of self (autonomy) and
      others (communitarianism) do not necessarily mesh.

PMID- 15446284
TI  - [The role and practices of the curandeiro and saludador in early modern
      Portuguese society].
AB  - This paper will explore the role and practices of magic-using folk healers -
      curandeiros and saludadores - in early modern Portuguese society. The article
      will examine the ambivalent place of the folk healer as a figure both central to
      and marginal in Portuguese popular culture. In considering some of the services
      offered by unlicensed popular healers and their recourse to the unorthodox
      magical means inherent in popular curing, the paper will investigate curandeiros
      and saludadores illicit sources of power. Further, this work will examine the
      prominence of men as folk healers in southern Portugal during the seventeenth and
      eighteenth centuries. Finally, by looking at the notoriety of Luso-African folk
      healers, the paper will assess the importance of race as a factor in the culture
      of Portuguese magical curing.

PMID- 15446285
TI  - Recovery through reconnection: a cultural design for family bereavement in
      Taiwan.
AB  - Using reanalyzed data from ethnographic research performed in Taiwan during the
      1990s, the authors inspect Taiwanese cultural patterns as they affect adaptation
      to loss in the form of death. The data include participant observations and the
      narratives of 52 widows and 30 of their children. An analysis of interview
      transcripts suggests that the most common form of return to a harmony house among
      the participants was achieving a sense of reconnection with the deceased.
      According to the narratives, the Taiwanese concept of reconnection entails (a)
      maintaining the status quo, (b) restoring images of the deceased in family
      affairs, and (c) communicating with the dead. Each theme represents the efforts
      of bereaved families to retain a sense of wholeness (a central Chinese goal) and
      to preserve symbolic images of fathers and husbands. The authors suggest that
      reconnection is a culturally specific and accepted means of resolving grief among
      Taiwanese.

PMID- 15446286
TI  - The factorial structure of the Arabic version of the revised Collett-Lester Fear
      of Death Scale.
AB  - A sample of 209 volunteer Kuwaiti undergraduates responded to an Arabic version
      of the Revised Collett-Lester Fear of Death Scale with 4 subscales: Death of
      Self, Dying of Self, Death of Others, and Dying of Others. Reliabilities of the 4
      subscales and of the grand total score ranged from 0.75 to 0.92, which is
      considered adequate. A 4-factor solution was congruent with the allocation of
      items to 2 subscales (i.e. Dying of Self and Death of Others), whereas the
      theorized factor structure of the other 2 subscales were only partially supported
      by empirical analyses. The intercorrelations between the 4 total subscale scores
      yielded a general factor of death and dying, denoting good factorial validity of
      the scale.

PMID- 15446287
TI  - The factorial structure of the revised Collett-Lester Fear of Death Scale.
AB  - In a study of 144 college students, the factorial structure of the Collett-Lester
      Fear of Death Scale matched the face content of the subscales quite closely,
      ameliorating the criticism of the scale by R. A. Neimeyer et al. (2003).

PMID- 15446288
TI  - Tumor cell resistance to DNA-damaging agents: from apoptosis to neiosis.

PMID- 15446289
TI  - Endocrine-related resources from the National Institutes of Health.

PMID- 15446290
TI  - Patient information page. Polycystic ovary syndrome.

PMID- 15446291
TI  - The HLA-DPB1*0301 marker might predict the requirement for leukotriene receptor
      antagonist in patients with aspirin-intolerant asthma.

PMID- 15446292
TI  - Primary care physicians' approach to food-induced anaphylaxis: a survey.

PMID- 15446293
TI  - Effect of pimecrolimus cream 1% on skin condition and sleep disturbance in
      children with atopic dermatitis.

PMID- 15446294
TI  - Sugar glider allergy: identification of serum specific IgE.

PMID- 15446295
TI  - Effect of topical pimecrolimus on epicutaneous skin testing.

PMID- 15446296
TI  - Recommendations for assigning weights to component tests to derive an overall
      grade.
AB  - BACKGROUND: Performance-based assessments are often not reliable enough to be
      used as the sole method for determining a grade. PURPOSE: Using more than 1
      assessment format has several advantages and can improve the quality of the
      information used to calculate course grades. To achieve a valid and reliable
      total score representing a combination of multiple assessment formats requires
      appropriate weighting procedures. METHODS: The classical test theory rationale
      and methodology for appropriately weighting in-course assessments is presented.
      Two reliablility-related equations are used to make decisions about weighting for
      a computerized performance assessment and a pattern recognition multiple-choice
      exam. RESULTS: Using the equations presented, the outcomes of various weighting
      scenarios are graphically presented. This technique produced weights that allow
      the instructor to obtain acceptable reliability while retaining a substantial
      emphasis on performance assessment. CONCLUSION: The weights assigned to component
      tests used to derive a total score have important reliability and validity
      implications. Course instructors need to consider both empirical reliability and
      logical validity evidence in determining component weights. When used in
      conjunction with classical methods, objectively scored item formats can augment
      performance assessments and enhance overall validity and reliability.

PMID- 15446297
TI  - Effect of religious practices of Ramadan on sleep and perceived sleepiness of
      medical students.
AB  - BACKGROUND: Observant Muslims substantially alter their normal routines,
      including daytime fasting and day-night activity patterns during the month of
      Ramadan. PURPOSE: It is unknown whether observing the religious practices of
      Ramadan impacts negatively on daytime somnolence, a factor known to impair
      learning. METHODS: A cross-sectional survey measuring self-reported sleep time
      and the Epworth Sleepiness Scale of observant Muslim medical students before,
      during, and after Ramadan. RESULTS: There was no significant variation in sleep
      score pre-Ramadan (10.04 +/- 3.47), during Ramadan (10.46 +/- 3.57)m and post
      Ramadan(9.73 +/- 3.33), F(2,355) = 1.278, p = .280. Night sleep hours were
      significantly longer both before (6.22 +/- 1.45) and after (6.22 +/- 1.59) than
      during Ramadan (5.22 +/- 1.85), F(2,366) = 15.289, p < .001. Daytime sleep hours
      pre-Ramadan (1.05 +/- 1.36) and post Ramadan (0.70 +/- 1.21) were significantly
      shorter than during Ramadan (1.48 +/- 1.46; pre: z = 2.654, p = .08; z = -4.940,
      p < .001). CONCLUSION: Students successfully adapt and avoid a rise in daytime
      somnolence by increasing daytime sleep hours during Ramadan.

PMID- 15446298
TI  - Have standardized patient examinations stood the test of time and experience?

PMID- 15446299
TI  - Abstracts of the Canadian Rheumatology Association meeting, February 25-28, 2004,
      Lake Louise, Canada.

PMID- 15446300
TI  - [Progress of the study of determination of folic acid].

PMID- 15446301
TI  - [Dietary nucleotide and its effects on immunity].

PMID- 15446302
TI  - [Advances in the study of pharmacokinetics of volatile organic compounds and its
      uses].

PMID- 15446303
TI  - [Factors influencing immunological failure in rabies vaccine and its preventive
      measures].

PMID- 15446304
TI  - The consensus statement of the Amsterdam Forum on the Care of the Live Kidney
      Donor.

PMID- 15446305
TI  - Human organ and tissue transplantation.

PMID- 15446306
TI  - A role for tumor necrosis factor-alpha-mediated endothelial apoptosis in the
      development of experimental idiopathic pneumonia syndrome.
AB  - BACKGROUND: Idiopathic pneumonia syndrome (IPS) is a frequent and often fatal
      complication of allogeneic bone marrow transplantation (BMT). We have previously
      shown that experimental IPS is associated with alloreactive donor T cells and the
      inflammatory mediators TNF-alpha and lipopolysaccharide. Both TNF-alpha and
      lipopolysaccharide are known contributors to endothelial injury. Although damage
      to vascular endothelia has been associated with other complications after BMT,
      its relationship to lung injury has not been explored. METHODS: We used a well
      established murine BMT system, in which lung injury and graft-versus-host disease
      are induced by minor histocompatibility antigenic differences between donor and
      host, and the DNA terminal transferase nick-end labeling (TUNEL) procedure to
      evaluate whether significant pulmonary vascular endothelial cell (EC) apoptosis
      is present during the development of IPS. RESULTS: Our data demonstrate that
      pulmonary histopathology after allogeneic BMT is accompanied by significant EC
      apoptosis and the appearance of activated caspase 3. Further evaluation reveals
      that EC injury coincides with the onset of pulmonary pathology, is associated
      with elevations in bronchoalveolar lavage fluid tumor necrosis factor (TNF)-alpha
      levels, and is accompanied by evidence for EC activation. Administration of a
      soluble TNF-alpha binding protein (recombinant human TNF-alpha receptor:Fc) from
      week 4 to week 6 after allogeneic BMT significantly reduces EC apoptosis and lung
      histopathology observed in this setting. CONCLUSIONS: EC damage mediated by TNF
      alpha is directly linked to the development of experimental IPS. Methods that
      protect or maintain the integrity of the pulmonary vascular endothelium may
      therefore prove effective in reducing the severity of lung injury after BMT.

PMID- 15446307
TI  - Dynamic of distribution of human bone marrow-derived mesenchymal stem cells after
      transplantation into adult unconditioned mice.
AB  - BACKGROUND: The use of mesenchymal stem cells (MSC) for cell therapy relies on
      their capacity to engraft and survive long-term in the appropriate target
      tissue(s). Animal models have demonstrated that the syngeneic or xenogeneic
      transplantation of MSC results in donor engraftment into the bone marrow and
      other tissues of conditioned recipients. However, there are no reliable data
      showing the fate of human MSC infused into conditioned or unconditioned adult
      recipients. METHODS: In the present study, the authors investigated, by using
      imaging, polymerase chain reaction (PCR), and in situ hybridization, the
      biodistribution of human bone marrow-derived MSC after intravenous infusion into
      unconditioned adult nude mice. RESULTS: As assessed by imaging (gamma camera),
      PCR, and in situ hybridization analysis, the authors' results demonstrate the
      presence of human MSC in bone marrow, spleen, and mesenchymal tissues of
      recipient mice. CONCLUSIONS: These results suggest that human MSC transplantation
      into unconditioned recipients represents an option for providing cellular therapy
      and avoids the complications associated with drugs or radiation conditioning.

PMID- 15446308
TI  - Characterization of the role of major histocompatibility complex in type 1
      diabetes recurrence after islet transplantation.
AB  - BACKGROUND: Major histocompatibility complex (MHC) molecules are essential
      determinants of beta-cell destruction in type 1 diabetes (T1D). MHC class I- or
      class II-null nonobese diabetic (NOD) mice do not spontaneously develop
      autoimmune diabetes and are resistant to adoptive transfer of disease. Both CD4+
      and CD8+ T cells are associated with graft destruction after syngeneic islet
      transplantation. MHC molecules within the graft (i.e., on beta-cells or donor
      lymphocytes) may influence the interactions between antigen presenting cells and
      effector T cells and, therefore, the survival outcome of the graft. METHODS:
      Donor islets from NOD mice deficient in one or both of beta2-microglobulin and
      class II transactivator genes were transplanted into diabetic NOD mice.
      Immunohistochemistry was performed to identify the phenotype of infiltrating
      cells and to assess graft insulin production. The presence of cytokines in the
      grafts was assayed by reverse transcription polymerase chain reaction. RESULTS:
      MHC class II-null islets demonstrated rates of rejection comparable with control
      wild-type (wt) islets. In contrast, MHC class I- and II-null islets demonstrated
      indefinite survival (over 100 days). Infiltrates of both failed and surviving
      grafts were comprised of cytotoxic lymphocytes (CTL), helper T cells, and
      macrophages. Grafts also showed the presence of both Th1- and Th2-type cytokines
      (interleukin [IL]-2, IL-4, IL-10, and interferon-gamma), independent of graft
      status. CONCLUSIONS: These results demonstrate the primary importance of MHC
      class I molecules in the pathogenesis of diabetes recurrence postislet
      transplantation. Conversely, MHC class II expression is not a necessary
      mechanistic component of transplant destruction. In addition, these results
      implicate MHC class I-restricted CTLs but not MHC class II-restricted T cells in
      disease recurrence.

PMID- 15446309
TI  - Beta-galactosidase of ROSA26 mice is a useful marker for detecting the definitive
      erythropoiesis after stem cell transplantation.
AB  - BACKGROUND: Hematopoietic reconstitution after stem cell transplantation has been
      analyzed by using stem cells of Ly5 congenic mice. However, the early
      erythropoiesis has never been analyzed because this marker is not expressed on
      all of the erythroid lineage cells. The transgenic mouse expressing beta
      galactosidase (beta-gal) or green fluorescent protein (GFP) has been reported.
      Using these markers, we analyzed the early erythropoiesis after stem cell
      transplantation. METHODS: The beta-gal activity and GFP were examined in the
      hematopoietic cells of ROSA26 and GFP transgenic mice, respectively, by flow
      cytometry. The primitive hematopoietic stem cell fraction (Lin(-)c-kit(+)Sca
      1(+)) in bone marrow (BM) cells of ROSA26 mice was transferred into lethally
      irradiated mice. The kinetics of hematopoietic reconstitution was analyzed in the
      BM and spleen after transplantation. RESULTS: The beta-gal activity, but not the
      GFP and Ly5, was detected in all of the erythroid (TER119+) cells. The beta-gal
      activity was also detected in the donor-derived myeloid (Mac-1+), B lymphoid
      (B220+), and T lymphoid (Thy-1+) cells in the BM and spleen after stem cell
      transplantation. The kinetics of the hematopoietic reconstitution demonstrated
      that early erythroid (TER119(low)CD71(med)) cells were developed in the BM and
      spleen within 2 days after transplantation before development of proerythroblasts
      (TER119(+)CD71(high)), and that massive erythropoiesis and myelopoiesis were
      observed in the spleen until 2 and 4 weeks after transplantation, respectively.
      Conclusions. The beta-gal of ROSA26 mice can be a useful marker to identify the
      donor-derived hematopoietic cells, including early erythroid cells, and the first
      major wave of erythropoiesis occurring in the spleen after stem cell
      transplantation.

PMID- 15446310
TI  - Paclitaxel prevents loss of pulmonary endothelial barrier integrity during cold
      preservation.
AB  - BACKGROUND: Cold preservation is the most practical method to maintain the
      viability of isolated lungs. However, rapid cooling may affect pulmonary
      endothelial function. We examined the effects of microtubule stabilization with
      paclitaxel on pulmonary endothelial barrier integrity under cold temperature.
      METHODS: Human pulmonary arterial endothelial cells were incubated at 4 degrees C
      for 2 hr in the presence or absence of paclitaxel (2.5 micromol/L). Microtubules
      was visualized using immunocytochemical techniques. Ultrasonic attenuation was
      measured with scanning acoustic microscopy. Endothelial barrier integrity was
      measured as transendothelial electric resistance. In addition, we examined graft
      function in a rat lung transplantation model, in which the donor lung had been
      preserved in the presence of paclitaxel (2.5 micromol/L) at 4 degrees C for 12
      hr. RESULTS: Low temperature caused a reversible microtubule disassembly, but the
      structure of microtubules was preserved by paclitaxel. Paclitaxel prevented the
      cooling-induced decrease in ultrasonic attenuation and transendothelial electric
      resistance. In a rat transplantation model, we found that preservation with
      paclitaxel successfully improved the oxygenation performance of the donor lung,
      which demonstrated only mild congestion and less significant interstitial edema
      without fluid accumulation in the alveolar spaces. CONCLUSIONS: Our results
      indicate that microtubule stabilization with paclitaxel may be beneficial to
      prevent the loss of the endothelial barrier during cold preservation. We conclude
      that the use of paclitaxel in organ preservation solutions is useful in
      protecting pulmonary endothelial barrier integrity during cold preservation,
      thereby reducing the occurrence of early graft failure.

PMID- 15446311
TI  - Donor-derived, liver-specific protein expression after bone marrow
      transplantation.
AB  - BACKGROUND: Bone marrow transplantation (BMT) may represent a novel mechanism to
      deliver a functional gene to a deficient liver. Bone marrow-derived hepatocytes
      are rare and without a defined contribution to liver function. Consequently, the
      clinical significance of BMT to treat liver disease is unclear. We sought to
      quantify bone marrow-derived hepatocyte protein expression after BMT and
      determine whether the process is inducible with liver injury. METHODS: Mice
      transgenic for human alpha-1 antitrypsin (hAAT) under a hepatocyte-specific
      promoter were used as bone marrow donors. Adenoviral transduction of modified
      urokinase plasminogen activator (Ad-muPA) was used to induce liver injury. Eight
      weeks after lethal irradiation and BMT, recipients were stratified into two
      groups: BMT alone (n = 5) and BMT + Ad-muPA (n= 10). Both groups of animals were
      bled before (t = 0) and at 2, 4, 8, and 16 weeks after Ad-muPA administration,
      and the serum samples were assessed for hAAT by enzyme-linked immunosorbent
      assay. RESULTS: Transgenic donor mice expressed 5 to 10 mg/mL of hAAT. Recipients
      of BMT alone expressed less than 80 ng/mL of hAAT over all time periods. Animals
      receiving BMT + Ad-muPA showed sustained and stable hAAT expression of
      approximately 200 ng/mL. Differences were statistically significant at each time
      point. CONCLUSION: Serum protein levels from liver-specific transgene expression
      are detectable and persist after BMT. Expression is low, but inducible with liver
      injury. We are currently developing strategies to augment donor-derived, liver
      specific protein expression after BMT.

PMID- 15446312
TI  - Differences in patient and transplant professional perceptions of
      immunosuppression-induced cosmetic side effects.
AB  - BACKGROUND: A two-part study was initiated to compare kidney transplant patient
      and transplant professional perceptions regarding immunosuppression-related
      physical changes and their impact on transplant recipients. METHODS: Parallel
      surveys were developed and administered to transplant patients and active
      transplant clinicians. RESULTS: Eighty percent of surveyed patients reported
      immunosuppression-induced hirsutism, gingival hyperplasia, acne, alopecia, or
      cushingoid facies. Hirsutism (94%) and gingival hyperplasia (51%) occurred more
      frequently in cyclosporine patients (p < 0.01); alopecia (30%) occurred more
      frequently in tacrolimus patients (p < 0.01). Patient reported incidence of
      physical changes significantly exceeded observations by professionals for every
      condition (p < 0.01), however 84.4% of affected patients reported feeling "happy
      to endure" changes "for the sake of having a transplant." Patients also reported
      emotional and social effects due to physical changes, an outcome underestimated
      by transplant professionals (p < 0.01). Patients and professionals communicated
      about physical changes; however, more than half of affected patients believed
      communication occurred "rarely/never" while over half of the professionals
      believed communication occurred "every visit/most of the time." Although most
      physicians believed changes could be addressed, doctors recommended treatment for
      less than half of the affected patients. When recommended therapy changes were
      pursued, treatments were effective in the majority of cases. CONCLUSIONS:
      Incidence of immunosuppression-related physical changes is high and somewhat
      dependent on drug regimen. Although patients seem willing to accept cosmetic
      changes for the sake of having a transplant, physical changes have a psychosocial
      impact that is underestimated by clinicians. Immunosuppression-related physical
      changes remain underaddressed; effective interventions offer opportunities for
      improved care.

PMID- 15446313
TI  - Hemorrhagic cystitis in children undergoing bone marrow transplantation: a
      putative role for simian virus 40.
AB  - BACKGROUND: Late-onset hemorrhagic cystitis (HC) is a well-known severe
      complication of bone marrow transplantation (BMT), both in adults and in
      children. Protracted postengraftment HC is associated with graft-versus-host
      disease and viral infections, mainly caused by BK virus (BKV) or adenovirus (AV).
      This study investigated whether simian virus 40 (SV40) DNA sequences can be
      detected in specimens from pediatric patients affected by severe postengraftment
      HC. METHODS: The clinical diagnosis of HC was made in 7 of 28 BMT children. DNA
      from peripheral blood mononuclear cells (PBMC) and urine sediment cells and
      supernatants was analyzed by polymerase chain reaction (PCR) for human
      cytomegalovirus (HCMV), AV, BKV, JC virus (JCV), and SV40. DNA filter
      hybridization and sequencing was carried out in SV40-positive samples. RESULTS:
      SV40 footprints were detected in two of seven cases of HC. Specific SV40 DNA
      sequences were detected by PCR and by filter hybridization both in urine and in
      PBMC samples at the HC onset and during the follow-up. The DNA sequencing proved
      that the amplicons belonged to the SV40 wild-type. Urine samples of the two HC
      cases tested negative by cell cultures, PCR, or both for HCMV, BKV, JCV, and AV.
      CONCLUSIONS: The detection of SV40 DNA sequences suggest that this simian
      polyomavirus could be involved, at least in some cases, in the HC occurring in
      children after BMT.

PMID- 15446314
TI  - Isometric tubular epithelial vacuolization in renal allograft biopsy specimens of
      patients receiving low-dose intravenous immunoglobulin for a positive crossmatch.
AB  - BACKGROUND: Perioperative treatment with plasmapheresis and intravenous
      immunoglobulin (IVIG), combined with a tacrolimus-based immunosuppressive
      regimen, has been used successfully to allow renal transplantations in cross
      match-positive recipients. A common finding in biopsy specimens of these
      allografts is isometric vacuolization of proximal tubular epithelium. This
      finding presents a diagnostic dilemma because it may occur secondary to IVIG
      treatment or tacrolimus nephrotoxicity. METHODS: We compared the frequency and
      severity of isometric tubular vacuolization in renal allograft biopsy specimens
      obtained during the first 10 days after transplantation in 24 patients who
      received one or more postoperative treatments with IVIG (100 mg/kg; as part of a
      desensitization protocol also involving plasmapheresis) with specimens obtained
      in 91 patients who did not receive IVIG. All patients received tacrolimus.
      Isometric vacuolization was graded on a 0 to 4 scale based on the fraction of
      proximal tubules involved: 0, none; 1, less than 10%; 2, 10% to 25%; 3, 26% to
      50%; 4, more than 50%. RESULTS: There was a higher frequency of isometric tubular
      vacuolization (71 % vs. 31%) and more widespread involvement in patients who
      received IVIG and tacrolimus versus tacrolimus alone, although mean tacrolimus
      levels were not significantly different between these groups. In control, but not
      IVIG, biopsy specimens, there was a significant association between vacuolization
      score and blood tacrolimus level on the day of biopsy. CONCLUSIONS: Isometric
      tubular vacuolization is a common finding in renal transplant biopsy specimens of
      patients who receive low-dose IVIG and in many cases is likely to be related, at
      least in part, to IVIG. In these patients, this finding should not necessarily be
      interpreted as indicative of tacrolimus (or cyclosporine) nephrotoxicity.

PMID- 15446315
TI  - Calcineurin inhibitor nephrotoxicity: longitudinal assessment by protocol
      histology.
AB  - BACKGROUND: The role and burden of cyclosporine (CsA) nephrotoxicity in long-term
      progressive kidney graft dysfunction is poorly documented. METHODS: The authors
      evaluated 888 prospective protocol kidney biopsy specimens from 99 patients taken
      regularly until 10 years after transplantation for evidence of CsA
      nephrotoxicity. RESULTS: The most sensitive histologic marker of CsA
      nephrotoxicity was arteriolar hyalinosis, predicted by CsA dose and functional
      CsA nephrotoxicity. Striped fibrosis was associated with early initiation of CsA
      and the need for posttransplant dialysis (both P < 0.05). The 10-year cumulative
      Kaplan-Meier prevalence of arteriolar hyalinosis, striped fibrosis, and tubular
      microcalcification was 100%, 88.0%, and 79.2% of kidneys, respectively. Beyond 1
      year, 53.9% had two or more lesions of CsA nephrotoxicity. Structural CsA
      nephrotoxicity occurred in two phases, with different clinical and histologic
      characteristics. The acute phase occurred with a median onset 6 months after
      transplantation, was usually reversible, and was associated with functional CsA
      nephrotoxicity (P < 0.05), high CsA levels (P < 0.05), and mild arteriolar
      hyalinosis (P < 0.001). The chronic phase of CsA nephrotoxicity persisted over
      several biopsies, occurred at a median onset of 3 years, and was associated with
      lower CsA doses and trough levels (both P < 0.05). It was largely irreversible
      and accompanied by severe arteriolar hyalinosis and progressive
      glomerulosclerosis (both P < 0.001). A threshold CsA dose of 5 mg/kg/day
      predicted worsening of arteriolar hyalinosis on sequential histology.
      CONCLUSIONS: Pathologic changes of CsA nephrotoxicity were virtually universal by
      10 years and exacerbated chronic allograft nephropathy. CsA is unsuitable as a
      universal, long-term immunosuppressive agent for kidney transplantation.
      Strategies to ameliorate or avoid nephrotoxicity are thus urgently needed.

PMID- 15446316
TI  - Health status ten years after pediatric liver transplantation--looking beyond the
      graft.
AB  - BACKGROUND: Little is known about long-term health after pediatric orthotopic
      liver transplantation (OLT). This study aimed to characterize the health status
      of recipients 10 years after OLT, with an emphasis on transplant-related
      morbidity and quality of life. METHODS: We performed a retrospective database
      review of 32 children who underwent OLT before October 1992 at one center and
      were alive after 10 years. Outcome measures were assessed 10 years after OLT.
      Cantril's self-anchoring scale was used for global quality of life assessment.
      RESULTS: Synthetic liver function at 10 years was preserved in all patients. The
      annual rate of episodes of acute rejection dropped markedly after the first year
      (1.4 at year 1 to 0.19 rejections/patient/year at year 10). Histologically
      confirmed chronic rejection developed in eight (25%) patients. At 10 years, long
      term complications included mild to severe chronic renal failure (77%), mild
      chronic anemia (59%), and hypertension (25%). Significant growth retardation (z
      score < -2), hyperlipidemia, and diabetes were uncommon. Infection requiring
      hospitalization occurred in 81% of the patients, with varicella zoster virus as
      the most common pathogen. Epstein-Barr virus-related malignancies affected 22% of
      patients. Ten-year survivors perceived quality of life as very good. Self
      reporting of drug nonadherence by seven (22%) adolescents may have contributed to
      development of late onset rejection in this subgroup. Conclusions. Children who
      are 10-year survivors of OLT have excellent graft function and, despite chronic
      extrahepatic morbidities, a self-reported high quality of life.

PMID- 15446317
TI  - Duct-to-duct biliary reconstruction in adult living-donor liver transplantation.
AB  - BACKGROUND: Bile duct-to-duct reconstruction is now used in living-donor liver
      transplantation (LDLT) for adult patients. METHODS: The results of duct-to-duct
      reconstruction were retrospectively analyzed. The subjects were 81 adult patients
      who underwent LDLT at the University of Tokyo Hospital with a follow-up period of
      at least 1 year. The hilar plate of the recipient was dissected to at least the
      second-order branch of the bile ducts. Duct-to-duct anastomosis was performed
      with interrupted sutures, and an external stent tube was inserted from the
      orifice opposite the hilar plate. RESULTS: During the observation period (median,
      664 days), biliary complications were observed in 26 cases (32%). The
      complications included bile juice leakage at the anastomosis or dissection plane
      of the graft in 12 patients, anastomotic stenosis in 10 patients, and tube
      trouble in 6 patients. Two patients had bile juice leakage followed by stenosis.
      Of the 26 patients, 21 required surgical revision. CONCLUSIONS: The current
      technique did not reduce morbidity as expected. Further technical advancement and
      refinement are needed for better results.

PMID- 15446318
TI  - Hepatitis C virus infection with hepatocellular carcinoma: not a controversial
      indication for liver transplantation.
AB  - BACKGROUND: The association of hepatocellular carcinoma (HCC) and chronic
      hepatitis C virus (HCV) infection has been identified as a potential
      contraindication for orthotopic liver transplantation (LT) because of lower
      survival rate compared with other indications. AIM: Evaluate the outcome of
      patients with and without HCC and cirrhosis with and without chronic HCV
      infection undergoing transplantation. Determine the postLT HCC recurrence rate
      and frequency of de novo postLT HCC. PATIENTS AND METHODS: United Network for
      Organ Sharing (UNOS) data was collected from January 1998 to December 2002.
      Cohort included 17,968 patients (11,552 M; 6,416 F) with a mean age of 51 (18-87)
      years. Four groups were established: HCV (n = 7,079), HCC (n = 611), HCV+HCC (n =
      1,078), and no HCV/no HCC (n = 9,200). The overall survival rate was calculated
      at 24 and 48 months postLT. RESULTS: Patient survival at 24 months and 48 months
      was 84% and 75% for HCV, 84% and 68% for HCC, 78% and 72% for HCV+HCC, and 85%
      and 80% for no HCV/no HCC, respectively. Survival at 48 months among the two
      groups was not significantly different (NS). Further analysis of these groups
      revealed a statistically significant advantage in survival at 48 months postLT
      for the no HCV/no HCC group when compared with the HCV group.(P < 0.05) The
      reported rate of postLT HCC recurrence and de novo postLT HCC was 3.3% and 0.05%,
      respectively. CONCLUSION: In this large cohort of U.S. patients, HCC does not
      have an impact on the survival of LT patients infected with HCV.

PMID- 15446319
TI  - Sequential protocols using basiliximab versus antithymocyte globulins in renal
      transplant patients receiving mycophenolate mofetil and steroids.
AB  - BACKGROUND: Sequential anti-thymocyte globulins (ATG)/cyclosporine
      immunosuppression has two main advantages: delayed introduction of the
      nephrotoxic drug cyclosporine and prevention of acute rejection. Basiliximab, a
      recently developed chimeric monoclonal antibody that selectively depletes the
      minor subpopulation of activated T lymphocytes, has been shown to reduce the
      incidence of acute rejection when used with cyclosporine introduced on day 1.
      METHODS: This open, randomized, multicenter study was undertaken to compare the
      safety and efficacy of ATG versus basiliximab induction therapy (IT) with delayed
      introduction of cyclosporine for microemulsion (Neoral) in 105 low immunologic
      risk renal-transplant patients receiving mycophenolate mofetil and steroids.
      RESULTS: One-year patient and graft survival rates were 98.1% and 94.2%,
      respectively, in the basiliximab group (n = 52), and 98.1% and 96.2% in the ATG
      group (n = 53). The incidence of biopsy-confirmed acute rejection was comparable
      (basiliximab 9.6%, ATG 9.4%), as were key parameters of renal function, notably
      serum creatinine levels, time-to-nadir serum creatinine, and the number of
      patients requiring posttransplantation dialysis (basiliximab 28.8%, ATG 30.2%).
      However, significantly fewer patients in the basiliximab group experienced
      cytomegalovirus (CMV) infection, leukopenia, and thrombocytopenia, and this
      without any significant difference in any other key safety parameters (including
      the incidences of serum sickness, fever, lymphoma, and infections in general).
      CONCLUSIONS: Both ATG and basiliximab, when used for IT in a sequential protocol,
      are equally effective in terms of graft and patient survival as well as at
      preventing acute rejection. However, basiliximab is associated with a lower
      incidence of certain key adverse events, namely CMV infection, leukopenia, and
      thrombocytopenia.

PMID- 15446320
TI  - Tacrolimus or cyclosporine: which is the better partner for mycophenolate mofetil
      in heart transplant recipients?
AB  - BACKGROUND: The aim of this single-center study was to investigate whether trough
      level adjusted mycophenolate mofetil (MMF) is more efficacious in combination
      with tacrolimus (TAC) or cyclosporine (CsA) and to evaluate the impact of either
      drug on MMF dosage. METHODS: Sixty patients (TAC, n = 30; CsA, n = 30) undergoing
      heart transplantation were randomized into a prospective, open-label, controlled
      trial. Immunosuppression consisted of TAC or CsA in combination with MMF and
      corticosteroids. Target blood trough levels of TAC, CsA, and mycophenolic acid
      (MPA) were in the range of 10 to 15 ng/mL, 100 to 300 ng/mL, and 1.5 to 4.0
      microg/mL, respectively. Acute rejection episodes (ARE); survival data; and
      adverse events with a special emphasis on infections, diabetes, hypertension,
      hypercholesterolemia, and the development of graft vessel disease (GVD) were
      recorded. RESULTS: Baseline characteristics were well balanced. All patients were
      successfully withdrawn from corticosteroids within 6 months of transplant.
      Freedom from acute rejection was significantly higher (P = 0.0001) and the
      incidence of ARE per 100 patient days significantly lower in the TAC-MMF group
      than in the CsA-MMF group (0.03 vs. 0.15; P = 0.00007). Overall patient survival
      during follow-up was similar (93% vs. 90%). To achieve the targeted MPA blood
      levels, a significantly lower dose of MMF was required for TAC versus CsA
      patients. After a follow-up time of 2 years, the mean GVD score was 1.85 +/- 3.18
      in the TAC-MMF group and 3.95 +/- 4.8 in the CsA-MMF group (P = 0.08).
      CONCLUSIONS: At the selected doses and target levels for TAC and CsA used in this
      study, trough level adjusted MMF was more efficacious in combination with TAC for
      prevention of ARE. Furthermore, CsA patients need significantly more MMF to
      achieve similar MPA levels.

PMID- 15446321
TI  - A donor history of smoking affects early but not late outcome in lung
      transplantation.
AB  - BACKGROUND: Liberalization of tobacco exposure history as an exclusion to lung
      donation has recently occurred to increase donor organ availability. This study
      investigated the effect of donor smoking status and current and cumulative
      cigarette dose on early and late outcomes in lung transplantation. METHODS: From
      1995 to 2002, 173 heart-lung and bilateral single-lung transplant recipients were
      retrospectively reviewed. Seventy-seven (45%) of 173 donors were ever-smokers and
      64 of those 77 were current smokers. These were divided into subgroups by current
      number of cigarettes smoked to investigate acute dose effects and by pack-year to
      investigate cumulative dose effects. Risks of smoking were assessed by univariate
      and multivariate hazard regression models. RESULTS: Univariate analysis revealed
      that there were significant differences between current and cumulative dose
      subgroups in early postoperative variables, including Pao2/Fio2 ratio,
      ventilation time, and intensive care unit stay. Additionally, these variables
      were dose dependent. There was no significant difference in 3-year survival
      between never-smokers and ever-smokers (73% versus 64%, P = 0.27), and a rate of
      decline of survival was similar. There was a trend for the percentage of patients
      dying of bronchiolitis obliterans syndrome to be lower in the ever-smokers group
      compared with the never-smokers group (6% versus 11%, respectively). Multivariate
      analysis revealed current and cumulative smoking as a risk factor for early but
      not late outcomes. CONCLUSIONS: Donor smoking history had a significant effect on
      early outcomes in lung transplantation in a current and cumulative dose-dependent
      fashion. However, no significant effect on late outcomes, including bronchiolitis
      obliterans syndrome, was seen.

PMID- 15446322
TI  - Rapid identification of preformed alloreactive T cells for use in a clinical
      setting.
AB  - BACKGROUND: In clinical practice, HLA matching is generally applied to minimize
      the incidence of graft rejection after transplantation. Recently, graft rejection
      has been directly associated with the presence of preformed alloreactive T cells
      before transplantation. Despite this knowledge, assays to rapidly quantify
      preformed alloreactivity are not available for use in a clinical setting. In this
      study, such an assay was developed and evaluated in a large cohort to correlate
      alloreactive T-cell reactivity with HLA matching. METHODS: Stimulator peripheral
      blood mononuclear cells were prestained with CD45-fluorescein isothiocyanate
      antibody and mixed with responder peripheral blood mononuclear cells. Activation
      induced cytokine secretion was blocked using brefeldin A. After 6 hr,
      functionally active alloreactive responder CD4 and CD8 T cells were quantified
      among fluorescein isothiocyanate-negative cells by their expression of interferon
      gamma on flow cytometry. RESULTS: Directly alloreactive CD4 and CD8 T cells among
      both stimulators and responders were easily distinguished after 6 hr of
      stimulation without being affected by bystander activation. Among 128 paired
      combinations, 23.4% of individuals had alloreactive CD8 T cells, 15.7% had
      alloreactive CD4 T cells, and 12.5% had alloreactivity in both T-cell
      subpopulations. Alloreactive T cells decreased from circulation within a few days
      after transplantation. In line with well-known clinical observations that
      associate HLA matching with graft outcome, the number of HLA-A and -B mismatches
      correlated with alloreactive CD8 T-cell frequencies in the whole study
      population, whereas it did not predict alloreactivity on an individual basis.
      CONCLUSION: Alloreactive T cells may rapidly be quantified after 6 hr of
      stimulation. Thus, the flow cytometric approach may be applied in a clinical
      setting to facilitate the individualization of immunosuppressive therapy and
      studies on the identification of patients who are at increased risk to develop
      graft rejection.

PMID- 15446323
TI  - A mouse model for studying intrahepatic islet transplantation.
AB  - Intrahepatic human islet transplantation has raised hopes for a cure for diabetes
      mellitus, especially in patients with type 1 diabetes; however, the need for a
      substantial amount of islets and, in many instances, repeated transplantations
      demonstrates underlying problems with this procedure, such as failure of
      angiogenesis and immunologic rejection. Studies using rodent models may be
      helpful in improving the success of islet transplantation. However, most of the
      studies using rodents for islet transplantation have been under the kidney
      capsule rather than the liver. Using islets from transgenic mice expressing green
      fluorescent protein under the control of mouse insulin I promoter, the authors
      have developed a method with which to visualize histologic and pathologic changes
      in intraportally transplanted islets and surrounding hepatic tissue using
      reflected light confocal imaging. Initial events 24 hr after islet
      transplantation in the liver include beta-cell loss and hepatic ischemic
      injuries.

PMID- 15446324
TI  - Long-term outcome of sirolimus rescue in kidney-pancreas transplantation.
AB  - Sirolimus (SRL) rescue in kidney-pancreas transplantation has not been well
      described. We reviewed 112 KPTxs performed at our institution between December 3,
      1995 and June 27, 2002. All patients received antibody induction, tacrolimus
      (TAC), mycophenolate mofetil (MMF), and steroids. In 35 patients, SRL was
      substituted for MMF for the following reasons: acute rejection (AR) of kidney or
      pancreas despite adequate TAC levels, MMF intolerance, increasing creatinine
      levels, and TAC-induced hyperglycemia. Three-year kidney and pancreas graft
      survivals were 97% and 90%, respectively. Of 10 patients who were switched to SRL
      because of AR, one kidney failed because of antibody-resistant AR, and one kidney
      developed borderline AR; the other eight patients remain AR-free. AR developed in
      seven other patients despite therapeutic SRL levels; six had TAC levels less than
      4.5 ng/mL. The mean creatinine levels overall and for the group with increasing
      creatinine remained stable. All patients who were switched to SRL for TAC-induced
      hyperglycemia or MMF intolerance improved. Kidney-pancreas transplant recipients
      can be safely switched to SRL with excellent graft and patient survival.

PMID- 15446325
TI  - Single-center study of technical graft loss in 714 consecutive renal transplants.
AB  - No series has specifically focused on rates of technical failure in the kidney
      transplantation operation. We retrospectively examined the incidence of technical
      graft loss in a single kidney transplant program. A total of 714 transplants were
      performed, with a mean follow-up of 3.4 years (range 2-5 years). Technical graft
      loss was defined as graft loss within the first 2 weeks, without evidence of
      allograft rejection. Fourteen patients (2%) demonstrated technical graft loss,
      none of whom received kidneys with multiple renal arteries (n = 106 with multiple
      renal arteries). The incidence of technical graft loss was significantly higher
      in diabetic recipients (4.3% vs. 1.4%, P = 0.03). The mean donor age was
      significantly higher (46.7 vs. 38.1 years, P = 0.05) in patients with technical
      graft loss. We observed that arterial thrombosis seemed to be related to the
      donor (older donor significant risk P = 0.04) and that venous thrombosis seemed
      to be related to the recipient (four of seven patients with positive
      hypercoagulable workup).

PMID- 15446326
TI  - The grafted kidney takes over: disappearance of the nephrotic syndrome after
      preemptive pancreas-kidney and kidney transplantation in diabetic nephropathy.
AB  - This report describes the rapid and complete reversal of proteinuria after
      preemptive transplantation in diabetic nephropathy. Case 1 was a 42-year-old
      woman with type 1 diabetes (before pancreas-kidney graft: serum creatinine 1.6
      mg/dL and proteinuria 9.1 g/day; 1 month after pancreas-kidney graft: proteinuria
      0.3 g/day and creatinine 1.3 mg/dL). Case 2 was a 48-year-old man with type 2
      diabetes (before kidney graft: creatinine 2 mg/dL and proteinuria 5.9 g/day; 1
      month after: proteinuria 0.7 g/day and creatinine 1.1 mg/dL). The proteinuria
      pattern changed (pre: glomerular nonselective, tubular complete; post:
      physiologic). Renal scintiscan (99mTC-MAG3) demonstrated functional exclusion of
      the native kidneys, despite high pretransplant clearance (> 50 mL/min). The
      effect was not linked to euglycemia or readily explainable by pharmacologic
      effects (no difference in renal parameters after pancreas transplantation with
      the same protocols). These data confirm the efficacy of preemptive kidney and
      kidney-pancreas transplantation in diabetic nephrotic syndrome and indicate that
      a regulatory hemodynamic effect should be investigated.

PMID- 15446327
TI  - Cytomegalovirus and heart transplant atherosclerosis: a likely guilt hidden by
      weak proofs.

PMID- 15446328
TI  - Type of induction immunosuppression and posttransplant lymphoproliferative
      disorder.

PMID- 15446329
TI  - [Learning from the interaction].

PMID- 15446330
TI  - [Time for new pictures].

PMID- 15446331
TI  - [Measuring blood pressure: an art in itself. Arm position significantly modifies
      measurement].

PMID- 15446332
TI  - [Systemically oriented interprofessional psychiatric nursing: "Imagine, tonight a
      miracle happens"].

PMID- 15446333
TI  - [Dialectical behavior therapy in borderline syndrome: a way out of the
      therapeutic dead end].

PMID- 15446334
TI  - [Alternative treatment of psychoses: Sotaria--a challenge].

PMID- 15446335
TI  - [Schizophrenia--perspective of family: when the familiar becomes strange].

PMID- 15446336
TI  - [Lavender oil compress: gentle help from blue flowers].

PMID- 15446337
TI  - [Therapeutic touch in pediatric and adolescent psychiatry: hands touching the
      soul].

PMID- 15446338
TI  - [Schulz von Thun communication model: 4 ears are not enough].

PMID- 15446339
TI  - [Day care in the nursing home for patients with dementia: support in a confused
      world].

PMID- 15446340
TI  - [Intervention protocol for preventing psychotic recurrence: detecting warning
      signs early].

PMID- 15446341
TI  - [Presentation of statistical data in nursing. 8--Scatter plots (I): correlations
      become clear].

PMID- 15446342
TI  - [Inpatient nursing care--!: Risks of economic nursing reimbursement].

PMID- 15446343
TI  - [Self- and human knowledge with the Insight Model. Seeing red--engaging the
      brake?].

PMID- 15446344
TI  - [Spiritual dimensions of nursing care--2: The 4 golden truths of Buddha].

PMID- 15446345
TI  - [Suddenly everything is different].

PMID- 15446346
TI  - [Validation in nursing practice: in or out?].

PMID- 15446347
TI  - [Congress for Students in Nursing: the future, that is us!].

PMID- 15446348
TI  - [Adventure in interdisciplinary communication: "Nancy or the dual multi-function
      nurse"--a photo story].

PMID- 15446349
TI  - The effects of outreach on perceived quality of care in two rural areas of
      Bangladesh.
AB  - The 1994 Cairo Conference on Population and Development consensus called for
      actions that will make family planning programmes oriented to the needs and
      concerns of women that are served. This paper, based on data from Bangladesh,
      presents an illustrative analysis of how an outreach programme can be evaluated
      by this criterion. A scale for perceived service quality is developed from five
      indicators of desirable characteristics of services. Regression methods are used
      to assess the impact of outreach service encounters on the perceived quality
      scale. Econometric methods are used to adjust for endogeneity that arises from
      the selectivity of outreach encounters and the selective service exposure of
      contraceptive users. Results show that increasing contact with outreach workers
      increases client satisfaction with the overall quality of the Bangladesh family
      planning programme.

PMID- 15446350
TI  - The risk of child and adolescent mortality among vulnerable populations in Rio de
      Janeiro, Brazil.
AB  - This study investigated the importance of socioeconomic factors such as
      education, income, religion, family structure and residence in explaining the
      increased risk of mortality among vulnerable populations aged less than 20 years
      in Rio de Janeiro, Brazil. Data used were from the 1991 Brazilian Demographic
      Census and comprised 121,060 women aged 15-49 residing in Rio de Janeiro. Two
      alternative statistical methods were used to calculate the risk of death: the
      widely used Brass method (an indirect estimate which assesses population risks)
      and a case-control study (which assesses individual risks). The study also
      focused on the importance of indicators of human and social capital, the lack of
      which may explain the higher risk of death among children and adolescents. Lack
      of education was found to be a major determinant of mortality at young ages.
      Residence in a favela (shantytown), families in which mothers were the head of
      the family, and a lower median level of income were found to be significant
      determinants of mortality among vulnerable populations in Brazil. However,
      religion was not found to be as important a predictor of high mortality.

PMID- 15446351
TI  - Population increases in obesity appear to be partly due to genetics.
AB  - Studies have documented substantial increases in obesity throughout most of the
      industrialized world in recent decades. The majority of explanations for these
      increases have centred around environmental factors such as the increasing
      availability of high-fat, high-carbohydrate foods and sedentary lifestyles. This
      study sought to determine if genetic factors might be contributing to the
      increases in the proportions of North Americans who are obese and overweight. The
      body mass index (BMI) for a large sample of two generations of United States and
      Canadian subjects was correlated with family fertility indicators. Small but
      highly significant positive correlations were found between the BMIs of family
      members and their reproduction rates, especially in the case of women. For
      instance, mothers in the sample (most of whom were born in the 1940s and 50s) who
      were in the normal or below normal range had an average of 4.3 siblings and 3.2
      children, compared with 4.8 siblings and 3.5 children for mothers who were
      overweight or obese. When combined with evidence from twin and adoption studies
      indicating that genes make substantial contributions to obesity, this study
      suggests that recent increases in obesity are partially the result of overweight
      and obese women having more children than is true for average and underweight
      women. It is speculated that improvements in medical treatments for conditions
      associated with obesity--particularly diabetes and heart disease--are making it
      possible for overweight women to live longer and to be more fertile than was true
      historically.

PMID- 15446352
TI  - Month of birth, socioeconomic background and development in Swedish men.
AB  - Season of birth has been shown to correlate with many aspects of somatic and
      mental disorders, development and social adaptation (so-called 'birth-date
      effects'). In a sample of young Swedish men, corresponding roughly to a one-year
      birth cohort, the results of intelligence tests, psychologists' ratings of
      psychological function, school achievement, body height, weight and self-reported
      health during childhood, were found to be correlated with month of birth, and-
      more strongly--father's socioeconomic status. The results were more favourable
      for men who were born during March-May (the period of highest birth rate), and
      whose fathers were of higher socioeconomic status, than for those born in
      November and December (the period of lowest birth rate), and whose fathers were
      in the lower socioeconomic group. It seems reasonable to conclude, from this
      study and previously reported findings, that these so-called 'birth-date effects'
      are determined by varying and often interacting biological and psychosocial
      factors. Among these factors, the light-induced entrainment of circadian and
      annual rhythms in the fetus and/or infant seems to be of pivotal importance. The
      organization of children into one-year age classes therefore produces an unfair
      lack of equality of possibilities.

PMID- 15446353
TI  - Lactational amenorrhoea in well-nourished Toba women of Formosa, Argentina.
AB  - The proximate causes of the contraceptive effect of lactation are still a matter
      of productive debate. This study sought to disentangle the relative impact that
      intense breast-feeding practices and maternal nutrition have on the regulation of
      ovarian function in nursing women. A mixed-longitudinal, direct-observational,
      prospective study was conducted of the return to postpartum fecundity in 113
      breast-feeding, well-nourished Toba women. A sub-sample of 70 women provided data
      on nursing behaviour, daily activities, diet quality and urinary levels of
      oestrone and progesterone metabolites. Well-nourished, intensively breast-feeding
      Toba women experienced a relatively short period of lactational amenorrhoea (10.2
      +/- 4.3 months) and a high lifetime fertility (TFR=6.7 live births/woman).
      Duration of lactational amenorrhoea was not correlated with any of the nursing
      parameters under study or with static measures of maternal nutritional status.
      The results indicated that the pattern of resumption of postpartum fertility
      could be explained, at least partly, by differences in individual metabolic
      budgets. Toba women resumed postpartum ovulation after a period of sustained
      positive energy balance. As the relative metabolic load hypothesis suggests, the
      variable effect of lactation on postpartum fertility may not depend on the
      intensity of nursing per se but rather on the energetic stress that lactation
      represents for the individual mother.

PMID- 15446354
TI  - Adolescent sexuality and the HIV epidemic in Yaounde, Cameroon.
AB  - Adolescents are the focus of many interventions that aim to prevent HIV
      transmission. In order for these interventions to be effective, it is essential
      to understand adolescents' sexual behaviour. Using data collected in Yaounde,
      Cameroon, in 1997, the study analysed risk exposure and HIV prevalence among 426
      men and 510 women aged 15-24. Although risky behaviours seem to be more prevalent
      among young men, their HIV prevalence remains under 1%. In contrast, HIV
      prevalence is high among young women (7.5%), even those who report having had few
      sexual partners. Mixing patterns among sexual partners, and especially the age
      difference between men and women, do not seem to be sufficient to explain the
      large male-female discrepancy in HIV prevalence that is evident in these data.
      The results are therefore probably due to a greater susceptibility to infection
      of young women than men. This study highlights the necessity of reinforcing
      prevention campaigns among youth and fighting the obstacles that continue to
      impede the use of condoms in this population.

PMID- 15446355
TI  - Unintended pregnancy and women's psychological well-being in Indonesia.
AB  - Few studies have examined the impact of unintended pregnancy on women in
      developing countries. This paper examines the impact of unintended pregnancy on
      Indonesian women's psychological well-being. It is hypothesized that experiencing
      unintended pregnancy is associated with lower psychological well-being and that
      use of family planning and small family size are associated with higher levels of
      psychological well-being. Data are drawn from a 1996 survey of 796 women aged 15
      49 from two Indonesian provinces, Lampung and South Sumatra. This article focuses
      on the 71% of women (n=562) who answered all 41 survey items related to
      psychological well-being. In cluster analysis, women grouped into three clusters,
      differentiated by their scores on four scales of well-being established through
      factor analysis (general negative feelings, satisfaction with relationships,
      satisfaction with economic/family/personal conditions, and negative feelings
      regarding domestic issues). Women in cluster 3 were characterized mainly by their
      high level of psychological well-being. Women in cluster 1 had the lowest level
      of well-being, and women in cluster 2 were in the middle. Multinomial logistic
      regression was used to assess jointly the effect of unintended pregnancy,
      contraceptive use, number of children and other factors on a woman's level of
      psychological well-being. Unintended pregnancy was associated with lower levels
      of psychological well-being and contraceptive use was associated with higher
      levels of psychological well-being, while number of children was not associated
      with level of well-being. Women who had experienced an unintended pregnancy were
      less likely to be in the high psychosocial well-being cluster versus both the
      medium and low clusters. In addition, women using contraception were more likely
      to be classified in the high than in the low or medium well-being clusters.

PMID- 15446356
TI  - Depletion of endogenous zinc stores induces oxidative stress and cell death in
      human melanoma cells.
AB  - The role of intracellular free zinc and its chelation by TPEN (N,N,N',N'-
      tetrakis(2-pyridylmethyl)ethylene-diamine) was studied in Bowes human melanoma
      cells. The content of free Zn pools was determined by fluorescent probe Zinquin.
      Depletion of zinc triggered apoptosis confirmed by cell blebbing, changes in
      mitochondrial transmembrane potential and GSH levels, caspase-3 activation and
      nuclear fragmentation. Apoptosis was only partially prevented by cyclosporin A or
      N-acetylcystein, suggesting various independent but likely interrelated
      mechanisms participating in this process.

PMID- 15446357
TI  - Impact of processing on surface structure of human cardiac valve allografts.
AB  - Methods of processing and cryopreservation are believed to be the most important
      factors of long term clinical performance of biological heart valve prostheses.
      That is why we decided to cooperate in evaluating the impact of current AHV
      (allograft heartvalve) bank protocol on valve tissue morphology. AHV harvested
      from "heart-beating" cadaveric donors, considered as a fresh tissue, were
      compared with valve samples from non-heart beating donors, samples stored in
      saline, samples treated with antibiotic solution, and finally with cryopreserved
      valves, stored in liquid nitrogen for months. All samples were dissected, dried
      with hexamethyldisilazane (HMDS) method, gold-coated, studied and photographed in
      scanning electron microscope Tesla BS 301. Different superficial patterns were
      found on ventricular and vascular surfaces of "fresh" semilunar valves. We were
      able to detect early changes of endothelium after harvesting, denudation of
      endothelial covering during preservation with and without freezing. Our
      alternative method of drying samples by HMDS method proved to be suitable for
      thin membranes of human semilunar valves. Scanning electron microscopy seems to
      be helpful for morphological control of processing, cryopreservation and liquid
      nitrogen storage of AHV. We believe that further confrontation of morphological
      investigation with other methods helps us to develop more suitable protocol of
      handling AHV in heart valve banking.

PMID- 15446358
TI  - Does neoplastic cholecystokinin expression reflect the embryonal pattern of the
      protein? A study in human pancreas.
AB  - AIM: To determine the immunoreactivity of cholecystokinin (CCK) during the
      development of the human fetal pancreas and pancreatic adenocarcinoma, given
      that, CCK positive cells were demonstrated either in its embryonic anlage or in
      pancreatic cancer. In order to obtain possible parallels in the expression
      pattern of neoplastic cells in adults (well--moderately--poorly differentiated),
      we investigated the pattern of CCK expression in the pancreatic tissue during the
      various stages of development and compared these with the proliferation of tissue
      assessed by proliferating cell nuclear antigen (PCNA) immunohistochemistry.
      EXPERIMENTAL DESIGN: Tissue sections from 15 pancreatic fetal specimens, and
      equal number of ductal adenocarcinoma specimens, were assessed using
      immunohistochemical methods for CCK. RESULTS: The density of positive cells in
      the primitive exocrine ductal walls and outgrowing buds was significantly higher
      than the relevant density in the neoplastic pancreatic tissue of mixed (ductal
      endocrine) and pure ductal type (p1=0.004, p2 < 0.0005, p3 < 0.0005 and p4=0.023
      respectively). The above values were estimated from 20th to 22nd weeks of
      gestation. There was no significant difference in the density of positive cells
      in the islet cell epithelium from 25-30 weeks, and the neoplastic tissue of mixed
      (p5=0.10) and pure ductal type (p6=0.15). CONCLUSIONS: The immunostaining for CCK
      identifies a sub-group of pancreatic ductal adenocarcinomas with a neuroendocrine
      component (initially considered as pure ductal tumors), and mixed ductal
      endocrine tumors. This pattern of expression in neoplasms recapitulates the
      normal pattern during the embryonal development of the organ, and may be
      important for the development of new therapeutic approaches with eventual
      clinical utility.

PMID- 15446359
TI  - In vitro reactivation of acetylcholinesterase inhibited by cyclosarin using
      bisquaternary pyridinium aldoximes K005, K033, K027 AND K048.
AB  - We have tested four new bisquaternary pyridinium acetylcholinesterase (AChE; EC
      3.1.1.7) reactivators - K005 (1,3-bis(2-hydroxyiminomethylpyridinium) propane
      dibromide), K033 (1,4-bis(2-hydroxyiminomethylpyridinium) butane dibromide), K027
      (1 -(4-hydroxyiminomethylpyridinium)-3-(4-carbamoylpyridinium) propane dibromide)
      and K048 (1-(4-hydroxyiminomethylpyridinium)-4-(4-carbamoylpyridinium) butane
      dibromide) as the potential reactivators of AChE inhibited by cyclosarin. Their
      reactivation potencies were studied using standard in vitro reactivation test.
      Rat brain homogenate was used as the source of the enzyme. Oxime K033 seems to be
      the most potent reactivator of cyclosarin-inhibited AChE. Its reactivation
      potency is significantly higher than the efficacy of all other tested AChE
      reactivators.

PMID- 15446360
TI  - The influence of the time of antidotal treatment administration on its
      effectiveness against tabun-induced poisoning in mice.
AB  - 1. The influence of the time of administration of antidotal treatment consisting
      of anticholinergic drug (atropine) and oxime (pralidoxime, obidoxime, HI-6 or
      trimedoxime) on its effectiveness to eliminate tabun-induced lethal effects was
      studied in mice. 2. The therapeutic efficacy of antidotal treatment of tabun
      induced acute poisoning depends on the time of its administration when obidoxime
      or the oxime HI-6 was used as an acetylcholinesterase reactivator. 3. Pralidoxime
      is practically ineffective to eliminate acute toxic effects of tabun regardless
      of the time of its administration. 4. Our results show that trimedoxime seems to
      be the most effective to eliminate lethal effects of tabun. In addition, its
      efficacy does not decrease when it is administered 5 min after tabun poisoning.
      5. The findings support the hypothesis that trimedoxime appears to be the most
      suitable oxime to counteract acute toxicity of tabun because of its ability to
      eliminate lethal effects of tabun when it is injected 5 min after tabun challenge
      on the contrary to other oximes tested.

PMID- 15446361
TI  - Cyclodextrines as functional agents for decontamination of the skin contaminated
      by nerve agents.
AB  - Three decontamination solutions of beta-cyclodextrines were prepared. Their
      abilities to decontamine rat skin contamined with nerve agent soman were tested.
      Decontamination efficacy of the tested cyclodextrine solutions was compared with
      the same decontamination means but without the cyclodextrines. The efficacy of
      tested decontaminants was evaluated by the assessment of the ID50 values. Two
      decontamination prescriptions with cyclodextrines (tetraborate buffer and
      tetraborate buffer with acetone) do not show significantly better decontamination
      efficacies in comparison with prescriptions without cyclodextrines. Only in case
      of aqueous solution of 2-aminoethanol the addition of beta-cyclodextrine resulted
      in significant increase (32%) in decontamination efficacy.

PMID- 15446362
TI  - Altered intrahepatic hematopoiesis in neonates from women with pregnancy induced
      hypertension/pre-eclampsia.
AB  - AIM: To detect whether preeclampsia influences neonatal intrahepatic
      hematopoiesis, given that an activation of fetal neutrophils and monocytes during
      the course of this disorder occurs. EXPERIMENTAL DESIGN: We examined liver
      samples from 10 neonates of hypertensive/preeclamptic women at 27 to 28 weeks of
      gestation delivered by a cessarian section. All neonates were placed in
      incubators but they all died within 24 hours due to immaturity. The control group
      comprised 10 fetuses of the same gestational age, after voluntary abortion due to
      a neural defect. Specific antibodies against CD34, glycophorin C, hemoglobins A
      and F, myeloperoxidase, CD61, CD68, terminal desoxynucleotidyl transferase and
      the pax-5/B-cell specific activator protein, were used in each sample. RESULTS:
      Neonates from hypertensive/preeclamptic women, in comparison with controls,
      showed: a statistically significant reduction of erythropoiesis by 25% (p=0.015);
      a statistically significant increase of granulopoiesis (p=0.019); a statistically
      significant increase in the expression of CD68 positive cells of the monocytic
      lineage (p=0.017); a statistically significant increase in the expression of CD34
      progenitor/stem positive cells (p=0.021). No statistically significant
      differences were observed in both examined groups, concerning megakaryopoiesis
      and B lymphopoiesis. CONCLUSIONS: Preeclampsia of pregnancy has an impact on
      neonatal intrahepatic hematopoiesis by increasing granulopoiesis, reducing
      erythropoiesis and triggering endothelial and stem cell activation. We suggest
      that these findings reflect a state of persistent inflammation and a loss of red
      blood cell production possibly contributing to the neonatal morbidity related to
      this disorder.

PMID- 15446363
TI  - The detection of urinal neopterin concentration increases the efficiency of
      cervical smear in the diagnosis of cervical cancer.
AB  - OBJECTIVE: To investigate the importance of urinal neopterin detection carried
      out together with cervical smear test, in the diagnosis of cervical cancer.
      METHODS: In this study, urine samples were collected from randomly selected
      vulvovaginitis' women who attended hospital and an independent control group. The
      participants were classified into two representative sample groups and a control
      group; 1st Group: 35 women with vulvovaginitis, whose ages varied from 21 to 42
      and who had no viral infections, and chronic inflammatory diseases and no smoking
      habit, but had complaints of vaginal discharge. 2nd Group: 25 women aged between
      38-52 with no smoking habit, who applied to hospital with complaints of vaginal
      discharge, and cervical cancer was diagnosed for them as the result of biopsy,
      but no associated treatment of cancer had been carried out yet. 3rd Group: A
      control group with 30 women who aged between 20 and 28, with no smoking habit,
      and who had not taken part in sexual activities yet. They had no complaints from
      any type of tumors, and viral infections or chronic inflammatory diseases.
      Urinalysis was carried out for each group member's urine sample in order to
      measure the level of neopterin. Neopterin was estimated by HPLC. Some statistical
      analyses were done by SPSS Windows 10.0 and were analyzed by Oneway Annova test.
      (p=0.000) Meaningful differences between the groups were determined by Post Hoc
      Tukey Test. RESULTS: The mathematical results of neopterin levels for the groups
      revealed that the level of Group 1 was significantly higher than the level of
      Group 3 (p= 0.0001). When the levels of Group 1 and 2 were compared with each
      other, a significant difference was determined (p=0.004). Also, the difference in
      the levels of Group 2 and 3 was found to be significant (p=0.0001). CONCLUSIONS:
      If the results of this study were not confounded by another factor, then we can
      deduce that an increment in the level of neopterin may be considered as a risk
      factor that should warrant further investigation of cervical cancer. Then, the
      detection of urinal neopterin level as a noninvasive test done together with
      cervical smear can increase the sensitivity of smear test.

PMID- 15446364
TI  - Pyrimidine 5'nucleotidase I and II activities in acute leukaemias.
AB  - BACKGROUND AND OBJECTIVE: Pyrimidine 5'nucleotidase I and II activities of
      peripheral mononuclear cells were studied to evaluate their role in diagnosis,
      assessment of therapy and follow up of remission in acute leukaemias. DESIGN AND
      METHODS: Blood samples were obtained from 40 untreated patients with acute
      lymphoblastic and myeloid leukaemia and 40 healthy controls, before the therapy
      and after remission. The correlation between the activity of the enzymes and the
      efficacy of therapy were established. The enzyme activities were measured by High
      Performance Liquid Chromatography (HPLC), using the method described by Amici.
      For statistical analysis, Mann-Whitney U, Kruskal-Wallis and Wilcoxon methods
      were used. RESULTS: Before the therapy, Pyrimidine 5'nucleotidase I levels in the
      leukaemic group were found to be significantly elevated when compared to the
      control group (p<0.001). Also Pyrimidine 5'nucleotidase II levels were
      significantly elevated before the therapy and during remission (p<0.02 and
      p<0.001 respectively). The isoenzyme activities were compared in patients who
      were in remission, who did not respond to therapy and in patients who died during
      the therapy, but no significant difference was found. INTERPRETATION AND
      CONCLUSIONS: We concluded that, Pyrimidine 5'nucleotidase I and II activities can
      be used as markers for diagnosis and follow up of remission in patients with
      acute leukaemia. But, they can not have predictive value for prognosis.

PMID- 15446365
TI  - The angiotensin converting enzyme I/D polymorphism in Turkish athletes and
      sedentary controls.
AB  - The angiotensin converting enzyme (ACE) gene is located on human chromosome 17
      expressing three genotypes within the intron 16 of the related gene structure.
      These genotypes are classified as I and D alleles which are termed as insertion
      and deletion, respectively. This study was carried out to identify possible
      relationships between the insertion/deletion (I/D) polymorphisms and athletic
      performance in Turkish athletes. To be able to determine these relationships,
      eighty healthy athletes and eighty healthy sedentary controls were genotyped for
      the ACE I/D polymorphism at gene level. According to the results obtained, we
      found significant difference on ACE I/D polymorphism in between athletes and
      healthy controls (x2 = 7.32, df = 2, P = 0.026). This result supports the
      association in ACE genotype in Turkish athletes, suggesting that this might be a
      genetic factor influencing the physical performance.

PMID- 15446366
TI  - One-stage maxillary sinus grafting using a modified surgical concept.
AB  - This modified surgical procedure that permits an implantation simultaneously with
      sinus floor elevation procedure even when the original bone is very thin. The
      surgical technique and its benefits were described and discussed.

PMID- 15446367
TI  - Karl Rokitansky: his Bohemian years and his relationship with Jan Evangelista
      Purkyne: on the occasion of bicentenary of birth.
AB  - Karl Rokitansky was born on 19th February 1804 in the historic Czech town of
      Hradec Kralove (Koniggratz). During 1821-1824 he studied for 3 years at the
      medical faculty of Prague University. In the archives of Charles University there
      is a record of Rokitansky's performance during these three years. At the
      university he met J. E. Purkyne who was teaching anatomy at that time.
      Relationship between the two world--renowned medical scientists of Czech origin
      is discussed.

PMID- 15446368
TI  - Failure mode and effects analysis. A hands-on guide for healthcare facilities.
AB  - Failure mode and effects analysis (FMEA) is one method hospitals can use to
      comply with the requirement by the Joint Commission on Accreditation of
      Healthcare Organizations (JCAHO) that they conduct at least one proactive risk
      assessment of a high-risk process each year. While it is not the only means of
      satisfying the requirement, FMEA is an established and widely used procedure and
      is the model suggested by JCAHO. FMEA is not, however, a simple procedure. To
      help our readers better understand the challenges involved, ECRI conducted its
      own FMEA as an exercise. The high-risk process we analyzed was setting up and
      programming infusion pumps for intravenous delivery of medications. In this
      article, we describe each step we carried out, the principles underlying our
      decision making along the way, and the lessons we learned. After reviewing our
      account, the reader should understand what an FMEA is and what it should
      accomplish, know how to choose and define a process for analysis, and grasp the
      key elements of a successful FMEA from start to finish.

PMID- 15446369
TI  - Maintaining life-support and non-life-support equipment. What do JCAHO's new
      requirements mean?
AB  - As part of its new "Shared Visions--New Pathways" initiative, the Joint
      Commission on Accreditation of Healthcare Organizations (JCAHO) now requires
      accredited healthcare facilities to demonstrate that life-support equipment
      receives a high priority in their equipment-maintenance programs. JCAHO has also
      revised its overall accreditation scoring system. Some of our member hospitals
      have asked ECRI for advice on how to deal with these changes. JCAHO's intent, as
      we understand it, is not to impose burdensome new requirements on hospitals, but
      simply to ensure that life-support equipment receives the necessary equipment
      maintenance priority. We believe that any facility that has been meeting JCAHO's
      requirements up to now won't need to significantly change its equipment
      management program, though it will need to revise its documentation procedures.
      In this article, we describe the changes to JCAHO's requirements and outline the
      steps that hospitals need to take to meet the requirements--as well as the steps
      they don't need to take.

PMID- 15446370
TI  - Using blood glucose meters. Minimizing errors, maximizing accuracy.
AB  - Blood glucose meters (BGMs) provide fast and generally accurate measurements of
      the glucose levels of individuals with diabetes. But they aren't foolproof. A
      number of problems can affect BGM accuracy, including technical faults, user
      errors, and variations in patient physiology. An erroneous reading could mean
      that a hypo- or hyperglycemic patient might receive inappropriate therapy or
      perhaps no therapy at all, with potentially life-threatening consequences. In
      this article, we provide recommendations to individuals and healthcare providers
      on ways to minimize erroneous BGM readings. We also offer some troubleshooting
      tips and itemize the physiologic factors that can impact readings--a potential
      source of errors that is often overlooked.

PMID- 15446371
TI  - Hazard report. Medi-Mech supplies the wrong replacement casters for video cart.

PMID- 15446372
TI  - Pulse oximeter accuracy specifications.

PMID- 15446375
TI  - Physiologic and psychologic age-related changes that affect urologic clients.
AB  - Because older adults can present with complex and multiple conditions, geriatrics
      is a truly multidisciplinary field. A review of physiologic and psychologic
      changes associated with aging that may affect urologic clients is presented. The
      implications of these changes to urologic nursing practice are examined.

PMID- 15446376
TI  - Prostate cancer in older men.
AB  - Prostate cancer (Ca P), the most commonly diagnosed male cancer, will be a health
      care issue that will have a significant impact on the American health care system
      as the population of the United States continues to age. It is anticipated that
      the number of men diagnosed with Ca P will continue to increase each year.
      Screening, diagnosis, and treatment modalities for Ca P in men over 65 years of
      age are discussed.

PMID- 15446377
TI  - Being there: the essence of end-of-life nursing care.
AB  - Competent and compassionate end-of-life care is the right of everyone. Nursing
      and the health care profession are obligated to meet this need for their patients
      and provide crucial information and support. Continued efforts must be made to
      increase our knowledge about the normal dying process, symptom management, and
      the role of the interdisciplinary team in supporting patients in their final
      wishes for a "good death".

PMID- 15446378
TI  - Urinary incontinence strategies for frail elderly women.
AB  - Among the majority of frail older women, urinary incontinence has not been
      adequately assessed or treated, with resultant negative impact on quality of
      life. An assessment and intervention model based on type of incontinence,
      evidence-based interventions, and the influence of patient preference and
      capacity to carry out interventions are described.

PMID- 15446379
TI  - Geriatric incontinence: the long-term care challenge.
AB  - Urinary incontinence (UI) is a common but challenging problem in the long-term
      care environment plagued by rising costs, limited resources, and high rates of
      staff turnover. Successful management of incontinence in the nursing home is
      possible but it requires a comprehensive evaluation of the resident and a
      formalized plan of care that is individualized to the resident's unique needs.

PMID- 15446380
TI  - Incontinence products and devices for the elderly.
AB  - Devices and products to contain or collect the urine are part of the management
      of bladder dysfunction, particularly urinary incontinence (UI) (Newman, Bliss, &
      Fader, in press). The aim of continence nurse experts and those who care for
      incontinent individuals during the past decade has been to greatly decrease the
      indiscriminate use of absorbent pads and garments, external collecting devices,
      and indwelling catheterization, through the successful treatment of urinary
      incontinence (UI) with behavioral interventions, drug therapies, and new surgical
      procedures. However, these products and devices can be beneficial for persons who
      are elderly, fail treatment and remain incontinent, who are too ill or disabled
      to participate in behavioral programs, who cannot be helped by medications, or
      who have a type of UI that cannot be alleviated by other interventions (Newman,
      2003). The judicious use of products to contain urine loss and maintain skin
      integrity is a first-line defense for these patients (Fantl et al., 1996).
      Urinary collection devices and products that are appropriate for elderly
      patients, that are used by nurses in all clinical settings, and are available at
      local pharmacies, retail stores, medical equipment dealers or directly from
      manufacturers are discussed.

PMID- 15446382
TI  - Update on immunizations for older adults.

PMID- 15446383
TI  - An introduction to qualitative research methods.

PMID- 15446384
TI  - The geriatric gigglers.

PMID- 15446386
TI  - Infantile spasms: therapy and outcome.
AB  - Up-to date information about corticotropin (ACTH) in the treatment of infantile
      spasms and evaluation of the long-term outcome was provided to answer questions
      about (1) the efficacy of doses of ACTH in comparison with other drugs,
      especially with vigabatrin, and the efficacy in patients with tuberous sclerosis;
      (2) tolerability; and (3) long-term outcome. In two studies, high doses were not
      more effective than low doses but were more effective in another study. In the
      follow-up of the studies, there was no difference. In an open, randomized,
      prospective study, the efficacy and relapse rates of ACTH and vigabatrin
      treatment did not differ significantly. The high response rates in tuberous
      sclerosis complex were similar. Both drugs had severe side effects. In the long
      term follow-up of 20 to 35 years, one third of the patients died, the
      intellectual outcome of the remaining patients was normal or slightly subnormal,
      and one quarter and one third of the patients were seizure free. ACTH should be
      the first choice for treatment of infantile spasms. The side effects of ACTH,
      unlike those of vigabatrin, are well known, treatable, and reversible. However,
      an open, prospective study to compare the efficacy, relapse rate, and long-term
      outcome of treatment with ACTH and vigabatrin is urgently needed. The frequency
      of visual field defects after vigabatrin therapy should be evaluated.

PMID- 15446387
TI  - Neurologic complications of immunization.
AB  - In the United States and many other developed countries, active immunization of
      children has virtually eliminated poliomyelitis, measles, rubella, tetanus, and
      other diseases, such as disease due to Haemophilus influenzae type b. Individual
      vaccines can produce systemic or neurologic reactions ranging from minor events,
      such as pain and erythema at the injection site, to major complications, such as
      seizures, shock, encephalopathy, or death. Immunization programs have also
      generated considerable controversy, as witnessed by recent concerns regarding the
      relationship between vaccines or their constituents and autism or multiple
      sclerosis. This review summarizes current information regarding vaccines, the
      diseases that they prevent, and the potential relationships between vaccines and
      neurologic disease.

PMID- 15446388
TI  - Polymorphisms in xenobiotic metabolism genes and autism.
AB  - Autism is a neurodevelopmental syndrome defined by deficits in social reciprocity
      and communication and by unusual repetitive behaviors. Although there is an
      underlying genetic predisposition, the etiology of autism is currently unknown. A
      recent increase in prevalence suggests that genetically determined vulnerability
      to environmental exposure might contribute to the causation of autism. We
      performed family-based association studies of polymorphisms in metal-regulatory
      transcription factor 1(MTF1), a multispecific organic anion transporter (ABCC1),
      proton-coupled divalent metal ion transporters (SLC11A3 and SLC11A2), paraoxonase
      1 (PON1), and glutathione S-transferase (GSTP1) genes in 196 autistic disorder
      families. There was deviation from the expected pattern of transmission for
      polymorphisms in MTF1 (Single nucleotide polymorphism database reference
      identification number, dbSNP rs3790625, P = .02) and divalent metal ion
      transporter SLC11A3 (dbSNP rs2304704, P = .07) genes. Although these results
      might represent chance finding, further investigations of genetic variations of
      metal metabolism in autism are warranted.

PMID- 15446389
TI  - Clinical, electroencephalographic, and behavioral features of temporal lobe
      epilepsy in childhood.
AB  - This study describes the clinical, electroencephalographic, and behavioral
      features of 36 children with temporal lobe epilepsy. Patients were divided into
      two groups: group A, with 6 patients (< 6 years), and group B, with 30 patients
      (6-18 years). Statistical analysis was performed considering the significance
      level of .05. Regarding the clinical features of the focal seizures, motor
      components were more frequently seen in children younger than 6 years of age (P <
      .01), whereas automatisms were more frequently seen in patients older than 6
      years of age (P < .05). Associated myoclonic seizures were more frequent in the
      younger age group (P < .01). Behavioral disorders such as hyperactivity and
      aggressiveness and speech delay were more common in the younger age group (P <
      .05). Temporal lobe epilepsy in children younger than 6 years of age is more
      frequently associated with motor components, myoclonic seizures, behavioral
      disorders, and speech delay. Conversely, temporal lobe epilepsy in older patients
      has frequent automatisms.

PMID- 15446390
TI  - Intracranial tumors in infants.
AB  - The prognosis in infants with brain tumors has historically been very poor. This
      study reviews 16 infants under the age of 12 months with brain tumors who
      presented to our institution between 1988 and 1999. The aim was to describe the
      clinical presentation, diagnosis, and management of these patients and to
      establish if newer diagnostic and treatment modalities have improved prognosis in
      terms of survival and neurocognitive outcome. Charts were reviewed
      retrospectively for age at diagnosis, time to diagnosis, presenting features,
      location, histology, surgical and adjuvant treatment, survival, and
      neurocognitive outcome. Survival has improved. Three quarters of the patients
      remain alive. The 5-year survival rate was 81%. The 5-year progression-free
      survival rate was 51%, with a median follow-up time of 70 months. The 5-year
      survival rate for benign tumors was 100%. None of the children with malignant
      tumors survived. Morbidity remains high: 8 of 13 survivors had focal neurologic
      deficits, 7 of 13 had epilepsy, and 7 of 12 had significant cognitive disability.
      Future treatment protocols should include formal analysis of neurocognitive
      morbidity, functional outcome, and quality of life measures to provide accurate
      prognostic information and to prepare families for early intervention programs.

PMID- 15446391
TI  - Mercury exposure in children with autistic spectrum disorder: case-control study.
AB  - Although mercury has been proven to be a neurotoxicant, there is a lack of data
      to evaluate the causal relationship between mercury and autism. We aim to see if
      there is increased mercury exposure in children with autistic spectrum disorder.
      We performed a cross-sectional cohort study over a 5-month period in 2000 to
      compare the hair and blood mercury levels of children with autistic spectrum
      disorder (n = 82; mean age 7.2 years) and a control group of normal children (n =
      55; mean age 7.8 years). There was no difference in the mean mercury levels. The
      mean blood mercury levels of the autistic and control groups were 19.53 and 17.68
      nmol/L, respectively (P = .15), and the mean hair mercury levels of the autistic
      and control groups were 2.26 and 2.07 ppm, respectively (P = .79). Thus, the
      results from our cohort study with similar environmental mercury exposure
      indicate that there is no causal relationship between mercury as an environmental
      neurotoxin and autism.

PMID- 15446392
TI  - Antenatal diagnosis of central nervous system anomalies: can we predict
      prognosis?
AB  - Our technical ability to diagnose fetal anomalies of the central nervous system
      by ultrasonography and by fetal magnetic resonance imaging far exceeds our
      current knowledge of their possible neurodevelopmental implications later in
      life. This limitation often makes obstetric and clinical decisions very
      difficult. We retrospectively reviewed the ultrasonographic records of 6220 women
      who had been followed up at two large medical centers between 1994 and 1999. One
      hundred and sixty (2.6%) women had abnormal fetal central nervous system
      findings. The neurodevelopmental outcome of these children was assessed by a
      telephone interview with the parents. Small cerebellar size was the most frequent
      anomaly, followed by isolated mild ventriculomegaly and isolated choroid plexus
      pathology. Suboptimal neurodevelopmental outcome was found in 24% of children
      with isolated ventriculomegaly and in 9% with choroid plexus pathology. In the
      group of children with a "small cerebellum," suboptimal neurodevelopment was
      found in 19%. The measurement of transcerebellar diameter in respect to its
      developmental implication is, to our knowledge, described here for the first
      time. We believe that cerebellar measurements and their possible neurocognitive
      implications should be an integral part of future studies.

PMID- 15446393
TI  - Congenital hypotonia: is there an algorithm?
AB  - This study was performed with the aim of determining the diagnostic profile of
      newborns with hypotonia and of analyzing the usefulness of different procedures
      in the diagnostic process. One hundred thirty-eight hypotonic newborns were
      identified through the search of hospital records in a 10-year period: 121 (88%)
      had central hypotonia and 13 (9%) had peripheral hypotonia, whereas 4 (3%)
      remained unclassified. Analysis of the contribution of clinical data and results
      of investigations led to the construction of an algorithm, by which all cases in
      the group were diagnosed. Step 1, which included clinical data and results of
      examinations, solved 50% of all diagnosed cases. Neuroimaging techniques made up
      step 2 and contributed to the diagnosis in 13%. Step 3 was accomplished by a
      search through Oxford Medical Databases, which yielded the final diagnosis in 9%,
      whereas karyotyping and fluorescent in situ hybridization for Prader-Willi
      syndrome comprised step 4 and contributed to the diagnosis in 6.5%. Biochemical
      tests formed step 5 and contributed to the diagnosis in 6%. Step 6, which
      included specific investigations of muscle and nerve, was diagnostic in 6%. The
      remaining cases (6.5%) were diagnosed only after several follow-up examinations.
      These results could assist the neonatologist when deciding the diagnostic
      approach to floppy newborns.

PMID- 15446394
TI  - Agenesis of the corpus callosum is associated with feeding difficulties.
AB  - Our objective was to characterize the common occurrence of feeding and swallowing
      disorders noticed by our speech therapy department among patients with agenesis
      of the corpus callosum. All patients with suspected or presumed agenesis of the
      corpus callosum undergoing therapy for feeding and/or swallowing disorders,
      including oral and/or pharyngeal dysphagia and oral-sensory disorder, were
      identified. Their brain magnetic resonance imaging (MRI) studies and charts were
      reviewed in detail. Seven patients with striking oral-motor and oral-sensory
      disorder met the criteria for agenesis of the corpus callosum. Particular
      difficulties noted include oral-sensory defensiveness in five of these seven
      patients, oral dysphagia/weakness in all seven patients, and pharyngeal dysphagia
      with risk of aspiration in three of these seven patients. The oral-motor weakness
      observed in all of the patients affected the strength and coordination necessary
      for functional oral-phase swallowing. We conclude that feeding and swallowing
      disorders are significant in children with agenesis of the corpus callosum.
      Although the pathophysiologic mechanism is not known, recognition of this
      phenomenon is important because early detection and intervention can facilitate
      functional feeding and swallowing patterns earlier in these patients, therefore
      avoiding the adverse and more severe disorders that can arise when dysphagias
      and/or oral-sensory disorder persist over extended periods of time.

PMID- 15446395
TI  - Cerebral glycolipidoses: clinical characteristics of 41 pediatric patients.
AB  - A retrospective clinical and biochemical analysis of 41 pediatric patients with
      cerebral lipidoses seen between 1995 to 2003 was performed at a tertiary referral
      center for neurologic disorders in southern India. Enzyme assays in serum and
      leukocytes, including histopathology, neuroimaging, and neurophysiology studies,
      were performed. There were 20 cases of metachromatic leukodystrophy
      (infantile,14; juvenile, 6), 12 cases of Tay-Sachs disease (infantile, 9; late
      G(M2-M3) gangliosidoses, 3), 8 cases of Sandhoff's disease, and 1 male case with
      multiple sulfatase deficiency. Consanguinity was present in 51.2% of cases. The
      male-to-female ratio was 23:17. Similar illness in the families was noted in
      24.4%. The prominent clinical features in sulfatide lipidoses were regression of
      motor and mental milestones, seizures, and speech impairment, and in G(M2)
      gangliosidoses, the features were delayed milestones, startle myoclonus,
      seizures, and the presence of cherry-red spots. The case with multiple sulfatase
      deficiency had low levels of arylsulfatase A and B. This study indicates that
      these autosomal recessive inherited disorders are indeed prevalent in India.

PMID- 15446396
TI  - Elevated pitch perception owing to carbamazepine-activating effect on the
      peripheral auditory system: auditory brainstem response study.
AB  - Auditory disturbance is an uncommon side effect of carbamazepine, the
      pathophysiologic mechanism of which has not been clearly elucidated. We performed
      an auditory brainstem response study in a 9-year-old boy with epilepsy who had
      suffered from falsely higher pitch perception immediately after the start of
      carbamazepine treatment. The auditory brainstem response results showed that both
      the peak latency of wave V and the interpeak latencies of waves I to V were
      significantly prolonged with 85 dB HL click stimulation and that the peak
      amplitudes of the waves were noticeably elevated, particularly with lower click
      stimulation intensity. Although it has been shown that carbamazepine has a
      suppressive effect on the central nervous system, these auditory brainstem
      response findings might constitute evidence of a carbamazepine-activating effect
      on the peripheral auditory system, which probably increased the sensitivity to
      low-pitched sounds, causing the development of falsely higher pitch perception in
      our patient.

PMID- 15446397
TI  - Magnetoencephalographic analysis of rolandic discharges in a patient with
      rolandic epilepsy associated with oromotor deficits.
AB  - The purpose of this study was to clarify the neurophysiologic basis of oromotor
      deficits in a patient with atypical rolandic epilepsy. We investigated
      magnetoencephalographic analysis of rolandic discharges with right predominance
      before and during clonazepam therapy. Before clonazepam administration, current
      sources of rolandic discharges were broadly distributed in the secondary sensory
      cortex, superior temporal gyrus, and parietal association area in addition to
      hand and orofacial division of the primary somatosensory cortex. During
      clonazepam therapy, oromotor deficits were improved, along with a decrease in
      rolandic discharge, and current sources of residual right-sided rolandic
      discharges were shifted to the right superior parietal lobule. Taking the
      clinical course and magnetoencephalographic findings together, the distributed
      rolandic discharge focus might be closely related to oromotor deficits, and
      clonazepam was effective for the disorder.

PMID- 15446398
TI  - Preliminary results for treatments in subacute sclerosing panencephalitis have
      problems?

PMID- 15446399
TI  - Pirkko Santavuori (1933-2004).

PMID- 15446400
TI  - Instant gratification ... not so fast.

PMID- 15446401
TI  - Microcomputed tomographic analysis of the peri-implant bone.
AB  - A recently developed technology allows evaluation of bone biopsies with 3-D
      microcomputed tomography (microCT). The present study evaluated the feasibility
      of application of microCT to the analysis of peri-implant bone tissues. A human
      bone biopsy containing a titanium screw was analyzed using a microCT scan. The
      parameters computed by the microCT were bone volume, bone surface, trabecular
      thickness, trabecular separation, and bone connectivity. Also, the bone-to
      implant apposition was measured, and all results were compared with those
      obtained with standard histomorphometry of the same biopsy. The results of the
      present study suggest that microCT enables 3-D nondestructive evaluation of bone
      biopsies containing endosseous titanium implants, also allowing analysis of the
      bone-implant interface. Measurements of bone-to-implant apposition obtained by
      microCT were similar to those obtained with standard undecalcified histology.

PMID- 15446402
TI  - Human histologic evaluation of an intrabony defect treated with enamel matrix
      derivative, xenograft, and GTR.
AB  - The purpose of the present case report is to clinically and histologically
      evaluate the healing of one advanced intrabony defect following treatment with an
      enamel matrix protein derivative (EMD) combined with a bovine-derived xenograft
      (BDX) and guided tissue regeneration (GTR). One patient with generalized chronic
      periodontitis and one advanced intrabony defect was treated with EMD + BDX + GTR.
      Notches were placed in the root at the level of the calculus and alveolar crest
      to aid histologic identification of new periodontal tissues. Postoperative
      healing was uneventful. At the 7-month histologic examination, healing in the
      intrabony component of the defect was characterized by formation of new
      connective tissue attachment (new cellular cementum with inserting collagen
      fibers) and new bone in the intrabony component. The BDX particles were
      surrounded by bone-like tissue. No direct contact between the graft particles and
      root surface (cementum or dentin) was observed. Healing in the suprabony defect
      component occurred through epithelial downgrowth that stopped at the level of the
      coronal notch. The BDX particles were entirely encapsulated in dense connective
      tissue, without any signs of bone formation. The present case report shows
      formation of new attachment apparatus consisting of new bone, cementum, and
      periodontal ligament in the intrabony component of one human defect treated with
      EMD + BDX + GTR.

PMID- 15446403
TI  - Atrophic mandible reconstruction using calvarial bone grafts and implant
      supported overdentures: radiographic assessment of autograft healing and
      adaptation.
AB  - Bone grafting constitutes a vital surgical procedure in the management of
      severely atrophic mandibles. In this regard, calvarial bone autografts are
      applied in the reconstruction of wide mandibular defects caused by edentulousness
      and long-term denture-related resorption. Grafts are used as a framework to
      augment the residual ridge and provide implant stability for further prosthetic
      restoration. On the basis that radiographic evidence corresponds to biologic
      changes in bone response to transplantation and loading, the goal of this article
      is to document the radiographic assessment of calvarial autologous bone grafts in
      the recipient site. Panoramic radiographs were used to evaluate bone changes
      occurring during both the graft healing period and graft adaptation after implant
      loading. Emerging data show that conventional panoramic radiography may have an
      effect on the investigation of bone grafts and provide initial information about
      graft incorporation and adaptation.

PMID- 15446404
TI  - Clinical and laboratory steps for the fabrication of a fixed, cement-retained,
      implant-supported, complete-arch maxillary prosthesis.
AB  - The fabrication of a complete-arch maxillary prosthesis has been associated with
      several prosthetic complications and difficulties. Although it has been reported
      that phonetics, esthetics, and proper lip support are difficult to achieve, there
      is a scarcity of literature on the clinical and laboratory procedures necessary
      to minimize these complications. The current article provides clinical and
      laboratory steps that may enable the clinician to achieve more predictable
      restorative results when fabricating a cement-retained, implant-supported,
      complete-arch maxillary prosthesis.

PMID- 15446405
TI  - Hard and soft tissue augmentation in implant therapy using acellular dermal
      matrix.
AB  - The use of acellular dermal matrix to correct soft and hard tissue defects
      involving implants is described through three case reports. Correction of a ridge
      deformity caused by a root fracture, submerging of an existing implant and
      correction of recession defects around adjacent teeth, and ridge preservation for
      implant placement are presented. The use of acellular dermal matrix prevented the
      need for a second surgical site for donor material and the possible attendant
      postoperative complications. It also enhanced patient comfort and satisfaction
      with the procedure. All three cases demonstrated excellent functional and
      esthetic results for both the patients and professionals involved in the therapy.

PMID- 15446406
TI  - Clinical evaluation of an enamel matrix derivative and a bioresorbable membrane
      in the treatment of degree III mandibular furcation involvement: a series of nine
      patients.
AB  - The present study evaluated the effect of combining an enamel matrix derivative
      (EMD) and a bioresorbable membrane (GTR) in the surgical treatment of degree III
      mandibular furcation involvements. Nine patients with chronic periodontitis,
      presenting a total of 14 degree III mandibular furcation involvements, were
      included in the study. Surgical treatment of the defects was randomly assigned:
      (1) EMD (four defects); (2) GTR (three defects); and (3) EMD and GTR (seven
      defects). The degree of involvement was assessed prior to surgery and after 6 and
      12 months by measuring the probing attachment level in the horizontal and
      vertical directions at the furcation site. At 6 and 12 months, partial closure of
      the involvements had occurred in approximately half of the treated furcations,
      and the vertical probing level consistently improved following all three
      treatment modalities. The results suggest that all three treatment modalities may
      improve healing following surgical treatment of degree III mandibular furcation
      involvements. However, further studies are needed to examine the clinical
      significance of these results and the histologic characteristics of the healing
      following application of EMD.

PMID- 15446407
TI  - Comparison of the effectiveness of scaling and root planing in vivo using hand vs
      rotary instruments.
AB  - The purpose of the present investigation was to compare the effectiveness of a
      scaling bur and conventional Gracey curettes in vivo. Ten teeth scheduled for
      extraction were scaled and root planed thoroughly before extraction. The
      instrumented areas were observed using SEM. Scaling with a No. 12 fluted carbide
      bur was more effective in removing debris and plaque than were conventional
      Gracey curettes. Because of the aggressive nature of the process, a certain
      learning curve is necessary to get accustomed to bur scaling; otherwise, dentinal
      hypersensitivity and patient discomfort may be increased.

PMID- 15446408
TI  - Gingival augmentation with an acellular dermal matrix: human histologic
      evaluation of a case--placement of the graft on periosteum.
AB  - The goal of this case report is to evaluate the effectiveness of gingival
      augmentation with an acellular dermal matrix. The acellular dermal matrix was
      placed on a periosteal bed. Clinically, the procedure did not result in an
      increase in the amount of keratinized tissue. There was an increase in the tissue
      bulk, but the importance of this increase is unknown. Histologic evaluation
      revealed that the acellular dermal matrix did not slough and was involved in
      healing. Based on this evaluation, the technique of placing an acellular dermal
      matrix on a periosteal bed does increase the bulk of tissue in the area. However,
      the procedure does not seem to be an effective method to increase the amount of
      keratinized tissue.

PMID- 15446409
TI  - Dimensions of the dentogingival unit in maxillary anterior teeth: a new
      exploration technique (parallel profile radiograph).
AB  - This study sought to develop and evaluate a radiographic exploration technique
      (parallel profile radiograph [PPRx]) for measuring the dentogingival unit on the
      buccal surfaces of anterior teeth, and to provide additional information on the
      dimensions of the dentogingival unit in humans. In 88 periodontally healthy
      individuals, a PPRx was made of the maxillary left central incisor. Over these
      images, the components of the dentogingival unit were measured. PPRx was a highly
      reproducible exploratory technique. Mean dentogingival measurements on the buccal
      surfaces of the teeth were 2.05 +/- 0.87 mm for distance between the CEJ and bone
      crest; 2.00 +/- 0.72 mm for biologic width; 1.75 +/- 0.24 mm for thickness of
      connective tissue attachment; 1.12 +/- 0.24 mm for thickness of free gingiva at
      its base; 0.45 +/- 0.20 mm for thickness of bone plate at crest level; and 1.41
      +/- 0.62 mm for gingival overlap on enamel surface. A statistically significant
      relationship was observed between free gingival width and thickness of connective
      attachment, and the depth of the gingival sulcus. These results corroborate the
      notion that the dimensions of the dentogingival unit are highly variable in
      humans. The thicknesses of both the connective tissue attachment and free
      gingiva, however, showed less variability than did the thickness of the bone
      crest, distance between CEJ and bone crest, and biologic width. The results
      suggest that gingival dimensions are correlated to dentogingival unit dimensions.

PMID- 15446411
TI  - [Some general pathological and biological categories: health, disease,
      homeostasis, sanogenesis, adaptation, immunity. New approaches and definitions].
AB  - The article outlines new approaches to definition of categories of homeostasis,
      health, disease and sanogenesis in terms of relationships between human body and
      environment. According to these definitions, health is the state of the body with
      unaffected functional dynamic homeostasis securing optimal functioning for
      productive relations with the environment; disease is the state of the body with
      affected functional dynamic homeostasis and its inability to accomplish functions
      for productive relations with the environment. These formulations reflect
      biological and social aspects of the above categories.

PMID- 15446412
TI  - [The role of hematopoietic microenvironment in prodigiozan' mechanism of action
      on postradiation recovery of hemopoiesis in long-term bone marrow cultures].
AB  - Influence of prodigiozan in different concentrations on the process of
      postirradiation recovery of haemopoietic precursors (GM-CFC) and morphologically
      recognizable elements of the bone marrow were studied in long-term bone marrow
      cultures during 28 days after 2 Gy gamma-irradiation. Also, prodigiozan was
      studied for action on the contents of GM-CFC and induction of GM-CSF three, 24
      and 48 hours after injection in cultures unexposed to radiation. It is shown that
      injection of prodigiozan in concentration 0.1-1.0 microg/ml 24 hours prior to
      irradiation stimulates postradiation recovery of GM-CFC number and a total number
      of myelocaryocytes in irradiation of long-term bone marrow cultures. In saved
      cultures there was an increase in the number of stromal cells 1 and 2 days after
      radiation. In non-exposed to radiation long-term bone marrow cultures injection
      of prodigiozan increased induction of GM-CSF and raised contents of GM-CFC. The
      maximal increase occurred 24 hours after introduction of radioprotector. It is
      suggested that one of the mechanisms of a radioprotective action of prodigiozan
      may be stimulation of hematopoietic microenvironment cellular elements leading to
      a marked release of GM-CSF or/and other cytokines and stimulation of recovery of
      hemopoietic precursors.

PMID- 15446413
TI  - [The influence of the actoprotectors on lipid peroxidation and erythrocyte
      membranes in rats poisoned with malathion ].
AB  - Actoprotecting properties ofbemitil, tietasol in combination with atropin were
      studied in red cell membranes and lipid peroxidation of rats poisoned with MI in
      a dose 320 mg/kg (0.9 LD50). Atropin treatment showed a low effect. The addition
      of bemitil and tietasol normalized electric charge and osmotic resistance in red
      cell membranes, activity of superoxide dismutase, catalase, glucose-6-phosphate
      dehydrogenase and content of lipid peroxidation products--ketodienes and TBA
      reacting products. Efficacy of the combined treatment is due primarily to
      noncholinergic mechanism of action of bemitil and tietasol--stimulation of
      endogenic antioxidant systems of erythron and antiradical activity (bemitil).

PMID- 15446414
TI  - [Antiarrhythmic and cardioprotective effect of stimulation of delta1-opiate
      receptors in myocardial ischemia and reperfusion].
AB  - Pretreatment with intravenous peptide delta1-opioid receptor (OR) agonist DPDPE
      (0.5 mg/kg) decreases the incidence of occlusion (10 min) and reperfusion (10
      min) arrhythmias in rats. The agonist of delta2-OR DSLET has no effect on
      arrhythmias in coronary artery occlusion and reperfusion. Pretreatment with
      selective delta-antagonists ICI 174,864 (2.5 mg/kg) eliminates an antiarrhythmic
      effect of DPDPE. The addition of DPDPE to the perfusion solution in a final
      concentration of 0.1 mg/l and/or 0.5 mg/l fifteen min before ischemia also
      decreases the incidence of reperfusion arrhythmias in a concentration-dependent
      manner. The addition of DPDPE to the perfusion solution in a final concentration
      of 0.1 mg/l decreases creatine kinase levels in the coronary sinus effluent.
      However, DPDPE has no cardioprotective effect in a concentration of 0.5 mg/l or
      after intravenous administration. It is suggested that antiarrhythmic and
      cardioprotective effects of DPDPE during reperfusion may be due to stimulation of
      cardiac delta1-receptors.

PMID- 15446415
TI  - [Endorphin component of endogenic opioid system: location, reception, function].

PMID- 15446416
TI  - [Clinical, pathophysiological and morphological features of closed craniocerebral
      trauma in combatants].
AB  - We studied clinicodynamic features of neuropsychic disorders resultant from a
      combat craniocerebral trauma (CCT) in patients of Nizhny Novgorod Regional
      Neurological Hospital for War Veterans (n = 420). The patients were divided into
      three groups: with mild, moderate and severe traumas. All the patients were
      examined clinically and clinicophysiologically (electroencephalography, computer
      tomography, electrocardiography, ultrasound and X-ray investigations).
      Experimental-psychological tests and questionnaire survey were alsom conducted.
      200 patients had been followed up for 3-7 years. Impairment of brain stem
      structures and vascular factor play a key role in development of
      psychopathological disorders of primary asthenic and neurosis-like spectrum.
      Local lesion of the brain in severe CCT leads to predominant manifestations of
      the psychoorganic syndrome in milder symptoms of poststress disorders.

PMID- 15446417
TI  - [Urgent problems of experimental modelling of thermal skin burns].
AB  - The review presents a critical analysis of principal benefits and shortcomings of
      standard experimental models of surface and deep thermal burns of the skin.
      Comparison of the results of experimental studies must rest on reproduction of
      identical traumas in series of experiments. It is important to choose animals
      species, burn model, exposition time and thermal agent depending on the study
      aim. An algorithm of simple and available methods of reproduction of superficial
      and deep thermal burns of the skin on a rodent model is described.

PMID- 15446419
TI  - Evolution and stability of the G-matrix on a landscape with a moving optimum.
AB  - In quantitative genetics, the genetic architecture of traits, described in terms
      of variances and covariances, plays a major role in determining the trajectory of
      evolutionary change. Hence, the genetic variance-covariance matrix (G-matrix) is
      a critical component of modern quantitative genetics theory. Considerable debate
      has surrounded the issue of G-matrix constancy because unstable G-matrices
      provide major difficulties for evolutionary inference. Empirical studies and
      analytical theory have not resolved the debate. Here we present the results of
      stochastic models of G-matrix evolution in a population responding to an adaptive
      landscape with an optimum that moves at a constant rate. This study builds on the
      previous results of stochastic simulations of G-matrix stability under
      stabilizing selection arising from a stationary optimum. The addition of a moving
      optimum leads to several important new insights. First, evolution along genetic
      lines of least resistance increases stability of the orientation of the G-matrix
      relative to stabilizing selection alone. Evolution across genetic lines of least
      resistance decreases G-matrix stability. Second, evolution in response to a
      continuously changing optimum can produce persistent maladaptation for a
      correlated trait, even if its optimum does not change. Third, the retrospective
      analysis of selection performs very well when the mean G-matrix (G) is known with
      certainty, indicating that covariance between G and the directional selection
      gradient beta is usually small enough in magnitude that it introduces only a
      small bias in estimates of the net selection gradient. Our results also show,
      however, that the contemporary G-matrix only serves as a rough guide to G. The
      most promising approach for the estimation of G is probably through comparative
      phylogenetic analysis. Overall, our results show that directional selection
      actually can increase stability of the G-matrix and that retrospective analysis
      of selection is inherently feasible. One major remaining challenge is to gain a
      sufficient understanding of the G-matrix to allow the confident estimation of G.

PMID- 15446420
TI  - Epistasis and the temporal change in the additive variance-covariance matrix
      induced by drift.
AB  - The effect of population bottlenecks on the components of the genetic covariance
      generated by two neutral independent epistatic loci has been studied
      theoretically (additive, covA; dominance, covD; additive-by-additive, covAA;
      additive-by-dominance, covAD; and dominance-by-dominance, covDD). The additive-by
      additive model and a more general model covering all possible types of marginal
      gene action at the single-locus level (additive/dominance epistatic model) were
      considered. The covariance components in an infinitely large panmictic population
      (ancestral components) were compared with their expected values at equilibrium
      over replicates randomly derived from the base population, after t consecutive
      bottlenecks of equal size N (derived components). Formulae were obtained in terms
      of the allele frequencies and effects at each locus, the corresponding epistatic
      effects and the inbreeding coefficient Ft. These expressions show that the
      contribution of nonadditive loci to the derived additive covariance (covAt) does
      not linearly decrease with inbreeding, as in the pure additive case, and may
      initially increase or even change sign in specific situations. Numerical examples
      were also analyzed, restricted for simplicity to the case of all covariance
      components being positive. For additive-by-additive epistasis, the condition
      covAt > covA only holds for high frequencies of the allele decreasing the metric
      traits at each locus (negative allele) if epistasis is weak, or for intermediate
      allele frequencies if it is strong. For the additive/dominance epistatic model,
      however, covAt > covA applies for low frequencies of the negative alleles at one
      or both loci and mild epistasis, but this result can be progressively extended to
      intermediate frequencies as epistasis becomes stronger. Without epistasis the
      same qualitative results were found, indicating that marginal dominance induced
      by epistasis can be considered as the primary cause of an increase of the
      additive covariance after bottlenecks. For all models, the magnitude of the ratio
      covAt/covA was inversely related to N and t.

PMID- 15446421
TI  - Application of Johnson et al.'s speciation threshold model to apparent
      colonization times of island biotas.
AB  - Understanding patterns of diversity can be furthered by analysis of the dynamics
      of colonization, speciation, and extinction on islands using historical
      information provided by molecular phylogeography. The land birds of the Lesser
      Antilles are one of the most thoroughly described regional faunas in this
      context. In an analysis of colonization times, Ricklefs and Bermingham (2001)
      found that the cumulative distribution of lineages with respect to increasing
      time since colonization exhibits a striking change in slope at a genetic distance
      of about 2% mitochondrial DNA sequence divergence (about one million years). They
      further showed how this heterogeneity could be explained by either an abrupt
      increase in colonization rates or a mass extinction event. Cherry et al. (2002),
      referring to a model developed by Johnson et al. (2000), argued instead that the
      pattern resulted from a speciation threshold for reproductive isolation of island
      populations from their continental source populations. Prior to this threshold,
      genetic divergence is slowed by migration from the source, and species of varying
      age accumulate at a low genetic distance. After the threshold is reached, source
      and island populations diverge more rapidly, creating heterogeneity in the
      distribution of apparent ages of island taxa. We simulated of Johnson et al.'s
      speciation-threshold model, incorporating genetic divergence at rate k and
      fixation at rate M of genes that have migrated between the source and the island
      population. Fixation resets the divergence clock to zero. The speciation
      threshold model fits the distribution of divergence times of Lesser Antillean
      birds well with biologically plausible parameter estimates. Application of the
      model to the Hawaiian avifauna, which does not exhibit marked heterogeneity of
      genetic divergence, and the West Indian herpetofauna, which does, required
      unreasonably high migration-fixation rates, several orders of magnitude greater
      than the colonization rate. However, the plausibility of the speciation
      divergence model for Lesser Antillean birds emphasizes the importance of further
      investigation of historical biogeography on a regional scale for whole biotas, as
      well as the migration of genes between populations on long time scales and the
      achievement of reproductive isolation.

PMID- 15446422
TI  - The phylogeny of a species-level tendency: species heritability and possible deep
      origins of Bergmann's rule in tetrapods.
AB  - One of the most widely recognized generalizations in biology is Bergmann's rule,
      the observation that, within species of birds and mammals, body size tends to be
      inversely related to ambient temperature. Recent studies indicate that turtles
      and salamanders also tend to follow Bergmann's rule, which hints that this
      species-level tendency originated early in tetrapod history. Furthermore,
      exceptions to Bergmann's rule are concentrated within squamate reptiles (lizards
      and snakes), suggesting that the tendency to express a Bergmann's rule cline may
      be heritable at the species level. We evaluated species-level heritability and
      early origination of Bergmann's rule by mapping size-latitude relationships for
      352 species onto a tetrapod phylogeny. When the largest available dataset is
      used, Bergmann's rule shows significant phylogenetic signal, indicating species
      level heritability. This represents one of the few demonstrations of heritability
      for an emergent species-level property and the first for an ecogeographic rule.
      When species are discretely coded as showing either Bergmann's rule or its
      converse, parsimony reconstructions suggest that: (1) the tendency to follow
      Bergmann's rule is ancestral for tetrapods, and (2) most extant species that
      express the rule have retained this tendency from that ancient ancestor. The
      first inference also generally holds when the discrete data or size-latitude
      correlation coefficients are analyzed using maximum likelihood, although the
      results are only statistically significant for some versions of the discrete
      analyses. The best estimates of ancestral states suggest that the traditional
      adaptive explanation for Bergmann's rule-conservation of metabolic heat-was not
      involved in the origin of the trait since that origin predates the evolution of
      endothermy. A more general thermoregulatory hypothesis could apply to endotherms
      and some ectotherms, but fails to explain why salamanders have retained
      Bergmann's rule. Thus, if thermoregulation underlies the origin of a Bergmann's
      rule tendency, this trait may have been continuously maintained while its cause
      changed. Alternatively, thermoregulation may not underlie Bergmann's rule in any
      tetrapod group. The results also suggest that many extinct groups not included in
      our analyses followed Bergmann's rule.

PMID- 15446423
TI  - Evolution of mixed strategies of plant defense allocation against natural
      enemies.
AB  - In this study we present a simple optimization model for the evolution of
      defensive strategies (tolerance and resistance) of plants against their natural
      enemies. The model specifically evaluates the consequences of introducing
      variable costs and benefits of tolerance and resistance and nonlinear cost-and
      benefit functions for tolerance and resistance. Incorporating these assumptions,
      the present model of plant defense predicts different evolutionary scenarios, not
      expected by previous work. Basically, the presence of an adaptive peak
      corresponding to intermediate levels of allocation to tolerance and resistance
      can arise when the shape parameter of the cost function is higher than the
      corresponding of the benefit function. The presence of two alternatives peaks of
      maximum tolerance and maximum resistance occurs only when benefits of tolerance
      and resistance interact less than additive. Finally, the presence of one peak of
      maximum resistance or maximum tolerance depends on the relative values of the
      magnitude of costs for tolerance and resistance. An important outcome of our
      model is that under a plausible set of conditions, variable costs of tolerance
      and resistance can represent an important aspect involved in the maintenance of
      intermediate levels of tolerance and resistance, and in favoring adaptive
      divergence in plant defensive strategies among populations. The model offers a
      framework for future theoretical and empirical work toward understanding spatial
      variation in levels of allocation to different defensive strategies.

PMID- 15446424
TI  - Population variation in the cost and benefit of tolerance and resistance against
      herbivory in Datura stramonium.
AB  - In this study we examine the hypothesis that divergent natural selection produces
      genetic differentiation among populations in plant defensive strategies
      (tolerance and resistance) generating adaptive variation in defensive traits
      against herbivory. Controlled genetic material (paternal half-sib families) from
      two populations of the annual Datura stramonium genetically differentiated in
      tolerance and resistance to herbivory were used. This set of paternal half-sib
      families was planted at both sites of origin and the pattern of genotypic
      selection acting on tolerance and resistance was determined, as well as the
      presence and variation in the magnitude of allocational costs of tolerance.
      Selection analyses support the adaptive differentiation hypothesis. Tolerance was
      favored at the site with higher average level of tolerance, and resistance was
      favored at the site with higher average level of resistance. The presence of
      significant environmentally dependent costs of tolerance was in agreement with
      site variation in the adaptive value of tolerance. Our results support the
      expectation that environmentally dependent costs of plant defensive strategies
      can generate differences among populations in the evolutionary trajectory of
      defensive traits and promote the existence of a selection mosaic. The pattern of
      contrasting selection on tolerance suggests that, in some populations of D.
      stramonium, tolerance may alter the strength of reciprocal coevolution between
      plant resistance and natural enemies.

PMID- 15446425
TI  - Evolution of genome size in pines (Pinus) and its life-history correlates:
      supertree analyses.
AB  - Genome size has been suggested to be a fundamental biological attribute in
      determining life-history traits in many groups of organisms. We examined the
      relationships between pine genome sizes and pine phylogeny, environmental factors
      (latitude, elevation, annual rainfall), and biological traits (latitudinal and
      elevational ranges, seed mass, minimum generation time, interval between large
      seed crops, seed dispersal mode, relative growth rate, measures of potential and
      actual invasiveness, and level of rarity). Genome sizes were determined for 60
      pine taxa and then combined with published values to make a dataset encompassing
      85 species, or 70% of species in the genus. Supertrees were constructed using 20
      published source phylogenies. Ancestral genome size was estimated as 32 pg.
      Genome size has apparently remained stable or increased over evolutionary time in
      subgenus Strobus, while it has decreased in most subsections in subgenus Pinus.
      We analyzed relationships between genome size and life-history variables using
      cross-species correlations and phylogenetically independent contrasts derived
      from supertree constructions. The generally assumed positive relation between
      genome size and minimum generation time could not be confirmed in
      phylogenetically controlled analyses. We found that the strongest correlation was
      between genome size and seed mass. Because the growth quantities specific leaf
      area and leaf area ratio (and to a lesser extent relative growth rate) are
      strongly negatively related to seed mass, they were also negatively correlated
      with genome size. Northern latitudinal limit was negatively correlated with
      genome size. Invasiveness, particularly of wind-dispersed species, was negatively
      associated with both genome size and seed mass. Seed mass and its relationships
      with seed number, dispersal mode, and growth rate contribute greatly to the
      differences in life-history strategies of pines. Many life-history patterns are
      therefore indirectly, but consistently, associated with genome size.

PMID- 15446426
TI  - Comparative population genetic structures and local adaptation of two mutualists.
AB  - Similar patterns of dispersal and gene flow between closely associated organisms
      may promote local adaptation and coevolutionary processes. We compare the genetic
      structures of the two species of a plant genus (Roridula gorgonias and R.
      dentata) and their respective obligately associated hemipteran mutualists
      (Pameridea roridulae and P. marlothi) using allozymes. In addition, we determine
      whether genetic structure is related to differences in host choice by Pameridea.
      Allozyme variation was found to be very structured among plant populations but
      less so among hemipteran populations. Strong genetic structuring among hemipteran
      populations was only evident when large distances isolated the plant populations
      on which they live. Although genetic distances among plant populations were
      correlated with genetic distances among hemipteran populations, genetic distances
      of both plants and hemipterans were better correlated with geographic distance.
      Because Roridula and Pameridea have different scales of gene flow, adaptation at
      the local population level is unlikely. However, the restricted gene flow of both
      plants and hemipterans could enable adaptation to occur at a regional level. In
      choice experiments, the hemipteran (Pameridea) has a strong preference for its
      carnivorous host plant (Roridula) above unrelated host plants. Pameridea also
      prefers its host species to its closely related sister species. Specialization at
      the specific level is likely to reinforce cospeciation processes in this
      mutualism. However, Pameridea does not exhibit intraspecific preferences toward
      plants from their natal populations above plants from isolated, non-natal
      populations.

PMID- 15446427
TI  - Adaptation to temperate climates.
AB  - Only model organisms live in a world of endless summer. Fitness at temperate
      latitudes reflects the ability of organisms in nature to exploit the favorable
      season, to mitigate the effects of the unfavorable season, and to make the timely
      switch from one life style to the other. Herein, we define fitness as Ry, the
      year-long cohort replacement rate across all four seasons, of the mosquito,
      Wyeomyia smithii, reared in its natural microhabitat in processor-controlled
      environment rooms. First, we exposed cohorts of W. smithii, from southern,
      midlatitude, and northern populations (30-50 degrees N) to southern and northern
      thermal years during which we factored out evolved differences in photoperiodic
      response. We found clear evidence of evolved differences in heat and cold
      tolerance among populations. Relative cold tolerance of northern populations
      became apparent when populations were stressed to the brink of extinction;
      relative heat tolerance of southern populations became apparent when the adverse
      effects of heat could accumulate over several generations. Second, we exposed
      southern, midlatitude, and northern populations to natural, midlatitude day
      lengths in a thermally benign midlatitude thermal year. We found that evolved
      differences in photoperiodic response (1) prevented the timely entry of southern
      populations into diapause resulting in a 74% decline in fitness, and (2) forced
      northern populations to endure a warm-season diapause resulting in an 88% decline
      in fitness. We argue that reciprocal transplants across latitudes in nature
      always confound the effects of the thermal and photic environment on fitness.
      Yet, to our knowledge, no one has previously held the thermal year constant while
      varying the photic year. This distinction is crucial in evaluating the potential
      impact of climate change. Because global warming in the Northern Hemisphere is
      proceeding faster at northern than at southern latitudes and because this change
      represents an amelioration of the thermal environment and a concomitant increase
      in the duration of the growing season, we conclude that there should be more
      rapid evolution of photoperiodic response than of thermal tolerance as a
      consequence of global warming among northern, temperate ectotherms.

PMID- 15446428
TI  - Sexual selection in the gift-giving dance fly, Rhamphomyia sulcata, favors small
      males carrying small gifts.
AB  - In some species of insects males transfer a gift to females during courtship or
      copulation. In the dance flies these nuptial gifts vary from nutritious prey
      items to inedible tokens such as a leaf, stone, or silk balloon. Nuptial gifts in
      dance flies are presumed to increase male mating success. We examined the
      strength and form of sexual selection on male Rhamphomyia sulcata, an empidid in
      which males provide females with a nutritious prey item as a nuptial gift. We
      found that whereas large males carried large gifts, neither large males nor gifts
      were targets of sexual selection. Indeed, correlational selection analysis and
      nonparametric examination of the fitness surfaces revealed that small males
      carrying small gifts were the most successful. Males may be more maneuverable or
      flight efficient with small gifts, or small males with large gifts may be unable
      to carry both a large gift and a female in the paired descent flight. These
      results suggest carrying constraints may be an important factor in determining
      selection on nuptial gift size. The largest target of sexual selection was old
      males. Old males were also paired with the largest and most fecund females,
      highlighting the role mate quality can further contribute to selection on males.
      Correlational selection analysis also revealed selection for an increase in
      covariance between male wing length and body size, and for an increase in slope
      between these traits. Males who deviate away from the optimal phenotypic
      relationship for two tightly related morphological traits, such as tibia and wing
      length, may have overall reduced performance. These findings highlight the role
      correlational sexual selection can play in optimizing nonsexual male morphology
      and scaling relationships. This study questions the role of the nuptial gift in
      dance flies as a resource for females.

PMID- 15446429
TI  - Constraints on evolution and postcopulatory sexual selection: trade-offs among
      ejaculate characteristics.
AB  - Ejaculates function as an integrated unit to ensure male fertility and paternity,
      can have a complex structure, and can experience multiple episodes of selection.
      Current studies on the evolution of ejaculates typically focus on phenotypic
      variation in sperm number, size, or related traits such as testes size as
      adaptations to postcopulatory male-male competition. However, the evolution of
      the integrated nature of ejaculate structure and function depends on genetic
      variation in and covariation between the component parts. Here we report a
      quantitative genetic study of the components of the ejaculate of the cockroach
      Nauphoeta cinerea, including those we know to experience postcopulatory sexual
      selection, in the context of functional integration of ejaculate characters. We
      use the patterns of genetic variation and covariation to infer how the
      integration of the functions of the ejaculate constrain and shape its evolution.
      Ejaculate components were highly variable, showed significant additive genetic
      variance, and moderate to high evolvability. The level of genetic variation in
      these characters, despite strong directional or truncating selection, may reflect
      the integration of multiple episodes of selection that occur in N. cinerea. There
      were few significant phenotypic correlations, but all the genetic correlations
      among ejaculate characters were significantly different from zero. The patterns
      of genetic variation and covariation suggest that there are important trade-offs
      among individual traits of the ejaculate and that evolution of ejaculate
      characteristics will not proceed unconstrained. Fully describing the genetic
      relationships among traits that perform as an integrated unit helps us understand
      how functional relationships constrain or facilitate the evolution of the complex
      structure that is the ejaculate.

PMID- 15446430
TI  - Integrating phylogenetics and environmental niche models to explore speciation
      mechanisms in dendrobatid frogs.
AB  - We developed an approach that combines distribution data, environmental
      geographic information system layers, environmental niche models, and
      phylogenetic information to investigate speciation processes. We used Ecuadorian
      frogs of the family Dendrobatidae to illustrate our methodology. For dendrobatids
      there are several cases for which there is significant environmental divergence
      for allopatric and parapatric lineages. The consistent pattern that many related
      taxa or nodes exist in distinct environmental space reinforces Lynch and
      Duellman's hypothesis that differential selection likely played an important role
      in species differentiation of frogs in the Andes. There is also some evidence
      that the Rio Esmeraldas basin is a geographic barrier to species distributed in
      low to middle elevations on the western side of the Andes. Another useful aspect
      of this approach is that it can point to common environmental parameters that
      correlate with speciation. For dendrobatids, sister clades generally segregate
      along temperature/elevational and/or seasonality axes. The joint analysis of
      environmental and geographic data for this group of dendrobatid frogs has
      identified potentially important speciation mechanisms and specific sister
      lineages that warrant intensive study to test hypotheses generated in this
      investigation. Further, the method outlined in this paper will be increasingly
      useful as knowledge of distribution and phylogeny of tropical species increases.

PMID- 15446431
TI  - Adaptive reptile color variation and the evolution of the Mc1r gene.
AB  - The wealth of information on the genetics of pigmentation and the clear fitness
      consequences of many pigmentation phenotypes provide an opportunity to study the
      molecular basis of an ecologically important trait. The melanocortin-1 receptor
      (Mc1r) is responsible for intraspecific color variation in mammals and birds.
      Here, we study the molecular evolution of Mc1r and investigate its role in
      adaptive intraspecific color differences in reptiles. We sequenced the complete
      Mc1r locus in seven phylogenetically diverse squamate species with melanic or
      blanched forms associated with different colored substrates or thermal
      environments. We found that patterns of amino acid substitution across different
      regions of the receptor are similar to the patterns seen in mammals, suggesting
      comparable levels of constraint and probably a conserved function for Mc1r in
      mammals and reptiles. We also found high levels of silent-site heterozygosity in
      all species, consistent with a high mutation rate or large long-term effective
      population size. Mc1r polymorphisms were strongly associated with color
      differences in Holbrookia maculata and Aspidoscelis inornata. In A. inornata,
      several observations suggest that Mc1r mutations may contribute to differences in
      color: (1) a strong association is observed between one Mc1r amino acid
      substitution and dorsal color; (2) no significant population structure was
      detected among individuals from these populations at the mitochondrial ND4 gene;
      (3) the distribution of allele frequencies at Mc1r deviates from neutral
      expectations; and (4) patterns of linkage disequilibrium at Mc1r are consistent
      with recent selection. This study provides comparative data on a nuclear gene in
      reptiles and highlights the utility of a candidate-gene approach for
      understanding the evolution of genes involved in vertebrate adaptation.

PMID- 15446432
TI  - Does viviparity evolve in cold climate reptiles because pregnant females maintain
      stable (not high) body temperatures?
AB  - Viviparity (live bearing) has evolved from egg laying (oviparity) in many
      lineages of lizards and snakes, apparently in response to occupancy of cold
      climates. Explanations for this pattern have focused on the idea that
      behaviorally thermoregulating (sun-basking) pregnant female reptiles can maintain
      higher incubation temperatures for their embryos than would be available in nests
      under the soil surface. This is certainly true at very high elevations, where
      only viviparous species occur. However, comparisons of nest and lizard
      temperatures at sites close to the upper elevational limit for oviparous reptiles
      (presumably, the selective environment where the transition from oviparity to
      viviparity actually occurs) suggest that reproductive mode has less effect on
      mean incubation temperatures than on the diel distribution of those temperatures.
      Nests of the oviparous scincid lizard Bassiana duperreyi showed smooth diel
      cycles of heating and cooling. In contrast, body temperatures of the viviparous
      scincid Eulamprus heatwolei rose abruptly in the morning, were high and stable
      during daylight hours, and fell abruptly at night. Laboratory incubation
      experiments mimicking these patterns showed that developmental rates of eggs and
      phenotypic traits of hatchling B. duperreyi were sensitive to this type of
      thermal variance as well as to mean temperature. Hence, diel distributions as
      well as mean incubation temperatures may have played an important role in the
      selective forces for viviparity. More generally, variances as well as mean values
      of abiotic factors may constitute significant selective forces on life-history
      evolution.

PMID- 15446434
TI  - Altruism via kin-selection strategies that rely on arbitrary tags with which they
      coevolve.
AB  - Hamilton's rule explains when natural selection will favor altruism between
      conspecifics, given their degree of relatedness. In practice, indicators of
      relatedness (such as scent) coevolve with strategies based on these indicators, a
      fact not included in previous theories of kin recognition. Using a combination of
      simulation modeling and mathematical extension of Hamilton's rule, we demonstrate
      how altruism can emerge and be sustained in a coevolutionary setting where
      relatedness depends on an individual's social environment and varies from one
      locus to another. The results support a very general expectation of widespread,
      and not necessarily weak, conditional altruism in nature.

PMID- 15446433
TI  - Historical diversification of migration patterns in a passerine bird.
AB  - Migratory strategies of birds require complex orientation mechanisms,
      morphological adaptations, and life-history adjustments. From an evolutionary
      perspective, it is important to know how fast this complex combination of traits
      can evolve. We analyzed mitochondrial control-region DNA sequences in 241
      blackcaps (Sylvia atricapilla) from 12 populations with different migratory
      behaviors. The sample included sedentary populations in Europe and Atlantic
      archipelagos and migratory populations with different distances of migration,
      from regional to intercontinental migrations, and different heading directions
      (due to a migratory divide in central Europe). There was no genetic structure
      between migratory and sedentary populations, or among populations from different
      biogeographic areas (Atlantic islands, the Iberian Peninsula, or the continent),
      however we found evidence of a genetic structure when comparing populations
      located on either side of the migratory divide. These findings support an
      independent evolution of highly divergent migratory strategies in blackcaps,
      occurring after a postglacial colonization of the continent along western and
      eastern routes. Accordingly, mismatch-distribution analyses suggested an
      expansion of blackcaps from a very small population size, and time estimates
      dated such an expansion during the last postglacial period. However, the
      populations in Gibraltar, located in a putative Mediterranean refuge, appeared to
      be independent of these processes, showing evidence of restricted gene flow with
      other populations and demonstrating insignificant historical changes in effective
      population size. Our results show that the interruption of gene flow between
      migratory and sedentary populations is not necessary for the maintenance of such
      a polymorphism, and that even the most divergent migratory strategies of a bird
      species are susceptible to evolution in response to historical environmental
      changes.

PMID- 15446435
TI  - A likelihood-based approach to estimating and testing for isolation by distance.
AB  - Simple regression of genetic similarities between pairs of populations on their
      corresponding geographic distances is frequently used to detect the presence of
      isolation by distance (IBD). However, these pairwise values are obviously not
      independent and there is no parametric procedure for estimating and testing for
      the IBD intercepts and slopes based on standard regression theory. Nonparametric
      tests, such as the Mantel test, and resampling techniques, such as bootstrapping,
      have been exploited with limited success. Here, I describe a likelihood-based
      analysis to allow for simultaneously detecting patterns of correlated residuals
      and estimating and testing for the presence of IBD. It is shown, through the
      analysis of two molecular datasets in pine species, that different covariance
      structures of the residuals exist. More over, the likelihood ratio tests under
      these covariance structures are less sensitive to the presence of IBD than the
      Mantel test and the simple regression analysis but more sensitive than the
      bootstrap and jackknife samples over independent populations or population pairs.
      Because the likelihood analysis directly models and accounts for nonindependence
      of residuals, it should legitimately detect the presence of IBD, thereby allowing
      for accurate inferences about evolutionary and demographic processes influencing
      the extent and patterns of IBD.

PMID- 15446436
TI  - Mechanisms of sperm competition: testing the fair raffle.
AB  - Sperm competition is a major force of sexual selection, but its implications for
      mating system and life-history evolution are just beginning to be understood. Of
      particular importance is understanding the mechanisms of sperm competition.
      Models have been developed to determine if sperm competition operates in a fair
      raffle process, whereby each sperm from competing males has an equal chance of
      fertilizing a female's ova, or if it operates in a loaded raffle process, whereby
      one male's sperm has a fertilization advantage. These models require data on
      relative sperm and offspring (paternity) numbers of competing males. Here we
      develop a model based on maximum-likelihood methods for differentiating between
      the fair and loaded raffle processes. The model calculates the relative
      competitiveness of two males' sperm (loadings) as well as the economy of scale
      (nonlinear returns to sperm number). Previous models implicitly assumed that
      there is no economy of scale, which may not be the case when there is cooperation
      or interference among sperm from a given male. We demonstrate that our model has
      superior power-in some instances more than double-than previous models. We apply
      our model to an example of sperm competition in the guppy (Poecilia reticulata)
      and show that the system may be characterized by a loaded raffle attributable to
      effects of second male precedence.

PMID- 15446437
TI  - A test for patterns of modularity in sequences of developmental events.
AB  - This study presents a statistical test for modularity in the context of relative
      timing of developmental events. The test assesses whether sets of developmental
      events show special phylogenetic conservation of rank order. The test statistic
      is the correlation coefficient of developmental ranks of the N events of the
      hypothesized module across taxa. The null distribution is obtained by taking
      correlation coefficients for randomly sampled sets of N events. This test was
      applied to two datasets, including one where phylogenetic information was taken
      into account. The events of limb development in two frog species were found to
      behave as a module.

PMID- 15446438
TI  - A test of the chromosomal rearrangement model of speciation in Drosophila
      pseudoobscura.
AB  - Recent studies suggest that chromosomal rearrangements play a significant role in
      speciation by preventing recombination and maintaining species persistence
      despite interspecies gene flow. Factors conferring adaptation or reproductive
      isolation are maintained in rearranged regions in the face of hybridization,
      while such factors are eliminated from collinear regions. As a direct test of
      this rearrangement model, we evaluated the genetic basis of hybrid male sterility
      in a sympatric species pair, Drosophila pseudoobscura pseudoobscura and D.
      persimilis, and an allopatric species pair, D. pseudoobscura bogotana and D.
      persimilis. Our results are consistent with the proposed model: virtually all of
      the sterility factors in the former pair are associated with three inverted
      regions, whereas sterility factors are present in the collinear regions in the
      latter pair. These findings indicate recombination and selection may have
      eliminated sterility factors outside the inverted regions between D. p.
      pseudoobscura and D. persimilis, suggesting chromosomal rearrangements may
      facilitate species persistence despite hybridization.

PMID- 15446439
TI  - Opposing selection on a sexually dimorphic trait through female choice and male
      competition in a water boatman.
AB  - Female choice and male-male competition are traditionally considered to act in
      concert, with male competition facilitating female choice. This situation would
      enforce the strength of directional selection, which could reduce genetic
      variation and thus the benefits of choice. Here I show that in a water boatman,
      Sigara falleni, the direction of selection through female choice and male
      competition vary among traits under laboratory conditions. The two forces were
      mutually enforcive in acting on body size but exerted opposing selection on a
      sexually selected trait, male foreleg pala size. Female choice favored large
      palae, whereas male competition favored smaller palae, suggesting that large
      palae are costly in competition. This conflicting selection through female choice
      and male competition could be one of the forces that contribute to the
      maintenance of genetic variation in sexually selected traits.

PMID- 15446440
TI  - Rates of evolution of hybrid inviability in birds and mammals.
AB  - Almost 30 years ago, A. C. Wilson and colleagues presented results indicating
      that hybrid inviability between species evolves 10 times faster in mammals than
      in birds and frogs. Here I revisit this question for birds and mammals using
      modern molecular data (mitochondrial cytochrome b DNA) and a more
      phylogenetically appropriate statistical approach. My analyses confirm that
      diverging mammals lose the ability to form viable hybrids faster than birds. To
      explain the difference in rates of evolutionary loss of hybridization potential,
      Wilson and coworkers proposed that mammals have higher rates of regulatory
      evolution, causing higher probabilities of developmental incompatibilities
      between mammal species. I briefly discuss this and other potential explanations.

PMID- 15446441
TI  - Calibration of molecular clocks and the biogeographic history of Crypteroniaceae.
AB  - A recent molecular clock analysis concluded that Gondwanan vicariance and out-of
      India dispersal best explained the distribution of Crypteroniaceae and its allies
      (Conti et al. 2002). A reanalysis of their data using a different molecular
      dating technique and calibration point is congruent with an alternative
      hypothesis, namely dispersal between India, Africa, and South America long after
      the initial break-up of Gondwana.

PMID- 15446442
TI  - Structural and physiological aspects of cell death.

PMID- 15446443
TI  - The role of apoptosis in non-mammalian host-parasite relationships.
AB  - It is clear that the roles of apoptosis in the interactions between the parasite
      and their non-mammalian hosts are multifaceted and highly dependent on individual
      associations between the two organisms involved. Whilst there are instances where
      both organisms appear to gain from the apoptotic mechanism induced, in the
      majority of cases apoptosis appears to favour only one of the parties. In the
      instances when the parasite benefits, the apoptosis has been related to
      infectivity and virulence, an interruption of the killing mechanism of the host,
      and liberation of the pathogen. However, there are occasions where the apoptotic
      process benefits the host, as controlled cell death has been associated with
      limiting the pathogen population, parasite migration within the host and, in some
      instances, actually killing the invading organism. Apoptosis thus appears to play
      several fundamental roles within the host-parasite relationship which is
      ultimately reflected in an effect on the host population either mediated through
      an alteration in host fecundity or reduction in host numbers. The next decade
      promises to be both exciting and productive with respect to our knowledge of the
      relationship between apoptosis in non-mammalian animals and infection. Over the
      last few years the information obtained from studies on the apoptotic process in
      mammals and invertebrates (i.e. C. elegans and Drosophila) have been effectively
      used to increase our understanding of the apoptotic process in other animals such
      as insects, fish and amphibians. Such knowledge has paved the way for extensive
      studies on the effect of infections to be carried out.

PMID- 15446444
TI  - Thionine-positive cells in relation to parasites.

PMID- 15446445
TI  - Animal models for the study of innate immunity: protozoan infections in fish.

PMID- 15446446
TI  - The pathophysiology of salmonid cryptobiosis and Glossina-transmitted mammalian
      trypanosomiasis in livestock.

PMID- 15446447
TI  - The biology of parasites from the genus Argulus and a review of the interactions
      with its host.

PMID- 15446448
TI  - Interactions between sea lice and their hosts.

PMID- 15446449
TI  - Interactive associations between fish hosts and monogeneans.

PMID- 15446450
TI  - Comparative aspects of the tick-host relationship: immunobiology, genomics and
      proteomics.

PMID- 15446451
TI  - Avian coccidiosis: a disturbed host-parasite relationship to be restored.
AB  - The co-evolution of Eimeria and its host the domestic chicken has resulted in a
      delicate balance of mutual understanding and respect. This balance has been
      broken by the complete change of the environment in which the parasite was able
      to reproduce to such an extent that the host, stressed and weakened by heat,
      crowding and concurrent infections could not combat the shear numbers of
      organisms. The use of drugs to control the situation has been shown to only
      temporarily create relief. Resistance widely developed by the flexible genome of
      the parasite returned new drugs at a greater speed than they had been developed.
      Improved hygienic measures, better facility management and good understanding of
      epidemiology of the parasites spreading and proliferation seem the first and most
      promising set of tools to control the balance. Reduction of stock density may
      only provide any relief if this is done at a factor of 10 or higher and this is
      not a realistic measure in relation to the profit. Free-range chickens are an
      alternative if only animal welfare is at stake. However, in terms of prevalence
      of parasitic infections, such as coccidia, helminthes or ectoparasites, chickens
      do not seem to be better off (Permin et al., 2002). Immunological surveillance
      and the development of safe, effective and economical vaccines are further
      refinements that can be used to restore the relationship between parasite and
      host. Several live vaccines are effective and applied, but certainly have
      drawbacks in safety and production. New technology such as recombinant vectors
      together with a better understanding of the cell biology of the parasite from
      biological and genomic information should provide improved vaccines for the
      future. The strong genetically determined characteristics involved in the
      induction and maintenance of a sustainable protective immune response might turn
      out to be of decisive importance for the success of these strategies. The
      consequences for the physiology of the parasite remain to be understood.

PMID- 15446452
TI  - [Endocrine diseases and diabetes].
AB  - Disorders of endocrine system are often associated with diabetes mellitus.
      Overproduction of hormones with hyperglycaemic effect, for example that of growth
      hormone or cortisol, can lead to impaired glucose tolerance or even to induce
      manifestation of diabetes mellitus. Autoimmune character of some endocrinopathies
      is a well-known cause of diabetes mellitus type 1 and also of the thyroid gland
      involvement. Diabetes mellitus, especially with a poor glycaemic control,
      influences various functions of endocrine organs. The most frequent disturbances
      are the slow down of the growth in children and adolescents and hypothalamo
      pituitary-gonadal axis dysfunction in women. This review summarizes relationship
      between the most common endocrinopathies and diabetes mellitus.

PMID- 15446453
TI  - [Suprasegmental effects of selective posterior rhizotomy].
AB  - The occurrence of spasticity is most commonly attributed to the lack of
      presynaptic inhibition. Perinatal damage to the central nervous system, as it
      happens in cerebral palsy, leads to pathological reflex response both on
      segmental and polysegmental levels. It results not only in clinical signs typical
      for spasticity but also in alterations of brainstem function, such as dysarthria
      or congenital nystagmus. Selective posterior rhizotomy is a neurosurgical method,
      routinely used in the treatment of spasticity. The lumbosacral posterior roots
      are partially cut under perioperative neurophysiological control. The aim of the
      treatment is the reduction of afferentation for posterior horns resulting in a
      decrease of pathological reflex responses. Selective posterior rhizotomy
      consequently decreases lower limbs spasticity. The improvement of upper
      extremities fine skills, the improvement of speech and cognitive functions has
      been also observed after selective posterior rhizotomy. The possible
      pathophysiological explanations of these so-called suprasegmental effects are
      discussed in the article.

PMID- 15446454
TI  - [Hereditary disorders of mitochondrial ATP synthase].
AB  - Primary disorders of mitochondrial ATP synthase belong to the most severe
      mitochondrial diseases. They can be caused by heteroplasmic mtDNA mutations in
      ATP6 gene that affect ability of enzyme to synthesise ATP, or by mutations in
      nuclear genes encoding factors essential for biosynthesis and assembly of the
      catalytic F1-part of the enzyme. In the latter case the cellular content of the
      enzyme decreases to < or = 30%. In both types of defects low production of ATP
      appears to be associated with increased mitochondrial ROS production related to
      elevated levels of mitochondrial membrane potential.

PMID- 15446455
TI  - [Specific complications in the treatment with implantable cardioverter
      defibrillators].
AB  - BACKGROUND: Using implantable cardioverter-defibrillators in treatment of
      malignant ventricular arrhythmias revealed new complications specific to this
      therapy. Inappropriate therapy, arrhythmic storm and device related proarrhythmia
      belong to the most significant complications. The authors describe specific
      complications in a group of ICD patients, analyze their etiology and prognostic
      value. There are some recommendations for the management of specific
      complications. METHODS AND RESULTS: 138 consecutive patients underwent ICD
      implantation between 1994-2001. Median follow-up was 47,35 months. Average left
      ventricular ejection fraction was 38 +/- 14% and 71% of patients suffered from
      coronary artery disease. From the total of 2490 arrhythmic episodes 1490 were
      evaluated in detail. 253 episodes (17%) were classified as inappropriate therapy.
      The most common etiology of inappropriate therapy was atrial fibrillation with
      rapid ventricular response (68%), atrial flutter (13%) and sinus tachycardia
      (11%). After the therapeutic intervention, 65% of them remained free of
      inappropriate therapy. There were 38 arrhythmic storms in 19 patients as another
      serious complication. CONCLUSIONS: All the observed arrhythmic episodes were
      ventricular tachycardias (p<0.04). Patients with arrhythmic storm in history had
      significantly lower survival (p<0.05). The risk factors of cardiac nonsudden
      death were: age >66 years, left ventricular ejection fraction <35% and arrhythmic
      storm history. The authors present recommendations for the treatment of the most
      common specific ICD complications.

PMID- 15446457
TI  - [The use of bioimpedance analysis for the assessment of relative body fat in
      obese women].
AB  - BACKGROUND: Bioimpedance analysis (BIA) is often used for the assessment of
      relative body fat (%BF). The accuracy of the test depends on prediction equation
      used, which respects the group of population, body composition, age and gender of
      the individual. The requirement to construct a specific prediction equation for
      obese population with more than 30% body fat was suggested. The objective of the
      study was to evaluate the validity of bioimpedance analysis and to develop
      population-specific prediction equation for obese women. METHODS AND RESULTS:
      Relative body fat were measured in set of 63 obese women by means of 3 methods:
      tetrapolar bioimpedance analysis, bipedal bioimpedance analysis and dual energy X
      ray absorbtiometry (DEXA). Significant differences were found among mean values
      of %BF measured by methods above (39.9%, 42.2% and 48.7%, respectively).
      Significant correlation between results obtained by tetrapolar BIA and by DEXA
      method was noticed (R=0.73). New specific prediction equation was developed for
      measuring %BF of obese women by tetrapolar BIA. No good agreement between bipedal
      BIA and DEXA method was found. CONCLUSIONS: By using the new prediction equation,
      measurement of the relative body fat in obese women by tetrapolar bioimpedance
      analysis was comparable with the reference DEXA method.

PMID- 15446458
TI  - [The contribution of 24-hour ambulatory blood pressure monitoring to the
      treatment of hypertensive patients in teaching hospital in Nitra].
AB  - BACKGROUND: Twenty-four hours ambulatory blood pressure monitoring (ABPM) in
      patients with arterial hypertension is a recognized method for diagnostic of
      hypertension and for monitoring of the effects of antihypertensive treatment. The
      aim of our study was to evaluate the contribution of ABPM in clinical practise.
      METHODS AND RESULTS: Records of ABPM in hypertensive patients were evaluated
      retrospectively. Total of 37 patients aged 27-69 years with the newly diagnosed
      hypertension in the period of 1996-2001 were included in the study. The
      indications to ABPM, percent of dippers and no dippers diagnosed on the basis of
      diurnal index and the modification in antihypertensive treatment in no dippers
      were analysed. 1) ABPM was used for monitoring of the effect of antihypertensive
      therapy in 78%, for diagnosing borderline hypertension in 19% and of white coat
      hypertension in 3% cases; 2) 22 patients (59%) were diagnosed as no dippers; 3)
      Antihypertensive therapy was modified in 7 patients no dippers (20%).
      CONCLUSIONS: The contribution of ABPM is obvious, however at current conditions
      its broader application could increase the diagnostic and therapeutical quality
      of clinical decision making in hypertensive patients.

PMID- 15446459
TI  - [Nijmegen breakage syndrome in Slovakia].
AB  - BACKGROUND: The autosomal recessive Nijmegen breakage syndrome (NBS) is a DNA
      repair disorder due to a mutation in the NBS1 gene on 8q21. Hyperradiosensitivity
      and high risk for lymphoreticular malignancy are important reasons for early
      diagnosis and prevention by avoidance of ionisation. The frequency of NBS
      heterozygotes of the mutation 657de15, which is predominant in the Slavic
      population was estimated to be in the range of 1:90-1:314 in different parts of
      Poland, and 1:128-154 among Czech newborns, born 20 years ago. METHODS AND
      RESULTS: Lower prevalence of affected homozygotes born in Czechoslovakia in the
      period 1969- 1992 (24 among 5.2 million newborns corresponds to 1:271000) than
      expected on the basis of carrier frequency is explained to be due to
      underdiagnosing because the rate of prenatal lethality in the NBS families is not
      increased or it is even lower than in the general population. The underdiagnosing
      of NBS is emphasized also by the mean age at diagnosis (7.5 years) although
      severe microcephaly is present at birth. The possibility to offer effective
      prevention of primary and secondary malignancies becomes the motivation for
      interdisciplinary collaboration with paediatricians, neurologists, immunologists
      and clinical geneticists. A decrease of the mean age down to 6 months at
      diagnosis among the 11 newly recognized patients has been achieved in the
      previous 4 years. The occurrence of homozygotes was relatively higher in Slovakia
      with 5 million inhabitants (14 patients in 11 families) than in the Czech
      Republic with a population of 10 million (21 patients in 14 families), and
      therefore the frequency of NBS heterozygotes was studied among 2996 newborns born
      in 2002-2003 in 12 maternity hospitals of west, middle and east Slovakia.
      Surprisingly, only 3 heterozygotes were found. CONCLUSIONS: This discrepancy of
      heterozygote frequency and the number of homozygotes shows that due to
      traditional subisolates the population is not in the genetic equilibrium. It
      explains the high prevalence of alcaptonuria in Slovakia in the middle of last
      century, which is a rare disorder in other countries.

PMID- 15446460
TI  - [Increased sensitivity for detection of mutations in exon 15 of the APC gene in
      patients with familial adenomatous polyposis].
AB  - BACKGROUND: Protein Truncation Test (PTT) was used to detect mutations in exon 15
      of the APC gene in patients with Familial Adenomatous Polyposis. This method is
      limited by its ability to detect polypetide chains up to a certain minimum
      length. The aim of this study was to increase the sensitivity of detection of
      mutations in this region by using the technique of Denaturing Gradient Gel
      Electrophoresis (DGGE). METHODS AND RESULTS: Study were performed on 122 patients
      without detected mutations in the APC gene. The patients were divided into two
      independent groups 15A and 15A+15B (with 51 and 71 patients respectively). All
      the patients were tested with the DGGE and the positive findings were confirmed
      with sequencing. No mutation was detected in the group 15A (0%). In group 15A+15B
      one (1.4%) polymorphism and four (5.63%) patients with nonsense mutations were
      detected. CONCLUSIONS: DGGE is an effective method for detecting mutations in the
      first part of exon 15 of APC gene. It allows detecting any change in DNA strand.
      DGGE complements PTT in scanning of the whole exon 15 of APC gene.

PMID- 15446461
TI  - [Polypharmacotherapy in clinical gerontology].
AB  - Multimorbidity frequently develops in old age and it is usually accompanied with
      pharmacotherapy of elderly patients. The growing number of seniors and
      comparatively low attention given to this reality among the medical community
      makes the problem highly significant for the practical medicine. Solution
      requires in the broad medical community a deeper knowledge of
      gerontopharmacotherapy and of its specific features, including the
      pharmacodynamics and pharmacokinetics in elderly organism. Non-geriatric
      physicians will face in their daily clinical praxis the questions of drug
      interactions and undesirable general and local side effects. Moreover, some
      foods, beverages or preservatives can influence the pharmacological effect. Due
      to multimorbidity in the senescence, such problems can be linked to large
      geriatric syndromes (instability with downfalls, immobility, decubitus,
      incontinency, intellectual and sensory defects of vision and hearing).

PMID- 15446462
TI  - [Hypoplasia of trachea with tracheal bronchus as a complication of surgical
      correction of tetralogy of Fallot].
AB  - A 10 months old infant underwent repair of tetralogy of Fallot with hypoplastic
      annulus of the pulmonary valve, diminutive pulmonary arteries, right aortic arch
      and left superior vena cava. The right ventricular outflow tract was
      reconstructed using a monocusp patch. The postoperative course was unfavourably
      influenced by respiratory complications due to tracheal bronchus and hypoplasia
      of trachea, which were not diagnosed preoperatively. Extreme emphysema of the
      right upper and middle lobes compromised haemodynamics. Repeated reoperations
      were required. The upper and the middle lobes of the right lung had to be
      resected, the hypoplastic trachea reconstructed with a pericardial patch and
      pulmonary homograft inserted. One year later, homograft had to be replaced and
      tricuspid annuloplasty performed for pulmonary and tricuspid regurgitation and
      right ventricular dilatation as a consequence of increased pulmonary artery
      pressure. Three years after the original surgery the patient remains in good
      clinical condition.

PMID- 15446463
TI  - Non-compliance--some myths, some facts.
AB  - Patient non-compliance is a common problem, well known to every practitioner. It
      is widespread among all patients, regardless of the disease type and intensity.
      The consequences of non-compliance are very serious, and include inefficacy of
      applied treatment, deterioration of patient's health state, necessity of
      additional tests and hospitalisation or even death. Non-compliance also generates
      increased expenditure within the health care system. Despite all these serious
      consequences, in many cases doctors do not fully realise how frequently it
      occurs. Fortunately, there are ways to achieve better compliance. Their
      implementation may contribute to achieving better results of the therapy and
      reducing health system expanses at the same time.

PMID- 15446464
TI  - [Alcohol and other addictive drugs in children. Prevention in the family].
AB  - Serious effects of the alcohol and other drug abusus on the brain of young people
      were repeatedly proved. During puberty and adolescence, somatic and mental
      changes develop, and new neuronal networks are formed. Even a modest memory and
      learning impairment by alcohol or drugs brings about worse results in the study
      and later on in the occupation.

PMID- 15446465
TI  - [Clinical epidemiology--the risk of impairment].
AB  - Basic principles of the critical assessment of harm risk studies are described in
      this paper. Assessment of validity, importance and applicability of such studies
      is presented in details and possible problems, complicating proper interpretation
      of results are pointed out.

PMID- 15446466
TI  - [Alphabet of stopping smoking--why people smoke?].
AB  - This paper describes the principle of tobacco dependence--psychosocial and
      physical (drug) dependence, reasons for starting, maintaining or stopping
      smoking, including treatment barriers. It deals with individual needs of nicotine
      doses and socio-economic relations.

PMID- 15446467
TI  - Genetic analysis of litter size, parturition length, and birth assistance
      requirements in primiparous sows using a joint linear-threshold animal model.
AB  - The aim of this study was to investigate whether selection for number of live
      born piglets has led to prolonged parturition and increased requirement for birth
      assistance, resulting in increased numbers of stillborn piglets. Data were
      collected from 6,718 primiparous Norwegian Landrace sows farrowing between 2001
      and 2003. The need for birth assistance was recorded as a binary response.
      Physical intervention in the birth of piglets and/or hormonal treatment by the
      farmer was recorded as birth assistance. The duration of the parturition was
      analyzed as a binary trait (<4 h and >4 h). The statistical model used for
      analysis included contemporary groups of herd-year, litter breed, season of
      farrowing, parity in which the sow was born, a regression on the age of sow at
      farrowing, an additive genetic effect, and a service sire effect. A full Bayesian
      approach via Gibbs sampling was adopted to estimate the genetic relationships
      between these four traits. A total chain length of 100,000 iterations was run.
      The first 10,000 samples were discarded as burn-in, and the remaining 90,000
      iterations were retained without thinning for post-Gibbs analysis. The highest
      direct heritability was estimated for the number of live-born piglets (h2 =
      0.07), followed by the duration of farrowing (h2 = 0.05), the need for birth
      assistance (h2 = 0.05), and the number of stillborn piglets (h2 = 0.04). The
      genetic correlations revealed that the number of live and stillborn piglets was
      uncorrelated; however, the number of live piglets born had a moderate genetic
      correlation to the need for birth assistance (rg = 0.24 +/- 0.01) and duration of
      farrowing (rg = -0.20 +/- 0.01), whereas the number of stillborn piglets was
      highly correlated to the need for birth assistance (rg = 0.74 +/- 0.01) and the
      duration of parturition (rg = 0.66 +/- 0.01). The duration of farrowing and the
      need for birth assistance were genetically highly correlated (rg = 0.89 +/-
      0.00). For all traits, the service sire variance was approximately one quarter in
      magnitude compared with its respective genetic variance. The results showed that
      selection for the number of live born piglets is not expected to influence the
      number of stillborn piglets. Increasing the number of live piglets born through
      selection should have a slight negative effect on farrowing duration and a minor
      increase in the need for birth assistance. Sows with a high genetic potential for
      birth assistance and prolonged parturition were more likely to give birth to
      greater numbers of stillborn piglets.

PMID- 15446468
TI  - Growth and compositional changes of fetal tissues in pigs.
AB  - Three hundred twenty fetuses were obtained from 33 pregnant gilts (Camborough-22,
      Pig Improvement Co.) to determine rates of nutrient deposition in fetal tissues
      and to estimate nutrient requirements for fetal growth. Pregnant gilts were fed
      an equal amount of a gestation diet (2.0 kg/d; as-fed basis), and were
      slaughtered at d 0, 45, 60, 75, 90, 102, or 110 of gestation (n = 3 to 6 per
      day). Fetuses were dissected into carcass and individual tissues (including
      gastrointestinal tract, liver, lung, heart, kidney, spleen [> or = d 75]), and
      partial placental collection was made for chemical analysis. Fetal tissues were
      weighed and analyzed for DM, ash, CP, and crude fat. Regression equations were
      obtained to explain the weight and compositional changes of individual tissues
      during gestation. Weights of the fetus, carcass, gastrointestinal tract, liver,
      heart, lung, and kidney increased cubically (P < 0.001), whereas brain weight
      increased linearly (P < 0.001) as gestation progressed. Fetal protein and fat
      contents increased quadratically (P < 0.001) as gestation progressed (R2 = 0.906
      and 0.904, respectively). Changes in fetal protein and fat contents fit a
      multiphasic regression that consisted of two linear equations (P < 0.001, R2 =
      0.988 and P < 0.001, R2 = 0.983, respectively), indicating that protein and fat
      growth accelerated after d 69 of gestation. Fetal protein and fat accretions were
      0.25 and 0.06 g/d (P < 0.001) before d 69 of gestation, and increased to 4.63 and
      1.09 g/d (P < 0.001) after d 69 of gestation. Protein needs for tissue protein
      gains increased 19-fold after d 69 of gestation. Results of this study indicate
      that the growth of the fetus and fetal tissues occurs at different rates during
      gestation and support the practice of a two-phase feeding strategy (before and
      after approximately d 70 of gestation) for pregnant gilts.

PMID- 15446469
TI  - Effect of nutrient restriction on calpain and calpastatin content of skeletal
      muscle from cows and fetuses.
AB  - Calpains are crucial for the degradation of myofibrillar proteins in muscle.
      Calpastatin is a specific inhibitor of calpains. The objective of this study was
      to elucidate the effect of nutrient restriction on the activity of calpains and
      calpastatin in the skeletal muscle of both cows and fetuses. Beginning 30 d after
      conception, 20 cows were fed either a control diet consisting of native grass hay
      fortified with vitamins and minerals at recommendations for a mature cow to gain
      0.72 kg/d or half the vitamins and minerals and millet straw at 68.1% of NEm
      requirements. Cows were slaughtered on d 125 of gestation, and the LM was sampled
      at the 12th rib for calpain and calpastatin measurement. When comparing the
      muscle samples from nutrient-restricted and control cows, no difference in the
      activity of calpain I and II was observed; however, there was a significant
      difference (P < 0.05) in calpastatin activity. Muscle samples from control cows
      had greater calpastatin content than those of nutrient-restricted cows (P <
      0.05); in contrast, the calpastatin content of fetal muscle was greater in
      fetuses gestated by nutrient-restricted cows than those of control cows (P <
      0.05). Further, there were three calpastatin isoforms of 125, 110, and 70 kD
      detected in fetal muscle, whereas only the110-kD isoform was detected for cow
      muscle. These results indicate that the activity of the calpain system in
      skeletal muscle is mainly controlled through the expression of calpastatin.
      Alternating the calpastatin content in muscle and thereby modulating calpain
      activity may provide a mechanism for the maintenance of fetal muscle growth
      during nutrient restriction, whereas skeletal muscle loss in cows is upregulated.

PMID- 15446470
TI  - Effects of feed restriction on reproductive and metabolic hormones in ewes.
AB  - The goal of this study was to determine the effects of short-term feed withdrawal
      on reproductive and metabolic hormones during the luteal phase of the estrous
      cycle in mature ewes. Mature ewes observed in estrus were assigned randomly to
      control and fasted groups (n = 10 per group Trials 1 and 2). For Trials 1 and 2,
      control ewes had ad libitum access to feed, whereas fasted ewes were not fed from
      d 7 through 11 of their estrous cycle; on d 12, all ewes were treated with 10 mg
      of PGF2alpha, and fasted ewes were gvien ad libitum access to feed. For Trial 1,
      blood samples were collected daily through fasting and at 2-h intervals following
      PGF2alpha for 72 h. Serum concentrations of insulin (P < or = 0.002) and IGF-I (P
      < or = 0.01), but not GH (P > or = 0.60), were decreased during fasting compared
      with fed ewes. Serum concentrations of 29 (P = 0.02) and 34 kDa (P = 0.04) IGFBP
      were greater in fasted ewes at 96 h after initiation of fasting than in control
      ewes. Two control and four fasted ewes in Trial 1 did not exhibit a preovulatory
      surge release of LH by 72 h. Therefore, Trial 2 was conducted so that the timing
      of the LH surge could be predicted following the collection of blood samples at 2
      h intervals for 112 h and then at 6-h intervals until 178 h following PGF2alpha
      administration and realimentation. The magnitude of the preovulatory LH surge in
      Trial 2 was decreased (P = 0.009) and delayed (P = 0.04), and serum
      concentrations of estradiol were diminished (P < or = 0.03) 12 h before the LH
      surge in fasted ewes. Ovulation rates were not influenced (P > or = 0.32) by
      fasting in Trials 1 and 2. Serum concentrations of progesterone in both Trials 1
      and 2 were, however, greater (P < 0.001) in fasted than in control ewes. A third
      trial with ovariectomized ewes was conducted to determine whether the increased
      serum concentrations of progesterone observed in fasted ewes during Trials 1 and
      2 were ovarian-derived. Ovariectomized ewes were implanted with progesterone
      containing intravaginal implants and allotted to control (n = 5) or fasted (n =
      5) treatment groups and fed as described for Trials 1 and 2. Similar to intact
      ewes, serum concentrations of progesterone were approximately twofold greater (P
      < 0.001) in fasted than in control implanted ovariectomized ewes. In summary,
      feed withdrawal for 5 d during the luteal phase of the estrous cycle increased
      serum concentrations of progesterone and evoked endocrine changes that could
      perturb the subsequent estrous cycle.

PMID- 15446471
TI  - Inhibition of endogenous nitric oxide production influences ovine hindlimb
      metabolism independently of insulin concentrations.
AB  - The hindlimb arteriovenous difference (AVD) model was used to determine whether
      30 mg/ kg of the nitric oxide synthase (NOS) inhibitor L-NGnitroarginine methyl
      ester (hydrochloride; L-NAME) inhibited ovine NO synthesis and influenced muscle
      metabolism. Eight Border Leicester x Merino cross lambs (50 to 55 kg BW) were
      infused with saline (control) or saline containing L-NAME via an indwelling
      jugular vein catheter in a balanced randomized crossover design with 3 d between
      treatments. The abdominal aorta and deep femoral vein were catheterized for
      assessment of AVD of hind limb metabolism. Arterial hematocrit and insulin
      concentration and both arterial and venous concentrations of nitrate/nitrite
      (NOx), glucose, lactate, NEFA, and urea were determined. Infusion of L-NAME
      decreased arterial NOx concentrations (P = 0.049), indicating inhibition of
      systemic NO synthesis. Treatment had no effect on arterial (3.5 vs. 3.6 +/- 0.19
      mmol/L for control and L-NAME lambs, respectively; P = 0.39) or venous (3.3 vs.
      3.4 +/- 0.16 mmol/L, P = 0.55) plasma glucose concentrations or on glucose AVD
      (0.19 vs. 0.27 +/- 0.065 mmol/L, P = 0.20). There was an interaction (P = 0.038)
      between time and treatment, such that L-NAME initially increased the AVD of
      glucose (up to 180 m) divergent from control lambs. The response was then
      decreased before a possible inflection beyond 240 min. Infusion of L-NAME
      increased hindlimb venous NEFA (222 vs. 272 +/- 13.2 micromol/L, P = 0.007) and
      NEFA AVD (79.4 vs. -13.3 +/- 31.5 micromol/L, P = 0.018). These metabolic changes
      were independent of plasma insulin concentrations, which were not affected by L
      NAME infusion (25.3 vs. 27.8 +/- 3.62 mU/L, P = 0.85). The increase in hindlimb
      lipolysis after L-NAME infusion does not seem to be due to increased lipolysis of
      plasma triacylglycerol because circulating arterial (155 vs. 142 +/- 20.8
      micromol/L, P = 0.58), venous (154 vs. 140 +/- 20.5 micromol/L, P = 0.50), and
      AVD (1.0 vs. 2.9 +/- 3.17 micromol/L, P = 0.38) triacylglycerol concentrations
      were unaffected by L-NAME infusion. In conclusion, these data indicate that
      infusion of 30 mg of L-NAME/kg inhibits NO synthesis, which in turn influences
      fat and carbohydrate metabolism in the ovine hindlimb independently of plasma
      insulin concentrations.

PMID- 15446472
TI  - Assessment of the feeding value of South Dakota-grown field peas (Pisum sativum
      l.) for growing pigs.
AB  - Four experiments were conducted to investigate the feeding value of South Dakota
      grown field peas (Pisum sativum L.) for growing pigs. In Exp. 1, 96 pigs (initial
      BW = 22 +/- 3.35 kg) were allotted to four treatment groups (four pigs per pen,
      six replicate pens per treatment) and fed growing (0.95% Lys) and finishing
      (0.68% Lys) diets containing 0, 12, 24, or 36% field peas (as-fed basis). There
      were no differences among the treatment groups in ADG, ADFI, or G:F. Likewise,
      there were no differences in backfat thickness or lean meat percent among
      treatment groups, but pigs fed diets containing 12, 24, or 36% field peas had
      greater (P < 0.05) loin depths than pigs fed the control diet. In Exp. 2, 120
      pigs (initial BW = 7.8 +/- 1.04 kg) were allotted to four treatment groups 2 wk
      after weaning. Pigs were then fed diets containing 0, 6, 12, or 18% field peas
      (as-fed basis) during the following 4 wk. There were five pigs per pen and six
      replicate pens per treatment. Results of the experiment showed no differences in
      ADG, ADFI, or G:F among treatment groups. In Exp. 3, apparent (AID) and
      standardized (SID) ileal digestibility coefficients of CP and AA in field peas
      and soybean meal were measured using six individually penned growing pigs
      (initial BW = 36.5 +/- 2.1 kg) arranged in a repeated 3 x 3 Latin square design.
      The AID for Met, Trp, Cys, and Ser, and the SID for Met, Trp, and Cys were lower
      (P < 0.05) in field peas than in soybean meal; but for CP and all other AA, no
      differences in AID or SID were observed between the two feed ingredients.
      Experiment 4 was an energy balance experiment conducted to measure the DE and ME
      concentrations in field peas and corn. Six growing pigs (initial BW = 85.5 +/-
      6.5 kg) were placed in metabolism cages and fed diets based on field peas or corn
      and arranged in a two-period switch-back design. The DE values for field peas and
      corn (3,864 and 3,879 kcal/kg DM, respectively) were similar, but the ME of corn
      was higher (P < 0.05) than the ME of field peas (3,825 vs. 3,741 kcal ME/kg DM).
      The results from the current experiments demonstrate that the nutrients in South
      Dakota-grown field peas are highly digestible by growing pigs. Therefore, such
      field peas may be included in diets for nursery pigs and growing-finishing pigs
      in amounts of at least 18 and 36%, respectively, without negatively affecting pig
      performance.

PMID- 15446473
TI  - Compensatory growth and nitrogen balance in grower-finisher pigs.
AB  - Sixteen castrated male pigs (averaging 21.2 +/- 4.9 kg) were used in two trials
      to investigate the effect of dietary amino acid content during the grower phase
      on growth performance and N balance. In each trial, pigs were assigned randomly
      to corn-soybean meal grower diets formulated to contain 5.0 or 11.0 g lysine/kg
      (as-fed basis). Common Finisher 1 and 2 diets were offered when pigs reached 51.2
      +/- 3.3 and 79.5 +/- 3.4 kg, respectively. Pigs were placed in metabolism crates
      for a 9-d period during each of the grower, Finisher 1, and Finisher 2 phases
      when they weighed 43.3 +/- 3.9, 70.4 +/- 4.9, and 90.5 +/- 3.8 kg, respectively,
      to determine N balance. Blood samples were taken from each pig periodically after
      an overnight fast. Pigs were allowed ad libitum access to feed and water, except
      during the three adaptation/collection periods. There were no diet x trial
      interactions; thus, the data were combined. Pigs fed the low-amino acid grower
      diet grew more slowly and less efficiently (P < 0.001) during the grower phase
      and had more ultrasound backfat (P = 0.010) at the end of the grower phase than
      those fed the high-amino acid grower diet. During the Finisher 1 phase, however,
      pigs fed the low-amino acid diet grew more efficiently (P = 0.012) than those fed
      the high-amino acid diet, and the grower diet had no effect on overall weight
      gain, carcass traits, lean accretion, or meat quality scores. Although pigs fed
      the low-amino acid diet had less serum urea N (P < 0.001) and more glucose (P =
      0.009) at 43.3 kg, there seemed to be no clear, long-term effect of the grower
      diet on serum metabolites. During the grower phase, pigs fed the high-amino acid
      diet consumed more N (P < 0.001), had higher apparent N digestibility (P =
      0.041), N utilization (P = 0.027), and N retention (P < 0.001), and excreted more
      fecal (P = 0.034) and urinary (P < 0.001) N than those fed the low-amino acid
      diet. Pigs fed the low-amino acid grower diet, however, had a higher N
      utilization (P = 0.024) during the Finisher 1 phase, and excreted less urinary N
      during both the Finisher 1 (P = 0.029) and 2 (P = 0.027) phases than those fed
      the high-amino acid grower diet. These results indicate that pigs subjected to
      early dietary amino acid restrictions compensated completely and decreased N
      excretion during both the restriction and realimentation phases. Compensatory
      growth can, therefore, have a positive effect not only on the overall efficiency
      of pig production but also on environment.

PMID- 15446474
TI  - Effect of feather meal on barrow performance.
AB  - One hundred ninety-six crossbred barrows of high lean gain potential (21.2 kg BW)
      were used in an experiment to determine the effect of dietary feather meal (FM)
      on barrow performance, specifically, the effects of the ingredient on ADG and
      carcass leanness. Additionally, 28 gilts (26.8 kg BW) were used to compare gender
      differences on the corn-soybean meal control diets. Treatments were control
      barrows and control gilts fed corn-soybean meal diets, and barrows fed according
      to a 2 x 3 factorial arrangement of FM levels (10 or 20%, as-fed basis) and
      starting weights on the diets (36, 60, or 86 kg BW). All barrow diets were
      formulated to contain the same apparent digestible lysine and ME. Control barrows
      ate more feed (2.61 vs. 2.39 kg/d; as-fed), grew faster (0.911 vs. 0.827 kg/d),
      had greater backfat depth at slaughter (15.6 vs. 11.6 mm), and had lower carcass
      lean content (P < 0.001), with no difference in daily lean gain (P = 0.848)
      compared with gilts. There was a linear (P = 0.010) decrease in ADG for barrows
      fed increasing amounts of FM from 36 kg BW to slaughter, with no effect of FM
      additions on ADG when initiated at 60 or 86 kg BW. There was a quadratic
      reduction (P = 0.008) in ADFI and estimated digestible lysine intake with
      increasing FM for the 36 to 60 kg BW period for barrows fed FM starting at 36 kg
      BW. There was a linear (P = 0.006) decrease in ADFI for the 60 to 86 kg BW period
      with increasing FM for barrows started on FM at 60 kg BW. There was no effect of
      experimental diets or starting weight on barrow 10th-rib backfat depth at
      slaughter. These results suggest that diets containing 10 and 20% FM were
      effective in decreasing overall ADG and ADFI by barrows when feeding of FM was
      initiated at 36 kg BW; however, backfat at slaughter was still greater than for
      control gilts.

PMID- 15446475
TI  - Technical note: comparison of Raman, mid, and near infrared spectroscopy for
      predicting the amino acid content in animal meals.
AB  - The objective of this study was to compare three infrared spectroscopy techniques
      for routine evaluation of AA in animal meals. Animal meals (n = 54) with known AA
      contents were scanned with a near (NIRS), mid (FTIR), and Raman infrared
      spectrometer. For NIRS and Raman, samples were scanned "as is", whereas for FTIR,
      samples had to be finely ground before scanning to obtain reasonable spectra.
      Both FTIR and Raman data suffered from noise; for Raman, this prevented the
      development of calibrations. Using derivatized spectral data and a standardized
      outlier removal procedure, calibrations for nutritionally relevant AA could be
      developed that were equivalent for both NIRS and FTIR. The variation across AA
      tested explained (r2) by these calibrations was 70% for NIRS and 68 + 3% for
      FTIR. Removing spectral data between 4,000 and 2,000 cm(-1) from the FTIR data
      improved calibrations (P = 0.09) and explained an average of 77% of the variation
      with prediction errors lower than obtained with NIRS (P < 0.01). However, FTIR
      calibrations based on the entire or the shortened spectrum contained fewer
      samples than did NIRS calibrations (41 and 39 vs. 48, respectively; P < 0.01)
      because more samples were removed as outliers. In conclusion, Raman did not yield
      acceptable spectra for animal meals. For FTIR, sample preparation was more time
      consuming because the samples required grinding before analysis. Using the entire
      mid-infrared range, FTIR calibrations were comparable to NIRS calibrations.
      Calibrations for FTIR were improved by eliminating wave numbers that exhibited
      more noise, resulting in prediction errors better than those for NIRS. Thus, FTIR
      has the potential to yield better calibrations for AA in animal meals than NIRS,
      but it requires greater care in sample preparation and scanning.

PMID- 15446476
TI  - Effects of emulsification, fat encapsulation, and pelleting on weanling pig
      performance and nutrient digestibility.
AB  - Two experiments were conducted to evaluate the effect of lysolecithin on
      performance and nutrient digestibility of nursery pigs and to determine the
      effects of fat encapsulation by spray drying in diets fed in either meal or
      pelleted form. In Exp. 1, 108 pigs (21 d of age; 5.96 +/- 0.16 kg BW) were
      allotted to one of four dietary treatments (as-fed basis): 1) control with no
      added lard, 2) control with 5% added lard, 3) treatment 2 with 0.02%
      lysolecithin, and 4) treatment 2 with 0.1% lysolecithin in a 35-d experiment.
      Added lard decreased ADG (P = 0.02) and ADFI (P < 0.06) during d 15 to 35 and
      overall. Lysolecithin improved ADG linearly (P = 0.04) during d 15 to 35 and
      overall, but did not affect ADFI or G:F. Addition of lard decreased the
      digestibility of DM (P = 0.10) and CP (P = 0.05) and increased (P = 0.001) fat
      digestibility when measured on d 10. Lysolecithin at 0.02%, but not 0.10%, tended
      to improve the digestibility of fat (P = 0.10). On d 28, digestibilities of DM,
      fat, CP, P, (P = 0.001), and GE (P = 0.03) were increased with the addition of
      lard, and lysolecithin supplementation linearly decreased digestibilities of DM
      (P = 0.003), GE (P = 0.007), CP, and P (P = 0.001). In Exp. 2, 144 pigs (21 d of
      age, 6.04 +/- 0.16 kg BW) were allotted to one of six treatments in a 3 x 2
      factorial randomized complete block design. Factors included 1) level (as-fed
      basis) and source of fat (control diet with 1% lard; control diet with 5%
      additional lard; and control diet with 5% additional lard from encapsulated,
      spray-dried fat) and 2) diet form (pelleted or meal). Addition of lard decreased
      feed intake during d 0 to 14 (P = 0.04), d 15 to 35 (P = 0.01), and overall (P =
      0.008), and improved G:F for d 15 to 35 (P = 0.04) and overall (P = 0.07).
      Encapsulated, spray-dried lard increased ADG (P = 0.004) and G:F (P = 0.003)
      during d 15 to 28 compared with the equivalent amount of fat as unprocessed lard.
      Pelleting increased ADG (P = 0.006) during d 0 to 14, decreased feed intake
      during d 15 to 35 (P = 0.01), and overall (P = 0.07), and increased G:F during
      all periods (P < 0.02). Fat digestibility was increased (P = 0.001) with
      supplementation of lard, and this effect was greater when diets were fed in meal
      form (interaction, P = 0.004). Pelleting increased the digestibility of DM, OM,
      and fat (P < 0.002). Results indicate that growth performance may be improved by
      lysolecithin supplementation to diets with added lard and by encapsulation of
      lard through spray drying.

PMID- 15446477
TI  - Bioefficacy of L-lysine sulfate compared with feed-grade L-lysine-HCl in young
      pigs.
AB  - A pig growth assay was conducted to determine the relative biological value (RBV)
      of lysine from L-lysine sulfate compared with feed-grade L-lysine HCl. One
      hundred nursery pigs with an average initial BW of 9.5 +/- 1.5 kg were blocked by
      BW and gender and allotted randomly to five dietary treatments in five replicates
      of four pigs per pen. A corn-peanut meal diet containing 0.6% total lysine (as
      fed basis) was supplemented with two levels (0.1 and 0.2%) of lysine from L
      lysine-HCl or L-lysine sulfate. The RBV of L-lysine sulfate was determined using
      multiple regression slope-ratio methodology, with ADG and G:F as the response
      criteria. At the tested levels, linear responses for gain and G:F were obtained
      from increments of lysine from the two lysine sources. When ADG was regressed on
      supplemental lysine intake, the RBV of lysine in L-lysine sulfate was 99% of the
      RBV of lysine in L-lysine HCl. When G:F was regressed on supplemental lysine
      intake, the RBV of lysine in L-lysine sulfate was 97% of the RBV of lysine in L
      lysine-HCl. The t-test analysis revealed that the RBV of lysine in L-lysine
      sulfate was not significantly different from the RBV of lysine in L-lysine HCl,
      which was assumed to be 100% bioavailable. In conclusion, L-lysine sulfate can
      replace L-lysine HCl in diets for growing swine.

PMID- 15446478
TI  - In vitro fermentation of various fiber and starch sources by pig fecal inocula.
AB  - Freeze-dried ileal effluent (1% wt/vol) from cannulated pigs fed rice-based diets
      with the inclusion of either animal protein (CON), animal protein plus potato
      starch (PS), animal protein plus sugar beet pulp (SBP), or animal protein plus
      wheat bran (WB) was incubated anaerobically at pH 6.0 in fermenters containing 5%
      (wt/vol) fecal slurry comprising mineral salts medium and 50 g/L of fresh feces
      from pigs fed the same diets as the cannulated pigs. Samples were collected from
      the fermenters at 0, 2, 4, 12, 24, and 48 h during in vitro fermentation for
      measuring nonstarch polysaccharides (NSP), starch, and short-chain fatty acids
      (SCFA). Results showed that the major SCFA produced were acetate, propionate, and
      butyrate. The inclusion of soluble dietary fiber (diet SBP) caused the highest
      concentrations of acetate, propionate, butyrate, and total SCFA, whereas the
      increase in the production of propionate resulting from the addition of insoluble
      dietary fiber (diet WB) only occurred at the initial stages during 48 h in vitro
      fermentation. At all sampling occasions (except for 4 h), the levels of butyrate
      were increased (P < 0.01) by resistant starch compared with fiber sources,
      showing that a higher level of butyrate can be achieved through microbial
      fermentation by potato starch. Lowered (P < 0.05) butyrate concentrations were
      observed with diet WB during in vitro fermentation. With the inclusion of fiber
      sources, the energy originating from SCFA was similar to that from NSP
      disappearance, whereas the values were lower (P < 0.05) from NSP disappearance
      than for SCFA generated without fiber sources supplemented. We conclude that more
      substrate is available in ileal effluent with the addition of soluble dietary
      fiber, and an increased level of butyrate could be achieved through microbial
      fermentation by resistant starch.

PMID- 15446479
TI  - Glycemic index of cracked corn, oat groats and rolled barley in horses.
AB  - Muscle glycogen synthesis depends on glucose availability. This study was
      undertaken to determine the glycemic and insulinemic response of horses to equal
      amounts of hydrolyzable carbohydrates (starch and sugar) in the form of one of
      three grain meals or intragastric administration of a glucose solution. In a
      randomized crossover design, seven horses were fed each of three grain meals
      (cracked corn, steamed oat groats, or rolled barley) or were infused
      intragastrically with glucose solution at 2 g of hydrolyzable carbohydrate
      (starch plus sugar) per kilogram of BW. The quantity of hydrolyzable carbohydrate
      ingested was not different among all treatments (P = 0.70). Plasma glucose
      concentration peaked in all four treatments by 1.5 to 2 h after feeding. Plasma
      glucose concentration remained higher than baseline in oat groats or barley-fed
      horses throughout 8 h, whereas plasma glucose returned to baseline by 5 to 6 h in
      corn-fed horses or after glucose administration. Meal consumption was slower in
      oat groats-fed horses than in corn-fed ones, which may confound the glycemic and
      insulinemic responses observed after grain feeding. Plasma glucose area under the
      curve (AUC) was 63% both in corn and oat groats and 57% in barley-fed horses
      compared with that of horses administered glucose (P = 0.13). Serum
      immunoreactive insulin concentration peaked between 2 and 3 h after feeding or
      glucose administration, and barley-fed horses had lower serum immunoreactive
      insulin concentration by 3 to 4 h than corn-fed horses or after glucose
      administration (P < 0.05). We conclude, in horses, ingestion of oat groats, corn,
      and barley result in similar plasma glucose AUC and, compared with the glycemic
      index of 100 as the glucose reference, corn, oat groats, and barley had a
      glycemic index of approximately 60.

PMID- 15446480
TI  - Effects of microbial phytase, low calcium and phosphorus, and removing the
      dietary trace mineral premix on carcass traits, pork quality, plasma metabolites,
      and tissue mineral content in growing-finishing pigs.
AB  - An experiment was conducted to determine the effects of phytase addition, reduced
      Ca and available P (aP), and removing the trace mineral premix (TMP) on growth
      performance, plasma metabolites, carcass traits, pork quality, and tissue mineral
      content in growing-finishing swine. One hundred twenty cross-bred pigs (initial
      and final BW of 22 and 109 kg, respectively) were allotted to five dietary
      treatments on the basis of weight within gender in a randomized complete block
      design. There were three replications of barrows and three replications of gilts,
      with four pigs per replicate pen. The dietary treatments were as follows: 1) corn
      soybean meal (C-SBM), 2) C-SBM with reduced Ca and aP, 3) C-SBM with reduced Ca
      and aP plus 500 phytase units/kg of diet, 4) Diet 1 without the TMP, and 5) Diet
      3 without the TMP. The Ca and aP were reduced by 0.10% in the low Ca and aP diets
      and the diets with added phytase. Daily gain, hot carcass weight, dressing
      percent, kilograms of carcass lean, bone ash percent, and bone strength were
      decreased (P = 0.10), but liver and kidney weight were increased (P = 0.10) in
      pigs fed diets with reduced Ca and aP; adding phytase reversed these responses (P
      = 0.10). The Commission Internationale de I'Eclairage L* was decreased (P = 0.09)
      in pigs fed the low Ca and aP diet plus phytase relative to those fed the control
      diet. Removing the TMP had no effect on overall growth performance, but it
      increased (P = 0.03) 10th-rib backfat thickness and fasting glucose and decreased
      (P = 0.03) carcass length and ham weight. Liver weight and liver weight as a
      percentage of final BW were not affected when phytase was added to the control
      diet, but removing the TMP increased liver weight and liver weight as a
      percentage of final BW; adding phytase reversed these responses (phytase x TMP, P
      = 0.06). Removing the TMP decreased (P = 0.08) Zn concentrations in the bone,
      muscle, and liver, and Cu and Fe concentrations in the bile but increased (P =
      0.08) Mn concentrations in the bile and liver of pigs. The addition of phytase
      reversed the negative effects of the reduced Ca and aP diets. These data indicate
      that removing the TMP in diets for growing-finishing pigs has no negative effects
      on growth performance or pork quality, but it had negative effects on carcass
      traits and had variable effects on tissue mineral content.

PMID- 15446481
TI  - Effect of hypothyroidism on the blood lipid response to higher dietary fat intake
      in mares.
AB  - Blood lipid and lipoprotein concentrations were measured and compared between
      euthyroid and thyroidectomized mares on low-fat or high-fat diets to test the
      hypothesis that hypothyroidism alters the blood lipid response to higher dietary
      fat intake. Four healthy adult mares and four adult mares that had been
      thyroidectomized 3 to 6 mo earlier were placed on low-fat or high-fat diets
      according to a replicated 2 x 2 Latin square design consisting of two 5-wk
      feeding periods separated by a 2-wk washout interval. Plasma lipid concentrations
      were measured at 0, 3, 4, and 5 wk, and plasma lipase activities were measured at
      the end of each 5-wk feeding period. Compared with euthyroid mares (0.46 ng/mL
      [range 0.34 to 0.68 ng/mL T3], and 21.5 ng/mL [range 18.1 to 25.1 ng/mL T4],
      respectively), median serum concentrations of T3 and T4 were lower (P = 0.029 and
      P = 0.021, respectively) in thyroid-ectomized mares (0.26 ng/mL [range 0.23 to
      0.26 ng/ mL T3], and undetectable T4). Serum T4 concentrations were below the
      limits of detection in thyroidectomized horses. Alterations in body weight over 5
      wk did not differ between groups. Mean plasma very low density lipoprotein (VLDL)
      and triglyceride (TG) concentrations were higher (P = 0.045 and 0.034,
      respectively) in hypothyroid mares (55.42 +/- 35.05 mg/dL and 52.83 +/- 34.46
      mg/dL, respectively) compared with euthyroid mares (28.28 +/- 13.76 mg/dL and
      23.53 +/- 9.84 mg/dL, respectively). Mean plasma total cholesterol (TC)
      concentrations increased from 88.73 +/- 25.49 mg/dL at baseline to 103.93 +/-
      24.42 mg/dL after 5 wk on the low-fat diet, but increased by a greater magnitude
      (P = 0.006 diet +/- time interaction) in mares that were on the high-fat diet
      (81.05 +/- 17.24 mg/dL and 123.84 +/- 32.27 mg/ dL, respectively). Mean plasma TC
      concentrations were higher (P = 0.099) in hypothyroid mares (116.16 +/- 32.89
      mg/dL) than in euthyroid mares (89.56 +/- 14.45 mg/ dL). Higher post-heparin
      plasma lipoprotein lipase and hepatic lipase activities (P = 0.012 andP = 0.017,
      respectively) were detected in mares that were on the high-fat diet (2.66 +/-
      0.91 micromol FA x mL(-1) x h(-1) and 2.95 +/- 0.49 micromol FA x mL(-1) x h(-1),
      respectively) vs. a low-fat diet (1.75 +/- 0.55 micromol FA x mL(-1) x h(-1) and
      2.27 +/- 0.59 micromol FA x mL(-1) x h(-1), respectively). We conclude that
      plasma VLDL and TG concentrations are elevated in hypothyroid mares, but the
      blood lipid response to higher dietary fat intake is not influenced by
      hypothyroidism.

PMID- 15446482
TI  - Effect of supplementation of xylanase and phospholipase to a wheat-based diet for
      weanling pigs on nutrient digestibility and concentrations of microbial
      metabolites in ileal digesta and feces.
AB  - The objective of this study was to determine the effect of supplementing a wheat
      based diet with xylanase and phospholipase either alone or in combination on the
      ileal and fecal digestibilities of nutrients and energy in early-weaned pigs. In
      addition, the concentrations of ammonia, lactate, and VFA were measured in ileal
      digesta and feces. The experiment was carried out with 16 barrows weaned at the
      age of 11 d with an average initial BW of 4.1 kg. On d 4 and 5 postweaning, the
      piglets were fitted with a simple T-cannula at the distal ileum. The experiment
      was designed as a balanced incomplete block design with three periods. The
      piglets received the basal diet with or without supplementation of either
      xylanase or phospholipase or a combination of these. There was a positive (P =
      0.005 to 0.018) effect on the digestibility values of GE, OM, CP, crude fiber
      (CF), and NDF with xylanase supplementation. Apart from lysine, threonine,
      cysteine, glycine, and proline, the digestibility values of all AA were improved
      (P = 0.001 to 0.024). Phospholipase supplementation had a positive effect on CP
      (P = 0.047) and CF (P = 0.002) digestibilities, but no effect on ether extract
      (EE) digestibility. Supplementation of both enzymes showed the largest response
      in nutrient digestibilities, except that EE digestibility was not affected. No
      differences were found in D-/L- lactate, and ammonia concentrations among
      treatments. Acetate and propionate concentrations tended to increase when
      xylanase was supplemented and were highest for the combination of both enzymes.
      Despite the positive effects on ileal nutrient and energy digestibilities, there
      was no effect of xylanase or the combined enzyme supplementation on the fecal
      digestibilities of OM, CP, EE, CF, NDF, ADF, or GE, and on fecal concentrations
      of VFA. Phospholipase alone slightly decreased the total-tract nutrient and
      energy digestibilities (P < 0.05). In conclusion, the combination of both enzymes
      generally led to the highest increases in ileal digestibilities, which were of
      small numerical magnitude (approximately 2%). However, on a relative basis, this
      increase of 2% represents approximately 13% of the remaining diet that was
      available for digestion based on the fact that approximately 15% of the diet was
      not digested in the control pigs. Thus, the potential benefits in the nutrition
      of weanling pigs from combinations of enzymes should be validated under practical
      conditions.

PMID- 15446483
TI  - The efficacy of an Escherichia coli-derived phytase preparation.
AB  - Five experiments were conducted to evaluate the effect of an Escherichia coli
      derived phytase on phytate-P use and growth performance by young pigs. The first
      experiment involved time course, pH dependence, and phytase activity studies to
      investigate the in vitro release of P from corn, soybean meal, and an inorganic P
      unsupplemented corn-soybean meal negative control diet. In Exp. 2, which was
      designed to determine the efficacy of the E. coli-derived vs. fungal phytase
      added diets at 0, 250, 500, 750, 1,000, or 1,250 FTU/kg (as-fed basis; one
      phytase unit or FTU is defined as the quantity of enzyme required to liberate 1
      micromol of inorganic P/min, at pH 5.5, from an excess of 15 microM sodium
      phytate at 37 approximately C) and a positive control diet, eight individually
      penned 10-kg pigs per diet (12 diets, 96 pigs) were used in a 28-d growth study.
      The third experiment was a 10-d nutrient balance study involving six 13-kg pigs
      per diet (four diets, 24 pigs) in individual metabolism crates. In Exp. 4, eight
      pens (four pigs per pen) of 19-kg pigs per treatment were used in a 42-d growth
      performance study to examine the effect of adding the E. coli-derived phytase to
      corn-soybean diets at 0, 500, or 1,000 FTU/kg (as-fed basis) and a positive
      control (four diets, 128 pigs). In Exp. 5, six 19-kg pigs per treatment were used
      in a 10-d nutrient balance study to investigate the effects of the E. coli
      derived phytase added to diets at 0, 250, 500, 750, or 1,000 FTU/kg (as-fed
      basis) and a positive control diet (six diets, 36 pigs). The in vitro study
      showed that the E. coli-derived phytase has an optimal activity and pH range of 2
      to 4.5. Inorganic phosphate release was greatest for soybean meal, least for
      corn, and intermediate for the negative control diet. Dietary supplementation
      with graded amounts of E. coli-derived phytase resulted in linear increases (P <
      0.05) in weight gain, feed efficiency, and plasma Ca and P concentrations in 10
      kg pigs in Exp. 2. Phytase also increased P digestibility and retention in the 13
      kg pigs in Exp. 3. In Exp. 4, dietary supplementation with E. coli-derived
      phytase resulted in linear increases (P < 0.05) in weight gain and feed
      efficiency of 19-kg pigs. Supplementation of the diets of 19-kg pigs with the E.
      coli-derived phytase also improved Ca and P digestibility and retention in Exp.
      5. In the current study, the new E. coli-derived phytase was efficacious in
      hydrolyzing phytate-P, both in vitro and in vivo, in young pigs.

PMID- 15446484
TI  - Effect of energy source and ruminally degradable protein addition on performance
      of lactating beef cows and digestion characteristics of steers.
AB  - Two trials were conducted to determine the effect of energy source (ENG) and
      ruminally degradable protein (RDP) on lactating cow performance and intake and
      digestion in beef steers. In Trial 1, 78 cow-calf pairs were used in a 2 x 2
      factorial design to determine the effect of ENG (corn or soyhulls; SH) and RDP
      (with our without sunflower meal) to a forage diet for lactating beef cows. The
      basal diet consisted of 75% grass hay (11.5% CP) and 25% wheat straw (7.4% CP).
      Supplement treatments and predicted RDP balances were corn (-415 g of RDP/d); SH
      (-260 g of RDP/d); corn plus RDP (0 g of RDP/d); or SH plus RDP (0 g of RDP/d).
      Data were analyzed as a split-plot in time, with pen as the experimental unit
      (two pens per treatment). No interaction between ENG and RDP was present (P >
      0.08) for any response variable. No differences (P > 0.39) due to ENG or RDP were
      noted for BW, BCS, or milk yield; however, final calf weight tended to increase
      with ENG (P = 0.06). In Trial 2, a 5 x 5 Latin square was used to determine
      effects of ENG and RDP on intake and digestion in steers (686 +/- 51 kg BW).
      Treatments were arranged as a 2 x 2 plus one factorial and comprised a control
      (CON; grass hay, 7% CP), grass hay plus 0.4% BW SH, grass hay plus 0.4% BW SH and
      0.15% BW sunflower meal, grass hay plus 0.4% BW corn, and grass hay plus 0.4% BW
      corn and 0.2% BW sunflower meal. Preplanned contrasts included main effects of
      ENG and RDP, ENG x RDP interaction, and CON vs. supplemented (SUP) treatments.
      Supplementation increased total DMI compared with CON (P = 0.001), but forage DMI
      was greater (P = 0.001) for CON than for SUP. An ENG x RDP interaction occurred
      for forage DMI (P = 0.02); addition of RDP to corn decreased forage intake,
      whereas addition of RDP to SH had no effect. There was an ENG x RDP interaction
      (P = 0.001) for ruminal pH; pH tended to increase with RDP addition to SH (P =
      0.07), but decreased with RDP addition to corn (P = 0.001). Supplementation
      increased ruminal ammonia compared with CON (P = 0.001). Likewise, RDP increased
      ruminal ammonia (P = 0.001). An interaction occurred for OM disappearance (OMD; P
      = 0.01). The RDP addition to SH numerically decreased OMD (P = 0.23), whereas RDP
      addition to corn numerically increased OMD (P = 0.14). Intake and digestion seem
      to respond differently to RDP addition depending on supplemental energy source.
      Both corn or SH seem to be suitable supplements for the quality of forage used in
      this trial. Addition of supplemental protein did not improve cow or calf
      performance.

PMID- 15446485
TI  - Value of sunflower seed in finishing diets of feedlot cattle.
AB  - The value of sunflower seed (SS) in finishing diets was assessed in two feeding
      trials. In Exp. 1, 60 yearling steers (479 +/- 45 kg) were fed five diets (n =
      12). A basal diet (DM basis) of 84.5% steam-rolled barley, 9% barley silage, and
      6.5% supplement was fed as is (control), with all the silage replaced (DM basis)
      with rolled SS, or with grain:silage mix replaced with 9% whole SS, 14% whole SS,
      or 14% rolled SS. Liver, diaphragm, and brisket samples were obtained from each
      carcass. In Exp. 2, 120 yearling steers (354 +/- 25 kg) were fed corn- or barley
      based diets containing no SS, high-linoleic acid SS, or high-oleic acid SS (a 2 x
      3 factorial arrangement, n = 20). Whole SS was included at 10.8% in the corn
      based and 14% in the barley-based diets (DM basis). In Exp. 1, feeding whole SS
      linearly increased DMI (P = 0.02), ADG (P = 0.01), and G:F (P = 0.01). Regression
      of ME against level of whole SS indicated that SS contained 4.4 to 5.9 Mcal
      ME/kg. Substituting whole for rolled SS did not significantly alter DMI, ADG, or
      G:F (8.55 vs. 8.30 kg/d; 1.36 vs. 1.31 kg; and 0.157 vs. 0.158, respectively).
      Replacing the silage with rolled SS had no effect on DMI (P = 0.91) but
      marginally enhanced ADG (P = 0.10) and improved G:F (P = 0.01). Dressing percent
      increased linearly (P = 0.08) with level of SS in the diet. Feeding SS decreased
      (P < 0.05) levels of 16:0 and 18:3 in both diaphragm and subcutaneous fats, and
      increased (P = 0.05) the prevalence of 18:1, 18:2, cis-9,trans-11-CLA and trans
      10,cis-12-CLA in subcutaneous fat. In Exp. 2, barley diets supplemented with high
      linoleic SS decreased DMI (P = 0.02) and ADG (P = 0.007) by steers throughout the
      trial, whereas no decrease was noted with corn (interaction P = 0.06 for DMI and
      P = 0.01 for ADG). With barley, high-linoleic SS decreased final live weight (554
      vs. 592 kg; P = 0.01), carcass weight (329 vs. 346 kg; P = 0.06), and dressing
      percent (58.5 vs. 59.4%; P = 0.04). Steers fed high-linoleic SS plus barley had
      less (P < 0.05) backfat than those fed other SS diets. No adverse effects of SS
      on liver abscess incidence or meat quality were detected. Although they provide
      protein and fiber useful in formulating finishing diets for cattle, and did
      improve performance in Exp. 1, no benefit from substituting SS for grain and
      roughage was detected in Exp. 2. Because of unexplained inconsistencies between
      the two experiments, additional research is warranted to confirm the feeding
      value of SS in diets for feedlot cattle.

PMID- 15446486
TI  - In vitro effects of individual fatty acids on protozoal numbers and on
      fermentation products in ruminal fluid from cattle fed a high-concentrate, barley
      based diet.
AB  - The objective of this study was to investigate the effects of sodium salts of
      individual fatty acids on protozoal numbers and ruminal fermentation variables in
      vitro. Ruminal inoculum was obtained from two heifers fed a finishing diet
      consisting of (DM basis) 90% rolled barley grain, 4% barley silage, 5% soybean
      meal, and 1% mineralized salt. Fatty acids (FA) were included individually in the
      inoculum as follows: C6:0, C8:0, and C10:0 at concentrations (wt/vol) of 0.0625,
      0.125, and 0.25%; C14:0 and C18:0 at concentrations of 0.125, 0.25, and 0.5%; and
      C12:0, C16:0, C18:1, C18:2, and C18:3 at concentrations of 0.25, 0.5, and 1.0%.
      15N-Labeled casein was included as a N tracer. In the presence of medium-chain
      saturated FA (particularly C10:0 and C12:0), no ciliate protozoa (99.8%Entodinium
      spp.) were recovered from the incubation medium. Long-chain unsaturated FA
      (C18:3, C18:2, C18:1) also decreased (P < 0.05) protozoal numbers. At all
      concentrations tested, C10:0 and C12:0 decreased (P < 0.05) ammonia and total VFA
      concentrations (by 29 and 22%, respectively) and increased (P < 0.05)
      concentrations of total free amino acids, reducing sugars, and soluble protein.
      At the greatest concentrations of these FA, xylanase and amylase activities of
      the incubation media were decreased (P < 0.05). The C18 unsaturated FA increased
      (P < 0.05) the polysaccharide-degrading activities of the media. These in vitro
      results suggest that long-chain unsaturated FA in combination with medium-chain
      saturated acids have the potential to decrease protozoal numbers and ruminal
      ammonia utilization in cattle fed high-grain diets.

PMID- 15446487
TI  - Effects of crude protein concentration and degradability on performance, carcass
      characteristics, and serum urea nitrogen concentrations in finishing beef steers.
AB  - Two experiments were conducted at two locations to determine the effects of
      dietary CP concentration and source on performance, carcass characteristics, and
      serum urea nitrogen (SUN) concentrations of finishing beef steers. British x
      Continental steers were blocked by BW (357 +/- 28 and 305 +/- 25 kg initial BW; n
      = 360 and 225; four and five pens per treatment in Exp. 1 and 2, respectively).
      Steam-flaked corn-based diets were arranged in a 3 x 3 factorial with three CP
      concentrations (11.5, 13, or 14.5% of DM) and three sources of supplemental CP (N
      basis): 100% urea; 50:50 blend of urea and cottonseed meal; or 100% cottonseed
      meal. Steers in both experiments were initially implanted with Ralgro and
      reimplanted with Revalor-S on d 56. Performance and carcass data were pooled
      across locations. Crude protein concentration x source interactions were not
      observed (P = 0.22 to 0.93) for performance and carcass data. Crude protein
      concentration affected ADG (P = 0.02) and carcass-adjusted (to a common dressing
      percent within location) ADG quadratically (P = 0.06). Increasing the
      concentration of supplemental urea linearly increased carcass-adjusted ADG and
      G:F (P < 0.05) and carcass-adjusted G:F (P < 0.001). Dry matter intake was not
      affected (P = 0.93) by either CP concentration or source. Hot carcass weight
      (HCW; P = 0.02), LM area (P = 0.05), and dressing percent (P = 0.03) increased
      linearly with increasing urea concentration, whereas increasing CP concentration
      quadratically affected HCW (P = 0.02), with a maximum at 13% CP. Differences in
      backfat thickness and yield grade were negligible across treatments. Neither
      marbling score nor percentage of carcasses grading USDA Choice was affected by CP
      concentration or source. At all times measured, SUN concentrations increased (P <
      0.05) with increasing CP concentration, but effects of CP source were small and
      variable across time. Results indicate that increasing CP concentrations from
      11.5 to 13% slightly increased ADG and carcass-adjusted ADG, whereas increasing
      the proportion of supplemental urea increased carcass-adjusted ADG, G:F, and
      carcass-adjusted G:F and increased HCW, LM area, and dressing percent. A CP
      concentration above 13% seemed detrimental to ADG and HCW. Serum urea N increased
      over time, with CP concentration having a greater effect than CP source.

PMID- 15446488
TI  - Effects of concentration and composition of wet corn gluten feed in steam-flaked
      corn-based finishing diets.
AB  - Two finishing experiments were conducted to determine the effects of
      concentration (Exp. 1) and composition of wet corn gluten feed (Exp. 2) in steam
      flaked corn-based diets on feedlot steer performance. In Exp. 1, 192 English x
      Continental crossbred steer calves (299 +/- 0.6 kg) were used in a completely
      randomized design with six dietary treatments (four pens per treatment).
      Treatments were six concentrations of wet corn gluten feed (Sweet Bran, Cargill
      Inc., Blair, NE; 0, 10, 20, 25, 30, and 35%) replacing steam-flaked corn (DM
      basis). All diets contained 10% corn silage, 5% supplement, and 3.5% tallow (DM
      basis). Gain efficiency and ADG were similar (P > 0.25) among treatments. Dry
      matter intake was lower (P < 0.10) with 0% wet corn gluten feed than with
      concentrations of 20, 25, and 35% WCGF. Dry matter intake did not differ among
      treatments containing wet corn gluten feed. In Exp. 2, 160 English x Continental
      crossbred steer calves (315 +/- 0.6 kg) were used in a completely randomized
      design with five dietary treatments (four pens/treatment). Treatments were
      assigned based on four ratios of steep to corn bran/germ meal mix in wet corn
      gluten feed plus a negative control (CON). Wet corn gluten feed was fed at 25% of
      the dietary DM and was made by mixing steep and corn bran/germ meal into the
      diet. The four concentrations of steep in wet corn gluten feed that comprised the
      ratios were 37.5, 41.7, 45.8, and 50% (DM basis), with the remaining proportion
      being the bran/germ meal mix. Bran/germ meal mix was comprised of 60% dry corn
      bran, 24% germ meal, and 16% fine-cracked corn (DM basis). All diets contained
      10% corn silage, 5% supplement, and 3.5% tallow (DM basis). Daily gain did not
      differ (P = 0.18) among treatments. Gain efficiency did not differ between CON
      and 50% steep; however, G:F was decreased (P < 0.05) for concentrations of 37.5,
      41.7, and 45.8% steep compared with CON. A linear improvement (P < 0.05) was
      observed for G:F as concentration of steep increased as a proportion of wet corn
      gluten feed. These data suggest that wet corn gluten feed can be used at
      concentrations up to 35% of the dietary DM without adversely affecting
      performance, and that steep has more energy than bran/germ meal in steam-flaked
      corn-based diets.

PMID- 15446489
TI  - Nonstructural carbohydrate supplementation of yearling heifers and range beef
      cows.
AB  - A digestion study with 28 yearling heifers (428 +/- 9.9 kg; Exp. 1) and a 2-yr
      winter grazing trial with 60 crossbred cows (552 +/- 6.9 kg; Exp. 2) were used to
      determine the effects of level of nonstructural carbohydrate (NSC)
      supplementation on intake and digestibility of low-quality forage. Treatments
      were as follows: 1) control, no supplement; 2) 0.32 kg of NSC (1.8 kg/d of
      soybean hulls and soybean meal; DM basis); 3) 0.64 kg of NSC (1.7 kg/d of wheat
      middlings; DM basis); and 4) 0.96 kg of NSC (1.7 kg/d of barley and soybean meal;
      DM basis). Supplements provided 0.34 kg of CP/d and 5.1 Mcal of ME/d. In Exp. 1,
      heifers were individually fed hay (5.5% CP, DM basis) and their respective
      supplements in Calan gates for 28 d. Data were analyzed as a completely
      randomized design. In Exp. 2, cows were individually fed supplement on alternate
      days, and grazed a single rangeland pasture stocked at 1.8 ha/ animal unit month.
      Two ruminally cannulated cows were used per treatment to obtain forage extrusa
      and to measure in situ DM disappearance (DMD) and carboxymethylcellulase (CMCase)
      activity of particle-associated ruminal microbes. Data were analyzed as a
      completely randomized design with the effects of treatment, year, and their
      interaction. In both experiments, Cr2O3 boluses were used to determine fecal
      output, individual animal was the experimental unit, and contrasts were used to
      test linear and quadratic effects of NSC level and control vs. supplemented
      treatments. In Exp. 1, hay and diet DM, NDF, and CP intakes and digestibilities
      were increased (P < 0.01) by NSC supplementation compared with the control. In
      Exp. 2, 72-h in situ DMD and CMCase were decreased linearly (P < 0.08) with
      increasing NSC supplementation. Intake of forage DM, NDF, and CP was decreased
      linearly (P < 0.01) with increasing NSC supplementation during both years.
      Supplementation with NSC decreased (P = 0.01) cow BW loss compared with the
      control in yr 1, whereas in yr 2, cow BW loss was linearly increased (P = 0.03)
      by increasing NSC supplementation. Supplements containing NSC improved forage
      digestion and intake when heifers consumed forage deficient in CP relative to
      energy (digestible OM:CP > 7), but decreased forage digestion and intake when
      cows grazed forage with adequate CP relative to energy (digestible OM:CP < 7).
      Forage and supplement digestible OM:CP seemed to be superior predictors of
      response to supplementation with NSC compared with forage CP levels alone.

PMID- 15446490
TI  - Feeding encapsulated ground full-fat soybeans to increase polyunsaturated fat
      concentrations and effects on flavor volatiles in fresh lamb.
AB  - This research assessed the potential of increasing PUFA concentrations and the
      effect on flavor volatiles in red meat by feeding ground, full-fat soybean
      supplemented in casein complex. Supplements consisted of untreated ground, full
      fat soybean (CO) or ground, full-fat soybeans treated with acetaldehyde (AC) or
      diacetyl (DA) to form gels. On a DM basis, the control (CO), AC, and DA
      supplements contained 48.6, 50.0, and 49.1% CP and 17.3, 17.3, and 17.4% fat,
      respectively. Weaned feeder lambs (n = 18) were divided into three treatment
      groups with two pens of three lambs per group. One of three supplements (200 g of
      DM) plus 1 kg DM of a ground corn basal diet and 0.36 kg DM of grass hay was fed
      daily to each of six lambs in a group for 9 wk. Samples of the intramuscular
      (LM), intermuscular, subcutaneous, and kidney fat were obtained from each lamb
      carcass for determination of total lipid contents and fatty acid profiles. Flavor
      volatiles of broiled LM were also analyzed. Total fat content of the LM was 3.7,
      4.6, and 2.6% for lambs consuming diets supplemented with CO, AC, and DA,
      respectively. Compared with lambs fed the untreated supplement (CO), lambs
      supplemented with AC or DA had 1) higher (P < 0.05) concentrations of linoleic
      (4.80 vs. 6.37 or 6.80%) and linolenic (0.28 vs. 0.43 or 0.45%) acids in the LM
      nonpolar lipids; 2) a higher (P < 0.05) concentration of linoleic acid (22.1 vs.
      27.1 or 25.6%), but a lower (P < 0.05) concentration of oleic acid (17.2 vs. 13.0
      or 13.1%), in the LM polar lipids; 3) a higher (P < 0.05) concentration of
      linoleic acid (3.77 vs. 6.13 or 6.06%) in subcutaneous fat; and 4) higher (P <
      0.05) concentrations of linoleic (4.46 vs. 7.65 or 7.13%), linolenic (0.50 vs.
      0.85 or 0.80%), and stearic (24.9 vs. 27.2 or 26.9%) acids, but a lower (P <
      0.05) concentration of oleic acid (39.1 vs. 35.4 or 36.3%), in kidney fat. In
      broiled LM chops, 21 volatiles were identified, including seven alkanals, seven 2
      alkenals, two 2,4-alkadienals, and five other compounds, but most differences in
      the volatile concentrations among lambs fed the different supplements did not
      correspond to concentration differences in their precursor fatty acids. Results
      indicated that compared with the untreated supplement (CO), AC and DA supplements
      protected linoleic (C 18:2n6) and linolenic (C18:3n3) acids in soybean oil from
      degradation in the rumen of the lambs, resulting in increased deposition in the
      muscle and adipose tissues of lamb.

PMID- 15446491
TI  - The effects of poultry meal source and ash level on nursery pig performance.
AB  - Weanling pigs (total of 560) were used in two experiments to determine the
      effects of poultry meal in nursery diets on pig performance. In Exp. 1,210
      barrows and gilts (initially 7.4 kg and 21 +/- 2 d of age) were fed one of five
      diets, which included a control diet with no specialty protein products or (as
      fed basis) the control with 2.5 or 5.0% fish meal, or 2.9 or 5.9% poultry meal
      (11.8% ash). Poultry meal replaced fish meal on an equal lysine basis. Overall (d
      0 to 28), pigs fed diets containing fish meal had greater (P < 0.01) ADG than
      pigs fed poultry meal. Increasing fish meal tended to have increased (quadratic,
      P < 0.07) ADG, with the greatest improvement observed in pigs fed the diet
      containing 2.5% fish meal. Pigs fed diets containing fish meal had improved (P <
      0.01) G:F compared with pigs fed diets containing poultry meal. In Exp. 2, a
      total of 350 barrows and gilts (initially 8.9 kg and 22 +/- 2 d of age) were fed
      one of seven experimental diets, which included a control diet with no specialty
      protein products, or the control with 2.5 or 5.0% fish meal, 2.9 or 5.8% low-ash
      (10.9%) poultry meal, and 3.1 or 6.2% high-ash (13.5%) poultry meal. Poultry meal
      replaced fish meal on an equal lysine basis. Overall (d 0 to 15), there were no
      differences in ADG and ADFI (P = 0.14); however, pigs fed diets containing fish
      meal or poultry meal had improved (linear, P < 0.01) G:F compared with pigs fed
      the control diet. Pigs fed diets containing low-ash poultry meal had greater (P <
      0.01) G:F compared with pigs fed diets containing high-ash poultry meal. Based on
      these data, quality control specifications, such as ash content, need to be
      considered when using poultry meal as an animal protein replacement in diets for
      nursery pigs.

PMID- 15446492
TI  - Physiological responses in swine treated with water containing sodium bicarbonate
      as a prophylactic for gastric ulcers.
AB  - Maintenance of gastric pH above 4.0 aids the prevention of bile acid-mediated
      ulcerative damage to the pars esophageal tissue in pigs. One means of doing so is
      the addition of buffering compounds, such as sodium bicarbonate, to the water
      supply; however, any potential physiological effect of buffer consumption has yet
      to be determined. Experiment 1 tested the acute effects of buffer addition to the
      water supply on systemic acid-base and electrolyte balance in swine (BW 40.7 +/-
      3.0 kg). Consumption of water calculated to a 200 mOsm solution with sodium
      bicarbonate for 24 h increased (P < 0.05) blood Na+, HCO3(-), and pCO2, although
      these effects were all within physiologically tolerable levels. Urine pH and Na+
      excretion increased (P < 0.001) following the consumption of NaHCO3, with Na+
      concentration almost threefold higher in treated pigs compared with controls.
      Experiment 2 determined the chronic systemic effects of buffer consumption by
      measuring blood and urine variables, with pigs consuming NaHCO3-treated water
      throughout. Water consumption increased (P < 0.001) during buffer consumption,
      although intake levels remained within normal ranges. Blood pH levels were not
      affected by long-term consumption of dietary buffer; however, blood HCO3(-) (P <
      0.05), Na+, and pCO2 (P < 0.01) increased. Urine pH and urine Na+ concentration
      increased (P < 0.01) in buffer-treated compared with control animals. Results
      indicate that sodium bicarbonate can safely be added to the water supply for
      pigs, with no clinically relevant alterations in acid-base balance because the
      animals readily compensate for buffer intake.

PMID- 15446493
TI  - Maternal and reproductive performance of Brahman x Angus, Senepol x Angus, and
      Tuli x Angus cows in the subtropics.
AB  - To determine the maternal and reproductive performance of F1 cows in the
      subtropics, 42 Brahman x Angus, 34 Senepol x Angus, and 50 Tuli x Angus cows were
      bred to Angus bulls to calve first and subsequently bred to Charolais bulls to
      calve as 3- to 8-yr-olds. Age at first calving did not differ among crossbred
      cows. Angus-sired calf birth weights were heavier (P < 0.01) from Senepol x Angus
      than either Brahman x Angus or Tuli x Angus cows. Weaning weights of Angus-sired
      calves were heavier (P < 0.01) from Brahman x Angus (213.5 kg) than either
      Senepol x Angus (194.9 kg) or Tuli x Angus (191.5 kg) cows. As 3- to 8-yr-old
      cows, calf birth weights were heavier (P < 0.05) from Senepol x Angus compared
      with Brahman x Angus but not Tuli x Angus cows. Weaning weights of Charolais
      sired calves were heaviest (P < 0.05) from Brahman x Angus cows (268.9 kg),
      lightest from Tuli x Angus cows (233.4 kg), and intermediate from Senepol x Angus
      cows (245.0 kg). Calf crop born and calf crop weaned were lowest (P < 0.05) for
      Senepol x Angus cows (76.9 and 70.2%) and did not differ between Brahman x Angus
      (89.0 and 86.1%) and Tuli x Angus (94.7 and 86.5%) cows. Tuli x Angus cows tended
      (P < 0.10) to have a lower percentage of unassisted births and lower (P < 0.10)
      calf survival to weaning than Brahman x Angus cows but not Senepol x Angus cows.
      As 3- to 8-yr-olds, weaning weight per cow exposed was greatest (P < 0.05) for
      Brahman x Angus (234.2 kg), least (P < 0.05) for Senepol x Angus (173.0 kg), and
      intermediate (P < 0.05) for Tuli x Angus (209.1 kg) cows. Also as 3- to 8-yr
      olds, efficiency (205-d calf weight per 100 kg of cow exposed) was similar for
      Brahman x Angus (42.2) and Tuli x Angus cows (40.7), and both were greater (P <
      0.01) than for Senepol x Angus cows (33.8). These data indicate that, in the
      subtropics, maternal and reproductive performance of Tuli x Angus cows, but not
      Senepol x Angus cows, was comparable to Brahman x Angus cows, except for lower
      calf survivability and weaning weight.

PMID- 15446494
TI  - Morbidity effects on productivity and profitability of stocker cattle grazing in
      the Southern Plains.
AB  - Effects of bovine respiratory disease (BRD) on stocker cattle systems are unknown
      under extensive rangeland environments. Three experiments were conducted to test
      the hypothesis that BRD-based morbidity is a major factor affecting the
      productivity and profitability of stocker cattle grazing Southern Plains
      rangelands. In Exp. 1 (658 male calves; average BW = 231 kg), 17% of the cattle
      were treated for BRD <8 d, 6% for 8 to 14 d, and 8% for >14 d. Morbid cattle had
      lower ADG than did healthy cattle (P < 0.10). Cattle requiring 14 d of
      pharmaceutical therapy gained less than cattle having <14 d therapy (P < 0.01).
      In Exp. 2, (279 steers and bulls; average BW = 216 kg), the ADG by steers (0.74
      kg x animal(-1) x d(-1)) was greater (P < 0.05) than by bulls castrated after
      arrival (0.64 kg x animal(-1) x d(-1)). Castration after arrival led to a 13.5%
      loss in daily gain and a 10.3% loss in season-long gain. More (P < 0.05) bulls
      castrated after arrival (60%) were morbid compared with steers (28%). In Exp. 3,
      633 heifers (average BW = 251 kg) were used to test the effects of morbidity on
      weight gain and reproduction. Heifers with lower initial weights exhibited
      increased (P < 0.05) morbidity. Heifers requiring two or more antibiotic
      treatments gained 0.03 kg/d less (P < 0.10) than did healthy heifers and had
      lower (P < 0.05) conception rates (66 vs. 81%). Conception rate in twice-treated
      heifers was 19% less than healthy heifers. Morbid heifers conceived 0.6 mo later
      (P < 0.05) than healthy heifers. Under the conditions of Exp. 1 and Exp. 2,
      morbidity decreased net returns 9.7 to 21.3% per animal. Adjusted gross returns
      per animal in Exp. 3 for replacement heifers were 3 to 7.8% less for morbid
      heifers.

PMID- 15446495
TI  - Effects of supplementing with calcium salts of palm oil fatty acids or
      hydrogenated tallow on ewe milk production and twin lamb growth.
AB  - Two experiments were conducted with Polypay ewes nursing twin lambs to evaluate
      the effects of supplementing fat (calcium salts of palm oil fatty acids or
      hydrogenated tallow) on ewe lactation. In Exp. 1, ewes were fed a 52%
      concentrate:48% hay-based diet (as-fed basis) consisting of alfalfa hay (n = 4),
      endophyte-free fescue hay (n = 4), or fescue hay with 3.7% fatty acids (n = 4)
      from d 4 to 56 of lactation. In Exp. 2, ewes were fed similar diets that had
      endophyte-free fescue hay (n = 6), fescue hay with 3.7% fatty acids (n = 5), or
      fescue hay with 3.1% tallow (n = 6) from d 14 before lambing until d 57 of
      lactation. Diet formulations with supplemental fat were more nutrient dense, and
      treatments were fed to meet ewe nutrient requirements; this caused diets with
      added fat to be offered at 10 and 17% lower rates than unsupplemented diets in
      Exp. 1 and 2, respectively. Lambs were maintained to consume only ewe milk. Ewe
      milk production and composition were determined using a portable milking machine
      following a 3-h separation from lambs. In Exp. 1, milk fat content was increased
      (P < 0.01) when ewes consumed fescue hay with fatty acids vs. the fescue hay diet
      (11.4 vs. 8.3%). Ewes fed fescue hay with fatty acids lost the most (P < 0.05)
      weight over lactation (-8.6 kg) compared with ewes fed the alfalfa hay (-2.4 kg)
      and fescue hay (-3.8 kg) diets. Other milk measures, lamb gain, and production
      efficiencies were not changed. In Exp. 2, ewes supplemented with fatty acids
      produced more (P < 0.05) milk fat than those fed tallow (290 vs. 210 g/d). The
      proportion of synthesized milk fat 14:0 was decreased (P < 0.01), but the
      percentage of incorporated 16:0 increased (P < 0.05) when fatty acids were fed.
      Dietary fat digestibility by ewes was increased (P < 0.01) by fatty acid
      supplementation but decreased (P < 0.01) when tallow was added. Although ewe
      weight measures were not changed in Exp. 2, twin lamb gain per ewe organic matter
      intake was most efficient (P < 0.05) when ewes were supplemented with fatty
      acids. Results suggest that feeding hydrogenated tallow decreased nutrient
      availability for ewe milk fat production. A complete diet based on endophyte-free
      fescue hay can replace a traditional alfalfa hay diet, whereas supplementing with
      the calcium salts of palm oil fatty acids may be more feasible when energy is
      limiting during ewe lactation.

PMID- 15446496
TI  - Effects of diet complexity and dietary lactose levels during three starter phases
      on postweaning pig performance.
AB  - Four experiments involving 1,005 crossbred pigs weaned at 19 +/- 2 d of age
      evaluated the effect of diet complexity and lactose level on starter pig
      performances. Experiment 1 was a randomized complete block (RCB) conducted in
      nine replicates with 135 pigs. A complex diet using several protein sources, a
      semicomplex diet with fewer protein sources, and a simple diet of corn and
      soybean meal comprised the three treatment groups. All diets contained 25%
      lactose (as-fed basis) with lysine (total) constant from d 0 to 14 (1.55%) and d
      14 to 28 (1.45%), respectively. Gain, feed intake, and feed efficiency (P < 0.05)
      improved as diet complexity increased during both periods. In Exp. 2, 240 pigs in
      eight replicates in a RCB design were fed complex diets, but dietary lactose
      (total; as-fed basis) levels ranged from 10 to 35% in 5% increments from 0 to 14
      d after weaning. From 14 to 30 d, a common 17% lactose diet was fed to evaluate
      the effects of early lactose level on subsequent responses. Gains (P < 0.05)
      increased for the 0- to 7- and 0- to 14-d periods as lactose increased to 30%.
      Similar gains resulted for all treatment groups from 14 to 30 d after weaning,
      with no evidence of compensatory responses to early lactose levels. In Exp. 3,
      330 pigs were fed complex diets. From 0 to 7 d after weaning, the diets contained
      25% lactose (as-fed basis), and from 7 to 21 d postweaning, the lactose levels
      ranged from 7 to 31% in 5% increments. Gain (P < 0.01) and feed efficiency (P <
      0.05) increased from 7 to 21 d to the 17% lactose level. In Exp. 4, 300 pigs were
      fed 25 and 17% (as-fed basis) lactose diets from 0 to 7 and 7 to 21 d
      postweaning, respectively. From 21 to 35 d postweaning, lactose levels of 0 to
      20% in 5% increments were added to a corn-soybean meal diet. The experiment was
      conducted as a RCB design in 12 replicates. Gain (P < 0.05) and feed intake (P <
      0.05) increased to 10 to 15% lactose. When the data from Exp. 4 were partitioned
      into lighter (15.0 kg) and heavier (17.7 kg) pig weight replicates, only the
      lighter replicates had significant improvements in gain, feed intake, and feed
      efficiency (P < 0.05) in response to dietary lactose. These results demonstrated
      that starter pigs performed better when fed complex diets, that dietary lactose
      levels of 25 to 30% (to 7 kg BW) during the initial week postweaning, 15 to 20%
      lactose during d 7 to 21 (to 12.5 kg BW), and 10 to 15% lactose during d 21 to 35
      postweaning (to 25 kg BW) resulted in maximum performance.

PMID- 15446497
TI  - The effect of body condition on disposition of alkaloids from silvery lupine
      (Lupinus argenteus pursh) in sheep.
AB  - Several species of lupine (Lupinus spp.) are poisonous to livestock, producing
      death in sheep and "crooked calf disease" in cattle. Range livestock cope with
      poisonous plants through learned foraging strategies or mechanisms affecting
      toxicant disposition. When a toxic plant is eaten, toxicant clearance may be
      influenced by the animal's nutritional and/or physiological status. This research
      was conducted to determine whether differences in body condition or short-term
      nutritional supplementation of sheep altered the disposition of lupine alkaloids
      given as a single oral dose of ground silvery lupine (Lupinus argenteus) seed.
      Ewes in average body condition (ABC, n = 9) and low body condition (LBC, n = 10)
      received a single dose of ground lupine seeds including pods (8.5 g/kg BW) via
      gavage on the first day of the experiment, and were then randomly assigned to one
      of two nutritional supplement treatments. Blood samples were taken 0 to 60 h
      after dosing to compare blood alkaloid concentration and to evaluate alkaloid
      absorption and elimination profiles. Concentrations of total alkaloid and
      anagyrine, 5,6 dehydrolupanine, lupanine, and alkaloid E were measured in serum.
      These four alkaloids constituted 78 and 75% of the total alkaloid concentration
      in serum for LBC vs. ABC groups, respectively. Initial analysis indicated that
      short-term supplementation had no effect on alkaloid disposition, and
      supplementation was removed from the statistical model. The highest concentration
      of total alkaloids was observed 2 h after dosing. Overall, serum total alkaloid
      and anagyrine levels (area under the curve) were higher (P < 0.01) for sheep in
      the LBC group. Serum peak concentrations of total alkaloid and anagyrine were
      higher in LBC vs. ABC groups (P < 0.05). Serum elimination of anagyrine, unknown
      alkaloid E, and lupanine was decreased in LBC vs. ABC treatments (P < 0.05).
      These results demonstrate that body condition is important in the disposition of
      lupine alkaloids; however, further research is needed to determine the potential
      benefit, if any, that short-term nutritional supplementation might have on
      alkaloid disposition.

PMID- 15446498
TI  - Assessing attitudes toward farm animal welfare: a national survey of animal
      science faculty members.
AB  - A survey to measure attitudes toward farm animal welfare was developed. We
      targeted animal science faculty because of their influence on animal production
      in the United States. We initially interviewed 34 faculty members from a large
      Midwestern public university to assist with questionnaire development. After our
      written survey was developed, we pilot-tested our questionnaire at this same
      university. Thereafter, we sent an e-mail advance notice, first survey, and
      follow-up survey/thank-you to the national population of animal science faculty
      members. With an n = 446 (response rate = 45%), we observed the following: 51%
      (for layer birds), 58% (for meat birds), 66% (for swine), 84% (for dairy), 86%
      (for sheep), and 87% (for beef) of our respondents agreed that the predominant
      methods used to produce various types of animal products provided appropriate
      levels of animal welfare. Our findings showed that greater than 90% of
      respondents support general principles of animal welfare, such as keeping animals
      free from unnecessary fear and distress. However, specific practices that have
      been shown to elicit distress (e.g., castration without anesthetic) were deemed a
      concern by only 32% of the respondents. Various industry practices/outcomes were
      assessed for level of concern and varied from a high of 83% of respondents
      agreeing that flooring effects on lameness in intensively farmed animals are a
      concern, to a low of 16% agreeing that early weaning in pigs is a concern. Summed
      attitude scores showed significant relationships with the demographic variables
      of gender (P < 0.01) and political ideology (P < 0.01), with women and those
      holding more liberal political views being more concerned about farm animal
      welfare issues. Gaining an awareness of various stakeholders' attitudes (e.g.,
      animal scientists, veterinarians, producers, and consumers) toward farm animal
      welfare will assist animal welfare scientists in knowing which research topics to
      emphasize and, perhaps, where critical gaps in accessibility of knowledge exist.

PMID- 15446499
TI  - Impact of modern technology on graduate education in animal sciences.

PMID- 15446500
TI  - Design and hydrodynamic evaluation of a novel pulsatile bioreactor for
      biologically active heart valves.
AB  - Biologically active heart valves (tissue engineered and recellularized tissue
      derived heart valves) have the potential to offer enhanced function when compared
      to current replacement value therapies since they can possibly remodel, and grow
      to meet the needs of the patient, and not require chronic medication. However,
      this technology is still in its infancy and many fundamental questions remain as
      to how these valves will function in vivo. It has been shown that exposing
      biologically active tissue constructs to pulsatile pressures and flows during in
      vitro culture produces enhanced extracellular matrix protein expression and
      cellularity, although the ideal hydrodynamic conditioning regime is as yet
      unknown. Moreover, in vitro organ-level studies of living heart valves aimed at
      studying the remodeling processes require environments that can accurately
      reproduce in vivo hemodynamics under sterile conditions. To this end, we have
      developed a system to study the effects of subjecting biologically active heart
      valves to highly controlled pulsatile pressure and flow waveforms under sterile
      conditions. The device fits inside a standard incubator and utilizes a computer
      controlled closed loop feedback system to provide a high degree of control. The
      mean pressure, mean flow rate, driving frequency, and shape of the pulsatile
      pressure waveform can be changed automatically in order to simulate both
      physiologic and nonphysiologic hemodynamic conditions. Extensive testing and
      evaluation demonstrated the device's ability to subject a biologically active
      heart valve to highly controlled pulsatile waveforms that can be modulated during
      the course of sterile incubation.

PMID- 15446501
TI  - Miniature C-shaped transducers for chordae tendineae force measurements.
AB  - C-shaped strain gauge force transducers were designed to enable dynamic
      measurements of the tension of the individual mitral valve chordae tendineae
      during the cardiac cycle. The force transducers were constructed from a C-shaped
      brass ring with a diameter of 6 mm, width of 2 mm, thickness of 0.5 mm, and a
      mass of <80 mg. Miniature strain gauges elements were cemented onto the inner and
      outer side of the ring. The strain gauges were connected to thin Teflon wires and
      coupled in a Wheat-stone half-bridge circuit to a signal conditioner and
      amplifier. The transducer was coated with a resistive sealing ensuring electrical
      insulation as well as mechanical protection. Technical testings of sensitivity,
      linearity, noise level, and frequency response characteristics demonstrated that
      the transducers were suitable for dynamic chordal force measurements performed
      under in vitro and in vivo experimental conditions.

PMID- 15446502
TI  - Flow-induced platelet activation in bileaflet and monoleaflet mechanical heart
      valves.
AB  - A study was conducted to measure in vitro the procoagulant properties of
      platelets induced by flow through Carbomedics bileaflet and Bjork-Shiley
      monoleaflet mechanical heart valves (MHVs). Valves were mounted in a left
      ventricular assist device, and platelets were circulated through them under
      pulsatile flow. Platelet activation states (PAS) were measured during circulation
      using a modified prothrombinase method. Computational fluid dynamics (CFD)
      simulations of turbulent, transient, and non-Newtonian blood flow patterns
      generated by the two valve designs were done using the Wilcox k - w turbulence
      model, and platelet shear-stress histories (the integral of shear-stress exposure
      with respect to time) through the two MHVs were calculated. PAS measurements
      indicated that the bileaflet MHV activated platelets at a rate more than twice
      that observed with the monoleaflet MHV. Turbulent flow patterns were evident in
      CFD simulations for both valves, and corroborated the PAS observations, showing
      that, for particles close to the leaflet(s), shear-stress exposure in the
      bileaflet MHV can be more than four times that in the monoleaflet valve.

PMID- 15446503
TI  - Noninvasive measurement of steady and pulsating velocity profiles and shear rates
      in arteries using echo PIV: in vitro validation studies.
AB  - Although accurate measurement of velocity profiles, multiple velocity vectors,
      and shear stress in arteries is important, there is still no easy method to
      obtain such information in vivo. We report on the utility of combining ultrasound
      contrast imaging with particle image velocimetry (PIV) for noninvasive
      measurement of velocity vectors. This method (echo PIV) takes advantage of the
      strong backscatter characteristics of small gas-filled microbubbles (contrast)
      seeded into the flow. The method was tested in vitro. The steady flow analytical
      solution and optical PIV measurements (for pulsatile flow) were used for
      comparison. When compared to the analytical solution, both echo PIV and optical
      PIV resolved the steady velocity profile well. Error in shear rate as measured by
      echo PIV (8%) was comparable to the error of optical PIV (6.5%). In pulsatile
      flow, echo PIV velocity profiles agreed well with optical PIV profiles. Echo PIV
      followed the general profile of pulsatile shear stress across the artery but
      underestimated wall shear at certain time points. However, error in shear from
      echo PIV was an order of magnitude less than error from current shear measurement
      methods. These studies indicate that echo PIV is a promising technique for
      noninvasive measurement of velocity profiles and shear stress.

PMID- 15446504
TI  - Influence of progressive central hypovolemia on Holder exponent distributions of
      cardiac interbeat intervals.
AB  - The purpose of the study was to determine the dependency of the statistical
      properties of the R to R interval (RRI) time series on progressive central
      hypovolemia with lower body negative pressure. Two data-processing techniques
      based on wavelet transforms were used to determine the change in the
      nonstationary nature of the RRI time series with changing negative pressure. The
      results suggest that autonomic neural mechanism driving cardiac interbeat
      intervals during central hypovolemia go through various levels of
      multifractality, as determined by Holder exponent distributions.

PMID- 15446505
TI  - Age and sex dependent variations in the normal magnetocardiogram compared with
      changes associated with ischemia.
AB  - Magnetocardiography is the measurement of the magnetic fields of the heart. Human
      studies performed in magnetically shielded laboratories have demonstrated that
      magnetocardiograms (MCGs) can detect ischemia. The aim of this study was to
      obtain clinically useful MCGs in an unshielded hospital room. Other objectives
      included understanding the normal variations in MCG during repolarization and
      determining the MCG parameters that best discriminate patients with ischemia from
      healthy controls. We measured 51 healthy volunteers of both sexes from 25 to 76
      years of age and 11 patients with documented exercise-induced ischemia. Resting
      and postexercise measurements were taken, and several MCG parameters were
      defined. For 19 of 29 MCG parameters, there were significant differences between
      healthy females and males (p < or = 0.05). For nine MCG parameters, there were
      differences between older and younger healthy subjects (p < 0.01). Therefore the
      age and sex of a subject should be considered when evaluating the MCG. Thirteen
      parameters separated the patients from the controls (areas under the receiver
      operating characteristic curve >80%). The repolarization stabilization interval,
      a parameter based on the time-evolution of contour maps, performed the best.
      Magnetocardiography performed in clinical settings is a potential screening tool
      for ischemia that should be further explored.

PMID- 15446506
TI  - Three-dimensional, quantitative analysis of desmin and smooth muscle alpha actin
      expression during angiogenesis.
AB  - Angiogenic therapies have been designed for many pathological conditions, but
      when used as a single therapy, the clinical results have fallen short of
      expectations. In addition, strategies for vascularizing engineered tissues have
      been unsuccessful in promoting the formation of an extensive, stable vasculature.
      Recent evidence suggests that mural cells play a critical role in the success of
      these approaches, but our current understanding of the function of mural cells in
      the microvasculature is incomplete. We studied the three-dimensional spatial and
      temporal kinetics of the mural cell markers desmin and smooth muscle alpha actin
      during angiogenesis in an in vivo fibrin gel model. The results led to the
      following conclusions: (1) desmin and smooth muscle alpha actin positive cells
      are present during the initial development of vessel sprouts; (2) the presence of
      these cells in the microvasculature is not always an indicator of vessel
      stability; and (3) the mural cell markers desmin and smooth muscle alpha actin
      exhibit differential staining patterns during vessel formation. These findings
      shed new light on the complexity of the relationship between mural cells and the
      formation of a mature, stable microcirculation.

PMID- 15446507
TI  - Quantitative dynamics of in vivo bone marrow neutrophil production and egress in
      response to injury and infection.
AB  - Production rates of blood cells from the bone marrow (BM) can be determined from
      pool size and residence time in the circulation only during steady state. We
      describe a method to evaluate changes in BM neutrophil production following
      severe injury. Male CD-1 mice underwent nonlethal cutaneous burn injury, a lethal
      burn injury with Pseudomonas aeruginosa infection, or sham treatment, and
      received bromodeoxyuridine (BrdU) to label proliferative cells. Rates of BM
      neutrophil production and release into the circulation were determined using a
      mathematical model that integrates BM neutrophil pool size and fraction of BrdU
      labeled cells as a function of time. Absolute rates could not be quantified
      without BrdU data for the neutrophil progenitor pool; however, relative rates
      could be determined. BM neutrophil production and release significantly increased
      after injury. After nonlethal burn, release transiently exceeded production,
      causing a temporary decrease in BM neutrophil stores followed by reestablishment
      of a steady-state BM neutrophil pool similar to sham controls. After lethal burn
      infection, release always exceeded production, causing complete depletion of BM
      neutrophils and suppression of BM neutrophil production. This method is generally
      applicable to estimating production rates of nonproliferating, terminally
      differentiated cells, arising from a stem cell pool in vivo.

PMID- 15446508
TI  - Oriented Schwann cell monolayers for directed neurite outgrowth.
AB  - Schwann cells are an important component of the peripheral nervous system and
      participate in peripheral nerve regeneration. They create a supportive
      environment for neurite outgrowth by releasing trophic factors and up-regulating
      permissive molecules on their surface. In addition, Schwann cells are able to
      self-organize into linear arrays in vitro and in vivo, suggesting a possible role
      in neurite guidance. Previously, we showed that Schwann cell placement and
      orientation in subconfluent cultures can be controlled using
      microlithographically patterned laminin substrates (Thompson, D. M., and H. M.
      Buettner. Tissue Eng. 7(3):247-266, 2001). In the current study, these substrates
      were used to create oriented Schwann cell monolayers. Both Schwann cell
      orientation and coverage were quantified in response to seeding density, culture
      medium, and micropattern dimensions. In serum-free medium, increasing the seeding
      density yielded a linear increase in coverage of the substrate area but decreased
      cell alignment. In an alternate approach, Schwann cells were first seeded in
      serum-free medium at moderate seeding density, allowed to align, then expanded in
      serum-containing growth medium. This produced complete coverage without large
      seeding densities while preserving alignment to the micropattern. Alignment and
      coverage were unaffected by micropattern dimensions. This work provides a useful
      methodology for investigating Schwann cell guidance effects on growing neurites.

PMID- 15446510
TI  - An improved Morris Water Maze tracking algorithm for psychophysical studies.
AB  - An algorithm to track a rat swimming in a Morris Water Maze has been developed.
      The system is automatically configured to any pool and relative suitable light
      conditions. It tracks the rat's position and head pose 10 times per second. The
      output data is displayed in a bitmap and also in a text file. The system was
      tested with an X - Y plotter using a simulated rat swimming in the maze. Known
      signals were provided to a model rat and compared to the position and pose
      information provided by the tracking algorithm. The algorithm was able to track
      rat velocities up to 2.32 m/s, localize rat position to 4 mm within the maze, and
      provide head pose information. Early prototypes of the algorithm were also used
      to track actual rats in a water maze.

PMID- 15446509
TI  - Effects of droplet velocity, diameter, and film height on heat removal during
      cryogen spray cooling.
AB  - Cryogen spray cooling (CSC) is an effective method to reduce or eliminate
      epidermal damage during laser treatment of various dermatoses. This study sought
      to determine the effects of specific cryogen properties on heat removal. Heat
      removal was quantified using an algorithm that solved an inverse heat conduction
      problem from internal temperature measurements made within a skin phantom. A
      nondimensional parameter, the Weber number, characterized the combined effects of
      droplet velocity, diameter, and surface tension. CSC experiments with laser
      irradiation were conducted on ex vivo human skin samples to assess the effect of
      Weber number on epidermal protection. An empirical relationship between heat
      removal and the difference in droplet temperature and the substrate, droplet
      velocity, and diameter was obtained. Histological sections of irradiated ex vivo
      human skin demonstrated that sprays with higher Weber numbers increased epidermal
      protection. Results indicate that the cryogen film acts as an impediment to heat
      transfer between the impinging droplets and the substrate. This study offers the
      importance of Weber number in heat removal and epidermal protection.

PMID- 15446511
TI  - Dynamics, stability, and control of stepping.
AB  - The dynamics, stability, and control of stepping are considered. The role of
      internal models is elaborated. The main objective of the paper is to provide a
      better understanding of the machinery and processing in the central nervous
      system (CNS) that relates to stepping. The role of the vestibular system in
      balance and balance recovery is described. Balance and balance recovery are
      essential in stepping, and guarantee the stability of the system before, during,
      and after stepping. In sagittal standing, humans use two distinct sets of control
      strategies to maintain their postural stability in response to external
      disturbance. In one set of strategies, the configuration of the base of support,
      namely, the position of the feet, remains unchanged. The ankle and hip strategies
      are examples of postural adjustments where the feet do not move. When the
      disturbances are large, and move the center of mass or pressure outside the
      support boundaries, stepping strategies are required. A simple control strategy
      is proposed for illustrative purposes. Its effectiveness is verified by computer
      simulation of a seven-link two-dimensional sagittal biped. The applications of
      the model in assessing trauma and injury are discussed.

PMID- 15446512
TI  - Mechanical stimulation toward tissue engineering of the knee meniscus.
AB  - Current clinical practices do not adequately regenerate the meniscus of the knee
      secondary to a tear. Complete or partial meniscus removal leads to degenerative
      changes within the joint. Tissue engineering of the meniscus promises a potent
      solution. Before embarking on tissue engineering of the meniscus, it is crucial
      to have a thorough comprehension of the biomechanical role that this tissue
      fulfills and how the structure of meniscus is uniquely suited to that purpose. To
      better understand this, we have examined the meniscus, as well as associated
      tissues, within the body. For the first time, the knee meniscus is rigorously
      compared to ligament, tendon, and cartilage, and inferences are drawn on how
      mechanical stimulation may be used to channel growth in the meniscus. We have
      examined in detail the loading conditions that these tissues experience in vivo
      and how each is uniquely adapted to its loading environment. These tissues are
      capable of achieving some degree of remodeling because of mechanical stimuli. By
      understanding the mechanisms that can stimulate and promote regeneration in
      related tissues, we hope to harness that knowledge to achieve the goal of
      meniscal regeneration.

PMID- 15446513
TI  - Changing ethical standards in scientific publication.

PMID- 15446514
TI  - Dysfunction of the tendon of tibialis posterior.

PMID- 15446515
TI  - A flexible intramedullary nails for fractures in children.

PMID- 15446516
TI  - Stable elastic intramedullary nailing for fractures of the femur in children.
AB  - Fractures of the femur are the most incapacitating fractures in children.
      Conservative treatment necessitates a long stay in hospital for traction and
      subsequent immobilisation in an uncomfortable cast. This treatment is not well
      tolerated, especially in adolescents. Moreover, near the end of growth, accurate
      reduction is necessary, as malunion is no longer correctable by growth. Stable
      elastic intramedullary nailing uses two flexible nails which are introduced
      percutaneously either through the lower metaphysis or the subtrochanteric area.
      This technique does not disturb the healing of the fracture. The elasticity of
      the device allows slight movement at the fracture site which favours union.
      Reduction and stabilisation are adequate and the operative risk is very low. A
      cast is not required, functional recovery is rapid and the patient is allowed to
      walk with crutches after seven to ten days according to the type of fracture.
      This technique is very efficient in adolescents and can be used after the age of
      seven years when conservative treatment is unsuccessful.

PMID- 15446517
TI  - Orthopaedic surgeons and fragility fractures. A survey by the Bone and Joint
      Decade and the International Osteoporosis Foundation.

PMID- 15446518
TI  - Allograft bone in two-stage revision of the hip for infection. Is it safe?
AB  - A two-stage procedure was carried out on 57 patients with confirmed infection in
      a hip replacement. Allograft bone was used in the second stage. Pathogenic
      organisms were identified in all patients. In stage 1, the prosthesis was removed
      together with infected tissue. Antibiotics were added to customised cement beads.
      Systemic antibiotics were not used. At the second stage, 45 of the patients had
      either acetabular impaction grafting, femoral impaction grafting or a
      combination; 12 had a massive allograft. Eight patients suffered recurrent
      infection (14%), in six with the original infecting organism. The risk factors
      for re-infection were multiple previous procedures and highly resistant
      organisms. We believe that systemic antibiotic therapy should be considered for
      these patients. Allograft bone is shown to be a useful adjunct in most infected
      hip replacements with considerable loss of bone stock.

PMID- 15446519
TI  - L-shaped caliper for limb length measurement during total hip arthroplasty.
AB  - The existing methods of assessing limb lengthening during total hip arthroplasty
      (THA) are prone to error because the measurements are not parallel to the limb
      lengthening axis. In order to address this, we designed a caliper to estimate
      limb lengthening during THA and evaluated its accuracy compared with our previous
      device, the straight caliper. Limb lengths were measured in 100 patients. The L
      shaped caliper was used in 50 cases and the straight caliper in 50. The
      correlation between intra-operative and post-operative radiographic measurements
      was significantly improved using the L-shaped device (p < 0.0001, r = 0.934).
      This method was extremely accurate in predicting changes in limb length due to
      surgery.

PMID- 15446520
TI  - Pre-operative predictors of the requirement for blood transfusion following total
      hip replacement.
AB  - We have reviewed prospective data on 1016 patients who underwent unilateral total
      hip replacement to establish the pre-operative risk factors associated with peri
      operative blood transfusion. Most patients who required transfusion were older
      and were of lower weight, height, pre-operative haemoglobin level and body mass
      index than patients who were not transfused. Multivariate analysis revealed that
      only the pre-operative haemoglobin level and the patients weight were identified
      as significant independent factors increasing the need for transfusion (p <
      0.001). A haemoglobin level below 12 g/dl was associated with a threefold
      increase in transfusion requirement.

PMID- 15446521
TI  - Corrosion of cemented titanium femoral stems.
AB  - Cemented titanium stems in hip arthroplasty are associated with proximal cement
      stem ebonding and early failure. This was well publicised with the 3M Capital
      hip. However, corrosion in this setting has been reported with only one stem
      design and is less widely accepted. We present a series of 12 cemented titanium
      Furlong Straight Stems which required revision at a mean of 78 months for thigh
      pain. At revision the stems were severely corroded in a pattern which was typical
      of crevice corrosion. Symptoms were eliminated after revision to an all-stainless
      steel femoral prosthesis of the same design. We discuss the likely causes for the
      corrosion. The combination of a titanium stem and cement appears to facilitate
      crevice corrosion.

PMID- 15446522
TI  - Patient preferences in knee prostheses.
AB  - A total of 344 patients underwent bilateral total knee replacement (TKR) using a
      different prosthesis on each side. Four knee prostheses were used: anterior and
      posterior cruciate-retaining (ACL-PCL), posterior cruciate-retaining (PCL),
      medial or lateral pivot (MLP), and posterior cruciate-substituting (PS). All
      patients had good or excellent results. The range of movement, relief from pain,
      alignment, and stability did not vary among any of the prostheses. Forty-one of
      46 patients (89%) preferred the ACL-PCL to the PS knee and 27 of 35 patients
      (77%) the MLP knee to the PS knee. Of the patients with an ACL-PCL knee on one
      side and a MLP on the other, an equal number preferred each type. The MLP knee
      was preferred to the PCL by 34 (79%) patients. PS and PCL knees were preferred
      equally. Patients with bilateral TKRs preferred retention of both their cruciate
      ligaments or substitution with a medial or lateral pivot prosthesis.

PMID- 15446523
TI  - Unicompartmental knee arthroplasty. 2- to 12-year results in a community
      hospital.
AB  - We report the outcome of 135 knees with anteromedial osteoarthritis in which the
      Oxford meniscal-bearing unicompartmental arthroplasty was inserted in a district
      general hospital by a single surgeon. All the knees had an intact anterior
      cruciate ligament, a correctable varus deformity and the lateral compartment was
      uninvolved or had only minor osteoarthritis. The mean follow-up was 5.82 years (2
      to 12). Using revision as the end-point, the outcome for every knee was
      established. Five knees have been revised giving a cumulative rate of survival of
      the prosthesis at ten years of 94.04% (95% confidence interval 84.0 to 97.8).
      Knee rating and patient function were assessed using the modified Knee Society
      scoring system. The mean knee score was 92.2 (51 to 100) and the mean functional
      score 76.2 (51 to 100). The survival of the implant is comparable to that
      reported by the designers of the prosthesis and not significantly different from
      that for total knee replacement. Unicompartmental knee replacement offers a
      viable alternative in patients with medial osteoarthritis. Appropriate selection
      of patients and good surgical technique are the key factors.

PMID- 15446524
TI  - Retrieval of a well-functioning extensor mechanism allograft from a total knee
      arthroplasty. Clinical and histological findings.
AB  - We present the histological findings of an extensor mechanism allograft which was
      used in a total knee arthroplasty two years after implantation. Analysis of the
      graft was undertaken at four distinct anatomical levels and it was found to be
      incorporated into host tissue at each level. A wedge of fibrinoid necrosis,
      probably related to impingement of the graft on the tibial polyethylene insert,
      was seen. Impingement may play a role in the injury and necrosis of an allograft
      and may be one mode of failure in an extensor mechanism allograft.

PMID- 15446525
TI  - Osteochondral autologous transplantation for the treatment of full-thickness
      articular cartilage defects of the shoulder.
AB  - We performed eight osteochondral autologous transplantations from the knee joint
      to the shoulder. All patients (six men, two women; mean age 43.1 years) were
      documented prospectively. In each patient the stage of the osteochondral lesion
      was Outerbridge grade IV with a mean size of the affected area of 150 mm2. All
      patients were assessed by using the Constant score for the shoulder and the
      Lysholm score for the knee. Standard radiographs, magnetic resonance imaging and
      second-look arthroscopy were used to assess the presence of glenohumeral
      osteoarthritis and the integrity of the grafts. After a mean of 32.6 months (8 to
      47), the mean Constant score increased significantly. Magnetic resonance imaging
      revealed good osseointegration of the osteochondral plugs and congruent articular
      cartilage at the transplantation site in all but one patient. Second-look
      arthroscopy performed in two cases revealed a macroscopically good integration of
      the autograft with an intact articular surface. Osteochondral autologous
      transplantation in the shoulder appears to offer good clinical results for
      treating full-thickness osteochondral lesions of the glenohumeral joint. However,
      our study suggests that the development of osteoarthritis and the progression of
      pre-existing osteoarthritic changes cannot be altered by this technique.

PMID- 15446526
TI  - Anterior submuscular transposition of the ulnar nerve. For post-operative focal
      neuropathy at the elbow.
AB  - Outcome studies of revision surgical treatment for recurrent or persistent
      neuropathy of the ulnar nerve at the elbow are relatively rare and none involves
      patient self-assessment. In this study of 40 patients (41 elbows), a clear
      discrepancy is shown between clinical assessment and the patient's own view. From
      clinical assessment, 20% of patients had an excellent result, whereas only one
      (2.5%) patient self-reported a complete cure. More reports using patient self
      assessment and validated scores are required.

PMID- 15446527
TI  - Seventeen-year survivorship analysis of silastic metacarpophalangeal joint
      replacement .
AB  - We reviewed the records and radiographs of 381 patients with rheumatoid arthritis
      who had undergone silastic metacarpophalangeal joint replacement during the past
      17 years. The number of implants was 1336 in the course of 404 operations.
      Implant failure was defined as either revision or fracture of the implant as seen
      on radiography. At 17 years, the survivorship was 63%, although on radiographs
      two-thirds of the implants were seen to be broken. Factors which improved
      survival included soft-tissue balancing, crossed intrinsic transfer and
      realignment of the wrist. Surgery to the thumb and proximal interphalangeal joint
      had a deleterious effect and the use of grommets did not protect the implant from
      fracture.

PMID- 15446528
TI  - Vascularised bone graft from the base of the second metacarpal for refractory
      nonunion of the scaphoid.
AB  - A vascularised bone-graft procedure from the base of the second metacarpal was
      performed in 14 patients with nonunion of the scaphoid. There were 11 men and
      three women with a mean age of 22 years. In eight patients, who had dorsiflexed
      intercalated segment instability (DISI), an open wedge was formed at the site of
      nonunion, and the vascular pedicle was grafted from the volar side. In the six
      patients without DISI, transplantation was carried out through the same dorsal
      skin incision. Complete bony union was obtained in all patients after a mean post
      operative period of 10.2 weeks, and DISI was corrected in all affected patients.
      According to Cooney's clinical scoring system, the results were excellent in
      five, good in six, and fair in three patients. Because of its technical
      simplicity and the limited dissection needed, the procedure should be considered
      for the primary surgical treatment of patients with nonunion of the scaphoid.

PMID- 15446529
TI  - Multiple congenital brachymetatarsia. A one-stage combined shortening and
      lengthening procedure without iliac bone graft.
AB  - We performed nine metatarsal and three proximal phalangeal lengthenings in five
      patients with congenital brachymetatarsia of the first and one or two other
      metatarsal bones, by a one-stage combined shortening and lengthening procedure
      using intercalcary autogenous bone grafts from adjacent shortened metatarsal
      bones. Instead of the isolated lengthening of the first and the other metatarsal
      bones, we shortened the adjacent normal metatarsal and used the excised bone to
      lengthen the short toes, except for the great toe, to restore the normal
      parabola. One skin incision was used. All the operations were performed
      bilaterally and the patients were followed up for a mean period of 69.5 months
      (29 to 107). They all regained a nearly normal parabola and were satisfied with
      the cosmetic results. Our technique is straightforward and produces good cosmetic
      results. Satisfactory, bony union is achieved, morbidity is low, and no
      additional surgery is required for the removal of metal implants.

PMID- 15446530
TI  - Chevron osteotomy in hallux valgus. Ten-year results of 112 cases.
AB  - The Chevron osteotomy was described in 1976. There have, however, been only short
      to mid-term follow-up reviews, often with small numbers of patients. We looked
      at 112 feet (73 patients) with a minimum follow-up of ten years following Chevron
      osteotomy with a distal soft-tissue procedure. Clinical evaluation was calculated
      using the hallux score of the American Orthopedic Foot and Ankle Society (AOFAS).
      For 47 feet (30 patients), the results were compared with those from an interim
      follow-up of 5.6 years. The AOFAS-score improved from a pre-operative mean of
      46.5 points to a mean of 88.8 points after a mean of 12.7 years. The first
      metatarsophalangeal (MTP) angle showed a mean pre-operative value of 27.6 degrees
      and was improved to 14.0 degrees. The first intermetatarsal (IM) angle improved
      from a pre-operative mean value of 13.8 degrees to 8.7 degrees. The mean pre
      operative grade of sesamoid subluxation was 1.7 on a scale from 0 to 3 and
      improved to 1.2. Measured on a scale from 0 to 3, arthritis of the first MTP
      joint progressed from a mean of 0.8 to 1.7. Comparing the results in patients
      younger and older than 50 years, the Chevron osteotomy performed equally in both
      age groups. Analysing the subgroup of 47 feet with a post-operative follow-up of
      both 5.6 and 12.7 years, the AOFAS pain and the overall score showed a further
      improvement between both follow-up evaluations. The MTP angle, first IM angle and
      sesamoid position remained unchanged. The progression of arthritis of the first
      MTP joint between 5.6 and 12.7 years post-operatively was statistically
      significant. Only one patient required a revision procedure due to painful
      recurrence of the deformity. Excellent clinical results following Chevron
      osteotomy not only proved to be consistent, but showed further improvement over a
      longer follow-up period. The mean radiographic angles were constant without
      recurrence of the deformity. So far, the statistically significant progression of
      first MTP joint arthritis has not affected the clinical result, but this needs
      further observation.

PMID- 15446531
TI  - The association of lumbar spondylolisthesis with collagen IX tryptophan alleles.
AB  - Two collagen type IX gene polymorphisms that introduce a tryptophan residue into
      the protein's triple-helical domain have been linked to an increased risk of
      lumbar disc disease. To determine whether a particular subset of symptomatic
      lumbar disease is specifically associated with these polymorphisms, we performed
      a prospective case-control study of 107 patients who underwent surgery of the
      lumbar spine. Patients were assigned to one of five clinical categories
      (fracture, disc degeneration, disc herniation, spinal stenosis without
      spondylolisthesis and spinal stenosis with spondylolisthesis) based on history,
      imaging results, and findings during surgery. Of the 11 tryptophan-positive
      patients, eight had spinal stenosis with spondylolisthesis and three had disc
      herniation. The presence of the tryptophan allele was significantly associated
      with African-American or Asian designation for race (odds ratio 4.61, 95% CI 0.63
      to 25.35) and with the diagnosis of spinal stenosis with spondylolisthesis (odds
      ratio 6.81, 95% CI 1.47 to 41.95). Our findings indicate that tryptophan
      polymorphisms predispose carriers to the development of symptomatic spinal
      stenosis associated with spondylolisthesis which requires surgery.

PMID- 15446532
TI  - Extrapleural anterolateral decompression in tuberculosis of the dorsal spine.
AB  - We reviewed 64 anterolateral decompressions performed on 63 patients with
      tuberculosis of the dorsal spine (D1 to L1). The mean age of the patients was 35
      years (9 to 73) with no gender preponderance. All patients had severe paraplegia
      (two cases grade III, 61 cases grade IV). The mean number of vertebral bodies
      affected was 2.6; the mean pre-treatment kyphosis was 24.8 degrees (7 to 84). An
      average of 2.9 ribs were removed in the course of 64 procedures. The mean time
      taken at surgery was 2.45 hours when two ribs were removed and 3.15 hours when
      three ribs were removed. Twelve patients (19%) showed signs of neurological
      recovery within seven days, 33 patients (52%) within one month and 12 patients
      (19%) after two months; but six patients (10%) showed no neurological recovery.
      Forty patients were followed up for more than two years. In 34 (85%) of these
      patients there was no significant change in the kyphotic deformity; two patients
      (5%) showed an increase of more than 20 degrees.

PMID- 15446533
TI  - Long-term disability after neck injury. a comparative study.
AB  - Claims for personal injury after whiplash injury cost the economy of the United
      Kingdom more than pound 3 billion per year, yet only very few patients have
      radiologically demonstrable pathology. Those sustaining fractures of the cervical
      spine have been subjected to greater force and may reasonably be expected to have
      worse symptoms than those with whiplash injuries. Using the neck disability index
      as the outcome measure, we compared pain and functional disability in four groups
      of patients who had suffered injury to the cervical spine. After a mean follow-up
      of 3.5 years, patients who had sustained fractures of the cervical spine had
      significantly lower levels of pain and disability than those who had received
      whiplash injuries and were pursuing compensation (p < 0.01), but had similar
      levels to those whiplash sufferers who had settled litigation or had never sought
      compensation. Functional recovery after neck injury was unrelated to the physical
      insult. The increased morbidity in whiplash patients is likely to be
      psychological and is associated with litigation.

PMID- 15446534
TI  - Delayed internal fixation of fractures of the neck of the femur in young adults.
      A prospective, randomised study comparing closed and open reduction.
AB  - We have compared the results and complications after closed and open reduction
      with ternal fixation in young adults with displaced intracapsular fractures
      (Garden grades III and IV) of the neck of the femur. We also studied the risk
      factors which influenced nonunion and the development of avascular necrosis
      (AVN). A total of 102 patients aged between 15 and 50 years was randomised to
      receive either closed or open reduction. Both groups were compared for age,
      gender, time to surgery and posterior comminution as well as for union and
      complications. Using univariate and multivariate analysis the factors influencing
      nonunion and AVN were assessed. Of the 102 patients, 92 were available for
      review. There was no significant difference between the groups in terms of union
      (p = 0.93) and AVN at two years (p = 0.85). Posterior comminution, poor reduction
      and improper placement of the screws were the major factors contributing to
      nonunion. The overall incidence of AVN was 16.3% (15 of 92 patients) and it was
      not influenced by these factors. A delay of more than 48 hours before surgery did
      not influence the rate of union or the development of AVN when compared with
      operation within 48 hours of injury.

PMID- 15446535
TI  - Severity of disease and risk of malignant change in hereditary multiple
      exostoses. A genotype-phenotype study.
AB  - We performed a prospective genotype-phenotype study using molecular screening and
      clinical assessment to compare the severity of disease and the risk of sarcoma in
      172 individuals (78 families) with hereditary multiple exostoses. We calculated
      the severity of disease including stature, number of exostoses, number of
      surgical procedures that were necessary, deformity and functional parameters and
      used molecular techniques to identify the genetic mutations in affected
      individuals. Each arm of the genotype-phenotype study was blind to the outcome of
      the other. Mutations EXT1 and EXT2 were almost equally common, and were
      identified in 83% of individuals. Non-parametric statistical tests were used.
      There was a wide variation in the severity of disease. Children under ten years
      of age had fewer exostoses, consistent with the known age-related penetrance of
      this condition. The severity of the disease did not differ significantly with
      gender and was very variable within any given family. The sites of mutation
      affected the severity of disease with patients with EXT1 mutations having a
      significantly worse condition than those with EXT2 mutations in three of five
      parameters of severity (stature, deformity and functional parameters). A single
      sarcoma developed in an EXT2 mutation carrier, compared with seven in EXT1
      mutation carriers. There was no evidence that sarcomas arose more commonly in
      families in whom the disease was more severe. The sarcoma risk in EXT1 carriers
      is similar to the risk of breast cancer in an older population subjected to
      breast-screening, suggesting that a role for regular screening in patients with
      hereditary multiple exostoses is justifiable.

PMID- 15446536
TI  - Measurement of bowing of the radius.
AB  - Fractures and plastic deformities of the forearm are common in children. While
      axial deformities are easily recognised and treated, bowing of the radius may be
      overlooked. Physiological bowing is essential for full rotation of the forearm.
      We have used the method of Schemitsch and Richards to estimate the degree of
      bowing in 100 children who had not suffered a fracture of the forearm. The site
      of maximum bowing remained constant at 60.39% of the length of the radius (95% CI
      59.65 to 61.14). The value of maximum bowing did not exceed 10% of the total
      length (mean value 7.21%; 95% CI 7.00 to 7.41). This study provides information
      that can be useful for the diagnosis of bowing and for the evaluation of post
      traumatic deformities.

PMID- 15446537
TI  - Dislocations of the elbow in children.
AB  - A total of 33 children were treated for acute traumatic dislocation of the elbow
      between 1994 and 2002; 30 dislocations were posterior and three anterior. Eight
      children had a pure dislocation and 25 had an associated fracture of the elbow.
      Two had compound injuries. Two children had injury to the ulnar nerve, one to the
      radial nerve and one to the median nerve together with injury to the brachial
      artery. Twenty required open reduction. Complications included pseudarthrosis of
      the medial epicondyle in one child and loss of flexion and rotation of between 10
      degrees and 30 degrees in ten others. Meticulous clinical and radiological
      assessment is mandatory in children with dislocation of the elbow to exclude
      associated injuries. The results were excellent to good in 22 patients, fair in
      ten and poor in one.

PMID- 15446538
TI  - Monitoring of the sciatic nerve during hamstring lengthening by evoked EMG.
AB  - Traction injury to the sciatic nerve can occur during hamstring lengthening. The
      aim of this study was to monitor the influence of hamstring lengthening on
      conduction in the sciatic nerve using evoked electromyography (EMG). Ten children
      with spastic cerebral palsy underwent bilateral distal hamstring lengthening.
      Before lengthening, the evoked potential was recorded with the patient prone.
      During lengthening, it was recorded with the knee flexed to 90 degrees, 60
      degrees and 30 degrees, and at the end of lengthening with the hip and knee
      extended. In all patients, the amplitude of the evoked EMG gradually decreased
      with increasing lengthening. The mean decrease with the knee flexed to 60 degrees
      was 34% (10 to 77), and to 30 degrees, 86% (52 to 98) compared with the pre
      lengthening amplitude. On hip extension at the end of the lengthening procedure,
      the EMG returned to the pre-lengthening level. Monitoring of the evoked EMG
      potential of the sciatic nerve during and after hamstring lengthening, may be
      helpful in preventing traction injury.

PMID- 15446539
TI  - Interspinous bursitis in an athlete.
AB  - We present a case of L2/3 interspinous bursitis treated with extraspinal
      injections. No previous investigations have used fluoroscopically guided spinal
      injections to confirm the clinical relevance of the MRI features of this type of
      bursae. Autopsy studies have revealed an increased incidence of interspinous
      lumbar bursal cavities with advancing age. Afflicted patients present with
      localised, midline lower lumbar pain exacerbated by extension. In young athletes
      these symptoms can mimic spondylolysis. MRI is useful in detecting soft-tissue
      injury of the posterior elements. Fluoroscopically guided diagnostic and
      therapeutic extraspinal injections can be used for confirmation and treatment of
      pain from such bursae.

PMID- 15446540
TI  - A correction of windswept deformity by fixator assisted nailing. A report of two
      cases.
AB  - We report two cases with windswept deformities of the lower extremities. All
      deformities were corrected by fixator-assisted intramedullary nailing. At the
      latest follow-up, the patients had normal alignment, without symptoms and no loss
      of correction.

PMID- 15446541
TI  - A spontaneous compartment syndrome in a patient with diabetes.
AB  - A compartment syndrome is an orthopaedic emergency which can result from a
      variety of causes, the most common being trauma. Rarely, it can develop
      spontaneously and several aetiologies for spontaneous compartment syndrome have
      been described. We describe a patient with diabetes who developed a spontaneous
      compartment syndrome. The diagnosis was delayed because of the atypical
      presentation.

PMID- 15446542
TI  - Augmentation of tendon-bone healing by the use of calcium-phosphate cement.
AB  - The healing of a hamstring graft to bone is the weak link in the reconstruction
      of a cruciate ligament using this donor material. We therefore investigated the
      augmentation of healing at the tendon-bone interface using calcium-phosphate
      cement (CPC). We performed semitendinosus autograft reconstructions of the
      anterior cruciate ligament on both knees of 22 New Zealand white rabbits. The
      interface between the grafted tendon and the bone tunnel for one knee was filled
      with CPC. Six rabbits were killed at the end of the first and second post
      operative weeks in order to evaluate the biomechanical changes. Two rabbits were
      then killed sequentially at the end of weeks 1, 3, 6, 12 and 24 after operation
      and tissue removed for serial histological observation. Histological examination
      showed that the use of CPC produced early, diffuse and massive bone ingrowth. By
      contrast, in the non-CPC group of rabbits only a thin layer of new bone was seen.
      Mechanical pull-out testing at one week showed that the mean maximal tensile
      strength was 6.505 +/- 1.333 N for the CPC group and 2.048 +/- 0.950 N for the
      non-CPC group. At two weeks the values were 11.491 +/- 2.865 N and 5.452 +/-
      3.955 N, respectively. Our findings indicate that CPC is a potentially promising
      material in clinical practice as regards its ability to reinforce the fixation of
      the tendon attachment to bone and to augment the overall effectiveness of tendon
      healing to bone.

PMID- 15446543
TI  - Regional regenerative potential of meniscal cartilage exposed to recombinant
      insulin-like growth factor-I in vitro.
AB  - It is well recognised that meniscal tears situated within the inner, avascular
      region do not heal. We investigated the potential effect of insulin-like growth
      factor-I (IGF-I) in promoting regeneration of meniscal tissue in the inner,
      middle and outer zones of the meniscus. Sheep menisci were harvested and
      monolayer cell cultures prepared. Various concentrations of IGF-I were used in
      the presence or absence of 10% fetal calf serum (FCS). We measured the uptake of
      radioactive thymidine, sulphur, and proline to assess cell proliferation and
      formation of extracellular matrix (ECM). IGF-I, in the presence or absence of
      FCS, increased the formation of DNA and ECM in all meniscal zones. However, the
      response of the cells from the avascular zone was greater than that from the
      vascular zone. Our findings indicate that fibrochondrocytes cultured from
      avascular meniscal tissue have the ability to regenerate when exposed to anabolic
      cytokines such as IGF-I.

PMID- 15446544
TI  - Expression of vascular endothelial growth factor during healing of the meniscus
      in a rabbit model.
AB  - Our aim was to investigate vascular endothelial growth factor (VEGF) expression
      after lacerations of a meniscus in a rabbit model. Specimens of meniscus were
      examined using immunohistochemistry, enzyme-linked immunoassay and the reverse
      transcription polymerase chain reaction after one, two, five or ten weeks. In the
      periphery of the meniscus 90% of the lacerations had healed after five and ten
      weeks, but no healing was observed in the avascular area. Expression of VEGF
      protein and VEGF mRNA was found in the meniscus of both the operated and the
      contralateral sites but both were absent in control rabbits which had not
      undergone operation. The highest expression of VEGF was found in the avascular
      area after one week (p < 0.001). It then lessened at both the vascular and
      avascular areas, but still remained greater in comparison with the control
      meniscus (p < 0.05). Despite greater expression of VEGF, angiogenesis failed at
      the inner portion. These findings demonstrated the poor healing response in the
      avascular area which may not be caused by an intrinsic cellular insufficiency to
      stimulate angiogenesis.

PMID- 15446545
TI  - Dupuytren's disease.

PMID- 15446546
TI  - Failure of an uncemented non-porous metal-backed prosthesis with augmentation
      using impacted allograft for acetabular revision.

PMID- 15446547
TI  - Spontaneous tendon ruptures in alkaptonuria.

PMID- 15446548
TI  - [Tumor suppressor gene p53 and molecular targeting therapy].
AB  - p53 is a molecule which is activated upon a DNA stress, such as gamma
      irradiation, UV, hypoxia, virus infection, and DNA damage, leading protection of
      cells by inducing target genes. The molecules activated by p53 induce apoptosis,
      cell cycle arrest, and DNA repair to conserve genome. In order to kill cancer
      cells, many strategies targeting p53 have been reported. Preclinical studies have
      demonstrated that overexpression of wt-p53 by adenovirus vector is capable of
      inducing apoptosis in cancers. Furthermore, restoration of mt-p53 into wild type
      by compound has been under development. In this review, clinical application of
      molecular targeting therapy for p53 is discussed.

PMID- 15446549
TI  - [Surgical treatment for bone and soft tissue sarcoma].
AB  - There are many kinds of wide excision or wide resection, which are methods to
      remove the tumor with surrounding tissues. The curability of wide resection
      depends on the range and characteristics of the normal surrounding tissues. The
      fascia, periosteum and perivascular sheath act as barriers against invasion of
      tumors. Therefore, evaluation of the surgical margin is essential in surgery for
      malignancy. Some sarcomas characteristically show invasive growth patterns while
      others have a discrete border. Causes of the local recurrence are 1) insufficient
      surgical margin, 2) skip metastasis, 3) tumor thrombus, and 4) lymph node
      metastasis. The so-called "Safety surgical margin" is the margin that prevents
      local recurrence due to insufficient surgical treatment. Local recurrence due to
      other causes can not be treated by surgery alone as chemotherapy is also
      required. For example, the infiltrative type of malignant fibrous histiocytoma
      requires a curative procedure. On the other hand, non-infiltrative types of
      sarcoma or high-grade sarcoma, which are good responders to preoperative
      treatment, are locally controlled by an adequate wide margin procedure. When the
      tumor is close to the bone, main vessels and/or nerves, it is sometimes very
      difficult to preoperatively decide whether or not to sacrifice these important
      organs. A new surgical method, "In Situ Preparation (ISP)," is a useful method to
      solve such problems. ISP makes it possible to evaluate the surgical margin
      without contamination. And additional procedures including alcohol soaking or
      pasteurization can be achieved according to the surgical margin. Because ISP can
      prevent overtreatment, the number of our cases that require resection of the
      nerves or vessels have decreased. After a wide resection, there have been many
      possible complications, including infection, deep venous thrombosis, loosening of
      prosthesis, skin necrosis, and arterial occlusion. Once postoperative
      complications occur, patients must remain in the hospital for a long time. To
      prevent this, the preservation of normal tissue, meaning reduction of surgical
      margin, is important.

PMID- 15446550
TI  - [Pulmonary metastasectomy for osteosarcomas and soft tissue sarcomas].
AB  - To evaluate the efficacy of aggressive pulmonary metastasectomy for treating
      osteosarcomas and soft tissue sarcomas, we reviewed 105 cases treated in our
      hospital between 1990 and 2002. There were 57 males and 48 females, 44
      osteosarcomas (OS), 21 synovial sarcomas (Syno), 16 malignant fibrous
      histiocytomas (MFH), 4 leiomyosarcomas (Leio), 4 alveolar soft part sarcomas
      (ASPS) and 16 others (including chondrosarcoma and liposarcoma). A total of 904
      metastases were resected (8.6(0-49)/patients) and 244 thoracotomies
      (2.3/patients) were performed. Mean number of initial metastasectomies was 3.7 (0
      26), disease-free interval (DFI) was 13. 8 months (0-96), and mean diameter of
      maximum resected metastases for one patient was 20.4 (5-90) mm. Five-and 10-year
      survival rates of all cases were 44.9% and 32.0% respectively. Those of OS were
      45.8% and 38.5%, and those of soft tissue sarcomas were 44.2% and 25.5%,
      respectively. The highest 5-and 10-year survival rates among soft tissue sarcomas
      was attained in ASPS and Leio (75%), and others (51.6% and 38.7%), followed by
      Syno (42.9% and 12.4%). Long-term survival was not attained in MFH (30.9%: 5
      years). Analysis of histological types of the tumors and numbers of resected
      pulmonary metastases showed that the largest number of metastases were resected
      in ASPS (16/case) and Syno (13.8/case), followed by OS (9.0/case). MFH had the
      largest (27.1 mm) mean diameter of maximum resected metastases, followed by Leio
      (27.0 mm). Analysis of prognostic factors indicated that curativity was the most
      important prognostic factor: curative cases 42.2% (10-year survival) vs
      noncurative cases 4.2% (6-year survival). Number of resected metastases and mean
      diameter of maximum tumor size also affected the patient survival.

PMID- 15446551
TI  - [Soft tissue sarcoma: postoperative chemotherapy].
AB  - In high-grade musculoskeletal sarcomas, adjuvant chemotherapy is often performed
      to prevent distant metastases. The efficacy of chemotherapy varies according to
      the histological type of sarcoma. Prognoses are poor in patients with
      osteosarcoma, Ewing's sarcoma, or rhabdomyosarcoma, when surgery alone is
      performed. However, because these sarcomas are chemosensitive, their prognoses
      are improved with adjuvant chemotherapy. On the other hand, the efficacy of
      chemotherapy is not statistically demonstrated in non-round cell sarcomas, e. g.,
      malignant fibrous histiocytoma. Nowadays, several kinds of antitumor agents are
      usually used for adjuvant chemotherapy, and many authors have reported various
      kinds of regimens and their clinical results. Commonly used drugs include
      adriamycin, ifosfamide, cisplatin, methotrexate, cyclophosphamide, dacarbazine,
      vincristine, and actinomycin-D. Recently, high-dose chemotherapy combined with
      autologous peripheral blood or bone marrow stem cell transplantation has been
      begun in patients who do not respond to standard chemotherapy, and a better
      prognosis is expected.

PMID- 15446552
TI  - [Current strategy of chemotherapy for reflactory bone and soft tissue sarcomas].
AB  - Pulmonary metastases have been curative in some patients of osteosarcoma with
      aggressive surgical excision and intensive chemotherapy. But several
      retrospective studies and randomized II studies did not prove survival advantages
      of advanced cases with bone and soft tissue sarcoma. In treatment for refractory
      and advanced osteosarcoma after conventional treatments, clinical phase II trials
      showed 20-30% response ratio of high-dose ifosfamide and etoposide combination or
      carboplatin combination. In soft tissue sarcomas, high-dose ifosfamide and
      doxorubicin have over 50% response rate to advanced soft tissue sarcoma and total
      surgical excision of residual lung metastases prolong the survival. But new drugs
      active to refractory sarcoma had not reported in a recent decade.

PMID- 15446553
TI  - [Pathological evaluation of soft tissue sarcoma for diagnosis, prognosis and
      treatment].
AB  - Soft tissue sarcomas (STS) are rare and heterogeneous group of tumors which
      differ widely in their clinicopathological features, and have a wide spectrum of
      clinical course, ranging from indolent tumors with a good prognosis to highly
      aggressive tumors with a poor prognosis. The diagnostic process of STS is complex
      and may necessitate an array of ancillary studies, including
      immunohistochemistry, electron microscopy and molecular genetic methods. Although
      an ongoing and improved histopathological definition of individual tumor types
      has been established, there still remains a subset of mesenchymal tumors which
      are currently not readily classifiable. This review summarizes our experience and
      that of others in the approach to the pathological evaluation of STS, and
      especially emphasizes the need to use emerging molecular techniques that can
      provide important clues for diagnosis, prognosis, and treatment of STS.

PMID- 15446554
TI  - [The association of expression and gene polymorphism of the thymidylate synthase
      gene with 5-fluoro-5'-deoxyuridine sensitivity in gastric cancer cell lines].
AB  - Thymidylate synthase (TS) is a target enzyme of 5-fluorouracil (5-FU), and the TS
      expression level of cancer tissues is a potential predictor of the response to 5
      FU-based chemotherapy. The TS gene has a polymorphic tandem-repeat sequence,
      which is associated with its protein expression. Therefore, the TS polymorphism
      may also be a predictor of the response to 5-FU-based chemotherapy. In this
      study, we analyzed the TS genotype, TS protein level, and sensitivity to 5-fluoro
      5'-deoxyuridine (5'-dFUrd) in 10 human gastric cancer cell lines. TS genotype was
      classified into 2R-homozygote (2R/2R, n=3), 3R-homozygote (3R/3R, n=5), and 2R/3R
      heterozygote (2R/3R, n=2). The cell lines with 3R/3R showed a significantly
      higher IC50 value compared to those with 2R/2R or 2R/3R genotype. There was no
      relationship between TS protein level and 5'-dFUrd sensitivity. However, a
      statistically significant relationship was revealed between them when the
      subgroup with the genotypes of 2R/2R or 2R/3R was considered (r=0.815, p<0.05).
      In this subgroup, the cell lines with higher TS protein showed higher IC50 value
      for 5'-dFUrd, indicating less sensitivity to 5'-dFUrd. An identical relationship
      between the TS protein level and IC50 was also observed in the subgroup with
      3R/3R genotype, although it did not reach statistical significance (r=0.745,
      p=0.09). These results suggest that the TS gene polymorphism and TS protein level
      may be independent predictors for 5-FU-based chemotherapy.

PMID- 15446555
TI  - [Effects of radiation therapy for paraaortic lymph node involvement and recurrent
      lymph node metastases from gastric cancer].
AB  - Effects of radiation therapy for lymph node metastases from gastric cancer were
      retrospectively analyzed. The radiation sites were residual paraaortic lymph node
      involvement and postoperative recurrent lymph node metastases in 10 patients. The
      size of lymph node swelling was decreased in 6 (60%) patients after radiation
      therapy using liniac. Complaints due to lymph node metastases such as pain and
      edema of extremities were voiced by 7 patients. These complaints were eventually
      relieved or disappeared in all 7 patients. There were no severe adverse effects
      during radiation therapy, and 7 patients (70%) could shift to home care. One-year
      and 3-year survival rates were 20 and 10%, respectively. Radiation therapy for
      lymph node metastases from gastric cancer was chiefly effective in relieving
      complaints. Although it is unclear whether radiation therapy can improve the
      survival rate, these results suggest that radiation therapy could be one of the
      most useful locoregional therapies for paraaortic lymph node involvement and
      recurrent lymph node metastases from gastric cancer.

PMID- 15446556
TI  - [Prognosis and efficacy of postoperative adjuvant chemotherapy in colorectal
      cancer correlates with nucleic acid metabolizing enzymes].
AB  - We assessed the correlation among immunohistologically-stained nucleic acid
      metabolizing enzymes, such as thymidine phosphorylase (TP), thymidilate synthase
      (TS) and dehydropyrimidine dehydrogenase (DPD) detected in colorectal cancer
      patients, and the clinicopathologic factors, prognosis and efficacy of
      postoperative adjuvant chemotherapy. Results showed that TP staining positive
      cases had a higher incidence of vascular invasion and progression, and those with
      TS staining accounted for 30%. These cases also had lower 5-year survival rates.
      TS staining of 40% and DPD positive cases did not correlate with results shown in
      the TP positive and 30% TS staining group. Prognosis was better in patients who
      had undergone postoperative adjuvant chemotherapy and had negative DPD, TP and TS
      staining. These findings suggest that TP and TS are prognostic factors of
      colorectal cancer and that staining results of DPD combined with either TS or TP
      indicate the efficacy of postoperative adjuvant chemotherapy.

PMID- 15446557
TI  - [Clinical study of irinotecan therapy in patients with fluoropyrimidine-resistant
      advanced colorectal cancer].
AB  - The clinical efficacy and safety of irinotecan (CPT-11) therapy were studied
      retrospectively in patients with fluoropyrimidine-resistant advanced colorectal
      cancer. The subjects were 44 patients who were treated with CPT-11 alone or with
      a combination of CPT-11 and mitomycin C (MMC) at our institute from April 1999 to
      March 2003. CPT-11 (120-150 mg/m2) alone or CPT-11 with MMC (5 mg/m2) was
      administered every 2 weeks. The objective overall response rate was 11% (95%
      confidence interval, 3.8-25%). In 38 patients who were treated until October
      2002, the median survival time was 12 months. Two-year survival rate was 13%.
      Grade 3 anorexia or diarrhea occurred in 6 patients (14%) and 5 patients (11%),
      respectively. There was no treatment-related death or early death within 30 days
      from the last administration of CPT-11 (+MMC). This retrospective study
      demonstrated the reproducible activity and safety of CPT-11 for the treatment of
      fluoropyrimidine-resistant advanced colorectal cancer in clinical practice.

PMID- 15446558
TI  - [Adjuvant chemotherapy for unresectable locally advanced pancreatic cancer in
      light of its characteristics].
AB  - The use of neoadjuvant chemotherapy for pancreatic cancer has been advocated for
      its potential ability to optimize patient selection for surgical resection and to
      downstage locally advanced tumors, especially for patients with Stage IV b (Japan
      criteria). We report our experience with a six-drug chemotherapeutic regimen that
      resulted in sufficient downstaging of the tumor in some patients to justify
      surgical resection. From Jan. 2001 through December 2003, 6 patients received 5
      FU as a continuous infusion (200 mg/m2/day), calcium leucovorin weekly by
      intravenous bolus injection (30 mg/m2), mitomycin-C every 6 weeks (10 mg/m2
      intravenously), and dipyridamole daily orally (75 mg), according to the UCLA
      regimen and gemcitabine weekly (600 mg/m2) and heparin as a continuous infusion
      (0-3,000 U/day) for locally advanced unresected pancreatic cancer. All of these
      patients were evaluable for response and survival. There were 5 partial responses
      (83% response rate) and 1 no response. Four of 5 responding patients had
      sufficient tumor regression to meet clinical criteria for resectability, three of
      whom underwent a curative resection. All patients who underwent downstage
      operation were still alive for the follow-up period (4-23 months).

PMID- 15446559
TI  - [Clinical study of gemcitabine therapy for recurrent or metastatic pancreatic
      cancer].
AB  - The clinical efficacy and safety of gemcitabine (GEM) monotherapy were studied
      retrospectively in the patients with recurrent or metastatic pancreatic cancer.
      The subjects were 30 patients who were treated with GEM at our center between May
      2001 and August 2003. The objective overall response rate was 11% (3/28; 95%
      confidence interval, 2.3-28%). The disease control rate (CR+PR+SD) was 54%. Grade
      3 or 4 neutropenia was most frequently seen in 46%. Non-hematological toxicities
      were mild. The median survival time was 4.8 months. One-year survival rate was
      15%. This study showed the reproducible activity and safety of GEM in practice.

PMID- 15446560
TI  - [A clinical study using octreotide in relieving gastrointestinal symptoms due to
      bowel obstruction in a terminally ill cancer patient].
AB  - Terminally ill cancer patients with complicated bowel obstructions often have
      poor quality of life (QOL) due to gastrointestinal symptoms such as nausea and
      vomiting. Many of these patients are inoperable because of poor general
      conditions, and half of these patients can't be managed by conventional
      antiemetics. There are many reports indicating octreotide is effective for these
      patients. In the present study, 13 patients (5 patients without a nasogastric
      tube and 8 patients with) were administered octreotide at 300 microg/day by 24
      hours continuous subcutaneous infusion. Among the effectively evaluable 10 cases,
      6 cases (60.0%) were assessed as effective according to the efficacy criteria
      based on the JCOG toxicity scale. In the 6 cases who had nasogastric tubes, the
      nasogastric aspirates decreased from 890 ml (550-1,950) to 480 ml (180-1,790).
      Vomiting was successfully controlled after the removals of nasogastric tubes in 4
      out of 6 cases (66.7%), regarding safety, 2 out of 13 cases (15.4%) showed an
      excess of liver enzymes but no clinically suspected adverse effect was observed.
      Octreotide is effective and well tolerated in terminally ill cancer patients with
      malignant bowel obstruction.

PMID- 15446561
TI  - [A case report--a patient with gingiva carcinoma showing complete remission after
      combination chemotherapy with nedaplatin and 5-fluorouracil].
AB  - We report a patient showing a complete remission after combination chemotherapy
      with nedaplatin and 5-fluorouracil (5-FU). A 63-year-old man was admitted to our
      hospital for advanced carcinoma of gingiva. 5-FU was administered at a dose of
      1,000 mg/body (700 mg/m2) by continuous infusion for 120 hours on days 1 to 5.
      Nedaplatin was administered at a dose of 140 mg/body (90 mg/m2) by drip infusion
      for 120 minutes on day 5. This combination chemotherapy resulted in a complete
      remission of the tumor after 2 weeks. There has been no sign of recurrence for 6
      months after the chemotherapy.

PMID- 15446562
TI  - [A long-surviving patient with Stage IV breast cancer with no recurrence after
      combined therapy of medroxy progesterone acetate (MPA) and intra-arterial
      infusion chemotherapy].
AB  - The patient is a 42-year-old woman who had advanced (Stage IV) right breast
      cancer with contralateral supraclavicular lymph node metastasis. She was treated
      with the combined use of MPA and the intra-arterial infusion chemotherapy. We
      administered EPI into the left subclavian artery and the right internal thoracic
      artery. Total dose of EPI was 210 mg. MPA was administered po at 1,200 mg/day
      daily. During the chemotherapy, she experienced only grade 2 alopecia. After the
      chemotherapy, the regressive change was noted in the primary lesion. The clinical
      response was evaluated CR. She underwent right modified mastectomy and the
      resection of contralateral supraclavicular lymph nodes. Although the clinical
      response was very good, the pathological effect was only Grade 1b. Eight years
      have passed since the operation, and the patient is still alive with no sign of
      recurrence. It is suggested that this combination therapy may be useful for
      advanced breast cancer and the like.

PMID- 15446563
TI  - [A case of liver metastases of breast cancer successfully treated by combination
      chemotherapy using hepatic arterial infusion of docetaxel and systemic
      administration of trastuzumab].
AB  - A 43-year-old woman underwent breast-conserving therapy for right breast cancer
      with multiple liver metastases (pT3N3aM1, stage IV, ER (-), PgR (-), HER2 (3+)),
      in November, 2002. Following surgery, she received combination chemotherapy using
      hepatic arterial infusion of docetaxel and systemic administration of trastuzumab
      weekly. During therapy, no serious side effects and only grade 1 nausea were
      observed; after 3 courses, therapy was safely continued on an outpatient basis.
      Metastatic liver tumors responded to the treatment, and they completely
      disappeared on an abdominal CT 5 months later. In addition, all elevated tumor
      markers in serum decreased to the normal range. No new metastatic or recurrent
      lesions were found 14 months after surgery. We conclude that this combination
      chemotherapy is safe and may be very useful for the treatment of breast cancer
      patients with liver metastasis.

PMID- 15446564
TI  - [Advanced non-small cell lung cancer responded to both vinorelbine and
      carboplatin over long-term outpatient treatment].
AB  - We treated a patient with lung adenocarcinoma who responded to chemotherapy with
      vinorelbine (VNR) plus carboplatin (CBDCA) on an outpatient basis. The patient
      was a 68-year-old man. He visited a local physician complaining of wet coughing,
      headache and general fatigne. The symptoms remained unchanged and the patient was
      admitted to our department for treatment in June 2000. A massive shadow in the
      right upper lobe and multiple cerebral metastases were found. Based on this, the
      diagnosis was lung adenocarcinoma (T3N2M1, clinical stage IV). Whole-brain
      irradiation and systemic chemotherapy were initiated from July 2000. The patient
      received 1 course of systemic chemotherapy with vindesine (VDS) plus cisplatin
      (CDDP) on an inpatient basis. This regimen was replaced with combination therapy
      of paclitaxel (TXL) plus CBDCA in the outpatient setting, along with VNR plus
      CBDCA due to side effects caused by TXL. The cerebral metastases almost
      disappeared due to whole-brain irradiation. Chest CT after 3 courses revealed a
      reduction in primary tumor size. The VNR plus CBDCA combination therapy was
      continued for a further 6 courses. As the result, neither the primary tumor nor
      the cerebral metastases enlarged. The combination therapy with VNR plus CBDCA
      seems to be a useful regimen that can maintain high QOL and be conducted for a
      long term on an outpatient basis.

PMID- 15446565
TI  - [A resected case of thoracic esophageal cancer in which pCR was obtained using
      low-dose of nedaplatin (CDGP)/5-FU and radiotherapy].
AB  - This is a report of a case with esophageal cancer in which pathological CR was
      obtained by neoadjvant chemoradiotherapy using a low-dose of nedaplatin (CDGP)/5
      FU. The patient was a male aged 76. A protuberant lesion diagnosed as esophageal
      cancer was found in the middle thoracic esophagus by esophagography. Since
      another lesion in the upper thoracic esophagus was revealed by endoscopy,
      metastasis to the cervical lymph nodes was diagnosed by ultrasonography, and
      preoperative chemoradiotherapy combining a low dose of CDGP/5-FU with
      radiotherapy was performed. As side effects of this treatment, grade 2 stomatitis
      and granulocytopenia were observed. The main lesion of the esophagus was found to
      have significantly diminished through endoscopy after completion of the
      treatment, and with no malignant cells obtained by biopsy. No cervical lymph
      nodes were found. It was diagnosed as partial response (PR) through imaging
      diagnosis. Radical resection of esophageal cancer under right thoracotomy and
      laparotomy was performed. Operative findings were Ch x R-T3N0M0 Stage II R0 D2
      Cur A. Pathological examination of resected specimens revealed no viable cancer
      cells in the esophagus or metastasis to the dissected lymph nodes. Neoadjuvant
      chemoradiotherapy using a low-dose of CDGP/5-FU is an effective treatment for
      esophageal cancer.

PMID- 15446566
TI  - [A case report of metastatic pancreatic cancer that responded remarkably to the
      combination of thalidomide, celecoxib and irinotecan].
AB  - The prognosis of pancreatic cancer with metastases or recurrence is quite poor.
      Chemotherapy has not resulted in a significant survival benefit; median survival
      is 3-6 months. Various chemotherapeutic agents have been evaluated and the
      standard chemotherapy of pancreatic cancer is gemcitabine. The response rate,
      however, is low at 13%. Thalidomide and celecoxib have different mechanisms of
      action and activity in various malignant tumors. Both have been evaluated and
      shown to demonstrate activity against solid tumors. Thalidomide decreased the
      stability of TNF-mRNA and COX-2 mRNA. COX-2 is a bifunctional enzyme possessing
      both cyclooxygenase and peroxidase activities. Although celecoxib inhibits PG
      biosynthesis, most do not affect the peroxidase activity of COX, which can
      generate proximate carcinogens. Because thalidomide does not completely inhibit
      COX-2 expression or PG biosynthesis, a therapeutic strategy combining celecoxib
      with thalidomide might be more effective than using either agent alone.
      Differences in the mechanism of action of gemcitabine and irinotecan suggest that
      a change of gemcitabine to irinotecan could provide clinically efficacious
      outcomes. In order to accomplish new treatment strategies, we have been using
      thalidomide, celecoxib and irinotecan in low-doses. We believe this combination
      represents a viable treatment for patients of pancreatic cancer with recurrence
      or metastases.

PMID- 15446567
TI  - [A case of giant hepatocellular carcinoma treatable with radio frequent ablation
      therapy after effective UFT administration].
AB  - A 71-year-old man was diagnosed with giant hepatocellular carcinoma (HCC) and
      hepatitis C cirrhosis at a nearby hospital. Image diagnosis showed no other
      metastasis, but the tumor was very huge with daughter nodules in the bilateral
      lobe of the liver. He was thus treated by oral administration of UFT (300
      mg/day). Two months later, the giant liver tumor had shrunk remarkably, and the
      daughter tumors had disappeared. Eight months later, the levels of serum AFP and
      PIVKA-II had also reduced remarkably. Twelve months following the first
      treatment, the levels of both serum AFP and PIVKA-II began increasing again, and
      he was referred to our hospital. CT showed 2 liver tumors, 1 of which showed
      viability with moderately differentiated hepatocellular carcinoma and the other
      evidencing necrosis histologically. Radio frequency ablation therapy was
      performed for 2 tumors by open laparotomy. It was considered that administration
      of UFT is a useful and safe therapy for far advanced HCC.

PMID- 15446568
TI  - [A case of metastatic liver tumor from colorectal carcinoma--continued arterial
      infusion chemotherapy through a microcatheter located in replaced right hepatic
      artery].
AB  - The patient was a 78-year-old male with a history of colon cancer. After surgical
      resection of colon cancer, he suffered a multiple liver metastasis. We treated
      him by arterial infusion chemotherapy with the catheter edge embedded at the
      common hepatic artery. For a long period, the lesions were defined as partial
      response on WHO-criteria, but a wide area of the common hepatic artery was
      shrunk. After changing the treatment to systemic intravenous chemotherapy, the
      metastatic lesions began to enlarge. Then, we somehow were able to put a
      microcatheter into the replaced right hepatic artery (rRHA), and could restart
      arterial infusion chemotherapy. We continued this procedure for over a year
      without any complication.

PMID- 15446569
TI  - [A case of recurrent stomach cancer treated with 5-fluorouracil responding to
      weekly paclitaxel therapy].
AB  - We report a patient with unresectable stage IV stomach cancer with metastasis to
      the paraaortic lymph nodes who achieved an effective response to neoajuvant
      chemotherapy, which allowed curability-B resection, and in whom weekly paclitaxel
      (TXL) therapy for postoperative recurrence was very effective in improving QOL.
      The patient was a 65-year-old man. After preoperative PMFE therapy, CEA decreased
      from 68.1 ng/ml to 0.8 ng/ml, and CA19-9 from 15,000 U/ml to 190 U/ml. The
      paraaortic lymph nodes disappeared, and stomach wall thickening decreased. The
      overall response to treatment was evaluated as a partial response (PR). After
      surgery, the patient was given TS-1, but became unable to take oral medication
      because of retroperitoneal and lymph node recurrence. Since the cancer appeared
      to be resistant to 5-fluorouracil (5-FU), the patient was treated by weekly TXL
      therapy. Increased appetite and weight gain were observed from the middle of the
      first course of therapy, and CEA decreased from 28.2 ng/ml to 4.9 ng/ml, and CA19
      9 from 15,000 U/ml to 2,000 U/ml. Abdominal CT scans demonstrated shrinkage of
      the tumor. Although the patient died 1 year and 8 months after the initial
      examination, he was able to take oral medication and maintain good QOL for 10
      months after the start of TXL therapy. Only grade 1 side effects (alopecia and
      leukopenia) were observed throughout the course. These results suggest that TXL
      therapy is effective also for 5-FU-resistant stomach cancer, and exhibits effects
      early even in patients in a poor general condition, causing only mild side
      effects, with early improvements in QOL.

PMID- 15446570
TI  - [A case of advanced gastric cancer with peritonitis carcinomatosa resected with
      intraperitoneal chemotherapy based on chemosensitivity test with ascites].
AB  - The patient was a 57-year-old man who developed obstructive jaundice and
      pancreatitis. He was diagnosed with peritonitis carcinomatosa from gastric
      cancer, and the cancers were unresectable at first laparotomy. We gathered the
      accumulated ascites and examined the fluid by chemosensitivity test. Some anti
      cancer drugs were selected based on the test results of test, and four cycles of
      modified PMUE therapy (CDDP ip, MMC iv, ETP po, UFT-E po) were performed. This
      chemotherapy proved very effective, and the cytodiagnostic malignancy with
      ascites changed from class V to II before and after chemotherapy. Following
      chemotherapy, a re-laparotomy was performed and a curability B operation could be
      undertaken. He survived for 17 months after the first laparotomy, but died of
      extra-peritoneal recurrence in the pelvic cavity. Treatment of advanced gastric
      cancers with peritonitis carcinomatosa is very difficult, because none of the
      various therapies (operation, chemotherapy, hyperthermia etc.) can completely
      control dissemination. It is very effective when the chemosensitivity of
      individual cancers is clear before chemotherapy. The current chemosensitivity
      test with ascites is still technically incomplete, but it may contribute to
      improved treatment of cancers with peritonitis carcinomatosa in the future.

PMID- 15446571
TI  - [A case of 5-FU-resistant recurrent colon cancer treated with low-dose CPT
      11/CDDP on an outpatient basis].
AB  - We report a case of recurrent colon cancer resistant to 5-FU, whose QOL and PS
      has been well maintained with low-dose CPT-11/CDDP administered on an outpatient
      basis for more than 28 months. A 42-year-old male had lymph node recurrence 27
      months after curative resection of colon cancer. He had been administered
      pharmacokinetic modulating chemotherapy (PMC, oral tegafur/uracil plus
      fluorouracil infusion) after surgery. Combined treatment with CPT-11 (50
      mg/m2)/CDDP (6 mg/m2) was performed on an outpatient basis. Nine months of NC was
      obtained without any severe side effect. Modified administration of this
      treatment with 5'-DFUR and TS-1 lead to further maintenance of quality of life
      and performance status. This case suggests the efficacy of low-dose CPT-11/CDDP
      for cases of 5-FU-resistant colon cancer in terms of QOL and PS.

PMID- 15446572
TI  - [Orotate phosphoribosyl transferase in bladder cancer].
AB  - 5-fluorouracil (5-FU) is an anticancer agent widely used against various tumors
      including bladder cancer. Orotate phosphoribosyl transferase (OPRT) is one of the
      key enzymes in metabolic pathways of 5-FU. We examined the possible relationship
      between OPRT activities of bladder cancer specimens and clinicopathological
      features. In addition, chemosensitivity to 5-FU was also examined. Bladder cancer
      specimens were obtained from 36 patients between November 1997 and January 2004.
      OPRT activity was measured by radioassay. In vitro chemosensitivity to 5-FU was
      assessed using histoculture drug response assay (HDRA). The mean OPRT activity in
      bladder cancer specimens was significantly higher than that in normal bladder
      specimens. In high-grade (G3) and invasive cancer specimens, mean OPRT activities
      were significantly higher than those in low grade (G1 and G2) and superficial
      cancer specimens, respectively. There was a significant correlation between OPRT
      activity and 5-FU sensitivity (r=0.571, p<0.01) in 19 cases whose OPRT activities
      and 5-FU sensitivities were assessed simultaneously. These results suggest that
      OPRT activity may be a good indicator of the malignant potential and sensitivity
      to 5-FU in bladder cancer.

PMID- 15446573
TI  - [A review and development of sentinel node navigation surgery for lung cancer].
AB  - Sentinel node navigation surgery (SNNS) for lung caner has not yet been
      established. Sentinel node (SN) identification using dye or radioisotope has been
      developed; however, the SN identification rate was less than 50% in the dye
      method and use of radioisotopes is strongly restricted in Japan. The novel method
      using a CT or MRI contrast medium are expected. A study of local immune reaction
      for lung cancer in SN is also a very interesting issue.

PMID- 15446574
TI  - [Tumor markers for pancreatic and biliary tract cancer].
AB  - There are a variety of tumor markers used for diagnosis of pancreatic and biliary
      tract cancer including carbohydrate antigens such as CA19-9, DUPAN-2, CA50 and
      Span-1, the carcinoembryonic antigen and pancreatic enzymes such as elastase 1.
      The tumor marker kinetics in serum help to predict survival in patients receiving
      surgical and/or non-surgical treatment. Since each of those tumor markers remains
      at a low sensitivity and specificity in the early stage, none are useful for
      detecting early cancer. In spite of the development of various diagnostic
      techniques, pancreas and biliary tract cancer is usually diagnosed at an
      incurable stage, and the 5-year survival rate is extremely low. Therefore,
      improvements in survival may well result from screening for early-stage
      pancreatic and biliary cancer. The development of tumor markers with higher
      sensitivity and specificity should have the highest priority.

PMID- 15446575
TI  - The Joint Commission announces the 2005 National Patient Safety Goals and
      requirements.

PMID- 15446576
TI  - Expanded Joint Commission Corporate Scorecard addresses new accreditation
      process.

PMID- 15446577
TI  - Joint Commission revises scoring category, measure of success designations,
      scoring category definitions, and sample size descriptions.

PMID- 15446578
TI  - Direct stimulation of adult neural stem cells in vitro and neurogenesis in vivo
      by vascular endothelial growth factor.
AB  - Hypoxia as well as global and focal ischemia are strong activators of
      neurogenesis in the adult mammalian central nervous system. Here we show that the
      hypoxia-inducible vascular endothelial growth factor (VEGF) and its receptor
      VEGFR-2/Flk-1 are expressed in clonally-derived adult rat neural stem cells in
      vitro. VEGF stimulated the expansion of neural stem cells whereas blockade of
      VEGFR-2/Flk-1-kinase activity reduced neural stem cell expansion. VEGF was also
      infused into the lateral ventricle to study changes in neurogenesis in the
      ventricle wall, olfactory bulb and hippocampus. Using a low dose (2.4 ng/d) to
      avoid endothelial proliferation and changes in vascular permeability, VEGF
      stimulated adult neurogenesis in vivo. After VEGF infusion, we observed reduced
      apoptosis but unaltered proliferation suggesting a survival promoting effect of
      VEGF in neural progenitor cells. Strong expression of VEGFR-2/Flk-1 was detected
      in the ventricle wall adjacent to the choroid plexus, a site of significant VEGF
      production, which suggests a paracrine function of endogenous VEGF on neural stem
      cells in vivo. We propose that VEGF acts as a trophic factor for neural stem
      cells in vitro and for sustained neurogenesis in the adult nervous system. These
      findings may have implications for the pathogenesis and therapy of
      neurodegenerative diseases.

PMID- 15446579
TI  - Entorhinal cortex lesion in the mouse induces transsynaptic death of perforant
      path target neurons.
AB  - Entorhinal cortex lesion (ECL) is a well described model of anterograde axonal
      degeneration, subsequent sprouting and reactive synaptogenesis in the
      hippocampus. Here, we show that such lesions induce transsynaptic degeneration of
      the target cells of the lesions pathway in the dentate gyrus. Peaking between 24
      and 36 hours post-lesion, dying neurons were labeled with DeOlmos silver-staining
      and antisera against activated caspase 3 (CCP32), a downstream inductor of
      programmed cell death. Within caspase 3-positive neurons, fragmented nuclei were
      co-localized using Hoechst 33342 staining. Chromatin condensation and nuclear
      fragmentation were also evident in semithin sections and at the ultrastructural
      level, where virtually all caspase 3-positive neurons showed these hallmarks of
      apoptosis. There is a well-described upregulation of the apoptosis-inducing
      CD95/L system within the CNS after trauma, yet a comparison of caspase 3-staining
      patterns between CD95 (Ipr)- and CD95L (gld)-deficient with non-deficient mice
      (C57/bl6) provided no evidence for CD95L-mediated neuronal cell death in this
      setting. However, inhibition of NMDA receptors with MK-801 completely suppressed
      caspase 3 activation, pointing to glutamate neurotoxicity as the upstream inducer
      of the observed cell death. Thus, these data show that axonal injury in the CNS
      does not only damage the axotomized neurons themselves, but can also lethally
      affect their target cells, apparently by activating glutamate-mediated
      intracellular pathways of programmed cell death.

PMID- 15446580
TI  - Subclassification of nerve sheath tumors by gene expression profiling.
AB  - Nerve sheath tumors are the most common tumors of Neurofibromatosis type 1 (NF1)
      patients. Dermal neurofibromas develop in nearly all NF1-patients, whereas
      plexiform neurofibromas are only observed in one-third of the patients. NF1
      patients have about a 10% lifetime risk for developing malignant pheripheral
      nerve sheath tumors (MPNST). The origin of these tumors is thought to be the
      Schwann cell lacking functional neurofibromin. However, additional genetic
      alterations are likely to modulate tumor biology and to contribute to individual
      nerve sheath tumor entities. To gain insight into the molecular events and to
      determine whether these tumors can be classified according to gene expression
      profiles, we performed expression analysis applying cDNA array technology. Nine
      dermal neurofibromas, 7 plexiform neurofibromas, ten MPNST and two MPNST cell
      cultures were examined. All tumors but 6 sporadic MPNST were obtained from NF1
      patients. We detected significant differences in gene expression patterns between
      neurofibromas and MPNST and between dermal neurofibromas and plexiform
      neurofibromas. Tumor class prediction agreed in all but one case with
      histological and clinical classification. NF1-associated and sporadic MPNST could
      not be distinguished by their gene expression patterns. We present a panel of
      discriminating genes that may assist subclassification of nerve sheath tumors.

PMID- 15446581
TI  - Interferon-gamma expression in periventricular leukomalacia in the human brain.
AB  - Periventricular leukomalacia (PVL), the major lesion underlying cerebral palsy in
      survivors of prematurity, is characterized by focal periventricular necrosis and
      diffuse gliosis of immature cerebral white matter. Causal roles have been
      ascribed to hypoxiaischemia and maternal-fetal infection, leading to cytokine
      responses, inflammation, and oligodendrocyte cell death. Because interferon-gamma
      (IFN-gamma) is directly toxic to immature oligodendrocytes, we tested the
      hypothesis that it is expressed in PVL (N = 13) compared to age-adjusted controls
      (N = 31) using immunocytochemistry. In PVL, IFN-gamma immunopositive macrophages
      were clustered in necrotic foci, and IFN-gamma immunopositive reactive astrocytes
      were present throughout the surrounding white matter (WM). The difference in the
      number of IFN-gamma immunopositive glial cells/high power field (IFN-gamma score,
      Grades 0-3) between PVL cases (age-adjusted mean 2.59+/-0.25) and controls (age
      adjusted mean 1.39+/-0.16) was significant (p<0.001). In the gliotic WM, the IFN
      gamma score correlated with markers for lipid peroxidation, but not nitrative
      stress. A subset of premyelinating (04+) oligodendrocytes expressed IFN-gamma
      receptors in PVL and control cases, indicating that these cells are vulnerable to
      IFN-gamma toxicity via receptor-mediated interactions. In PVL, IFN-gamma produced
      by macrophages and reactive astrocytes may play a role in cytokine-induced
      toxicity to premyelinating oligodendrocytes as part of a cytokine response
      stimulated by ischemia and/or infection.

PMID- 15446582
TI  - Gene expression profiles of reactive astrocytes in dopamine-depleted striatum.
AB  - We have used cDNA array analysis to examine the expression of genes in reactive
      astrocytes of dopamine-depleted striatum of rats in vivo, an animal model for
      Parkinson disease, compared to those from control striatum. The striatum of both
      normal adult rats and rats whose substantia nigra had been lesioned with 6
      hydroxydopamine was removed one week following lesion. After fixing the tissue in
      RNAlater, individual astrocytes, isolated directly from dissociated striatum and
      confirmed to be astocytes by expression of glial fibrillary acidic protein (GFAP)
      mRNA using single cell RT-PCR, were used as the source of mRNA. Co-localization
      of GFAP with either of 2 antibodies known to label only reactive astrocytes in
      vivo confirmed that virtually all astrocytes in the lesioned striatum were
      reactive. The analysis has identified 29 genes whose expression is turned on or
      enhanced in dopamine-depleted striatal astrocytes and 2 whose expression is
      decreased. In situ hybridization was used to confirm the localization of 8 of
      these genes to astrocytes: these included GDNF, NGF, bFGF, TNF-alpha, MIP-1alpha,
      c-jun, Fra-1 and Fra-2. Understanding these gene differences that occur in
      astrocytes in response to dopamine depletion should enhance our ability to
      promote recovery from the injury.

PMID- 15446583
TI  - Genetic and expression profiles of cerebellar liponeurocytomas.
AB  - Cerebellar liponeurocytoma, a rare, newly identified CNS neoplasm of adults, is
      characterized by advanced neuronal/neurocytic and focal lipomatous
      differentiation, low proliferative potential and a favorable clinical prognosis.
      Despite the different age distribution and benign biological behavior, the
      cerebellar liponeurocytoma shares several features with the cerebellar
      medulloblastoma, which may include an origin from the periventricular matrix of
      the fourth ventricle or the external granular layer of the cerebellum. To
      establish the genetic profile of cerebellar liponeurocytomas, we have formed an
      international consortium and collected tumor samples from 20 patients. DNA
      sequencing revealed TP53 missense mutations in 4 (20%) of 20 cerebellar
      liponeurocytomas, a frequency higher than in medulloblastomas. There was no case
      with PTCH, APC, or beta-catenin mutations, each of which may be present in
      subsets of medulloblastomas. Isochromosome 17q, a genetic hallmark of classic
      medulloblastomas, was not observed in any of the cases investigated by FISH
      analysis. cDNA array analyses were carried out on 4 cerebellar liponeurocytomas,
      4 central neurocytomas, and 4 classic medulloblastomas. Cluster analysis of the
      cDNA expression data of 1176 genes grouped cerebellar liponeurocytomas close to
      central neurocytomas, but distinct from medulloblastomas. These results suggest
      cerebellar liponeurocytoma as a distinct tumor entity that is genetically
      different from medulloblastoma. Furthermore, the cDNA expression array data
      suggest a relationship to central neurocytomas, but the presence of TP53
      mutations, which are absent in central neurocytomas, suggests that their genetic
      pathways are different.

PMID- 15446584
TI  - A pathogenic peripherin gene mutation in a patient with amyotrophic lateral
      sclerosis.
AB  - Peripherin is a neuronal intermediate filament protein that is expressed chiefly
      in motor neurons and other nerve cells that project into the peripheral nervous
      system. Transgenic mice that over-express peripherin develop motor neuron
      degeneration, suggesting that mutations in peripherin could contribute to the
      development of motor neuron disease. In this paper, we report the identification
      of a homozygous mutation in the peripherin gene (PRPH) in a patient with
      amyotrophic lateral sclerosis (ALS). The mutation resulted in a substitution of
      aspartate with tyrosine at amino acid position 141, which is located within the
      first linker region of the rod domain. Immunocytochemical analysis of the spinal
      cord of the patient upon autopsy revealed distinctive large aggregates within the
      cell bodies of residual spinal motor neurons that contained peripherin and was
      also immunoreactive with antibodies to the neurofilament proteins. In order to
      study the effect of the mutation on peripherin assembly, we performed transient
      transfections. Unlike wild-type peripherin, which self-assembles to form a
      filamentous network, the mutant peripherin was prone to form aggregates in
      transfected cells, indicating that the mutation adversely affects peripherin
      assembly. Moreover, the neurofilament light (NF-L) protein was not able to rescue
      the mutant protein from forming aggregates. These data imply that mutation of
      PRPH is a contributing factor for ALS.

PMID- 15446585
TI  - Gene expression profiling reveals unique molecular subtypes of Neurofibromatosis
      Type I-associated and sporadic malignant peripheral nerve sheath tumors.
AB  - Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive Schwann
      cell neoplasms that are frequently associated with Type I Neurofibromatosis (NF1)
      and respond poorly to current therapeutic regimens. To better understand the
      molecular heterogeneity of these tumors, we performed gene expression profiling
      on 25 NF1-associated and 17 sporadic MPNSTs using oligonucleotide microarrays
      representing approximately 8100 unique human gene transcripts. Using several
      previously reported statistical approaches, we were unable to identify a
      molecular signature that could reliably distinguish between NF1-associated and
      sporadic MPNSTs in independent training and test sample sets. However, using an
      unsupervised clustering approach, we identified an extensive gene expression
      signature that distinguished 9 of the 42 tumors analyzed. This signature
      corresponded to relative overexpression of transcripts associated with neuroglial
      differentiation (NCAM, MBP, L1CAM, P1P) and relative down-regulation of
      proliferation and growth factor associated transcripts (IGF2, FGFR1, MDK, Ki67).
      All tumors with this gene expression signature lacked expression of EGFR and all
      but one tumor were derived from patients with NF1. However, there were no other
      obvious associations with histological grade, tumor site, metastasis, recurrence,
      age, or patient survival. We conclude that distinct molecular classes of MPNST
      exist and that the ability to stratify these tumors based on unique and
      biologically relevant gene expression profiles may be important for future
      targeted therapeutics.

PMID- 15446586
TI  - The pathogenesis of neonatal post-hemorrhagic hydrocephalus.
AB  - Hydrocephalus after intraventricular hemorrhage (IVH) has emerged as a major
      complication of preterm birth and is especially problematic to treat. The
      hydrocephalus is usually ascribed to fibrosing arachnoiditis, meningeal fibrosis
      and subependymal gliosis, which impair flow and resorption of cerebrospinal fluid
      (CSF). Recent experimental studies have suggested that acute parenchymal
      compression and ischemic damage, and increased parenchymal and perivascular
      deposition of extracellular matrix proteins--probably due at least partly to
      upregulation of transforming growth factor-beta (TGF-beta)--are further important
      contributors to the development of the hydrocephalus. IVH is associated with
      damage to periventricular white matter and the damage is exacerbated by the
      development of hydrocephalus; combinations of pressure, distortion, ischaemia,
      inflammation, and free radical-mediated injury are probably responsible. The
      damage to white matter accounts for the high frequency of cerebral palsy in this
      group of infants. The identification of mechanisms and mediators of hydrocephalus
      and white matter damage is leading to the development of new treatments to
      prevent permanent hydrocephalus and its neurological complications, and to avoid
      shunt dependence.

PMID- 15446587
TI  - Insights into the pathogenesis of hydrocephalus from transgenic and experimental
      animal models.
AB  - Hydrocephalus is a progressive brain disorder characterized by abnormalities in
      the flow of cerebrospinal fluid (CSF) and ventricular dilatation that leads to
      cerebral atrophy, and if left untreated, can be fatal. Genetic mutations,
      congenital malformations, infectious diseases, intracerebral hemorrhages and
      tumors are common conditions resulting in hydrocephalus. Although the causes of
      obstructive hydrocephalus are better understood, the mechanisms resulting in
      chronic, progressive communicating congenital and acquired hydrocephalus are less
      well understood. In this regard, recent studies in transgenic (tg) mice suggest
      that increased expression of cytokines such as TGF-beta1 might play an important
      role by disrupting the vascular extracellular matrix (ECM) remodeling, promoting
      hemorrhages, and altering the reabsorption of CSF. In this context, the main
      objective of this manuscript is to provide an overview on the cellular and
      molecular mechanisms of hydrocephalus based on studies derived from tg and
      experimental animal models.

PMID- 15446588
TI  - Cellular damage and prevention in childhood hydrocephalus.
AB  - The literature concerning brain damage due to hydrocephalus, especially in
      children and animal models, is reviewed. The following conclusions are reached:
      1. Hydrocephalus has a deleterious effect on brain that is dependent on magnitude
      and duration of ventriculomegaly and modified by the age of onset. 2. Animal
      models have many histopathological similarities to humans and can be used to
      understand the pathogenesis of brain damage. 3. Periventricular axons and myelin
      are the primary targets of injury. The pathogenesis has similarities to traumatic
      and ischemic white matter injury. Secondary changes in neurons reflect
      compensation to the stress or ultimately the disconnection. 4. Altered efflux of
      extracellular fluid could result in accumulation of waste products that might
      interfere with neuron function. Further research is needed in this as well as the
      blood-brain barrier in hydrocephalus. 5. Some, but not all, of the changes are
      preventable by shunting CSF. However, axon loss cannot be reversed, therefore
      shunting in a given case must be considered carefully. 6. Experimental work has
      so far failed to show any benefit in reducing CSF production. Pharmacologic
      protection of the brain, at least as a temporary measure, holds some promise but
      more pre-clinical research is required.

PMID- 15446589
TI  - Chronic hydrocephalus in adults.
AB  - Chronic hydrocephalus is a complex condition, the incidence of which increases
      with increasing age. It is characterised by the presence of ventricular
      enlargement in the absence of significant elevations of intracranial pressure.
      The clinical syndrome may develop either as a result of decompensation of a
      "compensated" congenital hydrocephalus, or it may arise de novo in adult life
      secondary to a known acquired disturbance of normal CSF dynamics. The latter may
      be due to late onset acqueductal stenosis or disruption of normal CSF absorptive
      pathways following subarachnoid hemorrhage or meningitis ("secondary" normal
      pressure hydrocephalus (NPH)). In some cases the cause of the hydrocephalus
      remains obscure ("idiopathic" NPH). In all forms of chronic hydrocephalus the
      clinical course of the disease is heavily influenced by changes in the brain
      associated with aging, in particular cerebrovascular disease. Recent research has
      challenged previously held tenets regarding the CSF circulatory system and this
      in turn has led to a radical rethinking of the pathophysiological basis of
      chronic hydrocephalus.

PMID- 15446590
TI  - January 2004: elderly Filipino man with frontal lobe tumor.
AB  - A 74-year-old Filipino man presented with new-onset partial-complex seizures.
      Eight months earlier he had a subtotal gastrectomy for adenocarcinoma classified
      as T1 N0M0 stage IA. He was irradiated. Two months later, he became confused and
      developed rhythmic, seizure-like movements of the extremities. A head CT revealed
      a 2 cm. right frontal lobe mass. On MRI, the mass exhibited ring enhancement and
      was surrounded by edematous white matter. The patient denied headache, weakness
      or constitutional symptoms. CT of the chest and abdomen revealed no evidence of
      metastatic spread or other abnormalities. His seizures were controlled with
      fosphenytoin and dexamethasone. Preoperatively the frontal lobe lesion was
      considered most likely to be either a metastatic or primary tumor. Resection of
      the frontal lobe lesion revealed a firm gliotic cystic mass. Crush preparations
      and frozen sections showed acute and chronic inflammation, gliosis, fibrosis, and
      many foreign body giant cells reacting to parasitic larval tissue. Intact and
      necrotic larval parts were surrounded by gliotic brain tissue containing foreign
      body giant cells, macrophages, and lymphocytes. However, eosinophils were not
      seen. Finally a refractive fragment resembling a hooklet and a fragmented scolex
      were identified that made a diagnosis of cysticercosis certain.

PMID- 15446591
TI  - February 2004: a 44-year-old man with a 2-year history of epistaxis.
AB  - A 44-year old man presented with a 2-year history of epistaxis and a nodular
      lesion in the nasopharyngeal mucosa. Neuroimaging revealed a midline
      nasopharyngeal tumor extending through the skull base to the clivus. Following
      surgical resection, histological studies showed a paraganglioma, a tumor with a
      typical nesting pattern, abundant capillary network, and strong immunoreactivity
      for neuroendocrine markers. Paragangliomas of the head and neck are rare tumors,
      which may come to the neuropathologist's attention because of their propensity
      for intracranial spread. In particular, paragangliomas located in the nasopharynx
      may generate diagnostic difficulties, as they appear to have no connection with
      major paraganglia in the region. Morphologic criteria do not allow distinguishing
      between benign and malignant forms.

PMID- 15446592
TI  - March 2004: a 24-year-old woman with bifrontal headaches.
AB  - A 24-year-old woman with bifrontal headaches was found to have a well
      circumscribed lesion in the frontal lobe subcortical white matter. Microscopic
      examination showed clusters of small round cells separated by hypocellular
      neuropil-like areas, and a distinct border between tumor and surrounding white
      matter. Synaptophysin was diffusely positive in neuropil-like areas, and many
      tumor cells expressed NeuN. Based on these findings, a diagnosis of
      "extraventricular neurocytoma" was made. A double-label immunofluorescence stain
      was performed with NeuN and Ki-67 antibodies to determine if NeuN+ cells remained
      in the mitotic cycle. No colocalization of these markers was found, thus
      supporting the hypothesis that neuronal differentiation (as marked by NeuN
      expression) is incompatible with continued proliferation of tumor cells, as well
      as normal neurons.

PMID- 15446593
TI  - [Classification of lupus glomerulonephritis by ISN/RPS 2003: points of
      classification and the diagnostic manual].

PMID- 15446594
TI  - [My life work with colleagues on the kidney].

PMID- 15446595
TI  - [Laparoscopic live donor nephrectomy].

PMID- 15446596
TI  - [ABO-incompatible renal transplantation].

PMID- 15446597
TI  - [Clinical significance of the terminal complement complex in children with type I
      membranoproliferative glomerulonephritis].
AB  - We measured the concentrations of terminal complement complex (TCC) in plasma (n
      =25) and urine (n=13) using an enzyme-linked immunosorbent assay in pediatric
      patients with type I membranoproliferative glomerulonephritis(MPGN). Frozen
      tissue from 18 renal biopsies was evaluated for the presence of TCC by direct
      immunoperoxidase staining. In the acute phase of the disease, TCC concentrations
      in plasma were elevated above 0.5 AU/ml in 14 of 25 patients (High TCC group),
      while the remaining 11 patients showed less than 0.5 AU/ml (Low TCC group). In
      the High TCC group, TCC was deposited more diffusely and intensely in the
      glomerulus, compared to that in the Low TCC group (p= 0.034). Furthermore,
      urinary TCC concentrations in the High TCC group were higher than those in the
      Low TCC group (p=0.0001). The High TCC group showed not only a poorer response to
      steroid treatment, but also a poorer prognosis than the Low TCC group. These
      results suggest that, in pediatric patients with type I MPGN, TCC in circulation
      may play a certain role in TCC formation in the glomerulus and in urine. The TCC
      concentration in plasma could be used as a marker of responsiveness to steroid
      treatment and long-term prognosis.

PMID- 15446598
TI  - [Levels of serum ascorbate and its metabolites in hemodialysis patients].
AB  - The status of ascorbic acid (AA) in dialysis patients is the subject of debate.
      Some reports have found AA to be deficient in dialysis patients, while others
      have found that AA is not deficient. In an attempt to confirm AA serum
      concentrations in dialysis patients, we analyzed the concentrations of AA as well
      as its metabolites using the specific determination of AA with chemical
      derivatization and the HPLC method. We studied 131 patients under maintenance
      hemodialysis therapy (HD), 23 patients with chronic renal failure (CRF) and 48
      healthy controls (C). Serum concentrations of AA and the AA metabolites
      dehydroascorbic acid (DHA) and 2, 3-diketogulonate (DKG) were measured by HPLC.
      Nine HD patients were taking AA supplements. Seventy-six (62.3%) of the 122 HD
      patients not taking AA supplements exhibited deficient levels of AA (< 20
      microM), while 13 (56.5%) of the 23 CRF patients and 9 (18.8%) of the 48 C showed
      deficient levels of AA. Analysis of AA metabolites in the normal-range AA (20-80
      microM) group revealed that the DHA/AA ratio in HD patients was significantly
      higher than in C (3.3 +/- 2.6% and 1.2 +/- 2.2%, respectively). The DKG/AA ratio
      in HD patients was higher than in CRF patients (3.6 +/- 5.2% vs. 0.9 +/- 1.9%),
      whereas DKG was not detected in C. When compared to serum levels before the start
      of dialysis, serum AA, DHA and DKG concentrations at the end of the dialysis
      session decreased by an average of 74.2, 84.0 and 78.8% respectively. In HD
      patients, serum levels of thiobarbituric reactive substances (TBARS) were
      significantly lower in the higher AA (> 80 microM) group than in the deficient
      and normal-range AA groups. In 12 AA-deficient patients, after 1 month of taking
      AA supplements (200 mg/day), serum AA levels rose to 79.9 microM, while serum
      TBARS level declined when compared with levels before supplementation. In
      conclusion, the frequency of AA deficiency in dialysis patients is extremely
      high. AA deficiency in HD patients may result in high TBARS levels, which reflect
      increased oxidative stress. Adequate AA supplementation should therefore be
      considered in such patients.

PMID- 15446599
TI  - [Effects of nitrendipine on circadian variation of blood pressure in inpatients
      with renal parenchymal hypertension: assessment by ambulatory blood pressure
      monitoring].
AB  - OBJECTIVE: To study the effect of once-daily administration of a nitrendipine
      tablet 10 mg on 24-hour ambulatory blood pressure in inpatients with renal
      parenchymal hypertension. METHODS: Sixteen patients participated in the present
      study, and one patient was withdrawn because the baseline office blood pressure
      was less than 140/90 mmHg. In the baseline period, ambulatory blood pressure was
      monitored every 30 minutes for 30 hours. After the baseline measurement,
      nitrendipine 10 mg was orally administered once daily every morning for 7 days.
      The 30-hour ambulatory blood pressure monitoring was repeated after Day 6.
      RESULTS: Fifteen patients (aged 64.9 +/- 15.0 years) completed the study
      protocol. Baseline office blood pressure was 157.9 +/- 17.5/84.7 +/- 12.5 mmHg
      (mean +/- SD). Nitrendipine 10 mg tablets significantly reduced both systolic
      blood pressure (SBP) and diastolic blood pressure (DBP) at least for 11 hours
      after administration compared with those at baseline. The rate of "Decrease"
      (reduction in blood pressure > or = 20/10 mmHg and/or achieved blood pressure <
      140/90 mmHg at trough point) was 60.0% (9/15). Eleven patients were considered as
      effective cases at peak point (maximal reduction in blood pressure > or = 20/10
      mmHg). The rate of "Decrease" in effective cases at peak point was 72.7% (8/11).
      CONCLUSION: These results suggest that a once-daily administration of
      nitrendipine 10 mg tablets is effective for the 24-hour control of blood pressure
      in patients with renal parenchymal hypertension.

PMID- 15446600
TI  - [Angiotensin type 1 receptor blocker reduced proteinuria in patients of focal
      glomerular sclerosis].
AB  - We report three cases of focal glomerular sclerosis (FGS) with proteinuria that
      improved with the administration of angiotensin type 1 receptor blocker (ARB,
      losartan or valsartan). These three patients were a 41-year-old male (case 1), a
      22-year-old male (case 2) and a 47-year-old male (case 3), who showed
      proteinuria, renal dysfunction, and hyperlipidemia. In case 1, proteinuria and
      renal dysfunction were improved by losartan administration and low protein diet
      therapy. In case 2, losartan with steroid and immunosuppressant led to the
      complete remission of proteinuria, improvement of renal dysfunction and reduction
      of the glomerular injury score from repeat biopsy specimen by approximately 20%.
      In case 3, proteinuria was reduced by valsartan administration with steroid and
      immunosuppressant therapy. ARB treatment with steroid and immunosuppressant might
      be more effective on the reduction of proteinuria in FGS patients.

PMID- 15446601
TI  - Cultural diversity in leadership.

PMID- 15446602
TI  - Cultural diversity in leadership.

PMID- 15446603
TI  - Mentoring the minority nurse leader of tomorrow.
AB  - Diversity is crucial to the future of nursing. And fortunately, a shift in the
      composition of the nursing workforce so that it more accurately mirrors the
      composition of America's patient population is already taking place. However,
      this emerging multiculturalism brings an important issue to the forefront-the
      leadership tier in healthcare organizations must also reflect the ethnic and
      cultural changes taking place. Movement in this direction makes prominent the
      importance of the mentor role in the life of the minority nurse seeking a
      leadership career path. Acknowledging the present demographics of the profession,
      it is most unlikely that the mentor and mentee will be a cultural or ethnic
      match. The good news is that this should not be viewed as an automatic barrier.
      This article describes the 5 Cs of mentoring a minority nurse professional, that
      is, candor, compromise, confidence, complexity, and champion-the specific
      competencies that promote a mentor-mentee relationship focused on career success.

PMID- 15446604
TI  - African American nurse leadership: pathways and opportunities.
AB  - Leadership is required to ameliorate the gaps in health disparities that exist in
      the United States. Many experiential pathways exist for acquiring the leadership
      knowledge and skills required to lead change that results in healthcare
      improvement. Nurses who lead professional nursing associations and work with
      community organizations are capable of leading such community change efforts.
      Community leadership is a viable pathway for developing nurse leaders.

PMID- 15446605
TI  - Leadership development of Hispanic nurses.
AB  - The underrepresentation of racial and ethnic minority nurses and other health
      professions has been linked to the continued disparities in health outcomes for
      these populations (Institute of Medicine. Unequal Treatment. Confronting Racial
      and Ethnic Disparities in Health Care. Washington, DC: The National Academies
      Press; 2002). Strategies to reduce health disparities, such as increasing the
      cultural competence of majority nurses, often depend on leaders of the same
      racial and ethnic groups to provide leadership in research, education, practice,
      and communities. However, little is known about the leadership pathways of racial
      and ethnic minority nurses. In this descriptive study, 22 Hispanic nurse leaders
      completed an open-ended survey related to their definitions of leadership, and
      challenges and opportunities in their leadership development. Although there are
      similarities in many aspects of leadership development, the lack of Hispanics in
      the workplace, the ability and responsibilities related to being bilingual and
      bicultural, and perceived discrimination in the work setting are additional
      challenges identified by Hispanic nurses. The importance of role models and
      mentors in facilitating leadership development is a dominant theme. Results of
      this study provide direction not only for the development of leadership for
      Hispanic nurses but also for other racial and ethnic minority nurses.

PMID- 15446606
TI  - Leadership to reduce health disparities: a model for nursing leadership in
      American Indian communities.
AB  - Health disparities can be especially dramatic for American Indians because of a
      variety of powerful forces that include poverty, isolation, low educational
      achievement, and a unique political relationship that dictates the design of
      special healthcare delivery mechanisms. The challenge facing nursing leaders in
      these setting is addressed with consideration to culture, an examination of why
      leadership is needed to change the forces that lead to health disparities, the
      role of leadership in reducing ethnic disparities in health outcomes, as well as
      an examination of the most productive ways to mobilize nurses and nursing
      leadership to address the problems. A model for nursing leadership in Native
      American communities is proposed and a case study that illustrates how culturally
      diverse leadership in a public health setting can maximize results is presented.

PMID- 15446607
TI  - Leadership from an international perspective.
AB  - Leadership development can be considered from its science, which addresses
      business skills, and it can be considered from the art of leadership, which
      addresses the management of relationships. There is also the third frame of the
      "leader within." In this frame, art and science are blended, melded, and matured
      into the unique shape of each individual's expression of leadership behavior.
      This third perspective also addresses the cultural diversity of leadership. It
      permits a comparison of the American leadership experience with the evolving
      leadership development in Central and Eastern Europe (CEE). The framework used to
      discuss cultural diversity of leadership development is the Center for Nursing
      Leadership's Dimensions of Leadership. These dimensions are a set of values,
      beliefs, and behaviors that look at leadership beyond the traditional skill sets.
      The dimensions include (1) holding the truth; (2) quest for adventure toward
      knowing; (3) appreciation of ambiguity; (4) holding multiple perspectives without
      judgment; (5) discovery of potential; (6) nurturing the emotional and
      intellectual self; (7) keeping commitments to oneself; and (9) diversity as a
      vehicle to wholeness. These dimensions explore emerging leadership shifts
      occuring in nurse leaders in CEE. When the CEE and American experience are
      compared using these dimensions, nurse leaders have far more in common, despite
      the cultural differences.

PMID- 15446608
TI  - Demographic survey of Filipino American nurses.
AB  - BACKGROUND AND OBJECTIVE: Recruitment of nurses trained in the Philippines is one
      strategy employed by US hospitals to increase our nursing workforce. As well,
      some Filipino American nurses obtained their nursing education in US schools. The
      objective of our study was to describe demographics, years of practice, work
      status, educational background, job satisfaction, and years to retirement of a
      sample of Filipino American nurses. METHODS: A nonexperimental descriptive study
      was conducted utilizing a convenience sample of 327 Filipino American nurses.
      RESULTS: Filipino American nurses were primarily educated in the Philippines,
      held BSNs, worked full time, had high job satisfaction, and planned to retire, on
      average, in 12 years. CONCLUSIONS: The retirement plans of Filipino American
      nurses recruited to US hospitals during past workforce shortages forecast
      vacancies of nurses who have consistently worked full time and report high job
      satisfaction. Current workforce stakeholders should be alerted to these nurses'
      plans.

PMID- 15446609
TI  - Diversity: creating an environment of inclusiveness.
AB  - Diversity is a concept that most organizations espouse but find challenging to
      put into practice. It is especially critical for healthcare organizations to be
      responsive in addressing issues of diversity related to not only employees but
      also clients. This article identifies the following 3 areas that must be
      addressed if an organization is to succeed in creating an environment where
      diversity and inclusiveness are honored: (1) organizations and their leaders need
      to be aware of their reactions "those who are different" in their organization.
      This awareness is critical in identifying the underlying obstacles that prevent a
      truly inclusive workplace; (2) organizations and their leaders need to be able to
      expand their perspectives allowing them to not only understand but appreciate
      others. These expanded perspectives can provide a potentially powerful tool for
      both problem solving and conflict resolution; (3) if organizations and their
      leaders are actively engaged in exploring options and are open to alternatives,
      they will find that they not only succeed in creating an environment of
      inclusiveness but also are in a better position to meet the needs of employees,
      patients, and a multicultural society.

PMID- 15446610
TI  - Light at the end of the tunnel: a vision for an empowered nursing profession
      across the continuum of care.
AB  - Lacking political stewardship, healthcare in America is shaped primarily by
      rapidly changing market forces seeking to stem the tide of rising healthcare
      costs. However, nursing's voice in this process is fragmented and unfocused.
      Staff nurses' focus and commitment are to quality care rendered at the bedside
      and in interactions with the patient. With this narrow focus, staff nurses are
      paralyzed by the constant change and unable to move to a broader, more
      integrative view of healthcare-one that encompasses quality care, policymaking,
      and healthcare finance. Using the theory of transformative learning, nurse
      administrators and managers can influence nurses' frames of reference and expand
      their view to be more inclusive. Nurses who are successful in this transformation
      process will emerge with a new view of self-visible and empowered. These newly
      transformed nurses see themselves more as healthcare engineers than as
      technicians coordinating care across the continuum, and creating fluid working
      relationships to prevent the dis-continuum of care of patients falling through
      the cracks of the current healthcare system.

PMID- 15446611
TI  - Recruit, retain, assess: technology's role in diversity.
AB  - With the worsening nursing shortage and increasingly diverse patient population,
      nursing can no longer afford to maintain its traditional homogeneity. This
      article will discuss how information technology is playing and can play a role in
      recruiting, retaining, and assessing diversity in nursing.

PMID- 15446612
TI  - Influence of interpretive styles of stress resiliency on registered nurse
      empowerment.
AB  - The purpose of this predictive, nonexperimental study was to describe the
      influence of 3 interpretive styles of stress resiliency on phychological
      empowerment; psychological empowerment has been identified as a primary predictor
      of RN job satisfaction. Subjects were 142 nurses, randomly selected from 4 unit
      in 2 hospitals in a mid-Atlantic state. Measures used were Spreitzer's
      questionnaire for psychological empowerment (Chronbach alpha for this study =
      .89) and Thomas and Tymon's Stress Resiliency Profile for interpretive styles
      (Chronbach alpha for this study = .87, .74, and .85, for deficiency focusing,
      necessitating, and skill recognition, respectively). Regression analysis
      identified a model predictive of psychological empowerment in which 24% of the
      variance was explained by skill recognition and deficiency focusing components of
      interpretive styles, suggesting that nurses who believe they are effective and
      who do not imagine their own failure add to their own empowerment.

PMID- 15446613
TI  - Geographic information systems in public health and medicine.
AB  - Geographic information systems (GIS) are increasingly being used in public health
      and medicine. Advances in computer technology, the encouragement of its use by
      the federal government, and the wide availability of academic and commercial
      courses on GIS are responsible for its growth. Some view GIS as only a tool for
      spatial research and policy analysis, while others believe it is part of a larger
      emerging new science including geography, cartography, geodesy, and remote
      sensing. The specific advantages and problems of GIS are discussed. The greatest
      potential of GIS is its ability to clearly show the results of complex analyses
      through maps. Problems in using GIS include its costs, the need to adequately
      train staff, the use of appropriate spatial units, and the risk it poses to
      violating patient confidentiality. Lastly, the fourteen articles in this special
      issue devoted to GIS are introduced and briefly discussed.

PMID- 15446614
TI  - Analyzing geographic patterns of disease incidence: rates of late-stage
      colorectal cancer in Iowa.
AB  - This study, using geocodes of the locations of residence of newly diagnosed
      colorectal cancer patients from the Iowa Cancer Registry, computed continuous
      spatial patterns of late-stage rates of colorectal cancer in Iowa. Variations in
      rates in intrahospital service regions were as great as interhospital service
      regions, shown by analysis of variance tests. Some of the spatial variations
      observed could be explained, using a general linear regression model on
      individual-level data, by spatial variations in attributes of individuals and
      their relationships to health resources. We show how this source of variation can
      be removed from the original map leaving a new map showing the remaining
      variation in late-stage rate not explained by these relationships. We argue that
      it would be more appropriate to organize prevention and control activities
      targeted at the areas with higher than expected late-stage rates shown on this
      map. The originality of this approach is in the integration of geocoded data from
      a cancer registry with methods of spatial analysis that provide considerable
      geographic detail in the cancer rate while controlling for rate stabilization and
      reliability due to the small number problem.

PMID- 15446615
TI  - Spatial clusters of cancers in Illinois 1986-2000.
AB  - Elevated cancer rates in some areas may arise simply by chance. The pattern
      generally warrants a study only when it is statistically significant. This
      research uses a recently developed spatial statistic, implemented in a Geographic
      Information System (GIS) environment, to detect spatial clusters of
      diagnostically specific cancers in Illinois. On the basis of the cancer incidence
      data (the 1986-1990 and 1996-2000 data sets) from the Illinois Cancer Registry,
      the study examines different clustering patterns of four leading types of cancer
      in Illinois, namely breast, lung, colorectal, and prostate cancers. The first
      part of the study uses the data at the county level, and the second part uses the
      data in zip code areas. The analysis using the zip code area data directly may be
      problematic since the rate estimates for rare events like cancer in small
      populations are susceptible to data errors. The spatial order method is used to
      group zip code areas so that the new geographic areas have sufficiently large
      base populations for estimates of reliable cancer rates. Results from the spatial
      cluster analysis may be valuable for other researchers to design follow-up case
      control and retrospective cohort studies.

PMID- 15446616
TI  - Using GIS in government: an overview of the VHA's Healthcare Atlas, FY-2000.
AB  - The amount of VA data available for analysis can be overwhelming to individuals
      who need to translate these data into usable information. The Atlas, using
      current GIS technology, was funded to provide data in a comprehensive guide.
      Patients were identified using a disease classification scheme based on Kaiser
      Permanente methodology and the Clinical Classifications Software (AHRQ).
      Utilization data were extracted from the Medical SAS Datasets. Cost data were
      obtained from the HERC. GIS tools were used to create the Atlas. The Atlas
      overviews the location of VA hospitals; profiles veteran, VA enrollee and patient
      populations; examines overall utilization; depicts patterns in healthcare use by
      specific disease cohorts; and examines geographic variations in costs. This
      product will enhance knowledge of VA's enrolled patient population and their
      healthcare needs, and provide background information that will improve the
      formulation of specific research questions to address those needs.

PMID- 15446617
TI  - Using GIS to profile health-care costs of VA Quality-Enhancement Research
      Initiative diseases.
AB  - The Health Services Research and Development (HSR&D) Service at the Department of
      Veterans Affairs (VA) Health Care System launched a Quality Enhancement Research
      Initiative (QUERI) in 1998. This study estimated health-care costs of nine
      diseases under the QUERI project and analyzed geographic differences in health
      care costs and utilization across 22 VA Integrated Service Networks (VISNs),
      using a geographic information system (GIS). Patients with these diseases were
      identified from diagnoses recorded between October 1999 and September 2000.
      Annual health-care costs for each disease were estimated in four categories:
      inpatient medical or surgical, other inpatient, outpatient, and outpatient
      pharmacy. Geographic differences of costs and health-care utilization across the
      22 VISNs for chronic heart failure, diabetes, and spinal-cord injury were mapped
      using a GIS package. Average costs and patterns of health-care utilization varied
      substantially across the 22 VISNs. The observed differences in health-care
      utilization across geographic regions raised questions for further investigation.

PMID- 15446618
TI  - Temporal changes of access to primary health care in Illinois (1990-2000) and
      policy implications.
AB  - This paper examines temporal changes of access to primary health care in Illinois
      between 1990 and 2000 in a Geographic Information System (GIS) environment.
      Census data at the census tract level in 1990 and 2000 were used to define the
      population (demand) distribution and related socioeconomic attributes, and the
      Physician Masterfile of American Medical Association in corresponding years was
      used to define the physician (supply) distribution at the zip code level. A two
      step floating catchment method was employed to measure the spatial access,
      considering locations of physicians and population and travel times between them.
      Various socioeconomic and demographic variables were consolidated into three
      factors (i.e., socioeconomic disadvantages, sociocultural barriers, and high
      healthcare needs) for measuring the nonspatial access. Spatial and nonspatial
      factors were finally integrated together to assess the primary care physician
      shortage areas. The study shows that spatial accessibility to primary care
      physician for the majority of the state improved from 1990 to 2000. Areas with
      worsened spatial accessibility were primarily concentrated in rural areas and
      some limited pockets in urban areas. The worst among these worsened areas
      appeared to be associated with populations with high scores of socioeconomically
      disadvantages, sociocultural barriers, and healthcare needs. Improving the
      accessibility of those socioeconomically disadvantaged population groups is
      critical for the success of future policies.

PMID- 15446619
TI  - Access to community pharmacies by the elderly in Illinois: a geographic
      information systems analysis.
AB  - Community pharmacies play an important role in maintaining population health in
      the United States. They are large in number, distribute widely across geographic
      areas, and operate for long hours. Because the elderly population tends to use
      more medications and have more frequent interaction with pharmacies and
      pharmacists, this study was carried out to understand the geographic access to
      community pharmacies by the elderly in Illinois and to estimate the disparity in
      the access between rural and urban areas. The addresses of all community
      pharmacies operating in 2001 were geocoded to identify their locations. The
      Census 2000 data on demographics at the census block group level was used to
      estimate the geographic distribution of the Illinois population by age group.
      Using the centroid of each census block group and the locations of community
      pharmacies, the distance to a nearest pharmacy for each census block group was
      calculated. The distance was then weighted to compute the aggregated distance
      required for the elderly to access a pharmacy. There were 1373 community
      pharmacies operating in Illinois in 2001. Most pharmacies (93.8%) were located in
      urban areas. On average, there were 1.27 and 0.38 pharmacies per 10,000 people in
      urban and rural areas, respectively. The average distance for an elderly person
      in Illinois to locate a community pharmacy was 0.9 miles in urban areas, but it
      was six times more (5.9 miles) in rural areas. At least 10% of the rural elderly
      had to travel more than 11.8 miles to find a community pharmacy, but only 0.1%
      had to travel more than 20 miles. The geographic access to community pharmacies
      appears to be appropriate in Illinois. However, a small portion of rural elderly
      who do not have a pharmacy in their nearby areas may warrant special attention.

PMID- 15446620
TI  - Using GIS to monitor emergency room use in a large urban hospital in Chicago.
AB  - Geographic Information System (GIS) technology is being used at Mount Sinai
      Hospital in Chicago to better understand utilization patterns by the city's fire
      department and the subsequent effects on the rates of trauma cases who leave
      without being treated (LWOT) and throughput times. In this process, opportunities
      for process improvement in data capture, categorization, and analysis are being
      realized. Further, to more intelligently apply resources, a surge protocol has
      been developed calling for deploying physician assistants, which is having a
      positive effect on throughput times and LWOT rates. Finally, opportunities for
      GIS application in urban mass casualty planning are offered for consideration.

PMID- 15446621
TI  - Prenatal care need and access: a GIS analysis.
AB  - Many municipalities provide special prenatal care services targeted to low-income
      women whose access to prenatal care is constrained. For such services to be
      successful and effective, they must be geographically targeted to the places
      where low-income, high-need mothers live. This paper presents a GIS analysis of
      prenatal care need and clinic services for low-income mothers in Brooklyn, NY. We
      analyze fine-grained geographic variation in need using data on the residential
      locations of recent mothers who lack health insurance or are covered by Medicaid.
      Spatial statistical methods are used to create spatially smoothed maps of the
      density of mothers and corresponding maps of the density of prenatal clinics. For
      these mothers, clinic density is positively associated with early initiation of
      prenatal care. Although clinic locations conform relatively well to the
      residential concentrations of high-need women, we identify several underserved
      areas with large numbers of needy women and few clinics available.

PMID- 15446622
TI  - Sex differences in perceived importance of hamstring stretching among high school
      athletes.
AB  - Adolescent athletes completed a hamstring stretching technique and opinion survey
      and were measured for hamstring extensibility during preparticipation
      examination. Hamstring muscle group stretching practices, extensibility, and
      perception of importance to injury prevention, athletic performance, warming-up,
      cooling down, and coaches were contrasted by sex. As expected, girls displayed
      greater hamstring muscle group flexibility than boys. Boys and girls reported
      similar hamstring stretch repetitions and stretch duration. Boys scored hamstring
      stretching as being more important to improved athletic performance and to their
      coaches than did girls. Differences were not evident between groups for
      prevention of injury, warm-up, or cool-down. The lower perception of hamstring
      stretching importance for improving athletic performance and a lesser perception
      of hamstring stretching importance to their coaches suggests that adolescent
      female athletes and their coaches may not fully understand the value of static
      hamstring stretching. Modified hamstring stretching technique may selectively
      increase hamstring extensibility among girls without contributing to increasing
      capsuloligamentous knee joint laxity.

PMID- 15446623
TI  - Relationships between recovery-stress state and performance in sprinters and
      jumpers.
AB  - This study investigated the possible relationship between recovery-stress state
      and competition results in sprinters and jumpers. The Recovery-Stress
      Questionnaire for Athletes of Kellmann and Kallus was used. The subjects were
      tested one day before the Estonian Indoor Championships (n = 10; 4 men and 6
      women) and Outdoor Championships (n= 11; 4 men and 7 women). The competition
      results were measured as International Amateur Athletic Federation points. Scores
      for Fatigue (r = -.74) and Emotional Stress (r =-.79) from the subscales were
      correlated with IAAF points during Indoor Championships. Competition results from
      the Outdoor Championships were correlated with scores on the Somatic Complaints
      (r =-.70) and General Well-being (r = .63) subscales. Individual analysis
      suggests a possible relationship between the recovery-stress state and
      performance in competition which should be investigated further.

PMID- 15446624
TI  - Seasonality of suicide in Eastern Europe: a rejoinder to Lester and Moksony .
AB  - Seasonality of suicide in Hungary decreased from the 1980s to the 1990s,
      supporting the 2003 conclusion of Lester and Moksony. However, it was the
      strongest ever to be documented with contemporary suicide data, supporting the
      conjecture of Voracek, et al. (2002) that seasonality of suicide remains high in
      Eastern Europe. A new hypothesis regarding the co-occurrence of high incidence
      and strong seasonality of suicide is presented.

PMID- 15446625
TI  - Response preparation and stimulus-response congruence to fractionating reaction
      time of upper and lower limbs.
AB  - We measured the fractionating reaction time for upper and lower limbs of 18 young
      men, using an electromyogram to clarify the interaction of response preparation
      and stimulus-response congruence on premotor and motor time. The reaction time
      was divided into two periods with respect to the onset of the electromyogram,
      premotor and motor components. Manipulating the probability of the Go versus NoGo
      signals varied three different amounts of response preparation. Prior to the
      imperative stimulus, precue information about the position of a stimulus was
      presented. In the stimulus-response congruent task, subjects were required to
      release a key on the same side of the body using either an upper or lower limb in
      response to an imperative Go stimulus. In the stimulus-response incongruent task,
      subjects were required to act in a reverse manner. Subjects were not supposed to
      respond to the NoGo stimulus. The premotor time of the upper and lower limb
      responses was affected by the respective effects of response preparation and
      stimulus-response congruence. The motor time of the upper and lower limb
      responses increased as the probability of the Go signal decreased but not in
      relation to stimulus-response congruence. These results suggest that response
      preparation affects not only information processing time but also peripheral
      motor activity due to motor programming, and that the stimulus-response
      congruence effect on motor time disappears when information about the position of
      the imperative stimulus is precued.

PMID- 15446626
TI  - Reaching long-term goals based on local interaction between an organism and the
      environment: computer simulations based on adaptive behavior.
AB  - An agent-based computer simulation created using the adaptive-behavior approach
      has shown that in some cases it is possible to reach a long-term goal (defined
      here as a desirable place far removed from the agent in time and in space)
      without necessarily having an exhaustive, predefined plan of action, but rather
      by using a set of rules on sensorimotor couplings that govern the organism's
      local interaction with its environment. We used an agent-based simulation program
      that emulated a two-dimensional microworld in which agents interacted with their
      environment and other agents through a set of sensorimotor couplings to reach a
      long-term goal. The main hypothesis was that the sensorimotor coupling, which
      consisted of following other agents, led to the emergence of collective behavior
      that enabled the agents to attain the long-term goal. We systematically varied
      the sensorimotor couplings that allowed agents to follow other agents, agents'
      perceptual field length, and the number of obstacles. In total, there were 160
      independent simulations for each design cell. Analysis supported the hypothesis
      and suggested that, in addition to the process of reaching long-term goals, other
      cognitive processes, such as categorization, memory, and reasoning, can be
      reconsidered bearing in mind the emergence of behavior and an approach based on
      interaction between the organism and its environment.

PMID- 15446627
TI  - Sound level of background music and alcohol consumption: an empirical evaluation.
AB  - The effect of background music on alcohol consumption has been widely researched
      in the literature, but few studies have tested the effect of sound level on
      drinking behavior. An experiment was carried out in two bars to test patrons'
      response to music's loudness. Using random assignment, patrons were exposed to a
      sound level which was higher than that usually employed in the bars in which the
      study took place. Analysis showed that a higher sound level than usual was
      associated with consuming more drinks. An "arousal" hypothesis is used to explain
      the findings.

PMID- 15446628
TI  - Young girls' developmental skills in underarm throwing.
AB  - This paper concerns underarm throwing by girls 7 to 12 years of age. Each
      movement component by trained and untrained girls in underarm throwing or
      windmill softball pitching was examined. Movement characteristics of ball
      release, arm motion, trunk activity, and stepping were analyzed to capture
      experience- and age-related differences in underarm throwing. A total of 48 young
      girls participated: 25 untrained (age 9.7 yr.), 14 trained/league (age 10.9 yr.),
      and 9 trained/formal (10.4 yr.). Performance was videotaped individually and
      evaluated by three observers. Analyses suggest that, while age did not affect
      performance, the type of training experience influenced the girls' performance on
      each of the four movement components. The wrist and trunk were identified as
      showing the most significant progression with experience. The findings have
      important implications about changes during acquisition of underarm throwing
      skills.

PMID- 15446629
TI  - Association of exercise counselors' sex with exercise session attendance in women
      enrolled in a cognitive behavioral treatment system.
AB  - Attendance rates from two groups incorporating a cognitive behavioral treatment
      system (male counselor group, n=53; female counselor group, n=56) and a control
      group using standard methods of exercise counseling (n =56) were contrasted with
      new and returning female exercisers (overall M age=40 yr.). Analysis of variance
      with follow-up Scheffe tests indicated significantly greater attendance for the
      treatment groups (54 and 58%) than for the control group (37%) over 6 months. No
      significant difference between the treatment groups was found. Findings suggest
      that the sex of exercise counselors does not appear to influence attendance of
      exercise sessions.

PMID- 15446630
TI  - Mental and physical practice schedules in acquisition and retention of novel
      timing skills .
AB  - Research has indicated that random physical practice of a motor skill enhances
      effects of long-term learning more than blocked practice. Moreover, the use of
      mental rehearsal coupled with physical practice has been shown to accelerate
      motor skill acquisition in many different contexts and is better than no practice
      at all. Others have found that some mental rehearsal strategies are better than
      others for maximizing performance. This study examined how combinations of mental
      and physical practice schedules affected the learning of a coincidence timing
      task. 30 college students were randomly assigned to one of four treatment groups
      involving combinations of imagery and physical practice. Three tasks were
      utilized, each involving a particular speed (slow, medium, fast) on the Bassin
      Anticipation Timer. Conclusions were based on a three-way analysis of variance,
      using type of mental practice, type of physical practice, and sex as between
      group factors, conducted separately for acquisition and retention trials. Type of
      physical practice was significantly related to performance. On the acquisition
      trials, random practice was associated with larger mean errors than blocked
      practice; however, the reverse was true for retention trials. There was no
      significant effect of type of mental practice in either the acquisition or
      retention phase. Sex was significantly related to performance for the retention
      trials only, where the 15 men made smaller errors than the 15 women.

PMID- 15446631
TI  - Analysis of Kavale and Mattson's "balance beam" study (1983): criteria for
      selection of articles.
AB  - The effects of perceptual motor training in children with learning disabilities
      have been hotly debated for many years. Proponents have included many of the
      pioneers in the fields of learning disabilities and motor development. Among the
      challenges perhaps the most sophisticated one has been the meta-analysis by
      Kavale and Mattson. Their conclusion was that perceptual motor training was not
      an effective intervention for children with disabilities. The purpose of this
      project was to analyze critically the Kavale and Mattson meta-analysis from the
      perspective of an adapted physical educator and to consider the validity of this
      meta-analysis when examining multiple interventions dealing with a multitude of
      disabilities. A critical analysis of all 180 studies question their conclusions.

PMID- 15446632
TI  - Personality differences in high risk sports amateurs and instructors.
AB  - This study investigated the personality differences of 21 amateurs and 20
      instructors who participated in the high risk sports of skydiving, hang-gliding,
      paragliding, scuba diving, microlighting, and rock climbing, versus those who did
      not. 38 men and 28 women (M age=32.6 yr., SD= 10.0) were assessed using the
      Eysenck Personality Questionnaire-Revised, the General Health Questionnaire, the
      Generalised Self-efficacy Scale, and a Type A/B personality measure. Instructors
      and Amateurs scored significantly higher on Extroversion and lower on Neuroticism
      than Nonparticipants; however, they differed from each other on the General
      Health Questionnaire and Type A/B personality scores. Amateurs scored
      significantly higher on Psychoticism and Self-efficacy than Instructors and
      Nonparticipants. In conclusion, these test scores suggest that people who are
      attracted to high risk sports tend to be at the extroverted and emotionally
      stable end of the scale, with a tendency to exhibit Type A characteristics;
      however, Instructors' scores on Psychoticism and Self-efficacy are more akin to
      those of Nonparticipants.

PMID- 15446633
TI  - Bridging the divide between laboratory and "real world" in stuttering.
AB  - Stutterers stutter significantly less in the laboratory and the clinic than in
      everyday speaking situations. This paper reviews pertinent literature to show
      that, in the outside world, stutterers have a stake in what they say and
      therefore message content and interpersonal dynamics command attention-relegating
      speech-motor planning and execution to an automatic, memory-based process called
      speech concatenation. In the laboratory and the clinic, content of communication
      and interpersonal dynamics are less important, allowing stutterers to concentrate
      on the motor planning of articulation and prosody. Evidence reviewed here
      suggests that speech construction (real time preparation of an utterance motor
      plan) is incompatible with stuttering. Evidence also suggests that a slight delay
      in retrieving motor plans from memory during speech concatenation is the
      immediate source of stuttering.

PMID- 15446634
TI  - Refinement of terminology in qualitative analysis of human movement.
AB  - The emergence of qualitative analysis of human movement as a sub-discipline
      within the discipline of Kinesiology has led to a slow refinement in definitions
      and terms used to describe the area as a whole and parts of the total analysis
      process. A 2003 paper by McKethan, Kernodle, Brantz, and Fischer illustrates some
      differences in use of terminology. Using their terminology, differences are noted
      with a view to standardizing terminology in the subdiscipline.

PMID- 15446635
TI  - Relationship of feeling states after exercise and Total Mood Disturbance over 10
      weeks in formerly sedentary women.
AB  - Changes in feeling states after exercise and changes in overall mood after a
      period of 10 weeks were correlated after participation in a supervised, moderate
      intensity resistance training program. 52 previously sedentary, asymptomatic
      women (M=56 yr.) participated. Point biserial correlations were calculated
      between the 10-wk. change on the Profile of Mood States using the Total Mood
      Disturbance score as the continuous variable, and positive or negative change in
      feeling states after exercise, assessed via the Exercise-induced Feeling
      Inventory, being the dichotomous variable. Correlations were significant for both
      the total sample (rpb=-.49) and participants with high initial Total Mood
      Disturbance based on a median split (rpb=-.55). Participants with positive
      changes in their feeling states after exercise also showed a significantly
      greater decrease in Total Mood Disturbance than those with negative changes.
      Changes in Total Mood Disturbance were not significantly correlated with changes
      in resting heart rate over the 10 weeks. Discussion included limitations and,
      after replication, possible application of the findings.

PMID- 15446636
TI  - Contextual interference: a meta-analytic study.
AB  - A meta-analysis of the contextual interference effect produced 139 estimates of
      effect sizes from 61 studies. The average overall effect size was .38. The effect
      size for basic research (.57) was significantly different from applied research
      (.19). Significant differences were also obtained between the effect sizes for
      adults (.50) and those for younger learners (.10). Power for retention and
      transfer scores was not significantly different. The overall mean power of the
      studies reviewed was .43.

PMID- 15446637
TI  - Interaction between preference and instructions for a focus of attention in
      billiards.
AB  - The present study evaluated the interaction between preference for a focus of
      attention and instructions for focusing attention. 4 experienced billiard players
      had to shoot a billiard ball into a target area and received a focus instruction
      either corresponding or opposite to their preferred focus of attention. Two
      dimensional error scores of accuracy and consistency were obtained. Accuracy of
      performance increased between Phase 1 without instructions and Phase 2 with focus
      instructions, independent of preference or instruction. However, participants
      with a preference for an external focus receiving an internal focus instruction
      showed less consistent performance.

PMID- 15446638
TI  - Changes across age groups in self-choice elaboration effects on incidental
      memory.
AB  - The present study investigated age differences in the effects of a self-choice
      elaboration and an experimenter-provided elaboration on incidental memory.
      Adults, sixth grade, and second grade subjects chose which of two sentence frames
      the target fit better in a self-choice elaboration condition. They then judged
      whether each target made sense in its sentence frame in the experimenter-provided
      elaboration, then did free recall tests. Only adults recalled better the targets
      with an image sentence with self-choice elaboration, rather than experimenter
      provided elaboration. However, self-choice elaboration was far superior for the
      recall of targets with nonimage sentences only for second graders. Thus, the
      effects of self-choice elaboration were determined both by age and by type of
      sentence frame.

PMID- 15446639
TI  - Relationship of social cognitive theory factors to exercise maintenance in
      adults.
AB  - Modifiable variables related to Bandura's social cognitive theory were tested for
      their relationship to self-reported retrospective exercise maintenance in 178
      adults. Significant bivariate correlations were found between length of adherence
      to regular moderate-to-vigorous exercise and item clusters reflecting social
      support (r = .42), self-management ability (r =.39), and ability to tolerate
      exercise-induced discomfort (r = .60). Stepwise multiple regression analysis
      indicated that each item cluster significantly contributed to the overall
      explained variance in length of exercise maintenance over 52 weeks (R2 =.43).
      When responses from each of the item clusters were summed, participants defined
      as adherents had significantly higher scores than drop-outs. Discussion
      emphasized the need for replication and implications for exercise adherence
      intervention.

PMID- 15446640
TI  - Proprioceptive training for learning downhill skiing.
AB  - The aim was to assess whether balance training would improve downhill skiing for
      30 physical education students who had no previous skiing experience and were
      randomly assigned to two groups. The control group attended only ski lessons for
      two weeks, 2 to 4 hours daily. The experimental group attended downhill ski
      lessons and indoor balance training on a balance board, wearing ski boots, for 20
      min. every second day in the afternoon. All participants before training
      completed a balance assessment (stability indices). After the completion of the
      ski classes, all repeated the balance assessment and two downhill ski tests of
      agility, slalom and snow-ploughing techniques. Analysis of variance with repeated
      measures showed both groups improved balance similarly, but the experimental
      group performed significantly better on the downhill-slalom agility test, so the
      specific indoor balance training was helpful.

PMID- 15446641
TI  - Comparison of the Cognitive Styles Analysis and the Style of Processing Scale.
AB  - The Cognitive Styles Analysis and the Style of Processing Scale are two tests
      designed to assess verbal-visual cognitive style. These scales represent two of
      the main approaches to assessing verbal-visual cognitive style, namely, computer
      based testing and paper-and-pencil testing. A student sample (N=75; sex: 23 men,
      52 women; age: M= 18.1 yr., SD= 1.7 yr.) yielded low correlations between the
      verbal-visual components of the tests (largest r = .08), indicating that they are
      unlikely to be related. The Cognitive Styles Analysis has some support for
      validity but its reliability has recently been criticised. The Style of
      Processing Scale has demonstrated reliability but has little support for
      validity. Currently, neither test could be considered a dearly dependable scale
      for assessing verbal-visual cognitive style.

PMID- 15446642
TI  - Expertise and position of line of sight in golf putting.
AB  - The purpose of this study was to clarify golfers' scanning patterns while putting
      through direct measurement of their eye movements. Each of the 17 subjects (3
      experts, 3 intermediates, 11 beginners) performed 10 consecutive putts on a
      practice mat, from a position 2 m from the hole. The analysis of their eye
      movements indicated differences among these groups. The intermediates and
      beginners had longer fixation durations on the ball than the experts. The
      beginners exhibited a range of behaviors among the trials, some of which did not
      include any fixations on the ball. Experts held their eyes steady but did not
      fixate on the ball. These results suggested that experts may have relied on a
      mental image of the ball; in contrast, the intermediates and some of the
      beginners relied on visual data.

PMID- 15446643
TI  - Comparison of perceived backpack comfort using two rating scales.
AB  - Students' current use of backpacks to carry heavy loads of school material has
      promoted concern about musculoskeletal discomfort and postural problems. The
      purpose of this study was (a) to compare ratings of perceived comfort between
      subjects' personal backpacks and an experimental backpack and (b) to compare the
      data from two comfort rating scales. College-aged students (N= 19) in a random
      ordered, cross-over design rated their personal, traditional backpacks and
      experimental backpacks for perceived neck, shoulder, back, and overall comfort on
      a 100-mm Visual Analog Scale and on an Anatomical Illustration Rating Scale.
      Analysis indicated no significant difference in comfort ratings of backpacks on
      Visual Analog Scale but, on the Anatomical Illustration Rating Scale the
      experimental backpack was significantly (p<.05) more comfortable for the back.
      Further comparisons of backpacks, based on median splits of subjects' weight,
      height, and body mass index, indicated that body size is related to comfort
      ratings of backpacks. Special features of the experimental backpack may have
      contributed to greater comfort in selected areas based on body proportion.
      Subjective rating systems are not equally sensitive in distinguishing comfort.
      While backpacks with unique features may improve comfort, manufacturers should
      consider the size of the users in developing backpack designs.

PMID- 15446644
TI  - Linguistic humor comprehension in children with articulation impairments.
AB  - This study investigated the ability of children with articulation disorders to
      comprehend linguistic humor. It was hypothesized that children with articulation
      disorders would have more difficulty understanding humor based on phonological
      differences than humor based on lexical differences. A second hypothesis
      predicted that children with articulation disorders would have more difficulty
      understanding riddles in which the phoneme they misarticulated, either /s/ or
      /r/, was the source of ambiguity than riddles in which the source of ambiguity
      did not involve the phoneme they misarticulated. Results did not confirm the
      first hypothesis as there were no statistically significant differences between
      groups with regard to the children's ability to understand phonological vs
      lexical humor. The second hypothesis was supported. Children had significantly
      more difficulty understanding riddles in which the source of ambiguity related to
      the phoneme they misarticulated, either /s/ or /r/ than they did understanding
      phonological humor involving nonerror phonemes.

PMID- 15446645
TI  - Relationship between self-efficacy and changes in rated tension and depression
      for 9- to 12-yr.-old children enrolled in a 12-wk. after-school physical activity
      program.
AB  - 28 girls and 26 boys (93% African American) ages 9 to 12 years were enrolled in
      an after-school physical activity program for 12 wk. and completed measures of
      exercise self-efficacy, tension, and depression. Significant negative
      correlations were found between changes in ratings on Exercise Self-efficacy
      Scale for Children scores and Profile of Mood States Tension (r =-.44) and
      Depression (r =-.33) over 12 wk., indicating that as rated exercise Self-efficacy
      increased, rated Tension and Depression tended to decrease. Findings are
      consistent with behavioral explanations of the relationship between exercise and
      mood changes. Caution is appropriate as there was no control group, and
      familiarity might be an explanation of the findings.

PMID- 15446646
TI  - Effects of a stress-management program on injury and stress of competitive
      gymnasts.
AB  - 20 competitive gymnasts (17 girls, 3 boys; mean age, 14.4 +/- 3.4 yr.) were
      recruited from two clubs in Auckland, New Zealand. Gymnasts, who had competed at
      a national or international level, were divided into two groups to examine the
      effects of a longitudinal stress-management program on injury and stress. Those
      in the stress-management group took part in 12 1-hr. sessions over 24 weeks,
      while the control group took part in a placebo program of anthropometric
      measurements and lectures on nutrition. All participants completed the Life
      Experiences Survey and Athletic Experiences Survey at baseline, 3 mo., 6 mo. (end
      of intervention), and 9 mo. (3 mo. after completion of intervention). Injury data
      were collected prospectively by weekly self-report over the 9-mo. study. Repeated
      measures analyses of covariance with age and, where applicable, the baseline
      measure of the dependent variable entered as covariates, indicated no significant
      group or group by time effects for the scores on the two surveys, or injury
      scores. However, given the small sample, the statistical power of the study to
      detect even large effects was low. Therefore, rather than concluding that the
      stress-management program had no effect on training hours lost to injury or on
      stress, upper limits were placed on the magnitude of any effects that might
      exist. Further research using larger samples is recommended.

PMID- 15446647
TI  - Image of aging scale.
AB  - The development of the Image of Aging Scale is described. It ineludes positive
      and negative images of elders within nine domains. The scale showed good 1-wk.
      test-retest reliability, internal consistency, and convergent validity.

PMID- 15446648
TI  - Gastroesophageal reflux disease: attachment style and parental bonding.
AB  - The attachment styles and parental bonding of 72 patients (M age= 45.3 yr.,
      SD=13.5) suffering from Gastroesophageal Reflux Disease were compared with those
      of 105 healthy subjects (M age =44.9 yr., SD = 5.8). A clinical interview and two
      questionnaires, the Attachment Style Questionnaire and the Parental Bonding
      Instrument, showed that the scores on the ASQ Confidence subscale were
      significantly lower in the clinical group. Similar results were obtained for the
      Discomfort with Closeness subscale in the subsample with Pure Gastroesophageal
      Reflux Disease. The results indicate Insecure Attachment in the clinical sample.
      The results obtained from the Parental Bonding Instrument indicate that scores on
      the Protection Mother scale were significantly higher in the clinical subjects,
      suggesting a Low Care-High Protection combination (Affectiveless Control), at
      least for patients with pure Gastroesophageal Reflux Disease. These
      characteristics can be considered important factors in the tendency to
      somatization. The symptoms may have a paradoxically normalising function while
      the patient shows an emotional detachment towards intimate relationships. The
      illness appears to act as a bond through which the relationship with the
      caregivers is maintained.

PMID- 15446649
TI  - The level-style of creativity distinction: comments on a recent comparison of two
      measures of creativity style.
AB  - A recent article published in this journal made a contribution to our
      understanding of the relationships between two measures of creativity style. The
      authors interpreted their results and made a few statements that made a subtle,
      yet substantial link between the styles measured by the assessments and creative
      abilities. The purpose of this commentary is to point out a more general concern
      relating to keeping these constructs distinct and then using clear measures to
      help increase our understanding and appreciation of diverse styles of creativity
      and how they contribute to improving creative abilities. Even those researchers
      who attempt to clarify the differences can slip into using language that
      conflates style with level.

PMID- 15446650
TI  - Growth rates in running speed and vertical jumping by boys and girls ages 11-13.
AB  - This study examined growth rates in running speed and vertical jump among middle
      school children. 45 boys and 31 girls ages 11-13 years were tested on running
      speed and vertical jump three times (September, February, and May) during the
      school year. Hierarchical linear modeling was used to estimate initial status and
      growth rates for the entire sample (base model) and the association of running
      and vertical jump with height, weight, and sex (conditional model). Positive
      overall growth rates were found for both running speed and vertical jump.
      Increased heightand weight at the time of measurement were not significantly
      associated with growth rate for running. The growth rate for vertical jump was
      positively associated with height but unrelated to increased weight. Boys showed
      steeper growth rates than girls in jumping. No sex differences were found in
      running speed for either initial status or in growth rate. Furthermore, these
      results suggest highly variable rates of physical maturation but no general
      period of 'adolescent awkwardness'.

PMID- 15446651
TI  - Visual analogue scale correlates of musculoskeletal fatigue.
AB  - Visual analogue scale has been shown to reflect subjective feelings but rarely
      has it been used for musculoskeletal fatigue so in the present study VAS ratings
      were used to quantify musculoskeletal fatigue. A total of 20 students underwent a
      fatigue protocol (M age=21.3 yr., SD= 1.0). A series of randomized external loads
      at 0, 5, 10, 15, 25, 35, and 50% of the maximum voluntary contraction was
      generated by the BTE Primus and applied at the distal end of the dominant arm,
      which was sustained at the 90 degrees forward flexion position. After 60 sec. of
      force exertion for each loading, the subject marked the scale to reflect their
      extent of fatigue at the shoulder muscle. Analysis showed fatigue scores were
      significantly correlated with the percentages of maximum load applied (r =.73, p
      < or = .01). The correlation between higher external loads (25-50% maximum load)
      and fatigue scores was .57 (p < or = .01) and that for lower external loads (0
      15% maximum load) was .44 (p < or = .01). The validity of using a visual analogue
      scale as a measure of musculoskeletal fatigue requires further study,
      particularly for a low load.

PMID- 15446652
TI  - A foot-pointing task and spatiotemporal gait parameters during walking in
      sportsmen.
AB  - Unlike many sports, karate imposes pointing to a target with the lower limb. The
      nature of each sport could influence gait variables of sportsmen. The aim of this
      study was to examine the pointing accuracy of limb swing and the spatial and
      temporal parameters of the walking cycle during walking in karate experts (Group
      K, n=6) compared to accuracy of nonkarate sportsmen (Group S, n = 11). The second
      aim of this study was to compare the influence of this skill on the spatial and
      temporal parameters of the walking cycle between the two groups. The analysis was
      performed with a device composed of a gait analysis system (locometer) coupled to
      a lighted walkway. This system provides a measurement of the motor skill and the
      spatial and temporal gait during walking. Analysis for the pointing task
      indicated no differences between the Karate and the Sportsmen Groups during
      walking. Moreover, neither the spatial nor temporal characteristics of walking
      differed between the two groups. Karate does not therefore seem to develop motor
      programs specific to enhanced performance on this pointing task during walking or
      alter the walking cycle as compared to some other competitive sports.

PMID- 15446653
TI  - Body satisfaction in adolescent boys and girls: associations with parental
      behavior.
AB  - In a sample of 449 high school students, maternal smoking and maternal and
      paternal eating habits were significantly related to self-reported Body
      Satisfaction for girls, as measured by the Body Shape Questionnaire of Cooper,
      Taylor, Cooper, and Fairburn. However, only paternal eating habits were
      significantly related to self-reported Body Satisfaction for boys.

PMID- 15446654
TI  - Test-retest reliability of the seated Functional Rotation Test in people with
      Parkinson's disease: a preliminary study.
AB  - This study established the test-retest reliability of a seated Functional
      Rotation Test monitoring hand-pointing, together with head and trunk-rotation
      performance, in people with Parkinson's disease. An ancillary purpose was to
      establish the concurrent validity between the Functional Rotation Test and an
      electrogoniometer. 10 males with Parkinson's disease (M age=70.5 yr.; Hoehn and
      Yahr staging severity ranging from II to IV) were recruited. Subjects were fitted
      with laser-pointing devices, sat in the Functional Rotation room, and were
      instructed to turn actively and point to their right (or left) as far as they
      could comfortably manage. Tagged projections were scored (in degrees). Testing
      was repeated after a brief interval. Electrogoniometer projected locations were
      compared with Functional Rotation Test scores. Intraclass correlation
      coefficients (.91 to .97) indicated excellent test-retest reliability. There was
      also excellent agreement between electrogoniometric and Functional Rotation Test
      values (Intraclass correlation coefficients=.99). Thus the Functional Rotation
      Test provides a replicable measure of axial rotation of head, trunk, and hand
      pointing in seated subjects with Parkinson's disease.

PMID- 15446655
TI  - Goal orientations, motivational climate, equality, and discipline of Spanish
      physical education students.
AB  - This study analyzes how dispositional goal orientations and perception of
      different motivational climates are related to the students' perception of sex
      related egalitarian treatment and the appearance of disciplined or undisciplined
      behaviors in physical education classes. Analyses showed that ego orientation is
      a predictor of undisciplined behavior. Task orientation was positively associated
      to discipline. The perception of task-involving motivational climate is related
      to the students' perception of equal treatment. On the contrary, the perception
      of ego-involving climate has been linked positively to the prediction of the
      perception of sex discrimination in physical education classes and negatively to
      the perception of equality and the appearance of disciplined behavior. This study
      discusses the implications of these results related to teaching instructional
      actions in physical education classes.

PMID- 15446656
TI  - Survey of advantages obtained by judoka in competition by level of practice.
AB  - In judo, placing the opponent in a situation of uncertainty requires the mastery
      of several throws. French young judoka learn, respectively, 10, 9, and 8 throws
      to earn yellow, orange, and green belts. These techniques allow throwing down a
      judoka in several directions (backward, forward, left and right). To see what
      happens in competition 82 judoka were observed during regional competitions. The
      average number of matches was 3.3 +/- 0.5. The average number of successful
      attack directions was 2.8 +/- 1.3 for 8 children at orange to green belt level;
      2.1 +/- 0.7 for 11 children at blue belt level; 2.2 +/- 0.8 for 17 children at
      brown belt level; 2.8 +/- 0.9 for 20 cadets at brown to black belt level, 2.6 +/-
      1.1 for 10 juniors at brown to black belt level, and 3.3 +/- 0.9 for 16 seniors
      at black belt level. These scores for children with blue and brown belts were
      significantly different (p=.02) from those of seniors with black belts. Such
      results imply a nonlinear progression between the technical level (represented by
      the belt) and the capacity to create uncertainty (the ability to throw down the
      opponent with at least three techniques in three different directions). Judo is a
      sport of slow technical maturation; it requires this adaptation before its
      mastery in competition.

PMID- 15446657
TI  - Control of lateral weight-transfer initiation during sitting.
AB  - Whereas many researchers have examined the transition from quiet posture to
      dynamic state, study of the initiation of lateral weight-transfer during sitting
      has only begun recently. This action is included in many tasks performed in our
      daily living, i.e., reaching, dressing, looking backwards, lying down, and
      shuffling the buttocks. The present study was designed to describe lateral weight
      transfer movements of healthy adults, kinematically and kinetically, and to
      clarify the strategies and speed dependency of lateral weight-transfer initiation
      during sitting. Seven healthy Japanese male students without orthopaedic or
      neurological disorders participated. Their lateral weight-transfer movements were
      measured during sitting, using two force platforms and a 3-dimensional analysis
      system. Analysis showed that there appear to be two strategies for the initiation
      of the task: one is the lateral bending of trunk toward the weight-transfer side,
      and the other is a coordinated reciprocal leg action of both legs. A combination
      of these strategies is used in a trade-off fashion during natural motions. These
      results are clinically important for the assessment and therapy of patients with
      sitting problems.

PMID- 15446658
TI  - Picture-name priming in the cerebral hemispheres: evidence for phonological
      access in the right hemisphere.
AB  - This study investigated right hemisphere involvement in access to phonology,
      using a picture-naming priming paradigm where pictures and names of common
      objects printed in Japanese Kana were presented in succession to the same visual
      field or different visual fields with a stimulus onset asynchrony of 250 msec. A
      naming task was used for this purpose. The result showed that, when primes and
      targets were presented to the same visual field, facilitation for related pairs
      was observed in each hemisphere, with overall naming latencies being slower in
      the right hemisphere than in the left hemisphere. This result indicates that the
      prior access to phonology for a picture in the right hemisphere facilitates
      phonological activation of a word that names the picture in this hemisphere,
      suggesting that the right hemisphere is involved in access to phonology. On the
      other hand, when primes and targets were presented to different visual fields,
      there was no facilitation for related pairs with inhibition for unrelated pairs,
      irrespective of prime and target visual fields. It is suggested that this
      inhibition-dominant pattern of priming may occur due to homotopic inhibition
      processes proposed by N. D. Cook.

PMID- 15446659
TI  - Conscious and effortful or effortless and automatic: a practice/performance
      paradox in motor learning.
AB  - High cognitive effort has been frequently related to better indices of motor
      learning through the study of many different paradigms. However, automaticity
      presumably invokes minimal cognitive processing but has often been related to
      high-level motor performance, which suggests a paradox. The objective of this
      study was to approach this paradox by examining the viability of the use of
      different cognitive strategies during practice and performance which promote the
      benefits of high cognitive effort and automaticity. Members of the university
      community (14 men and 15 women) divided into 3 groups practiced a discrete
      precision task. All participants completed four sessions totaling 320 trials and
      were tested on retention and transfer seven days later. Findings suggest that it
      is indeed possible to benefit from both effortful and minimal cognitive
      processing strategies and that they should be used complementarily.

PMID- 15446660
TI  - Faulty Japanese sentences are judged more grammatical when punctuation is used:
      negative implications for Chomsky's principle of Full Interpretation.
AB  - 88 adult Japanese speakers judged the grammaticality of isolated simple
      bitransitive sentences involving an uninterpretable extra argument in addition to
      three legitimate arguments. The sentences thus violated Chomsky's principle of
      Full Interpretation which prohibits the structure building of a sentence
      including uninterpretable elements. The primary variable of interest was the
      presence or absence of punctuation, i.e., commas, which enclosed the extra
      argument. Findings showed that sentences with punctuation were judged more
      grammatical than the ones without punctuation, with an average score of judged
      grammaticality exceeding 3 on a 7-point scale (1 =least grammatical; 7=most
      grammatical). This score would not be expected if the speakers possess and judge
      the sentences in conformity with the principle of Full Interpretation.

PMID- 15446661
TI  - Self-reported comfort in athletic training to same- and opposite-sex athletes.
AB  - To assess the comfort of athletic trainers in providing care to athletes of the
      same- and opposite-sex, the Gender Comfort in Athletic Training Questionnaire was
      developed. Cronbach alpha was .72. The 8-item questionnaire was mailed to 235
      participants, who were senior athletic training students and clinical instructors
      affiliated with 14 university athletic training programs. 192 questionnaires were
      returned (82%). Only one t test showed a significant mean difference in reported
      comfort between women (n= 103, M=2.8, SD= 0.8; disagree) and men (n= 89, M=3.1,
      SD=0.8; neutral) on the statement: I feel more comfortable providing athletic
      training services to male athletes than female athletes. The women and men in
      this sample were similar in their self-ratings of comfort in providing athletic
      training services to male and female athletes.

PMID- 15446662
TI  - Mood changes after maximal exercise testing in subjects with symptoms of exercise
      dependence.
AB  - Considering exercise has positive and negative reinforcing properties, the mood
      states of sedentary, nonexercise-dependent and exercise-dependent volunteers were
      compared after maximal exercise testing. Mood status was evaluated by the Beck
      Depression Inventory, Trait-State Anxiety Inventory, and Profile of Mood States
      (POMS). No differences were detected before the test or after it, indicating
      little possibility of positive reinforcement. However, a significant reduction in
      the POMS Tension-Anxiety scores was observed in both exerciser groups (greater in
      the exercise-dependent group) but not in the sedentary group. Only in the
      exercise-dependent group were significant reductions in Anger and Total Mood
      Disorders scores observed compared with their pre-exercise scores. These data
      suggest that exercising has stronger negative reinforcement properties for
      exercise-dependent volunteers and is a factor which could increase the odds of
      their becoming dependent on exercise.

PMID- 15446663
TI  - The formal pace of Sesame Street over 26 years.
AB  - Television producers often use a high rate in the succession of visual and
      auditory features in their programs to attract the attention of viewers. In this
      study an attempt was made to measure the formal pace of television programs by
      scoring the rates of an extensive set of formal visual and auditory
      characteristics. Sesame Street was chosen as a focal point because this
      educational program--with its high pace--is very successful in its competition
      with the majority of commercial programs from which children can choose to watch
      at home. The analyzed material consisted of 49 Dutch episodes of Sesame Street
      broadcast between 1977 and 2003. The formal pace characteristics of separate
      program items from Sesame Street could be reliably established. Factor analysis
      indicated that clear pace factors were (a) "editing," consisting of a frequent
      use of different types of shots (total shots, medium shots, and close-ups)
      combined with a large number of cuts and (b) speech rate. Over a period of 26
      years, the pace of editing increased: the mean number of cuts increased from
      about 4 to 8 per minute. The mean speech rate decreased from 175 to 139 words per
      minute.

PMID- 15446664
TI  - Effects of familiar and unfamiliar asynchronous music on treadmill walking
      endurance.
AB  - To assess effects of familiarity of music on treadmill endurance, 15 female
      undergraduates in sports science performed an incremental treadmill walking task
      on three separate occasions while listening to Familiar Music, Unfamiliar Music,
      and White Noise. A repeated-measures analysis of variance indicated that
      participants walked for significantly longer when accompanied by Familiar and
      Unfamiliar Music in comparison to White Noise (p<.01). Although participants
      rated Familiar Music as significantly more motivating than Unfamiliar music
      (p<.05), no significant differences were found between the two music conditions
      for treadmill endurance. Heart rates did not appear to be influenced by music
      during treadmill walking or on completion of the task.

PMID- 15446665
TI  - Single-digit multiplication: is there an age-of-acquisition effect?
AB  - Evidence for 37 12-yr-old students is presented which suggests that an age-of
      acquisition effect may be present in the performance of single-digit
      multiplication facts.

PMID- 15446666
TI  - [Effect of a life review process to improve quality of life for the homebound
      elderly in Japan].
AB  - OBJECTIVE: This study examined the therapeutic effects of Life Review processes
      on physical and psychological functions of homebound elderly in Japan. METHODS:
      From 1998, a cohort of people aged 65 and over living in two cities in Yamagata
      Prefecture has been followed. Sixty-three subjects (24 men, 39 women) were
      classified as rank A (homebound). Fifty-two persons completed the baseline survey
      in 1999 and 46 eligible persons (18 men and 28 women) were allocated to
      intervention and control groups whose age and sex distribution were matched.
      Intervention entailed giving some health information and Life Review processing
      for four months, twice a month on average. Each session started with provision of
      health information followed by the Life Review process which took an hour to
      finish. All subjects of both groups were assessed for dependent variables at the
      beginning and the end of the intervention period (pretest and post-test).
      Dependent variables were physical (Activities of Daily Living, Visual deficit,
      and others), psychological (subjective health, life satisfaction, self-efficacy
      scale, and others), and social (functional ability and frequency of getting out
      of the house). The control group received only the pretest and the post-test.
      RESULTS: Pretest scores for all physical, psychological, and social variables did
      not significantly differ between the two groups. The rate for improvement/no
      change were higher with regard to hearing deficit, ADL (eating, dressing),
      cognition, subjective health, ikigai and frequency of getting out of house in the
      intervention group than in the control group, but there were no significant
      differences. CONCLUSION: The developed intervention program featuring delivery of
      health information and structured Life Review Process had no negative influence
      on physical and psycho-social functions. Practicability of the intervention was
      suggested. But the study highlights problems such as selection of subjects,
      duration and method of intervention.

PMID- 15446667
TI  - [Correlation of health condition, physique and dietary-lifestyle of first grade
      and sixth grade primary school children and their mothers].
AB  - PURPOSE: Health condition, physique and dietary-lifestyle were studied by grade
      and sex of primary school children and by age, employment status, and family
      composition of their mothers. Correlation between the school children and their
      mothers were analyzed with the aim of elucidating parameters for effective health
      education. METHODS: The study was made using 2,162 first (6-7 years old) and
      sixth grade (11-12 years old) primary school children and their mothers, with
      correlation made for 1,993 cases who responded. Comparison were made by grade and
      sex of the school children and by age, employment status, and family composition
      of their mothers. For the correlation of health condition and dietary-lifestyle
      of children and mothers, a multiple logistic regression analysis was conducted.
      RESULTS: 1. Among sixth grade girls and mothers, the proportion of those who were
      lean was high, but correlation between the health condition of the children and
      physique of the children or their mothers was rated. A difference by grade and
      sex of primary school children was observed in complaints with regard to health
      condition, like cephalgia and abdominal pain in sixth grade girls. 2. It was
      found that children belonging to nuclear families whose mothers were less than 40
      years of age and were employed did not take breakfast and that among the their
      generation children whose mothers were older than 40 years and with or without
      employment the proportion whose health condition was poor and who spent more than
      3 hours a day watching television was high. 3. The results of multiple logistic
      regression analysis demonstrated that correlation among poor health condition of
      children and an irregular life rhythm, dislike for certain items of foods, no
      conversation at meal time, unpleasant meal time, insufficient mastication and
      skipping breakfast, while for poor health condition, sleep deficit, not consider
      combination of foods and unpleasant meal time on mothers. CONCLUSIONS: It was
      ascertained for the first time that were important in good health condition of
      children correlate regular life rhythm and good health in mothers than the
      attribute.

PMID- 15446668
TI  - [Efficacy of nurses' on the job training to better advise cessation among
      hospitalized smokers].
AB  - OBJECTIVES: The article describes the framework of an on-the-job training program
      for nurses that teaches them how to better advise hospitalized smokers to stop
      smoking. The purpose of the study was to evaluate the efficacy of the program.
      METHODS: We corducted an on-the-job training program for 4 years aimed at nurses
      who worked in 2 of 11 wards in our hospital (training wards). The aim of the
      training program that we developed was to improve nurses' self-efficacy in
      advising and supporting patients to stop smoking. An average of 40 nurses worked
      in the two wards at any time during the study period. A self-administered
      questionnaire was given to nurses working at our hospital before (in 1997) and
      after (in 2002) the program was undertaken. Changes in cognition and behavior
      with regard to advice to hospitalized smokers were also compared between nurses
      working at the training wards and nurses working in the other wards in question,
      whose number averaged 200 nurses during the period. RESULTS: There were no
      differences in age distribution, smoking habits and epidemiological knowledge of
      smoking between the two groups. Self-efficacy in advising and supporting patients
      to cease smoking was significantly increased among nurses working in the training
      wards (P=0.02), whereas no significant increase with time was found among nurses
      working in the other wards (P=0.14). After the program was undertaken, nurses
      working in the training wards had a significantly higher proportion who always
      advised hospital smokers to quit according to their predictable stage of change
      than their counter parts working in the other wards (adjusted odds ratio 2.93,
      95% confidence interval 1.27-6.74). CONCLUSION: The study indicates the job
      training program to have improved the nurses' self-efficacy, appearing to change
      their behavior in advising and supporting patients to cease smoking.

PMID- 15446669
TI  - [Evaluation of demographic factors for autonomy of the elderly and their families
      in selecting long-term care insurance services].
AB  - PURPOSE: This study was conducted to characterize (1) the autonomy of service
      users, both frail elderly and of their family caregivers, in selecting Long-term
      care insurance services, and to evaluate (2) influencing demographic factors. The
      aim was to propose new directions for the care providing system. METHODS: The
      subjects were 1,760 users of public Long-term Care Insurance who were randomly
      stratified and sampled in Higashi-osaka city, Osaka prefecture. Data were
      collected through a mailed anonymous self-report questionnaire in October, 2001.
      The number returned was 1,178 (66.9%). In this study, 723 eligible cases were
      analyzed in separate models: 146 cases for the elderly model, and 577 for the
      family model. Multiple regression analysis and two-way analysis of variance were
      performed to identify factors which have direct and interactive effects,
      respectively, on the autonomy. RESULTS: 1) The degree of autonomy of the elderly
      (3.1 +/- 0.8 (range 1-4)) was high in comparison with the family (2.8 +/- 0.8).
      2) In the elderly model, the ability to collect service information and the level
      of knowledge about the service contents had a direct effect on the autonomy. In
      the family model, ability to collect service information and the level of
      knowledge about the service contents, the degree of informing the provider of own
      care needs, and good relations among family members had direct effects. 3) In the
      elderly model significant two-way interactive effects on the autonomy were
      observed between the level of knowledge about the service contents and the age;
      attitudes of the service providers and the age or gender of the recipient; the
      degree of informing the provider of own care needs and the gender. In the family
      model, significant interactions were noted between the attitudes of the service
      providers and the age of the family caregiver; the level of congitive disorders
      of the elderly and the length of service usage. CONCLUSIONS: It was clarified
      that the score for autonomy of the family was low in comparison with that for
      elderly, and the essential requisites of service providers for enhancing the
      autonomy of elderly people and families may vary depending on the basic
      characteristics or the situation of the user. It was suggested that support to
      enhance users autonomy should be provided by taking the demographic factors of
      the user into consideration.

PMID- 15446670
TI  - [What kind of family makes a case difficult? Public health nurses' views on home
      care for the frail elderly].
AB  - OBJECTIVE: Public health nurses (PHNs) played the major role in providing care
      management for the frail elderly before the Long-term Care Insurance started in
      2000. Although the role of care management has now shifted to care managers, PHNs
      are still consulted by such care managers, service providers and families of the
      elderly about long-term home care. The purpose of this study was to explore the
      factors that make a case difficult to deal with from PHNs' viewpoint. This study
      focuses on the factors related to family living in the same household (living
      together family). SUBJECTS AND METHODS: The informants of this study were seven
      PHNs who worked for a city with a population of 67,000 (proportion of elderly in
      the whole population is 19%) in Nagano Prefecture. First, a focus group interview
      (about 90 minutes) with the six PHNs was conducted to extract an outline of
      difficult cases. Next, semi-structured interviews (about 60 minutes each) with
      five PHNs were conducted to obtain detailed information on difficult cases. The
      interviews were tape-recorded and transcribed verbatim. KJ analysis was conducted
      by defining characteristics, finding similar factors, and grouping these together
      to form categories. RESULTS: Categories of family related problems emerged for
      each of two major categories: family characteristics and care related problems.
      Firstly, existing family characteristics, including the existence of mental or
      psychological disorders, low motivation towards providing long-term care,
      conflictual familial relationships, objections to having service providers in the
      home, and economic difficulties contribute to problems in providing long-term
      care with living-together families. These characteristics can lead to a second
      set of problems, relating to the actual provision of care by the living-together
      family to frail elderly patients. These care related problems include including
      insufficient care, rejection of formal care services, and deviation from care
      directives, including to the point of physical mistreatment. CONCLUSION: This
      study points to the need for care providers to consider the living-together
      family's background and the potential for the phenomena, indicated in this study,
      to negatively impact on the provision of care for the frail elderly.

PMID- 15446671
TI  - [A survey regarding the implementation of cancer screening among municipalities
      in Japan].
AB  - OBJECTIVE: The objective of this study was to conduct a survey regarding
      implementation of cancer screening in all municipalities in Japan. METHODS: In
      February 2003, we sent out a questionnaire regarding cancer screening to all
      3,242 municipalities in Japan. RESULTS: A total of 2,342 municipalities (72.2%)
      completed and returned the questionnaire. In the year 2002, the percentages of
      municipalities which implemented each cancer screening were 49.4% for breast
      cancer using mammography, 33.7% for prostate cancer, 20.3% for cervical cancer
      for women younger than 30 years old, 5.7% for lung cancer using helical CT, 5.0%
      for gastric cancer using the PG method and 4.8% for ovarian cancer. CONCLUSIONS:
      Screening for breast cancer using mammography, as recommended by the 4-th plan
      for Health Services for the Aged, was implemented by less than half of the
      municipalities. Parameters, including eligible age group, target group, and
      method, widely differed among the municipalities. A standardized system for
      cancer screening programs should be recommended.

PMID- 15446672
TI  - [A survey on smoking behavior in Hokkaido University School of Medicine, 2003].
AB  - OBJECTIVE: A survey was carried out to assess smoking among students, and
      administration and teaching staff in Hokkaido University School of Medicine in
      2003. METHODS: We conducted a questionnaire survey on smoking of undergraduates,
      graduate students, administration personnel and teaching staff in Hokkaido
      University School of Medicine in February 2003. The majority of question items
      were targeted for all subjects while some items were addressed separately to
      smokers, ex-smokers and non-smokers. RESULTS AND DISCUSSION: The survey showed
      that 1) the smoking rate of the study subjects is lower than that of physicians,
      in general; 2) dependence on cigarettes among smokers is relatively low; and 3)
      80% of the ex-smokers are in the maintenance stage, while 20% are in the action
      stage. Furthermore, 1) there was a tendency for smokers and non-smokers to be
      concerned with the health effects of passive smoking than that of active smoking;
      2) smokers tended to ignore the unpleasant smell of cigarettes as compared with
      ex-smokers and non-smokers; 3) although the three groups acknowledged the health
      affects of smoking, they are not proactive in the promotion of anti-smoking; and
      4) everyone is generally concerned with the smell of cigarettes but tended to
      accept it in the school of medicine. CONCLUSIONS: It is an important issue how
      smokers in the interested stage can move to the anti-smoking stage, and how those
      in the action stage shift to the maintenance stage. We have carried out anti
      smoking events and campaigns on the campus based on the results of the survey and
      further plan to formulate a strategy for anti-smoking on the campus. The specific
      activities will be undertaken and the results evaluated in future.

PMID- 15446673
TI  - [Weight-control intervention in overweight subjects at high risk of
      cardiovascular disease: a trial of a public health practical training program in
      a medical school].
AB  - OBJECTIVE: To evaluate the effectiveness of a weight-control intervention for
      overweight subjects at high risk of cardiovascular disease (CVD) at a worksite
      conducted by medical students as a public health practical training program.
      METHODS: A total of 45 men and women who were obese (BMI > or = 24.0 kg/m2) and
      found to be hypertensive (SBP > or = 140 mmHg or DBP > or = 90 mmHg) or suffering
      from hypercholesterolemia (total serum cholesterol > or = 220 mg/dl) in an annual
      health check up in November 2001 were invited to participate in a weight-control
      intervention program. Eight individuals agreed (intervention group) and other
      sixteen control subjects whose sex and age (+/- 3 years) were matched to the
      intervention subjects were selected. The duration of the program was three months
      (from July to October 2002) and a 2 kg weight reduction in that period was set as
      the goal. The baseline survey consisted of a dietary questionnaire and a health
      quiz. Subjects had two counseling sessions and received four personal letters in
      the three months. A semi-quantitative food frequent questionnaire, a photograph
      method (Diet Agent Service, Matsushita Electric Works, Ltd.) and three day food
      records were conducted for dietary surveys. Changes in bodyweight, BMI, blood
      pressure, and serum total cholesterol concentration from November 2001 to
      November 2002 were compared between the intervention and control groups. Food
      group intakes and nutrient intakes were compared between weight reduction
      achievers and non-achievers. RESULTS: Mean bodyweight changes from November 2001
      to November 2002 were -2.3 kg (SD 3.3 kg) for the intervention group and +0.3 kg
      (SD 1.5 kg) for the control group, the difference being significant (p = 0.013).
      For the intervention group mean bodyweight change from July to October 2002 was 
      1.5 kg (SD 2.4 kg). For total serum cholesterol, the mean changes were -32.1
      mg/dl vs. +0.5 mg/dl (p = 0.005), for SBP -9.5 mmHg vs. +4.7 mmHg (p = 0.083) and
      for DBP -2.8 mmHg vs. +1.4 mmHg (p = 0.438). These were thought to be
      consequences of weight-control intervention. From dietary surveys, weight
      reduction achievers increased fish intake and decreased fats, snacks and sweets.
      Those who answered the health quiz more correctly demonstrated more reduction of
      bodyweight. CONCLUSIONS: Effectiveness of a weight-control intervention for
      reduction of CVD risk factors was found in the present public health practical
      training program for medical students. Dietary advice based on various dietary
      surveys was indicated to be effective in the weight-control program. A population
      strategy to distribute health information appeared necessary for effective health
      education programs for high-risk subjects.

PMID- 15446674
TI  - [The influences of nitrous oxide and ketamine on electroencephalogram during
      propofol-anesthesia].
AB  - BACKGROUND: The influence of nitrous oxide and ketamine on electroencephalogram
      (EEG) during the induction of general anesthesia with propofol was quantitatively
      analyzed. METHODS: Anesthesia was induced with propofol using TCI (target
      controlled infusion) system. Twenty-five adult patients (ASA I-II) were randomly
      divided into three groups: 1. anesthesia induced with propofol alone [Group-P
      (n=7)], 2. anesthesia induced with inhalation of nitrous oxide in addition to
      propofol [Group-PN (n= 10)] and 3. anesthesia induced with intravenous injection
      of ketamine in addition to propofol [Group-PK (n= 8)]. We studied the influence
      of nitrous oxide and ketamine on EEG by analyzing the relations between effect
      site concentration of propofol and EEG-indices. RESULTS: Additional injection of
      ketamine (Group-PK) increased BIS index during the maintenance of anesthesia from
      43.4 +/- 8.2 to 71.8 +/- 6.5 in comparison with the contrasting group (Group-P).
      Nitrous oxide also increased the high frequency component in EEG. CONCLUSIONS:
      When anesthesia is induced with nitrous oxide and/or ketamine together with
      propofol, and BIS is taken as an index of depth of anesthesia, the intracerebral
      concentration of propofol becomes excess.

PMID- 15446675
TI  - [Volatile anesthetics and synaptic transmission in the central nervous system].
AB  - Long-lasting changes in the synaptic efficacy of signaling between neurons in the
      central nervous system are thought to be involved in memory consolidation and
      recall. Such long-lasting changes were first demonstrated by Bliss et al. in
      1973. They found that high frequency stimulation to the hippocampus produced an
      increase in the amplitude of excitatory postsynaptic potentials, which lasted at
      least for hours. This phenomenon is known as long-term potentiation (LTP). LTP
      occurs in many synaptic pathways, and some forms of LTP appear to be triggered by
      the influx of calcium through NMDA receptors. General anesthetics are thought to
      affect LTP, since clinically relevant concentrations of volatile anesthetics seem
      to modify ligand-gated ion channels such as glutamate receptors and GABA(A)
      receptors. Previous studies have shown that volatile anesthetics such as
      isoflurane and sevoflurane enhance GABA(A) receptor-mediated inhibition,
      suggesting that general anesthesia is produced, at least in part, by enhancing
      neural inhibition mediated by GABA(A) receptors. This review focuses on recent
      research concerning the effects of volatile anesthetics on synaptic transmission,
      synaptic plasticity, and clinically important diseases imparing synaptic
      transmission in the central nervous system.

PMID- 15446676
TI  - [Criteria for postoperative discharge of the patients managed by
      anesthesiologists in an ambulatory surgery unit].
AB  - BACKGROUND: Postoperative care following ambulatory surgery is done at home.
      Therefore, it is important to establish qualitative clinical discharge criteria
      that can be used to determine when patients can go home safely for the care by
      friend or relative. METHODS: This study included 213 patients who had been
      managed by anesthesiologist in an ambulatory surgery unit. We compared the
      discharge times achieved by post-anesthesia discharge scoring system with the
      times that the patients were actually discharged from the ambulatory surgery
      unit. RESULTS: On an average, patients who could be discharged safely on the same
      day required 161 minutes postoperatively to achieve a post-anesthesia discharge
      score of at least 9. The actual postoperative discharge time was 255 minutes.
      53.6% of the patients who had been admitted could have obtained a post-anesthesia
      discharge score of at least 9, but they wanted to stay in hospital. CONCLUSIONS:
      A discharge scoring system is effective to determine the optimal length of stay
      in the ambulatory surgery unit and to achieve the prompt and safe discharge of
      patients. In order to popularize ambulatory surgery and reduce admission rate, it
      is necessary for us to make an effort to change patients' mind for ambulatory
      surgery.

PMID- 15446677
TI  - [Relationship between driving pressure and tidal volume during high frequency jet
      ventilation for the tracheal resection].
AB  - BACKGROUND: High frequency jet ventilation (HFJV) is a method of ventilation for
      tracheal resection because it provides a good surgical field and decreases
      surgical complications. We should know ventilatory settings of HFJV to perform
      safe respiratory management. In this study we evaluated the relationship between
      tidal volume (VT) and driving pressure (DP) during HFJV for tracheal resection.
      METHODS: Twenty patients undergoing tracheal resection under total intravenous
      anesthesia were studied. Jet pulse was delivered through a 12 or 15 Fr feeding
      catheter connected to a jet ventilator. We set DP optionally and inspired oxygen
      concentration 100%, ventilatory frequency 100 x min(-1), and I/T ratio 0.3 or
      0.5. In fourteen patients receiving HFJV with 15 Fr catheter we calculated VT by
      measured PaCO2, reported VCO2 value, and physiological dead space (1.1 x body
      weight) for each patient and evaluated relationship between VT and DP. RESULTS:
      HFJV was feasible in all patients. Pneumothrax occurred in one patient.
      Respiratory complications including pneumonia and respiratory failure were not
      observed after surgery in all patients. The calculated VT values showed a
      significant correlation with DP (VT = 48.1 DP + 44.7, r=0.73, P<0.01).
      CONCLUSIONS: In respiratory management for tracheal resection with HFJV, we can
      predict DP from VT calculated by expected PaCO2, reported VCO2 value, and
      physiological dead space. It enables us to perform safe respiratory management.

PMID- 15446678
TI  - [Combined spinal and epidural anesthesia for cesarean section: a retrospective
      study with 0.5% hyperbaric bupivacaine].
AB  - BACKGROUND: We investigated retrospectively the relationship between the
      intrathecal dose of 0.5% hyperbaric bupivacaine and the use of 2% mepivacaine
      through an epidural catheter. METHODS: Forty-nine patients undergoing cesarean
      section with combined spinal and epidural anesthesia (CSEA) were analyzed. They
      were divided into two groups; with (CSEA group) and without additional epidural
      injection group (spinal group). RESULTS: In the CSEA group (24 patients received
      1.2 +/- 0.4 ml of 0.5% hyperbaric bupivacaine), 5-10 ml of 2% mepivacaine were
      required to achieve the adequate surgical anesthesia. In the spinal group (25
      patients received 1.6 +/- 0.3 ml of 0.5% hyperbaric bupivacaine), cesarean
      section was performed without additional mepivacaine before delivery. The
      analgesic level and the amount of fluid infusion were similar in the two groups.
      However, 20% of patients in the spinal group showed hypotension (systolic blood
      pressure below 80 mmHg), although no patients in the CSEA group developed
      hypotension. The amount of ephedrine used before delivery was significantly
      larger in the spinal group (8.9 +/- 7.7 mg) than in the CSEA group (3.9 +/- 4.3
      mg). CONCLUSIONS: Spinal anesthesia induced by 1.2 ml of 0.5% hyperbaric
      bupivacaine with sequential epidural block induced by 5-10 ml of 2% mepivacaine
      caused no hypotension during cesarean section.

PMID- 15446679
TI  - [Fast-track cardiac anesthesia and perioperative management appropriate for early
      rehabilitation after coronary artery bypass graft (CABG) surgery].
AB  - BACKGROUND: Rapid mobilization and rehabilitation after CABG has a potential
      benefit of reducing both costs and pulmonary complications (such as atelectasis
      and pulmonary embolism). Moreover, it improves the patient's emotional recovery.
      We performed fast-track cardiac anesthesia aiming toward early rehabilitation.
      METHODS: Patients undergoing CABG surgery (total, 140: on-pump 97, off-pump 43)
      were studied. Anesthesia was induced and maintained with low doses of fentanyl
      and propofol. The outcome of our perioperative management was retrospectively
      reviewed on the basis of clinical records. RESULTS: The duration of the operation
      was 282 +/- 71 min. Anesthesia time was 353 +/- 72 min. The doses of fentanyl and
      propofol were 11.9 +/- 2.9 microg x kg(-1) and 16.8 +/- 5.4 mg x kg(-1),
      respectively. Time to extubation was 213 +/- 676 min, and the percentage of cases
      extubated within 3 h was 82%. As for outcome, the percentages of first oral
      intake, first rising from bed, and first gait performed on postoperative day 1
      were 92%, 78%, 61%, respectively. The period of ICU stay was 2 days (median
      value). There were no perioperative complications related to early
      rehabilitation. CONCLUSIONS: We can safely manage fast-track cardiac anesthesia
      and perioperative management aiming toward early rehabilitation after CABG
      surgery.

PMID- 15446680
TI  - [Two cases of gravity dependent atelectasis after laparoscopic nephrectomy].
AB  - Two patients developed postoperative pulmonary atelectasis after receving
      laparoscopic nephrectomy in the lateral kidney position. In both patients, the
      trachea was intubated with a single lumen tube and the lateral kidney position
      was kept over 9 hours. Because the pulmonary atelectasis had developed on the
      lower side of the lungs, we considered it as the gravity dependent atelectasis
      (GDA). We have also described treatments and prophylaxis for GDA in this case
      report.

PMID- 15446681
TI  - [Postoperative laryngeal edema presumably due to hypoalbuminemia causing acute
      airway obstruction after extubation in a patient after nephrectomy].
AB  - We report here a case of upper airway obstruction occurring after extubation in a
      55-yr-old 60 kg man after elective nephrectomy. Anesthesia was maintained with O2
      (33%), N2O, sevoflurane (1.5-2%), and propofol infusion (2 mg x kg(-1) x hr(-1)).
      Blood loss was 1,965 ml, part of which was substituted by blood transfusion and
      albumin infusion. After surgery, the patient recovered uneventfully and could be
      extubated shortly. Twenty minutes after extubation, he developed dyspnea
      progressively with stridor and became cyanotic despite the use of oxygen mask and
      assisted ventilation. Oxygen saturation decreased gradually, and bradycardia (<30
      beats x min(-1)) and severe hypotension were also observed. Cardiopulmonary
      resuscitation using epinephrine was immediately started. Re-intubation of the
      trachea was difficult due to severe edema, but eventually performed using a tube
      of a smaller size (internal diameter 7.0 mm). Subsequent investigations using a
      fiberscope confirmed extensive soft tissue swelling, maximal at the level of the
      vocal cord and extending up- and down-wards to the trachea, indicating that the
      obstruction is caused by severe laryngeal edema. We believe that edema may have
      been caused by hypoalbuminemia (1.3 g x dl(-1)) at the end of operation.
      Therefore, it should be noted that hypoalbuminemia may cause laryngeal edema
      leading to acute airway obstruction.

PMID- 15446682
TI  - [Ventricular tachycardia induced by the change of position for epidural catheter
      insertion in a patient with hypertrophic obstructive cardiomyopathy].
AB  - We report here a case of ventricular tachycardia (VT) induced by the change of
      position for insertion of an epidural catheter before the induction of general
      anesthesia. A 79-yr-old woman was scheduled for elective right lung surgery. Past
      history included hypertension and hypertrophic obstructive cardiomyopathy (HOCM),
      which were treated with a calcium channel blocker and an anti-arrhythmic drug.
      Preoperative echocardiogram (ECG) showed first degree arterio-ventricular block
      and left ventricular hypertrophy. Before the induction of general anesthesia, the
      patient was turned into the left lateral position for the insertion of an
      epidural catheter. Shortly after the change of position, ECG showed transient VT,
      which lasted for approximately 40 sec, and she was forced to be turned to the
      supine position and required recovery for a time. VT was successfully treated and
      terminated by changing to the supine position and intravenous injection of 2%
      lidocaine (2 ml). The left radial artery was cannulated for monitoring arterial
      blood pressure and sampling. Since no abnormality was observed in ECG for the
      next twenty minutes, the patient was turned to the left lateral position again
      and epidural catheterization was performed through T 7-8 interspace. Considering
      some risk factors such as intraoperative change of position, the surgery was
      cancelled on that day. Postoperatively amiodarone was used and an implantable
      cardioverter defibrillator (ICD) was planted for risk reduction of sudden cardiac
      death due to ventricular arrhythmia. The cause of VT in our case is not certain;
      we believe that VT might be closely related to the left lateral position,
      especially keeping of the forward-bending position, which might cause compression
      to the heart and produce stenosis of the left ventricular outflow tract. It
      should be noted that severe tachyarrhythmia might occur after turning patients
      with HOCM.

PMID- 15446683
TI  - [A patient with a huge posterior mediastinal tumor and ST-segment depression in
      electrocardiogram].
AB  - A 68-year-old woman had felt a chest and back pain for 3 months. Gradually her
      symptom became aggravated, and she felt severe dyspnea in supine position and
      dysphagia combined with superior vena cava syndrome. A huge posterior mediastinal
      tumor was revealed and her esophagus was severely narrowed on the chest MRI.
      Therefore, emergency tumor resection was scheduled under general anesthesia.
      Anesthesia was induced by midazolam (2 mg) with the patient in the right lateral
      position. After gas exchange and oxygenation were comfirmed by pulse oximetry
      reading and clinical signs, she was slowly turned to supine position. But,
      suddenly, ST-segment depression and low amplitude developed in electrocardiogram
      and systolic blood pressure was depressed to below 60 mmHg. Therefore, she was
      rapidly retuned to right lateral position, and ST-segment and systolic blood
      pressure recoverd. On the next time, although she was slowly turned to the right
      semi-lateral position, there was almost no circulatory failure. A bronchial tube
      was intubated in her left bronchia under bronchoscope. We should remember that
      the preparation of percutaneous cardiopulmonary support (PCPS) should be
      considered as a means of protection against cardiovascular collapse or airway
      obstruction perioperatively.

PMID- 15446684
TI  - [Successful control of rapid heart rate with atrial flutter by intravenous
      administration of esmolol in a patient after total correction of the tetralogy of
      Fallot].
AB  - A 30-year-old woman with atrial flutter after surgical correction of tetralogy of
      Fallot, underwent gynecological procedure under general anesthesia. Because she
      had been noted to have atrial flutter and heart failure at 8 weeks' gestation,
      she was scheduled for dilatation and curettage. Chest X-ray film showed
      cardiomegaly and pulmonary congestive changes. ECG showed atrial flutter with 3:2
      atrio-ventricular conduction rate and complete right branch block. She was
      anesthetized with propofol infused with target-controlled infusion system,
      fentanyl and 66% of nitrous oxide under close monitoring and appropriate
      respiratory management. The quantity of hemorrhage was about 850 ml, and
      hypovolemia was treated with volume infusion and the use of vasoactive drugs.
      Soon after emergence from anesthesia, atrial flutter with 1:1 A-V conduction (>
      230 bpm) occurred suddenly. Esmolol hydrochloride, 30 mg, was administered.
      Despite the relatively low doses, rapid control of heart rate was possible in a
      few minutes and the atrial flutter returned to 2:1 conduction. Although atrial
      flutter had continued until the discharge, tachyarrhythmia was no longer observed
      and the heart resumed sinus rhythm 3 month after the operation. The present case
      suggests that esmolol can be used effectively and safely for controling atrial
      flutter with rapid ventricular response in a patient after surgical correction of
      tetralogy of Fallot.

PMID- 15446685
TI  - [Anesthetic management in a patient with Cornelia de Lange syndrome].
AB  - An eight-year-old boy with Cornelia de Lange syndrome underwent left inguinal
      hernioplasty and orchiopexy under general anesthesia. The patient with Cornelia
      de Lange syndrome had severe primordial growth failure with muscle-skeletal
      system such as cleft palate, micrognathia, and micromelia of the extremities and
      mental retardation as well as characteristic faces such as deep supercilia, etc.
      We suspected difficulty of endotracheal intubation due to this syndrome.
      Anesthesia was induced with intravenous injection of atropine 0.1 mg and ketamine
      10 mg followed by inhalation of nitrous oxide 3 l x min(-1), oxygen 3 l x min(
      1), and sevoflurane 5% without any muscle relaxant. Although his neck and
      temporomandibular joint were stiff, his trachea was intubated orally without
      difficulty with a 4.5 mm ID tracheal tube using a Macintosh laryngoscope.
      Anesthesia was maintained uneventfully by bolus intravenous injection of ketamine
      5 mg and inhalation of oxygen and sevoflurane 2-3% with mechanical ventilation.
      The anesthetic management in a patient with Cornelia de Lange syndrome should be
      carried out with careful preoperative evaluation of physical status, and
      especially the difficult endotracheal intubation should be kept in mind.
      Induction of general anesthesia with injection of ketamine followed by inhalation
      of sevoflurane without muscle relaxant is a safe method in Cornelia de Lange
      syndrome.

PMID- 15446686
TI  - [Severe acute pulmonary edema during living related liver transplantation
      surgery].
AB  - We report a case of severe intraoperative pulmonary edema during living related
      liver transplantation (LRLT) surgery. A 60-year-old woman with end-stage primary
      biliary cirrhosis underwent LRLT. After administration of several units of packed
      red blood cells and fresh frozen plasma, a gradual decline in oxygen saturation
      was observed. After an unexpectedly prolonged ahepatic phase, she developed
      severe pulmonary edema and critical hypoxemia. Further deterioration of hypoxemia
      was observed after reperfuion of the portal vein. We conclude that this severe
      pulmonary edema was caused by transfusion related acute lung injury, and
      prolonged ahepatic phase with reperfusion injury deteriorated the lung condition.

PMID- 15446687
TI  - [A comparison of two methods for continuous cardiac output measurement: PulseCO
      VS CCO].
AB  - BACKGROUND: PulseCO (PulseCO) (PulseCO Hemodynamic Monitor, LiDCO Co., London,
      England) is a low invasive apparatus to measure cardiac output continuously from
      arterial pulse waveform. CCO (774 HF 75, Edwards Lifescience Co., California,
      USA) is a continuous cardiac monitor commonly used clinically. The purpose of
      this study is to compare the accuracy of these two methods for cardiac output
      measurement with the thermodilution technique (TDCO) as control. METHODS: To
      compare the accuracy of PulseCO with that of CCO, six patients with pulmonary
      artery catheter inserted were recruited. PulseCO and CCO were measured
      continuously, and these CO values were compared with TDCO measurements every
      hour. RESULTS: Correlation with TDCO was examined in PulseCO (r=0.82) and CCO
      (r=0.80). CONCLUSIONS: PulseCO was low invasive, and showed a significantly
      better correlation with TDCO, compared with CCO.

PMID- 15446688
TI  - [Anesthetic management of patients with hypertrophic obstructive cardiomyopathy
      undergoing non-cardiac surgery].
AB  - BACKGROUND: A considerable amount of data are available regarding cardiac risk in
      patients with coronary artery disease undergoing non-cardiac surgery, but few
      data are available regarding risk for patients with cardiomyopathy. METHODS:
      Reports on the anesthetic management of patients with hypertrophic obstructive
      cardiomyopathy (HOCM) undergoing non-cardiac surgery were identified using
      Medline and the Igaku-Chuou-Zassi (Japana Centra Revuo Medicina) database (1981
      2002). The data were analyzed in terms of patient characteristics, methods of
      intraoperative care, and clinical outcome. RESULTS: Sixty nine patients were
      included. The mean value of the left ventricular outflow tract pressure gradient
      (LVOTPG) was 63 mmHg. Twenty two cases were diagnosed as severe HOCM in terms of
      pressure gradient (LVOTPG > or = 50 mmHg) and clinical manifestations. Major
      complications, such as cardiac arrest and refractory shock, occurred in 10 cases.
      However, these perioperative risks were not correlated with severity of HOCM.
      CONCLUSIONS: Careful planning is inevitable in anesthesia for patients with HOCM.
      Although the rate of major perioperative complications is relatively low, they
      can occur unexpectedly and resemble the natural course of HOCM. In order to
      clearly elucidate risk factors for adverse perioperative outcomes, further
      analysis will be necessary as more cases are documented.

PMID- 15446689
TI  - [The workshop of cardiopulmonary resuscitation for medical doctors in Jichi
      Medical Hospital].
AB  - The Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular
      Care (ECC) established in 2000 (Guidelines 2000) are the standard for
      cardiopulmonary resuscitation (CPR) all over the world. Written guidelines based
      on Basic Life Support (BLS) and Advanced Cardiac Life Support (ACLS) are widely
      available throughout Japan and are studied by physicians but ACLS training
      courses have been made available only recently. In 2003, our hospital formed a
      committee to address standards of patient safety and one of the recommendations
      of the committee was the attendance of standardized BLS by health care workers
      and of ACLS by physicians. In May, 2003 a total of 447 physicians from our
      hospital participated in a workshop on BLS which provided lectures,
      demonstrations and a written examination. After completion of this workshop, it
      has been concluded that standardization in the area of resuscitation is
      mandatory, and efforts to disseminate this workshop to health care practitioners
      are to be undertaken.

PMID- 15446690
TI  - [Chorioamnionitis--risk factor of cerebral palsy in fullterm infants].

PMID- 15446691
TI  - [Connection between caffeine, adenosine receptors and dopamine. Coffee reduces
      the risk of Parkinson disease].

PMID- 15446692
TI  - [Treatment of severe hearing loss. Hopeful results with cochlear implants and
      nerve cell implantations].
AB  - Progress in techniques and strategies for tissue engineering has increased our
      interest in allografting and xenografting in various organ systems. Previous work
      has shown that peripherally implanted fetal dorsal root ganglion neurons (DRGs)
      can grow axons across the boundary between the central and peripheral nervous
      system in the dorsal root and make functional connections within the spinal cord.
      We have extended this experimental paradigm to the auditory system and
      successfully implanted fetal DRG neurons into the normal and deafened cochlea,
      adjacent to deafferented auditory spiral ganglion neurons. These findings
      demonstrate the feasibility of using fetal sensory cells in a new strategy to
      repair or replace the auditory nerve. Further studies will show whether the
      surviving DRGs can restore a functional conduit from the cochlea to the
      brainstem. If so, implanting neuronal tissue close to the auditory nerve could be
      used to regain auditory function in e.g. profoundly deaf patients.

PMID- 15446693
TI  - [Complications during the neonatal period can cause visual impairment later in
      life. Only few of the children were born prematurely--a surprising result of the
      study].
AB  - Forty per cent of children known at our low vision centre at the Department of
      Ophthalmology, University Hospital, Linkoping, Sweden, had been treated in a
      neonatal ward after birth. Only few of them were born prematurely. Half of the
      children had an additional neurological handicap. The present neonatal screening
      program detects most cases of congenital cataract and all cases with retinopathy
      of prematurity.

PMID- 15446694
TI  - [Pseudovasculitis--confusingly alike systemic vasculitis...but completely
      different treatment is required].
AB  - "Vasculitis mimicry" or "pseudovasculitis" are terms used for the description of
      a variety of disorders that simulate systemic vasculitis and often represent a
      challenge in daily rheumatological practice. These conditions may present with
      clinical, radiological, and laboratory features resembling those of systemic
      vasculitis. Nevertheless, the pathogenesis, therapeutic approach, and prognosis
      are different. The pseudovasculitides constitute an extremely heterogenous group
      of disorders with conditions caused by infections, malignancies, drugs and
      thromboembolism. A detailed history is mandatory and this should include dietary
      habits, concurrent medication, recent infections or invasive investigative
      procedures such as PTCA or conventional angiography. Incorrect diagnosis may lead
      to serious consequences due to delay of appropriate management and exposure of
      the patients to the risks of potentially toxic drugs. Thus, pseudovasculitis must
      be part of the differential diagnosis of patients presenting with manifestations
      of systemic vasculitis.

PMID- 15446695
TI  - [The effect of polyethylene glycol in chronic constipation is not sufficiently
      evaluated. A systematic literature review].
AB  - Five studies compared polyethylene glycol (PEG), an osmotic laxative, with
      placebo. In two studies the comparison was lactulose and in one study two
      different doses of PEG 3350 and PEG 4000, respectively were evaluated. PEG is
      associated with an increase in bowel movement frequency when compared with
      placebo. There was inadequate evidence to establish whether PEG was superior to
      lactulose. Data from elderly patients are lacking and data from patients with
      constipation due to Parkinson's disease, multiple sclerosis or opioid therapy was
      only evaluated in two very small studies. Severe side-effects with PEG are rare.
      There are no convincing data regarding the superiority with PEG in flatulence. On
      the whole there is a real lack of research into treatment of the chronic
      constipation in adults as well as in the elderly.

PMID- 15446696
TI  - [It's possible to influence prescriptions patterns by producer-independent
      information].
AB  - Following the publication of a metaanalysis over effectiveness and tolerability
      of triptanes for acute treatment of migraine we investigated whether a short oral
      information by clinical pharmacologists, describing the rationale for prescribing
      a certain triptane, combined with memory cards could influence the prescription
      by general practitioners. The primary care units, which had received the
      information, showed a significantly better adherence to prescription of the
      recommended triptane than units that had not received such information. The
      desired influence on prescription was, however, transient and not statistically
      significant for more than three months following the prescription. The finding
      underlines the need for repeated information when effects on prescription habits
      are wanted.

PMID- 15446697
TI  - [Registries contribute to better breast cancer care].

PMID- 15446698
TI  - [Has it become more difficult to be a physician?].

PMID- 15446699
TI  - [Thyrotoxic crisis--the last disease of Mozart?].

PMID- 15446700
TI  - [How did we handle suspected cases of SARS? Did alarming media reports frighten
      health personnel?].

PMID- 15446701
TI  - [Is continuation of CPR longer than five minutes meaningful?].

PMID- 15446703
TI  - [Individual physicians should not be broken by errors in administrative
      routines!].

PMID- 15446704
TI  - [Advantages with pencil point needle versus Quincke].

PMID- 15446705
TI  - Carbon use, nitrogen use, and isotopic fractionation of ectomycorrhizal and
      saprotrophic fungi in natural abundance and 13C-labelled cultures.
AB  - Stable isotopes in fruit bodies from field studies have been used to infer
      ectomycorrhizal or saprotrophic status and to understand carbon and nitrogen use,
      but few controlled culture studies have correlated source and fungal isotopic
      patterns. Here, we measured natural abundances of 15N and 13C in ten strains of
      ectomycorrhizal fungi and seven strains of saprotrophic fungi grown on agar with
      three different primary carbon sources: glucose, glucose plus malt extract, and
      potato dextrose agar. Eight fungal strains were also grown using position
      specific, 13C-labelled glucose (C-1 through C-6 labelled). Most fungi resembled
      nitrogen sources in delta 15N, suggesting that growth on agar media minimizes
      isotopic fractionation on uptake compared to growth on liquid media, and that in
      general saprotrophic and mycorrhizal fungi process nitrogen similarly.
      Saprotrophic fungi were more depleted in 13C than ectomycorrhizal fungi on all
      media, presumably because of assimilation of 13C-depleted, agar-derived carbon.
      Results on 13C-enriched glucose indicated that saprotrophic fungi obtained up to
      45 % of their carbon from the agar substrate. Fungi generally incorporated the
      individual carbon atoms of glucose in the order, C-4 < C-1 < C-2, C-3, C-5 < C-6,
      ranging from a mean of 9 % for the C-4 atom to 21 % for the C-6 atom. Based on
      these incorporation patterns and intramolecular 13C patterns within glucose,
      differential incorporation of carbon atoms within glucose among fungal taxa
      contributed less than 1% to isotopic differences among taxa, whereas isotopic
      fractionation among taxa during metabolism varied up to 4%. Parallel studies of
      13C-enriched and natural abundance substrates were crucial to interpreting our
      results.

PMID- 15446706
TI  - The phylogenetic position of Spathulospora based on DNA sequences from dried
      herbarium material.
AB  - The phylogenetic position of the marine ascomycete genus Spathulospora was
      investigated using partial SSU and LSU DNA sequences obtained from dried
      herbarium specimens. Spathulospora was represented by the two species S. adelpha
      and S. antarctica. Phylogenetic analyses using Bayesian, parsimony, and neighbour
      joining algorithms on SSU and LSU data sets agreed with the placement of
      Spathulospora. Both Spathulospora species are each others closest relatives, and
      group within the Lulworthiales (Sordariomycetes, Ascomycota) with support in all
      analyses. Members of the morphologically similar insect parasites in the
      Laboulbeniomycetes are not closely related to Spathulospora. Despite several
      striking morphological differences between Spathulospora and Lulworthiales, an
      important shared morphological character was found that until now had not been
      recognized. Ascospores of Spathulospora and some members of the Lulworthiales
      have apical chambers containing mucus believed to be involved in ascospore
      attachment. A closest relative to Spathulospora could not be determined.

PMID- 15446707
TI  - Molecular studies on terricolous microfungi reveal novel anamorphs of two Tuber
      species.
AB  - This study reports novel terricolous mitosporic fungal morphs nested in the genus
      Tuber according to molecular phylogenetic analysis. Fungal DNA was amplified
      directly from field-collected anamorph samples. Nuclear ribosomal DNA (nrDNA)
      sequences including the ITS regions and the D1 and D2 domains of the LSU identify
      the anamorphs as mitosporic Tuber borchii and Tuber oligospermum. The link of the
      novel anamorphs to the genus Tuber is confirmed by the comparative analysis of
      five collections from four sampling sites. Ectomycorrhizas with characteristic
      features of Tuber borchii ectomycorrhizas were found in the soil volume collected
      with one of the mitosporic T. borchii collections. A nrDNA sequence amplified
      from these ectomycorrhizae is identical with the corresponding anamorph sequence.
      The possible role of the newly discovered anamorphs in the Tuber life-cycle and
      the potential significance of anamorphs for the propagation of ectomycorrhizal
      fungi are discussed.

PMID- 15446708
TI  - Phylogenetic analysis of the bluestain fungus Ophiostoma minus based on partial
      ITS rDNA and beta-tubulin gene sequences.
AB  - In an attempt to clarify the relationship between fungi classified as Ophiostoma
      minus, but of different geographic origins and mating systems, sequencing of the
      5.8S and ITS 2 rDNA, and beta-tubulin gene was carried out. The beta-tubulin gene
      was highly informative, supporting the sub-division of O. minus into two groups
      based on geographic origin. Furthermore, isolates previously classified as O.
      pseudotsugae were confirmed as being clearly distinct from O. minus. However,
      sequencing did not reveal any polymorphisms between isolates with homothallic as
      compared to heterothallic mating systems. This was supported by crosses using
      methylbenzamidazole-2-yl carbamate nuclear markers which showed that
      hybridisation between isolates of different mating systems was possible. However,
      we propose that different mating systems may still signal a divergence of
      isolates of O. minus.

PMID- 15446709
TI  - North American populations of Entoleuca mammata are genetically more variable
      than populations in Europe.
AB  - Entoleuca mammata (syn. Hypoxylon mammatum) is a damaging pathogen of Populus
      tremuloides and P. grandidentata in North America and P. tremula in Europe, where
      the fungus occurs only sporadically in alpine regions and Scandinavia. It has
      been hypothesized that E. mammata was introduced to Europe from North America. In
      this study, E. mammata isolates collected from Europe and North America were
      compared by a sequence analysis of two DNA markers derived from DNA fingerprints.
      The objective of the study was to elucidate the relationship between North
      American and European E. mammata populations by testing two hypotheses: (1) North
      American and European isolates are conspecific; and (2) the fungus was introduced
      between continents causing both a founder effect and a genetic bottleneck. North
      American populations were found to be more polymorphic, but no major phylogenetic
      differences between fungal isolates collected from different continents were
      found. This result combined with the historical observations of the disease in
      Europe implies that E. mammata was introduced to Europe several centuries ago.

PMID- 15446710
TI  - Plectosporium alismatis comb. nov. a new placement for the Alismataceae pathogen
      Rhynchosporium alismatis.
AB  - The phytopathogen Rhynchosporium alismatis, occurring on Alisma, Sagittaria and
      other genera in the Alismataceae, is under investigation as a mycoherbicide for
      alismataceous weeds in Australian rice crops. The type species of Rhynchosporium,
      R. secalis, belongs in the Helotiales while the phylogenetic relationships of R.
      alismatis were unknown. To identify fungi related to R. alismatis, the internal
      transcribed spacer (ITS) region of the ribosomal DNA (ITS1, 5.8S rRNA gene, ITS2)
      of 56 isolates was sequenced and compared to those available in databases.
      Analysis of ITS sequences revealed close relationships between R. alismatis and
      the teleomorph genus Plectosphaerella, as well as several anamorphic fungi which
      were primarily species of Verticillium. Rhynchosporium alismatis and
      Plectosphaerella cucumerina clustered together with 98 % bootstrap support.
      Morphological comparisons supported this relationship indicating that R.
      alismatis and the anamorphic genus Plectosporium are congeneric. Rhynchosporium
      alismatis is transferred to Plectosporium, a name proposed for conservation.

PMID- 15446711
TI  - Controversy over Hygrophorus cossus settled using ITS sequence data from 200 year
      old type material.
AB  - Sowerby described Agaricus cossus in 1799. The fungus possessed a smell,
      resembling that of a wounded larva of Cossus cossus (Lepidoptera). The species
      belongs in Hygrophorus, and since more than one white Hygrophorus species has
      this distinctive smell the epithet cossus has been variously interpreted. The
      complete internal transcribed spacer (ITS) region of the original type collection
      made in 1794, preserved in the Royal Botanic Gardens Kew herbarium, was
      successfully sequenced. Comparison with the ITS sequences from four other white
      aromatic-acidulous smelling Hygrophorus species, including the type specimen of
      H. quercetorum, showed that H. cossus is a species associated with Quercus and an
      older name for H. quercetorum. The differences in basidiome colouration
      developing with age and host-tree association appear to be the most useful
      characters to discriminate between the four species with a Cossus cossus smell. A
      table of morphological and ecological characters is provided.

PMID- 15446712
TI  - A rapid molecular method for differentiating two special forms (lycopersici and
      radicis-lycopersici) of Fusarium oxysporum.
AB  - Two pathogenic special forms (f. sp.) of the Fusarium oxysporum species complex
      f. sp. lycopersici (Fol) and f. sp. radicis-lycopersici (Forl) are
      morphologically indistinguishable. Although they are pathogenic to the same host
      genus Lycopersicon (tomato), and infect the same tomato cultivar, they form
      distinct diseases; Fol causes wilt and Forl causes crown rot and root rot. These
      two special forms apparently exist as genetically isolated populations, based on
      vegetative compatibility and molecular variation at the DNA level. In seeking
      efficient diagnostic tools for differentiating Fol and Forl isolates, we examined
      three techniques: isozyme analysis, mitochondrial DNA (mtDNA) RFLP by HaeIII
      digestion of total genomic DNA, and an osmotic method using high performance
      liquid chromatography (HPLC) to detect fungal pigments. The isolates were
      collected from geographically widespread locations. Distinct HPLC-profile
      differences were found between an endophytic non-pathogenic isolate and the other
      pathogenic isolates. However, the direct mtDNA RFLP technique proved to be an
      efficient diagnostic tool for routine differentiation of Fol and Forl isolates.

PMID- 15446713
TI  - Pythium attrantheridium sp. nov.: taxonomy and comparison with related species.
AB  - Pythium attrantheridium sp. nov. is a new species isolated from cavity spot
      lesions of carrots as well as apple and cherry seedlings from various locations
      widely distributed in Canada and the USA. This fungus is closely related to the
      heterothallic P. intermedium, but is distinguished by: (1) unique molecular
      characteristics; (2) unique morphological characteristics; and (3) mating
      incompatibility with P. intermedium. The ITS region of the nuclear rDNA of all
      strains of P. attrantheridium studied is different from that of all other known
      Pythium spp. The oogonia attract a large number of antheridia when compatible
      mating types contact each other. The positive mating type produces zoospores
      unlike those of P. intermedium. Thus, biological, morphological and molecular
      data support the recognition of a new species.

PMID- 15446714
TI  - Identification by gas chromatography-mass spectrometry of the volatile organic
      compounds emitted from the wood-rotting fungi Serpula lacrymans and Coniophora
      puteana, and from Pinus sylvestris timber.
AB  - Volatile organic compounds (VOCs) emitted by two wood-rotting basidiomycete
      fungi, Serpula lacrymans (dry rot fungus) and Coniophora puteana (cellar fungus),
      and the timber of Pinus sylvestris (Scots pine), were identified. Several
      volatile collection techniques were employed including dichloromethane solvent
      extraction, solid-phase microextraction (SPME) and thermal desorption of VOCs
      entrained on Tenax GR. In addition, a new method of solid sample injection (SSI)
      is described which utilises a low injector temperature and an all-glass
      deactivated injector liner designed to minimise both the formation of pyrolysis
      products and analyte degradation. All the volatile compounds collected were
      analysed using electron impact capillary gas chromatography-mass spectrometry (GC
      MS) on HP-5, HP-Innowax and beta-cyclodextrin columns. SSI and Tenax thermal
      desorption were found to be the most effective extraction methods. A total of 19
      VOCs were observed from S. lacrymans grown on glass slides and pine, 15 from C.
      puteana grown on glass slides and 12 from P. sylvestris timber. S. lacrymans was
      found to emit, in low abundance, six unique VOCs, of which 2-methylbutanal was
      the greatest. The major volatile compound emitted by S. lacrymans was 1-octen-3
      ol, which was also found in lower abundance from C. puteana. Six VOCs, including
      diethylene glycol and 4-methyl methylbenzoate, were found to be unique to C.
      puteana, all in medium abundance: From P. sylvestris, the major volatiles
      identified were S-alpha-pinene and 3-carene.

PMID- 15446715
TI  - Discontinuous distribution of fumonisin biosynthetic genes in the Gibberella
      fujikuroi species complex.
AB  - Production of the carcinogenic mycotoxins fumonisins has been reported in several
      Fusarium species, most of which are members of the Gibberella fujikuroi (Gf)
      complex. In this study, we examined 15 Fusarium species in the Gf complex and 12
      other species for fumonisin production and the presence of fumonisin biosynthetic
      genes (FUM). Among the species within the Gf complex, fumonisin production was
      detected only in F. fujikuroi, F. globosum, F. proliferatum, F. nygamai, F.
      oxysporum and F. verticillioides. These five species include members of two of
      the three major clades delineated in the Gf complex. The FUM genes were detected
      in these same five species and in F. anthophilum, a member of the third clade.
      Among the species outside the Gf complex, fumonisin production and FUM genes were
      detected only in F. oxysporum. Phylogenetic analyses of nucleotide sequences from
      two FUM gene fragments inferred relationships similar but not identical to those
      inferred from previous analyses of other genes. The results indicate the FUM
      genes are discontinuously distributed in the Gf complex and that this
      distribution gives rise to the differences in the abilities of closely related
      Fusarium species to produce fumonisins.

PMID- 15446716
TI  - Production of gametangia by Phytophthora ramorum in vitro.
AB  - Until now gametangia have not been obtained between paired European A1 and
      American A2 isolates of Phytopthora ramorum in vitro. Their production in
      artificial culture relies on interspecific pairings. Using P. drechsleri and P.
      cambivora testers, 51 of 110 P. ramorum isolates from across Europe were all
      shown to be A1s; while 32 of 38 American isolates from across California and
      southwest Oregon were shown to be A2s. However, these interspecific pairings are
      complex, unusually slow and unpredictable. A range of culture media and
      conditions are described that were tested, unsuccessfully, with a view to
      enhancing the efficiency of the interspecific pairings. In further tests,
      gametangia were obtained between A1 and A2 isolates of P. ramorum when juvenile,
      pre-chlamydospore producing mycelia were mixed together on carrot agar. The
      gametangia formed in 3-10 d, sparsely to frequently, initially only within the
      boundaries of the mixed inocula but subsequently in the extended mycelial growth.
      Chlamydospores were also produced. This inoculum-mixing method, though again
      sometimes unpredictable, should enhance efficiency of testing for compatibility
      types and facilitate further studies on whether the sexual outcrossing system of
      P. ramorum is functional. Differences between sexual reproduction of P. ramorum
      and that of other heterothallic Phytophthora species are discussed.

PMID- 15446717
TI  - Ultrastructure of the infection process of potato tuber by Helminthosporium
      solani, causal agent of potato silver scurf.
AB  - Silver scurf is an important postharvest disease affecting potato tubers
      worldwide, caused by Helminthosporium solani. In the present study, key steps of
      infection of potato tubers (cv. 'Dark Red Norland') by H. solani were described
      using transmission (TEM) and scanning electron microscopy (SEM). The fungus
      entered potato tubers mainly via hyphae, although germ tubes were also able to
      directly penetrate the tubers. An extracellular sheath was observed around hyphae
      growing over the surface of tubers and the host cell wall appeared lyzed at the
      point of penetration. Observations suggested that both mechanical and enzymatic
      processes are involved in periderm penetration. Hyphae of H. solani, 9 h after
      tuber inoculation, were present intracellularly mostly in the periderm and in
      some cortical cells. Two days after inoculation, host cells were invaded and both
      infected and neighbouring host cells showed signs of necrosis (disrupted
      cytoplasm, absence of typical organelles or endomembrane systems, collapsed
      peridermal cells) that were not observed in healthy control tubers. Four days
      after inoculation, completing the infection cycle, conidiophores emerged from
      peridermal cells directly by erupting through the host cell walls.

PMID- 15446718
TI  - Infection process of Plectosporium alismatis on host and non-host species in the
      Alismataceae.
AB  - In Australia, the endemic fungus Plectosporium alismatis (syn. Rhynchosporium
      alismatis) has potential use as a mycoherbicide for several species in the
      Alismataceae, a family of aquatic and semi-aquatic marsh herbs, which are
      considered to be important weeds in rice crops. Of five species identified in
      south-eastern Australia where rice is grown, two species, Sagittaria graminea and
      Sagittaria montevidensis are resistant (non-hosts), and no records of P.
      alismatis on these species have been reported. To better understand the
      interactions that lead to resistance in these pathosystems, the infection process
      of the fungus was studied on these species and also on the host Alisma plantago
      aquatica, using light, fluorescent and scanning electron microscopy. On all three
      species both conidial germination and appressorium formation commenced within 6 h
      of inoculation with greater than 50 % of conidia elongating to form germ tube
      structures and associated appressoria 12-18 h post inoculation. Germ tube
      elongation and appressorium formation occurred randomly over the leaf surface.
      Direct host penetration was facilitated by the production of penetration hyphae
      that emerged from beneath appressoria. Penetration sites were clearly identified
      by the presence of spherical holes 0.25-0.5 microm in diam, and were frequently
      accompanied by resistance reactions in non-host species. Visible symptoms of
      disease occurred 4-6 d after inoculation of susceptible (host) species.

PMID- 15446719
TI  - Aecidium kalanchoe sp. nov., a new rust on Kalanchoe blossfeldiana
      (Crassulaceae).
AB  - A rust fungus found on cultivars of Kalanchoe blossfeldiana (Crassulaceae) is
      described as a new species, Aecidium kalanchoe sp. nov., and compared to the
      other described rusts on members of the Crassulaceae. Only one other rust is
      known to parasitize Kalanchoe spp. A DNA sequence of A. kalanchoe suggests that
      the teleomorph is related to Puccinia.

PMID- 15446720
TI  - Olfactory-triggered panic attacks among Khmer refugees: a contextual approach.
AB  - One hundred Khmer refugees attending a psychiatric clinic were surveyed to
      determine the prevalence of olfactory-triggered panic attacks as well as certain
      characteristics of the episodes, including trigger (i.e. type of odor),
      frequency, length, somatic symptoms, and the rate of associated flashbacks and
      catastrophic cognitions. Forty-five of the 100 patients had experienced an
      olfactory-triggered panic attack in the last month. Trauma associations and
      catastrophic cognitions (e.g. fears of a 'wind attack', 'weakness', and 'weak
      heart') were common during events of olfactory panic. Several case examples are
      presented. A multifactorial model of the generation of olfactory panic is
      adduced. The therapeutic implications of this model for the treatment of
      olfactory panic are discussed.

PMID- 15446721
TI  - An ethnographically derived measure of anxiety, depression and somatization: the
      Phan Vietnamese Psychiatric Scale.
AB  - This article describes the development and validation of the Phan Vietnamese
      Psychiatric Scale (PVPS). The PVPS was derived from Vietnamese idioms and
      cultural understandings of psychiatric and emotional distress identified from the
      Vietnamese literature and using ethnographic methods. The PVPS consists of a 26
      item depression subscale, a 13-item anxiety subscale and a 14-item somatization
      subscale. Estimates of internal consistency for the three subscales ranged from
      .87 to .95, with 4-day interval test-retest reliability ranging from .81 to .89.
      Confirmatory factor analysis supported the subscale structure, with the
      depression subscale comprising two components 'general mood disturbance' and
      'psychovegetative symptoms.' Multitrait-multimeasure analysis supported the
      construct validity of the scale. The PVPS demonstrated good criterion validity
      against case assignments by psychiatrists, naturalist healers, and structured
      diagnostic measures. The PVPS was rated as superior in clinical sensitivity and
      acceptability in comparison to other related measures.

PMID- 15446722
TI  - Parenting styles and mental health of Palestinian-Arab adolescents in Israel.
AB  - The relationship between three parenting styles (authoritarian, permissive, and
      authoritative) and the mental health of Arab adolescents was tested. It was
      hypothesized that parenting style toward boys would differ from that towards
      girls, psychological adjustment of girls would differ from that of boys, and that
      the authoritarian style applied within the authoritarian Arab society is not
      associated with poor psychological adjustment. The Parental Authority
      Questionnaire, Child Attitude Toward Parents, Lipsitt's Self-Concept Scale for
      Children, Rosenberg Self-Esteem Scale and the Psychological State Scale were
      administered to 431 Arab adolescents. Sex comparison revealed that the parenting
      style with regard to girls tends to be more authoritative and less authoritarian
      than with regard to boys. Girls scored higher than boys on identity disorder,
      anxiety disorder, and depression scales, whereas boys scored higher than girls on
      the behavior disorder scale. There was no significant relationship between the
      authoritarian parenting style and the mental health measures. A significant
      positive relationship exists between the authoritative parenting style and the
      mental health of children. Among boys, the permissive parenting style was
      associated with negative attitudes towards parents, lower self-esteem and
      increased identity, anxiety, phobia, depressive, and conduct disorders. It seems,
      therefore, that the effect of parenting style is culturally and gender dependent
      rather than universal.

PMID- 15446723
TI  - Depression in South Asian women living in the UK: a review of the literature with
      implications for service provision.
AB  - Research has shown that South Asian people in the UK underutilize health services
      compared with White people. Also, where services are accessed, they may not
      adequately meet cultural and religious needs. In exploring the relationship
      between the cultural and religious beliefs of South Asian service users about
      perceptions, beliefs about aetiology, cause and treatment of mental illness, past
      studies have illustrated a wide range of expectations, experiences, beliefs and
      attitudes. This article reviews research on depression in South Asian women in
      the UK, highlighting implications for services.

PMID- 15446724
TI  - Making psychiatric sense of sand: a case of delusional disorder in Saudi Arabia.
AB  - Somatic delusional disorder is an uncommon psychiatric disorder that has been
      typically reported in elderly women. This article reviews the literature and
      describes a Saudi female patient who presented with novel somatic delusion of
      turabosis--the conviction that she was continually being covered by sand from
      sandstorms. Although the systematized delusional convictions remained unshakable,
      her anxiety and mood symptoms responded to a regimen of tricyclic antidepressants
      and her delusional beliefs resolved within eight weeks of treatment with
      risperidone. Sociocultural themes and therapeutic approaches to somatic
      delusional disorder are discussed.

PMID- 15446725
TI  - Institutionalization and psychological suffering: notes on the mental health of
      institutionalized adolescents in Brazil.
AB  - This article examines the relationship between the institutionalization of needy
      children and adolescents and the resulting psychological suffering. Individuals
      who have been institutionalized for long periods suffer from increased fragility
      in psychological structure, becoming more vulnerable and at risk as a direct
      consequence of the treatment they receive in such institutions. The work
      described here is part of the Research Program on Adolescents, Mental Health and
      Culture, which is being conducted at the Child and Youth Care and Rehabilitation
      Center at the Institute of Psychiatry of the Federal University of Rio de Janeiro
      in Brazil (CARIM/IPUB/UFRJ).

PMID- 15446726
TI  - How to live to be 100.

PMID- 15446727
TI  - Eat less, live longer?

PMID- 15446728
TI  - Meet the oldest American.

PMID- 15446729
TI  - Asthma-proofing your home.

PMID- 15446730
TI  - New faces, same high standards.

PMID- 15446731
TI  - Biomolecule-functionalized carbon nanotubes: applications in nanobioelectronics.
AB  - Carbon nanotubes (CNTs) revealing metallic or semiconductive properties depending
      on the folding modes of the nanotube walls represent a novel class of nanowires.
      Different methods to separate semiconductive CNTs from conductive CNTs have been
      developed, and synthetic strategies to chemically modify the side walls or tube
      ends by molecular or biomolecular components have been reported. Tailoring hybrid
      systems consisting of CNTs and biomolecules (proteins and DNA) has rapidly
      expanded and attracted substantial research effort. The integration of
      biomaterials with CNTs enables the use of the hybrid systems as active field
      effect transistors or biosensor devices (enzyme electrodes, immunosensors, or DNA
      sensors). Also, the integration of CNTs with biomolecules has allowed the
      generation of complex nanostructures and nanocircuitry of controlled properties
      and functions. The rapid progress in this interdisciplinary field of CNT-based
      nanobioelectronics and nanobiotechnology is reviewed by summarizing the present
      scientific accomplishments, and addressing the future goals and perspectives of
      the area.

PMID- 15446732
TI  - Non-haloaluminate room-temperature ionic liquids in electrochemistry--a review.
AB  - Some twenty-five years after they first came to prominence as alternative
      electrochemical solvents, room temperature ionic liquids (RTILs) are currently
      being employed across an increasingly wide range of chemical fields. This review
      examines the current state of ionic liquid-based electrochemistry, with
      particular focus on the work of the last decade. Being composed entirely of ions
      and possesing wide electrochemical windows (often in excess of 5 volts), it is
      not difficult to see why these compounds are seen by electrochemists as
      attractive potential solvents. Accordingly, an examination of the pertinent
      properties of ionic liquids is presented, followed by an assessment of their
      application to date across the various electrochemical disciplines, concluding
      with an outlook viewing current problems and directions.

PMID- 15446733
TI  - No label required: protein binding at membrane interfaces visualized through
      colloid phase transitions.

PMID- 15446734
TI  - Electrochemical modulation of remote fluorescence imaging at an ordered opto
      electrochemical nanoaperture array.
AB  - An array of nanometer-sized apertures capable of electrochemically modulating the
      fluorescence of a model analyte is presented. The device, which combines near
      field optical methods and ultramicroelectrode properties in an array format, is
      based on an etched coherent optical fiber bundle. Indeed, the fabrication steps
      produced an ordered array where each optical nanoaperture is surrounded by a ring
      shaped gold nanoelectrode. The chronoamperometric behavior of the array shows
      stable diffusion-limited quasi-steady-state response. The model analyte,
      tris(2,2'-bipyridine) ruthenium, emits fluorescence in the Ru(II) state, but not
      in the oxidized Ru(III) state. Fluorescence is excited by visible light exiting
      from each nanoaperture since light is confined to the tip apex by the gold
      coating. A fraction of the isotropically emitted luminescence is collected by the
      same nanoaperture, transmitted by the corresponding fiber core and eventually
      detected by a charge-coupled device (CCD) camera. The array format provides a
      fluorescence image resolved at the nanometric scale which covers a large
      micrometric area. Therefore the high-density array plays a bridging role between
      these two fundamental scales. We established that the opto-electrochemical
      nanoapertures are optically independent. Fluorescence of the sample collected by
      each nanoaperture is modulated by changing the potential of the nanoring
      electrodes. Reversible electrochemical switching of remote fluorescence imaging
      is performed through the opto-electrochemical nanoaperture array itself.
      Eventually this ordered structure of nanometer light sources which are
      electrochemically manipulated provides promising photonic or electro-optical
      devices for various future applications. For example, such an array has potential
      in the development of a combined SNOM-electrochemical nanoprobe array to image a
      real sample concomitantly at the nanometer and micrometer scale.

PMID- 15446735
TI  - Ethanol decomposition: C--C cleavage selectivity on Rh(111).
AB  - Ethanol adsorption, desorption and decomposition on Rh(111) have been studied by
      X-ray photoelectron spectroscopy and tem-perature-programmed desorption
      experiments. The evolution of the C is and O is core level spectra was monitored
      as a function of ethanol exposure and surface temperature. Ethanol adsorption at
      90 K results in two nonequivalent ethanol-adsorbed species at low surface
      coverage, while a third species--related to multilayer formation--appears after
      longer exposures. Upon surface annealing, ethanol undergoes both desorption and
      dissociation, thus creating intermediate surface species which further decompose
      to hydrogen, carbon monoxide and atomic carbon. Our results clearly show that C-
      C bond cleavage is the preferential dissociation channel, while C--O bond
      scission is not observed. Calculations performed within the framework of the
      unity bond index-quadratic exponent potential model, have been used to test and
      compare different competing dissociation channels, providing an estimate of
      adsorption energies and dissociation barriers.

PMID- 15446736
TI  - Noniterative biexponential fluorescence lifetime imaging in the investigation of
      cellular metabolism by means of NAD(P)H autofluorescence.
AB  - The cofactors NADH and NADPH, hereafter NAD(P)H [NAD(P)= nicotinamide adenine
      dinucleotide (phosphate)], belong to the principal endogenous indicators of
      energetic cellular metabolism. Since the metabolic activity of cells is given by
      the ratio between the concentrations of free and protein-bound NAD(P)H, the
      development of autofluorescence techniques which accurately measure the
      modifications to this ratio is particularly significant. Hitherto the methods
      applied in the monitoring of cellular metabolism have provided either imprecise
      results, due to interference of the NAD(P)H signal by perturbing factors, or they
      have required a complicated internal calibration. We employ biexponential
      fluorescence lifetime imaging (FLIM) in order to discriminate between the free
      and protein-bound NAD(P)H without any previous calibration. Thus, we have
      obtained directly, and for the first time, a high-resolution map of cellular
      metabolism, that is, an image of the contribution of the protein-bound NAD(P)H to
      the cumulative NAD(P)H fluorescence signal. Moreover, we demonstrate that protein
      NAD(P)H complexes characterised by different fluorescence lifetimes are not
      uniformly distributed all over the cell, as assumed until now, but are
      concentrated in certain cellular regions. The different fluorescence lifetimes
      indicate either different protein-NAD(P)H complexes or different bond strengths
      between NAD(P)H and the protein in these complexes. Since an important aspect in
      biological applications is to monitor the dynamics of the relevant processes
      (such as cellular metabolism), rapid dynamical techniques, for example, rapid
      biexponential fluorescence lifetime imaging, are needed. Furthermore, it is
      necessary to reduce the evaluation effort as much as possible. Most of the
      evaluation techniques in multiexponential FLIM are time-expensive iterative
      methods. The few exceptions are connected with a loss of information, for
      example, global analysis; or a loss in accuracy, for example, the rapid
      evaluation technique (RLD). We implement for the first time in FLIM a
      noniterative, nonrestrictive method originally developed by Prony for
      approximations of multiexponential decays. The accuracy of this method is
      verified in biexponential FLIM experiments in time-domain on mixtures of two
      chromophores both in homogenous and in heterogeneous media. The resulting
      fluorescence lifetimes agree (within error margins) with the lifetimes of the
      pure substances determined in monoexponential FLIM experiments. The rapidity of
      our evaluation method as compared to iterative pixel-by-pixel methods is
      evidenced by a reduction of the evaluation time by more than one order of
      magnitude. Furthermore, the applicability of this method for the biosciences is
      demonstrated in the investigation of cellular metabolism by means of NAD(P)H
      endogenous fluorescence.

PMID- 15446737
TI  - Mechanical properties of single motor molecules studied by three-dimensional
      thermal force probing in optical tweezers.
AB  - A new method combining three-dimensional (3D) force measurements in an optical
      trap with the analysis of thermally induced (Brownian) position fluctuations of a
      trapped probe was used to investigate the mechanical properties of a single
      molecule, the molecular motor kinesin. One kinesin molecule attached to the probe
      was bound in a rigorlike state to one microtubule. The optical trap was kept weak
      to measure the thermal forces acting on the probe, which were mainly
      counterbalanced by the kinesin tether. The stiffness of kinesin during stretching
      and compression with respect to its backbone axis were measured. Our results
      indicate that a section of kinesin close to the motor domain is the dominating
      element in the flexibility of the motor structure. The experiments demonstrate
      the power of 3D thermal fluctuation analysis to characterize mechanical
      properties of individual motor proteins and indicate its usefulness to study
      single molecule in general

PMID- 15446738
TI  - Identification of biotic and abiotic particles by using a combination of optical
      tweezers and in situ Raman spectroscopy.
AB  - A highly versatile setup, which introduces an optical gradient trap into a Raman
      spectrometer, is presented. The particular configuration, which consists of two
      lasers, makes trapping independent from the Raman excitation laser and allows a
      separate adjustment of the trapping and excitation wavelengths. Thus, the
      excitation wavelength can be chosen according to the needs of the application. We
      describe the successful application of an optical gradient trap on transparent as
      well as on reflective, metal-coated microparticles. Raman spectra were recorded
      from optically trapped polystyrene beads and from single biological cells (e.g.,
      erythrocytes, yeast cells). Also, metal-coated microparticles were trapped and
      used as surface enhanced Raman spectroscopy (SERS) substrates for tests on yeast
      cells. Furthermore, the optical gradient trap was combined with a SERS fiber
      probe. Raman spectra were recorded from trapped red blood cells using the SERS
      fiber probe for excitation.

PMID- 15446739
TI  - The excited-state dynamics of phycocyanobilin in dependence on the excitation
      wavelength.
AB  - The primary light-induced processes of phycocyanobilin were studied by means of
      transient-grating spectroscopy, whereby the excitation wavelength was varied over
      the spectral region of the ground-state absorption. On the basis of the results
      obtained, both the rate of the photoreaction in phycocyanobilin and the ratio of
      the decay of different excited-state species via two decay channels depend on the
      excitation wavelength. Furthermore, the formation of the photoreaction product is
      also dependent on the pump color. These data support a recently established model
      for the primary photoprocesses in phycocyanobilin. In addition, phycocyanobilin
      protonated at the basic pyrrolenine-type nitrogen atom was included in the
      transient absorption study. The decay behavior was found to be almost unchanged
      when compared with the unprotonated form, and this suggests that protonation of
      the tetrapyrrole ring structure has no effect on the overall photochemistry.

PMID- 15446740
TI  - Electrochemical deposition of platinum nanoparticles on carbon: a study by
      standard and anomalous X-ray diffraction.
AB  - This paper is devoted to an alternative method to characterize platinum
      nanoparticles: X-ray powder diffraction with synchrotron radiation in classical
      and anomalous dispersion modes. We could straightforwardly determine the mean
      diameter and the surface concentration of carbon-supported platinum
      nanoparticles, even down to diameters of 2-3 nm and catalyst amounts of 0.03
      mgcm(-2). We could study early stages of the formation of electrochemically
      prepared platinum nanoparticles from [PtCl4(2-) species preadsorbed on carbon
      inside a carbon-Nafion layer, to obtain a fuel-cell electrode. Our X-ray
      diffraction (XRD) results demonstrate that, provided the superficial
      concentration is not too high, new and smaller particles appear for each current
      pulse, since there is not any strong nucleation limitation for the high
      overvoltages obtained. Hydrogen evolution becomes the main electrochemical
      phenomenon on particles of sufficient size and it explains the noteworthy size
      limitation. Better yields of Pt metal are obtained for smaller current densities
      and longer times: the rate-determining step is then not electrochemical, but
      chemical or related to superficial diffusion.

PMID- 15446741
TI  - Adsorption of amyloid beta (1-40) peptide to phosphatidylethanolamine monolayers.
AB  - The aggregation of soluble, nontoxic amyloid beta (Abeta) peptide to beta-sheet
      containing fibrils is assumed to be a major step in the development of
      Alzheimer's disease. Interactions of Abeta with neuronal membranes could play a
      key role in the pathogenesis of the disease. Herein, we study the adsorption of
      synthetic Abeta peptide to DPPE and DMPE monolayers (dipalmitoyl- and
      dimyristoylphosphatidylethanolamine). Both lipids exhibit a condensed monolayer
      state at 20 degrees C and form a similar lattice. However, at low packing
      densities (at large area per molecule), the length of the acyl chains determines
      the phase behavior, therefore DPPE is fully condensed whereas DMPE exhibits a
      liquid-expanded state with a phase transition at approximately 5-6 mNm(-1).
      Adsorption of Abeta to DPPE and DMPE monolayers at low surface pressure leads to
      an increase of the surface pressure to approximately 17 mNm(-1). The same was
      observed during adsorption of the peptide to a pure air-water interface. Grazing
      incidence X-ray diffraction (GIXD) experiments show no influence of Abeta on the
      lipid structure. The adsorption kinetics of Abeta to a DMPE monolayer followed by
      IRRAS (infrared reflection absorption spectroscopy) reveals the phase transition
      of DMPE molecules from liquid-expanded to condensed states at the same surface
      pressure as for DMPE on pure water. These facts indicate no specific interactions
      of the peptide with either lipid. In addition, no adsorption or penetration of
      the peptide into the lipid monolayers was observed at surface pressures above 30
      mNm(-1). IRRAS allows the measurement of the conformation and orientation of the
      peptide adsorbed to the air-water interface and to a lipid monolayer. In both
      cases, with lipids at surface pressures below 20 mNm(-1) and at the air-water
      interface, adsorbed Abeta has a beta-sheet conformation and these beta-sheets are
      oriented parallel to the interface.

PMID- 15446742
TI  - The state of the iron promoter in tungstated zirconia catalysts.
AB  - The activity and selectivity of tungstated zirconia (WZ) for the conversion of n-
      into isopentane are dramatically enhanced when the catalyst is modified with Pt
      and Fe. The state of iron in these catalysts was hitherto only poorly
      characterized. Therefore, in the present work we investigated the structural and
      electronic properties of iron in WZ catalysts containing 1 wt% Pt and 1 wt%
      Fe2O3, by a combination of spectroscopic techniques, namely X-ray absorption
      spectroscopy (XAS), in situ electron paramagnetic resonance (EPR), and Mossbauer
      spectroscopy. In the oxidized catalyst, iron is present as Fe(III) and
      predominantly forms a surface solid solution in which the isolated Fe(III) ions
      are located in a distorted octahedral environment. A small amount of the total
      iron (around 10%) is present in the form of small iron oxide particles. Both iron
      species can be reduced in H2 and then easily reoxidized on exposure to air at
      room temperature. We infer that the promoter action of iron in these catalysts is
      intimately related to its redox properties and specifically affects the
      dehydrogenation activity of the materials.

PMID- 15446743
TI  - A novel fluorophore with dual fluorescence: local excited state and photoinduced
      electron-transfer-promoted charge-transfer state.
AB  - Absorption and emission spectra of 9-N,N-dimethylaniline decahydroacridinedione
      (DMAADD) have been studied in different solvents. The fluorescence spectra of
      DMAADD are found to exhibit dual emission in aprotic solvents and single emission
      in protic solvents. The effect of solvent polarity and viscosity on the
      absorption and emission spectra has also been studied. The fluorescence
      excitation spectra of DMAADD monitored at both the emission bands are different.
      The presence of two different conformation of the same molecule in the ground
      state has lead to two close lying excited states, local excited (LE) and charge
      transfer (CT), and thereby results in the dual fluorescence of the dye. A CTstate
      involving the N,N-dimethylaniline group and the decahy droacridinedione
      chromophore as donor and acceptor, respectively, has been identified as the
      source of the long wavelength anomalous fluorescence. The experimental studies
      were supported by ab initio time dependent-density functional theory (TDDFT)
      calculations performed at the B3LYP/6-31G* level. The molecule possesses
      photoinduced electron transfer (PET) quenching in the LE state, which is
      confirmed by the fluorescence lifetime and fluorescent intensity enhancement in
      the presence of transition metal ions.

PMID- 15446744
TI  - Self-assembly and characterization of hydrogen-bond-induced nanostructure
      aggregation.
AB  - A supramolecular system of a perylene derivative containing bis(2,6
      diacylaminopyridine) units and a perylene bisimide bound through three hydrogen
      bonds was synthesized and characterized. 1H NMR spectra confirmed the existence
      of hydrogen-bonding interactions between the perylene derivative (3) and the
      perylene bisimide (7). The photocurrent generation of the self-assembled 3.7 film
      was measured, and a cathodic photocurrent response was obtained. SEM images
      indicated that well-defined long fibers could be fabricated by self-assembly, by
      exploiting the hydrogen bonding interactions and pi-pi stacking interactions of
      perylene rings.

PMID- 15446745
TI  - Reaction of para-hydroxy-substituted diphenylmethanes with tert-butoxy radical.

PMID- 15446746
TI  - Effect of pH and alkaline metal cations on the voltammetry of pt(111) single
      crystal electrodes in sulfuric acid solution.

PMID- 15446747
TI  - Unusual redox catalysis in a ruthenium oxide-Prussian blue combined material.

PMID- 15446748
TI  - Formation and decomposition of phenylvinylperoxy radicals in the reaction:
      C6H5C2H2 + O2.

PMID- 15446749
TI  - Experimental validation of Marcus theory for outer-sphere heterogeneous electron
      transfer reactions: the oxidation of substituted 1,4-phenylenediamines.

PMID- 15446750
TI  - First direct observation of the higher triplet excited states of substituted
      oligothiophenes by two-color two-laser flash photolysis.

PMID- 15446751
TI  - Application of hole theory to the viscosity of ionic and molecular liquids.

PMID- 15446752
TI  - Novel lipid nanotubes in dispersions of DMPC.

PMID- 15446753
TI  - The usefulness of the NHS Economic Evaluation Database to researchers undertaking
      technology assessment reviews.
AB  - OBJECTIVES: Health-care technology reviews now increasingly include outcome costs
      as well as clinical effects. This study reports the findings and implications of
      a survey to explore the usefulness of the National Health Service Economic
      Evaluation Database (NHS EED) within this process. METHODS: Postal survey of lead
      authors of Technology Assessment Reviews (TARs) commissioned by the United
      Kingdom's National Institute for Clinical Excellence (NICE). The questionnaire
      investigated the usefulness of NHS EED in terms of (a) search strategy, (b) data
      extraction, (c) quality assessment, and (d) determining requirements for new
      modeling studies. Qualitative data were requested, including opinions regarding
      NHS EED. RESULTS: NHS EED was used in 90 percent of all identified reviews (n =
      46). The questionnaire response rate was 63 percent. The percentage of scores 3
      or above (most useful), 2 or below (least useful), or N/A were, respectively, (a)
      search strategy= 62 percent, 23 percent, 15 percent; (b) data extraction = 23
      percent, 27 percent, 50 percent, (c) quality assessment= 38 percent, 19 percent,
      42 percent; (d) determining requirements for new modeling studies = 27 percent,
      23 percent, 50 percent. The results were expanded further in the qualitative data
      from the respondents. CONCLUSIONS: NHS EED is a useful tool for a variety of
      tasks in the NICE/TAR process but not, unsurprisingly, as a replacement for
      understanding primary studies. There is, however, a need to reduce the impact of
      time lags between the publication of economic evaluations and the appearance of
      abstracts relating to them on NHS EED. The results will inform future
      developments of the NHS EED database, which should increase its usefulness to
      researchers.

PMID- 15446754
TI  - Systematic review of the effectiveness of home versus hospital or satellite unit
      hemodialysis for people with end-stage renal failure.
AB  - BACKGROUND: Home hemodialysis offers potential advantages over hospital
      hemodialysis, including the opportunity for more frequent and/or longer dialysis
      sessions. Expanding home hemodialysis services may help cope with the increasing
      numbers of people requiring hemodialysis. METHODS: We sought comparative studies
      or systematic reviews of home versus hospital/satellite unit hemodialysis for
      people with end-stage renal failure (ESRF). Outcomes included quality of life and
      survival. We searched MEDLINE, EMBASE, HealthSTAR, CINAHL, PREMEDLINE, and
      BIOSIS. Two reviewers independently extracted data and assessed the quality of
      the studies included. RESULTS: Twenty-seven studies of variable quality were
      included. People on home hemodialysis generally experienced a better quality of
      life and lived longer than those on hospital hemodialysis. Their partners,
      however, found home hemodialysis more stressful. Four studies using a Cox
      proportional hazards model to compare home with hospital hemodialysis reported a
      lower mortality risk for home hemodialysis. Of two studies using a Cox model to
      compare home with satellite unit hemodialysis, one reported a similar mortality
      risk, whereas the other reported a lower mortality risk for home hemodialysis.
      CONCLUSIONS: Home hemodialysis was generally associated with better outcomes than
      hospital hemodialysis and (more modestly so) satellite unit hemodialysis, in
      terms of quality of life, survival, and other measures of effectiveness. People
      on home hemodialysis, however, are a highly selected group. Home hemodialysis
      also provides the opportunity for more frequent and/or longer dialysis sessions
      than would otherwise be possible. It is difficult to disentangle the true effects
      of home hemodialysis from such influencing factors.

PMID- 15446755
TI  - Cost-effectiveness of reduction mammaplasty.
AB  - OBJECTIVES: The purpose of this study is to provide a comparison of the benefits
      of reduction mammaplasty (RM) for women with heavy breasts often termed
      macromastia or breast hypertrophy (BH) surgery. The rationale is to provide
      information to allow decision-makers to make judgments about the cost
      effectiveness of this intervention and make comparisons with other interventions
      which are commonly undertaken within publicly financed health-care systems.
      METHODS: Data from a previous outcomes study in Sweden is re-analyzed to derive
      quality of life measures, from which a mean level of benefit outcome is derived
      and a cost per quality-adjusted life year is calculated (cost per QALY). RESULTS:
      The low Cost per QALY suggests that reduction mammaplasty is cost-effective when
      compared with other treatments which are commonly undertaken. CONCLUSIONS: The
      authors suggest that the evidence in favor of funding reduction mammaplasty is
      strong and that decision-makers review their policy in light of this new
      evidence.

PMID- 15446756
TI  - Management for severe Crohn's disease: a lifetime cost-utility analysis.
AB  - OBJECTIVES: Infliximab is a costly therapy for active Crohn's disease resistant
      to corticosteroids and immunosuppressive medication. The purpose of this study
      was to examine whether a treatment including infliximab (episodic re-infusions
      for relapse or maintenance therapy every 8 weeks) was relevant compared with
      conventional management (surgery and medical treatment without infliximab) for
      nonfistulizing resistant Crohn's disease. METHODS: We performed a life-time cost
      utility analysis with an analytic Markov decision model from the perspective of
      the third-party payer system. Utility measurement using Standard Gamble was used
      to adjust the survival time for each health state of the disease. Direct costs
      were estimated from standard management based on expert opinion. A sensitivity
      analysis was conducted to gauge the effects of uncertainty in the values assigned
      to variables. RESULTS: The incremental effectiveness with infliximab therapy is
      .761 Quality-Adjusted Life Years (QALYs) for an added cost ranging from 48,478.79
      euros to 596,990.35 euros, depending on treatment procedure. The incremental cost
      utility ratio expressed in euros per QALYs saved varied from 63,700.82 euros
      (episodic re-infusions) to over 762,245.09 euros (maintenance therapy).
      CONCLUSIONS: Infliximab therapy could be cost-effective in the case of relapse
      treatment only, whereas the marginal cost-utility ratio exceeds conventional
      benchmarks for maintenance therapy. This analysis will be supplemented by
      conducting further randomized controlled trials and prospective observational
      study, focused on the costs of illness (direct and indirect), patient
      preferences, the disease's clinical course, and infliximab safety.

PMID- 15446757
TI  - Assessing the economics of vaccination for Neisseria meningitidis in
      industrialized nations: a review and recommendations for further research.
AB  - OBJECTIVES: To review the existing health economic literature on meningococcal
      disease vaccination. METHODS: A Medline search for economic evaluations of
      vaccination programs for meningococcal disease in developed countries was
      conducted. All identified studies were reviewed. RESULTS: Nine published studies
      were identified examining either mass vaccination during outbreaks or routine
      vaccination. Although net expenses were estimated in almost all studies, the
      resulting cost-effectiveness ratios varied widely. Vaccination of college-age
      students was found to be potentially cost-effective in Australia but not in the
      United States. With one exception, routine vaccination of children and
      adolescents in Europe was predicted to be cost-effective. Many simplifying
      assumptions were made, and important elements were often left out, in particular
      the potential for reduced transmission of disease. CONCLUSIONS: The methods used
      and the vaccination strategies vary widely, and results do not provide strong
      grounds for making conclusions as to whether vaccination is cost-effective.
      Furthermore, in all instances, transmission of disease, changes in population
      carriage rates, and outbreaks are either ignored, dealt with using very broad
      simplifying assumptions, or are not necessarily generalizable to other settings.
      The analyses provide some insight into the potential cost-effectiveness of
      vaccination, but more importantly, they highlight areas requiring further study.
      Economic evaluations based on observed outcomes from recently implemented
      strategies would be helpful, as would more sophisticated health economic models.
      The choice of vaccination strategies cannot be based on the results of existing
      economic analyses.

PMID- 15446758
TI  - Using decision modeling to determine pricing of new pharmaceuticals: the case of
      neurokinin-1 receptor antagonist antiemetics for cancer chemotherapy.
AB  - OBJECTIVES: Decision analysis is commonly used to perform economic evaluations of
      new pharmaceuticals. The outcomes of such studies are often reported as an
      incremental cost per quality-adjusted life year (QALY) gained with the new agent.
      Decision analysis can also be used in the context of estimating drug cost before
      market entry. The current study used neurokinin-1 (NK-1) receptor antagonists, a
      new class of antiemetics for cancer patients, as an example to illustrate the
      process using an incremental cost of dollars Can20,000 per QALY gained as the
      target threshold. METHODS: A decision model was developed to simulate the control
      of acute and delayed emesis after cisplatin-based chemotherapy. The model
      compared standard therapy with granisetron and dexamethasone to the same protocol
      with the addition of an NK-1 before chemotherapy and continued twice daily for
      five days. The rates of complete emesis control were abstracted from a double
      blind randomized trial. Costs of standard antiemetics and therapy for
      breakthrough vomiting were obtained from hospital sources. Utility estimates
      characterized as quality-adjusted emesis-free days were determined by
      interviewing twenty-five oncology nurses and pharmacists by using the Time Trade
      Off technique. These data were then used to estimate the unit cost of the new
      antiemetic using a target threshold of dollars Can20,000 per QALY gained.
      RESULTS: A cost of dollars Can6.60 per NK-1 dose would generate an incremental
      cost of dollars Can20,000 per QALY. The sensitivity analysis on the unit cost
      identified a range from dollars Can4.80 to dollars Can10.00 per dose. For the
      recommended five days of therapy, the total cost should be dollars Can66.00
      (dollars Can48.00-dollars Can100.00) for optimal economic efficiency relative to
      Canada's publicly funded health-care system. CONCLUSIONS: The use of decision
      modeling for estimating drug cost before product launch is a powerful technique
      to ensure value for money. Such information can be of value to both drug
      manufacturers and formulary committees, because it would facilitate negotiations
      for optimal pricing in a given jurisdiction.

PMID- 15446759
TI  - Retrieval of missing data for meta-analysis: a practical example.
AB  - OBJECTIVES: To examine the feasibility of retrieving missing outcome data for
      summary meta-analyses using an example dealing with the effects of aerobic
      exercise on lipids and lipoproteins in adults. METHODS: Missing lipid and/or
      lipoprotein data from a currently developed meta-analytic data base were
      requested by means of electronic mail from 39 of 174 (22.4 percent) eligible
      studies. Binary logistic regression was used to examine whether year of
      publication and country were significant predictors for whether data would be
      provided. RESULTS: Of the thirty-nine studies from which data were requested,
      usable data were received for thirteen (33.3 percent) of the studies. The
      addition of these previously missing data decreased the percentage of eligible
      studies that would have had to be excluded by 33.5 percent (from 22.4 percent to
      14.9 percent). Neither year of publication nor country in which the study was
      conducted (United States versus other) were significant predictors of whether
      missing data would be provided or not (p > .05). CONCLUSIONS: Moderate success
      was achieved in the acquisition of missing outcome data dealing with the effects
      of aerobic exercise on lipids and lipoproteins in adults. However, whether this
      level of response is true in other areas of research needs to be determined by
      additional research.

PMID- 15446760
TI  - Cross-national comparison of technology assessment processes.
AB  - OBJECTIVES: To compare methods and results among four health technology
      assessment organizations in different countries. METHODS: All assessment reports
      published between 1999 and 2001 by VATAP (United States), NICE (United Kingdom),
      CCOHTA (Canada), and AETS (Spain), were reviewed. Detailed information about the
      organization, the technology assessed, the methods used, and the recommendations
      made were collected. A descriptive analysis of the variables, as well as
      comparisons of means and proportions, was performed. RESULTS: Sixty-one reports
      assessing seventy-six technologies were published: nine (11.8 percent) by VATAP,
      thirty-nine (51.3 percent) by NICE, twenty (26.3 percent) by CCOHTA, and eight
      (10.5 percent) by AETS. A total of 64.5 percent of the technologies assessed were
      related to a high prevalence disease in the corresponding country. Most of the
      assessments addressed treatments (73.7 percent) and were mostly drugs (56.6
      percent) and devices (23.7 percent). Most organizations used reviews of
      effectiveness and economic evaluations (64.5 percent), systematic reviews (21.1
      percent), and original economic evaluations (36.7 percent). In 38.1 percent, the
      technology was recommended; the rest of the cases had no formal recommendations.
      CONCLUSIONS: Critical issues for future technology assessment efforts are making
      assessment processes more consistent, transparent, and evidence-based;
      formalizing the inclusion of economic and ethical considerations; and making more
      explicit the prioritization process for selecting technologies for assessment and
      reassessment.

PMID- 15446761
TI  - EMEA and the evaluation of health-related quality of life data in the drug
      regulatory process.
AB  - OBJECTIVES: This study reviewed the European guidelines of the Committee for
      Proprietary Medicinal Products (CPMP) on how health-related quality of life
      (HRQOL) research should be conducted in clinical trials. Published product-level
      information was also reviewed to investigate the actual role of HRQOL data in the
      European regulatory process. METHODS: All disease-specific notes for guidance and
      concept papers on clinical investigations, development and evaluation of human
      medicinal products, as well as the European Public Assessment Reports (EPAR) of
      all approved drugs published on the European Agency for the Evaluation of
      Medicinal Products (EMEA) Web site were evaluated for their HRQOL
      recommendations. RESULTS: Only twenty of the fifty CPMP guidance notes for
      clinical investigation of pharmaceutical products in specific disease areas
      included a reference to HRQOL. Most of the recommendations were generic and
      vague, and the terminology used was inconsistent across documents. The EPAR
      provided nonspecific information about HRQOL and contradictory conclusions on the
      effect of a drug on HRQOL sometimes occurred in different documents. The criteria
      used by the CPMP to assess the HRQOL data could not be identified due to an ad
      hoc approach to the inclusion of data in the EPAR. CONCLUSIONS: A more systematic
      approach is needed on the way health outcomes data are considered, reviewed, and
      interpreted by the regulatory authorities. For this to be achieved, CPMP should
      develop general guidelines on the importance of HRQOL and how research should be
      conducted if data are to be included in the registration process.

PMID- 15446762
TI  - Redefining health technology assessment in Canada: diversification of products
      and contextualization of findings.
AB  - OBJECTIVES: While strategies for enhancing the dissemination and impact of Health
      Technology Assessment (HTA) are now being increasingly examined, the
      characteristics of HTA production have received less attention. METHODS: This
      study presents the results of a content analysis of the HTA documents (n = 187)
      produced by six Canadian agencies from 1995 to 2001, supplemented by interviews
      with chief executive officers and researchers (n = 40). The goal of this analysis
      was to characterize the agencies' portfolios and to analyze the challenges these
      agencies face in responding to the increased demand for HTA. RESULTS: On average,
      thirty HTA products were issued annually by the agencies. While the bulk of
      documents produced were full HTA reports (76 percent), two agencies showed
      significant diversification in their products. Three agencies in particular
      actively supported the publication of results in scientific journals. Three
      agencies showed evidence of adapting to different institutional environments by
      specializing in certain areas (drugs, health services). Overall, a significant
      portion of the agencies' HTAs contained data on costs (37 percent) and
      effectiveness (48 percent), whereas ethical and social issues were rarely
      addressed (17 percent). Most agencies addressed issues and outcomes that did not
      strictly fall under the typical definition of HTA but that increased the
      "contextualization" of their findings. CONCLUSIONS: Our discussion highlights
      four paradoxes and reflects further on challenges raised by the coordination of
      HTA within large countries and among European states. This study concludes that
      HTA is being redefined in Canada as HTA agencies offer a more contextualized
      informational basis, an approach that may prove more compatible with the
      increased demand for HTA.

PMID- 15446763
TI  - Issues for countries considering introducing the "fourth hurdle": the case of
      Hungary.
AB  - OBJECTIVES: This study outlines the needs and current development of the "fourth
      hurdle" (i.e., requirement of effectiveness and cost-effectiveness data for drug
      coverage policy decisions) in Hungary, describes the legal background and seeks
      to address some of the most important questions in this field. METHODS: The study
      draws on international experiences and discusses five issues that a given
      jurisdiction needs to consider before introducing the "fourth hurdle" for
      pharmaceuticals. RESULTS: The "fourth hurdle" is very relevant in Hungary because
      many existing drugs are unevaluated and many new, expensive drugs are becoming
      available. On the other hand, the existing resources for health technology
      assessment, including economic evaluation, are quite limited. All the five issues
      are relevant in the Hungarian setting and were helpful in determining exactly how
      the "fourth hurdle" should be applied. CONCLUSIONS: The most important issue
      seems to be that the implementation of the "fourth hurdle" needs to be achieved
      in a way consistent with the limited resources for HTA in Hungary. Specifically
      this means that, in setting priorities for drugs to evaluate, additional criteria
      need to be applied. In particular, priority should be given to assessing drugs
      that have been evaluated in other countries, because this affords the opportunity
      to adapt existing studies or models to the Hungarian situation.

PMID- 15446764
TI  - "The future should not take us by surprise": preparation of an early warning
      system in Denmark.
AB  - OBJECTIVES: To explore and test methods for the operation of a national Early
      Warning System (EWS) in Denmark and to support decision making by the Danish
      Centre for Evaluation and Health Technology Assessment on this issue. METHODS: On
      the basis of literature reviews, information from members of EuroScan, and
      supported by clinical experts and stakeholders, existing methods were adapted and
      new methods were developed as part of a feasibility study. RESULTS: Approximately
      200 technologies in 30 specialties were identified on the basis of information by
      EuroScan. A new instrument was developed to distinguish between important and
      unimportant technologies (filtering). Clinical experts in six specialties applied
      the instrument to sixty-two technologies in their respective fields, of which
      nine (15%) were judged potentially important for the Danish health care system.
      For priority setting, adapting a Dutch instrument to the Danish context was
      discussed. In principle, the instrument was acceptable, but several changes were
      proposed, for example, relating to the decentralized structure of the Danish
      health care system. For early assessment, the format and methods applied by SBU
      and Canadian Coordinating Office for Health Technology Assessment (CCOHTA) were
      compared and applied to pharmaceuticals (glitazones in treatment of type 2
      diabetes mellitus) and a procedure (embolization of uterine fibromas). Given the
      main target group of the Danish EWS, local decision makers, the CCOHTA format was
      preferred. CONCLUSIONS: The findings of the study have laid the foundation for an
      EWS using appropriate methods adapted to local circumstances. On the basis of the
      findings, a decision was made to start an EWS.

PMID- 15446765
TI  - Factors influencing the publication of health research.
AB  - OBJECTIVES: Assess the degree to which research project findings were published
      and explore factors that influenced publication. METHODS: Questionnaire to
      project leaders. Classification of publications and findings. Chi-squared;
      univariate and multivariate Cox regression analyses. RESULTS: Forty percent of
      projects published in peer-reviewed journal; highly statistically significant
      relationships between publication in peer-reviewed journals and (1) projects in
      Responsive/Fellowships streams (p = .045); and (2) projects awarded > pounds
      sterling 22,713 (p = .02); influence of study findings not statistically
      significant. CONCLUSIONS: Funders should consider the significant number of
      studies that did not result in publication and the higher rate of publication in
      peer-reviewed journals from some programs.

PMID- 15446766
TI  - Empirical assessment of the impact of drug-eluting stents on the rate of use of
      coronary revascularization procedures.
AB  - OBJECTIVES: To assess the impact of the availability of drug-eluting stents (DES)
      in April 2002 in Emilia-Romagna (a four-million resident Italian region), on the
      rate of use of revascularization procedures. DES are expected to influence the
      rate of use of coronary artery bypass graft (CABG) and percutaneous coronary
      interventions (PCI). However, to date, little empirical information is available
      on the actual impact of this innovation on clinical practice. METHODS: A time
      series regression analysis of the monthly number of procedures (PCI and CABG)
      performed between January 1998 and March 2003. RESULTS: DES availability was
      associated with statistically significant changes in the use of revascularization
      procedures, although the size of the effect was always small or moderate. PCI
      increased only by 0.36 more procedures per month (approximately four per year),
      whereas more evident was the concurrent reduction of isolated CABG (4.15 fewer
      per month, that is fifty fewer per year). Overall, considering all the surgical
      revascularizations (i.e., CAGB both isolated and associated with other
      interventions), there was a reduction of 2.52 procedures per month (thirty less
      per year). CONCLUSIONS: Despite DES being at a very early stage of their
      diffusion process, our results indicate that they are already having an impact,
      although moderate, on the use of revascularization procedures. If these findings
      will be confirmed, they will have a substantial influence on the patterns of care
      for patients with coronary artery disease and relevant policy implications for
      health services.

PMID- 15446767
TI  - Modeling utility of second-eye cataract surgery.
AB  - OBJECTIVES: To study the impact on public health in terms of utility of various
      proportions of first-eye and second-eye cataract surgery. METHODS: A model was
      used to study the impact on a population of a fixed cataract surgical rate (9,250
      operations/1,000,000 people) with varying proportions of first-eye and second-eye
      cataract operations. The study population was the County of Blekinge with a known
      incidence of previous cataract surgery. The prevalence of cataract, the estimated
      need for cataract surgery, and the utility values were taken from the literature.
      The population was grouped by disability stage of cataract and previous cataract
      surgery in accordance with prevalence studies and data from a large national
      database on cataract surgery and patients' self-assessed visual function. The
      mortality rate was taken from real data for the study population. RESULTS: Given
      a fixed cataract surgical rate over a period of five years, a high percentage of
      second-eye cataract surgery (42 percent) resulted in a mean utility of 0.82239 in
      the population forty years of age and older and the corresponding number for a
      low percentage of second-eye cataract surgery (25 percent) was 0.82253. A high
      percentage of second-eye surgeries resulted in 421 more individuals who were well
      compared with a low percentage of second-eye surgeries. On the other hand, a low
      percentage of second-eye surgeries resulted in 152 fewer individuals with
      disability and 118 fewer individuals with dependence compared with a high
      percentage of second-eye surgeries. CONCLUSIONS: A high frequency of first-eye
      cataract surgeries instead of second-eye surgeries affects more individuals and
      means an optimized improvement of utility in a population. This should be
      recommended if the cataract surgical rate is very insufficient. If the cataract
      surgical rate is high, more second-eye surgeries should be performed to optimize
      quality of life to as many as possible.

PMID- 15446768
TI  - Cost-effectiveness of interventions to reduce the thrombolytic delay for acute
      myocardial infarction.
AB  - OBJECTIVES: The objective of the study was to estimate the costs and health
      benefits of a public awareness campaign aimed at shortening the delay for
      thrombolytic therapy in patients with acute myocardial infarction (AMI) and to
      estimate the incremental costs and benefits of an additional telemedicine
      program. METHODS AND RESULTS: By using trial data on the impact of a Swedish
      campaign, a model was developed to simulate the current distribution of
      thrombolytic delay in Denmark and the delay after a campaign. The reduction in
      delay was translated into reduced fatality assuming reductions from the campaign
      and additional effects of a telemedicine program. The costs of the campaign were
      based on trial data and Danish unit costs while telemedicine costs were taken
      from a Danish demonstration program. The analyses indicate that the awareness
      campaign will translate into five fewer fatal AMIs (sixty-two life years gained)
      and a cost per life year of DKK283,300, with both costs and benefits discounted
      at 5 percent. When combining the public campaign with prehospital telemedicine
      diagnostics, the incremental cost per life year gained was DKK854.700.
      CONCLUSIONS: Programs aimed at reducing delay of thrombolysis in patients with
      AMI are likely to have a limited impact on AMI fatality. Information campaigns
      may have acceptable cost-effectiveness ratios, while telemedicine programs lead
      to threefold greater ratios. Whether such programs can be considered cost
      effective will depend on how life year gains are valued by society.

PMID- 15446769
TI  - Cost of stroke in Sweden: an incidence estimate.
AB  - OBJECTIVES: To estimate the excess cost of stroke in Sweden and the potential
      costs that could be avoided by preventing first-ever strokes. METHODS: We adopted
      the incidence approach for estimating the present value of both direct and
      indirect costs. Data on mortality, stroke recurrence, and inpatient care were
      estimated from a national register of patient data with a four-year follow-up
      period. To estimate costs for social services, we used survey data on living
      conditions before stroke onset and at three and at twenty-four months. Costs for
      outpatient visits, rehabilitation, drugs, and production losses due to premature
      death and early retirement were estimated on the basis of both published and
      nonpublished sources. Lifetime costs were based on life tables adjusted for
      excess mortality of stroke, and costs in year 4 were extrapolated to subsequent
      years. RESULTS: The present value direct cost for an average stroke patient is
      SEK513,800 (USdollars 56,024 or Euro60,825). The corresponding indirect cost is
      SEK125,110 (USdollars13,640 or Euro14,810). Almost 45 percent of the direct costs
      were attributable to social services. Women had higher costs than men, and costs
      for survivors increased with age due to social services. CONCLUSIONS: With an
      incidence of 213 first-ever strokes per 100,000 individuals, the total excess
      direct and indirect cost of stroke would be SEK12.3 billion (approximately US$1.3
      billion or Euro1.5 billion). Hence, there are large potential cost offsets both
      in the health-care sector and in the social service sector if the incidence of
      first-ever stroke could be reduced.

PMID- 15446770
TI  - Assessing the accuracy of forecasting: applying standard diagnostic assessment
      tools to a health technology early warning system.
AB  - OBJECTIVES: Early warning systems are an integral part of many health technology
      assessment programs. Despite this finding, to date, there have been no
      quantitative evaluations of the accuracy of predictions made by these systems. We
      report a study evaluating the accuracy of predictions made by the main United
      Kingdom early warning system. METHODS: As prediction of impact is analogous to
      diagnosis, a method normally applied to determine the accuracy of diagnostic
      tests was used. The sensitivity, specificity, and predictive values of the
      National Horizon Scanning Centre's prediction methods were estimated with
      reference to an (imperfect) gold standard, that is, expert opinion of impact 3 to
      5 years after prediction. RESULTS: The sensitivity of predictions was 71 percent
      (95 percent confidence interval [CI], 0.36-0.92), and the specificity was 73
      percent (95 percent CI, 0.64-0.8). The negative predictive value was 98 percent
      (95 percent CI, 0.92-0.99), and the positive predictive value was 14 percent (95
      percent CI, 0.06-0.3). CONCLUSIONS: Forecasting is difficult, but the results
      suggest that this early warning system's predictions have an acceptable level of
      accuracy. However, there are caveats. The first is that early warning systems may
      themselves reduce the impact of a technology, as helping to control adoption and
      diffusion is their main purpose. The second is that the use of an imperfect gold
      standard may bias the results. As early warning systems are viewed as an
      increasingly important component of health technology assessment and decision
      making, their outcomes must be evaluated. The method used here should be
      investigated further and the accuracy of other early warning systems explored.

PMID- 15446771
TI  - Readmission rate as an indicator of hospital performance: the case of Spain.
AB  - OBJECTIVES: Hospital readmission rate is currently used as a quality of care
      indicator, although its validity has not been established. Our aims were to
      identify the frequency and characteristics of potential avoidable readmissions
      and to compare the assessment of quality of care derived from readmission rate
      with other measure of quality (judgment of experts). METHODS:  DESIGN: cross
      sectional observational study; SETTING: acute care hospital located in Marbella,
      South of Spain; STUDY PARTICIPANTS: random sample of patients readmitted at the
      hospital within six months from discharge (n = 363); INTERVENTIONS: review of
      clinical records by a pair of observers to assess the causes of readmissions and
      their potential avoidability; MAIN MEASURES: logistic regression analysis to
      identify the variables from the databases of hospital discharges which are
      related to avoidability of readmissions. Determination of sensitivity and
      specificity of different definitions of readmission rate to detect avoidable
      situations. RESULTS: Nineteen percent of readmissions were considered potentially
      avoidable. Variables related to readmission avoidability were (i) time elapsed
      between index admission and readmission and (ii) difference in diagnoses of both
      episodes. None of the definitions of readmission rate used in this study provided
      adequate values of sensitivity and specificity in the identification of
      potentially avoidable readmissions. CONCLUSIONS: Most readmissions in our
      hospital were unavoidable. Thus, readmission rate might not be considered a valid
      indicator of quality of care.

PMID- 15446772
TI  - Closing the loop of the medication use process using electronic medication
      administration registration.
AB  - Recent reports and studies of errors in the medication process have raised the
      awareness of the threat to public health. An essential step in this multi-stage
      process is the actual administration of a medicine to the patient. The closed
      loop system is thought to be a way of preventing medication errors. Current
      information technology can facilitate this process. This article describes the
      way barcode technology is being used to facilitate medication administration
      registration on several wards in our hospital and nursing home.

PMID- 15446773
TI  - Use of angiotensin receptor antagonists in patients with ACE inhibitor induced
      angioedema.

PMID- 15446774
TI  - The use of the terms 'lifestyle medicines' or 'lifestyle drugs'.
AB  - AIM: over the last 10 decades, 'lifestyle medicines' or 'lifestyle drugs' have
      been used with increasing frequency by journalists, politicians, authorities and
      to some extent by scientists. The objective of this paper is to analyse the
      quantity and quality of the use of these terms and discuss the implications
      associated with the labelling of indications and products as lifestyle medicines
      or lifestyle drugs. METHODS: The findings in this paper are based on an extensive
      literature review in the databases Medline, Pubmed, Embase and the two most
      frequently used search engines altavista.com and google.com, as well as the media
      database LexisNexis. RESULTS: In the period 1978 to August 2003, the term
      'lifestyle medicines/drugs' has appeared 3174 times in English language media. In
      total, 23 different definitions are presented in the scientific literature.
      CONCLUSIONS: The review of the scientific literature shows that no widely
      accepted definition of the terms 'lifestyle medicines' or 'lifestyle drugs'
      exists. Nevertheless the terms have appeared more than 3000 times in the media
      (2600 times since 1998), which means that in most cases, the use of the terms
      'lifestyle medicines' or 'lifestyle drugs' are based on the authors' own
      assumptions and values. This is problematic, not only in terms of a discourse,
      where no one knows what forms the basis of the discussion, but also because this
      at best leads to an uninformed discussion and at worst to harmful conclusions
      that might stigmatise and discriminate patients. Based on these findings, this
      paper argues that a clear, widely accepted definition of the terms 'lifestyle
      medicines' or 'lifestyle drugs' is essential to avoid potential misunderstandings
      that might lead to discrimination in the rationing of healthcare resources or
      stigmatisation of patients.

PMID- 15446775
TI  - Needs and use of drug information sources in community pharmacies: a
      questionnaire based survey in German-speaking Switzerland.
AB  - OBJECTIVES: To explore the types of drug information used by pharmacists in daily
      practice, their needs and wishes concerning drug information and their opinions
      about future changes of pharmacy practice. METHODS: Postal survey to a random
      sample of 223 (26% out of 859) community pharmacies from the German-speaking part
      of Switzerland. The 48-item questionnaires were processed automatically with the
      Cardiff TELEform-Software. In addition, a telephone-survey to a random sample of
      20 non-responders was performed in order to test for non-response bias. RESULTS:
      A total of 108 pharmacists (response rate 48%) reported that the official Swiss
      drug reference book is still the most popular source of drug information used to
      solve all kinds of drug related problems. The Internet as a source of drug
      information is of minor importance, even though 88% of the pharmacies have
      Internet access. Deficits in drug information were reported for paediatrics,
      phytotherapy, drugs during pregnancy/lactation and for therapy guidelines.
      According to 35% of the pharmacists, the importance of offering drug information
      to customers will increase in the future. Most of the pharmacists are not afraid
      that Internet pharmacies would replace them. CONCLUSIONS: The results show that
      the majority of the community pharmacists are only partially satisfied with the
      sources of drug information currently available. The Internet still plays a minor
      role for solving drug-related problems in daily practice, even though the
      available infrastructure makes the community pharmacies able to use the Internet
      more frequently. The pharmacists need more websites tailored to their needs. The
      pharmacists have clear visions about possible future developments. They do,
      however, have to adopt quickly to the changes ahead in order to remain
      competitive.

PMID- 15446776
TI  - The new consumer of medicine--the pharmacy technicians' perspective.
AB  - OBJECTIVE: Market research, and more recently health services research, has
      adopted the concept of the 'new consumer' to describe customers/patients who are
      becoming more demanding. This study aims to determine the relevancee of the
      concept 'new consumer' for pharmacy practice, in light of the theory of 'risk
      society'. METHOD: Qualitative in-depth interviews were carried out with seven
      pharmacy technicians from six different pharmacies in the Copenhagen area,
      Denmark. They were asked to describe developments, over time, in consumer
      behaviour. They were asked to focus on three themes: information, the authority
      of the pharmacy staff, and their predictions of the future pharmacy customer.
      RESULTS: Young customers, particularly parents of pre-school children, as well as
      the chronically ill appeared to share the characteristics associated with the
      'new consumer'. They were: information strong (well-informed) and information
      seeking (inquisitive); asked critical questions; showed a desire to longer
      initiate dialogue; sought counselling and in general no longer blindly accepted
      the authority of the pharmacy staff. CONCLUSION: According to pharmacy
      technicians a 'new consumer' does exist and is visible in community pharmacies in
      Copenhagen. Seen in light of the theory of risk society, we further conclude that
      the behaviour of the 'new consumer' is indicative of an attempt to minimize risk
      of drug therapy.

PMID- 15446777
TI  - The impact of guidelines on long-term asthma care: a study of hospitalised
      patients in Malta.
AB  - OBJECTIVE: To compare actual practice to that recommended in asthma guidelines,
      published in Malta in February 1998, with respect to the management of asthma.
      These were the first national clinical guidelines to be published locally.
      METHOD: A piloted, structured interview was conducted with patients between 14-59
      years who were hospitalised with an admission diagnosis of acute asthma. In the
      case of repeated admissions, only the first interview was considered. All
      interviews were carried out by either of two clinical pharmacists and lasted
      about 30 min. The four-year prospective study started in February 1997 (one year
      before publication of guidelines and aimed at collecting baseline data) and
      finished in January 2001 (three years after publication of the local guidelines).
      MAIN OUTCOME MEASURES: Inhaled steroids on admission. Patient partnership: use of
      a written self-management plan and home peak flow monitoring. Patient compliance
      with inhaled steroids. RESULTS: 304 patients (68% females; mean population age
      33.9 years SD +/- 13.41) were interviewed over the four-year period. The
      difference in proportions test (Z-test) was used to analyse the data comparing
      years 2, 3 and 4 with year 1. No statistical differences were found when
      comparing the groups for inhaled steroid treatment on admission or availability
      of a home peak flow meter. Similarly, no differences were found between groups
      when comparing compliance with inhaled steroids. A statistically significant
      increase in availability of a self-management plan was found over the study
      period (3% in year 1; 1% in year 2; 11% in year 3; 9% in year 4), but the overall
      use of such plans remains disappointingly low. CONCLUSION: With the exception of
      an increased use of self-management plans, there appears to be lack of adherence
      to guidelines with consequent undertreatment of asthma, despite the fact that
      guidelines were published three years ago. This indicates a need to ensure better
      dissemination and implementation strategies to promote adherence. It is suggested
      that the clinical pharmacist is well-placed to promote adherence to guidelines.

PMID- 15446778
TI  - Economic evaluation of enoxaparin for the prevention of venous thromboembolism in
      acutely ill medical patients.
AB  - OBJECTIVE: To conduct an economic evaluation of the prevention of venous
      thromboembolism in acutely ill medical patients. METHOD: We used a previously
      described economic model created in the context of the UK National Health Service
      and applied it to St. Thomas' Hospital, London. A clinical review to determine
      the number of medical admissions that would require thromboprophylaxis at St.
      Thomas' Hospital, based on the inclusion criteria of a medical thromboprophylaxis
      trial (MEDENOX), was conducted. Costs and effectiveness were determined, based on
      the provision of thromboprophylaxis to 2000 medical patients. RESULTS: Comparing
      treatment with low-molecular-weight heparin (enoxaparin, 40 mg once daily),
      unfractionated heparin (5000 IU twice daily), or no prophylaxis, the highest cost
      of thromboprophylaxis was associated with unfractionated heparin (199,000 pounds
      sterling = 4306,000 Euros), compared with enoxaparin (198,000 pounds sterling =
      305,000 Euros) or no prophylaxis (176,000 pounds sterling = 271,000 Euros). The
      model suggested that enoxaparin thromboprophylaxis would result in fewer
      thromboembolic-related events. Using sensitivity analysis, incorporating certain
      St. Thomas'-specific costs showed enoxaparin compared with unfractionated heparin
      or no thromboprophylaxis was cost saving. The cost savings of 65,000 pounds
      sterling ( = 100,000 Euros) and 31,000 pounds sterling ( = 48,000 Euros)
      respectively are based on maximum uptake of thromboprophylaxis. CONCLUSIONS: The
      graded implementation of enoxaparin thromboprophylaxis over a four-year period
      would require funding redistribution. The funding Health Authority would save
      overall but St. Thomas' would require an increase in drug expenditure across the
      clinical directorates of 35,000 pounds sterling ( = 54,000 Euros) after 4 years.

PMID- 15446779
TI  - Effects of a management technician on structured working in Dutch community
      pharmacies.
AB  - OBJECTIVE: To study the effects of 'stepwise working with the help of a
      management technician' on structured working with regard to patient education in
      a sample of Dutch community pharmacies. METHODS: The intervention program
      provided the management technician with knowledge, tools and skills needed for
      the organisation of patient education activities in her community pharmacy.
      Twenty-eight pharmacies were selected for the study. After matching, each
      pharmacy was randomly assigned to either the experimental or control group. In
      the pharmacies of the experimental group, a technician was selected to become the
      management technician. MAIN OUTCOME MEASURES: Pharmacy technicians were assessed
      by means of written questionnaires at baseline and immediately after the
      intervention (12 months). The outcomes were the variables that were directly
      targeted by the intervention, and included technicians' perception of the
      availability of policy plans, support for patient education activities towards
      their implementation, evaluation, and provisions for continuity. RESULTS: After
      12 months, the following indicators for structured working were noted to have
      increased in the experimental group compared to the control group: the
      technicians in the experimental group more often reported an awareness of policy
      plans, less lack of continuity of activities, support and evaluation for
      implementing patient education activities. We also observed that the control
      group had a higher baseline level and the effects on support and evaluation
      showed differences between pharmacies. The observed increases were more
      pronounced in pharmac higher exposure to the intervention, and in the case of
      support and evaluation relevant in this more exposed group. CONCLUSION: We found
      indications for effects of the intervention program, especially in the pharmacies
      with increased exposure. However, results could be influenced by regression to
      the mean, as the control group started with a higher mean than the experimental
      group. We conclude that technicians' participation in the management of patient
      education activities appears to be effective when she has a minimum of hours to
      spend on this task in her pharmacy.

PMID- 15446780
TI  - Pre-randomization decisions and group stratification in a randomized controlled
      trial to improve prescribing.
AB  - OBJECTIVE: To select and evaluate characteristics of primary care practice groups
      relevant for stratification prior to randomization. METHOD: Structured telephone
      interviews and pre- and post-intervention prescription data. SETTING: Additional
      study in an RCT to rationalize prescribing in primary care, addressing groups of
      pharmacists and doctors. Representatives of 61 primary care practice groups in
      the Netherlands. MAIN OUTCOME MEASURES: Identification and evaluation of primary
      care practice group characteristics related to changes in prescribing. These
      characteristics were evaluated by estimation of incidence rate ratios (Poisson
      regression). RESULTS: Of practice groups 40 representatives (66%) participated in
      our study. Three characteristics were found to be most relevant for
      stratification: the purpose of the practice groups (whether they participated in
      information exchange (n = 14) or binding consensus on pharmacotherapy (n = 26)),
      the use of a formulary (22 practice groups did and 18 groups did not) and the use
      of feedback data (22 groups did and 18 groups did not). These characteristics
      strongly modified the effect of the program on prescribing behaviour. While the
      overall effect of the program was to significantly reduce the prescribing of the
      targeted drugs, this change was not consistent in all strata. CONCLUSION:
      Assessment of the characteristics of practice groups made it possible to define
      factors to be used for a stratified randomization of practice groups which in
      retrospect indeed modified the effect of an educational intervention directed to
      change prescribing. Such pre-randomization assessments can be a useful tool in
      interventions designed to improve practice patterns in groups of physicians.

PMID- 15446781
TI  - Evaluation of warfarin dosing by pharmacists for elderly medical in-patients.
AB  - OBJECTIVE: To compare the effectiveness of pharmacists dosing warfarin for in
      patients, in comparison to that of junior doctors, in order to establish the
      value of a pharmacist-controlled in-patient anti-coagulation service. SETTING:
      Brighton and Sussex University Hospitals NHS Trust (BSUH). METHOD: Two wards at
      Brighton General Hospital were under pharmacist-control of warfarin dosing and
      three wards remained under the care of doctors. Data was collected for 11 months
      and a total of 33 patients were recruited into each arm. RESULTS: Pharmacists
      prescribed more appropriate loading and maintenance doses (according to the
      Trust's Prescribing Guidelines) compared to doctors. This resulted in more
      patients reaching their target INR sooner. Documentation of indication, duration
      of treatment and target INR was also much improved compared to medical staff.
      However, more patients (73%) in the doctors' group were within range on discharge
      and at the out-patient clinic (79%), compared to the pharmacists (68% & 61%
      respectively). This could not be explained entirely. Significantly fewer patients
      dosed by pharmacists had episodes of over or under anti-coagulation (91% vs 67%)
      and fewer INR tests were requested (2.3/patient/week) compared to those dosed by
      doctors (2.7). Patients under the control of pharmacists also had fewer adverse
      events (6% vs 12%). One major GI bleed occurred in the doctors' group.
      CONCLUSION: Pharmacist dosing of warfarin for in-patients had a beneficial effect
      on most aspects of anti- coagulation control. This study therefore provides
      further evidence to support the extended role pharmacists can play with the
      benefit of reducing risk, junior doctors' hours and improving patient care.

PMID- 15446782
TI  - Gemcitabine plus vinorelbine chemotherapy regimens: a pharmacokinetic study of
      alternate administration sequences.
AB  - OBJECTIVE: To investigate a possible pharmacokinetic interaction between
      gemcitabine (GEM) and vinorelbine (VNR), when co-administered following the
      alternate sequences GEM-VNR and VNR-GEM. METHODS: Enrolled in this study were 31
      patients with different advanced carcinoma: 9 patients were given GEM (1 h i.v.
      infusion, 1000 mg/m2) followed after 5 min by VNR (10 min i.v. infusion, 25
      mg/m2) (GEM-VNR sequence); 17 patients received VNR followed by GEM (VNR-GEM
      sequence), at the same doses and with the same infusion period; as a control
      group (GEM), 5 patients were given only single-agent gemcitabine (1 h i.v.
      infusion, 1000 mg/m2). RESULTS: GEM serum levels showed higher Cmax and AUC(tot)
      in the VNR-GEM protocol than in the GEM-VNR and GEM groups. The GEM
      pharmacokinetic profile in both schedules showed biphasic elimination, as in
      monotherapy. VNR concentration/time curves showed rapid plasma clearance and wide
      interpatient variability in both sequences. VNR Cmax was higher in the VNR-GEM
      group than in GEM-VNR, while VNR AUC(tot) and Cl(tot) did not differ
      significantly in the two sequences. CONCLUSIONS: Some pk-values were altered for
      both GEM and VNR, following the two alternate protocols. A possible rationale for
      this behaviour is that VNR and GEM may influence each other during liver
      elimination extraction and metabolism.

PMID- 15446783
TI  - Gentamicin usage in newborns--a simple and practical regime.
AB  - OBJECTIVE: To audit the gentamicin usage guidelines due to concerns that it
      resulted in too many sub-therapeutic peak levels, devise a new guideline and re
      audit after change in practise. METHOD: A prospective audit of 50 sets of
      gentamicin levels on the Old Gentamicin Regime was conducted. Desired levels were
      a trough <2 microg/ml and peak between 5-10 microg/ml. These were taken just
      before and one hour after the third dose respectively. Peak levels were found to
      be in the sub-therapeutic range in the majority on this regime. Therefore the New
      Gentamicin Regime was put into practise. A re-audit was conducted of the new
      gentamicin regime and 60 trough levels were taken. Peak levels were taken in only
      20 newborns with the intention of not doing peak levels routinely if these were
      satisfactory and the data were analysed. RESULTS: Although trough levels were
      satisfactory in 98% (49/50), peak levels were sub-therapeutic in 92% (46/50) on
      the old gentamicin regime. Following change in practise to the new gentamicin
      regime trough levels were satisfactory in 96.6% (58/60). We collected 20 peak
      levels and these were satisfactory in 80% (16/20). CONCLUSIONS: The new
      gentamicin usage guideline achieves peak levels in the therapeutic range in the
      majority without any added risk of toxic trough levels. Peak levels need not be
      done routinely in all newborns on the new regime.

PMID- 15446784
TI  - A new ultrasonic transducer for improved contrast nonlinear imaging.
AB  - Second harmonic imaging has provided significant improvement in contrast
      detection over fundamental imaging. This improvement is a result of a higher
      contrast-to-tissue ratio (CTR) achievable at the second harmonic frequency.
      Nevertheless, the differentiation between contrast and tissue at the second
      harmonic frequency is still in many situations cumbersome and contrast detection
      remains nowadays as one of the main challenges, especially in the capillaries.
      The reduced CTR is mainly caused by the generation of second harmonic energy from
      nonlinear propagation effects in tissue, which hence obscures the echoes from
      contrast bubbles. In a previous study, we demonstrated theoretically that the CTR
      increases with the harmonic number. Therefore the purpose of our study was to
      increase the CTR by selectively looking to the higher harmonic frequencies. In
      order to be able to receive these high frequency components (third up to the
      fifth harmonic), a new ultrasonic phased array transducer has been constructed.
      The main advantage of the new design is its wide frequency bandwidth. The new
      array transducer contains two different types of elements arranged in an
      interleaved pattern (odd and even elements). This design enables separate
      transmission and reception modes. The odd elements operate at 2.8 MHz and 80%
      bandwidth, whereas the even elements have a centre frequency of 900 kHz with a
      bandwidth of 50%. The probe is connected to a Vivid 5 system (GE-Vingmed) and
      proper software is developed for driving. The total bandwidth of such a
      transducer is estimated to be more than 150% which enables higher harmonic
      imaging at an adequate sensitivity and signal to noise ratio compared to standard
      medical array transducers. We describe in this paper the design and fabrication
      of the array transducer. Moreover its acoustic properties are measured and its
      performances for nonlinear contrast imaging are evaluated in vitro and in vivo.
      The preliminary results demonstrate the advantages of such a transducer design
      for improved contrast detection.

PMID- 15446785
TI  - Miniature ultrasonic probe construction for minimal access surgery.
AB  - The increasing use of minimal access techniques for surgery has produced a need
      for imaging technologies that can be used during such interventions. Ultrasound
      imaging has the advantage that the probe itself can be interventional.
      Interventional ultrasound probes must be sufficiently small to gain access to the
      surgical site, and any rigid portion must be limited in length to permit adequate
      flexibility. In practice this means the ultrasound probes have to operate at high
      frequencies, and a set of design curves have been produced which relate the
      number of elements and the ultrasound frequency to the probe dimensions for both
      linear and cylindrical array configurations. Constructing high-frequency sub
      miniature probes presents a number of technical challenges, in particular
      relating to interconnects and packaging. Solutions to these challenges are
      discussed using the fabrication of a 1 mm diameter intravascular probe as an
      example.

PMID- 15446786
TI  - Effect of area x-ray beam equalization on image quality and dose in digital
      mammography.
AB  - In mammography, thick or dense breast regions persistently suffer from reduced
      contrast-to-noise ratio (CNR) because of degraded contrast from large scatter
      intensities and relatively high noise. Area x-ray beam equalization can improve
      image quality by increasing the x-ray exposure to under-penetrated regions
      without increasing the exposure to other breast regions. Optimal equalization
      parameters with respect to image quality and patient dose were determined through
      computer simulations and validated with experimental observations on a step
      phantom and an anthropomorphic breast phantom. Three parameters important in
      equalization digital mammography were considered: attenuator material (Z = 13
      92), beam energy (22-34 kVp) and equalization level. A Mo/Mo digital mammography
      system was used for image acquisition. A prototype 16 x 16 piston driven
      equalization system was used for preparing patient-specific equalization masks.
      Simulation studies showed that a molybdenum attenuator and an equalization level
      of 20 were optimal for improving contrast, CNR and figure of merit (FOM =
      CNR2/dose). Experimental measurements using these parameters showed significant
      improvements in contrast, CNR and FOM. Moreover, equalized images of a breast
      phantom showed improved image quality. These results indicate that area beam
      equalization can improve image quality in digital mammography.

PMID- 15446787
TI  - Computed radiography as a gamma ray detector--dose response and applications.
AB  - Computed radiography (CR) can be used for imaging the spatial distribution of
      photon emissions from radionuclides. Its wide dynamic range and good response to
      medium energy gamma rays reduces the need for long exposure times. Measurements
      of small doses can be performed without having to pre-sensitize the computed
      radiography plates via an x-ray exposure, as required with screen-film systems.
      Cassette-based Agfa MD30 and Kodak GP25 CR plates were used in applications
      involving the detection of gamma ray emissions from technetium-99m and iodine
      131. Cassette entrance doses as small as 1 microGy (140 keV gamma rays) produce
      noisy images, but the images are suitable for applications such as the detection
      of breaks in radiation protection barriers. A consequence of the gamma ray
      sensitivity of CR plates is the possibility that some nuclear medicine patients
      may fog their x-rays if the x-ray is taken soon after their radiopharmaceutical
      injection. The investigation showed that such fogging is likely to be diffuse.

PMID- 15446788
TI  - Medical phase contrast x-ray imaging: current status and future prospects.
AB  - The exploitation of phase contrast appears to offer the tantalising possibility
      of creating the biggest change in medical x-ray imaging since the invention of
      computed tomography. A considerable number of experiments performed by
      researchers across four continents have produced some extraordinary images. These
      images have demonstrated greatly enhanced contrast over conventional methods
      revealing soft tissue discrimination at micron scale resolutions. Contrast
      improvements can be achieved at doses rather less than those required by
      conventional x-ray imaging. The use of synchrotrons has revealed the
      possibilities offered by these techniques but unfortunately the application of
      these ideas in a clinical context requires that technology be pushed to its
      limits in a number of areas including x-ray sources, optics and detectors. The
      current state of the art is reviewed.

PMID- 15446789
TI  - A diffusion and T2 relaxation MRI study of the ovine lumbar intervertebral disc
      under compression in vitro.
AB  - The ovine lumbar intervertebral disc is a useful model for the human lumbar disc.
      We present preliminary estimates of diffusion coefficients and T2 relaxation
      times in a pilot MRI study of the ovine lumbar intervertebral disc during
      uniaxial compression in vitro, and identify factors that hamper the ability to
      accurately monitor the temporal evolution of the effective diffusion tensor at
      high spatial resolution.

PMID- 15446790
TI  - Angiogenic response of locally advanced breast cancer to neoadjuvant chemotherapy
      evaluated with parametric histogram from dynamic contrast-enhanced MRI.
AB  - The aim of this study was to evaluate angiogenic compositions and tumour response
      in the course of neoadjuvant chemotherapy in patients with locally advanced
      breast cancer (LABC) using dynamic contrast-enhanced (DCE) MRI. Thirteen patients
      with LABC underwent serial DCE MRI during the course of chemotherapy. DCE MRI was
      quantified using a two-compartment model on a pixel-by-pixel basis. Analysis of
      parametric histograms of amplitude, exchange rate k(out) and peak enhancement
      over the whole tumour was performed. The distribution patterns of histograms were
      correlated with the tumour response. Initial kurtosis and standard deviation of
      amplitude before chemotherapy correlated with tumour response, r = 0.63 and r =
      0.61, respectively. Comparing the initial values with the values after the first
      course of chemotherapy, tumour response was associated with a decrease in
      standard deviation of amplitude (r = 0.79), and an increase in kurtosis and a
      decrease in standard deviation of k(out) (r = 0.57 and 0.57, respectively).
      Comparing the initial values with the values after completing the chemotherapy,
      tumours with better response were associated with an increase in kurtosis (r =
      0.62), a decrease in mean (r = 0.84) and standard deviation (r = 0.77) of
      amplitude, and a decrease in mean of peak enhancement (r = 0.71). Our results
      suggested that tumours with better response tended to alter their internal
      compositions from heterogeneous to homogeneous distributions and a decrease in
      peak enhancement after chemotherapy. Serial analyses of parametric histograms of
      DCE MRI-derived angiogenic parameters are potentially useful to monitor the
      response of angiogenic compositions of a tumour throughout the course of
      chemotherapy, and might predict tumour response early in the course.

PMID- 15446791
TI  - Identification of second harmonic optical effects from vaccine coated gold
      microparticles.
AB  - This study investigates the optical effects observed from uncoated and protein
      vaccine coated gold microparticles while imaging with two-photon excitation in
      the Mie scattering regime. When observed with time correlated single photon
      counting fluorescence lifetime microscopy, the emission from the gold
      microparticles appeared as an intense instrument-limited temporal response. The
      intensity of the emission showed a second-order dependence on the laser power and
      frequency doubling of the emitted light was observed for fundamental light
      between 890 and 970 nm. The optical effect was attributed to two-photon induced
      second harmonic generation. The vaccine coated gold microparticles had a much
      weaker second harmonic signal than the uncoated gold microparticles. Chemical
      analysis of the surface of the gold microparticles revealed that the vaccine
      coating decreases the surface charge thereby diminishing the observed second
      harmonic signal. These optical properties can be exploited to identify both the
      location of the protein vaccine coating as well as the gold microparticles in
      vitro and potentially to investigate the vaccine delivery kinetics in vivo.

PMID- 15446792
TI  - Multiple sources of passive stress relaxation in muscle fibres.
AB  - The forces developed during stretch of nonactivated muscle consist of velocity
      sensitive (viscous/viscoelastic) and velocity-insensitive (elastic) components.
      At the myofibrillar level, the elastic-force component has been described in
      terms of the entropic-spring properties of the giant protein titin, but entropic
      elasticity cannot account for viscoelastic properties, such as stress relaxation.
      Here we examine the contribution of titin to passive stress relaxation of
      isolated rat-cardiac myofibrils depleted of actin by gelsolin treatment. Monte
      Carlo simulations show that, up to approximately 5 s after a stretch, the time
      course of stress relaxation can be described assuming unfolding of 1-2
      immunoglobulin domains per titin molecule. For extended periods of stress
      relaxation, the simulations failed to correctly describe the myofibril data,
      suggesting that in situ, titin-Ig domains may be more stable than predicted in
      earlier single-molecule atomic-force-microscopy studies. The reasons behind this
      finding remain unknown; simply assuming a reduced unfolding probability of
      domains--an effect found here by AFM force spectroscopy on titin-Ig domains in
      the presence of a chaperone, alpha-B-crystallin--did not help correctly simulate
      the time course of stress relaxation. We conclude that myofibrillar stress
      relaxation likely has multiple sources. Evidence is provided that in intact
      myofibrils, an initial, rapid phase of stress relaxation results from viscous
      resistance due to the presence of actin filaments.

PMID- 15446793
TI  - Intensity-modulated radiation therapy: overlapping co-axial modulated fields.
AB  - The Varian multi-leaf collimator has a 14.5 cm leaf extension limit from each
      carriage. This means the target volumes in the head and neck region are sometimes
      too wide for standard width-modulated fields to provide adequate dose coverage. A
      solution is to set up asymmetric co-axial overlapping fields. This protects the
      MLC carriage while in return the MLC provides modulated dose blending in the
      field overlap region. Planar dose maps for coincident fields from the Pinnacle
      radiotherapy treatment planning system are compared with planar dose maps
      reconstructed from radiographic film and electronic portal images. The film and
      portal images show small leaf-jaw matchlines at each field overlap border. Linear
      profiles taken across each image show that the observed leaf-jaw matchlines from
      the accelerator images are not accounted for by the treatment planning system.
      Dose difference between film reconstructed electronic portal images and planning
      system are about 2.5 cGy in a modulated field at d(max). While the magnitude of
      the dose differences are small improved round end leaf modelling combined with a
      finer dose calculation grid may minimize the discrepancy between calculated and
      delivered dose.

PMID- 15446794
TI  - Monte Carlo as a four-dimensional radiotherapy treatment-planning tool to account
      for respiratory motion.
AB  - Four-dimensional (4D) radiotherapy is the explicit inclusion of the temporal
      changes in anatomy during the imaging, planning and delivery of radiotherapy.
      Temporal anatomic changes can occur for many reasons, though the focus of the
      current investigation was respiration motion for lung tumours. The aims of the
      current research were first to develop a 4D Monte Carlo methodology and second to
      apply this technique to an existing 4D treatment plan. A 4D CT scan consisting of
      a series of 3D CT image sets acquired at different respiratory phases was used.
      Deformable image registration was performed to map each CT set from the end
      inhale respiration phase to the CT image sets corresponding with subsequent
      respiration phases. This deformable registration allowed the contours drawn on
      the end-inhale CT to be automatically drawn on the other respiratory phase CT
      image sets. A treatment plan was created on the end-inhale CT image set and then
      automatically created on each of the 3D CT image sets corresponding with
      subsequent respiration phases, based on the beam arrangement and dose
      prescription in the end-inhale plan. Dose calculation using Monte Carlo was
      simultaneously performed on each of the N (=8) 3D image sets with 1/N fewer
      particles per calculation than for a 3D plan. The dose distribution from each
      respiratory phase CT image set was mapped back to the end-inhale CT image set for
      analysis. This use of deformable image registration to merge all the
      statistically noisy dose distributions back onto one CT image set effectively
      yielded a 4D Monte Carlo calculation with a statistical uncertainty equivalent to
      a 3D calculation, with a similar calculation time for the 3D and 4D methods.
      Monte Carlo as a dose calculation tool for 4D radiotherapy planning has two
      advantages: (1) higher accuracy for calculation in electronic disequilibrium
      conditions, such as those encountered during lung radiotherapy, and (2) if
      deformable image registration is used, the calculation time for Monte Carlo is
      independent of the number of 3D CT image sets constituting a 4D CT, unlike other
      algorithms for which the calculation time scales linearly with the number of 3D
      CT image sets constituting a 4D CT.

PMID- 15446795
TI  - Prostate implant evaluation using tumour control probability--the effect of input
      parameters.
AB  - In this paper, we examine the effect of treatment parameters in a model used to
      evaluate permanent prostate implants. The model considers the prostate to be
      composed of 12 sub-sections, each sub-section is assigned a cell density based on
      the probability of finding cancer foci in that sub-section. Wasted dose as a
      result of the dose rate from the implant falling below a level adequate to
      counteract repopulation was found to vary by 2-16% over the range of
      radiosensitivity and repopulation rates considered. Within the model, applied to
      five dose distributions, the uncertainty in the tumour control probability (TCP)
      values calculated for each sub-section as a result of differences in the model
      parameters, was found to be less than 12% in most cases for the good quality
      implants. The difference in TCP values was much larger for the poor quality
      implant. Substituting a heterogeneous distribution of alpha for a single mean
      value resulted in generally lower TCP values though introducing a cutoff value
      with a Gaussian distribution had a profound effect on the calculated values.
      Despite uncertainties in the parameters, the model was able to identify sub
      sections at risk of local recurrence but as a result of these uncertainties, the
      TCP values can only be considered in the relative rather than absolute sense.

PMID- 15446796
TI  - Interpolation and extrapolation of dose measurements with different detector
      sizes to improve the spatial resolution of radiotherapy dosimetry as demonstrated
      for helical tomotherapy.
AB  - A new technique for intensity modulated radiation therapy (IMRT) delivery is
      helical tomotherapy (HT). Like most IMRT delivery methods, HT utilizes many small
      fields as part of the treatment plan, which can be difficult to characterize. A
      novel technique for small field characterization, based on inter- and
      extrapolation of ion chamber readings, is presented in the context of HT. As a
      fan beam is characterized by its thickness and output factor, plane parallel
      chambers with different active volumes were used to scan the fan beam profiles.
      The fan beam thickness (FBT) can be determined from the thickness measured with
      the chamber by extrapolating to an infinitesimally small chamber size. The
      effective output was derived from the integral under the dose profile divided by
      the FBT. This was done for five FBTs and demonstrated a sharp fall off in dose
      when the FBT decreased below 8 mm. Similar techniques can be applied to other
      IMRT techniques to improve the characterization of various beam parameters.

PMID- 15446797
TI  - Planning evaluation of radiotherapy for complex lung cancer cases using helical
      tomotherapy.
AB  - Lung cancer treatment is one of the most challenging fields in radiotherapy. The
      aim of the present study was to investigate what role helical tomotherapy (HT), a
      novel approach to the delivery of highly conformal dose distributions using
      intensity-modulated radiation fan beams, can play in difficult cases with large
      target volumes typical for many of these patients. Tomotherapy plans were
      developed for 15 patients with stage III inoperable non-small-cell lung cancer.
      While not necessarily clinically indicated, elective nodal irradiation was
      included for all cases to create the most challenging scenarios with large target
      volumes. A 2 cm margin was used around the gross tumour volume (GTV) to generate
      primary planning target volume (PTV2) and 1 cm margin around elective nodes for
      secondary planning target volume (PTV1) resulting in PTV1 volumes larger than
      1000 cm3 in 13 of the 15 patients. Tomotherapy plans were created using an
      inverse treatment planning system (TomoTherapy Inc.) based on
      superposition/convolution dose calculation for a fan beam thickness of 25 mm and
      a pitch factor between 0.3 and 0.8. For comparison, plans were created using an
      intensity-modulated radiation therapy (IMRT) approach planned on a commercial
      treatment planning system (TheraplanPlus, Nucletron). Tomotherapy delivery times
      for the large target volumes were estimated to be between 4 and 19 min. Using a
      prescribed dose of 60 Gy to PTV2 and 46 Gy to PTV1, the mean lung dose was 23.8+/
      4.6 Gy. A 'dose quality factor' was introduced to correlate the plan outcome with
      patient specific parameters. A good correlation was found between the quality of
      the HT plans and the IMRT plans with HT being slightly better in most cases. The
      overlap between lung and PTV was found to be a good indicator of plan quality for
      HT. The mean lung dose was found to increase by approximately 0.9 Gy per percent
      overlap volume. Helical tomotherapy planning resulted in highly conformal dose
      distributions. It allowed easy achievement of two different dose levels in the
      target simultaneously. As the overlap between PTV and lung volume is a major
      predictor of mean lung dose, future work will be directed to control of margins.
      Work is underway to investigate the possibility of breath-hold techniques for
      tomotherapy delivery to facilitate this aim.

PMID- 15446798
TI  - Response corrections for solid-state detectors in megavoltage photon dosimetry.
AB  - Solid-state detectors offer high sensitivity, stability and resolution and are
      frequently the dosimeter of choice for on-line dosimetry and small field
      therapies such as stereotactic radiosurgery. The departure from tissue
      equivalence of many solid-state devices, including diodes and MOSFETs, has to be
      carefully considered at lower energies and for Compton scattered radiation where
      the strongly Z-dependent photoelectric effect is significant. A modification of
      Burlin cavity theory is proposed that treats primary and scatter photon spectra
      separately and this has been applied to determine the correction factors for
      diode detector measurements of 6 and 15 MV linear accelerator beams. Uncorrected,
      an unshielded diode overestimates the dose at depth by as much as 15% for the 6
      MV beam. The model predicts the effect to within 1% for both energies offering a
      basis for the correction of diodes for use in routine dosimetry.

PMID- 15446799
TI  - Targeted alpha therapy for cancer.
AB  - Targeted alpha therapy (TAT) offers the potential to inhibit the growth of
      micrometastases by selectively killing isolated and preangiogenic clusters of
      cancer cells. The practicality and efficacy of TAT is tested by in vitro and in
      vivo studies in melanoma, leukaemia, colorectal, breast and prostate cancers, and
      by a phase 1 trial of intralesional TAT for melanoma. The alpha-emitting
      radioisotope used is Bi-213, which is eluted from the Ac-225 generator and
      chelated to a cancer specific monoclonal antibody (mab) or protein (e.g.
      plasminogen activator inhibitor-2 PAI2) to form the alpha-conjugate (AC). Stable
      alpha-ACs have been produced which have been tested for specificity and
      cytotoxicity in vitro against melanoma (9.2.27 mab), leukaemia (WM60), colorectal
      (C30.6), breast (PAI2, herceptin), ovarian (PAI2, herceptin, C595), prostate
      (PAI2, J591) and pancreatic (PAI2, C595) cancers. Subcutaneous inoculation of 1
      1.5 million human cancer cells into the flanks of nude mice causes tumours to
      grow in all mice. Tumour growth is compared for untreated controls, nonspecific
      AC and specific AC, for local (subcutaneous) and systemic (tail vein or
      intraperitoneal) injection models. The 213Bi-9.2.27 AC is injected into secondary
      skin melanomas in stage 4 patients in a dose escalation study to determine the
      effective tolerance dose, and to measure kinematics to obtain the equivalent dose
      to organs. In vitro studies show that TAT is one to two orders of magnitude more
      cytotoxic to targeted cells than non-specific ACs, specific beta emitting
      conjugates or free isotopes. In vivo local TAT at 2 days post-inoculation
      completely prevents tumour formation for all cancers tested so far. Intra
      lesional TAT can completely regress advanced sc melanoma but is less successful
      for breast and prostate cancers. Systemic TAT inhibits the growth of sc melanoma
      xenografts and gives almost complete control of breast and prostate cancer tumour
      growth. Intralesional doses up to 450 microCi in human patients are effective in
      regressing melanomas, with no concomitant complications. These results point to
      the application of local and systemic TAT in the management of secondary cancer.
      Results of the phase 1 clinical trial of TAT of subcutaneous, secondary melanoma
      indicate proof of the principle that TAT can make tumours in patients regress.

PMID- 15446800
TI  - Two-dimensional and quasi-three-dimensional dosimetry of hadron and photon beams
      with the Magic Cube and the Pixel Ionization Chamber.
AB  - Two detectors for fast two-dimensional (2D) and quasi-three-dimensional (quasi
      3D) verification of the dose delivered by radiotherapy beams have been developed
      at University and Istituto Nazionale di Fisica Nucleare (INFN) of Torino. The
      Magic Cube is a stack of strip-segmented ionization chambers interleaved with
      water-equivalent slabs. The parallel plate ionization chambers have a sensitive
      area of 24 x 24 cm2, and consist of 0.375 cm wide and 24 cm long strips. There
      are a total of 64 strips per chamber. The Magic Cube has been tested with the
      clinical proton beam at Loma Linda University Medical Centre (LLUMC), and was
      shown to be capable of fast and precise quasi-3D dose verification. The Pixel
      Ionization Chamber (PXC) is a detector with pixel anode segmentation. It is a 32
      x 32 matrix of 1024 cylindrical ionization cells arranged in a square 24 x 24 cm2
      area. Each cell has 0.4 cm diameter and 0.55 cm height, at a pitch of 0.75 cm
      separates the centre of adjacent cells. The sensitive volume of each single
      ionization cell is 0.07 cm3. The detectors are read out using custom designed
      front-end microelectronics and a personal computer-based data acquisition system.
      The PXC has been used to verify dynamic intensity-modulated radiotherapy for head
      and-neck and breast cancers.

PMID- 15446801
TI  - A state-of-the-art epithermal neutron irradiation facility for neutron capture
      therapy.
AB  - At the Massachusetts Institute of Technology (MIT) the first fission converter
      based epithermal neutron beam (FCB) has proven suitable for use in clinical
      trials of boron neutron capture therapy (BNCT). The modern facility provides a
      high intensity beam together with low levels of contamination that is ideally
      suited for use with future, more selective boron delivery agents. Prescriptions
      for normal tissue tolerance doses consist of 2 or 3 fields lasting less than 10
      min each with the currently available beam intensity, that are administered with
      an automated beam monitoring and control system to help ensure safety of the
      patient and staff alike. A quality assurance program ensures proper functioning
      of all instrumentation and safety interlocks as well as constancy of beam output
      relative to routine calibrations. Beam line shutters and the medical room walls
      provide sufficient shielding to enable access and use of the facility without
      affecting other experiments or normal operation of the multipurpose research
      reactor at MIT. Medical expertise and a large population in the greater Boston
      area are situated conveniently close to the university, which operates the
      research reactor 24 h a day for approximately 300 days per year. The operational
      characteristics of the facility closely match those established for conventional
      radiotherapy, which together with a near optimum beam performance ensure that the
      FCB is capable of determining whether the radiobiological promise of NCT can be
      realized in routine practice.

PMID- 15446802
TI  - A small-body portable graphite calorimeter for dosimetry in low-energy clinical
      proton beams.
AB  - Calorimetry has been recommended and performed in proton beams for some time, but
      never has graphite calorimetry been used as a reference dosimeter in clinical
      proton beams. Furthermore, only a few calorimetry measurements have been reported
      in ocular proton beams. In this paper we describe the construction and
      performance of a small-body portable graphite calorimeter for clinical low-energy
      proton beams. Perturbation correction factors for the gap effect, volume
      averaging effect, heat transfer phenomena and impurity effect are calculated and
      applied in a comparison with ionization chamber dosimetry following IAEA TRS-398.
      The ratio of absorbed dose to water obtained from the calorimeter measurements
      and from the ionization measurements varied between 0.983 and 1.019, depending on
      the beam type and the ionization chamber calibration modality. Standard
      uncertainties on these values varied between 1.9% and 2.5% including a
      substantial contribution from the kQ values in IAEA TRS-398. The (Wair/e)p values
      inferred from these measurements varied between 33.6 J C(-1) and 34.9 J C(-1)
      with similar standard uncertainties. A number of improvements for the small-body
      portable graphite calorimeter and the experimental set-up are suggested for
      potential reduction of the uncertainties.

PMID- 15446803
TI  - Applicability of CORVUS pencil beam model and scatter dose model for intensity
      modulated neutron therapy.
AB  - Intensity modulated neutron radiotherapy (IMNRT) is currently being investigated
      as a mechanism to improve dose conformality in neutron radiotherapy, thereby
      minimizing normal tissue toxicity. This study investigates the applicability of
      two different dose calculation algorithms for IMNRT, a commercial system which
      utilizes a finite size pencil beam (FSPB) model, and an in-house planning system
      which uses a differential scatter air ratio (DSAR) method. Calculated dose
      distributions were compared with measured profiles for validation purposes. The
      beam-profiles matched to within +/-3% in the central region of the field. The 80
      20% penumbra width as measured using an ionization chamber varied as 0.6 cm and
      1.0 cm for 3 x 3 and 10 x 10 cm2 profile at a depth of 2.5 cm. The FSPB model
      fitted the data to a penumbra width of 0.1 cm for both 3 x 3 and 10 x 10 cm2
      profiles. These results indicate that the commercial system needs further
      investigation. However, the in-house planning system has been validated for small
      irregular fields for IMNRT to an accuracy of +/-5%. Absolute dose measurements
      agreed with the calculated doses to within +/-3%.

PMID- 15446804
TI  - Modelling of post-irradiation accelerated repopulation in squamous cell
      carcinomas.
AB  - The mechanisms postulated to be responsible for the accelerated repopulation of
      squamous cell carcinomas during radiotherapy are the loss of asymmetry of stem
      cell division, acceleration of stem cell division, abortive division and/or
      recruitment of the non-cycling cell with proliferative capacity. Although
      accelerated repopulation was observed with recruitment and accelerated cell
      cycles, it was not sufficient to cause an observable change to the survival
      curve. However, modelling the loss of asymmetry in stem cell division has
      reshaped the curve with a 'growth' shoulder. Cell recruitment was not found to be
      a major contributor to accelerated tumour repopulation. A more significant
      contribution was provided through the multiplication of surviving tumour stem
      cells during radiotherapy, by reducing their cell cycle time, and due to loss of
      asymmetry of stem cell division.

PMID- 15446805
TI  - Theoretical analysis of microdosimetric spectra and cluster formation for 103Pd
      and 125I photon emitters.
AB  - In this work we have compared 125I or 103Pd from a microdosimetric point of view.
      The photon spectra at different positions around the seeds have first been
      calculated using EGSnrc Monte Carlo (MC) code. These photon spectra are used as
      input for the event-by-event MC code TRION to calculate the microdosimetric
      lineal energy (y) distribution for each isotope. The microdosimetric dose average
      lineal energy, yD, calculated in a sphere of 1 microm is 3.5 keV microm(-1) for
      125I and 4.0 keV microm(-1) for 103Pd, agreeing well with values reported in the
      literature. yD in a 1 microm sphere diminishes slightly with the distance from
      the seed for 103Pd. This is due to the spectral hardening caused by the presence
      of a gamma-ray of 357.5 keV in the initial spectrum of 103Pd. In parallel with
      the calculation of the microdosimetric spectra, we have analysed the distribution
      of the size of the energy deposition clusters generated by these low energy
      photons in structures of 2 and 10 nm of radius. Due to Compton interactions, the
      fraction of very low energy electrons (<5 keV) generated by 125I photons is 51%,
      whereas it is only 27% for 103Pd. As these electrons deposit their energy very
      locally, the pattern of energy depositions contains more clusters of a few nm of
      radius for 125I than for 103Pd; the mean cluster orders are respectively 3.3 and
      3.0 for 10 nm clusters. This is in opposition with the prediction based on the
      microdosimetric spectrum and the parameter yD and could be of importance for the
      damage to the cells.

PMID- 15446806
TI  - Statistical methods for clinical verification of dose-response parameters related
      to esophageal stricture and AVM obliteration from radiotherapy.
AB  - The purpose of this work is to provide some statistical methods for evaluating
      the predictive strength of radiobiological models and the validity of dose
      response parameters for tumour control and normal tissue complications. This is
      accomplished by associating the expected complication rates, which are calculated
      using different models, with the clinical follow-up records. These methods are
      applied to 77 patients who received radiation treatment for head and neck cancer
      and 85 patients who were treated for arteriovenous malformation (AVM). The three
      dimensional dose distribution delivered to esophagus and AVM nidus and the
      clinical follow-up results were available for each patient. Dose-response
      parameters derived by a maximum likelihood fitting were used as a reference to
      evaluate their compatibility with the examined treatment methodologies. The
      impact of the parameter uncertainties on the dose-response curves is
      demonstrated. The clinical utilization of the radiobiological parameters is
      illustrated. The radiobiological models (relative seriality and linear Poisson)
      and the reference parameters are validated to prove their suitability in
      reproducing the treatment outcome pattern of the patient material studied
      (through the probability of finding a worse fit, area under the ROC curve and
      chi2 test). The analysis was carried out for the upper 5 cm of the esophagus
      (proximal esophagus) where all the strictures are formed, and the total volume of
      AVM. The estimated confidence intervals of the dose-response curves appear to
      have a significant supporting role on their clinical implementation and use.

PMID- 15446808
TI  - Cut-and-unfold approach to fullerene enumeration.
AB  - A simple and effective approach for the enumeration of fullerene structures is
      proposed. The method combines the formalism of a fullerene graph cut-and-unfold
      onto a planar triangular lattice and a topological description of closed quasi-2D
      clusters. A tabulation of possible fullerene graphs Cn is given for the number of
      atoms 20 < or = n < or = 150.

PMID- 15446807
TI  - In vivo mammary tumourigenesis in the Sprague-Dawley rat and microdosimetric
      correlates.
AB  - Standard methods for risk assessments resulting from human exposures to mixed
      radiation fields in Space consisting of different particle types and energies
      rely upon quality factors. These are generally defined as a function of linear
      energy transfer (LET) and are assumed to be proportional to the risk. In this
      approach, it is further assumed that the risks for single exposures from each of
      the radiation types add linearly. Although risks of cancer from acute exposures
      to photon radiations have been measured in humans, quality factors for protons
      and ions of heavier atomic mass are generally inferred from animal and/or
      cellular data. Because only a small amount of data exists for such particles,
      this group has been examining tumourigenesis initiated by energetic protons and
      iron ions. In this study, 741 female Sprague-Dawley rats were irradiated or sham
      irradiated at approximately 60 days of age with 250 MeV protons, 1 GeV/nucleon
      iron ions or both protons and iron ions. The results suggest that the risk of
      mammary tumours in the rats sequentially irradiated with 1 GeV/nucleon 56Fe ions
      and 250 MeV protons is less than additive. These data in conjunction with earlier
      results further suggest that risk assessments in terms of only mean LETs of the
      primary cosmic rays may be insufficient to accurately evaluate the relative risks
      of each type of particle in a radiation field of mixed radiation qualities.

PMID- 15446809
TI  - Random walks and chemical graph theory.
AB  - Simple random walks probabilistically grown step by step on a graph are
      distinguished from walk enumerations and associated equipoise random walks.
      Substructure characteristics and graph invariants correspondingly defined for the
      two types of random walks are then also distinct, though there often are
      analogous relations. It is noted that the connectivity index as well as some
      resistance-distance-related invariants make natural appearances among the
      invariants defined from the simple random walks.

PMID- 15446810
TI  - 4D-fingerprints, universal QSAR and QSPR descriptors.
AB  - An elusive goal in the field of chemoinformatics and molecular modeling has been
      the generation of a set of descriptors that, once calculated for a molecule, may
      be used in a wide variety of applications. Since such universal descriptors are
      generated free from external constraints, they are inherently independent of the
      data set in which they are employed. The realization of a set of universal
      descriptors would significantly streamline such chemoinformatics tasks as virtual
      high-throughout screening (VHTS) and toxicity profiling. The current study
      reports the derivation and validation of a potential set of universal
      descriptors, referred to as the 4D-fingerprints. The 4D-fingerprints are derived
      from the 4D-molecular similarity analysis. To evaluate the applicability of the
      4D-fingerprints as universal descriptors, they are used to generate descriptive
      QSAR models for 5 independent training sets. Each of the training sets has been
      analyzed previously by several varying QSAR methods, and the results of the
      models generated using the 4D-fingerprints are compared to the results of the
      previous QSAR analyses. It was found that the models generated using the 4D
      fingerprints are comparable in quality, based on statistical measures of fit and
      test set prediction, to the previously reported models for the other QSAR
      methods. This finding is particularly significant considering the 4D-fingerprints
      are generated independent of external constraints such as alignment, while the
      QSAR methods used for comparison all require an alignment analysis.

PMID- 15446811
TI  - Prediction of homology model quality with multivariate regression.
AB  - A new method has been developed for prediction of homology model quality directly
      from the sequence alignment, using multivariate regression. Hence, the expected
      quality of future homology models can be estimated using only information about
      the primary structure. This method has been applied to protein kinases and can
      easily be extended to other protein families. Homology model quality for a
      reference set of homology models was verified by comparison to experimental
      structures, by calculation of root-mean-square deviations (RMSDs) and comparison
      of interresidue contact areas. The homology model quality measures were then used
      as dependent variables in a Partial Least Squares (PLS) regression, using a
      matrix of alignment score profiles found from the Point Accepted Mutation (PAM)
      250 similarity matrix as independent variables. This resulted in a regression
      model that can be used to predict the accuracy of future homology models from the
      sequence alignment. Using this method, one can identify the target-template
      combinations that are most likely to give homology models of sufficient quality.
      Hence, this method can be used to effectively choose the optimal templates to use
      for the homology modeling. The method's ability to guide the choice of homology
      modeling templates was verified by comparison of success rates to those obtained
      using BLAST scores and target-template sequence identities, respectively. The
      results indicate that the method presented here performs best in choosing the
      optimal homology modeling templates. Using this method, the optimal template was
      chosen in 86% of the cases, as compared to 62% using BLAST scores, and 57% using
      sequence identities. The method presented here can also be used to identify
      regions of the protein structure that are difficult to model, as well as
      alignment errors. Hence, this method is a useful tool for ensuring that the best
      possible homology model is generated.

PMID- 15446812
TI  - Oriented 2-cell embeddings of a graph and their symmetry classification:
      generating algorithms and case study of the mobius-kantor graph.
AB  - We discuss a method to derive all symmetry-distinct oriented 2-cell embeddings of
      a given graph and classify them based on their symmetry. As an example, we apply
      the algorithm to the highly symmetrical trivalent Mobius-Kantor graph.
      Considering the derived 2-cell embeddings as carbon networks leads to some
      interesting negative curvature carbon allotropes.

PMID- 15446813
TI  - Resonance energy in graphite.
AB  - According to Zhu et al. the resonance energy/electron (REPE) in infinite graphite
      sheets is equal to 0.17 eV. In the present work the REPE was calculated for
      parallelogram-shaped graphite sheets (PSGSs). The number of Kekule structures and
      contributions of benzene-like and naphthalene-like conjugated circuits were taken
      into account. Analogously to polyacenes, it was found that REPE = 0.00 eV in
      PSGSs. The convergence is slow. These results indicate that PSGS is less
      "aromatic" than its infinite counterpart. Therefore addition reactions are
      expected to be less difficult to carry out in PSGSs than in infinite or
      rectangular graphite sheets.

PMID- 15446814
TI  - Some basic data structures and algorithms for chemical generic programming.
AB  - Here, we report a template library used for molecular operation, the Molecular
      Handling Template Library (MHTL). The library includes some generic data
      structures and generic algorithms, and the two parts are associated with each
      other by two concepts: Properties and Molecule. The concept Properties describes
      the interface to access objects' properties, and the concept Molecule describes
      the minimum requirement for a molecular class. Data structures include seven
      models of Properties, each using a different method to access properties, and two
      models of molecular classes. Algorithms include molecular file manipulation
      subroutines, SMARTS language interpreter and matcher functions, and molecular
      OpenGL rendering functions.

PMID- 15446815
TI  - Heuristic extraction of rules in pruned artificial neural networks models used
      for quantifying highly overlapping chromatographic peaks.
AB  - The suitability of an approach for extracting heuristic rules from trained
      artificial neural networks (ANNs) pruned by a regularization method and with
      architectures designed by evolutionary computation for quantifying highly
      overlapping chromatographic peaks is demonstrated. The ANN input data are
      estimated by the Levenberg-Marquardt method in the form of a four-parameter
      Weibull curve associated with the profile of the chromatographic band. To test
      this approach, two N-methylcarbamate pesticides, carbofuran and propoxur, were
      quantified using a classic peroxyoxalate chemiluminescence reaction as a
      detection system for chromatographic analysis. Straightforward network topologies
      (one and two outputs models) allow the analytes to be quantified in concentration
      ratios ranging from 1:7 to 5:1 with an average standard error of prediction for
      the generalization test of 2.7 and 2.3% for carbofuran and propoxur,
      respectively. The reduced dimensions of the selected ANN architectures,
      especially those obtained after using heuristic rules, allowed simple
      quantification equations to be developed that transform the input variables into
      output variables. These equations can be easily interpreted from a chemical point
      of view to attain quantitative analytical information regarding the effect of
      both analytes on the characteristics of chromatographic bands, namely profile,
      dispersion, peak height, and residence time.

PMID- 15446816
TI  - ADME evaluation in drug discovery. 5. Correlation of Caco-2 permeation with
      simple molecular properties.
AB  - The correlations between Caco-2 permeability (logPapp) and molecular properties
      have been investigated. A training set of 77 structurally diverse organic
      molecules was used to construct significant QSAR models for Caco-2 cell
      permeation. Cellular permeation was found to depend primarily upon experimental
      distribution coefficient (logD) at pH = 7.4, high charged polar surface area
      (HCPSA), and radius of gyration (rgyr). Among these three descriptors, logD may
      have the largest impact on diffusion through Caco-2 cell because logD shows
      obvious linear correlation with logPapp (r=0.703) when logD is smaller than 2.0.
      High polar surface area will be unfavorable to achieve good Caco-2 permeability
      because higher polar surface area will introduce stronger H-bonding interactions
      between Caco-2 cells and drugs. The comparison among HCPSA, PSA (polar surface
      area), and TPSA (topological polar surface area) implies that high-charged atoms
      may be more important to the interactions between Caco-2 cell and drugs. Besides
      logD and HCPSA, rgyr is also closely connected with Caco-2 permeabilities. The
      molecules with larger rgyr are more difficult to cross Caco-2 monolayers than
      those with smaller rgyr. The descriptors included in the prediction models permit
      the interpretation in structural terms of the passive permeability process,
      evidencing the main role of lipholiphicity, H-bonding, and bulk properties.
      Besides these three molecular descriptors, the influence of other molecular
      descriptors was also investigated. From the calculated results, it can be found
      that introducing descriptors concerned with molecular flexibility can improve the
      linear correlation. The resulting model with four descriptors bears good
      statistical significance, n = 77, r = 0.82, q = 0.79, s = 0.45, F = 35.7. The
      actual predictive abilities of the QSAR model were validated through an external
      validation test set of 23 diverse compounds. The predictions for the tested
      compounds are as the same accuracy as the compounds of the training set and
      significantly better than those predicted by using the model reported. The good
      predictive ability suggests that the proposed model may be a good tool for fast
      screening of logPapp for compound libraries or large sets of new chemical
      entities via combinatorial chemistry synthesis.

PMID- 15446817
TI  - Information content in organic molecules: quantification and statistical
      structure via Brownian processing.
AB  - Information and organic molecules were the subject of two previous works from
      this lab (Graham and Schacht, J. Chem. Inf. Comput. Sci. 2000, 40, 187; Graham,
      J. Chem. Inf. Computer Sci. 2002, 42, 215). We delve further in this paper by
      examining organic structure graphs as objects of Brownian information processing.
      In so doing, tools are introduced which quantify and correlate molecular
      information to several orders. When the results are combined with energy data, an
      enhanced informatic view of covalent bond networks is obtained. The information
      properties of select molecules and libraries are illustrated. Notably, Brownian
      processing accommodates all possible compounds and libraries, not just ones
      registered in chemical databases. This approach establishes important features of
      the statistical structure underlying carbon chemistry.

PMID- 15446818
TI  - Information content in organic molecules: reaction pathway analysis via Brownian
      processing.
AB  - Carbon chemistry offers infinite possibilities for molecules as information
      carriers. Moreover, there is no boundary on the number of ways in which a
      carrier's information can change via a chemical reaction. Organic reaction
      pathways thus pose new types of informatic variables which compel
      characterization using Brownian methods. We apply the tools of the preceding
      paper to these variable types for select reactions and classes. Along the way,
      geometric descriptors are formulated which complement the structure graph
      sequences of chemistry texts and journals. In addition, the statistical structure
      underpinning carbon transformations is explored more deeply. Overall, this work
      brings to light several informatic principles of organic reactions. Knowledge of
      these can assist in synthetic designs on both large- and small-scales. Brownian
      methods are able to address the pathway structures of all organic reactions:
      those reported in the literature, explored in the lab, or in the developmental
      stage.

PMID- 15446819
TI  - Assessment of the oral rat chronic lowest observed adverse effect level model in
      TOPKAT, a QSAR software package for toxicity prediction.
AB  - The performance of the rat chronic lowest observed adverse effect level (LOAEL,
      the lowest exposure level at which there are biologically significant increases
      in the severity of adverse effects) model in Toxicity Prediction by Komputer
      Assisted Technology (TOPKAT), a commercial quantitative structure-activity
      relationship software package, was tested on a database of chemicals that are of
      interest to the U.S. EPA's Office of Pesticide Programs. The testing was repeated
      on a database of chemicals from three U.S. EPA sources that report peer-reviewed
      LOAELs. The results of this study were also contrasted with the results of the
      testing performed during TOPKAT's model-building process.

PMID- 15446820
TI  - Effect of molecular descriptor feature selection in support vector machine
      classification of pharmacokinetic and toxicological properties of chemical
      agents.
AB  - Statistical-learning methods have been developed for facilitating the prediction
      of pharmacokinetic and toxicological properties of chemical agents. These methods
      employ a variety of molecular descriptors to characterize structural and
      physicochemical properties of molecules. Some of these descriptors are
      specifically designed for the study of a particular type of properties or agents,
      and their use for other properties or agents might generate noise and affect the
      prediction accuracy of a statistical learning system. This work examines to what
      extent the reduction of this noise can improve the prediction accuracy of a
      statistical learning system. A feature selection method, recursive feature
      elimination (RFE), is used to automatically select molecular descriptors for
      support vector machines (SVM) prediction of P-glycoprotein substrates (P-gp),
      human intestinal absorption of molecules (HIA), and agents that cause torsades de
      pointes (TdP), a rare but serious side effect. RFE significantly reduces the
      number of descriptors for each of these properties thereby increasing the
      computational speed for their classification. The SVM prediction accuracies of P
      gp and HIA are substantially increased and that of TdP remains unchanged by RFE.
      These prediction accuracies are comparable to those of earlier studies derived
      from a selective set of descriptors. Our study suggests that molecular feature
      selection is useful for improving the speed and, in some cases, the accuracy of
      statistical learning methods for the prediction of pharmacokinetic and
      toxicological properties of chemical agents.

PMID- 15446821
TI  - CoNTub: an algorithm for connecting two arbitrary carbon nanotubes.
AB  - We have developed the first computer program for determining the coordinates of
      heterojunctions between two arbitrary carbon nanotubes. This software implements
      the topological algebra based on the concept of strip, a continuous subset of
      carbon rings containing all the topological defects (nonhexagonal carbon rings).
      The user easily generates any heterojunction by merely introducing the indices
      (i,j) and length of the two nanotubes to be connected. The resulting structure is
      immediately visualized and can be exported in the protein-data-bank (PDB) format.
      Two classes of heterojunctions are distinguished depending on whether a cone
      between the connected nanotubes is required. This method is applicable to all
      kinds of two nanotube heterojunctions, including Dunlap's knees and others
      related. In addition, this program also generates single- and multiwalled carbon
      nanotubes (SWNT and MWNT). This application has been implemented as a Java
      applet, and it is freely available at the following web address:
      http://www.ugr.es/local/gmdm/java/contub/contub.html

PMID- 15446822
TI  - Nonlinear prediction of quantitative structure-activity relationships.
AB  - Predicting the log of the partition coefficient P is a long-standing benchmark
      problem in Quantitative Structure-Activity Relationships (QSAR). In this paper we
      show that a relatively simple molecular representation (using 14 variables) can
      be combined with leading edge machine learning algorithms to predict logP on new
      compounds more accurately than existing benchmark algorithms which use complex
      molecular representations.

PMID- 15446823
TI  - Manual construction and mathematics- and computer-aided counting of
      stereoisomers. The example of oligoinositols.
AB  - Two methods to obtain numbers of stereoisomers and of achiral stereoisomers of a
      given molecular structure are detailed on the example of di- and triinositols.
      The first method is manual exhaustive construction free of redundance of all
      stereoisomers, which is rendered feasible by symmetry considerations despite the
      large number of isomeric triinositols (82176). The second method is counting
      without constructing, made possible by use of a mathematical tool, the Cauchy
      Frobenius lemma, which actually is a formalized manner of considering symmetry.
      The results are compared to those obtained by computer-aided stereoisomer
      generation using the program MOLGEN 3.5. It is demonstrated that in their results
      all three methods agree.

PMID- 15446824
TI  - Analysis of similarity/dissimilarity of DNA sequences based on nonoverlapping
      triplets of nucleotide bases.
AB  - We consider a 6-D representation of triplets of nucleotide bases of DNA
      sequences. Based on this representation, we outline an approach by constructing a
      3-component vector whose components are the normalized leading eigenvalues of the
      L/L matrices associated with the triplets derived from DNA sequences. The
      examination of similarities/dissimilarities among the coding sequences of the
      first exon of beta-globin gene of different species illustrates the utility of
      the approach.

PMID- 15446825
TI  - Evaluation and prediction of stereoisomerizations in comprehensive two
      dimensional chromatography.
AB  - Conformational and configurational changes such as isomerizations,
      epimerizations, diastereomerizations and, enantiomerizations are important for
      the investigation of a large variety of processes ranging from protein folding to
      the stereostability of drugs. Under optimized conditions, these processes lead to
      an elution profile characterized by a plateau formation between the two
      interconverting species in chromatographic separations in a certain temperature
      range. By temperature-dependent measurements and subsequent computer simulation
      of the experimental chromatograms, the forward and backward rate constants k1 and
      k(-1), the Gibb's energy DeltaG++, activation enthalpy DeltaH++, and entropy
      DeltaS++ can be obtained. Due to its high efficiency two-dimensional
      chromatography is able to resolve the time-dependent distribution of the two
      species in the second dimension, thereby yielding the precise ratio of
      stereoisomers. An algorithm for the simulation and evaluation of two-dimensional
      chromatographic experiments has been developed, based on the theoretical plate
      model, which allows the determination of rate constants and barriers of
      isomerization, epimerization, and enantiomerization processes from two
      dimensional chromatographic experiments. In the present article a detailed
      description of the extended theoretical plate model required for the simulation,
      the methods available, and examples for the evaluation of complex experimental
      data and the prediction of the separation conditions to observe isomerization,
      epimerizations, and enantiomerizations in two-dimensional chromatography are
      given.

PMID- 15446826
TI  - A graphical tool for the prediction of vicinal proton-proton 3J(HH) coupling
      constants.
AB  - The easy to use and free available graphical tool MestRe-J, developed for Win-32
      platforms, calculates the vicinal proton-proton coupling constants 3J(HH) from
      the torsion angle phi between the coupled protons for the two kinds of
      generalized Karplus equations developed by Altona's group as well as for
      equations from other authors. Besides the classical Haasnoot-de Leeuw-Altona
      equations, including individual substituent effects that depend on their relative
      Huggins's electronegativities Deltachi, the program incorporates the more recent
      and precise Diez-Altona-Donders equations. The substituent effects in these
      equations, that include effects of interactions between substituents, depend on
      substituent parameters lambda optimized from the 3J(HH) couplings to methyl
      groups. Weighted time-averaged couplings can be calculated. The equations for
      3J(HH) can be solved to provide the torsion angles phi.

PMID- 15446827
TI  - Evaluation of mutual information and genetic programming for feature selection in
      QSAR.
AB  - Feature selection is a key step in Quantitative Structure Activity Relationship
      (QSAR) analysis. Chance correlations and multicollinearity are two major problems
      often encountered when attempting to find generalized QSAR models for use in drug
      design. Optimal QSAR models require an objective variable relevance analysis step
      for producing robust classifiers with low complexity and good predictive
      accuracy. Genetic algorithms coupled with information theoretic approaches such
      as mutual information have been used to find near-optimal solutions to such
      multicriteria optimization problems. In this paper, we describe a novel approach
      for analyzing QSAR data based on these methods. Our experiments with the Thrombin
      dataset, previously studied as part of the KDD (Knowledge Discovery and Data
      Mining) Cup 2001 demonstrate the feasibility of this approach. It has been found
      that it is important to take into account the data distribution, the rule
      "interestingness", and the need to look at more invariant and monotonic measures
      of feature selection.

PMID- 15446828
TI  - QSAR models for the prediction of binding affinities to human serum albumin using
      the heuristic method and a support vector machine.
AB  - The binding affinities to human serum albumin for 94 diverse drugs and drug-like
      compounds were modeled with the descriptors calculated from the molecular
      structure alone using a quantitative structure-activity relationship (QSAR)
      technique. The heuristic method (HM) and support vector machine (SVM) were
      utilized to construct the linear and nonlinear prediction models, leading to a
      good correlation coefficient (R2) of 0.86 and 0.94 and root-mean-square errors
      (rms) of 0.212 and 0.134 albumin drug binding affinity units, respectively.
      Furthermore, the models were evaluated by a 10 compound external test set,
      yielding R2 of 0.71 and 0.89 and rms error of 0.430 and 0.222. The specific
      information described by the heuristic linear model could give some insights into
      the factors that are likely to govern the binding affinity of the compounds and
      be used as an aid to the drug design process; however, the prediction results of
      the nonlinear SVM model seem to be better than that of the HM.

PMID- 15446829
TI  - Partitioning of pi-electrons in rings of polycyclic conjugated hydrocarbons. 5.
      Nonalternant compounds.
AB  - All possible nonalternant hydrocarbons with a total of two, three, or four 5-, 6
      , and 7-membered rings have been examined for the partition of their pi-electrons
      by averaging over all Kekule structures (considered to contribute equally to the
      electron distribution) the pi-electrons in each ring in accordance to the rules
      introduced earlier: for each double bond shared with another ring one pi-electron
      is taken into account, and for double bonds that are not shared two pi-electrons
      are added. The trends observed for the partitions are discussed, and a
      comprehensive bibliography is provided as Supporting Information for all such
      systems, including both experimental and theoretical published data.

PMID- 15446830
TI  - Similarity searching of chemical databases using atom environment descriptors
      (MOLPRINT 2D): evaluation of performance.
AB  - A molecular similarity searching technique based on atom environments,
      information-gain-based feature selection, and the naive Bayesian classifier has
      been applied to a series of diverse datasets and its performance compared to
      those of alternative searching methods. Atom environments are count vectors of
      heavy atoms present at a topological distance from each heavy atom of a molecular
      structure. In this application, using a recently published dataset of more than
      100000 molecules from the MDL Drug Data Report database, the atom environment
      approach appears to outperform fusion of ranking scores as well as binary kernel
      discrimination, which are both used in combination with Unity fingerprints.
      Overall retrieval rates among the top 5% of the sorted library are nearly 10%
      better (more than 14% better in relative numbers) than those of the second best
      method, Unity fingerprints and binary kernel discrimination. In 10 out of 11 sets
      of active compounds the combination of atom environments and the naive Bayesian
      classifier appears to be the superior method, while in the remaining dataset,
      data fusion and binary kernel discrimination in combination with Unity
      fingerprints is the method of choice. Binary kernel discrimination in combination
      with Unity fingerprints generally comes second in performance overall. The
      difference in performance can largely be attributed to the different molecular
      descriptors used. Atom environments outperform Unity fingerprints by a large
      margin if the combination of these descriptors with the Tanimoto coefficient is
      compared. The naive Bayesian classifier in combination with information-gain
      based feature selection and selection of a sensible number of features performs
      about as well as binary kernel discrimination in experiments where these
      classification methods are compared. When used on a monoaminooxidase dataset,
      atom environments and the naive Bayesian classifier perform as well as binary
      kernel discrimination in the case of a 50/50 split of training and test
      compounds. In the case of sparse training data, binary kernel discrimination is
      found to be superior on this particular dataset. On a third dataset, the atom
      environment descriptor shows higher retrieval rates than other 2D fingerprints
      tested here when used in combination with the Tanimoto similarity coefficient.
      Feature selection is shown to be a crucial step in determining the performance of
      the algorithm. The representation of molecules by atom environments is found to
      be more effective than Unity fingerprints for the type of biological receptor
      similarity calculations examined here. Combining information prior to scoring and
      including information about inactive compounds, as in the Bayesian classifier and
      binary kernel discrimination, is found to be superior to posterior data fusion
      (in the datasets tested here).

PMID- 15446831
TI  - Group-theoretical discussion on the E/Z-nomenclature for ethylene derivatives.
      Discrimination between RS-stereoisomeric groups and stereoisomeric groups.
AB  - The hierarchy of point groups, RS-stereoisomeric groups, stereoisomeric groups,
      and isoskeletal groups is discussed to comprehend the chirality, RS
      stereogenicity, stereogenicity, and isoskeletal isomerism for ethylene
      derivatives. The RS-stereoisomeric groups for ethylene derivatives have been
      clarified not to coincide with their stereoisomeric groups, so that diastereomers
      (E/Z-isomers) are not identical with RS-diastereomers. To discuss the
      relationship among RS-diastereomers, m-diastereomers, and isoskeletal isomers, we
      have proposed the concepts of extended stereoisograms and extended stereoisogram
      sets, where the term "m-diastereomers" is coined to show its difference from the
      traditional term "diastereomer". Thereby, ethylene derivatives are classified
      into Types II-II/II-II/II-II, IV-IV/IV-IV/IV-IV, etc. on the basis of relevant
      stereoisograms (Types I to V). The stereoisomerism of ethylenes has been
      concluded to be treated in terms of m-diastereomers characterized by the E/Z
      nomenclature but not to be treated in terms of RS-diastereomers characterized by
      the RS-nomenclaure.

PMID- 15446832
TI  - Determination of lithium cation basicity from molecular structure.
AB  - A quantitative structure-property relationship (QSPR) is developed to calculate
      the Lithium Cationic Basicity (LCB) of a large set of 229 compounds, of very
      different chemical nature. The proposed models derived from multiple linear
      regression analysis (MLRA) and computational neural networks (CNN) contain seven
      descriptors calculated solely from the molecular structure of compounds. The
      models were validated by an external prediction set. Good results were obtained
      from both methodologies, being the best those from CNN, that give a rms error of
      6.54 (R2 = 0.954) and an average error of 3.57% for the training set; for the
      prediction set the rms error is 8.61 (R2 = 0.914) and the average error 4.39%.
      The models derived from the two approaches contain descriptors that belong to the
      same classes, constitutional and electrostatic. The comparison with the results
      obtained from high level theoretical methods shows that the values obtained from
      the QSPR approach are very similar and even better, especially when the sets
      compared are large and contain compounds of different chemical structure. These
      good results shows that, despite the complexity of Li+-base interactions, the
      proposed models contain descriptors which encode properly the characteristics of
      the molecules directly related to their gas-phase basicity against the Li
      cations.

PMID- 15446833
TI  - Structure elucidation from 2D NMR spectra using the StrucEluc expert system:
      detection and removal of contradictions in the data.
AB  - The elucidation of chemical structures from 2D NMR data commonly utilizes a
      combination of COSY, HMQC/HSQC, and HMBC data. Generally COSY connectivities are
      assumed to mostly describe the separation of protons that are separated by 1
      skeletal bond (3JHH), while HMBC connectivities represent protons separated from
      carbon atoms by 1 to 2 skeletal bonds (2JCH and 3JCH). Obviously COSY and HMBC
      connectivities of lengths greater than those described have been detected. Though
      experimental techniques have recently been described to aid in the identification
      of the nature of the couplings the detection of whether a coupling is 2-bond or
      greater still remains a challenge in most laboratories. In the StrucEluc software
      system the common lengths of the connectivities, 1-bond for COSY and 1- or 2-bond
      for HMBC, derived from 2D NMR data are set as the default. Therefore, in the
      presence of any extended connectivities contradictions can appear in the 2D NMR
      data. In this article, algorithmic methods for the detection and removal of
      contradictions in 2D NMR data that have been developed in support of StrucEluc
      are described. The methods are based on the analysis of molecular connectivity
      diagrams, MCDs. These methods have been implemented in the StrucEluc system and
      tested by solving 50 structural problems with 2D NMR spectral data containing
      contradictions. The presence of contradictions was detected by the algorithm in
      90% of the cases, and the contradictions were automatically removed in
      approximately 50% of the problems. A method of "fuzzy" structure generation in
      the presence of contradictions has been suggested and successfully tested in this
      work. This work will demonstrate examples of the application of developed methods
      to a number of structural problems.

PMID- 15446834
TI  - PROSIT: pseudo-rotational online service and interactive tool, applied to a
      conformational survey of nucleosides and nucleotides.
AB  - A Pseudo-Rotational Online Service and Interactive Tool (PROSIT) designed to
      perform complete pseudorotational analysis of nucleosides and nucleotides is
      described. This service is freely available at http://cactus.nci.nih.gov/prosit/.
      Files containing nucleosides/nucleotides or DNA/RNA segments, isolated or bound
      to other molecules (e.g., a protein) can be uploaded to be processed by PROSIT.
      The service outputs the pseudorotational phase angle P, puckering amplitude
      numax, and other related information for each nucleoside/nucleotide detected. The
      service was implemented using the chemoinformatics toolkit CACTVS. PROSIT was
      used for a survey of nucleosides contained in the Cambridge Structural Database
      and nucleotides in high-resolution crystal structures from the Nucleic Acid
      Database. Special cases discussed include nucleosides having constrained sugar
      moieties with extreme puckering amplitudes, and several specific DNA/RNA helices
      and protein-bound DNA oligonucleotides (Dickerson-Drew dodecamer, RNA/DNA hybrid
      viral polypurine tract, Z-DNA enantiomers, B-DNA containing (L)-alpha
      threofuranosyl nucleotides, TATA-box binding protein/TATA-box complex, and DNA
      (cytosine C5)-methyltransferase complexed with an oligodeoxyribonucleotide
      containing transition state analogue 5,6-dihydro-5-azacytosine). When the
      puckering amplitude decreases to a small value, the sugar becomes increasingly
      planar, thus reducing the significance of the phase angle P. We introduce the
      term "central conformation" to describe this part of the pseudorotational
      hyperspace in contrast to the conventional north and south conformations.

PMID- 15446835
TI  - Prediction of noninteractive mixture toxicity of organic compounds based on a
      fuzzy set method.
AB  - Current methods for the prediction of mixture toxicity have shown to be valid for
      mixtures that conform to some assumptions that were ideally formulated for
      mixtures comprising constituents exhibiting either completely similar or
      dissimilar mechanisms of action. Approaches are needed that predict the toxicity
      of mixtures representative of real environmental occurrences i.e., those
      comprising constituents of mixed similar and dissimilar compounds and therefore
      are more complex. In this paper such a methodology is proposed which uses
      molecular descriptors and fuzzy set theory to characterize the degree of
      similarity and dissimilarity of mixture constituents, integrates the
      concentration addition and independent action models, and therefore is called
      INFCIM (INtegrated Fuzzy Concentration addition--Independent action Model).
      INFCIM is tested in two case studies using toxicity data of four mixtures, and
      its performance is compared against those of both concentration addition and
      independent action models. Mixture 1 consists of 18 s-triazines acting on green
      freshwater algae scenedemus vacuolatus. Mixture 2 comprises 16 acting
      constituents tested on scenedemus vacuolatus. Both mixtures inhibit reproduction
      in the biological assays. There are 10 quinolone compounds in mixture 3 and 16
      phenol derivative compounds in mixture 4 all causing long-term inhibition of
      bioluminescence in the marine bacterium Vibrio fischeri. It was shown that INFCIM
      performed comparably or better than the best performing existing model in the
      original studies for all the mixtures tested.

PMID- 15446836
TI  - Novel receptor surface approach for 3D-QSAR: the weighted probe interaction
      energy method.
AB  - A 3D-QSAR technique, called the WeP (weighted probe interaction energy) method,
      has been developed based on the notion that certain regions of the receptor
      surface contribute, to varying extents, to the differences in the activities of
      the ligands, while other regions do not. The probes, placed around the surface of
      a superimposed set of ligands, were associated with fractional weights, and then
      an optimal distribution of probe weights that accounts for the activity profile
      of the training ligands was determined using a genetic algorithm. It has been
      shown for the three test samples that the pseudoreceptors, which consist of the
      surviving probes with nonzero weight values, have good predictabilities.
      Especially, in the case of dihydrofolate reductase inhibitors, the pseudoreceptor
      resembles the real protein in that there is no surviving probe in the solvent
      exposed region.

PMID- 15446837
TI  - Molecular dynamics simulation of the LOV2 domain from Adiantum capillus-veneris.
AB  - The mechanism for signal transduction from the LOV-domains toward the kinase
      region of phototropin is still not well understood. We have performed molecular
      dynamics (MD) simulations and CONCOORD calculations on the LOV2 domain of
      Adiantum capillus-veneris, with the goal to detect possible differences between
      the two forms of the LOV domain which may not show up in the static crystal
      structures. Since no such clear differences are found in the MD simulations also,
      we suggest that the real, biologically active conformation of the LOV domain
      within the whole phototropin is different from the crystal structure of the
      isolated LOV domains. The MD simulations do offer, however, insight into details
      of the dynamics of the dark and illuminated LOV domains, which are discussed in
      the light of recent experiments.

PMID- 15446838
TI  - Validated QSAR prediction of OH tropospheric degradation of VOCs: splitting into
      training-test sets and consensus modeling.
AB  - The rate constant for hydroxyl radical tropospheric degradation of 460
      heterogeneous organic compounds is predicted by QSAR modeling. The applied
      Multiple Linear Regression is based on a variety of theoretical molecular
      descriptors, selected by the Genetic Algorithms-Variable Subset Selection (GA
      VSS) procedure. The models were validated for predictivity by both internal and
      external validation. For the external validation two splitting approaches, D
      optimal Experimental Design and Kohonen Artificial Neural Networks (K-ANN), were
      applied to the original data set to compare the two methodologies. We emphasize
      that external validation is the only way to establish a reliable QSAR model for
      predictive purposes. Predicted data by consensus modeling from different models
      are also proposed.

PMID- 15446839
TI  - Application of the PharmPrint methodology to two protein kinases.
AB  - The PharmPrint methodology developed by McGregor and Muskal1,2 was used to
      construct quantitative structure-activity relationship (QSAR) models for the
      prediction of cyclin-dependent kinase-2 (CDK2) and vascular endothelial growth
      factor receptor-2 (VEGFR2) inhibition. The QSAR models were constructed based on
      a binary description of biological activity--a value of zero for inactive and one
      for active compounds. Subsets of "active" kinase inhibitors (that is, inhibitors
      with pIC50 > or = 6.0) along with a subset of MDDR3 compounds serving as the
      recommended set of inactive compounds were used for model development. The
      predicted activities for the training set compounds were in excellent agreement
      with the assigned binary activities with greater than 92% of the compounds
      correctly classified. However, when the QSAR models were applied to the subsets
      of "inactive" kinase inhibitors (that is, inhibitors with pIC50 < 6.0), greater
      than 67% were incorrectly predicted to be active. Identical results were obtained
      with our CDK2 and VEGFR2 validation sets, where the majority of the inactive
      kinase inhibitors were predicted to be active. In efforts to improve the
      predictive performance of the QSAR models, simple, but important modifications
      were made to the PharmPrint methodology. On the basis of these modifications, a
      second set of QSAR models was constructed and applied to our validation sets to
      assess their predictive performance. Significant improvements were seen with the
      modified version of PharmPrint over the original. The results from both versions
      of PharmPrint are compared and discussed.

PMID- 15446840
TI  - Defining privileged reagents using subsimilarity comparison.
AB  - We have developed a new method for assigning a drug-like score to reagents. This
      algorithm uses topological torsion (TT) 2D descriptors to compute the
      subsimilarity of any given reagent to a substructural element of any compound in
      the CMC. The utility of this approach is demonstrated by scoring a test set of
      reagents derived from the "Comprehensive Survey of Combinatorial Library
      Synthesis: 2000" (J. Comb. Chem.). R-groups were extracted from the most-active
      compounds found in each of the reviewed libraries, and the distribution of the
      subsimilarity scores for these monomers were compared to the ACD. This comparison
      showed a dramatic shift in the distribution of the JCC R-group subset toward
      higher subsimilarity scores in comparison to the entire ACD database. The ACD was
      also used to examine the relationship between molecular weight and various
      subsimilarity scoring algorithms. This analysis was used to derive a
      subsimilarity score that is less biased by molecular weight.

PMID- 15446842
TI  - A comparative study on feature selection methods for drug discovery.
AB  - Feature selection is frequently used as a preprocessing step to machine learning.
      The removal of irrelevant and redundant information often improves the
      performance of learning algorithms. This paper is a comparative study of feature
      selection in drug discovery. The focus is on aggressive dimensionality reduction.
      Five methods were evaluated, including information gain, mutual information, a
      chi2-test, odds ratio, and GSS coefficient. Two well-known classification
      algorithms, Naive Bayesian and Support Vector Machine (SVM), were used to
      classify the chemical compounds. The results showed that Naive Bayesian benefited
      significantly from the feature selection, while SVM performed better when all
      features were used. In this experiment, information gain and chi2-test were most
      effective feature selection methods. Using information gain with a Naive Bayesian
      classifier, removal of up to 96% of the features yielded an improved
      classification accuracy measured by sensitivity. When information gain was used
      to select the features, SVM was much less sensitive to the reduction of feature
      space. The feature set size was reduced by 99%, while losing only a few percent
      in terms of sensitivity (from 58.7% to 52.5%) and specificity (from 98.4% to
      97.2%). In contrast to information gain and chi2-test, mutual information had
      relatively poor performance due to its bias toward favoring rare features and its
      sensitivity to probability estimation errors.

PMID- 15446841
TI  - Comparison of 2D similarity and 3D superposition. Application to searching a
      conformational drug database.
AB  - In a database of about 2000 approved drugs, represented by 10(5) structural
      conformers, we have performed 2D comparisons (Tanimoto coefficients) and 3D
      superpositions. For one class of drugs the correlation between structural
      resemblance and similar action was analyzed in detail. In general Tanimoto
      coefficients and 3D scores give similar results, but we find that 2D similarity
      measures neglect important structural/funtional features. Examples for both over-
      and underestimation of similarity by 2D metrics are discussed. The required
      additional effort for 3D superpositions is assessed by implementation of a fast
      algorithm with a processing time below 0.01 s and a more sophisticated approach
      (0.5 s per superposition). According to the improvement of similarity detection
      compared to 2D screening and the pleasant rapidity on a desktop PC, full-atom 3D
      superposition will be an upcoming method of choice for library prioritization or
      similarity screening approaches.

PMID- 15446843
TI  - Insights into phenylalanine derivatives recognition of VLA-4 integrin: from a
      pharmacophoric study to 3D-QSAR and molecular docking analyses.
AB  - The very late antigen-4 (VLA-4), also known as integrin alpha4beta1, is expressed
      on monocytes, T- and B-lympohocytes, basophils, and eosinophils and is involved
      in the massive recruitment of granulocytes in different pathological conditions
      such as multiple sclerosis and asthma. VLA-4 interacts with its endogenous ligand
      VCAM-1 during chronic inflammation, and blockade of VLA-4 /VCAM-1 interaction is
      a potential target for immunosuppression. Two classes of VLA-4 antagonists have
      so far been reported: beta-amino acid derivatives containing a diaryl urea moiety
      (BIO-1211) and phenylalanine derivatives (TR-14035). With the aim of clarifying
      the structural basis responsible for VLA-4 recognition by phenylalanine
      derivatives, we developed a combined computational study on a set of 128
      antagonists available through the literature. Our computational approach is
      composed of three parts. (i) A VCAM-1 based pharmacophore was constructed with a
      restricted number of phenylalanine derivatives to identify the region of the
      protein that resembles synthetic antagonists. The pharmacophore was instrumental
      in constructing an alignment of a set of 128 compounds. This alignment was
      exploited to build a pseudoreceptor model with the RECEPTOR program. (ii) 3D-QSAR
      analysis was carried out on the computed electrostatic and steric interaction
      energies with the pseudoreceptor surface. The 3D-QSAR analysis yielded a
      predictive model able to explain much of the variance of the 128 antagonists.
      (iii) A homology modeling study of the headpiece of VLA-4 based on the crystal
      structure of alphavbeta3 was performed. Docking experiments of TR-14035 into the
      binding site of VLA-4 aided the interpretation of the 3D-QSAR model. The obtained
      results will be fruitful for the design of new potent and selective antagonists
      of VLA-4.

PMID- 15446844
TI  - Enhancing the effectiveness of virtual screening by fusing nearest neighbor
      lists: a comparison of similarity coefficients.
AB  - This paper evaluates the effectiveness of various similarity coefficients for 2D
      similarity searching when multiple bioactive target structures are available.
      Similarity searches using several different activity classes within the MDL Drug
      Data Report and the Dictionary of Natural Products databases are performed using
      BCI 2D fingerprints. Using data fusion techniques to combine the resulting
      nearest neighbor lists we obtain group recall results which, in many cases, are a
      considerable improvement on standard average recall values obtained for
      individual structures. It is shown that the degree of improvement can be related
      to the structural diversity of the activity class that is searched for, the best
      results being found for the most diverse groups. The group recall of active
      compounds using subsets of the class is also investigated: for highly self
      similar activity classes, the group recall improvement saturates well before the
      full activity class size is reached. A rough correlation is found between the
      relative improvement using the group recall and the square of the number of
      unique compounds available in all of the merged lists. The Tanimoto coefficient
      is found unambiguously to be the best coefficient to use for the recovery of
      active compounds using multiple targets. Furthermore, when using the Tanimoto
      coefficient, the "MAX" fusion rule is found to be more effective than the "SUM"
      rule for the combination of similarity searches from multiple targets. The use of
      group recall can lead to improved enrichment in database searches and virtual
      screening.

PMID- 15446845
TI  - Influenza virus neuraminidase inhibitors: generation and comparison of structure
      based and common feature pharmacophore hypotheses and their application in
      virtual screening.
AB  - X-ray crystallographic data of the influenza virus neuraminidase in complex with
      different inhibitors were used to generate chemical feature-based pharmacophore
      models of the binding site of this enzyme. The models were built using the
      software package Catalyst. Pharmacophore hypotheses derived from the 3-D
      structure of ligands cocrystallized with the enzyme were then compared with
      automatically generated common feature pharmacophore hypotheses for neuraminidase
      inhibitors. The latter models were found to contain fewer features and exhibited
      lower selectivity in virtual screening experiments. Some functions of the
      inhibitors obviously participate in more than one mode of interaction with the
      enzyme (charge-charge interaction and hydrogen bond) or form hydrogen bonds to
      several amino acids. Since such multiple interactions of one chemical function
      cannot be included into the Catalyst data format, strategies are presented to
      overcome these limitations. Finally, the results of 3-D database searching
      experiments using these hypotheses are described.

PMID- 15446846
TI  - A ligand-based molecular modeling study on some matrix metalloproteinase-1
      inhibitors using several 3D QSAR techniques.
AB  - Some three-dimensional quantitative structure-activity relationship (3D-QSAR)
      models have been constructed using the comparative molecular field analysis
      (CoMFA) and comparative molecular similarity indices (CoMSIA) for a series of 84
      proline-based plus 12 structurally more diversified nonproline matrix
      metalloproteinase inhibitors. The structures of these inhibitors were built from
      a structure template extracted from the crystal structure of stromelysin. The
      structures built were divided into the training and test sets for both the CoMFA
      and CoMSIA analyses for each being composed of 60 and 24 inhibitors,
      respectively. The structures in the training set were aligned using some
      alignment rules derived from the analysis of the Ligplot program on a recent
      crystal structure of ligand-collagenase-1 complex. Some stepwise CoMSIA's were
      performed on the aligned training set on which the best CoMFA result was
      obtained. The best CoMSIA model was identified from the stepwise results, and the
      corresponding pharmacophore features were used for the construction of a
      pharmacophore hypothesis by the Catalyst 4.9 program. The training set was
      extended to include 11 structurally more diversified and nonproline inhibitors.
      To construct a pharmacophore hypothesis, the conformation of 60 structurally
      aligned proline-based inhibitors was fixed, while that of the 11 structurally
      more diversified nonproline inhibitors was allowed to vary during the hypothesis
      construction process. It was found that the predicted activities by the top
      hypothesis constructed for both the training and test sets were as good in
      statistics as those predicted by the best CoMSIA model from which the hypothesis
      was derived. The top hypothesis was mapped onto the structures of several highly
      active inhibitors selected from both the training and test sets. The goodness of
      mapping on each inhibitor was found to be correlated well with the activity of
      each inhibitor.

PMID- 15446847
TI  - Enzyme binding selectivity prediction: alpha-thrombin vs trypsin inhibition.
AB  - In the present work we explore the possibility of an in-depth computational
      analysis of available experimental X-ray structures in the specific case of a
      series of alpha-thrombin and trypsin complexes with their respective inhibitors
      for the development of a novel scoring function based on molecular electrostatic
      potential computed at the contact surface in the enzyme-inhibitor molecular
      complex. We subsequently employ the chemometrical approach to determine which are
      the interactions in the large volume of data that determine the resulting
      experimental binding constant between ligand and receptor. The results of the
      model evaluated with molecules in the independent validation set show that a
      reasonable average error of 1.30 log units of the difference between experimental
      and calculated binding constants was achieved in the system thrombin-trypsin,
      which is comparable with those of methods from the literature. Furthermore, by a
      careful preparation of the Kohonen top layer in the artificial neural network
      approach that is normally perceived as a "black box device", we have been able to
      follow the implications of the structure of the inhibitor-enzyme complex for the
      inhibitor's binding constant. The method appears to be suitable for evaluation of
      selectivity in structurally similar enzymatic systems, which is currently an
      important problem in drug design.

PMID- 15446849
TI  - Personal experience with four kinds of chemical structure drawing software:
      review on ChemDraw, ChemWindow, ISIS/Draw, and ChemSketch.

PMID- 15446848
TI  - The Merck index 13.2 CD-ROM edition from CambridgeSoft.

PMID- 15446850
TI  - Nonclassical bonding in the novel structure of Ba2Bi3 and unexpected site
      preference in the coloring variant Ba2BiSb2.
AB  - The new phase Ba(2)Bi(3) crystallizes in the W(2)CoB(2) structure type. Its
      structure contains rigorously planar anionic layers of (4.6.4.6)(4.6(2))(2) nets
      with three- and four-bonded Bi, that are separated by Ba atoms. An unexpected
      site preference is observed in the coloring variant Ba(2)BiSb(2) with Sb
      occupying only the three-bonded sites. The nonclassical bonding in the anionic
      network can be rationalized from a reformulation of the Zintl concept as
      (Ba(2+))(2)[Bi(3)](3)(-)(e(-)). Bonding distances suggest that the extra electron
      fills Bi-Bi antibonding states. The densities of states obtained from TB-LMTO-ASA
      calculations show metallic character for both compounds.

PMID- 15446851
TI  - Synthesis, structures, and solution behavior of di- and trinuclear titanium(IV)-
      cyclophosphato complexes.
AB  - The reaction of the cyclotetraphosphate ion (P(4)O(12)(4)(-)) with [CpTiCl(3)]
      (Cp = eta(5)-C(5)Me(5)) gives [(CpTi)(2)(P(4)O(12))(2)](2)(-) where the P(4)O(12)
      ligands adopt a saddle conformation, while that with [(CpTiCl)(3)(mu-O)(3)] leads
      to [(CpTi)(3)(mu-O)(3)(P(4)O(12))](-) containing a crown form P(4)O(12) ligand;
      both products feature their unique cage structures. On the other hand, the
      reactions of the cyclotriphosphate ion (P(3)O(9)(3)(-)) with [(CpTiCl(2))(2)(mu
      O)] and [(CpTiCl)(3)(mu-O)(3)] afford [(CpTi)(2)(mu-O)(P(3)O(9))(2)](2)(-) and
      [(CpTi)(3)(mu-O)(3)Cl(P(3)O(9))](-), respectively, and in both cases the P(3)O(9)
      ligands bridge two titanium centers with an eta(2):eta(1) mode.

PMID- 15446852
TI  - Unprecedented acceleration of zirconium(IV)-assisted peptide hydrolysis at
      neutral pH.
AB  - 4,13-Diaza-18-crown-6 substantially increases the rate of zirconium(IV)
      hydrolysis of unactivated peptide amide bonds under near-physiological conditions
      of temperature and pH. In the presence of this azacrown ether, ZrCl(4)
      efficiently hydrolyses both neutral and negatively charged peptides (pH 7.0-7.3,
      37-60 degrees C).

PMID- 15446853
TI  - Synthesis and characterization of a tetrazolate-bridged coordination framework
      encapsulating D2h-symmetric cyclic (H2O)4 cluster arrays.
AB  - Reaction of 5,5'-(1,4-phenylene)bis(1H-tetrazole), which was prepared in two
      steps, with cadmium nitrate in DMF produced a three-dimensional framework with
      one-dimensional channels (35% void volume), in which unprecedented hydrogen-bond
      supported D(2)(h)() tetrameric cyclic water clusters ranked.

PMID- 15446854
TI  - Halogeno-coordinated iron corroles.
AB  - The first full assignment of (1)H NMR chemical shifts for iron corroles and the
      first synthesis of a series of (halogeno)iron corroles reveal very large effects
      of the axial ligands on the corresponding spectra, which apparently reflect
      differences in the relative importance of metal-to-corrole and corrole-to-metal
      pi-donation. These findings pave the way for a thorough analysis of the
      electronic structures of such complexes.

PMID- 15446855
TI  - Dynamic coordination polymers with 4,4'-oxybis(benzoate): reversible
      transformations of nano- and nonporous coordination frameworks responding to
      present solvents.
AB  - Reversible construction of a nanoporous framework from a nonporous framework has
      been found in the zinc(II) coordination polymer with 4,4'-oxybis(benzoate) (oba).
      [Zn(2)(oba)(2)(dmf)(2)].2DMF (1), which has 1 nm scale channels, transforms to
      the nonporous coordination polymer [Zn(oba)(H(2)O)] (2) with the loss of the open
      framework. Compound 2 on treatment with DMF reversibly yields nanoporous compound
      1.

PMID- 15446856
TI  - Cooperative formation of trinuclear zinc(II) complexes via complexation of a
      tetradentate oxime chelate ligand, salamo, and zinc(II) acetate.
AB  - Novel trinuclear zinc(II) complexes [Zn(3)L(2)(OAc)(2)] (L = salamo, 3-MeOsalamo)
      were synthesized, and their structures were determined by X-ray crystallography.
      Ligation of methoxy groups in the salamo ligand causes a significantly different
      coordination mode of the central zinc atom in the trinuclear system. The
      complexes between the salamo ligands and zinc(II) in methanol formed exclusively
      and very cooperatively. In contrast to other imine ligands, the mononuclear [ZnL]
      and other complexes are not observed at all.

PMID- 15446857
TI  - Structural variability in neptunium(V) oxalate compounds: synthesis and
      structural characterization of Na2NpO2(C2O4)OH.H2O.
AB  - Reaction of a (237)Np(V) stock solution in the presence of oxalic acid, calcium
      chloride, and sodium hydroxide under hydrothermal conditions produces single
      crystals of a neptunium(V) oxalate, Na(2)NpO(2)(C(2)O(4))OH.H(2)O. The structure
      consists of one-dimensional chains running down the a axis and is the first
      example of a neptunium(V) oxalate compound containing hydroxide anions.

PMID- 15446858
TI  - K2[Ge(B4O9)].2H2O: a unique 3D alternating linkage mode of a B4O9 cluster and
      GeO4 unit in borogermanate with two pairs of interweaving double helical
      channels.
AB  - The first noncentrosymmetric potassium templated borogermanate,
      K(2)[Ge(B(4)O(9))].2H(2)O, has been solvothermally synthesized and characterized
      by IR, SEM, powder X-ray diffraction (PXRD), TGA, energy dispersive spectroscopy
      (EDS), single crystal X-ray diffraction, and second harmonic generation (SHG)
      activity, respectively. This compound crystallized in the monoclinic space group
      Cc with a = 6.793(1) A, b = 12.0699(3) A, c = 11.895(3) A, beta = 91.156(4)
      degrees, V = 975.1(4) A(3), and Z = 4. Interestingly, the structure possesses a
      unique 3D alternating linkage mode of B(4)O(9) clusters and GeO(4) units and
      contains two pairs of interweaving double helical channels with a 10-membered
      ring. In one, the right- and left-handed helices couple each other, and in the
      other, the left- and right-handed helices couple together. The compound exhibits
      distinct nonlinear optical (NLO) properties because it lacks a symmetric center.
      Furthermore, the framework of the title compound not only displays high thermal
      stability but also can be recoverable to a large degree during a dehydration
      hydration cycle.

PMID- 15446859
TI  - The Nowotny chimney ladder phases: following the c(pseudo) clue toward an
      explanation of the 14 electron rule.
AB  - We account for two empirical rules of the Nowotny chimney ladder phases (NCLs,
      intermetallic compounds of the form T(t)E(m); T, groups 4-9; E, groups 13-15).
      The first rule is that for late transition metal NCLs the total number of valence
      electrons per T atom is 14. The second is the appearance of a pseudoperiodicity
      with a spacing, c(pseudo), which is directly related to the stoichiometry,
      T(t)E(m), by (2t - m) c(pseudo)= c. Both rules are accounted for by viewing the
      NCLs as twinned structures constructed from blocks of the parent compound,
      RuGa(2) of thickness c(pseudo)/2, with the successive layers rotated relative to
      each other by 90 degrees. Sterically encumbered E atoms are then deleted at the
      interfaces between layers, followed by relaxation.

PMID- 15446860
TI  - The Nowotny chimney ladder phases: whence the 14 electron rule?
AB  - The late transition metal Nowotny chimney ladder phases (NCLs, T(t)E(m); T,
      groups 7-9; E, groups 13 and 14) follow a 14 electron rule: the total number of
      valence electrons per T atom is 14. In this paper, we extract a chemical
      explanation for this rule from extended Huckel calculations; we focus on RuGa(2),
      the parent NCL structure. A gap between filled and unfilled bands arises from the
      occupation of two Ga-Ga bonding/Ru-Ga nonbonding orbitals per RuGa(2),
      independent of k-point. In addition, the five Ru d levels are filled. Together
      this makes for 7 filled bands at each k-point, or 14 electrons per Ru. We discuss
      the connections between this 14 electron rule and the 18 electron rule of
      organometallic complexes.

PMID- 15446861
TI  - Mono- and dinuclear complexes of chiral tri- and tetradentate Schiff-base ligands
      derived from 1,1'-binaphthyl-2,2'-diamine.
AB  - The synthesis and characterization of the bis(bidentate) Schiff-base ligand [(R)
      2] formed by the condensation reaction of (R)-1,1'-binaphthyl-2,2'-diamine [(R)
      BINAM] with pyridine-2-carboxaldehyde is presented. The coordination chemistry of
      (R)-2 with Ni(ClO(4))(2).6H(2)O, Co(ClO(4))(2).6H(2)O, CuCl(2), and CuSO(4) has
      been investigated. Reaction of (R)-2 with the first two metal salts leads to
      complexes of the type [M((R)-4)(2)](ClO(4))(2) (M = Ni(II), Co(II)), where (R)-4
      is a tridentate ligand resulting from the hydrolytic cleavage of one of the
      pyridyl groups from (R)-2. Both complexes were characterized by X-ray
      crystallography, which showed that the Lambda absolute configuration of the metal
      center is favored in both cases. (1)H NMR spectroscopy suggests that the high
      diastereoselectivity of Lambda-[Co((R)-4)(2)](ClO(4))(2) is maintained in
      solution. The reaction of (R)-2 with CuCl(2) leads to the dinuclear complex
      [Cu(2)((R)-2)Cl(4)], which has a [Cu(2)(mu(2)-Cl(2))] core. The reaction of
      CuSO(4) with (R)-2 gives a dimeric complex, [Cu((R)-4)SO(4)](2), which features a
      [Cu(2)(mu(2)-(SO(4))(2))] core. This complex can be prepared directly by the
      reaction of (R)-BINAM with pyridine-2-carboxaldehyde and CuSO(4). The use of rac
      BINAM in this synthetic procedure leads to the heterochiral dimer [Cu(2)((R)
      4)((S)-4)(SO(4))(2)]; that is, the ligands undergo a self-sorting (self/nonself
      discrimination) process based on chirality. The reaction of rac-BINAM, pyridine-2
      carboxaldehyde, and Co(ClO(4))(2).6H(2)O proceeds via a homochiral self-sorting
      pathway to produce a racemic mixture of [Co((R)-4)(2)](2+) and [Co((S)
      4)(2)](2+). The variable-temperature magnetic susceptibilities of the bimetallic
      complexes [Cu(2)((R)-2)Cl(4)], [Cu((R)-4)(mu(2)-SO(4))](2), and [Cu(2)((R)-4)((S)
      4)(mu(2)-SO(4))(2)] all show weak antiferromagnetic coupling with J = -1.0, 
      0.40, and -0.67 cm(-)(1), respectively.

PMID- 15446862
TI  - Binding of DNA purine sites to dirhodium compounds probed by mass spectrometry.
AB  - The adducts formed between the antitumor active compounds
      [Rh(2)(O(2)CCH(3))(2)(CH(3)CN)(6)](BF(4))(2), Rh(2)(O(2)CCH(3))(4), and
      Rh(2)(O(2)CCF(3))(4) with DNA oligonucleotides have been assessed by matrix
      assisted laser desorption ionization (MALDI) and nanoelectrospray (nanoESI)
      coupled to time-of-flight mass spectrometry (TOF MS). A series of MALDI studies
      performed on dipurine (AA, AG, GA, and GG)-containing single-stranded
      oligonucleotides of different lengths (tetra- to dodecamers) led to the
      establishment of the relative reactivity cis-[Pt(NH(3))(2)(OH(2))(2)](2+)
      (activated cisplatin) approximately Rh(2)(O(2)CCF(3))(4) > cis
      [Pt(NH(3))(2)Cl(2)] (cisplatin) >> [Rh(2)(O(2)CCH(3))(2)(CH(3)CN)(6)](BF(4))(2) >
      Rh(2)(O(2)CCH(3))(4) approximately Pt(C(6)H(6)O(4))(NH(3))(2) (carboplatin). The
      relative reactivity of the complexes is associated with the lability of the
      leaving groups. The general trend is that an increase in the length of the
      oligonucleotide leads to enhanced reactivity for
      Rh(2)(O(2)CCH(3))(2)(CH(3)CN)(6)](BF(4))(2) and Rh(2)(O(2)CCH(3))(4) (except for
      the case of [Rh(2)(O(2)CCH(3))(2)(CH(3)CN)(6)](2+), which reacts faster with the
      GG octamers than with the dodecamers), whereas the reactivity of
      Rh(2)(O(2)CCF(3))(4) is independent of the oligonucleotide length. When monitored
      by ESI, the dodecamers containing GG react faster than the respectiveAA
      oligonucleotides in reactions with Rh(2)(O(2)CCF(3))(4) and
      Rh(2)(O(2)CCH(3))(2)(CH(3)CN)(6)](BF(4))(2), whereas AA oligonucleotides react
      faster with Rh(2)(O(2)CCH(3))(4). The mixed (AG, GA) purine sequences exhibit
      comparable rates of reactivity with the homopurine (AA, GG) dodecamers in
      reactions with Rh(2)(O(2)CCH(3))(4). The observation of initial dirhodium-DNA
      adducts with weak axial (ax) interactions, followed by rearrangement to more
      stable equatorial (eq) adducts, was achieved by electrospray ionization; the Rh
      Rh bond as well as coordinated acetate or acetonitrile ligands remain intact in
      these dirhodium-DNA adducts. MALDI in-source decay (ISD), collision-induced
      dissociation (CID) MS-MS, and enzymatic digestion studies followed by MALDI and
      ESI MS reveal that, in the dirhodium compounds studied, the purine sites of the
      DNA oligonucleotides interact with the dirhodium core. Ultimately, both MALDI and
      ESI MS proved to be complementary, valuable tools for probing the identity and
      stability of dinuclear metal-DNA adducts.

PMID- 15446863
TI  - Metal-metal bonding in ScTaN2. A new compound in the system ScN-TaN.
AB  - Gray microcrystalline powders of ScTaN(2) were prepared from solid-state
      reactions of delta-ScN with Ta(3)N(5) powders at T = 1770 K. According to thermal
      analyses the compound is stable against oxidation by O(2) up to temperatures of T
      = 800 K. In an Ar atmosphere ScTaN(2) decomposes above T = 1250 K and in a N(2)
      atmosphere above T = 2000 K under release of N(2) to form delta-ScN and beta
      Ta(2)N. The crystal structure (space group P6(3)/mmc, No. 194, a = 305.34(3) pm,
      c = 1056.85(9) pm, Z = 2) was refined on the basis of X-ray and neutron powder
      diffraction data. It comprises alternating layers of ScN(6/3) octahedra and
      trigonal TaN(6/3) prisms, which are also observed in the binary nitrides delta
      ScN and theta-TaN, respectively. A small degree of anti-site defects (about 5%)
      was detected. Only a small solubility of ScN in epsilon-TaN was observed, while
      the solubility of TaN in delta-ScN is >/=10 mol % at T = 1820 K. ScTaN(2) is a
      diamagnetic small gap semiconductor or a semimetal, as inferred from
      magnetization and electrical resistivity measurements, consistent with band
      structure calculations. Chemical bonding analyses with the COHP method yield
      significant covalent Ta-Ta interactions. Topological analyses of the electron
      localization function reveal unexpected Ta-Ta three-center bonding basins within
      seemingly empty trigonal prisms of the TaN(6/3) layers.

PMID- 15446864
TI  - Design and study of Bi[1,8]naphthyridine ligands as potential photooxidation
      mediators in Ru(II) polypyridyl aquo complexes.
AB  - A series of 3,3'-polymethylene-bridged bi[1,8]naphthyridine (binap) ligands, 3a
      c, are complexed with Ru(II) to afford [Ru(tpy)(3a-c)(H(2)O)](2+) where an
      uncomplexed nitrogen on 3a-c is situated so it can form a H-bond with the
      coordinated water. An additional complex involving [Ru(4'
      NMe(2)tpy)(3b)(H(2)O)](2+) is also prepared. X-ray analyses of the
      [Ru(tpy)(3a,c)(H(2)O)](2+) complexes indicate well-organized H-bonds even when
      the binap is nonplanar. In an attempt to realize photooxidation, the effects of
      light, varying potential, and pH were examined. A Pourbaix diagram indicated that
      the oxidation potential decreased by approximately 0.5 V in the pH range of 1.9
      11.6. The lowest-energy electronic absorption for the binap complexes involves
      the metal-to-ligand charge transfer to the binap ligand and is sensitive to
      ligand planarity. The absorbance shifted to a lower energy as the auxiliary
      ligand became a better donor (4'-NMe(2)tpy) or as the water was deprotonated.
      Acetonitrile was found to displace water most easily for the complex of 3c, where
      the ligand is the least planar. Despite promising features, photooxidation of the
      bound water was not observed.

PMID- 15446865
TI  - Mononuclear, five-coordinate lanthanide amido and aryloxide complexes bearing
      tetradentate (N2O2) Schiff bases.
AB  - Two monomeric, five-coordinate lanthanide complexes, [bis-5,5'-(1,3
      propanediyldiimino)-2,2-dimethyl-4-hexene-3-onato]samarium[2,6-bis(tert-butyl)-4
      methylphenoxide] and [bis-5,5'-(1,3-propanediyldiimino)-2,2-dimethyl-4-hexene-3
      onato]erbium[2,6-bis(tert-butyl)-4-methylphenoxide], were isolated from the
      reactions of 2,6-bis(tert-butyl)-4-methylphenol with [bis-5,5'-(1,3
      propanediyldiimino)-2,2-dimethyl-4-hexene-3
      onato]lanthanide[bis(trimethylsilyl)amido] (lanthanide = Er(3+) and Sm(3+)). The
      purified phenoxides were recovered in excellent yields and analytical purity, and
      the reactions proceeded cleanly without Schiff-base degradation or cluster
      formation. Analogously, [bis-3,3'-(1,3-propanediyldiimino)-1-phenyl-2-butene-1
      onato]erbium[bis(trimethylsilyl)amido] was also directly converted to [bis-3,3'
      (1,3-propanediyldiimino)-1-phenyl-2-butene-1-onato]erbium[2,6-bis(tert-butyl)-4
      methylphenoxide]; however, a less sterically demanding alcohol (i.e., ethanol)
      yielded a neutral trinuclear oxo alkoxide species with each dianionic Schiff base
      asymmetrically bridging through micro-oxo interactions. In this polynuclear
      cluster, each symmetry-related, seven-coordinate erbium(III) ion exhibits
      monocapped trigonal prismatic geometry, which assembles by sharing triangular
      capped faces. Single-crystal X-ray diffraction revealed square-pyramidal metal
      coordination in each five-coordinate lanthanide ion with varied S(4) ruffling of
      the "square base" donor atoms and the six-membered propylene diamine chelate ring
      adopting the boat conformation. To contrast the effect of subtle ligand changes,
      we also report the synthesis and characterization of [bis-5,5'-(2,2-dimethyl-1,3
      propanediyldiimino)-2,2-dimethyl-4-hexene-3
      onato]samarium[bis(trimethylsilyl)amido], having gem-dimethyl substituents
      appended to the propylene bridge central carbon. The six-membered diamine chelate
      ring in this compound adopts the chair conformation without metal-hydrocarbon
      interaction. Also presented are qualitative activity observations and
      polymerization data for the polymerization of rac-lactide and epsilon
      caprolactone using the five-coordinate lanthanide amidos and phenoxides.

PMID- 15446866
TI  - Synthesis, characterization, and detailed electrochemistry of binuclear
      ruthenium(III) complexes bridged by bisacetylacetonate. Crystal and molecular
      structures of [[Ru(acac)2]2(tae)] (acac = 2,4-pentanedionate ion, tae = 1,1,2,2
      tetraacetylethanate dianion).
AB  - Binuclear beta-diketonatoruthenium(III) complexes [[Ru(acac)(2)](2)(tae)],
      [[Ru(phpa)(2)](2)(tae)], and [(acac)(2)Ru(tae)Ru(phpa)(2)] and binuclear and
      mononuclear bipyridine complexes [[Ru(bpy)(2)](2)(tae)](PF(6))(2) and
      [Ru(bpy)(2)(Htae)]PF(6) (acac = 2,4-pentanedionate ion, phpa = 2,2,6,6
      tetramethyl-3,5-heptanedionate ion, tae = 1,1,2,2-tetraacetylethanate dianion,
      and bpy = 2,2'-bipyridine) were synthesized. The new complexes have been
      characterized by (1)H NMR, MS, and electronic spectral data. Crystal and
      molecular structures of [[Ru(acac)(2)](2)(tae)] have been solved by single
      crystal X-ray diffraction studies. Crystal data for the meso isomer of
      [[Ru(acac)(2)](2)(tae)] have been confirmed by the dihedral angle result that two
      acetylacetone units of the bridging tae ligand are almost perpendicular to one
      another. A detailed investigation on the electrochemistry of the binuclear
      complexes has been carried out. The electrochemical behavior details of the
      binuclear complexes have been compared with those of the mononuclear complexes
      obtained from the half-structures of the corresponding binuclear complexes.
      Studies on the effects of solvents on the mixed-valence states of Ru(II)-Ru(III)
      and Ru(III)-Ru(IV) complexes have been carried out by various voltammetric and
      electrospectroscopic techniques. A correlation between the comproportionation
      constant (K(c)) and the donor number of the solvent has been obtained. The K(c)
      values for the binuclear complexes have been found to be low because of the fact
      that two acetylacetone units of the bridging tae ligand are not in the same
      plane, as revealed by the crystal structure of [[Ru(acac)(2)](2)(tae)].

PMID- 15446867
TI  - Kinetics of acid-catalyzed O-atom transfer from a hydroperoxorhodium complex to
      organic and inorganic substrates.
AB  - Oxygen atom transfer from (NH(3))(4)(H(2)O)RhOOH(2+) to organic and inorganic
      nucleophiles takes place according to the rate law 
      d[(NH(3))(4)(H(2)O)RhOOH(2+)]/dt = k[H(+)]
      [(NH(3))(4)(H(2)O)RhOOH(2+)][nucleophile] for all the cases examined. The third
      order rate constants were determined in aqueous solutions at 25 degrees C for
      (CH(2))(5)S (k = 430 M(-)(2) s(-)(1), micro = 0.10 M), (CH(2))(4)S(2) (182, micro
      = 0.10 M), CH(3)CH(2)SH (8.0, micro = 0.20 M), (en)(2)Co(SCH(2)CH(2)NH(2))(2+)
      (711, micro = 0.20 M), and, in acetonitrile-water, CH(3)SPh (130, 10% AN, micro =
      0.20 M), PPh(3) (3.74 x 10(3), 50% AN), and (2-C(3)H(7))(2)S (45, 50% AN, micro =
      0.20 M). Oxidation of PPh(3) by (NH(3))(4)(H(2)O)Rh(18)O(18)OH(2+) produced
      (18)OPPh(3). The reaction with a series of p-substituted triphenylphosphines
      yielded a linear Hammett relationship with rho = -0.53. Nitrous acid (k = 891 M(
      )(2) s(-)(1)) is less reactive than the more nucleophilic nitrite ion (k = 1.54 x
      10(4) M(-)(2) s(-)(1)).

PMID- 15446868
TI  - Synthesis and characterization of novel monocarbollide exo-closo-(pi
      arene)biruthenacarboranes [(PPh3)mClRu(eta6-C6H5R)Ru'CB10H11-n(OMe)n] (where R =
      H, m = 2, n = 1; R = mu-PPh2, m = 1, n = 0, 1).
AB  - The monocarbon carborane [Cs][nido-7-CB(10)H(13)] reacts with the 16-electron
      [RuCl(2)(PPh(3))(3)] in a solution of benzene/methanol in the presence of
      N,N,N',N'-tetramethylnaphthalene-1,8-diamine as the base to give a series of 12
      vertex monocarbon arene-biruthenacarborane complexes of two types: [closo-2-[7,11
      exo-RuClPPh(3)(mu,eta(6)-C(6)H(5)PPh(2))]-7,11-(mu-H)(2)-2,1-RuCB(10)H(8)R] (5, R
      = H; 6, R = 6-MeO; 7, R = 3-MeO) and [closo-2-(eta(6)-C(6)H(6))-10,11,12-[exo
      RuCl(PPh(3))(2)]-10,11,12-(mu-H)(3)-2,1-RuCB(10)H(7)R(1)] (8a, R(1) = 6-MeO; 8b,
      R(1) = 3-MeO, inseparable mixture of isomers) along with trace amounts of 10
      vertex mononuclear hypercloso/isocloso-type complexes [2,2-(PPh(3))(2)-2-H-3,9
      (MeO)(2)-2,1-RuCB(8)H(7)] (9) and [2,5-(Ph(3)P)-2-Cl-2-H-3,9-(MeO)(2)-2,1
      RuCB(8)H(6)] (10). Binuclear ruthenacarborane clusters of both series were
      characterized by a combination of analytical and multinuclear NMR spectroscopic
      data and by single-crystal X-ray diffraction studies of three selected complexes,
      6-8. In solution, isomers 8a,b have been shown to undergo the isomerization
      process through the scrambling of the exo-[RuCl(PPh(3))(2)] fragment about two
      adjacent triangular cage boron faces B(7)B(11)B(12) and B(8)B(9)B(12).

PMID- 15446869
TI  - The ionic isomegethic rule and additivity relationships: estimation of ion
      volumes. A route to the energetics and entropics of new, traditional,
      hypothetical, and counterintuitive ionic materials.
AB  - By virtue of our recently established relationships, knowledge of the formula
      unit volume, V(m), of a solid ionic material permits estimation of thermodynamic
      properties such as standard entropy, lattice potential energy, and, hence,
      enthalpy and Gibbs energy changes for reactions. Accordingly, development of an
      approach to obtain currently unavailable ion volumes can expose compounds
      containing these ions to thermodynamic scrutiny, such as predictions regarding
      stability and synthesis. The isomegethic rule, introduced in this paper, states
      that the formula unit volumes, V(m), of isomeric ionic salts are approximately
      the same; this rule then forms the basis for a powerful and successful means of
      predicting unknown ion volumes (as well as providing a means of validating
      existing volume and density data) and, thereby, providing solid state
      thermodynamic data. The rule is exploited to generate unknown ion and (by
      additivity) corresponding formula unit volumes.

PMID- 15446870
TI  - Alfred Werner's inorganic counterparts of racemic and mesomeric tartaric acid: a
      milestone revisited.
AB  - Both isomers of [(en)(2)Co(micro-NO(2))(micro-NH(2))Co(en)(2)](4+) synthesized by
      Alfred Werner in 1913 have been optically resolved and are therefore the classic
      inorganic analogues of the sugars threose and erythrose, rather than the rac- and
      meso-tartaric acids, as Werner believed. The nitro bridge is unsymmetrically N-O
      bonded, and each dinuclear ion is therefore asymmetric, a fact also clearly
      apparent in the (1)H and (13)C NMR spectra.

PMID- 15446871
TI  - Zn(II) coordination to polyamine macrocycles containing dipyridine units. New
      insights into the activity of dinuclear Zn(II) complexes in phosphate ester
      hydrolysis.
AB  - Zn(II) binding by the dipyridine-containing macrocycles L1-L3 has been analyzed
      by means of potentiometric measurements in aqueous solutions. These ligands
      contain one (L1, L2) or two (L3) 2,2'-dipyridine units as an integral part of a
      polyamine macrocyclic framework having different dimensions and numbers of
      nitrogen donors. Depending on the number of donors, L1-L3 can form stable mono-
      and/or dinuclear Zn(II) complexes in a wide pH range. Facile deprotonation of
      Zn(II)-coordinated water molecules gives mono- and dihydroxo-complexes from
      neutral to alkaline pH values. The ability of these complexes as nucleophilic
      agents in hydrolytic processes has been tested by using bis(p-nitrophenyl)
      phosphate (BNPP) as a substrate. In the dinuclear complexes the two metals play a
      cooperative role in BNPP cleavage. In the case of the L2 dinuclear complex
      [Zn(2)L2(OH)(2)](2+), the two metals act cooperatively through a hydrolytic
      process involving a bridging interaction of the substrate with the two Zn(II)
      ions and a simultaneous nucleophilic attack of a Zn-OH function at phosphorus; in
      the case of the dizinc complex with the largest macrocycle L3, only the
      monohydroxo complex [Zn(2)L3(OH)](3+) promotes BNPP hydrolysis. BNPP interacts
      with a single metal, while the hydroxide anion may operate a nucleophilic attack.
      Both complexes display high rate enhancements in BNPP cleavage with respect to
      previously reported dizinc complexes, due to hydrophobic and pi-stacking
      interactions between the nitrophenyl groups of BNPP and the dipyridine units of
      the complexes.

PMID- 15446872
TI  - pH-dependent isolations and spectroscopic, structural, and thermal studies of
      titanium citrate complexes.
AB  - Titanium(IV) citrate complexes (NH(4))(2)[Ti(H(2)cit)(3)].3H(2)O (1),
      (NH(4))(5)[Fe(H(2)O)(6)][Ti(H(2)cit)(3)(Hcit)(3)Ti].3H(2)O (2),
      Ba(2)[Ti(H(2)cit)(Hcit)(2)].8H(2)O (3), and
      Ba(3)(NH(4))(7)[Ti(cit)(3)H(3)(cit)(3)Ti].15H(2)O (4) (H(4)cit = citric acid)
      were isolated in pure form from the solutions of titanium(IV) citrate with
      various countercations. The isolated complexes were characterized by elemental
      analyses, IR spectra, and (1)H NMR and (13)C NMR spectra. The formation of
      titanium(IV) citrate complexes depends mainly on the pH of the solutions, that
      is, pH 1.0-2.8 for the formation of ammonium titanium(IV) citrate 1, pH 2.5-3.5
      for ammonium iron titanium(IV) citrate 2, pH 2.8-4.0 for dibarium titanium(IV)
      citrate 3, and pH 5.0-6.0 for ammonium barium titanium(IV) citrate 4. X-ray
      structural analyses revealed that complexes 2-4 featured three different
      protonated forms of bidentate citrate anions that chelate to the titanium(IV)
      atom through their negatively charged alpha-alkoxyl and alpha-carboxyl oxygen
      atoms. This is consistent with the large downfield shifts of the (13)C NMR
      spectra for the carbon atoms bearing the alpha-alkoxyl and alpha-carboxyl groups.
      The typical coordination modes of the barium atoms in complexes 3 and 4 are six
      coordinated, with three alpha-alkoxyl groups and three beta-carboxyl groups of
      citrate ions. The strong hydrogen bonding between the beta-carboxylic acid and
      the beta-carboxyl groups [2.634(8) A for complex 2, 2.464(7) A for complex 3, and
      2.467(7) A for complex 4] may be the key factor for the stabilization of the
      citrate complexes. The decomposition of complex 3 results in the formation of a
      pure dibarium titanate phase and 4 for the mixed phases of dibarium titanate and
      barium titanate at 1000 degrees C.

PMID- 15446873
TI  - Iron chelation properties of an extracellular siderophore exochelin MS.
AB  - The coordination chemistry of an extracellular siderophore produced by
      Mycobacterium smegmatis, exochelin MS (ExoMS), is reported along with its pK(a)
      values, Fe(III) and Fe(II) chelation constants, and aqueous solution speciation
      as determined by spectrophotometric and potentiometric titrations. Exochelin MS
      has three hydroxamic acid groups for Fe(III) chelation and has four additional
      acidic protons from a carboxylic acid group and three primary amine groups, on
      the backbone of the molecule. The pK(a) values for the three hydroxamic acid
      moieties, the carboxylic acid group and the alkylammonium groups on ExoMS,
      correspond well with the literature values for these moieties. Equilibrium
      constants for proton-dependent Fe(III)-ExoMS equilibria were determined using a
      model involving the sequential protonation of the Fe(III)-ExoMS complexes at the
      first and second coordination shells. The equilibrium constants (beta) for the
      overall formation of Fe(III)ExoMS(H(3))(2+) and Fe(II)ExoMS(H(3))(+) from
      Fe((aq))(3+) or Fe((aq))(2+) and the deprotonated hydroxamate coordinating group
      form of the siderophore, ExoMS(H(3))(-), are calculated as log beta(III) = 28.9
      and log beta(II) = 10.1. A calculated pFe value of 25.0 is very similar to that
      of other linear trihydroxamic acid siderophores, and indicates that ExoMS is
      thermodynamically capable of removing Fe(III) from transferrin. The E(1/2) for
      the Fe(III)-ExoMS/Fe(II)-ExoMS couple was determined from quasi reversible cyclic
      voltammograms at pH = 6.5 and found to be -380 mV.

PMID- 15446874
TI  - Iron(III) complexes of sterically hindered tetradentate monophenolate ligands as
      functional models for catechol 1,2-dioxygenases: the role of ligand
      stereoelectronic properties.
AB  - The iron(III) complexes of the monophenolate ligands 2-(bis(pyrid-2
      ylmethyl)aminomethyl)-4-nitrophenol [H(L1)], N,N-dimethyl-N'-(pyrid-2-ylmethyl)
      N'-(2-hydroxy-4-nitrobenzyl)ethylenediamine [H(L2)], N,N-dimethyl-N'-(6-methyl
      pyrid-2-ylmethyl)-N'-(2-hydroxy-4-nitrobenzyl)ethylenediamine [H(L3)], and N,N
      dimethyl-N'-(1-methylimidazole-2-ylmethyl)-N'-(2-hydroxy-4
      nitrobenzyl)ethylenediamine [H(L4)] have been obtained and studied as structural
      and functional models for the intradiol-cleaving catechol dioxygenase enzymes.
      The complexes [Fe(L1)Cl(2)].CH(3)CN (1), [Fe(L2)Cl(2)] (2), [Fe(L3)Cl(2)] (3),
      and [Fe(L4)Cl(2)] (4) have been characterized using absorption spectral and
      electrochemical methods. The single crystal X-ray crystal structures of 1 and 2
      have been successfully determined. Both the complexes possess a rhombically
      distorted octahedral coordination geometry for the FeN(3)OCl(2) chromophore. In
      2, the phenolate oxygen, the pyridine nitrogen, an amine nitrogen, and a chloride
      ion are located on the corners of a square plane with the nitrogen atom of a 
      NMe(2) group and the other chloride ion occupying the axial positions. In 1, also
      the equatorial plane is constituted by the phenolate oxygen, the pyridine
      nitrogen, an amine nitrogen atom, and a chloride ion; however, the axial
      positions are occupied by the second pyridine nitrogen and the second chloride
      ion. Interestingly, the Fe-O-C angle of 136.1 degrees observed for 2 is higher
      than that (128.5 degrees ) in 1; however, the Fe-O(phenolate) bond distances in
      both the complexes are the same (1.929 A). This illustrates the importance of the
      nearby sterically demanding coordinated -NMe(2) group and implies similar
      stereochemical constraints from the other ligated amino acid moieties in the 3,4
      PCD enzymes, the enzyme activity of which is traced to the difference in the
      equatorial and axial Fe-O(tyrosinate) bonds (Fe-O-C, 133 degrees, 148 degrees ).
      The nature of heterocyclic rings of the ligands and the methyl substituents on
      them regulates the electronic spectral features, Fe(III)/Fe(II) redox potentials,
      and catechol cleavage activity of the complexes. Upon interacting the complexes
      with catecholate anions, two catecholate to iron(III) charge transfer bands
      appear, and the low energy band is similar to that of catechol dioxygenase
      substrate complex. Complexes 1 and 3 fail to catalyze the oxidative intradiol
      cleavage of 3,5-di-tert-butylcatechol (H(2)DBC). However, interestingly, the
      replacement of pyridine pendant in 1 by the -NMe(2) group to obtain 2 restores
      the dioxygenase activity, which is consistent with its higher Fe-O-C bond angle.
      Remarkably, the more basic N-methylimidazole ring in 4 facilitates the rate
      determining product releasing phase of the catalytic reaction, leading to
      enhancement in reaction rate and efficient conversion (77.1%) of the substrate to
      intradiol cleavage products as well. All these observations provide support to
      the novel substrate activation mechanism proposed for the intradiol-cleavage
      pathway.

PMID- 15446875
TI  - Reaction properties of the trans-hyponitrite complex [Ru2(CO)4(mu-H)(mu
      PBu(t)2)(mu-Ph2PCH2PPh2)(mu-eta2-ONNO)].
AB  - The protonation of [Ru(2)(CO)(4)(mu-H)(mu-PBu(t)()(2))(mu-dppm)(mu-eta(2)-ONNO)]
      (1) with HBF(4) occurs at the oxygen of the noncoordinating side of the trans
      hyponitrite ligand to give [Ru(2)(CO)(4)(mu-H)(mu-PBu(t)()(2))(mu-dppm)(mu-eta(2)
      ONNOH)][BF(4)] (2) in good yield. The monoprotonated hyponitrite in 2 is
      deprotonated easily by strong bases to regenerate 1. Furthermore, 1 reacts with
      the methylating reagent [Me(3)O][BF(4)] to afford [Ru(2)(CO)(4)(mu-H)(mu
      PBu(t)()(2))(mu-dppm)(mu-eta(2)-ONNOMe)][BF(4)] (3). The molecular structures of
      2 and 3 have been determined crystallographically, and the structure of 2 is
      discussed with the results of the DFT/B3LYP calculations on the model complex
      [Ru(2)(CO)(4)(mu-H)(mu-PH(2))(mu-H(2)PCH(2)PH(2))(mu-eta(2)-ONNOH)](+) (2a).
      Moreover, the thermolysis of 2 in ethanol affords [Ru(2)(CO)(4)(mu-H)(mu-OH)(mu
      PBu(t)()(2))(mu-dppm)][BF(4)] (4) in high yield, and the deprotonation of 4 by
      DBU in THF yields the novel complex [Ru(2)(CO)(4)(mu-OH)(mu-PBu(t)()(2))(mu
      dppm)] (5).

PMID- 15446876
TI  - Unprecedented oxo-titanium citrate complex precipitated from aqueous citrate
      solutions, exhibiting a novel bilayered Ti8O10 structural core.
AB  - Aqueous titanium citrate solutions were prepared from the reaction of citric acid
      with titanium 2-propoxide in a range of molar ratios. Solutions containing two or
      fewer citrates per titanium resulted in the slow crystallization of an insoluble
      titanium oxo-citrate complex. Single-crystal X-ray analysis identified the
      species as Ti(8)O(10)(citrate)(4)(H(2)O)(12).14H(2)O.3HOPr(i)(), crystallized in
      the tetragonal space group I4(1)/a, with a = 30.775(7) A, c = 14.528(7) A, V = 13
      759(8) A(3), and Z = 8. The trianionic citrate ligands supply both carboxylate
      and alkoxide coordination and stabilize the structure using simultaneous
      chelating and bridging modes of attachment. The compound is a neutral species,
      exhibiting titanium in three contrasting environments. Laser Raman microscopy and
      (13)C CPMAS solid-state NMR data were consistent with those of the X-ray crystal
      structure. When exposed to air, the crystals rapidly lost water and became a
      powder. The dehydrated powder was noncrystalline to X-rays and insoluble, but
      (13)C NMR results demonstrated retention of the carboxylate linkages.

PMID- 15446877
TI  - Heterometallic Ln/Hg compounds with fluorinated thiolate ligands.
AB  - The early lanthanide benzenefluorothiolates (Ln(SC(6)F(5))(3); Ln = La, Ce, Pr,
      Nd, Sm, Gd) react with Hg(SC(6)F(5))(2) in DME to form ionic heterometallic
      compounds with Ln cations and Hg anions. X-ray diffraction analyses of all
      compounds reveal an isostructural series with the general formula
      [(DME)(3)Ln(SC(6)F(5))(2)](2)[Hg(2)(SC(6)F(5))(6)]. In the structures, a
      fluorothiolate ligand has been extracted from the Ln coordination sphere that is
      saturated with three neutral DME donor ligands and a dative interaction between
      one ortho fluorine and the Ln. Distances between Ln and F do not vary simply with
      Ln ionic radius. There are two Ln cations with charge balanced by a
      Hg(2)(SC(6)F(5))(6) dianion composed of two distinctly nonideal Hg(II)
      tetrahedra, all connected through a series of pi-pi interactions that link
      cations with anions in a one-dimensional array and anions to anions in a more
      complex 2D network.

PMID- 15446878
TI  - Synthesis and evaluation of a high relaxivity manganese(II)-based MRI contrast
      agent.
AB  - The manganese(II) ion has many favorable properties that lead to its potential
      use as an MRI contrast agent: high spin number, long electronic relaxation time,
      labile water exchange. The present work describes the design, synthesis, and
      evaluation of a novel Mn(II) complex (MnL1) based on EDTA and also contains a
      moiety that noncovalently binds the complex to serum albumin, the same moiety
      used in the gadolinium based contrast agent MS-325. Ultrafiltration albumin
      binding measurements (0.1 mM, pH 7.4, 37 degrees C) indicated that the complex
      binds well to plasma proteins (rabbit: 96 +/- 2% bound, human: 93 +/- 2% bound),
      and most likely to serum albumin (rabbit: 89 +/- 2% bound, human 98 +/- 2%
      bound). Observed relaxivities (+/- 5%) of the complex were measured (20 MHz, 37
      degrees C, 0.1 mM, pH 7.4) in HEPES buffer (r(1) = 5.8 mM(-)(1) s(-)(1)), rabbit
      plasma (r(1) = 51 mM(-)(1) s(-)(1)), human plasma (r(1) = 46 mM(-)(1) s(-)(1)),
      4.5% rabbit serum albumin (r(1) = 47 mM(-)(1) s(-)(1)), and 4.5% human serum
      albumin (r(1) = 48 mM(-)(1) s(-)(1)). The water exchange rate was near optimal
      for an MRI contrast agent (k(298) = 2.3 +/- 0.9 x 10(8) s(-)(1)). Variable
      temperature NMRD profiles indicated that the high relaxivity was due to slow
      tumbling of the albumin-bound complex and fast exchange of the inner sphere
      water. The concept of a high relaxivity Mn(II)-based contrast agent was validated
      by imaging at 1.5 T. In a rabbit model of carotid artery injury, MnL1 clearly
      delineated both arteries and veins while also distinguishing between healthy
      tissue and regions of vessel damage.

PMID- 15446879
TI  - Binuclear copper(II) oxidation products from copper(I) complexes with tridentate
      ligands. Magnetostructural characterization.
AB  - The bis-pyridine tridentate ligands (6-R-2-pyridylmethyl)-(2-pyridylmethyl)
      benzylamine (RDPMA, where R = CH(3), CF(3)), (6-R-2-pyridylmethyl)-(2
      pyridylethyl) benzylamine (RPMPEA, where R = CH(3), CF(3)), and the bidentate
      ligand di-benzyl-(6-methyl-2-pyridylmethyl)amine (BiBzMePMA) have been
      synthesized and their copper(I) complexes oxidized in a methanol solution to
      afford self-assembled bis-micro-methoxo-binuclear copper(II) complexes (1, 2, 4,
      6) or hydroxo- binuclear copper(II) complexes (3). Oxidation of the
      nonsubstituted DPMA (R = H) in dichloromethane gives a chloride-bridged complex
      (5). The crystal structures for [Cu(MeDPMA)(MeO)](2)(ClO(4))(2) (1),
      [Cu(RPMPEA)(MeO)](2)(ClO(4))(2) (for 2, R= Me, and for 4, R = CF(3)),
      [Cu(BiBzMePMA)(MeO)](2)(ClO(4))(2) (6), [Cu(FDPMA)(OH)](2)(ClO(4))(2) (3), and
      [Cu(DPMA)(Cl)](2)(ClO(4))(2) (5) have been determined, and their variable
      temperature magnetic susceptibility has been measured in the temperature range of
      10-300 K. The copper coordination geometries are best described as square
      pyramidal, except for 6, which is square planar, because of the lack of one
      pyridine ring in the bidentate ligand. In 1-4 and 6, the basal plane is formed by
      two pyridine N atoms and two O atoms from the bridging methoxo or hydroxo groups,
      whereas in 5, the bridging Cl atoms occupy axial-equatorial sites. Magnetic
      susceptibility measurements show that the Cu atoms are strongly coupled
      antiferromagnetically in the bis-methoxo complexes 1, 2, 4, and 6, with -2J > 600
      cm(-)(1), whereas for the hydroxo complex 3, -2J = 195 cm(-)(1) and the chloride
      bridged complex 5 shows a weak ferromagnetic coupling, with 2J = 21 cm(-)(1) (2J
      is an indicator of the magnetic interaction between the Cu centers).

PMID- 15446880
TI  - Hexacoordinate planar main group atoms centered in hexagonal hydrocopper
      complexes Cu6H6X (X = Si, P, As).
AB  - Ab initio theoretical evidence of hexacoordinate planar main group atoms centered
      in hexagonal hydrocopper complexes Cu(6)H(6)X (X = Si, P, As) is presented at the
      density functional theory level in this work. The results obtained extend the
      bonding capacity of silicon, phosphorus, and arsenic to planar hexacoordination
      in hydrocopper complexes which are important in fundamental research and may shed
      new insight into catalyst chemistry.

PMID- 15446881
TI  - Thienyl carboxylate ligands bound to and bridging MM quadruple bonds, M = Mo or
      W: models for polythiophenes incorporating MM quadruple bonds.
AB  - A series of compounds of the form [M(2)L(4)] and [[((t)()BuCO(2))(3)M(2)](2)(mu
      L')] have been made where M = Mo or W, L = a thienyl, bithienyl, or terthienyl
      carboxylate, and L' = a corresponding thienyl dicarboxylate. The electronic
      absorption spectra are reported and the electronic structures discussed. Intense
      metal-to-ligand charge transfer bands traverse the visible and near-IR regions of
      the electronic absorption spectrum. The compounds show reversible metal-based
      oxidations and quasireversible ligand-based reductions. The molecular structure
      of Mo(2)(O(2)C-2-Th)(4).2THF is reported, on the basis of a single crystal X-ray
      diffraction study. These compounds provide insight into the expected properties
      of related dimetalated polythiophenes incorporating MM quadruple bonds.

PMID- 15446882
TI  - Synthesis and crystal structure of two new discrete, neutral complexes of
      manganese and zinc using a rigid organic clip.
AB  - Two discrete neutral dimanganese(II) and tetrazinc(II) complexes were synthesized
      from a rigid organic clip and the corresponding metal acetates. The compounds
      were characterized by elemental analysis and single crystal X-ray diffraction
      study. The manganese species is a dinuclear discrete product with two disordered
      acetates bridging two manganese centers, while the zinc one consists of two
      octahedral and two tetrahedral Zn(II) centers with both bridging acetates and
      triply micro(3)-hydroxides. Variable temperature magnetic measurement reveals the
      existence of weak antiferromagnetic interaction (J = -1.6 cm(-)(1); H = 
      2JS(1).S(2)) within the manganese complex.

PMID- 15446883
TI  - Bilayers, corrugated bilayers, and coordination polymers of p
      sulfonatocalix[6]arene.
AB  - Exploration into the host-guest supramolecular chemistry of p
      sulfonatocalix[6]arene with pyridine N-oxide and 4,4'-dipyridine N,N'-dioxide has
      resulted in the characterization of three new structural motifs with the
      calixarene in the "up-down" double partial cone conformation. Two are hydrogen
      bonded network structures formed with pyridine N-oxide and either nickel or
      lanthanide metal counterions (1 and 2, respectively). Complex 1 displays host
      guest interactions between pyridine N-oxide and the calixarene in the presence of
      hexaaquanickel(II) counterions. Complex 2 demonstrates selective coordination
      modes for different lanthanides involving the calixarene and pyridine N-oxide.
      The third structure, 3, is a coordination polymer which is formed with 4,4'
      dipyridine N,N'-dioxide molecules which span a hydrophilic layer and join
      lanthanide/p-sulfonatocalix[6]arene fragments. Although complexes 1-3 all have
      the calixarene in the "up-down" double partial cone conformation, 1 and 3 form
      bilayer arrangements within the extended structures while 2 forms a previously
      unseen corrugated bilayer arrangement.

PMID- 15446884
TI  - Reactions of meso-hydroxyhemes with carbon monoxide and reducing agents in search
      of the elusive species responsible for the g = 2.006 resonance of carbon monoxide
      treated heme oxygenase. Isolation of diamagnetic iron(II) complexes of octaethyl
      meso-hydroxyporphyrin.
AB  - To examine possible models for the g = 2.006 resonance seen when the hydroxylated
      heme-heme oxygenase complex in the Fe(III) state is treated with CO, the
      reactivities of CO and reducing agents with (py)(2)Fe(III)(OEPO) and
      [Fe(III)(OEPO)](2) (OEPO is the trianion of octaethyl-meso-hydroxyporphyrin) have
      been examined. A pyridine solution of (py)(2)Fe(III)(OEPO) reacts in a matter of
      minutes with zinc amalgam (or with hydrazine) under an atmosphere of dioxygen
      free dinitrogen to produce bright-red (py)(2)Fe(II)(OEPOH).2py.0.33H(2)O, which
      has been isolated in crystalline form. The (1)H NMR spectrum of
      (py)(2)Fe(II)(OEPOH) in a pyridine-d(5) solution is indicative of the presence of
      a diamagnetic compound, and no EPR resonance was observed for this compound.
      Treatment of a solution of (py)(2)Fe(II)(OEPOH) in pyridine-d(5) with carbon
      monoxide produces spectral changes after a 30 s exposure that are indicative of
      the formation of diamagnetic (OC)(py)Fe(II)(OEPOH). Treatment of a green pyridine
      solution of (py)(2)Fe(III)(OEPO) with carbon monoxide reveals a slow color change
      to deep red over a 16 h period. Although a resonance at g = 2.006 was observed in
      the EPR spectrum of the sample during the reaction, the isolated product is EPR
      silent. The spectroscopic features of the final solution are identical to those
      of a solution formed by treating (py)(2)Fe(II)(OEPOH) with carbon monoxide.
      Addition of hydrazine to solutions of (OC)(py)Fe(II)(OEPOH) produces red,
      diamagnetic (OC)(N(2)H(4))Fe(II)(OEPOH).py in crystalline form. The X-ray crystal
      structures of (py)(2)Fe(II)(OEPOH).2py.0.33H(2)O and
      (OC)(N(2)H(4))Fe(II)(OEPOH).py have been determined. Solutions of diamagnetic
      (OC)(N(2)H(4))Fe(II)(OEPOH).py and (OC)(py)Fe(II)(OEPOH) are extremely air
      sensitive and are immediately converted in a pyridine solution into paramagnetic
      (py)(2)Fe(III)(OEPO) in the presence of dioxygen.

PMID- 15446885
TI  - Fluorescence-based nitric oxide detection by ruthenium porphyrin fluorophore
      complexes.
AB  - The ruthenium(II) porphyrin fluorophore complexes [Ru(TPP)(CO)(Ds-R)] (TPP =
      tetraphenylporphinato dianion; Ds = dansyl; R = imidazole (im), 1, or
      thiomorpholine (tm), 2) were synthesized and investigated for their ability to
      detect nitric oxide (NO) based on fluorescence. The X-ray crystal structures of 1
      and 2 were determined. The Ds-im or Ds-tm ligand coordinates to an axial site of
      the ruthenium(II) center through a nitrogen or sulfur atom, respectively. Both
      exhibit quenched fluorescence when excited at 368 or 345 nm. Displacement of the
      metal-coordinated fluorophore by NO restores fluorescence within minutes. These
      observations demonstrate fluorescence-based NO detection using ruthenium
      porphyrin fluorophore conjugates.

PMID- 15446886
TI  - Synthesis and crystal structure of lithium beryllium deuteride Li2BeD4.
AB  - Single-phase ternary deuteride Li(2)BeD(4) was synthesized by a high-pressure
      high-temperature technique from LiD and BeD(2). The crystal structure of
      Li(2)BeD(4) was solved from X-ray and neutron powder diffraction data. The
      compound crystallizes in the monoclinic space group P2(1)/c with lattice
      parameters a = 7.06228(9) A, b = 8.3378(1) A, c = 8.3465(1) A, beta =93.577(1)
      degrees, and Z = 8. Its structure contains isolated BeD(4) tetrahedra and Li
      atoms that are located in the structure interstices. Li(2)BeD(4) does not undergo
      any structural phase transitions at temperatures down to 8 K.

PMID- 15446887
TI  - Density functional study of valence trapping in a mixed-valent dimanganese
      complex.
AB  - Density functional calculations are reported for the linked system
      [(Fulv)[Mn(CO)(2)](2)(mu-dppm)] in the neutral and singly and doubly charged
      states. The neutral system and dication are characterized by well-localized
      valence states involving two Mn(II) and Mn(I) centers, respectively. At the
      BP86/AE1 level, the electronic structure of the monocation is that of a
      delocalized mixed-valence species. At the B3LYP/AE1 level, the spin density of
      the unpaired electron is largely localized on one Mn atom, in accord with the
      formulation of a trapped-valence ground state (Atwood, C. G.; Geiger, W. E. J.
      Am. Chem. Soc. 2000, 122, 5477). The qualitative IR pattern of the CO stretching
      vibrations is well reproduced at the B3LYP level, supporting the empirical charge
      distribution parameter employed for the interpretation of the IR spectra.

PMID- 15446888
TI  - Synthesis, characterization, and photochemical and computational investigations
      of Ru(II) heterocyclic complexes containing 2,6-dimethylphenylisocyanide (CNx)
      ligand.
AB  - The isocyanide ligand forms complexes with ruthenium(II) bis-bipyridine of the
      type [Ru(bpy)(2)(CNx)Cl](CF(3)SO(3)) (1), [Ru(bpy)(2)(CNx)(py)](PF(6))(2) (2),
      and [Ru(bpy)(2)(CNx)(2)](PF(6))(2) (3) (bpy = 2,2'-bipyridine, py = pyridine, and
      CNx = 2,6-dimethylphenylisocyanide). The redox potentials shift positively as the
      number of CNx ligands increases. The metal-to-ligand charge-transfer (MLCT) bands
      of the complexes are located at higher energy than 450 nm and blue shift in
      proportion to the number of CNx ligands. The complexes are not emissive at room
      temperature but exhibit intense structured emission bands at 77 K with emission
      lifetimes as high as 25 micros. Geometry optimization of the complexes in the
      singlet ground and lowest-lying triplet states performed using density functional
      theory (DFT) provides information about the orbital heritage and correlates with
      X-ray and electrochemical results. The lowest-lying triplet-state energies
      correlate well with the 77 K emission energies for the three complexes. Singlet
      excited states calculated in ethanol using time-dependent density functional
      theory (TDDFT) and the conductor-like polarizable continuum model (CPCM) provide
      information that correlates favorably with the experimental absorption spectra in
      ethanol.

PMID- 15446889
TI  - Characterization of 2,3-dihydroxyterephthalamides as M(IV) chelators.
AB  - The ligand N,N'-diethyl-2,3-dihydroxyterephthalamide (ETAM) has been
      characterized as a chelator for Zr(IV), Ce(IV), and Th(IV). The K(+) salts of the
      complexes [Zr(ETAM)(4)](4)(-), [Ce(ETAM)(4)](4)(-), and [Th(ETAM)(4)](4)(-) were
      prepared in a MeOH solution containing H(2)ETAM, the corresponding M(acac)(4),
      and 4 equiv of KOH. Single-crystal X-ray diffraction analyses are reported for
      K(4)[Zr(ETAM)(4)] (C2/c, Z = 8, a = 27.576(3) A, b = 29.345(3) A, c = 15.266(2)
      A, alpha = 90 degrees, beta = 118.688(4) degrees, gamma = 90 degrees ),
      [Me(3)BnN](4)[Th(ETAM)(4)] (P, Z = 2, a = 13.7570(3) A, b = 13.9293(3) A, c =
      26.9124(6) A, alpha = 99.941(1) degrees, beta = 94.972(1) degrees, gamma =
      103.160(1) degrees ), and the dimeric (NMe(4))(4)[Th(ETAM)(3)MeOH](2) (P2(1)/c, Z
      = 4, a = 18.2603(9) A, b = 18.5002(9) A, c = 19.675(1) A, beta = 117.298(1)
      degrees ). Solution thermodynamic studies were used to determine formation
      constants (log K(f) and esd) for Th(IV)-ETAM log K(110) =17.47(1), log K(120) =
      13.23(1), log K(130) = 8.28(3), log K(140) = 6.57(6), and log beta(140) =
      45.54(5). These results support the hypothesis that the terephthalamides are high
      affinity chelators for the actinide(IV) ions and thus promising ligands for use
      in nuclear waste remediation.

PMID- 15446890
TI  - Synthesis and characterization of the first organically templated metal
      oxalatophosphonate: (C3H12N2)0.5[Ga3(C2O4)(CH3PO3)4].0.5H2O.
AB  - The first organically templated gallium oxalatophosphonate has been synthesized
      under hydrothermal conditions and characterized by single-crystal X-ray
      diffraction, infrared spectroscopy, and thermogravimetric analysis. The structure
      consists of GaO(6) octahedra and GaO(4) tetrahedra connected by methylphosphonate
      and bis-bidentate oxalate anions to form anionic sheets in the ab plane with the
      charge-compensating propylenediammonium cations and water molecules between the
      sheets. The methyl groups of the phosphonate ligands extend from both sides of
      the layers into the interlamellar region. Crystal data: monoclinic, space group
      P2(1)/n (No. 14), a = 8.8514(4) A, b = 16.3030(7) A, c = 15.0816(7) A, beta =
      97.539(1) degrees, and Z = 4.

PMID- 15446891
TI  - Charge-transfer hybrids containing covalently bonded polyoxometalates and
      ferrocenyl units.
AB  - Two new charge-transfer hybrids with one or two ferrocenyl units covalently
      attached to a hexamolybdate cluster through an extended pi-conjugated bridge have
      been prepared using Pd-catalyzed coupling reactions on monoiodo- or diiodo
      functionalized cluster substrates in over 60% yields. These hybrids have been
      characterized by (1)H NMR, FTIR, electrospray ionization mass spectrometry, and X
      ray diffraction. The electronic spectra of these hybrids show a broad absorption
      tail extending beyond 550 nm, indicating the existence of charge-transfer
      transition from the ferrocenyl donor to the cluster acceptor. The observation of
      the clear charge-transfer transition indicates the contribution of charge
      transfer resonance to the ground state in both 2a and 2b even though the donor
      acceptor separation distance of 11.29 A is rather long, signaling a through-bond
      charge-transfer nature made possible by the organic pi-conjugated bridge. Cyclic
      voltammetry studies reveal a one-electron oxidation wave and a one-electron
      reduction wave for the hybrid with one ferrocenyl unit. For the one with two
      ferrocenyl units, a lower reduction potential and a two-electron oxidation wave
      are observed, indicating negligible electronic interactions between the two
      ferrocenyl units.

PMID- 15446892
TI  - Vanadium 7,7,8,8-tetracyano-p-quinodimethane (V[TCNQ]2)-based magnets.
AB  - A new family of molecule-based magnets of general formula
      V[TCNQR(2)](2).zCH(2)Cl(2) has been synthesized and characterized (TCNQ = 7,7,8,8
      tetracyano-p-quinodimethane; R = H, Br, Me, Et, i-Pr, OMe, OEt, and OPh). In
      addition, solid solutions of V[TCNQ](x)()[TCNQ(OEt)(2)](2)(-)(x)().zCH(2)Cl(2)
      composition have been prepared. Except R = Br, magnetic ordering was observed for
      all materials, with T(c) values between 7.5 K (R = Me) and 106 K (R = OEt), with
      R = H at 52 K. The substitution of electron-donating OMe and OEt groups for H in
      TCNQ increased T(c), whereas the substitution of less electron-donating alkyl
      groups (with respect to alkoxy groups) decreased T(c). The results of MO
      calculations indicate that neither the spin nor charge densities of the
      disubstituted TCNQs are sufficiently different to explain the wide range of
      critical temperatures. Although the structures of the amorphous materials are not
      known, it is proposed that the oxygen atom of the [TCNQR(2)](*)(-) acceptor (R =
      OMe and OEt) and the V(II) interact to form a seven-membered ring. This
      interaction could stabilize the structure and enhance the magnetic coupling,
      leading to an increased T(c). The magnetic properties of
      V[TCNQ](x)()[TCNQ(OEt)(2)](2)(-)(x)().zCH(2)Cl(2) deviated from the expected
      linear relationship with respect to x, exhibiting magnetic behavior more
      characteristic of a step function in a plot of T(c) versus x.

PMID- 15446893
TI  - Insertion of iodine in a functionalized inorganic layered solid.
AB  - The galleries of a Mg-Al layered double hydroxide have been functionalized by
      intercalation of (carboxymethyl)-beta-cyclodextrin cavities. The functionalized
      inorganic solid can adsorb iodine molecules from vapor as well as nonaqueous and
      aqueous solutions. The adsorbed iodine complexes with the grafted cyclodextrin
      cavities, disassociating heterolytically to form polyiodide species. Electronic
      and Raman spectra provide conclusive evidence for the existence of linear
      symmetric triodide, I(3)(-), and pentaiodide, I(5)(-), species within the
      cyclodextrin cavities confined in the layered double hydroxide.

PMID- 15446894
TI  - The role of neutral coligands on the stabilization of mono-Tp(i)Pr2 U(III)
      complexes.
AB  - The reaction of [UI(3)(THF)(4)] with 1 equiv of KTp()i(Pr)()2 in toluene in the
      presence of several neutral coligands allowed the synthesis of a novel family of
      mono-Tp()i(Pr)()2 complexes, [UI(2)Tp()i(Pr)()2(L)(x)()] [L = OPPh(3), x = 1 (3);
      L = C(5)H(5)N, x = 2 (4); L = Hpz()t(Bu,Me), x = 2 (5); and L = bipy, x = 1 (6)].
      The adduct with THF, [UI(2)Tp()i(Pr)()2(THF)(2)(-)(3)] (1), could also be
      isolated by reacting [UI(3)(THF)(4)] with 1 equiv of KTp()i(Pr)()2 in
      tetrahydrofuran. However, complex 1 is not a good starting material to enter into
      the mono-Tp()i(Pr)()2 U(III) complexes as it decomposes in solution, leading to
      mixtures of U(III) species coordinated with Hpz()i(Pr)()2. The solid-state
      structures of 3, 4, and 6 were determined by single-crystal X-ray diffraction and
      revealed that this family of mono-Tp()i(Pr)()2 complexes can be six- (3) or seven
      coordinated (4 and 6), depending on the nature of the neutral coligand. Complex 3
      displays distorted octahedral coordination geometry, while 4 and 6 display
      distorted pentagonal bipyramid and capped octahedral geometries, respectively.
      Complexes 3 and 6 are static in solution, and the patterns of the (1)H NMR
      spectra are consistent with the C(s)() symmetry found in the solid state. The
      other complexes (1, 4, and 5) are fluxional, but the dynamic processes involved
      can be slowed by decreasing the temperature.

PMID- 15446895
TI  - Cobalt(III) complexes of monodentate N9-bound adeninate (ade-), [Co(ade
      kappaN9)Cl(en)2]+ (en = 1,2-diaminoethane): syntheses, crystal structures, and
      protonation behaviors of the geometrical isomers.
AB  - In acidic aqueous solution, a cobalt(III) complex containing monodentate N(9)
      bound adeninate (ade(-)), cis-[Co(ade-kappaN(9))Cl(en)(2)]Cl (cis-[1]Cl),
      underwent protonation to the adeninate moiety without geometrical isomerization
      or decomposition of the Co(III) coordination sphere, and complexes of cis
      [CoCl(Hade)(en)(2)]Cl(2) (cis-[2]Cl(2)) and cis-[Co(H(2)ade)Cl(en)(2)]Cl(3) (cis
      [3]Cl(3)) could be isolated. The pK(a) values of the Hade and H(2)ade(+)
      complexes are 6.03(1) and 2.53(12), respectively, at 20 degrees C in 0.1 M
      aqueous NaCl. The single-crystal X-ray analyses of cis-[2]Cl(2).0.5H(2)O and cis
      [3]Cl(2)(BF(4)).H(2)O revealed that protonation took place first at the adeninate
      N(7) and then at the N(1) atoms to form adenine tautomer (7H-Hade-kappaN(9)) and
      cationic adeninium (1H,7H-H(2)ade(+)-kappaN(9)) complexes, respectively. On the
      other hand, addition of NaOH to an aqueous solution of cis-[1]Cl afforded a
      mixture of geometrical isomers of the hydroxo-adeninato complex, cis- and trans
      [Co(ade-kappaN(9))(OH)(en)(2)](+). The trans-isomer of chloro-adeninato complex
      trans-[Co(ade-kappaN(9))Cl(en)(2)]BF(4) (trans-[1]BF(4)) was synthesized by a
      reaction of cis-[2](BF(4))(2) and sodium methoxide in methanol. This isomer in
      acidic aqueous solution was also stable toward isomerization, affording the
      corresponding adenine tautomer and adeninium complexes (pK(a) = 5.21(1) and
      2.48(9), respectively, at 20 degrees C in 0.1 M aqueous NaCl). The protonated
      product of trans-[Co(7H-Hade-kappaN(9))Cl(en)(2)](BF(4))(2).H(2)O (trans
      [2](BF(4))(2).H(2)O) could also be characterized by X-ray analysis. Furthermore,
      the hydrogen-bonding interactions of the adeninate/adenine tautomer complexes cis
      [1]BF(4), cis-[2](BF(4))(2), and trans-[2](BF(4))(2) with 1-cyclohexyluracil in
      acetonitrile-d(3) were investigated by (1)H NMR spectroscopy. The crystal
      structure of trans-[Co(ade)(H(2)O)(en)(2)]HPO(4).3H(2)O, which was obtained by a
      reaction of trans-[Co(ade)(OH)(en)(2)]BF(4) and NaH(2)PO(4), was also determined.

PMID- 15446896
TI  - Unusual reactivity of the [Re(V)O]3+ core: syntheses and characterization of
      novel rhenium halide complexes with n-methyl-o-diaminobenzene.
AB  - The reactions of 1 or 2 equiv of N-methyl-o-diaminobenzene with trans
      [ReOX(3)(PPh(3))(2)] (X = Cl, Br) in refluxing chloroform gave oxo-free rhenium
      complexes [Re(VI)X(4)(NC(6)H(4)NHCH(3))(OPPh(3))] (X = Cl, 3; X = Br, 6),
      [Re(V)X(2)Y(NC(6)H(4)NHCH(3))(PPh(3))(2)] (X, Y = Cl, 4; X = Br, Y = Cl, 7),
      [Re(IV)Cl(2)(NHC(6)H(4)NCH(3))(2)] (5), and
      [Re(IV)Br(3)(NHC(6)H(4)NCH(3))(PPh(3))] (8). All complexes were characterized by
      elemental analysis, (1)H NMR and IR spectroscopy, cyclic voltammetry, EPR
      spectroscopy, and X-ray crystallography. The complexes all display distorted
      octahedral coordination geometry. For Re(IV) complexes 5 and 8, the ligands
      coordinate in the benzosemiquinone diimine form. In Re(VI) complexes 3 and 6 and
      the Re(V) complexes 4 and 7, the ligands coordinate in the dianionic monodentate
      imido form. The EPR spectra of Re(VI) species 3 and 6 in dichloromethane solution
      at room temperature exhibit the characteristic hyperfine pattern of six lines,
      with evidence of strong second-order effects. The IR spectra of the complexes are
      characterized by Re=N and Re-N stretching bands at ca. 1090 and 540 cm(-)(1),
      respectively. The Re(IV) and Re(V) complexes display well-resolved NMR spectra,
      while the Re(VI) complexes exhibit no observable spectra, due to paramagnetism.
      The cyclic voltammograms of complexes 3 and 6 display Re(VII)/ Re(VI) and
      Re(VI)/Re(V) processes, those of 4 and 7 exhibit Re(VI)/Re(V) and Re(V)/Re(IV)
      couples, and those of 5 and 8 are characterized by Re(V)/Re(IV) and
      Re(IV)/Re(III) processes.

PMID- 15446897
TI  - Structural characterization and electronic properties determination by high-field
      and high-frequency EPR of a series of five-coordinated Mn(II) complexes.
AB  - The isolation, structural characterization, and electronic properties of a series
      of high-spin mononuclear five-coordinated Mn(II) complexes, [Mn(terpy)(X)(2)]
      (terpy = 2, 2':6',2' '-terpyridine; X = I(-) (1), Br(-) (2), Cl(-) (3), or SCN(-)
      (4)), are reported. The X-ray structures of the complexes reveal that the
      manganese ion lies in the center of a distorted trigonal bipyramid for complexes
      1, 2, and 4, while complex 3 is better described as a distorted square pyramid.
      The electronic properties of 1-4 were investigated by high-field and high
      frequency EPR spectroscopy (HF-EPR) performed between 5 and 30 K. The powder HF
      EPR spectra have been recorded in high-field-limit conditions (95-285 GHz) (D <<
      gbetaB). The spectra are thus simplified, allowing an easy interpretation of the
      experimental data and an accurate determination of the spin Hamiltonian
      parameters. The magnitude of D varies between 0.26 and 1.00 cm(-)(1) with the
      nature of the anionic ligand. Thanks to low-temperature EPR experiments, the sign
      of D was unambiguously determined. D is positive for the iodo and bromo complexes
      and negative for the chloro and thiocyano ones. A structural correlation is
      proposed. Each complex is characterized by a significant rhombicity with E/D
      values between 0.17 and 0.29, reflecting the distorted geometry observed around
      the manganese. Finally, we compared the spin Hamiltonian parameters of our five
      coordinated complexes and those previously reported for other analogous series of
      dihalo four- and six-coordinated complexes. The effect of the coordination number
      and of the geometry of the Mn(II) complexes on the spin Hamiltonian parameters is
      discussed.

PMID- 15446898
TI  - Neutral paddlewheel diruthenium complexes with tetracarboxylates of large pi
      conjugated substituents: facile one-pot synthesis, crystal structures, and
      electrochemical studies.
AB  - A one-pot reaction of a cationic diruthenium complex,
      [Ru(2)(II,III)(O(2)CCH(3))(4)(THF)(2)](BF(4)), with arylcarboxylic acids,
      ArCO(2)H, (PhCO(2)H = benzoic acid, NapCO(2)H = 1-naphthoic acid, AntCO(2)H = 9
      anthracenecarboxylic acid) in NDMA (NDMA = N,N-dimethylaniline) has led to
      isolation of neutral paddlewheel-type diruthenium complexes,
      [Ru(II)(2)(O(2)CAr)(4)(THF)(2)] (Ar = Ph (1), Nap (2), Ant (3)). Paramagnetic
      variable temperature (VT) (1)H NMR studies and GC-MS studies show that the
      reaction consists of two steps: a one-electron reduction of the Ru(2) core by
      NDMA and a simple carboxylate-exchange reaction. All compounds 1-3 were
      structurally characterized by X-ray crystallography. While the structural
      features of the Ru(2) core are very similar in all the compounds, the dihedral
      angles between the carboxylate plane and the aromatic ring are larger with the
      expanding of aryl groups from phenyl to anthracene. The effect of pi-pi stacking
      leads to the formation of a 1-D chain structure in compound 3, whereas compounds
      1 and 2 are fully isolated from each other. The electrochemical measurements show
      that the quasireversible one-electron oxidation step is observed at +0.06, +0.09,
      and +0.17 V (vs Ag/Ag(+)) for 1-3, respectively, assigned to the
      Ru(II)(2)/Ru(II,III)(2) redox couple. These potentials are found to demonstrate a
      linear relationship with the substituent constants for aryl compounds,.

PMID- 15446899
TI  - Crystal structure and physical properties of a new CuTi2S4 modification in
      comparison to the thiospinel.
AB  - A new modification of CuTi(2)S(4) was prepared from the elements at 425 degrees
      C. It crystallizes in the rhombohedral space group Rm, with lattice parameters of
      a = 7.0242(4) A, c = 34.834(4) A, and V = 1488.4(2) A(3) (Z = 12). Two
      topologically different interlayer regions exist between the close-packed S
      layers that alternate along the c axis: one comprises both Cu (in tetrahedral
      voids) and Ti atoms (in octahedral voids), and the second exclusively Ti atoms
      (again in octahedral voids). In contrast to the known modification, the spinel,
      Cu-Ti interactions of 2.88 A occur that have bonding character according to the
      electronic structure calculations. Both CuTi(2)S(4) modifications are metallic
      Pauli paramagnets due to Ti d contributions. The Pauli susceptibility of the Rm
      form is larger than that of the thiospinel in quantitative agreement with the
      LMTO-ASA band structure calculations. The irreversible transformation to the
      spinel takes place at temperatures above 450 degrees C.

PMID- 15446901
TI  - Heavy-metal aromatic rings: cyclopentadienyl anion analogues Sn5(6-) and Pb5(6-)
      in the Zintl Phases Na8BaPb6, Na8BaSn6, and Na8EuSn6.
AB  - The title compounds were prepared by direct reactions of the corresponding
      elements at high temperature. They are isostructural with each other (monoclinic,
      P2(1)/m, Z = 2; Na(8)BaPb(6), a = 13.116(4), b = 5.351(1), and c = 16.166(5) A,
      beta = 108.07(2) degrees; Na(8)BaSn(6), a = 12.897(4), b = 5.362(1), and c =
      16.826(5) A, beta = 108.19(2) degrees; Na(8)EuSn(6), a = 12.912(2), b = 5.220(1),
      and c = 15.721(2) A, beta = 108.09(1) degrees ) and contain isolated, flat, and
      aromatic pentagonal rings of Sn(5)(6)(-) and Pb(5)(6)(-) as well as isolated
      anions of Sn(4)(-) and Pb(4)(-). According to four-probe conductivity
      measurements, the tin compounds, Na(8)BaSn(6) and Na(8)EuSn(6), are
      semiconducting with band gaps of 0.11 and 0.09 eV, respectively, and are
      therefore electronically balanced. Magnetic measurements show that Na(8)BaSn(6)
      is diamagnetic while Na(8)EuSn(6) is paramagnetic and undergoes two transitions
      at low temperatures.

PMID- 15446900
TI  - Mechanism of H2O2 dismutation catalyzed by a new catalase mimic (a non-heme
      dibenzotetraaza[14]annulene-Fe(III) complex): a density functional theory
      investigation.
AB  - The mechanism of H(2)O(2) dismutation catalyzed by the
      dibenzotetraaza[14]annulene-Fe(III) complex ([Fe(C(24)H(22)N(4)O(4))](+)) which
      was recently reported (Paschke, J.; Kirsch, M.; Korth, H. G.; de Groot, H.;
      Sustmann, R. J. Am. Chem. Soc. 2001, 123, 11099) has been investigated by density
      functional theory using the B3LYP hybrid functional. The quartet potential energy
      profile of the catalytic reaction has been explored. In the whole catalytic
      cycle, the rate-determining step is found to be the O-O bond homolytic cleavage,
      without the assistance of solvent molecules in the second coordination shell. The
      calculated free energy barrier for this step is 10.8 kcal/mol, which is in
      reasonable agreement with the experimental facts. The calculations also show that
      the hydroxyl and hydroperoxyl radicals may be generated in the reaction
      processes, but they can be efficiently quenched in strongly exothermic steps.
      This study provides a satisfactory explanation to the observed efficiency of the
      H(2)O(2) dismutation catalyzed by this complex.

PMID- 15446902
TI  - Identification, isolation, and characterization of cysteinate and thiolactate
      complexes of bismuth.
AB  - Although bismuth compounds have been used in medicine for over 200 years,
      chemical characterization of complexes involving biological molecules is minimal
      and mechanisms of bioactivity are ill-defined. The thiophilic nature of bismuth
      implicates sulfur centers as likely sites for interaction, and we have exploited
      this feature to identify, isolate, and characterize complexes of bismuth with
      thiolate-carboxylate bifunctional ligands including the amino acid l-cysteine.
      The solid-state structures of potassium dichloro(thiopropionato)bismuth (K[1d]),
      dimethylaminoethanethiolato(thiopropionato)bismuth (4), and
      dinitrato(cysteinato)bismuthphenanthroline [5(phen)] are compared with data from
      electrospray ionization mass spectrometry (ESI-MS). ESI-MS is applied to
      reactions of BiCl(3) or Bi(NO(3))(3) with mercaptosuccinic, malic, and succinic
      acids to illustrate the general observation of 1:1 and 1:2 complexes.

PMID- 15446903
TI  - Tungsten(VI) complexes with aminobis(phenolato) [O,N,O] donor ligands.
AB  - The reaction between trisdiolatotungsten(VI) complex [W(eg)(3)] (1) (eg = 1,2
      ethanediolato dianion) and phenolic ligand precursor methylamino-N,N-bis(2
      methylene-4,6-dimethylphenol) (H(2)L(Me)) or methylamino-N,N-bis(2-methylene-4
      methyl-6-tert-butylphenol) (H(2)L(tBu)) affords monomeric oxotungsten complex
      [WO(eg)(L(Me))] (2) or [WO(eg)(L(tBu))] (3), respectively. These complexes react
      further with chlorinating reagents, which leads to the displacement of
      ethanediolato ligands from the complex units and formation of cis and trans
      isomers of the corresponding dichloro complexes [WOCl(2)(L(Me))] (4) and
      [WOCl(2)(L(tBu))] (5), respectively. Identical dichloro complexes were also
      prepared by the reaction between the above-mentioned phenolic ligand precursors
      and [WOCl(4)]. Molecular structures of 3, cis-4, trans-4, and cis-5 were verified
      by X-ray crystallography. Complexes 2-5 can be activated by Et(2)AlCl to catalyze
      ring-opening metathesis polymerization of norbornene.

PMID- 15446904
TI  - Signal irreproducibility in high-field solution magnetic resonance experiments
      caused by spin turbulence.
AB  - Turbulent spin dynamics arising from the joint action of radiation damping and
      the distant dipolar field are shown to generate irreproducible measurements in
      popular high-field, gradient-based magnetic resonance (MR) experiments,
      undermining the prevailing assumption of essentially predictable observables in
      MR. Sizeable fluctuations in echo amplitudes are reported and numerically
      simulated for pulsed gradient spin echo and stimulated echo diffusion
      measurements. The underlying microscopic dynamical instability is characterized
      by analysis of the finite-time Lyapunov exponents. Perturbations to the modulated
      magnetization are shown to render magic-angle gradients ineffective in
      suppressing signal fluctuations. Alternative approaches are suggested for
      cancelling out the feedback interactions leading to spin turbulence.

PMID- 15446905
TI  - State-of-the-art density matrix renormalization group and coupled cluster theory
      studies of the nitrogen binding curve.
AB  - We study the nitrogen binding curve with the density matrix renormalization group
      (DMRG) and single-reference and multireference coupled cluster (CC) theory. Our
      DMRG calculations use up to 4000 states and our single-reference CC calculations
      include up to full connected hextuple excitations. Using the DMRG, we compute an
      all-electron benchmark nitrogen binding curve, at the polarized, valence double
      zeta level (28 basis functions), with an estimated accuracy of 0.03 mEh. We also
      assess the performance of more approximate DMRG and CC theories across the
      nitrogen curve. We provide an analysis of the relative strengths and merits of
      the DMRG and CC theory under different correlation conditions.

PMID- 15446906
TI  - Quantum process tomography of the quantum Fourier transform.
AB  - The results of quantum process tomography on a three-qubit nuclear magnetic
      resonance quantum information processor are presented and shown to be consistent
      with a detailed model of the system-plus-apparatus used for the experiments. The
      quantum operation studied was the quantum Fourier transform, which is important
      in several quantum algorithms and poses a rigorous test for the precision of our
      recently developed strongly modulating control fields. The results were analyzed
      in an attempt to decompose the implementation errors into coherent (overall
      systematic), incoherent (microscopically deterministic), and decoherent
      (microscopically random) components. This analysis yielded a superoperator
      consisting of a unitary part that was strongly correlated with the theoretically
      expected unitary superoperator of the quantum Fourier transform, an overall
      attenuation consistent with decoherence, and a residual portion that was not
      completely positive-although complete positivity is required for any quantum
      operation. By comparison with the results of computer simulations, the lack of
      complete positivity was shown to be largely a consequence of the incoherent
      errors which occurred over the full quantum process tomography procedure. These
      simulations further showed that coherent, incoherent, and decoherent errors can
      often be identified by their distinctive effects on the spectrum of the overall
      superoperator. The gate fidelity of the experimentally determined superoperator
      was 0.64, while the correlation coefficient between experimentally determined
      superoperator and the simulated superoperator was 0.79; most of the discrepancies
      with the simulations could be explained by the cumulative effect of small errors
      in the single qubit gates.

PMID- 15446907
TI  - A framework model based on the Smoluchowski equation in two reaction coordinates.
AB  - The general form of the Smoluchowski equation in two reaction coordinates is
      obtained as the diffusion limit of a random walk on an infinite square grid using
      transition probabilities that satisfy detailed balance at thermodynamic
      equilibrium. The diffusion limit is then used to construct a generalization of
      the single-particle model to two reaction coordinates. The state space includes a
      square on which diffusion takes place and an isolated empty state. Boundary
      conditions on opposite sides of the square correspond to transitions between the
      empty state and the square. The two-dimensional (2D) model can be reduced to a 1D
      single-particle model by adiabatic elimination. A finite element solution of the
      2D boundary value problem is described. The method used to construct the 2D model
      can be adapted to state spaces that have been constructed by other authors to
      model K+ conduction through gramicidin, proton conduction through dioxolane
      linked gramicidin, and chloride conduction through the bacterial H(+)-Cl-
      antiporter.

PMID- 15446908
TI  - Quadratic response functions in the time-dependent four-component Hartree-Fock
      approximation.
AB  - The second-order response function has been implemented in the time-dependent
      four-component Hartree-Fock approximation. The implementation is atomic orbital
      direct and formulated in terms of Fock-type matrices. It employs a quaternion
      symmetry scheme that provides maximum computational efficiency with consideration
      made to time-reversal and spatial symmetries. Calculations are presented for the
      electric dipole first-order hyperpolarizabilities of CsAg and CsAu in the second
      harmonic generation optical process beta(-2omega;omega,omega). It is shown that
      relativistic corrections to property values are substantial in these cases--the
      orientationally averaged hyperpolarizabilities in the static limit beta(0;0,0)
      are overestimated in nonrelativistic calculations by 18% and 66% for CsAg and
      CsAu, respectively. The dispersion displays anomalies in the band gap region due
      to one- and two-photon resonances with nonrelativistically spin-forbidden states.
      Although weakly absorbing these states inflict divergences in the quadratic
      response function, since the response theoretical approach which is used adopts
      the infinite excited-state lifetime approximation. This fact calls for caution in
      applications where knowledge of the exact positioning of all excited states in
      the spectrum is unknown.

PMID- 15446909
TI  - Vibronic coupling and double excitations in linear response time-dependent
      density functional calculations: dipole-allowed states of N2.
AB  - The present study serves two purposes. First, we evaluate the ability of present
      time-dependent density functional response theory (TDDFRT) methods to deal with
      avoided crossings, i.e., vibronic coupling effects. In the second place, taking
      the vibronic coupling effects into account enables us, by comparison to the
      configuration analysis in a recent ab initio study [J. Chem. Phys. 115, 6438
      (2001)], to identify the neglect of double excitations as the prime cause of
      limited accuracy of these linear response based TDDFRT calculations for specific
      states. The "statistical averaging of (model) orbital potentials (SAOP)" Kohn
      Sham potential is used together with the standard adiabatic local-density
      approximation (ALDA) for the exchange-correlation kernel. We use the N2 molecule
      as prototype, since the TDDFRT/SAOP calculations have already been shown to be
      accurate for the vertical excitations, while this molecule has a well-studied,
      intricate vibronic structure as well as significant double excitation nature in
      the lowest 1Pi(u) state at elongated bond lengths. A simple diabatizing scheme is
      employed to obtain a diabatic potential energy matrix, from which we obtain the
      absorption spectrum of N2 including vibronic coupling effects. Considering the
      six lowest dipole allowed transitions of 1Sigma(u)+ and 1Pi(u) symmetry, we
      observe a good general agreement and conclude that avoided crossings and vibronic
      coupling can indeed be treated satisfactorily on the basis of TDDFRT excitation
      energies. However, there is one state for which the accuracy of TDDFRT/ALDA
      clearly breaks down. This is the state for which the ab initio calculations find
      significant double excitation character. To deal with double excitation character
      is an important challenge for time-dependent density functional theory.

PMID- 15446910
TI  - Fluctuation theorem and Onsager reciprocity relations.
AB  - The Onsager and higher-order reciprocity relations are derived from a fluctuation
      theorem for nonequilibrium reactions ruled by the chemical master equation. The
      fluctuation theorem is obtained for the generating function of the macroscopic
      fluxes between chemiostats maintaining the system in a nonequilibrium steady
      state. The macroscopic affinities associated with the fluxes are identified by
      graph theory. The Yamamoto-Zwanzig formulas for the reaction constants are also
      derived from the fluctuation theorem.

PMID- 15446911
TI  - Complex autocorrelation function and energy spectrum by classical trajectory
      calculations.
AB  - A quasiclassical method which enables evaluation of complex autocorrelation
      function from classical trajectory calculations is proposed. The method is
      applied for two highly excited nonlinearly coupled harmonic oscillators in
      regimes prevailed either by regular or chaotic classical motions. A good
      agreement of classical and quantum autocorrelation functions is found within
      short (Ehrnfest) time limit. Fourier transforms of the autocorrelation functions
      provide moderate resolved energy spectra, where classical and quantum results
      nearly coincide. The actual energy levels are obtained from approximate short
      time autocorrelation functions with the help of filter diagonalization. This
      study is a follow up to our previous work [P. Zdanska and N. Moiseyev, J. Chem.
      Phys. 115, 10608 (2001)], where the complex autocorrelation has been obtained up
      to overall phase factors of recurrences.

PMID- 15446912
TI  - Atomic force algorithms in density functional theory electronic-structure
      techniques based on local orbitals.
AB  - Electronic structure methods based on density-functional theory,
      pseudopotentials, and local-orbital basis sets offer a hierarchy of techniques
      for modeling complex condensed-matter systems with a wide range of precisions and
      computational speeds. We analyze the relationships between the algorithms for
      atomic forces in this hierarchy of techniques, going from empirical tight-binding
      through ab initio tight-binding to full ab initio. The analysis gives a unified
      overview of the force algorithms as applied within techniques based either on
      diagonalization or on linear-scaling approaches. The use of these force
      algorithms is illustrated by practical calculations with the CONQUEST code, in
      which different techniques in the hierarchy are applied in a concerted manner.

PMID- 15446913
TI  - An exactly solvable model for a ternary solution with three-body interactions and
      orientationally dependent bonding.
AB  - A model is considered in which the bonds of a honeycomb lattice are covered by
      rodlike molecules of types AA, BB, and AB. Neighboring molecular ends have three
      body and orientation-dependent interactions. The model is shown to be equivalent
      to a spin-1/2 Ising model on the same lattice with a field, but with only
      pairwise interactions. Symmetric and asymmetric coexistence surfaces for the
      separation into an AA-rich and a BB-rich phase are calculated exactly.

PMID- 15446914
TI  - Phase space conduits for reaction in multidimensional systems: HCN isomerization
      in three dimensions.
AB  - The three-dimensional hydrogen cyanide/isocyanide isomerization problem is taken
      as an example to present a general theory for computing the phase space
      structures which govern classical reaction dynamics in systems with an arbitrary
      (finite) number of degrees of freedom. The theory, which is algorithmic in
      nature, comprises the construction of a dividing surface of minimal flux which is
      locally a "surface of no return." The theory also allows for the computation of
      the global phase space transition pathways that trajectories must follow in order
      to react. The latter are enclosed by the stable and unstable manifolds of a so
      called normally hyperbolic invariant manifold (NHIM). A detailed description of
      the geometrical structures and the resulting constraints on reaction dynamics is
      given, with particular emphasis on the three degrees of freedom case. A procedure
      is given which uses these structures to compute orbits homoclinic to, and
      heteroclinic between, NHIMs. The role of homoclinic and heteroclinic orbits in
      global recrossings of dividing surfaces and transport in complex systems is
      explained. The complete description provided here is inherently one within phase
      space; it cannot be inferred from a configuration space picture. A
      complexification of the classical phase space structures to incorporate quantum
      effects is also discussed. The results presented here call into question certain
      assumptions routinely made on the global dynamics; this paper provides methods
      that enable one to understand and quantify the phase space dynamics of reactions
      without making such assumptions.

PMID- 15446915
TI  - Parameter space minimization methods: applications to Lennard-Jones-dipole-dipole
      clusters.
AB  - The morphology of the uniform Lennard-Jones-dipole-dipole cluster with 13 centers
      (LJDD)13 is investigated over a relatively wide range of values of the dipole
      moment. We introduce and compare several necessary modifications of the basin
      hopping algorithm for global optimization to improve its efficiency. We develop a
      general algorithm for T=0 Brownian dynamics in curved spaces, and a graph
      theoretical approach necessary for the elimination of dissociated states. We find
      that the (LJDD)13 cluster has icosahedral symmetry for small to moderate values
      of the dipole moment. As the dipole moment increases, however, its morphology
      shifts to an hexagonal antiprism, and eventually to a ring.

PMID- 15446916
TI  - Microwave investigation of the CO-CH4 van der Waals complex.
AB  - Rotational spectra of eight isotopomers of the weakly bound van der Waals complex
      CO-CH4 were recorded in the frequency range from 4 to 19 GHz using a pulsed
      molecular beam Fourier transform microwave spectrometer. For the isotopomers
      containing methane monomers of Td symmetry, namely, 12C16O-12CH4, 12C16O-13CH4,
      12C16O-12CD4, 13C16O-12CH4, and 13C18O-12CH4, three rotational progressions were
      observed that correlate to the jm=0, 1, and 2 rotational levels of free methane.
      For those containing partially deuterated methane monomers with C3V symmetry,
      namely, 12C16O-12CH3D and 12C16O-12CHD3, only two progressions were recorded,
      correlating to the jk=0(0) and 1(1) rotational levels of free CH3D and CHD3,
      respectively. The van der Waals bond distance R, intermolecular stretching
      frequency nus, and the corresponding stretching force constant ks were derived
      from the obtained spectroscopic results. The results obtained for the jm=0 ground
      state are compared to the previous infrared and millimeter wave data. A 17O
      nuclear quadrupole coupling constant was determined from the resolved hyperfine
      structure of 13C17O-12CH4 and was used to obtain angular information about the
      carbon monoxide subunit. A Coriolis interaction was deduced from the irregular
      spectral pattern involving levels with jm=1. Qualitative information about the
      extent of the perturbation was obtained from a comparison of spectroscopic
      constants of different isotopomers.

PMID- 15446917
TI  - Nonrelativistic molecular quantum mechanics without approximations: electron
      affinities of LiH and LiD.
AB  - We took the complete nonrelativistic Hamiltonians for the LiH and LiH- systems,
      as well as their deuterated isotopomers, we separated the kinetic energy of the
      center of mass motion from the Hamiltonians, and with the use of the variational
      method we optimized the ground-state nonadiabatic wave functions for the systems
      expanding them in terms of n-particle explicitly correlated Gaussian functions.
      With 3600 functions in the expansions we obtained the lowest ever ground-state
      energies of LiH, LiD, LiH-, and LiD- and these values were used to determine LiH
      and LiD electrons affinities (EAs) yielding 0.330 30 and 0.327 13 eV,
      respectively. The present are the first high-accuracy ab initio quantum
      mechanical calculations of the LiH and LiD EAs that do not assume the Born
      Oppenheimer approximation. The obtained EAs fall within the uncertainty brackets
      of the experimental results.

PMID- 15446918
TI  - Crossed beams study of the reaction 1CH2+C2H2-->C3H3+H.
AB  - The reaction of electronically excited singlet methylene (1CH2) with acetylene
      (C2H2) was studied using the method of crossed molecular beams at a mean
      collision energy of 3.0 kcal/mol. The angular and velocity distributions of the
      propargyl radical (C3H3) products were measured using single photon ionization
      (9.6 eV) at the advanced light source. The measured distributions indicate that
      the mechanism involves formation of a long-lived C3H4 complex followed by simple
      C-H bond fission producing C3H3+H. This work, which is the first crossed beams
      study of a reaction involving an electronically excited polyatomic molecule,
      demonstrates the feasibility of crossed molecular beam studies of reactions
      involving 1CH2.

PMID- 15446919
TI  - Fast hydrogen elimination from the [Ru(PH3)3(CO)(H)2] and [Ru(PH3)4(H)2]
      complexes in the first singlet excited states: a diabatic quantum dynamics study.
AB  - The photodissociation dynamics of [Ru(PH3)3(CO)(H)2] and cis-[Ru(PH3)4(H)2] is
      theoretically analyzed in the lowest two excited singlet states. Energies
      obtained through electronic density functional theory calculations that use the
      time-dependent formalism are fitted to analytical reduced two-dimensional
      potential energy surfaces (2D-PES). The metal-H2 (R) and H-H (r) distances are
      the variables of these 2D-PES, the rest of the parameters being kept frozen at
      the values of the minimum energy structure in the ground electronic state. The
      time evolution in these 2D-PES is exactly followed by means of a fast Fourier
      transform algorithm applied to solve the time-dependent Schrodinger equation. A
      simple diabatization scheme is devised to take into account the probability of
      transitions between both excited states. The quantum dynamics results point out
      that photoelimination is almost inexistent if the H2 fragment is to be expelled
      without further rearrangement of the rest of the complex. Conversely, when the
      geometries of the complex are optimized by keeping r and R frozen at the hydrogen
      elimination barrier coordinates, the new 2D-PES so obtained are highly
      dissociative, the H2 fragment being expelled in less than 100 fs. Finally the
      picture of the whole reaction that emerges from our theoretical results is
      described and the main differences between both complexes are examined.

PMID- 15446920
TI  - Vicinal fluorine-fluorine coupling constants: Fourier analysis.
AB  - Stereochemical dependences of vicinal fluorine-fluorine nuclear magnetic
      resonance coupling constants (3JFF) have been studied with the
      multiconfigurational self-consistent field in the restricted active space
      approach, with the second-order polarization propagator approximation (SOPPA),
      and with density functional theory. The SOPPA results show the best overall
      agreement with experimental couplings. The relationship with the dihedral angle
      between the coupled fluorines has been studied by Fourier analysis, the result is
      very different from that of proton-proton couplings. The Fourier coefficients do
      not resemble those of a typical Karplus equation. The four nonrelativistic
      contributions to the coupling constants of 1,2-difluoroethane configurations have
      been studied separately showing that up to six Fourier coefficients are required
      to reproduce the calculated values satisfactorily. Comparison with Fourier
      coefficients for matching hydrogen fluoride dimer configurations suggests that
      the higher order Fourier coefficients (Cn> or =3) originate mainly from through
      space Fermi contact interaction. The through-space interaction is the main reason
      3JFF do not follow the Karplus equation.

PMID- 15446921
TI  - The effect of electron detachment on the structure and properties of the chlorine
      acetonitrile anionic complex.
AB  - The results of the theoretical study of ground state potential energy surfaces
      for the chlorine-acetonitrile anion and its photodetachment product are
      presented. The shallow potential surfaces allow for the nondefinitive position of
      the chlorine within the complex. The dissociation energy of the neutral complex,
      estimated through the thermodynamic cycle, indicates significant structural
      changes due to the photodetachment process. The excess negative charge is
      localized mostly on the chlorine atom, and the electron detachment proceeds as an
      electron is removed from chlorine. The process leads to drastic changes in the
      electrostatic interactions within the complex. The first electronic excited state
      corresponds to the excess electron transfer from chlorine to acetonitrile
      fragment. This state is a precursor of the observed charge-transfer-to-solvent
      state.

PMID- 15446922
TI  - Energy levels and wave functions of weakly-bound 4Hex 20NeyH (x+y=2) systems
      using Pekeris coordinates and a symmetry-adapted Lanczos approach.
AB  - Energy levels and wave functions of floppy triatomic rare gas hydrides are
      calculated using a Pekeris coordinate system and the importance of various
      triangular configurations is assessed through the calculation of reduced
      distribution functions and relative weights. The calculations are performed using
      a symmetry-adapted Lanczos recursion within the discrete variable representation.
      For the 4He2H- anion, the present results are compared with those obtained from
      calculations based on other methods, and the accuracy of the present method is
      discussed. Calculations are also performed for the case of 4He2H and 20Ne2H, as
      well as for the mixed 4He 20NeH neutrals. Our results show that no bound states
      are found for 4He2H while only one bound state is found for both the 20Ne2H and
      4He 20NeH complexes. Interestingly, a very important and common property of these
      systems is that there is a significant contribution from linear configurations to
      their bound states.

PMID- 15446923
TI  - High-resolution spectroscopy of the 2(2)Piu<--X4Sigmag- forbidden transitions of
      C2+.
AB  - The electronic absorption spectrum of the (0,2), (1,3), and (6,9) bands of the
      B4Sigmau(-)-X4Sigmag- system of C2+ was obtained using the velocity modulation
      technique in conjunction with heterodyne detection. The rotationally resolved
      spectrum shows perturbations, which are attributed to the 2(2)Piu state. The
      mixing between the B4Sigmau- state and the 2(2)Piu state for nearly degenerate
      levels generated enough intensity borrowing to observe twenty 2(2)Piu<--X4Sigmag-
      forbidden transitions. The parameters of a model Hamiltonian were fit to the
      bands and their corresponding forbidden transitions. Line position measurements,
      line strength factors, and expectation values for the orbital angular momentum
      Lambda' for the forbidden transitions are reported. Molecular parameters from the
      global fit of each band, including their corresponding forbidden transitions, are
      reported.

PMID- 15446924
TI  - Ab initio study of the electronic spectrum of peroxyacetyl nitrate.
AB  - A theoretical study of the ground and excited states of peroxyacetyl nitrate
      (PAN), CH3C(O)OONO2, has been carried out using high level ab initio molecular
      orbital methods. The ground state geometry and vibrational frequencies are
      calculated using the coupled-cluster method. The vertical excitation energies for
      the lowest three excited states are calculated using the complete active space
      self-consistent field method along with the multireference internally contracted
      configuration interaction method. These results are compared with vertical
      excitation energies calculated with the coupled cluster equation of motion
      method. The calculation provides relevant insight into the origin of PAN
      absorption in the UV wavelength region from 200 to 300 nm. The nature of the
      electron transitions for these excited states is discussed.

PMID- 15446925
TI  - Dynamics of the F atom reaction with propene.
AB  - The F+C2H3CH3 reaction has been investigated using the crossed molecular beam
      technique. Three reaction channels have been observed in this reaction: H+C3H5F,
      CH3+C2H3F, and HF+C3H5. Time-of-flight spectra as well as product laboratory
      angular distributions have been measured for the HF, C2H3F, and C3H5F products
      from these three channels. Relative branching ratios of the three observed
      reaction channels have also been estimated. Experimental results indicate that
      these different channels exhibit significantly different reaction dynamics.

PMID- 15446926
TI  - Isotope effects and Born-Oppenheimer breakdown in excited singlet states of the
      lithium dimer.
AB  - Observation of infrared electronic transitions involving the 1 (1)Deltag state of
      7Li2 has instigated an investigation of Born-Oppenheimer breakdown in four
      singlet electronic states correlating with (2s+2s), (2s+2p), and (2p+2p) lithium
      atoms. The 1 (1)Deltag state, which correlates at long range with (2p+2p) atoms,
      has been observed in emission from the (5p) (1)Piu Rydberg state and in 1
      (1)Deltag-B (1)Piu bands, in both instances following optical-optical double
      resonance excitation. The latter transition was observed previously for the
      lighter isotopomer, 6Li2 [C. Linton, F. Martin, P. Crozet, A. J. Ross, and R.
      Bacis, J. Mol. Spectrosc. 158, 445 (1993)]. By analyzing multiple-isotopomer data
      for several electronic systems simultaneously, we have determined the electronic
      isotope shifts and the leading vibrational and/or rotational Born-Oppenheimer
      breakdown terms for the X (1)Sigmag+, A (1)Sigmau+, B (1)Piu, and 1 (1)Deltag
      states of the lithium dimer. This paper also reports Fourier transform
      measurements of the B-X absorption spectra of 6Li2 and 7Li2, which were required
      to better define the bottom portion of the B (1)Piu state potential.

PMID- 15446927
TI  - High resolution photodetachment spectroscopy of negative ions via slow
      photoelectron imaging.
AB  - A technique for high resolution anion photodetachment spectroscopy is presented
      that combines velocity map imaging and anion threshold photodetachment. This
      method, slow electron velocity-map imaging, provides spectral line widths of
      better than 1 meV. Spectra over a substantial range of electron kinetic energies
      are recorded in a single image, providing a dramatic reduction of data
      acquisition time compared to other techniques with comparable resolution. We
      apply this technique to atomic iodine and the van der Waals cluster I.CO2 as test
      systems, and then to the prereactive Cl.D2 complex where partially resolved
      structure assigned to hindered rotor motion is observed.

PMID- 15446928
TI  - Singular and nonsingular three-body integrals for exponential wave functions.
AB  - Integrals which are individually singular, but which may be combined to yield
      convergent expressions, are needed for computations of relativistic effects and
      various properties of atomic and quasiatomic systems. As computations become more
      detailed and precise, more such integrals are required. This paper presents
      general formulas for the radial parts of the singular and nonsingular (regular)
      integrals that occur when three-body systems are described using wave functions
      that include exponentials in all three interparticle coordinates. Our results are
      compared with those found in the literature for some of the integrals, and are
      also shown to be consistent with previously reported results for Hylleraas
      functions (a limiting case in which one of the exponential parameters is set to
      zero).

PMID- 15446929
TI  - Converged quantum dynamics calculations of vibrational energies of CH4 and CH3D
      using an ab initio potential.
AB  - Exact variational calculations of vibrational energies of CH4 and CH3D are
      carried out using a two-layer Lanczos algorithm based on the ab initio potential
      energy surface of D. W. Schwenke and H. Partridge, Spectrochim. Acta, Part A 57,
      887 (2001). The convergence of the calculated vibrational energies is discussed
      in detail. In addition, we report all well converged vibrational energy levels up
      to 6600 cm(-1) for CH4, and those up to 5000 cm(-1) for CH3D, respectively. These
      results clearly outperform previous theoretical calculations. And a comparison
      with experimental results available is also made.

PMID- 15446930
TI  - Real-time study of the adiabatic energy loss in an atomic collision with a metal
      cluster.
AB  - Gas-phase hydrogen atoms are accelerated towards metallic surfaces in their
      vicinity. As it approaches the surface, the velocity of an atom increases and
      this motion excites the metallic electrons, causing energy loss to the atom. This
      dissipative dynamics is frequently described as atomic motion under friction,
      where the friction coefficient is obtained from ab initio calculations assuming a
      weak interaction and slow atom. This paper tests the aforementioned approach by
      comparing to a real-time Ehrenfest molecular dynamics simulation of such a
      process. The electrons are treated realistically using standard approximations to
      time-dependent density functional theory. We find indeed that the electronic
      excitations produce a friction-like force on the atom. However, the friction
      coefficient strongly depends on the direction of the motion of the atom: it is
      large when the atom is moving towards the cluster and much smaller when the atom
      is moving away. It is concluded that a revision of the model for energy
      dissipation at metallic surfaces, at least for clusters, may be necessary.

PMID- 15446931
TI  - Quantum calculations of the O(3P)+H2-->OH+H reaction.
AB  - Quantum scattering calculations are reported for the O(3P)+H2(v=0,1) reaction
      using chemically accurate potential energy surfaces of 3A' and 3A" symmetry. We
      present state-to-state reaction cross sections and rate coefficients as well as
      thermal rate coefficients for the title reaction using accurate quantum
      calculations. Our calculations yield reaction cross sections that are in
      quantitative accord with results of recent crossed molecular beam experiments.
      Comparisons with results obtained using the J-shifting calculations show that the
      J-shifting approximation is quite reliable for this system. Thermal rate
      coefficients from the exact calculations and the J-shifting approximation agree
      remarkably well with experimental results. Our calculations also reproduce the
      markedly different OH(v'=0)/OH(v'=1) branching in O(3P)+H2(v=1) reaction,
      observed in experiments that use different O(3P) atom sources. In particular, we
      show that the branching ratio is a strong function of the kinetic energy of the
      O(3P) atom.

PMID- 15446932
TI  - Infrared spectral profiles in liquids and atom-diatom interactions.
AB  - Molecular dynamics simulations of the infrared spectrum of a generic simple polar
      diatomic in a liquid nonpolar solvent allow to reproduce the different
      prototypical experimental line shapes of this kind of systems. This is feasible
      by using different solute-solvent anisotropic potentials at fixed thermodynamic
      conditions. In the limit cases, the rotation of the diatomic is explained in
      terms of a quasifree motion or a rotational diffusion evolution and the spectra
      show a doublet structure formed by P and R branches or a unique collapsed branch,
      respectively. When the profile contains three branches, including an intense Q
      branch in the vicinity of the center of the band, rotational evolution presents a
      particular hindering that can be understood by studying the influence on
      rotational spectral densities of the different time scales involved in rotational
      relaxation. Cancellation/enhancement effects among spectral density terms arising
      from intermediate and long times (0.4-1 ps) are essential to understand
      rotational hindering.

PMID- 15446933
TI  - Single molecule kinetics. I. Theoretical analysis of indicators.
AB  - Single molecule experiments reveal intriguing phenomenon in chemical and
      biological systems. Several indicators of complex dynamics, including "intensity"
      correlations, "event" correlations, and characteristic functions have been
      proposed, but extraction of information from these indicators can be difficult
      since these indicators only observe certain characteristics of the system.
      Generally, for systems that follow Poisson kinetics, all of these indicators
      contain similar information about the relaxation times of the system and the
      connections between different relaxation times, but the information is convoluted
      in different ways so the strength of various indicators is system specific. The
      paper discusses the theoretical implications and information content of various
      data analysis methods for single molecule experiments and demonstrates the
      relationships between indicators. Under certain conditions, common indicators
      contain all available information about systems with Poisson kinetics between
      degenerate states, but extraction of this information is generally not
      numerically feasible. The paper also discusses practical issues associated with
      these analyses, which motivates a numerical study based on Bayes' formula in the
      companion paper [J. Witkoskie and J. S. Cao, J. Chem. Phys. 121, 6373 (2004),
      following paper].

PMID- 15446934
TI  - Single molecule kinetics. II. Numerical Bayesian approach.
AB  - As discussed in the companion paper [J. B. Witkoskie and J. S. Cao, J. Chem.
      Phys. 121, 6361 (2004), preceding paper], quantitative extraction of information
      from single molecule experiments by several proposed indicators is difficult
      since the experiments only observe certain characteristics of the system, even
      though the indicators can contain all available information. This paper shows how
      one can circumvent the shortcomings of these indicators by combining information
      extracted from indicators with a numerical Bayesian statistical approach. The
      Bayesian approach determines the relative probability of various models
      reproducing the entire sequence of the single molecules trajectory, instead of
      binning and averaging over the data, which removes much of this information.

PMID- 15446935
TI  - Intermolecular association in liquid N-methylacetamide as studied by x-ray
      scattering.
AB  - A structural investigation of liquid N methylacetamide was performed at 308 K
      using x-ray scattering. To extract the molecular form factor F1(q), the geometry
      of the conformer which has been found in the crystal is considered. The
      intermolecular structure function DM(q) is interpreted in terms of H-bonding
      interactions. The crystal N...O distance is taken into accounted and the number
      of H bond(s) is assumed to be, respectively, equal to one and two. The liquid
      structure can be described by a linear dimer or chainlike trimer similar to the
      ones existing in the crystal. The structure factors SM(q) extracted from these
      clusters fairly agree with the experimental one beyond q=2.5 A(-1).

PMID- 15446936
TI  - Optical control of two-photon excitation efficiency of alpha-perylene crystal by
      pulse shaping.
AB  - Optimized pulse shaping experiments were carried out on the control of two-photon
      excitation efficiency of an alpha-perylene crystal in the temperature region from
      30 to 290 K. It was found that a pulse train with a pulse interval of 90 fs and
      an alternately reversing phase relation increased the excitation efficiency by a
      factor of 2 for the whole temperature region. The pulse shape characteristic for
      effective efficiency increase was reduced by double pulse experiments in which
      the dependence of the emission intensity on the pulse interval and relative phase
      between pulses were measured. The mechanism of the efficiency increase is briefly
      discussed using a sliding-window Fourier transform of the pulse shape.

PMID- 15446937
TI  - Grand canonical Monte Carlo simulations of water in protein environments.
AB  - The grand canonical simulation algorithm is considered as a general methodology
      to sample the configuration of water molecules confined within protein
      environments. First, the probability distribution of the number of water
      molecules and their configuration in a region of interest for biochemical
      simulations, such as the active site of a protein, is derived by considering a
      finite subvolume in open equilibrium with a large system serving as a bulk
      reservoir. It is shown that the influence of the bulk reservoir can be
      represented as a many-body potential of mean force acting on the atoms located
      inside the subvolume. The grand canonical Monte Carlo (GCMC) algorithm, augmented
      by a number of technical advances to increase the acceptance of insertion
      attempts, is implemented, and tested for simple systems. In particular, the
      method is illustrated in the case of a pure water box with periodic boundary
      conditions. In addition, finite spherical systems of pure water and containing a
      dialanine peptide, are simulated with GCMC while the influence of the surrounding
      infinite bulk is incorporated using the generalized solvent boundary potential
      [W. Im, S. Berneche, and B. Roux, J. Chem. Phys. 114, 2924 (2001)]. As a last
      illustration of water confined in the interior of a protein, the hydration of the
      central cavity of the KcsA potassium channel is simulated.

PMID- 15446938
TI  - Polaron-exciton model of resonance energy transfer.
AB  - It is shown that Forster's expression for the electronic energy transfer rate can
      be recast in a form predicted for exciton motion that interacts strongly with
      molecular vibrations. Using a simple model based on the Kennard-Stepanov theory,
      Forster's expression for the spectral overlap is shown to be of a thermally
      activated form, as obtained previously by multiphonon theory. In contrast, the
      high-frequency internal vibrations contribute a factor which results from
      tunneling through a potential barrier between potential curves in the
      configuration coordinate diagram. We thus show that resonance energy transfer is
      equivalent to phonon-assisted hopping of a trapped excitonic polaron.

PMID- 15446939
TI  - The solvation structure of Pb(II) in dilute aqueous solution: an ab initio
      quantum mechanical/molecular mechanical molecular dynamics approach.
AB  - Structural properties of the hydrated Pb(II) ion have been investigated by ab
      initio quantum mechanical/molecular mechanical molecular dynamics simulations at
      Hartree-Fock quantum mechanical level. The first shell coordination number was
      found to be nine, and several other structural parameters such as angular
      distribution functions, radial distribution functions, and tilt- and theta-angle
      distributions allow the full characterization of the hydration structure of the
      Pb(II) ion.

PMID- 15446940
TI  - A centroid molecular dynamics study of liquid para-hydrogen and ortho-deuterium.
AB  - Centroid molecular dynamics (CMD) is applied to the study of collective and
      single-particle dynamics in liquid para-hydrogen at two state points and liquid
      ortho-deuterium at one state point. The CMD results are compared with the results
      of classical molecular dynamics, quantum mode coupling theory, a maximum entropy
      analytic continuation approach, pair-product forward- backward semiclassical
      dynamics, and available experimental results. The self-diffusion constants are in
      excellent agreement with the experimental measurements for all systems studied.
      Furthermore, it is shown that the method is able to adequately describe both the
      single-particle and collective dynamics of quantum liquids.

PMID- 15446941
TI  - Prediction of the thermophysical properties of pure neon, pure argon, and the
      binary mixtures neon-argon and argon-krypton by Monte Carlo simulation using ab
      initio potentials.
AB  - Gibbs ensemble Monte Carlo simulations were used to test the ability of
      intermolecular pair potentials derived ab initio from quantum mechanical
      principles, enhanced by Axilrod-Teller triple-dipole interactions, to predict the
      vapor-liquid phase equilibria of pure neon, pure argon, and the binary mixtures
      neon-argon and argon-krypton. The interaction potentials for Ne-Ne, Ar-Ar, Kr-Kr,
      and Ne-Ar were taken from literature; for Ar-Kr a different potential has been
      developed. In all cases the quantum mechanical calculations had been carried out
      with the coupled-cluster approach [CCSD(T) level of theory] and with correlation
      consistent basis sets; furthermore an extrapolation scheme had been applied to
      obtain the basis set limit of the interaction energies. The ab initio pair
      potentials as well as the thermodynamic data based on them are found to be in
      excellent agreement with experimental data; the only exception is neon. It is
      shown, however, that in this case the deviations can be quantitatively explained
      by quantum effects. The interaction potentials that have been developed permit
      quantitative predictions of high-pressure phase equilibria of noble-gas mixtures.

PMID- 15446942
TI  - Temperature dependence of density, thermal expansion coefficient and shear
      viscosity of supercooled glycerol as a reflection of its structure.
AB  - The relationship of the microstructure of supercooled, highly viscous glycerol to
      the temperature dependence of its density, thermal expansion coefficient, and
      shear viscosity are discussed. The character of this temperature dependence at
      the transition from low viscosity state to the solid amorphous state (solidified
      state without nuclei) is described with help of function psi, which can be
      interpreted as the effective number of degrees of freedom responsible for the
      change of viscosity of glycerol over a broad range; these degrees of freedom are
      those related to the alpha-relaxation process. It is shown that the change in
      effective activation energy of the viscosity is completely determined by the
      parameter psi. The change in the shear viscosity of glycerol due to the influence
      of the solid-phase nuclei is considered. It is shown that the introduction of the
      parameter phi, equal to the specific volume occupied by the nuclei of the solid
      phase, together with psi provides a natural explanation of the temperature
      dependence of density and thermal expansion coefficients of glycerol in its
      liquid, solid amorphous, glassy, and crystal states. The peculiarities of the
      temperature dependence of phi(T) and psi(T) for glycerol and o-terphenyl are
      compared.

PMID- 15446943
TI  - Transition path sampling study of classical rate-promoting vibrations.
AB  - It is now widely accepted that there is a class of enzymatic proton transfer
      reactions, which proceed through quantum tunneling. In a series of papers we have
      argued that some experimental features of these reactions can be explained by
      assuming the presence of a "rate-promoting" vibration which brings donor and
      acceptor closer together, thus leading to rate enhancement. There has never been
      a study of this effect for classical systems. We used transition path sampling to
      study the equivalent classical problem and found a complicated dynamical behavior
      that cannot be captured by transition state theory. Slow promoting vibrations
      lead to reactive trajectories that overshoot the saddle point, but on the other
      hand the short period of fast oscillations allows the reactants to stay only
      briefly in a low-barrier regime. There is a competition between these effects,
      which results to an intermediate value for the frequency of the rate-promoting
      vibration that is optimal for enhancing the rate.

PMID- 15446944
TI  - On the variation of the structure of liquid deuterium fluoride with temperature.
AB  - The structure of liquid deuterium fluoride has been measured using pulsed neutron
      diffraction and high energy x-ray diffraction techniques as a function of
      temperature. The neutron experiments were performed at T=296+/-2 K, 246+/-2 K,
      and 193+/-2 K and the x-ray measurements carried out at 296+/-2 K and 195+/-2 K.
      The x-ray pair correlation functions, which are dominated by fluorine-fluorine
      interactions, show the first peak at approximately 2.53+/-0.05 A remains very
      nearly invariant with decreasing temperature. Peaks around 4.5 and 5.0 A also
      appear at both temperatures in the x-ray data. In contrast, the intermolecular
      peaks in the total neutron pair correlation function show that significant
      systematic local structural changes occur as the temperature is lowered. The
      first intermolecular peak position shortens from 1.64+/-0.05 A at 296 K to 1.56+/
      0.05 A at 195 K. Although there are overlapping contributions from the
      intermolecular hydrogen-fluorine and hydrogen-hydrogen correlations, it is clear
      that the temperature dependent structural changes are largely due to a
      rearrangement of the deuterium atom positions in the fluid. By comparison with
      partial structure factor data the hydrogen bonds appear to become more linear at
      lower temperatures.

PMID- 15446945
TI  - Methanol-water solutions: a bi-percolating liquid mixture.
AB  - An extensive series of neutron diffraction experiments and molecular dynamics
      simulations has shown that mixtures of methanol and water exhibit extended
      structures in solution despite the components being fully miscible in all
      proportions. Of particular interest is a concentration region (methanol mole
      fraction between 0.27 and 0.54) where both methanol and water appear to form
      separate, percolating networks. This is the concentration range where many
      transport properties and thermodynamic excess functions reach extremal values.
      The observed concentration dependence of several of these material properties of
      the solution may therefore have a structural origin.

PMID- 15446946
TI  - Nonequilibrium charge recombination from the excited adiabatic state of donor
      acceptor complexes.
AB  - A model of nonequilibrium charge recombination from an excited adiabatic state of
      a donor-acceptor complex induced by the nonadiabatic interaction operator is
      considered. The decay of the excited state population prepared by a short laser
      pulse is shown to be highly nonexponential. The influence of the excitation pulse
      carrier frequency on the ultrafast charge recombination dynamics of excited donor
      acceptor complexes is explored. The charge recombination rate constant is found
      to decrease with increasing excitation frequency. The variation of the excitation
      pulse carrier frequency within the charge transfer absorption band of the complex
      can alter the effective charge recombination rate by up to a factor 2. The
      magnitude of this spectral effect decreases strongly with increasing electronic
      coupling.

PMID- 15446947
TI  - Relaxation modes in glass forming meta-toluidine.
AB  - The dynamics in supercooled meta-toluidine was studied using dielectric
      relaxation, modulated differential scanning calorimetry, proton spin-lattice
      relaxation times, and viscosity measurements. The combination of these different
      techniques has clearly shown a large decoupling of the relaxation modes whose
      origin is attributed to the formation of clusters via the NH2 bonding. This
      decoupling starts at a temperature also corresponding to a change of the
      dynamical behavior from a high temperature Arrhenius evolution to a Vogel-Fulcher
      Tamman low temperature evolution.

PMID- 15446948
TI  - Trapping of excitons at chemical defects in polyethylene.
AB  - In a previous paper we studied an injected electron-hole pair in crystalline
      polyethylene (PE) and found that the exciton becomes weakly self-trapped in a
      narrow interchain pocket comprised between two gauche defects. Despite the large
      energy stored in the trapped excitation, there did not appear to be a direct
      nonradiative channel for electron-hole recombination. Actual polyethylene systems
      of practical use are, however, neither crystalline nor pure. To understand the
      fate of an electron-hole pair in the impure case, we studied by ab initio
      simulations the evolution of an exciton trapped on three common chemical defects
      found in polyethylene: a grafted carbonyl (C=O); an intrachain vinyl group (C=C);
      a grafted carboxyl (COOH). Ab initio simulations lead to predict three different
      outcomes: trapping, nonradiative recombination, and homolitic bond-breaking,
      respectively. This suggests that extrinsic self-trapping of electron-hole pairs
      over chemical defects inside the quasicrystalline fraction of PE could be
      relevant for electrical damage in high-voltage cables.

PMID- 15446949
TI  - Theoretical investigation on electron transport through an organic molecule:
      effect of the contact structure.
AB  - Knowing how the contact geometry influences the conductance of a molecular wire
      junction requires both a precise determination of the molecule/metallic-electrode
      interface structure and an evaluation of the conductance for different contact
      geometries with a fair accuracy. With a greatly improved method to solve the
      Lippmann-Schwinger equation, we are able to include at least one atomic layer of
      each electrode into the extended molecule. The artificial effect of the jellium
      model used for the electrodes is therefore significantly reduced. Our first
      principles calculations on the transport properties of a single benzene
      dithiolate molecule sandwiched between Au(111) surfaces show that the
      transmission of the bridge site contact, which is the most stable adsorption
      configuration in equilibrium, displays different features from those of other
      configurations, and that the inclusion of the surface layers of Au electrodes
      into the extended molecule shifts and broadens the transmission peaks due to a
      stronger and more realistic S-Au bonding. We discuss the geometry dependence of
      the transport properties by analyzing the density of states of the molecular
      orbitals.

PMID- 15446950
TI  - Quantum dynamics of H2 formation on a graphite surface through the Langmuir
      Hinshelwood mechanism.
AB  - We have studied the formation of the H2 molecule on a graphite surface, when both
      H atoms are initially physisorbed. The graphite surface is assumed to be planar,
      and a model potential is obtained in a semiempirical way to reproduce the
      experimental properties of H physisorption on graphite. The reaction probability
      has been computed in the case when the angular momentum of the relative H-H
      motion lies parallel to the surface plane. Three-dimensional wave packet
      calculations have been performed for collision energies ranging from 2 to 50 meV.
      It is shown that the reaction occurs with a significant probability and produces
      the H2 molecule with a considerable amount of vibrationnal energy. A simple
      mechanical model is presented, where desorption of the nascent H2 molecule
      results from two successive binary elastic collisions.

PMID- 15446951
TI  - Melting, freezing, sublimation, and phase coexistence in sodium chloride
      nanocrystals.
AB  - Calorimetry measurements, performed by multicollision induced dissociation, have
      been used to probe the melting of a number of (NaCl)nNa+ clusters with n=22-37.
      The clusters anneal at 225-325 K and melt at 750-850 K. (NaCl)22Na+ and
      (NaCl)37Na+, which can adopt geometries that are perfect fragments of the bulk
      lattice melt at around 850 K. The other clusters, which (except for n=31) must
      have defects, melt at temperatures which are up to 100 K lower than the perfect
      nanocrystals. The internal energy distributions become bimodal near the melting
      temperature. This is the signature of slow dynamic phase coexistence where
      clusters spontaneously jump back and forth between the solid and liquid states
      with an average period that is longer than required for thermal equilibration.
      The jump frequency must be between 10(4) and 10(7) s(-1) for the bimodal
      distribution to be observable in our experiments. The (NaCl)nNa+ clusters can
      dissociate by an unusual thermally activated process where melting and freezing
      raise the internal energy to generate hot solid clusters that can sublime before
      they cool to the ambient temperature.

PMID- 15446952
TI  - Shearing of nanoscopic bridges in two-component thin liquid layers between
      chemically patterned walls.
AB  - Bridge phases associated with a phase transition between two liquid phases occur
      when a two-component liquid mixture is confined between chemically patterned
      walls. In the bulk the liquid mixture with components A, B undergoes phase
      separation into an A-rich phase and a B-rich phase. The walls bear stripes
      attractive to A. In the bridge phase A-rich and B-rich regions alternate. Grand
      canonical Monte Carlo studies are performed with the alignment between stripes on
      opposite walls varied. Misalignment of the stripes places the nanoscopic liquid
      bridges under shear strain. The bridges exert a Hookean restoring force on the
      walls for small displacements from equilibrium. As the strain increases there are
      deviations from Hooke's law. Eventually there is an abrupt yielding of the
      bridges. Molecular dynamics simulations show the bridges form or disintegrate on
      time scales which are fast compared to wall motion and transport of molecules
      into or from the confined space. Some interesting possible applications of the
      phenomena are discussed.

PMID- 15446953
TI  - Island morphology statistics and growth mechanism for oxidation of the Al(111)
      surface with thermal O2 and NO.
AB  - Scanning tunneling microscopy (STM) was employed to study the mechanism for the
      oxidation of Al(111) with thermal O2 and NO in the 20%-40% monolayer coverage
      regime. Experiments show that the islands formed upon exposure to thermal O2 and
      NO have dramatically different shapes, which are ultimately dictated by the
      dynamics of the gas surface interaction. The circumference-to-area ratio and
      other island morphology statistics are used to quantify the average difference in
      the two island types. Ultrahigh-vacuum STM was employed to make the following
      observations: (1) Oxygen islands on the Al(111) surface, formed upon exposure to
      thermal oxygen, are elongated and noncompact. (2) Mixed O/N islands on the
      Al(111) surface, formed upon exposure to thermal nitric oxide (NO), are round and
      compact. (3) STM movies acquired during thermal O2 exposure indicate that a
      complex mechanism involving chemisorption initiated rearrangement of preexisting
      oxygen islands leads to the asymmetric and elongated island shapes. The overall
      mechanism for the oxidation of the Al(111) surface can be summarized in three
      regimes. Low coverage is dominated by widely isolated small oxygen features (<3 O
      atoms) where normal dissociative chemisorption and oxygen abstraction mechanisms
      are present. At 20%-40% monolayer coverage, additional oxygen chemisorption
      induces rearrangement of preexisting islands to form free-energy minimum island
      shapes. At greater than approximately 40% monolayer coverage, the apparent
      surface oxygen coverage asymptotes corresponding to the conversion of the 2D
      islands to 3D Al2O3 surface crystallites. The rearrangement of oxygen islands on
      the surface to form the observed islands indicates that there is a short-range
      oxygen-oxygen attractive potential and a long-range oxygen-oxygen repulsive
      potential.

PMID- 15446954
TI  - Optimized Baxter model of protein solutions: electrostatics versus adhesion.
AB  - A theory is set up of spherical proteins interacting by screened electrostatics
      and constant adhesion, in which the effective adhesion parameter is optimized by
      a variational principle for the free energy. An analytical approach to the second
      virial coefficient is first outlined by balancing the repulsive electrostatics
      against part of the bare adhesion. A theory similar in spirit is developed at
      nonzero concentrations by assuming an appropriate Baxter model as the reference
      state. The first-order term in a functional expansion of the free energy is set
      equal to zero which determines the effective adhesion as a function of salt and
      protein concentrations. The resulting theory is shown to have fairly good
      predictive power for the ionic-strength dependence of both the second virial
      coefficient and the osmotic pressure or compressibility of lysozyme up to about
      0.2 volume fraction.

PMID- 15446955
TI  - Dissipative particle dynamics simulations of polymer melts. I. Building potential
      of mean force for polyethylene and cis-polybutadiene.
AB  - We present the derivation of coarse-grained force fields for two types of
      polymers, polyethylene (PE), and cis-polybutadiene (cis-PB), using the concept of
      potential of mean force. Coarse-grained force fields were obtained from
      microscopic simulations for several coarse-graining levels, i.e., different
      number of monomers lambda per mesoscopic unit called "bead." These force fields
      are then used in dissipative particle dynamics (DPD) simulations to study
      structural and dynamical properties of polymer melts of PE and cis-PB. The radial
      distribution functions g(R), the end-to-end distance R0, the end-to-end vector
      relaxation time tau, and the chain center of mass self-diffusion D(CM), are
      computed for different chain lengths at different coarse-graining factor lambda.
      Scaling laws typical of the Rouse regime are obtained for both polymers for chain
      lengths ranging from 6 to 50 beads. It is found that the end-to-end distance R0
      obtained from DPD simulations agree well with values obtained from both
      microscopic simulations and experiments. The dependence of the friction
      coefficient used in DPD simulations versus the coarse-graining level is discussed
      in view of the overall scaling of the dynamical properties.

PMID- 15446956
TI  - Exclusion zone of convex brushes in the strong-stretching limit.
AB  - We investigate asymptotic properties of long polymers grafted to convex
      cylindrical and spherical surfaces, and, in particular, distribution of chain
      free ends. The parabolic potential profile, predicted for flat and concave
      brushes, fails in convex brushes, and chain free ends span only a finite fraction
      of the brush thickness. In this paper, we extend the self-consistent model
      developed by Ball, Marko, Milner, and Witten [Macromolecules 24, 693 (1991)] to
      determine the size of the exclusion zone, i.e., size of the region of the brush
      free from chain ends. We show that in the limit of strong stretching, the brush
      can be described by an alternative system of integral equations. This system can
      be solved exactly in the limit of weakly curved brushes, and numerically for the
      intermediate to strong curvatures. We find that going from melt state to theta
      solvent and then to marginal solvent decreases relative size of the exclusion
      zone. These relative differences grow exponentially as the curvature decreases to
      zero.

PMID- 15446957
TI  - A simple theory of the interaction between polymer brushes immersed in a
      supercritical fluid.
AB  - We use a simple two-order parameter model to describe the interaction between the
      brushes of polymers terminally attached to flat surfaces immersed in a
      supercritical solvent. Our approach makes it possible to take into account the
      high compressibility of the supercritical solvent, which proves to give a
      significant contribution to the disjoining force acting between polymer brushes.
      Our theory explains why the interaction between brushes can change from repulsive
      to attractive with decreasing solvent density. This theoretical finding is
      verified by making a comparison with recent computer simulations. A reasonably
      good agreement between the results of the present theory and the simulations is
      found.

PMID- 15446958
TI  - Effects of the bead-bead potential on the restricted rotational diffusion of
      nonrigid macromolecules.
AB  - The influence of the bead-bead interaction on the rotational dynamics of
      macromolecules which are immersed into a solution has been investigated by
      starting from the microscopic theory of the macromolecular motion, i.e., from a
      Fokker-Planck equation for the phase-space distribution function. From this
      equation, we then derived an explicit expression for the configuration-space
      distribution function of a nonrigid molecule which is immobilized on a surface.
      This function contains all the information about the interaction among the beads
      as well as the effects from the surrounding solvent particles and from the
      surface. For the restricted rotational motion, the dynamics of the macromolecules
      can now be characterized in terms of a rotational diffusion coefficient as well
      as a radial distribution functions. Detailed computations for the rotational
      diffusion coefficient and the distribution functions have been carried out for
      HOOKEAN, finitely extensible nonlinear elastic, and a DNA type bead-bead
      interaction.

PMID- 15446959
TI  - Comment on "Probing the sulfur polymerization transition in situ with Raman
      spectroscopy" [J. Chem. Phys. 118, 8460 (2003)].

PMID- 15446961
TI  - Random dynamics of the Morris-Lecar neural model.
AB  - Determining the response characteristics of neurons to fluctuating noise-like
      inputs similar to realistic stimuli is essential for understanding neuronal
      coding. This study addresses this issue by providing a random dynamical system
      analysis of the Morris-Lecar neural model driven by a white Gaussian noise
      current. Depending on parameter selections, the deterministic Morris-Lecar model
      can be considered as a canonical prototype for widely encountered classes of
      neuronal membranes, referred to as class I and class II membranes. In both the
      transitions from excitable to oscillating regimes are associated with different
      bifurcation scenarios. This work examines how random perturbations affect these
      two bifurcation scenarios. It is first numerically shown that the Morris-Lecar
      model driven by white Gaussian noise current tends to have a unique stationary
      distribution in the phase space. Numerical evaluations also reveal quantitative
      and qualitative changes in this distribution in the vicinity of the bifurcations
      of the deterministic system. However, these changes notwithstanding, our
      numerical simulations show that the Lyapunov exponents of the system remain
      negative in these parameter regions, indicating that no dynamical stochastic
      bifurcations take place. Moreover, our numerical simulations confirm that,
      regardless of the asymptotic dynamics of the deterministic system, the random
      Morris-Lecar model stabilizes at a unique stationary stochastic process. In terms
      of random dynamical system theory, our analysis shows that additive noise
      destroys the above-mentioned bifurcation sequences that characterize class I and
      class II regimes in the Morris-Lecar model. The interpretation of this result in
      terms of neuronal coding is that, despite the differences in the deterministic
      dynamics of class I and class II membranes, their responses to noise-like stimuli
      present a reliable feature.

PMID- 15446962
TI  - The strange eigenmode in Lagrangian coordinates.
AB  - For a distribution advected by a simple chaotic map with diffusion, the "strange
      eigenmode" is investigated from the Lagrangian (material) viewpoint and compared
      to its Eulerian (spatial) counterpart. The eigenmode embodies the balance between
      diffusion and exponential stretching by a chaotic flow. It is not strictly an
      eigenmode in Lagrangian coordinates, because its spectrum is rescaled
      exponentially rapidly.

PMID- 15446963
TI  - Synchronizing strict-feedback chaotic system via a scalar driving signal.
AB  - We propose a systematic design procedure to synchronize a class of chaotic system
      in a so-called strict-feedback form based on back-stepping procedure. This
      approach needs only a scalar driving signal to realize synchronization no matter
      how many dimensions the chaotic system contains. Furthermore, the numerical
      simulation with Chua's chaotic circuit verifies the effectiveness of the method.

PMID- 15446964
TI  - Analysis of chaotic saddles in high-dimensional dynamical systems: the Kuramoto
      Sivashinsky equation.
AB  - This paper presents a methodology to study the role played by nonattracting
      chaotic sets called chaotic saddles in chaotic transitions of high-dimensional
      dynamical systems. Our methodology is applied to the Kuramoto-Sivashinsky
      equation, a reaction-diffusion partial differential equation. The paper describes
      a novel technique that uses the stable manifold of a chaotic saddle to
      characterize the homoclinic tangency responsible for an interior crisis, a
      chaotic transition that results in the enlargement of a chaotic attractor. The
      numerical techniques explained here are important to improve the understanding of
      the connection between low-dimensional chaotic systems and spatiotemporal systems
      which exhibit temporal chaos and spatial coherence.

PMID- 15446965
TI  - On the bound of the Lyapunov exponents for continuous systems.
AB  - In this paper, both upper bounds and lower bounds for all the Lyapunov exponents
      of continuous differential systems are determined. Several examples are given to
      show the application of the estimates derived here.

PMID- 15446966
TI  - Hydrodynamics of bacterial colonies: phase diagrams.
AB  - We present numerical simulations of a recent hydrodynamic model describing the
      growth of bacterial colonies on agar plates. We show that this model is able to
      qualitatively reproduce experimentally observed phase diagrams, which relate a
      colony shape to the initial quantity of nutrients on the plate and the initial
      wetness of the agar. We also discuss the principal features resulting from the
      interplay between hydrodynamic motions and colony growth, as described by our
      model.

PMID- 15446967
TI  - Cycling chaotic attractors in two models for dynamics with invariant subspaces.
AB  - Nonergodic attractors can robustly appear in symmetric systems as structurally
      stable cycles between saddle-type invariant sets. These saddles may be chaotic
      giving rise to "cycling chaos." The robustness of such attractors appears by
      virtue of the fact that the connections are robust within some invariant
      subspace. We consider two previously studied examples and examine these in detail
      for a number of effects: (i) presence of internal symmetries within the chaotic
      saddles, (ii) phase-resetting, where only a limited set of connecting
      trajectories between saddles are possible, and (iii) multistability of periodic
      orbits near bifurcation to cycling attractors. The first model consists of three
      cyclically coupled Lorenz equations and was investigated first by Dellnitz et al.
      [Int. J. Bifurcation Chaos Appl. Sci. Eng. 5, 1243-1247 (1995)]. We show that one
      can find a "false phase-resetting" effect here due to the presence of a skew
      product structure for the dynamics in an invariant subspace; we verify this by
      considering a more general bi-directional coupling. The presence of internal
      symmetries of the chaotic saddles means that the set of connections can never be
      clean in this system, that is, there will always be transversely repelling orbits
      within the saddles that are transversely attracting on average. Nonetheless we
      argue that "anomalous connections" are rare. The second model we consider is an
      approximate return mapping near the stable manifold of a saddle in a cycling
      attractor from a magnetoconvection problem previously investigated by two of the
      authors. Near resonance, we show that the model genuinely is phase-resetting, and
      there are indeed stable periodic orbits of arbitrarily long period close to
      resonance, as previously conjectured. We examine the set of nearby periodic
      orbits in both parameter and phase space and show that their structure appears to
      be much more complicated than previously suspected. In particular, the basins of
      attraction of the periodic orbits appear to be pseudo-riddled in the terminology
      of Lai [Physica D 150, 1-13 (2001)].

PMID- 15446968
TI  - Adaptation through minimization of the phase lag in coupled nonidentical systems.
AB  - We show that the internal control of adaptation can be obtained from the
      properties of the phase lag that results from phase synchronization of two
      nonidentical chaotic oscillators. The direction and magnitude of the phase lag
      depend upon the relative internal properties of the coupled units, and they can
      be used as indicators during the adjustment of dynamics, i.e., adaptation of the
      target unit to match that of the control. The properties of the phase lag are
      obtained using a method based on the estimation of properties of the
      distributions of relative event times of both (target and control) units. The
      phase lag dependent mechanism to control the adaptation process was applied to a
      system of nonidentical Rossler oscillators and a system of nonidentical Lorenz
      oscillators. We also elucidate its importance as a control mechanism of the
      changes of neuronal activity showing its application to neural adaptation.

PMID- 15446969
TI  - On nonlinear stability of the regular vortex systems on a sphere.
AB  - We present the necessary and sufficient conditions for stability and instability
      of the stationary rotation of a system of n identical point vortices located at
      the same latitude on a sphere at vertices of a regular n-gon. We also examine
      stability of the equilibrium configuration of identical point vortices, situated
      at the vertices of a regular polyhedra. It is proved that vortex tetrahedron,
      octahedron, and icosahedron are stable, while vortex cube and dodecahedron are
      unstable.

PMID- 15446970
TI  - An approach to chaotic synchronization.
AB  - This paper deals with the chaotic oscillator synchronization. An approach to the
      synchronization of chaotic oscillators has been proposed. This approach is based
      on the analysis of different time scales in the time series generated by the
      coupled chaotic oscillators. It has been shown that complete synchronization,
      phase synchronization, lag synchronization, and generalized synchronization are
      the particular cases of the synchronized behavior called "time-scale
      synchronization." The quantitative measure of chaotic oscillator synchronous
      behavior has been proposed. This approach has been applied for the coupled
      Rossler systems and two coupled Chua's circuits.

PMID- 15446971
TI  - Dynamic control and information processing in chemical reaction systems by tuning
      self-organization behavior.
AB  - Specific external control of chemical reaction systems and both dynamic control
      and signal processing as central functions in biochemical reaction systems are
      important issues of modern nonlinear science. For example nonlinear input-output
      behavior and its regulation are crucial for the maintainance of the life process
      that requires extensive communication between cells and their environment. An
      important question is how the dynamical behavior of biochemical systems is
      controlled and how they process information transmitted by incoming signals. But
      also from a general point of view external forcing of complex chemical reaction
      processes is important in many application areas ranging from chemical
      engineering to biomedicine. In order to study such control issues numerically,
      here, we choose a well characterized chemical system, the CO oxidation on
      Pt(110), which is interesting per se as an externally forced chemical oscillator
      model. We show numerically that tuning of temporal self-organization by input
      signals in this simple nonlinear chemical reaction exhibiting oscillatory
      behavior can in principle be exploited for both specific external control of
      dynamical system behavior and processing of complex information.

PMID- 15446972
TI  - A new spatiotemporally chaotic cryptosystem and its security and performance
      analyses.
AB  - A one-way-coupled chaotic map lattice is proposed for cryptography of self
      synchronizing stream cipher. The system performs basic floating-point analytical
      computation on real numbers, incorporating auxiliarily with few simple algebraic
      operations on integer numbers. Parallel encryption (decryption) operations of
      multiple chaotic sites are conducted. It is observed that the system has high
      practical security, fast encryption (decryption) speed with software realization,
      and excellent reliability against strong channel noise, and its overall
      cryptographic properties are considerably better than both known chaotic
      cryptosystems and currently used conventional cryptosystems, including the
      advanced encryption standard.

PMID- 15446973
TI  - Controlled test for predictive power of Lyapunov exponents: their inability to
      predict epileptic seizures.
AB  - Lyapunov exponents are a set of fundamental dynamical invariants characterizing a
      system's sensitive dependence on initial conditions. For more than a decade, it
      has been claimed that the exponents computed from electroencephalogram (EEG) or
      electrocorticogram (ECoG) signals can be used for prediction of epileptic
      seizures minutes or even tens of minutes in advance. The purpose of this paper is
      to examine the predictive power of Lyapunov exponents. Three approaches are
      employed. (1) We present qualitative arguments suggesting that the Lyapunov
      exponents generally are not useful for seizure prediction. (2) We construct a two
      dimensional, nonstationary chaotic map with a parameter slowly varying in a range
      containing a crisis, and test whether this critical event can be predicted by
      monitoring the evolution of finite-time Lyapunov exponents. This can thus be
      regarded as a "control test" for the claimed predictive power of the exponents
      for seizure. We find that two major obstacles arise in this application:
      statistical fluctuations of the Lyapunov exponents due to finite time computation
      and noise from the time series. We show that increasing the amount of data in a
      moving window will not improve the exponents' detective power for characteristic
      system changes, and that the presence of small noise can ruin completely the
      predictive power of the exponents. (3) We report negative results obtained from
      ECoG signals recorded from patients with epilepsy. All these indicate firmly
      that, the use of Lyapunov exponents for seizure prediction is practically
      impossible as the brain dynamical system generating the ECoG signals is more
      complicated than low-dimensional chaotic systems, and is noisy.

PMID- 15446974
TI  - Complex dynamics of blackouts in power transmission systems.
AB  - In order to study the complex global dynamics of a series of blackouts in power
      transmission systems a dynamical model of such a system has been developed. This
      model includes a simple representation of the dynamical evolution by
      incorporating the growth of power demand, the engineering response to system
      failures, and the upgrade of generator capacity. Two types of blackouts have been
      identified, each having different dynamical properties. One type of blackout
      involves the loss of load due to transmission lines reaching their load limits
      but no line outages. The second type of blackout is associated with multiple line
      outages. The dominance of one type of blackout over the other depends on
      operational conditions and the proximity of the system to one of its two critical
      points. The model displays characteristics such as a probability distribution of
      blackout sizes with power tails similar to that observed in real blackout data
      from North America.

PMID- 15446975
TI  - Bifurcation analysis of a model of the budding yeast cell cycle.
AB  - We study the bifurcations of a set of nine nonlinear ordinary differential
      equations that describe regulation of the cyclin-dependent kinase that triggers
      DNA synthesis and mitosis in the budding yeast, Saccharomyces cerevisiae. We show
      that Clb2-dependent kinase exhibits bistability (stable steady states of high or
      low kinase activity). The transition from low to high Clb2-dependent kinase
      activity is driven by transient activation of Cln2-dependent kinase, and the
      reverse transition is driven by transient activation of the Clb2 degradation
      machinery. We show that a four-variable model retains the main features of the
      nine-variable model. In a three-variable model exhibiting birhythmicity (two
      stable oscillatory states), we explore possible effects of extrinsic fluctuations
      on cell cycle progression.

PMID- 15446976
TI  - A simple time-delay feedback anticontrol method made rigorous.
AB  - An effective method of chaotification via time-delay feedback for a simple finite
      dimensional continuous-time autonomous system is made rigorous in this paper.
      Some mathematical conditions are derived under which a nonchaotic system can be
      controlled to become chaotic, where the chaos so generated is in a rigorous
      mathematical sense of Li-Yorke in terms of the Marotto theorem. Numerical
      simulations are given to verify the theoretical analysis.

PMID- 15446977
TI  - Hyperchaos of arbitrary order generated by a single feedback circuit, and the
      emergence of chaotic walks.
AB  - It is shown that hyperchaos of order m (i.e., with m positive Lyapunov exponents)
      can be generated by a single feedback circuit in n = 2m + 1 variables. This
      feedback circuit is constructed such that, dividing phase space into hypercubes,
      it changes sign wherever the trajectory passes from one hypercube into an
      adjacent one. Letting the negative diagonal elements in the Jacobian tend to
      zero, the dynamics becomes conservative. Instead of chaotic attractors, unbounded
      chaotic walks are then generated. Here we report chaotic walks emerging from a
      continuous system rather than the well known chaotic walks present in "Lorentz
      gas" and "couple map lattices."

PMID- 15446978
TI  - Natural computation measured as a reduction of complexity.
AB  - We argue that the deeper nature of computation is to reduce the statistical
      obstruction against prediction. From this, we derive an explicit measure of
      computation for general, artificial as well as natural, systems (electronic
      circuits, neurons, mechanical devices, etc.). The applicability and usefulness of
      this concept is demonstrated using well-studied families of dynamical systems, as
      well as experimental time series from cortical neurons.

PMID- 15446979
TI  - Entropy production and thermodynamics of nonequilibrium stationary states: a
      point of view.
AB  - Entropy might be a not well defined concept if the system can undergo
      transformations involving stationary nonequilibria. It might be analogous to the
      heat content (once called "caloric") in transformations that are not isochoric
      (i.e., which involve mechanical work): it could be just a quantity that can be
      transferred or created, like heat in equilibrium. The text first reviews the
      philosophy behind a recently proposed definition of entropy production in
      nonequilibrium stationary systems. A detailed technical attempt at defining the
      entropy of a stationary states via their variational properties follows: the
      unsatisfactory aspects of the results add arguments in favor of the nonexistence
      of a function of state to be identified with entropy; at the same time new
      aspects and properties of the phase space contraction emerge.

PMID- 15446980
TI  - Human stick balancing: tuning Levy flights to improve balance control.
AB  - State-dependent, or parametric, noise is an essential component of the neural
      control mechanism for stick balancing at the fingertip. High-speed motion
      analysis in three dimensions demonstrates that the controlling movements made by
      the fingertip during stick balancing can be described by a Levy flight. The Levy
      index, alpha, is approximately 0.9; a value close to optimal for a random search.
      With increased skill, the index alpha does not change. However, the tails of the
      Levy distribution become broader. These observations suggest a Levy flight that
      is truncated by the properties of the nervous and musculoskeletal system; the
      truncation decreasing as skill level increases. Measurements of the cross
      correlation between the position of the tip of the stick and the fingertip
      demonstrate that the role of closed-loop feedback changes with increased skill.
      Moreover, estimation of the neural latencies for stick balancing show that for a
      given stick length, the latency increases with skill level. It is suggested that
      the neural control for stick balancing involves a mechanism in which brief
      intervals of consciously generated, corrective movements alternate with longer
      intervals of prediction-free control. With learning the truncation of the Levy
      flight becomes better optimized for balance control and hence the time between
      successive conscious corrections increases. These observations provide the first
      evidence that changes in a Levy flight may have functional significance for the
      nervous system. This work has implications for the control of balancing problems
      ranging from falling in the elderly to the design of two-legged robots and
      earthquake proof buildings.

PMID- 15446981
TI  - Chaotic itinerancy in the oscillator neural network without Lyapunov functions.
AB  - Chaotic itinerancy (CI), which is defined as an incessant spontaneous switching
      phenomenon among attractor ruins in deterministic dynamical systems without
      Lyapunov functions, is numerically studied in the case of an oscillator neural
      network model. The model is the pseudoinverse-matrix version of the previous
      model [S. Uchiyama and H. Fujisaka, Phys. Rev. E 65, 061912 (2002)] that was
      studied theoretically with the aid of statistical neurodynamics. It is found that
      CI in neural nets can be understood as the intermittent dynamics of weakly
      destabilized chaotic retrieval solutions.

PMID- 15446982
TI  - Evolving complex dynamics in electronic models of genetic networks.
AB  - Ordinary differential equations are often used to model the dynamics and
      interactions in genetic networks. In one particularly simple class of models, the
      model genes control the production rates of products of other genes by a logical
      function, resulting in piecewise linear differential equations. In this article,
      we construct and analyze an electronic circuit that models this class of
      piecewise linear equations. This circuit combines CMOS logic and RC circuits to
      model the logical control of the increase and decay of protein concentrations in
      genetic networks. We use these electronic networks to study the evolution of
      limit cycle dynamics. By mutating the truth tables giving the logical functions
      for these networks, we evolve the networks to obtain limit cycle oscillations of
      desired period. We also investigate the fitness landscapes of our networks to
      determine the optimal mutation rate for evolution.

PMID- 15446983
TI  - Flow field topology of transient mixing driven by buoyancy.
AB  - Transient mixing driven by buoyancy occurs through the birth of a symmetric
      Rayleigh-Taylor morphology (RTM) structure for large length scales. Beyond its
      critical bifurcation the RTM structure exhibits self-similarity and occurs on
      smaller and smaller length scales. The dynamics of the RTM structure, its
      nonlinear growth and internal collision, show that its genesis occurs from an
      explosive bifurcation which leads to the overlap of resonance regions in phase
      space. This event shows the coexistence of regular and chaotic regions in phase
      space which is corroborated with the existence of horseshoe maps. A measure of
      local chaos given by the topological entropy indicates that as the system evolves
      there is growth of uncertainty. Breakdown of the dissipative RTM structure occurs
      during the transition from explosive to catastrophic bifurcation; this event
      gives rise to annihilation of the separatrices which drives overlap of resonance
      regions. The global bifurcation of explosive and catastrophic events in phase
      space for the large length scale of the RTM structure serves as a template for
      which mixing occurs on smaller and smaller length scales.

PMID- 15446984
TI  - A perturbative analysis of modulated amplitude waves in Bose-Einstein
      condensates.
AB  - We apply Lindstedt's method and multiple scale perturbation theory to analyze
      spatio-temporal structures in nonlinear Schrodinger equations and thereby study
      the dynamics of quasi-one-dimensional Bose-Einstein condensates with mean-field
      interactions. We determine the dependence of the amplitude of modulated amplitude
      waves on their wave number. We also explore the band structure of Bose-Einstein
      condensates in detail using Hamiltonian perturbation theory and supporting
      numerical simulations.

PMID- 15446985
TI  - Algorithmic information for interval maps with an indifferent fixed point and
      infinite invariant measure.
AB  - Measuring the average information that is necessary to describe the behavior of a
      dynamical system leads to a generalization of the Kolmogorov-Sinai entropy. This
      is particularly interesting when the system has null entropy and the information
      increases less than linearly with respect to time. We consider a class of maps of
      the interval with an indifferent fixed point at the origin and an infinite
      natural invariant measure. We show that the average information that is necessary
      to describe the behavior of the orbits increases with time n approximately as
      nalpha, where alpha < 1 depends only on the asymptotic behavior of the map near
      the origin.

PMID- 15446986
TI  - Dynamics of a single ion in a perturbed Penning trap: octupolar perturbation.
AB  - Imperfections in the design or implementation of Penning traps may give rise to
      electrostatic perturbations that introduce nonlinearities in the dynamics. In
      this paper we investigate, from the point of view of classical mechanics, the
      dynamics of a single ion trapped in a Penning trap perturbed by an octupolar
      perturbation. Because of the axial symmetry of the problem, the system has two
      degrees of freedom. Hence, this model is ideal to be managed by numerical
      techniques like continuation of families of periodic orbits and Poincare surfaces
      of section. We find that, through the variation of the two parameters controlling
      the dynamics, several periodic orbits emanate from two fundamental periodic
      orbits. This process produces important changes (bifurcations) in the phase space
      structure leading to chaotic behavior.

PMID- 15446987
TI  - Introduction: pattern formation at the turn of the millennium.

PMID- 15446988
TI  - On the back-firing instability.
AB  - The onset of the back-firing instability is studied in a one-dimensional
      spatially extended and dissipative system, where propagating localized solutions
      become unstable. It corresponds to the emission in the tail of a solitary wave of
      a new wave propagating in the opposite direction. The transition is illustrated,
      in geometrical terms, using a model normal form equation. (c) 2004 American
      Institute of Physics.

PMID- 15446989
TI  - Pattern dynamics in a checkerboard map.
AB  - Differential equations often have solutions in the forms of trains of coherent
      structures such as pulses and antipulses. For such systems, the methods of
      singular perturbation theory permit the derivation of pattern maps that predict
      the sequence of spacings between successive pulses. Here we apply such a
      procedure to cases where two distinct kinds of pulse (or antipulse) may coexist
      in the system. In that case, direct application of the method leads to
      multivalued maps that make for complicated descriptions, especially when the
      succession of pulse types becomes chaotic. We show how this description may be
      simplified by using maps arrayed in checkerboard style to provide causal
      descriptions of both the successions of pulse spacings and the order in which the
      different kinds of pulse go by.

PMID- 15446990
TI  - Direct transition to electroconvection in a homeotropic nematic liquid crystal.
AB  - We present an experimental and theoretical investigation of a variant of
      electroconvection using an unusual nematic liquid crystal in an isotropic
      configuration (homeotropic alignment). The significance of the system is a direct
      transition to the convecting state due to the negative conductivity anisotropy
      and positive dielectric anisotropy. We observe at onset rolls or squares
      depending on the frequency and amplitude of the applied ac voltage with a strong
      signature of the zigzag instability. Good agreement with calculations based on
      the underlying hydrodynamic theory is found. We also construct an extended Swift
      Hohenberg model which allows us to capture complex patterns like squares with a
      quasiperiodic modulation.

PMID- 15446991
TI  - On thermal convection in slowly rotating systems.
AB  - The dynamical properties of convection patterns in a fluid layer heated from
      below and rotating slowly about a horizontal axis are reviewed. Applications to
      the equatorial regions of planetary and stellar atmospheres are emphasized.
      Attention is drawn to the wavelike drift of hexagonal convection cells in the
      azimuthal direction and to the mean flow generated by all convection patterns
      except for rolls aligned with the axis of rotation.

PMID- 15446992
TI  - Viscous fingering as a paradigm of interfacial pattern formation: recent results
      and new challenges.
AB  - We review recent results on dynamical aspects of viscous fingering. The Saffman
      Taylor instability is studied beyond linear stability analysis by means of a
      weakly nonlinear analysis and the exact determination of the subcritical branch.
      A series of contributions pursuing the idea of a dynamical solvability scenario
      associated to surface tension in analogy with the traditional selection theory is
      put in perspective and discussed in the light of the asymptotic theory of Tanveer
      and co-workers. The inherently dynamical singular effects of surface tension are
      clarified. The dynamical role of viscosity contrast is explored numerically. We
      find that the basin of attraction of the Saffman-Taylor finger depends on
      viscosity contrast, and that the sensitivity to this parameter is maximal in the
      usual limit of high viscosity contrast. The competing attractors are identified
      as closed bubble solutions. We briefly report on recent results and work in
      progress concerning rotating Hele-Shaw flows, topological singularities and
      wetting effects, and also discuss future directions in the context of viscous
      fingering.

PMID- 15446993
TI  - Theory of gaseous detonations.
AB  - The objective of the present paper is to review some developments that have
      occurred in detonation theory over the last ten years. They concern nonlinear
      dynamics of detonation fronts, namely patterns of pulsating and/or cellular
      fronts, selection of the cell size, dynamical self-quenching, direct (blast) or
      spontaneous initiation, and transition from deflagration to detonation. These
      phenomena are all well documented by experiments since the sixties but remained
      unexplained until recently. In the first part of the paper, the patterns of
      cellular detonations are described by an asymptotic solution to nonlinear
      hyperbolic equations (reactive Euler equations) in the form of unsteady (sometime
      chaotic) and multidimensional traveling-waves. In the second part, turning points
      of quasi-steady solutions are shown to correspond to critical conditions of fully
      unsteady problems, either for (direct or spontaneous) initiation or for
      spontaneous failure (self-quenching). Physical insights are tentatively presented
      rather than technical aspects. The challenge is to identify the physical
      mechanisms with their relevant parameters, and more specifically to explain how
      the length-scales involved in detonation dynamics are larger by two order of
      magnitude (at least) than the length-scale involved in the steady planar
      traveling-wave solution (detonation thickness).

PMID- 15446994
TI  - How much information can one store in a nonequilibrium medium?
AB  - It has recently been emphasized again that the very existence of stationary
      stable localized structures with short-range interactions might allow one to
      store information in nonequilibrium media, opening new perspectives on
      information storage. We show how to use generalized topological entropies to
      measure aspects of the quantities of storable and nonstorable information. This
      leads us to introduce a measure of the long-term stably storable information. As
      a first example to illustrate these concepts, we revisit a mechanism for the
      appearance of stationary stable localized structures that is related to the
      stabilization of fronts between structured and unstructured states (or between
      differently structured states).

PMID- 15446995
TI  - Dynamic phase separation: from coarsening to turbulence via structure formation.
AB  - We investigate some new two-dimensional evolution models belonging to the class
      of convective Cahn-Hilliard models: (i) a local model with a scalar order
      parameter, (ii) a nonlocal model with a scalar order parameter, and (iii) a model
      with a vector order parameter. These models are applicable to phase-separating
      system where concentration gradients cause hydrodynamic motion due to buoyancy or
      Marangoni effect. The numerical study of the models shows transition from
      coarsening, typical of Cahn-Hilliard systems, to spatiotemporally irregular
      behavior (turbulence), typical of the Kuramoto-Sivashinsky equation, which is
      obtained in the limit of very strong driving. The transition occurs not in a
      straightforward way, but through the formation of spatial patterns that emerge
      for intermediate values of the driving intensity. As in driven one-dimensional
      models studied before, the mere presence of the driving force, however small,
      breaks the symmetry between the two separating phases, as well as increases the
      coarsening rate. With increasing driving, coarsening stops. The dynamics is
      generally irregular at strong driving, but exhibits specific structural features.

PMID- 15446996
TI  - On propagation failure in one- and two-dimensional excitable media.
AB  - We present a nonperturbative technique to study pulse dynamics in excitable
      media. The method is used to study propagation failure in one-dimensional and two
      dimensional excitable media. In one-dimensional media we describe the behavior of
      pulses and wave trains near the saddle node bifurcation, where propagation fails.
      The generalization of our method to two dimensions captures the point where a
      broken front (or finger) starts to retract. We obtain approximate expressions for
      the pulse shape, pulse velocity, and scaling behavior. The results are compared
      with numerical simulations and show good agreement.

PMID- 15446997
TI  - Statistics of defect trajectories in spatio-temporal chaos in inclined layer
      convection and the complex Ginzburg-Landau equation.
AB  - For spatio-temporal chaos observed in numerical simulations of the complex
      Ginzburg-Landau equation (CGL) and in experiments on inclined-layer convection
      (ILC) we report numerical and experimental data on the statistics of defects and
      of defect loops. These loops consist of defect trajectories in space-time that
      are connected to each other through the pairwise annihilation or creation of the
      associated defects. While most such loops are small and contain only a few
      defects, the loop distribution functions decay only slowly with the quantities
      associated with the loop size, consistent with power-law behavior. For the CGL,
      two of the three power-law exponents are found to agree, within our computational
      precision, with those from previous investigations of a simple lattice model. In
      certain parameter regimes of the CGL and ILC, our results for the single-defect
      statistics show significant deviations from the previously reported findings that
      the defect dynamics are consistent with those of random walkers that are created
      with fixed probability and annihilated through random collisions.

PMID- 15446998
TI  - Stability of giant vortices in quantum liquids.
AB  - We show how giant vortices can be stabilized for strong external potentials in
      Bose-Einstein condensates. We illustrate the formation of these vortices thanks
      to the Ginzburg-Landau dissipative dynamics for two typical potentials in two
      spatial dimensions. The giant vortex stability is studied for the particular case
      of a rotating cylindrical hard wall. Due to axial symmetry the minimization of
      the perturbed energy is simplified into a one dimensional relaxation dynamics.
      Solving this 1D minimization problem, we observe that giant vortices are either
      never stable, or only stable in a finite frequency range. Finally we obtain the
      marginal curve for the minimum frequency needed to observe a giant vortex.

PMID- 15446999
TI  - Curvature induced periodic attractor on growth interface.
AB  - We experimentally address the long-time dynamics of an artificially curved growth
      interface in directional solidification. Repetitive cell nucleations are found to
      appear in a disordered way but to eventually organize themselves coherently, at
      long times. This behavior is recovered by simulation of a nonlinear advection
      diffusion model for the phase dynamics. The existence of a periodic attractor is
      shown by deriving a Liapunov functional for the cellular pattern organization on
      time ranges that include the singular events of cell nucleation.

PMID- 15447000
TI  - Diffusion and reaction-diffusion in fast cellular flows.
AB  - Cellular structures, as the rolls generated by Rayleigh-Benard instability, have
      always been an important topic in nonlinear science. The diffusion of a passive
      scalar in a given steady cellular flow becomes an interesting question in the
      limit of a large Peclet number, often realistic. The main result there is that
      the effective diffusion is somewhere in between the molecular diffusion and the
      "turbulent" diffusion. A new added twist to this is the reaction-diffusion case,
      where the front speed is the laminar propagation velocity (without flow) times
      the Peclet number to the power 1/4. I refine this last result and give the
      behavior of the prefactor in the Zel'dovich limit of a narrow reaction zone.

PMID- 15447001
TI  - Nonlinear Hall effect for materials with weak thermoelectric power coefficients:
      preliminary comparisons between theoretical results of the thermodynamic field
      theory and experimental data.
AB  - This paper forms a part of a series of manuscripts which we intend to submit for
      publication in the near future, aiming to test the validity of the thermodynamic
      field theory (TFT), previously formulated, comparing the theoretical results with
      experimental data. In this particular case, we shall analyze the Hall effect. As
      known, when a magnetic field is applied at right angles to the direction of an
      electric current or a thermal gradient, galvano- and thermomagnetic effects
      appear in the material. In this paper, we shall show that if we study these
      effects in nonlinear regime, the TFT foresees an interesting effect: the
      nonlinear Hall effect. This prediction is herein submitted to experimental
      verifications. In this paper, we shall analyze this effect studying materials
      with weak thermoelectric power coefficients. We shall show the agreement between
      the theoretical predictions of the TFT and experiments. Experimental curves
      related to the nonlinear Hall effect allow us to determine the order of magnitude
      of the constant chi introduced in the TFT.

PMID- 15447002
TI  - Simple ideas on mixing and fragmentation.
AB  - The mechanisms building the overall concentration distribution in a scalar
      mixture, and the drops in a spray, are examined successively. In both cases, the
      distributions belong to a unique family of distributions stable by self
      convolution, the signature of the aggregation process from which they originate.

PMID- 15447003
TI  - Dislocation dynamics in Rayleigh-Benard convection.
AB  - Theoretical results on the dynamics of dislocations in Rayleigh-Benard convection
      are reported both for a Swift-Hohenberg model and the Oberbeck-Boussinesq
      equations. For intermediate Prandtl numbers the motion of dislocations is found
      to be driven by the superposition of two independent contributions: (i) the Peach
      Koehler force and (ii) an advection force on the dislocation core by its self
      generated mean flow. Their competition allows to explain the experimentally
      observed bound dislocation pairs.

PMID- 15447004
TI  - Bifurcation analysis and existence of periodic solutions in a simple neural
      network with delays.
AB  - Results are provided here about the stability and bifurcation of periodic
      solutions for a (neural) network with n elements where delays between adjacent
      units and external inputs are included. The particular cases n = 2 and n = 3 are
      discussed in details, to explicitly illustrate the role of the delays in the
      corresponding bifurcation sets and the stability properties, like a Hopf
      bifurcation, a pitchfork bifurcation, and a Bogdanov-Takens bifurcation.

PMID- 15447005
TI  - Pioneers in biomedical optics: special section honoring Professor Watt Webb of
      Cornell University.

PMID- 15447006
TI  - Quick tour of fluorescence correlation spectroscopy from its inception.
AB  - Fluorescence correlation spectroscopy (FCS) was originally developed in the early
      1970s as a way to measure the kinetics of chemical reactions under zero
      perturbation conditions. At its inception, the measurement was difficult due to
      experimental limitations and was primarily used during the 1970s and 1980s to
      characterize diffusion. More recently, as a result of technological advances, FCS
      measurements have become easier and more versatile. In addition to measurements
      of diffusion both in solution and in cells, FCS is now also used to measure not
      only chemical reaction kinetics but also extents of molecular aggregation, the
      dynamics of photophysical processes, conformational fluctuations, molecular
      interactions in solution and in cells, and has even found application as a
      pharmaceutical screening method. From its inception to the present, the
      contributions of Webb and his coworkers have had a central and defining role in
      the development and applications of FCS.

PMID- 15447007
TI  - Regulation of pseudopodia localization in lymphocytes through application of
      mechanical forces by optical tweezers.
AB  - T-lymphocytes are responsible for cell-mediated immunity, and recognize antigens
      on target cells (e.g., tumor cells, virus-infected cells) and antigen presenting
      cells (e.g., macrophages, dendritic cells). While mechanical forces applied to a
      cell surface can produce alterations in the cytoskeletal structure, leading to
      global structural rearrangements and changes in the intracellular biochemistry
      and gene expression, it remains unknown if local mechanical forces acting at the
      lymphocyte-antigen interaction site play any role in lymphocyte activation
      following antigen recognition. In this study we investigate the effect of such
      forces induced by optical tweezers on the lymphocyte's morphological response. We
      brought optically trapped polystyrene beads, coated with a specific antibody
      against a clonotypic epitope of the T-cell receptors (TCRs), in contact with
      individual lymphocytes and applied mechanical forces at the TCR-antibody
      interaction site. Although bead size was a factor, simple bead contact tended to
      induce formation of pseudopodia that appeared randomly over the cell's surface,
      while application of tangential forces at the interaction site redirected
      pseudopodia formation toward that site and promoted endocytosis activity. We
      propose that local forces play a key role in the initial lymphocyte adhesion to
      antigen-bearing cells, and may be implicated in antigen-specific motility,
      transendothelial migration, and tissue homing to sites of inflammation.

PMID- 15447008
TI  - Second harmonic imaging of membrane potential of neurons with retinal.
AB  - We present a method to optically measure and image the membrane potential of
      neurons, using the nonlinear optical phenomenon of second harmonic generation
      (SHG) with a photopigment retinal as the chromophore [second harmonic retinal
      imaging of membrane potential (SHRIMP)]. We show that all-trans retinal, when
      adsorbed to the plasma membrane of living cells, can report on the local electric
      field via its change in SHG. Using a scanning mode-locked Ti-sapphire laser, we
      collect simultaneous two-photon excited fluorescence (TPEF) and SHG images of
      retinal-stained kidney cells and cultured pyramidal neurons. Patch clamp
      experiments on neurons stained with retinal show an increase of 25% in SHG
      intensity per 100-mV depolarization. Our data are the first demonstration of
      optical measurements of membrane potential of mammalian neurons with SHG. SHRIMP
      could have wide applicability in neuroscience and, by modifying rhodopsin, could
      in principle be subject for developing genetically engineered voltage sensors.

PMID- 15447009
TI  - Second harmonic imaging of intrinsic signals in muscle fibers in situ.
AB  - We use second harmonic generation (SHG) imaging to study and quantify a strong
      intrinsic SHG signal in skeletal muscle fiber preparations and single isolated
      myofibrils. The intrinsic signal follows the striation pattern of the muscle
      cells and is positioned at the sarcomeric location of the myosin filaments.
      Interestingly, the signal is enhanced at the region where the myosin heads are
      located on the myosin filaments. As the intrinsic signal reflects the subcellular
      structure in an accurate way, SHG can be used for noninvasive high resolution
      structural imaging without exogenous labels in living muscle cells. This may be
      very important for detecting changes in myofibrillar organization occurring under
      pathophysiological conditions, e.g., in cardiac and skeletal myopathies. Due to
      the strong dependency of SHG on orientation and symmetries of the tissue, it may
      allow the study of dynamic interactions between the contractile proteins actin
      and myosin during force production and muscle shortening. Furthermore, SHG
      imaging can be combined with other nonlinear microscopical techniques, such as
      laser scanning multiphoton fluorescence microscopy, to simultaneously measure
      other dynamic cellular processes, representing a complementary method and
      extending the range of nonlinear microscopical methods.

PMID- 15447010
TI  - From quantitative microscopy to automated image understanding.
AB  - Quantitative microscopy has been extensively used in biomedical research and has
      provided significant insights into structure and dynamics at the cell and tissue
      level. The entire procedure of quantitative microscopy is comprised of specimen
      preparation, light absorption/reflection/emission from the specimen, microscope
      optical processing, optical/electrical conversion by a camera or detector, and
      computational processing of digitized images. Although many of the latest digital
      signal processing techniques have been successfully applied to compress, restore,
      and register digital microscope images, automated approaches for recognition and
      understanding of complex subcellular patterns in light microscope images have
      been far less widely used. We describe a systematic approach for interpreting
      protein subcellular distributions using various sets of subcellular location
      features (SLF), in combination with supervised classification and unsupervised
      clustering methods. These methods can handle complex patterns in digital
      microscope images, and the features can be applied for other purposes such as
      objectively choosing a representative image from a collection and performing
      statistical comparisons of image sets.

PMID- 15447011
TI  - Parallel single molecule detection with a fully integrated single-photon 2x2 CMOS
      detector array.
AB  - We present parallel single molecule detection (SMD) and fluorescence correlation
      spectroscopy (FCS) experiments with a fully integrated complementary metal oxide
      semiconductor (CMOS) single-photon 2x2 detector array. Multifocal excitation is
      achieved with a diffractive optical element (DOE). Special emphasis is placed on
      parallelization of the total system. The performance of the novel single-photon
      CMOS detector is investigated and compared to a state-of-the-art single-photon
      detecting module [having an actively quenched avalanche photodiode (APD)] by
      measurements on free diffusing molecules at different concentrations. Despite the
      order of magnitude lower detection efficiency of the CMOS detector compared to
      the state-of-the-art single-photon detecting module, we achieve single molecule
      sensitivity and reliably determine molecule concentrations. In addition, the CMOS
      detector performance for the determination of the fraction of slowly diffusing
      molecules in a primer solution (two-component analysis) is demonstrated. The
      potential of this new technique for high-throughput confocal-detection-based
      systems is discussed.

PMID- 15447012
TI  - Two-photon laser scanning fluorescence microscopy using photonic crystal fiber.
AB  - We report the application of a simple yet powerful modular pulse compression
      system based on photonic crystal fibers that improves on incumbent two-photon
      laser scanning fluorescence microscopy techniques. This system provides more than
      a sevenfold increase in fluorescence yield when compared with a commercial two
      photon microscopy system. From this, we infer pulses of IR radiation of less than
      35 fs duration reaching the sample.

PMID- 15447013
TI  - New fluorescence imaging probe with high spatial resolution for in vivo
      applications.
AB  - A new fiberized fluorescence imaging probe is presented. This device can
      potentially be used for a wide range of biological or medical applications. By
      exploiting the chromatic aberrations of gradient index lenses, the excitation
      blue or near-UV excitation light is focused on the sample surface, while the red
      fluorescence signal is efficiently launched back to collecting fibers. The
      excitation fiber is single mode at the working wavelength so that a resolution of
      5 microm is obtained over a scanning area of several square millimeters.
      Experimental fluorescence images are presented. They concern either self
      fabricated fluorescent microsamples or views of leaves that constitute an example
      of biological tissues analysis. The probe can also be adapted for spectroscopic
      investigations.

PMID- 15447014
TI  - Comparison of aminolevulinic-acid-induced fluorescence from normal and inflamed
      gingiva in the canine model.
AB  - Fluorescence spectroscopic detection using 5-amino levulinic acid (ALA) may
      provide an effective, noninvasive approach for early detection of oral cancer. In
      the present study, the use of ALA-induced fluorescence ratio (red/orange) to
      differentiate between normal and gingivitis-affected gingiva is investigated.
      Five dogs with varying degrees of gingivitis are studied. Based on previous
      studies, a dose of 25 mg/kg of ALA is administered intravenously to the dogs.
      Autofluorescence and ALA-induced fluorescence from three sites: normal gingiva,
      pigmented gingiva, and gingivitis, are detected with a fiber optic probe coupled
      to an optical multichannel analyzer. Four dogs show higher and earlier ALA
      induced fluorescence from the gingivitis site as compared to the unpigmented
      gingiva. In two dogs, ALA-induced fluorescence peaks are seen 15 min after ALA
      administration. Statistical analysis using mean separation procedures reveal
      differences in the fluorescence from the various sites in each dog. Using a
      fluorescence (ratio) cutoff of 1.5, the sensitivity and specificity are found to
      be 92 and 80%, respectively, 1 h after administration of ALA. The indications
      from this study-that the characteristic protoporphyrin IX (PpIX) fluorescence is
      seen earlier and in higher magnitude in more vascular areas of the oral cavity
      has implications for oral cancer diagnosis.

PMID- 15447015
TI  - Clinical study for classification of benign, dysplastic, and malignant oral
      lesions using autofluorescence spectroscopy.
AB  - Autofluorescence spectroscopy shows promising results for detection and staging
      of oral (pre-)malignancies. To improve staging reliability, we develop and
      compare algorithms for lesion classification. Furthermore, we examine the
      potential for detecting invisible tissue alterations. Autofluorescence spectra
      are recorded at six excitation wavelengths from 172 benign, dysplastic, and
      cancerous lesions and from 97 healthy volunteers. We apply principal components
      analysis (PCA), artificial neural networks, and red/green intensity ratio's to
      separate benign from (pre-)malignant lesions, using four normalization
      techniques. To assess the potential for detecting invisible tissue alterations,
      we compare PC scores of healthy mucosa and surroundings/contralateral positions
      of lesions. The spectra show large variations in shape and intensity within each
      lesion group. Intensities and PC score distributions demonstrate large overlap
      between benign and (pre-)malignant lesions. The receiver-operator characteristic
      areas under the curve (ROC-AUCs) for distinguishing cancerous from healthy tissue
      are excellent (0.90 to 0.97). However, the ROC-AUCs are too low for
      classification of benign versus (pre-)malignant mucosa for all methods (0.50 to
      0.70). Some statistically significant differences between
      surrounding/contralateral tissues of benign and healthy tissue and of (pre
      )malignant lesions are observed. We can successfully separate healthy mucosa from
      cancers (ROC-AUC>0.9). However, autofluorescence spectroscopy is not able to
      distinguish benign from visible (pre-)malignant lesions using our methods (ROC
      AUC<0.65). The observed significant differences between healthy tissue and
      surroundings/contralateral positions of lesions might be useful for invisible
      tissue alteration detection.

PMID- 15447016
TI  - Differential oblique angle spectroscopy of the oral epithelium.
AB  - Increasing evidence suggests that inflammation may contribute to the process of
      carcinogenesis. This is the basis of several clinical trials evaluating potential
      chemopreventive drugs. These trials require quantitative assessments of
      inflammation, which, for the oral epithelium, are traditionally provided by
      histopathological evaluation. To reduce patient discomfort and morbidity of
      tissue biopsy procedures, we develop a noninvasive alternative using diffuse
      reflectance spectroscopy to measure epithelial thickness as an index of tissue
      inflammation. Although any optical system has the potential for probing near
      surface structures, traditional methods of accounting for scattering of photons
      are generally invalid for typical epithelial thicknesses. We develop a single
      scattering theory that is valid for typical epithelial thicknesses. The theory
      accurately predicts a distinctive feature that can be used to quantify epithelial
      thickness given intensity measurements with sources at two different angles
      relative to the tissue surface. This differential measure approach has acute
      sensitivity to small, layer-related changes in scattering coefficients. To assess
      the capability of our method to quantify epithelial thickness, detailed Monte
      Carlo simulations and measurements on phantom models of a two-layered structure
      are performed. The results show that the intensity ratio maximum feature can be
      used to quantify epithelial thickness with an error less than 30% despite
      fourfold changes in scattering coefficients and 10-fold changes in absorption
      coefficients. An initial study using a simple two-source, four-detector probe on
      patients shows that the technique has promise. We believe that this new method
      will perform well on patients with diverse tissue optical characteristics and
      therefore be of practical clinical value for quantifying epithelial thickness in
      vivo.

PMID- 15447017
TI  - Accurate measurement of blood vessel depth in port wine stained human skin in
      vivo using pulsed photothermal radiometry.
AB  - We report on application of pulsed photothermal radiometry (PPTR) to determine
      the depth of port wine stain (PWS) blood vessels in human skin. When blood
      vessels are deep in the PWS skin (>100 microm), conventional PPTR depth profiling
      can be used to determine PWS depth with sufficient accuracy. When blood vessels
      are close or partially overlap the epidermal melanin layer, a modified PPTR
      technique using two-wavelength (585 and 600 nm) excitation is a superior method
      to determine PWS depth. A direct difference approach in which PWS depth is
      determined from a weighted difference of temperature profiles reconstructed
      independently from two-wavelength excitation is demonstrated to be appropriate
      for a wider range of PWS patients with various blood volume fractions, blood
      vessel sizes, and depth distribution. The most superficial PWS depths determined
      in vivo by PPTR are in good agreement with those measured using optical Doppler
      tomography (ODT).

PMID- 15447018
TI  - Constrained optimization of Drude's equations eliminates effects of confounding
      molecules for the polarimetric measurement of glucose.
AB  - Common confounding factors for polarimetric concentration measurements include
      additional optical rotations from unknown optically active molecules, linear
      birefringence of the medium, and path length variability. We show that by
      approximating Drude's equation and taking several measurements from the same
      sample at different wavelengths, the error due to confounding rotations in the
      measurements can theoretically be canceled. The analysis is developed with regard
      to glucose sensing in aqueous humor. First, we show that the optical rotatory
      dispersions of the known molecules in bovine aqueous humor could be represented
      by Drude's equations. Then, the total optical rotation is approximated by a
      function combining Drude's equations for the major contributors in the sample,
      i.e., glucose, glutamine, fructose, and phenylalanine. The concentration-related
      unknown coefficients in the approximating function are found by constrained
      nonlinear optimization of the function at different wavelengths. This technique
      is tested on a published data set and four alterations of those data: (1)
      concentrations randomly varied within narrow limits, (2) similar to alteration 1
      but with significantly elevated glucose concentration, (3) similar to alteration
      1 but with significantly decreased glucose concentration, and (4) concentrations
      randomly varied within wider limits than alteration 1. The method produces very
      accurate glucose-concentration estimates in all of these data sets. The relative
      error was smaller than 1% in all except the low-glucose sample (1.4%). This
      method may prove useful in noninvasive glucose measurement in humans.

PMID- 15447019
TI  - Optical coherence tomography of malignancy in hamster cheek pouches.
AB  - Optical coherence tomography (OCT)/optical Doppler tomography (ODT) provides real
      time in vivo high-resolution (10-microm) imaging of tissues and real-time
      spatially resolved blood flow in microvasculature. Hamster cheek pouches with
      induced dysplasia and malignancies were imaged with OCT/ODT to assess the
      potential for application to airway malignancy. In 22 Golden Syrian hamsters,
      0.5% 9,10-dimethyl-1,2-benzanthracene induces carcinogenesis over 10 weeks in
      right side cheek pouches; the left side three served as controls. The cheek
      pouches are imaged in vivo prior to sacrifice, and in vitro after excision, using
      a prototype 1310-nm broadband superluminescent diode based OCT/ODT device. Images
      are compared to standard histopathology. OCT imaging offers good resolution of
      the hamster cheek pouches to depths of 1 to 3 mm and paralleled histologic
      images. The feasibility of high-resolution functional imaging is demonstrated in
      this hamster cheek pouch tumor model. ODT accurately detects vascular change
      associated with carcinogenesis.

PMID- 15447020
TI  - Measuring red blood cell flow dynamics in a glass capillary using Doppler optical
      coherence tomography and Doppler amplitude optical coherence tomography.
AB  - Blood, being a suspension of deformable red cells suspended in plasma, displays
      flow dynamics considerably more complicated than those of an ideal Newtonian
      fluid. Flow dynamics in blood capillaries of a few hundred micrometers in
      diameter are investigated using Doppler optical coherence tomography (DOCT) and
      Doppler amplitude optical coherence tomography (DAOCT), a novel extension of
      DOCT. Velocity profiles and concentration distributions of normal and rigidified
      in vitro red blood cell suspensions are shown to vary as functions of mean flow
      velocity, cell concentration, and cell rigidity. Deviation from the parabolic
      velocity profile expected for Pouseille flow is observed for both rigid and
      normal cells at low flow rates. Axial red cell migration both toward and away
      from the tube axis is observed for both rigid and normal cells as a function of
      flow velocity. Good agreement is found between our measurements, and theoretical
      expectations.

PMID- 15447021
TI  - Blood cell counting and classification by nonflowing laser light scattering
      method.
AB  - We present a nonflowing laser light scattering method for automatically counting
      and classifying blood cells. A linear charge-coupled device (CCD) and a silicon
      photoelectric cell (which is placed behind a pinhole plate on the CCD) form a
      double-detector structure: the CCD is used to detect the scattered light
      intensity distribution of the blood cells and the silicon photoelectric cell to
      complete the focusing process. An isotropic sphere, with relative refractivity
      near 1, is used to model the blood cell. Mie theory is used to describe the
      scattering of white blood cells and platelets, and anomalous diffraction, red
      blood cells. To obtain the size distribution of blood cells from their scattered
      light intensity distribution, the nonnegative constraint least-squares (NNLS)
      method combined with the Powell method and the precision punishment method are
      used. Both numerical simulation and experimental results are presented. This
      method can be used not only to measure the mean and the distribution of red blood
      cell size, but also to divide the white blood cells into three classes:
      lymphocytes, middle-sized cells, and neutrocytes. The experimental results show a
      linear relationship between the blood cell (both white and red blood cells)
      concentration and the scattered light intensity, and therefore, the number of
      blood cells in a unit volume can be determined from this relationship.

PMID- 15447022
TI  - Reconstruction of optical properties of low-scattering tissue using derivative
      estimated through perturbation Monte-Carlo method.
AB  - An iterative method for the reconstruction of optical properties of a low
      scattering object, which uses a Monte-Carlo-based forward model, is developed. A
      quick way to construct and update the Jacobian needed to reconstruct a
      discretized object, based on the perturbation Monte-Carlo (PMC) approach, is
      demonstrated. The projection data is handled either one view at a time, using a
      propagation-backpropagation (PBP) strategy where the dimension of the inverse
      problem and consequently the computation time are smaller, or, when this approach
      failed, using all the views simultaneously with a full dataset. The main
      observations and results are as follows. 1. Whereas the PMC gives an accurate and
      quick method for constructing the Jacobian the same, when adapted to update the
      computed projection data, the data are not accurate enough for use in the
      iterative reconstruction procedure leading to convergence. 2. The a priori
      assumption of the location of inhomogeneities in the object reduces the dimension
      of the problem, leading to faster convergence in all the cases considered, such
      as an object with multiple inhomogeneities and data handled one view at a time
      (i.e., the PBP approach). 3. On the other hand, without a priori knowledge of the
      location of inhomogeneities, the problem was too ill posed for the PBP approach
      to converge to meaningful reconstructions when both absorption and scattering
      coefficients are considered as unknowns. Finally, to bring out the effectiveness
      of this method for reconstructing low-scattering objects, we apply a diffusion
      equation-based algorithm on a dataset from one of the low-scattering objects and
      show that it fails to reconstruct object inhomogeneities.

PMID- 15447023
TI  - Influence of uterine cervix shape on photodynamic therapy efficiency.
AB  - The goal of practical photodynamic therapy (PDT) dosimetry is to optimize the
      distribution of a light dose delivered to tissue by selecting the irradiation
      time and geometry to match the geometry and optical properties of the tumor and
      surrounding tissue. Homogeneous irradiation is among one of the sources of
      correct PDT dosimetry. The goal of this study is to model and predict the
      influence of the shape of a treated organ in need of light dose correction. Thus
      efficiency of light delivery to the tissue volume is defined and calculated with
      shape factors of the uterine cervix as parameters. Two cases (parallel and
      divergent beam) of enlightening configuration are investigated. The calculations
      presented extend PDT dosimetry with the influence of the shape of the uterine
      cervix on PDT necrosis depth. This allows for photodynamic excitation light dose
      correction for more reliable treatments.

PMID- 15447024
TI  - In vivo assessment of thermal damage in the liver using optical spectroscopy.
AB  - Resection is not a viable treatment option for the majority of liver cancer
      patients. Alternatives to resection include thermotherapies such as radio
      frequency ablation; however, these therapies lack adequate intraoperative
      feedback regarding the degree and margins of tissue thermal damage. In this proof
      of principle study, we test the ability of fluorescence and diffuse reflectance
      spectroscopy to assess local thermal damage in vivo. Spectra were acquired in
      vivo from healthy canine liver tissue undergoing radio-frequency ablation using a
      portable fiber-optic-based spectroscopic system. The major observed spectral
      alterations on thermal coagulation were a red shift in the fluorescence emission
      peak at 480 nm, a decrease in the overall fluorescence intensity, and an increase
      in the diffuse reflectance from 450 to 750 nm. Spectral changes were quantified
      and correlated to tissue histology. We found a good correlation between the
      proposed spectral correlates of thermal damage and histology. The results of this
      study suggest that fluorescence and diffuse reflectance spectroscopy show strong
      potential as tools to monitor liver tissue thermal damage intraoperatively.

PMID- 15447025
TI  - Tissue spectroscope: a novel in vivo approach to real time monitoring of tissue
      vitality.
AB  - Optical monitoring of various tissue physiological and biochemical parameters in
      real-time represents a significant new approach and a tool for better clinical
      diagnosis. The Tissue Spectroscope (TiSpec), developed and applied in
      experimental and clinical situations, is the first medical device that enables
      the real-time monitoring of three parameters representing the vitality of the
      tissue. Tissue vitality, which is correlated to the oxygen balance in the tissue,
      is defined as the ratio between O(2) supply and O(2) demand. The TiSpec enables
      the monitoring of microcirculatory blood flow (O(2) supply), mitochondrial NADH
      redox state (O(2) balance), and tissue reflectance, which correlates to blood
      volume. We describe in detail the theoretical basis for the monitoring of the
      three parameters and the technological aspects of the TiSpec. The comparison
      between the TiSpec and the existing single parameter monitoring instruments shows
      a statistically significant correlation as evaluated in vitro as well as in
      various in vivo animal models. The results presented originated in a pilot study
      performed in vivo in experimental animals. Further research is needed to apply
      this technology clinically. The clinical applications of the TiSpec include two
      situations where the knowledge of tissue vitality can improve clinical practice.
      The major application is the monitoring of "nonvital" organs of the body [i.e.,
      the skin, gastrointestinal (G-I) tract, urethra] in emergency situations, such as
      in the operating rooms and intensive care units. Also, the monitoring of specific
      (vital) organs, such as the brain or the heart, during surgical procedure is of
      practical importance.

PMID- 15447026
TI  - Three-dimensional optical tomographic brain imaging in small animals, part 1:
      hypercapnia.
AB  - In this study, we explore the potential of diffuse optical tomography for brain
      oximetry. While several groups have already reported on the sensitivity of
      optical measurements to changes in oxyhemoglobin, deoxyhemoglobin, and blood
      volume, these studies were often limited to single source-detector geometries or
      topographic maps, where signals obtained from within the brain are projected onto
      2-D surface maps. In this two-part study, we report on our efforts toward
      developing a volumetric optical imaging system that allows one to spatially
      resolve 3-D hemodynamic effects in rat brains. In part 1, we describe the
      instrumentation, optical probe design, and the model-based iterative image
      reconstruction algorithm employed in this work. Consideration of how a priori
      anatomical knowledge can be incorporated in the reconstruction process is
      presented. This system is then used to monitor global hemodynamic changes that
      occur in the brain under various degrees of hypercapnia. The physiologic cerebral
      response to hypercapnia is well known and therefore allows an initial performance
      assessment of the imaging system. As expected, we observe global changes in blood
      volume and oxygenation, which vary linearly as a function of the concentration of
      the inspired carbon dioxide. Furthermore, experiments are designed to determine
      the sensitivity of the reconstructions of only 1 mm to inaccurate probe
      positioning. We determine that shifts can significantly influence the
      reconstructions. In part 2 we focus on more local hemodynamic changes that occur
      during unilateral carotid occlusion performed at lower-than-normal systemic blood
      pressure. In this case, the occlusion leads to a predominantly
      monohemispherically localized effect, which is well described in the literature.
      Having explored the system with a well-characterized physiologic effect, we
      investigate and discuss the complex compensatory cerebrovascular hemodynamics
      that occur at normotensive blood pressure. Overall, these studies demonstrate the
      potential and limitations of our diffuse optical imager for visualizing global
      and focal hemodynamic phenomenon three dimensionally in the brains of small
      animals.

PMID- 15447027
TI  - Three-dimensional optical tomographic brain imaging in small animals, part 2:
      unilateral carotid occlusion.
AB  - This is the second part of a two-part study that explores the feasibility of 3-D,
      volumetric brain imaging in small animals by optical tomographic techniques. In
      part 1, we demonstrated the ability to visualize global hemodynamic changes in
      the rat head in response to elevated levels of CO(2) using a continuous-wave
      instrument and model-based iterative image reconstruction (MOBIIR) algorithm. Now
      we focus on lateralized, monohemispherically localized hemodynamic effects
      generated by unilateral common carotid artery (CCA) occlusion. This illustrates
      the capability of our optical tomographic system to localize and distinguish
      hemodynamic responses in different parts of the brain. Unilateral carotid
      occlusions are performed in ten rodents under two experimental conditions. In the
      first set of experiments the normal systemic blood pressure is lowered to 50
      mmHg, and on unilateral carotid occlusion, we observe an ipsilateral
      monohemispheric global decrease in blood volume and oxygenation. This finding is
      consistent with the known physiologic response to cerebral ischemia. In a second
      set of experiments designed to observe the spatial-temporal dynamics of CCA
      occlusion at normotensive blood pressure, more complex phenomena are observed. We
      find three different types of responses, which can be categorized as
      compensation, overcompensation, and noncompensation.

PMID- 15447028
TI  - Contaminant effect on cellular metabolic differential pressure curves.
AB  - The possibility of a pressure monitoring system by differential pressure sensors
      to detect contaminant effects on cellular cultures metabolic activity is
      discussed using Saccharomyces cerevisiae, lymphocyte, and AHH1 cell cultures.
      Metabolic (aerobic and anaerobic) processes in cells are accompanied by CO(2)
      production that induces changes in pressure values when cells are cultured in
      sealed vessels. These values are subsequently converted in voltage units and
      plotted pressure dynamics versus time. This procedure leads to a standard curve,
      typical of the cellular line, which characterizes cellular metabolism when all
      parameters are controlled, such as temperature and nutrients. Different phases
      appear in the S. cerevisiae differential pressure curve: an initial growth up to
      a maximum, followed by a decrement that leads to a typical "depression" (pressure
      values inside the test-tubes are lower than the initial one) after about 35 h
      from the beginning. The S. cerevisiae differential pressure curve is successfully
      used to test the effects of chemical (Amuchina, trieline) and physical (UV
      radiation, blue light, magnetic fields) contaminants. The same technique is
      applied to lymphocytes and AHH1 cultures to investigate the effects generated by
      a 72-h exposure to a 50-Hz, 60-microT electromagnetic field. Lymphocyte samples,
      cultured in a PHA medium, grow less than control ones, but exhibit a greater
      metabolic activity: changes in the exposure system configuration influence
      neither sample growth differences nor metabolic response variations between
      control and irradiated samples, while all the other irradiation parameters remain
      constant. Control and irradiated lymphocyte samples, without PHA in culture
      medium, show the same behavior both during irradiation and metabolic test. AHH1
      control and irradiated samples show no difference both in growth percentage
      during irradiation and in metabolic activity. Different cell cultures respond to
      the same stimulus in different manners.

PMID- 15447029
TI  - Photochemical tissue bonding using monomeric 4-amino-1,8-naphthalimides.
AB  - Certain substituted naphthalimides have been shown to produce, on photochemical
      activation, mechanically viable bonds between a variety of tissue surfaces. It is
      believed that these compounds act as photochemically activated oxidants,
      catalyzing the formation of reactive intermediates in the extracellular matrices
      of approximated tissue surfaces. The condensation of these intermediates results
      in the formation of crosslinks between the intimate surfaces. Of particular
      interest is the application of this technique to the repair of tears in the
      typically unrepairable avascular zone of menisci. The menisci are collagen-rich
      fibrocartilaginous tissues that support up to 90% of the load across the knee
      joint and participate in important functions including shock absorption, joint
      stabilization, hyperextension prevention, and lubrication of the knee.
      Preliminary ex vivo and in vivo work in our laboratories has demonstrated that
      photochemically activated naphthalimides have significant potential for the
      repair of meniscal lesions. We describe preliminary ex vivo studies assessing the
      relative abilities of a variety of water-soluble monomeric 4-amino-1,8
      naphthalimides to bond bovine knee meniscal tissue on visible light irradiation.

PMID- 15447030
TI  - Computer model to investigate the effect of eye movements on retinal heating
      during long-duration fixation on a laser source.
AB  - A computer simulation called RHME (Retinal Heating in Moving Eye) is developed to
      simulate the heating pattern that occurs in the retina during a long-duration
      exposure to a continuous wave laser beam. The simulation takes into account eye
      movements that occur during a deliberate fixation. Due to the rapid (millisecond)
      thermal time scale for heating and cooling, only the area of the retina directly
      exposed to the laser sustains an increased temperature. Once the laser spot is
      removed from a particular location of the retina (because of eye movements) that
      location quickly cools. Points of the retina will therefore have a complex
      thermal history during a long-duration exposure. Simulation results for a minimal
      retinal spot size indicate that subjects staring at a helium-neon laser
      (lambda=632.8 nm) beam producing the small-source maximum permissible exposure
      (MPE) level corneal irradiance of 1 mW cm(-2) (>10-s exposure) will experience a
      maximum although transient temperature increase in the retina of less than 2
      degrees C during a 50-s fixation trial. The large increase in the International
      Commission on Non-Ionizing Radiation Protection (ICNIRP) and ANSI Z136.1 safety
      limits for a long-duration small-source exposure to visible continuous wave
      lasers that was adopted in 2000 therefore appears appropriate.

PMID- 15447031
TI  - Automated detection of ocular focus.
AB  - We characterize objectively the state of focus of the human eye, utilizing a
      bull's eye photodetector to detect the double-pass blur produced from a point
      source of light. A point fixation source of light illuminates the eye. Fundus
      reflected light is focused by the optical system of the eye onto a bull's eye
      photodetector [consisting of an annulus (A) and a center (C) of approximately
      equal active area]. To generate focus curves, C/A is measured with a range of
      trial lenses in the light path. Three human eyes and a model eye are studied. In
      the model eye, the focus curve showed a sharp peak with a full width at half
      maximum (FWHM) of +/-0.25 D. In human eyes, the ratio C/A was >4 at best focus in
      all cases, with a FWHM of +/-1 D. The optical apparatus detects ocular focus (as
      opposed to refractive error) in real time. A device that can assess focus rapidly
      and objectively will make it possible to perform low-cost, mass screening for
      focusing problems such as may exist in children at risk for amblyopia.

PMID- 15447033
TI  - Microdosimetry of electron microbeams.
AB  - Track structures of 25, 50 and 80 keV primary electrons, simulated by the
      detailed-history Monte Carlo method, were analyzed for the frequency
      distributions of energy deposited in spheres with a diameter of 1 microm, placed
      in a cylindrically symmetrical array around the projected initial direction of
      the primary electron. The frequency mean of specific energy, the dose mean of
      lineal energy, and the parameters of lognormal functions fit to the dose
      distributions were calculated as a function of beam penetration and radial
      distance from the projected beam axis. Given these data, the stochastics of dose
      and radiation quality for micrometer-scale sites targeted by a medium-energy
      electron microbeam can be predicted as a function of the site's location relative
      to the beam entry point.

PMID- 15447034
TI  - EPR studies of 5-bromouracil crystal after irradiation with X rays in the bromine
      K-edge region.
AB  - Radicals induced in a single crystal of 5-bromouracil (BrUra) by synchrotron soft
      X rays in the bromine K-edge region (13.461-13.482 keV) were investigated using
      the X-band EPR method. The crystal was irradiated at three peak energies of the
      absorption spectrum at room temperature or at 80 K. A hydrogen abstraction
      radical derived from N1 of the pyrimidine ring was commonly observed for all of
      the energies used, though with some variation in quantity. Similar
      characteristics were also observed in the EPR signal for the off-K-edge low
      energy (13.42 keV) and (60)Co gamma rays used for comparison. When irradiated at
      80 K, a much larger exposure (roughly 10 times) of soft X rays was needed to
      obtain the same signal intensity as that observed at room temperature. EPR
      signals were not detectable with gamma irradiation at liquid nitrogen
      temperature.

PMID- 15447035
TI  - Photoabsorption study of Bacillus megaterium, DNA and related biological
      materials in the phosphorus K-shell edge region.
AB  - We measured the X-ray transmission spectra of several biologically related
      samples in the phosphorus K-shell edge absorption region. These include red
      phosphorus, hydrated sodium phosphate (Na(3)PO(4).12 H(2)O), deoxyribonucleic
      acid (DNA), adenosine triphosphate (ATP), diolylphosphatidyl choline (DOPC), and
      Bacillus megaterium spores. Red phosphorus essentially displays an edge-jump. All
      other spectra are similar in form and energy position: Each is dominated by a
      narrower, more intense first peak and a broader but less intense second peak. The
      corresponding K-shell edge absorption thresholds are shifted toward higher energy
      relative to that for red phosphorus, as expected for increasing degrees of
      phosphorus oxidation. The B. megaterium spectrum has aspects common to both the
      phosphate and DNA spectra and is therefore interpreted as a composite of spectra
      arising from DNA, ribonucleic acid (RNA) and phosphates within the spore. The B.
      megaterium spore spectrum provides information for resonant radiation damage
      studies in the phosphorus K-shell edge absorption region by identifying candidate
      photoexcitations. In addition, the absorption spectra will be useful in X-ray
      microscopy and macromolecular crystallography studies at the phosphorus K-shell
      edge.

PMID- 15447036
TI  - A Monte Carlo model of DNA double-strand break clustering and rejoining kinetics
      for the analysis of pulsed-field gel electrophoresis data.
AB  - In studies of radiation-induced DNA fragmentation and repair, analytical models
      may provide rapid and easy-to-use methods to test simple hypotheses regarding the
      breakage and rejoining mechanisms involved. The random breakage model, according
      to which lesions are distributed uniformly and independently of each other along
      the DNA, has been the model most used to describe spatial distribution of
      radiation-induced DNA damage. Recently several mechanistic approaches have been
      proposed that model clustered damage to DNA. In general, such approaches focus on
      the study of initial radiation-induced DNA damage and repair, without considering
      the effects of additional (unwanted and unavoidable) fragmentation that may take
      place during the experimental procedures. While most approaches, including
      measurement of total DNA mass below a specified value, allow for the occurrence
      of background experimental damage by means of simple subtractive procedures, a
      more detailed analysis of DNA fragmentation necessitates a more accurate
      treatment. We have developed a new, relatively simple model of DNA breakage and
      the resulting rejoining kinetics of broken fragments. Initial radiation-induced
      DNA damage is simulated using a clustered breakage approach, with three free
      parameters: the number of independently located clusters, each containing several
      DNA double-strand breaks (DSBs), the average number of DSBs within a cluster
      (multiplicity of the cluster), and the maximum allowed radius within which DSBs
      belonging to the same cluster are distributed. Random breakage is simulated as a
      special case of the DSB clustering procedure. When the model is applied to the
      analysis of DNA fragmentation as measured with pulsed-field gel electrophoresis
      (PFGE), the hypothesis that DSBs in proximity rejoin at a different rate from
      that of sparse isolated breaks can be tested, since the kinetics of rejoining of
      fragments of varying size may be followed by means of computer simulations. The
      problem of how to account for background damage from experimental handling is
      also carefully considered. We have shown that the conventional procedure of
      subtracting the background damage from the experimental data may lead to
      erroneous conclusions during the analysis of both initial fragmentation and DSB
      rejoining. Despite its relative simplicity, the method presented allows both the
      quantitative and qualitative description of radiation-induced DNA fragmentation
      and subsequent rejoining of double-stranded DNA fragments.

PMID- 15447037
TI  - The linear no-threshold model does not hold for low-dose ionizing radiation.
AB  - Almost all of the data on the biological effects of ionizing radiation come from
      studies of high doses. However, the human population is unlikely to be exposed to
      such doses. Regulatory limits for radiation exposure are based on the linear no
      threshold model, which predicts that the relationship between biological effects
      and radiation dose is linear, and that any dose has some effect. Chromosomal
      changes are an important effect of ionizing radiation because of their role in
      carcinogenesis. Here we exposed pKZ1 mice to single whole-body X-radiation doses
      as low as 1 microGy. We observed three different phases of response: (1) an
      induction of inversions at ultra-low doses, (2) a reduction below endogenous
      inversion frequency at low doses, and (3) an induction of inversions again at
      higher doses. These results do not fit a linear no-threshold model, and they may
      have implications for the way in which regulatory standards are presently set and
      for understanding radiation effects.

PMID- 15447038
TI  - Indicators of hippocampal neurogenesis are altered by 56Fe-particle irradiation
      in a dose-dependent manner.
AB  - The health risks to astronauts exposed to high-LET radiation include possible
      cognitive deficits. The pathogenesis of radiation-induced cognitive injury is
      unknown but may involve loss of neural precursor cells from the subgranular zone
      (SGZ) of the hippocampal dentate gyrus. To address this hypothesis, adult female
      C57BL/6 mice received whole-body irradiation with a 1 GeV/nucleon iron-particle
      beam in a single fraction of 0, 1, 2 and 3 Gy. Two months later mice were given
      BrdU injections to label proliferating cells. Subsequently, hippocampal tissue
      was assessed using immunohistochemistry for detection of proliferating cells and
      immature neurons. Routine histopathological methods were used to qualitatively
      assess tissue/cell morphology in the hippocampal formation and adjacent areas.
      When compared to controls, irradiated mice showed progressively fewer BrdU
      positive cells as a function of dose. This observation was confirmed by Ki-67
      immunostaining in the SGZ showing reductions in a dose-dependent fashion. The
      progeny of the proliferating SGZ cells, i.e. immature neurons, were visualized by
      doublecortin staining and were significantly reduced by irradiation, with the
      decreases ranging from 34% after 1 Gy to 71% after 3 Gy. Histopathology showed
      that in addition to cell changes in the SGZ, (56)Fe particles induced a chronic
      and diffuse astrocytosis and changes in pyramidal neurons in and around the
      hippocampal formation. The present data provide the first evidence that high-LET
      radiation has deleterious effects on cells associated with hippocampal
      neurogenesis.

PMID- 15447039
TI  - Radiosensitization by hyperthermia in the chicken B-lymphocyte cell line DT40 and
      its derivatives lacking nonhomologous end joining and/or homologous recombination
      pathways of DNA double-strand break repair.
AB  - Hyperthermia has a radiosensitizing effect, which is one of the most important
      biological bases for its use in cancer therapy with radiation. Although the
      mechanism of this effect has not been clarified in molecular terms, possible
      involvement of either one or both of two major DNA double-strand break (DSB)
      repair pathways, i.e. nonhomologous end joining (NHEJ) and homologous
      recombination (HR), has been speculated. To test this possibility, we examined
      cells of the chicken B-lymphocyte cell line DT40 and its derivatives lacking NHEJ
      and/or HR: KU70(-/-), DNA-PKcs(-/-/-), RAD54(-/-) and KU70(-/-)/RAD54(-/-).
      Radiosensitization by hyperthermia could be seen in all of the mutants, including
      KU70(-/-)/RAD54(-/-), which lacked both NHEJ and HR. Therefore,
      radiosensitization by hyperthermia cannot be explained simply by its inhibitory
      effects, if any, on NHEJ and/or HR alone. However, in NHEJ-defective KU70(-/-)
      and DNA-PKcs(-/-/-), consisting of two subpopulations with distinct
      radiosensitivity, the radiosensitive subpopulation, which is considered to be
      cells in G(1) and early S, was not sensitized. Substantial sensitization was seen
      only in the radioresistant subpopulation, which is considered to be cells in late
      S and G(2), capable of repairing DSBs through HR. This observation did not
      exclude possible involvement of NHEJ in G(1) and early S phase and also suggested
      inhibitory effects of hyperthermia on HR. Thus partial contribution of NHEJ and
      HR in radiosensitization by hyperthermia, especially that depending on the cell
      cycle stage, remains to be considered.

PMID- 15447040
TI  - Biological responses in known bystander cells relative to known microbeam
      irradiated cells.
AB  - Normal human fibroblasts in plateau phase ( congruent with 95% G(1) phase) were
      stained with the vital nuclear dye Hoechst 33342 (blue fluorescence) or the vital
      cytoplasmic dye Cell Tracker Orange (orange fluorescence) and plated at a ratio
      of 1:1. Only the blue-fluorescing nuclei were microbeam-irradiated with a defined
      number of 90 keV/microm alpha particles. The orange-fluorescing cells were then
      "bystanders", i.e. not themselves hit but adjacent to cells that were. Hit cells
      showed a fluence-dependent induction of micronuclei as well as delays in
      progression from G(1) to S phase. Known bystander cells also showed enhanced
      frequencies of micronuclei (intermediate between those seen in irradiated and
      control cells) and transient cell cycle delays. However, the induction of
      micronuclei in bystander cells did not appear to be dependent on the fluence of
      the particles delivered to the neighboring hit cells. These are the first studies
      in which the bystander effect has been visualized directly rather than inferred.
      They indicate that the phenomenon has a quantitative basis and imply that the
      target for radiation effects cannot be considered to be the individual cell.

PMID- 15447041
TI  - Increases in oxidative stress in the progeny of X-irradiated cells.
AB  - A number of phenotypes persist in the progeny of irradiated cells for many
      generations including delayed reproductive death, cell transformation, genomic
      instability, and mutations. It appears likely that persistent phenotypes are
      inherited by an epigenetic mechanism, although very little is known about the
      nature of such a mechanism or how it is established. One hypothesis is that
      radiation causes a heritable increase in oxy-radical activity. In the present
      study, intracellular levels of reactive oxygen species (ROS) in human lymphoblast
      clones derived from individually X-irradiated cells were monitored for about 55
      generations after exposure. A number of clones derived from irradiated cells had
      an increase in dichlorofluorescein (DCF) fluorescence at various times. Cells
      with abrogated TP53 expression had a decreased oxidant response. Flow cytometry
      analysis of clones with increased fluorescence did not detect increases in the
      sub-G(1) fraction or decreased cell viability compared to nonirradiated clones,
      indicating that increased levels of apoptosis and cell death were not present.
      The oxidative stress response protein heme oxygenase 1 (HO1) was induced in some
      cultures derived from X-irradiated cells but not in cultures derived from
      unirradiated cells. The expression of the dual specificity mitogen-activated
      protein (MAP) kinase phosphatase (MPK1/CL100), which is inducible by oxidative
      stress and has a role in modulating ERK signaling pathways, was also increased in
      the progeny of some irradiated cells. Finally, there was an increase in the
      phosphorylated tyrosine content of a prominent protein band of about 45 kDa.
      These results support the hypothesis that increased oxy-radical activity is a
      persistent effect in X-irradiated mammalian cells and further suggest that this
      may lead to changes in the expression of proteins involved in signal
      transduction.

PMID- 15447042
TI  - The response of malignant B lymphocytes to ionizing radiation: cell cycle arrest,
      apoptosis and protection against the cytotoxic effects of the mitotic inhibitor
      nocodazole.
AB  - Ionizing radiation and mitotic inhibitors are used for the treatment of lymphoma.
      We have studied cell cycle arrest and apoptosis of three human B-lymphocyte cell
      lines after X irradiation and/or nocodazole treatment. Radiation (4 and 6 Gy)
      caused arrest in the G(2) phase of the cell cycle as well as in G(1) in Reh cells
      with an intact TP53 response. Reh cells, but not U698 and Daudi cells with
      defects in the TP53 pathway, died by apoptosis after exposure to 4 or 6 Gy
      radiation (>15% apoptotic Reh cells and <5% apoptotic U698/Daudi cells 24 h
      postirradiation). Lower doses of radiation (0.5 and 1 Gy) caused a transient
      delay in the G(2) phase of the cell cycle for the three cell lines but did not
      induce apoptosis (<5% apoptotic cells at 24 h postirradiation). Cells of all
      three cell lines died by apoptosis after exposure to 1 microg/ml nocodazole, a
      mitotic blocker that acts by inhibiting the polymerization of tubulin (>25%
      apoptotic cells after 24 h). When X irradiation with 4 or 6 Gy was performed at
      the time of addition of nocodazole to U698 and Daudi cells, X rays protected
      against the apoptosis-inducing effects of the microtubule inhibitor (<5% and 15%
      apoptotic cells, respectively, 24 h incubation). U698 and Daudi cells apparently
      have some error(s) in the signaling pathway inducing apoptosis after irradiation,
      and our results suggest that the arrest in G(2) prevents the cells from entering
      mitosis and from apoptosis in the presence of microtubule inhibitors. This arrest
      was overcome by caffeine, which caused U698 cells to enter mitosis (after
      irradiation) and become apoptotic in the presence of nocodazole (26% apoptotic
      cells, 24 h incubation). These results may have implications for the design of
      clinical multimodality protocols involving ionizing radiation for the treatment
      of cancer.

PMID- 15447043
TI  - A new approach to evaluate the total reserve of hematopoietic progenitors after
      acute irradiation.
AB  - Based on the capacity of certain hematopoietic growth factors to mobilize the
      hematopoietic progenitors from bone marrow to peripheral blood, we have
      investigated whether the number of progenitors that can be mobilized to
      peripheral blood after irradiation correlates with the radiation dose and
      reflects the total reserve of bone marrow progenitors that survive the exposure.
      In three different mouse strains, a close relationship was observed between the
      number of G-CSF mobilized progenitors and the radiation dose received by the
      animals. When G-CSF was replaced by one single injection of SD01 plus
      thrombopoietin, a similar relationship between the two parameters was observed,
      which fitted to the multitarget theoretical model. This treatment also promoted
      50% survival in mice receiving a lethal dose of 9 Gy. The estimation of the total
      number of CFU-GM progenitors in the irradiated mice also allowed us to establish
      a good relationship between the number of progenitors that were mobilized to
      peripheral blood with respect to the global reserve of surviving progenitors.
      These results suggest that the quantification of mobilized hematopoietic
      progenitors would predict the severity and reversibility of the hematopoietic
      syndrome of irradiated victims, based on direct estimations of their global
      reserve of hematopoietic progenitors and stem cells.

PMID- 15447044
TI  - Radon and thoron exposures for cave residents in Shanxi and Shaanxi provinces.
AB  - Measurements of natural radiation were carried out in cave dwellings distributed
      in the Chinese loess plateau. Those dwellings are located in Shanxi and Shaanxi
      provinces. Radon and thoron gas concentrations were measured using a passive
      integrating radon-thoron discriminative detector. Concentrations of thoron decay
      products were estimated from measurements of their deposition rates. A detector
      was placed at the center of each dwelling for 6 months and replaced with a fresh
      one for another 6 months. Measurements were conducted in 202 dwellings from
      August 2001 through August 2002. A short-term measurement was conducted during
      the observation period. In addition, gamma-ray dose rates were measured both
      indoors and outdoors with an electronic pocket dosimeter. Radioactivities in soil
      were determined by gamma-ray spectrometry with a pure germanium detector. Among
      193 dwellings, indoor radon concentrations ranged from 19 to 195 Bq m(-3) with a
      geometric mean (GM) of 57 Bq m(-3), indoor thoron concentrations ranged from 10
      to 865 Bq m(-3) with a GM of 153 Bq m(-3), and indoor equilibrium equivalent
      thoron concentrations ranged from 0.3 to 4.9 Bq m(-3) with a GM of 1.6 Bq m(-3).
      Arithmetic means of the gamma-ray dose rates were estimated to be 140 nGy h(-1)
      indoors and 110 nGy h(-1) outdoors. The present study revealed that the presence
      of thoron is not negligible for accurate radon measurements and thus that special
      attention should be paid to thoron and its decay products for dose assessment in
      such an environment. More systematic studies are necessary for a better
      understanding of thoron and its decay products.

PMID- 15447045
TI  - Effect of recent changes in atomic bomb survivor dosimetry on cancer mortality
      risk estimates.
AB  - The Radiation Effects Research Foundation has recently implemented a new
      dosimetry system, DS02, to replace the previous system, DS86. This paper assesses
      the effect of the change on risk estimates for radiation-related solid cancer and
      leukemia mortality. The changes in dose estimates were smaller than many had
      anticipated, with the primary systematic change being an increase of about 10% in
      gamma-ray estimates for both cities. In particular, an anticipated large increase
      of the neutron component in Hiroshima for low-dose survivors did not materialize.
      However, DS02 improves on DS86 in many details, including the specifics of the
      radiation released by the bombs and the effects of shielding by structures and
      terrain. The data used here extend the last reported follow-up for solid cancers
      by 3 years, with a total of 10,085 deaths, and extends the follow-up for leukemia
      by 10 years, with a total of 296 deaths. For both solid cancer and leukemia,
      estimated age-time patterns and sex difference are virtually unchanged by the
      dosimetry revision. The estimates of solid-cancer radiation risk per sievert and
      the curvilinear dose response for leukemia are both decreased by about 8% by the
      dosimetry revision, due to the increase in the gamma-ray dose estimates. The
      apparent shape of the dose response is virtually unchanged by the dosimetry
      revision, but for solid cancers, the additional 3 years of follow-up has some
      effect. In particular, there is for the first time a statistically significant
      upward curvature for solid cancer on the restricted dose range 0-2 Sv. However,
      the low-dose slope of a linear-quadratic fit to that dose range should probably
      not be relied on for risk estimation, since that is substantially smaller than
      the linear slopes on ranges 0-1 Sv, 0-0.5 Sv, and 0- 0.25 Sv. Although it was
      anticipated that the new dosimetry system might reduce some apparent dose
      overestimates for Nagasaki factory workers, this did not materialize, and factory
      workers have significantly lower risk estimates. Whether or not one makes
      allowance for this, there is no statistically significant city difference in the
      estimated cancer risk.

PMID- 15447046
TI  - PCC-FISH in skin fibroblasts for local dose assessment: biodosimetric analysis of
      a victim of the Georgian radiological accident.
AB  - We propose a new method of biodosimetry that could be applied in cases of
      localized irradiation. The approach is based on excess chromosome segments
      determination by the PCC-FISH technique in fibroblasts isolated from skin biopsy.
      Typically, 0 to 10 Gy ex vivo gamma-irradiated human skin biopsies were
      dissociated and fibroblasts were isolated and grown for several days. Cells next
      underwent PCC-FISH painting of whole chromosome 4, and the number of excess
      chromosome segments per metaphase was determined. An ex vivo reference curve
      correlating the number of excess chromosome segments per metaphase to the
      radiation dose was established and used to assess the dose delivered to the skin
      of one of the victims of the radiological accident that occurred at Lia in
      Georgia in December 2001. Specifically, the victim suffering from moist
      desquamation underwent skin excision in Hospital Percy (France). Measurement of
      excess chromosome segments per metaphase was done in fibroblasts isolated and
      grown from removed wounded skin and subsequent conversion to radiation doses was
      performed. The radiation dose map obtained was shown to be in accordance with
      clinical data and physical dosimetry as well as with conventional biodosimetry.
      These results demonstrated that PCC-FISH painting applied to skin fibroblasts may
      be a suitable technique for dose estimation. To assess its worth, this approach
      needs to be extended to future accidents involving localized radiation exposure.

PMID- 15447047
TI  - Persistence of chromatid aberrations in the cells of solid mouse tissues exposed
      to 137Cs gamma radiation.
AB  - Primary mouse ear and kidney cultures were established for determination of
      cytogenetic aberrations at short (3 days to 1 month) and long (12-23 months)
      times after exposure of their right sides to 7.5 Gy of (137)Cs gamma radiation.
      In every case, higher levels of aberrations were observed in primary cultures
      established from the irradiated tissues than in those established from the
      contralateral tissues. The most common aberrations in the contralateral tissues
      and those from nonirradiated mice were chromatid and isochromatid breaks and
      small chromatid fragments. Primary cells from irradiated tissues removed from
      animals within a month of exposure displayed a variety of unstable chromosome
      type aberrations characteristic of recent exposure to ionizing radiation
      including rings, dicentrics, double minutes, and large acentric fragments. The
      percentages of cells exhibiting chromatid breaks and small chromatid fragments
      were also markedly elevated. Although the levels of chromosome-type aberrations
      found in primary cells from irradiated tissues dropped to near background levels
      a year or more after exposure, chromatid-type aberrations remained elevated.
      These results are consistent with long-term persistence of damage in the genomes
      of ionizing radiation-exposed cells in solid tissues and the induction of genomic
      instability in vivo.

PMID- 15447048
TI  - No evidence of radiation effect on mutation rates at hypervariable minisatellite
      loci in the germ cells of atomic bomb survivors.
AB  - Human minisatellites consist of tandem arrays of short repeat sequences, and some
      are highly polymorphic in numbers of repeats among individuals. Since these loci
      mutate much more frequently than coding sequences, they make attractive markers
      for screening populations for genetic effects of mutagenic agents. Here we report
      the results of our analysis of mutations at eight hypervariable minisatellite
      loci in the offspring (61 from exposed families in 60 of which only one parent
      was exposed, and 58 from unexposed parents) of atomic bomb survivors with mean
      doses of >1 Sv. We found 44 mutations in paternal alleles and eight mutations in
      maternal alleles with no indication that the high doses of acutely applied
      radiation had caused significant genetic effects. Our finding contrasts with
      those of some other studies in which much lower radiation doses, applied
      chronically, caused significantly increased mutation rates. Possible reasons for
      this discrepancy are discussed.

PMID- 15447049
TI  - Influence of dose rate on the induction of simple and complex chromosome
      exchanges by gamma rays.
AB  - Single-color painting of whole chromosomes, or protocols in which only a few
      chromosomes are distinctively painted, will always fail to detect a proportion of
      complex exchanges because they frequently produce pseudosimple painting patterns
      that are indistinguishable from those produced by bona fide simple exchanges.
      When 24-color multi-fluor FISH (mFISH) was employed for the purpose of
      distinguishing (truly) simple from pseudosimple exchanges, it was confirmed that
      the acute low-LET radiation dose-response relationship for simple exchanges
      lacked significant upward curvature. This result has been interpreted to indicate
      that the formation of simple exchanges requires only one chromosome locus be
      damaged (e.g. broken) by radiation to initiate an exchange-not two, as classical
      cytogenetic theory maintains. Because a one-lesion mechanism implies single-track
      action, it follows that the production of simple exchanges should not be
      influenced by changes in dose rate. To examine this prediction, we irradiated
      noncycling primary human fibroblasts with graded doses of (137)Cs gamma rays at
      an acute dose rate of 1.10 Gy/min and compared, using mFISH, the yield of simple
      exchanges to that observed after exposure to the same radiation delivered at a
      chronic dose rate of 0.08 cGy/min. The shape of the dose response was found to be
      quasi-linear for both dose rates, but, counter to providing support for a one
      lesion mechanism, the yield of simple aberrations was greatly reduced by
      protracted exposure. Although chronic doses were delivered at rates low enough to
      produce damage exclusively by single-track action, this did not altogether
      eliminate the formation of complex aberrations, an analysis of which leads to the
      conclusion that a single track of low-LET radiation is capable of inducing
      complex exchanges requiring up to four proximate breaks for their formation. For
      acute exposures, the ratio of simple reciprocal translocations to simple
      dicentrics was near unity.

PMID- 15447050
TI  - Review: antibodies and antigens in immune neutropenias.

PMID- 15447051
TI  - Review: platelet immunology-similarities and differences with red cell serology.

PMID- 15447052
TI  - Flow cytometric phenotyping of platelet HPA-1a antigen: donor screening for a
      case of neonatal alloimmune thrombocytopenia due to anti-HPA-1a antibodies.
AB  - Neonatal alloimmune thrombocytopenia can effectively be treated by transfusing
      compatible platelets to the affected newborn, but typed, compatible platelets are
      not generally available. For a case of probable neonatal alloimmune
      thrombocytopenia due to anti-HPA-1a, part of the donor population of the regional
      blood bank was phenotyped to find HPA-1a-negative platelets. A flow cytometric
      technique was used, which is reliable, rapid, and relatively simple and therefore
      well suited for large-scale screening. Using this method, several HPA-1a-negative
      donors were identified, and one of them donated platelets that were successfully
      transfused to the thrombocytopenic newborn.

PMID- 15447053
TI  - Trimeresurus venom inhibition of anti-HPA-1a and anti-HPA-1b antibody binding to
      human platelets.
AB  - A solid-phase red cell adherence assay was used to demonstrate the specific
      inhibitory effect of seven species of Trimeresurus snake venom on the binding of
      HPA-1a- and HPA-1b-specific platelet antibodies. Trimeresurus venom did not
      inhibit the binding of HLA-, HPA-3a-, HPA-3b-, HPA-4a-, HPA-5a-, and HPA-5b
      specific platelet antibodies. Venom from other genera of snakes, including
      representatives from Agkistrodon, Ancistrodon, Bitis, Bothrops, Bungarus, Causus,
      Crotalus, Dendroaspis, Ecis, Micrurus, Naja, Notechis, Ophiophagus, Pseudechis,
      Sepedon (Hemachatus), and Vipera, all failed to specifically inhibit anti-HPA-1a
      and HPA-1b binding. These results may indicate that the component in Trimeresurus
      snake venom previously reported to bind to the platelet GPIIb-IIIa complex,
      inhibiting fibrinogen binding, binds close to the HPA-1a and HPA-1b epitopes.

PMID- 15447054
TI  - Review: comparing platelet compatibility to red cell compatibility protocols.

PMID- 15447055
TI  - Application of the proteolytic enzyme papain in routine platelet serology.
AB  - The use of proteolytic enzymes is well established in red cell serology. These
      enzymes modify some antigen structures and remove sialic acid from the red cell
      membrane. Enzyme-sensitive structures have also been identified on the platelet
      membrane. The effect of papain, a proteolytic enzyme used widely in red cell
      serology, on the detection of various platelet alloantibodies was examined to
      determine its usefulness in platelet serology. Antisera with the specificities
      anti-HPA-la, -2b, -3a, -4a, -5a, -5b, and -Naka were examined. HLA antibodies
      were also included. All sera were tested by a solid-phase red cell adherence
      technique in parallel with untreated platelets (UP) and platelets treated with
      papain (PP) for 15 minutes at 37 degrees C. The reactivity of anti-HPA-2b was
      eliminated and that of anti-HPA-3a was either eliminated or almost eliminated
      with PP. Antisera specific for the other alloantigens tested reacted similarly or
      more strongly with PP compared with UP. These findings were confirmed by flow
      cytometry. The reactivity of HLA antibodies with PP was generally enhanced.
      Inactivation by papain of platelet alloantigens in the HPA-2 and HPA-3 systems,
      but not in other systems, may assist in resolving mixtures of platelet
      alloantibodies. Also, detection of weak antibodies of other specificities may be
      enhanced. The use of PP may be a simple and useful serologic tool for
      investigating platelet alloantibodies.

PMID- 15447056
TI  - Detection of drug-dependent platelet antibodies by use of solid-phase red cell
      adherence techniques.
AB  - Many drugs have been reported to cause drug-dependent thrombocytopenia, either by
      the immune complex or by hapten mechanisms. Testing for the presence of these
      platelet antibodies has not been considered feasible for transfusion services
      because their presence was thought to be rare, and their detection involved
      complex and costly methods. We have developed a new technique for detection of
      these antibodies that can be performed without the need for specialized and
      expensive instrumentation. A solid-phase red cell adherence assay was used to
      detect drug-dependent platelet antibodies active by either the immune complex or
      the hapten mechanism. Three cases were evaluated for the presence of drug
      dependent platelet antibodies. Two patients presented with thrombocytopenia that
      could not be attributed to other causes. The third case was evaluated for the
      presence of drug-dependent antibodies after poor responses to platelet
      transfusions. In these three cases, discontinuation of the implicated drugs,
      i.e., porcine heparin, quinine sulfate, amoxicillin, Bactrim, and albuterol, was
      followed by a correction of thrombocytopenia or improved platelet transfusion
      response within 72 hours. This test methodology and protocol has proven very
      useful in avoiding transfusions with little likelihood of benefit, and in
      identifying drugs interfering with platelet recovery or survival. Further
      investigations with this technique may expand our knowledge of the capability of
      this technique and of the observed frequency of drug-related immunologic platelet
      destruction.

PMID- 15447057
TI  - Case report: solid-phase platelet crossmatching to support the alloimmunized
      patient.
AB  - Platelet crossmatching by a solid-phase red cell adherence assay was used to
      provide compatible platelets for two alloimmunized patients with leukemia. In
      this study, a successful platelet transfusion was defined as giving a corrected
      count increment (CCI) of >7,500 in a posttransfusion sample. For patient A, a
      total of 205 random platelet concentrates (PCs) were crossmatched. Eleven were
      considered compatible. These 11 PCs were transfused during five transfusion
      episodes. Four of the five transfusions produced CCIs of >7,500 and were
      considered successful. Individually, eight of the eleven units were considered in
      vivo compatible, and five of the eight donors of these units agreed to become
      apheresis donors. Platelets from three of these five apheresis donors gave CCIs
      of >7,500. For patient B, 1,074 random PCs were crossmatched, and 332 were
      considered compatible. These units were administered during 78 different
      transfusions. Seventy-one of these transfusion episodes resulted in CCIs of
      >7,500. In addition, 19 apheresis donors were identified by platelet
      crossmatching, and they provided platelets for 38 of 39 successful transfusions
      for Patient B. Platelet crossmatching should therefore be considered when a blood
      bank is called upon to support a refractory thrombocytopenic patient.

PMID- 15447058
TI  - Case report: a pregnant woman with immune thrombocytopenic purpura and unusual
      red cell antibodies.
AB  - Maternal immune thrombocytopenic purpura (ITP) may lead to fetal platelet
      destruction. This process is mediated by IgG platelet autoantibodies that cross
      the placenta. In this case, not only were platelet autoantibodies present, but
      red cell alloantibodies anti-E, anti-M, and anti-He were also present. Anti-E,
      present as an IgG antibody, crossed the placenta, but did not cause clinical
      problems in the E+ newborn, other than possible hyperbilirubinemia that was
      treated by phototherapy.

PMID- 15447060
TI  - ANNOTATION-Monoclonal ABO blood grouping reagents: a decade later.

PMID- 15447061
TI  - ABO discrepancy with monoclonal ABO reagents caused by a pH-dependent
      autoantibody.
AB  - ABO discrepancy was noted when a patient's unwashed saline red cell suspension
      was tested with monoclonal ABO reagents. The discrepancy was resolved when a
      washed (X 3) saline red cell suspension was used in repeat testing. The patient's
      serum contained an autoagglutinin that reacted optimally below pH 7.0. The
      discrepancy occurred when monoclonal ABO reagents, formulated at a low pH,
      lowered the pH of the reaction mixture, and autoagglutination was observed.

PMID- 15447062
TI  - The r' gene is overrepresented in hrB-negative individuals.
AB  - A screening program was implemented to identify hrB- donors. D- C+, D-C-, and D+C
      samples from African-American donors were typed with multiple examples of anti
      hrB and anti-hrB-like, and one example each of anti-V and anti-VS. Of 75 D-C+
      donors, 4 (5%) typed as hrB-, and 14 others had weak or variable expression of
      hrB. Of these 18 individuals, 15 were V-VS+, and 3 were V+VS+. No hrB- sample was
      found in 90 C- donors, 26 of whom were V+VS+, and 1 was V-VS+. A review of our
      records of 44 hrB- patients and donors studied earlier revealed that at least 12,
      and possibly as many as 30, carried r or rs. All hrB- donors found in our
      screening program had D-C+VS+ RBCs, indicating an overrepresentation of r. Our
      record review also showed that the presence of r and rs more often results in hrB
      RBCs, and that the most effective way to screen for hrB- donors is to type
      African Americans who have D-C+ RBCs.

PMID- 15447063
TI  - Detection of Lewis, P1, and some MNS blood group system antibodies by a solid
      phase assay.
AB  - Some solid phase red cell adherence (SPRCA) assays are designed to detect IgG
      antibodies to red blood cell (RBC) antigens. These assays use anti-IgG-coated red
      cells as the indicator. It is reported that most antibodies to Lea, Leb, P1, M,
      and N fail to react by solid phase (SP), presumably because they are IgM
      antibodies. Those detected are assumed to be IgG. In one year, during routine
      testing using SPRCA to screen patients for intended RBC transfusion, 28 of 59
      such examples were found to react: anti-Lea(9), -Leb(1), -M(14), -N(1), and 
      P1(3). A study was undertaken to determine if reactivity was due to crosslinking
      by IgM antibodies of antigen-positive indicator RBCs to antigen-positive reagent
      RBC monolayers, or due to detection of IgG antibodies. Antibodies were tested
      according to standard SP protocols, except where IgG-neutralized indicator RBCs
      were substituted for anti-IgG-active indicator cells. The 59 samples were
      retested with antigen-positive and antigen-negative indicator RBCs. Only 5 of 59
      reacted optimally when antigen-positive indicator cells were used: anti-Lea(2), 
      Leb(1), -M(1), and -N(1). The reactions of all antibodies were abolished when the
      anti-IgG component of the indicator was neutralized by soluble IgG. These
      findings show that detection of most Lewis, P1, M, and N antibodies by SPRCA is
      dependent on the presence of an IgG antibody in the serum.

PMID- 15447064
TI  - Correlation of monocyte monolayer assays and posttransfusion survival of Yt(a+)
      red cells in patients with anti-Yta.
AB  - Anti-Yta is an antibody to a high-frequency (99.8%) antigen and has been reported
      to have variable clinical significance. A retrospective review of monocyte
      monolayer assay (MMA) results on sera from 79 patients with anti-Yta was
      conducted to determine the reliability of this assay to predict the clinical
      significance of anti-Yta. Results of the MMA, other serological tests, and
      patient transfusion histories were analyzed. The MMA was found to be a reliable
      predictor of the clinical significance of anti-Yta when samples for analysis were
      collected at least six weeks after initial detection of the antibody. Only 18.2
      percent of those examples of anti-Yta tested appeared to be clinically
      significant.

PMID- 15447065
TI  - A simple screening method to evaluate the presence of alloantibodies with
      concomitant warm autoantibodies.
AB  - Autoantibodies are present in the serum of patients with autoimmune hemolytic
      anemia. Extensive serologic investigation is often needed to determine if
      alloantibodies are also present. To aid in the investigation, a simple method of
      serum dilution is described. The serum dilution method was compared to allogeneic
      red blood cell adsorptions in 119 cases tested over a two-year period. In 20
      percent of the cases, the same underlying alloantibodies were detected by both
      the serum dilution method and allogeneic adsorption. In 42 percent of the cases,
      all autoantibody reactivity was removed by both methods. No clinically
      significant alloantibodies were missed using serum dilution as compared to
      allogeneic adsorptions. We conclude that serum dilution is a simple, rapid way to
      initially assess for the presence of alloantibodies that co-exist with
      autoantibodies.

PMID- 15447067
TI  - Anti-Pra and ABO blood grouping discrepancies.

PMID- 15447066
TI  - A practice guideline and decision aid for blood transfusion.
AB  - An attempt was made to reduce exposure of patients to blood products by using a
      point-of-ordering decision support system and strict adherence to a practice
      guideline, by observing physician behavior in the multidisciplinary intensive
      care unit (ICU) of a tertiary-care medical center. Hemoglobin (Hg) level at the
      time of transfusion, total units of red blood cells (RBCs) per admission, units
      per patient per ICU day, fraction of patients receiving no transfusions, and
      incidence of single-unit transfusions covering 628 patients were measured. In
      Phase 1, RBC transfusion behavior was observed without intervention. In Phase 2,
      a special order form for RBCs that suggested a transfusion threshold of 8.6 g/dL
      of Hg was introduced. In Phase 3, the suggested threshold was lowered to 7.0 g/dL
      and required all transfusions that did not meet the new guideline to be
      prospectively reviewed by a transfusion medicine physician. The Hg level at
      transfusion fell from 8.5 g/dL to 8.2 g/dL (p = 0.008). The use of single-unit
      transfusions fell from 32 percent to 17 percent (p = 0.001), but there was no
      change in the number of patients receiving any blood, the total units per
      admission, or units per patient per day. In this setting, a practice guideline
      with a point-of-decision support system did not influence blood usage.
      Intermediate outcomes (such as the level of anemia at transfusion or compliance
      to a guideline) should not substitute for

PMID- 15447068
TI  - Ortho dedication.

PMID- 15447069
TI  - Identification of the Tcb allele of the Cromer blood group gene by PCR and RFLP
      analysis.
AB  - The Cromer blood group antigens reside on the complement regulatory protein,
      decay-accelerating factor (DAF). The Cromer system comprises 10 antigens, 3 of
      which are of low incidence. When an individual is homozygous for the allele
      encoding one of these low-incidence antigens, they are liable to produce an
      antibody to the antithetical high-frequency antigen if challenged by pregnancy or
      transfusion. These antibodies are often difficult to identify, because of the
      lack of readily available antigen-negative cells and typing sera. In blacks,
      about 5 percent of individuals carry the rare Tcb Cromer allele. We have shown
      that the presence of the low-incidence Tcb allele can be detected by polymerase
      chain reaction (PCR) amplification of a fragment of the gene encoding DAF,
      followed by allele-specific restriction enzyme digestion.

PMID- 15447070
TI  - Quantifying the loss of ABO antigenicity in a patient with acute myeloid leukemia
      by flow cytometric analysis.
AB  - The loss of B antigenicity from the red blood cells of a patient with acute
      myeloid leukemia is reported. The patient had normal B transferase levels, but
      had reduced levels of H transferase. Flow cytometry was used to quantify the loss
      of B antigenicity and monitor the expression of the B antigen throughout the
      progression of the disease.

PMID- 15447071
TI  - A comparison of two solid phase systems for antibody detection.
AB  - Two solid phase methods of antibody detection, Capture-R (CR) and Capture-R Ready
      Screen (RS), were compared to determine their acceptability for use in prenatal
      antibody screening. Ninety-six serum samples, screened using a saline
      antiglobulin test, were coded and tested by CR and RS at two laboratory sites
      using a blinded study design. Thirty of the samples were free of antibody, and 66
      samples contained antibody. Parallel testing was also performed in both
      laboratories on 648 prenatal samples. The sensitivity and specificity of CR,
      based on the 96 previously screened samples, was 95 percent and 90 percent,
      respectively, and the sensitivity and specificity of RS was 90 percent and 89
      percent, respectively. Antibodies detected only by CR included anti-K(1), -Ch(2),
      -Jka(1), -Lea(1), -Fya(1), -Mca(1), and -e(1). Antibodies detected only by RS
      included anti-Jka(5) and -E(1). The sensitivity and specificity of CR for the 648
      prenatal samples was 100 percent for each, while the sensitivity and specificity
      of RS was 97 percent and 100 percent, respectively. Both CR and RS are acceptable
      techniques for prenatal antibody screening.

PMID- 15447072
TI  - Analysis of the routine use of polyethylene glycol (PEG) as an enhancement
      medium.
AB  - This study compared the performance of polyethylene glycol (PEG) and low-ionic
      saline solutions (LISS) as enhancement media for routine use in a large
      transfusion service. A PEG additive solution (PEG plus LISS) was compared to a
      LISS additive (LISS plus polymers) and to an albumin-indirect antiglobulin test
      (A-IAT). Fifty serum samples containing clinically significant alloantibodies and
      fifty samples without alloantibodies were tested. Following an acute hemolytic
      transfusion reaction (HTR) involving an anti-K that was not detected with LISS
      but was retrospectively found to be reactive with PEG, an additional 151 samples
      received for antibody screening were prospectively evaluated in parallel using
      PEG and LISS. PEG detected all clinically significant antibodies in the 50
      previously tested samples, with mean reactivity scores greater than LISS or A
      IAT. In the prospective study, PEG detected 35 clinically significant antibodies
      and 10 clinically insignificant antibodies, while LISS detected only 15
      clinically significant antibodies and 33 clinically insignificant antibodies. PEG
      appears to increase detection of significant antibodies while decreasing
      detection of insignificant antibodies. PEG was therefore substituted for LISS as
      an enhancement medium and has been in routine use for 12 months, with no reported
      acute or anamnestic HTRs in 6,353 transfusions.

PMID- 15447073
TI  - Case report: anti-Cra in pregnancy.
AB  - A 39-year-old Grenadian multiparous patient presented in the 12th week of
      pregnancy. Her red cells were found to have the rare Cr(a-) (ISBT Number 202001)
      phenotype within the Cromer complex, and her serum contained anti-Cra. To date,
      anti-Cra has not been implicated in hemolytic disease of the newborn (HDN), but
      there are very few published reports on this topic. This case provided an
      excellent opportunity for study. The patient's serum showed no detectable
      functional activity in in vitro antibody-dependent, cell-mediated cytotoxicity
      assays, and no increase in the strength of the antibody during the pregnancy. The
      newborn infant showed no clinical signs of HDN, and was of normal weight. This
      case study suggests that anti- Cra is not implicated in HDN.

PMID- 15447074
TI  - LISS-dependent autoantibody with apparent anti-U specificity.
AB  - Nonspecific binding of gamma globulin and complement, resulting in falsely
      positive indirect antiglobulin tests, has occurred with use of low-ionic strength
      saline solution (LISS) reagents. These LISS-dependent antibodies have not been
      described in association with any particular disease state, nor do they have any
      apparent clinical significance. We present a LISS-dependent antibody with
      apparent autoanti-U specificity.

PMID- 15447075
TI  - The first example of anti-Gya detected in Hong Kong.
AB  - The incidence of anti-Gya is known to be extremely rare, and only a few examples
      have been reported in Japanese persons and in Caucasians. This case history
      reports the first example of anti-Gya detected in a Chinese person. The
      propositus is an 83-year-old male patient whose anti-Gya was revealed because of
      incompatibility of all units of blood tested by a saline indirect antiglobulin
      test (SIAT). Although the antibody had a titer of 512 by SIAT, 10 units of Gy(a+)
      red cells were transfused without any adverse effect.

PMID- 15447077
TI  - Vortex nucleation by collapsing bubbles in Bose-Einstein condensates.
AB  - Nucleation of vortex rings accompanies the collapse of ultrasound bubbles in
      superfluids. Using the Gross-Pitaevskii equation for a uniform condensate we
      elucidate the various stages of the collapse of a stationary spherically
      symmetric bubble and establish conditions necessary for vortex nucleation. The
      minimum radius of the stationary bubble, whose collapse leads to vortex
      nucleation, was found to be 28+/-1 healing lengths. The time after which the
      nucleation becomes possible is determined as a function of the bubble's radius.
      We show that vortex nucleation takes place in moving bubbles of even smaller
      radius if the motion makes them sufficiently oblate.

PMID- 15447078
TI  - Bohmian mechanics and quantum field theory.
AB  - We discuss a recently proposed extension of Bohmian mechanics to quantum field
      theory. For more or less any regularized quantum field theory there is a
      corresponding theory of particle motion, which, in particular, ascribes
      trajectories to the electrons or whatever sort of particles the quantum field
      theory is about. Corresponding to the nonconservation of the particle number
      operator in the quantum field theory, the theory describes explicit creation and
      annihilation events: the world lines for the particles can begin and end.

PMID- 15447079
TI  - Quasiparticle scattering by quantum phase slips in one-dimensional superfluids.
AB  - Quantum phase slips (QPS) in narrow superfluid channels generate momentum by
      unwinding the supercurrent. In a uniform Bose gas, this momentum needs to be
      absorbed by quasiparticles (phonons). We show that this requirement results in an
      additional exponential suppression of the QPS rate (compared to the rate of QPS
      induced by a sharply localized perturbation). In BCS-paired fluids, momentum can
      be transferred to fermionic quasiparticles, and we find an interesting interplay
      between quasiparticle scattering on QPS and on disorder.

PMID- 15447080
TI  - Weakly bound dimers of fermionic atoms.
AB  - We discuss the behavior of weakly bound bosonic dimers formed in a two-component
      cold Fermi gas at a large positive scattering length a for the interspecies
      interaction. We find the exact solution for the dimer-dimer elastic scattering
      and obtain a strong decrease of their collisional relaxation and decay with
      increasing a. The large ratio of the elastic to inelastic rate is promising for
      achieving Bose-Einstein condensation of the dimers and cooling the condensed gas
      to very low temperatures.

PMID- 15447081
TI  - Dilute Fermi gas in quasi-one-dimensional traps: from weakly interacting fermions
      via hard core bosons to a weakly interacting Bose gas.
AB  - We study equilibrium properties of a cold two-component Fermi gas confined in a
      quasi-one-dimensional trap of the transverse size l(perpendicular). In the dilute
      limit (nl(perpendicular)<<1, where n is the 1D density) the problem is exactly
      solvable for an arbitrary 3D fermionic scattering length aF. When
      l(perpendicular)/aF goes from -infinity to +infinity, the system successively
      passes three regimes: weakly interacting Fermi gas, hard core Bose gas, and
      weakly coupled Bose gas. The regimes are separated by two crossovers at aF
      approximately +/-nl2(perpendicular). In conclusion, we discuss experimental
      implications of these results.

PMID- 15447082
TI  - High-temperature atomic superfluidity in lattice Bose-Fermi mixtures.
AB  - We consider atomic Bose-Fermi mixtures in optical lattices and study the
      superfluidity of fermionic atoms due to s-wave pairing induced by boson-fermion
      interactions. We prove that the induced fermion-fermion coupling is always
      attractive if the boson-boson on-site interaction is repulsive, and predict the
      existence of an enhanced BEC-BCS crossover as the strength of the lattice
      potential is varied. We show that for direct on-site fermion-fermion repulsion,
      the induced attraction can give rise to superfluidity via s-wave pairing at
      striking variance with the case of pure systems of fermionic atoms with direct
      repulsive interactions.

PMID- 15447083
TI  - Universal vortex formation in rotating traps with bosons and fermions.
AB  - We show that the rotation of trapped quantum mechanical particles with a
      repulsive interaction can lead to vortex formation, irrespective of whether the
      particles are bosons or (unpaired) fermions. The exact many-particle wave
      function constitutes similar structures in both cases, implying that this vortex
      formation is indeed universal.

PMID- 15447084
TI  - Exactly solvable model of the BCS-BEC crossover.
AB  - We discuss an integrable model of interacting fermions in one dimension that
      allows a complete description of the crossover from a BCS- to a Bose-like
      superfluid. This model bridges the Gaudin-Yang model of attractive spin 1/2
      fermions to the Lieb-Liniger model of repulsive bosons. Using a geometric
      resonance in the one-dimensional scattering length, the inverse coupling constant
      varies from -infinity to +infinity while the system evolves from a BCS-like state
      through a Tonks-Girardeau gas to a weakly interacting Bose gas of dimers. We
      study the ground state energy, the elementary density and spin excitations, and
      the correlation functions. An experimental realization with cold atoms of such a
      one-dimensional BCS-BEC crossover is proposed.

PMID- 15447085
TI  - Getting the elastic scattering length by observing inelastic collisions in
      ultracold metastable helium atoms.
AB  - We report an experiment measuring simultaneously the temperature and the flux of
      ions produced by a cloud of triplet metastable helium atoms at the Bose-Einstein
      critical temperature. The onset of condensation is revealed by a sharp increase
      of the ion flux during evaporative cooling. Combining our measurements with
      previous measurements of ionization in a pure Bose-Einstein condensate, we
      extract an improved value of the scattering length a=11.3(+2.5)(-1.0) nm. The
      analysis includes corrections that take into account the effect of atomic
      interactions on the critical temperature, and thus an independent measurement of
      the scattering length would allow a new test of these calculations.

PMID- 15447086
TI  - Experimental Bell inequality violation with an atom and a photon.
AB  - We report the measurement of a Bell inequality violation with a single atom and a
      single photon prepared in a probabilistic entangled state. This is the first
      demonstration of such a violation with particles of different species. The
      entanglement characterization of this hybrid system may also be useful in quantum
      information applications.

PMID- 15447087
TI  - Scaling of decoherence in wide NMR quantum registers.
AB  - Among the most important parameters for the usefulness of quantum computers are
      the size of the quantum register and the decoherence time for the quantum
      information. The decoherence time is expected to get shorter with the number of
      correlated qubits, but experimental data are only available for small numbers of
      qubits. Solid-state nuclear magnetic resonance allows one to correlate large
      numbers of qubits (several hundred) and measure their decoherence rates. We use a
      modified magnetic dipole-dipole interaction to correlate the proton spins in a
      solid sample and observe the decay of the resulting highly correlated states. By
      systematically varying the number of correlated spins, we measure the increase of
      the decoherence rate with the size of the quantum register.

PMID- 15447088
TI  - Microscopic analysis of a thermal brownian motor.
AB  - We study a genuine Brownian motor by hard disk molecular dynamics and calculate
      analytically its properties, including its drift speed and thermal conductivity,
      from microscopic theory.

PMID- 15447089
TI  - Universality of the shear viscosity from supergravity duals.
AB  - Kovtun, Son, and Starinets proposed a bound on the shear viscosity of any fluid
      in terms of its entropy density. We argue that this bound is always saturated for
      gauge theories at large 't Hooft coupling, which admit holographically dual
      supergravity description.

PMID- 15447090
TI  - Gravitational radiation from inspiralling compact binaries completed at the third
      post-Newtonian order.
AB  - The gravitational radiation from point particle binaries is computed at the third
      post-Newtonian (3PN) approximation of general relativity. Three previously
      introduced ambiguity parameters, coming from the Hadamard self-field
      regularization of the 3PN source-type mass quadrupole moment, are consistently
      determined by means of dimensional regularization, and proved to have the values
      xi=-9871/9240, kappa=0, and zeta=-7/33. These results complete the derivation of
      the general relativistic prediction for compact binary inspiral up to 3.5PN
      order, and should be of use for searching and deciphering the signals in the
      current network of gravitational wave detectors.

PMID- 15447091
TI  - Neutrino oscillations as a probe of dark energy.
AB  - We consider a class of theories in which neutrino masses depend significantly on
      environment, as a result of interactions with the dark sector. Such theories of
      mass varying neutrinos were recently introduced to explain the origin of the
      cosmological dark energy density and why its magnitude is apparently coincidental
      with that of neutrino mass splittings. In this Letter we argue that in such
      theories neutrinos can exhibit different masses in matter and in vacuum,
      dramatically affecting neutrino oscillations. As an example of modifications to
      the standard picture, we consider simple models that may simultaneously account
      for the LSND anomaly, KamLAND, K2K, and studies of solar and atmospheric
      neutrinos, while providing motivation to continue to search for neutrino
      oscillations in short baseline experiments such as BooNE.

PMID- 15447094
TI  - Aharonov-Bohm effects in entangled molecules.
AB  - Molecules which are magnetic and conducting, if suitably entangled (e.g.,
      catenanes and knots) could exhibit Aharonov-Bohm effects which can be viewed as
      particular examples of a Berry phase. The corrections to the quantum energy
      levels reflect the entangled geometry of the molecules and, while small (they are
      proportional to the square of the fine structure constant), may be observable. We
      illustrate these corrections for a number of catenated and knotted structures.
      For couplings between the components of a catenane (link), the Aharonov-Bohm
      corrections are determined by integer-valued linking numbers. For knots, the
      Aharonov-Bohm correction is proportional to the geometric writhe of the knot.

PMID- 15447095
TI  - Inducing disallowed two-atom transitions with temporally entangled photons.
AB  - Two uncoupled two-level atoms cannot be jointly excited by classical light under
      general circumstances, due to destructive interference of excitation pathways in
      two-photon absorption. However, with temporally entangled light, two-atom
      excitation is shown possible. Photons arising from three-level cascade decay are
      intrinsically ordered in time of emission. This field correlation induces a joint
      resonance in the two-atom excitation probability via suppression of one of the
      time-ordered excitation pathways. The relative gain in two-photon absorption
      increases with the time-frequency entanglement.

PMID- 15447096
TI  - Realization of a magnetically guided atomic beam in the collisional regime.
AB  - We describe the realization of a magnetically guided beam of cold rubidium atoms,
      with a flux of 7 x 10(9) atoms/s, a temperature of 400 microK, and a mean
      velocity of 1 m/s. The rate of elastic collisions within the beam is sufficient
      to ensure thermalization. We show that the evaporation induced by a radio
      frequency wave leads to appreciable cooling and an increase in the phase space
      density. We discuss the perspectives to reach the quantum degenerate regime using
      evaporative cooling.

PMID- 15447097
TI  - Optimal control approach to suppression of radiationless transitions.
AB  - We propose a general approach for eliminating radiationless transitions in
      polyatomic molecules and illustrate it through the example of the S2-->S1
      internal conversion of pyrazine. Essential to our approach is the phenomenon of
      electronically localized eigenstates of strongly vibronically coupled
      Hamiltonians. The occurrence of such states, observed here for the first time,
      and its generality are traced to the origin of scars of periodic orbits.

PMID- 15447098
TI  - Symmetry and electronic structure of noble-metal nanoparticles and the role of
      relativity.
AB  - We present high resolution UV-photoelectron spectra of cold mass selected Cun-,
      Agn-, and Aun- with n=53-58. The observed electron density of states is not the
      expected simple electron shell structure, but is strongly influenced by electron
      lattice interactions. Only Cu55- and Ag55- exhibit highly degenerate states. This
      is a direct consequence of their icosahedral symmetry, as is confirmed by density
      functional theory calculations. Neighboring sizes exhibit perturbed electronic
      structures, as they are formed by removal or addition of atoms to the icosahedron
      and therefore have lower symmetries. Gold clusters in the same size range show
      completely different spectra with almost no degeneracy, which indicates that they
      have structures of much lower symmetry. This behavior is related to strong
      relativistic bonding effects in gold, as demonstrated by ab initio calculations
      for Au55-.

PMID- 15447099
TI  - Efficient conditional preparation of high-fidelity single photon states for fiber
      optic quantum networks.
AB  - Highly correlated photons or, accordingly, high-fidelity single-photon states are
      a prerequisite for closing detection loopholes in experimental tests of local
      realism and implementing scalable linear optical quantum computation. We
      demonstrate a parametric down-conversion source exhibiting a conditional
      detection efficiency of 51% (with corresponding preparation efficiency of 85%)
      and extraordinarily high detection rates of up to 8.5 x 10(5) coincidences/(s
      mW). We exploit a novel type-II phase matching configuration in a microstructured
      waveguide in conjunction with an ultrashort pump.

PMID- 15447100
TI  - Ghost imaging with thermal light: comparing entanglement and classical
      correlation.
AB  - We consider a scheme for coherent imaging that exploits the classical correlation
      of two beams obtained by splitting incoherent thermal radiation. This case is
      analyzed in parallel with the configuration based on two entangled beams produced
      by parametric down-conversion, and a precise formal analogy is pointed out. This
      analogy opens the possibility of using classical beams from thermal radiation for
      ghost imaging schemes in the same way as entangled beams.

PMID- 15447101
TI  - Temporal correlation vortices and topological dispersion.
AB  - Interference measurements of a polychromatic partially coherent light source
      verify the existence of a temporal correlation vortex. Topological dispersion is
      found to destabilize this singularity.

PMID- 15447093
TI  - Measurement of nonrandom event-by-event fluctuations of average transverse
      momentum in square root of (sNN)=200 GeV Au+Au and p+p collisions.
AB  - Event-by-event fluctuations of the average transverse momentum of produced
      particles near midrapidity have been measured by the PHENIX Collaboration in
      square root of (sNN)=200 GeV Au+Au, and p+p collisions at the Relativistic Heavy
      Ion Collider. The fluctuations are observed to be in excess of the expectation
      for statistically independent particle emission for all centralities. The excess
      fluctuations exhibit a dependence on both the centrality of the collision and on
      the pT range over which the average is calculated. Both the centrality and pT
      dependence can be well reproduced by a simulation of random particle production
      with the addition of contributions from hard-scattering processes.

PMID- 15447102
TI  - Nonequivalence of spatial shifts and Wigner delays at interfaces.
AB  - We isolate spatial shifts and Wigner delays for reflection at the same interface
      and demonstrate that they can carry different information. The spatial shifts
      associated with Wood anomalies on gratings can be either positive or negative,
      while the corresponding delays are both positive. In the standard case of total
      reflection at a glass-air interface, a differential two-photon absorption
      correlation technique allows us to measure for the first time a delay of up to 35
      fs in agreement with the associated 10.5 microm spatial shift. The method also
      allows us to isolate giant Wigner delays. The existence of similar delays in
      different areas of physics is discussed.

PMID- 15447103
TI  - Nonlinear optical beam interactions in waveguide arrays.
AB  - We report our investigation of Kerr nonlinear beam interactions in discrete
      systems. The influence of power and the relative phase between two Gaussian
      shaped beams was investigated in detail by performing numerical simulations of
      the discrete nonlinear Schrodinger equation and comparing the results with
      experiments done in AlGaAs waveguide arrays. Good agreement between theory and
      experiment was obtained.

PMID- 15447104
TI  - Rotary solitons in bessel optical lattices.
AB  - We introduce solitons supported by Bessel photonic lattices in cubic nonlinear
      media. We show that the cylindrical geometry of the lattice, with several
      concentric rings, affords unique soliton properties and dynamics. In particular,
      in addition to the lowest-order solitons trapped in the center of the lattice, we
      find soliton families trapped at different lattice rings. Such solitons can be
      set into controlled rotation inside each ring, thus featuring novel types of in
      ring and inter-ring soliton interactions.

PMID- 15447105
TI  - Power-law slip profile of the moving contact line in two-phase immiscible flows.
AB  - Large-scale molecular dynamics (MD) simulations on two-phase immiscible flows
      show that, associated with the moving contact line, there is a very large 1/x
      partial-slip region where x denotes the distance from the contact line. This
      power-law partial-slip region is verified in large-scale adaptive continuum
      calculations based on a local, continuum hydrodynamic formulation, which has
      proved successful in reproducing MD results at the nanoscale. Both MD simulations
      and numerical solutions of continuum equations indicate the existence of a
      universal slip profile in the Stokes-flow regime.

PMID- 15447106
TI  - Hydrodynamic theory of forced dewetting.
AB  - A prototypical problem in the study of wetting phenomena is that of a solid
      plunging into or being withdrawn from a liquid bath. In the latter, dewetting
      case, a critical speed exists above which a three-phase contact line is no longer
      sustainable and the solid can no longer remain dry. Instead, a liquid film is
      being deposited on the solid. Demonstrating this transition from a dry to a
      wetted solid to be of hydrodynamic origin, we provide the first theoretical
      explanation of a classical prediction due to Derjaguin and Levi: instability
      occurs when the outer, static meniscus approaches the shape corresponding to a
      perfectly wetting fluid. Our analysis investigates the conditions under which the
      highly curved contact line region can be matched to the static profile far away
      from it.

PMID- 15447107
TI  - A model describing stable coherent synchrotron radiation in storage rings.
AB  - We present a model describing high power stable broadband coherent synchrotron
      radiation (CSR) in the terahertz frequency region in an electron storage ring.
      The model includes distortion of bunch shape from the synchrotron radiation (SR),
      which enhances higher frequency coherent emission, and limits to stable emission
      due to an instability excited by the SR wakefield. It gives a quantitative
      explanation of several features of the recent observations of CSR at the BESSY II
      storage ring. We also use this model to optimize the performance of a source for
      stable CSR emission.

PMID- 15447108
TI  - How to realize uniform three-dimensional ellipsoidal electron bunches.
AB  - Uniform three-dimensional ellipsoidal distributions of charge are the ultimate
      goal in charged particle accelerator physics because of their linear internal
      force fields. Such bunches remain ellipsoidal with perfectly linear position
      momentum phase space correlations in any linear transport system. We present a
      method, based on photoemission by radially shaped femtosecond laser pulses, to
      actually produce such bunches.

PMID- 15447109
TI  - Observation of superradiant amplification of ultrashort laser pulses in a plasma.
AB  - We demonstrate the amplification of a femtosecond signal pulse in an underdense
      plasma by a novel mechanism called superradiant amplification. The pulse is
      amplified by a counterpropagating few picosecond long pump pulse. In the
      superradiant regime, the ponderomotive forces exceed the electrostatic forces and
      arrange the plasma electrons to reflect the pump light into the signal pulse. We
      found a significant amplification in energy and intensity. The time structure of
      the amplified signal pulse carries intrinsic features of the superradiant regime.
      Sub-10-fs pulses of petawatt power appear feasible.

PMID- 15447110
TI  - Coherent shear phonon generation and detection with ultrashort optical pulses.
AB  - Using an optical technique we generate and detect picosecond shear and quasishear
      coherent acoustic phonon pulses in the time domain. Thermoelastic and
      piezoelectric generation are directly achieved by breaking the sample lateral
      symmetry using crystalline anisotropy. We demonstrate efficient detection in
      isotropic and anisotropic media with various optical incidence geometries.

PMID- 15447092
TI  - Search for B0 decays to invisible final states and to nunugamma.
AB  - We establish upper limits on branching fractions for B0 decays to final states
      where the decay products are purely invisible (i.e., no observable final state
      particles) and for B0 decays to nunugamma. Within the standard model, these
      decays have branching fractions that are below current experimental sensitivity,
      but various models of physics beyond the standard model predict significant
      contributions from these channels. Using 88.5 x 10(6) BB pairs collected at the
      Upsilon(4S) resonance by the BABAR experiment at the PEP-II e(+)e- storage ring
      at the Stanford Linear Accelerator Center, we establish upper limits at the 90%
      confidence level of 22 x 10(-5) for the branching fraction of B0-->invisible and
      4.7 x 10(-5) for the branching fraction of B0-->nunugamma.

PMID- 15447111
TI  - Experimental evidence for a high-pressure isostructural phase transition in
      osmium.
AB  - We have measured the isothermal equation of state (EOS) of osmium to 75 GPa under
      hydrostatic conditions at room temperature using angle-dispersive x-ray
      diffraction. A least-squares fit of this data using a third-order Birch-Murnaghan
      EOS yields an isothermal bulk modulus K0=411+/-6 GPa, showing osmium is more
      compressible than diamond. Most importantly, we have documented an anomaly in the
      compressibility around 25 GPa associated with a discontinuity in the first
      pressure derivative of the c/a ratio. This discontinuity plausibly arises from
      the collapse of the small hole-ellipsoid in the Fermi surface near the L point.

PMID- 15447112
TI  - Silicon monoxide clusters: the favorable precursors for forming silicon
      nanostructures.
AB  - Using density-functional calculations, we show that the energetically favorable
      configurations of silicon monoxide clusters (SiO)n for n> or =5 facilitate the
      nucleation and growth of silicon nanostructures as the clusters contain sp3
      silicon cores surrounded by silicon oxide sheaths. The frontier orbitals of
      (SiO)n clusters are localized to a significant degree on the silicon atoms on the
      surface, providing high reactivity for further stacking with other clusters. The
      oxygen atoms in the formed larger clusters prefer to migrate from the centers to
      the exterior surfaces, leading to the growth of sp3 silicon cores.

PMID- 15447113
TI  - Unusual freezing and melting of gallium encapsulated in carbon nanotubes.
AB  - The freezing and melting behavior of gallium (Ga) encapsulated in carbon
      nanotubes was investigated through in situ observation in a transmission electron
      microscope. It is shown that Ga remains liquid up to -80 degrees C when
      encapsulated in carbon nanotubes. Results of detailed electron diffraction
      analysis show that the encapsulated Ga can crystallize in either beta phase or
      gamma phase rather than the common alpha phase upon freezing. Both beta-Ga and
      gamma-Ga melt at around -20 degrees C. While this is very close to the melting
      point of bulk beta-Ga (-16 degrees C), it is considerably higher than that of
      bulk gamma-Ga (-35.6 degrees C). It was observed that upon solidification, Ga has
      its unique crystallographic orientation relative to the host carbon nanotube.

PMID- 15447114
TI  - Subcritical statistics in rupture of fibrous materials: experiments and model.
AB  - We study experimentally the slow growth of a single crack in a fibrous material
      and observe stepwise growth dynamics. We model the material as a lattice where
      the crack is pinned by elastic traps and grows due to thermally activated stress
      fluctuations. In agreement with experimental data we find that the distribution
      of step sizes follows subcritical point statistics with a power law (exponent
      3/2) and a stress-dependent exponential cutoff diverging at the critical rupture
      threshold.

PMID- 15447115
TI  - Discontinuous tangential stress in double wall carbon nanotubes.
AB  - We have examined the stability of double wall carbon nanotubes under hydrostatic
      pressures up to 10 GPa. The tangential optical phonon mode observed by inelastic
      light scattering is sensitive to the in-plane stress and splits into a
      contribution associated with the external and internal tube. While the pressure
      coefficient from the external tube is the same as in single wall carbon
      nanotubes, the pressure coefficient from the internal tube is found to be 45%
      smaller. The phonon band from the external tube broadens considerably with
      applied pressure in contrast with the phonon band of the internal tube which
      stays constant. These pressure dependent phonon shifts of the external and
      internal tubes and the contrasting phonon line broadening are explained by the
      elastic continuum shell model which takes into account both the continuous radial
      and discontinuous tangential stress components.

PMID- 15447116
TI  - First-principles prediction of a decagonal quasicrystal containing boron.
AB  - We interpret experimentally known B-Mg-Ru crystals as quasicrystal approximants
      whose deterministic decoration of tiles by atoms can be extended
      quasiperiodically. Experimentally observed disorder corresponds to phason
      fluctuations. First-principles total energy calculations find many distinct
      tilings close to stability and suggest a phase transition from a crystalline
      state at low temperatures to a high temperature state characterized by tile
      fluctuations. We predict B38Mg17Ru45 forms a metastable decagonal quasicrystal
      that may be thermodynamically stable at high temperatures.

PMID- 15447117
TI  - Superlubricity: a paradox about confined fluids resolved.
AB  - Using the method of Frantz and Salmeron to cleave mica [Tribol. Lett. 5, 151
      (1998)]] we investigate alkane fluids in a surface forces apparatus and confirm
      several predictions of molecular dynamics (MD) simulation. An oscillatory force
      distance profile is observed for the methyl-branched alkane, squalane. Boundary
      slip is inferred from the frictional sliding of molecularly thin fluids and also
      from the hydrodynamic flow of thicker films. These findings resolve the paradox
      that prior experiments disagreed with these aspects of MD predictions, and
      demonstrate that exceptionally low energy dissipation is possible when fluids
      move past solid surfaces that are sufficiently smooth.

PMID- 15447118
TI  - Lifetimes of excited electrons in Fe and Ni: first-principles GW and the T-matrix
      theory.
AB  - We present the results of an ab initio calculation of excited electron lifetimes
      in ferromagnetic materials which incorporates non-spin-flip and spin-flip
      processes within GW and T-matrix approaches. The method we develop is applied to
      low-energy electron excitations in Fe and Ni. It is found that the spin-wave
      generation in Fe essentially reduces the lifetimes of the spin-minority d states
      whereas the free-electron-like spin-minority states and all the spin-majority
      states are affected much less. The influence of spin-flip scattering on the
      lifetimes in Ni appears to be weak. The T-matrix non-spin-flip processes are
      important for the lifetimes of excited spin-minority states.

PMID- 15447119
TI  - Gruneisen ratio divergence at the quantum critical point in CeCu(6-x)Agx.
AB  - The heavy-fermion system CeCu6-xAgx is studied at its antiferromagnetic quantum
      critical point, xc=0.2, by low-temperature (T> or =50 mK) specific heat, C(T),
      and volume thermal expansion, beta(T), measurements. Whereas C/T proportional to
      log((T0/T) would be compatible with the predictions of the itinerant spin-density
      wave (SDW) theory for two-dimensional critical spin fluctuations, beta(T)/T and
      the Gruneisen ratio, Gamma(T) proportional to beta/C, diverge much weaker than
      expected, in strong contrast to this model. Both C and beta, plotted as a
      function of the reduced temperature t=T/T0 with T0=4.6 K, are similar to what was
      observed for YbRh2(Si(0.95)Ge(0.05))2 (T0=23.3 K), indicating a striking
      discrepancy to the SDW prediction in both systems.

PMID- 15447120
TI  - First-principles theory of intermediate-valence f-electron systems.
AB  - We propose a first-principles based method for calculating the electronic
      structure and total energy of solids in an intermediate-valence configuration.
      The method takes into account correlation effects (d-f Coulomb interaction) and
      many-body renormalization of the effective hybridization parameter of the f
      system. As an example, the formation of a pressure-induced intermediate-valence
      state in Yb is considered and its electronic structure and equation of state are
      calculated and compared to experimental data. The agreement is found to be
      excellent for both properties, and we argue that the developed method, which
      applies to any element or compound, provides for the first time a quantitative
      theoretical treatment of intermediate-valence materials.

PMID- 15447121
TI  - Electronic and transport properties of artificial gold chains.
AB  - We study the electronic and transport properties of artificial Au atomic chains
      on a NiAl(110) surface template using state-of-the-art first principles
      calculations. Au chains display remarkable one-dimensional electronic properties
      that can be tuned by the selective adsorption of small molecules: a single CO
      group is shown to modulate the electronic wave functions, acting as a "chemical
      scissor" along the chain, to strongly modify the coherent transport properties of
      the system, and to help design one-dimensional nanodevices through artificial
      profiling of energy barriers.

PMID- 15447122
TI  - Antibunched photons emitted by a quantum point contact out of equilibrium.
AB  - Motivated by the experimental search for "GHz nonclassical light," we identify
      the conditions under which current fluctuations in a narrow constriction generate
      sub-Poissonian radiation. Antibunched electrons generically produce bunched
      photons, because the same photon mode can be populated by electrons decaying
      independently from a range of initial energies. Photon antibunching becomes
      possible at frequencies close to the applied voltage V x e/variant Planck's over
      2pi, when the initial energy range of a decaying electron is restricted. The
      condition for photon antibunching in a narrow frequency interval below eV/variant
      Planck's over 2pi reads [SigmanTn(1-Tn)]2<2Sigman[Tn(1-Tn)]2, with Tn an
      eigenvalue of the transmission matrix. This condition is satisfied in a quantum
      point contact, where only a single Tn differs from 0 or 1. The photon statistics
      is then a superposition of binomial distributions.

PMID- 15447123
TI  - Absorption spectrum around nu=1: evidence for a small-size Skyrmion.
AB  - We measure the absorption spectrum of a two-dimensional electron system (2DES) in
      a GaAs quantum well in the presence of a perpendicular magnetic field. We focus
      on the absorption spectrum into the lowest Landau level around nu=1. We find that
      the spectrum consists of bound electron-hole complexes, trionlike and
      excitonlike. We show that their oscillator strength is a powerful probe of the
      2DES spatial correlations. We find that near nu=1 the 2DES ground state consists
      of Skyrmions of small size (a few magnetic lengths).

PMID- 15447124
TI  - Optical probing of spin polarization of electrons in quantum dot edge channels.
AB  - We propose an optical method for the investigation of the quantum dot edge
      channels by utilizing circularly polarized photoluminescence in the integer
      quantum-Hall-effect regime. One of the advantages of our method is that the
      degree of the spin-polarization of the electrons in the inner- and outer
      compressible liquids can be probed separately. The observed polarized
      photoluminescence spectra can be explained by the calculated electron spin
      dependent optical transition probabilities based on the local-spin density
      approximation.

PMID- 15447125
TI  - Is the quantum Hall effect influenced by the gravitational field?
AB  - Most of the experiments on the quantum Hall effect (QHE) were made at
      approximately the same height above sea level. A future international comparison
      will determine whether the gravitational field g(x) influences the QHE. In the
      realm of (1+2)-dimensional phenomenological macroscopic electrodynamics, the Ohm
      Hall law is metric independent ("topological"). This suggests that it does not
      couple to g(x). We corroborate this result by a microscopic calculation of the
      Hall conductance in the presence of a post-Newtonian gravitational field.

PMID- 15447126
TI  - Transition from a Tomonaga-Luttinger liquid to a fermi liquid in potassium
      intercalated bundles of single-wall carbon nanotubes.
AB  - We report on the first direct observation of a transition from a Tomonaga
      Luttinger liquid to a Fermi-liquid behavior in potassium-intercalated mats of
      single-wall carbon nanotubes. Using high resolution photoemission spectroscopy,
      an analysis of the spectral shape near the Fermi level reveals a Tomonaga
      Luttinger liquid power law scaling in the density of states for the pristine
      sample and for low dopant concentration. As soon as the doping is high enough to
      achieve a filling of the conduction bands of the semiconducting tubes, a distinct
      transition to metallic single-wall carbon nanotube bundles with the scaling
      behavior of a normal Fermi liquid occurs.

PMID- 15447127
TI  - Topological Hall effect and Berry phase in magnetic nanostructures.
AB  - We discuss the anomalous Hall effect in a two-dimensional electron gas subject to
      a spatially varying magnetization. This topological Hall effect does not require
      any spin-orbit coupling and arises solely from Berry phase acquired by an
      electron moving in a smoothly varying magnetization. We propose an experiment
      with a structure containing 2D electrons or holes of diluted magnetic
      semiconductor subject to the stray field of a lattice of magnetic nanocylinders.
      The striking behavior predicted for such a system (of which all relevant
      parameters are well known) allows one to observe unambiguously the topological
      Hall effect and to distinguish it from other mechanisms.

PMID- 15447128
TI  - Evidence for multiband superconductivity in the heavy Fermion compound UNi2Al3.
AB  - Epitaxial thin films of the heavy fermion superconductor UNi2Al3 with
      Tc(max)=0.98 K were investigated. The transition temperature Tc depends on the
      current direction which can be related to superconducting gaps opening at
      different temperatures. Also the influence of the magnetic ordering at TN
      approximately 5 K on R(T) is strongly anisotropic, indicating different coupling
      between the magnetic moments and itinerant charge carriers on the multisheeted
      Fermi surface. The upper critical field Hc2(T) suggests an unconventional spin
      singlet superconducting state.

PMID- 15447129
TI  - Vortex nanoliquid in high-temperature superconductors.
AB  - Using a differential magneto-optical technique to visualize the flow of transport
      currents, we reveal a new delocalization line within the reversible vortex liquid
      region in the presence of a low density of columnar defects. This line separates
      a homogeneous vortex liquid, in which all the vortices are delocalized, from a
      heterogeneous "nanoliquid" phase, in which interconnected nanodroplets of vortex
      liquid are caged in the pores of a solid skeleton formed by vortices pinned on
      columnar defects. The nanoliquid phase displays high correlation along the
      columnar defects but no transverse critical current.

PMID- 15447130
TI  - Fluctuations and vortex-pattern ordering in the fully frustrated XY model on a
      honeycomb lattice.
AB  - The accidental degeneracy of various ground states of a fully frustrated XY model
      with a honeycomb lattice is shown to survive even when the free energy of the
      harmonic fluctuations is taken into account. The reason for that consists in the
      existence of a hidden gauge symmetry between the Hamiltonians describing the
      harmonic fluctuations in all these ground states. A particular vortex pattern is
      selected only when anharmonic fluctuations are taken into account. However, the
      observation of vortex ordering requires relatively large system size L>>Lc > or
      approximately equal to 10(5).

PMID- 15447131
TI  - Imaging nanoscale electronic inhomogeneity in the lightly doped Mott insulator
      Ca(2-x)NaxCuO2Cl2.
AB  - The spatial variation of electronic states was imaged in the lightly doped Mott
      insulator Ca(2-x)NaxCuO2Cl2 using scanning tunneling microscopy or spectroscopy.
      We observed nanoscale domains with a high local density of states within an
      insulating background. The observed domains have a characteristic length scale of
      2 nm (approximately 4-5a, a: lattice constant) with preferred orientations along
      the tetragonal [100] direction. We argue that such spatially inhomogeneous
      electronic states are inherent to slightly doped Mott insulators and play an
      important role for the insulator to metal transition.

PMID- 15447132
TI  - Nesting, spin fluctuations, and odd-gap superconductivity in NaxCoO2.yH2O.
AB  - We calculated the one-electron susceptibility of hydrated NaxCoO2 and find strong
      nesting, involving about 70% of all electrons at the Fermi level and nearly
      commensurate with a 2 x 2 superstructure. This nesting creates a tendency to a
      charge density wave compatible with the charge order often seen at x
      approximately 0.5 and usually ascribed to electrostatic repulsion of Na ions. In
      the spin channel, it leads to strong spin fluctuations, which should be important
      for superconductivity. The state most compatible with this nesting structure is
      an odd-gap triplet s-wave state.

PMID- 15447133
TI  - Exotic versus conventional scaling and universality in a disordered bilayer
      quantum heisenberg antiferromagnet.
AB  - We present Monte Carlo simulations of a two-dimensional bilayer quantum
      Heisenberg antiferromagnet with random dimer dilution. In contrast with exotic
      scaling scenarios found in other random quantum systems, the quantum phase
      transition in this system is characterized by a finite-disorder fixed point with
      power-law scaling. After accounting for corrections to scaling, with a leading
      irrelevant exponent of omega approximately 0.48, we find universal critical
      exponents z=1.310(6) and nu=1.16(3). We discuss the consequences of these
      findings and suggest new experiments.

PMID- 15447134
TI  - Direct observation of large electronic domains with memory effect in doped
      manganites.
AB  - We use a spatially resolved, direct spectroscopic probe for electronic structure
      with an additional sensitivity to chemical compositions to investigate high
      quality single crystal samples of La(1/4)Pr(3/8)Ca(3/8)MnO3, establishing the
      formation of distinct insulating domains embedded in the metallic host at low
      temperatures. These domains are found to be at least an order of magnitude larger
      in size compared to previous estimates and exhibit memory effects on temperature
      cycling in the absence of any perceptible chemical inhomogeneity, suggesting long
      range strains as the probable origin.

PMID- 15447135
TI  - Symmetry driven irreversibilities at ferromagnetic-antiferromagnetic interfaces.
AB  - The coupling between a ferromagnet and an antiferromagnet can establish a
      directional anisotropy called exchange bias. In many systems this exchange bias
      is reduced upon subsequent field cycling, which is referred to as training
      effects. Numerical simulations of a simple coherent rotation model suggest that
      the symmetry of the anisotropy in the antiferromagnet is crucial for the
      understanding of training effects in exchange bias systems. Namely, the existence
      of multiple antiferromagnetic easy anisotropy axes can initially stabilize a
      noncollinear arrangement of the antiferromagnetic spins, which relaxes into a
      collinear arrangement after the first magnetization reversal of the ferromagnet.

PMID- 15447136
TI  - Applicability of the spin-orbit sum rule for the actinide 5f states.
AB  - The branching ratio of core-valence transitions in electron energy-loss
      spectroscopy and x-ray absorption spectroscopy is linearly related to the
      expectation value of the spin-orbit operator of the valence states. Here, we
      analyze the branching ratio of the N(4,5) edges in the actinides and find that
      the spin-orbit sum rule gives an accurate result without the need to include the
      core-valence interactions. The branching ratio is not only useful to study the
      variations in the 5f spin-orbit interaction, it also allows us to constrain the
      5f count for given angular-momentum coupling conditions.

PMID- 15447137
TI  - Nonlinear optical spectroscopy of suboxides at oxidized Si(111) interfaces.
AB  - Native oxidation of the Si(111)(1 x 1)H surface causes the appearance and
      disappearance of second-harmonic generation (SHG) resonances related to specific
      bonding configurations of Si atoms at the interface. Resonances at 3.52 eV two
      photon energy observed in p-polarized SHG spectra are indicative of a Si suboxide
      configuration present in a partially oxidized Si surface bilayer. Similar
      resonances are observed in spectra of thermally oxidized Si(111) and point to
      Si2+ suboxide states at the buried interface.

PMID- 15447138
TI  - Formation of solid-state excitons in ultrathin crystalline films of PTCDA: from
      single molecules to molecular stacks.
AB  - We directly follow the evolution of the absorption spectrum from a single
      molecule to a dimer and further to a one-dimensional molecular stack: We
      determine the optical absorption properties of ordered monolayer to multilayer
      films of PTCDA (3,4,9,10-perylenetetracarboxylic dianhydride) on muscovite
      mica(0001) surfaces by in situ differential reflectance spectroscopy. The data
      clearly show the transition from the single molecule to a dimer spectrum,
      followed by the exciton delocalization to a molecular crystal exciton. The
      accompanying spectral shifts compare favorably with recent model concepts.

PMID- 15447139
TI  - Memory of multiple aging stages above the freezing temperature in the Relaxor
      ferroelectric PLZT.
AB  - The dynamic dielectric susceptibility and the elastic compliance of the relaxor
      ferroelectric lanthanum lead zirconate titanate (PLZT) 9/65/35 have been measured
      under different cooling and heating protocols in order to study aging and memory.
      The memory of multiple aging stages at different temperatures has been found
      (several dips in the susceptibility curves on heating), as in spin glass systems
      below the glass transition. Remarkably, in PLZT the memory of several aging
      stages is retained also above the freezing temperature deduced from the dynamic
      susceptibilities. The results are discussed in light of the existing models of
      aging and memory in spin and dipolar glasses.

PMID- 15447140
TI  - Spin accumulation in forward-biased MnAs/GaAs Schottky diodes.
AB  - We describe a new means for all-electrical generation of spin polarization in
      semiconductors. In contrast with spin injection of electrons by tunneling through
      a reverse-biased Schottky barrier, we observe accumulation at the metal
      semiconductor interface of forward-biased ferromagnetic Schottky diodes, which is
      consistent with a theory of spin-dependent reflection off the interface.
      Spatiotemporal Kerr microscopy is used to image the electron spin and the
      resulting dynamic nuclear polarization that arises from the nonequilibrium
      carrier polarization.

PMID- 15447141
TI  - Fast sound in expanded fluid Hg accompanying the metal-nonmetal transition.
AB  - The dynamic structure factor S(Q,omega) of expanded fluid Hg has been measured up
      to the metal-nonmetal transition region at 9.0 g cm(-3) (1723 K and 1940 bars)
      using high-resolution inelastic x-ray scattering, at momentum transfers, Q, from
      0.2 to 4.8 A(-1). Analysis in the framework of generalized hydrodynamics reveals
      that the frequencies of the collective excitations increase faster with Q than
      estimated from the macroscopic speed of sound. The effective sound velocity at
      9.0 g cm(-3) estimated from the dispersion relation is triple the ultrasonic
      sound velocity. The present result suggests the existence of fast sound in
      expanded fluid Hg accompanying the metal-nonmetal transition.

PMID- 15447142
TI  - Criticality in the relaxation phase of a spontaneously contracting atria isolated
      from a frog's heart.
AB  - We investigate the spontaneous contraction generated by the atria of a frog's
      heart isolated in a physiological solution. In the relaxation phase, the recorded
      time series for two different sampling rates possesses an intermittent component
      similar to the dynamics of the order parameter's fluctuations of a thermal
      critical system belonging to the mean field universality class. This behavior is
      not visible through conventional analysis in the frequency space due to the
      presence of Brownian noise dominating the corresponding power spectrum.

PMID- 15447143
TI  - Commonality of elastic relaxation times in biofilms.
AB  - Biofilms, sticky conglomerations of microorganisms and extracellular polymers,
      are among the Earth's most common life forms. One component for their survival is
      an ability to withstand external mechanical stress. Measurements indicate that
      biofilm elastic relaxation times are approximately the same (about 18 min) over a
      wide sample of biofilms though other material properties vary significantly. A
      possible survival significance of this time scale is that it is the shortest
      period over which a biofilm can mount a phenotypic response to transient
      mechanical stress.

PMID- 15447144
TI  - Self-concentration and large-scale coherence in bacterial dynamics.
AB  - Suspensions of aerobic bacteria often develop flows from the interplay of
      chemotaxis and buoyancy. We find in sessile drops that flows related to those in
      the Boycott effect of sedimentation carry bioconvective plumes down the slanted
      meniscus and concentrate cells at the drop edge, while in pendant drops such self
      concentration occurs at the bottom. On scales much larger than a cell,
      concentrated regions in both geometries exhibit transient, reconstituting, high
      speed jets straddled by vortex streets. A mechanism for large-scale coherence is
      proposed based on hydrodynamic interactions between swimming cells.

PMID- 15447145
TI  - Coarse-grained model of entropic allostery.
AB  - Many signaling functions in molecular biology require proteins to bind to
      substrates such as DNA in response to environmental signals such as the
      simultaneous binding to a small molecule. Examples are repressor proteins which
      may transmit information via a conformational change in response to the ligand
      binding. An alternative entropic mechanism of "allostery" suggests that the
      inducer ligand changes the intramolecular vibrational entropy, not just the mean
      static structure. We present a quantitative, coarse-grained model of entropic
      allostery, which suggests design rules for internal cohesive potentials in
      proteins employing this effect. It also addresses the issue of how the signal
      information to bind or unbind is transmitted through the protein. The model may
      be applicable to a wide range of repressors and also to signaling in trans
      membrane proteins.

PMID- 15447146
TI  - Ecosystem engineers: from pattern formation to habitat creation.
AB  - Habitat and species richness in drylands are affected by the dynamics of a few
      key species, termed "ecosystem engineers." These species modulate the landscape
      and redistribute the water resources so as to allow the introduction of other
      species. A mathematical model is developed for a pair of ecosystem engineers
      commonly found in drylands: plants forming vegetation patterns and cyanobacteria
      forming soil crusts. The model highlights conditions for habitat creation and for
      high habitat richness, and suggests a novel mechanism for species loss events as
      a result of environmental changes.

PMID- 15447147
TI  - Hydrodynamics of nanoscopic tubulin rings in dilute solutions.
AB  - We combine fluorescence correlation spectroscopy and sedimentation velocity
      measurements to probe the hydrodynamic behavior of tubulin dimers and nanoscopic
      tubulin rings. The rings are rigid, have circular geometry, and are monodisperse
      in size. We use the high-precision ratio of the sedimentation coefficients and
      that of the translational diffusion coefficients to validate theories for
      calculating the hydrodynamic properties of supramolecular structures.

PMID- 15447148
TI  - Emergence of prime numbers as the result of evolutionary strategy.
AB  - We investigate by means of a simple theoretical model the emergence of prime
      numbers as life cycles, as those seen for some species of cicadas. The cicadas,
      more precisely the Magicicadas, spend most of their lives below the ground and
      then emerge and die in a short period of time. The Magicicadas display an
      uncommon behavior: their emergence is synchronized and these periods are usually
      prime numbers. In the current work, we develop a spatially extended model at
      which preys and predators coexist and can change their evolutionary dynamics
      through the occurrence of mutations. We verified that prime numbers as life
      cycles emerge as a result of the evolution of the population. Our results seem to
      be a first step in order to prove that the development of such strategy is
      selectively advantageous, especially for those organisms that are highly
      vulnerable to attacks of predators.

PMID- 15447149
TI  - Anisotropic thermal conduction in a polymer liquid subjected to shear flow.
AB  - Flow-induced anisotropic thermal conduction in a polymer liquid is studied using
      force Rayleigh scattering. Time-dependent measurements of the complete thermal
      diffusivity tensor, which includes one off-diagonal and three diagonal
      components, are reported on an entangled polymer melt subjected to a uniform
      shear deformation. These data, in conjunction with mechanical measurements of the
      stress, provide the first direct evidence that the thermal conductivity tensor
      and the stress tensor are linearly related in a deformed polymer liquid.

PMID- 15447150
TI  - Transverse instability of line defects of period-2 spiral waves.
AB  - Spiral waves that arise in period-2 oscillatory media extended in space
      generically bear "line defects" along which the local kinetics exhibits a period
      1 oscillation. Locally, these defect structures can be viewed as a front
      separating two period-2 oscillatory domains oscillating 2pi out of phase. Here we
      show that their shape can become sinusoidal with a transverse instability as in
      bistable fronts. This instability eventually leads to a line-defect filled
      spatiotemporal chaotic state having erratic proliferations, annihilations, and
      regenerations of line defects. The same sequence of phenomena is observed in a
      model reaction-diffusion system as well as in an experimental system.

PMID- 15447151
TI  - Running pulses of complex shape in a reaction-diffusion model.
AB  - In a one-dimensional reaction-diffusion model of an active medium, stable steady
      state wave pulses of a new type are described. They are called multihumped
      because their waveforms contain several maxima of similar size. Presumably, the
      multihumped pulses arise via a bifurcation at which an unstable trigger wave
      disappears. The parameter governing this bifurcation is the diffusion coefficient
      for the model inhibitor. The model is analyzed by varying this parameter to
      determine the conditions for the emergence of multihumped pulses. The results of
      this analysis show how their waveform and dynamics of excitation depend on the
      inhibitor diffusion coefficient.

PMID- 15447152
TI  - Self-stabilized fractality of seacoasts through damped erosion.
AB  - Erosion of rocky coasts spontaneously creates irregular seashores. But the
      geometrical irregularity, in turn, damps the sea waves, decreasing the average
      wave amplitude. There may then exist a mutual self-stabilization of the wave
      amplitude together with the irregular morphology of the coast. A simple model of
      such stabilization is studied. It leads, through a complex dynamics of the earth
      sea interface, to the appearance of a stationary fractal seacoast with a
      dimension close to 4/3. Fractal geometry here plays the role of a morphological
      attractor directly related to percolation geometry.

PMID- 15447153
TI  - Cascade control and defense in complex networks.
AB  - Complex networks with a heterogeneous distribution of loads may undergo a global
      cascade of overload failures when highly loaded nodes or edges are removed due to
      attacks or failures. Since a small attack or failure has the potential to trigger
      a global cascade, a fundamental question regards the possible strategies of
      defense to prevent the cascade from propagating through the entire network. Here
      we introduce and investigate a costless strategy of defense based on a selective
      further removal of nodes and edges, right after the initial attack or failure.
      This intentional removal of network elements is shown to drastically reduce the
      size of the cascade.

PMID- 15447155
TI  - Comment on "Nonclassical paths in the recurrence spectrum of diamagnetic atoms".

PMID- 15447154
TI  - The hierarchical backbone of complex networks.
AB  - Given any complex directed network, a set of acyclic subgraphs can be extracted
      that will provide valuable information about its hierarchical structure. This
      Letter presents how the interpretation of the network weight matrix as a
      transition matrix allows the hierarchical backbone to be identified and
      characterized in terms of the concepts of hierarchical degree, which expresses
      the total weights of virtual edges established along successive transitions. The
      potential of the proposed approach is illustrated with respect to simulated
      random and preferential-attachment networks as well as real data related to word
      associations and gene sequencing.

PMID- 15447156
TI  - Comment on "Interaction of shear waves and propagating cracks".

PMID- 15447158
TI  - Spectroscopy of superfluid pairing in atomic fermi gases.
AB  - We study the dynamic structure factor for density and spin within the crossover
      from BCS superfluidity of atomic fermions to the Bose-Einstein condensation of
      molecules. Both structure factors are experimentally accessible via Bragg
      spectroscopy and allow for the identification of the pairing mechanism: the spin
      structure factor allows for the determination of the two particle gap, while the
      collective sound mode in the density structure reveals the superfluid state.

PMID- 15447159
TI  - Existence of temperature on the nanoscale.
AB  - We consider a regular chain of quantum particles with nearest neighbor
      interactions in a canonical state with temperature T. We analyze the conditions
      under which the state factors into a product of canonical density matrices with
      respect to groups of n particles each and under which these groups have the same
      temperature T. In quantum mechanics the minimum group size n(min) depends on the
      temperature T, contrary to the classical case. We apply our analysis to a
      harmonic chain and find that n(min)=const for temperatures above the Debye
      temperature and n(min) proportional to T(-3) below.

PMID- 15447160
TI  - Three-dimensional solitary waves and vortices in a discrete nonlinear Schrodinger
      lattice.
AB  - In a benchmark dynamical-lattice model in three dimensions, the discrete
      nonlinear Schrodinger equation, we find discrete vortex solitons with various
      values of the topological charge S. Stability regions for the vortices with
      S=0,1,3 are investigated. The S=2 vortex is unstable and may spontaneously
      rearranging into a stable one with S=3. In a two-component extension of the
      model, we find a novel class of stable structures, consisting of vortices in the
      different components, perpendicularly oriented to each other. Self-localized
      states of the proposed types can be observed experimentally in Bose-Einstein
      condensates trapped in optical lattices and in photonic crystals built of
      microresonators.

PMID- 15447161
TI  - Single-atom density of states of an optical lattice.
AB  - We consider a single atom in an optical lattice, subject to a harmonic trapping
      potential. The problem is treated in the tight-binding approximation, with an
      extra parameter kappa denoting the strength of the harmonic trap. It is shown
      that the kappa-->0 limit of this problem is singular, in the sense that the
      density of states for a very shallow trap (kappa-->0) is qualitatively different
      from that of a translationally invariant lattice (kappa=0). The physics of this
      difference is discussed, and densities of states and wave functions are exhibited
      and explained.

PMID- 15447162
TI  - Kinematic approach to the mixed state geometric phase in nonunitary evolution.
AB  - A kinematic approach to the geometric phase for mixed quantal states in
      nonunitary evolution is proposed. This phase is manifestly gauge invariant and
      can be experimentally tested in interferometry. It leads to well-known results
      when the evolution is unitary.

PMID- 15447163
TI  - Experimental observation of the tilting mode of an array of vortices in a dilute
      Bose-Einstein condensate.
AB  - We have measured the precession frequency of a vortex lattice in a Bose-Einstein
      condensate of Rb87 atoms. The observed mode corresponds to a collective motion in
      which all the vortices in the array are tilted by a small angle with respect to
      the z axis (the symmetry axis of the trapping potential) and synchronously rotate
      about this axis. This motion corresponds to excitation of a Kelvin wave along the
      core of each vortex and we have verified that it has the handedness expected for
      such helical waves, i.e., precession in the opposite sense to the rotational flow
      around the vortices.

PMID- 15447164
TI  - Relating quantum privacy and quantum coherence: an operational approach.
AB  - Given many realizations of a state or a channel as a resource, two parties can
      generate a secret key as well as entanglement. We describe protocols to perform
      the secret key distillation (as it turns out, with optimal rate). Then we show
      how to achieve optimal entanglement generation rates by "coherent" implementation
      of a class of secret key agreement protocols, proving the long-conjectured
      "hashing inequality."

PMID- 15447165
TI  - Quantum process tomography of a controlled-NOT gate.
AB  - We demonstrate complete characterization of a two-qubit entangling process--a
      linear optics controlled-NOT gate operating with coincident detection--by quantum
      process tomography. We use a maximum-likelihood estimation to convert the
      experimental data into a physical process matrix. The process matrix allows an
      accurate prediction of the operation of the gate for arbitrary input states and a
      calculation of gate performance measures such as the average gate fidelity,
      average purity, and entangling capability of our gate, which are 0.90, 0.83, and
      0.73, respectively.

PMID- 15447166
TI  - Fermionic field theory for trees and forests.
AB  - We prove a generalization of Kirchhoff's matrix-tree theorem in which a large
      class of combinatorial objects are represented by non-Gaussian Grassmann
      integrals. As a special case, we show that unrooted spanning forests, which arise
      as a q-->0 limit of the Potts model, can be represented by a Grassmann theory
      involving a Gaussian term and a particular bilocal four-fermion term. We show
      that this latter model can be mapped, to all orders in perturbation theory, onto
      the N-vector model at N=-1 or, equivalently, onto the sigma model taking values
      in the unit supersphere in R(1|2). It follows that, in two dimensions, this
      fermionic model is perturbatively asymptotically free.

PMID- 15447167
TI  - Gluing initial data sets for general relativity.
AB  - We establish an optimal gluing construction for general relativistic initial data
      sets. The construction is optimal in two distinct ways. First, it applies to
      generic initial data sets and the required (generically satisfied) hypotheses are
      geometrically and physically natural. Second, the construction is completely
      local in the sense that the initial data is left unaltered on the complement of
      arbitrarily small neighborhoods of the points about which the gluing takes place.
      Using this construction we establish the existence of cosmological, maximal
      globally hyperbolic, vacuum space-times with no constant mean curvature spacelike
      Cauchy surfaces.

PMID- 15447168
TI  - Explosive hydrogen burning of 17O in classical novae.
AB  - We report on the observation of a new resonance at E(lab)(R)=190 keV in the
      17O(p,gamma)18F reaction. The measured resonance strength amounts to
      omegagamma(pgamma)=(1.2+/-0.2)x10(-6) eV. With this new value, the uncertainties
      in the 17O(p,gamma)18F and 17O(p,alpha)14N thermonuclear reaction rates are
      reduced by orders of magnitude at nova temperatures. Our significantly improved
      reaction rates have major implications for the galactic synthesis of 17O, the
      stellar production of the radioisotope 18F, and the predicted oxygen isotopic
      ratios in nova ejecta.

PMID- 15447169
TI  - Proposed new test of spin effects in general relativity.
AB  - The recent discovery of a double-pulsar PSR J0737-3039A/B provides an opportunity
      of unequivocally observing, for the first time, spin effects in general
      relativity. Existing efforts involve detection of the precession of the spinning
      body itself. However, for a close binary system, spin effects on the orbit may
      also be discernible. Not only do they add to the advance of the periastron (by an
      amount which is small compared to the conventional contribution) but they also
      give rise to a precession of the orbit about the spin direction. The measurement
      of such an effect would also give information on the moment of inertia of
      pulsars.

PMID- 15447170
TI  - Initial conditions of the universe: how much isocurvature is allowed?
AB  - We investigate the constraints imposed by current data on correlated mixtures of
      adiabatic and nonadiabatic primordial perturbations. We discover subtle flat
      directions in parameter space that tolerate large (approximately 60%) fractions
      of nonadiabatic fluctuations. In particular, larger values of the baryon density
      and a spectral tilt are allowed. The cancellations in the degenerate directions
      are explored and the role of priors is elucidated.

PMID- 15447171
TI  - Low reheating temperature and the visible sterile neutrino.
AB  - We present here a scenario, based on a low reheating temperature T(R)<<100 MeV at
      the end of (the last episode of) inflation, in which the coupling of sterile
      neutrinos to active neutrinos can be as large as experimental bounds permit (thus
      making this neutrino "visible" in future experiments). In previous models this
      coupling was forced to be very small to prevent a cosmological overabundance of
      sterile neutrinos. Here the abundance depends on how low the reheating
      temperature is. For example, the sterile neutrino required by the Liquid
      Scintillator Neutrino Detector result may not have any cosmological problem
      within our scenario.

PMID- 15447176
TI  - Final-state interaction as the origin of the Cronin effect.
AB  - The Cronin effect that refers to the enhancement of hadron spectra at
      intermediate p(T) with increasing A in pA collisions is traditionally explained
      in terms of the broadening of the parton transverse momentum in the initial
      state. We show that recent data on the nuclear modification factor at eta=0 for
      d+Au collisions can be understood in terms of the recombination of soft and
      shower partons in the final state. It is the centrality dependence of the soft
      parton density that leads to the Cronin effect.

PMID- 15447175
TI  - Pseudorapidity distribution of charged particles in d+Au collisions at
      sqrt[sNN]=200 GeV.
AB  - The measured pseudorapidity distribution of primary charged particles in minimum
      bias d+Au collisions at sqrt[s(NN)]=200 GeV is presented for the first time. This
      distribution falls off less rapidly in the gold direction as compared to the
      deuteron direction. The average value of the charged particle pseudorapidity
      density at midrapidity is <dN(ch)/d eta>|eta|< or =0.6)=9.4+/-0.7(syst) and the
      integrated primary charged particle multiplicity in the measured region is 82+/
      6(syst). Estimates of the total charged particle production, based on
      extrapolations outside the measured pseudorapidity region, are also presented.
      The pseudorapidity distribution, normalized to the number of participants in d+Au
      collisions, is compared to those of Au+Au and p+(-)p systems at the same energy.
      The d+Au distribution is also compared to the predictions of the parton
      saturation model, as well as microscopic models.

PMID- 15447177
TI  - Identifying neutrinos and antineutrinos in neutral-current scattering reactions.
AB  - We study neutrino-induced nucleon knockout from nuclei. Expressions for the
      induced polarization are derived within the framework of the independent-nucleon
      model and the nonrelativistic plane-wave approximation. Large dissimilarities in
      the nucleon polarization asymmetries are observed between neutrino- and
      antineutrino-induced processes. These asymmetries represent a potential way to
      distinguish between neutrinos and antineutrinos in neutral-current neutrino
      scattering on nuclei. We discuss astrophysical applications of these polarization
      asymmetries. Our findings are illustrated for neutrino scattering on 16O and 208P
      b.

PMID- 15447178
TI  - Unveiling the origin of shape coexistence in lead isotopes.
AB  - Shape coexistence in the nuclei (182-192)Pb is analyzed with the Hartree-Fock
      Bogoliubov approach and the Gogny force. Good agreement with the experimental
      energies is found for the coexisting spherical, oblate, and prolate states.
      Contrary to the established interpretation, it is found that the low-lying
      prolate and oblate 0+ states are predominantly characterized by neutron
      correlations whereas the protons behave, in general, rather as spectators than
      playing an active role.

PMID- 15447179
TI  - First-order superradiant phase transitions in a multiqubit cavity system.
AB  - We predict the existence of novel first-order phase transitions in a general
      class of multiqubit cavity systems. Apart from atomic systems, the associated
      superradiant phase transition should be observable in a variety of solid-state
      experimental systems, including the technologically important case of interacting
      quantum dots coupled to an optical cavity mode.

PMID- 15447174
TI  - Search for the lepton-flavor-violating decay tau- -->micro-eta at Belle.
AB  - We have searched for the lepton flavor violating decay tau(-)-->micro(-)eta using
      a data sample of 84.3 fb(-1) accumulated with the Belle detector at KEK. The eta
      meson was detected through the decay modes: eta-->gammagamma and pi(+)pi(-)pi(0).
      No signal candidates are found, and we obtain an upper limit for the branching
      fraction B(tau(-)-->micro(-)eta)<3.4 x 10(-7) at the 90% confidence level.

PMID- 15447180
TI  - Vibrationally resolved K-shell photoionization of CO with circularly polarized
      light.
AB  - Diffraction of a low energy (<4 eV) carbon-K-photoelectron wave that is created
      inside a CO molecule by absorption of a circularly polarized photon is
      investigated. The measurements resolve the vibrational states of the K-shell
      ionized CO+ molecule and display the photoelectron diffraction patterns in the
      molecular frame. These show significant variation for the different vibrational
      states. This effect is stronger than predicted by state-of-the-art theory. As
      this study is performed close to C-K-threshold and, therefore, far below the
      molecule's sigma-shape resonance, this surprisingly strong effect is not related
      to that resonance phenomenon.

PMID- 15447181
TI  - Ionization and recombination in intense, short electric field pulses.
AB  - We investigate ionization and excitation of H(1s) in the limit of very short
      electric field pulses, analytically and numerically and both in the limit of
      small and extremely large peak electric fields. We identify a process of
      recombination akin to Rabi flopping from the continuum and give an analytic
      expression for this process after a single-cycle strong-field pulse.

PMID- 15447182
TI  - Interpretation of quantum and classical angular momentum polarization moments.
AB  - This Letter presents a derivation of the relationship between the quantum and
      classical descriptions of angular momentum polarization. The results involve an
      "uncertainty broadening" term that directly expresses the restrictions imposed by
      the uncertainty principle. It is argued that neglect of this term can lead to
      error in the interpretation of theoretical or experimental angular momentum
      polarization data. Functions that take the uncertainty broadening into account,
      appropriate for use in quantum or quasiclassical descriptions of spatial
      distributions of angular momenta, are defined.

PMID- 15447183
TI  - Self-synchronization and dissipation-induced threshold in collective atomic
      recoil lasing.
AB  - Networks of globally coupled oscillators exhibit phase transitions from
      incoherent to coherent states. Atoms interacting with the counterpropagating
      modes of a unidirectionally pumped high-finesse ring cavity form such a globally
      coupled network. The coupling mechanism is provided by collective atomic recoil
      lasing, i.e., cooperative Bragg scattering of laser light at an atomic density
      grating, which is self-induced by the laser light. Under the rule of an
      additional friction force, the atomic ensemble is expected to undergo a phase
      transition to a state of synchronized atomic motion. We present the experimental
      investigation of this phase transition by studying the threshold behavior of this
      lasing process.

PMID- 15447184
TI  - Muonic molecules in superintense laser fields.
AB  - We study theoretically the ionization and dissociation of muonic molecular ions
      (e.g., dd mu) in superintense laser fields. We predict that the bond breaks by
      tunneling of the lightest ion through a bond-softened barrier at intensity I > or
      =10(21) W/cm(2). Ionization of the muonic atomic fragment occurs at much higher
      intensity I > or =6 x 10(22) W/cm(2). Since the field controls the ion trajectory
      after dissociation, it forces recollision of a approximately 10(5)-10(6) eV ion
      with the muonic atom. Recollision can trigger a nuclear reaction with sub-laser
      cycle precision. In general, molecules can serve as precursors for laser control
      of nuclear processes.

PMID- 15447185
TI  - Hall effect of light.
AB  - We derive the semiclassical equation of motion for the wave packet of light
      taking into account the Berry curvature in momentum-space. This equation
      naturally describes the interplay between orbital and spin angular momenta, i.e.,
      the conservation of the total angular momentum of light. This leads to the shift
      of wave-packet motion perpendicular to the gradient of the dielectric constant,
      i.e., the polarization-dependent Hall effect of light. An enhancement of this
      effect in photonic crystals is also proposed.

PMID- 15447172
TI  - Bound on the ratio of decay amplitudes for -B0-->J/psiK*0 and B0-->J/psiK*0.
AB  - We have measured the time-dependent decay rate for the process B-->J/psiK(*0)
      (892) in a sample of about 88x10(6) Upsilon(4S)-->B(-)B decays collected with the
      BABAR detector at the PEP-II asymmetric-energy B factory at SLAC. In this sample
      we study flavor-tagged events in which one neutral B meson is reconstructed in
      the J/psiK(*0) or J/psi(-)K(*0) final state. We measure the coefficients of the
      cosine and sine terms in the time-dependent asymmetries for J/psiK(*0) and J/psi(
      )K(*0), find them to be consistent with the standard model expectations, and set
      upper limits at 90% confidence level (C.L.) on the decay amplitude ratios |A((
      )B(0)-->J/psiK(*0))|/|A(B0-->J/psiK(*0))|<0.26 and |A(B0-->J/psi(-)K(*0))|/|A((
      )B(0)-->J/psi(-)K(*0))|<0.32. For a single ratio of wrong-flavor to favored
      amplitudes for B0 and (-)B(0) combined, we obtain an upper limit of 0.25 at 90%
      C.L.

PMID- 15447186
TI  - Optimal dispersion relations for enhanced electromagnetic power deposition in
      dissipative slabs.
AB  - Broadband analysis of a prototype model associated with electromagnetic waves
      absorption in a lossy dielectric slab renders a closed-form theoretical
      prediction of an infinite number of optimal absorption paths in the complex
      refractive index domain. While for thin slabs (in terms of incident wavelength
      range) each path corresponds to a lossy Fabry-Perot-type resonance modes of order
      m=0,1,2,... and provides at least 50% absorption of the incident wave power even
      for ultrathin slabs, for optimal thick slabs, the fraction of absorbed power,
      asymptotically estimated via Lambert W function, increases up to 100% for
      consecutive continuation of the m=1 normal mode only.

PMID- 15447187
TI  - Observation of two-photon above-threshold ionization of rare gases by xuv
      harmonic photons.
AB  - We have successfully observed two-photon above-threshold ionization in rare gas
      atoms (Ar, Xe, and He) by the fifth harmonic (25 eV photon energy) of a KrF
      laser. Use of the energy-resolved photoelectron counting system together with our
      laser, providing strong 25 eV radiation at 40-100 Hz, enabled us to detect the
      very weak single-color two-photon above-threshold ionization signals.
      Experimental data are in good agreement with our theoretical calculations newly
      developed along the line of multichannel quantum defect theory.

PMID- 15447188
TI  - Kerr-nonlinearity optical parametric oscillation in an ultrahigh-Q toroid
      microcavity.
AB  - Kerr-nonlinearity induced optical parametric oscillation in a microcavity is
      reported for the first time. Geometrical control of toroid microcavities enables
      a transition from stimulated Raman to optical parametric-oscillation regimes.
      Optical parametric oscillation is observed at record low threshold levels (174
      micro-Watts of launched power) more than 2 orders of magnitude lower than for
      optical-fiber-based optical parametric oscillation. In addition to their
      microscopic size (typically tens of microns), these oscillators are wafer based,
      exhibit high conversion efficiency (36%), and are operating in a highly ideal
      "two photon" emission regime, with near-unity (0.97+/-0.03) idler-to-signal
      ratio.

PMID- 15447189
TI  - Controlled generation and steering of spatial gap solitons.
AB  - We demonstrate the first fully controlled generation of immobile and slow spatial
      gap solitons in nonlinear periodic systems with band-gap spectra, and observe the
      key features of gap solitons that distinguish them from discrete solitons,
      including a dynamical transformation of gap solitons due to nonlinear interband
      coupling. We also describe theoretically and confirm experimentally the effect of
      the anomalous steering of gap solitons in optically induced photonic lattices.

PMID- 15447190
TI  - Generalized synchronization of spatiotemporal chaos in a liquid crystal spatial
      light modulator.
AB  - We demonstrate generalized synchronization in a spatiotemporal chaotic system, a
      liquid crystal spatial light modulator with optoelectronic feedback.

PMID- 15447191
TI  - Mechanism of desynchronization in the finite-dimensional Kuramoto model.
AB  - We study how a decrease of the coupling strength causes a desynchronization in
      the Kuramoto model of N globally coupled phase oscillators. We show that, if the
      natural frequencies are distributed uniformly or close to that, the synchronized
      state can robustly split into any number of phase clusters with different average
      frequencies, even culminating in complete desynchronization. In the simplest case
      of N=3 phase oscillators, the course of the splitting is controlled by a Cherry
      flow. The general N-dimensional desynchronization mechanism is numerically
      illustrated for N=5.

PMID- 15447173
TI  - Measurement of the B-->Xsl+l- branching fraction with a sum over exclusive modes.
AB  - We measure the branching fraction for the flavor-changing neutral-current process
      B-->X(s)l(+)l(-) with a sample of 89x10(6) Upsilon(4S)-->BBmacr; events recorded
      with the BABAR detector at the PEP-II e(+)e(-) storage ring. The final state is
      reconstructed from e(+)e(-) or micro(+)micro(-) pairs and a hadronic system X(s)
      consisting of one K+/- or K(0)(S) and up to two pions, with at most one pi(0). We
      observe a signal of 40+/-10(stat)+/-2(syst) events and extract the inclusive
      branching fraction B(B-->X(s)l(+)l(-))=(5.6+/-1.5(stat)+/-0.6(exp syst)+/
      1.1(model syst))x10(-6) for ml(+)(l(-))>0.2 GeV/c(2).

PMID- 15447192
TI  - Capture into resonance: a method for efficient control.
AB  - To achieve large changes in adiabatic invariants using small control input, a
      conservative dynamical system must possess an internal resonance. Capture into
      resonance is an inherently probabilistic process. We propose a control method to
      make it more structured. We study the motion of charged particles in an
      electromagnetic field as an example of such a system. When the nominal dynamics
      brings particles close to a resonance surface, a short control pulse forces the
      capture of a particle into the resonance with the wave. A captured particle is
      transported by the wave across the energy levels. The second pulse releases a
      particle from the resonance when the desired energy level is achieved. We discuss
      the distribution of energy achieved by the method.

PMID- 15447193
TI  - Strouhal-Reynolds number relationship for vortex streets.
AB  - A rationale for the empirically observed Strouhal-Reynolds number relation for
      vortex shedding in the wake of a cylinder is provided. This rationale derives
      from a mechanism of vortex formation observed in numerical simulations of two
      dimensional vortex shedding coupled with an order of magnitude estimate of the
      terms in the vorticity transport equation based on this mechanism.

PMID- 15447194
TI  - Self-assembly and vortices formed by microparticles in weak electrolytes.
AB  - We carried out experimental studies of the self-assembly of metallic micron-size
      particles in poorly conducting liquid subject to a constant electric field.
      Depending on the experimental conditions, the particles self-assemble into long
      chains directed along the electric field lines and form vortices and other
      structures. The vortices perform Brownian-type random motion due to self-induced
      chaotic hydrodynamic flows. We measured the diffusivity constant of the vortices
      and the conductivity and mechanical stiffness of the chains.

PMID- 15447195
TI  - Experimental determination of dust-particle charge in a discharge plasma at
      elevated pressures.
AB  - The charge of dust particles is determined experimentally in a bulk dc discharge
      plasma in the pressure range 20-100 Pa. The charge is obtained by two independent
      methods: one based on an analysis of the particle motion in a stable particle
      flow and another on an analysis of the transition of the flow to an unstable
      regime. Molecular-dynamics simulations of the particle charging for conditions
      similar to those of the experiment are also performed. The results of both
      experimental methods and the simulations demonstrate good agreement. The charge
      obtained is several times smaller than predicted by the collisionless orbital
      motion theory, and thus the results serve as an experimental indication that ion
      neutral collisions significantly affect particle charging.

PMID- 15447196
TI  - Alpha-channeling simulation experiment in the DIII-D tokamak.
AB  - Alfven instabilities can reduce the central magnetic shear via redistribution of
      energetic ions. They can sustain a steady state internal transport barrier as
      demonstrated in this DIII-D tokamak experiment. Improvement in burning plasma
      performance based on this mechanism is discussed.

PMID- 15447197
TI  - Mode transition induced by low-frequency current in dual-frequency capacitive
      discharges.
AB  - The mode transition induced by varying the low-frequency current in low-pressure
      dual-frequency discharges in argon is found through particle-in-cell or Monte
      Carlo simulations. As the low-frequency (2 MHz) current increases for the fixed
      high-frequency (27 MHz) current, the electron distribution function (EDF) changes
      from Druyvesteyn to bi-Maxwellian (in alpha mode) or Maxwellian-type (in gamma
      mode), along with the significant drop in the effective electron temperature. It
      is shown that this EDF evolution is attributed to the transition from collisional
      to collisionless property (but not stochastic heating) of the low-energy
      electrons as well as the alpha-gamma transition.

PMID- 15447198
TI  - Dislocation nucleation in shocked fcc solids: effects of temperature and
      preexisting voids.
AB  - Quantitative behaviors of shock-induced dislocation nucleation are investigated
      by means of molecular dynamics simulations on fcc Lennard-Jones solids: a model
      argon. In perfect crystals, it is found that the Hugoniot elastic limit (HEL) is
      a linearly decreasing function of temperature: from near-zero to melting
      temperatures. In a defective crystal with a void, dislocations are found to
      nucleate on the void surface. Also, HEL drastically decreases to 15% of the
      perfect crystal when the void radius is 3.4 nanometers. The decrease of HEL
      becomes larger as the void radius increases, but HEL becomes insensitive to
      temperature.

PMID- 15447199
TI  - Mechanisms for liquid slip at solid surfaces.
AB  - One of the oldest unresolved problems in fluid mechanics is the nature of liquid
      flow along solid surfaces. It is traditionally assumed that across the liquid
      solid interface, liquid and solid speeds exactly match. However, recent
      observations document that on the molecular scale, liquids can slip relative to
      solids. We formulate a model in which the liquid dynamics are described by a
      stochastic differential-difference equation, related to the Frenkel-Kontorova
      equation. The model, in agreement with molecular dynamics simulations, reveals
      that slip occurs via two mechanisms: localized defect propagation and concurrent
      slip of large domains. Well-defined transitions occur between the two mechanisms.

PMID- 15447200
TI  - Growth of unidirectional molecular rows of cysteine on Au(110)-(1 x 2) driven by
      adsorbate-induced surface rearrangements.
AB  - Using scanning tunneling microscopy we have studied the nucleation and growth of
      unidirectional molecular rows upon adsorption of the amino acid cysteine onto the
      anisotropic Au(110)-(1 x 2) surface under ultrahigh vacuum conditions. By
      modeling a large variety of possible molecular adsorption geometries using
      density-functional theory calculations, we find that in the optimum, lowest
      energy configuration, no significant intermolecular interactions exist along the
      growth direction. Instead the driving force for formation of the unidirectional
      molecular rows is an adsorbate-induced surface rearrangement, providing favorable
      adsorption sites for the molecules.

PMID- 15447201
TI  - Reaction of the oxygen molecule at the Si(100)-SiO2 interface during silicon
      oxidation.
AB  - Using constrained ab initio molecular dynamics, we investigate the reaction of
      the O2 molecule at the Si(100)-SiO2 interface during Si oxidation. The reaction
      proceeds sequentially through the incorporation of the O2 molecule in a Si-Si
      bond and the dissociation of the resulting network O2 species. The oxidation
      reaction occurs nearly spontaneously and is exothermic, irrespective of the O2
      spin state or of the amount of excess negative charge available at the interface.
      The reaction evolves through the generation of network coordination defects
      associated with charge transfers. Our investigation suggests that the Si
      oxidation process is fully governed by diffusion.

PMID- 15447202
TI  - Novel local free energy minimum on the Cu(001) surface.
AB  - High-resolution LEED (low-energy electron diffraction) data of Cu(001) reveal an
      uniaxial in-plane lattice reconstruction by 1%. One-dimensional nanogrooves
      induced by ion bombardment involve the creation of steps that enable this
      reconstruction. This is the first verification of van der Merwe's prediction of
      step facilitated reconstruction. We confirm the predicted dependence on step
      orientation: <100> steps allow stress-relief and <110> steps do not, consistent
      with the known elastic anisotropy. Similar behavior is predicted for other
      nonreconstructed (001) surfaces of 3d and 4d metals.

PMID- 15447203
TI  - Nonlocality and short-range wetting phenomena.
AB  - We propose a nonlocal interfacial model for 3D short-range wetting at planar and
      nonplanar walls. The model is characterized by a binding-potential functional
      depending only on the bulk Ornstein-Zernike correlation function, which arises
      from different classes of tubelike fluctuations that connect the interface and
      the substrate. The theory provides a physical explanation for the origin of the
      effective position-dependent stiffness and binding potential in approximate local
      theories and also obeys the necessary classical wedge covariance relationship
      between wetting and wedge filling. Renormalization group and computer simulation
      studies reveal the strong nonperturbative influence of nonlocality at critical
      wetting, throwing light on long-standing theoretical problems regarding the order
      of the phase transition.

PMID- 15447204
TI  - Molecular chemisorption as the theoretically preferred pathway for water
      adsorption on ideal rutile TiO2(110).
AB  - By taking careful account of slab thickness and adsorbate orientation effects we
      present, for the first time, periodic density functional calculations predicting
      the preference of water to adsorb in a molecular state on the ideal rutile
      TiO2(110) surface at all coverages < or =1 monolayer (ML). Moreover, while this
      has been predicted previously for 1/4 ML coverage [Phys. Rev. Lett. 87, 266104
      (2001)]], we show that the assertion made in that work, that dissociation is
      energetically unfeasible on the ideal surface, is incorrect. Our results thus
      resolve a long-standing discrepancy between theory and experiment and
      significantly improve the understanding of water chemistry on TiO2 surfaces.

PMID- 15447205
TI  - Kosterlitz-Thouless transition for 4He films adsorbed to rough surfaces.
AB  - We report the study of adsorption isotherms of 4He on several well characterized
      rough CaF2 surfaces using a quartz crystal microbalance technique at 1.672 K. The
      signature of decoupled mass observed on crossing the Kosterlitz-Thouless
      transition as a function of 4He film thickness decreases and becomes increasingly
      difficult to identify as the surface roughness is increased. A peak in the
      dissipation, indicative of the onset of superfluidity, changes little with
      roughness.

PMID- 15447206
TI  - Determination of the local concentrations of Mn interstitials and antisite
      defects in GaMnAs.
AB  - We present a method for the determination of the local concentrations of
      interstitial and substitutional Mn atoms and As antisite defects in GaMnAs. The
      method relies on the sensitivity of the structure factors of weak reflections to
      the concentrations and locations of these minority constituents. High spatial
      resolution is obtained by combining structure factor measurement and x-ray
      analysis in a transmission electron microscope. We demonstrate the prevalence of
      interstitials with As nearest neighbors in as-grown layers.

PMID- 15447207
TI  - Nonlocal Coulomb interactions and metal-insulator transition in Ti2O3: a cluster
      LDA+DMFT approach.
AB  - We present an ab initio quantum theory of the metal-insulator transition in
      Ti2O3. The recently developed cluster LDA+DMFT scheme is applied to describe the
      many-body features of this compound. The conventional single site DMFT cannot
      reproduce a low temperature insulating phase for any reasonable values of the
      Coulomb interaction. We show that the nonlocal Coulomb interactions and the
      strong chemical bonding within the Ti-Ti pair is the origin of the small gap
      insulating ground state of Ti2O3.

PMID- 15447208
TI  - Entanglement and quantum phase transition in the extended Hubbard model.
AB  - We study quantum entanglement in a one-dimensional correlated fermionic system.
      Our results show, for the first time, that entanglement can be used to identify
      quantum phase transitions in fermionic systems.

PMID- 15447209
TI  - Electronic structure of bases in DNA duplexes characterized by resonant
      photoemission spectroscopy near the Fermi level.
AB  - The electronic structure of bases in DNA duplexes was investigated by resonant
      photoemission spectroscopy near the Fermi level, in order to specify charge
      migration mechanisms. We observed a kinetic energy shift of N-KLL Auger electrons
      and an intensity enhancement of valence electrons on the resonant photoemission
      spectra for both poly(dG).poly(dC) and poly(dA).poly(dT) DNAs. These directly
      show the localized unoccupied states of the bases. We conclude that the charge
      hopping model is pertinent for electric conduction in a DNA duplex, when
      electrons pass through the unoccupied states.

PMID- 15447210
TI  - Direct generation of a voltage and current by gas flow over carbon nanotubes and
      semiconductors.
AB  - We report here a direct generation of measurable voltages and currents when a gas
      flows over a variety of solids even at the modest speed of a few meters per
      second. The underlying mechanism is an interesting interplay of Bernoulli's
      principle and the Seebeck effect: Pressure differences along streamlines give
      rise to temperature differences across the sample; these in turn produce the
      measured voltage. The electrical signal is quadratically dependent on the Mach
      number M and proportional to the Seebeck coefficient of the solids. Results are
      presented for doped Si and Ge, single wall and multiwall carbon nanotubes, and
      graphite. Our results show that gas flow sensors and energy conversion devices
      can be constructed based on direct generation of electrical signals.

PMID- 15447211
TI  - Intrinsic charge transport on the surface of organic semiconductors.
AB  - The air-gap field-effect technique enabled realization of the intrinsic (not
      limited by static disorder) polaronic transport on the surface of rubrene
      (C42H28) crystals over a wide temperature range. The signatures of this intrinsic
      transport are the anisotropy of the carrier mobility, mu, and the growth of mu
      with cooling. Anisotropy of mu vanishes in the activation regime at low
      temperatures, where the transport is dominated by shallow traps. The deep traps,
      introduced by x-ray radiation, increase the field-effect threshold without
      affecting mu, an indication that the filled traps do not scatter polarons.

PMID- 15447212
TI  - Localization and nonlinear resistance in telescopically extended nanotubes.
AB  - We have measured the electrical resistance R between the ends of a multiwall
      carbon nanotube during telescopic extension of the nanotube. R increases
      monotonically with extension and is hysteresis free, demonstrating that a
      telescoping nanotube constitutes a near-ideal nanometer-scale rheostat. The
      functional form of R is nonlinear and consistent with an exponential form
      predicted for a one-dimensional localized system, with a characteristic
      localization length 1000-1500 nm.

PMID- 15447213
TI  - Amorphouslike density of gap states in single-crystal pentacene.
AB  - We show that optical and electrical measurements on pentacene single crystals can
      be used to extract the density of states in the highest occupied molecular
      orbital-lowest unoccupied molecular orbital band gap. It is found that these
      highly purified crystals possess band tails broader than those typically observed
      in inorganic amorphous solids. Results on field-effect transistors fabricated
      from similar crystals imply that the gap state density is much larger within 5-10
      nm of the gate dielectric. Thus, organic thin-film transistors for such
      applications as flexible displays might be significantly improved by reducing
      these defects.

PMID- 15447214
TI  - Spin uncoupling in free Nb clusters: support for nascent superconductivity.
AB  - Molecular beam Stern-Gerlach deflection measurements on Nb clusters (Nb(N),
      N<100) show that at very low temperatures the odd-N clusters deflect due to a
      single unpaired spin that is uncoupled from the cluster. At higher temperatures
      the spin is coupled and no deflections are observed. Spin uncoupling occurs
      concurrently with the transition to the recently found ferroelectric state, which
      has superconductor characteristics [Science 300, 1265 (2003)]]. Spin uncoupling
      (also seen in V, Ta, and Al clusters) is analogous to the reduction of spin
      relaxation rates observed in bulk superconductors below T(c).

PMID- 15447215
TI  - Ratchetlike dynamics of fluxons in annular Josephson junctions driven by
      biharmonic microwave fields.
AB  - Experimental observation of the unidirectional motion of a topological soliton
      driven by a biharmonic ac force of zero mean is reported. The observation is made
      by measuring the current-voltage characteristics for a fluxon trapped in an
      annular Josephson junction that was placed into a microwave field. The dependence
      of the fluxon mean velocity at zero dc bias versus the phase shift between the
      first and second harmonic of the driving force is in qualitative agreement with
      theoretical expectations.

PMID- 15447216
TI  - Electronic transport in underdoped YBa2Cu3O7-delta nanowires: evidence for
      fluctuating domain structures.
AB  - We have measured the transport properties of a series of underdoped
      YBa(2)Cu(3)O(7-delta) nanowires fabricated with widths of 100-250 nm. We observe
      large telegraphlike fluctuations in the resistance between the pseudogap
      temperature T* and the superconducting transition temperature T(c), consistent
      with the formation and dynamics of a domain structure. We also find anomalous
      hysteretic steps in the current-voltage characteristics well below T(c).

PMID- 15447217
TI  - Probing decoherence with electromagnetically induced transparency in
      superconductive quantum circuits.
AB  - Superconductive quantum circuits comprise quantized energy levels that may be
      coupled via microwave electromagnetic fields. Described in this way, one may draw
      a close analogy to atoms with internal (electronic) levels coupled by laser light
      fields. In this Letter, we present a superconductive analog to
      electromagnetically induced transparency that utilizes superconductive quantum
      circuit designs of present day experimental consideration. We discuss how a
      superconductive analog to electromagnetically induced transparency can be used to
      establish macroscopic coherence in such systems and, thereby, be utilized as a
      sensitive probe of decoherence.

PMID- 15447218
TI  - Enhancement of Josephson phase diffusion by microwaves.
AB  - We report an experimental and theoretical study of the phase diffusion in small
      Josephson junctions under microwave irradiation. A peculiar enhancement of the
      phase diffusion by microwaves is observed. The enhancement manifests itself by a
      pronounced current peak in the current-voltage characteristics. The voltage
      position V(top) of the peak increases with the power P of microwave radiation as
      V(top) proportional to sqrt[P], while its current amplitude weakly decreases with
      P. As the microwave frequency increases, the peak feature evolves into Shapiro
      steps with a finite slope. Our theoretical analysis, taking into account the
      enhancement of incoherent superconducting current by multiphoton absorption, is
      in good agreement with experimental data.

PMID- 15447219
TI  - Spin and charge pumping by ferromagnetic-superconductor order parameters.
AB  - We study transport in ferromagnetic-superconductor/normal-metal systems. It is
      shown that charge and spin currents are pumped from ferromagnetic superconductors
      into adjacent normal metals by adiabatic changes in the order parameters induced
      by external electromagnetic fields. Spin and charge pumping identify the symmetry
      of the superconducting order parameter, e.g., singlet pairing or triplet pairing
      with opposite or equal spin pairing. Consequences for ferromagnetic-resonance
      experiments are discussed.

PMID- 15447220
TI  - Spinons in the strongly correlated copper oxide chains in SrCuO2.
AB  - We have investigated the spin dynamics in the strongly correlated chain copper
      oxide SrCuO2 for energies up to greater, similar 0.6 eV using inelastic neutron
      scattering. We observe a gapless continuum of magnetic excitations, which is well
      described by the "Muller ansatz" for the two-spinon continuum in the S=1/2
      antiferromagnetic Heisenberg spin chain. The lower boundary of the continuum
      extends up to approximately 360 meV, which corresponds to an exchange constant
      J=226(12) meV.

PMID- 15447221
TI  - Magnetic-field-induced condensation of triplons in Han Purple pigment BaCuSi2O6.
AB  - Besides being an ancient pigment, BaCuSi2O6 is a quasi-2D magnetic insulator with
      a gapped spin dimer ground state. The application of strong magnetic fields
      closes this gap, creating a gas of bosonic spin triplet excitations. The topology
      of the spin lattice makes BaCuSi2O6 an ideal candidate for studying the Bose
      Einstein condensation of triplet excitations as a function of the external
      magnetic field, which acts as a chemical potential. In agreement with quantum
      Monte Carlo numerical simulations, we observe a distinct lambda anomaly in the
      specific heat together with a maximum in the magnetic susceptibility upon cooling
      down to liquid helium temperatures.

PMID- 15447222
TI  - Permanent magnetism, magnetic anisotropy, and hysteresis of thiol-capped gold
      nanoparticles.
AB  - We report on the experimental observation of magnetic hysteresis up to room
      temperature in thiol-capped Au nanoparticles with 1.4 nm size. The coercive field
      ranges from 860 Oe at 5 K to 250 Oe at 300 K. It is estimated that the Au atoms
      exhibit a magnetic moment of mu=0.036mu(B). However, Au nanoparticles with
      similar size but stabilized by means of a surfactant, i.e., weak interaction
      between protective molecules and Au surface atoms, are diamagnetic, as bulk Au
      samples are. The apparent ferromagnetism is consequently associated with 5d
      localized holes generated through Au-S bonds. These holes give rise to localized
      magnetic moments that are frozen in due to the combination of the high spin-orbit
      coupling (1.5 eV) of gold and the symmetry reduction associated with two types of
      bonding: Au-Au and Au-S.

PMID- 15447223
TI  - One-dimensional character of combination modes in the resonance Raman scattering
      of carbon nanotubes.
AB  - Resonance Raman spectroscopy with an energy tunable system is used to analyze the
      600-1100 cm(-1) spectral region in single-wall carbon nanotubes. Sharp peaks are
      associated with the combination of zone folded optic and acoustic branches from
      2D graphite. These combination modes exhibit a peculiar dependence on the
      excitation laser energy that is explained on the basis of a highly selective
      resonance process that considers phonons and electrons in low dimensional
      materials.

PMID- 15447224
TI  - Induced transparency by intersubband plasmon coupling in a quantum well.
AB  - We study coupling of two intersubband plasmons associated with dipole-allowed
      cascading transitions in a quantum well. We show that the coupling can lead to
      the disappearance of the lower-energy resonance accompanied by an anticrossing
      behavior. Such coupling induced anomalies are of collective and resonant nature
      and provide the first example of Coulomb interaction induced transparency. Our
      numerical results from a microscopic theory are confirmed by an analytical model.

PMID- 15447225
TI  - Picosecond view of microscopic-scale polarization clusters in paraelectric
      BaTiO3.
AB  - The polarization clusters existing in both the ferroelectric and the paraelectric
      phase of BaTiO3 are directly observed and characterized for the first time by a
      picosecond soft x-ray laser speckle technique. These dynamic clusters appear
      continuously across the Curie temperature T(c). The clusters' distance increases
      approximately linearly with temperature, while their mean size does not change
      significantly. The polarization exhibits a maximum at a temperature about 5
      degrees C above T(c). The clusters' short-range correlation strength diverges as
      (T-T(c))(-0.41+/-0.02) as temperature decreases toward T(c).

PMID- 15447226
TI  - Correlations among hydrogen bonds in liquid water.
AB  - By performing computer simulations of water with the TIP5P potential we show that
      structures formed by two or more hydrogen bonds affect the dynamical and static
      properties of water, especially in the vicinity of freezing temperature. In
      particular, the short time correlation between two coupled hydrogen bonds cannot
      be predicted assuming the statistical independence of the single hydrogen bonds.
      This introduces an additional relaxation time of approximately 9 ps close to the
      freezing point. We also find that the time persistence of structures formed by
      several hydrogen bonds (the first solvation shell) correlates with the local
      density, which is smaller around water molecules with a long-living environment.

PMID- 15447227
TI  - Shear-induced network-to-network transition in a block copolymer melt.
AB  - A tricontinuous (10,3)c network phase is documented in a poly(cyclohexylethylene
      b-ethylethylene-b-ethylene) triblock copolymer melt based on small-angle x-ray
      scattering. Application of shear transforms the self-assembled soft material into
      a single crystal (10,3)d network while preserving the short-range threefold
      connector geometry. Long-range topological restructuring reduces the space group
      symmetry, from Fddd to Pnna, maintaining orthorhombic lattice symmetry. Both
      phases are stable to long time annealing, indicative of nearly degenerate free
      energies and prohibitive kinetic barriers.

PMID- 15447228
TI  - Transient and oscillatory granular shear flow.
AB  - The forces and particle motion during transient and oscillatory shear of granular
      material are investigated experimentally. In a shear cell of Taylor-Couette-type
      we find that how a granular shear flow starts depends strongly on the prior shear
      direction. If the shear direction is reversed, the material goes through a
      transient period during which the material compacts, the shear force is small,
      and the shear band is wide. Three-dimensional confocal imaging of particle
      rearrangements during shear reversal shows that bulk and surface flows are
      comparable. Repeated reversals, or oscillations of the shear direction, lead to
      additional compaction, which can be described by a stretched exponential, similar
      to compaction induced by tapping.

PMID- 15447229
TI  - Connectivities and synchronous firing in cortical neuronal networks.
AB  - Network connectivities ((-)k) of cortical neural cultures are studied by
      synchronized firing and determined from measured correlations between
      fluorescence intensities of firing neurons. The bursting frequency (f) during
      synchronized firing of the networks is found to be an increasing function of (
      )k. With f taken to be proportional to (-)k, a simple random model with a (-)k
      dependent connection probability p((-)k).has been constructed to explain our
      experimental findings successfully.

PMID- 15447230
TI  - Chaotic boundaries of nematic polymers in mixed shear and extensional flows.
AB  - Chaotic orientational dynamics of sheared nematic polymers is documented in
      laboratory experiments and predicted by Doi-Hess kinetic theory for infinitely
      thin rods. We address robustness of rheochaos when simple shear is modified by a
      planar straining flow, and the macromolecules have finite aspect ratio. We
      predict persistence of sheared chaotic response up to a threshold straining flow
      strength and minimum aspect ratio, beyond which chaotic behavior is arrested.
      More intriguing, a straining component can induce chaos from periodic shear
      responses.

PMID- 15447231
TI  - Force field parametrization through fitting on inflection points in isotherms.
AB  - We present a method to determine potential parameters in molecular simulations of
      confined systems through fitting on experimental isotherms with inflection
      points. The procedure uniquely determines the adsorbent-adsorbate interaction
      parameters and is very sensitive to the size parameter. The inflection points in
      the isotherms are often related to a subtle interplay between different
      adsorption sites. If a force field can predict this interplay, it also reproduces
      the remaining part of the isotherm correctly, i.e., the Henry coefficients and
      saturation loadings.

PMID- 15447232
TI  - Floating liquid phase in sedimenting colloid-polymer mixtures.
AB  - Density functional theory and computer simulation are used to investigate
      sedimentation equilibria of colloid-polymer mixtures within the Asakura-Oosawa
      Vrij model of hard sphere colloids and ideal polymers. When the ratio of buoyant
      masses of the two species is comparable to the ratio of differences in density of
      the coexisting bulk (colloid) gas and liquid phases, a stable "floating liquid"
      phase is found, i.e., a thin layer of liquid sandwiched between upper and lower
      gas phases. The full phase diagram of the mixture under gravity shows coexistence
      of this floating liquid phase with a single gas phase or a phase involving liquid
      gas equilibrium; the phase coexistence lines meet at a triple point. This
      scenario remains valid for general asymmetric binary mixtures undergoing bulk
      phase separation.

PMID- 15447233
TI  - Photon trajectories in incoherent atomic radiation trapping as Levy flights.
AB  - Photon trajectories in incoherent radiation trapping for Doppler, Lorentz, and
      Voigt line shapes under complete frequency redistribution are shown to be Levy
      flights. The jump length (r) distributions display characteristic long tails. For
      the Lorentz line shape, the asymptotic form is a strict power law r(-3/2), while
      for Doppler the asymptotic is r(-2)(ln(r)(-1/2). For the Voigt profile, the
      asymptotic form always has a Lorentz character, but the trajectory is a self
      affine fractal with two characteristic Hausdorff scaling exponents.

PMID- 15447234
TI  - Insulating behavior of a trapped ideal Fermi gas.
AB  - We investigate theoretically and experimentally the center-of-mass motion of an
      ideal Fermi gas in a combined periodic and harmonic potential. We find a
      crossover from a conducting to an insulating regime as the Fermi energy moves
      from the first Bloch band into the band gap of the lattice. The conducting regime
      is characterized by an oscillation of the cloud about the potential minimum,
      while in the insulating case the center of mass remains on one side of the
      potential.

PMID- 15447235
TI  - Weak measurements with arbitrary probe states.
AB  - The exact conditions on valid probe states for weak measurements are derived. It
      is demonstrated that weak measurements can be performed with any probe state with
      vanishing probability current density. This condition is found both for weak
      measurements of noncommuting observables and for c-number observables. In
      addition, the interaction between object and probe must be sufficiently weak.
      Strange weak values can be observed also with mixed probe states, but not for c
      number observables.

PMID- 15447236
TI  - Time-dependent perturbation theory with a classical limit.
AB  - We construct a quantum mechanical perturbation theory which uses the multiple
      time scale technique. Working with the time translation operator, we use a
      variant on the method of Bender and Bettencourt. Our perturbation theory smoothly
      crosses over to the classical result as Planck's -->0. It is seen that this
      technique has a nonperturbative element built into it.

PMID- 15447237
TI  - Luttinger liquid of polarons in one-dimensional boson-fermion mixtures.
AB  - We use the bosonization approach to investigate quantum phases of boson-fermion
      mixtures (BFM) of atoms confined to one dimension by an anisotropic optical
      lattice. For a BFM with a single species of fermions we find a charge-density
      wave phase, a fermion pairing phase, and a phase separation regime. We also
      obtain the rich phase diagram of a BFM with two species of fermions. We
      demonstrate that these phase diagrams can be understood in terms of polarons,
      i.e., atoms "dressed" by screening clouds of the other atom species. Techniques
      to detect the resulting quantum phases are discussed.

PMID- 15447238
TI  - Magnetization plateaus for spin-one bosons in optical lattices: Stern-Gerlach
      experiments with strongly correlated atoms.
AB  - We consider insulating states of spin-one bosons in optical lattices in the
      presence of a weak magnetic field. For the states with more than one atom per
      lattice site we find a series of quantum phase transitions between states with
      fixed magnetization and a canted nematic phase. In the presence of a global
      confining potential, this unusual phase diagram leads to several novel phenomena,
      including the formation of magnetization plateaus. We discuss how these effects
      can be observed using spatially resolved spin polarization measurements.

PMID- 15447239
TI  - Bose-Einstein condensation of particle-hole pairs in ultracold fermionic atoms
      trapped within optical lattices.
AB  - We investigate the Bose-Einstein condensation (BEC, superfluidity) of particle
      hole pairs in ultracold fermionic atoms with repulsive interactions and arbitrary
      polarization, which are trapped within optical lattices. In the strongly
      repulsive limit, the dynamics of particle-hole pairs can be described by a hard
      core Bose-Hubbard model. The insulator-superfluid and charge-density-wave- (CDW)
      superfluid phase transitions can be induced by decreasing and increasing the
      potential depths with controlling the trapping laser intensity, respectively. The
      parameter and polarization dependence of the critical temperatures for the
      ordered states (BEC and/or CDW) are discussed simultaneously.

PMID- 15447240
TI  - Radio frequency selective addressing of localized atoms in a periodic potential.
AB  - We study the localization and addressability of ultracold atoms in a combined
      parabolic and periodic potential. Such a potential supports the existence of
      localized stationary states and we show that applying a radio frequency field
      allows us to selectively address atoms in these states. This method is used to
      measure the energy and momentum distribution of the atoms in the localized
      states. We also discuss possible extensions of this scheme to address and
      manipulate atoms in single lattice sites.

PMID- 15447241
TI  - Entanglement within the quantum trajectory description of open quantum systems.
AB  - The degree of entanglement in an open quantum system varies according to how
      information in the environment is read. A measure of this contextual entanglement
      is introduced based on quantum trajectory unravelings of the open system
      dynamics. It is used to characterize the entanglement in a driven quantum system
      of dimension 2 x infinity where the entanglement is induced by the environmental
      interaction. A detailed mechanism for the environment-induced entanglement is
      given.

PMID- 15447242
TI  - Conversion efficiency of ultracold fermionic atoms to bosonic molecules via
      Feshbach resonance sweep experiments.
AB  - We explain why the experimental efficiency observed in the conversion of
      ultracold Fermi gases of 40K and 6Li atoms into diatomic Bose gases is limited to
      0.5 when the Feshbach resonance sweep rate is sufficiently slow to pass
      adiabatically through the Landau-Zener transition but faster than "the collision
      rate" in the gas, and increases beyond 0.5 when it is slower. The 0.5 efficiency
      limit is due to the preparation of a statistical mixture of two spin states,
      required to enable s-wave scattering. By constructing the many-body state of the
      system we show that this preparation yields a mixture of even and odd parity pair
      states, where only even parity can produce molecules. The odd parity spin
      symmetric states must decorrelate before the constituent atoms can further
      Feshbach scatter, thereby increasing the conversion efficiency; "the collision
      rate" is the pair decorrelation rate.

PMID- 15447243
TI  - Unconditional security of coherent-state quantum key distribution with a strong
      phase-reference pulse.
AB  - We prove the unconditional security of a quantum key distribution protocol in
      which bit values are encoded in the phase of a weak coherent-state pulse relative
      to a strong reference pulse. In contrast with implementations in which a weak
      pulse is used as a substitute for a single-photon source, the achievable key rate
      is found to decrease only linearly with the transmission of the channel.

PMID- 15447244
TI  - Teleportation on a quantum dot array.
AB  - We present a model of quantum teleportation protocol based on a double quantum
      dot array. The unknown qubit is encoded using a pair of quantum dots, with one
      excess electron, coupled by tunneling. It is shown how to create a maximally
      entangled state using an adiabatically increasing Coulomb repulsion between
      different dot pairs. This entangled state is exploited to perform teleportation
      again using an adiabatic coupling between itself and the incoming unknown state.
      Finally, a sudden separation of Bob's qubit allows a time evolution of Alice's,
      which amounts to a modified version of standard Bell measurement. A transmission
      over a long distance could be obtained by considering the entangled state of a
      chain of N coupled double quantum dots. The system is shown to be increasingly
      robust with N against decoherence due to phonons.

PMID- 15447246
TI  - Phase diagram of the square-lattice three-state Potts antiferromagnet with a
      staggered polarization field.
AB  - We study a square-lattice three-state Potts antiferromagnet with a staggered
      polarization field at finite temperature. Numerically treating the transfer
      matrices, we determine two phase boundaries separating the model-parameter space
      into three parts. We confirm that one of them belongs to the ferromagnetic three
      state Potts criticality, which is in accord with a recent prediction, and another
      to the Ising-type; these are both corresponding to the massless renormalization
      group flows stemming from the Gaussian fixed points. We also discuss a field
      theory to describe the latter Ising transition.

PMID- 15447245
TI  - Chirality in quantum computation with spin cluster qubits.
AB  - We study corrections to the Heisenberg interaction between several lateral,
      single-electron quantum dots. We show, using exact diagonalization, that three
      body chiral terms couple triangular configurations to external sources of flux
      rather strongly. The chiral corrections impact single-qubit encodings utilizing
      loops of three or more Heisenberg coupled quantum dots.

PMID- 15447247
TI  - Entropy production of Brownian macromolecules with inertia.
AB  - We investigate the nonequilibrium steady-state thermodynamics of single Brownian
      macromolecules with inertia under feedback control in an isothermal ambient
      fluid. With the control being represented by a velocity-dependent external force,
      we find such an open system can have a negative entropy production rate, and we
      develop a mesoscopic theory consistent with the second law. We propose an
      equilibrium condition and define a class of external force, which includes the
      transverse Lorentz force, leading to equilibrium.

PMID- 15447248
TI  - Superdiffusion on a comb structure.
AB  - We study specific properties of particles transport by exploring an exact
      solvable model, a so-called comb structure, where diffusive transport of
      particles leads to subdiffusion. A performance of the Levy-like process enriches
      this transport phenomenon. It is shown that an inhomogeneous convection flow is a
      mechanism for the realization of the Levy-like process. It leads to
      superdiffusion of particles on the comb structure. This superdiffusion is an
      enhanced one with an arbitrary large transport exponent, but all moments are
      finite. A frontier case of superdiffusion, where the transport exponent
      approaches infinity, is studied. The log-normal distribution with the
      exponentially fast superdiffusion is obtained for this case.

PMID- 15447249
TI  - Dark matter and dark energy from the solution of the strong CP problem.
AB  - The Peccei-Quinn (PQ) solution of the strong CP problem requires the existence of
      axions, which are viable candidates for dark matter. If the Nambu-Goldstone
      potential of the PQ model is replaced by a potential V(|Phi|) admitting a tracker
      solution, the scalar field |Phi| can account for dark energy, while the phase of
      Phi yields axion dark matter. If V is a supergravity (SUGRA) potential, the model
      essentially depends on a single parameter, the energy scale Lambda. Once we set
      Lambda approximately equal to 10(10) GeV at the quark-hadron transition, |Phi|
      naturally passes through values suitable to solve the strong CP problem, later
      growing to values providing fair amounts of dark matter and dark energy.

PMID- 15447250
TI  - Neutrinoless universe.
AB  - We consider the consequences for the relic neutrino abundance if extra neutrino
      interactions are allowed, e.g., the coupling of neutrinos to a light (compared to
      m(nu)) boson. For a wide range of couplings not excluded by other considerations,
      the relic neutrinos would annihilate to bosons at late times and thus make a
      negligible contribution to the matter density today. This mechanism evades the
      neutrino mass limits arising from large scale structure.

PMID- 15447251
TI  - Determination of the a0-a2 pion scattering length from K+-->pi+pi0pi0 decay.
AB  - We present a new method for the determination of the pi-pi scattering length
      combination a(0)-a(2), based on the study of the pi(0)pi(0) spectrum in K+-
      >pi(0)pi(0)pi(+) in the vicinity of the pi(+)pi(-) threshold. The method requires
      a minimum of theoretical input, and is potentially very accurate.

PMID- 15447253
TI  - Universality of the rho meson coupling in effective field theory.
AB  - It is shown that both the universal coupling of the rho meson and the
      Kawarabayashi-Suzuki-Riadzuddin-Fayyazuddin expression for the magnitude of its
      coupling constant follow from the requirement that chiral perturbation theory of
      pions, nucleons, and rho mesons is a consistent effective field theory. The
      prerequisite of the derivation is that all ultraviolet divergences can be
      absorbed in the redefinition of fields and the available parameters of the most
      general effective Lagrangian.

PMID- 15447254
TI  - Partonic calculation of the two-photon exchange contribution to elastic electron
      proton scattering at large momentum transfer.
AB  - We estimate the two-photon exchange contribution to elastic electron-proton
      scattering at large momentum transfer through the scattering off a parton in the
      proton. We relate the two-photon exchange amplitude to the generalized parton
      distributions which appear in hard exclusive processes. We find that when taking
      the polarization transfer determinations of the form factors as input, adding in
      the 2-photon correction does reproduce the Rosenbluth cross sections.

PMID- 15447252
TI  - Measurement of the generalized polarizabilities of the proton in virtual Compton
      scattering at Q2=0.92 and 1.76 GeV2.
AB  - We report a virtual Compton scattering study of the proton at low c.m. energies.
      We have determined the structure functions P(LL)-P(TT)/epsilon and P(LT), and the
      electric and magnetic generalized polarizabilities (GPs) alpha(E)(Q2) and
      beta(M)(Q2) at momentum transfer Q(2)=0.92 and 1.76 GeV2. The electric GP shows a
      strong falloff with Q2, and its global behavior does not follow a simple dipole
      form. The magnetic GP shows a rise and then a falloff; this can be interpreted as
      the dominance of a long-distance diamagnetic pion cloud at low Q2, compensated at
      higher Q2 by a paramagnetic contribution from piN intermediate states.

PMID- 15447255
TI  - In-medium isovector piN amplitude from low-energy pion scattering.
AB  - Differential cross sections for elastic scattering of 21.5 MeV positive and
      negative pions by Si, Ca, Ni, and Zr have been measured as part of a study of the
      pion-nucleus potential across the threshold. The "anomalous" repulsion in the s
      wave term was observed, as is the case with pionic atoms. The extra repulsion can
      be accounted for by a chiral-motivated model where the pion decay constant is
      modified in the medium. Unlike in pionic atoms, the anomaly cannot be removed by
      merely introducing an empirical on-shell energy dependence.

PMID- 15447256
TI  - Fine structure in the energy region of the isoscalar giant quadrupole resonance:
      characteristic scales from a wavelet analysis.
AB  - Fine structure in the energy region of the isoscalar giant quadrupole resonance
      in nuclei is observed in high-resolution proton scattering experiments at iThemba
      LABS over a wide mass range. A novel method based on wavelet transforms is
      introduced for the extraction of scales characterizing the fine structure. A
      comparison with microscopic model calculations including two-particle two-hole
      (2p2h) degrees of freedom identifies the coupling to surface vibrations as the
      main source of the observed scales. A generic pattern is also found for the
      stochastic coupling to the background of the more complex states.

PMID- 15447257
TI  - Quasidynamical symmetry in an interacting boson model phase transition.
AB  - The apparent persistence of symmetry in the face of strong symmetry-breaking
      interactions is examined in a many-boson model. The model exhibits a transition
      between two phases associated with U(5) and O(6) symmetries, respectively, as the
      value of a control parameter progresses from 0 to 1. The remarkable fact is that,
      in spite of strong mixing of the symmetries for intermediate values of the
      control parameter, the model continues to exhibit the characteristics of its
      closest symmetry limit for all but a relatively narrow transition region that
      becomes progressively narrower as the boson number increases. This phenomenon is
      explained in terms of quasidynamical symmetry.

PMID- 15447258
TI  - Tuning the scattering length with an optically induced Feshbach resonance.
AB  - We demonstrate optical tuning of the scattering length in a Bose-Einstein
      condensate as predicted by Fedichev et al. [Phys. Rev. Lett. 77, 2913 (1996)]. In
      our experiment, atoms in a 87Rb condensate are exposed to laser light which is
      tuned close to the transition frequency to an excited molecular state. By
      controlling the power and detuning of the laser beam we can change the atomic
      scattering length over a wide range. In view of laser-driven atomic losses, we
      use Bragg spectroscopy as a fast method to measure the scattering length of the
      atoms.

PMID- 15447259
TI  - Suppression of Bragg scattering by collective interference of spatially ordered
      atoms with a high-Q cavity mode.
AB  - When N driven atoms emit in phase into a high-Q cavity mode, the intracavity
      field generated by collective scattering interferes destructively with the pump
      driving the atoms. Hence atomic fluorescence is suppressed and cavity loss
      becomes the dominant decay channel for the whole ensemble. Microscopically, 3D
      light-intensity minima are formed in the vicinity of the atoms that prevent
      atomic excitation and form a regular lattice. The effect gets more pronounced for
      large atom numbers, when the sum of the atomic decay rates exceeds the rate of
      cavity losses and one would expect the opposite behavior. These results provide
      new insight into recent experiments on collective atomic dynamics in cavities.

PMID- 15447260
TI  - Limits on universality in ultracold three-boson recombination.
AB  - The recombination rate for three identical bosons has been calculated to test the
      limits of its universal behavior. It has been obtained for several different
      collision energies and scattering lengths a up to 10(5) a.u., giving rates that
      vary over 15 orders of magnitude. We find that universal behavior is limited to
      the threshold region characterized by E equal or less than Planck's
      2/2mu(12)a(2), where E is the total energy and mu(12) is the two-body reduced
      mass. The analytically predicted infinite series of resonance peaks and
      interference minima is truncated to no more than three of each for typical
      experimental parameters.

PMID- 15447261
TI  - Photoassociation spectroscopy of laser-cooled ytterbium atoms.
AB  - We report the photoassociation spectroscopy of laser-cooled ytterbium atoms in an
      optical trap. We observed more than 90 photoassociation resonances of vibrational
      levels in the (1)Sigma(+)(u) state, including 80 consecutive series, up to 490
      GHz detuning with respect to the atomic resonance. From the resonance frequencies
      we derived the atomic radiative lifetime of the (6s6p) 1P1 state to be 5.464+/
      0.005 ns, which is about 2 orders of magnitude improvement over previous results.
      We also observed line broadening of resonances, which is ascribed to the
      predissociation to the triplet states, and estimated the transition probability
      to be 0.2. Furthermore, we observed the decrease of the photoassociation signal
      intensity, from which the scattering length is estimated to be equal to or less
      than 3 nm.

PMID- 15447262
TI  - Breakup of H2 in singly ionizing collisions with fast protons: channel-selective
      low-energy electron spectra.
AB  - Dissociative as well as nondissociative single ionization of H2 by 6 MeV proton
      impact has been studied in a kinematically complete experiment by measuring the
      momentum vectors of the electron and the H+ fragment or the H+2 target ion,
      respectively. For the two ionization pathways, the electron spectra reveal the
      role of autoionization of the doubly and singly excited states of H2. The latter
      explicitly involve the coupling between the electronic and the nuclear motion of
      the molecule. This is a clear manifestation of a breakdown of the Born
      Oppenheimer approximation.

PMID- 15447263
TI  - Dynamic correlation in wave propagation in random media.
AB  - Field spectra are analyzed to yield the time-resolved statistics of pulsed
      transmission through quasi-one-dimensional dielectric media with static disorder.
      The normalized intensity correlation function with displacement and polarization
      rotation for an incident pulse of linewidth sigma at delay time t is a function
      only of the field correlation function, which is identical to that found for
      steady-state excitation, and of kappa(sigma)(t), the residual degree of intensity
      correlation at points at which the field correlation function vanishes. The
      dynamic probability distribution of normalized intensity depends only upon
      kappa(sigma)(t). Steady-state statistics are recovered in the limit sigma-->0, in
      which kappa(sigma=0) is the steady-state degree of correlation.

PMID- 15447264
TI  - Enhanced nonlinear optical response of one-dimensional metal-dielectric photonic
      crystals.
AB  - We describe a new type of artificial nonlinear optical material composed of a one
      dimensional metal-dielectric photonic crystal. Because of the resonant nature of
      multiple Bragg reflections, the transmission within the transmission band can be
      quite large, even though the transmission through the same total thickness of
      bulk metal would be very small. This procedure allows light to penetrate into the
      highly nonlinear metallic layers, leading to a large nonlinear optical response.
      We present experimental results for a Cu/SiO(2) crystal which displays a strongly
      enhanced nonlinear optical response (up to 12X) in transmission.

PMID- 15447265
TI  - Ultrahigh efficiency laser wavelength conversion in a gas-filled hollow core
      photonic crystal fiber by pure stimulated rotational Raman scattering in
      molecular hydrogen.
AB  - We report on the generation of pure rotational stimulated Raman scattering in a
      hydrogen gas hollow-core photonic crystal fiber. Using the special properties of
      this low-loss fiber, the normally dominant vibrational stimulated Raman
      scattering is suppressed, permitting pure conversion to the rotational Stokes
      frequency in a single-pass configuration pumped by a microchip laser. We report
      92% quantum conversion efficiency (40 nJ pulses in 2.9 m fiber) and threshold
      energies (3 nJ in 35 m) more than 1 x 10(6) times lower than previously reported.
      The control of the output spectral components by varying only the pump
      polarization is also shown. The results point to a new generation of highly
      engineerable and compact laser sources.

PMID- 15447266
TI  - Weak dynamical localization in periodically kicked cold atomic gases.
AB  - Quantum kicked rotor was recently realized in experiments with cold atomic gases
      and standing optical waves. As predicted, it exhibits dynamical localization in
      the momentum space. Here we consider the weak-localization regime concentrating
      on the Ehrenfest time scale. The latter accounts for the spread time of a minimal
      wave packet and is proportional to the logarithm of the Planck constant. We show
      that the onset of the dynamical localization is essentially delayed by four
      Ehrenfest times, and give quantitative predictions suitable for an experimental
      verification.

PMID- 15447267
TI  - Extraction of plumes in turbulent thermal convection.
AB  - We present a scheme to extract the velocity of buoyant structures in turbulent
      thermal convection from simultaneous local velocity and temperature measurements.
      Applying this scheme to measurements taken at positions within the convection
      cell where the buoyant structures are dominated by plumes, we obtain the
      temperature dependence of the plume velocity and understand our results using the
      equations of motion. We further obtain the scaling behavior of the average local
      heat flux in the vertical direction at the cell center with the Rayleigh number
      and find that the scaling exponent is different from that measured for the
      Nusselt number. This difference leads to the conclusion that heat cannot be
      mainly transported through the central region of the convection cell.

PMID- 15447268
TI  - Secondary instabilities of hexagonal patterns in a Benard-Marangoni convection
      experiment.
AB  - We have identified experimentally secondary instability mechanisms that restrict
      the stable band of wave numbers for ideal hexagons in Benard-Marangoni
      convection. We use "thermal laser writing" to impose long wave perturbations of
      ideal hexagonal patterns as initial conditions and measure the growth rates of
      the perturbations. For epsilon=0.46 our results suggest a longitudinal phase
      instability limits stable hexagons at a high wave number while a transverse phase
      instability limits low wave number hexagons.

PMID- 15447269
TI  - Thermodynamic potential in local turbulence simulations.
AB  - For the reduced local equations customary in, e.g., the computation of turbulence
      in tokamaks the energy is still a conserved quantity. However, kinetic and
      magnetic energy do not appear in the reduced energy functional and thus are not
      constrained by it, since they are ordered small compared to the fluctuations of
      internal energy in the reduction process. Constraints on velocity and field
      fluctuations can be derived using instead the generalized grand canonical
      potential, which is conserved in reversible processes. This is exemplified for
      the Boltzmann, gyrokinetic, and fluid equations.

PMID- 15447270
TI  - Kinetic susceptibility and transport theory of collisional plasmas.
AB  - A system of nonlocal electron transport equations for electrostatic perturbations
      in (omega,k) space in a high-Z plasma is derived from the Fokker-Planck equation
      for arbitrary relations between the time, space, and collisionality scales. The
      closed scheme for obtaining the longitudinal plasma susceptibility
      epsilon(omega,k) in the entire (omega,k) plane is proposed. Regions in the
      (omega,k) plane have been mapped for problems such as the relaxation of the local
      temperature enhancement with a time-dependent heat conductivity. The electron
      dielectric permittivity has been calculated over the entire range of parameters,
      including the transition region between Vlasov and Fokker-Planck equation
      solutions.

PMID- 15447271
TI  - Formation and structure of transport barriers during confinement transitions in
      toroidal plasma.
AB  - Density pedestal formation is studied experimentally during spontaneous low-to
      high confinement transitions in the H-1 heliac. Poloidally extended potential
      structures, or zonal flows, seem to play the major role both in the spatial
      structure and in the temporal evolution of the pedestal formation. Zonal flows
      transiently generate radially localized maxima in the radial electric-field shear
      in L mode which coincides with the radial location of the pedestal in H mode.

PMID- 15447272
TI  - Theory and observations of slow-mode solitons in space plasmas.
AB  - A generalized model for one-dimensional magnetosonic structures of large
      amplitude in space plasmas is presented. The model is verified with multipoint
      measurements on Cluster satellites in the magnetosheath and the boundary layer
      under conditions of plasma beta (plasma/magnetic pressure) between 0.1-10. We
      demonstrate good agreement between the model and observations of large amplitude
      structures and wave trains, which represent increases of magnetic field and
      plasma density 2-5 times the ambient values, or local decreases (holes) by
      approximately (50-80)%. Theoretically derived polarization and propagation
      properties of slow-mode nonlinear structures are also in agreement with in situ
      measurements in space.

PMID- 15447273
TI  - Vortex formation and annihilation in three textures of rotating superfluid 3He-A.
AB  - Textures, textural transformation, and formation and annihilation of a single
      vortex were investigated in narrow cylinders with 100 microm radius in A-phase
      under rotation up to 6.28 rad/sec. Three textures were found, depending on the
      cooling conditions of the sample through the superfluid transition temperature
      T(c). We found the gyromagnetic effect of textures; that is, two textures (A or
      B) could be selected either by applying a magnetic field in parallel or anti
      parallel to the rotation axis. The critical angular speed of a single vortex
      formation Omega(f) and that of annihilation Omega(a) for each texture were
      measured. The textural transformation in type A texture was induced by rotation.
      Both type A and B textures held macroscopic angular momentum along the rotation
      axis. We identified the texture for type A, B, and C as Mermin-Ho, radial
      disgyration, and a soliton type of defect along the axis, respectively.

PMID- 15447274
TI  - Prediction of new phases of nitrogen at high pressure from first-principles
      simulations.
AB  - A rich variety of competing phases is predicted for nitrogen at accessible
      pressures, including a new metallic chainlike phase very close in energy to the
      previously predicted cubic gauche phase, and other phases at slightly higher
      energies, e.g., one with N2 and N6 units. Large energy barriers between
      structures can account for recent observations of metastability, and we identify
      a low barrier transition path from the known epsilon phase to the chainlike
      metallic phase. In analogy to MgB2, the metal is anisotropic with multiple Fermi
      surfaces formed from pi and sigma states.

PMID- 15447275
TI  - Avalanches and scaling in plastic deformation.
AB  - Plastic deformation of crystalline materials is a complex nonhomogeneous process
      characterized by avalanches in the motion of dislocations. We study the evolution
      of dislocation loops using an analytically solvable phase-field model of
      dislocations for ductile single crystals during monotonic loading. The
      distribution of dislocation loop sizes is given by P(A) approximately A-sigma,
      with sigma=1.8+/-0.1. The exponent is in agreement with those found in acoustic
      emission experiments. This model also predicts a range of macroscopic behaviors
      in agreement with observation, including hardening with monotonic loading, and a
      maximum in the acoustic emission signal at the onset of yielding.

PMID- 15447276
TI  - Structure and dynamics of hydrogen molecules in the novel clathrate hydrate by
      high pressure neutron diffraction.
AB  - The D2 clathrate hydrate crystal structure was determined as a function of
      temperature and pressure by neutron diffraction for the first time. The hydrogen
      occupancy in the (32+X)H2.136H(2)O, x=0-16 clathrate can be reversibly varied by
      changing the large (hexakaidecahedral) cage occupancy between two and four
      molecules, while remaining single occupancy of the small (dodecahedral) cage.
      Above 130-160 K, the guest D2 molecules were found in the delocalized state,
      rotating around the centers of the cages. Decrease of temperature results in
      rotation freezing followed by a complete localization below 50 K.

PMID- 15447277
TI  - Theoretical strength and the onset of plasticity in bulk metallic glasses
      investigated by nanoindentation with a spherical indenter.
AB  - The mechanical behavior of bulk metallic glasses (BMGs) was investigated by
      nanoindentation with a spherical indenter. The transition from perfectly elastic
      behavior to plastic deformation was clearly observed as a pop-in event (sudden
      displacement excursion) on the load-displacement curves. Hertzian stress analysis
      was used to describe fully the load-displacement behavior during elastic
      deformation and to determine the theoretical shear strengths of the BMGs.

PMID- 15447278
TI  - Universal statistics of the critical depinning force of elastic systems in random
      media.
AB  - We study the rescaled probability distribution of the critical depinning force of
      an elastic system in a random medium. We put in evidence the underlying
      connection between the critical properties of the depinning transition and the
      extreme value statistics of correlated variables. The distribution is Gaussian
      for all periodic systems, while in the case of random manifolds there exists a
      family of universal functions ranging from the Gaussian to the Gumbel
      distribution. Both of these scenarios are a priori experimentally accessible in
      finite, macroscopic, disordered elastic systems.

PMID- 15447279
TI  - Radiotracer diffusion and ionic conduction in a PEO-NaI polymer electrolyte.
AB  - We studied ion transport in amorphous PEO30NaI consisting of poly(ethylene oxide)
      and sodium iodide in a Na-to-O ratio of 30. Diffusion coefficients of the
      radiotracers 22Na and 125I were measured for temperatures between 67 and 180
      degrees C and compared with the overall charge diffusivity deduced from dc
      conductivity data. To explain the observed discrepancy between the sum of the
      tracer diffusivities and the charge diffusivity we propose a detailed model which
      is based on the formation of neutral ion pairs. Evaluating simultaneously all
      experimental data within this model yields not only the true diffusion
      coefficient of all individual species but also the ion-pairing reaction constant
      as a function of temperature.

PMID- 15447280
TI  - Observation of an anomalous density minimum in vitreous silica.
AB  - Vitreous silica is known to have several anomalous variations in its physical
      properties including a temperature dependent density maximum. We report the
      results of high-resolution density relaxation experiments that conclusively show
      for the first time the existence of a density minimum for silica below its glass
      transition temperature at approximately 950 degrees C. This unusual density
      temperature relationship is shown to be consistent with the existence of a
      polyamorphic phase transition in silica with a negative Clapeyron slope.

PMID- 15447281
TI  - Structural analysis of the SiO2/Si100 interface by means of photoelectron
      diffraction.
AB  - The local environment of Si atoms at the interface between a thermally grown SiO2
      film and Si(100) was studied by angle-scanned photoelectron diffraction.
      Experimental photoelectron diffraction patterns for each Si oxidation state were
      obtained from the results of least squares fitting on Si 2p core-level spectra. A
      comparison of the diffraction patterns with multiple-scattering calculations
      including an R-factor analysis was performed. An excellent agreement between
      experimental and simulated data was achieved within the proposed bridge-bonded
      interface model [Phys. Rev. Lett. 84, 4393 (2000)]].

PMID- 15447282
TI  - Contrasting growth modes of Mn on Ge(100) and Ge(111) surfaces: subsurface
      segregation versus intermixing.
AB  - Based on first-principles total energy calculations within density functional
      theory, we show that a low dose of Mn on Ge(100) initiates in a novel subsurface
      growth mode, characterized by easy access to, and strong preference for,
      interstitial sites located between the two topmost Ge layers. Strikingly, such a
      "subsurfactant action" is preserved even during epitaxial growth of additional Ge
      layers, analogous to the well-known phenomenon of surfactant action. In contrast,
      along the [111] orientation, Mn can easily diffuse into the bulk via interstitial
      sites. These results are discussed within the context of dopant control in dilute
      magnetic semiconductors.

PMID- 15447283
TI  - Indication of unusual pentagonal structures in atomic-size Cu nanowires.
AB  - We present a study of the structural and quantum conductance properties of atomic
      size copper nanowires generated by mechanical stretching. The atomistic evolution
      was derived from time-resolved electron microscopy observations and molecular
      dynamics simulations. We have analyzed the quantum transport behavior by means of
      conductance measurements and theoretical calculations. The results suggest the
      formation of an unusual and highly stable pentagonal Cu nanowire with a diameter
      of approximately 0.45 nm and approximately 4.5 conductance quanta.

PMID- 15447284
TI  - Two-step reaction on a strained, nanoscale segmented surface.
AB  - By means of scanning tunneling microscopy and density functional theory
      calculations we demonstrate that on the Rh(110)-(10 x 2)-O surface, a
      prototypical multiphase surface of an oxidized transition metal model catalyst,
      water formation upon H2 exposure is a two-step reaction, with each step requiring
      special active sites. The 1st step initiates at (2 x 1)p2mg-O defect islands in
      the (10 x 2) structure and propagates across the surface as a reaction front,
      removing half of the adsorbed oxygen. The oxygen decorated Rh ridges of the (10 x
      2) structure lose their tensile strain upon this reduction step, whereby
      nanoscale patches of clean Rh become exposed and act as special reaction sites in
      the 2nd reaction step, which therefore initiates homogeneously over the entire
      surface.

PMID- 15447285
TI  - Cumulative mechanical moments and microstructure deformation induced by growth
      shape in columnar solidification.
AB  - The dynamical interaction between columnar interface microstructure and self
      stress, resulting in unforeseen mechanical deformation phenomena, is brought to
      light by means of in situ and real-time synchrotron x-ray topography during
      directional solidification of dilute aluminum alloys. Beyond long-known local
      mechanical stresses, global mechanical constraints are found to be active. In
      particular, column rotation results from deformation caused by the mechanical
      moments associated with the very growth shape, namely, the cumulative torque
      acting together with the cumulative bending moment under gravity. A basic model
      allowing for a qualitative explanation of the observed distinctive features of
      the self-stress effects on microstructure dynamics is proposed.

PMID- 15447286
TI  - Formation of atom wires on vicinal silicon.
AB  - The feasibility of creating atomic wires on vicinal silicon surfaces via
      pseudomorphic step-edge decoration has been analyzed for the case of Ga on
      Si(112). Scanning tunneling microscopy and density functional theory calculations
      indicate the formation of Ga zigzag chains intersected by quasiperiodic vacancy
      lines or "misfit dislocations." This structure strikes a balance between the
      system's drive towards chemical passivation and its need for strain relaxation in
      the atom chains. Spatially fluctuating disorder, intrinsic to the reconstruction,
      originates from the two symmetry-degenerate orientations of the zigzag chains on
      vicinal Si.

PMID- 15447287
TI  - Inhomogeneous metallic phase in a disordered Mott insulator in two dimensions.
AB  - We show that, with increasing randomness, the spectral gap in a 2D Mott-Hubbard
      insulator is destroyed first at a disorder V(c1), while antiferromagnetism
      persists up to a higher V(c2). Most unexpectedly, between V(c1) and V(c2) the
      system is metallic and is sandwiched between the Mott insulator below V(c1) and
      the Anderson insulator above V(c2). The metal is formed when the spectral gap
      gets destroyed locally in regions where the disorder potential is high enough to
      overcome the interelectron repulsion. This generates puddles with enhanced charge
      fluctuations that percolate with increasing disorder, resulting in a spatially
      inhomogeneous metallic phase.

PMID- 15447288
TI  - Decay of correlations in Fermi systems at nonzero temperature.
AB  - The locality of correlation functions is considered for Fermi systems at nonzero
      temperature. We show that for all short-range, lattice Hamiltonians, the
      correlation function of any two fermionic operators decays exponentially with a
      correlation length which is of order the inverse temperature for small
      temperature. We discuss applications to numerical simulation of quantum systems
      at nonzero temperature.

PMID- 15447289
TI  - Transition from Mott insulator to superconductor in GaNb4Se8 and GaTa4Se8 under
      high pressure.
AB  - Electronic conduction in GaM4Se8 (M=Nb,Ta) compounds with the fcc GaMo4S8-type
      structure originates from hopping of localized unpaired electrons (S=1 / 2) among
      widely separated tetrahedral M4 metal clusters. We show that under pressure these
      systems transform from Mott insulators to a metallic and superconducting state
      with T(C)=2.9 and 5.8 K at 13 and 11.5 GPa for GaNb4Se8 and GaTa4Se8,
      respectively. The occurrence of superconductivity is shown to be connected with a
      pressure-induced decrease of the MSe6 octahedral distortion and simultaneous
      softening of the phonon associated with M-Se bonds.

PMID- 15447290
TI  - Core-level x-ray photoemission satellites in ruthenates: a new mechanism
      revealing the Mott transition.
AB  - Core-level x-ray photoemission spectra for the Mott-Hubbard systems are
      calculated by the dynamical mean-field theory based on the exact diagonalization
      method. The spectra show a two-peak structure, screened and unscreened peaks. The
      screened peak is absent in a Mott insulator, but develops into the main peak when
      the correlation strength becomes weak and the system turns metallic. The
      calculated spectral behavior is consistent with the experimental Ru 3d core-level
      spectra of various ruthenates. This new mechanism of the core-level photoemission
      satellite can be utilized to reveal the Mott transition phenomenon in various
      strongly correlated electron systems, especially in nanoscale devices and phase
      separated materials.

PMID- 15447291
TI  - Fermi surface reconstruction in the CDW state of CeTe3 observed by photoemission.
AB  - CeTe3 is a layered compound where an incommensurate charge density wave (CDW)
      opens a large gap ( approximately 400 meV) in optimally nested regions of the
      Fermi surface (FS), whereas other sections with poorer nesting remain ungapped.
      Through angle-resolved photoemission, we identify bands backfolded according to
      the CDW periodicity. They define FS pockets formed by the intersection of the
      original FS and its CDW replica. Such pockets illustrate very directly the role
      of nesting in the CDW formation but they could not be detected so far in a CDW
      system. We address the reasons for the weak intensity of the folded bands, by
      comparing different foldings coexisting in CeTe3.

PMID- 15447292
TI  - All-electron self-consistent GW approximation: application to Si, MnO, and NiO.
AB  - We present a new kind of self-consistent GW approximation based on the all
      electron, full-potential linear muffin-tin orbital method. By iterating the
      eigenfunctions of the GW Hamiltonian, self-consistency in both the charge density
      and the quasiparticle spectrum is achieved. We explain why this form of self
      consistency should be preferred to the conventional one. Some results for Si (a
      representative semiconductor) are presented. Finally we consider many details in
      the electronic structure of the antiferromagnetic insulators MnO and NiO.
      Excellent agreement with experiment is shown for many properties, suggesting that
      a Landau quasiparticle (energy band) picture provides a reasonable description of
      electronic structure even in these correlated materials.

PMID- 15447293
TI  - Polarization of nuclear spins from the conductance of quantum wire.
AB  - We devise an approach to measure the polarization of nuclear spins via
      conductance measurements. Specifically, we study the combined effect of external
      magnetic field, nuclear spin polarization, and Rashba spin-orbit interaction on
      the conductance of a quantum wire. Nonequilibrium nuclear spin polarization
      affects the electron energy spectrum making it time dependent. Changes in the
      extremal points of the spectrum result in time dependence of the conductance. The
      conductance oscillation pattern can be used to obtain information about the
      amplitude of the nuclear spin polarization and extract the characteristic time
      scales of the nuclear spin subsystem.

PMID- 15447294
TI  - One-channel conductor in an ohmic environment: mapping to a Tomonaga-Luttinger
      liquid and full counting statistics.
AB  - It is shown that a one-channel coherent conductor in an Ohmic environment can be
      mapped to the impurity problem in a Tomonaga-Luttinger liquid. This allows one to
      determine nonperturbatively the effect of the environment on I-V curves, and to
      find an exact relationship between dynamic Coulomb blockade and shot noise. We
      investigate critically how this relationship compares to recent proposals in the
      literature. The full counting statistics is determined at zero temperature.

PMID- 15447295
TI  - Interactions suppress quasiparticle tunneling at Hall bar constrictions.
AB  - Tunneling of fractionally charged quasiparticles across a two-dimensional
      electron system on a fractional quantum Hall plateau is expected to be strongly
      enhanced at low temperatures. This theoretical prediction is at odds with recent
      experimental studies of samples with weakly pinched quantum-point-contact
      constrictions in which the opposite behavior is observed. We argue here that this
      unexpected finding is a consequence of electron-electron interactions near the
      point contact.

PMID- 15447296
TI  - Tunable Fermi-edge resonance in an open quantum dot.
AB  - Resonant tunneling in an open mesoscopic quantum dot is proposed as a vehicle to
      realize a tunable Fermi-edge resonance with variable coupling strength. We solve
      the x-ray edge problem for a generic nonseparable scatterer and apply it to
      describe tunneling in a quantum dot. The tunneling current power law exponent is
      linked to the S matrix of the dot. The control of scattering by varying the dot
      shape and coupling to the leads allows us to explore a wide range of exponents.
      The sensitivity of mesoscopic coherence to the Wigner-Dyson ensemble symmetry is
      replicated in the Fermi-edge singularity.

PMID- 15447297
TI  - Dissipation and tunneling in quantum Hall bilayers.
AB  - We discuss the interplay between transport and intrinsic dissipation in quantum
      Hall bilayers, within the framework of a simple thought experiment. We compute,
      for the first time, quantum corrections to the semiclassical dynamics of this
      system. This allows us to reinterpret tunneling measurements on these systems. We
      find a strong peak in the zero-temperature tunneling current that arises from the
      decay of Josephson-like oscillations into incoherent charge fluctuations. In the
      presence of an in-plane field, resonances in the tunneling current develop an
      asymmetric line shape.

PMID- 15447298
TI  - Mesoscopic one-way channels for quantum state transfer via the quantum Hall
      effect.
AB  - We show that the one-way channel formalism of quantum optics has a physical
      realization in electronic systems. In particular, we show that magnetic edge
      states form unidirectional quantum channels capable of coherently transporting
      electronic quantum information. Using the equivalence between one-way photonic
      channels and magnetic edge states, we adapt a proposal for quantum state transfer
      to mesoscopic systems using edge states as a quantum channel, and show that it is
      feasible with reasonable experimental parameters. We discuss how this protocol
      may be used to transfer information encoded in number, charge, or spin states of
      quantum dots, so it may prove useful for transferring quantum information between
      parts of a solid-state quantum computer.

PMID- 15447299
TI  - Magnetic-field-induced Mott transition in a quasi-two-dimensional organic
      conductor.
AB  - We investigated the effect of magnetic field on the highly correlated metal near
      the Mott transition in the quasi-two-dimensional layered organic conductor, kappa
      (BEDT-TTF)(2)Cu[N(CN)(2)]Cl, by the resistance measurements under control of
      temperature, pressure, and magnetic field. It was demonstrated that the marginal
      metallic phase near the Mott transition is susceptible to the field-induced
      localization transition of the first order, as was predicted theoretically. The
      thermodynamic consideration of the present results gives a conceptual pressure
      field phase diagram of the Mott transition at low temperatures.

PMID- 15447300
TI  - Magnetic excitations in a bond-centered stripe phase: spin waves far from the
      semiclassical limit.
AB  - Using a spin-only model, we compute spin excitation spectra in a bond-centered
      stripe state with long-range magnetic order. We employ a bond operator formalism,
      which naturally captures both dimerization and broken spin symmetry in a unified
      framework. At low energies, the spin excitations resemble spin waves, but at
      higher energies they are very similar to spin-one excitations of isolated spin
      ladders. Our theory does well describe neutron scattering data [Nature (London)
      429, 534 (2004)]] on La2-xBaxCuO4, pointing towards bond order in this material.

PMID- 15447301
TI  - Coherently photoinduced ferromagnetism in diluted magnetic semiconductors.
AB  - Ferromagnetism is predicted in undoped diluted magnetic semiconductors
      illuminated by intense sub-band-gap laser radiation. The mechanism for
      photoinduced ferromagnetism is coherence between conduction and valence bands
      induced by the light which leads to an optical exchange interaction. The
      ferromagnetic critical temperature T(C) depends both on the properties of the
      material and on the frequency and intensity of the laser and could be above 1K.

PMID- 15447302
TI  - Dimerized phase and transitions in a spatially anisotropic square lattice
      antiferromagnet.
AB  - We investigate the spatially anisotropic square lattice quantum antiferromagnet.
      The model describes isotropic spin-1/2 Heisenberg chains (exchange constant J)
      coupled antiferromagnetically in the transverse (J( perpendicular )) and diagonal
      (J(x)), with respect to the chain, directions. Classically, the model admits two
      ordered ground states-with antiferromagnetic and ferromagnetic interchain spin
      correlations-separated by a first-order phase transition at J( perpendicular
      )=2J(x). We show that in the quantum model this transition splits into two,
      revealing an intermediate quantum-disordered columnar dimer phase, both in two
      dimensions and in a simpler two-leg ladder version. We describe quantum-critical
      points separating this spontaneously dimerized phase from classical ones.

PMID- 15447303
TI  - Frustration-induced eta inversion in the S=1/2 bond-alternating spin chain.
AB  - We study the frustration-induced enhancement of the incommensurate correlation
      for a bond-alternating quantum spin chain in a magnetic field, which is
      associated with a quasi-one-dimensional organic compound F5PNN. We investigate
      the temperature dependence of the staggered susceptibilities by using the density
      matrix renormalization group, and then find that the incommensurate correlation
      becomes dominant in a certain range of the magnetic field. We also discuss the
      mechanism of this enhancement on the basis of the mapping to the effective S=1/2
      XXZ chain and a possibility of the field-induced incommensurate long-range order.

PMID- 15447304
TI  - Roles of nonequilibrium conduction electrons on the magnetization dynamics of
      ferromagnets.
AB  - The mutual dependence of spin-dependent conduction and magnetization dynamics of
      ferromagnets provides the key mechanisms in various spin-dependent phenomena. We
      compute the response of the conduction electron spins in a spatial and time
      varying magnetization M(r,t) in the time-dependent semiclassical transport
      theory. We show that the induced nonequilibrium conduction spin density in turn
      generates four spin torques acting on the magnetization-with each torque playing
      a different role in magnetization dynamics. By comparing with recent theoretical
      models, we find that one of these torques which has not been previously
      identified is crucial to consistently interpreting experimental data on domain
      wall motion.

PMID- 15447305
TI  - Direct measurement of the single-metal-cluster optical absorption.
AB  - The absorption of a single isolated metal cluster is directly measured using a
      novel far-field optical technique based on modulation of its position. Single
      gold nanoparticles with average diameters down to 5 nm, dispersed on a
      transparent substrate, are optically detected and their absolute absorption cross
      section determined.

PMID- 15447306
TI  - Estimating the memory time induced by exciton-exciton scattering.
AB  - It is shown that lower bounds for the effective memory time induced by two-pair
      correlations can be estimated by monitoring changes of the shape of excitonic
      four-wave-mixing spectra. Experimentally we demonstrate a memory time of at least
      540 fs for a ZnSe single quantum well. Microscopic calculations reveal that this
      lower bound is not sharp. Interactions retarded by more than 800 fs are shown to
      influence the dynamics, reflecting the presence of a long time tail in the memory
      kernel.

PMID- 15447307
TI  - Isotropic to nematic transition of aerosil-disordered liquid crystals.
AB  - We present a high-resolution study of the isotropic to nematic phase transition
      of a low birefringence liquid-crystal compound incorporating an aerosil gel.
      Calorimetry, light scattering, and microscopy data coherently combine to allow
      for an accurate determination of the temperature dependence of the onset of the
      nematic state. The nematic order develops on cooling through two distinct
      processes while the nematic correlation length mildly decreases. We understand
      the doubling of the phase transition as due to a crossover from a random-dilution
      regime, where the silica gel couples to the scalar part of the nematic order
      parameter, to a low-T random-field regime, where the coupling induces distortions
      in the director field.

PMID- 15447308
TI  - Effect of mono- and multivalent salts on angle-dependent attractions between
      charged rods.
AB  - Using molecular dynamics simulations we examine the effective interactions
      between two like-charged rods as a function of angle and separation. In
      particular, we determine how the competing electrostatic repulsions and
      multivalent-ion-induced attractions depend upon concentrations of simple and
      multivalent salts. We find that with increasing multivalent salt, the stable
      configuration of two rods evolves from isolated rods to aggregated perpendicular
      rods to aggregated parallel rods; at sufficiently high concentration, additional
      multivalent salt reduces the attraction. Monovalent salt enhances the attraction
      near the onset of aggregation and reduces it at a higher concentration of
      multivalent salt.

PMID- 15447309
TI  - Kinetic pinning and biological antifreezes.
AB  - Biological antifreezes protect cold-water organisms from freezing. An example is
      the antifreeze proteins (AFP's) that attach to the surface of ice crystals and
      arrest growth. The mechanism for growth arrest has not been heretofore understood
      in a quantitative way. We present a complete theory based on a kinetic model. We
      use the "stones on a pillow" picture. Our theory of the suppression of the
      freezing point as a function of the concentration of the AFP is quantitatively
      accurate. It gives a correct description of the dependence of the freezing point
      suppression on the geometry of the protein, and might lead to advances in design
      of synthetic AFP's.

PMID- 15447310
TI  - Multiple-time scale accelerated molecular dynamics: addressing the small-barrier
      problem.
AB  - We present a method for accelerated molecular-dynamics simulation in systems with
      rare-event dynamics that span a wide range of time scales. Using a variant of
      hyperdynamics, we detect, on the fly, groups of recurrent states connected by
      small energy barriers and we modify the potential-energy surface locally to
      consolidate them into large, coarse states. In this way, fast motion between
      recurrent states is treated within an equilibrium formalism and dynamics can be
      simulated over the longer time scale of the slow events. We apply the method to
      simulate cluster diffusion and the initial growth of Co on Cu(001),where time
      scales spanning more than 6 orders of magnitude are present, and show that the
      method correctly follows the slow events, so that much larger times can be
      simulated than with accelerated molecular dynamics alone.

PMID- 15447311
TI  - Abrupt transition from viscoelastic solidlike to liquidlike behavior in jammed
      materials.
AB  - Using a new rheometrical technique, which makes it possible to determine both the
      velocity field in steady state and the strain field in the very first instants of
      the flow, we show that, beyond a critical deformation, typical pasty materials (a
      foam and a polymeric gel) turn abruptly from a viscoelastic solidlike behavior to
      a steady liquidlike behavior at a shear rate larger than a critical value.

PMID- 15447312
TI  - Gate-controlled atomic quantum switch.
AB  - An atomic-scale quantum conductance switch is demonstrated that allows us to open
      and close an electrical circuit by the controlled and reproducible
      reconfiguration of silver atoms within an atomic-scale junction. The only movable
      parts of the switch are the contacting atoms. The switch is entirely controlled
      by an external electrochemical voltage applied to an independent third gate
      electrode. Controlled switching was performed between a quantized, electrically
      conducting "on state" exhibiting a conductance of G(0)=2e(2)/h ( approximately
      1/12.9 kOmega) or preselectable multiples of this value and an insulating "off
      state."

PMID- 15447313
TI  - Comment on "Bell's theorem without inequalities and without alignments".

PMID- 15447315
TI  - Comment on "Enhancing acceleration radiation from ground-state atoms via cavity
      quantum electrodynamics".

PMID- 15447317
TI  - Comment on "Opening optical four-wave mixing channels with giant enhancement
      using ultraslow pump waves".

PMID- 15447319
TI  - Comment on "Influence of pair breaking and phase fluctuations on disordered high
      T(c) cuprate superconductors".

PMID- 15447321
TI  - Efficient and robust initialization of a qubit register with fermionic atoms.
AB  - We show that fermionic atoms have crucial advantages over bosonic atoms in terms
      of loading in optical lattices for use as a possible quantum computation device.
      After analyzing the change in the level structure of a nonuniform confining
      potential as a periodic potential is superimposed to it, we show how this
      structure combined with the Pauli principle and fermion degeneracy can be
      exploited to create unit occupancy of the lattice sites with very high
      efficiency.

PMID- 15447322
TI  - Vacuum Cerenkov radiation.
AB  - Within the classical Maxwell-Chern-Simons limit of the standard-model extension,
      the emission of light by uniformly moving charges is studied confirming the
      possibility of a Cerenkov-type effect. In this context, the exact radiation rate
      for charged magnetic point dipoles is determined and found in agreement with a
      phase-space estimate under certain assumptions.

PMID- 15447323
TI  - Bell-Klyshko inequalities to characterize maximally entangled states of n qubits.
AB  - This Letter presents the first rigorous proof of the conjecture raised by Gisin
      and Bechmann-Pasquinucci [Phys. Lett. A 246, 1 (1998)]], that the Greenberger
      Horne-Zeilinger states of n qubits and the states obtained from them by local
      unitary transformations are the unique states that maximally violate the Bell
      Klyshko inequalities. The proof is obtained by using the certain algebraic
      properties that Pauli's matrices satisfy and some subtle mathematical techniques.
      Since all states obtained by local unitary transformations of a maximally
      entangled state are equally valid entangled states, we thus give a
      characterization of maximally entangled states of n qubits in terms of the Bell
      type inequality.

PMID- 15447324
TI  - Phase separation in the two-dimensional bosonic Hubbard model with ring exchange.
AB  - We show that soft-core bosons in two dimensions with a ring exchange term exhibit
      a tendency for phase separation. This observation suggests that the thermodynamic
      stability of normal Bose liquid phases driven by ring exchange should be
      carefully examined.

PMID- 15447325
TI  - Renormalization flow of QED.
AB  - We investigate textbook QED in the framework of the exact renormalization group.
      In the strong-coupling region, we study the influence of fluctuation-induced
      photonic and fermionic self-interactions on the nonperturbative running of the
      gauge coupling. Our findings confirm the triviality hypothesis of complete charge
      screening if the ultraviolet cutoff is sent to infinity. Though the Landau pole
      does not belong to the physical coupling domain owing to spontaneous chiral
      symmetry-breaking (chiSB), the theory predicts a scale of maximal UV extension of
      the same order as the Landau pole scale. In addition, we verify that the chiSB
      phase of the theory which is characterized by a light fermion and a Goldstone
      boson also has a trivial Yukawa coupling.

PMID- 15447326
TI  - Pairing fluctuations in trapped fermi gases.
AB  - We examine the contribution of pairing fluctuations to the superfluid order
      parameter for harmonically trapped atomic Fermi gases in the BCS regime. In the
      limit of small systems we consider, both analytically and numerically, their
      space and temperature dependence. We predict a parity effect, i.e., that pairing
      fluctuations show a maximum or a minimum at the center of the trap, depending on
      the value of the last occupied shell being even or odd. We propose to detect
      pairing fluctuations by measuring the density-density correlation function after
      a ballistic expansion of the gas.

PMID- 15447327
TI  - Multipartite entanglement detection in bosons.
AB  - We propose a simple quantum network to detect multipartite entangled states of
      bosons and show how to implement this network for neutral atoms stored in an
      optical lattice. We investigate the special properties of cluster states,
      multipartite entangled states, and superpositions of distinct macroscopic quantum
      states that can be identified by the network.

PMID- 15447328
TI  - Low-scale leptogenesis and soft supersymmetry breaking.
AB  - We investigate the possibility of low-scale leptogenesis in the minimal
      supersymmetric standard model extended with right-handed (s)neutrinos. We
      demonstrate that successful leptogenesis can be easily achieved at a scale as low
      as approximately TeV where lepton number and CP violation comes from soft
      supersymmetry breaking terms. The scenario is shown to be compatible with
      neutrino masses data.

PMID- 15447330
TI  - Transverse structure of nucleon parton distributions from lattice QCD.
AB  - This work presents the first calculation in lattice QCD of three moments of spin
      averaged and spin-polarized generalized parton distributions in the proton. It is
      shown that the slope of the associated generalized form factors decreases
      significantly as the moment increases, indicating that the transverse size of the
      light-cone quark distribution decreases as the momentum fraction of the struck
      parton increases.

PMID- 15447332
TI  - Enhanced electron-capture decay rate of 7Be encapsulated in C60 cages.
AB  - The decay rate of 7Be electron capture was measured in C60 and Be metal with a
      reference method. The half-life of 7Be endohedral C60 ((7)Be@C(60)) and 7Be in Be
      metal (Be metal (7Be)) is found to be 52.68+/-0.05 and 53.12+/-0.05 days,
      respectively. This amounts to a 0.83% difference in electron-capture decay half
      life between (7)Be@C(60) and Be metal (7Be). Our result is a reflection of the
      different electron wave functions for (7)Be@C(60) inside C60 compared to the
      situation when 7Be is in a Be metal.

PMID- 15447329
TI  - First observation and Dalitz analysis of the D0-->K(0)Setapi(0) decay.
AB  - Using 9.0 fb(-1) of integrated luminosity in e(+)e(-) collisions near the
      Upsilon(4S) mass collected with the CLEO II.V detector we report the first
      observation of the decay D0-->K(0)(S)etapi(0). We measure the ratio of branching
      fractions, BR(D0-->K(0)(S)etapi(0))BR / (D0-->K(0)(S)pi(0))=0.46+/-0.07+/-0.06.
      We perform a Dalitz analysis of 155 selected D0-->K(0)(S)etapi(0) candidates and
      find leading contributions from a(0)(980)K(0)(S) and K(*)(892)eta intermediate
      states.

PMID- 15447333
TI  - Axial observables in d-->p--> breakup and the three-nucleon force.
AB  - We have measured three axial polarization observables in d-->p--> breakup with a
      polarized 270 MeV deuteron beam on a polarized proton target. Axial observables
      are zero by parity conservation in elastic scattering but can be easily observed
      in the breakup channel at the present energy. Based on a symmetry argument, the
      sensitivity of these observables to the three-nucleon force might be enhanced.
      Calculations without three-nucleon force are in fair agreement with our
      measurement, indicating that the expected sensitivity of axial observables to the
      three-nucleon force is not confirmed. Including a three-nucleon force in the
      calculation does not improve the agreement with the data.

PMID- 15447334
TI  - Nondipole effects in the photoionization of xe 4d5/2 and 4d3/2: evidence for
      quadrupole satellites.
AB  - Measurements of nondipole parameters in spin-orbit-resolved Xe 4d photoionization
      demonstrate dynamical differences arising from relativistic effects. The
      experimental data do not agree with relativistic random-phase approximation
      calculations of single ionization dipole and quadrupole channels. It is suggested
      that the discrepancy is due to the omission of multiple-excitation quadrupole
      channels, i.e., quadrupole satellite transitions.

PMID- 15447335
TI  - Nuclear charge radii of 8,9Li determined by laser spectroscopy.
AB  - The 2s-->3s transition of (6,7,8,9)Li was studied by high-resolution laser
      spectroscopy using two-photon Doppler-free excitation and resonance-ionization
      detection. Hyperfine structure splittings and isotope shifts were determined with
      precision at the 100 kHz level. Combined with recent theoretical work, the
      changes in the nuclear-charge radii of (8,9)Li were determined. These are now the
      lightest short-lived isotopes for which the charge radii have been measured. It
      is found that the charge radii monotonically decrease with increasing neutron
      number from 6Li to 9Li.

PMID- 15447331
TI  - Observation of a threshold enhancement in the plambda invariant-mass spectrum.
AB  - An enhancement near the m(p)+M(Lambda) mass threshold is observed in the combined
      pLambda and pLambda invariant-mass spectrum from J/psi-->pK(-)Lambda;+c.c.
      decays. It can be fit with an S-wave Breit-Wigner resonance with a mass m=2075+/
      12(stat)+/-5(syst) MeV and a width of Gamma=90+/-35(stat)+/-9(syst) MeV; it can
      also be fit with a P-wave Breit-Wigner resonance. Evidence for a similar
      enhancement is also observed in psi(')-->pK(-)Lambda;+c.c. decays. The analysis
      is based on samples of 5.8x10(7)J/psi and 1.4x10(7)psi(') decays accumulated in
      the BES II detector at the Beijing Electron-Positron Collider.

PMID- 15447336
TI  - Effects of molecular structure on ion disintegration patterns in ionization of O2
      and N2 by short laser pulses.
AB  - We demonstrate that the structure of the outermost orbitals of oxygen and
      nitrogen can be observed in the angular distribution of coincident ion pairs
      generated by the double ionization of these molecules by 8 fs laser pulses. We do
      this by establishing that these ions emerge from well defined excited electronic
      states of O2+2 and N2+2 respectively and that they are produced dominantly
      through a process which involves electron rescattering. The angular distributions
      of the ions from the two targets are very different, reflecting the different
      structures of the outermost orbitals of the two molecules.

PMID- 15447337
TI  - Investigations of positronium formation and destruction using
      3gamma/2gammaannihilation-ratio measurements.
AB  - Positronium (Ps) produced by 4 to 40 eV positrons colliding with Ne, Ar, Kr, CO2,
      and O2 is investigated by measuring the ratio of signals of two gamma rays in
      coincidence resulting from (a) three gamma annihilation of ortho-Ps and (b) two
      annihilation gamma rays due to para-Ps decay and destruction of ortho-Ps at an
      aluminum scattering cell surface. These ratios provide evidence that relates to
      the kinetic energy dependence of ortho-Ps interactions with an aluminum surface,
      the Ps formation potential at this surface, and the fact that Ps is being formed
      with inner orbital electrons for CO2 and O2.

PMID- 15447338
TI  - Phase-space invariants as indicators of the critical behavior of nanoaggregates.
AB  - A phase-space approach is proposed for molecular dynamics simulations, which
      serve as a bridge between detailed descriptions of microscopic world and
      macroscopic properties of matter. The introduction-aside from the angular
      momentum of spatial rotations-of other "hyperangular" momenta (the overall grand
      angular momentum of a cluster of particles and those describing the deformation
      and rearrangement modes) permits one to analyze different degrees of freedom and
      to extract, from simulation data, a kinetic energy partition in terms of phase
      space invariants. Model calculations illustrate how these provide specific
      signatures of critical behavior, such as energy thresholds for openings of
      chaotic pathways in small clusters and for phase transitions in nanoaggregates.

PMID- 15447339
TI  - Nonlinear refraction in photoinduced isotropic state of liquid crystalline
      azobenzenes.
AB  - The photoinduced isotropic state of liquid crystalline azobenzenes exhibits one
      of the strongest nonlinear optical refraction known for isotropic materials. The
      optical nonlinearity of these materials is large in a wide band of the visible
      spectrum and is accompanied with high, over 90%, transmission for red
      wavelengths.

PMID- 15447340
TI  - Observation of discrete quadratic solitons.
AB  - Discrete solitons with two frequency components mutually locked by a quadratic
      nonlinearity have been observed for the first time. Optical experiments have been
      performed in arrays of coupled channel waveguides with tunable cascaded quadratic
      nonlinearity. The tunability was the prerequisite that soliton species with
      different topology could be identified in the same array. Moreover, soliton
      stability has been experimentally probed. Good agreement with theoretical
      predictions was found.

PMID- 15447341
TI  - Desynchronization waves and localized instabilities in oscillator arrays.
AB  - We consider a ring of identical or near-identical coupled periodic oscillators in
      which the connections have randomly heterogeneous strength. We use the master
      stability function method to determine the possible patterns at the
      desynchronization transition that occurs as the coupling strengths are increased.
      We demonstrate Anderson localization of the modes of instability and show that
      such localized instability generates waves of desynchronization that spread to
      the whole array. Similar results should apply to other networks with regular
      topology and heterogeneous connection strengths.

PMID- 15447342
TI  - Dynamical mechanism of anticipating synchronization in excitable systems.
AB  - We analyze the phenomenon of anticipating synchronization of two excitable
      systems with unidirectional delayed coupling which are subject to the same
      external forcing. We demonstrate for different paradigms of excitable system
      that, due to the coupling, the excitability threshold for the slave system is
      always lower than that for the master. As a consequence the two systems respond
      to a common external forcing with different response times. This allows us to
      explain in a simple way the mechanism behind the phenomenon of anticipating
      synchronization in excitable systems.

PMID- 15447343
TI  - Pattern of breakdown of laminar flow into turbulent spots.
AB  - The breakdown into turbulent spots is the least understood stage of the laminar
      turbulent transition process. With cellular-automaton stochastic simulations and
      stability analysis, we show that the pattern of breakdown in boundary-layer flow
      bears a connection to laminar instability and may be reconstructed using
      macroscopic properties of the transition zone, such as persistence times and
      transitional intermittency. We propose experimental tests of our ideas.

PMID- 15447344
TI  - Experimental observation and characterization of the magnetorotational
      instability.
AB  - Differential rotation occurs in conducting flows in accretion disks and planetary
      cores. In such systems, the magnetorotational instability can arise from coupling
      Lorentz and centrifugal forces to cause large radial angular momentum fluxes. We
      present the first experimental observation of the magnetorotational instability.
      Our system consists of liquid sodium between differentially rotating spheres,
      with an imposed coaxial magnetic field. We characterize the observed patterns,
      dynamics, and torque increases, and establish that this instability can occur
      from a hydrodynamic turbulent background.

PMID- 15447345
TI  - Schottky-enabled photoemission in a rf accelerator photoinjector: possible
      generation of ultralow transverse thermal-emittance electron beam.
AB  - We present a clear signature of the Schottky effect in a rf photoinjector using
      photons with energy lower than the Mg cathode work function. This signature is
      manifested by the shift in the rf phase angle for the onset of the detection of
      photoelectrons via single-photon absorption and allows for a reasonable estimate
      of the field enhancement factor. This is a viable method to generate an electron
      beam with very low thermal emittance and thus, a high brightness beam.

PMID- 15447346
TI  - Electro-optic technique with improved time resolution for real-time,
      nondestructive, single-shot measurements of femtosecond electron bunch profiles.
AB  - Electro-optic detection of the Coulomb field of a relativistic electron bunch
      combined with single-shot cross correlation of optical pulses is used to enable
      single-shot measurements of the shape and length of femtosecond electron bunches.
      This method overcomes a fundamental time-resolution limit of previous single-shot
      electro-optic measurements, which arises from the inseparability of time and
      frequency properties of the probing optical pulse. Using this new technique we
      have made real-time measurements of a 50 MeV electron bunch, observing the
      profile of 650 fs FWHM ( approximately 275 fs rms) long bunches.

PMID- 15447347
TI  - First gamma-ray measurements of fusion alpha particles in JET trace tritium
      experiments.
AB  - Gamma-ray spectra from nuclear reactions between fusion-born alpha (alpha)
      particles and Be impurities were measured for the first time in deuterium-tritium
      plasmas in the Joint European Torus. The time dependence of the measured spectra
      allowed the determination of the density evolution of fast alpha particles.
      Correlation between the decay time of the gamma-ray emission and the plasma
      parameters in different plasma scenarios was established. Results are consistent
      with classical slowing down of the alpha particles in discharges with high plasma
      currents and monotonic q-profiles. In low plasma current discharges and in the
      discharges with large on-axis current holes (extreme reversal central magnetic
      shear), the gamma-ray emission decay times are shorter than the classical slowing
      down times, indicating an alpha-particle confinement degradation in such
      discharges in line with theoretical predictions.

PMID- 15447348
TI  - Relativistic Doppler effect: universal spectra and zeptosecond pulses.
AB  - We report on a numerical observation of the train of zeptosecond pulses produced
      by the reflection of a relativistically intense femtosecond laser pulse from the
      oscillating boundary of an overdense plasma because of the Doppler effect. These
      pulses promise to become unique experimental and technological tools since their
      length is of the order of the Bohr radius and the intensity is extremely high
      proportional, variant 10(19) W/cm(2). We present the physical mechanism,
      analytical theory, and direct particle-in-cell simulations. We show that the
      harmonic spectrum is universal: the intensity of nth harmonic scales as 1/n(p)
      for n<4gamma(2), where gamma is the largest gamma factor of the electron fluid
      boundary, and p=3 and p=5/2 for the broadband and quasimonochromatic laser
      pulses, respectively.

PMID- 15447349
TI  - Postponement of saturation of the Richtmyer-Meshkov instability in a convergent
      geometry.
AB  - Strongly shocked cylindrically convergent implosions were conducted on the OMEGA
      laser. The directly driven targets consist of a low-density foam core and an
      embedded aluminum shell covered by an epoxy ablator. The outer surface of the
      aluminum shell has imposed single-mode perturbations with wave numbers k=0.08,
      0.25, and 0.7 (rad/microm) and initial amplitudes eta(0)/lambda=0.013, 0.04 and
      0.11. The perturbation growth rate is found to scale with k and, in our
      convergent geometry, no evidence of saturation for eta/lambda as large as 5 is
      observed.

PMID- 15447350
TI  - Importance of shear in the bcc-to-hcp transformation in iron.
AB  - Iron shows a pressure-induced martensitic phase transformation from the ground
      state ferromagnetic bcc phase to a nonmagnetic hcp phase at approximately 13 GPa.
      The exact transformation pressure (TP) and pathway are not known. Here we present
      a multiscale model containing a quantum-mechanics-based multiwell energy function
      accounting for the bcc and hcp phases of Fe and a construction of kinematically
      compatible and equilibrated mixed phases. This model suggests that shear stresses
      have a significant influence on the bcc<-->hcp transformation. In particular, the
      presence of modest shear accounts for the scatter in measured TPs. The formation
      of mixed phases also provides an explanation for the observed hysteresis in TP.

PMID- 15447351
TI  - Formation and structure of a dense octahedral glass.
AB  - We have performed in situ x-ray and neutron-diffraction measurements, and
      molecular dynamics simulations, of GeO2, an archetypal network-forming glass
      under pressure. Below 5 GPa, additional atoms encroaching on the first
      tetrahedral shell are seen to be a precursor of local coordination change.
      Between 6 and 10 GPa, we observe structures with a constant average coordination
      of approximately 5, indicating a new metastable, intermediate form of the glass.
      At 15 GPa, the structure of a fully octahedral glass has been measured. This
      structure is not retained upon decompression and, therefore, must be studied in
      situ.

PMID- 15447352
TI  - Structure and mechanical properties of high-porosity macroscopic agglomerates
      formed by random ballistic deposition.
AB  - We present experimental results on the mechanical properties of macroscopic
      agglomerates formed by ballistic hit-and-stick deposition. The agglomerates,
      produced with a new experimental method, consist of monodisperse SiO2 spheres
      with 1.5 microm diameter and have a volume filling factor of phi=0.15, matching
      very closely the theoretical value for random ballistic deposition. They are
      mechanically stable against unidirectional compression of up to 500 Pa. For
      pressures above that value, the volume filling factor increases to a maximum of
      phi=0.33 for pressures above 10(5) Pa. The tensile strength of slightly
      compressed samples (phi=0.2) is 1000 Pa.

PMID- 15447353
TI  - Heterogeneous dynamics of coarsening systems.
AB  - We show by means of experiments, theory, and simulations that the slow dynamics
      of coarsening systems displays dynamic heterogeneity similar to that observed in
      glass-forming systems. We measure dynamic heterogeneity via novel multipoint
      functions which quantify the emergence of dynamic, as opposed to static,
      correlations of fluctuations. Experiments are performed on a coarsening foam
      using time-resolved correlation, a recently introduced light scattering method.
      Theoretically we study the Ising model, and present exact results in one
      dimension, and numerical results in two dimensions. For all systems the same
      dynamic scaling of fluctuations with domain size is observed.

PMID- 15447354
TI  - Constrained deformation of a confined solid: anomalous failure by nucleation of
      smectic bands.
AB  - We report results of computer simulations of the deformation and failure behavior
      of a thin crystalline strip of "hard disks" in two dimensions confined within a
      quasi-one-dimensional "hard-wall" channel of fixed width corresponding to a few
      disk diameters. Starting from a commensurate triangular solid, stretching the
      strip along its length introduces a rectangular distortion. This, beyond a
      critical strain, leads to failure of the solid by "phase separation" into
      alternating bands of solid and smectic-like phases. The critical strain is
      inversely proportional to the channel width, i.e., thinner strips are stronger.
      The large plastic deformation which precedes failure is observed to be
      reversible.

PMID- 15447356
TI  - Optical response of the copper surface to carbon monoxide deposition.
AB  - The optical response of the Cu surface upon CO deposition is investigated from
      the clean Cu(110) to the reconstructed CO/Cu(110)-p(2x1) geometry through ab
      initio electronic structure calculations. We ascribe the relevant structures in
      the calculated reflectance anisotropy spectrum of the reconstructed phase to the
      persistence of surface states transitions. These are excited by light polarized
      along the direction perpendicular to the one found at the clean surface. We
      devise a simple model for the evolution of the optical response in the adsorption
      process, identifying three different regimes. The impurity regime, at very low
      coverages, is characterized by a critical coverage that enhances the actual one
      by a factor of approximately 30, close to the value estimated experimentally.

PMID- 15447355
TI  - Novel water overlayer growth on Pd(111) characterized with scanning tunneling
      microscopy and density functional theory.
AB  - Scanning tunneling microscopy (STM) images of water submonolayers on Pd(111)
      reveal quasiperiodic and isolated adclusters with internal structure that would
      ordinarily be ascribed to icelike puckered hexagonal units. However, density
      functional theory and STM simulations contradict this conventional picture,
      showing instead that the water adlayers are composed mainly of flat-lying
      molecules arranged in planar water hexagons. A new rule for two dimensional (2D)
      water growth is offered that generates the structures observed experimentally
      from planar hexamer units.

PMID- 15447357
TI  - Borderline magic clustering: the fabrication of tetravalent Pb cluster arrays on
      Si(111)-(7x7) surfaces.
AB  - Well-ordered arrays of identical Pb clusters have been fabricated on a Si(111)
      (7x7) substrate by the temperature-mediated surface clustering method.
      Interestingly, these clusters can easily transform into other forms when the
      growth temperature deviates slightly from the optimal values. In accord with
      experiments, first-principle total-energy calculations reveal several cluster
      structures centered on a mixed cluster model involving surface Pb and Si
      exchange. This borderline Pb/Si(111) system provides a unique, controlled way to
      study surface magic cluster formation and breakup dynamics.

PMID- 15447358
TI  - Microscopic view of charge injection in an organic semiconductor.
AB  - We have measured the chemical potential and capacitance in a disordered organic
      semiconductor by electric force microscopy, following the electric field and
      interfacial charge density microscopically as the semiconductor undergoes a
      transition from Ohmic to space-charge limited conduction. Electric field and
      charge density at the metal-organic interface are inferred from the chemical
      potential and current. The charge density at this interface increases with
      electric field much faster than is predicted by the standard diffusion-limited
      thermionic emission theories.

PMID- 15447359
TI  - The steady state of heterogeneous catalysis, studied by first-principles
      statistical mechanics.
AB  - The turnover frequency of the catalytic oxidation of CO at RuO2(110) was
      calculated as a function of temperature and partial pressures using ab initio
      statistical mechanics. The underlying energetics of the gas-phase molecules,
      dissociation, adsorption, surface diffusion, surface chemical reactions, and
      desorption were obtained by all-electron density-functional theory. The resulting
      CO2 formation rate [in the full (T,p(CO),p(O2)) space], the movies displaying the
      atomic motion and reactions over times scales from picoseconds to seconds, and
      the statistical analyses provide insight into the concerted actions ruling
      heterogeneous catalysis and open thermodynamic systems in general.

PMID- 15447360
TI  - Structural relaxations in electronically excited poly(para-phenylene).
AB  - Structural relaxations in electronically excited poly(para-phenylene) are studied
      using many-body perturbation theory and density-functional-theory methods. A
      sophisticated description of the electron-hole interaction is required to
      describe the excitonic energies, but the associated structural relaxations can be
      obtained quite accurately within a constrained density-functional-theory
      approach. We find that the structural relaxations in the low-energy excitonic
      states extend over about eight monomers, leading to an energy reduction of 0.22
      eV and a Stokes shift of 0.40 eV.

PMID- 15447361
TI  - Spin dynamics and charge order in beta-Na1/3V2O5.
AB  - We present detailed electron-spin resonance investigations on single crystals of
      the one-dimensional vanadium-oxide bronze beta-Na(1/3)V2O5. From the angular
      dependence of the g value it can be concluded that the electrons are primarily
      located on the V1 zigzag chains. The anisotropy of the linewidth, which is
      determined by the intrachain symmetric anisotropic exchange interaction, favors
      statistic electron distribution in the metallic and blockwise charge-order in the
      insulating phase. The temperature dependence of the linewidth indicates the
      opening of a charge gap at the metal-to-insulator transition at T(MI)=132 K.

PMID- 15447362
TI  - Adiabatic pumping in the mixed-valence and Kondo regimes.
AB  - We investigate adiabatic pumping through a quantum dot with a single level in the
      mixed-valence and Kondo regimes using the slave boson mean field approximation.
      The pumped current is driven by a gauge potential due to time-dependent tunneling
      barriers as well as by the modulation of the Friedel phase. The sign of the
      former contribution depends on the strength of the Coulomb interaction. Under
      finite magnetic fields, the separation of the spin and charge currents peculiar
      to the Kondo effect occurs.

PMID- 15447363
TI  - Fano factor reduction on the 0.7 conductance structure of a ballistic one
      dimensional wire.
AB  - We have measured the nonequilibrium current noise in a ballistic one-dimensional
      wire which exhibits an additional conductance plateau at 0.7x2e(2)/h. The Fano
      factor shows a clear reduction on the 0.7 structure, and eventually vanishes upon
      applying a strong parallel magnetic field. These results provide experimental
      evidence that the 0.7 structure is associated with two conduction channels that
      have different transmission probabilities.

PMID- 15447364
TI  - Direct observation of ferromagnetic spin polarization in gold nanoparticles.
AB  - We report the first direct observation of ferromagnetic spin polarization of Au
      nanoparticles with a mean diameter of 1.9 nm using x-ray magnetic circular
      dichroism (XMCD). Owing to the element selectivity of XMCD, only the gold
      magnetization is explored. Magnetization of gold atoms as estimated by XMCD shows
      a good agreement with results obtained by conventional magnetometry. This
      evidences intrinsic spin polarization in nanosized gold.

PMID- 15447365
TI  - Vortex clusters in quantum dots.
AB  - We study electronic structures of two-dimensional quantum dots in strong magnetic
      fields using mean-field density-functional theory and exact diagonalization. Our
      numerically accurate mean-field solutions show a reconstruction of the uniform
      density electron droplet when the magnetic field flux quanta enter one by one the
      dot in stronger fields. These quanta correspond to repelling vortices forming
      polygonal clusters inside the dot. We find similar structures in the exact
      treatment of the problem by constructing a conditional operator for the analysis.
      We discuss important differences and limitations of the methods used.

PMID- 15447366
TI  - Metallic adhesion in atomic-size junctions.
AB  - We report high resolution simultaneous measurements of electrical conductance and
      force gradient between two sharp gold tips as their separation is varied from the
      tunneling distance to atomic-size contact. The use of atomically sharp tips
      minimizes van der Waals interaction, making it possible to identify the short
      range metallic adhesion contribution to the total force.

PMID- 15447367
TI  - Amphoteric and controllable doping of carbon nanotubes by encapsulation of
      organic and organometallic molecules.
AB  - By using first principles calculations, we show that fine tuning of both p- and n
      type doping can be realized on single-wall carbon nanotubes (SWNTs) by tuning the
      electron affinity or ionization potential of the organic and organometallic
      molecules encapsulated inside SWNTs. This novel type of SWNT-based material
      offers great promise for molecular electronics because of its air stability,
      synthetic simplicity and the abundance of organic and organometallic molecules.

PMID- 15447368
TI  - Excitation of spin waves in superconducting ferromagnets.
AB  - This Letter presents a theoretical analysis of propagation of spin waves in a
      superconducting ferromagnet. The surface impedance was calculated for the case
      when the magnetization is normal to the sample surface. We found the frequencies
      at which the impedance and the power absorption have singularities related to the
      spin-wave propagation, and determined the form of these singularities. With a
      suitable choice of parameters, there is a frequency interval in which two
      propagating spin waves of the same circular polarization are generated, one of
      them having a negative group velocity.

PMID- 15447369
TI  - Strong correlations in electron doped phthalocyanine conductors near half
      filling.
AB  - We propose that electron doped nontransition metal phthalocyanines such as ZnPc
      and MgPc, similar to those very recently reported, should constitute novel
      strongly correlated metals. Because of orbital degeneracy, Jahn-Teller coupling,
      and Hund's rule exchange, and with a large on-site Coulomb repulsion, these
      molecular conductors should display, particularly near half filling at two
      electrons/molecule, very unconventional properties, including Mott insulators,
      strongly correlated superconductivity, and other intriguing phases.

PMID- 15447370
TI  - Coupling of the B1g phonon to the antinodal electronic states of
      Bi2Sr2Ca0.92Y0.08Cu2O8+delta.
AB  - Angle-resolved photoemission spectroscopy on optimally doped
      Bi(2)Sr(2)Ca(0.92)Y(0.08)Cu(2)O(8+delta) uncovers a coupling of the electronic
      bands to a 40 meV mode in an extended k-space region away from the nodal
      direction, leading to a new interpretation of the strong renormalization of the
      electronic structure seen in Bi2212. Phenomenological agreements with neutron and
      Raman experiments suggest that this mode is the B(1g) oxygen bond-buckling
      phonon. A theoretical calculation based on this assignment reproduces the
      electronic renormalization seen in the data.

PMID- 15447371
TI  - Anisotropic electron-phonon interaction in the cuprates.
AB  - We explore manifestations of electron-phonon coupling on the electron spectral
      function for two phonon modes in the cuprates exhibiting strong renormalizations
      with temperature and doping. Applying simple symmetry considerations and
      kinematic constraints, we find that the out-of-plane, out-of-phase O buckling
      mode (B(1g)) involves small momentum transfers and couples strongly to electronic
      states near the antinode while the in-plane Cu-O breathing modes involve large
      momentum transfers and couples strongly to nodal electronic states. Band
      renormalization effects are found to be strongest in the superconducting state
      near the antinode, in full agreement with angle-resolved photoemission
      spectroscopy data.

PMID- 15447372
TI  - Kink in the dispersion of layered strontium ruthenates.
AB  - We present detailed energy dispersions near the Fermi level along the high
      symmetry line GammaX on the monolayer and bilayer strontium ruthenates Sr2RuO4
      and Sr3Ru2O7, determined by high-resolution angle-resolved photoemission
      spectroscopy. A kink in the dispersion is clearly shown for the both ruthenates.
      The energy position of the kink and the slope in the low-energy part near the
      Fermi level are almost identical between them, whereas the dispersion in the high
      energy part varies, like the behavior of the kink for the cuprate
      superconductors.

PMID- 15447373
TI  - Ferromagnetism mediated by few electrons in a semimagnetic quantum dot.
AB  - A (II,Mn)VI diluted magnetic semiconductor quantum dot with an integer number of
      electrons controlled with a gate voltage is considered. We show that a single
      electron is able to induce a collective spontaneous magnetization of the Mn
      spins, overcoming the short range antiferromagnetic interactions, at a
      temperature order of 1 K, 2 orders of magnitude above the ordering temperature in
      bulk. The magnetic behavior of the dot depends dramatically on the parity of the
      number of electrons in the dot.

PMID- 15447374
TI  - Magnetic long-range order induced by quantum relaxation in single-molecule
      magnets.
AB  - Can magnetic interactions between single-molecule magnets (SMMs) in a crystal
      establish long-range magnetic order at low temperatures deep in the quantum
      regime, where the only electron spin fluctuations are due to incoherent magnetic
      quantum tunneling (MQT)? Put inversely: can MQT provide the temperature dependent
      fluctuations needed to destroy the ordered state above some finite T(c), although
      it should basically itself be a T-independent process? Our experiments on two
      novel Mn4 SMMs provide a positive answer to the above, showing at the same time
      that MQT in the SMMs has to involve spin-lattice coupling at a relaxation rate
      equaling that predicted and observed recently for nuclear-spin-mediated quantum
      relaxation.

PMID- 15447375
TI  - Tunneling anisotropic magnetoresistance: a spin-valve-like tunnel
      magnetoresistance using a single magnetic layer.
AB  - We introduce a new class of spintronic devices in which a spin-valve-like effect
      results from strong spin-orbit coupling in a single ferromagnetic layer rather
      than from injection and detection of a spin-polarized current by two coupled
      ferromagnets. The effect is observed in a normal-metal-insulator-ferromagnetic
      semiconductor tunneling device. This behavior is caused by the interplay of the
      anisotropic density of states in (Ga,Mn)As with respect to the magnetization
      direction and the two-step magnetization reversal process in this material.

PMID- 15447376
TI  - Formation of finite antiferromagnetic clusters and the effect of electronic phase
      separation in Pr0.5Ca0.5Mn0.975Al0.025O3.
AB  - We report the first experimental evidence of a magnetic phase arising due to the
      thermal blocking of antiferromagnetic clusters in the weakened charge and orbital
      ordered system Pr0.5Ca0.5Mn0.975Al0.025O3. The third order susceptibility
      (chi(3)) is used to differentiate this transition from a spin- or cluster-glass
      like freezing mechanism. These clusters are found to be mesoscopic and robust to
      electronic phase separation which only enriches the antiphase domain walls with
      holes at the cost of the bulk, without changing the size of these clusters.

PMID- 15447377
TI  - Magnetic stripe domains in coupled magnetic sandwiches.
AB  - Magnetic stripe domains in the spin reorientation transition region are
      investigated in (Fe/Ni)/Cu(001) and Co/Cu/(Fe/Ni)/Cu(001) using photoemission
      electron microscopy. For (Fe/Ni)/Cu(001), the stripe domain width decreases
      exponentially as the Fe/Ni film approaches the spin reorientation transition
      point. For Co/Cu/(Fe/Ni)/Cu(001), the Fe/Ni stripe orientation is aligned with
      the Co in-plane magnetization, and the stripe domain width decreases
      exponentially with increasing the interlayer coupling between the Fe/Ni and Co
      films. By considering magnetic stripes within an in-plane magnetic field, we
      reveal a universal dependence of the stripe domain width on the magnetic
      anisotropy and on the interlayer coupling.

PMID- 15447378
TI  - Photoinduced structural instability of the InP (110)-(1x1) surface.
AB  - A scanning tunneling microscopy study reveals the removal of P and In atoms at
      intrinsic surface sites of InP (110)-(1x1) through an electronic mechanism under
      ns-laser excitation. Femtosecond nonresonant ionization spectroscopy detects
      desorption of P and In atoms associated directly with the bond rupture, and shows
      their translational energies characteristic of electronic bong breaking. The rate
      of P-atom removal is 4 times higher than that of In-atom removal, revealing a
      prominent species-dependent effect of structural instability under electronic
      excitation on semiconductor surfaces.

PMID- 15447379
TI  - Ultrafast manipulation of antiferromagnetism of NiO.
AB  - Photoexcitation of antiferromagnetic NiO leads to ultrafast reorientation of Ni2+
      spins due to change of the magnetic anisotropy. Recovery of the magnetic ground
      state occurs as coherent oscillation of the antiferromagnetic order parameter
      between hard- and easy-axis states manifesting itself as quantum beating. The
      coherence time is approximately 1 ns with the beating frequency being determined
      by the anisotropy energy.

PMID- 15447380
TI  - Ordered droplet structures at the liquid crystal surface and elastic-capillary
      colloidal interactions.
AB  - We demonstrate a variety of ordered patterns, including hexagonal structures and
      chains, formed by colloidal particles (droplets) at the free surface of a nematic
      liquid crystal (LC). The surface placement introduces a new type of particle
      interaction as compared to particles entirely in the LC bulk. Namely, director
      deformations caused by the particles lead to distortions of the interface and
      thus to capillary attraction. The elastic-capillary coupling is strong enough to
      remain relevant even at the micron-scale when its buoyancy-capillary counterpart
      becomes irrelevant.

PMID- 15447381
TI  - Stripe formation in differentially forced binary systems.
AB  - We consider pattern formation in periodically forced binary systems. In
      particular, we focus on systems in which the two species are differentially
      forced, one being accelerated with respect to the other. Using a continuum model
      consisting of two isothermal ideal gases which interact via a frictional force we
      demonstrate analytically that stripes form spontaneously above a critical forcing
      amplitude. The wavelength of the stripes is found to be close to the wavelength
      of sound in the limit of small viscosity. The results are confirmed numerically.
      We suggest that the same mechanism may contribute to the formation of stripes in
      experiments on horizontally oscillated granular mixtures.

PMID- 15447382
TI  - Signal propagation and failure in discrete autocrine relays.
AB  - A mechanistic model of discrete one-dimensional arrays of autocrine cells
      interacting via diffusible signals is investigated. Under physiologically
      relevant assumptions, the model is reduced to a system of ordinary differential
      equations for the intracellular variables, with a particular, biophysically
      derived type of long-range coupling between cells. Exact discrete traveling wave
      and static kink solutions are obtained in the model with sharp threshold
      nonlinearity. It is argued that the considered mechanism may be used extensively
      for transmission of information in tissues during homeostasis and development.

PMID- 15447383
TI  - Elastic properties of a single-stranded charged homopolymeric ribonucleotide.
AB  - We have investigated the elastic properties of poly(U), homopolymeric single
      stranded RNA molecules that lack any base pairing and stacking interactions and
      conform to a random-coil structure. Using single-molecule stretching experiments
      we show that the elastic properties are described by a wormlike chain model for
      polymer elasticity rather than by a freely jointed chain model as is commonly
      used for single-stranded DNA. At low [Na+], introduction of a scale-dependent
      persistence length is required to account for electrostatic contributions.

PMID- 15447384
TI  - Gating-by-tilt of mechanically sensitive membrane channels.
AB  - We propose an alternative mechanism for the gating of biological membrane
      channels in response to membrane tension that involves a change in the slope of
      the membrane near the channel. Under biological membrane tensions we show that
      the energy difference between the closed (tilted) and open (untilted) states can
      far exceed k(B)T and is comparable to what is available under simple dilational
      gating. Recent experiments demonstrate that membrane leaflet asymmetries
      (spontaneous curvature) can strongly affect the gating of some channels. Such a
      phenomenon would be easier to explain under gating-by-tilt, given its novel
      intrinsic sensitivity to such asymmetry.

PMID- 15447385
TI  - Quantifying self-organization with optimal predictors.
AB  - Despite broad interest in self-organizing systems, there are few quantitative,
      experimentally applicable criteria for self-organization. The existing criteria
      all give counter-intuitive results for important cases. In this Letter, we
      propose a new criterion, namely, an internally generated increase in the
      statistical complexity, the amount of information required for optimal prediction
      of the system's dynamics. We precisely define this complexity for spatially
      extended dynamical systems, using the probabilistic ideas of mutual information
      and minimal sufficient statistics. This leads to a general method for predicting
      such systems and a simple algorithm for estimating statistical complexity. The
      results of applying this algorithm to a class of models of excitable media
      (cyclic cellular automata) strongly support our proposal.

PMID- 15447386
TI  - Comment on "temperature-dependent fermi gap opening in the c(6x4)-C60/Ag001 two
      dimensional superstructure".

PMID- 15447388
TI  - Soliton trains in Bose-Fermi mixtures.
AB  - We theoretically consider the formation of bright solitons in a mixture of Bose
      and Fermi degenerate gases. While we assume the forces between atoms in a pure
      Bose component to be effectively repulsive, their character can be changed from
      repulsive to attractive in the presence of fermions provided the Bose and Fermi
      gases attract each other strongly enough. In such a regime the Bose component
      becomes a gas of effectively attractive atoms. Hence, generating bright solitons
      in the bosonic gas is possible. Indeed, after a sudden increase of the strength
      of attraction between bosons and fermions (realized by using a Feshbach resonance
      technique or by firm radial squeezing of both samples) soliton trains appear in
      the Bose-Fermi mixture.

PMID- 15447389
TI  - Multiple domain formation induced by modulation instability in two-component Bose
      Einstein condensates.
AB  - The dynamics of multiple domain formation caused by the modulation instability of
      two-component Bose-Einstein condensates in an axially symmetric trap are studied
      by numerically integrating the coupled Gross-Pitaevskii equations. The modulation
      instability induced by the intercomponent mean-field coupling occurs in the out
      of-phase fluctuation of the wave function and leads to the formation of multiple
      domains that alternate from one domain to another, where the phase of one
      component jumps across the density dips where the domains of the other exist.
      This behavior is analogous to a soliton train, which explains the origin of the
      long lifetime of the spin domains observed by Miesner et al. [Phys. Rev. Lett.
      82, 2228 (1999)]].

PMID- 15447390
TI  - Experimental demonstration of continuous variable quantum erasing.
AB  - We experimentally demonstrate the concept of continuous variable quantum erasing.
      The amplitude quadrature of the signal state is labeled to another state via a
      quantum nondemolition interaction, leading to a large uncertainty in the
      determination of the phase quadrature due to the inextricable complementarity of
      the two observables. We show that by erasing the amplitude quadrature information
      we are able to recover the phase quadrature information of the signal state.

PMID- 15447391
TI  - Quantitative comparison between theoretical predictions and experimental results
      for the BCS-BEC crossover.
AB  - Theoretical predictions for the Bardeen-Cooper-Schrieffer-Bose-Einstein
      condensation crossover of trapped Fermi atoms are compared with recent
      experimental results for the density profiles of 6Li. The calculations rest on a
      single theoretical approach that includes pairing fluctuations beyond mean-field.
      Excellent agreement with experimental results is obtained. Theoretical
      predictions for the zero-temperature chemical potential and gap at the unitarity
      limit are also found to compare extremely well with Quantum Monte Carlo
      simulations and with recent experimental results.

PMID- 15447392
TI  - Physical limits to communication.
AB  - The limits posed by physics to the quantity of information that can be
      transmitted with a certain amount of power are investigated. The same ultimate
      limits are found for transmission of information encoded using matter and
      massless fields.

PMID- 15447393
TI  - Scaling ion trap quantum computation through fast quantum gates.
AB  - We propose a method to achieve scalable quantum computation based on fast quantum
      gates on an array of trapped ions, without the requirement of ion shuttling.
      Conditional quantum gates are obtained for any neighboring ions through spin
      dependent acceleration of the ions from periodic photon kicks. The gates are
      shown to be robust to influence all the other ions in the array and insensitive
      to the ions' temperature.

PMID- 15447394
TI  - Time reversal and charge echo in an electron gas.
AB  - Apart from subtle violations of CP symmetry by the weak interactions, the basic
      laws of physics are time-reversal invariant. Nevertheless, in the macroscopic
      world, time has a very definite direction, or arrow. Given that the dynamics of a
      closed system are time-reversal invariant, the arrow of time is introduced
      through boundary or initial conditions. In this Letter it is argued that if the
      Hamiltonian for a system, H, has the property THT(-1)=-H for a unitary
      transformation T, then the system can, in principle, be made to evolve backward
      in time. The prototype of this sort of behavior is the spin echo. Calculations
      for a single-band tight-binding model suggest that it may be possible to observe
      the electronic counterpart, or charge echo.

PMID- 15447396
TI  - Two-loop Sudakov form factor in a theory with a mass gap.
AB  - The two-loop Sudakov form factor is computed in a U(1) model with a massive gauge
      boson and a U(1)xU(1) model with mass gap. We analyze the result in the context
      of hard and infrared evolution equations and establish a matching procedure which
      relates the theories with and without mass gap, setting the stage for the
      complete calculation of the dominant two-loop corrections to electroweak
      processes at high energy.

PMID- 15447395
TI  - Evidence for an oscillatory signature in atmospheric neutrino oscillations.
AB  - Muon neutrino disappearance probability as a function of neutrino flight length L
      over neutrino energy E was studied. A dip in the L/E distribution was observed in
      the data, as predicted from the sinusoidal flavor transition probability of
      neutrino oscillation. The observed L/E distribution constrained nu(micro)<-
      >nu(tau) neutrino oscillation parameters; 1.9x10(-3)<Deltam(2)<3.0x10(-3) eV(2)
      and sin((2)2theta>0.90 at 90% confidence level.

PMID- 15447398
TI  - Measurement of the beta-nu correlation using magneto-optically trapped 21Na.
AB  - The beta-neutrino correlation coefficient, a(betanu), in 21Na is inferred from
      detecting the beta(+) and low-energy recoil daughter nucleus. 21Na is produced at
      the 88-Inch Cyclotron at Lawrence Berkeley National Laboratory and 800 000 atoms
      are maintained in a magneto-optical trap. From the measured time of flight of
      recoil ions in the presence of a drift electric field, we find a(betanu)=0.5243+/
      0.0091. There may be a dependence on the trapped atom population. This and other
      systematic uncertainties are discussed.

PMID- 15447397
TI  - Nuclear stopping in Au+Au collisions at square root of S(NN)=200 GeV.
AB  - Transverse momentum spectra and rapidity densities, dN/dy, of protons,
      antiprotons, and net protons (p-p) from central (0%-5%) Au+Au collisions at
      square root of S(NN)=200 GeV were measured with the BRAHMS experiment within the
      rapidity range 0</=y</=3. The proton and antiproton dN/dy decrease from
      midrapidity to y=3. The net-proton yield is roughly constant for y<1 at dN/dy
      approximately 7, and increases to dN/dy approximately 12 at y approximately 3.
      The data show that collisions at this energy exhibit a high degree of
      transparency and that the linear scaling of rapidity loss with rapidity observed
      at lower energies is broken. The energy loss per participant nucleon is estimated
      to be 73+/-6 GeV.

PMID- 15447399
TI  - Regular and chaotic vibrations of deformed nuclei with increasing gamma rigidity.
AB  - We study classical trajectories corresponding to L=0 vibrations in the geometric
      collective model of nuclei with stable axially symmetric quadrupole deformations.
      It is shown that with increasing stability against the onset of triaxiality the
      dynamics passes between a fully regular and semiregular limiting regime. In the
      transitional region, an interplay of chaotic and regular motions results in
      complex oscillatory dependence of the regular phase space on the Hamiltonian
      parameter and energy.

PMID- 15447400
TI  - Quantum calculations of Coulomb reorientation for sub-barrier fusion.
AB  - Classical mechanics and time dependent Hartree-Fock (TDHF) calculations of heavy
      ions collisions are performed to study the rotation of a deformed nucleus in the
      Coulomb field of its partner. This reorientation is shown to be independent of
      the charges and relative energy of the partners. It only depends upon the
      deformations and inertias. TDHF calculations predict an increase by 30% of the
      induced rotation due to quantum effects while the nuclear contribution seems
      negligible. This reorientation modifies strongly the fusion cross section around
      the barrier for light deformed nuclei on heavy collision partners. For such
      nuclei a hindrance of the sub-barrier fusion is predicted.

PMID- 15447401
TI  - Coherence-preserving trap architecture for long-term control of giant Ryberg
      atoms.
AB  - We present a way to trap a single Rydberg atom, make it long-lived, and preserve
      an internal coherence over time scales reaching into the minute range. We propose
      to trap using carefully designed electric fields, to inhibit the spontaneous
      emission in a nonresonant conducting structure, and to maintain the internal
      coherence through a tailoring of the atomic energies using an external microwave
      field. We thoroughly identify and account for many causes of imperfection in
      order to verify at each step the realism of our proposal.

PMID- 15447402
TI  - Cavity QED with quantized center of mass motion.
AB  - We investigate the quantum fluctuations of a single atom in a weakly driven
      cavity, where the center of mass motion of the atom is quantized in one
      dimension. We present analytic results for the second order intensity correlation
      function g((2))(tau) and the intensity-field correlation function h(theta)(tau),
      for transmitted light in the weak driving field limit. We find that the coupling
      of the center of mass motion to the intracavity field mode can be deleterious to
      nonclassical effects in photon statistics and field-intensity correlations, and
      compare the use of trapped atoms in a cavity to atomic beams.

PMID- 15447403
TI  - All-fiber format compression of frequency chirped pulses in air-guiding photonic
      crystal fibers.
AB  - Air-cored, photonic band-gap crystal fibers exhibiting low nonlinearity and
      anomalous chromatic dispersion in spectral ranges inaccessible to conventional
      fibers can be used in the realization of all-fiber-format pulse compressors with
      unprecedented peak powers and wavelength diversity. Linear compression of
      inherently chirped and prestretched pulses by factors ranging from 20 to 80
      around 1.0 and 1.5 microm have allowed generation of pulses as short as 163 fs.
      The results show that totally integrated femtosecond fiber laser sources can be
      realized throughout the visible and near-infrared and point to the possibility of
      megawatt peak and tens of watt average in-fiber power levels.

PMID- 15447404
TI  - Grating-mediated waveguiding.
AB  - We propose a method of optical waveguiding, which relies on Bragg diffractions
      from a 1D grating that gives rise to waveguiding in the direction normal to the
      grating wave vector. The waveguide structure consists of a shallow 1D grating
      that has a bell- or trough-shaped amplitude in the confinement direction.
      Finally, we provide an experimental proof of the concept for this mechanism.

PMID- 15447405
TI  - Whispering gallery modes in nanosized dielectric resonators with hexagonal cross
      section.
AB  - The size dependence of whispering gallery modes in dielectric resonators with
      hexagonal cross section has been observed within the visible spectral range for
      cavity diameters comparable to the light wavelength. As a model system single,
      tapered, high aspect ratio zinc oxide nanoneedles were analyzed. They enable
      systematic investigations as a function of the resonator diameter down to the
      nanometer regime. A simple plane wave interference model without free parameter
      describes the spectral positions and the linewidths of the modes in good
      agreement with the experiment.

PMID- 15447406
TI  - Aging transition and universal scaling in oscillator networks.
AB  - Self-sustained oscillators may turn non-self-oscillatory as a result of some kind
      of deterioration, which we call aging for simplicity. We discuss the effect of
      aging on the behavior of globally and diffusively coupled oscillators which are
      either all periodic or chaotic. It is shown that at a certain level of aging,
      macroscopic oscillation stops in a way which depends on the coupling strength. A
      universal scaling function to describe it is analytically derived and numerically
      verified.

PMID- 15447407
TI  - Chemical instability induced by a shear flow.
AB  - We predict a new type of instability induced by shear flow in chemical systems. A
      homogeneous steady state solution of a reaction-diffusion system loses stability
      in a Poiseuille flow. The instability appears as the speed of the flow increases
      beyond a certain threshold. This results in a steady pattern moving with the
      average fluid velocity. The chemical reaction consists of two species (activator
      and inhibitor) moving with identical velocities. Contrary to Turing's
      instability, the pattern arises when the activator has a higher diffusivity than
      the inhibitor.

PMID- 15447408
TI  - Structure of the magnetic reconnection diffusion region from four-spacecraft
      observations.
AB  - Magnetic reconnection leads to energy conversion in large volumes in space but is
      initiated in small diffusion regions. Because of the small sizes of the diffusion
      regions, their crossings by spacecraft are rare. We report four-spacecraft
      observations of a diffusion region encounter at the Earth's magnetopause that
      allow us to reliably distinguish spatial from temporal features. We find that the
      diffusion region is stable on ion time and length scales in agreement with
      numerical simulations. The electric field normal to the current sheet is balanced
      by the Hall term in the generalized Ohm's law, E(n) approximately jxB/ne.n, thus
      establishing that Hall physics is dominating inside the diffusion region. The
      reconnection rate is fast, approximately 0.1. We show that strong parallel
      currents flow along the separatrices; they are correlated with observations of
      high-frequency Langmuir/upper hybrid waves.

PMID- 15447409
TI  - Resistive wall mode in collisionless quasistationary plasmas.
AB  - The stability analysis of the n=1 resistive wall mode is carried out for a
      simplified model of collisionless tokamak plasma. It is found that the trapped
      particle compressibility and the resonance between the mode and the precession
      drift frequency lead to a significant improvement of the beta stability limits.
      It is shown that, within the frame of the simplified model, the resistive wall
      mode can be fully suppressed and the plasma can be stable up to the wall beta
      limits for a slow plasma rotation.

PMID- 15447410
TI  - Shear Alfven wave perpendicular propagation from the kinetic to the inertial
      regime.
AB  - We report on observations of shear Alfven waves radiated from a source of small
      transverse size, and the subsequent radial confinement of wave magnetic field
      energy within a cylindrical plasma. The radius of confinement lies between the
      kinetic regime of the bulk plasma and the inertial regime at the plasma edge;
      this radius is found to be a function of wave frequency. Numerical calculations
      using kinetic theory predict a zero in the perpendicular group velocity at a
      radius which varies in accord with the observations. An analytic expression for
      the perpendicular group velocity (valid for small perpendicular wave numbers) is
      given in the vicinity of the zero crossing.

PMID- 15447411
TI  - Nonlinear evolution of the lower-hybrid drift instability in a current sheet.
AB  - The lower-hybrid drift instability is simulated in an ion-scale current sheet
      using a fully kinetic approach with values of the ion to electron mass ratio up
      to m(i)/m(e)=1836. Although the instability is localized on the edge of the
      layer, the nonlinear development increases the electron flow velocity in the
      central region resulting in a strong bifurcation of the current density and
      significant anisotropic heating of the electrons. This dramatically enhances the
      collisionless tearing mode and may lead to the rapid onset of magnetic
      reconnection for current sheets near the critical scale.

PMID- 15447412
TI  - Phase-transition phenomena of 0.8 microm superfluid 3He slab.
AB  - We have investigated the transition phenomena of superfluid 3He in thin 0.8
      microm slabs with a cw-NMR method. We found that, just below the phase-transition
      temperature, only the A phase appeared at any pressure. At lower temperatures,
      the phase transition to the B phase occurred between 0.3 and 2.74 MPa. We
      obtained a universal critical thickness delta as a function of pressure. When the
      reduced slab thickness, d/xi(T), is smaller than delta, only the A phase becomes
      stable.

PMID- 15447413
TI  - Neutron-detected tomography of impurity-seeded superfluid helium.
AB  - We describe a neutron radiography technique that can be used to map the
      distribution of 3He impurities in liquid 4He, providing direct and quantitative
      access to underlying transport processes. Images reflecting finite normal- and
      superfluid-component 4He velocity fields are presented.

PMID- 15447414
TI  - Nanofilm allotrope and phase transformation of ultrathin Bi film on Si(111)-7x7.
AB  - Our scanning tunneling microscopy and electron diffraction experiments revealed
      that a new two-dimensional allotrope of Bi forms on the Si(111)-7x7 surface. This
      pseudocubic [012]-oriented allotrope is stable up to four atomic layers at room
      temperature. Above this critical thickness, the entire volume of the film starts
      to transform into a bulk single-crystal (001) phase, as the bulk contribution in
      the cohesion becomes dominant. Based on ab initio calculations, we propose that
      the new allotrope consists of black phosphorus-like puckered layers stabilized by
      saturating all the p(z) dangling bonds in the film.

PMID- 15447415
TI  - Does the interaction potential determine both the fragility of a liquid and the
      vibrational properties of its glassy state?
AB  - By performing molecular dynamics simulations of binary Lennard-Jones systems with
      three different potentials, we show that the increase of anharmonicity and
      capacity for intermolecular coupling of the potential is the cause of (i) the
      increase of kinetic fragility and nonexponentiality in the liquid state, and (ii)
      the T(g)-scaled temperature dependence of the nonergodicity parameter determined
      by the vibrations at low temperatures in the glassy state. Naturally, these
      parameters correlate with each other, as observed experimentally by T. Scopigno
      et al. [Science 302, 849 (2003)]

PMID- 15447416
TI  - Magic polyicosahedral core-shell clusters.
AB  - A new family of magic cluster structures is found by genetic global optimization,
      whose results are confirmed by density functional calculations. These clusters
      are Ag-Ni and Ag-Cu nanoparticles with an inner Ni or Cu core and an Ag external
      shell, as experimentally observed for Ag-Ni, and present a polyicosahedral
      character. The interplay of the core-shell chemical ordering with the
      polyicosahedral structural arrangement gives high-symmetry clusters of remarkable
      structural, thermodynamic, and electronic stability, which can have high melting
      points (they melt higher than pure clusters of the same size), large energy gaps,
      and (in the case of Ag-Ni) nonzero magnetic moments.

PMID- 15447417
TI  - Dynamic instabilities of fracture under biaxial strain using a phase field model.
AB  - We present a phase-field model of the propagation of fracture under plane strain.
      This model, based on simple physical considerations, is able to accurately
      reproduce the different behavior of cracks (the principle of local symmetry, the
      Griffith and Irwin criteria, and mode-I branching). In addition, we test our
      model against recent experimental findings showing the presence of oscillating
      cracks under biaxial load. Our model again reproduces well observed supercritical
      Hopf bifurcation and is therefore the first simulation which does so.

PMID- 15447418
TI  - Enhanced planar channeling of MeV protons through thin crystals.
AB  - At certain tilt alignments between a MeV proton beam and a planar channeling
      direction, a single interface lattice rotation within a crystal can result in a
      lower rate of dechanneling than at planar alignment in a perfect crystal. Such
      planar channeling enhancement arises when the beam passes through a layer
      thickness which is a half-multiple of the oscillation wavelength and then
      encounters a small interface rotation which is matched to the beam tilt angle.
      The beam is projected into the center of the phase space ellipse below the
      interface, resulting in certain trajectories undergoing a reduction in their
      transverse energy, in a manner analogous to stochastic cooling or atom laser
      cooling.

PMID- 15447419
TI  - Microscale simulation of martensitic microstructure evolution.
AB  - A new model for the evolution of multivariant martensitic microstructure in
      single crystals and polycrystals is developed. In contrast with Landau-Ginzburg
      models, which are limited in practice to nanoscale specimens, this new scale-free
      model is valid for length scales greater than 100 nm and without an upper bound.
      It is based on a thermodynamic potential in the volume fractions of the
      martensitic variants that exhibits an instability resulting in microstructure
      formation. Simulated microstructures in elastic single crystals and polycrystals
      under uniaxial loading are in qualitative agreement with those observed
      experimentally.

PMID- 15447420
TI  - Anisotropic defect-mediated melting of two-dimensional colloidal crystals.
AB  - The melting transition of anisotropic two-dimensional (2D) crystals is studied in
      a model system of superparamagnetic colloids. The anisotropy of the induced
      dipole-dipole interaction is varied by tilting the external magnetic field off
      the normal to the particle plane. By analyzing the time-dependent Lindemann
      parameter as well as translational and orientational order we observe a 2D
      smecticlike phase. The Kosterlitz-Thouless-Halperin-Nelson-Young scenario of
      isotropic melting is modified: dislocation pairs and dislocations appear with
      different probabilities depending on their orientation with respect to the in
      plane field.

PMID- 15447421
TI  - Observation of finite-size effects on a structural phase transition of 2D
      nanoislands.
AB  - We study a reversible, temperature-driven structural surface phase transition of
      Pb/Si(111) nanoislands with a variable-temperature scanning tunneling microscope.
      Our quantitative measurements indicate that the transition temperature decreases
      with decreasing island and domain size. The boundaries of the nanoislands also
      influence the transition. Careful examination of the change in the interior
      structure of nanoislands near the transition temperature allows us to image the
      effects of the thermal fluctuations.

PMID- 15447422
TI  - Coulomb sink: a novel coulomb effect on coarsening of metal nanoclusters on
      semiconductor surfaces.
AB  - We propose the concept of a "Coulomb sink" to elucidate the effect of Coulomb
      charging on coarsening of metal mesas grown on semiconductor surfaces. We show
      that a charged mesa, due to its reduced chemical potential, acts as a Coulomb
      sink and grows at the expense of neighboring neutral mesas. The theory explains
      qualitatively the most salient features of coarsening of charged Pb mesas on the
      Si(111) surface, as observed by a scanning tunneling microscope. It provides a
      potentially useful method for controlled fabrication of metal nanostructures.

PMID- 15447423
TI  - Temperature driven reversible breakdown of pseudomorphism in ultrathin Fe/Cu3Au
      films.
AB  - We observe that ultrathin Fe/Cu(3)Au(001) films in the 6-13 A thickness range,
      beyond the thickness of pseudomorphism breakdown at room temperature, exhibit a
      temperature dependent structural phase transition in the range T(c) approximately
      345-380 K. In the high temperature state the Fe film becomes pseudomorphic, while
      breakdown of pseudomorphism reversibly occurs as the system is cooled below the
      transition temperature. The difference between substrate and overlayer thermal
      expansion coefficient is highlighted as the driving force for the observed
      transition.

PMID- 15447424
TI  - General insight into CO oxidation: a density functional theory study of the
      reaction mechanism on platinum oxides.
AB  - CO oxidation on PtO2(110) has been studied using density functional theory
      calculations. Four possible reaction mechanisms were investigated and the most
      feasible one is the following: (i) the O at the bridge site of PtO2(110) reacts
      with CO on the coordinatively unsaturated site (CUS) with a negligible barrier;
      (ii) O2 adsorbs on the bridge site and then interacts with CO on the CUS to form
      an OO-CO complex; (iii) the bond of O-OCO breaks to produce CO2 with a small
      barrier (0.01 eV). The CO oxidation mechanisms on metals and metal oxides are
      rationalized by a simple model: The O-surface bonding determines the reactivity
      on surfaces; it also determines whether the atomic or molecular mechanism is
      preferred. The reactivity on metal oxides is further found to be related to the
      3rd ionization energy of the metal atom.

PMID- 15447425
TI  - Calorimetry at surfaces using high-resolution core-level photoemission.
AB  - We have developed a method to measure simultaneously the internal energy of bulk
      and the first layer atoms of a crystal. The internal energy of bulk and the
      surface atoms of lithium (110) have been evaluated from 22 K up to above the
      melting transition, applying the Debye model to the thermal broadening of the
      respective 1s photoemission lines. Our measurements clearly reveal two phase
      changes: the known liquid to solid transition and the surface melting, occurring
      50 K below the bulk melting point.

PMID- 15447426
TI  - Mechanism of gap opening in a triple-band Peierls system: in atomic wires on Si.
AB  - One dimensional (1D) metals are unstable at low temperature undergoing a metal
      insulator transition coupled with a periodic lattice distortion, a Peierls
      transition. Angle-resolved photoemission study for the 1D metallic chains of In
      on Si(111), featuring a metal-insulator transition and triple metallic bands,
      clarifies in detail how the multiple band gaps are formed at low temperature. In
      addition to the gap opening for a half-filled ideal 1D band with a proper Fermi
      surface nesting, two other quasi-1D metallic bands are found to merge into a
      single band, opening a unique but k-dependent energy gap through an interband
      charge transfer. This result introduces a novel gap-opening mechanism for a
      multiband Peierls system where the interband interaction is important.

PMID- 15447427
TI  - Direct evidence of the charge ordered phase transition of indium nanowires on
      Si111.
AB  - A controversial issue of the driving force for the phase transition of the one
      dimensional (1D) metallic In wires on Si(111) is studied by low-temperature
      scanning tunneling microscopy and spectroscopy. The energy gap opening and the
      longitudinal charge ordering through charge transfer at the Fermi level are
      unambiguously observed. The vacancy defects induce a local charge ordering
      decoupled from a lattice distortion above T(c), and pin the phase of charge order
      below T(c). All these results below and above T(c) including the detailed
      features such as local fluctuations strongly support the 1D charge-density-wave
      mechanism for the phase transition.

PMID- 15447428
TI  - Berry phase and de Haas-van Alphen effect in LaRhIn5.
AB  - We explain the experimental data on the magnetization of LaRhIn5 recently
      published by Goodrich et al. [Phys. Rev. Lett. 89, 026401 (2002)]]. We show that
      the magnetization of a small electron group associated with a band-contact line
      was detected in that Letter. These data provide the first observation of the
      Berry phase of electrons in metals via the de Haas-van Alphen effect.

PMID- 15447429
TI  - Sliding-induced decoupling and charge transfer between the coexisting Q1 and Q2
      charge density waves in NbSe3.
AB  - Using high-resolution x-ray scattering in the presence of an applied current, we
      report evidence for a dynamical decoupling between the two NbSe3 charge-density
      waves (CDWs), Q1 (T(C1)=145 K) and Q2 (T(C2)=59 K), coexisting below T(C2).
      Simultaneous and oppositely directed shifts of the relevant CDW superlattice
      spots develop above a threshold current which we identify as the depinning
      threshold I(C1) for the more strongly pinned upper CDW Q1 (I(C1) approximately
      10I(C2)). In contrast with shifts induced by current conversion processes, the
      present effect is not current polarized and is not limited to the current-contact
      regions. We propose a model which explains this instability through a sliding
      induced charge transfer between the two electronic reservoirs corresponding to
      the Q1 and Q2 CDWs.

PMID- 15447431
TI  - Quasiparticle anisotropy and pseudogap formation from the weak-coupling
      renormalization group point of view.
AB  - Using the one-loop functional renormalization group technique, we evaluate the
      self-energy in the weak-coupling regime of the 2D t-t(') Hubbard model. At van
      Hove (vH) band fillings and at low temperatures, the quasiparticle weight along
      the Fermi surface (FS) continuously vanishes on approaching the (pi,0) point
      where the quasiparticle concept is invalid. Away from vH band fillings the
      quasiparticle peak is formed inside an anisotropic pseudogap and the self-energy
      has the conventional Fermi-liquid characteristics near the Fermi level. The
      spectral weight of the quasiparticle features is reduced on parts of the FS
      between the near vicinity of hot spots and the FS points closest to (pi,0) and
      (0,pi).

PMID- 15447430
TI  - Direct observation of self-trapped vibrational states in alpha-helices.
AB  - Femtosecond infrared pump-probe spectroscopy of the N-H mode of a stable alpha
      helix reveals two excited-state absorption bands, which disappear upon unfolding
      of the helix. A quantitative comparison with polaron theory shows that these two
      bands reflect two types of two-vibron bound states connected to the trapping of
      two vibrons at the same site and at nearest neighbor sites, respectively. The
      latter states originate from an acoustic phonon in the helix, which correlates
      adjacent sites.

PMID- 15447432
TI  - Spin mass of an electron liquid.
AB  - We show that in order to calculate correctly the spin current carried by a
      quasiparticle in an electron liquid one must use an effective "spin mass" m(s)
      that is larger than both the band mass m(b), which determines the charge current,
      and the quasiparticle effective mass m(*), which determines the heat capacity. We
      present two independent estimates of the spin mass enhancement, m(s)/m(b), in two
      and three-dimensional electron liquids, based on (i) previously calculated
      values of the Landau parameters and (ii) a recent theory of the dynamical local
      field factor in the spin channel. Both methods yield a significant spin mass
      enhancement, which is larger in two dimensions than in three.

PMID- 15447433
TI  - Interfacial resonance state probed by spin-polarized tunneling in epitaxial
      Fe/MgO/Fe tunnel junctions.
AB  - The direct impact of the electronic structure on spin-polarized transport has
      been experimentally proven in high-quality Fe/MgO/Fe epitaxial magnetic tunnel
      junctions, with an extremely flat bottom Fe/MgO interface. The voltage variation
      of the conductance points out the signature of an interfacial resonance state
      located in the minority band of Fe(001). When coupled to a metallic bulk state,
      this spin-polarized interfacial state enhances the band matching at the interface
      and therefore increases strongly the conductivity in the antiparallel
      magnetization configuration. Consequently, the tunnel magnetoresistance is found
      to be positive below 0.2 V and negative above. On the other hand, when the
      interfacial state is either destroyed by roughness-related disorder or not
      coupled to the bulk, the magnetoresistance is almost independent on the bias
      voltage.

PMID- 15447434
TI  - Josephson junctions as threshold detectors for full counting statistics.
AB  - We discuss how threshold detectors can be used for a direct measurement of the
      full distribution of current fluctuations and how to exploit Josephson junctions
      in this respect. We propose a scheme to characterize the full counting statistics
      from the current dependence of the escape rate measured. We illustrate the scheme
      with explicit results for tunnel, diffusive, and quasiballistic mesoscopic
      conductors.

PMID- 15447435
TI  - Magnetic-field asymmetry of nonlinear mesoscopic transport.
AB  - We investigate departures of the Onsager relations in the nonlinear regime of
      electronic transport through mesoscopic systems. We show that the nonlinear
      current-voltage characteristic is not an even function of the magnetic field due
      only to the magnetic-field dependence of the screening potential within the
      conductor. We illustrate this result for two types of conductors: A quantum Hall
      bar with an antidot and a chaotic cavity connected to quantum point contacts. For
      the chaotic cavity we obtain through random matrix theory an asymmetry in the
      fluctuations of the nonlinear conductance that vanishes rapidly with the size of
      the contacts.

PMID- 15447436
TI  - Coulomb-modified Fano resonance in a one-lead quantum dot.
AB  - We investigate a tunable Fano interferometer consisting of a quantum dot coupled
      via tunneling to a one-dimensional channel. In addition to Fano resonance, the
      channel shows strong Coulomb response to the dot, with a single electron
      modulating channel conductance by factors up to 100. Where these effects coexist,
      line shapes with up to four extrema are found. A model of Coulomb-modified Fano
      resonance is developed and gives excellent agreement with experiment.

PMID- 15447437
TI  - Measurement efficiency and n-shot readout of spin qubits.
AB  - We consider electron spin qubits in quantum dots and define a measurement
      efficiency e to characterize reliable measurements via n-shot readouts. We
      propose various implementations based on a double dot and a quantum point contact
      (QPC) and show that the associated efficiencies e vary between 50% and 100%,
      allowing single-shot readout in the latter case. We model the readout
      microscopically and derive its time dynamics in terms of a generalized master
      equation, calculate the QPC current, and show that it allows spin readout under
      realistic conditions.

PMID- 15447438
TI  - Metal-to-insulator crossover in YBa2Cu3Oy probed by low-temperature quasiparticle
      heat transport.
AB  - It was recently demonstrated that in La2-xSrxCuO4 the magnetic-field (H)
      dependence of the low-temperature thermal conductivity kappa up to 16 T reflects
      whether the normal state under high magnetic field is a metal or an insulator. We
      measure the H dependence of kappa in YBa(2)Cu(3)O(y) (YBCO) at subkelvin
      temperatures for a wide doping range, and find that at low doping the kappa(H)
      behavior signifies the change in the ground state in this system as well.
      Surprisingly, the critical doping is found to be located deeply inside the
      underdoped region, about the hole doping of 0.07 hole/Cu; this critical doping is
      apparently related to the stripe correlations as revealed by the in-plane
      resistivity anisotropy.

PMID- 15447439
TI  - Microwave-induced thermal escape in Josephson junctions.
AB  - We investigate, by experiments and numerical simulations, thermal activation
      processes of Josephson tunnel junctions in the presence of microwave radiation.
      When the applied signal resonates with the Josephson plasma frequency
      oscillations, the switching current may become multivalued in a temperature range
      far exceeding the classical to quantum crossover temperature. Plots of the
      switching currents traced as a function of the applied signal frequency show very
      good agreement with the functional forms expected from Josephson plasma frequency
      dependencies on the bias current. Throughout, numerical simulations of the
      corresponding thermally driven classical Josephson junction model show very good
      agreement with the experimental data.

PMID- 15447440
TI  - Survival of the d-wave superconducting state near the edge of antiferromagnetism
      in the cuprate phase diagram.
AB  - In the cuprate superconductor YBa2Cu3O6+x, hole doping in the CuO2 layers is
      controlled by both oxygen content and the degree of oxygen ordering. At the
      composition YBa2Cu3O6.35, the ordering can occur at room temperature, thereby
      tuning the hole doping so that the superconducting critical temperature gradually
      rises from 0 to 20 K. Here we exploit this to study the c-axis penetration depth
      as a function of temperature and doping. The temperature dependence shows the d
      wave superconductor surviving to very low doping, with no sign of another ordered
      phase interfering with the nodal quasiparticles. The only apparent doping
      dependence is a smooth decline of superfluid density as T(c) decreases.

PMID- 15447441
TI  - Broken particle-hole symmetry at atomically flat a-axis YBa2Cu3O7-delta
      interfaces.
AB  - We have studied quasiparticle tunneling into atomically flat a-axis films of
      YBa(2)Cu(3)O(7-delta) and DyBa(2)Cu(3)O(7-delta) through epitaxial CaTiO3
      barriers. The junction heterostructures were grown by oxide molecular beam
      epitaxy and were carefully optimized using in situ monitoring techniques,
      resulting in unprecedented crystalline perfection of the superconductor-insulator
      interface. Below T(c), the tunneling conductance shows the evolution of a large
      unexpected asymmetrical feature near zero-bias. This is evidence that
      superconducting YBCO crystals, atomically truncated along the lobe direction with
      a titanate layer, have intrinsically broken particle-hole symmetry over
      macroscopically large areas.

PMID- 15447442
TI  - Direct imaging of temperature-dependent layered antiferromagnetism of a magnetic
      oxide.
AB  - With the use of a newly developed spin-polarized scanning electron microscope, we
      have succeeded in obtaining the real-space images of the layered
      antiferromagnetic state concurrent with 1-nm-stepped atomic terraces in layered
      structure manganite La1.4Sr1.6Mn2O7. The three-dimensional analysis of spin
      alignment could further reveal the temperature-dependent spin reorientation and
      the anfiferromagnetic domain walls on the atomic terraces. These ensure the use
      of the present microscopy for quantitative analysis of local magnetic structures
      in a broader range of materials, including magnetic oxides and nanomaterials.

PMID- 15447443
TI  - Field-induced ferromagnetic metallic state in the bilayer manganite
      (La0.4Pr0.6)1.2Sr1.8Mn2O7, probed by neutron scattering.
AB  - The bilayer manganite La1.2Sr1.8Mn2O7 exhibits a phase transition from a
      paramagnetic insulating (PI) to a ferromagnetic metallic (FM) state with a
      colossal magnetoresistance (CMR) effect. Upon 60% Pr substitution, magnetic order
      and PI to FM transition are suppressed. Application of a moderate magnetic field
      restores an FM state with a CMR effect. Neutron scattering by a single crystal of
      (La0.4Pr0.6)1.2Sr1.8Mn2O7, under a magnetic field of 5 T, has revealed a long
      range and homogeneous ferromagnetic order. In the PI phase, under zero field,
      correlated lattice polarons have been detected. At 28 K, under 5 T, the spin wave
      dispersion curve determines an in-plane isotropic spin wave stiffness constant of
      146 meV A(2). So the magnetic field not only generates a homogeneous
      ferromagnetic ground state, but also restores a magnetic coupling characteristic
      of FM CMR manganites.

PMID- 15447444
TI  - Magnon squeezing in an antiferromagnet: reducing the spin noise below the
      standard quantum limit.
AB  - We report the first experimental demonstration of quantum squeezing of a
      collective spin-wave excitation (magnon) using femtosecond optical pulses to
      generate correlations involving pairs of spins in an antiferromagnetic insulator
      MnF2. In the squeezed state, the fluctuations of the magnetization of a
      crystallographic unit cell vary periodically in time and are reduced below that
      of the ground-state quantum noise.

PMID- 15447445
TI  - Theory of inelastic scattering from magnetic impurities.
AB  - We use the numerical renormalization group method to calculate the single
      particle matrix elements T of the many-body T matrix of the conduction electrons
      scattered by a magnetic impurity at T=0 temperature. Since T determines both the
      total and the elastic, spin-diagonal scattering cross sections, we are able to
      compute the full energy, spin, and magnetic field dependence of the inelastic
      scattering cross section sigma(inel)(omega). We find an almost linear frequency
      dependence of sigma(inel)(omega) below the Kondo temperature T(K), which crosses
      over to a omega(2) behavior only at extremely low energies. Our method can be
      generalized to other quantum impurity models.

PMID- 15447446
TI  - Conditions for noncollinear instabilities of ferromagnetic materials.
AB  - Two criteria have been identified here which determine whether a magnetic metal
      orders in a collinear (e.g., ferromagnet) or noncollinear (e.g., spin-spiral)
      arrangement. These criteria involve the ratio between the strength of the
      exchange interaction and the width of the electron bands, as well as Fermi
      surface nesting between spin-up and spin-down sheets of the Fermi surface. Based
      on our analysis we predict that even typical ferromagnetic materials (e.g., Fe,
      Co, and Ni) should be possible to stabilize in a noncollinear magnetic order in,
      e.g., high pressure experiments.

PMID- 15447447
TI  - Magnetic-field induced spin-Peierls instability in strongly frustrated quantum
      spin lattices.
AB  - For a class of frustrated antiferromagnetic spin lattices (in particular, the
      square-kagome and kagome lattices) we discuss the impact of recently discovered
      exact eigenstates on the stability of the lattice against distortions. These
      eigenstates consist of independent localized magnons embedded in a ferromagnetic
      environment and become ground states in high magnetic fields. For appropriate
      lattice distortions fitting to the structure of the localized magnons the
      lowering of magnetic energy can be calculated exactly and is proportional to the
      displacement of atoms leading to a spin-Peierls lattice instability. Since these
      localized states are present only for high magnetic fields, this instability
      might be driven by magnetic-field. The hysteresis of the spin-Peierls transition
      is also discussed.

PMID- 15447448
TI  - Colossal magnetodielectric effects in DyMn2O5.
AB  - We have investigated the detailed magnetic field dependence of the electric
      polarization and dielectric constant in (Tb,Dy,Ho)Mn2O5 where magnetic and
      ferroelectric transitions are intimately coupled. Our fundamental discovery is
      the unprecedented large change of the dielectric constant with magnetic field,
      particularly in DyMn2O5, associated with an unusual commensurate-incommensurate
      magnetic transition. This extraordinary effect appears to originate from the high
      sensitivity of the incommensurate state to external perturbation.

PMID- 15447449
TI  - Photocurrents in nanotube junctions.
AB  - Photocurrents in nanotube p-n junctions are calculated using a nonequilibrium
      Green function quantum transport formalism. The short-circuit photocurrent
      displays band-to-band transitions and photon-assisted tunneling, and has multiple
      sharp peaks in the infrared, visible, and ultraviolet. The operation of such
      devices in the nanoscale regime leads to unusual size effects, where the
      photocurrent scales linearly and oscillates with device length. The oscillations
      can be related to the density of states in the valence band, a factor that also
      determines the relative magnitude of the photoresponse for different bands.

PMID- 15447450
TI  - Effective medium theory of left-handed materials.
AB  - We analyze the transmission and reflection data obtained through transfer matrix
      calculations on metamaterials of finite lengths, to determine their effective
      permittivity epsilon and permeability micro. Our study concerns metamaterial
      structures composed of periodic arrangements of wires, cut wires, split ring
      resonators (SRRs), closed SRRs, and both wires and SRRs. We find that the SRRs
      have a strong electric response, equivalent to that of cut wires, which dominates
      the behavior of left-handed materials (LHM). Analytical expressions for the
      effective parameters of the different structures are given, which can be used to
      explain the transmission characteristics of LHMs. Of particular relevance is the
      criterion introduced by our studies to identify if an experimental transmission
      peak is left or right handed.

PMID- 15447451
TI  - Measurement of the radiative and nonradiative decay rates of single CdSe
      nanocrystals through a controlled modification of their spontaneous emission.
AB  - We present a simple method to measure the radiative and nonradiative
      recombination rates of individual fluorescent emitters at room temperature. By
      placing a single molecule successively close and far from a dielectric interface
      and simultaneously measuring its photoluminescence decay and its orientation,
      both the radiative and nonradiative recombination rates can be determined. For
      CdSe nanocrystals, our results demonstrate that the fluorescence quantum
      efficiency, determined at the single-molecule level, is 98% in average, far above
      the value expected from conventional ensemble experiments. The bidimensional
      nature of the transition dipole is also directly evidenced from a single-particle
      measurement.

PMID- 15447452
TI  - Excited states mapped by secondary photoemission.
AB  - We report on angle-resolved photoemission (ARPES) experiments on Cu(110) using Mg
      K(alpha) radiation. The secondary emission (SE) fine structure of electrons below
      50 eV is found to map the empty band structure relevant for absolute band mapping
      in ARPES. The finding is based on a direct comparison of our experiments with
      very low-energy electron diffraction data [Phys. Rev. Lett. 81, 4943 (1998)]]
      recently shown to map the unoccupied states representing the photoemission final
      state. This suggests a new theoretical approach to the SE process treating the
      outgoing electron state as the time-reversed diffraction state.

PMID- 15447453
TI  - Low frequency rhythms in human DNA sequences: a key to the organization of gene
      location and orientation?
AB  - We explore large-scale nucleotide compositional fluctuations of the human genome
      using multiresolution techniques. Analysis of the GC content and of the AT and GC
      skews reveals the existence of rhythms with two main periods of 110+/-20 kb and
      400+/-50 kb that enlighten a remarkable cooperative gene organization. We show
      that the observed nonlinear oscillations are likely to display all the
      characteristic features of chaotic strange attractors which suggests a very
      attractive deterministic picture: gene orientation and location, in relation with
      the structure and dynamics of chromatin, might be governed by a low-dimensional
      nonlinear dynamical system.

PMID- 15447454
TI  - Periodic adhesive fingers between contacting cells.
AB  - We study in detail the properties of fingers, a particular type of cell-cell
      adhesive structures appearing in adherens junctions. These periodic patterns
      break the symmetry of cell-cell contacts. We show that finger formation is driven
      by cadherin interactions and actin growth. A theoretical model is introduced in
      which the growth of fingers is limited by membrane tension. The steady shape and
      formation kinetics of fingers are experimentally measured and compared with the
      theoretical predictions.

PMID- 15447455
TI  - Dynamics of nonequilibrium membrane bud formation.
AB  - The dynamical response of a lipid membrane to a local perturbation of its
      molecular symmetry is investigated theoretically. A density asymmetry between the
      two membrane leaflets is predominantly released by in-plane lipid diffusion or
      membrane curvature, depending upon the spatial extent of the perturbation. It may
      result in the formation of nonequilibrium structures (buds), for which a
      dynamical size selection is observed. A preferred size in the microm range is
      predicted, as a signature of the crossover between membrane and solvent dominated
      dynamical membrane response.

PMID- 15447456
TI  - Novel formulation of nonlocal electrostatics.
AB  - The accurate modeling of the dielectric properties of water is crucial for many
      applications in physics, computational chemistry, and molecular biology. This
      becomes possible in the framework of nonlocal electrostatics, for which we
      propose a novel formulation allowing for numerical solutions for the nontrivial
      molecular geometries arising in the applications mentioned before. Our approach
      is based on the introduction of a secondary field psi, which acts as the
      potential for the rotation free part of the dielectric displacement field D. For
      many relevant models, the dielectric function of the medium can be expressed as
      the Green's function of a local differential operator. In this case, the
      resulting coupled Poisson (-Boltzmann) equations for psi and the electrostatic
      potential phi reduce to a system of coupled partial differential equations. The
      approach is illustrated by its application to simple geometries.

PMID- 15447457
TI  - Dynamic phase transitions in cell spreading.
AB  - We monitored isotropic spreading of mouse embryonic fibroblasts on fibronectin
      coated substrates. Cell adhesion area versus time was measured via total internal
      reflection fluorescence microscopy. Spreading proceeds in well-defined phases. We
      found a power-law area growth with distinct exponents in three sequential phases,
      which we denote as basal, continuous, and contractile spreading. High resolution
      differential interference contrast microscopy was used to characterize local
      membrane dynamics at the spreading front. Fourier power spectra of membrane
      velocity reveal the sudden development of periodic membrane retractions at the
      transition from continuous to contractile spreading. We propose that the
      classification of cell spreading into phases with distinct functional
      characteristics and protein activity serves as a paradigm for a general program
      of a phase classification of cellular phenotype.

PMID- 15447458
TI  - Eikonal formulation of the minimal principle for scroll wave filaments.
AB  - Recently, Wellner et al. [Proc. Natl. Acad. Sci. U.S.A. 99, 8015 (2002)]]
      proposed a principle for predicting a stable scroll wave filament shape as a
      geodesic in a 3D space with a metric determined by the inverse diffusivity tensor
      of the medium. Using the Hamilton-Jacobi theory we show that this geodesic is the
      shortest path for a wave propagating through the medium. This allows the use of
      shortest path algorithms to predict filament shapes, which we confirm numerically
      for a medium with orthotropic anisotropy. Our method can be used in cardiac
      tissue experiments since it does not require knowledge of the tissue anisotropy.

PMID- 15447459
TI  - Collective dynamics of lipid membranes studied by inelastic neutron scattering.
AB  - We have studied the collective short wavelength dynamics in deuterated 1,2
      dimyristoyl-sn-glycero-3-phoshatidylcholine (DMPC) bilayers by inelastic neutron
      scattering. The corresponding dispersion relation variant Planck's over 2pi
      omega(Q) is presented for the gel and the fluid phase of this model system. The
      temperature dependence of the inelastic excitations indicates a phase coexistence
      between the two phases over a broad range and leads to a different assignment of
      excitations from that reported in a preceding inelastic x-ray scattering study
      [Phys. Rev. Lett. 86, 740 (2001)]]. As a consequence, we find that the minimum in
      the dispersion relation is actually deeper in the gel than in the fluid phase.
      Finally, we can clearly identify an additional nondispersive (optical) mode
      predicted by molecular dynamics simulations [Phys. Rev. Lett. 87, 238101
      (2001)]].

PMID- 15447460
TI  - Localized single-stranded bubble mechanism for cyclization of short double helix
      DNA.
AB  - Recent experiments indicate that double-stranded DNA molecules of approximately
      100 base pairs in length have a probability of cyclization which is up to 10(5)
      times larger than that expected based on the known bending modulus of the double
      helix. We argue that for short molecules, the formation of a few base pairs of
      single-stranded DNA can provide a "flexible hinge" that facilitates loop
      formation. A detailed calculation shows that this mechanism explains the
      experimental data.

PMID- 15447461
TI  - Stresses in isostatic granular systems and emergence of force chains.
AB  - Progress is reported on several questions that bedevil understanding of granular
      systems: (i) Are the stress equations elliptic, parabolic, or hyperbolic? (ii)
      How can the often-observed force chains be predicted from a first-principles
      continuous theory? (iii) How do we relate insight from isostatic systems to
      general packings? Explicit equations are derived for the stress components in two
      dimensions including the dependence on the local structure. The equations are
      shown to be hyperbolic and their general solutions, as well as the Green
      function, are found. It is shown that the solutions give rise to force chains,
      and the explicit dependence of the force chains trajectories and magnitudes on
      the local geometry is predicted. Direct experimental tests of the predictions are
      proposed. Finally, a framework is proposed to relate the analysis to nonisostatic
      and more realistic granular assemblies.

PMID- 15447462
TI  - Limits to gelation in colloidal aggregation.
AB  - We show that the dynamics of large fractal colloid aggregates are well described
      by a combination of translational and rotational diffusion and internal elastic
      fluctuations, allowing both the aggregate size and internal elasticity to be
      determined by dynamic light scattering. The comparison of results obtained in
      microgravity and on Earth demonstrates that cluster growth is limited by gravity
      induced restructuring. In the absence of gravity, thermal fluctuations ultimately
      inhibit fractal growth and set the fundamental limitation to the lowest volume
      fraction which will gel.

PMID- 15447463
TI  - Capillary freezing or complete wetting of hard spheres in a planar hard slit?
AB  - Extensive simulations of a hard sphere fluid confined between two planar hard
      walls show the onset of crystalline layers at the walls at about 98.3% of bulk
      crystallization density rho(f) independent of the wall separations L(z), and is,
      hence, a single wall phenomenon. As the bulk density far from the wall rho(b)
      increases, the thickness of the crystalline film appears to increase
      logarithmically, with (rho(f)-rho(b)) indicating complete wetting by the hard
      sphere crystal of the wall-fluid interface. Increasing rho(b) further, we observe
      a jump in the adsorption which depends on L(z) and corresponds to capillary
      freezing. The formation of crystalline layers below bulk crystallization, the
      logarithmic growth of the crystalline film, its independence of L(z), and its
      clear distinction from capillary freezing lend strong evidence for complete
      wetting by the hard sphere crystal at the wall-fluid interface.

PMID- 15447464
TI  - Dynamic roughening and fluctuations of dipolar chains.
AB  - Nonmagnetic particles in a carrier ferrofluid acquire an effective dipolar moment
      when placed in an external magnetic field. This fact leads them to form chains
      that will roughen due to Brownian motion when the magnetic field is decreased. We
      study this process through experiments, theory and simulations, three methods
      that agree on the scaling behavior over 5 orders of magnitude. The rms width goes
      initially as t(1/2), then as t(1/4) before it saturates. We show how these
      results complement existing results on polymer chains, and how the chain dynamics
      may be described by a recent non-Markovian formulation of anomalous diffusion.

PMID- 15447465
TI  - BLOCH-front turbulence in a periodically forced Belousov-Zhabotinsky reaction.
AB  - Experiments on a periodically forced Belousov-Zhabotinsky chemical reaction show
      front breakup into a state of spatiotemporal disorder involving continual events
      of spiral-vortex nucleation and destruction. Using the amplitude equation for
      forced oscillatory systems and the normal form equations for a curved front line,
      we identify the mechanism of front breakup and explain the experimental
      observations.

PMID- 15447466
TI  - Comment on "self-organized periodic photonic structure in a nonchiral liquid
      crystal".

PMID- 15447467
TI  - Coherent phonons: electronic softening or anharmonicity?

PMID- 15447469
TI  - Stochastic nonlinear differential equation generating 1/f noise.
AB  - Starting from the simple point process model of 1/f noise, we derive a stochastic
      nonlinear differential equation for the signal exhibiting 1/f noise, in any
      desirably wide range of frequency. A stochastic differential equation (the
      general Langevin equation with a multiplicative noise) that gives 1/f noise is
      derived. The solution of the equation exhibits the power-law distribution. The
      process with 1/f noise is demonstrated by the numerical solution of the derived
      equation with the appropriate restriction of the diffusion of the signal in some
      finite interval.

PMID- 15447470
TI  - Grain boundary dynamics under mechanical annealing in two-dimensional colloids.
AB  - Two-dimensional (2D) colloids embedded in a soap film are employed to study the
      structures and dynamics of grain boundaries (GBs). While a soap film is drawn
      vertically from a concentrated bulk suspension, the colloidal particles self
      assemble to form polycrystalline structures with a typical grain size of about
      100 lattice spaces. Studies of these grain boundaries reveal that the GB lines
      are faceted at "atomic" scale, leading to a constant energy per unit length along
      each line. The measured GB energy as a function of misfit angle is in agreement
      with Reed-Shockley's theoretical predictions. When an external mechanical
      vibration is applied to the bulk suspension, the grain boundaries are observed to
      migrate and grains to rotate under the stress field induced by the vibration. The
      total length of the grain boundaries is found to diminish logarithmically with
      time, with the rate constant being a function of the excitation strength. This
      phenomenon, called "mechanical annealing," provides a robust means to grow large
      2D single-domain crystals.

PMID- 15447471
TI  - Molecular discreteness in reaction-diffusion systems yields steady states not
      seen in the continuum limit.
AB  - We investigate the effects of the spatial discreteness of molecules in reaction
      diffusion systems. It is found that discreteness within the so-called Kuramoto
      length can lead to a localization of molecules, resulting in novel steady states
      that do not exist in the continuous case. These states are analyzed theoretically
      as the fixed points of accelerated localized reactions, an approach that was
      verified to be in good agreement with stochastic particle simulations. The
      relevance of this discreteness-induced state to biological intracellular
      processes is discussed.

PMID- 15447472
TI  - Effects of stacking on the configurations and elasticity of single-stranded
      nucleic acids.
AB  - Stacking interactions in single-stranded nucleic acids give rise to
      configurations of an annealed rod-coil multiblock copolymer. Theoretical analysis
      identifies the following resulting signatures for long homopolynucleotides: a
      nonmonotonic dependence of size on temperature, the corresponding effects on
      cyclization and a plateau in the extension force law. Explicit numerical results
      for polydeoxyadenylate [poly(dA)] and polyriboadenylate [poly(rU)] are presented.

PMID- 15447473
TI  - Reentrant behavior of the spinodal curve in a nonequilibrium ferromagnet.
AB  - The metastable behavior of a kinetic Ising-type ferromagnetic model system in
      which a generic type of microscopic disorder induces nonequilibrium steady states
      is studied by computer simulation and a mean-field approach. We pay attention, in
      particular, to the spinodal curve or intrinsic coercive field that separates the
      metastable region from the unstable one. We find that, under strong
      nonequilibrium conditions, this exhibits reentrant behavior as a function of
      temperature. That is, metastability does not happen in this regime for both low
      and high temperatures, but instead emerges for intermediate temperature, as a
      consequence of the nonlinear interplay between thermal and nonequilibrium
      fluctuations. We argue that this behavior, which is in contrast with equilibrium
      phenomenology and could occur in actual impure specimens, might be related to the
      presence of an effective multiplicative noise in the system.

PMID- 15447474
TI  - Brownian rectifiers in the presence of temporally asymmetric unbiased forces.
AB  - The efficiency of energy transduction in a temporally asymmetric rocked ratchet
      is studied. Time asymmetry favors current in one direction and suppresses it in
      the opposite direction due to which large efficiency approximately 50% is readily
      obtained. The spatial asymmetry in the potential together with system
      inhomogeneity may help in further enhancing the efficiency. Fine tuning of system
      parameters considered leads to multiple current reversals even in the adiabatic
      regime.

PMID- 15447475
TI  - Effects of noise near a homoclinic bifurcation in an electrochemical system.
AB  - The interaction of external noise with an electrochemical oscillator (anodic
      dissolution of iron) has been studied experimentally on both sides of the
      homoclinic bifurcation. In the oscillatory regime the regularity of the limit
      cycle behavior was destroyed with increasing noise amplitude until no periodicity
      was observable any more. In contrast, the response of the excitable state (fixed
      point regime) became more regular at intermediate noise levels.

PMID- 15447476
TI  - Constructive approximations to the q=1/2 maximum entropy distribution from
      redundant and noisy data.
AB  - The problem of constructing the q=1/2 nonextensive maximum entropy distributions
      from redundant and noisy data is considered. A strategy is proposed, which
      evolves through the following steps. (i) Independent constraints are first
      preselected by recourse to a data-independent technique to be discussed here.
      (ii) The data are a posteriori used to determine the parameters of the
      distribution by a previously introduced forward approach. (iii) A backward
      approach is proposed for reducing the parameters of such distribution. The
      previously introduced forward approach is generalized here in order to make it
      suitable for dealing with very noisy data.

PMID- 15447477
TI  - Kinetic models of ion transport through a nanopore.
AB  - Kinetic equations for the stationary state distribution function of ions moving
      through narrow pores are solved for a number of 1D models of single ion
      transport. Ions move through pores of length L, under the action of a constant
      external field and of a concentration gradient. The interaction of single ions
      with the confining pore surface and with water molecules inside the pore are
      modeled by a Fokker-Planck term in the kinetic equation, or by uncorrelated
      collisions with thermalizing centers distributed along the pore. The temporary
      binding of ions to polar residues lining the pore is modeled by stopping traps or
      energy barriers. Analytic expressions for the stationary ion current through the
      pore are derived for several versions of the model, as functions of key physical
      parameters. In all cases, saturation of the current at high fields is predicted.
      Such simple models, for which results are analytic, may prove useful in the study
      of the current/voltage relations of ion channels through membranes.

PMID- 15447478
TI  - Signal estimation and threshold optimization using an array of bithreshold
      elements.
AB  - We consider the problem of optimizing signal transmission through multichannel
      noisy devices. We investigate an array of bithreshold noisy devices which is
      connected in parallel and convergent on a summing center. Utilizing the concept
      of noise-induced linearization we derive an analytical approximation of the
      normalized power norm and clarify the relation between the optimum threshold and
      the standard deviation of noises. We show that the optimum threshold value is
      0.63 times the standard deviation of the noises. This relation is applicable to
      both subthreshold and suprathreshold inputs.

PMID- 15447479
TI  - Thermoacoustic boundary layers near the liquid-vapor critical point.
AB  - We measure and calculate the sound attenuation within thermoacoustic boundary
      layers between solid surfaces and xenon at its critical density rhoc as the
      reduced temperature tau identical with (T- Tc)/Tc approaches zero. (Tc is the
      critical temperature.) Using the known thermophysical properties of xenon, we
      predict that the attenuation at the boundary first increases approximately as
      tau(-0.6) and then saturates when the effusivity of the xenon exceeds that of the
      solid. [The effusivity is epsilon identical with (rhoCPlambdaT)(1/2), where CP is
      the isobaric specific heat and lambdaT is the thermal conductivity.] The model
      correctly predicts (+/-1.0%) the quality factors Q of resonances measured in a
      stainless steel resonator (epsilon(ss) =6400 kg K(-1) s(-5/2)); it also predicts
      the observed increase of the Q, by up to a factor of 8, when the resonator is
      coated with a polymer (epsilon(pr) =370 kg K(-1) s(-5/2)). The test data span the
      frequency range 0.1<f<7.5 kHz and the reduced temperature range 10(-3) <tau< 10(
      1). We also predict that the thickness deltaT of the thermal boundary layer in
      the xenon decreases approximately as tau(0.4) until 2pifgammazeta/(rhoc2)
      approximately 0.5. (zeta is the bulk viscosity, gamma is the heat capacity ratio,
      and c is the speed of sound.) Still closer to Tc, deltaT becomes complex and its
      magnitude increases. These predictions concerning deltaT have not yet been
      tested. We deduce accurate values for the heat capacity CV and thermal
      conductivity lambdaT for xenon in the range 10(-3) <tau< 10(-1).

PMID- 15447480
TI  - Stripe patterns in two-dimensional systems with core-corona molecular
      architecture.
AB  - The behavior of a two-dimensional system of particles interacting through a
      potential consisting of a hard core surrounded by a soft repulsive corona is
      investigated at several densities and temperatures. We find that the competition
      between hard and soft repulsions gives origin to the spontaneous formation of
      spatial patterns resembling stripe textures. The effect of varying the hard and
      soft core radii ratio as well as that of adding an attractive component to the
      interparticle interaction is studied. The model investigated is relevant for
      macromolecular topologies possessing two intrinsic length scales.

PMID- 15447481
TI  - Determination of effective pair interactions from the structure factor.
AB  - In this work we present an efficient procedure to evaluate effective pair
      potentials, compatible with "experimental" structure factors, using a Monte Carlo
      simulation scheme. The procedure does not require the use of inverse Fourier
      transforms and is robust and rapidly convergent. As a test case the structure
      factor of liquid Selenium obtained from a Tight-Binding Molecular Dynamics
      simulation is inverted to obtain an effective pair potential and, as a by
      product, the pair distribution function. The inversion procedure yields a pair
      structure in perfect agreement with the original molecular dynamics calculations
      and the analysis of the triplet structure and the dynamics also illustrates the
      limitations of the use of pair potentials in the description of liquids with
      strongly directional bonding, such as the covalent liquid Selenium.

PMID- 15447482
TI  - Mode-coupling theory and molecular dynamics simulation for heat conduction in a
      chain with transverse motions.
AB  - We study heat conduction in a 1D chain of particles with longitudinal as well as
      transverse motions. The particles are connected by 2D harmonic springs together
      with bending angle interactions. The problem is analyzed by mode-coupling theory
      and compared with molecular dynamics. We find very good, quantitative agreement
      for the damping of modes between a full mode-coupling theory and molecular
      dynamics result, and a simplified mode-coupling theory gives qualitative
      description of the damping. The theories predict generically that thermal
      conductance diverges as N(1/3) as the size N increases for systems terminated
      with heat baths at the ends. The N(2/5) dependence is also observed in molecular
      dynamics, which we attribute to crossover effect.

PMID- 15447483
TI  - Thermophoretic force and velocity of nanoparticles in the free molecule regime.
AB  - We extend our previous gas-kinetic theory analysis of drag force in a uniform
      temperature field [Li and Wang, Phys. Rev. E. 68, 061206 (2003); 68, 061207
      (2003)] to particle transport in fluids with nonuniform temperature. Formulations
      for drag and thermophoretic forces are proposed for nanoparticle transport in low
      density gases. We specifically consider the influence of nonrigid body collision
      due to van der Waals or other forces between the particle and gas molecules and
      find that these forces play a notable role for particles a few nanometers in
      size. It is shown that the present formulations can be easily reduced to the
      classical result of Waldmann [Z. Naturforsch. A 14a, 589 (1959)] by assuming
      rigid body collision. From the force formulations we also obtain the equation
      governing the thermophoretic velocity. This velocity is found to be highly
      sensitive to the potential energy of interactions between gas molecules and
      particle, and as such Waldmann's thermophoretic velocity is not expected to be
      accurate for nanosized particles.

PMID- 15447484
TI  - Pressure measurement in two-dimensional horizontal granular gases.
AB  - A two-dimensional granular gas is produced by vibrating vertically a partial
      layer of beads on a horizontal plate. Measurements of the force applied by the
      granular gas to the sidewalls of the container, or granular pressure, are used to
      study the effect of the shaking strength, density, bead-plate restitution
      coefficient, and particle size on the steady properties of the gas.

PMID- 15447485
TI  - Chain aggregate structure and magnetic birefringence in polydisperse ferrofluids.
AB  - The theory of particle association in chains in dilute ferrofluids and dipole
      fluids is generalized to the case of polydisperse systems. The chains could be
      formed by ferroparticles of different sizes, so various types of chain aggregates
      are considered. The probabilities of chain structure appearance are calculated,
      and the phase diagram, allowing to find the most probable structure with only the
      continuous particle size distribution known, is built. Our results demonstrate
      that in spite of a very weak dipole-dipole interaction between the small size
      fraction particles, their presence exerts a decisive influence on the ferrofluid
      microstructure. The chain shortening caused by the small particles sticking to
      the edges of chains formed by large particles is discovered theoretically. The
      latter effect is proved to exist by the recent computer simulations on bidisperse
      ferrofluid makeup. The application of the developed model to the description of
      magnetic birefringence phenomena in weak external magnetic fields shows a very
      good agreement with experimental data.

PMID- 15447486
TI  - Large structures in diblock copolymer micellar solution.
AB  - The association properties in water solution of poly(dimethylsiloxane)-b
      poly(ethyleneoxide) diblock copolymer was investigated by static and dynamic
      light scattering in a wide range of concentrations and temperatures. The presence
      of a long hydrophilic poly(ethyleneoxide) (PEO) chain causes a weak tendency to
      microphase separation of the system which is responsible for some relevant
      effects. First of all we observe a late micellization process which is
      characterized by an unusually high value of the critical micellar concentration
      (c(cmc) =0.007 g/cm3) and by an unusually small aggregation number (approximately
      6) of the generated micelles. Moreover, the composition of the highly hydrated
      micelles has been found to change sensitively with temperature. On increasing
      temperature dehydration of micelles has been observed together with a
      contemporaneous increase in the aggregation number, whereas the hydrodynamic
      radius remains constant in the whole range investigated. The long hydrophilic
      chains also stimulate an efficient entanglement process between micelles. The
      interpenetrating PEO chains belonging to different micelles causes the depletion
      of the solvent in the outer layer of micelles. The result is the formation, just
      after the micellization process takes place, of thermodynamically stable clusters
      of entangled micelles. These large structures, which are present in the system in
      small concentrations, maintain their structural properties unchanged in a wide
      range of concentrations and temperatures, and provide indirect evidence of a weak
      attractive component to the intermicellar interaction potential.

PMID- 15447487
TI  - Theory of growth by differential sedimentation, with application to snowflake
      formation.
AB  - A simple model of irreversible aggregation under differential sedimentation of
      particles in a fluid is presented. The structure of the aggregates produced by
      this process is found to feed back on the dynamics in such a way as to stabilize
      both the exponents controlling the growth rate, and the fractal dimension of the
      clusters produced at readily predictable values. The aggregation of ice crystals
      to form snowflakes is considered as a potential application of the model.

PMID- 15447488
TI  - Bending of flexible magnetic rods.
AB  - The flexible inextensible magnetic rod model is applied for the study of bending
      and buckling deformations of the paramagnetic particle chains linked by polymer
      molecules. It is shown that the existing experimental results can be reasonably
      well described by this model which takes into account the normal magnetic forces
      arising at chain bending deformation. By matching the experimentally observed
      shapes with our numerical simulation results different physical properties of the
      linked paramagnetic particle chains are determined.

PMID- 15447489
TI  - Brownian dynamics simulations of Laponite colloid suspensions.
AB  - Colloidal suspensions of Laponite clay platelets are studied by means of Brownian
      dynamics simulations. The platelets carry discrete charged sites which interact
      via a Yukawa potential. As in the paper by S. Kutter et al. [J. Chem. Phys. 112,
      311 (2000)], two models are considered. In the first one all surface sites are
      identically negative charged, whereas in the second one, rim charges of opposite
      sign are included. These models mimic the behavior of the Laponite particles in
      different media. They are employed in a series of simulations for different
      Laponite concentrations and for two values of the Debye length. For the
      equilibrium states, the system structure is studied by center-to-center and
      orientational pair distribution functions. Long-time translational and rotational
      self-diffusion coefficients are computed by two different methods, which yield
      very similar results.

PMID- 15447490
TI  - Unconventional density dependence of the stochastic dynamics in an organic
      liquid.
AB  - The density dependence of the diffusive rotational and center-of-mass dynamics of
      2-methyl-pyridine is investigated by means of the concurrent use of quasielastic
      neutron scattering and molecular dynamics simulations. The dependence of both
      translation and rotational diffusion coefficients shows a distinctive change of
      slope with increasing density taking place about rho=0.975 g/cm3. Such a change
      in the dynamics can be related to observations made in other liquids composed of
      oblate-spheroidal particles.

PMID- 15447491
TI  - Cooperativity of the beta-relaxations in aromatic polymers.
AB  - The dielectric loss spectra of a series of copolyesters of poly(ethylene
      terephthalate) and poly(ethylene isophthalate) have been measured as a function
      of temperature in a broad frequency range (10(-1)-10(9) Hz). By these
      measurements, the merging of the two relevant relaxations alpha and beta has been
      studied. The beta processes exhibit a complex temperature dependence, showing a
      clear Arrhenius dependence at temperatures well below the glass transition
      temperature, a transition zone where the characteristic relaxation time of this
      process nearly does not change with temperature, and an Arrhenius behavior with a
      higher activation energy for temperatures above the glass transition. The
      analysis of these results indicates that the beta relaxation in these systems
      presents typical characteristics of a genuine Johari-Goldstein process. This
      finding has been interpreted as due to the full monomer extension of the
      molecular motions involved in the beta relaxation in agreement with recent
      proposals.

PMID- 15447492
TI  - Microrheology of solutions of semiflexible biopolymer filaments using laser
      tweezers interferometry.
AB  - Semiflexible polymers are of great biological importance in determining the
      mechanical properties of cells. Techniques collectively known as microrheology
      have recently been developed to measure the viscoelastic properties of solutions
      of submicroliter volumes. We employ one such technique, which uses a focused
      laser beam to trap a micron-sized silica bead and interferometric photodiode
      detection to measure passively the position fluctuations of the trapped bead with
      nanometer resolution and high bandwidth. The frequency-dependent complex shear
      modulus G*(f) can be extracted from the position fluctuations via the fluctuation
      dissipation theorem and the generalized Stokes-Einstein relation. Using particle
      tracking microrheology, we report measurements of shear moduli of solutions of fd
      viruses, which are filamentous, semiflexible, and monodisperse bacteriophages,
      each 0.9 microm long, 7 nm in diameter, and having a persistence length of 2.2
      microm. Recent theoretical treatments of semiflexible polymer dynamics provide
      quantitative predictions of the rheological properties of such a model system.
      The fd samples measured span the dilute, semidilute, and concentrated regimes. In
      the dilute regime G*(f) is dominated by (rigid rod) rotational relaxation,
      whereas the high-frequency regime reflects single-semiflexible filament dynamics
      consistent with the theoretical prediction. Due to the short length of fd viruses
      used in this study, the intermediate regime does not exhibit a well-developed
      plateau. A dynamic scaling analysis gives rise to a concentration scaling of
      c(1.36) (r=0.99) in the transition regime and a frequency scaling of f(0.63)
      (r=0.98) at high frequencies.

PMID- 15447493
TI  - Phase diagram of charged dumbbells: a random phase approximation approach.
AB  - The phase diagram of the charged hard dumbbell system (hard spheres of opposite
      unit charge fixed at contact) is obtained with the use of the random phase
      approximation (RPA). The effect of the impenetrability of charged spheres on
      charge-charge fluctuations is described by introduction of a modified
      electrostatic potential. The correlations of ions in a pair are included via a
      correlation function in the RPA. The coexistence curve is in good agreement with
      Monte Carlo simulations. The relevance of the theory to the restricted primitive
      model is discussed.

PMID- 15447494
TI  - Colloidal hard-rod fluids near geometrically structured substrates.
AB  - Density functional theory is used to study colloidal hard-rod fluids near an
      individual right-angled wedge or edge as well as near a hard wall, which is
      periodically patterned with rectangular barriers. The Zwanzig model, in which the
      orientations of the rods are restricted to three orthogonal orientations but
      their positions can vary continuously, is analyzed by numerical minimization of
      the grand potential. Density and orientational order profiles, excess
      adsorptions, as well as surface and line tensions are determined. The
      calculations exhibit an enrichment [depletion] of rods lying parallel and close
      to the corner of the wedge (edge). For the fluid near the geometrically patterned
      wall, complete wetting of the wall-isotropic liquid interface by a nematic film
      occurs as a two-stage process in which first the nematic phase fills the space
      between the barriers until an almost planar isotropic-nematic liquid interface
      has formed separating the higher-density nematic fluid in the space between the
      barriers from the lower-density isotropic bulk fluid. In the second stage, a
      nematic film of diverging film thickness develops upon approaching bulk-isotropic
      nematic coexistence.

PMID- 15447495
TI  - Diffuse-charge dynamics in electrochemical systems.
AB  - The response of a model microelectrochemical system to a time-dependent applied
      voltage is analyzed. The article begins with a fresh historical review including
      electrochemistry, colloidal science, and microfluidics. The model problem
      consists of a symmetric binary electrolyte between parallel-plate blocking
      electrodes, which suddenly apply a voltage. Compact Stern layers on the
      electrodes are also taken into account. The Nernst-Planck-Poisson equations are
      first linearized and solved by Laplace transforms for small voltages, and
      numerical solutions are obtained for large voltages. The "weakly nonlinear" limit
      of thin double layers is then analyzed by matched asymptotic expansions in the
      small parameter epsilon= lambdaD/L, where lambdaD is the screening length and L
      the electrode separation. At leading order, the system initially behaves like an
      RC circuit with a response time of lambdaDL/D (not lambdaD2/D), where D is the
      ionic diffusivity, but nonlinearity violates this common picture and introduces
      multiple time scales. The charging process slows down, and neutral-salt
      adsorption by the diffuse part of the double layer couples to bulk diffusion at
      the time scale, L2/D. In the "strongly nonlinear" regime (controlled by a
      dimensionless parameter resembling the Dukhin number), this effect produces bulk
      concentration gradients, and, at very large voltages, transient space charge. The
      article concludes with an overview of more general situations involving surface
      conduction, multicomponent electrolytes, and Faradaic processes.

PMID- 15447496
TI  - Experimental investigation of the frequency dependence of the electrorheological
      effect.
AB  - The frequency dependence of the electrorheological response was studied
      experimentally in a suspension of barium titanate spherical particles suspending
      in silicone oil. In the system, only one factor, namely the frequency of the
      applied electric field, affects the electrorheological effect. The experimental
      data reflect the frequency effect more reliably and more accurately. Under the
      sinusoidal electric fields, the shear stress increases sharply with frequency
      below 500 Hz and reaches a saturated value beyond 500 Hz. The phenomena can be
      explained well with the permittivity mismatch theory. More experiments indicate
      that the electrorheological effect should be the sum of the mismatch polarization
      and the interfacial polarization.

PMID- 15447497
TI  - Spinodal dewetting in a volatile liquid film.
AB  - The coexistence of film domains of different thickness in an evaporating film of
      a polar liquid on a solid substrate is studied using the multiscale expansion
      technique. The propagation speed of a straight-line front is computed both in the
      quasistationary approximation and in the comoving frame. The limit of long-scale
      zigzag instability is computed. The instability is observed during evaporation
      only and exists in a range of propagation velocities bounded both from below and
      from above; during condensation, the propagating front is always stable.
      Computations for a circular front yield a critical nucleation radius for a thin
      film and confirm the anomalous dependence of the evaporation rate on the droplet
      radius observed in recent experiments.

PMID- 15447498
TI  - Initial-stage growth phenomena and distribution of local configurations of the
      restricted solid-on-solid model.
AB  - We take a detailed study on the restricted solid-on-solid (RSOS) model with
      finite nearest-neighbor height difference S. We numerically show that, for all
      finite values of S, the system belongs to the random-deposition (RD) class in the
      early time stage and then crossovers to the Kardar-Parisi-Zhang (KPZ) class. We
      find that the crossover time scales as Szeta with the crossover exponent
      zeta=2.06. Besides, we analytically study the RSOS model by grouping consecutive
      sites into local configurations to obtain the Markov chain describing the time
      evolution of the probability distribution of these local configurations. For
      demonstration, we use the RSOS model with S=2 as an explicit example and
      calculate the correlation functions and even scaling exponents based on the
      obtained probability distribution of local configurations. The results are very
      consistent with those obtained from direct simulation of the RSOS model.

PMID- 15447499
TI  - Convective instability in protein crystal growth.
AB  - The conditions for the onset of convection during protein crystalization from a
      solution are studied theoretically on the basis of diffusion-convection evolution
      equations for the concentrations coupled to the Navier-Stokes equation describing
      the flow velocity. We consider that the density of the solution depends on the
      concentration of two species, namely, a protein and a precipitating agent, a
      salt. While the protein is crystallized at the crystal/solution interface, the
      salt is rejected, and these mechanisms are described by means of boundary
      conditions for the interface. We find the base profiles for both protein and salt
      concentrations and perform a linear stability analysis of this basic state with
      regard to buoyancy induced perturbations. This gives information on the critical
      diameter of capillaries above which convection may be observed, as well as on the
      influence of the speed of growth V of the crystal interface on the stability of
      the system. Numerical integration of the model shows good agreement with the
      predictions of the linear stability analysis.

PMID- 15447500
TI  - Interfacial mixing in heteroepitaxial growth.
AB  - We investigate the growth of a film of some element B on a substrate made of
      another substance A in a model of molecular beam epitaxy. A vertical exchange
      mechanism (partial surfactant behavior) allows the A atoms to stay on the growing
      surface with a certain probability. Using kinetic Monte Carlo simulations as well
      as scaling arguments, the incorporation of the A 's into the growing B layer is
      investigated. Moreover, we develop a rate equation theory for this process. The
      concentration of A impurities decays in the B -film like (distance from the
      interface)(-1-beta), where beta approximately 0.5 for two-dimensional surfaces,
      approximately 0.8 in the one-dimensional case, and 1 in mean-field approximation.
      The power law is cut off exponentially at a characteristic thickness of the
      interdiffusion zone that depends on the rate of exchange of a B adatom with an A
      atom in the surface and on the diffusion length. Under certain conditions the
      interdiffusion zone is predicted to become narrower, if the growth temperature is
      increased.

PMID- 15447501
TI  - Statistical theory of nucleation in the presence of uncharacterized impurities.
AB  - First order phase transitions proceed via nucleation. The rate of nucleation
      varies exponentially with the free-energy barrier to nucleation, and so is highly
      sensitive to variations in this barrier. In practice, very few systems are
      absolutely pure, there are typically some impurities present which are rather
      poorly characterized. These interact with the nucleus, causing the barrier to
      vary, and so must be taken into account. Here the impurity-nucleus interactions
      are modelled by random variables. The rate then has the same form as the
      partition function of Derrida's random energy model, and as in this model there
      is a regime in which the behavior is non-self-averaging. Non-self-averaging
      nucleation is nucleation with a rate that varies significantly from one
      realization of the random variables to another. In experiment this corresponds to
      variation in the nucleation rate from one sample to another. General analytic
      expressions are obtained for the crossover from a self-averaging to a non-self
      averaging rate of nucleation.

PMID- 15447502
TI  - Dynamics and morphology of superfluid bubbles in 4He quantum crystals.
AB  - Superfluid bubbles in a 4He quantum crystal, which we refer to as quantum
      negative crystals, were investigated in bcc and hcp phases by visualizing their
      forms and motions at various temperatures. They were nearly spherical in bcc
      phase and faceted on the c-plane in their upper part in hcp phase. They steadily
      rose in the crystal due to gravity. Their direction was vertical in bcc phase and
      obliquely parallel to the c-facet in hcp phase. We also observed a slowing down
      of negative crystal in hcp phase caused by the appearance of the a-facet when
      temperature was lowered. Dynamics and morphology became successively anisotropic
      with cooling. The driving force by gravity for this motion was derived in the
      spherical case. Growth coefficient obtained by this model agreed well with the
      reported values.

PMID- 15447503
TI  - Periodic buckling of smectic-A tubular filaments in an isotropic phase.
AB  - Periodic buckling of smectic-A tubular filaments in an isotropic phase has been
      investigated both experimentally and theoretically in the binary mixture of
      octyloxycyanobiphenyl and dodecyl alcohol. As the mixture is cooled, straight
      filaments become unstable and continuously buckle by elongating at a constant
      periodicity. An analytical solution to the minimization of the curvature elastic
      energy of the smectic-A filament has been shown, and is consistent with the
      shapes of the buckled filaments. In addition, the dependence of the load on the
      length of the filament has been numerically calculated, and the critical buckling
      load of the smectic-A filament has been found to be of the order of 1 pN.

PMID- 15447505
TI  - Growth laws for the phase ordering dynamics of the B1 phase of a bent-core liquid
      crystal.
AB  - We have experimentally investigated the dynamics of the phase ordering process of
      bent-core molecules at isothermal conditions, forming the liquid crystalline
      "banana" B1 phase from the isotropic melt. In contrast to the fractal growth
      patterns observed for other "banana" liquid crystal phases, the B1 phase exhibits
      dendritic-like growth, which at short times shows similar growth structures as
      observed for conventional smectic batonnet growth. Analysis with respect to
      growth laws of the form L(t) approximately tn shows that the growth process
      follows the theoretically predicted Allen-Cahn dynamics with n=1/2 for zero
      difference in the free energy between the high- and the low-temperature phase,
      while the growth exponent approaches n-->1 for increasing supercooling. From the
      experimentally obtained data, we estimate the ratio between volume and curvature
      driven contributions to the phase ordering process as a function of supercooling
      and suggest a phenomenologically determined relationship of log DeltaF
      approximately DeltaT for the difference in free energy between the high- and the
      low-temperature phase as the quench depth is varied.

PMID- 15447506
TI  - Origin of spontaneous polarization, tilt, and chiral structure of smectic liquid
      crystal phases composed of bent-core molecules: a molecular model.
AB  - A simple molecular model is proposed for novel bent-core smectic phases that
      enables one to explain the origin of the experimentally observed chiral structure
      of the B2 phase composed of nonchiral banana-shaped molecules. It is shown that
      in the perfectly ordered smectic phase the distributed dispersion interaction
      between banana-shaped molecules stabilizes the spontaneous polarization and may
      be responsible for the tilt of the director. The orientation of the spontaneous
      polarization with respect to the tilt plane is determined by the balance between
      the dispersion and electrostatic dipole-dipole intermolecular interactions. In
      particular, sufficiently strong dipole-dipole interaction promotes the B2 phase
      where the polarization is normal to the tilt plane. The actual chiral structure
      of each smectic layer in the B2 phase appears as a result of the symmetry
      breaking. In the case of small molecular dipoles the nonchiral polar smectic
      phase is formed where the spontaneous polarization is parallel to the tilt plane.
      The role of the opening angle and of the axial ratio of banana-shaped molecules
      is also considered and a phase diagram is presented.

PMID- 15447504
TI  - Rheological properties in discotic liquid crystalline phases of 2,3,7,8,12,13
      hexa(n-tetradecanoyloxy)truxene.
AB  - Measurements of rheological properties, including the electrorheological effect,
      are made in liquid crystalline phases, discotic nematic (ND) and discotic
      disordered rectangular columnar (Drd) phases, of 2,3,7,8,12,13-hexa(n
      tetradecanoyloxy)truxene. It is found that the fluidity of the ND phase is
      Newtonian and an application of high electric field perpendicular to the flow
      direction (velocity gradient direction) causes a decrease of the viscosity. These
      results indicate that a flow alignment of the director occurs with its
      orientation near the velocity gradient direction and the signs of the Leslie
      coefficients alpha2 and alpha3 are positive. From the temperature dependence of
      alpha2, instability of the flow alignment structure in ND and Drd phases is also
      discussed.

PMID- 15447513
TI  - Exact solution of a linear molecular motor model driven by two-step fluctuations
      and subject to protein friction.
AB  - We investigate by analytical means the stochastic equations of motion of a linear
      molecular motor model based on the concept of protein friction. Solving the
      coupled Langevin equations originally proposed by Mogilner et al. [Phys. Lett. A
      237, 297 (1998)], and averaging over both the two-step internal conformational
      fluctuations and the thermal noise, we present explicit, analytical expressions
      for the average motion and the velocity-force relationship. Our results allow for
      a direct interpretation of details of this motor model which are not readily
      accessible from numerical solutions. In particular, we find that the model is
      able to predict physiologically reasonable values for the load-free motor
      velocity and the motor mobility.

PMID- 15447507
TI  - Unwrapping of DNA-protein complexes under external stretching.
AB  - A DNA-protein complex modeled by a semiflexible chain and an attractive spherical
      core is studied in the situation when an external stretching force is acting on
      one end monomer of the chain while the other end monomer is kept fixed in space.
      Without a stretching force, the chain is wrapped around the core. By applying an
      external stretching force, unwrapping of the complex is induced. We study the
      statics and dynamics of the unwrapping process by computer simulations and simple
      phenomenological theory. We find two different scenarios depending on the chain
      stiffness: For a flexible chain, the extension of the complex scales linearly
      with the external force applied. The sphere-chain complex is disordered; i.e.,
      there is no clear winding of the chain around the sphere. For a stiff chain, on
      the other hand, the complex structure is ordered, which is reminiscent of
      nucleosome. There is a clear winding number, and the unwrapping process under
      external stretching is discontinuous with jumps of the distance-force curve. This
      is associated with discrete unwinding processes of the complex. Our predictions
      are of relevance for experiments, which measure force-extension curves of DNA
      protein complexes, such as nucleosome, using optical tweezers.

PMID- 15447511
TI  - Solution of the quasispecies model for an arbitrary gene network.
AB  - In this paper, we study the equilibrium behavior of Eigen's quasispecies
      equations for an arbitrary gene network. We consider a genome consisting of N
      genes, so that the full genome sequence sigma may be written as sigma=
      sigma1sigma2...sigmaN, where sigma(i) are sequences of individual genes. We
      assume a single fitness peak model for each gene, so that gene i has some
      "master" sequence sigma(i,0) for which it is functioning. The fitness landscape
      is then determined by which genes in the genome are functioning and which are
      not. The equilibrium behavior of this model may be solved in the limit of
      infinite sequence length. The central result is that, instead of a single error
      catastrophe, the model exhibits a series of localization to delocalization
      transitions, which we term an "error cascade." As the mutation rate is increased,
      the selective advantage for maintaining functional copies of certain genes in the
      network disappears, and the population distribution delocalizes over the
      corresponding sequence spaces. The network goes through a series of such
      transitions, as more and more genes become inactivated, until eventually
      delocalization occurs over the entire genome space, resulting in a final error
      catastrophe. This model provides a criterion for determining the conditions under
      which certain genes in a genome will lose functionality due to genetic drift. It
      also provides insight into the response of gene networks to mutagens. In
      particular, it suggests an approach for determining the relative importance of
      various genes to the fitness of an organism, in a more accurate manner than the
      standard "deletion set" method. The results in this paper also have implications
      for mutational robustness and what C.O. Wilke termed "survival of the flattest."

PMID- 15447508
TI  - Solvation versus freezing in a heteropolymer globule.
AB  - We address the response of a random heteropolymer to preferential solvation of
      certain monomer types at the globule-solvent interface. For each set of monomers
      that can comprise the molecule's surface, we represent the ensemble of allowed
      configurations by a Gaussian distribution of energy levels, whose mean and
      variance depend on the set's composition. Within such a random energy model, mean
      surface composition is proportional to solvation strength under most conditions.
      The breadth of this linear response regime arises from the approximate
      statistical independence of surface and volume energies. Fluctuations play a
      crucial role in determining the excess of solvophilic monomers at the surface,
      and for a diverse set of monomer types can be overcome only by very strong
      solvent preference.

PMID- 15447509
TI  - Mean-field approaches to the totally asymmetric exclusion process with quenched
      disorder and large particles.
AB  - The process of protein synthesis in biological systems resembles a one
      dimensional driven lattice gas in which the particles (ribosomes) have spatial
      extent, covering more than one lattice site. Realistic, nonuniform gene sequences
      lead to quenched disorder in the particle hopping rates. We study the totally
      asymmetric exclusion process with large particles and quenched disorder via
      several mean-field approaches and compare the mean-field results with Monte Carlo
      simulations. Mean-field equations obtained from the literature are found to be
      reasonably effective in describing this system. A numerical technique is
      developed for computing the particle current rapidly. The mean-field approach is
      extended to include two-point correlations between adjacent sites. The two-point
      results are found to match Monte Carlo simulations more closely.

PMID- 15447510
TI  - Lateral organization of cholesterol molecules in lipid-cholesterol assemblies.
AB  - We present results of an off-lattice simulation of a two-component planar system,
      as a model for lateral organization of cholesterol molecules in lipid-cholesterol
      assemblies. We explore the existence of "superlattice" structures even in fluid
      systems, in the absence of an underlying translational long-range order, and
      study their coupling to hexatic or bond-orientational order. We discuss our
      results in context of geometric superlattice theories and "condensation
      complexes" in understanding a variety of experiments in artificial lipid
      cholesterol assemblies.

PMID- 15447514
TI  - Finite width model sequence comparison.
AB  - Sequence comparison is a widely used computational technique in modern molecular
      biology. In spite of the frequent use of sequence comparisons, the important
      problem of assigning statistical significance to a given degree of similarity is
      still outstanding. Analytical approaches to filling this gap usually make use of
      an approximation that neglects certain correlations in the disorder underlying
      the sequence comparison algorithm. Here, we use the longest common subsequence
      problem, a prototype sequence comparison problem, to analytically establish that
      this approximation does make a difference to certain sequence comparison
      statistics. In the course of establishing this difference we develop a method
      that can systematically deal with these disorder correlations.

PMID- 15447521
TI  - Suppression of ecological competition by an apex predator.
AB  - In the framework of Lotka-Volterra dynamics with evolutionary parameter
      variation, it is shown that a system of two competing species which is
      evolutionarily unstable, if left to themselves, is stabilized by a common
      predator preying on both of them. Game-theoretic implications of the results are
      also discussed.

PMID- 15447512
TI  - Coupled oscillator systems of cultured cardiac myocytes: fluctuation and scaling
      properties.
AB  - Isolated and cultured neonatal cardiac myocytes exhibit autonomous rhythmic
      contraction, and their dynamics vary dramatically depending on the extent of
      mutual coupling among individual myocytes. We study the temporal changes of
      interbeat interval series in aggregated systems of spontaneously beating cultured
      neonatal rat cardiac myocytes and observe a rich variety of complex, nonlinear
      features such as frequent alternations, bistability, and periodic spikes.
      Fluctuation analysis of the interval series reveals that there occurs a
      transition in scaling behavior from persistent correlations to antipersistent
      correlations as the coupling develops with incubation time. Additionally, we
      perform computer simulations using interacting Bonhoeffer-van der Pol oscillators
      to understand the effects of coupling on the fluctuation dynamics of each
      constituent oscillator. We find that the formation of strong and heterogeneous
      coupling among the oscillators is a key factor to yield the complexity in the
      interval series as well as in the scaling behavior.

PMID- 15447515
TI  - Solvable senescence model with positive mutations.
AB  - We build upon our previous analytical results for the Penna model of senescence
      to include positive mutations. We investigate whether a small but nonzero
      positive mutation rate gives qualitatively different results to the traditional
      Penna model in which no positive mutations are considered. We find that the high
      lifespan tail of the distribution is radically changed in structure, but that
      there is not much effect on the bulk of the population. The mortality plateau
      that we found previously for a stochastic generalization of the Penna model is
      stable to a small positive mutation rate.

PMID- 15447517
TI  - Control of cardiac function and noise from a decaying power spectrum.
AB  - Evidence is presented that adds to the debate surrounding the question: To what
      extent does neural control of cardiac output exploit noise? The transduction
      capability of cardiac afferent neurons, situated in and adjacent to the heart, is
      vital to feedback in control of cardiac function. An analysis of in situ cardiac
      afferent activity shows evidence of independent and exponentially distributed
      interspike intervals. An anatomical basis for such memoryless interspike
      intervals ultimately derives from the fact that each afferent neuron is
      associated with a field of sensory neurites, or bare nerve endings, that
      transduce local chemical and mechanical stimuli in a many-to-one fashion. As
      such, cardiac afferent neurons and their sensory neurite inputs are respectively
      modeled here by the Hodgkin-Huxley equations forced by "red" noise (decaying
      power spectrum) perturbing an otherwise constant subthreshold input. A variable
      barrier competition model is derived from these equations in order to address the
      question: How are noisy inputs being processed by sensory neurons to cause each
      spike? It is found that ion channels are responsible for significant input
      "whitening" (increased spectral power at higher frequency) through
      differentiation of the inputs. Such whitening is a means to distinguish low
      frequency control signals from otherwise red noise fluctuations. Furthermore,
      spiking occurs when backward moving averages of the whitened inputs, over a
      window of the order of the sodium activation time scale, exceed an approximately
      constant barrier.

PMID- 15447519
TI  - Augmented moment method for stochastic ensembles with delayed couplings. I.
      Langevin model.
AB  - By employing a semianalytical dynamical mean-field approximation theory
      previously proposed by the author [H. Hasegawa, Phys. Rev. E 67, 041903 (2003)],
      we have developed an augmented moment method (AMM) in order to discuss dynamics
      of an N -unit ensemble described by Langevin equations with delays. In an AMM,
      original N -dimensional stochastic delay differential equations (SDDEs) are
      transformed to infinite-dimensional deterministic DEs for means and correlations
      of local as well as global variables. Infinite-order DEs arising from the non
      Markovian property of SDDE, are terminated at the finite level m in the level-m
      AMM (AMMm), which yields (3+m)-dimensional deterministic DEs. Model calculations
      have been made for linear and nonlinear Langevin models. The stationary solution
      of AMM for the linear Langevin model with N=1 is nicely compared to the exact
      result. In the nonlinear Langevin ensemble, the synchronization is shown to be
      enhanced near the transition point between the oscillating and nonoscillating
      states. Results calculated by AMM6 are in good agreement with those obtained by
      direct simulations.

PMID- 15447520
TI  - Augmented moment method for stochastic ensembles with delayed couplings. II.
      FitzHugh-Nagumo model.
AB  - Dynamics of FitzHugh-Nagumo (FN) neuron ensembles with time-delayed couplings
      subject to white noises, has been studied by using both direct simulations and a
      semianalytical augmented moment method (AMM) which has been proposed in a
      preceding paper [H. Hasegawa, Phys. Rev. E 70, 021911 (2004)]. For N-unit FN
      neuron ensembles, AMM transforms original 2N-dimensional stochastic delay
      differential equations (SDDEs) to infinite-dimensional deterministic DEs for
      means and correlation functions of local and global variables. Infinite-order
      recursive DEs are terminated at the finite level m in the level-m AMM (AMMm),
      yielding 8(m+1)-dimensional deterministic DEs. When a single spike is applied,
      the oscillation may be induced if parameters of coupling strength, delay, noise
      intensity and/or ensemble size are appropriate. Effects of these parameters on
      the emergence of the oscillation and on the synchronization in FN neuron
      ensembles have been studied. The synchronization shows the fluctuation-induced
      enhancement at the transition between nonoscillating and oscillating states.
      Results calculated by AMM5 are in fairly good agreement with those obtained by
      direct simulations.

PMID- 15447516
TI  - Structure and fluctuations of phosphatidylcholines in the vicinity of the main
      phase transition.
AB  - We have determined the structural properties and bending fluctuations of fully
      hydrated phosphatidylcholine multibilayers in the fluid (Lalpha) phase, as well
      as the structure of the ripple (Pbeta') phase near the main phase transition
      temperature (TM) by x-ray diffraction. The number of carbons, nHC, per acyl chain
      of the studied disaturated lipids varied from 14 to 22. All lipids exhibit a
      nonlinear increase of the lamellar repeat distance d in the Lalpha phase upon
      approaching TM, known as "anomalous swelling." The nonlinear increase reduces
      with chain length, but levels off at a constant value of about 0.5 A for lipids
      with more than 18 hydrocarbons per chain. A detailed analysis shows that
      anomalous swelling has two components. One is due to an expansion of the water
      layer, which decreases with chain length and finally vanishes for nHC >18. The
      second component is due to a bilayer thickness increase, which remains unchanged
      in its temperature dependence, including a nonlinear component of about 0.5 A in
      the vicinity of TM. Thus, anomalous swelling above 18 hydrocarbons per chain is
      due to the pretransitional effects on the membrane only. These results are
      supported by a bending fluctuation analysis revealing increased undulations close
      to TM only for the short chain lipids. We have further calculated the electron
      density maps in the ripple phase and find no coupling of the magnitude of the
      ripple amplitude to the chain length effects observed in the Lalpha phase. Hence,
      in agreement with an earlier report by Mason et al. [Phys. Rev. E 63, 030902
      (2001)] there is no connection between the formation of the ripple phase and
      anomalous swelling.

PMID- 15447518
TI  - Spontaneous rhythmic motion of a polymer chain in a continuous-wave laser field.
AB  - Recently, it has been found that a giant DNA molecule exhibits a repetitive
      change in conformation between an elongated coil and folded compact states under
      irradiation by a continuous IR laser. We report here a theoretical model to
      explain such spontaneous rhythmic motion. The generation of the rhythm can be
      attributed to the competition between optical attraction in the compact state and
      the instability of the compact state at the laser focus due to heating. This
      rhythmic conformational change is discussed in relation to the working mechanism
      of biological molecular motors.

PMID- 15447522
TI  - Pulse-coupled resonate-and-fire models.
AB  - We analyze two pulse-coupled resonate-and-fire neurons. Numerical simulation
      reveals that an antiphase state is an attractor of this model. We can
      analytically explain the stability of antiphase states by means of a return map
      of firing times, which we propose in this paper. The resultant stability
      condition turns out to be quite simple. The phase diagram based on our theory
      shows that there are two types of antiphase states. One of these cannot be seen
      in coupled integrate-and-fire models and is peculiar to resonate-and-fire models.
      The results of our theory coincide with those of numerical simulations.

PMID- 15447527
TI  - Density functional theory for sphere-needle mixtures: toward finite rod
      thickness.
AB  - For mixtures of hard spheres and hard spherocylinders of large aspect ratio a
      recently proposed density functional theory is extended to incorporate effects
      due to nonvanishing rod thickness. This is accomplished by introducing several
      new geometric weight functions into the framework. We demonstrate explicitly how
      these weight functions recover the sphere-rod Mayer bond.

PMID- 15447523
TI  - Dynamics of a contact process with ontogeny.
AB  - We propose a simple model of how sessile organisms grow, disperse, and die. Our
      model extends the contact process to include a spatially explicit representation
      of organismal growth in addition to the familiar terms denoting reproduction and
      mortality. We develop a size-structured mean field theory which predicts an
      oscillatory phase as a consequence of excess reproduction. Monte Carlo
      simulations of a spatial implementation show instead a transition from a dilute
      to a ring-like phase. The ring-like phase arises as a consequence of the
      competition for limited space among juvenile and mature organisms, i.e., the
      ecological cost of reproduction. We also calculate the phase transition between
      life and death in the spatial model and find that it is in the same universality
      class as directed percolation. Finally, we analyze the onset of the ring-like
      phase via a spatial autocorrelation and comment on the model's applicability to
      problems in the study of ecosystem structure and dynamics.

PMID- 15447525
TI  - Picometer-scale dynamical observations of individual membrane proteins: the case
      of bacteriorhodopsin.
AB  - In vivo measurements of dynamical conformational changes in single biomolecules
      under functional conditions have had a tremendous impact on molecular and cell
      biology. However, even single-molecule fluorescent resonance energy transfer
      cannot easily monitor the intramolecular dynamics in cell systems due to
      shortcomings in monitoring precision. Here, we report dynamical observations of
      irreversible intramolecular conformational changes in a single-membrane protein
      [bacteriorhodopsin (BR)] using diffracted x-ray tracking. The light-driven proton
      pump BR is the best-characterized membrane protein. The position of BR's 35th
      amino acid, which is located farthest from retinal, exhibits a momentary
      positional jump of 0.73+/-0.48 A due to the expression of its function. Following
      that, we observed Brownian motion without the diffracted spots returning to their
      initial positions. The average width of this jump is about 14 times larger than
      that of thermal Brownian motion and agrees with estimated movements from known x
      ray crystallography data. This result is an important step toward realizing in
      vivo observations of single-molecular conformational changes in membrane
      proteins.

PMID- 15447528
TI  - Oscillatory phase transition and pulse propagation in noisy integrate-and-fire
      neurons.
AB  - We study nonlocally coupled noisy integrate-and-fire neurons with the Fokker
      Planck equation. A propagating pulse state and a wavy state appear as a phase
      transition from an asynchronous state. We also find a solution in which traveling
      pulses are emitted periodically from a pacemaker region.

PMID- 15447526
TI  - Competition between short-ranged attraction and short-ranged repulsion in crowded
      configurational space: aA lattice model description.
AB  - We describe a simple nearest-neighbor Ising model that is capable of supporting a
      gas, liquid, and crystal, in characteristic relationship to each other. As the
      parameters of the model are varied, one obtains characteristic patterns of phase
      behavior reminiscent of continuum systems where the range of the interaction is
      varied. The model also possesses dynamical arrest, and although we have not
      studied it in detail, these "transitions" appear to have a reasonable
      relationship to the phases and their transitions.

PMID- 15447530
TI  - Modularity from fluctuations in random graphs and complex networks.
AB  - The mechanisms by which modularity emerges in complex networks are not well
      understood but recent reports have suggested that modularity may arise from
      evolutionary selection. We show that finding the modularity of a network is
      analogous to finding the ground-state energy of a spin system. Moreover, we
      demonstrate that, due to fluctuations, stochastic network models give rise to
      modular networks. Specifically, we show both numerically and analytically that
      random graphs and scale-free networks have modularity. We argue that this fact
      must be taken into consideration to define statistically significant modularity
      in complex networks.

PMID- 15447529
TI  - Pattern formation driven by nematic ordering of assembling biopolymers.
AB  - The biopolymers actin and microtubules are often in an ongoing assembling
      disassembling state far from thermal equilibrium. Above a critical density this
      leads to spatially periodic patterns, as shown by a scaling argument and in terms
      of a phenomenological continuum model, which meets also Onsager's statistical
      theory of the nematic-to-isotropic transition in the absence of reaction
      kinetics. This pattern forming process depends much on nonlinear effects and a
      common linear stability analysis of the isotropic distribution of the filaments
      is often misleading. The wave number of the pattern decreases with the assembling
      disassembling rate and there is an uncommon discontinuous transition between the
      nematic and periodic states.

PMID- 15447524
TI  - Random walks for spike-timing-dependent plasticity.
AB  - Random walk methods are used to calculate the moments of negative image
      equilibrium distributions in synaptic weight dynamics governed by spike-timing
      dependent plasticity. The neural architecture of the model is based on the
      electrosensory lateral line lobe of mormyrid electric fish, which forms a
      negative image of the reafferent signal from the fish's own electric discharge to
      optimize detection of sensory electric fields. Of particular behavioral
      importance to the fish is the variance of the equilibrium postsynaptic potential
      in the presence of noise, which is determined by the variance of the equilibrium
      weight distribution. Recurrence relations are derived for the moments of the
      equilibrium weight distribution, for arbitrary postsynaptic potential functions
      and arbitrary learning rules. For the case of homogeneous network parameters,
      explicit closed form solutions are developed for the covariances of the synaptic
      weight and postsynaptic potential distributions.

PMID- 15447531
TI  - Universality in the level statistics of disordered systems.
AB  - Energy spectra of disordered systems share a common feature: If the entropy of
      the quenched disorder is larger than the entropy of the dynamical variables, the
      spectrum is locally that of a random energy model and the correlation between
      energy and configuration is lost. We demonstrate this effect for the Edwards
      Anderson model, but we also discuss its universality.

PMID- 15447532
TI  - Dynamical mechanisms of adaptation in multiagent systems.
AB  - We consider multiagent systems whose agents compete for resources using
      strategies with adaptable preferences. Diversity of initial preferences of
      strategies is introduced by randomly assigning virtual points to the strategies
      of each agent. When diversity increases, the successive appearance of scaling,
      kinetic sampling and waiting mechanisms shows that agent cooperation becomes
      increasingly important. Analyses yield excellent agreement with simulations over
      nine decades of data.

PMID- 15447533
TI  - Generalized minority games with adaptive trend-followers and contrarians.
AB  - We introduce a simple extension of the minority game in which the market rewards
      contrarian (respectively, trend-following) strategies when it is far from
      (respectively, close to) efficiency. The model displays a smooth crossover from a
      regime where contrarians dominate to one where trend-followers dominate. In the
      intermediate phase, the stationary state is characterized by non-Gaussian
      features as well as by the formation of sustained trends and bubbles.

PMID- 15447541
TI  - Large-scale numerical simulations of ultrametric long-range depinning.
AB  - The depinning of an elastic line interacting with a quenched disorder is studied
      for long-range interactions, applicable to in-plane crack propagation or wetting.
      An ultrametric distance is introduced instead of the Euclidean distance, allowing
      for a drastic reduction of the numerical complexity of the problem. Based on
      large-scale simulations, two to three orders of magnitude larger than previously
      considered, we obtain a very precise determination of critical exponents which
      are shown to be indistinguishable from their Euclidean metric counterparts.
      Moreover, the scaling functions are shown to be unchanged. The choice of an
      ultrametric distance thus does not affect the universality class of the depinning
      transition and opens the way to an analytic real-space renormalization-group
      approach.

PMID- 15447534
TI  - Alternative pathways of dewetting for a thin liquid two-layer film.
AB  - We consider two stacked ultrathin layers of different liquids on a solid
      substrate. Using long-wave theory, we derive coupled evolution equations for the
      free liquid-liquid and liquid-gas interfaces. Depending on the long-range van der
      Waals forces and the ratio of the layer thicknesses, the system follows different
      pathways of dewetting. The instability may be driven by varicose or zigzag modes
      and leads to film rupture either at the liquid-gas interface or at the substrate.
      We predict that the faster layer drives the evolution and may accelerate the
      rupture of the slower layer by orders of magnitude, thereby promoting the rupture
      of rather thick films.

PMID- 15447536
TI  - Dispersed phase of particles in rotating turbulent fluid flows.
AB  - Certain effects, caused by rotating turbulent fluid flows in the presence of
      gravitational force, for transport of particles dispersed in fluid are suggested
      and quantified through kinetic or probability density function approach based
      macroscopic equations. These results are exact when turbulent fluctuations in
      fluid velocity along the particle path have Gaussian distribution.

PMID- 15447535
TI  - Preparation of subharmonic patterns in nematic electroconvection.
AB  - Nematic electroconvection is studied under asymmetric periodic excitation with a
      driving electric field E(t)=E(t+T) not equal -E(t+T/2). A new dynamic regime,
      distinguished by subharmonic dynamics, is discovered in the pattern state diagram
      between conventional conductive and dielectric regimes. The spatial and temporal
      pattern characteristics are investigated experimentally. The dynamics, threshold
      fields, and selected pattern wavelengths at onset, calculated from a Floquet
      analysis of the linearized electrohydrodynamic equations with a test mode ansatz,
      are in good agreement with experimental results.

PMID- 15447537
TI  - Statistics of intense turbulent vorticity events.
AB  - We investigate statistical properties of vorticity fluctuations in fully
      developed turbulence, which are known to exhibit a strong intermittent behavior.
      Taking as the starting point the Navier-Stokes equations with a random force term
      correlated at large scales, we obtain in the high Reynolds number regime a closed
      analytical expression for the probability distribution function of an arbitrary
      component of the vorticity field. The central idea underlying the analysis
      consists in the restriction of the velocity configurational phase-space to a
      particular sector where the rate of strain and the rotation tensors can be
      locally regarded as slow and fast degrees of freedom, respectively. This
      prescription is implemented along the Martin-Siggia-Rose functional framework,
      whereby instantons and perturbations around them are taken into account within a
      steepest-descent approach.

PMID- 15447540
TI  - Anomalously slow phase transitions in self-gravitating systems.
AB  - The kinetics of collapse and explosion transitions in microcanonical self
      gravitating ensembles is analyzed. A system of point particles interacting via an
      attractive soft Coulomb potential and confined to a spherical container is
      considered. We observed that for 100-200 particles collapse takes 10(3) - 10(4)
      particle crossing times to complete; i.e., it is by two to three orders of
      magnitude slower than the velocity relaxation. In addition, it is found that the
      collapse time decreases rapidly with an increase of the soft-core radius. We
      found that such an anomalously long collapse time is caused by the slow energy
      exchange between a higher-temperature compact core and relatively cold diluted
      halo. The rate of energy exchange between the faster modes of the core particles
      and slower-moving particles of the halo is exponentially small in the ratio of
      the frequencies of these modes. As the soft-core radius increases and the typical
      core modes become slower, the ratio of core and halo frequencies decreases and
      the collapse accelerates. Implications for astrophysical systems and phase
      transition kinetics are discussed.

PMID- 15447539
TI  - Stochastic dynamical model for stock-stock correlations.
AB  - We propose a model of coupled random walks for stock-stock correlations. The
      walks in the model are coupled via a mechanism that the displacement (price
      change) of each walk (stock) is activated by the price gradients over some
      underlying network. We assume that the network has two underlying structures,
      describing the correlations among the stocks of the whole market and among those
      within individual groups, respectively, each with a coupling parameter
      controlling the degree of correlation. The model provides the interpretation of
      the features displayed in the distribution of the eigenvalues for the correlation
      matrix of real market on the level of time sequences. We verify that such
      modeling indeed gives good fitting for the market data of US stocks.

PMID- 15447538
TI  - Multipeaked polarons in soft potentials.
AB  - We consider a minimal coupled charge / excitation-lattice model capturing a
      competition between linear polaronic self-trapping and the self-focusing effects
      of a soft nonlinear on-site potential. The standard single-humped polaron ceases
      to exist above a critical value of the coupling strength, closely related to the
      inflection point in the nonlinear potential. For couplings beyond this critical
      value, we find that successive multihumped polaronic solutions correspond to the
      lowest-energy stationary states of the system, which may admit interesting
      quantum resonance behavior.

PMID- 15447542
TI  - Exponential and power-law mass distributions in brittle fragmentation.
AB  - Generic arguments, a minimal numerical model, and fragmentation experiments with
      gypsum disk are used to investigate the fragment-size distribution that results
      from dynamic brittle fragmentation. Fragmentation is initiated by random
      nucleation of cracks due to material inhomogeneities, and its dynamics are
      pictured as a process of propagating cracks that are unstable against side-branch
      formation. The initial cracks and side branches both merge mutually to form
      fragments. The side branches have a finite penetration depth as a result of
      inherent damping. Generic arguments imply that close to the minimum strain (or
      impact energy) required for fragmentation, the number of fragments of size s
      scales as s(-(2D-1)/D) f(1) (- (2/lambda)(D) s)+ f(2) (- s(-1 )(0 ) (lambda+
      s(1/D) )(D) ), where D is the Euclidean dimension of the space, lambda is the
      penetration depth, and f(1) and f(2) can be approximated by exponential
      functions. Simulation results and experiments can both be described by this
      theoretical fragment-size distribution. The typical largest fragment size s(0)
      was found to diverge at the minimum strain required for fragmentation as it is
      inversely related to the density of initially formed cracks. Our results also
      indicate that scaling of s(0) close to this divergence depends on, e.g., loading
      conditions, and thus is not universal. At the same time, the density of fragment
      surface vanishes as L-1, L being the linear dimension of the brittle solid. The
      results obtained provide an explanation as to why the fragment-size distributions
      found in nature can have two components, an exponential as well as a power-law
      component, with varying relative weights.

PMID- 15447543
TI  - Equilibrium of a confined, randomly accelerated, inelastic particle: is there
      inelastic collapse?
AB  - We consider the one-dimensional motion of a particle randomly accelerated by
      Gaussian white noise on the line segment 0<x<1. The reflections of the particle
      from the boundaries at x=0 and 1 are inelastic, with velocities just after and
      before reflection related by v(f) =-r v(i). Cornell et al. have predicted that
      the particle undergoes inelastic collapse for r< r(c) = e(-pi/sqrt[3]) =0.163,
      coming to rest at the boundary after an infinite number of collisions in a finite
      time and remaining there. This has been questioned by Florencio et al. and Anton
      on the basis of simulations. We have solved the Fokker-Planck equation satisfied
      by the equilibrium distribution function P(x,v) with a combination of exact
      analytical and numerical methods. Throughout the interval 0<r<1, P(x,v) remains
      extended, as opposed to collapsed. There is no transition in which P(x,v)
      collapses onto the boundaries. However, for r< r(c) the equilibrium boundary
      collision rate is infinite, as predicted by Cornell et al., and all moments
      [v](q);, q>0 of the velocity just after reflection from the boundary vanish.

PMID- 15447544
TI  - Perturbing general uncorrelated networks.
AB  - This paper is a direct continuation of an earlier work, where we studied Erdos
      Renyi random graphs perturbed by an interaction Hamiltonian favoring the
      formation of short cycles. Here, we generalize these results. We keep the same
      interaction Hamiltonian but let it act on general graphs with uncorrelated nodes
      and an arbitrary given degree distribution. It is shown that the results obtained
      for Erdos-Renyi graphs are generic, at the qualitative level. However, scale-free
      graphs are an exception to this general rule and exhibit a singular behavior,
      studied thoroughly in this paper, both analytically and numerically.

PMID- 15447549
TI  - Dynamical approach to the spatiotemporal aspects of the Portevin-Le Chatelier
      effect: chaos, turbulence, and band propagation.
AB  - The analysis of experimental time series, obtained from single and polycrystals
      subjected to constant strain rate tests, reports an intriguing dynamical
      crossover from a low-dimensional chaotic state at medium strain rates to an
      infinite-dimensional power-law state of stress drops at high strain rates. We
      present the results of an extensive study of all aspects of the Portevin-Le
      Chatelier (PLC) effect within the context of a recent model that reproduces this
      crossover. We characterize the dynamics of this crossover by studying the
      distribution of the Lyapunov exponents as a function of the strain rate, with
      special attention to system size effects. The distribution of the exponents
      changes from a small set of positive exponents in the chaotic regime to a dense
      set of null exponents in the scaling regime. As the latter is similar to the
      result in a shell model for turbulence, we compare the results of our model with
      that of the shell model. Interestingly, the null exponents in our model
      themselves obey a power law. The study is complimented by visualizing the
      configuration of dislocations through the slow manifold analysis. This shows that
      while a large proportion of dislocations are in the pinned state in the chaotic
      regime, most of them are pushed to the threshold of unpinning in the scaling
      regime, thus providing insight into the mechanism of crossover. We also show that
      this model qualitatively reproduces the different types of deformation bands seen
      in experiments. At high strain rates, where propagating bands are seen, the model
      equations can be reduced to the Fisher-Kolmogorov equation for propagative
      fronts, which in turn shows that the velocity of the propagation of the bands
      varies linearly with the strain rate and inversely with the dislocation density.
      These results are consistent with the known experimental results. We also discuss
      the connection between the nature of band types and the dynamics in the
      respective regimes. The analysis demonstrates that this simple dynamical model
      captures the complex spatiotemporal features of the PLC effect.

PMID- 15447546
TI  - Broadening of a nonequilibrium phase transition by extended structural defects.
AB  - We study the effects of quenched extended impurities on nonequilibrium phase
      transitions in the directed percolation universality class. We show that these
      impurities have a dramatic effect: they completely destroy the sharp phase
      transition by smearing. This is caused by rare strongly coupled spatial regions
      which can undergo the phase transition independently from the bulk system. We use
      extremal statistics to determine the stationary state as well as the dynamics in
      the tail of the smeared transition, and we illustrate the results by computer
      simulations.

PMID- 15447547
TI  - Characterization of weighted complex networks.
AB  - To account for possible distinct functional roles played by different nodes and
      links in complex networks, we introduce and analyze a class of weighted scale
      free networks. The weight of a node is assigned as a random number, based on
      which the weights of links are defined. We utilize the concept of betweenness to
      characterize the weighted networks and obtain the scaling laws governing the
      betweenness as functions both of the weight and of the degree. The scaling
      results may be useful for identifying influential nodes in terms of physical
      functions in complex networks.

PMID- 15447545
TI  - Ordinary chemical reaction process induced by a unidimensional map.
AB  - In this paper we show the results of the numerical simulation of a "standard"
      reaction process obtained by a "non standard" system: a reactant oscillator (a
      harmonic oscillator with an energy threshold) weakly interacting with a
      unidimensional tent map. According to the paper by M. Bianucci, R. Mannella, B.J.
      West, and P. Grigolini [Phys. Rev. E 51, 3002 (1995)]], the action of such a map
      on the reactant system should be equivalent, in some sense, to that of a thermal
      bath, where the values of the temperature and of the friction depend on the
      normalized correlation function and on the response function of the map. Here
      this prediction is confirmed by the numerical simulation. The numerical results
      are fitted very well by an Arrhenius law with the predicted temperature and
      friction values. Notice that this is a strict test of the theory because the
      reaction rate strongly depends on the fine level statistics, i.e., a small
      deviation in the cue of the distribution would result in a large deviation in the
      value of the rate.

PMID- 15447548
TI  - Random matrix theory analysis of cross correlations in financial markets.
AB  - We confirm universal behaviors such as eigenvalue distribution and spacings
      predicted by random matrix theory (RMT) for the cross correlation matrix of the
      daily stock prices of Tokyo Stock Exchange from 1993 to 2001, which have been
      reported for New York Stock Exchange in previous studies. It is shown that the
      random part of the eigenvalue distribution of the cross correlation matrix is
      stable even when deterministic correlations are present. Some deviations in the
      small eigenvalue statistics outside the bounds of the universality class of RMT
      are not completely explained with the deterministic correlations as proposed in
      previous studies. We study the effect of randomness on deterministic correlations
      and find that randomness causes a repulsion between deterministic eigenvalues and
      the random eigenvalues. This is interpreted as a reminiscent of "level repulsion"
      in RMT and explains some deviations from the previous studies observed in the
      market data. We also study correlated groups of issues in these markets and
      propose a refined method to identify correlated groups based on RMT. Some
      characteristic differences between properties of Tokyo Stock Exchange and New
      York Stock Exchange are found.

PMID- 15447554
TI  - Frequency synchronization in a random oscillator network.
AB  - We study the frequency synchronization of a randomly coupled oscillators. By
      analyzing the continuum limit, we obtain a sufficient condition for the mean
      field-type synchronization. We especially find that the critical coupling
      constant K becomes 0 in the random scale-free network, P(k) proportional, variant
      k(-gamma), if 2<gamma</=3. Numerical simulations in finite networks are
      consistent with this analysis.

PMID- 15447556
TI  - Criticality in aqueous solutions of 3-methylpyridine and sodium bromide.
AB  - We address a controversial issue regarding the nature of critical behavior in
      ternary electrolyte solutions of water, 3-methylpyridine, and sodium bromide.
      Earlier light-scattering studies showed an anomalous critical behavior in this
      system that was attributed to the formation of a microheterogeneous phase
      associated with ion-molecule clustering [M.A. Anisimov, J. Jacob, A. Kumar, V.A.
      Agayan, and J. V. Sengers, Phys. Rev. Lett. 85, 2336 (2000)]], while some other
      investigators subsequently found this system to exhibit ordinary Ising-like
      critical behavior. This contradiction forced us to revisit the problem and
      perform an accurate and comprehensive study of light scattering in this system
      paying attention to the achievement of thermodynamic equilibrium, hysteresis
      effects, aging, and prehistory of the samples, and a possible role of impurities.
      We show that properly aged, equilibrium samples of aqueous solutions of 3
      methylpyridine with NaBr exhibit universal Ising-like critical behavior, typical
      for other aqueous solutions. No evidence for an equilibrium microheterogeneous
      phase was found. We have been able to reproduce anomalous behavior (similar to
      that reported initially) in a fast run on a freshly prepared sample. We attribute
      the observed anomalies to mesoscopic nonequilibrium aggregates, possibly
      associated with supramolecular restructuring in aqueous solutions. To support
      this conclusion we performed a study of aqueous solutions of 3-methylpyridine
      without NaBr and have found long-living nonequilibrium states in aqueous
      solutions of 3-methylpyridine.

PMID- 15447550
TI  - Exact solution of Ising model on a small-world network.
AB  - We present an exact solution of a one-dimensional Ising chain with both nearest
      neighbor and random long-range interactions. Not surprisingly, the solution
      confirms the mean-field character of the transition. This solution also predicts
      the finite-size scaling that we observe in numerical simulations.

PMID- 15447558
TI  - Multicriticality of the three-dimensional Ising model with plaquette
      interactions: an extension of Novotny's transfer-matrix formalism.
AB  - A three-dimensional Ising model with the plaquette-type (next-nearest-neighbor
      and four-spin) interactions is investigated numerically. This extended Ising
      model, the so-called gonihedric model, was introduced by Savvidy and Wegner as a
      discretized version of the interacting (closed) surfaces without surface tension.
      The gonihedric model is notorious for its slow relaxation to the thermal
      equilibrium (glassy behavior), which deteriorates the efficiency of the Monte
      Carlo sampling. We employ the transfer-matrix (TM) method, implementing Novotny's
      idea, which enables us to treat an arbitrary number of spins N for one TM slice
      even in three dimensions. This arbitrariness admits systematic finite-size
      scaling analyses. Accepting the extended parameter space by Cirillo et al., we
      analyzed the (multi-) criticality of the gonihedric model for N</=13. Thereby, we
      found that, as first noted by Cirillo et al. analytically (cluster-variation
      method), the data are well described by the multicritical (crossover) scaling
      theory. That is, the previously reported nonstandard criticality for the
      gonihedric model is reconciled with a crossover exponent and the ordinary three
      dimensional-Ising universality class. We estimate the crossover exponent and the
      correlation-length critical exponent at the multicritical point as phi=0.6(2) and
      nu; =0.45(15), respectively.

PMID- 15447557
TI  - Critical behavior of the two-dimensional 2A-->3A, 4A--> phi binary system.
AB  - The phase transitions of the recently introduced 2A-->3A, 4A--> phi reaction
      diffusion model [G. Odor, Phys. Rev. E 69, 036112 (2004)]] are explored in two
      dimensions. This model exhibits site-occupation restriction and explicit
      diffusion of isolated particles. A reentrant phase diagram in the diffusion
      creation rate space is confirmed, in agreement with cluster mean-field and one
      dimensional results. For strong diffusion, a mean-field transition can be
      observed at zero branching rate characterized by an alpha=1/3 density decay
      exponent. In contrast, for weak diffusion the effective 2A-->3A-->4A--> phi
      reaction becomes relevant and the mean-field transition of the 2A-->3A, 2A--> phi
      model characterized by alpha=1/2 also appears for nonzero branching rates.

PMID- 15447553
TI  - Estimate of blow-up and relaxation time for self-gravitating Brownian particles
      and bacterial populations.
AB  - We determine an exact asymptotic expression of the blow-up time t(coll) for self
      gravitating Brownian particles or bacterial populations (chemotaxis) close to the
      critical point in d=3. We show that t(coll) = t(*) (eta- eta(c) )(-1/2) with t(*)
      =0.917 677 02..., where eta represents the inverse temperature (for Brownian
      particles) or the mass (for bacterial colonies), and eta(c) is the critical value
      of eta above which the system blows up. This result is in perfect agreement with
      the numerical solution of the Smoluchowski-Poisson system. We also determine the
      exact asymptotic expression of the relaxation time close to but above the
      critical temperature and derive a large time asymptotic expansion for the density
      profile exactly at the critical point.

PMID- 15447560
TI  - Spatiotemporal structures in a model with delay and diffusion.
AB  - Pattern formation described by differential-difference equations with diffusion
      is investigated. It is shown that an arbitrarily small diffusion induces space
      time turbulence just at the instability threshold of the homogeneous stationary
      solution. We prove this property by deriving a complex Ginzburg-Landau equation
      on the basis of normal form analysis. Well above threshold, such turbulent
      structures give way to synchronized states ordered by spirals and targets. This
      secondary instability can be understood with an asymptotic method representing
      the system as a cellular automaton network.

PMID- 15447552
TI  - Generalized epidemic process and tricritical dynamic percolation.
AB  - The renowned general epidemic process describes the stochastic evolution of a
      population of individuals which are either susceptible, infected, or dead. A
      second order phase transition belonging to the universality class of dynamic
      isotropic percolation lies between the endemic and pandemic behavior of the
      process. We generalize the general epidemic process by introducing a fourth kind
      of individuals, viz., individuals which are weakened by the process but not yet
      infected. This weakening gives rise to a mechanism that introduces a global
      instability in the spreading of the process and therefore opens the possibility
      of a discontinuous transition in addition to the usual continuous percolation
      transition. The tricritical point separating the lines of first and second order
      transitions constitutes an independent universality class, namely, the
      universality class of tricritical dynamic isotropic percolation. Using
      renormalized field theory we work out a detailed scaling description of this
      universality class. We calculate the scaling exponents in an epsilon expansion
      below the upper critical dimension d(c) =5 for various observables describing
      tricritical percolation clusters and their spreading properties. In a remarkable
      contrast to the usual percolation transition, the exponents beta and beta(')
      governing the two order parameters, viz., the mean density and the percolation
      probability, turn out to be different at the tricritical point. In addition to
      the scaling exponents we calculate for all our static and dynamic observables
      logarithmic corrections to the mean-field scaling behavior at d(c) =5.

PMID- 15447555
TI  - Finite-element analysis of contact between elastic self-affine surfaces.
AB  - Finite-element methods are used to study nonadhesive, frictionless contact
      between elastic solids with self-affine surfaces. We find that the total contact
      area rises linearly with the load at small loads. The mean pressure in the
      contact regions is independent of load and proportional to the root-mean-square
      slope of the surface. The constant of proportionality is nearly independent of
      the Poisson ratio and roughness exponent and lies between previous analytic
      predictions. The contact morphology is also analyzed. Connected contact regions
      have a fractal area and perimeter. The probability of finding a cluster of area
      a(c) drops as a(-tau )(c ) where tau increases with a decrease in roughness
      exponent. The distribution of pressures shows an exponential tail that is also
      found in many jammed systems. These results are contrasted to simpler models and
      experiments.

PMID- 15447559
TI  - Current statistics for wave transmission through an open Sinai billiard: effects
      of net currents.
AB  - Transport through quantum and microwave cavities is studied by analytic and
      numerical techniques. In particular, we consider the statistics for a finite net
      probability current (Poynting vector) <j> flowing through an open ballistic Sinai
      billiard to which two opposite leads/wave guides are attached. We show that if
      the net probability current is small, the scattering wave function inside the
      billiard is well approximated by a Gaussian random complex field. In this case,
      the current statistics are universal and obey simple analytic forms. For larger
      net currents, these forms still apply over several orders of magnitudes. However,
      small characteristic deviations appear in the tail regions. Although the focus is
      on electron and microwave billiards, the analysis is relevant also to other
      classical wave cavities as, for example, open planar acoustic reverberation
      rooms, elastic membranes, and water surface waves in irregularly shaped vessels.

PMID- 15447551
TI  - Combining geometrical and dynamical disorder to enhance transport.
AB  - We look for the optimal way to distribute rectifiers in order to maximize their
      effect on the transport properties of Brownian particles. These rectifiers are
      introduced in the form of flashing asymmetric potentials distributed on a one
      dimensional lattice. We study the effects that different distributions of these
      rectifiers have on the generated current and on the energy cost of transport.
      Based on both analytical and numerical results, we observe an unexpected increase
      in the efficiency of the rectifiers and the magnitude of the current for the case
      in which geometrical and dynamical disorder are combined. We show that this
      effect is a direct consequence of the "hitchhiker" or "waiting time" paradox.

PMID- 15447561
TI  - Encoding via conjugate symmetries of slow oscillations for globally coupled
      oscillators.
AB  - We study properties of the dynamics underlying slow cluster oscillations in two
      systems of five globally coupled oscillators. These slow oscillations are due to
      the appearance of structurally stable heteroclinic connections between cluster
      states in the noise-free dynamics. In the presence of low levels of noise they
      give rise to long periods of residence near cluster states interspersed with
      sudden transitions between them. Moreover, these transitions may occur between
      cluster states of the same symmetry, or between cluster states with conjugate
      symmetries given by some rearrangement of the oscillators. We consider the system
      of coupled phase oscillators studied by Hansel et al. [Phys. Rev. E 48, 3470
      (1993)] in which one can observe slow, noise-driven oscillations that occur
      between two families of two cluster periodic states; in the noise-free case there
      is a robust attracting heteroclinic cycle connecting these families. The two
      families consist of symmetric images of two inequivalent periodic orbits that
      have the same symmetry. For N=5 oscillators, one of the periodic orbits has one
      unstable direction and the other has two unstable directions. Examining the
      behavior on the unstable manifold for the two unstable directions, we observe
      that the dimensionality of the manifold can give rise to switching between
      conjugate symmetry orbits. By applying small perturbations to the system we can
      easily steer it between a number of different marginally stable attractors.
      Finally, we show that similar behavior occurs in a system of phase-energy
      oscillators that are a natural extension of the phase model to two dimensional
      oscillators. We suggest that switching between conjugate symmetries is a very
      efficient method of encoding information into a globally coupled system of
      oscillators and may therefore be a good and simple model for the neural encoding
      of information.

PMID- 15447563
TI  - Information flow through a chaotic channel: prediction and postdiction at finite
      resolution.
AB  - We reconsider the persistence of information under the dynamics of the logistic
      map in order to discuss communication through a nonlinear channel where the
      sender can set the initial state of the system with finite resolution, and the
      recipient measures it with the same accuracy. We separate out the contributions
      of global phase-space shrinkage and local-phase space contraction and expansion
      to the uncertainty in predicting and postdicting the state of the system. We
      determine how the amplification parameter, the time lag, and the resolution
      influence the possibility for communication. A novel "clockwork" representation
      for real numbers is introduced that allows for a visualization of the flow of
      information between scales.

PMID- 15447562
TI  - Spiral wave drift in an electric field and scroll wave instabilities.
AB  - Here, I present the numerical computation of speed and direction of the drift of
      a spiral wave in an excitable medium in the presence of an electric field. The
      drift speed presents a strong variation close to the parameter value where the
      drift-speed component along the field direction from parallel becomes
      antiparallel. Using a simple phenomenological model and results from a numerical
      linear stability analysis of scroll waves, I show that this behavior can be
      attributed to a resonance of the meander modes with the translation modes of the
      spiral wave. Extending this phenomenological model to scroll waves also clarifies
      the link between the drift and long wavelength instabilities of scroll waves.

PMID- 15447566
TI  - Stringent numerical test of the Poisson distribution for finite quantum
      integrable Hamiltonians.
AB  - Using a class of exactly solvable models based on the pairing interaction, we
      show that it is possible to construct integrable Hamiltonians with a Wigner
      distribution of nearest-neighbor level spacings. However, these Hamiltonians
      involve many-body interactions and the addition of a small integrable
      perturbation very quickly leads the system to a Poisson distribution. Besides
      this exceptional case, we show that the accumulated distribution of an ensemble
      of random integrable two-body pairing Hamiltonians is in perfect agreement with
      the Poisson limit. These numerical results for quantum integrable Hamiltonians
      provide a further empirical confirmation of the work of Berry and Tabor in the
      semiclassical limit.

PMID- 15447565
TI  - Global bifurcation investigation of an optimal velocity traffic model with driver
      reaction time.
AB  - We investigate an optimal velocity model which includes the reflex time of
      drivers. After an analytical study of the stability and local bifurcations of the
      steady-state solution, we apply numerical continuation techniques to investigate
      the global behavior of the system. Specifically, we find branches of oscillating
      solutions connecting Hopf bifurcation points, which may be super- or subcritical,
      depending on parameters. This analysis reveals several regions of multistability.

PMID- 15447564
TI  - Loschmidt echo for a chaotic oscillator.
AB  - Chaotic dynamics of a nonlinear oscillator is considered in the semiclassical
      approximation. The Loschmidt echo as a measure of quantum stability to a time
      dependent variation is calculated. It is shown that an exponential decay of the
      Loschmidt echo is due to a Lyapunov exponent and it has a pure classical nature.
      The Lyapunov regime is observed for a time scale which is of the power law in
      semiclassical parameter.

PMID- 15447568
TI  - Noise-aided synchronization of coupled chaotic electrochemical oscillators.
AB  - We report experimental and numerical results on noise-enhanced synchronization of
      two coupled chaotic oscillators. Enhanced synchronization is achieved through
      superimposing small-amplitude Gaussian noise on a common system parameter of the
      two chaotic oscillators. A resonancelike behavior is found: at an optimum level
      of noise, maximum synchronization is attained. The simulations show that the
      resonance behavior occurs with both identical and nonidentical oscillators.
      Noncommon (asymmetric and independent) noise does not enhance synchronization;
      common noise seems to enhance synchronization.

PMID- 15447572
TI  - Periodic precursors of nonlinear dynamical transitions.
AB  - We study the resonant response of a nonlinear system to external periodic
      perturbations. We show by numerical simulation that the periodic resonance curve
      may anticipate the dynamical instability of the unperturbed nonlinear periodic
      system, at parameter values far away from the bifurcation points. In the presence
      of noise, the buried intrinsic periodic dynamics can be picked out by analyzing
      the system's response to periodic modulation of appropriate intensity.

PMID- 15447567
TI  - Dynamics and stability of vortex-antivortex fronts in type-II superconductors.
AB  - The dynamics of vortices in type-II superconductors exhibit a variety of patterns
      whose origin is poorly understood. This is partly due to the nonlinearity of the
      vortex mobility, which gives rise to singular behavior in the vortex densities.
      Such singular behavior complicates the application of standard linear stability
      analysis. In this paper, as a first step towards dealing with these dynamical
      phenomena, we analyze the dynamical stability of a front between vortices and
      antivortices. In particular, we focus on the question of whether an instability
      of the vortex front can occur in the absence of a coupling to the temperature.
      Borrowing ideas developed for singular bacterial growth fronts, we perform an
      explicit linear stability analysis which shows that, for sufficiently large front
      velocities and in the absence of coupling to the temperature, such vortex fronts
      are stable even in the presence of in-plane anisotropy. This result differs from
      previous conclusions drawn on the basis of approximate calculations for
      stationary fronts. As our method extends to more complicated models, which could
      include coupling to the temperature or to other fields, it provides the basis for
      a more systematic stability analysis of nonlinear vortex front dynamics.

PMID- 15447570
TI  - Turbulence near cyclic fold bifurcations in birhythmic media.
AB  - We show that at the onset of a cyclic fold bifurcation, a birhythmic medium
      composed of glycolytic oscillators displays turbulent dynamics. By computing the
      largest Lyapunov exponent, the spatial correlation function, and the average
      transient lifetime, we classify it as weak turbulence of a transient nature.
      Virtual heterogeneities generating unstable fast oscillations account for the
      transient turbulence. In the presence of a wave number instability, unstable
      oscillations can be reinjected, leading to stationary turbulence. We also find
      similar turbulence in a cell cycle model. These findings suggest that weak
      turbulence may be universal in biochemical birhythmic media exhibiting cyclic
      fold bifurcations.

PMID- 15447571
TI  - Energy localization in the Peyrard-Bishop DNA model.
AB  - We study energy localization on the oscillator chain proposed by Peyrard and
      Bishop to model DNA. We search numerically for conditions with initial energy in
      a small subgroup of consecutive oscillators of a finite chain and such that the
      oscillation amplitude is small outside this subgroup on a long time scale. We use
      a localization criterion based on the information entropy and verify numerically
      that such localized excitations exist when the nonlinear dynamics of the subgroup
      oscillates with a frequency inside the reactive band of the linear chain. We
      predict a mimium value for the Morse parameter (micro>2.25) (the only parameter
      of our normalized model), in agreement with the numerical calculations (an
      estimate for the biological value is micro=6.3 ). For supercritical masses, we
      use canonical perturbation theory to expand the frequencies of the subgroup and
      we calculate an energy threshold in agreement with the numerical calculations.

PMID- 15447569
TI  - Environmental effects in the quantum-classical transition for the delta-kicked
      harmonic oscillator.
AB  - We discuss the roles of the macroscopic limit and different system-environment
      interactions in a quantum-classical transition for a chaotic system. We consider
      the kicked harmonic oscillator subject to reservoirs that correspond in the
      classical case to purely dissipative or purely diffusive behavior, a situation
      that can be implemented in ion trap experiments. In the dissipative case, we
      derive an expression for the time at which quantum and classical predictions
      become different (breaking time) and show that complete quantum-classical
      correspondence is not possible in the chaotic regime. For the diffusive
      environment we estimate the minimum value of the diffusion coefficient necessary
      to retrieve the classical limit and also show numerical evidence that, for
      diffusion below this threshold, the breaking time behaves, essentially, like that
      in the case of a system without a reservoir.

PMID- 15447573
TI  - Adaptive control of unknown unstable steady states of dynamical systems.
AB  - A simple adaptive controller based on a low-pass filter to stabilize unstable
      steady states of dynamical systems is considered. The controller is reference
      free; it does not require knowledge of the location of the fixed point in the
      phase space. A topological limitation similar to that of the delayed feedback
      controller is discussed. We show that the saddle-type steady states cannot be
      stabilized by using the conventional low-pass filter. The limitation can be
      overcome by using an unstable low-pass filter. The use of the controller is
      demonstrated for several physical models, including the pendulum driven by a
      constant torque, the Lorenz system, and an electrochemical oscillator. Linear and
      nonlinear analyses of the models are performed and the problem of the basins of
      attraction of the stabilized steady states is discussed. The robustness of the
      controller is demonstrated in experiments and numerical simulations with an
      electrochemical oscillator, the dissolution of nickel in sulfuric acid; a
      comparison of the effect of using direct and indirect variables in the control is
      made. With the use of the controller, all unstable phase-space objects are
      successfully reconstructed experimentally.

PMID- 15447574
TI  - Homogenization induced by chaotic mixing and diffusion in an oscillatory chemical
      reaction.
AB  - A model for an imperfectly mixed batch reactor with the chlorine dioxide-iodine
      malonic acid (CDIMA) reaction, with the mixing being modelled by chaotic
      advection, is considered. The reactor is assumed to be operating in oscillatory
      mode and the way in which an initial spatial perturbation becomes homogenized is
      examined. When the kinetics are such that the only stable homogeneous state is
      oscillatory then the perturbation is always entrained into these oscillations.
      The rate at which this occurs is relatively insensitive to the chemical effects,
      measured by the Damkohler number, and is comparable to the rate of homogenization
      of a passive contaminant. When both steady and oscillatory states are stable,
      spatially homogeneous states, two possibilities can occur. For the smaller
      Damkohler numbers, a localized perturbation at the steady state is homogenized
      within the background oscillations. For larger Damkohler numbers, regions of both
      oscillatory and steady behavior can co-exist for relatively long times before the
      system collapses to having the steady state everywhere. An interpretation of this
      behavior is provided by the one-dimensional Lagrangian filament model, which is
      analyzed in detail.

PMID- 15447578
TI  - Stochastic bifurcation in a driven laser system: experiment and theory.
AB  - We analyze the effects of stochastic perturbations in a physical example
      occurring as a higher-dimensional dynamical system. The physical model is that of
      a class- B laser, which is perturbed stochastically with finite noise. The effect
      of the noise perturbations on the dynamics is shown to change the qualitative
      nature of the dynamics experimentally from a stochastic periodic attractor to one
      of chaoslike behavior, or noise-induced chaos. To analyze the qualitative change,
      we apply the technique of the stochastic Frobenius-Perron operator [L. Billings
      et al., Phys. Rev. Lett. 88, 234101 (2002)] to a model of the experimental
      system. Our main result is the identification of a global mechanism to induce
      chaoslike behavior by adding stochastic perturbations in a realistic model system
      of an optics experiment. In quantifying the stochastic bifurcation, we have
      computed a transition matrix describing the probability of transport from one
      region of phase space to another, which approximates the stochastic Frobenius
      Perron operator. This mechanism depends on both the standard deviation of the
      noise and the global topology of the system. Our result pinpoints regions of
      stochastic transport whereby topological deterministic dynamics subjected to
      sufficient noise results in noise-induced chaos in both theory and experiment.

PMID- 15447580
TI  - Border-collision period-doubling scenario.
AB  - Using a one-dimensional dynamical system, representing a Poincare return map for
      dynamical systems of the Lorenz type, we investigate the border-collision period
      doubling bifurcation scenario. In contrast to the classical period-doubling
      scenario, this scenario is formed by a sequence of pairs of bifurcations, whereby
      each pair consists of a border-collision bifurcation and a pitchfork bifurcation.
      The characteristic properties of this scenario, like symmetry-breaking and
      symmetry-recovering as well as emergence of coexisting attractors and
      noninvariant attractive sets, are investigated.

PMID- 15447581
TI  - Semiclassical accuracy in phase space for regular and chaotic dynamics.
AB  - A phase-space semiclassical approximation valid to O(h) at short times is used to
      compare semiclassical accuracy for long-time and stationary observables in
      chaotic, stable, and mixed systems. Given the same level of semiclassical
      accuracy for the short time behavior, the squared semiclassical error in the
      chaotic system grows linearly in time, in contrast with quadratic growth in the
      classically stable system. In the chaotic system, the relative squared error at
      the Heisenberg time scales linearly with h(eff), allowing for unambiguous
      semiclassical determination of the eigenvalues and wave functions in the high
      energy limit, while in the stable case the eigenvalue error always remains of the
      order of a mean level spacing. For a mixed classical phase space, eigenvalues
      associated with the chaotic sea can be semiclassically computed with greater
      accuracy than the ones associated with stable islands.

PMID- 15447576
TI  - Chemical and biological activity in three-dimensional flows.
AB  - We study the dynamics of active particles advected by three-dimensional (3D) open
      incompressible flows, both analytically and numerically. We find that 3D reactive
      flows have fundamentally different dynamical features from those in 2D systems.
      In particular, we show that the reaction's productivity per reaction step can be
      enhanced, with respect to the 2D case, while the productivity per unit time in
      some 3D flows goes to zero in the limit of high mixing rates, in contrast to the
      2D behavior, in which the productivity goes to a finite constant. These
      theoretical predictions are validated by numerical simulations on a generic map
      model.

PMID- 15447579
TI  - Stabilizing the absolutely or convectively unstable homogeneous solutions of
      reaction-convection-diffusion systems.
AB  - We study the problem of stabilization of a homogeneous solution in a two-variable
      reaction-convection-diffusion one-dimensional system with oscillatory kinetics,
      in which moving or stationary patterns emerge in the absence of control. We
      propose to use a formal spatially weighted feedback control to suppress patterns
      in an absolutely or convectively unstable system and pinning control for a
      convectively unstable system. The latter approach is very effective and may
      require only one actuator to adjust feed conditions. In the former approach, the
      positive diagonal elements of the appropriate dynamics matrix are shifted to the
      left-hand part of the complex plane to ensure linear (asymptotic) stability of
      the system according to Gershgorin criterion. Moreover, we construct a controller
      that (with many actuators) will approach the global stability of the solution,
      according to Liapunov's direct method. We apply two alternative approaches to
      reveal the unstable modes: an approximate one that is based on linear stability
      analysis of an unbounded system, and an exact one that uses a traditional
      eigenstructure analysis of bounded systems. The number of required actuators
      increases dramatically with system size and with the distance from the
      bifurcation point. The methodology is developed for a system with learning cubic
      kinetics and is tested on a more realistic cross-flow reactor model.

PMID- 15447575
TI  - Simple estimation of synchronization threshold in ensembles of diffusively
      coupled chaotic systems.
AB  - In this paper, we define a simple criterion of the synchronization threshold in
      the set of coupled chaotic systems (flows or maps) with diagonal diffusive
      coupling. The condition of chaotic synchronization is determined only by two
      "parameters of order," i.e., the largest Lyapunov exponent and the coupling
      coefficient. Our approach can be applied for both regular chaotic networks and
      arrays or lattices of chaotic oscillators with irregular, arbitrarily assumed
      structure of coupling. The main idea of the synchronization stability criterion
      is based on linear analysis of the ensembles of simplest dynamical systems.
      Numerical simulations confirm that such a linear approach approximates the
      synchronization threshold with high precision.

PMID- 15447577
TI  - Quantum-mechanical research on nonlinear resonance and the problem of quantum
      chaos.
AB  - The quantum-mechanical investigation of nonlinear resonance in terms of
      approximation to moderate nonlinearity is reduced to the investigation of
      eigenfunctions and eigenvalues of the Mathieu-Schrodinger equation. The
      eigenstates of the Mathieu-Schrodinger equation are nondegenerate in a certain
      area of pumping amplitude values in the neighborhood of the classical separatrix.
      Outside this area, the system finds itself in a degenerate state for both small
      and large pumping amplitude values. Degenerate energy terms arise as a result of
      merging and branching of pairs of nondegenerate energy terms. Equations are
      obtained for finding the merging points of energy terms. These equations are
      solved by numerical methods. The main objective of this paper is to establish a
      quantum analog of the classical stochastic layer formed in the separatrix area.
      With this end in view, we consider a nonstationary quantum-mechanical problem of
      perturbation of the state of the Mathieu-Schrodinger equation. It is shown that
      in passing through the branching point the system may pass from the pure state to
      the mixed one. At multiple passages through branching points there develops the
      irreversible process of "creeping" of the system to quantum states. In that case,
      the observed population of a certain number of levels can be considered, in our
      opinion, to be a quantum analog of the stochastic layer. The number of populated
      levels is defined by a perturbation amplitude.

PMID- 15447582
TI  - Growth activity during fingering in a porous Hele-Shaw cell.
AB  - We present in this paper an experimental study of the invasion activity during
      unstable drainage in a two-dimensional random porous medium, when the (wetting)
      displaced fluid has a high viscosity with respect to that of the (nonwetting)
      displacing fluid, and for a range of almost two decades in capillary numbers
      corresponding to the transition between capillary and viscous fingering. We show
      that the invasion process takes place in an active zone within a characteristic
      screening length lambda from the tip of the most advanced finger. The invasion
      probability density is found to only depend on the distance z to the latter tip
      and to be independent of the value for the capillary number Ca. The mass density
      along the flow direction is related analytically to the invasion probability
      density, and the scaling with respect to the capillary number is consistent with
      a power law. Other quantities characteristic of the displacement process, such as
      the speed of the most advanced finger tip or the characteristic finger width, are
      also consistent with power laws of the capillary number. The link between the
      growth probability and the pressure field is studied analytically and an
      expression for the pressure in the defending fluid along the cluster is derived.
      The measured pressure is then compared with the corresponding simulated pressure
      field using this expression for the boundary condition on the cluster.

PMID- 15447587
TI  - Imploding shock wave in a fluid of hard-core particles.
AB  - We report the study of a fluid of hard-disk particles in a contracting cavity.
      Under supersonic contraction speed, a shock wave converges to the center of the
      cavity where it implodes, creating a central peak in temperature. The dynamics of
      the fluid is studied by solving the Euler and Navier-Stokes equations, as well as
      by molecular dynamics simulations and the Enskog direct simulation Monte Carlo
      method. The value of the maximum temperature reached at the center of the cavity
      is systematically investigated with the different methods which give consistent
      results. Moreover, we develop a scaling theory for the maximum temperature based
      on the self-similar solutions of Euler's equations and mean-free-path
      considerations. This scaling theory provides a comprehensive scheme for the
      interpretation of the numerical results. In addition, the effects of the
      imploding shock wave on an passively driven isomerization reaction A <= => B are
      also studied.

PMID- 15447586
TI  - Normal velocity freeze-out of the Richtmyer-Meshkov instability when a shock is
      reflected.
AB  - It is known that for some values of the initial parameters that define the
      Richtmyer-Meshkov instability, the normal velocity at the contact surface
      vanishes asymptotically in time. This phenomenon, called freeze-out, is studied
      here with an exact analytic model. The instability freeze-out, already considered
      by previous authors [K.O. Mikaelian, Phys. Fluids 6, 356 (1994), Y. Yang, Q.
      Zhang, and D.H. Sharp, Phys. Fluids 6, 1856 (1994), and A.L. Velikovich, Phys.
      Fluids 8, 1666 (1996)], is the result of a subtle interaction between the
      unstable surface and the corrugated shock fronts. In particular, it is seen that
      the transmitted shock at the contact surface plays a key role in determining the
      asymptotic behavior of the normal velocity at the contact surface. By properly
      tuning the fluids compressibilities, the density jump, and the incident shock
      Mach number, the value of the initial circulation deposited by the reflected and
      transmitted shocks at the material interface can be adjusted in such a way that
      the normal growth at the contact surface will vanish for large times. The
      conditions for this to happen are calculated exactly, by expressing the initial
      density ratio as a function of the other parameters of the problem: fluids
      compressibilities and incident shock Mach number. This is done by means of a
      linear theory model developed in a previous work [J.G. Wouchuk, Phys. Rev. E. 63,
      056303 (2001)]. A general and qualitative criterion to decide the conditions for
      freezing-out is derived, and the evolution of different cases (freeze-out and non
      freeze-out) are studied with some detail. A comparison with previous works is
      also presented.

PMID- 15447589
TI  - Measurements of the local convective heat flux in turbulent Rayleigh-Benard
      convection.
AB  - A systematic study of the local convective heat transport in turbulent thermal
      convection is carried out in small-aspect-ratio cells filled with water. The
      local convective heat flux is obtained from the simultaneous velocity and
      temperature measurements over varying Rayleigh numbers and spatial positions
      across the entire convection cell. Large fluctuations of the local convective
      heat flux are found mainly in the vertical direction and they are determined
      primarily by the thermal plumes in the system. The experiment reveals the spatial
      distribution of the local convective heat flux in a closed cell and thus settles
      a long-debated issue on how heat is transported in small-aspect-ratio cells.

PMID- 15447592
TI  - Dynamic mechanisms for apparent slip on hydrophobic surfaces.
AB  - Recent experiments [Y. Zhu and S. Granick, Phys. Rev. Lett. 87, 096105 (2001)]
      have measured a large, shear-dependent fluid slip at partially wetting fluid
      solid surfaces. We present a simple model for such a slip, motivated by the
      recent observations of nanobubbles on hydrophobic surfaces. The model considers
      the dynamic response of bubbles to change in hydrodynamic pressure, due to the
      oscillation of a solid surface. Both the compression and diffusion of gas in the
      bubbles decrease the force on the oscillating surface by a "leaking mattress"
      effect, thereby creating an apparent shear-dependent slip. With bubbles similar
      to those observed by recent atomic force microscopy, the model predicts a force
      decrease consistent with the experimental measurements of Zhu and Granick.

PMID- 15447583
TI  - Scaling and transition structure dependence on the fluid viscosity ratio in the
      selective withdrawal transition.
AB  - In the selective withdrawal experiment, fluid is withdrawn through a tube with
      its tip suspended above a two-fluid interface. At sufficiently high flow rates,
      the interface undergoes a transition so that the lower fluid is entrained with
      the upper one, forming a spout. Previous experiments address the scalings and
      similarity profiles characterizing steady states of the system near the
      transition for one combination of fluids. In the present study, we show that
      these scalings and similarity profiles extend to systems with different viscosity
      ratios. Surprisingly, we find no dependence of the scalings and similarity
      profiles on the lower fluid viscosity. We use the results of a low-Reynolds
      number flow dimensional analysis to show that for different fluid combinations
      the curves denoting the transition straw height as a function of flow rate can be
      collapsed. Finally, these results are used to argue that in the low-Reynolds
      number regime, the capillary length sets the scale for the final curvature of the
      interface before the transition.

PMID- 15447585
TI  - Drag reduction in homogeneous turbulence by scale-dependent effective viscosity.
AB  - We demonstrate, by using suitable shell models, that drag reduction in
      homogeneous turbulence is usefully discussed in terms of a scale-dependent
      effective viscosity. The essence of the phenomenon of drag reduction found in
      models that couple the velocity field to the polymers can be recaptured by an
      "equivalent" equation of motion for the velocity field alone, with a judiciously
      chosen scale-dependent effective viscosity that succinctly summarizes the
      important aspects of the interaction between the velocity and the polymer fields.
      Finally, we clarify the differences between drag reduction in homogeneous and in
      wall bounded flows.

PMID- 15447584
TI  - Direct numerical simulation of a near-field particle-laden plane turbulent jet.
AB  - The present study investigates the gas-particle two-phase flow in the turbulent
      plane jet by solving the two-dimensional and compressible flow fields numerically
      using direct-numerical-simulation technique. The flow fields are spatially
      developing, but we focus our study on the evolution of coherent vortex structures
      and dispersion patterns of particles in the near field at different Stokes
      numbers. The initial symmetric mode of flow changes its shape to the asymmetric
      mode after about three convection periods as the flow moves downstream. The
      concessive paring processes between two and three vortex structures are observed.
      The predicted mean velocity profiles show self-similar behavior and coincide well
      with previous experimental data. The profiles of turbulent intensity and Reynolds
      shear stress also display self-similar characteristics in the further downstream
      regions. The local-focusing phenomena of particles occur in the quasicoherent
      dispersion structure of particles. The higher density distribution at the outer
      boundary of large-scale vortex structure characterizes the dispersion pattern of
      particles at the Stokes numbers of order of unity. Furthermore, these particles
      disperse largely along the lateral direction and show the nonuniform distribution
      of concentration. For the particles at the Stokes number of 0.01, the dispersion
      along the lateral direction is considerable due to the small aerodynamics
      response time, but the particles are distributed evenly in the flow field.
      Particles at the Stokes numbers of 10 and 50 disperse much less along the lateral
      direction with the even density distribution. These results support the previous
      conclusions on the dispersion of particles in the free shear flows.

PMID- 15447588
TI  - Reaction front propagation in a turbulent flow.
AB  - The propagation of reaction fronts in a turbulent fluid flow is studied by direct
      numerical simulations in two space dimensions. The velocity field is obtained
      from integrating the Navier-Stokes equation in two dimensions. We investigate the
      structure of the reaction front and the enhancement of the front propagation
      speed due to turbulent mixing. Consistently with earlier theoretical, predictions
      and experiments we find two qualitatively different regimes as the Damkohler
      number-the ratio of eddy turnover times and of the characteristic chemical time
      scale-is varied, corresponding to a distributed reaction zone and thin wrinkled
      fronts.

PMID- 15447591
TI  - Synthetic turbulence, fractal interpolation, and large-eddy simulation.
AB  - Fractal interpolation has been proposed in the literature as an efficient way to
      construct closure models for the numerical solution of coarse-grained Navier
      Stokes equations. It is based on synthetically generating a scale-invariant
      subgrid-scale field and analytically evaluating its effects on large resolved
      scales. In this paper, we propose an extension of previous work by developing a
      multiaffine fractal interpolation scheme and demonstrate that it preserves not
      only the fractal dimension but also the higher-order structure functions and the
      non-Gaussian probability density function of the velocity increments. Extensive a
      priori analyses of atmospheric boundary layer measurements further reveal that
      this multiaffine closure model has the potential for satisfactory performance in
      large-eddy simulations. The pertinence of this newly proposed methodology in the
      case of passive scalars is also discussed.

PMID- 15447590
TI  - Spreading of a thin two-dimensional strip of fluid on a vertical plane:
      experiments and modeling.
AB  - We study the thin-film flow of a constant volume of silicon oil
      (polydymethilsiloxane) spreading down a vertical glass plate. The initial
      condition is generated from a horizontal fluid filament of typical diameter 0.4
      mm. Two optical diagnostic methods are used: One based on an anamorphic system,
      and the other on the Schlieren method. The first one allows for a detailed
      characterization of the early stable stage of the spreading which is used to
      estimate the thickness of the precursor film needed to model the flow. The second
      one captures the bidimensional pattern of the transversal film instability. We
      use these techniques to determine the film thickness profiles, and the evolution
      of the moving contact line, including its shape and Fourier spectra. The
      numerical simulations of the stable stage of spreading are in good quantitative
      agreement with the experimental results. We develop a model based on linear
      stability theory that predicts the evolution of the modes present in the linear
      stage of the instability.

PMID- 15447593
TI  - Simultaneous measurement of rock permeability and effective porosity using laser
      polarized noble gas NMR.
AB  - We report simultaneous measurements of the permeability and effective porosity of
      oil-reservoir rock cores using one-dimensional NMR imaging of the penetrating
      flow of laser-polarized xenon gas. The permeability result agrees well with
      industry standard techniques, whereas effective porosity is not easily determined
      by other methods. This NMR technique may have applications to the
      characterization of fluid flow in a wide variety of porous and granular media.

PMID- 15447594
TI  - Convective instability of magnetic fluids.
AB  - A theoretical investigation of the convective instability problem in the thin
      horizontal layer of a magnetic fluid heated from below is carried out. The
      effects of the relaxation time tau and the vortex (rotational) viscosity xi are
      considered and discussed. The Chebyshev pseudospectral method is employed to
      solve the eigenvalue problems and numerical calculations are carried out for a
      number of magnetic fluids and in full range of the magnetic field. A variety of
      results under gravity-free conditions are also presented and the critical
      temperature gradient are determined for a variety of situations. It is shown that
      the consideration of (xi,tau), in the stability analysis, is most effective in
      the thin layer of the fluid and at low values of Langevin parameter alpha(L).

PMID- 15447596
TI  - Analysis of L -shell line spectra with 50-ps time resolution from Mo X -pinch
      plasmas.
AB  - Mo wire X pinches typically emit several x-ray bursts from a bright spot near the
      crossing of the X -pinch wires. Streak camera images of L -shell line emission
      from Mo wire X pinches have been analyzed using a non-local thermodynamic
      equilibrium (NLTE) collisional-radiative atomic kinetics model, providing
      temperature and density profiles with approximately 50 ps time resolution over
      the approximately 350 ps x-ray bursts. In conjunction with nonspectroscopic
      measurements, the analysis is used to propose a picture of the dynamic evolution
      of the X -pinch plasma. The L -shell spectra from the first x-ray burst indicate
      an electron density near 10(22) cm(-3) and an electron temperature near 1 keV;
      subsequent x-ray bursts have L -shell spectra that indicate electron temperatures
      slightly above 1 keV and electron densities near 10(20) and 10(21) cm(-3). The
      size of the L -shell line-emitting region is estimated to be near 10 microm for
      the first x-ray burst and much larger for the later bursts. It is proposed that
      inner-shell excitation of low ionization stages of Mo in a microm -scale plasma
      region contributes to the observed radiation from the first micropinch, which
      typically emits a short burst of >3 keV radiation and has L -shell spectra
      characterized by broad spectral lines overlaying an intense continuum.

PMID- 15447595
TI  - Laboratory measurements of 0.7 GG magnetic fields generated during high-intensity
      laser interactions with dense plasmas.
AB  - We report measurements of ultrahigh magnetic fields produced during intense (
      approximately 10(20) Wcm(-2) micro m(2) ) laser interaction experiments with
      solids. We show that polarization measurements of high-order vuv laser harmonics
      generated during the interaction (up to the 15th order) suggest the existence of
      magnetic field strengths of 0.7+/-0.1 GG in the overdense plasma. Measurements
      using higher order harmonics indicate that denser regions of the plasma can be
      probed. This technique may be useful for measurements of multi- GG level magnetic
      fields which are predicted to occur at even higher intensities.

PMID- 15447598
TI  - Dust-lower-hybrid drift instabilities with dust charge fluctuations in an
      inhomogeneous dusty magnetoplasma.
AB  - Effects of a uniform magnetic field, the plasma inhomogeneity, and dust charge
      fluctuations on low-frequency dust-lower-hybrid drift waves have been
      investigated. Charging currents of electrons and ions to a spherical dust grain
      in a nonuniform magnetized dusty plasma have been calculated to study the charge
      fluctuation induced damping or growth of low-frequency drift waves. It is found
      that for strongly magnetized electrons and ions, the charge fluctuation damping
      is reduced significantly from that of an unmagnetized plasma. For sufficiently
      hot electrons, the drift wave exhibits instability in the absence of dust charge
      fluctuation damping.

PMID- 15447597
TI  - Microcanonical calculations of excess thermodynamic properties of dense binary
      systems.
AB  - We derive a formulation to calculate the excess chemical potential of a fraction
      of N1 particles interacting with N2 particles of a different species. The excess
      chemical potential is calculated numerically from first principles by coupling
      molecular dynamics and Thomas-Fermi density functional theory to take into
      account the contribution arising from the quantum electrons on the forces acting
      on the ions. The choice of this simple functional is motivated by the fact that
      the present paper is devoted to the derivation and the validation of the method
      but more complicated functionals can and will be implemented in the future. This
      method is applied in the microcanonical ensemble, the most natural ensemble for
      molecular dynamics simulations. This avoids the introduction of a thermostat in
      the simulation and thus uncontrolled modifications of the trajectories calculated
      from the forces between particles. The calculations are conducted for three
      values of the input thermodynamic quantities, energy and density, and for
      different total numbers of particles in order to examine the uncertainties due to
      finite-size effects. This method and these calculations lie the basic foundation
      to study the thermodynamic stability of dense mixtures, without any a priori
      assumption on the degree of ionization of the different species.

PMID- 15447599
TI  - Inertial range scaling in numerical turbulence with hyperviscosity.
AB  - Numerical turbulence with hyperviscosity is studied and compared with direct
      simulations using ordinary viscosity and data from wind tunnel experiments. It is
      shown that the inertial range scaling is similar in all three cases. Furthermore,
      the bottleneck effect is approximately equally broad (about one order of
      magnitude) in these cases and only its height is increased in the hyperviscous
      case-presumably as a consequence of the steeper decent of the spectrum in the
      hyperviscous subrange. The mean normalized dissipation rate is found to be in
      agreement with both wind tunnel experiments and direct simulations. The structure
      function exponents agree with the She-Leveque model. Decaying turbulence with
      hyperviscosity still gives the usual t(-1.25) decay law for the kinetic energy,
      and also the bottleneck effect is still present and about equally strong.

PMID- 15447601
TI  - Interactive dynamics of two copropagating laser beams in underdense plasmas.
AB  - The interaction of two copropagating laser beams with crossed polarization in the
      underdense plasmas has been investigated analytically with the variational
      approach and numerically. The coupled envelope equations of the two beams include
      both the relativistic mass correction and the ponderomotive force effect. It is
      found that the relativistic effect always plays the role of beam attraction,
      while the ponderomotive force can play both the beam attraction and beam
      repulsion, depending upon the beam diameters and their transverse separation. In
      certain conditions, the two beam centers oscillate transversely around a
      propagation axis. In this case, the ponderomotive effect can lead to a higher
      oscillation frequency than that accounting for the relativistic effect only. The
      interaction of two beams decreases the threshold power for self-focusing of the
      single beam. A strong self-trapping beam can channel a weak one.

PMID- 15447602
TI  - Numerical solutions to a kinetic model for the plasma-sheath problem with charge
      exchange collisions of ions.
AB  - A kinetic model of the plasma-sheath problem is presented that includes the
      effects of charge-exchange collisions of the ion. The collisions are modeled as a
      sink for accelerated ions and as a source of cold ions. Solutions are obtained by
      numerical integration of Poisson's equation from a point near the plasma midplane
      to the wall. In the quasineutral region, these solutions agree with earlier
      analytic work. As the mean free path is decreased, the current density at the
      wall decreases and the potential profile in the quasineutral region shows a
      smooth transition from a parabolic profile to a nearly cubic profile determined
      by the ion mobility. An approximate expression is found for the ion flux to the
      wall in the collisional limit.

PMID- 15447600
TI  - Dielectric response function and plasmon dispersion in a strongly coupled two
      dimensional Coulomb liquid.
AB  - We have formulated a dielectric response function for strongly coupled two
      dimensional Coulomb liquids in the T=0 quantum domain. The formulation is based
      on the classical quasilocalized charge approximation [G. Kalman and K.I. Golden,
      Phys. Rev. A 41, 5516 (1990); K.I. Golden and G. Kalman, Phys. Plasmas 7, 14
      (2000)] and extends the QLCA formalism into the quantum domain. We calculate the
      dispersion of the longitudinal plasmon mode for r(s) =10, 20, 40 and the
      resulting dispersion curves are compared with recent experimental results. We
      also conjecture the possible existence of a new high-wave-number collective
      excitation in close proximity to the right boundary of the pair continuum.

PMID- 15447603
TI  - Radial compression of protons and H3+ ions in a multiring trap for the production
      of ultralow energy antiproton beams.
AB  - Radial compression of a proton cloud was performed in a multiring trap which was
      designed to trap and cool a large number of antiprotons for the production of low
      energy ( 10-1000 eV ) antiproton beams. The resonance frequency for the radial
      compression was almost constant from 3 x 10(5) to 3 x 10(6) protons. The
      collision process of the trapped protons was also investigated to estimate the
      energy of the protons inside the trap. This technique will be applied to the
      ASACUSA experiment at the antiproton decelerator, CERN, to extract ultraslow
      antiprotons with good emittance.

PMID- 15447604
TI  - TE-TM mode coupling in two-dimensional photonic crystals composed of liquid
      crystal rods.
AB  - We theoretically demonstrate the TE-TM mode coupling in two-dimensional photonic
      crystals composed of liquid-crystal rods due to anisotropies of liquid crystals.
      In such structures, the classification of the TE and TM modes is generally
      impossible, that is, the TE-TM mode coupling occurs. Frequencies of the mode
      coupling are investigated by the plane-wave expansion method, and the mode
      coupling is discussed by transmittance calculated by the finite-difference time
      domain method. Changes of transmittance by rotating directors of liquid crystals
      are also discussed.

PMID- 15447605
TI  - Switching of discrete optical solitons in engineered waveguide arrays.
AB  - We demonstrate a simple concept for controlling nonlinear switching of discrete
      solitons in arrays of weakly coupled optical waveguides, for both cubic and
      quadratic nonlinear response. Based on the effective discrete nonlinear equations
      describing light propagation in the waveguide arrays in the tight-binding
      approximation, we demonstrate the key ideas of the array engineering by means of
      a steplike variation of the waveguide coupling. We demonstrate the digitized
      switching of a narrow input beam for up to 11 neighboring waveguides, in the case
      of the cubic nonlinearity, and up to 10 waveguides, in the case of the quadratic
      nonlinearity. We discuss our predictions in terms of the physics of the
      engineered Peierls-Nabarro (PN) potential experienced by strongly localized
      nonlinear modes in a lattice, and calculate the PN potential for the quadratic
      nonlinear array for the first time.

PMID- 15447606
TI  - Transverse modulational instability of partially incoherent soliton stripes.
AB  - Based on the Wigner distribution approach, an analysis of the effect of partial
      incoherence on the transverse instability of soliton structures in nonlinear Kerr
      media is presented. It is explicitly shown that for a Lorentzian incoherence
      spectrum the partial incoherence gives rise to a damping which counteracts, and
      tends to suppress, the transverse instability growth. However, the general
      picture is more complicated and it is shown that the effect of the partial
      incoherence depends crucially on the form of the incoherence spectrum. In fact,
      for spectra with finite rms-width, the partial incoherence may even increase both
      the growth rate and the range of unstable, transverse wave numbers.

PMID- 15447607
TI  - Analysis of the dynamics of a blue-violet Inx Ga1-x N laser with a saturable
      absorber.
AB  - We report the results of numerical investigations of the dynamical behavior of a
      blue-violet InGaN laser with a specially incorporated saturable absorber. We have
      identified the nature of the bifurcation that occurs in the device dynamics and
      also the conditions that are necessary for self-pulsating and excitable
      operations. We also demonstrate the influence of the relevant device parameters
      on the laser dynamics and show how the properties of the saturable absorber and
      its position in the device have a considerable influence on the laser behavior.
      Finally theoretical investigations of the excitable behavior and a confirmation
      of the excitability properties of an InGaN laser are presented and discussed.

PMID- 15447608
TI  - Modified geometrical optics of a smoothly inhomogeneous isotropic medium: the
      anisotropy, Berry phase, and the optical Magnus effect.
AB  - We present a modification of the geometrical optics method, which allows one to
      properly separate the complex amplitude and the phase of the wave solution.
      Appling this modification to a smoothly inhomogeneous isotropic medium, we show
      that in the first geometrical optics approximation the medium is weakly
      anisotropic. The refractive index, being dependent on the direction of the wave
      vector, contains the correction, which is proportional to the Berry geometric
      phase. Two independent eigenmodes of right-hand and left-hand circular
      polarizations exist in the medium. Their group velocities and phase velocities
      differ. The difference in the group velocities results in the shift of the rays
      of different polarizations (the optical Magnus effect). The difference in the
      phase velocities causes an increase of the Berry phase along with the
      interference of two modes leading to the familiar Rytov law about the rotation of
      the polarization plane of a wave. The theory developed suggests that both the
      optical Magnus effect and the Berry phase are accompanying nonlocal topological
      effects. In this paper the Hamilton ray equations giving a unified description
      for both of these phenomena have been derived and also a novel splitting effect
      for a ray of noncircular polarization has been predicted. Specific examples are
      also discussed.

PMID- 15447609
TI  - Resonant phenomena in nonlinearly managed lattice solitons.
AB  - The formation of nonlinearly managed spatial solitons in Kerr-type nonlinear
      media with transverse periodic modulation of the refractive index is considered.
      The phenomenon of resonant enhancement of lattice soliton amplitude oscillations
      is reported. We show how the tunable discreteness and competition between such
      characteristic scales as the beam width and the lattice period influence
      propagation dynamics and properties of breathing lattice solitons.

PMID- 15447610
TI  - Dynamics of developable cones under shear.
AB  - We identify and study a persistent structure characteristic of the post-buckling
      regime of a thin cylindrical shell subjected to axial torsion. It consists of a
      pair of developable cones ( d cones) joined by an S-shaped ridge, having a size
      of the order of the radius of the cylinder. We study its formation by applying a
      concentrated load at the center of the shell, which creates an isolated pair of d
      cones, joined by a straight ridge that progressively tilts when a torsion angle
      is imposed. We interpret this response as the equilibrium state of a pair of
      interacting d cones in the presence of an in-plane shear field, created by axial
      torsion, which tends to drive them away from each other. We find that the
      amplitude of displacement of the d cones for a given torsion angle is amplified
      by decreasing the thickness of the sheet, therefore concluding that the
      equilibrium state is the result of a balance between bending and stretching
      energies. We propose a model where the driving effect is the coupling between the
      deformation field around the d cones and the imposed shear field, while the
      stabilizing effect is the increasing bending energy of the system.

PMID- 15447611
TI  - Negative-refraction-like behavior revealed by arrays of dielectric cylinders.
AB  - We investigate the electromagnetic propagation in two-dimensional photonic
      crystals, formed by parallel dielectric cylinders embedded in a uniform medium.
      The transmission of electromagnetic waves through prism structures is calculated
      by the standard multiple scattering theory. The results demonstrate that, in
      certain frequency regimes and when the propagation inside the scattering media is
      not considered, the transmission behavior mimics the negative refraction expected
      for a left-handed material. This feature may illusively lead to the conclusion
      that a negative refraction is observed and it obeys Snell's law of negative
      refraction. Possible implications for current experimental and theoretical
      studies of negative refraction are also discussed.

PMID- 15447612
TI  - Multiple scattering of acoustic waves and porous absorbing media.
AB  - Porous media like air-saturated polymer foams with open cells, have a nontrivial
      frequency-dependent absorption that arises due to viscous and thermal effects at
      the scale of the rigid frame microstructure. In order to produce multiple
      scattering at ultrasonic frequencies, mesoscale scatterers are introduced in the
      porous medium host. The effective wave number of such a multiscale medium should
      take into account the peculiar absorption at the microscale and the multiple
      scattering at the mesoscale to describe precisely the propagation of a coherent
      acoustic wave. For this purpose, a simple model is developed. First, an
      equivalent fluid model, derived from a homogenization method, is used to describe
      the acoustic propagation in the host porous medium itself. Second, the scattering
      by the inclusions is described with a multiple scattering approximation
      (independent scattering approximation). This simple model allows to obtain the
      total effective wave number of the porous medium with mesoscale scatterers. After
      some validating results on the multiple scattering by an array of rigid cylinders
      in air, experiments on the multiple scattering by rigid cylinders embedded in a
      porous medium are presented and compared to the developed simple model.
      Incidentally, it appears that for the host medium itself, the equivalent fluid
      model is not capable to describe the high-frequency behavior whilst a multiple
      scattering approach with (thin) viscous and thermal boundary layers around the
      scatterers is accurate in the whole frequency range.

PMID- 15447613
TI  - Band theory of light localization in one-dimensional disordered systems.
AB  - A simple approach to the problem of light localization in one-dimensional system
      is presented. The role of the Bragg reflection in one-dimensional localization of
      light is discussed. Contrary to the existent viewpoint, we show that the origin
      of band gaps of regular crystals and the localization due to disorder have a
      common nature, that is, the Bragg reflection. We expand the concept of band
      structure to random systems of finite thickness L and relate the Anderson
      localization of light with the total band gap growth, which is observed in our
      computer simulation of disordered system, as L increases.

PMID- 15447614
TI  - Force evaluations in lattice Boltzmann simulations with moving boundaries in two
      dimensions.
AB  - Two techniques, based on the exchange of momentum and the integration of stress
      tensor, for the evaluation of the hydrodynamic forces in the lattice Boltzmann
      simulations are investigated on the curved and moving boundaries in two
      dimensions. The following results are obtained by numerical simulations: (i) the
      hydrodynamic forces on an inclined boundary and arc in liquid without flow
      computed by the stress-integration method agree with analytical predictions to a
      very high accuracy, while those by the momentum-exchange method have considerable
      errors for small segments; (ii) the simulation results of the sedimentation of a
      circular cylinder in a two-dimensional channel with the stress-integration method
      for hydrodynamic forces are in excellent agreement with those by a second-order
      moving finite-element method; (iii) the particle migrated from the centerline is
      found to occur in the simulations of a circular cylinder in a Poiseuille flow by
      the stress-integration method, consistent with the Segre-Silberberg effect. In
      conclusion, the stress-integration method can be a good candidate to evaluate the
      hydrodynamic forces on the elastic boundaries and moving particles in fluid.

PMID- 15447615
TI  - Monte Carlo simulations in generalized isobaric-isothermal ensembles.
AB  - We present three generalized isobaric-isothermal ensemble Monte Carlo algorithms,
      which we refer to as the multibaric-multithermal, multibaric-isothermal, and
      isobaric-multithermal algorithms. These Monte Carlo simulations perform random
      walks widely in volume space and/or in potential energy space. From only one
      simulation run, one can calculate isobaric-isothermal-ensemble averages in wide
      ranges of pressure and temperature. We demonstrate the effectiveness of these
      algorithms by applying them to the Lennard-Jones 12-6 potential system with 500
      particles.

PMID- 15447616
TI  - Evolution of time horizons in parallel and grid simulations.
AB  - We analyze the evolution of the local simulation times (LST) in parallel discrete
      event simulations. The new ingredients introduced are (i) we associate the LST
      with the nodes and not with the processing elements, and (ii) we propose to
      minimize the exchange of information between different processing elements by
      freezing the LST on the boundaries between processing elements for some time of
      processing and then releasing them by a wide-stream memory exchange between
      processing elements. The highlights of our approach are (i) it keeps the highest
      level of processor time utilization during the algorithm evolution, (ii) it takes
      a reasonable time for the memory exchange, excluding the time consuming and
      complicated process of message exchange between processors, and (iii) the
      communication between processors is decoupled from the calculations performed on
      a processor. The effectiveness of our algorithm grows with the number of nodes
      (or threads). This algorithm should be applicable for any parallel simulation
      with short-range interactions, including parallel or grid simulations of partial
      differential equations.

PMID- 15447617
TI  - Vertex dynamics during domain growth in three-state models.
AB  - Topological aspects of interfaces are studied by comparing quantitatively the
      evolving three-color patterns in three different models, such as the three-state
      voter, Potts, and extended voter models. The statistical analysis of some
      geometrical features allows us to explore the role of different elementary
      processes during distinct coarsening phenomena in the above models.

PMID- 15447618
TI  - Preferential exchange: strengthening connections in complex networks.
AB  - Many social, technological, and biological interactions involve network
      relationships whose outcome intimately depends on the structure of the network
      and on the strengths of the connections. Yet, although much information is now
      available concerning the structure of many networks, the strengths are more
      difficult to measure. Here we show that, for one particular social network,
      notably the e-mail network, a suitable measure of the strength of the connections
      can be available. We also propose a simple mechanism, based on positive feedback
      and reciprocity, that can explain the observed behavior and that hints toward
      specific dynamics of formation and reinforcement of network connections. Network
      data from contexts different from social sciences indicate that power-law, and
      generally broad, distributions of the connection strength are ubiquitous, and the
      proposed mechanism has a wide range of applicability.

PMID- 15447619
TI  - Exponents and bounds for uniform spanning trees in d dimensions.
AB  - Uniform spanning trees are a statistical model obtained by taking the set of all
      spanning trees on a given graph (such as a portion of a cubic lattice in d
      dimensions), with equal probability for each distinct tree. Some properties of
      such trees can be obtained in terms of the Laplacian matrix on the graph, by
      using Grassmann integrals. We use this to obtain exact exponents that bound those
      for the power-law decay of the probability that k distinct branches of the tree
      pass close to each of two distinct points, as the size of the lattice tends to
      infinity.

PMID- 15447620
TI  - Transient behavior of particle transport in a Brownian motor.
AB  - The transient behavior of a Brownian motor is investigated for more detailed
      particle transport occurring therein. The asymmetric nature of the time-dependent
      mean particle velocity is examined during the transition between two different
      levels of thermal noise. The possibility of current inversion is also
      investigated. It is found that the detailed shape of the asymmetric potential is
      crucial for such an inversion to occur.

PMID- 15447621
TI  - Influence of detailed line treatment on the opacity of iron plasmas in the 2p-3d
      energy region.
AB  - The transmission spectrum has been calculated using a detailed-level-accounting
      model for iron plasmas in local thermodynamic equilibrium in the 2p-3d excitation
      energy region. The calculation is motivated by the large difference between the
      theories obtained by statistical methods such as unresolved transition array and
      superconfiguration transition array and the experiment reported in the
      literature. Detailed studies have been carried out on the effects of the width of
      individual lines and configuration interaction. The results show that the
      saturation of individual lines is evident in the transmission. These effects
      should be considered carefully to obtain an accurate opacity or transmission. In
      view of the uncertainties in the experiment, rather good agreement is found
      between our theoretical result and the experiment when these effects are taken
      into account in the calculation.

PMID- 15447622
TI  - Systematic errors due to linear congruential random-number generators with the
      Swendsen-Wang algorithm: a warning.
AB  - We show that linear congruential pseudo-random-number generators can cause
      systematic errors in Monte Carlo simulations using the Swendsen-Wang algorithm,
      if the lattice size is a multiple of a very large power of 2 and one random
      number is used per bond. These systematic errors arise from correlations within a
      single bond-update half-sweep. The errors can be eliminated (or at least
      radically reduced) by updating the bonds in a random order or in an aperiodic
      manner. It also helps to use a generator of large modulus (e.g., 60 or more
      bits).

PMID- 15447623
TI  - Comment on "universality in sandpiles".
AB  - The characterization of most of the scaling properties in sandpile models relies
      on numerical simulations, which allow us to collect a large number of avalanche
      events; in lack of an accepted theoretical framework, the estimate of the
      properties of probability distributions for an infinite system is based on
      empirical methods. Within the finite-size scaling hypothesis, for example, the
      scaling of the total energy dissipation s with the area a covered by the
      avalanche should follow the simple law s approximately a (gamma(sa) ), with
      gamma(sa) marking the universality class of the model; gamma(sa) is normally
      measured from the scaling of the average value of s given a. Chessa et al. [Phys.
      Rev. E 59, 12 (1999)] introduced a new procedure to extrapolate gamma(sa) for the
      Bak-Tang-Wiesenfeld model [P. Bak, C. Tang, and K. Wiesenfeld, Phys. Rev. A 38,
      364 (1988)], which leads to a value that matches the analogous exponent obtained
      for the Manna sandpile [S.S. Manna, J. Phys. A 24, L363 (1991)], in support of
      the hypothesis of a unique universality class for the two models. This procedure
      is discussed in detail here; it is shown how the correction used by Chessa et al.
      depends on the lattice size L and disappears as L--> infinity.

PMID- 15447624
TI  - Comment on "observation of matter wave beat phenomena in the macrodomain for
      electrons moving along a magnetic field".
AB  - I show that the claim of the observation of matter wave beat phenomena in the
      classical macrodomain by Varma et al. [Phys. Rev. E 65, 026503 (2002)] is based
      on a mistaken interpretation of effects arising from multiple focusing of an
      electron beam in an axial magnetic field. I present the basic physical facts that
      mimic wavelike phenomena and suggest a classical explanation of modulations
      reported by Varma et al. Realization that the macroscopic "de Broglie wavelength"
      used by Varma et al. is the same as the focusing distance of a monoenergetic
      electron beam in the uniform magnetic field leads to a full classical explanation
      of all the effects reported by Varma et al. The reported observations are not
      evidence for any quantumlike phenomenon in the macrodomain, and their results do
      not indicate any violation of the Lorentz equation of motion.

PMID- 15447626
TI  - An endomechanical product evaluation and selection program by a healthcare
      resource management group purchasing organization.
AB  - The purpose of this report is to describe an endomechanical product evaluation
      and selection program in open surgical procedures as well as laparoscopic surgery
      designed by hospital representatives of Consorta, Inc. (Rolling Meadows,
      Illinois), a leading healthcare resource management and group purchasing
      organization, and Auto Suture/United States Surgical, (a division of Tyco
      Healthcare Group LP, Norwalk, Connecticut). In this evaluation program, twenty
      three facilities of the six Consorta shareholder partners hospitals enrolled
      surgeons to participate in this nonexperimental observational study of the
      clinical performance of endomechanical products. Performance characteristics of
      the endomechanical products produced by Auto Suture that were evaluated in 1145
      surgical procedures included clinically acceptable ratings, clinically not
      acceptable ratings, as well as superior ratings in 2988 product evaluations. In
      this endomechanical product evaluation, the surgeons found that the
      endomechanical products were clinically acceptable in 97.7% of the evaluations.
      In these endomechanical products that were judged to be clinically acceptable,
      the surgeons gave a superior rating to 20% of the products. It is important to
      emphasize that the clinically acceptable performance of laparoscopic products
      (98.1%) was very similar to that of endomechanical performance during open
      surgery (96.9%). Similarly, a superior rating of laparoscopic products that were
      judged to be clinically acceptable (22%) was comparable to that of the superior
      rating for endomechanical products that were considered to be clinically
      acceptable during open surgery (16%). The general surgeons who performed the
      majority (64.3%) of the product evaluations for the endomechanical products found
      an extremely high clinical acceptable rating in 98.2% of the evaluations. The
      obstetricians and gynecologists who performed the next highest number of
      procedures, 427 (14.3%), had a clinically acceptable rating of 97.0%. The lowest
      clinically acceptable rating (86.3%) for endomechanical products was reported by
      orthopedic surgeons who performed only 2.7% of the evaluations.

PMID- 15447627
TI  - Pressure ulcer prevention.
AB  - The purpose of this collective review is to outline the predisposing factors in
      the development of pressure ulcers and to identify a pressure ulcer prevention
      program. The most frequent sites for pressure ulcers are areas of skin overlying
      bony prominences. There are four critical factors contributing to the development
      of pressure ulcers: pressure, shearing forces, friction, and moisture. Pressure
      is now viewed as the single most important etiologic factor in pressure ulcer
      formation. Prolonged immobilization, sensory deficit, circulatory disturbances,
      and poor nutrition have been identified as important risk factors in the
      development of pressure ulcer formation. Among the clinical assessment scales
      available, only two, the Braden Scale and Norton Scale, have been tested
      extensively for reliability and/or validity. The most commonly used risk
      assessment tools for pressure ulcer formation are computerized pressure
      monitoring and measurement of laser Doppler skin blood flow. Pressure ulcers can
      predispose the patient to a variety of complications that include bacteremia,
      osteomyelitis, squamous cell carcinoma, and sinus tracts. The three components of
      pressure ulcer prevention that must be considered in any patient include
      management of incontinence, nutritional support, and pressure relief. The
      pressure relief program must be individualized for non-weight-bearing individuals
      as well as those that can bear weight. For those that can not bear weight and
      passively stand, the RENAISSANCE Mattress Replacement System is recommended for
      the immobile patient who lies supine on the bed, the stretcher, or operating room
      table. This alternating pressure system is unique because it has three separate
      cells that are not interconnected. It is specifically designed so that deflation
      of each individual cell will reach a ZERO PRESSURE during each alternating
      pressure cycle. The superiority of this system has been documented by
      comprehensive clinical studies in which this system has been compared to the
      standard hospital bed as well as to two other commercially available pressure
      relief mattresses. The most recent advance in pressure ulcer prevention is the
      development of the ALTERN8* seating system. This seating system provides regular
      periods of pressure relief and stimulation of blood flow to skin areas while
      users are seated. By offering the combination of pressure relief therapy and an
      increase in blood flow, the ALTERN8* reportedly creates an optimum pressure ulcer
      healing environment. Foam is the most commonly used material for pressure
      reduction and pressure ulcer prevention and treatment for the mobile individual.
      For those immobilized individuals who can achieve a passive standing position, a
      powered wheelchair that allows the individual to achieve a passive standing
      position is recommended. The beneficial effects of passive standing have been
      documented by comprehensive scientific studies. These benefits include reduction
      of seating pressure, decreased bone demineralization, increased blander pressure,
      enhanced orthostatic circulatory regulation, reduction in muscular tone, decrease
      in upper extremity muscle stress, and enhanced functional status in general. In
      the absence of these dynamic alternating pressure seating systems and mattresses,
      there are enormous medicolegal implications to the healthcare facility. Because
      there is not sufficient staff to provide pressure relief to rotate the patient
      every 2 hours in a hospital setting, with the exception of the intensive care
      unit, the immobile patient is prone to develop pressure ulcers. The cost of
      caring for these preventable pressure ulcers may now be as high as 60,000 dollars
      per patient. The occupational physical strain sustained by nursing personnel in
      rotating their patients has led to occupational back pain in nurses, a major
      source of morbidity in the healthcare environment.

PMID- 15447628
TI  - Mandibular reconstruction with microsurgical bone flap and dental implants.
AB  - Functional reconstruction of the mandible following resection or traumatic injury
      depends on the bony reconstruction and support dental implants. Microsurgical
      bone flaps allow the transfer of bone and soft tissue with a rich vascular supply
      and provide a firm basis for placement of dental implants in mandible
      reconstruction. Endosseous dental implants may improve functional restoration by
      ensuring the stable dentition essential for normal mastication and speech. In
      this review article, donor sites of microsurgical bone flaps, criteria for
      placement of dental implants, timing for dental implantation, bone resorption,
      role of radiotherapy and hyperbaric oxygen, and success rate of dental implants
      are discussed.

PMID- 15447629
TI  - Photoprotection by sunscreens with topical antioxidants and systemic antioxidants
      to reduce sun exposure.
AB  - Skin cancer is the most common cancer diagnosed in the United States, and its
      incidence continues to rise. Epidemiological studies have documented that
      excessive sun exposure increases the risk of developing nonmelanoma skin cancer.
      Consequently, it is mandatory that the skin be protected from the damage that
      occurs from ultraviolet (UV) exposure. It is the purpose of this report to review
      the scientific basis for photoprotection by sunscreens, topical antioxidants, and
      systemic antioxidants to minimize the harmful effect of sun exposure. The US Food
      and Drug Administration regulates sunscreen products as over-the-counter drugs.
      Sunscreens are chemical or organic UV absorbers and nonchemical or inorganic UV
      absorbers. Other important sunscreen considerations include the sunscreen
      vehicle, sunscreen photostability, sunscreen preservatives, and sunscreen
      photoallergy and phototoxicity. Topical and systemic antioxidants have now been
      shown to supplement the photoprotective effects of sunscreen. The Skin Cancer
      Foundation, the only national and international nonprofit organization concerned
      exclusively with cancer of the skin, is playing a leadership role in eliminating
      skin cancer in our world.

PMID- 15447630
TI  - Expression, purification, characterization and structure of Pseudomonas
      aeruginosa arylamine N-acetyltransferase.
AB  - The gene for NAT (arylamine N-acetyltransferase) from Pseudomonas aeruginosa
      (panat) has been cloned from genomic DNA, and the gene product (PANAT) expressed
      as an N-terminal histidine-tagged protein in Escherichia coli and purified via
      nickel ion affinity chromatography. The specific activities of PANAT against a
      broad range of substrates have been investigated and compared with those of other
      prokaryotic NAT enzymes. For most arylamine substrates identified, PANAT exhibits
      in vitro specific activities typically one order of magnitude greater than those
      of recombinant NAT enzymes from Mycobacterium smegmatis or Salmonella
      typhimurium. Among the substrates of PANAT so far identified are the anti
      tubercular drug isoniazid, 5-aminosalicylate (a drug used in the treatment of
      inflammatory bowel disease), as well as important environmental pollutants such
      as 3,4-dichloroaniline and 2-aminofluorene. As well as acetylating common NAT
      substrates, PANAT is unique among the prokaryotic NATs so far studied in
      acetylating the folate precursor 4-aminobenzoic acid and the folate catabolite 4
      aminobenzoylglutamate. The recombinant protein has been expressed in sufficient
      quantity to allow protein crystallization, and we have subsequently determined
      the 1.95 A structure of PANAT by X-ray crystallography.

PMID- 15447631
TI  - Specific interactions of PP2A and PP2A-like phosphatases with the yeast PTPA
      homologues, Ypa1 and Ypa2.
AB  - To elucidate the specific biological role of the yeast homologues of PTPA
      (phosphatase 2A phosphatase activator), Ypa1 and Ypa2 (where Ypa stands for yeast
      phosphatase activator), in the regulation of PP2A (protein phosphatase 2A), we
      investigated the physical interaction of both Ypa proteins with the catalytic
      subunit of the different yeast PP2A-like phosphatases. Ypa1 interacts
      specifically with Pph3, Sit4 and Ppg1, whereas Ypa2 binds to Pph21 and Pph22. The
      Ypa1 and Ypa2 proteins do not compete with Tap42 (PP2A associating protein) for
      binding to PP2A family members. The interaction of the Ypa proteins with the
      catalytic subunit of PP2A-like phosphatases is direct and independent of other
      regulatory subunits, implicating a specific function for the different PP2A-Ypa
      complexes. Strikingly, the interaction of Ypa2 with yeast PP2A is promoted by the
      presence of Ypa1, suggesting a positive role of Ypa1 in the regulation of PP2A
      association with other interacting proteins. As in the mammalian system, all
      yeast PP2A-like enzymes associate as an inactive complex with Yme (yeast methyl
      esterase). Ypa1 as well as Ypa2 can reactivate all these inactive complexes,
      except Pph22-Yme. Ypa1 is the most potent activator of PP2A activity, suggesting
      that there is no direct correlation between activation potential and binding
      capacity.

PMID- 15447632
TI  - Substrate and product specificities of cis-type undecaprenyl pyrophosphate
      synthase.
AB  - UPPS (undecaprenyl pyrophosphate synthase) catalyses consecutive condensation
      reactions of FPP (farnesyl pyrophosphate) with eight isopentenyl pyrophosphates
      to generate C55 UPP, which serves as a lipid carrier for bacterial peptidoglycan
      biosynthesis. We reported the co-crystal structure of Escherichia coli UPPS in
      complex with FPP. Its phosphate head-group is bound to positively charged
      arginine residues and the hydrocarbon moiety interacts with hydrophobic amino
      acids including L85, L88 and F89, located on the alpha3 helix of UPPS. We now
      show that the monophosphate analogue of FPP binds UPPS with an eight times lower
      affinity (K(d)=4.4 microM) compared with the pyrophosphate analogue, a result of
      a larger dissociation rate constant (k(off)=192 s(-1)). Farnesol (1 mM) lacking
      the pyrophosphate does not inhibit the UPPS reaction. GGPP (geranylgeranyl
      pyrophosphate) containing a larger C20 hydrocarbon tail is an equally good
      substrate (K(m)=0.3 microM and kcat=2.1 s(-1)) compared with FPP. The shorter C10
      GPP (geranyl pyrophosphate) displays a 90-fold larger K(m) value (36.0+/-0.1
      microM) but similar kcat value (1.7+/-0.1 s(-1)) compared with FPP. Replacement
      of L85, L88 or F89 with Ala increases FPP and GGPP K(m) values by the same
      amount, indicating that these amino acids are important for substrate binding,
      but do not determine substrate specificity. With GGPP as a substrate, UPPS still
      catalyses eight isopentenyl pyrophosphate condensation reactions to synthesize
      C60 product. Computer modelling suggests that the upper portion of the active
      site tunnel, where cis double bonds of the product reside, may be critical for
      determining the final product chain length.

PMID- 15447633
TI  - Evaluating evidence of psychological adaptation: how do we know one when we see
      one?
AB  - Evolutionary psychologists argue that human nature contains many discrete
      psychological adaptations. Each adaptation is theorized to have been functional
      in humans' ancestral past, and empirical evidence that an attribute is an
      adaptation can come from showing it possesses complexity, efficiency,
      universality, and other features of special design. In this article, we present a
      tutorial review of the evidentiary forms that evolutionary psychologists commonly
      use to document the existence of human adaptations. We also present a heuristic
      framework for integrating and evaluating cross-disciplinary evidence of
      adaptation. Pregnancy sickness, incest avoidance, men's desires for multiple sex
      partners, and an easily learned fear of snakes are evaluated as possible human
      adaptations using this framework. We conclude that future research and teaching
      in evolutionary psychology would benefit from more fully utilizing cross
      disciplinary frameworks to evaluate evidence of human adaptation.

PMID- 15447634
TI  - Attentional modulation of visual processing in adult dyslexia: a spatial-cuing
      deficit.
AB  - Anumber of researchers have suggested that deficient visual attention may play a
      causal role in dyslexia. However, traditional methods for investigating this
      assertion have been limited by the conflation of sensory and attentional factors
      and the inability to isolate large attentional effects. In this study, we sought
      to overcome these problems by combining spatial cuing with a visual search task
      measuring psychophysical thresholds. In normal readers, uncued search performance
      was characterized by a strong dependence on the number of elements in the
      stimulus array. Cuing the location of the target removed much of this effect,
      suggesting attentional facilitation of performance. Although dyslexic
      participants' performance in uncued search was nearly identical to that of normal
      readers, all dyslexic participants failed to gain the same effect of cuing that
      normal readers did. However, dyslexic participants did not differ from normal
      readers on tests of magnocellular function, suggesting that this spatial-cuing
      deficit is not merely a secondary consequence of magnocellular dysfunction.

PMID- 15447635
TI  - Neural evidence that vivid imagining can lead to false remembering.
AB  - The imperfect nature of memory is highlighted by the regularity with which people
      fail to remember, or worse, remember something that never happened. We
      investigated the formation of a particular type of erroneous memory by monitoring
      brain activity using functional magnetic resonance imaging during the
      presentation of words and photos. Participants generated a visual image of a
      common object in response to each word. Subsequently, they sometimes claimed to
      have seen photos of specific objects they had imagined but not actually seen. In
      precuneus and inferior parietal regions of the cerebral cortex, activations in
      response to words were greater when participants subsequently claimed to have
      seen the corresponding object than when a false memory for that object was not
      subsequently produced. These findings indicate that brain activity reflecting the
      engagement of visual imagery can lead to falsely remembering something that was
      only imagined.

PMID- 15447636
TI  - The equivalence of learning paths in early science instruction: effect of direct
      instruction and discovery learning.
AB  - In a study with 112 third- and fourth-grade children, we measured the relative
      effectiveness of discovery learning and direct instruction at two points in the
      learning process: (a) during the initial acquisition of the basic cognitive
      objective (a procedure for designing and interpreting simple, unconfounded
      experiments) and (b) during the subsequent transfer and application of this basic
      skill to more diffuse and authentic reasoning associated with the evaluation of
      science-fair posters. We found not only that many more children learned from
      direct instruction than from discovery learning, but also that when asked to make
      broader, richer scientific judgments, the many children who learned about
      experimental design from direct instruction performed as well as those few
      children who discovered the method on their own. These results challenge
      predictions derived from the presumed superiority of discovery approaches in
      teaching young children basic procedures for early scientific investigations.

PMID- 15447637
TI  - Rejection sensitivity and the defensive motivational system: insights from the
      startle response to rejection cues.
AB  - Rejection sensitivity (RS) is the disposition to anxiously expect, readily
      perceive, and intensely react to rejection. This study used the startle probe
      paradigm to test whether the affect-based defensive motivational system is
      automatically activated by rejection cues in people who are high in RS. Stimuli
      were representational paintings depicting rejection (by Hopper) and acceptance
      (by Renoir), as well as nonrepresentational paintings of either negative or
      positive valence (by Rothko and Miro, respectively). Eyeblink startle magnitude
      was potentiated in people high in RS when they viewed rejection themes, compared
      with when they viewed nonrepresentational negative themes. Startle magnitude was
      not attenuated during viewing of acceptance themes in comparison with
      nonrepresentational positive themes. Overall, the results provide evidence that
      for people high in RS, rejection cues automatically activate the defensive
      motivational system, but acceptance cues do not automatically activate the
      appetitive motivational system.

PMID- 15447638
TI  - The influence of Afrocentric facial features in criminal sentencing.
AB  - Prior research has shown that within a racial category, people with more
      Afrocentric facial features are presumed more likely to have traits that are
      stereotypic of Black Americans compared with people with less Afrocentric
      features. The present study investigated whether this form of feature-based
      stereotyping might be observed in criminal-sentencing decisions. Analysis of a
      random sample of inmate records showed that Black and White inmates, given
      equivalent criminal histories, received roughly equivalent sentences. However,
      within each race, inmates with more Afrocentric features received harsher
      sentences than those with less Afrocentric features. These results are consistent
      with laboratory findings, and they suggest that although racial stereotyping as a
      function of racial category has been successfully removed from sentencing
      decisions, racial stereotyping based on the facial features of the offender is a
      form of bias that is largely overlooked.

PMID- 15447639
TI  - Intact conceptual priming in the absence of declarative memory.
AB  - Priming is an unconscious (nondeclarative) form of memory whereby identification
      or production of an item is improved by an earlier encounter. It has been
      proposed that declarative memory and priming might be related-for example, that
      conceptual priming results in more fluent processing, thereby providing a basis
      for familiarity judgments. In two experiments, we assessed conceptual priming and
      recognition memory across a 5-min interval in 5 memory-impaired patients. All
      patients exhibited fully intact priming in tests of both free association (study
      tent; at test, provide an association to canvas) and category verification (study
      lemon; at test, decide: Is lemon a type of fruit?). Yet the 2 most severely
      amnesic patients performed at chance on matched tests of recognition memory.
      These findings count against the notion that conceptual priming provides feelings
      of familiarity that can support accurate recognition judgments. We suggest that
      priming is inaccessible to conscious awareness and does not influence declarative
      memory.

PMID- 15447640
TI  - Linguistic markers of psychological change surrounding September 11, 2001.
AB  - The diaries of 1,084 U.S. users of an on-line journaling service were downloaded
      for a period of 4 months spanning the 2 months prior to and after the September
      11 attacks. Linguistic analyses of the journal entries revealed pronounced
      psychological changes in response to the attacks. In the short term, participants
      expressed more negative emotions, were more cognitively and socially engaged, and
      wrote with greater psychological distance. After 2 weeks, their moods and social
      referencing returned to baseline, and their use of cognitive-analytic words
      dropped below baseline. Over the next 6 weeks, social referencing decreased, and
      psychological distancing remained elevated relative to baseline. Although the
      effects were generally stronger for individuals highly preoccupied with September
      11, even participants who hardly wrote about the events showed comparable
      language changes. This study bypasses many of the methodological obstacles of
      trauma research and provides a fine-grained analysis of the time line of human
      coping with upheaval.

PMID- 15447641
TI  - Trust in testimony: children's use of true and false statements.
AB  - The extent to which young children monitor and use the truth of assertions to
      gauge the reliability of subsequent testimony was examined. Three- and 4-year-old
      children were presented with two informants, an accurate labeler and an
      inaccurate labeler. They were then invited to learn names for novel objects from
      these informants. The children correctly monitored and identified the informants
      on the basis of the truth of their prior labeling. Furthermore, children who
      explicitly identified the unreliable or reliable informant across two tasks went
      on to demonstrate selective trust in the novel information provided by the
      previously reliable informant. Children who did not consistently identify the
      unreliable or reliable informant proved indiscriminate.

PMID- 15447642
TI  - Toddlers' responsive imitation predicts preschool-age conscience.
AB  - Imitation has long been considered a mechanism for the development of conscience.
      Despite the central role of imitation in theories of moral internalization, the
      prediction from imitation to moral behavior has not been tested using an
      individual differences approach. In a longitudinal design, we examined whether
      individual differences in toddlers' responsive imitation predict preschool-age
      conscience. Mothers modeled actions for their children to imitate, and both
      matching behavior and motivation were observed at 14 and 22 months of age. We
      also measured preschool conscience by observing children's internalized conduct
      and guilt at ages 33 and 45 months. Imitation measures consistently predicted
      conscience variables. These relations were strengthened by aggregation across
      measures and times of assessment. Motivation and matching behavior each
      contributed independent variance in predicting preschool-age conscience. Results
      are consistent with the claim that responsive imitation reflects a general
      receptive stance to parents' guidance, and with both neopsychoanalytic and social
      cognitive views of imitation's importance in early moral development.

PMID- 15447643
TI  - Microsaccade orientation supports attentional enhancement opposite a peripheral
      cue: commentary on Tse, Sheinberg, and Logothetis (2003).

PMID- 15447645
TI  - Cambial meristem dormancy in trees involves extensive remodelling of the
      transcriptome.
AB  - The establishment of the dormant state in meristems involves considerable
      physiological and metabolic alterations necessary for surviving unfavourable
      growth conditions. However, a global molecular analysis of dormancy in meristems
      has been hampered by the difficulty in isolating meristem cells. We used
      cryosectioning to isolate purified cambial meristem cells from the woody plant
      Populus tremula during active growth and dormancy. These samples were used to
      generate meristem-specific cDNA libraries and for cDNA microarray experiments to
      define the global transcriptional changes underlying cambial dormancy. The
      results indicate a significant reduction in the complexity of the cambial
      transcriptome in the dormant state. Although cell division is terminated in the
      dormant cambium, the cell cycle machinery appears to be maintained in a skeletal
      state as suggested by the continued presence of transcripts for several cell
      cycle regulators. The downregulation of PttPIN1 and PttPIN2 transcripts explains
      the reduced basipetal polar auxin transport during dormancy. The induction of a
      member of the SINA family of ubiquitin ligases implicated in auxin signalling
      indicates a potential mechanism for modulation of auxin sensitivity during
      cambial dormancy. The metabolic alterations during dormancy are mirrored in the
      induction of genes involved in starch breakdown and the glyoxysomal cycle.
      Interestingly, the induction of RGA1 like gene suggests modification of
      gibberellin signalling in cambial dormancy. The induction of genes such as poplar
      orthologues of FIE and HAP2 indicates a potential role for these global
      regulators of transcription in orchestrating extensive changes in gene expression
      during dormancy.

PMID- 15447646
TI  - Regulation of carotenoid biosynthesis in plants: evidence for a key role of
      hydroxymethylbutenyl diphosphate reductase in controlling the supply of
      plastidial isoprenoid precursors.
AB  - Carotenoids are isoprenoid pigments that function as photoprotectors, precursors
      of the hormone abscisic acid (ABA), colorants and nutraceuticals. A major problem
      for the metabolic engineering of high carotenoid levels in plants is the limited
      supply of their isoprenoid precursor geranylgeranyl diphosphate (GGPP), formed by
      condensation of isopentenyl diphosphate (IPP) and dimethylallyl diphosphate
      (DMAPP) units usually synthesized by the methylerythritol phosphate (MEP) pathway
      in plastids. Our earlier work with three of the seven MEP pathway enzymes
      suggested that the first reaction of the pathway catalyzed by deoxyxylulose 5
      phosphate synthase (DXS) is limiting for carotenoid biosynthesis during tomato
      (Lycopersicon esculentum) fruit ripening. Here we investigate the contribution of
      the enzyme hydroxymethylbutenyl diphosphate reductase (HDR), which simultaneously
      synthesizes IPP and DMAPP in the last step of the pathway. A strong upregulation
      of HDR gene expression was observed in correlation with carotenoid production
      during both tomato fruit ripening and Arabidopsis thaliana seedling deetiolation.
      Constitutive overexpression of the tomato cDNA encoding HDR in Arabidopsis did
      not increase carotenoid levels in etioplasts. By contrast, light-grown transgenic
      plants showed higher carotenoid levels and an enhanced seed dormancy phenotype
      suggestive of increased ABA levels. The analysis of double transgenic Arabidopsis
      plants overproducing both the enzyme taxadiene synthase (which catalyzes the
      production of the non-native isoprenoid taxadiene from GGPP) and either HDR or
      DXS showed a twofold stronger effect of HDR in increasing taxadiene levels.
      Together, the data support a major role for HDR in controlling the production of
      MEP-derived precursors for plastid isoprenoid biosynthesis.

PMID- 15447647
TI  - A key role for ALD1 in activation of local and systemic defenses in Arabidopsis.
AB  - The Arabidopsis thaliana agd2-like defense response protein1 (ald1) mutant was
      previously found to be hypersusceptible to the virulent bacterial pathogen
      Pseudomonas syringae and had reduced accumulation of the defense signal salicylic
      acid (SA). ALD1 was shown to possess aminotransferase activity in vitro,
      suggesting it generates an amino acid-derived defense signal. We now find ALD1 to
      be a key defense component that acts in multiple contexts and partially requires
      the PHYTOALEXIN DEFICIENT4 (PAD4) defense regulatory gene for its expression in
      response to infection. ald1 plants have increased susceptibility to avirulent P.
      syringae strains, are unable to activate systemic acquired resistance and are
      compromised for resistance to the oomycete pathogen Peronospora parasitica in
      mutants with constitutively active defenses. ALD1 and PAD4 can act additively to
      control SA, PATHOGENESIS RELATED GENE1 (PR1) transcript and camalexin (an
      antimicrobial metabolite) accumulation as well as disease resistance. Finally,
      ALD1 and PAD4 can mutually affect each other's expression in a constitutive
      defense mutant, suggesting that these two genes can act in a signal amplification
      loop.

PMID- 15447648
TI  - Expression of RPS4 in tobacco induces an AvrRps4-independent HR that requires
      EDS1, SGT1 and HSP90.
AB  - The Arabidopsis RPS4 gene belongs to the Toll/interleukin-1 receptor/nucleotide
      binding site/leucine-rich repeat (TIR-NB-LRR) class of plant resistance (R)
      genes. It confers resistance to Pseudomonas syringae carrying the avirulence gene
      avrRps4. Transient expression of genomic RPS4 driven by the 35S promoter in
      tobacco leaves induces an AvrRps4-independent hypersensitive response (HR). The
      same phenotype is seen after expression of a full-length RPS4 cDNA. This
      indicates that alternative splicing of RPS4 is not involved in this HR. The
      extent of HR is correlated with RPS4 protein levels. Deletion analyses of RPS4
      domains show the TIR domain is required for the HR phenotype. Mutations in the P
      loop motif of the NB domain abolish the HR. Using virus-induced gene silencing,
      we found that the cell death resulting from RPS4 expression is dependent on the
      three plant signalling components EDS1, SGT1 and HSP90. All these data suggest
      that heterologous expression of an R gene can result in activation of cell death
      even in the absence of its cognate avirulence product, and provides a system for
      studying the RPS4 domains required for HR.

PMID- 15447649
TI  - Overexpression of the plasma membrane-localized NDR1 protein results in enhanced
      bacterial disease resistance in Arabidopsis thaliana.
AB  - Previous studies have established that mutations in the NDR1 gene in Arabidopsis
      thaliana suppress the resistance response of three resistance proteins, RPS2,
      RPM1, and RPS5, to Pseudomonas syringae pv. tomato (Pst) strain DC3000 containing
      the cognate effector genes, avrRpt2, avrRpm1, and avrpPhB, respectively. NDR1 is
      a plasma membrane (PM)-localized protein, and undergoes several post
      translational modifications including carboxy-terminal processing and N-linked
      glycosylation. Expression of NDR1 under the NDR1 native promoter complements the
      ndr1-1 mutation, while overexpression of NDR1 results in enhanced resistance to
      virulent Pst. Sequence analysis and mass spectrometry suggest that NDR1 is
      localized to the PM via a C-terminal glycosylphosphatidyl-inositol (GPI) anchor.
      GPI modification would potentially place NDR1 on the outer surface of the PM,
      perhaps allowing NDR1 to act as a transducer of pathogen signals and/or interact
      directly with the pathogen.

PMID- 15447650
TI  - The composition of newly synthesized proteins in the endoplasmic reticulum
      determines the transport pathways of soybean seed storage proteins.
AB  - Glycinin (11S) and beta-conglycinin (7S) are major storage proteins in soybean
      (Glycine max L.) seeds and accumulate in the protein storage vacuole (PSV). These
      proteins are synthesized in the endoplasmic reticulum (ER) and transported to the
      PSV by vesicles. Electron microscopic analysis of developing soybean cotyledons
      of the wild type and mutants with storage protein composition different from that
      of the wild type showed that there are two transport pathways: one is via the
      Golgi and the other bypasses it. Golgi-derived vesicles were observed in all
      lines used in this study and formed smooth dense bodies with a diameter of 0.5 to
      several micrometers. ER-derived protein bodies (PBs) with a diameter of 0.3-0.5
      microm were observed at high frequency in the mutants containing higher amount of
      11S group I subunit than the wild type, whereas they were hardly observed in the
      mutants lacking 11S group I subunit. These indicate that pro11S group I may
      affect the formation of PBs. Thus, the composition of newly synthesized proteins
      in the ER is important in the selection of the transport pathways.

PMID- 15447651
TI  - Phosphoinositide-specific phospholipase C is involved in cytokinin and gravity
      responses in the moss Physcomitrella patens.
AB  - The phosphoinositide signalling pathway is important in plant responses to
      extracellular and intracellular signals. To elucidate the physiological functions
      of phosphoinositide-specific phopspholipase C, PI-PLC, targeted knockout mutants
      of PpPLC1, a gene encoding a PI-PLC from the moss Physcomitrella patens, were
      generated via homologous recombination. Protonemal filaments of the plc1 lines
      show a dramatic reduction in gametophore formation relative to wild type: this
      was accompanied by a loss of sensitivity to cytokinin. Moreover, plc1 appeared
      paler than the wild type, the result of an altered differentiation of
      chloroplasts and reduced chlorophyll levels compared with wild type filaments. In
      addition, the protonemal filaments of plc1 have a strongly reduced ability to
      grow negatively gravitropically in the dark. These effects imply a significant
      role for PpPLC1 in cytokinin signalling and gravitropism.

PMID- 15447652
TI  - Novel cell wall architecture of isoxaben-habituated Arabidopsis suspension
      cultured cells: global transcript profiling and cellular analysis.
AB  - The herbicide isoxaben is a highly specific and potent inhibitor of cellulose
      synthesis in plants. Nevertheless, suspension-cultured cells can be habituated to
      grow in high concentrations of isoxaben, and apparently compensate for the
      disruption of cellulose synthesis by the modulation of other cell wall
      components. We have habituated Arabidopsis cells to isoxaben and characterized
      the cellular and genetic consequences. Near whole-genome transcript profiling
      implicated novel genes in cell wall assembly and extended our understanding of
      the activity of known cell wall-related genes including glycosyltransferases
      involved in cellulose and pectin biosynthesis. Habituation does not appear to be
      mediated by stress response processes, nor by functional redundancy within the
      cellulose synthase (AtCesA) family. Uniquely, amongst the cellulose synthase
      superfamily, AtCslD5 was highly upregulated and may play a role in the
      biosynthesis of the novel walls of habituated cells. In silico analysis of
      differentially expressed genes with unknown functions identified a putative
      glycosyltransferase and collagen-like putative cell wall protein.

PMID- 15447654
TI  - Formation of an SCF(ZTL) complex is required for proper regulation of circadian
      timing.
AB  - The circadian timing system involves an autoregulatory transcription/translation
      feedback loop that incorporates a diverse array of factors to maintain a 24-h
      periodicity. In Arabidopsis a novel F-box protein, ZEITLUPE (ZTL), plays an
      important role in the control of the free-running period of the circadian clock.
      As a class, F-box proteins are well-established components of the Skp/Cullin/F
      box (SCF) class of E3 ubiquitin ligases that link the target substrates to the
      core ubiquitinating activity of the ligase complex via direct association with
      the Skp protein. Here we identify and characterize the SCFZTL complex in detail.
      Yeast two-hybrid tests demonstrate the sufficiency and necessity of the F-box
      domain for Arabidopsis Skp-like protein (ASK) interactions and the dispensability
      of the unique N-terminal LOV domain in this association. Co-immunoprecipitation
      of full-length (FL) ZTL with the three known core components of SCF complexes
      (ASK1, AtCUL1 and AtRBX1) demonstrates that ZTL can assemble into an SCF complex
      in vivo. F-box-containing truncated versions of ZTL (LOV-F and F-kelch) can
      complex with SCF components in vivo, whereas stably expressed LOV or kelch
      domains alone cannot. Stable expression of F-box-mutated FL ZTL eliminates the
      shortened period caused by mild ZTL overexpression and also abolishes ASK1
      interaction in vivo. Reduced levels of the core SCF component AtRBX1 phenocopy
      the long period phenotype of ztl loss-of-function mutations, demonstrating the
      functional significance of the SCFZTL complex. Taken together, our data establish
      SCFZTL as an essential SCF class E3 ligase controlling circadian period in
      plants.

PMID- 15447655
TI  - Molecular cloning and characterization of norcoclaurine synthase, an enzyme
      catalyzing the first committed step in benzylisoquinoline alkaloid biosynthesis.
AB  - (S)-Norcoclaurine synthase (NCS) (EC 4.2.1.78) catalyzes the condensation of 3,4
      dihydroxyphenylethylamine (dopamine) and 4-hydroxyphenylacetaldehyde (4-HPAA) as
      the first committed step in the biosynthesis of benzylisoquinoline alkaloids such
      as morphine, sanguinarine, and berberine, in plants. A molecular clone encoding
      NCS was isolated from a meadow rue (Thalictrum flavum ssp. glaucum) cell
      suspension culture cDNA library. Heterologous expression of the NCS cDNA,
      truncated to remove a putative signal peptide, produced a recombinant protein
      with NCS activity. Recombinant NCS showed sigmoidal saturation kinetics for
      dopamine (Hill coefficient=1.98), hyperbolic saturation kinetics for 4-HPAA (Km
      of 700 microm), and pH and temperature optima of 7.0 and 40 degrees C,
      respectively, all similar to the purified, plant-derived enzyme. NCS exhibits 28
      38% identity, and putative structural homology, with the Bet v 1 allergen and
      pathogenesis-related (PR)10 protein families. NCS also displays 35% identity with
      the enzyme (HYP1) responsible for hypericin biosynthesis in St John's wort
      (Hypericum perforatum). The novel catalytic functions of NCS and HYP1 define a
      new class of plant secondary metabolic enzymes within the Bet v 1 and PR10
      protein families. Weaker homology was also detected between NCS and proteins
      identified in the latex of Papaver somniferum (opium poppy), and in Arabidopsis
      thaliana. A family of three to five NCS genes is abundantly expressed in the
      rhizome, followed by petioles and roots of T. flavum. NCS transcripts were
      localized to the immature endodermis and pericycle in roots, and the protoderm of
      leaf primordia in rhizomes; thus, the sites of NCS gene expression and berberine
      accumulation are temporally and spatially separated in roots and rhizomes
      respectively.

PMID- 15447656
TI  - Plastid transformation reveals that moss tRNA(Arg)-CCG is not essential for
      plastid function.
AB  - Three distinct arginine tRNA genes, trnR-CCG, trnR-ACG, and trnR-UCU, are present
      in the plastid genome of bryophytes, whereas only the latter two trnR genes are
      present in the major vascular plants, except for black pine. trnR-CCG is located
      between rbcL and accD in the moss Physcomitrella patens and it was previously
      believed to be functional in plastids. However, no trnR-CCG transcript has been
      detected by Northern hybridization, and the codon usage of CGG is quite low in
      plastid protein-coding sequences. This raises the possibility that trnR-CCG is
      non-functional. To investigate this possibility, we integrated a foreign gene
      into the trnR-CCG coding region via homologous recombination, and constructed
      stable plastid trnR-CCG knock-out moss transformants. The trnR-CCG knock-out
      transformants grew normally, indicating that the P. patenstrnR-CCG gene is not
      essential for plastid function.

PMID- 15447657
TI  - Agrodrench: a novel and effective agroinoculation method for virus-induced gene
      silencing in roots and diverse Solanaceous species.
AB  - Summary Virus-induced gene silencing (VIGS) is an extremely powerful tool for
      plant functional genomics. We used Tobacco rattle virus (TRV)-derived VIGS
      vectors expressed from binary vectors within Agrobacterium to induce RNA
      silencing in plants. Leaf infiltration is the most common method of
      agroinoculation used for VIGS but this method has limitations as it is laborious
      for large-scale screening and some plants are difficult to infiltrate. Here we
      have developed a novel and simple method of agroinoculation, called 'agrodrench',
      where soil adjacent to the plant root is drenched with an Agrobacterium
      suspension carrying the TRV-derived VIGS vectors. By agrodrench we successfully
      silenced the expression of phytoene desaturase (PDS), a 20S proteasome subunit
      (PB7) or Mg-protoporphyrin chelatase (Chl H) encoding genes in Nicotiana
      benthamiana and in economically important crops such as tomato, pepper, tobacco,
      potato, and Petunia, all belonging to the Solanaceae family. An important aspect
      of agrodrench is that it can be used for VIGS in very young seedlings, something
      not possible by the leaf infiltration method, which usually requires multiple
      fully expanded leaves for infiltration. We also demonstrated that VIGS functioned
      to silence target genes in plant roots. The agrodrench method of agroinoculation
      was more efficient than the leaf infiltration method for VIGS in roots.
      Agrodrench will facilitate rapid large-scale functional analysis of cDNA
      libraries and can also be applied to plants that are not currently amenable to
      VIGS technology by conventional inoculation methods.

PMID- 15447659
TI  - Mitochondrial uncoupling as a potential therapeutic target in acute central
      nervous system injury.
AB  - Mitochondrial dysfunction, resulting from the disruption of calcium homeostasis
      and the generation of toxic reactive oxygen species, is a central process leading
      to neuronal injury and death following acute CNS insults. Interventions aimed at
      preventing disturbances in mitochondrial function have therefore become targets
      of intense investigation. Mitochondrial uncoupling is a condition in which
      electron transport is disconnected from the production of ATP. As a consequence,
      there is a decrease in the mitochondrial membrane potential, which can
      temporarily decrease calcium influx and attenuate free radical formation. The
      potential use of pharmacological agents with uncoupling properties may provide a
      novel therapeutic approach for the treatment of acute neuronal injury.

PMID- 15447653
TI  - Large-scale analysis of the barley transcriptome based on expressed sequence
      tags.
AB  - To provide resources for barley genomics, 110,981 expressed sequence tags (ESTs)
      were generated from 22 cDNA libraries representing tissues at various
      developmental stages. This EST collection corresponds to approximately one-third
      of the 380,000 publicly available barley ESTs. Clustering and assembly resulted
      in 14,151 tentative consensi (TCs) and 11 073 singletons, altogether representing
      25 224 putatively unique sequences. Of these, 17.5% showed no significant
      similarity to other barley ESTs present in dbEST. More than 41% of all barley
      genes are supposed to belong to multigene families and approximately 4% of the
      barley genes undergo alternative splicing. Based on the functional annotation of
      the set of unique sequences, the functional category 'Energy' was further
      analysed to reveal tissue- and stage-specific differences in gene expression.
      Hierarchical clustering of 362 differentially expressed TCs resulted in the
      identification of seven major clusters. The clusters reflect biochemical pathways
      predominantly activated in specific tissues and at various developmental stages.
      During seed germination glycolysis could be identified as the most predominant
      biochemical pathway. Germination-specific glycolysis is characterized by the
      coordinated expression of phosphoenolpyruvate carboxylase and phosphoenolpyruvate
      carboxykinase, whose antagonistic actions possibly regulate the flux of amino
      acids into protein biosynthesis and gluconeogenesis respectively. The expression
      of defence-related and antioxidant genes during germination might be controlled
      by the ethylene-signalling pathway as concluded from the coordinated expression
      of those genes and the transcription factors (TF) EIN3 and EREBPG. Moreover,
      because of their predominant expression in germinating seeds, TF of the AP2 and
      MYB type are presumably major regulators of germination.

PMID- 15447660
TI  - 1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline-induced apoptosis in the
      human neuroblastoma cell line SK-N-SH.
AB  - Trichloroethylene, a common industrial solvent and a metabolic precursor of
      chloral hydrate, occurs widely in the environment. Chloral hydrate, which is also
      used as a hypnotic, has been found to condense spontaneously with tryptamine, in
      vivo, to give rise to a highly unpolar 1-trichloromethyl-1,2,3,4-tetrahydro-beta
      carboline (TaClo) that has a structural analogy to the dopaminergic neurotoxin N
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Earlier studies have revealed
      the relative permeability of the molecule through the blood-brain barrier and its
      ability to induce Parkinson-like symptoms in rats. In this study, we report that
      TaClo induces an apoptotic pathway in the human neuroblastoma cell line, SK-N-SH,
      involving the translocation of mitochondrial cytochrome c to the cytosol and
      activation of caspase 3. TaClo-induced apoptosis shows considerable differences
      from that mediated by other Parkinson-inducing agents such as MPTP, rotenone and
      manganese. Although it is not clear if the clinically administered dosage of
      chloral hydrate or the relatively high environmental levels of trichloroethylene
      could lead to an onset of Parkinson's disease, the spontaneous in vivo formation
      of TaClo and its pro-apoptotic properties, as shown in this report, should be
      considered.

PMID- 15447661
TI  - Co-transplantation of carotid body and ventral mesencephalic cells as an
      alternative approach towards functional restoration in 6-hydroxydopamine-lesioned
      rats: implications for Parkinson's disease.
AB  - Exogenous administration of various neurotrophic factors has been shown to
      protect neurons in animal model of Parkinson's disease (PD). Several attempts are
      being made to search a tissue source simultaneously expressing many of these
      neurotrophic factors. Carotid body (CB) contains oxygen-sensitive glomus cells
      rich in dopamine (DA) and expresses glial cell line-derived neurotrophic factor,
      brain-derived neurotrophic factor and neurotrophin-3. We have attempted to study
      the functional restoration following co-transplantation of CB cells and ventral
      mesencephalic cells (VMC) in a 6-hydroxydopamine-lesioned rat model of PD. A
      significant recovery (p < 0.001) in d-amphetamine-induced circling behavior (80%)
      and spontaneous locomotor activity (85%) was evident in co-transplanted animals
      at 12 weeks post-transplantation as compared to lesioned animals. Similarly, a
      significant (p < 0.001) restoration was observed in DA-D(2) receptor binding
      (77%), striatal DA (87%) and 3,4-dihydroxyphenylacetic acid (DOPAC) (85%) levels
      and nigral DA (75%) and DOPAC (74%) levels. Functional recovery was accompanied
      by tyrosine hydroxylase (TH) expression and quantification of TH-positive cells
      by image analysis revealed a significant restoration in TH-immunoreactive (IR)
      fiber density in striatum, as well as TH-IR neurons in substantia nigra pars
      compacta in co-transplanted animals over VMC-transplanted animals. The result
      suggests that co-transplantation of CB cells along with VMC provides better and
      long-term functional restoration in the rat model of PD, possibly by supporting
      the survival of newly grafted cells as well as remaining host DA neurons.

PMID- 15447662
TI  - Involvement of cytochrome P450 2E1 in the 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine-induced mouse model of Parkinson's disease.
AB  - Elucidation of the biochemical steps leading to the 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP)-induced degeneration of the nigrostriatal dopamine (DA)
      pathway has provided new clues to the pathophysiology of Parkinson's disease. In
      line with the enhancement of MPTP toxicity by diethyldithiocarbamate (DDC), here
      we demonstrate how other cytochrome P450 (CYP) 2E1 inhibitors, such as diallyl
      sulphide (DAS) and phenylethylisothiocyanate (PIC), also potentiate the selective
      DA neurone degeneration in C57/bl mice. In addition, we show that CYP 2E1 is
      present in the brain and in the basal ganglia of this mouse strain, as measured
      by RT-PCR, western blot analysis and immunohistochemistry. A kinetic analysis of
      MPTP and its metabolites, by means of the microdialysis technique in the
      striatum, indicates that no detoxification metabolic pathway is affected by any
      of these inhibitors. This does not rule out, however, that an undetected
      detoxification pathway involving CYP 2E1 is operating. In order to provide direct
      evidence for this isozyme involvement, CYP 2E1 knockout mice were challenged with
      MPTP or the combined treatment. Here we show that these transgenic mice have a
      low sensitivity to MPTP alone, similar to their wild-type counterparts,
      suggesting that it is likely that transgenic mice compensate for the missing
      enzyme. However, DDC pretreatment completely fails to enhance MPTP toxicity in
      CYP 2E1 knockout mice, whereas this enhancement is regularly present in wild-type
      animals. This study indicates that the occurrence of CYP 2E1 in C57/bl mouse
      brain is relevant to MPTP toxicity, and suggests that this isozyme may have a
      detoxificant role related to the efflux transporter of the toxin.

PMID- 15447663
TI  - U-box protein carboxyl terminus of Hsc70-interacting protein (CHIP) mediates poly
      ubiquitylation preferentially on four-repeat Tau and is involved in
      neurodegeneration of tauopathy.
AB  - Neurofibrillary tangles (NFTs), which are composed of hyperphosphorylated and
      ubiquitylated tau, are exhibited at regions where neuronal loss occurs in
      neurodegenerative diseases; however, the mechanisms of NFT formation remain
      unknown. Molecular studies of frontotemporal dementia with parkinsonism-17
      demonstrated that increasing the ratio of tau with exon 10 insertion induced
      fibrillar tau accumulation. Here, we show that carboxyl terminus of Hsc70
      interacting protein (CHIP), a U-box protein, recognizes the microtubule-binding
      repeat region of tau and preferentially ubiquitylates four-repeat tau compared
      with three-repeat tau. Overexpression of CHIP induced the prompt degradation of
      tau, reduced the formation of detergent-insoluble tau and inhibited proteasome
      inhibitor-induced cell death. NFT bearing neurons in progressive supranuclear
      palsy, in which four-repeat tau is a component, showed the accumulation of CHIP.
      Thus, CHIP is a ubiquitin ligase for four-repeat tau and maintains neuronal
      survival by regulating the quality control of tau in neurons.

PMID- 15447664
TI  - Anatomical substrates for the discriminative stimulus effects of methamphetamine
      in rats.
AB  - Methamphetamine is a psychostimulant drug acting on central monoaminergic neurons
      to produce both acute psychomotor stimulation and long-lasting behavioral effects
      including addiction and psychosis. Drug discrimination procedures have been
      particularly useful in characterizing subjective effects of addictive drugs. In
      the present study, to identify potential anatomical substrates for the
      discriminative stimulus effects of methamphetamine, we investigated the drug
      discrimination-associated Fos expression in Sprague-Dawley rats trained to
      discriminate methamphetamine from saline under a two-lever fixed ratio 20 (FR-20)
      schedule of food reinforcement. The rats that fulfilled the criteria for learning
      the discrimination were anesthetized and perfused 2 h after the drug
      discrimination test, and Fos immunoreactivity was examined in 15 brain regions.
      Fos expression in the brains of rats that discriminate methamphetamine from
      saline was significantly increased in the nucleus accumbens (NAc) and the ventral
      tegmental area (VTA), but not in other areas including the cerebral cortex,
      caudate putamen, substantia nigra, hippocampus, amygdala and habenulla, as
      compared with the expression in control rats that were maintained under the FR-20
      schedule. The present findings suggest a role for the VTA and NAc as possible
      neuronal substrates in the discriminative stimulus effects of methamphetamine.

PMID- 15447665
TI  - Role of serotonin 2A receptors in the D-amphetamine-induced release of dopamine:
      comparison with previous data on alpha1b-adrenergic receptors.
AB  - D-amphetamine is known to induce an increase in dopamine release in subcortical
      structures, thus inducing locomotor hyperactivity in rodents. Previous data have
      indicated that only 15% of the D-amphetamine-induced release of dopamine in the
      nucleus accumbens is related to locomotor activity and that this 'functional'
      dopamine release is controlled by alpha1b-adrenergic receptors located in the
      prefrontal cortex. We show here that SR46349B (0.5 mg/kg, 30 min before D
      amphetamine), a specific serotonin2A (5-HT(2A)) antagonist, can completely block
      0.75 mg/kg D-amphetamine-induced locomotor activity without decreasing D
      amphetamine-induced extracellular dopamine levels in the nucleus accumbens. Using
      the same experimental paradigm as before, i.e. a systemic injection of D
      amphetamine accompanied by a continuous local perfusion of 3 microM D
      amphetamine, we find that SR46349B (0.5 mg/kg) blocks completely the systemic
      (0.75 mg/kg) D-amphetamine-induced functional dopamine release in the nucleus
      accumbens. Finally, the bilateral injection of SR46349B (500 pmol/side) into the
      ventral tegmental area blocked both the D-amphetamine-induced locomotor activity
      and functional dopamine release in the nucleus accumbens, whereas bilateral
      injection of SR46349B into the medial prefrontal cortex was ineffective. We
      propose that 5-HT(2A) and alpha1b-adrenergic receptors control a common neural
      pathway responsible for the release of dopamine in the nucleus accumbens by
      psychostimulants.

PMID- 15447666
TI  - Intraischaemic hypothermia reduces free radical production and protects against
      ischaemic insults in cultured hippocampal slices.
AB  - Hypothermia has been demonstrated to be an effective neuroprotective strategy in
      a number of models of ischaemic and excitotoxic neurodegeneration in vitro and in
      vivo. Reduced glutamate release and free radical production have been postulated
      as potential mechanisms underlying this effect but no definitive mechanism has
      yet been reported. In the current study, we have used oxygen-glucose deprivation
      in organotypic hippocampal slice cultures as an in vitro model of cerebral
      ischaemia. When assessed by propidium iodide fluorescence, reducing the
      temperature during oxygen-glucose deprivation to 31-33 degrees C was
      significantly neuroprotective but this effect was lost if the initiation of
      hypothermia was delayed until the post-insult recovery period. The
      neuroprotective effects of hypothermia were associated with a significant
      decrease in both nitric oxide production, as assessed by 3-amino-4-aminomethyl
      2',7'-difluorofluorescein fluorescence, and superoxide formation. Further,
      hypothermia significantly attenuated NMDA-induced nitric oxide formation in the
      absence of hypoxia/hypoglycaemia. We conclude that the neuroprotective effects of
      hypothermia are mediated through a reduction in nitric oxide and superoxide
      formation and that this effect is likely to be downstream of NMDA receptor
      activation.

PMID- 15447667
TI  - Amphetamine-evoked gene expression in striatopallidal neurons: regulation by
      corticostriatal afferents and the ERK/MAPK signaling cascade.
AB  - The environmental context in which psychostimulant drugs are experienced
      influences their ability to induce immediate early genes (IEGs) in the striatum.
      When given in the home cage amphetamine induces IEGs predominately in
      striatonigral neurons, but when given in a novel test environment amphetamine
      also induces IEGs in striatopallidal neurons. The source of the striatopetal
      projections that regulate the ability of amphetamine to differentially engage
      these two striatofugal circuits has never been described. We report that
      transection of corticostriatal afferents selectively blocks, whereas enhancement
      of cortical activity with an ampakine selectively augments, the number of
      amphetamine-evoked c-fos-positive striatopallidal (but not striatonigral)
      neurons. In addition, blockade of the extracellular signal-regulated kinase
      (ERK)/mitogen-activated protein kinase (MAPK) signaling cascade preferentially
      inhibits the number of amphetamine-evoked c-fos-positive striatopallidal neurons.
      These results suggest that glutamate released from corticostriatal afferents
      modulates the ability of amphetamine to engage striatopallidal neurons through an
      ERK/MAPK signaling-dependent mechanism. We speculate that this may be one
      mechanism by which environmental context facilitates some forms of drug
      experience-dependent plasticity, such as psychomotor sensitization.

PMID- 15447668
TI  - MAPK recruitment by beta-amyloid in organotypic hippocampal slice cultures
      depends on physical state and exposure time.
AB  - Elevated beta-amyloid is thought to trigger the onset of Alzheimer's disease.
      Alzheimer's disease is marked by progressive loss of cognitive function, an early
      symptom of which is episodic memory deficits. Impairment of episodic memory is
      linked to hippocampal pathology. We investigated the signal transduction
      consequences of exposure to nanomolar to low micromolar concentrations of
      aggregate forms of beta-amyloid in the hippocampus. We found that, in addition to
      activation of ERK MAPK and its downstream target ribosomal S6 kinase in
      hippocampal slice cultures following acute exposure to oligomeric beta-amyloid(1
      42), ERK activation also requires phosphoinositide-3 kinase activity. These
      effects were contingent on the alpha7 subtype of nicotinic acetylcholine
      receptor. Hippocampal slice cultures treated acutely with oligomeric beta
      amyloid(1-42) did not exhibit JNK MAPK activation; however, chronic exposure to
      oligomers or high molecular weight aggregates of beta-amyloid(1-42) led to JNK
      MAPK activation coincident with ERK MAPK down-regulation. In contrast to the
      effects of acute application of oligomeric beta-amyloid(1-42), nicotine activated
      ERK MAPK via alpha7 nicotinic acetylcholine receptors utilizing protein kinase A
      as an intermediate. In conclusion, we found that both the physical state and
      duration of exposure to beta-amyloid are determinants of MAPK recruitment in
      hippocampus. We also found that nicotine and beta-amyloid activate ERK MAPK via
      alpha7 nicotinic acetylcholine receptors but use distinct intermediate kinases.
      These data indicate the existence of differential coupling of alpha7 to
      downstream targets depending on the type of ligand that leads to receptor
      activation.

PMID- 15447669
TI  - Dopamine transporter-dependent and -independent actions of trace amine beta
      phenylethylamine.
AB  - Beta-phenylethylamine (beta-PEA) is an endogenous amine that is found in trace
      amounts in the brain. It is believed that the locomotor-stimulating action of
      beta-PEA, much like amphetamine, depends on its ability to increase extracellular
      dopamine (DA) concentrations owing to reversal of the direction of dopamine
      transporter (DAT)-mediated DA transport. beta-PEA can also bind directly to the
      recently identified G protein-coupled receptors, but the physiological
      significance of this interaction is unclear. To assess the mechanism by which
      beta-PEA mediates its effects, we compared the neurochemical and behavioral
      effects of this amine in wild type (WT), heterozygous and 'null' DAT mutant mice.
      In microdialysis studies, beta-PEA, administered either systemically or locally
      via intrastriatal infusion, produced a pronounced outflow of striatal DA in WT
      mice whereas no increase was detected in mice lacking the DAT (DAT-KO mice).
      Similarly, in fast-scan voltammetry studies beta-PEA did not alter DA release and
      clearance rate in striatal slices from DAT-KO mice. In behavioral studies beta
      PEA produced a robust but transient increase in locomotor activity in WT and
      heterozygous mice. In DAT-KO mice, whose locomotor activity and stereotypy are
      increased in a novel environment, beta-PEA (10-100 mg/kg) exerted a potent
      inhibitory action. At high doses, beta-PEA induced stereotypies in WT and
      heterozygous mice; some manifestations of stereotypy were also observed in the
      DAT-KO mice. These data demonstrate that the DAT is required for the striatal DA
      releasing and hyperlocomotor actions of beta-PEA. The inhibitory action on
      hyperactivity and certain stereotypies induced by beta-PEA in DAT-KO mice
      indicate that targets other than the DAT are responsible for these effects.

PMID- 15447670
TI  - Identification of tyrosine hydroxylase as a physiological substrate for Cdk5.
AB  - Cyclin-dependent kinase 5 (Cdk5) is emerging as a neuronal protein kinase
      involved in multiple aspects of neurotransmission in both post- and presynaptic
      compartments. Within the reward/motor circuitry of the basal ganglia, Cdk5
      regulates dopamine neurotransmission via phosphorylation of the postsynaptic
      signal transduction pathway integrator, DARPP-32 (dopamine- and cyclic AMP
      regulated phosphoprotein, M(r) 32,000). Cdk5 has also been implicated in
      regulating various steps in the presynaptic vesicle cycle. Here we report that
      Cdk5 phosphorylates tyrosine hydroxylase (TH), the key enzyme for synthesis of
      dopamine. Using phosphopeptide mapping, site-directed mutagenesis, and
      phosphorylation state-specific antibodies, the site was identified as Ser31, a
      previously defined extracellular signal-regulated kinases 1/2 (ERK1/2) site. The
      phosphorylation of Ser31 by Cdk5 versus ERK1/2 was investigated in intact mouse
      striatal tissue using a pharmacological approach. The results indicated that Cdk5
      phosphorylates TH directly and also regulates ERK1/2-dependent phosphorylation of
      TH through the phosphorylation of mitogen-activated protein kinase kinase 1
      (MEK1). Finally, phospho-Ser31 TH levels were increased in dopaminergic neurons
      of rats trained to chronically self-administer cocaine. These results demonstrate
      direct and indirect regulation of the phosphorylation state of a Cdk5/ERK1/2 site
      on TH and suggest a role for these pathways in the neuroadaptive changes
      associated with chronic cocaine exposure.

PMID- 15447671
TI  - Chagas' disease parasite promotes neuron survival and differentiation through
      TrkA nerve growth factor receptor.
AB  - TrkA is a receptor tyrosine kinase activated primarily by nerve growth factor
      (NGF) to regulate differentiation, survival, and other important functions of
      neurons. Given the critical role TrkA plays in neural maintenance, it may be that
      microbial invaders of the nervous system utilize this receptor to reduce tissue
      damage for maximizing host-parasite equilibrium. Candidate pathogens could be
      those, like Trypanosoma cruzi, which may produce relatively little brain or nerve
      damage in long-lasting infections. We show here that T. cruzi, via its
      neuraminidase, binds TrkA in a NGF-inhibitable manner, induces TrkA
      autophosphorylation, and, through TrkA-dependent mechanisms, triggers
      phosphatidylinositol 3-kinase (PI3K)/Akt kinase signaling, cell survival, and
      neurite outgrowth. Unlike NGF, the neuraminidase does not react with the
      apoptosis-causing pan-neurotrophin receptor p75NTR. Therefore, these studies
      identify a novel and unique TrkA ligand in a microbial invader of the nervous
      system, raising the thus far unsuspected prospect of TrkA underlying clinical
      progression of an important human infectious disease.

PMID- 15447672
TI  - Chimaerins act downstream from neurotrophins in overcoming the inhibition of
      neurite outgrowth produced by myelin-associated glycoprotein.
AB  - Several myelin-derived proteins are inhibitory cues that contribute to the lack
      of regeneration of the CNS and inhibit neurite outgrowth from some neurons in
      vitro. This inhibition is blocked if neurons are exposed to neurotrophins before
      encountering the inhibitors. Here, we demonstrate that chimaerin, one of the Rho
      GTPase activating proteins, is transcriptionally up-regulated after exposure to
      neurotrophins in post-natal cerebellar neurons. The expression of alpha chimaerin
      in the cerebellum is developmentally correlated with the abolishment of the
      inhibitory effect of myelin-associated glycoprotein (MAG). Ectopic expression of
      alpha chimaerin in cerebellar neurons results in resistance to MAG in regard to
      neurite outgrowth. These results suggest that up-regulated expression of
      chimaerin counteracts the activation of RhoA, which is a key molecule in
      transducing inhibitory signals in neurons.

PMID- 15447673
TI  - Induction of cyclooxygenase-2 in reactive glial cells by the CD40 pathway:
      relevance to amyotrophic lateral sclerosis.
AB  - An inflammatory process in association with reactive gliosis has been suggested
      to play an important role in the pathogenesis of amyotrophic lateral sclerosis
      (ALS). One of the key findings is a marked increase in the level of
      cyclooxygenase-2 (COX-2), a therapeutic target of ALS. We investigated the
      expression of CD40 in the spinal cord of a transgenic mouse model of ALS (G93A
      mice), and its relevance to COX-2 upregulation. CD40 was predominantly expressed
      in neurons in normal spinal cord and upregulated in reactive glial cells in
      spinal cord injury. In the spinal cord of G93A mice, the expression of CD40 was
      increased in both reactive microglia and astrocytes, where COX-2 was especially
      increased. The level of COX-2 was upregulated in microglia and astrocytes by CD40
      stimulation in vitro. CD40 stimulation in primary spinal cord cultures caused
      motor neuron loss that was protected by selective COX-2 inhibitor. These results
      suggest that CD40, which is upregulated in reactive glial cells in ALS,
      participates in motor neuron loss via induction of COX-2.

PMID- 15447674
TI  - Cystamine increases L-cysteine levels in Huntington's disease transgenic mouse
      brain and in a PC12 model of polyglutamine aggregation.
AB  - Cystamine, a small disulfide-containing chemical, is neuroprotective in a
      transgenic mouse and a Drosophila model of Huntington's disease (HD) and
      decreases huntingtin aggregates in an in vitro model of HD. The mechanism of
      action of cystamine in these models is widely thought to involve inhibition of
      transglutaminase mediated cross-linking of mutant huntingtin in the process of
      aggregate formation/stabilization. In this study we show that cystamine, both in
      vitro and in a transgenic mouse model of HD (R6/2), increases levels of the
      cellular antioxidant L-cysteine. Several oxidative stress markers increase in HD
      brain. We provide further evidence of oxidative stress in mouse HD by
      demonstrating compensatory responses in R6/2 HD brains. We found age-dependent
      increases in forebrain glutathione (GSH), and increased levels of transcripts
      coding for proteins involved in GSH synthesis and detoxification pathways, as
      revealed by quantitative PCR analysis. Given the general importance of oxidative
      stress as a mediator of neurodegeneration we propose that an increase in brain L
      cysteine levels could be protective in HD. Furthermore, cystamine was
      dramatically protective against 3-nitropropionic acid-induced striatal injury in
      mice. We suggest that cystamine's neuroprotective effect in HD transgenic mice
      results from pleiotropic effects that include transglutaminase inhibition and
      antioxidant activity.

PMID- 15447675
TI  - Gene knockout of amyloid precursor protein and amyloid precursor-like protein-2
      increases cellular copper levels in primary mouse cortical neurons and embryonic
      fibroblasts.
AB  - Alzheimer's disease is characterised by the accumulation of amyloid-beta peptide,
      which is cleaved from the copper-binding amyloid-beta precursor protein. Recent
      in vivo and in vitro studies have illustrated the importance of copper in
      Alzheimer's disease neuropathogenesis and suggested a role for amyloid-beta
      precursor protein and amyloid-beta in copper homeostasis. Amyloid-beta precursor
      protein is a member of a multigene family, including amyloid precursor-like
      proteins-1 and -2. The copper-binding domain is similar among amyloid-beta
      precursor protein family members, suggesting an overall conservation in its
      function or activity. Here, we demonstrate that double knockout of amyloid-beta
      precursor protein and amyloid precursor-like protein-2 expression results in
      significant increases in copper accumulation in mouse primary cortical neurons
      and embryonic fibroblasts. In contrast, over-expression of amyloid-beta precursor
      protein in transgenic mice results in significantly reduced copper levels in
      primary cortical neurons. These findings provide cellular neuronal evidence for
      the role of amyloid-beta precursor protein in copper homeostasis and support the
      existing hypothesis that amyloid-beta precursor protein and amyloid precursor
      like protein-2 are copper-binding proteins with functionally interchangeable
      roles in copper homeostasis.

PMID- 15447676
TI  - Alterations of CaMKII after hypoxia-ischemia during brain development.
AB  - Transient brain hypoxia-ischemia (HI) in neonates leads to delayed neuronal death
      and long-term neurological deficits. However, the underlying mechanisms are
      incompletely understood. Calcium-calmodulin-dependent protein kinase II (CaMKII)
      is one of the most abundant protein kinases in neurons and plays crucial roles in
      synaptic development and plasticity. This study used a neonatal brain HI model to
      investigate whether and how CaMKII was altered after HI and how the changes were
      affected by brain development. Expression of CaMKII was markedly up-regulated
      during brain development. After HI, CaMKII was totally and permanently depleted
      from the cytosol and concomitantly deposited into a Triton-insoluble fraction in
      neurons that were undergoing delayed neuronal death. Autophosphorylation of
      CaMKII-Thr286 transiently increased at 30 min of reperfusion and declined
      thereafter. All these changes were mild in P7 pups but more dramatic in P26 rats,
      consistent with the development-dependent CaMKII expression in neurons. The
      results suggest that long-term CaMKII depletion from the cytosolic fraction and
      deposition into the Triton-insoluble fraction may disable synaptic development,
      damage synaptic plasticity, and contribute to delayed neuronal death and long
      term synaptic deficits after transient HI.

PMID- 15447678
TI  - Overexpression of alpha-synuclein in rat substantia nigra results in loss of
      dopaminergic neurons, phosphorylation of alpha-synuclein and activation of
      caspase-9: resemblance to pathogenetic changes in Parkinson's disease.
AB  - To elucidate the role of alpha-synuclein in the pathogenesis of Parkinson's
      disease, both human alpha-synuclein transgenic mice and targeted overexpression
      of human alpha-synuclein in rat substantia nigra using viral vector-based methods
      have been studied, however, little is known about the pathogenetic changes of
      dopaminergic neuron loss. Therefore, it is necessary to address whether the
      pathogenetic changes in brains with Parkinson's disease are recapitulated in
      these models. Here, we used the recombinant adeno-associated viral (rAAV) vector
      system for human alpha-synuclein gene transfer to rat substantia nigra and
      observed approximately 50% loss of dopaminergic neurons at 13 weeks after
      infection, which was comparably slower than the progression of neurodegeneration
      reported in other studies. In the slower progression of neurodegeneration, we
      identified several important features in common with the pathogenesis of
      Parkinson's disease, such as phosphorylation of alpha-synuclein at Ser129 and
      activation of caspase-9. Both findings were also evident in cortical tissues
      overexpressing alpha-synuclein via rAAV. Our results indicate that overexpression
      of alpha-synuclein via rAAV apparently recapitulates several important features
      of brains with Parkinson's disease and dementia with Lewy bodies, and thus alpha
      synucleinopathy described here is likely to be an ideal model for the study of
      the pathogenesis of Parkinson's disease and dementia with Lewy bodies.

PMID- 15447679
TI  - NMDA receptor activation results in PKA- and ERK-dependent Mnk1 activation and
      increased eIF4E phosphorylation in hippocampal area CA1.
AB  - Protein synthesis is essential for the stabilization of glutamate receptor
      dependent forms of long-lasting hippocampal synaptic plasticity and for the
      consolidation of memory, but the signal transduction mechanisms that regulate
      translation factors during these processes are not well understood. As a first
      step towards understanding how translation is activated during synaptic
      plasticity, we investigated how the eukaryotic initiation factor 4E (eIF4E), a
      rate-limiting mRNA cap-binding protein, and its kinase, Mnk1, are regulated by
      protein kinase C (PKC), cAMP-dependent protein kinase (PKA) and N-methyl-D
      aspartate (NMDA) receptor activation in hippocampal area CA1. We found that
      treatment of mouse hippocampal slices with either phorbol ester, to activate PKC,
      or forskolin, to activate PKA, resulted in activation of Mnk1 and increased eIF4E
      phosphorylation that was dependent on extracellular signal-regulated kinase
      (ERK). Similarly, brief treatment of hippocampal slices with NMDA resulted in
      activation of Mnk1 and increased phosphorylation of eIF4E. The NMDA-induced
      activation of Mnk1 and increased phosphorylation of eIF4E were dependent on PKA
      and ERK, but not PKC, and were present in synaptoneurosome preparations.
      Immunohistochemical analysis revealed that the PKA- and ERK-dependent increases
      in Mnk1 activation induced by NMDA also occurred in dendrites. These findings
      identify a specific regulatory pathway that can couple NMDA receptor activation
      to translation initiation factors in the hippocampus, and may represent a
      mechanism for triggering dendritic protein synthesis during long-term
      potentiation and long-term memory formation.

PMID- 15447677
TI  - Proteomic analysis of native metabotropic glutamate receptor 5 protein complexes
      reveals novel molecular constituents.
AB  - We used a proteomic approach to identify novel proteins that may regulate
      metabotropic glutamate receptor 5 (mGluR5) responses by direct or indirect
      protein interactions. This approach does not rely on the heterologous expression
      of proteins and offers the advantage of identifying protein interactions in a
      native environment. The mGluR5 protein was immunoprecipitated from rat brain
      lysates; co-immunoprecipitating proteins were analyzed by mass spectrometry and
      identified peptides were matched to protein databases to determine the
      correlating parent proteins. This proteomic approach revealed the interaction of
      mGluR5 with known regulatory proteins, as well as novel proteins that reflect
      previously unidentified molecular constituents of the mGluR5-signaling complex.
      Immunoblot analysis confirmed the interaction of high confidence proteins, such
      as phosphofurin acidic cluster sorting protein 1, microtubule-associated protein
      2a and dynamin 1, as mGluR5-interacting proteins. These studies show that a
      proteomic approach can be used to identify candidate interacting proteins. This
      approach may be particularly useful for neurobiology applications where distinct
      protein interactions within a signaling complex can dramatically alter the
      outcome of the response to neurotransmitter release, or the disruption of normal
      protein interactions can lead to severe neurological and psychiatric disorders.

PMID- 15447680
TI  - Inhibition of glutamate-induced delayed calcium deregulation by 2-APB and La3+ in
      cultured cortical neurones.
AB  - Exposure of neurones in culture to excitotoxic levels of glutamate results in an
      initial transient spike in [Ca2+]i followed by a delayed, irreversible [Ca2+]i
      rise governed by rapid kinetics, with Ca2+ originating from the extracellular
      medium. The molecular mechanism responsible for the secondary Ca2+ rise is
      unknown. Here, we report that the delayed Ca2+ entry in cortical neurones is
      diminished by 2-aminoethoxydiphenyl borate (2-APB: IC50 = 62 +/- 9 microm) and
      La3+ (IC50 = 7.2 +/- 3 microm), both known to inhibit transient receptor
      potential (TRP) and store-operated Ca2+ (SOC) channels. Application of
      thapsigargin, however, failed to exacerbate the delayed Ca2+ deregulation,
      arguing against a store depletion event as the stimulus for induction of the
      secondary [Ca2+]i rise. In addition, these neurones did not exhibit SOC entry.
      Unexpectedly, application of ryanodine or caffeine significantly inhibited
      glutamate-induced delayed Ca2+ deregulation. In basal Ca2+ entry experiments,
      La3+ and 2-APB modulated the rapid rise in [Ca2+]i caused by exposure of neurones
      to Ca2+ after pre-incubating in a calcium-free medium. This basal Ca2+ influx was
      mitigated by extracellular Mg2+ but not aggravated by thapsigargin, ryanodine or
      caffeine. These results indicate that 2-APB and La3+ influence non-store-operated
      Ca2+ influx in cortical neurones and that this route of Ca2+ entry is involved in
      glutamate-induced delayed Ca2+ deregulation.

PMID- 15447681
TI  - A novel constitutively active mutation in the second cytoplasmic loop of
      metabotropic glutamate receptor.
AB  - G protein-coupled receptors have a common structural motif of seven transmembrane
      alpha-helices and are classified into different families showing no sequence
      similarity. Extensive studies have been conducted on the structure-function
      relationship in family 1 receptors, but those in other families have not been
      well studied. In this study, to investigate the molecular basis leading to the G
      protein activation by metabotropic glutamate receptor (mGluR), the member of
      family 3, we searched for the amino acid residues responsible for the G protein
      activation in the second cytoplasmic loop, which was thought to be the main G
      protein binding region. Analyses of the systematical mutations of Gi/Go-coupled
      mGluR8 revealed the presence of a constitutively active mutation in the C
      terminal region of the second loop. The corresponding mutation in the second loop
      of Gq-coupled mGluR1 also exhibited high agonist-independent activity. These
      results indicate that there is a common constitutive active mutation site
      regardless of mGluR subtypes, suggesting that the structural change of the
      junction between the second cytoplasmic loop and helix IV is strongly linked to
      the formation of the active state.

PMID- 15447682
TI  - Evidence for histamine as a transmitter in rat carotid body sensor cells.
AB  - Carotid bodies harboring sensor cells for oxygen have a strategic location at the
      bifurcation of the carotid artery, which supplies the brain. Upon arterial
      hypoxia they transmit signals to the respiratory center, which increases the
      frequency of breathing. Dopamine is considered as the predominant transmitter of
      the rat carotid body sensor cells. Here we show that the rat carotid body sensor
      cells are the first cell type known to have the complete apparatus to synthesize,
      store and release both dopamine and histamine. The tyrosine hydroxylase positive
      dopaminergic sensor cells of juvenile rats express the histamine biosynthesis
      enzyme, histidine decarboxylase. Moreover, the sensor cells have not only
      vesicular monoamine transporter 1 (VMAT1) transporting catecholamines but also
      VMAT2, which is highly specific for histamine. Additionally, we found that these
      cells possess components of the neuroendocrine exocytosis apparatus, synaptosome
      associated protein of 25 kDa (SNAP 25) and syntaxin1. The amount of histamine
      determined in the rat carotid body (164 pmol/carotid body) is more than 10-fold
      higher compared with that of dopamine. As a main effect, hypoxia significantly
      increased histamine release from isolated rat carotid bodies as it has been shown
      for dopamine. Finally, RT-PCR experiments indicate the presence of histamine
      receptors H1, H2 and H3 in the carotid body. Our data suggest that histamine is
      synthesized, stored and released upon hypoxia by dopaminergic sensor cells of the
      rat carotid body.

PMID- 15447683
TI  - Rho-mediated cytoskeletal rearrangement in response to LPA is functionally
      antagonized by Rac1 and PIP2.
AB  - G-protein-coupled receptors signal through Rho to induce actin cytoskeletal
      rearrangement. We previously demonstrated that thrombin stimulates Rho-dependent
      process retraction and rounding of 1321N1 astrocytoma cells. Surprisingly, while
      lysophosphatidic acid (LPA) activated RhoA in 1321N1 cells, it failed to produce
      cell rounding. Thrombin, unlike LPA, decreased Rac1 activity, and activated
      (GTPase-deficient) Rac1 inhibited thrombin-stimulated cell rounding, while
      expression of dominant-negative Rac1 promoted LPA-induced rounding. LPA and
      thrombin receptors appear to differ in coupling to Gi, as LPA but not thrombin
      stimulated 1321N1 cell proliferation was pertussis toxin-sensitive. Blocking Gi
      with pertussis toxin enabled LPA to induce cell rounding and to decrease
      activated Rac1. These data support the hypothesis that Rac1 and Gi activation
      antagonize cell rounding. Thrombin and LPA receptors also differentially
      activated Gq pathways as thrombin but not LPA increased InsP3 formation and
      reduced phosphatidylinositol 4,5-bisphosphate (PIP2) levels. Microinjection of
      the plekstrin homology domain of phospholipase C (PLC)delta1, which binds PIP2,
      enabled LPA to elicit cell rounding, consistent with a requirement for PIP2
      reduction. We suggest that Rho-mediated cytoskeletal responses are enhanced by
      concomitant reductions in cellular levels of PIP2 and Rac1 activation and thus
      effected only by G-protein-coupled receptors with appropriate subsets of G
      protein activation.

PMID- 15447684
TI  - Cytochemical and ultrastructural characterization of growing colonies of human
      embryonic stem cells.
AB  - The morphology of human embryonic stem (ES) cells changes with their colonial
      growth. For a better understanding of the growth of ES cell colonies in culture,
      we determined their cytochemical and ultrastructural characteristics focusing on
      images of living cells under a phase contrast microscope. During the initial
      growth stages, the colonies exhibited a mosaic appearance with discernible cell
      cell borders. PAS staining coupled with amylase digestion demonstrated that the
      bright granules and dark deposits in the cytoplasm contained glycogen.
      Ultrastructurally they were glycogen accumulations, and clustered open spaces
      associated with various amounts of glycogen. Although intercellularly
      heterogeneous, these structures were detectable throughout colony growth. As the
      colonies grew, compaction towards the centre emerged and increased, accompanied
      by heterogeneous increases in coarse particles with or without a halo. TUNEL
      showed these particles to consist at least in part of apoptotic cells/bodies.
      Transmission electron microscopy indicated that most apoptotic cells had been
      phagocytosed by intact ES cells. Spontaneous differentiation was detected
      occasionally in the periphery of the colonies. The presence of PAS-positive
      fibrous structures not susceptible to amylase digestion and laminin
      immunoreactivity indicated the accumulation of extracellular matrix in the
      peripheral differentiated areas. These findings made it possible to determine the
      growth stage of human ES cell colonies.

PMID- 15447685
TI  - Tissue-specific expression of the tight junction proteins claudins and occludin
      in the rat salivary glands.
AB  - Tight junctions (TJs) are essential features of endothelial barrier membranes and
      of fluid-secreting epithelial cells, such as in the salivary glands. Novel
      integral membrane proteins have been identified as components of TJs, namely
      claudins and occludin. The aim of the present study was to determine the
      distribution of occludin and claudins in the large salivary glands of the rat.
      The parotid, submandibular and sublingual salivary glands were harvested from
      adult Sprague-Dawley rats and cryostat sections were stained using
      immunoperoxidase and immunofluorescence methods. Claudin-1 was expressed in
      endothelial cells of microvessels and in short selected segments of the duct
      system. Claudin-3 was expressed principally in the acinar cells and intercalated
      ducts, while claudin-4 was principally expressed by the striated and interlobular
      ducts. Claudin-5 was specific to endothelial cells of microvessels. Occludin was
      ubiquitously detected in the duct system. Double labelling and confocal
      microscopy showed some co-localization of claudin-3 with claudin-4, and minimal
      co-localization of occludin with claudin-4, in the striated ducts. Claudin 2 was
      not detected in any of the salivary glands. The results indicate specificity of
      the chemical composition of tight junctions in the rat salivary glands, and may
      reflect different physiological roles for TJs in the glandular and duct
      epithelial cells, and in endothelial cells of salivary gland microvessels.

PMID- 15447686
TI  - A stereological evaluation of secretin and gastric inhibitory peptide-containing
      mucosal cells of the perinatal small intestine of the pig.
AB  - Stereological methods were used to quantify secretin and gastric inhibitory
      peptide (GIP)-immunoreactivity (GIP-IR) in paraffin sections of the duodenum,
      jejunum and ileum of fetal and neonatal piglets. In addition, sections were
      processed for GLP-1-immunohistochemistry. The volume density of the tunica mucosa
      increased after birth, giving rise to a decreased volume density of the tela
      submucosa and tunica muscularis. Generally known region-specific morphological
      distinctions were reflected in differing volume densities of the various layers.
      The highest volume density of GIP-IR epithelial cells was observed in the jejunum
      of the neonate. In contrast, the volume density of secretin-IR epithelial cells
      was highest in the duodenum of both fetal and neonatal piglets. The volume
      occupied by GIP-IR and secretin-IR epithelial cells increased in the jejunum
      after birth. Additionally, ileal secretin-IR epithelial cells were more numerous
      in the neonatal piglet. In conclusion, the quantitative and qualitative presence
      of GIP-IR and secretin-IR epithelial cells agree with earlier reports of their
      presence and co-localization between GIP-IR and GLP-1-IR, in the pig small
      intestine. Furthermore, the differences suggest that age- and region-related
      functional demands are temporally and probably causally related with the
      morphological diversification of the intestine and its endocrine cells.

PMID- 15447687
TI  - Morphometric and immunohistochemical study of the reticulum of red deer during
      prenatal development.
AB  - Iberian red deer need to be conserved for their economic role and for their
      genetic importance as an important component of the ecosystem. Modifications
      currently being made to traditional management systems require a better
      understanding of the structure, function and development of their alimentary
      system. Here we describe a histomorphometric and immunohistochemical analysis of
      the stomach of 25 red deer embryos and fetuses from 30 days of gestation until
      birth (235 days). Differentiation of the reticular compartment from the primitive
      gastric tube begins at 67 days, forming a three-layered structure: epithelium,
      pluripotential blastemal tissue and serosa. The primitive reticular cells are
      initiated as small epithelial evaginations (primary ribs) at 117 days. At 142
      days, lateral growths appear from the primary reticular ribs, forming the corneum
      papillae. The secondary reticular ribs form at 142 days as growths from the
      primary ribs. The uneven height of primary and secondary reticular ribs leads to
      the formation of cells of varying size. Growth of the reticular ribs involves the
      lamina propria but not the submucosa, so clear separation of these layers is
      maintained during histodifferentiation. Formation of the tunica muscularis from
      the pluripotential blastemal tissue begins at 67 days of intrauterine life, as
      two layers of longitudinally and circularly arranged myoblasts. Differentiation
      of the muscularis from the mucosa occurs at approximately 205 days, as
      longitudinal projections of the internal bundles of the tunica muscularis form
      the musculature of the primary ribs. The secretion of neutral and acid
      mucopolysaccharides by the reticular epithelial layer begins at 67 days,
      establishing the gradual adaptation of the mucosa to its protective function in
      postnatal life. Neuroendocrine (non-neuron enolase) and glial cells (glial
      fibrillary acidic protein and vimentin) were detected by immunohistochemistry, in
      a similar localization and intensity to that reported in the rumen. The
      neuropeptides vasoactive intestinal peptide and neuropeptide Y showed a positive
      immunoreaction in the reticular epithelium from 142 days of prenatal life, again
      earlier than reported for the rumen. In comparison with domestic ruminants, deer
      were shown to be less precocious with regard to development of gastric tube, in
      their capacity to secrete neutral mucopolysaccharides, and in their
      neuroendocrine nature, as determined by the detection of positive neuroendocrine
      and/or glial cells.

PMID- 15447688
TI  - In vivo leptin expression in cartilage and bone cells of growing rats and adult
      humans.
AB  - The present investigation was carried out to analyse, immunohistochemically, in
      vivo leptin expression in cartilage and bone cells, the latter restricted to the
      elements of the osteogenic system (stromal cells, osteoblasts, osteocytes, bone
      lining cells). Observations were performed on the first lumbar vertebra, tibia
      and femur of four rats and on the humerus, femur and acromion of four patients.
      Histological sections of paraffin-embedded bone samples were immunostained using
      antibody to leptin. The results showed that, in growing rat bone, leptin is
      expressed in chondrocytes and stromal cells, but not in osteoblasts; bone lining
      cells were not found in the microscopic fields examined. In adult human bone,
      leptin is expressed in chondrocytes, stromal cells and bone lining cells;
      osteoblasts were not found in the microscopic fields examined. Osteocytes were
      found to be leptin positive only occasionally and focally in both rat and human
      bone. The in vivo findings reported show, for the first time, that leptin appears
      to be expressed only in the cells of the osteogenic lineage (stromal cells, bone
      lining cells, osteocytes) that, with respect to osteoblasts, are permanent and
      inactive, i.e. in those cells that according to our terminology constitute the
      bone basic cellular system (BBCS). Because the BBCS seems to be primarily
      involved in sensing and integrating mechanical strains and biochemical factors
      and then in triggering and driving bone formation and/or bone resorption, it
      appears that leptin seems to be mainly involved in modulating the initial phases
      of bone modelling and remodelling processes.

PMID- 15447689
TI  - A mesenchyme-free culture system to elucidate the mechanism of otic vesicle
      morphogenesis.
AB  - The vertebrate inner ear has been extensively studied as a model system of
      morphogenesis and differentiation. The interactions between epithelium and
      surrounding mesenchyme have not previously been studied directly, because an
      appropriate experimental system had not been established. Here we describe a
      mesenchyme-free culture system of E11.5 mouse otic vesicle which retains the
      ability for (1) formation of the cochlear loop, (2) emigration of ganglion cells
      from the epithelium and (3) invagination of semicircular canal epithelium. E10.5
      otic vesicle was maintained using the same method, but morphogenesis was less
      successful. Culture of the E11.5 cochlear region alone resulted in regeneration
      of a structure with semicircular canal character from the cut end, indicating
      that region-specific cell fate within the otic vesicle is not irreversibly
      determined at this stage. Co-culturing otic vesicle with cochleovestibular
      ganglion (CVG) resulted in enhanced looping or ectopic diverticulum formation of
      the cochlear region, suggesting that the CVG provides a morphogenetic signal for
      cochlear looping. Cochlear looping was specifically blocked by inhibiting actin
      polymerization by cytochalasin D, while morphogenesis of the semicircular canal
      region remained intact. Hyaluronidase treatment inhibited semicircular canal
      morphogenesis, resulting in a cystic form of the otic vesicle. These data
      validate this culture system as a tool for elucidating the mechanism of
      morphogenesis of the otic vesicle.

PMID- 15447690
TI  - No change in neuron numbers in the dentate nucleus of patients with schizophrenia
      estimated with a new stereological method--the smooth fractionator.
AB  - The dentate nucleus is phylogenetically the most recent nucleus in the
      cerebellum. Owing to its connections to the thalamus and the prefrontal cortex it
      may be involved in the symptomathology in schizophrenia and other psychiatric
      illnesses. In this stereological study we implemented the smooth fractionator,
      which combines the unbiased principles of the optical fractionator with a new and
      more efficient sampling strategy to the dentate nucleus. The smooth fractionator
      represents the most efficient sampling strategy described so far in stereology,
      in terms of reducing the sampling variance and thus increasing the efficiency. It
      is the first application of the smooth fractionator to human brain tissue and
      presents estimations of total number of neurons in the dentate nuclei of eight
      patients with schizophrenia compared to eight control persons. The total number
      of neurons in the dentate nucleus was estimated to 3.36 x 10(6) in subjects with
      schizophrenia, which was not statistically significant different from 3.65 x
      10(6) in control subjects (P = 0.63). The advantages and disadvantages of the
      smooth fractionator method are discussed and its precision in practical
      application is estimated.

PMID- 15447691
TI  - Interobserver error involved in independent attempts to measure cusp base areas
      of Pan M1s.
AB  - Cusp base areas measured from digitized images increase the amount of detailed
      quantitative information one can collect from post-canine crown morphology.
      Although this method is gaining wide usage for taxonomic analyses of extant and
      extinct hominoids, the techniques for digitizing images and taking measurements
      differ between researchers. The aim of this study was to investigate
      interobserver error in order to help assess the reliability of cusp base area
      measurement within extant and extinct hominoid taxa. Two of the authors measured
      individual cusp base areas and total cusp base area of 23 maxillary first molars
      (M(1)) of Pan. From these, relative cusp base areas were calculated. No
      statistically significant interobserver differences were found for either
      absolute or relative cusp base areas. On average the hypocone and paracone showed
      the least interobserver error (< 1%) whereas the protocone and metacone showed
      the most (2.6-4.5%). We suggest that the larger measurement error in the
      metacone/protocone is due primarily to either weakly defined fissure patterns
      and/or the presence of accessory occlusal features. Overall, levels of
      interobserver error are similar to those found for intraobserver error. The
      results of our study suggest that if certain prescribed standards are employed
      then cusp and crown base areas measured by different individuals can be pooled
      into a single database.

PMID- 15447694
TI  - Prevalence and diagnosis of migraine in patients consulting their physician with
      a complaint of headache: data from the Landmark Study.
AB  - CONTEXT: Headache experts have suggested that to improve the recognition of
      migraine, patients with a stable pattern of episodic, disabling headache and a
      normal physical exam should be considered to have migraine in the absence of
      contradictory evidence. The premise upon which this approach is based-that is,
      that episodic, recurrent primary headache in the clinic is usually migraine-has
      not been evaluated in prospective clinical studies. OBJECTIVES: To (1) evaluate
      the diagnoses of patients consulting their physician with primary episodic
      headache and (2) compare clinic diagnoses and patient self-diagnoses with
      International Headache Society (IHS) headache diagnoses assigned on the basis of
      longitudinal data from patient diaries. DESIGN: Prospective, open-label study.
      During the screening visit, patients self-reported a headache diagnosis and then
      were assigned a headache diagnosis by their physician following his or her
      customary practice. Patients with a new physician diagnosis of migraine or
      nonmigraine primary headache were given diaries to record headache symptoms for
      up to 3 months or 6 attacks. Members of an expert panel, unaware of the clinic
      diagnosis, used diary data to assign a headache diagnosis to each attack and to
      each patient. SETTING: One hundred twenty-eight (128) practices in 15 countries
      including the United States. PATIENTS: A total of 1203 male and female patients
      between 18 and 65 years of age who consulted their physician with headache as a
      primary or secondary complaint. RESULTS: Overall, 94% of patients with a
      physician diagnosis of nonmigraine primary headache or a new clinic diagnosis of
      migraine had IHS-defined migraine (76%) or probable migraine (migrainous) (18%)
      headache on the basis of longitudinal diary data. A new clinic diagnosis of
      migraine was almost always correct: 98% of patients with a clinic diagnosis of
      migraine had IHS-defined migraine (87% of patients) or probable migraine (11% of
      patients) headache on the basis of longitudinal diary data. On the other hand,
      review of diaries of patients with a clinic diagnosis of nonmigraine revealed
      that 82% of these patients had IHS-defined migraine (48%) or probable migraine
      (34%) headache. Altogether, one in four patients (25%) with IHS-defined migraine
      according to longitudinal diary data did not receive a clinic diagnosis of
      migraine. CONCLUSIONS: These findings support the diagnostic approach of
      considering episodic, disabling primary headaches with an otherwise normal
      physical exam to be migraine in the absence of contradictory evidence. If in
      doubt of diagnosis or when assigning a nonmigraine diagnosis, strong
      consideration should be given to the use of a diary to confirm primary headache
      diagnosis.

PMID- 15447695
TI  - The premonitory symptoms (prodrome): a tertiary care study of 893 migraineurs.
AB  - OBJECTIVES: This study of premonitory symptoms in migraine was performed to
      document the frequency, duration, and types of symptoms in a large group of
      migraine patients. BACKGROUND: Prodrome importance continues to be debated.
      Intervention early in the migraine attack is assuming more importance and
      necessitates better knowledge of the prodrome. METHODS: A total of 893 migraine
      patients (IHS 1.1-1.7) were evaluated at first visit. Prodrome frequency,
      duration, and characteristics were analyzed in the total migraine population IHS
      1.1-1.7 and IHS 1.1-1.6 migraine. RESULTS: A total of 32.9% of IHS migraine 1.1
      1.6 patients reported prodrome symptoms with an average of 9.42 hours. IHS 1.1
      1.7 migraine reported 29.7% and 6.8 hours, respectively. The most commonest
      symptoms were tiredness, mood change, and gastrointestinal symptoms; all three of
      these symptoms were present together in 17% of the patients with prodrome. The
      duration of prodrome was less than 1 hour in 45.1%, 1-2 hours in 13.6%, 2-4 hours
      in 15.0%, 4-12 hours in 13.1%, and greater than 12 hours in 13.2%. IHS 1.1-1.7
      patients showed similar findings. IHS 1.1-1.6 patients with prodrome differed
      from patients without prodrome in having more triggers as a whole (P <.01), more
      individual triggers including alcohol (P <.01), hormones (P <.01), light (P
      <.001), not eating (P <.05), perfume (P <.01), stress (P <.01), and weather
      changes (P <.05), a longer duration of aura (P <.05), longer time between aura
      and headache (P <.05), more aura with no headache (P <.05), longer time to peak
      of headache (P <.05), longer time to respond to triptan (P <.05), longer maximum
      duration of headache (P <.05), and more headache associated nausea (P <.05), more
      headache associated running of the nose or tearing of the eyes (P <.05), more
      postdrome syndrome (P <.05), and longer duration of postdrome syndrome (P <.001).
      CONCLUSIONS: This study provides a portrait of prodrome in a large cohort of
      patients. It highlights differences between patients with prodrome and patients
      not having prodrome, and it draws attention to the potential of preventing the
      headache phase of the acute migraine attack.

PMID- 15447696
TI  - Quantifying headache symptoms and other headache features from chart notes.
AB  - OBJECTIVES: To describe a method for quantifying headache symptoms/features in
      family practice charts for patients diagnosed with headache NOS (not otherwise
      specified, ICD-9: 784) and to determine the share of NOS headache diagnoses with
      clinical data strongly suggestive of migraine or probable migraine headache.
      BACKGROUND: Headache is one of the most common pain symptoms that brings patients
      to a family physician. However, the majority of headache sufferers do not receive
      a specific headache diagnosis when they visit physicians. METHODS: We examined
      the chart notes of 454 patients exclusively diagnosed with one or more ICD-9
      coded headache NOS diagnoses from July 1, 1995 through December 31, 1999 at a
      large suburban, university-affiliated practice. We developed a template
      containing 20 headache items combining International Headache Society diagnostic
      criteria and additional headache symptoms/features, and decision rules for coding
      symptoms/features and collected data from patient charts. We then developed
      decision rules and reclassified NOS headaches into categories strongly suggestive
      of migraine, probable migraine headache, or other diagnosis. Our main outcome
      measure is the consistency in the application of decision rules and diagnostic
      criteria. RESULTS: With this method we estimate 3 in 10 (29%) headache NOS
      patients may have had migraine (8%) or probable migraine headache (21%).
      Reclassified migraine visits averaged 6.5 migraine symptoms and reclassified
      probable migraine headache visits 4.7 migraine symptoms. Logistic regression
      analysis supports the consistency of diagnostic criteria for classifying headache
      based on coded symptoms/features--our model correctly predicted 96% of visits.
      Evidence of physical examination was recorded at 75% of visits suggesting that
      physician attention is focused on elimination of secondary headache. CONCLUSIONS:
      We think the use of our rigorous procedures reveals that a substantial amount of
      migraine and probable migraine headache may be missed in everyday practice. We
      hope our findings will provide a basis for the development of diagnostic methods
      more closely suited to the needs of nonspecialists, and contribute to a better
      standard of care for headache patients seen in primary care practice. Finally, we
      are hopeful that other researchers will consider using our template and guideline
      procedures in their efforts to identify diagnostic patterns and study headache
      and other health problems.

PMID- 15447697
TI  - A combination of riboflavin, magnesium, and feverfew for migraine prophylaxis: a
      randomized trial.
AB  - OBJECTIVE: To determine the efficacy for migraine prophylaxis of a compound
      containing a combination of riboflavin, magnesium, and feverfew. BACKGROUND:
      Previous studies of magnesium and feverfew for migraine prophylaxis have found
      conflicting results, and there has been only a single placebo-controlled trial of
      riboflavin. DESIGN/METHODS: Randomized double-blind placebo-controlled trial of a
      compound providing a daily dose of riboflavin 400 mg, magnesium 300 mg, and
      feverfew 100 mg. The placebo contained 25 mg riboflavin. The study included a 1
      month run-in phase and 3-month trial. The protocol allowed for 120 patients to be
      randomized, with a preplanned interim analysis of the data after 48 patients had
      completed the trial. RESULTS: Forty-nine patients completed the 3-month trial.
      For the primary outcome measure, a 50% or greater reduction in migraines, there
      was no difference between active and "placebo" groups, achieved by 10 (42%) and
      11 (44%), respectively (P=.87). Similarly, there was no significant difference in
      secondary outcome measures, for active versus placebo groups, respectively: 50%
      or greater reduction in migraine days (33% and 40%, P=.63); or change in mean
      number of migraines, migraine days, migraine index, or triptan doses. Compared to
      baseline, however, both groups showed a significant reduction in number of
      migraines, migraine days, and migraine index. This effect exceeds that reported
      for placebo agents in previous migraine trials. CONCLUSION: Riboflavin 25 mg
      showed an effect comparable to a combination of riboflavin 400 mg, magnesium 300
      mg, and feverfew 100 mg. The placebo response exceeds that reported for any other
      placebo in trials of migraine prophylaxis, and suggests that riboflavin 25 mg may
      be an active comparator. There is at present conflicting scientific evidence with
      regard to the efficacy of these compounds for migraine prophylaxis.

PMID- 15447698
TI  - Rizatriptan 5 mg for the acute treatment of migraine in adolescents: results from
      a double-blind, single-attack study and two open-label, multiple-attack studies.
AB  - OBJECTIVE: To examine the short- and long-term efficacy and tolerability of
      rizatriptan 5 mg in adolescents with migraine. METHODS: Two studies were
      conducted in patients aged 12 to 17 years. The first study was a randomized,
      double-blind, placebo-controlled, single-attack study followed by a randomized, 1
      year, open-label extension. The second study was a randomized, 1-year, open-label
      study. In the single-attack study, patients treated a moderate or severe migraine
      headache and up to two recurrences with rizatriptan 5-mg tablets (n = 234) or
      placebo (n = 242). Patients were instructed to use the study medication only on
      nonschool days. Headache severity, associated symptoms, and functional disability
      were assessed by the patient at 0.5, 1, 1.5, 2, 3, and 4 hours after the initial
      dose. In the 1-year studies, patients treated up to 6 migraine attacks per month
      with rizatriptan 5-mg tablets (n = 273), rizatriptan 5-mg wafers (n = 281), or
      standard care therapy (n = 132). Headache severity was assessed by the patient at
      2 hours after the initial dose. In all studies, the primary efficacy measure was
      pain relief at 2 hours post dose. RESULTS: In the single-attack study, the
      proportion of patients with pain relief at 2 hours was not significantly
      different between rizatriptan 5 mg (68.2%) and placebo (68.8%). Fewer patients
      than expected (about 30%) treated their migraine attacks on the weekend. Among
      these patients, the proportion with pain relief at 2 hours was significantly
      higher in the rizatriptan group than in the placebo group (74% vs. 58%, P =
      0.022). In the multiple-attack studies, pain relief at 2 hours was achieved in
      significantly more attacks treated with rizatriptan 5-mg tablet (77%) or with
      rizatriptan 5-mg wafer (77%) than with standard care (64%). Rizatriptan 5 mg was
      well tolerated in both the studies, with an adverse event profile not
      significantly different from that of placebo or standard care. CONCLUSIONS:
      Rizatriptan 5 mg was not more effective than placebo in the treatment of a single
      migraine attack in adolescents, but appeared to be more effective than standard
      care for treating multiple attacks occurring over 1 year in these patients.
      Rizatriptan 5 mg was well tolerated in adolescents during short-term and long
      term use.

PMID- 15447699
TI  - Migraine treatment with rizatriptan and non-triptan usual care medications: a
      pharmacy-based study.
AB  - OBJECTIVE: To compare the effectiveness of rizatriptan to other non-triptan
      medications in the relief of migraine headache in usual care settings.
      BACKGROUND: Although rizatriptan has been shown to provide effective relief of
      migraine symptoms in clinical trials, limited data exist directly comparing its
      effectiveness with non-triptan medications. METHODS: Migraineurs aged 18 to 55
      who had been prescribed a new antimigraine drug (rizatriptan 10 mg or a selected
      class of non-triptan oral medications) were recruited to participate in the study
      through a national retail pharmacy chain. Participants completed a baseline
      questionnaire at the enrollment and reported their treatment experiences by
      filling out the treatment diary after using the newly prescribed medication. The
      treatment outcomes of patients receiving rizatriptan were compared with those
      receiving non-triptan medications. Logistic regression analysis was applied to
      test statistical significance with adjustment for potential confounding factors.
      RESULTS: Of the 728 patients who entered the study, 693 (95.2%) completed the
      treatment diary. Patients treated with rizatriptan (192) and non-triptans (501)
      reported the following outcomes, respectively--onset of headache relief within 30
      minutes post-dose: 25% versus 18%; self-defined significant headache relief
      within 2 hours post-dose: 71% versus 54%; pain free or mild pain at 2 hours post
      dose: 58% versus 47%; completely symptom-free within 2 hours of post-dose: 32%
      versus 20%; return to usual activities within 2 hours post-dose: 39% versus 35%;
      and satisfied with treatment: 67% versus 55% (P <.05 in all comparisons with
      exception of returning to usual activities). CONCLUSION: Rizatriptan was
      significantly more effective than non-triptans in the relief of migraine
      headaches for patients obtaining prescribed migraine medications from a retail
      pharmacy. Additional studies at other usual care settings may be needed to
      confirm the findings.

PMID- 15447700
TI  - Unilateral black hairy tongue in trigeminal neuralgia.
AB  - Unilateral hairlike discoloration of the tongue is described in a patient with
      ipsilateral mandibular division trigeminal neuralgia. This unusual physical sign
      coincided with the patient's painful trigger zone and was attributed to
      hypertrophy of keratinized filiform papillae, where guarded avoidance of
      mechanical stimulation over time prevented normal desquamation.

PMID- 15447701
TI  - Familial hemiplegic migraine, neuropsychiatric symptoms, and Erdheim-Chester
      disease.
AB  - We report the occurrence of unilateral cerebral hemisphere edema with subsequent
      cortical laminar necrosis in the setting of familial hemiplegic migraine (FHM)
      and permanent neurologic sequelae after resolution of an attack in 1 patient.
      Contemporaneous with this severe attack of FHM, the patient was found to exhibit
      multiple systemic and neurological symptoms referable to Erdheim-Chester disease
      (a rare non-Langerhans cell histiocytosis) that was confirmed by bone biopsy.
      This case demonstrates the severity possible with a migrainous infarction
      associated with FHM. The co-occurrence of two such rare entities in 1 patient
      suggests a possible relationship.

PMID- 15447702
TI  - Headache profile in patients with idiopathic hypertrophic cranial
      pachymeningitis.
AB  - BACKGROUND: Idiopathic hypertrophic cranial pachymeningitis (IHCP) is an uncommon
      disorder due to localized or diffuse thickening of the dura mater. While headache
      is the most common manifestation, the clinical characteristics of the headache in
      IHCP have not been well characterized. METHODS: From 1996 to 2002, 6 consecutive
      patients with IHCP presenting with headache were reviewed (3 women, 3 men; mean
      age: 49 years). Diagnosis was based on characteristic neuroimaging findings and
      the exclusion of secondary causes of cranial pachymeningitis. This study reported
      the headache characteristics, neuroimaging features, and longitudinal follow-up.
      RESULTS: Chronic daily headache, especially chronic migraine, was the most common
      headache pattern observed (4/6 patients). Lateralization of headache location
      appeared to correlate with the distribution of the hypertrophied dural lesions.
      Diagnostic delay was due to failure to evaluate with gadolinium-enhanced MRI.
      After treatment, headache (5/6, 83%) and neurologic deficits (2/3, 67%) improved
      in most patients; however, follow-up MRIs (n = 5) showed deterioration in 3
      patients. CONCLUSION: The headache of IHCP is typically a chronic daily headache,
      often resembling chronic migraine. Correspondingly, IHCP should be considered in
      the differential diagnosis of refractory chronic daily headache, with or without
      associated cranial neuropathy or other associated neurologic deficits. The
      typical imaging finding on gadolinium-enhanced MRI is localized or diffuse
      pachymeningitis and failure to order a gadolinium-enhanced MRI is the primary
      reason for delayed diagnosis. Despite symptomatic improvement on longitudinal
      follow-up, the MRI abnormalities may not improve in parallel with the clinical
      symptoms.

PMID- 15447703
TI  - Trigeminal schwannoma presenting as daily migraine headache.

PMID- 15447704
TI  - Phosphodiesterase-5 inhibitors and migraine.

PMID- 15447705
TI  - Breast cancer metastasis involving pterygopalatine fossa: a cause of trigeminal
      neuralgia.

PMID- 15447706
TI  - Headaches and pineal cyst: a (more than) coincidental relationship?
AB  - Pineal cysts are common findings in neuroimaging studies. The cysts are more
      frequent in women in their third decade of life. Pineal cysts can be symptomatic,
      headache is the most common symptom. The pineal gland has important physiological
      implications in humans, but little is known about the impact of pineal cysts in
      human physiology. We report 5 headache patients with pineal cyst, 4 women, 1 man,
      mean age 37.6, mean cyst diameter 10.1 mm. Two patients had migraine without
      aura, 1 migraine with aura, 1 chronic migraine, and 1 hemicrania continua. Three
      patients had strictly unilateral headaches. We hypothesize pineal cysts may be
      not incidental in headache patients, inducing an abnormal melatonin secretion.

PMID- 15447707
TI  - Carotid artery dissection in ergotamine abuse.
AB  - The case of a 65-year-old male migraine patient with spontaneous internal carotid
      artery dissection is presented. He had been abusing ergotamine compounds for
      several years on at least 15 days per month. A possible association between
      arterial dissection and ergotamine abuse is discussed.

PMID- 15447708
TI  - Cryptic dental disease causing headache...?

PMID- 15447709
TI  - Migraine and sex hormones: epidemiological data stimulate rethinking of etiologic
      role of estrogen.

PMID- 15447710
TI  - Evaluating triptan usage: a rebuttal.

PMID- 15447711
TI  - Cyproheptadine's antiserotonin effects are responsible for its antimigraine
      activity.

PMID- 15447719
TI  - DNA microarray technology and its applications in dermatology.
AB  - The use of DNA microarray technology in biomedical research has dramatically
      increased during the past years. In the present report, we provide an overview on
      the basic DNA microarray technology and biostatistical methods for gene
      expression analysis. A focus is then put on its applications in dermatological
      research. In recent years, a series of gene expression studies have been
      performed for various dermatological diseases, such as malignant melanoma,
      psoriasis and lupus erythematosus. These analyses have identified interesting
      target genes as well as putative disease susceptibility loci. However, further
      functional studies will be needed for a more complete understanding of the
      pathogenesis of these diseases. This may be performed by means of the recently
      developed RNA interference technology. Besides its role in large-scale gene
      expression studies, DNA microarray technology has proved to be a valuable tool
      for genomic screens of genetic alterations, e.g. single nucleotide polymorphisms.
      These play a role in tumour development and progression, and also function as
      genetic markers for disease susceptibility. Taken together, DNA microarray
      technology opens enormous perspectives for dermatologists. It may help us
      understand the complex pathogenesis of a wide variety of dermatologic diseases
      and identify their genetic background.

PMID- 15447720
TI  - Correlation of psoriasis activity with abundance of CD25+CD8+ T cells: conditions
      for cloning T cells from psoriatic plaques.
AB  - The role of T cells in the pathogenesis of psoriasis is widely acknowledged.
      However, key aspects of their precise function in the disease as well as the
      relative pathogenic contribution of T-cell subsets are still unknown. T-cell
      clones have been isolated from psoriatic plaques but a study of conditions
      affecting the isolation and expansion of T-cell clones from psoriatic skin has
      not been reported to date. Here, we observe a correlation of disease activity
      with the frequency of the CD3(+)CD8(+)CD25(+) subset. We show that prolonged in
      vitro culture changes the phenotypic subset distribution of T-cell lines derived
      from psoriatic skin and that T-cell clones can be isolated by sorting of CD25(+)
      cells emigrated from skin fragments after 7 days. We evaluate various conditions
      affecting expansion of psoriatic T-cell clones in vitro and show that blocking
      apoptosis can facilitate proliferation of activated T-cell clones in vitro. Our
      results indicate a prominent role of the CD8(+)CD25(+) T-cell subset in disease
      pathogenesis and should be useful in the design of experiments aiming at a
      systematic analysis of the specificity of clones present in psoriatic plaques.

PMID- 15447721
TI  - In vivo elimination of CD25+ regulatory T cells leads to tumor rejection of
      B16F10 melanoma, when combined with interleukin-12 gene transfer.
AB  - CD4(+)CD25(+) T cells are an important population that plays a crucial role in
      the maintenance of peripheral self-tolerance. Recently, it was shown that the
      elimination of these cells by in vivo administration of anti-CD25 monoclonal
      antibody (mAb) caused the regression of highly immunogenic tumors in syngeneic
      mice. In this study, we examined whether B16F10 melanoma cells regressed with the
      elimination of CD25(+) regulatory T cells. We found the melanoma cells were not
      affected at all by in vivo anti-CD25 mAb administration alone but tumor rejection
      resulted in all mice when the administration was combined with IL-12 gene
      transfer to tumor cells. In vivo, depletion of natural killer (NK) cells or
      CD8(+) T cells cancelled the tumor rejection. NK-cell depletion allowed IL-12
      transfected B16F10 melanoma (B16/IL-12) to grow from an early stage and resulted
      in a more rapid tumor growth of B16/IL-12 than that in mice without
      administration of anti-CD25 mAb. On the other hand, CD8(+) T-cell depletion did
      not affect the tumor growth in the early phase but allowed B16/IL-12 to grow in
      rather a late phase and resulted in almost the same degree of tumor growth as in
      mice without administration of anti-CD25 mAb. In a previous study, we showed that
      the elimination of CD4(+) T cells enhanced the antitumor effect of B16/IL-12 and
      induced vitiligo-like coat color alteration. Therefore, we also examined the
      frequency of the change to a vitiligo-like coat color in mice showing tumor
      rejection caused by CD25(+) T-cell elimination to compare with the mechanism
      enhancing the antitumor effects by cell elimination. The elimination of CD25(+) T
      cells did not induce vitiligo-like coat color changes, though that of CD4(+) T
      cells induced the change in 60% of mice. Furthermore, we confirmed that
      elimination of CD25(+) T cells did not affect the T-helper (Th) 1/Th2 cytokine
      profile, while that of CD4(+)T cells abrogated the Th2 cytokines (IL-4 and IL-10)
      and resulted in a Th1-dominant cytokine profile in the tumor-draining lymph nodes
      (TDLNs) of B16/IL-12-bearing mice. These results indicate that in vivo depletion
      of CD25(+) regulatory T cells is a potent useful adjuvant in immunotherapy of
      B16F10 melanoma, when combined with IL-12 gene transfer and that the enhancement
      of the antitumor effect by CD25(+) T-cell depletion is mediated through CD8(+) T
      cells and may differ from the enhancing mechanism caused by CD4(+) T-cell
      depletion.

PMID- 15447722
TI  - The role of BMP signalling in the control of ID3 expression in the hair follicle.
AB  - Both the production of the hair shaft in anagen and the initiation of a new hair
      cycle at telogen are the result of reciprocal interactions between the dermal
      papilla and the overlying epithelial cells. Secreted factors, such as those of
      the bone morphogenetic protein (BMP) family, play a crucial role in moderating
      these interactions. Analysis of hair follicles in different stages of the hair
      cycle showed that BMP signalling was only active during anagen and again during
      telogen. During catagen, no BMP signalling occurred in the dermal papilla. ID3, a
      gene expressed in the dermal papilla of both vibrissa and pelage follicles, is a
      BMP target, and as such, we found that ID3 was expressed from the earliest stages
      of morphogenesis. During the hair cycle, ID3 was only expressed in the dermal
      papilla at middle anagen and telogen. To test the significance of ID3 expression
      in the dermal papilla, we cultured dermal papilla cells and found that ID3
      expression fell significantly after a single passage. ID3 expression was returned
      to in vivo levels in low- and high-passage cells by culturing to high confluence
      or by the addition of BMP4. These studies reinforce the requirement for active
      BMP signalling and cell-cell contacts in the dermal papilla during specific
      stages in the hair cycle.

PMID- 15447723
TI  - Therapeutic effects of gemcitabine on cutaneous manifestations in an Adamantiades
      Behcet's disease-like mouse model.
AB  - The aim of this work was to study the effects and side effects of gemcitabine
      (2',2'-difluorodeoxycytidine, dFdC), a pyrimidine synthesis inhibitor, on skin
      lesions of a herpes simplex virus (HSV)-induced Adamantiades-Behcet's disease
      (ABD)-like mouse model. For the dose-escalation study, ICR mice were treated
      intraperitoneally with dFdC over 5 days. For the efficacy study, ICR mice were
      inoculated with HSV and classified as having ABD according to a revised Japanese
      classification, and then 18 ABD mice were randomly assigned to placebo, 0.06 or
      0.12 microg of dFdC/day over 5 days. Serum levels of interleukin-4 (IL-4), IL-6,
      IL-10, interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha)
      were determined using enzyme-linked immunosorbent assay. After application of 3
      microg of dFdC over 5 days, alanine aminotransferase increased (P = 0.032), but
      all other kidney and liver parameters were unchanged. In ABD mice, 5 days of dFdC
      treatment with 0.06 or 0.12 microg of dFdC/day resulted in a dose-dependent
      improvement of cutaneous manifestations by more than 60% (P = 0.017). There was
      no significant change in cytokine levels, and none of the cytokine levels
      correlated with response to treatment. Moreover, dFdC shows promising effects to
      improve cutaneous lesions in the HSV-induced ABD-like mouse model. In this animal
      model, effects of dFdC on the cytokine profile remained inconclusive.

PMID- 15447724
TI  - Limitations of human occipital scalp hair follicle organ culture for studying the
      effects of minoxidil as a hair growth enhancer.
AB  - Minoxidil induces new hair growth in approximately one-third of patients with
      androgenetic alopecia after 1 year of treatment. With several conflicting reports
      in the literature based on small-scale studies, the current study aimed to
      clarify whether organ culture of human scalp anagen VI hair follicles is a
      suitable in vitro test system for reproducing, and experimentally dissecting, the
      recognized in vivo hair-growth-promoting capacity of minoxidil. Hair shaft
      elongation was studied in terminal anagen VI hair follicles microdissected from
      the occipital scalp of 36 healthy adults. A total of 2300 hair follicles,
      approximately 65 per individual, were tested using modifications of a basic organ
      culture protocol. It is shown here that minoxidil does not significantly increase
      hair shaft elongation or the duration of anagen VI in ex vivo culture despite
      several enhancements on the conventional methodology. This disparity to what is
      seen clinically in minoxidil responders may be explained by the following: (i)
      use of occipital (rather than frontotemporal or vertex) hair follicles; (ii) use
      of, already maximally growing, anagen VI hair follicles; (iii) a predominance of
      hair follicles from minoxidil unresponsive-donors; (iv) use of minoxidil rather
      than its sulfate metabolite; and/or (v) use of a suboptimal minoxidil dosage.
      This disparity questions the usefulness of standard human hair follicle organ
      culture in minoxidil research. Unexpectedly, minoxidil even inhibited hair shaft
      elongation in the absence of insulin, which may indicate that the actual hair
      growth-modulatory effects of minoxidil depend on the concomitant local
      presence/absence of other growth modulators.

PMID- 15447725
TI  - Mutation spectra of epidermal p53 clones adjacent to basal cell carcinoma and
      squamous cell carcinoma.
AB  - Foci of normal keratinocytes overexpressing p53 protein are frequently found in
      normal human skin. Such epidermal p53 clones are common in chronically sun
      exposed skin and have been suggested to play a role in skin cancer development.
      In the present study, we have analyzed the prevalence of p53 mutations in
      epidermal p53 clones from normal skin surrounding basal cell carcinoma (BCC) and
      squamous cell carcinoma (SCC). Using laser-assisted microdissection, 37 epidermal
      p53 clones adjacent to BCC (21) and SCC (16) were collected. Genetic analysis was
      performed using a multiplex/nested polymerase chain reaction followed by direct
      DNA sequencing of p53 exons 2-11. In total, 21 of 37 analyzed p53 clones
      consisted of p53-mutated keratinocytes. The identified mutations were located in
      p53 exons 4-8, corresponding to the sequence-specific DNA-binding domain. All
      mutations were missense, and 78% displayed a typical ultraviolet signature. The
      frequency of p53 mutations was similar in skin adjacent to BCC compared to SCC.
      The presented data confirm and extend previous knowledge on the genetic
      background of epidermal p53 clones. The mutation spectra found in epidermal p53
      clones resemble that of non-melanoma skin cancer. Approximately, 40% of the
      epidermal p53 clones lacked an underlying p53 mutation, suggesting that other
      genetic events in genes up- or downstream of the p53 gene can generate foci of
      normal keratinocytes overexpressing p53 protein.

PMID- 15447727
TI  - Intercellular junctions in normal epidermis.

PMID- 15447728
TI  - Dysfunction of keratinocyte adhesion.

PMID- 15447729
TI  - Developmental signals in skin morphogenesis.

PMID- 15447730
TI  - Animal models of human skin disease.

PMID- 15447731
TI  - Connexin mutations in human disease.

PMID- 15447732
TI  - Role of integrins in tumor invasion and metastasis.

PMID- 15447733
TI  - Experimental human pain models: a review of standardised methods for preclinical
      testing of analgesics.
AB  - Treatment of pain is one of the major challenges in clinical medicine. However,
      it is often difficult to evaluate the effect of a treatment, as the many symptoms
      of the underlying diseases often confound this assessment. Furthermore, as the
      pain mechanisms in many diseases are poorly understood, the limited successful
      trial and error approach is most often used in the selection of analgesics.
      Hence, there is a need for new methods in the characterization and treatment of
      pain. Human experimental pain models offer the possibility to explore the pain
      system under controlled settings. The models can also be used to screen the
      analgesic profiles of drugs targeted to treat pain. This review gives a brief
      introduction to the methods used to evoke and assess pain in the skin, muscle and
      viscera. New methods using multimodal stimulation and activation of central pain
      mechanisms can to a higher degree mimic the clinical situation, and such methods
      are recommended in the future screening of analgesics. Examples of the use of
      experimental pain models in the testing of analgesics are given. With these
      models the therapeutic spectrum may be defined from a differentiated knowledge on
      the effect of drugs on the pain system. Such information may be used in the
      future guidelines for trials and clinical use of analgesics.

PMID- 15447734
TI  - Omeprazole treatment of Korean patients: effects on gastric pH and gastrin
      release in relation to CYP2C19 geno- and phenotypes.
AB  - This study aimed to investigate the effect of omeprazole on intragastric pH and
      gastrin release as well as the plasma concentration of omeprazole in relation to
      CYP2C19 genotypes after repeated doses in Korean patients. Twenty-six Korean
      patients with acid related disease were genotyped for CYP2C19 by allele specific
      PCR (wt/wt, CYP2C19*1/*1; wt/mut, CYP2C19*1/*2 or *1/*3; mut/mut, CYP2C19*2/*2,
      *2/*3 or *3/*3). Intragastric pH was monitored during 24 hr, and the plasma
      concentrations of omeprazole, hydroxyomeprazole, omeprazole sulfone and meal
      stimulated gastrin were measured during 4 hr before and after 8 consecutive daily
      doses of 20 mg omeprazole. Unexpectedly the AUCs of omeprazole in the three
      genotypes were similarly high on Day 8. The mean 24 hr pH increased significantly
      in all three genotypes (paired t-test; P<0.0001), and the AUCs (4 hr) of gastrin
      in all patients increased markedly from 129+/-73 to 298+/-142 pMhr (P<0.0001).
      However, there was no statistically significant difference between the three
      genotypes in the mean pH and gastrin AUCs on Day 8. After 8 consecutive doses of
      20 mg omeprazole, the gastric pH and the plasma gastrin were increased
      significantly in all three CYP2C19 genotypes, which were confirmed by high plasma
      concentrations of omeprazole in all three genotype groups. We suggest that the
      reason why the wt/wt had high concentrations of omeprazole similar to those in
      the other two genotype groups is that some of them were old with low CYP2C19
      activity. In these patients omeprazole accumulated from the first to the eighth
      dose similar to that in the heterozygotes.

PMID- 15447735
TI  - Effect of itraconazole on the pharmacokinetics of inhaled lidocaine.
AB  - Lidocaine is metabolized by cytochrome P450 3A4 and 1A2 enzymes (CYP3A4 and
      CYP1A2) in vitro. However, their relative contribution to the elimination of
      lidocaine depends on lidocaine concentration. We have studied the effect of a
      potent CYP3A4 inhibitor, itraconazole, on the pharmacokinetics of inhaled
      lidocaine in ten healthy volunteers using a randomized, two-phase cross-over
      study design. The interval between the phases was four weeks. The subjects were
      given orally itraconazole (200 mg once a day) or placebo for four days. On day 4,
      each subject inhaled a single dose of 1.5 mg/kg of lidocaine by nebulizer. Plasma
      samples were collected until 10 hr and the concentrations of lidocaine and its
      major metabolite monoethylglycinexylidide were measured by gas chromatography.
      The areas under the lidocaine and monoethylglycinexylidide concentration time
      curves were similar during both phases. No statistically significant differences
      were observed in any of the pharmacokinetic parameters; peak concentrations,
      concentration peak times or elimination half-lives of lidocaine or
      monoethylglycinexylidide. The clinical implication of this study is that no
      lidocaine dosage adjustments are necessary if it is used to prepare the airway
      prior to endoscopic procedures or intubation in patients using itraconazole or
      other inhibitors of CYP3A4.

PMID- 15447736
TI  - Effect of nortriptyline on intracellular Ca2+ handling and proliferation in human
      osteosarcoma cells.
AB  - The effect of the antidepressant nortriptyline, on bone cells is unknown. In
      human osteosarcoma MG63 cells, the effect of nortriptyline on intracellular Ca2+
      concentration ([Ca2+]i) and proliferation was measured by using fura-2 and
      tetrazolium, respectively. Nortriptyline (> or = 10 microM) caused a [Ca2+]i rise
      in a concentration-dependent manner (EC50 = 200 microM). Nortriptyline-induced
      [Ca2+]i rise was prevented by 60% by removal of extracellular Ca2+ but was not
      altered by voltage-gated Ca2+ channel blockers. In Ca2+ -free medium,
      thapsigargin, an inhibitor of the endoplasmic reticulum Ca2+ -ATPase, caused a
      monophasic [Ca2+]i rise, after which the increasing effect of nortriptyline on
      [Ca2+]i was abolished; also, pretreatment with nortriptyline abolished
      thapsigargin-induced [Ca2+]i increase. U73122, an inhibitor of phospholipase C,
      did not affect nortriptyline-induced [Ca2+]i rise; however, activation of protein
      kinase C decrease nortriptyline-induced [Ca2+]i rise by 32%. Overnight incubation
      with 50 and 100 microM nortriptyline killed 78% and 97% of cells, respectively;
      while 10 microM nortriptyline had no effect. These data suggest that
      nortriptyline rapidly increases [Ca2+]i in human osteosarcoma cells by
      stimulating both extracellular Ca2+ influx and intracellular Ca2+ release, and is
      cytotoxic at high concentrations.

PMID- 15447737
TI  - Protective effects of vitamin A and vitamin E succinate against 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD)-induced body wasting, hepatomegaly, thymic
      atrophy, production of reactive oxygen species and DNA damage in C57BL/6J mice.
AB  - The protective effect of vitamin A and vitamin E succinate against 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD)-induced acute toxicity and measures of
      oxidative stress was studied. Ten mice were treated with either vitamin A (50
      mg/kg every other day for eight days) or vitamin E succiante (150 mg/kg/day
      followed by a dose of 40 mg/kg/day for five additional days). Half of each of the
      above groups of animals received TCDD on day 4. Five mice received corn oil or
      TCDD alone. After five days of TCDD treatment, antioxidant combination treatment
      with vitamin A and TCDD or vitamin E succinate and TCDD resulted in a significant
      reduction in indicators of acute toxicity including the decrease in total body
      and thymus weight as compared to TCDD alone (P<0.05). The combination treatment
      produced also a significant reduction in the increase in liver weight as compared
      to TCDD only (P<0.05). Following one day of treatment with 50 microg TCDD/kg,
      vitamin A and vitamin E succinate produced a significant decrease in the
      production of superoxide anion by peritoneal lavage cells (P<0.05) and in DNA
      single strand breaks in the same cells (P<0.05) as assessed by the reduction of
      cytochrome c and the alkaline elution technique, respectively. A significant
      decrease in DNA-single strand breaks in peritoneal lavage cells was observed
      following 5 days treatment with 50 microg TCDD/kg (P<0.05). The results indicate
      a potential role for oxidative stress in the acute toxicity of TCDD and a
      protective effect for vitamin A and vitamin E succinate in the overall toxicity
      of TCDD including measures of oxidative stress.

PMID- 15447738
TI  - Effects of perinatal combined exposure to 1,4-dichlorobenzene and 1,1-dichloro-2,
      2-bis (p-chlorophenyl) ethylene (p,p'-DDE) on rat female offspring.
AB  - 1,4-Dichlorobenzene (DCB) is used as an air freshener and a moth repellent and 1,
      1-dichloro-2, 2-bis (p-chlorophenyl) ethylene (p,p'-DDE) is a persistent
      metabolite of 1, 1, 1-trichloro-2, 2-bis (p-chlorophenyl) ethane (DDT) previously
      used as a pesticide. DCB concentrations of residential air and oral p,p'-DDE
      intake via marine products are demonstrated to be higher in Japan than elsewhere.
      Consequently, human foetuses and neonates may be exposed to DCB and p,p'-DDE via
      the mother. Therefore, the combined effects of DCB and p,p'-DDE have been
      investigated in rat female offspring of dams after ingestion of these
      contaminants. No deteriorated reproductive outcomes of dams and developmental
      effects on female offspring were observed following oral administration of 25 ppm
      DCB (approximately 2 mg/kg) and/or 125 ppm p,p'-DDE (approximately 10 mg/kg) to
      dams. In this study, the thymus weight of female offspring was preserved by DCB
      at 6 weeks of age though the biological relevance remains unknown. Simultaneous
      administration of p,p'-DDE with DCB inhibited this phenomenon, through a
      mechanism still to be elucidated.

PMID- 15447740
TI  - The Journal's impact increases!

PMID- 15447739
TI  - In vitro optimization of structure activity relationships of analogues of A
      331440 combining radioligand receptor binding assays and micronucleus assays of
      potential antiobesity histamine H3 receptor antagonists.
AB  - A-331440 [4'-[3-(3(R)-(dimethylamino)-pyrrolidin-1-yl)-propoxy]-biphenyl-4
      carbonitrile], a potent and selective antagonist of histamine H3 receptors,
      yielded positive results in an in vitro micronucleus assay, predictive of
      genotoxicity in vivo. Because this compound has highly favourable properties and
      potential as an antiobesity agent, new compounds of this general chemical class
      were sought that would retain or improve upon the high potency and selectivity of
      A-331440 for H3 receptors, but would lack the potential for genotoxicity obtained
      with that compound. Our working hypothesis was that the biphenyl rings in A
      331440 might contribute to interactions with DNA and thereby predispose toward
      genotoxicity. Toward this end, several analogues were prepared, with substituents
      introduced onto the biaryl ring to alter the orientation, electronegativity, and
      polarity of this moiety, and were tested for their radioligand binding potency
      and selectivity and their propensity to induce genotoxicity in the in vitro
      micronucleus assay. Using this strategy, novel compounds were discovered that
      retained or improved upon the potency and selectivity of A-331440 for H3
      receptors and were devoid of genotoxicity in vitro. Of these, the simple mono-
      and di-fluorinated analogues (A-417022 [4'-[3-[(3R)-3-(dimethylamino)-1
      pyrrolidinyl]propoxy]-3'-fluoro-1,1'-biphenyl-4-carbonitrile] and A-423579 [4'-[3
      [(3R)-3-(dimethylamino)-1-pyrrolidinyl]-propoxy]-3',5'-difluoro-1,1'-biphenyl-4
      carbonitrile], respectively) were found to bind to H3 receptors at least as
      potently as A-331440, while lacking genotoxicity in the micronucleus assay. The
      reason of the lack of genotoxicity of the fluorinated analogues is unclear, but
      is especially noteworthy in light of the general principle that fluorine and
      hydrogen are very similar in size. Therefore, these fluorinated analogues of A
      331440 represented the most potent and potentially safest compounds for further
      evaluation as antiobesity leads. Preliminary findings with one of these examples,
      A-417022, in a mouse model of obesity are presented.

PMID- 15447741
TI  - Ethical issues in genetic testing.

PMID- 15447742
TI  - Clinical examination of the gastrointestinal system in the 21st century--is the
      emphasis right?

PMID- 15447743
TI  - Poison bottles.

PMID- 15447744
TI  - Proton pump inhibitors are associated with reduced incidence of dysplasia in
      Barrett's esophagus.
AB  - BACKGROUND AND AIMS: Esophageal acid exposure is important in the pathogenesis of
      Barrett's esophagus (BE), and possibly in the progression of BE to dysplasia and
      carcinoma. The aim of this study is to compare the development of dysplasia in BE
      patients treated with or without proton pump inhibitor (PPI) or histamine 2
      receptor antagonist (H2RA). METHODS: We analyzed prospectively collected data by
      a single endoscopist on patients with BE in a VA (Veterans Affairs) setting over
      a 20-yr time period (1981-2000). A pathologist used standard criteria to diagnose
      BE/dysplasia. Pharmacy information after 1994 was retrieved from a computerized
      database, and from research files for the period before that. The receipt and the
      duration of H2RA and/or PPI use was compared between those with and without
      dysplasia. The incidence of dysplasia was examined in a Kaplan-Meier survival
      analysis stratified by PPI treatment status, and the risk of dysplasia was
      examined in a Cox multiple regression analysis controlling for demographic
      features, length of BE, and the year of BE diagnosis. RESULTS: We analyzed data
      for 236 unique veteran patients with a mean age at BE diagnosis of 61.5 yr, 86%
      Caucasian, and 98% male. During 1,170 patient-yr of follow-up, 56 patients
      developed dysplasia giving an annual incidence rate of 4.7%. Of those, 14 had
      high-grade dysplasia. The cumulative incidence of dysplasia was significantly
      lower among patients who received PPI after BE diagnosis than in those who
      received no therapy or H2RA; log rank test (p < 0.001). Furthermore, among those
      on PPIs, a longer duration of use was associated with less frequent occurrence of
      dysplasia. In multivariate analysis, the use of PPI after BE diagnosis was
      independently associated with reduced risk of dysplasia, hazards ratio: 0.25 (95%
      CI 0.13-0.47), p < 0.0001. Longer segments of BE and Caucasian race were other
      independent risk factors for developing dysplasia. In general, similar findings
      were observed when only cases with high-grade dysplasia were analyzed.
      CONCLUSIONS: These results indicate that PPI therapy is associated with a
      significant reduction in the risk of developing dysplasia in patients with BE.
      However, more studies are required to confirm this finding.

PMID- 15447745
TI  - Acid suppression and adenocarcinoma of the esophagus: cause or cure?
AB  - In this issue El-Serag et al. present a retrospective study which shows that
      patients with Barrett's esophagus and no dysplasia who were prescribed PPIs had a
      lesser rate of developing dysplasia than patients who were not prescribed PPIs.
      Acid suppression has been proposed both as a cause and a cure for the "epidemic"
      of adenocarcinoma of the esophagus, which has been noted in the United States.
      The article and the current evidence related to acid suppression and
      adenocarcinoma of the esophagus are reviewed.

PMID- 15447746
TI  - DNA abnormalities as marker of risk for progression of Barrett's esophagus to
      adenocarcinoma: image cytometric DNA analysis in formalin-fixed tissues.
AB  - OBJECTIVES: To examine DNA content abnormalities in patients with Barrett's
      esophagus (BE) who progress to esophageal adenocarcinoma, using image cytometric
      DNA analysis (ICDA) of formalin-fixed tissues. METHODS: Studies were performed on
      archived biopsies of BE patients' undergoing endoscopic surveillance before
      developing adenocarcinoma. A comparison group consisted of BE patients' free of
      cancer during a follow-up period of over 9 yr. Tissue sections were analyzed for
      the degree of dysplasia and for DNA content abnormalities, using image cytometry.
      Additional patients were also analyzed in a cross-sectional study of 56 BE cases
      with and without dysplasia, including 12 cases of adenocarcinoma. RESULTS: Five
      patients developed adenocarcinoma during follow-up and earlier biopsies obtained
      before cancer diagnosis showed specialized intestinal metaplasia (SIM) followed
      by low-grade dysplasia (LGD) in one, SIM followed by high-grade dysplasia (HGD)
      in one, LGD in two, and HGD in one case. All five showed some DNA abnormality at
      baseline or in interval biopsies. In the comparison group, five of seven patients
      showed normal diploid DNA at baseline and on follow-up biopsies. One patient
      initially had diploid DNA, but developed aneuploidy 11 yr later. Another case
      initially had aneuploidy, but was diploid on follow-up. Overall, DNA
      abnormalities were found in 13% of cases with SIM without dysplasia, 60% with
      LGD, 73% with HGD, and 100% with adenocarcinoma. CONCLUSIONS: (i) Image
      cytometric DNA analysis is a useful method to examine DNA abnormalities in
      formalin-fixed tissues and may be more sensitive in predicting progression to
      adenocarcinoma than HGD. (ii) Histological dysplasia of any grade and DNA
      abnormalities, help identify BE patients at high risk for adenocarcinoma.

PMID- 15447747
TI  - Gastroesophageal junction smooth muscle remodeling after endoluminal
      gastroplication.
AB  - OBJECTIVES: Endoluminal gastroplication (ELGP) is an endoscopic mucosal suturing
      procedure for the treatment of gastroesophageal reflux disease. The antireflux
      mechanism of the mucosal suture remains poorly understood. The aim of this study
      is to investigate any morphologic changes in the smooth muscle layer induced by
      the mucosal sutures placed at the gastroesophageal junction. METHODS: ELGPs were
      performed using endoscopic suturing devices with placement of two or three
      circumferential sutures within 2 cm of the squamocolumnar junction. Eight
      patients with subsequent symptom resolution underwent endoscopic ultrasound (EUS)
      to evaluate the muscularis propria layer at the gastroesophageal junction. A
      swine model was used for EUS and histopathologic correlation study. Six control
      and 15 ELGP pigs were evaluated with EUS and histological examination of the
      gastroesophageal junction smooth muscle layer. RESULTS: Focal thickening of the
      muscularis propria layer near the suture region (2.3 +/- 0.4 mm vs 1.4 +/- 0.3
      mm, p < 0.01) was found in eight patients with symptomatic resolution. In ELGP
      pigs, the smooth muscle layer thickness increased by 2.6 mm near the suture site
      by EUS. By histology, the total and circular smooth muscle layer thickness
      increased by 2.1 mm and 1.9 mm, respectively. CONCLUSIONS: Focal thickening of
      smooth muscle layer occurs at the gastroesophageal junction after ELGP in
      patients with gastroesophageal reflux disease. This finding was reproduced in a
      swine model and localized hypertrophy was found to be entirely due to an increase
      in the circular smooth muscle layer.

PMID- 15447748
TI  - Relationship between partial gastric volumes and dyspeptic symptoms in
      fundoplication patients: a 3D ultrasonographic study.
AB  - OBJECTIVES: Impaired gastric accommodation may induce dyspeptic symptoms in
      postfundoplication patients. Our aim was to assess the effect of a meal on total
      and partial gastric volumes in relation to dyspeptic symptoms in both dyspeptic
      and nondyspeptic fundoplication patients using three-dimensional (3D)
      ultrasonography. METHODS: Eighteen postfundoplication patients of whom eight with
      and ten without dyspeptic symptoms and eighteen controls were studied. Three
      dimensional ultrasonographic images of the stomach were acquired and symptoms
      were scored while fasting and at 5, 15, 30, 45, and 60 min after ingesting of a
      500-ml liquid meal. From the 3D ultrasonographic images of the stomach the total,
      proximal, and distal gastric volumes were computed. RESULTS: Dyspeptic and
      nondyspeptic fundoplication patients exhibited similar total gastric volumes at 5
      min postprandially compared to controls, whereas smaller total gastric volumes
      were observed from 15 to 60 min postprandially (p = 0.007 and p < 0.001,
      respectively). Postprandial proximal/total gastric volume ratios were markedly
      reduced in both dyspeptic (0.39 +/- 0.016; p < 0.05) and nondyspeptic (0.38 +/-
      0.016; p < 0.01) fundoplication patients compared to controls (0.47 +/- 0.008).
      In contrast, distal/total gastric volume ratios were larger in dyspeptic
      fundoplication patients (0.14 +/- 0.008) compared to both nondyspeptic
      fundoplication patients (0.11 +/- 0.007); p < 0.05) and controls (0.07 +/-
      0.003); p < 0.001). Dyspeptic fundoplication patients had a higher postprandial
      score for fullness, nausea, and pain than nondyspeptic patients (p < 0.05) and
      controls (p < 0.05). Meal-induced distal gastric volume increase correlated
      significantly with the increase in fullness (r = 0.68; p < 0.01). CONCLUSIONS:
      After a liquid meal, fundoplication patients exhibit a larger volume of the
      distal stomach compared with controls. Distal stomach volume was more pronounced
      in dyspeptic fundoplication patients and related with the increase in
      postprandial fullness sensations.

PMID- 15447749
TI  - Serological markers for gastric atrophy in asymptomatic patients infected with
      Helicobacter pylori.
AB  - OBJECTIVE: Atrophic gastritis is a precancerous condition that is commonly caused
      by chronic Helicobacter pylori (H. pylori) infection. This blinded, controlled
      study was designed to determine if serum gastrin and pepsinogens were reliable
      markers of atrophy in asymptomatic patients. METHODS: One hundred and forty-seven
      asymptomatic patients underwent endoscopy with multiple gastric biopsies obtained
      for histology, culture, and rapid urease test. Fasting serum gastrin (total and G
      17) and serum pepsinogens (I-II) were determined by standard immunoassays.
      Gastric atrophy was histologically assessed in accordance with internationally
      accepted criteria; three main patterns of gastritis were distinguished: (a)
      nonatrophic gastritis, (b) atrophic antrum-restricted and antrum-predominant
      gastritis, and (c) corpus-restricted gastritis. Receiving operating
      characteristic (ROC) analysis was used to determine the best cut-off for each
      serum test in nonatrophic gastritis versus antrum-restricted/antrum-predominant
      atrophic gastritis. RESULTS: No significant differences in serum gastrin and
      pepsinogens I-II were detected in nonatrophic gastritis versus patients with
      antrum-restricted/antrum-predominant atrophic gastritis. The positive likelihood
      ratios for an abnormal serum test to detect antrum-restricted/antrum-predominant
      atrophy in the gastric body were total serum gastrin 2.13 (95% CI 0.99, 4.6),
      gastrin-17: 1.55 (95% CI 0.75, 36.17), pepsinogen I: 2.74 (1.4, 5.4), pepsinogen
      II: 1.74 (1.27, 2.39), and the ratio of pepsinogen I and II: 1.8 (1.2-2.8).
      Negative likelihood ratios ranged from 0.20 to 0.65. CONCLUSION: In an
      asymptomatic population, serum gastrin (total and G-17) and pepsinogens I-II (and
      their ratio) do not discriminate nonatrophic versus antrum-restricted/predominant
      atrophic gastritis.

PMID- 15447750
TI  - Elevated concentrations of alpha-defensins in gastric juice of patients with
      Helicobacter pylori infection.
AB  - OBJECTIVE: Defensins (alpha- and beta-defensins) are endogenous antimicrobial
      peptides. Little is known about alpha-defensins during Helicobacter pylori
      infection. METHODS: The concentrations of human neutrophil peptides (HNP-1, -2,
      and -3), the major components of neutrophils-derived alpha-defensins, were
      measured by radioimmunoassay (RIA) in plasma and gastric juice of 61 H. pylori
      infected and 33 uninfected subjects, and before and after anti-H. pylori
      treatment in 12 patients with H. pylori-associated gastritis. Interleukin (IL)-8
      concentrations in gastric juice were measured by enzyme-linked immunosorbent
      assay. Histological grades of gastritis and neutrophil counts (/mm(2))
      infiltrating in the gastric mucosa were determined using two biopsy specimens
      taken from the antrum and corpus. Immunohistochemistry and reverse-phase high
      performance liquid chromatography (RP-HPLC) were used to identify HNPs 1-3.
      RESULTS: HNP 1-3 concentrations in gastric juice were significantly higher in H.
      pylori-positive than in H. pylori-negative patients and significantly decreased
      after cure. HNP 1-3 concentrations in gastric juice correlated with IL-8 levels
      and neutrophil densities in the gastric mucosa and were associated with
      histological degree of gastritis, especially the grades of activity. Intense
      immunoreactivity for anti-HNPs 1-3 antiserum was noted in infiltrating
      neutrophils in H. pylori-infected mucosa. In RP-HPLC analysis, all of the HNP 1-3
      molecules were identified as their mature forms. Plasma HNP 1-3 concentrations
      were similar in H. pylori-infected and non-infected groups and showed no
      correlations with other parameters. CONCLUSIONS: We demonstrated significantly
      elevated levels of HNPs 1-3 in gastric juice during H. pylori infection. The
      elevation of HNPs is presumably secondary to H.pylori-associated gastric
      inflammation involving neutrophil infiltration.

PMID- 15447751
TI  - Prospective comparison of contrast enhanced CT colonography and conventional
      colonoscopy for detection of colorectal neoplasms in a single institutional study
      using second-look colonoscopy with discrepant results.
AB  - BACKGROUND: Colorectal cancer is the second leading cause of death from cancer in
      Western countries. Early detection by colorectal cancer screening can effectively
      cut its mortality rate. CT colonography represents a promising, minimally
      invasive alternative to conventional methods of colorectal carcinoma screening.
      AIMS: The purpose of this prospective single institutional study was to compare
      the abilities of routine clinical CT colonography and conventional colonoscopy to
      detect colorectal neoplasms using second-look colonoscopy to clarify discrepant
      results. PATIENTS AND METHODS: CT colonography was performed in 100 symptomatic
      patients using contrast enhanced multidetector CT followed by conventional
      colonoscopy on the same day. If results were discrepant, a second-look
      colonoscopy was performed after unblinding. CT colonographic findings were
      compared with those of conventional colonoscopy. RESULTS: Conventional
      colonoscopy found 122 colorectal neoplasms in 49 patients. The overall
      sensitivity of CT colonography at detecting patients with at least one polyp 6 mm
      or larger was 76% and its specificity was 88%. Its by-patient sensitivity for
      polyps 10 mm or larger was 95% and its specificity was 98%. By-polyp
      sensitivities were 71% for polyps 10 mm or larger, and 61% for polyps 6 mm or
      larger. A second-look colonoscopy was performed in 19 patients and two initial
      false-positive findings of CT colonography were reclassified as true-positive.
      For conventional colonoscopy, this produced a by-polyp sensitivity of 94% for
      detection of lesions 6 mm and larger. CONCLUSIONS: CT colonography had both a
      high by-patient sensitivity and specificity for detection of clinically important
      colorectal neoplasms 10 mm or larger. This suggests that CT colonography has the
      potential to become a valuable clinical screening method for colorectal
      neoplasms.

PMID- 15447752
TI  - Usefulness of a small-caliber, variable-stiffness colonoscope as a backup in
      patients with difficult or incomplete colonoscopy.
AB  - OBJECTIVES: Although variable-stiffness colonoscopes have been developed,
      difficult or incomplete colonoscopies occasionally occur. The aim of this study
      was to evaluate the usefulness of a small-caliber, variable-stiffness colonoscope
      (scVSC) as a backup in patients with difficult or incomplete colonoscopies.
      METHODS: First, we retrospectively reviewed the cecal intubation rate of
      colonoscopies in which an adult standard colonoscope (AC) was immediately
      switched to an scVSC in all patients in whom a colonoscopy with an AC was
      incomplete. Second, 374 consecutive patients were randomized to undergo
      colonoscopy with a pediatric variable-stiffness colonoscope (PVSC, n = 123), AC
      (n = 125), or scVSC (n = 126). The scVSC was used by the same endoscopist to
      reattempt colonoscopy immediately after colonoscopy with a PVSC or an AC had been
      assessed as difficult or incomplete. The cecal intubation rate and time and the
      ancillary maneuvers used were evaluated. RESULTS: Fifty-two (2.5%) of the 2,056
      attempted colonoscopies with an AC did not reach the cecum. Fifty-one of the 52
      patients (98.1%) had complete colonoscopies after the switch from the AC to the
      scVSC. The initial intubation rate and time were not statistically different
      among the groups: PVSC, 95% and 6.8 min; AC, 91% and 7.5 min; and scVSC, 98% and
      8.2 min. Cecal intubation was achieved in all five patients (100%) and in 10 out
      of 11 (91%) patients, respectively, after the PVSC or AC was switched to the
      scVSC. CONCLUSIONS: The completion rate markedly improved after switching from an
      AC or PVSC to an scVSC in difficult or incomplete colonoscopies, although the
      scVSC does not appear to offer any distinct advantage over the AC or PVSC for
      routine colonoscopies.

PMID- 15447753
TI  - Evaluation of polyp detection in relation to procedure time of screening or
      surveillance colonoscopy.
AB  - BACKGROUND AND OBJECTIVES: Multiple factors influence the yield of colonoscopy
      for the detection of neoplasia. Few studies have addressed the impact of
      colonoscopy duration on procedure yield. The aim of our study was to determine
      whether endoscopist-specific procedure times correlate with the number and
      clinical significance of polyps detected at screening or surveillance
      colonoscopy. METHODS: Procedural data from screening or surveillance
      colonoscopies performed at Mayo Clinic, Rochester MN, between January 1, 1996 and
      June 30, 2000, were reviewed. Individual endoscopists were characterized by their
      personal endoscopist procedure mean time (EPMT) to perform a negative
      colonoscopy. Procedure time included patient's consent and sedation. EPMT was
      then correlated with individual polyp detection rates. RESULTS: Overall, 10,159
      colonoscopies were reviewed of which 4,312 (42.4%) yielded polyps. Polyp
      detection varied among endoscopists between 19.0% and 62.3%. There was a close
      correlation between EPMT and polyp yield (all sizes), r = 0.64, although
      correlation was weaker for polyps >10 mm (r = 0.42) and polyps >20 mm (r = 0.20).
      On multivariate analysis, longer mean endoscopist time was associated with
      colonic lesion detection, OR = 1.54 (95% CI 1.37-1.62). Longer mean procedure
      duration demonstrated a looser association with identification of polyps >10 mm,
      OR = 1.40 (1.19-1.64) and polyps >20 mm, OR = 1.03 (0.74-1.43). CONCLUSIONS:
      There is a direct correlation between colonoscopy procedure time and yield, with
      a three-fold variation of polyp detection rates. These results should prompt
      future prospective studies assessing the impact of colonoscopic withdrawal time
      on lesion detection.

PMID- 15447754
TI  - Beneficial effects of tumor necrosis factor-alpha inhibition by pentoxifylline on
      clinical, biochemical, and metabolic parameters of patients with nonalcoholic
      steatohepatitis.
AB  - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) has been incriminated to play
      an important role in the pathogenesis of nonalcoholic steatohepatitis (NASH).
      Pentoxifylline, a TNF-alpha inhibitor could prove useful in treating patients
      with NASH. METHODS: Eighteen patients (mean age, 34 +/- 7.8 yr) with
      histologically proven NASH and with persistently elevated ALT (>1.5 times) were
      given pentoxifylline at a dosage of 400 mg t.i.d. for 6 months. No lipid-lowering
      agent or antioxidants were concurrently advised. RESULTS: Impaired fasting
      glycemia, impaired glucose tolerance, diabetes mellitus, and hypertriglyceridemia
      were noted in 6, 35, 17, and 53% of the patients, respectively. After 6 months of
      therapy, fatigue improved (55.6 vs 20%, p= 0.016), but serum triglyceride (182 +/
      66 vs 160 +/- 55 mg/dl, p= 0.397), cholesterol (173 +/- 46 vs 162 +/- 40 mg/dl,
      p= 0.440), and body mass index (BMI) (27.3 +/- 3.1 vs 26 +/- 3.1 kg/m(2), p=
      0.087) remained unchanged. Mean AST (66 +/- 29 vs 33 +/- 11 IU/l, p < 0.0001) and
      ALT (109 +/- 44 vs 47 +/- 20 IU/l, p < 0.0001) reduced significantly. ALT
      normalized in 23% at month 1 (p= 0.125), 35% at month 2 (p= 0.125), and 60% at
      month 6 (p= 0.008) of treatment. The insulin resistance index assessed by
      homeostatic metabolic assessment (HOMA(IR)) improved (5.1 +/- 3.4 vs 2.6 +/- 2, p
      = 0.046) and the serum TNF-alpha reduced significantly after therapy (22.15 +/-
      2.49 vs 17 +/- 2.58 pg/ml, p = 0.011). The drug was well tolerated. CONCLUSIONS:
      In patients with NASH, pentoxifylline therapy effectively achieved significant
      clinical and biochemical improvement with reduction in HOMA(IR). These benefits
      are possibly mediated through suppression of TNF-alpha.

PMID- 15447755
TI  - Acute administration of carvedilol is more effective than propranolol plus
      isosorbide-5-mononitrate in the reduction of portal pressure in patients with
      viral cirrhosis.
AB  - OBJECTIVE: Propranolol is known to decrease portal pressure in cirrhotic patients
      with portal hypertension; however, a substantial number of patients do not
      respond to propranolol administration. The addition of isosorbide-5-mononitrate
      may enhance portal pressure reduction in patients receiving propranolol.
      Carvedilol is a nonselective beta-blocker with alpha(1)-adrenergic blocking
      activity. It has been shown to decrease portal pressure in cirrhotic patients.
      Additionally, carvedilol has a greater portal hypotensive effect than propranolol
      alone in patients with cirrhosis. The current study is aimed at comparing the
      acute hemodynamic effects of carvedilol with the effects of propranolol plus
      isosorbide-5-mononitrate in patients with viral cirrhosis. METHODS: Patients with
      viral cirrhosis were randomly assigned to receive an oral administration of
      carvedilol of 25 mg (n = 11) or an oral administration of propranolol 40 mg plus
      isosorbide-5-mononitrate 20 mg (n = 11). Hemodynamic values were measured at
      basal and 90 min after drugs administration. RESULTS: Both carvedilol and
      propranolol plus isosorbide-5-mononitrate significantly decreased cardiac index,
      heart rate, and HVPG. The magnitude of changes in HVPG observed between the basal
      and after drugs administration was greater in patients receiving carvedilol than
      in those receiving propranolol plus isosorbide-5-mononitrate (-18.6 +/- 3.6%vs
      10.1 +/- 3.6%, p < 0.05). Hepatic blood flow increased following carvedilol
      administration but remained unchanged in patients receiving propranolol plus
      isosorbide-5-mononitrate. The magnitude of decrease in mean arterial pressure
      (MAP) did not differ between the two groups of patients. CONCLUSION: In our
      patients with viral cirrhosis, carvedilol is more effective than propranolol plus
      isosorbide-5-mononitrate in the reduction of HVPG. Carvedilol administration
      causes an increase in hepatic blood flow, but its systemic effects were similar
      to those of propranolol plus isosorbide-5-mononitrate.

PMID- 15447756
TI  - The natural history of portal hypertensive gastropathy in patients with liver
      cirrhosis and mild portal hypertension.
AB  - BACKGROUND: Portal hypertensive gastropathy is a potential cause of bleeding in
      patients with liver cirrhosis. Studies on its natural history have often included
      patients submitted to endoscopic or pharmacological treatment for portal
      hypertension. PATIENTS AND METHODS: A total of 222 cirrhotic patients with mild
      degree of portal hypertension (i.e., with no or small varices at entry, without
      previous gastrointestinal bleeding and medical, endoscopic, or angiographic
      treatment) were followed up with upper endoscopy every 12 months for 47 +/- 28
      months. RESULTS: Upon enrollment 48 patients presented portal hypertensive
      gastropathy (43 mild and 5 severe) and the presence of esophageal varices was the
      only independent predictor of the presence of this gastric lesion at multivariate
      analysis. The incidence of portal hypertensive gastropathy was 3.0% (1.1-4.9%) at
      1 yr and 24% (18.1-29.9%) at 3 yr, while the progression was 3% (1-6.9%) at 1 yr
      and 14% (4.2-23.8%) at 3 yr. The presence of esophageal varices and the Child
      Pugh class B or C at enrollment were predictive of the incidence of portal
      hypertensive gastropathy, while only Child-Pugh class B or C was correlated with
      the progression from mild to severe, at multivariate analysis. During follow-up
      16 patients bled from portal hypertensive gastropathy (9 acutely and 7
      chronically) and one patient died of exsanguination from this lesion.
      CONCLUSIONS: The natural history of portal hypertensive gastropathy is
      significantly influenced by the severity of liver disease and severity of portal
      hypertension. Acute bleeding from portal hypertensive gastropathy is infrequent
      but may be severe.

PMID- 15447757
TI  - Assessment of thrombin-activatable fibrinolysis inhibitor (TAFI) plasma levels in
      inflammatory bowel diseases.
AB  - OBJECTIVES: Hypofibrinolysis has been proposed as a possible mechanism underlying
      the known risk of thrombosis observed in patients with inflammatory bowel
      diseases (IBD). Thrombin-activatable fibrinolysis inhibitor (TAFI) is a recently
      described inhibitor of fibrinolysis. Increased TAFI plasma levels are associated
      with a risk for venous thrombosis. The objective was to evaluate TAFI plasma
      levels and their possible correlations with clinical features and acute-phase
      reactants in IBD patients. METHODS: Eighty-one IBD patients (47 Crohn's disease
      and 34 ulcerative colitis) and 81 sex- and age-matched healthy controls were
      enrolled in the study; moreover, we studied 30 inflammatory controls (13 Reiter's
      syndrome, 4 Behcet's syndrome, and 13 patients with newly diagnosed celiac
      disease). TAFI plasma levels were assessed by means of a commercially available
      ELISA kit. Erythrocytes sedimentation rate, C-reactive protein, and alpha1-acid
      glycoprotein were measured as acute-phase reactants. Statistical analysis was
      performed by means of nonparametric tests and Fisher's exact test and chi(2) test
      for independence. RESULTS: Median TAFI plasma levels were significantly higher in
      IBD patients (116.0%, range: 39.0-232.0%) and in inflammatory controls (176.0%,
      50.0-435.0%) than in healthy controls (99.0%, 40.0-170.0%) (p< or = 0.05 and p<
      or = 0.001, respectively). TAFI plasma levels higher than the 95th percentile of
      control values were significantly more frequent in IBD patients (19.7%) and in
      inflammatory controls (53.3%) than in healthy controls (4.9%) (p< or = 0.008 and
      p< or = 0.0001, respectively) and more frequent in clinically active IBD than in
      clinically quiescent IBD (31.4%vs 10.9%, p< or = 0.03). Finally, in IBD,
      significant correlations were observed between TAFI plasma levels and
      erythrocytes sedimentation rate (p< or = 0.02), C-reactive protein (p< or =
      0.001), and alpha1-acid glycoprotein (p< or = 0.05). CONCLUSIONS: TAFI plasma
      levels are increased in IBD patients and correlate with acute-phase reactants.
      Increased TAFI plasma levels might contribute to the prothrombotic state observed
      in IBD through the induction of hypofibrinolysis.

PMID- 15447758
TI  - Thromboembolism--an important manifestation of inflammatory bowel disease.
AB  - Thromboembolism is an extraintestinal manifestation and an important cause of
      mortality in inflammatory bowel disease (IBD). The risk of thromboembolism
      appears to be multifactorial and related to mucosal inflammatory activity in most
      patients. Various laboratory markers such as thrombin activatable fibrinolysis
      inhibitor (TAFI) levels have been linked with thrombophilia in IBD but no single
      laboratory marker has emerged with sufficient predictive value to identify
      patients at particular risk. Prospective multifactorial analyses will be
      required; in the interim, clinicians must be vigilant and address common risk
      factors for thromboembolism in all patients with IBD.

PMID- 15447759
TI  - The month of birth is linked to the risk of Crohn's disease in the Israeli
      population.
AB  - OBJECTIVE: The main objective is to study whether the month of birth is
      associated with the development of Crohn's disease (CD) in the Israeli Jewish
      population. BACKGROUND: It was suggested that perinatal exposure to infectious
      agents may have a role in the pathogenesis of CD. Due to the seasonal nature of
      some infections, a linkage between birth dates and a risk to develop CD would
      support such a hypothesis. Previous studies that addressed this question were
      conducted in Europe and differed in their findings. METHODS: Birth dates of 844
      Jewish ulcerative colitis (UC) and CD patients from three medical centers
      representing the north, central, and the south of Israel were compared with the
      monthly rates of birth during the same period of time. The standard incidence
      ratio was used to define the risk to develop either disease according to the
      month of birth. The Score method was used for the evaluation of seasonality
      trends. RESULTS: Birth during the winter period in Israel was associated with
      increased risk to develop CD, whereas birth during the spring was associated with
      a reduced risk. The Score method for seasonality showed a significant peak during
      winter time in these patients (z = 2.02, p= 0.021). No such seasonal variation
      was noted for UC patients. CONCLUSIONS: A seasonal pattern was observed in the
      risk to develop CD but not UC. The findings may support the involvement of
      environmental factors in the pathogenesis of CD.

PMID- 15447760
TI  - Bowel wall thickness at abdominal ultrasound and the one-year-risk of surgery in
      patients with Crohn's disease.
AB  - OBJECTIVES: Abdominal ultrasound can assess the extent and localization of
      Crohn's disease, and an increased bowel wall thickness is the most common
      finding. Our aim was to correlate bowel wall thickness at ultrasound, with the
      risk of short-term surgical outcome in patients with Crohn's disease. MATERIALS
      AND METHODS: From 1997 to 2000 we performed ultrasound in 174 consecutive
      patients with Crohn's disease. Surgical operations were recorded over a 1-yr
      follow-up. Logistic regression analysis was performed to identify clinical and
      ultrasound risk factors for surgery. RESULTS: Fifty-two patients underwent
      surgery within 1 yr. Indication for surgery was strictures in most of the cases.
      Median bowel wall thickness was higher in patients with surgery (8 mm) than those
      without surgery (6 mm) (p < 0.0001). A receiver operating characteristic (ROC)
      curve was constructed taking into account bowel wall thickness for selecting
      patients with a high risk of surgery. The optimized cut-off for equally important
      sensitivity and specificity was calculated at 7.008 mm. The binary regression
      analysis showed that CDAI > 150, absence of previous surgery, stricturing
      penetrating pattern, the presence of intestinal complications, and intestinal
      wall thickness >7 mm were associated with an increased risk of surgery. Patients
      with intestinal wall thickness >7 mm at ultrasound had the highest risk (OR:
      19.521, 95% CI: 5.362-71.065). CONCLUSIONS: Data suggest that bowel wall
      thickness >7 mm at ultrasound is a risk factor for intestinal resection over a
      short period of time. Routine use of abdominal ultrasound during evaluation of
      patients with Crohn's disease may identify a subgroup that is at high risk for
      surgery. (Am J Gastroenterol 2004;99:1-7)

PMID- 15447761
TI  - An open-label study of the human anti-TNF monoclonal antibody adalimumab in
      subjects with prior loss of response or intolerance to infliximab for Crohn's
      disease.
AB  - BACKGROUND: We assessed the tolerability and clinical benefit of adalimumab, a
      human antibody to tumor necrosis factor (TNF), in patients with Crohn's disease
      who had previously received and responded to the chimeric anti-TNF antibody
      infliximab, but who no longer had a sustained response and/or tolerance to
      infliximab. METHODS: A total of 24 patients with Crohn's disease who had lost
      responsiveness or developed intolerance (acute or delayed infusion reactions) to
      infliximab were enrolled in a 12-wk uncontrolled trial and treated with
      subcutaneous adalimumab 80 mg at week 0 and then 40 mg every other week starting
      at week 2. After week 4, the dose could be escalated to 40 mg weekly in patients
      who did not achieve clinical remission, complete fistula closure, and complete
      steroid withdrawal. Outcome measures included the ability to tolerate adalimumab
      and clinical remission (defined as a Crohn's disease activity index (CDAI) score
      < or =150 points) and clinical response (defined as a decrease in the CDAI) > or
      =100 points) in patients who had a baseline CDAI score > or =220. RESULTS: None
      of the patients experienced acute or delayed hypersensitivity reactions during
      treatment with adalimumab (including 14 who previously experienced treatment
      limiting acute hypersensitivity reactions and 6 who previously experienced
      delayed hypersensitivity reactions with infliximab). Of 17 patients with baseline
      CDAI scores > or =220: clinical remission occurred at weeks 4 and 12 in 2 (12%)
      and 5 (29%), respectively; and clinical response occurred in 7 (41%) and 10
      (59%), respectively. Nineteen patients (79%) escalated their dose during weeks 4
      6. CONCLUSIONS: Adalimumab is well tolerated and appears to be a clinically
      beneficial option for patients with Crohn's disease who have previously lost
      their response to, or cannot tolerate infliximab.

PMID- 15447762
TI  - Acupuncture has a placebo effect on rectal perception but not on distensibility
      and spatial summation: a study in health and IBS.
AB  - BACKGROUND: Recent data suggest that acupuncture has effects on gut physiology
      and perception. Spatial summation is a central mechanism of perception and
      describes the phenomenon that thresholds for perception are lower if more
      receptors are stimulated. OBJECTIVES: We assessed perception thresholds for
      rectal distension and cutaneous referral of symptoms, while inflating one or two
      rectal balloons and the effect of both electro-acupuncture and placebo
      acupuncture on rectal distensibility, perception, and spatial summation. METHODS:
      A tube with two barostat balloons was placed in the rectum of 12 healthy subjects
      and nine irritable bowel syndrome (IBS) patients with rectal symptoms. Volume
      controlled stepwise distension of the distal balloon only or both balloons was
      performed first as a control, and thereafter with simultaneous placebo- or
      electro-acupuncture in dermatomes S3 and S4. A symptom questionnaire and anatomic
      questionnaire was completed during each distension. RESULTS: Rectal elastance
      increased from 42.0 +/- 19.6 log mmHg/ml during one-balloon distension to 59.6 +/
      33.1 log mmHg/ml during two-balloon distension (p < 0.05) in healthy subjects,
      and from 48.8 +/- 14.4 log mmHg/ml (one balloon) to 77.6 +/- 24.2 log mmHg/ml (p
      < 0.001) in patients with IBS. Electro-acupuncture had no effect on rectal
      sensation, elastance, and cutaneous referral when compared to placebo
      acupuncture. However, acupuncture (both electro- and placebo-) increased volume
      thresholds for sensation compared to control experiments, while objective
      parameters like rectal tone and elastance were unaltered. CONCLUSION: Acupuncture
      has a placebo effect on rectal perception but has no effect on rectal
      distensibility and visceral referral. Spatial summation affected both rectum
      distensibility and perception, but was also not altered by acupuncture.

PMID- 15447763
TI  - Patients with chest pain and occult gastroesophageal reflux demonstrate visceral
      pain hypersensitivity which may be partially responsive to acid suppression.
AB  - OBJECTIVES: Mechanisms of chest pain in gastroesophageal reflux disease (GERD)
      are poorly understood. The recent demonstration in healthy subjects that lower
      esophageal acid exposure induces pain hypersensitivity within the non-acid
      exposed upper esophagus (secondary allodynia) raises the possibility that an
      increase in spinal neuronal excitability (i.e., central sensitization)
      contributes to chest pain in GERD. The aim of this study was to determine whether
      in patients with unexplained chest pain, acid reflux contributes to esophageal
      pain hypersensitivity. METHODS: In 14 patients with chest pain and GERD and 8
      healthy volunteers, electrical pain thresholds (PT) were recorded from the upper
      esophagus before, and then repeatedly for 90 min after either hydrochloric acid
      (0.15 M) or saline (0.15 M) infusion into the lower esophagus. Six patients
      underwent a repeat study after 6 wk of high-dose proton pump inhibitor (PPI)
      therapy. RESULTS: GERD patients had lower resting upper esophageal PT than in
      healthy subjects (40.8 +/- 9 mA and 70.4 +/- 11 mA, respectively; p= 0.018). Acid
      infusion reduced PT in the non-acid-exposed upper esophagus in healthy subjects,
      but not in the patients (area under curve [AUC] - 304 +/- 333 and 786 +/- 464; p=
      0.03, respectively). Following PPI therapy, resting PT increased (34.65 +/- 13.4
      to 40.5 +/- 12.5 mA; p= 0.03), and a reduction in PT now occurred in acid
      infusion (AUC - 369 +/- 321; p= 0.03). CONCLUSIONS: Patients with unexplained
      chest pain and occult GERD have esophageal pain hypersensitivity that is PPI
      responsive. The increase in resting PT and secondary allodynia only following PPI
      therapy suggests that pain hypersensitivity in these GERD patients may partially
      be the result of central sensitization.

PMID- 15447764
TI  - Is diverticulosis associated with colorectal neoplasia? A cross-sectional
      colonoscopic study.
AB  - OBJECTIVE: To determine the relationship between distal diverticulosis and risk
      for colorectal neoplasia. METHODS: Patients undergoing first-time colonoscopy for
      any indication were eligible if they had no prior polypectomy, colonic resection,
      or inflammatory bowel disease. Patients completed a survey about risk factors for
      colorectal cancer (CRC) prior to colonoscopy. Endoscopists, blinded to study
      objective and survey results, recorded the size, extent (none, few, or many), and
      location of diverticuli and polyps. RESULTS: The 502 participants were 67% male
      with a mean age of 58.6 yr. Twenty-three percent had extensive distal
      diverticulosis (EDD), 36% had > or =1 adenoma, and 14% had advanced neoplasia.
      Overall comparison of those with EDD versus few or no diverticuli revealed no
      differences in the risks of any neoplasia or advanced neoplasia, either distally
      (26.7%vs 25.4%; 12.9%vs 8.8%, respectively) or proximally (25%vs 18.4%; 6.0%vs
      4.9%). Compared to women with few or no distal diverticuli, however, women with
      EDD were more likely to have any neoplasia and advanced neoplasia, both distally
      (34.6%vs 16.3%; p= 0.03, and 23.1%vs 5.7%; p= 0.003) and proximally (30.8%vs
      14.9%; p= 0.049, and 11.5%vs 4.3%, p= 0.13). Adjustment for age did not affect
      results for advanced distal neoplasia (OR = 3.92; CI: 1.18-13); however,
      adjustment for the presence of a distal neoplasm eliminated the increased risk of
      proximal neoplasia associated with EDD (OR = 1.31; CI: 0.43-4.02). CONCLUSION: In
      this study, women with EDD were more likely to have advanced distal neoplasia.
      The presence of distal neoplasia in women with EDD accounted for their increased
      risk of proximal neoplasia. Distal diverticulosis was not independently
      associated with proximal neoplasia in men or women.

PMID- 15447765
TI  - Phenotypic characteristics and risk of cancer development in hyperplastic
      polyposis: case series and literature review.
AB  - OBJECTIVES: Hyperplastic polyposis (HP) is a poorly understood condition. The aim
      of this study is to describe the phenotype and the risk of cancer in HP. METHODS:
      Patients with HP, as defined by the WHO International Classification, were
      identified through the University of Utah and the Huntsman Cancer Institute
      databases. Family history was retrieved when possible. RESULTS: Fifteen patients
      were identified (10 M, 5 F) with a mean age at diagnosis of 52.6 +/- 16.4 yr (18
      71). Sixty-five colonoscopies were performed (2-11 per person). A median of 90
      polyps (16-210) per person and 15 polyps (range, 0-100) per procedure were
      reported. The median follow-up was 33 months (3-133); no cancer occurred during
      this period. Polyps were more frequent in the distal than the proximal colon
      (74%vs 26%; p < 0.001). The median polyp size was 4 mm (1-40 mm). Fifty-one
      hyperplastic polyps >10 mm were identified in 10 patients (38 proximal, 13
      distal; p= 0.089). Forty-eight adenomas were found in 11 patients and were
      uniformly distributed. Serrated adenomas (n = 3) were found in one patient. A
      unique patient had 20 large hyperplastic polyps, 24 adenomas, 3 serrated
      adenomas, and 118 hyperplastic polyps. None of the patients had a first-degree
      relative with colon cancer. CONCLUSIONS: In HP, hyperplastic polyps are more
      frequently distal colonic, and vary greatly in size and number. Most patients
      also develop adenomas that are distributed throughout the colon. No cancers
      developed within 3 yr of follow-up. Colonoscopic surveillance at intervals of 1-3
      yr, depending upon the number and size of both adenomatous and hyperplastic
      polyps, appears prudent.

PMID- 15447766
TI  - Risk factors for advanced disease in colorectal cancer.
AB  - OBJECTIVES: The goal of this study was to identify predictors of presenting with
      late-stage colorectal cancer with a focus on potentially modifiable factors.
      METHODS: This was a multicenter, case-based study of patients with colorectal
      cancer. Detailed information about the cancer was abstracted from the tumor
      registries, pathology reports, and medical records. The remaining information was
      obtained by telephone interview. Inclusion criteria were age 40-85 yr with a
      first diagnosis of histologically proven colorectal cancer between July 1, 1997
      and January 1, 2001. Simple contingency table methods were used to examine the
      relationship between potential risk factors for early versus advanced-stage
      disease. Logistic regression was performed to simultaneously control for
      potential confounding factors. RESULTS: There was complete information for 549
      respondents. Approximately, 43% of the sample presented with late-stage
      colorectal cancer. In univariate analysis, lacking a usual source of health care
      (doctor's office or clinic), no participation in any colorectal cancer screening
      test in the prior 10 yr, symptoms of blood in stool, and unexplained weight loss
      were associated with late-stage colorectal cancer. In the logistic regression
      model, only lacking a usual source of healthcare and unexplained weight loss were
      associated with late-stage colorectal cancer with odds ratios (95% confidence
      intervals) of 0.4 (0.2-0.6) and 1.9 (1.2-3.0), respectively. CONCLUSIONS: These
      results suggest that system changes in the VA health-care system that increase
      access to and improve utilization of primary care may reduce presentation with
      late-stage colorectal cancer and thus, reduce mortality from colorectal cancer in
      veterans.

PMID- 15447767
TI  - Low prevalence of loss of heterozygosity and SMAD4 mutations in sporadic and
      familial juvenile polyposis syndrome-associated juvenile polyps.
AB  - BACKGROUND: Juvenile polyps (JP) may develop sporadically or may be associated
      with the familial juvenile polyposis syndrome (FJPS). In FJPS, the epithelium is
      susceptible to dysplasia and, ultimately adenocarcinoma. However, the mechanisms
      involved in this transformation are unknown. Since the epithelium in colorectal
      carcinogenesis undergoes a stepwise genetic progression, the purpose of this
      study was to determine if loss of heterozygosity (LOH) abnormalities can aid in
      the differentiation between sporadic and FJPS-associated polyps. DESIGN: Ninety
      one routinely-processed JP from three groups of patients were evaluated for this
      study. Group 1 included 39 polyps from 39 patients with a single JP and no
      personal or family history of FJPS; group 2 consisted of 24 polyps from 15
      patients with 2-5 JP and no history of FJPS; and group 3 included 29 polyps from
      22 patients with > or =5 polyps either with (7) or without (15) a family history
      of FJPS. Epithelium from typical, atypical, and overtly dysplastic polyps, when
      present (2 cases in group 3 only), were evaluated separately by microdissection
      and PCR analysis for LOH of APC, p53, 3p, 9p, and mutations in exon 9 of the
      SMAD4 gene. RESULTS: SMAD4 mutations were observed in 3 polyps from 2 patients in
      group 3 (10% of informative cases; p < 0.05 vs group 1), but not in any of the
      polyps from the other two groups. Overall, LOH of APC, p53, 3p, and 9p were
      detected in 1%, 15%, 10%, and 4% of JPs, but no differences were observed between
      the three clinical groups. Two polyps, both in group 3, with definite dysplasia
      did not show any genetic alterations. The morphologic appearance of the polyps
      was not a reliable feature in helping to differentiate sporadic from FJPS
      associated polyps. CONCLUSIONS: LOH of APC, p53, 3p, and 9p may not be involved
      in the carcinogenic pathway of FJPS-associated polyps. SMAD4 gene mutations show
      a low sensitivity but a high specificity for FJPS.

PMID- 15447768
TI  - Significance of HBV DNA levels in liver histology of HBeAg and Anti-HBe positive
      patients with chronic hepatitis B.
AB  - OBJECTIVE: To determine the relationship between hepatitis B virus (HBV) DNA
      levels and total histologic activity index (HAI), necroinflammation (HAI-NI), and
      fibrosis (HAI-F) scores. PATIENTS AND METHODS: Liver histology and HBV DNA levels
      were determined in 94 patients with chronic hepatitis B. RESULTS: There was no
      association between HBV DNA levels and liver histology in hepatitis-B-e antigen
      positive patients (n = 43). In anti-HBe-positive patients (n = 51), HBV DNA
      levels correlated positively with HAI-NI (r = 0.31, p= 0.014) and HAI-F (r =
      0.33, p= 0.017) scores. Though the majority of anti-HBe-positive patients with
      HBV DNA levels <10(5) copies/ml had mild necroinflammation and no fibrosis, 14.3%
      had established fibrosis. Anti-HBe-positive patients with core promoter mutations
      had a poorer histology compared to those without. There was no difference in the
      histology between anti-HBe-positive patients with and without precore mutations.
      Alanine aminotransferase (ALT) level correlated positively with HAI-NI score.
      Patients with persistently normal ALT levels had a significantly lower median HAI
      NI score compared to patients with either persistently or intermittently elevated
      ALT levels. CONCLUSIONS: In anti-HBe-positive patients, though HBV DNA level
      <10(5) copies/ml was associated with better histology, 14.3% patients had
      established fibrosis. Further studies to define a better cut-off HBV DNA level to
      differentiate low- and high-risk patients for disease progression are required.

PMID- 15447769
TI  - Pancreatic mass lesions associated with raised concentration of IgG4.
AB  - Autoimmune pancreatitis (AIP) is a recognized benign disease characterized by
      irregular narrowing of the pancreatic duct, swelling of parenchyma,
      lymphoplasmacytic infiltration and fibrosis, and a favorable response to
      corticosteroid treatment. In this condition, the whole pancreas is diffusely
      affected. Recently, however, a few cases with locally affected lesions were
      reported, with some of them showing features similar to cancer. We reviewed 138
      patients with pancreatic mass lesion, of which 17 were not initially diagnosed
      despite examinations. Serum IgG4 levels were elevated in seven of them. Their
      biopsy specimens had a similar appearance to those of AIP. We considered that
      they should be diagnosed as AIP or conditions related to AIP. Among the 10
      patients without elevated IgG4, 4 patients were diagnosed as pancreatic cancer
      after follow-up, 1 presented with an islet cell tumor, 1 presented AIP with
      sclerosing cholangitis, and the other 4 had chronic pancreatitis.

PMID- 15447770
TI  - Association of Helicobacter pylori infection with Shigella gastroenteritis in
      young children.
AB  - OBJECTIVE: Helicobacter pylori infection is acquired mainly in early childhood.
      Much is unknown about the mode of transmission. The organism can be cultivated
      from cathartic stools and vomitus and is potentially transmissible during
      episodes of gastrointestinal tract illness. Because Shigella and Salmonella are
      common pathogens in enteric infections in children, we examined the association
      of H. pylori with Shigella and Salmonella infections in pediatric patients.
      METHODS: The study population included consecutive children aged 2-72 months
      hospitalized with acute gastroenteritis who had culture-proven shigellosis (N =
      78) or salmonellosis (N = 76). Sixty-five healthy similarly aged children with
      culture-negative stools served as controls. Parents of cases were queried for
      personal and family characteristics and socioeconomic indicators. The stool
      specimens from all participants were tested for H. pylori antigen. RESULTS: On
      univariate analysis, Shigella gastroenteritis was significantly associated with
      H. pylori positivity (odds ratio, OR: 3.5, 95% confidence interval (CI): 1.5-8.8,
      p= 0.004) compared to controls. This association remained significant even after
      adjusting for living conditions, father's occupation, and father's education (OR
      = 3.38, 95% CI: 1.39-8.22, p= 0.007). Salmonella gastroenteritis was not
      associated with H. pylori positivity (OR = 1.1; 95% CI: 0.4-3.0, p= 0.8).
      CONCLUSION: H. pylori infection in young children is associated with Shigella
      gastroenteritis. This association warrants further investigation.

PMID- 15447771
TI  - Dietary fructose and gastrointestinal symptoms: a review.
AB  - It has been proposed that fructose may cause or aggravate symptoms in patients
      with functional gastrointestinal disorders. Fructose is commonly used to sweeten
      processed foods, and the prevalence of incomplete fructose absorption (25 g, 10%)
      in healthy subjects is as high as 50%. The only controlled study that has been
      performed did not demonstrate a higher prevalence of fructose-induced
      gastrointestinal symptoms or incomplete fructose absorption in patients with
      functional gastrointestinal disorders. The amount and concentration of fructose
      used to evaluate absorption by breath testing has varied among studies. Moreover,
      dietary sources of fructose usually contain glucose, which increases fructose
      absorption in healthy subjects. Thus, breath testing with fructose alone may not
      reflect fructose ingestion under normal circumstances. Given these limitations,
      we suggest that a practical, empirical approach to testing in patients with
      suspected incomplete fructose absorption is to restrict fructose ingestion.
      Additional controlled studies are needed to clarify the relation between
      incomplete fructose absorption and symptoms, assess the effects of co-ingestion
      of other sugars on fructose absorption, and evaluate the effects of eliminating
      sugars from the diet on gastrointestinal symptoms.

PMID- 15447772
TI  - Pooled analysis of the efficacy and safety of self-expanding metal stenting in
      malignant colorectal obstruction.
AB  - BACKGROUND: Self-expanding metal stents have been used in the management of
      colorectal obstruction as an alternative to emergency surgery. Our aim was to
      systematically review the efficacy and safety of these stents in the setting of
      malignant colorectal obstruction. METHODS: Both English and foreign language
      reports were identified from Medline, Embase, Cancerlit, Science Citation Index,
      Cochrane Library, and proceedings of relevant meetings. Data were collected on
      technical success, clinical success, and safety parameters. RESULTS: Fifty-four
      studies reported the use of stents in a total of 1,198 patients. The median
      technical and clinical success rates were 94% (i.q.r. 90-100) and 91% (i.q.r. 84
      94), respectively. The clinical success when used as a bridge to surgery was
      71.7%. Major complications related to stent placement included perforation
      (3.76%), stent migration (11.81%), and reobstruction (7.34%). Factors related to
      an increased complication risk were identified. Stent-related mortality was
      0.58%. Limited available data suggest that this approach may be cost effective in
      the preoperative setting. CONCLUSION: Placement of self-expanding metal stents is
      an effective and safe definitive procedure in the palliation of malignant
      colorectal obstruction. In operable patients, it provides a useful option to
      avoid colostomy, by facilitating safer single-stage surgery.

PMID- 15447773
TI  - Isolated visceral small artery fibromuscular hyperplasia-induced ischemic colitis
      mimicking inflammatory bowel disease.
AB  - A unique case of fibromuscular hyperplasia (FMH) of the visceral vasculature is
      presented. A 31-yr-old patient presented with a chronic colitis initially
      diagnosed as ulcerative colitis 1 yr earlier. On presentation, the endoscopic
      appearance showed deep linear ulcerations and cobblestoning and was more
      consistent with Crohn's disease. Biopsies of the area, however, suggested an
      ischemic etiology. The patient failed to respond to local 5ASA and prednisone
      therapy and progression of the disease led to a left hemicolectomy. A diagnosis
      of a small vessel fibromuscular arteriopathy was made on the resected specimen.
      This is the first case presentation of FMH mimicking inflammatory bowel disease.
      The lack of any systemic involvement of FMH with isolated small vessel disease
      has never been reported and serves as an index case of which clinicians should be
      aware. The literature is reviewed and the possible implications are discussed.

PMID- 15447774
TI  - Refractory bleeding after endoscopic sphincterotomy: a new indication for
      recombinant factor VII therapy?
AB  - The therapeutic approach in post-ERCP bleeding depends on the severity of the
      episode. In most instances early bleeding is self-limited, but when it is severe
      enough endoscopic injection of epinephrine (EP) is the usual treatment.
      Nevertheless, in some cases bleeding relapses, whereas in between 5% and 10% of
      patients the refractoriness to endoscopic management may even be fatal and other
      therapeutic alternatives would be needed. Otherwise, in a small subgroup of cases
      the bleeding becomes massive, the vision is obscured, and the injection may be
      very difficult in a situation of hemodynamic instability. We here report a case
      of refractory post-endoscopic sphincterotomy (ES) bleeding in a patient without
      preexisting coagulopathy, successfully treated with a single injection of rFVII.
      This novel experience suggests that rFVIIa, besides its actual high costs, might
      be useful and safe as a second-line, noninvasive, therapeutic tool in selected
      cases of massive, or refractory, post-ES bleeding.

PMID- 15447775
TI  - Development of fistulae in ileo-anal pouch does not necessarily indicate Crohn's
      disease.

PMID- 15447777
TI  - Crohn's disease recurrence in small bowel transplant.

PMID- 15447778
TI  - Short questionnaire based on IBDQ.

PMID- 15447780
TI  - Concurrence of primary biliary cirrhosis and antiphospholipid antibody syndrome.

PMID- 15447781
TI  - The management of patients who have "failed" antireflux surgery.

PMID- 15447785
TI  - Mental health in prison populations. A review--with special emphasis on a study
      of Danish prisoners on remand.
AB  - OBJECTIVE: To review the literature on mental health and psychiatric morbidity in
      prison populations and relate findings to a Danish study on remand prisoners.
      METHOD: The literature is reviewed and subdivided in the following section:
      validity of psychometrics in prison populations, prevalence of psychiatric
      disorders prior to imprisonment, incidence of psychiatric disorders during
      imprisonment, psychopathy related to psychiatric comorbidity, dependence
      syndromes with special emphasis on different administrations of heroin use (smoke
      vs. injection). The results are compared with a longitudinal Danish study on
      remand prisoners in either solitary confinement (SC) or non-SC. RESULTS: Many
      factors must be taken into consideration when dealing with prisoners and mental
      health, e.g. international differences, the prison setting, demographics and
      methodological issues. The prison populations in general are increasing
      worldwide. Psychometrics may perform differently in prison populations compared
      with general populations with the General Health Questionnaire-28 having a low
      validity in remand prisoners. Psychiatric morbidity including schizophrenia is
      higher and perhaps increasing in prison populations compared with general
      populations with dependence syndromes being the most frequent disorders. The
      early phase of imprisonment is a vulnerable period with a moderately high
      incidence of adjustment disorders and twice the incidence in SC compared with non
      SC. Prevalence of psychopathy is lower in European than North American prisons.
      Medium to high scores of psychopathy is related to higher psychiatric
      comorbidity. Opioid dependence is the most frequent drug disorder with subjects
      using injection representing a more dysfunctional group than subjects using smoke
      administration. Many mentally ill prisoners remain undetected and undertreated.
      CONCLUSION: There is a growing population of mentally ill prisoners being
      insufficiently detected and treated.

PMID- 15447786
TI  - Low autocrine interferon beta production as a gene therapy approach for AIDS:
      Infusion of interferon beta-engineered lymphocytes in macaques chronically
      infected with SIVmac251.
AB  - BACKGROUND: The aim of this study was to evaluate gene therapy for AIDS based on
      the transduction of circulating lymphocytes with a retroviral vector giving low
      levels of constitutive macaque interferon beta production in macaques chronically
      infected with a pathogenic isolate of SIVmac251. RESULTS: Two groups of three
      animals infected for more than one year with a pathogenic primary isolate of
      SIVmac251 were included in this study. The macaques received three infusions of
      their own lymphocytes transduced ex vivo with the construct encoding macaque IFN
      beta (MaIFN-beta or with a vector carrying a version of the MaIFN-beta gene with
      a deletion preventing translation of the mRNA. Cellular or plasma viremia
      increased transiently following injection in most cases, regardless of the
      retroviral construct used. Transduced cells were detected only transiently after
      each infusion, among the peripheral blood mononuclear cells of all the animals,
      with copy numbers of 10 to 1000 per 106 peripheral mononuclear cells. CONCLUSION:
      Long-term follow-up indicated that the transitory presence of such a small number
      of cells producing such small amounts of MaIFN-beta did not prevent animals from
      the progressive decrease in CD4+ cell count typical of infection with simian
      immunodeficiency virus. These results reveal potential pitfalls for future
      developments of gene therapy strategies of HIV infection.

PMID- 15447787
TI  - A mathematical model for LH release in response to continuous and pulsatile
      exposure of gonadotrophs to GnRH.
AB  - In a previous study, a model was developed to investigate the release of
      luteinizing hormone (LH) from pituitary cells in response to a short pulse of
      gonadotropin-releasing hormone (GnRH). The model included: binding of GnRH to its
      receptor (R), dimerization and internalization of the hormone receptor complex,
      interaction with a G protein, production of inositol 1,4,5-trisphosphate (IP3),
      release of calcium from the endoplasmic reticulum (ER), entrance of calcium into
      the cytosol via voltage gated membrane channels, pumping of calcium out of the
      cytosol via membrane and ER pumps, and release of LH. The extended model,
      presented in this paper, also includes the following physiologically important
      phenomena: desensitization of calcium channels; internalization of the dimerized
      receptors and recycling of some of the internalized receptors; an increase in Gq
      concentration near the plasma membrane in response to receptor dimerization; and
      basal rates of synthesis and degradation of the receptors. With suitable choices
      of the parameters, good agreement with a variety of experimental data of the LH
      release pattern in response to pulses of various durations, repetition rates, and
      concentrations of GnRH were obtained. The mathematical model allows us to assess
      the effects of internalization and desensitization on the shapes and time courses
      of LH response curves.

PMID- 15447788
TI  - Neoadjuvant or adjuvant therapy for resectable esophageal cancer: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Carcinoma of the esophagus is an aggressive malignancy with an
      increasing incidence. Its virulence, in terms of symptoms and mortality,
      justifies a continued search for optimal therapy. The large and growing number of
      patients affected, the high mortality rates, the worldwide geographic variation
      in practice, and the large body of good quality research warrants a systematic
      review with meta-analysis. METHODS: A systematic review and meta-analysis
      investigating the impact of neoadjuvant or adjuvant therapy on resectable
      thoracic esophageal cancer to inform evidence-based practice was
      produced.MEDLINE, CANCERLIT, Cochrane Library, EMBASE, and abstracts from the
      American Society of Clinical Oncology and the American Society for Therapeutic
      Radiology and Oncology were searched for trial reports. Included were randomized
      trials or meta-analyses of neoadjuvant or adjuvant treatments compared with
      surgery alone or other treatments in patients with resectable thoracic esophageal
      cancer. Outcomes of interest were survival, adverse effects, and quality of life.
      Either one- or three-year mortality data were pooled and reported as relative
      risk ratios. RESULTS: Thirty-four randomized controlled trials and six meta
      analyses were obtained and grouped into 13 basic treatment approaches. Single
      randomized controlled trials detected no differences in mortality between
      treatments for the following comparisons:- Preoperative radiotherapy versus
      postoperative radiotherapy.- Preoperative and postoperative radiotherapy versus
      postoperative radiotherapy. Preoperative and postoperative radiotherapy was
      associated with a significantly higher mortality rate.- Postoperative
      chemotherapy versus postoperative radiotherapy.- Postoperative radiotherapy
      versus postoperative radiotherapy plus protein-bound polysaccharide versus
      chemoradiation versus chemoradiation plus protein-bound polysaccharide. Pooling
      one-year mortality detected no statistically significant differences in mortality
      between treatments for the following comparisons:- Preoperative radiotherapy
      compared with surgery alone (five randomized trials).- Postoperative radiotherapy
      compared with surgery alone (five randomized trials).- Preoperative chemotherapy
      versus surgery alone (six randomized trials).- Preoperative and postoperative
      chemotherapy versus surgery alone (two randomized trials).- Preoperative
      chemoradiation therapy versus surgery alone (six randomized trials). Single
      randomized controlled trials detected differences in mortality between treatments
      for the following comparison:- Preoperative hyperthermia and chemoradiotherapy
      versus preoperative chemoradiotherapy in favour of hyperthermia. Pooling three
      year mortality detected no statistically significant difference in mortality
      between treatments for the following comparison:- Postoperative chemotherapy
      compared with surgery alone (two randomized trials). Pooling three-year mortality
      detected statistically significant differences between treatments for the
      following comparisons:- Preoperative chemoradiation therapy versus surgery alone
      (six randomized trials) in favour of preoperative chemoradiation with surgery.-
      Preoperative chemotherapy compared with preoperative radiotherapy (one randomized
      trial) in favour of preoperative radiotherapy. CONCLUSION: For adult patients
      with resectable thoracic esophageal cancer for whom surgery is considered
      appropriate, surgery alone (i.e., without neoadjuvant or adjuvant therapy) is
      recommended as the standard practice.

PMID- 15447789
TI  - Ubiquitin is associated with the survival of ectopic stromal cells in
      endometriosis.
AB  - BACKGROUND: Endometriosis is a condition that affects women of reproductive age,
      where the glandular and/or stromal tissues from the eutopic endometrium implant
      in ectopic locations. It is well established that the survival of ectopic
      implants is due to lower levels of apoptosis, but no consensus exists as to which
      pathway/s this is mediated by. The ubiquitin protein shares a similar sequence
      homology to an anti-apoptotic protein called BAG-1 and is expressed in the normal
      endometrium. Currently, no studies have been conducted to determine ubiquitin
      expression and its possible anti-apoptotic effects in endometriosis. METHODS:
      Archived endometrial tissues from endometriosis patients and women undergoing
      laparoscopic diagnosis (controls) from January 2000 to July 2003 at Westmead
      Hospital were examined, where 14 cases of endometriosis and 55 controls were
      included in the study. RESULTS: Both the ubiquitin protein and apoptosis were
      expressed in both glandular and stromal cells throughout the menstrual cycle of
      the eutopic endometrium, in which ubiquitin exhibited a cyclic expression,
      reaching a peak in late proliferative phase. In contrast, ubiquitin was
      predominantly expressed in cells of stromal origin in endometriosis, was no
      longer regulated by a cyclic pattern and was associated with an aberrant level of
      cell survival. CONCLUSIONS: For the first time, this study shows that ubiquitin
      is expressed in endometriotic cells and may contribute to a reduced sensitivity
      of ectopic endometrial tissue to apoptosis. These findings also suggest that
      stromal cells contribute differentially to the development of ectopic endometrial
      tissue.

PMID- 15447790
TI  - Magnesium administration provokes motor unit survival, after sciatic nerve injury
      in neonatal rats.
AB  - BACKGROUND: We examined the time course of the functional alterations in two
      types of muscles following sciatic nerve crush in neonatal rats and the
      neuroprotective effect of Mg2+. METHODS: The nerve crush was performed on the 2nd
      postnatal day. MgSO4*7H2O was administered daily for two weeks. Animals were
      examined for the contractile properties and for the number of motor units of
      extensor digitorum longus and soleus muscles at three postnatal stages and
      adulthood. Four experimental groups were included in this study: i) controls, ii)
      axotomized rats, iii) magnesium treated controls and iv) axotomized and Mg2+
      treated rats. RESULTS: Axotomy resulted in 20% MU survival in EDL and 50% in
      soleus. In contrast, magnesium treatment resulted in a significant motor unit
      survival (40% survival in EDL and 80% in soleus). The neuroprotective effects of
      Mg2+ were evident immediately after the Mg2+-treatment. Immature EDL and soleus
      muscles were slow and fatigueable. Soleus gradually became fatigue resistant,
      whereas, after axotomy, soleus remained fatigueable up to adulthood. EDL
      gradually became fastcontracting. Tetanic contraction in axotomized EDL was just
      3,3% of the control side, compared to 15,2% in Mg2+-treated adult rats. The same
      parameter for axotomized soleus was 12% compared to 97% in Mg2+-treated adult
      rats. CONCLUSIONS: These results demonstrate that motoneuron death occurs mostly
      within two weeks of axotomy. Magnesium administration rescues motoneurons and
      increases the number of motor units surviving into adulthood. Fast and slow
      muscles respond differently to axotomy and to subsequent Mg2+ treatment in vivo.

PMID- 15447791
TI  - Neoadjuvant or adjuvant therapy for resectable esophageal cancer: a clinical
      practice guideline.
AB  - BACKGROUND: Carcinoma of the esophagus is an aggressive malignancy with an
      increasing incidence. Its virulence, in terms of symptoms and mortality,
      justifies a continued search for optimal therapy. A clinical practice guideline
      was developed based on a systematic review investigating neoadjuvant or adjuvant
      therapy on resectable thoracic esophageal cancer. METHODS: A systematic review
      with meta-analysis was developed and clinical recommendations were drafted.
      External review of the practice guideline report by practitioners in Ontario,
      Canada was obtained through a mailed survey, and incorporated. Final approval of
      the practice guideline was obtained from the Practice Guidelines Coordinating
      Committee. RESULTS: The systematic review was developed and recommendations were
      drafted, and the report was mailed to Ontario practitioners for external review.
      Ninety percent of respondents agreed with both the evidence summary and the draft
      recommendations, while only 69% approved of the draft recommendations as a
      practice guideline. Based on the external review, a revised document was created.
      The revised practice guideline was submitted to the Practice Guidelines
      Coordinating Committee for review. All 11 members of the PGCC returned ballots.
      Eight PGCC members approved the practice guideline report as written and three
      members approved the guideline conditional on specific concerns being addressed.
      After these recommended changes were made, the final practice guideline report
      was approved. CONCLUSION: In consideration of the systematic review, external
      review, and subsequent Practice Guidelines Coordinating Committee revision
      suggestions, and final approval, the Gastrointestinal Cancer Disease Site Group
      recommends the following:For adult patients with resectable thoracic esophageal
      cancer for whom surgery is considered appropriate, surgery alone (i.e., without
      neoadjuvant or adjuvant therapy) is recommended as the standard practice.

PMID- 15447792
TI  - Characterization of a new full length TMPRSS3 isoform and identification of
      mutant alleles responsible for nonsyndromic recessive deafness in Newfoundland
      and Pakistan.
AB  - BACKGROUND: Mutant alleles of TMPRSS3 are associated with nonsyndromic recessive
      deafness (DFNB8/B10). TMPRSS3 encodes a predicted secreted serine protease,
      although the deduced amino acid sequence has no signal peptide. In this study, we
      searched for mutant alleles of TMPRSS3 in families from Pakistan and Newfoundland
      with recessive deafness co-segregating with DFNB8/B10 linked haplotypes and also
      more thoroughly characterized the genomic structure of TMPRSS3. METHODS: We
      enrolled families segregating recessive hearing loss from Pakistan and
      Newfoundland. Microsatellite markers flanking the TMPRSS3 locus were used for
      linkage analysis. DNA samples from participating individuals were sequenced for
      TMPRSS3. The structure of TMPRSS3 was characterized bioinformatically and
      experimentally by sequencing novel cDNA clones of TMPRSS3. RESULTS: We identified
      mutations in TMPRSS3 in four Pakistani families with recessive, nonsyndromic
      congenital deafness. We also identified two recessive mutations, one of which is
      novel, of TMPRSS3 segregating in a six-generation extended family from
      Newfoundland. The spectrum of TMPRSS3 mutations is reviewed in the context of a
      genotype-phenotype correlation. Our study also revealed a longer isoform of
      TMPRSS3 with a hitherto unidentified exon encoding a signal peptide, which is
      expressed in several tissues. CONCLUSION: Mutations of TMPRSS3 contribute to
      hearing loss in many communities worldwide and account for 1.8% (8 of 449) of
      Pakistani families segregating congenital deafness as an autosomal recessive
      trait. The newly identified TMPRSS3 isoform e will be helpful in the functional
      characterization of the full length protein.

PMID- 15447794
TI  - Research and publication in respiratory care.

PMID- 15447795
TI  - Overview of respiratory care research.
AB  - Few health care workers are directly involved in conducting research, but all
      must be able to read and understand scientific reports in medical journals. They
      must be familiar with the basic concepts of research in order to practice as
      professionals. The most important skill is the ability to read and critically
      evaluate published reports. Health care administrators rely on the results of
      studies to help solve problems and make decisions about important subjects, such
      as cost containment, productivity assessment, and continuous quality improvement.
      Educators must stay current with new technology and its evidence base. Both
      administrators and educators must be familiar with basic research concepts in
      order to be informed consumers of research information. Research attempts to find
      answers using the scientific method. This report describes the steps in the
      scientific method, the overall plan for conducting scientific research, and some
      basic skills required to successfully conduct research.

PMID- 15447793
TI  - Prediction of DtxR regulon: identification of binding sites and operons
      controlled by Diphtheria toxin repressor in Corynebacterium diphtheriae.
AB  - BACKGROUND: The diphtheria toxin repressor, DtxR, of Corynebacterium diphtheriae
      has been shown to be an iron-activated transcription regulator that controls not
      only the expression of diphtheria toxin but also of iron uptake genes. This study
      aims to identify putative binding sites and operons controlled by DtxR to
      understand the role of DtxR in patho-physiology of Corynebacterium diphtheriae.
      RESULT: Positional Shannon relative entropy method was used to build the DtxR
      binding site recognition profile and the later was used to identify putative
      regulatory sites of DtxR within C. diphtheriae genome. In addition, DtxR
      regulated operons were also identified taking into account the predicted DtxR
      regulatory sites and genome annotation. Few of the predicted motifs were
      experimentally validated by electrophoretic mobility shift assay. The analysis
      identifies motifs upstream to the novel iron-regulated genes that code for
      Formamidopyrimidine-DNA glycosylase (FpG), an enzyme involved in DNA-repair and
      starvation inducible DNA-binding protein (Dps) which is involved in iron storage
      and oxidative stress defense. In addition, we have found the DtxR motifs upstream
      to the genes that code for sortase which catalyzes anchoring of host-interacting
      proteins to the cell wall of pathogenic bacteria and the proteins of secretory
      system which could be involved in translocation of various iron-regulated
      virulence factors including diphtheria toxin. CONCLUSIONS: We have used an in
      silico approach to identify the putative binding sites and genes controlled by
      DtxR in Corynebacterium diphtheriae. Our analysis shows that DtxR could provide a
      molecular link between Fe+2-induced Fenton's reaction and protection of DNA from
      oxidative damage. DtxR-regulated Dps prevents lethal combination of Fe+2 and H2O2
      and also protects DNA by nonspecific DNA-binding. In addition DtxR could play an
      important role in host interaction and virulence by regulating the levels of
      sortase, a potential vaccine candidate and proteins of secretory system.

PMID- 15447796
TI  - Device and equipment evaluations.
AB  - Device evaluation, which is an essential skill set for the respiratory therapist,
      ranges from comparing manufacturer's specifications to comprehensive device
      testing, either with patients or on the bench. Good device evaluations help guide
      decisions about device selection, procedure development, and risk and failure
      analysis. Poor evaluations cost time and money and fail to return value.
      Manufacturer's specifications alone are poor criteria for device selection,
      because of how and why those specifications are created and the potential gap
      between the manufacturer's test methods and the complexity of clinical
      situations. Proper clinical evaluation of devices with patients requires
      extensive preparation and resource expenditure, and clinical evaluations may not
      allow isolating key variables to determine specifics of device performance. In
      vitro testing, using models to simulate discrete components of device/patient
      interface, is less expensive and easier to conduct. This article discusses the
      process of experiment design and model development for device and equipment
      evaluations.

PMID- 15447797
TI  - The spectrum of respiratory care research: prospective clinical research.
AB  - Prospective clinical research is given the greatest weight in evidence-based
      clinical practice recommendations, and therefore has the greatest potential to
      change care and help the largest number of patients. This article briefly
      describes the history of government regulation of prospective clinical research,
      how a prospective clinical research project is developed, and how the researcher
      seeks project approval from the institutional review board. We also evaluate 2
      published studies with regard to ethical and regulatory matters that influenced
      the studies.

PMID- 15447798
TI  - Retrospective studies and chart reviews.
AB  - A retrospective study uses existing data that have been recorded for reasons
      other than research. A retrospective case series is the description of a group of
      cases with a new or unusual disease or treatment. With a case-control study,
      cases with and without the condition of interest are identified, and the degree
      of exposure to a possible risk factor is then retrospectively compared between
      the 2 groups. With a matched case-control study, control subjects are selected
      such that they resemble (match) the cases with regards to certain characteristics
      (eg, age, comorbidity, severity of disease). Retrospective study designs are
      generally considered inferior to prospective study designs. Therefore, a
      retrospective study design should never be used when a prospective design is
      feasible.

PMID- 15447799
TI  - Quality-assurance research: studying processes of care.
AB  - To conduct a successful research study, several criteria must be satisfied: the
      research question must be important (not only to the investigators but to
      clinicians and managers in other institutions); the research question must be
      answerable with the available resources; the investigators must be motivated and
      capable; and the research setting must be appropriate for the study (the
      institution must have a supportive culture and analytical resources, and the
      local institutional review board must approve the proposed study). Quality
      assurance (QA) research poses some special challenges and requirements. First,
      although QA studies should be hypothesis-driven, they are usually before-and
      after studies, rather than randomized controlled trials. Second, in before-and
      after studies the investigators must address and minimize several possible
      sources of bias that could confound the results. For example, the compared groups
      must be similar in important features that could affect development of the
      outcome(s) of interest, and clinical practices other than the practice change
      that is being tested during the study must be shown not to independently affect
      the outcome(s) of interest. We discuss several examples of QA studies, and we
      offer a checklist for the process of considering, designing, executing,
      presenting, and publishing a QA study.

PMID- 15447800
TI  - Surveys: an introduction.
AB  - Surveys are a valuable research tool for studying the knowledge, attitudes, and
      behavior of a study population. This article explores quantitative analyses of
      written questionnaires as instruments for survey research. Obtaining accurate and
      precise information from a survey requires minimizing the possibility of bias
      from inappropriate sampling or a flawed survey instrument, and this article
      describes strategies to minimize sampling bias by increasing response rates,
      comparing responders to nonresponders, and identifying the appropriate sampling
      population. It is crucial that the survey instrument be valid, meaning that it
      actually measures what the investigator intends it to measure. In developing a
      valid survey instrument, it can be useful to adapt survey instruments that were
      developed by other researchers and to conduct extensive pilot-testing of your
      survey instrument.

PMID- 15447801
TI  - Case reports in respiratory care.
AB  - The information in a case report should be viewed cautiously in terms of
      generalization beyond the reported example. Appropriately written and
      interpreted, however, a case report can be a valuable contribution to medical
      knowledge and educational for both author and reader. This article discusses the
      essential components of a case report, important issues of patient
      confidentiality, and how authorship should be determined. It then describes 10
      common pitfalls in case report writing. These are inexperience, insufficient
      documentation of the case, insufficient awareness of practice beyond one's own
      clinical setting, describing substandard care, illogical or unphysiologic
      intervention, poor focus of presentation and discussion, inappropriate manuscript
      format, poor writing, ineffective illustrations, and poor use of references. The
      article then presents 10 specific ways to avoid or deal with these pitfalls, with
      the aim of increasing the likelihood that a prospective author's manuscript will
      be accepted for publication. These ways include seeking appropriate assistance
      with writing, documenting the case as thoroughly as possible, and carefully
      justifying any new technique or intervention. Authors are urged to expend the
      time and effort required to prepare the manuscript properly, using the journal's
      guidelines and paying special attention to illustrations and references, and also
      to have the manuscript read by a local colleague before formal submission. After
      submission, authors should view the receipt of reviewers' comments and subsequent
      manuscript revision as necessary and positive steps toward successful
      publication.

PMID- 15447802
TI  - How to come up with a good research question: framing the hypothesis.
AB  - Having a questioning attitude is the fist step in the research process. Research
      begins with a question, which leads to a hypothesis. Questions abound in our
      daily clinical lives. Most quality research consists of comparisons. By carefully
      selecting a comparison group or condition, the quality of the research project
      can be improved. By including in the hypothesis the comparison group, the
      experiment can be focused and the analysis simplified. The best questions come
      from the investigator's subject of interest. When starting a research project,
      start small and choose an experienced mentor.

PMID- 15447803
TI  - Facilitating research projects in schools and clinical respiratory care
      departments.
AB  - As the profession of respiratory care evolves, greater demands are being placed
      on educators, managers, and practitioners as they encounter a mass of new
      literature and the latest technology. Respiratory care schools and clinical
      departments are under increasing pressure to prepare students and staff with the
      skills needed to efficiently and effectively consider the numerous primary
      research investigations, systematic reviews, consensus practice guidelines, and
      institutional continuous-quality-improvement data. A classroom and work
      environment that encourages openness and discussion and rewards inquiry is of
      fundamental importance. Cooperative efforts from school and workplace can provide
      both student and practitioner with courses on scientific methodology, journal
      clubs, and equipment seminars. A student body and clinical staff that receive
      foundational and ongoing education in empirical methodology will respond by
      assisting in the development and implementation of practice protocols, quality
      assurance programs, and clinical research. A school and workplace that embrace
      these attitudes and practices will provide an environment that enhances learning,
      stimulates professional development, and ultimately provides the most current and
      best care for its patients.

PMID- 15447804
TI  - How to write an abstract that will be accepted for presentation at a national
      meeting.
AB  - Preparation, submission, and presentation of an abstract are important facets of
      the research process, which benefit the investigator/author in several ways.
      Writing an abstract consists primarily of answering the questions, "Why did you
      start?" "What did you do?" "What did you find?" and "What does it mean?" A few
      practical steps in preparing to write the abstract can facilitate the process.
      This article discusses those steps and offers suggestions for writing each of an
      abstract's components (title, author list, introduction, methods, results, and
      conclusions); considers the advantages and disadvantages of incorporating a table
      or figure into the abstract; offers several general writing tips; and provides
      annotated examples of well-prepared abstracts: one from an original study, one
      from a method/device evaluation, and one from a case report.

PMID- 15447805
TI  - How to make an effective poster.
AB  - Poster presentations given at scientific meetings are widely used in medicine,
      nursing, and allied health professions to communicate research findings. A good
      poster presentation can be an effective way to share the results of your research
      with your peers, in a collegial and non-threatening atmosphere. Feedback received
      during a poster session can be invaluable in refining your research and preparing
      for publication in a peer reviewed journal. A typical poster presentation follows
      the same format as a scientific paper. Poster sections include a title banner,
      the abstract, introduction, method, results, discussion, conclusions, and tables
      and figures. Technical details of poster production include decisions on what
      materials and methods to use to print and display your poster, font size, whether
      to use a professional graphics department for production, and cost. Presentation
      of your research at a professional meeting can be a rewarding experience, and is
      a useful step toward publishing your research in a respected science journal.

PMID- 15447806
TI  - How to present, summarize, and defend your poster at the meeting.
AB  - For many people public speaking induces stress and fear, but with adequate
      planning, practice, and understanding of the "dos and don'ts" you can deliver
      presentations that will communicate your research clearly, succinctly, and with a
      professional and confident demeanor. This article provides a guide for the novice
      researcher to develop the skills to deliver several types of presentation and to
      minimize (and even make use of) the stress and fear. Planning and practice are
      the key to success.

PMID- 15447807
TI  - Anatomy of a research paper.
AB  - Writing, editing, and publishing the paper is the last step in the research
      process. The paper tells the story of the project from inception, through the
      data-collection process, statistical analysis, and discussion of the results.
      Novice authors often struggle with writing and often find themselves with either
      nothing on paper or a weighty version of random thoughts. The process of writing
      the paper should be analogous to the research process. This article describes and
      provides a template for the essential sections and features of a scientific
      report (structured abstract, introduction, hypothesis, methods, results,
      discussion, and conclusions), describes authorship guidelines that have been
      established by professional societies, and discusses the importance of adequate
      and correct references.

PMID- 15447808
TI  - How to write the methods section of a research paper.
AB  - The methods section of a research paper provides the information by which a
      study's validity is judged. Therefore, it requires a clear and precise
      description of how an experiment was done, and the rationale for why specific
      experimental procedures were chosen. The methods section should describe what was
      done to answer the research question, describe how it was done, justify the
      experimental design, and explain how the results were analyzed. Scientific
      writing is direct and orderly. Therefore, the methods section structure should:
      describe the materials used in the study, explain how the materials were prepared
      for the study, describe the research protocol, explain how measurements were made
      and what calculations were performed, and state which statistical tests were done
      to analyze the data. Once all elements of the methods section are written,
      subsequent drafts should focus on how to present those elements as clearly and
      logically as possibly. The description of preparations, measurements, and the
      protocol should be organized chronologically. For clarity, when a large amount of
      detail must be presented, information should be presented in sub-sections
      according to topic. Material in each section should be organized by topic from
      most to least important.

PMID- 15447809
TI  - Effective use of tables and figures in abstracts, presentations, and papers.
AB  - In some situations, tables, graphs, and figures can present certain types of
      information (including complicated relationships and sequences of events) more
      clearly and in less space than the same information would require in sentence
      form. However, do not use tables, graphs, and figures for small amounts of data
      that could be conveyed clearly and succinctly in a sentence. Also, do not
      reiterate in sentences the data that are shown in a table, graph, or figure: the
      point of creating a table or graph or figure is to eliminate that type of
      sentence from your manuscript. In building a data table you must balance the
      necessity that the table be complete with the equally important necessity that it
      not be too complex. Sometimes it is helpful to break a large table into several
      smaller ones to allow the reader to identify important information easily, but,
      conversely, it is a common mistake of novice authors to split up into several
      tables data that belong in one table. In almost all cases, only one table or
      graph or figure should be included in an abstract, and then only if it can convey
      essential information in less space and in a more easily interpretable way than
      the sentence form. For a poster, in almost all instances you should use only one
      typeface and one font in a table, graph, or figure. In general, do not use bold,
      italics, or color unless you are presenting a great deal of data and you need to
      highlight certain data values and you are certain that using bold, italics, or
      color will improve readability, which is rare. Do not include identical
      information in a table and a graph/figure. In reporting a clinical trial you will
      need to include a patient flow chart that identifies the number of patients
      initially screened for the study, the number of patients who were excluded (and
      why) after initial screening or in the final analysis, and how many patients
      entered, exited early, and completed each arm of the study. A treatment protocol
      should also be described with a flow chart. In preparing a graph the most common
      error is to include a line that suggests an unsubstantiated extrapolation between
      or beyond the data points. In selecting the graph's axes, avoid truncating,
      enlarging, or compressing the axes in ways that might make the graph confusing or
      misleading. To prepare clear, accurate, easily interpretable tables, graphs, and
      figures, rely on the rules described in authoritative guides such as the Council
      of Science Editors' Scientific Style and Format and the American Medical
      Association's Manual of Style.

PMID- 15447810
TI  - How to write an effective discussion.
AB  - Explaining the meaning of the results to the reader is the purpose of the
      discussion section of a research paper. There are elements of the discussion that
      should be included and other things that should be avoided. Always write the
      discussion for the reader; remember that the focus should be to help the reader
      understand the study and that the highlight should be on the study data.

PMID- 15447811
TI  - Searching the literature and selecting the right references.
AB  - The ability to locate published data on a topic is a fundamental skill in the
      research process, and it aids in formulating and refining a research question and
      planning the study. Searching the literature for published studies on a topic
      relevant to one's question requires knowledge of databases such as MEDLINE,
      Cumulative Index to Nursing and Allied Health, or Hospital Literature Index.
      PubMed provides access to MEDLINE and over 12 million citations in the medical
      literature. When searching in PubMed you can apply various "limits," such as what
      fields the search term is in (eg, author, title, text word, journal), type of
      report (eg, clinical trial, review, editorial), language, patient age, gender,
      and human or animal study. The "Boolean operators" (AND, OR, and NOT) can further
      focus and refine your search. However, to be sure that you retrieve all the files
      of interest and don't miss any files that might be critical to your understanding
      of the topic, you must search all fields and be careful not to exclude
      potentially important files with the NOT operator.

PMID- 15447812
TI  - The top 10 reasons why manuscripts are not accepted for publication.
AB  - This article discusses why many research projects that have been presented in
      abstract form are never published as full articles, and lists 10 reasons why
      manuscripts are not accepted for publication in Respiratory Care. Some of these
      reasons are easily avoidable or readily overcome. Included in this category is
      submission of manuscripts that do not correspond to the kinds of articles the
      Journal publishes, either in subject matter or in format. Poor writing impedes
      peer review and is unlikely to prejudice editors in an author's favor, although
      it is seldom the primary reason for rejection. Common deficiencies in the
      methods, results, and discussion sections prevent initial acceptance for
      publication but are at least potentially amenable to correction. More serious are
      fundamental defects in study design, which although correctable at the inception
      of a project, often doom the paper once the study has been completed. Two
      problems that are especially unfortunate for authors and potential readers alike
      are failing to revise and resubmit a manuscript after initial peer review and
      never preparing a full manuscript in the first place, after presentation of the
      work in abstract form. This special issue of Respiratory Care and other cited
      publications offer practical resources for authors to use in overcoming each of
      these problems.

PMID- 15447813
TI  - Association of the C(-1019)G 5-HT1A functional promoter polymorphism with
      antidepressant response.
AB  - Antidepressants, such as serotonin or noradrenaline reuptake inhibitors (e.g.
      fluoxetine, nefadozone) or 5-HT1A agonists (flibanserin), desensitize the 5-HT1A
      autoreceptor, which may contribute to their clinical efficacy. The 5-HT1A
      receptor gene is repressed by NUDR/DEAF-1 in raphe cells at the C-, but not at
      the G-allele of the C(-1019)G polymorphism that is associated with major
      depression and suicide. Depressed patients (n=118) were treated with
      antidepressants including fluoxetine or nefadozone combined with pindolol or
      flibanserin alone. The severity of depression was assesssed using the Hamilton
      Rating Scale for Depression. Although patients had similar severity initially,
      those with the homozygous G(-1019) genotype responded significantly less to
      flibanserin (p=0.039) and in pooled antidepressant treatment groups (p=0.0497)
      and were approximately twice as likely to be non-responders as those with the C(
      1019)C genotype. These results implicate the C(-1019)G 5-HT1A gene polymorphism
      as a potential marker for antidepressant response, suggesting a role for
      repression of the 5-HT1A gene.

PMID- 15447815
TI  - [Explore enteral nutrition and repair injured intestine].

PMID- 15447814
TI  - [The relationship between ecological immune nutrition and infection control under
      stress state].

PMID- 15447816
TI  - [Preliminary comparative study on the effects of early enteral supplementation of
      synbiotics on severely burned patients].
AB  - OBJECTIVE: To investigate the influence of early enteral nutrition with
      synbiotics on the plasma endotoxin level, the nutritional state, the inflammatory
      response and the incidence of infectious complications in severely burned
      patients. METHODS: Randomized double blind and control method was employed im the
      study. Forty severely burned patients were randomly divided into A and B groups
      with 20 in each group. The patients in group A received early enteral nutrition
      with synbiotics including four kinds of lactic acid bacteria and four kinds of
      fibers, while those in group B received early enteral nutrition with synbiotics
      including only four kinds of fibers. The patients with 80% to 280% coefficient
      unit burned surface(UBS) were further divided into A1 (n = 10) and B1 (n = 11)
      groups. The plasma endotoxin level in group A and B was determined dynamically on
      the 1st, 3rd, 7th, 10th, 14th, and 21st postburn days (PBD), and its abnormal
      rate in both groups was statistically analyzed in correlation with the normal
      endotoxin level. meanwhile, the mortality, the incidence of infectious
      complications and the blood bacterial culture results were compared between the
      two groups. The plasma levels of IL-1, IL-6 and prognostic inflammatory nutrition
      index (PINI) were also determined at the above time points. RESULTS: The plasma
      endotoxin level in group A (37.9 +/- 5.4) ng/L was evidently lower than that in
      group B (59.1 +/- 7.9) ng/L (P < 0.05) on 10 PBD. The abnormal rate of plasma
      endotoxin in group A (36.7%) was evidently lower than that (49.2%) in group B (P
      < 0.05). Blood culture was positive in 3 patients in group A, and 5 in group B.
      There was no obvious difference in the incidence of infectious complication
      between the two groups. Two patients died in group A and 1 group B. There was no
      obvious difference in plasma IL-1 level between A1 and B1 groups at different
      time points. The plasma IL-6 level in A1 group in 10th and 14th PBD was evidently
      lower than that in B1 group (P < 0.05). The PINI in A1 group on the 10 PBD was
      remarkably lower than that in B1 group. CONCLUSION: Early enteral nutrition with
      synbiotics was helpful in decreasing inflammatory stress response and lowering
      the plasma endotoxin level. Enteral supplementation of synbiotics might be
      beneficial to the controlling of burn infection.

PMID- 15447817
TI  - [The protective effect of supplementation of probiotics combined with riboflavin
      on the intestinal barrier of the rats after scald injury].
AB  - OBJECTIVE: To investigate the effect and its possible mechanism of the
      supplementation of probiotics combined with riboflavin on the intestinal barriers
      of the rats after scald injury. METHODS: Seventy Wistar rats were used in the
      study and were randomly divided into scald control (SC, n = 30), scald and
      treatment (ST, n = 30) and normal control (NC, n = 10) groups. The rats in SC and
      ST groups were subjected to 30% TBSA III degree scald. 1.5 ml of isotonic saline
      suspension containing 5 x 10(12) CFU/L of Bifidobacteria, 5 x 10(10) CFU/L of
      Bacillus cereus and 5 mg/L of riboflavin was given to rats by gavage in ST group
      twice a day. For the rats in SC and NC group equal amount of isotonic saline was
      fed twice a day. The changes in the incidence of bacterial translocation, the
      amount of intestinal membranous flora, the synthesis and secretion of SIgA in the
      ileum, and the repair of injured intestinal mucosa were observed. RESULTS: The
      incidence of bacterial translocation in ST group was significantly lower than
      that in SC group (P = 0.000 - 0.025). The plasma level of endotoxin in ST group
      was markedly lower than that in SC group on 3 post-scald day (PSD) (P < 0.05).
      The amount of bifidobacteria in caecal membrane flora increased by about 20 to 40
      fold, whereas the amounts of E. coli and fungi significantly decreased (P <
      0.01). The membranous injury scoring was 3 to 0 on 5 PSD (P < 0.05), and the SIgA
      content in intestinal mucus returned to normal value on the 5th PSD (P < 0.01) in
      the ST group. CONCLUSION: Supplementation of probiotics together with riboflavin
      could ameliorate translocation of bacteria and endotoxin in rats with scald
      injury, implying that the intestinal barrier function was effectively protected.

PMID- 15447818
TI  - [Analysis of the therapeutic effect and the safety of glutamine granules per os
      in patients with severe burns and trauma].
AB  - OBJECTIVE: To observe the therapeutic effect and possible side effects of
      glutamine granules per os in patients with trauma, burns and major operations.
      METHODS: Patients inflicted with severe burns, trauma and major operations were
      enrolled in the study. One hundred and twenty patients were randomly divided into
      two groups, 60 in control group (C) and 60 in glutamine group (Gln). Randomized
      double blind and placebo control methods were employed in the study. All the
      patients in both groups were given diet with equal calories and equal nitrogen
      content. The patients in Gln group received glutamine granules in dose of 0.5
      g.kg(-1).d(-1) orally or by gavage, while those in C group received same dose of
      placebo (glycine) for 7 days. The changes in the intestinal mucosal barrier
      function, the protein metabolism, the immune function, hepatic and renal
      functions, and the incidence of side effects of the medication in both groups of
      patients were observed and compared before and after the supplementation of
      glutamine or glycine. RESULTS: The plasma contents of glutamine, proteins and
      interleukin 2 in both groups were all lower than normal values. But the plasma
      diamine oxidase (DAO) activity, endotoxin content, intestinal mucosal
      permeability (urine lactose/mannitol, L/M) and urine excretion of nitrogen
      increased obviously in both groups. The plasma glutamine concentration in Gln
      group increased by 38.04% after the administration of Gln for 7 days (P < 0.01).
      The plasma contents of pro-albumin, transferrin, and IL-2 were obviously higher
      than those in the C group (the increase rates were 21.19%, 51.11%, 57.54%,
      respectively, P < 0.01). The plasma DAO activity, L/M ratio, endotoxin content
      and urine nitrogen excretion in Gln group were evidently lower than those in C
      group (the decrease rates were 47.26%, 52.18, 22.22% and 27.78%, respectively, P
      < 0.05 or 0.01). There was no obvious difference in the plasma levels of total
      protein and albumin, the indices in blood and urine test, or the hepatic and
      renal functions between the two groups before and after the amino acid
      supplementation. Mild side effects such as nausea, diarrhea, constipation
      occurred in both groups, but all of them disappeared spontaneously afterwards (P
      > 0.05). CONCLUSION: Oral administration of glutamine could be helpful to
      increase plasma concentration of glutamine and to ameliorate obviously the
      intestinal mucosal injury, to promote systemic protein synthesis and to inhibit
      protein catabolism and to upgrade systemic immune function with little side
      effect in patients with severe injury.

PMID- 15447819
TI  - [The influence of L-arginine on the angiogenesis in burn wounds in diabetic
      rats].
AB  - OBJECTIVE: To investigate the possible mechanism of L-arginine supplementation on
      the angiogenesis of burn wounds in diabetic rats. METHODS: One hundred male
      Sprague-Dawley (SD) rats were used in the study and were randomly divided into A
      (scalding control, n = 25), B (scalding of the rats with diabetes, n = 25), C (L
      glycine control, n = 25) and D (L-arginine supplementation, n = 25) groups.
      Diabetes was produced by intra-peritoneal injection of streptozotocin (STZ) in B,
      C and D groups. The rats in C and D groups were gavaged with L-glycine and L
      arginine in dose of 200 mg.kg(-1).d(-1), respectively. The glucose content of the
      back skin tissue was determined for five rats in each group eight weeks after STZ
      administration. Deep partial thickness scalding of 20% TBSA was engendered on the
      back in the other 80 rats. The wound area, wound healing rate, and microvascular
      density with CD34 immunohistochemistry staining were determined on 3rd, 7th,
      14th, and 21st post scalding days (PSDs), In addition, the amount of nitric oxide
      (NO) released from the wound tissue and the tissue contents of vascular
      endothelial growth factor (VEGF) and transforming growth factor beta1 (TGF-beta1)
      from wound were determined at the above time points. RESULTS: Compared to those
      in group B, the wound healing rate in group D increased significantly since the
      7th PSD [(44.10 +/- 3.50)%, P < 0.05], and the wound MVD value was increased
      significantly at all postburn time points. Furthermore, the levels of VEGF, NO
      and TGF-beta1 in the wound tissue was also increased significantly, while the
      glucose content in the cutaneous tissue was decreased to (1.380 +/- 0.120) mg/g.
      CONCLUSION: L-arginine supplementation could be beneficial to the angiogenesis in
      the burn wound of the rats with diabetes, as well as to wound healing by
      increasing the synthesis and the release of VEGF, NO and TGF-beta1 from burn
      wound and by decreasing the glucose content in the cutaneous tissue of diabetic
      rats.

PMID- 15447820
TI  - [An experimental study on the relationship between the extracellular matrix and
      apoptosis of intestinal epithelium after burn injury].
AB  - OBJECTIVE: To explore the relationship between the extracellular matrix and
      apoptosis of intestinal epithelium after burn injury. METHODS: Thirty Wistar rats
      were employed in the study and were randomly divided into normal control (C) and
      6 PBH (postburn hour), 12 PBH, 1 PBD (postburn day), 3 PBD and 5 PBD group with 5
      rats in each group. The rats in burn groups were sacrificed at 0, 6 and 12 PBHs
      and 1, 3 and 5 PBDs. The apoptotic cell count and the caspases-3 activity of
      intestinal mucosal epithelium, and the extracellular matrix component laminin and
      type IV collagen were determined and their correlation was analyzed. RESULTS: The
      apoptotic cell count and the caspases-3 activity of intestinal mucosal epithelium
      in burn groups were obviously higher than those in C group (P < 0.05 or 0.01),
      while the intestinal mucosal contents of laminin and type IV collagen in burned
      groups were much lower than those in C group (P < 0.05 or 0.01). By linear
      correlative analysis, it was shown that the changes in the intestinal mucosal
      contents of laminin and type IV collagen in burned groups were negatively
      correlated with the change in apoptotic cell count (r = -0.575, -0.613, P <
      0.05). CONCLUSION: Intestinal epithelial apoptosis was enhanced after burn
      injury, and it was correlated with the change in the components of the
      extracellular matrix.

PMID- 15447821
TI  - [Comparative study on the enteral and parenteral nutrition during early postburn
      stage in burn patients].
AB  - OBJECTIVE: To investigate the influence of early enteral nutrition on the
      nutritional indices of the burn patients. METHODS: Thirty-seven burn patients
      were enrolled in the study and were randomly divided into early enteral nutrition
      (EN) and parenteral nutrition (PN) groups. The body weight, serum levels of
      prealbumin and transferrin, the incidence of burn sepsis, and the hospital stay
      days were surveyed respectively and compared between these two groups. RESULTS:
      The percentage of body weight loss in EN group was obviously lower than that in
      PN group on the 7th and 14th post burn day (PBD) (P < 0.05). The serum contents
      of prealbumin and transferrin in EN group were significantly higher than that in
      PN group on the 4th, 8th and 14th PBD (P < 0.05 or 0.01). The incidence of burn
      sepsis in EN group was lower than that in PN group (5.56% vs 31.58%, P < 0.05).
      The hospital stay days in EN group were less than that in PN group (40.39 +/-
      10.81 d vs 54.89 +/- 11.26 d, P < 0.01). CONCLUSION: Early enteral nutrition is
      beneficial to the improving of nutrition state of the burn patients, and to the
      reduction of the incidence of burn sepsis and the hospitalization time.

PMID- 15447822
TI  - [The influence of combined supplementation of glutamine and recombinant human
      growth hormone on the protein metabolism in severely burned patients].
AB  - OBJECTIVE: To investigate the influence of combined supplementation of glutamine
      (Gln) and recombinant human growth hormone (rhGH) on the protein metabolism in
      severely burned patients. METHODS: Sixty severely burned patients were enrolled
      in the study and were randomly divided into control (C, n = 20) and Gln with rhGH
      (Gln + rhGH, n = 20) groups. The patients in C group received glycine as the
      placebo, while those in Gln group took Gln orally in dose of 0.5 g kg(-1) d(-1)
      during 1-14 postburn days (PBDs). For the patients in Gln + rhGH group rhGH was
      administered subcutaneously in dose of 0.2 U kg(-1) d(-1) in addition to
      glutamine in same dosage beginning on the 7 PBD for 7 days. The plasma Gln
      concentration in the 3 groups of patients was determined on the 1st, 7th and 14th
      PBD and the plasma albumin level was determined on 14th and 21st PBD. The wound
      healing rate of the patients within 30 PBSs and the total hospital stay days were
      recorded. RESULTS: The plasma Gln concentration in Gln + rhGH group of patients
      was evidently higher than that in C group after 7 PBD[(452.28 +/- 21.72)
      micromol/L vs(325.12 +/- 25.34) micromol/L, P < 0.05]. The plasma albumin level
      in Gln + rhGH group was obviously higher than that in C and Gln groups on the
      21st PBD (P < 0.05). The wound healing rate in Gln + rhGH group was evidently
      higher than that in Gln and C groups on the 30th PBD (P < 0.05). The total
      hospital stay days in Gln + rhGH group were obviously less than that in C and Gln
      groups (P < 0.05 or 0.01). CONCLUSION: Combined administration of Gln and rhGH
      could be beneficial to the elevation of plasma Gln level in severely burned
      patients and the systemic protein synthesis was therefore enhanced and the wound
      healing rate was improved.

PMID- 15447823
TI  - [Repair of the penial injury in patients inflicted by high-voltage electrical
      injury].
AB  - OBJECTIVE: To explore the repair and reconstruction of penial defect in patients
      inflicted by high-voltage electrical injury. METHODS: Among one hundred and fifty
      three patients inflicted with high-voltage electrical injury, 6 suffered from
      penial injury (including 3 with necrosis of whole penis, 1 with partial necrosis
      of penis, 1 with partial necrosis of penial shin and 1 with necrosis of entire
      skin of penis) were enrolled in the study. The penis was repaired by direct
      suture of the residual skin following excision of necrotic skin in one case, by
      skin grafting in two case, by scrotum skin flap transplantation in 3 cases.
      RESULTS: The appearance and function of the penis in three cases were
      satisfactory, and the result was also satisfactory in one patient who underwent
      reconstructive operation at late post injury stage. The penis was totally lost in
      2 patients. CONCLUSION: The skin necrosis of penis after high-voltage injury
      could be repaired with scrotum skin flap. Total necrosis of the penis could be
      reconstructed with abdominal skin flap.

PMID- 15447824
TI  - [One-stage reconstruction of postburn whole auricle defect with MEDPOR ear
      scaffold covered with superficial temporoparietal fascia flap].
AB  - OBJECTIVE: To study the effect and the key points in the operative procedure of
      the one-stage reconstruction of postburn whole auricle defect with medpor car
      scaffold covered with superficial temporoparietal fascia (TPF) flap. METHODS:
      Medpor car scaffold was embedded under the superficial temporal (TFP) fascia.
      Razor-thin skin was grafted onto the surface of the fascia flap. RESULTS: Fifteen
      patients with postburn whole auricle defect were treated by one-stage
      reconstruction with Medpor ear scaffold during the last four years. It was
      successful in all the patients with satisfactory appearance of the reconstructed
      ears. CONCLUSION: Medpor possessed friendly biological compatibility. The
      reconstruction gave satisfactory results, and its advantages consisted of short
      operational time, easy manipulation, less injury to patients and good auricular
      contour.

PMID- 15447825
TI  - [Influence of mixed grafting of autologous and allogeneic microskin on burn wound
      healing in rats].
AB  - OBJECTIVE: To observe the influence of mixed grafting of autologous and
      allogeneic microskin on burn wound healing. METHODS: Autologous microskin
      grafting (expansion rate 5:1) was employed as control. Autologous microskin mixed
      with the allogeneic microskin with the thickness of 0.3 mm and 0.6 mm,
      respectively, were designated as experimental groups 1 and 2 (EP1 and EP2). The
      wound healing rate, wound contraction rate, and histological changes were
      observed on the 2nd, 3rd and 4th weeks after the grafting. RESULTS: The wound
      healing rate in two experimental groups (94.58 +/- 3.99)% in EP1, and (95.28 +/-
      1.93)% in EP2 was significantly higher than that in the control group (88.28 +/-
      6.85)% at the end of the 2nd week after the grafting (P < 0.05) The wound healing
      rate in experimental group 2 (94.55 +/- 3.47)% was obviously higher than that in
      control (88.51 +/- 5.59)% and experimental group 1 (89.51 +/- 4.70)% at the end
      of the 3rd week after grafting (P < 0.05). There was no obvious difference in
      wound healing rate among the three groups at the end of the 4th week after
      grafting. Obvious lymphocytic infiltration was observed by histological
      examination between epidermis and dermis in the two experimental groups at the
      end of the 2nd week after grafting. But there was no obvious difference among the
      three groups 4 weeks after grafting. CONCLUSION: The wound healing could be
      improved by mixed skin grafting with appropriate quantity of allogeneic and
      autologous microskin. Furthermore, the wound contraction could be ameliorated if
      the thickness of allogeneic dermis was increased in the mixed grafting even with
      the same proportion of allogeneic to autologous microskin.

PMID- 15447826
TI  - [Comparative study of binding power of polymyxin B and its simulating peptide to
      lipopolysaccharides lipoid A].
AB  - OBJECTIVE: To observe the binding power of polymyxin B (PMB) and its simulation
      peptide to lipopolysaccharide (LPS) and lipoid A. METHODS: LPS and lipoid A were
      separately coated on biosensor. 5 microl of PMB (0.01 microg/L) 5 microl of its
      simulating peptide 1 (PMBSP1 0.01 microg/L) and 5 microl of its simulating
      peptide 2 (PMBSP2, 0.01 microg/L) were respectively added into the hydrophobic
      sample pool. The combining power of PMB and its simulating peptides PMBSP1 and
      PMBSP2 to LPS and lipoid A was compared. RESULTS (1) PMBSP1 almost did not bind
      LPS and lipoid A, while PMB and PMBSP2 possessed high affinity with LPS and
      lipoid A. (2) The peak value (98.41 +/- 7.31) rad/s of PMBSP2 binding LPS was
      much higher than that (83.58 +/- 5.42) rad/s of PMB in binding LPS (P < 0.05).
      While the peak value of PMB in binding lipoid A was similar to that of PMBSP2.
      (3) The peak value of PMB binding LPS was significantly lower than that of PMB in
      binding lipoid A (P < 0.05). But there was no difference between the peak value
      of PMBSP2 in binding LPS and that of PMBSP2 in binding lipoid A. (4) PMBSP2 could
      bind to LPS and lipoid A in a shorter time to reach peak levels. CONCLUSION:
      Compared with PMB, the PMBSP2 could bind to LPS and lipoid A in a shorter time.
      In addition, PMBSP2 exhibited similar affinity to LPS and lipoid A. This
      indicated that PMBSP might possess better anti-LPS activity due to its lack of
      space steric hindrance when PMBSP binding the lipoid A of LPS.

PMID- 15447827
TI  - [Mechanism of the role of electrical field in electrical injury].
AB  - OBJECTIVE: To explore the acting mechanism of electrical field in electrical
      injury. METHODS: Thirty-six New Zealand white rabbits were employed in the study
      and were randomly divided into 7 groups. There were 12 rabbits in group 1 and 4
      in each group of other 6 groups. The animal model of nonthermal electrical injury
      previously replicated was employed in the study. Experiment with paralleled
      muscular fibers in electrical field was carried out in groups 2 approximately 4,
      while that of vertical muscular fibers in electrical field in groups 5-7.
      Anatomical examination was done to determine the index of deep burn injury (IDBI)
      in all groups of rabbits at 0, 2 and 24 postburn hour (PBH). Histological and
      ultrastructural examination, gamma picturing and isotope scanning with 99mTc were
      done in group 1 at 2 PBH. RESULTS: There was no obvious skin injury in the white
      rabbits in group 1. Deep tissue necrosis was identified under the small
      electrode. Constant muscular spasm was observed in the inner side of the thigh.
      The muscles in paralleled electrical field suffered more severe injury than those
      in vertical one. Tissue injury was more severe in those areas with higher current
      density, less soft tissue, and also in the central area of the axis of the
      electric field. There were obvious changes in the perfusion and blood pool phases
      in these areas as observed with the aid of 99mTc. Light microscopic examination
      revealed swelling and necrosis of muscular fibers. Under electron microscopy, it
      was found that there were edema and dissolution with separation of lipid
      molecular layers of cell membrane, Shortened nucleus with partial dissolution of
      nuclear membrane, increased heparin granules within nucleus, swelling of
      mitochondria and endoplasmic reticulum, myofilament dissolution, expanded gap
      between myofilament and decreased number of heparin granules. CONCLUSION: Non
      thermal tissue injury in the electrical field, in terms of cell, ultrastructural
      and molecular levels, was induced and aggravated by all the factors constituting
      high voltage electrical field.

PMID- 15447838
TI  - [In vivo tissue engineering: a new concept].
AB  - From our over a decade-long experience in experiments and clinical applications
      of human hair keratin (HHK) artificial tendon, a conclusion was drawn that HHK
      artificial tendon components and their degradation products could stimulate the
      proliferation and differentiation of tenoblasts in the neighboring tissues into
      tenocytes. With the regulation of this process by certain cytokines secreted by
      other cells, autotendons can be finally formed. We also found that after grafting
      for the tissue defects such as in the bone, nerve and muscle, "in situ
      construction" of the tissue/organ substitutes occurred, which inspired us to
      propose a wholly new theoretical system--in vivo tissue engineering, defined as
      in vivo reconstruction of the defected tissues or organs. The grafted absorbable
      scaffold biomaterial itself and its degradation products can activate the
      mitosis, proliferation, and differentiation of adult stem cells in the
      surrounding tissues, which organically interact with the material to form an
      organic complex under in vivo physiological conditions. Finally the matrix
      material is completely replaced by the complex, an almost identical structure
      with the normal tissue in terms of anatomy and histology. One of the advantages
      of in vivo tissue engineering is "in vivo construction" of the tissue/organ
      substitutes in anatomy, histology and function way of "in vivo cultivation" of
      the seed cells under in vivo microenvironment and in vivo precise regulation
      mechanism. It solves such problems as immune rejection against seed cells,
      variation and functional deterioration of the seed cells, complicated
      preservation procedure, transportation and high cost. The most prominent
      advantage of this technique is that it best meets the clinical need, not only in
      the sense of its powerful clinical potential, but also in its significant
      theoretical value.

PMID- 15447839
TI  - [Green tea polyphenols inhibit low-density lipoprotein-induced proliferation of
      rat vascular smooth muscle cells].
AB  - The proliferation and migration of vascular smooth muscle cells (VSMCs) is one of
      the major mechanisms of intimal thickening in atherosclerosis and post
      angioplasty restenosis. Elevated plasma levels of low-density lipoprotein (LDL)
      have been implicated in the pathogenesis of atherosclerotic vascular diseases.
      The purpose of this study was to determine the effects of green tea polyphenols
      on the proliferation and p44/42 mitogen-activated protein kinase (MAPK) activity
      in rat VSMCs simulated by native LDL. Rat aortic VSMCs were cultured and treated
      with LDL (100 microg/ml) in the absence or presence of green tea polyphenols, and
      the cell proliferation was subsequently quantified by non-radioactive MTS/PES
      assay and the cell cycle analyzed by flow cytometry. The p44/42 MAPK activity was
      evaluated by immunoblotting using anti-p44/42 phospho-MAPK antibody. Compared
      with the cells without polyphenol treatment, the proliferation of the VSMCs
      induced by LDL was dose-dependently inhibited by green tea polyphenols (P<0.05),
      with more numerous cells in G(0)G(1) phase (P<0.05) as shown by flow cytometry
      analysis. LDL significantly enhanced the p44/42 MAPK activity, an effect
      obviously inhibited by green tea polyphenols (at 100 microg/ml). These results
      suggest that green tea polyphenols can inhibit high levels of LDL-induced
      proliferation of phosphorylated p44/42 MAPK expression in rat VSMCs. Green tea
      polyphenols may, therefore, offer vascular protection by inhibiting VSMC growth
      in response to hypercholesterolemia.

PMID- 15447840
TI  - [Expression of ABCA1 in vascular endothelial cells and its significance in the
      pathogenesis of atherosclerosis].
AB  - OBJECTIVE: To investigate the changes in the expressions of ATP-binding cassette
      transporter A1 (ABCA1), intercellular cell adhesion molecule type 1 (ICAM-1) and
      monocyte chemoattractant protein-1 (MCP-1) at mRNA and protein levels after the
      treatment of the vascular endothelial ECV304 cells with oxidized low-density
      lipoprotein (Ox-LDL) and 8-Br-cAMP, thereby to explore possible mechanisms by
      which ABCA1 affects the formation of atherosclerosis (AS). METHODS: Resuscitated
      and cultured ECV304 cells were incubated in serum-free medium for 12 h to induce
      the quiescence phase of growth, which were subsequently treated with Ox-LDL (30
      ng/ml) and 8-Br-cAMP (0.5 mmol/L) respectively for 3, 6, 12, and 24 h. After the
      cells were harvested at the specified time points, the mRNA and protein levels of
      ABCA1, ICAM-1 and MCP-1 were detected by RT-PCR and Western blotting,
      respectively. RESULTS: The mRNA and protein expression levels of ABCA1, ICAM-1
      and MCP-1 all increased after treatments with Ox-LDL and 8-Br-cAMP. The highest
      expression of ICAM-1 occurred in cells with a 12-hour treatment, and those of
      ABCA1 and MCP-1 occurred following 6-hour incubation with Ox-LDL. The expression
      peaks of ABCA1, ICAM-1 and MCP-1 all took place after 6-hour incubation with 8-Br
      cAMP. CONCLUSIONS: The mRNA and protein expressions of ICAM-1 and MCP-1 in
      vascular endothelial ECV304 cells increase in response to Ox-LDL treatment, in
      the event of which ABCA1 is also up-regulated to offer protective effects against
      AS. cAMP not only enhances the expression of ABCA1 but also those of ICAM-1 and
      MCP-1.

PMID- 15447841
TI  - [Primary culture of histaminergic neurons in neonatal rat hypothalamus
      tuberomammillary nucleus].
AB  - OBJECTIVE: To establish primary cell culture conditions for tuberomammillary
      nucleus (TM) histaminergic neurons of neonatal rats. METHODS: The
      tuberomammillary nucleus was dissected from the posterior part of the
      hypothalamus of neonatal rats, and neurobasal medium supplemented with B27 was
      used for the primary cell culture. The cultured neurons were identified by
      immunocytochemical method (ICC). RESULTS: TM neurons from the hypothalamus of
      neonatal rats were successfully cultured under the experimental condition and
      tended to mature morphologically on the days 7 to 9 of culture. The cultured
      neurons were stained by ICC and the green immunoreaction product was seen in the
      neurons under the fluorescence microscope, indicating that the cultured neurons
      were histamine-positive. CONCLUSION: TM neurons in the hypothalamus of neonatal
      rats can be cultured in vitro, and the primary cultured ones may serve as a cell
      model in vitro for the researches of central histaminergic system.

PMID- 15447842
TI  - [Phospholipase C-gamma1 dynamic mRNA expression patterns in rats during early
      postnatal period].
AB  - OBJECTIVE: To investigate the expression of phospholipase C-gamma1 (PLCG1) mRNA
      in rats during early postnatal period. METHODS: Semi-quantitative reverse
      transcription-polymerase chain reaction (RT-PCR) was used to detect the
      expression of PLCG1 mRNA in 28 samples extracted from the liver, lung, kidney and
      brain of rats aged 1, 3, 5, 7 days, and 2, 3, 5 weeks. Specific PLCG1 product and
      GAPDH product as the internal control were both amplified by RT-PCR, and the
      ratio of their integral optical density was calculated to estimate the relative
      mRNA expression of PLCG1. RESULTS: PLCG1 was expressed in rat liver, lung, kidney
      and brain at the 7 postnatal time points, and the expression varied significantly
      with time and between the different organs (P<0.01), virtually undetectable in
      the liver on postnatal day 1 and reaching the highest level in the brain tissues
      on postnatal day 7. CONCLUSION: The differences in PLCG1 expression in various
      organs and development periods suggest that PLCG1 is involved in cell
      proliferation and differentiation during the early development of rats.

PMID- 15447843
TI  - [Role of intron and 5' untranslated region in human thrombopoietin gene
      expression].
AB  - OBJECTIVE: To study the role of 5' untranslated region (UTR) and intron in the
      expression of human thrombopoietin (TPO) gene. METHODS: A number of expression
      vectors containing TPO mini-gene fused to the regulatory elements of
      cytomegalovirus (CMV) were constructed and transfected via lipofectin into
      cultured cos-1 cells for transient expression of TPO gene. The cell culture media
      were analyzed with highly sensitive sandwich enzyme-linked immunosorbent assay
      (ELISA) 48 h after the transfection. RESULTS: The expression levels of the TPO
      gene elements followed the order of TPO intron v> TPOcDNA> TPO intron I> TPO
      intron I> TPO gDNA in cos-1 cells. CONCLUSION: The last intron of TPO gene
      obviously enhances the expression level of TPO gene, which can be inhibited by
      5'UTR of TPO gene.

PMID- 15447844
TI  - [Renaturation of thermolabile hemolysin inclusion bodies expressed by Vibrio
      parahaemolyticus].
AB  - OBJECTIVE: To clone and construct expression vector pET32a+-tlh to acquire
      biologically functional thermolabile hemolysin of Vibrio parahaemolyticus.
      METHODS: tlh gene was cloned and the expression vector pET32a+-tlh constructed.
      The tlh gene of Vibrio parahaemolyticus was expressed in DE3 in the form of
      inclusion body, which was resolved in 8 mol/L urea followed by purification of
      the fusion protein using affinity chromatography and renaturation through
      gradient dialysis, protein concentration reduction and oxidoreduction. RESULTS
      AND CONCLUSION: The purified and renatured protein possessed hemolytic and
      immunogenic activities.

PMID- 15447845
TI  - [Effect of astrocyte-conditioned medium on tert-butyl hydroperoxide-induced
      apoptosis of PC12 cells].
AB  - OBJECTIVE: To investigate the effect of astrocyte-conditioned medium (ACM) on
      PC12 cell apoptosis induced by reactive oxygen species tert-butyl hydroperoxide
      (tbOOH). METHODS: PC12 cells attacked by tbOOH were cultured with Sprague Dawley
      rat cerebral cortex ACM, and the cell apoptosis was observed by fluorescent
      microscopy and transmission electron microscopy. The cell apoptosis rate was
      evaluated by flow cytometry and malondialdehyde (MDA) concentration measured
      using thiobarbituric acid (TBA)-reacting substances (TRABS). RESULT: TbOOH
      induced PC12 cell apoptosis, and ACM significantly decreased the apoptosis rate
      and MDA concentration in tbOOH-treated cells. CONCLUSION: ACM may increase the
      anti-oxidation capacity of PC12 cells and inhibit cell apoptosis induced by
      tbOOH.

PMID- 15447846
TI  - [Difference in gene expression profile of human polymeric immunoglobulin receptor
      transfected mouse nasopharyngeal epithelial cells before and after EBV
      infection].
AB  - OBJECTIVE: To study the gene expression profile of human polymeric immunoglobulin
      receptor gene (hpIgR)-transfected mouse nasopharyngeal epithelial cells
      transformed with n, n'-dinitrosoperazine (TMNE) before and after EBV infection
      using cDNA array and investigate the role of Epstein-Barr virus (EBV) infection
      in the tumorigenesis of nasopharyngeal carcinoma (NPC). METHODS: The total RNAs
      of hpIgR-transfected TMNE cells before and after EBV infection were extracted,
      reversely transcribed, and labeled with alpha -(32)P-dATP. The cDNA probes were
      hybridized to the Atlas mouse cancer array 1.2, and the signals analyzed by
      AtlasImage software. RESULTS: Twenty-five genes differentially expressed in cells
      before and after EBV infection, including 23 up-regulated genes and 2 down
      regulated genes. CONCLUSIONS: The gene expression profile of hpIgR-transfected
      TMNE cells may change after EBV infection, suggesting that these genes are
      probably involved in the tumorigenesis and progression of NPC.

PMID- 15447847
TI  - [Extraction and separation of koumine from Gelsemium alkaloids].
AB  - OBJECTIVE: To establish a method for isolating and identifying koumine. METHODS:
      Koumine was first extracted from Gelsemium alkaloids by using chloroform, which
      was further separated and purified by column chromatograph, and identified by
      thin-layer chromatography. RESULTS AND CONCLUSION: Koumine crystals were isolated
      and purified from Gelsemium alkaloids effectively.

PMID- 15447848
TI  - [Synergistic effects of paclitaxel and gemcitabine on androgen-independent
      prostate cancer].
AB  - OBJECTIVE: To observe the synergistic effects of paclitaxel (PA) and gemcitabine
      (GE) in vitro and in vivo on prostate cancer cell line PC-3. METHODS: Cell
      morphological observation, MTT assay, flow cytometry, and immunocytochemical
      method were used to observe the effects of 1+/-10(-6) mol/L, 1 x 10(-7) mol/L and
      1 x 10(-8) mol/L PA and 1 x 10(-7) mol/L, 1 x 10(-8) mol/L and 1 x 10(-9) mol/L
      GE on prostate cancer cell line PC-3 in vitro in a single or combined
      administration for 48 h. Male BALB/C-nu mice bearing PC-3 prostate cancer were
      treated with docetaxol and retinoic acid singly or synergistically, followed by
      measurement of the body weight and immunohistochemical examination of serum
      prostate specific antigen (PSA) and PSA expression in the implanted tumors.
      RESULTS: GE at the concentration of 1 x 10(-8) mol/L significantly enhanced the
      effect of PA above 1 x 10(-7) mol/L in inducing growth inhibition (with an
      inhibition rate over 50.8%+/-4.2%, P<0.05) and apoptosis (apoptosis rate over
      22.9%+/-2.3%, P<0.05) of PC-3 cells and in down-regulating the expression of
      cyclin D1 (expression rate no higher than 9.6%+/-1.6%, P<0.01) in PC-3 cells. GE
      lowered the rate of PA-induced cell cycle arrest at G(2)/M phase from 70.3%+/
      9.7% to 38.2%+/-4.2%, and partially reversed the G(2)/M arrest (P<0.01).
      Synergistic treatment of the tumor-bearing mice caused little change in the body
      weight, but the serum PSA (51+/-14 ng/ml), implanted tumor mass (3.2+/-0.5 g) and
      PSA expression in the tumors (30%+/-3.7%) were all decreased significantly in
      comparison with the control mice (21.6+/-1.7 g). CONCLUSIONS: GE can enhance PA
      induced tumor cell growth suppression and apoptosis in a synergistic manner both
      in vitro and in vivo, suggesting their great potential in clinical treatment of
      androgen-independent prostate cancer.

PMID- 15447849
TI  - [Aspirin inhibits proliferation and expression of p44/42 MAPK phosphorylation in
      vascular endothelial cells].
AB  - OBJECTIVE: To observe the effects of aspirin on vascular endothelial cell
      proliferation in vitro and on the activity of p44/p42 mitogen-activated protein
      kinase (MAPK) phosphorylation. METHODS: ECV 304 cells cultured in vitro were
      treated with aspirin (1, 2, 5, and 10 mmol/L, respectively) and observed for
      their proliferation in comparison with the control group. The ratio of cell
      proliferation was determined by non-radioactive MTS/PES assay. The expression of
      phosphorylated p44/42 MAPK protein was evaluated by the immunoblotting technique
      using anti-p44/42 phospho-MAPK antibody. RESULTS: The proliferation rate of the
      endothelial cell was 1.533+/-0.286 in the control group, and 0.459+/-0.107,
      0.708+/-0.125, 0.953+/-0.149 and 1.253+/-0.225 in aspirin-treated groups
      corresponding to aspirin concentrations of 10, 5, 2 and 1 mmol/L, respectively.
      It was shown that aspirin significantly inhibited the vascular endothelial cell
      proliferation at the concentration above 1 mmol/L (P<0.05), in a dose-dependent
      manner as compared with the control group (P<0.05). The expression of
      phosphorylated p44/42 MAPK protein was significantly inhibited by aspirin.
      CONCLUSIONS: Aspirin decreases vascular endothelial cell proliferation, and
      arrest of endothelial cell proliferation may be an important mechanism by which
      aspirin produces protective effect against acute coronary disease.

PMID- 15447850
TI  - [Identification of two new strains of norovirus in Guangzhou].
AB  - OBJECTIVE: To identify the molecular biological characteristics of human
      caliciviruses (HuCVs) and new strains of norovirus (NV) detected in Guangdong
      Province. METHODS: HuCVs were detected from the stool specimens by reverse
      transcription-PCR (RT-PCR), and the PCR products were cloned, transformed, and
      blasted with Genbank. The nucleotide sequence homology was also evaluated with
      PHYLIP package, and the phylogenetic tree was generated by Treeview. RESULTS:
      HuCVs were detected from 18 out of 206 stool specimens from children with viral
      diarrhea (8.74%), which were all confirmed subsequently as NVs. Two strains
      HuCV/NVGII 003/2003/CHN(32282) and HuCV/NVGII 004/2003/CHN(32283) from the
      selected 6 NVs strain were identified as new NV strains. CONCLUSION: New NV
      strains in consistency with the blood-type distribution of Chinese are present in
      Guangzhou, which have not been reported in other countries.

PMID- 15447851
TI  - [Impact of early-stage hepatic ischemia-reperfusion injury on other organs of
      rats].
AB  - OBJECTIVE: To investigate the influence of hepatic ischemia-reperfusion on other
      organs of rats during the early stage of injury. METHODS: Twenty-five healthy
      male SD rats were randomized equally into 5 groups according to the different
      time points in the course of hepatic vascular occlusion and reperfusion, namely
      pre-occlusion, the end of occlusion, and after 0.5, 2.0 and 6.0 h reperfusion,
      respectively. In each group the rats were killed to obtain samples at the
      specified time points. The contents of malondialdehyde (MDA) and superoxide
      dismutase (SOD) in the lung, kidney, pancreas and heart were measured in pre
      occlusion and 6-hour reperfusion groups. The triphosphate (ATPase) activity in
      heart tissues, the contents of MDA and the activity of SOD in blood and the blood
      biochemistry were observed in different groups. RESULTS: The activity of SOD and
      ATPase were decreased (P<0.05) after the ischemia-reperfusion as compared with
      those before ischemia, but the contents of MDA, ALT, AST BUN, AMY and CK-MB
      increased significantly (P<0.05). CONCLUSION: Liver ischemia-reperfusion can
      induce injury to other organs at the early stage of reperfusion.

PMID- 15447852
TI  - [Screening of differentially expressed genes related to laterally spreading tumor
      by cDNA microarray].
AB  - OBJECTIVE: To screen differentially expressed genes between laterally spreading
      tumor (LST) cell line and common colon carcinoma cell lines, and identify new
      targets and strategies for exploring the pathogenesis of colorectal tumor.
      METHODS: The total RNA was extracted from the LST, SW480 and LoVo cells, from
      which purified mRNAs were obtained. The PCR products of 18 816 genes were blotted
      onto a fibrous membrane to generate the microarray. The mRNAs from the 3 cell
      lines were reversely transcribed into cDNA probes and labeled with (33)P before
      hybridization with the cDNA microarray. After thorough washing, the cDNA
      microarray was scanned and the 3 samples compared. RESULTS AND CONCLUSIONS: A
      series of differentially expressed genes were found between the 3 samples, and 58
      up-regulated and 39 down-regulated genes were identified among the 97
      differentially expressed genes, which suggest different pathogeneses of the
      laterally spreading tumor. Further analysis of the obtained genes can be helpful
      in understanding the molecular mechanism of colorectal tumors.

PMID- 15447853
TI  - [Human complement components C4 and Bf polymorphisms and their complotypes in
      Guangdong Chinese Han population].
AB  - OBJECTIVE: To investigate the genetic polymorphism of human complement components
      C(4) and Bf and their complotype frequencies in Chinese Han population in
      Guangdong Province of China. METHODS: The genetic polymorphisms and complotypes
      of Bf, C(4)A and C(4)B, which were 3 components of HLA-III, were analyzed in 144
      chromosomes of subjects from healthy Han families in Guangdong Province. RESULTS:
      Thirteen variable complotypes were identified, led by the complotypes of S(32),
      S(31), S(42) and F(42) among which strong linkage disequilibria were observed.
      The most common phenotypes were BFS, C(4)A(3), C(4)A(4), C(4)B(2) and C(4)B(1).
      CONCLUSION: The genetic polymorphism of C(4) and Bf and their complotypes have
      their own genetic predisposition in Chinese Han population in Guangdong Province.

PMID- 15447854
TI  - [Diaphyseal defect repair with nacre/polylactic acid composite artificial bone in
      rabbits].
AB  - OBJECTIVE: To evaluate the biocompatibility, degradation and bone formation
      activity of a new bone substitute for bone grafting, nacre/polylactic acid
      composite artificial bone (NPCB). METHODS: Radial bone defects 1.5 cm in length
      were induced in 32 New Zealand rabbits and immediately filled with NPCB or
      nothing. The animals' local and whole body responses to the implants were
      observed after the operation, and the serum calcium levels were detected 1 week
      and 4 weeks postoperatively. Tissue response, new bone formation in the defects
      and degradation of the implants were evaluated by X-ray, and examination of the
      bone mineral content (BMC) in the defects and histomorphological analysis were
      performed after the rabbits were sacrificed. RESULTS: All the rabbits survived
      the operation and the incisions healed smoothly. No significant difference was
      noted in the serum calcium level between 1 day before operation, 1 week and 4
      weeks postoperation. BMC in the defects of the rabbits with NPCB grafts increased
      more rapidly than that in the control group 6-12 weeks after the operation and
      began to decrease after 12 weeks. Gross, X-ray and histological observations
      revealed that NPCB possessed osteoconductive activity and new bone ingrowth in
      the implants was found during the whole experiment. At 16 weeks, the defects
      grafts were almost completely repaired with NPCB while the defects in the control
      group remained nonunion. Biodegradation of the implants was observed early at 6
      weeks, with numerous macrophage and multinuclear giant cells containing
      phagocytosed NPCB particles around the implants at 12 weeks, but NPCB remnants
      were still visible at 16 weeks. CONCLUSION: As a bone substitute, NPCB possesses
      good biocompatibility, biodegradability and osteoconductive activity.

PMID- 15447855
TI  - [An initial examination of the spermatozoal gene expression profile].
AB  - OBJECTIVE: To collect the normal spermatozoal gene expression sequence tags with
      the restriction display technique for constructing a microarray to understand
      spermatozoal gene expression profiles. METHODS: The total RNA extracted from
      normal human spermatozoa were reversely transcribed into cDNAs, which were
      digested by Sau3AI and linked to universal adapters (adapter 1) at both ends.
      According to the sequence of the adapter, a pair of primers (universal primers 1)
      was designed, followed by PCR with primers 1 and the PCR products were
      transferred into E.coli. The positive clones were collected after identification
      to serve as the probes for constructing the gene expression microarray of
      spermatozoa by printing those probes on the slides. The accomplished microarrays
      were examined by Cy3-labeled normal spermatozoal samples. RESULTS: Altogether 1
      859 probes were collected, from which 368 were picked out randomly for
      constructing the microarray. CONCLUSIONS: Human spermatozoa contain a rich
      repertoire of RNAs, and the probes we prepared possess good incredibility and
      speciality.

PMID- 15447856
TI  - [Super SMART cDNA synthesis technology for amplifying small amount of total RNA
      of peripheral blood eosinophils from asthma patients].
AB  - OBJECTIVE: To amplify double-strand cDNA from small amount of total RNA of
      eosinophils from asthma patients by Super SMART cDNA synthesis technique.
      METHODS: The eosinophils were purified from the peripheral blood of asthma
      patients before and after treatment by Percoll gradient centrifugation, from
      which the total RNA was extracted using TRIzol kit. First-strand cDNA synthesis
      and double-strand cDNA amplification were performed using Super SMART cDNA
      synthesis technique. The quality of the obtained cDNA was evaluated by gradient
      cDNA electrophoresis, and the amplification efficiency determined by cDNA
      quantification. RESULT: From 20 ng total RNA, 7.155 microg and 6.568 microg of
      the tester and driver double- strand cDNAs respectively were obtained
      successfully, and the result of electrophoresis indicated high quality and purity
      of the cDNA acquired. CONCLUSION: Super SMART cDNA synthesis technique can
      effectively amplify high-quality double-strand DNA from a very small amount of
      total RNA, which may facilitate the exploration of the mechanism of asthma from
      the genetic level.

PMID- 15447857
TI  - [Hominis placenta promotes melanocyte proliferation  melanin synthesis and
      tyrosinase activity in vitro].
AB  - OBJECTIVE: To investigate the effects of Hominis placenta on melanocytes and
      tyrosinase activity in vitro. METHODS: MTT assay was used to assess the
      proliferation of melanocytes treated with Hominis placenta. Hunt method was
      employed to determine melanin synthesis and the oxidation rate of DL-dopa to
      evaluate the tyrosinase activity. RESULTS: Hominis placenta promoted melanocyte
      proliferation (P<0.01) and significantly increased the cell number (P<0.01),
      melanin synthesis (P<0.01), with the optimal concentration of 0.1g/L (P<0.01),
      and also enhanced tyrosinase activity (P<0.01) at the optimal concentration of 1
      g/L (P<0.01). CONCLUSION: Hominis placenta promotes proliferation, melanin
      synthesis and tyrosinase activity of the melanocytes.

PMID- 15447858
TI  - [Clinical observation of TP regiment for treating refractory and terminal
      squamous cancer of the esophagus].
AB  - OBJECTIVE: To evaluate the therapeutic efficacy and adverse effects of TP regimen
      consisting of taxol (TAX) and cisplatin (DDP) for treating refractory and
      terminal squamous cancer of the esophagus. METHODS: Totally 64 patients with
      stage IV squamous cancer of the esophagus, who failed to respond to a tow-course
      regiment, were treated with TP regimen with intravenous infusion of TAX 175
      mg/m(2) on day 1 and DDP 30 mg/d on days 2-6. After 3 consecutive treatment
      course, each for 28 days, evaluation of the short-term efficacy and adverse
      effects was carried out. RESULTS: All the 64 patients completed altogether 192
      treatment courses of TP regiment, resulting in a total response rate of 59.4%
      including 9 patients with complete remission (CR) and 29 with partial remission
      (PR). Stabilization (SD) was achieved in 12 patients while 14 failed to respond
      favorably and had further progression (PD) of the disease. The median remission
      duration was 4.8 months, median TTP 4.4 months and median survival of 9.8 months
      (4-28 months). The main adverse effect of the regimen was bone marrow depression.
      CONCLUSION: TP regimen for treating refractory and terminal squamous cancer of
      the esophagus is clinically effective and well tolerated.

PMID- 15447859
TI  - [Effects of recombinant Helicobacter pylori catalase on oxidative stress in
      colonic mucosal epithelial cells].
AB  - OBJECTIVE: To investigate the effects of recombinant Helicobacter pylori catalase
      (rHpCAT)on oxidative stress in rat colonic mucosal epithelial cells. METHODS:
      Oxidative stress model was established by hydroxyl generated from Fenton reaction
      in cultured colonic mucosal epithelial cells isolated from normal rats, in the
      model of which the effects of rHpCAT were observed. The cells were divided into
      normal control, model, 5-aminosalicylic acid (5-ASA, 0.1 mmol/L), and rHpCAT (1 x
      10(5), 1 x 10(6), and 1 x 10(7) U/kg, respectively) groups. At the end of the
      experiment, the content of lactic dehydrogenase (LDH), malondialdehyde (MDA),
      myeloperoxidase (MPO), glutathione peroxidase (GSH-Px), catalase (CAT) and,
      superoxide dismutase (SOD) were detected in the culture supernatant. RESULTS: The
      contents of LDH, MDA and MPO were elevated while those of GSH-Px, CAT and SOD
      reduced in the model group. rHpCAT at different doses reduced the release of LDH,
      depressed the contents of MDA and MPO, and increased the contents of GSH-Px, SOD
      and CAT. CONCLUSION: rHpCAT has protective effects against rat colonic mucosal
      oxidative damage.

PMID- 15447860
TI  - [Changes of fasting serum insulin in normotensive patients with left ventricular
      hypertrophy].
AB  - OBJECTIVE: To explore the relationship between left ventricular hypertrophy (LVH)
      and serum insulin changes in normotensive patients. METHODS: Forty-two
      normotensive patients with LVH, who were free of hypertension, coronary artery
      disease and diabetes, were examined for fasting serum insulin, glucose and serum
      lipids, and the left ventricular mass (LVM) and left ventricular mass index
      (LVMI) were also measured with echocardiography, with 46 normal subjects serving
      as the control group. RESULTS: The levels of fasting triglyceride and insulin, as
      well as insulin resistance index (IRI), were higher in the LVH group than in the
      control group. Multifactor regression analysis showed that IRI was positively
      correlated to LVM and LVMI in LVH group (r=0.38, P<0.01; r=0.29, P<0.01).
      CONCLUSION: Hyperinsulinemia is closely correlated with LVH in these normotensive
      patients, and can be involved in the pathogenesis and progression of LVH.

PMID- 15447861
TI  - [Low-dose granulocyte colony-stimulating factor combined with granulocyte
      macrophage colony-stimulating factor for mobilizing peripheral CD34+
      hematopoietic progenitor cells].
AB  - OBJECTIVE: To study the efficacy of combined use of low-dose granulocyte colony
      stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor
      (GM-CSF) in mobilizing hematopoietic stem/progenitor cells. METHODS: Twenty adult
      patients with malignant hematologic diseases were paired using statistical
      methods, and the 10 pairs were divided into 2 equal groups. For non-Hodgkin
      lymphoma, the treatment regimen adopted intravenous infusion of cytoxan (2 g/d
      for 1 or 2 d) and VP16 (0.2 g/d for 1 to 3 d), while for acute non-lymphocytic
      leukemia, Ara-C (2 g/d for 1 to 3 d) and VP16 (0.2 g/d for 1 to 3 d) were used.
      When the while blood cell count (WBC) was below 1.0 x10(9)/L, G-CSF and GM-CSF
      were administered subcutaneously at the same dose of 2.5 microg/d.kg in the 10
      patients in the experimental group, while the patients in the control group
      received only 5 microg/d.kg G-CSF, both for 5 to 6 d. After WBC>5.0 x 10(9)/L,
      the peripheral blood mononuclear cells (PBMNC) were separated by CS-3000 pluse
      separator and CD34+ cells were determined by flow cytometry. RESULTS: The purity
      of the isolated PBMNC was 95%-99%. In the experimental group, the mean number of
      CD34+ cells acquired was 9.4 x 10(6)/kg ranging from 8.4 x 10(6) to 10.2 x
      10(6)/kg, and granulocyte-macrophage colony-forming unit (CFU-GM) was 42.4 x
      10(4)/kg on average ranging from 21.9 x 10(4) to 72.8 x 10(4)/kg, as compared
      with 4.8 x 10(6)/kg [(4.1-8.3) x10(6)/kg] for CD34+ cells and 28.1 x 10(4)/kg
      [(7.1-60.2) x 10(4)/kg] for CFU-GM in the control group (P<0.05). No obvious
      difference was observed between the two groups in terms of the adverse effects of
      the treatment (P>0.05). CONCLUSION: Combined use of G-CSF and GM-CSF can be more
      effective than the exclusive use of GM-CSF for mobilizing CD34+ cells.

PMID- 15447862
TI  - [Remote fetal monitoring for gestational diabetes mellitus].
AB  - OBJECTIVE: To investigate the clinical value of remote fetal monitoring network
      in the antepartum management of gestational diabetes mellitus (GDM). METHODS: Non
      stress test (NST) was preformed in 50 GDM cases by remote electronic fetal
      monitoring network (test group), and another 50 monitored by daily fetal movement
      counting and regular NST check-up in hospital served as the control group.
      Abnormal NST and perinatal outcome were compared between the two groups. RESULTS:
      The incidence of abnormal NST was significantly higher in the test group than in
      the control group (34.6% and 25.5%, P<0.05), as with Apgar scores of the neonates
      between the two groups (9.58+/-0.77 vs 8.70+/-1.23, P<0.01). The incidences of
      neonatal asphyxia (12.0%) and preterm birth (8.0%) in the test group were lower
      than those in the control group (24.0% and 22.0%, respectively, P<0.05). There
      was no significant difference in the rate of cesarean section between the two
      groups (P>0.05). CONCLUSION: Remote fetal monitoring network can be used to
      improve perinatal outcome of GDM, and offers a new option of self-monitoring
      means for pregnant women with GDM.

PMID- 15447863
TI  - [Effect of percutaneous coronary intervention on QT dispersion and its clinical
      implication in patients with acute myocardial infarction].
AB  - OBJECTIVE: To observe the effects of percutaneous coronary intervention (PCI) on
      QT dispersion (QTd) and explore its clinical significance in patients with acute
      myocardial infarction (AMI). METHODS: The electrocardiograms recorded before and
      one day after PCI were analyzed in 138 patients with AMI. The duration from the
      onset of AMI to PCI operation was less than 6 h in 72 patients and 6 to 12 h in
      the other patients. All the patients underwent emergency percutaneous
      transluminal coronary angioplasty and subsequent coronary stenting. QT intervals,
      QTd, and heart rate-corrected QT intervals (QTc) and QTd (QTcd) were measured and
      calculated. RESULTS: In both patient groups receiving PCI with delay shorter and
      longer than 6 h after AMI, QT and QTc after PCI were not significantly different
      from that before PCI, but the QTd and QTcd were remarkably decreased after PCI
      (all the P <0.01). Moreover, the QTd and QTcd in the patients with delay of PCI
      less than 6 h were significantly shorter than those in patients the with greater
      than-6-hour delay (P<0.05), and the inhospital mortality was 4.2% and 7.6% in the
      two groups, respectively (P=0.394). CONCLUSION: Successful PCI may notably reduce
      QTd in the patients with AMI, whose earlier performance usually produces better
      effects.

PMID- 15447864
TI  - [Improvement of suture technique for arteriovenous fistula].
AB  - OBJECTIVE: To investigate the clinical effect of continuous suture technique for
      closure of surgically created arteriovenous fistulas at different sites. METHOD:
      A total of 160 patients with chronic renal failure underwent surgery to create
      arteriovenous fistulas at different sites, which were closed with continuous
      suture technique. RESULTS: The time for vessel anastomosis was reduced with this
      suture technique, and the success rate of anastomosis at one time and the overall
      operative success rate were improved, with also reduction of complications to
      achieve satisfactory clinical results. CONCLUSION: Continuous suture technique
      well suits the demand in anastomosis of arteriovenous fistula at different sites,
      especially in cases with poor vascular condition.

PMID- 15447865
TI  - [Clinical observation of ZD1839 in treating 32 cases of non-small-cell lung
      cancer].
AB  - OBJECTIVE: To study e the therapeutic and adverse effects of ZD1839 in treating
      non-small-cell lung cancer (NSCLC). METHODS: The therapeutic and adverse effects
      of ZD1839 given orally were observed in 32 NSCLC cases after a treatment course
      more than 90 d. RESULTS: The rates of complete remission (CR), partial remission
      (PR), and stabilization (SD) were 0%, 18.75%, and 37.50% respectively, with a
      disease control rate of 56.25%. The adverse effects of this agent included
      acneiform rash, diarrhea, aminotransferase elevation, nausea and vomiting,
      occurring in 31.25%, 18.75%, 12.50% and 15.63% of the cases respectively. No
      interstitial lung disease was found. CONCLUSION: ZD1839 is a new drug producing
      acceptable disease control rate along with tolerable adverse effects in patients
      with lung cancer.

PMID- 15447866
TI  - [Bulbourethral sling for treating urinary incontinence due to intrinsic sphincter
      deficiency].
AB  - OBJECTIVE: To investigate the therapeutic effect of bulbourethral sling for
      treating urinary incontinence resulted from intrinsic sphincter deficiency.
      METHODS: Eighteen male patients with urinary incontinence were treated by
      bulbourethral sling operation. RESULT: In the follow-up for 1 to 34 months, 16
      patients achieved clinical cure and 2 showed significant improvement of the
      symptoms. CONCLUSION: This operation can be effective for treating urinary
      incontinence resulted from intrinsic sphincter deficiency.

PMID- 15447867
TI  - [Age and prognosis: analysis of their association in 93 cases of cervical
      cancer].
AB  - OBJECTIVE: To investigate the relationship between the patient's age and clinical
      prognosis of cervical cancer. METHODS: Ninety-three patients with cervical cancer
      selected from those hospitalized in Nanfang Hospital from Jan 1997 to Dec 2002
      were divided into younger age (less than 35 years old) and elder age group ( more
      than 35 years old). Comparison was made in the clinical stages, pathological
      grade and differentiation between the 2 groups. RESULTS: Statistical difference
      was found in the clinical stages and pathological grade between the 2 groups, and
      in patients below the age of 35 years, 82.61% were below stage II a and 17.39%
      above stage II b, had squamous cell carcinoma and 13.39% had adenocarcinoma; In
      those above 35 years, 51.43% were classified below stage II a stage and 48.73%
      above stage II b, and squamous cell carcinoma were identified in 82.98% and
      adenocarcinoma in 17.02% of these patients. However, no statistical difference
      was found in the cell differentiation between the two groups. CONCLUSIONS:
      Patients above 35 years have poorer prognosis than their younger counterparts,
      which might be due to more advanced clinical stage and higher rate of
      adenocarcinoma.

PMID- 15447868
TI  - [Optimization of the extraction process in the traditional preparation of Baohe
      Wan].
AB  - OBJECTIVE: To study the extraction process for reforming the traditional
      preparation process of Baohe Wan. METHOD: Using the recovery rate of total
      flavonoids of Baohe Wan and pharmacodynamic effects as indices, different
      extraction processes were compared. RESULTS: Supercritical carbon dioxide fluid
      extraction combined with water extraction was optimal for the extraction, and the
      extract prepared by the new process was pharmacodynamically more potent than the
      original Baohe Wan, as demonstrated by the rate of carbon powder moving in the
      small intestine and stomach emptying rate in mice. CONCLUSION: Supercritical
      carbon dioxide fluid extraction combined with water extraction is practical for
      optimizing the preparation of Baohe Wan.

PMID- 15447869
TI  - [Comparison of several silver staining methods for DNA polyacrylamide gel
      electrophoresis].
AB  - OBJECTIVE: To compare 4 silver staining methods for DNA detection in
      polyacrylamide gel electrophoresis. METHODS: After the electrophoresis was
      completed, the gels were stained separately by four different methods, namely
      using ammonia-silver-citric acid, low-concentration silver nitrate, 0.1% and 0.2%
      silver nitrate. RESULTS: DNA was detected only by staining with 0.1% and 0.2%
      silver nitrate. CONCLUSION: 0.2% silver nitrate used along with sodium hydroxide
      shows the highest sensitivity in DNA detection, while its use with sodium
      carbonate produces the best quality of the image.

PMID- 15447870
TI  - [Magnifying endoscope and stereomicroscope in diagnosing colon tumor: experience
      with 139 cases].
AB  - OBJECTIVE: To explore the practical means for identifying early large bowel
      carcinoma and precancerous lesions with magnifying endoscope. METHODS: We
      examined 139 patients with polyp using colonoscopy and mucosal staining, and
      observed the pit patterns (proposed by Kudo) with magnifying endoscope and
      stereomicroscope to identify the relations between the pit patterns and the
      pathologic diagnosis. RESULTS: Polyps were identified in 124 patients and
      advanced cancers in 9. Five laterally spreading tumors (LST) ranging from 10 to
      50 mm in diameter, including 1 of pit IIIL, and 4 of pit IV. were found. The
      findings of the pit patterns by magnifying endoscope were highly consistent with
      those by stereomicroscope in these patients. CONCLUSIONS: Pit patterns are
      crucial to distinguish the cancerous lesions form non-cancerous one and helpful
      for early detection of colorectal cancers. Pit V may serve as warning sign of
      early cancerous lesions.

PMID- 15447871
TI  - [Clinical analyses of complications after ventriculoperitoneal shunt in 125
      cases].
AB  - OBJECTIVE: To review the experience in diagnosis and treatment of postoperative
      complications of ventriculoperitoneal shunt (VPS). METHODS: One hundred and
      twenty-five cases of hydrocephalus undergoing VPS were retrospective analyzed.
      RESULTS: The total incidence of complications was 36.8% in these patients,
      including 24 with shunt block, 9 with infections, 4 with intracranial hematoma, 5
      with abdominal complications and 4 with other complications. CONCLUSIONS:
      Iatrogenic factors, apart from the patient's condition and the nature of disease,
      play an important role in the occurrence of the complications, and careful
      analysis of the causes may help decrease the incidence of the complications.

PMID- 15447872
TI  - [Clinical analysis of 19 elderly patients with displaced proximal humeral two-
      and three-part fractures].
AB  - OBJECTIVE: To analyze the surgical approaches for treating displaced proximal
      humeral two-and three-part fractures in elderly patients. METHODS: Nineteen
      elderly patients with displaced proximal humeral fractures were analyzed,
      including 13 patients with displaced two-part fractures and 6 with displaced
      three-part fractures. All the patients were treated by open reduction and
      fixation with humeral anatomical bone plates. RESULTS: The rate of excellent or
      good healing was 76.9% for two-part fractures without nonunion or humeral head
      necrosis, and was 66.7% for three-part fractures with a rate of humeral head
      necrosis of 16.7%. CONCLUSION: Displaced proximal humeral fractures in elderly
      patients should be managed with minimal open reduction and fixed with humeral
      anatomical bone plate.

PMID- 15447873
TI  - [Different treatments of the middle turbinate and maxillary sinus in endoscopic
      sinus surgery and the curative effect].
AB  - OBJECTIVE: To observe the long-term therapeutic efficacy endoscopic sinus surgery
      with different treatments of the middle turbinate and maxillary sinus. METHODS:
      Endoscopic sinus surgery was performed in 391 patients with chronic sinusitis and
      nasal polypi, who were followed up for 0.5 to 2.5 years postoperatively. RESULTS:
      Of the patients receiving the operation, 328 were cured, 53 showed improvement,
      and 10 failed to respond to the treatment, with a total efficacy rate of 97.5%.
      The major complication of this surgery was nasal cavity adhesion. CONCLUSIONS:
      Appropriate treatment of the middle turbinate and maxillary sinus in endoscopic
      sinus surgery with postoperative comprehensive therapy may enhance the
      therapeutic efficacy and reduce postoperative complications.

PMID- 15447874
TI  - [Hand-assisted laparoscopic partial hepatectomy in the treatment of primary liver
      cancer].
AB  - OBJECTIVE: To explore the techniques of hand-assisted laparoscopic partial
      hepatectomy and its clinical value in the treatment of primary liver cancer.
      METHODS: Six patients with primary liver cancers in the segments II, III, V, VI
      and on the edge of the liver received laparoscopic partial hepatectomy assisted
      by special instruments such as hand-assisted devices, harmonic scalpel, and Endo
      GIA. RESULTS: All of the 6 operations were completed successfully, in which
      resections of both II and III segments, VI segment, and non-regular segment were
      performed. The operative time was 54 to 130 min and postoperative hospital stay 6
      9 days, with intraoperative blood loss of 150-700 ml. No conversion to laparotomy
      was needed, nor did any complications occur. Postoperative follow-up lasted for 6
      to 15 months, during which relapse occurred in 2 cases 3 months and 4 months
      after the operations respectively, while no recurrence has been found in the
      other 4 patients. CONCLUSION: Hand-assisted laparoscopic partial hepatectomy is
      safe and feasible for primary liver cancer in clinically selected patients.

PMID- 15447875
TI  - [Application of laparoscopy in ectopic pregnancy complicated with intrauterine
      pregnancy: reports of 5 cases].
AB  - OBJECTIVE: To investigate the effects of laparoscopy in treating ectopic
      pregnancy complicated with intrauterine pregnancy. METHOD: Laparoscopy was
      performed in 5 patients with ectopic pregnancy complicated with intrauterine
      pregnancy. RESULTS: The ectopic pregnancy tissue or the damaged fallopian tube
      was successfully excised laparoscopically. CONCLUSION: Laparoscopy is safe for
      treating ectopic pregnancy complicated with intrauterine pregnancy, causing
      minimal injuries and less disturbance to intrauterine pregnancy and ensuring
      rapid recovery.

PMID- 15447876
TI  - [Metrorrhagia treated by radio frequency ablation: report of 36 cases].
AB  - OBJECTIVE: To observe the effect of radio frequency ablation (RFA) for treating
      metrorrhagia. METHOD: In-36 metrorrhagia patients, who failed to respond to both
      traditional Chinese medicine and western medicine, and who did not seek child
      bearing with malignant changes of the uterus shown by gynecological examination,
      B-ultrasonic, diagnostic curettage, and pathological examination, the width and
      depth of the uterine cavity were measured while sending the coagulator to the
      bottom of the uterus, followed by coagulation of the uterine cavity for two
      times. The whole process was carried out under the supervision of B-ultrasonic,
      whose strong echo-band was between 0.8 and 1.0 cm. RESULT: Within one year, the
      effective rate was 100%, and no recurrence was found. CONCLUSION: RFA is easy,
      economical, safe and efficient in treating metrorrhagia.

PMID- 15447877
TI  - [Intel random number generator-based true random number generator].
AB  - OBJECTIVE: To establish a true random number generator on the basis of certain
      Intel chips. METHODS: The random numbers were acquired by programming using
      Microsoft Visual C++ 6.0 via register reading from the random number generator
      (RNG) unit of an Intel 815 chipset-based computer with Intel Security Driver
      (ISD). RESULT: We tested the generator with 500 random numbers in NIST FIPS 140-1
      and X(2) R-Squared test, and the result showed that the random number it
      generated satisfied the demand of independence and uniform distribution. We also
      compared the random numbers generated by Intel RNG-based true random number
      generator and those from the random number table statistically, by using the same
      amount of 7500 random numbers in the same value domain, which showed that the SD,
      SE and CV of Intel RNG-based random number generator were less than those of the
      random number table. The result of u test of two CVs revealed no significant
      difference between the two methods. CONCLUSION: Intel RNG-based random number
      generator can produce high-quality random numbers with good independence and
      uniform distribution, and solves some problems with random number table in
      acquisition of the random numbers.

PMID- 15447878
TI  - Maternity and infant care, race and birth outcomes.
AB  - We examine the effect of a large, comprehensive maternity and infant care (MIC)
      program on birthweight and infant mortality in an economically depressed urban
      population. The study is based on linked birth, infant death and program files
      for 1985-87 Cleveland and East Cleveland, Ohio, birth cohorts (N = 31,415).
      Taking into account differences in risk factors, Black MIC infants experienced
      lower neonatal and endogenous mortality, but White MIC infants had higher
      postneonatal and exogenous mortality than their same race, non-MIC counterparts.
      Birthweight distributions were also more favorable for Black than White clients.
      We discuss the policy implications of our findings.

PMID- 15447879
TI  - Assessing predictors of influenza and pneumonia vaccination in rural senior
      adults.
AB  - The overall purpose of this study was to identify predictors of influenza and
      pneumonia vaccination among rural senior adults. A mail survey was conducted in
      eight rural counties. Reported immunization rate for influenza (81.5%) among
      respondents was higher as compared to pneumonia (74.7%). Knowing someone with
      influenza was the strongest predictor of influenza vaccination, and knowing
      someone with pneumonia was the strongest predictor of pneumonia vaccination.
      Belief that vaccinations are always beneficial was also a significant predictor.
      While several of the findings of this study are consistent with factors reported
      in literature to be significant predictors of immunization behavior for this age
      group, surprisingly, access was not a significant predictor for this rural
      sample.

PMID- 15447880
TI  - The utilization and effectiveness of the Family and Medical Leave Act of 1993.
AB  - Since its inception, the Family and Medical Leave Act of 1993 (FMLA) has been a
      source of controversy in American politics. Its enactment allowed leave for
      employees and their family members for serious medical conditions, while
      maintaining their employment status. This study is an exploratory look into the
      utilization and effectiveness of the FMLA for 45 caregivers of children with
      chronic illnesses. Results of a survey indicated that being female (p <.01),
      unmarried (p <.05), and having an annual income less than 35,000 dollars (p
      <.001) have significant negative effects on the eligibility, utilization, and
      effectiveness of the FMLA for caregivers of ill children. The authors argue for
      improved dissemination of FMLA eligibility to employees and employers, and a
      reexamination of the eligibility criteria.

PMID- 15447881
TI  - Policy recommendations for the use of victim-offender mediation to redress
      criminal actions.
AB  - Understanding how to respond effectively and efficiently to crime victims and
      their offenders, and identifying what policies assist victims in having their
      victimization redressed is a major social concern. Social workers have contact
      with these vulnerable populations in many different ways, yet the social work
      profession, in general, is unfamiliar with how to redress victims through
      restorative justice. Restorative justice is an innovative method of viewing
      crime, and a paradigm shift is required when considering the application and
      implication of various forms of restorative justice. It is imperative to keep
      various justice options available, as the effects of crime are detrimental.
      Though reported rates of juvenile and adult crime have decreases during the last
      decade, the costs associated with crime to society remain high. Many victims do
      not report crimes, and if professionals such as medical personnel fail to
      identify crimes, then these costs may be even higher than currently reported.
      Regardless, however, of the costs associated with crime, victims deserve having
      justice evaluated, at least in part, in terms of what they need and want.
      Likewise, it is imperative to evaluate the effects of victim- offender mediation
      (VOM), a form of restorative justice, on offenders as they too deserve potential
      rehabilitation and the chance to redress the harm they caused their victim(s).
      This paper discusses crime effects, provides an overview of VOM, and concludes
      with policy recommendations concerning the use of victim-offender mediation.

PMID- 15447882
TI  - Carbohydrates and the postprandial state: have our cake and eat it too?

PMID- 15447883
TI  - Iron absorption in carriers of the C282Y hemochromatosis mutation.

PMID- 15447884
TI  - Measuring nutritional status in children with chronic kidney disease.
AB  - Children with chronic kidney disease (CKD) are at risk of protein-energy
      malnutrition. Existing clinical practice guidelines recognize this and recommend
      specific methods to assess nutritional status in patients with CKD. This review
      summarizes the methods for nutritional assessment currently recommended in the
      United States for children with CKD and details the strengths and limitations of
      these techniques in the clinical setting. Dietary assessment, serum albumin,
      height, estimated dry weight, weight/height index, upper arm anthropometry, head
      circumference, and the protein equivalent of nitrogen appearance are reviewed. We
      also describe methods for body-composition assessment, such as dual-energy X-ray
      absorptiometry, bioelectrical impedance analysis (BIA), total body potassium,
      densitometry, and in vivo neutron activation analysis, pointing out some
      advantages and disadvantages of each. In CKD, fluid overload is the most
      important factor leading to misinterpretation of nutritional assessment measures.
      Abnormalities in the distribution of fat and lean tissue may also compromise the
      interpretation of some anthropometric measures. In addition, metabolic
      abnormalities may influence the results obtained by some techniques. Issues
      specific to evaluating nutritional status in the pediatric population are also
      discussed, including normalization of nutritional measures to body size and
      sexual maturity. We stress the importance of expressing body-composition measures
      relative to height in a population in whom short stature is highly prevalent.

PMID- 15447885
TI  - Effect of environmental and genetic factors on education-associated disparities
      in weight and weight gain: a study of Finnish adult twins.
AB  - BACKGROUND: Disparities in body mass index (BMI) between persons with different
      educational levels in Western countries are well documented, but the background
      of these education-associated disparities remains poorly understood. OBJECTIVE:
      The objective was to examine the influence of environmental and genetic factors
      on education-associated disparities in self-reported BMI and weight change.
      DESIGN: Longitudinal postal surveys were performed in 1975, 1981, and 1990. The
      data were analyzed by using multivariate genetic models for twin data. The data
      derived from the Finnish Twin Cohort included 2482 monozygotic and 5113 dizygotic
      same-sex male and female twin pairs born between 1915 and 1957. RESULTS:
      Education-associated differences in BMI and in weight change were clear in 1975
      and 1981, respectively, whereas no differences were seen in weight change between
      1981 and 1990 when age and baseline BMI were adjusted for. The trait correlation
      between baseline BMI and educational attainment (-0.15 in men and women) was
      mainly due to correlations between additive genetic factors that contributed to
      BMI and education in men (-0.20; 95% CI: -0.25, -0.14) and women (-0.32; 95% CI: 
      0.40, -0.25) when adjusted for age. Among women, a weaker positive correlation
      was found for the unshared environmental effects contributing to the 2 traits
      (0.06; 95% CI: 0.02, 0.12). The same factors that affected the association
      between education and BMI in 1975 largely explained the association between
      education and weight change in 1981. CONCLUSION: The results suggest the
      possibility that common genetic factors affect educational attainment and body
      weight, which contribute to education-associated disparities in BMI in adulthood.

PMID- 15447886
TI  - Sensory-specific satiety in obese and normal-weight women.
AB  - BACKGROUND: Sensory-specific satiety has been found to play an important role in
      food choice and meal termination, and it might be a factor contributing to
      obesity. OBJECTIVE: We hypothesized that obese and normal-weight people have
      different sensitivities to sensory-specific satiety for high-fat foods. DESIGN:
      Sensory-specific satiety was measured in 21 obese [x body mass index (BMI; in
      kg/m(2)): 33.1] and 23 normal-weight (BMI: 22.8) women who were matched for
      restrained eating behavior, physical activity, age, and smoking behavior. Food
      intake, appetite ratings, and liking scores before and after an ad libitum lunch
      were measured. Products differed in fat content and taste (ie, low-fat sweet, low
      fat savory, high-fat sweet, and high-fat savory), and the subjects tested all 4
      products. In the first study, sandwiches were tested; in the second study, snacks
      were tested. RESULTS: Sensory-specific satiety for all products was observed in
      both subject groups. No significant differences were observed between the obese
      and normal-weight subjects in either sensory-specific satiety or food intake for
      any of the products or product categories tested. Taste (sweet or savory) had a
      significantly (P < 0.05) stronger effect on sensory-specific satiety than did fat
      content. Appetite ratings strongly decreased after lunch, and appetite for a meal
      or snack after lunch was significantly higher in obese than in normal-weight
      subjects, whereas scores before lunch did not differ significantly. CONCLUSIONS:
      Obese and normal-weight people do not differ in their sensitivity to sensory
      specific satiety, and factors other than fat content have the greatest effect on
      sensory-specific satiety.

PMID- 15447887
TI  - The -1131T-->C polymorphism in the apolipoprotein A5 gene is associated with
      postprandial hypertriacylglycerolemia; elevated small, dense LDL concentrations;
      and oxidative stress in nonobese Korean men.
AB  - BACKGROUND: Apolipoprotein A5 plays an important role in modulating
      triacylglycerol metabolism in experimental animal models. OBJECTIVE: The
      objective was to determine associations of the common apolipoprotein A5 gene
      (APOA5) -1131T-->C polymorphism with postprandial lipemic response and other
      cardiovascular disease risk factors in humans. DESIGN: Healthy, nonobese subjects
      [n = 158; mean (+/-SEM) age: 33.8 +/- 1.2 y; body mass index (in kg/m(2)): 23.3
      +/- 0.3] were subdivided into 3 genotype groups: TT (n = 85), TC (n = 56), and CC
      (n = 17). We measured fasting and postprandial lipid concentrations, lipid
      peroxidation, C-reactive protein concentrations, and DNA damage. RESULTS: Fasting
      triacylglycerol concentrations in carriers of the C allele were higher (P < 0.05)
      than in carriers of the TT genotype. No other significant genotype-related
      differences were observed for any of the other baseline measures. After
      consumption of a mixed meal, carriers of the C allele had significantly greater
      increases in total chylomicron and VLDL triacylglycerol than did subjects with
      the TT genotype. Moreover, carriers of the C allele had higher dense LDL, serum C
      reactive protein, and urinary 8-epi-prostaglandin F(2alpha) concentrations and
      more lymphocyte DNA damage. Conversely, we did not find significant genotype
      related differences in postprandial glucose, insulin, or free fatty acid
      measures. CONCLUSIONS: Our data confirm the genetic modulation of serum fasting
      triacylglycerol concentrations by the APOA5 gene polymorphism and extend this
      observation to postprandial triacylglycerol concentrations and to markers of
      oxidation and inflammation. The presence of the C allele in the APOA5 promoter
      region at position 1131 could be a significant factor contributing to higher
      cardiovascular disease risk in Koreans independently of common environmental
      factors.

PMID- 15447888
TI  - Comparison of dietary intakes associated with metabolic syndrome risk factors in
      young adults: the Bogalusa Heart Study.
AB  - BACKGROUND: Previous studies suggested that dietary intakes affect individual
      risk factors associated with metabolic syndrome. OBJECTIVE: The objective of this
      study was to examine dietary intakes in 1181 young adults aged 19-38 y (38.1%
      men; 25% African Americans and 75% whites) in relation to metabolic syndrome risk
      factors in the Bogalusa Heart Study. DESIGN: Participants were stratified into 3
      groups according to the number of risk factors (0, 1-2, >/=3) associated with the
      metabolic syndrome according to the diagnostic criteria of the National
      Cholesterol Education Program, and dietary intakes were compared between the
      groups with a cross-sectional analysis. RESULTS: After adjustment for age, total
      energy intake, body mass index, and physical activity, mean (+/-SE) intakes of
      fruit, fruit juice, and vegetables were significantly higher in subjects who had
      no risk factors than in subjects who had 1-2 risk factors (3.30 +/- 0.09 compared
      with 2.99 +/- 0.07 servings/d; P < 0.05). The mean intake of sweetened beverages
      was lower in subjects who had no risk factors than in subjects who had 1-2 risk
      factors or >/=3 risk factors among whites (1.45 +/- 0.08 compared with 1.77 +/-
      0.07 and 2.22 +/- 0.15 serving/d, respectively, in men; 1.26 +/- 0.06 compared
      with 1.62 +/- 0.05 and 1.78 +/- 0.13 servings/d, respectively, in women; P <
      0.001) but not among African Americans. CONCLUSION: Our results suggest that low
      fruit and vegetable consumption and high sweetened beverage consumption are
      independently associated with the prevalence of metabolic syndrome in specific
      sex-ethnicity populations.

PMID- 15447889
TI  - Effect of interaction between adherence to a Mediterranean diet and the
      methylenetetrahydrofolate reductase 677C-->T mutation on homocysteine
      concentrations in healthy adults: the ATTICA Study.
AB  - BACKGROUND: Dietary and genetic factors may influence the effect of raised
      homocysteine concentrations on coronary artery disease risk. OBJECTIVE: We
      evaluated the effect of the interaction between adoption of a Mediterranean diet
      and the methylenetetrahydrofolate reductase gene (MTHFR) 677C-->T mutation on
      homocysteine concentrations in healthy adults participating in the ATTICA study.
      DESIGN: We studied demographic, lifestyle, clinical, biochemical, and genetic
      information from 322 men (x +/- SD age: 46 +/- 13 y) and 252 women (45 +/- 14 y)
      who had no clinical evidence of cardiovascular or any other chronic disease. We
      also measured total plasma homocysteine concentrations, the distribution of the
      MTHFR genotype, and adherence to a Mediterranean diet. RESULTS: The distribution
      of MTHFR genotypes was as follows: homozygous normal (CC), 41%; heterozygous
      (CT), 48%; and homozygous mutant (TT), 11%. Homocysteine concentrations were
      higher in persons with the TT genotype than in those with the CC and CT genotypes
      (x +/- SD: 15.8 +/- 9 compared with 11.3 +/- 8 and 10.8 +/- 9 micromol/L,
      respectively; P < 0.001). The Mediterranean diet score was not significantly
      associated with homocysteine concentrations (P = 0.89). However, after control
      for potential confounders, the stratified analysis showed that adherence to a
      Mediterranean diet was associated with reduced homocysteine concentrations in
      persons with the TT and CT genotypes (beta = -0.21, P = 0.002, and beta = -0.14,
      P = 0.025, respectively) but not in those with the CC genotype (beta = -0.03, P =
      0.38). CONCLUSION: The observed association of an MTHFR 677C-->T gene-diet
      interaction on homocysteine concentrations may provide a pathophysiologic
      explanation for how a Mediterranean diet may influence coronary risk in persons
      with raised homocysteine concentrations.

PMID- 15447890
TI  - Dietary cholesterol does not increase biomarkers for chronic disease in a
      pediatric population from northern Mexico.
AB  - BACKGROUND: An increased incidence of coronary artery disease (CAD) is prevalent
      in northern Mexico. Effects of specific dietary components on risk factors for
      CAD have not been evaluated in children. OBJECTIVE: The purpose was to evaluate
      the effects of dietary cholesterol provided by whole eggs on the lipoprotein
      profile, LDL size, and phenotype in children from this region. DESIGN: Children
      (29 girls and 25 boys aged 8-12 y) were randomly assigned to either 2 eggs/d (EGG
      period; 518 additional mg cholesterol) or the equivalent amount of egg whites
      (SUB period; 0 additional mg cholesterol) for 30 d. After a 3-wk washout period,
      the children were assigned to the alternate treatment. RESULTS: Subjects were
      classified as hyporesponders (no increase or </=0.05 mmol/L increase in plasma
      cholesterol for 100 mg additional cholesterol) or hyperresponders (>/=0.06 mmol/L
      increase). During the EGG period, the hyperresponders (n = 18) had an elevation
      in both LDL cholesterol (from 1.54 +/- 0.38 to 1.93 +/- 0.36 mmol/L) and HDL
      cholesterol (from 1.23 +/- 0.26 to 1.35 +/- 0.29 mmol/L) with no changes in
      LDL:HDL. In contrast, hyporesponders (n = 36) had no significant alterations in
      plasma LDL or HDL cholesterol. All subjects had an increase in LDL peak diameter
      during the EGG period (P < 0.01) and a decrease (P < 0.01) in the smaller LDL
      subfractions. In addition, 5 of the children having LDL phenotype B (15%) shifted
      from this high-risk pattern to pattern A after the EGG treatment. CONCLUSIONS:
      Intake of 2 eggs/d results in the maintenance of LDL:HDL and in the generation of
      a less atherogenic LDL in this population of Mexican children.

PMID- 15447891
TI  - Associations between coffee consumption and inflammatory markers in healthy
      persons: the ATTICA study.
AB  - BACKGROUND: The effect of coffee consumption on the cardiovascular system is
      conflicting. Inflammation is important to the development of cardiovascular
      disease (CVD), and several dietary factors are thought to exert significant
      effects on inflammation and thus on the risk of CVD. OBJECTIVE: We aimed to
      investigate the associations between coffee consumption and inflammatory markers.
      DESIGN: The cross-sectional survey enrolled 1514 men (x +/- SD age: 46 +/- 13 y;
      range: 18-87 y) and 1528 women (aged 45 +/- 13 y; range: 18-89 y). Five percent
      of men and 3% of women were excluded for history of CVD. Fasting blood samples
      were collected. Dietary habits (including consumption of various types of coffee)
      were evaluated by using a validated food-frequency questionnaire. RESULTS:
      Compared with coffee nondrinkers, men who consumed >200 mL coffee/d had 50%
      higher interleukin 6 (IL-6), 30% higher C-reactive protein (CRP), 12% higher
      serum amyloid-A (SAA), and 28% higher tumor necrosis factor alpha (TNF-alpha)
      concentrations and 3% higher white blood cell (WBC) counts (all: P < 0.05). Women
      who consumed >200 mL coffee/d had 54% higher IL-6, 38% higher CRP, 28% higher
      SAA, and 28% higher TNF-alpha concentrations and 4% higher WBC counts (all: P <
      0.05) than did coffee nondrinkers. The findings were significant even after
      control for the interactions between coffee consumption and age, sex, smoking,
      body mass index, physical activity status, and other covariates. CONCLUSIONS: A
      relation exists between moderate-to-high coffee consumption and increased
      inflammation process. This relation could explain, in part, the effect of
      increased coffee intake on the cardiovascular system.

PMID- 15447892
TI  - Method for estimating body weight in persons with lower-limb amputation and its
      implication for their nutritional assessment.
AB  - BACKGROUND: Body weight is a good indicator of a person's size and is widely used
      in clinical assessment. However, health-status assessment based on observed body
      weight (W(O)) is incorrect for persons with limb amputation. OBJECTIVES: The
      objectives were 1) to develop a more accurate and generalized method for
      estimating body weight in persons with limb amputation, 2) to determine whether
      corrected body weight can be used to assess nutritional status in persons with
      limb amputation, and 3) to test the validity of the estimation by using empirical
      data. DESIGN: Anthropometric data were collected from men from Calcutta and
      adjoining areas with unilateral lower-extremity amputation (n = 102). Mathematic
      formulas were developed for determining estimated body weight (W(E)) and body
      mass index (BMI) calculated from both W(O) and W(E) (ie, BMI(O) and BMI(E),
      respectively). We assessed nutritional status by using BMI(O) and BMI(E) and
      tested the validity of each by considering the result of nutritional assessment
      from midupper arm circumference as the gold standard. We also compared the
      nutritional status results for the subjects with limb amputation with those for a
      similar sample size of healthy control subjects. RESULTS: BMI(E) had a stronger
      association with midupper arm circumference and a higher efficiency (ie,
      proportion of correct results given by any test method) than did BMI(O).
      Moreover, the results obtained with BMI(E) were similar to those obtained with
      BMI in healthy control subjects. However, the nutritional assessments made with
      BMI(O) and BMI(E) did not differ significantly from one another. CONCLUSION: For
      persons with limb amputation, W(E) provides a better basis for appropriate
      nutritional evaluation than does W(O).

PMID- 15447893
TI  - Prediction of daily energy expenditure during a feeding trial using measurements
      of resting energy expenditure, fat-free mass, or Harris-Benedict equations.
AB  - BACKGROUND: During feeding trials, it is useful to predict daily energy
      expenditure (DEE) to estimate energy requirements and to assess subject
      compliance. OBJECTIVE: We examined predictors of DEE during a feeding trial
      conducted in a clinical research center. DESIGN: During a 28-d period, all food
      consumed by 26 healthy, nonobese, young adults was provided by the investigators.
      Energy intake was adjusted to maintain constant body weight. Before and after
      this period, fat-free mass (FFM) and fat mass were assessed by using dual-energy
      X-ray absorptiometry, and DEE was estimated from the change (after - before) in
      body energy (DeltaBE) and in observed energy intake (EI): DEE = EI - DeltaBE. We
      examined the relation of DEE to pretrial resting energy expenditure (REE), FFM,
      REE derived from the average of REE and calculated from FFM [REE = (21.2 x FFM) +
      415], and an estimate of DEE based on the Harris-Benedict equation (HB estimate)
      (DEE = 1.6 REE). RESULTS: DEE correlated (P < 0.001) with FFM (r = 0.78), REE (r
      = 0.73), average REE (r = 0.82), and the HB estimate (r = 0.81). In a multiple
      regression model containing all these variables, R(2) was 0.70. The mean (+/-SEM)
      ratios of DEE to REE, to average REE, and to the HB estimate were 1.86 +/- 0.06,
      1.79 +/- 0.04, and 1.02 +/- 0.02, respectively. CONCLUSIONS: Although a slightly
      improved prediction of DEE is possible with multiple measurements, each of these
      measurements suggests that DEE equals 1.60-1.86 x REE. The findings are similar
      to those of previous studies that describe the relation of REE to DEE measured
      directly.

PMID- 15447894
TI  - Glucose appearance in the peripheral circulation and liver glucose output in men
      after a large 13C starch meal.
AB  - BACKGROUND: Glucose absorption from starchy food has only been described with
      small amounts ingested ( approximately 20-75 g). OBJECTIVE: Our aim was to
      describe total plasma (Ra) and exogenous glucose (Ra(exo)) appearance, glucose
      release from the liver (HGP), and the metabolic response after ingestion of 5 g
      polished or parboiled rice/kg body mass. DESIGN: Gas exchange and urea excretion
      were monitored in 8 healthy subjects before (3.5 h) and after (8 h) ingestion of
      rice intrinsically labeled with (13)C; [6,6-(2)H(2)]glucose was infused for the
      measurement of Ra, Ra(exo), and HGP. RESULTS: Changes in plasma glucose, insulin,
      lactate, and free fatty acids and the increase in Ra(exo) and Ra ( approximately
      200%) and the decrease in HGP ( approximately 90%) were not significantly
      different (P > 0.05) after ingestion of either rice. Glucose oxidation was not
      significantly different (111.6 +/- 8.2 compared with 89.0 +/- 11.3 g; P = 0.13),
      but fat oxidation was significantly lower (9.9 +/- 1.7 compared with 21.3 +/- 4.0
      g; P < 0.05) after parboiled than after polished rice. The percentage of the
      glucose load that appeared in the circulation over 8 h was not significantly
      different after ingestion of polished (70.4 +/- 4.5%) or parboiled (63.8 +/-
      2.0%) rice (P > 0.05). CONCLUSION: Although the starch in parboiled rice is less
      susceptible to digestion in vitro, exogenous glucose availability was not
      significantly different after ingestion of large amounts of polished or parboiled
      rice. Glucose absorption remains incomplete 8 h after ingestion of both types of
      rice.

PMID- 15447895
TI  - Conjugated linoleic acid supplementation, insulin sensitivity, and lipoprotein
      metabolism in patients with type 2 diabetes mellitus.
AB  - BACKGROUND: Some animal studies have suggested that conjugated linoleic acid
      (CLA) supplementation may have therapeutic potential with respect to insulin
      sensitivity and lipid metabolism, which are important cardiovascular disease
      (CVD) risk factors associated with type 2 diabetes mellitus. OBJECTIVE: We
      investigated the effect of CLA supplementation on markers of glucose and insulin
      metabolism, lipoprotein metabolism, and inflammatory markers of CVD in subjects
      with type 2 diabetes. DESIGN: The study was a randomized, double-blind, placebo
      controlled trial. Thirty-two subjects with stable, diet-controlled type 2
      diabetes received CLA (3.0 g/d; 50:50 blend of cis-9,trans-11 CLA and trans
      10,cis-12 CLA) or control for 8 wk. A 3-h 75-g oral-glucose-tolerance test was
      performed, and fasting plasma lipid concentrations and inflammatory markers were
      measured before and after the intervention. RESULTS: CLA supplementation
      significantly increased fasting glucose concentrations (6.3%; P < 0.05) and
      reduced insulin sensitivity as measured by homeostasis model assessment, oral
      glucose insulin sensitivity, and the insulin sensitivity index (composite) (P =
      0.05). Total HDL-cholesterol concentrations increased by 8% (P < 0.05), which was
      due to a significant increase in HDL(2)-cholesterol concentrations (P < 0.05).
      The ratio of LDL to HDL cholesterol was significantly reduced (P < 0.01). CLA
      supplementation reduced fibrinogen concentrations (P < 0.01) but had no effect on
      the inflammatory markers of CVD (C-reactive protein and interleukin 6).
      CONCLUSIONS: CLA supplementation had an adverse effect on insulin and glucose
      metabolism. Whereas CLA had positive effects on HDL metabolism and fibrinogen, a
      therapeutic nutrient should not be associated with potentially adverse effects on
      other clinical markers of type 2 diabetes.

PMID- 15447896
TI  - Glycemic and insulinemic meal responses modulate postprandial hepatic and
      intestinal lipoprotein accumulation in obese, insulin-resistant subjects.
AB  - BACKGROUND: Exacerbated postprandial lipemia is a risk factor for cardiovascular
      disease and is linked to insulin status. Limited data on the effect of dietary
      carbohydrate on postprandial lipoprotein accumulation are available. OBJECTIVE:
      We tested the hypothesis that dietary carbohydrates with different glucose
      availability alter postprandial lipoprotein metabolism differently in obese,
      insulin-resistant subjects. DESIGN: After an overnight fast, 9 subjects with
      central obesity and insulin resistance but normal triacylglycerolemia randomly
      ingested 2 test meals with comparable amounts of fat (28-29 g) and digestible
      carbohydrate (91-94 g) but with different quantities of slowly available glucose
      (SAG) in cereal products (17 or 2 g SAG/100 g for biscuits and wheat flakes,
      respectively). Blood samples were collected before and for 6 h after meal
      intakes. RESULTS: The postmeal 0-2-h areas under the curve (AUCs) for glycemia
      and insulinemia were significantly lower (P < 0.05) after the biscuit meal than
      after the flakes meal. Plasma triacylglycerol concentrations increased
      significantly after the flakes meal but not after the biscuit meal (1.5-fold
      higher 0-6-h AUC for the flakes meal). Apolipoprotein B-100 concentrations in the
      triacylglycerol-rich lipoprotein fraction increased significantly 2 h after the
      flakes meal but not after the biscuit meal (3-fold higher 0-6-h AUC for the
      flakes meal). Apolipoprotein B-48 concentrations increased (P < 0.05) 4 h after
      the flakes meal but not after the biscuit meal (2.3-fold higher 0-6-h AUC for the
      flakes meal). CONCLUSION: Mixed meals containing slowly digestible carbohydrate
      that induces low glycemic and insulinemic responses reduce the postprandial
      accumulation of both hepatically and intestinally derived triacylglycerol-rich
      lipoproteins in obese subjects with insulin resistance.

PMID- 15447897
TI  - Iron and zinc supplementation promote motor development and exploratory behavior
      among Bangladeshi infants.
AB  - BACKGROUND: Iron and zinc deficiency are prevalent during infancy in low-income
      countries. OBJECTIVES: The objectives were to examine whether a weekly supplement
      of iron, zinc, iron+zinc, or a micronutrient mix (MM) of 16 vitamins and minerals
      would alter infant development and behavior. DESIGN: The participants were 221
      infants from rural Bangladesh at risk of micronutrient deficiencies. Development
      and behavior were evaluated at 6 and 12 mo of age by using the Bayley Scales of
      Infant Development II and the Home Observation Measurement of Environment (HOME)
      scale. In this double-blind trial, the infants were randomly assigned to 1 of 5
      treatment conditions: iron (20 mg), zinc (20 mg), iron+zinc, MM (16 vitamins and
      minerals, including iron and zinc), or riboflavin weekly from 6 to 12 mo.
      Multivariate analyses were conducted to examine the change in development and
      behavior for each supplementation group, with control for maternal education,
      HOME score, months breastfed, anemia, growth at 6 mo, and change in growth from 6
      to 12 mo. RESULTS: Iron and zinc administered together and with other
      micronutrients had a beneficial effect on infant motor development. Iron and zinc
      administered individually and in combination had a beneficial effect on
      orientation-engagement. Two-thirds of the infants were mildly anemic, no
      treatment effects on hemoglobin concentration were observed, and hemoglobin was
      not associated with measures of development or behavior. CONCLUSION: The
      beneficial effects of weekly iron and zinc supplementation on motor development
      and orientation-engagement suggest that infants benefit from these minerals when
      administered together.

PMID- 15447898
TI  - Determining bioavailability of food folates in a controlled intervention study.
AB  - BACKGROUND: The concept of dietary folate equivalents (DFEs) in the United States
      recognizes the differences in bioavailability between natural food folates and
      the synthetic vitamin, folic acid. However, many published reports on folate
      bioavailability are problematic because of several confounding factors.
      OBJECTIVE: We compared the bioavailability of food folates with that of folic
      acid under controlled conditions. To broadly represent the extent to which
      natural folates are conjugated in foods, we used 2 natural sources of folate,
      spinach (50% polyglutamyl folate) and yeast (100% polyglutamyl folate). DESIGN:
      Ninety-six men were randomly assigned according to their screening plasma
      homocysteine (tHcy) concentration to 1 of 4 treatment groups for an intervention
      period of 30 d. Each subject received (daily under supervision) either a folate
      depleted "carrier" meal or a drink plus 1) placebo tablet, 2) 200 microg folic
      acid in a tablet, 3) 200 microg natural folate provided as spinach, or 4) 200
      microg natural folate provided as yeast. RESULTS: Among the subjects who
      completed the intervention, responses (increase in serum folate, lowering of
      tHcy) relative to those in the placebo group (n = 18) were significant in the
      folic acid group (n = 18) but not in the yeast folate (n = 19) or the spinach
      folate (n = 18) groups. Both natural sources of folate were significantly less
      bioavailable than was folic acid. Overall estimations of folate bioavailability
      relative to that of folic acid were found to be between 30% (spinach) and 59%
      (yeast). CONCLUSION: Relative bioavailability estimates were consistent with the
      estimates from the metabolic study that were used as a basis to derive the US DFE
      value.

PMID- 15447899
TI  - Determinants of endogenous calcium entry into the gut.
AB  - BACKGROUND: In addition to food sources, calcium enters the gut by way of
      digestive secretions and shed mucosa. In health, such entry is as large as or
      larger than urinary calcium excretion. Because calcium absorption is inefficient,
      most of this endogenous intestinal calcium is excreted. OBJECTIVE: Our aim was to
      determine the dietary, anthropometric, and physiologic determinants of calcium
      entering the digestive stream from endogenous sources. DESIGN: Multiple
      regression modeling of intake and excretion data was used with 553 metabolic
      balance and kinetics studies performed in 190 midlife, white women. RESULTS:
      Endogenous intestinal calcium averaged 3.29 +/- 0.83 mmol/d. Multiple regression
      models explaining variation in this endogenous intestinal calcium were developed
      with use of dietary intake, anthropometric, and serum mineral variables. All 3
      groups of predictor variables individually explained up to 22% of the variation
      in measured values for endogenous intestinal calcium. A composite model,
      incorporating all 3 groups explained 29% of the variation, with phosphorus and
      meat protein intakes, height, weight, and serum calcium and phosphorus
      concentrations all independently entering the model. Phosphorus intake dominated
      over all the other predictors, explaining 20% of the variance all by itself, with
      endogenous intestinal calcium rising by 0.037 mmol for every 1 mmol of phosphorus
      ingested. Meat protein (but not nonmeat protein) was the only other significant
      dietary contributor, exhibiting a negative coefficient. CONCLUSION: As a first
      approximation, the amount of endogenous calcium entering the digestive stream
      rises with body size and with the amount of phosphorus-rich food consumed.

PMID- 15447900
TI  - Iron absorption by heterozygous carriers of the HFE C282Y mutation associated
      with hemochromatosis.
AB  - BACKGROUND: Research conducted before genotyping was possible suggested that
      subjects heterozygous for the genetic mutation associated with hemochromatosis
      absorbed nonheme iron more efficiently than did control subjects when tested with
      a fortified meal. Heme-iron absorption in these subjects has not been reported.
      OBJECTIVE: We compared the absorption of heme and nonheme iron from minimally or
      highly fortified test meals between HFE C282Y-heterozygous and wild-type control
      subjects. DESIGN: After prospective genotyping of 256 healthy volunteers, 11
      C282Y-heterozygous and 12 wild-type control subjects were recruited, and their
      iron absorption was compared by using a hamburger test meal with or without added
      iron and ascorbic acid. After retrospective genotyping of 103 participants in
      previous iron-absorption studies, 5 C282Y-heterozygous subjects were compared
      with 72 wild-type control subjects. RESULTS: HFE C282Y-heterozygous subjects did
      not differ significantly from wild-type control subjects in their absorption of
      either heme or nonheme iron from minimally or highly fortified test meals. No
      differences were detected in blood indexes of iron status (including serum
      ferritin, transferrin saturation, and non-transferrin-bound iron) or in blood
      lipids or transaminases, but heterozygotes had significantly greater, although
      normal, fasting glucose concentrations than did wild-type control subjects.
      Compound heterozygotes (those who had both HFE C282Y and H63D mutations) absorbed
      more nonheme (but not heme) iron from meals with high (but not low) iron
      bioavailability. CONCLUSIONS: HFE C282Y-heterozygous subjects did not absorb
      dietary iron more efficiently, even when foods were highly fortified with iron
      from ferrous sulfate and ascorbic acid, than did control subjects. Iron
      fortification of foods should not pose an additional health risk to HFE C282Y
      heterozygotes.

PMID- 15447901
TI  - Smoking accelerates biotin catabolism in women.
AB  - BACKGROUND: Smoking accelerates the degradation of many nutrients, including
      lipids, antioxidants, and certain B vitamins. Accelerated biotin catabolism is of
      concern in women because marginal biotin deficiency is teratogenic in mammals.
      OBJECTIVE: The objective was to assess the effect of smoking on the biotin status
      of women. DESIGN: A preliminary study of 7 women and 3 men examined the urinary
      concentrations of biotin and its metabolites biotin sulfoxide and bisnorbiotin in
      smokers. The interpretation of the results of this study was limited by the lack
      of a contemporaneous control group; consequently, we conducted a cohort
      controlled study. Smoking women (n = 8) and nonsmoking control subjects (n = 15)
      provided 24-h urine samples; excretion rates of biotin, the biotin metabolites,
      and 3-hydroxyisovaleric acid were determined. Increased urinary excretion of 3
      hydroxyisovaleric acid, which reflects a reduced activity of the biotin-dependent
      enzyme 3-methylcrotonyl-Co A carboxylase, is a sensitive indicator of biotin
      depletion at the tissue level. RESULTS: Compared with control subjects from
      previous studies, the smoking women in the preliminary study excreted
      significantly less urinary biotin (P = 0.02). Moreover, the ratio of urinary
      biotin sulfoxide to biotin increased (P = 0.04) in these women. In the cohort
      controlled study, the urinary excretion of biotin decreased by 30% (P = 0.04),
      and the ratios of urinary bisnorbiotin and biotin sulfoxide to biotin increased
      significantly, which indicated accelerated catabolism in smokers. Moreover, the
      urinary excretion of 3-hydroxyisovaleric acid was greater in the smokers than in
      the control subjects (P = 0.04), which indicated biotin depletion in the smokers
      at the tissue level. CONCLUSION: These data provide evidence of accelerated
      biotin metabolism in smoking women, which results in marginal biotin deficiency.

PMID- 15447902
TI  - Iron in ferritin or in salts (ferrous sulfate) is equally bioavailable in
      nonanemic women.
AB  - BACKGROUND: Recent studies in humans suggest that ferritin iron in soybeans has
      high bioavailability. However, direct evidence for this is lacking because the
      soybeans were intrinsically labeled; thus, iron bound to other ligands, such as
      phytate, was also labeled. OBJECTIVE: The objectives of the study were to
      evaluate the absorption of iron from extrinsically labeled, purified ferritin
      (horse spleen) reconstituted with either high-phosphate iron mineral (plant-type)
      or low-phosphate iron mineral (animal-type) and to compare it with iron
      absorption from ferrous sulfate. DESIGN: Nonanemic, healthy young women were fed
      a standard breakfast meal supplemented with (59)Fe-labeled ferritin or ferrous
      sulfate, in randomized order. Fifteen subjects received ferritin with the low
      phosphate iron mineral, and 15 subjects received ferritin with the high-phosphate
      iron mineral. Iron absorption was measured in a whole-body counter after 14 and
      28 d and by red blood cell incorporation after 28 d. RESULTS: There was no
      significant difference in iron absorption between ferritin and ferrous sulfate:
      low-phosphate iron mineral ferritin (x +/- SD: 21.4 +/- 14.7%) compared with
      ferrous sulfate (21.9 +/- 14.6%), or high-phosphate iron mineral ferritin (22.2
      +/- 19.2%) compared with ferrous sulfate (16.7 +/- 7.1%). Results obtained by
      using whole-body retention of iron and red blood cell incorporation differed with
      the type of iron, which suggests that pathways for iron uptake and utilization
      differed for the 2 forms. CONCLUSIONS: Iron is equally well absorbed from
      ferritin and ferrous sulfate independent of the phosphate content of the ferritin
      iron mineral. Thus, dietary ferritin iron is likely to be a good source of iron.

PMID- 15447903
TI  - Absorption, excretion, and distribution of dietary antioxidant betalains in LDLs:
      potential health effects of betalains in humans.
AB  - BACKGROUND: Betalains were recently identified as natural antioxidants. However,
      little is known about their bioavailability from dietary sources. OBJECTIVE: The
      objective was to evaluate the bioavailability of betalains from dietary sources.
      DESIGN: The plasma kinetics and urinary excretion of betalains were studied in
      healthy volunteers (n = 8) after a single ingestion of 500 g cactus pear fruit
      pulp, which provided 28 and 16 mg indicaxanthin and betanin, respectively. The
      incorporation of betalains in LDL and the resistance of the particles to ex vivo
      induced oxidation was also researched. RESULTS: Betanin and indicaxanthin reached
      their maximum plasma concentrations 3 h after the fruit meal and declined
      according to first-order kinetics. The half-life of betanin (0.94 +/- 0.07 h) was
      shorter than that of indicaxanthin (2.36 +/- 0.17 h). Both compounds had
      disappeared from plasma by 12 h after intake. The urinary excretion of
      indicaxanthin and betanin over 12 h represented 76 +/- 3.0% and 3.7 +/- 0.2%,
      respectively, of the ingested compounds. LDL isolated 3 and 5 h after the fruit
      meal incorporated betalains at concentrations of 100.5 +/- 11 and 50 +/- 7.2
      pmol/mg LDL protein, respectively. In addition, the particles appeared more
      resistant to ex vivo-induced oxidative injury than did the samples isolated
      before fruit ingestion (P < 0.05)-the higher the amount of betalains
      incorporated, the higher the resistance. The concentrations of vitamin E and beta
      carotene in LDL did not change significantly after fruit ingestion. CONCLUSION:
      Our results show that cactus pear fruit is a source of bioavailable betalains and
      suggest that indicaxanthin and betanin may be involved in the observed protection
      of LDL against ex vivo-induced oxidative modifications.

PMID- 15447904
TI  - B-6 vitamers and 4-pyridoxic acid in the plasma, erythrocytes, and urine of
      postmenopausal women.
AB  - BACKGROUND: Although many studies have reported reduced vitamin B-6 status with
      aging, little information is available about the specific effects of menopause.
      OBJECTIVE: We aimed to examine vitamin B-6 metabolism in premenopausal and early
      postmenopausal women. DESIGN: We examined dietary intake and vitamin B-6
      metabolites in the plasma, erythrocytes, and urine of 30 premenopausal women (x
      +/- SD age: 41.9 +/- 4.8 y) and 30 women (aged 54.0 +/- 3.8 y) who were 4.0 +/-
      1.4 y past menopause. RESULTS: Vitamin B-6 intake in the postmenopausal group
      (1.97 +/- 0.40 mg/d) was significantly greater than that in the premenopausal
      group (1.63 +/- 0.50 mg/d). Plasma pyridoxal phosphate (PLP) and pyridoxal
      concentrations and erythrocyte PLP, pyridoxal, and pyridoxamine phosphate
      concentrations were in the normal range in both groups and did not differ
      significantly between the 2 groups. Plasma and erythrocyte 4-pyridoxic acid (4
      PA) concentrations were significantly higher in the postmenopausal group than in
      the premenopausal group, which may have been due at least partly to the slightly
      higher vitamin B-6 intake of the former group. Erythrocyte 4-PA was correlated (r
      = -0.37, P < 0.01) with serum estradiol in both groups. Urinary 4-PA did not
      differ significantly between the 2 groups. The serum phosphate concentration was
      higher in the postmenopausal group than in the premenopausal group, and it was
      correlated (r = 0.40, P < 0.01) with plasma PLP. Inhibition of alkaline
      phosphatase by the increased phosphate may help to increase plasma PLP.
      CONCLUSION: Menopause may not necessarily be associated with a decrease in
      vitamin B-6 status.

PMID- 15447905
TI  - Dual fortification of salt with iodine and micronized ferric pyrophosphate: a
      randomized, double-blind, controlled trial.
AB  - BACKGROUND: In many developing countries, children are at high risk for both
      goiter and anemia. In areas of subsistence farming in rural Africa, salt is one
      of the few regularly purchased food items and could be a good fortification
      vehicle for iodine and iron, provided that a stable yet bioavailable iron
      fortificant is used. OBJECTIVE: We tested the efficacy of salt dual-fortified
      with iodine and micronized ferric pyrophosphate for reducing the prevalence of
      iodine and iron deficiencies in children. DESIGN: In rural northern Morocco, we
      fortified local salt with 25 microg I (as potassium iodate)/g salt and 2 mg Fe
      (as micronized ferric pyrophosphate; mean particle size = 2.5 microm)/g salt.
      After storage and acceptability trials, we compared the efficacy of the dual
      fortified salt (DFS) with that of iodized salt in a 10-mo, randomized, double
      blind trial in iodine-deficient 6-15-y-old children (n = 158) with a high
      prevalence of anemia. RESULTS: After storage for 6 mo, there were no significant
      differences in iodine content or color lightness between the DFS and iodized
      salt. During the efficacy trial, the DFS provided approximately 18 mg Fe/d; iron
      absorption was estimated to be approximately 2%. After 10 mo of treatment in the
      DFS group, mean hemoglobin increased by 16 g/L (P < 0.01), iron status and body
      iron stores increased significantly (P < 0.01), and the prevalence of iron
      deficiency anemia decreased from 30% at baseline to 5% (P < 0.001). In both
      groups, urinary iodine (P < 0.001) and thyroid volume (P < 0.01) improved
      significantly from baseline. CONCLUSION: A DFS containing iodine and micronized
      ferric pyrophosphate can be an effective fortification strategy in rural Africa.

PMID- 15447906
TI  - Hydration of fat-free mass in healthy women with special reference to the effect
      of pregnancy.
AB  - BACKGROUND: Knowledge of the biological variability of the hydration factor (HF),
      ie, the ratio between total body water and fat-free mass, is important when
      calculating total body fat by means of the commonly used two-component model,
      which is based on estimates of body weight and total body water. The effect of
      pregnancy on the biological variability of HF, and consequently on the precision
      of the two-component model, is unknown. OBJECTIVE: Our goal was to assess the
      effect of pregnancy on HF and its biological variability. DESIGN: HF was assessed
      in 33 women planning pregnancy and in 17 of these women during gestational weeks
      14 and 32 and 2 wk postpartum. HF was calculated by using estimates of body
      weight, total body water obtained by means of deuterium dilution, and body volume
      measured by using underwater weighing. RESULTS: In the 17 women who became
      pregnant, HF was 0.718 +/- 0.023, 0.723 +/- 0.031, 0.747 +/- 0.017, and 0.734 +/-
      0.020 before pregnancy, in gestational week 14, in gestational week 32, and 2 wk
      postpartum, respectively. The biological variability represented approximately 2%
      of average HF in the nonpregnant state. The corresponding figure was >3% in
      gestational week 14 but </=1.7% in gestational week 32. CONCLUSION: The two
      component model for assessing body fat is as appropriate during late gestation as
      it is in the nonpregnant state, although its precision may be impaired when
      applied during the first part of pregnancy.

PMID- 15447907
TI  - Relation between hormones and body composition, including bone, in prepubertal
      children.
AB  - BACKGROUND: Sex differences in body composition exist before puberty, but the
      reason for this phenomenon is unknown. The physical changes that occur during
      puberty are mediated, in part, through sex steroids, insulin-like growth factor I
      (IGF-I), and leptin. However, data are lacking that address the extent to which
      concentrations of these hormones influence body composition, bone mass, and
      density in prepubertal children. OBJECTIVE: We investigated the effects of IGF-I,
      dehydroepiandrosterone sulfate, and sex steroids on body composition and fat
      distribution and the effects of these hormones and leptin on total body bone
      mineral content (TBMC) and volumetric bone mineral density (vBMD) at the femoral
      neck and lumbar spine (LS) in 255 healthy children (137 girls), aged 7-8 y.
      DESIGN: Body composition, fat distribution, TBMC, and vBMD were derived by using
      dual-energy X-ray absorptiometry. Association between variables was examined by
      using regression analysis. RESULTS: No sex differences were found in age, height,
      or weight. However, girls had significantly more total body fat, trunk fat, and
      higher LS vBMD but significantly less fat-free soft tissue, TBMC, and femoral
      neck vBMD than did boys. Girls also had significantly (P < 0.001) higher IGF-I,
      estradiol, testosterone, and leptin concentrations than did boys. Estradiol
      concentrations predicted percentage body fat, which supported an effect of
      estrogen on fat storage. Leptin had an independent effect on LS vBMD, which
      suggests a positive effect for leptin on trabecular bone. CONCLUSIONS: The
      hormones examined explained 3-17% of the variations in body-composition measures,
      fat distribution, and bone density, which suggests that other factors are
      important predictors of prepubertal sexual dimorphism.

PMID- 15447908
TI  - Spread fortified with vitamins and minerals induces catch-up growth and
      eradicates severe anemia in stunted refugee children aged 3-6 y.
AB  - BACKGROUND: Multiple micronutrient deficiencies are often the basic causative
      factor in stunting and anemia, 2 conditions that affect entire generations of
      children in deprived populations. No generally accepted recommendations for
      micronutrient intakes for recovery from stunting are available. OBJECTIVE: The
      objective was to assess the effect of a highly nutrient-dense spread fortified
      with vitamins and minerals, with or without antiparasitic metronidazole
      treatment, in correcting retarded linear growth and reducing anemia in stunted
      children. DESIGN: Saharawi refugee children (n = 374) aged 3-6 y with initial
      height-for-age z scores <-2 were assigned to 1 of 5 groups: fortified spread
      (FS), fortified spread plus metronidazole (FS+M), unfortified spread (US),
      unfortified spread plus metronidazole (US+M), or control. Supervised
      supplementation was given daily for 6 mo. Weight, height, knee-heel length,
      hematologic indexes, parasitic infections, and morbidity were assessed at 0, 3,
      and 6 mo. RESULTS: Linear growth of children fed FS was 30% faster at 3 mo than
      in US and control groups, after which height-for-age z scores increased only
      slightly in the FS group and remained unchanged in the other groups. No
      additional benefits from metronidazole were observed. Increase in hemoglobin
      concentrations in the FS group at 6 mo was twofold that in the US and control
      groups (37 +/- 40, 19 +/- 15, and 16 +/- 17 g/L, respectively; P < 0.0001), and
      anemia was reduced by nearly 90%. CONCLUSIONS: FS, and not US, induces catch-up
      growth in stunted children whose diets are poor in micronutrients. Our trial
      provides support for delivering multiple micronutrients to reverse stunting and
      reduce anemia in children up to age 6 y.

PMID- 15447909
TI  - Comparison of the use of body mass index percentiles and percentage of ideal body
      weight to screen for malnutrition in children with cystic fibrosis.
AB  - BACKGROUND: The Cystic Fibrosis Foundation (CFF) recommends using the percentage
      of ideal body weight (%IBW(CFF)) and body mass index percentiles (BMIp) to assess
      weight-for-height status and to screen for malnutrition. OBJECTIVE: The objective
      was to examine the agreement and discrepancy between the use of %IBW(CFF) and
      BMIp for screening malnutrition. DESIGN: Data from 13 021 children reported to
      the 2000 CFF Patient Registry were analyzed. RESULTS: In children of average
      stature (ie, height-for-age between the 25th and 75th percentiles) and aged <10
      y, %IBW(CFF) corresponded closely to BMIp, and the prevalence of underweight
      estimated by %IBW(CFF) < 90% was similar to that by BMIp < 15th percentile.
      However, in children with short stature (ie, height-for-age < 25th percentile),
      %IBW(CFF) reflected significantly better weight-for-height status than did the
      BMIp, whereas the opposite trend was observed in children with tall stature (ie,
      height-for-age > 75th percentile). Such discrepancies averaged 8-12 percentage
      points when BMIp was reexpressed to the same unit and scale as %IBW(CFF).
      Consequently, the prevalence of underweight estimated by %IBW(CFF) < 90% was
      significantly lower (7.3%) than that estimated by BMIp < 15th percentile (25.7%)
      in children with short stature, whereas the opposite trend was found in children
      with tall stature (47.7% and 14.4%, respectively). Additional analyses showed
      that BMIp was more sensitive to, and had stronger associations with, the
      percentage of predicted forced expiratory volume in 1 s. CONCLUSION: Compared
      with BMIp, %IBW(CFF) underestimated the severity of malnutrition in children with
      short stature and overestimated the severity of malnutrition in children with
      tall stature.

PMID- 15447910
TI  - Alcohol intake in relation to brain magnetic resonance imaging findings in older
      persons without dementia.
AB  - BACKGROUND: Consumers of light-to-moderate amounts of alcohol have a lower risk
      of dementia and, possibly, Alzheimer disease than do abstainers. Because vascular
      disease may contribute to symptoms of Alzheimer disease, reduction of
      cerebrovascular disease in consumers of light amounts of alcohol could account
      for that observation. However, a low concentration of alcohol may also have
      direct effects on the hippocampus, a brain structure highly affected by Alzheimer
      disease. OBJECTIVE: We investigated alcohol intake in relation to brain magnetic
      resonance imaging (MRI) findings of presumed vascular origin (ie, white matter
      lesions and infarcts) and findings more specifically found in early Alzheimer
      disease (ie, hippocampal and amygdalar atrophy). DESIGN: In a population-based
      sample of 1074 older persons without dementia (aged 60-90 y), we made brain MRIs
      from which we rated white matter lesions and brain infarcts. In a subset of 509
      people, hippocampal and amygdalar volumes on MRI were measured. Alcohol intake
      was assessed by using a structured questionnaire. We categorized alcohol intake
      as lifetime abstention and very light (<1 drink/wk), light (>/=1 drink/wk to <1
      drink/d), moderate (>/=1 drink/d to <4 drinks/d), and heavy (>/=4 drinks/d)
      intakes. RESULTS: Persons whose alcohol consumption was light to moderate had
      less severe white matter lesions and brain infarcts on MRI than did abstainers or
      heavy drinkers. Abstainers and very light drinkers had smaller hippocampal and
      amygdalar volumes on MRI than did light-to-moderate drinkers, but only if the
      former carried an apolipoprotein (APOE) epsilon4 allele. CONCLUSION: Light-to
      moderate alcohol intake is associated with a lower prevalence of vascular brain
      findings and, in APOE epsilon4 carriers, hippocampal and amygdalar atrophy on
      MRI.

PMID- 15447911
TI  - Effect of age on calcium absorption in postmenopausal women.
AB  - BACKGROUND: It is assumed that calcium absorption decreases with age, but this is
      not well documented. We report a study that addresses this issue. OBJECTIVE: The
      aim was to establish the extent and timing of any age-related change in calcium
      absorption in postmenopausal women. DESIGN: We measured radiocalcium absorption
      (alpha) in 262 healthy postmenopausal women aged 40-87 y. We also measured the
      serum vitamin D metabolites, parathyroid hormone (PTH), and other biochemical
      variables. RESULTS: Radiocalcium absorption decreased with age (P = 0.018); it
      was 28% lower in the 25 women aged >75 y than in the rest (P < 0.001). It was
      significantly related to serum 1,25-dihydroxyvitamin D [1,25(OH)(2)D] in the
      whole set and in both the younger and older subsets, but it was not related to
      either 25-dihydroxyvitamin D [25(OH)D] or PTH or to any other measured variable.
      No decrease in 1,25(OH)(2)D was seen with age to account for the decrease in
      calcium absorption, so radiocalcium absorption corrected for serum 1,25(OH)(2)D
      decreased significantly after age 75 y. On multivariate analysis, the serum
      1,25(OH)(2)D concentration was a positive function of 25(OH)D (P < 0.001),
      albumin (P = 0.010), and PTH (P = 0.012) and a negative function of serum
      creatinine (P = 0.003). PTH was a negative function of calculated ionized calcium
      (P = 0.004) and 25(OH)D (P = 0.009) and a positive function of weight (P = 0.011)
      and age (P = 0.028). CONCLUSIONS: A late age-related decrease in calcium
      absorption is seen in postmenopausal women in addition to the decline that occurs
      at menopause. This decrease could be due to a decline in either the active
      calcium transport or diffusion component of the calcium absorption system.

PMID- 15447912
TI  - Dietary patterns associated with colon and rectal cancer: results from the
      Dietary Patterns and Cancer (DIETSCAN) Project.
AB  - BACKGROUND: An analysis of dietary patterns or combinations of foods may provide
      insight regarding the influence of diet on the risk of colon and rectal cancer.
      OBJECTIVE: A primary aim of the Dietary Patterns and Cancer (DIETSCAN) Project
      was to develop and apply a common methodologic approach to study dietary patterns
      and cancer in 4 European cohorts: the Alpha-Tocopherol Beta-Carotene Cancer
      Prevention Study (Finland-ATBC), the Netherlands Cohort Study (NLCS) on Diet and
      Cancer, the Swedish Mammography Cohort (SMC), and the Ormoni e Dieta nella
      Eziologia dei Tumori (Italy-ORDET). Three cohorts (ATBC, NLCS, and SMC) provided
      data on colon and rectal cancer for the present study. DESIGN: The cohorts were
      established between 1985 and 1992; follow-up data were obtained from national
      cancer registries. The participants completed validated semiquantitative food
      frequency questionnaires at baseline. RESULTS: Exploratory factor analysis,
      conducted within each cohort, identified 3-5 stable dietary patterns. Two dietary
      patterns-Vegetables and Pork, Processed Meats, Potatoes (PPP)-were common across
      all cohorts. After adjustment for potential confounders, PPP was associated with
      an increased risk of colon cancer in the SMC women (quintile 4(multivariate)
      relative risk: 1.62; 95% CI: 1.12, 2.34; P for trend = 0.01). PPP was also
      associated with an increased risk of rectal cancer in the ATBC men (quintile
      4(multivariate) relative risk: 2.21; 95% CI: 1.07, 4.57; P for trend = 0.05).
      Neither pattern was associated with the risk of colon or rectal cancer in the
      NLCS women and men. CONCLUSION: Although certain dietary patterns may be
      consistent across European countries, associations between these dietary patterns
      and the risk of colon and rectal cancer are not conclusive.

PMID- 15447913
TI  - Olive oil, the Mediterranean diet, and arterial blood pressure: the Greek
      European Prospective Investigation into Cancer and Nutrition (EPIC) study.
AB  - BACKGROUND: Diet has been reported to influence arterial blood pressure, and
      evidence indicates that the Mediterranean diet reduces cardiovascular mortality.
      OBJECTIVE: The objective was to examine whether the Mediterranean diet, as an
      entity, and olive oil, in particular, reduce arterial blood pressure. DESIGN:
      Arterial blood pressure and several sociodemographic, anthropometric, dietary,
      physical activity, and clinical variables were recorded at enrollment among
      participants in the Greek arm of the European Prospective Investigation into
      Cancer and Nutrition (EPIC) study. Of these participants, 20 343 had never
      received a diagnosis of hypertension and were included in an analysis in which
      systolic and diastolic blood pressure were regressed on the indicated possible
      predictors, including a 10-point score that reflects adherence to the
      Mediterranean diet and, alternatively, the score's individual components and
      olive oil. RESULTS: The Mediterranean diet score was significantly inversely
      associated with both systolic and diastolic blood pressure. Intakes of olive oil,
      vegetables, and fruit were significantly inversely associated with both systolic
      and diastolic blood pressure, whereas cereals, meat and meat products, and
      ethanol intake were positively associated with arterial blood pressure. Mutual
      adjustment between olive oil and vegetables, which are frequently consumed
      together, indicated that olive oil has the dominant beneficial effect on arterial
      blood pressure in this population. CONCLUSIONS: Adherence to the Mediterranean
      diet is inversely associated with arterial blood pressure, even though a
      beneficial component of the Mediterranean diet score-cereal intake-is positively
      associated with arterial blood pressure. Olive oil intake, per se, is inversely
      associated with both systolic and diastolic blood pressure.

PMID- 15447914
TI  - Fruit and vegetable consumption and bone mineral density: the Northern Ireland
      Young Hearts Project.
AB  - BACKGROUND: Studies examining the relation between bone mineral density (BMD) and
      fruit and vegetable consumption during adolescence are rare. OBJECTIVE: Our
      objective was to determine whether usual fruit and vegetable intakes reported by
      adolescents have any influence on BMD. DESIGN: BMD was measured by dual-energy X
      ray absorptiometry at the nondominant forearm and dominant heel in a random
      sample of 12-y-old boys (n = 324), 12-y-old girls (n = 378), 15-y-old boys (n =
      274), and 15-y-old girls (n = 369). Usual fruit and vegetable consumption was
      assessed by an interviewer-administered diet history method. Relations between
      BMD and fruit and vegetable intake were assessed by using regression modeling.
      RESULTS: Using multiple linear regression to adjust for the potential confounding
      influence of physical and lifestyle factors, we observed that 12-y-old girls
      consuming high amounts of fruit had significantly higher heel BMD (beta = 0.037;
      95% CI: 0.017, 0.056) than did the moderate fruit consumers. No other
      associations were observed. CONCLUSION: High intakes of fruit may be important
      for bone health in girls. It is possible that fruit's alkaline-forming properties
      mediate the body's acid-base balance. However, intervention studies are required
      to confirm the findings of this observational study.

PMID- 15447915
TI  - Plasma folate concentrations are associated with depressive symptoms in elderly
      Latina women despite folic acid fortification.
AB  - BACKGROUND: A relation between low folate status and depression has been
      recognized since the 1960s. Since 1998, flour in the United States has been
      fortified with folic acid, and the prevalence of folate deficiency has decreased
      dramatically. OBJECTIVE: We investigated whether, in this era of folic acid
      fortification, low folate status is a determinant of depressive symptoms in a
      cohort of elderly Latinos (aged >/=60 y) participating in the Sacramento Area
      Latino Study on Aging (SALSA). DESIGN: In a cross-sectional logistic regression
      analysis of data from SALSA (n = 627 M, 883 F), odds ratios (ORs) were
      ascertained for elevated depressive symptoms [Center for Epidemiologic Studies
      Depression Scale (CES-D) score >/=16] among tertiles of plasma folate. Depressive
      symptoms were assessed by using the CES-D. Plasma folate concentrations were
      determined by radioassay. RESULTS: The prevalence of folate deficiency (plasma
      folate </= 6.8 nmol/L) in the SALSA population was <1%. For men, no significant
      association between folate tertile and high CES-D score was observed. The
      adjusted OR for high CES-D score in women in the lowest tertile of folate was
      2.04 (95% CI: 1.38, 3.02), which was significantly different from that in women
      in the highest tertile of folate (P < 0.001). CONCLUSION: These data indicate
      that, despite folic acid fortification, low folate status is associated with
      depressive symptoms in elderly Latina women (but not elderly Latino men).

PMID- 15447916
TI  - Major dietary patterns are related to plasma concentrations of markers of
      inflammation and endothelial dysfunction.
AB  - BACKGROUND: Endothelial dysfunction is one of the mechanisms linking diet and the
      risk of cardiovascular disease. OBJECTIVE: We evaluated the hypothesis that
      dietary patterns (summary measures of food consumption) are directly associated
      with markers of inflammation and endothelial dysfunction, particularly C-reactive
      protein (CRP), interleukin 6, E-selectin, soluble intercellular adhesion molecule
      1 (sICAM-1), and soluble vascular cell adhesion molecule 1 (sVCAM-1). DESIGN: We
      conducted a cross-sectional study of 732 women from the Nurses' Health Study I
      cohort who were 43-69 y of age and free of cardiovascular disease, cancer, and
      diabetes mellitus at the time of blood drawing in 1990. Dietary intake was
      documented by using a validated food-frequency questionnaire in 1986 and 1990.
      Dietary patterns were generated by using factor analysis. RESULTS: A prudent
      pattern was characterized by higher intakes of fruit, vegetables, legumes, fish,
      poultry, and whole grains, and a Western pattern was characterized by higher
      intakes of red and processed meats, sweets, desserts, French fries, and refined
      grains. The prudent pattern was inversely associated with plasma concentrations
      of CRP (P = 0.02) and E-selectin (P = 0.001) after adjustment for age, body mass
      index (BMI), physical activity, smoking status, and alcohol consumption. The
      Western pattern showed a positive relation with CRP (P < 0.001), interleukin 6 (P
      = 0.006), E-selectin (P < 0.001), sICAM-1 (P < 0.001), and sVCAM-1 (P = 0.008)
      after adjustment for all confounders except BMI; with further adjustment for BMI,
      the coefficients remained significant for CRP (P = 0.02), E-selectin (P < 0.001),
      sICAM-1 (P = 0.002), and sVCAM-1 (P = 0.02). CONCLUSION: Because endothelial
      dysfunction is an early step in the development of atherosclerosis, this study
      suggests a mechanism for the role of dietary patterns in the pathogenesis of
      cardiovascular disease.

PMID- 15447917
TI  - Malnourished children and supplementary feeding during the war emergency in
      Guinea-Bissau in 1998-1999.
AB  - BACKGROUND: Supplementary feeding programs (SFPs) are intended to mitigate the
      deterioration of nutritional status and the increase in mortality among
      malnourished children. OBJECTIVE: We investigated the effect of an SFP on
      malnourished children in Guinea-Bissau who were returning to their homes after
      having been displaced within the country because of war in 1998-1999. DESIGN: The
      effect of the war on the nutritional status of children aged 6-59 mo who were
      present in Bissau sometime from September 1998 to June 1999 was evaluated by
      comparing the mortality and the prevalence of malnutrition with the values
      expected had the war not occurred and by comparing the severity of malnutrition
      in malnourished children before and during the war. The quality of the SFP was
      also evaluated. Children with midupper arm circumference < 130 mm were provided
      weekly medical consultations and supplementary feeding until recovery. RESULTS:
      The degree of malnutrition did not increase during the war. The prevalence of
      malnutrition increased with the start of the war but then decreased. The
      mortality of malnourished children did not increase during the war. Seventy-four
      percent of the referred children received treatment; of those, 1% died, 67%
      recovered, and 32% abandoned treatment. Compliance was 89%. The recovery rate was
      13.1. 1000(-1). d(-1), and the median time to recovery was 48 d. Better
      compliance was associated with shorter time to recovery. CONCLUSIONS: Our
      findings may be biased by changes in the cultural and socioeconomic background of
      the malnourished children. However, 3 different analyses indicated a beneficial
      effect of the SFP. Thus, the home-based SFP probably prevented nutritional
      deterioration during the war in Guinea-Bissau.

PMID- 15447918
TI  - Fructose, glycemic load, and quantity and quality of carbohydrate in relation to
      plasma C-peptide concentrations in US women.
AB  - BACKGROUND: Circulating C-peptide concentrations are associated with insulin
      resistance and the development of type 2 diabetes. However, associations between
      fructose and the quantity and quality of total carbohydrate intake in relation to
      C-peptide concentrations have not been adequately examined. OBJECTIVE: We
      assessed the association of dietary fructose, glycemic load, and carbohydrate
      intake with fasting C-peptide concentrations. DESIGN: Plasma C-peptide
      concentrations were measured in a cross-sectional setting in 1999 healthy women
      from the Nurses' Health Study I and II. Dietary fructose, glycemic load, and
      carbohydrate intake were assessed with the use of semiquantitative food-frequency
      questionnaires. RESULTS: After multivariate adjustment, subjects in the highest
      quintile of energy-adjusted fructose intake had 13.9% higher C-peptide
      concentrations (P for trend = 0.01) than did subjects in the lowest quintile.
      Similarly, in the multivariate model, subjects in the highest quintile of
      glycemic load had 14.1% (P for trend = 0.09) and 16.1% (P for trend = 0.04)
      higher C-peptide concentrations than did subjects in the lowest quintile after
      further adjustment for total fat or carbohydrate intake, respectively. In
      contrast, subjects with high intakes of cereal fiber had 15.6% lower (P for trend
      = 0.03) C-peptide concentrations after control for other covariates. CONCLUSIONS:
      Our results suggest that high intakes of fructose and high glycemic foods are
      associated with higher C-peptide concentrations, whereas consumption of
      carbohydrates high in fiber, such as whole-grain foods, is associated with lower
      C-peptide concentrations. Furthermore, our study suggests that these nutrients
      play divergent roles in the development of insulin resistance and type 2
      diabetes.

PMID- 15447919
TI  - Phenotypic expression of the methylenetetrahydrofolate reductase 677C-->T
      polymorphism and flavin cofactor availability in thyroid dysfunction.
AB  - BACKGROUND: The 5,10-methylenetetrahydrofolate reductase gene (MTHFR) 677C-->T
      polymorphism modifies the risk of coronary artery disease and colon cancer and is
      related to plasma concentrations of total homocysteine (tHcy). Riboflavin status
      modifies the metabolic effect of the polymorphism, and thyroid hormones increase
      the synthesis of flavin cofactors. OBJECTIVE: The aim of the study was to
      investigate the phenotypic expression of the MTHFR 677C-->T polymorphism in terms
      of plasma tHcy concentrations in patients with thyroid dysfunction. DESIGN: The
      study population consisted of 182 patients with hyperthyroidism. We studied
      plasma tHcy in relation to MTHFR genotype, riboflavin, and folate before and
      during 6 mo of treatment with antithyroid drugs. RESULTS: Before treatment, tHcy
      was higher in patients with the mutant enzyme than in those with the wild-type
      enzyme. A genotype effect was observed only at low riboflavin or folate
      concentrations (P </= 0.05). During treatment, concentrations of flavin cofactors
      in plasma decreased (P < 0.001), and tHcy increased (P < 0.001). The overall tHcy
      increase was greatest in patients with the T allele, particularly at low
      riboflavin concentrations (P = 0.004). CONCLUSION: Thyroid status affects the
      phenotypic expression of the MTHFR 677C-->T polymorphism, possibly by modifying
      the availability of flavin cofactors.

PMID- 15447920
TI  - The ratio of animal protein intake to potassium intake is a predictor of bone
      resorption in space flight analogues and in ambulatory subjects.
AB  - BACKGROUND: Bone loss is a critical concern for space travelers, and a dietary
      countermeasure would be of great benefit. Dietary protein and potassium
      associated bicarbonate precursors may have opposing effects on the acid-base
      balance in the body and therefore on bone loss. OBJECTIVE: In 2 studies, we
      examined the ability of dietary protein and potassium to predict markers of bone
      metabolism. DESIGN: In the first study, 8 pairs of male identical twins were
      assigned to 1 of 2 groups: bed rest (sedentary, or SED, group) or bed rest with
      supine treadmill exercise in a lower-body negative pressure chamber (EX group).
      In a second study, groups of 4 subjects lived in a closed chamber for 60 or 91 d,
      and dietary data were collected for two or three 5-d sessions. Urinary calcium, N
      telopeptide, and pyridinium cross-links were measured before bed rest; on bed
      rest days 5-6, 12-13, 19-20, and 26-27; and daily during the chamber studies.
      Data were analyzed by Pearson's correlation (P < 0.05). RESULTS: The ratio of
      animal protein intake to potassium intake was significantly correlated with N
      telopeptide in the SED group during bed rest weeks 3 and 4 (r = 0.77 and 0.80)
      and during the 91-d chamber study (r = 0.75). The ratio of animal protein intake
      to potassium intake was positively correlated with pyridinium cross-links before
      bed rest in the EX group (r = 0.83), in the EX group during bed rest week 1 (r =
      0.84), and in the SED group during bed rest week 2 (r = 0.72) but not during
      either chamber study. In both studies, these relations were not significant with
      the ratio of vegetable protein intake to potassium intake. CONCLUSIONS: The ratio
      of animal protein intake to potassium intake may affect bone in ambulatory and
      bed-rest subjects. Changing this ratio may help to prevent bone loss on Earth and
      during space flight.

PMID- 15447921
TI  - Dairy intakes affect bone density in the elderly.
AB  - BACKGROUND: Race and sex differences in the effect of diet on bone mineral
      density (BMD) at the hip in the elderly are unknown. OBJECTIVES: This study
      related cross-sectional nutrient and dairy product consumption to hip BMD in
      white and black men and women aged >60 y and evaluated the influence of nutrient
      and dairy product consumption on changes in BMD in a white cohort participating
      in a calcium, vitamin D, or placebo trial. DESIGN: The Health Habits and History
      Questionnaire was used in 289 white women and 116 white men who participated in
      the trial and in 265 black women and 75 black men to predict total hip and
      femoral neck BMD or changes in BMD. RESULTS: Blacks had higher calcium intakes
      than did whites (700 and 654 mg/d, respectively; P = 0.0094), and men had higher
      calcium intakes than did women (735 and 655 mg/d, respectively; P = 0.0007). For
      men, the correlation between total hip BMD and dairy calcium intake after
      adjustment for age, race, and weight was 0.23 (P < 0.005); this relation was not
      significant in women (r = 0.02, P = 0.12). Similar results were found for femoral
      neck BMD. In the longitudinal study, calcium supplementation reduced bone loss
      from the total hip and femoral neck in those who consumed <1.5 servings of dairy
      products/d and were <72 y old. CONCLUSIONS: Cross-sectional results indicated
      that higher dairy product consumption is associated with greater hip BMD in men,
      but not in women. Calcium supplementation protected both men and women from bone
      loss in the longitudinal study of whites.

PMID- 15447922
TI  - Vitamin K, bone turnover, and bone mass in girls.
AB  - BACKGROUND: Vitamin K has been suggested to have a role in bone metabolism, and
      low vitamin K intake has been related to low bone density and increased risk of
      osteoporotic fracture. OBJECTIVE: The objective of this study was to determine
      whether phylloquinone (vitamin K(1)) intake and biochemical indicators of vitamin
      K status are related to bone mineral content (BMC) and markers of bone formation
      and bone resorption in girls. DESIGN: Vitamin K status [plasma phylloquinone
      concentration and percentage of undercarboxylated osteocalcin (%ucOC)] was
      measured at baseline in a study of 245 healthy girls aged 3-16 y. Cross-linked N
      telopeptide of type 1 collagen (NTx) breakdown, osteocalcin, and bone-specific
      alkaline phosphatase were measured to reflect bone resorption and formation. BMC
      of the total body, lumbar spine, and hip and dietary phylloquinone intake were
      measured annually for 4 y. RESULTS: Phylloquinone intake (median: 45 microg/d)
      was not consistently associated with bone turnover markers or BMC. Better vitamin
      K status (high plasma phylloquinone and low %ucOC) was associated with lower bone
      resorption and formation. Plasma phylloquinone was inversely associated with NTx
      and osteocalcin concentrations (P < 0.05), and %ucOC was positively associated
      with NTx and bone-specific alkaline phosphatase concentrations (P < 0.05).
      Indicators of vitamin K status were not consistently associated with current BMC
      or gain in BMC over the 4-y study period. CONCLUSIONS: Better vitamin K status
      was associated with decreased bone turnover in healthy girls consuming a typical
      US diet. Randomized phylloquinone supplementation trials are needed to further
      understand the potential benefits of phylloquinone on bone acquisition in growing
      children.

PMID- 15447924
TI  - High-fructose corn syrup and the obesity epidemic.

PMID- 15447925
TI  - Update on vitamin A-related deaths in Assam, India.

PMID- 15447927
TI  - Supplementation with zinc and other minerals.

PMID- 15447929
TI  - Polyunsaturated fatty acids and bone mass.

PMID- 15447931
TI  - Discontinuation of salt iodization in children.

PMID- 15447933
TI  - Effect of cow milk consumption on longitudinal height gain in children.

PMID- 15447936
TI  - Alterations in lung mechanics in decorin-deficient mice.
AB  - Decorin, a small leucine-rich proteoglycan with a widespread tissue distribution,
      is required for the normal fibrillogenesis of collagen in most tissues. Because
      collagen is important in determining the elastic behavior of the lung, we
      hypothesized that lung tissue mechanics would be altered in a mutant mouse in
      which the single decorin gene was abrogated by targeted deletion (Dcn-/-).
      Complex impedance of the respiratory system was measured in C57Bl/6 mice (Dcn-/-
      and Dcn+/+) using a small animal ventilator that delivers a volume signal with
      multiple frequencies to the trachea. A constant-phase model was fit to calculate
      airway resistance (R(aw)), tissue damping, and tissue elastance. Compliance of
      the respiratory system (C(rs)) was measured from a pressure volume curve during
      stepwise deflations. Lungs were excised, and parenchymal tissue strips were
      mounted in an organ bath for in vitro measurement of tissue impedance and
      quasistatic length-stress curves. In addition, pulmonary tissue was examined by
      immunohistochemistry and immunoblotting. In vivo, in the Dcn-/- mice, R(aw) was
      decreased and C(rs) was increased. Similarly, in vitro, length-stress curves
      showed increased compliance of the strips in the Dcn-/- mice. These alterations
      in lung tissue mechanical behavior in Dcn-/- mice support a critical role for
      decorin in the formation of the lung collagen network.

PMID- 15447937
TI  - FGF-18 is upregulated in the postnatal rat lung and enhances elastogenesis in
      myofibroblasts.
AB  - The fibroblast growth factors (FGFs) are key players in fetal lung development,
      but little is known about their status in postnatal lung. Here, we investigated
      the expression pattern of FGF-18 transcripts through the perinatal period and
      evidenced a sevenfold increase after birth that paralleled changes in elastin
      expression. In vitro, recombinant human (rh)FGF-18 had a mitogenic activity on
      day 21 fetal rat lung fibroblasts and stimulated its own expression in the
      latter, whereas FGF-2 inhibited it. At 50 or 100 ng/ml, rhFGF-18 increased the
      expression of alpha-smooth muscle actin (alpha-SMA; 2.5-fold), a characteristic
      marker of myofibroblasts, of tropoelastin (6.5-fold), of lysyl oxidase (2-fold),
      and of fibulins 1 and 5 (8- and 2.2-fold) in confluent fibroblasts isolated from
      fetal day 21 lung; similar results were obtained with fibroblasts from day 3
      postnatal lungs. Elastin protein expression was also slightly increased in fetal
      fibroblasts. Lung analysis on day 4 in rat pups that had received rhFGF-18 (3
      microg) on days 0 and 1 showed a 1.7-fold increase of tropoelastin transcripts,
      whereas alpha-SMA transcripts were unchanged. In contrast, rhFGF-2 markedly
      decreased expression of elastin in vitro and in vivo and of fibulin 5 in vitro.
      In addition, vitamin A, which is known to enhance alveolar development, elevated
      FGF-18 and elastin expressions in day 2 lungs, thus advancing the biological
      increase. We postulate that FGF-18 is involved in postnatal lung development
      through stimulating myofibroblast proliferation and differentiation.

PMID- 15447938
TI  - Soluble guanylyl cyclase during postnatal porcine pulmonary maturation.
AB  - The nitric oxide (NO)/cGMP pathway plays a key role in the regulation of
      pulmonary vascular tone during the transition from the fetal to the neonatal
      circulation, and it is impaired in pathophysiological conditions such as
      pulmonary hypertension. In the present study, we have analyzed the changes in the
      function and expression of soluble guanylyl cyclase (sGC) in pulmonary arteries
      during early postnatal maturation in isolated third-branch pulmonary arteries
      from newborn (3-18 h of age) and 2-wk-old piglets. The expression of sGC beta(1)
      subunit in pulmonary arteries increased with postnatal age both at the level of
      mRNA and protein. The catalytic region of porcine sGC beta(1) was sequenced,
      showing a 92% homology with the human sequence. This age-dependent increase in
      sGC expression correlated with increased vasorelaxant responses to the
      physiological sGC activator NO and to the exogenous sGC activator YC-1, but not
      to the membrane-permeable cGMP analog 8-bromoguanosine 3',5'-cyclic
      monophosphate. In conclusion, an increased expression of sGC in pulmonary conduit
      arteries from 2-wk-old compared with newborn piglets explains, at least partly,
      the age-dependent increase in the vasorelaxant response of NO and other
      activators of sGC.

PMID- 15447939
TI  - Freshly isolated rat alveolar type I cells, type II cells, and cultured type II
      cells have distinct molecular phenotypes.
AB  - We used microarray analysis with Affymetrix rat chips to determine gene
      expression profiles of freshly isolated rat type I (TI) and TII cells and
      cultured TII cells. Our goals were 1) to describe molecular phenotypic
      "fingerprints" of TI and TII cells, 2) to gain insight into possible functional
      differences between the two cell types through differentially expressed genes, 3)
      to identify genes that might indicate potential functions of TI cells, since so
      little is known about this cell type, and 4) to ascertain the similarities and
      differences in gene expression between cultured TII cells and freshly isolated TI
      cells. For these experiments, we used preparations of isolated TI and TII cells
      that contained <2% cross-contamination. With a false discovery rate of 1%, 601
      genes demonstrated over twofold different expression between TI and TII cells.
      Those genes with very high levels of differential expression may be useful as
      markers of cell phenotype and in generating novel hypotheses about functions of
      TI and TII cells. We found similar numbers of differentially expressed genes
      between freshly isolated TI or TII cells and cultured TII cells (698, 637 genes)
      and freshly isolated TI and TII cells (601 genes). Tests of sameness/difference
      including cluster dendrograms and log/log identity plots indicated major
      differences between the phenotypes of freshly isolated TI cell and cultured type
      II cell populations. The latter results suggest that experiments with TII cells
      cultured under these conditions should be interpreted with caution with respect
      to biological relevance to TI or TII cells.

PMID- 15447940
TI  - Distinct PKC isoforms mediate cell survival and DNA synthesis in thrombin-induced
      myofibroblasts.
AB  - Thrombin activates protease-activated receptor (PAR)-1 and induces a
      myofibroblast phenotype in normal lung fibroblasts that resembles the phenotype
      of scleroderma lung fibroblasts. We now demonstrate that PAR-1 expression is
      dramatically increased in lung tissue from scleroderma patients, where it is
      associated with inflammatory and fibroproliferative foci. We also observe that
      thrombin induces resistance to apoptosis in normal lung fibroblasts, and this
      process is regulated by protein kinase C (PKC)-epsilon but not by PKC-alpha.
      Overexpression of a constitutively active (c-a) form of PAR-1 or PKC-epsilon
      significantly inhibits Fas ligand-induced apoptosis in lung fibroblasts, whereas
      scleroderma lung fibroblasts are resistant to apoptosis de novo. Thrombin
      translocates p21Cip1/WAF1, a signaling molecule downstream of PKC, from the
      nucleus to cytoplasm in normal lung fibroblasts mimicking the localization of
      p21Cip1/WAF1 in scleroderma lung fibroblasts. Overexpression of c-a PKC-alpha or
      PKC-epsilon results in accumulation of p21Cip1/WAF1 in the cytoplasm. Depletion
      of PKC-alpha or inhibition of mitogen-activated protein kinase (MAPK) blocks
      thrombin-induced DNA synthesis in lung fibroblasts. Inhibition of PKC by
      calphostin or PKC-alpha, but not PKC-epsilon, by antisense oligonucleotides
      prevents thrombin-induced MAPK phosphorylation and accumulation of G(1) phase
      regulatory protein cyclin D1, suggesting that PKC-alpha, MAPK, and cyclin D1
      mediate lung fibroblast proliferation. These data demonstrate that two distinct
      PKC isoforms mediate thrombin-induced resistance to apoptosis and proliferation
      and suggest that p21Cip1/WAF1 promotes both phenomena.

PMID- 15447941
TI  - Increased expression of transient receptor potential vanilloid-1 in airway nerves
      of chronic cough.
AB  - Transient receptor potential vanniloid-1 (TRPV-1) mediates the cough response
      induced by the pepper extract capsaicin and is expressed in sensory nerves that
      innervate the airway wall. We determined the expression of TRPV-1 in the airways
      of patients with chronic persistent cough of diverse causes and with an enhanced
      capsaicin cough response. We obtained airway mucosal biopsies by fiberoptic
      bronchoscopy in 29 patients with chronic cough and 16 healthy volunteers without
      a cough. Immunostaining for nerve profiles with anti-protein gene product (PGP)
      9.5 antibody showed no increase in nerve profiles in the airway epithelium of
      patients with chronic cough; however, with an anti-TRPV-1 antibody, there was a
      fivefold increase of TRPV-1 staining nerve profiles (p < 0.001). There was a
      significant correlation between capsaicin tussive response and the number of TRPV
      1-positive nerves within the patients with cough. Our findings indicate that TRPV
      1 receptors may contribute to an enhanced cough reflex and the cough response in
      chronic persistent cough of diverse causes.

PMID- 15447942
TI  - Alveolar epithelial beta 2-adrenergic receptors: their role in regulation of
      alveolar active sodium transport.

PMID- 15447943
TI  - Non-mannose-capped lipoarabinomannan induces lung inflammation via toll-like
      receptor 2.
AB  - Non-mannose-capped lipoarabinomannan (AraLAM) is part of the cell membrane of
      atypical mycobacteria. To determine the capacity of AraLAM to induce lung
      inflammation in vivo and to determine the signaling receptors involved herein,
      wild-type (WT) mice, lipopolysaccharide binding protein knockout mice, CD14
      deficient (CD14 KO) mice, Toll-like receptor (TLR) 4 mutant mice, or TLR2 KO mice
      were intranasally inoculated with purified AraLAM. AraLAM induced high lung
      levels of tumor necrosis factor, interleukin-1beta, interleukin-6, and cytokine
      induced neutrophil chemoattractant (KC) and an influx of neutrophils into the
      pulmonary compartment of WT mice. Lipopolysaccharide binding protein knockout,
      CD14 KO, and TLR4 mutant mice displayed similar inflammatory responses as WT
      mice, whereas in TLR2 KO mice, AraLAM-induced lung inflammation was strongly
      diminished. In addition, TLR2 KO mice, but not CD14 KO or TLR4 mutant mice,
      displayed a delayed clearance of pulmonary infection with the atypical AraLAM
      expressing Mycobacterium smegmatis. These data indicate that TLR2 is the
      signaling receptor for purified AraLAM in the lung in vivo and that this receptor
      contributes to an effective clearance of M. smegmatis from the pulmonary
      compartment.

PMID- 15447944
TI  - Angiotensin-converting enzyme, sleep-disordered breathing, and hypertension.
AB  - The angiotensin-converting enzyme (ACE) gene insertion/deletion polymorphism
      influences ACE activity, cardiovascular risk, blood pressure, and possibly the
      risk of developing Alzheimer's dementia. We explored the association of the
      insertion/deletion polymorphism with sleep-disordered breathing (SDB) and
      hypertension in 1,100 subjects of the Wisconsin Sleep Cohort. The polymorphism
      did not influence body mass index or the occurrence of SDB, but was dose
      dependently associated with blood pressure. Interestingly, SDB and the
      insertion/deletion polymorphism interacted significantly to modulate blood
      pressure independently of age, sex, ethnicity, and body mass index. Most
      specifically, the association of the deletion allele with hypertension was most
      pronounced in subjects with mild to moderate degrees of sleep apnea (5 < or =
      apnea-hypopnea index < or = 30). We hypothesize that in the absence of SDB the
      effect of the deletion allele alone may not be sufficient to increase blood
      pressure. At severe levels of SDB, the effect of sleep apnea on blood pressure
      overwhelms any association of the deletion allele with hypertension and occurs
      independent of any ACE gene genotype.

PMID- 15447945
TI  - Allergen exposure of mouse airways evokes remodeling of both bronchi and large
      pulmonary vessels.
AB  - Remodeling of airway structures is a well-documented feature of allergic airway
      inflammation. To investigate whether bronchial remodeling is associated with
      remodeling of adjacent pulmonary vessels, sensitized mice were subjected to
      repeated ovalbumin inhalations, and bronchi and pulmonary vessels were subjected
      to histologic analysis. Allergen challenges induced peribronchial as well as
      perivascular eosinophilia. Remodeling of systemic airway microcirculation, as
      studied in tracheal whole-mount preparations, revealed an allergen-induced
      increase in both the diameter and length of the airway microvessels.
      Immunostaining for alpha-smooth muscle actin disclosed an increase in smooth
      muscle mass in both bronchi and large pulmonary vessels. Both bronchi and
      pulmonary vessels also displayed increased expression of procollagen I and
      procollagen III. Staining for proliferating cell nuclear antigen revealed
      increased proliferation of bronchial epithelial and smooth muscle cells as well
      as pulmonary vascular endothelial and smooth muscle cells. We conclude that
      central features of remodeling that take place in allergen-exposed airways are
      present also in the pulmonary vessels. The significance of this finding with
      respect to occurrence in disease, pathophysiologic importance, and involved
      mechanisms warrants further investigation.

PMID- 15447947
TI  - Procalcitonin kinetics as a prognostic marker of ventilator-associated pneumonia.
AB  - We investigated the value of procalcitonin kinetics as a prognostic marker during
      ventilator-associated pneumonia (VAP). This prospective, observational study was
      conducted in a medical intensive care unit in a university hospital. All
      consecutive patients with microbiologically proven VAP who survived 3 days after
      its diagnosis were included and grouped according to clinical outcome: favorable
      or unfavorable, defined as death, VAP recurrence, or extrapulmonary infection
      requiring antibiotics before Day 28. Serum procalcitonin levels were measured on
      Days 1, 3, and 7 for all patients. Among the 63 patients included, 38 had
      unfavorable outcomes. On Day 1, they were more critically ill than patients with
      a favorable outcome. Serum procalcitonin levels decreased during the clinical
      course of VAP but were significantly higher from Day 1 to Day 7 in patients with
      unfavorable outcomes. Multivariate analyses retained serum procalcitonin levels
      on Days 1, 3, and 7 as strong predictors of unfavorable outcome. Based on these
      data, procalcitonin could be a prognostic marker of outcome during VAP.

PMID- 15447946
TI  - Airway responses to aerosolized brevetoxins in an animal model of asthma.
AB  - Florida red tide brevetoxins are sodium channel neurotoxins produced by the
      dinoflagellate Karenia brevis. When aerosolized, the toxin causes airway symptoms
      in normal individuals and patients with airway disease, but systematic exposures
      to define the pulmonary consequences and putative mechanisms are lacking. Here we
      report the effects of airway challenges with lysed cultures of Karenia brevis
      (crude brevetoxin), pure brevetoxin-2, brevetoxin-3, and brevetoxin-tbm
      (brevetoxin-2 minus the side chain) on pulmonary resistance and tracheal mucus
      velocity, a marker of mucociliary clearance, in allergic and nonallergic sheep.
      Picogram concentrations of toxin caused bronchoconstriction in both groups of
      sheep. Brevetoxin-tbm was the least potent, indicating the importance of the side
      chain for maximum effect. Both histamine H(1)- and cholinergic-mediated pathways
      contributed to the bronchoconstriction. A synthetic antagonist, beta-naphthoyl
      brevetoxin-3, and brevenal, a natural antagonist, inhibited the
      bronchoconstriction. Only crude brevetoxin and brevetoxin-3 decreased tracheal
      mucus velocity; both antagonists prevented this. More importantly, picomolar
      concentrations of the antagonists alone improved tracheal mucus velocity to the
      degree seen with mM concentrations of the sodium channel blocker amiloride. Thus,
      Karenia brevis, in addition to producing toxins that adversely affect the
      airways, may be a source of agents for treating mucociliary dysfunction.

PMID- 15447948
TI  - Are inhaled corticosteroids systemic therapy for chronic obstructive pulmonary
      disease?

PMID- 15447949
TI  - Snoring and passive smoking--a counterblaste?

PMID- 15447950
TI  - Hunger disease and pulmonary alveoli.

PMID- 15447951
TI  - Macromolecular interactions and ion transport in cystic fibrosis.
AB  - Cystic fibrosis (CF) is a genetic disease caused by autosomal recessive mutations
      of the CF transmembrane regulator, CFTR. CFTR functions in the plasma membrane of
      epithelial cells lining the lung, pancreas, liver, intestines, sweat duct, and
      the epididymis. The primary problem in CF is that mutations in CFTR affect its
      ability to be made, processed, and trafficked to the plasma membrane and/or its
      function as a Cl(-) channel and conductance regulator. Many proteins and
      processes normally interact with normal CFTR throughout its life cycle and mutant
      CFTR during the disease process. Understanding the function of these proteins and
      processes is expected to provide a clearer understanding of how normal CFTR is
      involved in salt movement and how mutant CFTR is handled by the cell and leads to
      the pathophysiology of CF. Recently, efforts to find therapies that correct
      defective CFTR have been intensifying. To facilitate our understanding of normal
      and mutant CFTR and the identification of new drug targets for developing novel
      therapies, a panel of experts was convened by the National Heart, Lung, and Blood
      Institute to explore the critical questions, challenges, and current
      opportunities to highlight new areas of research that would facilitate a
      integrated understanding of the processes and proteins that impact CFTR. The
      meeting highlighted the multiple pathways and interacting proteins involved in
      CFTR folding and biosynthesis, processing, and trafficking. A number of critical
      areas for future study were identified. Although these therapies are promising, a
      big question remains as to whether simply correcting defective CFTR will lead to
      significant improvement in patient health or whether the symptoms manifested in
      CF will require therapies in addition to those that target defective CFTR
      specifically.

PMID- 15447952
TI  - Smoking is not beneficial for tuberculosis.

PMID- 15447954
TI  - Mortality rates and self reported health: database analysis by English local
      authority area.

PMID- 15447955
TI  - Liver ablation therapy.

PMID- 15447956
TI  - Cytomegalovirus pneumonia after bone marrow transplantation: high resolution CT
      findings.
AB  - Cytomegalovirus (CMV) pneumonia is one of the most common pulmonary complications
      after bone marrow transplantation (BMT). We describe the high resolution CT
      (HRCT) findings of 13 patients with CMV pneumonia diagnosed after allogenic BMT.
      The study included 13 consecutive patients who developed CMV pneumonia after BMT
      and who had HRCT of the chest performed within 24 h of the onset of symptoms.
      HRCT scans were reviewed by two radiologists who assessed pattern and
      distribution of findings. There were nine male and four female patients, ranging
      from 9 years to 56 years of age (mean age 33 years). BMT was performed for
      treatment of chronic myelogenous leukaemia (54%), severe aplastic anaemia (23%),
      acute myelogenous leukaemia (15%) and Fanconi's anaemia (8%). The time elapsed
      until diagnosis ranged from +18 days to +405 days (median of 54 days, mean +81.6
      days). The predominant patterns of abnormality on HRCT scans were ground-glass
      opacities (69%), small centrilobular nodules (69%) and air-space opacities (54%).
      The abnormalities were distributed in the central and peripheral zones of the
      lungs in six cases, only in the periphery in four cases, and only in the central
      zone in three cases. In all cases the lung lesions were bilateral, and asymmetry
      was observed in seven cases. The authors conclude that the most common HRCT
      findings in patients with CMV pneumonia after BMT consist of bilateral asymmetric
      ground-glass, air-space opacities and small centrilobular nodules.

PMID- 15447957
TI  - Quantitative measurement of hepatic portal perfusion by multidetector row CT with
      compensation for respiratory misregistration.
AB  - Our purpose was to determine whether hepatic portal perfusion assessed by
      multidetector row CT using compensation for respiratory misregistration can
      predict the severity of chronic liver disease. We carried out dynamic CT in 43
      patients (chronic hepatitis: n=9; cirrhosis: n=24; normal liver: n=10). In this
      series, 20 patients had liver tumours. The CT protocol was designed to avoid
      respiratory artefacts and included two interscan breathing periods during the
      study. To compensate for respiratory misregistration, image sets in the same z
      axis position were acquired from four-slice data on each scan, and the portal
      perfusion calculations were made according to the maximum slope method. Portal
      perfusion was compared with and without compensation for respiratory
      misregistration, and the different types of hepatic disease. In the liver tumour
      patients in particular, portal perfusion was compared with the degree of hepatic
      fibrosis in the liver sections. Portal perfusion in the patients without
      compensation for respiratory misregistration (1.10 ml min(-1)ml(-1)) was higher
      than that of those with compensation (0.99 ml min(-1)ml(-1); p=0.036). Hepatic
      portal perfusion of patients with chronic hepatitis (0.97 ml min(-1)ml(-1)) and
      liver cirrhosis (0.88 ml min(-1)ml(-1)) was less than that of patients with
      normal liver (1.32 ml min(-1)ml(-1); p=0.03, 0.001). Moderate correlation was
      seen between portal perfusion and the percentage of fibrosis in patients with
      liver tumours (r=0.55). Hepatic portal perfusion obtained by multidetector row
      dynamic CT using compensation for respiratory misregistration has the potential
      to improve non-invasive assessment of the degree of chronic liver disease.

PMID- 15447958
TI  - Reference level for patient dose in dental skull lateral teleradiography.
AB  - The present work describes an experiment to obtain a local reference dose value
      in lateral skull teleradiography for dental applications. The reference value was
      based on patient measurements in seven dental X-ray units, using
      thermoluminescent chips, and measurements on a rubber globe filled with water at
      another 78 installations. Dosemeters were located initially in the head and neck
      of a human phantom to select the most suitable locations, and on the cephalostat
      of the X-ray unit at two appropriate locations, which did not interfere with the
      patient or with the usual imaging routine. The skin projection of the Porion
      point was considered the best position. 523 patients were monitored in the seven
      units; then patient doses and dose values from measurements on rubber balloons
      were compared to normalize and combine the data. The provisional reference value
      proposed is 400 microGy.

PMID- 15447959
TI  - Normative data for ultrasound measurement of the calcaneus within different
      female ethnic groups.
AB  - The purpose of this study was to generate normative broadband ultrasound
      attenuation data for UK resident Indian-Asian, African-Caribbean and Chinese
      women, aged 20-80 years, using the McCue Cubaclinical II device. Additionally,
      comparisons were made against available Caucasian data previously collected by
      the authors. Exclusions were: use of hormone replacement therapy, corticosteroids
      or thyroxine for more than 6 months; menopause before the age of 45 years;
      oophrectomy; lactation within the preceding year; rheumatoid arthritis or a
      previous osteoporotic fracture. 977 women were recruited from various community
      centres, from a local GP surgery and from university colleges in the London area.
      Broadband ultrasound attenuation and velocity of sound were determined for the
      left and right os calces. Repeat measures on each side after re-positioning, to
      allow for anatomical variation, were averaged. Significance was set at a minimum
      level of 0.05. There were significant differences in non-dominant and dominant
      measures in all ethnic groups except African-Caribbean. For comparison purposes
      the means of the non-dominant measurements were plotted against age using a
      polynomial model to give the best data fit. No significant difference was found
      between non-dominant broadband ultrasound attenuation measurements for either
      Asian or Chinese when compared with the Caucasian sample populations. A
      significant difference in broadband ultrasound attenuation was found between
      African-Caribbean and Caucasian, with African-Caribbean between 10% (age group 20
      30 years) and 29% (age group 70-80 years) higher. There was no significant
      difference in body mass index between Caucasian and Chinese groups, but
      significant differences were found between Caucasian and Asian, and between
      Caucasian and African-Caribbean groups.

PMID- 15447960
TI  - Considerations on the measurement of practical peak voltage in diagnostic
      radiology.
AB  - An evaluation of the non-invasive measurement of the practical peak voltage (PPV)
      in the quality control of X-ray units used in diagnostic radiology was carried
      out. Two instruments were employed: the PTW Diavolt Universal Tester with
      readings in PPV and the Waveform Tester for X-rays (WATEX) prototype proposed
      here, which uses a PIN structure (P-type diffusion, Intrinsic region, N-type
      diffusion) photodiode as a sensor. The reference for the measurements was the
      voltage signal obtained in an oscilloscope from an invasive high voltage divider
      in order to verify the accuracy and precision of the measurements. The readings
      of the PPV in the Diavolt show a systematic error between 1% and 8%, always being
      less than the real value. An explanation for this difference is proposed, based
      on the relation between the effect of the X-rays in the film and the response of
      the sensor to the product of the applied voltage to the X-ray tube (peak voltage
      kVp), and the anode current. This explanation was confirmed using the WATEX
      waveform tester.

PMID- 15447961
TI  - Threshold contrast detail detectability curves for fluoroscopy and digital
      acquisition using modern image intensifier systems.
AB  - Threshold contrast detail detectability (TCDD) test objects are a commonly used
      tool to assess image quality of imaging systems. FAXIL (The Facility for the
      Assessment of X-ray imaging, Leeds) produced updated standard TCDD curves, for
      fluoroscopy systems in good adjustment, in 1992. Fluoroscopy curves can be
      corrected to account for the effect of image intensifier input air kerma rate and
      field size. This paper presents updated TCDD curves for fluoroscopy and new
      curves for digital acquisition. The results for digital acquisition suggest that
      the TCDD curves should not be corrected for input air kerma, as the quantum noise
      is not dominant and system noise is significant. These curves will prove useful
      for accepting new equipment, to give an indication of the expected image quality
      for a new image intensifier system.

PMID- 15447962
TI  - Ultrasound measured renal length versus low dose CT volume in predicting single
      kidney glomerular filtration rate.
AB  - Ultrasound measured renal length and CT measured renal volume are potential
      surrogate markers for single kidney glomerular filtration rate (SKGFR). The aims
      of this study are to determine: (1) the repeatability of ultrasound measured
      length and low radiation dose spiral CT measured volume; (2) the relationship
      between renal length and volume; and (3) whether length and/or volume is a
      predictor of SKGFR. 69 patients with suspected renal artery stenosis underwent
      ultrasound renal length measurement, CT evaluation of renal volume and assessment
      of SKGFR. 40 patients had ultrasound measurement of length and CT evaluation of
      volume performed twice on two separate visits. 25 patients also had ultrasound
      measured renal parenchymal thickness and area. The region of interest was drawn
      around the kidneys and a threshold set to subtract renal peripelvic fat and renal
      pelvis. The volume from each slice was summed to obtain the total volume for each
      kidney. The limits of agreement for ultrasound measured renal length were -1.6 cm
      to 1.52 cm and that for CT renal volume were -33 ml to 32 ml. There was
      significant correlation between ultrasound measured length and CT volume (r=0.74,
      p<0.01). Volume was a better predictor of SKGFR (r(2)=0.57) than length
      (r(2)=0.48). The combined parameters of ultrasound measured length, area and
      parenchymal thickness were a better predictor of volume (r(2)=0.81) and SKGFR
      (r(2)=0.58) than ultrasound measured length on its own. The low dose CT technique
      was reasonably reproducible and renal volume measurements correlate better with
      SKGFR than length. Ultrasound predictions of renal volume and SKGFR can be
      improved by incorporating cross-sectional area and parenchymal thickness. Further
      investigation is required to refine our low dose CT technique.

PMID- 15447963
TI  - Determination of the optimum dose per fraction in fractionated radiotherapy when
      there is delayed onset of tumour repopulation during treatment.

PMID- 15447964
TI  - A comparison of conventional, conformal and intensity-modulated coplanar
      radiotherapy plans for posterior fossa treatment.
AB  - Radiotherapy of the posterior fossa for medulloblastoma treatment can induce
      ototoxicity, especially when combined with cisplatin chemotherapy. Sensorineural
      hearing loss can be severe enough to cause permanent disability, which may
      compromise cognitive development in paediatric patients. This study evaluates the
      sparing of the cochlea in conventional radiotherapy, three-dimensional conformal
      radiotherapy (3D-CRT), and intensity-modulated radiotherapy (IMRT). CT scans of
      three patients were used to plan posterior fossa radiotherapy using coplanar beam
      arrangements. The posterior fossa and the cochlea were contoured as well as other
      organs-at-risk (non-posterior fossa brain, lenses, optic nerves, pituitary and
      cervical spinal cord). Three treatment plans were compared: conventional two
      dimensional treatment (parallel-opposed lateral pair); 3D-CRT (two wedged
      posterior oblique fields); and a four-field coplanar IMRT plan. 3D-CRT and IMRT
      reduced cochlear doses to less than 70% of the mean target dose. These plans also
      reduced dose to the non-posterior fossa brain and cervical spinal cord. IMRT
      showed no advantage over 3D-CRT in sparing the optic nerves and lenses, compared
      with 3D-CRT. Normal tissue doses were higher in both conformal techniques than in
      the IMRT plans. Conformal techniques reduced the dose to the cochlea, non
      posterior fossa brain and cervical spinal cord. The small size and proximity to
      the planning target volume (PTV) of the cochlea limited the effectiveness of the
      IMRT plan. Coplanar 3D-CRT was judged superior to coplanar IMRT, particularly in
      children, because it achieved adequate sparing of the cochlea and anterior
      cranial structures, such as the lenses and optic nerves, without compromising the
      dose to the posterior fossa.

PMID- 15447965
TI  - Training improves medical student performance in image interpretation.
AB  - The aim of this study was to objectively quantify the effects of radiological
      teaching on student performance in interpreting radiological images, and to
      establish whether training location affects performance. 114 clinical students
      were asked to anonymously interpret radiological cases before and after 26 weeks
      clinical training. Improvements were assessed by comparing performance on the
      median question in each assessment using the Kruskal-Wallis analysis. Variations
      according to different placements were assessed by the Mann-Whitney U-test. There
      was a highly significant (p<0.001) improvement in the performance of the group
      with training. The proportion of correct answers to the median question improved
      from 8% to 43%. Differences between training placements were non-significant. Our
      study suggests that radiology teaching significantly improves student
      performance. Future work should look to define the contribution of "clinical
      exposure" towards this improvement, as well as the various teaching methods
      employed.

PMID- 15447966
TI  - Neurosarcoidosis: an unusual indication for radiotherapy.
AB  - Up to 70% of patients with systemic sarcoidosis developing neurosarcoidosis do so
      within the first 2 years of their systemic illness. Central nervous system (CNS)
      involvement as the only manifestation of sarcoidosis can be seen both at first
      time of disease and at recurrence in a few isolated cases. A young man showed
      neurological symptoms caused by isolated CNS sarcoidosis after unsuccessful
      treatment of primary pulmonary sarcoidosis by steroids. MRI scans of the head
      showed a distinct structural lesion temporodorsal in the left hemisphere and in
      the left-sided basal ganglia. The diagnosis was proved by neurosurgical
      resection. Post-operative systemic treatment with long-term corticosteroids was
      ineffective. After low-dose whole-brain irradiation of the isolated CNS lesion
      with 20 Gy, partial resolution of the clinical features and stabilization of
      disease proved by MRI ensued. In neurosarcoidosis the use of radiation therapy
      remains an appropriate therapy option with minimal adverse sequelae if primary
      medical treatment fails.

PMID- 15447967
TI  - Malignant mesothelioma of the tunica vaginalis testis.
AB  - Malignant mesothelioma of the tunica vaginalis is rare, and is usually not
      diagnosed until surgery is undertaken. Reports on the ultrasound features of this
      tumour are limited. We present an unusual case with ultrasound features mimicking
      an adenomatoid tumour.

PMID- 15447968
TI  - Renal angiomyolipoma with calcification: CT-pathology correlation.
AB  - Fat containing renal tumours are usually considered as angiomyolipomas on imaging
      modalities. Some cases of renal cell carcinoma have been reported. Although it
      has been previously reported, angiomyolipomas containing calcifications are very
      rare. We report a case of a fatty renal tumour with calcification which was an
      angiomyolipoma. The calcification within the tumour was secondary to osseous
      metaplasia.

PMID- 15447969
TI  - Isolated torsion of the hydrosalpinx: a rare presentation.
AB  - Isolated torsion of the Fallopian tube is a rare occurrence, which generally
      presents in the reproductive age group. It is difficult to diagnose on imaging
      and the diagnosis is established after laparoscopy. This report describes an
      unusual presentation of an uncommon condition in a perimenopausal 48-year-old
      woman who presented with lower abdominal discomfort. The clinical and imaging
      features led to a suspicion of ovarian neoplasm. Diagnostic laparoscopy revealed
      torsion of a left sided hydrosalpinx with benign serous cystadenoma of the left
      ovary. Torsion of the Fallopian tube is a rare event in the perimenopausal age
      group. It should however be included in the differential diagnosis of lower
      abdominal pain and recognition of imaging features may allow early surgical
      intervention.

PMID- 15447970
TI  - Cervical oesophageal stent placement via a retrograde transgastric route.
AB  - During attempted oesophageal stent placement in a patient with cervical
      oesophageal cancer in whom swallowing of even saliva was impossible, transoral
      access to the cervical oesophagus was unsuccessful. Under ultrasound and
      fluoroscopy guidance, percutaneous gastric puncture was performed, and using an
      angiographic catheter and guidewire, access to the oesophagus by a retrograde
      transgastric route was successfully achieved. The obstructed segment of the
      oesophagus was traversed. It was then possible to pull the guidewire through the
      mouth and place an oesophageal stent via an antegrade approach.

PMID- 15447971
TI  - A leaking breast prosthesis presenting as an abdominal mass.

PMID- 15447972
TI  - Pitfalls in the CT diagnosis of appendicitis.
AB  - CT evaluation of appendicitis represents an increasingly common emergency room
      request. While the overall accuracy of CT is high, numerous pitfalls exist which
      may deceive radiologists, resulting in a missed diagnosis of appendicitis. The
      inflamed appendix may be unusual in its location, or may appear normal if only a
      small portion of the distal appendix is involved (tip appendicitis). In a patient
      with a history of appendectomy, inflammation of the appendiceal stump may be
      easily missed. Appendicitis may closely mimic small bowel obstruction, or
      gynaecological disease, especially after perforation has occurred. Even a
      misleading clinical history may lead the radiologist's eye astray. This pictorial
      review demonstrates these and other potential radiological pitfalls, and includes
      important points for the accurate diagnosis of appendicitis.

PMID- 15447973
TI  - A patient with back pain and unusual appearances on bone scintigraphy.

PMID- 15447975
TI  - Baked beans on CT.

PMID- 15447976
TI  - L1CAM, INP10, P-cadherin, tPA and ITGB4 over-expression in malignant pleural
      mesotheliomas revealed by combined use of cDNA and tissue microarray.
AB  - Malignant pleural mesothelioma (MM) is a rare tumour with high mortality, which
      can exhibit various morphologies classified as epithelioid, biphasic and
      sarcomatoid subtypes. To investigate the molecular changes in these tumours, we
      studied gene expression patterns by combined use of cDNA arrays and tumour tissue
      microarrays (TMA). Deregulation of the expression of 588 cancer-related genes was
      screened in 16 MM comprising all three subtypes and compared with references,
      i.e. normal mesothelial cell lines and pleural mesothelium. Array data were
      analysed using three statistical methods; principal component analysis (PCA),
      permutation test and receiver operating characteristic (ROC) curves. Eleven genes
      were verified by real-time RT-PCR. Genes encoding two adhesion molecules [COL1A2
      and integrin beta4 (ITGB4)] and a chemokine (INP10) were up-regulated in MM
      compared with both the cell lines and pleural mesothelium. There was a type
      specific up-regulation of semaphorin E, ITGB4 and P-cadherin in epithelioid MM,
      matrix metalloproteinase 9 (MMP9) and tissue-type plasminogen activator (tPA) in
      sarcomatoid MM and neural cell adhesion molecule L1 (L1CAM) and INP10 in biphasic
      MM. Immunohistochemistry on TMA containing 47 MM (26 epithelioid, 15 sarcomatoid
      and six biphasic) was performed for five proteins, ITGB4, P-cadherin, tPA, INP10
      and L1CAM. INP10 expression was increased in MM in general compared with normal
      mesothelium, while increased expression of P-cadherin, L1CAM and ITGB4 was more
      specific in MMs exhibiting an epithelioid growth pattern. The over-expression of
      tPA was more frequent in epithelioid MM despite higher mRNA levels in sarcomatoid
      and biphasic MM. We conclude that several proteins, associated with cell adhesion
      either directly (ITGB4, L1CAM, P-cadherin) or as a regulatory factor (INP10), are
      differentially expressed in MM. In particular, INP10, ITGB4 and COL1A2 were up
      regulated in MM compared with both reference sample types, suggesting a
      relationship with development of these tumours.

PMID- 15447977
TI  - Activation of the RON receptor tyrosine kinase attenuates transforming growth
      factor-beta1-induced apoptotic death and promotes phenotypic changes in mouse
      intestinal epithelial cells.
AB  - The RON (recepteur d'origine nantais) receptor belongs to the MET proto-oncogene
      family that is implicated in the oncogenesis of the gastrointestinal epithelium.
      The present study aimed to determine the role of RON in regulating epithelial
      phenotypes in response to transforming growth factor (TGF)-beta1. Expression and
      activation of RON in SV40-immortalized mouse intestinal epithelial MODE-K cells
      result in reduction of cellular sensitivities towards apoptotic signals elicited
      by TGF-beta1. This effect is dependent on RON expression and phosphorylation that
      inhibit the TGF-beta1-induced activation of caspase-3 and truncation of BAD.
      Among cellular signaling components, the activation of MAP kinase is critical in
      the RON-mediated inhibitory effect. PD98059, a specific MAP kinase inhibitor,
      prevented RON-mediated anti-apoptotic activities. PD98059 also prevented the
      inhibitory effect of RON on TGF-beta1-induced cleavage of caspase-3 and BAD. By
      protecting cells from apoptotic death, activated RON collaborates with TGF-beta1
      in the induction of cell morphological changes with decreased E-cadherin
      expression and increased migration and morphogenesis. Thus, RON expression and
      activation modulate phenotypes of gastrointestinal epithelial cells in response
      to TGF-beta1 with reduced sensitivity to apoptosis and increased migration. These
      activities might represent a mechanism by which RON activation increases
      tumorigenic activities and facilitates the progression of transformed epithelial
      cells towards malignancy.

PMID- 15447978
TI  - Role of peroxisome proliferator-activated receptor-alpha (PPARalpha) in
      bezafibrate-induced hepatocarcinogenesis and cholestasis.
AB  - Prolonged administration of peroxisome proliferators to rodents typically leads
      to hepatocarcinogenesis. Peroxisome proliferator-activated receptor-alpha
      (PPARalpha) is required to mediate alterations in PPARalpha target gene
      expression, repress apoptosis, enhance replicative DNA synthesis, oxidative
      stress to DNA and hepatocarcinogenesis induced by the relatively specific
      PPARalpha agonist, Wy-14,643. Interestingly, administration of the less specific
      PPARalpha agonist, bezafibrate, leads to a modest induction of PPARalpha target
      genes in the absence of PPARalpha expression. In these studies, the role of
      PPARalpha in modulating hepatocarcinogenesis induced by long-term feeding of 0.5%
      bezafibrate was examined in wild-type (+/+) and PPARalpha-null (-/-) mice. The
      average liver weight was significantly higher in (+/+) and (-/-) mice fed
      bezafibrate than controls, but this effect was considerably less in (-/-) mice as
      compared with similarly treated (+/+) mice. Increased levels of mRNA encoding
      cell cycle regulatory proteins and DNA repair enzymes were found in (+/+) mice
      fed bezafibrate, and this effect was not found in (-/-) mice. In mice fed
      bezafibrate for 1 year, preneoplastic foci, adenomas and a hepatocellular
      carcinoma were found in (+/+) mice, while only a single microscopic adenoma was
      found in one (-/-) mouse. This effect was observed in both Sv/129 and C57BL/6N
      strains of mice, although only preneoplastic foci were observed in the latter
      strain. Interestingly, hepatic cholestasis was observed in 100% of the
      bezafibrate-fed (-/-) mice, and this was accompanied by significantly elevated
      hepatic expression of mRNA encoding bile salt export pump and lower expression of
      mRNA encoding cytochrome P450 7A1, consistent with enhanced activation of the
      bile acid receptor, farnesoid X receptor. Results from these studies demonstrate
      that the PPARalpha is required to mediate hepatocarcinogenesis induced by
      bezafibrate, and that PPARalpha protects against potential cholestasis.

PMID- 15447979
TI  - Is the gene expression pattern of lung cancer detected by screening with spiral
      computed tomography different from that of symptom-detected lung cancer?

PMID- 15447980
TI  - Truncating BRCA1 mutations are uncommon in a cohort of hereditary prostate cancer
      families with evidence of linkage to 17q markers.
AB  - PURPOSE: A genome-wide scan of 175 hereditary prostate cancer families from the
      University of Michigan Prostate Cancer Genetics Project provided evidence of
      prostate cancer linkage to 17q markers near the BRCA1 gene. To examine the
      possibility that germ-line BRCA1 mutations were associated with hereditary
      prostate cancer, individuals from 93 families with evidence of linkage to
      chromosome 17q were screened for germ-line BRCA1 mutations. EXPERIMENTAL DESIGN:
      One individual from each of the 93 families, the majority with three or more
      cases of prostate cancer, were screened for BRCA1 mutations with denaturing high
      performance liquid chromatography (HPLC). Fragments exhibiting denaturing HPLC
      variant patterns were additionally analyzed by direct sequencing. RESULTS: Sixty
      five of the individuals selected for sequencing from 65 unrelated families were
      determined to have wild-type BRCA1 sequence by denaturing HPLC. One individual
      from a family with both prostate and ovarian cancer was found to have a
      truncating BRCA1 mutation (3829delT). An additional 27 germ-line variants were
      identified, including 15 missense variants. CONCLUSIONS: These sequencing results
      suggest that BRCA1 truncating mutations do not account for the linkage evidence
      on chromosome 17 observed in University of Michigan Prostate Cancer Genetics
      Project families. A recently completed combined genome scan has also detected
      linkage to 17q22, and studies are ongoing to identify the relevant prostate
      cancer susceptibility gene in this region.

PMID- 15447981
TI  - Circulating nucleosomes predict the response to chemotherapy in patients with
      advanced non-small cell lung cancer.
AB  - PURPOSE: We investigated the potential of circulating, nucleosomal DNA for the
      early prediction of the efficacy of chemotherapy in patients with advanced lung
      cancer. EXPERIMENTAL DESIGN: In serum of 212 patients with newly diagnosed non
      small cell lung cancer (stages III and IV) undergoing chemotherapy, nucleosomes
      (ELISA, Roche) were measured at days 1, 3, 5, and 8 of the first cycle and before
      each new therapeutic cycle. Additionally, carcinoembryonic antigen and
      cytokeratin 19 fragments (CYFRA 21-1; Elecsys, Roche) were determined before each
      cycle. The therapeutic success was classified by computed tomography before start
      of the third cycle according to the World Health Organization criteria. RESULTS:
      In univariate analysis, responders (patients with remission) showed significantly
      (P < 0.05) lower values for the area under the curve of days 1 to 8 (AUC 1-8) of
      nucleosomes, the pretherapeutic baseline values of cycle 2 (BV2) and cycle 3
      (BV3) of nucleosomes, and higher decreases of the baseline values from cycle 1 to
      2 (BV1-2) and from cycle 1 to 3 (BV1-3) compared with nonresponders (patients
      with stable or progressive disease). Additionally, CYFRA 21-1 (BV1, BV2, BV3, BV1
      2, BV1-3) and carcinoembryonic antigen (BV1-2) discriminated significantly
      between both groups. In multivariate analysis including all parameters available
      until end of the first therapeutic cycle, nucleosomes (AUC 1-8), CYFRA 21-1
      (BV1), stage, and age were independent predictors of therapy response with
      nucleosomes (AUC 1-8) having the strongest impact. CONCLUSION: Circulating
      nucleosomes in combination with oncological biomarkers are valuable for the early
      estimation of the efficacy of chemotherapy in patients with lung cancer.

PMID- 15447982
TI  - Molecular cytogenetic identification of subgroups of grade III invasive ductal
      breast carcinomas with different clinical outcomes.
AB  - Tumor grade is an established indicator of breast cancer outcome, although
      considerable heterogeneity exists even within-grade. Around 25% of grade III
      invasive ductal breast carcinomas are associated with a "basal" phenotype, and
      these tumors are reported to be a distinct subgroup. We have investigated whether
      this group of breast cancers has a distinguishing pattern of genetic alterations
      and which of these may relate to the different clinical outcome of these
      patients. We performed comparative genomic hybridization (CGH) analysis on 43
      grade III invasive ductal breast carcinomas positive for basal cytokeratin 14, as
      well as 43 grade- and age-matched CK14-negative controls, all with up to 25 years
      (median, 7 years) of clinical follow-up. Significant differences in CGH
      alterations were seen between the two groups in terms of mean number of changes
      (CK14+ve - 6.5, CK14-ve - 10.3; P = 0.0012) and types of alterations at
      chromosomes 4q, 7q, 8q, 9p, 13q, 16p, 17p, 17q, 19p, 19q, 20p, 20q and Xp.
      Supervised and unsupervised algorithms separated the two groups on CGH data alone
      with 76% and 74% accuracy, respectively. Hierarchical clustering revealed
      distinct subgroups, one of which contained 18 (42%) of the CK14+ve tumors. This
      subgroup had significantly shorter overall survival (P=0.0414) than other grade
      III tumors, regardless of CK14 status, and was an independent prognostic marker
      (P=0.031). These data provide evidence that the "basal" phenotype on its own does
      not convey a poor prognosis. Basal tumors are also heterogeneous with only a
      subset, identifiable by pattern of genetic alterations, exhibiting a shorter
      overall survival. Robust characterization of this basal group is necessary if it
      is to have a major impact on management of patients with breast cancer.

PMID- 15447983
TI  - Hypermethylation in histologically distinct classes of breast cancer.
AB  - PURPOSE: A number of different genes are known to be inactivated by aberrant
      hypermethylation in breast cancer, but it is still unknown to what extent these
      epigenetic alterations differ according to specific breast cancer phenotypes. We
      sought to determine whether the extent of hypermethylation or defined profiles of
      gene hypermethylation are associated with biological characteristics of breast
      cancers. EXPERIMENTAL DESIGN: We evaluated methylation status of 12 different
      genes in a series of 109 invasive breast tumors, representing the ductal,
      lobular, and mucinous histologic subtypes using methylation-specific PCR.
      Frequencies of methylation were compared across the recognized histologic
      classes, and multivariate techniques (latent class analysis, factor analysis,
      recursive partitioning, and hierarchical clustering) were used to seek patterns
      of methylation for individual genes that distinguish recognized histologic types
      of breast cancer or define breast cancer phenotypes on a molecular level.
      RESULTS: All 109 cases studied have aberrant methylation of multiple genes (3 to
      10 genes per case), demonstrating that gene hypermethylation is pervasive in
      breast cancer. Lobular cancers and mucinous cancers, which often have relatively
      low levels of chromosomal changes, have higher overall frequencies of
      hypermethylation than ductal cancers (49% in lobular and mucinous versus 40% in
      ductal), but there is a relatively unimodal distribution of methylation frequency
      for all three histologic types. Only one of the individual genes studied, BRCA1,
      has a variable frequency of methylation that is significantly dependent on
      histologic pattern of tumor growth, with a higher frequency of methylation in
      mucinous cancers than ductal or lobular cancers. Although some trends of
      histology-specific gene methylation were seen, methylation patterns could not
      definitively classify breast cancers according to histologic type. CONCLUSIONS:
      Although a more comprehensive hypermethylation profile could potentially be
      useful for breast cancer classification and understanding the biology of this
      disease, it appears that the hypermethylation patterns across various forms of
      breast cancer are less distinct than those between breast cancer and cancers of
      different tissue origins. Furthermore, the relatively unimodal distribution of
      methylation frequency for all three histologic types does not support there being
      a distinct CpG island methylator phenotype for breast cancer.

PMID- 15447984
TI  - Effects of gefitinib on serum epidermal growth factor receptor and HER2 in
      patients with advanced non-small cell lung cancer.
AB  - PURPOSE: The aim of this study was to assess serum extracellular binding domains
      of epidermal growth factor receptor (EGFR) and HER2 as surrogate markers of
      Gefitinib (Iressa, ZD1839, AstraZeneca, London, United Kingdom) activity in
      patients with non-small cell lung cancer. EXPERIMENTAL DESIGN: Serum EGFR and
      HER2 levels were monitored in blood samples taken within 1 week of starting
      Gefitinib at day 28 and at every computed tomography scan evaluation. EGFR and
      HER-2 were assayed in duplicate using commercial sandwich enzyme-linked
      immunosorbent assay kits (Oncogene Science Bayer Corporation, Cambridge, UK). A
      logistic regression analysis was performed to evaluate: (1) the relationship
      between best overall tumor response and basal EGFR and HER2 levels, and (2) the
      association between best overall tumor response and the differences of EGFR and
      HER2 levels obtained at the best overall tumor response and at baseline. RESULTS:
      Forty-six pretreated patients were evaluated, including F/M:11/35, Eastern
      Cooperative Oncology Group performance status 0-1/2:39/7, IIIB/IV:11/35, and
      adenocarcinoma/nonadenocarcinoma 29/17. Five partial responses (11%) and 14
      stable disease responses (30%) were observed. Median pretreatment EGFR and HER2
      were 83.3 ng/ml and 13.7 ng/ml. For baseline EGFR and HER2, the odds ratio of
      progression was 0.95 [95% confidence interval (CI), 0.91-0.98; P=0.01] and 0.87
      (95% CI, 0.74-1.03; P=0.11), respectively. The difference between the best
      overall tumor response and basal EGFR value was predictive for response with a 6%
      increase in the odds of progression for an increase of 1 ng/ml (odds ratio, 1.06;
      95% CI, 1.01-1.11; P=0.009) and for progression-free survival with a hazard ratio
      of 1.03 (95% CI, 1.01-1.04; P=0.003). CONCLUSION: Modifications of EGFR serum
      values during treatment seem to reflect Gefitinib activity.

PMID- 15447985
TI  - Comprehensive characterization of annexin I alterations in esophageal squamous
      cell carcinoma.
AB  - PURPOSE: The purpose is to characterize alterations of the annexin I gene, its
      mRNA, and protein expression in esophageal squamous cell carcinoma. EXPERIMENTAL
      DESIGN: Fifty-six cases of esophageal squamous cell carcinoma were analyzed using
      four microsatellite markers flanking the annexin I gene (9q11-q21) to identify
      loss of heterozygosity. In addition, we performed (a) single-strand conformation
      polymorphism and DNA sequencing along the entire promoter sequence and coding
      region to identify mutations, (b) real-time quantitative reverse transcription
      PCR of RNA from frozen esophageal squamous cell carcinoma tissue (n = 37) and in
      situ hybridization (n = 5) on selected cases to assess mRNA expression, and (c)
      immunohistochemistry (n = 44) to evaluate protein expression. The prevalence of
      the allelic variants identified in the first 56 patients was refined in 80
      additional esophageal squamous cell carcinoma patients and 232 healthy
      individuals. RESULTS: Forty-six of 56 (82%) esophageal squamous cell carcinoma
      patients showed loss of an allele at one or more of the four microsatellite
      markers; however, only one (silent) mutation was seen. Two intragenic variants
      were identified with high frequency of allelic loss (A58G, 64%; L109L, 69%).
      Thirty of 37 (81%) esophageal squamous cell carcinoma patients showed reduced
      annexin I mRNA expression, which was confirmed by in situ hybridization, whereas
      annexin I protein expression was reduced in 79% of poorly differentiated tumor
      cell foci but in only 5% of well-differentiated tumor foci, although allelic loss
      on chromosome 9 was found in both tumor grades. CONCLUSIONS: Allelic loss of
      annexin I occurs frequently, whereas somatic mutations are rare, suggesting that
      annexin I is not inactivated in esophageal squamous cell carcinoma via a two-hit
      mechanism. A decrease in annexin I protein expression was confirmed, consistent
      with a quantitative decrease in mRNA expression, and appeared to be related to
      tumor cell differentiation. We conclude that annexin I is not the tumor
      suppressor gene corresponding to the high levels of loss of heterozygosity
      observed on chromosome 9 in esophageal squamous cell carcinoma; however,
      dysregulation of mRNA and protein levels is associated with this tumor type.

PMID- 15447986
TI  - Lung cancers detected by screening with spiral computed tomography have a
      malignant phenotype when analyzed by cDNA microarray.
AB  - PURPOSE: Spiral computed tomography (CT) can detect lung cancer at an early
      stage, but the malignant potential is unknown. The question is, as follows: do
      these small lesions have the same lethal potential as do symptomatic tumors?
      EXPERIMENTAL DESIGN: We used a cDNA microarray platform and compared the gene
      expression profile of spiral CT-detected lung carcinomas with a matched case
      control population of patients presenting with symptomatic lung cancer. RESULTS:
      CT-detected and symptomatic tumors have shown a comparable gene expression
      profile. Correspondence analysis has demonstrated that nine genes were
      differentially expressed, although with a high variability across the samples
      that prevented distinguishing the two groups of tumors. Analysis of these nine
      genes has suggested that early-detected tumors have higher levels of retinoic
      acid production and higher expression levels of caveolin 2, matrix Gla, and
      cystatin A, which are already known to be lost during tumor progression.
      CONCLUSIONS: All of the tumors observed are histologically malignant according to
      the WHO Classification. Early lung cancers that are detected by screening have a
      gene expression pattern similar to, but not identical to, that of symptomatic
      lung carcinomas.

PMID- 15447987
TI  - Molecular prediction of response to 5-fluorouracil and interferon-alpha
      combination chemotherapy in advanced hepatocellular carcinoma.
AB  - PURPOSE: The prognosis of hepatocellular carcinoma (HCC) is very poor,
      particularly in patients with tumors that have invaded the major branches of the
      portal vein. Combination chemotherapy with intra-arterial 5-fluorouracil and
      subcutaneous interferon-alpha has shown promising results for such advanced HCC,
      but it is important to develop the ability to accurately predict chemotherapeutic
      responses. EXPERIMENTAL DESIGN: We analyzed the expression of 3,080 genes using a
      polymerase chain reaction-based array in 20 HCC patients who were treated with
      combination chemotherapy after reduction surgery. After unsupervised analyses, a
      supervised classification method for predicting chemotherapeutic responses was
      constructed. To minimize the number of predictive genes, we used a random
      permutation test to select only significant (P < 0.01) genes. A leave-one-out
      cross-validation confirmed the gene selection. We also prepared an additional 11
      cases for validation of predictive performance. RESULTS: Hierarchical clustering
      analysis and principal component analysis with all 3,080 genes revealed distinct
      gene expression patterns in responders (those with complete response or partial
      response) and nonresponders (those with stable disease or progressive disease) to
      the combination chemotherapy. Using a weighted-voting classification method with
      either all genes or only significant genes as assessed by permutation testing,
      the objective responses to treatment were correctly predicted in 17 of 20 cases
      (accuracy, 85%; positive predictive value, 100%; negative predictive value, 80%).
      Moreover, patients in the validation dataset could be classified into two
      distinct prognostic groups using 63 predictive genes. CONCLUSIONS: Molecular
      analysis of 63 genes can predict the response of patients with advanced HCC and
      major portal vein tumor thrombi to combination chemotherapy with 5-fluorouracil
      and interferon-alpha.

PMID- 15447988
TI  - Mammaglobin expression in leukapheresis products is a predictive marker of poor
      prognosis in women with high-risk breast cancer.
AB  - PURPOSE: The purpose of this study was to investigate the incidence and
      prognostic relevance of tumor cell detection in granulocyte colony-stimulating
      factor-mobilized peripheral blood progenitor cell collections (PBPCCs) using
      cytokeratin (CK), maspin (MAS), and mammaglobin (MAM) genes as epithelial cell
      markers. The population on which the study was conducted was drawn from stage III
      breast cancer patients undergoing high-dose chemotherapy and autologous
      transplantation with PBPCCs. EXPERIMENTAL DESIGN: One hundred and ninety-four
      patients were enrolled in the study and analyzed for tumor cell detection on the
      basis of 481 PBPCCs gathered before administration of chemotherapy. CK, MAS, and
      MAM gene expressions were investigated by means of the reverse transcription
      nested polymerase chain reaction, and those samples expressing CK were further
      hybridized with a radiolabeled internal probe to reduce false-positive results.
      Sensitivity and specificity were assessed on 37 controls (12 cell lines, 12
      healthy donors, and 13 nonepithelial malignancies). Each of the known prognostic
      variables (age, stage, lymph node status, receptor status, c-ErbB2 status, and
      Ki67 status) was then analyzed (both individually and together with CK, MAS, and
      MAM expression on PBPCCs) in relation to patient overall survival (OS) and
      relapse-free survival (RFS). RESULTS: After a 3-year follow-up, an estimated 83%
      (95% confidence interval, 77.1-88.8%) of the patients were alive and an estimated
      67% (95% confidence interval, 60.1-74.6%) were free of relapse. One hundred and
      seventy-six of the 194 patients (91%) had contaminated PBPCCs evidenced by at
      least one positive sample for any of the markers evaluated. The PBPCC frequency
      of CK, MAS, and MAM positivity (+) was 71%, 36%, and 16%, respectively. MAM
      expression on PBPCC was associated with an increased risk of relapse (P = 0.003),
      whereas CK and MAS expressions were not associated with changes in either RFS or
      OS. CONCLUSIONS: MAM gene expression on leukapheresis products of high-risk
      breast cancer patients is an indicator of poor prognosis. The method of
      evaluation is simple and reproducible and provides new tools for evaluating the
      role played by tumor cells in apheresis products and their potential in causing
      metastasis.

PMID- 15447989
TI  - Identification of a novel human cancer/testis antigen, KM-HN-1, recognized by
      cellular and humoral immune responses.
AB  - PURPOSE: We used serologic screening of a cDNA expression library of human testis
      to identify novel cancer/testis antigens that elicit both humoral and cellular
      immune responses in cancer patients. EXPERIMENTAL DESIGN AND RESULTS: We
      identified a novel gene designated KM-HN-1 the expression of which is testis
      specific among normal tissues; it contains coiled coil domains and a leucine
      zipper motif and encodes a putative protein consisting of 833 amino acids. KM-HN
      1 expression was observed in various cancer tissues and cancer cell lines at both
      mRNA and protein levels. Immunofluorescence staining of an esophageal cancer cell
      line revealed that KM-HN-1 protein was present exclusively in the nucleus during
      mitosis. Recombinant KM-HN-1 protein was produced, and used for ELISA to
      quantitate levels of IgG antibody specific to KM-HN-1. Higher levels of IgG
      antibodies specific to KM-HN-1 were detected in many types and numbers of cancer
      patients but not in healthy donors. The CTL lines specific to KM-HN-1, generated
      from HLA-A*2402-positive healthy donors and cancer patients, killed human
      leukocyte antigen (HLA)-A24-positive cancer cells expressing KM-HN-1 but not cell
      lines that did not express either KM-HN-1 or HLA-A24. CONCLUSIONS: We identified
      a novel cancer/testis antigen, KM-HN-1, which elicited humoral immune responses
      in patients with various types of cancer. Furthermore, KM-HN-1-specific CTLs
      could be generated from both healthy donors and cancer patients, which indicated
      that KM-HN-1 can be a candidate for an ideal target for cancer immunotherapy.

PMID- 15447990
TI  - Low-dose suramin enhanced paclitaxel activity in chemotherapy-naive and
      paclitaxel-pretreated human breast xenograft tumors.
AB  - We reported induction of broad-spectrum chemoresistance by acidic and basic
      fibroblast growth factors and chemosensitization by their nonspecific inhibitor
      suramin at nontoxic and subtherapeutic doses. This study evaluated whether low
      dose suramin enhances paclitaxel activity in chemotherapy-naive and paclitaxel
      pretreated human MCF7 breast xenograft tumors in mice. Suramin, 10 mg/kg, and/or
      paclitaxel, 15 mg/kg, were administered intravenously, twice weekly for 2 to 3
      weeks. In addition to conventional end points [tumor size change, median survival
      time (MST)], we also used clinically relevant end points [partial (PR) and
      complete response rates (CR); progressive disease (PD); stable disease (SD); time
      to tumor progression (TTP)]. In chemotherapy-naive mice, the control and suramin
      groups showed identical TTP (3 days) and MST (21 days). Single-agent paclitaxel
      produced 47% PR and 24% CR, and prolonged both TTP and MST to 73 days. The
      addition of suramin further improved the total response rate to 100% with a
      dramatically greater 63% CR, shortened the time to attain PR and CR, and
      prolonged TTP and MST to > or =136 days. In the paclitaxel-pretreated group,
      single-agent paclitaxel resulted in 67% SD and 33% PD, whereas the combination
      produced 50% PR and 50% SD. Suramin also significantly enhanced the apoptotic
      effect of paclitaxel in tumors. In conclusion, suramin improved the activity of
      paclitaxel in both chemotherapy-naive and paclitaxel-pretreated animals, without
      enhancing host toxicity (< or =10% body weight loss in all groups). These data
      have led to the initiation of phase I/II trials of paclitaxel and low-dose
      suramin combination in advanced metastatic breast cancer patients.

PMID- 15447991
TI  - Enhancement of xenograft tumor radiosensitivity by the histone deacetylase
      inhibitor MS-275 and correlation with histone hyperacetylation.
AB  - PURPOSE: Histone deacetylase (HDAC) inhibitors are undergoing clinical evaluation
      in cancer therapy. Because HDAC modulation has been shown to enhance the
      radiosensitivity of tumor cells in vitro, we investigated the effects of the HDAC
      inhibitor MS-275 on the radioresponse of DU145 prostate carcinoma xenografts.
      EXPERIMENTAL DESIGN: As an indicator of HDAC inhibition in vivo, the histone
      acetylation status in tumor lysates was determined after two, four, and six
      injections of MS-275 delivered at 12-hour intervals, as well as 24 and 48 hours
      after the last injection. Tumor growth delay studies were then performed using
      this DU-145 xenograft model with radiation administered to leg tumors after the
      fourth dose of MS-275, which corresponded to the time of maximum histone
      hyperacetylation. RESULTS: An increase in histone hyperacetylation was detected
      in each tumor after two injections of MS-275 with a maximum hyperacetylation
      occurring after four to six injections. In tumor growth delay studies, the
      combination of MS-275 and radiation resulted in a greater than additive
      inhibition of tumor growth as compared with the individual modalities. As
      alternative sources for an indicator of drug radiosensitizing activity, histone
      hyperacetylation was determined in a series of normal tissues, including
      lymphocytes. Each of the normal tissues also had a maximal histone
      hyperacetylation after four to six injections of MS-275. CONCLUSIONS: These
      studies show that MS-275 enhances the radiosensitivity of DU145 xenografts and
      suggest that histone hyperacetylation status can serve as a useful marker for
      drug radiosensitizing activity.

PMID- 15447992
TI  - Cyclophosphamide dose intensification during induction therapy for intermediate
      risk pediatric rhabdomyosarcoma is feasible but does not improve outcome: a
      report from the soft tissue sarcoma committee of the children's oncology group.
AB  - PURPOSE: More than half of pediatric rhabdomyosarcoma cases have intermediate
      risk features and suboptimal outcome (3-year failure-free survival estimates, 55
      to 76%). Dose intensification of known active agents may improve outcome.
      EXPERIMENTAL DESIGN: This pilot study evaluated the feasibility of dose
      intensification of cyclophosphamide in previously untreated patients ages < 21
      years with intermediate-risk rhabdomyosarcoma. Induction therapy comprised four 3
      week cycles of VAC: vincristine (V) 1.5 mg/m2 on days 0, 7, and 14; actinomycin D
      (A) 1.35 mg/m2 on day 0; and dose-intensified cyclophosphamide (C) on days 0, 1,
      and 2. The three cyclophosphamide dose levels tested were as follows: (a) 1.2
      g/m2/dose; (b) 1.5 g/m2/dose; and (c) 1.8 g/m2/dose. Continuation therapy
      comprised nine additional cycles of VAC with 2.2 g/m2/cycle of C. Radiotherapy
      was administered at week 0 (parameningeal tumors with intracranial extension) or
      week 12 or 15 (all others). RESULTS: Between October 1996 and August 1999, 115
      eligible patients were enrolled. Three of 15 patients treated at dose level 2
      experienced life-threatening dose-limiting toxicity (typhlitis +/- other severe
      toxicity). Dose level 1 was the maximum-tolerated dose, and 91 evaluable patients
      were treated at this level. The 3-year failure-free and overall survival
      estimates for patients treated at the maximum-tolerated dose were 52% (95%
      confidence interval, 41-64%) and 67% (95% confidence interval, 56-77%),
      respectively, at a median follow-up of 3 years. CONCLUSIONS: A 64% increase in
      the standard cyclophosphamide dosage during induction (to 3.6 g/m2/cycle) was
      tolerated. However, outcomes were similar to those observed at lower dosages,
      suggesting that alkylator dose intensification does not benefit patients with
      intermediate-risk rhabdomyosarcoma.

PMID- 15447993
TI  - Sequential intraperitoneal topotecan and oral etoposide chemotherapy in recurrent
      platinum-resistant ovarian carcinoma: results of a phase II trial.
AB  - PURPOSE: The purpose is to investigate the safety and efficacy of i.p. topotecan
      and oral etoposide as salvage treatment for patients with platinum-resistant
      ovarian or primary peritoneal cancer. EXPERIMENTAL DESIGN: Patients were treated
      with i.p. topotecan initial dose, 1 mg/m2 on days 1 to 5, followed by oral
      etoposide 100 mg on days 6 to 9 of a 28-day cycle for six cycles. Dose reduction
      of topotecan was used for severe bone marrow suppression. Peritoneal (topotecan)
      and plasma (topotecan and etoposide) levels were assessed at multiple time points
      using high-pressure liquid chromatography. RESULTS: Twenty-two patients (mean
      age, 61 years) with a median of 1.5 prior treatments were enrolled. Etoposide
      peak plasma concentrations ranged from 1.9 to 6.9 microg/mL (mean, 3.6
      microg/mL). Topotecan plasma levels rose with increasing peritoneal concentration
      and were detectable within 1 hour but tended to decrease rapidly to below
      detectable levels within 24 hours. The peak plasma concentration of topotecan was
      12.82 +/- 8.55 microg/mL with a plasma half-life of 6.17 +/- 2.75 hours. A total
      of 104 cycles was administered; 14 patients (64%) completed all six planned
      cycles. All patients were evaluable for toxicity, and 21 patients were evaluable
      for response. The most common grade 4 toxicities were neutropenia and
      thrombocytopenia in eight and four patients (36 and 18%), respectively. There
      were no treatment-related deaths. The overall response rate was 38% [complete
      response, three (14%); partial response, five (24%)]. Seven patients had stable
      disease and six progressed while on treatment. CONCLUSIONS: The combination of
      i.p. topotecan and oral etoposide is an active and well-tolerated regimen in
      platinum-resistant ovarian carcinoma. Additional studies investigating topotecan
      in combination with etoposide are warranted.

PMID- 15447994
TI  - A phase I/II study of LY900003, an antisense inhibitor of protein kinase C-alpha,
      in combination with cisplatin and gemcitabine in patients with advanced non-small
      cell lung cancer.
AB  - PURPOSE: Protein kinase C-alpha has been implicated in malignant transformation
      and proliferation. Based on in vivo superadditive interaction between the protein
      kinase C-alpha antisense oligonucleotide LY900003 (Affinitak, ISIS 3521) and
      cisplatin, we designed this phase I/II trial of LY900003 with
      cisplatin/gemcitabine. EXPERIMENTAL DESIGN: The safety of the combination, as
      well as potential pharmacokinetic interactions, was evaluated in the phase I
      portion of the trial. The phase II portion evaluated the antitumor activity of
      the combination in previously untreated patients with stage IIIB/IV non-small
      cell lung cancer (NSCLC). RESULTS: Seven patients received 18 cycles of the
      combination during the phase I portion. Dose-limiting toxicity was only observed
      in one of six evaluable patients (grade 3 fatigue). However, due to a relatively
      high frequency of thrombocytopenia, cisplatin 80 (mg/m2) and gemcitabine (1,000
      mg/m2) were recommended for the phase II portion. Antitumor activity was observed
      in two patients (one with NSCLC and one with pancreatic carcinoma), and prolonged
      stabilization was observed in two others. No pharmacokinetic interactions
      occurred. In the phase II portion, 55 NSCLC patients received the combination at
      two gemcitabine doses [1,000 mg/m2, n=44 (original cohort); 1,250 mg/m2, n=11
      (expanded cohort)]. Fourteen of 39 evaluable patients in the original cohort had
      a response rate (1 complete response and 13 partial responses; response, 36%),
      whereas 2 of 9 evaluable patients in the expanded cohort experienced partial
      response (combined response rate, 33%). The median time to treatment failure was
      3.9 months, whereas the median time response to progression for the 48 patients
      with evaluable response was 4.4 months (confidence interval, 3.5-5.5 months).
      Intent to treat median survival time was 8.9 months. Forty-eight percent of the
      patients experienced catheter-related events. CONCLUSIONS: LY900003 can be
      administered safely in combination with cisplatin and gemcitabine and is
      associated with antitumor activity in patients with advanced NSCLC. Better
      characterization of subsets of patients most likely to benefit from this
      combination therapy is needed.

PMID- 15447995
TI  - Vaccination of patients with small-cell lung cancer with synthetic fucosyl GM-1
      conjugated to keyhole limpet hemocyanin.
AB  - PURPOSE: Immunotherapy directed toward cell surface antigens may provide a novel
      approach to the eradication of chemoresistant micrometastatic disease in patients
      with small-cell lung cancer (SCLC). Studies in SCLC cell lines and human tissues
      suggest that the ganglioside fucosyl GM1 is an abundant yet specific target. A
      prior clinical study demonstrated the potent immunogenicity of fucosyl GM-1
      derived from bovine thyroid gland, conjugated to keyhole limpet hemocyanin (KLH)
      and administered with QS-21 adjuvant. EXPERIMENTAL DESIGN: We tested the
      immunogenicity of three different doses of a synthetic version of fucosyl-GM1 in
      patients with SCLC after a major response to initial therapy. The primary end
      point was to establish the lowest effective dose capable of inducing antibody
      production. RESULTS: Five of six patients at the 30-microg dose and three of five
      patients at the 10-microg dose mounted IgM responses of 1:80 or greater. These
      antibodies were confirmed by flow cytometry in seven of eight cases. None of the
      patients at the 3-microg dose had titers above 1:80. One patient at the 30-microg
      dose had an IgG response with a titer of 1:80. The sera from six of the eight
      responders induced potent complement-mediated cytotoxicity of tumor cells.
      CONCLUSIONS: Vaccination with the synthetic fucosyl GM1-KLH conjugate induces an
      IgM antibody response against fucosyl GM1 and tumor cells expressing fucosyl GM1,
      comparable with the response induced by the bovine derivative. We plan to combine
      synthetic fucosyl GM1 vaccine at a dose of 30 microg with vaccines against three
      other antigens-GM2, Globo H, and polysialic acid-to test in patients with SCLC
      after initial chemotherapy.

PMID- 15447996
TI  - Combination immunotherapy of B-cell non-Hodgkin's lymphoma with rituximab and
      interleukin-2: a preclinical and phase I study.
AB  - PURPOSE: Cytokine-induced modulation of innate immunity is being explored to
      enhance the activity of monoclonal antibodies. Severe combined immunodeficient
      (SCID) mice engrafted with peripheral blood leukocytes (PBLs) from Epstein Barr
      virus-seropositive donors develop human B-cell non-Hodgkin's lymphomas [B-NHLs
      (hu-PBL-SCID mouse model)]. We used this hu-PBL-SCID mouse model to study the
      synergism between interleukin (IL)-2 and rituximab. We also conducted a phase I
      trial of IL-2 and rituximab in relapsed B-NHL to study whether expansion of
      natural killer (NK) cells and enhanced cellular cytotoxicity could be safely
      accomplished in vivo. EXPERIMENTAL DESIGN: Hu-PBL-SCID mice were treated with
      various schedules of rituximab and IL-2, with survival as the end point. Patients
      with relapsed B-NHL received rituximab (375 mg/m2 weekly x 4) followed by daily
      low-dose IL-2 (1 MIU/m2/day x 4 weeks) with pulses of intermediate-dose IL-2 (3
      15 MIU/m2). Toxicity, NK cell numbers, and cellular cytotoxicity were measured.
      RESULTS: In the hu-PBL-SCID mouse, the combination of rituximab and IL-2 showed
      greater activity against B-NHL than either agent alone. Treatment was most
      effective when IL-2 was given before rituximab. Twelve patients with heavily
      pretreated B-NHL entered the phase I trial. Toxicity was manageable, and
      responses were observed. NK cell expansion and enhanced cellular cytotoxicity
      against a B-cell lymphoma target were observed but did not correlate with
      response. CONCLUSIONS: The combination of IL-2 and rituximab is synergistic
      against B-NHL in the hu-PBL-SCID model. In the phase I trial, a sequential
      combination of rituximab and IL-2 was well tolerated and achieved biological end
      points. Responses were observed.

PMID- 15447997
TI  - Phase II study of the proteasome inhibitor bortezomib (PS-341) in patients with
      metastatic neuroendocrine tumors.
AB  - PURPOSE: This phase II study was undertaken to assess objective response,
      toxicity, tumor marker response, and pharmacodynamics of bortezomib in patients
      with metastatic neuroendocrine (carcinoid and islet cell) tumors. EXPERIMENTAL
      DESIGN: A total of 16 patients with measurable metastatic carcinoid (n=12) or
      islet cell (n=4) tumors received i.v. bolus of single agent bortezomib at a dose
      of 1.5 mg/m2 on days 1, 4, 8, and 11 every 21 days. Tumor response was assessed
      at 12-week intervals using Response Evaluation Criteria in Solid Tumors (RECIST)
      criteria. All patients were chemotherapy naive and had Eastern Cooperative
      Oncology Group performance status of 0 to 1. RESULTS: No patient achieved a
      partial or a complete remission. The patients received total of 264 doses of
      therapy with a median of 15 doses per patient. Grade 4 toxicities were not
      observed. The most common grade 3 adverse events included peripheral sensory
      neuropathy (37%), diarrhea (25%), vomiting (18%), and ileus (18%). Six of 10
      patients who experienced grade 2 to 3 peripheral sensory neuropathy also had
      grade 2 to 3 dizziness (n=2), orthostatic hypotension (n=2), syncope (n=1), ileus
      (n=2), or abdominal cramps (n=1). Changes in tumor marker levels did not
      correlate with tumor response. The mean percentage of 20S proteasome inhibition
      achieved in whole blood at 1 and 24 hours after bortezomib administration was 68
      and 30%, respectively. CONCLUSIONS: Despite achieving the surrogate biologic end
      point, single-agent bortezomib did not induce any objective responses in patients
      with metastatic carcinoid or islet cell tumors. Additional investigation is
      warranted to clarify the possible association of autonomic neuropathy with
      bortezomib.

PMID- 15447998
TI  - Value of p16INK4a and RASSF1A promoter hypermethylation in prognosis of patients
      with resectable non-small cell lung cancer.
AB  - The p16INK4a and RASSF1A are tumor suppressor genes frequently inactivated by de
      novo promoter hypermethylation in non-small cell lung cancer. We studied 119
      patients with non-small cell lung cancer (70 stage I/II and 49 stage IIIA) who
      had undergone surgery with curative intent. The p16INK4a and RASSF1A promoter
      methylation statuses were determined by methylation-specific PCR. Statistical
      analyses, all two-sided, were performed to determine the prognostic effect of
      hypermethylation on various clinical parameters. Hypermethylation of the p16INK4a
      and RASSF1A promoters was found in 58 (49%) and 46 (39%) tumors, respectively,
      and 30 tumors (25%) exhibited hypermethylation of both gene promoters. In
      patients with stage I/II tumors, only p16INK4a promoter hypermethylation was
      associated with a poor 5-year overall survival rate (P=0.002). In patients with
      stage IIIA disease, however, RASSF1A promoter hypermethylation was a stronger
      predictor of a poor 5-year overall survival rate (P < 0.0001) than p16INK4a
      promoter hypermethylation. Among the 49 patients with stage IIIA tumors, 16 (89%)
      of the 18 patients whose tumors showed RASSF1A promoter hypermethylation died
      within 3 years after surgery, as compared with only 12 (39%) of the 31 patients
      whose tumors had no RASSF1A promoter hypermethylation (P < 0.0001). Multivariate
      analysis indicated that RASSF1A promoter hypermethylation was the stronger
      independent predictor for survival in patients with locally advanced non-small
      cell lung cancer. Our results indicate that p16INK4a promoter hypermethylation
      predicts a poor 5-year survival rates for patients with resectable non-small cell
      lung cancer, particularly for those with early stage tumors, whereas RASSF1A
      promoter hypermethylation is a profound prognostic predictor for patients with
      locally advanced non-small cell lung cancer, suggesting an important role of
      RASSF1A in non-small cell lung cancer progression.

PMID- 15447999
TI  - Aberrant promoter hypermethylation of multiple genes in gallbladder carcinoma and
      chronic cholecystitis.
AB  - PURPOSE: Aberrant methylation of 5' gene promoter regions is an epigenetic
      phenomenon that is a major mechanism for silencing of tumor suppressor genes in
      many cancer types. There is limited information about the molecular changes
      involved in the pathogenesis of gallbladder carcinoma (GBC), including
      methylation status. EXPERIMENTAL DESIGN: We investigated the aberrant promoter
      methylation profile of 24 known or suspected tumor suppressor genes in 50 GBCs
      and compared those results with the findings in 25 chronic cholecystitis (CC)
      specimens without cancer. The methylation-specific polymerase chain reaction and
      combined restriction analysis methods were used to detect methylation, and the
      results were confirmed by sequencing of cloned polymerase chain reaction
      products. RESULTS: In GBC, gene methylation frequencies varied from 0% to 80%.
      Ten genes demonstrated relatively high frequencies of aberrant methylation: SHP1
      (80%), 3-OST-2 (72%), CDH13 (44%), P15INK4B (44%), CDH1 (38%), RUNX3 (32%), APC
      (30%), RIZ1 (26%), P16INK4A (24%), and HPP1 (20%). Eight genes (P73, RARbeta2,
      SOCS-1, DAPK, DcR2, DcR1, HIN1, and CHFR) showed low frequencies (2-14%) of
      methylation, and no methylation of the remaining six genes (TIMP-3, P57, RASSF1A,
      CRBP1, SYK, and NORE1) was detected. In CC, methylation was detected for seven
      genes: SHP1 (88%), P15INK4B (28%), 3-OST-2 (12%), CDH1 (12%), CDH13 (8%), DcR2
      (4%), and P16INK4A (4%). Significantly higher frequencies of methylation in GBC
      compared with CC were detected for eight genes (3-OST-2, CDH13, CDH1, RUNX3, APC,
      RIZ1, P16INK4A, and HPP1). Of those, four genes showed frequent methylation
      (>30%) in GBCs. The mean methylation index, an expression of the amount of
      methylated genes by case, was significantly higher in GBC (0.196 +/- 0.013)
      compared with CC (0.065 +/- 0.008; P < 0.001). CONCLUSIONS: Our study constitutes
      the most comprehensive methylation profile report available in GBC and
      demonstrates that this neoplasm has a distinct pattern of abnormal gene
      methylation. Whereas gallbladders from healthy individual were not available, our
      finding of methylation in CC cases without cancer suggests that this phenomenon
      represents an early event in the pathogenesis of GBC.

PMID- 15448000
TI  - Overexpression of the nuclear receptor coactivator AIB1 (SRC-3) during
      progression of pancreatic adenocarcinoma.
AB  - PURPOSE: The nuclear receptor coactivator amplified in breast cancer 1 (AIB1) was
      found to be amplified and overexpressed in breast and some other epithelial
      tumors. We have reported that expression of AIB1 is rate limiting for growth
      factor, as well as hormone signaling. Here, we assess the involvement of AIB1 in
      the development of pancreatic adenocarcinoma. EXPERIMENTAL DESIGN: We
      investigated expression levels of AIB1 protein and mRNA in pancreatic cancer cell
      lines and in a series of archival pancreatic adenocarcinoma (n=78), pancreatic
      intraepithelial neoplasia (n=93), pancreatitis (n=28), and normal pancreas
      tissues (n=52). We also determined AIB1 gene copy numbers by fluorescence in situ
      hybridization in a subset of cases. RESULTS: In normal pancreas ducts, we rarely
      found detectable levels of AIB1 mRNA or protein (<6% of the samples). In
      pancreatitis and low-grade intraepithelial neoplasia, we found an increased
      frequency of AIB1 expression (>14 and >23%, respectively) relative to normal
      tissues (P < 0.01). Adenocarcinoma, as well as high-grade intraepithelial
      neoplasia, showed increased levels as well as the highest frequency of AIB1
      expression with >65% of samples positive for mRNA and protein (P < 0.0001
      relative to the other groups). An increased copy number of the AIB1 gene,
      observed in 37% of cancers, may account for a portion of the increase in
      expression. CONCLUSIONS: AIB1 overexpression is frequent in pancreatic
      adenocarcinoma and its precursor lesions. On the basis of its rate-limiting role
      for the modulation of growth factor signals, we propose a major role of AIB1 in
      the multistage progression of pancreatic cancer.

PMID- 15448001
TI  - Hierarchical clustering analysis of tissue microarray immunostaining data
      identifies prognostically significant groups of breast carcinoma.
AB  - Prognostically relevant cluster groups, based on gene expression profiles, have
      been recently identified for breast cancers, lung cancers, and lymphoma. Our aim
      was to determine whether hierarchical clustering analysis of multiple
      immunomarkers (protein expression profiles) improves prognostication in patients
      with invasive breast cancer. A cohort of 438 sequential cases of invasive breast
      cancer with median follow-up of 15.4 years was selected for tissue microarray
      construction. A total of 31 biomarkers were tested by immunohistochemistry on
      these tissue arrays. The prognostic significance of individual markers was
      assessed by using Kaplan-Meier survival estimates and log-rank tests. Seventeen
      of 31 markers showed prognostic significance in univariate analysis (P < or =
      0.05) and 4 markers showed a trend toward significance (P < or = 0.2).
      Unsupervised hierarchical clustering analysis was done by using these 21
      immunomarkers, and this resulted in identification of three cluster groups with
      significant differences in clinical outcome. chi2 analysis showed that expression
      of 11 markers significantly correlated with membership in one of the three
      cluster groups. Unsupervised hierarchical clustering analysis with this set of 11
      markers reproduced the same three prognostically significant cluster groups
      identified by using the larger set of markers. These cluster groups were of
      prognostic significance independent of lymph node metastasis, tumor size, and
      tumor grade in multivariate analysis (P=0.0001). The cluster groups were as
      powerful a prognostic indicator as lymph node status. This work demonstrates that
      hierarchical clustering of immunostaining data by using multiple markers can
      group breast cancers into classes with clinical relevance and is superior to the
      use of individual prognostic markers.

PMID- 15448002
TI  - Met proto-oncogene and insulin-like growth factor binding protein 3
      overexpression correlates with metastatic ability in well-differentiated
      pancreatic endocrine neoplasms.
AB  - Pancreatic endocrine neoplasms are neoplastic proliferations of islet cells or
      islet cell precursors and are capable of secreting a variety of synthetic
      products, including insulin, glucagon, gastrin, and vasoactive intestinal
      peptide. The biological behavior of pancreatic endocrine neoplasms is often
      unpredictable, and there are few reliable histopathologic criteria reliably
      correlating with metastatic ability. We have used the Affymetrix U133 GeneChip
      set (HG_U133 A and B; Affymetrix; Santa Clara, CA) representing approximately
      33,000 characterized transcripts to examine global gene expression profiles from
      well-differentiated nonmetastatic (n=5) and metastatic (n=7) pancreatic endocrine
      neoplasms to determine molecular markers that predict disease progression.
      Microarray hybridization data were normalized using the GeneLogic GeneExpress
      Software System to identify differentially up- and down-regulated genes in
      metastatic versus nonmetastatic pancreatic endocrine neoplasms. Using a 3-fold
      change in gene expression as a threshold, we have identified 65 overexpressed and
      57 underexpressed genes in metastatic pancreatic endocrine neoplasms as compared
      with nonmetastatic pancreatic endocrine neoplasms. Several classes of genes,
      including growth factors and growth factor-related molecules (IGFBP1, IGFBP3, and
      MET), developmental factors (TBX3 and MEIS2), cytoskeletal factors (beta 1
      tubulin and ACTN2), cholesterol homeostasis mediators (LRP5, SLC27A2, and RXRG),
      intracellular signaling pathway mediators (DYRK1A, PKIB, and AK2),
      methyltransferases (MGMT and GAMT), and DNA repair and regulatory molecules
      (CHEK1 and ZNF198), were identified as differentially over- or underexpressed via
      this method. Immunohistochemical validation of microarray data were performed for
      two overexpressed genes, namely, the met proto-oncogene (MET) and insulin-like
      growth factor binding protein 3 (IGFBP3) with tissue microarrays of nonmetastatic
      (n=24) and metastatic (n=15) pancreatic endocrine neoplasms. Increased expression
      of IGFBP3 was confirmed in metastatic versus nonmetastatic pancreatic endocrine
      neoplasms (12 of 15, 80% versus 10 of 24, 42%), as well as in lymph node (6 of 7,
      86%) and liver (9 of 9, 100%) metastases. Similarly, overexpression of MET was
      confirmed in metastatic versus nonmetastatic pancreatic endocrine neoplasms (5 of
      15, 33% versus 4 of 24, 17%), as well as in lymph node metastases (4 of 7, 57%)
      and liver metastases (5 of 9, 56%). The majority of genes that demonstrated
      altered expression has not been previously identified as differentially expressed
      in metastatic pancreatic endocrine neoplasm lesions and may therefore represent
      newly identified molecules in the progression of these lesions.

PMID- 15448003
TI  - Characterization of mutator phenotype in familial colorectal cancer patients not
      fulfilling amsterdam criteria.
AB  - PURPOSE: Although the mutator phenotype, including genetic and epigenetic
      alterations of the mismatch repair (MMR) system, seems to be pronounced in
      familial colorectal cancer, there have been few integrative studies comprising
      the entire mutator pathway. This study was done to identify the entire mutator
      pathway determining risk factors in patients with familial colorectal cancer not
      fulfilling the Amsterdam criteria. EXPERIMENTAL DESIGN: We consecutively
      recruited 134 colorectal cancer patients with a family history of accompanying
      cancers. Patients with hereditary nonpolyposis colorectal cancer meeting the
      Amsterdam criteria, familial adenomatous polyposis, or those receiving
      preoperative radiotherapy were excluded. Mutator phenotype was assessed by
      assaying microsatellite instability (MSI) at 24 markers, hMLH1-promoter
      methylation, mutations at MMR genes (hMLH1, hMSH2, hMSH6, and hPMS2), and immune
      staining of MMR proteins (hMLH1, hMSH2, hMSH6, hPMS1, and hPMS2). RESULTS: Of the
      208 cancers in first-degree and/or second-degree relatives of patients,
      colorectal and gastric cancers (81%) were most common. Of the 134 proband
      colorectal cancers, 23 (17%) were MSI in high level, and 32 (24%) were MSI in low
      level. MMR alterations, including known polymorphism and splicing substitution,
      were identified in eight patients (6%). Twenty-eight tumors with mutator
      phenotype were further identified by hMLH1-promoter methylation and/or loss of
      MMR protein expression. In 51 tumors (38%), mutator phenotype was associated with
      right-sided colon cancer (P < 0.001) and younger age at onset (P=0.032), but the
      number of patients with a mutator phenotype did not differ with respect to
      inheritance patterns of accompanying cancers, either successive or horizontal
      transmission (P=0.815). Familial impact value, which differentially associated
      the degree of relatives with all accompanying cancers, effectively discriminated
      MSI in high level from microsatellite stable/MSI in low level tumors. CONCLUSION:
      Familial colorectal cancer may be associated with multiple occurrences of
      colorectal or accompanying cancers inherited by dominant or recessive
      transmission. MMR gene mutations, however, are less associated with mutator
      phenotype in familial colorectal cancer.

PMID- 15448004
TI  - The fibroblast growth factor receptor-4 Arg388 allele is associated with prostate
      cancer initiation and progression.
AB  - PURPOSE: Increased expression of fibroblast growth factors that can activate the
      fibroblast growth factor receptor-4 (FGFR-4) occurs in a substantial fraction of
      human prostate cancers in vivo. A germline polymorphism of the FGFR-4 gene
      resulting in expression of arginine at codon 388 (Arg388) is associated with
      aggressive disease in patients with breast and colon cancer. We therefore sought
      to determine whether the FGFR-4 Arg388 allele was associated with prostate cancer
      incidence and/or the occurrence of aggressive disease. EXPERIMENTAL DESIGN: The
      FGFR-4 genotype of men undergoing radical prostatectomy and controls of the same
      race was determined and the genotype correlated with clinical and pathologic
      markers of disease aggressiveness. PNT1A cell lines expressing predominantly the
      FGFR-4 Arg388 or Gly388 allele were established, and cell migration and
      invasiveness of these cells were assessed by a wounding assay and by quantitative
      determination of invasion through Matrigel. Expression of urokinase-type
      plasminogen activator receptor was determined by quantitative RT-PCR and enzyme
      linked immunoabsorption assay. RESULTS: Homozygosity for the FGFR-4 Arg388 allele
      is strongly associated with the occurrence of prostate cancer in white men. The
      presence of the FGFR-4 Arg388 allele is also correlated with the occurrence of
      pelvic lymph node metastasis and biochemical (prostate-specific antigen)
      recurrence. Expression of FGFR-4 Arg388 in immortalized prostatic epithelial
      cells results in increased cell motility and invasion through Matrigel and was
      associated with increased expression of urokinase-type plasminogen activator
      receptor. CONCLUSION: The FGFR-4 Arg388 allele is associated with both an
      increased incidence and clinical aggressiveness of prostate cancer and results in
      changes in cellular motility and invasiveness in immortalized prostate epithelial
      cells consistent with the promotion of metastasis.

PMID- 15448005
TI  - The antimetastatic role of thrombomodulin expression in islet cell-derived tumors
      and its diagnostic value.
AB  - Islet cell tumors, endocrine neoplasm arising from pancreatic islets of
      Langerhans, are histologically difficult to diagnose as benign or malignant.
      Molecular markers are associated with the clinical characteristics that most of
      insulinoma are usually benign tumors, whereas other islet cell tumors are
      malignant but have not been identified. In this context, we newly found that an
      endothelial anticoagulant thrombomodulin was expressed in the normal islet beta
      cells and insulinoma, but not of other islet components or noninsulinoma islet
      cell tumors. Clinically, all of the subjects (n=15) of the insulinoma group
      showed no metastasis together with thrombomodulin expression in the lesions,
      whereas the other islet cell tumor groups showed a high incidence of metastasis
      (82%) and a low expression rate of thrombomodulin (6%). To examine the functional
      role of thrombomodulin, especially regarding the clinical characteristics of
      islet cell tumors, we tested the effect of exogenous thrombomodulin
      overexpression on cell adhesiveness and proliferation using MIN6 insulinoma cell
      line. In cell-based experiments, thrombomodulin overexpression reduced cell
      proliferation and enhanced Ca2+-independent cell aggregation, possibly through
      direct interaction with neural cell adhesion molecule. Taken together, these
      results are suggesting that thrombomodulin may act as antimetastatic molecule of
      insulinomas. In addition, thrombomodulin is a clinically useful molecular marker
      not only for identifying beta-cell-origin islet cell tumors (i.e., insulinomas)
      but also for predicting disease prognosis of islet cell tumors.

PMID- 15448006
TI  - Tumor suppressor gene promoter hypermethylation in serum of breast cancer
      patients.
AB  - PURPOSE: Breast cancer is the most common malignancy in American women and the
      second leading cause of death from cancer. The genetic and epigenetic alterations
      that initiate and drive cancer can be used as targets for detection of neoplasia
      in bodily fluids. Tumor cell-specific aberrant promoter hypermethylation can be
      detected in nipple aspirate and ductal lavage from breast cancer patients. In
      this study, we examine serum, a more readily accessible bodily fluid known to
      contain neoplastic DNA from individuals with cancer, for methylation-based
      detection of breast neoplasia. EXPERIMENTAL DESIGN: We examined the promoter
      methylation status of three normally unmethylated biologically significant cancer
      genes, RAS association domain family protein 1A (RASSF1A), adenomatous polyposis
      coli (APC), and death-associated protein kinase (DAP-kinase), by sensitive
      methylation-specific PCR in 34 breast tumor and paired preoperative serum DNA.
      The 34 patients comprised 7 ductal carcinoma in situ (CIS), 3 lobular CIS, 5
      stage I and 15 stage II to IV invasive ductal carcinomas, and 4 invasive lobular
      carcinomas. Normal and benign tissue and serum control DNA were also examined to
      determine the specificity of hypermethylation. RESULTS: Hypermethylation of one
      or more genes was found in 32 of 34 (94%) breast tumor DNA. APC was
      hypermethylated in 15 of 34 (47%), RASSF1A in 22 of 34 (65%), and DAP-kinase in
      17 of 34 (50%) tumors. Twenty-six (76%) of the corresponding serum DNA were
      positive for promoter hypermethylation, including ductal CIS, lobular CIS, stage
      I disease, and lobular carcinoma patients. No hypermethylation of APC, RASSF1A,
      or DAP-kinase was observed in serum DNA from normal healthy women and patients
      with inflammatory breast disease or nonneoplastic breast tissue specimens. A gene
      unmethylated in the tumor DNA was always found to be unmethylated in the matched
      serum DNA (100% specificity). CONCLUSIONS: Tumor cell specific promoter
      hypermethylation of APC, RASSF1A, and DAP-kinase is present in ductal CIS,
      lobular CIS, and all grades and stages of invasive breast cancer.
      Hypermethylation can be detected by methylation-specific PCR analysis in serum
      DNA from patients with preinvasive and early-stage breast cancer amenable to
      cure. If confirmed in additional studies, hypermethylation-based screening of
      serum, a readily accessible bodily fluid, may enhance early detection of breast
      cancer.

PMID- 15448007
TI  - The prognostic value of BCAR1 in patients with primary breast cancer.
AB  - PURPOSE: BCAR1, the human homologue of the rat p130Cas protein, was identified in
      a functional screen for human breast cancer cell proliferation resistant to
      antiestrogen drugs. Here, we study the prognostic value of quantitative BCAR1
      levels in a large series of breast cancer specimens. EXPERIMENTAL DESIGN: A
      specific ELISA was developed to measure BCAR1 protein levels in 2593 primary
      breast tumor cytosols. Tumor levels of BCAR1 were correlated with relapse-free
      survival (RFS) and overall survival (OS) and compared with collected data on
      urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor 1
      (PAI-1). RESULTS: In tumor cytosols, BCAR1 protein levels varied between 0.02 and
      23 ng/mg protein. BCAR1 levels exhibited a positive correlation with steroid
      hormone receptor levels, age and menopausal status, and uPA and PAI-1 levels. The
      level of BCAR1 (continuous or categorized as low, intermediate, or high) was
      inversely related with RFS and OS time. Multivariate analysis showed that BCAR1
      levels contributed independently to a base model containing the traditional
      prognostic factors for both RFS and OS (both P < 0.0001). When added together
      with uPA and PAI-1 in the multivariate model, BCAR1 contributed independently of
      PAI-1 and was favored over uPA. Interaction tests allowed for additional analyses
      of BCAR1 protein levels in clinically relevant subgroups stratified by nodal and
      menopausal status. CONCLUSIONS: The quantitative BCAR1 protein level represents a
      prognostic factor for RFS and OS in primary breast cancer, independent of the
      traditional prognostic factors and the other novel marker PAI-1.

PMID- 15448008
TI  - Expression of uncoupling protein-2 in human colon cancer.
AB  - PURPOSE: Cancer cell survival depends on adaptive mechanisms that include
      modulation of oxidative stress. One such mechanism may be via up-regulation of
      uncoupling protein-2 (UCP2), a mitochondrial inner membrane anion carrier
      recently found to provide cytoprotection in nontumor cells by acting as a sensor
      and negative regulator of reactive oxygen species production. We hypothesized
      that UCP2 expression may be increased in colon cancer as part of tumor
      adaptation. EXPERIMENTAL DESIGN: UCP2 expression was characterized by real-time
      polymerase chain reaction and Western blotting using paired human colon
      adenocarcinoma and peritumoral specimens. Oxidant production was characterized by
      tissue malondialdehyde levels. Tissue microarrays constructed of 107 colon
      adenocarcinomas as well as representative specimens of hyperplastic polyps and
      tubular adenomas were used for UCP2 immunohistochemistry. RESULTS: UCP2 mRNA and
      protein levels were 3- to 4-fold higher in adenocarcinomas, and UCP2 mRNA levels
      showed significant correlation with increased tumor tissue malondialdehyde
      contents. Immunohistochemistry on tissue microarrays showed positive staining for
      UCP2 in most adenocarcinomas (86.0%); positive staining for UCP2 was seen less
      often in tubular adenomas (58.8%) and rarely seen in hyperplastic polyps (11.1%).
      CONCLUSIONS: UCP2 expression is increased in most human colon cancers, and the
      level of expression appears to correlate with the degree of neoplastic changes.
      These findings may foster the idea that UCP2 is part of a novel adaptive response
      by which oxidative stress is modulated in colon cancer.

PMID- 15448009
TI  - Prognostic significance of TP53 tumor suppressor gene expression and mutations in
      human osteosarcoma: a meta-analysis.
AB  - PURPOSE: Various studies examining the relationship between tumor suppressor
      protein TP53 overexpression and/or TP53 gene mutations and the response to
      chemotherapy and clinical outcome in patients with osteosarcoma have yielded
      inconclusive results. The purpose of the current study was to evaluate the
      relation of TP53 status with response to chemotherapy and/or clinical outcome in
      osteosarcoma. EXPERIMENTAL DESIGN: We conducted a meta-analysis of 16 studies
      (n=499 patients) that evaluated the correlation between TP53 status and
      histologic response to chemotherapy and 2-year survival. Data were synthesized in
      summary receiver operating characteristic curves and with summary likelihood
      ratios (LRs) and risk ratios. RESULTS: The quantitative synthesis showed that
      TP53 status is not a prognostic factor for the response to chemotherapy. The
      positive LR was 1.21 (95% confidence interval, 0.86-1.71), and the negative LR
      was 0.91 (95% confidence interval, 0.77-1.07). There was no significant between
      study heterogeneity. TP53-positive status tended to be associated with a worse 2
      year survival, but the overall results were not formally statistically
      significant. The association was formally significant in studies that clearly
      stated that measurements were blinded to outcomes (risk ratio, 2.05; 95%
      confidence interval, 1.23-3.44), and in studies using reverse transcription-PCR
      for evaluating TP53 alterations (risk ratio, 1.76; 95% confidence interval, 1.07
      2.91). CONCLUSIONS: TP53 status is not associated with the histologic response to
      chemotherapy in patients with osteosarcoma, whereas TP53 gene alterations may be
      associated with decreased survival.

PMID- 15448010
TI  - p53 expression as a prognostic marker in inflammatory breast cancer.
AB  - PURPOSE: Inflammatory breast cancer (IBC) is a rare and aggressive form of breast
      cancer. Nuclear expression of p53 protein in breast cancer correlates with more
      aggressive tumors. We retrospectively analyze the expression of p53 as a
      prognostic marker to predict pathological complete response and survival in
      patients with IBC. EXPERIMENTAL DESIGN: Fifty-nine patients with IBC were treated
      from January 1994 to April 2000. Forty-eight patients were included. Diagnostic
      core biopsies were taken before treatment was started. Expression of hormone
      receptors and p53 was determined by immunohistochemistry. All patients received
      an anthracycline-based regimen preoperatively; 22 patients (46%) also received
      paclitaxel. Forty-four patients (92%) achieved an objective clinical response and
      underwent mastectomies. RESULTS: Median age at diagnosis was 48 years. Thirty
      patients (63%) had hormone receptor-negative tumors. Twenty-eight patients (58%)
      had p53-positive tumors, and 20 patients (42%) had p53-negative tumors. Nine
      patients (19%) achieved a pathological complete response. At a median follow-up
      of 77 months, 28 recurrences (58%) and 26 deaths (54%) had occurred. Patients
      with p53-positive tumors were younger (P=0.02) and tended to have lower 5-year
      progression-free survival rates (35% versus 55%; P=0.3) and overall survival
      rates (44% versus 54%; P=0.4). CONCLUSIONS: This retrospective analysis
      demonstrates that nuclear p53 protein expression may represent an adverse
      prognostic marker in IBC and may provide a valuable tool for selecting treatment
      for this aggressive disease.

PMID- 15448011
TI  - Antiangiogenic therapy of cerebral melanoma metastases results in sustained tumor
      progression via vessel co-option.
AB  - PURPOSE: In the brain, tumors may grow without inducing angiogenesis, via co
      option of the dense pre-existent capillary bed. The purpose of this study was to
      investigate how this phenomenon influences the outcome of antiangiogenic therapy.
      EXPERIMENTAL DESIGN: Mice carrying brain metastases of the human, highly
      angiogenic melanoma cell line Mel57-VEGF-A were either or not treated with
      different dosages of ZD6474, a vascular endothelial growth factor (VEGF) receptor
      2 tyrosine kinase inhibitor with additional activity against epidermal growth
      factor receptor. Effect of treatment was evaluated using contrast-enhanced
      magnetic resonance imaging (CE- MRI) and (immuno)morphologic analysis. RESULTS:
      Placebo-treated Mel57-VEGF-A brain metastases evoked an angiogenic response and
      were highlighted in CE-MRI. After treatment with ZD6474 (100 mg/kg), CE-MRI
      failed to detect tumors in either prevention or therapeutic treatment regimens.
      However, (immuno)histologic analysis revealed the presence of numerous, small,
      nonangiogenic lesions. Treatment with 25 mg/kg ZD6474 also resulted in efficient
      blockade of vessel formation, but it did not fully inhibit vascular leakage,
      thereby still allowing visualization in CE-MRI scans. CONCLUSIONS: Our data show
      that, although angiogenesis can be effectively blocked by ZD6474, in vessel-dense
      organs this may result in sustained tumor progression via co-option, rather than
      in tumor dormancy. Importantly, blocking VEGF-A may result in undetectability of
      tumors in CE-MRI scans, leading to erroneous conclusions about therapeutic
      efficacy during magnetic resonance imaging follow-up. The maintenance of VEGF-A
      induced vessel leakage in the absence of neovascularization at lower ZD6474 doses
      may be exploited to improve delivery of chemotherapeutic agents in combined
      treatment regimens of antiangiogenic and chemotherapeutic compounds.

PMID- 15448012
TI  - Analysis of antitumor activity of an interleukin-13 (IL-13) receptor-targeted
      cytotoxin composed of IL-13 antagonist and Pseudomonas exotoxin.
AB  - We have shown previously that a chimeric fusion protein composed of human
      interleukin-13 (IL-13) and Pseudomonas exotoxin (PE), termed IL-13 cytotoxin
      (IL13-PE38), is specifically cytotoxic to various cancer cell lines and primary
      cell cultures derived from a variety of solid cancers. In addition, we have shown
      that IL-13 mutant IL-13E13K, in which glutamic acid (E) residue at position 13 of
      IL-13 molecule was substituted by a lysine (K), is a powerful antagonist of IL-13
      and binds to IL-13 receptor with a higher affinity compared with wild-type IL-13.
      In this study, we have generated an IL-13 cytotoxin IL13E13K-PE38, in which IL-13
      antagonist is fused to PE to determine whether this molecule has improved
      cytotoxicity to tumor cells compared with wild type (wt)IL13-PE38. Highly
      purified IL13E13K-PE38 was tested in various tumor cell lines including seven
      glioblastoma multiforme cell lines to compare its binding to the cells, in vitro
      cytotoxicity, in vivo antitumor activity, and safety in mouse model with wtIL13
      PE38. IL13E13K-PE38 bound to U251MG and IL-13Ralpha2 chain-transfected tumor cell
      lines with 3 to 10 times higher affinity compared with wtIL13-PE38. However,
      IL13E13K-PE38 did not show higher cytotoxicity compared with wtIL13-PE38 in
      glioblastoma multiforme or any other cell lines tested. The antitumor activity of
      IL13E13K-PE38, when administered intraperitoneally to nude mice bearing U251
      tumors, was also similar to wtIL13-PE38. Some improvement in antitumor activity
      was observed when lower doses of IL13E13K-PE38 were injected intratumorally in
      subcutaneous tumors. These results indicate that in general, IL13E13K-PE38
      mediates similar cytotoxicity and antitumor activity to wtIL13-PE38 despite its
      improved binding affinity to IL-13 receptors.

PMID- 15448013
TI  - Reversal of the malignant phenotype of gastric cancer cells by inhibition of RhoA
      expression and activity.
AB  - PURPOSE: The small GTPase RhoA has been implicated in the regulation of cell
      morphology, motility, and transformation, but the role of RhoA protein in the
      carcinogenesis of gastric cancer remains unclear. In the present study, we have
      analyzed the expression status of the RhoA protein in human gastric cancer cells
      and tissues and investigated the possible involvement of RhoA in regulating the
      malignant phenotype of gastric cancer cells. EXPERIMENTAL DESIGN: RhoA expression
      was analyzed by immunohistochemistry and Western blot in gastric cancer tissues
      and cell lines. The RhoA-specific small interfering RNA (siRNA) vector was
      designed and constructed. We examined the role of RhoA in the malignant phenotype
      of gastric cancer cells by using siRNA knockdown and dominant-negative RhoA
      mutant suppression of endogenous RhoA activity. RESULTS: RhoA was found
      frequently overexpressed in gastric cancer tissues and cells compared with normal
      tissues or gastric epithelial cells. RhoA-specific siRNA could specifically and
      stably reduce RhoA expression up to 90% in AGS cells. Both RhoA-specific siRNA
      and dominant-negative RhoA expressions could significantly inhibit the
      proliferation and tumorigenicity of AGS cells and enhance chemosensitivity of the
      cancer cells to Adriamycin and 5-fluorouracil. CONCLUSION: RhoA may play a
      critical role in the carcinogenesis of gastric cancer, and the interference of
      RhoA expression and/or activity could provide a novel avenue in reversing the
      malignant phenotype of gastric cancer cells.

PMID- 15448014
TI  - Enhancement of the antibody-dependent cellular cytotoxicity of low-fucose IgG1 Is
      independent of FcgammaRIIIa functional polymorphism.
AB  - PURPOSE: The most common polymorphic variant of Fcgamma receptor type IIIa
      (FcgammaRIIIa), FcgammaRIIIa-158F, has been associated with inferior clinical
      responses to anti-CD20 chimeric IgG1 rituximab compared with FcgammaRIIIa-158V.
      As we previously found that removal of fucose residues from the oligosaccharides
      of human IgG1 results in enhanced antibody-dependent cellular cytotoxicity, we
      compared the effects of the FcgammaRIIIa gene (FCGR3A) polymorphism on normal and
      low-fucose versions of rituximab on antibody-dependent cellular cytotoxicity.
      EXPERIMENTAL DESIGN: The polymorphism at position 158 of FcgammaRIIIa was
      determined for the peripheral blood mononuclear cells (PBMCs) of 20 healthy
      donors. The PBMCs were then used as effector cells to compare the antibody
      dependent cellular cytotoxicity of rituximab and a low-fucose version, KM3065.
      The contributions of the different cell types within the PBMC to antibody
      dependent cellular cytotoxicity were examined. RESULTS: We found KM3065-mediated
      antibody-dependent cellular cytotoxicity was increased 10 to 100-fold compared
      with rituximab for each of the 20 donors. In contrast to rituximab, KM3065
      antibody-dependent cellular cytotoxicity enhancement was similar for both FCGR3A
      alleles and thus independent of genotype. In addition, antibody-dependent
      cellular cytotoxicity of both KM3065 and rituximab requires natural killer cells
      but not monocytes nor polymorphonuclear cells. The antibody-dependent cellular
      cytotoxicity (ADCC) of each of the 20 donors correlated with the natural killer
      cell numbers present in the PBMCs. Importantly, using KM3065, the ADCC mediated
      by effector cells bearing the lower affinity variant FcgammaRIIIa-158F was
      significantly increased compared with rituximab-mediated ADCC using effector
      cells bearing the higher affinity FcgammaRIIIa-158V receptors. CONCLUSIONS: The
      use of low-fucose antibodies might improve the therapeutic effects of anti-CD20
      therapy for all patients independent of FcgammaRIIIa phenotype beyond that
      currently seen with even the most responsive patients.

PMID- 15448015
TI  - Characterization of a folate transporter in HeLa cells with a low pH optimum and
      high affinity for pemetrexed distinct from the reduced folate carrier.
AB  - Studies were undertaken to characterize a low pH transport activity in a reduced
      folate carrier (RFC)-null HeLa-derived cell line (R5). This transport activity
      has a 20-fold higher affinity for pemetrexed (PMX; Kt, approximately 45 nmol/L)
      than methotrexate (MTX; Kt, approximately 1 micromol/L) with comparable Vmax
      values. The Ki values for folic acid, ZD9331, and ZD1694 were approximately 400
      600 nmol/L, and the Ki values for PT523, PT632, and trimetrexate were >50
      micromol/L. The transporter is stereospecific and has a 7-fold higher affinity
      for the 6S isomer than the 6R isomer of 5-formyltetrahydrofolate but a 4-fold
      higher affinity for the 6R isomer than the 6S isomer of dideazatetrahydrofolic
      acid. Properties of RFC-independent transport were compared with transport
      mediated by RFC at low pH using HepG2 cells, with minimal constitutive low pH
      transport activity, transfected to high levels of RFC. MTX influx Kt was
      comparable at pH 7.4 and pH 5.5 (1.7 versus 3.8 micromol/L), but Vmax was
      decreased 4.5-fold. There was no difference in the Kt for PMX (approximately 1.2
      micromol/L) or the Ki for folic acid (approximately 130 micromol/L) or PT523 (
      approximately 0.2 micromol/L) at pH 7.4 and pH 5.5. MTX influx in R5 and HepG2
      transfectants at pH 5.5 was trans-stimulated in cells loaded with 5
      formyltetrahydrofolate, inhibited by Cl- (HepG2-B > R5), Na+ independent, and
      uninhibited by energy depletion. Hence, RFC-independent low pH transport activity
      in HeLa R5 cells is consistent with a carrier-mediated process with high affinity
      for PMX. Potential alterations in protonation of RFC or the folate molecule as a
      function of pH do not result in changes in affinity constants for antifolates.
      Whereas both activities at low pH have similarities, they can be distinguished by
      folic acid and PT523, agents for which they have very different structural
      specificities.

PMID- 15448016
TI  - Identification of the fenretinide metabolite 4-oxo-fenretinide present in human
      plasma and formed in human ovarian carcinoma cells through induction of
      cytochrome P450 26A1.
AB  - PURPOSE: The synthetic retinoid fenretinide (4-HPR) exhibits preventive and
      therapeutic activity against ovarian tumors. An unidentified polar metabolite was
      previously found in 4-HPR-treated subjects and in A2780 human ovarian carcinoma
      cells continuously treated with 4-HPR (A2780/HPR). The metabolite and the enzyme
      involved in its formation in tumor cells are herein identified. EXPERIMENTAL
      DESIGN: The metabolite was identified by mass spectrometry in A2780/HPR cell
      extracts and in plasma from 11 women participating in a phase III trial and
      treated with 200 mg/d 4-HPR for 5 years. The expression of proteins involved in
      retinoid metabolism and transport, cytochrome P450 26A1 (CYP26A1), cellular
      retinol-binding protein I (CRBP-I), and cellular retinoic acid-binding protein I
      and II (CRABP-I, CRABP-II) were evaluated in tumor cells by reverse transcription
      PCR and Western blot analyses. Overexpression of CYP26A1 and retinoic acid
      receptors (RARs) in A2780 cells were obtained by cDNAs transfection. RESULTS: The
      polar metabolite was 4-oxo-N-(4-hydroxyphenyl)retinamide (4-oxo-4-HPR) i.e., an
      oxidized form of 4-HPR with modification in position 4 of the cyclohexene ring. 4
      oxo-4-HPR plasma levels were slightly lower (0.52 +/- 0.17 micromol/L) than those
      of the parent drug (0.84 +/- 0.53 micromol/L) and of the already identified
      metabolite N-(4-methoxyphenyl)retinamide (1.13 +/- 0.85 micromol/L). In A2780/HPR
      cells continuously treated with 4-HPR and producing 4-oxo-4-HPR, CYP26A1 and CRBP
      I were markedly up-regulated compared with A2780 untreated cells. In A2780 cells,
      not producing 4-oxo-4-HPR, overexpression of CYP26A1 caused formation of 4-oxo-4
      HPR, which was associated with no change in 4-HPR sensitivity. Moreover, the
      addition of 4-oxo-4-HPR to A2780 cells inhibited cell proliferation. Elevated
      levels of CYP26A1 protein and metabolism of 4-HPR to 4-oxo-4-HPR were found in
      A2780 cells transfected with RARbeta and to a lesser extent in those transfected
      with RARgamma. CONCLUSIONS: A new metabolite of 4-HPR, 4-oxo-4-HPR, present in
      human plasma and in tumor cells, has been identified. The formation of this
      biologically active metabolite in tumor cells was due to CYP26A1 induction and
      was influenced by RAR expression. Moreover evidence was provided that 4-HPR up
      modulates the expression of CRBP-I transcript, which is lost during ovarian
      carcinogenesis.

PMID- 15448017
TI  - Innovations and challenges in renal cancer: consensus statement from the first
      international conference.

PMID- 15448018
TI  - Genetic basis of cancer of the kidney: disease-specific approaches to therapy.
AB  - Studies during the past two decades have shown that kidney cancer is not a single
      disease; it is made up of a number of different types of cancer that occur in
      this organ. Clear cell renal carcinoma is characterized by mutation of the VHL
      gene. The VHL gene product forms a heterotrimeric complex with elongin C, elongin
      B, and Cul-2 to target hypoxia-inducible factors 1 and 2alpha for ubiquitin
      mediated degradation. VHL-/- clear cell renal carcinoma overexpresses epidermal
      growth factor receptor and transforming growth factor alpha. Both hypoxia
      inducible factor 1alpha and the epidermal growth factor receptor are potential
      therapeutic targets in clear cell renal carcinoma. Studies of the hereditary form
      of renal cell carcinoma (RCC) associated with hereditary papillary renal
      carcinoma (HPRC) determined that the c-Met proto-oncogene on chromosome 7 is the
      gene for HPRC and for a number of sporadic papillary RCCs. The HPRC c-Met
      mutations are activating mutations in the tyrosine kinase domain of the gene. The
      gene for a new form of hereditary RCC (Birt Hogg Dube syndrome) associated with
      cutaneous tumors, lung cysts, and colon polyps or cancer has recently been
      identified. Studies are currently under way to determine what type of gene BHD is
      and how damage to this gene leads to kidney cancer. Individuals affected with
      hereditary leiomyomatosis renal cell carcinoma are at risk for the development of
      cutaneous leiomyomas, uterine leiomyomas (fibroids), and type 2 papillary RCC.
      The HLRC gene has been found to be the Krebs cycle enzyme, fumarate hydratase.
      Studies are under way to understand the downstream pathway of this cancer gene.

PMID- 15448019
TI  - The von Hippel-Lindau tumor suppressor gene and kidney cancer.
AB  - The von Hippel-Lindau tumor suppressor gene (VHL), which resides on chromosome
      3p25, is mutated or silenced in >50% of sporadic clear cell renal cell
      carcinomas. Germ-line VHL mutations give rise to VHL disease, which is
      characterized by an increased risk of blood vessel tumors (hemangioblastomas) and
      renal cell carcinomas. In this setting, VHL inactivation gives rise to
      premalignant renal cysts. Additional genetic alterations are presumably required
      for conversion of these cysts to renal cell carcinomas. Restoration of VHL
      function in VHL-/- renal cell carcinomas is sufficient to inhibit tumorigenesis
      in vivo. On the basis of these and other data, VHL appears to be a critical
      gatekeeper with respect to the development of renal cell carcinoma. The VHL gene
      product, pVHL, is the substrate recognition module of an E3 ubiquitin ligase that
      targets the hypoxia-inducible factor (HIF) for destruction in the presence of
      oxygen. Hypoxic cells, or cells lacking pVHL, accumulate high levels of HIF,
      which activates the transcription of a variety of genes, including vascular
      endothelial growth factor, platelet-derived growth factor B, and transforming
      growth factor alpha. We have demonstrated that inhibition of HIF is necessary and
      sufficient for tumor suppression by pVHL in renal cell carcinoma nude mouse
      xenograft assays. This provides a rationale for treating VHL-/- renal cell
      carcinoma with inhibitors of HIF or its downstream targets. Genotype-phenotype
      correlations in VHL disease suggest, however, that pVHL has targets in addition
      to HIF. Elucidating these targets should provide a more complete picture of how
      pVHL suppresses tumor growth.

PMID- 15448020
TI  - Molecular markers for early detection of renal carcinoma: investigative approach.
AB  - Molecular markers for renal cell carcinoma could guide early detection of
      localized disease in defined populations at high risk for the disease or early
      disease recurrence after nephrectomy for renal cell carcinoma. In addition,
      sensitive and specific markers may provide surrogate end points for clinical
      trials of treatment and/or disease prevention. Powerful techniques of genomic and
      proteomic analysis of human renal carcinoma cell lines, tumor samples, and
      biological fluids, such as plasma and urine, obtained from patients with renal
      cell carcinoma, are likely to identify candidate markers. Careful selection among
      early candidate markers and further testing in independent patient populations
      are required for marker validation.

PMID- 15448021
TI  - Prognostic factors for survival of patients with stage IV renal cell carcinoma:
      memorial sloan-kettering cancer center experience.
AB  - Prospective identification of patients with stage IV renal cell carcinoma more
      likely to benefit from cytokine therapy could be used as a stratification factor
      in Phase III trials and in risk-directed therapy. The relationship between
      pretreatment clinical features and survival was evaluated in patients treated in
      Phase II and III clinical trials for metastatic renal cell carcinoma at the
      Memorial Sloan-Kettering Cancer Center. The first analysis was performed in 670
      patients treated with cytokines or chemotherapy, and a multivariate model was
      created to predict survival. Studies that followed addressed four topics: (1) the
      survival of patients given interferon alpha as first-line therapy, (2) a
      comparison of survival for patients treated with chemotherapy versus cytokine
      therapy, (3) survival of patients with nonclear cell histologic features, and (4)
      survival of patients treated with a second-line therapy. Prognostic models based
      on pretreatment clinical and laboratory variables can help identify patients more
      likely to benefit from standard therapies, as well as assist in the
      interpretation of drug effectiveness in Phase II clinical trials. Investigations
      into new prognostic factors based on tumor biology are needed and of high
      priority.

PMID- 15448022
TI  - Tissue array-based predictions of pathobiology, prognosis, and response to
      treatment for renal cell carcinoma therapy.
AB  - Renal cell carcinoma is the most lethal of the common urologic malignancies, with
      approximately 40% of patients eventually dying of cancer progression.
      Approximately one third of patients present with metastatic disease, and up to
      40% treated for localized disease have a recurrence. Historically, clinical
      factors have been used as prognostic markers for patients with renal cell
      carcinoma. Recent advances in the understanding of the pathogenesis, behavior,
      and molecular biology of renal cell carcinoma have paved the way for developments
      that may enhance early diagnosis, better predict tumor prognosis, and improve
      survival for renal cell carcinoma patients. Furthermore, reliable predictive
      factors are essential for the stratification of patients into clinically
      meaningful categories, which can be used to provide patients with counseling
      regarding prognosis, select treatment modalities, and determine eligibility for
      clinical trials. This has led to the creation of integrated staging systems that
      predict outcome by combining pathological and clinical variables. Although
      staging has been improved with the development of integrated systems, molecular
      tumor markers are expected to revolutionize the staging of renal cell carcinoma
      in the future. The development of methods based on gene and tissue arrays has
      created a powerful tool for evaluating hundreds to thousands of tumors
      simultaneously with histologic, immunohistochemical, and chromosomal analyses.
      Gene array analysis permits rapid molecular profiling, and tissue arrays enable
      the analysis of protein expression profiles on specimens to determine their
      potential clinical significance and role in renal cell carcinoma biology. This
      article reviews the tissue array-based predictors of pathobiology, prognosis,
      response to treatment, and potential molecular targets for therapy of renal cell
      carcinoma.

PMID- 15448023
TI  - Prognostic factors in patients with advanced renal cell carcinoma: development of
      an international kidney cancer working group.
AB  - The identification of prognostic factors in patients with metastatic renal cell
      carcinoma represents an area of increasing interest. Multiple publications
      identifying pertinent clinical and laboratory variables have appeared since 1986.
      The current study of 353 patients with advanced disease treated at The Cleveland
      Clinic from 1987 to 2002 was conducted to additionally assess and validate a
      model proposed recently by investigators from Memorial Sloan-Kettering Cancer
      Center. The data presented are similar to those reported previously, which
      demonstrated that patients with metastatic renal cell carcinoma can be
      categorized into good-, intermediate-, and poor-risk groups, using readily
      available clinical factors. Additionally, comparability of patients in this
      database to a group treated recently in France was assessed. These two groups
      appear similar in their distribution of various clinical factors and survival.
      Finally, a group of international investigators has been developed to provide a
      comprehensive database of >4,000 patients with metastatic renal cell carcinoma to
      provide and validate a single model that can be used to predict survival. This
      project is now under way.

PMID- 15448024
TI  - Gene expression profiling of renal cell carcinoma.
AB  - Renal cell carcinoma (RCC) is a histologically diverse disease, with variable and
      often unpredictable clinical behavior. The prognosis worsens dramatically with
      the onset of clinical metastasis, and current regimens of systemic therapy yield
      only modest benefits for metastatic RCC. Gene expression profiling is a promising
      technique for refining the diagnosis and staging of RCC, as well as for
      highlighting potential therapeutic targets. We review the recent advances in
      expression profiling of RCC and discuss the clinical and biological insights
      obtained from these studies.

PMID- 15448025
TI  - Laparoscopic and partial nephrectomy.
AB  - Radical nephrectomy is the gold standard curative operation for patients with
      localized renal cell carcinoma (RCC). Since its introduction in 1990,
      laparoscopic radical nephrectomy is being increasingly done at numerous
      institutions worldwide. In the hands of experienced laparoscopic urological
      surgeons and with adherence to established principles of open radical
      nephrectomy, laparoscopic radical nephrectomy is now a standard of care for
      patients with T1-3a N0 M0 RCC. Intermediate-term outcome data indicate equivalent
      cancer-free survival to open radical nephrectomy in such cases. Nephron-sparing
      surgery (NSS) is now an established approach for patients with localized RCC when
      there is a clinically relevant need to preserve renal function. NSS is also
      indicated in patients with a single, small, unilateral, localized RCC when the
      opposite kidney is completely normal. The technical success rate with NSS for RCC
      is excellent, and long-term patient survival free of cancer is comparable with
      that obtained after radical nephrectomy. We recently reviewed the results of NSS
      in 107 patients with localized sporadic RCC treated at the Cleveland Clinic
      before 1988 who were followed up for a minimum of 10 years. Long-term
      preservation of renal function was achieved in 93% of patients, and the 10-year
      cancer specific survival rate was 73%. Although open surgical partial nephrectomy
      remains the gold standard for nephron-sparing treatment of RCC, laparoscopic
      partial nephrectomy is now available in selected cases. The optimal indications
      for laparoscopic NSS are in patients with a relatively small and peripheral renal
      tumor. In such cases, laparoscopic NSS is proving to be an effective, minimally
      invasive therapeutic approach with respect to renal functional outcome, with
      additional advantages of reduced postoperative narcotic use, earlier hospital
      discharge, and a faster convalescence. The laparoscopic approach is associated
      with longer warm renal ischemia time, more major intraoperative complications,
      and more postoperative urological complications. Continued efforts are required
      to develop laparoscopic renal hypothermia techniques and to facilitate intrarenal
      suturing while minimizing the warm ischemia time.

PMID- 15448026
TI  - Review of radiofrequency ablation for renal cell carcinoma.
AB  - This review will discuss how minimally invasive, image-guided radiofrequency (RF)
      tumor ablation [i.e., coagulating tumor using short-duration heating (<15
      minutes) by directly applying temperatures >50 degrees C via needle electrodes]
      is being incorporated as a clinical tool for the treatment of renal cell
      carcinoma. RF ablation has been used to treat focal liver tumors. Potential
      benefits of this thermal therapy include reduced morbidity and mortality compared
      with standard surgical resection and the ability to treat nonsurgical patients.
      More recently, this technique has been introduced to treat focal renal tumors,
      particularly incidental lesions smaller than 3 cm in elderly patients and those
      with comorbid conditions. Other uses have included treatment in patients with von
      Hippel-Lindau syndrome and other diseases that predispose patients to multiple
      renal carcinomas, where renal parenchymal preservation is desired. Techniques,
      complications, and results will be discussed. Additionally, strategies that we
      are currently studying to improve RF outcomes and enable the potential treatment
      of larger tumors will be addressed. Most notably, recent data on increased
      coagulation achieved by combining RF ablation with antivascular/antiangiogenic
      therapies, such as arsenic trioxide, that reduce blood flow and promote heat
      retention are provided.

PMID- 15448027
TI  - Debulking nephrectomy in metastatic renal cancer.
AB  - Up to one third of patients with renal cell carcinoma will present with
      metastatic disease, and 20 to 40% of those with clinically localized disease will
      eventually be found to have metastatic involvement. Prognosis continues to be
      guarded for this population, with a 2-year survival of only 10 to 30%. Although
      advances are being made in the medical management of renal cell carcinoma, the
      role of surgery in the treatment algorithm is also being additionally refined.
      Palliative surgery either via nephrectomy or metastasectomy has a role in certain
      well-selected patients. There are also data to support total metastasectomy at
      the time of either nephrectomy or recurrence in a small subset of patients with
      minimal, resectable metastases. More controversial is the idea of cytoreductive
      nephrectomy as an adjunct to immunotherapy. Recent phase III trials indicate that
      nephrectomy may play an important role in management of metastatic renal cell
      carcinoma in conjunction with cytokine-based immunotherapy. Nephrectomy is also
      an essential component of tumor-based vaccine and adoptive immunotherapy
      protocols and may play a role in other novel therapies.

PMID- 15448028
TI  - Update on the role of interleukin 2 and other cytokines in the treatment of
      patients with stage IV renal carcinoma.
AB  - Immunoreactive cytokines have been the mainstay of treatment of renal cancer for
      the past 15 years. Most research has focused on interferon alpha (IFN-alpha) and
      interleukin 2 (IL-2). IFN-alpha has been shown in Phase III studies to produce a
      modest survival advantage over inactive or non-IFN-containing regimens. Its
      general tolerability, multiple proposed mechanisms of action, and familiarity
      have prompted IFN-alpha to be studied in combination with a variety of agents
      with potential activity against renal cell carcinoma. These various studies may
      justify an increased role for IFN-alpha in the treatment of renal cancer in the
      foreseeable future. High-dose bolus IL-2 remains the only treatment for stage IV
      renal cancer approved by the United States Food and Drug Administration. Food and
      Drug Administration approval was granted in 1992 based on the ability of this
      agent to produce durable complete responses in a small number of patients.
      Unfortunately, the toxicity, expense, and restricted accessibility of high-dose
      IL-2 make it a poor standard. Regimens involving lower doses of IL-2 either alone
      or in combination with IFN-alpha have generally produced fewer tumor regressions
      of less overall quality. Recent efforts have focused on trying to identify
      factors predictive of response to IL-2 therapy so that this treatment could be
      limited to those most likely to benefit.

PMID- 15448029
TI  - Dendritic cell-tumor fusion vaccines for renal cell carcinoma.
AB  - Renal cell carcinoma is a malignant disease that demonstrates resistance to
      standard chemotherapeutic agents. A promising area of investigation is the use of
      cancer vaccines to educate host immunity to specifically target and eliminate
      malignant cells. Dendritic cells (DCs) are potent antigen-presenting cells that
      are uniquely effective in generating primary immune responses. DCs that are
      manipulated to present tumor antigens induce antitumor immunity in animal models
      and preclinical human studies. A myriad of strategies have been developed to
      effectively load tumor antigen onto DCs, including the introduction of individual
      peptides, proteins, or tumor-specific genes, as well as the use of whole tumor
      cells as a source of antigen. A promising approach for the design of cancer
      vaccines involves the fusion of whole tumor cells with DCs. The DC-tumor fusion
      presents a spectrum of tumor-associated antigens to helper and cytotoxic T-cell
      populations in the context of DC-mediated costimulatory signals. In animal
      models, vaccination with DC-tumor fusions resulted in protection from tumor
      challenge and regression of established metastatic disease. We have conducted
      phase 1 dose escalation studies in which patients with metastatic breast and
      renal cancer underwent vaccination with DC-tumor fusions. Twenty-three patients
      underwent vaccination with autologous DC-tumor fusions. Vaccination was well
      tolerated without substantial treatment-related toxic effects. Immunologic
      responses and disease regression were observed in a subset of patients. Future
      studies will explore the effect of DC maturation and cytokine adjuvants on
      vaccine potency.

PMID- 15448030
TI  - Nonmyeloablative transplantation: an allogeneic-based immunotherapy for renal
      cell carcinoma.
AB  - High-dose chemotherapy followed by autologous hematopoietic stem cell
      transplantation has been explored as a method to enhance the efficacy of
      chemotherapy for advanced solid tumors. The failure of autologous hematopoietic
      stem cell transplantation to prolong survival in patients with metastatic solid
      tumors has sparked interest recently in studies exploring the potential of
      allogeneic hematopoietic stem cell transplantation for such patients. Allogeneic
      hematopoietic stem cell transplantation is widely accepted as a potent form of
      immunotherapy capable of curing patients with chemotherapy-refractory hematologic
      malignancies. However, it was not until the end of the 20th century that
      investigators initiated trials to test the potential of allogeneic hematopoietic
      stem cell transplantation as immunotherapy in malignancies of epithelial origin.
      Early pilot trials have established proof-of-principle that graft-versus-tumor
      effects can induce complete or partial remission in some treatment-refractory
      metastatic solid tumors. In this review, we discuss the rationale for pilot
      trials investigating the potential of nonmyeloablative allogeneic hematopoietic
      stem cell transplantation in advanced cytokine-refractory renal cancer,
      highlighting the preliminary success, limitations, and future clinical directions
      of this approach.

PMID- 15448031
TI  - Effect of renal cell carcinomas on the development of type 1 T-cell responses.
AB  - PURPOSE: We reported that in renal cell carcinoma patients with active disease, T
      cell reactions to the tumor-associated antigens MAGE-6 and EphA2 are highly
      skewed toward TH2-type cytokine responses [interleukin (IL) 5]. Herein, we
      determined whether tumor-derived products, including gangliosides isolated from
      renal cell carcinoma patients, participate in the down-regulation of type 1 T
      cell responses. EXPERIMENTAL DESIGN: T cells from healthy volunteers or renal
      cell carcinoma patients were cultured in the presence and absence of supernatants
      derived from renal cell carcinoma explants or with gangliosides isolated from
      those tumor supernatants. T cells were stimulated or not with either autologous
      dendritic cells pulsed with superantigen (Staphylococcus enterotoxin B) or with
      phorbol 12-myristate 13-acetate and ionomycin and then were assessed for type 1
      or type 2 responses (cytokine production and gene expression) and apoptosis.
      RESULTS: Tumor supernatants efficiently inhibited the TH1-type responses
      [interferon (IFN) gamma] of T cells stimulated with either S. enterotoxin B or
      phorbol 12-myristate 13-acetate and ionomycin but had no inhibitory effect on
      activated T-cell production of type 2 cytokines (IL-4, IL-5, and IL-10).
      Likewise, IFN-gamma mRNA and protein production were inhibited when T cells were
      cocultured with either renal cell carcinoma supernatant-derived gangliosides or a
      commercial source of purified GD1a. It was also determined that gangliosides
      impair type 1 responses by inducing apoptosis of activated T cells. CONCLUSIONS:
      We propose that renal cell carcinoma-derived tumor products such as gangliosides
      can induce a type 2 bias in antitumor immunity by initiating apoptosis in the IFN
      gamma-producing type 1 effector cells. This represents a relevant mechanism by
      which renal cell carcinoma can inhibit protective antitumor immunity.

PMID- 15448032
TI  - Bevacizumab for patients with metastatic renal cancer: an update.
AB  - Most clear cell renal cell cancer (RCC) is caused by biallelic loss of the von
      Hippel-Lindau gene. One consequence of this loss is up-regulation of vascular
      endothelial growth factor via a pathway involving accumulation of hypoxia
      inducible factor. Vascular endothelial growth factor, a potent angiogenic factor,
      is secreted by many human cancers, but clear cell RCC as a group produces
      particularly high levels and has a highly vascular histologic appearance. In a
      randomized, placebo-controlled, double-blind trial, we tested the use of a
      neutralizing antibody to vascular endothelial growth factor, bevacizumab, in
      patients with metastatic RCC. At 3 or 10 mg/kg every 2 weeks, toxic effects were
      minimal, with hypertension and proteinuria the most substantial events. There
      were four partial responses (10% response rate) and a highly substantial
      prolongation of time to tumor progression in patients who received the higher
      dose of bevacizumab. With a crossover design and very sensitive criteria for
      disease progression, no difference in survival was shown. Four patients have been
      undergoing long-term bevacizumab therapy without tumor progression for 3 to 5
      years. Three have substantial proteinuria but retain normal renal function. A
      small pilot trial combining bevacizumab and thalidomide showed no unexpected
      toxic effects. Future trials should consider combination therapies and strategies
      in which patients are treated through initial disease progression with
      antiangiogenic agents such as bevacizumab.

PMID- 15448033
TI  - Tyrosine kinase inhibitors in renal cell carcinoma.
AB  - Current standard treatments for patients with metastatic (stage IV) renal cell
      carcinoma involve both surgical removal of tumors and treatment with biological
      agents such as interleukin 2 and/or IFN-alpha. Unfortunately, such approaches are
      inadequate for most patients with stage IV disease; the result is a median time
      to progression of 2 to 4 months and an overall survival of 6 to 17 months.
      Standard chemotherapy has been uniformly disappointing in this disorder. It is
      clear that new therapies are needed to approach these patients. Recently, a
      greater understanding of cancer genetics has led to the successful development of
      novel therapeutics directed against targets linked to specific types of cancer.
      During the past decade, researchers have identified the von Hippel-Lindau (VHL)
      gene as an important tumor suppressor in clear cell carcinoma of the kidney.
      Elucidation of the VHL gene product (pVHL) and its regulation of hypoxia
      inducible factor signaling have created a potential genetic basis for growth
      factor-targeted strategies in this disease. This review will focus on the
      potential growth factor targets in clear cell carcinoma, their relation to VHL
      and hypoxia-inducible factor, and the clinical challenges that face their
      development.

PMID- 15448034
TI  - Novel antiangiogenic therapies for renal cell cancer.
AB  - Renal cell cancer remains a disease for which highly effective therapy for the
      majority of patients with metastatic disease is lacking. The biology of clear
      cell carcinomas and their association with mutations of the von Hippel-Lindau
      gene and its resultant increased expression of vascular endothelial growth factor
      (VEGF) make angiogenesis a potentially pathophysiologic mechanism for tumor
      development. As a result, the use of antiangiogenic therapy is an intriguing
      concept for the treatment of renal cell cancer. Various agents, aside from the
      inhibitors of VEGF, have been studied, including thalidomide, low-dose
      interferon, and novel antiangiogenic agents such as the thrombospondin-1
      mimetics. Use of these agents has been associated with some degree of objective
      response or prolonged stabilization of disease, and their true value needs to be
      assessed in ongoing prospective studies. Combinations of antiangiogenic agents
      either with other similarly acting drugs or as a component of a "cocktail" with
      other noncytotoxic therapies should be explored in this patient population.

PMID- 15448035
TI  - Mammalian target of rapamycin inhibition.
AB  - The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that has
      been increasingly recognized as key to the regulation of cell growth and
      proliferation. mTOR either directly or indirectly regulates translation
      initiation, actin organization, tRNA synthesis, ribosome biogenesis, and many
      other key cell maintenance functions, including protein degradation and
      transcription functions. Inhibition of mTOR blocks traverse of the cell cycle
      from the G1 to S phase. Preclinical data show inhibition of tumor growth in a
      number of cell lines and xenograft models. Clinical trials are ongoing. In
      metastatic renal cell cancer, both tumor regression and prolonged stabilization
      have been noted. mTOR inhibition appears to be a key pathway that may be useful
      in antitumor therapy. Renal cell cancer may be particularly susceptible through
      both the translation inhibition pathway and pathways that enhance HIF-1alpha gene
      expression, a factor believed to stimulate growth in metastatic renal cell
      cancer. Additional clinical trials that use agents that inhibit mTOR are ongoing.

PMID- 15448036
TI  - Kinase inhibition with BAY 43-9006 in renal cell carcinoma.
AB  - BAY 43-9006 is an oral inhibitor of CRAF, wild-type BRAF, mutant V599E BRAF,
      vascular endothelial growth factor receptor (VEGFR) 2, VEGFR3, mVEGFR2, FLT-3,
      platelet-derived growth factor receptor, p38, and c-kit among other kinases. A
      Phase I study of BAY 43-9006 identified 400 mg orally twice daily as the
      recommended Phase II dose. The Phase II results of a study of BAY 43-9006 at 400
      mg orally twice daily were particularly interesting in patients with renal cell
      carcinoma. Data from the first 41 patients with renal cell carcinoma showed that
      30% of patients had stable disease (defined as between 25% reduction and 25%
      growth), 40% had responded (defined as >25% reduction), and 30% had progressed.
      Disease could be stabilized for periods in excess of a year. Some lesions became
      cystic and could actually enlarge while developing a low attenuation core. This
      phenomenon is recognized in the treatment of gastrointestinal stromal tumors with
      imatinib mesylate. The toxic effects of BAY 43-9006 were manageable and included
      hypertension, edema, diarrhea, hand and foot syndrome, rash, and hair loss where
      the rash involved the scalp. There was an impression of tachyphylaxis such that
      patients who required a dose reduction could be restored to full dose after a few
      months. A Phase III randomized, placebo-controlled trial of BAY 43-9006 has
      started for patients whose renal cell carcinoma has progressed within 6 months of
      immunotherapy. Combination studies with interferon, interleukin 2, bevacizumab,
      and chemotherapy are under consideration. The therapeutic targets of BAY 43-9006
      in renal cell carcinoma remain unclear. Unlike melanoma, BRAF mutations have not
      been found in renal cell carcinoma. Other candidate targets include VEGFR2 and
      VEGFR3.

PMID- 15448037
TI  - Therapeutic options for variant renal cancer: a true orphan disease.
AB  - Variant or nonclear cell renal cell cancer is a rare disease constituting only
      approximately 5% to 8% of the metastatic renal cell cancer population.
      Pathological criteria for the three main variant subtypes, papillary,
      chromophobe, and collecting duct, have been specified. Nonetheless, there may be
      subtypes within these variants, many poorly differentiated tumors cannot be
      reliably classified, and expertise in recognizing specific subtypes is not
      widespread. Expression analysis and other molecular techniques are beginning to
      clarify and standardize the pathological classification scheme. Because these
      classifications are relatively new and the number of patients with any one
      subtype is limited, little is known about appropriate therapies for patients with
      metastatic disease. Retrospective series strongly suggest that immunotherapy is
      not effective in any nonclear cell subtype. Case reports suggest that cytotoxic
      chemotherapy used for transitional cell cancers may be helpful in patients with
      collecting duct cancers. A central registry of patients with variant renal cell
      cancer should be created in which response to various therapies is recorded. Such
      a registry could provide support for a more formal multi-institutional study
      investigating a specific drug or regimen.

PMID- 15448038
TI  - Skeletal complications in patients with bone metastases from renal cell carcinoma
      and therapeutic benefits of zoledronic acid.
AB  - Bone metastases in patients with renal cell carcinoma are associated with a high
      risk of skeletal complications. Therefore, a subset analysis of a larger clinical
      trial was performed to determine the efficacy of zoledronic acid in renal cell
      carcinoma patients. Patients with bone metastases from solid tumors other than
      breast or prostate cancer (n=773) were randomized to receive zoledronic acid or
      placebo via 15-minute infusion every 3 weeks for 9 months. Patients were
      monitored for skeletal-related events, which were defined as pathological
      fracture, spinal cord compression, radiotherapy, or surgery to bone. Among the
      subset of 74 patients with renal cell carcinoma, 46 patients were treated with 4
      mg of zoledronic acid or placebo. Significantly fewer patients treated with 4 mg
      zoledronic acid had a skeletal-related event (37% versus 74% for placebo,
      P=0.015), and zoledronic acid significantly prolonged the time to first skeletal
      related event (median not reached at 9 months versus 72 days for placebo;
      P=0.006). Zoledronic acid significantly reduced the annual incidence of skeletal
      related events by approximately 21% (mean 2.68 versus 3.38 events per year for
      placebo, P=0.014) and significantly reduced the risk of developing a skeletal
      related event by 61% compared with placebo (risk ratio=0.394, P=0.008) by
      multiple event analysis. Median time to progression of bone lesions was also
      significantly extended with zoledronic acid treatment (P=0.014). Zoledronic acid
      is the first bisphosphonate to significantly reduce skeletal morbidity and
      significantly prolong time to bone lesion progression in patients with bone
      metastases from renal cell carcinoma.

PMID- 15448041
TI  - A new look for volume 8.

PMID- 15448042
TI  - Iced 2000.

PMID- 15448043
TI  - Education of deaf children and the politics of recognition.
AB  - The ideological basis for education of deaf children has changed during the last
      few decades. In Norway, the new curriculum is emphasizing bilingual and
      bicultural ideas. In many ways, this can be regarded as an example of what
      Charles Taylor calls the "politics of recognition." Taking an excerpt of an
      interview with a deaf student as a point of departure, this article discusses
      problems when heavily emphasizing a cultural approach.

PMID- 15448044
TI  - From Screening to Early Identification and Intervention: Discovering Predictors
      to Successful Outcomes for Children With Significant Hearing Loss.
AB  - This article summarizes the research findings from a longitudinal study of the
      language, speech, and social-emotional development of children who are deaf and
      hard of hearing, all of whom have hearing parents. This series of studies, from
      1994 to the present, investigated predictors of successful developmental
      outcomes. The article provides information about how the findings of these
      studies relate to the existing literature. A description of the Colorado Home
      Intervention Program (CHIP) in which the participants were enrolled is also
      provided. During the course of these investigations, universal newborn hearing
      screening programs were established in Colorado, changing the age of
      identification of hearing loss and initiation into intervention in this program
      geared to families with infants and toddlers, birth through three years of age,
      from an average of 20 months of age to 2 months of age. Language development is
      positively and significantly affected by the age of identification of the hearing
      loss and age of initiation into intervention services. Both speech development
      and social-emotional variables are highly related to language development.

PMID- 15448045
TI  - The Use of Visual-Tactile Communication Strategies by Deaf and Hearing Fathers
      and Mothers of Deaf Infants.
AB  - This article presents the results of a study comparing deaf and hearing parents
      in the use of visual-tactile communication strategies during interaction with
      their hearing-impaired children between 18 and 24 months of age. The study
      includes 17 deaf and hard-of-hearing children and 33 parents, covering hearing
      mothers (n = 12), hearing fathers (n = 11), deaf mothers (n = 5), and deaf
      fathers (n = 5). The four groups of parents are compared in the use of visual
      tactile communication strategies during free play with their children. Overall
      results show that deaf mothers and deaf fathers differ significantly from hearing
      parents in the use of a visual communication style adapted to the developmental
      communication needs and abilities related to the 18- to 24-month age period. The
      study pays special attention to differences in visual-tactile communication
      strategies according to hearing status, gender, use of languages, and
      communication modes.

PMID- 15448046
TI  - Assessing intentional communication in deaf toddlers.
AB  - This study examines the eliciting potential of two tasks, one for proto
      imperative and another for protodeclarative communicative intentions. The task to
      elicit proto-imperative utterances and the scoring form are partially based on
      Casby and Cumpata's (1986) Protocol for the Assessment of Prelinguistic
      Intentional Communication (PAPIC). However, a number of modifications are
      proposed for use with young deaf children. For the protodeclaratives, a new
      eliciting task called Tac-Tic was created. These tasks were offered to 18
      normally developing profoundly deaf toddlers at the ages of 18, 24, and 30
      months. Results indicate that both tasks possess sufficient eliciting potential
      to measure both the prelinguistic and early linguistic "illocutionary force" of
      profoundly deaf children. Moreover, the new eliciting task Tac-Tic seems to have
      a higher eliciting potential than the corresponding task used in the PAPIC. For
      clinical aims, a more adapted and more efficient scoring form than the one Casby
      and Cumpata used was created.

PMID- 15448047
TI  - Influences of student and family factors on academic outcomes of mainstream
      secondary school deaf students.
AB  - This article considers some of the student and family factors influencing the
      educational achievements of deaf children. It is based on a study of 16-year-old
      deaf students in mainstream schools in England. Findings indicate the complexity
      of interpreting statistical results, especially on the effect of degree of
      hearing loss. The discussion addresses the specific question of why this factor
      is often reported as not significant in academic achievement. It also considers
      the surprisingly low effect of family socioeconomic status, speculates on the
      size of the "school effect" in deaf education, and considers the coding of data.

PMID- 15448048
TI  - Survey of residential and day schools for deaf students in the United States that
      identify themselves as bilingual-bicultural programs.
AB  - The purpose of this survey was to determine how many residential and day schools
      for deaf and hard-of-hearing students in the United States described themselves
      as bilingual-bicultural (BiBi) programs and to describe characteristics of those
      programs related to initial implementation, whether a single language (e.g.,
      English or ASL) is promoted as the first language (L1) and the language of
      instruction for all deaf students, how English is conveyed conversationally to
      deaf students, the quality of ASL abilities of BiBi instructional and support
      staff; general characteristics of the curriculum and the specific reading and
      bicultural components of the curriculum; and characteristics of research being
      conducted to establish the efficacy of BiBi methods. Ninety-one percent (n = 71)
      of the 78 day and residential schools listed in the 1998 Directory of the
      American Annals of the Deaf participated in the survey, with 19 schools
      identifying themselves as BiBi. These included 16 residential schools and 3 day
      schools. Depending on the source for numbers of students in residential and day
      schools at the time of the survey, between 36% and 40% of students were in
      programs that identified themselves as BiBi. Sixteen of the programs reported
      becoming a BiBi program between 1989 and 1994 and only three after 1994. Of the
      19 programs, 37% reported use of manually coded English (MCE) for conveying
      English to the students. Fluency in ASL of instructional and support staff
      varied, with 47% of the programs reporting that no more than half of the
      instructional staff were fluent in ASL and 68% of the programs reporting that no
      more than half of the support staff were fluent. Only 21% of the 19 programs
      reported having a formal BiBi curriculum with annual goals and suggested
      materials and procedures for teachers. Research implications of these data are
      discussed.

PMID- 15448049
TI  - The ABCs of New Zealand Sign Language: Aerial Spelling.
AB  - Aerial spelling is the term given here for the way many deaf people in New
      Zealand, especially the elderly, manually represent letters of the alphabet. It
      is simply a system using the index finger to write letter(s) "in the air" and is
      an integral part of New Zealand Sign Language (NZSL). Unfortunately, recent
      research into NZSL is either dismissive of it or fails to acknowledge it. This
      article describes aerial spelling and discusses its nature, as well as its
      indifferent treatment in current literature.

PMID- 15448050
TI  - Predictors of reading delay in deaf adolescents: the relative contributions of
      rapid automatized naming speed and phonological awareness and decoding.
AB  - Deaf readers often fail to achieve age-appropriate reading levels. In hearing
      children, two cognitive factors correlated with reading delay are phonological
      awareness and decoding (PAD) and rapid automatized naming (RAN) of visual
      material. In this study we explored the contribution of these factors to reading
      and reading delay in a sample of deaf students (N = 49, mean age 13 years) whose
      reading age (RA) was around 7 years. Although PAD performance was poor in the
      deaf students compared with RA-matched hearing controls, it nevertheless
      correlated with their RA. Whether tested in sign or speech, RAN was much faster
      in the deaf group than in RA-matched hearing controls but showed no direct
      relationship with reading level or reading delay. We conclude that in contrast to
      PAD, which is a factor in both deaf and hearing reading achievement, RAN may be
      only indirectly related to reading in deaf students.

PMID- 15448051
TI  - The importance of processing automaticity and temporary storage capacity to the
      differences in comprehension between skilled and less skilled college-age deaf
      readers.
AB  - The prevalence of low comprehension among deaf readers has been documented for
      decades, yet the problem persists. Progress has been hampered by uncertainty
      regarding which aspects of reading competence ought to be the primary focus of
      concerted instructional efforts. This article examines whether temporary storage
      capacity and/or processing automaticity may explain the difference in
      comprehension between skilled and less skilled adult deaf readers. Temporary
      storage capacity is the ability to maintain separate bits of information in
      current memory while they are being processed. Processing automaticity is the
      ability to complete certain basic operations of reading, such as recognizing
      individual words and chunking sets of words into meaningful phrases, with a
      minimum of intentional mental effort. In this study one group of deaf adults
      reading at the college level and another reading at the 5th-grade level completed
      a battery of experimental tasks that generated multiple indicators of storage
      capacity and automaticity. These included the reading span task of Daneman and
      Carpenter (1980), an analogous addition span task, two measures of phonological
      processing, and a sentence-reading task that varied the demands on temporary
      storage and processing automaticity. Results suggest that skilled readers do not
      command an exceptionally large temporary storage capacity, nor do less skilled
      readers suffer from deficient storage capacity. The indicators of processing
      automaticity suggest, however, that less skilled readers must invest
      significantly more conscious mental effort than skilled readers to complete basic
      operations of reading. These findings are applied to theory related to (a) the
      nature of the breakdowns in comprehension faced by readers with low automaticity,
      (b) the interaction of low automaticity with other obstacles to comprehension,
      and (c) the design of practice experiences to increase the automaticity and
      ultimately the comprehension of deaf readers.

PMID- 15448052
TI  - Rhyme generation in deaf students: the effect of exposure to cued speech.
AB  - This study compares the rhyme-generation ability of deaf participants with severe
      to profound hearing losses from cued speech (CS) and non-cued speech (NCS)
      backgrounds with a hearing comparison group for consistent orthography-to
      phonology (O-P) rhyming elements, or rimes (e.g., -ail in sail is always
      pronounced the same), and inconsistent orthography-to-phonology (I-O-P) rhyming
      elements where the orthographic rime (e.g., -ear) has different pronunciations in
      words such as bear, and rear. Rhyming accuracy was better for O-P target words
      than for I-O-P target words. The performance of the deaf participants from CS
      backgrounds, although falling between that of the hearing and the NCS groups, did
      not differ significantly from that of the hearing group. By contrast, the
      performance of the NCS group was lower than that of the hearing group. Hearing
      and CS participants produced more orthographically different responses (e.g.,
      blue-few), whereas participants from the NCS group produced more responses that
      are orthographically similar (e.g., blue-true), indicating that the hearing and
      CS groups rely more on phonology and the NCS group more on spelling to generate
      rhymes. The results support the use of cued speech for developing phonological
      abilities of deaf students to promote their reading abilities.

PMID- 15448053
TI  - Deaf persons of asian american, Hispanic american, and african american
      backgrounds: a study of intraindividual diversity and identity.
AB  - This article explores the ways in which deaf college students who are members of
      minority racial groups think about and describe their identities. In-depth,
      semistructured interviews with 33 deaf students of Asian American, Hispanic
      American, and African American background were analyzed for themes regarding the
      self-reported identities of respondents. Results suggest that each person is a
      constellation of many parts, some of which are stronger than others but any of
      which can be drawn out in response to a particular set of circumstances,
      resulting in a contextual and interactive model of identity. Four factors are
      described as central to this "intraindividual" model: individual characteristics,
      situational conditions, social conditions, and societal conditions. Additionally,
      the model includes a biographical component reflected in changes in identity that
      occur over time. Findings are discussed as they relate to identity theory. The
      article is concluded with recommendations for further research, as well as
      considerations for educators and counselors of deaf minority students.

PMID- 15448054
TI  - Decisions Hispanic families make after the identification of deafness.
AB  - This study examines the decision-making process for Hispanic families living in
      the United States who have a child with a hearing loss. Twenty-nine families in
      four geographical areas shared their experiences in searching for appropriate
      interventions and making choices regarding communication and education. We
      explored the impact of language, culture, minority status, and access to
      information and services on the decision-making process. The results indicate
      that the deliberations of Hispanic parents are often complicated by language and
      cultural barriers and by limited access to information, resources, and a full
      range of options. The communication method chosen tended to be the one
      recommended by professionals, usually a combination of spoken English and sign
      language. Parents frequently expressed the hope that their child would learn
      Spanish as well. These subjects displayed a higher degree of assertiveness in
      obtaining services for their children than other studies have suggested.

PMID- 15448055
TI  - Identity Issues for Hard-of-Hearing Adolescents Aged 11, 13, and 15 in Mainstream
      Setting.
AB  - This study examined identity issues and aspects of the health behaviors of
      mainstreamed hard-of-hearing (HOH) students aged 11, 13, and 15 compared with
      their peers. A sample of 52 HOH students was matched with 470 peers of the same
      age, gender, and ethnicity. A survey based on the World Health Organization
      Health Behaviours of School Aged Children was administered and the results of the
      hearing and the HOH groups compared. Although there were few statistically
      significant differences, there were indications that the HOH students more often
      experienced a sense of loneliness than their hearing peers did. The majority of
      HOH students (55.8%) did not self-identify as having a hearing disability. When
      examined by the willingness to self-identify, the reported frequencies of
      loneliness and bullying were statistically significant. These findings support
      the view that the school experience of a significant number of mainstreamed HOH
      students is not supportive. Those students who do self-identify are physically
      and psychologically more at risk. The reluctance to self-identify may reflect the
      prevalence of negative stigma.

PMID- 15448056
TI  - Factors Affecting Psychosocial Adjustment of Deaf Students.
AB  - Deafness is more than a medical condition. Recent theories have emphasized the
      importance of environmental factors on the psychosocial development of deaf
      children. As part of a larger scale study, this article aims to investigate the
      impact of the following variables on deaf students' psychosocial adjustment in
      Turkey: student-related background and experiential characteristics, parent
      related variables, school-related factors, and teacher-related variables. The
      sample of 1,097 deaf students enrolled in the elementary, secondary, and high
      schools was drawn from 34 schools in 24 cities on a national geographical spread.
      The multiple regression analysis revealed that degree of hearing loss, additional
      handicap, and age at onset of deafness were negatively related to psychosocial
      adjustment of deaf students. However, there was a positive relationship between
      psychosocial variables and some of the independent variables, such as use of
      hearing aids, speech intelligibility, academic achievement, parental hearing
      status, and communication methods used at school. The findings of the study do
      not support a "pathological" view of deafness, suggesting that it was not
      deafness per se but that some environmental factors were also influential on the
      psychosocial adjustment of deaf students.

PMID- 15448057
TI  - Siblings and theory of mind in deaf native signing children.
AB  - We report a study designed to examine the basis of "theory of mind" (ToM)
      reasoning in deaf children who are native signers of British Sign Language. The
      participants were 20 native signers (aged 4-8 years) and their siblings. The
      children were given a measure of the quality of sibling relations together with a
      referential communication test concerning physical representations of objects and
      people. Sibling quality as perceived by siblings predicted children's ToM scores
      over and above age and referential communication. We conclude that the process of
      ToM understanding is linked to positive sibling relations that may permit access
      to knowledge about the inner worlds of beliefs and other mental states.

PMID- 15448058
TI  - Can the Emotion Recognition Ability of Deaf Children be Enhanced? A Pilot Study.
AB  - We evaluated the effectiveness of an 11-lesson psychoeducational program designed
      to enhance the ability of deaf children to understand the emotional experience of
      themselves and other people. The "Funny Faces Program" was provided to 14
      children, aged 9 to 13, with moderate to profound hearing impairments. All
      children were enrolled in an "oral" education program at a school for the deaf.
      Alternate forms of the Emotion Recognition Scales (Dyck, Ferguson, & Shochet,
      2001) were administered at pretest and posttest. Results indicate significant
      increases in emotion vocabulary and emotion comprehension but not in the speed or
      accuracy of emotion recognition (ER), from pretest to posttest. At posttest,
      children whose hearing loss was moderate to severe did not differ from hearing
      children in ER abilities but children with profound hearing loss continued to
      show substantial ability deficits.

PMID- 15448059
TI  - Deaf sex offenders in a prison population.
AB  - Very little is known about deaf sex offenders. This descriptive study of a
      population of 41 deaf sex offenders incarcerated by the state of Texas provides
      information about the prevalence of sexual offenders in the deaf prison
      population, the educational achievement and IQ scores of deaf offenders, and the
      incidence of secondary disabilities in this population. The rate of sexual
      offending by deaf offenders was 4 times the rate of sexual offending by hearing
      offenders with 30% recidivism in the population. Sexual offending by deaf adults
      is discussed in relation to the sexual abuse of deaf children. Sixty-two percent
      of deaf sex offenders were functionally illiterate, a literacy rate considerably
      below the average for deaf adults who remained in school until age 18 or above.
      However, the performance IQs of deaf sex offenders were comparable to those of
      the overall prison population.

PMID- 15448060
TI  - The effect of irrelevant visual input on working memory for sign language.
AB  - We report results showing that working memory for American Sign Language (ASL) is
      sensitive to irrelevant signed input (and other structured visual input) in a
      manner similar to the effects of irrelevant auditory input on working memory for
      speech. Deaf signers were disrupted on serial recall of lists of ASL signs when
      either pseudosigns or moving shapes were presented during a retention interval.
      Hearing subjects asked to recall lists of printed English words did not show
      disruption under the same interference conditions. The results favor models that
      hypothesize modality-specific representations of language within working memory,
      as opposed to amodal representations. The results further indicate that working
      memory for sign language involves visual or quasi-visual representations,
      suggesting parallels to visuospatial working memory.

PMID- 15448061
TI  - Mathematics word problem solving for deaf students: a survey of practices in
      grades 6-12.
AB  - One hundred and thirty-three mathematics teachers of deaf students from grades 6
      12 responded to a survey on mathematics word problem-solving practices. Half the
      respondents were teachers from center schools and the other half from mainstream
      programs. The latter group represented both integrated and self-contained
      classes. The findings clearly show that regardless of instructional setting, deaf
      students are not being sufficiently engaged in cognitively challenging word
      problem situations. Overall, teachers were found to focus more on practice
      exercises than on true problem-solving situations. They also emphasize problem
      features, possibly related to concerns about language and reading skills of their
      students, rather than analytical and thinking strategies. Consistent with these
      emphases, teachers gave more instructional attention to concrete visualizing
      strategies than to analytical strategies. Based on the results of this study, it
      appears that in two of the three types of educational settings, the majority of
      instructors teaching mathematics and word problem solving to deaf students lack
      adequate preparation and certification in mathematics to teach these skills. The
      responses of the certified mathematics teachers support the notion that
      preparation and certification in mathematics makes a difference in the kinds of
      word problem-solving challenges provided to deaf students.

PMID- 15448062
TI  - Deaf college students' comprehension of relational language in arithmetic compare
      problems.
AB  - In this study of deaf college students' performance solving compare word
      problems, relational statements were either consistent or inconsistent with the
      arithmetic operation required for the solutions. The results support the
      consistency hypothesis Lewis and Mayer (1987) proposed based on research with
      hearing students. That is, deaf students were more likely to miscomprehend a
      relational statement and commit a reversal error when the required arithmetic
      operation was inconsistent with the statement's relational term (e.g., having to
      add when the relational term was less than). Also, the reversal error effect with
      inconsistent word problems was magnified when the relational statement was a
      marked term (e.g., a negative adjective such as less than) rather than an
      unmarked term (e.g., a positive adjective such as more than). Reading ability
      levels of deaf students influenced their performance in a number of ways. As
      predicted, there was a decrease in goal-monitoring errors, multiple errors, and
      the number of problems left blank as the reading levels of students increased.
      Contrary to expectations, higher reading skills did not affect the frequency of
      reversal errors.

PMID- 15448063
TI  - Mastery motivation and expressive language in young children with hearing loss.
AB  - We studied the relation between mastery motivation and expressive language in 200
      young children with hearing loss. Hearing mothers assessed their children's
      expressive language (Minnesota Child Development Inventory; Ireton & Thwing,
      1974) and several aspects of mastery motivation including mastery pleasure and
      three components of mastery persistence (gross motor, object oriented, and
      social/symbolic) using the Dimensions of Mastery Motivation Questionnaire (Morgan
      et al., 1992). Simple correlations revealed significant relations between
      expressive language and all mastery motivation scales. When demographic and
      hearing loss variables were entered into a regression equation, only increased
      social/symbolic persistence was significantly related to, and increased object
      oriented persistence was marginally related to, increases in expressive language
      quotients. Expressive language quotients also increased significantly as child
      age and degree of hearing loss decreased and as mothers' ratings of their child's
      general competence increased. In addition, decreases in the age at which the
      child was enrolled in intervention were marginally related to increases in
      expressive language quotients (f =.06).

PMID- 15448064
TI  - Clinical Examination of Three Methods of Teaching Reading Comprehension to Deaf
      and Hard-of-Hearing Students: From Research to Classroom Applications.
AB  - This study shows how to integrate research-based teaching methods in reading
      comprehension with real classroom teaching activities. The performance of 30 male
      (n = 13; mean age = 11.51 years) and female (n = 17; mean age = 12.11 years) deaf
      and hard-of-hearing students from the United Arab Emirates (UAE) was examined
      under three teaching conditions: the key word strategy, modified reciprocal
      teaching, and the basic reading approach. Analyses showed that the key word
      strategy and modified reciprocal teaching significantly enhanced students'
      overall performance in reading comprehension scores. Results revealed that any
      one of these three methods would be adequate for teaching factual information.
      However, results indicated that the key word strategy and modified reciprocal
      teaching would be better for teaching factual information, comprehension, and
      memorization skills than the basic reading approach.

PMID- 15448065
TI  - Using verbal protocols to identify the reading strategies of students who are
      deaf.
AB  - The purpose of this study was to identify the reading strategies used by students
      who are deaf by investigating their self-reported thinking during reading. The
      participants were 10 elementary students attending a residential state school for
      the deaf. After each page of reading a short story, the participants were asked
      to think aloud (or think visibly, in the case of sign language). Analysis of
      these verbal reports indicated that the participants constructed meaning,
      monitored comprehension and activated strategies to improve comprehension, and
      evaluated, but did not demonstrate, each reading strategy within these three
      classifications. They engaged in a considerably greater variety of reading
      strategies for constructing meaning than for the other two classifications.

PMID- 15448066
TI  - Considerations for designing practice for deaf readers.
AB  - Low reading comprehension persists among deaf readers, and recent research
      indicates that low automaticity in recognizing words and parsing sentence
      patterns is a significant source of the difficulty. When a learner does manage to
      gain an insight about some aspect of printed English, there may be limited impact
      on comprehension until the new knowledge can be applied fluently because the
      multiple cognitive demands of reading call for completing basic linguistic
      operations with a minimum of conscious effort. The research literature agrees
      that the route to improved automaticity is effective practice, and, thus,
      practice is also a likely route to increased comprehension. This article presents
      considerations to guide the design of practice for deaf readers. Certain of these
      notions are relatively applied in nature and may shape practice activities
      directly, for example, the discussion of research-based guidelines for tailoring
      the sequence and composition of practice items. Other parts of the discussion,
      such as those related to word recognition, are more theoretical than directive,
      and they imply research hypotheses that can and should be tested empirically. A
      principal point of this article is that without appreciable improvements in
      practice, the reading of many deaf students will remain largely unimproved.

PMID- 15448067
TI  - Computer-Assisted Vocabulary Acquisition: The CSLU Vocabulary Tutor in Oral-Deaf
      Education.
AB  - Deficits in vocabulary have a negative impact on literacy and interpersonal
      interaction for deaf children. As part of an evaluation, an outcomes assessment
      was conducted to determine the effectiveness of a computer-based vocabulary tutor
      in an elementary auditory/oral program. Participants were 19 children, 16
      profoundly deaf and 3 hearing. The vocabulary tutor displays line drawings or
      photographs of the words to be learned while a computer-generated avatar of a
      "talking head" provides synthesized audiovisual speech driven from text. The
      computer system also generates printed words corresponding to the imaged items.
      Through audiovisual reception, children memorized up to 218 new words for
      everyday household items. After 4 weeks, their receptive vocabulary was tested,
      using the avatar to speak the name of each item. Most of the students retained
      more than half of the new words. The freely available vocabulary tutor, whose
      characteristics can be tailored to individual need, can provide a language
      intensive, independent learning environment to supplement classroom teaching in
      content areas.

PMID- 15448068
TI  - Self-esteem scores among deaf college students: an examination of gender and
      parents' hearing status and signing ability.
AB  - Overall, research studies of self-esteem and deafness yield inconsistent
      findings. Some studies indicate a higher incidence of low self-esteem among deaf
      individuals than among hearing individuals (Bat-Chava, 1994; Mulcahy, 1998;
      Schlesinger, 2000). Other findings suggest that one must examine this complex
      phenomenon more closely to understand how deafness influences self-concept and
      self-esteem (Bat-Chava, 2000; Emerton, 1998; Foster, 1998; Munoz-Baell & Ruiz,
      2000; Stone, 1998). This study asked whether self-esteem scores are significantly
      different among deaf college students compared across groups based on gender and
      parents' hearing status and signing ability. The construct of self-esteem was
      measured by the Rosenberg Self-Esteem Scale, administered using an American Sign
      Language-translated videotape. Results revealed that gender, age, and the
      interaction of parent by gender were nonsignificant. However, respondents who had
      at least one deaf parent and signed scored significantly higher than those with
      hearing parents who could not sign and those with hearing parents who could sign.
      Overall, self-esteem scores for all respondents were high. Implications for
      further study are discussed.

PMID- 15448069
TI  - Shielding yourself from the perils of empathy: the case of sign language
      interpreters.
AB  - Cross-cultural exchanges between deaf and hearing persons are replete with
      unintentional misunderstandings and even purposeful acts of oppression. Sign
      language interpreters routinely bear witness to the negative emotional fallout of
      these dynamics on the Deaf consumer. It is largely inevitable-a psychological
      reflex-to experience some degree of empathic pain. One must achieve a healthy
      balance of empathizing enough while shielding oneself from its perils. I describe
      the psychological effects of juxtaposed extremes of affect, projective
      identification, and the dual nature of empathy.

PMID- 15448070
TI  - Assessment of Prelinguistic Behaviors in Deaf Children: Parents as Collaborators.
AB  - This article begins with the rationale for a detailed assessment of prelinguistic
      behaviors in young deaf children. I used a Hebrew adaptation of the parent
      questionnaire developed by Camaioni, Caselli, Volterra, and Luchenti (1992) in
      Italy to collect data on a relatively large heterogeneous Israeli sample of deaf
      participants: 43 deaf children of hearing parents (19 girls and 24 boys) ranging
      in age from 8 to 49 months. Results indicated that prelinguistic behaviors in
      deaf infants resemble only to some extent the theoretical model of prelinguistic
      communication in hearing infants. Unique interrelationships emerged among
      pointing and early noncommunicative behaviors, yet no correlation emerged between
      the use of referential gestures and early words or signs. We analyzed findings
      with respect to the comparison of prelinguistic behavioral characteristics in
      hearing and deaf children and the collaboration with parents in assessing the
      prelinguistic behaviors of their own deaf children.

PMID- 15448071
TI  - Vocabulary Assessment of Deaf and Hard-of-Hearing Children From Infancy Through
      the Preschool Years.
AB  - The purpose of this article is to inform researchers and practitioners about
      potential challenges in the selection, administration, and interpretation of
      results of measures of vocabulary assessment when working with deaf and hard-of
      hearing children. This article reviews methods that can be used to assess
      vocabulary of children through the age of 5 years, including naturalistic
      observation, parent report measures, and standardized vocabulary tests. The
      authors also describe procedures to assess word-learning processes available to
      children to facilitate vocabulary acquisition. General cautions regarding the use
      of assessment tools with deaf and hard-of-hearing children are reviewed, as well
      as cautions for specific assessment measures. Finally, based on available
      research, suggestions are offered regarding what each assessment test can tell us
      about deaf and hard-of-hearing children's vocabulary development.

PMID- 15448072
TI  - Assessment of Language Skills in Young Children with Profound Hearing Loss under
      Two Years of Age.
AB  - This article presents an initial evaluation of a technique known as the Diary of
      Early Language (Di-EL), designed to obtain data about early lexical development
      in young children with profound hearing loss using cochlear implants, hearing
      aids, or both. The validity of the Di-EL, a parent report technique, was examined
      through comparisons with other measures of language development. Lexical data
      reported by parents using the Di-EL was found to agree with that reported by the
      same parents for the same children using the MacArthur Communicative Development
      Inventories (CDI), although some differences in the lexical items were noted.
      Rate of lexical acquisition on the Di-EL was found to correlate highly with that
      measured by the CDI and with expressive language skills as measured by the
      Rossetti Infant Toddler Language Scale, suggesting that the Di-EL is a valid
      measure of early lexical progress. These results are discussed with reference to
      other diary studies, along with research and clinical applications of the Di-EL.

PMID- 15448073
TI  - Hearing Status, Language Modality, and Young Children's Communicative and
      Linguistic Behavior.
AB  - This study examined early pragmatic skill development in a group of 38 children
      with severe or profound hearing loss between 1 and 4 years of age who were
      enrolled in a simultaneous communication (SC) approach to language learning. Both
      their use of intentionally communicative acts and their use of language were
      studied in an analysis of 30-min play sessions between a child and the primary
      caregiver. Results were compared with previously published data from two age
      matched groups: 38 deaf children who were enrolled in oral communication (OC)
      programs and 84 normally hearing (NH) children. All groups showed a significant
      improvement with age in the communicative behaviors measured; therefore, the
      overall trend was toward growth-in all age groups-even when the rates of growth
      differed. By age 3 years, a pattern of communicative function use had emerged in
      all three groups. Patterns exhibited by deaf children in the SC and OC groups
      were similar to each other and to younger NH children but dissimilar to NH age
      mates. Although the use of signed input by normally hearing parents and teachers
      did not serve to ameliorate the profound effects of hearing loss on communication
      development in SC children, it did provide some early advantages. The children in
      SC groups did not exhibit an advantage over children in OC groups in their
      overall frequency of communication or the breadth of their vocabulary but they
      began using words earlier and used mature communicative functions significantly
      more often. Although children in the OC groups did not exhibit a significant
      advantage in the overall amount of speech used, they showed an advantage in the
      breadth of their spoken vocabulary in a conversational setting. Implications for
      early intervention programming are discussed.

PMID- 15448074
TI  - The Language Proficiency Profile-2: Assessment of the Global Communication Skills
      of Deaf Children Across Languages and Modalities of Expression.
AB  - Data are presented from two studies that investigate the developmental trends and
      concurrent validity of a measure of language and communication skills for deaf
      children, the Language Proficiency Profile-2 (LPP-2), developed by Bebko and
      McKinnon (1993). The LPP-2 was designed to evaluate the overall
      linguistic/communicative skills of deaf children, independent of any specific
      language or modality of expression. It focuses on the totality of the children's
      communication skills. Experiment 1 investigated developmental trends of the LPP-2
      for both deaf and hearing children, studying a combined sample of deaf and
      hearing children from the United States and Canada. Experiment 2 investigated the
      relationship between the LPP-2 and two commonly used measures to assess deaf
      children on language development (Preschool Language Scale-3) and early reading
      skills (Test of Early Reading Ability-Deaf/Hard-of-Hearing). Results from the two
      studies indicate that the LPP-2 has good utility not only as a measure of overall
      language development but also as a predictor of achievement for English language
      and early reading skills.

PMID- 15448075
TI  - The Profile of Multiple Language Proficiencies: A Measure for Evaluating Language
      Samples of Deaf Children.
AB  - This article reports the process of creating a developmental measure that
      assesses the multilingual capabilities of deaf children and the problems that
      were encountered. Because deaf children may be using more than one method of
      communication (e.g., sign language skills and spoken language skills), it is
      important to evaluate their skills as completely as possible. In a pilot study,
      we used a nominal scale that assessed language skills based on a single
      continuum, with good English and good American Sign Language (ASL) skills as its
      two extremes and approximately equal skills in both as the midpoint. In the main
      study, a more complete measure was created, the Profile of Multiple Language
      Proficiencies (PMLP). The PMLP uses a single scale that represents the different
      stages of language development that can be observed in both English and ASL. The
      PMLP showed reasonable initial reliability and has good promise as an easy-to-use
      measure of developing language skills in children who use multiple modalities of
      communication. Using the PMLP as a prototype, we discuss some of the issues that
      influence the reliability and validity in evaluating such a scale and how these
      can be overcome or avoided.

PMID- 15448076
TI  - The contribution of phonological awareness and receptive and expressive english
      to the reading ability of deaf students with varying degrees of exposure to
      accurate english.
AB  - This study was planned with the knowledge that the tasks of reading require the
      same acquisition of skills, whether a child is hearing or deaf, monolingual, or
      bilingual. Reading and language research literature was reviewed. Subjects were
      31 deaf students (7.9-17.9 years of age) who attended one of three U.S. programs.
      Performance on 15 language and literacy measures was analyzed. Results were that
      students who scored highest on a passage-comprehension measure also were more
      able (a) to provide synonyms, antonyms, and analogies of read words and phrases,
      (b) to read more listed words, and (c) to substitute one phoneme more correctly
      for another to create new words than were readers with lower scores. Two groups
      of students also were compared: a Longer Exposure to English Group (n = 22) who
      used Signing Exact English (SEE) for 5 years or more and a Shorter Exposure Group
      (n = 8) exposed to SEE for less than 2 years. A correlational analysis revealed
      that there were no significant relationships among 14 background variables with
      the exception of "age of identification of hearing loss," a variable then
      covaried in subsequent analysis of covariance. Students in the Longer Exposure
      Group scored higher on all measures. Significant differences were found between
      groups for short-term memory, receptive and expressive English, and five
      phonological subtests. Mini-case studies and the performance of eight students in
      the Longer Exposure Group who scored lowest on the comprehension measure also are
      discussed.

PMID- 15448077
TI  - Transition for Deaf and Hard-of-Hearing Students: A Blueprint for Change.
AB  - The large and growing number of deaf and hard-of-hearing adults who are "low
      functioning deaf" (LFD), the unmet needs of many young people who are deaf or
      hard of hearing, and the continuing high rates of dropping out argue for a change
      in secondary programming for multiply disabled deaf and hard-of-hearing students
      and for others who are at risk of becoming LFD as adults. The LFD designation
      refers to youth and adults who read at very low levels, whether or not they have
      a second disability in addition to hearing impairment. This article reviews
      research related to transition for adolescents with disabilities as well as those
      who are deaf or hard of hearing. It then offers a case for change, one that, for
      the United States, represents a poignant return to a time past.

PMID- 15448078
TI  - Aerial Spelling and NZSL: A Response to Forman (2003).

PMID- 15448079
TI  - Neuronal glucosensing: what do we know after 50 years?
AB  - Glucosensing neurons are specialized cells that use glucose as a signaling
      molecule to alter their action potential frequency in response to variations in
      ambient glucose levels. Glucokinase (GK) appears to be the primary regulator of
      most neuronal glucosensing, but other regulators almost certainly exist. Glucose
      excited neurons increase their activity when glucose levels rise, and most use GK
      and an ATP-sensitive K(+) channel as the ultimate effector of glucose-induced
      signaling. Glucose-inhibited (GI) neurons increase their activity at low glucose
      levels. Although many use GK, it is unclear what the final pathway of GI neuronal
      glucosensing is. Glucosensing neurons are located in brain sites and respond to
      and integrate a variety of hormonal, metabolic, transmitter, and peptide signals
      involved in the regulation of energy homeostasis and other biological functions.
      Although it is still uncertain whether daily fluctuations in blood glucose play a
      specific regulatory role in these physiological functions, it is clear that large
      decreases in glucose availability stimulate food intake and counterregulatory
      responses that restore glucose levels to sustain cerebral function. Finally,
      glucosensing is altered in obesity and after recurrent bouts of hypoglycemia, and
      this altered sensing may contribute to the adverse outcomes of these conditions.
      Thus, although much is known, much remains to be learned about the physiological
      function of brain glucosensing neurons.

PMID- 15448080
TI  - Intracerebroventricular neuropeptide Y infusion precludes inhibition of glucose
      and VLDL production by insulin.
AB  - Recent evidence demonstrates that hypothalamic insulin signaling is required for
      inhibition of endogenous glucose production. The downstream mechanisms that are
      responsible for the effects of hypothalamic insulin receptor activation on
      hepatic fuel flux remain to be determined. To establish whether downregulation of
      neuropeptide Y (NPY) release by insulin is mandatory for its capacity to suppress
      glucose production, we examined the effects of a continuous
      intracerebroventricular (ICV) infusion of NPY (10 microg/h for 3-5 h) on glucose
      flux during a hyperinsulinemic-euglycemic clamp in mice. We also evaluated the
      effects of ICV NPY administration on free fatty acid and glycerol flux and VLDL
      production in this experimental context. In basal conditions, none of the
      metabolic parameters was affected by NPY infusion. In hyperinsulinemic
      conditions, peripheral glucose disposal was not different between vehicle- and
      NPY-infused animals. In contrast, hyperinsulinemia suppressed endogenous glucose
      production by approximately 8% vs. 30% in NPY- vs. vehicle-infused mice,
      respectively (P < 0.05). Also, VLDL production was significantly higher during
      hyperinsulinemia in NPY- compared with vehicle-infused mice (97.5 +/- 18.0 vs.
      54.7 +/- 14.9 micromol. kg(-1). h(-1); P < 0.01). These data suggest that the
      neurophysiological action of insulin to downregulate hypothalamic NPY release is
      a prerequisite for its ability to suppress hepatic fuel production, whereas it is
      not mandatory for its capacity to modulate glucose disposal or lipolysis.

PMID- 15448081
TI  - Transferrin and iron contribute to the lipolytic effect of serum in isolated
      adipocytes.
AB  - Previous reports have demonstrated that normal serum can increase the rate of
      adipocyte lipolysis in vitro. However, the nature of the lipolytic activity has
      remained obscure. We have investigated the lipolytic activity of human serum
      using isolated rat adipocytes. Human serum resulted in a dose-dependent
      stimulation of lipolysis (glycerol release) in adipocytes, with a half-maximal
      effective dose of 0.05% serum and with maximal stimulation with 1% serum. The
      effect of serum on glycerol release was rapid (within 30 min), and the effect was
      reversible. Partial purification of this lipolytic activity using gel filtration
      and ion-exchange chromatography demonstrates that a protein of approximately 80
      kDa contributes to the lipolytic activity. Human transferrin mimicked the
      activity of partially purified serum, resulting in a maximal 50% increase in
      basal lipolysis. In addition, ferrous sulfate heptahydrate induced a biphasic
      increase in the rate of lipolysis, with a maximal increase of 50% at
      approximately 0.6 microg/ml iron. Inhibitors of protein kinase A (H89) and
      mitogen-activated protein kinase (PD98059) did not block the effect of serum on
      lipolysis, whereas the free radical scavenger N-acetyl-l-cysteine completely
      inhibited the effect. These findings suggest that the stimulatory effect of serum
      on lipolysis is in part mediated by iron, probably through a prooxidant
      mechanism.

PMID- 15448082
TI  - Hypothalamic ATP-sensitive K + channels play a key role in sensing hypoglycemia
      and triggering counterregulatory epinephrine and glucagon responses.
AB  - It has been postulated that specialized glucose-sensing neurons in the
      ventromedial hypothalamus (VMH) are able to detect falling blood glucose and
      trigger the release of counterregulatory hormones during hypoglycemia. The
      molecular mechanisms used by glucose-sensing neurons are uncertain but may
      involve cell surface ATP-sensitive K(+) channels (K(ATP) channels) analogous to
      those of the pancreatic beta-cell. We examined whether the delivery of
      sulfonylureas directly into the brain to close K(ATP) channels would modulate
      counterregulatory hormone responses to either brain glucopenia (using
      intracerebroventricular 5-thioglucose) or systemic hypoglycemia in awake
      chronically catheterized rats. The closure of brain K(ATP) channels by global
      intracerebroventricular perfusion of sulfonylurea (120 ng/min glibenclamide or
      2.7 microg/min tolbutamide) suppressed counterregulatory (epinephrine and
      glucagon) responses to brain glucopenia and/or systemic hypoglycemia (2.8 mmol/l
      glucose clamp). Local VMH microinjection of a small dose of glibenclamide (0.1%
      of the intracerebroventricular dose) also suppressed hormonal responses to
      systemic hypoglycemia. We conclude that hypothalamic K(ATP) channel activity
      plays an important role in modulating the hormonal counterregulatory responses
      triggered by decreases in blood glucose. Our data suggest that closing of K(ATP)
      channels in the VMH (much like the beta-cell) impairs defense mechanisms against
      glucose deprivation and therefore could contribute to defects in glucose
      counterregulation.

PMID- 15448083
TI  - Regulation of growth hormone secretagogue receptor gene expression in the arcuate
      nuclei of the rat by leptin and ghrelin.
AB  - The anorexigenic and orexigenic hormones leptin and ghrelin act in opposition to
      one another. When leptin signaling is reduced, as in the Zucker fatty rat, or
      when circulating ghrelin is increased during fasting, the effect of ghrelin
      becomes more dominant, indicating an influence of both hormones on ghrelin
      action. This effect could be mediated via the level of expression of ghrelin
      receptor (growth hormone secretagogue receptor [GHS-R]). For testing this, GHS-R
      expression was measured using in situ hybridization in Zucker fatty versus lean
      rats; in fed versus fasted (48 h) rats, treated with either ghrelin or leptin;
      and in GH-deficient, dwarf versus control rats. In the arcuate nuclei of the
      Zucker fatty rat and in fasted rats, GHS-R expression is significantly increased.
      A single leptin intracerebroventricular injection attenuated the fasting-induced
      increase in GHS-R but had no effect in fed rats 2 h after injection, whereas
      leptin infusion for 24 h or longer significantly decreased GHS-R expression in
      fed rats. Ghrelin significantly increased GHS-R expression but not in dwarf rats.
      These results show that the level of GHS-R expression in the ARC is reduced by
      leptin and increased by ghrelin and that the effect of ghrelin may be GH
      dependent.

PMID- 15448084
TI  - Response of human islets to isolation stress and the effect of antioxidant
      treatment.
AB  - The process of human islet isolation triggers a cascade of stressful events in
      the islets of Langerhans involving activation of apoptosis and necrosis and the
      production of proinflammatory molecules that negatively influence islet yield and
      function and may produce detrimental effects after islet transplantation. In this
      study, we showed that activation of nuclear factor-kappaB (NF-kappaB) and
      poly(ADP-ribose) polymerase (PARP), two of the major pathways responsible for
      cellular responses to stress, already occurs in pancreatic cells during the
      isolation procedure. NF-kappaB-dependent reactions, such as production and
      release of interleukin-6 and -8 and macrophage chemoattractant protein 1, were
      observed days after the isolation procedure in isolated purified islets. Under
      culture conditions specially designed to mimic isolation stress, islet
      proinflammatory responses were even more pronounced and correlated with higher
      islet cell loss and impaired secretory function. Here we present novel evidence
      that early interventions aimed at reducing oxidative stress of pancreatic cells
      and islets through the use of the catalytic antioxidant probe AEOL10150
      (manganese [III] 5,10,15,20-tetrakis [1,3,-diethyl-2imidazoyl] manganese
      porphyrin pentachloride [TDE-2,5-IP]) effectively reduces NF-kappaB binding to
      DNA, the release of cytokines and chemokines, and PARP activation in islet cells,
      resulting in higher survival and better insulin release. These findings support
      the concept that the isolation process predisposes islets to subsequent damage
      and functional impairment. Blocking oxidative stress can be beneficial in
      reducing islet vulnerability and can potentially have a significant impact on
      transplantation outcome.

PMID- 15448085
TI  - Elevated C-reactive protein levels in the development of type 1 diabetes.
AB  - Elevated C-reactive protein (CRP) levels have previously been described before
      the onset of type 2 diabetes and gestational diabetes. We hypothesized that
      inflammation, as reflected by elevated CRP levels, can help predict development
      of islet autoimmunity or type 1 diabetes. Children at risk for type 1 diabetes
      and followed in the Diabetes Autoimmunity Study of the Young (DAISY) had blood
      samples drawn and frozen serum saved at various intervals after birth. CRP was
      measured using a high-sensitivity sandwich enzyme immunoassay. Islet
      autoantibodies (IAs) were measured using biochemical immunoassays. Elevations in
      CRP concentrations were significantly more frequent (P < 0.01) in children who
      later developed type 1 diabetes (8 of 16 children) than in children negative for
      IAs at their last testing (3 of 26). Children with one or more positive IA were
      more likely to have elevated CRP concentrations (15 of 36) than IA-negative
      children (3 of 26; P < 0.01). The finding of elevated CRP levels in infants and
      young children before the onset of type 1 diabetes adds to the evidence that the
      disease is an immunoinflammatory disorder. The elevated CRP levels may provide an
      additional marker for risk of progression to type 1 diabetes.

PMID- 15448086
TI  - A salen-manganese catalytic free radical scavenger inhibits type 1 diabetes and
      islet allograft rejection.
AB  - Reactive oxygen species, such as superoxide, and nitrogen oxides, such as
      peroxynitrite, are thought to contribute to beta-cell destruction during the
      disease process that leads to type 1 diabetes. EUK-8 is a member of a new class
      of synthetic salen-manganese compounds with low toxicity that possess catalytic
      superoxide dismutase, peroxidase, and catalase activity that can inactivate
      superoxide and nitrogen oxides (e.g., peroxynitrite and nitrogen dioxide). We
      observed that EUK-8 administration inhibited the adoptive transfer of type 1
      diabetes to NOD mice. In addition, administration of EUK-8 to NOD mice with
      established autoimmunity completely prevented the development of type 1 diabetes
      for up to 1 year in age, even though the treatment was discontinued after 35
      weeks of age. EUK-8 treatment also prolonged the survival of islet allografts in
      newly diabetic NOD mice. Thus, reactive oxygen and nitrogen species contribute to
      the pathoetiology of both spontaneous type 1 diabetes and allograft rejection. In
      cultures of NIT-1 cells, EUK-8 inhibited cytotoxicity caused by superoxide as
      well as nitric oxide. Collectively, our findings implicate a greater role for
      nitrogen oxides (other than peroxynitrite) in beta-cell damage. Antioxidants
      designed to prevent the formation of both cytotoxic reactive oxygen and nitrogen
      species may effectively protect beta-cells from spontaneous autoimmunity and
      alloresponses.

PMID- 15448087
TI  - Investigation of the role of B-cells in type 1 diabetes in the NOD mouse.
AB  - B-cells are important in the development of type 1 diabetes, but their role is
      not completely defined. Although B-cells produce autoantibodies, these are not
      thought to be pathogenic; however, their antigen-presenting function is
      postulated to be critical. To examine the relative importance of these functions
      of B-cells, we have generated nonobese diabetic (NOD) B-cell-deficient mice that
      express a transgene encoding a mutant heavy chain immunoglobulin transgene on the
      cell surface but cannot secrete immunoglobulins (mIgs). This allowed us to
      dissect the importance of the relative roles of antigen presentation, dissociated
      from antibody production. We found that the expression of the mIg transgene
      increased insulitis and the incidence of diabetes compared with transgene
      negative NOD B-cell-deficient mice, indicating that the ability to produce
      antibodies is not necessary for B-cells to have some effect on the development of
      diabetes. However, diabetes was not restored to the level seen in normal NOD
      mice. This may relate to reduced ability to activate an islet-specific T-cell
      repertoire, presumably due to the reduced islet-specific B-cell repertoire. Our
      results implicate a specific antigen-presenting function for B-cells.

PMID- 15448088
TI  - Local activation of dendritic cells leads to insulitis and development of insulin
      dependent diabetes in transgenic mice expressing CD154 on the pancreatic beta
      cells.
AB  - The initial events leading to activation of the immune system in type 1 diabetes
      are still largely unknown. In vivo, dendritic cells (DCs) are thought to be the
      only antigen-presenting cells (APCs) capable of activating naive T-cells and are
      therefore important for the initiation of the autoimmune response. To test the
      effect of activating islet-associated APCs in situ, we generated transgenic mice
      expressing CD154 (CD40 ligand) under control of the rat insulin promoter (RIP).
      RIP-CD154 mice developed both insulitis and diabetes, although with different
      incidence in independent lines. We show that activated DCs could be detected both
      in the pancreas and in the draining pancreatic lymph nodes. Furthermore, diabetes
      development was dependent on the presence of T- and B-cells since recombination
      activating gene (RAG)-deficient RIP-CD154 mice did not develop diabetes. Finally,
      we show that the activation of immune cells was confined to the pancreas because
      transplantation of nontransgenic islets to diabetic recipients restored
      normoglycemia. Together, these data suggest that expression of CD154 on the beta
      cells can lead to activation of islet-associated APCs that will travel to the
      lymph nodes and activate the immune system, leading to insulitis and diabetes.

PMID- 15448089
TI  - Promotion of beta-cell differentiation by conophylline in fetal and neonatal rat
      pancreas.
AB  - Conophylline is a vinca alkaloid extracted from the tropical plant Ervatamia
      microphylla and has been shown to induce differentiation of pancreatic AR42J
      cells. In the present study, we investigated the effect of conophylline on the
      differentiation of pancreatic precursor cells. In the rat pancreatic rudiment in
      organ culture, conophylline inhibited the formation of cystic structure and
      increased the number of insulin-positive cells. Conophylline also markedly
      increased the expression of mRNA for insulin and the number of pancreatic
      duodenal homeobox-1-positive cells. These effects of conophylline were similar to
      those of activin A. We also examined the effect of conophylline on neonatal rats
      treated with streptozotocin, a model of type 2 diabetes. Treatment with
      conophylline significantly reduced the plasma glucose concentration and improved
      glucose tolerance in response to glucose loading. The insulin content and the
      beta-cell mass at 2 months were significantly increased by conophylline. The
      number of islet-like cell clusters and pancreatic duodenal homeobox-1-positive
      ductal cells was greater in conophylline-treated rats. These results suggest that
      conophylline induces differentiation of pancreatic precursor cells and increases
      the formation of beta-cells.

PMID- 15448090
TI  - Artifactual insulin release from differentiated embryonic stem cells.
AB  - Several recent reports claim the generation of insulin-producing cells from
      embryonic stem cells via the differentiation of progenitors that express nestin.
      Here, we investigate further the properties of these insulin-containing cells. We
      find that although differentiated cells contain immunoreactive insulin, they do
      not contain proinsulin-derived C-peptide. Furthermore, we find variable insulin
      release from these cells upon glucose addition, but C-peptide release is never
      detected. In addition, many of the insulin-immunoreactive cells are undergoing
      apoptosis or necrosis. We further show that cells cultured in the presence of a
      phosphoinositide 3-kinase inhibitor, which previously was reported to facilitate
      the differentiation of insulin(+) cells, are not C-peptide immunoreactive but
      take up fluorescein isothiocyanate-labeled insulin from the culture medium.
      Together, these data suggest that nestin(+) progenitor cells give rise to a
      population of cells that contain insulin, not as a result of biosynthesis but
      from the uptake of exogenous insulin. We conclude that C-peptide biosynthesis and
      secretion should be demonstrated to claim insulin production from embryonic stem
      cell progeny.

PMID- 15448091
TI  - Evidence against the involvement of oxidative stress in fatty acid inhibition of
      insulin secretion.
AB  - Prolonged exposure to elevated levels of fatty acids adversely affects pancreatic
      beta-cell function. Here we investigated 1) whether ceramide synthesis, which we
      reported to mediate fatty acid inhibition of insulin gene expression, also
      inhibits insulin secretion and 2) whether fatty acid inhibition of insulin
      secretion involves the generation of reactive oxygen species (ROS), nitric oxide
      (NO), or prostaglandin E(2) (PGE(2)). A 72-h culture of islets in the presence of
      palmitate or oleate resulted in a marked decrease in glucose-induced insulin
      release assessed in 1-h static incubations. This effect was reproduced by
      exogenous diacylglycerol, but not by a cell-permeable analog of ceramide. Culture
      in the presence of fatty acids was not associated with an increase in
      intracellular peroxide or NO levels, neither was insulin secretion restored by
      antioxidants or an inhibitor of NO production. Exposure to fatty acids led to an
      increase in PGE(2) release, but an inhibitor of cyclooxygenase 2 was unable to
      prevent fatty acid inhibition of insulin secretion. These results indicate that
      fatty acid inhibition of insulin secretion 1) is not mediated by de novo ceramide
      synthesis, ROS, NO, or PGE(2), and 2) is likely to be caused by the generation of
      signals or metabolites downstream of diacylglycerol.

PMID- 15448092
TI  - Hepatic insulin resistance precedes the development of diabetes in a model of
      intrauterine growth retardation.
AB  - Intrauterine growth retardation (IUGR) has been linked to the development of type
      2 diabetes in adulthood. We developed an IUGR model in rats whereby at age 3-6
      months the animals develop a diabetes that is associated with insulin resistance.
      Hyperinsulinemic-euglycemic clamp studies were performed at age 8 weeks, before
      the onset of obesity and diabetes. Basal hepatic glucose production (HGP) was
      significantly higher in IUGR than in control rats (14.6 +/- 0.4 vs. 12.3 +/- 0.3
      mg. kg(-1). min(-1); P < 0.05). Insulin suppression of HGP was blunted in IUGR
      versus control rats (10.4 +/- 0.6 vs. 6.5 +/- 1.0 mg. kg(-1). min(-1); P < 0.01);
      however, rates of glucose uptake and glycogenolysis were similar between the two
      groups. Insulin-stimulated insulin receptor substrate 2 and Akt-2 phosphorylation
      were significantly blunted in IUGR rats. PEPCK and glucose-6-phosphatase mRNA
      levels were increased at least threefold in liver of IUGR compared with control
      rats. These studies suggest that an aberrant intrauterine milieu permanently
      impairs insulin signaling in the liver so that gluconeogenesis is augmented in
      the IUGR rat. These processes occur early in life, before the onset of
      hyperglycemia, and indicate that uteroplacental insufficiency causes a primary
      defect in gene expression and hepatic metabolism that leads to the eventual
      development of overt hyperglycemia.

PMID- 15448093
TI  - Elevations in markers of liver injury and risk of type 2 diabetes: the insulin
      resistance atherosclerosis study.
AB  - A limited number of studies have reported associations of markers of liver
      injury, including elevated concentrations of aspartate aminotransferase (AST) and
      alanine aminotransferase (ALT), with prospective risk of type 2 diabetes.
      However, only one study has adjusted for a detailed measure of insulin
      sensitivity (insulin sensitivity index [S(i)]), which is important given
      associations of obesity and S(i) with nonalcoholic fatty liver disease (NAFLD).
      Our objective was to investigate the associations of elevated AST and ALT with
      incident type 2 diabetes among 906 participants in the Insulin Resistance
      Atherosclerosis Study who were nondiabetic at baseline. S(i) and acute insulin
      response (AIR) were measured directly from the frequently sampled intravenous
      glucose tolerance test among black, Hispanic, and non-Hispanic white participants
      aged 40-69 years. After 5.2 years, 148 individuals had developed type 2 diabetes.
      Baseline AST and ALT were positively correlated with fasting insulin (r = 0.22
      and r = 0.35, respectively), waist circumference (r = 0.18 and r = 0.34), and
      fasting glucose (r = 0.13 and r = 0.29) and inversely with S(i) (r = -0.18 and r
      = -0.30; all P < 0.0001). In separate logistic regression models adjusting for
      age, sex, ethnicity, clinical center, and alcohol consumption, participants in
      the highest quartiles (Q4) of AST and ALT were at significantly increased risk of
      incident type 2 diabetes compared with those in the lowest three quartiles (Q1
      Q3): AST: odds ratio (OR) 1.73 (95% CI 1.17-2.57); ALT: OR 2.32 (1.36-3.75).
      After further adjustment for smoking, waist circumference, triglyceride, HDL,
      impaired glucose tolerance, S(i), and AIR, both AST and ALT remained
      significantly associated with incident type 2 diabetes: AST, Q4 vs. Q1-Q3: OR
      1.98 (1.23-3.17); ALT, Q4 vs. Q1-Q3: OR 2.00 (1.22-3.28). There were no
      interactions of sex, ethnicity, obesity, impaired glucose tolerance, or S(i) with
      AST or ALT in the prediction of type 2 diabetes. When entered into the same model
      with adjustment for demographic variables, both C-reactive protein and ALT
      independently predicted type 2 diabetes. In addition, AST and ALT were positively
      associated with incident type 2 diabetes after excluding former and moderate to
      heavy drinkers. In conclusion, AST and ALT independently predict type 2 diabetes.
      Baseline elevations of these markers may reflect NAFLD or related pathologies.

PMID- 15448094
TI  - Alterations in plasma vitamin E distribution in type 2 diabetic patients with
      elevated plasma phospholipid transfer protein activity.
AB  - Mouse studies indicated that plasma phospholipid transfer protein (PLTP)
      determines the plasma distribution of vitamin E, a potent lipophilic antioxidant.
      Vitamin E distribution, antioxidant status, and titer of anti-oxidized LDLs
      (oxLDL) autoantibodies were evaluated in plasma from control subjects (n = 31)
      and type 2 diabetic patients (n = 31) with elevated plasma PLTP concentration.
      Unlike diabetic and control HDLs, which displayed similar vitamin E contents,
      diabetic VLDLs and diabetic LDLs contained fewer vitamin E molecules than normal
      counterparts. Plasma PLTP concentration in diabetic plasmas correlated negatively
      with vitamin E in VLDL+LDL, but positively with vitamin E in HDL, with an even
      stronger correlation with the VLDL+LDL-to-HDL vitamin E ratio. Circulating levels
      of oxLDL were significantly higher in diabetic plasmas than in control plasmas.
      Whereas the titer of IgG autoantibodies to modified LDL did not differ
      significantly between diabetic patients and control subjects, diabetic plasmas
      showed significantly lower levels of potentially protective IgM autoantibodies.
      The present observations support a pathophysiological role of PLTP in decreasing
      the vitamin E content of apolipoprotein B-containing lipoproteins, but not of HDL
      in plasma of type 2 diabetic patients, contributing to a greater potential for
      LDL oxidation.

PMID- 15448095
TI  - Nitric oxide-sensitive soluble guanylyl cyclase activity is preserved in internal
      mammary artery of type 2 diabetic patients.
AB  - Vascular reactivity to nitric oxide (NO) is mediated by NO-sensitive soluble
      guanylyl cyclase (sGC). Since a diminished activity of vascular sGC has been
      reported in an animal model of type 2 diabetes, the sGC activity was assayed in
      vitro in internal mammary artery specimens obtained during bypass surgery from
      patients with and without type 2 diabetes. The sensitivity of sGC to NO, which is
      dependent on Fe(2+)-containing heme, was measured in vitro using stimulation with
      diethylamine NONOate (DEA/NO). In addition, the novel cyclic guanosine
      monophosphate-elevating compound HMR-1766 was used to test the stimulation of the
      oxidized heme-Fe(3+)-containing form of sGC. Basal activity of sGC and its
      sensitivity to stimulation by DEA/NO and HMR-1766 were not different between
      control and type 2 diabetic patients: maximum stimulation by DEA/NO amounted to
      475 +/- 67 and 418 +/- 59 pmol. mg(-1). min(-1) in control and type 2 diabetic
      patients, respectively. The maximum effects of HMR-1766 were 95 +/- 18 (control
      subjects) and 83 +/- 11 pmol. mg(-1). min(-1) (type 2 diabetic patients).
      Hypertension, hyperlipidemia, drug treatment with statins, ACE inhibitors, or
      nitrates had no effect on sGC activity. In conclusion, the present findings do
      not support the hypothesis that desensitization of sGC contributes to the
      pathogenesis of diabetic vascular dysfunction in humans.

PMID- 15448096
TI  - Preserved glucoregulation but attenuation of the vascular actions of insulin in
      mice heterozygous for knockout of the insulin receptor.
AB  - Type 2 diabetes is preceded by years of insulin resistance and is characterized
      by reduced bioavailability of the antiatherosclerotic signaling molecule nitric
      oxide (NO) and premature atherosclerosis. The relationship between resistance to
      the glucoregulatory actions of insulin and its effects on the vasculature (in
      particular NO-dependent responses) is poorly characterized. We studied this
      relationship in mice heterozygous for knockout of the insulin receptor (IRKO),
      which have a mild perturbation of insulin signaling. Male heterozygous IRKO mice
      aged 8-12 weeks were compared with age- and sex-matched littermates. IRKO mice
      had fasting blood glucose, insulin, free fatty acid, and triglyceride levels
      similar to those of wild-type mice. Intraperitoneal glucose and insulin tolerance
      tests were also similar in the two groups. Insulin levels in response to a
      glucose load were approximately twofold higher in IRKO compared with wild-type
      mice (1.08 +/- 0.11 vs. 0.62 +/- 0.13 ng/ml; P = 0.004). Despite this mild
      metabolic phenotype, IRKO mice had increased systolic blood pressure (124 +/- 4
      vs. 110 +/- 3 mmHg; P = 0.01). Basal NO bioactivity, assessed from the increase
      in tension of phenylephrine preconstricted aortic rings in response to the NO
      synthase inhibitor N(G)-monomethyl-l-arginine, was reduced in IRKO (61 +/- 14 vs.
      152 +/- 30%; P = 0.005). Insulin-mediated NO release in aorta, assessed as the
      reduction in phenylephrine constrictor response after insulin preincubation, was
      lost in IRKO mice (5 +/- 8% change vs. 66 +/- 9% reduction in wild-type; P =
      0.03). Insulin-stimulated aortic endothelial NO synthase phosphorylation was also
      significantly blunted in IRKO mice (P < 0.05). These data demonstrate that
      insulin-stimulated NO responses in the vasculature are exquisitely sensitive to
      changes in insulin-signaling pathways in contrast to the glucoregulatory actions
      of insulin. These findings underscore the importance of early intervention in
      insulin-resistant states, where glucose homeostasis may be normal but substantial
      abnormalities of the vascular effects of insulin may already be present.

PMID- 15448097
TI  - Glycation inactivation of the complement regulatory protein CD59: a possible role
      in the pathogenesis of the vascular complications of human diabetes.
AB  - Micro- and macrovascular diseases are major causes of morbidity and mortality in
      the diabetic population, but the cellular and molecular mechanisms that link
      hyperglycemia to these complications remain incompletely understood. We proposed
      that in human diabetes, inhibition by glycation of the complement regulatory
      protein CD59 increases deposition of the membrane attack complex (MAC) of
      complement, contributing to the higher vascular risk. We report here 1) the
      generation and characterization of an anti-glycated human CD59 (hCD59) specific
      antibody, 2) the detection with this antibody of glycated hCD59 colocalized with
      MAC in kidneys and nerves from diabetic but not from nondiabetic subjects, and 3)
      a significantly reduced activity of hCD59 in erythrocytes from diabetic subjects,
      a finding consistent with glycation inactivation of hCD59 in vivo. Because hCD59
      acts as a specific inhibitor of MAC formation, these findings provide a molecular
      explanation for the increased MAC deposition reportedly found in the target
      organs of diabetic complications. We conclude that glycation inactivation of
      hCD59 that leads to increased MAC deposition may contribute to the extensive
      vascular pathology that complicates human diabetes.

PMID- 15448098
TI  - Thiazolidinediones reduce endothelial expression of receptors for advanced
      glycation end products.
AB  - Advanced glycation end products (AGEs) are critically involved in atherogenesis
      in diabetes by binding to receptors for AGE (RAGEs) in vascular cells, thus
      inducing the expression of proinflammatory mediators. In animal models,
      interruption of the AGE-RAGE interaction reduces lesion size and plaque
      development. Therefore, limiting RAGE expression might be an intriguing concept
      to modulate vascular disease in diabetic patients. The present study investigated
      whether thiazolidinediones (TZDs), antidiabetic agents clinically used to treat
      patients with type 2 diabetes, might modulate endothelial RAGE expression.
      Stimulation of human endothelial cells with rosiglitazone or pioglitazone
      decreased basal as well as tumor necrosis factor-alpha-induced RAGE cell surface
      and total protein expression. In addition, TZDs reduced RAGE mRNA expression in
      endothelial cells. These effects on RAGE expression were caused by an inhibition
      of nuclear factor-kappaB (NF-kappaB) activation at the proximal NF-kappaB site of
      the RAGE promoter. The functional relevance of reduced RAGE expression was
      demonstrated by showing that pretreatment of endothelial cells with TZDs
      decreased AGE- as well as beta-amyloid-induced monocyte chemoattractant protein-1
      expression. In conclusion, TZDs reduce RAGE expression in human endothelial
      cells, thus limiting the cells' susceptibility toward proinflammatory AGE
      effects. These data provide new insight on how TZDs, in addition to their
      metabolic effects, might modulate the development of vascular dysfunction in
      diabetic patients.

PMID- 15448099
TI  - Selective loss of calcitonin gene-related Peptide-expressing primary sensory
      neurons of the a-cell phenotype in early experimental diabetes.
AB  - To evaluate the possible role of neuropeptide immunoreactive primary sensory
      neurons on the development of nociceptive dysfunction in diabetes, the absolute
      numbers of immunoreactive substance P and calcitonin gene-related peptide (CGRP)
      dorsal root ganglion (DRG) cell bodies were estimated in diabetic and nondiabetic
      BALB/C (p75(+/+)) and p75 receptor knockout (p75(-/-)) mice with unilateral
      sciatic nerve crush. The total numbers of immunoreactive substance P A-cells,
      substance P B-cells, CGRP A-cells, and CGRP B-cells in L5DRG were estimated using
      semithick consecutive sections and the optical fractionator. After 4 weeks of
      streptozotocin-induced diabetes, the number of immunoreactive CGRP A-cells was
      reduced from 692 +/- 122 to 489 +/- 125 (P = 0.004) in p75(+/+) mice on the
      noncrushed side. In p75(-/-) mice, there was no such effect of diabetes on the
      immunoreactive CGRP A-cell number. In p75(+/+) and p75(-/-) mice, there was no
      effect of diabetes on the immunoreactive CGRP B-cell number, nor was there any
      effect of diabetes on the immunoreactive substance P B-cell number. Sciatic nerve
      crush was associated with a substantial loss of L5DRG B-cells in diabetic and
      nondiabetic p75(+/+) mice and with substantial loss of immunoreactive substance P
      cells in diabetic p75(+/+) mice. In diabetic and nondiabetic p75(-/-) mice, there
      was no crush effect on neuropeptide expression. It is concluded that experimental
      diabetes in the mouse is associated with loss of immunoreactive CGRP primary
      sensory neurons of the A-cell phenotype, that this loss could play a role for the
      touch-evoked nociception in the model, and that the neuronal immunoreactive CGRP
      abnormality possibly is mediated by activation of the p75 neurotrophin receptor.

PMID- 15448100
TI  - Genome-wide scan for metabolic syndrome and related quantitative traits in Hong
      Kong Chinese and confirmation of a susceptibility locus on chromosome 1q21-q25.
AB  - We conducted autosomal genome scans to map loci for metabolic syndrome (MES) and
      related traits in the Hong Kong Family Diabetes Study. We selected 55 families
      with 137 affected members (121 affected relative pairs) for nonparametric linkage
      analysis on MES. We also selected 179 families with 897 members (2,127 relative
      pairs) for variance component-based linkage analyses on seven MES-related traits:
      waist circumference, systolic and diastolic blood pressure (BP), triglyceride,
      HDL cholesterol, fasting plasma glucose, and insulin resistance index (insulin
      resistance index by homeostasis model assessment [HOMA%IR]). Analyses revealed
      three regions that showed suggestive linkage for MES and also showed overlapping
      signals for metabolic traits: chromosome 1 at 169.5-181.5 cM (logarithm of odds
      [LOD] = 4.50 for MES, 3.71 for waist circumference, and 1.24 for diastolic BP),
      chromosome 2 at 44.1-57.3 cM (LOD = 2.22 for MES, 2.07 for fasting plasma
      glucose, and 1.29 for diastolic BP), and chromosome 16 at 45.2-65.4 cM (LOD =
      1.75 for MES, 1.61 for HOMA%IR, and 1.25 for HDL cholesterol). Other regions that
      showed suggestive linkages included chromosome 5q for diastolic BP; 2q, 3q, 6q,
      9q, 10q, and 17q for triglyceride; 12p, 12q, and 22q for HDL-C; and 6q for
      HOMA%IR. Simulation studies demonstrated genome-wide significant linkage of the
      chromosome 1 region to both MES and waist circumference (P(genome-wide) = 0.002
      and 0.019, respectively). In summary, we have found a susceptibility locus on
      chromosome 1q21-q25 involved in the pathogenesis of multiple metabolic
      abnormalities, in particular obesity. Our results confirm the findings of
      previous studies on diabetes and related phenotypes. We also suggest the
      locations of other loci that may contribute to the development of MES in Hong
      Kong Chinese.

PMID- 15448101
TI  - Differences in the contribution of HLA-DR and -DQ haplotypes to susceptibility to
      adult- and childhood-onset type 1 diabetes in Japanese patients.
AB  - To clarify heterogeneity in Japanese adult-onset type 1 diabetes, we analyzed the
      HLA-DR and -DQ haplotypes, depending on the clinical phenotype, and compared them
      with those in childhood-onset type 1 diabetes (CO). The patients in a previously
      reported Ehime Study were divided into subgroups by the mode of onset of
      diabetes: 68 acute-onset type 1 diabetic patients (AO) and 28 slowly progressive
      type 1 diabetic patients (SO). HLA haplotypes were compared with those of 80 CO
      patients and 190 control subjects. Two major susceptible HLA haplotypes in the
      Japanese, DRB1*0405-DQB1*0401 (DR4) and DRB1*0901-DQB1*0303 (DR9), were
      significantly increased in the AO and CO groups, but only DR9 was increased in
      the SO group. AO subjects had a higher frequency of DR9 than CO subjects.
      Accordingly, the DR9:DR4 frequency increased with increasing age of onset.
      Another susceptible haplotype, DRB1*0802-DQB1*0302 (DR8), was involved only in
      the CO group. Analysis of haplotype combinations revealed that DR4 and DR9 had
      significant dosage effects on the AO and CO groups (P < 0.0001), but only DR9 had
      such an effect in the SO group (P < 0.03). These results suggest differences in
      the contribution of HLA class II haplotypes to susceptibility of type 1 diabetes
      depending on the clinical phenotype and also indicate that HLA class II
      haplotypes may be associated with the onset age of type 1 diabetes.

PMID- 15448102
TI  - Intercellular adhesion molecule-1 concentration is genetically correlated with
      insulin resistance, obesity, and HDL concentration in Mexican Americans.
AB  - The metabolic syndrome and type 2 diabetes are associated with endothelial
      activation (and thus with inflammatory processes leading to atherosclerosis), but
      the mechanisms that underlie these associations are not fully understood.
      Endothelial intercellular adhesion molecule (ICAM)-1 plays an important role in
      the recruitment of immune cells during the development of atherosclerotic plaque
      and is a marker of inflammatory disease. We performed bivariate quantitative
      genetic analyses to estimate genetic and environmental correlations between
      circulating ICAM-1 concentration and 17 phenotypes associated with the metabolic
      syndrome. Our study population comprised 428 adults in 20 extended Mexican
      American families from the San Antonio Family Heart Study (SAFHS). Circulating
      ICAM-1 concentration is heritable (h(2) = 0.56). ICAM-1 concentration showed
      significant positive genetic correlations (range 0.32-0.52, P < 0.05) with
      fasting insulin, insulin 2 h after oral glucose challenge, homeostasis model
      assessment of insulin resistance, BMI, waist circumference, and leptin
      concentration; negative genetic correlation with HDL3 cholesterol concentration;
      and negative environmental correlation with adiponectin concentration.
      Significant genetic correlations were not found between ICAM-1 and fasting or 2-h
      serum glucose or systolic or diastolic blood pressure. Thus, ICAM-1 expression
      may share common genetic modulation with traits related to obesity, insulin
      resistance, and HDL3 cholesterol, but not with hyperglycemia or hypertension per
      se.

PMID- 15448103
TI  - Melanocortin 4 receptor gene variation is associated with severe obesity in Pima
      Indians.
AB  - Heterozygous coding mutations in the melanocortin 4 receptor gene (MC4R) are the
      most common genetic causes of severe human obesity identified to date. To
      determine whether MC4R has a role in causing severe obesity in Pima Indians, we
      sequenced the coding region of this gene in 426 full-heritage, non-first-degree
      related, adult Pima Indians (300 severely obese and 126 nondiabetic nonobese
      control subjects). Three coding variations were detected as heterozygotes only in
      severely obese subjects. One variation, detected in three obese subjects, was a
      novel single-base insertion (A) at nucleotide 100, and it predicted a frameshift
      and premature STOP at codon 37. The second variant, detected in 10 obese
      subjects, predicted a previously identified arginine-to-glutamine substitution at
      codon 165, and the third variant, detected in one obese subject, predicted a
      novel glycine-to-serine substitution at codon 231. Three polymorphisms were also
      identified in the 5' untranslated region, but these variants were detected in
      both obese and lean subjects and had similar allele frequencies. We conclude that
      variations in MC4R may account for a small portion of obesity in Pima Indians,
      but they do not explain the overall high prevalence of obesity in this Native
      American population.

PMID- 15448104
TI  - Genetic evidence for discordance between obesity- and diabetes-related traits in
      the LGXSM recombinant inbred mouse strains.
AB  - Obesity and its comorbidities, particularly type 2 diabetes, have become serious
      public health problems over the past few decades. Although the current pandemic
      is largely caused by societal environmental changes in diet, variation in
      response to these changes have, in part, a genetic basis. Here we address the
      genetic basis for both obesity- and diabetes-related traits themselves and
      dietary fat responses for these traits in a set of recombinant inbred mouse
      strains formed from the cross of LG/J with SM/J (LGXSM lines) fed a standard low
      fat (15% calories from fat) or high-fat (42% calories from fat) diet. We found
      substantial genetic variation for most of the traits studied. Weight at time of
      death, liver weight, and weight of the reproductive fat pad had especially high
      heritabilities, whereas heart weight and serum levels of free fatty acids and
      triglycerides had low heritabilities. Genetic correlations were very high among
      fat pad weights and serum leptin, indicating shared genetic variation between fat
      levels and hormonal appetite control. These obesity traits were moderately
      correlated with adult growth, liver weight, and serum insulin and cholesterol
      levels. A majority of traits also displayed genetic variation in response to a
      high-fat diet, especially the weight of the reproductive and renal fat pads as
      well as the liver. Genetic correlations in dietary response followed a pattern
      similar to that found for the traits themselves. Several strains manifested
      discordant responses for obesity, glucose, and insulin, consistent with the
      presence of genotypes protective for diabetes in the presence of obesity. These
      recombinant inbred strains represent potentially valuable new models for
      dissecting the complex physiological relationships among obesity and diabetes.

PMID- 15448105
TI  - Analysis of the vitamin D receptor gene sequence variants in type 1 diabetes.
AB  - Vitamin D is known to modulate the immune system, and its administration has been
      associated with reduced risk of type 1 diabetes. Vitamin D acts via its receptor
      (VDR). Four single nucleotide polymorphisms (SNPs) of the VDR gene have been
      commonly studied, and evidence of association with type 1 diabetes has been
      reported previously. We sequenced the VDR gene region and developed its SNP map.
      Here we analyzed association of the 98 VDR SNPs in up to 3,763 type 1 diabetic
      families. First, we genotyped all 98 SNPs in a minimum of 458 U.K. families with
      two affected offspring. We further tested eight SNPs, including four SNPs
      associated with P < 0.05 in the first set and the four commonly studied SNPs, in
      up to 3,305 additional families from the U.K., Finland, Norway, Romania, and U.S.
      We only found weak evidence of association (P = 0.02-0.05) of the rs4303288,
      rs12721366, and rs2544043 SNPs. We then tested these three SNPs in an independent
      set of 1,587 patients and 1,827 control subjects from the U.K. and found no
      evidence of association. Overall, our results indicate that common sequence
      variation in the VDR gene has no major effect in type 1 diabetes in the
      populations tested.

PMID- 15448106
TI  - Permanent neonatal diabetes due to mutations in KCNJ11 encoding Kir6.2: patient
      characteristics and initial response to sulfonylurea therapy.
AB  - Permanent neonatal diabetes (PND) can be caused by mutations in the transcription
      factors insulin promoter factor (IPF)-1, eukaryotic translation initiation factor
      2alpha kinase 3 (EIF2AK3), and forkhead box-P3 and in key components of insulin
      secretion: glucokinase (GCK) and the ATP-sensitive K(+) channel subunit Kir6.2.
      We sequenced the gene encoding Kir6.2 (KCNJ11) in 11 probands with GCK-negative
      PND. Heterozygous mutations were identified in seven probands, causing three
      novel (F35V, Y330C, and F333I) and two known (V59M and R201H) Kir6.2 amino acid
      substitutions. Only two probands had a family history of diabetes. Subjects with
      the V59M mutation had neurological features including motor delay. Three mutation
      carriers tested had an insulin secretory response to tolbutamide, but not to
      glucose or glucagon. Glibenclamide was introduced in increasing doses to
      investigate whether sulfonylurea could replace insulin. At a glibenclamide dose
      of 0.3-0.4 mg. kg(-1). day(-1), insulin was discontinued. Blood glucose did not
      deteriorate, and HbA(1c) was stable or fell during 2-6 months of follow-up. An
      oral glucose tolerance test performed in one subject revealed that glucose
      stimulated insulin release was restored. Mutations in Kir6.2 were the most
      frequent cause of PND in our cohort. Apparently insulin-dependent patients with
      mutations in Kir6.2 may be managed on an oral sulfonylurea with sustained
      metabolic control rather than insulin injections, illustrating the principle of
      pharmacogenetics applied in diabetes treatment.

PMID- 15448107
TI  - Kir6.2 mutations are a common cause of permanent neonatal diabetes in a large
      cohort of French patients.
AB  - Permanent neonatal diabetes (PND), requiring insulin within the first months of
      life, is unexplained at the molecular level in most cases. It has very recently
      been shown that heterozygous activating mutations in the KCNJ11 gene, encoding
      the Kir6.2 subunit of the pancreatic ATP-sensitive K(+) channel involved in the
      regulation of insulin secretion, cause PND. In the present study, we screened the
      KCNJ11 gene for mutations in French patients with PND. Patients were recruited
      through the French network for the study of neonatal diabetes. Seventeen at-term
      babies with a median age at diagnosis of diabetes of 64 days (range 1-260) were
      included. We identified in nine patients seven heterozygous nonsynonymous
      mutations: three of them (V59M, R201C, and R201H) were already described, and the
      four novel mutations resulted in an amino acid change of Kir6.2 at positions
      F35L, G53N, E322K, and Y330C. More patients with a Kir6.2 mutation (six of nine)
      were reported to have a smaller birth weight than those without mutation (two of
      eight). Although Kir6.2 mutation carriers do not represent a phenotypically
      specific form of PND, an impaired function of Kir6.2 is associated with in utero
      insulin secretory insufficiency and growth retardation. In conclusion, we
      confirmed that Kir6.2 mutations are a common cause (53%) of PND in Caucasians.

PMID- 15448108
TI  - Gene therapy using replication-defective herpes simplex virus vectors expressing
      nerve growth factor in a rat model of diabetic cystopathy.
AB  - Diabetic cystopathy is one of the common complications of diabetes and current
      therapy is limited. In the present study, the effects of gene therapy, using
      replication-defective herpes simplex virus type 1 (HSV-1) vectors to deliver and
      express the nerve growth factor (NGF) gene (HSV-NGF) on tissue NGF levels and
      bladder function, were evaluated in streptozotocin (STZ)-induced diabetic rats.
      Diabetic rats exhibited a significant decrease in NGF levels in the bladder and
      lumbosacral dorsal root ganglia (DRG) detected by enzyme-linked immunosorbent
      assay and displayed marked bladder dysfunction 12 weeks after STZ injection. In
      contrast, rats with bladder wall injection of the NGF expression vector 8 weeks
      after STZ treatment exhibited a significant increase of NGF levels in the bladder
      and L6 DRG 4 weeks after HSV-NGF injection. Along with the restoration of tissue
      NGF expression, in metabolic cage studies and cystometry, HSV-NGF-injected rats
      also showed significantly reduced bladder capacity and postvoid residual volume
      than diabetic rats injected with the control vector (HSV-lacZ), indicating that
      voiding function was improved after HSV vector-mediated NGF gene delivery. Thus,
      HSV vector-mediated NGF gene therapy may prove useful to restore decreased NGF
      expression in the bladder and bladder afferent pathways, thereby improving
      hypoactive bladder function in diabetes.

PMID- 15448109
TI  - Effect of melatonin on the retinal glutamate/glutamine cycle in the golden
      hamster retina.
AB  - Glutamate is the main excitatory neurotransmitter in the retina, but it is
      neurotoxic when present in excessive amounts. The metabolic dependence of
      glutamatergic neurons upon glia via the glutamate/glutamine cycle to provide the
      precursor for neurotransmitter glutamate is well established. Since melatonin has
      been shown to be neuroprotective in several systems, in the present report, its
      effect on the glutamate/glutamine cycle activity was examined in the golden
      hamster retina. Melatonin (0.1-10 nM) significantly increased retinal glutamine
      synthetase activity but it did not affect L-glutamine release. A characterization
      of the hamster retinal L-glutamine uptake mechanism was performed. This mechanism
      was partly Na+-dependent, and it was significantly inhibited by 2-aminobicyclo
      (2, 2, 1) heptane 2-carboxylic acid (BCH, a selective antagonists for the L-type
      system) and by alpha-(methylamino)-isobutyric acid (MeAIB, substrate
      characteristic for the A -type transporter) suggesting the coexistence of these
      transport systems in the hamster retina. Melatonin (0.1-10 nM) significantly
      increased total glutamine uptake as well as the BCH and the MeAIB-insensitive
      transporters activity. On the other hand, melatonin significantly decreased
      retinal glutaminase activity. On the basis of these results, it might be presumed
      that hamster retinal glutamate/glutamine cycle activity is regulated by
      physiological concentrations of melatonin. Furthermore, these findings suggest
      that a treatment with melatonin could be considered as a new approach to handling
      glutamate-mediated neuronal degeneration.

PMID- 15448110
TI  - Physiological levels of amyloid peptides stimulate the angiogenic response
      through FGF-2.
AB  - Amyloid beta peptides (Abeta) form insoluble aggregates in Alzheimer's disease.
      Accumulation of misfolded amyloid fibrils is generally believed to be a key
      pathogenic event in several brain disorders. Here we show that small amounts of
      Abeta peptides activate angiogenesis by promoting endothelial cell proliferation
      and migration as well as pseudocapillary formation. Abeta peptides functionally
      synergize with fibroblast growth factor (FGF-2) to promote c-Raf and ERK1/2
      activation and angiogenesis in vivo. Thus, Abeta peptides at nanomolar
      concentrations prime FGF-2 effects on the endothelium, enhancing survival and
      sustaining angiogenesis. The angiogenesis promoted by Abeta peptides via FGF-2
      might have implications for understanding the initial stages of Alzheimer's
      disease and for the design of therapies targeting beta amyloid.

PMID- 15448111
TI  - Improvement of defective sarcoplasmic reticulum Ca2+ transport in diabetic heart
      of transgenic rats expressing the human kallikrein-1 gene.
AB  - The bradykinin-forming enzyme kallikrein-1 is expressed in the heart. To examine
      whether contractile performance and sarcoplasmic reticulum Ca2+ transport of the
      diabetic heart can be rescued by targeting the kallikrein-kinin system, we
      studied left ventricular function and sarcoplasmic reticular Ca2+ uptake after
      induction of streptozotocin-induced diabetes mellitus in transgenic rats
      expressing the human tissue kallikrein-1 gene. Six weeks after a single injection
      of either streptozotocin (70 mg/kg ip) or vehicle, left ventricular performance
      was determined using a Millar-Tip catheter system. The Ca2+-transporting activity
      of reticulum-derived membrane vesicles was determined in left ventricular
      homogenates as oxalate-supported 45Ca2+ uptake. Western blot analysis was used to
      quantify the reticular Ca2+-ATPase SERCA2a, phospholamban, and the
      phosphorylation status of the latter. Contractile performance and Ca2+ uptake
      activity were similar in nondiabetic wild-type and transgenic rats. Severely
      diabetic wild-type animals exhibited impaired left ventricular performance and
      decreased reticular Ca2+ uptake (-39% vs. wild-type rats, P<0.05, respectively).
      These changes were attenuated in diabetic transgenic rats that, in addition,
      exhibited a markedly increased phospholamban phosphorylation at the
      Ca2+/calmodulin kinase-specific site threonine17 (2.2-fold vs. diabetic wild-type
      rats, P<0.05). These transgene-related effects were abolished after treatment
      with the bradykinin B2 receptor antagonist icatibant (Hoe 140). The SERCA2-to
      phospholamban ratio, phosphoserine16-phospholamban levels, and the apparent
      affinity for Ca2+ of the uptake reaction did not differ between the groups.
      Increasing the activity of the kallikrein-kinin system by expressing a human
      kallikrein-1 transgene protects rat heart against diabetes-induced contractile
      and reticular Ca2+ transport dysfunctions. An increased phosphorylation of the
      SERCA2 regulatory protein phospholamban at threonine17 via a B2 receptor-mediated
      mechanism is thereby involved.

PMID- 15448112
TI  - Pharmacological inhibition of phosphodiesterase 4 triggers ovulation in follicle
      stimulating hormone-primed rats.
AB  - Phosphodiesterases (PDEs) are a family of enzymes that hydrolyze cyclic
      nucleotides to render them biologically inactive. As such, these enzymes are
      critical regulators of signal transduction pathways that use cyclic nucleotides
      as second messengers. PDE4 is one such member that has been identified in ovarian
      tissue and purported to have a role in the regulation of gonadotropin action. In
      the present study, selective PDE4 inhibitors enhanced intracellular signaling in
      a human LH receptor-expressing granulosa cell line. In vivo, PDE4 inhibition in
      FSH-primed rats resulted in ovulation, indicating that the PDE4 inhibitors can
      substitute for LH and human chorionic gonadotropin (hCG) in this process.
      Moreover, when coadministered with a subeffective dose of hCG, PDE4 inhibitors
      acted synergistically to enhance the ovulation response. Inhibitors of PDE3 or
      PDE5 had no ovulatory effect under similar conditions. Oocytes that were ovulated
      after PDE4 inhibition could be fertilized in vitro at a rate similar to that of
      oocytes from hCG-induced ovulation. Moreover, such oocytes were fully capable of
      being fertilized in vivo and developing into normal live pups. These results
      indicate that small molecule PDE4 inhibitors may be orally active alternatives to
      hCG as part of a fertility treatment regimen.

PMID- 15448113
TI  - Synthesis and secretion of angiotensin II by the prostate gland in vitro.
AB  - The renin angiotensin system has been shown to have tissue-related functions that
      are distinct from its systemic roles. We showed that angiotensin II type 1 (AT1)
      receptors are present in mammalian sperm, and angiotensin II stimulates sperm
      motility and capacitation. In addition, angiotensin II is present in human
      seminal plasma at concentrations higher than found in blood. In testing the
      possibility that the prostate may be the source of seminal plasma angiotensin II,
      mRNA coding for angiotensinogen, (pro)renin, and angiotensin-converting enzyme
      were identified by RT-PCR in rat and human prostate and in prostate LNCaP cells,
      as well as the angiotensin receptors types 1 and 2 (AT1 and AT2) in human tissues
      and AT1 in rat. In human tissue, immunocytochemistry showed cellular
      colocalization of renin with the AT1 receptor in secretory epithelial cells.
      Confirmation of the capacity of the prostate to secrete angiotensin II was shown
      by the detection of immunoreactive angiotensin in media removed from rat prostate
      organ cultures and LNCaP cells. Rat prostate angiotensin secretion was enhanced
      by dihydrotestosterone, but LNCaP angiotensin was stimulated by estradiol. This
      stimulation was blocked by tamoxifen. Rat prostate AT1 receptor expression was
      much greater in prepuberal than in postpuberal rats but was not affected by a low
      sodium diet. It was, however, significantly enhanced by captopril pretreatment.
      These findings all suggest the independence of prostate and systemic renin
      angiotensin system regulation. The data presented here suggest that the prostate
      may be a source of the secreted angiotensin II found in seminal plasma.

PMID- 15448114
TI  - Identification of the rabbit liver UDP-glucuronosyltransferase catalyzing the
      glucuronidation of 4-ethoxyphenylurea (dulcin).
AB  - Dulcin (DL), 4-ethoxyphenylurea, a synthetic chemical about 200 times as sweet as
      sucrose, has been proposed for use as an artificial sweetener. DL is excreted as
      a urinary ureido-N-glucuronide after oral administration to rabbits. The
      phenylurea N-glucuronide is the only ureido conjugate with glucuronic acid known
      at present; therefore, DL is interesting as a probe to search for new functions
      of UDP-glucuronosyltransferases (UGTs). Seven UGT isoforms (UGT1A3, UGT1A4,
      UGT1A6, UGT1A7, UGT2B13, UGT2B14, and UGT2B16) have been identified from rabbit
      liver, but these UGTs have not been investigated using DL as a substrate. In this
      work, the identities of UGT isoforms catalyzing the formation of DL glucuronide
      were investigated using rabbit liver microsomes (RabLM) and cloned/expressed as
      rabbit UGT isoforms. DL-N-glucuronide (DNG) production was determined
      quantitatively in RabLM and homogenates of COS-7 cells expressing each UGT
      isoform by using electrospray liquid chromatography-tandem mass spectrometry.
      Analysis of DNG formation using RabLM, by Eadie-Hofstee plot, gave a Vmax of
      0.911 nmol/min/mg protein and the Km of 1.66 mM. DNG formation was catalyzed only
      by cloned expressed rabbit UGT1A7 and UGT2B16 (Vmax of 3.98 and 1.16 pmol/min/mg
      protein and a Km of 1.23 and 1.69 mM, respectively). Substrate inhibition of
      UGT1A7 by octylgallate confirmed the significant contribution of UGT1A7 to the
      formation of DNG. Octylgallate was further shown to competitively inhibit DNG
      production by RabLM (Ki = 0.149 mM). These results demonstrate that UGT1A7 is the
      major isoform catalyzing the N-glucuronidation of DL in RabLM.

PMID- 15448115
TI  - Liver grafts preserved in Celsior solution as source of hepatocytes for drug
      metabolism studies: comparison with surgical liver biopsies.
AB  - Suitability of human liver grafts preserved in Celsior solution (CS) for
      preparing metabolically competent hepatocyte cultures has been examined. To this
      end, basal and induced activity and mRNA levels of major hepatic cytochrome P450
      (P450) enzymes have been measured. By 24 h in culture, measurable levels of the
      10 P450 mRNAs studied were found in all hepatocyte preparations examined, with
      CYP2E1, CYP2C9, and CYP3A4 mRNAs being the most abundant. Compared with
      hepatocytes obtained from surgical liver resections (SLRs), lower content of each
      P450 mRNA was found in hepatocytes from the CS group; however, the relative
      distribution of individual P450 mRNAs was similar. Similar results were observed
      after measuring P450 activities. CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2E1, and
      CYP3A4 activities in hepatocytes from CS-flushed grafts were lower than but
      comparable with those of cultures prepared from SLRs. No differences in the
      metabolite profile of testosterone were found. Treatment of hepatocytes from CS
      preserved grafts with model P450 inducers shows that 2 microM methylcholanthrene
      only increased CYP1A1 and CYP1A2 mRNAs (>100-fold over control), 1 mM
      phenobarbital markedly increased CYP2A6, CYP2B6, and CYP3A4 mRNA content (>7
      fold), and 50 microM rifampicin highly increased CYP3A4 mRNA levels (>10-fold),
      whereas minor effects (<3-fold) were observed in CYP2A6, CYP2B6, and CYP2C9
      mRNAs. This induction pattern of P450s was similar, in terms of magnitude,
      reproducibility, and specificity, to that shown in primary hepatocytes from
      surgical biopsies. Overall, our results indicate that, cold-preserved in CS,
      liver grafts constitute a valuable source of human hepatocytes for drug
      metabolism studies.

PMID- 15448116
TI  - Conversion of the HIV protease inhibitor nelfinavir to a bioactive metabolite by
      human liver CYP2C19.
AB  - Antiretroviral therapy for human immunodeficiency virus (HIV) infection includes
      treatment with both reverse transcriptase inhibitors and protease inhibitors,
      which markedly suppress viral replication and circulating HIV RNA levels.
      Cytochrome P450 (P450) enzymes in human liver, chiefly CYP3A4, play a pivotal
      role in protease inhibitor biotransformation, converting these agents to largely
      inactive metabolites. However, the protease inhibitor nelfinavir (Viracept) is
      metabolized mainly to nelfinavir hydroxy-t-butylamide (M8), which exhibits potent
      antiviral activity, and to other minor products (termed M1 and M3) that are
      inactive. Since indirect evidence suggests that CYP2C19 underlies M8 formation,
      we examined the role of this inducible, polymorphic P450 enzyme in nelfinavir t
      butylamide hydroxylation by human liver. Rates of microsomal M8 formation were
      50.6 +/- 28.3 pmol of product formed/min/nmol P450 (n = 5 subjects), whereas
      kinetic analysis of the reaction revealed a KM of 21.6 microM and a Vmax of 24.6
      pmol/min/nmol P450. In reconstituted systems, CYP2C19 catalyzed nelfinavir t
      butylamide hydroxylation at a turnover rate of 2.2 min(-1), whereas CYP2C9,
      CYP2C8, and CYP3A4 were inactive toward nelfinavir. Polyclonal anti-CYP2C9 (cross
      reactive with CYP2C19) and monoclonal anti-CYP2C19 completely inhibited
      microsomal M8 production, whereas monoclonal CYP2C9 and polyclonal CYP3A4
      antibodies were without effect. Similarly, the CYP2C19 substrate omeprazole
      strongly inhibited (75%) hepatic nelfinavir t-butylamide hydroxylation at a
      concentration of only 12.5 microM. Our study shows that CYP2C19 underlies
      formation in human liver of M8, a bioactive nelfinavir metabolite. The
      inducibility of CYP2C19 by agents (e.g., rifampicin) often taken concurrently
      with nelfinavir, together with this P450's known polymorphic nature, may thus be
      important determinants of nelfinavir's antiviral potency.

PMID- 15448117
TI  - Increase in interstitial interleukin-6 of human skeletal muscle with repetitive
      low-force exercise.
AB  - Interleukin (IL)-6, which is released from muscle tissue during intense exercise,
      possesses important metabolic and probably anti-inflammatory properties. To
      evaluate the IL-6 response to low-intensity exercise, we conducted two studies:
      1) a control study with insertion of microdialysis catheters in muscle and
      determination of interstitial muscle IL-6 response over 2 h of rest and 2) an
      exercise study to investigate the IL-6 response to 20 min of repetitive low-force
      exercise. In both studies, a microdialysis catheter (cutoff: 3,000 kDa) was
      inserted into the upper trapezius muscle of six male subjects, and the catheters
      were perfused with Ringer-acetate at 5 microl/min. Venous plasma samples were
      taken in the exercise study. The insertion of microdialysis catheters into muscle
      resulted in an increase in IL-6 from 8 +/- 0 to 359 +/- 171 and 484 +/- 202 pg/ml
      after 65 and 110 min, respectively (P < 0.001). Similarly, in the exercise study,
      IL-6 increased to 289 +/- 128 pg/ml after a 55-min rest (P < 0.001). During the
      subsequent repetitive low-force exercise, muscle IL-6 further increased to 1,246
      +/- 461 pg/ml and reached 2,132 +/- 477 pg/ml after a 30-min recovery (all P <
      0.001). In contrast to this, plasma IL-6 did not significantly change in response
      to exercise. We conclude that upper extremity, low-intensity exercise results in
      a substantial increase in IL-6 in the interstitium of the stabilizing trapezius
      muscle, whereas no change is seen for plasma IL-6.

PMID- 15448118
TI  - Left ventricular adaptations following short-term endurance training.
AB  - This study examined the effects of short-term endurance training (ET) on the left
      ventricular (LV) adaptation and functional response to a series of exercise
      challenges with increasing intensity. Eight untrained men, with a mean age of
      19.4 +/- 0.5 (SE) yr, were studied before and after 6 days of ET consisting of
      cycling 2 h/day at 65% peak aerobic power (VO2max). LV ejection fraction and LV
      volumes were assessed by radionuclide angiography at rest and during exercise at
      three uninterrupted successive work rates corresponding to 53, 68, and 83% of
      VO2max, each lasting 20 min. ET produced a calculated plasma volume expansion of
      11.4 +/- 2.2% (P < 0.05). The increase in plasma volume was accompanied by an
      increase in VO2max from 45.9 +/- 1.9 to 49.0 +/- 1.0 ml x kg(-1) x min(-1) (P <
      0.01) and a decrease in maximal heart rate (197 +/- 2.3 to 188 +/- 1.0 beats/min;
      P < 0.01). Resting LV function was not changed, although there was a trend for
      higher stroke volumes (SVs) and improvement in the rapid filling phase of
      diastole (P = 0.08). Training induced an increase in exercise SV by 10.4, 10.2,
      and 7% at 53, 68, and 83% VO2max, respectively (P < 0.01). These changes were
      secondary to increases in end-diastolic volume, which increased significantly at
      each exercise work rate following training (139 +/- 6 to 154 +/- 6 ml at 53%
      VO2max, and from 136 +/- 5 to 156 +/- 5 ml at 83% VO2max; P < 0.01). End-systolic
      volumes were unchanged after ET. A significant bradycardia was observed both at
      rest (decreasing 7%) and exercise (decreasing 10.4%). LV ejection fraction during
      exercise was increased slightly by training, reaching significance at the highest
      work rate, after 60 min of exercise. (P < 0.05). Cardiac output was higher
      following training at the highest workload (20.8 +/- 2.2 vs. 22.9 +/- 3.1 l/min;
      P < 0.01). These data indicate that short-term training elicits rapid adaptation
      to the LV functional response exercise, with increases in SV being secondary to a
      Frank-Starling effect with minor changes in contractile performance. This
      produced a volume-induced bradycardia and increase in LV filling, which may be of
      benefit during prolonged exercise.

PMID- 15448119
TI  - Noninvasive measurement of temperature and fractional dissociation of imidazole
      in human lower leg muscles using 1H-nuclear magnetic resonance spectroscopy.
AB  - The temperature change of the fractional dissociation of imidazole (alpha
      imidazole) in resting human lower leg muscles was measured noninvasively using
      (1)H-nuclear magnetic resonance spectroscopy at 3.0 and 1.5 T on five normal male
      volunteers aged 30.6 +/- 10.4 yr (mean +/- SD). Using (1)H-nuclear magnetic
      resonance spectroscopy, water, carnosine, and creatine in the muscles could be
      simultaneously analyzed. Carnosine contains imidazole protons. The chemical
      shifts of water and carnosine imidazole protons relative to creatine could be
      used for estimating temperatures and alpha-imidazole, respectively. Using the
      chemical shift, the values of temperature in gastrocnemius (Gast) and soleus
      muscles at ambient temperature (21-25 degrees C) were estimated to be 35.5 +/-
      0.5 and 37.4 +/- 0.6 degrees C (means +/- SE), respectively (significantly
      different; P < 0.01). The estimated values of alpha-imidazole in these muscles
      were 0.620 +/- 0.007 and 0.630 +/- 0.013 (means +/- SE), respectively (not
      significant). Alternation of the surface temperature of the lower leg from 40 to
      10 degrees C significantly changed the temperature in Gast (P < 0.0001) from 38.1
      +/- 0.5 to 28.0 +/- 1.2 degrees C, and the alpha-imidazole in Gast decreased from
      0.631 +/- 0.003 to 0.580 +/- 0.011 (P < 0.05). However, the values of alpha
      imidazole and the temperature in soleus muscles were not significantly affected
      by this maneuver. These results indicate that the alpha-imidazole in Gast changed
      significantly with alternation in muscle temperature (r = 0.877, P < 0.00001),
      and its change was estimated to be 0.0058/ degrees C.

PMID- 15448120
TI  - Region-specific mechanical properties of the human patella tendon.
AB  - The present study investigated the mechanical properties of tendon fascicles from
      the anterior and posterior human patellar tendon. Collagen fascicles from the
      anterior and posterior human patellar tendon in healthy young men (mean +/- SD,
      29.0 +/- 4.6 yr, n = 6) were tested in a mechanical rig. A stereoscopic
      microscope equipped with a digital camera recorded elongation. The fascicles were
      preconditioned five cycles before the failure test based on pilot data on rat
      tendon fascicle. Human fascicle length increased with repeated cycles (P < 0.05);
      cycle 5 differed from cycle 1 (P < 0.05), but not cycles 2-4. Peak stress and
      yield stress were greater for anterior (76.0 +/- 9.5 and 56.6 +/- 10.4 MPa,
      respectively) than posterior fascicles (38.5 +/- 3.9 and 31.6 +/- 2.9 MPa,
      respectively), P < 0.05, while yield strain was similar (anterior 6.8 +/- 1.0%,
      posterior 8.7 +/- 1.4%). Tangent modulus was greater for the anterior (1,231 +/-
      188 MPa) than the posterior (583 +/- 122 MPa) fascicles, P < 0.05. In conclusion,
      tendon fascicles from the anterior portion of the human patellar tendon in young
      men displayed considerably greater peak and yield stress and tangent modulus
      compared with the posterior portion of the tendon, indicating region-specific
      material properties.

PMID- 15448121
TI  - Arterial pressure and muscle sympathetic nerve activity are increased after two
      hours of sustained but not cyclic hypoxia in healthy humans.
AB  - Sustained and episodic hypoxic exposures lead, by two different mechanisms, to an
      increase in ventilation after the exposure is terminated. Our aim was to
      investigate whether the pattern of hypoxia, cyclic or sustained, influences
      sympathetic activity and hemodynamics in the postexposure period. We measured
      sympathetic activity (peroneal microneurography), hemodynamics [plethysmographic
      forearm blood flow (FBF), arterial pressure, heart rate], and peripheral
      chemosensitivity in normal volunteers on two occasions during and after 2 h of
      either exposure. By design, mean arterial oxygen saturation was lower during
      sustained relative to cyclic hypoxia. Baseline to recovery muscle sympathetic
      nerve activity and blood pressure went from 15.7 +/- 1.2 to 22.6 +/- 1.9
      bursts/min (P < 0.01) and from 85.6 +/- 3.2 to 96.1 +/- 3.3 mmHg (P < 0.05) after
      sustained hypoxia, respectively, but did not exhibit significant change from 13.6
      +/- 1.5 to 17.3 +/- 2.5 bursts/min and 84.9 +/- 2.8 to 89.8 +/- 2.5 mmHg after
      cyclic hypoxia. A significant increase in FBF occurred after sustained, but not
      cyclic, hypoxia, from 2.3 +/- 0.2 to 3.29 +/- 0.4 and from 2.2 +/- 0.1 to 3.1 +/-
      0.5 ml.min(-1).100 g of tissue(-1), respectively. Neither exposure altered the
      ventilatory response to progressive isocapnic hypoxia. Two hours of sustained
      hypoxia increased not only muscle sympathetic nerve activity but also arterial
      blood pressure. In contrast, cyclic hypoxia produced slight but not significant
      changes in hemodynamics and sympathetic activity. These findings suggest the
      cardiovascular response to acute hypoxia may depend on the intensity, rather than
      the pattern, of the hypoxic exposure.

PMID- 15448122
TI  - Suppression of viral specific primary T-cell response following intense physical
      exercise in young but not old mice.
AB  - Intense exercise to exhaustion leads to increased susceptibility and severity of
      infections. T cells play an essential role in control of viral infections.
      Whereas immune suppression is considered as a likely mechanism for exhaustive
      exercise-induced susceptibility to infection, we know little about viral-specific
      T-cell response following exhaustive exercise in young or old mice. In this
      study, one group of female young (10-12 wk) and old (22-24 mo) C57BL/6 mice was
      exposed to a single bout of intense exercise to exhaustion and immediately
      infected with lymphocytic choriomeningitis virus (LCMV). Eight days later, at the
      peak of expansion phase of T-cell response, we used tetramers of MHC class I
      molecules containing viral peptides to directly visualize antigen-specific CD8 T
      cells and a sensitive functional assay measuring interferon-gamma production at
      the single-cell level to quantitate the CD8 and CD4 T-cell response. To evaluate
      the impact of intense exercise during both the initiation and evolution of the
      expansion phase of the T-cell response, a second group of young and old mice
      continued their daily bouts of intense exercise to exhaustion over the next 8
      days. Our data show that, in young mice, LCMV infection following exhaustive
      exercise leads to suppression of LCMV-specific CD8 and CD4 T-cell responses, and
      this suppression effect occurs at the initiation of the expansion phase of viral
      specific T cells. However, in old mice, unlike young mice, exhaustive exercise
      does not cause suppression of LCMV-specific T-cell responses.

PMID- 15448123
TI  - Mechanical interactions between collagen and proteoglycans: implications for the
      stability of lung tissue.
AB  - Collagen and elastin are thought to dominate the elasticity of the connective
      tissue including lung parenchyma. The glycosaminoglycans on the proteoglycans may
      also play a role because osmolarity of interstitial fluid can alter the repulsive
      forces on the negatively charged glycosaminoglycans, allowing them to collapse or
      inflate, which can affect the stretching and folding pattern of the fibers.
      Hence, we hypothesized that the elasticity of lung tissue arises primarily from
      1) the topology of the collagen-elastin network and 2) the mechanical interaction
      between proteoglycans and fibers. We measured the quasi-static, uniaxial stress
      strain curves of lung tissue sheets in hypotonic, normal, and hypertonic
      solutions. We found that the stress-strain curve was sensitive to osmolarity, but
      this sensitivity decreased after proteoglycan digestion. Images of
      immunofluorescently labeled collagen networks showed that the fibers follow the
      alveolar walls that form a hexagonal-like structure. Despite the large
      heterogeneity, the aspect ratio of the hexagons at 30% uniaxial strain increased
      linearly with osmolarity. We developed a two-dimensional hexagonal network model
      of the alveolar structure incorporating the mechanical properties of the collagen
      elastin fibers and their interaction with proteoglycans. The model accounted for
      the stress-strain curves observed under all experimental conditions. The model
      also predicted how aspect ratio changed with osmolarity and strain, which allowed
      us to estimate the Young's modulus of a single alveolar wall and a collagen
      fiber. We therefore identify a novel and important role for the proteoglycans:
      they stabilize the collagen-elastin network of connective tissues and contribute
      to lung elasticity and alveolar stability at low to medium lung volumes.

PMID- 15448124
TI  - Changes in cardiovascular function during the sleep onset period in young adults.
AB  - Blood pressure (BP) and heart rate (HR) are influenced by the sleep-wake cycle,
      with relatively abrupt falls occurring in association with sleep onset (SO).
      However, the pattern and rate of fall in BP and HR during SO and the processes
      that contribute to the fall in these variables have not been fully identified.
      Continuous BP and HR recordings were collected beginning 1 h before lights out
      (LO) until the end of the first non-rapid eye movement sleep period in 21 young,
      healthy participants maintained in a supine position. Five consecutive phases
      were defined: 1) the 30 min of wakefulness before LO; 2) LO to stage 1 sleep; 3)
      stage 1 to stage 2 sleep; 4) stage 2 sleep to the last microarousal before stable
      sleep; and 5) the first 30 min of undisturbed stable sleep. The data were
      analyzed on a beat-by-beat basis and reported as 2-min periods for phases 1 and 5
      and 10% epochs for phases 2, 3, and 4 (as participants had variable time periods
      in these phases). The level of baroreflex (BR) activity was assessed by the
      sequence technique and an autoregressive multivariate model. Furthermore, during
      phases 3 and 4, the BP and HR responses to arousal from sleep were determined.
      There were substantial falls in BP and HR after LO before the initial onset of
      theta;-activity (phase 3) and again after the onset of stable sleep after the
      cessation of spontaneous arousals. During phases 3 and 4 when there were repeated
      arousals from sleep, the fall in both variables was retarded. Furthermore, both
      the rate and magnitude of the fall in BP were negatively associated with the
      number of arousals during phases 3 and 4. There was a small increase in the
      sensitivity of the BR and indirect evidence of a substantial fall in its set
      point.

PMID- 15448125
TI  - Estrogen's attenuating effect on the exercise pressor reflex is more opioid
      dependent in gonadally intact than in ovariectomized female cats.
AB  - Using gonadally intact female cats, we showed previously that estrogen, applied
      topically to the spinal cord, attenuated the exercise pressor reflex. Although
      the mechanism by which estrogen exerted its attenuating effect is unknown, this
      steroid hormone has been shown to influence spinal opioid pathways, which in turn
      have been implicated in the regulation of the exercise pressor reflex. These
      findings prompted us to test the hypothesis that opioids mediate the attenuating
      effect of estrogen on the exercise pressor reflex in both gonadally intact female
      and ovariectomized cats. We therefore applied 200 microl of 17beta-estradiol
      (0.01 microg/ml) with and without the addition of 1,000 microg naloxone, a mu-
      and delta-opioid antagonist, to a spinal well covering the L6-S1 spinal cord in
      decerebrated female cats that were either gonadally intact or ovariectomized. The
      exercise pressor reflex was evoked by electrical stimulation of the L7 or S1
      ventral root, a maneuver that caused the hindlimb muscles to contract statically.
      We found that, in gonadally intact cats, the attenuating effect of estrogen was
      more pronounced than that in ovariectomized cats. We also found that, in
      gonadally intact female cats, naloxone partly reversed the attenuation of the
      pressor response to static contraction caused by spinal estrogen application. For
      example, in intact cats, the pressor response to contraction before estrogen
      application averaged 39 +/- 4 mmHg (n = 10), whereas the pressor response 60 min
      afterward averaged only 18 +/- 4 mmHg (P < 0.05). In contrast, the pressor
      response to contraction before estrogen and naloxone application averaged 33 +/-
      5 mmHg (n = 11), whereas afterward it averaged 27 +/- 6 mmHg (P < 0.05). In
      ovariectomized cats, naloxone was less effective in reversing the attenuating
      effect of estrogen on the exercise pressor reflex.

PMID- 15448126
TI  - Nonuniform effects of endurance exercise training on vasodilation in rat skeletal
      muscle.
AB  - Endurance exercise training (Ex) has been shown to increase maximal skeletal
      muscle blood flow. The purpose of this study was to test the hypothesis that
      increased endothelium-dependent vasodilation is associated with the Ex-induced
      increase in muscle blood flow. Furthermore, we hypothesized that enhanced
      endothelium-dependent dilation is confined to vessels in high-oxidative muscles
      that are recruited during Ex. To test these hypotheses, sedentary (Sed) and rats
      that underwent Ex (30 m/min x 10% grade, 60 min/day, 5 days/wk, 8-12 wk) were
      studied using three experimental approaches. Training effectiveness was evidenced
      by increased citrate synthase activity in soleus and vastus lateralis (red
      section) muscles (P < 0.05). Vasodilatory responses to the endothelium-dependent
      agent acetylcholine (ACh) in situ tended to be augmented by training in the red
      section of gastrocnemius muscle (RG; Sed: control, 0.69 +/- 0.12; ACh, 1.25 +/-
      0.15; Ex: control, 0.86 +/- 0.17; ACh, 1.76 +/- 0.27 ml x min(-1) x 100 g(-1) x
      mmHg(-1); 0.05 < P < 0.10 for Ex vs. Sed during ACh). Responses to ACh in situ
      did not differ between Sed and Ex for either the soleus muscle or white section
      of gastrocnemius muscle (WG). Dilatory responses of second-order arterioles from
      the RG in vitro to flow (4-8 microl/min) and sodium nitroprusside (SNP; 10(-7)
      through 10(-4) M), but not ACh, were augmented in Ex (vs. Sed; P < 0.05).
      Dilatory responses to ACh, flow, and SNP of arterioles from soleus and WG muscles
      did not differ between Sed and Ex. Content of the endothelial isoform of nitric
      oxide synthase (eNOS) was increased in second-order, fourth-order, and fifth
      order arterioles from the RG of Ex; eNOS content was similar between Sed and Ex
      in vessels from the soleus and WG muscles. These findings indicate that Ex
      induces endothelial adaptations in fast-twitch, oxidative, glycolytic skeletal
      muscle. These adaptations may contribute to enhanced skeletal muscle blood flow
      in endurance-trained individuals.

PMID- 15448127
TI  - Comment on: An assessment of the risks associated with the use of antibiotic
      resistance genes in genetically modified plants: report of the Working Party of
      the British Society for Antimicrobial Chemotherapy.

PMID- 15448128
TI  - Therapeutic activity of a killer peptide against experimental
      paracoccidioidomycosis.
AB  - OBJECTIVES: To evaluate whether an engineered synthetic decapeptide (KP) derived
      from the sequence of a recombinant anti-idiotypic antibody, that represents the
      internal image of a Pichia anomala killer toxin, could be fungicidal in vitro and
      therapeutic in vivo against Paracoccidioides brasiliensis and
      paracoccidioidomycosis (PCM). METHODS: Fungicidal activity of KP was assessed in
      vitro and in vivo by inhibition of colony forming units and by histological
      examination, 8 days after infection, of organs from mice intravenously injected
      with a virulent strain of P. brasiliensis (3 x 10(6) yeast cells) and
      intraperitoneally treated with KP (3.3 microg/g body weight, three doses), in
      comparison with control animals equally administered with a scrambled decapeptide
      (SP). RESULTS: KP but not SP was fungicidal in vitro at 39 ng/multiply-budding
      yeast cell and less efficiently in its D-isomeric form (0.31 microg/multiply
      budding yeast cell). It was also able to markedly reduce the fungal load in
      organs (liver, lung, spleen) of infected animals. CONCLUSIONS: The therapeutic
      effect observed opens the way for using the antifungal peptide as an alternative
      control of PCM in association with conventional antifungal drugs.

PMID- 15448129
TI  - Receptor-mediated reversible translocation of the G protein betagamma complex
      from the plasma membrane to the Golgi complex.
AB  - Heterotrimeric G proteins have been thought to function on the plasma membrane
      after activation by transmembrane receptors. Here we show that, after activation
      by receptors, the G protein betagamma complex selectively translocates to the
      Golgi. Receptor inactivation results in Gbetagamma translocating back to the
      plasma membrane. Both translocation processes occur rapidly within seconds. The
      efficiency of translocation is influenced by the type of gamma subunit present in
      the G protein. Distinctly different receptor types are capable of inducing the
      translocation. Receptor-mediated translocation of Gbetagamma can spatially
      segregate G protein signaling activity.

PMID- 15448130
TI  - Apoptotic topoisomerase I-DNA complexes induced by staurosporine-mediated oxygen
      radicals.
AB  - Topoisomerase I (Top1), an abundant nuclear enzyme expressed throughout the cell
      cycle, relaxes DNA supercoiling by forming transient covalent DNA cleavage
      complexes. We show here that staurosporine, a ubiquitous inducer of apoptosis in
      mammalian cells, stabilizes cellular Top1 cleavage complexes. These complexes are
      formed indirectly as staurosporine cannot induce Top1 cleavage complexes in
      normal DNA with recombinant Top1 or nuclear extract from normal cells. In treated
      cells, staurosporine produces oxidative DNA lesions and generates reactive oxygen
      species (ROS). Quenching of these ROS by the antioxidant N-acetyl-l-cysteine or
      inhibition of the mitochondrial dependent production of ROS by the caspase
      inhibitor benzyloxycarbonyl-VAD prevents staurosporine-induced Top1 cleavage
      complexes. Down-regulation of Top1 by small interfering RNA decreases
      staurosporine-induced apoptotic DNA fragmentation. We propose that Top1 cleavage
      complexes resulting from oxidative DNA lesions generated by ROS in staurosporine
      treated cells contribute to the full apoptotic response.

PMID- 15448131
TI  - Purification of active TFIID from Saccharomyces cerevisiae. Extensive promoter
      contacts and co-activator function.
AB  - The basal transcription factor TFIID is composed of the TATA-binding protein
      (TBP) and 14 TBP-associated factors (TAFs). Although TBP alone binds to the TATA
      box of DNA and supports basal transcription, the TAFs have essential functions
      that remain poorly defined. In order to study its properties, TFIID was purified
      from Saccharomyces cerevisiae using a newly developed affinity tag. Analysis of
      the final elution by mass spectrometry confirms the presence of all the known
      TAFs and TBP, as well as Rsp5, Bul1, Ubp3, Bre5, Cka1, and Cka2. Both Taf1 and
      Taf5 are ubiquitinated, and the ubiquitination pattern of TFIID changes when BUL1
      or BRE5 is deleted. Purified TFIID binds specifically to promoter DNA in a manner
      stabilized by TFIIA, and these complexes can be analyzed by native gel
      electrophoresis. Phenanthroline-copper footprinting and photoaffinity cross
      linking indicate that TFIID makes extensive contacts upstream and downstream of
      the TATA box. TFIID supports basal transcription and activated transcription,
      both of which are enhanced by TFIIA.

PMID- 15448132
TI  - Rho small GTPases activate the epithelial Na(+) channel.
AB  - Small G proteins in the Rho family are known to regulate diverse cellular
      processes, including cytoskeletal organization and cell cycling, and more
      recently, ion channel activity and activity of phosphatidylinositol 4-phosphate 5
      kinase (PI(4)P 5-K). The present study investigates regulation of the epithelial
      Na(+) channel (ENaC) by Rho GTPases. We demonstrate here that RhoA and Rac1
      markedly increase ENaC activity. Activation by RhoA was suppressed by the C3
      exoenzyme. Inhibition of the downstream RhoA effector Rho kinase, which is
      necessary for RhoA activation of PI(4)P 5-K, abolished ENaC activation. Similar
      to RhoA, overexpression of PI(4)P 5-K increased ENaC activity suggesting that
      production of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P(2)) in response to
      RhoA-Rho kinase signaling stimulates ENaC. Supporting this idea, inhibition of
      phosphatidylinositol 4-kinase, but not the RhoA effector phosphatidylinositol 3
      kinase and MAPK cascades, markedly attenuated RhoA-dependent activation of ENaC.
      RhoA increased ENaC activity by increasing the plasma membrane levels of this
      channel. We conclude that RhoA activates ENaC via Rho kinase and subsequently
      activates PI(4)P 5-K with concomitant increases in PI(4,5)P(2) levels promoting
      channel insertion into the plasma membrane.

PMID- 15448133
TI  - Structural basis of biopterin-induced inhibition of GTP cyclohydrolase I by GFRP,
      its feedback regulatory protein.
AB  - GTP cyclohydrolase I (GTPCHI) is the rate-limiting enzyme involved in the
      biosynthesis of tetrahydrobiopterin, a key cofactor necessary for nitric oxide
      synthase and for the hydroxylases that are involved in the production of
      catecholamines and serotonin. In animals, the GTPCHI feedback regulatory protein
      (GFRP) binds GTPCHI to mediate feed-forward activation of GTPCHI activity in the
      presence of phenylalanine, whereas it induces feedback inhibition of enzyme
      activity in the presence of biopterin. Here, we have reported the crystal
      structure of the biopterin-induced inhibitory complex of GTPCHI and GFRP and
      compared it with the previously reported phenylalanine-induced stimulatory
      complex. The structure reveals five biopterin molecules located at each interface
      between GTPCHI and GFRP. Induced fitting structural changes by the biopterin
      binding expand large conformational changes in GTPCHI peptide segments forming
      the active site, resulting in inhibition of the activity. By locating 3,4
      dihydroxy-phenylalanine-responsive dystonia mutations in the complex structure,
      we found mutations that may possibly disturb the GFRP-mediated regulation of
      GTPCHI.

PMID- 15448134
TI  - Ectodomain shedding and intramembrane cleavage of mammalian Notch proteins is not
      regulated through oligomerization.
AB  - Intramembrane cleaving proteases such as site 2 protease, gamma-secretase, and
      signal peptide peptidase hydrolyze peptide bonds within the transmembrane domain
      (TMD) of signaling molecules such as SREBP, Notch, and HLA-E, respectively. All
      three enzymes require a prior cleavage at the juxtamembrane region by another
      protease. It has been proposed that removing the extracellular domain allows
      dissociation of substrate TMD, held together by the extracellular domain or loop.
      Using gamma-secretase as a model intramembrane cleaving protease and Notch as a
      model substrate, we investigated whether activating and inactivating mutations in
      Notch modulate gamma-secretase cleavage through changes in oligomerization. We
      find that although the Notch epidermal growth factor repeats can promote dimer
      formation, most surface Notch molecules in mammalian cells are monomeric as are
      constitutively active or inactive Notch1 proteins. Using a bacterial assay for TM
      dimerization, we find that the isolated TMD of Notch and amyloid precursor
      protein self-associate and that mutations affecting Notch cleavage by gamma
      secretase cleavage do not alter TMD dimerization. Our results indicate that
      ligand-induced reversal of controlled TMD dimerization by the Notch extracellular
      domain is unlikely to underlie the regulatory mechanism of intramembranous
      cleavage.

PMID- 15448135
TI  - Dna2p helicase/nuclease is a tracking protein, like FEN1, for flap cleavage
      during Okazaki fragment maturation.
AB  - During cellular DNA replication the lagging strand is generated as discontinuous
      segments called Okazaki fragments. Each contains an initiator RNA primer that is
      removed prior to joining of the strands. Primer removal in eukaryotes requires
      displacement of the primer into a flap that is cleaved off by flap endonuclease 1
      (FEN1). FEN1 employs a unique tracking mechanism that requires the recognition of
      the free 5' terminus and then movement to the base of the flap for cleavage.
      Abnormally long flaps are coated by replication protein A (RPA), inhibiting FEN1
      cleavage. A second nuclease, Dna2p, is needed to cleave an RPA-coated flap
      producing a short RPA-free flap, favored by FEN1. Here we show that Dna2p is also
      a tracking protein. Annealed primers or conjugated biotin-streptavidin complex
      block Dna2p entry and movement. Single-stranded binding protein-coated flaps
      inhibit Dna2p cleavage. Like FEN1, Dna2p can track over substrates with a non
      Watson Crick base, such as a biotin, or a missing base within a chain. Unlike
      FEN1, Dna2p shows evidence of a "threading-like" mechanism that does not support
      tracking over a branched substrate. We propose that the two nucleases both track,
      Dna2p first and then FEN1, to remove initiator RNA via long flap intermediates.

PMID- 15448136
TI  - Sharp-1/DEC2 inhibits skeletal muscle differentiation through repression of
      myogenic transcription factors.
AB  - Skeletal muscle differentiation is regulated by the basic-helix-loop-helix (bHLH)
      family of transcription factors. The myogenic bHLH factors form heterodimers with
      the ubiquitously expressed bHLH E-proteins and bind E-box (CANNTG) sites present
      in the promoters of several muscle-specific genes. Our previous studies have
      shown that the bHLH factor Sharp-1 is expressed in skeletal muscle and interacts
      with MyoD and E-proteins. However, its role in regulation of myogenic
      differentiation remains unknown. We report here that endogenous Sharp-1 is
      expressed in proliferating C2C12 myoblasts and is down-regulated during myogenic
      differentiation. Constitutive expression of Sharp-1 in C2C12 myoblasts promotes
      cell cycle exit causing a decrease in cyclin D1 expression but blocks terminal
      differentiation. Although MyoD expression is not inhibited, the induction of
      differentiation-specific genes such as myogenin, MEF2C, and myosin heavy chain is
      impaired by Sharp-1 overexpression. We demonstrate that the interaction of Sharp
      1 with MyoD and E-proteins results in reduced DNA binding and transactivation
      from MyoD-dependent E-box sites. Re-expression of MyoD approximately E47 rescues
      the differentiation defect imposed by Sharp-1, suggesting that myogenic bHLH
      factors function downstream of Sharp-1. Our data suggest that protein-protein
      interactions between Sharp-1, MyoD, and E47 resulting in interference with MyoD
      function underlies Sharp-1-mediated repression of myogenic differentiation.

PMID- 15448137
TI  - Atf1-Pcr1-M26 complex links stress-activated MAPK and cAMP-dependent protein
      kinase pathways via chromatin remodeling of cgs2+.
AB  - Although co-ordinate interaction between different signal transduction pathways
      is essential for developmental decisions, interpathway connections are often
      obscured and difficult to identify due to cross-talk. Here signals from the
      fission yeast stress-activated MAPK Spc1 are shown to regulate Cgs2, a negative
      regulator of the cAMP-dependent protein kinase (protein kinase A) pathway.
      Pathway integration is achieved via Spc1-dependent binding of Atf1-Pcr1
      heterodimer to an M26 DNA site in the cgs2+ promoter, which remodels chromatin to
      regulate expression of cgs2+ and targets downstream of protein kinase A. This
      direct interpathway connection co-ordinates signals of nitrogen and carbon source
      depletion to affect a G0 cell-cycle checkpoint and sexual differentiation. The
      Atf1-Pcr1-M26 complex-dependent chromatin remodeling provides a molecular
      mechanism whereby Atf1-Pcr1 heterodimer can function differentially as either a
      transcriptional activator, or as a transcriptional repressor, or as an inducer of
      meiotic recombination. We also show that the Atf1-Pcr1-M26 complex functions as
      both an inducer and repressor of chromatin remodeling, which provides a way for
      various chromatin remodeling-dependent effector functions to be regulated.

PMID- 15448138
TI  - Familial hemiplegic migraine type 1 mutations K1336E, W1684R, and V1696I alter
      Cav2.1 Ca2+ channel gating: evidence for beta-subunit isoform-specific effects.
AB  - Mutations in the Cav2.1 alpha1-subunit of P/Q-type Ca2+ channels cause human
      diseases, including familial hemiplegic migraine type-1 (FHM1). FHM1 mutations
      alter channel gating and enhanced channel activity at negative potentials appears
      to be a common pathogenetic mechanism. Different beta-subunit isoforms (primarily
      beta4 and beta3) participate in the formation of Cav2.1 channel complexes in
      mammalian brain. Here we investigated not only whether FHM1 mutations K1336E
      (KE), W1684R (WR), and V1696I (VI) can affect Cav2.1 channel function but focused
      on the important question whether mutation-induced changes on channel gating
      depend on the beta-subunit isoform. Mutants were co-expressed in Xenopus oocytes
      together with beta1, beta3, or beta4 and alpha2delta1 subunits, and channel
      function was analyzed using the two-electrode voltage-clamp technique. WR shifted
      the voltage dependence for steady-state inactivation of Ba2+ inward currents
      (IBa) to more negative voltages with all beta-subunits tested. In contrast, a
      similar shift was observed for KE only when expressed with beta3. All mutations
      promoted IBa decay during pulse trains only when expressed with beta1 or beta3
      but not with beta4. Enhanced decay could be explained by delayed recovery from
      inactivation. KE accelerated IBa inactivation only when co-expressed with beta3,
      and VI slowed inactivation only with beta1 or beta3. KE and WR shifted channel
      activation of IBa to more negative voltages. As the beta-subunit composition of
      Cav2.1 channels varies in different brain regions, our data predict that the
      functional FHM1 phenotype also varies between different neurons or even within
      different neuronal compartments.

PMID- 15448139
TI  - Ca(2+)-dependent conformational changes in guanylyl cyclase-activating protein 2
      (GCAP-2) revealed by site-specific phosphorylation and partial proteolysis.
AB  - Guanylyl cyclase-activating proteins (GCAPs) are calcium sensor proteins of the
      EF-hand superfamily that inhibit retinal photoreceptor membrane guanylyl cyclase
      (retGC) in the dark when they bind Ca(2+) but activate retGC when Ca(2+)
      dissociates from GCAPs in response to light stimulus. We addressed the difference
      in exposure of GCAP-2 structure to protein kinase and a protease as indicators of
      conformational change caused by binding and release of Ca(2+). We have found that
      unlike its homolog, GCAP-1, the C terminus of GCAP-2 undergoes phosphorylation by
      cyclic nucleotide-dependent protein kinases (CNDPK) present in the retinal
      extract and rapid dephosphorylation by the protein phosphatase PP2C present in
      the retina. Inactivation of the CNDPK phosphorylation site in GCAP-2 by
      substitutions S201G or S201D, as well as phosphorylation or thiophosphorylation
      of Ser(201), had little effect on the ability of GCAP-2 to regulate retGC in
      reconstituted membranes in vitro. At the same time, Ca(2+) strongly inhibited
      phosphorylation of the wild-type GCAP-2 by retinal CNDPK but did not affect
      phosphorylation of a constitutively active Ca(2+)-insensitive GCAP-2 mutant.
      Partial digestion of purified GCAP-2 with Glu-C protease revealed at least two
      sites that become exposed or constrained in a Ca(2+)-sensitive manner. The Ca(2+)
      dependent conformational changes in GCAP-2 affect the areas around Glu(62)
      residue in the entering helix of EF-hand 2, the areas proximal to the exiting
      helix of EF-hand 3, and Glu(136)-Glu (138) between EF-hand 3 and EF-hand 4. These
      changes also cause the release of the C-terminal Ser(201) from the constraint
      caused by the Ca(2+)-bound conformation.

PMID- 15448140
TI  - The nucleus-encoded protein MOC1 is essential for mitochondrial light acclimation
      in Chlamydomonas reinhardtii.
AB  - Mitochondrial respiration plays an important role in optimizing photosynthetic
      efficiency in plants. As yet, the mechanisms by which plant mitochondria sense
      and respond to changes in the environment are unclear, particularly when exposed
      to light. Here we describe the characterization of the Chlamydomonas reinhardtii
      mutant stm6, which was identified on the basis of impaired state transitions, a
      mechanism that regulates light harvesting in the chloroplast. The gene disrupted
      in stm6, termed Moc1, encodes a homologue of the human mitochondrial
      transcription termination factor (mTERF). MOC1 is targeted to the mitochondrion,
      and its expression is up-regulated in response to light. Loss of MOC1 causes a
      high light-sensitive phenotype and disrupts the transcription and expression
      profiles of the mitochondrial respiratory complexes causing, as compared with
      wild type, light-mediated changes in the expression levels of nuclear and
      mitochondrial encoded cytochrome c oxidase subunits and ubiquinone-NAD subunits.
      The absence of MOC1 leads to a reduction in the levels of cytochrome c oxidase
      and of rotenone-insensitive external NADPH dehydrogenase activities of the
      mitochondrial respiratory electron transfer chain. Overall, we have identified a
      novel mitochondrial factor that regulates the composition of the mitochondrial
      respiratory chain in the light so that it can act as an effective sink for
      reductant produced by the chloroplast.

PMID- 15448141
TI  - Hsp104 binds to yeast Sup35 prion fiber but needs other factor(s) to sever it.
AB  - The interaction of Hsp104 with yeast prion fibers made of Sup35NM, a prion
      inducing domain of Sup35, was tested. When fluorescently labeled Hsp104 was added
      to the preformed fibers, individual fibers were fluorescently decorated uniformly
      along the fiber length. However, the density of fluorescence differed from one
      fiber to another, indicating the presence of subspecies of Sup35NM fibers. The
      time course of fiber formation from monomer Sup35NM was delayed by Hsp104. Hsp104
      mediated fragmentation of fibers was tested using bead-tethered fibers. In
      contrast with the recent report (Shorter, J., and Lindquist, S. (2004) Science
      304, 1793-1797), Hsp104 alone was unable to sever the fibers. Yeast cell lysate
      or the Hsp104-deficient cell lysate plus Hsp104 caused ATP-dependent, guanidine
      hydrochloride-sensitive fragmentation of the fibers. Thus, in our experimental
      setup, Hsp104 plus other factor(s) in the yeast cytosol are required for severing
      yeast prion fiber. The reason of discrepancy from the above report is unknown but
      is possibly caused by different conformational subspecies of prion fibers.

PMID- 15448142
TI  - Mcm2 is a direct substrate of ATM and ATR during DNA damage and DNA replication
      checkpoint responses.
AB  - In vertebrates, ATM and ATR are critical regulators of checkpoint responses to
      damaged and incompletely replicated DNA. These checkpoint responses involve the
      activation of signaling pathways that inhibit the replication of chromosomes with
      DNA lesions. In this study, we describe the isolation of a cDNA encoding a full
      length version of Xenopus ATM. Using antibodies against the regulatory domain of
      ATM, we have identified the essential replication protein Mcm2 as an ATM-binding
      protein in Xenopus egg extracts. Xenopus Mcm2 underwent phosphorylation at
      Ser(92) in response to the presence of double-stranded DNA breaks or DNA
      replication blocks in egg extracts. This phosphorylation involved both ATM and
      ATR, but the relative contribution of each kinase depended upon the checkpoint
      inducing DNA signal. Furthermore, both ATM and ATR phosphorylated Mcm2 directly
      at Ser(92) in cell-free kinase assays. Immunodepletion of both ATM and ATR
      abrogated the checkpoint response that blocks chromosomal DNA replication in egg
      extracts containing double-stranded DNA breaks. These experiments indicate that
      ATM and ATR phosphorylate the functionally critical replication protein Mcm2
      during both DNA damage and replication checkpoint responses in Xenopus egg
      extracts.

PMID- 15448143
TI  - Identification and characterization of a novel monoamine transporter in the human
      brain.
AB  - Precise control of monoamine neurotransmitter levels in the extracellular fluids
      of the brain is critical in maintaining efficient and robust neurotransmission.
      High affinity transporters in the solute carrier SLC6A family function in
      removing monoamines from the neurosynaptic cleft. Emerging evidence suggests that
      these transporters are only one part of a system of transporters that work in
      concert to maintain brain homeostasis of monoamines. Here we report the cloning
      and characterization of a new human plasma membrane monoamine transporter, PMAT.
      The PMAT cDNA encodes a protein of 530 amino acid residues with 10-12
      transmembrane segments. PMAT is not homologous to known neurotransmitter
      transporters but exhibits low homology to members of the equilibrative nucleoside
      transporter family. When expressed in Madin-Darby canine kidney cells and Xenopus
      laevis oocytes, PMAT efficiently transports serotonin (K(m) = 114 mum), dopamine
      (K(m) = 329 mum), and the neurotoxin 1-methyl-4-phenylpyridinium (K(m) = 33 mum).
      In contrast, there is no significant interaction of PMAT with nucleosides or
      nucleobases. PMAT-mediated monoamine transport does not require Na(+) or Cl(-)
      but appears to be sensitive to changes in membrane potential. Northern blot
      analysis showed that PMAT is predominantly expressed in the human brain and
      widely distributed in the central nervous system. These studies demonstrate that
      PMAT may be a novel low affinity transporter for biogenic amines, which, under
      certain conditions, might supplement the role of the high affinity transporters
      in the brain.

PMID- 15448144
TI  - Arginine 260 of the amino-terminal domain of NR1 subunit is critical for tissue
      type plasminogen activator-mediated enhancement of N-methyl-D-aspartate receptor
      signaling.
AB  - Tissue-type plasminogen activator (tPA) has been involved in both physiological
      and pathological glutamatergic-dependent processes, such as synaptic plasticity,
      seizure, trauma, and stroke. In a previous study, we have shown that the
      proteolytic activity of tPA enhances the N-methyl-D-aspartate (NMDA) receptor
      mediated signaling in neurons (Nicole, O., Docagne, F., Ali, C., Margaill, I.,
      Carmeliet, P., MacKenzie, E. T., Vivien, D., and Buisson, A. (2001) Nat. Med. 7,
      59-64). Here, we show that tPA forms a direct complex with the amino-terminal
      domain (ATD) of the NR1 subunit of the NMDA receptor and cleaves this subunit at
      the arginine 260. Furthermore, point mutation analyses show that arginine 260 is
      necessary for both tPA-induced cleavage of the ATD of NR1 and tPA-induced
      potentiation of NMDA receptor signaling. Thus, tPA is the first binding protein
      described so far to interact with the ATD of NR1 and to modulate the NMDA
      receptor function.

PMID- 15448145
TI  - Production of the carbonate radical anion during xanthine oxidase turnover in the
      presence of bicarbonate.
AB  - Xanthine oxidase is generally recognized as a key enzyme in purine catabolism,
      but its structural complexity, low substrate specificity, and specialized tissue
      distribution suggest other functions that remain to be fully identified. The
      potential of xanthine oxidase to generate superoxide radical anion, hydrogen
      peroxide, and peroxynitrite has been extensively explored in pathophysiological
      contexts. Here we demonstrate that xanthine oxidase turnover at physiological pH
      produces a strong one-electron oxidant, the carbonate radical anion. The radical
      was shown to be produced from acetaldehyde oxidation by xanthine oxidase in the
      presence of catalase and bicarbonate on the basis of several lines of evidence
      such as oxidation of both dihydrorhodamine 123 and 5,5-dimethyl-1-pyrroline-N
      oxide and chemiluminescence and isotope labeling/mass spectrometry studies. In
      the case of xanthine oxidase acting upon xanthine and hypoxanthine as substrates,
      carbonate radical anion production was also evidenced by the oxidation of 5,5
      dimethyl-1-pyrroline-N-oxide and of dihydrorhodamine 123 in the presence of
      uricase. The results indicated that Fenton chemistry occurring in the bulk
      solution is not necessary for carbonate radical anion production. Under the
      conditions employed, the radical was likely to be produced at the enzyme active
      site by reduction of a peroxymonocarbonate intermediate whose formation and
      reduction is facilitated by the many xanthine oxidase redox centers. In addition
      to indicating that the carbonate radical anion may be an important mediator of
      the pathophysiological effects of xanthine oxidase, the results emphasize the
      potential of the bicarbonate-carbon dioxide pair as a source of biological
      oxidants.

PMID- 15448146
TI  - Vascular endothelial growth factor- and thrombin-induced termination factor, Down
      syndrome critical region-1, attenuates endothelial cell proliferation and
      angiogenesis.
AB  - Activation and dysfunction of the endothelium underlie many vascular disorders
      including atherosclerosis, tumor growth, and inflammation. Endothelial cell
      activation is mediated by many different extra-cellular signals, which result in
      overlapping yet distinct patterns of gene expression. Here we show, in DNA
      microarray analyses, that vascular endothelial growth factor (VEGF) and thrombin
      result in dramatic and rapid upregulation of Down syndrome critical region (DSCR)
      1 gene encoding exons 4-7, a negative feedback regulator of calcium-calcineurin
      NF-AT signaling. VEGF- and thrombin-mediated induction of DSCR-1 involves the
      cooperative binding of NF-ATc and GATA-2/3 to neighboring consensus motifs in the
      upstream promoter. Constitutive expression of DSCR-1 in endothelial cells
      markedly impaired NF-ATc nuclear localization, proliferation, and tube formation.
      Under in vivo conditions, overexpression of DSCR-1 reduced vascular density in
      matrigel plugs and melanoma tumor growth in mice. Taken together, these findings
      support a model in which VEGF- and thrombin-mediated induction of endothelial
      cell proliferation triggers a negative feedback loop consisting of DSCR-1 gene
      induction and secondary inhibition of NF-AT signaling. As a natural brake in the
      angiogenic process, this negative pathway may lend itself to therapeutic
      manipulation in pathological states.

PMID- 15448147
TI  - Transcriptional profiling of circadian patterns of mRNA expression in the chick
      retina.
AB  - Previous transcriptome analyses have identified candidate molecular components of
      the avian pineal clock, and herein we employ high density cDNA microarrays of
      pineal gland transcripts to determine oscillating transcripts in the chick retina
      under daily and constant darkness conditions. Subsequent comparative
      transcriptome analysis of the pineal and retinal oscillators distinguished
      several transcriptional similarities between the two as well as significant
      differences. Rhythmic retinal transcripts were classified according to functional
      categories including phototransductive elements, transcription/translation
      factors, carrier proteins, cell signaling molecules, and stress response genes.
      Candidate retinal clock transcripts were also organized relative to time of day
      mRNA abundance, revealing groups accumulating peak mRNA levels across the
      circadian day but primarily reaching peak values at subjective dawn or subjective
      dusk. Comparison of the chick retina transcriptome to the pineal transcriptome
      under constant conditions yields an interesting group of conserved genes. This
      group includes putative clock elements cry1 and per3 in addition to several
      previously unidentified and uninvestigated genes exhibiting profiles of mRNA
      abundance that varied markedly under daily and constant conditions. In contrast,
      many transcripts were differentially regulated, including those believed to be
      involved in both melatonin biosynthesis and circadian clock mechanisms. Our
      results indicate an intimate transcriptional relationship between the avian
      pineal and retina in addition to providing previously uncharacterized molecular
      elements that we hypothesize to be involved in circadian rhythm generation.

PMID- 15448148
TI  - Small molecule modulators of endogenous and co-chaperone-stimulated Hsp70 ATPase
      activity.
AB  - The molecular chaperone and cytoprotective activities of the Hsp70 and Hsp40
      chaperones represent therapeutic targets for human diseases such as cancer and
      those that arise from defects in protein folding; however, very few Hsp70 and no
      Hsp40 modulators have been described. Using an assay for ATP hydrolysis, we
      identified and screened small molecules with structural similarity to 15
      deoxyspergualin and NSC 630668-R/1 for their effects on endogenous and Hsp40
      stimulated Hsp70 ATPase activity. Several of these compounds modulated Hsp70
      ATPase activity, consistent with the action of NSC 630668-R/1 observed previously
      (Fewell, S. W., Day, B. W., and Brodsky, J. L. (2001) J. Biol. Chem. 276, 910
      914). In contrast, three compounds inhibited the ability of Hsp40 to stimulate
      Hsp70 ATPase activity but did not affect the endogenous activity of Hsp70. Two of
      these agents also compromised the Hsp70/Hsp40-mediated post-translational
      translocation of a secreted pre-protein in vitro. Together, these data indicate
      the potential for continued screening of small molecule Hsp70 effectors and that
      specific modulators of Hsp70-Hsp40 interaction can be obtained, potentially for
      future therapeutic use.

PMID- 15448149
TI  - Retinal ganglion cells are autonomous circadian oscillators synthesizing N
      acetylserotonin during the day.
AB  - Retinal ganglion cells send visual and circadian information to the brain
      regarding the environmental light-dark cycles. We investigated the capability of
      retinal ganglion cells of synthesizing melatonin, a highly reliable circadian
      marker that regulates retinal physiology, as well as the capacity of these cells
      to function as autonomous circadian oscillators. Chick retinal ganglion cells
      presented higher levels of melatonin assessed by radioimmunoassay during both the
      subjective day in constant darkness and the light phase of a light-dark cycle.
      Similar changes were observed in mRNA levels and activity of arylalkylamine N
      acetyltransferase, a key enzyme in melatonin biosynthesis, with the highest
      levels of both parameters during the subjective day. These daily variations were
      preceded by the elevation of cyclic-AMP content, the second messenger involved in
      the regulation of melatonin biosynthesis. Moreover, cultures of immunopurified
      retinal ganglion cells at embryonic day 8 synchronized by medium exchange
      synthesized a [3H]melatonin-like indole from [3H]tryptophan. This [3H]indole was
      rapidly released to the culture medium and exhibited a daily variation, with
      levels peaking 8 h after synchronization, which declined a few hours later.
      Cultures of embryonic retinal ganglion cells also showed self-sustained daily
      rhythms in arylalkylamine N-acetyltransferase mRNA expression during at least
      three cycles with a period near 24 h. These rhythms were also observed after the
      application of glutamate. The results demonstrate that chick retinal ganglion
      cells may function as autonomous circadian oscillators synthesizing a melatonin
      like indole during the day.

PMID- 15448150
TI  - Functional characterization of a prokaryotic Kir channel.
AB  - The Kir gene family encodes inward rectifying K+ (Kir) channels that are
      widespread and critical regulators of excitability in eukaryotic cells. A related
      gene family (KirBac) has recently been identified in prokaryotes. While a crystal
      structure of one member, Kir-Bac1.1, has been solved, there has been no
      functional characterization of any KirBac gene products. Here we present
      functional characterization of KirBac1.1 reconstituted in liposomes. Utilizing a
      86Rb+ uptake assay, we demonstrate that KirBac1.1 generates a K+ -selective
      permeation path that is inhibited by extraliposomal Ba2+ and Ca2+ ions. In
      contrast to KcsA (an acid-activated bacterial potassium channel), KirBac1.1 is
      inhibited by extraliposomal acid (pKa approximately 6). This characterization of
      KirBac1.1 activity now paves the way for further correlation of structure and
      function in this model Kir channel.

PMID- 15448151
TI  - Use of a randomized hybrid ribozyme library for identification of genes involved
      in muscle differentiation.
AB  - We have employed the hybrid hammerhead ribozyme-based gene discovery system for
      identification of genes functionally involved in muscle differentiation using in
      vitro myoblast differentiation assay. The major muscle regulatory genes (MyoD1,
      Mylk, myosin, myogenin, and Myf5) were identified endorsing the validity of this
      method. Other gene targets included tumor suppressors and cell cycle regulators
      (p19ARF and p21WAF1), FGFR-4, fibronectin, Prkg2, Pdk4, fem, and six novel
      proteins. Functional involvement of three of the identified targets in myoblast
      differentiation was confirmed by their specific knockdown using ribozymes and
      siRNA. Besides demonstrating a simple and an effective method of isolation of
      gene functions involved in muscle differentiation, we report for the first time
      that overexpression of Fem, a member of the sex-determining family of proteins,
      caused accelerated myotube formation, and its targeting deferred myoblast
      differentiation. This functional gene screening is not only helpful in
      understanding the molecular pathways of muscle differentiation but also to design
      molecular strategies for myopathologic therapies.

PMID- 15448152
TI  - Activation-induced cytidine deaminase deaminates 5-methylcytosine in DNA and is
      expressed in pluripotent tissues: implications for epigenetic reprogramming.
AB  - DNA deaminases of the Aid/Apobec family convert cytosine into uracil and play key
      roles in acquired and innate immunity. The epigenetic modification by methylation
      of cytosine in CpG dinucleotides is also mutagenic, but this is thought to occur
      by spontaneous deamination. Here we show that Aid and Apobec1 are 5
      methylcytosine deaminases resulting in a thymine base opposite a guanine. Their
      action can thus lead to C --> T transition mutations in methylated DNA, or in
      conjunction with repair of the T:G mismatch, to demethylation. The Aid and
      Apobec1 genes are located in a cluster of pluripotency genes including Nanog and
      Stella and are co-expressed with these genes in oocytes, embryonic germ cells,
      and embryonic stem cells. These results suggest that Aid and perhaps some of its
      family members may have roles in epigenetic reprogramming and cell plasticity.
      Transition in CpG dinucleotides is the most frequent mutation in human genetic
      diseases, and sequence context analysis of CpG transitions in the APC tumor
      suppressor gene suggests that DNA deaminases may play a significant role in tumor
      etiology.

PMID- 15448153
TI  - The DP-1 transcription factor is required for keratinocyte growth and epidermal
      stratification.
AB  - The epidermis is a stratified epithelium constantly replenished through the
      ability of keratinocytes in its basal layer to proliferate and self-renew. The
      epidermis arises from a single-cell layer ectoderm during embryogenesis. Large
      proliferative capacity is central to ectodermal cell and basal keratinocyte
      function. DP-1, a heterodimeric partner of E2F transcription factors, is highly
      expressed in the ectoderm and all epidermal layers during embryogenesis. To
      investigate the role of DP-1 in epidermal morphogenesis, we inhibited DP-1
      activity through exogenous expression of a dominant-negative mutant (dnDP-1).
      Expression of the dnDP-1 mutant interferes with binding of E2F/DP-1 heterodimers
      to DNA and inhibits DNA replication, as well as cyclin A mRNA and protein
      expression. Chromatin immunoprecipitation analysis demonstrated that the cyclin A
      promoter is predominantly bound in proliferating keratinocytes by complexes
      containing E2F-3 and E2F-4. Thus, the mechanisms of decreased expression of
      cyclin A in the presence of dnDP-1 seem to involve inactivation of DP-1 complexes
      containing E2F-3 and E2F-4. To assess the consequences on epidermal morphogenesis
      of inhibiting DP-1 activity, we expressed dnDP-1 in rat epithelial keratinocytes
      in organotypic culture and observed that DP-1 inhibition negatively affected
      stratification of these cells. Likewise, expression of dnDP-1 in embryonic
      ectoderm explants produced extensive disorganization of subsequently formed
      epidermal basal and suprabasal layers, interfering with normal epidermal
      formation. We conclude that DP-1 activity is required for normal epidermal
      morphogenesis and ectoderm-to-epidermis transition.

PMID- 15448154
TI  - The relative influence of metal ion binding sites in the I-like domain and the
      interface with the hybrid domain on rolling and firm adhesion by integrin
      alpha4beta7.
AB  - We examined the effect of conformational change at the beta(7) I-like/hybrid
      domain interface on regulating the transition between rolling and firm adhesion
      by integrin alpha(4)beta(7). An N-glycosylation site was introduced into the I
      like/hybrid domain interface to act as a wedge and to stabilize the open
      conformation of this interface and hence the open conformation of the alpha(4)
      beta(7) headpiece. Wild-type alpha(4)beta(7) mediates rolling adhesion in Ca(2+)
      and Ca(2+)/Mg(2+) but firm adhesion in Mg(2+) and Mn(2+). Stabilizing the open
      headpiece resulted in firm adhesion in all divalent cations. The interaction
      between metal binding sites in the I-like domain and the interface with the
      hybrid domain was examined in double mutants. Changes at these two sites can
      either counterbalance one another or be additive, emphasizing mutuality and the
      importance of multiple interfaces in integrin regulation. A double mutant with
      counterbalancing deactivating ligand-induced metal ion binding site (LIMBS) and
      activating wedge mutations could still be activated by Mn(2+), confirming the
      importance of the adjacent to metal ion-dependent adhesion site (ADMIDAS) in
      integrin activation by Mn(2+). Overall, the results demonstrate the importance of
      headpiece allostery in the conversion of rolling to firm adhesion.

PMID- 15448155
TI  - One site mutation disrupts dimer formation in human DPP-IV proteins.
AB  - DPP-IV is a prolyl dipeptidase, cleaving the peptide bond after the penultimate
      proline residue. It is an important drug target for the treatment of type II
      diabetes. DPP-IV is active as a dimer, and monomeric DPP-IV has been speculated
      to be inactive. In this study, we have identified the C-terminal loop of DPP-IV,
      highly conserved among prolyl dipeptidases, as essential for dimer formation and
      optimal catalysis. The conserved residue His750 on the loop contributes
      significantly for dimer stability. We have determined the quaternary structures
      of the wild type, H750A, and H750E mutant enzymes by several independent methods
      including chemical cross-linking, gel electrophoresis, size exclusion
      chromatography, and analytical ultracentrifugation. Wild-type DPP-IV exists as
      dimers both in the intact cell and in vitro after purification from human semen
      or insect cells. The H750A mutation results in a mixture of DPP-IV dimer and
      monomer. H750A dimer has the same kinetic constants as those of the wild type,
      whereas the H750A monomer has a 60-fold decrease in kcat. Replacement of His750
      with a negatively charged Glu (H750E) results in nearly exclusive monomers with a
      300-fold decrease in catalytic activity. Interestingly, there is no dynamic
      equilibrium between the dimer and the monomer for all forms of DPP-IVs studied
      here. This is the first study of the function of the C-terminal loop as well as
      monomeric mutant DPP-IVs with respect to their enzymatic activities. The study
      has important implications for the discovery of drugs targeted to the dimer
      interface.

PMID- 15448156
TI  - Prereplicative purine methylation and postreplicative demethylation in each DNA
      duplication of the Escherichia coli replication cycle.
AB  - Escherichia coli plasmid DNA activated for initiation of duplication is in a
      stable low linking number supercoiled conformation. Low linking number DNA is
      methylated at the internal purines of a frequent 5'-Pyr-Pyr-Pur-Pur tetramer with
      a 5'-Pyr-Pur-3' axis of symmetry and is cut at the axis of symmetry by
      pneumococcal restriction enzyme DpnI when methylated in both strands. Purine
      methylation is of adenine in one strand and guanine in the other. Methylation of
      one of the two purines is removed during the cell cycle, presumably before the
      reverse shift to the B-supercoiled conformation. The topological transition was
      reconstituted in vitro only with DNA unmethylated at purines. Methylation
      restriction analyses coupled with the chemical properties of low-linking number
      DNA and B-DNA respectively, suggest that removal of guanine methylation is
      essential for the low-linking number to B-DNA transition and hence for the
      deactivation of replication. Demethylation of methylguanine could explain the
      presence in E. coli of the two-member inducible operon known as ada.
      Characteristics of ada suggest a cascade of chemical DNA modifications that
      reverse prereplicative guanine methylation. Guanine demethylation could provide a
      model for the pivotal role played by de novo methylation in replication and for
      the essential role of "repair" enzyme ExoIII in demethylation leading to the
      reversal of replicative DNA activation and other processes that affect DNA
      function.

PMID- 15448157
TI  - Glycosylation deficiency at either one of the two glycan attachment sites of
      cellular prion protein preserves susceptibility to bovine spongiform
      encephalopathy and scrapie infections.
AB  - The conversion into abnormally folded prion protein (PrP) plays a key role in
      prion diseases. PrP(C) carries two N-linked glycan chains at amino acid residues
      180 and 196 (mouse). Previous in vitro data indicated that the conversion process
      may not require glycosylation of PrP. However, it is conceivable that these
      glycans function as intermolecular binding sites during the de novo infection of
      cells on susceptible organisms and/or play a role for the interaction of both PrP
      isoforms. Such receptor-like properties could contribute to the formation of
      specific prion strains. However, in earlier studies, mutations at the
      glycosylation sites of PrP led to intracellular trafficking abnormalities, which
      made it impossible to generate PrP glycosylation-deficient mice that were
      susceptible to bovine spongiform encephalopathy (BSE) or scrapie. We have now
      tested more than 25 different mutations at both consensus sites and found one
      nonglycosylated (T182N/T198A) and two monoglycosylated (T182N and T198A) mutants
      that rather retained authentic cellular trafficking properties. In vitro all
      three mutants were converted into PrP(res). PrP mutant T182N/T198A also provoked
      a strong dominant-negative inhibition on the endogenous wild type PrP conversion
      reaction. By using the two monoglycosylated mutants, we generated transgenic mice
      overexpressing PrP(C) in their brains at levels of 2-4 times that of
      nontransgenic mice. Most interestingly, such mice proved readily susceptible to a
      challenge with either scrapie (Chandler and Me7) or with BSE. Incubation times
      were comparable or in some instances even significantly shorter than those of
      nontransgenic mice. These data indicate that diglycosylation of PrP(C) is not
      mandatory for prion infection in vivo.

PMID- 15448158
TI  - Free fatty acid-induced beta-cell defects are dependent on uncoupling protein 2
      expression.
AB  - Chronic exposure to elevated free fatty acids (lipotoxicity) induces uncoupling
      protein (UCP2) in the pancreatic beta-cell, and therefore a causal link between
      UCP2 and beta-cell defects associated with obesity may exist. Recently, we showed
      that lipid treatment in vivo and in vitro in UCP2(-/-) mice/islets does not
      result in any loss in beta-cell glucose sensitivity. We have now assessed the
      mechanism of maintained beta-cell function in UCP2(-/-) mice by exposing islets
      to 0.4 mM palmitate for 48 h. Palmitate treatment increased triglyceride
      concentrations in wild type (WT) but not UCP2(-/-) islets because of higher
      palmitate oxidation rates in the UCP2(-/-) islets. Dispersed beta-cells from the
      palmitate-exposed WT islets had reduced glucose-stimulated hyperpolarization of
      the mitochondrial membrane potential compared with both control WT and palmitate
      exposed UCP2(-/-) beta-cells. The glucose-stimulated increases in the ATP/ADP
      ratio and cytosolic Ca2+ are attenuated in palmitate-treated WT but not UCP2(-/-)
      beta-cells. Exposure to palmitate reduced glucose-stimulated insulin secretion
      (GSIS) in WT islets, whereas UCP2(-/-) islets had enhanced GSIS. Overexpression
      of recombinant UCP2 but not enhanced green fluorescent protein in beta-cells
      resulted in a loss of glucose-stimulated hyperpolarization of the mitochondrial
      membrane potential and GSIS similar to that seen in WT islets exposed to
      palmitate. Reactive oxygen species (ROS) are known to increase the activity of
      UCP2. We showed that ROS levels were elevated in control UCP2(-/-) islets as
      compared with WT and UCP2(-/-) islets overexpressing UCP2 and that palmitate
      increased ROS in WT and UCP2(-/-) islets overexpressing UCP2 but not in UCP2(-/-)
      islets. Thus, UCP2(-/-) islets resisted the toxic effects of palmitate by
      maintaining glucose-dependent metabolism-secretion coupling. We propose that
      higher free fatty acid oxidation rates prevent accumulation of triglyceride in
      UCP2(-/-) islets, such accumulation being a phenomenon associated with
      lipotoxicity.

PMID- 15448159
TI  - ERK2 prohibits apoptosis-induced subcellular translocation of orphan nuclear
      receptor NGFI-B/TR3.
AB  - Transcription factor NGFI-B (neuronal growth factor-induced clone B), also called
      Nur77 or TR3, is an immediate early gene and an orphan member of the nuclear
      receptor family. The NGFI-B protein also has a function distinct from that of a
      transcription factor; it translocates to mitochondria to initiate apoptosis.
      Recently, it was demonstrated that NGFI-B interacts with Bcl-2 by inducing a
      conformational change in Bcl-2, converting it from protector to a killer. After
      exposing rat cerebellar granule neurons to glutamate (100 mum, 15 min), NGFI-B
      translocated to the mitochondria. Growth factors such as the epidermal growth
      factor activate the MAP kinase ERK, the activity of which may determine whether a
      cell survives or undergoes apoptosis. In the present study we found that the
      epidermal growth factor activated ERK2 in cerebellar granule neurons and that
      this activation prohibited glutamate-induced subcellular translocation of NGFI-B.
      Likewise, overexpressed active ERK2 resulted in a predominant nuclear
      localization of green fluorescent protein-tagged NGFI-B. Thus, activation of ERK2
      may overcome apoptosis-induced subcellular translocation of NGFI-B. This finding
      represents a novel and rapid growth factor survival pathway that is independent
      of gene regulation.

PMID- 15448160
TI  - Inhibition of cytotrophoblastic (JEG-3) cell invasion by interleukin 12 involves
      an interferon gamma-mediated pathway.
AB  - Trophoblast invasion, like tumor invasion, shares common biochemical mechanisms.
      However, in contrast to tumor invasion of a host tissue, trophoblastic invasion
      during implantation is strictly regulated, temporospatially. Factors responsible
      for these important regulatory processes are presently unknown; however, studies
      indicate that cytokines and growth factors represent in the peri-implantation
      uterine milieu as the possible candidates. In this study we investigated the role
      of interleukin (IL) 12 in regulating trophoblast invasion and the expression of
      trophoblast proteases (matrix metalloprotease (MMP)-2, MMP-9, and urokinase-type
      plasminogen activators) and their inhibitors (tissue inhibitors of
      metalloprotease (TIMP) 1, TIMP-2, and plasminogen activator inhibitor (PAI)-1)
      using an in vitro tissue culture system of human choriocarcinoma cell line JEG-3.
      Our major findings show an anti-invasive role of IL-12, associated with an
      inhibitory effect on the proteases but with an opposite up-regulating influence
      on the protease inhibitor, TIMP-1, whereas TIMP-2 and plasminogen activator
      inhibitor 1 remained unaltered. Stimulation of JEG-3 cells with IL-12 also
      induced interferon (IFN)-gamma production, which when neutralized using a
      monoclonal anti-IFN-gamma antibody, F12, abrogates its ability to down-regulate
      the MMPs. IL-12 also mediates an IFN-gamma-dependent up-regulation of E-cadherin,
      thereby implying that alteration in cell-cell adhesion besides regulating the
      proteases and the inhibitors possibly contributes to the observed anti-invasive
      role of this cytokine. TIMP-1, although stimulated by IL-12, was found to be
      unaltered by antibody F12, thereby implying a possibility of an IL-12-dependent
      IFN-gamma independent regulation. These findings thereby suggest an important
      role of IL-12 in modulation of trophoblast proteases and their inhibitors besides
      regulating cell-cell interactions and invasion during implantation, with far
      reaching possibilities for understanding the mechanism(s) and regulations of
      invasion and metastasis.

PMID- 15448161
TI  - Regulation and function of SUMO modification.

PMID- 15448162
TI  - Molecular characterization of the haptoglobin.hemoglobin receptor CD163. Ligand
      binding properties of the scavenger receptor cysteine-rich domain region.
AB  - CD163 is the macrophage receptor for endocytosis of haptoglobin.hemoglobin
      complexes. The extracellular region consisting of nine scavenger receptor
      cysteine rich (SRCR) domains also circulates in plasma as a soluble protein. By
      ligand binding analysis of a broad spectrum of soluble CD163 truncation variants,
      the amino-terminal third of the SRCR region was shown to be crucial for the
      binding of haptoglobin.hemoglobin complexes. By Western blotting of the CD163
      variants, a panel of ten monoclonal antibodies was mapped to SRCR domains 1, 3,
      4, 6, 7, and 9, respectively. Only the two antibodies binding to SRCR domain 3
      exhibited effective inhibition of ligand binding. Furthermore, analysis of
      purified native CD163 revealed that proteolytic cleavage in SRCR domain 3
      inactivates ligand binding. Calcium protects against cleavage in this domain.
      Analysis of the calcium sensitivity of ligand binding to CD163 demonstrated that
      optimal ligand binding requires physiological plasma calcium concentrations, and
      an immediate ligand release occurs at the low calcium concentrations measured in
      acidifying endosomes. In conclusion, SRCR domain 3 of CD163 is an exposed domain
      and a critical determinant for the calcium-sensitive coupling of
      haptoglobin.hemoglobin complexes.

PMID- 15448163
TI  - A novel pharmatope tag inserted into the beta4 subunit confers allosteric
      modulation to neuronal nicotinic receptors.
AB  - alpha-Bungarotoxin, the classic nicotinic antagonist, has high specificity for
      muscle type alpha1 subunits in nicotinic acetylcholine receptors. In this study,
      we show that an 11-amino-acid pharmatope sequence, containing residues important
      for alpha-bungarotoxin binding to alpha1, confers functional alpha-bungarotoxin
      sensitivity when strategically placed into a neuronal non-alpha subunit, normally
      insensitive to this toxin. Remarkably, the mechanism of toxin inhibition is
      allosteric, not competitive as with neuromuscular nicotinic receptors. Our
      findings argue that alpha-bungarotoxin binding to the pharmatope, inserted at a
      subunit-subunit interface diametrically distinct from the agonist binding site,
      interferes with subunit interface movements critical for receptor activation. Our
      results, taken together with the structural similarities between nicotinic and
      GABAA receptors, suggest that this allosteric mechanism is conserved in the Cys
      loop ion channel family. Furthermore, as a general strategy, the engineering of
      allosteric inhibitory sites through pharmatope tagging offers a powerful new tool
      for the study of membrane proteins.

PMID- 15448164
TI  - Characterization of mammalian sulfiredoxin and its reactivation of hyperoxidized
      peroxiredoxin through reduction of cysteine sulfinic acid in the active site to
      cysteine.
AB  - Peroxiredoxins (Prxs) are a family of peroxidases that reduce hydroperoxides. The
      cysteine residue in the active site of certain eukaryotic Prx enzymes undergoes
      reversible oxidation to sulfinic acid (Cys-SO2H) during catalysis, and
      sulfiredoxin (Srx) has been identified as responsible for reversal of the
      resulting enzyme inactivation in yeast. We have now characterized mammalian
      orthologs of yeast Srx with an assay based on monitoring of the reduction of
      sulfinic Prx by immunoblot analysis with antibodies specific for the sulfinic
      state. Sulfinic reduction by mammalian Srx was found to be a slow process (kcat =
      0.18/min) that requires ATP hydrolysis. ATP could be efficiently replaced by GTP,
      dATP, or dGTP but not by CTP, UTP, dCTP, or dTTP. Both glutathione and
      thioredoxin are potential physiological electron donors for the Srx reaction,
      given that their Km values (1.8 mM and 1.2 microM, respectively) are in the range
      of their intracellular concentrations, and the Vmax values obtained with the two
      reductants were similar. Although its pKa is relatively low (approximately 7.3),
      the active site cysteine of Srx remained reduced even when the active site
      cysteine of most Prx molecules became oxidized. Finally, depletion of human Srx
      by RNA interference suggested that Srx is largely responsible for reduction of
      the Cys-SO2H of Prx in A549 human cells.

PMID- 15448165
TI  - Myristoylation, a protruding loop, and structural plasticity are essential
      features of a nonenveloped virus fusion peptide motif.
AB  - Members of the fusion-associated small transmembrane (FAST) protein family are a
      distinct class of membrane fusion proteins encoded by nonenveloped fusogenic
      reoviruses. The 125-residue p14 FAST protein of reptilian reovirus has an
      approximately 38-residue myristoylated N-terminal ectodomain containing a
      moderately apolar N-proximal region, termed the hydrophobic patch. Mutagenic
      analysis indicated sequence-specific elements in the N-proximal portion of the
      p14 hydrophobic patch affected cell-cell fusion activity, independent of overall
      effects on the relative hydrophobicity of the motif. Circular dichroism (CD) of a
      myristoylated peptide representing the majority of the p14 ectodomain suggested
      this region is mostly disordered in solution but assumes increased structure in
      an apolar environment. From NMR spectroscopic data and simulated annealing, the
      soluble nonmyristoylated p14 ectodomain peptide consists of an N-proximal
      extended loop flanked by two proline hinges. The remaining two-thirds of the
      ectodomain peptide structure is disordered, consistent with predictions based on
      CD spectra of the myristoylated peptide. The myristoylated p14 ectodomain
      peptide, but not a nonmyristoylated version of the same peptide nor a
      myristoylated scrambled peptide, mediated extensive lipid mixing in a liposome
      fusion assay. Based on the lipid mixing activity, structural plasticity,
      environmentally induced conformational changes, and kinked structures predicted
      for the p14 ectodomain and hydrophobic patch (all features associated with fusion
      peptides), we propose that the majority of the p14 ectodomain is composed of a
      fusion peptide motif, the first such motif dependent on myristoylation for
      membrane fusion activity.

PMID- 15448166
TI  - HucR, a novel uric acid-responsive member of the MarR family of transcriptional
      regulators from Deinococcus radiodurans.
AB  - The MarR family of transcriptional regulators comprises a subset of winged helix
      DNA-binding proteins and includes numerous members that function in environmental
      surveillance of aromatic compounds. We describe the characterization of HucR, a
      novel MarR homolog from Deinococcus radiodurans that demonstrates phenolic
      sensing capabilities. HucR binds as a homodimer to a single site within its
      promoter/operator region with Kd = 0.29 +/- 0.02 nM. The HucR binding site
      contains a pseudopalindromic sequence, composed of 8-bp half-sites separated by 2
      bp. The location of the HucR binding site in the intergenic region between hucR
      and a putative uricase suggests a mechanism of simultaneous co-repression of
      these two genes. The substrate of uricase, uric acid, is an efficient antagonist
      of DNA binding, reducing HucR-DNA complex formation to 50% at 0.26 mM ligand,
      compared with 5.2 and 46 mM for the aromatic compounds salicylate and
      acetylsalicylate, respectively. Enhanced levels in vivo of hucR and uricase
      transcript and increased uricase activity under conditions of excess uric acid
      further indicate a novel regulatory mechanism of aromatic catabolism in D.
      radiodurans. Since uric acid is a scavenger of reactive oxygen species, we
      hypothesize that HucR is a participant in the intrinsic resistance of D.
      radiodurans to high levels of oxidative stress.

PMID- 15448167
TI  - The luteinizing hormone-releasing hormone inhibits the anti-apoptotic activity of
      insulin-like growth factor-1 in pituitary alphaT3 cells by protein kinase Calpha
      mediated negative regulation of Akt.
AB  - The luteinizing hormone-releasing hormone (LHRH) receptor is a G protein-coupled
      receptor involved in the synthesis and release of pituitary gonadotropins and in
      the proliferation and apoptosis of pituitary cells. Insulin-like growth factor-1
      receptor (IGF-1R) is a tyrosine kinase receptor that has a mitogenic effect on
      pituitary cells. In this study, we used the alphaT3 gonadotrope cell line as a
      model to characterize the IGF-1R signaling pathways and to investigate whether
      this receptor interacts with the LHRH cascade. We found that IGF-1 activated the
      IGF-1R, insulin receptor substrate (IRS)-1, phosphatidylinositol 3-kinase, and
      Akt in a time-dependent manner in alphaT3 cells. The MAPK (ERK1/2, p38, and JNK)
      pathways were only weakly activated by IGF-1. In contrast, LHRH strongly
      stimulated the MAPK pathways but had no effect on Akt activation. Cotreatment
      with IGF-1 and LHRH had various effects on these signaling pathways. 1) It
      strongly increased IGF-1-induced tyrosine phosphorylation of IRS-1 and IRS-1
      associated phosphatidylinositol 3-kinase through activation of the epidermal
      growth factor receptor. 2) It had an additive effect on ERK1/2 activation without
      modifying the phosphorylation of p38 and JNK1/2. 3) It strongly reduced IGF-1
      activation of Akt. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      assays and cell cycle analysis revealed that, in addition to having an additive
      effect on ERK1/2 activation, cotreatment with IGF-1 and LHRH also had an additive
      effect on cell proliferation. The LHRH-induced inhibition of Akt stimulated by
      IGF-1 was completely blocked by Safingol, a protein kinase C (PKC) alpha-specific
      inhibitor, and by a dominant negative form of PKCalpha. Finally, we showed that
      the inhibitory effect of LHRH on IGF-1-induced PKCalpha-mediated Akt activation
      was associated with a marked reduction in Bad phosphorylation and a substantial
      decrease in the ability of IGF-1 to rescue alphaT3 cells from apoptosis induced
      by serum starvation. Our results demonstrate for the first time that several
      interactions take place between IGF-1 and LHRH receptors in gonadotrope cells.

PMID- 15448168
TI  - Phosphorylation of DNA topoisomerase I by the c-Abl tyrosine kinase confers
      camptothecin sensitivity.
AB  - DNA topoisomerase I (topo I) is involved in the regulation of DNA supercoiling,
      gene transcription, recombination, and DNA repair. The anticancer agent
      camptothecin specifically targets topo I. The mechanisms responsible for the
      regulation of topo I in cells, however, are not known. This study demonstrates
      that c-Abl-dependent phosphorylation up-regulates topo I activity. The c-Abl SH3
      domain bound directly to the N-terminal region of topo I. The results demonstrate
      that c-Abl phosphorylated topo I at Tyr268 in core subdomain II. c-Abl-mediated
      phosphorylation of topo I Tyr268 in vitro and in cells conferred activation of
      the topo I isomerase function. Moreover, activation of c-Abl by treatment of
      cells with ionizing radiation was associated with c-Abl-dependent phosphorylation
      of topo I and induction of topo I activity. The functional significance of the c
      Abl/topo I interaction is supported by the findings that (i) mutant topo I(Y268F)
      exhibited loss of c-Abl-induced topo I activity, and (ii) c-Abl-/- cells were
      deficient in the accumulation of protein-linked DNA breaks. In addition, loss of
      topo I phosphorylation in c-Abl-deficient cells conferred resistance to
      camptothecin-induced apoptosis. These findings collectively support a model in
      which c-Abl-mediated phosphorylation of topo I is functionally important to topo
      I activity and sensitivity to topo I poisons.

PMID- 15448169
TI  - Chromosome aneuploidy in the spermatozoa of two men with globozoospermia.
AB  - The objective of this study was to determine the aneuploidy level in spermatozoa
      in two men with globozoospermia. Sperm nuclei were analysed by fluorescence in
      situ hybridization (FISH) in two infertile males with globozoospermia. Dual FISH
      for chromosomes 7 and 9, 13 and 21, and triple FISH for chromosomes X, Y, and 18
      was performed. The main outcome measured was meiotic segregation differences
      between both globozoospermic men and controls. A statistically significant
      difference in disomies 13 and 21 was found between patients 1 and 2. The diploidy
      rate of spermatozoa of patient 1 (0.876%) was significantly increased compared
      with that of patient 2 (0.304%) and control men (0.293%). In conclusion there
      seems to be a slightly increased frequency of aneuploidy in round-headed
      spermatozoa. However, it is unlikely that these aneuploid spermatozoa would be
      used in assisted reproduction techniques.

PMID- 15448170
TI  - The impact of DeltaG on the oral bioavailability of low bioavailable therapeutic
      agents.
AB  - Low oral bioavailability continues to drive research toward identifying novel
      approaches to enhance drug delivery. Over the past few years, emphasis on the use
      of absorption enhancers has been overwhelming despite their major adverse
      effects. Zonula occludens toxin (Zot) was recently established as a safe and
      effective absorption enhancer, reversibly opening the tight junctions for
      hydrophilic markers and hydrophobic drugs across the small intestine and the
      blood brain barrier. DeltaG, the biologically active fragment of Zot, was
      isolated and shown to increase the in vitro transport and in vivo absorption of
      paracellular markers. The objective of this study was to examine the effect of
      DeltaG on the oral bioavailability of low bioavailable therapeutic agents.
      Jugular vein cannulated Sprague-Dawley rats were randomly assigned to receive the
      following treatments intraduodenally (ID): [(3)H]cyclosporin A, [(3)H]ritonavir,
      [(3)H]saquinavir, or [(3)H]acyclovir at (120 microCi/kg) alone, with protease
      inhibitors (PIs), or with DeltaG (720 microg/kg)/PI. Serial blood samples were
      collected, and plasma was analyzed for radioactivity. After ID administration
      with DeltaG/PI, C(max) significantly (p < 0.05) increased over a range of 197 to
      5700%, whereas area under the plasma concentration time curve displayed
      significant increases extending over a range of 123.8 to 4990.3% for the
      investigated drugs. DeltaG significantly increased the in vivo oral absorption of
      some low bioavailable drugs in the presence of PI. This study suggests that
      DeltaG-mediated tight junction modulation, combined with metabolic protection,
      may be used to enhance the low oral bioavailability of certain drugs when
      administered concurrently.

PMID- 15448171
TI  - Investigation of efflux transport of dehydroepiandrosterone sulfate and
      mitoxantrone at the mouse blood-brain barrier: a minor role of breast cancer
      resistance protein.
AB  - Breast cancer resistance protein (Bcrp/Abcg2) is a new efflux transporter found
      at the blood-brain barrier (BBB) of humans and pigs. Since it has been
      hypothesized that Bcrp may act as a new type of efflux transporter at the BBB, we
      investigated the involvement of Bcrp in the efflux transport of typical
      substrates, dehydroepiandrosterone sulfate (DHEAS) and mitoxantrone, across the
      mouse BBB. The expression of Bcrp in mouse brain capillaries was confirmed by
      quantitative polymerase chain reaction, Western blot, and immunohistochemical
      analysis. The role of Bcrp as an efflux transporter was evaluated using the in
      situ brain perfusion method in wild-type and P-glycoprotein (P-gp) knockout mice
      with or without treatment with GF120918 (Elacridar), an inhibitor of both Bcrp
      and P-gp. The increased brain uptake of [(3)H]DHEAS and [(3)H]mitoxantrone by
      GF120918 in wild-type and P-gp knockout mice suggested the existence of a
      GF120918-sensitive and P-gp-independent efflux transporter for DHEAS and
      mitoxantrone across the BBB. However, the brain uptake of [(3)H]DHEAS in Bcrp
      knockout mice was comparable with that in wild-type mice, and the effect of
      GF120918 was still observed in Bcrp knockout mice. In addition, the brain uptake
      of [(3)H]mitoxantrone was also similar in wild-type and Bcrp knockout mice. These
      results suggest that although BCRP is expressed at the BBB it plays a minor role
      in active efflux transport of DHEAS and mitoxantrone out of brain and that one or
      more GF120918-sensitive efflux transporters distinct from BCRP or P-gp
      contributes to the brain efflux of DHEAS and mitoxantrone.

PMID- 15448172
TI  - A plant type 2 metallothionein (MT) from cork tissue responds to oxidative
      stress.
AB  - Expression of plant metallothionein genes has been reported in a variety of
      senescing tissues, such as leaves and stems, ripening fruits, and wounded
      tissues, and has been proposed to function in both metal chaperoning and
      scavenging of reactive oxygen species. In this work, it is shown that MT is also
      associated with suberization, after identifying a gene actively transcribed in
      Quercus suber cork cells as a novel MT. This cDNA, isolated from a phellem cDNA
      library, encodes a MT that belongs to type 2 plant MTs (QsMT). Expression of the
      QsMT cDNA in E. coli grown in media supplemented with Zn, Cd, or Cu has yielded
      recombinant QsMT. Characterization of the respective metal aggregates agrees well
      with a copper-related biological role, consistent with the capacity of QsMT to
      restore copper tolerance to a MT-deficient, copper-sensitive yeast mutant.
      Furthermore, in situ hybridization results demonstrate that RNA expression of
      QsMT is mainly observed under conditions related to oxidative stress, either
      endogenous, as found in cork or in actively proliferating tissues, or exogenous,
      for example, in response to H(2)O(2) or paraquat treatments. The putative role of
      QsMT in oxidative stress, both as a free radical scavenger via its sulphydryl
      groups or as a copper chelator is discussed.

PMID- 15448173
TI  - Increased sucrose level and altered nitrogen metabolism in Arabidopsis thaliana
      transgenic plants expressing antisense chloroplastic fructose-1,6-bisphosphatase.
AB  - The pea chloroplastic fructose-1,6-bisphosphatase (FBPase) antisense construct
      reduced the endogenous level of expression of the corresponding Arabidopsis
      thaliana gene. The reduction of foliar FBPase activity in the transformants T(2)
      and T(3) generation ranged from 20% to 42%, and correlated with lower levels of
      FBPase protein. FBPase antisense plants displayed different phenotypes with a
      clear increase in leaf fresh weight. Measurements of photosynthesis revealed a
      higher carbon-assimilation rate. Decreased FBPase activity boosted the foliar
      carbohydrate contents, with a shift in the sucrose:starch ratio, which reached a
      maximum of 0.99 when the activity loss was 41%. Nitrate reductase activity
      decreased simultaneously with an increase in glutamine synthetase activity, which
      could be explained in terms of ammonium assimilation regulation by sugar content.
      These results suggest the role of FBPase as a key enzyme in CO(2) assimilation,
      and also in co-ordinating carbon and nitrogen metabolism.

PMID- 15448174
TI  - Apparent respiratory discrimination is correlated with growth rate in the shoot
      apex of sunflower (Helianthus annuus).
AB  - The literature offers no consensus as to whether the delta(13)C of respired CO(2)
      is identical to that of the respiratory substrate, perhaps because of differences
      in measurement technique and growth conditions. To address this issue, the
      delta(13)C of respired CO(2) from growing sunflower shoot apices was measured and
      compared with that of soluble carbohydrates extracted from the respiring tissues.
      Shoot apices were studied because any influence of growth and biosynthesis was
      expected to be maximally expressed in these rapidly growing tissues. The two most
      probable substrates, starch and soluble sugars, were similar in delta(13)C
      (P=0.46). The delta(13)C of respired CO(2) was enriched in (13)C compared with
      these putative substrates (P<0.0001). This apparent enrichment ranged from 2.2
      per thousand-5.7 per thousand, and decreased with relative growth rate
      (P<0.0001). The respiratory enrichment was counterbalanced by a depletion in the
      tissue constructed from the residual carbohydrates. The depletion varied from 2.2
      per thousand to 3.0 per thousand relative to soluble carbohydrates (P<0.05), as
      predicted from mass-balance arguments. These results support the idea that
      respired CO(2) is enriched relative to its substrates. Variation in growth rates
      may help to explain the variable amounts of respiratory discrimination described
      in the literature.

PMID- 15448175
TI  - Oxygen radicals produced by plant plasma membranes: an EPR spin-trap study.
AB  - Plant plasma membranes are known to produce superoxide radicals, while the
      production of the hydroxyl radical, previously detected in complex plant tissues,
      is thought to occur in the cell wall. The mechanism of production of superoxide
      radicals by plant plasma membranes is, however, under dispute. It is shown, using
      electron paramagnetic resonance spectroscopy with a 5-diethoxyphosphoryl-5-methyl
      1-pyrroline N-oxide spin-trap capable of differentiating between radical species,
      that isolated purified plasma membranes from maize roots produce hydroxyl
      radicals besides superoxide radicals. The results argue in favour of superoxide
      production through an oxygen and diphenylene iodonium-sensitive, NADH-dependent
      superoxide synthase mechanism, as well as through other unidentified
      mechanism(s). The hydroxyl radical is produced by an oxygen-insensitive, NADH
      stimulated mechanism, which is enhanced in membranes in which the superoxide
      synthase is incapacitated by substrate removal or inhibition.

PMID- 15448176
TI  - Genetic analysis of the function of major leaf proteases in barley (Hordeum
      vulgare L.) nitrogen remobilization.
AB  - Most of the nitrogen harvested with the seeds of annual crops is remobilized and
      retranslocated within the plant between anthesis and plant death. While
      chloroplasts contain most of the reduced nitrogen present in photosynthetically
      active leaf cells, the (major) pathway(s) involved in the degradation of their
      proteins prior to the retranslocation of the resulting amino acids are unknown.
      In this study, a population of 146 recombinant inbred barley lines (RIL), derived
      from the cross between two varieties with a highly inheritable difference in
      grain protein concentration, was used to map quantitative trait loci (QTL) for
      leaf amino-, carboxy- and endopeptidase activities relative to previously
      determined QTL for grain protein, leaf N storage, and remobilization. The results
      strongly suggested that major endopeptidases, assayed at both acidic and slightly
      alkaline pH values (favouring vacuolar and extravacuolar enzymes, respectively)
      are not instrumental in leaf N remobilization or the control of grain protein
      accumulation. Similarly, QTL determined for aminopeptidases (relative to QTL for
      N remobilization) indicated no functional role for the enzyme(s) assayed in plant
      N recycling. By contrast, careful evaluation of QTL data suggested that one or
      several carboxypeptidase isoenzymes may be involved in this physiologically and
      economically important process. As these proteases (in contrast to
      aminopeptidases) have previously been localized in vacuoles, this result appears
      intriguing. These data, while shedding new light on an old problem, also indicate
      that the described approach may prove useful in evaluating the functional roles
      of additional (not assayed in this study) proteolytic systems in whole-plant
      nitrogen recycling.

PMID- 15448177
TI  - Rubisco activase chaperone activity is regulated by a post-translational
      mechanism in maize leaves.
AB  - Rubisco activase (RCA) is a molecular chaperone present in maize as 43 kDa and 41
      kDa polypeptides. They are encoded by two different genes comprising an identical
      ORF that corresponds to the 43 kDa RCA polypeptide, and their transcripts do not
      show putative splicing sites. To determine the origin of the 41 kDa polypeptide,
      leaf poly A(+) mRNA was in vitro translated. Results demonstrated de novo
      synthesis only for the 43 kDa RCA. Antibodies developed against peptides from
      either the carboxy- or the amino-terminal end of 43 kDa RCA showed by western
      blot that the 43 kDa polypeptide amino-terminal region is missing in the 41 kDa
      polypeptide, whereas both RCA polypeptides shared the carboxy-end region.
      Regulation of RCA polypeptide ratios was determined in plant leaves at different
      developmental stages and under stressing environmental conditions. Increased
      levels of 43/41 kDa RCA ratio were found in leaves under low light exposure,
      whereas this ratio declined under water stress. Measurements of chaperone
      activity either on each RCA polypeptide alone or in a mixture showed the
      functional relevance of different 43/41 kDa RCA polypeptide ratios. Greater
      chaperone activity was found for the 41 kDa than for the 43 kDa polypeptide.
      Taken together, these results indicate that 41 kDa RCA polypeptide formation is
      regulated by limited proteolysis of the 43 kDa RCA at its amino-terminal region.
      This pathway is sensitive to developmental and environmental signals, and seems
      to play a relevant function during plant stress.

PMID- 15448178
TI  - Genes commonly regulated by water-deficit stress in Arabidopsis thaliana.
AB  - Cellular water-deficit stress triggers many changes in gene expression which can
      be used to define the response of a plant to an environmental condition.
      Microarray technology permits the study of expression patterns of thousands of
      genes simultaneously, permitting a comprehensive understanding of the types and
      quantities of RNAs that are present in a cell in response to water-deficit
      stress. The expression of specific genes was compared in three different
      experiments designed to understand changes in gene expression in response to
      water-deficit stress. Surprisingly, there was a relatively small set of genes
      that were commonly induced or repressed. There were 27 genes commonly induced and
      three commonly repressed; 1.4% and 0.2% of the genes analysed in common to all
      three experiments. The induced genes fell into six different functional
      categories: metabolism, transport, signalling, transcription, hydrophilic
      proteins, and unknown. The three commonly repressed genes indicated that
      repression of gene expression supported a frequently observed response to water
      deficit stress, decreased growth. A more detailed analysis of genes involved in
      cell wall metabolism, indicated that there was a global decrease in expression of
      genes that promote cell expansion.

PMID- 15448179
TI  - Predicted versus measured photosynthetic water-use efficiency of crop stands
      under dynamically changing field environments.
AB  - Water-use efficiency (WUE) is critical in determining the adaptation and
      productivity of plants in water-limited areas, either under the present climate
      or future global change. Data on WUE are often highly variable and a unifying and
      quantitative approach is needed to analyse and predict WUE for different
      environments. Hsiao has already proposed a set of paradigm equations based on
      leaf gas exchange for this purpose, calculating WUE (ratio of assimilation to
      transpiration) relative to the WUE for a chosen reference situation. This study
      tests the validity and applicability of these equations to cotton and sweet corn
      stands with full canopies in the open field. Measured were evapotranspiration and
      downward flux of atmospheric CO2 into the canopy, soil CO2 efflux, canopy
      temperature, and CO2 and vapour pressure of the air surrounding the canopy. With
      the measured mean WUE and conditions at midday serving as the reference, WUE for
      other times was predicted from the air CO2 and water vapour data, intercellular
      water vapour pressure calculated from canopy temperature, and an assumed ratio of
      Ci/Ca based on leaf gas-exchange data. Provided that the stomatal response to
      humidity as it affected the Ci/Ca ratio was accounted for, the equations
      predicted the moment-by-moment changes in canopy WUE of cotton over daily cycles
      reasonably well, and also the variation in midday WUE from day-to-day over a 47 d
      period. The prediction for sweet corn was fairly good for most parts of the day
      except the early morning. Measurement uncertainties and possible causes of the
      differences between predicted and measured WUE are discussed. Overall, the
      results indicate that the equations may be suitable to simulate changes in WUE
      without upscaling, and also demonstrate clearly the importance of stomatal
      response to humidity in determining stand WUE in the field.

PMID- 15448180
TI  - Nitrate, NO and haemoglobin in plant adaptation to hypoxia: an alternative to
      classic fermentation pathways.
AB  - The role of nitrate reduction to produce nitric oxide (NO) and its subsequent
      oxidation by oxyhaemoglobin as a mechanism to maintain plant cell energetics
      during hypoxia is examined. Nitrate reduction in hypoxic conditions can be
      considered as an alternative respiratory pathway, with nitrate as an intermediate
      electron acceptor, contributing to the oxidation of NADH. NO, produced in the
      reaction, does not accumulate due to the induction of hypoxia-induced (class 1)
      haemoglobins. These haemoglobins remain in the oxyhaemoglobin form, even at
      oxygen tensions two orders of magnitude lower than necessary to saturate
      cytochrome c oxidase. They act, probably in conjunction with a flavoprotein, as
      NO dioxygenases converting NO back to nitrate, consuming NAD(P)H in the process.
      The overall system oxidizes 2.5 moles of NADH per one mole of nitrate recycled
      during the reaction, leading to the maintenance of redox and energy status during
      hypoxia and resulting in the reduced production of ethanol and lactic acid.

PMID- 15448181
TI  - Root growth maintenance during water deficits: physiology to functional genomics.
AB  - Progress in understanding the network of mechanisms involved in maize primary
      root growth maintenance under water deficits is reviewed. These include the
      adjustment of growth zone dimensions, turgor maintenance by osmotic adjustment,
      and enhanced cell wall loosening. The role of the hormone abscisic acid (ABA) in
      maintaining root growth under water deficits is also addressed. The research has
      taken advantage of kinematic analysis, i.e. characterization of spatial and
      temporal patterns of cell expansion within the root growth zone. This approach
      revealed different growth responses to water deficits and ABA deficiency in
      distinct regions of the root tip. In the apical 3 mm region, elongation is
      maintained at well-watered rates under severe water deficit, although only in ABA
      sufficient roots, whereas the region from 3-7 mm from the apex exhibits maximum
      elongation in well-watered roots, but progressive inhibition of elongation in
      roots under water deficit. This knowledge has greatly facilitated discovery of
      the mechanisms involved in regulating the responses. The spatial resolution with
      which this system has been characterized and the physiological knowledge gained
      to date provide a unique and powerful underpinning for functional genomics
      studies. Characterization of water deficit-induced changes in transcript
      populations and cell wall protein profiles within the growth zone of the maize
      primary root is in progress. Initial results from EST and unigene analyses in the
      tips of well-watered and water-stressed roots highlight the strength of the
      kinematic approach to transcript profiling.

PMID- 15448182
TI  - Amplification and assembly of chip-eluted DNA (AACED): a method for high
      throughput gene synthesis.
AB  - A basic problem in gene synthesis is the acquisition of many short
      oligonucleotide sequences needed for the assembly of genes. Photolithographic
      methods for the massively parallel synthesis of high-density oligonucleotide
      arrays provides a potential source, once appropriate methods have been devised
      for their elution in forms suitable for enzyme-catalyzed assembly. Here, we
      describe a method based on the photolithographic synthesis of long (>60mers)
      single-stranded oligonucleotides, using a modified maskless array synthesizer.
      Once the covalent bond between the DNA and the glass surface is cleaved, the full
      length oligonucleotides are selected and amplified using PCR. After cleavage of
      flanking primer sites, a population of unique, internal 40mer dsDNA sequences are
      released and are ready for use in biological applications. Subsequent gene
      assembly experiments using this DNA pool were performed and were successful in
      creating longer DNA fragments. This is the first report demonstrating the use of
      eluted chip oligonucleotides in biological applications such as PCR and assembly
      PCR.

PMID- 15448183
TI  - Lsh, an epigenetic guardian of repetitive elements.
AB  - The genome is burdened with repetitive sequences that are generally embedded in
      silenced chromatin. We have previously demonstrated that Lsh (lymphoid-specific
      helicase) is crucial for the control of heterochromatin at pericentromeric
      regions consisting of satellite repeats. In this study, we searched for
      additional genomic targets of Lsh by examining the effects of Lsh deletion on
      repeat regions and single copy gene sequences. We found that the absence of Lsh
      resulted in an increased association of acetylated histones with repeat sequences
      and transcriptional reactivation of their silenced state. In contrast, selected
      single copy genes displayed no change in histone acetylation levels, and their
      transcriptional rate was indistinguishable compared to Lsh-deficient cells and
      wild-type controls. Microarray analysis of total RNA derived from brain and liver
      tissues revealed that <0.4% of the 15 247 examined loci were abnormally expressed
      in Lsh-/-embryos and almost two-thirds of these deregulated sequences contained
      repeats, mainly retroviral LTR (long terminal repeat) elements. Chromatin
      immunoprecipitation analysis demonstrated a direct interaction of Lsh with
      repetitive sites in the genome. These data suggest that the repetitive sites are
      direct targets of Lsh action and that Lsh plays an important role as 'epigenetic
      guardian' of the genome to protect against deregulation of parasitic retroviral
      elements.

PMID- 15448184
TI  - Comparative analysis of complete genomes reveals gene loss, acquisition and
      acceleration of evolutionary rates in Metazoa, suggests a prevalence of evolution
      via gene acquisition and indicates that the evolutionary rates in animals tend to
      be conserved.
AB  - In this study we systematically examined the differences between the proteomes of
      Metazoa and other eukaryotes. Metazoans (Homo sapiens, Ceanorhabditis elegans and
      Drosophila melanogaster) were compared with a plant (Arabidopsis thaliana), fungi
      (Saccharomyces cerevisiae and Schizosaccaromyces pombe) and Encephalitozoan
      cuniculi. We identified 159 gene families that were probably lost in the Metazoan
      branch and 1263 orthologous families that were specific to Metazoa and were
      likely to have originated in their last common ancestor (LCA). We analyzed the
      evolutionary rates of pan-eukaryotic protein families and identified those with
      higher rates in animals. The acceleration was shown to occur in: (i) the LCA of
      Metazoa or (ii) independently in the Metazoan phyla. A high proportion of the
      accelerated Metazoan protein families was found to participate in translation and
      ribosome biogenesis, particularly mitochondrial. By functional analysis we show
      that no metabolic pathway in animals evolved faster than in other organisms. We
      conclude that evolution in the LCA of Metazoa was extensive and proceeded largely
      by gene duplication and/or invention rather than by modification of extant
      proteins. Finally, we show that the rate of evolution of a gene family in animals
      has a clear, but not absolute, tendency to be conserved.

PMID- 15448185
TI  - Solving the riddle of codon usage preferences: a test for translational
      selection.
AB  - Translational selection is responsible for the unequal usage of synonymous codons
      in protein coding genes in a wide variety of organisms. It is one of the most
      subtle and pervasive forces of molecular evolution, yet, establishing the
      underlying causes for its idiosyncratic behaviour across living kingdoms has
      proven elusive to researchers over the past 20 years. In this study, a
      statistical model for measuring translational selection in any given genome is
      developed, and the test is applied to 126 fully sequenced genomes, ranging from
      archaea to eukaryotes. It is shown that tRNA gene redundancy and genome size are
      interacting forces that ultimately determine the action of translational
      selection, and that an optimal genome size exists for which this kind of
      selection is maximal. Accordingly, genome size also presents upper and lower
      boundaries beyond which selection on codon usage is not possible. We propose a
      model where the coevolution of genome size and tRNA genes explains the observed
      patterns in translational selection in all living organisms. This model finally
      unifies our understanding of codon usage across prokaryotes and eukaryotes.
      Helicobacter pylori, Saccharomyces cerevisiae and Homo sapiens are codon usage
      paradigms that can be better understood under the proposed model.

PMID- 15448186
TI  - HYPROSP: a hybrid protein secondary structure prediction algorithm--a knowledge
      based approach.
AB  - We develop a knowledge-based approach (called PROSP) for protein secondary
      structure prediction. The knowledge base contains small peptide fragments
      together with their secondary structural information. A quantitative measure M,
      called match rate, is defined to measure the amount of structural information
      that a target protein can extract from the knowledge base. Our experimental
      results show that proteins with a higher match rate will likely be predicted more
      accurately based on PROSP. That is, there is roughly a monotone correlation
      between the prediction accuracy and the amount of structure matching with the
      knowledge base. To fully utilize the strength of our knowledge base, a hybrid
      prediction method is proposed as follows: if the match rate of a target protein
      is at least 80%, we use the extracted information to make the prediction;
      otherwise, we adopt a popular machine-learning approach. This comprises our
      hybrid protein structure prediction (HYPROSP) approach. We use the DSSP and EVA
      data as our datasets and PSIPRED as our underlying machine-learning algorithm.
      For target proteins with match rate at least 80%, the average Q3 of PROSP is 3.96
      and 7.2 better than that of PSIPRED on DSSP and EVA data, respectively.

PMID- 15448187
TI  - A comparative method for finding and folding RNA secondary structures within
      protein-coding regions.
AB  - Existing computational methods for RNA secondary-structure prediction tacitly
      assume RNA to only encode functional RNA structures. However, experimental
      studies have revealed that some RNA sequences, e.g. compact viral genomes, can
      simultaneously encode functional RNA structures as well as proteins, and evidence
      is accumulating that this phenomenon may also be found in Eukaryotes. We here
      present the first comparative method, called RNA-DECODER, which explicitly takes
      the known protein-coding context of an RNA-sequence alignment into account in
      order to predict evolutionarily conserved secondary-structure elements, which may
      span both coding and non-coding regions. RNA-DECODER employs a stochastic context
      free grammar together with a set of carefully devised phylogenetic substitution
      models, which can disentangle and evaluate the different kinds of overlapping
      evolutionary constraints which arise. We show that RNA-DECODER's parameters can
      be automatically trained to successfully fold known secondary structures within
      the HCV genome. We scan the genomes of HCV and polio virus for conserved
      secondary-structure elements, and analyze performance as a function of available
      evolutionary information. On known secondary structures, RNA-DECODER shows a
      sensitivity similar to the programs MFOLD, PFOLD and RNAALIFOLD. When scanning
      the entire genomes of HCV and polio virus for structure elements, RNA-DECODER's
      results indicate a markedly higher specificity than MFOLD, PFOLD and RNAALIFOLD.

PMID- 15448188
TI  - Certain 1,4-disubstituted aromatic piperidines and piperazines with extreme
      selectivity for the dopamine D4 receptor interact with a common receptor
      microdomain.
AB  - We previously demonstrated that, in the D4 dopamine receptor, the aromatic
      microdomain that spans the interface of the second and third transmembrane
      segments influences the high-affinity interactions with the D4-selective ligand
      L750,667 [3-[[4-(4-iodophenyl) piperazin-1-yl]methyl]-1H-pyrrolo[2,3-b]pyridine]
      and the D2-selective ligands methylspiperone, aripiprazole, and its congener
      OPC4392 [7-[3-(4-(2,3-dimethylphenyl) piperazinyl) propoxy] 2-(1H)-quinolinone]
      (Schetz et al., 2000). Here we tested a variety of 1,4-disubstituted aromatic
      piperidines/piperazines (1,4-DAPs) with different subtype selectivities and
      functional properties against a panel of D4 receptor mutations in the aromatic
      microdomain to ascertain whether these ligands recognize this common site. Mutant
      D4 receptors were constructed by substituting the nonconserved amino acid(s) from
      the corresponding locations in the D2 receptor. The D4-L2.60W, D4-F2.61V, and D4
      LM3.28-3.29FV substitutions result in alterations of the relative position of
      members of the aromatic microdomain. From these results and molecular models of
      the ligand-receptor complexes, we conclude that 9 of the 11 D4-selective 1,4
      DAPs, including L750,667, have a common pattern of ligand-receptor recognition
      that depends upon favorable interactions with the phenylalanine at position 2.61
      (D4-F2.61V, 20-96-fold decrease). Like methylspiperone, aripiprazole, and
      OPC4392, the two D4-selective 1,4-DAPs that are insensitive to the D4-F2.61V
      mutation are sensitive to aromatics at position 2.60 (D4-L2.60W, 7-20-fold
      increase), and they all have longer spacer arms that permit their tethered
      aromatics to adopt alternative orientations in the binding-site crevice. All 11
      of the D4-selective 1,4-DAPs were sensitive to the D4-LM3.28-3.29FV mutation (13
      494-fold decrease) but not the moderately D2-selective methylspiperone. The
      inferences suggest that subtype selectivity involves two different modes of
      interaction with the microdomain for the D4-selective 1,4-DAPs and a third mode
      for D2-selective 1,4-DAPs.

PMID- 15448189
TI  - Divergent effects of the purinoceptor antagonists suramin and pyridoxal-5'
      phosphate-6-(2'-naphthylazo-6'-nitro-4',8'-disulfonate) (PPNDS) on alpha-amino-3
      hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors.
AB  - Suramin is a large naphthyl-polysulfonate compound that inhibits an array of
      receptors and enzymes, and it has also been reported to block currents mediated
      by glutamate receptors. This study shows that suramin and several structurally
      related compounds [8,8'-[carbonylbis(imino-3,1-phenylenecarbonylamino)]bis-(1,3,5
      naphthalenetrisulfonic acid), 6Na (NF023), 8,8'-(carbonylbis(imino-4,1
      phenylenecarbonylimino-4,1-phenylenecarbonylimino))bis-1,3,5
      naphthalenetrisulfonic acid, Na (NF279), and 4,4',4'',4'''-[carbonyl-bis[imino
      5,1,3-benzenetriyl-bis-(carbonylimino)]]tetrakis-benzene-1,3-disulfonic acid, 8Na
      (NF449)] reduce binding of [3H]alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA) and [3H]fluorowillardiine to rat brain membranes
      and homomeric GluR1-4 receptors, with IC50 values in the range of 5 to 180
      microM. Inhibition often was less than complete at saturating drug concentrations
      and thus seems to be noncompetitive in nature. Pyridoxal-5'-phosphate-6-(2'
      naphthylazo-6'-nitro-4',8'-disulfonate) (PPNDS) is a potent antagonist of
      purinoceptors that shares some structural elements with suramin yet is smaller
      than the latter. PPNDS also had potent effects on AMPA receptors (EC50 value of 4
      microM) but of a kind not seen with the other compounds in that it increased
      binding affinity for radioagonists severalfold. In addition, PPNDS slowed
      association and dissociation rates more than 10 times. In physiological
      experiments with GluR2 receptors, PPNDS at 50 microM reduced the peak current by
      30 to 50% but had only small effects on other waveform aspects such
      desensitization and steady-state currents. This pattern of effects differentiates
      PPNDS from other compounds such as thiocyanate and up-modulators, which increase
      agonist binding by enhancing desensitization or slowing deactivation,
      respectively. Receptor model simulations indicate that most effects can be
      accounted for by assuming that PPNDS slows agonist binding/unbinding and
      stabilizes the bound-closed state of the receptor. By extension, suramin is
      proposed to stabilize the unbound state and thereby to reduce affinity for
      agonists. These drugs thus act through a novel type of noncompetitive antagonism.

PMID- 15448190
TI  - Evidence that mitogen-activated protein kinase phosphatase-1 induction by
      proteasome inhibitors plays an antiapoptotic role.
AB  - Inhibitors of the proteasome, a multicatalytic proteinase complex responsible for
      intracellular proteolysis, activate programmed cell death in part through the c
      Jun-N-terminal kinase (JNK). Proteasome inhibitors also induce mitogen-activated
      protein kinase phosphatase-1 (MKP-1), however, which can inactivate JNK, and we
      therefore considered the hypothesis that MKP-1 induction may be antiapoptotic.
      Over-expression of MKP-1 in A1N4-myc human mammary epithelial and BT-474 breast
      carcinoma cells decreased proteasome inhibitor-mediated apoptosis. On the other
      hand, BT-474 cells stably expressing an MKP-1 small interfering RNA (siMKP-1) and
      MKP-1 knockout mouse embryo fibroblasts underwent enhanced apoptosis compared
      with their respective controls. MKP-1-mediated inhibition of apoptosis was
      associated with decreased phospho-JNK levels, whereas MKP-1 suppression or
      inactivation enhanced phospho-JNK. Anthracyclines repress MKP-1 transcription,
      suggesting that they could enhance proteasome inhibitor-mediated apoptosis. Such
      combinations induced increased cell death in association with enhanced phospho
      JNK and decreased MKP-1 levels. Inhibition of JNK signaling decreased the
      proapoptotic activity of the anthracycline/proteasome inhibitor regimen.
      Xenograft studies showed the combination was more effective at inducing tumor
      growth delay, associated with suppression of MKP-1 and enhancement of apoptosis
      and phospho-JNK. Infection of anthracycline/proteasome inhibitor-treated A1N4-myc
      cells with Adenoviral-MKP-1 suppressed apoptosis and phospho-JNK. Finally, the
      anthracycline/proteasome inhibitor regimen activated apoptosis and phospho-JNK to
      a greater extent in BT-474/siMKP-1 cells than controls. These findings for the
      first time demonstrate that proteasome inhibitor-mediated induction of MKP-1 is
      antiapoptotic through inhibition of JNK. Furthermore, they suggest that a
      proteasome inhibitor/anthracycline regimen holds potential for enhanced antitumor
      activity in part through repression of MKP-1, supporting clinical evaluation of
      such combinations.

PMID- 15448191
TI  - Transcriptional regulation of the human mu-opioid receptor gene by interleukin-6.
AB  - Inflammatory pain is counteracted by a number of physiological processes. For
      example, opioid receptors, which are present on peripheral terminals of sensory
      neurons, are activated by endogenous opioids, which are released from immune
      cells migrating to the inflamed tissue. Earlier data demonstrated that
      interleukin-6 contributes to such inflammation-induced analgesia. In this report,
      we demonstrated that interleukin-6 strongly induces mu-opioid receptor mRNA in
      the human neuroblastoma cell line SH SY5Y, whereas delta-opioid receptor mRNA
      levels are not influenced. The mRNA increase in these cells is followed by an
      increase in mu-opioid receptor-specific binding. Using transcription factor decoy
      oligonucleotides, direct evidence was provided that the up-regulation of mu
      opioid receptor mRNA in intact cells is dependent on the transcription factors
      signal transducers and activators of transcription 1 (STAT1) and STAT3, whereas
      other transcription factors, such as activator protein-1, nuclear factor (NF)
      kappaB, or NF-interleukin-6 are not involved. STAT1 and STAT3 bound to a site
      located at nucleotide -1583 on the promoter of the human mu-opioid receptor gene,
      as shown by transient transfection experiments, electrophoretic mobility shift
      assays, and transcription factor decoy oligonucleotides. A mutation analysis of
      the 5'-TTCATGGAA-3' STAT1/3 element (palindrome underlined) was performed to
      determine nucleotide residues that are necessary for the binding of STAT1 and
      STAT3. It suggested that only the palindromic half sides and the two adjacent
      central nucleotides are required. Neither mutation of the nucleotides outside the
      palindrome nor mutation of the central nucleotide affected STAT1/3 binding.

PMID- 15448192
TI  - The mechanics of surface expansion anisotropy in Medicago truncatula root hairs.
AB  - Wall expansion in tip-growing cells shows variations according to position and
      direction. In Medicago truncatula root hairs, wall expansion exhibits a strong
      meridional gradient with a maximum near the pole of the cell. Root hair cells
      also show a striking expansion anisotropy, i.e. over most of the dome surface the
      rate of circumferential wall expansion exceeds the rate of meridional expansion.
      Concomitant measurements of expansion rates and wall stresses reveal that the
      extensibility of the cell wall must vary abruptly along the meridian of the cell
      to maintain the gradient of wall expansion. To determine the mechanical basis of
      expansion anisotropy, we compared measurements of wall expansion with expansion
      patterns predicted from wall structural models that were either fully isotropic,
      transversely isotropic, or fully anisotropic. Our results indicate that a model
      based on a transversely isotropic wall structure can provide a good fit of the
      data although a fully anisotropic model offers the best fit overall. We discuss
      how such mechanical properties could be controlled at the microstructural level.

PMID- 15448193
TI  - Bacteroid proline catabolism affects N(2) fixation rate of drought-stressed
      soybeans.
AB  - In prior work, we observed that soybean (Glycine max L. cv Merr.) seeds
      inoculated with a mutant Bradyrhizobium japonicum strain unable to catabolize Pro
      (Pro dehydrogenase(-) [ProDH(-)]) resulted in plants that, when forced to depend
      on N(2) fixation as the sole source of nitrogen and subjected to mild drought
      stress, suffered twice as large a loss in seed yield as did plants inoculated
      with the parental strain. Here, we used a continuous gas flow system to measure
      H(2) evolution as a function of time and leaf water potential (Psi(L)). Since one
      H(2) is produced for every N(2) fixed as an obligate part of the mechanism of
      N(2) fixation, these measurements serve as the basis for continuous monitoring of
      the N(2) fixation rate. In five replicate experiments, the slope of the decline
      in N(2) fixation rate in response to water stress was always greater for plants
      inoculated with the mutant strain unable to catabolize Pro or take up H(2)
      (ProDH(-), hup(-)) than it was for plants inoculated with the parental strain
      (ProDH(+), hup(-)). In aggregate, the probability that this difference occurred
      by chance alone was 0.005. In combination with the earlier result, this is
      consistent with bacteroid catabolism of Pro synthesized in response to mild
      drought stress having a positive impact on N(2) fixation rate and seed yield.

PMID- 15448194
TI  - Arsenic hyperaccumulation in gametophytes of Pteris vittata. A new model system
      for analysis of arsenic hyperaccumulation.
AB  - The sporophyte of the fern Pteris vittata is known to hyperaccumulate arsenic
      (As) in its fronds to >1% of its dry weight. Hyperaccumulation of As by plants
      has been identified as a valuable trait for the development of a practical
      phytoremediation processes for removal of this potentially toxic trace element
      from the environment. However, because the sporophyte of P. vittata is a slow
      growing perennial plant, with a large genome and no developed genetics tools, it
      is not ideal for investigations into the basic mechanisms underlying As
      hyperaccumulation in plants. However, like other homosporous ferns, P. vittata
      produces and releases abundant haploid spores from the parent sporophyte plant
      which upon germination develop as free-living, autotrophic haploid gametophyte
      consisting of a small (<1 mm) single-layered sheet of cells. Its small size,
      rapid growth rate, ease of culture, and haploid genome make the gametophyte a
      potentially ideal system for the application of both forward and reverse genetics
      for the study of As hyperaccumulation. Here we report that gametophytes of P.
      vittata hyperaccumulate As in a similar manner to that previously observed in the
      sporophyte. Gametophytes are able to grow normally in medium containing 20 mm
      arsenate and accumulate >2.5% of their dry weight as As. This contrasts with
      gametophytes of the related nonaccumulating fern Ceratopteris richardii, which
      die at even low (0.1 mm) As concentrations. Interestingly, gametophytes of the
      related As accumulator Pityrogramma calomelanos appear to tolerate and accumulate
      As to intermediate levels compared to P. vittata and C. richardii. Analysis of
      gametophyte populations from 40 different P. vittata sporophyte plants collected
      at different sites in Florida also revealed the existence of natural variability
      in As tolerance but not accumulation. Such observations should open the door to
      the application of new and powerful genetic tools for the dissection of the
      molecular mechanisms involved in As hyperaccumulation in P. vittata using
      gametophytes as an easily manipulated model system.

PMID- 15448195
TI  - Starch division and partitioning. A mechanism for granule propagation and
      maintenance in the picophytoplanktonic green alga Ostreococcus tauri.
AB  - Whereas Glc is stored in small-sized hydrosoluble glycogen particles in archaea,
      eubacteria, fungi, and animal cells, photosynthetic eukaryotes have resorted to
      building starch, which is composed of several distinct polysaccharide fractions
      packed into a highly organized semicrystalline granule. In plants, both the
      initiation of polysaccharide synthesis and the nucleation mechanism leading to
      formation of new starch granules are currently not understood. Ostreococcus
      tauri, a unicellular green alga of the Prasinophyceae family, defines the tiniest
      eukaryote with one of the smallest genomes. We show that it accumulates a single
      starch granule at the chloroplast center by using the same pathway as higher
      plants. At the time of plastid division, we observe elongation of the starch and
      division into two daughter structures that are partitioned in each newly formed
      chloroplast. These observations suggest that in this system the information
      required to initiate crystalline polysaccharide growth of a new granule is
      contained within the preexisting polysaccharide structure and the design of the
      plastid division machinery.

PMID- 15448196
TI  - Metabolic profiling of the sink-to-source transition in developing leaves of
      quaking aspen.
AB  - Profiles of small polar metabolites from aspen (Populus tremuloides Michx.)
      leaves spanning the sink-to-source transition zone were compared. Approximately
      25% of 250 to 300 routinely resolved peaks were identified, with carbohydrates,
      organic acids, and amino acids being most abundant. Two-thirds of identified
      metabolites exhibited greater than 4-fold changes in abundance during leaf
      ontogeny. In the context of photosynthetic and respiratory measurements, profile
      data yielded information consistent with expected developmental trends in carbon
      heterotrophic and carbon-autotrophic metabolism. Suc concentration increased
      throughout leaf expansion, while hexose sugar concentrations peaked at mid
      expansion and decreased sharply thereafter. Amino acid contents generally
      decreased during leaf expansion, but an early increase in Phe and a later one in
      Gly and Ser reflected growing commitments to secondary metabolism and
      photorespiration, respectively. The assimilation of nitrate and utilization of
      stored Asn appeared to be marked by sequential changes in malate concentration
      and Asn transaminase activity. Principal component and hierarchical clustering
      analysis facilitated the grouping of cell wall maturation (pectins,
      hemicelluloses, and oxalate) and membrane biogenesis markers in relation to
      developmental changes in carbon and nitrogen assimilation. Metabolite profiling
      will facilitate investigation of nitrogen use and cellular development in Populus
      sp. varying widely in their growth and pattern of carbon allocation during sink
      to-source development and in response to stress.

PMID- 15448197
TI  - Interactions between ethylene and gibberellins in phytochrome-mediated shade
      avoidance responses in tobacco.
AB  - Plants respond to proximate neighbors with a suite of responses that comprise the
      shade avoidance syndrome. These phytochrome-mediated responses include hyponasty
      (i.e. a more vertical orientation of leaves) and enhanced stem and petiole
      elongation. We showed recently that ethylene-insensitive tobacco (Nicotiana
      tabacum) plants (Tetr) have reduced responses to neighbors, showing an important
      role for this gaseous plant hormone in shade avoidance. Here, we investigate
      interactions between phytochrome signaling and ethylene action in shade avoidance
      responses. Furthermore, we investigate if ethylene acts in these responses
      through an interaction with the GA class of hormones. Low red to far-red light
      ratios (R:FR) enhanced ethylene production in wild-type tobacco, resulting in
      shade avoidance responses, whereas ethylene-insensitive plants showed reduced
      shade avoidance responses. Plants with inhibited GA production showed hardly any
      shade avoidance responses at all to either a low R:FR or increased ethylene
      concentrations. Furthermore, low R:FR enhanced the responsiveness of hyponasty
      and stem elongation in both wild-type and Tetr plants to applied GA(3), with the
      stem elongation process being more responsive to GA(3) in the wild type than in
      Tetr. We conclude that phytochrome-mediated shade avoidance responses involve
      ethylene action, at least partly by modulating GA action.

PMID- 15448198
TI  - Heavy metal stress. Activation of distinct mitogen-activated protein kinase
      pathways by copper and cadmium.
AB  - Excessive amounts of heavy metals adversely affect plant growth and development.
      Whereas some regions naturally contain high levels of heavy metals, anthropogenic
      release of heavy metals into the environment continuously increases soil
      contamination. The presence of elevated levels of heavy metal ions triggers a
      wide range of cellular responses including changes in gene expression and
      synthesis of metal-detoxifying peptides. To elucidate signal transduction events
      leading to the cellular response to heavy metal stress we analyzed protein
      phosphorylation induced by elevated levels of copper and cadmium ions as examples
      for heavy metals with different physiochemical properties and functions. Exposure
      of alfalfa (Medicago sativa) seedlings to excess copper or cadmium ions activated
      four distinct mitogen-activated protein kinases (MAPKs): SIMK, MMK2, MMK3, and
      SAMK. Comparison of the kinetics of MAPK activation revealed that SIMK, MMK2,
      MMK3, and SAMK are very rapidly activated by copper ions, while cadmium ions
      induced delayed MAPK activation. In protoplasts, the MAPK kinase SIMKK
      specifically mediated activation of SIMK and SAMK but not of MMK2 and MMK3.
      Moreover, SIMKK only conveyed MAPK activation by CuCl(2) but not by CdCl(2).
      These results suggest that plants respond to heavy metal stress by induction of
      several distinct MAPK pathways and that excess amounts of copper and cadmium ions
      induce different cellular signaling mechanisms in roots.

PMID- 15448199
TI  - Characterization of the silicon uptake system and molecular mapping of the
      silicon transporter gene in rice.
AB  - Rice (Oryza sativa L. cv Oochikara) is a typical silicon-accumulating plant, but
      the mechanism responsible for the high silicon uptake by the roots is poorly
      understood. We characterized the silicon uptake system in rice roots by using a
      low-silicon rice mutant (lsi1) and wild-type rice. A kinetic study showed that
      the concentration of silicon in the root symplastic solution increased with
      increasing silicon concentrations in the external solution but saturated at a
      higher concentration in both lines. There were no differences in the silicon
      concentration of the symplastic solution between the wild-type rice and the
      mutant. The form of soluble silicon in the root, xylem, and leaf identified by
      (29)Si-NMR was also the same in the two lines. However, the concentration of
      silicon in the xylem sap was much higher in the wild type than in the mutant.
      These results indicate that at least two transporters are involved in silicon
      transport from the external solution to the xylem and that the low-silicon rice
      mutant is defective in loading silicon into xylem rather than silicon uptake from
      external solution to cortical cells. To map the responsible gene, we performed a
      bulked segregant analysis by using both microsatellite and expressed sequence tag
      based PCR markers. As a result, the gene was mapped to chromosome 2, flanked by
      microsatellite marker RM5303 and expressed sequence tag-based PCR marker E60168.

PMID- 15448200
TI  - The Arabidopsis phenylalanine insensitive growth mutant exhibits a deregulated
      amino acid metabolism.
AB  - Amino acids and amino acid analogs have been used in numerous genetic screens to
      isolate mutants deficient in amino acid biosynthetic pathways or in the
      regulation of amino acid metabolism. Several of these mutants exhibit relaxed
      feedback control of branched amino acid biosynthetic pathways and are thus
      resistant to accumulation of pathway end products. For example, feedback
      regulated enzymes of the shikimate pathway are anthranilate synthase on the
      branch leading to Trp and chorismate mutase on the branch leading to Phe and Tyr.
      A feedback-insensitive mutant of anthranilate synthase alpha, trp5-1, is
      resistant to toxic Trp analogs. Mutants resistant to Phe have not previously been
      reported, and this article describes the isolation of the recessive Arabidopsis
      Phe insensitive growth mutant pig1-1 by a forward genetic screen. pig1-1 was not
      only tolerant to Phe, Tyr, and Trp, but also to other, not biosynthetically
      related amino acids. Amino acid contents in pig1-1 were significantly elevated
      with respect to wild-type controls but, in contrast to the wild type,
      dramatically decreased when plants were supplemented with 2 mm Phe. Protein
      contents were similar in the mutant and the wild type at all tested conditions.
      Phe catabolism was similar to the wild type in pig1-1 roots but was significantly
      increased in pig1-1 shoots. Phenylalanine uptake into the root, its root-to-shoot
      translocation, and Phe and phenylpropanoid contents were unaltered in pig1-1,
      indicating that pig1-1 is not affected in amino acid translocation or the
      shikimate pathway. Instead, the response of pig1-1 toward amino acid feeding
      indicates that amino acid metabolism is generally deregulated in pig1-1.

PMID- 15448201
TI  - Airborne ethylene may alter antioxidant protection and reduce tolerance of holm
      oak to heat and drought stress.
AB  - Plant-emitted ethylene has received considerable attention as a stress hormone
      and is considered to play a major role at low concentrations in the tolerance of
      several species to biotic and abiotic stresses. However, airborne ethylene at
      high concentrations, such as those found in polluted areas (20-100 nL L(-1)) for
      several days, has received far less attention in studies of plant stress
      tolerance, though it has been shown to alter photosynthesis and reproductive
      stages (seed germination, flowering, and fruit ripening) in some species. To
      assess the potential effects of airborne ethylene on plant stress tolerance in
      polluted areas, the extent of oxidative stress, photo- and antioxidant
      protection, and visual leaf area damage were evaluated in ethylene-treated
      (approximately 100 nL L(-1) in air) and control (without ethylene fumigation)
      holm oak (Quercus ilex) plants exposed to heat stress or to a combination of heat
      and drought stress. Control plants displayed tolerance to temperatures as high as
      50 degrees C, which might be attributed, at least in part, to enhanced
      xanthophyll de-epoxidation and 2-fold increases in alpha-tocopherol, and they
      suffered oxidative stress only when water deficit was superimposed on
      temperatures above 45 degrees C. By contrast, ethylene-treated plants showed
      symptoms of oxidative stress at lower temperatures (35 degrees C) than the
      controls in drought, as indicated by enhanced malondialdehyde levels, lower alpha
      tocopherol and ascorbate concentrations, and a shift of the redox state of
      ascorbate to its oxidized form. In addition, ethylene-treated plants showed
      higher visual leaf area damage and greater reductions in the maximum efficiency
      of the PSII photochemistry than controls in response to heat stress or to a
      combination of heat and drought stress. These results demonstrate for the first
      time that airborne ethylene at concentrations similar to those found in polluted
      areas may reduce plant stress tolerance by altering, among other possible
      mechanisms, antioxidant defenses.

PMID- 15448202
TI  - Local graph alignment and motif search in biological networks.
AB  - Interaction networks are of central importance in postgenomic molecular biology,
      with increasing amounts of data becoming available by high-throughput methods.
      Examples are gene regulatory networks or protein interaction maps. The main
      challenge in the analysis of these data is to read off biological functions from
      the topology of the network. Topological motifs, i.e., patterns occurring
      repeatedly at different positions in the network, have recently been identified
      as basic modules of molecular information processing. In this article, we discuss
      motifs derived from families of mutually similar but not necessarily identical
      patterns. We establish a statistical model for the occurrence of such motifs,
      from which we derive a scoring function for their statistical significance. Based
      on this scoring function, we develop a search algorithm for topological motifs
      called graph alignment, a procedure with some analogies to sequence alignment.
      The algorithm is applied to the gene regulation network of Escherichia coli.

PMID- 15448203
TI  - Terror attacks influence driving behavior in Israel.
AB  - Terror attacks in Israel produce a temporary lull in light accidents followed by
      a 35% spike in fatal accidents on Israeli roads 3 days after the attack. Our
      results are based on time-series analysis of Israeli traffic flows, accidents,
      and terror attacks from January 2001 through June 2002. Whereas prior studies
      have focused on subjective reports of posttraumatic stress, our study shows a
      population-level behavioral response to violent terror attacks.

PMID- 15448204
TI  - Phospholamban structural dynamics in lipid bilayers probed by a spin label
      rigidly coupled to the peptide backbone.
AB  - We have used chemical synthesis and electron paramagnetic resonance to probe the
      structural dynamics of phospholamban (PLB) in lipid bilayers. Derivatives of
      monomeric PLB were synthesized, each of which contained a single spin-labeled
      2,2,6,6,-Tetramethyl-piperidine-N-oxyl-4-amino-4-carboxylic acid amino acid, with
      the nitroxide-containing ring covalently and rigidly attached to the alpha
      carbon, providing direct insight into the conformational dynamics of the peptide
      backbone. 2,2,6,6,-tetramethyl-piperidine-N-oxyl-4-amino-4-carboxylic acid was
      attached at positions 0, 11, and 24 in the cytoplasmic domain or at position 46
      in the transmembrane domain. The electron paramagnetic resonance spectrum of the
      transmembrane domain site (position 46) indicates a single spectral component
      corresponding to strong immobilization of the probe, consistent with the presence
      of a stable and highly ordered transmembrane helix. In contrast, each of the
      three cytoplasmic domain probes has two clearly resolved spectral components
      (conformational states), one of which indicates nearly isotropic nanosecond
      dynamic disorder. For the probe at position 11, an N-terminal lipid anchor shifts
      the equilibrium toward the restricted component, whereas Mg(2+) shifts it in the
      opposite direction. Relaxation enhancement, due to Ni(2+) ions chelated to lipid
      head-groups, provides further information about the membrane topology of PLB,
      allowing us to confirm and refine a structural model based on previous NMR data.
      We conclude that the cytoplasmic domain of PLB is in a dynamic equilibrium
      between an ordered conformation, which is in direct contact with the membrane
      surface, and a dynamically disordered form, which is detached from the membrane
      and poised to interact with its regulatory target.

PMID- 15448205
TI  - PKC412 inhibits the zinc finger 198-fibroblast growth factor receptor 1 fusion
      tyrosine kinase and is active in treatment of stem cell myeloproliferative
      disorder.
AB  - Human stem cell leukemia-lymphoma syndrome usually presents itself as a
      myeloproliferative disorder (MPD) that evolves to acute myeloid leukemia and/or
      lymphoma. The syndrome associated with t(8;13)(p11;q12) results in expression of
      the ZNF198-fibroblast growth factor receptor (FGFR) 1 fusion tyrosine kinase.
      Current empirically derived cytotoxic chemotherapy is inadequate for treatment of
      this disease. We hypothesized that small-molecule inhibitors of the ZNF198-FGFR1
      fusion would have therapeutic efficacy. We characterized the transforming
      activity of ZNF198-FGFR1 in hematopoietic cells in vitro and in vivo. Expression
      of ZNF198-FGFR1 in primary murine hematopoietic cells caused a myeloproliferative
      syndrome in mice that recapitulated the human MPD phenotype. Transformation in
      these assays, and activation of the downstream effector molecules PLC-gamma,
      STAT5, and phosphatidylinositol 3-kinase/AKT, required the proline-rich domains,
      but not the ZNF domains, of ZNF198. A small-molecule tyrosine kinase inhibitor,
      PKC412 (N-benzoyl-staurosporine) effectively inhibited ZNF198-FGFR1 tyrosine
      kinase activity and activation of downstream effector pathways, and inhibited
      proliferation of ZNF198-FGFR1 transformed Ba/F3 cells. Furthermore, treatment
      with PKC412 resulted in statistically significant prolongation of survival in the
      murine model of ZNF198-FGFR1-induced MPD. Based in part on these data, PKC412 was
      administered to a patient with t(8;13)(p11;q12) and was efficacious in treatment
      of progressive myeloproliferative disorder with organomegaly. Therefore, PKC412
      may be a useful therapy for treatment of human stem cell leukemia-lymphoma
      syndrome.

PMID- 15448206
TI  - Evidence for landscape-level, pollen-mediated gene flow from genetically modified
      creeping bentgrass with CP4 EPSPS as a marker.
AB  - Sampling methods and results of a gene flow study are described that will be of
      interest to plant scientists, evolutionary biologists, ecologists, and
      stakeholders assessing the environmental safety of transgenic crops. This study
      documents gene flow on a landscape level from creeping bentgrass (Agrostis
      stolonifera L.), one of the first wind-pollinated, perennial, and highly
      outcrossing transgenic crops being developed for commercial use. Most of the gene
      flow occurred within 2 km in the direction of prevailing winds. The maximal gene
      flow distances observed were 21 km and 14 km in sentinel and resident plants,
      respectively, that were located in primarily nonagronomic habitats. The
      selectable marker used in these studies was the CP4 EPSPS gene derived from
      Agrobacterium spp. strain CP4 that encodes 5-enol-pyruvylshikimate-3-phosphate
      synthase and confers resistance to glyphosate herbicide. Evidence for gene flow
      to 75 of 138 sentinel plants of A. stolonifera and to 29 of 69 resident Agrostis
      plants was based on seedling progeny survival after spraying with glyphosate in
      greenhouse assays and positive TraitChek, PCR, and sequencing results. Additional
      studies are needed to determine whether introgression will occur and whether it
      will affect the ecological fitness of progeny or the structure of plant
      communities in which transgenic progeny may become established.

PMID- 15448207
TI  - Bulk-solvent and hydration-shell fluctuations, similar to alpha- and beta
      fluctuations in glasses, control protein motions and functions.
AB  - The concept that proteins exist in numerous different conformations or
      conformational substates, described by an energy landscape, is now accepted, but
      the dynamics is incompletely explored. We have previously shown that large-scale
      protein motions, such as the exit of a ligand from the protein interior, follow
      the dielectric fluctuations in the bulk solvent. Here, we demonstrate, by using
      mean-square displacements (msd) from Mossbauer and neutron-scattering
      experiments, that fluctuations in the hydration shell control fast fluctuations
      in the protein. We call the first type solvent-slaved or alpha-fluctuations and
      the second type hydration-shell-coupled or beta-fluctuations. Solvent-slaved
      motions are similar to the alpha-fluctuations in glasses. Their temperature
      dependence can be approximated by a Vogel-Tammann-Fulcher relation and they are
      absent in a solid environment. Hydration-shell-coupled fluctuations are similar
      to the beta-relaxation in glasses. They can be approximated by a Ferry or an
      Arrhenius relation, are much reduced or absent in dehydrated proteins, and occur
      in hydrated proteins even if embedded in a solid. They can be responsible for
      internal processes such as the migration of ligands within myoglobin. The
      existence of two functionally important fluctuations in proteins, one slaved to
      bulk motions and the other coupled to hydration-shell fluctuations, implies that
      the environment can control protein functions through different avenues and that
      no real protein transition occurs at approximately 200 K. The large number of
      conformational substates is essential; proteins cannot function without this
      reservoir of entropy, which resides mainly in the hydration shell.

PMID- 15448208
TI  - A poxvirus protein forms a complex with left-handed Z-DNA: crystal structure of a
      Yatapoxvirus Zalpha bound to DNA.
AB  - A conserved feature of poxviruses is a protein, well characterized as E3L in
      vaccinia virus, that confers IFN resistance on the virus. This protein comprises
      two domains, an N-terminal Z-DNA-binding protein domain (Zalpha) and a C-terminal
      double-stranded RNA-binding domain. Both are required for pathogenicity of
      vaccinia virus in mice infected by intracranial injection. Here, we describe the
      crystal structure of the Zalpha domain from the E3L-like protein of Yaba-like
      disease virus, a Yatapoxvirus, in a complex with Z-DNA, solved at a 2.0-A
      resolution. The DNA contacting surface of Yaba-like disease virus Zalpha(E3L)
      closely resembles that of other structurally defined members of the Zalpha
      family, although some variability exists in the beta-hairpin region. In contrast
      to the Z-DNA-contacting surface, the nonbinding surface of members of the Zalpha
      family are unrelated; this surface may effect protein-specific interactions. The
      presence of the conserved and tailored Z-DNA-binding surface, which interacts
      specifically with the zigzag backbone and syn base diagnostic of the Z-form,
      reinforces the importance to poxvirus infection of the ability of this protein to
      recognize the Z-conformation.

PMID- 15448209
TI  - Visual expertise with nonface objects leads to competition with the early
      perceptual processing of faces in the human occipitotemporal cortex.
AB  - Human electrophysiological studies have found that the processing of faces and
      other objects differs reliably at approximately 150 ms after stimulus onset,
      faces giving rise to a larger occipitotemporal field potential on the scalp,
      termed the N170. We hypothesize that visual expertise with nonface objects leads
      to the recruitment of early face-related categorization processes in the
      occipitotemporal cortex, as reflected by the N170. To test this hypothesis, the
      N170 in response to laterally presented faces was measured while subjects
      concurrently viewed centrally presented, novel, nonface objects (asymmetric
      "Greebles"). The task was simply to report the side of the screen on which each
      face was presented. Five subjects were tested during three event-related
      potential sessions interspersed throughout a training protocol during which they
      became experts with Greebles. After expertise training, the N170 in response to
      faces was substantially decreased ( approximately 20% decrease in signal relative
      to that when subjects were novices) when concurrently processing a nonface object
      in the domain of expertise, but not when processing untrained objects of similar
      complexity. Thus, faces and nonface objects in a domain of expertise compete for
      early visual categorization processes in the occipitotemporal cortex.

PMID- 15448210
TI  - Entropy of dialogues creates coherent structures in e-mail traffic.
AB  - We study the dynamic network of e-mail traffic and find that it develops self
      organized coherent structures similar to those appearing in many nonlinear
      dynamic systems. Such structures are uncovered by a general information theoretic
      approach to dynamic networks based on the analysis of synchronization among trios
      of users. In the e-mail network, coherent structures arise from temporal
      correlations when users act in a synchronized manner. These temporally linked
      structures turn out to be functional, goal-oriented aggregates that must react in
      real time to changing objectives and challenges (e.g., committees at a
      university). In contrast, static structures turn out to be related to
      organizational units (e.g., departments).

PMID- 15448211
TI  - Molecular profiling reveals synaptic release machinery in Merkel cells.
AB  - Merkel cell-neurite complexes are somatosensory receptors that initiate the
      perception of gentle touch. The role of epidermal Merkel cells within these
      complexes is disputed. To ask whether Merkel cells are genetically programmed to
      be excitable cells that may participate in touch reception, we purified Merkel
      cells from touch domes and used DNA microarrays to compare gene expression in
      Merkel cells and other epidermal cells. We identified 362 Merkel-cell-enriched
      transcripts, including neuronal transcription factors, presynaptic molecules, and
      ion-channel subunits. Antibody staining of skin sections showed that Merkel cells
      are immunoreactive for presynaptic proteins, including piccolo, Rab3C, vesicular
      glutamate transporter 2, and cholecystokinin 26-33. These data indicate that
      Merkel cells are poised to release glutamate and neuropeptides. Finally, by using
      Ca(2+) imaging, we discovered that Merkel cells have L- and P/Q-type voltage
      gated Ca(2+) channels, which have been shown to trigger vesicle release at
      synapses. These results demonstrate that Merkel cells are excitable cells and
      suggest that they release neurotransmitters to shape touch sensitivity.

PMID- 15448212
TI  - LEAPT: lectin-directed enzyme-activated prodrug therapy.
AB  - Targeted drug delivery to selected sites allows reduced toxicity, enhanced
      efficiency and interchangeable target potential [Langer, R. (2001) Science 293,
      58-59 and Molema, G. & Meijer, D. K. F., eds. (2001) Drug Targeting (Wiley-VCH,
      Weinheim, Germany)]. We describe a bipartite drug-delivery system that exploits
      (I) endogenous carbohydrate-to-lectin binding to localize glycosylated enzyme
      conjugates to specific, predetermined cell types followed by (II) administration
      of a prodrug activated by that predelivered enzyme at the desired site. The
      carbohydrate structure of an alpha-L-rhamnopyranosidase enzyme was specifically
      engineered through enzymatic deglycosylation and chemical reglycosylation.
      Combined in vivo and in vitro techniques (gamma scintigraphy,
      microautoradiography and confocal microscopy) determined organ and cellular
      localization and demonstrated successful activation of alpha-L-rhamnopyranoside
      prodrug. Ligand competition experiments revealed enhanced, specific localization
      by endocytosis and a strongly carbohydrate-dependent, 60-fold increase in
      selectivity toward target cell hepatocytes that generated a >30-fold increase
      (from 0.02 to 0.66 mg) in protein delivered. Furthermore, glycosylation
      engineering enhanced the serum-uptake rate and enzyme stability. This created
      enzyme activity (0.2 units in hepatocytes) for prodrug therapy, the target of
      which was switched simply by sugar-type alteration. The therapeutic effectiveness
      of lectin-directed enzyme-activated prodrug therapy was shown through the
      construction of the prodrug of doxorubicin, Rha-DOX, and its application to
      reduce tumor burden in a hepatocellular carcinoma (HepG2) disease model.

PMID- 15448213
TI  - Anti-BiP antibody levels in juvenile idiopathic arthritis (JIA).

PMID- 15448214
TI  - Copying clinic letters to patients will place additional demands on both
      secondary and primary care: a hospital outpatient questionnaire.

PMID- 15448215
TI  - High-dose intravenous azathioprine pulse treatment in refractory Wegener's
      granulomatosis.

PMID- 15448216
TI  - Haematopoietic stem cell transplantation for refractory Takayasu's arteritis.

PMID- 15448217
TI  - Normalization of anticardiolipin antibodies following rituximab therapy for
      marginal zone lymphoma in a patient with Sjogren's syndrome.

PMID- 15448218
TI  - A case of successful pregnancy in a woman with systemic sclerosis treated with
      cyclosporin.

PMID- 15448219
TI  - The fibromyalgia problem. A Latin American point of view.

PMID- 15448222
TI  - Comment on review on T cells in bone biology.

PMID- 15448223
TI  - Pulmonary function test as screening test for pulmonary artery hypertension in
      scleroderma patients.

PMID- 15448224
TI  - Screening for pulmonary arterial hypertension in systemic sclerosis.

PMID- 15448228
TI  - Science and the Bush Administration.

PMID- 15448229
TI  - Space science. Rising cost of shuttle and Hubble could break NASA budget.

PMID- 15448230
TI  - National Science Foundation. President reverses course, taps Bement as director.

PMID- 15448231
TI  - Paleoanthropology. Oldest human femur wades into controversy.

PMID- 15448232
TI  - Microbiology. Scientist pleads guilty of receiving illegally imported avian flu
      virus.

PMID- 15448233
TI  - DOE labs. Firing draws protest at Los Alamos.

PMID- 15448234
TI  - European patents. Stem cell claims face legal hurdles.

PMID- 15448235
TI  - Settlement of the Pacific: Heaven or hellhole? Islands' destinies were shaped by
      geography.

PMID- 15448236
TI  - Russian science. Academicians react angrily to draft reform plan.

PMID- 15448237
TI  - Vaccines. Rotavirus vaccines' second chance.

PMID- 15448238
TI  - Paleontology. China clamps down on mining to preserve Cambrian site.

PMID- 15448239
TI  - Bioengineering. Biology and the inkjets.

PMID- 15448240
TI  - Climate change. A bit of icy Antarctica is sliding toward the sea.

PMID- 15448241
TI  - AAS High Energy Astrophysics Division meeting: Reconstructing a star's demise,
      bit by exploded bit.

PMID- 15448242
TI  - AAS High Energy Astrophysics Division meeting: X-ray flares size up a neutron
      star.

PMID- 15448243
TI  - AAS High Energy Astrophysics Division meeting. A positron map of the sky.

PMID- 15448244
TI  - AAS High Energy Astrophysics Division meeting: Snapshots from the meeting.

PMID- 15448246
TI  - 2004 Visualization Challenge. Photography.

PMID- 15448247
TI  - 2004 Visualization Challenge. Illustration.

PMID- 15448248
TI  - 2004 Visualization Challenge. Informational graphics.

PMID- 15448249
TI  - 2004 Visualization Challenge. Multimedia--interactive.

PMID- 15448250
TI  - 2004 Visualization Challenge. Multimedia--noninteractive.

PMID- 15448251
TI  - How did the horned lizard get its horns?

PMID- 15448252
TI  - The importance of educating girls.

PMID- 15448253
TI  - Future global warming scenarios, take 2.

PMID- 15448254
TI  - Comment on "Role of NMDA receptor subtypes in governing the direction of
      hippocampal synaptic plasticity".

PMID- 15448256
TI  - Ecology. Globalization, migration, and Latin American ecosystems.

PMID- 15448257
TI  - Geophysics. Silent heralds of megathrust earthquakes?

PMID- 15448258
TI  - Biomedicine. A fresh look at BSE.

PMID- 15448259
TI  - Ecology. Where rivers meet.

PMID- 15448260
TI  - Materials science. Smart biomaterials.

PMID- 15448261
TI  - Self-organized patchiness and catastrophic shifts in ecosystems.
AB  - Unexpected sudden catastrophic shifts may occur in ecosystems, with concomitant
      losses or gains of ecological and economic resources. Such shifts have been
      theoretically attributed to positive feedback and bistability of ecosystem
      states. However, verifications and predictive power with respect to catastrophic
      responses to a changing environment are lacking for spatially extensive
      ecosystems. This situation impedes management and recovery strategies for such
      ecosystems. Here, we review recent studies on various ecosystems that link self
      organized patchiness to catastrophic shifts between ecosystem states.

PMID- 15448262
TI  - A Triassic aquatic protorosaur with an extremely long neck.
AB  - By Middle Triassic time, a number of reptile lineages had diversified in shallow
      epicontinental seas and intraplatform basins along the margins of parts of
      Pangea, including the giraffe-necked protorosaurid reptile Tanystropheus from the
      Western Tethys (Europe and the Middle East), which grew to approximately 5 to 6 m
      long. Here we report another long-necked fossil, Dinocephalosaurus, from
      southwestern China, recently collected in Middle Triassic marine deposits
      approximately 230 million years old. This taxon represents unambiguous evidence
      for a fully aquatic protorosaur. Its extremely elongated neck is explained as an
      adaptation for aquatic life, perhaps for an increase in feeding efficiency.

PMID- 15448263
TI  - Solar wind-induced atmospheric erosion at Mars: first results from ASPERA-3 on
      Mars Express.
AB  - The Analyzer of Space Plasma and Energetic Atoms (ASPERA) on board the Mars
      Express spacecraft found that solar wind plasma and accelerated ionospheric ions
      may be observed all the way down to the Mars Express pericenter of 270 kilometers
      above the dayside planetary surface. This is very deep in the ionosphere,
      implying direct exposure of the martian topside atmosphere to solar wind plasma
      forcing. The low-altitude penetration of solar wind plasma and the energization
      of ionospheric plasma may be due to solar wind irregularities or perturbations,
      to magnetic anomalies at Mars, or both.

PMID- 15448264
TI  - Phytochrome-interacting factor 1 is a critical bHLH regulator of chlorophyll
      biosynthesis.
AB  - Photosynthetic organisms must achieve a delicate balance between the light energy
      absorbed by chlorophyll and their capacity to channel that energy into productive
      photochemical reactions. Release of excess absorbed energy in the cell can cause
      lethal photooxidative damage. We identified a basic helix-loop-helix (bHLH)
      transcription factor, designated PHYTOCHROME-INTERACTING FACTOR 1 (PIF1), that
      negatively regulates chlorophyll biosynthesis. pif1 mutant seedlings accumulate
      excess free protochlorophyllide when grown in the dark, with consequent lethal
      bleaching upon exposure to light. PIF1 interacts specifically with the
      photoactivated conformer of phytochromes A and B, suggesting a signaling pathway
      by which chlorophyll biosynthetic rates are tightly controlled during the
      critical initial emergence of seedlings from subterranean darkness into sunlight.

PMID- 15448265
TI  - Visualization of dislocation dynamics in colloidal crystals.
AB  - The dominant mechanism for creating large irreversible strain in atomic crystals
      is the motion of dislocations, a class of line defects in the crystalline
      lattice. Here we show that the motion of dislocations can also be observed in
      strained colloidal crystals, allowing detailed investigation of their topology
      and propagation. We describe a laser diffraction microscopy setup used to study
      the growth and structure of misfit dislocations in colloidal crystalline films.
      Complementary microscopic information at the single-particle level is obtained
      with a laser scanning confocal microscope. The combination of these two
      techniques enables us to study dislocations over a range of length scales,
      allowing us to determine important parameters of misfit dislocations such as
      critical film thickness, dislocation density, Burgers vector, and lattice
      resistance to dislocation motion. We identify the observed dislocations as
      Shockley partials that bound stacking faults of vanishing energy. Remarkably, we
      find that even on the scale of a few lattice vectors, the dislocation behavior is
      well described by the continuum approach commonly used to describe dislocations
      in atomic crystals.

PMID- 15448266
TI  - Ice flow direction change in interior West Antarctica.
AB  - Upstream of Byrd Station (West Antarctica), ice-penetrating radar data reveal a
      distinctive fold structure within the ice, in which isochronous layers are
      unusually deep. The fold has an axis more than 50 kilometers long, which is
      aligned up to 45 degrees to the ice flow direction. Although explanations for the
      fold's formation under the present flow are problematic, it can be explained if
      flow was parallel to the fold axis approximately 1500 years ago. This flow change
      may be associated with ice stream alterations nearer the margin. If this is true,
      central West Antarctica may respond to future alterations more than previously
      thought.

PMID- 15448267
TI  - Fractionation of the platinum-group elements during mantle melting.
AB  - Experiments in sulfide-silicate systems demonstrate that two sulfide phases are
      stable in the asthenospheric upper mantle: a crystalline osmium-iridium-ruthenium
      enriched monosulfide and a rhodium-platinum-palladium-enriched sulfide melt.
      During silicate melt segregation, monosulfide stays in the solid residue,
      dominating the noble metal spectrum of residual mantle. The sulfide melt is
      entrained as immiscible droplets in the segregating silicate melt, defining the
      noble metal inventory of the basaltic component.

PMID- 15448268
TI  - Distance communication transfer of HIV prevention interventions to service
      providers.
AB  - Most acquired immunodeficiency syndrome (AIDS) service providers are in countries
      with little access to scientific developments relevant to their programs. It is
      critical to transfer advances from the scientific arena to service providers on a
      global scale. Human immunodeficiency virus (HIV) prevention organizations in 78
      countries were randomized to receive either a control condition or a technology
      transfer condition with an interactive distance learning computer training
      curriculum and individualized distance consultation. Of 42 nongovernmental
      organizations in the technology transfer condition, 29 adopted the science-based
      program in their communities or trained other agencies to also use it. Advanced
      communication technologies can create a cost-effective infrastructure to
      disseminate new intervention models to service providers worldwide.

PMID- 15448269
TI  - Avian extinction and mammalian introductions on oceanic islands.
AB  - The arrival of humans on oceanic islands has precipitated a wave of extinctions
      among the islands' native birds. Nevertheless, the magnitude of this extinction
      event varies markedly between avifaunas. We show that the probability that a bird
      species has been extirpated from each of 220 oceanic islands is positively
      correlated with the number of exotic predatory mammal species established on
      those islands after European colonization and that the effect of these predators
      is greater on island endemic species. In contrast, the proportions of currently
      threatened species are independent of the numbers of exotic mammalian predator
      species, suggesting that the principal threat to island birds has changed through
      time as species susceptible to exotic predators have been driven extinct.

PMID- 15448270
TI  - Amazonian ecology: tributaries enhance the diversity of electric fishes.
AB  - Neotropical rivers support a diverse array of endemic taxa, including electric
      fishes of the order Gymnotiformes. A comprehensive survey of the main channels of
      the Amazon River and its major tributaries (>2000-kilometer transect) yielded 43
      electric fish species. Biogeographical analyses suggest that local mainstem
      electric fish diversity is enhanced by tributaries. Mainstem species richness
      tends to increase downstream of tributary confluences, and species composition is
      most similar between tributaries and adjacent downstream mainstem locations.
      These findings support a "nodal" or heterogeneous model of riverine community
      organization across a particularly extensive and diverse geographical region.

PMID- 15448271
TI  - The genomic sequence of the accidental pathogen Legionella pneumophila.
AB  - We present the genomic sequence of Legionella pneumophila, the bacterial agent of
      Legionnaires' disease, a potentially fatal pneumonia acquired from aerosolized
      contaminated fresh water. The genome includes a 45-kilobase pair element that can
      exist in chromosomal and episomal forms, selective expansions of important gene
      families, genes for unexpected metabolic pathways, and previously unknown
      candidate virulence determinants. We highlight the genes that may account for
      Legionella's ability to survive in protozoa, mammalian macrophages, and
      inhospitable environmental niches and that may define new therapeutic targets.

PMID- 15448272
TI  - Nitric oxide represses the Arabidopsis floral transition.
AB  - The correct timing of flowering is essential for plants to maximize reproductive
      success and is controlled by environmental and endogenous signals. We report that
      nitric oxide (NO) repressed the floral transition in Arabidopsis thaliana. Plants
      treated with NO, as well as a mutant overproducing NO (nox1), flowered late,
      whereas a mutant producing less NO (nos1) flowered early. NO suppressed CONSTANS
      and GIGANTEA gene expression and enhanced FLOWERING LOCUS C expression, which
      indicated that NO regulates the photoperiod and autonomous pathways. Because NO
      is induced by environmental stimuli and constitutively produced, it may integrate
      both external and internal cues into the floral decision.

PMID- 15448273
TI  - Recycling endosomes supply AMPA receptors for LTP.
AB  - Long-term potentiation (LTP) of synaptic strength, the most established cellular
      model of information storage in the brain, is expressed by an increase in the
      number of postsynaptic AMPA receptors. However, the source of AMPA receptors
      mobilized during LTP is unknown. We report that AMPA receptors are transported
      from recycling endosomes to the plasma membrane for LTP. Stimuli that triggered
      LTP promoted not only AMPA receptor insertion but also generalized recycling of
      cargo and membrane from endocytic compartments. Thus, recycling endosomes supply
      AMPA receptors for LTP and provide a mechanistic link between synaptic
      potentiation and membrane remodeling during synapse modification.

PMID- 15448274
TI  - A pilot study examining older adults' beliefs related to medication adherence:
      the BERMA survey.
AB  - OBJECTIVE: To establish a multifactorial measure of older adults' beliefs related
      to medication adherence. METHODS: Ninety-two older adults (M = 71.42 years) were
      asked to provide medication and health-related information, memory strategies,
      and complete the Beliefs Related to Medications (BERMA) Survey. RESULTS: The
      final version of the BERMA survey contains 53 questions with three scales. The
      overall reliability of the scale is excellent (Cronbach's alpha =.94), as is the
      reliability of the scales. Correlations show that better rated memory for
      medications was associated with higher reported adherence and fewer external
      memory strategies. Higher perceived ability to deal with health professionals was
      related to higher importance of medication adherence and greater perceived
      seriousness of one's medical condition. Finally, more positive attitudes about
      medications were associated with better self-rated health and fewer side effects.
      DISCUSSION: The results indicate that the BERMA survey is a potentially useful
      research tool for understanding older adults' medication adherence.

PMID- 15448275
TI  - Alcohol, gender, and cognitive performance: a longitudinal study comparing older
      Japanese and non-Hispanic white Americans.
AB  - BACKGROUND: Recent data demonstrate that moderate consumption of alcohol may be
      beneficial to cognition. DESIGN: Longitudinal growth curve analyses controlling
      for variables related to cognition were used to examine the relationship between
      alcohol consumption, ethnic differences, gender, and cognition over a 4-year
      follow-up period. SAMPLE: The sample included 1,836 Japanese American and 2,581
      Non-Hispanic White American community-dwelling adults age 65 and older who were
      cognitively intact at baseline and participated in at least one follow-up
      examination. MEASUREMENT: Cognitive performance was measured using the Cognitive
      Abilities Screening Instrument (CASI) and reaction time. RESULTS: Current
      drinkers scored significantly higher on CASI over time than past drinkers or
      abstainers. The same association between alcohol and CASI was observed in both
      genders and both ethnic groups. CONCLUSION: This study provides support regarding
      the potential beneficial outcomes associated with alcohol consumption and
      cognition and that these benefits were not modified by gender or ethnicity.

PMID- 15448276
TI  - Dementia and depressive symptoms as predictors of home help utilization among the
      oldest old: population-based study in an urban area of Sweden.
AB  - OBJECTIVE: The objective of this article is to investigate predictors of public
      home help utilization, particularly mental health problems such as dementia and
      depressive symptoms. METHODS: A population-based sample of community-dwelling
      people aged 81-100 was interviewed and assessed with medical examinations (N =
      502). RESULTS: Dementia increased the odds of receiving public home help among
      people residing alone. Among coresiding people, it increased the odds of
      receiving home help, but only among those who had extra residential care.
      Depressive symptoms decreased the odds of receiving home help among people with
      lower levels of education who lived alone. Depressive symptoms among highly
      educated people who lived alone and among coresiding people of any educational
      level were not related to receipt of home help. DISCUSSION: Improvement of
      screening activities for public home help needs of community-dwelling elders
      might allow better targeting of limited social resources to the most needy.

PMID- 15448277
TI  - Strategies for enrolling diverse older women in an osteoporosis trial.
AB  - OBJECTIVES: This study reviewed a consumer-oriented process for recruiting
      research volunteers age 65 or older for an osteoporosis clinical trial. METHODS:
      Odds ratios were used to estimate the relative importance of methods to enroll
      research volunteers from three racial or ethnic groups. RESULTS: Nine hundred and
      four women were screened; 168 African American, White, and Hispanic women
      enrolled. Mailings and media were effective when the target population was large
      and knowledgeable about the disease and treatment being investigated. Efficiency
      of mailings was increased when individuals in the mailing list were familiar with
      research and the research center. An interpersonal approach was more effective
      than a media-based approach when the target population was small, unaware of
      their personal risk of the disease, and unfamiliar with research and research
      center. DISCUSSION: Information on the characteristics of potential volunteers
      and their communities will enable readers to evaluate the applicability of
      recruitment methods used.

PMID- 15448278
TI  - Disability symptoms and the price of self-sufficiency.
AB  - OBJECTIVE: Disability symptoms are tiredness, slowness, and pain doing daily
      tasks made difficult by health. The authors study factors that increase and
      decrease disability symptoms, especially effects of equipment and personal
      assistance. METHOD: In National Health Interview Survey Disability Supplement
      Phase 2, people with personal care and household management disabilities were
      asked about fatigue, taking a long time, and pain when doing tasks on their own
      and with assistance. The authors study persons ages 55 and older. RESULTS: Poor
      overall health or disability and severe disability in tasks increase disability
      symptom chances by 11% to 18%. Assistance users are 19% to 20% less likely to
      have symptoms than nonusers. Personal help, alone, or with equipment, relieves
      symptoms better than equipment only, by 9% to 13%. DISCUSSION: Equipment-only
      users are self-sufficient, a highly prized situation. Because they actively
      engage in tasks, symptoms are still likely. This trade-off of psychological gain
      with comfort loss may be preferable to personal help.

PMID- 15448279
TI  - An international perspective on research.

PMID- 15448280
TI  - Herbal product use by African American older women.
AB  - The purposes of this study were to identify patterns of herbal product use for
      health promotion and self-care management among older African American women, to
      explore their use of herbal products to manage disease-specific symptoms, and to
      compare users of herbal products to nonusers. The sample consisted of 57
      community-residing African American women age 65 years and older. Of the sample,
      33% used herbal product(s) within the past year. Those who used herbal products
      perceived their overall health to be better than those who did not use herbal
      products. However, differences in demographic characteristics and locus of
      control between herbal users and nonusers were not significant. More than 40% of
      the herbals used were not discussed with health care providers. Most participants
      using herbals were mixing herbal, prescription, and over-the-counter products.
      Indiscriminate use of herbal products in combination with or in place of
      conventional medicines can be problematic and costly.

PMID- 15448281
TI  - Chronic disease self-management improved with enhanced self-efficacy.
AB  - This pilot study used a quasi-experimental pretest-posttest design to examine if
      participation in a chronic disease self-management program (CDSMP) improved self
      efficacy, self-efficacy health, and self-management behaviors in an underserved,
      poor, rural population. The sample, recruited from two clinics in a south central
      state, consisted of 48 adults (59.70 +/- 11.22 years) and was 79.2% Caucasian (n
      = 38) and 20.8% (n = 10) African American. Trained lay leaders with chronic
      illnesses directed the interactive CDSMP based on Bandura's self-efficacy theory
      that included strategies for personal exercise program development, cognitive
      symptom management, problem solving, and communication skills. Program-specific
      paper-and-pencil instruments were completed prior to and immediately after
      completion of the 6-week program. Significant improvements (p <.10) in self
      efficacy, self-efficacy health, and self-management behaviors occurred. Results
      underscore the need to evaluate intervention programs for specific populations
      and for a new paradigm that focuses on patient-provider partnerships that can
      improve health outcomes in underserved, poor, rural populations.

PMID- 15448282
TI  - A comparative study of variables that have an impact on noncancer end-of-life
      diagnoses.
AB  - By way of analysis of variance, this secondary analysis compared three groups of
      noncancer home hospice patients (AIDS, amyotrophic lateral sclerosis [ALS],and
      other) for psychological correlates of adaptation and well-being, pain, and
      physical function, as measured by the Life Closure Scale (LCS), the Affect
      Balance Scale, the McGill-Melzack Pain Questionnaire Part I, and the Karnofsky
      Performance Status Scale. The sample included 10 AIDS patients (Group 1), 6 ALS
      patients (Group 2), and 5 patients with other noncancer, end-stage diseases
      (Group 3). A significant difference was found between Group 2 (ALS) and Group 3
      (other) on the LCS, F(2, 18) = 4.3, p =.03. Scheffe and Duncan range post hoc
      tests and at test at the p</=.05 level (t9 = 4.1, p =.003) confirmed the finding.
      No significant group differences were found among the ALS, AIDS, and other groups
      in measures of psychological well-being, pain, and physical function.

PMID- 15448283
TI  - A voice for the dying.
AB  - Secondary analysis of data collected for a grounded theory study of family
      surrogate decision-making processes at the end of life was undertaken to describe
      participants' perceptions of the needs of family decision makers as expressed
      through their advice to others. Data were analyzed using the constant comparative
      method of grounded theory, resulting in identification of the major categories
      and their properties describing surrogates' recommendations. The entire data set
      (approximately 22 hours of audiotaped narrative data collected from persons who
      had functioned as surrogates during the terminal phase of a family member's
      cancer) was newly analyzed for the secondary analysis. All participants
      experienced the role as very demanding. Those who were able to see that another's
      wishes were honored experienced satisfaction. Advice from experienced surrogates
      offers nurses both direct guidance to help them meet surrogates' needs and
      insight to assist them in coaching surrogates in the performance of this critical
      role.

PMID- 15448284
TI  - Approaches to improving recruitment and retention of minority elders
      participating in research: examples from selected research groups including the
      National Institute on Aging's Resource Centers for Minority Aging Research.
AB  - This introductory overview addresses the importance of recruiting and retaining
      racial and ethnic minority elders in biopsychosocial research. It highlights
      developments by scholars, many associated with the National Institute on Aging's
      Resource Centers for Minority Aging Research, to develop and reinforce a research
      infrastructure intended to minimize the minority/nonminority differential in
      health and its social sequelae for older people.

PMID- 15448285
TI  - Involving rural, older African Americans and their female informal caregivers in
      research.
AB  - OBJECTIVE: This article presents the methodology, procedures, and results for
      involving rural, older African Americans and recruiting their female informal
      caregivers for a well-being and service use study. METHODS: Using a list of 1,994
      Medicare enrollees, this study adapted a reversed screening telephone methodology
      tested on urban African American elders and their caregivers. It used trained
      screeners, local African American female interviewers, and a mixed-mode procedure
      (i.e., telephone and canvassing) to screen elders and recruit caregivers.
      RESULTS: Adequate information for 1,547 listings allowed screeners to contact
      qualified elders meeting the study criteria. Using chi-square analysis,
      significant differences were found between telephone and canvassing screening
      methods on nonreferral cases and referral cases. Elders or a proxy referred 286
      caregivers. Interviewers obtained 265 of 300 proposed caregiver interviews.
      DISCUSSION: Knowledge about the involvement of rural, older African Americans and
      recruitment of their female informal caregivers in research is essential to
      understanding recruitment successes and pitfalls in ethnic minority research.

PMID- 15448286
TI  - Design of a case management approach to enhance cancer screening trial retention
      among older African American men.
AB  - PURPOSE: The purpose of this study was to enhance retention among African
      American men enrolled in a cancer screening trial. DESIGN: A telephone-based,
      randomized trial design was used. The intervention group included 352 African
      American men aged 55+. Case managers contacted participants at least monthly and
      provided information and referral services to participants and their relatives.
      RESULTS: The mean age of participants was 65.7 years. A total of 14,978 calls
      were made resulting in 780 referrals. The 10 most frequent referrals were for
      scheduling medical appointments, health information, insurance information, legal
      aid, transportation, cancer screening information, information
      technology/computer information, employment, housekeeping/chore services, and
      food programs. CONCLUSIONS: The case managers served as links between
      participants and community-based resources. The types of referrals made could be
      associated with the age-related needs of the participants.

PMID- 15448287
TI  - Access, relevance, and control in the research process: lessons from Indian
      country.
AB  - OBJECTIVE: To illustrate successful strategies in working with American Indian
      (AI) and Alaska Native (AN) communities in aging and health research by
      emphasizing access, local relevance, and decision-making processes. METHODS: Case
      examples of health studies involving older AIs (greater than or equal to 50
      years) among Eastern Band Cherokee Indians, a federally recognized reservation;
      the Cherokee Nation, a rural, nonreservation, tribal jurisdictional service area;
      and Lakota tribal members living in Rapid City, South Dakota. RESULTS: Local
      review and decision making reflect the unique legal and historical factors
      underpinning AI sovereignty. Although specific approval procedures vary, there
      are common expectations across these communities that can be anticipated in
      conceptualizing, designing, and implementing health research among native elders.
      CONCLUSIONS: Most investigators are unprepared to address the demands of health
      research in AI communities. Community-based participatory research in this
      setting conflicts with investigators' desire for academic freedom and scientific
      independence. Successful collaboration promises to enhance research efficiencies
      and move findings more quickly to clinical practice.

PMID- 15448288
TI  - Normative health research experiences among African American elders.
AB  - OBJECTIVE: Data are meager regarding the prevalence of participation and the
      overall experience of African American elders in research across a variety of
      health-related studies. This study sought to increase our knowledge about older
      African Americans' participation in health research by capturing some of their
      normative experiences and attitudes. METHODS: A telephone-based survey was
      conducted on 1,290 urban African Americans greater than or equal to 60 years old.
      The assessment focused on issues of housing, neighborhoods, health, and
      experiences with health research. RESULTS: The overall prevalence of respondents
      who took part in a health research project was 14%. Significant predictors
      included income, attitudes about fairness, perceptions of protection from harm,
      understanding of research as a key to improving health care, and participation in
      survey research. DISCUSSION: Findings underscore the importance of addressing
      economic, educational, and trust barriers to research participation as well as
      the importance of conveying a sense of caring for the health of individuals and
      the community as a whole.

PMID- 15448289
TI  - Ethnic minority older adults participating in clinical research: developing
      trust.
AB  - OBJECTIVE: African American, Latino, and American Indian older adults are
      underrepresented in clinical research studies. A significant barrier to
      participation in research is mistrust of the scientific community and
      institutions. The aims of this article are to discuss the lack of representation
      of ethnic minorities in clinical research. METHODS: This article presents a
      review of the literature regarding medical research mistrust. Also described are
      the trust-building activities of the Resource Centers on Minority Aging Research
      (RCMAR), federally funded centers focused on research and aging in communities of
      color. DISCUSSION: The RCMAR centers are building trust with the communities they
      serve, resulting in the recruitment and retention of ethnic minority older adults
      in clinical research studies and health promotion projects. Implications are
      discussed for other researchers toward building trust with ethnic minority elders
      to increase their participation in research.

PMID- 15448290
TI  - The effectiveness of an advance notice letter on the recruitment of African
      Americans and Whites for a mailed patient satisfaction survey.
AB  - OBJECTIVE: Evaluate an advance notice letter for enhancing patient satisfaction
      survey response rates in African Americans and Whites. METHODS: Randomized trial
      of an advance notice letter (versus no letter) mailed two weeks prior to a mail
      satisfaction survey in a random sample of 600 African American and White patients
      ages 50 and older, stratified by ethnicity, sex, and age. RESULTS: The advance
      letter was independently associated with a completed survey in Whites (odds ratio
      = 2.73; 95% confidence interval [CI] 1.66, 4.50), but not in African Americans
      (odds ratio = 1.24; 95% CI 0.76, 2.02). Being male was independently associated
      with returning a survey in Whites (odds ratio = 1.86; 95% CI 1.13, 3.06). Younger
      age (odds ratio = 0.98; 95% CI 0.96, 0.99) was independently associated with a
      completed survey in African Americans. DISCUSSION: An advance letter prior to a
      satisfaction survey is associated with increased response rates in Whites, but
      not in African Americans.

PMID- 15448291
TI  - Recruitment and retention strategies for longitudinal African American caregiving
      research: the Family Caregiving Project.
AB  - OBJECTIVE: This article provides a detailed discussion, guided by a culturally
      competent approach, on recruitment and retention strategies used to study
      caregiving to older dependent elders in African American families. METHODS: The
      study (lasting from 1995 through 2000) included collecting three waves of data, 9
      months apart, among 202 caregiving units (containing a maximum of three
      caregivers per unit). RESULTS: Four key strategies were identified as useful in
      recruiting and retaining the sample: (a) assigning the same interviewers to
      communicate with and interview study participants for each wave of data
      collection, (b) ensuring that all interviewers are knowledgeable of possible
      family dynamics and social issues within the African American community (e.g.,
      access to health care, income and education issues, and discrimination), (c)
      providing a mechanism by way of a toll-free number for all participants to
      contact the project staff at the participant's convenience, and (d) allowing
      flexibility in scheduling and rescheduling interviews at the participant's
      convenience. DISCUSSION: Researchers need to acquire knowledge and develop skills
      that will foster culturally competent approaches when studying diverse cultural
      groups, which involves incorporating the beliefs, values, and attitudes of a
      cultural group in every phase of the research project, from conceptualization to
      interpretation of findings. Additionally, a genuine interest in, knowledge of,
      and respect for the population are necessary to help improve participant
      involvement in longitudinal research among African American caregivers.

PMID- 15448292
TI  - Social marketing as a framework for recruitment: illustrations from the REACH
      study.
AB  - OBJECTIVE: Recruitment is often the most challenging aspect of research with
      older persons. Social marketing--applying marketing techniques to influence the
      behavior of target audiences to improve their welfare--can help researchers
      identify factors that influence recruitment. METHODS: Illustrations of social
      marketing principles are provided from the Resources for Enhancing Alzheimer's
      Caregiver Health project, a national Alzheimer's caregivers study that targeted
      ethnic and racial minorities. RESULTS: Social marketing principles--the six Ps of
      participants, product, price, place, promotion, and partners--provide a
      theoretical framework for organizing and planning recruitment activities,
      including developing varying strategies to define the target audience
      (participants), develop the intervention (product), manage time and trouble
      (price), target the audience, improve accessibility (place), promote the study,
      and develop and work with partners. DISCUSSION: Strategies to enhance recruitment
      are often undertaken without a comprehensive plan. A social marketing plan
      provides a framework to map out the steps in recruitment that will be needed and
      to plan for allocations of time, staff, and resources.

PMID- 15448293
TI  - Fair and fast reviews.

PMID- 15448294
TI  - Coping with trauma and hardship among unaccompanied refugee youths from Sudan.
AB  - The purpose of this study was to explore how unaccompanied refugee youths from
      Sudan, who grew up amid violence and loss, coped with trauma and hardship in
      their lives. The author used a case-centered, comparative, narrative approach to
      analyze the narratives of 14 male unaccompanied refugee youths from Sudan
      recently resettled in the United States. She analyzed narratives for both content
      and form and identified four themes that reflect coping strategies used by the
      participants: (a) collectivity and the communal self, (b) suppression and
      distraction, (c) making meaning, and (d) emerging from hopelessness to hope. The
      findings underscore the importance of understanding the cultural variations in
      responses to trauma and are discussed in relation to the concept of resilience.

PMID- 15448295
TI  - Infant-feeding beliefs and experiences of Black women enrolled in WIC in the New
      York metropolitan area.
AB  - In this ethnographic inquiry, the author explored infant-feeding beliefs and
      experiences of Black women enrolled in WIC (BWEW) in a New York metropolitan
      inner city. The study was conducted over an 18-month period and included 319
      people (130 BWEW, 116 children, 20 grandmothers, 17 fathers, 11 friends, and 25
      other relatives). From this group of BWEW, the author interviewed and observed 11
      primiparous key informants during pregnancy and the first year postpartum to see
      how infant-feeding decisions fit into the context of their everyday lives. The
      major themes that emerged from analysis include (a) formula-feeding experiences
      were the norm for most BWEW, (b) life experiences of BWEW included a
      preponderance of loss and stress, and (c) infant-feeding beliefs of BWEW
      reflected responses to life experiences. These findings could be used to provide
      culturally sensitive care for BWEW.

PMID- 15448296
TI  - Modes of entry into services for young children with disruptive behaviors.
AB  - The authors undertook this study to describe Latina mothers' professional help
      seeking for their young children's disruptive behaviors. They interviewed 62
      Cuban, Puerto Rican, and Dominican first-time help seekers and found four modes
      of entry: (a) coercion, (b) acceptance of offered referral, (c) responsive and
      resourceful help seeking subsequent to school reports of behavior problems, and
      (d) a laborious and convoluted path that was characteristic of 52% of the sample.
      Schools, maternal and child characteristics, and social network forces played
      significant roles for all mothers, but the final determinants of service entry
      varied by the mode of entry followed. Findings suggest that problem labeling is
      not a necessary precursor to service entry and that direct referrals might
      effectively shortcut the help-seeking process. Finally, the process that
      underlies service entry would be described more aptly as a Theory of Affective
      Action than a Theory of Reasoned Action.

PMID- 15448297
TI  - "Being in a funk": teens' efforts to understand their depressive experiences.
AB  - Although there is literature about adults' experiences of depression, little
      research has focused on teenagers' experiences. In this article, the authors
      describe how a sample of adolescents makes sense of depression and responds to a
      depression diagnosis. Twenty-two adolescents participated in in-depth individual
      or focus group interviews. Teens discussed their experiences with depression and
      getting health care for depression, and described a trajectory similar to that
      found among adults: a slow growth of distress, a time of being in a funk, and a
      time of consideration of whether they are depressed. Teens who received a
      diagnosis from a medical provider then sought to make sense of their depression.
      Teens understood a depression diagnosis as a helpful label, a chronic medical
      problem, or a significant part of their identity. Understanding the subjective
      experience of adolescents who are depressed might increase health care
      providers'empathy and improve their communication with teens.

PMID- 15448298
TI  - Illness experiences of homeless youth.
AB  - The purpose of this study was to document the illness experiences of homeless
      youth. The research was a focused ethnography with 45 clinic- and street-based
      homeless youth aged 15 to 23 years. The authors noted gender differences for
      health-seeking behaviors, with most male youth reporting embarrassment about
      needing to seek care, and female youth reporting fears over safety issues while
      ill and homeless. Most youth under age 18 stated that they were often denied
      health care at hospitals because of their underage status, and youth over age 18
      stated that health care bills contributed to their inability to obtain stable
      housing. Street-based youth reported more illnesses related to substance use and
      greater reliance on emergency departments for health care than clinic-based youth
      did. Policies and programs focused on improving the health of homeless youth need
      to address the differences in illness experiences by age, gender, and sampling
      site.

PMID- 15448299
TI  - Practices that facilitate critically burned children's holistic healing.
AB  - Advances in medical technology have enabled many children to survive injuries
      that less than 10 years ago would have caused death. The intense physical care
      and the children's and families' emotional needs place extraordinary demands on
      pediatric burn nurses. In this article, the author reports the findings of an
      interpretive study that examined the experiences of 16 pediatric burn intensive
      care unit nurses for the purpose of uncovering and articulating practices that
      help critically burned children to heal holistically. Following 112 hours of
      interviews and 134 hours of observing the nurses while they worked, she
      identified 12 practices and aggregated them into the theme Healing the Child
      Within. She observed the nurses laughing, playing, singing, talking, and praying
      with the children. These everyday practices were for the sake of maintaining or
      reestablishing harmony of the children's mind, body, and spirit.

PMID- 15448300
TI  - Crossing the line: adolescents' experiences of controlling their tobacco use.
AB  - Although adolescents are often curious about cigarettes and anxious to "try"
      smoking, they are unsure about what engaging in the act of smoking will mean.
      Most adolescents who experiment with smoking do not set out to become addicted to
      tobacco. Using a grounded theory approach, the authors examined the process youth
      undergo to regain control over their smoking. Accounts of early smoking
      experiences suggest that youth undergo a process to control tobacco use that
      includes (a) determining if smoking is a problem, (b) "crossing the line" of
      acceptable tobacco use, and (c) implementing strategies to regain control of
      smoking. The findings of this study lay the basis for the development of harm
      reduction approaches that facilitate youth's propensity to control their tobacco
      use.

PMID- 15448301
TI  - Adolescent girls' perspectives of family interactions related to menarche and
      sexual health.
AB  - In this study, the author explores what girls learn at menarche from family about
      acknowledging and accepting positive feelings in relation to their bodies and
      about making active decisions regarding their bodies and potential sexual
      practices. The author conducted in-depth individual interviews with 22 African
      American, European American, and multiethnic girls, aged 14 to 18 years, from
      both high- and low-income families. She employed an interpretive methodological
      approach using narrative analysis. The results of this study revealed that girls
      who were prepared for the physical changes at menarche were better able to
      acknowledge and accept this bodily change. Also, when girls'wider potentials,
      such as intellectual or creative capacities, were recognized, they were more
      likely to describe pleasurable aspects associated with this transition. In
      contrast, when sex and reproduction were referenced, girls were more likely to
      associate fear, shame, dysfunction, and victimization with their bodies.

PMID- 15448302
TI  - Conducting life history research with adolescents.
AB  - This article is a commentary on the life history approach, which specifically
      described aspects of and offered suggestions for conducting life history research
      with adolescents. The life history approach is well suited to a wide variety of
      types of health-related inquiry. In this article, the author used an exemplar
      study to show how well the life history approach was suited for questions
      regarding adolescent issues. This approach was also a good match for the
      developmental skills and needs of adolescents. The author uses the strengths and
      weaknesses of the approach and a detailed example of how she used the life
      history data to identify themes drawn from the exemplar study. She makes specific
      suggestions, including the development and implementation of an interview guide,
      planning and scheduling interviews, and the use of a life history grid. She
      includes examples of each suggestion and a sample life history grid.

PMID- 15448303
TI  - Emotional responses to sexual and emotional infidelity: constants and differences
      across genders, samples, and methods.
AB  - In three studies (total N = 619), the authors tested an evolutionary hypothesis:
      Men are more bothered by sexual than emotional infidelity, whereas the reverse is
      true of women. More diverse samples (in age) and measures than is typical were
      used. In Study 1, the authors found across gender, sample, and method that sexual
      infidelity was associated with anger and blame, but emotional infidelity was
      associated with hurt feelings. The evolutionary effect was replicated with
      undergraduates but not with the nonstudent sample. In Study 2, narrative
      scenarios were used; it was found that nonstudent men and women were more hurt
      and upset by emotional infidelity but were made angrier by sexual infidelity. In
      Study 3, using Likert-type scales, scenarios, and a nonstudent sample, it was
      found that both genders were more upset, hurt, and angrier about sexual than
      emotional transgressions when rating one kind without hearing the opposite type.
      The implications for how emotional responses evolved are discussed.

PMID- 15448304
TI  - Close relationships and the working self-concept: implicit and explicit effects
      of priming attachment on agency and communion.
AB  - Two studies investigated how contextually activating attachment relationships
      influences the working self-concept in terms of agency and communion. In Study 1,
      245 participants were primed with a secure, avoidant, or anxious-ambivalent
      relationship and the implicit accessibility of agency and communion was assessed
      using word fragments. Activating a secure relationship increased the
      accessibility of communion, whereas activating an anxious-ambivalent relationship
      increased the accessibility of agency. In Study 2, 123 participants were primed
      with a secure, preoccupied, avoidant-dismissive, or avoidant-fearful relationship
      and explicit self-perceptions of agency and communion traits were assessed using
      the Extended Personality Attributes Questionnaire (EPAQ). Gender interacted with
      the attachment prime, such that men primed with a secure relationship reported
      higher communion than did men primed with an avoidant (dismissive or fearful)
      relationship, whereas women primed with an anxious (preoccupied or fearful)
      relationship reported higher agency than did women primed with a secure
      relationship.

PMID- 15448305
TI  - Personality characteristics associated with romantic attachment: a comparison of
      interview and self-report methodologies.
AB  - This study compared the personality attributes associated with self-report versus
      interview assessment of romantic attachment. Twenty-three-year-olds (N = 83)
      completed the Romantic Attachment Interview, the Experiences in Close
      Relationship Inventory, and measures of response bias, self-enhancement, and self
      insight. Five psychologists evaluated the participants' personality. Although
      both self-report and interview assessment were related to attachment-relevant
      personality attributes, interview assessment was slightly more likely to explain
      unique variance in personality, especially regarding intrapsychic attributes.
      Self-enhancement was negatively related to secure attachment and positively
      related to dismissing attachment. The opposite pattern emerged for self-insight.
      A subgroup of 12 vulnerable individuals who described themselves as securely
      attached on self-report was judged as dismissing according to interview
      assessment. These individuals scored low on self-insight and high on self
      enhancement and psychological vulnerability. The results are discussed with
      reference to the relative strengths of different measures of romantic attachment
      and relations among dismissing attachment, self-enhancement, and narcissism.

PMID- 15448306
TI  - Dialectical self-esteem and East-West differences in psychological well-being.
AB  - A well-documented finding in the literature is that members of many East Asian
      cultures report lower self-esteem and psychological well-being than do members of
      Western cultures. The authors present the results of four studies that examined
      cultural differences in reasoning about psychological contradiction and the
      effects of naive dialecticism on self-evaluations and psychological adjustment.
      Mainland Chinese and Asian Americans exhibited greater "ambivalence" or
      evaluative contradiction in their self-attitudes than did Western synthesis
      oriented cultures on a traditional self-report measure of self-esteem (Study 1)
      and in their spontaneous self-descriptions (Study 2). Naive dialecticism, as
      assessed with the Dialectical Self Scale, mediated the observed cultural
      differences in self-esteem and well-being (Study 3). In Study 4, the authors
      primed naive dialecticism and found that increased dialecticism was related to
      decreased psychological adjustment. Implications for the conceptualization and
      measurement of self-esteem and psychological well-being across cultures are
      discussed.

PMID- 15448307
TI  - The backlash of token mobility: the impact of past group experiences on
      individual ambition and effort.
AB  - Two studies investigated the impact of past ingroup experiences on individual
      aspirations and effort. Participants were told that in the past, members of their
      group had either been offered no opportunities (closed), few opportunities
      (token), or equal opportunities (open) to achieve a desired outcome. The results
      show that past group experiences determine responses to current opportunities and
      affect the perceived feasibility of individual success as well as individual
      performance. Exposure to a token system has different effects, depending on
      whether the group is historically advantaged or disadvantaged. Whereas those with
      a collective history of success see token mobility as a challenge and show
      superior performance, the same situation constitutes a threat to members of a
      historically disadvantaged group, who fail to take advantage of the opportunities
      offered to them and perform suboptimally.

PMID- 15448308
TI  - Resistance to persuasion and attitude certainty: the moderating role of
      elaboration.
AB  - Recent research has demonstrated that when people resist persuasive attacks, they
      can under specifiable conditions become more certain of their initial attitudes.
      The present research explores the role of elaboration in determining when this
      effect will occur. Using both self-reported differences in situational
      elaboration (Study 1) and chronic individual differences in the need for
      cognition (Study 2), it is demonstrated that resisting persuasion increases
      attitude certainty primarily when elaboration is high. When elaboration is low,
      resisting persuasion does not appear to impact attitude certainty. These findings
      shed light on the role of metacognitive factors in resistance to persuasion,
      pinpointing the conditions under which these factors come into play.

PMID- 15448309
TI  - Responses to interracial interactions over time.
AB  - The current work tested and expanded on Plant and Devine's (2003) model of the
      antecedents and implications of interracial anxiety by examining people's
      experiences with interracial interactions at two time points. Study 1 explored
      non-Black people's responses to interactions with Black people and Study 2
      explored Black people's responses to interactions with White people. Non-Black
      participants' expectancies about coming across as biased in interracial
      interactions and Black participants' expectancies about White people's bias
      predicted their interracial anxiety and whether they had positive interactions
      with outgroup members during the 2 weeks between assessments. Across both
      studies, interracial anxiety predicted the desire to avoid interactions with
      outgroup members. In addition, participants who were personally motivated to
      respond without prejudice reported more positive expectancies. The findings are
      discussed in terms of the implications for understanding the course and quality
      of interracial interactions.

PMID- 15448310
TI  - Watch out! That could be dangerous: valence-arousal interactions in evaluative
      processing.
AB  - Seven studies involving 146 undergraduates examined the effects of stimulus
      valence and arousal on direct and indirect measures of evaluative processing.
      Stimuli were emotional slides (Studies 1 to 6) or words (Study 7) that
      systematically varied in valence and arousal. Evaluative categorization was
      measured by reaction times to evaluate the stimuli (Studies 2, 3, and 7),
      latencies related to emotional feelings (Study 3), and incidental effects on
      motor performance (Studies 4 and 5). A consistent interaction was observed such
      that evaluation latencies were faster if a negative stimulus was high in arousal
      or if a positive stimulus was low in arousal. Studies 1, 6, and 7 establish that
      the findings are not due to stimulus identification processes. The findings
      therefore suggest that people make evaluative inferences on the basis of stimulus
      arousal.

PMID- 15448311
TI  - Less thought, more punishment: need for cognition predicts support for punitive
      responses to crime.
AB  - Three studies examined the relationship between need for cognition and support
      for punitive responses to crime. The results of Study 1 (N = 110) indicated that
      individuals high in need for cognition were less supportive of punitive measures
      than their low need for cognition counterparts. This finding was replicated in
      Study 2 (N = 1,807), which employed a nationally representative probability
      sample and included a more extensive battery of control variables. The purpose of
      Study 3 (N = 255) was to identify a third variable that might explain this
      relationship. This final study's results suggest that attributional complexity
      mediates the relationship between need for cognition and punitiveness. High need
      for cognition individuals are less supportive of punitive measures because they
      endorse more complex attributions for human behavior than their low need for
      cognition peers.

PMID- 15448312
TI  - The causal role of theories of relationships: consequences for satisfaction and
      cognitive strategies.
AB  - Two studies demonstrated the causal role of relationship theories in influencing
      relationship satisfaction and the processes affecting satisfaction. In both
      studies, participants were induced to hold either the soulmate or work-it-out
      theory. Feelings that one's partner was ideal (or not) were associated with
      relationship satisfaction more strongly for people induced to hold the soulmate
      theory than the work-it-out theory (Study 1). In Study 2, participants' beliefs
      about their relationships were threatened, and strategies for responding to this
      threat were assessed. Inducing people to hold the soulmate theory resulted in
      more relationship-enhancing cognitions if participants believed they were with
      the right person but more relationship-detracting cognitions if participants did
      not believe they were with the right person. These polarizing tendencies were
      enhanced under threat. In contrast, inducing people to hold a work-it-out theory
      produced almost no biased processing, leading people to process information
      similarly, regardless of their feelings about their partner.

PMID- 15448313
TI  - Proceedings of the Compact Ultrasound Conference sponsored by the American
      Institute of ultrasound in medicine.

PMID- 15448314
TI  - History of ophthalmic ultrasound.

PMID- 15448315
TI  - The mammary hamartoma: appreciation of additional imaging characteristics.
AB  - OBJECTIVE: To determine the mammographic and sonographic findings of hamartomas
      that were not classic on imaging, how pathologists distinguish the hamartoma from
      benign breast tissue on core samples, and reasons for discrepancies between core
      and surgical biopsy. METHODS: A retrospective review of all image-recommended
      core biopsies between 1993 and 2001 was performed. There were 41 cases of
      hamartomas found on either core or surgical biopsy. The mammographic,
      sonographic, and pathologic findings were reviewed. RESULTS: Of 41 hamartomas in
      38 patients, 18 went on to surgical biopsy. Of these 18 cases, 4 cases of
      hamartoma on core biopsy were fibroadenoma after excision; 2 cases of hamartoma
      on core biopsy were confirmed by surgery; and 12 cases of fibrocystic change
      after core biopsy were hamartoma after surgical biopsy. The 4 cases of
      fibroadenoma shown at final pathologic examination were excluded from imaging
      review, leaving 37 cases. In the 20 patients who underwent only core sampling, 23
      hamartomas were diagnosed. Seventeen masses were visible on mammography, and 82%
      were homogeneously dense. Of 36 masses shown on sonography, 86% were uniformly
      hypoechoic. At histologic examination, only 16% contained fat within the mass.
      CONCLUSIONS: Hamartomas may appear as homogeneously dense, well-circumscribed
      masses, varying in appearance from the classically described encapsulated mixed
      fatty-fibroglandular mass. Pathologists can make the diagnosis of hamartoma
      without the presence of adipose tissue but may have difficulty in distinguishing
      the hamartoma from fibrocystic change. However, if there is radiologic-pathologic
      concordance, further surgical excision is not warranted.

PMID- 15448316
TI  - Tuberculosis of the parotid gland: sonographic manifestations and sonographically
      guided aspiration.
AB  - OBJECTIVE: Involvement of the parotid gland by tuberculosis (TB) is rare. If
      treated properly, the prognosis of TB of the parotid gland is good. In this
      retrospective study, we report our experience with sonography and sonographically
      guided aspiration in the diagnosis of parotid TB. METHODS: Over 12 years, 9
      adults (mean age, 48 years) with parotid gland TB had been examined with high
      resolution sonography and color Doppler sonography for their clinical problems of
      swelling on the mandibular angle. Sonographically guided fine-needle aspiration
      was done for cytologic study, stains for acid-fast bacilli, and cultures for
      mycobacterium. RESULTS: The sonographic patterns were classified as chiefly the
      parenchymal type (4 patients) and chiefly the periparotid type (5 patients). The
      parenchymal type appeared as a diffusely enlarged, comparatively hypoechoic gland
      (compared with the contralateral asymptomatic gland), with or without focal
      intraparotid nearly anechoic zones, which might have a cavity or cavities within
      it. The periparotid type appeared as hypoechoic nodules located in the peripheral
      zone of the hyperechoic parotid gland, consistent with enlarged periglandular
      lymph nodes. The diagnosis of parotid TB was made in 8 of 9 patients on the basis
      of sonographically guided aspiration for acid-fast bacilli stains, cytologic
      study, and cultures for mycobacterium. CONCLUSIONS: Sonographic examination
      contributes substantially in the diagnosis of parotid TB infection. In the
      presence of diffuse parotid echo pattern changes with periparotid
      lymphadenopathy, and with or without focal hypoechoic zones, TB infection should
      be differentiated. Sonographically guided fine-needle aspiration may provide
      further diagnostic information by means of stains, cultures, and cytologic study.

PMID- 15448317
TI  - Sonographic features of an intraductal polypoid mass: differentiation between
      hepatocellular carcinoma and intraductal cholangiocarcinoma.
AB  - OBJECTIVE: To identify laboratory and sonographic features capable of
      differentiating hepatocellular carcinoma (HCC) invading the bile duct from
      intraductal cholangiocarcinoma (IDCCC). METHODS: Nine patients with HCC invading
      the bile duct and 8 patients with IDCCC were found in our radiologic and
      pathologic database. Laboratory (alpha-fetoprotein, cancer antigen 19-9, total
      bilirubin, and alkaline phosphatase) and sonographic findings were
      retrospectively reviewed by 2 reviewers by consensus. Sonographic findings
      included the presence and echo texture of parenchymal masses, the margin and echo
      texture of intraductal masses, continuity between parenchymal and intraductal
      masses, cystic ductal dilatation or wall thickening of the bile duct, and the
      presence of associated chronic liver disease. RESULTS: Significant differences
      were found in the levels of total bilirubin (14 versus 3.5 mg/dL), alpha
      fetoprotein (2984 versus 5 ng/mL), and cancer antigen 19-9 (8574 versus 1861
      U/mL) in HCC and IDCCC (P <.05). Echogenicity of the intraductal masses was iso
      or low in 8 (88.9%) of 9 HCCs and 3 (37.5%) of 8 IDCCCs (P <.05). In all 7
      patients with HCC but in no patient with IDCCC, the parenchymal masses were
      contiguous with the intraductal masses (P <.05). Cystic ductal dilatation of bile
      duct was seen in 8 (88.9%) of 9 HCCs and 3 (37.5%) of 8 IDCCCs (P <.05). All 9
      (100%) of 9 HCCs and 3 (37.5%) of 8 IDCCCs were associated with chronic liver
      disease (P <.05). Parenchymal masses occurred in 7 patients with HCC (77.8%) and
      in 3 patients with IDCCC (37.5%), but the difference was not statistically
      significant (P =.153). The margins of the intraductal masses were smooth in all 9
      (100%) of 9 HCCs and lobulated in 3 (37.5%) of 8 IDCCCs (P =.082). CONCLUSIONS:
      Combined interpretation of laboratory and sonographic features may help in the
      differentiation of HCC with bile duct invasion and IDCCC.

PMID- 15448318
TI  - Nature of Doppler perfusion index changes in patients with colorectal cancer
      liver metastases.
AB  - OBJECTIVE: Occult hepatic metastases from colorectal cancer result in an increase
      of the ratio of arterial hepatic blood flow to total hepatic blood flow,
      described as the Doppler perfusion index. Whether this alteration is due to an
      increase in arterial blood flow or a decrease in portal venous inflow has not yet
      been unequivocally determined. The purpose of this study was to analyze changes
      in hepatic perfusion in patients with liver metastases from colorectal cancer by
      standardization of hemodynamic parameters to body surface area. METHODS:
      Hemodynamic parameters (crosssectional area, blood flow, and congestive index)
      were measured for the common hepatic artery and portal vein with duplex color
      Doppler sonography in 20 patients with liver metastases and 20 healthy control
      subjects and evaluated relative to body surface area. RESULTS: No statistically
      significant differences in age, body surface area, cross-sectional area of the
      common hepatic artery, and congestion index of the common hepatic artery and
      portal vein were observed between control subjects and patients with liver
      metastases. Patients with liver metastases had significantly greater arterial
      hepatic blood flow and Doppler perfusion index and significantly smaller portal
      cross-sectional area portal blood flow as well as total liver blood flow (P
      <.001). CONCLUSIONS: This study supports the theory that the primary mechanism of
      alteration in liver perfusion is the reduction of portal inflow with subsequently
      increased arterial hepatic blood flow.

PMID- 15448319
TI  - Sonographic evaluation of the carpal tunnel after provocative exercises.
AB  - OBJECTIVE: Dynamic carpal tunnel syndrome (CTS) is a subtype of CTS in which
      symptoms usually subside with rest and return with repetitive motions. In this
      subgroup, nerve conduction studies, performed at rest, are often inconclusive. In
      this study, the diagnostic value of provocative sonography was evaluated in
      patients with dynamic CTS. METHODS: Twenty wrists of 13 patients with dynamic CTS
      and 10 control subjects were investigated with sonography before and immediately
      after provocative exercises imitating work-related stresses. In addition to
      conventional indices (palmar displacement, nerve area at the middle level, and
      swelling ratio before and after exercise), 2 newly formed indices (provocative
      nerve area ratio and provocative palmar displacement ratio) were investigated.
      RESULTS: In the pre-exercise period, there were no significant differences
      between patients and control subjects regarding palmar displacement and the
      swelling ratio. The difference was significant (P =.035) for the nerve area at
      the middle level. In the post-exercise period, all parameters were significantly
      different between patients and control subjects. The nerve area at the middle
      level and the swelling ratio had higher significance (P <.0001) than palmar
      displacement (P =.015). The post-exercise swelling ratio had the highest
      sensitivity (95%) in diagnosing dynamic CTS when a cutoff value of 1.26 was used.
      The provocative palmar displacement ratio had high sensitivity (80%) and the
      highest specificity (90%) for a cutoff value of 1.28. CONCLUSIONS: Provocative
      exercises increase sensitivity and specificity and contribute to the sonographic
      diagnosis of dynamic CTS. This examination should be performed if
      electrodiagnostic test results are negative.

PMID- 15448320
TI  - Sonographic evaluation of bladder volume in diabetic children and adolescents
      compared with nondiabetic subjects.
AB  - OBJECTIVES: An increase in volume and evidence of postvoiding residuals are both
      encountered in the bladder of diabetic patients and can lead to urinary tract
      infections and impair renal function. Our objective was to compare the bladder
      volume of diabetic children and adolescents with that of nondiabetic subjects.
      METHODS: We investigated 247 diabetic patients and 228 control subjects between
      the ages 3 and 21 years. The sonographic examination was performed with a full
      bladder, after spontaneous voiding, and after forced voiding. Three dimensions
      were determined: longitudinal, transverse, and anteroposterior transverse. The
      data were analyzed by the Chi2 test, analysis of variance, the Kruskal-Wallis
      test, and multivariate regression. RESULTS: The 2 groups were equivalent for age
      (P =.56) and sex (P =.82). The median full bladder volume was larger in the
      diabetic group (268 mL) than in the control group (220 mL; P =.0004). Postvoiding
      residual volume after spontaneous and forced voiding was significantly higher in
      the diabetic group (P <.0001). Multivariate analysis showed that being diabetic
      (P =.021), older than 9 years (P =.000), and female (P =.036) all influenced full
      bladder volume. CONCLUSIONS: Sonographic evaluation showed incipient bladder
      dysfunction in diabetic patients. The multivariate analysis showed that the
      increase in bladder volume had a association with age (>9 years), female sex, and
      mean glycosylated hemoglobin value. Thus, bladder volume evaluation by sonography
      should be incorporated in the routine assessment of patients with type 1
      diabetes.

PMID- 15448321
TI  - Cerebral blood flow velocity before and after cerebrospinal fluid drainage in
      infants with posthemorrhagic hydrocephalus.
AB  - OBJECTIVE: Currently, the timing and volume of cerebrospinal fluid (CSF) drainage
      are determined by subjective clinical findings in infants with posthemorrhagic
      hydrocephalus. The aim of this study was to determine whether measurement of the
      resistive index is useful for management of CSF drainage in these infants.
      METHODS: We measured the resistive index in the anterior cerebral artery (RI-ACA)
      by using pulsed Doppler sonography before and after lumbar or subcutaneous
      ventricular catheter reservoir punctures in 7 infants with posthemorrhagic
      hydrocephalus. RESULTS: The increased RI-ACA values (mean +/- SD, 0.86 +/- 0.04;
      range, 0.80-0.89) decreased significantly (0.76 +/- 0.05; 0.64-0.83) after
      removal of CSF at a rate of 5 to 10 mL/kg (P <.0001). CONCLUSIONS: We suggest
      that measurement of the RI-ACA may be useful for evaluating the efficacy of CSF
      drainage and to determine how much CSF should be removed in hydrocephalic
      infants.

PMID- 15448322
TI  - Analysis of the thymus in 151 healthy infants from 0 to 2 years of age.
AB  - OBJECTIVE: A prospective sonographic study of the normal thymus was performed to
      determine the size changes with age and to compare the results according to some
      clinical conditions, such as sex, breast versus formula feeding, and term or
      preterm status. METHODS: One hundred fifty-one healthy infants underwent thymic
      sonography. Maximal transverse and longitudinal dimensions and anteroposterior
      dimensions of the right and left lobes were measured, and thymic indices were
      calculated. Mean values of thymic measurements for each group (sex, age, breast
      or formula feeding, and term or preterm status) were determined. The results were
      statistically evaluated. RESULTS: Thymic dimensions showed the maximal values at
      about 4 to 6 months and gradually decreased after 6 to 8 months. No significant
      differences were found between mean values of thymic dimensions according to the
      sex and formula- versus breast-fed groups. As expected, the term group had
      greater thymic size values than the preterm group, probably because of positive
      correlations between thymus size, birth weight, and height. CONCLUSIONS: The
      thymus is clearly and easily visualized on sonography in the 0- to 2-year age
      period. This may be useful for evaluating qualitative and quantitative properties
      of the thymus and determining size changes according to age in various clinical
      conditions.

PMID- 15448323
TI  - Fetal nasal bone length in euploid and aneuploid fetuses between 11 and 20 weeks'
      gestation: a prospective study.
AB  - OBJECTIVE: To develop normative data for nasal bone length between 11 and 20
      weeks' gestation and to assess the utility of nasal bone hypoplasia in the
      detection of fetal aneuploidy in the second trimester. METHODS: Well-dated,
      nonanomalous fetuses were examined between 11 and 20.9 weeks' gestation. The
      nasal bone was assessed and measured, and normative data from 11 to 20 weeks'
      gestation were determined. The nasal bone lengths in fetuses with confirmed
      aneuploidy were compared with the normative data. RESULTS: The fetal nasal bone
      length increased linearly with advancing gestational age. Nomograms including the
      10th, 50th, and 90th percentiles were created. Nasal bone hypoplasia was seen in
      6 of 6 cases of fetal trisomy in the second trimester. CONCLUSIONS: Nasal bone
      hypoplasia in the early second trimester identifies a cohort of fetuses at high
      risk for aneuploidy.

PMID- 15448324
TI  - The use of the minimum projection mode in 4-dimensional examination of the fetal
      heart with spatiotemporal image correlation.
AB  - OBJECTIVE: The minimum projection mode (MPM) is a rendering algorithm available
      in some 3- and 4-dimensional ultrasonography systems that, in 1 image, allows the
      visualization of vessels and cystic anatomic structures located in different
      scanning planes. The objective of this study was to compare the information
      displayed in images obtained with the MPM with their corresponding 2-dimensional
      ultrasonographic images from fetuses with and without structural heart defects.
      METHODS: Thirty-two volume data sets acquired with the spatiotemporal image
      correlation technique from fetuses with (n = 15) and without (n = 17) structural
      heart defects were analyzed. Rendered images of the upper abdomen, 4-chamber
      view, and 3-vessel view were compared with the corresponding 2-dimensional
      images. Two independent observers with experience in fetal echocardiography
      reviewed these volume data sets using the MPM. The visualization rate of specific
      anatomic structures seen from a transverse sweep of the heart was recorded for
      each observer, and the interobserver agreement was assessed by statistical
      indices of agreement (kappa statistic). RESULTS: Images obtained by the MPM
      displayed more vascular structures than those of corresponding 2-dimensional
      images at the level of the 3-vessel view. For conotruncal anomalies, the minimum
      mode projected the aorta and pulmonary arteries in 1 single plane, facilitating
      the understanding of their spatial relationships. The interobserver agreement
      score was moderate to "almost perfect" for assessment of most anatomic structures
      in the upper abdomen, 4-chamber view, and 3-vessel view sections. However,
      interobserver agreement ranged from fair to poor for visualization of the left
      outflow tract, atrial septum, and flap of the foramen ovale. CONCLUSIONS: The MPM
      is an alternative rendering modality that facilitates visualization of normal and
      abnormal vascular connections to the fetal heart at the level of the 3-vessel
      view. This technique may be useful in prenatal diagnosis of conotruncal anomalies
      and in assessment of the spatial relationships of abnormal vascular connections
      in the upper mediastinum.

PMID- 15448325
TI  - Drug delivery into the eye with the use of ultrasound.
AB  - OBJECTIVE: To evaluate ultrasound enhancement of drug delivery through the cornea
      and the histologic appearance of the cornea up to 24 hours after treatment.
      METHODS: Corneas were exposed to ultrasound at a frequency of 880 kHz and
      intensities of 0.19 to 0.56 W/cm2 (continuous mode) with an exposure duration of
      5 minutes. The aqueous humor concentration of a topically applied hydrophilic
      dye, sodium fluorescein, was determined quantitatively in ultrasound- and sham
      treated rabbit eyes in vivo. Gross and light microscopic examinations were used
      to observe structural changes in the cornea 0 to 24 hours after ultrasound
      exposure. Cavitation activity was measured with a passive cavitation detector.
      RESULTS: Most cells with an appearance different from that of the normal cells
      were present in the surface layer of the corneal epithelium. No structural
      changes were observed in the stroma. The increase in dye concentration in the
      aqueous humor (relative to sham treatment), after the simultaneous application of
      ultrasound and the dye solution, was 2.4 times at 0.19 W/cm2, 3.8 times at 0.34
      W/cm2, and 10.6 times at 0.56 W/cm2 (P <.05). Dye delivery was found to increase
      with increasing ultrasound intensity, which corresponded to an increase in
      cavitation activity. Corneal pits, observed in the ultrasound-treated epithelium,
      completely disappeared within 90 minutes. CONCLUSIONS: Application of 880-kHz
      ultrasound provided up to 10-fold enhancement in the delivery of a hydrophilic
      compound through the cornea while producing minor changes in the corneal
      epithelium.

PMID- 15448326
TI  - Sonographic mimics of renal calculi.
AB  - OBJECTIVES: To review sonographic findings that can mimic renal calculi. METHODS:
      We comment on a number of echoes that can mimic renal calculi. RESULTS: There are
      a number of sonographic renal artifacts, vascular and nonvascular, that may
      confound a correct diagnosis. CONCLUSIONS: Awareness of these potential artifacts
      will result in a more specific sonographic examination and will accurately guide
      the referring physician toward appropriate patient treatment. The importance of
      other imaging modalities is also emphasized to ensure that a correct diagnosis is
      obtained whenever the sonographic findings are inconclusive.

PMID- 15448327
TI  - Three-dimensional sonography in diagnosis of retroperitoneal hemorrhage from
      adrenocortical carcinoma.

PMID- 15448328
TI  - Whirlpool sign in small-bowel volvulus due to a mesenteric cyst.

PMID- 15448329
TI  - Sharp-angled lumbosacral kyphosis.

PMID- 15448330
TI  - Congenital masses of the lung, cystic adenomatoid malformation versus congenital
      lobar emphysema: prenatal diagnosis and implications for postnatal treatment.

PMID- 15448331
TI  - Myocardial calcification in a fetus: a distinctive presentation of in utero
      herpes simplex virus type II infection.

PMID- 15448332
TI  - Prenatal diagnosis of an inguinoscrotal hernia in a fetus with cystic fibrosis.

PMID- 15448333
TI  - Sonographic diagnosis of gallstone ileus.

PMID- 15448334
TI  - Triple gallbladder: preoperative sonographic diagnosis.

PMID- 15448335
TI  - Glycosyltransferases encoded by viruses.
AB  - Studies of cellular biology in recent decades have highlighted the crucial roles
      of glycans in numerous important biological processes, raising the concept of
      glycomics that is now considered as important as genomics, transcriptomics and
      proteomics. For millions of years, viruses have been co-evolving with their
      hosts. Consequently, during this co-evolution process, viruses have acquired
      mechanisms to mimic, hijack or sabotage host processes that favour their
      replication, including mechanisms to modify the glycome. The importance of the
      glycome in the regulation of host-virus interactions has recently led to a new
      concept called 'glycovirology'. One fascinating aspect of glycovirology is the
      study of how viruses affect the glycome. Viruses reach that goal either by
      regulating expression of host glycosyltransferases or by expressing their own
      glycosyltransferases. This review describes all virally encoded
      glycosyltransferases and discusses their established or putative functions. The
      description of these enzymes illustrates several intriguing aspects of virology
      and provides further support for the importance of glycomics in biological
      processes.

PMID- 15448336
TI  - Epstein-Barr virus nuclear antigen 1 is a DNA-binding protein with strong RNA
      binding activity.
AB  - Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA-1) plays key roles in both the
      regulation of gene expression and the replication of the EBV genome in latently
      infected cells. To characterize the RNA-binding activity of EBNA-1, it was
      demonstrated that EBNA-1 binds efficiently to RNA homopolymers that are composed
      of poly(G) and weakly to those composed of poly(U). All three RGG boxes of EBNA-1
      contributed additively to poly(G)-binding activity and could mediate RNA binding
      when attached to a heterologous protein in an RNA gel mobility-shift assay. In
      vitro-transcribed EBV and non-EBV RNA probes revealed that EBNA-1 bound to most
      RNAs examined and the affinity increased as the content of G and U increased, as
      demonstrated in competition assays. Among these probes, the 5' non-coding region
      (NCR) (nt 131-278) of hepatitis C virus RNA appeared to be the strongest
      competitor for EBNA-1 binding to the EBV-encoded small nuclear RNA 1 (EBER1)
      probe, whereas a mutant 5' NCR RNA with partially disrupted secondary structure
      was a weak competitor. Furthermore, the interaction of endogenous EBNA-1 and
      EBER1 in EBV-infected cells was demonstrated by a ribonucleoprotein
      immunoprecipitation assay. These results revealed that EBNA-1 is a DNA-binding
      protein with strong binding activity to a relatively broad spectrum of RNA and
      suggested an additional biological impact of EBNA-1 through its ability to bind
      to RNA.

PMID- 15448337
TI  - Capacity of Epstein-Barr virus to infect monocytes and inhibit their development
      into dendritic cells is affected by the cell type supporting virus replication.
AB  - Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus that is involved in
      the pathogenesis of a wide spectrum of malignant and non-malignant diseases.
      Strong evidence implicates T lymphocytes in the control of EBV replication and
      tumorigenesis, but cellular components of the innate immune system are poorly
      characterized in terms of their function in the development of EBV-specific
      immunity or interaction with the virus. This study demonstrates that EBV virions
      produced in epithelial cells surpass their B cell-derived counterparts in the
      capacity to enter monocytes and inhibit their development into dendritic cells
      (DCs). Different ratios of the gp42 and gH glycoproteins in the envelope of
      virions that were derived from major histocompatibility complex class II-positive
      or -negative cells accounted primarily for the differences in EBV tropism. EBV is
      shown to enter both monocytes and DCs, although the cells are susceptible to
      virus-induced apoptosis only if infected at early stages of DC differentiation.
      The purified gH/gL heterodimer binds efficiently to monocytes and DCs, but not to
      B cells, suggesting that high expression levels of a putative binding partner for
      gH contribute to virus entry. This entry takes place despite very low or
      undetectable expression of CD21, the canonical EBV receptor. These results
      indicate that the site of virus replication, either in B cells or epithelial
      cells, alters EBV tropism for monocytes and DCs. This results in a change in the
      virus's immunomodulating capacity and may have important implications for the
      regulation of virus-host interactions during primary and chronic EBV infection.

PMID- 15448338
TI  - Inhibition of infectious human herpesvirus 8 production by gamma interferon and
      alpha interferon in BCBL-1 cells.
AB  - Human herpesvirus-8 (HHV-8) is aetiologically linked to Kaposi's sarcoma and
      primary effusion lymphoma. Although interferon-alpha (IFN-alpha) and interferon
      gamma (IFN-gamma) are both antiviral cytokines, IFN-alpha blocks entry of HHV-8
      into the lytic phase, whereas IFN-gamma induces an increase in the percentage of
      cells undergoing lytic replication. Multiple events in the lytic cascade must be
      completed to produce infectious virus. The ability of both types of IFN to affect
      the production of infectious virus was explored. Both IFN-alpha and IFN-gamma
      induced expression of the antiviral proteins double-stranded RNA-activated
      protein kinase (PKR) and 2'5'-oligoadenylate synthetase (2'5'-OAS) in HHV-8
      infected BCBL-1 cells. Higher levels resulted from incubation with IFN-alpha than
      with IFN-gamma, whereas IFN-gamma induced higher levels of IRF-1 than did IFN
      alpha. IFN-gamma induced a minor increase in lytic viral gene expression, which
      was not accompanied by a detectable increase in infectious virus. When lytic
      replication of HHV-8 was induced using TPA, high levels of infectious virus
      appeared in the conditioned medium. When IFN-gamma was present during TPA
      stimulation, the production of infectious virus was reduced by at least a 60 %,
      and IFN-alpha fully blocked TPA-induced production of infectious virus. The
      greater reduction of viral production that occurred with IFN-alpha is consistent
      with the higher levels of the antiviral proteins PKR and 2'5'-OAS induced by IFN
      alpha than by IFN-gamma. These studies indicate that the augmentation of cellular
      antiviral defences by IFN-gamma was sufficient to prevent production of
      infectious virus despite IFN-gamma-induced entry of some cells into the lytic
      phase of HHV-8 replication.

PMID- 15448339
TI  - The M2 gene product of murine gammaherpesvirus 68 is required for efficient
      colonization of splenic follicles but is not necessary for expansion of latently
      infected germinal centre B cells.
AB  - Infection of mice with murine gammaherpesvirus 68 is characterized by a marked
      transient expansion of latently infected splenic germinal centre (GC) B cells,
      which is followed by lower levels of persistent infection in GC and memory B
      cells. Virus transcription within GC B cells is restricted to a number of latency
      associated open reading frames, including M2. This gene encodes a structurally
      unique protein of unknown function, which has been shown to be essential for the
      transient peak of virus latency during the establishment of latent infection in
      the spleen. This study shows that upon infection of mice with M2-defective
      viruses, at 14 days post-infection during the establishment of latency in the
      spleen, there was a reduction in the number of latently infected follicles when
      compared with wild-type virus. However, the mean number of latently infected
      cells within each follicle was equivalent between wild-type and M2-defective
      viruses. Late in infection, disruption of M2 resulted in sustained and abnormally
      high levels of virus persistence in splenic GC B cells but not memory B cells.
      These data indicate that during the establishment of latency in the spleen, the
      M2 gene product is required for efficient colonization of splenic follicles but
      is dispensable for the expansion of latently infected GC B cells and that M2
      might be a critical modulator of B-cell function.

PMID- 15448340
TI  - Analysis of the first complete genome sequence of an Old World monkey adenovirus
      reveals a lineage distinct from the six human adenovirus species.
AB  - Simian adenovirus 3 (SAdV-3) is one of several adenoviruses that were isolated
      decades ago from Old World monkeys. Determination of the complete DNA sequence of
      SAdV-3 permitted the first full genomic comparison of a monkey adenovirus with
      adenoviruses of humans (HAdVs) and chimpanzees, which are recognized formally as
      constituting six of the species (HAdV-A to HAdV-F) within the genus
      Mastadenovirus. The SAdV-3 genome is 34 246 bp in size and has a G+C content of
      55.3 mol%. It contains all the genes that are characteristic of the genus
      Mastadenovirus and has a single VA-RNA gene and six genes in each of the E3 and
      E4 regions. The genetic organization is the same as that of HAdV-12, a member of
      the HAdV-A species. Phylogenetic analyses showed that although SAdV-3 is related
      marginally more closely to HAdV-A and HAdV-F than to other species, it represents
      a unique lineage that branched at an early stage of primate adenovirus
      divergence. The results imply that the genetic layout in SAdV-3 and HAdV-12 may
      also have characterized the common ancestor of all sequenced primate
      adenoviruses.

PMID- 15448341
TI  - Downregulation of major histocompatibility complex class I in bovine papillomas.
AB  - Bovine papillomavirus (BPV) induces papillomas in cattle; in the great majority
      of cases, these regress due to the host immune response, but they can persist and
      progress to malignancy. Even in the absence of malignant transformation, BPV
      infection persists for a significant period of time before activation of the host
      immune system, suggesting that the host immune system is unaware of, or disabled
      by, BPV. E5 is the major oncoprotein of BPV, which, in addition to its
      transforming properties, downregulates the expression and transport to the cell
      surface of major histocompatibility complex class I (MHC I). Here, it is shown
      that co-expression of MHC I and E5 in papillomas caused by BPV-4 infection is
      mutually exclusive, in agreement with the inhibition of surface MHC I expression
      by E5 that is observed in vitro. The inhibition of MHC expression in E5
      expressing papilloma cells could explain the long period that is required for
      activation of the immune response and has implications for the progression of
      papillomas to the malignant stage; absence of peptide presentation by MHC I to
      cytotoxic T lymphocytes would allow the infected cells to evade the host cellular
      immune response and allow the lesions to persist.

PMID- 15448342
TI  - Degradation of hDlg and MAGIs by human papillomavirus E6 is E6-AP-independent.
AB  - An important characteristic of the E6 proteins derived from cancer-associated
      human papillomaviruses (HPVs) is their ability to target cellular proteins for
      ubiquitin-mediated degradation. Degradation of the p53 tumour suppressor protein
      by E6 is known to involve the cellular ubiquitin ligase, E6-AP; however, it is
      presently not known how E6 targets the Drosophila discs large (Dlg) tumour
      suppressor and the membrane-associated guanylate kinase inverted (MAGI) family of
      proteins for degradation. By using an in vitro E6-AP immunodepletion assay, these
      targets were tested for degradation in a E6-AP-dependent manner. The data showed
      clearly that E6 can direct the degradation of Dlg and the MAGI family of proteins
      in the absence of E6-AP in this in vitro system. These results provide compelling
      evidence for the role of E6-associated ubiquitin ligases other than E6-AP in the
      degradation of certain E6 targets.

PMID- 15448343
TI  - Subtypes of BK virus prevalent in Japan and variation in their transcriptional
      control region.
AB  - BK polyomavirus (BKV) is ubiquitous in the human population, infecting children
      without obvious symptoms, and persisting in the kidney in a latent state. In
      immunosuppressed patients, BKV is reactivated and excreted in urine. BKV isolates
      have been classified into four subtypes (I-IV) using either serological or
      genotyping methods. To elucidate the subtypes of BKV prevalent in Japan, the 287
      bp typing region in the viral genome was PCR-amplified from urine samples of 45
      renal transplant (RT) and 31 bone-marrow transplant (BMT) recipients. The
      amplified fragments were subjected to a phylogenetic or RFLP analysis to
      determine the subtypes of BKV isolates in urine samples. Subtypes I, II, III and
      IV were detected, respectively, in 70-80, 0, 2-3 and 10-20 % of the BKV-positive
      patients in both patient groups. This pattern of distribution was virtually
      identical to patterns previously demonstrated in England, Tanzania and the United
      States, suggesting that BKV subtypes are distributed similarly in various human
      populations. Furthermore, transcriptional control regions (TCRs) were PCR
      amplified from the urine samples of 25 RT and 20 BMT recipients, and their
      nucleotide sequences were determined. The basic TCR structure (the so-called
      archetype configuration) was observed in most isolates belonging to subtypes I,
      III and IV (subtype II isolates were not available), albeit with several
      nucleotide substitutions and a few single-nucleotide deletions (or insertions).
      Only three TCRs carried extensive sequence rearrangements. Thus, it was concluded
      that the archetypal configuration of the BKV TCR has been conserved during the
      evolution of BKV.

PMID- 15448344
TI  - Phenotype and function of monocyte derived dendritic cells in chronic hepatitis B
      virus infection.
AB  - The antiviral T cell failure of patients with chronic hepatitis B virus (HBV)
      infection was suggested to be caused by a T cell stimulation defect of dendritic
      cells (DC). To address this hypothesis, monocyte derived DC (MDDC) of patients
      with chronic or resolved acute HBV infection and healthy controls were studied
      phenotypically by FACS analyses and functionally by mixed lymphocyte reaction,
      ELISA, ELISpot and proliferation assays of MDDC cultures or co-cultures with an
      allogeneic HBc-specific Th cell clone. HBV infection of MDDC was studied by
      quantitative PCR. MDDC from HBV patients seemed to be infected by the HBV, showed
      a reduced surface expression of HLA DR and CD40 and exhibited a reduced secretion
      of IL12p70 in response to HBcAg but not to LPS, as compared to control MDDC.
      However, after cytokine induced maturation, MDDC from HBV patients revealed an
      unimpaired phenotype. Moreover, the T cell stimulatory capacity of HBV-DC was
      intact, since (i) the induction of allospecific proliferative and IFN-gamma
      responses was not affected in HBV-MDDC, and (ii) HLA DR7 restricted stimulation
      of an allogeneic HBc-specific Th cell clone was not impaired by HBV-MDDC compared
      to control MDDC. It is hypothesized that HBV infection of DC might lead to minor
      phenotypic and functional alterations without significantly affecting their
      antiviral Th cell stimulatory capacity.

PMID- 15448345
TI  - Apoptosis in lymphoid organs of pigs naturally infected by porcine circovirus
      type 2.
AB  - The objective of the present study was to evaluate the involvement of apoptosis
      in the development of post-weaning multisystemic wasting syndrome (PMWS) lymphoid
      depletion lesions. Twenty-one pigs that were categorized into three different
      lesional severity stages (S1, n=5; S2, n=7; S3, n=9) and five healthy control
      pigs (stage S0) were used. From all pigs, samples of thymus, spleen, tonsil,
      ileum and superficial inguinal lymph node were processed for histological
      examination, in situ hybridization for porcine circovirus type 2 (PCV2) detection
      and cleaved caspase-3 (CCasp3) immunohistochemistry for detection of apoptotic
      cells. PCV2 was quantified in serum samples by using TaqMan real-time PCR. CCasp3
      labelling was measured in the different morphological compartments of all
      lymphoid tissues, using an automated system for quantification. Differences
      between each tissue compartment and lesional stage were assessed, as well as the
      correlation between apoptosis, lesional stage and viral load. Overall, the
      results indicated that the more intense the lymphoid depletion, the lower the
      rate of apoptosis. In the thymus, the cortex was the area where differences
      between PMWS-affected and control animals were more evident; it was found that
      all PMWS-affected pigs had significantly lower rates of apoptosis than the
      controls. In the secondary lymphoid organs, B-cell areas presented higher rates
      of apoptosis; similar apoptotic rates were found in this compartment in control
      and S1 pigs. In S2 and S3, B-cell areas were lost and the apoptotic pattern
      observed was a diffusely distributed low rate of positive cells. Significantly
      lower rates of apoptosis between PMWS-affected pigs and the control group were
      already evident in S1 for the thymus, spleen, superficial inguinal lymph node and
      Peyer's patches, but not for the tonsils. Apoptotic rates in lymphoid tissues
      were correlated inversely with viral load in serum and with severity of lesions.
      In conclusion, the results indicate that apoptosis is not a remarkable feature in
      PMWS lymphoid lesion development.

PMID- 15448346
TI  - Virus entry or the primary infection cycle are not the principal determinants of
      host specificity of Spodoptera spp. nucleopolyhedroviruses.
AB  - The multicapsid nucleopolyhedroviruses (NPVs) of Spodoptera exigua (SeMNPV),
      Spodoptera frugiperda (SfMNPV), and Spodoptera littoralis (SpliNPV) are
      genetically similar (78 % similarity) but differ in their degree of host
      specificity. Infection by each of the three NPVs in these three Spodoptera host
      species was determined by oral inoculation of larvae with occlusion bodies (OBs)
      or intrahaemocoelic injection with occlusion derived virions (ODVs). RT-PCR
      analysis of total RNA from inoculated insects, targeted at immediate early (ie
      0), early (egt, DNA polymerase), late (chitinase) and very late genes
      (polyhedrin), indicated that each of the NPVs initiated an infection in all three
      host species tested. SpliMNPV produced a fatal NPV disease in both heterologous
      hosts, S. frugiperda and S. exigua, by oral inoculation or injection. SfMNPV was
      lethal to heterologous hosts, S. exigua and S. littoralis, but infected larvae
      did not melt and disintegrate, and progeny OBs were not observed. SeMNPV was able
      to replicate in heterologous hosts and all genes required for replication were
      present in the genome, as the virus primary infection cycle was observed.
      However, gene expression was significantly lower in heterologous hosts. SeMNPV
      pathogenesis in S. frugiperda and S. littoralis was blocked at the haemocoel
      transmission stage and very nearly cleared. SeMNPV mixtures with SpliMNPV or
      SfMNPV did not extend the host range of SeMNPV; in all cases, only the homologous
      virus was observed to proliferate. It is concluded that entry and the primary
      virus infection cycle are not the only, or the major determinants, for SeMNPV
      infection of heterologous Spodoptera species.

PMID- 15448347
TI  - Association of Sf9 cell proliferating cell nuclear antigen with the DNA
      replication site of Autographa californica multicapsid nucleopolyhedrovirus.
AB  - The accumulation of cellular proliferating cell nuclear antigen (PCNA) in the
      nucleus of Sf9 cells has been shown to increase upon infection with Autographa
      californica multicapsid nucleopolyhedrovirus (AcMNPV). Here, analysis by DNase I
      treatment and chromatin immunoprecipitation revealed that cellular PCNA in the
      nucleus of Sf9 cells bound AcMNPV DNA. Immunocytochemical analysis showed
      colocalization of Sf9 cell PCNA and AcMNPV DNA replication sites. Similar
      colocalization was also observed in BmN-4 cells infected with Bombyx mori NPV,
      which is inherently missing the pcna gene. The amount of cellular PCNA associated
      with viral DNA replication sites was greater in cells infected with pcna
      defective AcMNPV mutants than in cells infected with wild-type AcMNPV. These
      results suggest that both cellular and viral PCNAs are involved in AcMNPV DNA
      replication and that pcna-defective AcMNPV mutants are able to substitute
      cellular PCNA for viral PCNA.

PMID- 15448348
TI  - Anticarsia gemmatalis multicapsid nucleopolyhedrovirus v-trex gene encodes a
      functional 3' to 5' exonuclease.
AB  - The viral three-prime repair exonuclease (v-trex) gene of the Anticarsia
      gemmatalis multicapsid nucleopolyhedrovirus (AgMNPV) is the first baculovirus
      gene to be described with significant homology to a 3' exonuclease. v-trex is an
      early gene that is expressed by AgMNPV from 3 h post-infection. In the present
      study, the AgMNPV v-trex ORF was cloned into the baculovirus Autographa
      californica multicapsid nucleopolyhedrovirus (AcMNPV) under the control of a
      polyhedrin promoter. The resulting virus produced an abundant, soluble protein
      that migrated with an apparent size of 23.7 kDa. The 3' to 5' exonuclease
      activity associated with this v-trex-expressing recombinant AcMNPV was 2000-fold
      above that of wild-type AcMNPV. This exonuclease activity was inhibited by EDTA
      and was activated in the presence of Mg2+ and, to a lesser extent, Mn2+. From
      these results, the AgMNPV v-trex gene is concluded to encode an independently
      active 3' to 5' exonuclease.

PMID- 15448349
TI  - Isolation and characterization of a Cotesia rubecula bracovirus gene expressed in
      the lepidopteran Pieris rapae.
AB  - Polydnaviruses are endogenous particles that are crucial for the survival of
      endoparasitoid wasps, providing active suppression of the immune function of the
      lepidopteran host in which wasp larvae develop. The Cotesia rubecula bracovirus
      (CrBV) is unique in that only four gene products are detected in larval host
      (Pieris rapae) tissues and expression of CrBV genes is transient, occurring
      between 4 and 12 h post-parasitization. Two of the four genes, CrV1 and CrV3,
      have been characterized. CrV1 is a secreted glycoprotein that has been implicated
      in depolymerization of the actin cytoskeleton of host haemocytes, leading to
      haemocyte inactivation; CrV3 is a multimeric C-type lectin that shares homology
      with insect immune lectins. Here, a third CrBV-specific gene is described, CrV2,
      which is expressed in larval P. rapae tissues. CrV2, which is transcribed in
      haemocytes and fat body cells, has an ORF of 963 bp that produces a glycoprotein
      of approximately 40 kDa. CrV2 is secreted into haemolymph and appears to be
      internalized by host haemocytes. CrV2 has a coiled-coil region predicted at its C
      terminus, which may be involved in the formation of putative CrV2 trimers that
      are detected in haemolymph of parasitized host larvae.

PMID- 15448350
TI  - Identification and characterization of a novel gene of grouper iridovirus
      encoding a purine nucleoside phosphorylase.
AB  - Purine nucleoside phosphorylase (PNP) is a key enzyme in the purine salvage
      pathway. It catalyses the reversible phosphorolysis of purine (2'
      deoxy)ribonucleosides to free bases and (2'-deoxy)ribose 1-phosphates. Here, a
      novel piscine viral PNP gene that was identified from grouper iridovirus (GIV), a
      causative agent of an epizootic fish disease, is reported. This putative GIV PNP
      gene encodes a protein of 285 aa with a predicted molecular mass of 30 332 Da and
      shows high similarity to the human PNP gene. Northern and Western blot analyses
      of GIV-infected grouper kidney (GK) cells revealed that PNP expression increased
      in cells with time from 6 h post-infection. Immunocytochemistry localized GIV PNP
      in the cytoplasm of GIV-infected host cells. PNP-EGFP fusion protein was also
      observed in the cytoplasm of PNP-EGFP reporter construct-transfected GK and HeLa
      cells. From HPLC analysis, the recombinant GIV PNP protein was shown to catalyse
      the reversible phosphorolysis of purine nucleosides and could accept guanosine,
      inosine and adenosine as substrates. In conclusion, this is the first report of a
      viral PNP with enzymic activity.

PMID- 15448351
TI  - Important B-cell epitopes for neutralization of human immunodeficiency virus type
      1 Tat in serum samples of humans and different animal species immunized with Tat
      protein or peptides.
AB  - The Tat regulatory protein of human immunodeficiency virus type 1 (HIV-1) is
      secreted by infected cells and plays a key role in viral pathogenesis and
      replication. Tat protein has been proposed as a target antigen for vaccine design
      since anti-Tat antibodies may interfere with virus spread and disease
      progression. The aim of this study was to analyse the serum antibody response of
      mice, rabbits, macaques and humans immunized with recombinant Tat, synthetic Tat,
      Tat toxoid or Tat peptides and to examine the biological properties of these
      antibodies in terms of Tat-induced transactivation and HIV-1 replication. Only
      sera with antibody specificity to both N-terminal and basic functional domains
      were able to inhibit extracellular Tat-dependent transactivation significantly in
      vitro. Antibodies from a human subject immunized with Tat also reduced HIV-1
      replication in acutely infected T cells and blocked reactivation of virus
      replicating low levels in chronically infected cells by exogenous Tat. These
      results demonstrate that immunization with Tat protein or a combination of
      synthetic Tat peptides elicits the production of Tat-neutralizing serum
      antibodies and suggest that Tat vaccination could be used to block in vivo
      extracellular Tat autocrine/paracrine transactivation of HIV-1 replication.

PMID- 15448352
TI  - Selected amino acid substitutions in the C-terminal region of human
      immunodeficiency virus type 1 capsid protein affect virus assembly and release.
AB  - The capsid protein (CA or p24) of human immunodeficiency virus type 1 (HIV-1)
      plays a major role both early and late in the virus replication cycle. Many
      studies have suggested that the C-terminal domain of this protein is involved in
      dimerization and proper assembly of the viral core. Point mutations were
      introduced in two conserved sites of this region and their effects on viral
      protein expression, particle assembly and infectivity were studied. Eight
      different mutants (L205A+P207A, L205A, P207A, 223GPG225AAA, G223A, P224A, G225A
      and V221G) of the infectious clone pNL4-3 were constructed. Most substitutions
      had no substantial effect on HIV-1 protein synthesis, yet they impaired viral
      infectivity and particle production. The two mutants P207A and V221G also had a
      profound effect on Gag-Pol protein processing in HeLa-tat cells. However, these
      results were cell line-specific and Gag-Pol processing of P207A was not affected
      in 293T cells. In HeLa-tat cells, no virus particles were detected with the P207A
      mutation, whereas the other mutant virus particles were heterogeneous in size and
      morphology. None of the mutants showed normal, mature, conical core structures in
      HeLa-tat cells. These results indicate that the two conserved sequences in the C
      terminal CA domain are essential for proper morphogenesis and infectivity of HIV
      1 particles.

PMID- 15448353
TI  - Vaccine protection from CD4+ T-cell loss caused by simian immunodeficiency virus
      (SIV) mac251 is afforded by sequential immunization with three unrelated vaccine
      vectors encoding multiple SIV antigens.
AB  - Candidate human immunodeficiency virus (HIV) vaccine strategies that induce
      strong cellular immune responses protect rhesus macaques that are infected with
      recombinant simian/human immunodeficiency virus SHIV89.6p from acute CD4+ T-cell
      loss and delay progression to AIDS. However, similar strategies have not proven
      as efficacious in the simian immunodeficiency virus (SIV)mac model of AIDS, an
      infection that causes a slow, steady loss of CD4+ T-cell function and numbers in
      rhesus macaques similar to that caused by HIV-1, the principal cause of AIDS in
      humans. Efforts to increase vaccine efficacy by repeated boosting with the same
      vector are quickly limited by rising anti-vector immune responses. Here, the
      sequential use of three different vectors (DNA, Semliki Forest virus and modified
      vaccinia virus Ankara) encoding the same SIVmac structural and regulatory
      antigens was investigated and demonstrated to prevent or slow the loss of CD4+ T
      cells after mucosal challenge with the highly pathogenic SIVmac251 strain. Of
      particular interest was an inverse association between the extent of T-helper 2
      cytokine responses and steady-state virus load. Although limited in the number of
      animals, this study provides important proof of the efficacy of the triple-vector
      vaccine strategy against chronic, progressive CD4+ T-cell loss in the rigorous
      SIVmac/rhesus macaque model of AIDS.

PMID- 15448354
TI  - Cell-cycle dependence of foamy virus vectors.
AB  - Retroviruses differ in the extent to which they are dependent on host-cell
      proliferation for their replication, an aspect of their replication that impacts
      on their vector potential. Foamy viruses offer distinct advantages over other
      retroviruses for development as vectors for gene therapy. A vector derived from
      the prototypic foamy virus (PFV), formerly known as human foamy virus (HFV),
      transduced aphidicolin-arrested cells five- to tenfold more efficiently than one
      derived from murine leukemia virus (MLV), but several-fold less efficiently than
      a human immunodeficiency virus type 1 (HIV-1) vector. The same relative
      efficiency was found following transduction of cells that had been arrested by
      gamma-irradiation or with mitomycin C. Cells that were exposed to vector during
      aphidicolin arrest and were subsequently allowed to cycle were transduced
      significantly better by PFV than by MLV. Quiescent human CD34+ progenitor cells
      were transduced as efficiently by PFV as by HIV vectors (40-50 %) when
      transduction was assayed after the cells were allowed to cycle.

PMID- 15448355
TI  - Feline foamy virus Tas protein is a DNA-binding transactivator.
AB  - Foamy viruses (FVs) harbour a transcriptional transactivator (Tas) and two Tas
      responsive promoter regions, one in the 5' long terminal repeat (LTR) and the
      other an internal promoter (IP) in the envelope gene. To analyse the mechanism of
      transactivation of the FVs, the specificity of feline FV (FFV) Tas protein, which
      is more distantly related to the respective proteins of non-human primate origin,
      were investigated. FFV Tas has been shown specifically to activate gene
      expression from the cognate promoters. No cross-transactivation was noted of the
      prototype foamy virus and human immunodeficiency virus type 1 LTR. The putative
      transactivation response element of FFV Tas was mapped to the 5' LTR U3 region
      (approximately nt -228 to -195). FFV Tas binds to this element in addition to a
      previously described sequence (position -66 to -51). It is therefore concluded
      that FFV Tas is a DNA-binding transactivator that interacts with at least two
      regions in the virus LTR.

PMID- 15448356
TI  - Feline leukaemia virus LTR variation and disease association in a geographical
      and temporal cluster.
AB  - Feline leukaemia virus (FeLV)-945 was previously identified in natural
      multicentric lymphomas and contains a 21 bp tandem triplication in the LTR. In
      the present study, FeLV LTR variation was examined in the cohort from which FeLV
      945 was identified. The objectives of the study were to evaluate FeLV LTR
      variation within the cohort, to determine whether the FeLV-945 LTR was associated
      uniquely with multicentric lymphoma and to evaluate functional attributes that
      may have contributed selective advantage to the predominant LTR variants
      observed. T-cell tumours uniformly contained LTRs with duplicated enhancer
      sequences, although enhancer duplications conferred little transcriptional
      advantage. Non-T-cell malignant, proliferative and degenerative diseases
      contained LTRs with two, three or four tandemly repeated copies of the 21 bp
      sequence originally identified in FeLV-945. While the length and termini of
      enhancer duplications were variable, the 21 bp repeat unit was invariant.
      Triplication of the 21 bp repeat conferred the optimal replicative advantage in
      feline cells.

PMID- 15448357
TI  - Characterization of the complete genomic sequence of genotype II hepatitis A
      virus (CF53/Berne isolate).
AB  - The complete genomic sequence of hepatitis A virus (HAV) CF53/Berne strain was
      determined. Pairwise comparison with other complete HAV genomic sequences
      demonstrated that the CF53/Berne isolate is most closely related to the single
      genotype VII strain, SLF88. This close relationship was confirmed by phylogenetic
      analyses of different genomic regions, and was most pronounced within the capsid
      region. These data indicated that CF53/Berne and SLF88 isolates are related more
      closely to each other than are subtypes IA and IB. A histogram of the genetic
      differences between HAV strains revealed four separate peaks. The distance values
      for CF53/Berne and SLF88 isolates fell within the peak that contained strains of
      the same subtype, showing that they should be subtypes within a single genotype.
      The complete genomic data indicated that genotypes II and VII should be
      considered a single genotype, based upon the complete VP1 sequence, and it is
      proposed that the CF53/Berne isolate be classified as genotype IIA and strain
      SLF88 as genotype IIB. The CF53/Berne isolate is cell-adapted, and therefore its
      sequence was compared to that of two other strains adapted to cell culture, HM
      175/7 grown in MK-5 and GBM grown in FRhK-4 cells. Mutations found at nucleotides
      3889, 4087 and 4222 that were associated with HAV attenuation and cell adaptation
      in HM175/7 and GMB strains were not present in the CF53/Berne strain. Deletions
      found in the 5'UTR and P3A regions of the CF53/Berne isolate that are common to
      cell-adapted HAV isolates were identified, however.

PMID- 15448358
TI  - Sequential modification of translation initiation factor eIF4GI by two different
      foot-and-mouth disease virus proteases within infected baby hamster kidney cells:
      identification of the 3Cpro cleavage site.
AB  - Infection of cells by foot-and-mouth disease virus (FMDV) causes the rapid
      inhibition of cellular cap-dependent protein synthesis that results from cleavage
      of the translation initiation factor eIF4G, a component of the cap-binding
      complex eIF4F. Two FMDV proteins, the leader (L) and 3C proteases, have been
      shown individually to induce cleavage of eIF4GI at distinct sites within baby
      hamster kidney (BHK) cells. Here, sequential cleavage of eIF4GI by the L and 3C
      proteases was demonstrated in FMDV-infected BHK cells. The FMDV 3C cleavage site
      within hamster eIF4GI was localized to a small region (about 40 aa) of the
      protein, between the sites cleaved by the poliovirus 2A protease and the human
      immunodeficiency virus type 2 protease. Human eIF4GI was found to be resistant to
      the action of the FMDV 3C protease. On the basis of amino acid sequence
      alignments, it was predicted and then verified that substitution of a single
      amino acid residue within this region of human eIF4GI conferred sensitivity to
      cleavage by the FMDV 3C protease within cells. Full-length eIF4GI and both forms
      of the C-terminal cleavage product must be capable of supporting the activity of
      the FMDV internal ribosome entry site in directing translation initiation.

PMID- 15448359
TI  - Genetic and phenotypic variations of isolates of shrimp Taura syndrome virus
      found in Penaeus monodon and Metapenaeus ensis in Taiwan.
AB  - Distinct Taura syndrome virus (TSV) isolates were found in Metapenaeus ensis
      (isolate Tw2KMeTSV), Penaeus monodon (isolate Tw2KPmTSV) and Litopenaeus vannamei
      (isolate Tw02LvTSV). Nucleotide sequence analysis of these three isolates
      revealed differences in the TSV structural protein (capsid protein precursor)
      gene orf2. TSV ORF2 amino acid sequence comparison and phylogenetic analysis
      suggested a comparatively close relationship between these three Taiwanese
      isolates and the Hawaiian isolate HI94TSV. In P. monodon specimens that were
      naturally and experimentally infected with the Tw2KPmTSV isolate, the virus was
      contained and shrimps showed no clinical signs of infection. However, when P.
      monodon was challenged with the Tw2KMeTSV isolate, the virus replicated freely.
      The ORF2 amino acid sequence of the Tw2KMeTSV isolate differed from that of
      isolate Tw2KPmTSV in four positions and these differences may account for their
      phenotypic differences, at least in terms of their ability to replicate in
      specific hosts.

PMID- 15448360
TI  - Rhinovirus 3C protease precursors 3CD and 3CD' localize to the nuclei of infected
      cells.
AB  - Human rhinovirus (HRV) 3C protease (3Cpro) plays several important roles in the
      virus replication cycle. This enzyme cleaves the viral polyprotein at discrete
      sites to produce mature viral proteins and also inhibits cellular RNA
      transcription. It is not clear, however, whether the observed transcriptional
      shutoff activities are due to 3Cpro itself or to 3Cpro-containing precursors, and
      where 3Cpro exerts its effects within infected cells. To address these questions
      HeLa cells were infected with HRV-16, stained with polyclonal antibodies directed
      against 3Cpro and then analysed by laser confocal microscopy. Proteins containing
      3Cpro accumulated in nuclei 2-4 h post-infection, and progressively increased in
      the cytoplasm. Analyses of subcellular extracts demonstrated that 3CD', a minor
      component among 3Cpro precursors, gave rise to the earliest 3Cpro nuclear
      signals. Mature 3Cpro and another 3Cpro precursor, 3CD, were also detected in the
      nucleus, cytoplasm and perinuclear membrane fractions 4 h post-infection.
      Transfecting cells with 3Cpro, 3CD precursor and 3CD(Delta371) (with deletion of
      371 aa at the carboxyl terminus of 3D) demonstrated that the nucleolar
      localization signal was near the amino terminus of 3D. In addition, 3Cpro
      precursors were found to co-localize in nuclei with the transcription factor OCT
      1 and the nucleolar chaperone B23. Finally, it was demonstrated that HRV-16
      3Cpro, 3CD and 3CD(Delta371) could cleave OCT-1. Collectively, these findings
      suggest that HRV 3CD' and/or 3CD are specifically localized to the nucleoli of
      infected cells during the early stage of infection, and contribute to the
      inhibition of cellular RNA transcription via a proteolytic mechanism.

PMID- 15448361
TI  - Differential localization of neurons susceptible to enterovirus 71 and poliovirus
      type 1 in the central nervous system of cynomolgus monkeys after intravenous
      inoculation.
AB  - Poliovirus and enterovirus 71 (EV71) are both neurotropic enteroviruses that
      cause serious neurological diseases, such as poliomyelitis and encephalitis. The
      neurovirulence of EV71 in cynomolgus monkeys was demonstrated previously by
      intraspinal inoculation. In this study, an improved simian model of EV71
      infection was established by using intravenous inoculation, which revealed
      clinical and neuropathological similarities between this model and human cases of
      encephalitis. Experimental EV71 infection induced direct neurological
      manifestations, such as tremor, ataxia and brain oedema, but not non-neurological
      complications, such as pulmonary oedema and cardiac failure. Using this model of
      EV71 infection, the neurotropic characteristics of the prototype strains of EV71
      and poliovirus type 1 (PV1) were compared. Three monkeys were inoculated
      intravenously with 10(5.5) TCID50 EV71 and all developed neurological disease
      signs within 4-6 days of inoculation. However, after inoculation with 10(5.5)
      TCID50 PV1 strain OM1 (PV1-OM1), the major manifestation was flaccid paralysis,
      starting from the lower limbs 6-9 days post-inoculation. Histopathological and
      virological analyses of moribund monkeys revealed that disseminated EV71
      infection was characterized by severe panencephalitis involving both the
      pyramidal and extrapyramidal systems. In contrast, the lesions induced by PV1-OM1
      were mainly restricted to the pyramidal tract, particularly the spinal motor
      neurons, thalamus and motor cortex. In conclusion, neuropathological involvement
      in this model correlated well with the apparent differences in neurological
      disease induced by EV71 and PV1-OM1. Thus, intravenous inoculation with EV71 is
      an excellent model to study the neuropathology of EV71 and to evaluate candidate
      vaccines and potential antiviral agents.

PMID- 15448362
TI  - Dissection of measles virus V protein in relation to its ability to block
      alpha/beta interferon signal transduction.
AB  - Interferon (IFN)-alpha and -beta are the main cytokines for innate immune
      responses against viral infections. To replicate efficiently in the hosts,
      viruses have evolved various countermeasures to the IFN response. The V protein
      of measles virus (MV) has been shown to block IFN-alpha/beta signalling. Here,
      the wild-type IC-B strain of MV was shown to grow comparably in the presence and
      absence of IFN-alpha, whereas replication of the Edmonston tag strain recovered
      from cloned DNA was strongly suppressed in its presence. The V protein of the IC
      B strain, but not the Edmonston tag strain, blocked IFN-alpha signalling. The V
      protein of the Edmonston strain from the ATCC also inhibited IFN-alpha
      signalling. There were three amino acid differences between the V proteins of the
      Edmonston ATCC and tag strains, and substitutions of both residues at positions
      110 and 272 were required for the Edmonston ATCC V protein to lose IFN-antagonist
      activity. The P protein of the IC-B strain, which shares the N-terminal 231 aa
      residues with the V protein, also inhibited IFN-alpha signalling. Indeed,
      fragments comprising only those 231 residues of the IC-B and Edmonston ATCC V
      proteins, but not the Edmonston tag V protein, were able to block IFN-alpha
      signalling. However, the N-terminal region of the Edmonston tag V protein, when
      attached to the C-terminal region of the Edmonston ATCC V protein, inhibited IFN
      alpha signalling. Taken together, our results indicate that both the N- and C
      terminal regions contribute to the IFN-antagonist activity of the MV V protein.

PMID- 15448363
TI  - Cell tropism of wild-type measles virus is affected by amino acid substitutions
      in the P, V and M proteins, or by a truncation in the C protein.
AB  - Two nucleotide differences in the P/C/V and M genes between B95a cell- and Vero
      cell-isolated wild-type measles viruses (MV) have previously been found from the
      same patient. The nucleotide difference in the P/C/V gene resulted in an amino
      acid difference (M175I) in the P and V proteins and a 19 aa deletion in the C
      protein. The nucleotide difference in the M gene resulted in an amino acid
      difference (P64H) in the M protein. To verify this result and to examine further
      whether the amino acid difference or truncation is important for MV cell tropism,
      recombinant MV strains containing one of the two nucleotide substitutions, or
      both, were generated. It was found that the P64H substitution in the M protein
      was important for efficient virus growth and dissemination in Vero cells and that
      the M175I substitution in the P and V protein or truncation of the C protein was
      required for optimal growth.

PMID- 15448364
TI  - Relationships and host range of human, canine, simian and porcine isolates of
      simian virus 5 (parainfluenza virus 5).
AB  - Sequence comparison of the V/P and F genes of 13 human, canine, porcine and
      simian isolates of simian virus 5 (SV5) revealed a surprising lack of sequence
      variation at both the nucleotide and amino acid levels (0-3%), even though the
      viruses were isolated over 30 years and originated from countries around the
      world. Furthermore, there were no clear distinguishing amino acid or nucleotide
      differences among the isolates that correlated completely with the species from
      which they were isolated. In addition, there was no evidence that the ability of
      the viruses to block interferon signalling by targeting STAT1 for degradation was
      confined to the species from which they were isolated. All isolates had an
      extended cytoplasmic tail in the F protein, compared with the original W3A and WR
      monkey isolates. Sequence analysis of viruses that were derived from human bone
      marrow cells isolated in London in the 1980s revealed that, whilst they were
      related more closely to one another than to the other isolates, they all had
      identifying differences, suggesting that they were independent isolates. These
      results therefore support previous data suggesting that SV5 can infect humans
      persistently, although the relationship of SV5 to any human disease remains
      highly contentious. Given that SV5 has been isolated on multiple occasions from
      different species, it is proposed that the term simian virus 5 is inappropriate
      and suggested that the virus should be renamed parainfluenza virus 5.

PMID- 15448365
TI  - Gene-gun DNA vaccination aggravates respiratory syncytial virus-induced
      pneumonitis.
AB  - A CD8+ T-cell memory response to respiratory syncytial virus (RSV) was generated
      by using a DNA vaccine construct encoding the dominant Kd-restricted epitope from
      the viral transcription anti-terminator protein M2 (M2(82-90)), linked covalently
      to human beta2-microglobulin (beta2m). Cutaneous gene-gun immunization of BALB/c
      mice with this construct induced an antigen-specific CD8+ T-cell memory. After
      intranasal RSV challenge, accelerated CD8+ T-cell responses were observed in
      pulmonary lymph nodes and virus clearance from the lungs was enhanced. The
      construct induced weaker CD8+ T-cell responses than those elicited with
      recombinant vaccinia virus expressing the complete RSV M2 protein, but stronger
      than those induced by a similar DNA construct without the beta2m gene. DNA
      vaccination led to enhanced pulmonary disease after RSV challenge, with increased
      weight loss and cell recruitment to the lung. Depletion of CD8+ T cells reduced,
      but did not abolish, enhancement of disease. Mice vaccinated with a construct
      encoding a class I-restricted lymphocytic choriomeningitis virus epitope and
      beta2m suffered more severe weight loss after RSV infection than unvaccinated RSV
      infected mice, although RSV-specific CD8+ T-cell responses were not induced.
      Thus, in addition to specific CD8+ T cell-mediated immunopathology, gene-gun DNA
      vaccination causes non-specific enhancement of RSV disease without affecting
      virus clearance.

PMID- 15448366
TI  - Mechanism of cell death during infectious salmon anemia virus infection is cell
      type-specific.
AB  - Infectious salmon anemia virus (ISAV) is a very important fish virus in the
      Northern hemisphere and there is continued interest in understanding the
      mechanisms of its pathogenesis and persistence in fish. In this study, the
      permissive fish cell lines SHK-1, CHSE-214 and TO were used to determine whether
      ISAV-induced cytopathic effect (CPE) is due to apoptosis or necrosis.
      Characteristic apoptotic DNA fragmentation was observed only in ISAV-infected SHK
      1 and CHSE-214 cells. Apoptosis in ISAV-infected SHK-1 cells was confirmed by
      fragment end-labelling assay, suggesting that CPE in these cells is associated
      with apoptosis. ISAV-infected TO cells did not undergo apoptosis, but showed
      leakage of high-mobility group 1 (HMGB1) protein from the nucleus, which is
      characteristic of cells undergoing necrosis; this suggests that CPE in these
      cells is associated with necrosis. ISAV-infected SHK-1 cells did not show leakage
      of HMGB1 protein. Infection with two different strains of ISAV showed that
      induction of apoptosis was correlated with the appearance of CPE in SHK-1 cells.
      ISAV-induced apoptosis was inhibited by a pan-caspase inhibitor, Z-VAD-fmk,
      indicating a caspase-activation pathway. The ISAV putative PB2 protein and
      proteins encoded by RNA segment 7 bound caspase-8 specifically in vitro,
      suggesting that these viral proteins may have a role in ISAV-induced apoptosis.
      These findings demonstrate for the first time that the mechanism of cell death
      during ISAV infection is dependent on the cell type, which may have implications
      for ISAV pathogenesis and persistence.

PMID- 15448367
TI  - Detailed mapping of RNA secondary structures in core and NS5B-encoding region
      sequences of hepatitis C virus by RNase cleavage and novel bioinformatic
      prediction methods.
AB  - There is accumulating evidence from bioinformatic studies that hepatitis C virus
      (HCV) possesses extensive RNA secondary structure in the core and NS5B-encoding
      regions of the genome. Recent functional studies have defined one such stem-loop
      structure in the NS5B region as an essential cis-acting replication element
      (CRE). A program was developed (STRUCTUR_DIST) that analyses multiple rna-folding
      patterns predicted by mfold to determine the evolutionary conservation of
      predicted stem-loop structures and, by a new method, to analyse frequencies of
      covariant sites in predicted RNA folding between HCV genotypes. These novel
      bioinformatic methods have been combined with enzymic mapping of RNA transcripts
      from the core and NS5B regions to precisely delineate the RNA structures that are
      present in these genomic regions. Together, these methods predict the existence
      of multiple, often juxtaposed stem-loops that are found in all HCV genotypes
      throughout both regions, as well as several strikingly conserved single-stranded
      regions, one of which coincides with a region of the genome to which ribosomal
      access is required for translation initiation. Despite the existence of marked
      sequence conservation between genotypes in the HCV CRE and single-stranded
      regions, there was no evidence for comparable suppression of variability at
      either synonymous or non-synonymous sites in the other predicted stem-loop
      structures. The configuration and genetic variability of many of these other NS5B
      and core structures is perhaps more consistent with their involvement in genome
      scale ordered RNA structure, a structural configuration of the genomes of many
      positive-stranded RNA viruses that is associated with host persistence.

PMID- 15448368
TI  - Single point mutation in tick-borne encephalitis virus prM protein induces a
      reduction of virus particle secretion.
AB  - Flaviviruses are assembled to bud into the lumen of the endoplasmic reticulum
      (ER) and are secreted through the vesicle transport pathway. Virus envelope
      proteins play important roles in this process. In this study, the effect of
      mutations in the envelope proteins of tick-borne encephalitis (TBE) virus on
      secretion of virus-like particles (VLPs), using a recombinant plasmid expression
      system was analysed. It was found that a single point mutation at position 63 in
      prM induces a reduction in secretion of VLPs. The mutation in prM did not affect
      the folding of the envelope proteins, and chaperone-like activity of prM was
      maintained. As observed by immunofluorescence microscopy, viral envelope proteins
      with the mutation in prM were scarce in the Golgi complex, and accumulated in the
      ER. Electron microscopic analysis of cells expressing the mutated prM revealed
      that many tubular structures were present in the lumen. The insertion of the prM
      mutation at aa 63 into the viral genome reduced the production of infectious
      virus particles. This data suggest that prM plays a crucial role in the virus
      budding process.

PMID- 15448369
TI  - Evidence of segment reassortment in Crimean-Congo haemorrhagic fever virus.
AB  - The complete nucleotide sequences of the small (S) and medium (M) segments of
      three independent strains of Crimean-Congo haemorrhagic fever (CCHF) virus
      isolated in Uzbekistan, Iraq and Pakistan have been determined. Partial S and M
      segment sequences from two additional strains and partial large segment sequences
      from five strains of CCHF virus have also been obtained. These data have been
      compiled and compared with published full-length and partial sequences of other
      CCHF virus strains. Analysis of virus strains for which complete and partial S
      and M segment sequences are available reveals that the phylogenetic grouping of
      some strains differ between these two segments. Data provided in this report
      suggest that this discrepancy is not the result of recombination, but rather the
      consequence of reassortment events that have occurred in some virus lineages.
      Although described in other genera of the Bunyaviridae family, this is the first
      report of segment reassortment occurring in the Nairovirus genus.

PMID- 15448370
TI  - Analysis of the medium (M) segment sequence of Guaroa virus and its comparison to
      other orthobunyaviruses.
AB  - Guaroa virus (GROV), a segmented virus in the genus Orthobunyavirus, has been
      linked to the Bunyamwera serogroup (BUN) through cross-reactivity in complement
      fixation assays of S segment-encoded nucleocapsid protein determinants, and also
      to the California serogroup (CAL) through cross-reactivity in neutralization
      assays of M segment-encoded glycoprotein determinants. Phylogenetic analysis of
      the S-segment sequence supported a closer relationship to the BUN serogroup for
      this segment and it was hypothesized that the serological reaction may indicate
      genome-segment reassortment. Here, cloning and sequencing of the GROV M segment
      are reported. Sequence analysis indicates an organization similar to that of
      other orthobunyaviruses, with genes in the order GN-NSm-Gc, and mature proteins
      generated by protease cleavage at one, and by signalase at possibly three, sites.
      A potential role of motifs that are more similar to CAL than to BUN virus
      sequences with respect to the serological reaction is discussed. No discernable
      evidence for reassortment was identified.

PMID- 15448371
TI  - Genomic classification of new betanodavirus isolates by phylogenetic analysis of
      the coat protein gene suggests a low host-fish species specificity.
AB  - Viral encephalopathy and retinopathy is a devastating disease that causes
      neurological disorders and high mortality in a large number of cultivated marine
      fish species around the world. It is now established that several viral strains
      classified in the genus Betanodavirus of the family Nodaviridae are the
      aetiological agents of this disease. Betanodaviruses can be classified into four
      genotypes based on the coat protein gene sequence. Here, the coat protein genes
      of the three major strains isolated from sea bass (Dicentrarchus labrax) in
      France were found to be different. In addition, 21 novel strains of betanodavirus
      from several fish species from France, Spain, Tunisia and Tahiti were classified
      by using phylogenetic analysis of a partial sequence (383 nt) of the coat protein
      gene. Most of the isolates were grouped in the red-spotted grouper nervous
      necrosis virus type, which was subdivided into two subtypes, one of them
      containing only French isolates. Furthermore, an isolate obtained from sea bass
      during an outbreak at low temperature (15 degrees C) was classified as the barfin
      flounder nervous necrosis virus type. This is the first reported isolation from
      sea bass of such a strain, which is known to infect several cold-water marine
      fish species. In addition, a betanodavirus belonging to the striped jack nervous
      necrosis virus type was detected in Senagalese sole (Solea senegalensis) farmed
      in Spain, which is the first indication of the presence of this genotype outside
      Japan. These findings suggest that the different genotypes can infect a variety
      of fish species and thus have a low host-fish species specificity.

PMID- 15448372
TI  - Identification of novel HLA-A*0201-restricted CD8+ T-cell epitopes on hepatitis
      delta virus.
AB  - Hepatitis delta virus (HDV) superinfection causes a poor prognosis in hepatitis B
      virus-infected patients and effective therapy is lacking. Cytotoxic T-lymphocyte
      (CTL) responses play an important role in the pathogenesis of chronic viral
      hepatitis; however, the CD8+ T-cell epitopes of HDV have never been defined.
      Potential HLA-A*0201-restricted HDV peptides were selected from the SYFPEITHI
      database and screened by T2 cell-stabilization assay. HLA-A*0201 transgenic mice
      on a C57BL/6 background were injected intramuscularly with an HDV DNA vaccine.
      Splenocytes were stained directly ex vivo with HLA-A*0201-peptide tetramers after
      immunization. Epitope-specific CTL responses were confirmed by cytotoxic assays.
      HLA-A2, chronically infected HDV patients were also enrolled, to assess the
      existence of HDV-specific CD8+ T cells, based on findings in animals. Following
      HDV DNA vaccination, nearly 0.9 % of the total splenic CD8+ T cells were specific
      for peptides HDV 26-34 and HDV 43-51 in HLA-A*0201 transgenic mice, which was
      significantly higher than the number found in non-transgenic mice or in
      transgenic mice that had been immunized with control plasmid. HDV 26-34- and 43
      51-specific CTL lines were able to produce CTL responses to each peptide.
      Interestingly, HDV 26-34- and HDV 43-51-specific CD8+ T cells were also
      detectable in two chronically infected HDV patients in the absence of active HDV
      replication. In conclusion, HDV 26-34 and 43-51 are novel HLA-A*0201-restricted
      CTL epitopes on genotype I HDV. HDV 26-34- and 43-51-specific CTLs have been
      detected in chronic hepatitis delta patients without active disease. Evoking CTL
      responses to HDV may be an alternative approach to controlling HDV viraemia in
      patients with chronic hepatitis delta.

PMID- 15448373
TI  - The glycoprotein of a fish rhabdovirus profiles the virus-specific T-cell
      repertoire in rainbow trout.
AB  - T-cell responses to viruses are still poorly investigated in lower vertebrates.
      In rainbow trout, a specific clonal expansion of T cells in response to infection
      with viral haemorrhagic septicaemia virus (VHSV) was recently identified.
      Expanded T-cell clones expressed a unique 8 aa Vbeta4-Jbeta1 junction (SSGDSYSE)
      in different individuals, reminiscent of a typical public response. To get
      further insight into the nature of this response the modifications of the T-cell
      repertoire following immunization with plasmid expressing the VHSV external
      glycoprotein (G), which is the only protein involved in protective immunity, was
      analysed. After G-based DNA immunization, CDR3-length spectratypes were skewed
      for several Vbeta-Jbeta combinations, including Vbeta4-Jbeta1. In Vbeta4-Jbeta1,
      biases consisted of 6 and 8 aa junctions that were detected from day 52, and were
      still present 3 months after DNA immunization. Sequence analysis of the Vbeta4
      Jbeta1 junctions showed that the 8 aa junction (SSGDSYSE) was clearly expanded,
      indicating that viral G protein was probably the target of the anti-VHSV public
      response. Additional 6 and 8 aa Vbeta4-Jbeta1 junctions were also expanded in G
      DNA-vaccinated fish, showing that significant clonotypic diversity was selected
      in response to the plasmid-delivered G protein. This higher clonotypic diversity
      may be related to the demonstrated higher efficiency of G-based DNA vaccines over
      whole virus immunization. The use of infectious hematopietic necrosis virus
      (IHNV) recombinant viruses, expressing the VHSV G protein, further substantiated
      the VHSV G-protein specificity of the 8 aa Vbeta4-Jbeta1 response and designated
      the 6 aa Vbeta4-Jbeta1 response as potentially directed to a T-cell epitope
      common to VHSV and IHNV.

PMID- 15448374
TI  - Protective humoral responses to severe acute respiratory syndrome-associated
      coronavirus: implications for the design of an effective protein-based vaccine.
AB  - Some of the structural proteins of severe acute respiratory syndrome-associated
      coronavirus (SARS-CoV) carry major epitopes involved in virus neutralization and
      are essential for the induction of protective humoral responses and the
      development of an effective vaccine. Rabbit antisera were prepared using full
      length N and M proteins and eight expressed fragments covering the S protein.
      Antisera to S and M proteins were found to have different neutralizing titres
      towards SARS-CoV infection in vivo, ranging from 1:35 to 1:128. Antiserum to the
      N protein did not contain neutralizing antibodies. Epitopes inducing protective
      humoral responses to virus infection were located mainly in the M protein and a
      region spanning residues 13-877 of the S protein. The neutralizing ability of
      antisera directed against the expressed structural proteins was greater than that
      of convalescent patient antisera, confirming that, as immunogens, the former
      induce strong, SARS-CoV-specific neutralizing antibody responses. The in vitro
      neutralization assay has important implications for the design of an effective,
      protein-based vaccine preventing SARS-CoV infection.

PMID- 15448375
TI  - Expression of tombusvirus open reading frames 1 and 2 is sufficient for the
      replication of defective interfering, but not satellite, RNA.
AB  - Yeast cells co-expressing the replication proteins p36 and p95 of Carnation
      Italian ringspot virus (CIRV) support the RNA-dependent replication of several
      defective interfering (DI) RNAs derived from either the genome of CIRV or the
      related Cymbidium ringspot virus (CymRSV), but not the replication of a satellite
      RNA (sat RNA) originally associated with CymRSV. DI, but not sat RNA, was
      replicated in yeast cells co-expressing both DI and sat RNA. Using transgenic
      Nicotiana benthamiana plants constitutively expressing CymRSV replicase proteins
      (p33 and p92), or transiently expressing either these proteins or CIRV p36 and
      p95, it was shown that expression of replicase proteins alone was also not
      sufficient for the replication of sat RNA in plant cells. However, it was also
      shown that replicating CIRV genomic RNA deletion mutants encoding only replicase
      proteins could sustain replication of sat RNA in plant cells. These results
      suggest that sat RNA has a replication strategy differing from that of genomic
      and DI RNAs, for it requires the presence of a cis-replicating genome acting as a
      trans-replication enhancer.

PMID- 15448376
TI  - ORF6 of Tobacco mosaic virus is a determinant of viral pathogenicity in Nicotiana
      benthamiana.
AB  - Tobacco mosaic virus (TMV) contains a sixth open reading frame (ORF6) that
      potentially encodes a 4.8 kDa protein. Elimination of ORF6 from TMV attenuated
      host responses in Nicotiana benthamiana without alteration in virus accumulation.
      Furthermore, heterologous expression of TMV ORF6 from either potato virus X (PVX)
      or tobacco rattle virus (TRV) vectors enhanced the virulence of both viruses in
      N. benthamiana, also without effects on their accumulation. By contrast, the
      presence or absence of TMV ORF6 had no effect on host response or virus
      accumulation in N. tabacum plants infected with TMV or PVX. TMV ORF6 also had no
      effect on the synergism between TMV and PVX in N. tabacum. However, the presence
      of the TMV ORF6 did have an effect on the pathogenicity of a TRV vector in N.
      tabacum. In three different types of assay carried out in N. benthamiana plants,
      expression of TMV ORF6 failed to suppress gene silencing. Expression in N.
      benthamiana epidermal cells of the encoded 4.8 kDa protein fused to the green
      fluorescent protein at either end showed, in addition to widespread cytosolic
      fluorescence, plasmodesmatal targeting specific to both fusion constructs. The
      role of the ORF6 in host responses is discussed.

PMID- 15448377
TI  - Functional analysis of the Cucumber mosaic virus 2b protein: pathogenicity and
      nuclear localization.
AB  - The 2b protein encoded by Cucumber mosaic virus (CMV) has been shown to be a
      silencing suppressor and pathogenicity determinant in solanaceous hosts, but a
      movement determinant in cucumber. In addition, synergistic interactions between
      CMV and Zucchini yellow mosaic virus (ZYMV) have been described in several
      cucurbit species. Here, it was shown that deletion of the 2b gene from CMV
      prevented extensive systemic movement of the virus in zucchini squash, which
      could not be complemented by co-infection with ZYMV. Thus, ZYMV expressing a
      silencing suppressor with a different target could not complement the CMV 2b
      specific movement function. Expression of the 2b protein from an attenuated ZYMV
      vector resulted in a synergistic response, largely restoring infection symptoms
      of wild-type ZYMV in several cucurbit species. Deletion or alteration of either
      of two nuclear localization signals (NLSs) did not affect nuclear localization in
      two assays, but did affect pathogenicity in several cucurbit species, whilst
      deletion of both NLSs led to loss of nuclear localization. The 2b protein
      interacted with an Arabidopsis thaliana karyopherin alpha protein (AtKAPalpha) in
      the yeast two-hybrid system, as did each of the two single NLS-deletion mutants.
      However, 2b protein containing a deletion of both NLSs was unable to interact
      with AtKAPalpha. These data suggest that the 2b protein localizes to the nucleus
      by using the karyopherin alpha-mediated system, but demonstrate that nuclear
      localization was insufficient for enhancement of the 2b-mediated pathogenic
      response in cucurbit hosts. Thus, the sequences corresponding to the two NLSs
      must have another role leading to pathogenicity enhancement.

PMID- 15448378
TI  - Selection pressures in the capsid genes of plant RNA viruses reflect mode of
      transmission.
AB  - To determine the selection pressures faced by RNA viruses of plants, patterns of
      nonsynonymous (dN) and synonymous (dS) substitution in the capsid genes of 36
      viruses with differing modes of transmission were analysed. This analysis
      provided strong evidence that the capsid proteins of vector-borne plant viruses
      are subject to greater purifying selection on amino acid change than those
      viruses transmitted by other routes and that virus-vector interactions impose
      greater selective constraints than those between virus and plant host. This could
      be explained by specific interactions between capsid proteins and cellular
      receptors in the insect vectors that are necessary for successful transmission.
      However, contrary to initial expectations based on phylogenetic relatedness,
      vector-borne plant viruses are subject to weaker selective constraints than
      vector-borne animal viruses. The results suggest that the greater complexity
      involved in the transmission of circulative animal viruses compared with non
      circulative plant viruses results in more intense purifying selection.

PMID- 15448379
TI  - Maternal transmission studies of BSE in sheep.
AB  - If BSE (bovine spongiform encephalopathy) infected the UK sheep population
      concurrently with cattle, it would only now be maintained by transmission between
      sheep by routes which could include from mother to lamb either in utero or via
      perinatal close contact. In this study of experimental BSE, Cheviot ewes
      challenged orally with BSE cattle brain produced lambs of various PrP genotypes
      over the next 7 years. Of 72 surviving to >30 months of age, 29 are of the most
      susceptible PrP genotype (AQ/AQ) and born to mothers that were challenged with
      BSE. None of the progeny have shown any signs of disease. The results suggest
      that in these sheep, BSE could only transmit by the maternal route at a frequency
      of less than one in four (95 % confidence limit) from clinically affected ewes, a
      rate which if replicated in other breeds may not be sufficient to maintain BSE
      within the sheep population.

PMID- 15448380
TI  - Low frequency of the scrapie resistance-associated allele and presence of lysine
      171 allele of the prion protein gene in Italian Biellese ovine breed.
AB  - Frequencies of polymorphisms at codons 136, 154 and 171 of the prion protein
      (PrP) gene were studied in 1207 pure-bred and cross-bred Italian Biellese rams, a
      small ovine breed of about 65 000 head in Italy. Aside from the five most common
      alleles (VRQ, ARQ, ARR, AHQ and ARH), the rare ARK allele was also found, with
      the highest frequency reported so far in an ovine breed (2.5 %). ARK/---
      genotypes had a total frequency of 4.9 %. The resistance-associated ARR allele
      was seen at a low frequency (8.3 %). Only 1.4 % of animals examined had a
      resistant ARR/ARR PrP genotype. Semi-resistant (ARR/ARQ, ARR/ARH and ARR/AHQ) PrP
      genotypes had a total frequency of 12.6 % and PrP genotypes that are associated
      with high scrapie susceptibility (e.g. VRQ/VRQ and ARQ/ARQ) had a total frequency
      of 81.1 %. Statistical analysis comparing PrP allele frequencies between pure
      bred and cross-bred animals showed that the ARR allele occurred at a
      significantly lower frequency in pure-bred rams. Furthermore, comparison of PrP
      allele frequencies between pure-bred rams over 18 months of age and those below
      18 months of age showed a significant decrease in the ARR allele in breeding rams
      over 18 months of age. Based on these results, breeding for scrapie resistance in
      the Biellese breed will have to take into account the low frequency of the ARR
      allele, which also seems to be subject to negative selection by farmers. Further
      investigation is required to understand whether the ARK allele is also associated
      with resistance to transmissible spongiform encephalopathies.

PMID- 15448381
TI  - Abstracts of the 28th National Congress of the Italian Association for the Study
      of the Pancreas (AISP). Verona, Italy. October 28-30, 2004.

PMID- 15448382
TI  - Profile of iodine content of salt and urinary iodine excretion levels in selected
      districts of Tamil Nadu.
AB  - OBJECTIVE: Iodine deficiency disorders (IDD) is the most common cause of
      preventable mental retardation in world today. Out of 29 districts in Tamil Nadu,
      24 have been surveyed and all have been found to be endemic to IDD. There is a
      complete ban on the sale of non iodised salt in the state since 1995. The present
      study was conducted to assess the iodine content of salt and urinary iodine
      excretion levels amongst the beneficiaries in the state to help the government to
      strengthen the existing Universal salt iodisation (USI) programme activities.
      METHODS: The study was undertaken in 24 districts of Tamil Nadu during the year
      2001. The guidelines recommended by WHO/UNICEF/ICCIDD for a rapid assessment of
      salt iodisation in a district was adopted. A minimum of 150 salt samples were
      collected from each district by utilising the uniform sampling methodology. The
      iodine content of salt samples was analysed using the standard iodometric
      titration method. At least 60 children from each school were randomly selected
      and were requested to provide "on the spot" casual urine samples. The urinary
      iodine excretion (UIE) levels were analysed using the wet digestion method.
      RESULTS: It was observed that 62.3% of the families were consuming iodised salt
      with more than 5 ppm of iodine. It was found that district Perambalour had
      deficient iodine nutriture as revealed by the median UIE levels less than 100
      micro g/l. CONCLUSION: The findings of the present study reveals the success of
      USI programme and highlights need for continued monitoring of the quality of salt
      provided to the population in order to achieve the goal of IDD elimination.

PMID- 15448384
TI  - Sickle cell disease in central India.
AB  - OBJECTIVE: The incidence and the risk factors of sickle cell disease (SCD),
      vaccinated with Pneumococcal vaccine and on penicillin prophylaxis has not been
      previously reported in India. METHODS: This prospective hospital based study
      followed 325 children on penicillin prophylaxis, of which 161 were vaccinated for
      pneumococci, over 146.84 person years to determine the incidence and determinants
      of crisis (SCC) and infections. The average age at presentation was 7.05 +/- 3.26
      years with male preponderance below 2 years. RESULTS: The main causes for
      hospitalizations were for blood transfusion, SCC and infections. The incidence of
      SCC was 1.25 per patient per year and that of infection was 1.38 per person per
      year. The risk factors for SCC were Mahar caste (p = 0.007) non-compliance (p =
      0.000) and protein energy malnutrition (PEM) (p = 0.0015) and for infection were
      also PEM (p = 0.023), Mahar caste (p = 0.021) and noncompliance (p = 0.001).
      CONCLUSION: Malnutrition and non-compliance with medication increased the
      patient's susceptibility to SCC and infections.

PMID- 15448385
TI  - Temperature monitoring in newborns using thermospot.
AB  - OBJECTIVE: Hypothermia is a common problem in newborns. This is more so in
      community environment especially in low-birth weight and preterm babies. METHODS:
      A simple liquid crystal temperature monitoring device was used in 20 infants on a
      continuous basis to monitor for hypothermia. This was compared with the
      measurement of rectal temperature using a rectal thermometer. The colour changes
      and measures to be taken when hypothermia occurs was explained to the mothers and
      was well understood by all. RESULTS: The Thermo Spot was in agreement with the
      rectal temperature in 310 out of 313 measurements. This includes 299 times when
      temperature was normal; and 11 times when the temperature was hypothermic. It
      underestimated the temperature of three infants, falsely indicating hypothermia
      in a normothermic child with normal body temperature. It correctly identified
      hypothermia in every case. CONCLUSION: ThermoSpot device is a simple accurate
      device allowing continuous thermal monitoring of low birth weight infants,
      especially in resource poor setting.

PMID- 15448386
TI  - Reproductive health awareness of school-going, unmarried, rural adolescents.
AB  - OBJECTIVE: In 1996, India included Adolescent Health in Reproductive and Child
      Heatlh Programme. This Task-Force Study was planned to test the awareness level
      of adolescents regarding various reproductive health issues and to identify
      lacunae in knowledge, particularly in legal minimum age of marriage, number of
      children, male preference, contraceptive practices, about STIs /AIDS etc.
      METHODS: It was a multicentre study, done in rural co-education/higher secondary
      schools of 22 districts located in 14 states through Human Reproductive Research
      Centre (HRRC's) of the Indian Council of Medical Research (ICMR). A sample of
      8453 school going adolescents (aged 10-19 years) was surveyed by means of open
      ended, self-administered questionnaires maintaining confidentiality. RESULTS:
      Mean age of adolescents was 14.3 +/- 3.4 years. Awareness of legal minimum age of
      marriage was present in more than half of adolescents. Attitude towards marriage
      beyond 21 years in boys and 18 years in girls was favorable. Mean number of
      children desired was 2.2 +/- 1.4. However, number of children desired by boys
      (2.2+/-1.6) was significantly more (p< 0.000) than those desired by girls (2.0+/
      1.1). More boys (23.7%) than girls (9.4%) wanted three or more children with male
      preference. Only 19.8% of adolescents were aware of at least one method of
      contraception. Only two-fifth (39.5%) were aware of AIDS and less than one-fifth
      (18%) were aware of STDs and most of them thought it is same as AIDS. Awareness
      of at least one method of immunization was present in three-fifth (60.1%) of
      students. It was least for DPT (13.5%) and most (55%) were aware of polio only.
      Awareness of all Reproductive Health matters was more in boys than girls and more
      in late teens (15-19) than earlier teens (10-14). CONCLUSION: The study showed
      tremendous lacunae in awareness of all Reproductive Health (RH) matters. There is
      a need for evolving information, education, and communication strategies to focus
      on raising awareness on RH and gender related issues. A sociocultural research is
      needed to find the right kind of sexual health services for young girls and boys.

PMID- 15448387
TI  - Hyponatremia in hospitalized critically ill children: current concepts.
AB  - Hyponatremia (serum sodium to < 136 mEq/l) is the most common electrolyte
      abnormality in critically ill children. It could result from a deficit of sodium,
      or surplus of water. Impaired water excretion, 'inappropriate' release of
      vasopressin, use of hypotonic fluids, redistribution of sodium and water, sick
      cell syndrome, several drugs and primary illness all may contribute to
      hyponatremia. Acute hyponatremia, defined as a fall in serum sodium to ~ 120
      mEq/l within 48 hours may result in acute cerebral edema and brain stem
      herniation particularly in children. However, there is paucity of data on
      hyponatremia in hospitalized critically ill patients. Studies addressing
      incidence, cause and outcome of hyponatremia in critically ill patients are
      needed to plan rational fluid therapy protocols, and resolve the current debate,
      which calls for abandonment of N/5 saline in 5% dextrose solution as maintenance
      intravenous fluid in favour of normal saline to prevent hyponatremia. At present
      it is not fully correct to assume that isotonic maintenance fluids would be
      superior to current maintenance fluids. Reducing the volume of maintenance fluid
      to about 75% of normal maintenance volume may be more appropriate way to prevent
      hyponatremia in view of water retaining effect of high ADH and reduced renal free
      water clearance in critically ill children.

PMID- 15448388
TI  - Montelukast - evaluation in 6 to 14 years old children with persistent asthma -
      pediatric montelukast study group.
AB  - OBJECTIVE: The suffering of children with asthma as a persistent illness is
      present in approximately 10% of the total population. The prevalent treatment
      regimens available has been the inhaled coticosteroids and short acting
      bronchodialators. Though the therapies are rational and well accepted but at the
      cost of side effects on chronic use. The changing definitions and guidelines with
      regard to asthma have given a classified slot to newer treatments like
      leukotriene receptor antagonists (LTRAs). The aim of the present study was to
      study the efficacy and tolerability of montelukast in the treatment of Indian
      pediatric patients aged 6 to 14 years with chronic asthma. METHODS: It was a
      prospective, open, non-comparative multicentric study. 881 Children (Mean age
      11.83+/- 3.12 years) were included. Patients fulfilling the inclusion criteria
      were given one mouth dissolving 5 mg montelukast tablet daily in the evening for
      30 days. RESULTS: There was an overall improvement in all the efficacy
      parameters. The daytime total asthma score decreased from 9.55 +/- 1.52 to 3.59
      +/- 2.10. The average number of asthma attacks over the last 4 weeks decreased
      from 1.14+/- 1.19 to 0.28+/-0.57. The number of nocturnal awakenings fell from
      1.54+/-0.78 to 0.43+/-0.54. FEV1 (L) [Predicted] improved by 21.18%). PEFR
      (L/min.) improved by 34.69%). Approximately 45% physicians rated the treatment as
      excellent, 30% as very good, 18% as good, 7% as fair and none as poor.
      CONCLUSION: Montelukast administered once daily improved efficacy end-points and
      was well tolerated in pediatric patients with chronic persistent asthma
      establishing itself as a valuable treatment option to current asthma therapies in
      6 to 14 years old patients.

PMID- 15448389
TI  - Disease management by protocol - rules of the game.

PMID- 15448390
TI  - Management of septic arthritis.
AB  - Septic arthritis in children remains a serious disease with the potential for
      significant systemic and musculoskeletal morbidity. Staphlococcus aureus is the
      most common cause of bone and joint infections in all age groups. Microbial
      invasion of the synovial space occurs typically results from hematogenous
      seeding. Diagnosis in neonates and young infants can be difficult since the
      clinical signs are much less specific in these age groups. Early diagnosis by
      needle aspiration of the affected joint and prompt initiation of appropriate
      antimicrobial therapy in conjunction with drainage of the affected joint is
      critical to avoid destruction of the articular cartilage and prevent disability.
      Septic arthritis in infants and children should always be managed by a
      pediatrician in close consultation with an orthopedic surgeon. Empiric antibiotic
      regimens should always include adequate anti-staphylococcal coverage. Antibiotic
      treatment should be started with appropriate doses of intravenous antibiotics.
      Switch to oral antibiotic therapy can be made when patient demonstrates clinical
      improvement. A minimum of 3-4 weeks of therapy is recommended. Close follow-up is
      warranted to monitor the growth of the affected limb until skeletal maturity.

PMID- 15448391
TI  - Optimum management of pediatric patients with fever and neutropenia.
AB  - Fever with neutropenia is a common clinical problem in patients receiving cancer
      treatment. Prevention and optimum management of infectious complications is
      critical to the overall success of cancer therapy. This article provides an
      overview of the current status of this evolving subject. While the basic
      principles of rapid institution of broad spectrum antibiotics, early intervention
      with empiric antifungal therapy and continuation of antimicrobials during period
      of risk are unlikely to change, there is increasing interest in titrating this
      aggressive approach based on the projected risk of the development of a serious
      invasive infection. Oral antibiotic therapy and outpatient management are
      currently being studied in pediatric oncology patients, but even when successful
      these alternatives to the traditional "in hospital, parenteral antibiotic
      therapy" approach are unlikely to be applicable in all patient populations and
      clinical settings. While there is no replacement for clinical acumen and careful
      monitoring, judicious use of diagnostic resources such as blood cultures and
      imaging studies is a key component of optimum care. Selection of empiric
      antibiotics based on ongoing monitoring of antimicrobial susceptibility patterns
      is emphasized.

PMID- 15448392
TI  - Treatment of invasive Aspergillosis in children with hematologic malignancies.
AB  - The respiratory tract is the most common organ involved with Aspergillosis in
      children with hematologic malignancies. Also Aspergillus species tend to invade
      blood vessels resulting in systemic dissemination to multiple organs. Early
      diagnosis and treatment are pivotal to the patient's outcome. A high index of
      suspicion should be maintained in children who have profound neutropenia and
      present with prolonged fever that is unresponsive to systemic antibiotics.
      Several diagnostic modalities should be used simultaneously in order to confirm
      the diagnosis in an expedited manner. Combination and sequential antifungal
      therapy have been shown to be of added benefit. Surgical intervention is
      associated with a high mortality rate, but may be indicated in children with a
      localized disease. In this article the authors review the epidemiology,
      microbiology, pathology, and clinical manifestations of invasive aspergillosis in
      children with hematologic malignancies. Current diagnostic approach, medical, and
      surgical treatment options are discussed.

PMID- 15448393
TI  - Management of pelvic inflammatory disease in adolescents.
AB  - Pelvic inflammatory disease (PID) is highly prevalent among sexually active
      adolescent females. The major organisms are N gonorrhoeae and C trachomatis.
      Diagnosis is based on historical information and clinical findings. Early
      diagnosis and treatment effectively reduce the incidence of complications
      associated with PID. Highly effective treatment regimens are available and main
      antimicrobials used include quinolones, cephalosporins, metronidazole,
      doxycycline, and azithromycin. Delay or inadequate treatment is associated with
      long term sequelae including tubal infertility and chronic pelvic pain.
      Prevention efforts should be directed towards routine screening and treatment for
      sexually transmissible infections, public education and provision of resources
      for treatment and follow-up.

PMID- 15448394
TI  - Bronchial foreign bodies.
AB  - Foreign body aspiration is an extremely serious problem in childhood with varied
      clinical presentation demanding high degree of suspicion on the part of
      clinician. Surgical emphysema of the neck and chest often complicates
      tracheostomy and sharp penetrating injuries to the neck perforating viscera of
      the aerodigestive tract. Rarely if follows chest injuries. But emphysema due to
      the neck of foreign bodies in the bronchus is quite rare. The authors hereby
      report four cases of surgical emphysema following foreign body aspiration into
      the tracheobronchial tree.

PMID- 15448395
TI  - Neurofibromatosis type I: spinal neoplasia without symptoms.
AB  - Neurofibromatosis1 (NF-1) or von Recklinghausen disease is the most common of the
      neurocutaneous syndromes. It is characterized by presence of hamartomas in
      multiple organs. Inheritance is autosomal dominant but spontaneous mutations are
      seen in half the cases. The authors are reporting a classical case of this
      syndrome with spinal neoplasia which was interestingly asymptomatic. Authorities
      seem to agree that because the risk of developing intradural disease is
      significant in patients with NF-1, a routine MRI of the entire spine should be
      obtained.

PMID- 15448396
TI  - Kabuki make-up syndrome.
AB  - Kabuki make-up syndrome is a rare disorder characterized by mental retardation,
      postnatal dwarfism and peculiar facies. This condition is believed to be common
      in Japan, but has been reported from other parts of the world. The authors report
      a case of this syndrome in an eight-year-old girl, with the characteristic
      findings from India.

PMID- 15448397
TI  - Bulimia nervosa.
AB  - Although there is a lot of information coming up to explain the pathogenesis of
      anorexia nervosa, yet little is know about bulimia nervosa in Indian literature.
      This case report highlights the typical presentation of a case of bulimia nervosa
      in an adolescent girl, where bulimia symptoms were preceded by anorexic behavior.
      Our case showed clinical similarity with the diagnostic criteria of the available
      classification system. The absence of self-evaluation for body weight and shape
      in this case be explained on the basis of cultural factors. To some extent,
      initial anorexic behavior could have played a role in etiopathogenesis of bulimia
      nervosa.

PMID- 15448398
TI  - Surgical nonbilious vomiting.

PMID- 15448399
TI  - Post exposure hepatitis B vaccination.

PMID- 15448401
TI  - Surface treatments and roughness properties of Ti-based biomaterials.
AB  - Nowadays, the use of implanted devices is a well-acknowledged practice in the
      field of orthopaedic and dental surgery. Scientific research and clinical
      experience suggest that the successful exploitation of these devices mainly
      depends on osseointegration, considered as both anatomical congruency and load
      bearing capacity. Indeed, the osseointegration process is influenced by a wide
      range of factors: anatomical location, implant size and design, surgical
      procedure, loading effects, biological fluids, age and sex, and, in particular,
      surface characteristics. For this reason, several attempts have been aimed at
      modifying implant surface composition and morphology to optimise implant-to-bone
      contact and improve integration. Preliminary interactions between implanted
      materials and biological environment are deemed to be governed by the surface
      properties; they control the amount and quality of cell adhesion on the surface
      and, consequently, cell/tissue growth. Thus, surface properties govern new bone
      tissue formation and implant osseointegration. This paper reviews the state of
      art in the field of physical, chemical and biochemical treatments commonly used
      on Ti-based biomaterials for the production of biomedical devices. In particular,
      roughness characteristics due to physical and chemical techniques are
      investigated; the development of biologically active surfaces by means of
      biochemical functionalisation is also considered.

PMID- 15448402
TI  - Factors having influence on the rheological properties of Ti6A14V slurry.
AB  - A highly porous Ti6Al4V could be produced with a porous polymeric sponge and
      Ti6Al4V slurry. However, the rheological properties of Ti6Al4V slurry appeared to
      be the key issue in the preparation of porous Ti6Al4V. In this study, factors
      having influence on the rheological properties of Ti6Al4V slurry were addressed
      in detail. Ti6Al4V powders, organic thickening agents (binders), dispersants,
      concentration of powder and pH values were optimised with regard to the
      rheological properties of Ti6Al4V slurry. The results show that Ti6Al4V powder
      with a mean diameter of 45 microm and spherical shape is beneficial for the
      preparation of Ti6Al4V slurry. Meanwhile binders with two ingredients, which
      decompose at different temperatures, have the advantage to keep the shape after
      debinding. The optimised procedure, based on the findings, made it possible to
      produce highly porous Ti6Al4V with reticulate porous structure. Porous Ti6Al4V
      produced by this way is expected to be a promising biomaterial for tissue
      engineering scaffolds and orthopaedic implant applications.

PMID- 15448403
TI  - Phase and microstructural development in alumina sol-gel coatings on CoCr alloy.
AB  - Phase transformation of gamma-Al(2)O(3) to alpha-Al(2)O(3) in alumina sol gel
      coatings on biomedical CoCr alloy was studied as function of heat treatment
      temperature and time. Transformation in unseeded coatings was significant only
      above approximately 1200 degrees C. Addition of alpha-Al(2)O(3) seed particles
      having an average size of approximately 40 nm lowered the phase transformation
      temperature to around 800 degrees C. These particles were considered to act as
      heterogeneous nucleation sites for epitaxial growth of the alpha-Al(2)O(3) phase.
      The kinetics and activation energy (420 kJ/mol) for the phase transformation in
      the seeded coatings were similar to those reported for seeded monolithic alumina
      gels indicating that the transformation mechanism is the same in the two material
      configurations. Avrami growth parameters indicated that the mechanism was
      diffusion controlled and invariant over the temperature range studied but that
      growth was possibly constrained by the finite size of the seed particles and/or
      coating thickness. The phase transformation occurred by the growth of alpha
      Al(2)O(3) grains at the expense of the precursor fine-grained gamma-Al(2)O(3)
      matrix and near-complete transformation coincided with physical impingement of
      the growing grains. The grain size at impingement was approximately 100 nm which
      agreed well with that predicted from the theoretical linear spacing of seed
      particles in the initial sol.

PMID- 15448404
TI  - The formation of a hydroxyl bond and the effects thereof on bone-like apatite
      formation on a magnesia partially stabilized zirconia (MgO-PSZ) bioceramic
      following CO2 laser irradiation.
AB  - For the purpose of improving the bioactivity of a magnesia partially stabilized
      zirconia (MgO-PSZ) and to explore a new technique for inducing OH group and
      apatite formation, a CO(2) laser has been used to modified the surface
      properties. The bioactivity of the CO(2) laser modified MgO-PSZ has been
      investigated in stimulated human fluids (SBF) with ion concentrations almost
      equal to those in human blood plasma. Some hydroxyl groups were found on the MgO
      PSZ following CO(2) laser treatment with selected power densities. The surface
      melting on the MgO-PSZ induced by CO(2) laser processing provides the Zr(4+) ion
      and OH(-) ion, in turn, the incorporation of the Zr(4+) ion and the OH(-) ion
      creates the Zr-OH group on the surface. After 14 days of SBF soaking, the
      apatites formed on the MgO-PSZ with relatively high amount of hydroxyl groups
      generated by the CO(2) laser treatment, while no apatite was observed on the
      untreated with few hydroxyl groups. It exhibits that the Zr-OH groups on the MgO
      PSZ surface is the functional groups to facilitate the apatite formation. The
      increased surface roughness provides more active sites, meantime, increased
      surface energy benefits to the adsorption and reaction on the surface.

PMID- 15448405
TI  - Assessment of wear on the cones of modular stainless steel Exeter hip stems.
AB  - The wear on the stem cones of retrieved Exeter Universal hip stems has been
      assessed using scanning electron microscopy (SEM), energy-dispersive X-ray
      analysis (EDX) and surface profilometry. The in-service life of these prosthetic
      stems varied, up to a maximum of 7 years. A combination of SEM, EDX and visual
      assessment indicates that the stem cones have not suffered from any corrosion.
      SEM scans indicate that damage to stem cones (excluding extraction and post
      removal damage) can be categorised into insertion marks and fretting marks. In
      some cases there are signs of material being deposited on the cone surface.
      Surface profilometry suggests that the levels of debris generation at the
      cone/internal head interface are very low relative to those that are likely to be
      associated with head articulation against the acetabular cup. A total of 20 stem
      cones underwent SEM scans. From these, 10 subsequently have undergone surface
      profilometry along with the corresponding internal head surfaces. There is a good
      correlation between surface roughness measured by surface profilometry and the
      topography observed in the SEM images. The surface roughness of each stem cone is
      similar to that of the corresponding internal head surface.

PMID- 15448406
TI  - Sol-gel synthesis, structure and bioactivity of polycaprolactone/CaO . SiO2
      hybrid material.
AB  - A method has been developed to cast novel organic/inorganic polymer hybrids from
      multicomponent solutions containing tetramethyl orthosilicate, calcium nitrate
      tetrahydrate, polycaprolactone, water, and methylethyketone via sol-gel process.
      The existence of the hydrogen bonds between organic and inorganic components of
      the hybrid and hydroxyapatite formation on the surface was proved by Fourier
      transform infrared analysis. The morphology of the hybrid material was studied by
      scanning electron microscopy. The structure of a molecular level dispersion was
      disclosed by atomic force microscopy, pore size distribution, and surface
      measurements. The infrared spectra of the hybrid relative to sample soaked in a
      fluid simulating the composition of human blood plasma suggests that
      polycaprolactone/CaO * SiO(2) hybrid material synthesised via sol-gel process is
      bioactive as well as the CaO * SiO(2) gel glass.

PMID- 15448407
TI  - Bioactivity of ceramic-polymer composites with varied composition and surface
      topography.
AB  - HAPEX trade mark (40 vol % hydroxyapatite in a high-density polyethylene matrix)
      and AWPEX (40 vol % glass-ceramic apatite-wollastonite in a high-density
      polyethylene matrix) are composites designed to provide bioactivity and to match
      the mechanical properties of human cortical bone. HAPEX trade mark has had
      clinical success in middle ear and orbital implants, and there is great potential
      for further orthopaedic applications of these materials. However, more detailed
      in vitro investigations must be performed to better understand the biological
      interactions of the composites. In this study, the bioactivity of each material
      was assessed. Specifically, the effects of controlled surface topography and
      ceramic filler composition on apatite layer formation in acellular simulated body
      fluid (SBF) with ion concentration similar to those of human blood plasma were
      examined. Samples were prepared as 1 x 10 x 10 mm(3) tiles with polished,
      roughened or parallel-grooved surface finishes, and were incubated in 20 ml of
      SBF at 36.5 degrees C for one, three, seven or 14 days. The formation of an
      apatite layer on the composite surface after immersion was demonstrated by thin
      film X-ray diffraction, environmental scanning electron microscopy and energy
      dispersive X-ray analysis. Variations in sample weight and solution pH over the
      period of incubation were also recorded. Significant differences were found
      between the two materials tested, with greater bioactivity in AWPEX than HAPEX
      trade mark. Results also showed surface topography to be important, with rougher
      samples correlated to earlier apatite formation. Osteoblast-like cells
      proliferated favourably on both composite materials, with many filopodia
      connections, preferential attachment to ceramic particles and contact guidance
      effects evident.

PMID- 15448408
TI  - Apatite-forming ability of alginate fibers treated with calcium hydroxide
      solution.
AB  - Calcium alginate fibers were prepared by extruding an aqueous sodium alginate
      solution into an aqueous calcium chloride solution. The fibers were treated with
      a saturated aqueous calcium hydroxide solution for various periods and their
      apatite-forming ability was examined in a simulated body fluid (SBF). The calcium
      alginate fibers were treated with the aqueous calcium hydroxide solution for
      periods longer than five days formed apatite on their surfaces in SBF, and their
      apatite-forming ability improved with increasing calcium hydroxide treatment
      time. The amount of calcium ions released from the fibers also increased with
      increasing calcium hydroxide treatment time, resulting in acceleration of
      nucleation and growth of apatite on the fiber surfaces. The resultant apatite
      alginate fiber composite is expected to be useful as a flexible bioactive bone
      repairing material.

PMID- 15448409
TI  - Mechanical behavior of bioactive composite cements consisting of resin and glass
      ceramic powder in a simulated body fluid: effect of silane coupling agent.
AB  - Time-dependent strength behavior was investigated for bisphenol-a-glycidyl
      methacrylate/triethylene glycol dimethacrylate (Bis-GMA/TEGDMA) resin cements
      combined with glass-ceramic A-W filler treated with various kinds of silane
      coupling agents. The fracture strength of the composite resin cements was
      measured by three-point bending as a function of stressing rate in a simulated
      body fluid (SBF), and thereby the stress-corrosion susceptibility constant was
      evaluated. The fracture strength was found to depend on the kind of coupling
      agent used. For the present Bis-GMA/TEGDMA resin, the silane coupling agents
      without hydrophilic amine groups can be used to obtain good adhesion between
      resin and A-W filler owing to their nature of co-polymerizing with the resin. On
      the other hand, all the composite resin cements showed nearly the same degree of
      stress-corrosion susceptibility whether the A-W fillers were treated or untreated
      with silane coupling agents. This means that the stress-corrosion susceptibility
      of the present composite cements is predominantly affected by that of the matrix
      resin. Thus, the microcrack formation and growth at the resin matrix near
      particle - resin interface were thought to determine overall time-dependent
      strength behavior of the composite cements.

PMID- 15448410
TI  - Formation of highly adherent nano-porous alumina on Ti-based substrates: a novel
      bone implant coating.
AB  - Thin, nano-porous, highly adherent layers of anodised aluminium formed on the
      surface of titanium alloys are being developed as coatings for metallic surgical
      implants. The layers are formed by anodisation of a 1-5 microm thick layer of
      aluminium which has been deposited on substrate material by electron beam
      evaporation. The surface ceramic layer so produced is alumina with 6-8 wt %
      phosphate ions and contains approximately 5 x 10(8) cm(-2) pores with a
      approximately 160 nm average diameter, running perpendicular to the surface.
      Mechanical testing showed the coatings' shear and tensile strength to be at least
      20 and 10 MPa, respectively. Initial cell/material studies show promising
      cellular response to the nano-porous alumina. A normal osteoblastic growth
      pattern with cell number increasing from day 1 to 21 was shown, with slightly
      higher proliferative activity on the nano-porous alumina compared to the
      Thermanox control. Scanning electron microscopy (SEM) examination of the cells on
      the porous alumina membrane showed normal osteoblast morphology. Flattened cells
      with filopodia attaching to the pores and good coverage were also observed. In
      addition, the pore structure produced in these ceramic coatings is expected to be
      suitable for loading with bioactive material to enhance further their biological
      properties.

PMID- 15448411
TI  - Titanium oxide nanotubes for bone regeneration.
AB  - Titanium oxide nanotubes with Ca ions on their surfaces were prepared as 2 mm
      cylindrical inserts and placed into surgically created bone defects in the femurs
      of Wistar rats. On day 3, fibroblast-like cells were present on the surface of
      the nanotube inserts and fibers were observed by scanning electron microscopy
      (SEM). On day 7, cells with alkaline phosphatase activity were present and
      identified as osteoblasts by SEM and transmission electron microscopy. New bone
      matrices were observed in and around the porous nanotube inserts by light
      microscopy. Compared with clinically used hydroxyapatite and tricalcium
      phosphate, beta-titanium oxide nanotubes promote faster acquisition and
      development of osteoblasts and bone tissues and have better bone regenerating
      ability after one week.

PMID- 15448412
TI  - Flexural properties of crosslinked and oligomer-modified glass-fibre reinforced
      acrylic bone cement.
AB  - The flexural properties of oligomer-modified bone cement with various quantities
      of crosslinking monomer with or without glass fibre reinforcement were studied.
      The flexural strength and modulus of acrylic bone cement-based test specimens
      (N=6), including crosslinked and oligomer-modified structures with or without
      glass fibres, were measured in dry conditions and after immersion in simulated
      body fluid (SBF) for seven days (analysis with ANOVA). One test specimen from the
      acrylic bone cement group containing 30 wt % crosslinking monomer of its total
      monomer content was examined with scanning electron microscope (SEM) to evaluate
      signs of the semi-interpenetrating polymer network (semi-IPN). The highest dry
      mean flexural strength (130 MPa) was achieved with the bone cement/crosslinking
      monomer/glass fibre combination containing 5 wt % crosslinking monomer of its
      monomer content. The highest flexural modulus (11.5 GPa) was achieved with the
      bone cement/crosslinking monomer/glass fibre combination containing 30 wt %
      crosslinking monomer of its monomer content. SBF storage decreased the flexural
      properties of the test specimens, as did the addition of the oligomer filler.
      Nevertheless, the addition of crosslinking monomer and chopped glass fibres
      improves considerably the mechanical properties of oligomer-modified (i.e.
      porosity-producing filler containing) acrylic bone cement. In addition, some
      signs of the semi-IPN structure were observed by SEM examination.

PMID- 15448413
TI  - In vitro and in vivo performance of Ti6Al4V implants with plasma-sprayed
      osteoconductive hydroxylapatite-bioinert titania bond coat "duplex" systems: an
      experimental study in sheep.
AB  - To evaluate the in vivo performance of "duplex" hydroxylapatite top coat/TiO(2)
      bond coat systems, cylindrical Ti6Al4V rods of 130 mm in length and 11-13 mm in
      diameter were coated by atmospheric plasma spray (APS) technique with both a
      standard hydroxylapatite (HAp) layer and a HAp+TiO(2) bond coat "duplex" layer.
      In this pilot study coated and uncoated rods serving as controls were implanted
      into the femur of sheep so that their distal ends were freely suspended in the
      medulla of the femur. After an observation time of six months it was found that
      bone apposition and bone ingrowth were considerably increased in the presence of
      a osteoconductive coating. In particular, in vivo spalling and delamination
      frequently observed with HAp coatings was virtually absent in duplex coatings
      owing to the strong adhesion of the bond coat to the HAp top coat that anchored
      the latter solidly to the metallic surface of the implant. Some tentative
      mechanisms leading to this improved coating adhesion will be discussed.

PMID- 15448414
TI  - Phase-contrast microtomography of thin biomaterials.
AB  - Phase-contrast microtomography, performed at the beamline ID 22 of the European
      Synchrotron Radiation Facility (ESRF, Grenoble, France), is demonstrated for high
      resolution 3-D imaging of a hydroxyapatite sample. The technique, which relies on
      phase contrast imaging, gives the possibility to observe features inside samples
      with negligible absorption contrast. The positive results obtained suggest a
      possible future investigation of the influence of the distribution of pores and
      defects inside biomaterial coatings, on the growth of osteoblast cells.

PMID- 15448415
TI  - Update on liver cell transplantation.

PMID- 15448416
TI  - Preparation and handling of powdered infant formula: a commentary by the ESPGHAN
      Committee on Nutrition.
AB  - Powdered infant formulae are not sterile and may contain pathogenic bacteria. In
      addition, milk products are excellent media for bacterial proliferation.
      Multiplication of Enterobacter sakazakii in prepared formula feeds can cause
      devastating sepsis, particularly in the first 2 months of life. In approximately
      50 published case reports of severe infection, there are high rates of
      meningitis, brain abscesses and necrotizing enterocolitis, with an overall
      mortality from 33% to 80%. Breast feeding provides effective protection against
      infection, one of the many reasons why it deserves continued promotion and
      support. To minimize the risk of infection in infants not fully breastfed,
      recommendations are made for preparation and handling of powdered formulae for
      children younger than 2 months of age. In the home setting, powdered infant
      formulae should be freshly prepared for each feed. Any milk remaining should be
      discarded rather than used in the following feed. Infant feeds should never be
      kept warm in bottle heaters or thermoses. In hospitals and other institutions
      written guidelines for preparation and handling of infant formulae should be
      established and their implementation monitored. If formula needs to be prepared
      in advance, it should be prepared on a daily basis and kept at 4 degrees C or
      below. Manufacturers of infant formulae should make every effort to minimize
      bacterial contamination of powdered products.

PMID- 15448417
TI  - Goat milk allerginicity.

PMID- 15448418
TI  - Resistant starch--an adjunct to oral rehydration solution: not yet ready for
      prime time.

PMID- 15448419
TI  - Growth failure and metabolic bone disease in progressive familial intrahepatic
      cholestasis.

PMID- 15448420
TI  - Serum transaminases in children with Wilson's disease.
AB  - OBJECTIVES: The response of serum transaminase levels to penicillamine and zinc
      treatment in Wilson's disease is poorly understood. The aim of this multicenter
      retrospective study was to evaluate transaminase levels after penicillamine and
      zinc treatment in children with Wilson's disease. PATIENTS AND METHODS: One
      hundred and nine patients with Wilson's disease (median age at diagnosis, 7.2
      years; range, 1 to 18 years), treated for at least 12 months and observed in the
      last 20 years at 11 Paediatric Departments were studied. Clinical, laboratory and
      histologic features at diagnosis and initial treatment were recorded. Efficacy
      parameters were normalization of serum transaminase level and improved clinical
      and/or laboratory signs. One hundred and two patients had clinical or laboratory
      signs of liver disease. RESULTS: Fifty-six of 87 patients (64%) given
      penicillamine normalized serum alanine aminotransferase (ALT) levels within a
      median of 17 months (range, 2 to 96 months). Of the 29 patients with persistent
      hyper-ALT, 17 (59%) switched to zinc; only four of these normalized ALT on zinc
      within a median period of 38 months (range, 7 to 48 months). Eleven (50%) of the
      22 patients given zinc alone normalized ALT within a median period of 6 months
      (range, 1 to 36 months). Of the 11 patients with persistent hyper-ALT, five
      switched to penicillamine. Three of the five normalized ALT within a median
      period of 6 months (range, 6 to 9 months). Overall, in penicillamine-treated and
      zinc-treated patients with persistent hypertransaminasemia, ALT decreased from a
      basal median of 236 IU/L (range, 54 to 640 IU/L) to a median of 78 (range, 46 to
      960 IU/L) at the end of follow-up (P = 0.0245). Poor compliance was suspected in
      only 10% of cases. No predictive factor of persistent hypertransaminasemia was
      identified. Liver disease did not worsen in any patient during the study.
      CONCLUSIONS: Although the efficacy of penicillamine and zinc is well documented,
      it is notable that a subset of children with Wilson's disease-related liver
      disease (36%) had hypertransaminasemia despite appropriate treatment with
      penicillamine or zinc.

PMID- 15448421
TI  - Immunogenicity and safety of an inactivated hepatitis A vaccine in children with
      Down syndrome.
AB  - OBJECTIVES: Hepatitis A vaccine has not been investigated in children with Down
      syndrome. The aim of this study was to evaluate immunogenicity and safety of an
      inactivated hepatitis A vaccine in noninstitutionalized children with Down
      syndrome and compare their responses to those of healthy control children.
      METHODS: An open, prospective, controlled trial of 127 children ages 1 to 12
      years, 63 with Down syndrome and 64 healthy control subjects, was conducted at a
      single hospital. Inactivated hepatitis A virus (HAV) vaccine containing 720
      enzyme-linked immunosorbent assay units of alum-adsorbed HAV was administered
      intramuscularly in a two-dose schedule at 0 and 6 months. Seroconversion and anti
      HAV titers were measured at months 1 and 7. RESULTS: Seroconversion rates at
      month 1 were 92% and 94% and geometric mean titers (GMT) were 164.02 and 160.77
      mIU/mL in the Down syndrome (DS) and control groups, respectively. At month 7,
      seroconversion rates were 100% in both groups, with GMT of 1,719.86 and 2,344.90
      mIU/mL in the DS and control groups, respectively (P = 0.117). Both doses were
      well tolerated and no significant adverse events observed. Local reaction at the
      injection site was the most common adverse event reported in both groups (15% in
      DS and 11% in controls). CONCLUSIONS: The authors' data demonstrate a good
      response to HAV vaccination in children with DS living at home, with GMT not
      statistically different from that of healthy control children. HAV vaccine is
      well tolerated and highly immunogenic in children with DS.

PMID- 15448422
TI  - Extraction of di-ethylhexyl-phthalate from perfusion lines of various material,
      length and brand by lipid emulsions.
AB  - BACKGROUND: The plasticizer di-ethylhexyl-phthalate (DEHP) is extracted
      especially by lipid emulsions from polyvinylchloride infusion systems. The aim of
      this study was to systematically examine the extraction from perfusion lines
      commonly used in our hospital for lipid emulsion infusions. METHODS: Perfusion
      lines made from polyvinylchloride of various lengths and brands, polyethylene,
      polyvinylchloride/polyethylene (PVC/PE) and polyvinylchloride/polyurethane
      (PVC/PU), were perfused with lipid emulsions according to the circumstances of
      newborns on an intensive care unit, i.e. high temperature, 24-hour duration and
      low quantities. Concentration of di-ethylhexyl-phthalate was determined with gas
      chromatograph mass spectrometry. RESULTS: The lipid emulsions before perfusion
      had a contamination with DEHP of 0.82 microg/ml. Pure PVC lines of 1.5 m length
      leached between 74 microg/ml and 107 microg/ml. Sterilization of the lines did
      not influence DEHP extraction. After perfusion of DEHP-free PVC lines and PVC
      free lines, the emulsions had a contamination with DEHP of 0.23 microg/ml and
      0.11 microg/ml, respectively. PVC/PU co-extruded lines leached 73 microg/ml.
      PVC/PE lines leached 41.6 microg/ml. CONCLUSIONS: Lipid emulsions contain a
      production-inherent load of DEHP. Perfusion through PVC-perfusion lines extracts
      a varying large amount of DEHP depending on length and brand of the perfusion
      lines. Co-extruded PVC/PU and PVC/PE lines, intended to avoid DEHP contamination,
      leach a similar amount of DEHP and thus do not avoid the DEHP toxicity issue. The
      load accumulated by a baby on an intensive care unit easily reaches several
      milligrams of DEHP per day. As its effect upon biologic systems has been proven,
      and alternatives (PE or PU perfusion lines) are available, PVC and PVC co
      extruded perfusion lines should be abandoned for infusions, especially in babies.

PMID- 15448423
TI  - Nutrition of very low birth weight infants fed human milk with or without
      supplemental trace elements: a randomized controlled trial.
AB  - BACKGROUND: Very low birth weight infants (<1500 g) have high nutritional needs.
      Deficiencies of minerals, trace elements (especially zinc) may develop as a
      result of rapid growth, low body stores and low content of these substances in
      human milk We hypothesized that fortification of human milk might prevent
      deficiencies. METHODS: Prospective, randomized trial to evaluate mineral, trace
      element, thyroid status and growth of infants fed human milk fortified with
      different amounts of calcium, phosphorus and protein, with (BMF) or without (FM
      85) trace elements. Sixty-two infants, 1000 to 1499 g birth weight, were
      randomized. Minerals and trace elements in serum, red blood cells and human milk
      and alkaline phosphatase activity, TSH, T4 and FT4 in serum were measured once
      until the fifth day and at 3 and 6 weeks of life. Clinical course and
      anthropometric measurements were recorded. RESULTS: Intake of zinc, copper,
      manganese, calcium, phosphorus and magnesium was higher in the BMF group (P <
      0.001). Serum zinc concentrations <0.49 mg/L occurred in 12% of the FM 85 group
      and 7% of the BMF group at 6 weeks (not significant). Median alkaline phosphatase
      activity was 436/379 IU/L in the FM 85/BMF group at 6 weeks (P < 0.01). The FM 85
      group showed a higher weight gain (P < 0.05), possibly because of higher caloric
      (P < 0.01) and protein intake (P < 0.05) at 3 weeks. CONCLUSIONS: Zinc deficiency
      was rare. Elevated intake of calcium, phosphorus and zinc was associated with
      lower serum alkaline phosphatase activity but did not influence serum zinc
      concentration.

PMID- 15448424
TI  - Goat milk is less immunogenic than cow milk in a murine model of atopy.
AB  - OBJECTIVES: Cow milk protein allergy occurs in 2% to 6% of infants population.
      Goat milk has been used as an alternative to cow milk, but there is probably some
      cross-reactivity between the milks. Little is known about the allergenicity of
      goat milk per se. The aim of this study is to compare cow and goat milk
      allergenicity in a mouse atopy model. METHODS: Balb/C mice were intragastrically
      sensitized to cow or goat milk by five doses administrated weekly. Six weeks
      after the first dose mice were killed, sera were collected and spleens removed
      for analysis. RESULTS: The number of mice with diarrhea was significantly higher
      in the cow milk-sensitized group than in the goat milk-sensitized group. Serum
      cow milk-specific immunoglobulin G1 and histamine levels were also significantly
      higher in cow milk-sensitized mice. Cytokine production by spleen derived T cells
      showed a Th2 response with high levels of interleukin-4 production and low levels
      of interferon-gamma in cow milk-sensitized mice. In addition, goat milk induced a
      lower lymphocyte sensitization as a result of a significant decrease in the
      specific proliferation ratio of these cells. CONCLUSION: Goat milk, when used as
      the first source of protein after a breast-feeding period, is less allergenic
      than cow milk in mice. Further studies are needed to clarify if goat milk is
      suitable as an alternative to cow milk in milk based formulas for infant
      nutrition.

PMID- 15448425
TI  - Adult-type hypolactasia: clinical, morphologic and functional characteristics in
      Brazilian patients at a university hospital.
AB  - BACKGROUND: Adult-type hypolactasia (AH) is the most common form of
      disaccharidase deficiency in humans, with a prevalence that varies among ethnic
      groups. In Brazil, the few available studies suggest a high prevalence of this
      condition. The objective of this study was to determine the prevalence of AH in
      Brazilian patients at the Ribeirao Preto University Hospital, and to study its
      morphologic and functional expression. METHODS: One hundred fifteen patients
      between 5 and 60 years undergoing upper gastrointestinal endoscopy were included.
      Mucosal biopsy specimens were obtained from the second portion of the duodenum.
      AH was defined by the disaccharidase activity (lactase/sucrase ratio) of the
      duodenal mucosa. The morphologic expression of lactase was studied by
      immunohistochemistry. RESULTS: The mean age of the subjects was 28.8 +/- 14.8
      years. Seventy of the 115 subjects (60.8% prevalence) had AH by enzyme activity
      measurements. Milk drinking was common and similar in patients with and without
      AH. Among the patients, 91.3% of the nonwhite and 53.2% of the white individuals
      had hypolactasia (P = 0.002). Immunohistochemistry revealed the presence of
      lactase in 73.3% of individuals with normal lactase activity. Two different
      expression patterns were found in patients with AH. CONCLUSIONS: The prevalence
      of AH was high in our subjects and similar to that reported in other Brazilian
      studies. Hypolactasia was more common among nonwhites. Immunohistochemistry
      permitted the identification of two phenotypes of AH, the first characterized by
      the absence of both stainable lactase and lactase activity, and the second by the
      presence of stainable lactase without significant activity.

PMID- 15448426
TI  - Variations in incidence of necrotizing enterocolitis in Canadian neonatal
      intensive care units.
AB  - OBJECTIVES: Necrotizing enterocolitis (NEC) is the most common acquired
      intestinal disease of neonates. Previous reports on incidence have generally
      examined small cohorts of extremely low-birth-weight infants and have not
      examined risk-adjusted variations among neonatal intensive care units (NICUs).
      The authors examined risk-adjusted variations in the incidence of NEC in a large
      group of Canadian NICUs and explored possible therapy-related risks. METHODS: The
      authors obtained data on 18,234 infants admitted to 17 tertiary level Canadian
      NICUs from January 1996 to October 1997. They used multivariate logistic
      regression analysis to examine the inter-NICU variation in incidence of NEC, with
      adjustment for population risk factors and admission illness severity, and
      explored therapy-related variables. RESULTS: The incidence of NEC was 6.6% (n =
      238) among 3,628 infants with birth weight < or = 1,500 g (VLBW), and 0.7% (n =
      98) among 14,606 infants with birth weight > 1,500 g (HBW). Multivariate logistic
      regression analysis showed that for VLBW infants, NEC was associated with lower
      gestational age and treatment for hypotension and patent ductus arteriosus. Among
      HBW infants, NEC was associated with lower gestational age, presence of
      congenital anomalies (cardiovascular, digestive, musculoskeletal, multiple
      systems) and need for assisted ventilation. There was no significant variation in
      the risk-adjusted incidence of NEC among NICUs, with the exception of one NICU
      reporting no cases of NEC. CONCLUSIONS: Risk factors for NEC were different in
      VLBW and HBW infants. There was no significant variation in the risk-adjusted
      incidence of NEC among Canadian NICUs, with one possible exception.

PMID- 15448427
TI  - Eosinophilic esophagitis in children: symptoms, histology and pH probe results.
AB  - AIM: To review the authors' experience with eosinophilic esophagitis. METHODS:
      Between 1993 and 2001, the authors identified 12 patients with eosinophilic
      esophagitis defined on histologic criteria (> or = 20 eosinophils per high-power
      field in the distal esophageal epithelium). The authors reviewed medical records
      for details of clinical presentation; laboratory data; radiologic, endoscopic,
      and histologic findings; and the results of continuous esophageal pH probe
      monitoring. RESULTS: Seventy-five percent of the patients were male. The median
      age at presentation was 10.8 years (range, 1-17 years). Commonly reported
      symptoms were dysphagia with solid food (66%), epigastric pain (42%), food
      impaction (50%), and vomiting (8%). Food allergy was reported in 50% and asthma
      in 33%. Peripheral eosinophilia (> 700/mm3) was found in 42%. Upper
      gastrointestinal series performed in eight patients, showed esophageal luminal
      narrowing in three. Computed tomography, performed in two patients, revealed
      thickening of the esophageal wall. Esophageal pH probe monitoring, performed in
      nine patients, revealed no abnormal acid reflux. All of the monitored patients
      had episodic alkalinization of the esophagus. Upper endoscopic analysis revealed
      white specks on the esophageal mucosa in 42%, esophageal narrowing in 33%,
      esophageal rings in 25%, and esophageal furrowing in 8%. The mean eosinophils per
      high-power field was 65 (range, 20-200). Histologic characteristics included
      juxtaluminar (33%) and peripapillary clusters of eosinophils (33%), increased
      papillary height (50%), and basal cell hyperplasia (34%). CONCLUSION: Solid food
      dysphagia was the most common feature of eosinophilic esophagitis in our
      patients. Alkalinization of the esophagus was found in all nine pH probe
      recordings of eosinophilic esophagitis patients and may represent a previously
      unreported characteristic of the condition.

PMID- 15448428
TI  - Gastric emptying and small intestinal transit time in preterm infants: a
      scintigraphic method.
AB  - OBJECTIVES: Practical methods to determine gastric emptying (GE) and small
      intestinal transit time in preterm infants are required. The aim of this study
      was to develop a scintigraphic method to determine GE and small intestinal
      transit time in preterm infants which produce minimal radiation exposure and
      physical disturbance in these infants. METHODS: Ten premature infants were
      studied. Median (and range) for gestational age was 28.9 (26-33) weeks, postnatal
      age was 19 (6-37) days, birth weight was 1194 (687-2300) grams and feeding volume
      was 173 (6-205) mL/kg/day. Nine of the patients were on nasal continuous positive
      airway pressure; one patient was on mechanical ventilation. A dose (0.2-0.4 MBq)
      of 99mTc-DTPA (0.5 mL) was given at the end of a meal administered by naso
      gastric tube. Static images were obtained with a mobile gamma camera during the
      next 9 to 12 hours. The radiation dose was at most 0.30 mSv. Regions of interest
      (ROIs) were drawn around the stomach and the cecum. Time-activity curves were
      generated. Gastric emptying half-time (T(1/2)GE) was calculated. Residual gastric
      activity after 1 hour (R(1h)) and after 2 hours (R(2h)) was determined. Orocecal
      transit time was defined as the time until significant increase in activity was
      detected in the cecal ROI. RESULTS: Images showed gastric emptying in all cases.
      Median (range) half time was 1.0 (0.5-3.0) h. R(1h) was 37.5% (19% to 100%),
      R(2h) was 23% (6% to 61%). In one patient the tracer did not reach the cecum
      within 12 hours. In the remaining nine patients orocecal transit time was 3.1
      (1.3-6.1) h. CONCLUSIONS: We present a new scintigraphic method to determine GE
      and orocecal transit time. It appears safe and practicable as a research tool in
      preterm infants.

PMID- 15448429
TI  - Severe gastroesophageal reflux disease and cow milk hypersensitivity in infants
      and children: disease association and evaluation of a new challenge procedure.
AB  - BACKGROUND: Gastroesophageal reflux disease (GERD) and cow milk hypersensitivity
      are frequent disorders of infancy. A possible causative association between these
      two entities has been suggested. OBJECTIVE: The primary aim was to elucidate
      whether a causative relationship between the two entities could be established in
      a population of infants and children. A secondary aim was to evaluate whether cow
      milk challenge during esophageal pH monitoring is useful as an objective method
      to identify this subgroup of patients. METHODS: Upper endoscopy followed by a 48
      hour esophageal pH monitoring with cow's milk elimination diet at day 1 and
      challenge at day 2. Cow milk hypersensitivity was later verified by elimination
      diet and a second open (in patients < 3 years of age) or double-blind placebo
      controlled (in patients > or = 3 years of age) challenge. Skin prick test,
      specific serum immunoglobulin E and skin patch test were used as supplementary
      procedures. Follow-up endoscopy and pH monitoring were performed after 3 months
      of treatment (omeprazole versus elimination diet dependent on evidence of food
      hypersensitivity). RESULTS: Eighteen of 42 investigated patients had severe GERD,
      defined as endoscopic esophagitis and/or a reflux index > 10%. Among these
      patients, a group of 10 patients with GERD and cow milk hypersensitivity was
      identified. This group had a significantly higher reflux index compared with
      children with primary GERD. No significant increase was noted in reflux index
      during simultaneous pH monitoring and milk challenge. CONCLUSIONS: An association
      between GERD and cow milk hypersensitivity was observed in both infants and
      children with severe GERD. Simultaneous cow milk challenge and pH monitoring had
      limited value as a method to identify this subgroup.

PMID- 15448430
TI  - Clinical usefulness of culturing H. pylori from gastric juice in patients with
      severe neurological impairment.
AB  - OBJECTIVES: To clarify the diagnostic usefulness of culturing Helicobacter pylori
      from gastric juice for the diagnosis of H. pylori infection in patients with
      neurologic impairment. METHODS: Seventy-five patients (44 males, 31 females) with
      severe neurologic impairment admitted to Tokyo Children's Rehabilitation Hospital
      were included in this study. Samples of gastric juice obtained from these
      patients were put into Helicoporter, a transport medium for H. pylori. Samples
      were then centrifuged and sediment was inoculated onto a culture medium.
      Polymerase chain reaction assays were performed on 41 gastric juice samples for
      comparison with results of culture. Tests for occult blood in gastric juice and
      serum anti-H. pylori immunoglobulin G were tested for all patients. RESULTS: H.
      pylori was isolated from 33 of 75 gastric juice samples by culture (positive
      rate, 44%). There was agreement between results of culture and polymerase chain
      reaction assays in 38 samples (93%). Twenty-two samples were positive and 16 were
      negative by both methods. In H. pylori immunoglobulin G-positive patients, occult
      blood was more frequently found in the culture-positive group (92%) than in the
      culture-negative group (59%) (P <0.025). The rate of detection of occult blood in
      immunoglobulin G-negative patients was similar in the culture-positive group
      (44%) and culture-negative group (50%). CONCLUSIONS: The combination of a culture
      method using gastric juice and a serum H. pylori immunoglobulin G assay was not
      invasive and clinically useful for evaluating H. pylori infections among
      handicapped patients.

PMID- 15448431
TI  - Depressive symptoms and inflammatory bowel disease in children and adolescents: a
      cross-sectional study.
AB  - OBJECTIVES: This study assessed the rates of depressive symptoms in older
      children and adolescents with inflammatory bowel disease (IBD) and the
      associations between depressive symptoms and IBD disease characteristics.
      METHODS: One hundred and two youths (aged 11-17 years) with IBD seen
      consecutively in a gastroenterology clinic were screened for depressive symptoms
      using the Children's Depression Inventory (CDI). Subjects with CDI scores > or =
      12 were evaluated for current psychiatric diagnoses using the Schedule for
      Affective Disorders and Schizophrenia for School-Age Children-Present and
      Lifetime Version (K-SADS-PL). Disease characteristics examined included IBD type,
      duration, current severity, course, age at diagnosis and steroid treatment.
      RESULTS: Of the total sample, 25 (24.5%) had a CDI score > or = 12, consistent
      with clinically significant depressive symptoms. Nineteen of 25 qualified
      subjects participated in the K-SADS-PL semi-structured interview and 16 of 19 met
      criteria for major or minor depressive disorder. Mean CDI scores positively
      correlated with age at IBD diagnosis but not with IBD type, duration or course.
      Youths with moderate/severe current IBD-related symptoms had significantly higher
      mean CDI scores than those with inactive disease activity. Anhedonia, fatigue and
      decreased appetite were selectively correlated with IBD disease severity.
      Subjects on steroids were more likely to have CDI scores > or = 12, and those
      with such scores were on higher doses of steroids than subjects without
      clinically significant depressive symptoms (both P values < 0.05). CONCLUSIONS:
      These findings support the recommendation that adolescents with IBD in outpatient
      medical care settings, particularly older adolescents and those on steroids,
      should be screened for depression.

PMID- 15448432
TI  - Resistance to parathyroid hormone in two patients with familial intrahepatic
      cholestasis: possible involvement of the ATP8B1 gene in calcium regulation via
      parathyroid hormone.

PMID- 15448433
TI  - Improved neurocognitive function after radiologic closure of congenital
      portosystemic shunts.

PMID- 15448434
TI  - Cytomegalovirus-associated hemophagocytic syndrome in a child with Crohn disease
      receiving azathioprine.

PMID- 15448435
TI  - Leukocytapheresis with leukocyte removal filter for severe ulcerative colitis in
      childhood.

PMID- 15448436
TI  - Vomiting and gastroparesis in thoracic myelopathy with pure sympathetic
      dysfunction.

PMID- 15448437
TI  - Peliosis hepatis in childhood: case report and review of the literature.

PMID- 15448438
TI  - Clinical quiz. Toxocara canis infection with hepatic and lung involvement.

PMID- 15448439
TI  - The frequency of CARD 15 mutations in the paediatric population.

PMID- 15448440
TI  - Two cases of Lactobacillus bacteremia during probiotic treatment of short gut
      syndrome.

PMID- 15448442
TI  - Safety and efficacy of octreotide in the immediate control of oesophageal
      variceal bleeding.

PMID- 15448444
TI  - Powerful new genetic tools may unlock old mysteries.

PMID- 15448445
TI  - The relationship of proximal locking screws to the axillary nerve during
      antegrade humeral nail insertion of four commercially available implants.
AB  - OBJECTIVE: The purpose of this study was to determine the proximity of proximal
      interlocking mechanisms in 4 current antegrade humeral nails to the axillary
      nerve and its branches. DESIGN: Cadaveric study. SETTING: Anatomy laboratory.
      MAIN OUTCOME MEASURE: Anatomic relationships. METHODS: Four humeral nail designs
      (labeled SS, SL, SZ, and SN) were each inserted in successive antegrade fashion
      in 10 cadaveric upper extremity specimens. Three variables were measured: from
      acromion to the axillary nerve, from acromion to entry sites of proximal locking
      devices, and from locking devices to axillary nerves and their branches. RESULTS:
      In nail SS, the proximally directed oblique locking screw came into contact with
      the ascending branch of the axillary nerve in 6 of 10 specimens. Mean distance
      from spiral blades in nails SS and SL were 26 mm to the axillary nerve and 16 mm
      to its ascending branch. Interlocking screws for nails SZ, SN, and SL did not
      violate the axillary nerve or its branches in any specimen. Mean distance from
      lateral acromion to the axillary nerve measured 58.7 mm. CONCLUSION: Nail SS's
      oblique locking screw may injure the ascending branch of the axillary nerve.
      Three of the 4 nails tested did not endanger the axillary nerve. However, when
      transverse proximal locking screws are inserted from a lateral-to-medial
      direction, they may endanger an arborized axillary nerve. Blunt dissection should
      be performed with a visible path to bone before instrumentation to reduce the
      risk of axillary nerve injury.

PMID- 15448446
TI  - Biomechanical comparison of sacroiliac screw techniques for unstable pelvic ring
      fractures.
AB  - OBJECTIVE: To determine the stiffness and strength of various sacroiliac screw
      fixations to compare different sacroiliac screw techniques. DESIGN: Randomized
      comparative study on embalmed human pelvises. MATERIALS AND METHODS: In 12
      specimens, we created a symphysiolysis and sacral fractures on both sides. Each
      of these 24 sacral fractures was fixed with 1 of the following methods: 1
      sacroiliac screw in the vertebral body of S1, 2 screws convergingly in S1, or 1
      screw in S1 and 1 in S2. On the left and right side of a pelvis, different
      techniques were used. The pubic symphysis was not stabilized. We measured the
      translation and rotation stiffness of the fixations and the load to failure using
      a 3-dimensional video system. RESULTS: The stiffness of the intact posterior
      pelvic ring was superior to any screw technique. Significant differences were
      found for the load to failure and rotation stiffness between the techniques with
      2 screws and a single screw in S1. The techniques utilizing 2 screws showed no
      differences. CONCLUSIONS: Based on the results of this study, we can conclude
      that a second sacroiliac screw in completely unstable pelvic fractures increases
      rotation stiffness and improves the load to failure.

PMID- 15448447
TI  - The efficacy of the A-V Impulse system in the treatment of posttraumatic swelling
      following ankle fracture: a prospective randomized controlled study.
AB  - OBJECTIVES: To determine whether the use of the A-V Impulse "in-cast" system
      conveyed any clinical benefit in the treatment of post-traumatic swelling
      following ankle fracture. DESIGN: A prospective randomised study comparing the
      effectiveness of the A-V Impulse "in-cast" system to that of elevation and
      plaster in the treatment of preoperative swelling. SETTING: Clinical management
      in a large level 2 trauma center. PATIENTS: Sixty-four adult patients were
      recruited to the study who had sustained closed unilateral ankle fractures
      requiring internal fixation, but for whom immediate surgery was not possible.
      INTERVENTION: All fractured ankles were treated with initial application of a
      plaster back-slab splint. Patients were randomized to either a control group of
      limb elevation or to a study group in whom an A-V Impulse bladder was fitted
      under the arch of the foot within the plaster back-slab and intermittent
      pneumatic pedal compression provided until surgery. MAIN OUTCOME MEASUREMENTS:
      Daily circumferential ankle girth measurements were performed. The time taken for
      swelling to resolve sufficiently to permit surgery, the development of skin
      complications, and the duration of hospitalisation were recorded. RESULTS: Ten
      patients were withdrawn from the study. Twenty-seven patients in each group were
      followed up until discharge from outpatient care. Statistical analysis revealed a
      significant reduction in time taken for ankle swelling to settle prior to surgery
      (P = 0.01) in the study group, together with a reduction in wound and skin
      complications (P < 0.01) and final preoperative ankle swelling (P = 0.03).
      CONCLUSION: The A-V Impulse "in-cast" system demonstrated significant benefit in
      the management of adults with isolated ankle fractures who could not undergo
      immediate open reduction and internal fixation.

PMID- 15448448
TI  - Point of view.

PMID- 15448449
TI  - Nonunions of the distal tibia treated by reamed intramedullary nailing.
AB  - OBJECTIVE: The purpose of this study is to determine the efficacy of reamed
      intramedullary nailing in the treatment of nonunions of the distal one-fourth of
      the tibia. Nonunions of the distal tibia are particularly difficult to treat
      given the short distal segment, the proximity to the ankle joint, and the fragile
      soft-tissue envelope. Intramedullary nailing is an attractive solution to this
      problem because it avoids extensive dissection, and the implant remains
      intraosseous, posing minimal problem for the soft tissues. DESIGN: Retrospective
      review of patient charts and radiographs. SETTING: Tertiary care orthopaedic
      hospital. PATIENTS/PARTICIPANTS: Thirty-two patients with nonunions of the distal
      one-fourth of the tibia. Prior treatments included casting, internal fixation
      with plates and screws, intramedullary nailing, and external fixation. Seven
      patients had a history of infection, but no patient had signs of active infection
      at the time of surgery. INTERVENTION: Study patients were treated by reamed,
      locked intra-medullary nailing. MAIN OUTCOME MEASUREMENTS: Main outcome
      measurements included time to union, correction of deformity, and complications
      including infection and reoperation. RESULTS: Average length of follow-up was 25
      months (range 4-81 months). Twenty-nine out of 32 patients achieved union at an
      average of 3.5 months after reamed, locked intramedullary nailing. Of the
      remaining three, 2 patients united after dynamization (one at 4 months after
      dynamization and the other at 7 months), and the third patient united 4 months
      after exchange nailing. Deformity was corrected to a maximum of 4 degrees in all
      planes. Four patients had positive intraoperative cultures, and only 2 required
      removal of the nail after achieving union to control infection. There were no
      signs of chronic osteomyelitis in these 2 patients at the date of the last follow
      up visit; 5.5 years and 2 years following nail removal. CONCLUSIONS: Reamed,
      locked intramedullary nailing is a reliable and safe procedure in the treatment
      of nonunions in the distal one-fourth of the tibia, even in the setting of prior
      infection or external fixation. It allows for excellent correction of deformity,
      which is an essential component of the procedure.

PMID- 15448450
TI  - Oblique screws at the plate ends increase the fixation strength in synthetic bone
      test medium.
AB  - OBJECTIVE: To test the hypothesis that oblique screws at the ends of a plate
      provide increased strength of fixation as compared to standard screw insertion.
      DESIGN: Biomechanical laboratory study in synthetic bone test medium. METHODS:
      Narrow 4.5-mm stainless steel low-contoured dynamic compression plates were
      anchored with cortical screws to blocks of polyurethane foam. The fixation
      strength in cantilever bending (gap closing mode) and torsion was quantified
      using a material testing system. Different constructs were tested to investigate
      the effect of the screw orientation at the end of the plate (straight versus
      oblique at 30 degrees), the plate, and bridging length as well as the number of
      screws. RESULTS: An oblique screw at the plate end produced an increased strength
      of fixation in all tests; however, the difference was more significant in shorter
      plates and in constructs with no screw omission adjacent to the fracture site.
      Both longer plates and increased bridging length produced a significantly
      stronger construct able to withstand higher compression loads. Under torsional
      loading, the fixation strength was mainly dependent on the number of screws.
      CONCLUSIONS: The current data suggest that when using a conventional plating
      technique, plate length is the most important factor in withstanding forces in
      cantilever bending. With regard to resisting torsional load, the number of screws
      is the most important factor. Furthermore, oblique screws at the ends of a plate
      increase fixation strength.

PMID- 15448451
TI  - Increased insertion torque delays pin-bone interface loosening in external
      fixation with tapered bone screws.
AB  - OBJECTIVE: To test the null hypothesis that osseomechanical integration is not
      related to the maximum insertion torque of tapered external fixation pins.
      DESIGN: Prospective in vivo study in a functionally loading ovine model. In 12
      animals, tapered commercial external fixation pins were inserted at predefined
      locations with measured insertion torques and extraction torque measured at 10
      weeks postoperatively. SETTING: Unrestricted stall activity under veterinary
      supervision. INTERVENTIONS: Under general anesthesia and aseptic conditions, mid
      diaphyseal tibial osteotomies were created and a 3-mm gap width stabilized with a
      custom-made, high-precision, single-sided external fixator, in compliance with
      United Kingdom government regulations [Animals (Scientific Procedures) Act 1986].
      MAIN OUTCOME MEASUREMENTS: Primary pin site stability and interface load were
      assessed by measuring maximum insertion torque (Nm). At a 10-week postoperative
      end point, osseomechanical stability was assessed by measuring the extraction
      torque and a pin performance index determined from the insertion/extraction
      torque ratio. RESULTS: A positive correlation was found between extraction torque
      and insertion torque (R2 = 0.322, P < 10(-6)). All pins with an insertion torque
      equal to or greater than 7 Nm had a measurable extraction torque, as did 98% of
      the pins with an insertion torque above 5 Nm. Extraction torque decreased both as
      a function of pin site position by the postoperative end point. High insertion
      torques were found to enhance end point stability in both diaphyseal and
      metaphyseal bone. CONCLUSION: The data from this study indicate that tapered
      external fixation pins should be inserted with a high torque to enhance the long
      term integrity of the pin-bone interface.

PMID- 15448452
TI  - The Levine anterior approach for total hip replacement as the treatment for an
      acute acetabular fracture.
AB  - The treatment of acetabular fractures in part relies on the selection of a
      specific surgical approach that allows for accurate reduction of fracture
      fragments. Moreover, these acetabular approaches were not developed for the
      insertion of a total hip replacement. Therefore, if a total hip arthroplasty is
      to be the treatment of an acute acetabular fracture, a single incision that
      permits reduction of the acetabular fracture fragments and ease of insertion of
      the arthroplasty components would be desirable. The Levine anterior approach
      provides both accesses to the anterior wall/column for reduction and fixation and
      to the femoral shaft for insertion of a total hip replacement. This paper
      describes that surgical technique and our initial clinical experience with this
      approach for acute acetabular fractures. A consecutive group of 10 patients with
      acetabular fractures, all involving the anterior wall/column with articular
      impaction (>50% of the acetabular roof) including 2 cases with an associated
      posterior hemitrans-verse component, were reviewed. After fracture reduction and
      fixation, a hybrid total hip replacement was implanted in all cases with an
      average acetabular component size of 56 mm (range 52-64). At a mean follow-up of
      36 months (range 24-53), all fractures united, and all acetabular components
      remained fixed with no evidence of migration or loosening. There were 2
      complications, a Brooker grade II heterotopic ossification and 1 postoperative
      anterior dislocation treated successfully with closed reduction and spica cast
      immobilization. The average Merle d'Aubigne hip score at latest follow-up was 16
      (range 13-18). The Levine anterior approach is a reliable, safe, and efficient
      technique that permits early mobilization of patients with anterior wall/column
      acetabular fractures requiring a total hip replacement.

PMID- 15448453
TI  - Entrapment of the external iliac vein in a both-column acetabular fracture.
AB  - We present a patient with an associated both-column acetabular fracture with
      entrapment of the external iliac vein in the fracture. This complication was not
      recognized until fracture manipulation during open reduction and fixation. This
      case report demonstrates that an acetabular fracture can have an associated
      vascular injury without any obvious clinical signs. This can be especially
      dangerous during percutaneous manipulation and fixation of these fractures as an
      obstruction or injury to the external iliac vein may occur and remain
      unrecognized. We feel that any surgeon involved in treating patients with
      acetabular or pelvic fractures should be aware of this potentially serious
      complication.

PMID- 15448454
TI  - Bilateral sacroiliac joint dislocation without associated fracture or anterior
      pelvic ring injuries.
AB  - SI joint dislocations are serious injuries. They are often associated with
      posterior fractures or anterior ring disruptions. This case report documents the
      outcome of a patient with an uncommon injury involving bilateral SI joint
      dislocation without associated anterior pelvic injuries or posterior pelvic
      fracture.

PMID- 15448455
TI  - Open subtalar dislocation treated by distractional external fixation.
AB  - Subtalar dislocation is a rare injury, constituting approximately 1% of acute
      dislocations, and often is the result of high-energy trauma, particularly falls
      from heights. We present a case of a 33-year-old man who sustained a Gustilo type
      IIIB open subtalar dislocation when he fell 4 m from a scaffold. After irrigation
      and debridement, a Mitkovic distractional external fixator was applied medially
      for 6 weeks while the wound healed by secondary intention. Physical therapy was
      initiated along with partial to full weight bearing during the next 3 months. The
      patient returned to work at 8 months postinjury. At 24 months, the patient had a
      normal gait with pain only during prolonged periods of standing or walking. X
      rays and MRI were normal with no signs of avascular necrosis or posttraumatic
      arthritis. Ankle joint range of motion was dorsiflexion 5 degrees and plantar
      flexion 45 degrees with moderately limited subtalar joint motion. The
      distractional external fixator allowed for complete wound care and unburdening of
      the talus, which perhaps reduced the possibility of avascular necrosis.

PMID- 15448456
TI  - Cervical teardrop fracture: Opinion: posterior fixation.

PMID- 15448457
TI  - Cervical teardrop fracture: Opinion: anterior fixation.

PMID- 15448458
TI  - On the shoulders of giants.

PMID- 15448459
TI  - Oral health research at the crossroads: translate we must!

PMID- 15448460
TI  - An evidence-based analysis of the antibacterial effectiveness of intracanal
      medicaments.
AB  - The authors reviewed the literature evaluating the antibacterial effectiveness of
      intracanal medicaments used in the management of apical periodontitis. A PICO
      (problem, intervention, comparison, outcome) strategy was developed to identify
      studies dealing with calcium hydroxide, phenolic derivatives, iodine-potassium
      iodide, chlorhexidine, and formocresol. The final inclusion/exclusion criteria
      eliminated all papers except five that evaluated calcium hydroxide. The total
      sample size in the included studies was 164 teeth. Microbiologic sampling was
      performed before endodontic treatment (S1), after instrumentation and irrigation
      (S2), and after intracanal medication (S3). At S2, 62% of canals were positive.
      After medication, 27% still showed detectable growth. Of cultures that were
      positive at S2, 45% were still positive at S3. Most studies did not address
      issues of culture reversals or false positive and false negative cultures. The
      main component of antibacterial action appears to be associated with
      instrumentation and irrigation, although canals cannot be reliably rendered
      bacteria free. Calcium hydroxide remains the best medicament available to reduce
      residual microbial flora further.

PMID- 15448461
TI  - Cold testing through full-coverage restorations.
AB  - Endodontic diagnosis often requires thermal testing through porcelain fused-to
      metal (PFM) and all-ceramic restorations. The purpose of this study was to
      measure and compare the temperature change during thermal testing by three
      commonly used methods occurring at the pulp-dentin junction (PDJ) of nonrestored
      teeth and teeth restored with full coverage restorations made of PFM, all
      porcelain, or gold. The methods used to produce a thermal change were (a) an ice
      stick, (b) 1,1,1,2-tetrafluoroethane (TFE), and (c) carbon dioxide snow. A
      thermocouple measured temperature changes occurring at the PDJ in 10 extracted
      premolars when thermal tested by each method over a period of 30 seconds.
      Temperature reduction was also measured for the same samples restored with full
      gold crowns, PFM, and Empress crowns. Results showed intact premolars and those
      restored with PFM or all-ceramic restorations to respond similarly to thermal
      testing. In these teeth, TFE produced a significantly greater temperature
      decrease than carbon dioxide snow between 10 and 25 seconds (p < 0.05). In
      conclusion, application of TFE on a saturated #2 cotton pellet was the most
      effective method for producing a temperature reduction at the PDJ of intact teeth
      and those restored with gold, PFM, and all-porcelain when testing for less than
      15 seconds.

PMID- 15448462
TI  - Effects of sonicated Enterococcus faecalis extracts on interleukin-2 and
      interleukin-4 production by human T cells.
AB  - In the present authors' previous study, sonicated Enterococcus faecalis extracts
      were shown to suppress the cell cycle progression of human lymphocytes. To study
      the effect of this microorganism on the function of lymphocytes, the authors
      investigated the levels of interleukin-2 (IL-2) and interleukin-4 (IL-4)
      production by T lymphocytes before and after the addition of sonicated E.
      faecalis extracts. In this study, levels of IL-2 and IL-4 produced from T cells
      were evaluated by using the quantitative sandwich enzyme immunoassay technique.
      In response to phytohemagglutinin (PHA) stimulation, T cells produced increased
      levels of IL-2 and IL-4. However, the expressions of both cytokines were
      significantly inhibited when PHA-activated T cells were preexposed to 12.5
      microg/ml and 25 microg/ml of sonicated E. faecalis extracts (p < 0.05). This
      effect was concentration-dependent, because the levels of IL-2 and IL-4
      expressions were not affected by the addition of a low concentration (5
      microg/ml) of sonicated extract. These findings suggest that Th1 and Th2
      immunosuppression mediated by E. faecalis could be a part of the pathogenic
      mechanism of the endodontic failure associated with this microorganism.

PMID- 15448463
TI  - Induction of vascular endothelial growth factor gene expression by
      proinflammatory cytokines in human pulp and gingival fibroblasts.
AB  - Vascular endothelial growth factor (VEGF) enhances the permeability of blood
      vessels, which is an important vascular change observed during inflammatory
      processes. The purpose of this in vitro study was to investigate the effect of
      proinflammatory cytokines on the expression of VEGF mRNA gene in human pulp and
      gingival fibroblasts. Interlukin-1alpha (IL-1alpha) and tumor necrosis factor
      alpha (TNF-alpha) were used to evaluate VEGF mRNA gene expression in human pulp
      and gingival fibroblasts. The levels of mRNAs were measured by quantitative
      reverse-transcriptase polymerase chain reaction analysis. Both IL-1alpha and TNF
      alpha induced significantly high levels of VEGF mRNA gene expression in human
      pulp and gingival fibroblasts (p < 0.05). In addition, TNF-alpha was found to be
      more effective in the induction of VEGF mRNA gene expression in pulp than
      gingival fibroblasts (p < 0.05). Moreover, IL-1alpha was found to be more
      effective in the induction of VEGF mRNA gene expression than TNF-alpha in
      gingival fibroblast cultures (p < 0.05). These results indicate that
      proinflammatory cytokines can induce VEGF mRNA gene expression, and such an
      effect may partially contribute to the destruction of pulpal and periapical
      tissues through promoting expansion of the vascular network coincident to
      progression of the inflammation.

PMID- 15448464
TI  - In vivo study on the biocompatibility of newly developed calcium phosphate-based
      root canal sealers.
AB  - This study compared the biocompatibility of two new calcium phosphate-based root
      canal sealers (CAPSEAL I, CAPSEAL II) with another type of commercially available
      calcium phosphate sealer (Apatite Root Sealer type I, Apatite Root Sealer type
      II) and a zinc oxide eugenol-based sealer (Pulp Canal Sealer EWT) after
      implanting them in the subcutaneous tissue of rats. After 1, 2, 4, and 12 weeks,
      the tubes were removed with the surrounding tissues. The tissue reactions were
      graded as being mild or 1, moderate or 2, and severe or 3 after a
      histopathological examination. The results were analyzed statistically with the
      Kruskal-Wallis test. The biocompatibility of the materials was interpreted
      according to the Federation Dentaire Internationale criteria (1980). The
      inflammatory reactions decreased with time. The new sealers showed a lower tissue
      response than any of the other sealers in all the experimental periods. All the
      tested sealers showed an acceptable biocompatibility.

PMID- 15448465
TI  - Identification of resected root-end dentinal cracks: a comparative study of
      transillumination and dyes.
AB  - The dilemma of diagnosing and possibly treating dentinal cracks continues to
      present a challenge in endodontics. The purpose of this in vitro study was to
      compare the effectiveness of transillumination and dyes in identifying root-end
      dentinal cracks. Fifty maxillary central incisors were decoronated, and the
      canals were instrumented to an ISO size 50 at the working length. The apical 3 mm
      of the roots was resected, and cracks were artificially created in the apical
      dentin. Four independent examiners evaluated the root ends at x8 magnification
      with a surgical operating microscope using transillumination (group 1), sodium
      fluorescein dye (group 2), caries detect dye (group 3), methylene blue dye (group
      4), and methylene blue plus transillumination (group 5). The examiners' ability
      to identify root ends correctly with and without cracks was analyzed by comparing
      the data with the predetermined standard (cracked and noncracked) using logistic
      regression analysis. All techniques used were shown to be more effective than
      random chance at diagnosing cracks. The areas under the curve of the different
      techniques were as follows: transillumination, 0.81 (95% confidence interval
      [CI], 0.69-0.93); sodium fluorescein, 0.72 (95% CI, 0.58-0.86); caries detector,
      0.76 (95% CI, 0.63-0.89); methylene blue, 0.70 (95% CI, 0.55-0.84); and methylene
      blue plus transillumination, 0.82 (95% CI, 0.70-0.94). Thus, the crack assessment
      techniques that gave the best discrimination between cracked and noncracked
      specimens, regardless of rater, was methylene blue plus transillumination. This
      study emphasizes the usefulness of transillumination along with magnification in
      detecting dentinal cracks.

PMID- 15448466
TI  - Effect of pitch length on the behavior of rotary triple helix root canal
      instruments.
AB  - The behavior of nickel-titanium instruments depends largely on the cross-section
      of the working part. The effect of pitch length was evaluated using two
      instruments with the same cross-section (triple helix; 0.6% taper). One had a
      short pitch (0.5 mm at the tip to 0.9 mm at 16 mm at the end of the working
      part). The other had a long pitch (1.18 mm/2 mm). A dynamometer recorded
      tensional stress (MHz) and the tendency to screw in (Fz) during simulated canal
      preparations. Rotational speed was kept constant, and a continuous pecking
      movement was used. At the end of the preparations, the average Fz was 5.02 N for
      the short-pitch instrument and 1.47 N for the long-pitch instrument (p < 0.001).
      The average Mz varied from 0.88 N (short pitch) to 0.35 N (long pitch).
      Increasing the pitch decreased torsional load sharing and the tendency to screw
      in.

PMID- 15448467
TI  - Three-step versus single-step use of system B: evaluation of gutta-percha root
      canal fillings and their adaptation to the canal walls.
AB  - This study aimed to evaluate the quality of gutta-percha (GP) root canal fillings
      and their adaptation to the root canal walls, when the System B was used in three
      steps and a single step to fill three different split-tooth models. Each model
      was filled 10 times in two different ways. Group A: the System B plugger was used
      to fill the apical 3 mm of the canal in three steps, and then the Obtura II was
      used to backfill the rest of the canal. Group B: the System B plugger was
      inserted just once to a distance 3 mm short of the working length and then
      backfilled as in Group A. Replication of artificial depressions, presence of
      voids within the GP mass, and presence of spaces between the GP mass and the root
      canal walls were evaluated and scored. The individual scores of each parameter
      evaluated were compared between the two groups and statistically analyzed by use
      of the Mann-Whitney U test. Group A showed statistically significant (p < 0.05)
      better scores than Group B concerning the replication of artificial depressions
      and spaces between the GP mass and the canal walls. It was concluded that better
      adaptation of the GP mass to the canal walls in the apical third was obtained
      when the System B plugger was used in three steps.

PMID- 15448468
TI  - Factors influencing defects of rotary nickel-titanium endodontic instruments
      after clinical use.
AB  - This study examined used, discarded rotary nickel-titanium instruments obtained
      from 14 endodontists in four countries, and identified factors that may influence
      defects produced during clinical use. A total of 7,159 instruments were examined
      for the presence of defects. Unwinding occurred in 12% of instruments and
      fractures in 5% (1.5% torsional, 3.5% flexural). The defect rates varied
      significantly among endodontists. Instrument design factors also influenced
      defect rate, but to a lesser extent. The mean number of uses of instruments with
      and without defects was 3.3 +/- 1.8 (range: 1-10), and 4.5 +/- 2.0 (range: 1-16),
      respectively. The most important influence on defect rates was the operator,
      which may be related to clinical skill or a conscious decision to use instruments
      a specified number of times or until defects were evident.

PMID- 15448469
TI  - Clinical management of a maxillary lateral incisor with vital pulp and type 3
      dens invaginatus: a case report.
AB  - A maxillary right lateral incisor with a type 3 dens invaginatus and a large
      periapical lesion with vital pulp in a separate root canal was treated both
      nonsurgically and surgically. Care was taken not to expose or devitalize the
      vital pulp in the main root canal system during the treatment. The signs and
      symptoms ceased after the treatment, and 4-month recall showed complete bone
      healing with pulp vitality maintained.

PMID- 15448472
TI  - Proceedings of the 9th Annual Meeting of the Kyoto Cornea Club. Kyoto, Japan,
      December 5-6, 2003.

PMID- 15448470
TI  - Management of arsenic trioxide necrosis in the maxilla.
AB  - Historically, pulp-necrotizing agents were commonly used in endodontic
      treatments. They act quickly and devitalize the pulp within a few days. However,
      they are cytotoxic to gingiva and bone. If such an agent diffuses out of the
      cavity, it can readily cause widespread necrosis of gingiva and bone, which can
      lead to osteomyelitis of the jaws. Although the use of arsenic trioxide can cause
      severe damage to surrounding tissues, producing complications, it is still used
      in certain areas in the world. This article presents and discusses two cases of
      tissue necrosis and their surgical management. These cases showed severe alveolar
      bone loss in the maxilla, which affected the patients' quality of life and
      limited the restorative possibilities. As dentists, we should be aware of the
      hazardous effects of arsenic trioxide and should abandon its use. Because of its
      cytotoxicity, there is no justification for the use of arsenic trioxide in the
      modern dental practice.

PMID- 15448473
TI  - Isolation and clonal characterization of hematopoietic and liver stem cells.
AB  - PURPOSE: Prospective isolation of stem cells is essential to understanding the
      mechanisms that control their proliferation and differentiation. METHODS AND
      RESULTS: Using 9 monoclonal antibodies and fluorescence-activated cell sorting
      (FACS), we have succeeded in prospectively identifying hematopoietic stem cells
      (HSCs) in adult mouse bone marrow. Mouse HSCs were exclusively enriched in CD34
      negative, c-Kit Sca-1 Lineage Marker (CD34 KSL) cells representing 0.004% of bone
      marrow (BM) mononuclear cells. When single CD34-KSL cells were transplanted
      individually into a lethally irradiated mouse, 25% of the recipient mice survived
      and showed long-term reconstitution of the BM, providing evidence for
      multipotency and a self-renewal capacity of HSCs. Using a similar approach, we
      also prospectively identified hepatic stem cells with multilineage
      differentiation potential and self-renewal capability in the c-Met CD49f c-Kit
      CD45 Ter119 fraction of cells isolated from day 13.5 fetal mouse liver. On cell
      transplantation, these cells differentiated into hepatocytes and cholangiocytes.
      As an alternative to the antibody based stem cell isolation, Hoechst33342
      staining is useful. To understand the mechanism responsible for SP phenotype, we
      performed an expression cloning and identified bcrp-1/ABCG2 gene, a member of ATP
      binding-cassette (ABC) transporter family. Bcrp-1 is almost exclusively expressed
      in CD34 KSL cells among blood cells; however their expression in other tissue
      specific stem cells remains to be studied. CONCLUSION: With the use of FACS and
      monoclonal antibodies, hematopoietic and liver stem cells were prospectively
      isolated and characterized. HSCs could also be purified by Hoechst 33342
      staining. By expression cloning, we identify bcrp-1/ABCG2 transporter as a
      molecule responsible for SP phenotype. Elucidation of the physiological role of
      bcrp-1/ABCG2 in HSCs may provide us with clues to understand the molecular
      mechanisms of stem cell self-renewal and differentiation.

PMID- 15448474
TI  - Human corneal endothelial cell proliferation: potential for use in regenerative
      medicine.
AB  - PURPOSE: To review and update the experience of our laboratory in culturing human
      corneal endothelial cells (HCEC) from young and older donors. METHODS: Corneas
      were obtained from National Disease Research Interchange, Philadelphia, PA. Data
      from the past 3 years were reviewed to develop criteria for selecting donor
      corneas to be used for endothelial cell culture. Immunocytochemical localization
      using mAb 9.3.E identified endothelial cells, and Ki67 staining demonstrated
      actively cycling cells. Cell counts demonstrated the effect of growth-promoting
      agents on proliferation of cells from young (<30 years old) and older (>50 years
      old) donors. Phase-contrast microscopy documented morphologic characteristics of
      cells in primary culture and the effect of growth factors on cell morphology.
      RESULTS: Exclusion criteria were developed to increase the chance of successful
      culture of HCEC. Isolation methods to remove Descemet membrane with attached
      endothelial cells avoided contamination with other corneal cell types. EDTA
      treatment combined with mechanical disruption facilitated isolation of cells.
      Culture medium containing FBS, EGF, NGF, and bovine pituitary extract stimulated
      maximal growth and facilitated normal monolayer formation. Age-related
      differences were detected in the density of confluent cells in primary culture
      and in the proliferative response to growth-promoting agents. CONCLUSIONS:
      Untransformed HCEC can be successfully cultured from the corneas of both young
      and older donors by using care in the selection of donor material. Care must also
      be taken in the early phases of endothelial cell isolation to obtain maximal
      numbers of healthy cells for culture. There appear to be true age-related
      differences in overall proliferative capacity; however, the relative response to
      specific growth factors was similar in cells from young and older donors. Results
      of these studies provide guidelines for successful growth of untransformed HCEC
      for use in regenerative medicine.

PMID- 15448475
TI  - Quantification of tear interference image: tear fluid surface nanotechnology.
AB  - PURPOSE: To review the literature on lipid supplementation therapy for dry eye
      and on image analysis using tear interference images from the specific tear lipid
      layer interference camera DR-1. METHODS: Systematic literature review of lipid
      supplementation therapy for lipid tear deficiency dry eye, kinetic analysis of
      tear interference images using DR-1 camera, and computer-synthesized interference
      color chart for DR-1 camera. CONCLUSION: To establish lipid supplementation
      therapy, a quantification system of tear lipid layer is required. Tear lipid
      thickness could be quantified using a computer-synthesized interference color
      chart system.

PMID- 15448476
TI  - TGF-beta signal transduction in corneal wound healing as a therapeutic target.
AB  - This article reviews recent progress in research on the role of Smad signaling in
      corneal wound healing. Smad2 and Smad3 are key signaling molecules downstream of
      the cell surface receptor of transforming growth factor-beta (TGF-beta) or
      activin. On ligand binding to the receptor, Smads2/3 undergo phosphorylation,
      form complexes with Smad4, and thence convey signaling. TGF-beta isoforms have
      been detected in corneal epithelium and are also deposited in wounded stroma,
      suggesting their participation in the wound-healing process in corneal tissue.
      Human or mouse uninjured healthy corneal epithelium shows nuclear accumulation of
      Smads3/4, indicating active Smad signaling in this tissue. Migrating corneal
      epithelium lacks nuclear Smad accumulation with up-regulation of Smad7, but
      p38MAPK is activated. Organ-culture experiments show that p38MAPK activation
      depends on endogenous TGF-beta and that activation of p38MAPK results in cell
      proliferation cessation with a reduction of Erk activation and acceleration of
      cell migration in healing corneal epithelium. These findings indicate that during
      healing of corneal epithelial defects, endogenous TGF-beta activates p38MAPK for
      cell migration and suppression of cell proliferation and up-regulates Smad7 for
      inhibition of Smad2 and Smad3 signaling, resulting in rapid initial resurfacing
      of the epithelium. Such involvement of p38MAPK in cell migration has been
      reported in many cell types and observed in keratocyte culture. Possible benefits
      of preserving non-Smad cascades in treating problems in corneal wound healing by
      manipulating TGF-beta signals have been suggested.

PMID- 15448477
TI  - Component surgery of the cornea.
AB  - Penetrating keratoplasty (PKP) has long been the standard procedure for treating
      irreversible opacification of the cornea from various diseases. The success rate
      of PKP is high compared with those in other organ transplants because of the low
      incidence of immunologic rejection. However, once rejection does occur, secondary
      procedures are inevitably less successful. Cases with vascularized corneas are
      also prone to undergo rejection, and severe disease causing total destruction of
      limbal tissue is considered a contraindication for surgery. Recent advances in
      corneal surgery aim at reducing surgical trauma to the host cornea by replacing
      only necessary cells and tissue. This approach not only reduces the risk of
      immunologic rejection but may also yield better refractive results. The various
      transplantable "components" of the cornea include the epithelium, epithelial stem
      cells, stroma, and endothelium. Cells from these components can be transplanted
      as lamellar sections of donor cornea or as sheets using biologic carriers and
      scaffolds. Procedures such as epithelial sheet transplants using amniotic
      membrane carriers, deep lamellar keratoplasty, and endothelial lamellar
      keratoplasty are already in clinical practice. Further refinements in technology
      will certainly take the limits of corneal surgery to new horizons.

PMID- 15448478
TI  - Potential use of (1,3)-beta-D-glucan as target of diagnosis and treatment of
      keratomycosis.
AB  - PURPOSE: Major problems in the management of keratomycosis stem from the
      difficulty of its diagnosis and limited choice of antifungal agents. In the
      present paper we propose a new method of detecting (1,3)-beta-D-glucan, one of
      the major components of fungal cell wall, in tears from an animal model of
      keratomycosis. In addition, we investigated the efficacy of topical application
      of micafungin, a new antifungal agent that inhibits the activity of (1,3)-beta-D
      glucan synthase in this animal model. METHOD: Candida albicans (5 x 10(5)
      organisms) was inoculated into the corneal stroma of 20 New Zealand White
      rabbits. The animals were randomly assigned to two groups and treated with
      subconjunctival injection of 0.5 mL of saline or 0.1% micafungin every day for 3
      weeks. The clinical course of keratomycosis in both groups was compared. Before
      and 3 weeks after the injection of saline or micafungin, 5 microL of tears in
      each eye were collected by capillary tube. The concentration of (1,3)-beta-D
      glucan was quantitatively measured by modified Limulus test. RESULTS: The
      concentration of (1,3)-beta-D-glucan was significantly higher in keratomycosis
      model animals than in controls (mean +/- SD, 17.4 +/- 9.4 pg/mL and 2.8 +/- 1.8
      pg/mL, respectively) at 21 days after treatment. Subconjunctival injection of
      micafungin had no significant effect on ocular lesions of keratomycosis until 9
      days, after which ocular lesions significantly improved. Subconjunctival
      application of micafungin decreased the concentration of (1,3)-beta-D-glucan in
      tears to 4.9 +/- 3.0 pg/mL at 21 days after treatment. CONCLUSIONS: Increased
      levels of (1,3)-beta-D-glucan in tears were detected in this model of
      keratomycosis. Measuring the concentration of (1,3)-beta-D-glucan in tears may be
      a reliable noninvasive method for the diagnosis of keratomycosis. Topical
      application of micafungin was effective in the treatment of keratomycosis.

PMID- 15448479
TI  - Microarray analysis in the HSV-1 latently infected mouse trigeminal ganglion.
AB  - PURPOSE: To review our previous studies regarding alterations in gene expression
      in HSV-1 latently infected mouse trigeminal ganglia (TGs) following treatment
      with immunosuppressants and hyperthermia. METHODS: Uninfected and HSV-1 latently
      infected mice were treated with immunosuppressants or heat stressed (43 degrees C
      for 10 minutes). In the immunosuppressant study, 4 groups of animals were
      examined: (1) uninfected, not treated; (2) uninfected, drug-treated; (3) latently
      infected, not treated; and (4) latently infected, drug-treated. In the
      hyperthermia study, TG from 6 groups of mice were studied: (1) uninfected, not
      stressed; (2) uninfected, heat-stressed; killed at 6 hours after hyperthermia;
      (3) uninfected, heat-stressed, killed at 24 hours after hyperthermia; (4)
      latently infected, not stressed; (5) latently infected, heat-stressed, killed at
      6 hours after hyperthermia; and (6) latently infected, heat-stressed, killed at
      24 hours after hyperthermia. PolyA mRNA from the TGs of each group was reverse
      transcribed, labeled with P, incubated on a gene array membrane, and analyzed by
      phosphorimaging. As a comparison and to confirm microarray results,
      semiquantitative RT-PCR for selected genes was also performed. RESULTS: The
      immunosuppressive drugs significantly increased expression of two genes-
      calpactin 1 light chain and guanine nucleotide-binding protein alpha stimulating
      activity polypeptide (GNAS)--in the ganglia of uninfected mice compared with
      untreated, uninfected mice. Ten genes were shown to be significantly increased in
      the latent TGs from mice treated with the immunosuppressants compared with
      latently infected untreated mice. These genes were prostaglandin E2 receptor EP4
      subtype (PTGER4), insulin promoter factor 1 (IPF1), glutathione S-transferase
      mu2, cyclin D2, peripherin, plasma glutathione peroxidase, methyl CpG-binding
      protein 2, retinal S-antigen, ErbB2 protooncogene, and GNAS. Eight genes were
      shown to be significantly decreased in the HSV-1 latent TGs treated with the
      drugs compared with untreated latent mice. These genes were peripheral myelin
      protein 22, decorin, transcription factor AP-1, dystroglycan 1, myelin protein
      zero, mitogen-activated protein kinase 3, prothymosin beta4, and brain lipid
      binding protein. The results obtained by semiquantitative RT-PCR results were
      similar to those obtained by microarray analysis. Six hours after heat stress,
      the genes whose expression was altered included the FK506-binding protein gene
      (decreased), the T-complex protein 1alpha subunit gene (increased), and the 94
      kDa glucose-regulated protein gene (increased in uninfected TG, decreased in
      infected TG). Heat stress increased expression of the DNA excision repair protein
      ERCC5 gene 24 hours after the treatment. Genes previously reported to exhibit
      increased transcription 1 hour after heat stress did not continue to show
      significant transcriptional activation at 6 or 24 hours. CONCLUSIONS: Those genes
      whose expression is altered by immunosuppressive drug treatment may play an
      important role in ocular HSV-1 recurrence. Changes in gene expression in the
      prostaglandin pathway, a transcription factor, and an enzyme in the cell cycle
      are considered of special importance for HSV-1 reactivation by immunosuppression.
      Altered gene expression at 6 and 24 hours after heat stress was different from
      previously reported changes in gene expression 1 hour after hyperthermia in HSV-1
      latently infected mice.

PMID- 15448480
TI  - Roles of chemokines in ocular allergy and possible therapeutic strategies.
AB  - The mechanism of ocular surface allergy in the forms of atopic conjunctivitis and
      vernal keratoconjunctivitis has been highlighted by specific functions of
      chemokines. In the context of late-phase allergic responses, these molecules have
      key roles in recruitment and activation of leukocytes. Their interaction with
      ligands is redundantly regulated; however, results from strategies to block
      subsets of chemokines have revealed unexpected or highly organized roles of these
      mediators. Exemplified by analyses of CCL11 function, current concepts of ocular
      allergy support CCL11 as central mediator. We emphasize the functions as
      modulator of mast cell activation/differentiation. With the prospect of
      understanding these functions, new modalities of drugs specifically developed to
      target CCL11/CCR3 interaction have been discussed.

PMID- 15448481
TI  - Corneal endothelial transplantation: results of a clinical series using deep
      lamellar endothelial keratoplasty (DLEK).
AB  - PURPOSE: We present the results of our clinical series replacing posterior stroma
      and endothelium only by deep lamellar endothelial keratoplasty (DLEK) in patients
      with corneal endothelial diseases. METHODS: Through a 9.0-mm superior scleral
      incision, a deep stromal pocket was created across the cornea. A 7.5-mm posterior
      lamellar disc of recipient tissue was excised and replaced by same-size donor
      posterior disc without suture fixation. Three cases were followed for 12 months
      after DLEK. Best spectacle-corrected visual acuity (BSCVA), endothelial cell
      density, and corneal thickness were examined. RESULTS: At 12 months after
      surgery, all transplants were clear and in position. In the 3 cases, BSCVA at 12
      months was 20/200 (hand motion before operation), 20/50 (6/200 before operation),
      and 20/60 (20/250 before operation), respectively. In one patient, postoperative
      endothelial cell density was 533 cells/mm(2) with a very thin donor disc. In the
      other two patients, postoperative endothelial cell density was >2000 cells/mm(2).
      Corneal thickness (+/-SD) averaged 0.51 +/- 0.06 mm. CONCLUSIONS: DLEK in the
      setting of corneal endothelial diseases is an effective surgical procedure
      without corneal surface incisions and sutures.

PMID- 15448482
TI  - Structural analysis of the cornea using scanning-slit corneal topography in eyes
      undergoing excimer laser refractive surgery.
AB  - PURPOSE: To review the time course of corneal anteroposterior shift and
      refractive stability after myopic excimer laser keratorefractive surgery.
      METHODS: We examined 65 eyes undergoing photorefractive keratectomy (PRK) and 45
      eyes undergoing laser in situ keratomileusis (LASIK). Corneal elevation maps and
      pachymetry were obtained by scanning-slit corneal topography before; 1 week; and
      1, 3, 6, and 12 months after surgery. RESULTS: Both PRK and LASIK induced
      significant forward shifts of the cornea. Corneal forward shift was progressive
      up to 6 months after PRK, but no progression was seen after LASIK. Progressive
      thinning and expansion of the cornea were not observed after either procedure.
      The amount of corneal forward shift showed a significant negative correlation
      with preoperative corneal thickness (r = -0.586; P < 0.01) and a significant
      positive correlation with the amount of myopic correction (r = 0.504; P < 0.01).
      A significant correlation was found between the amount of forward shift and the
      degree of myopic regression after surgery (r = -0.347; P < 0.05). CONCLUSION:
      Myopic PRK and LASIK induce significant forward shifts of the cornea, which are
      not true corneal ectasia. Eyes with thinner corneas and higher myopia requiring
      greater ablation are more predisposed to anterior protrusion of the cornea.
      Corneal forward shift was progressive up to 6 months after PRK but not
      progressive after LASIK. Forward shift of the cornea can be one of the factors
      responsible for myopic regression after surgery.

PMID- 15448483
TI  - Tear film stability analysis system: introducing a new application for
      videokeratography.
AB  - PURPOSE: To review our previous studies regarding the development of a tear
      stability analysis system (TSAS) using videokeratography and the clinical
      application of TSAS for evaluation of tear film stability in patients subject to
      laser in situ keratomileusis (LASIK). METHODS: New software, namely TSAS, was
      developed for the videokeratography system TMS-2N (topographic modeling system).
      TSAS automatically captures consecutive corneal surface images every second for
      10 seconds. Corneal topographs were analyzed for tear breakup time (TMS-BUT) and
      tear breakup area (TMS-BUA, the ratio of breakup area to entire color-code area).
      First, we recruited volunteers to test the sensitivity and specificity of this
      new system in comparison with the routine method for tear stability analysis,
      tear film breakup time evaluation by slit-lamp microscope (SLE-BUT), with
      fluorescence staining. Second, we investigated the practicability of TSAS in
      dynamic evaluation of tear film stability before and after LASIK. RESULTS: TMS
      BUT had a positive correlation with SLE-BUT, whereas TMS-BUA showed a negative
      correlation. Although they showed similar rates of specificity as SLE-BUT, the
      sensitivity rates of TMS-BUT and TMS-BUA were 97.5% and 95%, respectively,
      significantly higher than that of SLE-BUT (75%). The study on patients subject to
      LASIK showed that tear film stability significantly decreased during the early
      time period following LASIK and resolved at 6 months after surgery. Eyes that had
      abnormal TSAS evaluation tended to have higher risk of developing superficial
      punctuate keratitis and dry eye symptoms after LASIK, and their responses to
      treatment were slow. CONCLUSIONS: TSAS is a noninvasive and objective method with
      higher sensitivity for tear film stability analysis than SLE-BUT.

PMID- 15448484
TI  - Quantitative assessment of videokeratography data using fourier series harmonic
      analysis.
AB  - PURPOSE: To describe a method of mathematically decomposing videokeratography
      data using Fourier series harmonic analysis and present examples of its clinical
      application. METHODS: Videokeratography data were decomposed by Fourier analysis
      into spherical component, regular astigmatism, asymmetry (decentration or
      skewness), and higher-order irregular astigmatism. These 4 Fourier components
      were analyzed in both normal and pathologic eyes. Color-coded maps were generated
      to present the 4 Fourier components. RESULTS: Color-coded mapping of the results
      of Fourier analysis of videokeratography data facilitated visual and instant
      interpretation of complex corneal topographic information. By using Fourier
      components, time course of changes in corneal topography following penetrating
      keratoplasty and influence of suture removal were quantitatively evaluated. The
      Fourier analysis method was successfully applied to determine the most
      appropriate correction lenses in eyes after penetrating keratoplasty.
      CONCLUSIONS: Fourier analysis of videokeratography data allows mathematical
      separation of regular and irregular astigmatism and is useful in the quantitative
      assessment of corneal optics in eyes with both pathologic and postsurgical
      conditions.

PMID- 15448485
TI  - Corneal iron ring formation associated with overnight orthokeratology.
AB  - PURPOSE: To describe a case of iron deposition in both eyes after overnight
      orthokeratology. METHODS: This is a case report of a 31-year-old man who
      underwent overnight orthokeratology. The subject was fitted with rigid gas
      permeable contact lenses of reverse-geometry design to correct myopia. RESULTS:
      The prefitting manifest refraction was -4.75 -0.25 x 175 in the right eye and 
      4.50 -0.25 x 175 in the left eye. There was no corneal abnormality until 9 months
      after treatment, but development of corneal arcuate lines in both eyes was
      observed at the 1-year follow-up visit. Visual acuity was not affected. The
      deposition pattern corresponded to the outside border of central flatter zone, as
      shown on the corneal topography map. CONCLUSION: The current findings suggest
      that tear pooling between the corneal surface and the back surface of the contact
      lens plays a role in the development of corneal iron ring after orthokeratology
      with reverse-geometry contact lenses.

PMID- 15448486
TI  - Influence of overnight orthokeratology on corneal endothelium.
AB  - PURPOSE: To evaluate the influence of overnight orthokeratology on the corneal
      endothelium. METHODS: Fifty-two eyes of 31 patients undergoing overnight
      orthokeratology for myopia were examined. They wore the lens every night and were
      followed up for at least 1 year. The corneal endothelium was examined with
      specular microscopy to calculate mean endothelial cell density, coefficient of
      variation of cell area, and percentage of hexagonal cells. Data obtained at 1
      year follow-up examinations were compared with those at the baseline examinations
      using a paired t test. RESULTS: Orthokeratology significantly reduced manifest
      refraction from -2.32 +/- 1.18 D (mean +/- standard deviation) to -0.16 +/- 0.33
      D (P < 0.0001) and improved uncorrected visual acuity from 0.77 +/- 0.29 to -0.07
      +/- 0.10 logMAR (P < 0.0001). The endothelial cell density did not change
      significantly (2879 +/- 231 cells/mm before and 2864 +/- 260 cells/mm after
      treatment, P = 0.252). The coefficient of variation of cell area was 22.3 +/- 2.7
      at baseline and 22.1 +/- 2.4 at 1-year posttreatment, which did not change
      significantly (P = 0.537). The percentage of hexagonal cells was 72.8 +/- 10.2%
      pretreatment and 72.5 +/- 10.9% posttreatment (P = 0.800). CONCLUSIONS: Overnight
      orthokeratology for 1 year did not influence the density or morphology of corneal
      endothelial cells.

PMID- 15448487
TI  - Long-term changes in rabbit cornea after ionizing radiation.
AB  - PURPOSE: To investigate long-term changes in the cornea after ionizing
      irradiation in rabbits. METHODS: Mature albino rabbits (n = 4) were unilaterally
      irradiated with 20 Gy of x-rays. The contralateral eye served as a control. The
      rabbits were examined with slit-lamp biomicroscopy for 5 years. The eyes were
      then enucleated for histopathologic examinations with light microscopy and
      transmission electron microscopy. RESULTS: On biomicroscopy, there was no corneal
      abnormality during the 5-year follow-up period. On histopathology, no abnormality
      was observed in the corneal epithelium. In the endothelium, a vacuole-like
      structure was recognized by light microscopy, and transmission electron
      microscopy revealed marked enlargement of intercellular space and anamorphosis of
      the nuclei. CONCLUSION: Moderate x-ray irradiation to rabbit eye did not induce
      any long-term damage to the corneal epithelium, but the endothelium demonstrated
      persistent and irreversible damage, which was observed even 5 years after
      irradiation.

PMID- 15448488
TI  - The prevalence and risk factors for donor corneal button contamination and its
      association with ocular infection after transplantation.
AB  - BACKGROUND: One of the most serious complications of corneal transplantation is
      postoperative ocular infection, which may result in loss of the eye.
      Contamination of the donor corneal button before transplantation may result in
      such complication. PURPOSE: To evaluate the prevalence of donor corneal button
      contamination, the spectrum of the contaminating microorganisms, and their
      sensitivity to antimicrobial agents. To investigate the risk factors for
      contamination of the donor corneal buttons and the effect of corneal button
      contamination on the prevalence of ocular infection in corneal transplanted
      patients. SETTING: Tertiary referral medical center. MATERIALS AND METHODS: Four
      hundred sixty-nine corneal transplantations were included in the study. Microbial
      cultures from the corneoscleral rims of the donor corneal buttons were obtained
      for isolation of bacteria and fungi and for their sensitivity to antimicrobial
      agents. Ocular microbial cultures were also obtained from corneal transplanted
      patients with clinical signs of ocular infection (ie, corneal scrapes from
      corneal ulcers and vitreous tap from eyes with endophthalmitis). RESULTS: Seventy
      nine donor corneal buttons (16.8%) had positive bacterial cultures, and none had
      positive fungal culture. Staphylococci (63.7%) and streptococci (11.3%) were the
      most common isolated bacteria. Sensitivity to vancomycin, amikacin, and
      gentamicin was found in 71.3%, 28.5%, and 22.3% of all isolated bacteria,
      respectively. Malignancy and cardiac diseases as causes of donor death were
      associated with donor button contamination (P = 0.043 and P = 0.011,
      respectively), and septicemia was a marginally significant risk factor (P =
      0.059). Age and gender of the donor, duration from death to corneal button
      harvesting, and time from harvesting to transplantation were not found
      significant risk factors for contamination. Six of the corneal transplanted
      patients (1.27%) had infected corneal graft ulcer, and 1 (0.22%) had
      endophthalmitis. The infected corneal ulcer appeared between 3 and 14 days
      (average 5 days), and endophthalmitis was disclosed 8 months after
      transplantation. Two (33%) of the 6 patients with corneal ulcer had the same
      species as the donor corneal rim. Postoperative ocular infection occurred in 2
      (2.5%) patients out of 79 who received contaminated corneal buttons compared with
      5 (1.3%) out of 390 patients who received sterile corneal buttons (P = 0.335).
      CONCLUSIONS: Postkeratoplasty infection of the recipient eye is infrequent
      despite relatively high prevalence of microbial contamination of the corneal
      buttons, suggesting that other risk factors for postoperative ocular infection
      are involved.

PMID- 15448489
TI  - Keratoconus staging: a computer-assisted ultrabiomicroscopic method compared with
      videokeratographic analysis.
AB  - PURPOSE: The aim of this study was to introduce a new paradigm for keratoconus
      assessment, the keratoconus index (KI), generated from the ratio of peripheral
      corneal thickness (PCT) to the thinnest corneal thickness (TCT), and calculated
      by a computer-assisted procedure after ultrabiomicroscope (UBM) examination. Then
      we compared KI and the keratoconus severity index (KSI), obtained by
      videokeratography in patients with different stages of keratoconus. METHODS: We
      studied 60 eyes with different forms of keratoconus using the TMS-3
      autotopographer, provided with a keratoconus screening program (using Smolek
      Klyce methods) and the commercial version of the ultrasound biomicroscope
      (Paradigm UBM Plus Model P45) equipped with a 50-MHz probe, which was provided
      with our computer-assisted program. The proportion test Z and the correlation
      coefficient R were applied to the outcomes. RESULTS: The keratoconus severity
      index, KSI, obtained by color-coded videokeratographic maps, was in the range 95%
      to 32% (mean 52.22%). By means of UBM examination, we obtained 60 images and
      found values of TCT 0.278-0.592 mm and PCT 0.475-0.704 mm. Applying the computer
      assisted method, we obtained values for KI of 1.112-2.159 (mean 1.428).
      CONCLUSIONS: KI is correlated as well as KSI with the severity of the keratoconus
      (R = 0.76, P < 0.0001). It can be used as a similar parameter to measure the
      evolution of the disease, on the basis of corneal thickness rather than the
      curvature.

PMID- 15448490
TI  - Treatment of presbyopia with conductive keratoplasty: six-month results of the 1
      year United States FDA clinical trial.
AB  - PURPOSE: To provide 6-month results of a 1-year clinical trial evaluating
      conductive keratoplasty (CK) for the treatment of presbyopic symptoms in
      emmetropic and hyperopic eyes. METHODS: A total of 143 patients with presbyopic
      symptoms were enrolled in this 1-year United States FDA clinical trial and
      treated to improve near vision in 1 eye (unilateral treatment). In addition, 33
      fellow eyes were treated to improve distance vision (bilateral treatment). For
      near vision correction, the target refraction was up to -2.0 D in the nondominant
      eye, and for distance vision correction, 0.0 D. Enrolled patients had a
      preoperative spherical equivalent of plano to +2.00 D, no more than 0.75 D of
      refractive astigmatism, and were 40 years of age or older. No retreatments were
      performed. RESULTS: Of the eyes treated for near, 77% had uncorrected near vision
      of J3 or better at 6 months postoperatively. A total of 85% of all patients had
      binocular distance UCVA of 20/25 or better along with J3 or better near, a
      combination that represents functional acuity for a presbyope. Sixty-six percent
      of eyes treated for near had a manifest refractive spherical equivalent (MRSE)
      within +/- 0.50 D of intended at 6 months. In 89% of eyes, the MRSE changed 0.05
      D or less between 3 and 6 months postoperatively. After month 1, the incidence of
      variables associated with safety was 1% or lower. Seventy-six percent were very
      satisfied or satisfied with their procedure. CONCLUSIONS: CK appears to be very
      safe and effective in producing functional visual acuity in presbyopic eyes up to
      6 months following the procedure. Patient satisfaction with the procedure is
      similar to that of monovision LASIK.

PMID- 15448491
TI  - Anatomic study of the corneal thickness of young emmetropic subjects.
AB  - PURPOSE: To study the corneal thickness of young emmetropic subjects. METHODS:
      One thousand eyes of 1000 young healthy emmetropic subjects were analyzed with
      the Orbscan Topography System II (Orbscan, Inc, Salt Lake City, UT) from January
      2001 to May 2003. The age of the subjects ranged from 20 to 30 years old (mean +/
      SD = 27.12 +/- 2.86). The mean of 5 consecutive measurements of the corneal
      thickness in the center of the cornea and at temporal, superotemporal,
      inferotemporal, nasal, inferonasal, and superonasal cornea were recorded.
      RESULTS: The corneal thickness at the following areas ranged as follows: 518 to
      589 microm center; 603 to 678 microm nasal; 620 to 689 microm superonasal; 600 to
      669 microm inferonasal; 571 to 639 microm temporal; 601 to 669 microm
      superotemporal; and 572 to 647 microm inferotemporal. In each individual the
      difference between the central thickness and the maximum paracentral thickness
      ranged from 85 to 107 microm (mean +/- SD, 99.21 +/- 3.80). The difference
      between the central thickness and the minimum paracentral thickness ranged from
      36 to 59 microm (48.97 +/- 4.23 microm). The difference between the minimum
      paracentral corneal thickness and the maximum paracentral corneal thickness
      ranged from 37 to 58 microm (50.24 +/- 4.30). The tonometry was statistically
      correlated with the corneal thickness (P < 0.05 at each corneal location
      analyzed). CONCLUSIONS: In emmetropic corneas the difference between the minimum
      paracentral thickness and the maximum paracentral thickness was similar to the
      difference between the central thickness and the minimum paracentral thickness.

PMID- 15448492
TI  - Goldmann tonometry after hyperopic laser in situ keratomileusis: comparison
      between retreated and nonretreated patients.
AB  - PURPOSE: To identify differences in applanation tonometry between retreated and
      nonretreated eyes (primary LASIK eyes) 6 months after hyperopic laser in situ
      keratomileusis. METHODS: In a prospective study 100 eyes (100 patients) underwent
      conventional hyperopic laser in situ keratomileusis under a 160-microm flap.
      Central Goldmann applanation tonometry was determined before and 6 months after
      surgery in 78 (78%) primary LASIK eyes and before surgery and 6 months after the
      retreatment date in 22 (22%) retreated eyes. RESULTS: Preoperative mean tonometry
      was 14.96 +/- 1.96 mm Hg and 15.30 +/- 1.95 mm Hg in primary LASIK and retreated
      eyes, respectively. Six months after surgery it was 12.99 +/- 2.03 mm Hg (P <
      0.001) and 12.67 +/- 2.20 mm Hg (P < 0.001), respectively. No significant
      differences in mean tonometry were found between retreated and primary LASIK eyes
      6 months after surgery (P = 0.537). Decreased tonometric values were found in 20
      retreated eyes (90.91%) and in 62 primary LASIK eyes (79.48%). Increased
      tonometric values higher than 1 mm Hg were found in 3 primary LASIK eyes (3.84%),
      but no retreated eyes showed increased values 6 months after surgery. Two
      retreated eyes (9.09%) and 10 primary LASIK eyes (79.49%) presented the same
      tonometric values before surgery and at the end of the study. CONCLUSIONS: After
      hyperopic laser in situ keratomileusis there was no significant difference in
      Goldmann applanation tonometry between retreated and primary LASIK eyes.

PMID- 15448493
TI  - The epidemiology of diffuse lamellar keratitis.
AB  - PURPOSE: To report the incidence and outcomes of diffuse lamellar keratitis (DLK)
      after LASIK and to analyze potential causative factors. METHODS: Retrospective
      review of 15,119 cases (11,232 primary procedures and 3887 enhancements) from
      7168 patients undergoing LASIK from May 1995 through October 2002, comparing
      preoperative data and postoperative outcomes for each case developing DLK to
      patients in the study population and a control series of eyes that did not
      develop DLK. RESULTS: We identified 61 eyes (0.40%) that developed DLK after
      LASIK. Three study groups were identified based on sterilization protocols used:
      (1) steam autoclave without reservoir (8348 cases), (2) cassette autoclave with
      reservoir (6771 cases), (3) steam autoclave without reservoir and new instrument
      cleaner (1758 cases). Significantly more eyes developed DLK with Protocol 2 (47
      cases, 0.94%) than with Protocol 1 (11 cases; 0.1%; P < 0.0001) or Protocol 3 (3
      cases, 0.2%; P < 0.0005). There was no significant difference in the incidence of
      DLK in Protocol 1 versus Protocol 3. DLK was significantly more common after
      primary procedures than with enhancement procedures only under Protocol 2. No
      individual developed DLK after more than 1 procedure. Treatment protocols
      included frequent topical steroids only (24 cases, 39.3%), frequent topical
      steroids and oral steroids (19 cases, 31.2%), or topical and oral steroids
      combined with lifting and irrigating beneath the flap (18 cases, 29.5%). Final
      refractions and visual acuities were not significantly different in eyes that
      developed DLK and those that did not. CONCLUSIONS: DLK is a nonspecific
      inflammatory response to multiple stimuli that cannot be attributed solely to
      individual variation in the inflammatory response, the microkeratome, or material
      deposited by the microkeratome. Sterilizers with reservoirs may cause some cases
      of DLK. With appropriate diagnosis and treatment, DLK should resolve without
      sequelae, yielding visual outcomes comparable to cases with uneventful
      postoperative courses.

PMID- 15448494
TI  - Evaluation of normal corneas using the scanning-slit topography/pachymetry
      system.
AB  - PURPOSE: To obtain anterior and posterior corneal shape, curvature, and thickness
      of normal human corneas. To provide a semiquantitative analysis of normal
      topography patterns of the anterior and posterior corneal surfaces. METHODS:
      Eighty-eight healthy corneas of 44 normal subjects were analyzed using the
      scanning-slit topography/pachymetry system. Anterior and posterior elevation and
      mean power (central and steepest spherical and cylindrical) values and pachymetry
      data were determined. Right eye values were submitted for primary analysis;
      however, a comparison between right and left eyes was made in addition to test
      the possible reliability of the system. RESULTS: There was no significant
      difference between right and left corneas in 28 evaluated parameters, except for
      anterior central cylindrical (P = 0.005) and steepest cylindrical (P = 0.017)
      mean power. The anterior central spherical mean power correlated inversely with
      the posterior central spherical mean power (r = -0.27, P = 0.04), and the
      anterior steepest spherical mean power value showed inverse correlation with the
      mean posterior steepest spherical value (r = -0.44, P = 0.001). The mean central
      thickness of the cornea was 593.7 +/- 54.19 microm at the center and was 578 +/-
      50.53 microm at the thinnest point, which was localized in 41% (n = 18) of the
      cases in the inferotemporal quadrant. An oval-shaped pattern was the most
      characteristic feature of the anterior and posterior elevation, mean power, and
      pachymetry maps. CONCLUSION: Orbscan scanning-slit topography seems to be a
      reliable technique for the evaluation of normal corneas not only for anterior
      shape and curvature but also for a real pachymetry gradient recording.

PMID- 15448495
TI  - In vivo confocal microscopy: increased conjunctival or episcleral leukocyte
      adhesion in patients who wear contact lenses with lower oxygen permeability (Dk)
      values.
AB  - PURPOSE: Contact lens wear is known to threaten the health of the ocular surface.
      In vivo confocal microscopy (IVCM) to visualize leukocyte rolling and
      extravasation in inflammation was recently described. We tested the hypothesis
      that contact lens wear is associated with measurable inflammation in superficial
      vessels. METHODS: Leukocyte rolling and sticking (hallmarks of the inflammatory
      process) were recorded by IVCM. IVCM was performed on conjunctival or episcleral
      blood vessels bilaterally on 55 contact lens wearers (15 male, 40 female) and 22
      non-contact lens wearers (8 male, 14 female). Data were analyzed in 2 ways.
      Considering each vessel as an independent variable resulted in 132 analyzable
      vessel segments (13 daily disposable contact lenses, 67 traditional contact
      lenses, 14 rigid gas-permeable lenses, and 38 controls). Considering each subject
      as an independent variable resulted in analyzable data for 47 subjects (5 daily
      disposable contact lens wearers, 22 traditional contact lens wearers, 5 rigid
      contact lens wearers, and 15 control patients). Free-flowing, sticking, and
      rolling cells were counted in the vessels. Multiple parameters including mean
      flow velocity, shear rate, rolling cells/mm/min, and sticking cells/mm were
      calculated. RESULTS: We found no significant difference in leukocyte adhesion
      between control patients and patients wearing daily disposable, traditional
      disposable, or rigid gas-permeable lenses in both types of statistical analyses.
      However, the data regarding vessel segments as an independent variable show that
      there were more rolling cells in patients who wore contact lenses with oxygen
      permeability values (Dk) less than 10 as compared to those who wore contact
      lenses with oxygen permeability values greater than 16 (P < 0.01) or compared to
      controls (P < 0.01). CONCLUSION: IVCM is a novel, powerful technique to recognize
      a critical but subclinical component of inflammation. Although our data indicate
      that contact lens wear does not markedly increase rolling and sticking of
      leukocytes in conjunctival or episcleral vessels, there may be subclinical
      inflammation in association with lenses with the lowest oxygen permeability.

PMID- 15448496
TI  - Pachymetry of donor corneas: effect of ethnicity and gender on central corneal
      thickness.
AB  - PURPOSE: To examine demographic differences associated with the central corneal
      thickness (CCT) of donor corneas and to investigate whether these differences
      confirmed previous clinical studies. METHODS: CCT was prospectively measured
      using noncontact pachymetry among 704 eye bank corneas. The effects of gender,
      ethnicity, age, cause of death, times until preservation and evaluation, and
      endothelial cell density and morphometry on CCT were examined. RESULTS: The CCT
      of black women was significantly thinner (P = 0.05) than that of other corneal
      donors. The average CCT +/- SD of black women was 530 +/- 35.9 microm, whereas
      those of white and Hispanic women were 554 +/- 59.1 microm and 556 +/- 51.2
      microm, respectively. Average values for black, white, and Hispanic men were 553
      +/- 44.7 microm, 551 +/- 53.4 microm, and 543 +/- 50.4 microm, respectively. Age
      and cause of death did not significantly affect CCT. CONCLUSION: Gender may
      modify racial differences of CCT. Measurements using donated corneal tissues
      support pachymetric differences by ethnic origin, although this finding was
      limited to female donors only.

PMID- 15448497
TI  - Risk factors for corneal regraft in patients on the French waiting list.
AB  - PURPOSE: To determine the frequency of corneal regraft (CR) and to identify risk
      factors associated with CR for all primary diagnoses, secondary endothelial
      failure (SEF), and keratoconus. METHODS: This survey included 8904 eyes
      registered on the French national waiting list that underwent keratoplasty
      between 2000 and 2002. RESULTS: The frequency of CR was 14.0% for all diagnoses,
      16.9% among SEF patients, and 8.3% among keratoconus patients. For all diagnoses,
      the following factors were found to be independently associated with a
      significantly increased risk of CR (P < 0.05): primary diagnosis (stromal
      dystrophy, herpes simplex keratitis, SEF, trauma, and keratoconus with Fuchs
      dystrophy as reference), vascularization in more than 2 quadrants, planned
      recipient diameter over 8.5 mm, immunologic disorders, previous lens surgery
      (aphakic, pseudophakic anterior or posterior chamber intraocular lens), previous
      surgery for glaucoma or trauma, being grafted in 2001 or in 2002. For SEF
      patients, the risk factors were younger age, vascularization in more than 2
      quadrants, planned recipient diameter over 8.5 mm, immunologic disorders,
      previous surgery for glaucoma or trauma, associated cataract or dry eye, and
      graft year. For keratoconus patients, the risk factors for CR were older age,
      vascularization in more than 2 quadrants, immunologic disorders, and previous
      lens surgery. CONCLUSION: The frequency of CR increased in France over the 2000
      2002 time period. Patients presenting the above risk factors should be followed
      up closely to limit the loss of the first graft.

PMID- 15448498
TI  - Topical anesthesia for penetrating keratoplasty.
AB  - PURPOSE: To evaluate the use of topical anesthesia for penetrating keratoplasty
      (PKP) in situations where retrobulbar, peri/parabulbar, or general anesthesia are
      inadvisable or not readily available. METHODS: This was a retrospective analysis
      of a consecutive case series consisting of 8 eyes in 8 patients who had PKP with
      topical anesthesia between September 1995 and December 1997 in cases where
      retrobulbar, peri/parabulbar, or general anesthesia either could not be performed
      or presented too great a risk to the patient. Some cases were supplemented with
      small limbal injections, mild intravenous sedation (fentanyl), and/or intraocular
      anesthesia. In one case, intraocular 1% lidocaine was placed directly into the
      vitreous cavity to allow an open-sky vitrectomy. RESULTS: In all cases, PKP was
      completed without complications. All patients tolerated the procedure well and
      reported only mild discomfort. However, in 2 cases, an ACIOL was left in place
      because lens manipulation caused pain in the ciliary body and iris root areas.
      CONCLUSIONS: PKP can be performed successfully with topical anesthesia in
      cooperative patients who have perforated corneal ulcers, significant
      anticoagulation, or severe medical conditions, which make alternative forms of
      anesthesia more risky.

PMID- 15448499
TI  - Viability of porcine corneal epithelium ex vivo and effect of exposure to air: a
      pilot study for a dry eye model.
AB  - PURPOSE: To explore the use of an ex vivo, in situ porcine cornea as a model for
      dry eye (exposure keratitis). METHODS: Twenty-seven porcine eyes were obtained
      from freshly killed animals at the local abattoir. The viability of 9 corneas
      (control-baseline group) was assessed within 5 minutes after enucleation on site.
      A further 18 eyes were transported to the laboratory, where they were exposed to
      ambient conditions for 4 hours (experimental group A, 6 eyes), for 6 hours
      (experimental group B, 6 eyes), and for 4 hours with wetting with Dulbecco
      Phosphate-Buffered Saline every 5 minutes (exposure control group, 6 eyes). All
      corneas were assessed by trypan blue exclusion for cell viability. RESULTS: The
      number of dead cells in the central region was significantly greater than those
      in the peripheral region (P < 0.05) in all groups. The number of dead cells in
      both corneal areas increased significantly (P < 0.05) in the experimental groups
      with time of exposure, but there was no significant increase in the exposure
      control group. CONCLUSION: Preliminary data on the number of dead cells in
      porcine corneal epithelium after enucleation and the effect of exposure were
      obtained. It was found that after exposure to air, the corneal cells were
      maintained well by regular wetting, but there was progressively greater cell
      damage with exposure without wetting. These baseline data will be useful for the
      further development of the porcine dry eye model to investigate exposure
      keratitis.

PMID- 15448500
TI  - Corneal endothelial cell damage after lens extraction using the fluid-based
      system compared to ultrasound phacoemulsification in human cadaver eyes.
AB  - PURPOSE: To compare the endothelial cell damage after lens removal using a fluid
      based system to conventional ultrasound. METHODS: Twenty human cadaver eyes were
      randomized to undergo phacoemulsification using either a fluid-based system or
      conventional ultrasound. After surgery, each corneoscleral button was removed,
      stained and damaged endothelial cells per square millimeter were assessed using
      light microscopy. RESULTS: Fluid-based system mean damaged endothelial cells/mm
      was 60.2 +/- 24.1 compared with 60.4 +/- 42.6 when using conventional ultrasound
      (P = 0.248). CONCLUSION: The fluid-based system is as safe for the corneal
      endothelium as conventional ultrasound during cataract removal in human cadaver
      eyes.

PMID- 15448501
TI  - Dramatic healing of an allergic corneal ulcer persistent for 6 months by amniotic
      membrane patching in a patient with atopic keratoconjunctivitis: a case report.
AB  - PURPOSE: To present a case of allergic corneal ulcer in a patient with atopic
      keratoconjunctivitis (AKC) that was persistent for 6 months and healed by
      amniotic membrane patching. CASE REPORT: A 27-year-old male patient with a
      corneal ulcer associated with AKC persistent for 6 months despite conventional
      treatment underwent amniotic membrane patching. On removal of the amniotic
      membrane patch after 1 week, the corneal ulcer that had been persistent for 6
      months had healed completely. CONCLUSION: We experienced a case with corneal
      ulcer that was persistent for 6 months and healed dramatically within 1 week with
      improved vision and corneal clarity. In such severe and persistent cases
      requiring rapid epithelialization, amniotic membrane should be considered as an
      adjunct to conventional therapy.

PMID- 15448502
TI  - Adjunctive treatment with interferon alpha-2b may decrease the risk of papilloma
      associated conjunctival intraepithelial neoplasm recurrence.
AB  - PURPOSE: To report a case of bilateral papilloma virus-positive conjunctival
      intraepithelial neoplasm and the treatment results of using adjunctive interferon
      alpha-2b. METHODS: Case report and literature review. RESULTS: A 73-year-old man
      underwent subtotal excisional biopsy of the 270-degree gelatinous limbal lesion
      of the right eye to avoid creating a limbal deficiency and cicatricial change.
      Total excisional biopsy of the temporal elevated leukoplakic limbal lesion was
      performed on his left eye. Histology examination showed bilateral intraepithelial
      neoplasia, and human papilloma virus-16 and -18 were detected by polymerase chain
      reaction in both lesions. Two supplemental perilesional injections of interferon
      alpha-2b in the right eye were given, and the residual mass decreased in size
      gradually and completed clinical resolution 7 weeks following initial surgery.
      Although no recurrence was noticed in the right eye, recurrence of the
      conjunctival intraepithelial neoplasm lesion was noticed in the left eye.
      CONCLUSION: Adjunctive therapy might lower CIN recurrence rate, especially in
      extensive lesions, when surgical excision cannot ensure a tumor-free margin. Our
      bilateral case provided a good control example for the recurrence with or without
      adjunctive therapy.

PMID- 15448503
TI  - Scleral ulceration caused by Cryptococcus albidus in a patient with acquired
      immune deficiency syndrome.
AB  - PURPOSE: To describe a case of a scleral ulceration caused by Cryptococcus
      albidus in a patient with acquired immune deficiency syndrome (AIDS). DESIGN:
      Interventional case report. A 16-year-old girl with AIDS was admitted to the
      hospital with a 1-week history of cough, fever, and sudden onset of a painless
      scleral lesion on her left eye. Culture of the lesion revealed the fungus
      Crypotococcus albidus. RESULTS: The patient was treated with topical amphotericin
      B and systemic itraconazole, and she recovered fully over 4 weeks without
      sequelae. CONCLUSION: Cryptococcus albidus rarely causes disease in humans. It
      should be considered as a potential cause of ocular and systemic disease in
      patients with AIDS.

PMID- 15448504
TI  - Prevention of recurrent Reis-Bucklers dystrophy following excimer laser
      phototherapeutic keratectomy with topical mitomycin C.
AB  - PURPOSE: To report a case of excimer laser phototherapeutic keratectomy (PTK) for
      Reis-Bucklers dystrophy with a single intraoperative application of adjunctive
      topical 0.02% mitomycin C (MMC). METHODS: Interventional case report and review
      of the literature. RESULTS: A 73-year-old woman with visually significant Reis
      Bucklers dystrophy underwent PTK of her right eye with 0.02% adjunctive MMC for
      visual rehabilitation. Before treatment, best corrected visual acuity (BCVA) was
      20/400. The left eye had previously undergone PTK on 2 occasions without MMC, and
      the dystrophy had recurred following each treatment. One year after the
      procedure, her MMC-treated cornea remains clear with no recurrence of Reis
      Bucklers dystrophy. CONCLUSIONS: The use of topical MMC in conjunction with PTK
      may be a safe and effective treatment of Reis-Bucklers dystrophy and may be
      helpful in preventing recurrence of the disease.

PMID- 15448505
TI  - A case of rofecoxib-associated stevens-johnson syndrome with corneal and
      conjunctival changes.
AB  - PURPOSE: To report a case of rofecoxib (Vioxx)-associated Stevens-Johnson
      syndrome with corneal and conjunctival changes. DESIGN: Interventional case
      report. METHODS: Case report of a 62-year-old woman with systemic lupus
      erythematosus (SLE) taking rofecoxib for arthritis for 3 weeks. RESULTS: Stevens
      Johnson syndrome after 3 weeks of rofecoxib therapy. CONCLUSION: This case report
      suggests that oral rofecoxib may trigger Stevens-Johnson syndrome, potentially
      causing symblepharons, corneal neovascularization and cicatricial ectropions.

PMID- 15448506
TI  - Primary meningococcal conjunctivitis in an adult.
AB  - PURPOSE: To describe a case of primary meningococcal conjunctivitis mimicking
      epidemic keratoconjunctivitis. METHODS: Review of a case history and current
      literature. RESULTS: A 28-year-old man presented with 5 days of a bilateral
      follicular conjunctivitis and subepithelial corneal infiltrates. Initial
      diagnosis of adenoviral conjunctivitis was made. Initial Gram stain of
      conjunctival exudates was negative. Cultures grew Neisseria meningitidis.
      Systemic antibiotics were instituted with adjunctive topical therapy. The
      conjunctivitis resolved with no evidence of systemic invasion. CONCLUSIONS: The
      clinical picture of Neisseria meningitidis conjunctivitis can overlap with other
      infectious organisms including adenovirus. Early diagnosis and systemic
      antibiotic therapy are critical to prevent bacteremic spread of infection.

PMID- 15448507
TI  - Mucous membrane pemphigoid in a patient with chronic lymphocytic leukemia.
AB  - PURPOSE: To describe a case of mucous membrane pemphigoid (MMP) with ocular
      manifestations in a patient subsequently diagnosed with B-cell chronic
      lymphocytic leukemia (CLL). METHODS: Case report and literature review. RESULTS:
      A 64-year-old man presented with redness and irritation of both eyes. The patient
      also had blistering lesions on the roof of his mouth, trunk, and buttocks as well
      as bilateral conjunctival ulceration and symblepharon formation. A complete blood
      count performed before initiating treatment of presumed mucous membrane
      pemphigoid revealed a markedly increased white blood cell count (83,920) with a
      predominance of lymphocytes. Hematologic evaluation including immunophenotyping
      flow cytometry resulted in the diagnosis of B-cell chronic lymphocytic leukemia.
      Cyclophosphamide treatment improved his MMP and decreased the white blood cell
      count. CONCLUSIONS: Mucous membrane pemphigoid has been reported in association
      with a variety of nonhematologic malignancies. This case suggests that mucous
      membrane pemphigoid may also occur in B-cell CLL and supports the concept that
      autoantibodies play a role in the pathogenesis of this cicatricial conjunctival
      disease.

PMID- 15448508
TI  - Permanent corneal edema resulting from the treatment of PTK corneal haze with
      mitomycin: a case report.
AB  - A 39-year-old man underwent phototherapeutic keratectomy via excimer laser for
      recurrent corneal erosions secondary to basement membrane dystrophy with the
      subsequent development of irregular astigmatism and central stromal opacity. The
      cornea was scraped and treated with 0.02% mitomycin C using a total of 14 drops
      over a period of 6 days. Corneal edema developed as a consequence of low
      endothelial cell count with dysfunctional cells. A corneal transplant restored
      acuity of 20/20 with binocular vision. It is believed that the underlying
      endothelium was exposed to toxic doses of mitomycin C sufficient to damage and
      destroy vital cells. The author reports this case not to criticize the use of
      mitomycin C in visually disabling post-phototherapeutic keratectomy or
      photorefractive keratectomy haze but to apprize colleagues of a potential
      pitfall. The author believes that the use of mitomycin C as a 1-time application
      at the end of surgery is a safe and valuable adjunct to recover vision when no
      other is known. However, continued topical application of mitomycin C to the
      central cornea, in the face of an epithelial defect or an epithelium with
      inadequate barrier function, increases the risk of endothelial damage.

PMID- 15448509
TI  - Secondary gelatinous-like keratopathy in corneal graft.
AB  - PURPOSE: To describe the appearance of gelatinous-like keratopathy in a corneal
      graft. METHODS: A 42-year-old healthy white man underwent phacoemulsification and
      placement of a posterior chamber intraocular lens. After the procedure, he
      developed pseudophakic bullous keratopathy and underwent 2 subsequent corneal
      transplantations because of failure of the primary corneal graft. RESULTS: Over
      14 months after the second transplantation, a flower-like gelatinous keratopathy
      appeared in the corneal transplant. The patient underwent superficial
      keratectomy, removal of the continuous suture, topical application of nitomycin
      C, and placement of therapeutic contact lens until reepithelialization. The
      condition did not recur in a follow-up of 6 months. Histologically, hyperplastic
      epithelium, subepithelial fibrosis, and hyaline material were noted. CONCLUSION:
      Secondary gelatinous-like keratopathy may rarely affect corneal grafts causing a
      decrease in visual acuity. It may be a rare pathologic response to chronic
      pathophysiologic stress. Superficial keratectomy and application of topical
      mitomycin C with careful follow-up of the corneal graft may improve the visual
      outcome.

PMID- 15448511
TI  - Risk assessment and control require analysis of both outcomes and process of
      care.

PMID- 15448512
TI  - Functional brain imaging: some parameters for success.

PMID- 15448513
TI  - Malignant hyperthermia in North America: genetic screening of the three hot spots
      in the type I ryanodine receptor gene.
AB  - BACKGROUND: Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal
      muscle, manifested as a life-threatening hypermetabolic crisis after exposure to
      anesthetics. Type I ryanodine receptor 1 is the primary gene responsible for
      susceptibility to MH as well as central core disease, a congenital myopathy that
      predisposes susceptibility to MH. More than 40 mutations in the RyR1 gene cluster
      in three coding regions: the N-terminus, central, and C-terminus regions.
      However, the frequency of mutations in each region has not been studied in the
      North American MH-susceptible population. METHODS: The authors tested 124
      unrelated patients with MH susceptibility for the presence of mutations in the N
      terminus (exons 2, 6, 9, 11, 12, and 17), central (exons 39, 40, 44, 45, and 46),
      and C-terminus (exons 95, 100, 101, and 102) regions. RESULTS: Fourteen mutations
      have been identified in 29 of 124 MH-susceptible patients (23%). Approximately
      70% of the mutations, which include a novel mutation, Ala 2437Val, were in the
      central region. In 8 patients (28%), mutations were identified in the N-terminus
      region. Screening the C-terminus region yielded a novel mutation, Leu4824Pro, in
      a single patient with a diagnosis of central core disease. CONCLUSIONS: The
      detection rate for mutations is only 23% by screening mutations (or exons) listed
      in the 2002 North American consensus panel. The implications from this study
      suggest that testing the central region first is currently the most effective
      screening strategy for the North American population. Screening more exons in the
      three hot spots may be needed to find an accurate frequency of mutations in the
      RyR1 gene.

PMID- 15448514
TI  - Information loss over time defines the memory defect of propofol: a comparative
      response with thiopental and dexmedetomidine.
AB  - BACKGROUND: Sedative-hypnotic drugs impair memory, but details regarding the
      nature of this effect are unknown. The influences of propofol, thiopental, and
      dexmedetomidine on the performance of a task that isolates specific components of
      episodic memory function were measured. METHODS: Working (1 intervening item, 6
      s) and long-term memory (10 intervening items, 33 s) were tested using auditory
      words in a continuous recognition task before and during drug administration.
      Eighty-three volunteer participants were randomly assigned to receive a constant
      target concentration of drug or placebo, producing sedative effects from
      imperceptible to unresponsiveness. Responsive participants were categorized as
      high or low performers, using a median split of long-term memory performance
      during drug administration. Recognition of words at the end of the study day was
      assessed. RESULTS: High performers had acquisition of material into long-term
      memory when drug was present at the same level as placebo. Retention of this
      material at 225 min was significantly less for propofol (39 +/- 23% loss of
      material) than for other drugs (17-23% loss; P < 0.01). Greater sedation in low
      performers was evident in multiple measures. Memory for words presented before
      drug was no different from that associated with placebo for all groups.
      CONCLUSIONS: Lack of retention of material acquired into long-term memory during
      propofol administration, associated with minimal sedation, seems to define drug
      induced amnesia. Sedation seems to impair the acquisition or encoding of material
      into long-term memory. Therefore, the putative targets of drug-induced amnesia by
      propofol are processes associated with retention of material in long-term memory.

PMID- 15448515
TI  - Teaching residents pediatric fiberoptic intubation of the trachea: traditional
      fiberscope with an eyepiece versus a video-assisted technique using a fiberscope
      with an integrated camera.
AB  - BACKGROUND: The authors' hypothesis was that a video-assisted technique should
      speed resident skill acquisition for flexible fiberoptic oral tracheal intubation
      (FI) of pediatric patients because the attending anesthesiologist can provide
      targeted instruction when sharing the view of the airway as the resident attempts
      intubation. METHODS: Twenty Clinical Anesthesia year 2 residents, novices in
      pediatric FI, were randomly assigned to either the traditional group (traditional
      eyepiece FI) or the video group (video-assisted FI). One of two attending
      anesthesiologists supervised each resident during FI of 15 healthy children, aged
      1-6 yr. The time from mask removal to confirmation of endotracheal tube placement
      by end-tidal carbon dioxide detection was recorded. Intubation attempts were
      limited to 3 min; up to three attempts were allowed. The primary outcome measure,
      time to success or failure, was compared between groups. Failure rate and number
      of attempts were also compared between groups. RESULTS: Three hundred patient
      intubations were attempted; eight failed. On average, the residents in the video
      group were faster, were three times more likely to successfully intubate at any
      given time during an attempt, and required fewer attempts per patient compared to
      those in the traditional group. CONCLUSIONS: The video system seems to be
      superior for teaching residents fiberoptic intubation in children.

PMID- 15448516
TI  - Application of Bispectral Index and Narcotrend index to the measurement of the
      electroencephalographic effects of isoflurane with and without burst suppression.
AB  - BACKGROUND: The Narcotrend monitor (MonitorTechnik, Bad Bramstedt, Germany) has
      recently been introduced as an intraoperative monitor of anesthetic state, based
      on a classification scheme originally developed for visual assessment of the
      electroencephalogram. The authors compared the performance of the Narcotrend
      index (software version 4.0) to the Bispectral Index (BIS, version XP; Aspect
      Medical Systems, Natick, MA) as electroencephalographic measures of isoflurane
      drug effect during general anesthesia. METHODS: The authors observed 15 adult
      patients scheduled to undergo radical prostatectomy with a combined epidural
      isoflurane general anesthesia technique. At least 45 min after induction of
      general anesthesia, during a phase of constant surgical stimulation, end-tidal
      isoflurane concentrations were varied between 0.5 and 2.0 multiples of minimum
      alveolar concentration, and the BIS and the Narcotrend index were recorded. The
      prediction probability (PK) was calculated for the BIS and the Narcotrend index
      to predict isoflurane effect compartment concentration for each measure. The
      correlation analysis of the BIS and the Narcotrend index with the isoflurane
      effect compartment concentration was obtained by pharmacodynamic modeling based
      on two sigmoidal curves to account for the discontinuity in both indices with the
      onset of burst suppression. RESULTS: The prediction probabilities were
      indistinguishable (BIS PK = 0.72 +/- 0.07 (mean +/- SD); range, 0.61-0.84;
      Narcotrend index PK = 0.72 +/- 0.10; range, 0.51-0.87), as were the correlations
      between the electroencephalographic measures and isoflurane effect compartment
      concentrations (BIS R = 0.82 +/- 0.12; Narcotrend index R = 0.85 +/- 0.09). The
      pharmacodynamic models for the BIS and the Narcotrend index yielded nearly
      identical results. CONCLUSIONS: The BIS and the Narcotrend index detected the
      electroencephalographic effects of isoflurane equally. Combining two fractional
      sigmoid Emax models adequately described the data before and after the onset of
      burst suppression.

PMID- 15448517
TI  - Apolipoprotein E genotype and cognitive dysfunction after noncardiac surgery.
AB  - BACKGROUND: Apolipoprotein E is important in recovery after neuronal damage. The
      epsilon4 allele of the apolipoprotein E gene has been shown as a risk factor for
      Alzheimer disease, poor outcome after cerebral injury, and accelerated cognitive
      decline with normal aging. The authors hypothesized that patients with the
      epsilon4 allele would have an increased risk of postoperative cognitive
      dysfunction (POCD) after noncardiac surgery. METHODS: In a multicenter study, a
      total of 976 patients aged 40 yr and older undergoing noncardiac surgery were
      tested preoperatively and 1 week and 3 months after surgery with a
      neuropsychological test battery comprising seven subtests. POCD was defined as a
      decline in test performance of more than 2 SD from the expected. Apolipoprotein E
      genotypes were determined by blood sample analysis at a central laboratory.
      Multivariate logistic regression analysis with POCD as the dependent variable
      assessed presence of the epsilon4 allele (yes/no) and other possible risk
      factors. RESULTS: The epsilon4 allele was found in 272 patients. One week after
      surgery, the incidence of POCD was 11.7% in patients with the epsilon4 allele and
      9.9% in patients without the epsilon4 allele (P = 0.41). Three months later, POCD
      was found in 10.3% of patients with the epsilon4 allele and in 8.4% of patients
      without the epsilon4 allele (P = 0.40). Multivariate logistic regression analysis
      did not identify the epsilon4 allele as a risk factor at 1 week (P = 0.33) or 3
      months (P = 0.57). CONCLUSIONS: The authors were unable to show a significant
      association between apolipoprotein E genotype and POCD, but statistical power was
      limited because of a lower incidence of POCD than expected.

PMID- 15448518
TI  - Effects of cardiopulmonary bypass on sufentanil pharmacokinetics in patients
      undergoing coronary artery bypass surgery.
AB  - BACKGROUND: Complete pharmacokinetic modeling, including assessment of the effect
      of cardiopulmonary bypass (CPB) on sufentanil disposition, has not been reported.
      The aims of this investigation were to define a model that accurately predicted
      sufentanil concentrations during and after cardiac surgery and to determine if
      CPB had a clinically significant impact on sufentanil pharmacokinetics. METHODS:
      Population pharmacokinetic modeling was applied to data from 21 patients
      undergoing coronary artery bypass grafting. The predictive ability of models was
      assessed by calculating bias, accuracy, and measured:predicted concentration
      ratios versus time. A simple three-compartment model, without covariates, was
      initially compared with models having weight or gender as covariates and was
      subsequently used as the foundation for multiple CPB-adjusted models (allowing
      step-changes of parameters at the start or end of CPB). The primary criterion for
      choosing more complex models was a significant improvement in log-likelihood;
      secondary criteria were significant improvement in bias or accuracy. RESULTS:
      Neither covariate (weight or gender) models improved bias or accuracy compared
      with the simple three-compartment model. A final CPB-adjusted model with V2 and
      Cl3 changing at the start of CPB and V1, Cl2, and Cl3 changing at the end of CPB
      had significantly greater log-likelihood values when compared with the simple
      three-compartment model and with less elaborate CPB-adjusted models. However,
      bias and accuracy for this final model were not significantly different from the
      simple three-compartment model. CONCLUSIONS: When sufentanil is infused at a
      constant rate, with initiation of CPB, a pharmacokinetic model adjusted for CPB
      predicts that the sufentanil concentration will decrease approximately 17% and
      that it will begin to return to the prebypass concentration 12 min after
      initiation of CPB. At the end of CPB, this model also predicts a brief spike of
      the sufentanil concentration. These predictions reflect changes in the measured
      sufentanil concentrations. However, compared with a simple, three-compartment
      model, incorporating step-changes of pharmacokinetic parameters at the start or
      end of cardiopulmonary bypass (or both) did not significantly improve overall
      perioperative prediction of measured sufentanil concentrations. This suggests
      that CPB has clinically insignificant effects on sufentanil kinetics in adults.

PMID- 15448519
TI  - Do indomethacin and propofol cause cerebral ischemic damage? Diffusion-weighted
      magnetic resonance imaging in patients undergoing craniotomy for brain tumors.
AB  - BACKGROUND: Diffusion-weighted magnetic resonance imaging was used to determine
      whether indomethacin and propofol induce cerebral ischemic damage in patients
      undergoing craniotomy for cerebral tumors. As a secondary aim, the authors
      investigated whether low jugular bulb oxygen saturation values were associated
      with brain parenchymal damage as evaluated by diffusion-weighted imaging.
      METHODS: Nine patients subjected to craniotomy for supratentorial brain tumors in
      propofol-fentanyl anesthesia were studied. Magnetic resonance imaging including
      diffusion- and perfusion-weighted and structural sequences were performed (1) on
      the day before surgery, (2) before and (3) 20 min after administration of
      indomethacin (bolus of 0.2 mg/kg followed by infusion of 0.2 mg.kg.h) in the
      propofol-fentanyl-anesthetized patient, and (4) 2 days after surgery. Apparent
      diffusion coefficient maps were calculated. Jugular bulb oxygen saturation,
      arteriovenous oxygen difference, mean arterial blood pressure, and arterial
      oxygen and carbon dioxide tensions were measured simultaneously with the magnetic
      resonance examinations performed during anesthesia. RESULTS: No ischemic lesions
      were detected in the diffusion-weighted or apparent diffusion coefficient images.
      A nonsignificant decrease in jugular bulb oxygen saturation from 51% (range, 40
      61%) to 43% (range, 37-63%) and increase in arteriovenous oxygen difference from
      4.4 mm (range, 2.7-4.6 mm) to 4.7 mm (range, 2.9-5.2 mm) was observed after
      indomethacin administration. CONCLUSION: Administration of indomethacin during
      propofol anesthesia is not associated with evidence of ischemic damage in
      patients with brain tumors, as evaluated by diffusion-weighted imaging.

PMID- 15448520
TI  - A brief regional ischemic-reperfusion enhances propofol-induced depression in
      left ventricular function of in situ rat hearts.
AB  - BACKGROUND: Propofol is short-acting intravenous general anesthetics that reduces
      cardiovascular hemodynamics. The effects of propofol on intrinsic myocardial
      contractility, however, remain debatable. The aim of the current study was to
      test the hypothesis that inhibitory effects of propofol on left ventricular (LV)
      contractility and mechanical work capability of in situ ejecting rat hearts are
      attenuated after a brief regional ischemia and reperfusion. METHODS: The authors
      obtained steady-state LV pressure-volume loops and intermittently obtained LV end
      systolic pressure-volume relation and evaluated effects of propofol on LV
      function by end-systolic pressure (ESPmLVV), systolic pressure-volume area
      (PVAmLVV) at midrange LV volume (mLVV). RESULTS: Propofol (5.2 +/- 0.3
      approximately 11.1 +/- 3.7 microg.ml) significantly decreased ESP0.08 to 78 +/-
      12% approximately 64 +/- 13% of prepropofol and PVA0.08 to 76 +/-
      13%approximately 63 +/- 16% of prepropofol in normal hearts, whereas propofol at
      a lower concentration (4.1 +/- 1.0 microg/ml) did not. Although brief ischemic
      reperfusion per se did not affect LV function, propofol after that, even at a
      lower concentration (4.1 +/- 1.0 microg/ml), significantly decreased ESP0.08 to
      70 +/- 27% of prepropofol and PVA0.08 to 68 +/- 33% of prepropofol. Pretreatment
      with a protein kinase C (PKC) inhibitor, bisindolylmaleimide reduced the propofol
      (4.1 +/- 1.0 microg/ml)-induced greater decreases in ESP0.08 and PVA0.08 after
      brief ischemic-reperfusion to 94 +/- 33% and 92 +/- 39% of prepropofol. In the
      propofol-infused hearts after brief ischemic-reperfusion, protein kinase C
      epsilon translocation to the nucleus-myofibril fraction was found. CONCLUSION: In
      contrast to the study hypothesis, brief ischemic-reperfusion enhanced the
      inhibitory effects of propofol on LV systolic function; this enhancement is
      attributable to activation of protein kinase C.

PMID- 15448521
TI  - Comparative effects of bupivacaine and ropivacaine on intracellular calcium
      transients and tension in ferret ventricular muscle.
AB  - BACKGROUND: Recent evidence suggests that ropivacaine exerts markedly less
      cardiotoxicity compared with bupivacaine; however, the mechanisms are not fully
      understood at the molecular level. METHODS: Isolated ferret ventricular papillary
      muscles were microinjected with the Ca-binding photoprotein aequorin, and
      intracellular Ca transients and tension were simultaneously measured during
      twitch in the absence and presence of bupivacaine or ropivacaine. RESULTS:
      Bupivacaine and ropivacaine (10, 30, and 100 microm) reduced peak systolic [Ca]i
      and tension in a concentration-dependent manner. The effects were significantly
      greater for bupivacaine, particularly on tension (approximately twofold). The
      percentage reduction of tension was linearly correlated with that of [Ca]i for
      both anesthetics, with the slope of the relationship being approximately equal to
      1.0 for ropivacaine and approximately equal to 1.3 for bupivacaine (slope
      difference, P < 0.05), suggesting that the cardiodepressant effect of ropivacaine
      results predominantly from inhibition of Ca transients, whereas bupivacaine
      suppresses Ca transients and the reaction beyond Ca transients, i.e.,
      myofibrillar activation, as well. BAY K 8644, a Ca channel opener, abolished the
      inhibitory effects of ropivacaine on Ca transients and tension, whereas BAY K
      8644 only partially inhibited the effects of bupivacaine, particularly the
      effects on tension. CONCLUSION: The cardiodepressant effect of bupivacaine is
      approximately twofold greater than that of ropivacaine. Bupivacaine suppresses Ca
      transients more markedly than does ropivacaine and reduces myofibrillar
      activation, which may at least in part underlie the greater inhibitory effect of
      bupivacaine on cardiac contractions. These results suggest that ropivacaine has a
      more favorable profile as a local anesthetic in the clinical settings.

PMID- 15448522
TI  - Isoflurane reduces the carbachol-evoked Ca2+ influx in neuronal cells.
AB  - BACKGROUND: The authors previously reported that the isoflurane-caused reduction
      of the carbachol-evoked cytoplasmic Ca transient increase ([Ca]cyt) was
      eliminated by K or caffeine-pretreatment. In this study the authors investigated
      whether the isoflurane-sensitive component of the carbachol-evoked [Ca]cyt
      transient involved Ca influx through the plasma membrane. METHODS: Perfused
      attached human neuroblastoma SH-SY5Y cells were exposed to carbachol (1 mm, 2
      min) in the absence and presence of isoflurane (1 mm) and in the absence and
      presence of extracellular Ca (1.5 mm). The authors studied the effect of the
      nonspecific cationic channel blocker La (100 microm), of the L-type Ca channel
      blocker nitrendipine (10 microm), and of the N-type Ca channel blocker omega
      conotoxin GVIA (0.1 microm) on isoflurane modulation of the carbachol-evoked
      [Ca]cyt transient. [Ca]cyt was detected with fura-2 and experiments were carried
      out at 37 degrees C. RESULTS: Isoflurane reduced the peak and area of the
      carbachol-evoked [Ca]cyt transient in the presence but not in the absence of
      extracellular Ca. La had a similar effect as the removal of extracellular Ca.
      Omega-conotoxin GVIA and nitrendipine did not affect the isoflurane sensitivity
      of the carbachol response although nitrendipine reduced the magnitude of the
      carbachol response. CONCLUSIONS: The current data are consistent with previous
      observations in that the carbachol-evoked [Ca]cyt transient involves both Ca
      release from intracellular Ca stores and Ca entry through the plasma membrane. It
      was found that isoflurane attenuates the carbachol-evoked Ca entry. The
      isoflurane sensitive Ca entry involves a cationic channel different from the L-
      or N- type voltage-dependent Ca channels. These results indicate that isoflurane
      attenuates the carbachol-evoked [Ca]cyt transient at a site at the plasma
      membrane that is distal to the muscarinic receptor.

PMID- 15448523
TI  - Local anesthetics reduce mortality and protect against renal and hepatic
      dysfunction in murine septic peritonitis.
AB  - BACKGROUND: Mortality from sepsis frequently results from multiple organ injury
      and dysfunction. Cecal ligation and puncture is an established murine model of
      septic peritonitis that produces septic shock characterized by an initial
      hyperinflammatory response. In addition to their anesthetic properties, local
      anesthetics have been shown to attenuate inflammatory responses both in vivo and
      in vitro. In the current study, the ability of local anesthetic infusions to
      protect against sepsis-induced mortality, as well as renal and hepatic
      dysfunction after cecal ligation and puncture, was investigated. METHODS: C57BL/6
      mice received mini-osmotic pumps containing saline (vehicle), 10% lidocaine, or
      1% bupivacaine and were subjected to cecal ligation and puncture. Twenty-four
      hours after cecal ligation and puncture, renal and hepatic functions were
      assessed as well as markers of inflammation (proinflammatory cytokine protein and
      mRNA concentrations and myeloperoxidase activity). Renal apoptosis and 7-day
      survival was also assessed. RESULTS: Mice treated with lidocaine or bupivacaine
      infusion showed improved survival and had significantly lower plasma creatinine,
      aspartate aminotransferase, and alanine aminotransferase concentrations compared
      with mice receiving vehicle alone. Significant reduction in plasma tumor necrosis
      factor-alpha and keratinocyte-derived chemokine, as well as reductions in
      myeloperoxidase activity, intracellular adhesion molecule-1 protein expression,
      mRNA concentrations of proinflammatory markers, and apoptosis were observed in
      renal cortices from both local anesthetic groups. CONCLUSIONS: The current data
      demonstrate that local anesthetic infusions confer a protective effect in mice
      from septic peritonitis by attenuating the hyperacute inflammatory response. This
      suppression resulted in improved mortality and less progression to acute kidney
      and liver injury and dysfunction.

PMID- 15448524
TI  - Influence of propofol on neuronal damage and apoptotic factors after incomplete
      cerebral ischemia and reperfusion in rats: a long-term observation.
AB  - BACKGROUND: Propofol reduces neuronal damage from cerebral ischemia when
      investigated for less than 8 postischemic days. This study investigates the long
      term effects of propofol on neuronal damage and apoptosis-related proteins after
      cerebral ischemia and reperfusion. METHODS: Male Sprague-Dawley rats were
      randomly assigned as follows: group 1 (n = 32, control): fentanyl and nitrous
      oxide-oxygen; group 2 (n = 32, propofol): propofol and oxygen-air. Ischemia (45
      min) was induced by carotid artery occlusion and hemorrhagic hypotension.
      Pericranial temperature and arterial blood gases were maintained constant. After
      1, 3, 7, and 28 postischemic days, brains were removed, frozen, and sliced.
      Hippocampal eosinophilic cells were counted. The amount of apoptosis-related
      proteins Bax, p53, Bcl-2, and Mdm-2 and neurons positive for activated caspase-3
      were analyzed. RESULTS: In propofol-anesthetized rats, no eosinophilic neurons
      were detected, whereas in control animals, 16-54% of hippocampal neurons were
      eosinophilic (days 1-28). In control animals, the concentration of Bax was 70
      200% higher after cerebral ischemia compared with that in animals receiving
      propofol over time. Bcl-2 was 50% lower in control animals compared with propofol
      anesthetized rats during the first 3 days. In both groups, a maximal 3% of the
      hippocampal neurons were positive for activated caspase-3. CONCLUSIONS: These
      data show sustained neuroprotection with propofol. This relates to reduced
      eosinophilic and apoptotic injury. Activated caspase-3-dependent apoptotic
      pathways were not affected by propofol. This suggests the presence of activated
      caspase-3-independent apoptotic pathways.

PMID- 15448525
TI  - Remifentanil preconditioning protects against ischemic injury in the intact rat
      heart.
AB  - BACKGROUND: Opioid receptors mediate cardiac ischemic preconditioning.
      Remifentanil is a new, potent ultra-short-acting phenylpiperidine opioid used in
      high doses for anesthesia. The authors hypothesize that pretreatment with this
      drug confers cardioprotection. METHODS: Male Sprague-Dawley rats were
      anesthetized and the chest was opened. All animals were subjected to 30 min of
      occlusion of the left coronary artery and 2 h of reperfusion. Before the 30-min
      occlusion, rats received either preconditioning by ischemia (ischemic
      preconditioning, 5-min occlusion, 5-min reperfusion x 3) or pretreatment with
      remifentanil, performed with the same regime (3 x 5-min infusions) using 0.2,
      0.6, 2, 6, or 20 microg.kg.min intravenously. The experiment was repeated with
      naltrindole (a selective Delta-opioid receptor antagonist, 5 mg/kg),
      norbinaltorphimine (a selective kappa-OR antagonist, 5 mg/kg), or CTOP (a
      selective mu-opioid receptor antagonist, 1 mg/kg) administered before
      remifentanil-induced preconditioning or ischemic preconditioning, respectively.
      Infarct size, as a percentage of the area at risk, was determined by 2,3,5
      triphenyltetrazolium staining. RESULTS: There was a dose-related reduction in
      infarct size/area at risk after treatment with remifentanil that was similar to
      that seen with ischemic preconditioning. This effect was prevented or
      significantly attenuated by coadministration of a mu, kappa, or Delta-opioid
      antagonist. The infarct-sparing effect of ischemic preconditioning was abolished
      by blockade of kappa-opioid receptors or Delta-opioid receptors but not by mu
      opioid receptors. CONCLUSION: Remifentanil mimics cardioprotection via all three
      opioid receptors. This differs from ischemic preconditioning, which confers
      cardioprotection via kappa- and Delta-, but not mu-opioid receptors. Part of the
      protective effect of remifentanil may be produced by mu-agonist activity outside
      the heart.

PMID- 15448526
TI  - Influence of GABAA receptor gamma2 splice variants on receptor kinetics and
      isoflurane modulation.
AB  - BACKGROUND: Gamma-aminobutyric acid type A (GABAA) receptors, the major
      inhibitory receptors in the brain, are important targets of many drugs, including
      general anesthetics. These compounds exert multiple effects on GABAA receptors,
      including direct activation, prolongation of deactivation kinetics, and reduction
      of inhibitory postsynaptic current amplitudes. However, the degree to which these
      actions occur differs for different agents and synapses, possibly because of
      subunit-specific effects on postsynaptic receptors. In contrast to
      benzodiazepines and intravenous anesthetics, there is little information
      available about the subunit dependency of actions of volatile anesthetics.
      Therefore, the authors studied in detail the effects of isoflurane on recombinant
      GABAA receptors composed of several different subunit combinations. METHODS:
      Human embryonic kidney 293 cells were transiently transfected with rat
      complementary DNAs of alpha1beta2, alpha1beta2gamma2L, alpha1beta2gamma2S,
      alpha5beta3, or alpha5beta3gamma2S subunits. Using rapid application and whole
      cell patch clamp techniques, cells were exposed to 10- and 2,000-ms pulses of
      gamma-aminobutyric acid (1 mm) in the presence or absence of isoflurane (0.25,
      0.5, 1.0 mm). Anesthetic effects on decay kinetics, peak amplitude, net charge
      transfer and rise time were measured. Statistical significance was assessed using
      the Student t test or one-way analysis of variance followed by the Tukey post hoc
      test. RESULTS: Under control conditions, incorporation of a gamma2 subunit
      conferred faster deactivation kinetics and reduced desensitization. Isoflurane
      slowed deactivation, enhanced desensitization, and reduced peak current amplitude
      in alphabeta receptors. Coexpression with a gamma2 subunit caused these effects
      of isoflurane to be substantially reduced or abolished. Although the two gamma2
      splice variants imparted qualitatively similar macroscopic kinetic properties,
      there were significant quantitative differences between effects of isoflurane on
      deactivation and peak current amplitude in gamma2S- versus gamma2L-containing
      receptors. The net charge transfer resulting from brief pulses of gamma
      aminobutyric acid was decreased by isoflurane in alphabeta but increased in
      alphabetagamma receptors. CONCLUSIONS: The results indicate that subunit
      composition does substantially influence modulation of GABAA receptors by
      isoflurane. Specifically, the presence of a gamma2 subunit and the identity of
      its splice variant are important factors in determining physiologic and
      pharmacologic properties. These results may have functional implications in
      understanding how anesthetic effects on specific types of GABAA receptors in the
      brain contribute to changes in brain function and behavior.

PMID- 15448527
TI  - Effect of bupivacaine on the isolated rabbit heart: developmental aspect on
      ventricular conduction and contractility.
AB  - BACKGROUND: Newborns and infants seem to be at greater risk of bupivacaine
      cardiotoxicity than adults do. Few experiments have studied the effects of local
      anesthetics on myocardium associated with developmental changes, and their
      conclusions are conflicting. The authors compared the effects of bupivacaine on
      an isolated heart preparation in newborn and adult rabbits. METHODS: The authors
      used a constant-flow, nonrecirculating Langendorff preparation paced atrially.
      Adult and newborn rabbit hearts were exposed to step-increasing concentrations of
      bupivacaine. For each concentration, heart rate was modified with pacing from 180
      to 360 beats/min by increments of 30 beats/min. QRS complex duration (index of
      ventricular conduction) and the first derivative of left ventricular pressure
      (index of contractility) were measured. The two groups were compared using an
      Emax model. RESULTS: In newborn and adult rabbits, QRS complex duration increased
      with increasing bupivacaine concentration. No difference was observed between
      neonatal and adult hearts. Contractility decreased with increasing bupivacaine
      concentration. Newborn rabbits were approximately three times more sensitive than
      adult rabbits to the effects of bupivacaine. However, the concentration leading
      to 50% decrease in the first derivative of left ventricular pressure was much
      higher than the concentration leading to half maximum increase in QRS complex
      duration. CONCLUSIONS: In conclusion, using a whole organ preparation, the
      authors demonstrated that bupivacaine induces similar impairment in ventricular
      conduction in newborn and adult rabbits. In particular, the tonic and the phasic
      blocks were of similar intensity in both groups. Conversely, the effect of
      bupivacaine on contractility was markedly higher in newborn rabbits than in adult
      rabbits. Also, contractility was less impaired than ventricular conduction in
      both groups.

PMID- 15448528
TI  - Topical humidified carbon dioxide to keep the open surgical wound warm: the
      greenhouse effect revisited.
AB  - BACKGROUND: Perioperative hypothermia is common in open surgery and is associated
      with increased rates of wound infection. This is a result of decreased wound
      tissue oxygenation, which can be normalized by local warming. Recently, a
      technique has been developed to establish a carbon dioxide atmosphere in an open
      surgical wound. Therefore, the authors studied the possible "greenhouse effect"
      of carbon dioxide insufflation and operation lamps on wound temperature. METHODS:
      In a fully ventilated operating room surface temperature was measured at steady
      state in a model of an open surgical wound containing blood agar. The wound model
      was randomized to either no insufflation or insufflation of dry and humidified
      carbon dioxide or air, respectively, at a flow of 5 l/min via a gas diffuser. The
      surface temperature was measured with operation lamps switched on and off,
      respectively. Evaporation rates were also measured. RESULTS: With the operation
      light off, the surface temperature in the control was 31.8 degrees C, and with
      the operation light on, the temperature increased by 1.5 degrees C (P < 0.001).
      Additional insufflation of dry carbon dioxide increased the surface temperature
      another 1.9 degrees C (P < 0.001). When the carbon dioxide was humidified, the
      evaporation rate was lowest and the surface temperature increased further to 35.6
      degrees C (P = 0.002). In contrast, insufflation of dry and humidified air did
      not have a significant effect on the evaporation rate and only marginally
      increased the wound temperature in comparison with the control. CONCLUSIONS:
      Insufflation of humidified carbon dioxide in combination with light from the
      operation lamps may help to keep the open wound warm during surgery.

PMID- 15448529
TI  - Severe neurological complications after central neuraxial blockades in Sweden
      1990-1999.
AB  - BACKGROUND: Central neuraxial blockades find widespread applications. Severe
      complications are believed to be extremely rare, but the incidence is probably
      underestimated. METHODS: A retrospective study of severe neurologic complications
      after central neuraxial blockades in Sweden 1990-1999 was performed. Information
      was obtained from a postal survey and administrative files in the health care
      system. During the study period approximately 1,260,000 spinal blockades and
      450,000 epidural blockades were administered, including 200,000 epidural
      blockades for pain relief in labor. RESULTS: : The 127 complications found
      included spinal hematoma (33), cauda equina syndrome (32), meningitis (29),
      epidural abscess (13), and miscellaneous (20). Permanent neurologic damage was
      observed in 85 patients. Incidence of complications after spinal blockade was
      within 1:20-30,000 in all patient groups. Incidence after obstetric epidural
      blockade was 1:25,000; in the remaining patients it was 1:3600 (P < 0.0001).
      Spinal hematoma after obstetric epidural blockade carried the incidence
      1:200,000, significantly lower than the incidence 1:3,600 females subject to knee
      arthroplasty (P < 0.0001). CONCLUSIONS: : More complications than expected were
      found, probably as a result of the comprehensive study design. Half of the
      complications were retrieved exclusively from administrative files. Complications
      occur significantly more often after epidural blockade than after spinal
      blockade, and the complications are different. Obstetric patients carry
      significantly lower incidence of complications. Osteoporosis is proposed as a
      previously neglected risk factor. Close surveillance after central neuraxial
      blockade is mandatory for safe practice.

PMID- 15448530
TI  - Functional magnetic resonance imaging studies of pain: an investigation of signal
      decay during and across sessions.
AB  - BACKGROUND: Several investigations into brain activation caused by pain have
      suggested that the multiple painful stimulations used in typical block designs
      may cause attenuation over time of the signal within activated areas. The effect
      this may have on pain investigations using multiple tasks has not been
      investigated. The signal decay across a task of four repeating pain stimulations
      and between two serial pain tasks separated by a 4-min interval was examined to
      determine whether signal attenuation may significantly confound pain
      investigations. METHODS: The characteristics of the brain activation of six
      subjects were determined using whole brain blood oxygenation level-dependent
      functional magnetic resonance imaging on a 1.5-T scanner. Tasks included both
      tingling and pain induced by transcutaneous electrical stimulation of the median
      nerve. The average group maps were analyzed by general linear modeling with
      corrected cluster P values of less than 0.05. The time courses of individual
      voxels were further investigated by analysis of variance with P values of less
      than 0.05. RESULTS: Significant differences between pain and tingling were found
      in the ipsilateral cerebellum, contralateral thalamus, secondary somatosensory
      cortex, primary somatosensory cortex, and anterior cingulate cortex. Highly
      significant signal decay was found to exist across each single pain task, but the
      signal was found to be restored after a 4-min rest period. CONCLUSIONS: This work
      shows that serial pain tasks can be used for functional magnetic resonance
      imaging studies using electrical nerve stimulation as a stimulus, as long as
      sufficient time is allowed between the two tasks.

PMID- 15448531
TI  - Popliteal sciatic perineural local anesthetic infusion: a comparison of three
      dosing regimens for postoperative analgesia.
AB  - BACKGROUND: This randomized, double-blind study investigated the efficacy of
      continuous and patient-controlled ropivacaine infusion via a popliteal sciatic
      perineural catheter in ambulatory patients undergoing moderately painful
      orthopedic surgery of the foot or ankle. METHODS: Preoperatively, patients (n =
      30) received a posterior popliteal sciatic perineural catheter and nerve block.
      Postoperatively, patients were discharged home with a portable infusion pump
      delivering 0.2% ropivacaine (500 ml) in one of three dosing regimens: the basal
      group (12-ml/h basal rate, 0.05-ml patient-controlled bolus dose), the basal
      bolus group (8-ml/h basal rate, 4-ml bolus dose), or the bolus group (0.3-ml/h
      basal rate, 9.9-ml bolus dose). RESULTS: The bolus group experienced an increase
      in baseline pain, breakthrough pain incidence and intensity, and sleep
      disturbances compared with the other two groups (P < 0.05 for all comparisons).
      Compared with the basal-bolus group, the basal group experienced an increase in
      these outcome measures only after local anesthetic reservoir exhaustion, which
      occurred earlier than in the other two groups (P < 0.05 for all comparisons).
      Satisfaction scores did not differ among the three groups. CONCLUSIONS: This
      study demonstrates that when providing analgesia with 0.2% ropivacaine via a
      popliteal sciatic perineural catheter after moderately painful surgery of the
      foot or ankle, a continuous infusion is required to optimize infusion benefits.
      Furthermore, adding patient-controlled bolus doses allows for a lower continuous
      basal rate and decreased local anesthetic consumption and thereby increases the
      duration of infusion benefits when in an ambulatory environment with a limited
      local anesthetic reservoir.

PMID- 15448532
TI  - Chronopharmacology of intrathecal sufentanil for labor analgesia: daily
      variations in duration of action.
AB  - BACKGROUND: The pharmacokinetic and pharmacodynamic characteristics of opioids
      vary throughout the day, as demonstrated for oral morphine in chronic pain.
      However, little is known about the chronobiology of intrathecal lipid soluble
      opioids used for labor analgesia. The aim of this prospective study was to
      determine whether the duration of action of intrathecally administered sufentanil
      is influenced by the time of administration. METHODS: Ninety-one women in the
      first stage of labor were enrolled. Labor analgesia was first provided by 10
      microg intrathecal sufentanil. The duration of action of intrathecal sufentanil
      was measured and analyzed by the cosinor method to determine periodic intraday
      variation. RESULTS: Pain assessed by a visual analog score was not different
      among patients (70 +/- 17 mm) before the injection of intrathecal sufentanil.
      Rhythm analysis revealed a mean ( +/- SD) duration of analgesia (mesor) of 93.0
      +/- 3.8 min. A highly significant 12-h rhythm was found, with two peaks: One was
      near midnight (0.78 +/- 0.6 h), and the other was near noon (12.78 +/- 0.6 min)
      (P < 0.01). The amplitude of this 12-h component was 16.1 +/- 5.5 min.
      CONCLUSIONS: The duration of intrathecal sufentanil analgesia exhibited a
      temporal pattern with 30% variations throughout the day period. The authors point
      out that the lack of consideration of chronobiological conditions in
      intrathecally administered analgesia studies can cause significant statistical
      bias. Further studies dealing with intrathecal opioids should consider the time
      of drug administration.

PMID- 15448533
TI  - Contribution of interaction between nitric oxide and cyclooxygenases to the
      production of prostaglandins in carrageenan-induced inflammation.
AB  - BACKGROUND: Nitric oxide (NO) and prostaglandins (PGs) are crucial mediators
      contributing to generation of inflammatory responses and pain. This study was
      designed to investigate the effects of peripherally released NO on cyclooxygenase
      (COX) expression/activation and production of PGs in carrageenan-induced
      inflammation. METHODS: A microdialysis probe was implanted subcutaneously into
      the skin of hind paws of rats. The concentrations of NO metabolites, PGE2, and 6
      keto-PGF1alpha (metabolite of PGI2) in the dialysate were measured. Carrageenan
      was injected into the plantar surface of the hind paw during perfusion of the
      dialysis catheter with modified Ringer's solution or N-monomethyl-L-arginine
      acetate. In addition, the effects of the selective COX-1 inhibitor SC-560 and the
      selective COX-2 inhibitor NS-398 on the production of NO, PGE2, and 6-keto
      PGF1alpha were examined. Western blotting was performed to evaluate the
      expression of COX-1 and COX-2 in the skin at the site of the inflammation.
      RESULTS: Carrageenan injection resulted in increases in the concentrations of NO,
      PGE2, and PGI2, and these increases were completely suppressed by N-monomethyl-L
      arginine acetate. SC-560 effectively inhibited the increase in PGE2 and PGI2
      concentrations for the first 2 h, and NS-398 inhibited 3-6 h after carrageenan.
      Western blot analysis showed that the concentrations of both COX-1 and COX-2 in
      the skin increased after carrageenan. The up-regulation of COX-1 in the skin was
      observed 3 and 6 h after carrageenan and was not suppressed in the rats treated
      with N-monomethyl-L-arginine acetate. The up-regulation of COX-2 in the skin was
      also observed 3 and 6 h after carrageenan and was completely suppressed in the
      rats treated with N-monomethyl-L-arginine acetate. CONCLUSION: The results of the
      current study suggest that NO activates COX-1 in the early phase of carrageenan
      and up-regulates COX-2 expression in the late phase in the skin, resulting in
      production of PGE2 and PGI2 at the site of inflammation, which would contribute
      to exacerbation of the inflammatory process.

PMID- 15448534
TI  - Influence of the type of anesthesia provider on costs of labor analgesia to the
      Texas Medicaid program.
AB  - BACKGROUND: The Texas Medicaid Program (Medicaid) defines billable time for labor
      analgesia as face-to-face time; therefore, anesthesia providers determine billed
      time. The authors' goal was to determine the influence of anesthesia providers on
      labor analgesia costs billed to Medicaid. METHODS: Under the Freedom of
      Information Act, Medicaid provided data on claims paid for 6 months in 2001 for
      labor analgesia administered during the course of a vaginal delivery. Claims were
      either time based (codes 00946 or 00955) or a flat fee (codes 26311 or 26319).
      Using modifiers, the authors grouped time-based claims as either anesthesiologist
      group or certified registered nurse anesthetist (CRNA) group. The cost to
      Medicaid was based on the 2001 fee schedule. The conversion factor was 18.21 USD
      per American Society of Anesthesiologists unit. The flat-fee reimbursement was
      152.50 USD. CRNA services were paid at 85% of the fee schedule. Average time per
      time claim, percent of providers with more than 4 h of billed time, and cost per
      claim were determined for each group. Providers with more than 120 claims (> 20
      claims/month) were considered high-volume. RESULTS: The database included 21,378
      claims (anesthesiologist group: 12,698 claims from 219 providers; CRNA group:
      8,680 claims from 117 providers). For time-based claims, the average time per
      case was significantly higher in the CRNA group (146 min) than in the
      anesthesiologist group (105 min). The CRNA group cost to Medicaid (225.11 USD)
      was 19% more per claim than the anesthesiologist group (189.26 USD). The
      difference in cost per claim was greater among high-volume providers--213.10 USD
      for the CRNA group versus 168.76 USD for the anesthesiologist group. If a flat
      fee program were instituted using the average cost per claim for all groups
      (203.81 USD), the Texas Medicaid program would save more than 500,000 USD
      annually. CONCLUSIONS: The costs of labor analgesia billed to Texas Medicaid were
      19% to 26% less per patient when provided by anesthesiologists than by CRNAs,
      despite lower per-unit reimbursement of CRNAs.

PMID- 15448535
TI  - Excitation-contraction coupling in the heart and the negative inotropic action of
      volatile anesthetics.

PMID- 15448536
TI  - From continuous positive-pressure breathing to ventilator-induced lung injury.
AB  - Continuous positive-pressure ventilation in acute respiratory failure. By Kumar
      A, Falke KJ, Geffin B, Aldredge CF, Laver MB, Lowentein E, Pontoppidan H. N Engl
      J Med 1970; 283:1430-6. Reprinted with permission. Continuous positive-pressure
      ventilation was used in eight patients with severe acute respiratory failure.
      Cardiac output and lung function were studied during continuous positive-pressure
      ventilation (mean end-expiratory pressure, 13 cm H2O) and a 30-min interval of
      intermittent positive-pressure ventilation. Although the mean cardiac index
      increased from 3.6 to 4.5 l/min per square meter of body surface area, the mean
      intrapulmonary shunt increased by 9% with changeover to intermittent positive
      pressure ventilation. Satisfactory oxygenation was maintained in all patients
      during continuous positive-pressure ventilation with 50% inspired oxygen or less.
      With intermittent positive-pressure ventilation, arterial oxygen tension promptly
      fell by 161 mm of mercury, 79% occurring within 1 min. Prevention of air-space
      collapse during expiration and an increase in functional residual capacity
      probably explain improved oxygenation with continuous positive-pressure
      ventilation. In four patients, subcutaneous emphysema or pneumothorax developed.
      Weighed against the effects of prolonged hypoxemia, these complications were not
      severe enough to warrant cessation of continuous positive-pressure ventilation.

PMID- 15448537
TI  - Inductive warming of intravenous fluids: overheating of the toroid heating
      element during rapid infusion.

PMID- 15448539
TI  - Vasopressin for hemodynamic rescue in catecholamine-resistant vasoplegic shock
      after resection of massive pheochromocytoma.

PMID- 15448540
TI  - Anaphylactic shock: is vasopressin the drug of choice?

PMID- 15448541
TI  - Intraneural injection during anterior approach for sciatic nerve block.

PMID- 15448542
TI  - Effect of cyclooxygenase-1 inhibition in postoperative pain is developmentally
      regulated.

PMID- 15448543
TI  - Cardiac toxicity from 3% 2-chlorprocaine.

PMID- 15448545
TI  - Postpartum hemorrhage is not the only setting for maternal myocardial ischemia.

PMID- 15448546
TI  - High incidence of myocardial ischemia during postpartum hemorrhage or poor
      management of hemorrhagic shock?

PMID- 15448548
TI  - Do alpha agonists increase venous return?

PMID- 15448550
TI  - Anesthesia and multiorgan protein remodeling.

PMID- 15448552
TI  - Intraservice time is not a proxy for operating room time.

PMID- 15448554
TI  - A word on hypothermic preconditioning.

PMID- 15448557
TI  - Lack of tolerance with propofol in radiation therapy needs patience.

PMID- 15448558
TI  - Is it in the episcleral space or in the medial canthal extraconal space?

PMID- 15448560
TI  - Three arguments regarding a paradigm of general anesthesia.

PMID- 15448562
TI  - A sigh is not a sigh, as PEEP blows by.

PMID- 15448564
TI  - Monitoring direct thrombin inhibitors: time for standardization.

PMID- 15448565
TI  - "Oily" streak formation on aspiration of cerebrospinal fluid into local
      anesthetic solution: its significance in the combined spinal-epidural technique.

PMID- 15448566
TI  - When patients follow commands.

PMID- 15448567
TI  - Learning aid for geometric relations of cardiac valves.

PMID- 15448568
TI  - Amateur dentistry and the anesthesiologist.

PMID- 15448569
TI  - A novel maneuver used to rule out intraarterial placement of the introducer
      sheath in a patient with an ipsilateral mature forearm hemodialysis fistula.

PMID- 15448570
TI  - Detection of gas embolism by bispectral index and entropy monitoring in two
      cases.

PMID- 15448572
TI  - Spasticity: the misunderstood part of the upper motor neuron syndrome.
AB  - Spasticity is a sensorimotor phenomenon related to the integration of the nervous
      system motor responses to sensory input. Although most commonly considered a
      velocity-dependent increase to tonic stretch, it is related to hypersensitivity
      of the reflex arc and changes that occur within the central nervous system, most
      notably, the spinal cord. Injury to the central nervous system results in loss of
      descending inhibition, allowing for the clinical manifestation of abnormal
      impulses. Muscle activity becomes overactive. This is mediated at several areas
      of the stretch-reflex pathway. Although spasticity is part of the upper motor
      neuron syndrome, it is frequently tied to the other presentations of the said
      syndrome. Contracture, hypertonia, weakness, and movement disorders can all
      coexist as a result of the upper motor neuron syndrome. Although basic science
      descriptions of spasticity are being elucidated, clinically, confusion exists.

PMID- 15448573
TI  - Neurophysiologic evaluation of spastic hypertonia: implications for management of
      the patient with the intrathecal baclofen pump.
AB  - A number of techniques attempt to objectively quantify various clinical
      characteristics associated with spastic hypertonia and related motor disorders.
      These range in cost, complexity, physiologic basis of measured response, and
      invasiveness. With a greater range of treatment options for spasticity and an
      increase in the number of centers participating in studies of interventions for
      spasticity, published reports reflect increasing use of objective quantification
      techniques. We review studies that highlight the potential utility of
      neurophysiologic techniques, including the H-reflex, F-wave, and flexion
      withdrawal reflex, in the objective evaluation of response to intrathecal
      baclofen administration. The accumulated knowledge suggests that neurophysiologic
      evaluation is useful for assessing spinal cord responsiveness, and we recommend
      it as an adjunct to clinical evaluation when judging the overall effectiveness of
      intrathecal baclofen administration.

PMID- 15448574
TI  - Instrumented assessment of muscle overactivity and spasticity with dynamic
      polyelectromyographic and motion analysis for treatment planning.

PMID- 15448575
TI  - Botulinum toxin: dosing and dilution.
AB  - In the United States, the popularity of botulinum toxins as agents to treat
      muscle hypertonia has grown significantly over the last decade, despite lack of
      approval from the Food and Drug Administration for the indication of spasticity.
      Botox (botulinum toxin type A) and Myobloc (botulinum toxin type B) are Food and
      Drug Administration-approved for other indications, such as cervical dystonia.
      Another commercial preparation of type A, Dysport, has yet to reach the United
      States market as of this writing. Although botulinum toxin's efficacy in
      influencing spastic hypertonia is well accepted, the impact of certain clinical
      issues, such as dosing and dilution, on treatment outcome is not well established
      by published studies. This article will review important articles and selected
      abstracts on the use of botulinum toxin, specifically for spastic hypertonia in
      adults, with emphasis on current clinical practices as they relate to dosing and
      dilution.

PMID- 15448576
TI  - Targeting the neuromuscular junction in skeletal muscles.
AB  - Botulinum neurotoxins selectively weaken skeletal muscle by presynaptic blockade
      of vesicles containing the neurotransmitter acetylcholine. Because the location
      of the neuromuscular junction (found in motor endplates) is most highly
      concentrated in a band within the midbelly of the muscle, injection of botulinum
      neurotoxins are hypothesized to be more potent when specifically targeted toward
      the motor endplate zones. Few studies have attempted to describe the distribution
      of motor endplate zones in skeletal muscles, and scant experimental data exist
      that directly tests this hypothesis. In this article, a rationale is presented
      for motor endplate targeting within specific limb muscles with respect to
      botulinum neurotoxin therapy.

PMID- 15448577
TI  - The role of therapy in spasticity management.
AB  - A number of different therapy interventions and modalities have been utilized in
      spasticity management. There is significant variation in the use of these
      therapies, which is often due to experience that the treating clinicians have
      with one type or another. Given the lack of well controlled studies, it is
      difficult to take an evidence-based approach regarding the use of these
      interventions at this time. This article examines the physiologic basis for the
      more common therapy interventions in the management of spasticity and discusses
      some of the literature that may help guide the clinician in choosing among these
      options.

PMID- 15448578
TI  - Antispasticity medications: uses and limitations of enteral therapy.

PMID- 15448579
TI  - Botulinum toxin A injections in children: technique and dosing issues.
AB  - Information is presented on the current state of administering botulinum toxin A
      injections in the pediatric population based on review of scientific publications
      cited in MEDLINE and PubMed that involved the use of botulinum toxin A in
      patients under the age of 19. Studies were selected if they contained nearly
      complete information on botulinum toxin dosing and injection technique within the
      article. In addition, consensus articles from pediatric task forces were selected
      for review. Information regarding botulinum toxin A dosing and injection
      technique was gathered from the material and method sections of the selected
      studies or from tables in consensus articles. Information was collected in regard
      to the total amount of botulinum toxin used, commercial brand of botulinum toxin
      used, dilution of the toxin, volume of toxin preparation, needle size,
      localization technique, adverse reactions, and whether sedation was used. There
      is currently a range of dosing and injections techniques in the literature when
      using botulinum toxin A in children. Body weight, muscle size, location of
      muscle, and degree of spasticity are all considered to determine total amount of
      botulinum toxin injected. Concentration and volume of the diluted toxin can
      affect the amount of spread of the toxin after injection. Injection techniques
      also vary and are not well reported. Use of electromyographic, electrical
      stimulation, or ultrasound guidance is employed in children for difficult to
      locate individual muscle groups. Use of sedation also varies between medical
      centers.

PMID- 15448580
TI  - Optimizing treatment in social phobia: a review of treatment resistance.
AB  - Over the last 25 years, there has been a rapid expansion of our knowledge base of
      social phobia (SP). Although there are a number of well-validated treatment
      modalities, including pharmacotherapy and cognitive-behavioral therapy,
      significant gaps remain in our ability to achieve full remission in most
      patients. Despite advances in the neurobiology of SP, the etiology has yet to be
      determined. Investigations examining potential predictors of response have
      provided little guidance in selecting an appropriate treatment modality. These
      gaps in our knowledge have pushed us to examine issues related to treatment
      resistance. This paper presents a review of the current literature and issues
      related to treatment-resistant SP, including a discussion of the functional
      impairment associated with SP, definitions of treatment response and remission,
      as well as outcome measures that have been used in clinical investigations of SP.
      In addition, criteria for a standard treatment trial, predictors of treatment
      response, a review of treatment resistance studies, and potential directions for
      future research are examined. The most promising strategies to attain remission,
      will likely involve augmenting selective serotonin reuptake inhibitors or
      serotonin-norepinephrine reuptake inhibitors with agents such as anticonvulsants,
      benzodiazepines, and antipsychotics as well as combining pharmacotherapy with
      cognitive-behavioral therapy. Our current treatment target of simply attaining a
      response needs to be refocused, so that an asymptomatic state and high end state
      functioning become the final goal of treatment.

PMID- 15448581
TI  - Easing the burden: treating refractory anxiety.

PMID- 15448582
TI  - Unresolved questions about treatment-resistant anxiety disorders.

PMID- 15448583
TI  - Generalized anxiety disorder: acute and chronic treatment.
AB  - Clinical and epidemiological data suggest that generalized anxiety disorder (GAD)
      is a chronic illness causing patients to suffer for many years leading to
      significant distress in daily life functioning. The literature suggests the
      several conclusions. GAD is a disorder in need of appropriate treatment and often
      has a chronic course with comorbid conditions, such as major depression and other
      anxiety disorders. Benzodiazepines, while effective anxiolytic agents acutely,
      when prescribed for >4 weeks cause rebound anxiety and following prolonged
      therapy may lead to withdrawal symptoms. Antidepressants cause significant
      anxiety relief compared with placebo and for psychosocial treatment cognitive
      behavioral therapy is an efficacious psychosocial treatment. Many GAD patients
      are in need of long-term medication management. Furthermore, there is limited
      data for patients diagnosed with GAD the treatment outcome with the combination
      of medication and psychotherapy both acutely and long-term; how to best sequence
      these treatments; for those patients who do not meet remission criteria what is
      the ideal approach for augmentation; and for patients with treatment-refractory
      GAD the empirical evidence is lacking on medication switching and augmentation
      strategies. Research is needed in the area of developing treatment strategies for
      patients suffering from treatment-refractory GAD. There is still an urgent need
      to explore treatment combinations and duration strategies in the management of
      patients suffering with GAD.

PMID- 15448584
TI  - Treatment-resistant panic disorder.
AB  - A substantial number of patients with panic disorder and agoraphobia may remain
      symptomatic after standard treatment (including selective serotonin reuptake
      inhibitors, tricyclic antidepressants, benzodiazepines, or irreversible monamine
      oxidase inhibitors). In this review, recommendations for the treatment of
      patients with panic disorder and agoraphobia who do not respond to these drugs
      are provided. Nonresponse to drug treatment could be defined as a failure to
      achieve a 50% reduction on a standard rating scale after a minimum of 6 weeks of
      treatment in adequate dose. When initial treatments have failed, the medication
      should be changed to other standard treatments. In further attempts at treatment,
      drugs should be used that have shown promising results in preliminary studies,
      such as venlafaxine. Combination treatments may be used, such as the combination
      of an selective serotonin reuptake inhibitor and a benzodiazepine. Psychological
      treatments such as cognitive-behavioral therapy have to be considered in all
      patients, regardless whether they are nonresponders or not. According to existing
      studies, a combination of pharmacologic treatment with cognitive-behavioral
      therapy can be recommended.

PMID- 15448585
TI  - Treatment-resistant posttraumatic stress disorder: strategies for intervention.
AB  - The mainstay of treatment for chronic posttraumatic stress disorder (PTSD) is a
      combination of psychotherapy and medication treatments. The first-line
      medications for PTSD are antidepressants, with two selective serotonin reuptake
      inhibitors (sertraline and paroxetine) currently Food and Drug Administration
      indicated for PTSD. However, many patients do not have an adequate response to
      antidepressants, therefore, combinations with other antidepressants or with other
      classes of psychotropic medication are often utilized to enhance the therapeutic
      response. Other agents that have been used include mood stabilizers, anti
      adrenergics, anxiolytics, and atypical antipsychotics. The heterogeneity of
      symptom clusters in PTSD as well as the complex psychiatric comorbidities (eg,
      with depression or substance abuse) further support the notion that combinations
      of medications may be needed. To date, there is a paucity of data to support
      specific strategies for augmenting antidepressants in PTSD. This review will
      address representative existing studies and discuss several potential
      pharmacologic strategies for patients suffering from treatment-refractory PTSD.

PMID- 15448586
TI  - Cognitive deficits following coronary artery bypass grafting: prevalence,
      prognosis, and therapeutic strategies.
AB  - There is increasing recognition that coronary artery bypass grafting (CABG) may
      be a risk factor for subtle cognitive decline although the presence and pattern
      of such decline has varied across studies. Cognitive deficits may present as
      short-term memory loss, executive dysfunction and psychomotor slowing. Although
      they are usually are not severe enough to meet criteria for mild cognitive
      impairment or vascular dementia, they lower quality of life and add to
      hospitalization and out-of-hospital costs. Proposed mechanisms include surgical
      related trauma, genetic susceptibility (eg, apolipoprotein E4 allele),
      microembolization, other vascular or ischemic changes, and temperature during
      surgery. Depression and anxiety levels predict subjective perception of these
      deficits more than objective cognitive performance. Both nonpharmacologic (eg,
      emboli reduction, temperature, or glucose management) and pharmacologic (eg,
      dexanabinol, glypromate, nootropics) strategies to prevent post-CABG cognitive
      deficits are under investigation. Given the large numbers of subjects who may
      already have CABG associated cognitive deficits, clinical trials of agents being
      tested for Alzheimer's disease (eg, donepezil, rivastigmine, memantine,
      neramexane, ginkgo) may also be informative. The results of multicenter long-term
      outcome studies (with matched control groups) as well as ongoing treatment trials
      will more conclusively address some of these issues. These data emphasize the
      need for clinicians to monitor cognitive function before and after coronary
      bypass surgery, and to educate patients.

PMID- 15448587
TI  - Differential expression of the human mu opiate receptor from different primary
      vascular endothelial cells.
AB  - BACKGROUND: Studies from our laboratory have identified a novel mu opiate
      receptor, mu3, which is expressed in several tissues, such as human vascular
      endothelial cells, leukocytes and invertebrate neural tissues. This novel mu
      receptor has been shown to be selective for opiate alkaloids, insensitive to
      opioid peptides, and also is coupled to constitutive nitric oxide release.
      MATERIAL/METHODS: In this study, we compare the mu3 receptor gene expression from
      three different vascular endothelial primary cell lines at the molecular level
      using a Taqman probe for the mu opiate receptor. RESULTS: Results from this study
      demonstrate that human umbilical vein endothelial cells (2.0, relative gene
      expression) and human pulmonary artery endothelial cells (1.1, relative gene
      expression) expressed more of the mu opiate receptor as compared to human
      arteriole endothelial cells (0.82, relative gene expression). CONCLUSIONS: The
      individual variations in mu receptor expression in these vascular tissues may
      explain the large variance in graft survival using saphenous veins for coronary
      artery bypass surgery.

PMID- 15448588
TI  - Near-infrared spectroscopic analysis of hepatic hemodynamics and oxygen
      metabolism after extensive hepatectomy.
AB  - BACKGROUND: Although major or extended hepatectomy may result in drastic
      alterations in the hemodynamics and oxygen metabolism of the residual livers,
      this issue remains to be elucidated in detail. MATERIAL/METHODS: In this study,
      in vivo near-infrared spectroscopy (NIRs) was performed to determine oxy-/deoxy
      hemoglobin (Hb) and oxidized/reduced cytochrome oxidase (Cyt.aa3) contents in
      hepatic tissues in a rat 70% hepatectomy model. We also investigated the
      effectiveness of Pringle occlusion for minimizing bleeding and the therapeutic
      effects of prostaglandin E1 (PGE1) on haemodynamics alteration after hepatectomy.
      RESULTS: After 70% hepatectomy, total Hb (oxy-Hb + deoxy-Hb) content was
      persistently elevated in the residual hepatic tissues, indicating congestion
      probably caused by surplus portal inflow. Oxidized Cyt.aa3 contents were elevated
      after hepatectomy, whereas reduced Cyt.aa3 contents were not significantly
      altered, indicating that mitochondrial respiration was not impaired. Pringle
      occlusion before hepatectomy per se did not cause deterioration of the
      hemodynamics or oxygen metabolism of the residual livers. The congestion of the
      residual liver after 70% hepatectomy was significantly improved by continuous
      injection of PGE1 (1.0 mg/kg/min) via the portal vein. CONCLUSIONS: The
      alteration of hemodynamics and oxygen metabolism in the liver after extended
      hepatectomy has been quantitatively evaluated using the NIRs.

PMID- 15448589
TI  - T cell-specific immune response induced by bacterial ghosts.
AB  - BACKGROUND: Bacterial ghosts, genetically inactivated Gram-negative bacterial
      pathogens, possess significant advantages over commonly used vaccination
      technologies. The autolysis of the bacteria, by the expression of a cloned viral
      gene, results in empty bacterial envelopes through the expulsion of cytoplasmic
      content. Immunostimulatory properties are generally presented through the
      targeting of professional antigen-presenting cells (APCs), such as macrophages
      and dendritic cells (DCs). MATERIAL/METHODS: This study investigated the
      interactions between porcine antigen-presenting cells and bacterial ghosts
      derived from the bacterial pathogen Actinobacillus pleuropneumoniae. The
      maturation process of DCs and their generation of immune responses to bacterial
      ghosts was shown by the expression of activation markers on their surface, as
      well as in the functional tests. RESULTS: A population of porcine APCs was
      generated from PBS by incubation with rpo-GMCSF and rh-IL-4. The cells expressed
      SWC3, MIL-2, CD80/86 molecules, as well as a high level of MSA3 molecules. The
      internalization of bacterial ghosts by the cells resulted in increased expression
      of MSA3 molecules. The capacity of T cells to proliferate when induced by
      bacterial ghosts was 4 times higher in the cultures including APCs than in
      cultures stimulated with bacterial ghosts only. CONCLUSIONS: We found that
      antigen-presenting cells have the capacity to stimulate specific T cells after
      the internalization and processing of Actinobacillus ghosts, as demonstrated by a
      strong specific T-cell response generated against the ghost antigens.

PMID- 15448590
TI  - High-affinity IgG to a major A. fumigatus allergen, Asp f 2, retards allergic
      response.
AB  - BACKGROUND: Allergic diseases represent a major health threat to humans. Allergen
      specific immunotherapy (SIT) is one of the significant approaches to the
      treatment of IgE-mediated allergy and its control. The mechanisms involved in SIT
      induced responses are complex and still speculative. Immunological events
      associated with successful SIT include an increase in allergen-specific
      "blocking" IgG, reduction in cytokine production, and induction of regulatory or
      suppressor cells. The aim of this study was to estimate the effect of SIT using a
      single major allergen of A. fumigatus, Asp f 2, or its dominant B-cell epitope,
      aa254-268, in a murine model of allergic aspergillosis. It is known that A.
      fumigatus (Af), a ubiquitous fungus, is implicated in the pathogenesis of a
      number of clinically different allergic diseases. MATERIAL/METHODS: BALB/c and
      C57BL/6 mice were immunized with Asp f 2, its proteolytic fragments or the
      recombinant peptide aa254-268 to induce high-affinity IgG to Asp f 2. Allergy to
      Af was induced by subcutaneous and intranasal immunization of previously SIT
      treated animals with an Af crude extract. RESULTS: The results of immunological
      and lung histological studies demonstrate a simultaneous increase in Asp f 2
      specific IgG and amelioration of allergic inflammatory symptoms in mice immunized
      with Asp f 2 or its peptides before exposure to Af crude allergen. CONCLUSIONS:
      Thus it was shown that the induction of IgG specific to major allergens or even
      to their B-cell epitopes induces protection from allergy provoked by natural
      allergens.

PMID- 15448591
TI  - Influence of preischemic short-term triiodothyronine administration on
      hemodynamic function and metabolism of reperfused isolated rat heart.
AB  - BACKGROUND: The "euthyroid sick syndrome" may intensify dysfunction of the heart
      during acute myocardial ischemia. The present research was undertaken to outline
      the effects of preischemic short-term triiodothyronine (T3) administration on
      hemodynamic function and metabolism of the myocardium during reperfusion.
      MATERIAL/METHODS: Thirty-six isolated working rat hearts were assigned to three
      experimental groups and a control group. The hearts were removed from the animals
      and perfused in the modified Langendorff model. They were subjected to 30 minutes
      of initial perfusion, 40 minutes of ischemia, and 15 minutes of reperfusion. The
      experimental groups received 10 extra minutes of T3 administration followed by
      initial perfusion (concentration of T3 was: group 1-5.4 pmol/l, group 2-27
      pmol/l, and group 3-54 pmol/l). Control hearts received perfusate without T3. We
      evaluated the postischemic recovery of left ventricular function (aortic
      pressures, heart rate, cardiac output), coronary flow, and oxygen consumption.
      RESULTS: Progressive percentage of recovery of aortic systolic pressure, aortic
      mean pressure, and cardiac output with increasing concentration of T3 was
      observed. Cardiac output reached the best recovery in the group with the highest
      concentration of T3 (80.9+/-7.5%) and was significantly better in comparison with
      the control group and the other experimental groups. No significant differences
      in coronary flow and oxygen consumption were noted. CONCLUSIONS: Triiodothyronine
      administered before ischemia improves postischemic left ventricular function with
      no changes in oxygen consumption and coronary flow.

PMID- 15448592
TI  - Enhancement of insulin signaling through inhibition of tissue lipid accumulation
      by activation of peroxisome proliferator-activated receptor (PPAR) alpha in obese
      mice.
AB  - BACKGROUND: The aim of the present study was to investigate the effect of
      PPARalpha activation on insulin signaling and lipid accumulation in the liver and
      skeletal muscle of insulin-resistant (ob/ob) mice. MATERIAL/METHODS: A known
      subtype-selective PPARalpha agonist, Wy-14,643, was administered to lean and
      ob/ob mice at 30 mg/kg/day for 4 weeks. Insulin (100 units/kg) or saline was
      injected into the portal vein of anesthetized mice. The liver and skeletal
      muscles were used for the detection of tyrosine phosphorylation of the insulin
      receptor (IR) and insulin receptor substrates (IRSs), as well as for the
      determination of both IRS-associated PI3-K activity and lipid content; in
      addition, the measurement of mRNA levels of PPAR-regulated genes was carried out.
      RESULTS: The PPARalpha agonist lowered plasma levels of glucose, insulin,
      triglycerides, and free fatty acids in ob/ob mice. Several PPARalpha-upregulated
      genes related to the transport and oxidation of fatty acids in the liver were
      increased by treatment with the agonist. The PPARalpha agonist significantly
      increased IR- and IRS-tyrosine phosphorylation and IRS-associated PI3-K activity
      in the liver and muscle of ob/ob mice, without exerting the same effects in lean
      mice. Moreover, these effects in ob/ob mice were accompanied by decreased
      triglyceride and fatty acyl-CoA contents in the liver and skeletal muscle.
      CONCLUSIONS: The present results suggest that inhibition of lipid accumulation by
      hepatic PPARalpha activation leads to an improvement in impaired insulin
      signaling in muscle tissue as well as in the liver of insulin-resistant mice.

PMID- 15448593
TI  - Asymptomatic atherosclerosis and myocardial infarction: risk modified by ability
      to adapt to stressful situations. Results from prospective cohort study "Men born
      in 1914", Malmo, Sweden.
AB  - BACKGROUND: The purpose of this study was to investigate whether different
      behaviors in a stressful situation modify the risk of atherosclerosis in
      association with a myocardial infarction, cardiovascular mortality, and all-cause
      mortality. Many individuals have atherosclerotic changes in their arteries but
      may never experience any symptoms nor develop cardiovascular disease. A
      myocardial infarction is caused by a disruption of a vulnerable atherosclerotic
      plaque. The mechanisms that trigger these events are not fully understood, but
      among the proposed agents is psychological stress. A differential in risk
      exposure could be expected since individuals differ in their ability to cope with
      stressful situations. MATERIAL/METHODS: In the prospective cohort study "Men born
      in 1914", atherosclerosis was noninvasively studied in the peripheral, carotid,
      and coronary arteries at a baseline examination in 1982/83. The serial Color Word
      Test, which is a semi-experimental way to assess how individuals adapt in a
      stressful situation, was administered at the same examination. Participants were
      followed-up regarding incidence of myocardial infarction and mortality until
      December 31 1996. RESULTS: Atherosclerosis was associated with an increased risk
      of myocardial infarction (relative risk (RR) 2.96; 95% confidence interval (CI)
      1.52 to 5.74) and cardiovascular mortality (RR 3.31; 95% CI 2.08 to 5.28) during
      follow-up only among the men who showed maladaptive behavior. No excess risk
      could be established in men with an adaptive behavior pattern. CONCLUSIONS: The
      serial Color Word Test can assist in identifying men at high cardiovascular risk.

PMID- 15448594
TI  - Abnormal eicosanoid pattern by blood leukocytes in gastroduodenal ulcer.
AB  - BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are implicated in
      several diseases showing altered tissue and leukocyte eicosanoid patterns, such
      as nasal polyposis and asthma. NSAIDs are also associated with gastrointestinal
      lesions, but it is unknown whether there is an altered eicosanoid pattern.
      MATERIAL/METHODS: The ex vivo modulated syntheses of prostaglandin E2 (PGE2) and
      peptido-leukotrienes (pLT) by leukocytes from 41 patients with gastroduodenal
      ulcer were compared with those of 61 healthy controls. Samples were incubated
      with diluent, arachidonic acid, or acetylsalicylic acid. The individual syntheses
      of PGE2 and pLT were quantified using competitive enzyme-immuno-assays followed
      by calculation of individual eicosanoid patterns. RESULTS: Controls synthesized
      approximately 4.9-fold whereas patients only approximately 2.9-fold more PGE2
      than pLT due to higher basal synthesis of pLT (67 and 125 pg/ml, respectively).
      The baseline PGE2/pLT ratio was slightly higher in patients (6.1) than in
      controls (5.7). The arachidonic acid-induced PGE2/pLT ratio in patients (14.2)
      was significantly higher than in controls (3.3). The acetylsalicylic acid-induced
      PGE2/pLT ratio in patients (3.5) was significantly lower than in controls (8.3)
      due to diminished PGE2 and elevated pLT. Integrated individual PGE2 and pLT
      values revealed a highly significantly altered eicosanoid pattern score in
      approximately 95% patients and approximately 12% controls. CONCLUSIONS: There is
      strong evidence of an altered eicosanoid pattern generated by leukocytes of
      gastroduodenal ulcer patients, which became obvious upon in vitro modulation by
      arachidonic or acetylsalicylic acid. The phenomenon of an abnormal eicosanoid
      pattern in gastroduodenal ulcer is yet not fully understood, but may have
      implications in pathophysiology and diagnostics.

PMID- 15448595
TI  - The sciatic nerve block in emergency settings: a comparison between a new
      anterior and the classic lateral approaches.
AB  - BACKGROUND: Anterior and lateral approaches to the sciatic nerve block are
      performed with the patient in the supine position. This could be an important
      advantage when mobilization to the limb involved is limited or painful,
      particularly in emergency conditions. The aim of this prospective, randomized
      study was to compare these two sciatic nerve blockades performed in an emergency
      setting. MATERIAL/METHODS: 59 patients undergoing post-traumatic lower extremity
      surgery under a sciatic nerve block were randomly assigned to either a lateral or
      an anterior approach. After appropriate positioning of the 150-mm insulated
      needle using a nerve stimulator, 25 ml of ropivacaine 0.75% were injected. Time
      to perform the block, sciatic nerve depth, success rate, and patient's comfort
      were analyzed. RESULTS: The mean time to perform the block was 4.9+/-4.0 min in
      the anterior group and 6.1+/-6.9 min in the lateral group (NS). The mean depth of
      sciatic nerve localization was 107+/-17 mm in the anterior group and 91+/-20 mm
      in the lateral group (P<0.05). Although the success was similar in both group
      (77% in the anterior group vs 79% in the lateral group), the number of technical
      failure (sciatic nerve stimulation impossible) was higher with the anterior
      approach (86% vs 33%; p<0.05). CONCLUSIONS: These data suggest that both
      techniques are of similar value in an emergency setting.

PMID- 15448596
TI  - Opposite effect of acute aerobic exercise on plasma endothelin levels in trained
      and untrained men.
AB  - BACKGROUND: Endothelin, a natural peptide exhibiting potent vasoconstrictor
      activity, may play a crucial role in cardiovascular disease. The purpose of the
      present study was to compare the effect of an aerobic exercise bout on plasma ET
      levels in trained and untrained subjects. MATERIAL/METHODS: Nine healthy
      physically active males and nine sedentary controls cycled at 60% of their
      maximal aerobic power for 30 min. Plasma endothelin was determined by enzyme
      immunoassay at rest and 30 min after the end of the exercise. Endothelin values
      were compared through two-way (training status x time) analysis of variance with
      repeated measures on time. Changes in plasma volume, calculated from hematocrit
      and hemoglobin data, were compared through independent Student's t test. RESULTS:
      We found a significant interaction of training status and time (p=0.05) resulting
      from opposite changes in the trained and untrained group (decrease in the former
      from 4.3+/-1.1 to 2.0+/-0.6 pg/ml vs. increase in the latter from 2.6+/-0.6 to
      3.3+/-1.1 pg/ml). Changes in plasma volume with exercise were significantly
      different (decrease in the trained group vs. increase in the untrained group,
      p=0.03). CONCLUSIONS: Our data indicate that aerobic training may reverse the
      augmentative effect of acute exercise on plasma endothelin levels. This
      adaptation may represent a novel beneficial effect of regular physical activity
      on human health.

PMID- 15448597
TI  - Electric activity of the gut in ulcerative colitis and Crohn's disease:
      electromyography as a tool for differentiating between the two conditions in the
      early stage.
AB  - BACKGROUND: The clinical diagnosis of ulcerative colitis (UC) and Crohn's disease
      (CD) may overlap and a diagnosis of intermediate colitis is made. We investigated
      the hypothesis that a difference in the electric pattern of the gut exists
      between UC and CD which may assist in the differentiation between the 2
      conditions in the early stage. MATERIAL/METHODS: The study comprised 16 patients
      with CD, 18 with UC, and 10 control subjects. It was performed during a scheduled
      laparotomy. The electric activity was recorded using 3 monopolar electrodes
      applied to the diseased colonic segments and to the corresponding segments in the
      control subjects. RESULTS: Regular slow waves (SWs) were recorded in control
      subjects. They showed the same frequency, amplitude, and conduction velocity from
      the 3 electrodes of the individual subjects. The SWs were followed or
      superimposed by action potentials (APs). In CD, edematous segments recorded SWs
      having wave variables lower than those of the controls; APs were less frequent.
      No SWs were registered from scarred gut segments. In UC, SWs had a higher
      frequency but lower amplitude and conduction velocity than those of control
      subjects; APs were more frequent. CONCLUSIONS: Electrocolography is suggested to
      act as an investigative tool in differentiating between UC and CD. The electric
      activity presented with a "tachyrhythmic" electrogram in UC and "bradyrhythmic"
      or "silent" electrogram in CD.

PMID- 15448598
TI  - Long-term survival in primary breast cancer: correlation with estrogen and
      progesterone receptor assay results and adjuvant tamoxifen therapy.
AB  - BACKGROUND: The presence of sex steroid receptors in breast cancer tissue is of
      considerable diagnostic/prognostic value. However, the relative utility of the
      diverse assays used for receptor detection/quantitation is disputed. We compared
      the utility of a monoclonal antibody-based semiquantitative immunohistochemical
      assay of estrogen receptor alpha (irERalpha) and of quantitative single-point
      radioligand assays of "cytosolic" estrogen (ERc) and progesterone receptors
      (PRc). MATERIAL/METHODS: Correlations were studied between the receptor levels in
      235 breast cancers in patients treated between 1987 and 1990. Relationships were
      then analyzed between tumor receptor status, overall survival (OS; end-point: 10
      years postmastectomy), age, axillary nodal status, and adjuvant tamoxifen in
      primary breast cancer patients for whom the respective data were accessible (N <
      or =121). RESULTS: Univariate analysis showed no correlation between OS and the
      ERc status, whereas positive irERalpha status was a favorable (p<0.05)
      prognosticator for the 5-year follow-up, and positive PRc status for the 10-year
      follow-up. Lymph node-positive patients who received adjuvant tamoxifen (2 x 10
      mg/day) for a minimum of 12 months had significantly longer OS than those who did
      not receive the treatment. Multivariate regression of Cox proportional risk
      showed significance of axillary metastases, adjuvant tamoxifen, and ER status,
      but not of age and PRc status as independent prognosticators of OS. CONCLUSIONS:
      These results show the prognostic utility of the PRc radioligand assay, a slight
      prognostic advantage of the irERalpha assay over the radioligand ERc assay, and
      stress the importance of adjuvant antiestrogen therapy for overall survival in
      node-positive primary breast cancer patients.

PMID- 15448599
TI  - Laparoscopic detection of sentinel lymph nodes using blue dye in women with
      cervical and endometrial cancer.
AB  - BACKGROUND: One of the cornerstones of gynecologic cancer surgery is the
      assessment and removal of the regional lymph nodes (LNs). Vital blue dye was used
      to shown the feasibility and accuracy of laparoscopic intraoperative lymphatic
      mapping of the sentinel lymph nodes (SNs) in patients with cervical and
      endometrial cancer (EC). MATERIAL/METHODS: Thirty-two women were submitted to
      laparoscopic staging of cervical and endometrial cancer. Patent blue dye (BPD)
      was intraoperatively injected into the cervix in 6 cases with stage I and one
      case with stage II cervical cancer. In 25 cases of stage I EC, the BPD was
      intraoperatively injected into the cervix and uterine fundus. After the BPD
      procedure, the patients underwent pelvic lymphadenectomy or para-aortic lymph
      node dissection and either laparoscopically assisted vaginal hysterectomy (26
      patients) or laparoscopic radical hysterectomy (5 patients). RESULTS:
      Laparoscopically assisted surgical staging was successfully performed in all
      cases. SN detection was successful in 100% of 7 women with cervical cancer. In
      one patient with advanced cervical cancer the metastatic SN was found. A
      deposition of dye into at least one lymph node was found in 21 out of 25 cases
      (84%) in women with EC. Uptake of the BPD was observed in a total of 53 (14.4%)
      of 367 LNs. Histological analysis of two LNs of the 53 were positive for
      metastases, whereas the remaining 51 were negative. CONCLUSIONS: With the use of
      laparoscopy, accurate detection using blue dye on sentinel lymph nodes in uterine
      cancer is feasible technique.

PMID- 15448600
TI  - Case report of tuberculous panophthalmitis.
AB  - BACKGROUND: Although tuberculosis is very common in the Indian sub-continent,
      tuberculous panophthalmitis has not been reported from this region so far. We
      report a case of a young girl with tuberculous panophthalmitis. CASE REPORT: A 12
      year-old female child presented with painless progressive loss of vision in the
      right eye of two months' duration. Examination revealed diffuse corneal haze with
      deep vascularization, iris nodules, and scleral necrosis. Histopathological
      examination of the enucleated eye revealed necrotizing granulomatous
      inflammation, multiple epitheloid cell granulomas, and Langhan's giant cells,
      along with large areas of caseous necrosis. Chest X-ray revealed right hilar
      lymphadenopathy with right lower zone infiltration and a small pleural effusion.
      Considering the clinical picture, histopathology and chest findings, a diagnosis
      of disseminated tuberculosis was made, and standard four-drug anti tubercular
      treatment was started. At 2 months follow up there was radiological resolution of
      the lung lesions and pleural effusion. CONCLUSIONS: Clinical features suggestive
      of tubercular panophthalmitis are absence of pain, presence of nodules on or
      within the eyeball, and spontaneous perforation. We would like to emphasize that
      in all susceptible individuals presenting with clinical suspicion of ocular
      tuberculosis it would be prudent to start early anti-tubercular therapy to
      prevent progression to panophthalmitis. A complete systemic workup to look for
      any other possible focus of tubercular involvement must be done.

PMID- 15448601
TI  - Mycobacterium abscessus as a cause of pacemaker infection.
AB  - BACKGROUND: Mycobacterial infections of a pacemaker insertion site are very rare
      clinical events. Such infections are caused primarily by staphylococci and
      streptococci and, less frequently, Gram-negative organisms. CASE REPORT: We
      describe a case of pacemaker infection caused by Mycobacterium abscessus which
      is, to our knowledge, only the second such case described in the literature. The
      patient responded well to removal of the pacemaker wire and treatment with six
      months of clarithromycin. CONCLUSIONS: Mycobacteria have been very infrequently
      reported as causes of pacemaker infections. To our knowledge, only one case of
      such infection caused by M. abscessus has been described in the literature.
      Herein we present the second case of a patient with pacemaker infection caused by
      Mycobacterium abscessus. This case underscores the importance of considering
      atypical mycobacteria in pacemaker infections, particularly if the Gram stain or
      the standard cultures are negative. Removal of the contaminated foreign body
      seems to be an integral part of successful management.

PMID- 15448602
TI  - Atlantoaxial instability and myelopathy due to an ossiculum terminale persistens.
AB  - BACKGROUND: Many cases of ossiculum terminale in Down's syndrome have been
      reported. We describe an unusual case of sudden atlantoaxial instability in a
      previously healthy woman without a history of trauma due to a dystopic ossiculum
      of the dens that could be classified as an ossiculum terminale persistens or as
      os odontoideum according to different classification proposals. CASE REPORT: A 36
      year-old woman was admitted with neck pain and Lhermitte's sign. Neurological
      examination revealed spasticity of both upper and lower limbs. Radiological
      evaluation of the cervical spine showed an ossiculum close to the anterior arch
      of the atlas. Flexion and extension films revealed an atlantoaxial instability.
      Additional findings using computerized tomography and magnetic resonance Imaging
      provided significant information about the soft tissue structures. The patient
      underwent a C1-C2 posterior cervical wiring and interspinous fusion with the
      Sonntag technique. Postoperatively, the patient was neurologically intact and
      without any symptoms. CONCLUSIONS: In the present report we address the notion
      that, in cases of atlantoaxial instability and myelopathy due to a dens anomaly,
      surgical intervention is required and that there is no need to distinguish which
      type of anomaly really exists according to different classification schemes.

PMID- 15448603
TI  - Drotrecogin alfa (activated) in severe sepsis.

PMID- 15448605
TI  - Comment to: Music alters constitutely expressed opiate and cytokine processes in
      listeners; Med Sci Monit, 2004; 10(6): MS18-27.

PMID- 15448607
TI  - Comment to: Protective effects of green tea catechins on cerebral ischemic
      damage; Med Sci Monit, 2004; 10(6): BR166-74.

PMID- 15448608
TI  - Comparison between auto-cross-correlation coefficients and coherence methods
      applied to the EEG for diagnostic purposes.
AB  - BACKGROUND: Power-spectrum and coherence analysis of the EEG has often been
      applied in the study of various forms of brain dysfunction. The examination of
      differences in intra-hemispheric coherence and a novel method based on auto-cross
      correlation algorithms between the left and right hemispheres of the same EEG are
      investigated in this paper. MATERIAL/METHODS: Both coherence and the proposed
      method are computed from the same EEG segment across the EEG spectrum (0-64 Hz).
      In this experiment, five EEGs of different patients with severe brain damage were
      used. The novelty of this study lies in the fact that the autocorrelation
      coefficients are extracted in a particular spectrum, in contrast to the
      traditional coherence method, which is based on a measure of the square of the
      linear association between the two EEG signals from the entire EEG spectrum.
      RESULTS: The results of the application of coherence and the proposed method
      showed that particular pairs of symmetrical cortex channels differed dramatically
      in specific damaged areas. CONCLUSIONS: Statistical analysis of the above results
      showed that the proposed method is more accurate than coherence because it could
      recognize the cases of the patients to a significant statistical degree, whereas
      the coherence method showed weakness in recognizing them.

PMID- 15448609
TI  - Craniocervical artery dissection: diagnosis and follow-up with MR imaging and MR
      angiography.
AB  - BACKGROUND: Our aim was to determine the value of MR angiography (MRA) in
      combination with MRI in the diagnosis and follow-up of craniocervical artery
      dissections (CCAD) and to document the effectiveness of conservative medical
      treatment in these patients. MATERIAL/METHODS: In seven patients, six internal
      carotid artery dissections and two vertebrobasilar artery dissections were
      studied with 2D and 3D TOF MRA and fat-saturated T1W images. MRA projection
      images, source images, and T1W images with fat saturation were evaluated for the
      presence or absence of criteria for dissection. RESULTS: MRA projection images
      showed narrowing and/or occlusion of lumen in all patients. Dissection flap was
      identified in 5 of the 8 dissections. Both MRA source images and T1W images with
      fat saturation were useful in showing the increased external diameter of the
      dissected vessel and the mural hematoma; although the latter proved to give
      better results. Almost complete resorption of hematoma and normalization of flow
      were achieved between 1.5 to 7 months. CONCLUSIONS: This study further supports
      the approach that MRA accompanied by T1W images with fat saturation should be the
      method of choice in the diagnosis and follow-up of CCAD. Fat-suppressed T1W
      images improve detection of the mural hematoma, especially in the late sub-acute
      phase and during follow-up. Conservative medical treatment may be effective,
      obviating the need for aggressive treatment options.

PMID- 15448610
TI  - Chemopreventive effect of M2000, a new anti-inflammatory agent.
AB  - BACKGROUND: An emerging body of literature has recently defined a reduced risk of
      cancer following the use of nonsteroidal anti-inflammatory drugs (NSAIDs), which
      are generally able to exert an apoptotic property and inhibitory effects on the
      activity and/or expression of matrix metalloproteinases (MMPs). This study was
      undertaken to explore the role of a newly designed NSAID, M2000 (C6H10O7), as an
      anti-inflammatory drug in chemoprevention therapy under in vitro conditions.
      MATERIAL/METHODS: The influence of M2000 on a fibrosarcoma cell line (WEHI-164)
      was investigated using an in vitro cytotoxicity assay, terminal
      deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay to
      assess apoptosis, and gelatin zymography for evaluating the activity of matrix
      metalloproteinase 2 (MMP-2). RESULTS: Cytotoxicity analysis of M2000 showed a
      much higher tolerability than the other tested drugs (diclofenac, piroxicam, and
      dexamethasone) in that it showed no cytotoxic effect compared with them. The dose
      dependent inhibitory effect of M2000 at concentrations of 20, 40, 80, and 200
      microg/ml was significantly greater than that of dexamethasone and of piroxicam
      at a concentration of 200 microg/ml, whereas the inhibitory activity of M2000
      paralleled diclofenac at doses of 10, 20, 40, and 200 microg/ml. Moreover, the
      apoptotic efficacy of M2000 was similar to that of dexamethasone. CONCLUSIONS:
      Based on our data, the induction of apoptosis together with MMP-2 inhibition
      could be indicative of a chemopreventive property of M2000. Thus this novel NSAID
      might be considered as a chemopreventive drug in the potential prevention and
      treatment of cancer and in inhibition of the angiopathogenic process.

PMID- 15448611
TI  - Intrathecal labor analgesia using levobupivacaine 2.5 mg with fentanyl 25 microg-
      would half the dose suffice?
AB  - BACKGROUND: This randomized, double-blinded, controlled trial of 40 patients in
      early labor was conducted to determine whether a reduction in the total amount of
      intrathecal levobupivacaine and fentanyl would reduce the incidence of motor
      blockade and pruritus, respectively. MATERIAL/METHODS: Combined spinal epidural
      (CSE) analgesia was instituted. Group A (n=20) received 2.5 mg levobupivacaine
      with 25 microg fentanyl intrathecally while group B (n=20) received half that
      dose. RESULTS: The duration and quality of spinal analgesia were comparable in
      the 2 groups. There was a reduced incidence of motor blockade in patients from
      Group B (P<0.01). This was apparent 5 minutes after the spinal injection and
      persisted throughout the next 30 minutes. However, there were also 2 parturients
      from this group who required epidural supplementation as a result of partial
      analgesia. Other side effects were not different between the 2 groups.
      CONCLUSIONS: A reduction in the intrathecal dose of 2.5 mg levobupivacaine with
      25 microg fentanyl by half is an option for CSE in labor because it can reduce
      the incidence of motor impairment. Although the reduced dose does not differ
      significantly from the full dose with respect to onset, duration, and quality of
      analgesia for the majority of parturients, it must be highlighted that
      insufficient labor analgesia may occur in certain individuals. In this respect,
      further studies related to dosage of intrathecal levobupivacaine in obstetric
      labor analgesia will be beneficial in substantiating this point.

PMID- 15448612
TI  - Improvement in clinical course and laryngeal appearance in selected patients with
      chronic laryngitis after eight weeks of therapy with rabeprazole.
AB  - BACKGROUND: One well-known extraesophageal manifestation of gastroesophageal
      reflux disease (GERD) is chronic laryngitis. The aim of this study was to
      estimate the efficiency of eight weeks of treatment with the PPI rabeprazole in a
      selected group of patients with chronic idiopathic laryngitis without typical
      GERD symptoms. MATERIAL/METHODS: Seventeen patients (nine men and eight women)
      aged 35-72 years, with long histories (0.5 to 6 years) of chronic idiopathic
      laryngitis were included in the study. Larynx appearance was estimated by
      laryngostroboscopy. This examination, as well as interview and physical
      examination were performed in all patients at the start of the study and after 8
      weeks of treatment with 20 mg rabeprazole taken orally twice a day. RESULTS:
      There was remarkably good therapeutic outcome, clinical symptoms such as
      hoarseness and pharyngeal pain resolved, respectively, in 68.7 and 78.5% of
      patients and laryngeal signs in 50-80%, except for weak tension of the vocal
      cords which was observed in 12 patients at the start and end of the study.
      CONCLUSIONS: Treatment with a proton pump inhibitor can be considered as a first
      line diagnostic and therapeutic method in patients with idiopathic chronic
      laryngitis. Weak tension of vocal cords was often seen in these patients and
      persisted after the 8-week-long treatment.

PMID- 15448613
TI  - Selective potentiation of proximal processes: neurobiological mechanisms for
      spread of activation.
AB  - BACKGROUND: Signal detection by one sense selectively activates other relevant
      systems. For example, when an auditory stimulus comes from a specific location,
      visual sensitivity, tactile sensitivity, and motor readiness increase for stimuli
      or actions in that direction. This observed phenomenon provides an apparent
      sensory-sensory and sensory-motor coordination with evolutionary adaptive
      advantages. Anatomically, many of the relevant cortical sites are adjacent to
      each other. MATERIAL/METHODS: The spread of excitation from an active processing
      site in the cortex to nearby functions can be seen in brain scans. Cognitive and
      affective functions also selectively activate each other and are activated by
      focal sensory stimulation based on cortical proximity. These behavioral
      interactions seem to offer no selective adaptability but still call for a model
      of possible mediation. The objective of the current paper is to consider evidence
      for competing mechanisms for the flow of cortical activation that are
      characterized by being neurobiologically feasible, showing preferential
      activation over short distances, and having empirical support. RESULTS: These
      three criteria are met by blood flow, heat flow, nearest networks,
      electromagnetism, and inhibition. CONCLUSIONS: It is suggested that several of
      these mechanisms work independently or synergetically to produce the known
      interactions among attention, affect, cognition, and behavior. An understanding
      of these processes and the functional cerebral space in which they operate can
      suggest practical applications for the manipulation of behavior.

PMID- 15448614
TI  - PTEN regulatory functions in tumor suppression and cell biology.
AB  - PTEN is a dual-specificity phosphatase with both protein phosphatase and lipid
      phosphatase activity. PTEN is the first phosphatase identified as a tumor
      suppressor. Not since the discovery of p53 has a tumor suppressor generated such
      interest. Initial studies performed on cancer cell lines suggested that PTEN may
      be responsible for almost all types of cancer, both solid tumors and
      hematological malignancies. Biallelic deletion of PTEN has been associated with
      advanced stage tumors or metastatic disease. PTEN has been shown to play a
      pivotal role in apoptosis, cell cycle arrest, and possibly cell migration.
      Emerging data suggest that this may be an oversimplification of PTEN's role, and
      that PTEN may be haploinsufficient for tumor progression and may play important
      roles in other cellular functions such as angiogenesis and MAP kinase signaling.

PMID- 15448615
TI  - What are the pancreatic target cells for gastrin and its CCKB receptor? Is this a
      couple for cancerous cells?
AB  - The objectives of this review are to summarize, analyse and discuss the roles
      played by the CCK receptor subtypes and their agonists on pancreatic enzyme
      secretion, pancreas growth and regeneration, define the receptors specific target
      cells and evaluate the role of gastrin in pancreatic pathologies including
      cancer. In rodents, it is clear that the CCKARs present on pancreatic acinar
      cells play a major role in enzyme secretion. In large mammals, CCK does not seem
      to be the final mediator of enzyme release. In rat, gastrin and its CCKBR seem
      responsible for foetal pancreas growth while after birth, CCK was shown to be the
      most potent trophic factor via occupation of its CCKAR. In pig and human, no one
      has yet established a direct link between CCK, gastrin and pancreas growth. In
      rodent's pancreas, the CCKAR were observed on acinar cells as well as on islet's
      alpha and beta cells; in six other species, the CCKAR were present only on alpha
      and beta cells with the CCKBR always present on delta cells. The CCKBRs were
      overexpressed in acute pancreatitis and in metaplastic pancreas following duct
      ligation. In pancreatic cancer cells, a gastrin autocrine loop involving the
      CCKBR was suggested. The presence of both CCKR-subtypes and gastrin was observed
      in many pancreatic tumors; however, their role in cancer growth remains
      controversial.

PMID- 15448616
TI  - Induced abortion and traumatic stress: a preliminary comparison of American and
      Russian women.
AB  - BACKGROUND: Individual and situational risk factors associated with negative
      postabortion psychological sequelae have been identified, but the degree of
      posttraumatic stress reactions and the effects of culture are largely unknown.
      MATERIAL/METHODS: Retrospective data were collected using the Institute for
      Pregnancy Loss Questionnaire (IPLQ) and the Traumatic Stress Institute's (TSI)
      Belief Scale administered at health care facilities to 548 women (331 Russian and
      217 American) who had experienced one or more abortions, but no other pregnancy
      losses. RESULTS: Overall, the findings here indicated that American women were
      more negatively influenced by their abortion experiences than Russian women.
      While 65% of American women and 13.1% of Russian women experienced multiple
      symptoms of increased arousal, re-experiencing and avoidance associated with
      posttraumatic stress disorder (PTSD), 14.3% of American and 0.9% of Russian women
      met the full diagnostic criteria for PTSD. Russian women had significantly higher
      scores on the TSI Belief Scale than American women, indicating more disruption of
      cognitive schemas. In this sample, American women were considerably more likely
      to have experienced childhood and adult traumatic experiences than Russian women.
      Predictors of positive and negative outcomes associated with abortion differed
      across the two cultures. CONCLUSIONS: Posttraumatic stress reactions were found
      to be associated with abortion. Consistent with previous research, the data here
      suggest abortion can increase stress and decrease coping abilities, particularly
      for those women who have a history of adverse childhood events and prior
      traumata. Study limitations preclude drawing definitive conclusions, but the
      findings do suggest additional cross-cultural research is warranted.

PMID- 15448617
TI  - A novel connexin46 (GJA3) mutation in autosomal dominant congenital nuclear
      pulverulent cataract.
AB  - PURPOSE: To report the identification of a novel mutation of connexin46 in a
      large Chinese family with autosomal dominant congenital nuclear pulverulent
      cataract. METHODS: Genetic linkage analysis was performed on the known genetic
      loci for autosomal dominant congenital nuclear pulverulent cataract with a panel
      of polymorphic markers and mutations were screened by direct sequencing. RESULTS:
      Significant two point lod score was generated at marker D13S175 (Zmax=3.61,
      theta=0), further linkage and haplotype studies confined the disease locus to
      13q11-13. Mutation screening of connexin46 in this family revealed an A->C
      transition at position 563 (N188T) of the cDNA sequence, creating a novel AleI
      restriction site that co-segregated with affected members of the pedigree, but
      was not present in unaffected relatives or 100 normal individuals. CONCLUSIONS:
      Our finding expands the spectrum of connexin46 mutations causing autosomal
      dominant congenital nuclear pulverulent cataract, and confirms the role of
      connexin46 in the pathogenesis of autosomal dominant congenital nuclear
      pulverulent cataract.

PMID- 15448618
TI  - Differential expression of splice variants of chemokine CCL27 mRNA in lens,
      cornea, and retina of the normal mouse eye.
AB  - PURPOSE: Constitutive expression of RNA sequences complementary to the chemokine
      CCL27 mRNA has been found in the normal mouse eye. This study examines the nature
      and location of these endogenous RNAs in ocular tissues. METHODS: Conventional RT
      PCR, 5' RACE, and dideoxy DNA sequencing were used to examine the sequences of
      CCL27 related RNAs in the eye. Expression levels of specific RNAs were measured
      by real time PCR. Tissue distribution of RNA transcripts was determined by RT-PCR
      using RNA from microdissected tissues and by in situ hybridization with
      radiolabeled riboprobes. RESULTS: We detect 5 distinct splice variants derived
      from transcription of the CCL27 gene locus. The most abundant form codes for a
      non-secreted protein, PESKY, and is expressed in lens, cornea, and retina.
      Another variant corresponds to the mRNA of the secreted chemokine and is
      synthesized in the cornea, but not in retina or lens. The remaining splice
      variants are novel and may be eye specific, but have only short open reading
      frames (<50 amino acids). CCL27 transcripts are most abundantly expressed in the
      retina, as judged by in situ hybridization. CONCLUSIONS: PESKY and other CCL27
      splice variants of unknown function are widely expressed in ocular tissues.
      Analysis of CCL27 transcripts from lens, retina, and cornea indicates that mRNA
      for the secreted chemokine, CCL27, is endogenously expressed only in the cornea
      and may play a role in ocular immune responses involving CD4 lymphocytes in this
      tissue.

PMID- 15448619
TI  - The IXI/V motif in the C-terminal extension of alpha-crystallins: alternative
      interactions and oligomeric assemblies.
AB  - PURPOSE: Alpha-crystallin, a hetero-oligomer of alphaA- and alphaB-crystallin, is
      involved in maintaining eye lens transparency, primarily by its structural
      packing and chaperone activity. alphaA- and alphaB-crystallin share significant
      sequence homology, which is almost exclusively restricted to the central,
      conserved "alphaA-crystallin domain". The flanking N-terminal domain and C
      terminal extension are highly variable both in sequence and length. Mutations and
      age-related post-translational modifications of these proteins are associated
      with congenital and age-onset cataracts. Interestingly, most mutations or
      truncations in the C-terminal extensions of the alpha-crystallins and other alpha
      sHsps like Hsp27 lead to pathology. It is therefore important to understand the
      structure/function relationship of this region. Sequence alignment of the C
      terminal extensions of alphaA- and alphaB-crystallin with other homologues shows
      a conserved IXI/V motif. The purpose of this study was to investigate the role of
      this conserved motif, IPV in alphaA-crystallin and IPI in alphaB-crystallin
      (corresponding to residues 159-161 in both crystallins), in the structure and
      chaperone activity. METHODS: The isoleucine/valine residues in the IPV motif of
      alphaA-crystallin and the IPI motif of alphaB-crystallin were mutated to glycine
      and studied the secondary and tertiary structure of the mutant proteins using
      circular dichroism and fluorescence spectroscopy, and the quaternary structure
      using glycerol density gradient centrifugation and dynamic light scattering.
      Chaperone activity was studied at 37 degrees C and 25 degrees C using DTT induced
      aggregation of insulin as a model system. We have performed fluorescence
      resonance energy transfer (FRET) experiments to investigate the interactions of
      this motif in homo- and hetero-oligomers. Since alphaB-crystallin is devoid of
      Cys residues, we have introduced a Cys residue flanking the IPI motif
      (T162CalphaB-crystallin) to facilitate fluorescence labeling studies. RESULTS:
      Unlike in other homologues from plants or prokaryotes, mutation of the
      isoleucine/valine residues in alpha-crystallins does not result in oligomer
      dissociation or loss of chaperone activity. On the contrary, the mutant proteins
      retain their capacity to oligomerize and show enhanced chaperone activity at 37
      degrees C. The mutants also exhibit significantly higher chaperone-like activity
      at 25 degrees C. FRET experiments show that the region spanning the IPI/V motif
      comes in proximity either to the beta-strands of the "alpha-crystallin" domain or
      the corresponding IPI/V region of another subunit. CONCLUSIONS: Our mutational
      studies show that the IPI/V motif has a propensity to participate in inter
      subunit interactions, either with regions in the alpha-crystallin domain or with
      the corresponding IPI/V region on another monomer. These interactions are
      important in the structure and function of alpha-crystallins. This motif also
      appears to be important in the temperature dependent chaperone-like activity of
      the alpha-crystallins. The propensity of the IPI/V motif to form multiple inter
      subunit interactions may contribute to the diversity in structure and function
      seen in the alpha-crystallin/sHsp family.

PMID- 15448622
TI  - San Diego county wildfires: perspective of county officials.

PMID- 15448624
TI  - Perceptions of work in humanitarian assistance: interviews with returning Swedish
      health professionals.
AB  - Health personnel volunteering for humanitarian assistance assignments work in
      increasingly dangerous situations and increasingly complex roles. A qualitative
      analysis of interviews with returning Swedish aid workers, who collectively had
      been on 74 missions in 32 different countries, revealed that they felt positive
      about their contribution, but experienced high levels of stress and frustration.
      They were also surprised and inadequately prepared for tasks that fell outside
      their professional health care training, including ones demanding pedagogic and
      management skills. The volunteers perceived their success on humanitarian
      assistance assignments as being affected not only by their own professional
      competence and special preparatory training, but also by many other factors. In
      particular, recruiting organizations could improve volunteer performance by
      accepting only experienced professionals, requiring special preparatory training,
      clarifying the exact nature of the work, and providing better support during the
      assignment. Further analysis of humanitarian assistance as a complex and dynamic
      system involving multiple 'actors' could lead to improved understanding and
      better performance.

PMID- 15448626
TI  - Quick clinical note: emergency care includes prevention of influenza.

PMID- 15448625
TI  - Biological, chemical, and nuclear terrorism readiness: major concerns and
      preparedness of future nurses.
AB  - INTRODUCTION: The nursing profession is developing educational resources to
      improve their response to victims of nuclear, biological, and chemical terrorism.
      Future nurses may differ from practicing nurses in their perspective of what is
      critical information. The purpose of this study was to identify student nurses'
      major concerns in relation to working with victims of terrorism. METHOD: A
      descriptive study was used to identify how future nurses might practice as
      caregivers for victims of terrorism. The study population consisted of a
      convenience sample of 95 junior and senior baccalaureate nursing students at a
      mid-south state university. The students were given an anonymous questionnaire
      regarding their concerns and how their lives had changed after September 11,
      2001. The questionnaire consisted of 19 major items that identified demographics
      and perceptions and concerns regarding preparedness, willingness to work,
      expectation of future terrorism events, effect on lifestyle, and other fears
      related to terrorism or caring for victims of terrorism. A Cronbach alpha
      coefficient of reliability on standardized items was .745. RESULTS: Students'
      primary concern was for the safety of themselves and their families. They were
      primarily concerned about having adequate protection for all types of terrorist
      agents and indicated they would not be willing to care for victims if there was a
      lack of protection for both themselves and family. Although the nursing school
      faculty had provided self-education information about terrorism, students did not
      demonstrate an accurate understanding of the pathogenic nature of many agents.

PMID- 15448627
TI  - Pediatric emergency preparedness for mass gatherings and special events.

PMID- 15448638
TI  - Two billion years of actin. Meeting on cytoskeletal dynamics: from cell biology
      to developmental disease.

PMID- 15448637
TI  - Clathrin-mediated transport: assembly required. Workshop on Molecular Mechanisms
      of Vesicle Selectivity.

PMID- 15448639
TI  - SNM-dependent recombinational repair of oxidatively induced DNA damage in
      Arabidopsis thaliana.
AB  - Two different roles for SNM (sensitive to nitrogen mustard) proteins have already
      been described: the SNM1/PSO2-related proteins are involved in the repair of the
      interstrand crosslink (ICL) and the ARTEMIS proteins are involved in the V(D)J
      recombination process. Our study shows that an Arabidopsis SNM protein, although
      structurally closer to the SNM1/PSO2 members, shares some properties with ARTEMIS
      but also has novel characteristics. Arabidopsis plants defective for the
      expression of AtSNM1 did not show hypersensitivity to the ICL-forming agents but
      to the chemotherapeutic agent bleomycin and to H(2)O(2). AtSNM1 mutant plants are
      delayed in the repair of oxidative damage and did not show enhancement of the
      frequency of somatic homologous recombination on exposure to H(2)O(2) and to the
      bacterial elicitor flagellin, both inducing oxidative stress, as observed in the
      control plants. Therefore, our results suggest the existence, in plants, of a
      novel SNM-dependent recombinational repair process of oxidatively induced DNA
      damage.

PMID- 15448641
TI  - Accepting uncertainty.

PMID- 15448640
TI  - Epigenome changes in active and inactive polycomb-group-controlled regions.
AB  - The Polycomb group (PcG) of proteins conveys epigenetic inheritance of repressed
      transcriptional states. In Drosophila, the Polycomb repressive complex 1 (PRC1)
      maintains the silent state by inhibiting the transcription machinery and
      chromatin remodelling at core promoters. Using immunoprecipitation of in vivo
      formaldehyde-fixed chromatin in phenotypically diverse cultured cell lines, we
      have mapped PRC1 components, the histone methyl transferase (HMT) Enhancer of
      zeste (E(z)) and histone H3 modifications in active and inactive PcG-controlled
      regions. We show that PRC1 components are present in both cases, but at different
      levels. In particular, active target promoters are nearly devoid of E(z) and
      Polycomb. Moreover, repressed regions are trimethylated at lysines 9 and 27,
      suggesting that these histone modifications represent a mark for inactive PcG
      controlled regions. These PcG-specific repressive marks are maintained by the
      action of the E(z) HMT, an enzyme that has an important role not only in
      establishing but also in maintaining PcG repression.

PMID- 15448642
TI  - Understanding the jigsaw of evidence-based dentistry. 3. Implementation of
      research findings in clinical practice.
AB  - Part one of this three-part series provided an overview of evidence-based
      dentistry (EBD), provided one definition of EBD and, having introduced the EBD
      matrix, concentrated on the research synthesis part of the jigsaw puzzle. Part
      two focused on the middle row of this puzzle, the dissemination of research
      results. This final article deals with perhaps the most vital but the most often
      overlooked element of the puzzle: implementation of research findings in clinical
      practice.

PMID- 15448643
TI  - Does splint therapy work for temporomandibular pain?

PMID- 15448644
TI  - Local tetracycline is an effective adjunct in the treatment of chronic
      periodontitis.

PMID- 15448645
TI  - Evidence of downward trends in dental caries in Latin America and the Caribbean.

PMID- 15448646
TI  - Periodontal disease and cardiovascular disease.

PMID- 15448647
TI  - Common complications with implants and implant prostheses.

PMID- 15448648
TI  - Are bitewings of value in epidemiological studies of dental caries?

PMID- 15448649
TI  - Good short-term survival of IPS-Empress crowns.

PMID- 15448650
TI  - Functional appliances and mandibular growth--is there an effect?

PMID- 15448651
TI  - Orthodontic treatment has little to do with temporomandibular disorders.

PMID- 15448653
TI  - Distalising upper first permanent molars.

PMID- 15448652
TI  - Limited evidence supports use of oral appliances in obstructive sleep apnoea.

PMID- 15448654
TI  - Third molars may double the risk of an angle fracture of the mandible.

PMID- 15448655
TI  - Smokeless tobacco use is associated with a substantial risk of oral cancers in
      India.

PMID- 15448658
TI  - Clinical practice guidelines on emergency management of acute apical
      periodontitis and acute apical abscess. Evidence-based Dentistry 2004;5:7-11.

PMID- 15448660
TI  - Hyponatremia and syndrome of inappropriate antidiuretic hormone secretion
      complicating stem cell transplantation.
AB  - Hyponatremia is a common electrolyte disorder in hospitalized patients. Although
      there are a few case reports of hyponatremia following stem cell transplantation
      (SCT), no reports concerning the incidence are currently available. We describe
      the occurrence of hyponatremia and the syndrome of inappropriate secretion of
      antidiuretic hormone (SIADH) following SCT. In a single center analysis of 140
      patients, hyponatremia and SIADH were observed in 40 and 11.4% of patients,
      respectively, following SCT. Risk factors for SIADH included young age,
      transplantation from an HLA-mismatched or unrelated donor, cord blood
      transplantation, and graft-versus-host disease prophylaxis with methyl
      prednisolone. Multivariate analysis revealed that transplantation from an HLA
      mismatched donor and performance of SCT in a child below 4 years of age were risk
      factors for SIADH. For patients who underwent SCT from an HLA-mismatched or
      unrelated donor, those with SIADH showed a significantly higher overall survival
      rate (90.9 vs 40.2%) and event-free survival rate (77.8 vs 33.8%) compared to
      those without SIADH. Overall, our data show that hyponatremia and SIADH are
      relatively common complications following SCT, especially in children below 4
      years of age and after SCT from an HLA-mismatched donor.

PMID- 15448661
TI  - Second cord blood transplantation (CBT) with reduced-intensity conditioning for
      graft failure after the first CBT for AML.

PMID- 15448662
TI  - The molecular regulation of iron metabolism.
AB  - Mammalian iron homeostasis requires meticulous control of proteins involved in
      intestinal iron absorption and tissue iron management. Recent studies in animal
      models have provided important insights into iron physiology. This review
      describes our current understanding of the regulation of iron trafficking and its
      perturbation in genetic iron disorders.

PMID- 15448663
TI  - Iron overload and hematologic malignancies.
AB  - Although iron is essential for cell replication and survival, an increase of body
      iron stores has been implicated in the development of cancer. However, while the
      association between iron overload and hepatocellular carcinoma is well
      documented, the relationship with nonhepatocellular malignancies remains ill
      defined. In this review, we briefly report the present knowledge regarding the
      association between iron overload and hematologic malignancies.

PMID- 15448664
TI  - Efficacy of granulocyte and granulocyte-macrophage colony-stimulating factors in
      the induction treatment of adult acute lymphoblastic leukemia: a multicenter
      randomized study.
AB  - In all, 236 adults with newly diagnosed acute lymphoblastic leukemia (ALL) were
      randomly assigned to receive either granulocyte colony-stimulating factor (G
      CSF), or granulocyte-macrophage CSF (GM-CSF), or no CSF during a 4-week 4-drugs
      induction chemotherapy. Two successive trials were performed. CSFs were given
      from the last infusion of anthracycline in Trial 1 or from day 4 of induction
      therapy in Trial 2 until neutrophil recovery. A total of 95 patients were
      included in the G-CSF group, 67 in the GM-CSF group, and 74 in the control group.
      Overall, CSFs showed a trend for a reduced incidence of severe infections and of
      days with antibiotics. Median time for neutrophil recovery was 17 days with G
      CSF, 18 days with GM-CSF, and 21 days without CSF. In Trial 2, duration of
      hospitalization was significantly lower in the G-CSF group than in the other
      groups (P < 0.05). Time to neutrophil recovery was also significantly shorter (P
      < 0.05) and severe infections were lower in the G-CSF group (P = 0.01). CR rate
      was higher in the GM-CSF group as compared to the control group. This tended to
      be confirmed for the most aggressive ALL and was statistically significant for
      Philadelphia-positive ALL after salvage therapy (P = 0.04). There were no
      significant differences between the three groups in terms of disease-free
      survival.

PMID- 15448665
TI  - Nonmyeloablative stem cell transplantation in patients with ALL and AML results
      in low nonrelapse mortality despite high rate of infections and GVHD.
AB  - 28 patients with high-risk acute lymphoblastic (ALL) or acute myelogenous
      leukemia (AML) underwent nonmyeloablative stem cell transplantation (NST) from
      HLA-identical donors because of one or several contraindications against
      myeloablative conditioning. Out of 28 patients, nine (32%) had pulmonary or
      hepatosplenic infiltrates due to invasive fungal infections (IFI) before NST. Out
      of a total of 28 patients, 17 (61%) had uncontrolled leukemia before NST.
      Conditioning was performed with fludarabine 180 mg/m(2), busulfan 8 mg/kg and
      antithymocyte globulin 40 mg/kg. After NST, fever of unknown origin, sepsis or
      pneumonia developed in 18/28 patients (64%) overall. IFI reactivated in 3/9
      patients after NST. Out of, 28 patients, 13 (46%) had late onset of acute graft
      versus-host disease (GvHD), which developed at a median of 83 days after NST.
      GvHD frequently developed after donor lymphocyte infusions. After a median follow
      up of 8 months (2-46 months), 14/28 patients (50%) have died from relapse and
      1/28 patients (4%) has died from sepsis. Among 28 patients, 13 (46%) are alive in
      complete remission (CR). Six of 17 patients (35%) with uncontrolled disease and
      7/11 patients (63%) with CR before NST are alive in CR. Probability of overall
      survival at 2 years is 38%. In summary, NST offers a therapeutic alternative to
      patients with high-risk ALL or AML, who have contraindications against
      conventional high-dose conditioning. Low NRM was encountered despite high
      morbidity, but relapse rate was high. Therefore, controlled studies are necessary
      to elucidate the place of NST in the therapy of high-risk acute leukemias.

PMID- 15448666
TI  - Second autologous transplantation after failure of a first autologous transplant
      in 18 patients with non-Hodgkin's lymphoma.
AB  - High-dose chemotherapy and autologous marrow or peripheral stem cell support
      offers the best chance of cure in some subgroups of patients with non-Hodgkin's
      lymphoma (NHL). Less is known about the role of a second course of myeloablative
      chemotherapy in patients who relapse after a first autologous transplant. The aim
      of this retrospective study was to evaluate the disease outcome, morbidity and
      mortality associated with second autologous transplantation in patients with NHL.
      Between 1985 and 2001, 225 patients who had received autologous transplantation
      for NHL in two institutions in Lyon relapsed. Of these 225 patients 18 underwent
      a second autologous transplantation. The median age at second transplant was 41
      years. There were six indolent lymphomas and 12 aggressive lymphomas. The median
      follow-up from the second transplant was 42 months. The OS rate at 2 and 5 years
      were 58 and 27%, respectively. The PFS rate at 2 and 5 years was 36%. Five
      patients are alive without disease 20 to 100 months after the second transplant.
      Seven patients died of disease recurrence. Four (22%) toxic deaths occurred: one
      of pulmonary fibrosis, one of fungal infection and cardiac failure and two of
      acute leukaemia. A minority of patients with NHL recurrence after a first
      transplant can be cured by a second course of myeloablative chemotherapy at the
      cost however of high-risk toxic death.

PMID- 15448667
TI  - Four-fold staining including CD45 gating improves the sensitivity of
      multiparameter flow cytometric assessment of minimal residual disease in patients
      with acute myeloid leukemia.
AB  - Multiparameter flow cytometry (MFC) is capable of quantifying minimal residual
      disease (MRD) in acute myeloid leukemia (AML). Its broad application, however, is
      limited by a lack of sensitivity in about 20% of patients. CD45 gating may
      improve sensitivity. A broad panel of four-fold combinations of monoclonal
      antibodies including CD45 in each was used to define leukemia-associated aberrant
      immunophenotypes (LAIP), to define their sensitivities in normal bone marrow
      samples, and to compare results to data obtained without CD45 gating using triple
      staining. In 45 patients, a LAIP was defined, 11 normal bone marrow samples were
      analyzed as controls. The median percentage of LAIP-positive AML cells with and
      without CD45 gating was 21.95% (range, 3.31-82.52%) and 20.52% (range, 3.22
      81.94%). The median percentage of LAIP-positive normal bone marrow cells ranged
      from 0.01 to 0.42% (median, 0.02%) and 0.02 to 0.58% (median, 0.15%) with and
      without CD45 gating. The difference of LAIP-positive cells between AML and normal
      bone marrow samples amounted to a median of 3.08 log (range, 1.22-4.01) and 2.28
      log (range, 1.12-3.34) with and without CD45 gating. CD45 gating improves the
      sensitivity of MFC-based MRD monitoring in AML by 1 log.

PMID- 15448668
TI  - Cytogenetic abnormalities in de novo acute myeloid leukemia in adults: relation
      to morphology, age, sex and ethnicity - a single center study from Singapore.
AB  - BACKGROUND: Cytogenetic analysis performed at diagnosis is considered to be the
      most valuable prognostic factor in acute myeloid leukemia (AML). Large systematic
      studies of cytogenetic abnormalities in AML patients from Southeast Asia are not
      available. The karyotypic patterns in AML patients from a single center in
      Singapore were studied and compared with reports from other regions of the world
      to identify possible geographic heterogeneity. METHODS: Analysis was performed on
      501 consecutive de novo AML patients diagnosed according to the FAB criteria in
      the Singapore General Hospital. The cytogenetic findings were analyzed for
      possible associations between karyotypic pattern and the age, gender, ethnicity
      as well as morphological (FAB) subtypes. RESULTS: A total of 454 patients were
      studied of which 275(61%) had abnormal cytogenetics(median age 48 years). The
      t(15;17) and trisomy 8 were the most frequent karyotypic abnormalities - seen in
      52(11%) and 33(7.3%) cases, respectively. Inv(lf) and t(16;16) were uncommon,
      seen only in five (1.1%) cases. The abnormalities del 5/5q and del 7/7q were seen
      in 30(6.6%) and 32(7%) of the cases. Complex karyotypes were seen in 78(17%) of
      the cases.Recurrent cytogenetic abnormalities correlated with the FAB subtypes.
      In all, 21 novel cytogenetic abnormalities were observed. CONCLUSIONS: Certain
      differences such as the age at presentation and frequency of recurrent balanced
      translocations were noted in comparison to previous reports. These point to the
      need for extensive epidemiological studies to clarify the role of genetic as well
      as geographic heterogeneity in the pathogenesis of AML.

PMID- 15448669
TI  - Targeting PML/RARalpha transcript with DNAzymes results in reduction of
      proliferation and induction of apoptosis in APL cells.
AB  - DNAzymes are nucleic acid enzymes that can recognise specific RNA substrate via
      Watson-Crick base pairing and cleave it with multiple turnovers. We have designed
      and examined the effects of DNAzymes targeting the PML/RARalpha fusion gene in
      acute promyelocytic leukaemia (APL). The DNAzymes (DZ1 and DZ3) were designed to
      cleave the PML/RARalpha transcript at the GC nucleotides at the fusion point and
      three nucleotides upstream of that respectively. Disabled DNAzymes were
      synthesised and used as controls. Cell-free cleavage reactions were performed on
      total RNA from NB4 cell line and PML/RARalpha and RARalpha-amplified RNA
      fragments (aRNA). Postcleavage examination showed that DZ1 and DZ3 cleave
      PML/RARalpha efficiently and specifically. NB4 APL cells transfected with DZ1 or
      DZ3 showed a significant suppression of PML/RARalpha protein expression. These
      DNAzymes also inhibited the proliferation of NB4 cells, reduced the viability
      rate, and induced apoptosis in these cells. The disabled DNAzymes showed no
      effect on NB4 cells. The two DNAzymes did not produce any significant effect on
      K562 cells, which were used as control cells. DNAzymes are more resistant to
      serum than ribozymes. These data show that targeting the PML/RARalpha fusion gene
      with DNAzymes can induce apoptosis in APL cells and may have a role in the
      treatment of APL. They also show DNAzymes are promising tools for targeting
      specific genes in leukaemia.

PMID- 15448670
TI  - Accelerated neutrophil apoptosis in neutropenic patients with hepatosplenic
      schistosomiasis is induced by serum Fas ligand.
AB  - Neutropenia in patients with hepatosplenic (HS) schistosomiasis may stem from
      enhanced neutrophil apoptosis. However, the molecular mechanism of neutrophil
      apoptosis has not been clearly defined. Neutrophils harvested from neutropenic
      patients with HS schistosomiasis (n = 25), non-neutropenic patients with
      hepatointestinal (HI) schistosomiasis (n = 10), and age- and sex-matched healthy
      control subjects (n = 10) were examined for the degree of apoptosis after
      incubation with autologous sera. Neutrophil apoptosis was quantified by flow
      cytometry through determination of propidium iodide nuclear staining and
      confirmed by DNA gel electrophoresis at 0 time (fresh neutrophil), 4 and 24 h
      culture. Neutrophils from healthy subjects were also incubated with either 10%
      heterologous normal or neutropenic serum, with and without anti-Fas ligand
      antibody. Serum Fas ligand levels were assessed in sera of patient groups and
      healthy controls by ELISA. Compared with normal controls and HI, HS group
      demonstrated greater neutrophil apoptosis in the presence of autologous serum (P
      < 0.01, < 0.05, respectively). Furthermore, compared with normal neutrophils
      exposed to heterologous normal serum, those exposed to heterologous neutropenic
      serum exhibited higher apoptosis rates (P < 0.01). The apoptotic effect of
      neutropenic sera is attenuated by anti-Fas ligand. Fas expression was
      significantly higher in HS group as compared to both HI and normal healthy
      controls (P < 0.05). Serum Fas ligand levels were significantly higher among HS
      group as compared to both HI and control groups (P < 0.01 for both). Neutrophil
      apoptosis was not correlated to the size of spleen in HS group. In conclusion,
      the rate of neutrophil apoptosis is accelerated in neutropenic HS
      schistosomiasis. These findings suggest that enhanced neutrophil apoptosis
      demonstrated in HS patients is triggered by soluble Fas ligand, which is mostly
      derived from spleen.

PMID- 15448671
TI  - Reduced-intensity conditioning and blood stem cell transplantation from an HLA
      identical sibling for severe aplastic anaemia: two patients with successful
      engraftment but a fatal post-transplant lymphoproliferative disorder in the
      other.
AB  - Allogeneic stem cell transplantation with reduced-intensity conditioning (RIC)
      can be offered to patients who are ineligible for high-dose conditioning because
      of their age or comorbidities. Malignant haematological diseases have so far been
      the most common indication of this new treatment modality; it has been less often
      used for nonmalignant diseases, and there are only a few reports of RIC and
      allotransplantation to treat acquired severe aplastic anaemia (SAA). We report
      two elderly patients (62 and 65 years of age) with SAA who underwent RIC
      (fludarabine + cyclophosphamide + ATG) and HLA-identical sibling allogeneic blood
      stem cell transplantation. Two important findings emerged. First, both of our
      patients who had failed standard immunological treatments and had a heavy
      transfusion history experienced successful engraftment after RIC and blood
      allografting, and one of them continues in full haematological remission 20+
      months post-transplant. Secondly, the other patient died of Epstein-Barr virus
      associated post-transplant lymphoproliferative disorder (PTLD) soon after
      engraftment, which implies that even if PTLD has been described in only few
      single cases after RIC, it may also complicate RIC allotransplants.

PMID- 15448672
TI  - Intravascular lymphoma - a rare cause of hemolytic anemia and neurologic
      disorders.
AB  - Intravascular lymphoma is an uncommon and often overlooked form of non-Hodgkin's
      lymphoma characterized by extensive proliferation of lymphoid cells within the
      lumina of small and medium-sized vessels. Clinical symptoms of the disease are
      variable and often nonspecific, mostly neurologic in nature. With an aggressive
      course, intravascular lymphomatosis has a poor prognosis and is rarely diagnosed
      ante mortem. We describe here a 76-year-old woman with the clinical diagnoses of
      hemolytic anemia and progressive lethargy where intravascular lymphomatosis
      turned out as the underlying cause of the disease.

PMID- 15448673
TI  - Long-term management of chronic DIC associated with inoperable aortic aneurysm
      with low molecular weight heparin.
AB  - Chronic DIC is a rare complication of aortic aneurysm. Surgical correction is the
      treatment of choice but for inoperable patients or those with continued DIC after
      surgery heparin can be used to control the coagulopathy. A case with inoperable
      multiple aortic aneurysm and chronic DIC managed successfully with dalteparin
      over a long period is discussed in this report.

PMID- 15448674
TI  - Plasmodium falciparum causing hemophagocytic syndrome after allogeneic blood stem
      cell transplantation.
AB  - We describe a case of Plasmodium falciparum infection in a 25-year-old male
      patient with a myelodysplastic syndrome, who underwent allogeneic peripheral
      blood stem cell transplantation (PBSCT) in September 2003. Conditioning regimen
      consisted of total body irradiation (10 Gy) and cyclophosphamide 60 mg/kg for 2
      days. A dose of 4 x 10(6) CD34+ cells/kg was transfused. Engraftment was well
      documented on day 17 post-transplantation. Spiking fevers occurred on days 19 and
      21, associated with a pancytopenia, hepatosplenomegaly and neurological signs. P.
      falciparum parasites were found on the peripheral blood smear (parasitemia =
      23%). Marrow aspiration showed P. falciparum parasites and proliferation of
      mature histiocytes with hemophagocytosis. Quinine 10 mg/kg i.v. three times a day
      for 10 consecutive days was given. The fever subsided within 3 days, and
      pancytopenia vanished in 14 days. Parasitemia cleared in 6 days. The patient left
      the unit on day 46 with no further complications. The screening of donors showed
      that infection was acquired from two blood units (from a single donor) given 5
      days before transplantation. We report the first case of profound
      hemophagocytosis in immunosuppressed patient with malaria of high parasitemia
      after a bone marrow transplant.

PMID- 15448675
TI  - Alemtuzumab (Campath 1H) in hairy cell leukaemia relapsing after rituximab
      treatment.

PMID- 15448676
TI  - Primary central nervous system lymphoma (PCNSL) in immunocompetent adults:
      analysis of a retrospective series of patients treated using idarubicin
      containing regimen and radiotherapy.

PMID- 15448677
TI  - Successful management of immune thrombocytopenic purpura with thalidomide in a
      patient with multiple myeloma.

PMID- 15448678
TI  - Multiple myeloma associated with CD4+ large granular lymphocytic leukemia: a
      possible causal relationship.

PMID- 15448679
TI  - tRNA selection and kinetic proofreading in translation.
AB  - Using single-molecule methods we observed the stepwise movement of aminoacyl-tRNA
      (aa-tRNA) into the ribosome during selection and kinetic proofreading using
      single-molecule fluorescence resonance energy transfer (smFRET). Intermediate
      states in the pathway of tRNA delivery were observed using antibiotics and
      nonhydrolyzable GTP analogs. We identified three unambiguous FRET states
      corresponding to initial codon recognition, GTPase-activated and fully
      accommodated states. The antibiotic tetracycline blocks progression of aa-tRNA
      from the initial codon recognition state, whereas cleavage of the sarcin-ricin
      loop impedes progression from the GTPase-activated state. Our data support a
      model in which ribosomal recognition of correct codon-anticodon pairs drives
      rotational movement of the incoming complex of EF-Tu-GTP-aa-tRNA toward peptidyl
      tRNA during selection on the ribosome. We propose a mechanistic model of initial
      selection and proofreading.

PMID- 15448680
TI  - Freely suspended nanocomposite membranes as highly sensitive sensors.
AB  - Highly sensitive sensor arrays are in high demand for prospective applications in
      remote sensing and imaging. Measuring microscopic deflections of compliant
      micromembranes and cantilevers is developing into one of the most versatile
      approaches for thermal, acoustic and chemical sensing. Here, we report on an
      innovative fabrication of compliant nanocomposite membranes with nanoscale
      thickness showing extraordinary sensitivity and dynamic range, which makes them
      candidates for a new generation of membrane-based sensor arrays. These
      nanomembranes with a thickness of 25-70 nm, which can be freely suspended over
      large (hundred micrometres) openings are fabricated with molecular precision by
      time-efficient, spin-assisted layer-by-layer assembly. They are designed as
      multilayered molecular composites made of a combination of polymeric monolayers
      and a metal nanoparticle intralayer. We demonstrate that these nanocomposite
      membranes possess unparalleled sensitivity and a unique autorecovering ability.
      The membrane nanostructure that is responsible for these outstanding properties
      combines multilayered polymer/nanoparticle organization, high polymer-chain
      orientation, and a pre-stretched state.

PMID- 15448681
TI  - Directed assembly of controlled-misorientation bicrystals.
AB  - Grain boundaries play a vital role in determining materials behaviour, and the
      nature of these intercrystalline interfaces is dictated by chemical composition,
      processing history, and geometry (misorientation and inclination). The
      interrelation among these variables and material properties may be systematically
      studied in bicrystals. Conventional bicrystal fabrication offers control over
      these variables, but its ability to mimic grain boundaries in polycrystalline
      materials is ambiguous. Here we describe a novel solid-state process for rapidly
      generating intercrystalline interfaces with controlled geometry and chemistry,
      applicable to a broad range of materials. A fine-grained polycrystalline layer,
      contacted by two appropriately misoriented single-crystal seeds, is consumed by
      an epitaxial solid-state transformation until the directed growth fronts impinge.
      The seed misorientations establish the geometry of the resulting intercrystalline
      boundaries, and the composition of the sacrificial polycrystalline layer
      establishes the chemistry of the boundaries and their adjacent grains. Results
      from a challenging model system, titanium-doped sapphire, illustrate the
      viability of the directed assembly technique for preparing high-quality
      bicrystals in both twist and tilt configurations.

PMID- 15448682
TI  - On the origin of high-temperature ferromagnetism in the low-temperature-processed
      Mn-Zn-O system.
AB  - The recent discovery of ferromagnetism above room temperature in low-temperature
      processed MnO(2)-ZnO has generated significant interest. Using suitably designed
      bulk and thin-film studies, we demonstrate that the ferromagnetism in this system
      originates in a metastable phase rather than by carrier-induced interaction
      between separated Mn atoms in ZnO. The ferromagnetism persists up to
      approximately 980 K, and further heating transforms the metastable phase and
      kills the ferromagnetism. By studying the interface diffusion and reaction
      between thin-film bilayers of Mn and Zn oxides, we show that a uniform solution
      of Mn in ZnO does not form under low-temperature processing. Instead, a
      metastable ferromagnetic phase develops by Zn diffusion into the Mn oxide. Direct
      low-temperature film growth of Zn-incorporated Mn oxide by pulsed laser
      deposition shows ferromagnetism at low Zn concentration for an optimum oxygen
      growth pressure. Our results strongly suggest that the observed ferromagnetic
      phase is oxygen-vacancy-stabilized Mn(2-x)Zn(x)O(3-delta.).

PMID- 15448683
TI  - Selective inactivation or reconstitution of adenosine A2A receptors in bone
      marrow cells reveals their significant contribution to the development of
      ischemic brain injury.
AB  - Inactivation of the adenosine A(2A) receptor (A(2A)R) consistently protects
      against ischemic brain injury and other neural insults, but the relative
      contribution of A(2A)Rs on peripheral inflammatory cells versus A(2A)Rs expressed
      on neurons and glia is unknown. We created a chimeric mouse model in which
      A(2A)Rs on bone marrow-derived cells (BMDCs) were selectively inactivated or
      reconstituted by bone marrow transplantation. Selective reconstitution of A(2A)Rs
      on BMDCs (A(2A)R knockout mice transplanted with wild-type bone marrow cells)
      largely reinstates ischemic brain injury in global A(2A)R knockout mice.
      Conversely, selective inactivation of A(2A)Rs on BMDCs (wild-type mice
      transplanted with A(2A)R knockout bone marrow cells) attenuates infarct volumes
      and ischemia-induced expression of several proinflammatory cytokines in the
      brain, but exacerbates ischemic liver injury. These results indicate that the
      A(2A)R-stimulated cascade in BMDCs is an important modulator of ischemic brain
      injury and that ischemic brain and liver injuries are regulated distinctly by
      A(2A)Rs on BMDCs.

PMID- 15448684
TI  - Neuromedin U has a novel anorexigenic effect independent of the leptin signaling
      pathway.
AB  - Neuromedin U (NMU) is a hypothalamic neuropeptide that regulates body weight and
      composition. Here we show that mice lacking the gene encoding NMU (Nmu(-/-) mice)
      develop obesity. Nmu(-/-) mice showed increased body weight and adiposity,
      hyperphagia, and decreased locomotor activity and energy expenditure. Obese Nmu(
      /-) mice developed hyperleptinemia, hyperinsulinemia, late-onset hyperglycemia
      and hyperlipidemia. Notably, however, treatment with exogenous leptin was
      effective in reducing body weight in obese Nmu(-/-) mice. In addition, central
      leptin administration did not affect NMU gene expression in the hypothalamus of
      rats. These results indicate that NMU plays an important role in the regulation
      of feeding behavior and energy metabolism independent of the leptin signaling
      pathway. These characteristic functions of NMU may provide new insight for
      understanding the pathophysiological basis of obesity.

PMID- 15448685
TI  - 4-1BB-mediated immunotherapy of rheumatoid arthritis.
AB  - Collagen type II-induced arthritis is a CD4(+) T-cell-dependent chronic
      inflammation in susceptible DBA/1 mice and represents an animal model of human
      rheumatoid arthritis. We found that development of this condition, and even
      established disease, are inhibited by an agonistic anti-4-1BB monoclonal
      antibody. Anti-4-1BB suppressed serum antibodies to collagen type II and CD4(+) T
      cell recall responses to collagen type II. Crosslinking of 4-1BB evoked an
      antigen-specific, active suppression mechanism that differed from the results of
      blocking the interaction between 4-1BB and its ligand, 4-1BBL. Anti-4-1BB
      monoclonal antibodies induced massive, antigen-dependent clonal expansion of
      CD11c(+)CD8(+) T cells and accumulation of indoleamine 2,3-dioxygenase in
      CD11b(+) monocytes and CD11c(+) dendritic cells. Both anti-interferon-gamma and 1
      methyltryptophan, a pharmacological inhibitor of indoleamine 2,3-dioxygenase,
      reversed the anti-4-1BB effect. We conclude that the suppression of collagen
      induced arthritis was caused by an expansion of new CD11c(+)CD8(+) T cells, and
      that interferon-gamma produced by these cells suppresses antigen-specific CD4(+)
      T cells through an indoleamine 2,3-dioxygenase-dependent mechanism.

PMID- 15448686
TI  - Central memory T cells mediate long-term immunity to Leishmania major in the
      absence of persistent parasites.
AB  - Infection with Leishmania major induces a protective immune response and long
      term resistance to reinfection, which is thought to depend upon persistent
      parasites. Here we demonstrate that although effector CD4(+) T cells are lost in
      the absence of parasites, central memory CD4(+) T cells are maintained. Upon
      secondary infection, these central memory T cells become tissue-homing effector T
      cells and mediate protection. Thus, immunity to L. major is mediated by at least
      two distinct populations of CD4(+) T cells: short-lived pathogen-dependent
      effector cells and long-lived pathogen-independent central memory cells. These
      data suggest that central memory T cells should be the targets for nonlive
      vaccines against infectious diseases requiring cell-mediated immunity.

PMID- 15448687
TI  - Possible novel therapy for diabetes with cell-permeable JNK-inhibitory peptide.
AB  - The JNK pathway is known to be activated in several tissues in the diabetic
      state, and is possibly involved in the development of insulin resistance and
      suppression of insulin biosynthesis. Here we show a potential new therapy for
      diabetes using cell-permeable JNK-inhibitory peptide. Intraperitoneal
      administration of the peptide led to its transduction into various tissues in
      vivo, and this treatment markedly improved insulin resistance and ameliorated
      glucose tolerance in diabetic mice. These data indicate that the JNK pathway is
      critically involved in diabetes and that the cell-permeable JNK-inhibitory
      peptide may have promise as a new therapeutic agent for diabetes.

PMID- 15448688
TI  - Nonsteroidal anti-inflammatory drugs lower Abeta42 and change presenilin 1
      conformation.
AB  - Recent reports suggest that some commonly used nonsteroidal anti-inflammatory
      drugs (NSAIDs) unexpectedly shift the cleavage products of amyloid precursor
      protein (APP) to shorter, less fibrillogenic forms, although the underlying
      mechanism remains unknown. We now demonstrate, using a fluorescence resonance
      energy transfer method, that Abeta(42)-lowering NSAIDs specifically affect the
      proximity between APP and presenilin 1 and alter presenilin 1 conformation both
      in vitro and in vivo, suggesting a novel allosteric mechanism of action.

PMID- 15448689
TI  - Induction of T helper type 1-like regulatory cells that express Foxp3 and protect
      against airway hyper-reactivity.
AB  - The range of regulatory T cell (T(R) cell) types that control immune responses is
      poorly understood. We describe here a population of T(R) cells that developed in
      vivo from naive CD4(+)CD25(-) T cells during a T helper type 1 (T(H)1)-polarized
      response, distinct from CD25(+) T(R) cells. These antigen-specific T(R) cells
      were induced by CD8alpha(+) DCs, produced both interleukin 10 and interferon
      gamma, and potently inhibited the development of airway hyper-reactivity. These
      T(R) cells expressed the transcription factors Foxp3 and T-bet, indicating that
      these T(R) cells are related to T(H)1 cells. Thus, adaptive T(R) cells are
      heterogeneous and comprise T(H)1-like T(R) cells as well as previously described
      T(H)2-like T(R) cells, which express Foxp3 and are induced during the development
      of respiratory tolerance by CD8alpha(-) DCs.

PMID- 15448690
TI  - Function of the drosophila pattern-recognition receptor PGRP-SD in the detection
      of Gram-positive bacteria.
AB  - The activation of an immune response requires recognition of microorganisms by
      host receptors. In drosophila, detection of Gram-positive bacteria is mediated by
      cooperation between the peptidoglycan-recognition protein-SA (PGRP-SA) and Gram
      negative binding protein 1 (GNBP1) proteins. Here we show that some Gram-positive
      bacterial species activate an immune response in a PGRP-SA- and GNBP1-independent
      manner, indicating that alternative receptors exist. Consistent with this, we
      noted that PGRP-SD mutants were susceptible to some Gram-positive bacteria and
      that a loss-of-function mutation in PGRP-SD severely exacerbated the PGRP-SA and
      GNBP1 mutant phenotypes. These data indicate that PGRP-SD can function as a
      receptor for Gram-positive bacteria and shows partial redundancy with the PGRP-SA
      GNBP1 complex.

PMID- 15448691
TI  - Nonsense surveillance regulates expression of diverse classes of mammalian
      transcripts and mutes genomic noise.
AB  - Premature termination codons induce rapid transcript degradation in eukaryotic
      cells through nonsense-mediated mRNA decay (NMD). This pathway can modulate
      phenotypes arising from nonsense or frameshift mutations, but little is known
      about the physiologic role of NMD in higher eukaryotes. To address this issue, we
      examined expression profiles in mammalian cells depleted of Rent1 (also called
      hUpf1), a factor essential for NMD. Upregulated transcripts included those with
      upstream open reading frames in the 5' untranslated region, alternative splicing
      that introduces nonsense codons or frameshifts, introns in the 3' untranslated
      region or selenocysteine codons. Transcripts derived from ancient transposons and
      endogenous retroviruses were also upregulated. These RNAs are unified by the
      presence of a spliced intron at least 50 nucleotides downstream of a termination
      codon, a context sufficient to initiate NMD. Consistent with direct regulation by
      NMD, representative upregulated transcripts decayed more slowly in cells
      deficient in NMD. In addition, inhibition of NMD induced by amino acid starvation
      upregulated transcripts that promote amino acid homeostasis. These results
      document that nonsense surveillance is a crucial post-transcriptional regulatory
      event that influences the expression of broad classes of physiologic transcripts,
      has been functionally incorporated into essential homeostatic mechanisms and
      suppresses expression of evolutionary remnants.

PMID- 15448692
TI  - Metabolic gene-deletion strains of Escherichia coli evolve to computationally
      predicted growth phenotypes.
AB  - Genome-scale metabolic models have a promising ability to describe cellular
      phenotypes accurately. Here we show that strains of Escherichia coli carrying a
      deletion of a single metabolic gene increase their growth rates (by 87% on
      average) during adaptive evolution and that the endpoint growth rates can be
      predicted computationally in 39 of 50 (78%) strains tested. These results show
      that computational models can be used to predict the eventual effects of genetic
      modifications.

PMID- 15448693
TI  - A module map showing conditional activity of expression modules in cancer.
AB  - DNA microarrays are widely used to study changes in gene expression in tumors,
      but such studies are typically system-specific and do not address the
      commonalities and variations between different types of tumor. Here we present an
      integrated analysis of 1,975 published microarrays spanning 22 tumor types. We
      describe expression profiles in different tumors in terms of the behavior of
      modules, sets of genes that act in concert to carry out a specific function.
      Using a simple unified analysis, we extract modules and characterize gene
      expression profiles in tumors as a combination of activated and deactivated
      modules. Activation of some modules is specific to particular types of tumor; for
      example, a growth-inhibitory module is specifically repressed in acute
      lymphoblastic leukemias and may underlie the deregulated proliferation in these
      cancers. Other modules are shared across a diverse set of clinical conditions,
      suggestive of common tumor progression mechanisms. For example, the bone
      osteoblastic module spans a variety of tumor types and includes both secreted
      growth factors and their receptors. Our findings suggest that there is a single
      mechanism for both primary tumor proliferation and metastasis to bone. Our
      analysis presents multiple research directions for diagnostic, prognostic and
      therapeutic studies.

PMID- 15448695
TI  - A new effector pathway links ATM kinase with the DNA damage response.
AB  - The related kinases ATM (ataxia-telangiectasia mutated) and ATR (ataxia
      telangiectasia and Rad3-related) phosphorylate a limited number of downstream
      protein targets in response to DNA damage. Here we report a new pathway in which
      ATM kinase signals the DNA damage response by targeting the transcriptional
      cofactor Strap. ATM phosphorylates Strap at a serine residue, stabilizing nuclear
      Strap and facilitating formation of a stress-responsive co-activator complex.
      Strap activity enhances p53 acetylation, and augments the response to DNA damage.
      Strap remains localized in the cytoplasm in cells derived from ataxia
      telangiectasia individuals with defective ATM, as well as in cells expressing a
      Strap mutant that cannot be phosphorylated by ATM. Targeting Strap to the nucleus
      reinstates protein stabilization and activates the DNA damage response. These
      results indicate that the nuclear accumulation of Strap is a critical regulator
      in the damage response, and argue that this function can be assigned to ATM
      through the DNA damage-dependent phosphorylation of Strap.

PMID- 15448696
TI  - Identification of BRCA1-IRIS, a BRCA1 locus product.
AB  - Breast cancer is the most common malignancy among women, and mutations in the
      BRCA genes produce increased susceptibility to these malignancies in certain
      families. Here we identify BRCA1-IRIS as a 1,399-amino-acid BRCA1 gene product
      encoded by an uninterrupted open reading frame that extends from codon 1 of the
      known BRCA1 open reading frame to a termination point 34 triplets into intron 11.
      Unlike full-length BRCA1 (p220), BRCA1-IRIS is exclusively chromatin-associated,
      fails to interact with BARD1 in vivo or in vitro and exhibits unique nuclear
      immunostaining. Unlike BRCA1FL (or p220), BRCA1-IRIS also co-immunoprecipitated
      with DNA-replication-licensing proteins and with known replication initiation
      sites. Suppression of BRCA1-IRIS expression hindered the normal departure of
      geminin from pre-replication complexes, and depressed the rate of cellular DNA
      replication and possibly initiation-related synthesis. In contrast, BRCA1-IRIS
      overexpression stimulated DNA replication. These data imply that endogenous BRCA1
      IRIS positively influences the DNA replication initiation machinery.

PMID- 15448697
TI  - Targeted ubiquitination of CDT1 by the DDB1-CUL4A-ROC1 ligase in response to DNA
      damage.
AB  - Cullins assemble a potentially large number of ubiquitin ligases by binding to
      the RING protein ROC1 to catalyse polyubiquitination, as well as binding to
      various specificity factors to recruit substrates. The Cul4A gene is amplified in
      human breast and liver cancers, and loss-of-function of Cul4 results in the
      accumulation of the replication licensing factor CDT1 in Caenorhabditis elegans
      embryos and ultraviolet (UV)-irradiated human cells. Here, we report that human
      UV-damaged DNA-binding protein DDB1 associates stoichiometrically with CUL4A in
      vivo, and binds to an amino-terminal region in CUL4A in a manner analogous to
      SKP1, SOCS and BTB binding to CUL1, CUL2 and CUL3, respectively. As with SKP1
      CUL1, the DDB1-CUL4A association is negatively regulated by the cullin-associated
      and neddylation-dissociated protein, CAND1. Recombinant DDB1 and CDT1 bind
      directly to each other in vitro, and ectopically expressed DDB1 bridges CDT1 to
      CUL4A in vivo. Silencing DDB1 prevented UV-induced rapid CDT1 degradation in vivo
      and CUL4A-mediated CDT1 ubiquitination in vitro. We suggest that DDB1 targets
      CDT1 for ubiquitination by a CUL4A-dependent ubiquitin ligase, CDL4A(DDB1), in
      response to UV irradiation.

PMID- 15448698
TI  - Dual regulation of Snail by GSK-3beta-mediated phosphorylation in control of
      epithelial-mesenchymal transition.
AB  - The phenotypic changes of increased motility and invasiveness of cancer cells are
      reminiscent of the epithelial-mesenchymal transition (EMT) that occurs during
      embryonic development. Snail, a zinc-finger transcription factor, triggers this
      process by repressing E-cadherin expression; however, the mechanisms that
      regulate Snail remain elusive. Here we find that Snail is highly unstable, with a
      short half-life about 25 min. We show that GSK-3beta binds to and phosphorylates
      Snail at two consensus motifs to dually regulate the function of this protein.
      Phosphorylation of the first motif regulates its beta-Trcp-mediated
      ubiquitination, whereas phosphorylation of the second motif controls its
      subcellular localization. A variant of Snail (Snail-6SA), which abolishes these
      phosphorylations, is much more stable and resides exclusively in the nucleus to
      induce EMT. Furthermore, inhibition of GSK-3beta results in the upregulation of
      Snail and downregulation of E-cadherin in vivo. Thus, Snail and GSK-3beta
      together function as a molecular switch for many signalling pathways that lead to
      EMT.

PMID- 15448699
TI  - Hog1 mediates cell-cycle arrest in G1 phase by the dual targeting of Sic1.
AB  - Activation of stress-activated protein kinases (SAPKs) is essential for proper
      cell adaptation to extracellular stimuli. The exposure of yeast cells to high
      osmolarity, or mutations that lead to activation of the Hog1 SAPK, result in cell
      cycle arrest. The mechanisms by which Hog1 and SAPKs in general regulate cell
      cycle progression are not completely understood. Here we show that Hog1 regulates
      cell cycle progression at the G1 phase by a dual mechanism that involves
      downregulation of cyclin expression and direct targeting of the CDK-inhibitor
      protein Sic1. Hog1 interacts physically with Sic1 in vivo and in vitro, and
      phosphorylates a single residue at the carboxyl terminus of Sic1, which, in
      combination with the downregulation of cyclin expression, results in Sic1
      stabilization and inhibition of cell-cycle progression. Cells lacking Sic1 or
      containing a Sic1 allele mutated in the Hog1 phosphorylation site are unable to
      arrest at G1 phase after Hog1 activation, and become sensitive to osmostress.
      Together, our data indicate that the Sic1 CDK-inhibitor is the molecular target
      for the SAPK Hog1 that is required to modulate cell-cycle progression in response
      to stress.

PMID- 15448700
TI  - Calpain-mediated proteolysis of talin regulates adhesion dynamics.
AB  - Dynamic regulation of adhesion complexes is required for cell migration and has
      therefore emerged as a key issue in the study of cell motility. Recent progress
      has been made in defining some of the molecular mechanisms by which adhesion
      disassembly is regulated, including the contributions of adhesion adaptor
      proteins and tyrosine kinases. However, little is known about the potential
      contribution of proteolytic mechanisms to the regulation of adhesion complex
      dynamics. Here, we show that proteolysis of talin by the intracellular calcium
      dependent protease calpain is critical for focal adhesion disassembly. We have
      generated a single point mutation in talin that renders it resistant to
      proteolysis by calpain. Quantification of adhesion assembly and disassembly rates
      demonstrates that calpain-mediated talin proteolysis is a rate-limiting step
      during adhesion turnover. Furthermore, we demonstrate that disassembly of other
      adhesion components, including paxillin, vinculin and zyxin, is also dependent on
      the ability of calpain to cleave talin, suggesting a general role for talin
      proteolysis in regulating adhesion turnover. Together, these findings identify
      calpain-mediated proteolysis of talin as a mechanism by which adhesion dynamics
      are regulated.

PMID- 15448701
TI  - DNA demethylation is necessary for the epigenetic reprogramming of somatic cell
      nuclei.
AB  - Nuclear transplantation experiments in amphibia and mammals have shown that
      oocyte and egg cytoplasm can extensively reprogram somatic cell nuclei with new
      patterns of gene expression and new pathways of cell differentiation; however,
      very little is known about the molecular mechanism of nuclear reprogramming. Here
      we have used nuclear and DNA transfer from mammalian somatic cells to analyse the
      mechanism of activation of the stem cell marker gene oct4 by Xenopus oocytes. We
      find that the removal of nuclear protein accelerates the rate of reprogramming,
      but even more important is the demethylation of somatic cell DNA. DNA
      demethylation seems to precede gene reprogramming, and is absolutely necessary
      for oct4 transcription. Reprogramming by oocytes occurs in the absence of DNA
      replication and RNA/protein synthesis. It is also selective, operating only on
      the promoter, but not enhancers, of oct4; both a putative Sp1/Sp3 and a GGGAGGG
      binding site are required for demethylation and transcription. We conclude that
      the demethylation of promoter DNA may be a necessary step in the epigenetic
      reprogramming of somatic cell nuclei.

PMID- 15448702
TI  - Recruitment of Xenopus Scc2 and cohesin to chromatin requires the pre-replication
      complex.
AB  - Cohesin is a multi-subunit, ring-shaped protein complex that holds sister
      chromatids together from the time of their synthesis in S phase until they are
      segregated in anaphase. In yeast, the loading of cohesin onto chromosomes
      requires the Scc2 protein. In vertebrates, cohesins first bind to chromosomes as
      cells exit mitosis, but the mechanism is unknown. Concurrent with cohesin
      binding, pre-replication complexes (pre-RCs) are assembled at origins of DNA
      replication through the sequential loading of the initiation factors ORC, Cdc6,
      Cdt1 and MCM2-7 (the 'licensing' reaction). In S phase, the protein kinase Cdk2
      activates pre-RCs, causing origin unwinding and DNA replication. Here, we use
      Xenopus egg extracts to show that the recruitment of cohesins to chromosomes
      requires fully licensed chromatin and is dependent on ORC, Cdc6, Cdt1 and MCM2-7,
      but is independent of Cdk2. We further show that Xenopus Scc2 is required for
      cohesin loading and that binding of XScc2 to chromatin is MCM2-7 dependent. Our
      results define a novel pre-RC-dependent pathway for cohesin recruitment to
      chromosomes in a vertebrate model system.

PMID- 15448703
TI  - Electromechanical integration of cardiomyocytes derived from human embryonic stem
      cells.
AB  - Cell therapy is emerging as a promising strategy for myocardial repair. This
      approach is hampered, however, by the lack of sources for human cardiac tissue
      and by the absence of direct evidence for functional integration of donor cells
      into host tissues. Here we investigate whether cells derived from human embryonic
      stem (hES) cells can restore myocardial electromechanical properties.
      Cardiomyocyte cell grafts were generated from hES cells in vitro using the
      embryoid body differentiating system. This tissue formed structural and
      electromechanical connections with cultured rat cardiomyocytes. In vivo
      integration was shown in a large-animal model of slow heart rate. The
      transplanted hES cell-derived cardiomyocytes paced the hearts of swine with
      complete atrioventricular block, as assessed by detailed three-dimensional
      electrophysiological mapping and histopathological examination. These results
      demonstrate the potential of hES-cell cardiomyocytes to act as a rate-responsive
      biological pacemaker and for future myocardial regeneration strategies.

PMID- 15448704
TI  - Lumenal gating mechanism revealed in calcium pump crystal structures with
      phosphate analogues.
AB  - P-type ion transporting ATPases are ATP-powered ion pumps that establish ion
      concentration gradients across biological membranes. Transfer of bound cations to
      the lumenal or extracellular side occurs while the ATPase is phosphorylated. Here
      we report at 2.3 A resolution the structure of the calcium-ATPase of skeletal
      muscle sarcoplasmic reticulum, a representative P-type ATPase that is
      crystallized in the absence of Ca2+ but in the presence of magnesium fluoride, a
      stable phosphate analogue. This and other crystal structures determined
      previously provide atomic models for all four principal states in the reaction
      cycle. These structures show that the three cytoplasmic domains rearrange to move
      six out of ten transmembrane helices, thereby changing the affinity of the Ca2+
      binding sites and the gating of the ion pathway. Release of ADP triggers the
      opening of the lumenal gate and release of phosphate its closure, effected mainly
      through movement of the A-domain, the actuator of transmembrane gates.

PMID- 15448705
TI  - Inhibitory effects of autoantibodies on the muscarinic receptors in Sjogren's
      syndrome.
AB  - Sjogren's syndrome (SS) is a systemic autoimmune disease that involves reduced
      salivary secretions. Recently, circulating autoantibodies from SS patients
      against the type 3 muscarinic cholinergic receptor (M3R) has been reported in the
      sera of SS patients. However, the role of these autoantibodies in the development
      of SS has not been elucidated. In this study, purified IgG was obtained from the
      sera of 11 SS patients, and its inhibitory effect on the M3R of the salivary
      glands was evaluated using RT-PCR, microspectrofluorimetry, immunohistochemistry,
      and Western blot analysis. Stimulation with carbachol (CCh) evoked a [Ca2+]i
      transient in the fura-2 loaded HSG cells. However, pretreatment of the cells with
      SS IgG (0.5 mg/ml) for 12 or 24 h significantly reduced the magnitude of the CCh
      induced [Ca2+]i transient (CICT). We found that the magnitude of CICT was
      decreased by 62-45% when cells were pretreated with the SS IgG. However, the
      [Ca2+]i response to ATP was not altered by the pretreatment of SS IgG. The effect
      of SS IgG on CICT was abrogated by the inclusion of excessive competitive
      peptides that encode the amino-acid sequence of M3R, which was not recapitulated
      by nonspecific peptides. The inhibitory effect of SS IgG on the aquaporin (AQP)-5
      expression was also examined. After confirming the apical localization of AQP-5
      along with its increase by pilocarpine (10(-5) M), we examined whether SS IgG had
      an effect on pilocarpine-induced AQP-5 trafficking to the apical membrane (APM)
      using rat parotid acinar cells. After incubating the cells with SS IgG for 12 h,
      the amount of pilocarpine-induced AQP-5 significantly decreased compared to the
      control groups. In conclusion, autoantibodies from the SS patients inhibit the
      function of the human M3R that is mediated by Ca2+ mobilization and AQP-5
      trafficking. Our results could partly explain the underlying mechanisms of
      glandular dysfunction and associated features of impaired autonomic function in
      SS patients.

PMID- 15448706
TI  - IL-12 p40 prevents the development of chronic enterocolitis in IL-10-deficient
      mice.
AB  - T-helper-1 (Th1) cytokines play an important role in Crohn's disease, and
      interleukin-12 (IL-12), which is composed of two subunits, p40 and p35, drives
      Th1 differentiation. In previous reports, IL-12 p40 was shown to prevent IL-12
      from binding to the receptor. We demonstrate here the effect of IL-12 p40
      overexpression in intestinal epithelia on enterocolitis mediated by Th1 cells in
      IL-10-deficient (IL-10(-/-)) mice on a C57BL/6J background. IL-10 deficient (IL
      10(-/-))/T3b-IL-12 p40+ (IL-12 p40+) mice and IL-10(-/-)/T3b-IL-12 p40- (IL-12
      p40-) mice were generated by crossing T3b-IL-12 p40 transgenic mice and IL-10(-/
      ) mice. At 8 weeks of age, IL-12 p40+ mice did not show any clinical
      manifestations of colitis. The colon length of IL-12 p40- mice became shorter
      than that of IL-12 p40+ mice. The histological score of IL-12 p40+ mice was
      lower. Interferon-gamma (IFN-gamma) production was suppressed in both the
      mesenteric lymph node cell culture and colon tissue culture of IL-12 p40+ mice.
      There was no significant difference in IL-4 production and tumor necrosis factor
      alpha (TNF-alpha) production between the two groups. These results show that
      overexpression of IL-12 p40 in intestinal epithelia prevents enterocolitis in IL
      10(-/-) mice by suppressing IFN-gamma production, and suggest a potential
      clinical application of IL-12 p40 for Crohn's disease. Furthermore, these results
      also suggest that local gene transduction in the intestinal epithelium may be a
      potent therapeutic approach for Crohn's disease.

PMID- 15448707
TI  - Control of Salmonella dissemination in vivo by macrophage inflammatory protein
      (MIP)-3alpha/CCL20.
AB  - While chemokines are clearly important in the generation of protective immunity,
      the role of individual chemokines in the control of bacterial infection is still
      poorly understood. In this study, we investigated the role of macrophage
      inflammatory protein (MIP)-3alpha/CCL20, a chemokine that attracts activated T
      and B lymphocytes and immature dendritic cells, in host responses to bacterial
      infection. CCL20 production was induced in subcutaneous tissue in the BALB/c
      mouse in response to Salmonella enteritidis, Staphylococcus aureus and zymosan,
      with S. enteritidis being the most potent. S. enteritidis induced CCL20
      production in the spleen following either oral administration or injection into
      the peritoneal cavity. In contrast, no increase was observed in the Peyer's
      patches. In this model, following intraperitoneal injection, dose-dependent
      colonization of the spleen and Peyer's patches by S. enteritidis, expression of
      IFNgamma and IL-4, and production of antibodies against the S. enteritidis
      surface antigen SefA were observed. Prior treatment with neutralizing antibodies
      against CCL20 enhanced bacterial dissemination to the spleen and Peyer's patches
      and strongly biased the IFNgamma/IL-4 ratio towards a type 2 profile in the
      spleen, while the humoral response was unaffected. In contrast, treatment with
      neutralizing anti-MIP-1alpha/CCL3 antibodies enhanced the bacterial burden in the
      Peyer's patches but not in the spleen, had no significant effect on the cytokine
      ratio, but significantly inhibited anti-SefA production. Together, these results
      demonstrate an important role for CCL20 in the control of bacterial infection and
      more specifically in the regulation of cell-mediated immunity against
      intracellular bacteria such as S. enteritidis.

PMID- 15448708
TI  - Cardiac involvement in non-human primates infected with the Lyme disease
      spirochete Borrelia burgdorferi.
AB  - To investigate cardiac involvement in the non-human primate (NHP) model of Lyme
      disease, we inoculated 39 adult Macaca mulatta with Borrelia burgdorferi sensu
      stricto strains N40 (BbN40) by needle (N=22, 14 immunocompetent (IC), seven
      permanently immunosuppressed (IS), and four transiently immunosuppressed (TISP))
      or by tick-bite (N=4, all TISP) or strain 297 (Bb297) by needle (N=2 IS), or with
      B. garinii strains Pbi (N=4, 2 TISP and 2 IS), 793 (N=2, TISP) or Pli (N=2,
      TISP). Five uninfected NHPs were used as controls. Infection and inflammation was
      studied in the hearts and the aorta removed at necropsy 2-32 months after
      inoculation by (1) H&E and trichrome-staining; (2) immunohistochemistry and
      digital image analysis; (3) Western blot densitometry; and (4) TaqMan RT-PCR. All
      NHPs inoculated with BbN40 became infected and showed carditis at necropsy. The
      predominant cells were T cells, plasma cells, and macrophages. There was
      increased IgG and IgM in the heart independent of immunosuppression. The B-cell
      chemokine BLC was significantly increased in IS-NHPs. There was increased
      deposition of the complement membrane attack complex (MAC) in TISP and IS-NHPs.
      The spirochetal load was very high in all BbN40-inoculated IS-NHPs but minimal if
      any in IC or TISP NHPs. Double-immunostaining revealed that many spirochetes in
      the heart of BbN40-IS NHPs had MAC on their membranes. We conclude that carditis
      in NHPs infected with B. burgdorferi is frequent and can persist for years but is
      mild unless they are immunosupressed.

PMID- 15448709
TI  - Extracellular signal-regulated kinase (ERK) in glucose-induced and endothelin
      mediated fibronectin synthesis.
AB  - Increased extracellular matrix protein deposition and basement membrane
      thickening are important features of diabetic angiopathy. One key matrix protein
      that has been shown to be instrumental in basement membrane thickening is
      fibronectin (FN). We have previously demonstrated that glucose-induced increased
      expression of endothelin-1 (ET-1), may in part, be responsible for increased FN
      expression via nuclear factor-kappaB (NF-kappaB) and activating protein (AP-1)
      activation. The present study was aimed at elucidating the mechanism of ET-1 with
      respect to mitogen-activated protein kinase/extracellular signal-regulated kinase
      (MAPK/ERK) pathway activation and glucose-induced FN upregulation. Human
      endothelial cells were exposed to either low (5 mM) or high (25 mM) glucose
      levels. Cells in low glucose were also treated with ET-1 peptide (5 nM). In
      addition, we treated cells exposed to high glucose levels with specific MAPK/ERK
      inhibitor PD098059 (50 microM), dual ET-receptor antagonist, bosentan (10
      microM), and PKC blocker, chelerythrine (1 microM). Following incubation period,
      RNA and total proteins were extracted for RT-PCR for FN and immunoblot analysis
      of MAPK/ERK activation. Confocal microscopy was performed for analysis of FN
      protein and nuclear localization of activated Elk. Electrophoretic mobility shift
      assay was carried out to detect NF-kappaB and AP-1 activation. Our data
      demonstrates that high glucose-induced upregulation of FN messenger RNA and
      protein levels occur via activation of MAPK/ERK pathway, which was prevented by
      treatment of cells with bosentan, PD098059 and PKC blocker chelerythrine.
      Confocal microscopy demonstrated nuclear localization of phospho-Elk protein.
      Glucose-induced FN expression was also associated with protein kinase C, NF
      kappaB, and AP-1 activation. These results suggested that glucose-induced, ET-
      and PKC-dependent, upregulation of FN is, in part, mediated via MAPK/ERK
      activation.

PMID- 15448710
TI  - MDM2 expression in EBV-infected nasopharyngeal carcinoma cells.
AB  - To understand whether the p53-regulated mdm2 gene expression was altered by the
      Epstein-Barr virus (EBV) in nasopharyngeal carcinoma (NPC), the NPC-TW01 cell
      line was infected by EBV through IgA receptor-mediated endocytosis. The mdm2 gene
      was expressed only in a small fraction of the NPC cell population and could be
      enhanced in the EBV-infected (EBV+) cells. In the animals bearing EBV+ and EBV-
      NPC xenografts, the MDM2+ cells only appeared in clusters in both EBV+ and EBV-
      tumors with stronger expression in EBV+ cells. Cotransfection of pmdm2-Luc plus
      pSV40-p53 plus pCMV-LMP1 in the NPC-TW06 line that had p53 heterozygous point
      mutation showed stronger mdm2 promoter activity than cells cotransfected with
      pmdm2-Luc plus pSV40-p53, but no mdm2 promoter activity was seen in cells
      cotransfected with pmdm2-Luc plus pCMV-LMP1. Only the EBV-LMP1 but not the EBV
      LMP2A gene could enhance p53 to upregulated mdm2 expression. Tumor cells in NPC
      biopsy specimens revealed similar mdm2 expression as in the animal model. It is
      concluded that although EBV can indirectly enhance mdm2 gene expression in tumor
      cells that express this gene, it cannot turn on or directly regulate mdm2
      expression in cells that do not express this gene. In other words, EBV plays a
      role as an enhancer in NPC tumorigenesis.

PMID- 15448713
TI  - [Clinical governance and public health].

PMID- 15448711
TI  - Mice depleted of CD8+ T and NK cells are resistant to injury caused by cecal
      ligation and puncture.
AB  - We previously showed that beta 2 microglobulin knockout mice depleted of NK cells
      by treatment with anti-asialoGM1 (beta2MKO/alphaAsGM1 mice) are resistant to
      sepsis caused by cecal ligation and puncture (CLP). beta2MKO mice possess
      multiple immunological defects including depletion of CD8+ T cells. This study
      was designed to determine the contribution of CD8+ T and NK cell deficiency to
      the resistance of beta2MKO/alphaAsGM1 mice to CLP-induced injury.
      beta2MKO/alphaAsGM1 mice and CD8 knockout mice treated with anti-asialoGM1
      (CD8KO/alphaAsGM1 mice) survived significantly longer than wild-type mice
      following CLP. Improved long-term survival was also observed in wild-type mice
      rendered CD8+ T/NK cell-deficient by treatment with both anti-CD8alpha and anti
      asialoGM1. Blood gas analysis and body temperature measurements showed that CD8+
      T and NK cell-deficient mice have significantly reduced metabolic acidosis and
      less hypothermia compared to control mice at 18 h after CLP. CD8+ T/NK cell
      deficient mice also showed an attenuated proinflammatory response as indicated by
      decreased expression of mRNAs for IL-1, IL-6 and MIP-2 in spleen and heart. IL-6,
      KC and MIP-2 levels in blood and peritoneal fluid were also significantly
      decreased CD8+ T/NK cell-deficient mice compared to controls. CD8+ T/NK cell
      deficient mice exhibited decreased bacterial concentrations in blood, but not in
      peritoneal fluid or lung, compared to wild-type controls. These data show that
      mice depleted of CD8+ T and NK cells exhibit survival benefit, improved
      physiologic function and an attenuated proinflammatory response following CLP
      that is comparable to beta2M/alphaAsGM1 mice.

PMID- 15448714
TI  - [Epidemiologic Study of Mortality during summer 2003 in Italy].
AB  - Following the unusually hot summer this year and the dramatic news from
      neighboring countries such as France, the Italian Minister of Health requested an
      epidemiologic mortality study during summer 2003, to investigate whether there
      had been an excess of deaths in Italy, particularly for the elderly population.
      Communal offices, which provide vital statistics, were asked for the number of
      deaths among resident people, occurred from June 1 to August 31, for 2003 and
      2002, for the 21 Italian regions capitals. A mortality increase of 3,134 deaths
      was observed for 2003; most of them (92%) were people aged 75 years and older.
      The highest increases were observed in the North Western cities (Turin, Milan,
      Genoa). The relationship between mortality and climatic indexes (T. max, Humidex)
      was investigated and a clear correlation was observed.

PMID- 15448715
TI  - Practical aspects of decontamination of the unconventional transmissible agents
      that cause sporadic and variant Creutzfeldt-Jakob disease and other similar human
      diseases.
AB  - Although the unconventional agents that cause transmissible degenerative
      encephalopathies have not yet been completely characterised, they are known to be
      relatively resistant to decontamination procedures that are effective with
      conventional microorganisms. The implications for the safe decontamination and
      sterilisation of devices and instruments used in human medicine are discussed.

PMID- 15448716
TI  - [Epidemic food outbreaks and activities of Department of Prevention: critic
      factors].
AB  - The Authors critically review three food poisoning episodes occurred within the
      coverage area of ASL NA2, and the related epidemiological researches carried out
      by the Prevention Department. Events, methodology, results, strength points, and
      criticalities are singularly described for each episode. Among the main
      criticalities: timeliness, the missed recovery of food samples and the absence of
      a reference head laboratory. In conclusion, the Authors insist on the need to
      select a central referral facility, responsible for coordinating services between
      the Department and all the other facilities within the coverage area.

PMID- 15448717
TI  - [Quality assurance of cooked food in conventional hospital food service].
AB  - The aim of this study was to evaluate the effectiveness of the hospital food
      service of the Azienda in preserving microbiological quality and temperature of
      cooked foods during the distribution to the different wards of the hospital.
      During three years, microbiological parameters and temperatures were monitored in
      the central kitchen before distribution (T0), in the first (T1) and in the last
      ward (T2) of the distribution route during a three-year period for a total of 337
      analytical determinations. Temperature values before distribution improved during
      the study period, whereas the capacity of keeping adequate temperature values
      during the distribution decreased over time, in spite of the introduction of a
      new technology after the first year of the study. No significant deteriorations
      of the microbiological quality of the cooked foods were detected. The results of
      the study clearly indicate that an integrated approach involving new technology,
      work organization and personnel training is needed in preserving food quality in
      hospitals.

PMID- 15448718
TI  - [Water supply and public health].
AB  - EU legislative framework on water for human consumption has recently been deeply
      modified. As from 25 December 2003, the Directive 80/778/EEC has been abrogated
      by the Directive 98/83/EC, transposed into the Italian legislation with the law
      31/2001, which establishes as an inspiring principle the observance of laws
      common to all Member States while leaving them the discretion to introduce
      secondary parametric values. The directive provides that the parametric values
      should be respected until water distribution, by making the final user fall into
      the sphere of responsibility as a responsible of either a public commercial
      concern or a privately-run concern. This piece of legislation lays the foundation
      for an actual cultural revolution and the involvement of all the institutional,
      political and technical components of the territory, the aim being to safeguard a
      property that "belongs to future generations" and, thus, to be protected.

PMID- 15448719
TI  - [Gender issues in safety and health at work - A review].

PMID- 15448720
TI  - Trends in the prescribing of stimulant medication for the treatment of Attention
      Deficit Hyperactivity Disorder in adults in New South Wales.

PMID- 15448721
TI  - Methods for Analyzing the Role of DNA Methylation and Chromatin Structure in
      Regulating T Lymphocyte Gene Expression.
AB  - Chromatin structure, determined in part by DNA methylation, is established during
      differentiation and prevents expression of genes unnecessary for the function of
      a given cell type. We reported that DNA methylation and chromatin structure
      contributes to lymphoid-specific ITGAL (CD11a) and PRF1 (perforin) expression. We
      used bisulfite sequencing to compare methylation patterns in the ITGAL promoter
      and 5' flanking region of T cells and fibroblasts, and in the PRF1 promoter and
      upstream enhancer of CD4+ and CD8+ T cells with fibroblasts. The effects of
      methylation on promoter function were tested using regional methylation of
      reporter constructs, and confirmed by DNA methyltransferase inhibition. The
      relationship between DNA methylation and chromatin structure was analyzed by
      DNaseI hypersensitivity. Herein we described the methods and results in greater
      detail.

PMID- 15448722
TI  - HIF-1: the knowns and unknowns of hypoxia sensing.
AB  - Hypoxia-inducible factor-1 (HIF-1) is a transcriptional activator that functions
      as a master regulator of cellular and systemic oxygen homeostasis. It consists of
      two constitutively produced subunits: HIF-1alpha and HIF-1beta. Under normoxic
      conditions HIF-1alpha undergoes hydroxylation at specific prolyl residues which
      leads to an immediate ubiquitination and subsequent proteasomal degradation of
      the alpha subunit. Additionally, hydroxylation of an asparaginyl residue blocks
      the transcriptional activity of HIF-1 due to inhibition of its interaction with
      co-activators. In contrast, under hypoxic conditions, abolition of prolyl
      hydroxylation results in HIF-1alpha stabilization, whereas the lack of
      asparaginyl hydroxylation allows the transcriptional activity. Additionally, the
      transcriptional activity may be modulated by phosphorylation or redox
      modification of HIF-1. Despite its name, HIF-1 is induced not only in response to
      reduced oxygen availability but also by other stimulants, such as nitric oxide,
      various growth factors, or direct inhibitors of prolyl and asparaginyl
      hydroxylases. Therefore, it seems to be a crucial transcription factor elicited
      by a wide range of stresses such as impaired oxygenation, inflammation, energy
      deprivation, or intensive proliferation. However, the mechanisms of normoxic
      activation, as well as of oxygen sensing, are not yet fully known. Further
      understanding of the processes that control HIF-1 activity will be crucial for
      the development of new diagnostic and therapeutic strategies.

PMID- 15448723
TI  - Viroids: unusual small pathogenic RNAs.
AB  - Viroids are small (about 300 nucleotides), single-stranded, circular, non
      encapsidated pathogenic RNA molecules. They do not code for proteins and thus
      depend on plant host enzymes for their replication and other functions. They
      induce plant diseases by direct interaction with host factors but the mechanism
      of pathogenicity is still unknown. They can alter the expression of selected
      plant genes important for growth and development. Viroids belong to two families,
      the Avsunviroidae and the Pospiviroidae. Viroids of the Avsunviroidae family
      adopt a branched or quasi rod-like secondary structure in their native state.
      Members of the Pospiviroidae family adopt a rod-like secondary structure. In such
      native structures five structural/functional domains have been identified:
      central (C), pathogenicity, variable and two terminal domains. The central
      conserved region (CCR) within the C domain characterizes viroids of the
      Pospiviroidae. Specific secondary structures of this region play an important
      role in viroid replication and processing. Viroids of the Avsunviroidae family
      lack a CCR but possess self-cleaving properties by forming hammerhead ribozyme
      structures; they accumulate and replicate in chloroplasts, whereas members of the
      Pospiviroidae family have a nuclear localization. Viroid replication occurs via a
      rolling circle mechanism using either a symmetric or asymmetric pathway in three
      steps, RNA transcription, processing and ligation.

PMID- 15448724
TI  - Multifunctional role of plant cysteine proteinases.
AB  - Cysteine proteinases also referred to as thiol proteases play an essential role
      in plant growth and development but also in senescence and programmed cell death,
      in accumulation of storage proteins such as in seeds, but also in storage protein
      mobilization. Thus, they participate in both anabolic and catabolic processes. In
      addition, they are involved in signalling pathways and in the response to biotic
      and abiotic stresses. In this review an attempt was undertaken to illustrate
      these multiple roles of cysteine proteinases and the mechanisms underlying their
      action.

PMID- 15448725
TI  - Novel oligosaccharides isolated from Fusarium oxysporum L. rapidly induce PAL
      activity in Rubus cells.
AB  - Activation of the phenolic pathway is known to be part of a defense response
      against cell wall-derived elicitors from pathogens. Many examples of a defense
      response by increasing the synthesis of phenolic compound against the elicitor
      were demonstrated in the past, but the elicitor structure has so far been poorly
      characterized. Our results indicate that a disaccharide fraction containing the
      following structure: alpha-D-mannopyranosyl (1-->2)alpha/beta-D-glucopyranosyl
      and alpha-D-mannopyranosyl (1-->x) inositol, isolated from Fusarium oxysporum L.,
      promotes rapid and transient phenylalanine ammonia lyase activity in Rubus
      fructicosus cells at nanomolar concentration. The disaccharides were isolated by
      size-exclusion chromatography directly from extracts obtained by alkaline
      treatment of F. oxysporum mycelium. Their structure was determined by 500-MHz-1H
      NMR spectroscopy combined with methylation analysis and fast atom bombardment
      mass spectrometry.

PMID- 15448726
TI  - Characterization of dual specificity protein kinase from maize seedlings.
AB  - A protein kinase of 57 kDa, able to phosphorylate tyrosine in synthetic
      substrates pol(Glu4,Tyr1) and a fragment of Src tyrosine kinase, was isolated and
      partly purified from maize seedlings (Zea mays). The protein kinase was able to
      phosphorylate exogenous proteins: enolase, caseins, histones and myelin basic
      protein. Amino acid analysis of phosphorylated casein and enolase, as well as of
      phosphorylated endogenous proteins, showed that both Tyr and Ser residues were
      phosphorylated. Phosphotyrosine was also immunodetected in the 57 kDa protein
      fraction. In the protein fraction there are present 57 kDa protein kinase and
      enolase. This co-purification suggests that enolase can be an endogenous
      substrate of the kinase. The two proteins could be resolved by two-dimensional
      electrophoresis. Specific inhibitors of typical protein-tyrosine kinases had
      essentially no effect on the activity of the maize enzyme. Staurosporine, a
      nonspecific inhibitor of protein kinases, effectively inhibited the 57 kDa
      protein kinase. Also, poly L-lysine and heparin inhibited tyrosine
      phosphorylation by 57 kDa maize protein kinase. The substrate and inhibitor
      specificities of the 57 kDa maize protein kinase phosphorylating tyrosine
      indicate that it is a novel plant dual-specificity protein kinase.

PMID- 15448727
TI  - Kinetics and specificity of guinea pig liver aldehyde oxidase and bovine milk
      xanthine oxidase towards substituted benzaldehydes.
AB  - Molybdenum-containing enzymes, aldehyde oxidase and xanthine oxidase, are
      important in the oxidation of N-heterocyclic xenobiotics. However, the role of
      these enzymes in the oxidation of drug-derived aldehydes has not been
      established. The present investigation describes the interaction of eleven
      structurally related benzaldehydes with guinea pig liver aldehyde oxidase and
      bovine milk xanthine oxidase, since they have similar substrate specificity to
      human molybdenum hydroxylases. The compounds under test included mono-hydroxy and
      mono-methoxy benzaldehydes as well as 3,4-dihydroxy-, 3-hydroxy-4-methoxy-, 4
      hydroxy-3-methoxy-, and 3,4-dimethoxy-benzaldehydes. In addition, various amines
      and catechols were tested with the molybdenum hydroxylases as inhibitors of
      benzaldehyde oxidation. The kinetic constants have shown that hydroxy-, and
      methoxy-benzaldehydes are excellent substrates for aldehyde oxidase (Km values
      5x10(-6) M to 1x10(-5) M) with lower affinities for xanthine oxidase (Km values
      around 10(-4) M). Therefore, aldehyde oxidase activity may be a significant
      factor in the oxidation of the aromatic aldehydes generated from amines and alkyl
      benzenes during drug metabolism. Compounds with a 3-methoxy group showed
      relatively high Vmax values with aldehyde oxidase, whereas the presence of a 3
      hydroxy group resulted in minimal Vmax values or no reaction. In addition, amines
      acted as weak inhibitors, whereas catechols had a more pronounced inhibitory
      effect on the aldehyde oxidase activity. It is therefore possible that aldehyde
      oxidase may be critical in the oxidation of the analogous phenylacetaldehydes
      derived from dopamine and noradrenaline.

PMID- 15448728
TI  - Structural and functional changes of bovine carbonic anhydrase as a consequence
      of temperature.
AB  - The temperature dependence of the activity and structure of the enzyme carbonic
      anhydrase was studied. The Arrhenius plot shows a jump which is seen usually in
      proteins with more than one subunit or with one subunit but more than one domain.
      Since carbonic anhydrase has only one subunit with one domain, the fine
      conformational changes of the protein motifs could only be detected through
      circular dichroism polarimetry. It seems that the jump in Arrhenius plot is a
      result of some slight structural changes in the secondary and tertiary structures
      of the enzyme.

PMID- 15448729
TI  - Restriction analysis of genetic variability of Polish isolates of Tomato black
      ring virus.
AB  - Several different isolates of Tomato black ring virus (TBRV) have been collected
      in Poland from cucumber, tomato, potato and black locust plants. Biological tests
      showed some differences in the range of infected plants and the type of symptoms,
      which was the basis for selection of seven the most biologically different TBRV
      isolates. According to the sequence of TBRV-MJ, several primer pairs were
      designed and almost the entire sequence of both genomic RNAs was amplified. The
      RT-PCR products derived from all tested TBRV isolates were digested by
      restriction enzymes. On the basis of the restriction patterns, the variable and
      the conserved regions of the TBRV genome were defined and the relationships
      between the Polish TBRV isolates established.

PMID- 15448730
TI  - Spontaneous mutagenesis in exponentially growing and stationary-phase, umuDC
      proficient and -deficient, Escherichia coli dnaQ49.
AB  - Spontaneous mutations arise not only in exponentially growing bacteria but also
      in non-dividing or slowly dividing stationary-phase cells. In the latter case
      mutations are called adaptive or stationary-phase mutations. High spontaneous
      mutability has been observed in temperature sensitive Escherichia coli dnaQ49
      strain deficient in 3'-->5' proofreading activity assured by the e subunit of the
      main replicative polymerase, Pol III. The aim of this study was to evaluate the
      effects of the dnaQ49 mutation and deletion of the umuDC operon encoding
      polymerase V (Pol V) on spontaneous mutagenesis in growing and stationary-phase
      E. coli cells. Using the argE3(OC) -->Arg+ reversion system in the AB1157 strain,
      we found that the level of growth-dependent and stationary-phase Arg+ revertants
      was significantly increased in the dnaQ49 mutant at the non-permissive
      temperature of 37 degrees C. At this temperature, in contrast to cultures grown
      at 28 degrees C, SOS functions were dramatically increased. Deletion of the umuDC
      operon in the dnaQ49 strain led to a 10-fold decrease in the level of Arg+
      revertants in cultures grown at 37 degrees C and only to a 2-fold decrease in
      cultures grown at 28 degrees C. Furthermore, in stationary-phase cultures Pol V
      influenced spontaneous mutagenesis to a much lesser extent than in growing
      cultures. Our results indicate that the level of Pol III desintegration,
      dependent on the temperature of incubation, is more critical for spontaneous
      mutagenesis in stationary-phase dnaQ49 cells than the presence or absence of Pol
      V.

PMID- 15448731
TI  - In vivo gene transfer using cetylated polyethylenimine.
AB  - This report describes gene transfer in vitro as well as in vivo using cetylated
      low-molecular mass (600 Da) polyethylenimine (28% of amine groups substituted
      with cetyl moieties), termed CT-PEI. This compound is hydrophobic and has to be
      incorporated into liposomes in order to be suitable for gene transfer studies.
      Serum-induced plasmid DNA degradation assay demonstrated that CT-PEI-containing
      liposomal carriers could protect complexed DNA (probably via condensation). In
      vitro luciferase gene expression achieved using medium supplemented with 10%
      serum was comparable to that achieved in serum-reduced medium and was highest for
      CT-PEI/cholesterol liposomes, followed by CT-PEI/dioleoylphosphatidylcholine
      liposomes and PEI 600 Da (uncetylated) carrier. In vivo systemic transfer into
      mice was most efficient when liposome formulations contained CT-PEI and
      cholesterol. Higher luciferase expression was then observed in lungs than in
      liver. IN CONCLUSION: liposomes containing cetylated polyethylenimine and
      cholesterol are a suitable vehicle for investigating systemic plasmid DNA
      transfer into lungs.

PMID- 15448732
TI  - Preliminary studies of phthalocyanine sensitizers incorporated into human
      leukemia cells from two cell-lines.
AB  - Three phthalocyanine dyes-sensitizers were incorporated into two types of human T
      leukemia cells from two cell-lines: CCRF and MOLT 4. The efficiency of the dye
      incorporation into cells and photochemical properties of stained cells were
      investigated using fluorescence spectroscopy. The dyes exhibited different
      properties in each of the two cell-lines. Small differences in cell membrane
      properties have a strong influence on the efficiency of dye incorporation and on
      the course of photodynamic reaction. It is suggested that, for a given patient,
      an optimal dye-sensitizer should be established before photodynamic treatment.

PMID- 15448733
TI  - Sulforaphane-mediated induction of a phase 2 detoxifying enzyme NAD(P)H:quinone
      reductase and apoptosis in human lymphoblastoid cells.
AB  - The effect of sulforaphane on human lymphoblastoid cells originating from a
      patient of a high cancer risk was studied. Sulforaphane (SFN) is a naturally
      occurring substance of chemopreventive activity. In our study, changes in cell
      growth, induction of apoptosis and phase 2 enzymes as well as glutathione level
      were examined. Apoptosis was tested by confocal microscopy at three stages:
      change in mitochondrial membrane potential, caspase activation and
      phosphatidylserine externalization. We show that SFN increases the activity of
      the detoxification system: it increases quinone reductase activity at low
      concentration (0.5-1 microM) and raises glutathione level in a dose-dependent
      manner. At higher doses (2.5-10 microM) sulforaphane is a cell growth modulator,
      as it caused cell growth cessation (IC50 = 3.875 microM), and apoptosis inducer.
      The results obtained suggest that sulforaphane acts as a chemopreventive agent in
      human lymphoblastoid cells.

PMID- 15448734
TI  - CEA-negative glioblastoma and melanoma cells are sensitive to cytosine
      deaminase/5-fluorocytosine therapy directed by the carcinoembryonic antigen
      promoter.
AB  - Recent studies have suggested that carcinoembryonic antigen (CEA)-promoter
      sequences are active only in CEA-positive cells, filing in the criteria for tumor
      specific targeting of suicide genes. However, the present study on gene therapy
      of colon cancer and cell-specificity of CEA promoter, provide evidence that CEA
      positive and CEA-negative cells transfected with E. coli cytosine deaminase (CD)
      gene under the control of CEA promotor sequence are sensitive to enzyme/pro-drug
      therapy with 5-fluorocytosine (5-FC). Individual clones derived from the CEA
      negative cell lines: melanoma Hs294T and glioblastoma T98G after transfection
      with CD differed profoundly in their sensitivity to 5-FC. The IC50 values for
      several clones of the CEA-negative cells were almost the same as for CEA-positive
      colon cancer cells. Such 5-FC-sensitive clones derived from the population of CEA
      negative cells, present even in small number, because of the very effective
      bystender effect of this enzyme/pro-drug system can cause severe problems during
      therapy by efficiently killing surrounding normal cells. Safety is the major
      issue in gene therapy. Our data suggest that the safety of gene-directed enzyme
      pro-drug therapy (GDEPT) with CEA promoter driven expression of therapeutic genes
      is not so obvious as it has originally been claimed.

PMID- 15448735
TI  - Can transforming growth factor-beta1 and retinoids modify the activity of
      estradiol and antiestrogens in MCF-7 breast cancer cells?.
AB  - Retinoic acid and transforming growth factor-beta (TGF-beta) affect
      differentiation, proliferation and carcinogenesis of epithelial cells. The effect
      of both compounds on the proliferation of cells of the hormone sensitive human
      breast cancer cell line (ER+) MCF-7 was assessed in the presence of estradiol and
      tamoxifen. The assay was based on [3H]thymidine incorporation and the
      proliferative activity of PCNA- and Ki 67-positive cells. The apoptotic index and
      expression of the Bcl-2 and p53 antigens in MCF-7 cells were also determined.
      Exogenous TGF-beta1 added to the cell culture showed antiproliferative activity
      within the concentration range of 0.003-30 ng/ml. Irrespective of TGF-beta1
      concentrations, a marked reduction in the stimulatory action of estradiol (10(-9)
      and 10(-8) M) was observed whereas in combination with tamoxifen (10(-7) and 10(
      6) M) only 30 ng/ml TGF-beta1 caused a statistically significant reduction to
      approximately 30% of the proliferative cells. In further experiments we examined
      the effect of exposure of breast cancer cells to retinoids in combination with
      TGF-beta1. The incorporation of [3H]thymidine into MCF-7 cells was inhibited to
      52 +/- 19% (control =100%) by 3 ng/ml TGF-beta1, and this dose was used
      throughout. It was found that addition of TGF-beta1 and isotretinoin to the
      culture did not decrease proliferation, while TGF-beta1 and tretinoin at low
      concentrations (3 x 10(-8) and 3 x 10(-7) M) reduced the percentage of
      proliferating cells by approximately 30% (67+/-8% and 67+/-5%, P<0.05 compared to
      values in the tretinoin group). Both retinoids also led to a statistically
      significant decrease in the stimulatory effect of 10(-9) M estradiol, attenuated
      by TGF-beta1. In addition, the retinoids in combination with TGF-beta1 and
      tamoxifen (10(-6) M) caused a further reduction in the percentage of
      proliferating cells. Immunocytochemical analysis showed that all the examined
      compounds gave a statistically significant reduction in the percentage of cells
      with a positive reaction to PCNA and Ki 67 antigen. TGF-beta1, isotretinoin and
      tretinoin added to the culture resulted in the lowest percentage of PCNA positive
      cells. However, the lowest fraction of Ki 67 positive cells was observed after
      addition of isotretinoin. The obtained results also confirm the fact that the
      well-known regulatory proteins Bcl-2 and p53 play an important role in the
      regulation of apoptosis in the MCF-7 cell line, with lowered Bcl-2 expression
      accompanying easier apoptotic induction. The majority of the examined compounds
      act via the p53 pathway although some bypass this important proapoptotic factor.

PMID- 15448736
TI  - Detection of circulating breast cancer cells in peripheral blood by a two-marker
      reverse transcriptase-polymerase chain reaction assay.
AB  - The aim of this study was to use a two-marker assay for the detection of breast
      cancer cells circulating in patients' blood. We have applied a PCR-based
      methodology to follow up the possibility of the development of metastatic disease
      in stage I and II patients who had undergone curative surgery. Since the number
      of circulating cancer cells in peripheral blood is very low, the technique for
      their detection needs to be not only highly sensitive, but also very specific.
      The reverse transcriptase-polymerase chain reaction (RT-PCR) technique may
      improve the sensitivity of breast cancer cell detection up to only a few cells
      per one million. The principle of the RT-PCR assay is to amplify a messenger RNA
      characteristic for breast epithelial cells in a blood sample. Since we do not
      expect such cells to be circulating in peripheral blood of healthy subjects,
      detection of the characteristic mRNA should indicate the presence of circulating
      breast cancer cells. We analyzed the usefulness of three mRNA markers:
      cytokeratin 19 (CK19), mammaglobin (hMAM) and beta subunit of human chorionic
      gonadotropin (beta-hCG) for this test. Blood samples (112) were obtained from 55
      patients, in stages I and II, with or without metastasis to regional lymph nodes
      (N0 or N1). We found that a two-marker assay increases the sensitivity of
      detection of breast cancer cells in comparison with a single-marker one.
      Combination of two tumor-specific mRNA markers, hMAM/CK19 or beta-hCG/CK19,
      allowed the detection of circulating breast cancer cells in 65% of N1 patients
      and 38% of N0 patients. By comparison, the combination hMAM/beta-hCG allowed the
      detection of circulating breast cancer cells in the blood of 68% of N1 patients
      and 46% of N0 patients. Addition of the third marker did not significantly
      increase the detection sensitivity.

PMID- 15448737
TI  - Bidirectional regulation of renal cortical Na+,K+-ATPase by protein kinase C.
AB  - We examined the role of protein kinase C (PKC) in the regulation of Na+,K+-
      ATPase activity in the renal cortex. Male Wistar rats were anaesthetized and the
      investigated reagents were infused into the abdominal aorta proximally to the
      renal arteries. A PKC-activating phorbol ester, phorbol 12,13-dibutyrate (PDBu),
      had a dose-dependent effect on cortical Na+,K+-ATPase activity. Low dose of PDBu
      (10(-11) mol/kg per min) increased cortical Na+,K+-ATPase activity by 34.2%,
      whereas high doses (10(-9) and 10(-8) mol/kg per min) reduced this activity by
      22.7% and 35.0%, respectively. PDBu administration caused changes in Na+,K+
      ATPase Vmax without affecting K(0.5) for Na+, K+ and ATP as well as Ki for
      ouabain. The effects of PDBu were abolished by PKC inhibitors, staurosporine,
      GF109203X, and Go 6976. The inhibitory effect of PDBu was reversed by
      pretreatment with inhibitors of cytochrome P450-dependent arachidonate
      metabolism, ethoxyresorufin and 17-octadecynoic acid, inhibitors of
      phosphatidylinositol 3-kinase (PI3K), wortmannin and LY294002, and by actin
      depolymerizing agents, cytochalasin D and latrunculin B. These results suggest
      that PKC may either stimulate or inhibit renal cortical Na+,K+-ATPase. The
      inhibitory effect is mediated by cytochrome P450-dependent arachidonate
      metabolites and PI3K, and is caused by redistribution of the sodium pump from the
      plasma membrane to the inactive intracellular pool.

PMID- 15448738
TI  - Involvement of Na+/H+ exchanger in desmopressin-induced platelet procoagulant
      response.
AB  - Desmopressin (DDAVP) action on platelets is associated with the development of
      procoagulant response but the underlying mechanism of this phenomenon is not
      known. We investigated whether this effect of DDAVP might be due to activation of
      plasma membrane Na+/H+ exchanger. The DDAVP-induced platelet procoagulant
      response, measured as phospholipid-dependent thrombin generation, was dose
      dependent and significantly weaker than that produced by collagen or monensin
      (mimics Na+/H+ antiport). Both the DDAVP- and collagen-produced procoagulant
      responses were less pronounced in the presence of EIPA, an Na+/H+ exchanger
      inhibitor. Flow cytometry studies revealed that in vitro treatment of platelets
      with DDAVP or collagen was associated with the appearance of both degranulated
      (and fragmented) and swollen cells. The DDAVP-evoked rise in size and granularity
      heterogeneity was similar to that produced by collagen or monensin and was not
      observed in the presence of EIPA. Using flow cytometry and annexin V-FITC as a
      probe for phosphatidylserine (PS) we demonstrated increased and uniform binding
      of this marker to all subsets of DDAVP-treated platelet population. The DDAVP
      evoked PS expression was dose dependent, strongly reduced by EIPA and weaker than
      that caused by monensin or collagen. As judged by optical swelling assay, DDAVP
      in a dose dependent manner produced a rise in platelet volume. The swelling was
      inhibited by EIPA and its kinetics was similar to that observed in the presence
      of monensin. Electronic cell-sizing measurements showed an increase in mean
      platelet volume and a decrease in platelet count and platelet crit upon treatment
      with DDAVP. DDAVP elicited a slow (much slower than collagen) alkalinization of
      platelet cytosol. Altogether the data indicate an involvement of Na+/H+ exchanger
      in the generation of procoagulant activity in DDAVP-treated platelets.

PMID- 15448739
TI  - Nitric oxide and platelet energy metabolism.
AB  - This study was undertaken to determine whether nitric oxide (NO) can affect
      platelet responses through the inhibition of energy production. It was found that
      NO donors: S-nitroso-N-acetylpenicyllamine, SNAP, (5-50 microM) and sodium
      nitroprusside, SNP, (5-100 microM) inhibited collagen- and ADP-induced
      aggregation of porcine platelets. The corresponding IC50 values for SNAP and SNP
      varied from 5 to 30 microM and from 9 to 75 microM, respectively. Collagen- and
      thrombin-induced platelet secretion was inhibited by SNAP (IC50 = 50 microM) and
      by SNP (IC50 = 100 microM). SNAP (20-100 microM), SNP (10-200 microM) and
      collagen (20 microg/ml) stimulated glycolysis in intact platelets. The degree of
      glycolysis stimulation exerted by NO donors was similar to that produced by
      respiratory chain inhibitors (cyanide and antimycin A) or uncouplers (2,4
      dinitrophenol). Neither the NO donors nor the respiratory chain blockers affected
      glycolysis in platelet homogenate. SNAP (20-100 microM) and SNP (50-200 microM)
      inhibited oxygen consumption by platelets. The effect of SNP and SNAP on
      glycolysis and respiration was not reduced by 1H-[1,2,4]oxadiazolo-[4,3
      a]quinoxalin-1-one, a selective inhibitor of NO-stimulated guanylate cyclase.
      SNAP (5-100 microM) and SNP (10-300 microM) inhibited the activity of platelet
      cytochrome oxidase and had no effect on NADH:ubiquinone oxidoreductase and
      succinate dehydrogenase. Blocking of the mitochondrial energy production by
      antimycin A slightly affected collagen-evoked aggregation and strongly inhibited
      platelet secretion. The results indicate that: 1) in porcine platelets NO is able
      to diminish mitochondrial energy production through the inhibition of cytochrome
      oxidase, 2) the inhibitory effect of NO on platelet secretion (but not
      aggregation) can be attributed to the reduction of mitochondrial energy
      production.

PMID- 15448740
TI  - Tissue-specific effect of refeeding after short- and long-term caloric
      restriction on malic enzyme gene expression in rat tissues.
AB  - Restricting food intake to a level below that consumed voluntarily (85%, 70% and
      50% of the ad libitum energy intake for 3 or 30 days) and re-feeding ad libitum
      for 48 h results in an increase of malic enzyme (ME) gene expression in rat white
      adipose tissue. The increase of ME gene expression was much more pronounced in
      rats maintained on restricted diet for 30 days than for 3 days. The changes in ME
      gene expression resembled the changes in the content of SREBP-1 in white adipose
      tissue. A similar increase of serum insulin concentration was observed in all
      groups at different degrees of caloric restriction and refed ad libitum for 48 h.
      Caloric restriction and refeeding caused on increase of ME activity also in brown
      adipose tissue (BAT) and liver. However, in liver a significant increase of ME
      activity was found only in rats maintained on the restricted diet for 30 days. No
      significant changes after caloric restriction and refeeding were found in heart,
      skeletal muscle, kidney cortex, and brain. These data indicate that the increase
      of ME gene expression after caloric restriction/refeeding occurs only in
      lipogenic tissues. Thus, one can conclude that caloric restriction/refeeding
      increases the enzymatic capacity for fatty acid biosynthesis.

PMID- 15448741
TI  - Plasma levels of total, free and protein bound thiols as well as sulfane sulfur
      in different age groups of rats.
AB  - The redox status of plasma thiols can be a diagnostic indicator of different
      pathological states. The aim of this study was to identify the age dependent
      changes in the plasma levels of total, free and protein bound glutathione,
      cysteine and homocysteine. The determination was conducted in plasma of three
      groups of rats: 1) young (3-month-old), 2) middle aged (19-month-old), and 3) old
      (31-month-old). Total levels of glutathione, cysteine and homocysteine and their
      respective free and protein-bound fractions decreased with age. The only
      exception was a rise in free homocysteine concentration in the middle group,
      which indicates a different pattern of transformations of this thiol in plasma.
      The drop in the level of protein-bound thiols suggests that the antioxidant
      capacity of plasma diminishes with age, which, consequently, leads to impaired
      protection of -SH groups through irreversible oxidation. The plasma sulfane
      sulfur level also declines with age, which means that aging is accompanied by
      inhibition of anaerobic sulfur metabolism.

PMID- 15448742
TI  - Effect of cadmium on collagen content and solubility in rat bone.
AB  - The toxic action of cadmium in the bone tissue is known, but its mechanisms are
      still unexplained. We examined whether Cd influences collagen content and its
      solubility in the femoral bone of three-week-old female rats exposed to 5 or 50
      mg Cd/l in drinking water. Non-cross linked collagen was extracted with 0.5 M
      acetic acid, and two acid-insoluble collagen fractions were extracted with pepsin
      and 4.0 M guanidine hydrochloride, respectively. SDS/PAGE showed the presence of
      two collagen types, I and V, in all three extracted fractions. Exposure of rats
      to Cd for 6 months increased the amount of acid-soluble collagens type I and V
      and decreased the level of acid-insoluble collagens. The amount of total collagen
      extracted from the bones of rats exposed to 50 mg Cd/l was reduced by about 14%
      as compared to control and those intoxicated with 5 mg Cd/l. The solubility of
      type I bone collagen (determined as the percentage of acetic-soluble fraction of
      total collagen) was increased 2.9- and 3.0-fold in rats intoxicated with 5 and 50
      mg Cd/l, respectively. Similarly, the solubility of type V collagen was increased
      2.3- and 2.7-fold, respectively. Our results indicate that Cd treatment affects
      bone collagen by decreasing its content and increasing its solubility.

PMID- 15448743
TI  - Activity of lysosomal exoglycosidases in submandibular glands of rats intoxicated
      by cadmium at doses related to human chronic environmental and occupational
      exposures.
AB  - Work in cadmium (Cd) smelter and smoking cigarettes damages teeth and oral mucosa
      which are protected by tissue and salivary glycoconjugates: glycoproteins,
      glycolipids, and proteoglycans. We worked out a rat model imitating human
      "environmental" and "occupational" exposure to cadmium using 5 mg Cd and 50 mg
      Cd/l in drinking water, respectively. In submandibulary glands of exposed to Cd
      rats, we found the time and dose dependent accumulation of Cd and simultanous
      decrease in activity of beta-N-acetylhexosaminidase (HEX). In homogenates of
      submandibulary glands of control rats, beta-N-acetylhexosaminidase showed the
      highest activity. The activities of alpha-mannosidase and beta-galactosidase were
      very low. None of these exoglycosidases were inhibited by Cd even at 44 mM
      concentration.

PMID- 15448744
TI  - Thiamine prevents X-ray induction of genetic changes in human lymphocytes in
      vitro.
AB  - The effects of thiamine (vitamin B1) on the level of spontaneous or radiation
      induced genetic changes in human lymphocytes in vitro were studied. Cultured
      lymphocytes were exposed to increasing concentrations of thiamine (0-500
      microg/ml) and irradiated with X-rays. The DNA damage was estimated as the
      frequency of micronuclei and apoptotic or necrotic morphological changes in fixed
      cells. The results show that thiamine alone did not induce genetic changes. A
      significant decrease in the fraction of apoptotic and necrotic cells was observed
      in lymphocytes irradiated in the presence of vitamin B1 at concentrations between
      1-100 microg/ml compared to those irradiated in the absence of thiamine. Vitamin
      B1 at 1 and 10 microg/ml decreased also the extent of radiation-induced formation
      of micronuclei. Vitamin B1 had no effect on radiation-induced cytotoxicity as
      measured by nuclear division index. The results indicate that vitamin B1 protects
      human cells from radiation-induced genetic changes.

PMID- 15448745
TI  - Influence of BCR/ABL fusion proteins on the course of Ph leukemias.
AB  - The hallmark of chronic myeloid leukemia (CML) and a subset of acute
      lymphoblastic leukemia (ALL) is the presence of the Philadelphia chromosome as a
      result of the t(9;22) translocation. This gene rearrangement results in the
      production of a novel oncoprotein, BCR/ABL, a constitutively active tyrosine
      kinase. There is compelling evidence that the malignant transformation by BCR/ABL
      is critically dependent on its Abl tyrosine kinase activity. Also the bcr part of
      the hybrid gene takes part in realization of the malignant phenotype. We supposed
      that additional mutations accumulate in this region of the BCR/ABL oncogene
      during the development of the malignant blast crisis in CML patients. In ALL
      patients having p210 fusion protein the mutations were supposed to be
      preexisting. Sequencing of PCR product of the BCR/ABL gene (Dbl, PH region)
      showed that along with single-nucleotide substitutions other mutations, mostly
      deletions, had occurred. In an ALL patient a deletion of the 5th exon was
      detected. The size of the deletions varied from 36 to 220 amino acids. For one
      case of blast crisis of CML changes in the character of actin organization were
      observed. Taking into account the functional role of these domains in the cell an
      etiological role of such mutations on the disease phenotype and leukemia
      progression is plausible.

PMID- 15448746
TI  - Antitumour activity of Salmonella typhimurium VNP20047 in B16(F10) murine
      melanoma model.
AB  - A tumour therapy is proposed based on attenuated Salmonella typhimurium VNP20047
      expressing the Escherichia coli cytosine deaminase gene. VNP20047 was
      administered intravenously to B16(F10) melanoma-bearing C57BL/6 mice. VNP20047
      proliferated within tumours and livers regardless of the initial inoculum dose.
      After 10 days the number of bacteria increased in livers up to 4.2 x 10(6) cfu/g
      and decreased in tumours down to 5.9 x 10(6) cfu/g. VNP20047 at 1 x 10(5)
      cfu/mouse, when combined with 5-fluorocytosine, inhibited tumour growth by 85%
      without prolonging animal survival. Histology studies revealed severe lesions in
      tumours and livers. These data suggest that S. typhimurium VNP20047 induced
      inflammatory responses, even though the strain was attenuated.

PMID- 15448747
TI  - Role of rpoS in the regulation of glyoxalase III in Escherichia coli.
AB  - Methylglyoxal is an endogenous electrophile produced in Escherichia coli by the
      enzyme methylglyoxal synthase to limit the accumulation of phosphorylated sugars.
      In enteric bacteria methylglyoxal is detoxified by the glutathione-dependent
      glyoxalase I/II system, by glyoxalase III, and by aldehyde reductase and alcohol
      dehydrogenase. Here we demonstrate that glyoxalase III is a stationary-phase
      enzyme. Its activity reached a maximum at the entry into the stationary phase and
      remained high for at least 20 h. An rpoS- mutant displayed normal glyoxalase I
      and II activities but was unable to induce glyoxalase III in stationary phase. It
      thus appears that glyoxalase III is regulated by rpoS and might be important for
      survival of non-growing E. coli cultures.

PMID- 15448748
TI  - Human osteosarcoma xenografts and their sensitivity to chemotherapy.
AB  - Despite the increased survival rates of osteosarcoma patients attributed to
      adjuvant chemotherapy, at least one third of the patients still die due to their
      disease. Further improvements in the management of osteosarcoma may rely on a
      more individualised treatment strategy, as well as on the introduction of new
      drugs. To aid in the preclinical evaluation of new candidate substances against
      osteosarcoma, we have established 11 human osteosarcoma xenograft lines and
      characterised them with regard to response to five different reference drugs.
      Doxorubicin, cisplatin methotrexate, ifosfamide and lomustine were effective in
      3/11, 3/11, 1/10, 5/11 and 4/11 of the xenografts, respectively. Five xenografts
      were resistant to all compounds tested. We also assessed the mRNA expression
      levels of the xenografts for the O(6)-Methylguanine DNA Methyltransferase (MGMT),
      DNA topoisomerase II- (Topo II)-alpha, Gluthathione-S-transferase (GST)-pi,
      Multidrug-resistance related protein (MRP) 1 and Multidrug-resistance (MDR) 1
      genes. There was an inverse correlation between the transcript levels of GST-pi
      and doxorubicin growth inhibition (r=-0.66; p<0.05), and between the transcript
      levels of MGMT and the effect of lomustine (r=-0.72; p<0.01), whereas the
      expression of MRP1 and cisplatin growth inhibition was positively correlated
      (r=0.82; p<0.005). This panel of xenografts should constitute a good tool for
      pharmacological and molecular studies in osteosarcoma.

PMID- 15448749
TI  - Chromosomal aberrations accumulate in polyploid cells of high-grade squamous
      intraepithelial lesions (HSIL).
AB  - Persistant infection with human papillomavirus (HPV) of the uterine cervix is
      related with cytological atypia (SIL), the oncogenic potential of which is
      unclear in a given time point of monitoring. HPV-induced genetic instability
      result in polyploidization as well as in low frequency random chromosome
      aberrations in squamous cells. In the present work we analyzed whether highly
      polyploid/aneuploid cells reflect genomic changes at the chromosomal level. 13
      samples with the cytological diagnosis of HSIL were analyzed for HPV type and
      nuclear DNA content measured by laser scanning cytometry (LSC). Hyperdiploid
      cells with >5c and with >9c DNA content were further analyzed for numerical
      aberrations of the chromosomes 3 and 17 by fluorescence in situ hybridization
      (FISH) following repositioning. Cells with >5c DNA content were found more
      frequently than cells with >9c DNA content (5-98 and 1-44 cells, respectively).
      The FISH analysis demonstrated frequent polysomies, however, the rate of aneusomy
      (other than 2, 4, 8 or 16 chromosome copies) was significantly higher in cells
      with >9c DNA content than in cells with >5c DNA content or the normal diploid
      cells. The imbalance of chromosome 3 and 17 copy number was also increased in
      cells with >9c DNA content. Moreover, in three out of the 13 analyzed HSIL
      samples, recurrent abnormal chromosome 3/17 ratio was demonstrated in a
      significant part of the cells, indicating a common origin of these cells. Highly
      polyploid/aneuploid cells in HSIL accumulate cytogenetic aberrations detectable
      by FISH analysis. These cells may reflect early changes with tumorigenic
      potential in a very concentrated fashion.

PMID- 15448750
TI  - Alterations of microvascular density in bone metastases of adenocarcinomas.
AB  - Bone may provide an extremely fertile microenvironment for angiogenesis.
      Experimental investigations indicate angiogenesis as a major regulator of bone
      metastasis development. Vascularization and angiogenic potential is known for
      most of the primary tumor types, but no studies investigated angiogenesis in bone
      metastases of human cancers. We have evaluated microvessel density of bone
      metastases of various cancer types (all adenocarcinomas) and compared to their
      primary tumors in paraffin samples of 39 patients. Microvessel density was
      determined by using the hot spot method and the blood vessel marker, CD34. The
      most vascularized adenocarcinoma was found to be renal cell cancer followed by
      lung adenocarcinoma, while breast cancer was heterogenous in this respect. Two
      patterns of modulation of the angiogenic phenotype in the bone metastases emerged
      in this study, which seemed to be cancer type specific: decreased angiogenic
      potential characterizing 45% of renal cell cancers and breast cancers of high
      vascularity in their primary, and increased angiogenic potential characterizing
      40% of lung adenocarcinomas and breast cancers of low vascularity in their
      primary lesion. Our data demonstrate that i., the vascularization of bone
      metastases is frequently altered compared to the primary tumors, ii., patterns
      are different in the case of various cancer types. The tumor-type specific
      alterations of the angiogenic phenotype of cancers, metastatic to the bone, can
      have a clinical significance when angiosuppressive therapies are considered.

PMID- 15448751
TI  - Apoptosis in transitional cell carcinoma of bladder and its relation to
      proliferation and expression of p53 and bcl-2.
AB  - Transitional cell carcinoma of bladder (TCC) is a relatively common cancer among
      men. Tumor progression is associated with expression or modulation of several
      gene products that control apoptosis and proliferation. Apoptosis is a negative
      growth regulatory mechanism in tumors. The aim of this study is to examine
      apoptosis and related regulatory molecular markers in a group of patients with
      TCC. Paraffinembedded tissues from 49 patients with TCC were examined for the
      expression of bcl-2, p53 and Ki-67 by immunohistochemistry. Apoptosis was
      detected by TUNEL method. Correlation between apoptotic index (AI), proliferation
      index (PI) and bcl-2 and p53 expression with each other and with pathological
      grade was determined. Apoptosis was observed in 28.1% of TCC cases. The mean AI
      of all cases was 13.7+/-24. No correlation was found between apoptosis and
      differentiation status of carcinoma. Bcl-2 expression was weakly detected in only
      one sample. P53 expression was detected in 26 of cases with mean staining index
      of 102+/-96. A significant correlation between p53 and Ki-67 staining indices was
      observed (r=0.521, p=0.001). Both p53 and Ki-67 expression showed a good
      association with the pathological grade (p=0.0001 and p=0.004, respectively).
      None of the markers showed significant correlation with AI and no correlation was
      found between the ratio of AI to PI and other parameters either. In conclusion,
      the frequency of apoptosis in TCC of bladder appears not to be associated with
      tumor grade, and with bcl-2, p53 and Ki-67 expression.

PMID- 15448752
TI  - Short term arterial remodelling in the aortae of cholesterol fed New Zealand
      white rabbits shown in vivo by high-resolution magnetic resonance imaging -
      implications for human pathology.
AB  - High-resolution, non-invasive imaging methods are required to monitor progression
      and regression of atherosclerotic plaques. We investigated the use of MRI to
      measure changes in plaque volume and vessel remodelling during progression and
      regression of atherosclerosis in New Zealand White rabbits. Atherosclerotic
      lesions were induced in the abdominal aorta by balloon injury and cholesterol
      feeding. MR images (2D) of the abdominal aorta were acquired with cardiac and
      respiratory gating using a fast spin echo sequence with and without fat
      suppression. In an initial study on rabbits treated for 30 weeks we imaged the
      aortae with a spatial resolution of 250x250 micrometers with a slice thickness of
      2 mm and achieved a close correlation between MRI-derived measurements and those
      made on perfusion pressure-fixed histological sections (r(1) = 0.83, slope p(1) <
      0.01). We subsequently imaged 18 rabbits before and periodically during 12 weeks
      of cholesterol feeding (progression) followed by 12 weeks on normal diet
      (regression). Aortic wall (atherosclerotic lesion) volume increased significantly
      during progression and decreased during regression. In contrast, lumen volume
      increased during progression and did not change during regression. In conclusion,
      this study confirms that non-invasive, high-resolution MRI can be used to monitor
      progression and regression of atherosclerosis, each within 3 months and shows,
      for the first time in a short-term model, that positive remodelling occurs early
      during progression and persists through regression of atherosclerotic lesions.

PMID- 15448753
TI  - Estrogen receptor expression in salivary gland mucoepidermoid carcinoma and
      adenoid cystic carcinoma.
AB  - Estrogen receptor (ER) expression in salivary gland carcinomas is controversial,
      and most published studies considered no more than 10 cases. We analyzed ER
      expression by immunohistochemistry in 136 mucoepidermoid carcinomas and 72
      adenoid cystic carcinomas. All cases were negative. These results do not support
      a role for estrogens in salivary gland mucoepidermoid carcinoma and adenoid
      cystic carcinoma.

PMID- 15448754
TI  - Renal cell cancer associated with sarcoid-like reaction.
AB  - An unusual granulomatous reaction within a conventional clear cell renal cancer
      in a 62 year-old woman is reported. Using immunohistochemical evaluation, cells
      of the granuloma were CD68 (Kp1), carboxypeptidase M and CD3 positive. No signs
      of sarcoidosis were found in other organs. According to the few publications that
      mention cancer associated sarcoid-like reaction, such lesions do not influence
      the prognosis. Our patient is still well for a 15 months follow-up.

PMID- 15448755
TI  - Ideal cooling process for paraffin-embedded tissues.
AB  - Back in the seventies everybody was convinced that it was no longer necessary to
      cool paraffinembedded tissues, because of the new advances in the production of
      paraffin. The reason for this assumption was the addition of plastic polymers and
      dimethyl sulfoxide. The quality of tissue sectioning improved because of these
      additives. The daily routine in the histology laboratories shows that it is
      impossible to produce good quality cutting without cooling. Cooling the paraffin
      by means of cooling plates or ice dishes creates drastic improvement; the cutting
      quality improves and it is much easier. Both improvements speed up the process
      and save time for the technicians and the physician. Long-term study indicates
      that not only the temperature but also the methodology of cooling and the cooling
      rate are playing a decisive role in the cutting quality.

PMID- 15448757
TI  - Risk factors of major noncommunicable diseases in Bahrain. The need for a
      surveillance system.
AB  - Noncommunicable diseases NCDs are the major cause of morbidity and mortality in
      Bahrain. The review examines the prevalence of risk factors of major NCDs from
      the available literature and determines the impact of the rapid socio economic
      changes on their burden. It further recommends ways of improving their reporting
      and monitoring. Smoking, obesity, diabetes, hypertension, hyperlipidemia,
      physical activity and nutrition are considered. The review points out that data
      on some of the factors is available but deficient for others. The call for the
      establishment of an integrated surveillance system using the World Health
      Organization STEPwise approach is stressed.

PMID- 15448758
TI  - Health hazards of cement dust.
AB  - Even in the 21st century, millions of people are working daily in a dusty
      environment. They are exposed to different types of health hazards such as fume,
      gases and dust, which are risk factors in developing occupational disease. Cement
      industry is involved in the development of structure of this advanced and modern
      world but generates dust during its production. Cement dust causes lung function
      impairment, chronic obstructive lung disease, restrictive lung disease,
      pneumoconiosis and carcinoma of the lungs, stomach and colon. Other studies have
      shown that cement dust may enter into the systemic circulation and thereby reach
      the essentially all the organs of body and affects the different tissues
      including heart, liver, spleen, bone, muscles and hairs and ultimately affecting
      their micro-structure and physiological performance. Most of the studies have
      been previously attempted to evaluate the effects of cement dust exposure on the
      basis of spirometry or radiology, or both. However, collective effort describing
      the general effects of cement dust on different organ and systems in humans or
      animals, or both has not been published. Therefore, the aim of this review is to
      gather the potential toxic effects of cement dust and to minimize the health
      risks in cement mill workers by providing them with information regarding the
      hazards of cement dust.

PMID- 15448756
TI  - Chondrosarcoma cell differentiation.
AB  - A mixed population of lymphocytes from a healthy donor co-existed with an
      established culture of allogeneic chondrosarcoma cells, during which time the
      tumor cells changed from malignantly transformed to benign fibroblast-like
      morphology; from multilayered to a monolayered growth pattern; lost their potency
      to grow in colonies in soft agar; and showed signs of senescence. A discussion of
      possible molecular mechanisms for this event is offered. If there are as yet
      undiscovered lymphokines that can induce reversal of the malignant
      geno/phenotype, the cognate gene(s) should be cloned for genetic engineering and
      for the mass production of the corresponding molecular mediators for clinical
      trials.

PMID- 15448759
TI  - Ethnic differences in hypertension and blood pressure control. Issues for
      prevention strategies.
AB  - Population studies revealed significantly lower levels of hypertension among
      rural community than both semi-urban and recently urbanized communities, and much
      of the difference was attributed to environmental factors. Migration studies
      revealed that increased sodium consumption is a key factor for the development of
      hypertension in some ethnic group, and people of African origin are known to be
      more prone to develop hypertension in western countries. Recent data obtained in
      European countries reveals that the rates of detection, treatment, and control
      are higher among the black population indicating a greater awareness among the
      general public and physicians in Europe of the importance of detecting and
      managing hypertension in blacks. However, due to the relevant role of the
      environment and increasing urbanization, the greater attention to prevention
      strategies should be placed in developing countries to prevent the onset of
      global epidemics. Primary prevention of hypertension is possible through weight
      reduction, regular exercise, salt restriction and other dietary measures, but in
      developing countries is specially important to identify groups where a particular
      intervention is more effective and to improve detection and control of
      hypertension.

PMID- 15448760
TI  - Coronary artery disease in Saudi Arabia.
AB  - OBJECTIVE: Coronary artery disease (CAD) is a major public health problem
      worldwide. To our knowledge, there is no national data available from community
      based studies on prevalence of CAD in the Kingdom of Saudi Arabia (KSA).
      Therefore, we designed this study with the objective to determine the prevalence
      of CAD among Saudis of both sexes, between the ages of 30-70-years in rural as
      well as urban communities. Further, to determine the prevalence and clinical
      pattern of the major modifiable risk factors for CAD among the same population.
      This work is part of a major national study on CAD in Saudis Study (CADISS).
      METHODS: This is a community based study conducted by examining subjects in the
      age group of 30-70-years of selected households during 5-year period between 1995
      and 2000 in KSA. Data were obtained from history using a validated questionnaire,
      and electrocardiography. The data were analyzed to provide prevalence of CAD and
      risk assessment model. RESULTS: Nine hundred and forty-four subjects, out of
      17232 were diagnosed to have CAD. Thus, the overall prevalence of CAD obtained
      from this study is 5.5% in KSA. The prevalence in males and females were 6.6% and
      4.4% (P<0.0001). Urban Saudis have a higher prevalence of 6.2% compared to rural
      Saudis of 4% (P<0.0001). The following variables are found to be statistically
      significant risk factors in KSA: age, male gender, body mass index (BMI),
      hypertension, current smoking, fasting blood glucose, fasting cholesterol and
      triglycerides. CONCLUSION: The overall prevalence of CAD in KSA is 5.5%. A
      national prevention program at community level as well as high risk groups should
      be implemented sooner to prevent the expected epidemic of CAD that we are seeing,
      beginning. Measures are needed to change lifestyle and to address the management
      of the metabolic syndrome, to reduce modifiable risk factors for CAD. A
      longitudinal study is needed to demonstrate the importance of reducing modifiable
      risk factors for CAD in KSA.

PMID- 15448761
TI  - Coronary stent thrombosis in bare metal stents.
AB  - OBJECTIVE: The incidence of coronary stent thrombosis has reduced with improved
      techniques and drugs. Nevertheless, clinical trials may not reflect real world
      practice due to the selective inclusion criteria, regional variations and more
      complex patients treated in day-to-day practice. We examined the frequency,
      predisposing factors and outcome of stent thrombosis in unselected patients
      undergoing bare metal stents. METHODS: All patients undergoing stent implantation
      are entered into a prospective database. We reviewed the incidence of stent
      thrombosis in our database for all patients with at least 6 months of follow up.
      RESULTS: From December 1996 through to December 2002, 1140 consecutive patients
      underwent a coronary stenting. Stent thrombosis occurred in 9 (0.8%) patients; 7
      (78%) presented within 30 days of the procedure, while 2 had late stent
      thrombosis occurring after 30 days. The vessel was left anterior descending
      artery in all, 8 (89%) had a recent anterior myocardial infarction prior to the
      intervention and the mean stent length was 25 mm. CONCLUSION: The incidence of
      stent thrombosis is approximately 1% in the current era of intervention. Longer
      stent length in the left anterior descending artery following a recent myocardial
      infarction, seems to be associated with stent thrombosis.

PMID- 15448762
TI  - Variations in the papillary muscles of normal tricuspid valve and their clinical
      relevance in medicolegal autopsies.
AB  - OBJECTIVE: In our study, tricuspid valves in cases of sudden death secondary to
      congenital differences of the tricuspid valve with significant papillary muscle
      anatomy were investigated. No studies of papillary muscle anatomy of the
      tricuspid valve have been found in medicolegal autopsies in literature. The
      purpose of our study is to investigate the relationship of papillary muscle in
      tricuspid valve in cases of sudden deaths, especially those resulting from
      cardiac disease, with the muscle structure, as well as the number of the muscle
      leading congenital changes. METHODS: The study was carried out in the Department
      of Anatomy, Faculty of Medicine, Ege, University, Izmir, Turkey and comprised of
      400 human hearts obtained between 2000 and 2002 from 400 autopsy cases during a
      medicolegal autopsy with permission from the Council of Forensic Medicine, Izmir.
      Quantitative and morphological aspects of the papillary muscles of the right
      ventricle were evaluated. The criteria such as number, incidence, length and
      shape of the anterior, (APM) septal (SPM) and posterior papillary muscles (PPM)
      have been observed. RESULTS: Although the papillary muscle presented great
      variability in numbers, with a minimum of 2 and a maximum of 9 papillary muscles
      in the right ventricle, there were usually 3 papillary muscles in the right
      ventricle; APM, PPM and SPM. The one headed APM was found to be more often in
      cardiac deaths. However, observing more frequent conical and flat topped
      configurations in all PPM was striking. The absence or lower ratio, or both of
      attachment bridges of SPM and APM/PPM in deaths of cardiac origin is also
      significant. We have found that the presence of this attachment is higher in
      deaths of noncardiac origin. CONCLUSION: This anatomical study may explain the
      increased in incidence wide variations of papillary muscle tricuspid valve in
      deaths of cardiac origin. The verdict in legal affairs may change with this. The
      knowledge regarding wide variations and minor anatomical abnormalities of
      papillary muscle helps forensic examiners not to get confused at unexpected
      deaths.

PMID- 15448763
TI  - Oxidative stress in chronic renal failure patients treated by peritoneal
      dialysis.
AB  - OBJECTIVE: To evaluate the role of oxidative stress (OS) in chronic renal failure
      (CRF) and the effect of peritoneal dialysis on the OS in uremic patients. Also,
      to investigate the role of the studied parameters of OS as early markers for the
      detection of peritonitis in peritoneally dialyzed patients. METHODS: The study
      was conducted on 80 chronic renal failure Iraqi patients who were admitted to the
      dialysis centers at Al-Kadhumiya, Baghdad, Al-Yarmouk and Al-Karama teaching
      hospitals, Baghdad, Iraq, during the period November 1999 through to July 2000
      for peritoneal or hemodialysis therapy. Their ages range between 15-75-years.
      This was carried out by measuring the plasma values of malondialdehyde (MDA),
      thiol group, albumin, uric acid and total bilirubin before and after the dialysis
      session, compared to age and sex matched healthy controls. RESULTS: The
      significantly higher plasma MDA with lower plasma thiol levels prior to the
      dialysis session indicated most likely an increased OS in CRF patients, which has
      significantly decreased after the dialysis session. This OS was found to be
      significantly correlated with the degree of renal insufficiency measured by serum
      creatinine levels. In patients who developed peritonitis, post dialysis findings
      were in favor of an increase rather than a decrease in OS. Such findings were
      found prior to the clinical or biochemical diagnosis of peritonitis or both in
      most patients. Finally, in patients on regular hemodialysis therapy, results
      suggested a minor OS compared to patients admitted for peritoneal dialysis
      therapy. CONCLUSION: Patients with CRF are subjected to an increased OS, the
      degree of which is related to the severity of renal failure. Moreover, plasma
      levels of the studied markers of OS do point in the direction of a decrease in
      the OS post dialysis. Such markers can be used for early detection of peritonitis
      in peritoneally dialyzed patients. Finally, chronic regular dialysis therapy is a
      more effective replacement therapy.

PMID- 15448764
TI  - Relationship between plasma angiotensinII, leptin and arterial blood pressure.
AB  - OBJECTIVE: Obesity and hypertension are 2 closely associated conditions and
      obesity probably predisposed to hypertension. The mechanism of the association
      between obesity and hypertension is not clear. The aim of the present study was
      to clarify the relationship between blood pressure (BP), body mass index (BMI),
      serum angiotensinII (AGII) and serum leptin levels and to investigate the
      relation between serum AGII and leptin. This study also aimed to rule out if
      there is a difference in serum AGII and leptin levels between lean and obese
      hypertensive females. METHODS: We measured fasting serum AGII and leptin levels
      in 16 normotensive lean (LN) females, 25 obese normotensive (ON) females, 12 lean
      hypertensive (LH) females and 25 obese hypertensive (OH) females. All subjects
      had no evidence of preexisting cardiovascular disease, were non pregnant, had no
      previous history of ill health or smoking and were not on antihypertensive
      therapy. This study was performed in King Abdul-Aziz University Hospital, Jeddah,
      Kingdom of Saudi Arabia from January 2002 through to January 2003 RESULTS: In
      lean groups, there were a significant increase in BMI and serum AGII in
      hypertensive group compared to normotensive group while the serum leptin level
      was insignificantly higher in hypertensive group than in normotensive group. On
      the other hand, there was a significant increase in serum AGII, BMI and serum
      leptin for obese hypertensive compared to obese normotensive group. The mean
      arterial blood pressure (ABP) was significantly correlated to serum AGII, serum
      leptin and BMI in all groups. A significant correlation was found between serum
      AGII and serum leptin if all studied females (LN, LH, ON and OH) or obese females
      (ON and OH) were analyzed (P=0.000 and 0.04). However, in lean females (LN and
      LH) there was no relation between serum AGII and serum leptin. CONCLUSION: When
      obesity is present, both serum AGII and serum leptin were strong predictor of BP,
      which is not the case in lean females in whom only serum AGII is a predictor of
      BP. Elevation of serum AGII and serum leptin levels when associated with
      increased BMI may contribute to the pathophysiology of obesity induced
      hypertension. Further study on leptin resistance in obese persons and its
      relation to increased ABP has to be carried out.

PMID- 15448765
TI  - Otitis externa infection in Jordan. Clinical and microbiological features.
AB  - OBJECTIVE: Aims of this study were to investigate the clinical findings and to
      identify causative microorganisms and their susceptibility to antibiotics in
      otitis externa infection. METHODS: The symptoms and signs, as well as the
      bacterial and fungal flora from the auditory canal of one hundred and eighty
      patients (100 males and 80 females), age range from 6 month to 19-years old
      suffering from acute otitis externa were studied from January 2001 to December
      2002. One way ANOVA and Least Significant Difference (LSD) were carried out for
      statistical analysis. RESULTS: Pain was the most common symptom (97.2%) while,
      itching and difficulty in hearing were the least common (11.7 %). Pseudomonas
      aeruginosa (P.aeruginosa) was isolated from (41.7%) which showed the best
      susceptibility to ciprofloxacin (93.4%), aspergillus species from (19.4%),
      candida albicans from (10.6%), staphylococcus aureus from (16.1%) which showed
      the best susceptibility to amikacin and ciprofloxacin (96.5%), proteus mirabilis
      from (2.8%) which showed the best susceptibility (100%) to amikacin,
      ciprofloxacin, imipenem and ofloxacin, anaerobic bacteria from (2.2%); and no
      bacteria growth was observed in (7.2%). There was a significant variation
      relating signs, symptoms and sex in favor of males (P=0.03). Significant seasonal
      variation in otitis externa infection was observed (P <0.05). CONCLUSION:
      Pseudomonas aeruginosa was the most frequently isolated pathogenic microorganism,
      which showed the best susceptibility to ciprofloxacin. Pain was the most common
      symptom.

PMID- 15448766
TI  - Cryptosporidiosis and other intestinal parasitic infections in patients with
      chronic diarrhea.
AB  - OBJECTIVE: To consider the relationship of the parasitic infections including
      cryptosporidium with chronic diarrhea. Also the effect of chronic disease as
      pulmonary tuberculosis (TB) and nosocomial infection on the occurrence rate of
      parasites in cases of chronic diarrhea. METHODS: Stool samples were collected
      from 205 patients in teaching, general, child and maternity hospitals in Basrah,
      Iraq, suffering from chronic diarrhea during 2000. Out of these patients, there
      were 40 patients with pulmonary TB and 50 inpatients with nosocomial infection.
      Also 175 apparently healthy individuals who have no episodes of diarrhea for at
      least 2-months were served as a control group. Direct smear method and then
      formalin ether sedimentation method were carried out for stool samples to detect
      intestinal parasites. Fecal smears were prepared from the sediment and stained by
      the modified Ziehl Neelsen stain for the recovery of red pink oocysts of
      cryptosporidium. RESULTS: Out of the 205 examined patients, cryptosporidium
      oocysts were found to be excreted in 20 (9.7%) patients in comparing to 1.1% of
      the control group. The difference is statistically significant. There were 109
      (53.2%) patients found to be positive for intestinal parasitic infections
      compared to 26 (14.8%) of the control group. The difference is also statistically
      significant. Out of the 40 TB patients, 2 (5%) were found to excrete
      cryptosporidium oocysts and also 27 (67.3%) were positive for intestinal
      parasites. In addition, there were 4 (8%) excreting cryptosporidium oocysts and
      23 (46%) infecting by intestinal parasites among the in patients with nosocomial
      infection. CONCLUSION: Both acid and non-acid fast parasites should be considered
      in the differential diagnosis of undiagnosed chronic diarrhea especially among
      patients with pulmonary TB or nosocomial infection.

PMID- 15448767
TI  - Implementation of the national asthma management guidelines in the emergency
      department.
AB  - OBJECTIVE: The national protocol for asthma management was released in 1995.
      There has been no national investigation to compare the actual care delivered at
      the Emergency Department to those recommended by these guidelines: To compare the
      documented management of acute bronchial asthma at the Emergency Room (ER) with
      the Saudi National Guidelines METHODS: Retrospective analyses of a total of 150
      ER records, of patients with a diagnosis of asthma over a one year period
      (January through to December 2000), at King Abdul-Aziz Medical City, King Fahad
      National Guard Hospital, Riyadh, Kingdom of Saudi Arabia. Documentation of the
      history, indices of severity, treatment given, pre-discharge assessment and
      prescriptions were compared to the nationally recommended management. RESULTS:
      History of the present attack, its duration, frequency of b-agonist use and
      nocturnal symptoms were documented in less than 50% of patients. Previous ER
      visits and hospitalization, peak flow rate and accessory muscle use were
      similarly recorded in less than 50% of patients whereas intensive care unit
      admission and intubation were documented in less than 15% of asthmatics. Steroids
      were given to only 46% of patients with acute asthma who visited the Emergency
      Department. Pre-discharge clinical assessment and peak flow readings were
      documented in 48% and 29%. Only 64% of patients were given a follow up
      appointment. CONCLUSION: The documented treatment of patients with an acute
      asthmatic episode at the ER varies significantly from what is recommended by the
      National and International Asthma Management Guidelines. Failure to implement
      Asthma Guidelines probably results in an inadequate care of asthmatic patients
      and raises the urgent need for a National Physician Asthma Education Program.

PMID- 15448768
TI  - The diagnostic value of C-reactive protein, white blood cell count and neutrophil
      percentage in childhood appendicitis.
AB  - OBJECTIVE: To analyze the value of C-reactive protein (CRP), total white blood
      cell count (WBC), and neutrophil percentage in the diagnosis of suspected cases
      of childhood appendicitis. METHODS: Prospective study of 216 patients admitted
      with a history of suspected acute appendicitis, between October 2001 through to
      May 2002, Al Fateh Teaching Hospital for Children, Benghazi, Libya. Blood samples
      for estimation of CRP, total WBC and neutrophil percentage were sent immediately
      to the laboratory. Sensitivity, specificity, positive predictive and negative
      predictive values were calculated, for each test and in combination. RESULTS:
      There were 139 male and 77 female patients, the age range was 3-13-years, 135
      patients were operated. Those who had appendicitis, we had 114 patients with
      positive CRP values of more than (8 microgram/ml), and 109 patients had total WBC
      count of more than (11,000/microL), and 111 patients with neutrophil percentage
      more of than 75%. One hundred and twelve patients out of 130 with appendicitis
      had the triple tests positive, and only 8 out of 86 patients without appendicitis
      had the triple tests positive. The sensitivity, specificity, positive and
      negative predictive values of the 3 tests in combination were 86%, 90.7%, 93%
      81.2%. CONCLUSION: Evaluation of the clinical symptoms and signs combined with
      the triple tests can improve the diagnostic accuracy and significantly reduce the
      incidence of perforation and the rate of negative laparotomy.

PMID- 15448769
TI  - The role of Helicobacter pylori in esophagitis and peptic ulcer disease in Iraq.
AB  - OBJECTIVE: The objectives of this study are to determine the prevalences of
      Helicobacter pylori (H.pylori) infection in symptomatic, but endoscopically
      normal patients as well as in patients with endoscopically and histologically
      proven esophagitis, gastritis, duodenitis, duodenal ulcer, and gastric ulcer.
      METHODS: The study extended over the period November 1999 through June 2000.
      Biopsy specimens were harvested from intact areas of gastric antral mucosa,
      duodenal bulb, gastric body and lower third of esophagus of each one of 200
      patients undergoing eseophago-gastro-duodenoscopy in endoscopy unit of Tikrit
      General Hospital (TGH), Salahuddin Governorate, Tikrit City, Iraq. The biopsies
      were submitted for histopathological, cultural and biochemical investigations.
      Seven biopsy samples were taken from each patient. Written consent was taken from
      each patient. The patients were pooled from various districts of the governorate.
      RESULTS: Helicobacter pylori was detected in antral biopsies of the following
      categories of patients: in 73.9% of patients with endoscopic gastritis, in 75% of
      patients with gastric ulcers, in 86% of patients with endoscopic duodenitis, in
      88.6% of patients with duodenal ulcers and in 57.7% of patients with endoscopic
      esophagitis, but absent in all patients with totally normal endoscopies.
      CONCLUSION: Although H.pylori has no role in the development of esophagitis, it
      is a prevalent pathogen and is associated with many gastro-intestinal diseases
      and has an important role in the pathogenesis of peptic ulcer disease and
      gastritis in our district.

PMID- 15448770
TI  - Indications and yield of upper gastrointestinal endoscopy in children.
AB  - OBJECTIVE: Knowledge of the pattern of gastrointestinal tract (GIT) disorders
      detected by endoscopy is important for clinicians. The objective of this paper is
      to report on the indications and yield of endoscopy. METHODS: Retrospective
      analysis of data of all patients below 18 years of age who underwent upper GIT
      endoscopy from 1414 H (1993 G) through to 1424 H (2002 G) over a 10-year period
      at King Khaled University Hospital, Riyadh, Kingdom of Saudi Arabia. RESULTS: One
      thousand and fifteen upper GIT endoscopies were performed, of which 851
      diagnostic procedures were performed on 851 children. The majority (96%) were
      Saudi nationals, the age range was between 4 days and 18-years, and the male to
      female ratio was 0.7: 1. The 2 most common indications were duodenal biopsy (29%)
      and abdominal pain (24%). The best diagnostic yield was in children presenting
      with ingestion of caustic substances, followed by hematemesis, and vomiting in
      86%, 75% and 67%. The overall yield, however, was 43%. Finally, the most common
      diagnoses were gastritis and esophagitis occurring in 32% and 30% of the
      children. Age related variations are reported. CONCLUSION: The increasing
      practice of endoscopy in children resulted in the development of new indications
      such as endoscopic small bowel biopsy. The differences in indications and yield
      of endoscopy with age reflecting the varying pattern of diseases.

PMID- 15448771
TI  - Cholesterolosis. Incidence, correlation with serum cholesterol level and the role
      of laparoscopic cholecystectomy.
AB  - OBJECTIVE: To report the incidence of cholesterolosis in the surgically removed
      gallbladders, its association with serum cholesterol level and to review the role
      of laparoscopic cholecystectomy in the treatment. METHODS: This retrospective
      study included all patients who had consecutive cholecystectomies for various
      gallbladder disorders, performed by 2 consultants during a 5-year period from
      January 1997 through to December 2002, in the College of Medicine and King Khalid
      University Hospital, King Saud University, Riyadh, Kingdom of Saudi Arabia. The
      clinical records of those found to have cholesterolosis on histopathological
      examination were reviewed, and the data were analyzed for their age, sex, fasting
      serum cholesterol level and the final outcome of cholecystectomy. RESULTS: The
      study group was comprised of 549 patients and out of which, 74 (13.4%) had
      cholesterolosis of the gallbladder. There were 59 (79.9%) female and 15 (20.1%)
      male patients. Age ranged from 18-64-years with a mean of 35.7-years. Sixty-three
      (85.1%) cases were reported to have abnormally high fasting serum cholesterol
      levels (>=5.5 mmol/L), whereas 11 (14.9%) had normal serum cholesterol level.
      Cholesterolosis with coexistent gallstones was documented in 47 (63.3%) patients
      while 27 (36.5%) subjects showed acalculous cholesterolosis. Laparoscopic
      cholecystectomy was performed in 71 (95.9%) individuals, whereas 3 patients ended
      up with open cholecystectomy (conversion rate of 4.2%). There were no
      postoperative complications. CONCLUSION: Cholesterolosis of the gallbladder is a
      distinct pathologic entity and carries a positive correlation with high serum
      cholesterol level. Laparoscopic cholecystectomy is effective, safe and a feasible
      treatment modality for cholesterolosis.

PMID- 15448772
TI  - Appraisal of the modified Alvarado Score for acute appendicits in adults.
AB  - OBJECTIVE: Decision making in cases of acute appendicitis may be difficult
      specially for junior surgeons. Radiological investigations do not appear to be
      helpful. In some studies, the Modified Alvarado Scoring System (MASS) was helpful
      in minimizing unnecessary appendicectomies. The aim this study was to evaluate
      the sensitivity of MASS in the diagnosis of acute appendicitis in adults.
      METHODS: All adult patients aged 16-years and above who were admitted with a
      provisional diagnosis of acute appendicitis between January 2001 and January
      2002, into the Armed Forces Hospitals, Southern Region, Khamis Mushayt, Kingdom
      of Saudi Arabia were prospectively entered into this study. The study included
      125 patients between the ages of 16 and 76-years. They were prospectively
      evaluated on admission using the Modified Alvarado Score (MAS) to determine
      whether or not they had acute appendicitis. The MASS was correlated with the
      operative and histopathological findings. RESULTS: One hundred and 10 patients
      (88%) had appendicectomies of which 30 patients (27.3%) had normal appendices on
      histopathology examination. Overall the MAS system showed a sensitivity of 53.8%
      and a specificity of 80%. For males, the sensitivity was 56.4% and the
      specificity was 100%. For females, the sensitivity and specificity were 48% and
      62.5%. CONCLUSION: From the results, the MASS is not sufficiently sensitive
      adopted as a method of diagnosing of acute appendicitis in adults in our
      environment. Further, requirements may be needed to improve its sensitivity and
      specificity.

PMID- 15448773
TI  - The influence of delay on perforation in childhood appendicitis. A retrospective
      analysis of 58 cases.
AB  - OBJECTIVE: Appendicitis is the most common non-traumatic surgical abdominal
      disorder in children aged 2-years or older. It is generally believed that delay
      in diagnosis and surgery of acute appendicitis is associated with a more advanced
      stage of disease and a higher morbidity. The aim of this retrospective study was
      to document the clinical features of acute appendicitis (AA), and to describe the
      factors associated with appendiceal perforation (AP) among children. METHODS:
      This study included 58 patients who underwent emergency appendectomy during the
      period January 1998 through to December 2002, Suleyman Demirel University
      Hospital, Isparta, Turkey. They were proven to have AA by operative findings and
      pathology reports, and were further included in this study. RESULTS: The
      preadmission delay which is mostly due to parents and post admission delay which
      is due to physicians other than pediatric surgeons were found as highly
      associative factors for AP. Perforation is unlikely in AA patients in the first
      48-hours of the abdominal pain. CONCLUSION: Associated symptoms of the abdominal
      pain may cause delay to diagnosis. The children who have abdominal pain and
      associated symptoms should be consulted with a pediatric surgeon.

PMID- 15448774
TI  - Risk factors predisposing to abruptio placentae. Maternal and fetal outcome.
AB  - OBJECTIVE: Abruptio placentae is one of the leading causes of perinatal deaths.
      Abruptio placentae increase the neonatal morbidity and mortality. It is one of
      the recognized causes of low birth weight. The purpose of this study was to
      examine the risk factors for abruptio placentae together with the maternal and
      fetal outcome in a large population based data set. METHODS: All cases of
      abruptio placentae presented to the Department of Obstetrics, Wad Medani Teaching
      Hospital, Sudan during the period January 1997 through to December 2002 were
      collected. All infants born to those cases were also collected and analyzed as
      live birth or stillbirth. The live born infants were followed for one month to
      detect the neonatal deaths. The study also aimed to determine the predisposing
      factors for abruptio placentae. The study was designed as a case control study
      from live, singleton births and singleton fetal death. RESULTS: The total number
      of abruptio placentae collected during this period was 1028, while the total
      number of births during the same period was 15620 giving and incidence of
      1028/15620 (6.5%) for abruptio placentae. The combined stillbirths and first
      month deaths were 20.2%. Abruptio placentae was associated with pre-eclampsia,
      diabetes, polyhydramnios and hypertension. Parity and maternal age were not
      associated with an increased incidence of abruption placentae. CONCLUSION: This
      study had the advantage of complete ascertainment of all reported cases of
      abruptio placentae during a period of 6-years. We found an increased risk for
      abruptio placentae associated with maternal diabetes, hypertension, pre-eclampsia
      and polyhydramnios. We found that infants born after abruptio placentae were
      small for gestational age and had lower Apgar scores than the control infants.
      The possibility of abruptio placentae should be considered by the clinician when
      managing pregnant women with any of those characteristics. Abruptio placentae
      should be managed in centers were there is advanced maternal and neonatal
      facilities.

PMID- 15448775
TI  - Impaired gestational glucose tolerance. Its effect on placental pathology.
AB  - OBJECTIVE: The aim of this study was to investigate several macroscopic and
      microscopic features of placenta in cases with impaired gestational glucose
      tolerance. METHODS: Seventy-five gm World Health Organization criteria for the
      diagnosis of gestational diabetes and impaired gestational glucose tolerance were
      followed during the period June 1999 through to June 2000, at the Maternity
      Hospital of Kuwait. Macroscopic and microscopic examinations of 95 placentas were
      carried out. Sixty-five were from the control patients and 30 were from cases
      with impaired gestational glucose tolerance. RESULTS: Mean maternal age, maternal
      weight and parity was significantly higher in the impaired gestational glucose
      tolerance (IGGT) group compared to the control group. Mean birth weight of the
      baby was significantly higher in the IGGT group compared to the control group.
      Mean placental weight and the percentage of the cesarean delivery was higher in
      the IGGT group but did not reach the level of significance. There was no
      significant association between the microscopic features of the placenta in the
      control and IGGT groups. CONCLUSION: Impaired gestational glucose tolerance is
      related to increased neonatal and placental weight, which may lead to a higher
      number of cesarean deliveries, stressing the similarity between impaired
      gestational glucose tolerance and gestational diabetes mellitus. More stringent
      criteria may be necessary to define gestational diabetes. Microscopic features of
      placenta both in the control and IGGT groups did not show any significant
      difference.

PMID- 15448776
TI  - Lifestyle related risk factors for breast cancer in Jordanian females.
AB  - OBJECTIVE: To compare the lifestyle related risk factors for breast cancer such
      as physical activity, cigarette smoking, the use of contraceptive pills and
      increased body weight between non-familial and familial breast cancer females in
      Jordan. METHODS: This study was carried out in the Kingdom of Jordan during the
      period 2000 through to 2002. A questionnaire was used to collect information from
      99 females who were histologically and pathologically diagnosed for breast
      cancer. Data of the questionnaire was entered and analyzed using statistical
      package for social sciences. RESULTS: This study showed no significant difference
      between familial, non-familial breast cancer females and controls in the
      following risk factors: physical activity, contraceptive methods, and smoking. On
      the other hand, a statistically significant difference in weight was found
      between the familial breast cancer females, the total breast cancer females and
      the controls. In addition, the highest percentage of overweight and obese was
      found among postmenopausal breast cancer females. CONCLUSION: Postmenopausal
      obesity is a significant risk factor among Jordanian breast cancer females.

PMID- 15448777
TI  - Growth centiles for Omani premature infants born at 26 weeks of gestation.
AB  - OBJECTIVE: The present growth chart used in the Sultanate of Oman does not
      contain centile measurements for infants born at 26-weeks of gestation. With the
      increased survival of these premature infants, there is a growing need to develop
      such a chart. The present study was conducted with the aim to look at the
      anthropometric measurements (weight, length and head circumference) of Omani
      premature infants born at 26-weeks of gestation and to develop centile charts for
      these measurements. METHODS: The study was conducted at the Special Care Baby
      Unit (SCBU) of the Royal Hospital, one of the major perinatal institutions in
      Muscat, Oman. A computerized database is maintained for all the admissions from
      1996. We extracted the required anthropometric data for all 26-week gestation
      premature Omani infants admitted to SCBU from January 1996 to November 2003. A
      total of 49 babies were admitted during that period. Out of these, 43 had
      complete information on the growth parameters, including birth weight, length and
      head circumference. These parameters were noted down and by using the statistical
      package, an analysis was performed to get the normal distribution curve. By using
      the Microsoft Excel program, graphs were generated for all the 3 growth
      parameters. RESULTS: The mean birth weight for the premature infants born at 26
      week gestation was noted to be 908 +/- 156 grams, with length and head
      circumference of 33.5 +/- 2.5 and 24.5 +/- 1.7 centimeters. The normal
      distribution curve was obtained with minimal skewing. CONCLUSION: We were able to
      generate centile charts of the anthropometric measurements for Omani infants born
      at 26-weeks of gestation. The next step is to collect the national data from
      other institutions in Oman and then incorporate it into the present growth chart
      to make the charts more valid, reliable and applicable.

PMID- 15448778
TI  - Ocular pseudoexfoliation associated with hearing loss.
AB  - OBJECTIVE: Ocular pseudoexfoliation (PXF) has been recently considered as a
      systemic disease affecting other organs as well as the eye. This prospective
      study is to assess the relationship between PXF and sensorineural hearing loss.
      METHODS: Patients attending a general ophthalmic clinic at King Hussein Medical
      Center, Amman, Jordan from (March 2002 through to March 2003) who were found to
      have ocular PXF on routine ophthalmic examination were referred to the
      Audiometric Department. Pure tone hearing threshold was measured at 1, 2, 3 kHz
      for each ear and was compared with International Standard (ISO 7029) median age
      associated hearing loss at 1, 2, 3 kHz (AAHL). RESULTS: Forty-one patients were
      studied of whom 24 were males (58.5%); the mean age of the male patients was 78
      years while that of the female group was 72-years. All patients had PXF affecting
      at least one eye, 16 patients (39%) had bilateral PXF. Overall (72-years) of 36
      patients (87%) had a higher hearing threshold level (HTL) at 1, 2, 3 kHz (HTL (1,
      2, 3) than the ISO 7029 median AAHL 1, 2, 3 which included (44 ears) of 22
      patients in the male group (87%) and (28 ears) of 14 patients in the female group
      82%. Approximately 26.8% of patients had glaucoma, however; there was no
      correlation between glaucoma and sensorineural hearing threshold level.
      CONCLUSION: The majority of patients with ocular PXF had sensorineural hearing
      loss compared to age-matched controls. Thus, there is increasing evidence that
      PXF is a systemic disease.

PMID- 15448779
TI  - Treating heparin-induced thrombocytopenia. The unconventional way!
AB  - Heparin-induced thrombocytopenia HIT is a potentially devastating complication of
      heparin therapy. The severe form of HIT has been associated with both venous and
      arterial thrombosis manifested by myocardial infarction, cerebrovascular
      occlusion, skin necrosis or limb ischemia. Several agents are now available as
      alternatives to heparin in patients with suspected HIT, including the thrombin
      specific inhibitors lepirudin and argatroban as well as the low molecular weight
      heparinoid known as danaparoid. When lacking these agents, here we report the use
      of plasmapheresis to create an artificial state of anticoagulation; exchanging
      patient's plasma with albumin rather than fresh frozen plasma, to allow the safe
      introduction of warfarin.

PMID- 15448780
TI  - Multiple enchondromatosis Ollier's disease with two primary brain tumors.
AB  - A rare case of multiple enchondromatosis associated with 2 primary brain tumors
      is reported. A 21-year-old female who has diagnosed as Ollier's disease at the
      age of 9-years was admitted to the hospital with complaint of diplopia and
      progressive right upper and lower limb weakness. Magnetic resonance imaging of
      the brain depicted 2 intra-axial mass lesions. Stereotactic biopsy showed low
      grade fibrillary astrocytoma in both lesions. This report emphasizes that
      patients with Ollier's disease are at a higher risk for primary brain tumors than
      has been previously recognized.

PMID- 15448781
TI  - Unusual location of eosinophilic granuloma.
AB  - Eosinophilic granuloma EG is a well-recognized benign form of Langerhans cell
      histiocytosis, most commonly involving the skull bones. In this paper, we report
      an 8-year-old girl with EG of posterior element of vertebra; she had complete
      resolution with surgical curettage and bone grafting.

PMID- 15448782
TI  - Pleural flap for delayed presentation of intrathoracic esophageal perforation.
AB  - The authors report 2 cases of large intrathoracic esophageal perforation, as a
      complication of foreign body in 2 boys, 4 and 9-years-old. The delay in diagnosis
      was more than 36 hours in both cases that were treated successfully by a large
      pleural flap. Postoperatively, solid oral feeding was initiated after 2 weeks.
      Although gastrostomy was not performed on both patients, in cases of large
      esophageal perforation, it is recommended to establish early feeding and prevent
      aggressive vomiting.

PMID- 15448783
TI  - Ovarian mucinous cystadenoma in a female with Turner syndrome.
AB  - The development of an epithelial tumor, especially mucinous type, in a female
      with a streak gonad is rare and not fully understood. We report a case of a 19
      year-old; a single female known to have Turner syndrome presented with an
      increased abdominal girth and was found to have a huge pelvic and abdominal mass.
      Ultrasound and magnetic resonance imaging revealed a huge cystic ovarian mass
      with no ascites. Laparotomy and right oophorectomy were performed for the ovarian
      mass. Histology revealed a large mucinous cyst adenoma. Further study of these
      tumors may help to eludicate the underlying cause and pathogenesis.

PMID- 15448784
TI  - Cushing's syndrome. Case illustration and guidelines in management.

PMID- 15448785
TI  - Cavitation of mesenteric lymph nodes without celiac disease.

PMID- 15448786
TI  - The practice of do-not-resuscitate orders in the Kingdom of Saudi Arabia. The
      experience of a tertiary care center.

PMID- 15448787
TI  - The first Arabic health related quality of life visual function assessment tool.
      The Arabic visual function tool AVFT.

PMID- 15448788
TI  - Prevalence of the anatomic variations of the extra biliary ducts in Khartoum,
      Sudan.

PMID- 15448789
TI  - Tracheostomy in pediatric intensive care. Analysis of 5-year-experience and
      review of literature.

PMID- 15448790
TI  - Pattern of gastroenterology psychiatric consultations. A prospective study.

PMID- 15448791
TI  - Incidence and patterns of bone marrow involvement in Ewing's sarcoma.

PMID- 15448792
TI  - Challenges in creating the educated surgeon in the 21st century. Where do we
      stand?

PMID- 15448793
TI  - Terminology in diabetes; an example of resistance to change.

PMID- 15448794
TI  - A survey of patients' attitude toward total knee replacement in a major center in
      the Kingdom of Saudi Arabia.

PMID- 15448795
TI  - Congenital adrenal hyperplasia due to 3 beta-hydroxysteroid dehydrogenase type II
      deficiency in 4 Saudi children. Long term follow up.

PMID- 15448796
TI  - Risk factors for recurrent miscarriage in Sudanese women.

PMID- 15448797
TI  - The relationship between intrapartum amniotic fluid index, fetal distress and
      fetal acidemia.

PMID- 15448798
TI  - Quinolone resistance in non-typhoidal Salmonellae isolated from patients having
      primary extra-intestinal infections.

PMID- 15448799
TI  - Hemodialysis and ultrafiltration. A bridge to cardiac surgery.

PMID- 15448800
TI  - Extrapyramidal syndrome after treatment of falciparum malaria with sulphadoxine
      pyrimethamine.

PMID- 15448801
TI  - Antimicrobial resistance of Gram-negative bacilli from an intensive care unit in
      Trinidad, West Indies.

PMID- 15448802
TI  - Predictors of neonatal mortality in the intensive care unit in Abha, Kingdom of
      Saudi Arabia.

PMID- 15448803
TI  - Brazil is getting older: some lessons from the Bambui Health and Aging Study.

PMID- 15448804
TI  - Surgery or general medicine--a study of the reasons underlying the choice of
      medical specialty.
AB  - CONTEXT: The reality of medical services in Brazil points towards expansion and
      diversification of medical knowledge. However, there are few Brazilian studies on
      choosing a medical specialty. OBJECTIVE: To investigate and characterize the
      process of choosing the medical specialty among Brazilian resident doctors, with
      a comparison of the choice between general medicine and surgery. TYPE OF STUDY:
      Stratified survey. SETTING: Hospital das Clinicas, Faculdade de Medicina,
      Universidade de Sao Paulo (HC-FMUSP). METHODS: A randomized sample of resident
      doctors in general medicine (30) and surgery (30) was interviewed. Data on
      sociodemographic characteristics and the moment, stability and reasons for the
      choice of specialty were obtained. RESULTS: The moment of choice between the two
      specialties differed. Surgeons (30%) choose the specialty earlier, while general
      doctors decided progressively, mainly during the internship (43%). Most residents
      in both fields (73% general medicine, 70% surgery) said they had considered
      another specialty before the current choice. The main reasons for general
      doctors' choice were contact with patients (50%), intellectual activities (30%)
      and knowledge of the field (27%). For surgeons the main reasons were practical
      intervention (43%), manual activities (43%) and the results obtained (40%).
      Personality was important in the choice for 20% of general doctors and for 27% of
      surgeons. DISCUSSION: The reasons found for the choice between general medicine
      and surgery were consistent with the literature. The concepts of wanting to be a
      general doctor or a surgeon are similar throughout the world. Personality
      characteristics were an important influencing factor for all residents, without
      statistical difference between the specialties, as was lifestyle. Remuneration
      did not appear as a determinant. CONCLUSION: The results from this group of
      Brazilian resident doctors corroborated data on choosing a medical specialty from
      other countries with different social and educational characteristics. This
      congruence indicates that the choice involves very similar desires and needs in
      different settings and has little dependence on the students' educational
      context.

PMID- 15448805
TI  - Demographic and clinical characteristics of hypertensive patients in the internal
      medicine outpatient clinic of a university hospital in Rio de Janeiro.
AB  - CONTEXT: Hypertension is one of the most important cardiovascular risk factors
      but its control is still a challenge for physicians all around the world. For
      blood pressure control to be improved, it is important to guarantee the quality
      of attendance provided for hypertensive patients, especially in teaching
      hospitals, where future physicians are being trained. OBJECTIVE: To characterize
      the profile of hypertensive patients attending the internal medicine outpatient
      clinic of a university hospital in Rio de Janeiro,describing their cardiovascular
      risk and identifying flaws in the treatment provided for severely hypertensive
      patients, in order to implement an arterial hypertension management program. TYPE
      OF STUDY: A descriptive cross-sectional population-based study. SETTING: Hospital
      Universitario Clementino Fraga Filho, Universidade Federal do Rio de Janeiro.
      METHODS: The study was carried out over a period of four months, involving all
      the hypertensive patients under treatment in the outpatient unit. The attending
      physician obtained information relating to demographic features, cardiovascular
      risk factors, target organ damage, blood pressure levels, therapeutic regimens
      and compliance with treatment. Means and the respective standard deviations and
      proportions were used to describe the distribution of patient data. RESULTS: Of
      the total number of patients seen, 24.2% (1,699 patients) were hypertensive.
      Women accounted for 65.0% of the patients. The mean age was 63.9 years.
      Dyslipidemia (49.2%) and diabetes (29.8%) were the most frequently reported risk
      factors and heart disease was the most prevalent end-organ damage. Seventy
      percent of the patients were classified as high cardiovascular risk. In spite of
      the high intensity treatment provided for the most severe patients (19.4% on a
      regimen of 3 or more antihypertensive drugs), the rate of blood pressure control
      was low (27%). CONCLUSIONS: The patients with arterial hypertension under
      treatment at the university hospital had a profile of high cardiovascular risk
      and poor blood pressure control. Greater effort for improving hypertension
      control is needed, since this is the only way to reduce the morbidity and
      mortality rates of cardiovascular diseases.

PMID- 15448806
TI  - Obstetric and perinatal effects of active and/or passive smoking during
      pregnancy.
AB  - CONTEXT: Cigarette smoke, whether inhaled voluntarily or not, causes damage to
      the mother-infant pair. The antenatal period may present the best opportunity for
      performing effective anti-smoking campaigns. OBJECTIVE: To study the obstetric
      and perinatal effects of smoking on pregnancy and the infant. TYPE OF STUDY:
      Prospective study, interviewing pregnant women who were randomly selected at the
      maternity hospital as they were being discharged after giving birth. SETTING:
      Hospital Municipal Vereador Jose Storopolli, Sao Paulo, Brazil. METHODS: 758
      patients were interviewed regarding smoke inhalation before being discharged from
      the maternity hospital. The groups were formed by 42 active smokers, 272 passive
      smokers, 108 who inhaled smoke both actively and passively, and 336 non-smokers.
      The groups were compared regarding age, parity, school education, incidence of
      spontaneous abortion, rate of caesarian births, average gestational age at birth,
      rate of low birth weight and adequacy of weight in relation to the gestational
      age of newborn infants. For all variables we considered p < 0.05 as statistically
      significant. RESULTS: There was a high rate (55.7%) of pregnant smokers,
      including 5.5% active, 35.9% passive and 14.3% active-passive smokers. Active and
      active-passive smokers were older and had higher parity. Active smokers had lower
      education levels and higher rates of previous spontaneous abortion. The weights
      of newborn babies were lower for smoking mothers. DISCUSSION: The study was
      performed among patients that were mostly of low economic, social and cultural
      levels, thus possibly explaining the high incidence of smokers. Worse still was
      that 35.9% of the non-smokers were actually passive smokers. These rates we
      report were similar to those from the literature. The typical receptiveness of
      teenage girls to unrestricted advertising in the media contributes towards an
      early start to acquiring the habit of smoking, including during pregnancy in our
      country. We emphasize the difficulties in quantifying exposure to cigarettes even
      among active smokers. CONCLUSIONS: Cigarette smoke, whether inhaled voluntarily
      or not, has an unfavorable effect on the mother-infant pair.

PMID- 15448807
TI  - Bilirubin dosage in cord blood: could it predict neonatal hyperbilirubinemia?
AB  - CONTEXT: With early discharge, many newborns have to be readmitted to hospital
      for hyperbilirubinemia to be treated, and this has been held responsible for the
      reappearance of kernicterus. OBJECTIVE: To evaluate whether bilirubin levels in
      cord blood could predict neonatal hyperbilirubinemia that would require
      treatment, in full-term newborns up to their third day of life. TYPE OF STUDY:
      Prospective study. SETTING: Neonatal Unit of Hospital Israelita Albert Einstein,
      Sao Paulo, Brazil. PARTICIPANTS: 380 full-term newborns considered normal: with
      or without ABO/Rh blood group incompatibility and without other complications.
      PROCEDURES: Blood was taken from the umbilical cord for analysis of conjugated,
      unconjugated and total bilirubin serum levels. The newborns were followed up
      until discharge, and unconjugated bilirubin that required phototherapy was
      compared to the cord bilirubin assay. Discriminant analysis was used to classify
      newborns: with or without risk of needing phototherapy by the third day of life.
      MAIN MEASUREMENTS: Bilirubin assay in cord blood; mother's and newborn's blood
      groups; phototherapy indication. RESULTS: The mean value for unconjugated
      bilirubin in cord blood was significantly higher in newborns whose unconjugated
      bilirubin required phototherapy. The presence of ABO blood group incompatibility
      was a significant variable in relation to unconjugated bilirubin that required
      phototherapy. The most useful cutoff point for unconjugated bilirubin in cord
      blood was 2.0 mg/100 ml. DISCUSSION: Cord blood could be collected, stored and
      used for further analysis of unconjugated bilirubin levels as a means for
      considering whether or not to discharge a moderately jaundiced child from
      hospital, in association with other resources. CONCLUSIONS: Blood incompatibility
      between mother and child was a predictor for the appearance of hyperbilirubinemia
      that required treatment. Considering a cutoff point of 2.0 mg/100 ml, it could be
      concluded that 53% of the newborns who had greater unconjugated bilirubin levels
      in cord blood would reach levels requiring phototherapy by the third day of life.

PMID- 15448808
TI  - The role of electron microscopy for the diagnosis of glomerulopathies.
AB  - CONTEXT: Electron microscopy has been used for the morphological diagnosis of
      glomerular diseases for more than three decades and its value has been widely
      emphasized. However, recent reports have analyzed the routine use of electron
      microscopy critically. Its use in other areas of diagnosis such as tumor diseases
      has declined considerably; in addition, in view of the unavoidable financial
      pressure for the reduction of costs due to investigations and diagnostic
      routines, the selection of cases for electron microscopy has been quite rigorous.
      OBJECTIVE: To identify the glomerular diseases that depend on electron microscopy
      for a final diagnosis, by means of reviewing renal biopsies performed over a 12
      year period. DESIGN: Prospective SETTING: Hospital Ana Costa, Hospital Guilherme
      Alvaro and Servico de Anatomia Patologica de Santos, Santos, Sao Paulo, Brazil.
      PARTICIPANTS: 200 consecutive renal biopsies obtained from private hospitals and
      the teaching hospital from 1979 to 1991 were studied. MAIN MEASUREMENTS: All
      cases were analyzed via light microscopy, immunofluorescence and electron
      microscopy. The diagnosis was first made via light microscopy plus
      immunofluorescence and then via electron microscopy. RESULTS: Electron microscopy
      was diagnostic or essential for diagnosis in 10.0% of the cases, corresponding to
      3.4% of primary glomerulopathies and 100% of hereditary glomerulopathies.
      Electron microscopy was contributory (useful) to the diagnosis in 5.5% of the
      cases, confirming the preliminary diagnosis formulated on the basis of clinical
      and laboratory data and light microscopy plus immunofluorescence findings. We
      obtained a 7.5% rate of discordant immunofluorescence, which was considered as
      such when negative immunofluorescence findings were not confirmed by electron
      microscopy. The final diagnosis with the use of light microscopy plus
      immunofluorescence alone was 77.0%. CONCLUSIONS: It was possible to diagnose with
      certainty a great percentage of glomerulopathies (82.5-90% of the cases) based on
      the light microscopy and immunofluorescence findings alone. Electron microscopy
      was essential for the diagnosis of hereditary nephropathies.

PMID- 15448809
TI  - Possible hepatotoxicity of chronic marijuana usage.
AB  - CONTEXT: Hepatotoxicity is a potential complication from the usage of various
      illicit drugs, possibly consequent to their liver metabolism, but information on
      this is scarce in the medical literature. OBJECTIVE: To study the occurrence of
      clinical and laboratory hepatic alterations in chronic marijuana users, from the
      use of marijuana on its own or in association with other legal or illicit drugs.
      TYPE OF STUDY: transversal study SETTING: Hospital Espirita de Marilia, Marilia,
      Sao Paulo, Brazil PARTICIPANTS: The study was made among 123 patients interned in
      the Hospital Espirita de Marilia from October 1996 to December 1998, divided into
      3 groups: 26 (21%) using only marijuana, 83 (67.5%) using marijuana and crack,
      and 14 (11.4%) consuming marijuana and alcohol. PROCEDURES AND MAIN MEASUREMENTS:
      Patients were examined clinically with special emphasis on types of drugs used,
      drug intake route, age when consumption began, length and pattern of usage,
      presence of tattooing, jaundice, hepatomegaly and splenomegaly. Serum
      determinations of total proteins, albumin, globulin, total and fractions of
      bilirubin, aspartate (AST) and alanine (ALT) aminotransferases, alkaline
      phosphatase (AP), gamma-glutamyltransferase and prothrombin activity were
      performed. RESULTS: Among users of only marijuana, hepatomegaly was observed in
      57.7% and splenomegaly in 73.1%, and slightly elevated AST (42.3%), ALT (34.6%)
      and AP (53.8%). The three groups did not differ significantly in the prevalence
      of hepatomegaly, splenomegaly and hepatosplenomegaly. The group using both
      marijuana and alcohol showed the highest prevalence of alterations and highest
      levels of aminotransferases. Mean AP levels were above normal in all groups.
      CONCLUSIONS: Chronic marijuana usage, on its own or in association with other
      drugs, was associated with hepatic morphologic and enzymatic alterations. This
      indicates that cannabinoids are possible hepatotoxic substances.

PMID- 15448810
TI  - Determinants of impaired growth among hospitalized children: a case-control
      study.
AB  - CONTEXT: Protein energy malnutrition constitutes a public health problem,
      especially in less affluent countries. The identification of amenable predictive
      risk factors is of major importance for policy makers to plan interventions to
      reduce infant malnutrition. OBJECTIVE: To identify risk factors for protein
      energy malnutrition among hospitalized low-income children aged 6 to 24 months.
      TYPE OF STUDY: Case-control study. SETTING: Two public hospitals in Recife,
      Brazil. PARTICIPANTS: The cases were 124 infants with length-for-age below the
      10th percentile of the National Center for Health Statistics curve and the
      controls were 241 infants with length-for-age equal to or above the 10th
      percentile who were recruited in the same infirmary. METHODS: Cases and controls
      were compared in relation to a variety of sociodemographic, environmental and
      reproductive factors, and their healthcare, previous feeding practice and
      morbidity. Logistic regression analysis was used to investigate the net effect of
      risk factors on infant malnutrition, after adjusting for potential confounding
      variables. RESULTS: The mother's age, possession of a TV set, type of water
      supply, family size and location of the home were significantly associated with
      child malnutrition in the bivariate analysis. However, these associations lost
      their significance after adjusting for other explanatory variables in the
      hierarchical logistic regression analysis. This analysis showed that low birth
      weight contributed the largest risk for impaired growth. Increased risks of
      infant malnutrition were also significantly associated with households that had
      no toilet facilities or refrigerator, high parity for the mother, no
      breastfeeding of the infant, inadequate vaccination coverage and previous
      hospitalization for diarrhea and pneumonia. DISCUSSION: The literature shows that
      chronic malnutrition, as assessed by low length-for-age indexes, is often related
      to low income. However, this was not the case in this study, in which other
      variables had greater impact on child growth. CONCLUSIONS: In view of the
      multiple causes of malnutrition, the interrelationship among its determinants
      should be taken into account when adopting strategies for its reduction and
      prevention.

PMID- 15448811
TI  - The role of HER2/neu, BCL2, p53 genes and proliferating cell nuclear protein as
      molecular prognostic parameters in localized prostate carcinoma.
AB  - CONTEXT: Prostate cancer is the most frequent solid genitourinary neoplasm in
      men. Involvement of several genes has been described in the promotion and
      progression of prostate carcinoma. OBJECTIVE: To study the expression of the
      oncogenes HER2/neu and BCL2, tumor suppressor gene p53 and the tumor
      proliferation rate in 150 radical prostatectomy specimens, in order to define
      their role as prognostic parameters in localized prostate cancer. TYPE OF STUDY:
      Prospective study. SETTING: Universidade Federal de Sao Paulo and Hospital Sirio
      Libanes, Sao Paulo PARTICIPANTS: One hundred and fifty men who were submitted to
      radical prostatectomy between August 1997 and August 1998, for localized prostate
      cancer. MAIN MEASUREMENTS: All specimens underwent evaluation in their entirety,
      to determine tumor volume percentage, tumor extent and Gleason score.
      Immunohistochemistry was performed to determine gene expression using anti-
      HER2/neu, BCL2 and p53 antibodies, and proliferating cell nuclear antigen. The
      chi-squared test was used for correlation between gene expression, proliferative
      activity and histological variables. RESULTS: Thirty percent of the cases were
      p53 positive. There was positive correlation between p53 expression and tumor
      stage. The p53 expression was 22.9% and 42.6% for pT2 and pT3 tumors,
      respectively (p = 0.01). Expression of HER2/neu, BCL2 and proliferating cell
      nuclear antigen was identified in 66%, 23% and 43% of patients, respectively.
      There was no correlation between these three parameters and tumor volume, Gleason
      score or tumor stage. CONCLUSION: One-third of prostate adenocarcinomas express
      p53 protein, and this characteristic is related to tumor stage. HER2/neu is
      frequently expressed in prostate carcinomas, with no correlation with
      histological parameters. BCL2 is rarely expressed, and together with
      proliferative activity has no relationship with prognostic pathological variables
      in these neoplasms.

PMID- 15448812
TI  - Gefitinib (Iressa) in metastatic patients with non-small cell lung cancer:
      preliminary experience in a Brazilian center.
AB  - CONTEXT: Patients with metastatic non-small cell lung cancer are deemed
      incurable, but they may derive some benefit from systemic palliative
      chemotherapy. Recently, with the introduction of epidermal growth factor receptor
      (EGFR) antagonists such as gefitinib (Iressa), an effective and less toxic option
      is now available for the treatment of such patients. OBJECTIVE: To assess the
      activity and toxicity of gefitinib in a group of Brazilian patients. TYPE OF
      STUDY: Prospective, open label, non-randomized and non-controlled. SETTING:
      Clinica de Oncologia e Hematologia (CLIOH), Sao Paulo, Brazil. PATIENTS AND
      METHODS: From June 2002 to April 2003 we treated five patients with metastatic
      previously-treated non-small cell lung cancer (median of two previous
      chemotherapy regimens), using gefitinib at a dose of 250 mg orally on a daily
      basis, within a compassionate protocol sponsored by AstraZeneca. The patients'
      median age was 65 years and two of them were male. Three had a performance status
      of 1, one of 2 and one of 3, on the ECOG (Eastern Cooperative Oncology Group)
      scale. RESULTS: We observed skin rash in two patients, diarrhea in three and
      arthralgia in two. One patient had a partial response and another had
      stabilization of her disease, as measured via imaging studies (which have lasted
      for more than 11 and 4 months, respectively), which were accompanied by
      significant decrease in tumor markers, whereas three patients worsened during
      treatment. DISCUSSION: New options of chemotherapy agents with favorable toxicity
      profiles are urgently needed for the treatment of metastatic non-small lung
      cancer patients who usually have short life expectancies. In our small series of
      five patients, we observed stabilization of the disease in two of them and the
      skin and gastrointestinal reactions often described in the literature in all of
      them. Two had arthralgia, not reported before. CONCLUSION: We concluded that
      gefitinib is an important addition to the therapeutic armamentarium for patients
      with metastatic non-small cell lung cancer.

PMID- 15448813
TI  - Multiple lymphomatous polyposis of the gastrointestinal tract.
AB  - CONTEXT: Gastrointestinal multiple lymphomatous polyposis is a rare type of
      malignant lymphoma that has aggressive biological behavior, early systemic
      dissemination and poor prognosis. It is considered to be a manifestation of non
      Hodgkin lymphoma and represents the gastrointestinal counterpart of mantle cell
      nodal lymphoma. OBJECTIVE: A case of gastrointestinal multiple lymphomatous
      polyposis is presented and the anatomopathological, clinical, diagnostic and
      treatment aspects of this unusual neoplasia are discussed. CASE REPORT: The
      patient was a 59-year-old white male with a complaint of asthenia, night
      sweating, alteration in intestinal habit and weight loss over the preceding two
      months. The physical examination showed pallid mucosa and a palpable mass in the
      epigastrium and mesogastrium. Endoscopy of the upper digestive tract showed the
      presence of gastric and duodenal polyps. An opaque enema showed multiple polypoid
      lesions, especially in the cecum. A rectal biopsy revealed infiltration of the
      mucosa and submucosa by diffuse lymphoma consisting of small cleaved cells.
      Immunohistochemical study showed lymphocytes that expressed the antibody CD20 (L
      26) and light-chain kappa (k) immunoglobulin, but not light-chain lambda (l)
      immunoglobulin. The patient presented a condition of acute intestinal obstruction
      with the presence of a mesenteric mass formed by agglutinated lymph nodes that
      surrounded the proximal ileum, thereby obstructing its lumen. He was submitted to
      a segmental enterectomy and gastrotomy with excisional biopsies of the gastric
      polypoid lesions. After two cycles of chemotherapy there was a worsening of the
      general state, with an increase in the dimensions of the abdominal masses and
      sepsis, accompanied by progressive respiratory insufficiency, leading to death.

PMID- 15448814
TI  - Central retinal vein prethrombosis as an initial manifestation of protein S
      deficiency.
AB  - CONTEXT: Retinal vein thrombosis is most common in old people, and is often
      associated with systemic vascular disease. One of its rare systemic causes is
      protein S deficiency. CASE REPORT: A case of a 21-year-old woman with retinal
      vein prethrombosis associated only with protein S deficiency is described. She
      presented with acutely reduced visual acuity and a central scotoma in her left
      eye. Warfarin therapy was initiated, and complete improvement in ophthalmoscopic
      findings was subsequently observed. This case illustrates that protein S
      deficiency is a factor that should be considered in cases of retinal vein
      occlusion, particularly in young patients.

PMID- 15448816
TI  - [Growth, diarrhea, and breastfeeding: the case of Vila do Joao].
AB  - A prospective study on children under six months old living in an urban area on
      the periphery of Rio de Janeiro was carried out to examine the possible effect of
      diarrhea in differentiating the monthly growth rate in weight and height,
      according to type of nursing. The results seem to indicate that infants show a
      delay in growth of weight and height as a result of greater incidence and
      prevalence of diarrhea. It was also shown that human breast milk has a protective
      effect, reducing weight loss from episodes of diarrhea. The study concludes that
      the promotion of breastfeeding, together with the control of diarrheal diseases,
      can provide immediate benefits in improving the nutritional status of the infant
      population.

PMID- 15448817
TI  - [Determinants of malnutrition in a low-income population: hierarchical analytical
      model].
AB  - To investigate the determinants of malnutrition among low-income children, the
      effects of socioeconomic, environmental, reproductive, morbidity, child care,
      birthweight and breastfeeding variables on stunting and wasting were studied. All
      354 children below two years of age living in two urban slum areas of Pelotas,
      southern Brazil, were included. The multivariate analyses took into account the
      hierarchical structure of the risk factors for each type of deficit. Variables
      selected as significant on a given level of the model were considered as risk
      factors, even if their statistical significance was subsequently lost when
      hierarchically inferior variables were included. The final model for stunting
      included the variables education and presence of the father, maternal education
      and employment, birthweight and age. For wasting, the variables selected were the
      number of household appliances, birth interval, housing conditions, borough,
      birthweight, age, gender and previous hospitalizations.

PMID- 15448818
TI  - [Nutritional status of children and occupational categories of the family in a
      rural community of Parana, Brazil].
AB  - The relationship between the occupational category of the family and the
      nutritional status of children was studied. Participants were 340 children up to
      11 years of age, living in a small town of a rural area in Parana, Brazil. The
      nutritional status of the children, as measured in 1983, was related to the
      principal occupational categories of the family in the period 1972- 1983.
      Occupation of the family was categorized as: migrant farmworkers (boias-frias)
      throughout the entire period; renters or sharecroppers that were converted to
      migrant farmworkers; those who never worked as migrant farmworkers; and salaried
      urban workers that were converted to migrant farmworkers. Other variables
      included age and sex of the children, condition of birth (home or hospital),
      number of children up to 11 years of age in the family, birthweight and school
      enrollment of the children 5 years old or over. The prevalence of wasting was
      greatest among children belonging to salaried urban workers that were converted
      to migrant farmworkers. In contrast, this category showed the lowest prevalence
      of stunting. Compared with migrant farmworkers during the entire period, the odds
      ratio of wasting in this category was 2.7 with a 95% confidence interval of 1.3
      5.7. Wasting and stunting were also independently associated with the number of
      children (p<0.05). The larger the family, the lower the risk of wasting, whereas
      for stunting, the larger the family, the higher the risk. These findings suggest
      an important role for the occupational category in the determination of the
      nutritional status in children and indicate that wasting and stunting may have
      differential risk factors.

PMID- 15448819
TI  - [Nutritional surveillance and morbidity of children under 5 years of age seen in
      a primary health care unit: historical series 1987-91].
AB  - This paper presents preliminary analysis of the nutritional status assessment
      (NS) and morbidity of low-income children under 5 years of age seen by the Food
      and Nutritional Surveillance System of a primary health care unit in Rio de
      Janeiro between 1987 and 1991. The distribution of lengh/stature for age (LSA)
      was skewed to the left as early as the first semester of life. Approximately 20%
      of the children had values of body mass for age (BMA) below the 10th percentile
      of the reference growth curve (NCHS). The prevalence of stunting (Z LSA < - 2)
      decreased yearly during the period. The eight most frequent causes of visit to
      the unit were the same but the frequencies varied from year to year. In the last
      three years upper respiratory (URD) and digestive diseases (DD) and
      undernutrition prevailed. NS did not correlate with UPD but the prevalence of DD
      was inversely associated with BMA percentile. These data indicate relevant growth
      deficits in the children which justifies the implementation of nutritional
      surveillance in health units. It is also clear that morbidity and NS must be
      correlated in future studies, so that, the role of nutritional surveillance is
      enhanced in the Health Sector.

PMID- 15448820
TI  - [Physical growth and nutritional status of Brazilian indian populations].
AB  - This paper reviews the literature on the physical growth of native populations
      from Brazil. Studies aiming at relating the physical growth patterns of these
      populations to their nutritional status are relatively recent and still do not
      provide a comprehensive picture of the situation. Compared to non-indigenous
      Brazilian children and international reference populations (NCHS), indigenous
      children are short and light for their age, although they maintain their body
      proportionality, as evaluated by weight for height. These findings could be
      interpreted as an indication of high rates of chronic protein-energy
      undernutrition. At least for some groups, data derived from health surveys
      provide further indication of the existence of marginal nutrition. It is pointed
      out, however, that international reference curves may not be appropriate for
      evaluating the physical growth of specific populations, which may be the case of
      Brazilian indigenous children. It is also pointed out that changes in subsistence
      practices and in health profiles due to the acculturation process may contribute
      to the deterioration of nutritional status of indigenous peoples.

PMID- 15448821
TI  - [Growth and motor performance of schoolchildren from the city of Londrina,
      Parana, Brazil].
AB  - The purpose of this study was to develop an analysis concerning the behavior of
      variables aimed at characterizing growth and motor performance in relation to
      chronological age and gender, attempting to establish the level of importance of
      morphological aspects in modification of functional-motor activity in
      schoolchildren from the city of Londrina, Parana, Brazil. The sample was composed
      of 1,180 randomly-selected subjects, from 7 to 17 years of age. Growth
      characteristics were determined by height and body weight. As for motor
      performance, tests for handgrip strength, sit-and-reach, sit-up, standing long
      jump, and 50- and 1000-meter races were applied. Analysis of results indicated
      that growth variables only begin to present important gender-based differences
      after 15 years of age, while for motor performance differences were found
      favoring boys in almost all motor tests from seven years on, with an increasing
      sexual dimorphism index as the children and adolescents grew. The low (albeit
      statistically significant) correlation between height/body weight and results of
      motor tests indicated that high growth patterns do not necessarily ensure a
      satisfactory motor performance index.

PMID- 15448822
TI  - [Physical maturation: a review with special reference to Brazilian children].
AB  - This article presents an overview of the maturation process in children and
      discusses data from some Brazilian samples. Data related to secondary sexual
      characteristics in both sexes are compared to other populations. The national
      median menarcheal age in Brazilian girls obtained by INAN (1990) was 13.2 years.
      The menarcheal age of Brazilian athletes is higher than the non-athletic
      population. The developmental age of breast, genitals, and pubic hair in
      Brazilian children differ little in relation to European or other Latin American
      populations. Several studies developed in Brazil show that menarche is a landmark
      for the process of fat accumulation in females. However, in boys during the
      sexual maturation process, significant changes in the skinfold thickness amount
      and distribution are not observed. It is evident that there is a lack of studies
      focusing on growth, development, and maturation of adolescents in several regions
      of Brazil, particularly male adolescents.

PMID- 15448823
TI  - [ENDEF and PNSN: trends in physical growth of Brazilian children].
AB  - This paper compares the results of two nationally representative nutritional
      surveys carried out in Brazil: the "Estudo Nacional de Despesa Familiar (ENDEF)"
      (National Survey on Household Expenses), conducted in 1974-77, and the "Pesquisa
      Nacional de Saude e Nutricao (PNSN)" (National Survey on Health and Nutrition),
      conducted in 1989. The findings point to a reduction of more than 60% in the
      prevalence of undernutrition, as evaluated by anthropometric parameters. The
      results from regional surveys and the trends in infant mortality throughout the
      1970s and 1980s are consistent with the improvements in nutritional status. Less
      striking reductions in undernutrition rates were observed in certain regions of
      the country (e.g., the North and Northeast), where prevalences were higher in the
      1970s, resulting in a widening of regional differences. The improvements in child
      nutrition are attributed to moderate increases in family income, particularly in
      the 1970s, and to the expansion of sanitation, public health, and educational
      services, as well as food supplementation programs, which were also favored by a
      fall in fertility levels. The authors call attention to the fact that the lack of
      clear-cut indications of economic recovery in Brazil recently, coupled wih cuts
      in government budgets for social services and the persistence of inequality in
      income distribution, among other factors, make it unlikely that improvements in
      nutritional status, as observed in the 1970, will take place in the upcoming
      years.

PMID- 15448824
TI  - [Variations in tooth formation in individuals from a prehistorical group in
      Santana do Riacho, Lagoa Santa, Minas Gerais, Brazil].
AB  - This article discusses variations in dentogenesis and their consequences when
      estimating age in archaeological samples. One example described here, taken from
      a sample of a Lagoa Santa primeval population found in the Santana do Riacho rock
      shelter in the state of Minas Gerais, Brazil, suggests a need for more research
      concerning patterns of dental growth and maturation in South American indigenous
      populations.

PMID- 15448825
TI  - [Food and nutritional surveillance in Brazil: background, objectives and
      approaches].
AB  - The authors describe the concepts, objectives, components and strategic actions
      that are most frequently recommended for the development of systems of food and
      nutritional surveillance. The study outlines the importance of a continuous
      process of data collection, processing and analysis for the follow-up of food and
      nutritional trends. The System for Food and Nutritional Surveillance could be a
      valuable instrument for the planning, implementation and analysis of programs and
      policies of many international agencies of health and nutrition for the year 2000
      (UNICEF/FAO/WHO). The study analyzes the evolution and current situation of the
      food and nutritional surveillance systems in Brazil, and a relationship is drawn
      between its main problems (coverage, indicators, usage and analytical capacity)
      for the consolidation of the process.

PMID- 15448826
TI  - [On the plan to combat hunger and misery].
AB  - This paper discusses the "Plan Against Hunger and Misery" as it relates to the
      Ministry of Health. The Plan centers around the program "Milk is Health",
      subsidized by the Brazilian Nutritional Surveillance System and aimed at
      undernourished children, his/her close relatives and pregnant women under
      nutritional risks identified in the public health sector. The authors raise
      questions regarding the role(s) to be played by the health system and by the
      Nutritional Surveillance System in the implementation of the Plan, the guidelines
      for food distribution, the indicators for selecting target groups and the
      parameters for evaluating the program "Milk is Health" itself. It is also argued
      that the Plan should value structural modifications, without which it will not be
      possible to ameliorate misery and hunger in Brazil.

PMID- 15448831
TI  - Reports in public health.

PMID- 15448832
TI  - [Effects of occupational exposure to mercury in workers at a light bulb factory
      in Santo Amaro, Sao Paulo, Brazil].
AB  - The aim of this research was to study metallic mercury poisoning in workers at a
      light bulb factory in Santo Amaro, Sao Paulo (Brazil). Visits were made to the
      factory to check both the work environment and the working conditions. Meetings
      with the workers took place in order to better understand the production process
      and how working conditions affect their health. Of the 91 workers investigated,
      77 (84.62%) were chronically poisoned. Among chronically poisoned workers, 76
      (98.70%) displayed neuropsychological alterations, 69 (75.82%) suffered from
      neurological impairments, 62 (68.13%) showed pathological findings under clinical
      examination, and 59 (63.96%) displayed psychiatric disorders.

PMID- 15448833
TI  - [Nutritional deficiencies: specific control measures by the health sector].
AB  - The authors describe and analyze the health sector's role in relation to ways of
      controlling major endemic nutritional deficiencies by reviewing the theoretical
      groundwork and establishing possible regression estimates for the various
      nutritional problems under study. The article is a contribution to the analysis
      of sectorial alternatives elaborated according to United Nations goals (UNICEF -
      WHO - FAO) for the year 2000. Among these goals, we stress reduction of the
      proportion of low birth weight (less than 2500 grams) to less than 10%; reduction
      of anemia cases to one-third of present cases; a reduction of 50% in prevalence
      of moderate and severe cases of malnutrition and the virtual control of vitamin A
      and iodine deficiencies.

PMID- 15448834
TI  - [Action-oriented information systems: subsidies for activities by workers' health
      programs at the local level].
AB  - Over the course of recent decades, Brazil has become an industrialized society.
      From an epidemiological perspective and considering changes that have been
      occurring in the Brazilian population, particularly concerning demographic and
      epidemiological transitions, this paper discusses the need to adapt the
      epidemiological surveillance system in order to incorporate the surveillance of
      non-transmissible diseases. The authors analyze the information system for work
      related accidents in the Workers' Health Program, under SUDS (the Unified
      Decentralized Health System) for the Mandaqui Region (in the Northern part of the
      city of Sao Paulo), based on data from a local metalworking industry identified
      by the information system as a high-risk site for work-related accidents. The
      article also focuses on the importance of organized workers participating in
      actions to control work-related accidents. Although such participation is not
      always possible, the health sector must incorporate the workers' own concrete
      experience in order to develop more effective actions to prevent accidents at the
      workplace.

PMID- 15448835
TI  - [Measuring the impact of promoting breastfeeding in primary health care services
      in Pelotas, Rio Grande do Sul, Brazil].
AB  - All mothers with children enrolled in the Program for Child Growth and
      Development at primary care units belonging to the Federal University of Pelotas
      (UFPel) in the state of Rio Grande do Sul, Brazil, were interviewed with a
      standardized questionnaire. This research aimed to assess the impact of the
      "Groups of Expecting Mothers" in the promotion of breastfeeding. The family
      income of almost half of the 347 children studied was two times the minimum wage.
      About 1/4 of the children's mothers had spent less than four years in school, and
      these were the mothers who attended the Groups most frequently. Most of the
      mothers received prenatal care and nearly half of then participated in the
      Groups. In contrast, 1/3 of the children were weaned at the age of three months
      and almost 80% received tea in the early months of life. The results show that
      the Groups of Expecting Mothers suffer serious limitations in promoting
      breastfeeding and in postponing the introduction of foods other than breast milk
      in the children's diet. Data obtained in this study are intended to help
      strengthen action under current programs and to show that with minimum resources
      and a rather simple methodology it is possible to assess the quality of health
      services available to the population.

PMID- 15448836
TI  - [Exposure to organic mercury in riparian populations on the Upper Madeira river,
      Rondonia, Brazil, 1991: preliminary results].
AB  - This study analyzes mercury concentration in hair samples obtained from the
      population living in the Upper Madeira River basin, Rondonia. Out of 311 hair
      samples analyzed, 51% (n=158) had a mercury concentration of over 10 ppm. The
      wide variability of mercury concentration is well-illustrated by a family in
      which there were 5 cases with the highest mercury concentrations (90.6 to 303.1
      ppm), while in another 5 household members, the concentration ranged from 7.0 to
      13.3 ppm. Special attention must be paid to women in the childbearing age, since
      the fetus is more vulnerable to lower mercury concentrations. 53% (n=37) females
      in the reproductive age bracket (age group 4) displayed a mercury concentration
      above 10 ppm.

PMID- 15448837
TI  - [A critical appraisal of an institutional journal: Memorias do Instituto Oswaldo
      Cruz].
AB  - The journal Memorias do Instituto Oswaldo Cruz, founded and maintained over the
      course of many years for the exclusive publication of research results from one
      single institution, has undergone changes over the last decade which have
      resulted in an open journal. Conditions leading to the journal's founding and the
      excellent role it has played in the dissemination of knowledge produced by the
      Instituto Oswaldo Cruz are examined. The fact that it has differed from journals
      published by scientific societies does not diminish its importance. The present
      option to give this journal an international slant, with possibilities for
      competing on the foreign market, and which would be facilitated by the preference
      given to papers written in English, raises some questions about the role of
      Brazilian specialized journals within the framework of our scientific
      development.

PMID- 15448838
TI  - Long-term controlled field experiment on the competition between two species of
      Biomphalaria (Mollusca, Basommatophora), the snail vectors of Schistosoma mansoni
      in Northeastern Brazil.
AB  - A long-term controlled field experiment on the interactions of the populations of
      Biomphalaria glabrata (target population) and B. straminea (competitor) was
      carried out in the county of Alhandra, state of Paraiba, Brazil, during the
      period 1980 through 1989. Results obtained in the current paper show that the
      snail B. straminea has strong competitive advantages over B. glabrata. In six out
      of nine streams the native population of B. glabrata were totally excluded and
      replaced by B. straminea. There is evidence showing that seasonal dryness has
      marked influence on the phenomenon studied in this paper. In all the streams were
      B. straminea already predominated, return of B. glabrata was never observed.

PMID- 15448839
TI  - [Public health, local health units, and the Brazilian health system].
AB  - This article focuses on the development of public health in Brazil, with the aim
      of analyzing the present process of decentralization of health care. The authors
      argue that the neoliberal or conservative position is unable to offer a
      reasonable solution to problems in the health care system. On the other hand, the
      reformist position concentrates its attention on the health system and its
      administration, taking as its model a positivistic approach to natural and
      administrative sciences. The authors further argue that only a radical change in
      the prevailing medical paradigm and a predominance of social over biological
      aspects would meet the health needs of the population.

PMID- 15448840
TI  - [Smoking prevalence among students from a metropolitan area in the southern
      region of Brazil, 1991].
AB  - A prevalence study on smoking habits was carried out in 1991, among 864 school
      children from eight municipal schools in Sapiranga, in the State of Rio Grande do
      Sul, Brazil, from the 6th through 8th grade of primary school. Data was collected
      in class, using a questionnaire applied by trained teachers. Among students, 3.2%
      were smokers, although 20.3% had been exposed to tobacco. Males had begun the
      smoking habit at a mean age of 14.7 years and females at about 15 years old. The
      prevalence showed an increasing trend by age and individual school grade. As for
      gender, male smokers outnumbered females (p < 0,05). Smoking by older brothers
      and fathers seems to be positively associated with acquisition of the habit by
      school children.

PMID- 15448841
TI  - [Health surveys from a planning perspective].
AB  - This study examines the importance of household surveys for evaluating the
      implementation of district-based health systems for the delivery of health
      services. The concepts underlying health surveys and the literature on health
      surveys in the Third World are reviewed, and significant methodological problems
      are also discussed. Although many authors dealing with this issue consider
      household health surveys of capital importance for the planning of health
      services, that was not the situation encountered by the author, who rarely found
      examples of the applicability of such studies. The potential use of less complex
      and quicker studies was a solution proposed by some authors to increase the
      presence of surveys in health planning. Finally, national health surveys are also
      analyzed.

PMID- 15448842
TI  - [Chagas' disease and its control in Latin America: an analysis of possibilities].
AB  - Chagas' disease is still a major public health problem in Latin America,
      affecting about 15 million individuals and leaving tens of millions of others at
      risk, most of whom are from rural areas and are socially marginalized. The main
      strategies and tools for the control of the disease are related to the vectorial
      and transfusional transmission of the parasite. Regular programs have proven
      effective, as in Brazil, and they depend basically on political will and basic
      technical and financial conditions. Epidemiologic and operational aspects of
      Chagas' disease control are discussed in this study, involving the reformulation
      and improvement of the health systems in affected countries. The fact that
      control can be attained is emphasized as a challenge to Latin American
      governments and public health officials. Control of Chagas' disease may be an
      additional part of the dream of Latin American unity.

PMID- 15448849
TI  - Cadernos de Saude Publica.

PMID- 15448843
TI  - [The reorganization of health services: reflections on the relationship between
      decentralization, local autonomy and citizens' participation].
AB  - This paper discusses certain historical and theoretical aspects pertaining to the
      concepts of decentralization, local autonomy, and citizens' participation in
      studies on the reorganization of health services. Further studies should be
      undertaken to identify determinants of and limits to the reorganization of health
      services, greater local autonomy and citizens' participation. Various hypotheses
      and future courses of study are proposed.

PMID- 15448850
TI  - [Neocorporatist arrangements and defense of physicians' interests].
AB  - In Brazil, the trade union structure created by authoritarian corporatism in the
      1930's began to change when the cycle of the military regime installed in 1964
      came to an end. With redemocratization, the trade union movement began to coexist
      with the organization of pluralistic interests, a process which has influenced
      the physicians' movement since 1977. The new National Constitution adopted in
      1988 provided for multipartite control over health policy. We present a
      conceptual discussion of neocorporatist arrangements (which are common in
      European social experience) and their significance for an understanding of health
      policy in the context of the so called Health Reform process in Brazil.

PMID- 15448851
TI  - [Who cares how doctors and patients relate?].
AB  - The relationship between doctors and their patients is part of everyday life for
      thousands of professionals. In order to avoid an idealistic or merely emotional
      approach to this question, it is necessary to investigate how it is related to
      medical science and to the overall relationship between medicine and society.
      Indeed, far from being aleatory, the doctor-patient relationship as it has been
      practiced can be understood as a tool for maintaining the power of both the
      medical establishment and the state over society. To change this practice, the
      author proposes two different approaches to specific fields of medical practice:
      the hospital and non-hospital fields. In the field outside hospitals, the
      humanization of medical practice depends basically on broadened training for
      professionals in order to prepare them to deal with this work's inherent demands,
      where a physiopathological approach is often insufficient. Inside hospitals, a
      more humanistic relationship depends more directly on the action of a
      multiprofessional health team.

PMID- 15448852
TI  - [The development of epidemiological surveillance systems for smallpox and
      poliomyelitis: changing concepts in operational categories].
AB  - This article describes the process by which some concepts of epidemiological
      surveillance are elaborated and turned into operational categories to comprise
      the so-called epidemiological surveillance system for two specific diseases. The
      authors describe some epidemiological concepts and categories which were
      elaborated over the course of the smallpox eradication program and more recently
      in the poliomyelitis eradication program. Such concepts and categories as
      outbreak containment, cross-notification, and case definitions are described as
      they fit into a series of actions which make up the epidemiological surveillance
      system. Finally, it is worth noting that the description developed in this
      article is based on personal observations, since the authors participated in the
      smallpox eradication program in Bangladesh and Somalia as well as in the regional
      poliomyelitis eradication program in the Americas.

PMID- 15448853
TI  - [Discovering pathways for health research in dealing with the social movement].
AB  - This article is about methodology for scientific research in health, where the
      researcher is an important part of the object of investigation. The
      implementation of a broad-based Health Reform in Brazil depends on the
      involvement of users. It is important to guarantee these social rights. Many
      experiences sharing this concern are going on in this country. Still, research on
      the relationship between institutional work in health and the Social Movement
      lacks a predefined methodology. Therefore, the main objectives of this study are
      the following: to contribute to the discussion of possible ways of approaching
      the mechanisms of relationships between health and users of health services, and
      to collaborate with the development of the citizenship process. This work was
      done through theoretical research on participatory methodology and "action-based
      research". The following aspects are particularly important: definition of the
      object of study, self-positioning by the researcher, subjective explanations,
      documentary surveys and interviews for case studies, and feedback to theory.
      Finally, the author concludes that this methodology allows for an understanding
      of some mechanisms that explain the relationship between macro- and micro
      structural analyses. In addition, one also observes a maturation process in the
      research protagonists.

PMID- 15448854
TI  - [Concealed and revealed violence: an epidemiological study of mortality from
      external causes in Duque de Caxias, Rio de Janeiro].
AB  - This paper is part of an interdisciplinary study dealing with violence and the
      health process in the city of Duque de Caxias, State of Rio de Janeiro. This
      process expresses structural violence in addition to that related to resistance
      and deliquency, the outcomes of which are present in the area's overall
      mortality. This is an analysis of recorded data on mortality form external causes
      in the period 1979-1987, as well as a critical analysis of information gathered
      from death certificates for the year 1987. Mortality from external causes in the
      area studied is shown according to its magnitude and importance in relation to
      the major causes of death in the city, using absolute numbers, ratios, crude and
      standardized coefficients, rates, and years of life potentially lost, which are
      classified by groups of specific external causes, sex, and age. The analysis
      gives a socio-economic and demographic profile of the victims. The findings are
      discussed in the light of the sociological and historical knowledge on the social
      dynamics of Duque de Caxias. As a conclusion, this paper suggests a few actions
      that are badly needed for providing support to the victims of violence.

PMID- 15448855
TI  - [Violence for all].
AB  - This paper investigates the problem of social violence based on the situation for
      mortality from external causes in Brazil, particularly in the city of Rio de
      Janeiro. Mortality data from the Brazilian Ministry of Health (consolidated by
      the Department of Epidemiology of the National School of Public Health in the
      period 1980-1988) are used in this study. Proportional mortality and mortality
      rates from external causes are given according to sex, age, specific groups of
      external causes, types of homicides, and traffic accidents. Despite being
      basically a descriptive study, this paper also studies homicides as the most
      significant cause of death in the configuration of violence in Brazil today.

PMID- 15448856
TI  - [The political and administrative context of the implementation of Health
      Districts in the State of Bahia, Brazil].
AB  - This investigation was conducted in order to determine the political and
      administrative context prevailing during the implementation of health districts
      in the state of Bahia, Brazil. The documentary review includes laws, agreements,
      and contracts at the State and Federal levels from 1987 to 1989. This period
      corresponded to the first phase of the State government after the 1986 elections.
      Information was also obtained from key informants and former directors of the
      State Secretariat of Health at the central level. We describe how the policy for
      regionalization by territory and population was formulated, and we review both
      State and national planning procedures, identifying the events leading to the
      decision to create health districts. We list the political instruments related to
      this decision and analyze the positions of the various actors in the Brazilian
      Health System in relation to this strategic choice. Brief comments are given
      about the difficulties faced by this proposal during the period studied.

PMID- 15448857
TI  - [An alternative model for schistosomiasis control: the present status of the
      project in the State of Espirito Santo, Brazil].
AB  - An intervention study for schistosomiasis control is being carried out in the
      county of Afonso Claudio, state of Espirito Santo, Brazil, having begun in
      February 1992. This study is an alternative response to classical control
      methods. The project is being developed using an interdisciplinary approach and
      involves both research and service institutions. The organization of health
      services at the primary care level is part of the project. Participant
      observation is seen as the methodological point of departure for guiding data
      collection and analysis and the intervention process in local reality. Control
      methods are restricted to the medical treatment given to all infected individuals
      and to improvements in the sanitation facilities available in the area. These
      methods are obviously integrated with the above-mentioned social actions.
      Consisting of three phases - pre-control, control (intervention), and final
      evaluation - the project is now in its intervention phase, lasting approximately
      three years.

PMID- 15448859
TI  - [Not Available].

PMID- 15448858
TI  - [The hidden face of AIDS in Brazil].
AB  - The authors report on the evolution of the AIDS epidemic in Brazil from the point
      of view of the construction of social representations about "risk groups"
      involved in the spread of the disease. They emphasize the need to demystify the
      immediate correlation between AIDS and homosexual transmission. They highlight
      the role of intravenous drug users and of heterosexual transmission in new AIDS
      cases in Brazil - groups and behaviours that are not included in the priorities
      of local health authorities.

PMID- 15448863
TI  - A strategy for obtaining social benefits from the gene revolution.
AB  - The strategy described in the present paper offers details about the possibility
      for Brazil to play a more substantial role in the gene revolution. If
      successfully applied, the powerful science-based technology currently available
      in Brazil can contribute to extend the benefits of the gene revolution to the
      poorest countries, very much like the Green Revolution did in the past, thereby
      reducing the hunger syndrome which claimed the lives of millions of people in
      some Asian countries, particularly Pakistan and India, decades ago. In his visit
      to Brazil in February 2004, Norman Borlaug had the opportunity to witness the
      success of Brazilian agriculture. At a Conference held at ESALQ - Superior School
      of Agriculture Luiz de Queiroz in Piracicaba, SP, Brazil, he stated that the 21st
      century revolution will come from Brazil in the area of agriculture. He also said
      that reducing hunger is essential for the world to achieve socioeconomic
      stability. A central question remains unanswered: who will fund this revolution?
      The FAO 2003-2004 Annual Report listed the barriers preventing the gene
      revolution from reaching the poorest countries: inadequate regulatory procedures
      Intellectual Property Rights and Biosafety, poorly functioning seed delivering
      systems and weak domestic plant breeding capacity; all are discussed in this
      paper.

PMID- 15448864
TI  - Control of the rat angiotensin I converting enzyme gene by CRE-like sequences.
AB  - We characterized the role of potential cAMP-responsive elements (CRE) in basal
      and in induced angiotensin converting enzyme (ACE) gene promoter activity in
      order to shed light on the regulation of somatic ACE expression. We identified
      stimulators and repressors of basal expression between 122 and 288 bp and between
      415 and 1303 bp upstream from the transcription start site, respectively, using a
      rabbit endothelial cell (REC) line. These regions also contained elements
      associated with the response to 8BrcAMP. When screening for CRE motifs we found
      pCRE, a proximal sequence between 209 and 222 bp. dCRE, a distal tandem of two
      CRE-like sequences conserved between rats, mice and humans, was detected between
      834 and 846 bp. Gel retardation analysis of nuclear extracts of REC indicated
      that pCRE and dCRE bind to the same protein complexes as bound by a canonical
      CRE. Mutation of pCRE and dCRE in REC established the former as a positive
      element and the latter as a negative element. In 293 cells, a renal cell line,
      pCRE and dCRE are negative regulators. Co-transfection of ATF-2 or ATF-2 plus c
      Jun repressed ACE promoter activity, suggesting that the ACE gene is controlled
      by cellular stress. Although mapping of cAMP responsiveness was consistent with
      roles for pCRE and dCRE, mutation analysis indicated that they were not required
      for cAMP responsiveness. We conclude that the basal activity of the somatic ACE
      promoter is controlled by proximal and distal CREs that can act as enhancers or
      repressors depending on the cell context.

PMID- 15448865
TI  - Respiration, oxidative phosphorylation, and uncoupling protein in Candida
      albicans.
AB  - The respiration, membrane potential (Deltapsi), and oxidative phosphorylation of
      mitochondria in situ were determined in spheroplasts obtained from Candida
      albicans control strain ATCC 90028 by lyticase treatment. Mitochondria in situ
      were able to phosphorylate externally added ADP (200 microM) in the presence of
      0.05% BSA. Mitochondria in situ generated and sustained stable mitochondrial
      Deltapsi respiring on 5 mM NAD-linked substrates, 5 mM succinate, or 100 microM
      N,N,N',N'-tetramethyl-p-phenylenediamine dihydrochloride plus 1 mM ascorbate.
      Rotenone (4 microM) inhibited respiration by 30% and 2 micro M antimycin A or
      myxothiazole and 1 mM cyanide inhibited it by 85%. Cyanide-insensitive
      respiration was partially blocked by 2 mM benzohydroxamic acid, suggesting the
      presence of an alternative oxidase. Candida albicans mitochondria in situ
      presented a carboxyatractyloside-insensitive increase of Deltapsi induced by 5 mM
      ATP and 0.5% BSA, and Deltapsi decrease induced by 10 microM linoleic acid, both
      suggesting the existence of an uncoupling protein. The presence of this protein
      was subsequently confirmed by immunodetection and respiration experiments with
      isolated mitochondria. In conclusion, Candida albicans ATCC 90028 possesses an
      alternative electron transfer chain and alternative oxidase, both absent in
      animal cells. These pathways can be exceptional targets for the design of new
      chemotherapeutic agents. Blockage of these respiratory pathways together with
      inhibition of the uncoupling protein (another potential target for drug design)
      could lead to increased production of reactive oxygen species, dysfunction of
      Candida mitochondria, and possibly to oxidative cell death.

PMID- 15448866
TI  - Low variation in ribosomal DNA and internal transcribed spacers of the symbiotic
      fungi of leaf-cutting ants (Attini: Formicidae).
AB  - Leaf-cutting ants of the genera Atta and Acromyrmex (tribe Attini) are symbiotic
      with basidiomycete fungi of the genus Leucoagaricus (tribe Leucocoprineae), which
      they cultivate on vegetable matter inside their nests. We determined the
      variation of the 28S, 18S, and 5.8S ribosomal DNA (rDNA) gene loci and the
      rapidly evolving internal transcribed spacers 1 and 2 (ITS1 and ITS2) of 15
      sympatric and allopatric fungi associated with colonies of 11 species of
      leafcutter ants living up to 2,600 km apart in Brazil. We found that the fungal
      rDNA and ITS sequences from different species of ants were identical (or nearly
      identical) to each other, whereas 10 GenBank Leucoagaricus species showed higher
      ITS variation. Our findings suggest that Atta and Acromyrmex leafcutters living
      in geographic sites that are very distant from each other cultivate a single
      fungal species made up of closely related lineages of Leucoagaricus
      gongylophorus. We discuss the strikingly high similarity in the ITS1 and ITS2
      regions of the Atta and Acromyrmex symbiotic L. gongylophorus studied by us, in
      contrast to the lower similarity displayed by their non-symbiotic counterparts.
      We suggest that the similarity of our L. gongylophorus isolates is an indication
      of the recent association of the fungus with these ants, and propose that both
      the intense lateral transmission of fungal material within leafcutter nests and
      the selection of more adapted fungal strains are involved in the homogenization
      of the symbiotic fungal stock.

PMID- 15448867
TI  - Effect of one stretch a week applied to the immobilized soleus muscle on rat
      muscle fiber morphology.
AB  - We determined the effect of stretching applied once a week to the soleus muscle
      immobilized in the shortened position on muscle fiber morphology. Twenty-six male
      Wistar rats weighing 269 +/- 26 g were divided into three groups. Group I, the
      left soleus was immobilized in the shortened position for 3 weeks; group II, the
      soleus was immobilized in the shortened position and stretched once a week for 3
      weeks; group III, the soleus was submitted only to stretching once a week for 3
      weeks. The medial part of the soleus muscle was frozen for histology and muscle
      fiber area evaluation and the lateral part was used for the determination of
      number and length of serial sarcomeres. Soleus muscle submitted only to
      immobilization showed a reduction in weight (44 +/- 6%, P = 0.002), in serial
      sarcomere number (23 +/- 15%) and in cross-sectional area of the fibers (37 +/-
      31%, P < 0.001) compared to the contralateral muscles. The muscle that was
      immobilized and stretched showed less muscle fiber atrophy than the muscles only
      immobilized (P < 0.05). Surprisingly, in the muscles submitted only to
      stretching, fiber area was decreased compared to the contralateral muscle (2548
      +/- 659 vs 2961 +/- 806 microm(2), respectively, P < 0.05). In conclusion,
      stretching applied once a week for 40 min to the soleus muscle immobilized in the
      shortened position was not sufficient to prevent the reduction of muscle weight
      and of serial sarcomere number, but provided significant protection against
      muscle fiber atrophy. In contrast, stretching normal muscles once a week caused a
      reduction in muscle fiber area.

PMID- 15448868
TI  - Effect of chronic fish oil supplementation on renal function of normal and
      cachectic rats.
AB  - In the present study we determined the effect of chronic diet supplementation
      with n-3 PUFA on renal function of healthy and cachectic subjects by providing
      fish oil (1 g/kg body weight) to female rats throughout pregnancy and lactation
      and then to their offspring post-weaning and examined its effect on renal
      function parameters during their adulthood. The animals were divided into four
      groups of 5-10 rats in each group: control, control supplemented with fish oil
      (P), cachectic Walker 256 tumor-bearing (W), and W supplemented with fish oil
      (WP). Food intake was significantly lower in the W group compared to control
      (12.66 +/- 4.24 vs 25.30 +/- 1.07 g/day). Treatment with fish oil significantly
      reversed this reduction (22.70 +/- 2.94 g/day). Tumor growth rate was markedly
      reduced in the P group (16.41 +/- 2.09 for WP vs 24.06 +/- 2.64 g for W). WP
      group showed a significant increase in mean glomerular filtration rate compared
      to P and control (1.520 +/- 0.214 ml min-1 kg body weight-1; P < 0.05). Tumor
      bearing groups had low urine osmolality compared to control rats. The fractional
      sodium excretion decreased in the W group compared to control (0.43 +/- 0.16 vs
      2.99 +/- 0.87%; P < 0.05), and partially recovered in the WP group (0.90 +/-
      0.20%). In summary, the chronic supplementation with fish oil used in this study
      increased the amount of fat in the diet by only 0.1%, but caused remarkable
      changes in tumor growth rate and cachexia, also showing a renoprotective
      function.

PMID- 15448869
TI  - Effect of bullfrog (Rana catesbeiana) oil administered by gavage on the fatty
      acid composition and oxidative stress of mouse liver.
AB  - The aim of the present study was to investigate the effects of daily intragastric
      administration of bullfrog oil (oleic, linoleic and palmitoleic acid-rich oil),
      corresponding to 0.4% of body weight for four weeks, on fatty acid composition
      and oxidative stress (lipid peroxidation and catalase activity) in mouse liver.
      The activities of aspartate aminotransferase (AST), alkaline phosphatase (ALP),
      alanine aminotransferase (ALT), and gamma-glutamyltransferase (GGT), biomarkers
      of tissue injury, were determined in liver homogenates and serum. The proportions
      of 18:2n-6, 20:4n-6, 20:5n-3, and 22:6n-3 (polyunsaturated fatty acids, from 37
      to 60%) in the total fatty acid content were increased in the liver of the
      bullfrog oil-treated group (P < 0.05) compared to control. At the same time, a
      significant decrease in the relative abundance of 14:0, 16:0, and 18:0 (saturated
      fatty acids, from 49 to 25%) was observed. The hepatic content of thiobarbituric
      acid reactive substances (TBARS) was increased from 2.3 +/- 0.2 to 12.3 +/- 0.3
      nmol TBA-MDA/mg protein and catalase activity was increased from 840 +/- 32 to
      1110 +/- 45 micromol reduced H2O2 min-1 mg protein-1 in the treated group.
      Bullfrog oil administration increased AST and ALP activities in the liver (from
      234.10 +/- 0.12 to 342.84 +/- 0.13 and 9.38 +/- 0.60 to 20.06 +/- 0.27 U/g,
      respectively) and in serum (from 95.41 +/- 6.13 to 120.32 +/- 3.15 and 234.75 +/-
      11.5 to 254.41 +/- 2.73 U/l, respectively), suggesting that this treatment
      induced tissue damage. ALT activity was increased from 287.28 +/- 0.29 to 315.98
      +/- 0.34 U/g in the liver but remained unchanged in serum, whereas the GGT
      activity was not affected by bullfrog oil treatment. Therefore, despite the
      interesting modulation of fatty acids by bullfrog oil, a possible therapeutic use
      requires care since some adverse effects were observed in liver.

PMID- 15448870
TI  - Immunoglobulin E and systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by
      intense polyclonal production of autoantibodies and circulating immune complexes.
      Some reports have associated SLE with a Th2 immune response and allergy. In the
      present study 21 female patients with SLE were investigated for total IgE and IgE
      antibodies to dust house aeroallergens by an automated enzyme-linked fluorescent
      assay, and were also evaluated for antinuclear IgE autoantibodies by a modified
      indirect immunofluorescence test using HEp-2 cells as antigen substrate.
      Additionally, immunocapture ELISA was used to investigate serum anti-IgE IgG
      autoantibodies. Serum IgE above 150 IU/ml, ranging from 152 to 609 IU/ml (median
      = 394 IU IgE/ml), was observed in 7 of 21 SLE patients (33%), 5 of them
      presenting proteinuria, urinary cellular casts and augmented production of anti
      dsDNA antibodies. While only 2 of 21 SLE patients (9.5%) were positive for IgE
      antibodies to aeroallergens, all 10 patients with respiratory allergy (100%) from
      the atopic control group (3 males and 7 females), had these immunoglobulins. SLE
      patients and healthy controls presented similar anti-IgE IgG autoantibody titers
      (X = 0.37 +/- 0.20 and 0.34 +/- 0.18, respectively), differing from atopic
      controls (0.94 +/- 0.26). Antinuclear IgE autoantibodies were detected in 17 of
      21 (81%) sera from SLE patients, predominating the fine speckled pattern of
      fluorescence, that was also observed in IgG-ANA. Concluding, SLE patients can
      present increased IgE levels and antinuclear IgE autoantibodies without specific
      clinical signs of allergy or production of antiallergen IgE antibodies, excluding
      a possible association between SLE and allergy.

PMID- 15448871
TI  - Neonatal administration of citalopram delays somatic maturation in rats.
AB  - We investigated the somatic maturation of neonate rats treated during the
      suckling period with citalopram, a selective serotonin reuptake inhibitor. Groups
      with 6 male neonates were randomly assigned to different treatments 24 h after
      birth. Each litter was suckled by one of the dams until the 21st postnatal day.
      Body weight, head axis and tail length were measured daily from the 1st to the
      21st postnatal day. Time of ear unfolding, auditory conduit opening, incisor
      eruption, and eye opening was determined. Pups received 5 mg (Cit5), 10 mg
      (Cit10) or 20 mg/kg (Cit20) citalopram sc, or saline (0.9% NaCl, w/v, sc).
      Compared to saline, body weight was lower (24.04%, P < 0.01) for Cit10 from the
      10th to the 21st day and for Cit20 from the 6th to the 21st day (38.19%, P <
      0.01). Tail length was reduced in the Cit20 group (15.48%, P < 0.001) from the
      8th to the 21st day. A reduction in mediolateral head axis (10.53%, P < 0.05) was
      observed from the 11th to the 21st day in Cit10 and from the 6th to the 21st day
      in Cit20 (13.16%, P < 0.001). A reduction in anteroposterior head axis was also
      observed in the Cit20 group (5.28%, P < 0.05) from the 13th to the 21st day.
      Conversely, this axis showed accelerated growth from the 12th to the 21st day in
      the Cit5 group (13.05%, P < 0.05). Auditory conduit opening was delayed in the
      Cit5 and Cit20 groups and incisor eruption was delayed in all citalopram groups.
      These findings show that citalopram injected during suckling to rats induces body
      alterations and suggest that the activity of the serotoninergic system
      participates in growth mechanisms.

PMID- 15448872
TI  - Comparison of voluntary ethanol intake by two pairs of rat lines used as genetic
      models of anxiety.
AB  - The relationship between anxiety-related behaviors and voluntary ethanol intake
      was examined in two pairs of rat lines by the oral ethanol self-administration
      procedure. Floripa high (H) and low (L) rats selectively bred for contrasting
      anxiety responses in the open-field test, and two inbred strains, spontaneously
      hypertensive rats (SHR) and Lewis rats which are known to differ significantly
      when submitted to several behavioral tests of anxiety/emotionality, were used (9
      10 animals/line/sex). No differences in the choice of ethanol solutions (2%, days
      1-4, and 4%, days 5-8, respectively) in a 2-bottle paradigm were detected between
      Floripa H and L rats (1.94 +/- 0.37 vs 1.61 +/- 0.37 g/kg for ethanol intake on
      day 8 by the Floripa H and L rat lines, respectively). Contrary to expectations,
      the less anxious SHR rats consumed significantly more ethanol than Lewis rats
      (respective intake of 2.30 +/- 0.45 and 0.72 +/- 0.33 g/kg on day 8) which are
      known to be both addiction-prone and highly anxious. Regardless of strain, female
      rats consumed more ethanol than males (approximately 46%). The results showed no
      relationship between high anxiety and voluntary intake of ethanol for Floripa H
      and L rats. A negative association between these two variables, however, was
      found for SHR and Lewis rat strains. Data from the literature regarding the
      association between anxiety and alcohol intake in animal models are not
      conclusive, but the present results indicate that factors other than increased
      inborn anxiety probably lead to the individual differences in ethanol drinking
      behavior.

PMID- 15448873
TI  - The mental health of graduate students at the Federal University of Sao Paulo: a
      preliminary report.
AB  - We present data regarding the care provided to graduate level health
      professionals at the mental health center of the Federal University of Sao Paulo.
      From September 1996 to September 2003, 146 graduate students (99 in the Master's
      degree program and 47 in the Doctoral program) were attended. This population was
      predominantly female (68.5%), with a mean (+/- SD) age of 28.6 +/- 4.42 years,
      not married (71.9%). Most of the subjects were professionals who had not
      graduated from the Federal University (78.1%). The students who sought help for
      psychological and/or psychiatric problems were classified into two categories:
      situational-adaptive crises and psychopathological crises. The main diagnoses
      were depression and anxiety disorders (44%) causing 4.5% of the subjects to be
      temporarily suspended from their graduate studies; 19.2% reported that they had
      used psychotropic drugs within the previous month, and 47.9% referred to sleep
      disturbances. Suicidal tendencies were mentioned by 18% of those interviewed.
      Students with emotional disturbances and academic dysfunctions should be
      recognized at an early stage, and it is fundamental for them to have access to
      mental health programs that provide formal, structured and confidential care.
      Thus, it is important that professors and advisors in graduate programs build a
      warm and affective learning environment. If we consider the expressive growth in
      Brazilian scientific production resulting from the implementation of an extensive
      national system of graduate education, it is important to focus efforts on
      enhancing and upgrading the mental health care system.

PMID- 15448874
TI  - Thalidomide and pentoxifylline block the renal effects of supernatants of
      macrophages activated with Crotalus durissus cascavella venom.
AB  - Because thalidomide and pentoxifylline inhibit the synthesis and release of tumor
      necrosis factor-alpha (TNF-alpha), we determined the effect of these drugs on the
      renal damage induced by supernatants of macrophages activated with Crotalus
      durissus cascavella venom in order to identify the role of TNF-alpha in the
      process. Rat peritoneal macrophages were collected with RPMI medium and
      stimulated in vitro with C.d. cascavella venom (10 micro g/ml) in the absence and
      presence of thalidomide (15 micro M) or pentoxifylline (500 micro M) for 1 h and
      washed and kept in culture for 2 h. Supernatant (1 ml) was tested on an isolated
      perfused rat kidney (N = 6 for each group). The first 30 min of each experiment
      were used as control. The supernatant was added to the perfusion system. All
      experiments lasted 120 min. The toxic effect of the preparation of venom
      stimulated macrophages on renal parameters was determined. At 120 min,
      thalidomide (Thalid) and pentoxifylline (Ptx) inhibited (P < 0.05) the increase
      in perfusion pressure caused by the venom (control = 114.0 +/- 1.3; venom = 137.1
      +/- 1.5; Thalid = 121.0 +/- 2.5; Ptx = 121.4 +/- 4.0 mmHg), renal vascular
      resistance (control = 4.5 +/- 0.2; venom = 7.3 +/- 0.6; Thalid = 4.5 +/- 0.9; Ptx
      = 4.8 +/- 0.6 mmHg/ml g-1 min-1), urinary flow (control = 0.23 +/- 0.001; venom =
      0.44 +/- 0.01; Thalid = 0.22 +/- 0.007; Ptx = 0.21 +/- 0.009 ml g-1 min-1),
      glomerular filtration rate (control = 0.72 +/- 0.06; venom = 1.91 +/- 0.11;
      Thalid = 0.75 +/- 0.04; Ptx = 0.77 +/- 0.05 ml g-1 min-1) and the decrease in
      percent tubular sodium transport (control = 77.0 +/- 0.9; venom = 73.9 +/- 0.66;
      Thalid = 76.6 +/- 1.1; Ptx = 81.8 +/- 2.0%), percent tubular chloride transport
      (control = 77.1 +/- 1.2; venom = 71.4 +/- 1.1; Thalid = 77.6 +/- 1.7; Ptx = 76.8
      +/- 1.2%), and percent tubular potassium transport (control = 72.7 +/- 1.1; venom
      = 63.0 +/- 1.1; Thalid = 72.6 +/- 1.0; Ptx = 74.8 +/- 1.0%), 30 min before and
      during the stimulation of macrophages with C.d. cascavella venom. These data
      suggest the participation of TNF-alpha in the renal effects induced by
      supernatant of macrophages activated with C.d. cascavella venom.

PMID- 15448875
TI  - Antinociceptive effect of novel pyrazolines in mice.
AB  - The antinociceptive effect of six novel synthetic pyrazolines (3-ethoxymethyl-5
      ethoxycarbonyl-1H-pyrazole (Pz 1) and its corresponding 1-substituted methyl (Pz
      2) and phenyl (Pz 3) analogues, and 3-(1-ethoxyethyl)-5-ethoxycarbonyl-1H
      pyrazole (Pz 4) and its corresponding 1-substituted methyl (Pz 5) and phenyl (Pz
      6) analogues) was evaluated by the tail immersion test in adult male albino mice.
      The animals (N = 11-12 in each group) received vehicle (5% Tween 80, 10 ml/kg,
      sc) or 1.5 mmol/kg of each of the pyrazolines (Pz 1-Pz 6), sc. Fifteen, thirty
      and sixty minutes after drug administration, the mice were subjected to the tail
      immersion test. Thirty minutes after drug administration Pz 2 and Pz 3 increased
      tail withdrawal latency (vehicle = 3.4 +/- 0.2; Pz 2 = 5.2 +/- 0.4; Pz 3 = 5.9 +/
      0.4 s; mean +/- SEM), whereas the other pyrazolines did not present
      antinociceptive activity. Dose-effect curves (0.15 to 1.5 mmol/kg) were
      constructed for the bioactive pyrazolines. Pz 2 (1.5 mmol/kg, sc) impaired motor
      coordination in the rotarod and increased immobility in the open-field test. Pz 3
      did not alter rotarod performance and spontaneous locomotion, but increased
      immobility in the open field at the dose of 1.5 mmol/kg. The involvement of
      opioid mechanisms in the pyrazoline-induced antinociception was investigated by
      pretreating the animals with naloxone (2.75 micro mol/kg, sc). Naloxone prevented
      Pz 3- but not Pz 2-induced antinociception. Moreover, naloxone pretreatment did
      not alter Pz 3-induced immobility. We conclude that Pz 3-induced antinociception
      involves opioid mechanisms but this is not the case for Pz 2.

PMID- 15448876
TI  - Effects of centrally acting antihypertensive drugs on the microcirculation of
      spontaneously hypertensive rats.
AB  - We investigated the acute effects of centrally acting antihypertensive drugs on
      the microcirculation of pentobarbital-anesthetized spontaneously hypertensive
      rats (SHR). The effects of the sympatho-inhibitory agents clonidine and
      rilmenidine, known to activate both alpha2-adrenoceptors and nonadrenergic I1
      imidazoline binding sites (I1BS) in the central nervous system, were compared to
      those of dicyclopropylmethyl-(4,5-dimethyl-4,5-dihydro-3H-pyrrol-2-yl)-amine
      hydrochloride (LNP 509), which selectively binds to the I1BS. Terminal mesenteric
      arterioles were observed by intravital microscopy. Activation of the central
      sympathetic system with L-glutamate (125 microg, ic) induced marked
      vasoconstriction of the mesenteric microcirculation (27 +/- 3%; N = 6, P < 0.05).
      In contrast, the marked hypotensive and bradycardic effects elicited by
      intracisternal injection of clonidine (1 microg), rilmenidine (7 microg) and LNP
      509 (60 microg) were accompanied by significant increases in arteriolar diameter
      (12 +/- 1, 25 +/- 10 and 21 +/- 4%, respectively; N = 6, P < 0.05). The
      vasodilating effects of rilmenidine and LNP 509 were two-fold higher than those
      of clonidine, although they induced an identical hypotensive effect. Central
      sympathetic inhibition elicited by baclofen (1 microg, ic), a GABA B receptor
      agonist, also resulted in vasodilation of the SHR microvessels. The acute
      administration of clonidine, rilmenidine and LNP 509 also induced a significant
      decrease of cardiac output, whereas a decrease in systemic vascular resistance
      was observed only after rilmenidine and LNP 509. We conclude that the
      normalization of blood pressure in SHR induced by centrally acting
      antihypertensive agents is paralleled by important vasodilation of the mesenteric
      microcirculation. This effect is more pronounced with substances acting
      preferentially (rilmenidine) or exclusively (LNP 509) upon I1BS than with those
      presenting important alpha2-adrenergic activity (clonidine).

PMID- 15448877
TI  - Effect of the aerobic capacity on the validity of the anaerobic threshold for
      determination of the maximal lactate steady state in cycling.
AB  - The maximal lactate steady state (MLSS) is the highest blood lactate
      concentration that can be identified as maintaining a steady state during a
      prolonged submaximal constant workload. The objective of the present study was to
      analyze the influence of the aerobic capacity on the validity of anaerobic
      threshold (AT) to estimate the exercise intensity at MLSS (MLSS intensity) during
      cycling. Ten untrained males (UC) and 9 male endurance cyclists (EC) matched for
      age, weight and height performed one incremental maximal load test to determine
      AT and two to four 30-min constant submaximal load tests on a mechanically braked
      cycle ergometer to determine MLSS and MLSS intensity. AT was determined as the
      intensity corresponding to 3.5 mM blood lactate. MLSS intensity was defined as
      the highest workload at which blood lactate concentration did not increase by
      more than 1 mM between minutes 10 and 30 of the constant workload. MLSS intensity
      (EC = 282.1 +/- 23.8 W; UC = 180.2 +/- 24.5 W) and AT (EC = 274.8 +/- 24.9 W; UC
      = 187.2 +/- 28.0 W) were significantly higher in trained group. However, there
      was no significant difference in MLSS between EC (5.0 +/- 1.2 mM) and UC (4.9 +/-
      1.7 mM). The MLSS intensity and AT were not different and significantly
      correlated in both groups (EC: r = 0.77; UC: r = 0.81). We conclude that MLSS and
      the validity of AT to estimate MLSS intensity during cycling, analyzed in a cross
      sectional design (trained x sedentary), do not depend on the aerobic capacity.

PMID- 15448878
TI  - Cardiovascular responses to locomotor activity and feeding in unrestrained three
      toed sloths, Bradypus variegatus.
AB  - Heart rate (HR) and systolic (SBP), diastolic (DBP) and mean (MBP) blood pressure
      were recorded by biotelemetry in nine conscious unrestrained sloths for 1 min
      every 15 min over a 24-h period. The animals were allowed to freely move in an
      acoustically isolated and temperature-controlled (24 +/- 1 degree C) experimental
      room with light-dark cycle (12/12 h). Behavior was closely monitored through a
      unidirectional visor and classified as resting (sitting or suspended), feeding
      (chewing and swallowing embauba leaves, Cecropia adenops), or locomotor activity
      around the tree trunk or on the room floor. Locomotor activity caused
      statistically significant increases in SBP (+8%, from 121 +/- 22 to 131 +/- 18
      mmHg), DBP (+7%, from 86 +/- 17 to 92 +/- 10 mmHg), MBP (+8%, from 97 +/- 19 to
      105 +/- 12 mmHg), and HR (+14%, from 84 +/- 15 to 96 +/- 15 bpm) compared to
      resting values, indicating a possible major influence of the autonomic nervous
      system on the modulation of cardiac function during this behavior. During
      feeding, the increase in blood pressure was even higher (SBP +27%, from 119 +/-
      21 to 151 +/- 21 mmHg; DBP +21%, from 85 +/- 16 to 103 +/- 15 mmHg; MBP +24%,
      from 96 +/- 17 to 119 +/- 17 mmHg), while HR remained at 14% (from 84 +/- 15 to
      96 +/- 10 bpm) above resting values. The proportionally greater increase in blood
      pressure than in HR during feeding suggests an increase in peripheral vascular
      resistance as part of the overall response to this behavior.

PMID- 15448879
TI  - Myocardial contractility of the isovolumetrically beating isolated rat heart.
AB  - Several indexes of myocardial contractility have been proposed to assess
      ventricular function in the isovolumetrically beating isolated heart. However,
      the conclusions reached on the basis of these indexes may be influenced by
      ventricular geometry rather than contractility itself. The objective of the
      present study was to assess the performance of widely used contractility indexes
      in the isovolumetrically beating isolated heart in two experimental models of
      hypertrophy, the spontaneously hypertensive rat (SHR) and infrarenal aortocava
      fistula. Compared to normotensive controls (N = 8), SHRs with concentric
      hypertrophy (N = 10) presented increased maximum rate of ventricular pressure
      rise (3875 +/- 526 vs 2555 +/- 359 mmHg/s, P < 0.05) and peak of isovolumetric
      pressure (187 +/- 11 vs 152 +/- 11 mmHg, P < 0.05), and decreased developed
      stress (123 +/- 20 vs 152 +/- 26 g/cm(2), P < 0.05) and slope of stress-strain
      relationship (4.9 +/- 0.42 vs 6.6 +/- 0.77 g/cm(2)/%). Compared with controls (N
      = 11), rats with volume overload-induced eccentric hypertrophy (N = 16) presented
      increased developed stress (157 +/- 38 vs 124 +/- 22 g/cm(2), P < 0.05) and slope
      of stress-strain relationship (9 +/- 2 vs 7 +/- 1 g/cm(2)/%, P < 0.05), and
      decreased maximum rate of ventricular pressure rise(2746 +/- 382 vs 3319 +/- 352
      mmHg, P < 0.05) and peak of isovolumetric pressure (115 +/- 14 vs 165 +/- 13
      mmHg/s, P < 0.05). The results suggested that indexes of myocardial contractility
      used in experimental studies may present opposite results in the same heart and
      may be influenced by ventricular geometry. We concluded that several indexes
      should be taken into account for proper evaluation of contractile state, in the
      isovolumetrically beating isolated heart.

PMID- 15448880
TI  - Cholinergic-opioidergic interaction in the central amygdala induces
      antinociception in the guinea pig.
AB  - Several studies have demonstrated the involvement of the central nucleus of the
      amygdala (CEA) in the modulation of defensive behavior and in antinociceptive
      regulation. In a previous study, we demonstrated the existence of a cholinergic
      opioidergic interaction in the CEA, modulating the defensive response of tonic
      immobility in guinea pigs. In the present study, we investigated a similar
      interaction in the CEA, but now involved in the regulation of the nociceptive
      response. Microinjection of carbachol (2.7 nmol) and morphine (2.2 nmol) into the
      CEA promoted antinociception up to 45 min after microinjection in guinea pigs as
      determined by a decrease in the vocalization index in the vocalization test. This
      test consists of the application of a peripheral noxious stimulus (electric shock
      into the subcutaneous region of the thigh) that provokes the emission of a
      vocalization response by the animal. Furthermore, the present results
      demonstrated that the antinociceptive effect of carbachol (2.7 nmol; N = 10) was
      blocked by previous administration of atropine (0.7 nmol; N = 7) or naloxone (1.3
      nmol; N = 7) into the same site. In addition, the decrease in the vocalization
      index induced by the microinjection of morphine (2.2 nmol; N = 9) into the CEA
      was prevented by pretreatment with naloxone (1.3 nmol; N = 11). All sites of
      injection were confirmed by histology. These results indicate the involvement of
      the cholinergic and opioidergic systems of the CEA in the modulation of
      antinociception in guinea pigs. In addition, the present study suggests that
      cholinergic transmission may activate the release of endorphins/enkephalins from
      interneurons of the CEA, resulting in antinociception.

PMID- 15448881
TI  - Glutamatergic neurotransmission modulates hypoxia-induced hyperventilation but
      not anapyrexia.
AB  - The interaction between pulmonary ventilation (V E) and body temperature (Tb) is
      essential for O2 delivery to match metabolic rate under varying states of
      metabolic demand. Hypoxia causes hyperventilation and anapyrexia (a regulated
      drop in Tb), but the neurotransmitters responsible for this interaction are not
      well known. Since L-glutamate is released centrally in response to peripheral
      chemoreceptor stimulation and glutamatergic receptors are spread in the central
      nervous system we tested the hypothesis that central L-glutamate mediates the
      ventilatory and thermal responses to hypoxia. We measured V E and Tb in 40 adult
      male Wistar rats (270 to 300 g) before and after intracerebroventricular
      injection of kynurenic acid (KYN, an ionotropic glutamatergic receptor
      antagonist), alpha-methyl-4-carboxyphenylglycine (MCPG, a metabotropic
      glutamatergic receptor antagonist) or vehicle (saline), followed by a 1-h period
      of hypoxia (7% inspired O2) or normoxia (humidified room air). Under normoxia,
      KYN (N = 5) or MCPG (N = 8) treatment did not affect V E or Tb compared to saline
      (N = 6). KYN and MCPG injection caused a decrease in hypoxia-induced
      hyperventilation (595 +/- 49 for KYN, N = 7 and 525 +/- 84 ml kg-1 min-1 for
      MCPG, N = 6; P < 0.05) but did not affect anapyrexia (35.3 +/- 0.2 for KYN and
      34.7 +/- 0.4 masculine C for MCPG) compared to saline (912 +/- 110 ml kg-1 min-1
      and 34.8 +/- 0.2 masculine C, N = 8). We conclude that glutamatergic receptors
      are involved in hypoxic hyperventilation but do not affect anapyrexia, indicating
      that L-glutamate is not a common mediator of this interaction.

PMID- 15448882
TI  - [Guidelines of chronic coronary disease: stable angina].

PMID- 15448883
TI  - Quality of life assessments in women operated on by tension-free vaginal tape
      (TVT).
AB  - The aim of the study was to evaluate quality of life (QOL) prospectively in women
      who undergo tension-free vaginal tape (TVT) operation for stress urinary
      incontinence. Sixty-six women who completed QOL questionnaires and a 2-year
      follow-up examination were included. Improvement of health-related QOL was
      assessed by the Incontinence Impact Questionnaire-7 (IIQ-7), the Urogenital
      Distress Inventory-6 (UDI-6), and two questions regarding patient satisfaction
      and de novo urge incontinence. Prior to surgery, patients complained most of
      stress symptoms followed by physical activities and emotional health.
      Postoperatively IIQ-7 and UDI-6 as a whole and all seven domains improved
      significantly (p<0.001). Scores of IIQ-7, UDI-6, and seven domains did not differ
      between the adult and the elderly groups. Of the patients 88% were much satisfied
      or satisfied with surgical outcomes. Incidence of de novo urge incontinence was
      12%. It is concluded that the TVT procedure significantly improved health-related
      quality of life.

PMID- 15448884
TI  - Effects of voluntary pelvic floor contraction and relaxation on the urethral
      closure pressure.
AB  - The aim of this study was to assess the effects of voluntary pelvic floor
      contraction and voluntary pelvic floor relaxation on the urethral closure
      pressure at rest. In 104 consecutive women, three urethral pressure profiles were
      performed: standard profile at rest, with voluntary pelvic floor contraction and
      with voluntary pelvic floor relaxation. A low-pressure urethra was defined as a
      maximum urethral closure pressure of < or =20 cmH(2)O. The age ranged between 24
      and 82 years. The maximum urethral closure pressure at rest was significantly
      augmented during pelvic floor contraction (mean: 18 cmH(2)O). Compared with the
      first profile, it decreased significantly with pelvic floor relaxation (mean
      decrement: 8 cmH(2)O). A low-pressure urethra was detected in 5 women during the
      first profile and in a further 11 during pelvic floor relaxation. Because of the
      significant influence of pelvic floor activity on the urethral closure pressure
      at rest, the scientific and clinical credibility of urethral pressure
      measurements remain questionable.

PMID- 15448885
TI  - The now and the not yet of pelvic floor dysfunction.

PMID- 15448886
TI  - Knee arthroplasty for spontaneous osteonecrosis of the knee: unicompartimental vs
      bicompartimental knee arthroplasty.
AB  - Spontaneous osteonecrosis of the knee (SON) is an osteonecrosis that mainly
      affects the medial femoral condyle. In endstage SON, knee arthroplasty is the
      therapy of choice. Because of the unicompartimental nature of the knee,
      unicondylar knee arthroplasty is considered an ideal implant for treatment of
      this condition. The purpose of this study was to prove that the long-term results
      of unicondylar implants are better than the results of bicondylar implants for
      the treatment of SON. All patients treated for SON between 1984 and 2000 have
      been recorded. Two groups were formed according to the implant used. In all
      patients the preoperative radiograph was analyzed according to stage and size of
      the osteonecrotic lesion and the osteoarthritic changes. Postoperatively, the
      Knee Society Score and the radiograph were recorded. Thirty-nine patients were
      included in this study, of which 23 patients were treated by a unicondylar
      implant and 16 by a bicondylar implant. On a short-term basis, unicondylar
      implants had better clinical results; however, on a long-term basis bicondylar
      implants were better. In comparison, only unicondylar implants had to be revised.
      Radiolucency lines were mainly observed in patients with unicondylar impants and
      large areas of osteonecrosis. Our long-term results suggest that patients with
      SON are better treated by bicondylar implants. The reasons for the higher failure
      rate for unicondylar implants are poor bone stock and secondary arthritic
      changes.

PMID- 15448887
TI  - Hydrochloric acid-induced lung injury: effects of early partial liquid
      ventilation on survival rate, gas exchange, and pulmonary neutrophil
      accumulation.
AB  - OBJECTIVE: Partial liquid ventilation can improve respiratory functions in acid
      induced lung injury. We studied the effects of the interval between induction of
      injury and initiation of partial liquid ventilation on survival, gas exchange,
      and pulmonary neutrophil accumulation. MATERIAL AND METHODS: Anesthetized rats
      were randomly assigned to one of five groups ( n = 6 per group). Group 1 served
      as the control group, in the other groups an extended lung injury was induced by
      intratracheal instillation of hydrochloric acid. Whereas lungs of group 2 were
      gas-ventilated, group 3 received an early partial liquid ventilation (5 min after
      acid instillation) and group 4 a delayed partial liquid ventilation (30 min after
      acid instillation, 5 ml/kg perfluorocarbon). Group 5 received an additional
      continuous perfluorocarbon application of 5 ml x kg(-1) x h(-1) (30 min after
      acid instillation). Blood gases were measured with an intravascular blood gas
      sensor. RESULTS: Acid instillation resulted in a marked decrease in PO(2)-values
      within 30 min (from 481+/-37 mmHg to 128+/-71 mmHg, FiO(2) 1.0). Survival rate of
      the study period (12 h) was higher with early partial liquid ventilation. We
      observed no differences between groups in peak PO(2)-values during treatment.
      Histopathological examination, however, showed less pulmonary neutrophil
      accumulation in lungs of the early partial liquid ventilation group when compared
      to the delayed partial liquid ventilation group. CONCLUSIONS: Our results suggest
      that early partial liquid ventilation increases survival after extended acid
      induced lung injury. While effects on arterial oxygenation appear not to predict
      acute survival we observed less intrapulmonary neutrophil accumulation with early
      partial liquid ventilation.

PMID- 15448888
TI  - Initial distribution volume of glucose as noninvasive indicator of cardiac
      preload: comparison with intrathoracic blood volume.
AB  - OBJECTIVE: To analyze the correlation between initial distribution volume of
      glucose (IDVGI) and intrathoracic blood volume measured by single indicator
      dilution technique. DESIGN AND SETTING: Prospective clinical study conducted in
      the intensive care unit of a university hospital. PATIENTS AND METHODS: We
      enrolled 20 consecutive adult patients requiring hemodynamic monitoring with
      arterial pulse contour analysis system (PiCCO) and without any underlying
      pathology inducing generalized protein capillary leakage and/or marked peripheral
      edema. Cardiac output, intrathoracic blood volume, extravascular lung water were
      recorded. IDVGI was measured once per day for the first 5 days after PiCCO
      positioning by administering a bolus of 25 ml 20% glucose (5 g) over 30 s through
      a central venous catheter. The relationship between IDVGI and other variables was
      studied by regression analysis. Receiver operating characteristic curves were
      used to study the relationship between changes in IDVGI and changes in cardiac
      index, intrathoracic blood volume, and central venous pressure. RESULTS: A good
      linear correlation was obtained between intrathoracic blood volume and IDVGI (
      R(2)=0.79). Receiver operating characteristic curve analysis showed a good
      ability of initial distribution volume of glucose variations to reflect cardiac
      index variations. CONCLUSIONS: Our results indicate that IDVGI can serve as
      noninvasive indicator of cardiac preload.

PMID- 15448889
TI  - Blood flow reductions during continuous renal replacement therapy and circuit
      life.
AB  - OBJECTIVE: Reductions in blood flow rate may occur undetected during peristaltic
      pumping of blood through continuous renal replacement therapy circuits. We
      investigated whether undetected reductions in blood flow rate occur during
      continuous veno-venous haemofiltration, and whether they are correlated with
      filter life. PATIENTS: Twelve patients receiving continuous veno-venous
      haemofiltration in the intensive care unit of a tertiary hospital. METHODS:
      Extracorporeal circuit blood flow during haemofiltration was continuously
      monitored utilizing a miniature ultrasound Doppler device. Otherwise undetected
      blood flow reductions were identified at severity levels of between 20% and 100%
      less than the set diastolic flow rate (83 ml/min). Information on anticoagulation
      status was simultaneously obtained. The frequency and severity of blood flow
      reductions were recorded, and the correlation with filter life was determined.
      MEASUREMENTS AND RESULTS: The duration of filter life ranged from 1.5 to 53 h,
      with a mean functional life of 19.62+/-16.32 h. There were 314 episodes of blood
      flow reduction during the 525 h of monitoring (0.59 episodes/h). There was a
      significant inverse relationship between the number of medium-level blood flow
      reductions and filter life. This correlation was much stronger than that between
      APTT and filter life. CONCLUSIONS: Undetected blood flow reductions occur during
      continuous veno-venous haemofiltration. Such reductions are frequent, and when
      sufficiently severe appear to be correlated with filter life more strongly than
      the blood coagulation variables typically used to monitor adequacy of
      anticoagulation and promote filter longevity.

PMID- 15448890
TI  - Epidural analgesia in sepsis: too early to judge a new concept.

PMID- 15448891
TI  - Matching total body oxygen consumption and delivery: a crucial objective?
AB  - The strength of the rationale for incorporating total body oxygen consumption
      (VO(2)) and delivery (DO(2)) into our decision making strategies contrasts with
      the absence of demonstrated benefits of bedside calculations in clinical
      practice. This situation mandates a careful reappraisal of the theoretical
      limitations of bedside calculations of DO(2) and VO(2), including a re-evaluation
      of the clinical situations in which these calculations are valid. Three levels of
      complexity can be distinguished when analysing a patient's hemodynamic status: 1)
      simple cases where investigations can be limited to clinical monitoring,
      including lactate changes over time; 2) intermediate situations requiring
      invasive investigations in which continuous monitoring of VO(2)-related variables
      such as cardiac output and mixed venous oxygen saturation often provide enough
      information to guide clinical decision; and 3) complex situations where
      assessment of VO(2) and VO(2)/DO(2) analysis might be recommended. Although
      studies that support such recommendations are limited they are based on a widely
      accepted physiological model. VO(2) and DO(2) analysis is also limited by
      theoretical and technical difficulties. In this article, we discuss the validity
      of these limitations in the bedside assessment of VO(2) and DO(2), and review
      data supporting the use of VO(2)/DO(2) analysis in the clinical evaluation of
      complex cases.

PMID- 15448892
TI  - A law for end of life care in France?

PMID- 15448893
TI  - An analytical formula to estimate confidence interval of QTL location with a
      saturated genetic map as a function of experimental design.
AB  - Analytical formulae are derived for the confidence interval for location of a
      quantitative trait locus (QTL) using a saturated genetic map, as a function of
      the experimental design, the QTL allele substitution effect, and the number of
      individuals genotyped and phenotyped. The formulae are derived assuming evenly
      spaced recombination events, rather than the actual unevenly spaced distribution.
      The formulae are useful for determining desired sample size when designing a wide
      variety of QTL mapping experiments, and for evaluating a priori the potential of
      a given mapping population for defining the location of a QTL. The formulae do
      not take into account the finite number of recombination events in a given
      sample.

PMID- 15448894
TI  - Cross-species transferability and mapping of genomic and cDNA SSRs in pines.
AB  - Two unigene datasets of Pinus taeda and Pinus pinaster were screened to detect di
      , tri- and tetranucleotide repeated motifs using the SSRIT script. A total of 419
      simple sequence repeats (SSRs) were identified, from which only 12.8% overlapped
      between the two sets. The position of the SSRs within their coding sequences were
      predicted using FrameD. Trinucleotides appeared to be the most abundant repeated
      motif (63 and 51% in P. taeda and P. pinaster, respectively) and tended to be
      found within translated regions (76% in both species), whereas dinucleotide
      repeats were preferentially found within the 5'- and 3'-untranslated regions (75
      and 65%, respectively). Fifty-three primer pairs amplifying a single PCR fragment
      in the source species (mainly P. taeda), were tested for amplification in six
      other pine species. The amplification rate with other pine species was high and
      corresponded with the phylogenetic distance between species, varying from 64.6%
      in P. canariensis to 94.2% in P. radiata. Genomic SSRs were found to be less
      transferable; 58 of the 107 primer pairs (i.e. 54%) derived from P. radiata
      amplified a single fragment in P. pinaster. Nine cDNA-SSRs were located to their
      chromosomes in two P. pinaster linkage maps. The level of polymorphism of these
      cDNA-SSRs was compared to that of previously and newly developed genomic-SSRs.
      Overall, genomic SSRs tend to perform better in terms of heterozygosity and
      number of alleles. This study suggests that useful SSR markers can be developed
      from pine ESTs.

PMID- 15448895
TI  - Comparative mapping of wheat chromosome 1AS which contains the tiller inhibition
      gene (tin) with rice chromosome 5S.
AB  - The capacity to tiller is a key factor that determines plant architecture. Using
      molecular markers, a single major gene reducing tiller number, formally named the
      tiller inhibition gene ( tin), was mapped to the short arm of chromosome 1A in
      wheat. We identified a tightly linked microsatellite marker ( Xgwm136) that may
      be useful in future marker-assisted selection. The tin gene was mapped to the
      distal deletion bin of chromosome 1AS (FLM value 0.86) and wheat ESTs which were
      previously mapped to the same deletion bin were used to identify 18 closely
      related sequences in the syntenic region of rice chromosome 5. For a subset of
      wheat ESTs that detected flanking markers for tin, we identified closely related
      sequences within the most distal 300 kb of rice chromosome 5S. The synteny
      between the distal chromosome ends of wheat 1AS and rice 5S appeared to be
      disrupted at the hairy glume locus and seed storage protein loci. We compared map
      position of tin with other reduced tillering mutants characterised in other
      cereals to identify possible orthologous genes.

PMID- 15448896
TI  - Two allelic or tightly linked genetic factors at the PLRV.4 locus on potato
      chromosome XI control resistance to potato leafroll virus accumulation.
AB  - A novel locus for potato resistance to potato leafroll virus (PLRV) was
      characterized by inheritance studies and molecular mapping. The diploid parental
      clone DW 91-1187 was resistant to PLRV accumulation in both inoculated plants and
      their tuber progeny. The resistance to PLRV accumulation present in DW 91-1187
      was not transmitted to any F1 offspring when crossed with a PLRV susceptible
      clone. Instead, one half of the F1 individuals exhibited undetectable amounts of
      PLRV as determined by ELISA during the primary infection assay, but accumulated
      PLRV in their tuber progeny plants. The other half was clearly infected both in
      the inoculated and tuber-born plants. The inheritance of resistance to PLRV
      accumulation may be explained by a model of two complementary alleles of a single
      gene ( PLRV.4) or by two complementary genes that are closely linked in repulsion
      phase. Random amplified polymorphic DNA (RAPD) and inter-simple sequence repeat
      (ISSR) markers linked to the PLRV.4 locus were selected. The two complementary
      factors were closely linked in coupling phase to the alternative alleles
      UBC864(600) and UBC864(800) of DNA marker UBC864. These markers may be used for
      marker-assisted selection of genotypes having both factors for resistance to PLRV
      accumulation. The PLRV.4 locus was mapped to a central position on linkage group
      XI of the potato molecular map, where no resistance locus has been mapped
      previously.

PMID- 15448897
TI  - Determination and evaluation of the sequence and textural effects of the
      puroindoline a and puroindoline b genes in a population of synthetic hexaploid
      wheat.
AB  - Aegilops tauschii (2 n=2 x=14, DD) is a rich source of genetic variability for
      hexaploid wheat ( Triticum aestivum, 2 n=6 x=42, AABBDD) improvement. This
      variability can be accessed through utilizing synthetic hexaploid wheat lines,
      which contain genomes from Ae. tauschii and T. turgidum (2 n=4 x=28, AABB).
      Numerous desirable characteristics can and have been introgressed into common
      hexaploid wheat with this germplasm. In this work, the genetic variability in the
      two puroindoline genes (a and b) contained on the D genome, and the relationship
      that sequence polymorphisms in these genes have on endosperm texture among a
      population of 75 CIMMYT synthetic hexaploid accessions is described. Kernel
      texture was evaluated using the single kernel characterization system (SKCS).
      Kernel texture differed significantly ( P<or=0.0001) among the synthetic
      hexaploid accessions (range 2.6-40.9) and the parent types, durum or Ae.
      tauschii. The interaction term between parent types was also a significant effect
      ( P<or=0.0001). In addition to the 'wild-type' protein sequences of the
      puroindoline genes (those present in 'Chinese Spring' and all other soft wheats),
      three other translated sequences were identified in puroindoline a and two others
      in puroindoline b. These protein sequences were associated with significantly (
      P<or=0.0001) softer endosperm textures than the wild-type protein sequences. As
      the softer alleles are expressed in a hexaploid background, they are immediately
      available to wheat breeding programs.

PMID- 15448898
TI  - Co-transformation using a negative selectable marker gene for the production of
      selectable marker gene-free transgenic plants.
AB  - A negative selectable marker gene, codA, was successfully co-transformed with a
      GUS reporter gene to develop selectable marker gene-free transgenic plants. The
      pNC binary vector contained a T-DNA harboring the codA gene next to the nptII
      gene, while a second binary vector, pHG, contained a GUS reporter gene. Tobacco
      plants ( Nicotiana tabacum cv. Samsun NN) were co-transformed via the mixture
      method with Agrobacterium tumefaciens LBA4404 strains harboring pNC and pHG,
      respectively. Seeds harvested from the co-transformants were sown on germination
      media containing 5-fluorocytosine (5-FC). Analysis of the progeny by GUS staining
      and PCR amplification revealed that all of the 5-FC-resistant R(1) plants were
      codA free, and that the codA gene segregated independently of the GUS gene.
      Because codA-free seedlings developed normally on 5-FC-containing medium, we
      suggest that co-transformation with negatively selectable markers is a viable
      method for the production of easily distinguished, selectable marker gene-free
      transgenic plants.

PMID- 15448899
TI  - QTL analysis of lodging resistance and related traits in Italian ryegrass (
      Lolium multiflorum Lam.).
AB  - Italian ryegrass ( Lolium multiflorum Lam.) is the most widely cultivated annual
      forage grass in Japan. Lodging damage reduces both harvested yield and forage
      quality. To identify the chromosomal regions controlling lodging resistance in
      Italian ryegrass, we analyzed seven quantitative characters--heading date, plant
      height, culm weight, culm diameter, culm strength, tiller number, and culm
      pushing resistance--and evaluated lodging scores in the field in a two-way pseudo
      testcross F1 population. Significant correlations between most combinations of
      the traits examined were found. Seventeen QTLs for all traits except culm weight
      were detected on six of seven linkage groups by simple interval mapping using
      cross-pollination (CP) algorithm, and 33 independent QTLs were also detected by
      composite interval mapping from both male and female parental linkage maps. In
      addition, up to 18 QTLs for lodging scores evaluated at nine different times were
      detected on all linkage groups. The flanking markers of those QTLs will serve as
      a useful tool for marker-assisted selection of lodging resistance in Italian
      ryegrass.

PMID- 15448900
TI  - Durum wheat as a candidate for the unknown female progenitor of bread wheat: an
      empirical study with a highly fertile F1 hybrid with Aegilops tauschii Coss.
AB  - Hexaploid bread wheat was derived from a hybrid cross between a cultivated form
      of tetraploid Triticum wheat (female progenitor) and a wild diploid species,
      Aegilops tauschii Coss. (male progenitor). This cross produced a fertile triploid
      F1 hybrid that set hexaploid seeds. The identity of the female progenitor is
      unknown, but various cultivated tetraploid Triticum wheats exist today. Genetic
      and archaeological evidence suggests that durum wheat ( T. turgidum ssp. durum)
      may be the female progenitor. In previous studies, however, F1 hybrids of durum
      wheat crossed with Ae. tauschii consistently had low levels of fertility. To
      establish an empirical basis for the theory of durum wheat being the female
      progenitor of bread wheat, we crossed a durum wheat cultivar that carries a gene
      for meiotic restitution with a line of Ae. tauschii. F1 hybrids were produced
      without using embryo rescue techniques. These triploid F1 hybrids were highly
      fertile and spontaneously set hexaploid F2 seeds at the average selfed seedset
      rate of 51.5%. To the best of our knowledge, this is the first example of the
      production of highly fertile F1 hybrids between durum wheat and Ae. tauschii. The
      F1 and F2 hybrids are both similar morphologically to bread wheat and have
      vigorous growth habits. Cytological analyses of F1 male gametogenesis showed that
      meiotic restitution is responsible for the high fertility of the triploid F1
      hybrids. The implications of these findings for the origin of bread wheat are
      discussed.

PMID- 15448901
TI  - [Tissue engineering in urology. Status in Germany in 2004].

PMID- 15448902
TI  - [Bioartificial materials in urology].
AB  - The scope of our research is the development of polymer-based bioabsorbable
      stents for urologic applications and in vitro testing of tissue reactions of
      cultured ureteral and urethral segments induced by implanted polymer stent
      prototypes. For these purposes a tissue cultivation model was developed using
      selected techniques of tissue engineering. Essential advantages of degradable
      over nondegradable urethral stents are elimination of the adverse extraction of
      epithelialized stents and the potential for recovery of organ-specific
      functionality. Moreover, the biocompatibility of a degradable urethral stent
      could potentially reduce the risk of restenosis due to hyperplasia and could be
      used, even repeatedly, for the treatment of a number of subvesical obstructions.
      For the treatment of tumor-induced strictures, application of degradable polymer
      stents coated with cytostatic drugs may be possible. The mechanical effect of the
      drug-loaded stent as a "place holder" could be complemented by adjuvant or
      palliative approaches such as local chemotherapy. We have developed and tested in
      vitro a degradable urethral stent incorporated with the model drug methotrexate
      for local drug delivery (LDD) by diffusion and during stent degradation.

PMID- 15448903
TI  - [Stress incontinence and mixed incontinence].
AB  - According to the new ICS classifications urinary incontinence is divided by
      symptomatic, clinical and urodynamic criteria. Urinary incontinence is a non life
      threatening condition, which may affect life quality a lot. Stress incontinence
      may present alone or may occur as mixed incontinence. The understanding of
      pathophysiological interactions is important to perform adequate diagnostics and
      start appropriate therapy. The patients should be informed about the wide
      spectrum of different conservative and surgical treatment options, their results
      and typical complications. Further randomised trials are necessary for critical
      evaluation of each treatment option.

PMID- 15448904
TI  - [Acellular matrix for functional reconstruction of the urogenital tract. Special
      form of "tissue engineering"?].
AB  - Organ substitution and reconstruction of the urogenital system still poses a
      problem regarding an adequate substitute. Usually non-organ-specific materials
      are used for reconstruction (bowl, buccal mucosa). This nonspecific tissue can
      cause side effects that result from the origin and the natural function.
      Different groups have shown that an acellular matrix graft in the urinary bladder
      and the urethra served as a scaffold for complete regeneration of all organ wall
      components and that this organ-specific regeneration simultaneously facilitates
      functional restitution. New approaches will presumably effect better regeneration
      after seeding the matrix with organ-specific cells (i.e., urothelial cells).
      Smaller studies on genital reconstructive surgery could show that vaginal
      substitution with an acellular matrix might be possible or that there could be a
      possible substitute for the tunica during surgical treatment of Peyronie's
      disease.

PMID- 15448905
TI  - [Tumor-like lesions].
AB  - Tumor-like bone lesions include various conditions of a non-neoplastic nature
      originating from or affecting the bone as solitary or sometimes multiple bone
      lesions. This review discusses the most important cystic tumor-like lesions, such
      as simple bone cyst, aneurysmal bone cyst, intraosseous ganglion, epidermoid cyst
      and subchondral cyst. MR is the most sensitive method of detection, and is the
      most accurate in depicting the extent of involvement of these lesions. MR signal
      characteristics may aid in differential diagnosis. Conventional radiographs are
      often more specific with respect to the underlying histopathology.

PMID- 15448906
TI  - [Whole body MRI -- vision or reality?].

PMID- 15448907
TI  - [Magnetic resonance angiography in the head-neck area].
AB  - Magnetic resonance angiography is a noninvasive method in vascular imaging using
      non-contrast-enhanced and contrast-enhanced techniques. The contrast media used
      in contrast-enhanced magnetic resonance angiography are different from the X-ray
      contrast me-dia and do not affect the thyroid gland or renal function. In
      detecting hypervascularized lesions in the head and neck, contrast-enhanced
      magnetic resonance angiography is the method of choice, which provides an
      acceptable quality in comparison to digital subtraction angiography. Future
      developments in magnetic resonance imaging techniques will cause a wider use of
      magnetic resonance angiography, especially in head and neck imaging. Digital
      subtraction angiography should therefore only be used in problem cases and for
      preoperative embolization.

PMID- 15448910
TI  - [Differential indications for atypical neuroleptics: Amisulprid, Clozapin,
      Olanzapin, Quetiapin und Risperidon. Results of a pilot study of prescription
      habits in psychiatric clinical usage in the BRD].
AB  - With the introduction of atypical neuroleptics, the therapy of schizophrenia has
      been improved by a group of antipsychotic substances characterized by better
      tolerability concerning extrapyramidal side effects and higher efficiency against
      negative symptoms. However, these atypical antipsychotics are not a homogeneous
      class of drugs but rather represent a group of substances with very different
      neurobiologic, pharmacologic, and clinical features. This fact and the growing
      variety of available atypical neuroleptics illustrate the difficulty in choosing
      the "right" antipsychotic drug for each patient. The aim of this investigation
      was to evaluate preliminary empirical data for possible differential indication
      of atypical neuroleptics by a questionnaire-based survey of 192 physicians in ten
      psychiatric hospitals active in the biological psychiatry work group of the
      German Federal Directors' Conference.

PMID- 15448911
TI  - [Management of iatrogenic lesions of the spinal accessory nerve].
AB  - Lesions of the spinal accessory nerve are usually iatrogenic, especially after
      lymph node extirpation on the neck. Between 1994 and 2003, 31 patients were
      operated on in the Neurosurgical Department of the University of Ulm for
      iatrogenic lesions of the XIth cranial nerve. Of 31 patients, 22 had undergone a
      previous lymph node extirpation, 2 had been injured during a selective peripheral
      denervation for spasmodic torticollis, and the other 7 patients by different
      causes. The neurosurgical intervention was performed 0-19 months after trauma
      (mean 7.2 months). All patients showed paresis/atrophy of the trapezius muscle,
      and the abduction of the shoulder was markedly reduced. Additional neck and/or
      shoulder pain was present in 29 of 31 cases. In seven cases, the nerve was
      compressed by scar tissue and subsequently treated by external neurolysis. Ten
      patients underwent an end-to-end anastomosis; autologous sural nerve grafting was
      necessary in 13 cases. After a mean follow-up of 12.6 months, 7 of 31 patients
      completely recovered. Of 31 patients, 19 experienced partial relief of pain and
      weakness. Only five patients remained unchanged. The clinical findings after
      autologous nerve grafting, end-to-end reconstruction, or external neurolysis did
      not show any significant differences. Microsurgical reconstruction of iatrogenic
      injury of the spinal accessory nerve is very promising if the interval between
      trauma and surgical revision is less than 6 months. Up to 12 months, partial
      recovery can be achieved. Outcome after longer delay is unsatisfactory.

PMID- 15448912
TI  - [Treatment of sialorrhea with botulinum toxin: an overview].
AB  - Hypersalivation (sialorrhea) is a common complaint of patients with
      neurodegenerative disorders such as Parkinson's disease or amyotrophic lateral
      sclerosis and a frequently disabling side effect of atypical antipsychotic drugs.
      Conventional treatment including oral anticholinergic or antihistamine medication
      is often limited by adverse effects and lack of efficacy. Over the past few
      years, several studies reported decreased drooling after injections of botulinum
      toxin into the salivary glands. This review describes the current state of
      treatment of sialorrhea with botulinum toxin.

PMID- 15448913
TI  - [Pharmacological strategies for clozapine-induced hypersalivation: treatment with
      botulinum toxin B in one patient and review of the literature].
AB  - Hypersalivation is frequently observed in patients treated with clozapine.
      Current strategies to counteract sialorrhea include the introduction of
      antimuscarinergic (anticholinergic) and alpha(2)-agonistic treatment. However,
      the use of these substances is limited in part by lack of efficacy and by adverse
      side effects. In cases of intractable sialorrhea, the application of botulinum
      toxin may be a new and safe therapeutic option. We here present an overview on
      current treatment strategies for sialorrhea and describe a patient who received
      botulinum toxin B for clozapine-induced hypersalivation.

PMID- 15448914
TI  - [Statins for treatment of CNS diseases. Status report from research and clinical
      practice].
AB  - 3-Hydroxy-3-methyglutaryl coenzyme A (HMG-CoA) reductase inhibitors, "statins,"
      are widely used oral cholesterol-lowering drugs. Statins competitively inhibit
      HMG-CoA reductase, the enzyme that catalyzes conversion of HMG-CoA to L
      mevalonate, a key intermediate in cholesterol synthesis. Certain metabolites of L
      mevalonate are also involved in posttranslational modifications of specific
      proteins with cell proliferation and differentiation properties. Thus, statins
      have important biologic effects beyond their cholesterol-reducing properties.
      Here we discuss recent experimental and clinical data that may support a
      potential role for statins in the treatment of three central nervous system (CNS)
      neurological diseases: Multiple sclerosis (MS), Alzheimer's disease (AD), and
      ischemic stroke. Despite their considerable pathogenic differences, in animal
      models of these disorders statins have shown beneficial effects. In both stroke
      and AD cohort studies suggest a beneficial treatment effect in humans; in MS,
      results from small open-label studies look encouraging. Multicenter, randomized,
      placebo-controlled clinical trials are in the planning or recruiting stage to
      evaluate the therapeutic effects of statins in all three disorders.

PMID- 15448915
TI  - [Psychiatric disorders and the prognosis for criminal recidivism].
AB  - The risk for criminal recidivism of mentally ill offenders is, unlike the general
      risk of delinquency, not well established. The relationship between psychiatric
      diagnosis and criminal recidivism was examined in the context of the Munich
      project on risk assessment. A total of 185 offenders had been examined on the
      question of culpability between 1992 and 1993. Re-offenses committed before the
      end of 2001 were recorded according to the Federal Registry of court sentences
      (Bundeszentralregister); 38.8% of the total group recidivated. High rates of
      recidivism were observed for individuals with substance abuse (45.5%) and with
      personality disorders (46.6%). The combination of the two illnesses increased the
      rate for recidivism to 50%. For individuals with organic, affective and neurotic
      disorders the rates for recidivism were below the average. Rates of recidivism
      for schizophrenic offenders were slightly higher, if re-offenses in the state of
      inculpability were included. The HCR-20 predicted recidivism equally well for
      offenders with and without a psychiatric diagnosis. In both groups, individuals
      with HCR-20 scores above the mean recidivated more often and after shorter
      periods of time.

PMID- 15448916
TI  - [Eppendorf Schizophrenia Inventory (ESI) vs. Frankfurt Complaint Questionnaire
      (FCQ). Direct comparison in a clinical trial].
AB  - This study is the first to directly compare two clinical questionnaires which are
      both aimed at self-experienced cognitive dysfunctions of schizophrenia: Eppendorf
      Schizophrenia Inventory (ESI) and Frankfurt Complaint Questionnaire (FCQ).
      Evaluated were (a) diagnostic validity, (b) psychometric properties, (c) scale
      intercorrelations, and (d) factor analytic stability. Ad (a): schizophrenic
      subjects (n=36) show highly significant increases in the ESI scales and sum score
      when compared to other clinical groups (patients with depression, alcohol
      dependence, or obsessive-compulsive disorder, n>30, respectively); on the other
      hand, the FCQ yields no systematic group differences. Ad (b): mean of reliability
      coefficients (Cronbach alpha) of the ESI scales is r(tt)=0.86, mean of
      reliability coefficients of the FCQ scales is significantly lower. Ad (c): the
      mean intercorrelation between ESI and FCQ scales amounts to r(xy)=0.56 (minimum
      0.29, maximum 0.73), corresponding to an average shared variance of about 31%. Ad
      (d): factor analysis yielded an ESI factor and a FBF factor; one-way ANOVA with
      the factor scores confirms the diagnostic validity of the ESI. CONCLUSIONS: ESI
      and FCQ measure essentially different aspects of schizophrenic psychopathology.
      Regarding reliability and diagnostic validity, the ESI is superior to the FCQ.

PMID- 15448917
TI  - [Temperament and character in persons with borderline personality disorder].
AB  - High comorbidity, suicidal ideation, difficult temperament, and character are key
      symptoms of persons with borderline personality disorder (BPD). We investigated
      478 persons, 40 of whom had a BPD according SCID-II, self-rating. Participants
      were examined with a semistructured interview and several self-rating
      questionnaires in their households. Taking the high comorbidity of persons with
      BPD into account, we compared the BPD group with four control groups with
      different axis 1 or personality disorders and one nonclinical group. Persons with
      BPD showed high comorbidity with affective, anxiety, and alcohol use disorders.
      With respect to suicidality, 75% reported that they wish to be dead at least
      sometimes, and about one-third said that they had already attempted suicide.
      Regarding temperament and character dimensions, our analyses revealed higher
      novelty seeking for persons with BPD compared to participants without BPD,
      although this difference was primarily attributable to males with BPD.
      Additionally, participants with BPD reported higher harm avoidance compared to
      control groups, while this was more distinctive for females. Finally, we found
      that persons with BPD had very low levels of self-directedness. This effect was
      independent from gender and was found in all group comparisons. Therapy of BPD
      should take into account high comorbidity and suicidality of patients. Moreover,
      our results show that low self-directedness seems to be specific for persons with
      BPD. Therefore, therapy must address those deficits by focusing on skills
      training as well as on aspects of maturation.

PMID- 15448918
TI  - [Electroconvulsive therapy at the Department of Psychiatry and Psychotherapy,
      University of Munich. Development during the years 1995-2002].
AB  - BACKGROUND: So far, electroconvulsive therapy (ECT) has been proven to be a
      reliable and the most effective somatic treatment of depression or schizophrenia.
      This holds especially true for disturbances, which are refractory to
      pharmacological treatments. PATIENTS AND METHODS: We evaluated 4803 treatments in
      445 patients. Main outcome criteria were efficacy and tolerability of treatment.
      Moreover, prospectively recorded neurophysiological parameters that might
      influence treatment outcome and treatment modalities and were assessed in a
      retrospective study design. RESULTS: During the last 7 years developmental
      changes show an increasing call for ECT treatment. Despite not being able to
      satisfy all demands the number of treatments more than doubled during the time
      period investigated. According to the latest scientific knowledge, especially in
      unipolar ECT, higher stimulation energy has been used to provide better treatment
      efficacy. Nevertheless, this was accompanied by a lower incidence of cognitive
      side effects. Due to the better tolerability of the treatment and the prospective
      neurophysiological indices, it appears that treatment quality has improved in
      recent years. Overall treatment efficacy was not improved, but could be
      maintained on a stable high level. This is presumably due to a stronger negative
      selection of patients with more pharmacotherapy-refractory disturbances.
      CONCLUSION: ECT still represents an important option in the treatment of therapy
      resistant depression and schizophrenia despite recent progress in
      neuropsychopharmacology.

PMID- 15448919
TI  - [Who comes from where and who goes where? Treatment methods for psychiatric
      inpatients].
AB  - Based on data of the psychiatric basic documentation of 4066 patients, predictors
      of type of referral as well as outpatient aftercare were analyzed by means of
      logistic regression analyses. Of the patients, 25.7% were admitted without any
      referral, 18.4% were referred by a general practitioner, and 9.8% by a
      psychiatrist in private practice. Patients referred by a general practitioner
      suffered more frequently from an affective disorder or schizophrenia and were
      residents of senior citizen homes. Inpatients sent by a psychiatrist were more
      often residents of sheltered homes, showed a present episode lasting more than 3
      months, and had undergone psychopharmacological pretreatment with an atypical
      antipsychotic or SSRI. Outpatient aftercare was recommended to 83.1% of
      inpatients: 49.4% by a general practitioner and 32.1% by a psychiatrist in
      private practice. Outpatient aftercare by a general practitioner was more
      frequent in the elderly and patients with addiction disorders. Referral by a
      psychiatrist in private practice as well as schizophrenia or an affective
      disorder led more often to outpatient aftercare by a psychiatrist. The small
      number of patients referred by general practitioners and psychiatrists in private
      practice has to become the focus of quality management.

PMID- 15448920
TI  - [Why do schizophrenic patients smoke?].
AB  - Patients suffering from schizophrenia are known to show an increased prevalence
      of nicotine addiction. The aim of this paper is to elucidate the relationship
      between schizophrenia and (chronic) use of nicotine. Nicotine seems to improve
      cognitive functions critically affected in schizophrenia, in particular sustained
      attention, focused attention, working memory, short-term memory, and recognition
      memory. Furthermore, several studies using evoked potentials (P50 paradigm) and
      prepulse inhibition of the acoustic startle reflex suggest that deficient
      preattentive information processing, a core feature of schizophrenia illness, is
      improved following treatment with nicotine. Smoking can also improve
      extrapyramidal secondary effects of antipsychotic medication and it induces
      cytochrome P4501A2, an enzyme system involved in the metabolism of several
      antipsychotics. There is substantial evidence that nicotine could be used by
      patients with schizophrenia as a "self-medication" to improve deficits in
      attention, cognition, and information processing and to reduce side effects of
      antipsychotic medication. Possible pharmacotherapeutic approaches for the
      regulation of abnormal neurotransmission at nicotinic acetylcholine receptors are
      discussed.

PMID- 15448921
TI  - [Depression in Hashimoto's encephalopathy. Successful treatment of a severe
      depressive episode with a glucocorticoid as an add-on therapy].
AB  - Characteristic clinical findings of Hashimoto's encephalopathy (HE) are stroke
      like episodes, epileptic seizures, myoclonus, psychosis, and progressive
      cognitive impairment. Diagnosis of HE is supported by elevated antithyroid
      antibodies, an abnormal EEG, and by good response to steroids. We report on a 74
      year-old female patient with a severe depressive episode who showed no treatment
      response to citalopram 40 mg/day and venlafaxine 150 mg/day. Diagnostic
      examination revealed an abnormal EEG, elevated thyroid peroxidase antibodies (TPO
      Ab), and older postinflammatory changes in thyroidal sonography. We diagnosed a
      depression in HE and began treatment with prednisolone 70 mg/day with stepwise
      dose reduction, continuing treatment with venlafaxine 150 mg/day. Within 4 weeks
      of treatment, the severe depressive episode disappeared as well as abnormal EEG.
      In addition, serum values of TPO-Ab decreased. In HE, depressive symptoms can
      possibly be seen in a subgroup of patients or in the early course of the disease.
      Diagnosis of HE should be included in diagnostic procedures in cases of therapy
      refractory depression because of a good response of HE to steroids.

PMID- 15448922
TI  - Isolation and characterization of mesophilic, oxalate-degrading Streptomyces from
      plant rhizosphere and forest soils.
AB  - The present work was aimed at the isolation of additional new pure cultures of
      oxalate-degrading Streptomyces and its preliminary characterization for further
      work in the field of oxalate metabolism and taxonomic studies. Mesophilic,
      oxalate-degrading Streptomyces were enriched and isolated from plant rhizosphere
      and forest soil samples. Strains were examined for cultural, morphological (spore
      chain morphology, spore mass colour, diffusible and melanin pigment production),
      physiological (antibiosis, growth in the presence of inhibitory compounds,
      assimilation of organic acids and enzyme substrates) and chemotaxonomic
      characters (cellular lipid components and diagnostic cell-wall diamino acid). The
      taxonomic data obtained were analysed by using the simple matching (SSM) and
      Jaccard (Sj) coefficients, clustering was achieved using the UPGMA algorithm. All
      strains were able to utilize sodium-, potassium-, calcium- and ammonium-oxalate
      salts. Based on the results of numerical taxonomy, isolates were grouped into
      five cluster groups with a > or =70% S(SM) similarity level. Streptomyces rochei
      was the most common of the cluster groups, with a Willcox probability of P > 0.8.
      Streptomyces antibioticus, S. anulatus, S. fulvissimus, S. halstedii and S.
      violaceusniger are newly reported as oxalate-utilizing Streptomyces.

PMID- 15448923
TI  - A relict trematosauroid (Amphibia: Temnospondyli) from the Middle Jurassic of the
      Junggar Basin (NW China).
AB  - A temnospondyl ilium from the uppermost Toutunhe Formation (Middle Jurassic,
      Callovian) of the southern Junggar Basin is described. Among the known
      temnospondyls it is very unusual in morphology because of its very long and
      slender shaft. It compares closely only to the ilium of one of the latest known
      trematosaurids from the Ladinian of southern Germany. The Toutunhe Formation has
      also yielded vertebrae and skull fragments of temnospondyls which belong to the
      brachyopid Gobiops from the Upper Jurassic of Mongolia. Brachyopoid ilia do not,
      however, display a morphology similar to that of the new specimen. It is
      therefore concluded that this specimen represents a second taxon of temnospondyl
      from the Toutunhe Formation, which probably represents the latest surviving
      trematosauroid. The Trematosauroidea, which was hitherto exclusively known from
      the Lower to early Upper Triassic, therefore joins the Brachyopoidea--and
      possibly the Capitosauroidea --as another group of temnospondyls which survived
      the end--Triassic mass extinction.

PMID- 15448924
TI  - [Surgical technique for callus distraction].

PMID- 15448925
TI  - [Statin therapy in patients with acute coronary syndrome. "Prove-it" study].

PMID- 15448927
TI  - [Cutaneous alternariosis. Clinical diagnosis and therapeutic options].
AB  - Localized skin infections caused by the pigmented fungi of the genus Alternaria
      are being increasingly observed. In the past, primarily patients receiving long
      term glucocorticoid therapy were likely to have this mycosis, which is commonly
      traumatic, but now it is frequently encountered in organ transplantation
      patients. Possible therapeutic options and differential diagnosis are discussed
      by means of two case reports--a female renal transplant patient infected by A.
      alternata and a patient with iatrogenic Cushing syndrome infected by A.
      infectoria. Histopathological differentiation from other fungal infections may be
      difficult but is of therapeutic and prognostic significance. Finding short hyphae
      in tissue sections is an important clue. Since A. infectoria shows little
      conidial growth in culture, rDNA ITS sequencing offers another diagnostic
      possibility. Therapy has not yet been standardized. Along with surgical
      intervention, systemic itraconazole is the usual choice.

PMID- 15448926
TI  - [Trends and complications in the management of peritonsillar abscess with
      emphasis on children].
AB  - BACKGROUND: Peritonsillar abscess (PTA) is the most common deep neck space
      infection treated by otolaryngologists affecting predominantly young adults.
      Children present a challenge owing to the difficulty in obtaining an exact
      history and adequate physical examination. Particularly for the pediatric age
      group controversy surrounds the question of optimal treatment. This study was
      undertaken to evaluate bleeding complications following immediate tonsillectomy
      (TAC) in a pediatric population (<16 years) of age and to compare our management
      protocol with the current status in the literature. MATERIAL AND METHODS: The
      data of 218 children who had undergone TAC between January 1988 and January 2003
      in our clinic were enrolled in a retrospective study. The youngest patient was 18
      months, the oldest 15.9 years of age (mean: 14.53; median: 14; STD: 12.11 years).
      95 patients were male (43.6%), 123 female (56.4%). Various treatment protocols of
      the current literature are addressed. RESULTS: Postoperative hemorrhage (all from
      the opposite side) requiring surgical treatment under general anesthesia occurred
      in 4 children (1.8%). Repeated hemorrhage did not occur, blood transfusions were
      not required, there was no case with lethal outcome. Several reports indicate
      that needle aspiration (NP) or incision and drainage (ID) may suffice for the
      majority of cases but do not distinguish between different treatments for
      children and adults. More recently, conscious sedation has become a great support
      for pediatric treatment protocols. CONCLUSIONS: The initial success rates of NP
      or ID are both very high (>90%) and the overall recurrence rate is low,
      particularly in children. Only for selected subgroups, patients may profit from
      TAC, which was clearly not associated with an increased risk of bleeding in our
      pediatric population.

PMID- 15448928
TI  - [Painless cutaneous nodes in a 61-year old male stem cell transplantation
      patient].

PMID- 15448929
TI  - [Inpatient treatment costs of skin diseases. Diagnosis-based cost calculation in
      a university dermatology clinic].
AB  - BACKGROUND AND OBJECTIVE: With the advent of the DRG system, German hospitals are
      being forced to improve cost transparency and to uncover inefficient structures.
      METHODS: Diagnosis-based costs were calculated in the Department of Dermatology
      in the University Hospital of Freiburg for ten samples, each containing 20 cases.
      By using in-patient files, cost and productivity information for the fiscal year
      2000 was attributed to each single case in a bottom-up-approach. The resulting
      total costs per case were contrasted to their remuneration under the DRG system.
      RESULTS: Average case costs were determined between EUR 1,339.83 and EUR
      5,714.73. With 19.3% to 28.4% of total costs, nursing costs were the biggest
      single cost factor. Prolonging the length of stay incurred average extra costs of
      EUR 144.26 to EUR 199.98 per case and day. The correlation of case costs and
      their corresponding DRG cost weights was modest with r=0,48. There was
      considerable cost variance within individual DRGs. CONCLUSIONS: The diagnosis
      related cost calculation reveals striking cost differences relating to specific
      diagnoses. This method is more suitable for cost calculations in the hospital
      than more general approaches.

PMID- 15448930
TI  - [Current syphilis therapies and serological control. Commentary on the article by
      M. Hartmann in Hautarzt, Volume 2 (2004)].
AB  - Penicillin is currently the drug of choice for therapy of syphilis. Clemizole and
      procaine penicillin are no longer available. For this reason only benzathine
      penicillin and infusion therapy with benzyl penicillin are possible. Treatment
      with doxycyline or ceftriaxone is also conceivable. Suitable serological methods
      are necessary to control the safety of the therapy.

PMID- 15448931
TI  - [Hartmann's procedure indication in colorectal carcinoma].
AB  - Based on data obtained in a prospective, multicenter trial investigating the
      surgical treatment of colorectal carcinomas, the aim of this study was to
      investigate the value and relevance of Hartmann's procedure compared with
      alternative surgical approaches in elective interventions and emergency
      situations in carcinoma of the rectum (n=10,355) and the left hemicolon
      (n=8,825). Only in 3.4% (n=353) of patients with rectal carcinoma was the
      Hartmann's procedure executed with curative intention, indicating that this
      approach is recommendable only in (1) rare emergency situations (1.66%, n=172),
      (2) selected cases with elective intervention such as high-risk patients or
      subjects with poor prognosis, and (3) individuals with rectal carcinoma of the
      lower third who require deep resection (2+3, 1.75%, n=181). However, Hartmann's
      procedure resulted in the lowest mortality (7.5%) of the various procedures
      aiming for radical resection in the case of luminal obstruction or perforation at
      the left hemicolon. With palliative intention, 4.3% of patients with rectal
      carcinoma (n=449) received primary colostomies. At the left hemicolon, palliative
      segmental colon resection with primary anastomosis maintaining intestinal passage
      showed the lowest mortality (6.1%) and perioperative morbidity (33.9%) under
      elective circumstances, whereas Hartmann's procedure was preferred in emergency
      situations.

PMID- 15448932
TI  - [Relevance of surgical outpatient clinics in academic university centers to
      health care in Germany].
AB  - During the observation period between 2001 and 2003, all outpatient surgical
      therapy, including degrees of urgency, surgical care volume, regional provenance
      of patients, diagnoses, and referral channels were prospectively analysed at the
      Surgical Department of the University of Heidelberg, Germany. The data gathered
      do not merely describe the volume and characteristics of care encountered at this
      academic surgical institution but also provide further insight into the
      variability of resource utilisation and associated patient flow. Additionally, a
      retrospective evaluation using structured interviews and questionnaires was
      performed to differentiate and quantify patient care, teaching, and research
      activities. This study illustrates the high relevance of academic outpatient
      institutions to regional provision of general surgical care in Germany. There is
      a clear dominance of medical support functions, while research and teaching
      activities are of only minor relevance and realised particularly in subspecialty
      clinics. These data should give important stimuli for the future planning of
      health care in Germany. Outpatient clinics for general surgery appear to be an
      excellent basis for regional models of integrated health care delivery in the
      future.

PMID- 15448933
TI  - [Computer-assisted surgery for pelvic injuries].
AB  - For pelvic fractures, pre- and postoperative imaging includes spiral computed
      tomography, providing high resolution and accuracy. In conventional pelvic
      operations, these image data cannot be used directly. Intraoperative imaging is
      limited with fluoroscopy and visualization by the approaches. One solution in
      terms of precision and reduction of radiation exposure could be computer-assisted
      surgery (CAS). This method can be divided into navigation, which requires active
      registration, CT based navigation and registration-free fluoroscopy-based or Iso
      C-3D-based navigation. Applications for CAS in the pelvis include sacroiliac
      screw osteosynthesis in pelvic ring fractures, navigated periacetabular screw
      fixation, and correction operations for malhealed pelvic ring fractures.
      Nowadays, CAS is still costly and frequently requires additional staff. However,
      it helps to reduce complications caused by implant placement. With the
      introduction of new health care requirements in Germany, this may be an economic
      argument as well. Current developments focusing on accurate navigated reduction
      will provide new indications for CAS, further decrease complication rates, and
      help to reduce the invasiveness of pelvis operations.

PMID- 15448935
TI  - [Intraoperative imaging with the ISO C(3D)].
AB  - Computed tomography (CT) scanning is the gold standard for displaying and
      visualizing complex anatomic structures such as the calcaneus, pelvis, and spine,
      etc. In orthopedic surgery CT scanning is unfortunately not available in the OR
      where it would be highly effective if scans could be done prior to wound closure.
      The reasons are high costs, need for constructional changes in the OR, and
      additional staff (radiologic technologist), etc. For the first time the ISO C(3D)
      enables the surgeon to generate multiplanar reconstruction (MPR) pictures during
      surgery within an acceptable time frame at a reasonable price with a familiar
      instrument (a modified C-arm). Since February 2001 we have been able to use the
      ISO C(3D) in our hospital and meanwhile we have scanned 442 surgical sites
      including the calcaneus, cervical spine, and acetabulum, etc. The intraoperative
      scans revealed fracture gaps and steps, unsatisfactory fragment alignment, or
      incorrectly positioned implants, leading to an overall revision rate of 7.3%The
      ISO C(3D) is a first step towards a new future for bone visualization. The next
      steps will bring an increase in scan area and resolution, and the high-contrast
      pictures will be replaced by ones very similar to modern CT slices showing
      certain soft tissue structures.

PMID- 15448934
TI  - [Leakage after biliary and pancreatic surgery].
AB  - The frequency of anastomotic leaks after pancreatic resection is still
      significant. The majority of such leaks will heal without major clinical
      symptoms. In one fifth of patients, however, the sequelae of pancreatic leakage
      are serious and sometimes life-threatening. Management of such leaks ranges from
      local drainage to operative revision and completion pancreatectomy. The frequency
      of anastomotic leakage depends on a series of patient- and organ-specific risk
      factors. Surgical experience also plays a major role. Whether the prophylactic
      application of octreotide is able to reduce the frequency of pancreatic leaks is
      still a matter of debate. Leaks from direct bile duct sutures or biliodigestive
      anastomoses are rather seldom. Their clinical importance is limited. In case of a
      leak after direct bile duct anastomosis, endoscopic insertion of a stent seems to
      be the therapy of choice. Leaks from biliodigestive anastomoses which are
      diagnosed during the first 3 postoperative days should be treated by immediate
      operative revision. Late biliary leaks can be treated by local drainage. The
      results of bile duct surgery, too, are clearly dependent on the experience of the
      operating surgeon.

PMID- 15448936
TI  - ["Above too please"! Artificial respiration during cardiopulmonary
      resuscitation].

PMID- 15448937
TI  - [Propofol infusion syndrome].
AB  - Propofol infusion syndrome has not only been observed in patients undergoing long
      term sedation with propofol, but also during propofol anesthesia lasting 5 h. It
      has been assumed that the pathophysiologic cause is propofol's impairment of
      oxidation of fatty acid chains and inhibition of oxidative phosphorylation in the
      mitochondria, leading to lactate acidosis and muscular necrosis. It has been
      postulated that propofol might act as a trigger substrate in the presence of
      priming factors. Severe diseases in which the patient has been exposed to high
      catecholamine and cortisol levels have been identified as trigger substrates.
      Once the development of propofol infusion syndrome is suspected, propofol
      infusion has to be stopped immediately and specific therapeutic measures
      initiated, including cardiocirculatory stabilization and correction of metabolic
      acidosis. To increase elimination of propofol and its potential toxic
      metabolites, hemodialysis or hemofiltration are recommended. Due to its possible
      fatal side effects, the use of propofol for long-term sedation in critically ill
      patients should be reconsidered. In cases of unexplained lactate acidosis
      occurring during continuous propofol infusion, propofol infusion syndrome must be
      taken into consideration.

PMID- 15448938
TI  - [Laser-resistance of a new jet ventilation catheter (LaserJet) under simulated
      clinical conditions].
AB  - BACKGROUND: Laser surgery within the airway is often performed with the patient
      under general anaesthesia and with infraglottic jet ventilation via a specially
      designed catheter which should not be inflammable. We investigated the laser
      resistance of a recently introduced jet ventilation catheter (LaserJet) made of
      polytetrafluoroethylene. METHODS: For the simulation of gas accumulation in the
      hypopharynx a cylindric steel chamber with an open and a closed end was used to
      simulate the operative setting according to the European standard ISO-11990. In a
      series of 12 tests the disposable laser jet catheter was attached to the proximal
      end of the oxygen supply tubing, and the distal end was introduced 10 cm into the
      steel chamber. The catheter was repeatedly exposed to the beam of a CO(2)-laser
      device with energies varying from 2-15 W and with an impact angle of 75 degrees.
      The changes in the catheter were assessed with and without an oxygen flow of 6
      l/min. Time of exposure varied from 1 to 10 s. Size and nature of the changes in
      the catheter were documented. RESULTS: We found damage to the catheter that
      occurred in the following order: simple (front wall) and double perforation
      (front and back wall), smoke emission as evidence for pyrolysis, discolouration,
      deformation and rupture. The extent of damage to the catheter shaft under direct
      laser beam exposition was dependent on the laser intensity. When there was no
      oxygen flow, a beam of 2 W needed 40 s to perforate the catheter shaft, while
      with an oxygen flow of 6 l/min, a laser intensity of 4 W needed 20 s to cause
      perforation. Rupture of the catheter occurred in less than 10 s with a laser
      intensity of 8 W or more. CONCLUSIONS: We could demonstrate that the LaserJet
      catheter is not inflammable and also does not sustain fire. However, it is not
      laser-resistant as to maintaining its texture and shape while under direct
      exposure to a continuous laser beam, as applied under clinical conditions.
      Polytetrafluoroethylene deforms and melts at temperatures above 327 degrees C
      which is usually exceeded by the CO(2)-laser.

PMID- 15448939
TI  - Degradation of 4-nitrophenol by the lignin-degrading basidiomycete Phanerochaete
      chrysosporium.
AB  - The fungal metabolism of 4-nitrophenol (4-NP) was investigated using the lignin
      degrading basidiomycete, Phanerochaete chrysosporium. Despite its phenolic
      feature, 4-NP was not oxidized by extracellular ligninolytic peroxidases.
      However, 4-NP was converted to 1,2-dimethoxy-4-nitrobenzene via intermediate
      formation of 4-nitroanisole by the fungus only under ligninolytic conditions. The
      metabolism proceeded via hydroxylation of the aromatic ring and methylation of
      phenolic hydroxyl groups. Although the involvement of nitroreductase in the
      metabolism of 2,4-dinitrotoluene by many aerobic and anaerobic microorganisms
      including P. chrysosporium has been reported, no formation of 4-aminophenol was
      observed during 4-NP metabolism. The formation of 1,2-dimethoxy-4-nitrobenzene
      was effectively inhibited by exogenously added piperonyl butoxide, a cytochrome
      P450 inhibitor, suggesting that cytochrome P450 is involved in the hydroxylation
      reaction. Thus, P. chrysosporium seems to utilize hydroxylation and methylation
      reactions to produce a more susceptible structure for an oxidative metabolic
      system.

PMID- 15448940
TI  - Analysis of acyl CoA ester intermediates of the mevalonate pathway in
      Saccharomyces cerevisiae.
AB  - The mevalonate pathway plays an important role in providing the cell with a
      number of essential precursors for the synthesis of biomass constituents. With
      respect to their chemical structure, the metabolites of this pathway can be
      divided into two groups: acyl esters [acetoacetyl CoA, acetyl CoA,
      hydroxymethylglutaryl (HMG) CoA] and phosphorylated metabolites (isopentenyl
      pyrophosphate, dimethylallyl pyrophosphate, geranyl pyrophosphate, farnesyl
      pyrophosphate). In this study, we developed a method for the precise analysis of
      the intracellular concentration of acetoacetyl CoA, acetyl CoA and HMG CoA; and
      we used this method for quantification of these metabolites in Saccharomyces
      cerevisiae, both during batch growth on glucose and on galactose and in glucose
      limited chemostat cultures operated at three different dilution rates. The level
      of the metabolites changed depending on the growth phase/specific growth rate and
      the carbon source, in a way which indicated that the synthesis of acetoacetyl CoA
      and HMG CoA is subject to glucose repression. In the glucose batch, acetyl CoA
      accumulated during the growth on glucose and, just after glucose depletion, HMG
      CoA and acetoacetyl CoA started to accumulate during the growth on ethanol. In
      the galactose batch, HMG CoA accumulated during the growth on galactose and a
      high level was maintained into the ethanol growth phase; and the levels of acetyl
      CoA and HMG CoA were more than two-fold higher in the galactose batch than in the
      glucose batch.

PMID- 15448941
TI  - Constitutive expression and alternative splicing of the exons encoding SCRs in
      Sp152, the sea urchin homologue of complement factor B. Implications on the
      evolution of the Bf/C2 gene family.
AB  - The purple sea urchin, Strongylocentrotus purpuratus, possesses a non-adaptive
      immune system including elements homologous to C3 and factor B (Bf) of the
      vertebrate complement system. SpBf is composed of motifs typical of the Bf/C2
      protein family. Expression of Sp152 (encodes SpBf) was identified in the
      phagocyte type of coelomocyte in addition to gut, pharynx and esophagus, which
      may have been due to the presence of these coelomocytes in and on all tissues of
      the animal. Sp152 expression in coelomocytes was constitutive and non-inducible
      based on comparisons between pre- and post-injection with lipopolysaccharide or
      sterile seawater. The pattern of five short consensus repeats (SCRs) in SpBf has
      been considered ancestral compared to other deuterostome Bf/C2 proteins that
      contain either three or four SCRs. Three alternatively spliced messages were
      identified for Sp152 and designated Sp152Delta1, Sp152Delta4, and
      Sp152Delta1+Delta4, based on which of the five SCRs were deleted. Sp152Delta4 had
      an in-frame deletion of SCR4, which would encode a putative SpBfDelta4 protein
      with four SCRs rather than five. On the other hand, both Sp152Delta1 and
      Sp152Delta1+Delta4 had a frame-shift that introduced a stop codon six amino acids
      downstream of the splice site for SCR1, and would encode putative proteins
      composed only of the leader. Comparisons between the full-length SpBf and its
      several splice variants with other Bf/C2 proteins suggested that the early
      evolution of this gene family may have involved a combination of gene
      duplications and deletions of exons encoding SCRs.

PMID- 15448942
TI  - The complexity of expressed kappa light chains in egg-laying mammals.
AB  - Complementary DNAs encoding immunoglobulin light chains were isolated from two
      monotreme species, Ornithorhynchus anatinus (duckbill platypus) and Tachyglossus
      aculeatus (echidna). The sequences of both the variable and constant regions of
      these clones had greater similarity to IGK than to other light chain classes and
      phylogenetic analyses place them squarely within the mammalian IGK group,
      establishing them as monotreme IGK homologues. The constant region sequences of
      all clones were essentially identical within each species and, along with
      Southern blot results, the data are consistent with a single IGKC in each
      species. The expressed IGKV repertoires from both platypus and echidna were
      randomly sampled and there appear to be at least four platypus and at least nine
      echidna IGKV subgroups. The IGKV subgroups are highly divergent within species,
      in some cases sharing as little as 57% nucleotide identity. Two of the IGKV
      subgroups are present in both species, so there is some degree of overlap in the
      germline repertoires of these two monotremes. Overall the complexity seen in
      platypus and echidna IGK light chains is comparable with that of other mammals
      considered to have high levels of germline diversity and is in contrast to what
      has been found so far for monotreme IGL.

PMID- 15448943
TI  - Pigmented villonodular synovitis: MR imaging in pediatric patients.
AB  - OBJECTIVES: To describe the usefulness of gradient-echo imaging and contrast
      enhanced MR imaging in diagnosing and assessing the extent of pigmented
      villonodular synovitis (PVNS) in pediatric patients. PATIENTS AND METHODS:
      Retrospective analysis of five pediatric patients (median age 14 years) with PVNS
      of the knee examined with a 1.5-T unit. Signal characteristics were obtained
      comparing T1- and proton-density (PD)-weighted imaging with gradient-echo imaging
      and enhanced imaging. The extent of the disease was assessed using the
      arthroscopic approach. Signal intensity ratios were statistically analyzed.
      RESULTS: Compared to PD- and T1-weighted imaging sequences, gradient-echo imaging
      provides superior depiction of the extent of the disease due to signal decay (T2*
      effect) of hemosiderin-laden thickened synovium and masses. Inflamed synovium
      with low hemosiderin deposition was identified on enhanced imaging. Beside the
      suprapatellar bursa and Hoffa's fat pad, the area posterior to the cruciate
      ligaments is commonly involved. No bony abnormalities were present. CONCLUSION:
      Gradient-echo imaging together with enhanced imaging is useful in diagnosing and
      assessing the extent of PVNS in pediatric patients. A low signal mass behind the
      cruciate ligaments may represent an important diagnostic feature. Bony
      abnormalities were always absent.

PMID- 15448944
TI  - Coral as a substitute for bone grafts in delayed sternal closure in neonates.

PMID- 15448945
TI  - Imaging of traumatic dislocation of the hip in childhood.
AB  - BACKGROUND: Traumatic hip dislocation in childhood is a rare consequence of
      violent trauma. After reduction, outcome is usually favourable although
      epiphyseal necrosis can occur. Reduction must be carried out as soon as possible
      and is achieved easily, although if the labrum is involved, surgery may be
      required to achieve complete reduction. OBJECTIVE: To analyze a retrospective
      series of traumatic hip dislocations in children, describing the therapeutic and
      imaging strategy. MATERIALS AND METHODS: A total of 42 patients were studied.
      Their mean age was 10 years 3 months. All relevant radiographic, CT, MRI and
      radionuclide bone scan examinations were reviewed. Special attention was paid to
      associated lesions. RESULTS: In 22 patients the dislocation was caused by low
      energy trauma. Road traffic accidents accounted for 17 dislocations. An
      acetabular fracture was present in six patients and the femoral head was
      fractured in three. Reduction was easily achieved in 31 patients. In 11 patients
      the postreduction radiograph and CT showed joint space asymmetry secondary to
      labral entrapment. Only two patients developed epiphyseal necrosis. CONCLUSIONS:
      It has been difficult to define and evaluate accurate principles for a medical
      imaging strategy in this group of patients. Analysis of plain radiographs is
      essential before and after reduction of the joint, and it is important to perform
      postreduction CT in every patient whose joint space remains widened. A
      radionuclide bone scan should be performed between the second and third weeks
      after injury to assess epiphyseal vascularity. With the use of specific
      sequences, MRI may be an alternative modality to assess epiphyseal vitality.

PMID- 15448946
TI  - Ticks and tick paralysis: imaging findings on cranial MR.
AB  - Tick paralysis is an acute, progressive, and potentially fatal muscle paralysis
      secondary to a toxin secreted by a pregnant tick during a bite. Although tick
      bites can occur anywhere on the body, ticks are frequently overlooked on the
      scalp because of overlying hair. Children with acute neurologic symptoms
      frequently undergo MR scanning that may incidentally reveal the offending tick.
      Timely identification and removal of the tick leads to rapid recovery from tick
      paralysis. We report the MRI findings at 1.5 T of tick paralysis with an attached
      tick.

PMID- 15448947
TI  - Gastric volvulus as a complication of liver transplant.
AB  - We report a patient who developed mesenteroaxial gastric volvulus after a liver
      transplantation. We hypothesize that this complication may have been related to
      the ligation of the hepatogastric ligament done to mobilize the liver during
      hepatectomy.

PMID- 15448948
TI  - Peliosis hepatis causing inferior vena cava compression in a 3-year-old child.
AB  - Peliosis hepatis is a rare benign condition characterized by oval or irregular,
      multiple blood-filled spaces within the liver parenchyma. It is most commonly
      seen in adults and may be idiopathic, but has various associations including
      malignancy, infection and drugs. The imaging findings are often non-specific and
      the condition may be mistaken for multiple abscesses, metastases or vascular
      malformations. Peliosis hepatis is an especially rare condition in children and
      to our knowledge only six cases have been described in the literature. Our case
      describes and illustrates peliosis in a 3-year-old girl and is the first
      described in any age group to cause complete IVC obstruction. The patient
      subsequently made a full recovery.

PMID- 15448949
TI  - Diagnosis of vesicoureteric reflux with low-dose contrast-enhanced harmonic
      ultrasound imaging.
AB  - BACKGROUND: Harmonic US imaging has been shown to be better than conventional US
      for the detection and visualisation of microbubbles in contrast-enhanced voiding
      urosonography (VUS). OBJECTIVE: To determine the diagnostic efficacy of VUS using
      a reduced dose of the US contrast medium in comparison to voiding
      cystourethrography (VCUG). MATERIALS AND METHODS: Fifty-five children (17 boys,
      38 girls; mean age 4 years) were recruited. All patients underwent VUS by
      harmonic imaging followed by VCUG. The dose of the US contrast medium (Levovist)
      administered intravesically was half of the recommended dose i.e. 5% of the
      bladder filling volume. RESULTS: A total of 114 kidney-ureter (K-U) units were
      available for evaluation. Vesicoureteric reflux (VUR) was detected in 29 K-U
      units by one or both examination modalities. There was a 91.2% concordance rate
      between VUS and VCUG. VUR in seven and three K-U units were detected only by VUS
      and VCUG, respectively. Taking VCUG as the reference method, VUS had the
      following diagnostic results: 86.4% sensitivity, 92.4% specificity, positive and
      negative predictive values of 73.1 and 96.6%, respectively. CONCLUSIONS: Even
      when the dose of US contrast medium is halved, the diagnostic efficacy of
      harmonic VUS is comparable to VCUG. Consequently, we recommend an US contrast
      medium dose of 5% of the bladder filling volume for the diagnosis of VUR using
      contrast-enhanced harmonic VUS.

PMID- 15448950
TI  - CT findings of bilateral congenital absence of the long process of the incus.
AB  - Bilateral conductive deafness due to congenital absence of the long process of
      the incus (CALPI) is rare. The authors present the case of a patient with
      bilateral CALPI. To the best of our knowledge, this is the first reported case
      preoperatively diagnosed as bilateral CALPI by computed tomography. Multislice
      computed tomography is very useful for the diagnosis of minute abnormalities of
      the ossicles.

PMID- 15448951
TI  - Reversible encephalopathy syndrome: report of 12 cases with follow-up.
AB  - We report the clinical and neuroradiological features of reversible
      encephalopathy syndrome and follow-up results in 12 patients. This syndrome seems
      to be the result of an acute encephalopathy showing with brain edema mainly in
      the white matter (vasogenic edema). Diffusion-weighted magnetic resonance images
      are useful to distinguish this entity from acute ischemia. Early recognition and
      treatment often lead to complete neurological recovery. If unrecognized, the
      patient's condition can progress to central nervous system failure.

PMID- 15448952
TI  - Intracranial aneurysms: evaluation using CTA and MRA. Correlation with DSA and
      intraoperative findings.
AB  - Computed tomographic angiography (CTA) and magnetic resonance angiography (MSA)
      have been used recently for evaluation of intracranial aneurysms. If they are to
      replace conventional digital subtraction angiography (DSA), their sensitivity and
      specificity should be equal to the latter. In order to determine whether computed
      tomographic angiography and magnetic resonance angiography can provide the
      necessary information for presurgical evaluation we compared blindly the results
      of helical CT angiography and MR angiography with the results of digital
      subtraction angiography and the intraoperative findings. We evaluated 35 patients
      with the possible clinical diagnosis of intracranial aneurysm. Our data suggest
      that both CTA and MRA can provide valuable preoperative information concerning
      the location, the characteristics and the relationships of most intracranial
      aneurysms. Both original and reconstructed images should be evaluated together
      for higher accuracy. In addition helical CT, being a fast, inexpensive and
      noninvasive method, can be used as a reliable alternative to DSA in emergency
      situations demanding immediate operation.

PMID- 15448953
TI  - Diagnosis of spinal dural arteriovenous fistula with multidetector row computed
      tomography: a case report.
AB  - Spinal dural arteriovenous fistulas are a rare cause of myelopathy. Nonspecific
      symptoms may delay the diagnosis. Magnetic resonance imaging and spinal
      angiography are routinely used to establish the diagnosis. In our case
      abnormalities on magnetic resonance imaging only suggested spinal dural
      arteriovenous fistulas. Multidetector row computed tomography (MRCT) led to the
      diagnosis which was confirmed by angiography.

PMID- 15448954
TI  - Glucocorticoid treatment of brain tumor patients: changes of apparent diffusion
      coefficient values measured by MR diffusion imaging.
AB  - Glucocorticoids (GCC) generally are administered to patients with brain tumors to
      relieve neurological symptoms by decreasing the water content in a peritumoral
      zone of edema. We hypothesized that diffusion imaging and apparent diffusion
      coefficient (ADC) values could detect subtle changes of water content in brain
      tumors and in peritumoral edema after GCC therapy. The study consisted of 13
      patients with intra-axial brain tumor, and ADC was measured in the tumor, within
      peritumoral edema, and in normal white matter remote from the tumor before and
      after GCC therapy. ADC also was measured in normal white matter in four control
      patients with no intracranial disease who were treated with GCC for other
      indications. Conventional MR images showed no visually evident interval change in
      tumor size or the extent of peritumoral edema in any subject after GCC therapy,
      which nonetheless resulted in a decrease in mean ADC of 7.0% in tumors (P <
      0.05), 1.8% in peritumoral edema (P > 0.05, not significant) and 5.8% in normal
      white matter (P < 0.05). In patients with no intracranial disease, GCC therapy
      decreased mean ADC in white matter by 5.4% (P < 0.05). ADC measurement can
      demonstrate subtle changes in the brain after GCC therapy that cannot be observed
      by conventional MR imaging. Measurement of ADC proved to be a sensitive means of
      assessing the effect of GCC therapy, even in the absence of visually discernible
      changes in conventional MR images.

PMID- 15448955
TI  - Pharmacokinetic differences between the enantiomers of lansoprazole and its
      metabolite, 5-hydroxylansoprazole, in relation to CYP2C19 genotypes.
AB  - OBJECTIVE: The purpose of this study was to elucidate the pharmacokinetics of
      each enantiomer of lansoprazole and 5-hydroxylansoprazole in three different
      CYP2C19 genotype groups of Japanese subjects. METHODS: Healthy subjects ( n=18),
      of whom 6 were homozygous extensive metabolizers (homEMs), 6 were heterozygous
      extensive metabolizers (hetEMs) and 6 were poor metabolizers (PMs), participated
      in the study. After a single oral dose of 60 mg of racemic lansoprazole, the
      plasma concentrations of the lansoprazole enantiomers, 5-hydroxylansoprazole
      enantiomers and lansoprazole sulfone were measured for 24 h post-dose. RESULTS:
      The plasma concentrations of ( R)-lansoprazole were remarkably higher in all
      three CYP2C19 genotype groups than those of the corresponding ( S)-enantiomer.
      The mean maximum plasma concentration ( C(max)) of ( S)-lansoprazole differed
      significantly among the three groups, whereas there was no difference for the (
      R)-enantiomer. The relative area under the plasma concentration (AUC) ratios of (
      R)- and ( S)-lansoprazole in the homEMs, hetEMs, and PMs were 1:1.5:4.0 and
      1:1.8:7.4, respectively. Yet, the relative AUC ratios of 5-hydroxylansoprazole to
      lansoprazole for the ( R)- and ( S)-enantiomers in the homEMs, hetEMs, and PMs
      were almost the same (1:0.73:0.12 and 1:0.77:0.13, respectively). However, the
      AUC ratios of the ( S)-enantiomer were 13-fold greater for the three CYP2C19
      genotypes than those of the corresponding ( R)-enantiomer. CONCLUSIONS: The
      magnitude of the contribution of CYP2C19 to the 5-hydroxylation of ( S)
      lansoprazole was greater than that of the ( R)-enantiomer. The R/S ratios for the
      AUC of lansoprazole for the homEMs, hetEMs and PMs were 12.7, 8.5 and 5.8,
      respectively, suggesting a significant effect of CYP2C19 polymorphisms on the
      stereoselective disposition of lansoprazole.

PMID- 15448956
TI  - Are we going to increase the use of antidepressants up to that of
      benzodiazepines?
AB  - OBJECTIVE: The present study compared recent trends in benzodiazepine and
      antidepressant consumption in Italy and projected their global sales in the
      future. We investigated whether the increasing use of antidepressants is
      associated with a progressive reduction in benzodiazepine use. METHODS: Data
      concerning actual quantities of benzodiazepines and antidepressants dispensed in
      Italy from 1995 to June 2003 were obtained from IMS Health. For each agent, the
      number of defined daily doses (DDDs) per 1000 inhabitants per day and the annual
      expenditure in Euros was calculated. RESULTS: During the 9-year period,
      benzodiazepine consumption remained substantially stable, accounting for 50
      DDDs/1000 per day in 2003. In the same period, antidepressant consumption
      dramatically rose, from 9 DDDs/1000 per day in 1995 to 26 DDDs/1000 per day in
      2003, an increase of nearly three times. While the use of tricyclic
      antidepressants declined by one-third and that of other older agents remained
      substantially stable, the use of selective serotonin-reuptake inhibitors and
      newer agents (venlafaxine, mirtazapine, reboxetine) increased by 623%. Global
      consumption of antidepressants was projected to increase still further, and, in
      2007, the total sales of antidepressants were projected to be similar to the
      total sales of benzodiazepines. The value of benzodiazepine sales increased from
      322 million to 565 million Euros, an increase of 43%; similarly, the value of
      antidepressant sales increased from 186 million to 569 million Euros, an increase
      of 67%. CONCLUSIONS: In Italy, the consumption of benzodiazepines was not
      affected by the increased prescribing of selective serotonin-reuptake inhibitors
      and newer antidepressants.

PMID- 15448957
TI  - A case control study to examine the pharmacological factors underlying
      ventricular septal defects in the North of England.
AB  - BACKGROUND: Amphetamine exposure is associated with congenital cardiac
      abnormalities in animals. We previously reported an association between
      recreational use of 2,4-methylenedioxymethamphetamine (ecstasy, MDMA) and
      ventricular septal defect in babies born to users. We have carried out a case
      control study to investigate risks in the occurrence of ventricular septal defect
      in a cohort of babies born in the North East of England. METHODS: Cases were
      identified from paediatric cardiology units in Newcastle upon Tyne and Leeds, and
      controls were recruited from the mothers of babies born in the same hospital as
      the index case. Research nurses carried out interviews using a structured
      questionnaire. RESULTS: A total of 296 case control pairs were studied. There was
      insufficient exposure to ecstasy to test the primary hypothesis. Increased risk
      of ventricular septal defect was found to be associated with consumption of cough
      and cold remedies [pre-conception OR 2.2, 95% CI 1.41, 3.51; pregnancy OR 5.1,
      95% CI 2.56, 11.27; exposure in either OR 2.83, 95% CI 1.85, 4.45; P<0.005] and
      in the case of non-steroidals for exposures in pregnancy (OR 4.2, 95% CI 1.54,
      14.26; P<0.005). CONCLUSIONS: These findings suggest that ventricular septal
      defect is associated with consuming the medications identified. They are also
      compatible with the hypothesis that sympathomimetics (pseudoephedrine,
      phenylephrine and phenylpropanolamine) present in cough mixtures cause the
      increased risk, and with our original hypothesis that sympathomimetics and
      amphetamines are potentially cardiotoxic in utero.

PMID- 15448958
TI  - Strategies and determinants for selection of alternate foot placement during
      human locomotion: influence of spatial and temporal constraints.
AB  - During locomotion in a cluttered terrain, certain terrain surfaces such as an icy
      one are not appropriate for foot placement; an alternate choice is required. In a
      previous study we showed that the selection of foot placement is not random but
      systematic; the dominant choices made are not uniquely defined by the available
      or predicted sensory inputs. We argued that selection is guided by specific rules
      and involves minimal displacement of the foot from its normal landing spot. The
      experimental protocol involved implicit spatial constraint by requiring
      individuals to step on the force plate that could trigger a lighted area to be
      avoided, thereby requiring individuals to respond within one step-cycle.
      Alternate foot placement was visually identified, but not measured. The purpose
      of this study was to directly measure foot placement, validate and/or refine the
      rules used to guide selection, and identify whether the alternate foot placement
      choices are influenced by spatial and temporal constraints on response selection.
      The area to be avoided was visible from the start and therefore individuals could
      plan and implement appropriate avoidance strategies without any temporal
      constraint. Spatial constraint introduced in this experiment included requirement
      both to step on a specific location and to avoid stepping on a specific location
      on the next step. The results provide support for the rules previously identified
      in guiding foot placement to an alternate location. Minimal displacement of the
      foot from its normal landing spot was validated as an important factor for
      selecting alternate foot placement. When several choices satisfied this factor,
      additional factors guide alternate foot placement. Modifications in the plane of
      progression are preferred while stepping wide is avoided. When no temporal
      constraints are imposed on the response selection, enhancing forward progression
      of the body becomes the dominant determinant followed by stability and lastly by
      energy costs associated with the modifications. A decision algorithm for
      selecting foot placement is proposed based on these findings. It is clear that
      while visual input plays a critical role in guiding foot placement, it is not
      entirely based on reactive control. This has implications for implementing
      visually guided adaptive locomotion in legged robots.

PMID- 15448959
TI  - Recovery of saccadic dysmetria following localized lesions in monkey superior
      colliculus.
AB  - Damage to the monkey superior colliculus (SC) produces deficits in the generation
      of saccadic eye movements. Recovery of the accuracy of saccades is rapid, but
      saccadic latency and peak velocity recover slowly or not at all. In the present
      experiments we revisited the issue of recovery of function following localized
      lesions of the SC using three methodological advances: implantation of wire
      recording electrodes into the SC for the duration of the experiment to ensure
      that we were recording from the same site on the SC map on successive days;
      quantification of changes in saccadic accuracy, latency, and velocity using a
      standard grid of target points in the visual field contralateral to the SC
      lesion; measurement of movement field size to quantitatively determine any
      changes following the lesion. We confirmed a decrease in saccadic accuracy
      following electrolytic lesions of the SC, and we found that this dysmetria
      recovered within about 4 days. Saccadic latency increased for saccades to the
      lesion area and this deficit persisted. Peak saccadic velocity decreased
      immediately after the lesion and decreased further during the 10 days to 2 weeks
      of the experiment. We found no indication of an expansion of the movement fields
      of neurons adjacent to the lesion area. This lack of reorganization suggests that
      movement field changes within the SC cannot mediate the recovery in accuracy of
      the saccade. The persistence of the latency and velocity deficits despite the
      recovery of amplitude deficits indicates that saccadic latency and peak velocity
      are dependent upon the SC whereas saccadic amplitude is not.

PMID- 15448960
TI  - Serotoninergic-mediated inhibition of substance P sensitive deep dorsal horn
      neurons: a combined electrophysiological and morphological study in vitro.
AB  - Dorsal horn neurons that express the neurokinin 1 receptor (NK-1R) play an
      important role in nociceptive processing. The targetting of NK-1R neurons by
      serotoninergic (5-hydroxytryptamine, 5-HT) axons would provide a straightforward
      means to exert an inhibitory analgesic effect at spinal level. This study used
      single cell electrophysiology to analyse and correlate the responses of rat deep
      DH neurons in vitro to both 5-HT and the NK-1R agonist [Sar9,Met(O2)11]-substance
      P (SP). Subsequently a combination of immunocytochemistry and confocal imaging
      was applied to biocytin-filled laminae III-VI neurons to reveal putative 5-HT
      innervation in this neuronal sample. A population of neurons was identified in
      which 5-HT (50 microM) significantly attenuated the dorsal root-evoked excitatory
      postsynaptic potential and [Sar9,Met(O2)11]-SP (2 microM) induced a direct
      tetrodotoxin-resistant depolarisation. Immunolabelling revealed that all of these
      neurons were inhibited by 5-HT, including those that were excited by
      [Sar9,Met(O2)11]-SP, were overlaid by a plexus of 5-HT immunoreactive fibres and
      in some instances, closely apposed putative contacts with somata and proximal
      dendrites identified although their incidence was low. Inhibition by 5-HT of deep
      DH neurons directly responsive to SP may account at least in part for monoamine
      induced modulation of nociceptive processing in the spinal cord.

PMID- 15448961
TI  - Validity of the speed-accuracy tradeoff for prehension movements.
AB  - Subjects (n=12) grasped mirror-viewed visual targets with thumb and index finger,
      while prescribed movement time differed between blocks of trials. The variability
      of both final grip aperture (i.e. distance between thumb and index finger) and of
      final wrist position increased with decreasing movement time, indicating the
      existence of a speed-accuracy tradeoff both in the grasp and in the transport
      component of prehension. This tradeoff was limited to relatively short movement
      times (<400 ms) for the grasp component, but it extended to longer movement times
      for the transport component, which supports the view that the two components are
      controlled by separate mechanisms.

PMID- 15448962
TI  - Corticospinal activation of internal oblique muscles has a strong ipsilateral
      component and can be lateralised in man.
AB  - Trunk muscles receive corticospinal innervation ipsilaterally and contralaterally
      and here we investigate the degree of ipsilateral innervation and any cortical
      asymmetry in pairs of trunk muscles and proximal and distal limb muscles.
      Transcranial magnetic stimulation (TMS) was applied to left and right motor
      cortices in turn and bilateral electromyographic (EMG) recordings were made from
      internal oblique (IO; lower abdominal), deltoid (D; shoulder) and first dorsal
      interosseus (1DI; hand) muscles during voluntary contraction in ten healthy
      subjects. We used a 7-cm figure-of-eight stimulating coil located 2 cm lateral
      and 2 cm anterior to the vertex over either cortex. Incidence of ipsilateral
      motor evoked potentials (MEPs) was 85% in IO, 40% in D and 35% in 1DI. Mean (+/-
      S.E.M.) ipsilateral MEP latencies were longer ( P<0.05; paired t-test) than
      contralateral MEP latencies (contralateral vs. ipsilateral; IO: 16.1+/-0.4 ms vs.
      19.0+/-0.5 ms; D: 9.7+/-0.3 ms vs. 15.1+/-1.9 ms; 1DI: 18.3+/-0.6 ms vs. 23.3+/
      1.4 ms), suggesting that ipsilateral MEPs were not a result of interhemispheric
      current spread. Where data were available, we calculated a ratio (ipsilateral MEP
      areas/contralateral MEP areas) for a given muscle (IO: n=16; D: n=8; 1DI: n=7
      ratios). Mean values for these ratios were 0.70+/-0.20 (IO), 0.14+/-0.05 (D) and
      0.08+/-0.02 (1DI), revealing stronger ipsilateral drive to IO. Comparisons of the
      sizes of these ratios revealed a bias towards one cortex or the other (four
      subjects right; three subjects left). The predominant cortex showed a mean ratio
      of 1.21+/-0.38 compared with 0.26+/-0.06 in the other cortex ( P<0.05). It
      appears that the corticospinal control of IO has a strong ipsilateral component
      relative to the limb muscles and also shows hemispheric asymmetry.

PMID- 15448963
TI  - Simultaneous determination of L-arginine and its mono- and dimethylated
      metabolites in human plasma by high-performance liquid chromatography-mass
      spectrometry.
AB  - A simple, fast, sensitive, and reproducible isocratic liquid chromatography-mass
      spectrometry (LC-MS) method coupled with an atmospheric pressure chemical
      ionization (APCI) interface for simultaneous separation and determination of L
      arginine (ARG) and its methylated metabolites, N-monomethyl- L-arginine (MMA),
      NG, NG-dimethylarginine (asymmetric dimethyl arginine, ADMA), and NG, N'G
      dimethylarginine (symmetric dimethyl arginine, SDMA), in human plasma is
      presented. Sample pretreatment is not required other than deproteinization with 5
      sulfosalicylic acid (5-SSA). Satisfactory chromatographic separation was achieved
      on a 2.0x150-mm Shimadzu VP-ODS column by using a mobile phase consisting of
      water/acetonitrile (90/10, v/v) containing 0.5% trifluoroacetic acid (TFA).
      Positive selective ion monitoring (SIM) mode was chosen for quantification of
      each analyte. The positively protonated molecular ions [M+H]+ of ARG, MMA, ADMA,
      and SDMA were monitored at m/z 175, 189, 203, and 203, respectively. L
      Homoarginine was used as the internal standard (IS) for the assay. The limits of
      quantification (LOQs) were found to be 1.0 micromol L(-1) for ARG, and 0.2
      micromol L(-1) for MMA, ADMA, and SDMA. The inter-assay precision and accuracy
      were in the range of 1.8-4.9% and -3.0-5.0%, respectively. The intra-assay
      precision and accuracy were in the order of 1.7-4.6 and -2.6-4.0%, respectively.
      The recoveries were between 90.0 and 106.6%. The levels of ARG, MMA, ADMA, and
      SDMA in human plasma were also determined using the developed method.

PMID- 15448964
TI  - Total ranking models by the genetic algorithm variable subset selection (GA-VSS)
      approach for environmental priority settings.
AB  - Total order ranking (TOR) strategies, which are mathematically based on
      elementary methods of discrete mathematics, seem to be attractive and simple
      tools for performing data analysis. Moreover order-ranking strategies seem to be
      a very useful tool not only to perform data exploration but also to develop order
      ranking models, a possible alternative to conventional quantitative structure
      activity relationship (QSAR) methods. In fact, when data material is
      characterised by uncertainties, order methods can be used as alternative to
      statistical methods such as multilinear regression (MLR), because they do not
      require specific functional relationships between the independent and dependent
      variables (responses). A ranking model is a relationship between a set of
      dependent attributes, experimentally investigated, and a set of independent
      attributes, i.e. model attributes, which are calculated attributes. As in
      regression and classification models, the variable selection model is one of the
      main steps in finding predictive models. In this work the genetic algorithm
      variable subset selection (GA-VSS) approach is proposed as the variable selection
      method for searching for the best ranking models within a wide set of variables.
      The models based on the selected subsets of variables are compared with the
      experimental ranking and evaluated by the Spearman's rank index. A case study
      application is presented on a TOR model developed for polychlorinated biphenyl
      (PCB) compounds, which have been analysed according to some of their
      physicochemical properties which play an important role in their environmental
      impact.

PMID- 15448965
TI  - Chromatographic analysis of sugars applied to the characterisation of monofloral
      honey.
AB  - The control of the floral quality of honey has become a priority issue as a
      result of the number of abuses observed and the relative ease of getting around
      existing control methods. We conducted chromatographic analyses of honey sugars
      to determine new criteria for authenticating an origin. The work involved
      creating databases by analysing a large number of authentic honeys from seven
      monofloral varieties, followed by statistical processing of the results by a
      principal components analysis. Differences in composition could thus be
      demonstrated, such as the presence of trisaccharides in fir honey, that provide
      an additional tool for authenticating unknown commercial honeys.

PMID- 15448966
TI  - Information theory for evaluating environmental classification systems.
AB  - Environmental pollution data are often ranked in rule-based classification
      systems. These environmental data are separated in predetermined classes of a
      classification system for a better and smarter characterization of the state of
      pollution. Often the measured values are transformed, e.g. in pseudocolor maps,
      and can then be presented in maps. For some environmental compartments different
      classification systems for evaluating environmental loadings are used. Because of
      the dissimilarity of the various classification systems direct visual comparison
      is difficult. However, by means of information theory an objective comparison of
      these various classification systems based on their information content enables a
      decision to be made about which system is the most informative for objective
      assessment of the state of pollution. By means of the new measure "multiple
      medium information content" (multiple entropy) objective and simultaneous
      comparison of all channels (in an environmental classification system:
      pollutants) of each classification system is now possible. Furthermore the
      development of the state of pollution over the whole investigation period can be
      detected by means of information theory. On the basis of the conditions of the
      established rule-based systems the use of information theory enables definition
      of new ranges of classes in order to reach the optimum of information during
      conversion into the environmental classification system.

PMID- 15448967
TI  - Glucose oxidase-magnetite nanoparticle bioconjugate for glucose sensing.
AB  - Immobilization of bioactive molecules on the surface of magnetic nanoparticles is
      of great interest, because the magnetic properties of these bioconjugates promise
      to greatly improve the delivery and recovery of biomolecules in biomedical
      applications. Here we present the preparation and functionalization of magnetite
      (Fe3O4) nanoparticles 20 nm in diameter and the successful covalent conjugation
      of the enzyme glucose oxidase to the amino-modified nanoparticle surface.
      Functionalization of the magnetic nanoparticle surface with amino groups greatly
      increased the amount and activity of the immobilized enzyme compared with
      immobilization procedures involving physical adsorption. The enzymatic activity
      of the glucose oxidase-coated magnetic nanoparticles was investigated by
      monitoring oxygen consumption during the enzymatic oxidation of glucose using a
      ruthenium phenanthroline fluorescent complex for oxygen sensing. The glucose
      oxidase-coated magnetite nanoparticles could function as nanometric glucose
      sensors in glucose solutions of concentrations up to 20 mmol L(-1).
      Immobilization of glucose oxidase on the nanoparticles also increased the
      stability of the enzyme. When stored at 4 degrees C the nanoparticle suspensions
      maintained their bioactivity for up to 3 months.

PMID- 15448968
TI  - Wavelet multiscale regression from the perspective of data fusion: new conceptual
      approaches.
AB  - Wavelet regression is a very promising technique for modern multivariate
      calibration and calibration transfer. Multiscale analysis of wavelet scales
      provides a connection between wavelet regression and data fusion. In this paper,
      current wavelet regression methods are reviewed from the novel perspective of
      data fusion. Illustrated by analysis of a public domain near-infrared dataset,
      the advantages and drawbacks of these methods are examined. For wavelet
      regression, the non-uniformity of the wavelet components, the multiscale nature
      of the signal, and the prevention of information leakage are crucial issues that
      will be addressed.

PMID- 15448969
TI  - Using chemometrics for navigating in the large data sets of genomics, proteomics,
      and metabonomics (gpm).
AB  - This article describes the applicability of multivariate projection techniques,
      such as principal-component analysis (PCA) and partial least-squares (PLS)
      projections to latent structures, to the large-volume high-density data
      structures obtained within genomics, proteomics, and metabonomics. PCA and PLS,
      and their extensions, derive their usefulness from their ability to analyze data
      with many, noisy, collinear, and even incomplete variables in both X and Y. Three
      examples are used as illustrations: the first example is a genomics data set and
      involves modeling of microarray data of cell cycle-regulated genes in the
      microorganism Saccharomyces cerevisiae. The second example contains NMR
      metabonomics data, measured on urine samples of male rats treated with either of
      the drugs chloroquine or amiodarone. The third and last data set describes
      sequence-function classification studies in a set of G-protein-coupled receptors
      using hierarchical PCA.

PMID- 15448970
TI  - Determination of acidity constants of enolisable compounds by capillary
      electrophoresis.
AB  - Research on the structure-activity relationships of molecules with acidic carbon
      atoms led us to undertake a feasibility study on the determination of their
      acidity constants by capillary electrophoresis (CE). The studied molecules had
      diverse structures and were tetronic acid, acetylacetone, diethylmalonate,
      Meldrum's acid, 3-methylrhodanine, nitroacetic acid ethyl ester, pyrimidine-2,4,6
      trione, 3-oxo-3-phenylpropionic acid ethyl ester, 1-phenylbutan-1,3-dione, 5,5
      dimethylcyclohexan-1,3-dione and homophthalic anhydride. The p Ka range explored
      by CE was therefore very large (from 3 to 12) and p Ka values near 12 were
      evaluated by mathematical extrapolations. The analyses were carried out in CZE
      mode using a fused silica capillary grafted (or not) with hexadimethrine. Owing
      to the electrophoretic behaviour of these compounds according to the pH, their
      acidity constants could be evaluated and appeared in perfect agreement with the
      literature data obtained, a few decades ago, by means of potentiometry,
      spectrometry or conductimetry. The p Ka of homophthalic anhydride and 3
      methylrhodanine were evaluated for the first time.

PMID- 15448971
TI  - Use of near infrared spectroscopy in a study of binding media used in paintings.
AB  - The present study illustrates the use of near infrared spectroscopy in the
      conservation and restoration field. This application of the technique, widely
      used in other fields such as the agricultural and food industries, is very
      interesting due to two of its features: rapidity and non-destructiveness. In this
      study, three classification algorithms have been used to attempt to correlate the
      spectra of the samples under study--mixtures of two pigments (one organic and the
      other inorganic)--with binder recipes found in literature. Some of these recipes
      have very similar compositions, but they were distinguished into groups,
      depending on the painting technique associated with them.

PMID- 15448972
TI  - Government service: the third venue.

PMID- 15448974
TI  - Element content and element correlations in Chinese human liver.
AB  - The amounts of the 19 elements As, Br, Ca, Cd, Ce, Co, Cr, Cs, Fe, K, La, Mo, Na,
      Rb, Sb, Sc, Se, Sm, and Zn in 92 lyophilized autopsy human liver samples from
      normal subjects have been analyzed by instrumental neutron-activation analysis
      (INAA). For intercomparison and quality control ten samples were independently
      analyzed in two institutes, the Institute of High Energy Physics in China and the
      "Jozef Stefan" Institute in Slovenia. Most of the element contents determined by
      the two institutes were in quite good agreement, even though different
      experimental conditions were applied, indicating the reliability of the
      analytical results. Analysis of the chemical species of mercury present in the
      ten liver samples was also performed in Slovenia. Possible differences between
      the element content of male and female liver samples were studied by means of
      Student's t-test, but significant differences were found only for Ce, Co, Fe, La,
      Mo, and Zn. The results obtained were also compared with those reported from
      other areas of the world; no appreciable differences were observed. Correlation
      among the various elements in the human liver samples was studied using
      multivariate statistics. It was found that there was relatively close correlation
      between some elements, for example As-Fe, Ca-Fe, Cd-Co, Cd-Zn, Mo-Zn, Co-Se, Cs
      Rb, Br-Rb, Sc-Sm, La-Sm, La-Ce, etc.; these correlations could be rationally
      explained by the similarity of the electronic structures of the elements and/or
      their physiological functions in the human body.

PMID- 15448975
TI  - Attenuation of d-amphetamine-induced disruption of conditional discrimination
      performance by alpha-flupenthixol.
AB  - RATIONALE: Previous evidence suggests that manipulation of forebrain dopamine
      (DA) systems may impair the use of conditional information to inform goal
      directed performance, and this may be related to impairments in the ability to
      use task-setting cues in schizophrenia. OBJECTIVE: To investigate, using the
      indirect DA agonist d-amphetamine and the D1/D2 receptor antagonist alpha
      flupenthixol, the influence of DAergic manipulation on discrimination performance
      that requires the use of conditional information to inform goal-directed
      performance. METHODS: Both instrumental and Pavlovian conditional discriminations
      were employed in which rats learned to respond appropriately according to the
      presence of auditory conditional stimuli, and results from these experiments were
      contrasted with a control Pavlovian-instrumental transfer task. RESULTS:
      Experiment 1 showed a disruption of instrumental conditional discrimination
      performance by d-amphetamine at 1.5 mg/kg and attenuation of correct responding
      following 1.0 mg/kg. Disruption with both doses was observed in experiment 2
      using a conditional discrimination based on Pavlovian, conditioned responding.
      Results from a control Pavlovian-instrumental transfer task (experiment 3)
      revealed that d-amphetamine (0.5, 1.0 and 1.5 mg/kg) did not have any detrimental
      effect on subjects' basic sensory, motor or motivational processes. Experiment 4
      showed that d-amphetamine disruption of instrumental conditional discrimination
      was attenuated by pre-treatment with the D1/D2 receptor antagonist alpha
      flupenthixol. CONCLUSION: These results demonstrate that tasks dependent on
      conditional relationships are highly sensitive to manipulation of DAergic
      systems.

PMID- 15448976
TI  - Anticataleptic properties of alpha2 adrenergic antagonists in the crossed leg
      position and bar tests: differential mediation by 5-HT1A receptor activation.
AB  - RATIONALE: Recent studies suggest that alpha(2) adrenoceptor blockade may improve
      the antipsychotic-like effects of neuroleptics and attenuate dopamine D(2)
      receptor antagonist-induced catalepsy. However, several alpha(2) adrenergic
      antagonists also display serotonin 5-HT(1A) receptor agonist activity, which may
      contribute to anticataleptic actions. OBJECTIVES: In this study, we examined a
      series of alpha(2) adrenergic antagonists to determine the role of activity at
      serotonin 5-HT(1A) receptors in their anticataleptic effects. METHODS: Catalepsy
      in rats induced by the antipsychotic haloperidol (2.5 mg/kg, SC) was measured
      using the cross-legged position (CLP) and bar tests. The compounds examined in
      this study, in decreasing rank order of alpha(2) adrenergic versus 5-HT(1A)
      receptor selectivity, were atipamezole, methoxy-idazoxan (RX821002), efaroxan,
      idazoxan, and yohimbine. Antagonism studies were conducted using the selective 5
      HT(1A) receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2
      pyridinyl) cyclohexanecarboxamide dihydrochloride (WAY100635). RESULTS: Idazoxan,
      efaroxan, and yohimbine significantly attenuated the cataleptic effects of
      haloperidol (2.5 mg/kg, SC) in the CLP test and the actions of their highest
      doses were significantly blocked by pre-treatment with WAY100635 (0.63 mg/kg,
      SC). In contrast to the other compounds, methoxy-idazoxan was ineffective in the
      CLP test. Atipamezole exhibited anticataleptic effects in the bar and CLP tests
      which were not blocked by WAY100635. Similarly, the anticataleptic effects of
      methoxy-idazoxan and idazoxan in the bar test were not blocked by WAY100635.
      CONCLUSIONS: Serotonin 5-HT(1A) receptors play a prominent role in anticataleptic
      effects of certain alpha(2) adrenergic antagonists in the CLP test, whereas
      alpha(2)-adrenergic mechanisms are likely to be primarily responsible for the
      anticataleptic effects of these ligands in the bar test.

PMID- 15448977
TI  - A critical review of caffeine withdrawal: empirical validation of symptoms and
      signs, incidence, severity, and associated features.
AB  - RATIONALE: Although reports of caffeine withdrawal in the medical literature date
      back more than 170 years, the most rigorous experimental investigations of the
      phenomenon have been conducted only recently. OBJECTIVES: The purpose of this
      paper is to provide a comprehensive review and analysis of the literature
      regarding human caffeine withdrawal to empirically validate specific symptoms and
      signs, and to appraise important features of the syndrome. METHODS: A literature
      search identified 57 experimental and 9 survey studies on caffeine withdrawal
      that met inclusion criteria. The methodological features of each study were
      examined to assess the validity of the effects. RESULTS: Of 49 symptom categories
      identified, the following 10 fulfilled validity criteria: headache, fatigue,
      decreased energy/activeness, decreased alertness, drowsiness, decreased
      contentedness, depressed mood, difficulty concentrating, irritability, and
      foggy/not clearheaded. In addition, flu-like symptoms, nausea/vomiting, and
      muscle pain/stiffness were judged likely to represent valid symptom categories.
      In experimental studies, the incidence of headache was 50% and the incidence of
      clinically significant distress or functional impairment was 13%. Typically,
      onset of symptoms occurred 12-24 h after abstinence, with peak intensity at 20-51
      h, and for a duration of 2-9 days. In general, the incidence or severity of
      symptoms increased with increases in daily dose; abstinence from doses as low as
      100 mg/day produced symptoms. Research is reviewed indicating that expectancies
      are not a prime determinant of caffeine withdrawal and that avoidance of
      withdrawal symptoms plays a central role in habitual caffeine consumption.
      CONCLUSIONS: The caffeine-withdrawal syndrome has been well characterized and
      there is sufficient empirical evidence to warrant inclusion of caffeine
      withdrawal as a disorder in the DSM and revision of diagnostic criteria in the
      ICD.

PMID- 15448978
TI  - Differences in the effects of 5-HT(1A) receptor agonists on forced swimming
      behavior and brain 5-HT metabolism between low and high aggressive mice.
AB  - RATIONALE: Male wild house-mice genetically selected for long attack latency
      (LAL) and short attack latency (SAL) differ in structural and functional
      properties of postsynaptic serotonergic-1A (5-HT(1A)) receptors. These mouse
      lines also show divergent behavioral responses in the forced swimming test (FST,
      i.e., higher immobility by LAL versus SAL mice). OBJECTIVES: We investigated
      whether the line difference in 5-HT(1A) receptors is associated with a difference
      in brain 5-HT metabolism, and whether acute administration of a 5-HT(1A) receptor
      agonist could differentially affect the behavioral responses of LAL and SAL mice.
      METHODS: 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) levels were measured in
      homogenates of several brain regions using high-performance liquid
      chromatography. The behavioral effect of the full 5-HT(1A) receptor agonist, 8-OH
      DPAT, and of the somatodendritic 5-HT(1A) autoreceptor agonist, S-15535, was
      examined in the FST. The effect of 8-OH-DPAT on forced swimming-induced 5-HT
      metabolism in brain homogenates was determined. RESULTS: In most brain regions, 5
      HT and 5-HIAA levels and 5-HT turnover were not significantly different between
      LAL and SAL mice. 8-OH-DPAT abolished the behavioral line difference in the FST
      by reducing immobility in LAL mice and reducing climbing in SAL mice. S-15535
      induced a similar behavioral effect to 8-OH-DPAT in SAL mice, but did not alter
      the behavior of LAL mice. Compared with LAL, forced swimming elicited in SAL mice
      a higher brain 5-HT turnover, which was potently attenuated by 8-OH-DPAT.
      CONCLUSIONS: It is unlikely that the difference in 5-HT(1A) properties between
      LAL and SAL mice is an adaptive compensatory reaction to changes in 5-HT
      metabolism. Although unspecific motor effects, at least in SAL mice, cannot be
      ruled out, it is suggested that the behavioral effects of 8-OH-DPAT and S-15535
      may be mediated by predominant activation of postsynaptic 5-HT(1A) receptors in
      LAL mice and by presynaptic 5-HT(1A) receptors in SAL mice.

PMID- 15448979
TI  - A pharmacological differentiation between postjunctional (AT1A) and prejunctional
      (AT1B) angiotensin II receptors in the rabbit aorta.
AB  - The effects of angiotensin II and angiotensin III were compared at prejunctional
      and postjunctional AT(1) receptors of the rabbit thoracic aorta. Furthermore, the
      influence of PD123319, losartan and eprosartan on these effects was also
      compared. To study prejunctional effects, the tissues were preincubated with
      ((3)H)-noradrenaline, superfused and electrically stimulated (1 Hz, 2 ms, 50 mA,
      5 min). To study postjunctional effects, non-cumulative concentration-response
      curves were determined. Both angiotensin II and angiotensin III were more potent
      prejunctionally than postjunctionally. In the case of angiotensin II, the EC(50)
      was 12 times lower at the prejunctional than at the postjunctional level, while
      that of angiotensin III was 30 times lower prejunctionally. Furthermore, whereas
      angiotensin II was about 33 times more potent than angiotensin III
      postjunctionally, it was only 12 times more potent than angiotensin III
      prejunctionally. Eprosartan did not differentiate between prejunctional and
      postjunctional effects of both angiotensins. In contrast, PD123319 and losartan
      did differentiate; however, whereas PD123319 concentration-dependently
      antagonised the facilitation of tritium release caused by angiotensin II and
      angiotensin III and had no influence on the contraction of the aortic rings
      elicited by the peptides, losartan did the opposite: it concentration-dependently
      antagonised the contractions caused by the peptides on the aortic rings and
      exerted no influence on the facilitatory effect of angiotensin II and angiotensin
      III. These results show that prejunctional and postjunctional receptors for
      angiotensin II and angiotensin III are different and underline the hypothesis
      that postjunctional AT(1) receptors belong to the AT(1A) subtype, while
      prejunctional AT(1) receptors belong to the AT(1B) subtype.

PMID- 15448980
TI  - Transforming growth factor-beta1 is not involved in TCDD-dependent release from
      contact inhibition in WB-F344 cells.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most potent tumor promoter ever
      tested in rodents. Although it is known that most of the effects of TCDD are
      mediated by binding to the aryl hydrocarbon receptor (AhR), the mechanisms
      leading to tumor promotion still remain to be elucidated. Loss of contact
      inhibition is one characteristic hallmark in tumorigenesis. In WB-F344 cells TCDD
      induces a release from contact inhibition which is manifested by a two- to
      threefold increase in DNA synthesis when TCDD (1 nM) is applied to confluent
      cells. Since proliferation of epithelial cells is known to be inhibited by TGF
      beta, we investigated whether decreased TGF-beta1 mediates TCDD-dependent release
      from contact inhibition in WB-F344 cells. Expression of TGF-beta (type II)
      receptor in WB-F344 cells was analyzed by Western blot analysis. Exposure of 0.1
      ng/ml TGF-beta1 to exponentially growing WB-F344 cells resulted in a 40% decrease
      in DNA synthesis, which was blocked by preincubation with a neutralizing anti-TGF
      beta1 antibody, indicating that the TGF-beta receptor in WB-F344 cells is
      functionally active. Preincubation of confluent, G1-arrested cultures with the
      neutralizing anti-TGF-beta1-antibody did not lead to an increase in DNA
      synthesis, ruling out an involvement of TGF-beta1 in mediating contact inhibition
      in WB-F344 cells. In accord with this, Western blot analysis revealed that
      protein expression of TGF-beta1 is neither upregulated in confluent cultures nor
      decreased after TCDD treatment. We conclude that TGF-beta1 is not involved in
      contact inhibition or in TCDD-dependent release from contact inhibition in WB
      F344 cells.

PMID- 15448981
TI  - Tobacco smoke-dependent changes in cytochrome P450 1A1, 1A2, and 2E1 protein
      expressions in fetuses, newborns, pregnant rats, and human placenta.
AB  - Tobacco smoke (TS) was described as a mixture of numerous cytochrome P450 (P450)
      substrates, inducers, and inhibitors. These inducers and inhibitors may modify
      drug clearance and xenobiotic or endogenous metabolism affecting P450s
      expression. In the present study, the effect of gestation and TS on: (1)
      cytochrome P450 CYP1A1, CYP1A2, and CYP2E1 protein expressions, and (2)
      cytochrome P450-linked microsomal enzyme activities, were studied in fetal rat
      liver, rat, and human placenta and in newborn and adult rat hepatic and
      extrahepatic tissues. Non-pregnant and pregnant 4-month-old female Wistar rats
      were exposed to TS (500, 1,000, or 1,500 mg carbon monoxide per m(3) air) in a
      toxicological chamber for 3 weeks (6 h daily, 5 days weekly). Human placentas
      were sampled from non-smoking, passive smoking, or active smoking primiparas. The
      efficacy of exposure was assessed by measuring urine cotinine levels. The TS
      dependent inductory effect on the expression of CYP1A1 and 1A2 and related
      monooxygenase activities, and the inhibitory/inductory effect on CYP2E1
      expression in rat tissues were observed. Pregnancy was associated with decreased
      levels of constitutive CYP1A1 and 2E1 in hepatic and extrahepatic tissues, TS
      inducible CYP1A2 expression in the liver, and CYP1A1 expression in lungs and
      heart, but had no inhibitory effect on TS-inducible CYP1A1 and 2E1 expression,
      EROD, and P450-cooperated enzyme activities in the liver, kidney, and, in the
      latter case, in the heart. The presence of TS-induced CYP1A1 protein was
      confirmed in rat and human placenta and showed in newborn liver and lungs. CYP1A2
      and 2E1 proteins were detectable in fetal rat liver. It was concluded that the
      expression of CYP1A1, 1A2, and 2E1, which metabolize some drugs and activate
      carcinogens, is controlled by age-, pregnancy-, and tissue-specific regulatory
      mechanisms in rats. Gestational differences in the regulation of expression of
      CYP1A subfamily members are not excluded. CYP1A1 and 2E1, but not CYP1A2
      inductory mechanisms seem to be functional in fetal liver at day 21 of pregnancy
      but they appeared to be uninducible under a TS exposure. In TS-exposed pregnant
      females and fetuses the effects of metabolic activation of CYP1A1 and 1A2
      substrates might be reduced because of lower CYP expressions or poor induction,
      respectively.

PMID- 15448982
TI  - Complementation studies of the DnaK-DnaJ-GrpE chaperone machineries from Vibrio
      harveyi and Escherichia coli, both in vivo and in vitro.
AB  - The marine bacterium Vibrio harveyi is a potential indicator organism for
      evaluating marine environmental pollution. The DnaK-DnaJ-GrpE chaperone machinery
      of V. harveyi has been studied as a model of response to stress conditions and
      compared to the Escherichia coli DnaK system. The genes encoding DnaK, DnaJ and
      GrpE of V. harveyi were cloned into expression vectors and grpE was sequenced. It
      was found that V. harveyi possesses a unique organization of the hsp gene cluster
      (grpE-gltP-dnaK-dnaJ), which is present exclusively in marine Vibrio species. In
      vivo experiments showed that suppression of the E. coli dnaK mutation by V.
      harveyi DnaK protein was weak or absent, while suppression of the dnaJ and grpE
      mutations by V. harveyi DnaJ and GrpE proteins was efficient. These results
      suggest higher species-specificity of the DnaK chaperone than the GrpE and DnaJ
      cochaperones. Proteins of the DnaK chaperone machinery of V. harveyi were
      purified to homogeneity and their efficient cooperation with the E. coli
      chaperones in the luciferase refolding reaction and in stimulation of DnaK ATPase
      activity was demonstrated. Compared to the E. coli system, the purified DnaK-DnaJ
      GrpE system of V. harveyi exhibited about 20% lower chaperoning activity in the
      luciferase reactivation assay. ATPase activity of V. harveyi DnaK protein was at
      least twofold higher than that of the E. coli model DnaK but its stimulation by
      the cochaperones DnaJ and GrpE was significantly (10 times) weaker. These results
      indicate that, despite their high structural identity (approximately 80%) and
      similar mechanisms of action, the DnaK chaperones of closely related V. harveyi
      and E.coli bacteria differ functionally.

PMID- 15448983
TI  - Identification of a region involved in the pheromone receptor function of the
      histidine kinase PlnB.
AB  - Bacteriocin biosynthesis in Lactobacillus plantarum is an inducible process,
      triggered by the secreted inducer peptide pheromone IP-C11. The environmental
      concentration of IP-C11 is monitored by the membrane-bound histidine protein
      kinase PlnB, which is part of a two-component signal transduction pathway. Upon
      interaction with IP-C11, PlnB phosphorylates the cognate response regulator PlnC.
      This regulator subsequently activates transcription of the bacteriocin genes.
      PlnB belongs to the HPK(10) subfamily of peptide-pheromone-activated histidine
      kinases. All members of this subfamily have an unusual polytopic membrane domain
      that previously has been shown to contain the peptide pheromone receptor.
      Employing an in vivo reporter assay, the present work investigated the receptor
      functionality of various mutagenized PlnB membrane domains. The results indicated
      that important determinants for receptor function locate to the most N-terminal
      extracytoplasmatic loop of the membrane domain. In addition, this region appears
      to be involved in the peptide pheromone interaction of ComD, another member of
      the HPK(10) subfamily.

PMID- 15448984
TI  - Bone mineral density measurement in the calcaneus with DXL: comparison with hip
      and spine measurements in a cross-sectional study of an elderly female
      population.
AB  - We investigated the relationship between calcaneal and axial bone mineral density
      in an elderly female population. We also investigated the influence of changing
      the reference populations on T-score values. Bone mineral density (BMD) was
      determined in 388 women (mean age 73 years) participating in a cross-sectional
      study. BMD values were determined at the left hip and the lumbar spine, L1-L4,
      using Hologic QDR 4500 equipment for dual X-ray absorptiometry (DXA). The
      calcaneal measurements were made with DEXA-T, a device using a dual X-ray and
      laser (DXL) technique that combines DXA measurement with measurement of the heel
      thickness using a laser reflection technique. DEXA-T is an older version of the
      Calscan DXL device now commercially available. T-score values were calculated for
      hip measurements with both the original reference population of the Hologic
      device and the NHANES III reference population. T scores for heel measurements
      were calculated with the original reference population of the peripheral device
      and the Calscan database, a new calcaneal reference population. Changing the
      reference populations had a great influence on both the heel and the hip T
      scores, especially those of the femoral neck where the percentage of subjects
      identified as osteoporotic decreased from 53% to 23%. We conclude that, with the
      NHANES III and the larger Calscan database, using the cut-off point of -2.5 SD,
      the heel measurements had optimal accuracy for detecting osteoporosis at either
      the combination of the lumbar spine and the femoral neck or the combination of
      the lumbar spine, the femoral neck, the total hip and the trochanter. BMD
      measurements of the calcaneus with DXL correlated fairly well with measurements
      at axial sites at the group level, while in individual subjects large deviations
      were observed between all the measured sites. We also conclude that the influence
      of the reference populations on the T scores is substantial when different DXA
      methods are being compared; the total number of subjects classified as
      osteoporotic varied from 7% to 53% between the sites and with different reference
      populations.

PMID- 15448985
TI  - Meta-analysis of the efficacy of alendronate for the prevention of hip fractures
      in postmenopausal women.
AB  - Treatment with alendronate, a potent and specific inhibitor of bone resorption,
      is known to significantly reduce fracture risk among women with postmenopausal
      osteoporosis. The purpose of this meta-analysis was to assess the consistency of
      the effect of alendronate in reducing the risk of hip fracture among different
      studies and populations. Data from completed, randomized, treatment studies were
      pooled in a meta-analysis. The duration of the studies ranged from 1-4.5 years.
      The dose of alendronate ranged from 5-20 mg/day, with over 95% of patients
      receiving either 5 or 10 mg/day during the trials. In patients with a T-score of
      less than or equal to -2.0, or with a vertebral fracture, the effect on hip
      fracture risk consistently favored patients receiving alendronate therapy, with
      an overall reduction in risk of hip fracture of 45% [95% confidence interval (CI)
      16% to 64%, P=0.007]. For patients who met the criteria of osteoporosis, as
      defined by the World Health Organization (WHO), the overall risk reduction was
      55% (95% CI 29% to 72%, P=0.0008). In both analyses we performed a sensitivity
      analysis by removing one study at a time. The strength of the evidence was not
      dependent on any one study. We conclude that therapy with alendronate is
      associated with significant and clinically important reductions in the incidence
      of hip fracture in women with postmenopausal osteoporosis. The overall reduction
      is consistent among different patient populations.

PMID- 15448986
TI  - Forearm bone mineral density in an unselected population of 2,779 men and women-
      the HUNT Study, Norway.
AB  - The fracture incidence in Norway is among the highest in Europe, presumably due
      to osteoporosis. As part of a multipurpose health study in the county of Nord
      Trondelag, Norway (the HUNT study), a 5% randomly selected sample (n=4,646) of
      the population >19 years of age was invited to undergo single X-ray
      absorptiometry (SXA) of the forearm. A total of 1,274 men (50.5 years) and 1,505
      women (49.9 years) participated (60%). The aim of the study was to describe the
      variation in bone mineral density (BMD) and the prevalence of forearm BMD 2.5
      standard deviations (SD) below the mean value for young adults in an unselected
      population sample. In women the BMD remained stable until the age of 50 years,
      whereupon a strong decline in BMD was observed. In men, a BMD increase was
      observed until about the age of 40 years; the decline after the age of 65 was,
      however, similar to that in women. Based on age and gender-specific reference
      values, the age-adjusted prevalence of T-scores <-2.5 SD in women and men aged 50
      69 years was 16.0% and 5.6%, respectively. In the age group of 70 years or older
      the prevalence was 65.8% and 30.6% for women and men, respectively. The
      accelerated BMD reduction in women aged 50-65 explains the higher prevalence of T
      score <-2.5 SD in elderly women than in men. Further studies on bone loss and
      falls are required to explain the high fracture incidence in Norway.

PMID- 15448987
TI  - Prevalence of osteoporosis in men and determinants of changes in bone mass in a
      non-selected Spanish population.
AB  - Osteoporotic studies conducted exclusively in men have been limited by the
      discrepancies in defining densitometric osteoporosis and, also, because
      osteoporosis has traditionally been associated only with women. The aims of this
      study were to describe the prevalence of low bone mineral density (BMD) and
      osteoporotic fractures as well as the rate of bone loss. The analysis of some
      risk factors for accelerated bone loss was also evaluated. Men aged 50 years and
      over, randomly selected from the Oviedo municipal register (n = 308), completed a
      questionnaire regarding risk factors related to osteoporosis; they underwent two
      lateral radiographs of the dorsal and lumbar spine and a dual X-ray
      absorptiometry (DXA) study at the lumbar spine and hip. In the 4th year of the
      follow-up period, participants were invited to undergo repeats of the same tests
      that had been carried out in the initial study. The prevalence of densitometric
      osteoporosis in men older than 50 years, standardized by age, was 8.1% with
      regard to at least one of the four studied bone areas, with a slight increase
      with age. The prevalence of osteoporotic fracture, standardized by age, was
      24.4%, with a marked increase with age. Osteoporotic prevalent fracture was
      independently associated only with the rate of change in lumbar spine BMD. From
      all the osteoporotic risk factors analyzed, only low milk consumption and regular
      smoking were independently associated with loss of bone mass. In summary,
      prevalent osteoporotic fracture was independently associated with the rate of
      change in the lumbar spine BMD but not in the other segments studied. Avoiding
      smoking and ensuring an adequate milk intake might prevent the loss of bone mass
      in men.

PMID- 15448988
TI  - Depression and bone mineral density: is there a relationship in elderly Asian
      men? Results from Mr. Os (Hong Kong).
AB  - Previous epidemiological study has suggested that depression might be associated
      with low bone mass in Caucasian women. This has not been studied in Asian men.
      Mr. Os (Hong Kong) is the first, large, cohort study on osteoporosis in Asian
      men, and the current analysis deals with the association between depression and
      bone mass in this group. Data from the baseline examination of Mr. Os (Hong Kong)
      were used. Two thousand Hong Kong men aged 65 to 92 years were recruited from the
      community. Depression was diagnosed by face-to-face interview, using a validated
      Chinese version of the Geriatric Depression Scale (GDS), with depression being
      defined as a cut-off score of 8 or more. Bone mineral density (BMD) of the lumbar
      spine, total hip and total body was measured by dual X-ray densitometry (DEXA)
      using the Hologic QDR-4500 W densitometer. Multiple regression was used to
      compare BMD in depressed and non-depressed subjects, controlling for confounding
      variables. In the study sample 8.5% of men were found to be depressed, and the
      BMD at the total hip in these subjects was 2.1% lower than in non-depressed
      subjects (95% CI -0.13 to -4.1), after adjustment for age, body weight, medical
      history, alcohol consumption, cigarette smoking, calcium intake, physical
      activity and antidepressant use. Depression was associated with a 1.4-fold (95%
      CI 1.00 to 2.08) relative risk (RR) of being diagnosed with a T-score equal to or
      less than -1.0 (low bone mass). We conclude that depression is associated with
      lower BMD; however, to determine whether depression causes lower BMD or vice
      versa, we will need to await findings from future prospective studies.

PMID- 15448989
TI  - Vitamin D insufficiency in adolescent males in Southern Tasmania: prevalence,
      determinants, and relationship to bone turnover markers.
AB  - There are limited data on vitamin D insufficiency in healthy children. The aim of
      this study was to describe the prevalence and determinants of vitamin D
      insufficiency and its association with bone turnover in adolescent boys (N = 136,
      mean age 16 years). Sun exposure and physical activity were assessed by
      questionnaire. Vitamin D stores were assessed by serum 25-hydroxyvitamin D3
      (25[OH]D3). Bone turnover was assessed by bone-specific alkaline phosphatase
      (BAP) and urinary pyridinoline (PYR) to creatinine (Cr) ratio (mmol PYR/micromol
      Cr). The mean 25(OH)D3 level was low (44 nmol/l; 68% < 50 nmol/l; range, 16-87)
      and was associated with self-reported sun exposure on winter weekends (r = 0.23,
      p = 0.01), school holidays (r = 0.22, p = 0.01), and weekdays (r = 0.17, p =
      0.05). It was also associated with number of sports (r = 0.34, p < 0.001) and
      vigorous activity (r = 0.22, p = 0.01) but not television, computer, and video
      watching (r = -0.04, p = 0.68). In multivariate analysis, number of sports but
      not total sun exposure remained significantly associated with 25(OH)D3.
      Furthermore, 25(OH)D3 was significantly associated with BAP in cutpoint analysis
      (cutpoint 55 nmol/l, p = 0.03) but not continuous analysis (r = -0.12, p = 0.16)
      and PYR in both forms (r = -0.23, p = 0.01, cutpoint 43 nmol/l, p = 0.01). In
      conclusion, vitamin D insufficiency is common in healthy adolescent boys in
      winter in our setting, is primarily derived from sports-related sun exposure, and
      is associated with bone turnover markers. These data suggest that a 25(OH)D3
      level of at least 43-55 nmol/l is required for optimal bone health in children.

PMID- 15448991
TI  - [RPE transplantation: the challenges and the future].
AB  - Transplantation of RPE cells represents a potential therapeutic intervention for
      various retinal degenerations including complex, multifactorial age-related
      macular degeneration (AMD). Prerequisite for a successful RPE transplantation is
      the isolation of suitable cells, which must establish themselves in the host eye
      to develop functionality similar to that of healthy RPE cells in vivo. Autologous
      cells can be harvested from the peripheral retina. Ex vivo gene manipulation
      offers the possibility that even a dysfunctional donor RPE cell can be restored
      to perform a required specific function in the retina which may in turn help
      prevent or slow down the degenerative process in the host eye. The problem of
      cultured RPE cells is that they lose many of their normal phenotypic
      characteristics, which also leads to a reduction of their functional capacity.
      Currently highly "stressed" RPE cells are transplanted, whether fresh or
      cultured, which may not establish their normal in vivo functions. The generation
      of a genetically engineered cell line with all the functions of a healthy RPE
      cell and the use of retinal stem cells represent alternative and promising
      approaches for the future.

PMID- 15448992
TI  - [Oculomandibular dyscrania. 5-year-old girl with congenital cataract and
      glaucoma].

PMID- 15448993
TI  - [Bilateral keratitis in lagophthalmos and lower lid ectropion].

PMID- 15448994
TI  - Efficacy of routine follow-up after first-line treatment for testicular cancer.
AB  - To define guidelines for the follow-up management of patients treated for
      testicular germ cell tumor this study assessed characteristics of patients with
      recurrent disease. The charts of 505 patients with testicular cancer treated and
      followed-up at the University Medical Centre Nijmegen between 1982-2000 were
      reviewed retrospectively. In 42 patients disease recurrence was found during
      routine follow-up. In a subset of patients no recurrences were seen after first
      line treatment: (a) pathological stage IIa nonseminoma patients who were
      adjuvantly treated with chemotherapy and (b) histologically confirmed complete
      responders after primary chemotherapy. Furthermore, in low-stage disease no intra
      abdominal recurrences were seen in (a) pathological stage I nonseminoma patients
      and (b) low-stage seminoma patients who received radiotherapy. The risk of
      recurrent testicular cancer depends on primary therapy and efficacy of it; these
      results indicate a limited role for follow-up in pathological stage II
      nonseminoma patients adjuvantly treated with chemotherapy and in histologically
      confirmed complete responders after chemotherapy. Abdominal computed tomography
      does not appear necessary in routine follow-up of patients treated for low-stage
      testicular cancer.

PMID- 15448995
TI  - Ileal conduit urinary diversion in patients with previous history of
      abdominal/pelvic irradiation.
AB  - Urinary diversion among patients receiving prior radiation is common. Herein, we
      present our experience with ileal conduit (IC) diversion in patients with a
      history of prior abdominal and/or pelvic radiation therapy. We analyzed the
      charts of 177 patients who underwent IC urinary diversion between 1/1994 and
      6/2000, and 36 patients were identified who had previously undergone radiation
      therapy. Decisions to proceed were based on surgeon preference as determined by
      intraoperative appearance and viability of the selected bowel segment. Chart
      review included serum studies, upper tract imaging studies, and complications
      related to diversion. Durability of diversion was determined by examining the
      interval between urinary diversion and the need for additional procedures. A
      total of 30 patients with at least 3 months follow-up were identified. Renal
      function remained stable in 86% (26/30) with a median follow-up of 21.5 months
      (range 3-63 months). Hydronephrosis was noted preoperatively in 4 patients (13%)
      who demonstrated stable upper tracts and serum creatinine in the post-operative
      period. Three patients (10%) developed unilateral hydronephrosis related to tumor
      recurrence, with one patient demonstrating a rise in baseline serum creatinine.
      Hydronephrosis was noted in 5 patients (16%) secondary to development of
      ureteroenteric stricture. Serum creatinine remained stable in 2 patients without
      intervention with 2 years follow-up. Intervention for obstruction was necessary
      in 3 patients at 22, 31, and 61 months following diversion. In one patient, an
      intraoperative decision to use the colon for urinary diversion was made secondary
      to appearance of small bowel. Minor complications were noted in 9 patients (30%),
      while 3 patients (10%) experienced major complications in the immediate post
      operative period. Five patients (17%) experienced complications potentially
      related to the use of ileum for urinary diversion. The use of ileum for urinary
      diversion among patients with a history of radiation appears technically feasible
      and a viable treatment alternative. Our data support the use of ileum in the
      majority of patients as evidence by a low complication rate and a high rate of
      upper tract preservation. In addition, these data imply that a prior history of
      abdominal and/or pelvic radiation should not serve as the sole determining factor
      in the selection of bowel segment utilized during urinary diversion.

PMID- 15448996
TI  - Induction of apoptosis in human prostate stromal cells by 4-hydroxytamoxifen: an
      alternative therapy for benign prostate hyperplasia.
AB  - Benign prostate hyperplasia (BPH) is a disease of the aging male. In BPH, the
      imbalance of cell proliferation and programmed cell death (apoptosis) leads to
      continuous stromal growth. Common medication interrupts stromal cell
      proliferation but has only little effect on inducing stromal cell apoptosis. In
      this study, we investigated tamoxifen (TAM) and 4-hydroxytamoxifen (OHT) for
      their ability to induce apoptosis in human prostate stromal cells (PrSC) in
      vitro. After the incubation of PrSC with different concentrations of TAM or OHT,
      the cytotoxic effect was measured using an MTT-assay. The induction of apoptosis
      after OHT treatment was investigated by FACS-analysis (annexin V FITC staining)
      and Western blot (PARP-1 cleavage, BCL-2 and BAX-alpha expression). The
      administration of TAM at concentrations of 0-20 microM had very little effect on
      cell viability as measured by MTT assay. In contrast, the use of 10-20 microM OHT
      led to a significant decrease in cell viability. The binding of annexin V FITC to
      apoptotic cells was demonstrated by FACS-analysis. The induction of apoptosis was
      further proven by Western blot of PARP-1 protein cleavage and the expression of
      the anti-apoptotic BCL-2 and the pro-apoptotic BAX-alpha proteins. In conclusion,
      our data clearly demonstrate, that the administration of OHT at concentrations
      from 10-20 microM induced apoptosis in human PrSC. The more effective induction
      of apoptosis with OHT compared with TAM could very well explain the results of
      clinical studies showing no clinical effect of TAM treatment on BPH. Furthermore,
      our results, if reproducible in vivo, could open new avenues for the treatment of
      BPH by local administration of OHT in apoptosis-inducing concentrations.

PMID- 15448997
TI  - Percutaneous nephrolithotomy in children: experience with 138 cases in a
      developing country.
AB  - Our aim was to evaluate our experience with percutaneous nephrolithotomy (PCNL)
      in children in the Republic of Yemen. Between January 1993 and December 1998, 135
      children underwent 138 percutaneous nephrolithotomies in Yemen. The patient's age
      ranged between 8 months and 14 years (average 8.9 years). There were 117 boys and
      18 girls (male:female ratio 6.5:1). The stone size ranged between 124 and 624 mm2
      (average 507 mm2). A 26 F adult nephroscope was used. The stone free rate was
      98.5% (136 out of the 138 cases). Two patients had clinically insignificant
      fragments. A second session had to be performed because of residual stone in one
      patient. No severe intra- or postoperative complications were observed. We
      conclude that percutaneous nephrolithotomy is a safe and effective method for the
      treatment of kidney stones in children. It reduces morbidity and hospital stay
      and thus the cost of treatment. To our knowledge, this is the largest reported
      series.

PMID- 15448998
TI  - Distinguishing pelvic phleboliths from distal ureteral calculi: thin-slice CT
      findings.
AB  - The objective is to evaluate the appearance of phleboliths and distal ureteral
      stones by determining their roundness and presence of central lucency on thin
      slice CT. Seventy-seven patients with pelvic radioopacities at unenhanced CT were
      selected. Those patients consequently underwent thin-slice CT with 1-mm
      collimation, a FOV of 10 cm, a pitch of 1:1 and a bone reconstruction algorithm.
      Three radiologists reviewed all images for roundness and the presence of central
      radiolucency. No calculi showed central lucency on either imaging technique used.
      Thin-slice CT revealed central lucency in 60% of phleboliths with 100%
      specificity. Three of 40 ureteral stones showed round contour. Thin-slice CT
      revealed a round contour in 97% of phleboliths with 93% specificity. Central
      lucency is a characteristic finding of pelvic phleboliths on thin-slice CT. This
      finding can therefore be used in combination with roundness as a problem-solving
      tool in differentiating phleboliths from distal ureteral stones.

PMID- 15448999
TI  - Adrenal gland and adrenal mass calcification.
AB  - With the widespread use of computed tomography (CT), it is not unusual to find
      calcification within the adrenal glands. There are a variety of adrenal lesions
      that may calcify, but usually the appearance of the calcification is not
      specific. However, when the pattern and morphology of the adrenal calcification
      are combined with the other imaging features and the appropriate clinical
      history, the correct diagnosis may be suggested.

PMID- 15449000
TI  - Detection of hepatocellular carcinoma: comparison of ferumoxides-enhanced and
      gadolinium-enhanced dynamic three-dimensional volume interpolated breath-hold MR
      imaging.
AB  - The purpose was to compare the diagnostic accuracy of ferumoxides-enhanced MR
      imaging and gadolinium-enhanced dynamic MR imaging using three-dimensional (3D)
      volume interpolated breath-hold examination (VIBE) for the detection of
      hepatocellular carcinoma (HCC). Forty-nine patients with 61 HCCs, who underwent
      ferumoxides-enhanced and gadolinium-enhanced dynamic MR imaging, were included
      prospectively in this study. Ferumoxides-enhanced MR imaging was performed 24 h
      after completion of the dynamic study using 3D-VIBE. Three radiologists
      independently interpreted the images. The diagnostic accuracy was evaluated using
      the receiver-operating characteristic method, and the sensitivity of each imaging
      technique was compared using McNemar's test. The mean diagnostic accuracy of
      dynamic MR imaging (Az=0.95) was higher than that of ferumoxides-enhanced MR
      imaging (Az=0.90), but failed to reach a statistical significance (P=0.057). The
      mean sensitivity of dynamic MR imaging (90.7%) was significantly superior to that
      of ferumoxides-enhanced MR imaging (80.9%, P=0.03). Furthermore, for lesions
      smaller than 15 mm, the mean sensitivity of dynamic MR imaging was significantly
      higher than that of ferumoxides-enhanced MR imaging (85.2% vs. 69.2%, P<0.05).
      Dynamic MR imaging showed a trend toward better diagnostic accuracy for than
      ferumoxides-enhanced MR imaging for the detection of HCCs.

PMID- 15449001
TI  - Multidetector computed tomography-guided treatment strategy in patients with non
      ST elevation acute coronary syndromes: a pilot study.
AB  - Patients with non-ST elevation acute coronary syndrome (ACS) and evidence of
      myocardial ischaemia are scheduled for coronary angiography (CAG). In most
      patients CAG remains a single diagnostic procedure only. A prospective study was
      performed to evaluate whether 16-slice multidetector CT (MDCT) could predict
      treatment of the patients and to determine how many CAGs could have been
      prevented by MDCT scanning prior to CAG. Twenty-two patients with ACS were
      scanned prior to CAG. Based on MDCT data, a fictive treatment was proposed and
      compared to CAG-based treatment. Excellent accuracy was observed to detect
      significant stenoses using MDCT (sensitivity 94%, specificity 96%). In 45%, no
      PCI was performed during CAG, because of the absence of significant coronary
      artery disease (27%) or severe coronary artery disease, demanding CABG (18%).
      MDCT predicted correct treatment in 86%. By using MDCT data, 32% of the CAGs
      could have been prevented.

PMID- 15449003
TI  - The fibrocartilage sesamoid.

PMID- 15449004
TI  - Quantification of C2 cervical spine rotatory fixation by X-ray, MRI and CT.
AB  - Atlanto-axial rotatory displacement is known to be a cause of childhood
      torticollis and may as well be responsible for chronic neck pain after rear-end
      automobile collisions. The objective was to determine whether quantification of
      C2 malrotation is possible by plain radiographs in comparison to CT as the golden
      standard. MR imaging was evaluated as to whether it was of equal value in the
      detection of bony landmarks. C2 vertebra of five human cadaveric cervical spine
      specimens, ligamentously intact, were rotated using a Steinmann pin in steps of 5
      degrees up to 15 degrees right and 15 degrees left. Plain radiographs, CT and MRI
      images were taken in each rotational step. Data were analyzed for quantification
      of C2 rotation by three independent examiners. A rotation of 5 degrees led to a
      spinous process deviation (SPD) from the midline of 3 mm as measured on an a.p.
      plain radiograph. A coefficient of rotation was calculated (1.62 degrees mm(-1)).
      Data analyzed by three examiners revealed a small coefficient of variation
      (0.03). MRI and CT measurements showed comparable results for the quantification
      of rotation; however, in both techniques the 15 degrees rotation was
      underestimated. Quantification of upper cervical spine malrotation was possible
      on plain radiographs using the SPD and a rotation coefficient. MRI and CT were
      equally successful in the assessment of C2 malrotation.

PMID- 15449005
TI  - Differential diagnosis of tumours and tumour-like lesions of the infrapatellar
      (Hoffa's) fat pad: pictorial review with an emphasis on MR imaging.
AB  - A variety of intrinsic and extrinsic tumours and tumour-like conditions may
      affect the infrapatellar (Hoffa's) fat pad (IFP). MR imaging is the technique of
      choice in evaluating these conditions, but correlation with radiographs is
      important to identify those lesions producing mineralization. This pictorial
      review illustrates the spectrum of mass-like lesions that can affect the IFP,
      emphasizing the radiographic and MR findings that suggest a specific diagnosis.

PMID- 15449006
TI  - Robot-assisted biopsy using ultrasound guidance: initial results from in vitro
      tests.
AB  - The purpose of this study was to develop a robotic system for ultrasound (US)
      guided biopsy and to validate the feasibility, accuracy and efficacy using
      phantom tests. Twenty peas (mean diameter 9.3+/-0.1 mm) embedded within a gel
      phantom were selected for biopsy. Once the best access was defined, the position
      of the US transducer was recorded by an optical tracking system. Positional data
      of the transducer and the corresponding US image were transferred to the roboter
      planning system (LINUX-based industrial PC equipped with video capture card).
      Once the appropriate position, angulation and pitch were calculated, the robotic
      arm moved automatically with seven degrees-of-freedom to the planned insertion
      path, aiming the needle-positioning unit at the center of the target. Then, the
      biopsy was performed manually using a coaxial technique. The length of all
      harvested specimens was measured, and the deviation of the actual needle tract
      from the center of the target was evaluated sonographically. In all targets, the
      biopsy specimen (mean length 5+/-1.2 mm) was harvested with only one needle pass
      required The mean deviation of the needle tip from the center of the target was
      1.1+/-0.8 mm. Robotic assisted biopsies in-vitro using US-guidance were feasible
      and provided high accuracy.

PMID- 15449007
TI  - Application of an exogenous hyperoxic contrast agent in MR mammography: initial
      results.
AB  - There is interest in applying novel methods to dynamic MR mammography (MRM). One
      such possibility is to administer an exogenous hyperoxic contrast agent, such as
      carbogen (95-98% O2 and 2-5% CO2) or pure oxygen (100% O2). We report our first
      experiences with these agents in a patient with an invasive lobular carcinoma.
      Fourteen dynamic series were acquired with an rf-spoiled 2D multislice gradient
      echo sequence, including three measurements while breathing air, four
      measurements with 100% oxygen, three measurements with air and four measurements
      with carbogen. Afterwards, 0.1 mmol/kg bw of Gd-DTPA was administered to obtain
      dynamic T1-weighted double-echo 3D axial gradient echo images
      (TR/TE1/TE2/alpha=7.8 ms/2 ms/4.76 ms/15 degrees) every 90 s up to 4.5 min after
      injection. The lesion was well delineated on the contrast-enhanced images,
      contrary to magnitude images reconstructed from the raw data sets acquired during
      air/oxygen/carbogen breathing. A ROI-based median-filtered signal-time course
      revealed a tumor signal increase of roughly 15% between scans acquired during air
      and oxygen breathing. Though preliminary, these first results are encouraging
      concerning the exploration of these alternative contrast agents in MRM in greater
      detail.

PMID- 15449008
TI  - Dynamic echo-planar MR imaging of the diaphragm for a 3D dynamic analysis.
AB  - The purpose of this study was to prove the feasibility of 3D reconstructions of
      the diaphragm during the respiratory cycle using EPI sequences (EPI acquisition,
      270 ms/image, on a healthy subject breathing spontaneously and at 0.1 Hz).
      Continuously recorded respiratory signal allowed for retrospective
      synchronization with respiratory phases for reconstruction of successive
      diaphragm surfaces using a specifically designed software. Displacements, area
      and volume changes of the diaphragm were quantified. Our measurements were
      comparable with the data in the literature. Reconstructed surfaces allowed in
      vivo diaphragm dynamic evaluation in terms of displacements, area and volume
      variations. EPI has adequate spatial and temporal resolution for studying
      diaphragm dynamics during natural breathing.

PMID- 15449009
TI  - Improved diagnosis of vascular dissection by ultrasound B-flow: a comparison with
      color-coded Doppler and power Doppler sonography.
AB  - The purpose was to evaluate the diagnostic results of different ultrasound
      techniques: color-coded Doppler (CCD), power Doppler (PD) and B-flow in the
      diagnosis of vascular dissection. Findings from 68 patients with arterial
      dissection proven either by vascular ultrasound (US) or by magnetic resonance
      angiography (MRA), computed tomographic angiography (CTA) or intra-arterial
      digital subtraction angiography (DSA) were reviewed in retrospect. The study
      compared results from three different modes of ultrasound, i.e., CCD, PD and B
      flow, in dissections of the carotid artery (n=11), of the vertebral artery (n=9),
      of the abdominal aorta (n=13), of the iliac artery (n=12) and of the femoral
      artery (n=23). MRA, CTA and DSA were considered as reference standard. The
      sensitivity of CCD for detecting all dissections was 78%, 84% for the PD and 98%
      for B-flow. For carotid artery dissection, the sensitivity of CCD, PD and B-flow
      was 82, 91 and 98%, for the vertebral artery 67, 78 and 98%, for the abdominal
      aorta 85, 85 and 98%, for the iliac artery 67, 75 and 98%, for the femoral artery
      83, 87 and 98%, respectively. Intima flaps, fissures of membranes and residual
      flow within the true and false lumen were better detected by B-flow than by CCD
      and PD. The lack of angle dependence of the US probe in B-flow made the
      examination procedure easier. In the cine mode of B-flow, the pulse synchronic
      movement of the membrane was more apparent than in any other imaging method. With
      B-flow, accuracy for the diagnosis of arterial dissection is improved compared to
      CCD and PD. Flow within the true and false lumen, low-echo thrombi, intramural
      hematoma and even movements of the dissection membrane are clearly distinguished.

PMID- 15449010
TI  - CT findings in severe thoracic sarcoidosis.
AB  - Severe thoracic sarcoidosis includes manifestations with significant clinical and
      functional impairment and a risk of mortality. Severe thoracic sarcoidosis can
      take on various clinical presentations and is associated with increased
      morbidity. The purpose of this article was to describe the CT findings in severe
      thoracic sarcoidosis and to explain some of their mechanisms. Subacute
      respiratory insufficiency is a rare and early complication due to a high
      profusion of pulmonary lesions. Chronic respiratory insufficiency due to
      pulmonary fibrosis is a frequent and late complication. Three main CT patterns
      are identified: bronchial distortion, honeycombing and linear opacities. CT can
      be helpful in diagnosing some mechanisms of central airway obstruction such as
      bronchial distortion due to pulmonary fibrosis or an extrinsic bronchial
      compression by enlarged lymph nodes. An intrinsic narrowing of the bronchial wall
      by endobronchial granulomatous lesions may be suggested by CT when it shows
      evidence of bronchial mural thickening. Pulmonary hypertension usually occurs in
      patients with end-stage pulmonary disease and is related to fibrotic destruction
      of the distal capillary bed and to the resultant chronic hypoxemia. Several other
      mechanisms may contribute to the development of pulmonary hypertension including
      extrinsic compression of major pulmonary arteries by enlarged lymph nodes and
      secondary pulmonary veno-occlusive disease. Aspergilloma colonization of a cavity
      is the main cause of hemoptysis in sarcoidosis. Other rare causes are
      bronchiesctasis, necrotizing bronchial aspergillosis, semi-invasive pulmonary
      aspergillosis, erosion of a pulmonary artery due to a necrotic sarcoidosis
      lesion, necrosis of parenchymal sarcoidosis lesions and specific endobronchial
      macroscopic lesions.

PMID- 15449011
TI  - Functional MR imaging of submandibular herniation of sublingual tissues through a
      gap of the mylohyoid muscle in two cases of submandibular "masses".
AB  - Except for neoplasms, in symptomatic patients with submandibular swellings, gaps
      of the mylohyoid muscle may be the cause of herniations of sublingual tissues,
      such as fat and/or the sublingual gland. In two patients with a submandibular
      swelling, MRI with standard sequences including contrast enhancement was
      performed to exclude a neoplastic lesion. In addition, we performed a trueFISP
      sequence during modified Valsalva's maneuver. In both patients, a neoplasm was
      excluded. Instead, the trueFISP sequence during the modified Valsalva's maneuver
      showed submandibular herniation of sublingual tissues. If MRI of the floor of the
      mouth does not show a neoplasm, an additional functional MR investigation should
      be performed. Gaps of the mylohyoid muscle can be the cause of herniating
      sublingual tissues (similar to plunging ranulas). During the modified Valsalva's
      maneuver, sublingual fat and/or gland can herniate and cause a symptomatic
      submandibular swelling. A coronal trueFISP sequence is particularly suited to
      demonstrate this.

PMID- 15449012
TI  - Phase- and size-adjusted CT cut-off for differentiating neoplastic lesions from
      normal colon in contrast-enhanced CT colonography.
AB  - A computed tomography (CT) cut-off for differentiating neoplastic lesions
      (polyps/carcinoma) from normal colon in contrast-enhanced CT colonography (CTC)
      relating to the contrast phase and lesion size is determined. CT values of 64
      colonic lesions (27 polyps <10 mm, 13 polyps > or =10 mm, 24 carcinomas) were
      determined by region-of-interest (ROI) measurements in 38 patients who underwent
      contrast-enhanced CTC. In addition, the height (H) of the colonic lesions was
      measured in CT. CT values were also measured in the aorta (A), superior
      mesenteric vein (V) and colonic wall. The contrast phase was defined by xA + (1
      x)V using x as a weighting factor for describing the different contrast phases
      ranging from the pure arterial phase (x=1) over the intermediate phases (x=0.9
      0.1) to the pure venous phase (x=0). The CT values of the lesions were correlated
      with their height (H), the different phases (xA+(1-x)V) and the ratio [xA+(I
      x)V]/H. The CT cut-off was linearly adjusted to the imaged contrast phase and
      height of the lesion by the line y=m[xA+(1-x)V]H+y(0). The slope m was determined
      by linear regression in the correlation (lesion approximately [xA+(i-x)V]/H) and
      the Y-intercept y(0) by the minimal shift of the line needed to maximize the
      accuracy of separating the colonic wall from the lesions. The CT value of the
      lesions correlated best with the intermediate phase: 0.4A + 0.6V (r=0.8 for
      polyps > or =10 mm, r=0.6 for carcinomas, r=0.4 for polyps <10 mm). The accuracy
      in the differentiation between lesions and normal colonic wall increased with the
      height implemented as divisor, reached 91% and was obtained by the dynamic cut
      off described by the formula: cut-off (A,V,H)=1.1 [0.4A+0.6V]/H+69.8. The CT
      value of colonic polyps or carcinomas can be increased extrinsically by scanning
      in the phase in which 0.4A + 0.6V reaches its maximum. Differentiating lesions
      from normal colon based on CT values is possible in contrast-enhanced CTC and
      improves when the cut-off is adjusted (normalized) to the contrast phase and
      lesion size.

PMID- 15449013
TI  - Aplasia of the N. cochlearis with retrocochlear deafness: the role of thin-slice
      3D T2-weighted imaging.

PMID- 15449014
TI  - Rectal metastasis from infiltrating lobular breast carcinoma: imaging with 18F
      FDG PET.

PMID- 15449015
TI  - Consistent and stable expression of the nptII, uidA and bar genes in transgenic
      Pinus radiata after Agrobacterium tumefaciens-mediated transformation using nurse
      cultures.
AB  - An Agrobacterium tumefaciens-mediated transformation protocol has been developed
      for embryogenic cell cultures of Pinus radiata. Transgenic lines were only
      produced when embryogenic tissue was placed on nurse tissue during the
      Agrobacterium co-cultivation and recovery stages of the procedure. Plantlets were
      regenerated via somatic embryogenesis from ten of the 11 transgenic lines tested
      and at least 20 of each line were planted in a GMO glasshouse. Expression of the
      nptII, uidA and bar genes in up to ten plants of each individual transgenic line
      was evaluated by molecular, biochemical and functional analysis. As expected,
      expression of the nptII gene varied among the ten lines, while within ten
      replicates of the same line, nptII expression appeared to be consistent, with the
      exception of one line, K3. Likewise, the level of GUS activity varied among
      transgenic lines, but was relatively consistent in plants derived from the same
      tissue, except for two lines, G4 and G5. Moreover, similar absolute values and
      pattern of gene expression of uidA was observed in the transgenic plants, for two
      consecutive years. Plantlets from eight lines survived a spray treatment with the
      equivalent of 2 kg/ha and 4 kg/ha of the commercial formulation Buster, whereas
      non-transformed controls died. Southern hybridisation analysis of embryogenic
      tissue and green needle tissue from putative transgenic lines demonstrated a
      relatively low number of gene insertions (from one to nine) of both the bar and
      nptII genes in the nine transgenic lines tested.

PMID- 15449016
TI  - Green fluorescent protein as a vital elimination marker to easily screen marker
      free transgenic progeny derived from plants co-transformed with a double T-DNA
      binary vector system.
AB  - We investigated the potential of a novel double T-DNA vector for generating
      marker-free transgenic plants. Co-transformation methods using a double T-DNA
      vector or using mixture of two Agrobacterium tumefaciens strains were compared,
      and showed that the double T-DNA vector method could produce marker-free
      transgenic tobacco (Nicotiana tabacum L.) plants more efficiently. A dual marker
      double T-DNA vector was then constructed by assembling the green fluorescent
      protein (GFP) gene mgfp5 and the neomycin phosphotransferase gene nptII into the
      same T-DNA. The frequency of co-transformants produced by this vector was 56.3%.
      Co-expression of mgfp5 and nptII was found in 28 out of 29 T1 lines, and
      segregation of the reporter beta-glucuronidase gene, gusA, from mgfp5 to nptII
      was found in 12 out of 29 T1 lines. Therefore, GFP could be used as a vital
      marker to improve the transformation efficiency and to easily monitor the
      segregation of marker genes, thus facilitating screening of marker-free progeny.

PMID- 15449017
TI  - A metabolomic analysis of medicinal diversity in Huang-qin (Scutellaria
      baicalensis Georgi) genotypes: discovery of novel compounds.
AB  - In vitro manipulation of plant regeneration in the Chinese medicinal species
      Scutellaria baicalensis Georgi (Huang-qin) resulted in 26 chemically distinct
      germplasm lines. Antioxidant potential, growth rate and concentration of
      baicalin, baicalein, melatonin, and wogonin were the selective markers used to
      identify elite lines. Metabolomic analysis of a subset of the most distinct lines
      revealed that Huang-qin extracts contained over 2,000 compounds including 781
      determined to be of putative medicinal importance as determined by a database
      search, as well as previously unidentified amino-derivatives of baicalin and
      wogonin. Huang-qin also contained a metabolite with the same net formula as
      hyperforin, previously thought to be unique to Hypericum perforatum L. Together
      these results provide new insights into the biochemical complexity of an
      important medicinal species and demonstrate the power of in vitro manipulation in
      combination with untargeted metabolomic screening for the production of new
      germplasm.

PMID- 15449018
TI  - Powdery mildew pathogens can suppress the chitinase gene expression induced in
      detached inner epidermis of barley coleoptile.
AB  - Two-step PCR (RT-PCR and nested PCR) was used to detect gene expression in
      powdery mildew pathogen-infected cells of detached inner epidermis of barley
      coleoptiles. Cellular contents of infected cells were microscopically suctioned
      with a micropipette and subjected to PCR. Triosephosphate isomerase and
      glyceraldehyde-3-phosphate dehydrogenase genes involved in the glycolytic pathway
      and a stimulus-induced endochitinase gene were targeted, and their expression was
      determined by detecting cDNAs derived from spliced transcripts. The two gycolysis
      related genes were constantly expressed in the tissue irrespective of pathogen
      inoculation. In contrast, chitinase gene expression was induced in non-infected
      inner epidermis after detachment. After inoculation, this expression was
      selectively suppressed in pathogen-invaded cells, in spite of continuous
      expression in non-invaded cells of the same epidermis. Thus, the present method
      enabled us to directly analyze transcripts in individual cells at the infection
      site and assess the capability of the pathogen to regulate host gene expression.

PMID- 15449019
TI  - Flow cytometric analysis of protein content in Taxus protoplasts and single cells
      as compared to aggregated suspension cultures.
AB  - Plant suspension cultures are highly aggregated, preventing the direct
      application of flow cytometry for the study of population dynamics. The utility
      of single cells to accurately represent aggregated suspension cultures was tested
      through the analysis of total protein content. Specifically, protein content of
      two Taxus cuspidata suspension culture lines was studied using the Bradford assay
      for aggregated suspension cultures, and flow cytometry with fluorescein
      isothiocyanate staining for protoplasts and single cells. Taxus protein levels
      were measured at 75-160 mg per gram dry weight via the Bradford assay. Aggregated
      suspension cultures, protoplasts, and single cells predicted the same trend of
      protein content over the culture period (21 days). Normalized protein content of
      isolated single cells was statistically equivalent to aggregated suspensions for
      both cell lines. However, normalized protein content of isolated protoplasts
      showed significant differences from aggregated suspensions for one of the two
      cell lines. Elicitation with methyl jasmonate (MJ) is commonly utilized to
      increase paclitaxel accumulation in suspension cultures, and therefore the effect
      of MJ elicitation on protein content in aggregated suspensions, isolated single
      cells and protoplasts was assessed. Aggregated suspension cultures, protoplasts,
      and single cells did not show any change in total protein content following
      elicitation with MJ at 200 microM on day 7. This study illustrates the usefulness
      of flow cytometry for obtaining culture population information and the value of
      using intact single cells for the study of plant metabolism.

PMID- 15449020
TI  - Non-coordinate expression of peroxisome biogenesis, beta-oxidation and glyoxylate
      cycle genes in mature Arabidopsis plants.
AB  - The expression of three genes that encode proteins involved in peroxisome
      biogenesis, beta-oxidation and the glyoxylate cycle was studied in Arabidopsis
      plants by fusing their promoter regions to the reporter gene luciferase. Malate
      synthase showed an extremely restricted pattern of expression, being detected
      only in young seedlings and the root tips of older plants. PEX1 and 3-ketoacyl
      thiolase (PED1) were expressed in roots, mature leaves, stems and flowers.
      However, only thiolase was up-regulated by starvation. Immunoblotting confirmed
      that neither malate synthase nor the other unique glyoxylate cycle enzyme
      isocitrate lyase are expressed in senescent leaves. These results indicate that,
      in contrast to cucumber, pumpkin and barley, the glyoxylate cycle does not play a
      role in the recycling of carbon from the turnover of membrane lipids during
      senescence and starvation in Arabidopsis.

PMID- 15449021
TI  - Cold acclimation induced genes of trifoliate orange (Poncirus trifoliata).
AB  - Commercial citrus varieties are sensitive to low temperature. Poncirus trifoliata
      is a close relative of Citrus species and has been widely used as a cold-hardy
      rootstock for citrus production in low-temperature environments. mRNA
      differential display-reverse transcription (DDRT)-PCR and quantitative relative
      RT-PCR were used to study gene expression of P. trifoliata under a gradual cold
      acclimation temperature regime. Eight up-regulated cDNA fragments were isolated
      and sequenced. These fragments showed high similarities at the amino acid level
      to the following genes with known functions: betaine/proline transporter, water
      channel protein, aldo-keto reductase, early light-induced protein, nitrate
      transporter, tetratricopeptide-repeat protein, F-box protein, and ribosomal
      protein L15. These cold-acclimation up-regulated genes in P. trifoliata are also
      regulated by osmotic and photo-oxidative signals in other plants.

PMID- 15449022
TI  - HLA-DRB1 and -DQB1 alleles and gene polymorphisms of selected cytokines in
      systemic lupus erythematosus.
AB  - OBJECTIVE: The objective of this study was to evaluate the genetic profiles of
      selected cytokines (transforming growth factor beta 1, tumor necrosis factor
      alpha, interleukin-6, interferon gamma, and interleukin-10) in systemic lupus
      erythematosus and the contributions of human leukocyte antigen (HLA)-DRB1 and 
      DQB1 alleles to susceptibility for this disease. PATIENTS AND METHODS: The study
      was carried out in 24 SLE patients and 36 healthy controls (from Upper Silesia)
      using polymerase chain reaction methods. All persons were of Caucasoid origin.
      Standard association analysis was used to compare the HLA alleles and frequency
      of cytokine gene polymorphisms between these groups. RESULTS: Only the frequency
      of HLA-DRB1*07 allele was higher in SLE patients than controls (odds ratio 2.92,
      95% confidence interval 1.16-7.33), but the difference did not reach statistical
      significance when Bonferroni's adjustment procedure was performed. No other
      significant associations were noted between class II alleles (DR1-DR6, DR8-DR10,
      DQ1-DQ4) and SLE. The frequency of the interleukin-6 GG and GC genotypes was
      significantly higher in SLE patients than in controls, and a significantly higher
      percentage of the G vs C alleles between patients and controls was revealed (odds
      ratio 2.53, 95% confidence interval 1.37-4.65, chi-squared test 8.16, P < 0.05).
      The most significant association of increased frequency of the G allele with SLE
      was more commonly noted in HLA-DRB1*07-positive patients (odds ratio 10.29, 95%
      confidence interval 5.34-19.83, P < 0.001). These data indicate that this
      combination could contribute toward determining the susceptibility to SLE, but
      its possible significance will require confirmation by further studies.

PMID- 15449023
TI  - Pedobarography and its relation to radiologic erosion scores in rheumatoid
      arthritis.
AB  - OBJECTIVE: The aim of this study was to assess probable plantar pressure
      alterations in rheumatoid arthritis (RA) patients by comparison with normal
      subjects and to investigate the probable relation between pressure distribution
      under the foot and radiologic foot erosion score. METHODS: Two hundred feet of 50
      chronic RA patients and 50 healthy controls were evaluated. Static and dynamic
      pedobarographic evaluations were used to define the plantar pressure
      distribution. Also, the modified Larsen scoring system was used to detect the
      staging of erosions on feet radiograms of the RA patients. RESULTS: Static
      pedobarography revealed higher pressure and contact areas in the forefoot. All
      dynamic pedobarographic parameters except for plantar contact area were
      significantly different between the RA patients and control subjects. Patients
      with high erosion scores had higher static forefoot and dynamic phalanx peak
      pressure values. CONCLUSION: Pedobarographic investigation can be useful to
      evaluate pressure distribution disorders in RA feet and may provide suitable
      guidelines for the design of various plantar supports.

PMID- 15449024
TI  - Metastatic vertebral tumor misdiagnosed in magnetic resonance imaging as benign
      degenerative bone marrow changes: a case report.
AB  - Many disorders including congenital, degenerative, inflammatory, and neoplastic
      lesions are associated with low back pain. It is essential to differentiate
      between malignant disease and the more common causes of back pain. We report a
      man with low back and right groin pain as a result of metastatic breast carcinoma
      which was misdiagnosed in magnetic resonance imaging as benign degenerative
      changes.

PMID- 15449025
TI  - Selective serotonin reuptake inhibitors in familial Mediterranean fever: are we
      treating depression or inflammation?

PMID- 15449026
TI  - [Therapy-induced tumor regression in adult soft tissue sarcomas-morphological
      findings].
AB  - Morphological findings of 21 soft tissue sarcomas of adulthood following
      preoperative chemo- and/or radiotherapy including perfusion therapy and resection
      are presented. The therapy-induced changes included a spectrum ranging from total
      tumor regression up to still completely vital tumor (median of all cases: 30%
      vital tumor tissue). 7 of 21 sarcomas (33%) were evaluated as responders (grade I
      III). So-called malignant fibrous histiocytoma (MFH) revealed a good tumor
      response to preoperatively administered therapy (regression grades I and II).
      Myxoid/round-cell liposarcoma exhibited regression grades of IV-V (i.e. 30% up to
      95% vital tumor tissue, non-responders). Synovial sarcoma was characterized by
      regression grades III up to VI (i.e. up to 100% vital tumor tissue without any
      signs of regression, 83% non-responders). Completely vital tumor was evident in 2
      synovial sarcomas despite preoperative tumor therapy. These findings hint towards
      differences in response of distinct sarcoma entities to preoperative chemo
      /radiotherapy. A grading of therapy-induced tumor regression in adult soft tissue
      sarcomas may best refer to already established grading schemes (e.g. according to
      the grading scheme for osteosarcomas following chemotherapy of Salzer-Kuntschik).
      A report of sarcoma resection specimens should include the percentage of vital
      tumor tissue.

PMID- 15449029
TI  - Hepatitis B reactivation in a patient receiving radiolabeled rituximab.

PMID- 15449030
TI  - Protein C system defects in Indian children with thrombosis.
AB  - As ethnic variations are known to exist in inherited genetic defects, the clinico
      haematological profile of Indian children with thrombophilia may be different
      from that of Caucasians. The aim of the study was to analyse the phenotypic and
      genotypic causes of thrombophilia in Indian children. Forty patients with
      arterial (21 patients) and venous (19 patients) thrombosis were the subjects of
      the study. Their age ranged from 6 days to 15 years. All of the patients were
      initially screened by Pro C Global assay. Activated protein C resistance (APCR)
      was measured. In cases with low Pro C Global values, protein C (PC), protein S
      (PS) and factor V G1691A, prothrombin G20210A and MTHFR C677T polymorphism were
      tested in all 40 cases. Of the 21 patients with arterial thrombosis, 4 (19%) had
      PC deficiency, 7 (33.3%) had PS deficiency and 1 (4.8%) had combined deficiency
      of PC and PS. Of the 19 patients with venous thrombosis, 5 (26.3%) each had PC
      and PS deficiency and 4 (21%) had combined PC and PS deficiency. Heterozygous
      factor V G1691A defect was seen in one (4.8%) patient with arterial thrombosis
      and three (15.8%) patients with venous thrombosis. Heterozygous MTHFR C677T
      polymorphism was seen in five (23.8%) patients with arterial thrombosis and in
      four (21%) patients with venous thrombosis. Prothrombin G20210A polymorphism was
      absent in all patients and controls. Protein C system defect is common in Indian
      children with thrombosis.

PMID- 15449031
TI  - Tricuspid regurgitation in patients with beta-thalassemia major.
AB  - Although cardiac complications remain the main causes of death in thalassemic
      patients, right heart dysfunction has been little studied and the mechanism is
      still unclear. Echocardiography was performed in 39 patients with beta
      thalassemia major and 35 aged-matched controls. The gender, age, heart rate,
      blood pressure, left ventricular ejection fraction (LVEF), acceleration time
      (AcT) of right ventricular outflow and right ventricular ejection time (RVET),
      AcT/RVET, and the presence of tricuspid regurgitation (TR) were compared between
      the two groups. We also compared the gender, age, age at first blood transfusion,
      serum ferritin level, alanine aminotransferase (ALT), the presence of antibodies
      to hepatitis C virus, liver fibrosis, splenectomy, platelet counts, diabetes
      mellitus, arrhythmia, cardiomegaly, LVEF, AcT, RVET, AcT/RVET, and signal
      intensity ratio (SIR) of myocardial magnetic resonance imaging (MRI) between
      thalassemic patients with and without TR. The incidence of TR in thalassemic
      patients was significantly higher than that in the control group (30.8 vs 11.4%,
      p=0.03). The incidences of splenectomy (p=0.03), platelet counts (p=0.01), and
      SIR of myocardial MRI (p=0.03) in thalassemic patients with TR were significantly
      higher than in those without TR. The AcT was shorter and the AcT/RVET ratio was
      smaller, suggesting higher pulmonary pressure in the thalassemic patients with
      TR. Occurrence of TR in patients with beta-thalassemia major may be a consequence
      of cardiac iron deposit, thrombocytosis, splenectomy, or pulmonary hypertension.

PMID- 15449032
TI  - Immunopathogenesis of acute graft-versus-host disease: implications for novel
      preventive and therapeutic strategies.
AB  - Acute graft-versus-host disease (GVHD) is a primary T-cell-mediated complication
      of allogeneic hematopoietic stem cell transplantation (HSCT), occurring when
      donor-derived T cells are stimulated by host antigen-presenting cells (APCs),
      enhanced by proinflammatory cytokines such as interleukin (IL)-1, IL-6, IL-8, and
      tumor necrosis factor (TNF)-alpha. Recent data indicate that besides differences
      in major histocompatibility and minor histocompatibility antigens, cytokine gene
      polymorphisms have a predictive value for the complication of GVHD. Patients with
      a high anti-inflammatory IL-10 production have been demonstrated to be protected
      from GVHD while patients with high TNF-alpha serum levels were more at risk for
      GVHD. Pharmacological immunosuppression for GVHD prophylaxis and therapy,
      including unspecific approaches with corticosteroids or methotrexate (MTX), as
      well as more specific therapy with cyclosporin A (CsA), tacrolimus (FK506),
      sirolimus, mycophenolate mofetil (MMF), antithymocyte globulin (ATG), and
      monoclonal antibodies (MAbs) directed against CD3, CD25, CD52, cytotoxic T
      lymphocyte antigen (CTLA)-4, CD40 ligand, or TNF-alpha, have been proven to be
      effective. Recent data on novel techniques to selectively deplete alloreactive T
      cells by removal, destruction, or anergy induction while preserving leukemia
      specific T-cell clones suggest a clinical benefit from these approaches. Gene
      modified T cells that can selectively be depleted and CD4(+)CD25(+) regulatory T
      cells are under investigation for their ability to modulate alloreactivity after
      HSCT. With a better understanding of the immunopathogenesis of acute GVHD and the
      technical improvement of recently described therapeutic approaches, such as
      removal of naive T cells, selection of Th2 cells, suicide gene transduced T
      cells, and adoptive transfer of regulatory T cells, the use of alloreactivity as
      a treatment modality may be expanded to nonhematological disease entities such as
      solid tumors or autoimmune disorders.

PMID- 15449033
TI  - Complete regression of primary gastric plasmacytoma following Helicobacter pylori
      eradication.

PMID- 15449035
TI  - Phase I/II study of immunotherapy with T-cell peptide epitopes in patients with
      stage IV melanoma.
AB  - Previous studies in small groups of patients suggested that immunization of
      melanoma patients with peptide epitopes recognized by T cells could induce
      regression of melanoma. This approach was tested in 36 patients with stage IV
      melanoma. The (MHC class I-restricted) peptides were from gp100, MART-1,
      tyrosinase, and MAGE-3. The gp100 and MART-1 peptides had been modified to
      increase their immunogenicity. In half the patients (groups 3 and 4) the peptides
      were given in the adjuvant Montanide-ISA-720, and half the patients in both
      groups were given GM-CSF s.c. for 4 days following each injection. Treatment was
      well tolerated except for two severe erythematous responses to Montanide-ISA-720
      and marked inflammatory responses at sites of GM-CSF administration in three
      patients. There were no objective clinical responses but stabilization of disease
      for periods from 3 to 12 months were seen in seven patients. Five of these were
      patients given the peptides in Montanide-ISA-720. Delayed-type hypersensitivity
      (DTH) skin test responses were also seen mainly in the patients given the
      peptides in Montanide-ISA-720. GM-CSF did not increase DTH responses in patients
      in the latter group but may have increased DTH responses in those not given
      peptides in Montanide-ISA-720. Inflammatory responses around s.c. metastases or
      regional lymph nodes were observed in two patients. These results suggest that
      the peptides are more effective when given in the adjuvant Montanide-ISA-720.
      Nevertheless, results from this study, together with those from a number of
      comparable studies, indicate that peptide vaccines are currently of minimal
      benefit to patients and support the need for ongoing development of new
      strategies in treatment of this disease.

PMID- 15449036
TI  - Preoperative mannan-binding lectin pathway and prognosis in colorectal cancer.
AB  - PURPOSE: Deficiency of the mannan-binding lectin (MBL) pathway of innate immunity
      is associated with increased susceptibility to infections. In patients with
      colorectal cancer (CRC), postoperative infection is associated with poor
      prognosis. The aim of the present study was to evaluate (1) the relation between
      the MBL pathway and postoperative infectious complications and survival of
      patients resected for CRC, and (2) the role of MBL in acute phase response
      compared to C-reactive protein (CRP). METHODS: Preoperative MBL concentration,
      MBL-associated serine protease (MBL/MASP) activity and CRP were determined in
      serum from 611 patients and 150 healthy controls. The patients were observed for
      8 years. Postoperative infections, recurrence and survival were recorded.
      RESULTS: The MBL pathway components were increased in the patients compared with
      the healthy controls (p < 0.0001). Low MBL levels were predictive of pneumonia (p
      = 0.01), and pneumonia (n = 87) was associated with poor survival (p = 0.003; HR
      = 1.5; 95% CI, 1.1 to 1.9). MBL and MBL/MASP activity showed no correlation with
      CRP (Spearman's rho = 0.02; 95% CI, -0.06 to 0.10). CONCLUSION: Low preoperative
      MBL levels are predictive of pneumonia, which is associated with poorer survival.
      MBL concentration and MBL/MASP activity was not predictive of other postoperative
      infections or long-term prognosis, and showed no correlation with CRP.

PMID- 15449037
TI  - Peptide immunisation of HLA-DR-transgenic mice permits the identification of a
      novel HLA-DRbeta1*0101- and HLA-DRbeta1*0401-restricted epitope from p53.
AB  - Because of the central role of CD4(+) T cells in antitumour immunity, the
      identification of the MHC class II-restricted peptides to which CD4(+) T cells
      respond has become a priority of tumour immunologists. Here, we describe a
      strategy permitting us to rapidly determine the immunogenicity of candidate HLA
      DR-restricted peptides using peptide immunisation of HLA-DR-transgenic mice,
      followed by assessment of the response in vitro. This strategy was successfully
      applied to the reported haemaglutinin influenza peptide HA(307-319), and then
      extended to three candidate HLA-DR-restricted p53 peptides predicted by the
      evidence-based algorithm SYFPEITHI to bind to HLA-DRbeta1*0101 (HLA-DR1) and HLA
      DRbeta1*0401 (HLA-DR4) molecules. One of these peptides, p53(108-122),
      consistently induced responses in HLA-DR1- and in HLA-DR4-transgenic mice.
      Moreover, this peptide was naturally processed by dendritic cells (DCs), and
      induced specific proliferation in the splenocytes of mice immunised with p53
      cDNA, demonstrating that immune responses could be naturally mounted to the
      peptide. Furthermore, p53(108-122) peptide was also immunogenic in HLA-DR1 and
      HLA-DR4 healthy donors. Thus, the use of this transgenic model permitted the
      identification of a novel HLA-DR-restricted epitope from p53 and constitutes an
      attractive approach for the rapid identification of novel immunogenic MHC class
      II-restricted peptides from tumour antigens, which can ultimately be incorporated
      in immunotherapeutic protocols.

PMID- 15449038
TI  - Rituximab induces different but overlapping sets of genes in human B-lymphoma
      cell lines.
AB  - The therapeutic unconjugated anti-CD20 Mab rituximab is used for the treatment of
      B-non-Hodgkin's lymphomas. We have studied the direct biological effects,
      signalling and gene expression profiles induced by rituximab in two human B
      lymphoma cell lines, DHL4 and BJAB, using microarray, quantitative PCR and gel
      shift analysis. Rituximab alone inhibited thymidine uptake and induced homotypic
      adhesion in DHL4 only, but not BJAB. Analysis of Affymetrix microchips carrying
      probes for about 10,000 human cDNAs, allowed us to identify 16 genes in DHL4 and
      12 in BJAB induced by rituximab at 4 h. Eleven and seven of these genes were
      specific for DHL4 and BJAB, respectively; whereas the remaining five were up
      regulated in both cell lines. Mean induction ranged from 2- to 16-fold. Real time
      PCR analysis allowed us to confirm up-regulation of all genes identified, except
      one in BJAB. Time course of induction of eight genes was studied, showing peak
      induction in most cases at 4 h. The up-regulation of 5/5 genes was also observed
      with the F(ab')(2) fragment of rituximab. Analysis of three further B-cell
      lymphoma lines showed that gene induction is not restricted to BJAB and DHL4.
      Finally, we show that rituximab alone can induce AP1 activation in both cell
      lines and provide evidence that the ERK1/2 pathway is involved in the rituximab
      mediated up-regulation of gene expression. These data demonstrate that rituximab
      alone has direct signalling capacity in different B-lymphoma lines, inducing
      distinct but overlapping sets of genes which may play a role in the biological
      and/or therapeutic effect of the antibody.

PMID- 15449039
TI  - Expression of MHC class I, MHC class II, and cancer germline antigens in
      neuroblastoma.
AB  - BACKGROUND: Neuroblastoma is the most common solid extracranial tumor in
      childhood, still with poor survival rates for metastatic disease. Neuroblastoma
      cells are of neuroectodermal origin and express a number of cancer germline (CG)
      antigens. These CG antigens may represent a potential target for immunotherapy
      such as peptide-based vaccination strategies. OBJECTIVE: The purpose of this
      study was to analyze the presence of MAGE-A1, MAGE-A3/A6, and NY-ESO-1 on an mRNA
      and protein level and to determine the expression of MHC class I and MHC class II
      antigens within the same tumor specimens. METHODS: A total of 68 tumors were
      available for RT-PCR, and 19/68 tumors were available for immunohistochemical
      (IHC) analysis of MAGE-A1, MAGE-A3/A6, and NY-ESO-1. In parallel, the same tumors
      were stained with a panel of antibodies for MHC class I and MHC class II
      molecules. RESULTS: Screening of 68 tumor specimens by RT-PCR revealed expression
      of MAGE-A1 in 44%, MAGE-A3/A6 in 21%, and NY-ESO-1 in 28% of cases.
      Immunohistochemistry for CG antigens of selected tumors showed good agreement
      between protein and gene expression. However, staining revealed a heterogeneous
      expression of CG antigens. None of the selected tumors showed MHC class I or MHC
      class II expression. CONCLUSIONS: mRNA expression of MAGE-A1, MAGE-A3/A6, and NY
      ESO-1 is congruent with the protein expression as determined by
      immunohistochemistry. The heterogeneous CG-antigen expression and the lack of MHC
      class I and II molecules may have implications for T-cell-mediated immunotherapy
      in neuroblastoma.

PMID- 15449040
TI  - Distribution of labelled anti-tenascin antibodies and fragments after injection
      into intact or partly resected C6-gliomas in rats.
AB  - INTRODUCTION: For treatment of malignant glioma, radioimmunotherapy has become a
      valuable alternative for more than 2 decades. Surprisingly, very little is known
      about the distribution of intralesionally administered labelled antibodies or
      fragments. We investigated the migration of labelled antibodies and antibody
      fragments injected into intact and partly resected C6-glioma in rats at different
      times after injection. MATERIALS AND METHODS: Nine days after induction of a C6
      glioma, 5 microl of 125I-labelled murine anti-tenascin antibodies (n = 31) or
      125I-labelled fragments of anti-tenascin antibodies (n = 32) was injected slowly
      into the tumour (group I). In group II the tumour was subtotally resected 9 days
      after induction of the C6-glioma, and 24 h later the labelled antibodies (n = 30)
      or fragments (n = 12) were injected into the resection cavity. At 6, 24 or 48 h
      after the injection, animals were sacrificed, and brains removed. Distribution of
      labelled antibodies and fragments was determined by superimposing autoradiographs
      onto frozen sections and HE-stained neighbouring sections using a digital image
      analysing system. RESULTS: After injection into intact C6-glioma, labelled
      antibodies covered a maximum distance of 3.2 +/- 1.0, 4.1 +/- 1.9 and 4.8 +/- 0.9
      mm after 6, 24 and 48 h, respectively; while labelled fragments were found at a
      distance of 6.7 mm (+/-1.1) after 24 h and 5.8 mm (+/-0.9) after 48 h
      (significant in univariate analysis). Following partial tumour resection, the
      respective distances at 24 h were 3 +/- 0.4 mm for anti-tenascin antibodies and
      3.4 +/- 0.3 mm for Fab fragments. CONCLUSION: After injection into C6-glioma,
      labelled fragments are able to cover a greater distance than labelled antibodies.
      Injection of antibodies and fragments 1 day after tumour resection results in
      reduced velocity of both antibodies and fragments.

PMID- 15449041
TI  - Phenotype and function of human natural killer cells purified by using a clinical
      scale immunomagnetic method.
AB  - Infection, disease relapse, graft failure, and graft-versus-host disease (GVHD)
      are significant adverse events associated with allogeneic bone marrow
      transplantation. Donor natural killer (NK) cells may be an ideal cell type for
      prevention or treatment of all these adverse events. Therefore, we investigated
      the phenotype and function of human NK cells purified by using a clinical-scale
      immunomagnetic method. We found that the NK cell purification procedures did not
      adversely affect the expression of killer cell immunoglobulin-like receptors,
      adhesion molecules, intracellular cytokines, perforin, and granzyme B. Purified
      NK cells had extensive proliferative capacity and potent antitumor activity when
      assessed using an immunodeficient mouse model. While all mice transplanted with
      unpurified mononuclear cells developed GVHD, none of the mice transplanted with
      purified NK cells did. NK cells were highly susceptible to lysis by antithymocyte
      globulin (ATG), whereas G-CSF had a minimal effect on their natural cytotoxicity.
      These results support future clinical investigation of the use of purified NK
      cells for adoptive immunotherapy in the absence of ATG.

PMID- 15449042
TI  - Immunotherapy with bovine aortic endothelial cells in subcutaneous and
      intracerebral glioma models in rats: effects on survival time, tumor growth, and
      tumor neovascularization.
AB  - High-grade gliomas are aggressive tumors of the central nervous system
      characterized by endothelial cell proliferation and a high degree of vascularity.
      Conventional antitumoral treatments (i.e., surgery, radiotherapy, and
      chemotherapy) do not achieve satisfactory results (median survival in
      glioblastoma 12-18 months). It has been suggested that immunotherapy with
      xenogenic endothelial cells could slow tumor growth rate in a number of tumors in
      a murine model, but the study did not include gliomas. In experiments performed
      in our laboratory, vaccination with proliferating bovine aortic endothelium
      increased survival time in Fischer rats inoculated intracerebrally with 9L.
      Immunotherapy was also able to reduce the growth of subcutaneously injected 9L
      gliosarcoma cells in Fischer rats and to decrease microvessel density within the
      tumors, in the absence of major organ toxicity. Immunoglobulins (Ig) in the sera
      from vaccinated rats stained bovine aortic endothelium as well as human umbilical
      vein endothelium in active proliferation. Moreover, immune sera from immunized
      rats stained microvessels of human malignant glioma specimens and vessels of
      intracerebrally implanted tumors. Two proteins of MW of 11 and 19 kDa were
      identified by Western blot as targets of Ig elicited by vaccination. A possible
      future development is to select peptides/proteins suitable for vaccination in
      humans, avoiding the biohazards connected with xenogenic whole-cell vaccination.

PMID- 15449043
TI  - Immunohistochemical characterisation of the monoclonal antibody BLCA-38 for the
      detection of prostate cancer.
AB  - BACKGROUND: Monoclonal antibodies (MAbs) can be used to detect, image and treat
      cancers. This study aimed to characterise the binding of BLCA-38 MAbs to human
      prostate cancer cell lines, human prostate cancer biopsy samples and normal
      tissues to enable future targeted studies. METHODS: BLCA-38 antigen expression on
      cancer lines was determined by flow cytometry; that on patient specimens from
      normal tissues and cancers was tested by immunohistochemistry using fresh frozen
      tissues or paraffin-embedded tissues that had undergone antigen retrieval.
      RESULTS: Cell surface BLCA-38 antigen expression was seen on DU-145, PC-3, PC-3 M
      and PC-3 M-MM2 prostate cancer lines, but LNCaP, MDA PCa 2a or MDA PCa 2b lines
      were negative. Other human lines, including 8/12 bladder cancer and A431 vulval
      epidermoid cells, but not breast cancer lines, expressed BLCA-38 antigen.
      Staining occurred in glandular epithelial cells in the majority of frozen, and
      paraffin-embedded prostate cancer tissues and was occasionally seen in prostatic
      intraepithelial neoplasia (PIN). No staining was observed in normal cadaver
      tissues or in benign areas from various other cancer tissues. CONCLUSIONS: The
      BLCA-38 antibody binds to the majority of human prostate cancers but not to
      normal cells, and has potential for targeting novel therapies in patients with
      this disease.

PMID- 15449044
TI  - Lower percentages of monocytes with CD80, CD86 and HLA-DR molecule expression in
      pediatric cancer.

PMID- 15449045
TI  - Heart abscess revealed by nuclear medicine imaging.

PMID- 15449046
TI  - Sequential 123I-iododexetimide scans in temporal lobe epilepsy: comparison with
      neuroimaging scans (MR imaging and 18F-FDG PET imaging).
AB  - PURPOSE: Muscarinic acetylcholine receptors (mAChRs) play an important role in
      the generation of seizures. Single-photon emission computed tomography (SPECT)
      with 12I-iododexetimide (IDEX) depicts tracer uptake by mAChRs. Our aims were to:
      (a) determine the optimum time for interictal IDEX SPECT imaging; (b) determine
      the accuracy of IDEX scans in the localisation of seizure foci when compared with
      video EEG and MR imaging in patients with temporal lobe epilepsy (TLE); (c)
      characterise the distribution of IDEX binding in the temporal lobes and (d)
      compare IDEX SPECT and 18F-fluorodeoxyglucose (FDG) positron emission tomography
      (PET) in identifying seizure foci. METHODS: We performed sequential scans using
      IDEX SPECT imaging at 0, 3, 6 and 24 h in 12 consecutive patients with refractory
      TLE undergoing assessment for epilepsy surgery. Visual and region of interest
      analyses of the mesial, lateral and polar regions of the temporal lobes were used
      to compare IDEX SPECT, FDG PET and MR imaging in seizure onset localisation.
      RESULTS: The 6-h IDEX scan (92%; kappa=0.83, p=0.003) was superior to the 0-h
      (36%; kappa=0.01, p>0.05), 3-h (55%; kappa=0.13, p>0.05) and 24-h IDEX scans in
      identifying the temporal lobe of seizure origin. The 6-h IDEX scan correctly
      predicted the temporal lobe of seizure origin in two patients who required
      intracranial EEG recordings to define the seizure onset. Reduced ligand binding
      was most marked at the temporal pole and mesial temporal structures. IDEX SPECT
      was superior to interictal FDG PET (75%; kappa=0.66, p=0.023) in seizure onset
      localisation. MR imaging was non-localising in two patients in whom it was normal
      and in another patient in whom there was bilateral symmetrical hippocampal
      atrophy. CONCLUSION: The 6-h IDEX SPECT scan is a viable alternative to FDG PET
      imaging in seizure onset localisation in TLE.

PMID- 15449047
TI  - Evidence of increased chromosomal abnormalities in French Polynesian thyroid
      cancer patients.
AB  - PURPOSE: The aim of this study was to evaluate the frequency of chromosomal
      abnormalities in thyroid cancer patients before and after radioactive iodine
      administration in order to assess cytogenetic particularity in Polynesian thyroid
      cancer patients. METHODS: Chromosomal abnormalities were studied in 30 Polynesian
      patients with differentiated thyroid cancer, prior to and 4 days after 131I
      administration. Unstable chromosomal abnormalities were counted in peripheral
      blood lymphocytes using a conventional cytogenetic method. Peripheral blood was
      irradiated in vitro at different doses (0.5, 1 and 2 Gy) in order to establish
      the dose-response of the lymphocytes. Control groups were composed of 50 European
      thyroid cancer patients before and after first administration of 131I, and of ten
      European healthy donors. In addition, in vitro irradiation assays were performed
      at different doses (0.5, 1 and 2 Gy). RESULTS: The relative risk of spontaneous
      dicentrics before any radiation treatment was 2.9 (95% CI 1.7-5.1) times higher
      among Polynesian thyroid patients than among European thyroid cancer patients.
      After in vitro irradiation, the rise in frequency of dicentrics was similar in
      the Polynesian thyroid cancer group and the European thyroid patients and healthy
      donors. Four days after administration of 3.7 GBq 131I, the relative risk for a
      dicentric per cell was 1.3 (95% CI 1.0-1.5) times higher in Polynesian than in
      European patients. This can be explained by higher 131I retention in Polynesian
      compared with European patients. The results obtained revealed an increased
      frequency of cytogenetic abnormalities in Polynesian thyroid cancer patients
      compared with European control patients. CONCLUSION: These preliminary findings
      are compatible with possible previous environmental aggression and therefore
      imply a need for further investigations on larger series including, in
      particular, French Polynesian healthy donors. In addition to French Polynesians,
      Maori and Hawaiian control groups could be useful.

PMID- 15449048
TI  - Involvement of pulmonary endothelial cell injury in the pathogenesis of pulmonary
      fibrosis: clinical assessment by 123I-MIBG lung scintigraphy.
AB  - PURPOSE: Pulmonary microvascular endothelial injury may be involved in the
      pathogenesis of pulmonary fibrosis (PF). The aim of this study was to evaluate
      the pulmonary vascular status in patients with PF by lung scintigraphic
      assessment of 123I-metaiodobenzylguanidine (123I-MIBG), which reflects latent
      endothelial cell lesions. METHODS: We assessed lung 123I-MIBG kinetics and
      clinical indices in 23 PF patients and 16 controls. Mean uptake ratios of lung to
      mediastinum (L/M) were calculated in anterior planar images at 30 (early image)
      and 270 (delayed image) min after intravenous injection of 123I-MIBG. The
      pulmonary mean washout rate (WR) of 123I-MIBG was also calculated. RESULTS: The
      L/M ratio in early images, but not in delayed images, was significantly lower in
      the PF patients than in the controls (L/M(early) 1.41+/-0.14 vs 1.53+/-0.10,
      p<0.01; L/M(delayed) 1.28+/-0.10 vs 1.33+/-0.07, p=NS). WR was significantly
      reduced in the PF patients compared with the controls (28.6%+/-3.1% vs 34.2%+/
      5.1%, p<0.001). In the study subjects (PF patients plus controls) there were
      significant relationships between lung WR of (123)I-MIBG and other diagnostic
      parameters for the severity of PF, such as vital capacity (r=0.625, p<0.0001),
      total lung capacity (r=0.691, p<0.0001), carbon monoxide diffusing capacity
      (r=0.622, p<0.0001), serum angiotensin-converting enzyme activity (r=0.422,
      p<0.01), carbohydrate antigen KL-6 levels (r=-0.495, p<0.01) and surfactant
      protein-D levels (r=-0.461, p<0.01). When control subjects were excluded, similar
      significant correlations were observed between WR and %TLC (r=0.508, p<0.05),
      DL(CO) (r=0.593, p<0.01) and serum ACE activity (r=0.515, p<0.05) in the PF
      patients. CONCLUSION: These results suggest that endothelial cell injury plays a
      significant role in the pathogenesis of PF, and that lung WR of 123I-MIBG, which
      is a specific marker of endothelial damage, can serve as a novel diagnostic tool
      to evaluate the functional severity of PF.

PMID- 15449049
TI  - In vitro detection of mdr1 mRNA in murine leukemia cells with 111In-labeled
      oligonucleotide.
AB  - PURPOSE: The feasibility of intracellular mdr1 mRNA expression detection with
      radiolabeled antisense oligonucleotide (ODN) was investigated in the murine
      leukemia cell line, P388/S, and its subclonal, adriamycin-resistant cell line,
      P388/R. METHODS: The expression level of mdr1 mRNA was analyzed by reverse
      transcription-polymerase chain reaction (RT-PCR). Existence of the multidrug
      resistance (MDR) phenomenon was assessed via cellular uptake of 99mTc-sestamibi
      (MIBI), a known substrate for P-glycoprotein. A 15-mer phosphorothioate antisense
      ODN complementary to the sequences located at -1 to 14 of mdr1 mRNA and its
      corresponding sense ODN were conjugated with the cyclic anhydride of diethylene
      triamine penta-acetic acid (cDTPA) via an amino group linked to the terminal
      phosphate at the 5' end at pH 8-9. The DTPA-ODN complexes at concentrations of
      0.1-17.4 microM were reacted with 111InCl3 at pH 5 for 1 h. The hybridization
      affinity of labeled ODN was evaluated with size-exclusion high-performance liquid
      chromatography following incubation with the complementary sequence. Cellular
      uptake of labeled ODN was examined in vitro. Furthermore, enhancing effects of
      synthetic lipid carriers (Transfast) on transmembrane delivery of ODN were
      assessed. RESULTS: P388/R cells displayed intense mdr1 mRNA expression in
      comparison with P388/S cells. 99mTc-MIBI uptake in P388/S cells was higher than
      that in P388/R cells. Specific radioactivity up to 1,634 MBq/nmol was achieved
      via elevation of added radioactivity relative to ODN molar amount. The
      hybridization affinity of antisense 111In-ODN was preserved at approximately 85%
      irrespective of specific activity. Cellular uptake of antisense 111In-ODN did not
      differ from that of sense 111In-ODN in either P388/S cells or P388/R cells.
      However, lipid carrier incorporation significantly increased transmembrane
      delivery of 111In-ODN; moreover, specific uptake of antisense 111In-ODN was
      demonstrated in P388/R cells. CONCLUSION: Radiolabeling of ODN at high specific
      radioactivity and specific uptake of antisense 111In-ODN in drug-resistant cells
      may facilitate future gene imaging of mdr1 mRNA.

PMID- 15449050
TI  - Electrocardiographic-gated dual-isotope simultaneous acquisition SPECT using 18F
      FDG and 99mTc-sestamibi to assess myocardial viability and function in a single
      study.
AB  - PURPOSE: Dual-isotope simultaneous acquisition single-photon emission computed
      tomography (DISA SPECT) with 18F-fluorodeoxyglucose (FDG) and (99m)Tc-sestamibi
      appears attractive for the detection of viable myocardium because it permits
      simultaneous assessment of glucose utilisation and perfusion. Another potential
      benefit of this approach is that the measurement of left ventricular (LV)
      function may be possible by ECG gating. The aim of this study was to test the
      hypothesis that both myocardial viability and LV function can be assessed by a
      single ECG-gated 18F-FDG/(99m)Tc-sestamibi DISA SPECT study, based on comparison
      with 18F-FDG/13N-ammonia positron emission tomography (PET) and magnetic
      resonance imaging (MRI) as reference techniques. METHODS: Thirty-three patients
      with prior myocardial infarction underwent ECG-gated 18F-FDG/(99m)Tc-sestamibi
      DISA SPECT and 18F-FDG/13N-ammonia PET on a single day. Of these, 25 patients
      also underwent cine-MRI to assess LV function. The LV myocardium was divided into
      nine regions, and each region was classified as viable or scar using a
      semiquantitative visual scoring system as well as quantitative analysis. The
      global and regional LV function measured by gated SPECT was compared with the
      results of MRI. RESULTS: There was good agreement in respect of viability (90
      96%, kappa 0.74-0.85) between DISA SPECT and PET by either visual or quantitative
      analysis. Furthermore, although both global and regional LV function measured by
      gated SPECT agreed with those by MRI, (99m)Tc-sestamibi showed a closer
      correlation with MRI than did 18F-FDG. CONCLUSION: In conclusion, ECG-gated DISA
      SPECT provides information on myocardial viability, as well as global and
      regional LV function, similar to that obtained by PET and MRI.

PMID- 15449052
TI  - Differential gene expression in stromal cells of human giant cell tumor of bone.
AB  - Giant cell tumor (GCT) offers a unique model for the hematopoietic-stromal cell
      interaction in human bone marrow. Evidence has been presented that GCT stromal
      cells (GCTSCs) promote accumulation, size and activity of the giant cells.
      Although GCTSCs are considered the neoplastic component of GCT, little is known
      about their genetic basis and, to date, a tumor-specific gene expression pattern
      has not been characterized. Mesenchymal stem cells (MSCs) have been identified as
      the origin of the GCT neoplastic stromal cell. Using state of the art array
      technology, expression profiling was applied to enriched stromal cell populations
      from five different GCTs and two primary MSCs as controls. Of the 29
      differentially expressed genes found, 25 showed an increased expression.
      Differential mRNA expression was verified by real-time polymerase chain reaction
      analysis of 10 selected genes, supporting the validity of cDNA arrays as a tool
      to identify tumor-related genes in GCTSCs. Increased expression of two oncogenes,
      JUN and NME2, was substantiated at the protein level, utilizing
      immunohistochemical evaluation of GCT sections and Western-blot analysis.
      Increased phosphorylation of JUN Ser-63 was also found.

PMID- 15449053
TI  - Synchronous granulomatous cholecystitis and fibroelastosis of the gallbladder.
AB  - We describe an unusual form of xanthogranulomatous cholecystitis in a 69-year-old
      man, with abundant intramural concrement formation and a local fibroelastosis of
      the adjacent interstitium and arteries. The gallbladder was obtained following
      resection of an adenocarcinoma of the gastro-esophageal junction without evidence
      of metastases. Only two cases of fibroelastosis of the gallbladder have
      previously been reported, and its pathogenesis is unknown. The influence of bile
      that leaked into the interstitium or a specific local tissue response to
      cytokines secreted by histiocytes are among the possible explanations for its
      development in our case.

PMID- 15449054
TI  - Influence of age on adenomatous polyposis coli and p53 mutation frequency in
      sporadic colorectal cancer-rarity of co-occurrence of mutations in APC, K-ras,
      and p53 genes.
AB  - INTRODUCTION: Previous studies have investigated the possibility that specific
      mutations may be related to specific clinicopathological features. However, most
      previous investigations included only an average age (40-80 years) group of
      sporadic colorectal cancers and, moreover, studied only a single gene in
      isolation. Therefore, the influence of age on these mutation frequencies remains
      unclear, despite age being considered a risk factor for genetic mutation.
      MATERIALS AND METHODS: This study included 122 sporadic colorectal cancers from
      three different age groups and analyzed mutation frequencies of adenomatous
      polyposis coli (APC), K-ras, and p53 genes and microsatellite instability to
      determine their mutation frequencies and relationships with clinicopathological
      features. RESULTS: Significantly lower p53 mutation frequencies were observed
      among young (32 years old or younger) and old (86 years old or older) patient
      groups compared with an average age (39-85 years old) patient group (14.3% and
      19.2% versus 51.5%, P<0.001). APC mutation frequency (11.8%) was significantly
      lower in highly aggressive (Dukes' stage D) tumors ( P=0.003) than in the other
      stage tumors (Dukes' stage A, B, and C). Additionally, simultaneous occurrence of
      all three genetic alterations in an individual tumor was rare (below 5%).
      Statistical analysis further confirmed that mutation number in Dukes' D tumors
      occurred less frequently than expected in other stage tumors ( P=0.008).
      CONCLUSIONS: Genetic alterations of sporadic colorectal cancers have different
      relationships with age or tumor stage. Additionally, most sporadic colorectal
      tumors do not necessarily require following the widely accepted genetic model,
      because the three key genetic mutations, APC, K-ras, and p53, rarely occur
      simultaneously.

PMID- 15449055
TI  - Wing venation and Distal-less expression in Heliconius butterfly wing pattern
      development.
AB  - Here we show that major color pattern elements of Heliconius butterfly wings
      develop independently of wing venation. We recovered a hybrid Heliconius
      displaying a mutant phenotype with a severe vein deficiency. Although this
      butterfly lacked most of its wing veins, the large, melanic banding patterns
      typical of the genus were conserved across the entire wing. The only obvious
      correlation between vein reduction and pigment patterns was a loss of vein
      associated melanin stripes near the distal margin of the wings. We examined the
      expression of the eyespot-associated transcription factor Distal-less in a banded
      and a spotted species of Heliconius and found no obvious relationship between
      protein expression and the band or spot patterns typical of the genus. Together,
      our results suggest that the melanic bands and spots in Heliconius are unlikely
      to be derived from an eyespot determination system. We propose that major
      elements of Heliconius wing pattern formation are based primarily on a complex,
      whole-wing proximodistal axis system.

PMID- 15449056
TI  - Characterization of photosynthetic electron transport in bundle sheath cells of
      maize. I. Ascorbate effectively stimulates cyclic electron flow around PSI.
AB  - Redox changes of the reaction-center chlorophyll of photosystem I (P700) and
      chlorophyll fluorescence yield were measured in bundle sheath strands (BSS)
      isolated from maize (Zea mays L.) leaves. Oxidation of P700 in BSS by actinic
      light was suppressed by nigericin, indicating the generation of a proton gradient
      across the thylakoid membranes of BSS chloroplasts. Methyl viologen, which
      transfers electrons from photosystem I (PSI) to O2, caused a considerable
      decrease in the reduction rate of P700+ in BSS after turning off actinic light,
      showing that electron flow from the acceptor side of PSI to stromal components is
      critical for this reduction. Ascorbate (Asc), and to a lesser extent malate
      (Mal), caused a lower level of P700+ in BSS under aerobic conditions in far-red
      light, implying electron donation from these substances to the intersystem
      carriers. When Asc or Mal was added to BSS during pre-illumination under
      anaerobic conditions in the presence of 3-(3,4-dichlorophenyl)-1,1-dimethyl urea
      (DCMU), the far-red-induced level of P700+ was lowered. The results suggest Asc
      and Mal can cause reduction of stromal donors, which in turn establishes
      conditions for rapid PSI-driven P700+ reduction. Addition of these metabolites
      also strongly stimulated the development of a proton gradient in thylakoids under
      aerobic conditions in the absence of DCMU, i.e. under conditions analogous to
      those in vivo. Ascorbate was a much more effective electron donor than Mal,
      suggesting it has a physiological role in activation of cyclic electron flow
      around PSI.

PMID- 15449057
TI  - Pectin and the role of the physical properties of the cell wall in pollen tube
      growth of Solanum chacoense.
AB  - The cell wall is one of the structural key players regulating pollen tube growth,
      since plant cell expansion depends on an interplay between intracellular driving
      forces and the controlled yielding of the cell wall. Pectin is the main cell wall
      component at the growing pollen tube apex. We therefore assessed its role in
      pollen tube growth and cytomechanics using the enzymes pectinase and pectin
      methyl esterase (PME). Pectinase activity was able to stimulate pollen
      germination and tube growth at moderate concentrations whereas higher
      concentrations caused apical swelling or bursting in Solanum chacoense Bitt.
      pollen tubes. This is consistent with a modification of the physical properties
      of the cell wall affecting its extensibility and thus the growth rate, as well as
      its capacity to withstand turgor. To prove that the enzyme-induced effects were
      due to the altered cell wall mechanics, we subjected pollen tubes to micro
      indentation experiments. We observed that cellular stiffness was reduced and
      visco-elasticity increased in the presence of pectinase. These are the first
      mechanical data that confirm the influence of the amount of pectins in the pollen
      tube cell wall on the physical parameters characterizing overall cellular
      architecture. Cytomechanical data were also obtained to analyze the role of the
      degree of pectin methyl-esterification, which is known to exhibit a gradient
      along the pollen tube axis. This feature has frequently been suggested to result
      in a gradient of the physical properties characterizing the cell wall and our
      data provide, for the first time, mechanical support for this concept. The
      gradient in cell wall composition from apical esterified to distal de-esterified
      pectins seems to be correlated with an increase in the degree of cell wall
      rigidity and a decrease of visco-elasticity. Our mechanical approach provides new
      insights concerning the mechanics of pollen tube growth and the architecture of
      living plant cells.

PMID- 15449058
TI  - SUMO conjugation in plants.
AB  - Covalent attachment of small proteins to substrates can regulate protein activity
      in eukaryotes. SUMO, the small ubiquitin-related modifier, can be covalently
      linked to a broad spectrum of substrates. An understanding of SUMO's role in
      plant biology is still in its infancy. In this review, we briefly summarize the
      enzymology of SUMO conjugation (sumoylation), and the current knowledge of SUMO
      modification in Arabidopsis thaliana (L.) Heynh. and other plants, in comparison
      to animals and fungi. Furthermore, we assemble a list of potential pathway
      components in the genome of A. thaliana that have either been functionally
      defined, or are suggested by similarity to pathway components from other
      organisms.

PMID- 15449059
TI  - Time-lapse tracking of barley androgenesis reveals position-determined cell death
      within pro-embryos.
AB  - Following abiotic stress to induce barley (Hordeum vulgare L.) androgenesis, the
      development of 794 enlarged microspores in culture was monitored by time-lapse
      tracking. In total, 11% of the microspores tracked developed into embryo-like
      structures (type-I pathway), 36% formed multicellular structures (type-II
      pathway) and 53% of the microspores followed gametophytic divisions, accumulated
      starch and died in the first days of tracking (type-III pathway). Despite the
      microspore fate, enlarged microspores showed similar morphologies directly after
      stress treatment. Ultrastructural analysis, however, revealed two morphologically
      distinct cell types. Cells with a thin intine layer and an undifferentiated
      cytoplasm after stress treatment were associated with type-I and type-II
      pathways, whereas the presence of differentiated amyloplasts and a thick intine
      layer were associated with the type-III pathway. Tracking revealed that the first
      morphological change associated with embryogenic potential was a star-like
      morphology, which was a transitory stage between uninucleate vacuolated
      microspores after stress and the initiation of cell division. The difference
      between type-I and type-II pathways was observed during the time they displayed
      the star-like morphology. During the transition phase, embryo-like structures in
      the type-I pathway were always released out of the exine wall at the opposite
      side of the pollen germ pore, whereas in the type-II pathway multicellular
      structures were unable to break the exine and to release embryo-like structures.
      Moreover, by combining viability studies with cell tracking, we show that release
      of embryo-like structures was preceded by a decrease in viability of the cells
      positioned at the site of exine wall rupture. These cells were also positively
      stained by Sytox orange, a cell death indicator. Thereby, we demonstrate, for the
      first time, that a position-determined cell death process marks the transition
      from a multicellular structure into an embryo-like structure during barley
      androgenesis.

PMID- 15449060
TI  - Molecular and biochemical characterization of the Capsicum annuum calcium
      dependent protein kinase 3 (CaCDPK3) gene induced by abiotic and biotic stresses.
AB  - The isolated full-length Capsicum annuum calcium-dependent protein kinase 3
      (CaCDPK3) cDNA clone was selected from the chili pepper expressed sequence tag
      database (http://www.pdrc.re.kr/ks200201/pepper.html). Phylogenetic analysis
      based on the deduced amino acid sequence of CaCDPK3 cDNA revealed significant
      sequence similarity to the winter squash (Cucurbita maxima) CmCPK2 gene (81%
      identity). Genomic gel blot analysis disclosed that CaCDPK3 belongs to a
      multigene family in the pepper genome. CaCDPK3 expression was root tissue
      specific, as shown by Northern blot data. The gene was rapidly induced in
      response to various osmotic stress factors and exogenous abscisic acid
      application in pepper leaves. Moreover, CaCDPK3 RNA expression was induced by an
      incompatible pathogen and by plant defense-related chemicals such as ethephon,
      salicylic acid and jasmonic acid. The biochemical properties of CaCDPK3 were
      investigated using a CaCDPK3 and glutathione S-transferase (GST) fusion protein.
      The recombinant proteins retained calcium-binding ability, and displayed
      autophosphorylation activity in vitro in a calcium-dependent manner. Further
      transient-expression studies showed that CaCDPK3 fused with soluble modified
      green fluorescent protein (smGFP) localized to the cytosol in chili pepper
      protoplasts. We propose that CaCDPK3 is implicated in biotic and abiotic stresses
      in pepper plants.

PMID- 15449061
TI  - Two isoforms of the A subunit of the vacuolar H(+)-ATPase in Lycopersicon
      esculentum: highly similar proteins but divergent patterns of tissue
      localization.
AB  - The plant vacuolar H(+)-translocating ATPase (V-ATPase, EC 3.6.1.34) generates a
      H+ electro-chemical gradient across the tonoplast membrane. We isolated two full
      length cDNA clones (VHA-A1 and VHA-A2) from tomato (Lycopersicon esculentum Mill.
      cv. Large Cherry Red) coding for two isoforms of the V-ATPase catalytic subunit
      (V-ATPases A1 and A2). The cDNA clones encoding the two isoforms share 90%
      identity at the nucleotide level and 96% identity at the amino acid level. The 5'
      and 3'-untranslated regions, however, are highly diverse. Both V-ATPase A1 and
      A2 isoforms encode polypeptides of 623 amino acids, with calculated molecular
      masses of 68,570 and 68,715, respectively. The expression of VHA-A1 and
      accumulation of V-ATPase A1 polypeptide were ubiquitous in all tissues examined.
      In response to salinity, the abundances of both transcript (VHA-A1) and protein
      (V-ATPase A1) of the A1 isoform in leaves were nearly doubled. In contrast to the
      A1 isoform, VHA-A2 transcript and V-ATPase A2 polypeptide were only detected in
      abundance in roots, and in minor quantities in mature fruit. In roots,
      accumulation of transcripts and polypeptides did not change in response to
      salinity for either isoform. Subcellular localization indicated that the highest
      levels of both V-ATPase A1 and A2 isoforms were in the tonoplast. However,
      significant quantities of both isoforms were detected in membranes associated
      with endoplasmic reticulum and/or Golgi. Immunoprecipitation of dissociated V1
      domains using isoform-specific antibodies showed that V1 domains consist of
      either V-ATPase A1 or A2 catalytic subunit isoforms.

PMID- 15449062
TI  - La3+ uptake and its effect on the cytoskeleton in root protoplasts of Zea mays L.
AB  - La(3+) ions are known to antagonize Ca(2+) and are used as a Ca(2+) channel
      blocker but little is known on the direct effects of La(3+). Micromolar La(3+)
      concentrations promoted root growth while higher concentrations were inhibitory.
      The uptake of La(3+) in maize root protoplasts revealed a membrane binding
      component (0.14 and 0.44 pmol min(-1) protoplast(-1) for 100 and 1,000 microM
      La(3+)) followed by a slower concentration and time-dependent uptake. Uptake was
      reduced by Ca(2+), but had no substantial effect on other ions. La(3+) shifted
      microtubule organization from random to parallel but caused aggregation of
      microfilaments. Our data suggest that La(3+) is taken up into plant cells and
      affects growth via stabilization of the cytoskeleton.

PMID- 15449063
TI  - Antisense inhibition of sorbitol synthesis leads to up-regulation of starch
      synthesis without altering CO2 assimilation in apple leaves.
AB  - Sorbitol is a primary end-product of photosynthesis in apple (Malus domestica
      Borkh.) and many other tree fruit species of the Rosaceae family. Sorbitol
      synthesis shares a common hexose phosphate pool with sucrose synthesis in the
      cytosol. In this study, 'Greensleeves' apple was transformed with a cDNA encoding
      aldose 6-phosphate reductase (A6PR, EC 1.1.1.200) in the antisense orientation.
      Antisense expression of A6PR decreased A6PR activity in mature leaves to
      approximately 15-30% of the untransformed control. The antisense plants had lower
      concentrations of sorbitol but higher concentrations of sucrose and starch in
      mature leaves at both dusk and predawn. (14)CO(2) pulse-chase labeling at ambient
      CO(2) demonstrated that partitioning of the newly fixed carbon to starch was
      significantly increased, whereas that to sucrose remained unchanged in the
      antisense lines with decreased sorbitol synthesis. Total activities of ribulose
      1,5-bisphosphate carboxylase/oxygenase (EC 4.1.1.39), sucrose-phosphate synthase
      (EC 2.4.1.14), and ADP-glucose pyrophosphorylase (EC 2.7.7.27) were not
      significantly altered in the antisense lines, whereas both stromal and cytosolic
      fructose-1,6-bisphosphatase (EC 3.1.3.11) activities were higher in the antisense
      lines with 15% of the control A6PR activity. Concentrations of glucose 6
      phosphate and fructose 6-phosphate (F6P) were higher in the antisense plants than
      in the control, but the 3-phosphoglycerate concentration was lower in the
      antisense plants with 15% of the control A6PR activity. Fructose 2, 6
      bisphosphate concentration increased in the antisense plants, but not to the
      extent expected from the increase in F6P, comparing sucrose-synthesizing species.
      There was no significant difference in CO(2) assimilation in response to photon
      flux density or intercellular CO(2) concentration. We concluded that cytosolic
      FBPase activity in vivo was down-regulated and starch synthesis was up-regulated
      in response to decreased sorbitol synthesis. As a result, CO(2) assimilation in
      source leaves was sustained at both ambient CO(2) and saturating CO(2).

PMID- 15449064
TI  - Standards of medical treatment and nutrition in Crohn's disease.
AB  - Crohn's disease is a condition of chronic inflammation potentially involving any
      location of the alimentary tract from mouth to anus but with a propensity for the
      distal small bowel and proximal large bowel. Frequent complications include
      stricture and fistula. Numerous extra-intestinal manifestations may also be
      present. The aetiology of Crohn's disease is incompletely understood, and
      therapy, although generally effective in alleviating the symptoms, is not
      curative. Due to the heterogeneity of the disease a major need for the
      therapeutic approach is the ability to define subgroups with distinct
      characteristics. However, with regard to the heterogeneity of demographic,
      anatomic and disease behaviour characteristics, distillation of the numerous
      possible phenotypes in simple categories is a formidable task. In the present
      review the focus will be on clinically relevant situations providing therapeutic
      algorithms according to international guidelines.

PMID- 15449065
TI  - Development of clinical celiac disease after pancreatoduodenectomy: a potential
      complication of major upper abdominal surgery.
AB  - BACKGROUND: Celiac disease is a gluten-induced disease of global malabsorption.
      There is a subset of patients with celiac disease who are free of major symptoms
      but who have typical damage to the intestinal mucosa (silent disease). We present
      the case of a 50-year-old white woman with no clinical symptoms of celiac disease
      who developed diarrhea and weight loss 12 weeks after a pancreatoduodenectomy for
      ampullary cancer. METHODS: Microbiological and biochemical examination of the
      feces did not provide clues useful to diagnosis, and diarrhea was not affected by
      pancreatic enzyme replacement or administration of antiperistaltic drugs.
      RESULTS: Review of the pathologic specimen and blood tests were compatible with
      celiac disease. CONCLUSION: This clinical scenario illustrates that subclinical
      celiac disease may be an underdiagnosed cause of malabsorption after major upper
      gastrointestinal surgery and should be considered in the differential diagnosis
      of diarrhea after pancreatoduodenectomy.

PMID- 15449066
TI  - Dynamical simulation of speech cooperative articulation by muscle linkages.
AB  - Different kinds of articulators, such as the upper and lower lips, jaw, and
      tongue, are precisely coordinated in speech production. Based on a perturbation
      study of the production of a fricative consonant using the upper and lower lips,
      it has been suggested that increasing the stiffness in the muscle linkage between
      the upper lip and jaw is beneficial for maintaining the constriction area between
      the lips (Gomi et al. 2002). This hypothesis is crucial for examining the
      mechanism of speech motor control, that is, whether mechanical impedance is
      controlled for the speech motor coordination. To test this hypothesis, in the
      current study we performed a dynamical simulation of lip compensatory movements
      based on a muscle linkage model and then evaluated the performance of
      compensatory movements. The temporal pattern of stiffness of muscle linkage was
      obtained from the electromyogram (EMG) of the orbicularis oris superior (OOS)
      muscle by using the temporal transformation (second-order dynamics with time
      delay) from EMG to stiffness, whose parameters were experimentally determined.
      The dynamical simulation using stiffness estimated from empirical EMG
      successfully reproduced the temporal profile of the upper lip compensatory
      articulations. Moreover, the estimated stiffness variation significantly
      contributed to reproduce a functional modulation of the compensatory response.
      This result supports the idea that the mechanical impedance highly contributes to
      organizing coordination among the lips and jaw. The motor command would be
      programmed not only to generate movement in each articulator but also to regulate
      mechanical impedance among articulators for robust coordination of speech motor
      control.

PMID- 15449067
TI  - Integrated characterization of the human chemoreflex system controlling
      ventilation, using an equilibrium diagram.
AB  - The chemoreflex system controlling ventilation consists of two subsystems, i.e.,
      the central controller (controlling element), and peripheral plant (controlled
      element). We developed an integral framework to quantitatively characterize
      individual ventilatory regulation by experimental determination of an equilibrium
      diagram using a modified metabolic hyperbola and the CO2 response curve. In 13
      healthy males, the steady-state arterial CO2 pressure (P(a)CO2) and minute
      ventilation (V(E)) were measured. To characterize the central controller, we
      changed fraction of inspired CO2 (0, 3.5, 5 and 6% CO2 in 80% oxygen with
      nitrogen balance) and measured the P(a)CO2-V(E) relation. To characterize the
      peripheral plant, we altered V(E) by hyper- or hypoventilation using a visual
      feedback method, which made it possible to control both tidal volume and
      breathing frequency, and measured the VE-P(a)CO2 relation. The intersection
      between the two relationship lines gives the operating point. The relationship
      between P(a)CO2 and V(E) for the central controller was reasonably linear in each
      subject (r2 = 0.808-0.995). The peripheral plant approximated a modified
      metabolic hyperbolic curve (r = 0.962-0.996). The operating points of the system
      estimated from the two relationship lines were in good agreement with those
      measured under the closed-loop condition. The gain of the central controller was
      1.9 (1.0) l min(-1) mmHg(-1) and that of the peripheral plant was 3.0 (0.5) mmHg
      l(-1) min(-1). The total loop gain, the product of the two gains, was 5.3 (2.5).
      We conclude that human ventilatory regulation by the respiratory chemoreflex
      system can be quantitatively characterized using an equilibrium diagram. This
      framework should be useful for understanding the mechanisms responsible for
      abnormal ventilation under various pathophysiological conditions.

PMID- 15449069
TI  - Adenocarcinoma in situ coexisting with carcinoma in situ of the cervix during
      pregnancy.
AB  - CASE REPORT: We report a pregnant patient with adenocarcinoma in situ (AIS)
      coexisting with carcinoma in situ (CIS) of the cervix diagnosed by conization at
      16 weeks' gestation. Apoptotic activity was higher in the CIS lesion than in the
      AIS lesion in the cone biopsy specimen. Postpartum evaluation confirmed the
      disappearance of CIS lesion with positive cone margins, however, multifocal AIS
      with negative cone margins was found. CONCLUSION: Clinical course and biological
      features of AIS associated with pregnancy may be different from those of CIS.

PMID- 15449070
TI  - Acute abdomen as first symptom of acute leukemia.
AB  - CASE REPORT: The authors presented a rare case of acute abdomen syndrome caused
      by the rupture of the corpus rubrum as the first symptom in a 35-years-old woman
      with the acute lymphatic leukemia. During the laparotomy is notice diffuse
      bleeding from under skin blood vessels and muscles. The blood was
      electrocoagulated and was sewn with catgut sutures. The right ruptured corpus
      rubrum was found from which fresh blood was leaking. The right ovary was
      carefully resected and sutured, and each ligature was bleeding. At the beginning
      of the surgery laboratory analysis results arrived which showed a high
      leukocytosis (28.0 x 10(9)/l) with sever thrombocytopenia (10 x 10(9)/l) and
      afibrinogenemia (0.1 g/l) with anemia (1.9 x 10(12)/l erythrocyte, haematocrit
      0.24), which indicated leukemia with disseminated intravascular coagulopathy
      (antithrombin III levels 0.9 g/l, D-dimers 1989 micro g/l). RESULT. A year later
      she died with the picture of severe disseminated intravascular coagulopathy,
      agranulocytosis and septic condition with multiorganic failure.

PMID- 15449071
TI  - Vaginal angiomyofibroblastoma.
AB  - INTRODUCTION: Angiomyofibroblastoma (AMF) is a rare benign subcutaneous
      vulvovaginal tumour. The vaginal location of this tumour is very rare with only
      seven documented cases in literature. CASE REPORT: We report one case of AMF at
      this uncommon location.

PMID- 15449072
TI  - Cervical stump cancer: a study of 14 cases.
AB  - CASE REPORT: This is a report on 14 patients with cervical stump cancer, aged 30
      to 68 years old (median = 53 years), seen in a public university hospital. Over a
      15-year period, 363 cases of cervical cancer were treated, of which fourteen
      (3.85%) were in the cervical stump. The time interval between subtotal
      hysterectomy and the diagnosis of the neoplasm varied from 9 days to 27 years
      (median = 9.3 years). 28.6% of the patients were in stage I, 42.9% in stage II
      and 28.6% in stage III. Fibromyoma was the major reason for the subtotal
      hysterectomy. Three patients underwent Wertheim-Meigs surgery, 1 in association
      with radiotherapy, and the other 11 patients had radiotherapy alone. The survival
      ranged from 12 to 120 months (median = 53.3 months). CONCLUSION: Subtotal
      hysterectomy should be avoided whenever possible in populations with restricted
      access to screening programs for cancer of the uterine cervix.

PMID- 15449073
TI  - Splenosis presenting with adnexal mass: a case report.
AB  - CASE REPORT: A 21-year-old woman presenting with low abdominal discomfort,
      dysmenorrhoea and pelvic mass was misdiagnosed as endometriosis. She had post
      traumatic splenic rupture and laparotomy history. RESULTS. Pelvic splenosis was
      diagnosed at laparotomy. Pelvic mass was removed and the other implants were
      left.

PMID- 15449074
TI  - Serum TNF-alpha, IL-6, lupus anticoagulant and anticardiolipin antibody in women
      with and without a past history of recurrent miscarriage.
AB  - OBJECTIVE: The aim of the this study was to investigate Lupus Anticoagulan (LA),
      Anticardiolipin Antibody (ACA), Tumor Necrosis Factor-alpha (TNF-alpha) and
      Interleukin-6 (IL-6) serum levels in 40 pregnant and 20 nonpregnant. MATERIALS
      AND METHODS: The women were divided into three groups. The first group consisted
      of 20 pregnant women of less than 20 gestational weeks and a past history of
      habitual abortion . The second group consisted of 20 non pregnant patients with a
      past history of habitual abortion. The third group consisted of 20 healthy non
      pregnant women. RESULT: LA was found in only one patient in the Group 2. ACA Ig G
      positivity were found 1 patient in the Group 1, 3 patients Group 2 and 1 patient
      in Group 3. Mean ACA IgG was highest in the Group 2. High serum TNF-alpha levels
      were found in the 12 (60%), 6(30%) and 2 (10%) women in the Groups 1, 2, and 3,
      respectively. Significant difference were found for TNF-alpha among the groups
      (P<0.05). The highest level of TNF-alpha was found in the Group 1 and the lowest
      in the Group 3. There were statistically significant differences for IL-6 among
      the three groups (P>0.05). CONCLUSION: We propose that cytokines especially TNF
      alpha was found to be related to the pregnancy loss.

PMID- 15449075
TI  - Possible involvement of gelatinase A (MMP2) and gelatinase B (MMP9) in toxic
      epidermal necrolysis or Stevens-Johnson syndrome.
AB  - Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are
      considered to be drug-induced diseases, and are characterized by extensive
      mucocutaneous disorder and epidermal necrosis which result in the detachment of
      the epidermis. Inactive and active forms of metalloproteinases (MMP2 and MMP9)
      secreted by skin explants maintained in organ culture for 72 h and in blister
      fluid from two TEN and three SJS patients were investigated. Interestingly,
      lesional skin from both the TEN and the SJS patients cultured for 3 days in
      conditioned medium showed high levels of both 72 kDa progelatinase A and 66 kDa
      activated gelatinase A, and the 66 kDa activated form was not observed in
      cultures of skin from control individuals. Furthermore, indirect immunodetection
      showed the presence of MMP2 and MMP9 in TEN and SJS patients' skin. Increased
      gelatinase activity in the culture medium of TEN and SJS skin maintained in organ
      culture and in blister fluid indicates that these gelatinases may be responsible
      for the detachment of the epidermis in these drug-induced necrolyses.

PMID- 15449076
TI  - In situ expression of LAT (linker for activation of T cells) in pathological
      human skin with T-lymphoid infiltrate.
AB  - LAT is a 36-kDa transmembrane protein that plays an important role in linking
      engagement of the T-cell antigen receptor (TCR) to the biochemical events of T
      cell activation. It has been shown that LAT reacts with human T cells in normal
      and neoplastic lymphoid tissues, without restriction to any T cell subpopulation.
      This suggests that the expression of LAT in vivo may be a valuable addition to
      the panel of immunohistochemical markers used for immunostaining T cells. The
      expression of LAT has not yet been studied in human pathological skin conditions.
      We present our experience concerning LAT expression in both neoplastic and
      inflammatory dermatoses using an immunohistochemical approach on frozen sections
      from 42 patients. A variable reduction in LAT expression was observed in almost
      all the inflammatory and neoplastic skin conditions investigated, irrespective of
      the particular disease. Our study indicates that LAT(-) T cells are more common
      within the skin T-lymphoid infiltrate than was previously demonstrated in both
      normal and neoplastic lymphoid tissues. These findings suggest that, using a
      conventional immunoenzymatic approach on fresh frozen sections, LAT staining is
      an unreliable marker for the identification of T cells in human pathological skin
      conditions.

PMID- 15449077
TI  - Friction of ceramic and metal hip hemi-endoprostheses against cadaveric
      acetabula.
AB  - INTRODUCTION: Studies of hip arthroplasty have dealt mainly with total
      endoprosthesis, while tribology measurement values of hemi-endoprosthetic
      implants are rare. The small amount of experimental tribological data concerning
      materials of hemi-endoprosthetic implants in the form of pendulum trials, animal
      experiments, in vivo measurements on human hip joints and pin on disc studies
      report friction coefficients between 0.014 and 0.57; the friction coefficients
      measured in fresh human cadaver hip joints were determined between 0.001 and
      0.08. MATERIALS AND METHODS: The HEPFlEx-hip simulator was constructed to test
      the friction coefficients of unipolar femur head hemi-endoprostheses made of
      metal or ceramic against fresh cadaveric acetabula. Its plane of movement is
      uniaxial with a flexion-extension movement of +30/-18 degrees . The force is
      produced pneumatically dynamic with amounts of 2.5 kN. Newborn calf serum serves
      as a lubricant. We mounted 20 fresh porcine acetabula and 10 fresh human cadaver
      acetabula in the HEPFlEx-hip simulator and compared the two unipolar femur head
      hemi-endoprostheses (metal vs. ceramic). RESULTS: The mean friction coefficients
      against porcine acetabula were micro=0.017-0.082 for ceramic and micro=0.020
      0.101 for metal; against human cadaver acetabula micro=0.017-0.083 for ceramic
      and micro=0.019-0.118 for metal. The frictional coefficient deltas (metal
      ceramic) values of all measurements were Deltamicro=0.004 for porcine acetabula
      and Deltamicro=0.001 for cadaver acetabula. Box-plots graphics document
      significantly lower frictional coefficients of the ceramics. CONCLUSIONS: The
      lower frictional coefficients of ceramic compared to metal against fresh
      cadaveric acetabula may have a clinical impact on the process of the protrusion
      of the corresponding femoral head through the acetabulum.

PMID- 15449078
TI  - Development and validation of a colorectal functional outcome questionnaire.
AB  - BACKGROUND: After colorectal surgery, patients often experience impaired
      functional outcome. Faecal incontinence grading systems and self-assessment
      questionnaires are frequently used to assess these complaints. The available
      faecal incontinence grading systems have been validated, but have a limited
      focus, while more comprehensive questionnaires, which have been developed, have
      not been validated. AIMS: To investigate the reliability and validity of a newly
      developed, colorectal functional outcome (COREFO) questionnaire and of Dutch
      translations of the Hallbook questionnaire and an adapted version of the Vaizey
      questionnaire. PATIENT/METHODS: Two hundred fifty-seven patients with and without
      impaired functional outcome after (colorectal) surgery received a booklet
      containing the three questionnaires in random order by mail. One hundred seventy
      nine (70%) completed them, and 160 patients (90%) completed a retest within, on
      average, 18 days. RESULTS/FINDINGS: Reliability and validity were adequate for
      the COREFO and Hallbook questionnaire, with slight differences in the
      psychometric analyses in favour of the COREFO questionnaire. Significantly more
      patients found the COREFO questionnaire to reflect their problems best. The
      reliability of the Vaizey questionnaire was not sufficient.
      INTERPRETATION/CONCLUSIONS: The newly developed COREFO questionnaire and the
      previously unvalidated Hallbook questionnaire are both suitable instruments to
      evaluate functional outcome after colorectal surgery. The psychometric analyses
      showed a slight difference in favour of the COREFO questionnaire and
      significantly more patients preferred the COREFO questionnaire to the other
      questionnaires. Therefore, we prefer to use the COREFO questionnaire in future
      research.

PMID- 15449079
TI  - Perianal Paget's disease associated with rectal carcinoma: a rare report.

PMID- 15449080
TI  - Toldt's fascia flap: a new technique for repairing large diaphragmatic hernias.
AB  - The most popular techniques for repairing large diaphragmatic defects involve the
      use of synthetic patches. We present an alternative approach using living tissue.
      We reviewed our cases of congenital diaphragmatic hernia (CDH) diagnosed within
      the first 24 h of life from 1991 to 2003. Toldt's fascia (TF) flap was used to
      repair defects that were too large to repair primarily even though the anterior
      rim of the diaphragm was present. After confirming that a small medial muscle
      remnant of the diaphragm was present, its mesothelial covering was incised, and
      the incision was extended to the TF far enough to create a flap sufficiently
      large to repair the defect. The TF flap, consisting of the small medial muscle
      remnant, TF, peritoneum, and retroperitoneal connective tissue, was mobilized
      carefully from the ipsilateral kidney and adrenal gland, and the repair completed
      with interrupted sutures using nonabsorbable material. We used this TF flap
      approach in seven of 43 patients with CDH. Two had right-sided CDH. Six survived.
      The mean size of the diaphragmatic defects in the seven TF flap cases was 5.43+/
      0.53 x 3.86+/-1.07 cm, which was significantly larger than the defects in direct
      primary repair cases (3.40+/-0.77 x 2.03+/-0.59 cm) (p<0.01). The six survivors
      had good outcomes, and none of them have had recurrence of herniation or required
      any additional surgical intervention (mean follow-up period: 4.7 years). To the
      best of our knowledge, this is the first report of TF being used to repair large
      diaphragmatic hernias. Our technique is simple and has proven to be reliable for
      durable restoration of the diaphragm, suggesting that it could reduce the
      dependence on synthetic patch repair, which is associated with certain long-term
      complications.

PMID- 15449081
TI  - Surgical therapy for short bowel syndrome.
AB  - Patients with short bowel syndrome (SBS) suffer tremendous morbidity secondary to
      prolonged hospitalization and chronic parenteral nutrition (TPN). Overall, the
      majority of infants will adapt and ultimately become independent of TPN, but this
      process may require many months or years. Reasons for continued TPN dependency
      include bowel dysmotility, bacterial overgrowth, insufficient adaptation, or very
      short bowel length. It is this subpopulation of patients who may benefit from
      surgical procedures that optimize intestinal adaptation and increase the mucosal
      absorptive surface area. The goal of this review article is to summarize the
      process of intestinal adaptation and then to outline the surgical principles and
      techniques available to surgeons who treat this complicated group of patients.

PMID- 15449082
TI  - Pediatric tracheostomy: a 13-year experience.
AB  - Pediatric tracheostomy has been reported to be a surgical procedure with
      significant morbidity and mortality. The use of tracheostomy in airway management
      has changed over time as regards indication and outcome. A review of the last 13
      years' experience in our institution was carried out to focus on this group of
      patients and the recent trends in airway management. A retrospective analysis of
      hospital records was done and information collected with respect to age, gender,
      indication for tracheostomy, duration, complications, and follow-up. Thirty-nine
      tracheotomies were done in 36 patients, of whom males outnumbered females 2:1.
      The mean patient age was 41.6 months while nearly a third were newborns. The
      indications were congenital and acquired obstructive lesions. Apart from nine
      cases, all have been treated and decannulated. Follow-up ranged from 1 month to 8
      years, and decannulation time from 48 h to 45 months. Home tracheostomy care was
      very well managed by the parents. One tracheostomy-related death was encountered.
      Complications were minor and transient and occurred post-decannulation in our
      series, in contrast to the major complications, both acute and chronic, reported
      in the literature. More neonates and infants are undergoing tracheostomy and
      surviving. Pediatric tracheostomy is a safe procedure with home care by parents
      feasible.

PMID- 15449083
TI  - Nutritional state and herniorrhaphy in premature infants.
AB  - The incidence of inguinal hernia in premature infants is significantly high, and
      the optimal timing for its correction is controversial. Furthermore, whether the
      nutritional status of neonates will alter hernia diagnosis and postoperative
      results has not been demonstrated. The aim of this study was to analyze the
      results of premature neonates who underwent inguinal hernia repair before
      hospital discharge, comparing clinical features and perioperative data of two
      distinct nutritional groups. It was verified that early inguinal hernia repair is
      feasible without an escalation in the incidence of complications, thereby
      reducing the risk of incarceration and avoiding subsequent hospitalization.
      Moreover, premature infants had similar postoperative outcomes regardless of
      their nutritional status.

PMID- 15449084
TI  - A single institution observational study of early mechanical complications in
      central venous catheters (valved and open-ended) in children with cancer.
AB  - The use of indwelling central venous catheters (CVCs) has become essential for
      managing children undergoing cancer treatment. Various types of CVCs are
      available, but reports on complications observed in pediatric series are scarce.
      We describe our experience concerning early mechanical complications at our
      institute by providing a prospective evaluation of three types of CVCs that were
      inserted over a 39-month period. Between January 1, 2000, and March 31, 2003,
      double-lumen (DL) or single-lumen (SL) Hickman-Broviac (HB) and single-lumen
      pressure-activated safety-valved (PASV) catheters were inserted and prospectively
      evaluated. Five groups of possible mechanical complications were defined a
      priori: dislodgement, migration, rupture, accidental removal, and blockage. We
      took into consideration complications occurring only within the first 30 days of
      insertion. A total of 272 CVCs (118 PASV, 57 DL-HB, and 97 SL-HB) were inserted
      in 232 children. A total of 29 early mechanical complications (10.7% of all CVCs)
      were diagnosed: 15.2% of the PASV, 10.5% of the DL-HB, and 4.1% of the SL-HB.
      Elective removal of the catheter due to complications was required in eight
      patients. SL-HB catheters had fewer complications, while the complication rate
      and the number of devices that were removed were significantly higher in patients
      with PASV catheters. We conclude that catheter type correlates with the risk of
      early mechanical complications and removal.

PMID- 15449085
TI  - An unusual cause of acute abdomen: torsion of colonic duplication over a
      duplicated appendix.
AB  - A 2-year old boy with torsion of colonic duplication, which had a proximal
      communication with the cecum via an incomplete duplicated appendix, is presented.
      The clinical picture and complications of this rare association are discussed.

PMID- 15449086
TI  - Sensory innervation of normal and hypospadiac prepuce: possible implications in
      hypospadiology.
AB  - Sensory innervation of the skin influences wound healing through the release of
      neuropeptides from the nerve endings. The purpose of this study was to
      investigate the differences in the sensory innervation of the normal and the
      hypospadiac prepuce. The prepuce from 10 healthy children undergoing routine
      circumcision and 10 age-matched children undergoing hypospadias repair were
      submitted for immunohistochemistry, using antibodies against protein gene product
      (PGP) 9.5, calcitonin gene-related peptide (CGRP), and substance P (SP). The
      hypospadiac prepuce was found to be hypo-innervated for PGP 9.5 and CGRP positive
      nerves when compared with the normal prepuce ( p<0.05). The number of SP-positive
      nerves were increased in the hypospadiac prepuce, but not to statistical
      significance ( p=0.06, confidence interval >95%). There may be differences in the
      sensory innervation of the normal and hypospadiac prepuce. These differences in
      tissue environment may partly explain the postoperative edema, poor wound healing
      leading to urethrocutaneous fistula (UF), and increased analgesia requirements in
      patients undergoing hypospadias surgery.

PMID- 15449087
TI  - Omphalocele associated with a large multilobular umbilical cord pseudocyst.
AB  - The prevalence of umbilical cord cysts at 7-13 weeks' gestation is approximately
      3%. More than 20% of such cases are complicated by structural defects and/or
      chromosomal abnormalities such as trisomy 18. These cysts usually have a single
      cavity and are <5 cm in size. Therefore, when an umbilical cord cyst is detected
      in the 2nd trimester, the examination of fetal karyotype is recommended.
      Omphaloceles are also well known to be complicated by many anomalies, especially
      trisomy 18. We report a case of an omphalocele associated with a large
      multilobular umbilical pseudocyst (diameter >5 cm) in a patient with a normal
      karyotype, 46XY. These anomalies were diagnosed by fetal ultrasonography.
      However, the cyst was difficult to diagnose as an umbilical cord pseudocyst
      because it was very large and multilobulated. At 38.5 weeks of gestation, the
      patient was delivered by Cesarean section. The cyst was resected, and the
      omphalocele was closed by staged surgeries. Pathologic diagnosis of the cyst was
      the degeneration of Wharton's jelly. This diagnosis was made by the absence of
      epithelial lining inside the cyst wall, since the existence of epithelial cells
      correlates with true cysts.

PMID- 15449088
TI  - Bobble head doll syndrome in a child with a third ventricular cyst and
      hydrocephalus.
AB  - INTRODUCTION: The bobble head doll syndrome, mainly affecting children under 10
      years of age, is a rare and surgically treatable movement disorder characterized
      by head bobbing occurring at a rate of 2-3 times/s. Its pathophysiological
      mechanism is not well known but two main factors are commonly associated with the
      condition: a dilatation of the third ventricle and, more frequently, a cystic
      lesion rather than a solid mass in the region of the third ventricle.
      ILLUSTRATIVE CASE: The illustrative case concerns a child with a third
      ventricular cystic lesion and hydrocephalus who had experienced abnormal head
      movements since the age of 1 year as well as ataxia and tremor of the arms.
      Contrast cranial MRI, at the age of 3, demonstrated enlargement of the third and
      lateral ventricles, a ballooned cyst inside the third ventricle with compression
      of all the diencephalic structures, a funnel dilation of the cranial part of the
      aqueduct, and a cyst in the septum pellucidum. A ventriculoperitoneal shunt
      (Hakim-Cordis) was placed and the head bobbing, tremor of the arms, and ataxia
      disappeared immediately. CONCLUSION: The good and immediate clinical result in
      our case emphasizes the opinion that the reduction of CSF pressure is the best
      therapeutical option in the bobble head doll syndrome.

PMID- 15449089
TI  - Post-shunt ascites in infants with optic chiasmal hypothalamic astrocytoma: role
      of ventricular gallbladder shunt.
AB  - INTRODUCTION: We report a series of infants with optic chiasmal hypothalamic
      astrocytomas (OCHAs) who developed abdominal ascites following ventriculo
      peritoneal (VP) shunting. The mechanism of ascites development among these
      patients with OCHA remains speculative and unclear. METHODS: We treated four
      infants with hypothalamic tumors who were shunted for hydrocephalus using
      standard VP shunts and who subsequently experienced symptomatic ascites. RESULTS:
      In three patients the gallbladder proved an effective alternative site for
      shunting prior to conversion to other sites, and in one patient the gallbladder
      shunt remains functional and revision-free. CONCLUSIONS: Several aspects of the
      gallbladder as a reservoir for CSF make this approach appealing. Ventricular
      gallbladder shunting provided an effective (at least temporarily) receptacle for
      CSF in these patients.

PMID- 15449090
TI  - Ca2+, calmodulin and phospholipids regulate nitricoxide synthase activity in the
      rabbit submandibular gland.
AB  - Nitric oxide (NO) plays an important role as an intra- and intercellular
      signaling molecule in mammalian tissues. In the submandibular gland, NO has been
      suggested to be involved in the regulation of secretion and in blood flow. NO is
      produced by activation of NO synthase (NOS). Here, we have investigated the
      regulation of NOS activity in the rabbit submandibular gland. NOS activity was
      detected in both the cytosolic and membrane fractions. Characteristics of NOS in
      the cytosolic and partially purified membrane fractions, such as Km values for l
      arginine and EC(50) values for calmodulin and Ca(2+), were similar. A protein
      band that cross-reacted with anti-nNOS antibody was detected in both the
      cytosolic and membrane fractions. The membrane-fraction NOS activity increased
      1.82-fold with treatment of Triton X-100, but the cytosolic-fraction NOS activity
      did not. The NOS activity was inhibited by phosphatidic acid (PA) and
      phosphatidylinositol 4,5-bisphosphate (PIP(2)). The inhibitory effects of
      phospholipids on the NOS activity were relieved by an increase in Ca(2+)
      concentrations. These results suggest that the Ca(2+)- and calmodulin-regulating
      enzyme nNOS occurs in cytosolic and membrane fractions, and PA and PIP(2)
      regulate the NOS activity in the membrane site by regulating the effect of Ca(2+)
      in the rabbit submandibular gland.

PMID- 15449091
TI  - Symmetrical and asymmetrical gaits in the mouse: patterns to increase velocity.
AB  - The gaits of the adult SWISS mice during treadmill locomotion at velocities
      ranging from 15 to 85 cm s(-1) have been analysed using a high-speed video camera
      combined with cinefluoroscopic equipment. The sequences of locomotion were
      analysed to determine the various space and time parameters of limb kinematics.
      We found that velocity adjustments are accounted for differently by the stride
      frequency and the stride length if the animal showed a symmetrical or an
      asymmetrical gait. In symmetrical gaits, the increase of velocity is provided by
      an equal increase in the stride length and the stride frequency. In asymmetrical
      gaits, the increase in velocity is mainly assured by an increase in the stride
      frequency in velocities ranging from 15 to 29 cm s(-1). Above 68 cm s(-1),
      velocity increase is achieved by stride length increase. In velocities ranging
      from 29 to 68 cm s(-1), the contribution of both variables is equal as in
      symmetrical gaits. Both stance time and swing time shortening contributed to the
      increase of the stride frequency in both gaits, though with a major contribution
      from stance time decrease. The pattern of locomotion obtained in a normal mouse
      should be used as a template for studying locomotor control deficits after
      lesions or in different mutations affecting the nervous system.

PMID- 15449092
TI  - Functional differences in forebrain auditory regions during learned vocal
      recognition in songbirds.
AB  - Converging evidence implicates the auditory forebrain regions caudal medial
      mesopallium (formerly cmHV) and caudal medial nidopallium in the perceptual
      processing of conspecific vocalizations in songbirds. Little is known however,
      about more specific processing within these regions especially during song-based
      perceptual behaviors. One hallmark of the caudal medial mesopallium and caudal
      medial nidopallium, areas analogous to mammalian secondary auditory cortical
      structures, is their robust expression of the immediate-early-gene zenk in
      response to conspecific songs. Using European starlings operantly trained to
      recognize the songs of individual conspecifics, we show that the levels and
      patterns of zenk protein expression in the caudal medial nidopallium and caudal
      medial mesopallium differ when song recognition demands are placed on the system.
      In the caudal medial mesopallium, expression is significantly elevated above
      basal levels during the recognition of familiar songs, the acquisition of novel
      associations for familiar songs, and the acquisition of novel song
      discriminations. In the caudal medial nidopallium, however, expression is
      significantly elevated above basal levels only during the acquisition of novel
      song discriminations. The results directly implicate the caudal medial
      nidopallium and caudal medial mesopallium in at least a portion of the auditory
      processes underlying vocal recognition. Moreover, the observed differences
      between these regions imply the functional localization (or at least the
      concentration) of different auditory processing mechanisms within the caudal
      medial nidopallium and the caudal medial mesopallium.

PMID- 15449093
TI  - Spatial response properties of homing pigeon hippocampal neurons: correlations
      with goal locations, movement between goals, and environmental context in a
      radial-arm arena.
AB  - The amniote hippocampal formation plays an evolutionarily-conserved role in the
      neural representation of environmental space. However, species differences in
      spatial ecology nurture the expectation of species differences in how hippocampal
      neurons represent space. To determine the spatial response properties of homing
      pigeon ( Columba livia) HFneurons, we recorded from isolated units in birds
      freely navigating a radial arena in search of food present at four goal
      locations. Fifty of 76 neurons displayed firing rate variations that could be
      placed into three response categories. Location cells ( n=25) displayed higher
      firing rates at restricted locations in the arena space, often in proximity to
      goal locations. Path cells ( n=13) displayed higher firing rates as a pigeon
      moved between a subset of goal locations. Arena-off cells ( n=12) were more
      active when a pigeon was in a baseline holding space compared to inside the
      arena. Overall, reliability and coherence scores of the recorded neurons were
      lower compared to rat place cells. The differences in the spatial response
      profiles of pigeon hippocampal formation neurons, when compared to rats, provide
      a departure point for better understanding the relationship between spatial
      behavior and how hippocampal formation neurons participate in the representation
      of space.

PMID- 15449094
TI  - Disruption of masking by hypothalamic lesions in Syrian hamsters.
AB  - Negative masking of locomotor activity by light in nocturnal rodents is mediated
      by a non-image-forming irradiance-detection system in the retina. Structures
      receiving input from this system potentially contribute to the masking response.
      The suprachiasmatic nucleus (SCN) regulates locomotor activity and receives dense
      innervation from the irradiance-detection system via the retinohypothalamic
      tract, but its role in masking is unclear. We studied masking in adult Syrian
      hamsters (Mesocricetus auratus) with electrolytic lesions directed at the SCN.
      Hamsters were exposed to a 3.5:3.5 ultradian light/dark cycle and their wheel
      running activity was monitored. Intact hamsters showed robust masking, expressing
      less than 20% of their activity in the light even though light and dark occurred
      equally during their active times. In contrast, hamsters with lesions showed, on
      average, as much activity in the light as in the dark. Tracing of retinal
      projections using cholera toxin beta subunit showed that the lesions damaged
      retinal projections to the SCN and to the adjacent subparaventricular zone.
      Retinal innervation outside the hypothalamus was not obviously affected by the
      lesions. Our results indicate that retinohypothalamic projections, and the
      targets of these projections, to the SCN and/or adjacent hypothalamic areas play
      an important role in masking.

PMID- 15449095
TI  - [Neurodegeneration and neuroprotection].

PMID- 15449096
TI  - [Visual impairment in sudden retinal hemorrhage].

PMID- 15449097
TI  - [Transpupillary thermotherapy for subfoveal choroidal neovascularization. A 9
      month follow-up].
AB  - PURPOSE: The purpose of this study was to evaluate the efficiency, stability, and
      safety of transpupillary thermotherapy as a treatment of subfoveal occult
      choroidal neovascularizations (CNV) in age-related macular degeneration. METHODS:
      Transpupillary thermotherapy (TTT) was performed in 40 patients with uni- or
      bilateral predominantly occult CNV. Laser light derived from an infrared diode
      laser at 810 nm was used to apply spots for a duration of 60 s. A complete
      ophthalmic examination was performed prior to and 9 months after the treatment.
      RESULTS: After 9 months, visual acuity remained stable in 65% (+/-2 lines). In
      35% of the patients TTT could not prevent further visual loss. Retinal leakage,
      assessed by fluorescein angiography, stabilized in 67.5% of the treated patients.
      CONCLUSIONS: The present data show stabilization of visual acuity in 65% after
      TTT. Compared to the natural course of occult and mixed subfoveal CNV, these data
      give some evidence for patient benefit after TTT.

PMID- 15449099
TI  - Pneumococcal vaccination does not affect the genetic diversity of Moraxella
      catarrhalis isolates in children.

PMID- 15449100
TI  - Chimpanzees' (Pan troglodytes) use of gaze cues in object-choice tasks: different
      methods yield different results.
AB  - To assess the influence of different procedures on chimpanzees' performance in
      object-choice tasks, five adult chimpanzees were tested using three experimenter
      given cues to food location: gazing, glancing, and pointing. These cues were
      delivered to the subjects in an identical fashion but were deployed within the
      context of two distinct meta-procedures that have been previously employed with
      this species with conflicting results. In one procedure, the subjects entered the
      test unit and approached the experimenter (who had already established the cue)
      on each trial. In the other procedure, the subjects stayed in the test unit
      throughout a session, witnessed the hiding procedure, and waited for a delay of
      10 s during which the cue was provided. The subjects scored at high levels far
      exceeding chance in response to the gaze cue only when they approached the
      experimenter for each trial. They performed at chance levels when they stayed
      inside the test unit throughout the session. They scored at chance levels on all
      other cues irrespective of the procedure. These findings imply that (a)
      chimpanzees can immediately exploit social gaze cues, and (b) previous
      conflicting findings were likely due to the different meta-procedures that were
      used.

PMID- 15449101
TI  - The role of context specificity in learning: the effects of training context on
      explosives detection in dogs.
AB  - Various experiments revealed that if an animal learns a stimulus-response
      reinforcer relationship in one context and is then tested in another context
      there is usually a lessening of stimulus control, and the same discriminative
      stimuli that reliably controlled the behavior in the first context will have less
      effect in the new context. This reduction in performance is known as the "context
      shift effect." The effect of changing context on the probability of detecting
      explosives was investigated in seven highly trained explosives detection dogs
      (EDDs). In experiment 1 the dogs were trained alternately on path A, which always
      had five hidden explosives, and on a very similar path B, which never had any
      explosives. Within a few sessions the dogs showed a significant decrease in
      search behavior on path B, but not on path A. In experiment 2 the same dogs were
      trained only on path B with a target density of one explosive hidden every 4th
      day. The probability of the dogs now detecting the explosive was found to be
      significantly lower than in experiment 1. In experiment 3 the effect of the low
      target density as used in experiment 2 was investigated on a new but very similar
      path C. Both the detection probability for the one explosive every 4th day on the
      new path and the motivation to search were significantly higher than found in
      experiment 2. Finally, in experiment 4, an attempt was made to recondition the
      dogs to search on path B. Although trained for 12 daily sessions with one
      explosive hidden every session, the dogs failed to regain the normal levels of
      motivation they had shown on both new paths and on the paths that they knew
      usually contained explosives. The findings reveal that even a very intensively
      trained EDD will rapidly learn that a specific stretch of path does not contain
      explosives. The dog will then be less motivated to search and will miss newly
      placed targets. This learning is specific to the formerly always-clean path and
      is to some extent irreversible. However, the dog will search and detect normally
      on new paths even if they are very similar to the always-clean path. The data are
      discussed in terms of variables affecting renewal. The results suggest that
      following training designed to make a behavior "context independent," any
      extinction training will not generalize beyond that specific context used during
      the extinction training. In addition, if the behavior is extinguished in a
      specific context, it will be very difficult to restore that behavior in that
      context. These conclusions should be considered by anyone attempting to
      extinguish well-established trans-context behaviors.

PMID- 15449102
TI  - Tool-use learning in Tonkean macaques (Macaca tonkeana).
AB  - The transmission of tool use is a rare event in monkeys. Such an event arose in a
      group of semi-free-ranging Tonkean macaques (Macaca tonkeana) in which leaning a
      pole against the park's fence (branch leaning) appeared and spread to several
      males. This prompted us to test individual and social learning of this behavior
      in seven young males. In the first experiment, three males learned individually
      to obtain a food reward using a wooden pole as a climbing tool. They began using
      the pole to retrieve the reward only when they could alternatively experience
      acting on the object and reaching the target. In a second experiment, we first
      tested whether four other subjects could learn branch leaning after having
      observed a group-mate performing the task. Despite repeated opportunities to
      observe the demonstrator, they did not learn to use the pole as a tool. Hence we
      exposed the latter subjects to individual learning trials and they succeeded in
      the task. Tool use was not transmitted in the experimental situation, which
      contrasts with observations in the park. We can conclude that the subjects were
      not able to recognize the target as such. It is possible that they recognized it
      and learned the task individually when we alternated the opportunity to act upon
      the object and to reach the reward. This suggests that these macaques could then
      have associated the action they exercised upon the pole and the use of the pole
      as a means to reach the reward.

PMID- 15449103
TI  - Configural/holistic processing or differential element versus compound
      similarity.
AB  - Before accepting a configural or holistic account of visual perception, one
      should be sure that an analytic (elemental) account does not provide an equal or
      better explanation of the results. I suggest that when one forms a compound of a
      color and a line orientation with one element previously trained as an S+ and the
      other as an S-, the resulting transfer found will depend on the relative salience
      of the two elements, and most important, the similarity of the compound to each
      of the training stimuli. Thus, if a line orientation is placed on a colored
      background (a separable compound), it will appear more like the colored field
      used in training, and color will control responding. However, if the line itself
      is colored (an integral compound), the compound will appear more like the line
      used in training, and line orientation will control responding. Not only does
      this account do a better job of explaining the data but it is simpler and it is
      testable.

PMID- 15449104
TI  - Detour behaviour in three species of birds: quails (Coturnix sp.), herring gulls
      (Larus cachinnans) and canaries (Serinus canaria).
AB  - Detour behaviour is the ability of an animal to reach a goal stimulus by moving
      round any interposed obstacle. It has been widely studied and has been proposed
      as a test of insight learning in several species of mammals, but few data are
      available in birds. A comparative study in three species of birds, belonging to
      different eco-ethological niches, allows a better understanding of the cognitive
      mechanism of such detour behaviour. Young quails (Coturnix sp.), herring gulls
      (Larus cachinnans) and canaries (Serinus canaria), 1 month old, 10-25 days old
      and 4-6 months old, respectively, were tested in a detour situation requiring
      them to abandon a clear view of a biologically interesting object (their own
      reflection in a mirror) in order to approach that object. Birds were placed in a
      closed corridor, at one end of which was a barrier through which the object was
      visible. Four different types of barrier were used: vertical bar, horizontal bar,
      grid and transparent. Two symmetrical apertures placed midline in the corridor
      allowed the birds to adopt routes passing around the barrier. After entering the
      apertures, birds could turn either right or left to re-establish social contact
      with the object in the absence of any local sensory cues emanating from it.
      Quails appeared able to solve the task, though their performance depended on the
      type of barrier used, which appeared to modulate their relative interest in
      approaching the object or in exploring the surroundings. Young herring gulls also
      showed excellent abilities to locate spatially the out-of-view object, except
      when the transparent barrier was used. Canaries, on the other hand, appeared
      completely unable to solve the detour task, whatever barrier was in use. It is
      suggested that these species differences can be accounted for in terms of
      adaptation to a terrestrial or aerial environment.

PMID- 15449105
TI  - Immunoinflammatory responses and fibrogenesis.
AB  - In response to injury, tissues adjacent to the damaged area initiate a cascade of
      inflammatory and matrix remodeling events that are necessary to restore tissue
      integrity and function. The typical features of such healing effects in adult
      mammals are deposition of matrix proteins, which mature to scar tissues. In
      general, the wound healing response demonstrates certain commonalities across
      organs, but there are also organ-specific mechanisms. Such organ-specific
      controlled healing and uncontrolled tissue scarring are partly determined by the
      bioactivities of resident cells and local microenvironments, which are influenced
      by multiple factors, including the presence of specific types of cytokines (Th1
      and Th2), chemokines, growth factors, cell-cell interaction, and reorganization
      of matrix proteins. In this article, we briefly present the relevance of Th1 and
      Th2 responses and the significance of interactions between matrix-producing cells
      and inflammatory cells during granuloma tissue and scar tissue formation.

PMID- 15449106
TI  - Helicobacter pylori infection and gastric cancer.
AB  - Helicobacter pylori infection has an association with histological gastritis,
      gastric atrophy, gastric cancer, and mucosa-associated lymphoid tissue (MALT)
      lymphoma in the stomach. Gastric cancer occurs in only a minority of infected
      individuals, however. Such clinical diversities are caused by variations of H.
      pylori pathogenicity, host susceptibility, environmental factors, and
      interactions of these factors. By three prospective epidemiological studies, the
      International Agency for Research on Cancer, World Health Organization (IARC/WHO)
      concluded in 1994 that H. pylori had a causal linkage to gastric carcinogenesis
      and is a definite carcinogen in humans. In addition, the Mongolian gerbil model
      with or without low-dose chemical carcinogens demonstrated that H. pylori
      infection could develop into gastric cancer. The experimental studies have
      elucidated that virulence factors of H. pylori have an interaction with gastric
      epithelial cell signaling related to carcinogenesis. The cag pathogenicity island
      (cagPAI) is a major virulence gene cluster and codes the type IV secretion
      machinery system, forming a cylinder-like structure. The CagA protein is
      translocated into target cells via this secretion system and induces a
      hummingbird morphology, growth factor-like effect. The other gene products are
      probably translocated into target cells and accelerate cellular proliferation and
      apoptosis. Understanding the molecular mechanism of the interaction between H.
      pylori and gastric epithelial cells will provide us with a new strategy for
      effective prevention of the development of gastric cancer induced by H. pylori
      infection.

PMID- 15449107
TI  - Specific gene suppression using antisense strategy for growth suppression of
      glioma.
AB  - Antisense strategy using synthetic oligodeoxynucleotides has been applied to the
      suppression of specific gene expression, the modulation of various gene
      expression, and its biological activity. Antisense strategy is applicable for the
      growth suppression of glioma cells. Several genes, including transforming growth
      factor-alpha, basic fibroblast growth factor, fibroblast growth factor receptor
      1, vascular endothelial growth factor, telomerase, topoisomerase II alpha
      subunit, protein kinase C-alpha, and microtubule-associated protein 1A, have been
      targeted by antisense strategy in glioma cells. These antisense strategies
      provide a potential novel antitumor therapy for gliomas.

PMID- 15449109
TI  - Tissue specificity of apoptotic signal transduction.
AB  - Two major apoptotic pathways exist in mammalian cells: the death receptor and
      mitochondrial pathways. The cross talk between these two pathways is minimal, and
      they operate basically independent of each other under physiological conditions.
      Therefore, the tissue specificity of the signal pathway during apoptosis is
      observed in various tissues and organs. In this article, I demonstrate several
      examples of apoptosis induced by different signal pathways: apoptosis of human
      amniotic epithelial cells upon fetal membrane rupture induced by the death
      receptor pathway, apoptosis of human endometrial cells shed via menstruation and
      in the selection of B cells in gut-associated lymphoid tissues induced by both
      the death receptor and mitochondrial pathways, and apoptosis of lovastatin
      induced breast cancer cells induced by the mitochondrial pathway.

PMID- 15449110
TI  - Changed expression of heat shock proteins in various pathological findings in
      placentas with intrauterine fetal growth restriction.
AB  - Heat shock proteins (HSPs) are activated in the cells of most organisms in
      response to sublethal heat shock and other stressors. It has been reported that
      HSP27, HSP60, HSP70, and HSP90 are expressed in normal human placenta, and it was
      thought that these HSPs play a role in the demonstration of cell viability and
      function. In this study, we performed an immunohistochemical (IHC) study of these
      HSPs for 27 placentas that had complicated intrauterine fetal growth restriction
      (IUGR) and compared the IHC findings with the pathological findings. To quantify
      HSP27, HSP60, HSP70, and HSP90, immunoreacted cells in the chorionic villi,
      syncytiotrophoblasts (ST), and cytotrophoblasts (CT) were counted. In thrombus,
      excessive syncytial knots, and avascular villi, the expression of HSPs was higher
      in the pathological sections compared to control in both ST and CT. In contrast,
      all HSPs decreased in both ST and CT around the infarction region. The data
      suggested that chorionic villi cells locally responded to some stresses, e.g.,
      hypoxia and increase or decrease in the expression of HSPs. Although the villous
      cells around the infarction histologically appear viable, they may have received
      lethal damage, and as a result the expression of HSPs was decreased. These
      results are expected to improve our understanding of the pathological findings of
      IUGR in placentas, including the quality, damage, and function of the chorionic
      villi.

PMID- 15449111
TI  - Ultrastructural characterization of the distribution of melanin and epidermal
      macrophages in photodamaged skin.
AB  - We examined the characteristics of melanin distribution, the possible mechanisms
      underlying the histological incontinence of pigment, and the significance of
      epidermal macrophages in photodamaged skin. We used electron microscopy to
      compare and quantitate melanin distribution in various types of cells and
      structures, to qualitatively observe associations of melanin granules with
      melanophages, and to examine morphological differences of epidermal macrophages
      in sun-exposed versus sun-protected facial skin. Melanin-containing cells (such
      as Langerhans' cells) and melanin-containing structures (such as colloid bodies)
      in photodamaged skin were more numerous than in sun-protected skin, in proportion
      to differences in melanocyte density and in epidermal melanin content. Although
      the precise mechanism(s) of histological incontinence of pigment in photoaging
      skin appear to be very complicated, it is certainly one of the morphological
      hallmarks of photodamaged facial skin, and the degeneration of keratinocytes
      (noted by their electron-lucent properties), a feature characteristic of
      photoaging, contributes to that process. Furthermore, the increased numbers of
      epidermal macrophages in sun-exposed skin may be associated with photoaging
      processes (probably through their phagocytic function) as well as alterations of
      the cutaneous immune system.

PMID- 15449112
TI  - K-ras mutation may promote carcinogenesis of endometriosis leading to ovarian
      clear cell carcinoma.
AB  - Endometriosis shares some features characteristic of malignancy; however, it
      remains unclear whether endometriosis is a precursor to malignant disease. The
      objective is to determine the genetic relationship between endometriosis and
      ovarian clear cell carcinoma (OCCA). Among 37 Japanese patients with OCCA who
      underwent primary surgery at Showa University Hospital between 1987 and 1999, K
      ras mutations were detected in 6. Three of these patients had ectopic endometrial
      tissue adjacent to the site of carcinoma. These cases demonstrated areas of
      endometriosis and areas of OCCA bordered by atypical endometriosis. We retrieved
      cells from regions of endometriosis and atypical endometriosis, as well as OCCA
      cells, by laser microdissection in each case. K-ras mutations were analyzed in
      each specimen dissected. DNA analysis of each region revealed that K-ras
      mutations were detectable in OCCA but not in endometriosis or atypical
      endometriosis. It is thought that a number of genetic alterations are involved in
      malignant transformation. It is possible that K-ras mutations are associated with
      malignant transformation of atypical endometriosis into OCCA, although further
      research is needed to define this mechanism.

PMID- 15449113
TI  - Unique cellular features of peripheral primitive neuroectodermal tumor:
      ultrastructural evidence of its unique cytodifferentiation.
AB  - We present a case of primitive neuroectodermal tumor (PNET) showing a unique
      differentiation phenotype based on ultrastructural observation. Rapidly growing
      tumor involving the retroperitoneum of a 68-year-old woman was characterized by
      histological findings including proliferation of diffuse poorly differentiated
      small round cells with scattered rosette formation similar to Homer-Wright type
      and by the ultrastructure demonstrating cytoplasmic neurosecretary granules and
      short cytoplasmic cilial structures. These cells revealed immunoreactivity only
      with neuron-specific enolase (NSE). We also observed a chromosomal translocation,
      t (11; 22) (q24; q12), which is an identical recurrent alteration found in the
      neoplastic cells in the spectrum of PNETs. These findings may support the
      explanation that tumor cells observed in our case shared phenotypes of both
      neuronal and ependymal cell lineages and give a unique insight suggesting the
      possible histogenesis of PNETs.

PMID- 15449114
TI  - Antimicrobial effects of a new therapeutic liquid dentifrice formulation on oral
      bacteria including odorigenic species.
AB  - The control of oral malodor is well-recognized in efforts to improve oral health.
      Antimicrobial formulations can mitigate oral malodor, however, procedures to
      assess effects on oral bacteria including those implicated in halitosis are
      unavailable. This investigation examined the antimicrobial effects of a new
      liquid triclosan/copolymer dentifrice (test) formulation that demonstrated
      significant inhibition of oral malodor in previous organoleptic clinical studies.
      Procedures compared antimicrobial effects of the test and control formulations on
      a range of oral micro-organisms including members implicated in halitosis,
      substantive antimicrobial effects of formulations with hydroxyapatite as a
      surrogate for human teeth and ex vivo effects on oral bacteria from human
      volunteers. With Actinomyces viscosus, as a model system, the test formulation
      demonstrated a dose-dependent effect. At these concentrations the test
      formulation provided significant antimicrobial effects on 13 strains of oral
      bacteria including those implicated in bad breath at selected posttreatment time
      points. Treatment of hydroxyapatite by the test dentifrice resulted in a
      significant and substantive antimicrobial effect vs. controls. Oral bacteria from
      subjects treated ex vivo with the test dentifrice resulted in significant
      reductions in cultivable oral bacteria and odorigenic bacteria producing hydrogen
      sulfide. In summary, microbiological methods adapted to study odorigenic bacteria
      demonstrate the significant antimicrobial effects of the test
      (triclosan/copolymer) dentifrice with laboratory and clinical strains of oral
      bacteria implicated in bad breath.

PMID- 15449116
TI  - Nationwide survey on complications of spine surgery in Japan.
AB  - The Japan Spine Research Society carried out a nationwide survey on complications
      of the spine, enrolling a total of 16 157 patients who had undergone spine
      surgery in 196 institutes in the 1-year period from January to December 2001.
      Diseases, surgical procedures, and complications were surveyed in detail. Forty
      nine percent of patients were aged 60 years or older, which was remarkably
      increased in comparison with the percentage reported by the 1994 survey (37.3%).
      The number of cases with degenerative spinal diseases comprised 78.2% of the
      total number of spine surgery cases. The percentage of patients with stenosis was
      the greatest (38.5%), reflecting the increase in the elderly population
      undergoing spine surgery. Spinal instrumentation was used with 5497 patients
      (34.0%). The frequency of its use was much greater than that reported in 1994
      (27.0%). The pedicle screw was the most frequently used instrument (54.6%). The
      use of spinal instrumentation greatly increased for spinal deformity, trauma, and
      tumors. Posterior lumbar interbody fusion has been increasingly used in cases of
      lumbar degenerative disease. Complications of spinal surgery were reported in
      1383 patients (8.6%). The incidence of complications associated with
      instrumentation surgery was 12.1%, being twice as much as that associated with
      noninstrumentation surgery (6.8%).

PMID- 15449117
TI  - New preoperative evaluation system of the physical findings of aged patients with
      femoral neck fracture.
AB  - We devised our own method of evaluating a patient's general condition at
      admission, and estimated the usefulness of this method for evaluating patients
      with femoral neck fractures and its relationship to prognosis, in particular,
      factors influencing poor functional and vital prognoses. We examined 83 patients
      between January 1992 and March 1996 who had been treated for more than 30 days
      after injury and had no malignant tumor as an underlying disease. The new
      criteria for systemic status evaluation at admission were chosen by reference to
      the preoperative status classification system of the American Society of
      Anesthesiologists. Three evaluation grades were established for each of eight
      items (pulmonary function, heart disease, hypertension, glucose tolerance
      impairment, renal function, hepatic function, anemia, and hypoproteinemia).
      Pulmonary function and heart disease were evaluated on a 20-point scale, and the
      other six items on a 10-point scale; the maximum possible score was 100 points.
      Scores were statistically analyzed in relation to functional and vital prognoses.
      Poor prognosis factors were determined and ranked. We found that the factors
      associated with a poor functional prognosis were heart disease, glucose tolerance
      impairment, and pulmonary dysfunction, and those associated with a poor vital
      prognosis were renal dysfunction and glucose tolerance impairment.

PMID- 15449118
TI  - Simple screening method for deep vein thrombosis by duplex ultrasonography using
      patients' active maximum ankle dorsiflexion.
AB  - We hypothesized that venous obstruction by deep vein thrombosis (DVT) only
      slightly augments venous outflow from lower limbs by active ankle movements. If
      our hypothesis is true, we thought that we could develop a new screening method
      for DVT using duplex ultrasonography. Subjects were 22 lower limbs of 11 patients
      who gave informed consent for venography after total hip or knee arthroplasty.
      Around postoperative 19.0 days (range 15-32 days), we measured the ratios, called
      flow ratios, of the peak flow signal with active maximum ankle dorsiflexion and
      that at rest using duplex ultrasonography in the bilateral femoral veins. On the
      same day, we then performed bilateral venography. Thrombosis was detected in 5 of
      the 22 lower limbs. The mean flow ratios with and without DVT were 1.18 (range
      1.0-1.3) and 3.31 (range 1.8-4.8), respectively. The flow ratios with DVT were
      significantly lower than those without DVT. Pain or difficulty performing active
      maximum ankle dorsiflexion was not observed in any of the operated or unoperated
      lower limbs during the ultrasound examination. In conclusion, ultrasonographic
      measurement of flow ratios may become a simple screening method for DVT in lower
      limbs without the pain or difficulty of performing active maximum ankle
      dorsiflexion.

PMID- 15449119
TI  - Axial radiographic evaluation in hallux valgus: evaluation of the transverse arch
      in the forefoot.
AB  - To quantitatively evaluate the shape of the transverse arch in the forefoot with
      hallux valgus, a method for axial imaging and analysis of the forefoot has been
      developed. A foot was imaged at 30 degrees of flexion. A two-dimensional
      coordinate system was established by drawing a vertical line on the X-ray image
      through the lowest point of the head of the second metatarsal. The origin was set
      at the intersection between the plane of the base of the foot and this vertical
      line. A control group of 51 feet from 29 normal subjects and a test group of 59
      feet from 34 subjects with hallux valgus were examined. Compared with the normal
      group, the heads of the first, second, and third metatarsal bones were lower in
      the hallux valgus group, and their sesamoids were shifted outward with a
      rotational deviation. There was a statistical correlation between the degree of
      outward dislocation of the fibular sesamoid bone and the hallux valgus angle. The
      position of the fibular sesamoid bone become higher than the head of the first
      metatarsal when the angle of the hallux valgus exceeded 25 degrees.

PMID- 15449120
TI  - Clinical accuracy evaluation of femoral canal preparation using the ROBODOC
      system.
AB  - The purpose of this study was to evaluate the clinical accuracy of femoral canal
      preparation using postoperative reconstructed computed tomography (CT) images of
      75 consecutive total hip arthroplasties performed with a two-pin-based ROBODOC
      system. Intraoperatively, the robot milled the femoral canal according to the
      preoperative planning performed with preoperative CT data and the ROBODOC
      workstation. Postoperative CT data was obtained 1 month postoperatively.
      Anteroposterior and lateral synthetic radiographs and axial images were
      reconstructed from CT data on the workstation. The mean difference between the
      preoperative planning and the postoperative CT images was less than 5% in canal
      fill, less than 1 mm in gap, and less than 1 degrees in the mediolateral and
      anteroposterior alignment. Clinical femoral canal preparation using the ROBODOC
      system results in a high degree of accuracy.

PMID- 15449121
TI  - Grit-blasted and hydroxyapatite-coated total hip arthroplasty: an 11- to 14-year
      follow-up study.
AB  - We report long-term results of the first clinical trial of hydroxyapatite-coated
      total hip arthroplasty conducted in Japan. The hemispherical cup and the straight
      tapered stem were made of titanium alloy with a grit-blasted, hydroxyapatite
      coated surface. The surface roughness before and after hydroxyapatite coating was
      1.4 microm and 3.4 microm, respectively. Thirty-three patients (35 hips) were
      followed prospectively; of these, 1 patient was lost to follow-up, 5 were
      deceased at the latest follow-up, and 27 were followed for 11 to 14 years. Two
      cups and one stem (two patients) were revised. Survivorship, with radiological
      acetabular loosening as the endpoint, was 62.3% at 14 years. At the latest
      radiological follow-up, stable fixation with bone ongrowth was achieved in 46% of
      the acetabular cups and 89% of the femoral stems. Acetabular cups with host bone
      coverage of less than 60% had a high rate of failure. The suboptimal result of
      the hydroxyapatite-coated smooth cup indicates that porous coatings under the
      hydroxyapatite coating would be beneficial for hydroxyapatite-coated total hip
      implants, especially for the acetabular components.

PMID- 15449122
TI  - Morphometry of the lumbar zygapophyseal facet capsule and cartilage with special
      reference to degenerative osteoarthritic changes: an anatomical study using fresh
      cadavers of elderly Japanese and Korean subjects.
AB  - Morphometric data were obtained from fresh cadaver dissections, and observations
      of degenerative changes in the joint cartilage (DCs) were analyzed to determine
      whether the morphometric parameters of the lumbar zygapophyseal joint capsule
      varied according to the presence and severity of DCs. There have been no previous
      morphometric studies of the facet capsule that describe age-related DCs. Using 23
      fresh osteoligamentous lumbar spines from donated cadavers, we performed
      morphometric investigations of the surface areas of the joints and their capsules
      and measured the capsular thickness. We hypothesized that the ratio of the inner
      capsular area to the joint surface area for each facet (the capsule/facet index)
      could serve as an index showing a functional aspect of a large or small capsule.
      Our results showed that the joint surface area increased significantly with
      increasing severity of DCs, according to Grogan's classification. Facets with
      advanced DCs tended to have a small inner capsular surface. The capsule/facet
      index generally correlated positively with capsular thickness, especially the
      dorsal portion; however, this was not true for the ventral portion. The index
      also correlated negatively with DC progression. Thus, lumbar facet DCs were
      strongly linked to reconstructive alterations in capsular size, thickness, and
      looseness. The occurrence and progression of DCs narrowed the joint capsule,
      especially the dorsal portion, and this seemed to decrease the potential
      looseness of the joint. Conversely, these capsular alterations seemed to
      accelerate DC progression. A negative adaptation cycle seemed to occur.

PMID- 15449123
TI  - Histological analysis and biological effects of granulation tissue around
      loosened hip prostheses in the development of osteolysis.
AB  - Although aseptic loosening of the prosthesis is a long-term complication after
      total joint replacement, the detailed mechanism of osteolysis remains unknown. We
      examined 82 samples from 40 patients with aseptic loosened hip prostheses
      histologically, and compared the distribution of particles,
      macrophages/histiocytes, and foreign body giant cells in the retrieved tissue
      from capsules and around prostheses. Furthermore, to investigate the mechanism of
      osteolysis, we cultured tissue from a patient with massive osteolysis and
      examined the effects of the conditioned medium on osteoblasts in vitro. Numerous
      multinucleated giant cells and histiocytes were present, and polyethylene
      particles ranging from medium to large were identified in the polarized light.
      However, the distribution was heterogeneous, and no particles were found
      microscopically in about 30%-40% of periprosthetic tissues, and in 60% of
      capsules. The amount of particles correlated with giant cells, but not with
      histiocytes. The conditioned medium of the granulation tissue culture stimulated
      osteoblasts to produce interleukin-6 in both protein and mRNA, and this was in
      part inhibited by anti-tumor necrosis factor-alpha or the interleukin-1beta
      antibody, suggesting that interleukin-6 production is mediated by several
      cytokines. These findings suggest that interleukin-6, which is produced not only
      by macrophages but also by osteoblasts, is a contributing factor to aseptic
      loosening.

PMID- 15449124
TI  - The effect of cell-based therapy with autologous synovial fibroblasts activated
      by exogenous TGF-beta1 on the in situ frozen-thawed anterior cruciate ligament.
AB  - The present study was conducted to clarify the effect of cell therapy with
      autologous synovial tissue-derived fibroblasts activated by transforming growth
      factor (TGF)-beta1 on the necrotized anterior cruciate ligament (ACL). Thirty-six
      mature female Japanese white rabbits were used in this study. In Group I, fibrin
      glue with autologous synovial tissue-derived fibroblasts after TGF-beta
      stimulation was wrapped around the necrotized ACL after freeze-thaw treatment. In
      Group II, the glue without TGF-beta stimulation was wrapped around the frozen
      thawed ACL. In Group III, the fibrin glue without fibroblasts was applied in the
      same manner on the frozen-thawed ACL. Histological observation found that
      implantation of fibroblasts after TGF-beta stimulation accelerated cellular
      infiltration into the ACL following fibroblast necrosis. Biomechanically, the
      transplantation of synovial tissue-derived autologous fibroblasts activated by
      TGF-beta inhibited mechanical deterioration of the ACL after the freeze-thaw
      treatment. The present study has shown that cell-based therapy using synovial
      tissue-derived fibroblasts activated by TGF-beta1 is a possible solution to
      mechanical deterioration of the graft after ACL reconstruction.

PMID- 15449125
TI  - Animal model of chondrocyte apoptosis in the epiphyseal cartilage of the neonatal
      bone.
AB  - Apoptosis is considered to be the mechanism responsible for the death of
      chondrocytes during endochondral bone formation. It is also claimed that
      apoptosis of the chondrocytes is age related and that the apoptotic index
      increases with age. However, a detailed analysis of the apoptotic activity of the
      neonatal epiphyseal cartilage is lacking. A model that evaluates apoptosis in the
      femoral rat epiphyseal cartilage both quantitatively and qualitatively is
      reported. Apoptotic incidence in the epiphyseal cartilage reached a maximum at
      age 6 days, but the age in our study did not significantly affect the percentile
      rate of apoptotic chondrocytes (P > 0.05, Kruskal-Wallis test). Apoptosis in the
      zone of hypertrophic cartilage played the most important role in the growth
      plate's homeostasis. Morphologic evidence of apoptosis was necessary in addition
      to positive nick end labeling of cells. Electron microscopy studies revealed
      atypical modes of programmed death of the growth plate chondrocytes in addition
      to the classical apoptotic mode.

PMID- 15449126
TI  - Bone morphogenetic protein-2 induces differentiation of multipotent C3H10T1/2
      cells into osteoblasts, chondrocytes, and adipocytes in vivo and in vitro.
AB  - Mesenchymal stem cells capable of differentiating into multiple cell types are
      potentially useful therapeutically for regeneration of bone and cartilaginous
      tissues. Multipotent fibroblastic C3H10T1/2 cells are known to differentiate into
      osteoblasts, chondrocytes, and adipocytes in response to certain growth factors.
      In this study we compared the effects of bone morphogenetic protein (BMP)-2 on
      the differentiation of C3H10T1/2 and MC3T3-E1 preosteoblastic cells. Incubation
      of these cells with BMP-2 resulted in a dose- and time-dependent increase in
      alkaline phosphatase activity, but the increase in MC3T3-E1 cells was much higher
      than that in C3H10T1/2 cells. BMP-2 also induced differentiation of C3H10T1/2
      cells but not MC3T3-E1 cells into chondrocytes and adipocytes. Reverse
      transcription-polymerase chain reaction analysis showed that these commitments
      were accompanied by the specific expression of osteocalcin, aggrecan, and
      PPARgamma. To investigate the in vivo differential property, these cells were
      inoculated with BMP-2 in a diffusion chamber and transplanted into the mouse
      peritoneal cavity for 4 weeks. The transplanted C3H10T1/2 cells formed
      mineralized bone containing chondrocytes and adipocytes, whereas MC3T3-E1 created
      only bony tissue. Our results indicate that BMP-2 can induce the differentiation
      of C3H10T1/2 into osteoblasts, chondrocytes, and adipocytes in both in vivo and
      in vitro conditions, and that C3H10T1/2 could be used to examine the BMP-2
      induced regulatory mechanisms of mesenchymal differentiation.

PMID- 15449127
TI  - Oxidative stress and vascular permeability in steroid-induced osteonecrosis
      model.
AB  - We focused on the role of oxidative stress in the pathogenesis of steroid-induced
      osteonecrosis (ON) and the possibility of preventing this condition by
      antioxidant administration. Methylprednisolone 4 mg/kg was injected only once
      into Japanese white rabbits. The involvement of oxidative stress and the
      presence/absence of bone circulatory impairment were investigated in groups of 10
      rabbits killed at 3, 5, and 14 days each and in 10 rabbits administered the
      antioxidant glutathione. Reduced blood glutathione and lipid peroxide levels were
      determined biochemically, and the presence/absence of advanced glycation end
      product expression was determined immunohistochemically. Vascular permeability in
      bone was confirmed by finding albumin leakage into the stroma. These blood
      biochemical and immunohistochemical studies clarified that the oxidative stress
      in this model developed 3-5 days after steroid administration. Elevated vascular
      permeability was observed in the 5- and 14-day groups. Hence, circulatory
      disturbance in bone was noted 5 days after steroid administration, coinciding
      with the onset of oxidative stress. The rate of ON development, which was 70% in
      the steroid-alone 14-day group, was significantly reduced to 0% in the steroid +
      antioxidant group. These results suggest the involvement of oxidative stress and
      vascular permeability in this steroid-induced ON model and the possibility of its
      prevention by suppression of oxidative stress.

PMID- 15449128
TI  - Osteofibrous dysplasia treated with distraction osteogenesis: a report of two
      cases.
AB  - We treated two patients with osteofibrous dysplasia of the tibia using en bloc
      marginal excision of the lesion and bone transport, a distraction osteogenesis
      procedure. In one patient, we had performed curettage procedures twice, each time
      followed by local recurrence and deformity. In contrast, with marginal excision
      and bone transport using an Ilizarov apparatus, the disease healed. In the other
      patient, we performed marginal excision and bone transport as the first
      procedure, which resulted in a healed lesion. In patients with osteofibrous
      dysplasia requiring treatment by an open method, curettage frequently is followed
      by local recurrence and deformity. We now prefer marginal excision of the lesion
      to avoid long-term failures, as in our first case. Distraction osteogenesis has
      proven useful for restoring structure and function in the affected limb.

PMID- 15449129
TI  - Oral alendronate treatment for polyostotic fibrous dysplasia: a case report.
AB  - Recently, intravenous therapy with pamidronate has been reported to be effective
      for treating fibrous dysplasia. However, very little is known about the efficacy
      of oral alendronate for fibrous dysplasia. We describe a patient with polyostotic
      fibrous dysplasia, who had complained of persistent pain for more than 20 years,
      that was treated with oral alendronate alone. Follow-up examinations were at
      intervals of 3 months for 2 years. The pain, radiographic findings, and bone
      turnover, which was monitored using various markers, improved. No adverse side
      effect was noted. Oral alendronate is suggested to be a useful option in the
      treatment of polyostotic fibrous dysplasia.

PMID- 15449130
TI  - Concomitant double epiphyseal injuries of the tibia with vascular compromise: a
      case report.
AB  - A rare case of double epiphyseal injuries in the same tibia is reported. A 4-year
      old child was struck by a vehicle and presented with the above fractures and
      vascular compromise to the extremity. Following localization of the vascular
      occlusion level by arteriography, popliteal vessel anastomosis was attempted. The
      vascular repair failed, resulting in disarticulation through the knee.
      Simultaneous displaced proximal and distal epiphyseal injury in the same tibia
      has not been previously reported in the literature. The most serious complication
      of injury to the proximal tibia is vascular compromise. A delay in recognition or
      intervention in such cases can be devastating.

PMID- 15449131
TI  - Contrast-enhanced magnetic resonance imaging of malignant granular cell tumor
      with pathological correlation: a case report.
AB  - This report presents a case of malignant granular cell tumor in the deltoid
      muscle and emphasizes the correlation between magnetic resonance (MR) images and
      pathological findings. A 71-year-old woman developed an elastic hard mass at the
      left shoulder. MR images revealed a soft tissue tumor with a maximum diameter of
      5 cm and low signal intensity on both T1- and T2-weighted images. The lesion with
      decreased signal intensity on all the images correlated with marked fibrosis
      mimicking desmoid tumor. Contrast-enhanced MR images provided useful information
      regarding the choice of biopsy site.

PMID- 15449132
TI  - Experimental models of osteonecrosis of the femoral head.

PMID- 15449133
TI  - Mechanistic insight into the catechol oxidase activity by a biomimetic dinuclear
      copper complex.
AB  - The biomimetic catalytic oxidation of 3,5-di- tert-butylcatechol by the
      dicopper(II) complex of the ligand alpha,alpha'-bis(bis[1-(1'-methyl-2'
      benzimidazolyl)methyl]amino)- m-xylene in the presence of dioxygen has been
      investigated as a function of temperature and pH in a mixed aqueous/organic
      solvent. The catalytic cycle occurs in two steps, the first step being faster
      than the second step. In the first step, one molecule of catechol is oxidized by
      the dicopper(II) complex, and the copper(II) centers are reduced. From the pH
      dependence, it is deduced that the active species of the process is the
      monohydroxo form of the dinuclear complex. In the second step, the second
      molecule of catechol is oxidized by the dicopper(I)-dioxygen complex formed upon
      oxygenation of the reduced complex. In both cases, catechol oxidation is an inner
      sphere electron transfer process involving binding of the catechol to the active
      species. The binary catechol-dicopper(II) complex formed in the first step could
      be characterized at very low temperature (-90 degrees C), where substrate
      oxidation is blocked. On the contrary, the ternary complex of dicopper(I)-O(2)
      catechol relevant to the second step does not accumulate in solution and could
      not be characterized, even at low temperature. The investigation of the biphasic
      kinetics of the catalytic reaction over a range of temperatures allowed the
      thermodynamic (Delta H degrees and Delta S degrees ) and activation parameters
      (Delta H( not equal) and Delta S( not equal)) connected with the key steps of the
      catecholase process to be obtained.

PMID- 15449134
TI  - Molecular characterization of the first isolation of rotavirus in guanacos (Lama
      guanicoe).
AB  - Rotaviruses (RVs) are a major cause of neonatal diarrhoea in humans and numerous
      animal species. We report G-type, P-type and phylogenetic analysis of two RV
      strains isolated from newborn guanacos (Lama guanicoe) with acute diarrhoea in
      Argentina. Isolates were group A G8 RV. Phylogenetic analysis showed a close
      relationship to other G8 bovine RV from Japan, U.S.A. and Switzerland. P-types
      were P[1] and an unusual P[14], related to human and goat P[14] strains. This is
      the first report of a P[14]G8 strain in our country and the first study on
      molecular epidemiology of rotavirus found in a new species.

PMID- 15449135
TI  - A novel multiplex RT-PCR system detects human endogenous retrovirus-K in breast
      cancer.
AB  - Human endogenous retrovirus HERV-K like-sequences have been implicated in certain
      cancers. We developed a novel multiplex RT-PCR system for HERV-K that yielded a
      533 bp product together with a smaller sized product (319 bp) of the house
      keeping gene, histidyl tRNA synthetase (HtRNAS). The latter spanned an intron
      that also served to validate target cDNA. PCR amplicons of HERV-K and HtRNAS were
      visualised using a gel documentation system and the pixel intensity used to
      derive semi-quantitative levels of viral expression. Our data showed that HERV
      K10 was significantly elevated in MCF-7 cells treated with estrogen.
      Interestingly, HERV-K expression was higher in MCF-7 cells selected with
      adriamycin. RT-PCR combined with Southern blotting also detected HERV-K from
      breast cancer tissue using laser capture microscopy. This study highlights the
      presence of HERV-K in the breast cancer cell lines MCF-7 and MCF-7 ADR and
      confirms HERV-K10 transcripts in the cell line T47D. We believe this study to be
      a novel approach in determining levels of HERV-K expression and for detecting
      this virus in cancer cell lines and tissues.

PMID- 15449136
TI  - Yeast two-hybrid systems confirm the membrane- association and oligomerization of
      BC1 but do not detect an interaction of the movement proteins BC1 and BV1 of
      Abutilon mosaic geminivirus.
AB  - Most of the plant begomoviruses use two proteins to transport their DNA from cell
      to cell, BV1 to shuttle it between nucleus and cytoplasm and BC1 to facilitate
      movement across plasmodesmata. In order to analyse their interaction for Abutilon
      mosaic geminivirus (AbMV) in yeast ( Saccharomyces cerevisiae), BC1 and BV1 genes
      were cloned into various plasmid vectors suitable for two-hybrid analysis. BC1
      was fused to the binding domain (GBD) and BV1 to the activation domain (GAD) of
      the GAL4 transcription factor to check for interactions in the nucleus.
      Additionally, BC1 as well as BV1 were integrated into pMyr or pSos vectors to
      analyze protein binding at the plasma membrane using the CytoTraptrade mark
      system. Using freeze-fracture immuno-labelling (FreeFI), singly-expressed GBD:BC1
      was localized at the plasma membrane although it was fused to a nuclear
      localization signal provided by the construct. GAD:BV1 was found in the nucleus
      of transformed cells as expected. Upon co-transformation of both constructs,
      cells grew poorly and exhibited symptoms of autolysis without any detectable
      level of GBD:BC1 or GAD:BV1, as revealed by FreeFI. In conclusion, both fusion
      proteins did not meet in the same compartment and appeared to be harmful to yeast
      if constitutively co-expressed. When expressed from pSos vector, BC1 induced the
      CytoTrap detection signal in the absence of pMyr indicating that BC1 protein
      alone is able to target the effector protein to the inner face of the plasma
      membrane. A mutated form of BC1 (DeltaBC1) lacking the previously identified
      membrane-binding domain was no longer able to auto-induce the CytoTrap signal
      cascade. Using DeltaBC1, an N-terminal, or a C-terminal third of BC1 revealed a
      homo-oligomerization of the C-terminal region of BC1 in two-hybrid analysis, but
      no interaction of BC1 with BV1.

PMID- 15449137
TI  - Little cherry virus-2: sequence and genomic organization of an unusual member of
      the Closteroviridae.
AB  - The complete genomic sequence of variant USA6b of Little cherry virus-2 (LChV-2),
      has been determined and is 15045 nucleotides in length, coding for 11 open
      reading frames (ORFs). The sequence shares 77.2% identity with a previously
      published, ca. 6 kb partial replicase sequence of LChV-2 (variant USA6a). Both
      LChV-2/USA6a and LChV-2/USA6b were obtained from the same tree infected with
      little cherry disease, and would suggest a mixed infection. LChV-2/USA6b is more
      closely related to the partially determined genomic sequence of a Canadian
      isolate of LChV-2, strain LC5 (92.9% identity). LChV-2/USA6b has an unusual
      genomic organization compared to other members of the Closteroviridae. The LChV
      2/USA6b genome is potentially ambi-sense, with a negative sense ORF0 at the 5'
      terminus, from which an 18.1 kDa protein of unknown function can be expressed in
      vitro. The N-terminal region of the LChV-2/USA6 ORF1a translation product does
      not code for a papain-like protease motif. ORF1 codes for a novel motif, of
      unknown function, also present in isolates of the Grapevine leafroll associated
      virus-3, (genus Ampelovirus) as well as viruses of the family Flexiviridae. ORF3
      lacks an AUG start codon, but could potentially be expressed via read-through of
      the ORF2 stop codon. At the 3' end, there is a re-organization of encoded genes
      compared with other members of the Closteroviridae including separation of the
      coat protein and coat protein duplicate genes by 4 other genes as found for LChV
      2/LC5.

PMID- 15449138
TI  - Transient in vivo gene delivery to the silkworm Bombyx mori by EGT-null
      recombinant AcNPV using EGFP as a reporter.
AB  - Several strains of silkworm Bombyx mori were tested for the gene delivery
      feasibility of Autographa californica nucleopolyhedrovirus (AcNPV) in vivo. In
      contrast to the general belief that silkworms were non-permissive to AcNPV, we
      found that 3 of 7 tested strains were AcNPV permissive. To dispel the
      physiological influence of the ecdysteroid UDP-glucosyltransferase (EGT) on the
      silkworm, we modified the AcNPV bacmid by disruption of that gene. Expression
      pattern of EGFP in tissues of silkworm larvae after injection of EGT-null AcNPV
      vector carrying EGFP cassette was revealed by green fluorescence and Western blot
      analysis. Viral DNA was detected and semi-quantified in various kinds of tissues
      by dot blot assay. Active recombinant virus from larval hemolymph was detectable
      by TCID(50). Our results indicate that some strains of silkworm were permissive
      to AcNPV, which could serve as a novel gene deliver tool to silkworm in vivo.

PMID- 15449139
TI  - Delayed viremia and antibody responses in Puumala hantavirus challenged passively
      immunized cynomolgus macaques.
AB  - No specific therapy is currently available against hemorrhagic fever with renal
      syndrome (HFRS) or hantavirus pulmonary syndrome. In order to study if passive
      immunization could inhibit hantavirus infection and/or symptoms, we inoculated
      two cynomolgus macaques with neutralizing monoclonal antibodies and subsequently
      challenged them with wild-type Puumala virus (PUUV), recently shown to induce
      typical signs of milder HFRS in cynomolgus macaques. Although viral load and
      antibody titers did not differ substantially as compared to the two control
      monkeys, a delayed onset of viremia and seroconversion was observed in the
      immunized monkeys. Interestingly, one of the immunized monkeys showed no
      symptoms, nor elevated of levels of IL-6, IL-10, and TNF-alpha, while the other
      developed severe symptoms and elevated levels of those cytokines, believed to be
      involved in PUUV-pathogenesis.

PMID- 15449140
TI  - Further molecular characterisation of potyviruses infecting aroid plants for
      medicinal use in China.
AB  - Degenerate primers were used to detect and amplify 3'-terminal genome fragments
      of potyviruses from medicinal aroid plants growing at 16 sites in China. Virus
      was detected in 7 samples of which six, all of Pinellia ternata, contained a
      strain of soybean mosaic virus (SMV) similar to that previously reported from
      this host in China. The complete sequence of one isolate and the P1 protein
      coding region of the other isolates were also sequenced. In all cases, the P1
      proteins resembled isolates of Dasheen mosaic virus (DsMV) more closely than SMV,
      confirming earlier suggestions of recombination in this region. In a phylogenetic
      analysis of SMV, DsMV and related sequences, the aroid sequences of SMV formed a
      distinct group which also included a sequence published as Zantedeschia
      symptomless virus (AF469171). One of the P. ternata samples was also infected
      with a second potyvirus, the 3'-terminal sequence of which was similar to DsMV
      and to some sequences published as Vanilla mosaic virus. The seventh infected
      sample was Typhonium flagelliforme and the virus from it was identified from its
      sequence as zantedeschia mosaic virus (ZaMV), providing the first report of this
      virus from mainland China.

PMID- 15449141
TI  - HIV-1 Vpr enhances production of receptor of activated NF-kappaB ligand (RANKL)
      via potentiation of glucocorticoid receptor activity.
AB  - The HIV-1 accessory protein Vpr potentiates glucocorticoid (GC)-induced
      inhibition of a variety of immunologically important cytokines. We report the
      first instance of synergy between Vpr and GC in induction of a T cell cytokine,
      one which may underlie a metabolic complication of HIV infection. Accelerated
      bone resorption is an important complication of HIV disease and its treatment.
      Receptor of activated NF-kappaB ligand (RANKL) is the final effector of
      osteoclast differentiation and bone resorption. It is induced by exogenous GC, a
      prominent cofactor in bone mineral loss, as well as by elevated levels of
      endogenous GC, found in many patients with HIV disease. We document Vpr-mediated
      upregulation of RANKL, the dependence of this effect on GC receptor integrity,
      its function through a classic GC receptor motif, and its independence from Vpr
      mediated G(2) cell cycle arrest. These data suggest a positive regulatory role
      for Vpr in transcriptional control of a cytokine that may be critical to one
      metabolic complication of HIV.

PMID- 15449142
TI  - Genome sequences of Agropyron mosaic virus and Hordeum mosaic virus support
      reciprocal monophyly of the genera Potyvirus and Rymovirus in the family
      Potyviridae.
AB  - Assignment of mite-transmitted species to the genus Rymovirus (family
      Potyviridae) has changed several times, and the status of the genus has been
      questioned. To address this issue, complete genome sequences of the rymoviruses
      Agropyron mosaic virus (AgMV) and Hordeum mosaic virus (HoMV) were determined.
      AgMV (9540 nucleotides) and HoMV (9463 nucleotides) each encode a single
      polyprotein with proteinase cleavage sites demarcating protein products
      characteristic of monopartite species of the family Potyviridae. Of the described
      species of Potyviridae, AgMV and HoMV are most closely related to each other
      (68.5% nucleotide and 71.6% amino acid sequence identity) and equidistant (about
      53% nucleotide and about 49% amino acid sequence identity) from a third
      rymovirus, Ryegrass mosaic virus (RGMV). Phylogenetic analyses by neighbor
      joining, maximum parsimony, and Bayesian inference each grouped the three
      Rymovirus species in an exclusive clade distinct from a clade containing 34
      species of the genus Potyvirus. Because AgMV, HoMV, and RGMV share a reciprocal
      monophyletic relationship with species of the genus Potyvirus and are divergent
      in sequence and type of vector, the genus Rymovirus should be retained as a
      taxonomic unit within the family Potyviridae.

PMID- 15449143
TI  - Double-stranded RNA pattern and partial sequence data indicate plant virus
      infection associated with the ringspot disease of European mountain ash (Sorbus
      aucuparia L.).
AB  - Double-stranded RNA (dsRNA) has been extracted from tissue of European mountain
      ash trees (Sorbus aucuparia L.) showing typical ringspot and mottling symptoms on
      leaves and a gradual decay in general. A characteristic dsRNA pattern was found
      in leaf samples of symptomatic mountain ash trees from various stands in Germany.
      Bands of dsRNA molecules of approximately 7 kb, 2.3 kb, 1.5 kb, and 1.3 kb,
      respectively, were repeatedly detected. By random primed reverse transcription
      cDNA was synthesised from dsRNA and amplified by degenerate oligonucleotide
      primed PCR. After TA cloning, the cDNA clones obtained were screened with an
      enhanced-chemiluminescence-labelled dsRNA probe. Positive clones were further
      analysed by using them as hybridisation probes in Northern blots of total plant
      RNA and in Southern hybridisation with genomic DNA from Sorbus aucuparia leaves.
      From cDNA clones that were found to be specific for dsRNA in Northern analysis,
      primers were deduced for 5'-RACE analyses and further cloning. Finally, a cDNA
      fragment of 3,737 bp was obtained, which showed homology to viral proteins,
      particularly to the RNA-dependent RNA polymerase of members of the family
      Bunyaviridae, but without high similarity to a known genus. The dsRNA pattern and
      the sequence information strongly indicate a virus associated with the mountain
      ash ringspot disease. The putative virus remains still unidentified.

PMID- 15449144
TI  - The complete nucleotide sequence of a Spanish isolate of Citrus psorosis virus:
      comparative analysis with other ophioviruses.
AB  - The complete genomic sequence (11278 nt) of Citrus psorosis virus (CPsV), isolate
      P-121 from Spain, was determined and compared with those from isolate CPV-4 and
      from other ophioviruses. The three RNAs of P-121 had similar size and identical
      organization as those of CPV-4. The 24K and the RdRp proteins were potentially
      encoded in the viral complementary (vc) strand of RNA 1, the 54K protein
      potentially encoded in vcRNA 2 and the coat protein encoded in vcRNA 3. These
      four proteins from P-121 and CPV-4 had 87, 92, 93 and 94% amino acid identity,
      respectively, but only 22, 38, 25 and 33% identity with their homologous proteins
      from Mirafiori lettuce big vein virus (MLBVV), the only other ophiovirus
      completely sequenced. Biological and genetic differences between CPsV and MLBVV
      (and the other ophioviruses), would support their future allocation in different
      genera within a tentative family Ophioviridae.

PMID- 15449145
TI  - Cross-reactivity among sapovirus recombinant capsid proteins.
AB  - Sapovirus (SaV), a member of the genus Sapovirus in the family Caliciviridae, is
      an agent of human and porcine gastroenteritis. SaV strains are divided into five
      genogroups (GI-GV) based on their capsid (VP1) sequences. Human SaV strains are
      noncultivable, but expression of the recombinant capsid protein (rVP1) in a
      baculovirus expression system results in the self-assembly of virus-like
      particles (VLPs) that are morphologically similar to native SaV. In this study,
      rVP1 constructs of SaV GI, GII, and GV strains were expressed in a baculovirus
      expression system. The structures of the GI, GII, and GV VLPs, with diameters of
      41-48 nm, were morphologically similar to those of native SaV. However a fraction
      of GV VLPs were smaller, with diameters of 26-31 nm and spikes on the outline.
      This is the first report of GII and GV VLP formation and the first identification
      of small VLPs. To examine the cross-reactivities among GI, GII, and GV rVP1,
      hyperimmune rabbit antisera were raised against Escherichia coli-expressed GI,
      GII, and GV N- and C-terminal VP1. Western blotting showed the GI antisera cross
      reacted with GV rVP1 but not GII rVP1; GII antisera cross-reacted weakly with GI
      rVP1 but did not cross-react with GV rVP1; and GV antisera reacted only with GV
      rVP1. Also, hyperimmune rabbit and guinea pig antisera raised against purified GI
      VLPs were used to examine the cross-reactivities among GI, GII, and GV VLPs by an
      antigen enzyme-linked immunosorbent assay (ELISA). The ELISA showed that the GI
      VLPs were antigenically distinct from GII and GV VLPs.

PMID- 15449146
TI  - Fast method for longitudinal relaxation time and water content mapping of the
      human brain on a clinical MR scanner.
AB  - BACKGROUND: Longitudinal relaxation time (T(1)) map generation from human brain
      slices renders possible the in vivo follow-up of the changes in T(1) values
      during the course of several pathologies such as stroke, multiple sclerosis,
      traumatic brain injury etc. T(1) values can be converted to water contents, thus
      brain oedema reducing therapy can be non-invasively evaluated. The purpose of the
      study was to work out a fast and simple MRI method to obtain T(1) and water maps
      of the human brain. METHOD: The T(1) values of Gadolinium solutions with
      different concentrations were determined by means of MRI methods at a clinical MR
      scanner operating at 1 Tesla. In order to validate these measurements, T(1)
      values of the same Gadolinium solutions were also quantified with a relaxometer
      operating at the same field strength. T(1) and water maps from the brains of
      healthy volunteers were obtained with an inversion prepared spoiled gradient echo
      sequence (turbo-FLASH). FINDINGS: The T(1) values of Gadolinium solutions
      measured with the relaxometer showed a strong correlation (r > 0.999) with those
      determined with MRI sequences on the whole body scanner. The fastest MRI method
      to produce T(1) and consequent water maps from human brain was the inversion
      prepared turbo-FLASH sequence. CONCLUSIONS: The implemented turbo-FLASH method
      can produce T(1) and water map of a single virtual brain slice within 2 minutes.
      However, brain tissue containing haemorrhage should be excluded from the
      measurement due to the large influence of excessive haemoglobin concentration on
      longitudinal relaxation. The proposed method is available on most of the MR
      scanners, thus T(1) and water mapping of human brain can be routinely performed.

PMID- 15449147
TI  - Current status of pulmonary embolism in general surgery in Japan.
AB  - The true incidence of pulmonary embolism (PE) after general surgery in Japan is
      unknown. We searched the PubMed and Japana Centra Revuo Medicina 1985-2002
      databases, entering "surgery" and "pulmonary embolism" or "thromboembolism", and
      reviewed the reported incidence of clinical PE associated with general surgery in
      Japan. The overall incidence of PE after general surgery was 0.33%. Fatal PE was
      reported in 0.08% of the surgical population and the mortality rate of patients
      with PE was 31%. The incidence of PE after cancer surgery ranged from 0.57% after
      colon malignancy to 3.85% after pancreatic cancer surgery, and was significantly
      higher than that after surgery for noncancerous conditions (0.20%). The incidence
      of PE after various cancer operations corresponded to a moderate or high risk, as
      defined by the 6th American College of Chest Physicians consensus
      recommendations. There was no significant difference in the incidence of PE after
      laparoscopic and open abdominal surgery. The incidence of PE was four to six
      times lower in patients who had received mechanical prophylaxis, although the
      difference was not significant. In conclusion, the incidence of PE in Japanese
      surgical patients is not as low as previously thought. Perioperative prophylaxis
      against venous thromboembolism is important, but its benefits need to be
      confirmed by prospective clinical studies.

PMID- 15449148
TI  - Correlation of glomerular permeability, endothelial injury, and postoperative
      multiple organ dysfunction.
AB  - PURPOSE: To determine whether the degree of microalbuminuria correlates with the
      extent of endothelial cell injury, the severity of illness, and the magnitude of
      multiple organ dysfunction in patients who undergo emergency surgery. METHODS: We
      measured the urinary albumin : creatinine ratio (ACR) within 24 h after surgery
      in 31 patients and examined its relationship with various clinical measurements.
      RESULTS: The ACR increased during the first 24 h postoperatively. The log ACR
      correlated with the serum thrombomodulin concentration measured on the same day,
      but not with the level of plasma von Willebrand factor antigen. The increase in
      the log ACR correlated with the acute physiology and chronic health evaluation
      score (APACHE III), the simplified acute physiology score, the multiple organ
      dysfunction score, and the score of sequential organ failure assessment (SOFA)
      calculated on the same day, and the blood volume lost during the operation. The
      log ACR did not correlate with the white blood cell count or the serum C-reactive
      protein measured at the same time. The log ACR correlated with SOFA on
      postoperative days 3, 7, and 10, and mortality increased in accordance with the
      increase in log ACR. CONCLUSIONS: The urinary ACR correlated with the extent of
      endothelial cell injury, the severity of illness, and the magnitude of multiple
      organ dysfunction.

PMID- 15449149
TI  - Bilateral pneumothorax: a retrospective analysis of 40 patients.
AB  - PURPOSE: To retrospectively investigate the effectiveness of tube drainage in the
      treatment of bilateral pneumothorax. METHODS: We retrospectively examined 40
      patients with bilateral pneumothorax treated at the Thoracic and Cardiovascular
      Surgery Departments of Selcuk University between January 1994 and December 2000.
      There were 37 male and 3 female patients, aged 5-80 years (mean age, 42 years).
      The definite diagnosis of pneumothorax was made by radiological evaluation. In
      total, 38 tube drainage, 2 thoracentesis, and observation procedures were done,
      and some patients also required thoracotomy or median sternotomy. RESULTS: The
      types of pneumothorax were spontaneous in 9 patients, traumatic in 30, and
      iatrogenic in 1. We treated simultaneous bilateral pneumothorax in 34 patients
      and nonsimultaneous bilateral pneumothorax in 6 patients by tube drainage or
      additional surgical treatment. Two patients died. CONCLUSIONS: Bilateral
      pneumothorax may require extended hospital stay and could result in death. We
      think that tube drainage is appropriate and effective for most cases of bilateral
      pneumothorax.

PMID- 15449150
TI  - Enhanced induction of apoptosis in lung adenocarcinoma after preoperative
      chemotherapy with tegafur and uracil (UFT).
AB  - PURPOSE: To determine if the preoperative administration of tegafur and uracil
      (UFT) to patients with lung adenocarcinoma could induce apoptosis. METHODS: We
      conducted a randomized prospective study on 30 patients with lung adenocarcinoma,
      divided into two groups of 15 patients each. One group received UFT 600 mg/day
      preoperatively for 7 consecutive days and a control group received no
      chemotherapy or radiotherapy. The apoptotic index (AI) was determined by the
      terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin
      nick end-labeling (TUNEL) method. Expression of Ki-67 was examined by
      immunohistochemical staining. The concentration of 5-fluorouracil (5-FU) in tumor
      tissue was measured by chemical assay. RESULTS: The AI of lung adenocarcinoma
      cells increased significantly in the UFT-treated group but not in the control
      group. A significant positive correlation was seen between the AI and the 5-FU
      concentrations in the tumor tissue. CONCLUSIONS: The continuous oral
      administration of UFT for 7 days preoperatively resulted in enhanced apoptosis
      and a significant positive correlation between the AI and 5-FU concentrations in
      lung adenocarcinoma. Therefore, it may be possible to evaluate the effects of
      adjuvant chemotherapy based on the AI.

PMID- 15449151
TI  - Screening cost for abdominal aortic aneurysms: Japan-based estimates.
AB  - PURPOSE: The aim of this study was to evaluate the screening procedures in Japan
      economically focusing on the screening costs and the hospital costs for abdominal
      aortic aneurysm (AAA) surgery. METHODS: A total of 10,057 residents, 60 years of
      age or older, including 4 247 men and 5 810 women, participated in the screening
      test for AAA using ultrasound. RESULTS: Aneurysms were detected in 34
      participants, including 32 men and 2 women. The detection rate of AAA was 0.8% in
      men, 0.03% in women, and 0.3% in total. It cost 8 US dollars to screen each
      participant, and the cost to detect each aneurysm was thus estimated at 1,250
      dollars in men, 23,240 dollars in women, and 2,366 dollars in total. The
      difference in the mean hospital cost between ruptured and nonruptured AAA was
      21,833 dollars in our recent cases. Obesity, male sex, and smoking habits were
      all significant risk factors for AAA. CONCLUSION: Screening for AAA using
      ultrasound is useful not only for the early detection of AAA but also for a
      reduction in the overall medical cost.

PMID- 15449152
TI  - Limb ischemia and reperfusion during abdominal aortic aneurysm surgery.
AB  - PURPOSE: Abdominal aortic aneurysm (AAA) surgery involves ischemia and
      reperfusion of the lower extremities, but assessing the pathophysiological
      changes is difficult. We evaluated the extent and time course of ischemia
      reperfusion injury of the lower extremities during AAA surgery. METHODS: To
      monitor oxygen metabolism, two near-infrared spectroscopy (NIRS) probes were
      positioned on each calf muscle of nine patients undergoing AAA surgery. Lactate
      and pH were also measured in both iliac veins. RESULTS: Near-infrared
      spectroscopy signals responded sensitively to aortic cross-clamping and
      declamping. Lactate increased gradually and exponentially during aortic cross
      clamping, and reconstruction of the first iliac artery resulted in a further but
      transient increase in ipsilateral venous lactate. The time course of the pH level
      after declamping was almost a mirror image of that of lactate. Reconstruction of
      the first iliac artery did not affect the contralateral NIRS signals, lactate, or
      pH. CONCLUSIONS: Near-infrared spectroscopy may be useful for monitoring limb
      ischemia during AAA surgery. The transient increase in lactate and the transient
      decrease in pH after first declamping may contribute to the mechanism of
      declamping shock. The fact that first declamping did not affect measurements on
      the other side shows that contralateral ischemia progresses steadily after
      reconstruction of the first iliac artery. Therefore, reconstruction of the second
      iliac artery should be done as soon as possible.

PMID- 15449153
TI  - Minilaparotomy abdominal aortic aneurysm repair versus the retroperitoneal
      approach and standard open surgery.
AB  - PURPOSE: We evaluated the surgical results of minilaparotomy abdominal aortic
      aneurysm (AAA) repair in comparison with those of standard open repair and
      retroperitoneal approach repair. METHODS: Between February 2000 and January 2003,
      30 patients with AAA underwent minimal incision laparotomy repair (MINI) through
      an abdominal incision 7-12 cm long. Their clinical characteristics and in
      hospital outcome were then compared with those of patients who had undergone
      repair of AAA by a standard open technique (OPEN) or retroperitoneal approach
      technique (RETRO). RESULTS: There were significant differences between the MINI,
      OPEN, and RETRO groups in the time until the patient was able to resume eating
      (2.4 +/- 1.0 vs 4.4 +/- 2.4* vs 2.8 +/- 1.9 postoperative days [PODs],
      respectively; *P < 0.05), the time until ambulation outside the room (2.1 +/- 0.7
      vs 3.5 +/- 1.3* vs 2.5 +/- 1.9 PODs, respectively; *P < 0.05), and the operation
      times (188 +/- 43* vs 256 +/- 77 vs 238 +/- 59 min, respectively; *P < 0.05).
      CONCLUSION: Minilaparotomy repair is a feasible technique, which combines the
      benefits of a small incision with those of conventional open repair. With the
      exception of patients with an iliac artery aneurysm extending to the external or
      internal iliac artery, MINI repair should be considered for the elective
      treatment of patients with aortic disease.

PMID- 15449154
TI  - Previous or occult hepatitis B virus infection in hepatitis B surface antigen
      negative and anti-hepatitis C-negative patients with hepatocellular carcinoma.
AB  - PURPOSE: We investigated the clinical and virologic findings in hepatitis B
      surface antigen (HBsAg)-negative and anti-hepatitis C virus antibody (anti-HCV)
      negative patients with hepatocellular carcinoma (HCC) to investigate the role of
      previous or occult hepatitis B virus (HBV) infections in the development of HCC.
      METHODS: We examined sera and HCC samples from 40 HBsAg-negative and anti-HCV
      negative patients. Sera were tested for some viral markers, and genomic DNA was
      extracted from the HCC samples. HBx RNA was also extracted from the HCC and
      amplified by a polymerase chain reaction with reverse transcription (RT-PCR).
      RESULTS: Hepatocellular carcinomas from five patients with anti-HBc (group 1, 25
      patients) and nine patients without anti-HBc (group 2, 15 patients) were examined
      for HBx RNA. HBx RNA was detected in four of the five HCC samples from group 1
      and in four of the nine HCC samples from group 2. CONCLUSION: These findings
      suggested that previous or occult hepatitis B virus infection is common in HBsAg
      negative and anti-HCV-negative patients with HCC.

PMID- 15449155
TI  - Near-infrared spectroscopy with treadmill exercise to assess lower limb ischemia
      in patients with atherosclerotic occlusive disease.
AB  - PURPOSE: We used near-infrared spectroscopy (NIRS) to measure exercise-induced
      ischemia in patients with intermittent claudication, and compared these results
      with those obtained by ankle-brachial pressure index (ABPI) analysis. METHODS:
      Sixty-two patients with intermittent claudication caused by atherosclerotic
      occlusive disease exercised on a treadmill until reaching the maximal tolerated
      walking distance. We measured the ABPI at rest and after exercise until it
      returned to the baseline value. A NIRS probe was positioned on the patient's
      calf, which allowed the continuous monitoring of oxygen saturation (StO2),
      oxygenated hemoglobin (Oxy Hb), and deoxygenated hemoglobin (Deoxy Hb) in the
      calf muscles before, during, and after exercise. During exercise, the StO2 and
      Oxy Hb decreased, and the Deoxy Hb increased. The time taken for each measurement
      to return to the baseline value was defined as the recovery time. The recovery
      times obtained by NIRS and ABPI were compared. RESULTS: The recovery time for
      ABPI correlated well with that for StO(2 (rhos = 0.73), Oxy Hb (rhos = 0.63), and
      Deoxy Hb (rhos = 0.65); however, the recovery times measured by NIRS were shorter
      than the recovery time for the ABPI. CONCLUSIONS: Near-infrared spectroscopy is a
      reliable method for monitoring peripheral circulation during and after exercise,
      although the data generated provided slightly different information than the
      results obtained by ABPI.

PMID- 15449156
TI  - Oral administration of uracil-tegafur (UFT) inhibits liver micrometastasis of
      human colon cancer in an orthotopic nude mouse model and its early detection
      system.
AB  - PURPOSE: To evaluate the effect of UFT (an oral antineoplastic drug combining
      uracil and tegafur) as an adjuvant chemotherapy. METHODS: We examined whether UFT
      inhibits micrometastasis of the liver from colon cancer implanted into the cecum
      of nude mice in an orthotopic model. Moreover, we studied whether our early
      detection system using a polymerase chain reaction (PCR) of the human beta-globin
      gene would be useful in this model. RESULTS: The administration of 20 mg/kg UFT
      p.o., which is a relatively small dose compared with 65 mg/kg of the maximum
      tolerated dose of this drug in mice, inhibited liver metastasis completely when
      started immediately after a cecectomy (micrometastasis present at this time), but
      did not inhibit liver metastasis significantly when started at 4 weeks after a
      cecectomy (gross tumor present at this time). There were no severe toxicities at
      this dose. In our PCR study, all livers in 10 mice to which therapy was given
      immediately after a cecectomy and without liver metastasis showed no PCR
      amplified fragment, while 7 of 10 livers in the nontreatment group in which gross
      liver metastases were not observed demonstrated this fragment. CONCLUSIONS: These
      findings indicate that UFT is useful for either adjuvant chemotherapy or the
      inhibition of micrometastasis, and our system to detect micrometastasis by
      examining the human beta-globin gene is useful for the early evaluation of the
      efficacy of these drugs.

PMID- 15449157
TI  - Spiral tacks may contribute to intra-abdominal adhesion formation.
AB  - PURPOSE: With the inception of laparoscopic ventral hernia repair came a novel
      device not used in conventional hernia repair; the spiral tack. We conducted an
      experimental study on pigs to determine whether spiral tacks contribute to
      adhesion formation. METHODS: Using a standard laparoscopic technique in pigs,
      pieces of polypropylene mesh were fixed to the fascia on the upper abdominal
      wall, with polypropylene sutures on a randomly chosen side (side 1), and with 5
      mm spiral tacks on the opposite side (side 2). The extent, type, and tenacity of
      the adhesions were assessed on postoperative days (PODs) 30 and 90. RESULTS: The
      mesh fixed to the abdominal wall with spiral tacks tended to increase the extent,
      type, and tenacity of adhesions more than the mesh fixed with polypropylene
      sutures (P < 0.05). CONCLUSIONS: Spiral tacks contributed to the formation of
      adhesions more than polypropylene mesh did. Although this was a small-scale
      animal study, our findings suggest that the effect of spiral tacks used in
      laparoscopic ventral hernia repair should be assessed and the consequences
      monitored more closely.

PMID- 15449158
TI  - Effect of chymase-dependent transforming growth factor beta on peritoneal
      adhesion formation in a rat model.
AB  - PURPOSE: To clarify the role of chymase produced from mast cells, which are
      closely related to adhesion formation, we investigated the preventive effect of a
      chymase inhibitor on adhesion formation in a rat model. METHODS: A lesion was
      created in rats by uterus scraping, and a chymase inhibitor, Suc-Val-Pro
      Phep(OPh)2 (10 microM), or a placebo was injected into the abdomen. The level of
      transforming growth factor beta (TGF-beta) in the peritoneal fluid was also
      measured. RESULTS: By 2 weeks after the operation, the scores for adhesion
      formation in the chymase inhibitor-treated group were significantly lower than
      those in the placebo-treated group, at 1.64 +/- 0.34 and 3.27 +/- 0.19,
      respectively (P < 0.01). After scraping the uterus, the level of TGF-beta in the
      peritoneal fluid was significantly higher in the placebo-treated group, whereas
      it was significantly suppressed by the chymase inhibitor. CONCLUSIONS: Chymase
      may play an important role in adhesion formation aided by TGF-beta.

PMID- 15449159
TI  - Esophageal replacement using a reversed gastric tube for lye stricture in a
      child: report of a case.
AB  - A 5-year-old girl ingested lye, a detergent used in electric dishwashers. She was
      transferred to our hospital after balloon dilatation, performed for stenosis
      resulting from corrosive esophagitis, was complicated by esophageal perforation
      causing mediastinitis. Although the mediastinitis resolved with conservative
      treatment, the stenosis did not improve. Therefore, we performed esophageal
      replacement using a reversed gastric tube, which successfully relieved the
      obstruction, although she still had slight gastroesophageal reflux 6 months
      postoperatively.

PMID- 15449160
TI  - Massive hemorrhage and pseudo-obstruction of the small intestine caused by
      primary AL amyloidosis associated with gastric cancer: report of a case.
AB  - We report a case of AL amyloidosis in a patient diagnosed with early gastric
      cancer after presenting with massive gastrointestinal hemorrhage and pseudo
      obstruction of the small intestine. Primary systemic amyloidosis accounts for 7%
      of nonhematological malignancies, but very few cases of gastric carcinoma in
      patients with primary amyloidosis have been described. We performed distal
      gastrectomy with biopsy of the small intestine in the absence of a diagnosis of
      systemic amyloidosis associated with early gastric cancer; however, the patient
      suffered severe postoperative complications secondary to the amyloidosis.
      Although acute pseudo-obstruction is an uncommon clinical manifestation of AL
      amyloidosis, the coexistence of both gastrointestinal hemorrhage and pseudo
      obstruction of the small intestine should alert the clinician to a diagnosis of
      gastrointestinal amyloidosis. We discuss the clinical manifestations of primary
      amyloidosis occurring in association with gastric cancer.

PMID- 15449161
TI  - Transverse to descending colon volvulus and megacolon with mesenterium commune:
      report of a case.
AB  - We report a case of volvulus of the transverse-descending (T-D) colon and
      megacolon associated with mesenterium commune. A 70-year-old man was referred to
      our hospital for investigation of severe constipation and abdominal fullness. On
      physical examination, his abdomen was remarkably distended with generalized
      tenderness, and weak bowel sounds. Abdominal X-ray showed megacolon at the
      splenic flexure and a contrast medium enema study showed tapering of the upper
      rectum. Accordingly, under a diagnosis of T-D colon volvulus, we performed an
      emergency operation to release the colon volvulus. The intraoperative findings
      showed a volvulus of the T-D colon with mesenterium commune. The patient
      recovered uneventfully and his symptoms resolved; however, a postoperative barium
      enema showed residual megacolon at the splenic flexure.

PMID- 15449162
TI  - Laparoscopic spleen-preserving pancreatic tail resection for an intrapancreatic
      accessory spleen mimicking a nonfunctioning endocrine tumor: report of a case.
AB  - Laparoscopic surgery is now performed for several pancreatic disorders, such as
      benign tumors of the pancreatic body or tail, which are a good indication for
      laparoscopic resection. However, the risk of pancreatic fistula after distal
      pancreatectomy, performed laparoscopically or by open surgery, is a topic of
      debate. We report the case of a 61-year-old man in whom a routine follow-up
      computed tomography (CT) scan showed a solid, well-defined mass, 1.5 cm in
      diameter, in the pancreatic tail. The mass was homogeneously enhanced from the
      early phase to the super-delayed phase on enhanced CT. We suspected a
      nonfunctioning endocrine tumor of the pancreas, and surgery was performed
      laparoscopically. After dissecting the pancreatic tail away from the splenic
      hilum and the splenic vessels, it was resected using only a linear stapler. The
      histological diagnosis was an intrapancreatic accessory spleen. The patient was
      discharged on postoperative day 14, but was readmitted 6 days later because of a
      pancreatic fistula, which was treated by CT-guided percutaneous drainage.

PMID- 15449163
TI  - Endo-bowel clamp (PL540S) for safe rectal irrigation in laparoscopy-assisted
      rectal resection.
AB  - We describe a technique of rectal irrigation using an endo-bowel clamp (PL540S)
      in laparoscopy-assisted rectal resection. One of the major concerns associated
      with current techniques of laparoscopy-assisted rectal resection is accidental
      tumor spillage because it is difficult to perform the necessary procedures
      without grasping and manipulating the bowel and mesorectum near the tumor.
      Therefore, sufficient intraoperative rectal irrigation is essential for
      preventing intraluminal implantation of rectal cancer. However, this can be
      difficult, especially if the tumor is located in the rectum. By placing a PL540S
      before transection, it is possible to occlude the rectum completely and irrigate
      it effectively. We think that the PL540S is a valuable device in laparoscopic
      surgery for rectal cancer.

PMID- 15449164
TI  - On the connection between hard cosmic ray flux variations and changes in
      cardiovascular disease in Vilnius city.
AB  - A predictive correlation between hard cosmic ray flux (HCRF) near the Earth's
      surface and sudden increases in the number of cases of cardiovascular disease
      (CVD) was studied in Vilnius city. Gamma spectrometers were used to measure HCRF.
      Changes in the total number of impulses registered by these devices were taken as
      the physical parameter for prediction of an increase in the number of CVD cases.
      For quantitative assessment of CVD dynamics two empirical criteria for HCRF were
      proposed: (1) a consistent fall in the HCRF by 200 or more impulses for 4 or more
      hours per day; (2) the difference (no less than 15 impulses per hour) between the
      average number of impulses registered in 2 (subsequent and previous) days. The
      periods analyzed were those when the number of CVD cases exceeded the average
      monthly level by 10% and 15%. HCRF fluctuations were used as an indirect
      indicator of variations in the geomagnetic field, and a leap in CVD cases was
      predicted 1-3 days following a change in the HCRF according to the two criteria
      mentioned above. The predictive reliability of an increase in CVD cases within 2
      3 days exceeded 80%, and within 1-2 days 70%. No essential difference in
      predictive reliability was observed when the number of CVD cases exceeded the
      average monthly level by 10% or 15%. Geomagnetic field variations contribute only
      insignificantly to leaps in the number of CVD cases, which are evoked by the sum
      effects of other factors. The results of the present study should be regarded as
      preliminary.

PMID- 15449165
TI  - [The future of headaches].

PMID- 15449166
TI  - [Headache attacks with ipsilateral autonomic symptoms].
AB  - Following the new IHS-classification, cluster headache, paroxysmal hemicrania and
      SUNCT syndrome are included into the classification as trigemino-autonomic
      cephalgias (TAC's). Clinically, they share strictly halfsided head pain with
      autonomic symptoms. The headaches often occur during particular sleep stages and
      are associated with other chronobiologic factors. Broadly the management of TAC's
      comprises acute and prophylactic treatment. Paroxysmal hemicrania and hemicrana
      continua have a very robust response to indomethacin. Acute cluster headache
      attacks can be treated with inhalation of oxygen or serotonin agonists, whereas
      verapamil is the drug of choice in the prophylactic treatment. This review covers
      the clinical picture and therapeutic options. Allthough studies following the
      criteria of evidence based medicine (EBM) are rare, most patients can be treated
      sufficiently.

PMID- 15449167
TI  - [Therapy of chronic pain with lidocaine plasters].

PMID- 15449169
TI  - Poststreptococcal glomerulonephritis with pulmonary edema presenting as
      respiratory distress.
AB  - Acute poststreptococcal glomerulonephritis(PSGN) is characterized by an abrupt
      onset of edema,hypertension, and hematuria. Although the association of pulmonary
      edema with acute glomerulonephritis has been established, it is uncommon for
      children with PSGN to present with respiratory distress due to pulmonary edema.
      We encountered six such patients, aged 6-10 years, during a 10-month period. The
      demographic data, clinical manifestations, laboratory data, radiographic
      pictures, and clinical courses were collected. All patients presented to the
      primary pediatricians with dyspnea and alveolar infiltrates with bilateral
      pleural effusions on plain chest radiographs that were misinterpreted as
      pneumonia initially. The diagnosis of PSGN was de-layed until the awareness of
      the presence of pulmonary edema complicating PSGN. Subsequent urinalysis and
      blood pressure measurement all showed microscopic hematuria and hypertension.
      Elevated serum antistreptolysin 0 titers and depressed serum complement C3 levels
      confirmed the diagnosis of PSGN. Two patients progressed to respiratory failure
      because of a delayed diagnosis of PSGN. All patients recovered without sequelae
      following appropriate diuresis and antihypertensive therapy. We conclude that in
      preschool and school-age children who present with dyspneic respirations and a
      chest radiograph showing radiographic features of pulmonary edema, proper
      evaluation including blood pressure recording and urinalysis should be performed
      immediately. Prompt diagnosis and early therapy of PSGNmay avoid mortality and
      unnecessary therapeutic intervention.

PMID- 15449170
TI  - Effects of advanced glycosylation endproducts on perlecan core protein of
      glomerular epithelium.
AB  - Perlecan is one of major heparan sulfate proteoglycans in the glomerular basement
      membrane and is reduced in the renal parenchyma of diabetic patients and animals
      with proteinuria. To examine the effects of glucose and advanced glycosylated end
      products (AGE) on perlecan, we cultured rat glomerular epithelial cells (GEpC) on
      AGE- or bovine serum albumin (BSA)-coated plates under normal (NG, 5 mM) and high
      glucose (HG, 30 mM) conditions and measured the change in perlecan core protein
      production by a sandwich ELISA and northern blot analysis. We observed
      significant decreases of perlecan core protein under HG conditions at 1 week
      incubation, specifically on the AGE-coated compared with the BSA-coated surface,
      by 22.2% and 4.7%, respectively. The expression of mRNA for perlecan promoter was
      decreased under HG conditions on AGE-coated surfaces by 19.7% at 2 days and 61.1%
      at 1 week. Even under NG condition, the expression of mRNA was reduced by 30% at
      1 week if GEpC were grown on an AGE-coated surface. In conclusion, HG and AGE
      have an additive effect in reducing the production of perlecan core protein by
      GEpC in vitro. AGE had a greater effect than HG, implying that the inhibition of
      AGE formation may be more effective than short-term glucose control in the
      prevention of diabetic proteinuria.

PMID- 15449171
TI  - A proteomic fingerprint of dissolved organic carbon and of soil particles.
AB  - Mass spectrometry-based proteomics was applied to analyze proteins isolated from
      dissolved organic matter (DOM). The focal question was to identify the type and
      biological origin of proteins in DOM, and to describe diversity of protein origin
      at the level of higher taxonomic units, as well as to detect extracellular
      enzymes possibly important in the carbon cycle. Identified proteins were
      classified according to their phylogenetic origin and metabolic function using
      the National Center for Biotechnology Information (NCBI) protein and taxonomy
      database. Seventy-eight percent of the proteins in DOM from the lake but less
      than 50% in forest soil DOM originated from bacteria. In a deciduous forest, the
      number of identified proteins decreased from 75 to 28 with increasing soil depth
      and decreasing total soil organic carbon content. The number of identified
      proteins and taxonomic groups was 50% higher in winter than in summer. In spruce
      forest, number of proteins and taxonomic groups decreased by 50% on a plot where
      trees had been girdled a year before and carbohydrate transport to roots was
      terminated. After girdling, proteins from four taxonomic groups remained as
      compared to nine taxonomic groups in healthy forest. Enzymes involved in
      degradation of organic matter were not identified in free soil DOM. However,
      cellulases and laccases were found among proteins extracted from soil particles,
      indicating that degradation of soil organic matter takes place in biofilms on
      particle surfaces. These results demonstrate a novel application of proteomics to
      obtain a "proteomic fingerprint" of presence and activity of organisms in an
      ecosystem.

PMID- 15449172
TI  - The human T locus and spina bifida risk.
AB  - The transcription factor T is essential for mesoderm formation and axial
      development during embryogenesis. Embryonic genotype for a single-nucleotide
      polymorphism in intron 7 of T ( TIVS7 T/C) has been associated with the risk of
      spina bifida in some but not all studies. We developed a novel genotyping assay
      for the TIVS7 polymorphism using heteroduplex generator methodology. This assay
      was used to genotype spina bifida case-parent trios and the resulting data were
      analyzed using the transmission disequilibrium test and log-linear analyses.
      Analyses of these data demonstrated that heterozygous parents transmit the TIVS7
      C allele to their offspring with spina bifida significantly more frequently than
      expected under the assumption of Mendelian inheritance (63 vs 50%, P=0.02).
      Moreover, these analyses suggest that the TIVS7-C allele acts in a dominant
      fashion, such that individuals carrying one or more copies of this allele have a
      1.6-fold increased risk of spina bifida compared with individuals with zero
      copies. In silico analysis of the sequence surrounding this polymorphism revealed
      a potential target site for olfactory neuron-specific factor-1, a transcription
      factor expressed in the neural tube during development, spanning the polymorphic
      site. Several other putative, developmentally important and/or environmentally
      responsive transcription factor-binding sites were also identified close to the
      TIVS7 polymorphism. The TIVS7 polymorphism or a variant that is in linkage
      disequilibrium with the TIVS7 polymorphism may, therefore, play a role in T gene
      expression and influence the risk of spina bifida.

PMID- 15449173
TI  - Mutational analysis of OGG1, MYH, MTH1 in FAP, HNPCC and sporadic colorectal
      cancer patients: R154H OGG1 polymorphism is associated with sporadic colorectal
      cancer patients.
AB  - MYH, OGG1 and MTH1 are members of base excision repair (BER) families, and MYH
      germline mutations were recently identified in patients with multiple adenomas or
      familial adenomatous polyposis (FAP). A total of 20 APC-negative Korean FAP
      patients were analyzed for OGG1, MYH and MTH1 germline mutations. A total of 19
      hereditary nonpolyposis colorectal cancer (HNPCC), 86 suspected HNPCC, and 246
      sporadic colorectal cancer cases were investigated for OGG1 and MYH mutations. A
      total of 14 R154H OGG1 polymorphisms were identified in hereditary, sporadic
      colorectal cancers, and normal controls. For the case-control analysis of OGG1
      R154H, a total of 625 hereditary or sporadic colorectal cancer patients and 527
      normal controls were screened. R154H was a rare polymorphism associated with
      sporadic colorectal cancer patents (OR: 3.586, P= 0.053). R154H does not
      segregate with cancer phenotypes. Upon examining the possibility of recessive
      inheritance of R154H, we could not identify any complementary mutations in OGG1,
      MYH or MTH1. Samples with R154H were further screened for mutations of K-ras,
      beta-catenin, APC, p53, BRAF and the microsatellite instability (MSI) status.
      Eight somatic mutations were identified in these genes and G:C to T:A
      transversion mutations were not dominant in samples harboring R154H. This result
      raises the possibility that OGG1 R154H may function as a low/moderate-penetrance
      modifier for colorectal cancer development.

PMID- 15449174
TI  - Genome-scan analysis for quantitative trait loci in an F2 tilapia hybrid.
AB  - We searched for genetic linkage between DNA markers and quantitative trait loci
      (QTLs) for innate immunity, response to stress, biochemical parameters of blood,
      and fish size in an F2 population derived from an interspecific tilapia hybrid
      (Oreochromis mossambicusx O. aureus). A family of 114 fish was scanned for 40
      polymorphic microsatellite DNA markers and two polymorphic genes, covering
      approximately 80% of the tilapia genome. These fish had previously been
      phenotyped for seven immune-response traits and six blood parameters. Critical
      values for significance were P <0.05 with the false discovery rate (FDR)
      controlled at 40%. The genome-scan analysis resulted in 35 significant marker
      trait associations, involving 26 markers in 16 linkage groups. In a second
      experiment, nine markers were re-sampled in a second family of 79 fish of the
      same species hybrid. Seven markers (GM180, GM553, MHC-I, UNH848, UNH868, UNH898
      and UNH925) in five linkage groups (LG 1, 3, 4, 22 and 23) were associated with
      stress response traits. An additional six markers (GM47, GM552, UNH208, UNH881,
      UNH952, UNH998) in five linkage groups (LG 4, 16, 19, 20 and 23) were verified
      for their associations with immune response traits, by linkage to several
      different traits. The portion of variance explained by each QTL was 11% on
      average, with a maximum of 29%. The average additive effect of QTLs was 0.2
      standard deviation units of stress response traits and fish size, with a maximum
      of 0.33. In three linkage groups (LG 1, 3 and 23) markers were associated with
      stress response, body weight and sex determination, confirming the location of
      QTLs reported by several other studies.

PMID- 15449175
TI  - Complete DNA sequence of the linear mitochondrial genome of the pathogenic yeast
      Candida parapsilosis.
AB  - The complete sequence of the mitochondrial DNA of the opportunistic yeast
      pathogen Candida parapsilosis was determined. The mitochondrial genome is
      represented by linear DNA molecules terminating with tandem repeats of a 738-bp
      unit. The number of repeats varies, thus generating a population of linear DNA
      molecules that are heterogeneous in size. The length of the shortest molecules is
      30,922 bp, whereas the longer molecules have expanded terminal tandem arrays
      (nx738 bp). The mitochondrial genome is highly compact, with less than 8% of the
      sequence corresponding to non-coding intergenic spacers. In silico analysis
      predicted genes encoding fourteen protein subunits of complexes of the
      respiratory chain and ATP synthase, rRNAs of the large and small subunits of the
      mitochondrial ribosome, and twenty-four transfer RNAs. These genes are organized
      into two transcription units. In addition, six intronic ORFs coding for
      homologues of RNA maturase, reverse transcriptase and DNA endonucleases were
      identified. In contrast to its overall molecular architecture, the coding
      sequences of the linear mitochondrial DNA of C. parapsilosis are highly similar
      to their counterparts in the circular mitochondrial genome of its close relative
      C. albicans. The complete sequence has implications for both mitochondrial DNA
      replication and the evolution of linear DNA genomes.

PMID- 15449176
TI  - Mapping Ds insertions in barley using a sequence-based approach.
AB  - A transposon tagging system, based upon maize Ac/Ds elements, was developed in
      barley (Hordeum vulgaresubsp. vulgare). The long-term objective of this project
      is to identify a set of lines with Ds insertions dispersed throughout the genome
      as a comprehensive tool for gene discovery and reverse genetics. AcTPase and Ds
      bar elements were introduced into immature embryos of Golden Promise by biolistic
      transformation. Subsequent transposition and segregation of Ds away from AcTPase
      and the original site of integration resulted in new lines, each containing a
      stabilized Ds element in a new location. The sequence of the genomic DNA flanking
      the Ds elements was obtained by inverse PCR and TAIL-PCR. Using a sequence-based
      mapping strategy, we determined the genome locations of the Ds insertions in 19
      independent lines using primarily restriction digest-based assays of PCR
      amplified single nucleotide polymorphisms and PCR-based assays of insertions or
      deletions. The principal strategy was to identify and map sequence polymorphisms
      in the regions corresponding to the flanking DNA using the Oregon Wolfe Barley
      mapping population. The mapping results obtained by the sequence-based approach
      were confirmed by RFLP analyses in four of the lines. In addition, cloned DNA
      sequences corresponding to the flanking DNA were used to assign map locations to
      Morex-derived genomic BAC library inserts, thus integrating genetic and physical
      maps of barley. BLAST search results indicate that the majority of the transposed
      Ds elements are found within predicted or known coding sequences. Transposon
      tagging in barley using Ac/Ds thus promises to provide a useful tool for studies
      on the functional genomics of the Triticeae.

PMID- 15449177
TI  - Construction of DNA vaccines and their induced protective immunity against
      experimental Eimeria tenella infection.
AB  - In an attempt to construct a DNA vaccine against chicken coccidiosis, the TA4
      gene of Eimeria tenella strain BJ was ligated to the mammalian expression vector
      pcDNA3.1/Zeo(+) to give pcDNA3.1-TA4 (pcDT). Then, Et1A (E. tenella refractile
      body gene) was ligated to it, upstream, aiming to be expressed in fusion with
      TA4, giving pcDNA3.1-Et1A-TA4 (pcDET). The constructed DNA vaccines were given to
      broilers intramuscularly 10-15 min after the breasts had been pre-treated with
      25% sucrose solution. At 7 days after the second vaccination, chickens were
      challenged with 3 x 10(4) sporulated oocysts of E. tenella BJ. The chickens were
      killed and the lesion scores of the ceca, the relative body-weight gains and the
      numbers of oocysts in the ceca of each group of chickens were calculated at day 8
      post-inoculation. Results indicated that both pcDT and pcDET could induce
      protective immunity against coccidial challenge. Their use could obviously reduce
      oocyst output and alleviate chicken body-weight decrease due to coccidial
      infection. An anti-coccidial index of 160 was achieved with a treatment of 50
      microg pcDET and 100 microg pcDT.

PMID- 15449178
TI  - Association of matrix metalloproteinase-9 in eosinophilic meningitis of BALB/c
      mice caused by Angiostrongylus cantonensis.
AB  - Induction of gelatinase in eosinophilic meningitis of BALB/c-strain mice was
      caused by Angiostrongylus cantonensis. Time-course studies showed that the
      molecular weight of 94-kDa gelatinase was detected at day 10 post-inoculation
      (PI), and reached a high intensity from days 15 to 25 PI. The 94-kDa gelatinase
      activity was clearly inhibited by EDTA and 1,10-phenanthroline, but not by
      leupeptin and phenylmethanesulphonyl fluoride. When immunoblots were performed
      using specific antiserums against the 94-kDa gelatinase B (matrix
      metalloproteinase-9; MMP-9) with cerebrospinal fluid (CSF), the 94-kDa
      immunopositive band was MMP-9. Immunohistochemistry studies demonstrated MMP-9
      localisation within eosinophils and macrophages. The increased MMP-9 activity was
      closely associated with the rapid rise of CSF eosinophils, and the inflammatory
      reaction of the subarachnoid space. In contrast to changes in MMP-9, MMP-2
      activity was constitutive and unaffected in this parasitic meningitis. These
      results show that MMP-9 was associated with eosinophilic meningitis, and that the
      enzyme may be a useful marker for angiostrongyliasis meningitis.

PMID- 15449179
TI  - Effects of blockers of Ca2+ channels and other ion channels on in vitro
      excystment of Paragonimus ohirai metacercariae induced by sodium cholate.
AB  - The inhibitory effects of various ion channel blockers were examined on in vitro
      excystment of Paragonimus ohirai metacercariae induced by a bile salt, sodium
      cholate. At a concentration of 10 microM, bepridil, a non-selective Ca(2+)
      channel blocker, completely inhibited in vitro excystment, whereas TEA,
      lidocaine, and R(+)-IAA-94, channel blockers against K(+), Na(+) and Cl(-) ions,
      respectively, benzamil, an Na(+)/H(+) and Na(+)/Ca(2+) ion exchanger blocker, and
      R(+)-DIOA, a [K(+), Cl(-)] cotransporter inhibitor, did not. Considering the
      previous result that Ca(2+) ionophores are also efficient inducing factors for in
      vitro excystment of P. ohirai metacercariae and the present result, bile salts
      appear to induce the excystment of P. ohirai metacercariae through evoking the
      Ca(2+) channels of target cells within the metacercarial juveniles.

PMID- 15449180
TI  - Rapid detection of Wuchereria bancrofti in mosquitoes by LightCycler polymerase
      chain reaction and melting curve analysis.
AB  - A LightCycler real-time polymerase chain reaction (PCR) assay was developed to
      detect Wuchereria bancrofti DNA in blood-fed mosquitoes. The assay is based on
      fluorescence melting curve analysis of the PCR product generated from a family of
      repeated DNA elements: the 182 bp SspI repeat, specific to the genus Wuchereria.
      According to the melting temperature, W. bancrofti infected-mosquitoes were
      differentiated from Brugia malayi-infected and non-infected mosquitoes as well as
      from genomic DNA of Dirofilaria immitis and human DNA. The method proved to be
      100% sensitive in all W. bancrofti-infected mosquitoes. Melting curve analysis
      offers a rapid alternative for the specific detection of W. bancrofti in
      mosquitoes. It is very accurate and sensitive, allows a high throughput and can
      be performed on very small samples. The method therefore has great potential for
      application in epidemiological studies.

PMID- 15449181
TI  - Proteolytic activities in Trypanosoma rangeli and stercorarian trypanosomes:
      taxonomic implications.
AB  - We analysed the proteinase profiles in nine Trypanosoma (Herpetosoma) rangeli
      strains from distinct geographical regions, three T. (Schizotrypanum) cruzi
      reference strains and in T. (Herpetosoma) lewisi, T. (Herpetosoma) musculi and T.
      (Megatrypanum) conorhini samples by detection of enzyme activity on SDS-PAGE
      containing co-polymerized gelatin as substrate. Three different profiles of
      cysteine proteinase activity were detected in T. rangeli within a similar range
      of molecular mass. T. lewisi and T. musculi displayed a similar pattern of
      proteolysis, quite distinct from the ones detected in T. rangeli and in the other
      subgenera belonging to the stercorarian trypanosomes. Our results indicate the
      potential of the SDS-PAGE-gelatin technique in distinguishing between these
      parasites, and confirm several findings on the existence of subgroups within the
      T. rangeli taxon. These may represent either subspecies or distinct species. Our
      results also demonstrate the lack of affinity of T. rangeli with the species
      belonging to the subgenus Herpetosoma.

PMID- 15449182
TI  - High-level mRNA quantification of proliferation marker pKi-67 is correlated with
      favorable prognosis in colorectal carcinoma.
AB  - PURPOSE: The present study retrospectively examines the expression of pKi-67 mRNA
      and protein in colorectal carcinoma and their correlation to the outcome of
      patients. METHODS: Immunohistochemistry and quantitative RT-PCR were used to
      analyze the expression of pKi-67 in 43 archival specimens of patients with
      curatively resected primary colorectal carcinoma, who were not treated with neo
      adjuvant therapy. RESULTS: We determined a median pKi-67 (MIB-1) labeling index
      of 31.3% (range 10.3-66.4%), and a mean mRNA level of 0.1769 (DeltaC(T): range
      0.01-0.69); indices and levels did not correlate. High pKi-67 mRNA DeltaC(T)
      values were associated with a significantly favorable prognosis, while pKi-67
      labeling indices were not correlated to prognostic outcome. A multivariate
      analysis of clinical and biological factors indicated that tumor stage (UICC) and
      pKi-67 mRNA expression level were independent prognostic factors. CONCLUSION:
      Quantitatively determined pKi-67 mRNA can be a good and new prognostic indicator
      for primary resected colorectal carcinoma.

PMID- 15449183
TI  - A rationale for neoadjuvant systemic treatment followed by surgical assessment
      and intraperitoneal chemotherapy in patients presenting with non-surgically
      resectable ovarian or primary peritoneal cancers.
AB  - PURPOSE: Optimal management of patients with advanced ovarian or primary
      peritoneal cancers who have received, and achieved an excellent response to,
      neoadjuvant chemotherapy remains undefined. METHODS: Five patients are briefly
      presented who were found to have extensive intra-abdominal carcinomatosis from
      ovarian/peritoneal cancers and were initially treated with a
      carboplatin/paclitaxel-based neoadjuvant chemotherapy program. Following major
      objective and subjective responses each patient underwent a surgical re
      assessment and subsequently received single-agent intraperitoneal platinum
      (cisplatin or carboplatin). RESULTS AND CONCLUSION: In the absence of definitive
      data from randomized phase-3 trials defining optimal management in this setting,
      a rational argument can be provided supporting the use of this multi-modality
      management strategy (neoadjuvant chemotherapy followed by surgery and regional
      chemotherapy) in carefully selected patients presenting with extensive ovarian or
      primary peritoneal cancers.

PMID- 15449184
TI  - The benefit of bone-seeking radiopharmaceuticals in the treatment of metastatic
      bone pain.
AB  - PURPOSE: The surface bone-seeking radiopharmaceuticals rhenium-188-HEDP (188Re
      HEDP) and samarium-153-EDTMP (153Sm-EDTMP) were investigated to determine the
      efficacy and toxicity in pain palliation in bone metastases. METHOD: The effect
      of treatment with 188Re-HEDP and 153Sm-EDTMP on pain symptoms, life quality, and
      bone marrow function were obtained in 46 patients with prostate and breast
      cancer. There were 31 patients treated with 188Re-HEDP (3194+/-387 MBq) and 15
      patients with 153Sm-EDTMP (2940+/-545 MBq). The 188Re-HEDP group included 6
      patients and 25 patients, and the 153Sm-EDTMP group 6 patients and 9 patients
      with breast and prostate cancer, respectively. All patients had an interview
      using standardized sets of questions before and after therapy for 12 weeks. Blood
      counts were taken weekly for 6 weeks and after 12 weeks. RESULTS: After treatment
      with 188Re-HEDP, 77% of patients reported pain relief and 73% after 153Sm-EDTMP.
      Sixteen percent of the patients treated with 188Re-HEDP and 13% of those given
      153Sm-EDTMP could discontinue their analgesics and were pain free. Patients
      described an improvement on the Karnofsky performance scale from 73+/-7 to 85+/
      8% 12 weeks after 188Re-HEDP (p<0.05) and from 68+/-9 to 74+/-9% after 153Sm
      EDTMP (p=0.217). Only 3 patients post-188Re-HEDP and 2 patients post-153Sm-EDTMP
      showed a thrombocytopenia below 100 x 10(3)/microl. The maximum nadir of platelet
      and leukocyte counts were observed between the second to fourth week after
      treatment in both and was reversible within 12 weeks. There were no significant
      differences in pain palliation, Karnofsky performance scale and bone marrow
      toxicity between the lower beta energy 153Sm-EDTMP and the higher beta energy
      188Re-HEDP (p=0.098-0.442). CONCLUSION: Both radiopharmaceuticals were effective
      in pain palliation, without induction of severe side effects or significant
      differences in therapeutic efficacy or toxicity.

PMID- 15449185
TI  - A phase II trial of FUdR in patients with advanced pancreatic cancer.
AB  - PURPOSE: This phase II study was conducted to assess the efficacy of
      fluorodeoxyuridine (FUdR) in patients with metastatic, advanced pancreatic cancer
      who had no previous chemotherapy. PATIENTS AND METHODS: Twenty patients were
      enrolled in this single institution trial. The primary endpoint of this study was
      the assessment of overall survivorship. The secondary endpoints were to estimate
      the time to tumor progression and the assessment of toxicity in this cohort of
      patients. Treatment consisted of FUdR 150 mg/kg dissolved in 500 cc normal saline
      intravenous infusion over 24 h. Eight weeks of treatment constituted one course
      of chemotherapy. Tumor measurements were conducted at 8-weekly intervals.
      RESULTS: Four patients achieved partial response and 16 patients had stable
      disease. Median survival of patients treated with FUdR was 11.6 months with a
      range of 3-16 months. Median progression-free survival was 6 months. Overall,
      chemotherapy was well tolerated with low incidence of grade 3 or 4 toxicity.
      CONCLUSIONS: Systemic chemotherapy with high dose FUdR administered on a weekly
      schedule has led to encouraging survival outcomes and improved quality of life as
      compared to previous phase II single agent chemotherapeutic trials.

PMID- 15449186
TI  - Effects of the angiotensin-I converting enzyme inhibitor perindopril on tumor
      growth and angiogenesis in head and neck squamous cell carcinoma cells.
AB  - PURPOSE: Recently, it has been reported that angiotensin-I converting enzyme
      (ACE) inhibitors have anticancer activity. In particular, the ACE inhibitor,
      perindopril, significantly inhibits tumor growth and angiogenesis in
      hepatocellular carcinoma cells along with suppression of the VEGF level. However,
      the mechanisms of suppression of the VEGF level are still unclear, and there are
      no previous reports on this subject related to head and neck squamous cell
      carcinoma (HNSCC). In some previous studies, angiotensin II, which is produced
      from angiotensin I by ACE, directly stimulates VEGF expression. METHODS: In the
      present study, we focused upon angiotensin II, and investigated the effect of
      perindopril on VEGF expression, angiogenesis, and tumor development of HNSCC with
      in vitro and in vivo studies. RESULTS: In the in vitro cell proliferation assays,
      there was no significant difference between the perindopril-treated group and the
      control group. However, the perindoprilat-treated group showed a significant
      reduction in mRNA expression of VEGF and inhibited the induction activity of the
      VEGF promoter in comparison to the control group. Perindoprilat treatment also
      significantly suppressed angiotensin II production in vitro. In the in vivo
      studies, perindopril had a significant inhibitory effect on tumor growth, and
      reduced blood vessel formation surrounding the tumors. CONCLUSIONS: Our findings
      suggest that perindopril has no direct cytotoxicity against tumor cells, but has
      a potential to inhibit tumor growth due to suppression of VEGF-induced
      angiogenesis in vivo. Angiotensin II might have an important role in
      carcinogenesis, and the antiangiogenic activity of perindopril is at least partly
      mediated by angiotensin II inhibition. The ACE inhibitor perindopril has clinical
      potential as a useful antitumor agent.

PMID- 15449187
TI  - Methylenetetrahydrofolate reductase C677T polymorphism and predisposition towards
      esophageal squamous cell carcinoma in a German Caucasian and a northern Chinese
      population.
AB  - PURPOSE: Folate deficiency is considered to increase the risk of developing
      esophageal cancer. Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme
      involved in folate metabolism. A single C --> T substitution at nucleotide 677 of
      the MTHFR cDNA influences enzyme activity. The purpose of this study is to
      compare the association of the MTHFR C677T polymorphism with susceptibility to
      esophageal squamous cell carcinoma (ESCC). METHODS: Using real-time PCR and
      melting curve analysis, the MTHFR C677T genotypes were determined in 430 patients
      with ESCC (241 German Caucasians and 189 northern Chinese) and 397 unrelated
      healthy controls (256 German Caucasians and 141 northern Chinese). RESULTS: A
      significant difference in MTHFR C677T genotype distribution was observed between
      German Caucasian controls (C/C, 41.8%, C/T, 44.9%, T/T, 13.3%) and northern
      Chinese controls (C/C, 17.7%, C/T, 38.3%, T/T, 44.0%) (chi(2)=52.19, P<0.001).
      The distribution of the MTHFR C677T genotypes among German ESCC patients (C/C,
      39.0%, C/T, 48.1%, T/T, 12.9%) was not significantly different from that among
      healthy controls (chi(2)=0.531, P=0.767). In contrast, the frequency of the C/C
      genotype among Chinese ESCC patients (8.5%) was significantly lower than among
      Chinese healthy controls (17.7%) (chi(2)=6.37, P=0.012). The C/C genotype was
      correlated with a significantly reduced risk for the development of ESCC as
      compared to the combination of C/T and T/T genotypes (adjusted OR=0.38, 95%
      CI=0.16-0.88). CONCLUSIONS: Our results suggest that, in contrast to German
      Caucasians, the MTHFR 677CC homozygous wild-type plays a protective role in the
      development of ESCC in the northern Chinese population.

PMID- 15449188
TI  - Tumour lysis syndrome in multiple myeloma after bortezomib (VELCADE)
      administration.
AB  - Bortezomib (VELCADE) is a proteasome inhibitor, which has been recently used for
      the treatment of relapsed/refractory multiple myeloma (MM) with encouraging
      results. Tumour lysis syndrome (TLS) has been described during chemotherapy for
      many haematological malignancies, such as acute lymphoblastic leukaemia and high
      grade lymphomas. TLS is very rare in MM with ten reported cases, including
      approximately 1% of patients receiving high-dose chemotherapy with stem cell
      support (ASCT). We report here a patient with refractory MM and deletion 13q, who
      had received more than four lines of previous treatment, including two ASCT, and
      had relapsed. The patient received bortezomib, as a single agent, at a dose of
      1.3 mg/m(2) twice per week for 2 weeks, in a 3-week cycle, and developed TLS
      after the second dose of cycle one. Bortezomib therapy, due to the rapidity of
      its action, may result in TLS in myeloma patients who have rapidly proliferative
      disease with a high tumour burden. Therefore, TLS should be looked for during the
      first cycle of bortezomib treatment and suitable precautions should be
      considered.

PMID- 15449189
TI  - A variant presentation of transverse testicular ectopia due to abnormal insertion
      of the gubernaculum.

PMID- 15449190
TI  - Mechanisms for solubilization of cobalt, copper and nickel from Indian Ocean
      nodules at near neutral pH by a marine isolate.
AB  - Polymetallic ocean nodules offer an alternative source for extracting valuable
      strategic metals like Cu, Co and Ni. A novel biodissolution process was carried
      out, employing the cell-free spent growth medium from a marine organism (
      Bacillus M1) isolated from nodules; and Cu, Co and Ni solubilization from the
      nodules was observed to be beyond the theoretical solubility limits at near
      neutral pH. Different characterization techniques revealed the presence of
      phenolic substances in the spent growth medium, which might have formed soluble
      complexes with the transition metals. The low prevailing E(h) redox value in the
      medium suggested a strong reducing environment, favoring the reductive
      dissolution of the oxides. A correlation study of dissolution of Cu, Co and Ni
      with that of Mn and Fe in the nodules was made to investigate the mechanisms of
      metal solubilization by the marine isolate. Under the influence of a strong
      reducing environment coupled with complexation by a phenolic substance present in
      the spent growth medium, Mn and Fe oxides were solubilized from the nodules,
      resulting in concomitant dissolution of Cu, Co and Ni associated with them in the
      nodules.

PMID- 15449191
TI  - Large clostridial cytotoxins.
AB  - The large clostridial cytotoxins are a family of structurally and functionally
      related exotoxins from Clostridium difficile (toxins A and B), C. sordellii
      (lethal and hemorrhagic toxin) and C. novyi (alpha-toxin). The exotoxins are
      major pathogenicity factors which in addition to their in vivo effects are
      cytotoxic to cultured cell lines causing reorganization of the cytoskeleton
      accompanied by morphological changes. The exotoxins are single-chain protein
      toxins, which are constructed of three domains: receptor-binding, translocation
      and catalytic domain. These domains reflect the self-mediated cell entry via
      receptor-mediated endocytosis, translocation into the cytoplasm, and execution of
      their cytotoxic activity by an inherent enzyme activity. Enzymatically, the
      toxins catalyze the transfer of a glucosyl moiety from UDP-glucose to the
      intracellular target proteins which are the Rho and Ras GTPases. The covalent
      attachment of the glucose moiety to a conserved threonine within the effector
      region of the GTPases renders the Rho-GTPases functionally inactive. Whereas the
      molecular mode of cytotoxic effects is fully understood, the mechanisms leading
      to inflammatory processes in the context of disease (e.g., antibiotic-associated
      pseudomembranous colitis caused by Clostridium difficile) are less clear.

PMID- 15449192
TI  - Group structure of the membrane shape equation.
AB  - The purpose of this paper is to study the geometry in the plane of the membrane
      equation or a section equation of a general membrane shape, where the invariance
      under the group of contact transformations is required. The discussion is mainly
      based on Cartan's theory of the Lie group. One may find that the relative
      invariance does not vanish, it is also possible to define a generalized geometry
      in the plane with the elements of contact of the second order x, y, y', y'' as
      the elements of the space and with a certain five-parameter group as its
      fundamental group. In the example of axisymmetric membrane shape equation, one
      may find that the membrane shape is a five-parameter group and characterized by
      twelve group structure parameters which are functions of pressure difference,
      tensile stress and asymmetry effect of the membrane or its environment. When
      these varieties of membrane or environment change, the structure constants vary;
      then one can obtain directly the change of symmetric group and the information on
      the membrane shape variation.

PMID- 15449193
TI  - Phase behaviour of n-hexane/perfluoro-n-hexane binary thin wetting films.
AB  - We present X-ray reflectivity investigations of the concentration distribution in
      binary liquid thin films on silicon substrates. The liquid-vapor coexistence of
      the binary mixture investigated, hexane and perfluorohexane, is far from
      criticality. Therefore, a sharp interface separates the liquid film from the
      vapor. The data reveal a separation of the film in layers parallel to the
      substrate. A phase diagram is constructed as a projection to the (composition
      difference, temperature) space, covering a temperature range corresponding to the
      one-phase and the two-phase regime of the bulk liquid. Although the composition
      data indicate a mixing gap similar to that of the bulk system, there are two
      major differences: i) only the near-surface phase changes its composition
      significantly, and ii) a composition gradient in the film exists also at higher
      temperatures where in the bulk system the one-phase regime exists.

PMID- 15449194
TI  - On the conformation and the structure of polymacromonomers.
AB  - Using poly(omega-norbornenyl polystyrene) as a model we studied the conformation
      and the structure of branched polymer chains each of whose backbone constitutive
      units bear a branch. The parameters taken into account are: the polymerisation
      degree of the backbone, the molar mass of the branches and the solution
      concentration. The effect of the global conformation of these polymacromonomers,
      either spherically or cylindrically (vermiform) symmetric, is considered. The
      compactness of the polymer constitutive unit distribution, the branches and the
      backbone conformations are considered as functions of the first two parameters
      above. Significant results are obtained on all of these three points.

PMID- 15449195
TI  - Quantitative description of foam drainage: transitions with surface mobility.
AB  - We have performed forced drainage experiments on aqueous foams of bubble
      diameters D varying from 0.18 to 8 mm, and made with different surfactant and
      protein solutions (providing different surface viscoelastic properties). Changing
      bubble size or surface properties allows to evolve between two drainage regimes,
      the respective dimensionless permeabilities also varying with these parameters.
      We show that the bubble size and surface properties can be incorporated into a
      single surface mobility parameter that controls the transition between the two
      drainage regimes. The permeability measurements indicate how do the hydrodynamic
      resistances of the foam channels and nodes depend on surface mobility. Taking
      advantage of the large range of experimental conditions, leading to a variation
      of the mobility parameter over more than 3 decades, a simple and consistent
      description of both the drainage regimes and the transition in between them is
      obtained. For the smallest bubbles (D < 0.5 mm) anomalous behaviors are observed
      and discussed.

PMID- 15449196
TI  - Onset of shear thickening in a simple fluid.
AB  - We report on nonequilibrium molecular-dynamics simulations of the shear
      thickening transition in a simple fluid under shear. We relate the shear
      thickening transition to the onset of instabilities in the flow profile and to
      that of dramatic variations in normal stress differences. The dependence of the
      critical shear rate, which indicates the onset of shear thickening, on density
      and temperature is rationalized by introducing a ratio between two characteristic
      times, quantifying the short-time mobility of a particle and the deformation
      imposed by the applied shear rate, respectively. The shear-thickening transition
      is shown to occur at a constant value for this ratio for all state points
      studied. From a structural point of view, this transition is accompanied by the
      formation of clusters as recently observed in experiments on complex fluids.

PMID- 15449197
TI  - Cervical spondylotic myelopathy and radiculopathy treated by oblique corpectomies
      without fusion.
AB  - Oblique corpectomy (OC) is an alternative technique for the resection of
      spondylotic spurs ventral to the cervical spinal cord contributing to cervical
      spondylotic myelopathy (CSM) and cervical spondylotic radiculopathy (CSR). To
      evaluate the efficacy of OC for the treatment of cervical spondylotic
      myeloradiculopathy, we reviewed our experience with OC. Twenty-six patients, 18
      males and 8 females, were studied. They averaged 51.3 years of age (range 30-72),
      Thirteen had myelopathy and 13, radiculopathy. Both magnetic resonance (MR)
      imaging and computed tomography (CT) were performed preoperatively to define the
      extent of pathology. The Modified Japanese Orthopedic Association (JOA) score was
      used to grade the quality of the outcome. Neurologic and radiologic results were
      assessed. Good and excellent results were observed in 76.9% of the cases with
      myelopathy. Improvement of radicular symptoms was noted in 84.6% of the cases
      with radiculopathy. Neuroimaging studies confirmed satisfactory anatomical
      decompression in all patients. Sagittal alignment decreased from 13 degrees to 12
      degrees. The degree of postoperative recovery seemed to be directly related to
      the age and severity of the preoperative myelopathy. This surgical technique has
      shown excellent clinical outcomes with fast recovery and adequate anatomical
      decompression in patients with CSM and CSR.

PMID- 15449198
TI  - Non-enhancing de novo glioblastoma: report of two cases.
AB  - Malignant gliomas arise from two distinct pathways, as de novo lesions or from
      secondary transformation from low-grade lesions. Herein, we describe the cases of
      two patients to illustrate the proposition that de novo malignant gliomas can
      originate as non-enhancing tumors and rapidly progress to a pattern of ring
      enhancement characteristic of a glioblastoma. Both patients presented with new
      onset seizures (simple partial and generalized). Their neurological examinations
      were unremarkable. Initial MRI evaluations revealed a right precentral gyrus and
      right medial temporal lobe lesions in each case, respectively. These lesions
      demonstrated increased T2 signal changes without contrast enhancement. The biopsy
      of the right frontal lesion in the first patient was consistent with an
      anaplastic astrocytoma; the second patient was followed expectantly. Repeat MRI
      for both patients within 17 weeks disclosed ring-enhancing lesions, consistent
      with an unusually rapid evolution to glioblastoma multiforme (GBM). Subsequent
      resection of the right medial temporal lesion in the second patient revealed a
      GBM. Neither tumor displayed abnormal overexpression of P53 by
      immunohistochemistry. Early MRI of de novo glioblastomas may demonstrate a non
      enhancing tumor suggestive of a low-grade lesion. These tumors can rapidly evolve
      into ring-enhancing lesions more consistent with the traditional imaging
      findings.

PMID- 15449199
TI  - Sentinel node mapping for gastric cancer: is the jury still out?

PMID- 15449200
TI  - Submitting an article on gastric cancer: to which journal?

PMID- 15449201
TI  - TNM and Japanese staging systems for gastric cancer: how do they coexist?
AB  - Two staging systems for gastric cancer, International Union Against Cancer
      (UICC)/TNM and the Japanese classification, have been used widely for clinical
      practice and research. The two systems started independently in the 1960s, and
      underwent several revisions and amendments in order to approach each other, but
      have become more divergent in the latest editions because of characteristics
      based on different philosophies. The TNM system adopted a number-based system for
      N-staging that provides easy and accurate prognostic stratification. Comparative
      studies have shown that the TNM system has greater prognostic power than the
      Japanese classification. It contains, however, no treatment guidance and should
      primarily be used as a guide to prognosis. In contrast, the Japanese
      classification has been designed as a comprehensive guide to treatment,
      originally for surgeons and pathologists, and today for oncologists and
      endoscopists as well. Its anatomical-based N-staging was established based on
      analysis of lymphadenectomy effectiveness, and naturally provides direct surgical
      guidance. Clinicians should understand the roles of each system and must not mix
      the systems or terminology when they report their study results.

PMID- 15449202
TI  - An assessment of the feasibility of sentinel lymph node-guided surgery for
      gastric cancer.
AB  - BACKGROUND: Sentinel node-guided surgery has received increasing attention in
      tumor surgery. To ascertain whether sentinel lymph node (SLN)-guided surgery is
      feasible for gastric cancers 4 cm or less in size, we conducted a multicenter
      clinical study. METHODS: One milliliter of isosulfan blue was injected
      endoscopically into the gastric wall at four sites around a gastric cancer
      lesion. Approximately 15 min after the injection of the dye, the surgeons
      resected (picked-up) the stained blue nodes (defined as SLNs) around the stomach.
      RESULTS: SLNs were detected in 140 of 144 patients (97.2%). The average number of
      SLNs was 3.3. In 99 patients with D2 lymph node dissection, the false-negative
      rate (FNR) was evaluated. In 14 T1 patients with pathological positive lymph node
      metastasis (pN(+)), the FNR was 29%. In 9 T2,3 pN(+) patients, the FNR was 44%.
      In T1 patients with pN(+) but macroscopically normal lymph nodes during surgery
      (sN0), the FNR was 11% (1/9). CONCLUSION: T1 and sN0 patients may be a target
      group for the study of SLN-guided surgery. A larger multicenter trial should be
      performed to clarify the application of sentinel node navigation surgery for
      gastric cancer.

PMID- 15449203
TI  - Pathologic characteristics of gastric cancer in the elderly: a retrospective
      study of 994 surgical patients.
AB  - BACKGROUND: The clinicopathologic features of gastric carcinoma in elderly people
      have been reported previously. The present study examined the patterns and
      distribution of gastric carcinomas in the elderly, especially in patients aged 85
      and older. METHODS: A retrospective study of 994 consecutive Japanese patients
      aged 65 years or older was performed. In this group, a total of 1,147 lesions
      were analyzed. Pathological findings in the very old group (older than 85 years;
      n = 126) were compared with those in younger groups (65-74 years [young-old
      group]; n = 356) and (75-84 years [middle-old group]; n = 512). RESULTS: While
      the male-to-female ratio significantly decreased with advancing age, the relative
      odds of gastric cancer in men were higher than those in women in all age groups.
      In the very old group, cancer of the lower third of the stomach tended to
      increase with advancing age, and accounted for 43.7% of cases. In the population
      overall, differentiated-type adenocarcinoma accounted for 89.6% in the early
      cancers and 50.3% in the advanced cancers. The proportion of cases involving
      differentiated-type carcinoma significantly increased with advancing age in early
      cancer and female advanced cancer cases, whereas no significant change was found
      in male advanced-cancer patients. In the very old group, lymph node metastasis
      was found in 5.4% of early cancers and 72.7% in advanced cancers. Multiple
      cancers significantly increased with advancing age ( P < 0.05; 10.7% in the
      younger-old group, 12.7% in the middle-old group, and 19.0% in the very old
      group). CONCLUSION: These results indicate that, in the very old group, gastric
      cancers showed a distal shift with predominantly differentiated-type carcinoma in
      the early stages and increased undifferentiated-type carcinomas in advanced
      stages. These results suggest increased histologic diversity with tumor growth.
      These findings have important implications for the screening and diagnosis of
      gastric cancer in the elderly.

PMID- 15449204
TI  - Regulation of drug sensitivity of gastric cancer cells by human calcyclin-binding
      protein (CacyBP).
AB  - BACKGROUND: Calcyclin-binding protein (CacyBP) was previously identified as an
      upregulated gene in a multidrug-resistant gastric cancer cell line, SGC7901/ADR,
      compared to its parental cells, SGC7901, by subtractive hybridization. The aim of
      this study was to explore the role of CacyBP in multidrug resistance (MDR) in
      gastric cancer cells. METHODS: The cDNA encoding CacyBP was generated by reverse
      transcription-polymerase chain reaction (RT-PCR), and mouse antisera against
      CacyBP was raised using recombinant CacyBP as the immunogen. The expression of
      CacyBP in gastric cancer cells was determined by Northern and Western blots.
      Sense and antisense vectors for CacyBP were introduced into SGC7901 and
      SGC7901/ADR cells, respectively. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl
      tetrazolium bromide (MTT) assay was performed to evaluate the drug sensitivity of
      gastric cancer cells. Flow cytometry was employed to determine adriamycin
      accumulation and retention in gastric cancer cells. RESULTS: Northern and Western
      blots demonstrated upregulation of CacyBP in SGC7901/ADR cells compared to
      SGC7901 cells. SGC7901-CacyBP and SGC7901/ADR-anCacyBP cells were prepared, in
      which CacyBP was genetically increased and decreased, respectively. As compared
      with SGC7901, SGC7901-CacyBP cells exhibited significantly increased ( P < 0.01)
      IC(50) values for vincristine, adriamycin, and 5-fluorouracil. Meanwhile, as
      compared with SGC7901/ADR, SGC7901/ADR-anCacyBP cells exhibited significantly
      decreased ( P < 0.01) IC(50) values for these three drugs. SGC7901-CacyBP and
      SGC7901/ADR-anCacyBP cells displayed no obvious difference ( P > 0.05) in
      intracellular adriamycin content compared to their corresponding parental cells.
      CONCLUSIONS: Upregulation of CacyBP is associated with MDR in gastric cancer
      cells. CacyBP could regulate the responses of gastric cancer cells to
      chemotherapy. But the underlying mechanisms of CacyBP-related MDR need further
      identification.

PMID- 15449205
TI  - Prospective randomized study of two laparotomy incisions for gastrectomy: midline
      incision versus transverse incision.
AB  - BACKGROUND: We performed a randomized study to evaluate the differences between
      upper midline incision and transverse incision for gastrectomy. METHODS: Patients
      undergoing distal gastrectomy or total gastrectomy for gastric cancer were
      randomly allocated to have either an upper midline incision or a transverse
      incision. The times taken to open and close the abdominal cavity, the number of
      doses of postoperative analgesics, and the incidence of postoperative pneumonia,
      wound infection, and intestinal obstruction were compared between the patients
      having the two incisions. RESULTS: Times for both opening and closing the
      abdominal cavity were longer with a transverse incision, in both the distal
      gastrectomy group and total gastrectomy group. In the patients in whom continuous
      epidural analgesia was used postoperatively, the number of additional doses of
      analgesics was smaller in the transverse-incision group after distal gastrectomy.
      The incidence of postoperative pneumonia was lower in the transverse-incision
      group after distal gastrectomy. The number of patients with postoperative
      intestinal obstruction was smaller in the transverse-incision group than in the
      midline-incision group after distal gastrectomy. In contrast to distal
      gastrectomy, there was no significant difference in the number of doses of
      postoperative analgesics, incidence of postoperative pneumonia, or incidence of
      postoperative intestinal obstruction between the two study groups after total
      gastrectomy. CONCLUSION: A transverse incision for distal gastrectomy may be more
      beneficial than an upper midline incision in attenuating postoperative wound
      pain, decreasing the incidence of postoperative pneumonia, and preventing
      postoperative intestinal obstruction.

PMID- 15449206
TI  - An appraisal of gastric cancer research in cancer journals.
AB  - We assessed the trends in the proportion of articles on gastric cancer published
      in major cancer journals, the research fields of interest, and the first author's
      affiliation. Articles in PubMed, addressing cancer in general and stomach cancer
      in particular, were quantified. Abstracts of gastric cancer articles were hand
      searched. The British Journal of Cancer, Cancer, Cancer Research, the
      International Journal of Cancer, and the Journal of the National Cancer Institute
      were included in the journal survey. Stomach cancer was addressed in 2.9% of the
      articles in 1982-1984 and 3.3% in 2000-2002. The proportion of articles from Asia
      increased (32.2% vs 50.2%) and that for the United States decreased (34.4% vs
      15.1%) in 2000-2002. Articles addressing etiologic genetic factors were more
      frequent in 2000-2002 (11.5% vs 61.6%). The proportion of stomach cancer articles
      was largely below the expected share considering the frequency of malignancies,
      and did not reflect the geography of biomedical publications. A trend was
      observed favoring the evaluation of genetic factors.

PMID- 15449207
TI  - Route from the paraaortic lymphatic system to the tracheobronchial lymph nodes
      evidenced on lymphangiogram in a patient with gastric cancer.
AB  - Lung metastasis from gastric or colonic cancer, without liver metastasis, is
      seldom seen. However, its metastatic pathway has not been delineated on imaging.
      We present and discuss such a lymphatic route in a patient with gastric cancer.
      The appearance of the mediastinum on a lymphangiogram is discussed. To the best
      of our knowledge, the lymphangiographic demonstration of the route from the
      paraaortic lymphatics to the tracheobronchial lymph nodes has been not reported.
      Lymphatics running from the paraaortic to the tracheobronchial lymph nodes
      through the diaphragm may play an important part in direct metastasizing to lung
      or tracheobronchial lymph nodes in certain patients.

PMID- 15449208
TI  - Gastric carcinoma in a 13-year-old girl.
AB  - Gastric cancer is uncommon before the fifth decade of life. The appearance of
      adenocarcinoma in young adults has motivated molecular studies that aimed to
      identify inherited mutations. Moreover, carcinoma of the stomach in the young
      adult is sufficiently rare to generate considerable interest in each occurrence
      of it, especially when it occurs in the gastroesophageal junction. We report a
      case of gastric carcinoma in a 13-year-old girl, who was referred to our service
      with weakness, malaise, weight loss, and slight dysphagia. An upper endoscopy
      with biopsy revealed a gastric Borrmann III tumor, with invasion of the distal
      esophagus; histopathological analysis revealed a moderately differentiated
      adenocarcinoma. During staging, she was diagnosed with several metastases,
      including the lymph nodes, liver, spleen, and ovary. She was referred for
      radiochemotherapy and died within 4 months. We should consider and investigate
      the possibility of malignancy even in young patients with persistent symptoms or
      anemia, in order to diagnose this malignancy at earlier stages.

PMID- 15449209
TI  - Comment on "Subtotal versus total gastrectomy for T3 adenocarcinoma of the
      antrum".

PMID- 15449210
TI  - Tissue ablation-rate measurements with a long-pulsed, fibre-deliverable 308 nm
      excimer laser.
AB  - This ablation rate study has been carried out with a fibre-deliverable, 308 nm,
      XeCl laser, producing long pulses of 200 ns as opposed to the usual 10-20 ns.
      This in-depth study aimed to evaluate the ablation rates for this longer pulse
      length. The effects on the ablation depth of dentine, enamel, soft tissue and
      bone were investigated ex vivo. Radiant exposure, number of pulses, pulse
      repetition rate and spot size were independently varied. For all tissues,
      ablation depth per pulse was found to increase, initially, linearly with radiant
      exposure. For both dentine and soft tissue a saturation radiant exposure was
      determined; thereafter the ablation rate decreased. The depth per pulse increased
      linearly with repetition rate but decreased logarithmically with both number of
      pulses and spot size. The ablation depth due to a 200 ns pulse is comparable to
      that caused by a 10-20 ns pulse but has the advantage of fibre delivery.

PMID- 15449215
TI  - Neurophysiological mechanisms of sleep and wakefulness: a question of balance.
AB  - Following a summary of the stages of sleep and wakefulness as monitored with the
      electroencephalogram and electromyogram, important aspects of the neurophysiology
      and neuroanatomy of the circuits of vigilance state control are reviewed. A
      homeostatic drive for sleep and a circadian influence work in concert to
      determine sleepiness. These processes influence sleep-promoting and central
      arousing neuronal systems, the former dependent on a group of neurons in the
      hypothalamic ventrolateral preoptic area and the latter governed by neurons in
      the pons and basal forebrain. The interactive neuronal circuit that is formed by
      these cell groups ensures the balance between sleep and wakefulness and the rapid
      transition to and from sleep. As sleep deepens, the switch to rapid eye movement
      (REM) sleep occurs. This transition can also be viewed as a balance between one
      group of pontine neurons that discharge only during REM sleep and another group
      that cease to discharge during REM sleep. This article concludes with future
      perspectives based on the recent discovery of the orexin cell group. Orexinergic
      neurons may be critical both for promoting wakefulness at certain times in the
      daily cycle and for controlling the switch into REM sleep.

PMID- 15449216
TI  - Approach to the patient with a sleep complaint.
AB  - There have always been sleep disorders, many of which have been recognized for
      centuries, and some of our treatments have even been dated from the past.
      However, there has been a dramatic increase in knowledge about sleep disorders
      and their treatments in the past 20 years. It is now possible to objectively
      diagnose most sleep disorders and new, specific treatments can be instituted. The
      recent recognition of chronobiology has resulted in an understanding of the
      alterations in the sleep-wake pattern of humans. Genetic causes of sleep
      disorders, such as advanced sleep phase syndrome, have shed new light on
      disorders that were previously believed to be largely behaviorally produced.
      Neurochemical changes have led to a better understanding of the pathophysiology
      of some disorders such as narcolepsy. However, despite advances in our
      understanding of sleep disorders, accurate diagnosis and treatment always
      requires a detailed understanding of the patient's sleep-wake cycle and medical
      history. The art of good sleep medicine still lies in the ability of the
      clinician to take a thorough history, develop a differential diagnosis, and
      formulate a treatment plan. This article details the important elements of the
      clinical evaluation.

PMID- 15449217
TI  - The use of sleep studies in neurological practice.
AB  - In recent years, sleep medicine has become a rapidly advancing field filled with
      exciting new discoveries. Many sleep disorders are diagnosed by clinical history
      alone. Sleep disorders such as sleep apnea, narcolepsy, periodic limb movement
      disorder, parasomnias, and nocturnal seizures usually require evaluation in the
      sleep laboratory. Sleep studies are used for diagnostic purposes, to assess
      disease severity, and to evaluate treatment efficacy. Sleep testing should be
      tailored to answer the specific clinical question at hand. This article reviews
      the techniques most commonly performed in the sleep laboratory and their
      indications, interpretation, and limitations. These include the polysomnogram,
      the multiple sleep latency test, and the maintenance of wakefulness test. The
      accurate interpretation of these studies requires a comprehensive sleep and
      medical history.

PMID- 15449218
TI  - The restless legs syndrome and periodic limb movement disorder: a review of
      management.
AB  - The restless legs syndrome (RLS) and periodic limb movement disorder (PLMD) are
      distinguishable but overlapping disorders. Both feature nocturnal involuntary
      limb movements (periodic limb movements) that can cause sleep disruption, but
      each has distinct clinical features that are relevant to the diagnosis and
      management of the patient. The diagnosis of RLS is made by meeting established
      clinical criteria, not from discovery of periodic limb movements of sleep (PLMS)
      on a sleep study. PLMD, however, does require the presence of PLMS on
      polysomnography as well as an associated sleep complaint. Moreover, PLMS are
      themselves nonspecific, occurring both with RLS and with other sleep disorders as
      well as in normal individuals. The diagnosis of PLMD, then, requires not merely
      finding a significant number of PLMS but also excluding other potential causes
      for the associated sleep complaint. Treatment of RLS is based on consideration of
      the pattern and severity of the disorder, with dopaminergic drugs generally
      favored for initial treatment. Anticonvulsants, opioids, and sedative/hypnotics
      also have a role. A treatment algorithm is provided to assist with the management
      of RLS. Treatment of PLMD relies on many of the same medications, but is
      generally more straightforward and places a greater reliance on levodopa
      compounds and sedative-hypnotics.

PMID- 15449219
TI  - Neurological perspective on obstructive and nonobstructive sleep apnea.
AB  - One of every 15 adults in the United States has at least moderate sleep apnea.
      The true prevalence is higher, as approximately 0.3 to 5% of adults with sleep
      apnea are undiagnosed. Sleep apnea has major health consequences; therefore,
      neurologists must recognize and treat sleep apnea syndromes appropriately. There
      are three main categories of sleep apnea: obstructive sleep apnea (OSA), central
      sleep apnea (CSA), and mixed sleep apnea. OSA results from upper airway
      obstruction, and CSA is due to lack of inspiratory muscle effort; mixed apnea
      results from a combination of these factors. Sleep apnea syndromes can present
      within the spectrum of "typical" neurological complaints, including
      forgetfulness, headaches, sleepiness, fatigability, seizures, and muscle and
      nerve weakness. A good sleep history, a nocturnal polysomnogram, and multiple
      sleep latency test are important in elucidating the diagnosis and validating the
      complaints of sleepiness. The gold standard for treatment of OSA is positive
      airway pressure, although some patients may benefit from surgical interventions
      designed to bypass the site of airway obstruction. With CSA, treatment is
      directed toward the underlying disorder. Patients with CSA may also benefit from
      several types of nasal positive airway pressure treatment, while some require
      mechanical ventilation.

PMID- 15449220
TI  - Narcolepsy and syndromes of primary excessive daytime somnolence.
AB  - Excessive daytime sleepiness (EDS) or somnolence is common in our patients and in
      society in general. The most common cause of EDS is "voluntary" sleep
      restriction. Other common causes include sleep-fragmenting disorders such as the
      obstructive sleep apnea syndrome. Somewhat less familiar to the clinician are EDS
      conditions arising from central nervous system dysfunction. Of these so-called
      primary disorders of somnolence, narcolepsy is the most well known and
      extensively studied, yet often misunderstood and misdiagnosed. Idiopathic
      hypersomnia, the recurrent hypersomnias, and EDS associated with nervous system
      disorders also must be well-understood to provide appropriate evaluation and
      management of the patient with EDS. This review summarizes the distinguishing
      features of these clinical syndromes of primary EDS. A brief overview of the
      pharmacological management of primary EDS is included. Finally, in view of the
      tremendous advances that have occurred in the past few years in our understanding
      of the pathophysiology of canine and human narcolepsy, we also highlight these
      discoveries.

PMID- 15449221
TI  - Parasomnias.
AB  - Parasomnias are defined as unpleasant or undesirable behavioral or experiential
      phenomena that occur predominately or exclusively during the sleep period.
      Initially thought to represent a unitary phenomenon, often attributed to
      psychiatric disease, it is now clear that parasomnias are not a unitary
      phenomenon but rather are the manifestation of a wide variety of completely
      different conditions, most of which are diagnosable and treatable. The
      parasomnias may be conveniently categorized as "primary sleep parasomnias"
      (disorders of the sleep states per se) and "secondary sleep parasomnias"
      (disorders of other organ systems, which manifest themselves during sleep). The
      primary sleep parasomnias can be classified according to the sleep state of
      origin: rapid eye movement (REM) sleep, non-REM (NREM) sleep, or miscellaneous
      (i.e., those not respecting sleep state). The secondary sleep parasomnias can be
      further classified by the organ system involved. The underlying pathophysiology
      of many parasomnias is state dissociation-the brain is partially awake and
      partially asleep. The result of this mixed state of being is that the brain is
      awake enough to perform very complex and often protracted motor and/or verbal
      behaviors but asleep enough not to have conscious awareness of, or responsibility
      for, these behaviors.

PMID- 15449222
TI  - Nocturnal seizures.
AB  - As a subset of epilepsy, nocturnal seizures amplify one of the major problems of
      epilepsy in general: episodes are less likely to be directly witnessed than
      daytime seizures, and therefore diagnosis and characterization are more
      difficult. As a sleep problem, nocturnal seizures are not benign, and the
      resulting sleep disruption can cause daytime somnolence and concentration
      difficulty. This article outlines three major topics in nocturnal seizures:
      differential diagnosis (distinguishing between seizures and parasomnias), the
      effects of nocturnal seizures on sleep structure, and specific syndromes of
      primarily or exclusively nocturnal seizures.

PMID- 15449223
TI  - Sleep and epilepsy.
AB  - The relationship of sleep and epilepsy demonstrates the delicate association of
      brain physiology and dysfunction. Sleep affects the distribution and frequency of
      epileptiform discharges in humans and influences the rate of kindling in animals.
      Epileptic discharges, on the other hand, alter sleep regulation and provoke sleep
      disruption. This effect on sleep appears to carry over to sleep complaints in
      patients with epilepsy. Individuals with epilepsy frequently complain of symptoms
      suggestive of disturbed sleep, such as excessive daytime sleepiness, insomnia, or
      with more subtle complaints such as an increase in seizure frequency. More
      commonly, these symptoms indicate an underlying sleep disorder rather than the
      effect of epilepsy or medication on sleep. Clinicians must be able to identify
      and differentiate between potential sleep disorders and sleep dysfunction related
      to epilepsy and direct therapy to improve the patient's symptoms. The reciprocal
      relationship of sleep and epilepsy and the management of sleep complaints in the
      patient with epilepsy will be reviewed.

PMID- 15449224
TI  - Circadian rhythm disorders.
AB  - Circadian rhythm sleep disorders occur when individuals attempt to sleep at the
      wrong circadian time. The misalignment between the internal circadian timing
      system and the external environment is typically due to either an alteration in
      the functioning of the circadian timing system (e.g., delayed or advanced sleep
      phase syndrome) or to changes in the external environment (e.g., jet lag).
      However, the clinical presentation of most of the circadian rhythm sleep
      disorders is influenced by a combination of physiological, behavioral, and
      environmental factors. These disorders lead to complaints of insomnia and
      excessive daytime sleepiness, with impairment in important areas of functioning
      and quality of life. Current treatments primarily involve the use of circadian
      synchronizing agents, such as light, to realign the internal and external
      environment. These treatments are limited by the availability of adequate
      diagnostic tools and well-controlled clinical trials. A better understanding of
      the pathophysiology of these disorders is required to develop more effective
      treatments.

PMID- 15449225
TI  - Sleep and its disorders in children.
AB  - Although the physiological mechanisms that underlie sleep disorders in children
      differ little from those seen in adults, the clinical manifestations may differ
      considerably between the two. For example, sleep apnea in adults affects men more
      than women, is more prevalent in the obese, and presents with symptoms of snoring
      and excessive somnolence. In preadolescent children, sleep apnea affects both
      sexes equally, is more closely correlated with adenotonsillar enlargement than
      obesity, and may be more likely to present with daytime inattention and learning
      problems rather than frank somnolence. Likewise, the insomnia and associated
      bedtime struggles of a 3-year-old bear little resemblance to the insomnia of a
      mature adult apart from the fact that both individuals are unable to easily fall
      asleep. Sleep disorders in children are reviewed with particular focus on age
      related changes in normal sleep and on sleep disorders that primarily or
      exclusively affect children. Pediatric aspects of other sleep disorders will be
      reviewed in more limited detail, with examination of how age, developmental
      level, and comorbid conditions cause clinical presentation and treatment to
      differ from that of adults.

PMID- 15449226
TI  - Discordance between genetic structure and morphological, ecological, and
      physiological adaptation in Lake Magadi tilapia.
AB  - The Magadi tilapia (Alcolapia grahami, formerly Oreochromis alcalicus grahami) is
      a remarkable example of teleost life in an extreme environment. Typical
      conditions include water pH=10, titration alkalinity>300 mM, osmolality=525 mOsm,
      temperatures ranging from 23 degrees to 42 degrees C, and O(2) levels fluctuating
      diurnally between extreme hyperoxia and anoxia. A number of relatively small
      tilapia populations are present in various thermal spring lagoons around the
      margin of the lake separated by kilometers of solid trona crust (floating
      Na(2)CO(3)) underlain by anoxic water. Despite the apparent isolation of
      different populations, annual floods may provide opportunities for exchange of
      fish across the surface of the trona and subsequent gene flow. To assess the
      question of isolation among Lake Magadi populations, we analyzed the variable
      control region of the mitochondrial DNA (mtDNA) from six lagoons. A total of
      seven mtDNA haplotypes, including three common haplotypes, were observed in all
      six populations. Several of the Lake Magadi populations showed haplotype
      frequencies indicative of differentiation, while others showed very little.
      However, differentiation among lagoon populations was discordant with their
      geographical distribution along the shoreline. All populations exhibited the
      unusual trait of 100% ureotelism but specialized morphological and physiological
      characteristics were observed among several of the lagoon systems. In addition,
      distinct differences were observed in the osmolality among the lagoons with
      levels as high as 1,400-1,700 mOsm kg(-1), with corresponding differences in the
      natural levels of whole-body urea. These levels of osmotic pressure proved fatal
      to fish from less alkaline systems but remarkably were also fatal to the fish
      that inhabited lagoons with this water chemistry. Upon more detailed inspection,
      specific adaptations to differential conditions in the lagoon habitat were
      identified that allowed survival of these cichlids. Additional evidence against
      potential for gene flow among lagoons despite the sharing of common mtDNA
      haplotypes was that the osmolality of floodwaters following a heavy rain showed
      lethal levels exceeding 1,700 mOsm kg(-1). In isolation, different mtDNA
      haplotypes would be predicted to go to fixation in different populations due to
      rapid generation times and the small effective population sizes in a number of
      lagoons. We propose a model of balancing selection to maintain common mtDNA
      sequences through a common selection pressure among lagoons that is based on
      microhabitats utilized by the tilapia.

PMID- 15449227
TI  - Protein synthesis, RNA concentrations, nitrogen excretion, and metabolism vary
      seasonally in the Antarctic holothurian Heterocucumis steineni (Ludwig 1898).
AB  - Seasonal changes in protein and nitrogen metabolism have not previously been
      reported in any Antarctic suspension-feeding species that ceases feeding for
      extended periods in winter. To provide comparison with data reported on Nacella
      concinna, a species that continues to feed in winter, we have measured feeding
      activity; oxygen consumption; ammonia, urea, and fluorescamine-positive substance
      (FPS) excretion; O : N ratios; body wall protein synthesis; RNA to protein
      ratios; and RNA activity at three times during the year in an Antarctic
      suspension-feeding holothurian. Feeding activity ceased for 4 mo during winter,
      and oxygen consumption rates decreased from 8.79+/-0.43 micro mol h(-1) to 4.48+/
      0.34 micro mol h(-1). Ammonia excretion also decreased during winter from 2,600+/
      177 nmol N h(-1) to 974+/-70 nmol N h(-1), but urea excretion rates increased
      from 178+/-36 nmol N h(-1) to 281+/-110 nmol N h(-1), while FPS excretion rates
      remained unchanged throughout the year with a seasonal mean of 88+/-13 nmol N h(
      1). Oxygen to nitrogen ratios ranged between 6 and 10, suggesting that proteins
      were used as the primary metabolic substrate. Body wall protein synthesis rates
      decreased from 0.35%+/-0.03% d(-1) in summer to 0.23% d(-1) in winter, while RNA
      to protein ratios decreased from 33.10+/-1.0 microg RNA mg(-1) protein in summer
      to 27.88+/-1.3 microg RNA mg(-1) protein in winter, and RNA activity was very
      low, ranging between 0.11+/-0.01 mg protein mg(-1) RNA d(-1) in summer and 0.06+/
      0.01 mg protein mg(-1) RNA d(-1) in winter. Heterocucumis steineni shows a larger
      seasonal decrease in oxygen consumption and ammonia excretion between February
      (summer) and July (winter) than N. concinna, while the proportional decrease in
      protein synthesis rates is similar in both species.

PMID- 15449228
TI  - Magnitude and duration of thermal stress determine kinetics of hsp gene
      regulation in the goby Gillichthys mirabilis.
AB  - The stress-induced transcription of heat shock genes is controlled by heat shock
      transcription factor 1 (HSF1), which becomes activated in response to heat and
      other protein denaturants. In previous research on the eurythermal goby
      Gillichthys mirabilis, thermal activation of HSF1 was shown to vary as a function
      of acclimation temperature, suggesting the mechanistic importance of HSF1
      activation to the plasticity of heat shock protein (Hsp) induction temperature.
      We examined the effect of season on the thermal activation of HSF1 in G.
      mirabilis, as well as the relative kinetics of HSF1 activation and Hsp70 mRNA
      production at ecologically relevant temperatures. There was no predictable
      seasonality in the thermal activation of HSF1, perhaps due to the existence of
      stressors, in addition to heat, acting in the field. Concentrations of Hsp70, a
      negative regulator of HSF1, as well as those of HSF1, varied with collection
      date. The rapidity of HSF1 activation and of Hsp70 mRNA synthesis increased with
      laboratory exposure temperature. Furthermore, Hsp70 mRNA production was more
      sustained at 35 degrees C than at 30 degrees C. Therefore, both the magnitude and
      the duration of a heat shock are important in determining the intensity of heat
      shock gene induction.

PMID- 15449229
TI  - Myosin isoform expression and MAFbx mRNA levels in hibernating golden-mantled
      ground squirrels (Spermophilus lateralis).
AB  - Hibernating mammals present many unexplored opportunities for the study of muscle
      biology. The hindlimb muscles of a small rodent hibernator (Spermophilus
      lateralis) atrophy slightly during months of torpor, representing a reduction in
      the disuse atrophy commonly seen in other mammalian models. How torpor affects
      contractile protein expression is unclear; therefore, we examined the myosin
      heavy-chain (MHC) isoform profile of ground squirrel skeletal muscle before and
      after hibernation. Immunoblotting was performed first to identify the MHC
      isoforms expressed in this species. Relative percentages of MHC isoforms in
      individual muscles were then measured using SDS-PAGE (sodium dodecyl sulfate
      polyacrylamide gel electrophoresis). The soleus and diaphragm did not display
      differences in isoforms following hibernation, but we found minor fast-to-slow
      isoform shifts in MHC protein in the gastrocnemius and plantaris. These subtle
      changes are contrary to those predicted by other models of inactivity but may
      reflect the requirement for shivering thermogenesis during arousals from torpor.
      We also measured mRNA expression of the Muscle Atrophy F-box (MAFbx), a ubiquitin
      ligase important in proteasome-mediated proteolysis. Expression was elevated in
      the hibernating gastrocnemius and the plantaris but was not associated with
      atrophy. Skeletal muscle from hibernators displays unusual plasticity, which may
      be a combined result of the intense activity during arousals and the reduction of
      metabolism during torpor.

PMID- 15449230
TI  - General function and endocrine control of the posterior lymph hearts in Bufo
      marinus and Rana catesbeiana.
AB  - The effects of hypervolemia and graded increases in arginine vasotocin (AVT),
      angiotensin II (ANGII), and atrial natriuretic peptide (ANP) on lymph heart
      pressure (P(lh)) and rate (f(lh)) were examined in Bufo marinus and Rana
      catesbeiana. The P(lh) and f(lh) for normally hydrated B. marinus at rest were
      1.45+/-0.01 kPa and 52.8+/-0.38 beats min(-1). The P(lh) and f(lh) were
      significantly lower in R. catesbeiana, 1.05+/-0.01 kPa and 48.4+/-0.35 beats min(
      1). Hypervolemia, induced by intravenous infusion of isotonic saline, stopped the
      lymph hearts at volumes of 0.48%+/-0.06% and 0.32%+/-0.04% body mass in B.
      marinus and R. catesbeiana, respectively, equivalent to an 8% increase of their
      respective plasma volumes. ANP had no effect on P(lh) or f(lh) at any of the
      dosages tested. ANGII decreased f(lh) in both species, approximating the
      physiological range of concentrations. AVT, at physiological concentrations,
      increased P(lh) 48% in B. marinus and 38% in R. catesbeiana without changing
      f(lh) in either species. At higher than physiological dosages, P(lh) and f(lh) in
      both species declined. The results suggest that AVT, normally released during
      hemorrhage and dehydration, would increase lymph heart output and help compensate
      for the hypovolemia. This is a contrary result to previous work using
      supraphysiologic doses of AVT.

PMID- 15449231
TI  - Behavioral and physiological compensation for chronic hypoxia in the sailfin
      molly (Poecilia latipinna).
AB  - This study demonstrates that short-term behavioral and physiological responses
      may permit the sailfin molly Poecilia latipinna to cope successfully with extreme
      hypoxia and suggests an interaction between behavioral response (aquatic surface
      respiration [ASR]) and physiological compensation. Poecilia latipinna acclimated
      to chronic hypoxia (6 wk at 1.0 mg L(-1) O(2)) exhibited higher hemoglobin and
      red blood cell concentrations and a 17%-19% lower critical oxygen tension than
      fish acclimated to normoxia. Ventilation frequency increased twofold under
      acclimation to hypoxia, a response that did not diminish with time. However, the
      use of ASR was an immediate response to hypoxia that decreased over the
      acclimation period. This suggests that gradual physiological compensation
      decreases the threshold for ASR. There was no consistent effect of hypoxia on
      mortality and no effect of hypoxia treatment on the number of gestating females,
      suggesting that plastic behavioral and physiological responses in P. latipinna
      compensate for hypoxia to a degree that mitigates a decrease in survivorship and
      facilitates continued reproduction in a laboratory setting. However, there may be
      predation costs in the field related to ASR.

PMID- 15449232
TI  - Exhaustive exercise does not affect the preferred temperature for recovery in
      juvenile rainbow trout (Oncorhynchus mykiss).
AB  - We tested the hypothesis that juvenile rainbow trout (Oncorhynchus mykiss) would
      select a temperature colder than their acclimation temperature (16 deg +/-1 deg
      C) to minimize postexhaustive exercise metabolic demands and enhance oxygen
      availability. After an initial 3-h exploratory period in a thermal gradient (6
      degrees -25 degrees C), fish selected a temperature of approximately 14 degrees C
      and had a baseline exploratory swimming activity of approximately 60 cm min(-1).
      Subsequently, experimental (chased) fish were individually removed, exhaustively
      exercised for 1.5 min, and replaced. Both control (unchased) and experimental
      fish were allowed to explore the thermal gradient for another 2 h. Immediately
      after being chased, trout had a metabolic profile that was consistent with being
      exhausted; levels of plasma and muscle lactate were 4.38+/-0.25 mmol L(-1) and
      28.0+/-2.0 mmol kg(-1), respectively, and levels of muscle glycogen, adenosine
      triphosphate, and phosphocreatine were 3.89+/-0.95, 4.23+/-0.62, and 3.07+/-0.73
      mmol kg(-1), respectively. Although exploratory swimming activity of the chased
      fish was significantly lower (by 81%) as compared with control fish during the
      first 5 min postchase, differences in the mean, median, and mode values for
      selected temperatures during the next 2 h were neither large (<1 degrees C) nor
      significant (P>0.05). Contrary to our initial hypothesis, these findings suggest
      that juvenile rainbow trout do not select a colder temperature to decrease
      metabolic rate following exhaustive exercise. Instead, rainbow trout selected a
      temperature marginally cooler than their acclimation temperature (16 degrees C)
      regardless of whether they had been previously exhausted.

PMID- 15449233
TI  - Geographic variation of the physiological response to overwintering in the
      painted turtle (Chrysemys picta).
AB  - We compared the physiological responses of latitudinal pairings of painted
      turtles submerged in normoxic and anoxic water at 3 degrees C: western painted
      turtles (Chrysemys picta bellii) from Wisconsin (WI) versus southern painted
      turtles (Chrysemys picta dorsalis) from Louisiana (LA), Arkansas (AR), and
      Alabama (AL), and eastern painted turtles (Chrysemys picta picta) from
      Connecticut (CT) versus C. p. picta from Georgia (GA). Turtles in normoxic water
      accumulated lactate, with C. p. bellii accumulating less than (20 mmol/L) the
      other groups (44-47 mmol/L), but with relatively minor acid-base and ionic
      disturbances. Chrysemys picta bellii had the lowest rate of lactate accumulation
      over the first 50 d in anoxic water (1.8 mmol/d vs. 2.1 for AR C. p. dorsalis,
      2.4 mmol/d for GA C. p. picta, and 2.5 mmol/d for CT C. p. picta after 50 d and
      2.6 mmol/d for AL C. p. dorsalis after 46 d). Northern turtles in both groups
      survive longer in anoxia than their southern counterparts. The diminished
      viability in C. p. dorsalis versus C. p. bellii can be partially explained by an
      increased rate of lactate accumulation and a decreased buffering capacity, but
      for the CT and GA C. p. picta comparison, only buffering capacity differences are
      seen to influence survivability.

PMID- 15449234
TI  - Interpopulation variation in developmental titers of vitellogenin, but not
      storage proteins, in lubber grasshoppers.
AB  - We examined simultaneous plastic and latitudinal interpopulation variation in the
      time course of hemolymph protein titers during egg production in the lubber
      grasshopper. Our goal was to gain insight into possible evolutionary changes in
      the physiology underlying reproductive plasticity. We used lubbers from three
      locations in the United States (Florida [FL], Louisiana [LA], and Georgia [GA]),
      each offered three daily food rations. Previous genetic analysis indicated that
      grasshoppers from FL (the low-latitude population) and GA (the high-latitude
      population) were phylogenetically closer to each other than to LA grasshoppers
      (the intermediate-latitude population). The ages at maximum titers of
      vitellogenin (Vg(max)) and three storage proteins that were referred to as major
      hemolymph proteins (MHP(max)) were used as indices of the progress of oocyte
      development. Age at Vg(max) was affected significantly both by diet and by
      population. Perhaps most importantly, age at Vg(max) was less for GA grasshoppers
      than for FL and LA grasshoppers; this pattern differs from the phylogenetic
      relationships of the populations. Age at MHP(max) was significantly affected only
      by diet and not by population. Hence, the regulation of these proteins may differ
      across populations. Finally, we found no evidence that plasticity of reproductive
      investment in response to food availability differs across populations (as
      indicated by nonsignificant interactions of population and feeding environment).

PMID- 15449235
TI  - Termite digestibility and water and energy contents determine the water economy
      index of numbats (Myrmecobius fasciatus) and other myrmecophages.
AB  - Digestibility by captive numbats for termites was determined by feeding trials to
      be 81%+/-1.2% for Coptotermes sp. and 64%+/-3.3% for Nasutitermes sp. Water, ash,
      and energy content of both the Coptotermes (0.96+/-0.099 mg(dry mass) individual(
      1), 78.0%+/-0.36% water, 5.8%+/-0.31% ash, 23.1+/-0.19 kJ g-1dry total energy)
      and Nasutitermes (0.91+/-0.046 mg(dry mass) individual(-1), 76.7%+/-3.09% water,
      7.5%+/-1.10% ash, 22.7+/-0.36 kJ g-1dry total energy) were similar to values
      measured previously for other termites and for ants and insects in general.
      Numbats have a slow passage time for termites (20-30 h), presumably to enhance
      the digestion of termites. The water economy index (WEI) was 0.2 for captive
      numbats feeding on Coptotermes and 0.25 for Nasutitermes, whereas the WEI
      measured for wild, free-living numbats was 0.29, which corresponds to a
      digestibility of 58%. The WEI of a myrmecophage diet is determined by the energy
      and water contents and digestibilities of termites and ants, in the absence of
      drinking. The WEI for numbats, and other termitivorous mammals as well as
      reptiles, is higher than would be expected for an animal-based diet because of
      their relatively low digestibility (58%-81%) for termites. A high WEI preadapts
      myrmecophages to survival in arid environments without having to drink.

PMID- 15449236
TI  - Cold-induced fever and peak metabolic rate in the nine-banded armadillo (Dasypus
      novemcinctus).
AB  - In response to cold exposure, some mammals, including the nine-banded armadillo
      (Dasypus novemcinctus), exhibit an increase in core temperature. This response,
      which can be qualified as a cold-induced fever, could increase cold tolerance by
      increasing peak metabolic rates because of the Q(10) effects. This hypothesis,
      however, is not compatible with the observation that peak core temperature can
      occur up to 100 min before peak metabolic rate in nine-banded armadillos during
      acute exposure to cold heliox (79% He; 21% O(2)). This temporal separation
      between the timing of peak metabolic rate and core temperature could be the
      result of regional heterothermy, of the confounding effects of activity, or of
      using heliox as a respiratory gas. We tested these potential sources of error by
      exposing nine-banded armadillos to cold air while simultaneously monitoring
      behavior, metabolic rates (V dot o2 and V dot co2), and four core temperatures.
      Cold air exposure resulted in a smaller but significant temporal separation, with
      peak core temperature occurring on average 10 min before peak metabolic rate.
      Animals exhibited low activity levels, and the four core temperatures changed
      according to the same temporal pattern, thus eliminating the possibility that
      activity or regional heterothermy caused the temporal separation. Using a
      conceptual model, we propose that the temporal separation resulted from a rate of
      cooling that was too fast.

PMID- 15449237
TI  - Role of the low-affinity glucocorticoid receptor in the regulation of behavior
      and energy metabolism in the migratory red knot Calidris canutus islandica.
AB  - Plasma corticosterone increases in association with migratory flight in the red
      knot Calidris canutus islandica, suggesting that corticosterone may promote
      migratory activity and/or energy mobilization in this species. This hypothesis is
      supported by general effects of glucocorticoids, which include stimulation of
      locomotion and the mobilization of energy depots. We experimentally examined the
      role of elevated corticosterone levels in the migratory red knot by comparing
      foraging behavior, flight frequency, and plasma metabolites between vehicle
      injected controls and birds treated with RU486, an antagonist to the genomic low
      affinity glucocorticoid receptor (GR). We predicted that RU486 treatment would
      interfere with energy mobilization. However, we expected no effects on flight
      activity because recent studies suggest that glucocorticoids affect locomotion
      through a nongenomic receptor. Finally, because glucocorticoids exert permissive
      effects on food intake, we postulated that RU486 treatment in the red knot would
      interfere with feeding. Results were consistent with the latter prediction,
      suggesting that the GR participates in the promotion of hyperphagia, the intense
      feeding state that is characteristic of the migratory condition. RU486 treatment
      did not affect flight frequency, suggesting that corticosterone may support
      migratory activity through a receptor other than the GR. Energy metabolism (as
      determined through plasma metabolites) was also unaffected by RU486, possibly
      because energetic demands experienced by captive birds were low.

PMID- 15449238
TI  - Ecological implications of body composition and thermal capabilities in young
      antarctic fur seals (Arctocephalus gazella).
AB  - In comparison with other homeotherms, young recently weaned marine mammals in
      high latitudes face exceptional energetic demands when foraging and
      thermoregulating. Lipids are an important source of energy and a major component
      of insulation that allows them to meet these demands. To examine the role of
      lipid stores in a high-latitude pinniped, we measured the body composition and
      thermoregulatory capabilities of Antarctic fur seal (Arctocephalus gazella) pups
      and yearlings by using flow-through respirometry and hydrogen isotope dilution.
      From these data, we constructed a model to examine the importance of postweaning
      fasting capability in free-ranging young fur seals. Resting metabolic rates were
      different for pups and yearlings measured in 0.6 degrees C water, 10.3 degrees C
      water, and ambient air; however, mass and percent lipid as covariates accounted
      for the different metabolic responses in pups and yearlings for all treatments.
      The estimated lower critical temperature for combined pups and yearlings was 14.4
      degrees C, 10 degrees -15 degrees C above water temperatures normally experienced
      by Antarctic fur seals. Modeling predicted that a weaned fur seal pup would
      survive at sea from 9.8 to 36.2 d before succumbing to starvation. The most
      likely maximum travel distance within this time constraint suggests that food
      resources close to the natal rookery are important to first-year survival for
      this species.

PMID- 15449239
TI  - Demonstration of the deposition and modification of dietary fatty acids in
      pinniped blubber using radiolabelled precursors.
AB  - Radioisotopes are commonly used to study the in vivo metabolism and deposition of
      dietary fatty acids in adipose tissue. The application of this approach to
      pinnipeds is problematic because of their large mass and blubber fat content. We
      have developed a method where labelled lipids can be fed to seals at financially
      feasible levels, with the radioactivity in individual fatty acids isolated from
      blubber detected with standard laboratory equipment. A combination of techniques
      including argentation thin layer chromatography, high performance liquid
      chromatography with ultraviolet detection, and independent liquid scintillation
      counting were employed. Juvenile gray seals (Halichoerus grypus) were fed either
      0.5 mCi (3)H-labelled triolein (18:1n-9, n=2) or palmitic acid (16:0, n=2).
      Blubber samples were taken 12 h later, and the radioactivity in individual fatty
      acids was determined. Radioactivity was detected in only 18:1 from the animals
      fed (3)H-labelled triolein, indicating direct deposition without modification.
      Both animals fed (3)H-labelled palmitic acid showed clear peaks of radioactivity
      in 16:0; however, there was also significant activity (23%-29%) found in the
      desaturation product 16:1. Our results demonstrate that this method is
      sufficiently sensitive to track the deposition of labelled dietary lipids as well
      as modification products of ingested fatty acids and will be important in the
      application of fatty acid signatures to study predator diets.

PMID- 15449240
TI  - Evaluating thermoregulation in reptiles: the fallacy of the inappropriately
      applied method.
AB  - Given the importance of heat in most biological processes, studies on
      thermoregulation have played a major role in understanding the ecology of
      ectothermic vertebrates. It is, however, difficult to assess whether body
      temperature is actually regulated, and several techniques have been developed
      that allow an objective assessment of thermoregulation. Almost all recent studies
      on reptiles follow a single methodology that, when used correctly, facilitates
      comparisons between species, climates, and so on. However, the use of operative
      temperatures in this methodology assumes zero heat capacity of the study animals
      and is, therefore, appropriate for small animals only. Operative temperatures
      represent potentially available body temperatures accurately for small animals
      but can substantially overestimate the ranges of body temperature available to
      larger animals whose slower rates of heating and cooling mean that they cannot
      reach equilibrium if they encounter operative temperatures that change rapidly
      through either space or time. This error may lead to serious misinterpretations
      of field data. We derive correction factors specific for body mass and rate of
      movement that can be used to estimate body temperature null distributions of
      larger reptiles, thereby overcoming this methodological problem.

PMID- 15449241
TI  - Family-based association study of synapsin II and schizophrenia.
AB  - Synapsin II has been proposed as a candidate gene for vulnerability to
      schizophrenia on the basis of its function and its location in a region of the
      genome implicated by linkage studies in families with schizophrenia. We recently
      reported positive association of synapsin II with schizophrenia in a case-control
      study (Chen et al. 2004). However, since case-control analyses can generate false
      positive results in the presence of minor degrees of population stratification,
      we have performed a replication study in 366 additional Han Chinese probands and
      their parents by use of analyses of transmission/disequilibrium for three in/del
      markers and three single-nucleotide polymorphisms. Positive association was
      observed for rs2307981 (P =.02), rs2308169 (P =.005), rs308963 (P =.002),
      rs795009 (P =.02), and rs2307973 (P =.02). For transmission of six-marker
      haplotypes, the global P value was.0000016 (5 degrees of freedom), principally
      because of overtransmission of the most common haplotype, CAA/-/G/T/C/-
      (frequency 53.6%; chi (2) = 20.8; P =.0000051). This confirms our previous study
      and provides further support for the role of synapsin II variants in
      susceptibility to schizophrenia.

PMID- 15449242
TI  - Can randomized trial outcomes for carotid endarterectomy be achieved in community
      wide practice?
AB  - The benefit of carotid endarterectomy (CEA) is dependent upon achieving
      procedural outcomes comparable to those observed in randomized trials. We have
      extensively examined outcomes of the procedure in the community with a complete
      medical record (hospital chart) review of over 20,000 Medicare patients
      undergoing CEA in 10 states. In patients with comparable indications, overall
      risk of stroke or death of 6.9% in our Medicare studies was comparable to the
      6.5% combined event rate in the North American Symptomatic Carotid Endarterectomy
      Trial. In asymptomatic patients, however, the overall Medicare study result of
      3.8% was inferior to the benchmark perioperative combined event rate of 1.5%
      achieved in the Asymptomatic Carotid Atherosclerosis Study. Our data demonstrated
      that the randomized trial benchmarks could be achieved or even exceeded at a
      statewide level. Our studies also documented that evidence-based processes that
      can reduce perioperative stroke and death (eg, perioperative antiplatelet
      therapy, patching) are underutilized in the community. Overall process and
      outcomes assessment show considerable room for improvement. All surgeons
      performing CEA should use a system-based approach to ensure that all evidence
      based processes are employed for patients undergoing CEA and should use
      indication stratification to document their own outcomes for the procedure.

PMID- 15449243
TI  - Improved outcomes of carotid endarterectomy: the critical role of vascular
      surgeons.
AB  - Improved outcomes after carotid endarterectomy (CEA) have been related to
      preoperative, intraoperative, and postoperative patient and procedural variables.
      Outcomes after CEA have also been related to other factors that are not clearly
      related to the patient or the procedure, such as performance of the procedure in
      high volume hospitals, by high volume surgeons, and by surgeons specializing in
      vascular surgery. These overlapping surrogate markers of "quality" have been
      widely quoted and may be used by external parties to limit access to vascular
      care; however, these markers have unclear significance when examined
      systematically. Some of the confounding variables that preclude easy
      interpretation of these markers include interest of the surgeon in the care of
      vascular patients, surgical talent, surgical judgment, recognition of patients at
      higher risk for complications, and routine or selective use of adjunctive
      medications such as beta-blockers, statins, and anti-platelet agents. The
      practices of vascular surgeons with excellent outcomes after CEA need to be
      examined critically for these underlying factors that affect not only procedural
      results but also long-term stroke-free survival.

PMID- 15449244
TI  - Carotid endarterectomy: who is the high-risk patient?
AB  - The role of carotid endarterectomy in the prevention of stroke was validated by
      two randomized clinical trials, the North American Symptomatic Carotid
      Endarterectomy (NASCET) and the Asymptomatic Carotid Atherosclerosis Study
      (ACAS). However, these trials excluded patients at high risk for perioperative
      stroke and other morbidity, raising concerns for the applicability of the trial
      results to the general population. Some have also suggested these "high-risk"
      patients are better suited for carotid artery stenting with the belief that
      stenting has lower morbidity and mortality. In this article, we review many of
      the commonly accepted high-risk factors for carotid endarterectomy (CEA) and
      examine their outcomes. High-risk patients are more common than generally
      believed and their outcomes may be the same with carotid endarterectomy as it is
      with carotid stenting. Truly "high-risk" patients with shortened life expectancy
      are best served with no intervention.

PMID- 15449245
TI  - Carotid endarterectomy in patients with contralateral carotid occlusion.
AB  - Total occlusion of the contralateral internal carotid artery has often been
      considered to be a predictor of adverse neurologic outcomes following carotid
      endarterectomy of an ipsilateral carotid stenosis. Results from both the North
      American Symptomatic Carotid Endarterectomy Trial and the Asymptomatic Carotid
      Atherosclerosis Study have suggested this to be true. However, each of these
      trials had relatively few patients with contralateral occlusion in the surgical
      arms of the studies. In contrast to these studies, there are multiple surgical
      series in the literature demonstrating excellent results of carotid
      endarterectomy in patients with contralateral total occlusion. Recently,
      advocates of carotid angioplasty and stenting have suggested that this technique
      may be preferable in patients with a contralateral occlusion because of the
      perceived poor outcomes with surgery. As carotid angioplasty and stenting becomes
      more popular, it is becoming even more crucial to better define those patients
      who are truly at increased risk following carotid endarterectomy; ultimately,
      this will help clinicians decide which patients may derive the most benefits from
      endovascular therapies. With these issues in mind, the purpose of this review is
      to examine results of carotid endarterectomy in patients with total occlusion of
      the contralateral carotid artery.

PMID- 15449246
TI  - Carotid endarterectomy with routine electroencephalography and selective
      shunting.
AB  - Carotid endarterectomy requires some sort of cerebral protection in some
      patients. Available strategies include routine shunting, pharmacologic cerebral
      protection, or selective shunting. Selective shunting may be based on
      preoperative criteria or, more commonly, some intraoperative determinant of
      adequacy of cerebral perfusion. There are several commonly used methods, but
      electroencephalography is a sensitive marker for adequacy of cerebral perfusion
      and we have found it an excellent tool in our strategy of selective shunting.
      This article reviews the various approaches to cerebral protection during carotid
      endarterectomy with emphasis on our experience with electroencephalography.

PMID- 15449247
TI  - Eversion versus conventional endarterectomy.
AB  - Changes in surgical techniques may affect outcomes of carotid endarterectomy
      (CEA). Numerous studies have attempted to determine whether eversion CEA is safer
      and more effective than conventional CEA. Randomized controlled trials comparing
      eversion to conventional technique for CEA have been identified and
      systematically analyzed by the Cochrane Stroke Review Group database. Outcomes
      included stroke and death, carotid restenosis/occlusion, and local complications.
      There is evidence that eversion CEA is an effective surgical option comparable to
      conventional CEA. In literature no differences were found between eversion CEA
      and conventional CEA with respect to operative morbidity and mortality. Evidence
      based data indicated that eversion CEA had a lower restenosis rate than
      conventional CEA with primary closure techniques, however, no differences in late
      stroke-free survival rate and superior long-term durability when compared to
      patch closure were found. Recent studies, as well as our single center
      experience, indicate that shunt use in eversion CEA is feasible with comparable
      complication rate versus use of shunt in conventional CEA, although it may
      require specific experience with the technique.

PMID- 15449248
TI  - Patch closure improves results with carotid endarterectomy.
AB  - The type of closure after a carotid endarterectomy, primary closure versus patch
      angioplasty, is controversial. Most authorities agree that in a small carotid
      artery (</=4 mm), particularly in the presence of technical difficulties at the
      internal carotid artery end of the arteriotomy, closing with a patch may avoid
      restenosis. Our randomized prospective studies confirm the conclusions of several
      others that patching in general is superior to primary closure in lowering the
      incidence of perioperative stroke, acute postoperative internal carotid artery
      thrombosis, or both. Both vein patch closure and polytetrafluoroethylene patching
      are superior to primary closure in this regard. Patching (polytetrafluoroethylene
      or saphenous vein patching) is also significantly superior in reducing
      significant recurrent carotid artery stenosis over the long-term. We also
      conclude that for those who like to preserve the saphenous vein, the preferential
      use of polytetrafluoroethylene or Dacron Hemashield Finesse patching may be
      appropriate.

PMID- 15449249
TI  - Critical pathways can improve results with carotid endarterectomy.
AB  - Approximately 10 years ago, the Section of Vascular Surgery at Pennsylvania
      Hospital reported results of critical pathways that we developed for all major
      vascular operations, including carotid endarterectomy (CEA). After implementing
      these pathways, we then developed a specific five-step protocol to further
      improve results and decrease costs for elective CEA. With the advent of carotid
      artery balloon angioplasty and stenting (CABAS), CEA has come under increasing
      attack by endovascular interventionalists. We believe our regimen remains the
      gold-standard against which CABAS should be compared. Our five-step CEA protocol
      includes: (1) duplex ultrasonography performed in an accredited vascular
      laboratory as the sole diagnostic carotid preoperative study, (2) admission the
      day of surgery, (3) cervical block anesthesia to eliminate intraoperative
      electroencephalographic monitoring and other costly intraoperative monitoring
      tests, (4) transfer from the recovery room after a short observation period to
      the vascular ward, and (5) discharge the first postoperative morning. Since this
      5-step protocol was implemented several years ago, we have found it to be safe
      and cost-effective, and now represents the standard against which CABAS should be
      compared.

PMID- 15449250
TI  - Analysis of factors contributing to improved outcome for carotid endarterectomy.
AB  - Since carotid endarterectomy was revitalized following the North American
      Symptomatic Carotid Endarterectomy Trial and Asymptomatic Carotid Atherosclerosis
      Study, results have improved. However, types of carotid endarterectomy,
      indications, risk factors, surgical factors, techniques, and other treatment
      modalities may be associated with outcomes of carotid endarterectomy. The purpose
      of this study was to identify those factors in a broad-based carotid
      endarterectomy patient. This study involved review of the data from 3,644
      patients undergoing carotid endarterectomy in New York State hospitals. A
      multivariate statistical model was used to identify significant patient risk
      factors to examine the association of the process of care and surgical factors,
      including surgical specialty for outcome of carotid endarterectomy. In-hospital
      death and stroke rate overall was 1.84%. After adjustment for patient risk
      factors, specific processes of care, such as eversion endarterectomy, protamine,
      heparin, or shunt, were associated with lower adverse outcomes relative to
      patients undergoing carotid endarterectomy without these processes. Similarly,
      patients undergoing carotid endarterectomy by vascular surgeons had lower adverse
      outcomes compared to neurosurgeons and general surgeons. This retrospective
      review showed that processes of care and surgical specialty were significant
      factors that contributed to outcomes following carotid endarterectomy.

PMID- 15449251
TI  - Chromosome 19p13 loci in Finnish migraine with aura families.
AB  - Chromosomal area 19p13 contains two migraine associated genes: a Ca(v)2.1 (P/Q
      type) calcium channel alpha(1) subunit gene, CACNA1A, and an insulin receptor
      gene, INSR. Missense mutations in CACNA1A cause a rare Mendelian form of
      migraine, familial hemiplegic migraine type 1 (FHM1). Contribution of CACNA1A
      locus has also been studied in the common forms of migraine, migraine with (MA)
      and without aura (MO), but the results have been contradictory. The role of INSR
      is less well established: A region on 19p13 separate from CACNA1A was recently
      reported to be a major locus for migraine and subsequently, the INSR gene was
      associated with MA and MO. Our aim was to clarify the role of these loci in MA
      families by analyzing 72 multigenerational Finnish MA families, the largest
      family sample so far. We hypothesized that the potential major contribution of
      the 19p13 loci should be detected in a family sample of this size, and this was
      confirmed by simulations. We genotyped eight polymorphic microsatellite markers
      surrounding the INSR and CACNA1A genes on 757 individuals. Using parametric and
      non-parametric linkage analysis, none of the studied markers showed any evidence
      of linkage to MA either under locus homogeneity or heterogeneity. However,
      marginally positive lod scores were observed in three families, and thus for
      these families the results remain inconclusive. The overall conclusion is that
      our study did not provide evidence of a major MA susceptibility region on 19p13
      and thus we were not able to replicate the INSR locus finding.

PMID- 15449252
TI  - Analysis of photopolymerization behavior of UDMA/TEGDMA resin mixture and its
      composite by differential scanning calorimetry.
AB  - The aim of this study was to investigate the extent of polymerization (Ep) in
      terms of polymerization rate of UDMA/TEGDMA resin mixtures and its composite
      resin, by using a differential scanning calorimeter (DSC) technique employing a
      photopolymerization apparatus. The resin mixtures used in this study consisted of
      urethane dimethacrylate (UDMA) as a base monomer and triethyleneglycol
      dimethacrylate (TEGDMA) as a low viscosity monomer. The concentration of TEGDMA
      in the mixed monomer was varied to 0, 20, 40, 60, 80, and 100 mol %.
      Additionally, using a base monomer consisting of 60 mol % UDMA and 40 mol %
      TEGDMA, four kinds of composites with silica filler of 0, 20, 40, 60, and 70 wt
      %, were prepared in this study. The general reaction profile and Ep values were
      obtained from the DSC curves. Increasing the concentration of TEGDMA resulted in
      a decrease in the viscosity of the UDMA/TEGDMA mixture, a delay in the time to
      maximum polymerization rate, and an increase in the Ep values of the resin
      mixtures. Furthermore, Ep values decreased with increasing filler content between
      0 and 60 wt % but did not decrease further between 60 and 70 wt %.

PMID- 15449253
TI  - Does endotoxin contribute to aseptic loosening of orthopedic implants?
AB  - Aseptic loosening of orthopedic implants caused by wear particles is a major
      clinical problem. This review examines the hypothesis that bacterial endotoxin
      contributes to aseptic loosening. Clinical findings support this hypothesis:
      bacterial biofilms exist on many implants from patients with aseptic loosening
      and antibiotics in bone cement reduce the rate of aseptic loosening. Three
      approaches were used to demonstrate that adherent endotoxin increases bioactivity
      of titanium particles. These experiments measured cytokine production and
      osteoclast differentiation in vitro and murine calvarial osteolysis in vivo.
      First, removal of >99.9% of the adherent endotoxin from titanium particles
      significantly ablates their biological activity. Second, adding
      lipopolysaccharide back to these "endotoxin-free" particles restores their
      biological activity. Third, cells or mice that are genetically hyporesponsive to
      endotoxin are significantly less responsive to titanium particles than are wild
      type controls. Other investigators have confirmed and extended these results to
      include virtually all orthopedically relevant types of particles, including
      authentic titanium alloy particles retrieved from patients with loosening. Our
      recent studies suggest that adherent endotoxin on orthopedic implants may also
      inhibit initial osseointegration of the implants. Taken together, these studies
      suggest that bacterial endotoxin may have a significant role in induction of
      aseptic loosening.

PMID- 15449254
TI  - Characteristics of titanium-coated polyester prostheses in the animal model.
AB  - Commercially available polyester vascular prostheses (n = 6) in the control group
      (CG) and titanium-coated vascular prostheses (TP; n = 7) were interposed within
      the infrarenal aorta of pigs. The respective healing characteristics and patency
      rates were compared after 3 months. For evaluation purposes, macroscopic,
      histological, and immunohistochemical criteria were applied. The macroscopic
      evaluation revealed complete healing of the TP in comparison with the CG.
      Extraluminal inspection revealed prominent firm cicatricial tissue in the
      prosthesis bed of the TP group. All TP were occluded. In the CG, occlusion of the
      prostheses occurred in n = 1 (16 %). On average, neointimal hyperplasia (NIH) in
      the proximal part of the anastomosis was not significantly different to the CG.
      The extraluminal proliferation index (Ki67) was reduced in the TP group (p =
      0.002). The immunohistochemical analysis of intraluminal changes revealed no
      significant differences between CG and TP. All of the titanium-coated polyester
      vascular prostheses were found to be occluded. The additional coating of
      polyester prostheses with titanium would not appear to be of any particular
      benefit.

PMID- 15449255
TI  - Poly(lactic-co-glycolic acid) microspheres as a potential bulking agent for
      urological injection therapy: preliminary results.
AB  - Injection of bulking substances has been introduced as a new therapy to treat
      urinary incontinence and vesicoureteral reflux. Currently available bulking
      substances for the injection therapies include liquid or particulated silicone,
      collagen gel, and polytetrafluoroethylene paste. However, these materials have
      shown shortcomings such as inflammation, rapid volume decrease, and particle
      migration to distant organs. In the present study, we evaluated poly(lactic-co
      glycolic acid) (PLGA) microspheres as a potential injectable bulking agent for
      the injection therapies. PLGA microspheres (52 microm in average diameter) were
      injectable through various gauges of needles, as the injected microspheres showed
      no tendency to obstruct the needles and microsphere size exclusion was not
      observed upon injection through the needles. After injection of PLGA microspheres
      into the subcutaneous dorsum of mice, inflammation, new tissue volume change, and
      microsphere migration were examined. Host cells from the surrounding tissues
      migrated to the implanted microspheres and formed new hybrid tissue structures.
      The volume of the newly generated tissues was maintained approximately constant
      for 7 weeks. Histological analyses showed no evidence of migration of the
      implanted microspheres to the distant organs. In summary, PLGA microspheres were
      injectable and able to induce a new hybrid tissue formation without initial
      volume decrease or particle migration. These preliminary results suggest that
      this material may be a potentially useful bulking agent for urological injection
      therapies.

PMID- 15449256
TI  - Effects on instruments of the World Health Organization--recommended protocols
      for decontamination after possible exposure to transmissible spongiform
      encephalopathy-contaminated tissue.
AB  - It has been recommended by the World Health Organization (WHO) and Centers for
      Disease Control and Prevention (CDC) that rigorous decontamination protocols be
      used on surgical instruments that have been exposed to tissue possibly
      contaminated with Creutzfeldt-Jakob disease (CJD). This study was designed to
      examine the effects of these protocols on various types of surgical instruments.
      The most important conclusions are: (1) autoclaving in 1N NaOH will cause
      darkening of some instruments; (2) soaking in 1N NaOH at room temperature damages
      carbon steel but not stainless steel or titanium; (3) soaking in chlorine bleach
      will badly corrode gold-plated instruments and will damage some, but not all,
      stainless-steel instruments, especially welded and soldered joints. Damage became
      apparent after the first exposure and therefore long tests are not necessary to
      establish which instruments will be damaged.

PMID- 15449257
TI  - Evidence-based surgery.

PMID- 15449258
TI  - Gene transfer in wound healing.

PMID- 15449259
TI  - Damage control in the abdomen and beyond.
AB  - BACKGROUND: Damage control is not a modern concept, but the application of this
      approach represents a new paradigm in surgery, borne out of a need to care for
      patients sustaining multiple high-energy injuries. METHODS: A Medline search was
      performed to locate English language articles relating to damage control
      procedures in trauma patients. The retrieved articles were manually cross
      referenced, and additional academic and historical articles were identified.
      RESULTS AND CONCLUSION: Damage control surgery, sometimes known as 'damage
      limitation surgery' or 'abbreviated laparotomy', is best defined as creating a
      stable anatomical environment to prevent the patient from progressing to an
      unsalvageable metabolic state. Patients are more likely to die from metabolic
      failure than from failure to complete organ repairs. It is with this awareness
      that damage control surgery is performed, enabling the patient to maintain a
      sustainable physiological envelope.

PMID- 15449260
TI  - Intra-abdominal hypertension and the abdominal compartment syndrome.
AB  - BACKGROUND: Abdominal compartment syndrome (ACS) occurs when intra-abdominal
      pressure is abnormally high in association with organ dysfunction. It tends to
      have a poor outcome, even when treated promptly by abdominal decompression.
      METHODS: A search of the Medline database was performed to identify articles
      related to intra-abdominal hypertension and ACS. RESULTS: Currently there is no
      agreed definition or management of ACS. However, it is suggested that intra
      abdominal pressure should be measured in patients at risk, with values above 20
      mmHg being considered abnormal in most. Abdominal decompression should be
      considered in patients with rising pressure and organ dysfunction, indicated by
      increased airway pressure, reduced cardiac output and oliguria. Organ dysfunction
      often occurs at an intra-abdominal pressure greater than 35 mmHg and may start to
      develop between 26 and 35 mmHg. The mean survival rate of patients affected by
      compartment syndrome is 53 per cent. CONCLUSION: The optimal time for
      intervention is not known, but outcome is often poor, even after decompression.
      Most of the available information relates to victims of trauma rather than
      general surgical patients.

PMID- 15449261
TI  - Meta-analysis of short-term outcomes after laparoscopic resection for colorectal
      cancer.
AB  - BACKGROUND: The safety and efficacy of laparoscopic resection (LR) for colorectal
      cancer remains to be established. METHODS: A meta-analysis of randomized clinical
      trials comparing the short-term outcomes of laparoscopic with those of open
      resection for colorectal cancer was undertaken. A literature search was performed
      for relevant articles published by the end of 2002. Two reviewers independently
      appraised the trials using a predetermined protocol. Results were analysed using
      Comprehensive Meta-analysis. RESULTS: The outcomes of 2512 procedures from 12
      trials were analysed. LR took on average 32.9 per cent longer to perform than
      open resection but was associated with lower morbidity rates. Specifically, wound
      infection rates were significantly lower (odds ratio 0.47 (95 per cent confidence
      interval 0.28 to 0.80); P = 0.005). In patients undergoing LR, the average time
      to passage of first flatus was reduced by 33.5 per cent, that to tolerance of a
      solid diet by 23.9 per cent and that to 80 per cent recovery of peak expiratory
      flow by 44.3 per cent. Early narcotic analgesia requirements were also reduced by
      36.9 per cent, pain at rest by 34.8 per cent and during coughing by 33.9 per
      cent, and hospital stay by 20.6 per cent. There were no significant differences
      in perioperative mortality or oncological clearance. CONCLUSION: LR for
      colorectal cancer is associated with lower morbidity, less pain, a faster
      recovery and a shorter hospital stay than open resection, without compromising
      oncological clearance.

PMID- 15449262
TI  - Meta-analysis of randomized clinical trials of colorectal surgery with or without
      mechanical bowel preparation.
AB  - BACKGROUND: Mechanical bowel preparation is used routinely before colorectal
      surgery, but some randomized clinical trials have suggested that it is of no
      benefit. This study assesses whether such bowel preparation may safely be omitted
      before elective colorectal surgery. METHODS: A search of the literature was
      performed; the inclusion criteria were randomized clinical trials comparing bowel
      preparation with no preparation in colorectal surgery. The methodological quality
      of included trials was assessed. The primary outcome was anastomotic leakage;
      secondary outcomes were other septic complications. The meta-analysis was
      conducted using the Peto one-step method. RESULTS: Eleven trials were retrieved,
      of which seven, containing 1454 patients, were included in the meta-analysis.
      There was no heterogeneity between the trials. Significantly more anastomotic
      leakage was found after mechanical bowel preparation (5.6 versus 3.2 per cent;
      odds ratio 1.75 (95 per cent confidence interval 1.05 to 2.90); P = 0.032). All
      other endpoints (wound infection, other septic complications and non-septic
      complications) also favoured the no-preparation regimen, but the differences were
      not statistically significant. Sensitivity analysis showed that these results
      were similar when trials of poor quality were excluded. Subgroup analysis showed
      that anastomotic leakage was significantly greater after bowel preparation with
      polyethylene glycol (PEG) compared with no preparation, but not after other types
      of preparation. CONCLUSION: There is good evidence to suggest that mechanical
      bowel preparation using PEG should be omitted before elective colorectal surgery.
      Other bowel preparations should be evaluated by further large randomized trials.

PMID- 15449263
TI  - Randomized clinical trial comparing conservative and surgical treatment of
      neurogenic faecal incontinence.
AB  - BACKGROUND: The treatment of choice in idiopathic (neurogenic) faecal
      incontinence is controversial. In a randomized study levatorplasty was compared
      with anal plug electrostimulation of the pelvic floor with respect to functional
      outcome and physiological variables. METHODS: Thirty-one patients underwent
      levatorplasty and 28 anal plug electrostimulation of the pelvic floor over 3
      years. The results were evaluated at 3, 12 and 24 months after completion of
      treatment by means of a validated questionnaire and anorectal manometry and
      manovolumetry. RESULTS: Incontinence scores were significantly reduced during the
      entire observation period in both groups (P < 0.001) as was the use of pads (P =
      0.003 to P < 0.001). The proportion of patients reporting improvement in physical
      and social handicap was greater in the levatorplasty group after 3, 12 and 24
      months (P = 0.036 to P < 0.001). No significant changes in physiological
      variables were observed in either group. CONCLUSION: Better results were obtained
      with levatorplasty than with anal plug electrostimulation of the pelvic floor in
      patients with idiopathic (neurogenic) faecal incontinence. Levatorplasty should
      be therefore be considered the treatment of choice for this condition.

PMID- 15449264
TI  - Randomized clinical trial of the effects of immediate enteral nutrition on
      metabolic responses to major colorectal surgery in an enhanced recovery protocol.
AB  - BACKGROUND: The effects of immediate postoperative enteral nutrition on
      postoperative nitrogen balance and insulin resistance were studied in patients
      subjected to an enhanced-recovery protocol. METHODS: Eighteen patients undergoing
      major colorectal surgery in an enhanced-recovery protocol were randomized to
      immediate postoperative enteral feeding for 4 days with either complete or
      hypocaloric nutrition. Nitrogen balance and changes in glucose kinetics,
      substrate utilization (indirect calorimetry) and insulin sensitivity
      (hyperinsulinaemic-euglycaemic clamp) were measured. Values are mean(s.e.m.).
      RESULTS: Mean postoperative urinary nitrogen losses were low (10.7(1.0) versus
      10.5(0.7) g per day for complete versus hypocaloric nutrition) and insulin
      resistance was insignificant (-20(7) versus -27(11) per cent), with no difference
      between groups. Complete enteral feeding was given without hyperglycaemia (blood
      glucose concentration 5.8(0.4) versus 5.0(0.4) mmol/l) and resulted in nitrogen
      balance (+0.1(0.8) versus -12.6(0.6) g nitrogen per day; P < 0.001). CONCLUSION:
      This enhanced-recovery protocol was associated with minimal postoperative insulin
      resistance and nitrogen losses after surgery. Immediate postoperative enteral
      nutrition was provided without hyperglycaemia and resulted in nitrogen balance.

PMID- 15449265
TI  - Increased nitrotyrosine production in patients undergoing abdominal aortic
      aneurysm repair.
AB  - BACKGROUND: Vascular inflammation is implicated in the pathogenesis of
      atherosclerosis and abdominal aortic aneurysm (AAA), and is thought to involve
      reactive species such as the nitric oxide-derived oxidant peroxynitrite. In the
      present study nitrotyrosine was measured as a stable marker of peroxynitrite
      production in vivo. METHODS: Perioperative blood samples were obtained from
      patients undergoing elective open or endovascular repair of an AAA and from
      patients with intermittent claudication, smoking aged-matched controls, non
      smoking aged-matched controls and non-smoking young healthy controls. Plasma
      nitrotyrosine was measured by an enzyme-linked immunosorbent assay. RESULTS: The
      median plasma nitrotyrosine concentration in patients with an AAA (0.46 nmol
      nitrated bovine serum albumin equivalents per mg protein) was significantly
      higher than that in patients with intermittent claudication (0.35 nmol; P =
      0.002), smoking controls (0.36 nmol; P = 0.001), non-smoking controls (0.35 nmol;
      P = 0.002) and young healthy controls (0.27 nmol; P < 0.001). Nitrotyrosine
      concentrations increased during early reperfusion in open AAA repair, but not
      during endovascular repair. AAA exclusion from the circulation reduced levels to
      control values (P = 0.001). CONCLUSION: Patients with an AAA had raised levels of
      circulating nitrated proteins compared with patients with claudication and
      controls, suggesting a greater degree of ongoing inflammation that was not
      related to smoking.

PMID- 15449266
TI  - Interleukin 6 production during abdominal aortic aneurysm repair arises from the
      gastrointestinal tract and not the legs.
AB  - BACKGROUND: Abdominal aortic aneurysm (AAA) repair is associated with a systemic
      inflammatory response. This inflammatory response probably arises as a result of
      an ischaemia-reperfusion injury to the legs and gastrointestinal tract. In this
      study the relative contributions of these areas to the inflammatory response were
      assessed during elective AAA repair. METHODS: Blood was sampled from the femoral
      vein, portal vein and radial artery of 14 patients undergoing elective AAA repair
      at five time points during the procedure. Plasma was snap-frozen for subsequent
      batch analysis of interleukin (IL) 6. RESULTS: The plasma IL-6 concentration rose
      steadily throughout the procedure at all three locations. The increase in plasma
      IL-6 was significantly greater in the portal vein than in the radial artery
      during ischaemia (P = 0.020). The plasma IL-6 concentration was also
      significantly higher in the portal vein than in the femoral vein (P < 0.001) and
      radial artery (P < 0.001) during reperfusion. There were no significant
      differences between radial artery and femoral vein IL-6 levels at any time point.
      CONCLUSION: Ischaemia and reperfusion during AAA repair were associated with a
      marked increase in IL-6 concentration in the portal vein, suggesting that IL-6
      was produced by the gastrointestinal tract.

PMID- 15449267
TI  - Pylorus-preserving pancreaticoduodenectomy for advanced duodenal disease in
      familial adenomatous polyposis.
AB  - BACKGROUND: Although only 5 per cent of patients with familial adenomatous
      polyposis (FAP) die from duodenal cancer, a recent study indicated that the
      mortality rate is much higher in patients with Spigelman stage IV disease. This
      has prompted an increased rate of referral for excisional surgery and an analysis
      of the results. METHODS: Between January 1994 and June 2002, 16 patients with FAP
      (mean age 55 years; eight men) were referred to a single surgeon for pylorus
      preserving pancreaticoduodenal resection for Spigelman stage IV duodenal
      adenomatosis. RESULTS: One patient died from multiple organ failure after
      relaparotomy for haemorrhage and a jejunal perforation; other major complications
      included anastomotic leak (one), primary haemorrhage (one), lymphatic leak (one),
      chylous ascites (one), pulmonary embolus (two) and prolonged delayed gastric
      emptying that required total parenteral nutrition (three). Overall there were 11
      major complications in eight patients. Two patients developed insulin-dependent
      diabetes and one postprandial dumping. Postoperative histological examination
      revealed five unsuspected cancers, which led to four deaths within 3 years of
      surgery. One patient died 2 months after surgery from pulmonary thromboembolism
      and another at 5 months from an inoperable brain tumour. Nine of the 16 patients
      were alive and well at a mean of 38 months after surgery. CONCLUSION: The choice
      between continued endoscopic surveillance and excisional surgery for Spigelman
      stage IV duodenal disease remains finely balanced.

PMID- 15449268
TI  - Contrast-enhanced ultrasonography during liver surgery.

PMID- 15449269
TI  - Treatment of peritoneal carcinomatosis from adenocarcinoid of appendiceal origin.
AB  - BACKGROUND: Mucinous peritoneal carcinomatosis arising from appendiceal
      adenocarcinoid is uncommon and treatment options have been poorly defined. This
      study examined the effect of combined cytoreductive surgery and intraperitoneal
      chemotherapy on survival in these patients. METHODS: Of 810 patients with
      peritoneal malignancy of appendiceal origin treated by cytoreductive surgery and
      intraperitoneal chemotherapy, 22 patients (mean age 45 years; 17 women) had
      adenocarcinoid. RESULTS: The overall median survival was 18.5 (range 3.2-95.1)
      months, with 2- and 5-year survival rates of 39 and 25 per cent respectively.
      Survival after combined surgery and chemotherapy depended on the Peritoneal
      Cancer Index (P = 0.008) and the extent of cytoreduction (P = 0.007). CONCLUSION:
      Peritoneal carcinomatosis from adenocarcinoid of appendiceal origin is as
      invasive as peritoneal surface malignancy from colorectal adenocarcinoma.
      Patients in whom complete or near-complete surgical removal is possible should be
      considered for cytoreduction in combination with intraperitoneal chemotherapy.

PMID- 15449270
TI  - Development of a dedicated risk-adjustment scoring system for colorectal surgery
      (colorectal POSSUM).
AB  - BACKGROUND: The aim of the study was to develop a dedicated colorectal
      Physiological and Operative Severity Score for the enUmeration of Mortality and
      morbidity (CR-POSSUM) equation for predicting operative mortality, and to compare
      its performance with the Portsmouth (P)-POSSUM model. METHODS: Data were
      collected prospectively from 6883 patients undergoing colorectal surgery in 15 UK
      hospitals between 1993 and 2001. After excluding missing data and 93 patients who
      did not satisfy the inclusion criteria, 4632 patients (68.2 per cent) underwent
      elective surgery and 2107 had an emergency operation (31.0 per cent); 2437
      operations (35.9 per cent) for malignant and 4267 (62.8 per cent) for non
      malignant diseases were scored. Stepwise logistic regression analysis was used to
      develop an age-adjusted POSSUM model and a dedicated CR-POSSUM model. A 60:40 per
      cent split-sample validation technique was adopted for model development and
      testing. Observed and expected mortality rates were compared. RESULTS: The
      operative mortality rate for the series was 5.7 per cent (387 of 6790 patients)
      (elective operations 2.8 per cent; emergency surgery 12.0 per cent). The CR
      POSSUM, age-adjusted POSSUM and P-POSSUM models had similar areas under the
      receiver-operator characteristic curves. Model calibration was similar for CR
      POSSUM and age-adjusted POSSUM models, and superior to that for the P-POSSUM
      model. The CR-POSSUM model offered the best overall accuracy, with an observed :
      expected ratio of 1.000, 0.998 and 0.911 respectively (test population).
      CONCLUSION: The CR-POSSUM model provided an accurate predictor of operative
      mortality. External validation is required in hospitals different from those in
      which the model was developed.

PMID- 15449271
TI  - Surgical management of primary anorectal melanoma.
AB  - BACKGROUND: This aim of this study was to analyse outcome after surgery for
      primary anorectal melanoma and to determine factors predictive of survival.
      METHODS: Records of 40 patients treated between 1977 and 2002 were reviewed.
      RESULTS: Twelve men and 28 women of mean age 58.1 (range 37-83) years were
      included in the analysis. Overall and disease-free survival rates were 17 and 14
      per cent at 5 years. Median overall survival was 17 months and disease-free
      survival was 10 months. The 5-year survival rate was 24 per cent for patients
      with stage I tumours, and zero for those with stage II or stage III disease.
      There was no significant difference in overall survival after wide local excision
      (49 and 16 per cent at 2 and 5 years respectively) and abdominoperineal resection
      (33 per cent at both time points). In patients with stage I and stage II disease,
      there was a significant association between poor survival and duration of
      symptoms (more than 3 months), inguinal lymph node involvement, tumour stage and
      presence of amelanotic melanoma. CONCLUSION: Anorectal melanoma is a rare disease
      with a poor prognosis. Wide local excision is recommended as primary therapy if
      negative resection margins can be achieved.

PMID- 15449272
TI  - Economic impact of laparoscopic versus open abdominal rectopexy.
AB  - BACKGROUND: The introduction of new laparoscopic techniques has important cost
      implications. The aim of this study was to compare the cost effectiveness of
      laparoscopic rectopexy with that of open abdominal rectopexy for full-thickness
      rectal prolapse. METHODS: A cost effectiveness study was conducted alongside a
      randomized trial of laparoscopic versus open abdominal rectopexy. RESULTS: The
      efficacy trial demonstrated significant subjective and objective differences in
      favour of the laparoscopic technique. The mean operating time was 51 min longer
      for laparoscopic rectopexy than for the open procedure. Laparoscopic disposables
      incurred a mean cost of pound 291 per patient. The mean duration of hospital stay
      was significantly shorter for the laparoscopic group (P = 0.001). Laparoscopic
      rectopexy was associated with an overall mean cost saving of pound 357 (95 per
      cent confidence interval pound 164 to pound 592; P = 0.042) per patient.
      CONCLUSION: Laparoscopic rectopexy is associated with superior clinical outcomes
      and is cheaper than the open approach.

PMID- 15449273
TI  - Bisphosphonate-ciprofloxacin bound to Skelite is a prototype for enhancing
      experimental local antibiotic delivery to injured bone.
AB  - BACKGROUND: The risk of osteomyelitis after open bone fracture may be reduced by
      locally applied antibiotics. ENC-41-HP (E41), which comprises ciprofloxacin
      linked to a 'bone seeking' bisphosphonate, loaded on to carrier Skelite calcium
      phosphate granules (E41-Skelite) has favourable in vitro characteristics for
      application to wounded bone. This study assessed E41-Skelite in a rat model of
      acute tibial osteomyelitis. METHODS: Mechanically induced tibial troughs were
      contaminated with approximately log10 4 colony forming units (c.f.u.) of
      Staphylococcus aureus (Cowan 1 strain) 'resistant' to E41 (minimum inhibitory
      concentration 8-16 microg/ml), lavaged and packed with Skelite alone, or with E41
      Skelite slurry. Animals were killed at 24 h (n = 62), 72 h (n = 46) or 14 days (n
      = 12), and each tibia was assessed for S. aureus load (c.f.u./g tibia) and
      histological appearance (14 days only). RESULTS: At 24 and 72 h, the tibias of
      rats treated with E41-Skelite (n = 54) had a significantly lower mean (s.e.m.)
      load of S. aureus than animals that received Skelite alone (n = 54): log10
      3.6(0.2) versus 6.4(0.1) c.f.u./g respectively at 24 h (P < 0.001, Mann-Whitney
      rank sum test) and log10 4.4(0.2) versus 6.6(0.1) c.f.u./g at 72 h (P < 0.001).
      At 14 days, E41-Skelite-treated tibias had fewer bacteria, no signs of
      osteomyelitis and histological signs of healing. CONCLUSION: E41-Skelite, a
      prototype granulated topical antibiotic delivery system, reduced the development
      of infection in experimental bone wounds.

PMID- 15449274
TI  - Prognostic value of age and sex in early gastric cancer.
AB  - BACKGROUND: The need for lymph node dissection in early gastric cancer (EGC) is
      controversial. The present study investigated the possibility of planning
      treatment for EGC according to age and sex rather than node status. METHODS:
      Overall survival rate and cause of death were analysed according to age (5-year
      increments) and sex in 4231 patients with EGC. Cox proportional hazard regression
      analyses were used to identify the most valuable predictor. RESULTS: In patients
      with EGC 5- and 10-year cancer-specific survival rates were 98.4 and 96.3 per
      cent respectively, whereas corresponding overall survival rates were 90.2 and
      80.9 per cent. The critical age for determining prognosis was 70 years for men
      (chi2 = 131.34, P < 0.001) and 75 years for women (chi2 = 64.35, P < 0.001). For
      both sexes, the 10-year overall survival rate was less than 30 per cent in
      patients over 80 years old. Multivariate Cox stepwise regression analysis
      identified age as the most powerful prognostic indicator in EGC. The rate of
      death from causes unrelated to the tumour increased significantly with age,
      whereas that from recurrence was not affected by age. CONCLUSION: Age is a better
      prognostic indicator than node status in both men and women with EGC. Age and sex
      should be taken into account as well as conventional clinicopathological
      variables related to lymph node metastases when determining appropriate therapy
      for EGC.

PMID- 15449275
TI  - Randomized clinical trial of the costs of open and laparoscopic surgery for
      colonic cancer (Br J Surg 2004; 91: 409-417).

PMID- 15449276
TI  - Optimal total mesorectal excision for rectal cancer is by dissection in front of
      Denonvilliers' fascia (Br J Surg 2004; 91: 121-123).

PMID- 15449277
TI  - Incidence and outcome of surgical repair of spigelian hernia (Br J Surg 2004; 91:
      640-644).

PMID- 15449278
TI  - Fistuloclysis can successfully replace parenteral feeding in the nutritional
      support of patients with enterocutaneous fistula (Br J Surg 2004; 91: 625-631).

PMID- 15449291
TI  - Metabolic engineering of isoprenoid biosynthesis in Arabidopsis for the
      production of taxadiene, the first committed precursor of Taxol.
AB  - Paclitaxel (Taxol) is a widely used anticancer isoprenoid produced by the
      secondary metabolism of yew (Taxus sp.) trees. However, only limited amounts of
      Taxol or related metabolites (taxoids) can be obtained from the currently
      available sources. In this work we have taken the first step toward genetically
      engineering the biosynthesis of taxoids in angiosperms. The first committed step
      in Taxol biosynthesis is the production of taxadiene from geranylgeranyl
      diphosphate (GGPP), catalyzed by the plastid-localized enzyme taxadiene synthase
      (TXS). A recombinant T. baccata TXS lacking the putative plastid targeting
      peptide and fused to a C-terminal histidine (His) tag was shown to be
      enzymatically active in Escherichia coli. Constitutive production of the full
      length His-tagged enzyme in Arabidopsis thaliana plants led to the accumulation
      of taxadiene and concomitant growth retardation and decreased levels of
      photosynthetic pigment in transgenic plants. Although these phenotypes may derive
      from a toxic effect of taxadiene, the lower accumulation of endogenous plastid
      isoprenoid products such as carotenoids and chlorophylls in transgenic plants
      also suggests that the constitutive production of an active TXS enzyme might
      alter the balance of the GGPP pool. Induction of transgene expression using a
      glucocorticoid-mediated system consistently resulted in a more efficient
      recruitment of GGPP for the production of taxadiene, which reached levels 30-fold
      higher than those in plants constitutively expressing the transgene. This
      accomplishment illustrates the possibility of engineering the production of
      taxoids and other GGPP-derived isoprenoids in crop plants despite the constraints
      associated with limited knowledge with regard to regulation of GGPP availability.

PMID- 15449292
TI  - Characterization of a continuous supermacroporous monolithic matrix for
      chromatographic separation of large bioparticles.
AB  - A continuous supermacroporous monolithic chromatographic matrix has been
      characterized using a capillary model, experimental breakthrough curves, and
      pressure drop experiments. The model describes the convective flow and its
      dispersive mixing effects, mass transfer resistance, pore size distribution, and
      the adsorption behavior of the monolithic matrix. It is possible to determine an
      effective pore size distribution by fitting the capillary model to experimental
      breakthrough curves and pressure drop experiments. The model is able to describe
      the flow rate dependence of the experimental breakthrough curves. Mass transport
      resistance was due to: (i) dispersive mixing effects in the convective flow in
      the pores; and (ii) slow diffusion in the stagnant film covering the surface
      within each pore, under adsorption conditions. The monolithic matrix can be
      described by a very narrow pore size distribution, illustrating one of the
      advantages of the gel. A broader pore size distribution results in increased band
      broadening. This can be studied easily using the model developed in this
      investigation.

PMID- 15449293
TI  - Analysis of in vivo kinetics of glycolysis in aerobic Saccharomyces cerevisiae by
      application of glucose and ethanol pulses.
AB  - This article presents the dynamic responses of several intra- and extracellular
      components of an aerobic, glucose-limited chemostat culture of Saccharomyces
      cerevisiae to glucose and ethanol pulses within a time window of 75 sec. Even
      though the ethanol pulse cannot perturb the glycolytic pathway directly, a
      distinct response of the metabolites at the lower part of glycolysis was found.
      We suggest that this response is an indirect effect, caused by perturbation of
      the NAD/NADH ratio, which is a direct consequence of the conversion of ethanol
      into acetaldehyde. This effect of the NAD/NADH ratio on glycolysis might serve as
      an additional explanation for the observed decrease of 3PG, 2PG, and PEP during a
      glucose pulse. The responses measured during the ethanol pulse were used to
      evaluate the allosteric regulation of glycolysis. Our results confirm that FBP
      stimulates pyruvate kinase and suggest that this effect is pronounced.
      Furthermore, it appears that PEP does not play an important role in the
      allosteric regulation of phosphofructo kinase.

PMID- 15449294
TI  - Model-based optimization of a conductive matrix enzyme electrode.
AB  - A mathematical model has been developed to describe the mechanism for internal
      mass transfer and enzyme reaction kinetics of an amperometric conductive matrix
      enzyme electrode. The model is simplified and solved analytically to arrive at a
      representation for the response slope in the linear range as well as for the
      response time. This is the first time that the response time of an enzyme
      electrode is described by a mathematical model. Simulations give information on
      how the design parameters influence the performance of the electrode for a
      glucose oxidase catalyzed sensing reaction process. Based on this information,
      several designs were constructed and tested showing suitable agreement with
      theoretical predictions. Finally, an optimized electrode was designed and
      validated.

PMID- 15449295
TI  - Heterogeneous conditions in dissolved oxygen affect N-glycosylation but not
      productivity of a monoclonal antibody in hybridoma cultures.
AB  - It is known that heterogeneous conditions exist in large-scale animal cell
      cultures. However, little is known about how heterogeneities affect cells,
      productivities, and product quality. To study the effect of non-constant
      dissolved oxygen tension (DOT), hybridomas were subjected to sinusoidal DOT
      oscillations in a one-compartment scale-down simulator. Oscillations were forced
      by manipulating the inlet oxygen partial pressure through a feedback control
      algorithm in a 220-mL bioreactor maintained at a constant agitation. Such
      temporal DOT oscillations simulate spatial DOT gradients that can occur in large
      scales. Different oscillation periods, in the range of 800 to 12,800 s (axis of
      7% (air saturation) and amplitude of 7%), were tested and compared to constant
      DOT (10%) control cultures. Oscillating DOT decreased maximum cell
      concentrations, cell growth rates, and viability indexes. Cultures at oscillating
      DOT had an increased glycolytic metabolism that was evidenced by a decrease in
      yield of cells on glucose and an increase in lactate yield. DOT gradients, even
      several orders of magnitude higher than those expected under practical large
      scale conditions, did not significantly affect the maximum concentration of an
      IgG(1) monoclonal antibody (MAb). The glycosylation profile of the MAb produced
      at a constant DOT of 10% was similar to that reported in the literature. However,
      MAb produced under oscillating culture conditions had a higher amount of
      triantennary and sialylated glycans, which can interfere with effector functions
      of the antibody. It was shown that transient excursions of hybridomas to limiting
      DOT, as occurs in deficiently mixed large-scale bioreactors, is important to
      culture performance as the oscillation period, and thus the time cells spent at
      low DOT, affected cell growth, metabolism, and the glycosylation pattern of MAb.
      Such results underline the importance of monitoring protein characteristics for
      the development of large-scale processes.

PMID- 15449296
TI  - Trickle-bed root culture bioreactor design and scale-up: growth, fluid-dynamics,
      and oxygen mass transfer.
AB  - Trickle-bed root culture reactors are shown to achieve tissue concentrations as
      high as 36 g DW/L (752 g FW/L) at a scale of 14 L. Root growth rate in a 1.6-L
      reactor configuration with improved operational conditions is shown to be
      indistinguishable from the laboratory-scale benchmark, the shaker flask (mu=0.33
      day(-1)). These results demonstrate that trickle-bed reactor systems can sustain
      tissue concentrations, growth rates and volumetric biomass productivities
      substantially higher than other reported bioreactor configurations. Mass transfer
      and fluid dynamics are characterized in trickle-bed root reactors to identify
      appropriate operating conditions and scale-up criteria. Root tissue respiration
      goes through a minimum with increasing liquid flow, which is qualitatively
      consistent with traditional trickle-bed performance. However, liquid hold-up is
      much higher than traditional trickle-beds and alternative correlations based on
      liquid hold-up per unit tissue mass are required to account for large changes in
      biomass volume fraction. Bioreactor characterization is sufficient to carry out
      preliminary design calculations that indicate scale-up feasibility to at least
      10,000 liters.

PMID- 15449297
TI  - Physicochemical studies of cadmium(II) biosorption by the invasive alga in
      Europe, Sargassum muticum.
AB  - In recent years, there has been a significant increase in the studies concerning
      brown seaweed as biosorbents for metal removal owing to their high binding
      ability and low cost. This work reports the results of a study regarding the
      cadmium binding equilibria of dead biomass from the seaweed Sargassum muticum;
      this alga is a pest fouling organism that competes with the local fucalean
      species and may also interfere with the "sea industry"; therefore, it would
      constitute an ideal material to be used as biosorbent. Seven different treatments
      were tested in order to obtain a stable biomass that could be suitable for
      industrial use under a broad range of operational conditions. The treatments
      employed were protonation, chemical cross-linking with formaldehyde, KOH,
      Ca(OH)(2) and CaCl(2) or physical treatments with acetone and methanol. The
      equilibrium adsorption isotherms of Langmuir, Freundlich, and Langmuir-Freundlich
      were obtained for the quantitative description of the cadmium uptake. The effect
      of pH on biosorption equilibrium was studied at values ranging from 1 to 6,
      demonstrating the importance of this parameter for an accurate evaluation of the
      biosorption process. Maximum biosorption was found pH higher than 4.5. The
      maximum biosorption uptake for the raw biomass was 65 mg g(-1), while for
      formaldehyde cross-linking biomass the uptake increases to 99 mg g(-1) and for
      protonated biomass to 95 mg g(-1). Potentiometric titrations were carried out to
      estimate the total number of weak acid groups and to obtain their apparent pK
      value, 3.85, using the Katchalsky model. Kinetic studies varying cadmium
      concentration, algal dose, and ionic strength were carried out. Over 95% of the
      maximum cadmium uptake was achieved within 45 min, so the process can be
      considered relatively fast. A pseudo-second-order model, for the kinetics of
      cadmium biosorption, was shown to be able to reproduce experimental data points
      with accuracy.

PMID- 15449298
TI  - Stochastic modeling of the phase-variable pap operon regulation in uropathogenic
      Escherichia coli.
AB  - Regulation of the pap operon in uropathogenic Escherichia coli is phase variable.
      This phase variation arises from competition between regulatory proteins at two
      sites within the regulatory region, GATC(dist) and GATC(prox). We have used the
      available literature data to design a stochastic model of the molecular
      interactions of pap regulation and expression during growth in a non-glucose
      environment at 37 degrees C. The resulting wild-type model is consistent with
      reported data. The wild-type model served as a basis for two "in silico" mutant
      models for investigating the role of key regulatory components, the GATC(dist)
      binding site and the PapI interaction with Lrp at the GATC(prox) site. Our
      results show that competition at GATC(dist) is required for phase variation, as
      previously reported. However, our results suggest that removal of competition at
      GATC(dist) does not affect initial state dependence. Additionally, the PapI
      involvement in Lrp translocation from GATC(prox) to GATC(dist) is required for
      the initial state dependence but not for phase variation. Our results also
      predict that pap expression is maximized at low growth rates and minimized at
      high growth rates. These predictions provide a basis for further experimental
      investigation.

PMID- 15449299
TI  - Energy-efficient growth of phage Q Beta in Escherichia coli.
AB  - The role of natural selection in the optimal design of organisms is
      controversial. Optimal forms, functions, or behaviors of organisms have long been
      claimed without knowledge of how genotype contributes to phenotype, delineation
      of design constraints, or reference to alternative designs. Moreover, arguments
      for optimal designs have been often based on models that were difficult, if not
      impossible, to test. Here, we begin to address these issues by developing and
      probing a kinetic model for the intracellular growth of bacteriophage Q beta in
      Escherichia coli. The model accounts for the energetic costs of all template
      dependent polymerization reactions, in ATP equivalents, including RNA-dependent
      RNA elongation by the phage replicase and synthesis of all phage proteins by the
      translation machinery of the E. coli host cell. We found that translation
      dominated phage growth, requiring 85% of the total energy expenditure. Only 10%
      of the total energy was applied to activities other than the direct synthesis of
      progeny phage components, reflecting primarily the cost of making the negative
      strand RNA template that is needed for replication of phage genomic RNA. Further,
      we defined an energy efficiency of phage growth and showed its direct
      relationship to the yield of phage progeny. Finally, we performed a sensitivity
      analysis and found that the growth of wild-type phage was optimized for progeny
      yield or energy efficiency, suggesting that phage Q beta has evolved to optimally
      utilize the finite resources of its host cells.

PMID- 15449300
TI  - Effects of humic substances and soya lecithin on the aerobic bioremediation of a
      soil historically contaminated by polycyclic aromatic hydrocarbons (PAHs).
AB  - The high hydrophobicity of polycyclic aromatic hydrocarbons (PAHs) strongly
      reduces their bioavailability in aged contaminated soils, thus limiting their
      bioremediation. The biodegradation of PAHs in soils can be enhanced by employing
      surface-active agents. However, chemical surfactants are often recalcitrant and
      exert toxic effects in the amended soils. The effects of two biogenic materials
      as pollutant-mobilizing agents on the aerobic bioremediation of an aged
      contaminated soil were investigated here. A soil historically contaminated by
      about 13 g kg(-1) of a large variety of PAHs, was amended with soya lecithin (SL)
      or humic substances (HS) at 1.5% w/w and incubated in aerobic solid-phase and
      slurry-phase reactors for 150 days. A slow and only partial biodegradation of low
      molecular weight PAHs, along with a moderate depletion of the initial soil
      ecotoxicity, was observed in the control reactors. The overall removal of PAHs in
      the presence of SL or HS was faster and more extensive and accompanied by a
      larger soil detoxification, especially under slurry-phase conditions. The SL and
      HS could be metabolized by soil aerobic microorganisms and enhanced the
      occurrence of both soil PAHs and indigenous aerobic PAH-degrading bacteria in the
      reactor water phase. These results indicate that SL and HS are biodegradable and
      efficiently enhance PAH bioavailability in soil. These natural surfactants
      significantly intensified the aerobic bioremediation of a historically PAH
      contaminated soil under treatment conditions similar to those commonly employed
      in large-scale soil bioremediation.

PMID- 15449301
TI  - Modeling aerobic carbon oxidation and storage by integrating respirometric,
      titrimetric, and off-gas CO2 measurements.
AB  - A method for detailed investigation of aerobic carbon degradation processes by
      microorganisms is presented. The method relies on an integrated use of the
      respirometric, titrimetric, and off-gas CO(2) measurements. The oxygen uptake
      rate (OUR), hydrogen ion production rate (HPR), and the carbon dioxide transfer
      rate (CTR) resulting from the biological as well as physicochemical processes,
      coupled with a metabolic model characterizing both the growth and carbon storage
      processes, enables the comprehensive study of the carbon degradation processes.
      The method allows the formation of carbon storage products and the biomass growth
      rates to be estimated without requiring any off-line biomass or liquid-phase
      measurements, although the practical identifiability of the system could be
      improved with additional measurements. Furthermore, the combined yield for
      biomass growth and carbon storage is identifiable, along with the affinity
      constant with respect to the carbon substrate. However, the individual yields for
      growth and carbon storage are not identifiable without further knowledge about
      the metabolic pathways employed by the microorganisms in the carbon conversion.
      This is true even when more process variables are measured. The method is applied
      to the aerobic carbon substrate degradation by a full-scale sludge using acetate
      as an example carbon source. The sludge was able to quickly take up the substrate
      and store it as poly-beta-hydroxybutyrate (PHB). The PHB formation rate was a few
      times faster than the biomass growth rate, which was confirmed by off-line liquid
      and solid-phase analysis. The estimated combined yield for biomass growth and
      carbon storage compared closely to that determined from the theoretical yields
      reported in literature based on thermodynamics. This suggests that the
      theoretical yields may be used as default parameters for modeling purposes.

PMID- 15449302
TI  - Relation between cell disruption conditions, cell debris particle size, and
      inclusion body release.
AB  - The efficiency of physical separation of inclusion bodies from cell debris is
      related to cell debris size and inclusion body release and both factors should be
      taken into account when designing a process. In this work, cell disruption by
      enzymatic treatment with lysozyme and cellulase, by homogenization, and by
      homogenization with ammonia pretreatment is discussed. These disruption methods
      are compared on the basis of inclusion body release, operating costs, and cell
      debris particle size. The latter was measured with cumulative sedimentation
      analysis in combination with membrane-associated protein quantification by SDS
      PAGE and a spectrophotometric peptidoglycan quantification method. Comparison of
      the results obtained with these two cell debris quantification methods shows that
      enzymatic treatment yields cell debris particles with varying chemical
      composition, while this is not the case with the other disruption methods that
      were investigated. Furthermore, the experiments show that ammonia pretreatment
      with homogenization increases inclusion body release compared to homogenization
      without pretreatment and that this pretreatment may be used to control the cell
      debris size to some extent. The enzymatic disruption process gives a higher
      product release than homogenization with or without ammonia pretreatment at lower
      operating costs, but it also yields a much smaller cell debris size than the
      other disruption process. This is unfavorable for centrifugal inclusion body
      purification in this case, where cell debris is the component going to the
      sediment and the inclusion body is the floating component. Nevertheless,
      calculations show that centrifugal separation of inclusion bodies from the
      enzymatically treated cells gives a high inclusion body yield and purity.

PMID- 15449303
TI  - The place of memantine in the treatment of Alzheimer's disease: a number needed
      to treat analysis.
AB  - INTRODUCTION: Memantine is currently the only treatment approved for moderately
      severe to severe Alzheimer's disease (AD). There is still some discussion as to
      its place in clinical practice and many UK clinicians are discouraged for
      economic reasons from prescribing it. We adopt a 'number needed to treat' (NNT)
      approach to assess the benefits reported in memantine trials. METHOD: We searched
      Medline and the Cochrane Dementia and Cognitive Improvement Specialised Register
      for double-blind, randomised and controlled trials of memantine in AD. If
      efficacy was only reported in terms of mean change, rather than as number of
      individuals who responded or were harmed by an intervention, we contacted the
      drug companies (Merz and Lundbeck) to ask for more data. We also calculated
      effect size. RESULTS: We found two trials of memantine in AD that met our
      criteria. We found that NNTs for global outcome were 3 and 6, for cognitive
      outcome 7 and for activities of daily living 4 and 8. The effect size for
      memantine varied between 0.32 and 0.62. For NNH memantine was no more harmful
      than placebo and significantly less so for the outcome of agitation. CONCLUSION:
      The small NNTs and the lack of harm shown by the NNHs strongly suggest that
      memantine, as with cholinesterase inhibitors, has a valuable place in the current
      clinical management of AD. The effect sizes are mainly in the 'medium' range for
      clinical effect, which also suggests that memantine has a clinical place in terms
      of cognition and dependency. There remains a need for more studies that examine
      carer burden, behavioural and psychological effects, and quality of life for both
      the person with dementia and the caregiver.

PMID- 15449304
TI  - Interrelationships among Atg proteins during autophagy in Saccharomyces
      cerevisiae.
AB  - Macroautophagy is a bulk degradation process induced by nutrient starvation in
      eukaryotic cells. In Saccharomyces cerevisiae, 16 ATG genes are essential for
      autophagosome formation. Recently, we demonstrated that these ATG genes can be
      classified into three groups on the basis of localization of GFP-Atg8p/Aut7p and
      Atg5p/Apg5p-GFP under nutrient-rich conditions. In this study, we analysed the
      intracellular localization of GFP-Atg8p, an autophagosome marker, in atg mutants
      under autophagy-inducing conditions; the localization of GFP-Atg8p exhibited
      several distinct patterns. Subsequent analyses revealed epistatic
      interrelationships among Atg proteins during the process of autophagosome
      formation.

PMID- 15449305
TI  - Kluyveromyces lactis SSO1 and SEB1 genes are functional in Saccharomyces
      cerevisiae and enhance production of secreted proteins when overexpressed.
AB  - The SEB1/SBH1 and the SSO genes encode components of the protein secretory
      machinery functioning at the opposite ends, ER translocation and exocytosis,
      respectively, of the secretory pathway in Saccharomyces cerevisiae.
      Overexpression of these genes can rescue temperature-sensitive (ts) growth defect
      of many sec mutants impaired in protein secretion. Furthermore, their
      overexpression in wild-type yeast enhances production of secreted proteins in S.
      cerevisiae, which suggests that they may be rate-limiting factors in this
      process. Here we report isolation of Kluyveromyces lactis homologues of these
      genes. KlSSO1 and KlSEB1 were isolated as clones capable of rescuing growth of ts
      sso2-1 and seb1Delta seb2Delta sem1Delta strains, respectively, at the
      restrictive temperature. The encoded Kluyveromyces proteins are up to 70%
      identical with the S. cerevisiae homologues at the amino acid level and can
      functionally replace them. Interestingly, KlSSO1 and KlSEB1 show similar
      enhancing effect on production of a secreted protein as the SSO and SEB1 genes of
      S. cerevisiae when overexpressed. In accordance with the high homology level of
      the secretory pathway proteins in different yeast species, the polyclonal
      antibodies raised against S. cerevisiae Seb1p, Sso2p and Sec4p can detect
      homologous proteins in cell lysates of K. lactis and Pichia pastoris, the latter
      also in Candida utilis. The GenBank Accession Nos are AF307983 (K. lactis SSO1)
      and AF318314 (K. lactis SEB1).

PMID- 15449306
TI  - Schizosaccharomyces pombe ER oxidoreductin-like proteins SpEro1a p and SpEro1b p.
AB  - Endoplasmic reticulum oxidoreductins (Ero proteins) are essential for oxidation
      of protein disulphide isomerase (Pdi), which introduces disulphide bonds in
      target proteins. Contrary to the situation in Saccharomyces cerevisiae, with a
      single Ero protein (Ero1p), the genomes of Schizosaccharomyces pombe and of
      humans encode two Ero-like proteins. Here we show that both Sz. pombe proteins
      (SpEro1a p and SpEro1b p) are N-glycosylated and firmly associated with membranes
      of the secretory pathway. Surprisingly, only expression of SpEro1b p completely
      restores growth of the temperature-sensitive S. cerevisiae ero1-1 mutant, whereas
      SpEro1a p only partially complements this mutation. Upon expression in S.
      cerevisiae wild-type cells, SpEro1b p leads to a significantly increased
      resistance to reductive stress by dithiothreitol, whereas SpEro1a p has only a
      marginal effect. These data suggest that SpEro1b p is a functional homologue of
      the S. cerevisiae Ero1p.

PMID- 15449307
TI  - Tandem affinity purification of the Candida albicans septin protein complex.
AB  - A novel vector was constructed to enable the integrative marking of individual
      genes and the affinity purification of interacting molecules within protein
      complexes from Candida albicans using a tandem 6 x histidine and FLAG epitope
      tag. The system was verified by purifying the C. albicans septin complex (a self
      associating complex of cytoskeletal proteins) from both yeast and hyphal cells.
      One-step affinity purification was insufficient for purification of the protein
      complex, whereas tandem affinity purification (TAP) gave an extensively purified
      protein complex with a very low background. Electrophoretic and mass spectrometry
      analysis showed that the affinity-purified C. albicans septin complex, which
      comprises predominantly CaCdc3p, CaCdc10p, CaCdc11p, CaCdc12p and CaSep7p, was
      not affected by cell morphology. The purified septin complex appeared to have a
      stoichiometry of 2 CaCdc3p, 1-2 CaCdc10p, 1 CaCdc11p, 2 CaCdc12p and < or = 1
      CaSep7p. The successful application of TAP to the purification and analysis of
      the C. albicans septin complex indicates that this technology will have much
      wider application to proteomic studies of this pathogenic fungus.

PMID- 15449308
TI  - Expression of the expanded YFL007w ORF and assignment of the gene name BLM10.
AB  - This report assigns a gene name to an extended ORF in Saccharomyces cerevisiae,
      and provides the first evidence from Northern analyses that the ORF is expressed
      and the transcript is the predicted size.

PMID- 15449309
TI  - Chr4, a Schizosaccharomyces pombe homologue of the Saccharomyces cerevisiae
      Chs4p/Skt5p protein, is related to septum formation and is required for the
      proper localization of Chs2.
AB  - In Saccharomyces cerevisiae, Chs4p directly interacts with chitin synthase III
      (Chs3p) to act as a post-translational regulator of the Chs3p complex. We
      identified four Chs4p homologous proteins in Schizosaccharomyces pombe which we
      named Chr1, Chr2, Chr3 and Chr4 (putative chitin synthase regulatory factor). We
      assessed the functions of these proteins and found that while overproduction of
      Chr1, Chr2 or Chr3 did not affect the cellular morphology of wild-type Sz. pombe
      cells, overproduction of Chr4 caused the cells to form multi-septa and delayed
      their growth. All multiple disruptants of chr1, chr2, chr3 and chr4 grew normally
      under a variety of growth conditions. However, while chitin synthase II (Chs2)
      normally localizes exclusively at the septum, in many chr4-disrupted cells it was
      found in the cytoplasm and the septa. Chs2 did localize at the abnormal septa
      caused by the overproduction of chr4+. Chr4-13Myc expression was unaffected by
      the different media or growth conditions in both wild-type and the chs2
      disruptant. Chs2 expression was also unaltered by the absence of Chr4. Moreover,
      Chr4-13Myc localized mostly at the tips and the septum during vegetative growth
      in chs2, chr1, chr2 and chr3 disruptants as well as in wild-type. Thus, chr4+ is
      involved in septum formation and is required for the proper localization of Chs2
      at the septum in Sz. pombe.

PMID- 15449310
TI  - Role of OGG1 and NTG2 in the repair of oxidative DNA damage and mutagenesis
      induced by hydrogen peroxide in Saccharomyces cerevisiae: relationships with
      transition metals iron and copper.
AB  - The base excision repair pathway of Saccharomyces cerevisiae possesses three DNA
      N-glycosylases, viz. Ogg1p, Ngt1p and Ntg2p, involved in the repair of oxidative
      DNA damage. It was previously reported that inactivation of any of these
      activities, in most cases, did not generate a sensitive mutant phenotype to a
      variety of oxidative agents. Only the ntg1 mutant appeared to be more sensitive
      to hydrogen peroxide (H2O2) than a wild-type (WT) strain. In the present study we
      evaluated the role of S. cerevisiae OGG1 and NTG2 genes in the repair of
      oxidative lesions induced by high H2O2 concentrations (5-100 mM for 20 min),
      followed by catalase treatment (500 IU/ml). In these conditions, the ogg1 mutant
      was more sensitive than the WT strain to H2O2 (concentration 40-60 mM).
      Unexpectedly, the inactivation of NTG2 in an ogg1 background was able to suppress
      both sensitivity and mutagenesis induced by H2O2. Indeed, even the ntg2 single
      mutant was more resistant than the WT (60-100 mM H2O2). The use of metal ion
      chelators dipyridyl and neocuproine allowed us to evaluate the participation of
      iron and copper ions in the production of lethal and mutagenic lesions during
      H2O2 treatment in different DNA repair-deficient S. cerevisiae strains. The roles
      of OGG1 and NTG2 genes in the repair of lethal and mutagenic oxidative lesions
      induced by H2O2 and their relationships with iron and copper ions are discussed.

PMID- 15449311
TI  - Cell shape and growth of budding yeast cells in restrictive microenvironments.
AB  - Effects of limited growth space on the cell morphology and cell growth are
      investigated by creating rigid outside environments. The cube-shaped holes big
      enough for a single cell of the budding yeast Saccharomyces cerevisiae were
      prepared with a focused ion-beam (FIB), commonly used for processing
      semiconductors. We demonstrated that the outline of the cells changes their
      ellipsoidal morphology into a cubic form when the daughter cells are grown in the
      holes, indicating that yeast cells change their shape in response to external
      limited space. The yeast cells grown in the microenvironments exhibit neither bud
      formation nor nuclear division. Although restricted growth caused by the physical
      barriers leads to the block of cell cycle progression in the wild-type cells,
      swe1Delta cells defective in the morphogenesis checkpoint become binucleate after
      being grown in the microenvironments. These results suggest that yeast cells
      under spatial restriction arrest cell cycle progression in a Swelp-dependent
      manner.

PMID- 15449312
TI  - Transcriptional activities of mutant p53: when mutations are more than a loss.
AB  - The dominant oncogenic properties of mutant p53 have been recognized as a
      phenomenon associated with tumor progression a long time ago, even before it was
      realized that the major function of wild type p53 is that of a tumor suppressor.
      Recent advances in this fascinating area in tumor cell biology reveal that the
      community of mutant p53 proteins is comprised of proteins that are extremely
      diverse both structurally and functionally, and elicit a multitude of cellular
      responses that not only are entirely distinct from those mediated by wild type
      p53, but also vary among different mutant p53 proteins. Aberrant regulation of
      transcription is one of the mechanisms underlying the ability of some mutant p53
      proteins to act as oncogenic factors. Systematic analyses of the transcriptional
      activities of mutant p53 suggest that not the loss of transcriptional activity as
      such, but alterations of target DNA selectivity may be the driving force of
      mutant p53 specific transcription underlying the growth-promoting effects of
      mutant p53. This article focuses on mechanistic aspects of mutp53 "gain-of
      function" with the emphasis on possible mechanisms underlying transcriptional
      activation by mutp53.

PMID- 15449313
TI  - Inhibition of cell proliferation in human breast tumor cells by antisense
      oligonucleotides against facilitative glucose transporter 5.
AB  - In recent years, successful examples of antisense oligonucleotide (AS) therapy
      for genetic diseases have stimulated scientists to investigate its application on
      cancer diseases. AS can be used to down-regulate the mRNA and protein expression
      by annealing to specific region of the target mRNA which is responsible for the
      malignancy. Glucose transporter 5 (Glut5) is a tissue specific transporter that
      can be found on breast cancer tissues but not on normal breast tissues.
      Therefore, it is of clinical interest to investigate whether AS against Glut5
      mRNA can tackle breast cancer. In this study, two cell lines, MCF-7 which is
      estrogen-receptor positive and MDA-MB-231 which is estrogen-receptor negative,
      were used to mimic breast cancer tissues at early and late stages, respectively.
      A 15-base sequence around the start codon of Glut5 was used. It was found that AS
      against Glut5 exerted anti-proliferative effect on both of these two breast tumor
      cell lines and seemed to exert its effect via the suppression of expression of
      Glut5 proteins in the cells. AS against Glut5 exhibited no effect on human
      hepatoma HepG2 cells which do not possess any Glut5. The results imply an
      alternative way in treating breast tumor as the AS against Glut5, unlike
      tamoxifen, takes effect on breast tumor cells via suppressing the expression of
      Glut5 that they specifically possess, and regardless whether the breast tumors
      are estrogen dependent or not.

PMID- 15449314
TI  - Nuclear pore complex oxalate binding protein p62: its expression on oxalate
      exposure to VERO cells.
AB  - Oxalate rich stones are the most common among the various stones. Oxalate binding
      protein plays a vital role in the transport of oxalate. Nuclear pore complex
      (NPC) contains a protein of molecular weight 62 kDa and it has maximum oxalate
      binding activity. The physiological significance of the presence of oxalate
      binding protein in the NPC is not well understood. In order to study its
      function, the expression of this protein during oxalate stress condition and the
      morphological changes on oxalate exposure to synchronized VERO cells have been
      determined. VERO cells were synchronized at different stages of cell cycle using
      cell cycle blockers and expression of the NPC p62 was assessed using enzyme
      linked immunosorbent assay (ELISA) technique with p62 antibody (MAb 414).
      Expression of NPC p62 was more pronounced in 1.0 mM oxalate concentration in
      mitotic phase than in S phase, suggesting cell cycle dependency. During oxalate
      exposure there is cell aggregation and complete degeneration of cell morphology
      occurs, which in turn lead to the expression of certain genes, including the NPC
      oxalate binding protein p62. Thus, oxalate induces degeneration of cells (may be
      due to the lipid peroxidation) and leads to the expression of NPC oxalate binding
      protein and the expression is of cell cycle dependent manner.

PMID- 15449315
TI  - Zymogen activation and characterization of a major gelatin-cleavage activity
      localized to the sea urchin extraembryonic matrix.
AB  - The hyaline layer (HL) is an apically located extracellular matrix (ECM) which
      surrounds the sea urchin embryo from the time of fertilization until
      metamorphosis occurs. While gelatin-cleavage activities were absent from freshly
      prepared hyaline layers, a dynamic pattern of activities developed in layers
      incubated at 15 or 37 degrees C in Millipore-filtered sea water (MFSW). Cleavage
      activities at 90, 55, 41, and 32 kDa were evident following incubation at either
      temperature. The activation pathway leading to the appearance of these species
      was examined to determine the minimum salt conditions required for processing and
      to establish precursor-product relationships. In both qualitative and
      quantitative assays, the purified 55 kDa gelatinase activity was inhibited by
      1,10-phenanthroline (a zinc-specific chelator) and ethylenebis
      (oxyethylenenitrilo) tetraacetic acid (EGTA). Calcium reconstituted the activity
      of the EGTA-inhibited enzyme with an apparent dissociation constant (calcium) of
      1.2 mM. Developmental substrate gel analysis was performed using various stage
      embryos. The 55 and 32 kDa species comigrated with gelatin-cleavage activities
      present in sea urchin embryos. Collectively, the results reported here document a
      zymogen activation pathway which generates a 55 kDa, gelatin-cleaving activity
      within the extraembryonic HL. This species displayed characteristics of the
      matrix metalloproteinase class of ECM modifying enzymes.

PMID- 15449316
TI  - Gene positional changes relative to the nuclear substructure during carbon
      tetrachloride-induced hepatic fibrosis in rats.
AB  - In the interphase nucleus the DNA of higher eukaryotes is organized in loops
      anchored to a substructure known as the nuclear matrix (NM). The topological
      relationship between gene sequences located in the DNA loops and the NM appears
      to be very important for nuclear physiology because processes such as
      replication, transcription, and processing of primary transcripts occur at
      macromolecular complexes located at discrete sites upon the NM. Mammalian
      hepatocytes rarely divide but preserve a proliferating capacity that is displayed
      in vivo after specific stimulus. We have previously shown that transient changes
      in the relative position of specific genes to the NM occur during the process of
      liver regeneration after partial ablation of the liver, but also that such
      changes correlate with the replicating status of the cells. Moreover, since
      chronic exposure to carbon tetrachloride (CCl4) leads to bouts of hepatocyte
      damage and regeneration, and eventually to non-reversible liver fibrosis in the
      rat, we used this animal model in order to explore if genes that show
      differential activity in the liver change or modify their relative position to
      the NM during the process of liver fibrosis induction. We found that changes in
      the relative position of specific genes to the NM occur during the chronic
      administration of CCl4, but also that such changes correlate with the
      proliferating status of the hepatocytes that goes from quiescence to regeneration
      to replicative senescence along the course of CCl4-induced liver fibrosis,
      indicating that specific configurations in the higher-order DNA structure
      underlie the stages of progression towards liver fibrosis.

PMID- 15449317
TI  - P2Y receptors play a critical role in epithelial cell communication and
      migration.
AB  - Cellular injury induces a complex series of events that involves Ca2+ signaling,
      cell communication, and migration. One of the first responses following
      mechanical injury is the propagation of a Ca2+ wave (Klepeis et al. [2001] J Cell
      Sci 114(Pt 23):4185-4195). The wave is generated by the extracellular release of
      ATP, which also induces phosphorylation of ERK (Yang et al. [2004] J Cell Biochem
      91(5):938-950). ATP and other nucleotides, which bind to and activate specific
      purinergic receptors were used to mimic injury. Our goal was to determine which
      of the P2Y purinergic receptors are expressed and stimulated in corneal
      epithelial cells and which signaling pathways are activated leading to changes in
      cell migration, an event critical for wound closure. In this study, we
      demonstrated that the P2Y1, P2Y2, P2Y4, P2Y6, and P2Y11 receptors were present in
      corneal epithelial cells. A potency profile was determined by Ca2+ imaging for
      nucleotide agonists as follows: ATP > or = UTP > ADP > or = UDP. In contrast,
      negligible responses were seen for beta,gamma-meATP, a general P2X receptor
      agonist and adenosine, a P1 receptor agonist. Homologous desensitization of the
      Ca2+ response was observed for the four nucleotides. However, P2Y receptor
      internalization and degradation was not detected following stimulation with ATP,
      which is in contrast to EGFR internalization observed in response to EGF. ATP
      induced cell migration was comparable to that of EGF and was maximal at 1 microM.
      Cells exposed to ATP, UTP, ADP, and UDP demonstrated a rapid twofold increase in
      phosphorylation of paxillin at Y31 and Y118, however, there was no activation
      elicited by beta,gamma-meATP or adenosine. Additional studies demonstrated that
      wound closure was inhibited by reactive blue 2. These results indicate that P2Y
      receptors play a critical role in the injury repair process.

PMID- 15449318
TI  - Egr-1 is activated by 17beta-estradiol in MCF-7 cells by mitogen-activated
      protein kinase-dependent phosphorylation of ELK-1.
AB  - Early growth response-1 (Egr-1) is an immediate-early gene induced by E2 in the
      rodent uterus and breast cancer cells. E2 induces Egr-1 mRNA and protein levels
      in MCF-7 human breast cancer cells and reporter gene activity in cells
      transfected with pEgr-1A, a construct containing the -600 to +12 region of the
      Egr-1 promoter linked to the firefly luciferase gene. Deletion analysis of the
      Egr-1 promoter identified a minimal E2-responsive region of the promoter that
      contained serum response element (SRE)3 (-376 to -350) which bound Elk-1 and
      serum response factor (SRF) in gel mobility shift assays. Hormone-responsiveness
      of Egr-1 in MCF-7 cells was specifically inhibited by PD98059, a mitogen
      activated protein kinase kinase inhibitor, but not by LY294002, an inhibitor of
      phosphatidylinositol-3-kinase (PI3-K). These results contrasted with hormone
      dependent activation of the SRE in the c-fos promoter, which was inhibited by
      both PD98059 and LY294002. Differences in activation of the SREs in Egr-1 and c
      fos were related to promoter sequence, which defines the affinities of Elk-1 and
      SRF to their respective binding sites. Thus, Egr-1, like c-fos, is activated
      through non-genomic (extranuclear) pathways of estrogen action in breast cancer
      cells.

PMID- 15449319
TI  - A novel subfamily of zinc finger genes involved in embryonic development.
AB  - C2H2 zinc finger proteins make up one of the largest protein families in
      eukaryotic organisms. Recent study in several different systems has identified a
      set of novel zinc finger proteins that appear to form a distinct subfamily that
      we have named the NET family. Members of the NET family (Noc, Nlz, Elbow, and Tlp
      1) share two protein motifs--a buttonhead box and an Sp motif--with zinc finger
      proteins from the Sp family. However, the NET family is uniquely characterized by
      a single atypical C2H2 zinc finger, in contrast to the Sp family that contains
      three tandem C2H2 fingers. Here, we review current information about the
      biochemical function and in vivo role for members of this subfamily. In general,
      NET family proteins are required during embryonic development. They appear to act
      by regulating transcription, most likely as repressors, although they are
      unlikely to bind DNA directly. In the future, it will be important to directly
      test if NET family proteins control transcription of specific target genes,
      perhaps via interactions with DNA-binding transcription factors, as well as to
      further explore their function in vivo.

PMID- 15449320
TI  - Role of cell signalling involved in induction of apoptosis by benzo[a]pyrene and
      cyclopenta[c,d]pyrene in Hepa1c1c7 cells.
AB  - The reactive metabolites of benzo[a]pyrene (B[a]P) and cyclopenta[c,d]pyrene
      (CPP) induced an accumulation/phosphorylation of p53 in Hepa1c1c7 cells, whereas
      inhibition of p53 reduced the apoptosis. Judged by the inhibiting effect of
      wortmannin, phosphatidyl-inositol-3 (PI-3) kinases such as DNA-dependent protein
      kinase (DNA-PK), ATM (ataxia-telangiectasia mutated), and/or ATR (ATM related
      kinase), appeared to be involved in the DNA damage recognition and the B[a]P-/CPP
      induced accumulation of p53. B[a]P and CPP also induced phosphorylation of jun-N
      terminal kinase (JNK) and p38 mitogen activated protein kinase (MAPK). While
      inhibition of JNK had no effects on the B[a]P-/CPP-induced apoptosis, inhibition
      of p38 MAPK activity reduced this effect. Interestingly, survival signals such as
      phosphorylation of Akt and Bad seemed to be induced by the B[a]P-/CPP-compounds.
      Furthermore, also extracellular signal-regulated kinase (ERK)1/2 was activated
      and seemed to function as a survival signal in B[a]P-/CPP-induced apoptosis.

PMID- 15449321
TI  - A fragment of the hypophosphatemic factor, MEPE, requires inducible
      cyclooxygenase-2 to exert potent anabolic effects on normal human marrow
      osteoblast precursors.
AB  - MEPE, 56.6 kDa protein isolated from tumors associated with hypophosphatemic
      osteomalacia, increases renal phosphate excretion and is expressed in normal
      human bone cells. AC-100, a central 23-amino acid fragment of MEPE, contains
      motifs that are important in regulating cellular activities in the bone
      microenvironment. Thus, we assessed in vitro effects of AC-100 on multipotential
      normal human marrow stromal (hMS) cells that have the capacity to differentiate
      into mature osteoblasts. Proliferation was quantified by [H3]thymidine uptake and
      cell counting and differentiation by the levels of mRNA for the alpha2-chain of
      type I procollagen (COL1A2), alkaline phosphatase (AP), and osteocalcin (OC)
      measured using real time reverse transcriptase PCR (RT-PCR) and by the formation
      of mineralized nodules. AC-100 increased proliferation by 257 +/- 89% (P <
      0.005), increased gene expression of COL1A2 by 339 +/- 85% (P < 0.005), AP by
      1,437 +/- 40% (P < 0.001), and OC by 1,962 +/- 337% (P < 0.001). In addition, it
      increased mineralized nodule formation by 81 +/- 14% (P < 0.001) in a dose- and
      time-dependent fashion. In equimolar dosages, the parent compound, MEPE, had the
      full activity of the AC-100 fragment. AC-100 elicited a comparable response to
      both IGF-I and BMP-2 with respect to proliferation and differentiation of hMS
      cells. Using gene expression microarray analysis, we demonstrated that AC-100
      increased (by approximately 3-fold) the mRNA for cyclooxgenase-2 (COX-2), an
      inducible enzyme required for prostaglandin synthesis. Moreover, NS-398, a
      specific inhibitor of COX-2 action completely blocked AC-100-induced increases in
      proliferation and differentiation. Thus, AC-100 has potent anabolic activity on
      osteoblast precursor cells in vitro and these effects require the induction of
      COX-2.

PMID- 15449322
TI  - Tumor-host interactions.
AB  - A number of malignant tumors interact with the host to cause a syndrome of
      cachexia, characterized by extensive loss of adipose tissue and skeletal muscle
      mass, but with preservation of proteins in visceral tissues. Although anorexia is
      frequently present, the body composition changes in cancer cachexia cannot be
      explained by nutritional deprivation alone. Loss of skeletal muscle mass is a
      result of depression in protein synthesis and an increase in protein degradation.
      The main degradative pathway that has been found to have increased expression and
      activity in the skeletal muscle of cachectic patients is the ubiquitin-proteasome
      proteolytic pathway. Cachexia-inducing tumors produce catabolic factors such as
      proteolysis-inducing factor (PIF), a 24 kDa sulfated glycoprotein, which inhibit
      protein synthesis and stimulate degradation of intracellular proteins in skeletal
      muscle by inducing an increased expression of regulatory components of the
      ubiquitin-proteasome proteolytic pathway. While the oligosaccharide chains in PIF
      are required to initiate protein degradation the central polypeptide core may act
      as a growth and survival factor. Only cachexia-inducing tumors are capable of
      elaborating fully glycosylated PIF, and the selectivity of production possibly
      rests with the acquisition of the necessary glycosylating enzymes, rather than
      expressing the gene for the polypeptide core. Loss of adipose tissue is probably
      the result of an increase in catabolism rather than a defect in anabolism. A
      lipid mobilizing factor (LMF), identical with the plasma protein Zn-alpha2
      glycoprotein (ZAG) is found in the urine of cachectic cancer patients and is
      produced by tumors causing a decrease in carcass lipid. LMF causes triglyceride
      hydrolysis in adipose tissue through a cyclic AMP-mediated process by interaction
      with a beta3-adrenoreceptor. Thus, by producing circulating factors certain
      malignant tumors are able to interfere with host metabolism even without
      metastasis to that particular site.

PMID- 15449323
TI  - Cytoprotection by bcl-2 gene transfer against ischemic liver injuries together
      with repressed lipid peroxidation and increased ascorbic acid in livers and
      serum.
AB  - The maximum gene exhibition was shown to be achieved at 48 h after transfection
      with human bcl-2 (hbcl-2) genes built in an SV40 early promoter-based plasmid
      vector and HVJ-liposome for cultured rat hepatocytes. The similar procedure of
      hbcl-2 transfection was therefore conducted for livers in rats via the portal
      vein, and after 48 h followed by post-ischemic reperfusion (I/R) operation for
      some hepatic lobes. The I/R-induced hepatic injuries were in situ observed as
      both cell morphological degeneration and cellular DNA strand cleavages around
      capillary vessels of the ischemic liver lobes as detected by HE stain and TUNEL
      assay, and were biochemically observed as release of two hepatic marker enzymes
      AST and ALT into serum. All the I/R-induced injuries examined were appreciably
      repressed for rats transfected with hbcl-2; hbcl-2 was expressed in hepatocytes
      around the capillaries of ischemic regions such as the median lobe and the left
      lobe, but scarcely around those of non-ischemic regions. Thus cytoprotection
      against I/R-induced injuries may be attributed to the I/R-promoted expression of
      transferred hbcl-2 genes. The possibility was examined firstly by
      methylphenylindole method, which showed that I/R-enhanced lipid peroxidation in
      the reference vector-transfected livers were markedly repressed in the hbcl-2
      transfected livers. Contents of ascorbic acid (Asc) in serum and livers of hbcl-2
      transfected rats were enriched, unexpectedly, versus those of non-transfected
      rats, and were as abundant as 1.90-fold and 1.95- to 2.60-fold versus those in
      the pre-ischemic state, respectively. After I/R, an immediate decline in serum
      Asc occurred in hbcl-2-transfectants, and was followed by prompt restoration up
      to the pre-ischemic Asc levels in contrast to the unaltered lower Asc levels in
      non-transfectants except a transient delayed increase. Hepatic Asc contents were
      also diminished appreciably at the initial stage after I/R in the ischemic lobes
      of hbcl-2-transfectants, which however retained more abundant Asc versus non
      transfectants especially at the initial I/R stage when scavenging of the
      oxidative stress should be most necessary for cytoprotection. The results showed
      a close correlation between cytoprotection by exogenously transferred hbcl-2 and
      repressive effects on the lipid peroxidation associated with Asc consumption or
      redistribution.

PMID- 15449324
TI  - Diagnostic value of periodic complexes in Creutzfeldt-Jakob disease.
AB  - In 1996, our group published objective electroencephalogram (EEG) criteria to
      define periodic sharp-wave complexes (PSWCs) suggestive for Creutzfeldt-Jakob
      disease (CJD). These criteria have since then been strictly applied in all cases
      reported to us as possible CJD in the course of the German CJD surveillance
      study. Furthermore, EEG analysis of the records was performed without any
      additional information on complementary clinical and laboratory data. In this
      study, we investigated sensitivity, specificity, and the predictive values of
      these EEG criteria exclusively in cases in which autopsy confirmed (n=150) or
      excluded (n=56) CJD. EEG criteria were positive in 64% (n=96) of the CJD cases
      and falsely positive in 9% (n=5) of other dementias. The resulting figures for
      sensitivity, specificity, and positive and negative predictive values were 64%,
      91%, 95%, and 49%, respectively. In the falsely positive cases, Alzheimer's
      disease (n=4) and vascular dementia (n=1) were the underlying diseases. However,
      only in one of these five cases both clinical and EEG data would have led to the
      false-positive result to diagnose probable CJD. These data prove the high
      diagnostic value of our objective EEG criteria in CJD.

PMID- 15449325
TI  - Metabolic changes in vestibular and visual cortices in acute vestibular neuritis.
AB  - Five right-handed patients with a right-sided vestibular neuritis were examined
      twice with fluorodeoxyglucose positron emission tomography while lying supine
      with eyes closed: once during the acute stage (mean, 6.6 days) and then 3 months
      later when central vestibular compensation had occurred. Regional cerebral
      glucose metabolism (rCGM) was significantly increased (p <0.001 uncorrected)
      during the acute stage in multisensory vestibular cortical and subcortical areas
      (parietoinsular vestibular cortex in the posterior insula, posterolateral
      thalamus, anterior cingulate gyrus [Brodmann area 32/24], pontomesencephalic
      brainstem, hippocampus). Simultaneously, there was a significant rCGM decrease in
      the visual (Brodmann area 17 to 19) and somatosensory cortex areas in the
      postcentral gyrus as well as in parts of the auditory cortex (transverse temporal
      gyrus). Fluorodeoxyglucose positron emission tomography thus allows imaging of
      the cortical activation pattern that is induced by unilateral peripheral
      vestibular loss. It was possible to demonstrate that the central vestibular
      system including the vestibular cortex exhibits a visual-vestibular activation
      deactivation pattern during the acute stage of vestibular neuritis similar to
      that in healthy volunteers during unilateral labyrinthine stimulation. Contrary
      to experimental vestibular stimulation, the activation of the vestibular cortex
      was not bilateral but was unilateral and contralateral to the right-sided
      labyrinthine failure.

PMID- 15449326
TI  - Anatomy of and patterns of water currents through the mantle cavities of
      pleurotomariid gastropods.
AB  - The paired pallial organs of pleurotomariids (slit shells) are generally
      interpreted as representing the primitive gastropod condition. Relatively few
      individual pleurotomariids have been observed alive; most anatomical descriptions
      have been based on retracted, preserved material. In this study, live animals
      were observed in still and moving water, videotaped, photographed, and relaxed
      prior to anatomical description. The pleurotomariid Perotrochus maureri formed a
      siphon with its mantle at the posterior end of the slit in the shell. As
      expected, water was expelled from the mantle cavity through this siphon. Dye
      released along the aperture, the area traditionally considered to be the
      incurrent window, was never observed to enter the mantle cavity. Instead, water
      entered through the slit just anterior to the siphon. A similar pattern was
      observed in the deep-slit pleurotomariid Entemnotrochus adansonianus. Thus the
      "anal" slit provided the sites for the incurrent as well as the excurrent
      windows. This surprising flow pattern is inconsistent with the traditional
      scenario of early gastropod evolution.

PMID- 15449327
TI  - Histopathologic changes induced by the microtubule-stabilizing agent Taxol in the
      rat hippocampus in vivo.
AB  - Microtubules and their associated proteins play a prominent role in neuronal
      morphology, axonal transport, neuronal plasticity, and neuronal degeneration. It
      has been proposed that microtubule damage is sufficient to induce neuronal death.
      In this regard, the microtubule-stabilizing agent Taxol could be a useful tool to
      reproduce some aspects of neurodegenerative diseases associated with disturbances
      of the cytoskeleton and alterations in axonal transport. Although differential
      effects of Taxol on neuronal viability have been found in vitro, Taxol toxicity
      in the central nervous system remains to be addressed. We studied the effects of
      Taxol on neuronal morphology and viability as well as changes in microtubule
      associated proteins MAP2 and tau in rat hippocampus. Our results show that Taxol
      induces dose-dependent neuronal death accompanied by the loss of MAP2 and the
      presence of dystrophic neurites. Interestingly paired helical filament (PHF)-1
      immunoreactivity, which is associated with a phosphorylated epitope of tau
      proteins, was induced in the damaged hippocampus. Our results suggest that
      microtubule dynamics have a role in maintenance of neuronal morphology and
      survival in vivo, and that modifications in microtubule dynamics, may alter the
      content and neuronal distribution of MAP2 and promote alterations in the
      phosphorylation state of tau.

PMID- 15449328
TI  - Dependency issues in survival analyses of 55,782 primary hip replacements from
      47,355 patients.
AB  - Artificial hip joints are used in only one hip for about 85 per cent of the
      patients and in both hips (bilateral) for about 15 per cent of the patients. The
      occurrence of bilateral prostheses and the influence they have in survival
      analyses of joint arthroplasties are seldom considered. In this study we
      therefore focus on issues related to bilateral primary hip prostheses, time to
      revision surgery, and some commonly used statistical methods. We used information
      from 47,355 patients with 55,782 primary hip prostheses reported to the Norwegian
      Arthroplasty Register between 1987 and 2000. Due to the large number of
      diagnoses, fixation techniques for the prostheses, and combination of prostheses
      brands, we furthermore considered a 'homogeneous' subset of 8703 prostheses from
      7930 patients with primary osteoarthritis, and Charnley prosthesis fixed with
      antibiotic-containing Palacos cement. Kaplan-Meier curves for all prostheses,
      ignoring that some patients have bilateral prostheses, were compared with Kaplan
      Meier curves using only the first inserted prostheses, and with survival curves
      modified for patients with bilateral prostheses. Cox regression analyses were
      used to assess explanatory variables and to adjust for confounding factors. The
      results from the ordinary Cox regression analyses were compared with results from
      a marginal model, a shared gamma frailty model, and a model using a time
      dependent covariate to condition on failures in the opposite hip. We found no
      practical difference between the three calculated survival curves for the hip
      replacement data. The ordinary Cox-model and the marginal model gave equivalent
      results. In the shared gamma frailty model estimates for the risk factors were
      comparable with the former two approaches. The estimated frailty variance was
      higher when all data were used, even after adjustment for confounding factors.
      For the 'homogeneous' data the estimated frailty variance was negligible. Using a
      time dependent covariate to condition on previous revisions in the opposite hip,
      we found a higher risk of revision for the remaining primary hip prosthesis if
      the opposite hip had been revised (RR = 3.49, p < 0.0001). There was no
      difference in risk for revision between right and left hip prostheses. If the
      time interval between the two primary operations was more than two years, for the
      full data, the first hip prosthesis had an increased risk of revision compared to
      prostheses in patients with only one prosthesis (RR = 1.25, p = 0.01). For the
      'homogeneous' data no statistically significant difference was found between
      unilateral and bilateral prostheses. A revision in one hip, for patients with
      bilateral prostheses, is a risk factor for revision of the other hip. Thus, in
      analyses of prostheses survival, dependencies between two hip prostheses from one
      patient should be considered. However, ignoring possible dependencies does not
      necessarily have an impact on the results on standard risk factors.

PMID- 15449329
TI  - A parametric survival model with an interval-censored covariate.
AB  - We present a parametric survival model whose particularity consists in the
      inclusion of an interval-censored covariate. The methodology is motivated by a
      study on injecting drug users in Badalona (Spain), most of whom suffered HIV
      infection as a result of their drug addiction. The study aims to examine the
      possible association between the elapsed time from first injecting drug use until
      HIV infection and the subsequent AIDS incubation period. Whereas the moment of
      HIV infection cannot be observed exactly and is therefore interval-censored, time
      until AIDS onset is doubly-censored. For the maximization of the resulting
      likelihood function, we use a numerical solver. Maximization is carried out by
      means of the mathematical programming language AMPL.

PMID- 15449330
TI  - Last observation carry-forward and last observation analysis.

PMID- 15449332
TI  - Analysis of data with multiple sources of correlation in the framework of
      generalized estimating equations.
AB  - This paper is motivated by a study of physical activity participation habits in
      African American women with three potential sources of correlation among study
      outcomes, according to method of assessment, timing of measurement, and intensity
      of physical activity. To adjust for the multiple sources of correlation in this
      study, we implement an approach based on generalized estimating equations that
      models association via a patterned correlation matrix. We present a general
      algorithm that is relatively straightforward to program, an analysis of our
      physical activity study, and some asymptotic relative efficiency comparisons
      between correctly specifying the correlation structure vs ignoring two sources of
      correlation in the analysis of data from this study. The efficiency comparisons
      demonstrate that correctly modeling the correlation structure can prevent
      substantial losses in efficiency in estimation of the regression parameter.

PMID- 15449333
TI  - Joint modelling of multivariate longitudinal profiles: pitfalls of the random
      effects approach.
AB  - Due to its flexibility, the random-effects approach for the joint modelling of
      multivariate longitudinal profiles received a lot of attention in recent
      publications. In this approach different mixed models are joined by specifying a
      common distribution for their random-effects. Parameter estimates of this common
      distribution can then be used to evaluate the relation between the different
      responses. Using bivariate longitudinal measurements on pure-tone hearing
      thresholds, it will be shown that such a random-effects approach can yield
      misleading results for evaluating this relationship.

PMID- 15449334
TI  - Including a time-of-year effect in the analysis of a matched case-control study.
AB  - Motivated by a matched case-control study to investigate potential risk factors
      for meningococcal disease amongst adolescents, we consider the analysis of
      matched case-control studies where disease incidence, and possibly other risk
      factors, vary with time of year. For the cases, the time of infection may be
      recorded. For controls, however, the recorded time is simply the time of data
      collection, which is shortly after the time of infection for the matched case,
      and so depends on the latter. We show that the effect of risk factors and
      interactions may be adjusted for the time of year effect in a standard
      conditional logistic regression analysis without introducing any bias. We also
      show that, if the time delay between data collection for cases and controls is
      constant, provided this delay is not very short, estimates of the time of year
      effect are approximately unbiased. In the case that the length of the delay
      varies over time, the estimate of the time of year effect is biased. We obtain an
      approximate expression for the degree of bias in this case.

PMID- 15449335
TI  - Designing follow-up intervals.
AB  - When an examination is needed to determine if an event has occurred there will be
      a loss of efficiency in using the resulting interval-censored data instead of the
      exact event times. In designing follow-up intervals this loss for longer
      intervals needs to be weighed against extra visits required by shorter intervals.
      We obtain results to quantify this for the estimation of the median and mean
      survival and for covariates in parametric regression models with equally spaced
      examination times. Asymptotic information loss for the log-normal and Weibull
      distributions are similar when comparisons are made between corresponding members
      of the two families. For distributions with coefficients of variation of 50 per
      cent or more, a choice of interval from 0.25 to 0.7 times the median is
      recommended.

PMID- 15449336
TI  - Controlling for provider of treatment in the modelling of respiratory disease
      risk near cokeworks.
AB  - The improved quality of hospital admissions data makes them a valuable resource
      for researchers. However, we show that, when multiple providers of health care
      are considered, the provider (in this case hospital) may act like other
      confounders such as socio-economic status, and hence must be controlled for. Such
      control is not as straightforward as for conventional confounders, however, but
      we describe a method that is appropriate under certain assumptions. We also
      describe a number of other statistical issues, such as the modelling of spatial
      and non-spatial overdispersion, that arose during the use of hospital data in a
      study to investigate the possible adverse health effects of living in proximity
      to six cokeworks groups in England and Wales. The outcome data that we consider
      consist of hospital admissions for all respiratory disease in the under-5s. The
      ecological level of the analysis is the census-defined enumeration district, and
      the main (proxy) exposure measure utilised is the spatial location of the
      enumeration district population-weighted centroid in relation to the cokeworks.
      We focus on the Teesside cokeworks group, for which we also had sulphur dioxide
      measurements from dispersion modelling as an alternative exposure measure. The
      major local providers varied appreciably in their standardized admission ratios
      for respiratory disease, and when provider was controlled for, the size of the
      observed excess risk found close to the cokeworks was decreased, making control
      for the provider of health care vital. However, the presence of multiple
      pollution sources, in addition to the usual shortcomings of ecological studies,
      makes interpretation difficult.

PMID- 15449337
TI  - Parametric accelerated failure time models with random effects and an application
      to kidney transplant survival.
AB  - Accelerated failure time models with a shared random component are described, and
      are used to evaluate the effect of explanatory factors and different transplant
      centres on survival times following kidney transplantation. Different
      combinations of the distribution of the random effects and baseline hazard
      function are considered and the fit of such models to the transplant data is
      critically assessed. A mixture model that combines short- and long-term
      components of a hazard function is then developed, which provides a more flexible
      model for the hazard function. The model can incorporate different explanatory
      variables and random effects in each component. The model is straightforward to
      fit using standard statistical software, and is shown to be a good fit to the
      transplant data.

PMID- 15449338
TI  - Combination of direct and indirect evidence in mixed treatment comparisons.
AB  - Mixed treatment comparison (MTC) meta-analysis is a generalization of standard
      pairwise meta-analysis for A vs B trials, to data structures that include, for
      example, A vs B, B vs C, and A vs C trials. There are two roles for MTC: one is
      to strengthen inference concerning the relative efficacy of two treatments, by
      including both 'direct' and 'indirect' comparisons. The other is to facilitate
      simultaneous inference regarding all treatments, in order for example to select
      the best treatment. In this paper, we present a range of Bayesian hierarchical
      models using the Markov chain Monte Carlo software WinBUGS. These are
      multivariate random effects models that allow for variation in true treatment
      effects across trials. We consider models where the between-trials variance is
      homogeneous across treatment comparisons as well as heterogeneous variance
      models. We also compare models with fixed (unconstrained) baseline study effects
      with models with random baselines drawn from a common distribution. These models
      are applied to an illustrative data set and posterior parameter distributions are
      compared. We discuss model critique and model selection, illustrating the role of
      Bayesian deviance analysis, and node-based model criticism. The assumptions
      underlying the MTC models and their parameterization are also discussed.

PMID- 15449339
TI  - Multidimensional proteomic analysis of photosynthetic membrane proteins by liquid
      extraction-ultracentrifugation-liquid chromatography-mass spectrometry.
AB  - The membrane protein components of photosystem I (PSI) and II (PSII) from
      different species were prefractionated by liquid extraction and sucrose gradient
      ultracentrifugation and subsequently analyzed by reversed-phase high-performance
      liquid chromatography-electrospray ionization-mass spectrometry (RP-HPLC-ESI-MS)
      using poly-(styrene-divinylbenzene)-based monolithic capillary columns. The
      analytical method was shown to be very flexible and enabled the identification of
      antenna proteins as well as most of the proteins of the reaction center from PSI
      and PSII in various plant species with few RP-HPLC-ESI-MS analyses necessitating
      only minor adaptations in the gradients of acetonitrile in 0.05% aqueous
      trifluoroacetic acid. The membrane proteins, ranging in molecular mass (Mr) from
      4196 (I protein) to more than 80,000 (PSI A/B) as well as isoforms were
      identified on the basis of their intact Mr and comparison with Mr deduced from
      known DNA or protein sequences. High quality mass spectra enabled the
      identification and quantitation of the nonphosphorylated and phosphorylated
      reaction center subunits D1, D2, and CP43 of PSII, containing five to seven
      membrane-spanning alpha-helices. Because of its high flexibility and suitability
      for proteins having a very wide range of Mr and hydrophobicities, the method is
      generally applicable to the analysis of complex mixtures of membrane proteins.

PMID- 15449340
TI  - Application of RNA interference to chicken embryos using small interfering RNA.
AB  - Gene silencing using small interfering RNA (siRNA) is not established in avian
      species. The present study was performed to evaluate RNA interference (RNAi) in
      the chicken embryo by using a dual fluorescence reporter assay, a plasmid
      encoding green fluorescent protein (GFP) and a plasmid encoding red fluorescent
      protein (RFP). The siRNA targeting the GFP mRNA sequence (GFP-siRNA) with both
      plasmids was introduced into cultured cells and whole embryos by lipofection and
      microelectroporation, respectively. GFP- and RFP-expressed cells and embryos were
      observed under fluorescent microscopy and analyzed by flow cytometer, and their
      mRNAs were analyzed by reverse transcription-PCR (RT-PCR). The strong
      fluorescence was observed by introducing both plasmids into cells. The intensity
      of the green fluorescence generated by GFP was greatly suppressed by introducing
      GFP-siRNA. RT-PCR analysis showed that introducing GFP-siRNA also decreased GFP
      mRNA levels. In contrast to GFP, the intensity of the red fluorescence generated
      by RFP and the RFP mRNA levels remained unchanged. In whole embryos, also,
      introducing GFP-siRNA specifically suppressed GFP expression, and the suppression
      was maintained for at least 72 h. Consequently, it was concluded that the gene
      silencing using siRNA is applicable to analyzing the function of genes of
      interest during avian embryogenesis.

PMID- 15449341
TI  - Hypergravity decreases carbonic anhydrase-reactivity in inner ear maculae of
      fish.
AB  - Previous investigations revealed that fish inner ear otolith growth depends on
      the amplitude and the direction of gravity. Both otolith total size, otolith
      bilateral size-asymmetry and the total and bilateral calcium-incorporation are
      also affected by gravity. Hypergravity, e.g., slows down otolith growth and
      diminishes bilateral otolith asymmetry as compared to 1 g control specimens
      raised in parallel. Since the enzyme carbonic anhydrase (CA) plays a prominent
      role in otolithic calcification, the reactivity of inner ear CA during otolith
      growth under hypergravity was investigated. CA-reactivity was demonstrated
      histochemically and densitometrically on sections of inner ear maculae of larval
      cichlid fish (Oreochromis mossambicus), that were kept for 6 hrs in a 3 g
      hypergravity centrifuge. The total unilateral macular CA-reactivity and the
      bilateral difference in CA between the left and the right maculae were
      significantly lower in 3 g animals than in 1g controls. The result is in complete
      agreement with previous studies indicating that a regulatory mechanism, which
      adjusts otolith size and asymmetry towards the gravity vector, acts via
      activation/deactivation of macular CA.

PMID- 15449342
TI  - Effects of post-treatment with 6-dimethylaminopurine (6-DMAP) on ethanol
      activation of mouse oocytes at different ages.
AB  - To study the effect of post-treatment with 6-Dimethylaminopurine (6-DMAP) on
      oocyte activation and development, mouse oocytes collected at different times
      post human chorion gonadotropin (hCG) injection were incubated in 6-DMAP
      containing Chatot-Ziomek-Bavister (CZB) medium for different periods after
      ethanol exposure, and activation and development were observed. When oocytes were
      cultured in 6-DMAP without prior ethanol exposure, the highest activation rate
      was only 40%. Incubation in 6-DMAP for 6 h following ethanol exposure
      significantly (P < 0.05) increased the activation rate in oocytes recovered 15
      and 18 h post hCG, but this effect was not significant in the 21 h oocytes. When
      oocytes were incubated in 6-DMAP for 1 h at different time points after ethanol,
      a 6-DMAP susceptible temporal window was found to be located from the second to
      the fifth h in the 18 h oocytes and from the fourth to the fifth h in the 15 h
      oocytes, and within the window, the duration of 6-DMAP incubation can be reduced
      to 0.5 h with more than 80% activation. With the 13 h oocytes, however, 6-DMAP
      incubation can only be shortened to 3 h and no specific temporal window was
      identified. Oocytes that were incubated in 6-DMAP for 1 or 2 h after ethanol
      exposure developed to morula/blastocyst stages at significantly (P < 0.05) higher
      rates than those incubated in 6-DMAP for 6 h. Our results suggested that (i) long
      duration of 6-DMAP incubation impaired the development of mouse parthenogenotes;
      (ii) the effect of 6-DMAP alone was limited without prior ethanol exposure; (iii)
      the egg age affected both the timing of 6-DMAP susceptibility and the duration of
      exposure required to obtain a maximal activating effect; (iv) the most effective
      activating protocols varied for oocytes of different ages.

PMID- 15449343
TI  - Molecular characterization of a cDNA encoding vitellogenin in the coonstriped
      shrimp, Pandalus hypsinotus and site of vitellogenin mRNA expression.
AB  - In order to determine the primary structure of vitellogenin in a protandric
      species, the coonstriped shrimp Pandalus hypsinotus, we previously purified four
      vitellin components (designated as VnA, VnB, VnC, and VnD, respectively), and
      chemically analyzed their partial amino acid sequences. In this study, we
      subsequently cloned a cDNA encoding vitellogenin in this species based on the N
      terminal and internal amino acid sequences of VnA, as well as the N-terminal
      sequence of VnC. The open reading frame of this cDNA encoded a pro-vitellogenin
      in which vitellins were arranged as follows: NH2-VnA-VnB-VnC/D-COOH. The deduced
      amino acid sequence possessed a single consensus cleavage sequence, R-X-K/R-R,
      along the lines of vitellogenins reported in other crustaceans and insects, and
      the N-terminal sequence of VnB was immediately preceded by this sequence. The
      comparison of primary structures revealed the existence of a basic and
      characteristic structure for the vitellogenin molecule in decapod crustacean
      species, and phylogenetic analysis reflected the current taxonomic
      classifications of Crustacea. An approximately 8 kb-long transcript of the
      vitellogenin gene was detected in the hepatopancreas of female shrimps having a
      gonadosomatic index higher than 1.0 by Northern blot analysis, but was not
      observed in the hepatopancreas and gonads of male shrimps and the hepatopancreas
      of female shrimps having a gonadosomatic index lower than 1.0. These results
      indicate that the hepatopancreas is responsible for vitellogenin synthesis.

PMID- 15449344
TI  - L.S. stone: lens regeneration--contributions to the establishment of an in vivo
      model of transdifferentiation.

PMID- 15449345
TI  - Perception and possible utilization of moonlight intensity for reproductive
      activities in a lunar-synchronized spawner, the golden rabbitfish.
AB  - Rabbitfishes are known to spawn synchronously around the species-specific lunar
      phase. It is considered that they perceive and utilize cues from the moon in
      order to be synchronized gonadal development and spawning with the lunar cycle.
      Using the golden rabbitfish, Siganus guttatus, which spawns synchronously around
      the first quarter moon during the reproductive season, we measured the
      fluctuation of melatonin levels and examined the response of the fish to
      moonlight intensity. Daily fluctuation of melatonin concentration in the blood of
      golden rabbitfish showed low levels during daytime and high levels during night
      time, suggesting that melatonin functions in the perception and utilization of
      photoperiod. Plasma melatonin concentration at the new moon was higher than that
      at the full moon. When the fish were exposed to moonlight at midnight of the both
      moon phases, the melatonin concentrations decreased to the control levels. These
      results show that the fish possibly perceive moonlight intensity and plasma
      melatonin fluctuates according to 'lightness' at a point of night. At the first
      spawning period (experiment was started one month before the spawning), the fish
      reared under natural conditions spawned at the expected spawning dates, whereas
      the fish reared under the constant darkness and lightness of night did not spawn.
      At the second spawning period (experiment was started 2 weeks before the
      spawning), the fish reared under the conditions of natural and constant darkness
      of night spawned but not that of constant lightness of night. It is possible that
      night conditions are related to synchronous gonadal development and spawning in
      the golden rabbitfish.

PMID- 15449346
TI  - Cross communication between signaling pathways: juvenoid hormones modulate
      ecdysteroid activity in a crustacean.
AB  - Methyl farnesoate is a juvenoid hormone that regulates a variety of processes in
      crustaceans including male sex determination among daphnids (Branchiopoda,
      Cladocera). The synthetic juvenoids pyriproxyfen and fenoxycarb mimic the action
      of methyl farnesoate in daphnids. In the present study we tested the hypothesis
      that juvenoids also can regulate ecdysteroid activity in a crustacean (Daphnia
      magna). Methyl farnesoate, pyriproxyfen, and fenoxycarb all disrupted ecdysteroid
      regulated aspects of embryo development in daphnids. Exposure of ecdysteroid
      responsive cells to 20-hydroxyecdysone reduced cell proliferation and increased
      mRNA levels of the ecdysone receptor and its partner protein ultraspiracle. Co
      treatment of cells with the juvenoid pyriproxyfen attenuated all of these
      ecdysteroid mediated responses. While juvenoids functioned as anti-ecdysteroids
      in both intact embryos and in cultured cells, 20-hydroxyecdysone showed no
      evidence of acting as an anti-juvenoid. The combined effects of pyroproxyfen with
      the ecdysteroid synthesis inhibitor fenarimol and the ecdysteroid receptor
      antagonist testosterone were evaluated in an effort to discern whether the action
      of the juvenoids were additive with those of know anti-ecdysteroids. The anti
      ecdysteroid effects of pyriproxyfen were non-additive with those of either anti
      ecdysteroid. Rather, joint effects conformed to a model of synergy. These results
      demonstrated that juvenoids elicit anti-ecdysteroidal activity in a crustacean
      through a unique mechanism of action. A model involving receptor partner
      deprivation is proposed that explains the synergistic interactions observed.

PMID- 15449347
TI  - Osmoregulatory action of 17beta-estradiol in the gilthead sea bream Sparus
      auratus.
AB  - The osmoregulatory action of 17beta-estradiol (E2) was examined in the euryhaline
      teleost Sparus auratas. In a first set of experiments, fish were injected once
      with vegetable oil containing E2 (1, 2 and 5 microg/g body weight), transferred
      12h after injection from sea water (SW, 38 ppt salinity) to hypersaline water
      (HSW, 55 ppt) or to brackish water (BW, 5 ppt salinity) and sampled 12h later
      (i.e. 24 h post-injection). In a second experiment, fish were injected
      intraperitoneally with coconut oil alone or containing E2 (10 microg/g body
      weight) and sampled after 5 days. In the same experiment, after 5 days of
      treatment, fish of each group were transferred to HSW, BW and SW and sampled 4
      days later (9 days post-implant). Gill Na+,K+ -ATPase activity, plasma E2 levels,
      plasma osmolality, and plasma levels of ions (sodium and calcium), glucose,
      lactate, protein, triglyceride, and hepatosomatic index were examined. Transfer
      from SW to HSW produced no significant effects on any parameters assessed. E2
      treatment did not affect any parameter. Transfer from SW to BW resulted in a
      significant decrease in plasma osmolality and plasma sodium but did not affect
      gill Na+,K+ -ATPase activity. A single dose of E2 attenuated the decrease in
      these parameters after transfer from SW to BW, but was without effect on gill
      Na+,K+ -ATPase activity. An implant of E2 (10 microg/g body weight) for 5 days
      significantly increased plasma calcium, hepatosomatic index, plasma metabolic
      parameters, and gill Na+,K+ -ATPase activity. In coconut oil-implanted (sham)
      fish, transfer from SW to HSW or BW during 4 days significantly elevated gill
      Na+,K+ -ATPase. Gill Na+,K+ -ATPase activity remained unaltered after transfer of
      E2-treated fish to HSW or BW. However, in E2-treated fish transferred from SW to
      SW (9 days in SW after E2-implant), gill Na+,K+ -ATPase activity decreased with
      respect to HSW- or BW-transferred fish. Shams transferred to HSW showed increased
      levels of lactate, protein, and trygliceride in plasma, while those transferred
      to BW only displayed increased trygliceride levels. E2-treated fish transferred
      to HSW showed higher protein levels without any change in other plasmatic
      parameters, while those transferred to BW displayed elevated plasma glucose
      levels but decreased osmolality and protein levels. These results substantiate a
      chronic stimulatory action of E2 on gill Na+,K+ -ATPase activity in the
      euryhaline teleost Sparus auratas.

PMID- 15449348
TI  - The quenching of electrochemiluminescence upon oligonucleotide hybridization.
AB  - Many genomic assays rely on a distance-dependent interaction between luminescent
      labels, such as luminescence quenching or resonance energy transfer. We studied
      the interaction between electrochemically excited Ru(bpy)(3) (2+) and Cy5 in a
      hybridization assay on a chip. The 3' end of an oligonucleotide was labelled with
      Ru(bpy)(3) (2+) and the 5' end of a complementary strand with Cy5. Upon the
      hybridization, the electrochemiluminescence (ECL) of Ru(bpy)(3) (2+) was
      efficiently quenched by Cy5 with a sensitivity down to 30 nmol/L of the Cy5
      labelled complementary strand. The quenching efficiency is calculated to be 78%.
      A similar phenomenon was observed in a comparative study using laser-excitation
      of Ru(bpy)(3) (2+). The hybridization with the non-labelled complementary or
      labelled non-complementary strand did not change the intensity of the ECL signal.
      Resonance energy transfer, electron transfer and static quenching mechanisms are
      discussed. Our results suggest that static quenching and/or electron transfer are
      the most likely quenching mechanisms.

PMID- 15449349
TI  - Interaction of metals with peroxidase--mediated luminol-enhanced,
      chemiluminescence (PLmCL).
AB  - The peroxidase-mediated luminol-enhanced chemiluminescence (PLmCL) method has
      been used to study the in vitro effect of contaminants such as heavy metals on
      the reactive oxygen species production by immunocytes. We were interested to know
      whether metals could directly affect peroxidase-mediated luminescence, taking
      horseradish peroxidase (HRP) as a model enzyme, since this could contribute to
      the inhibition of immunocyte LmCL. Copper inhibited PLmCL in a dose-dependent
      manner, while cadmium, iron, silver and lead only partly decreased the signal in
      the concentration range tested. In contrast, zinc enhanced the signal at high
      concentrations. Eventually, chromium, mercury and aluminium did not affect PLmCL.
      It is suggested that these effects reflect the ability of the metals to interact
      with the active site of the peroxidase. These results demonstrate that such
      interactions have to be considered when interpreting the effects of metals on
      immunocytes using the LmCL method.

PMID- 15449350
TI  - The forensic use of luminol chemiluminescence to detect traces of blood inside
      motor vehicles.
AB  - The luminol test for blood was carried out on a set of interior fittings and
      surfaces inside three different makes of modern motor car. The surfaces and
      fittings provided little interference with the test for blood, although there was
      some detectable chemiluminescence when the test was applied to blood-free
      material from a seatbelt, a boot-lining and a gear-knob. The case with which
      haemoglobin samples could be washed off interior car surfaces was also examined
      for seat fabrics, carpets, roof-linings and various other plastic interior
      surfaces. A standard wash with water alone was not very effective and removed
      only ca. 50% of the haemoglobin. A standard wash with soapy water or with a
      proprietary multipurpose car cleaner removed ca. 90% of the haemoglobin from the
      tested surface. The effect of high car interior temperatures on haemoglobin
      samples that were subsequently used in the luminol test was also examined. It was
      shown that the sensitivity of the luminol test was not decreased but was
      increased by the prior heating of a haemoglobin sample. This effect was
      attributed to the thermal conversion of haemoglobin to the more brighter catalyst
      for chemiluminescence, methaemoglobin. The enthalpy of this conversion in the
      solid state was found to be 14.1 kJ/mol.

PMID- 15449352
TI  - Current literature in mass spectrometry.

PMID- 15449351
TI  - Luminescence literature. Green fluorescent protein (GFP)--2001 literature.

PMID- 15449353
TI  - Functional neuroanatomy of perceiving surprised faces.
AB  - Surprise is one of six emotions having a specific and universally recognized
      facial expression. Functional imaging and neuropsychologic studies have uncovered
      partly separable neural substrates for perceiving different facial expressions;
      however, the functional neuroanatomy of perceiving surprised faces has not yet
      been investigated. Using functional magnetic resonance imaging (fMRI), we aimed
      to identify the neural substrate of surprise perception from facial expressions.
      Based on the assumption of unexpectedness and novelty as elicitors of facial
      surprise reactions, we hypothesized recruitment of medial temporal lobe
      structures implicated in novelty detection during the perception of surprise in
      others. Healthy subjects were scanned while they were presented with surprised
      faces. As a control, they viewed faces depicting neutral or disgust expressions.
      Activations during the emotional conditions were contrasted with each other and
      with the neutral face condition. Compared to both control conditions, perception
      of surprised facial expressions yielded consistently increased signals in the
      parahippocampal region, an area associated previously with novelty detection. Our
      findings therefore suggest a close relation between perceiving surprise in others
      and the response to novel events. Additionally, we confirmed activation of the
      insula during perception of disgust expressions.

PMID- 15449354
TI  - Musical training-induced functional reorganization of the adult brain: functional
      magnetic resonance imaging and transcranial magnetic stimulation study on amateur
      string players.
AB  - We used the combined technique of functional magnetic resonance imaging (fMRI)
      and transcranial magnetic stimulation (TMS) to observe changes that occur in
      adult brains after the practice of stringed musical instruments. We carried out
      fMRI on eight volunteers (aged 20-22 years): five novices and three individuals
      who had discontinued practice for more than 5 years. The motor paradigm contained
      a repetitive lift-abduction/fall-adduction movement of the left/right little
      finger, carried out with maximum efforts without pacing. The sensory paradigm was
      to stimulate the same little finger using a string. In parallel to the fMRI
      acquisition, TMS motor maps for the little finger were obtained using a frameless
      stereotactic neuronavigation system. After the baseline study, each participant
      began to learn a stringed instrument. Newly developed fMRI activations for the
      left little finger were observed 6 months after practice at multiple brain
      regions including inferior parietal lobule, premotor area (PMA), left precuneus,
      right anterior superior temporal gyrus, and posterior middle temporal gyrus. In
      contrast, new activations were rarely observed for the right little finger. The
      TMS study revealed new motor representation sites for the left little finger in
      the PMA or supplementary motor area (SMA). Unexpectedly, TMS motor maps for the
      right little finger were reduced significantly. Among new fMRI activations for
      sensory stimuli of the left little finger, the cluster of highest activation was
      located in the SMA. Collectively, these data provide insight into orchestrated
      reorganization of the sensorimotor and temporal association cortices contributing
      to the skillful fingering and musical processing after the practice of playing
      stringed instruments.

PMID- 15449355
TI  - Brain activity underlying emotional valence and arousal: a response-related fMRI
      study.
AB  - Emotional behavior is organized along two psychophysiologic dimensions: (1)
      valence, varying from negative to positive, and (2) arousal, varying from low to
      high. Behavioral responses along these dimensions are assumed to be mediated by
      different brain circuits. We recorded startle reflex modulation and skin
      conductance responses in healthy volunteers during functional magnetic resonance
      imaging (fMRI) while they viewed a set of emotional pictures and took verbal
      ratings of the emotional valence and arousal of each picture after scanning.
      Response-related multiple correlation analysis revealed differential brain
      activity in five brain regions. Startle reflex changes, associated with the
      valence of a stimulus, correlated with activity in the amygdala, while verbal
      reports of negative emotional valence varied with insular activity. Peripheral
      physiologic and verbal responses along the arousal dimension varied with thalamic
      and frontomedial activity. Peripheral physiologic responses along both dimensions
      correlated with activity in somatosensory association areas in the anterior
      parietal cortex. In the valence dimension, activity in the left anterior parietal
      cortex was associated with highly correlating peripheral physiologic and verbal
      responses, suggesting that verbal reports of emotional valence might depend
      partly on brain circuits representing peripheral physiologic changes. Our data
      provide direct evidence for a functional segregation of brain structures
      underlying peripheral physiologic responses and verbal ratings along the
      emotional dimensions of valence and arousal.

PMID- 15449357
TI  - Different roles of the frontal and parietal regions in memory-guided saccade: a
      PCA approach on time course of BOLD signal changes.
AB  - Although involvement of the frontoparietal regions in visually guided saccade and
      visuospatial attention has been established, functional difference of the frontal
      and parietal regions suggested in neuropsychological observations and lesion
      studies in animals has not been explicitly supported by functional imaging
      studies. Considering a possible disadvantage of cognitive subtraction in an
      interregional comparison, we directly compared the time course of BOLD signal
      changes across regions. Normal subjects performed a modified version of a memory
      guided saccade task in which saccade was performed both during encoding and
      execution phases. In addition, the delay period was fixed and the peripheral
      target was presented also during the execution phase together with distracters.
      Therefore, visuospatial representation was likely maintained in the sensory
      domain during the delay phase. A principal component analysis on the time-course
      data separated the 20 activated areas into three groups, which largely coincided
      with the cerebral lobes. The frontal group included the putative human FEF and
      SEF, and the parietal group PEF. The frontal and occipital groups exhibited the
      time course of activation with two peaks corresponding to neural responses during
      the encoding and execution phases, and the parietal group exhibited a single
      humped activation pattern corresponding to neural activity during the delay
      phase. The results suggest that the frontal regions are more associated with the
      execution of saccade, and the parietal regions with visuospatial representation,
      presumably in the sensory domain.

PMID- 15449356
TI  - Cortical activity to vibrotactile stimulation: an fMRI study in blind and sighted
      individuals.
AB  - Blind individuals show visual cortex activity during Braille reading. We examined
      whether such cross-modal activations reflect processing somatosensory stimuli
      independent of language by identifying cortical activity during a one-back
      vibrotactile matching task. Three groups (sighted, early-onset, and late-onset
      [>12 years] blind) detected whether paired vibrations (25 and 100 Hz), delivered
      to the right index finger, differed in frequency. Three successive paired
      vibrations, followed by a no-stimulation interval, were presented in a long event
      related design. A fixed effects average z-score analysis showed increased
      activity throughout the visuotopic visual cortex, where it was mostly restricted
      to foveal and parafoveal eccentricities. Early blind showed the most extensive
      distribution of activity. Late blind exhibited activity mostly in similar regions
      but with declining response magnitudes with age of blindness onset. Three sighted
      individuals had suprathreshold activity in V1 but negative responses elsewhere in
      visual cortex. Mixed effects ANOVA confirmed group distinctions in defined
      regions (V1, V3, V4v, V7, LOC, and MT). These results suggest cross-modal
      adaptation to tactile stimulation in visual cortex independent of language
      processes. All groups showed increased activity in left primary (S1) and
      bilateral second somatosensory areas, but without response magnitude differences
      between groups throughout sensorimotor cortex. Early blind showed the greatest
      spatial extent of S1 activity. Blind participants had more extensive bilateral
      activity in anterior intraparietal sulcus and supramarginal gyrus. Extensive
      usage of touch in Braille reading may underlie observed S1 expansions in the
      reading finger representation. In addition, learned attentiveness to touch may
      explain similar expansion of parietal tactile attention regions.

PMID- 15449358
TI  - Variability of fMRI activation during a phonological and semantic language task
      in healthy subjects.
AB  - Assessing inter-individual variability of functional activations is of practical
      importance in the use of functional magnetic resonance imaging (fMRI) in a
      clinical context. In this fMRI study we addressed this issue in 30 right-handed,
      healthy subjects using rhyme detection (phonologic) and semantic categorization
      tasks. Significant activations, found mainly in the left hemisphere, concerned
      the inferior frontal gyrus, the superior/middle temporal gyri, the prefrontal
      cortex, the inferior parietal lobe, the superior parietal lobule/superior
      occipital gyrus, the pre-central gyrus, and the supplementary motor area.
      Intensity/spatial analysis comparing activations in both tasks revealed an
      increased involvement of frontal regions in the semantic task and of temporo
      parietal regions in the phonologic task. The frequency of activation analyzed in
      nine regional subdivisions revealed a high inter-subject variability but showed
      that the most frequently activated regions were the inferior frontal gyrus and
      the prefrontal cortex. Laterality indices, strongly lateralizing in both tasks,
      were slightly higher in the semantic (0.76 +/- 0.19) than the phonologic task
      (0.66 +/- 0.27). Frontal dominance indices (a measure of frontal vs. posterior
      left hemisphere dominance) indicated more robust frontal activations in the
      semantic than the phonologic task. Our study allowed the characterization of the
      most frequently involved foci in two language tasks and showed that the
      combination of these tasks constitutes a suitable tool for determining language
      lateralization and for mapping major language areas.

PMID- 15449359
TI  - Neural systems for sign language production: mechanisms supporting lexical
      selection, phonological encoding, and articulation.
AB  - Overt production of ASL signs was evaluated using H(2)(15)O PET to differentiate
      brain systems that support sign language production at the lexical-selection and
      phonological-articulatory levels. Subjects were 16 right-handed, congenitally
      deaf native ASL signers (10 women, six men; age 20 to 29 years). Scans were
      performed while subjects (1) passively viewed ASL nouns, (2) repeated nouns, (3)
      generated verbs in response to these nouns, (4) passively viewed videotaped
      segments depicting transitive actions, and (5) generated a verb to describe these
      actions. Conjunctions between the two verb-generation tasks revealed left
      lateralized activation of perisylvian, frontal, and subcortical regions commonly
      observed in spoken language generation tasks and implicated in processes of
      semantic feature binding and lexical selection. Analysis of noun repetition minus
      viewing condition revealed activation of distinct systems supporting phonological
      encoding and articulation, including bilateral activation of sensorimotor areas
      and association cortices in the temporal, parietal, and occipital lobes. In
      addition, lexical-selection and articulatory processes were associated with
      activation of different corticostriatal-thalamocortical circuits: articulation
      with activation of the motor, and lexical-selection with activation of the
      prefrontal circuits, respectively. The results collectively provide insight into
      dissociable neural systems underlying these psycholinguistic functions. In
      addition, activation of regions that are typically associated with the auditory
      system during sign production suggests that these regions may support modality
      independent linguistic processes, or may indicate cross-modal plasticity within
      the deaf brain.

PMID- 15449360
TI  - Determining the hemispheric dominance of spatial attention: a comparison between
      fTCD and fMRI.
AB  - Human brain mapping allows the systematic assessment of interindividual
      differences in functional brain anatomy. Functional transcranial Doppler
      sonography (fTCD) is an imaging tool that allows for fast and mobile assessment
      of hemispheric lateralization of task-related brain activation. It is ideal to
      screen large cohorts of subjects. The goal of the present study was to
      investigate whether fTCD and functional magnetic resonance imaging (fMRI)
      determine hemispheric lateralization of brain activation related to visuospatial
      attention concordantly. Used together, fMRI and fTCD may then open up a wide
      range of potential applications in neuroscience. Fifteen subjects were examined
      both with fTCD and fMRI while they judged accuracy of line bisections (Landmark
      task). For fTCD, the maximal mean difference in stimulus-related relative
      cerebral blood flow velocity changes in the left and right middle cerebral
      arteries was assessed as the lateralization index LI(fTCD). For fMRI, two
      approaches were used to determine hemispheric dominance. First, we measured brain
      activity as the extent of the activated region, i.e., the number of activated
      voxels above a statistical threshold. Second, we calculated the magnitude of the
      fMRI signal change between the activation and the control task within a region of
      interest. Results of fTCD and fMRI were concordant in every single case.
      Therefore, scanning large cohorts with fTCD for hemispheric dominance during
      Landmark task will provide results consistent with fMRI. FMRI can then be used
      for in depth assessment of the specific patterns of activation.

PMID- 15449362
TI  - Intracranial volume in mild cognitive impairment, Alzheimer's disease and
      vascular dementia: evidence for brain reserve?
AB  - OBJECTIVE: The possibility of brain volume reserve effects was examined in a
      sample of geriatric outpatients with mild cognitive impairment (MCI), Alzheimer's
      disease (AD) and vascular dementia (VaD). The total intracranial volume (ICV)
      served as an estimate of the maximum attained brain volume in life. METHODS:
      Subjects (n = 181, mean age 60.7) were consecutive referrals to a geriatric
      outpatients clinic (n = 96) and a group of age-matched healthy control subjects
      (n = 85). ICV and brain volume were attained from T1-weighted magnetic resonance
      images using a stereological method. Hippocampal atrophy was assessed with a
      visual rating scale. RESULTS: ICV was significantly smaller in patients with AD
      and VaD than in control subjects, but effect size was small. After adjusting for
      age and gender, having ICV in the smallest quartile significantly increased the
      risk of cognitive impairment (either MCI or dementia). In patients with dementia,
      but not in MCI, severity of cognitive impairment and ICV were moderately
      correlated. The effect of ICV on cognition was not mediated by hippocampal
      atrophy. CONCLUSIONS: These findings are compatible with volume reserve effects
      that modify the clinical expression of symptoms in both AD and VaD. They may have
      implications for the design of neuroimaging studies that use ICV for
      normalization procedures.

PMID- 15449363
TI  - An open trial of venlafaxine for the treatment of late-life atypical depression.
AB  - OBJECTIVES: The atypical subtype in patients with major depressive disorder is
      characterized by mood reactivity, significant weight gain or increase in
      appetite, hypersomnia, leaden paralysis and a long-standing pattern of
      interpersonal rejection sensitivity. Though atypical depression is well
      documented in younger patients, little attention has been paid to the atypical
      subtype in samples of late-life depressed patients. This study reports the
      patient characteristics and treatment results of an eight-week open-label trial
      of venlafaxine in a sample of older depressed patients with atypical subtype.
      METHODS: Patients received fixed dosing schedule (up to 300 mg/day) of
      venlafaxine (Effexor XR) for 8 weeks. RESULTS: In this sample of 17 patients, the
      mean age was 65.6 years and 77% were female. Most strikingly, 53% of patients
      presented with late-onset atypical depression defined as first episode after the
      age of 50. Fifteen of the 17 patients (88%) completed the eight-week treatment
      trial. The mean score on the HRSD 24-item decreased from 22.2 +/- 5.1 at baseline
      to 11.8 +/- 8.9 (p<0.001), and the mean total atypical item score decreased from
      6.2 +/- 1.6 to 2.8 +/- 2.0 (p < 0.001). Remission was defined as a final HRSD <
      or = 10 and a 50% reduction in baseline HRSD score. The intent-to-treat remission
      rate was 65% and the completer remission rate was 73%. CONCLUSIONS: In this
      sample of late-life patients with atypical depression venlafaxine treatment was
      reasonably effective and well tolerated. However, the effectiveness of
      venlafaxine in this study must be considered in the context that this was an open
      trial of antidepressant medication. Insufficient attention has been given to the
      atypical subtype in late-life depression. Whether late-onset atypical depression
      is significantly different from early-onset atypical depression, and whether late
      onset patients with atypical depression are significantly different from late
      onset patients with other depressive subtypes are questions of compelling
      interest.

PMID- 15449364
TI  - Use of constraints and their correlates in Norwegian nursing homes.
AB  - OBJECTIVE: To analyse the effect of patient and ward characteristics on the use
      of constraints in nursing homes. METHOD: Primary carers in 222 wards in Norwegian
      nursing homes were asked about use of constraints towards 1926 patients during
      seven days. Constraints were grouped as mechanical restraints, non-mechanical
      restraints, electronic surveillance, force or pressure in medical examination or
      treatment, and force or pressure in ADL. The patients' mental capacity (CDR
      score), activity in daily living (ADL) and behaviour (BARS score) were rated.
      Type and size of ward, staffing level and educational level of the staff was
      recorded. RESULTS: In all 758 of the patients were subjected to any constraint.
      Degree of dementia, aggressive behaviour and loss of function in ADL had
      significant impact on all types of constraint except for electronical
      surveillance. The strongest associations were found between degree of dementia
      and mechanical restraint (OR 5.14), impaired ADL and mechanical restraint (OR
      9.23) and aggression and force or pressure in ADL (OR 3.75). Mechanical restraint
      was less used towards patients in special care units for persons with dementia
      (SCU) (OR 0.38) compared to patients in regular units (RU), whereas non
      mechanical restraint was more frequent used in SCUs (OR 2.28). Type of ward had
      no significant impact on use of other types of constraints. Staff level and
      education level of the staff had no significant impact on the use of constraint.
      CONCLUSION: Constraint is frequently used in nursing homes, and most frequent
      toward patients with severe dementia, aggressive behaviour or low ADL function.

PMID- 15449365
TI  - Vulnerability to post-traumatic stress disorder and psychological morbidity in
      aged holocaust survivors.
AB  - OBJECTIVE: Although high rates of post-traumatic stress disorder (PTSD) and
      psychological morbidity have been consistently reported in Holocaust survivors
      (HS), reports are inconsistent about which factors are associated with
      psychological morbidity. In a study of the oldest HS cohort yet reported, we aim
      to clarify why this variability exists by examining factors associated with PTSD
      and psychological morbidity, including for the first time measures of personality
      and defense mechanisms. METHODS: One hundred HS randomly selected from a
      convenience sample of 309 respondents to a survey of Jewish persons aged 60 years
      and older living in the community in Sydney were assessed using the following
      instruments: demographics, severity of trauma experienced, General Health
      Questionnaire (GHQ-28), PTSD diagnosis (DSM-IV), Brief Psychiatric Rating Scale,
      Impact of Events Scale, Defense Style Questionnaire, modified Eysenck Personality
      Inventory. RESULTS: Older age, experience of more severe trauma, use of immature
      defense mechanisms and higher neuroticism were associated with significant PTSD
      and psychological morbidity; severity of trauma was associated with PTSD and with
      more severe psychological morbidity. CONCLUSIONS: A profile of survivors at-risk
      can be identified that may have application to survivors of more recent
      holocausts. Late life may be a period of vulnerability in the aftermath of severe
      trauma.

PMID- 15449366
TI  - Conversion pseudodementia in older people: a descriptive case series.
AB  - METHODS: This paper reports a case series of ten patients collected over a 12
      year period of clinical work in old age psychiatry in the UK by the author.
      RESULTS: The core features of the syndrome are: apparent cognitive impairment,
      regression and increasing physical dependency beginning in late middle or early
      old age, without evidence for an organic dementia from investigations or from
      taking into account the course of the illness. The syndrome is more common in
      women from a higher socio-economic background with past psychiatric histories
      dominated by depressive symptoms. The syndrome usually progresses to the point
      where long term institutional care is needed although the mean survival from
      onset is 13 years. CONCLUSIONS: The author suggests that conversion
      pseudodementia in older people is caused by a catastrophic reaction to cumulative
      loss in later life in individuals who have predisposing borderline and
      narcissistic personality traits. Treatment using psychotherapeutic approaches may
      limit the progression of the syndrome if it is recognised at an early stage.

PMID- 15449367
TI  - Potential treatment effects of donepezil not detected in Alzheimer's disease
      clinical trials: a physician survey.
AB  - OBJECTIVES: Clinical trials of the cholinesterase inhibitor donepezil have used
      standard psychometric tools to evaluate treatment efficacy. These trials,
      however, appear not to capture clinically demonstrable, but otherwise unmeasured,
      beneficial treatment effects. We sought to identify and categorize clinically
      recognizable effects of donepezil treatment in Alzheimer's disease. METHODS: A
      list of potential effects was developed using clinical trials data and the
      experience of an expert panel. These were incorporated in a questionnaire, which
      was tested with a focus group, revised and then used in a postal survey of
      physicians. Data were classified by cognitive domain, and reviewed by a second
      panel. RESULTS: Items that were most often rated as being improved were related
      to frontal systems function, including attentional capacity and initiative.
      Behavioral symptoms that were among the highest rated items were apathy, mood,
      and agitation. The top two other items were social interactions and involvement
      in domestic activities. Of the top ten symptomatic treatment effects, only four
      appeared to be readily identified by current standard measures. CONCLUSIONS:
      Physicians recognize as important several treatment effects that are not well
      captured by current standard measures. New methods are needed to capture such
      effects, which also have the potential to offer insight into the neurobiology of
      the human cholinergic system.

PMID- 15449368
TI  - The sense of coherence, burden, and depressive symptoms in informal caregivers
      during the first month after stroke.
AB  - BACKGROUND: Individuals with a strong sense of coherence (SOC), which considers
      one's ability to respond to stressors by the appropriate use of adaptive coping
      resources, can avoid breakdown when confronted with stress. This study examined
      the associations between SOC, perceived burden (caregiver's perception of the
      effect of caregiving-related stress) and depressive symptoms of informal
      caregivers (family members and involved friends) of stroke survivors one-month
      after the stroke. METHODS: One-hundred and four ethnically diverse veterans who
      were hospitalized after experiencing an acute stroke and their informal
      caregivers were enrolled in the study prior to discharge. One-month after being
      discharged from one of five Veterans Affairs Medical Centers in Florida and
      Puerto Rico, comprehensive data was collected and analyzed. RESULTS: Multiple
      regression analyses showed that greater SOC was associated with both lower burden
      (p < 0.0001) and fewer depressive symptoms (p < 0.0001). Higher caregiver burden,
      in turn, was significantly associated with more depressive symptoms (p = 0.003).
      However, when depressive symptoms was regressed on both SOC and burden jointly,
      the previously significant association between burden and depressive symptoms was
      no longer significant (p = 0.80) and SOC was still strongly associated with fewer
      depressive symptoms (p < 0.0001). CONCLUSIONS: Determining factors that may
      lessen burden and depressive symptoms for caregivers of stroke survivors during
      the transition period after discharge to their residence are imperative for
      developing successful interventions. SOC appears to be an important response in
      alleviating the levels of perceived burden and especially in depressive symptoms.

PMID- 15449369
TI  - Medical comorbidity in late-life depression.
AB  - OBJECTIVES: Medical comorbidity is common in elderly patients with depression,
      however the difference between depressed and non-depressed elderly populations is
      not well established. Additionally, differences between subgroups of depressed
      populations, including those with MRI-defined vascular depression and those with
      late-onset compared with early-onset depression are not well described. METHODS:
      We compared self-report of medical disorders between 370 depressed elders and 157
      non-depressed control subjects. Subjects were additionally dichotomized based on
      presence or absence of subcortical MRI lesions and age of onset. Medical
      comorbidity was assessed by self report only, and depressed subjects were
      additionally assessed by the clinician-rated Cumulative Illness Rating Scale.
      RESULTS: When compared with the non-depressed group, depressed subjects were
      significantly more likely to report the presence of hypertension, heart disease,
      gastrointestinal ulcers, and 'hardening of the arteries'. Analyses of subjects
      with subcortical disease demonstrated they were significantly older, more likely
      to have depression, and more likely to report the presence of hypertension.
      Finally, the depressed cohort with late-onset depression (occurring after age 50
      years) had more male subjects, exhibited greater CIRS scores, and greater
      prevalence of hypertension, but these did not reach a level of statistical
      significance after applying a Bonferroni correction. CONCLUSIONS: Vascular
      comorbidities are common in depressed elders. The differences in the report of
      hypertension supports past work investigating a vascular contribution to late
      life depression. Given the association between depression and poor medical
      outcomes of cardiac disease, this population deserves clinical scrutiny and
      further research.

PMID- 15449371
TI  - Assessment of cognitive function in older hospital inpatients: is the Telephone
      Interview for Cognitive Status (TICS-M) a useful alternative to the Mini Mental
      State Examination?

PMID- 15449370
TI  - Prevalence and patterns of executive impairment in community dwelling Mexican
      Americans: results from the Hispanic EPESE Study.
AB  - INTRODUCTION: Little is known about the prevalence of impaired executive control
      function (ECF) in community dwelling elderly or minority populations. We have
      determined the prevalence of cognitive impairment and impaired ECF in a community
      dwelling Mexican American elderly population, and their associations with
      functional status. SUBJECTS: Subjects were 1165 Mexican Americans age 65 and over
      who were administered CLOX as part of the third wave of the Hispanic Established
      Population for Epidemiological Study (HEPESE) conducted from 1998 to 1999.
      METHODS: ECF was measured by an executive clock-drawing task (CDT) (i.e. CLOX1).
      Non-executive cognitive function was assessed by the Mini-Mental State
      Examination (MMSE) and a non-executive CDT (CLOX2). CLOX scores were combined to
      estimate the prevalence of global CLOX failure (i.e. 'Type 1' cognitive
      impairment) vs isolated CLOX1 failure (i.e. Type 2 cognitive impairment).
      RESULTS: 59.3% of subjects failed CLOX1. 31.1% failed both CLOX1 and CLOX2 (Type
      1 cognitive impairment). 33.3% failed CLOX1 only (Type 2 cognitive impairment).
      35.6% passed both measures [no cognitive impairment (NCI)]. Many subjects with
      CLOX1 impairment at Wave 3 had normal MMSE scores. This was more likely to occur
      in the context of Type 2 cognitive impairment. Both CLOX defined cognitive
      impairment groups were associated with functional impairment. CONCLUSIONS: A
      large percentage of community dwelling Mexican American elderly suffer cognitive
      impairment that can be demonstrated through a CDT. Isolated executive impairments
      appear to be most common. The ability of a CDT to demonstrate ECF impairments
      potentially offers a rapid, culturally unbiased and cost-effective means of
      assessing this domain. In contrast, the MMSE is relatively insensitive to ECF
      assessed by CLOX1.

PMID- 15449372
TI  - Identification of a novel protein D3UPCA from Halobacterium salinarum and
      prediction of its function.
AB  - Halobacterium salinarum is an extremely halophilic archaea, which is able to live
      in highly saline environments. In a recent study, several halophilic archaea were
      found to have the ability to biodegrade organic hydrocarbon pollutants, but
      protein information regarding hydrocarbon degradation and tolerance in halophilic
      archaea has been relatively rare. In this study, the protein expression profile
      of H. salinarum cultured under different diesel concentrations (0, 2 and 4%) was
      investigated by two-dimensional gel electrophoresis. Proteins which increased
      their expression levels in diesel media were identified using matrix-assisted
      laser desorption/ionization-time of flight and electrospray ionization-tandem
      mass spectrometry analysis. Among these, a protein spot (named D3UPCA) which was
      up-regulated about nine-fold and found to have COG3388, an uncharacterized
      protein conserved in archaea, was selected in order to further characterize its
      functions. The D3UPCA coding gene (named d3upca) was cloned and expressed in
      Escherichia coli, and purified by the glutathione-S-transferase-fusion method.
      The function of the protein was estimated using various bioinformatics tools and
      was predicted to be related to the regulation of transcription and/or translation
      of genes needed to tolerate stresses associated within the presence of diesel
      oil.

PMID- 15449373
TI  - Proteome analysis of Pseudomonas sp. K82 biodegradation pathways.
AB  - Pseudomonas sp. K82 is a soil bacterium that can degrade and use monocyclic
      aromatic compounds including aniline, 3-methylaniline, 4-methylaniline, benzoate
      and p-hydroxybenzoate as its sole carbon and energy sources. In order to
      understand the impact of these aromatic compounds on metabolic pathways in
      Pseudomonas sp. K82, proteomes obtained from cultures exposed to different
      substrates were displayed by two-dimensional gel electrophoresis and were
      compared to search for differentially induced metabolic enzymes. Column
      separations of active fractions were performed to identify major biodegradation
      enzymes. More than thirty proteins involved in biodegradation and other types of
      metabolism were identified by electrospray ionization-quadrupole time of flight
      mass spectrometry. The proteome analysis suggested that Pseudomonas sp. K82 has
      three main metabolic pathways to degrade these aromatic compounds and induces
      specific metabolic pathways for each compound. The catechol 2,3-dioxygenase
      (CD2,3) pathway was the major pathway and the catechol 1,2-dioxygenase (beta
      ketoadipate) pathway was the secondary pathway induced by aniline (aniline
      analogues) exposure. On the other hand, the catechol 1,2-dioxygenase pathway was
      the major pathway induced by benzoate exposure. For the degradation of p
      hydroxybenzoate, the protocatechuate 4,5-dioxygenase pathway was the major
      degradation pathway induced. The nuclear magnetic resonance analysis of
      substrates demonstrated that Pseudomonas sp. K82 metabolizes some aromatic
      compounds more rapidly than others (benzoate > p-hydroxybenzoate > aniline) and
      that when combined, p-hydroxybenzoate metabolism is repressed by the presence of
      benzoate or aniline. These results suggest that proteome analysis can be useful
      in the high throughput study of bacterial metabolic pathways, including that of
      biodegradation, and that inter-relationships exist with respect to the metabolic
      pathways of aromatic compounds in Pseudomonas sp. K82.

PMID- 15449374
TI  - Differential expression profiling of the proteomes and their mRNAs in porcine
      white and red skeletal muscles.
AB  - Skeletal muscle is an heterogeneous tissue with various biochemical and physical
      properties of several fiber types. In this study, we carried out the comparative
      study of protein expression patterns in white and red muscles using two
      dimensional gel electrophoresis (2-DE). From more than 500 protein spots detected
      on each 2-DE gel, we screened five proteins that were differentially expressed
      between white and red muscles. Using peptide mass fingerprint and tandem mass
      spectrometry analysis these proteins were identified as myoglobin, two slow
      twitch isoforms of myosin light chain and two small heat shock proteins (HSP20
      and HSP27). The protein levels of myoglobin, myosin light chain and HSP20 were
      higher in red muscle, whereas HSP27 was higher in white muscle. In addition,
      genes of the identified proteins were cloned and their mRNAs were examined.
      Positive correlations between protein content and their mRNA levels were observed
      in white and red muscle. These results may provide us with valuable information
      to understand the different expression profiling between white and red muscle at
      the protein level.

PMID- 15449375
TI  - Identification of oxidized mitochondrial proteins in alcohol-exposed human
      hepatoma cells and mouse liver.
AB  - Heavy alcohol consumption can damage various cells and organs partly through
      production of reactive oxygen species (ROS) and mitochondrial dysfunction.
      Treatment with antioxidants can significantly reduce the degree of damage.
      Despite well established roles of ROS in alcohol-induced cell injury, the
      proteins that are selectively oxidized by ROS are poorly characterized. We
      hypothesized that certain cysteinyl residues of target proteins are oxidized by
      ROS upon alcohol exposure, and these modified proteins may play roles in
      mitochondrial dysfunction. A targeted proteomics approach utilizing biotin-N
      maleimide (biotin-NM) as a specific probe to label oxidized cysteinyl residues
      was employed to investigate which mitochondrial proteins are modified during and
      after alcohol exposure. Human hepatoma HepG2 cells with transduced CYP2E1 (E47
      cells) were used as a model to generate ROS through CYP2E1-mediated ethanol
      metabolism. Following exposure to 100 mM ethanol for 4 and 8 h, the biotin-NM
      labeled oxidized proteins were purified with agarose coupled to either
      streptavidin or monoclonal antibody against biotin. The purified proteins were
      resolved by two-dimensional gel electrophoresis and protein spots that displayed
      differential abundances were excised from the gel, in-gel digested with trypsin
      and analyzed for identity utilizing either matrix-assisted laser desorption-time
      of flight mass spectrometry or microcapillary reversed-phase liquid
      chromatography-tandem mass spectrometry. The results demonstrate that heat shock
      protein 60, protein disulfide isomerase, mitochondrial aldehyde dehydrogenases,
      prohibitin, and other proteins were oxidized after alcohol exposure. The identity
      of some of the proteins purified with streptavidin-agarose was also confirmed by
      immunoblot analyses using the specific antibody to each target protein. This
      method was also used to identify oxidized mitochondrial proteins in the alcohol
      fed mouse liver. These results suggest that exposure to ethanol causes oxidation
      of various mitochondrial proteins that may negatively affect their function and
      contribute to alcohol-induced mitochondrial dysfunction and cellular injury.

PMID- 15449376
TI  - Identification of B-cell translocation gene 1 as a biomarker for monitoring the
      remission of acute myeloid leukemia.
AB  - Acute myeloid leukemia (AML) is a biologically heterogeneous disease of the
      hematopoietic system characterized by a clonal accumulation of immature blast
      cells in bone marrow. We used a proteomic approach based on two-dimensional
      electrophoresis and mass spectrometry to search for biomarkers related to the
      complete remission (CR) state of AML patients. We detected one AML-related
      protein, which was identified as the B-cell translocation gene 1 (BTG1) protein
      that belongs to anti-proliferative protein family. In the CR state of AML-M2 and
      M3 patients (by French-American-British subtype classification), the BTG1 protein
      was upregulated in bone marrow mononuclear cells. It was also expressed robustly
      in normal bone marrow mononuclear cells. In addition, the BTG1 levels in AML-M2
      patients in a non-remission state after therapy did not increase as they did
      before therapy. Overexpression of BTG1 mRNA was also observed in the CR state of
      all-trans-retinoic acid (ATRA)-treated AML-M3 patients and ATRA-treated HL-60
      cells. Taken together, these results suggest that BTG1 may play a role in the
      differentiation process of myeloid cells and can therefore be used as a potential
      treatment-related biomarker for monitoring the remission status of AML-M2 and M3
      patients.

PMID- 15449377
TI  - Identification of antigenic proteins from Neospora caninum recognized by bovine
      immunoglobulins M, E, A and G using immunoproteomics.
AB  - Antigenic proteins of Neospora caninum (N. caninum) against bovine
      immunoglobulins M, E, A, and G were investigated by using immunoproteomics.
      Proteins of N. caninum (KBA-2) tachyzoite lysates separated by two-dimensional
      gel electrophoresis were transferred to polyvinylidene difluoride (PVDF)
      membranes, probed with different bovine immunoglobulin class and classified.
      Antigenic spots recognized were also identified by matrix-assisted laser
      desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS) analysis.
      132, 84, 4, and 40 antigenic protein spots were recognized on N. caninum
      immunoblot profiles against bovine IgM, IgE, IgA, and IgG, respectively. Of these
      protein spots, the antigenic proteins recognized by either IgM, IgE, and IgG, or
      IgM and IgG were HSP70, pyruvate kinase, actin, NCDG-1, tubulin alpha-chain, and
      putative ribosomal protein S2. On the other hand, IgM, IgE, and IgA reacted with
      NTPase, HSP60, tubulin beta-chain, putative protein disulfide isomerase, enolase,
      lactate dehydrogenase, serine-threonine phosphatase, 14-3-3 protein homologue,
      and GRA2 protein. Most of the antigenic proteins identified were associated with
      the process of invasion, proliferation, and egression of apicomplexans. In our
      study, HSP70, actin, NTPase, HSP60, pyruvate kinase, enolase, putative ribosomal
      protein S2, NCDG-1, and GRA2 proteins were found to be immunodominant proteins,
      which may contribute to the development of diagnostic markers and vaccine.

PMID- 15449378
TI  - A simple pattern classification method for alcohol-responsive proteins that are
      differentially expressed in mouse brain.
AB  - Proteomic analysis of brain tissues obtained from two inbred mice, C57BL/6J (B6,
      an alcohol-preferring strain) and DBA/2J (D2, an alcohol-avoiding strain), that
      were orally administered 1.5 g/kg ethanol, was performed to investigate alcohol
      responsive proteins. To analyze relationships of alcohol-responsive protein spots
      between B6 and D2 mice, we have developed a simple spot classification method
      (SCM) for the fully matched spot data sets produced by the Melanie 4 analysis
      software using the paired two-dimensional (2-D) gels of two strains over time. By
      applying SCM, 55 protein spots that were differentially expressed in brain tissue
      were classified into 16 patterns as mirror images (2x8 patterns), and
      additionally in an ordered fashion such as 'fast turn over' and 'slow turn over'
      forms, depending on the frequency of repetition and rate of changed expression
      profile in 2-D gels over time. Searching for any interaction proteins through
      databases of interacting proteins using the classified data set has led to the
      construction of a linkage map, which reveals the interrelationship of the alcohol
      responsive proteins between different species. Thus, it is suggested that the
      different responses for alcohol between B6 and D2 may come from differences of
      the response rates and interactions of different variants of the alcohol
      responsive protein family.

PMID- 15449379
TI  - Comparative proteome analysis of differentially expressed proteins induced by K+
      deficiency in Arabidopsis thaliana.
AB  - Mineral nutrient deficiencies constitute major limitations for plant growth on
      agricultural soils around the world. To identify genes that possibly play roles
      in plant K(+) nutrition, we employed the comparative proteome analysis for
      proteins isolated from Arabidopsis seedlings treated with K(+) deficiency for 3 h
      and 7 d. We identified genes including those encoding putative transcription
      factors, protein kinases, and phosphatases, proteins involved in phytohormone
      biosynthesis or signaling, proteins involved in carbon and energy metabolism, and
      other proteins possibly involved in signal transduction pathway such as 14-3-3
      proteins and small G-protein. Our results suggest that those proteins may play
      roles in signal transduction pathways linking changes in extracellular K(+)
      status to alterations in gene expression facilitating K(+) homeostasis. These
      results yield a comprehensive picture of the post-transcriptional response for
      deprivation of K(+) and serve as a basic platform for further characterization of
      gene function and regulation in plant mineral nutrition.

PMID- 15449380
TI  - Identification of proteins regulated by interferon-alpha in resistant and
      sensitive malignant melanoma cell lines.
AB  - Treatment of patients with malignant melanoma with interferon-alpha achieves a
      response in a small but significant subset of patients. Currently, although much
      is known about interferon biology, little is known about either the particular
      mechanisms of interferon-alpha activity that are crucial for response or why only
      some patients respond to interferon-alpha therapy. Two melanoma cell lines (MeWo
      and MM418) that are known to differ in their response to the antiproliferative
      activity of interferon-alpha, have been used as a model system to investigate
      interferon-alpha action. Using a proteomics approach based on two-dimensional
      polyacrylamide gel electrophoresis and mass spectrometry, several proteins
      induced in response to interferon-alpha have been identified. These include a
      number of gene products previously known to be type I interferon responsive
      (tryptophanyl tRNA synthetase, leucine aminopeptidase, ubiquitin cross-reactive
      protein, gelsolin, FUSE binding protein 2 and hPNPase) as well as a number of
      proteins not previously reported to be induced by type I interferon (cathepsin B,
      proteasomal activator 28alpha and alpha-SNAP). Although the proteins upregulated
      by interferon-alpha were common between the cell lines when examined at the level
      of Western blotting, the disparity in the basal level of cathepsin B was
      striking, raising the possibility that the higher level in MM418 may contribute
      to the sensitivity of this cell line to interferon-alpha treatment.

PMID- 15449381
TI  - [How often does a malignant lentigo develop from a precursor lesion?].

PMID- 15449382
TI  - Syringomyelia in twin brothers discordant for Chiari I malformation: case report.
AB  - Familial syringomyelia outside of trauma, tumor, or infection has been reported.
      Cases are presented that highlight the possible connection between familial
      syringomyelia and the Chiari 0 malformation. We report on 11-year-old twin
      brothers both with syringomyelia. Magnetic resonance imaging further revealed
      that one brother had Chiari I malformation and the other had Chiari 0
      malformation. Both underwent posterior fossa decompression with radiologic
      improvement of their syringes. These case reports lend credence to earlier
      reports of improvement in syringomyelia following posterior fossa decompression
      in the absence of Chiari I malformation, the so-called Chiari 0 malformation. In
      addition, these case reports should influence the manner in which familial
      syringomyelia without tonsillar ectopia is defined and addressed, that is,
      posterior fossa decompression versus shunting of the syrinx, thereby addressing
      the potential cause of the syringomyelia and not only the enlarged cavity itself.

PMID- 15449383
TI  - [Thermal knowledge and therapies: a comparative view of Portugal (Sao Pedro do
      Sul hot springs) and Brazil (Caldas da Imperatriz hot springs)].
AB  - Based on nineteenth - and twentieth-century texts, the article discusses how
      medicine legitimized the therapeutic practice of thermalism as so-called
      'scientific' knowledge, with the creation of therapeutic establishments and hot
      springs resort. My research began in Portugal in 1996, where I produced an
      ethnography of experiences at the Sao Pedro do Sul hot springs. My research at
      Brazil's Caldas da Imperatriz, initiated in August 2001, is still underway.

PMID- 15449384
TI  - [Health and Angola's Companhia de Diamantes].
AB  - Ever more studies have been devoted to the use of medicine in colonial contexts,
      a topic that serves to illustrate the more subtle ways in which a colonial State
      may spread its power. Countering the studies of colonial mining companies
      conducted to date, the case of the Companhia de Diamantes de Angola (Diamang)
      brings something new to the issue of colonial relations. Diamang was
      extraordinarily cautious when it came to the health of its workers and local
      population. However, this sanitary vigilance was closely linked to company
      concerns about productivity and about the need to constantly enhance human
      resource management.

PMID- 15449385
TI  - Introduction: A cloud over history.

PMID- 15449386
TI  - Ecologies of complexity: Tropical environments, African trypanosomiasis, and the
      science of disease control in British colonial Africa, 1900-1940.
AB  - Tropical Africa was one of the last regions of the world to experience formal
      European colonialism, a process that coincided with the advent of a range of new
      scientific specialties and research methods. The history of British attempts to
      understand and control African trypanosomiasis (sleeping sickness in humans and
      nagana in cattle), following the intense human epidemics that broke out between
      1895 and 1910, reveals hitherto ignored scientific research in the fields of
      ecology, epidemiology, and tropical medicine that helped produce a new
      understanding of the "ecology of disease." Often generated within a transnational
      and inter-disciplinary context, this knowledge increasingly assumed that vector
      borne diseases in tropical environments were highly complex, dynamic, and
      interrelated phenomena. Thus while many people continued to hope that
      trypanosomiasis could be eradicated, research results made this prospect seem
      unlikely, if not impossible.

PMID- 15449387
TI  - Enteral feeding in patients with advanced dementia.

PMID- 15449388
TI  - Natural histories of infectious disease: ecological vision in twentieth-century
      biomedical science.
AB  - During the twentieth century, disease ecology emerged as a distinct disciplinary
      network within infectious diseases research. The key figures were Theobald Smith,
      F. Macfarlane Burnet, Rene Dubos, and Frank Fenner. They all drew on Darwinian
      evolutionism to fashion an integrative (but rarely holistic) understanding of
      disease processes, distinguishing themselves from reductionist "chemists" and
      mere "microbe hunters." They sought a more complex, biologically informed
      epidemiology. Their emphasis on competition and mutualism in the animated
      environment differed from the physical determinism that prevailed in much medical
      geography and environmental health research. Disease ecology derived in part from
      studies of the interaction of organisms - micro and macro - in tropical medicine,
      veterinary pathology, and immunology. It developed in postcolonial settler
      societies. Once a minority interest, disease ecology has attracted more attention
      since the 1980s for its explanations of disease emergence, antibiotic resistance,
      bioterrorism, and the health impacts of climate change.

PMID- 15449389
TI  - PEG placement in patients with dementia: a contentious ethical and clinical
      dilemma?

PMID- 15449390
TI  - Endoscopic Doppler US.

PMID- 15449391
TI  - The scale politics of emerging diseases.
AB  - The concept of scale politics offers historians a useful framework for analyzing
      the connections between environment and health. This essay examines the public
      health campaign around emerging diseases during the 1990s, particularly the ways
      in which different actors employed scale in geographic and political
      representations; how they configured cause, consequence, and intervention at
      different scales; and the moments at which they shifted between different scales
      in the presentation of their arguments. Biomedical scientists, the mass media,
      and public health and national security experts contributed to this campaign,
      exploiting Americans' ambivalence about globalization and the role of modernity
      in the production of new risks, framing them in terms that made particular
      interventions appear necessary, logical, or practical.

PMID- 15449392
TI  - Gender and the economy of health on the Santa Fe Trail.
AB  - Correspondence surrounding the death from consumption of a New England woman on
      the Santa Fe Trail in 1857 demonstrates how gender roles and economic network
      influenced health travel and the search for healthy places in the nineteenth
      century United States. Women did travel seeking healing or relief from sickness -
      sometimes, as here, in arduous, overland trips - but in ways subtly different
      from male health seekers: family attachments, as well as their own health
      concerns, impelled and justified women in their decisions to take journeys. Yet
      for women as for men, decisions about health travel were also bound up with the
      economic considerations that shaped their families' lives.

PMID- 15449394
TI  - Bibliography. Current world literature. Cancer in AIDS.

PMID- 15449393
TI  - Geographies of hope: mining the frontiers of health in Denver and beyond, 1870
      1965.
AB  - Across the western landscape of the United States, health was a natural resource,
      mined and sold by late-nineteenth and twentieth-century town boosters and
      physicians to those afflicted with chronic pulmonary illnesses such as
      tuberculosis and asthma. Regional economies of health were built upon climate and
      sunshine. After the Second World War, children, rather than nature, increasingly
      became a vital resource upon which institutions such as Denver's Jewish National
      Home for Asthmatic Children expanded the economic networks through which capital
      and drugs flowed. Despite these changes, the material traces of past landscapes
      lingered and resurfaced in the reconfigured places where hope dwelled.

PMID- 15449395
TI  - Bibliography. Current world literature. Gynecologic cancer.

PMID- 15449396
TI  - "Living is for everyone": border crossings for community, environment, and
      health.
AB  - This article examine the transnational networking practices fo Teresa Leal, an
      environmental justice activist living and working on the U.S.-Mexico border. It
      shows, through the method of engaged ethnography, how she and other community
      activists respond to the effects of global economic restructuring policies such
      as NAFTA. Grounded in an ecological epistemology, Lead blends "local" and
      "scientific" knowledges about the deteriorating health, economic, and
      environmental conditions at the border and constructs a "global sense of place"
      that brings into focus the everyday realities of neoliberal globalization. The
      article documents a daylong "toxic tour" of the Ambos Nogales region and
      highlights the multiple border crossings (epistemic, geographic, political,
      cultural) undertaken by Leal, other activists, and the author, a visitor to the
      region, to narrate a history of community health and environmental action in a
      transnational context.

PMID- 15449397
TI  - [Reply to the commentary to "The postnatal development of the frontal axial angle
      of the occipito-atlas complex C0/C1" ].

PMID- 15449398
TI  - Embryonal risks in gestational diabetes mellitus.
AB  - Diabetes mellitus is generally associated with a higher incidence of early
      pregnancy loss and congenital anomalies, though this relationship should be
      strictly restricted to patients with previously existing diabetes. In gestational
      diabetes mellitus, which often develops during the third trimester, no such
      relationship should exist, though the birth of a previous infant with a
      congenital anomaly is often assumed to be a risk factor for gestational diabetes.
      OBJECTIVE: The study attempts to analyse the congenital anomaly rate in women
      with gestational diabetes and compare this to the rates in women known to have
      normal glucose tolerance. RESULTS: The prevalence of infants/fetuses with
      congenital anomalies born to women with gestational diabetes amounted to 4.48%, a
      rate similar to that recorded in women with normal glucose tolerance (4.54%).
      CONCLUSIONS: The development of gestational diabetes, in contrast to pre-existing
      diabetes, does not appear to be associated with an increased risk for
      teratogenesis.

PMID- 15449399
TI  - The nature of touch in mothers experiencing maternity blues: the contribution of
      parity.
AB  - BACKGROUND: Maternal touch (MT) is an essential part of the initial contact
      between the mother and her newborn and has developmental effects on the child. MT
      is known to be reduced in postpartum depression (PPD). The nature of MT in
      mothers experiencing maternity blues and the effect of parity are still unknown.
      STUDY DESIGN: Seventy-five mothers were recruited from the ongoing series of
      deliveries. SUBJECTS: The participating mothers were observed during interaction
      with their newborns on the second-day postpartum. Touching behavior was scored on
      line according to the Touch Scoring Instrument, which includes nine types of MT.
      Mothers were categorized as exhibiting maternal blues according to Stein's
      depression scale. OUTCOME MEASURE: Touch Scoring Instrument. RESULTS: Primiparous
      mothers with blues avoided all types of touch whereas multiparous mothers with
      blues provided firm touch and holding. All mothers with blues avoided
      proprioceptive touch. Multiparous mothers without maternal blues provided various
      types of touch including affectionate holding and matter-of-fact touch whereas
      primiparous mothers without blues mostly provided holding. CONCLUSIONS: Mothers
      with maternity blues on day 2 exhibited a pattern of MT similar to that known to
      characterize postpartum depression. Mothers without blues are able to provide
      developmental touch in a manner known to facilitate CNS stability and newborn
      adjustment to the extra-uterine world. Parity modulates the effect of maternity
      blues on MT and buffers the withdrawal effect of depression. Maternal touch could
      be used as a diagnostic tool for detection of mothers at risk in a timely manner.
      Touch interventions, which were previously demonstrated in PPD mothers, may be
      utilized in an earlier stage postpartum.

PMID- 15449400
TI  - Corticotropin-releasing hormone peptide and human first-trimester placental
      growth.
AB  - The aim of this study was to determine whether corticotropin-releasing hormone
      (CRH) regulates human trophoblast cell growth. The results showed that exogenous
      CRH significantly stimulated human trophoblast proliferation in first-trimester
      primary cultures. In vivo, CRH was strongly immunolocalised to cytotrophoblastic
      cells in proliferative cell columns and in chorionic villi. We postulate that CRH
      may have an important role in early placental development and successful
      pregnancy.

PMID- 15449401
TI  - John Carew Eccles, Nobel Laureate (1903-1997).

PMID- 15449402
TI  - Pragmatics of implementing guidelines on the front lines.

PMID- 15449403
TI  - Pharmacogenetics: ethical issues.

PMID- 15449404
TI  - Tailor-made pharmacotherapy: future developments and ethical challenges in the
      field of pharmacogenomics.
AB  - Pharmacogenomics is the study of the myriad interactions between genes and
      pharmacotherapy. Developments in pharmacogenomics have changed and will affect
      pharmaceutical research, drug development and the practice of medicine in a
      significant way. In this article, we make an inventory of the ethical
      implications that might arise as a result of possible developments in
      pharmacogenomics and investigate whether the present ethical framework will be
      able to adequately answer arising questions. We think that many of the questions
      related to the consequences of pharmacogenomics are answerable along the lines of
      present ethical thinking. We also believe, however, that many 'changes of degree'
      may result in a 'change of kind.' We therefore think that pharmacogenomics may
      potentially have such a profound influence on scientific research and the
      pharmaceutical industry, the practice of medicine and society at large, that this
      will generate its own unique dynamic, which will require new ethical research. We
      suggest that the notion of 'responsibility' will be a major focus of such
      research.

PMID- 15449405
TI  - Tailored medicine: whom will it fit? The ethics of patient and disease
      stratification.
AB  - A key selling point of pharmacogenetics is the genetic stratification of either
      patients or diseases in order to target the prescribing of medicine. The hope is
      that genetically 'tailored' medicines will replace the current 'one-size-fits
      all' paradigm of drug development and usage. This paper is concerned with the
      relationship between difference and justice in the use of pharmacogenetics. This
      new technology, which facilitates the identification and use of difference, has,
      we shall argue, the potential to lead to injustice either by the inappropriate
      use of difference or through the inappropriate failure to use difference. We
      build on empirical data from a detailed study of the range of options for the
      development of pharmacogenetics to present a consideration of the ethical issues
      that surround patient and disease stratification. In it we explore the ways in
      which the use of pharmacogenetics may lead to the creation of new, genetically
      stratified, forms of difference and new forms of injustice based on these
      divisions. We also examine the ways in which existing forms of difference and
      social stratification may interact with the use of pharmacogenetics. In
      conclusion, we suggest how an understanding of these ethical issues could
      usefully inform future policy discussions.

PMID- 15449406
TI  - Pharmacogenetic testing, informed consent and the problem of secondary
      information.
AB  - Numerous benefits for patients have been predicted if prescribing decisions were
      routinely accompanied by pharmacogenetic testing. So far, little attention has
      been paid to the possibility that the routine application of this new technology
      could result in considerable harm to patients. This article emphasises that
      pharmacogenetic testing shares both the opportunities and the pitfalls with
      'conventional' disease-genetic testing. It demonstrates that performing
      pharmacogenetic tests as well as interpreting the results are extraordinarily
      complex issues requiring a high level of expertise. It further argues that
      pharmacogenetic testing can have a huge impact on clinical decisions and may
      influence the therapeutic strategy as well as the clinical monitoring of a
      patient. This view challenges the predominant paradigm that pharmacogenetic
      testing will predict patients' responses to medicines, but that it will not
      provide any other significant disease-specific predictive information about the
      patient or family members. The article also questions published proposals to
      reduce the consent procedure for pharmacogenetic testing to a simple statement
      that the physician wishes to test a sample of the patient's DNA to see if a drug
      will be safe or whether it will work, and presents an alternative model that is
      better suited to protect patient's interests and to obtain meaningful informed
      consent. The paper concludes by outlining conditions for the application of
      pharmacogenetic testing in clinical practice in a way that can make full use of
      its potential benefits while minimising possible harm to patients and their
      families.

PMID- 15449407
TI  - Ethical implications of pharmacogenetics--do slippery slope arguments matter?
AB  - Pharmacogenetics is a rapidly expanding area of research exploring the
      relationship between inter-individual genetic variation and drug response, with
      the goal of developing genetically optimised therapies. Slippery slope arguments
      claim that a particular action should be rejected (or supported) because it might
      be the first step onto a slippery slope leading to undesirable (or desirable)
      consequences. In this article, several slippery slope arguments relevant to the
      context of pharmacogenetics are evaluated under consideration of underlying
      reasons for their popularity. The author concludes that although the examined
      arguments are unconvincing as slippery slope arguments, they do matter in this
      context. While positive slippery slope arguments serve as a driving force to fuel
      the development of pharmacogenetics, their negative counterparts play an
      important role to sensitise policy makers and the public to potential problems.

PMID- 15449408
TI  - Untapped potential: IRB guidance for the ethical research use of stored
      biological materials.

PMID- 15449409
TI  - Research with victims of disaster: institutional review board considerations.

PMID- 15449410
TI  - Recruitment approaches for family studies: attitudes of index patients and their
      relatives.

PMID- 15449411
TI  - PVS versus the dying process.

PMID- 15449412
TI  - The landscape of dialogue.

PMID- 15449413
TI  - Gratitude and caution.

PMID- 15449414
TI  - The wisdom of tradition.

PMID- 15449415
TI  - A clear papal teaching.

PMID- 15449416
TI  - An end to the debate?

PMID- 15449417
TI  - The benefits-and-burdens ratio.

PMID- 15449419
TI  - Creating a glossary of terms, methods and instruments for clinical research in
      osteoarthritis: your help is needed.

PMID- 15449418
TI  - The dignity of the person.

PMID- 15449420
TI  - Distinct expression pattern of early- and late-response genes in normal and
      osteoarthritic human synovial membranes.
AB  - The significance of activating proteins (AP-1), c-fos, c-jun and jun B relative
      to the AP-1 responsive metallothionein, collagenase and stromelysin gene
      expression in the pathophysiology of osteoarthritis (OA) was investigated. The
      'early' c-fos, c-jun and jun-B mRNAs were ubiquitously expressed in normal and OA
      human knee synovial membranes. There was no strict correlation between expression
      of these and the AP-1 responsive, collagenase and stromelysin gene expression.
      Interestingly, the total metallothionein (MT) and the AP-1 responsive, MT-IIA
      gene-specific mRNAs were greatly diminished in OA compared with normal synovial
      membranes. The possible role of reduced expression of MT and trace metals in OA
      pathophysiology is discussed. Collectively, these data demonstrate a
      discoordinate expression of AP-1 encoding and their target genes in synovium.

PMID- 15449421
TI  - Proteoglycan depletion of intact articular cartilage by retinoic acid is
      irreversible and involves loss of hyaluronate.
AB  - Intact sesamoid bones from bovine metacarpophalangeal joints were cultured with
      retinoic acid for 9 days and allowed to recover in control medium for up to 17
      days. Retinoic acid (300 ng/ml) induced 91.8% inhibition of glycosaminoglycan
      (GAG) synthesis and 50.6% loss of sulfated GAGs from the cartilage. Retinoic acid
      also induced 38.2% loss of hyaluronate from the matrix. The synthesis and content
      of the large aggregating proteoglycan (aggrecan) were preferentially decreased
      compared with that of the small nonaggregating species. The aggrecan synthesized
      was similar to control aggrecan in size, aggregation capacity, and composition of
      its GAGs. GAG synthesis was almost completely restored in control medium within
      the next 6 days. The GAGs synthesized during recovery were slightly shorter than
      control GAGs and showed a higher ratio of chondroitin-6-sulfate over chondroitin
      4-sulfate. Neither the proteoglycan content nor the hyaluronate content recovered
      within 17 days. The aggregation capacity of newly synthesized aggrecan was
      normal. However, the retention of proteoglycans synthesized in the recovery
      period was much lower in treated cartilage than in control cartilage (T1/2 of 17
      and 38 days, respectively). In conclusion, the retinoic-acid-induced proteoglycan
      depletion was irreversible in spite of the restored synthesis of aggrecan with a
      normal aggregation capacity. The reduced retention of newly synthesized aggrecan
      during recovery might be caused by a lack of hyaluronate. This model seems
      suitable to study aspects of cartilage destruction and repair.

PMID- 15449422
TI  - Ridges and grooves on the bony surfaces of osteoarthritic joints.
AB  - Osteoarthritis (OA) is associated with disruption of the articular cartilage and
      remodeling of subchondral bone. However, the macroscopic changes seen on the
      surface of the underlying bone have received little attention. Deep parallel
      ridges and grooves of the subchondral, eburnated bone have been observed in
      palaeopathological skeletons with OA. The same phenomenon has been seen in
      contemporary bones treated to remove soft tissues. Four such specimens were
      examined in detail and the characteristics of the ridges were documented by
      reflex microscopy. The depth and peak-to-peak distance of the grooves varied
      considerably. In each case there was matching of ridges and grooves on the two
      articulating surfaces of the joint, which fitted together like cog-wheels. This
      previously undocumented aspect of the pathology of OA may have significance to
      the function and outcome of an osteoarthritic joint, raises questions on the
      nature and control of subchrondal bone changes in OA.

PMID- 15449423
TI  - Induction of osteoarthritis by intra-articular injection of collagenase in mice.
      Strain and sex related differences.
AB  - To study the effects of strain and sex on the development of injury-induced
      osteoarthritis (OA) in murine knee joints, two doses of highly purified bacterial
      collagenase (10 units and 30 units) were injected into male and female mice of
      two closely related strains, C57BL6 and C57BL10. Frontal histological sections of
      whole knee joints were made late in the disease process and examined for
      osteoarthritic lesions. Differences in prevalence of cartilage damage between
      strains and sexes were observed. Prevalence was higher in C57BL10 (male: almost
      100%) than in C57BL6 (male: about 25%), and the prevalence was twice as high in
      males as in females in both strains. The amount of collagenase (10 or 30 units)
      did not affect the prevalence of lesions, however, it did influence the severity
      of the damage. The site of the damage appeared to be dose and strain dependent.
      Male C57BL6 always showed damage on the medial tibial plateau, independent of
      dose. In male C57BL10 damage almost always appeared on the lateral tibial plateau
      with 10 units, while with 30 units the medial plateau also became strongly
      involved. Since it is known that male mice are more prone to spontaneous OA than
      female mice and C57BL10 are more prone han C57BL6 mice, it can be concluded that
      predisposition to spontaneous osteoarthritis increases the risk of developing
      injury-induced osteoarthritis. Location and severity of the changes will probably
      be related to joint loading.

PMID- 15449424
TI  - The epidermal growth factor-like domain of the large proteoglycans from articular
      cartilage (aggrecans). Estimate of content at different ages and in
      osteoarthritis.
AB  - Sequencing of cDNA clones has shown that the carboxy terminal domain of the core
      protein of large proteoglycans (aggrecans) from human cartilage contains an
      epidermal growth factor-like (EGF-like) domain which is alternatively spliced. In
      a previous study it was found that the domain of the translated protein can be
      recognized by polyclonal antibodies to mouse EGF. A competitive enzyme-linked
      immunoabsorbent (ELISA) assay has been developed to evaluate the EGF-like domain
      content of aggrecans at various ages and in osteoarthritis. Fetal aggrecans
      digested with protease free chondroitinase ABC were adsorbed on polyvinyl
      chloride microtiter plates followed by blocking with bovine serum albumin and
      goat serum. Mixtures of known amounts of protein of digested aggrecans and
      constant amounts of anti-mouse EGF antibodies were incubated and added to plates.
      The second antibody was peroxidase-conjugate F(ab')2. Fetal, newborn and child
      aggrecan proteins have a higher content of EGF-like domain than aggrecan proteins
      from cartilage of older humans. Three areas of cartilages from osteoarthritic
      joints were separated: cartilages with normal macroscopic appearance, erosion
      border cartilage and osteophytic cartilage. Values derived from these samples
      were compared with values derived from nonosteoarthritic aged humans. The content
      of aggrecans from osteoarthritic cartilage with normal macroscopic appearance was
      similar to or slightly lower than the latter. The aggrecans from osteophytes had
      a higher EGF-like domain content. The aggrecans from the erosion border had a
      variable content, close to noneroded cartilages, to osteophytes or in between the
      values obtained for noneroded cartilages and for osteophytes. Variations in the
      amount of newly synthesized aggrecans, in the proteolysis of the carboxy terminal
      domain of aggrecans and in the alternating splicing of the EGF-like domain might
      explain the results shown here.

PMID- 15449425
TI  - Elevation in urinary levels of pyridinium cross-links of collagen following
      chymopapain-induced degradation of articular cartilage in the rabbit knee
      provides evidence of metabolic changes in bone.
AB  - To measure urinary levels of two pyridinium cross-links of collagens at various
      times, rabbits were injected in the left knee with 0.2 mg (N = 11) or 2.0 mg
      chymopapain (N = 11). Urinary levels of the bone-specific deoxy-pyridinoline
      cross-link and of the hydroxylysyl pyridinoline cross-link, found in large
      amounts in articular cartilage and bone, were measured by high performance liquid
      chromatography (HPLC). The urinary levels were correlated with histological
      evidence of progressive articular cartilage destruction in animals injected with
      2.0 mg chymopapain and of successful repair in rabbits injected with the lower
      dose. Rabbits injected with 2.0 mg chymopapain showed a very large increase in
      urinary levels of deoxy-pyridinoline during the first 30 days after the
      injection. This rise was not seen in animals injected with the lower dose. A rise
      in urinary level of the hydroxylysyl pyridonline cross-link was observed in all
      rabbits but was more pronounced and lasted longer in animals receiving the higher
      dose. The failure of rabbits injected with 2.0 mg chymopapain to repair the
      damaged articular cartilage was strongly associated with a marked increase in the
      catabolism of the bone-specific deoxy-pyridinoline cross-link and to a lesser
      extent with the catabolism of the hydroxylysyl pyridinoline found in bone and in
      articular cartilage.

PMID- 15449426
TI  - Metabolic and structural changes in newly synthesized proteoglycans induced by
      implantation of a polyethylene sheet in the rabbit knee joint.
AB  - A sheet of polyethylene was surgically implanted in a rabbit right patello
      femoral joint and changes in the structure and chemical composition of newly
      synthesized articular cartilage proteoglycans (PGs) were studied 1 month after
      surgery. The articular cartilage from implanted and sham-operated control knee
      joints was labeled in vitro with 3H-glycine and 35S-SO4 and then extracted with 4
      M guanidinium chloride (GuHCl) solution. Labeled extracts were analyzed by
      dissociative CsCl gradient centrifugation and by Sepharose CL-2B column
      chromatography. The labeled glycosaminoglycan side chains were analyzed by
      Sephadex G-200 column chromatography and specific enzymatic digestions. Compared
      with sham-operation, the trochlear articular cartilage of operated joints
      incorporated more 35S-SO4 and 3H-glycine into newly synthesized PGs and proteins.
      It also synthesized a higher proportion of extractable, hydrodynamically large
      and high density 35S-PG monomers with increased proportion of molecules, able to
      interact with exogeneous hyaluronan (HA). The fibro-cartilagenous 'osteo
      chondrophytic' spurs, compared with trochlear hyaline articular cartilages,
      incorporated less 35S-SO4 and 3H-glycine and synthesized less extractable high
      density 35S-PG monomers able to interact with exogenous HA. Their 35S-GAG side
      chains were more heterogeneous and segregated into three distinct peaks as shown
      by Sephadex G-200 column chromatography. The results of the present studies
      demonstrate that, in response to the implant, there was an increase in the
      biosynthetic capacity of chondrocytes which synthetized larger PG monomers able
      to interact wih HA.

PMID- 15449427
TI  - It's time to fix broken insurance promises to workers.

PMID- 15449428
TI  - Costs, commitment and locality: a comparison of for-profit and not-for-profit
      health plans.
AB  - Following on the heels of the first national study demonstrating differences in
      the community benefits provided by not-for-profit and for-profit health
      maintenance organizations (HMOs) (Schlesinger, Mitchell, and Gray 2003), this
      study of the New York state market shows significant differences in premiums,
      administrative overhead and commitment to safety net coverage between nonprofit
      and for-profit health plans. This study shows that for-profit health plans do act
      differently than not-for-profit plans in terms of performance, efficiency, and
      contribution to safety net programs. Moreover, it suggests that not-for-profit
      health insurers operating in a predominantly for-profit market act in many ways
      like for-profits. The New York state insurance market provides an ideal study
      environment because one can compare a large number of policyholders and plans in
      both business models (for-profit and not-for-profit) that share an identical
      legislative and regulatory environment. New York has large populations being
      provided coverage under both models and no allowances had to be made for state-to
      state political and/or legal differences. Specifically, this study shows that:
      The downstate insurance market is predominantly for-profit, while the upstate
      market is almost entirely not-for-profit. The recent conversion of Empire Blue
      Cross Blue Shield to a for-profit model moves the downstate market further into
      the for-profit column, while the upstate region remains not-for-profit. Insurers
      in the upstate not-for-profit market are more administratively efficient than
      insurers in the downstate region. Compared to the downstate region, insurers in
      upstate New York spent 1.5% less of their operating revenues on administrative
      expenses. The additional 1.5% of spending on administrative expenses downstate
      totals dollars 137,000,000. Upstate insurers spend significantly more of the
      revenues received on payments for medical care. Downstate insurers spent 80.4% of
      operating revenues on medical care. Upstate insurers spent 87.7% of operating
      revenue on medical care. If health care spending patterns downstate were similar
      to upstate, the additional 7.3% allocated to medical care would total dollars
      678,000,000. A lower level of investment in medical care in the downstate region
      translated into higher underwriting gains, which totaled 8.1% of operating
      revenue. Plans in the upstate region reported underwriting gains of only 2.3%.
      Not-for-profit insurers offer more cost effective (i.e., lower) premium options
      for consumers. In 2002, the upstate market had the lowest operating revenues
      (premiums) statewide, averaging dollars 184 per member per month (pmpm); the not
      for-profit plans downstate averaged dollars 203 pmpm. Premiums in the for-profit
      segment of the downstate market averaged dollars 221 pmpm in 2002. The not-for
      profit upstate market has proved its viability, while maintaining commitments to
      New York safety net and Medicare programs. The not-for-profit upstate market
      experienced a dollars 12 million loss in New York safety net programs in 2002,
      but generated dollars 131 million in underwriting gains for all product lines
      combined. Furthermore, upstate revenue gains in 2002 exceeded 2001 results by
      dollars 45 million. Not-for-profit HMOs, both upstate and downstate, participate
      in state-sponsored safety net programs to a far greater degree than the downstate
      for-profit managed care organizations. Within the plan group selected for this
      study, the not-for-profit plans supported 88% of the enrollment in New York state
      sponsored programs, compared with for-profit plans' support of only 12% of safety
      net membership. Not-for-profit plans have also demonstrated a higher level of
      dedication to the Medicare Plus Choice product line than for-profit insurers
      downstate. In 2002, not-for-profit plans enrolled 73% of this population of
      385,000 elderly statewide. Despite the favorable financial returns in the product
      line, for-profit insurers downstate enrolled only 105,000 Medicare risk members
      in 2002, or 27% of the statewide total. The emergence in New York of health care
      insurance markets that are predominantly for-profit raises significant public
      policy issues, especially with reference to community benefits and services.
      Should the upstate health insurance environment change with the entrance of for
      profit plans or conversion of existing plans to for-profit status, the upstate
      market is likely to look very similar to the downstate in that there will be
      diminished access to care for the at-risk population; premium costs will be
      higher and administrative costs will be higher. The health care insurance market
      upstate would become less attentive to the provision of public goods as insurers
      strive to maximize their economic advantages.

PMID- 15449429
TI  - Government as reinsurer: potential impacts on public and private spending.
AB  - This paper analyzes the potential effects of alternative government reinsurance
      mechanisms on public and private expenditures in group and nongroup health
      insurance markets. High reinsurance thresholds, with the government taking
      responsibility for costs over dollars 50,000 per year, would absorb a small share
      of private costs. Lower thresholds would have greater effects, but would increase
      government costs significantly. We also find that reinsurance would reduce the
      variance in expenditures considerably and should reduce risk premiums charged by
      private insurers. We conclude that focusing on small employers and the nongroup
      market could target government spending where costs are highest and insurance
      markets most unstable.

PMID- 15449430
TI  - The effect of managed care market share on appropriate use of coronary
      angiography among traditional Medicare beneficiaries.
AB  - Evidence suggests that when managed care market share increases in a geographic
      area, expenditures in Medicare's fee-for-service sector decrease. But it is
      unclear how expenditure reductions relate to the quality of medical care for
      traditional Medicare beneficiaries. We estimated how managed care market share
      varied with the proportion of fee-for-service Medicare beneficiaries who were
      admitted for acute myocardial infarction (AMI) and underwent angiography. We
      classified patients as appropriate, discretionary, and inappropriate, according
      to guidelines of the American College of Cardiology and the American Heart
      Association (ACC-AHA). Within all ACC-AHA classes, coronary angiography fell
      slightly as managed care market share increased.

PMID- 15449431
TI  - Managed care discounting: evidence from the MarketScan database.
AB  - The paper examines price discounting by health maintenance organizations (HMOs)
      and preferred provider organizations (PPOs) in markets for hospital services. Our
      empirical analysis focuses on transaction prices for angioplasty, which is a
      relatively common procedure with well-defined "product" characteristics. After
      controlling for patient and procedure heterogeneity and market power, we find
      that on average angioplasty prices are 8% lower for PPOs than for fee-for-service
      plans, followed by point-of-service HMOs, which capture a 24% discount. Our
      results are in general agreement with earlier work by Cutler, McClellan, and
      Newhouse (2000), who show that managed care discounts are "real," after
      accounting for case severity and process of care.

PMID- 15449432
TI  - Malpractice experience and the incidence of cesarean delivery: a physician-level
      longitudinal analysis.
AB  - This study examines the influence of malpractice claims on the practice behavior
      of a panel of obstetricians in Florida during the period 1992-1995 to determine
      whether physicians respond to malpractice events by performing more cesareans,
      consistent with the notion that cesarean sections are employed as "defensive
      medicine." Findings indicate that clinical events resulting in claims that lead
      to substantial indemnity payments have a significant, modest effect on physician
      practice behavior: physicians experiencing those claims increase their risk
      adjusted cesarean rates by about one percentage point. Malpractice experience
      does not appear to affect patient mix, but claims with large payouts may affect
      patient volume.

PMID- 15449433
TI  - Smoke without fire: nursing facility closures in California, 1997-2001.
AB  - This paper draws from a rich longitudinal California data set to analyze the
      scope and nature of nursing home closures between 1997 and 2001, and to present a
      Cox proportionate hazards model of the risks of closure that arise from a range
      of facility and market characteristics. When compared with the sample total of
      1,482 facilities operating in the baseline year of 1997, only 56 facilities
      closed through 2001, involving the loss of 3.8% of facilities and 2,915 beds
      (2.3%). The multivariate Cox model of factors associated with closure reports
      that: 1) hospital-based facilities are 600% more likely to close than are free
      standing homes; 2) reducing bed size by one standard deviation (52 beds)
      increases the risk of closure by 460%; 3) facilities with losses of 5% or worse
      are more than twice as likely to close; and 4) a one-standard deviation increase
      in the spare bed capacity measure of county competition raises the risk of
      facility closure by 140%.

PMID- 15449434
TI  - Assessing risk-adjustment approaches under non-random selection.
AB  - Various approaches have been proposed to adjust for differences in enrollee risk
      in health plans. Because risk-selection strategies may have different effects on
      enrollment, we simulated three types of selection--dumping, skimming, and
      stinting. Concurrent diagnosis-based risk adjustment, and a hybrid using
      concurrent adjustment for about 8% of the cases and prospective adjustment for
      the rest, perform markedly better than prospective or demographic adjustments,
      both in terms of R2 and the extent to which plans experience unwarranted gains or
      losses. The simulation approach offers a valuable tool for analysts in assessing
      various risk-adjustment strategies under different selection situations.

PMID- 15449435
TI  - Comparing accuracy of risk-adjustment methodologies used in economic profiling of
      physicians.
AB  - This paper examines the relative accuracy of risk-adjustment methodologies used
      to profile primary care physician practice efficiency. Claims and membership data
      from an independent practice association health maintenance organization (HMO)
      were processed through risk-adjustment software of six different profiling
      methodologies. The Group R2 statistic was used to measure, for simulated panels
      of HMO members, how closely each methodology's cost predictions matched the
      panel's actual costs. All but one methodology explained at least 50% of panel
      cost variance with panels as small as 25 patients. Group R2 performance tended to
      be better when high-cost cases were included rather than excluded from the
      analyses.

PMID- 15449436
TI  - Drastic changes imminent at Health Professions Council (Hpcsa).

PMID- 15449437
TI  - A national survey of oral hygienists in South Africa.
AB  - AIM: To survey the status and views of practicing hygienists in South Africa.
      METHOD: A postal questionnaire was mailed to all registered hygienists in South
      Africa in 1999 (n = 853). Demographic variables; views on further study;
      conditions of employment; and issues hygienists' felt strongly about were
      explored. Two mailings resulted in a response rate of 51% (n = 439). RESULTS:
      Respondents' age ranged from 20-52 years (mean 33 years); they were all female (n
      = 435) except two; 60.9% were in full time and 39.1% part time employment; 73%
      were employed in private practice, 13% in non-traditional settings and a small
      number in commerce; 92.7% wished to expand on their current qualification with
      part time and distance learning as the choice of study; 45.7% of the full time
      and 18% of the part time hygienists reported to have a contract of employment.
      CONCLUSION: The results of this study show that South African hygienists envision
      an expanded role within the oral health team and wish to pursue their career
      beyond the two-year diploma in Oral Health/Oral Hygiene. The majority were not
      employed according to the BCEA in terms of benefits and the provision of a
      contract if employment.

PMID- 15449438
TI  - Flexural properties of denture-base polymer reinforced with glass-fibre
      polysulphone composite.
AB  - The aim of this study was to determine the effect of glass-fibre composite
      reinforcement on the flexural strength and flexural modulus poly-methyl
      methacrylate (PMMA). Prefabricated electrical glass-fibre polysulphone composite
      rods (GF/PSu), 3mm in diameter, were incorporated in cylindrical, heat
      polymerizing PMMA specimens with diameters of 4, 5 and 6mm respectively (n = 10).
      These specimens were compared with PMMA control groups of similar dimension. A
      three point loading test was performed in air after storage of specimens in water
      at 37 degrees C for 8 weeks. The following variables were measured : Flexural
      Strength (FS) and Flexural Modulus (FM). The data were analyzed using one way
      analysis of variance (ANOVA). After testing, the fracture zone was evaluated
      using a scanning electron microscope (SEM). The glass-fibre reinforcement used in
      this study significantly enhanced both the FM and FS values of PMMA. This
      enhancement was, however, progressively reduced in relation to an increase in
      cross-sectional dimension of the specimens. SEM evaluation revealed delamination
      and fracture of the glass-fibres in the polymer matrix.

PMID- 15449439
TI  - Infection control in dentistry.

PMID- 15449440
TI  - Reappraising prosthodontic treatment goals for older, partially dentate people:
      Part I. Traditional management strategy.
AB  - In conventional terms, prosthodontic treatment becomes necessary when a patient
      has missing and/or broken-down teeth. Part I of this two-part series of papers
      reviews the available evidence for a traditional therapeutic model that seeks
      purposefully to reconstitute lost morphology, with specific reference to older,
      partially dentate people, at the population level. Furthermore, because anterior
      and premolar teeth are indispensable to a number of prime oral functions in most
      societies, the question of need for replacement relates essentially to that of
      molar teeth. Research findings are presented which cast doubt on many of the
      assertions made for the mandatory replacement of all posterior teeth.
      Specifically, there appears to be a lack of compelling evidence that dental arch
      integrity is a prerequisite for optimal oral health and function, and favours the
      prognosis of the remaining dentition. Wide variability in the effects of
      posterior tooth loss on occlusal stability indicates a 'wait-and-see' management
      approach rather than immediate replacement, while reported chewing sufficiency in
      people with reduced but well-distributed dentitions, and a lack of association
      between the level of posterior support and temporomandibular disorders, further
      undermine the traditional premise for the mandatory replacement of posterior
      teeth, specifically molars. With the parallel recognition that the assessment of
      treatment need must take a broader view of peoples' functional concerns arising
      from their tooth loss, as well as weighing the cost/benefit ratio of treatment,
      Part II will compare the merits of the traditional model with the documented
      functional benefits that a more limited, less morphologically-driven approach may
      have for the growing, older sector of society.

PMID- 15449441
TI  - Preventative dentistry: essential oils and oral malodour.

PMID- 15449442
TI  - New concepts in treatment of sepsis.
AB  - Critically ill patients still commonly die of the effects of sepsis, despite
      numerous interventions. Earlier trials investigated mostly anti-inflammatory
      strategies, based on the prevailing theory that sepsis represents an uncontrolled
      inflammatory response. We now know that sepsis represents a biphasic response to
      infection, and the initial pro-inflammatory response that we have targeted thus
      far is invariably followed by a prolonged period of immune suppression. Indeed, a
      patient may oscillate between a pro- and anti-inflammatory state repeatedly. The
      use of steroids remains controversial, and should probably be reserved for a
      select subset of patients. The coagulation cascade has a powerful effect on
      inflammation, and manipulation by means of Activated Protein C has been
      beneficial. It appears tremendously advantageous to resuscitate the critically
      ill patient early and aggressively to maintain normal oxidative metabolism. This,
      coupled with the rigorous maintenance of a physiologically neutral milieu
      (particularly blood glucose levels) seems to be the most powerful weapon we have
      to manage the critically ill patient with sepsis.

PMID- 15449443
TI  - General practitioner's radiology case 22. Rheumatoid arthritis.

PMID- 15449444
TI  - [Morphometric and histological evaluation of uterine leiomyomas treated with GnRH
      agonists or progestational agents].
AB  - Both gonadotropin-releasing hormone (GnRH agonists) and progestational agents are
      commonly used in order to reduce the size of uterine leiomyomas before surgery.
      So far, little is known about the histologic changes underlying such shrinkage
      mechanism. Probably the conflicting data on this subject are due to the
      qualitative and subjective methods used by most previous reports. In this study
      we analyzed 42 leiomyomas from patients treated with GnRH agonists (14 different
      patient samples), patients treated with progestational agents (14 different
      patient samples) and age-matched control patients (14 different patient samples),
      using qualitative (light microscope analysis) and quantitative (morphometric
      analysis by a specific software) methods. We assessed the following parameters:
      areas of necrosis, areas of hyalinization, vasal density, vasal thrombi,
      thickness of vasal walls, size of vasal lumina, cell density, maximum nuclear
      diameter, maximum cytoplasmic diameter, mitotic index on each sample. The
      analysis showed that leiomyomas from women treated with GnRH agonist exhibited
      broader areas of necrosis, greater cell density, and wider vasal lumina, while
      those from women treated with progestational agents exhibited thicker vasal walls
      than the other two groups, respectively. In conclusion, our results suggest that
      vasal wall changes are the basis of leiomyomas shrinkage after GnRH agonist
      therapy.

PMID- 15449445
TI  - ["Ancillary" methods, marketing, and health care models. To be precise: between
      ethics and marketing, an investigation of quality or of profit?].

PMID- 15449446
TI  - [Primary squamous cell carcinoma of the breast: a case report].
AB  - INTRODUCTION: Primary squamous cell carcinoma (SCC) of the breast is an extremely
      rare entity and it has a low incidence in comparison with all other mammary
      cancers. MATERIAL AND METHODS: We describe a case of SCC of the breast in a 55
      year old woman who presented with a painless mass located in the external
      quadrant of the left breast. The neoformation, once removed, was tamponate
      formalin fixed and routinely processed for inclusion in paraffin. Sections were
      stained with haematoxilin-eosin and immunohistochemical and electron microscopy
      investigations were performed. RESULTS: Histologically, the neoplasia was
      characterized by cystic cavities covered by nests and sheaths of poorly
      differentiated squamous cells with keratinized areas. Mitotic activity was high,
      as well as cellular proliferative index, evaluated by Mib-1 (ki 67) antibody. At
      immunohistochemistry, the tumor cells were diffusely positive for high molecular
      weight cytokeratins and c-erbB-2, negative for vimentin, estrogen and
      progesterone. CD68 and LCA were positive only in the inflammatory cells. Electron
      microscopy confirmed the epithelial nature of the neoplastic cells. A diagnosis
      of SCC of the breast was made, and a radical mastectomy was performed.
      CONCLUSIONS: We make a brief review of the literature and discuss the main
      histologic criteria for the differential diagnosis with adenocarcinoma of the
      breast with squamous metaplasia.

PMID- 15449447
TI  - [Retroperitoneal Pacinian neuroma: report of a rare lesion in an uncommon
      location].
AB  - Pacinian neuroma is an extremely rare benign tumor which has only occasionally
      been reported in the literature. To date, this lesion has usually been observed
      in the hand and foot; only one had intra-abdominal localization. Local trauma is
      reported in the most of these cases. We describe the first case of
      retroperitoneal pacinian neuroma. The lesion was observed as an incidental
      finding in a 75-year-old man who underwent laparotomy for aortic aneurysm. Here
      are discussed the differential diagnosis and a complete literature review on the
      topic.

PMID- 15449448
TI  - [Tumoral, quasitumoral and pseudotumoral lesions of the superficial and somatic
      soft tissue: new entities and new variants of old entities recorded during the
      last 25 years. Part II: The list and a review].

PMID- 15449449
TI  - [Remembrance of Professor Raffaele Lattes].

PMID- 15449450
TI  - Bovender, Fetter focus on uninsured before Congress.

PMID- 15449451
TI  - Federation urges lower outlier threshold; opposes hospital-within-hospital
      admission limits.

PMID- 15449452
TI  - CMS solicits comments for proposal to fund undocumented aliens' care.

PMID- 15449453
TI  - Bush Administration, Capitol Hill unveil IT initiatives.

PMID- 15449454
TI  - Protecting Medicaid today and tomorrow.

PMID- 15449455
TI  - On pricing, think wholesale.

PMID- 15449456
TI  - Kuru: a half-opened window onto the landscape of neurodegenerative diseases.
AB  - Kuru, the first human neurodegenerative disease classified as a transmissible
      spongiform encephalopathy (TSE), prion disease or, in the past, as a slow
      unconventional virus disease, was first reported to Western medicine in 1957 by
      Gajdusek and Zigas. A complete bibliography of kuru through 1975 has been
      published by Alpers et al. The solution of the kuru riddle opened a novel field
      of biomedical sciences and initiated more than a quarter of century of research
      that has already resulted in two Nobel prizes (to D. Carleton Gajdusek in 1976
      and to Stanley B. Prusiner in 1997) and was linked to a third (to Kurt Wuthrich
      who determined the structure of the prion protein). Kuru research has impacted
      the concepts of nucleation-polymerization "protein cancers", and "conformational
      disorders". This paper is dedicated to Dr. Carleton Gajdusek on the occasion of
      his 80th birthday. "Kuru" in the Fore (Fig. 1) language means to shiver from
      fever or cold. The Fore used the noun of the kuru-verb to describe the always
      fatal disease which decimated their children and adult women but rarely men. It
      has been and still is restricted to natives of the Fore linguistic group at Papua
      New Guinea's Eastern Highlands and those neighboring linguistic groups which
      exchange women with Fore people (Auiana, Awa, Usurufa, Kanite, Keiagana, late,
      Kamano, Kimi; Fig. 2). Neighboring groups into which kuru-affected people did not
      settle through marriage or adoption, such as the Anga (Kukukuku), and remote
      lagaria, Kamano and Auiana people, were not affected. It seems that Kuru first
      appeared at or shortly after the turn of XX century in Uwami village of Keiagana
      people and spread to the Awande in the North Fore where the Uwami had social
      contacts. Within 20 years it had spread further into the Kasokana (in 1922
      according to Lindebaum) and Miarasa villages of North Fore, and a decade later
      had reached the South Fore at the Wanikanto and Kamira villages. Kuru became
      endemic in all villages that it entered and became hyperendemic in the South Fore
      region. All native informants stressed the relatively recent origin of kuru.
      Interestingly enough, when kuru first appeared, it was considered poetically by
      Fore as similar to "the swaying of casuarinas tree" and kuru was labeled
      cassowary disease to stress the similarity between cassowary quills and "waving
      casuarinas fronds". Gajdusek first learned about kuru from Dr. Roy Scragg,
      director of Public Health in Port Mosby, who had already read a report sent by
      Dr. Vin Zigas to Dr. John Gunter in 1956. In March 1957, Gajdusek joined Zigas,
      who at that time was a medical patrol officer in Kainantu, Eastern Highland
      District of the Territory of Papua New Guinea.

PMID- 15449457
TI  - Prion diseases: from transmission experiments to structural biology--still
      searching for the cause.

PMID- 15449458
TI  - Molecular approaches to mechanisms of prion diseases.
AB  - Prion diseases such as scrapie in sheep, bovine spongiform encephalopathy in
      cattle, Creutzfeldt-Jakob disease, Gerstmann-Straussler-Scheinker disease and
      fatal familial insomnia in man are neurodegenerative disorders. In humans, the
      diseases can be sporadic, inherited, or acquired by infection. The underlying
      pathogenic event in prion diseases is a conformational modification of the
      cellular isoform prion protein (PrP(C)) to the pathogenic isoform (PrP(SC)) that
      accumulates in the central nervous system. However, in humans, in some inherited
      cases the pathological PrP is not PrP(Sc), but a transmembrane form of prion
      protein, (Ctm)PrP. Prion protein is encoded by the cellular gene, PRNP, which has
      been mapped to human chromosome 20p21. Familial prion diseases are thought to
      result from a change in structure of the prion protein produced by the mutated
      PRNP gene. Furthermore, polymorphic codon 129 of the PRNP gene encodes either
      methionine or valine and appears to influence the susceptibility of patients to
      iatrogenic and sporadic CJD as well as the neuropathological phenotype in these
      forms of CJD. Polymorphisms in the promoter region of PRNP gene or disturbances
      in prion protein metabolism, such as incorrect activity of cellular chaperones or
      proteasomes are considered as susceptibility factors in human prion diseases.

PMID- 15449459
TI  - Doppel: the prion's double.
AB  - Doppel (Dpl) is a PrP-like protein, coded by a gene named PRND, located near the
      PRNP (prion proten coding gene) locus. Human Dpl is a 179-amino acid protein
      showing approximately 25% sequence identity with the carboxyproximal two thirds
      of the human cellular prion protein (PrPC). A comparison of the structures of Dpl
      and PrP(C) reveals similarities in the secondary structure and topology. Apart
      from their structural similarities, the PrP and Dpl proteins seem to have
      different functions. The Prnd gene is expressed in mouse embryos; in adult mice
      its transcripts are present in heart, mammary gland, spleen, testes and, in
      contrast to Prnp, only at very low levels in the adult CNS. Moreover, the Dpl
      protein is not capable of enhancing the propagation of the pathological prion
      protein (PrP(Sc)). The Dpl protein has been identified as a regulator of acrosome
      function and male gametogenesis. The human PRND open reading frame has been shown
      to contain polymorphic codons, but research on a correlation between the PRND
      polymorphic sequences and neurodegenerative disorders carried out to date in
      different populations have shown contradictory results. Therefore, the role of
      the PRND gene in CJD and other diseases still remains unexplained.

PMID- 15449460
TI  - Bovine spongiform encephalopathy (BSE): the end of the beginning or the beginning
      of the end?
AB  - Bovine spongiform encephalopathy (BSE) is a zoonosis being the origin of variant
      Creutzfeldt-Jakob disease and an important cattle disease in its own right. This
      association has driven both the research into the disease and extensive
      epidemiological investigations of practical value. Not only has the occurrence of
      BSE has a serious effect on animal health and public health, it has also
      seriously interrupted trade in cattle and cattle products from affected
      countries. Since 2001, several additional European countries, Japan, Israel and
      Canada have reported BSE in native-born stock and this has led to a concern about
      the BSE status of countries that have imported cattle and cattle products from
      any affected country. A single case recently reported in the USA was in a cow
      imported from Canada, thus extending the risk of BSE occurrence into the North
      American continent as a whole. Extensive feed and offal bans have protected the
      food and feed chains in all countries with BSE, even though initially they tended
      to be leaky. Application of newly-developed, approved 'Rapid' tests for misfolded
      PrP in central nervous tissue of targeted, high-risk animals and slaughter cattle
      now provides the tools whereby the real incidence of the disease (and to a
      degree, infection) can be determined in an active surveillance programme. 'Rapid'
      testing also enables the progress of epidemics to be monitored in response to
      applied measures. In the EU, over 10 million cattle are tested annually. Analysis
      of the extensive data shows that it is the beginning of the end of the BSE
      epidemic in the UK; most European countries, Israel and Japan are close behind.
      The epidemic in North America (two cases to date) is at the beginning.
      Significant measures had already been adopted there to reduce the risk from
      recycling of infection via feed but it remains to be seen if they are watertight.
      Advice has been given to ensure that public health is protected and to monitor
      the epidemic by strategic use of approved 'Rapid' tests to determine that the
      epidemic is in fact trivial as believed, or otherwise to identify weaknesses in
      measures that can be corrected. It is imperative that all countries conduct risk
      assessments for BSE, follow the OIE recommendations and do not unreasonably
      disrupt international trade. There is a responsibility for all countries with BSE
      to ensure that infection is not exported to any country, particularly through
      live cattle and especially via meat-and-bone-meal, which is the acknowledged
      vehicle of transmission. There is also a responsibility placed upon all countries
      to protect, not only their cattle populations, but also their human populations
      from exposure to this economically important fatal disease. If all the advice is
      taken and measures enforced there is a prospect that BSE can be eliminated from
      countries and regions as a prelude to eradication from the world.

PMID- 15449461
TI  - Contribution of neuropathology to the understanding of human prion disease.
AB  - Neuropathology is an important tool for definitive diagnosis of sporadic,
      genetic, and acquired prion disease. Classical neuropathological hallmark is the
      highly disease-specific spongiform change accompanied by neuronal loss, astro-
      and microgliosis. Spongiform change of the neuropil consists of either
      microcystic or confluent vacuoles and varies greatly within the same brain. In
      addition, the most important aspect of confirmatory diagnosis is the
      demonstration of disease-associated prion protein (PrP(d)) by
      immunohistochemistry or Western blotting. Different PrP(d) immunostaining
      patterns include patchy/perivacuolar surrounding spongiform change,
      diffuse/synaptic, perineuronal, or plaque type. The latter includes unicentric
      kuru-type plaques or multicentric plaques as in the peculiar genetic prion
      disorder, Gerstmann-Straussler-Scheinker disease. PrP(d) immunostaining patterns
      correlate well with phenotypes defined by the polymorphic codon 129 and the type
      of protease resistant PrP(d) seen on Western blots. PrP(d) immunoreactivity in
      the cerebellum may be highly informative about disease subtypes. Although the
      central nervous system is the major site of PrP(d) accumulation, it may also be
      observed in peripheral nerves as adaxonal deposits; in skeletal muscle as
      granular immunoreactivity in particular in abundance in a unique instance of
      concomitant Creutzfeldt-Jakob disease and inclusion body myositis; as well as
      associated with dendritic cells and macrophages in vessel walls. A subset of
      inhibitory GABAergic neurons is selectively affected in experimental and human
      prion disease. The central pathogenetic cascade includes oxidative stress and
      apoptosis. Deposition of terminal complement components on neurons accompanies
      tissue damage.

PMID- 15449462
TI  - Variant Creutzfeldt-Jakob disease.
AB  - Current evidence indicates that variant Creutzfeldt-Jakob disease is caused by
      the transmission of bovine spongiform encephalopathy to humans. The clinical and
      investigative features of variant CJD are relatively distinct from sporadic CJD
      and the neuropathological appearances are novel. The number of cases of vCJD in
      the UK may have peaked, but the total future number of cases of vCJD is uncertain
      and the possibility of secondary iatrogenic transmission via blood transfusion
      has recently been identified.

PMID- 15449463
TI  - Review: pathology of variant Creutzfeldt-Jakob disease.
AB  - Variant Creutzfeldt-Jakob disease (vCJD) is a novel human prion disease that
      results from exposure to the bovine spongiform encephalopathy (BSE) agent,
      probably by the oral route. The pathological features of vCJD are unique, with
      extensive involvement of lymphoid tissues in addition to the central nervous
      system. This article reviews the histopathology and biochemistry of vCJD,
      emphasising diagnostic features and indicating several areas of active research.
      The widespread distribution of infectivity in lymphoid tissues in vCJD has lead
      to concerns over the possibility of iatrogenic disease transmission by
      contaminate surgical instruments, or by blood transfusion. vCJD has so far only
      occurred in individuals within a genetic subset defined by the natural
      polymorphism at codon 129 in the prion protein gene. It remains uncertain if this
      disease will occur in other genetic subgroups within the population. Continuing
      surveillance of vCJD in the UK and other countries in which BSE has been
      identified will be necessary for future estimations of disease numbers worldwide.

PMID- 15449464
TI  - Schlieren systems with coherent illumination for quantitative measurements.
AB  - Schlieren systems with a coherent light source were investigated by the Fourier
      optics technique. The imaging properties of the systems with various cutoff
      filters were studied. Systems with a graded piecewise linear filter and a
      Gaussian step function convolution (graded) filter are considered, demonstrating
      that the image can be approximated by the geometrical-optics theory of
      conventional schlieren systems. A nonlinear phase contribution was estimated,
      allowing for the measurement of strong phase objects. Within the framework of
      linear approximation the results are described by the phase derivative point
      spread function, introduced in this paper as the schlieren point-spread function.
      In addition, modification of the Lopez cutoff filter is proposed, demonstrating
      its superiority over the piecewise linear and the Gaussian step convolution
      filters. Simulations of coherent schlieren imaging as well as phase derivative
      measurements were performed. Finally, the imaging properties of the schlieren
      systems with the different filters are compared.

PMID- 15449465
TI  - Refractometry of microscopic objects with digital holography.
AB  - Digital holography has some desirable properties for refractometry of microscopic
      objects since it gives phase and amplitude information of an object in all depths
      of focus from one set of exposures. We show that the amplitude part of the image
      can be used to observe how the Becke lines move between different depths of focus
      and hence determine whether an object has a higher or a lower index of refraction
      than its surrounding medium, i.e., the sign of the relief. It is also shown that
      one single-phase image provides an independent technique to determine the sign of
      relief between an object and the surrounding medium.

PMID- 15449466
TI  - Limitation of the achievable signal-to-noise ratio in optical coherence
      tomography due to mismatch of the balanced receiver.
AB  - Owing to the limited spectral response of the fiber directional coupler used in a
      balanced optical coherence tomography configuration, the spectra are different in
      the two outputs. This affects unfavorably operation of the balanced photodetector
      unit. Excess photon noise makes a larger contribution than a directional coupler
      with a flat spectral response. A theoretical model is developed that shows that
      an optimum set of parameters may be defined to maximize the achievable signal-to
      noise ratio. The model leads to a redefinition of the effective noise bandwidth,
      which takes into account the nonflat response of the directional coupler used.
      The model also predicts a limitation on the signal-to-noise ratio even when the
      stray reflectances in the interferometer are brought to zero.

PMID- 15449467
TI  - Precision ranger for measuring large mechanical components.
AB  - We present a precision laser ranger system for the measurement of large
      manufactured components and structures. The system was developed based on a beat
      wave interferometry principle. The light source of this system is a frequency
      stabilized laser with a frequency stability of 1 x 10(-7) (in open air) or 10(-8)
      (in the laboratory). The laser operates in two longitudinal modes, and the two
      modes are generated in common resonator; therefore the two beams are naturally
      coaxial. The precision ranger system does not need a long guide or any heavy
      machinery. In this system an adaptive filter and a wavelet-transform program are
      used to improve the measurement accuracy. The system described here has a
      measuring range of 0-20 m and a measuring uncertainty of 30 microm/10 m.

PMID- 15449468
TI  - Signal modeling for low-coherence height-scanning interference microscopy.
AB  - We propose a computationally efficient theoretical model for low-coherence
      interferometric profilers that measure surface heights by scanning the optical
      path difference of the interferometer. The model incorporates both geometric and
      spectral effects by means of an incoherent superposition of ray bundles through
      the interferometer spanning a range of wavelengths, incident angles, and pupil
      plane coordinates. This superposition sum is efficiently performed in the
      frequency domain, followed by a Fourier transform to generate the desired
      simulated interference signal. Example applications include white-light
      interferometry, high-numerical-aperture microscopy with a near-monochromatic
      light source, and interference microscopy for thickness and topography analysis
      of thin-film structures and other complex surface features.

PMID- 15449469
TI  - Optical manipulation in combination with multiphoton microscopy for single-cell
      studies.
AB  - We demonstrate how optical tweezers can be incorporated into a multiphoton
      microscope to achieve three-dimensional imaging of trapped cells. The optical
      tweezers, formed by a cw 1064 nm Nd:YVO4 laser, were used to trap live yeast
      cells in suspension while the 4',6-diamidino-2-phenylindole-stained nucleus was
      imaged in three dimensions by use of a pulsed femtosecond laser. The trapped cell
      was moved in the axial direction by changing the position of an external lens,
      which was used to control the divergence of the trapping laser beam. This gives
      us a simple method to use optical tweezers in the laser scanning of confocal and
      multiphoton microscopes. It is further shown that the same femtosecond laser as
      used for the multiphoton imaging could also be used as laser scissors, allowing
      us to drill holes in the membrane of trapped spermatozoa.

PMID- 15449470
TI  - Simple lens axicon.
AB  - We present the design of a cemented doublet-lens axicon made from spherical
      surfaces only. Compared with diffractive axicons, refractive cone axicons, and
      earlier lens axicons with aspheric surfaces, this element is inexpensive and easy
      to manufacture even with large apertures. The lens axicon is based on the
      deliberate use of the spherical aberration of the surfaces. The design principles
      of the element and its characterization, numerically and experimentally, are
      presented in detail. Although performance was traded for simplicity and
      robustness, the results show that the lens axicon has the main axicon properties:
      a narrow, extended line focus of relatively constant width.

PMID- 15449471
TI  - Design and imaging performance of achromatic diffractive-refractive x-ray and
      gamma-ray Fresnel lenses.
AB  - Achromatic combinations of a diffractive phase Fresnel lens and a refractive
      correcting element have been proposed for x-ray and gamma-ray astronomy and for
      microlithography, but considerations of absorption often dictate that the
      refractive component be given a stepped profile, resulting in a double Fresnel
      lens. The imaging performance of corrected Fresnel lenses, with and without
      stepping, is investigated, and the trade-off between resolution and useful
      bandwidth in different circumstances is discussed. Provided that the focal ratio
      is large, correction lenses made from low atomic number materials can be used
      with x rays in the range of approximately 10-100 keV without stepping. The use of
      stepping extends the possibility of correction to higher-aperture systems, to
      energies as low as a few kilo electron volts, and to gamma rays of mega electron
      volt energy.

PMID- 15449472
TI  - Implementation of field lens arrays in beam-deflecting microlens array
      telescopes.
AB  - Laterally displaceable microlens array telescopes allow for variable and fast
      beam deflection. The generation of spurious light usually leads to a reduction of
      transfer efficiency with increasing displacement. We present the introduction of
      an array of field lenses on the back side of a recollimating microlens array that
      results in a reduced deflection angle dependency of transfer efficiency. A
      paraxial matrix formalism is used to prove the theoretical elimination of
      spurious light by use of a field lens array. The fabrication of well-aligned
      double-sided lens arrays by UV replication is discussed. Measurements of transfer
      efficiency with and without the use of field lens arrays are compared with the
      results of numerical wave-optic simulations.

PMID- 15449473
TI  - Holographic optical coherence imaging of rat osteogenic sarcoma tumor spheroids.
AB  - Holographic optical coherence imaging is a full-frame variant of coherence-domain
      imaging. An optoelectronic semiconductor holographic film functions as a
      coherence filter placed before a conventional digital video camera that passes
      coherent (structure-bearing) light to the camera during holographic readout while
      preferentially rejecting scattered light. The data are acquired as a succession
      of en face images at increasing depth inside the sample in a fly-through
      acquisition. The samples of living tissue were rat osteogenic sarcoma
      multicellular tumor spheroids that were grown from a single osteoblast cell line
      in a bioreactor. Tumor spheroids are nearly spherical and have radial symmetry,
      presenting a simple geometry for analysis. The tumors investigated ranged in
      diameter from several hundred micrometers to over 1 mm. Holographic features from
      the tumors were observed in reflection to depths of 500-600 microm with a total
      tissue path length of approximately 14 mean free paths. The volumetric data from
      the tumor spheroids reveal heterogeneous structure, presumably caused by necrosis
      and microcalcifications characteristic of some human avascular tumors.

PMID- 15449474
TI  - Dynamic target tracking with fringe-adjusted joint transform correlation and
      template matching.
AB  - Target tracking in forward-looking infrared (FLIR) video sequences is a
      challenging problem because of various limitations such as low signal-to-noise
      ratio (SNR), image blurring, partial occlusion, and low texture information,
      which often leads to missing targets or tracking nontarget objects. To alleviate
      these problems, we developed a novel algorithm that involves local-deviation
      based image preprocessing as well as fringe-adjusted joint-transform-correlation-
      (FJTC) and template-matching--(TM) based target detection and tracking. The local
      deviation-based preprocessing technique is used to suppress smooth texture such
      as background and to enhance target edge information. However, for complex
      situations such as the target blending with background, partial occlusion of the
      target, or proximity of the target to other similar nontarget objects, FJTC may
      produce a false alarm. For such cases, the TM-based detection technique is used
      to compensate FJTC breaking points by use of cross-correlation coefficients.
      Finally, a robust tracking algorithm is developed by use of both FJTC and TM
      techniques, which is called FJTC-TM technique. The performance of the proposed
      FJTC-TM algorithm is tested with real-life FLIR image sequences.

PMID- 15449475
TI  - Depth extraction by use of a rectangular lens array and one-dimensional elemental
      image modification.
AB  - Stereo matching, a technique for acquiring depth information from many planar
      images obtained by several cameras, was developed several decades ago. Recently a
      novel depth-extraction technique that uses a lens array instead of several
      cameras has attracted much attention because of the advantages offered by its
      compact system configuration. We present a novel depth-extraction method that
      uses a lens array consisting of vertically long rectangular lens elements. The
      proposed method rearranges the horizontal positions of the pixels from the
      collection of perspective images while it leaves the vertical positions of the
      pixels unchanged. To these rearranged images we apply a correlation-based
      multibaseline stereo algorithm in properly modified form. The main feature of the
      proposed method is the inverse dependency of the disparity in depth between
      horizontal and vertical directions. This inverse dependency permits the
      extraction of exact depth from extremely periodically patterned object scenes and
      reduces quantization error in the depth extraction.

PMID- 15449476
TI  - Comparison of defocusing and fractional Fourier transform in spectroholographic
      storage.
AB  - In spectroholographic storage systems the defocusing method is often used for
      spectrum uniformity and quality improvement of recorded information. The same
      purpose is served by the fractional Fourier transform (FRFT) storage system. To
      simplify the numerical analysis, we derive the expressions of the Fraunhofer
      spectrum and the reconstructed image at the detected plane (CCD) for both cases
      instead of using the Fresnel spectrum and the FRFT spectrum. The recording
      aperture, spectrum uniformity, and reconstructed information of both systems are
      investigated. A numerical comparison is also presented.

PMID- 15449477
TI  - High-transfer-rate high-capacity holographic disk data-storage system.
AB  - We describe the design and implementation of a high-data-rate high-capacity
      digital holographic storage disk system. Various system design trade-offs that
      affect density and data-rate performance are described and analyzed. In the
      demonstration system that we describe, high-density holographic recording is
      achieved by use of high-resolution short-focal-length optics and correlation
      shift multiplexing in photopolymer disk media. Holographic channel decoding at a
      1-Gbit/s data rate is performed by custom-built electronic hardware. A benchmark
      sustained optical data-transfer rate of 10 Gbits/s has been successfully
      demonstrated.

PMID- 15449478
TI  - Frequency-shifted optical feedback in a pumping laser diode dynamically amplified
      by a microchip laser.
AB  - Compared with conventional optical heterodyne detection, laser optical feedback
      imaging (LOFI) allows for a several orders of magnitude higher intensity
      modulation contrast. The maximum contrast amplification is typically 10(3) for a
      diode laser in the gigahertz range and 10(6) for a microchip laser in the
      megahertz range. To take advantage of the wavelength tunability of a laser diode
      and of the lower resonant detection frequency of a microchip laser, we used LOFI
      modulation induced by the frequency-shifted optical feedback in a laser diode as
      a modulated pumping power for a microchip laser for resonant dynamic
      amplification. In this way, we were able to transfer the optical feedback
      sensitivity of the laser diode to the megahertz range. Application to telemetry
      is also reported.

PMID- 15449479
TI  - Type II quasi-phase-matched sum-frequency mixing of diode lasers in KTiOPO4 with
      broad spectral and temperature acceptance bandwidths.
AB  - A 1500-nm-band laser signal is upconverted to the mid-visible part of the
      spectrum by quasi-phase matched, sum-frequency generation with an 800-nm-band
      laser pump in a periodically poled KTiOPO4. For an appropriate combination of the
      two fundamental wavelengths, an acceptance bandwidth of 40-60 nm cm for the pump
      wavelength is attainable simultaneously with a temperature acceptance bandwidth
      of 60-70 degrees C cm in an angularly noncritical condition. Using a distributed
      feedback laser at 1590 nm and a Fabry-Perot laser at 807 nm, we demonstrate a
      temperature tolerance as large as 60 degrees C with a 10-mm-long crystal.

PMID- 15449480
TI  - Use of equivalent spheres to model the relation between radar reflectivity and
      optical extinction of ice cloud particles.
AB  - The effect of ice crystal size and shape on the relation between radar
      reflectivity and optical extinction is examined. Discrete-dipole approximation
      calculations of 95-GHz radar reflectivity and ray-tracing calculations are
      applied to ice crystals of various habits and sizes. Ray tracing was used
      primarily to calculate optical extinction and to provide approximate information
      on the lidar backscatter cross section. The results of the combined calculations
      are compared with Mie calculations applied to collections of different types of
      equivalent spheres. Various equivalent sphere formulations are considered,
      including equivalent radar-lidar spheres; equivalent maximum dimension spheres;
      equivalent area spheres, and equivalent volume and equivalent effective radius
      spheres. Marked differences are found with respect to the accuracy of different
      formulations, and certain types of equivalent spheres can be used for useful
      prediction of both the radar reflectivity at 95 GHz and the optical extinction
      (but not lidar backscatter cross section) over a wide range of particle sizes.
      The implications of these results on combined lidar-radar ice cloud remote
      sensing are discussed.

PMID- 15449481
TI  - Performance capabilities of middle-atmosphere temperature lidars: comparison of
      Na, Fe, K, Ca, Ca+, and Rayleigh systems.
AB  - The measurement accuracies of modern resonance fluorescence and Rayleigh
      temperature lidars are limited primarily by photon noise. The narrowband three
      frequency fluorescence technique is shown to perform within a few decibels of the
      theoretical optimum at night for both temperature and wind observations. These
      systems also exhibit good performance during the day because the fluorescence
      wavelengths of Na, Fe, K, Ca, and Ca+ all correspond to strong solar Fraunhofer
      lines, where sky brightness is attenuated by a factor of 5 or more. Whereas Na
      systems achieve the highest signal-to-noise ratios for mesopause region
      observations (80-105 km), the three-frequency Fe system is attractive because it
      performs well as both a fluorescence and a Rayleigh lidar throughout the middle
      atmosphere at approximately 25-110 km.

PMID- 15449482
TI  - Effects of molecular and particle scatterings on the model parameter for remote
      sensing reflectance.
AB  - For optically deep waters, remote-sensing reflectance (r(rs)) is traditionally
      expressed as the ratio of the backscattering coefficient (b(b)) to the sum of
      absorption and backscattering coefficients (a + b(b)) that multiples a model
      parameter (g, or the so-called f'/Q). Parameter g is further expressed as a
      function of b(b)/(a + b(b)) (or b(b)/a) to account for its variation that is due
      to multiple scattering. With such an approach, the same g value will be derived
      for different a and b(b) values that provide the same ratio. Because g is
      partially a measure of the angular distribution of upwelling light, and the
      angular distribution from molecular scattering is quite different from that of
      particle scattering; g values are expected to vary with different scattering
      distributions even if the b(b)/a ratios are the same. In this study, after
      numerically demonstrating the effects of molecular and particle scatterings on
      the values of g, an innovative r(rs) model is developed. This new model expresses
      r(rs) in two separate terms: one governed by the phase function of molecular
      scattering and one governed by the phase function of particle scattering, with a
      model parameter introduced for each term. In this way the phase function effects
      from molecular and particle scatterings are explicitly separated and accounted
      for. This new model provides an analytical tool to understand and quantify the
      phase-function effects on r(rs), and a platform to calculate r(rs) spectrum
      quickly and accurately that is required for remote-sensing applications.

PMID- 15449483
TI  - High-resolution tunable mid-infrared spectrometer based on difference-frequency
      generation in AgGaS2.
AB  - We have built a high-resolution and high-signal-to-noise ratio spectrometer for
      line shape studies of greenhouse gases in the mid infrared. The infrared
      radiation is generated in a AgGaS2 nonlinear crystal by the well-known difference
      frequency method. The choice of crystal is explained, and a brief literature
      review is presented. With two tunable dye lasers and a type I, 90 degrees phase
      matching geometry, the infrared is continuously tunable from 7 to 9 microm when
      Rhodamine 6G and Sulforhodamine 640 dyes are used. The total infrared power
      exceeds 30 nW and is limited by both the damage threshold and thermal loading of
      the crystal. Phase-sensitive detection allows us to reach signal-to-noise ratios
      in excess of 3500:1 while maintaining an instrumental linewidth of 1.5 MHz.
      However, we show that the spectrometer may be used to measure the positions of
      spectral lines within +/-400 kHz.

PMID- 15449484
TI  - Anaesthetist or intensivist?

PMID- 15449485
TI  - Quality of stroke care in 2004.

PMID- 15449486
TI  - Training in obstetrics and gynaecology in the UK: present and future.

PMID- 15449487
TI  - Training in obstetrics and gynaecology in The Netherlands.

PMID- 15449488
TI  - Training the future consultant in obstetrics and gynaecology.

PMID- 15449489
TI  - Causes of a widened mediastinum: a pictorial review.

PMID- 15449490
TI  - Fracture protection in osteoporosis with risedronate.

PMID- 15449491
TI  - The spectrum of autistic disorders.

PMID- 15449492
TI  - Atrial fibrillation. 2: Management.

PMID- 15449493
TI  - Early care of severe sepsis and multiple organ failure in children.

PMID- 15449494
TI  - Good at medicine, pity about the rest.

PMID- 15449495
TI  - A young woman with urinary symptoms, septicaemia and a pectoral muscle abscess.

PMID- 15449496
TI  - Ogilvie's syndrome: a rare complication of inguinal hernia repair.

PMID- 15449497
TI  - Unusual site and presentation of a neuroendocrine tumour.

PMID- 15449498
TI  - Effecting change in the NHS.

PMID- 15449499
TI  - Effecting change in the NHS.

PMID- 15449500
TI  - Effecting change in the NHS.

PMID- 15449501
TI  - Should a fibreoptic bronchoscope be used to confirm double lumen tube placement?

PMID- 15449502
TI  - What dreams are made of.

PMID- 15449503
TI  - Sweet, elusive sleep.

PMID- 15449504
TI  - Get ready for e-medicine.

PMID- 15449505
TI  - More than a statin.

PMID- 15449506
TI  - Radiographic assessment of osteoarthritis in population studies: whither Kellgren
      and Lawrence?

PMID- 15449507
TI  - Intraosseous thrombosis in osteoarthritis: association or causation?

PMID- 15449508
TI  - Precision of joint space width measurement in knee osteoarthritis from digital
      image analysis of high definition macroradiographs.
AB  - The precision of joint space width (JSW) measurements from plain film radiographs
      of the knee is limited by poor radio-anatomical positioning of the joint and/or
      insensitive methods of measurement. These limitations were overcome by
      establishing a precise radio-anatomical position for standing loaded and weight
      bearing tunnel views of the knee, using the advantages of high definition
      macroradiography and a new computerized method for automatic JSW measurement from
      digitized macroradiographs of the knee. Reproducibility of JSW measurements was
      obtained from macroradiographs of knees of five post-mortem subjects and 12
      patients with osteoarthritis (OA). JSW measurements were altered more by vertical
      than by horizontal misalignment of the X-ray beam relative to the joint space. In
      OA knees with medial compartment involvement, JSW measurements were more
      reproducible in the medial than lateral compartments in both radiographic views.
      In the medial compartment, the coefficient of variation for joint repositioning
      was 1% for minimum and 2% for average JSW, and for inter- and intraobserver
      errors, it was < 1% for both JSW measurements. The precision of this method will
      permit quantification of changes in JSW associated with disease progression and
      the treatment of OA.

PMID- 15449509
TI  - Intraosseous thrombosis in ischemic necrosis of bone and osteoarthritis.
AB  - It has been proposed that nontraumatic ischemic necrosis of bone (INB) is a
      result of lipid associated intraosseous thrombosis. A histological study of 15
      patients with INB confirmed the presence of intravascular lipid and thrombosis in
      the vessels of the femoral head. A similar analysis of 11 patients with primary
      osteoarthritis (OA) showed similar changes at lower levels. These changes were
      not observed in seven control femoral heads. The possibility that both INB and OA
      result from intraosseous thrombosis is discussed.

PMID- 15449510
TI  - Intra-articular sodium hyaluronate in osteoarthritis of the knee: a multicenter,
      double-blind study.
AB  - The efficacy and the safety of intra-articular injections of sodium hyaluronate
      were studied in patients with osteoarthritis of the knee in a randomized
      multicenter double-blind study. Two hundred and nine patients received five
      injections of either 25 mg hyaluronate/2.5 ml (verum, N = 102) or 0.25 mg
      hyaluronate/2.5 ml (control, N = 107) at weekly intervals. Seven patients in each
      group were excluded from the protocol-correct efficacy analysis. The Lequesne
      Index, the first main criterion, showed a significant superiority of the verum
      treated patients after the third injection up to the final follow-up examination
      9 weeks after the last injection (MANOVA, P < 0.025). The consumption of
      paracetamol was defined as a complementary main criterion that did not reveal
      significant differences between the treatment groups. Most of the individual
      secondary endpoints demonstrated a much better response to the active treatment
      without reaching the significance level in the intergroup comparisons for the
      single time-points. Side-effects were confined to local reactions of minor
      severity and short duration in four patients (six events) of the verum group and
      in five patients of the control group. Clinical chemistry and hematology remained
      essentially unchanged.

PMID- 15449511
TI  - Hindlimb loading, morphology and biochemistry of articular cartilage in the ACL
      deficient cat knee.
AB  - The cat hindlimb is the best studied animal model of neuromuscular control,
      muscle mechanics/muscle morphology, and locomotor kinematics. Therefore, this
      model offers itself for intervention studies, where a musculoskeletal parameter
      is perturbed and the effects of this perturbation are compared with normal
      function. The objective of this study was to describe the effects of anterior
      cruciate ligament (ACL) transection in the cat knee and to correlate hindlimb
      loading with morphological and biochemical changes of articular cartilage. A
      distinct unloading of the deficient hindlimb was found when compared with the
      nonoperated hindlimb immediately after ACL transection, and persisted for about
      16-18 weeks. Beyond about 18 weeks post-ACL transection, hindlimb loading
      returned to the symmetric pattern observed before surgery. In accordance with the
      expectations from the force-platform results, a decrease in muscle mass was found
      from muscles of the experimental hindlimb when compared to the mass of muscles
      from the contralateral hindlimb. This decrease of muscle mass was largest at 4
      weeks and smallest at 35 weeks post-ACL transection. At 12 and 35 weeks post-ACL
      transection, cell density was increased and absolute amounts of hexuronic acid
      were elevated in the articular cartilage of the experimental knee compared with
      the corresponding values of the contralateral knee. Progressive changes of the
      articular cartilage towards osteoarthritis (OA) were not observed in the time
      frame of this experiment. The results suggest that anterior cruciate ligament
      transection in the cat produces initial changes in the knee that are similar to
      those observed previously in the dog and rabbit.

PMID- 15449512
TI  - Alterations of proteoglycan synthesis in rabbit articular cartilage induced by
      intra-articular injection of papain.
AB  - In order to investigate the biochemical alteration of proteoglycan (PG) synthesis
      during cartilage repair, reversible destruction was induced by injecting papain
      into the knee joint cavity of rabbits. The PG synthesis in the cartilage was
      examined using Na2 35SO4 and high performance liquid chromatography (HPLC). PGs
      labeled with 35SO4(2-) (35S-PGs) were extracted from normal and papain-treated
      cartilage, and the amount of synthesis, ability to aggregate with hyaluronan
      (HA), and the composition of glycosaminoglycan and chondroitin sulfate isomer
      labeled with 35SO4(2-) (35S-GAG and 35S-CS isomer) were analyzed. Synthesis of
      35S-PGs, especially those that were unable to aggregate with HA (nonaggregating
      35S-PGs), increased in papain-treated cartilage compared with that in normal
      cartilage. The acceleration and qualitative change in PG synthesis in the papain
      treated cartilage are considered to be responses to the supplementation of the
      loss of cartilage PGs induced by papain. The compositions of 35S-GAG and 35S-CS
      isomer of the nonaggregating 35S-PGs differed from those of 35S-PGs which were
      able to aggregate with HA (aggregating 35S-PGs) in the papain-treated cartilage
      as well as in the normal cartilage. However, the compositions of both
      nonaggregating and aggregating 35S-PGs in the papain-treated and normal cartilage
      were similar. These results indicate that most of the nonaggregating 35S-PGs in
      papain-treated cartilage have properties similar to those in normal cartilage and
      are not simple degradation products of aggregating 35S-PGs; they also suggest
      that the supplementary reaction for PG content in the cartilage during its repair
      process is not simple acceleration in PG turn-over but the enhancement of PG
      synthesis accompanied by alterations in aggregating ability and the compositions
      of GAG and CS isomer.

PMID- 15449513
TI  - The very early identification of autism: outcome to age 4 1/2-5.
AB  - Forty-nine 2 years olds with social and language characteristics suggestive of
      autism were identified by community professionals and screening tools, then given
      a diagnostic assessment and reexamined at age 4 1/2. Agreement between autism
      clinic and screenings was high, with 88% receiving a diagnosis on the autism
      spectrum. The children were lower functioning relative to the autism population,
      thus more likely to be identified early. Reliability of diagnoses from 2 1/2 to 4
      1/2 was high with 79% staying in the same diagnostic category, but more so for
      clear autism than for PDDNOS. About a third improved over 20 IQ points and
      similar number similarly declined. Changes were not related to amount or type of
      intervention but were related to the children's characteristics. Higher
      functioning children with milder autism were the most improved.

PMID- 15449514
TI  - Psychiatric symptoms in preschool children with PDD and clinic and comparison
      samples.
AB  - OBJECTIVE: This study describes and compares the severity of DSM-IV symptoms in
      preschool children with diagnosed pervasive developmental disorder (PDD), clinic
      controls, and two community-based samples. METHOD: Parents (/and teachers)
      completed the early child inventory-4 (ECI-4), a DSM-IV-referenced rating scale
      for four samples: PDD (n = 172/160) and nonPDD psychiatric clinic referrals
      (n=135/101) and youngsters in regular (n=507/407) and special (n =64/140) early
      childhood programs. Children ranged in age from 3 to 5 years old. RESULTS: With
      the exception of conduct problems, the PDD group generally received higher
      symptom severity ratings than the regular early childhood group, but the pattern
      of differences compared with the other two groups often varied by type of symptom
      and informant. Teachers rated the PDD and nonPDD clinic groups as having equally
      severe ADHD and oppositional defiant disorder symptoms. Teachers rated the PDD
      group as having more severe anxiety and depression symptoms than parents. The
      Asperger group was rated by both informants as more oppositional than the autism
      and PDDNOS subgroups. Teachers rated males in the regular early childhood sample
      as having more severe ADHD and aggressive symptoms than females, but this was not
      the case for the PDD sample. CONCLUSION: Preschoolers with PDD exhibit more
      severe DSM-IV psychiatric symptoms than children in regular and special early
      childhood programs, and to some extent nonPDD psychiatric referrals. The concept
      of comorbidity warrants further exploration, as does informant-specific syndromes
      as validators of diagnostic constructs.

PMID- 15449515
TI  - Effects on communicative requesting and speech development of the Picture
      Exchange Communication System in children with characteristics of autism.
AB  - Few studies on augmentative and alternative communication (AAC) systems have
      addressed the potential for such systems to impact word utterances in children
      with autism spectrum disorders (ASD). The Picture Exchange Communication System
      (PECS) is an AAC system designed specifically to minimize difficulties with
      communication skills experienced by individuals with ASD. The current study
      examined the role of PECS in improving the number of words spoken, increasing the
      complexity and length of phrases, and decreasing the non-word vocalizations of
      three young children with ASD and developmental delays (DD) with related
      characteristics. Participants were taught Phases 1-4 of PECS (i.e., picture
      exchange, increased distance, picture discrimination, and sentence construction).
      The results indicated that PECS was mastered rapidly by the participants and word
      utterances increased in number of words and complexity of grammar.

PMID- 15449516
TI  - Teaching VOCA use as a communicative repair strategy.
AB  - Students with developmental disabilities often rely on prelinguistic behavior
      (e.g., reaching, leading) to communicate. When listeners fail to attend to
      prelinguistic behaviors, students may benefit from responding with an alternative
      form of communication to repair the breakdown. In the present study, we taught
      two students with developmental disabilities to repair communicative breakdowns
      by using a voice-output communication aid (VOCA). Intervention occurred at
      morning snack time when the students had the opportunity to access preferred
      items through prelinguistic behavior (e.g., reaching, guiding). Breakdowns
      occurred when the listener failed to attend to the student's initial request.
      Effects of the intervention were evaluated in a multiple-baseline design across
      subjects. Both students learned to use the VOCA to repair communicative
      breakdowns. As VOCA use was acquired as a repair strategy, the students also
      began to use the device to initiate requests when there had been no breakdown in
      communication. The intervention appeared to be an effective approach for
      supplementing prelinguistic behaviors with an additional option for communicating
      a request.

PMID- 15449517
TI  - Alternative seating for young children with Autism Spectrum Disorder: effects on
      classroom behavior.
AB  - A single subject, withdrawal design was used to investigate the effects of
      therapy balls as seating on engagement and in-seat behavior of young children
      with Autism Spectrum Disorder (ASD). In addition, social validity was assessed to
      evaluate teachers' opinions regarding the intervention. During baseline and
      withdrawal (A phases) participants used their typical classroom seating device
      (chair, bench or carpet square). During the intervention (B phases) participants
      sat on therapy balls. Results indicated substantial improvements in engagement
      and in-seat behavior when participants were seated on therapy balls. Social
      validity findings indicated that the teachers' preferred the therapy balls. This
      study suggests therapy balls as classroom seating may facilitate engagement and
      in-seat behavior and create opportunities to provide effective instruction.

PMID- 15449518
TI  - A comparison of eating behaviors between children with and without autism.
AB  - Although clinicians typically assume that feeding problems co-exist with a
      diagnosis of autism, no previous research has compared the eating behavior of
      children with autism to typically developing children. This study compared
      caregiver report of eating problems of children with and without autism on a
      standardized questionnaire. The questionnaire included items pertaining to food
      refusal and acceptance patterns as well as food presentation requirements.
      Caregivers were also asked to complete a food inventory that indicated the number
      of foods eaten within each food group for both the child and the family. Results
      indicated children with autism have significantly more feeding problems and eat a
      significantly narrower range of foods than children without autism.

PMID- 15449519
TI  - Self-regulation and affective expression during play in children with autism or
      Down Syndrome: a short-term longitudinal study.
AB  - Our study examined stability of self-regulation and affective expression in
      children with autism or Down syndrome over a 2 year period. A behaviorally
      anchored rating scale was used to assess a self-regulation factor (attention,
      adaptability, object orientation, and persistence), negative affect factor
      (hostility, irritability, and compliance), and positive affect factor (positive
      affect, affective sharing, and dull affect) from videotapes of play sessions
      involving each child and his or her mother. The patterns of ratings within each
      group were similar from time 1 to time 2, with the autism group showing more
      deviant ratings on measures of self-regulation and affective sharing. From time 1
      to time 2, children with autism showed relatively high stability for the self
      regulation factor, but less stability than children with Down syndrome for all
      three factors.

PMID- 15449520
TI  - The use and understanding of virtual environments by adolescents with autistic
      spectrum disorders.
AB  - The potential of virtual environments for teaching people with autism has been
      positively promoted in recent years. The present study aimed to systematically
      investigate this potential with 12 participants with autistic spectrum disorders
      (ASDs), each individually matched with comparison participants according to
      either verbal IQ or performance IQ, as well as gender and chronological age.
      Participants practised using a desktop 'training' virtual environment, before
      completing a number of tasks in a virtual cafe. We examined time spent completing
      tasks, errors made, basic understanding of the representational quality of
      virtual environments and the social appropriateness of performance. The use of
      the environments by the participants with ASDs was on a par with their PIQ
      matched counterparts, and the majority of the group seemed to have a basic
      understanding of the virtual environment as a representation of reality. However,
      some participants in the ASD group were significantly more likely to be judged as
      bumping into, or walking between, other people in the virtual scene, compared to
      their paired matches. This tendency could not be explained by executive
      dysfunction or a general motor difficulty. This might be a sign that
      understanding personal space is impaired in autism. Virtual environments might
      offer a useful tool for social skills training, and this would be a valuable
      topic for future research.

PMID- 15449521
TI  - Difficulties with "executive functions".

PMID- 15449522
TI  - [Quality of life in patients with atrial fibrillation].

PMID- 15449523
TI  - [Quality of life of patients given pharmacological treatment for atrial
      fibrillation].

PMID- 15449524
TI  - [Microchimerism--a possible cause of autoimmune disease?].

PMID- 15449525
TI  - [Problem-oriented drug information: the RELIS database, a free drug information
      on the Internet for Scandinavian health professionals].

PMID- 15449526
TI  - [Botulinum toxin treatment of spastic cerebral palsy].

PMID- 15449527
TI  - [Forensic psychiatric patients: Diagnoses, substance abuse, and criminal
      activity].

PMID- 15449528
TI  - [Cochlear implants to deaf adults: psychosocial consequences].

PMID- 15449529
TI  - [Psychiatric hospitalizations among survivors of cancer in childhood or
      adolescence].

PMID- 15449530
TI  - [Quality of life of non-pharmacologically treated patients with atrial
      fibrillation].

PMID- 15449531
TI  - [Spontaneous pneumothorax and fibrosing pulmonary disease].

PMID- 15449532
TI  - [Ethylene glycol poisoning. A diagnostic and therapeutic dilemma].

PMID- 15449533
TI  - [Pityriasis rubra pilaris. A characteristic but rare skin disease].

PMID- 15449534
TI  - [Severe obstructive sleep apnea in a child with craniofacial anomaly].

PMID- 15449535
TI  - [Developing specialist health care for older people: a challenge for the European
      Union].

PMID- 15449536
TI  - [Breast cancer, mammography screening and hormone therapy].

PMID- 15449537
TI  - [Does estrogen reduce the risk of breast cancer?].

PMID- 15449538
TI  - [Is drug therapy of Alzheimer disease ineffective?].

PMID- 15449539
TI  - [Terminology in connection with antigen and antibody assays].

PMID- 15449540
TI  - Molecular evolution of PAS domain-containing proteins of filamentous
      cyanobacteria through domain shuffling and domain duplication.
AB  - When the entire genome of a filamentous heterocyst-forming N2-fixing
      cyanobacterium, Anabaena sp. PCC 7120 (Anabaena) was determined in 2001, a large
      number of PAS domains were detected in signal-transducing proteins. The draft
      genome sequence is also available for the cyanobacterium, Nostoc punctiforme
      strain ATCC 29133 (Nostoc), that is closely related to Anabaena. In this study,
      we extracted all PAS domains from the Nostoc genome sequence and analyzed them
      together with those of Anabaena. Clustering analysis of all the PAS domains gave
      many specific pairings, indicative of evolutionary conservations. Ortholog
      analysis of PAS-containing proteins showed composite multidomain architecture in
      some cases of conserved domains and domains of disagreement between the two
      species. Further inspection of the domains of disagreement allowed us to trace
      them back in evolution. Thus, multidomain proteins could have been generated by
      duplication or shuffling in these cyanobacteria. The conserved PAS domains in the
      orthologous proteins were analyzed by structural fitting to the known PAS
      domains. We detected several subclasses with unique sequence features, which will
      be the target of experimental analysis.

PMID- 15449542
TI  - Complete nucleotide sequence of the sugarcane (Saccharum officinarum) chloroplast
      genome: a comparative analysis of four monocot chloroplast genomes.
AB  - The complete nucleotide sequence of the chloroplast genome of sugarcane
      (Saccharum officinarum) has been determined. It is a circular double-stranded DNA
      molecule, 141,182 bp in size, and is composed of a large single copy of 83,048
      bp, a small single copy of 12,544 bp, and a pair of inverted repeat regions of
      22,795 bp each. A comparative analysis among monocots showed that the sugarcane
      chloroplast genome was very similar to maize but not to rice or wheat. Between
      sugarcane and maize at the rps16-trnQ (UUG) region, however, a length
      polymorphism was identified. With regard to insertions/deletions equal to or
      longer than 5 bp, a total of 53 insertion and 31 deletion events were identified
      in the sugarcane chloroplast genome. Of the 84 loci identified, a pair of direct
      repeat sequences was located side by side in a tandem fashion in 47 loci (56.0%).
      A recombination event during plant evolution is discussed at two sites between
      the sugarcane and tobacco chloroplast genomes.

PMID- 15449543
TI  - A proteomic approach to identification of transmembrane proteins and membrane
      anchored proteins of Arabidopsis thaliana by peptide sequencing.
AB  - A proteomic approach was developed for the identification of membrane-bound
      proteins of Arabidopsis thaliana. A subcellular fraction enriched in vacuolar
      membranes was prepared from 4-week-old plants and was washed with various agents
      to remove peripheral membrane proteins and contaminating soluble proteins. The
      remaining membrane-bound proteins were then subjected to proteomic analysis.
      Given that these proteins were resolved poorly by standard two-dimensional gel
      electrophoresis, we subjected them instead to SDS-polyacrylamide gel
      electrophoresis and to protein digestion within gel slices with
      lysylendopeptidase. The resulting peptides were separated by reverse-phase high
      performance liquid chromatography and subjected to Edman sequencing. From the 163
      peptide peaks analyzed, 69 peptide sequences were obtained, 64 of which were
      informative. The proteins corresponding to these peptide sequences were
      identified as belonging to 42 families, including two subfamilies, by comparison
      with the protein sequences predicted from annotation of the A. thaliana genome. A
      total of 34 proteins was identified definitively with protein-specific peptide
      sequences. Transmembrane proteins detected in the membrane fraction included
      transporters, channels, receptors, and unknown molecules, whereas the remaining
      proteins, categorized as membrane-anchored proteins, included small GTPases,
      GTPase binding proteins, heat shock protein 70-like proteins, ribosomal proteins,
      and unknown proteins. These membrane-anchored proteins are likely attached to
      membranes by hydrophobic anchor molecules or through tight association with other
      membrane-bound proteins. This proteomic approach has thus proved effective for
      the identification of membrane-bound proteins.

PMID- 15449544
TI  - Mitochondrial genome of the Komodo dragon: efficient sequencing method with
      reptile-oriented primers and novel gene rearrangements.
AB  - The mitochondrial genome of the Komodo dragon (Varanus komodoensis) was nearly
      completely sequenced, except for two highly repetitive noncoding regions. An
      efficient sequencing method for squamate mitochondrial genomes was established by
      combining the long polymerase chain reaction (PCR) technology and a set of
      reptile-oriented primers designed for nested PCR amplifications. It was found
      that the mitochondrial genome had novel gene arrangements in which genes from
      NADH dehydrogenase subunit 6 to proline tRNA were extensively shuffled with
      duplicate control regions. These control regions had 99% sequence similarity over
      700 bp. Although snake mitochondrial genomes are also known to possess duplicate
      control regions with nearly identical sequences, the location of the second
      control region suggested independent occurrence of the duplication on lineages
      leading to snakes and the Komodo dragon. Another feature of the mitochondrial
      genome of the Komodo dragon was the considerable number of tandem repeats,
      including sequences with a strong secondary structure, as a possible site for the
      slipped-strand mispairing in replication. These observations are consistent with
      hypotheses that tandem duplications via the slipped-strand mispairing may induce
      mitochondrial gene rearrangements and may serve to maintain similar copies of the
      control region.

PMID- 15449545
TI  - Prediction of the coding sequences of mouse homologues of FLJ genes: the complete
      nucleotide sequences of 110 mouse FLJ-homologous cDnas identified by screening of
      terminal sequences of cDNA clones randomly sampled from size-fractionated
      libraries.
AB  - We have been conducting a mouse cDNA project to predict protein-coding sequences
      of mouse KIAA-homologous genes since 2001. As an extension of this project, we
      also started to accumulate mouse cDNA clones homologous to the human FLJ cDNA
      clones which are another long cDNA resource produced in our institute. We have
      isolated the cDNA clones from size-fractionated cDNA libraries derived from five
      different mouse tissues and natural killer T-cells. Although the human FLJ cDNA
      clones were originally derived from human spleen libraries, one-third of their
      mouse homologues were obtained from the brain library. We designated these
      homologues "mFLJ" plus a 5-digit number and herein characterized 110 mFLJ cDNA
      clones. We assigned an integrity of the CDSs from the comparison of the 110 cDNA
      clones with the corresponding human FLJ cDNA clones. The average size of the 110
      mouse cDNA sequences was 3.8 kb and that of the deduced amino acid sequences from
      their longest CDS in each cDNA was 663 amino acid residues. Homology and/or motif
      search against public databases revealed new domains and/or motifs in 26 mFLJ
      gene products which provide additional speculation regarding the function of FLJ
      genes.

PMID- 15449541
TI  - The minimal eukaryotic ribosomal DNA units in the primitive red alga
      Cyanidioschyzon merolae.
AB  - Cyanidioschyzon merolae is a small unicellular red alga that is considered to
      belong to one of the most deeply branched taxa in the plant kingdom. Its genome
      size is estimated to be 16.5 Mbp, one of the smallest among free-living
      eukaryotes. In the nucleus containing this small genome, one nucleolus is clearly
      observed, but the molecular basis for the intranuclear structure including
      ribosomal DNA organization is still unclear. We constructed a bacterial
      artificial chromosome library for C. merolae 10D composed of two subsets with
      different insert size distributions. The two subsets have average insert sizes of
      97 and 48 kb, representing 10.0- and 6.9-fold genome-equivalent coverage of the
      haploid genome, respectively. For application to whole-genome shotgun sequencing,
      the termini of each clone were sequenced as sequence-tagged connectors and mapped
      on the contigs assigned to chromosomes. Screening for rRNA genes by conventional
      colony hybridization with high-density filter blots and subsequent sequencing
      revealed that the C. merolae genome contained the smallest number of ribosomal
      DNA units among all the eukaryotes examined to date. They consist of only 3
      single units of rRNA genes distributed on separate chromosomal loci, representing
      an implication for concerted evolution. Based on these results, the origin and
      evolution of the nucleolus are discussed.

PMID- 15449546
TI  - Mitochondrial DNA sequences of five squamates: phylogenetic affiliation of
      snakes.
AB  - Complete or nearly complete mitochondrial DNA sequences were determined from four
      lizards (Western fence lizard, Warren's spinytail lizard, Terrestrial arboreal
      alligator lizard, and Chinese crocodile lizard) and a snake (Texas blind snake).
      These genomes had a typical gene organization found in those of most mammals and
      fishes, except for a translocation of the glutamine tRNA gene in the blind snake
      and a tandem duplication of the threonine and proline tRNA genes in the spinytail
      lizard. Although previous work showed the existence of duplicate control regions
      in mitochondrial DNAs of several snakes, the blind snake did not have this
      characteristic. Phylogenetic analyses based on different tree-building methods
      consistently supported that the blind snake and a colubrid snake (akamata) make a
      sister clade relative to all the lizard taxa from six different families. An
      alternative hypothesis that snakes evolved from a lineage of varanoids was not
      favored and nearly statistically rejected by the Kishino-Hasegawa test. It is
      therefore likely that the apparent similarity of the tongue structure between
      snakes and varanoids independently evolved and that the duplication of the
      control region occurred on a snake lineage after divergence of the blind snake.

PMID- 15449547
TI  - Virtual-SAGE: a new approach to EST data analysis.
AB  - We present a computer program, termed V-SAGE (Virtual-SAGE), designed to
      facilitate the analysis of gene expression profiles by combining elements of SAGE
      (Serial Analysis of Gene Expression) with high-throughput EST analysis. The
      program re-iteratively correlates sequence tags adjacent to poly(A) tail sequence
      strings with a second or several tags located within the cDNA adjacent to the
      recognition sequences of frequently-cutting endonucleases. By recording tags and
      their distance, the program generates an expression profile from large numbers of
      sequences, groups sequences according to tags, and identifies alternatively
      spliced transcripts as well as transcripts that are characterized by 3'-UTR
      sequences of different length. We discuss the application of V-SAGE to a
      collection of corn root segment transcripts.

PMID- 15449548
TI  - [Results of the first Chilean registry of unstable angina. Clinical features,
      risk profile and treatment].
AB  - BACKGROUND: From January 2000 to June 2002, the first Chilean registry of
      unstable angina was carried out, with the participation of 15 hospitals. AIM: To
      report the clinical and demographic features of 600 patients with unstable
      angina, their risk profile and prognosis. MATERIAL AND METHODS: The inclusion
      criteria for this prospective registry were a history of recent onset of chest
      pain (<48 hours) or a change in the character of previous angina, associated to
      ischemic electrocardiographic changes and/or positive markers of myocardial
      damage. RESULTS: Mean age of the patients was 65 years and 37% were women. Among
      coronary risk factors, 63% had hypertension, 27% had diabetes, 52% had
      dyslipidemia, 31% smoked and 21% had a family history of atherosclerosis. On
      admission 94% of patients had chest pain, associated to ST segment depression in
      44%, negative T waves in 28% and positive markers of myocardial damage in 30%.
      Fifty seven percent received intravenous nitroglycerin, 47% received oral
      nitrates, 69% beta blockers and 15%, calcium antagonists. Antithrombotic therapy
      included aspirin in 96%, heparin in 74%, ticlodipine or clopidogrel in 19% and
      IIb/IIIa inhibitors in 12%. A coronary angiogram was performed in 52%,
      angioplasty in 25% and coronary bypass surgery in 13%. Hospital mortality was
      2.6%. The incidence of new ischemic events was: myocardial infarction in 2.8%
      recurrent ischemia in 9.5% and refractory ischemia in 2%. The incidence of
      adverse events increased according to a higher risk profile. CONCLUSIONS: The
      demographic and clinical features, treatment and mortality of these patients are
      similar to those reported in international registries, with a low mortality rate.

PMID- 15449549
TI  - [Effects of acute octreotide infusion on renal function in patients with
      cirrhosis and portal hypertension].
AB  - BACKGROUND: Octreotide is used in the treatment of acute variceal bleeding, based
      on its inhibitory effects of post-prandial splanchnic hyperemia and splanchnic
      venoconstriction. The consequences of these haemodynamic changes on renal
      circulation are not well known in cirrhotic patients. AIM: To evaluate the
      effects of acute octreotide administration on several parameters of renal
      function, including free water clearance, in patients with cirrhosis with or
      without ascites. PATIENTS AND METHODS: Twenty cirrhotic patients, Child-Pugh A
      orB, with or without ascites, with esophageal varices, normal renal function and
      free of medications (vasoactive drugs or diuretics) were assigned to 2 different
      protocols. Protocol 1: 10 patients were randomized to receive octreotide or
      placebo, as a bolus followed by a continuous infusion. Glomerular filtration rate
      (GFR) and renal plasma flow (PRF) were measured, in basal conditions and during
      the drug or placebo administration. Protocol 2: 10 additional patients were
      randomized in the same way and free water clearance and urinary sodium excretion
      were again measured in the basal period and during the drug or placebo infusion.
      RESULTS: After octreotide or placebo administration no significant changes were
      observed neither in GFR nor in PRF. The free water clearance decreased
      significantly during octreotide administration (3.12 ml/min+/-1.04 SE vs 0.88+/
      0.39, p<.03). In both protocols no changes in mean arterial pressure were
      observed. CONCLUSIONS: Acute administration of octreotide to cirrhotic patients
      with portal hypertension, with or without ascites, did not produce any change in
      glomerular filtration rate or in estimated renal plasm blood flow. However the
      free water clearance decreased significantly. This effect, under chronic
      administration, could be clinically important and deserves further studies.

PMID- 15449550
TI  - [Antimicrobial activity of actinomycetes isolated from aquatic environments in
      southern Chile].
AB  - BACKGROUND: The easy access and inappropriate use of antimicrobials led to
      selection and spread of resistant microorganisms strains. It is imperative to
      search for new and more effective antimicrobials. One strategy is the screening
      of metabolites produced by microorganisms found in the environment. Actinomycetes
      are a potential source of new drugs. AIM: To isolate actinomycetes from sediments
      of Chilean rivers and lakes and to screen them for antimicrobial activity against
      reference bacterial strains and pathogenic fungi. MATERIAL AND METHODS:
      Actinomycetes were isolated from sediment samples, using casein-starch agar. The
      antimicrobial activity against 3 bacterial species and 7 fungal species was
      tested using the disc diffusion method. For the extraction of active metabolites,
      culture broths of antagonistic actinomycetes were extracted with organic solvents
      followed by testing the antibiotic activity. RESULTS: A total of 62 strains of
      actinomycetes were isolated, mainly Streptomyces sp (83.9%). Thirty six strains
      (58.1%) showed antimicrobial activity, mainly against Bacillus subtilis and
      Candida albicans. Some isolates inhibited a wide spectrum of indicator strains,
      like LRI 4A strain (Streptomyces sp) that inhibited Bacillus subtilis, Candida
      albicans and 4 filamentous fungi. CONCLUSIONS: Lakes and rivers of Southern Chile
      are an important reservoir of antagonistic actinomycetes, a potential source of
      new drugs.

PMID- 15449551
TI  - [Nutcracker esophagus. Analysis of 80 patients].
AB  - BACKGROUND: The nutcracker esophagus, a primary motor disorder, is frequently
      associated with noncardiac chest pain. AIM: To study the clinical, endoscopic,
      manometric, and pathological features and 24 h acid reflux in patients with
      nutcracker esophagus. PATIENTS AND METHODS: Eighty patients (63 females, aged 26
      to 70 years) with nutcracker esophagus, defined as the presence of contraction
      waves of more than 180 mmHg in the esophageal manometry, were studied. All were
      subjected to an upper gastrointestinal endoscopy, 24 h esophageal pH monitoring
      and a new manometric study. RESULTS: Eighty percent of patients had symptoms
      suggestive of gastroesophageal reflux, 31% had retrosternal pain and 25% had
      dysphagia. Upper endoscopy was normal in 41% and showed erosive esophagitis or
      Barrett esophagus in 27%. Fifty percent of patients had an abnormal acid reflux.
      There were no significant differences in manometric parameters between patients
      with and without acid reflux. CONCLUSIONS: Symptoms of gastroesophageal reflux
      not necessarily mean that a pathological reflux is present. Primary motor
      disorders of the esophagus may cause similar symptoms.

PMID- 15449552
TI  - [Clinical features of 32 patients with cutaneous small vessel vasculitis].
AB  - BACKGROUND: The skin is a common target of small vessel vasculitis, with a wide
      assortment of pathological changes. This condition is usually associated to
      systemic diseases. AIM: To report the clinical and pathological features of
      patients with cutaneous small vessel vasculitis. MATERIAL AND METHODS: A
      retrospective review of 32 patients with a pathological diagnosis of cutaneous
      vasculitis. RESULTS: Seventy two percent of patients were women. Cutaneous
      lesions were mainly located in the lower limbs (94%). The most common lesion was
      palpable purpura (62%). Connective tissue diseases and systemic vasculitis were
      the most commonly associated systemic diseases. CONCLUSIONS: Palpable purpura is
      the most common manifestation of cutaneous small vessel vasculitis, that is
      usually associated to connective tissue diseases or systemic vasculitis.

PMID- 15449553
TI  - [Smoking habit in school age children, in Chile].
AB  - BACKGROUND: In Chile, there is no information about the prevalence of smoking
      among basic and high school students. AIM: To study the prevalence of smoking
      among school age population. MATERAL AND METHODS: A cross sectional survey was
      conducted during 2001, assessing tobacco use and smoking habit in a
      representative sample of 15,119 randomly selected students. RESULTS: Sixty four
      percent of students had smoked at least once in their lifetime. Eighteen percent
      of students smoked daily and 15%, occasionally. The figures for women were higher
      (19 and 18% respectively). The mean age for the first contact with smoking was
      12.3 years and, for starting the smoking habit, 13.2 years. Smokers increased the
      amount of cigarettes during weekends. Higher prevalence rates of smoking were
      observed in students from the Southern region of the country and of lower
      socioeconomic levels. From the 3rd grade on, there is an increased risk of having
      contact with tobacco and smoking for the first time and from 6th grade on, this
      risk becomes permanent. The adjusted Odds Ratio to be a smoker is significantly
      higher when the mother is a current or irregular smoker (OR 1.9 95 CI; 1.7-2.0).
      CONCLUSIONS: High smoking prevalence rates were detected in this survey, mainly
      in women. The risk for smoking starts early during school life. Therefore, health
      promotion programs must include elementary and high school students.

PMID- 15449554
TI  - [Management of gallbladder cancer with invasion of the muscular layer].
AB  - BACKGROUND: Gallbladder cancer is the leading cause of death of cancer among
      women in Chile. Detection of early forms of the disease during the pathological
      study of the cholecystectomy specimen is common. The management of these cases,
      specially those with invasion of the muscular layer is under discussion. AIM: To
      analyze the clinical features of patients with gallbladder cancer and muscular
      layer invasion and their prognosis after a simple cholecystectomy. PATIENTS AND
      METHODS: We studied a series of 46 patients with gallbladder cancer and invasion
      of the muscular layer. In the majority of cases diagnosis was performed at the
      moment of specimen study. Eleven patients underwent reoperation. Of these, ten
      underwent lymphadenectomy and liver resection while one patient underwent
      resection of the cystic duct stump. RESULTS: During follow up, five patients died
      as a consequence of gallbladder cancer. Overall survival was 78%, with no
      differences between patients subjected or not a new operation. CONCLUSIONS:
      Gallbladder cancer with muscular infiltration has a good prognosis, independent
      of the type of therapy.

PMID- 15449555
TI  - [Laparoscopic splenectomy in hematological diseases].
AB  - BACKGROUND: Idiopathic thrombocytopenic purpura (ITP) is the most common
      indication for elective splenectomy. The laparoscopic approach has been used over
      the past ten years. AIM: To report our experience with laparoscopic splenectomy.
      PATIENTS AND METHODS: Retrospective review of 27 patients subjected to
      splenectomy due to hematological diseases. Among them, 17 patients (78% female,
      age range 17-70 years old) were subjected to a laparoscopic splenectomy.
      Eligibility criteria were the presence of benign disease, an informed consent by
      the patient, a spleen size of less than 20 cm by ultrasound and absence of
      previous surgery in the upper left quadrant. The rest of the patients were
      subjected to an open splenectomy. RESULTS: Seventy one percent of patients
      subjected to laparoscopic splenectomy had an ITP. Mean operating time was 184
      minutes. The mean spleen size was 11 cm and the mean weight was 186 g (70-450).
      No patient died or had complications. No patient required a conversion to an open
      surgery. Transfusions were not required. The median hospital stay was 3 days.
      CONCLUSIONS: Elective laparoscopic splenectomy is a safe and low risk surgical
      procedure.

PMID- 15449556
TI  - [Methotrexate use in patients with systemic lupus erythematosus].
AB  - BACKGROUND: In the past ten years, methotrexate (MTX) has appeared as an
      alternative for the treatment of systemic lupus erythematosus (SLE). AIM: To
      evaluate the use of MTX and the results of treatment in a group of patients with
      SLE. PATIENTS AND METHODS: Retrospective review of 426 files of patients with
      SLE. Of these, all patients treated with MTX were selected. A review protocol was
      designed, stating sex, age, time of disease evolution, previous treatment, MTX
      prescription, doses, effectiveness and side effects. RESULTS: Seven patients were
      selected. All were women, with an age range of 26 to 62 years old and with 5 to
      34 years of disease evolution. Previous treatment with non steroidal anti
      inflammatory drugs, steroids, hydroxychloroquine and azathioprine ranged from 6
      to 631 months (average=147.3). Persistent joint and/or skin manifestations were
      the main cause for the use of MTX. The dose ranged from 75 to 15 mg and the
      treatment lapse from 6 to 106 months. It was effective in all patients, allowing
      a reduction in prednisone doses. Two patients experienced a rise in serum
      transaminases and one had gastric intolerance, that required treatment
      discontinuation. CONCLUSIONS: MTX is rarely used in SLE. Its main prescription
      and effectiveness is in joint and skin manifestations, allowing to decrease
      steroid doses. However, side effects are frequent.

PMID- 15449557
TI  - [Determination of a BRCA1 gene mutation in a family with hereditary breast
      cancer].
AB  - BACKGROUND: Breast cancer is the main cause of death among women between 40 and
      55 years old, in whom the hereditary cases are common. Therefore, the molecular
      diagnosis of germ line mutations involved in breast cancer susceptibility is
      relevant. BRCA1 and BRCA2 have been described as the two major genes involved in
      familial breast/ovarian cancer. We are performing a screening of BRCA1 and BRCA2
      genes, in a group of 50 high risk Chilean families for breast/ovarian cancer. We
      have detected a mutation, 3936 C>T, that leads to a truncated protein, in two
      affected women from one of the families in study. AIM: To report the results of
      the screening for 3936 C>T in healthy relatives of index women. MATERIAL AND
      METHODS: The molecular diagnosis of this mutation was offered to the healthy
      members of this family, and 17 relatives accepted to be tested. The region of the
      BRCA1 gene that includes the 3936 C>T mutation, was analyzed through PCR
      amplification, digestion with restriction enzyme BstNI, and direct sequencing.
      RESULTS: 3936 C>T DNA mutation was present in 8 relatives. CONCLUSIONS:
      Considering the high risk of having a mutation in the BRCA1 gene, specially in
      pre-menopausal women, the molecular diagnosis, genetic and clinical counseling
      are highly relevant. In Chile the molecular diagnosis is still not widely
      applied.

PMID- 15449558
TI  - [Clinical, cytogenetic and molecular characterization of a new case of Nijmegen
      breakage syndrome in Chile].
AB  - The Nijmegen Breakage Syndrome (NBS) is a rare autosomal recessive disorder
      associated with microcephaly, immunodeficiency, chromosome instability and cancer
      proneness. The mutated gene that results in NBS codes for nibrin (Nbs1/p95), a
      DNA repair protein that is functionally linked to ATM, the kinase protein product
      of the gene responsible of ataxia-telangiectasia (A-T). We report the clinical,
      cytogenetic and molecular characterization of a second case of NBS in Chile
      detected by us. The patient is a 7 year old Chilean boy from a consanguineous
      marriage, with microcephaly, immunodeficiency and acute non lymphocytic leukemia
      (ANLL). As NBS shares chromosomal and cellular features with A-T, the cytogenetic
      studies of this patient also included 3 A-T patients. Our results showed that the
      frequency of spontaneous and X rays induced chromosomal aberrations in NBS are
      higher than in A-T cells. DNA analysis revealed that the patient is homozygous
      for the Slavic mutation 657del5 in the NBS1 gene. This finding and the absence of
      nibrin in patient's cells, confirmed the clinical diagnosis of NBS in our
      patient.

PMID- 15449559
TI  - [Acute suppurative thyroiditis. Report of a pediatric case].
AB  - Acute suppurative thyroiditis (AST) is an uncommon condition because thyroid
      gland is remarkably resistant to infections. In children, anatomic defects such
      as a left pyriform sinus fistula or a thyroglossal duct remnant predispose to
      this infection. Once the diagnosis is confirmed by ultrasound or computed
      tomography, antimicrobial therapy based on the culture and Gram staining must be
      started. After two or three weeks of treatment, predisposing anatomic defects
      must be sought cautiously. We report a 13 year old girl presenting with cervical
      pain and fever. A cervical ultrasound showed an enlarged thyroid lobule with
      hypoecogenic zones that suggested a supurative collection. Cefotaxime and
      cloxacillin were started. A needle aspiration of the collection obtained a
      purulent material. The culture of this material yielded a Streptococcus
      Pneumoniae. The clinical condition of the patient improved and she was discharged
      in good conditions. Two months later a contrast esophagus X ray did not show
      predisposing anatomic defects.

PMID- 15449560
TI  - [A national survey on smoking habit among health care workers in Chile].
AB  - BACKGROUND: Worldwide, smoking is the main avoidable cause of death among adults.
      AIM: To study smoking habits among health care workers in Chile. MATERIAL AND
      METHODS: A national survey about smoking among subjects working in the Chilean
      Ministry of Health. An anonymous and self administered enquiry was used. RESULTS:
      The enquiry was answered by 20,848 employees, corresponding to 58% of the total
      universe of workers. There was an overall prevalence of smoking of 40.7%. Sixty
      four percent of smokers did it daily and their mean consumption was 7 cigarettes
      per day. Smoking was more common among men than women (43 and 39.6%,
      respectively). Also, nicotine addiction was also more common among men (16.5 and
      11.7%, respectively). The prevalence of smoking decreased along with age.
      Journalists, guards, students and paramedics had the higher prevalence of
      smoking. Physicians, teachers and nutritionists had the lower prevalence.
      Although physicians had the lower frequency of smoking, they had the higher
      prevalence of nicotine addiction. Forty five percent of smokers were interested
      in therapies to quit, 69% did not allow smoking at home and 89% agreed with
      smoking restrictions in work places. CONCLUSIONS: The prevalence of smoking among
      health care workers is similar to that of the general population in Chile.

PMID- 15449561
TI  - [Jellyfish sting. An update].
AB  - Jellyfish are aquatic organisms, whose number increases under certain conditions
      of water temperature. They can sting humans, which can be fatal. The liberation
      of structures known as nematocysts induces the extrusion of the poison, to attack
      their victims. The poison produces characteristic local and systemic reactions.
      Since an increased number of these organisms has been detected in our coastline,
      we review the epidemiology, symptoms and diagnosis of the syndrome produced by
      the bite, to improve its management.

PMID- 15449562
TI  - [Bioethics and psychotherapy: which moral assumptions sustain psychotherapeutical
      acts?].
AB  - BACKGROUND: Since about 1970 biomedical ethics crystallized into a full-fledged
      discipline. The so called "ethical turn" is a fundamental conceptual challenge
      for the field of medicine and has generated heated controversy. Today, the
      ancient psychotherapeutic framework is under the severest strain in its long
      history. AIM: To review the relationship between psychotherapy and the conceptual
      shift in moral theory. MATERIAL AND METHOD: To forge a new model for the patient
      physician relationship, speech acts and nature of man derived from a "pragmatic
      turn" of bioethics. RESULTS: Research findings suggest that behavior, cognitive
      and psychodynamic psychotherapies are speech-acts constituted by a hierarchy of
      subordinate acts distributed on three levels: the level of the locutionary act,
      the act of saying; the level of the illocutionary act (or force), what we do in
      saying and the level of the perlocutionary act, what we provoke by the fact that
      we speak. CONCLUSIONS: Advances in linguistic research have led to a more
      sophisticated understanding of how psychotherapy affects ethical issues. These
      developments point towards a new era of psychotherapeutical theory and practice
      in which specific modes of psychotherapy can be designed to target specific
      dilemmas of medical ethics.

PMID- 15449563
TI  - [Search strategies in evidence-based medicine].

PMID- 15449564
TI  - [Einthoven: the man and his invention].
AB  - Einthoven, a Dutch physician, was awarded the Nobel Prize for Physiology or
      Medicine for his discovery of the mechanism of the electrocardiogram. He was born
      on May 21, 1860, in Semarang, on the island of Java. In 1878 entered the
      University of Utrecht in The Netherlands, as a medical student, where he also
      became a keen sportsman. In 1885, he was appointed Professor of Physiology at the
      University of Leiden, where he began to work using first a capillary
      electrometer. Later, Einthoven invented a new galvanometer to generate
      electrocardiograms using a fine quartz string coated in silver and published his
      findings in 1901 and 1903. Einthoven is remembered by most of his colleagues and
      clinical peers as a very modest person who was hospitable and honest. He died at
      the age of sixty seven.

PMID- 15449565
TI  - [Physicians and the hospitality of pharmaceutical companies].

PMID- 15449566
TI  - Assessment of the longitudinal changes in bone mineral density in patients
      receiving home parenteral nutrition.
AB  - BACKGROUND: Low bone mineral density (BMD) is commonly reported in patients
      receiving home parenteral nutrition (HPN), but it remains unclear whether or not
      an accelerated bone loss occurs during HPN therapy. We evaluated the spinal, hip,
      and forearm bone mass density longitudinally in a cohort of 75 patients receiving
      HPN. METHODS: A total of 943 regional dual-energy x-ray absorptiometry scans, 335
      spinal, 318 hip, and 290 forearm, obtained between 1995 and 2003 in 75 patients
      receiving HPN, were used for the analysis of the annual changes in BMD. The
      average (SD) number of scans per patients was 4.4 (2.9), and follow-up time was
      4.1 (1.9) years. Diagnoses were Crohn's disease (n = 35) and other conditions
      (non-Crohn's diseases; n = 40). Data were analyzed using a linear random
      coefficient model. RESULTS: There was a statistically significant overall decline
      over time in spinal, hip, and forearm BMD, corresponding roughly to a 1% annual
      loss (p < .005); however, the loss was not significantly larger than that of age
      and sex-matched healthy subjects. In Crohn's disease patients, model estimates of
      spinal and hip BMD on the initiation of HPN therapy were significantly reduced
      compared with normal, whereas values were not significantly reduced in non
      Crohn's disease patients. CONCLUSIONS: With the current protocols for HPN
      treatment, the annual decline in BMD is moderate and not significantly larger
      than in age- and sex-matched healthy subjects. A considerable part of the
      metabolic bone disease in these patients is related to the underlying disease for
      which the HPN was indicated.

PMID- 15449567
TI  - Early enteral feedings in adults receiving venovenous extracorporeal membrane
      oxygenation.
AB  - INTRODUCTION: For over 20 years extracorporeal membrane oxygenation (ECMO) has
      been an advanced treatment for adults, children and neonates with severe
      respiratory failure that has failed to respond or improve with conventional
      therapy. Withholding enteral feeding in patients on ECMO is common practice in
      many centers, based partly on the risk of splanchnic ischemia resulting in loss
      of intestinal integrity, predisposing to bacterial translocation and sepsis. We
      report one center's experience with early enteral nutrition in adult patients
      receiving venovenous (VV) ECMO for severe respiratory failure. METHODS: Adult
      patients that received VV ECMO at LSUHSC-Shreveport over the last 8 years were
      eligible for inclusion. RESULTS: A total of 27 patients met these criteria and
      their charts and nutrition therapy reviewed. Average duration of ECMO support was
      8.7 +/- 3.6 days. Twenty-six of 27 (96%) received enteral nutrition via gastric
      tube alone or in combination with total parenteral nutrition (TPN). Eighteen
      patients received enteral nutrition as their only source of nutritional
      supplementation, with the remainder receiving partial nutrition support via the
      parenteral route. Seventy-five percent of the patients received prokinetic
      medication within the first 24 hours, with 95% receiving prokinetic therapy by 48
      hours. No patients developed intestinal ischemia, gastrointestinal bleeding, or
      other complications related to early enteral feeding. CONCLUSION: Enteral
      nutrition started within the first 24 to 36 hours of initiating venovenous ECMO
      support is safe and well-tolerated in adults. No serious adverse events were
      attributable to enteral nutrition in these patients.

PMID- 15449568
TI  - Effect of enteral nutrition of monoacetoacetin on bacterial translocation in
      burned rats.
AB  - BACKGROUND: Bacterial translocation (BT) occurs under stress, and enteral
      nutrition is said to be effective in counteracting this effect. The usefulness of
      i.v. nutrition of monoacetoacetine (MA) under stress has been reported
      previously, and we studied the effect of enteral nutrition of MA as it is related
      to BT. METHODS: Rats were given 13.6% MA or 15% glucose (Glu) via gastrostomy,
      and after 4 days a 30% full-thickness burn was made. Before and after
      administration of the burn, we measured serum cytokines; amounts of bacteria in
      the mesenteric lymph node (MLN), liver, and spleen (estimation of BT); mucosal
      thickness of the terminal ileum; and body weight changes. To confirm the
      effectiveness of MA in the small intestine, we estimated succinyl-CoA:3-oxoacid
      CoA-transferase (SCOT) expression in the terminal ileum by immunohistochemical
      staining and Western blot analysis. RESULTS: At 6 hours after burn, all cytokines
      were lower, and BT in the MLN was inhibited significantly in the MA group. Ileal
      mucosal thickness was not significantly different, but mucosa was more edematous
      in the Glu group. At 3 days after burn injury, BT was significantly inhibited in
      the MLN and liver, and the ileal mucosa was significantly thicker in the MA
      group. Body weight loss after burn injury was significantly smaller in the MA
      group. SCOT expression was the strongest at 6 hours after burn injury by Western
      blot analysis but not by immunohistochemical staining. CONCLUSIONS: Enteral
      nutrition of MA may be useful for the inhibition of intestinal mucosal atrophy
      and the prevention of multiple organ dysfunction syndrome caused by the
      inhibition of BT and subsequent overproduction of cytokines.

PMID- 15449569
TI  - Inhibition of 5-lipoxygenase induces cell death in anti-inflammatory fatty acid
      treated HL-60 cells.
AB  - BACKGROUND: Enteral nutrition containing eicosapentaenoic (20:5 omega-3) and
      gamma-linolenic acid (18:3 omega-6) decreases leukotriene B4 levels and
      neutrophils in bronchoalveolar lavage fluid of patients and animals with acute
      respiratory distress syndrome. Reduction in pulmonary inflammation may be caused
      by decreased neutrophil migration or survival. We showed that apoptosis increases
      in eicosapentaenoic/gamma-linolenic acid-treated HL-60 cells. We hypothesize that
      eicosapentaenoic/gamma-linolenic acid-induced apoptosis involves downstream
      metabolic products of lipoxygenase and cyclooxygenase enzymes. This study
      determined the effects of inhibitors of lipoxygenase and cyclooxygenase enzymes
      on eicosapentaenoic/gamma-linolenic acid-treated HL-60 cells. METHODS: Cells were
      incubated with 50 microM eicosapentaenoic/20 microM gamma-linolenic acid in the
      presence of an enzyme inhibitor (1-10 microM) for 12 hours. Compounds were used
      to inhibit cyclooxygenase (ibuprofen), 12-lipoxygenase (baicalein), or 5
      lipoxygenase (AA-861). Flow cytometry assessed viability, apoptosis, and
      necrosis. RESULTS: 5-Lipoxygenase inhibition decreased cell viability and
      increased cell death (apoptosis + necrosis) in eicosapentaenoic/gamma-linolenic
      acid-treated HL-60 cells. Inhibition of cyclooxygenase 1 and 2 and 12
      lipoxygenase had no significant effect on cellular viability and death in
      eicosapentaenoic/gamma-linolenic acid-treated HL-60 cells. Adding leukotriene B4
      counteracted the effect of 5-lipoxygenase inhibition on apoptosis in
      eicosapentaenoic/gamma-linolenic acid-treated HL-60 cells. CONCLUSIONS: These
      data suggest that the processing of eicosapentaenoic and gamma-linolenic acid by
      5-lipoxygenase is critical to HL-60 cell survival.

PMID- 15449570
TI  - Orotic aciduria and plasma urea cycle-related amino acid alterations in short
      bowel syndrome, evoked by an arginine-free diet.
AB  - BACKGROUND: The small bowel is believed to play a crucial role in endogenous
      arginine synthesis. Therefore, an insufficient arginine supply in the situation
      of massive intestinal resection might impede normal arginine metabolism. This
      study sought to determine the clinical and metabolic effects of an arginine-free
      diet in stable short-bowel patients. METHODS: Four patients, mean age 49 years
      (range: 26-67), mean time from intestinal resection 46 m (range: 15-97), and
      remnant small bowel of 30 to 100 cm consumed an L-amino acid arginine-free diet
      (egg pattern) for 5 days (0.9 g protein equivalent/kg/d plus malabsorption
      adjustments). Fasting plasma amino acids, ammonium, and blood chemistries were
      assessed at days 0, 3, and 5. Urinary orotate, orotidine, uric acid, urea,
      creatinine, and total nitrogen were evaluated daily. RESULTS: Significant
      decreases in plasma levels of arginine, ornithine, and hydroxyproline occurred at
      day 5. A decreasing trend in plasma citrulline and a significant plasma glutamine
      increase were also observed in the same period. Conversely, ammonium
      concentrations remained normal. Regarding urine compounds, striking orotic
      aciduria with a peak at day 4 (14-fold vs baseline) and significant decreases in
      uric acid and urea excretion were found. There were no relevant clinical events.
      CONCLUSIONS: Despite the limited number of patients in our work and their
      relative heterogeneity, our results support the idea of the indispensability of
      an exogenous arginine supply in humans under short bowel syndrome conditions.
      Studies in larger series are needed to further investigate these findings.

PMID- 15449571
TI  - Feasibility and safety of needle catheter jejunostomy for enteral nutrition in
      surgically treated severe acute pancreatitis.
AB  - BACKGROUND: The role of the gut in the development of septic complications and
      promising clinical results have led to a shift from the parenteral to the enteral
      route for nutrition support of patients with acute pancreatitis. In patients
      undergoing surgery for severe necrotizing pancreatitis, the application of a
      needle catheter jejunostomy might be useful. However, there is a shortage of
      clinical data on its feasibility and possible harmful effect. METHODS: Between
      January 1999 and December 2002, 13 patients were operated for severe acute
      necrotizing pancreatitis. At the time of surgery, needle catheter jejunostomy was
      performed using a standard technique. Enteral nutrition was initiated without a
      strict protocol by feeding small amounts of a standard diet and carefully
      monitoring patient tolerance. As long as necessary, patients were also fed
      parenterally in order to achieve target caloric goals. RESULTS: No major tube- or
      feeding-related complications were observed. A single case of tube dislodgement
      caused by manipulation during relaparotomy for lavage occurred and was rectified
      during the same operation. CONCLUSIONS: In patients undergoing surgery for severe
      acute pancreatitis, needle catheter jejunostomy for long-term enteral nutrition
      can be applied with no additional risk.

PMID- 15449572
TI  - Technical considerations for fan-beam dual-energy x-ray absorptiometry body
      composition measurements in pediatric studies.
AB  - BACKGROUND: A piglet model was used to determine the influence of frequently
      encountered situations in clinical studies of infants and young children on fan
      beam dual-energy x-ray absorptiometry (DXA) measurements. METHODS: DXA scans of
      piglets (640 g to 21,100 g) were acquired in the infant and adult mode and were
      analyzed with 1 infant, 1 pediatric, and 3 versions of adult software. RESULTS:
      The effect of repositioning of the piglets from the center to the periphery of
      the scanning table on DXA measurements included an average difference of up to
      0.5% for total weight, 5.0% for bone mineral content, 5.6% for bone mineral
      density, 1.3% for lean mass, and 21.9% for fat mass (< or = .05, all comparisons)
      although no significant changes occurred when the piglets were scanned in
      symmetrical positions on either edge of the scanning table. Different posture
      (prone vs supine and side), varied number of blankets overlaid or wrapped around
      the piglet, and parenteral but not enteral bolus feeding could significantly
      alter fan-beam DXA measurements to varying extents. Adult and pediatric software
      underestimated bone area and bone mineral content but overestimated bone mineral
      density, lean mass, fat mass, and total weight compared with infant software
      measurements. However, strong predictive relationships among these fan-beam DXA
      data in subjects >10 kg allow systematic corrections of data from different scan
      modes and different software. CONCLUSIONS: Attention to details and consistency
      in the technique for scan acquisition and analysis are critical to the generation
      of meaningful data and to allow for detection of true differences in DXA
      measurements of small subjects.

PMID- 15449573
TI  - Enteral nutrition and cardiovascular medications in the pediatric intensive care
      unit.
AB  - BACKGROUND: Enteral nutrition has multiple benefits for critically ill patients.
      However, the administration of enteral nutrition to patients requiring
      medications for cardiovascular support is controversial secondary to concerns of
      altered splanchnic perfusion. The objective of this study is to evaluate the
      tolerance of enteral nutrition in pediatric patients receiving cardiovascular
      medications. METHODS: This was a retrospective chart review of patients admitted
      to the pediatric intensive care unit at Children's Healthcare of Atlanta at
      Egleston in a 1-year period. Patients were eligible for the study if they
      received enteral nutrition during or within 24 hours of requiring continuous
      infusion of dopamine, dobutamine, epinephrine, norepinephrine, or neosynephrine.
      RESULTS: Fifty-five admissions (52 patients) met study criteria. Patients ranged
      in age from 1 month to 20 years old. Although a large number (71%) of patients
      experienced at least 1 feeding interruption, the majority (70%) of reasons cited
      for stopping or slowing feedings were not related to gastrointestinal (GI)
      tolerance. Only 29% of patients had feedings held for perceived intolerance.
      Vomiting was the most often-cited reason for these interruptions. Constipation
      was reported in 36% of patients but cited only 4 times as a reason for feeding
      interruption. Four patients exhibited evidence of GI bleeding. This bleeding was
      considered clinically insignificant in 2 patients and appeared unrelated to
      enteral feedings in the others. CONCLUSIONS: This study suggests that many
      pediatric patients receiving cardiovascular medications tolerate enteral
      nutrition without adverse events. Further prospective studies are needed to
      determine whether enteral nutrition can consistently benefit these critically ill
      pediatric patients.

PMID- 15449574
TI  - Selenium concentrations in pancreatic juice of patients with chronic
      pancreatitis.
AB  - BACKGROUND: Free radicals have been implicated as an important mediator in the
      pathogenesis of tissue injury. Experimental animal models would suggest selenium
      deficiency contributes to the pathogenesis of chronic pancreatitis (CP). In
      clinical studies, low plasma selenium levels have been reported in patients with
      CP. To the best of our knowledge, selenium levels have not been measured in
      pancreatic juice. METHODS: Twenty-seven patients with chronic intermittent upper
      quadrant abdominal pain were studied. The diagnosis of CP was made by endoscopic
      retrograde cholangiopancreatography. Patients were allowed to eat an ad libitum
      western diet. None of the patients was taking selenium supplements. Patients
      underwent upper endoscopy with routine conscious sedation. Secretin (0.2
      microg/kg) was given i.v. immediately before intubation. Pancreatic juice
      collected from the duodenum was immediately frozen in liquid nitrogen and stored
      at -80 degrees C until the assay was performed. Selenium levels of the pancreatic
      juice were determined using the inductively coupled plasma-mass spectrometry
      method. RESULTS: Twelve patients had an abnormal pancreatogram. The gender and
      median age in controls and CP were 11 females and 4 males (54 years, range 32-78)
      and 7 females and 5 males (56 years, range 37-79), respectively. The etiology of
      CP was alcohol and idiopathic. The median selenium concentration in controls was
      4 microg/mL (range, 2-11.5) and in CP 4.5 microg/mL (range, 2-16). There was not
      a statistically significant difference between the 2 groups (p = not
      significant). CONCLUSIONS: The pancreatic juice concentration of selenium is
      similar in patients with CP compared with age matched controls. Our results would
      therefore suggest that the effects of selenium on pancreatic injury might be
      systemic rather than local tissue effect.

PMID- 15449575
TI  - Cholesterol oxidation in intravenous lipid emulsions: safety of preparations
      before and after experimental hyperoxia.
AB  - The aim of this preliminary study was to assess the possible presence of
      cholesterol oxidation products in 2 i.v. lipidic emulsions with different fatty
      acid compositions (long-chain triglyceride, medium-chain triglyceride-long-chain
      triglyceride). Because these emulsions are currently used in neonatal parenteral
      nutrition, their direct venous introduction might be potentially dangerous
      because of the possible atherogenic role of cholesterol oxidation products. The
      emulsions were analyzed when bottles were opened (ie, under normal condition of
      administration) and after a 12-hour direct experimental exposure to air and high
      (90%) oxygen concentrations. 7-Ketocholesterol and 5alpha-epoxycholesterol were
      chosen as markers of cholesterol oxidation and detected by gas chromatography
      mass spectrometry of their trimethylsilyl ethers. The detected amounts were
      always very low and in some cases below the detection limit of the analytical
      method for the 2 cholesterol oxidation products (COPs; 0.1 and 0.3 microg/g of
      extracted lipids). Immediately after opening the bottles, their concentrations
      were lower in the emulsions containing the higher amounts of polyunsaturated
      fatty acids. Experimental hyperoxic exposure generally determined only a mild
      increase in the content of cholesterol oxidation biomarker, and after exposure to
      oxygen, the amounts of COPs were slightly higher than after exposure to air. The
      results of the present study are undoubtedly reassuring for the safety of
      neonates, although caution is always required when drawing conclusions from in
      vitro data.

PMID- 15449576
TI  - Effects of a nutritional supplement on the immune response and cytokine
      production in free-living Chilean elderly.
AB  - BACKGROUND: Immune response is impaired in the elderly. Our aim was to study the
      effects of a special nutritional formula on the immune response and response to
      influenza and pneumococcal vaccination in elderly subjects. METHODS: Sixty
      healthy subjects aged > or = 70 years, with a Mini Mental score > or = 22 were
      studied. Half of the subjects received a special nutritional formula (in addition
      to the regular diet) providing, among other nutrients, 480 kcal, 31 g proteins,
      120 IU vitamin E, 3.8 microg vitamin B12, 400 microg folic acid, 10(9) cfu
      Lactobacillus paracasei (NCC 2461), and 6 g of fructo-oligosaccharides. At 4
      months of follow-up, subjects were vaccinated against influenza and pneumococcus.
      Lymphokine production by mononuclear cells (PBMC), lymphocyte subpopulations, and
      natural killer cell (NK) activity were measured at baseline and 4 months of
      follow-up (before vaccination). Antibodies against influenza and pneumococcal
      antigens and flu-stimulated production of interferon gamma and interleukin-2 by
      PBMC were measured at 4 and 6 months. Skin response to 7 recall antigens and body
      composition were assessed at baseline and at 4 and 12 months. All infections
      occurring during the study period were recorded. RESULTS: NK activity increased
      in supplemented subjects and decreased in nonsupplemented individuals.
      Interleukin-2 production by PBMC and the proportion of T cells with NK activity
      decreased in controls and did not change in supplemented subjects. Supplemented
      subjects reported less infections than nonsupplemented individuals (in 13% and
      22% of scheduled visits, respectively; p = .02). CONCLUSIONS: This nutritional
      supplement increased innate immunity and protection against infections in elderly
      people.

PMID- 15449577
TI  - Dexamethasone plus glucagon-like peptide 2 given to lactating rat dams has a late
      effect on intestinal lipid uptake in the weanling offspring.
AB  - BACKGROUND: Glucagon-like peptide 2 (GLP-2) has a trophic effect on the intestine
      and enhances intestinal absorption in adult animals, but its effect in young rats
      is unknown. Glucocorticosteroids accelerate the ontogeny of the intestine, and in
      adult animals they increase the uptake of sugars and lipids. We hypothesized that
      GLP-2 and dexamethasone (DEX), when administrated to lactating rat dams, will
      enhance lipid uptake in the suckling and weanling offspring. METHODS: Eight
      nursing rats were treated during lactation, 19 to 21 days, with GLP-2 (0.1
      microg/g/d subcutaneously [s.c.]), DEX (0.128 microg/g/d s.c.), GLP-2 + DEX (GLP
      2 0.1 microg/g/d s.c. plus DEX 0.128 microg/g/d s.c.), or placebo. Half of the
      offspring ("sucklings") were killed at 19 to 21 days of age, and half were killed
      4 weeks later ("weanlings"). The rate of intestinal uptake of fatty acids (12:0,
      lauric; 16:0, palmitic; 18:0, stearic; 18:1, oleic; 18:2, linoleic; and 18:3,
      linolenic) and cholesterol were assessed using an in vitro ring technique.
      RESULTS: GLP-2 and DEX resulted in loss of body weight in sucklings, which was
      prevented by giving the combination GLP-2 + DEX. The jejunal atrophy in sucklings
      given DEX was prevented by giving GLP-2 + DEX, but GLP-2 + DEX did not prevent
      the decline in jejunal and ileal villous height and crypt depth observed in
      weanlings given DEX. GLP-2 had little effect on lipid uptake in sucklings,
      whereas DEX or GLP-2 + DEX increased the uptake of lipids. In contrast, in
      weanlings there was malabsorption of several lipids with GLP-2 or GLP-2 + DEX,
      but not with DEX. Lipid uptake was lower in weanlings than in sucklings, and this
      age-associated decline was not altered by GLP-2 or DEX. CONCLUSIONS: The loss of
      body weight and the jejunal atrophy induced by DEX in sucklings is prevented by
      adding GLP-2. Giving DEX or GLP-2 + DEX to lactating mothers enhances lipid
      uptake in their suckling offspring. In marked contrast, a month after lactating
      dams were given GLP-2 or GLP-2 + DEX, there was reduced lipid absorption in the
      postweaning animals. Thus, giving GLP-2 + DEX during lactation may be useful to
      enhance lipid uptake in the suckling offspring, without adverse effects on body
      weight or intestinal characteristics. However, the late effects of this treatment
      on lipid absorption were of concern, and could be potentially deleterious to the
      nutritional well-being of the animal.

PMID- 15449578
TI  - The glucose transporter families SGLT and GLUT: molecular basis of normal and
      aberrant function.
AB  - Glucose enters eucaryotic cells via 2 different types of membrane associated
      carrier proteins, the Na+-coupled glucose transporters (SGLT) and glucose
      transporter facilitators (GLUT). Three members of the SGLT family function as
      sugar transporters (SGLT1 and SGLT2) or sensors (SGLT3). The human GLUT family
      consists of 14 members, of which 11 have been shown to catalyze sugar transport.
      The individual isotypes exhibit different substrate specificity, kinetic
      characteristics, and expression profiles, thereby allowing a tissue-specific
      adaptation of glucose uptake through regulation of their gene expression.
      Furthermore, some transporters (eg, GLUT4 and GLUT8) are regulated by their
      subcellular distribution. In addition to catalyzing glucose entry into cells,
      some isotypes (eg, GLUT2) seem to be involved in the mechanisms of glucosensing
      of pancreatic beta-cells, neuronal, or other cells, thereby playing a major role
      in the hormonal and neural control. Targeted disruption in mice has helped to
      elucidate the physiologic function of some isotypes (GLUT1, GLUT2, GLUT4).
      Furthermore, several congenital defects of sugar metabolism are caused by
      aberrant transporter genes (eg, the glucose-galactose malabsorption syndrome,
      SGLT1; the glucose transporter 1 deficiency syndrome; and the Fanconi-Bickel
      syndrome, GLUT2). In addition, a malfunction of glucose transporter expression or
      regulation (GLUT4) appears to contribute to the insulin resistance syndrome.

PMID- 15449579
TI  - Identification of humans using gait.
AB  - We propose a view-based approach to recognize humans from their gait. Two
      different image features have been considered: the width of the outer contour of
      the binarized silhouette of the walking person and the entire binary silhouette
      itself. To obtain the observation vector from the image features, we employ two
      different methods. In the first method, referred to as the indirect approach, the
      high-dimensional image feature is transformed to a lower dimensional space by
      generating what we call the frame to exemplar (FED) distance. The FED vector
      captures both structural and dynamic traits of each individual. For compact and
      effective gait representation and recognition, the gait information in the FED
      vector sequences is captured in a hidden Markov model (HMM). In the second
      method, referred to as the direct approach, we work with the feature vector
      directly (as opposed to computing the FED) and train an HMM. We estimate the HMM
      parameters (specifically the observation probability B) based on the distance
      between the exemplars and the image features. In this way, we avoid learning high
      dimensional probability density functions. The statistical nature of the HMM
      lends overall robustness to representation and recognition. The performance of
      the methods is illustrated using several databases.

PMID- 15449580
TI  - MAP estimation for hyperspectral image resolution enhancement using an auxiliary
      sensor.
AB  - This paper presents a novel maximum a posteriori estimator for enhancing the
      spatial resolution of an image using co-registered high spatial-resolution
      imagery from an auxiliary sensor. Here, we focus on the use of high-resolution
      panchomatic data to enhance hyperspectral imagery. However, the estimation
      framework developed allows for any number of spectral bands in the primary and
      auxiliary image. The proposed technique is suitable for applications where some
      correlation, either localized or global, exists between the auxiliary image and
      the image being enhanced. To exploit localized correlations, a spatially varying
      statistical model, based on vector quantization, is used. Another important
      aspect of the proposed algorithm is that it allows for the use of an accurate
      observation model relating the "true" scene with the low-resolutions
      observations. Experimental results with hyperspectral data derived from the
      airborne visible-infrared imaging spectrometer are presented to demonstrate the
      efficacy of the proposed estimator.

PMID- 15449581
TI  - Fundamental performance limits in image registration.
AB  - The task of image registration is fundamental in image processing. It often is a
      critical preprocessing step to many modern image processing and computer vision
      tasks, and many algorithms and techniques have been proposed to address the
      registration problem. Often, the performances of these techniques have been
      presented using a variety of relative measures comparing different estimators,
      leaving open the critical question of overall optimality. In this paper, we
      present the fundamental performance limits for the problem of image registration
      as derived from the Cramer-Rao inequality. We compare the experimental
      performance of several popular methods with respect to this performance bound,
      and explain the fundamental tradeoff between variance and bias inherent to the
      problem of image registration. In particular, we derive and explore the bias of
      the popular gradient-based estimator showing how widely used multiscale methods
      for improving performance can be explained with this bias expression. Finally, we
      present experimental simulations showing the general rule-of-thumb performance
      limits for gradient-based image registration techniques.

PMID- 15449582
TI  - Region filling and object removal by exemplar-based image inpainting.
AB  - A new algorithm is proposed for removing large objects from digital images. The
      challenge is to fill in the hole that is left behind in a visually plausible way.
      In the past, this problem has been addressed by two classes of algorithms: 1)
      "texture synthesis" algorithms for generating large image regions from sample
      textures and 2) "inpainting" techniques for filling in small image gaps. The
      former has been demonstrated for "textures"--repeating two-dimensional patterns
      with some stochasticity; the latter focus on linear "structures" which can be
      thought of as one-dimensional patterns, such as lines and object contours. This
      paper presents a novel and efficient algorithm that combines the advantages of
      these two approaches. We first note that exemplar-based texture synthesis
      contains the essential process required to replicate both texture and structure;
      the success of structure propagation, however, is highly dependent on the order
      in which the filling proceeds. We propose a best-first algorithm in which the
      confidence in the synthesized pixel values is propagated in a manner similar to
      the propagation of information in inpainting. The actual color values are
      computed using exemplar-based synthesis. In this paper, the simultaneous
      propagation of texture and structure information is achieved by a single,
      efficient algorithm. Computational efficiency is achieved by a block-based
      sampling process. A number of examples on real and synthetic images demonstrate
      the effectiveness of our algorithm in removing large occluding objects, as well
      as thin scratches. Robustness with respect to the shape of the manually selected
      target region is also demonstrated. Our results compare favorably to those
      obtained by existing techniques.

PMID- 15449583
TI  - Image restoration subject to a total variation constraint.
AB  - Total variation has proven to be a valuable concept in connection with the
      recovery of images featuring piecewise smooth components. So far, however, it has
      been used exclusively as an objective to be minimized under constraints. In this
      paper, we propose an alternative formulation in which total variation is used as
      a constraint in a general convex programming framework. This approach places no
      limitation on the incorporation of additional constraints in the restoration
      process and the resulting optimization problem can be solved efficiently via
      block-iterative methods. Image denoising and deconvolution applications are
      demonstrated.

PMID- 15449584
TI  - Iterative multimodel subimage binarization for handwritten character
      segmentation.
AB  - Existing binarization methods are categorized as either global or local. In this
      paper, we present a new category, where the image is considered a collection of
      subimages. Each subimage provides a statistical model for the handwritten
      characters that can be used to optimize the binarization of other subimages based
      on gray-level and stroke-run features. The proposed method uses these multimodels
      to iteratively arrive at the optimal threshold for each subimage. It can be
      applied to different types of documents where prior knowledge about the noisiness
      of the subimages is not available. Experimental results showed significant
      improvement in the binarization quality in comparison with other well-established
      algorithms.

PMID- 15449585
TI  - Efficient energies and algorithms for parametric snakes.
AB  - Parametric active contour models are one of the preferred approaches for image
      segmentation because of their computational efficiency and simplicity. However,
      they have a few drawbacks which limit their performance. In this paper, we
      identify some of these problems and propose efficient solutions to get around
      them. The widely-used gradient magnitude-based energy is parameter dependent; its
      use will negatively affect the parametrization of the curve and, consequently,
      its stiffness. Hence, we introduce a new edge-based energy that is independent of
      the parameterization. It is also more robust since it takes into account the
      gradient direction as well. We express this energy term as a surface integral,
      thus unifying it naturally with the region-based schemes. The unified framework
      enables the user to tune the image energy to the application at hand. We show
      that parametric snakes can guarantee low curvature curves, but only if they are
      described in the curvilinear abscissa. Since normal curve evolution do not ensure
      constant arc-length, we propose a new internal energy term that will force this
      configuration. The curve evolution can sometimes give rise to closed loops in the
      contour, which will adversely interfere with the optimization algorithm. We
      propose a curve evolution scheme that prevents this condition.

PMID- 15449586
TI  - Morse description and geometric encoding of digital elevation maps.
AB  - Two complementary geometric structures for the topographic representation of an
      image are developed in this work. The first one computes a description of the
      Morse-topological structure of the image, while the second one computes a
      simplified version of its drainage structure. The topographic significance of the
      Morse and drainage structures of digital elevation maps (DEMs) suggests that they
      can been used as the basis of an efficient encoding scheme. As an application, we
      combine this geometric representation with an interpolation algorithm and
      lossless data compression schemes to develop a compression scheme for DEMs. This
      algorithm achieves high compression while controlling the maximum error in the
      decoded elevation map, a property that is necessary for the majority of
      applications dealing with DEMs. We present the underlying theory and compression
      results for standard DEM data.

PMID- 15449587
TI  - Primary-consistent soft-decision color demosaicking for digital cameras (patent
      pending).
AB  - Color mosaic sampling schemes are widely used in digital cameras. Given the
      resolution of CCD sensor arrays, the image quality of digital cameras using
      mosaic sampling largely depends on the performance of the color demosaicking
      process. A common problem with existing color demosaicking algorithms is an
      inconsistency of sample interpolations in different primary color channels, which
      is the cause of the most objectionable color artifacts. To cure the problem, we
      propose a new primary-consistent soft-decision framework (PCSD) of color
      demosaicking. In the PCSD framework, we make multiple estimates of a missing
      color sample under different hypotheses on edge or texture directions. The
      estimates are made via a primary consistent interpolation, meaning that all three
      primary components of a color are interpolated in the same direction. The final
      estimate of a color sample is obtained by testing different interpolation
      hypotheses in the reconstructed full-resolution color image and selecting the
      best via an optimal statistical decision or inference process. A concrete color
      demosaicking method of the PCSD framework is presented. This new method
      eliminates certain types of color artifacts of existing color demosaicking
      methods. Extensive experimental results demonstrate that the PCSD approach can
      significantly improve the image quality of digital cameras in both subjective and
      objective measures. In some instances, our gain over the competing methods can be
      as much as 7 dB.

PMID- 15449588
TI  - Variable-branch tree-structured vector quantization.
AB  - Tree-structured vector quantizers (TSVQ) and their variants have recently been
      proposed. All trees used are fixed M-ary tree structured, such that the training
      samples in each node must be artificially divided into a fixed number of
      clusters. This paper proposes a variable-branch tree-structured vector quantizer
      (VBTSVQ) based on a genetic algorithm, which searches for the number of child
      nodes of each splitting node for optimal coding in VBTSVQ. Moreover, one
      disadvantage of TSVQ is that the searched codeword usually differs from the full
      searched codeword. Briefly, the searched codeword in TSVQ sometimes is not the
      closest codeword to the input vector. This paper proposes the multiclassification
      encoding method to select many classified components to represent each cluster,
      and the codeword encoded in the VBTSVQ is usually the same as that of the full
      search. VBTSVQ outperforms other TSVQs in the experiments presented here.

PMID- 15449589
TI  - Combining transcriptome data with genomic and cDNA sequence alignments to make
      confident functional assignments for Aspergillus nidulans genes.
AB  - Whole genome sequencing of several filamentous ascomycetes is complete or in
      progress; these species, such as Aspergillus nidulans, are relatives of
      Saccharomyces cerevisiae. However, their genomes are much larger and their gene
      structure more complex, with genes often containing multiple introns. Automated
      annotation programs can quickly identify open reading frames for hypothetical
      genes, many of which will be conserved across large evolutionary distances, but
      further information is required to confirm functional assignments. We describe a
      comparative and functional genomics approach using sequence alignments and gene
      expression data to predict the function of Aspergillus nidulans genes. By
      highlighting examples of discrepancies between the automated genome annotation
      and cDNA or EST sequencing, we demonstrate that the greater complexity of gene
      structure in filamentous fungi demands independent data on gene expression and
      the gene sequence be used to make confident functional assignments.

PMID- 15449590
TI  - Nucleotide composition in protein-coding and non-coding DNA in the zygomycete
      Phycomyces blakesleeanus.
AB  - The zygomycete Phycomyces blakesleeanus has a 30 Mb genome with a 35% content of
      guanine and cytosine (GC). We determined the GC content in Phycomyces genes and
      fragments of genes available in public databases, the frequency of nucleotides in
      each codon position, and the codon usage. We observed a difference of 18% between
      the GC content of protein-coding and non-coding DNA. This large difference
      allowed the visualization of protein-coding DNA by plotting the GC content along
      a segment of Phycomyces DNA. We have identified a high GC DNA segment linked to
      the pyrG genes of the zygomycete genera Phycomyces, Mucor, and Blakeslea that
      corresponds to the 3' end of the gene responsible for the protein kinase C.

PMID- 15449591
TI  - Multigene phylogeny reveals new lineage for Stachybotrys chartarum, the indoor
      air fungus.
AB  - Stachybotrys chartarum is an asexually reproducing fungus commonly isolated from
      soil and litter that is also known to occur in indoor environments and is
      implicated as the cause of serious illness and even death in humans. Despite its
      economic importance, higher level phylogenetic relationships of Stachybotrys have
      not been determined nor has a sexual state for S. chartarum been reported. DNA
      sequences from four nuclear and one mitochondrial gene were analyzed to determine
      the ordinal and familial placement of Stachybotrys within the Euascomycota. These
      data reveal that species of Stachybotrys including S. chartarum, S. albipes, for
      which the sexual state Melanopsamma pomiformis is reported, species of
      Myrothecium, and two other tropical hypocrealean species form a previously
      unknown monophyletic lineage within the Hypocreales. These results suggest that
      Stachybotrys and Myrothecium are closely related and share characteristics with
      other hypocrealean fungi. In addition, S. chartarum may have a sexual state in
      nature that consists of small, black, fleshy perithecia similar to Melanopsamma.

PMID- 15449592
TI  - Melanelixia and Melanohalea, two new genera segregated from Melanelia
      (Parmeliaceae) based on molecular and morphological data.
AB  - This paper continues a revision of generic concepts in the parmelioid lichens
      using molecular data in order to reach a consensus among lichenologists over
      which segregates proposed over the last two decades should be accepted. Here we
      employ data from three gene portions to provide a basis for a revised generic
      concept of the brown parmelioid lichens hitherto classified in Melanelia. The
      phylogeny was studied using a Bayesian analysis of a combined data set of nuclear
      ITS, LSU rDNA and mitochondrial SSU rDNA sequences. 173 new sequences were
      obtained from 38 specimens of 15 Melanelia species, 37 related parmelioid
      species, and eight non-parmelioid species. The results indicate that Melanelia is
      not monophyletic but falls into four different clades. The genus Melanelia is
      restricted here to a small group of saxicolous lichens related to the type
      species M. stygia, and with bifusiform conidia, while the remaining species, most
      of which are primarily corticolous and have mainly cylindrical to filiform
      conidia, belong to two other clades recognised as two new genera: Melanelixia and
      Melanohalea, to accommodate the M. exasperata and M. glabra groups, respectively.
      27 new combinations are made. The epicortex of Melanelixia species have pores or
      special structures termed here 'fenestrations', while most Melanohalea species
      are pseudocyphellate. Pleurosticta links to the Melanohalea clade but without
      strong support, and the phylogenetic position of M. disjuncta and its related
      species remains uncertain, linking with the Xanthoparmelia (syn. Neofuscelia)
      clade but also without strong support.

PMID- 15449593
TI  - Molecular phylogeny and biogeography of the widely distributed Amanita species,
      A. muscaria and A. pantherina.
AB  - The molecular phylogeny and biogeography of two widely distributed Amanita
      species, A. muscaria and A. pantherina, were studied based on specimens from
      diverse localities. Analyses of both a partial sequence of the ITS region of
      nuclear DNA and a partial sequence of the beta-tubulin gene were able to resolve
      specimens of each species. Analyses revealed a greater divergence of the beta
      tubulin region than the ITS region. Based on molecular phylogeny of the
      combination of the ITS and beta-tubulin regions, A. muscaria could be separated
      into at least three groups (Eurasian, Eurasian subalpine, and North American),
      and A. pantherina could be separated into at least two groups (North American and
      Eurasian). We hypothesize that the speciation of A. muscaria occurred in Eurasia
      with subsequent migration to North America via land bridges. However, it is
      impossible to determine whether A. pantherina moved from Eurasia to North America
      or vice versa. For both A. muscaria and A. pantherina, the intracontinental
      relationships of both Eurasia and North America were closer than the
      relationships between eastern Asia and eastern North America.

PMID- 15449594
TI  - Genetic diversity shown in Trichoderma biocontrol isolates.
AB  - Genetic variability within 69 biocontrol isolates of Trichoderma, obtained from
      different geographical locations and culture collections and selected as
      biocontrol agents, was studied. Sequence data, obtained from the ITS1 region of
      rDNA and a fragment of the translation elongation factor 1 (tef1) gene, were used
      in a phylogenetic analysis. Phylograms showing similar topologies were generated
      using alignments containing the ITS1 region or a portion of the tef1 gene. 21
      distinct ITS1 sequence types and 17 distinct tef1 sequence types were identified
      among the 69 isolates. More than 50% of the potential biocontrol strains were
      grouped within Trichoderma sect. Pachybasium; of these, 81% were grouped within
      the cluster that included the ex-type strains of T. harzianum and T. inhamatum,
      and 16% were grouped with T. virens. Within T. sect. Trichoderma, which included
      36% of the 69 strains, 56% were grouped with T. asperellum, and 24% with T.
      viride, T. atroviride or T. koningii. Only 10% of the strains studied were
      located in T. sect. Longibrachiatum.

PMID- 15449595
TI  - Mycoviruses in Monilinia fructicola.
AB  - DsRNAs were detected in 36 of 49 Monilinia fructicola isolates from stone fruit
      orchards in New Zealand. The dsRNA profiles were highly variable, even between
      isolates from a single tree. Comparison of pathogenicity on detached fruit, in
      vitro growth rate, and sporulation of 14 isolates showed no obvious correlation
      with presence of dsRNAs. Partially purified extracts from four isolates were
      examined for the presence of virus-like particles by transmission electron
      microscopy. One isolate contained 45 nm isometric particles similar in appearance
      to totiviruses and partitiviruses. A second isolate contained 200-250 x 25 nm
      rigid rods similar in appearance to the plant pathogenic tobraviruses and
      furoviruses. This is the first report of the presence of viral-like agents in the
      brown rot fungus Monilinia fructicola.

PMID- 15449596
TI  - Degradation of juglone by Pleurotus sajor-caju.
AB  - The toxic naphthoquinone juglone (5-hydroxy-1,4-naphthoquinone) is efficiently
      degraded by the ligninolytic fungus Pleurotus sajor-caju, as demonstrated by the
      total bleaching within 9 d of a conventional liquid culture medium supplemented
      with 0.6 mM juglone. The oxidative degradation involves the production of
      hydrogen peroxide arising from both enzymic and non-enzymic oxidation reactions,
      promoted by the fungus. Juglone is not directly attacked by the oxidative enzymes
      of the ligninolytic machinery of P. sajor-caju, such as laccase, manganese
      peroxidase and arylalcohol oxidase. On the other hand, this naphthoquinone is a
      good substrate for a reductase, which triggers an auto-oxidative process
      producing reactive oxygen species and leading to juglone degradation. The
      degradation process continues to completion by means of a direct, presumably non
      catalysed reaction with hydrogen peroxide.

PMID- 15449597
TI  - Efficient degradation of tannic acid by black Aspergillus species.
AB  - A set of aspergillus strains from culture collections and wild-type black
      aspergilli isolated on non-selective media were used to validate the use of media
      with 20% tannic acid for exclusive and complete selection of the black
      aspergilli. The 20% tannic acid medium proved useful for both quantitative and
      qualitative selection of all different black aspergilli, including all recognized
      species: A. carbonarius, A. japonicus, A. aculeatus, A foetidus, A.
      heteromorphus, A. niger, A. tubingensis and A. brasiliensis haplotypes. Even
      higher concentrations of tannic acid can be utilized by the black aspergilli
      suggesting a very efficient tannic acid-degrading system. Colour mutants show
      that the characteristic ability to grow on high tannic acid concentrations is not
      causally linked to the other typical feature of these aspergilli, i.e. the
      formation of brown-black pigments. Sequence analysis of the A. niger genome using
      the A. oryzae tannase gene yielded eleven tannase-like genes, far more than in
      related species. Therefore, a unique ecological niche in the degradation of
      tannic acid and connected nitrogen release seems to be reserved for these black
      spored cosmopolitans.

PMID- 15449598
TI  - Effects of culture media and environmental factors on mycelial growth and
      pycnidial production of Potebniamyces pyri.
AB  - Potebniamyces pyri (anamorph Phacidiopycnis piri) is the causal agent of
      Phacidiopycnis rot of apples and pears. The disease has recently been recognized
      in pears in the USA. Little information on the basic biology of the fungus is
      available. In this paper, we report the effects of culture media, temperature,
      water potential and pH on mycelial growth, and the effects of media and light on
      pycnidia production. Prune juice agar was the best for rapid mycelial growth.
      Pear juice agar, apple juice agar, potato dextrose agar, and oatmeal agar (OMA)
      also favoured mycelial growth. Czapek-Dox agar was not suitable for mycelial
      growth. The fungus was able to grow at temperatures from -3 to 25 degrees C.
      Optimal mycelial growth occurred between 15 and 20 degrees. The average radial
      growth rate on OMA was 3.9 mm d(-1) at 15 degrees and 4.4 mm d(-1) at 20 degrees.
      Mycelial growth was not observed after 10 d at 30 degrees, but growth resumed at
      20 degrees. The fungus failed to resume growth at 20 degrees after being
      incubated for 10 d at 35 degrees. The fungus was able to grow at water potentials
      as low as -4 MPa but no growth took place at -7.3 MPa. Active mycelial growth was
      observed on OMA at pH between 3.2 and 6.1. Optimal growth was observed at pH
      around 4 and no growth was observed at pH 7.1. No pycnidia or very few formed on
      the nine media at 20 degrees in the dark. Fluorescent light significantly
      stimulated formation of pycnidia. OMA was the best medium for production of
      pycnidia and macroconidia. Pycnidia that formed on 8-wk-old OMA cultures
      incubated at 20 degrees under 12 h dark/12 h light produced abundant macroconidia
      and the technique is recommended for inoculum production of conidia for research.

PMID- 15449599
TI  - Some aspects of interrelations between fungi and other biota in forest soil.
AB  - Interrelations of fungal mycelium with other soil biota are of paramount
      importance in forestry and soil ecology. Here we present the results of
      statistical analysis of a comprehensive data set collected in the first (and the
      only) British fungus sanctuary over a period of four months. The variables
      studied included a number of soil properties, bacteria, protozoan flagellates,
      ciliates and amoebae, microbial and plant feeding nematodes, various
      microarthropods, and two fungal biomarkers--glomalin and ergosterol. One way
      ANOVA showed that the dynamics of the microbiota studied was influenced by
      seasonal changes. Superimposed on these changes, however, was variability due to
      biological interactions and habitat characteristics. Two fungal biomarkers,
      ergosterol and glomalin, were differently influenced by other biota and abiotic
      variables. The results indicate that the dynamics of soil fungi is influenced not
      only by soil microarthropods, but also by those found in forest litter. The
      overall outcome, therefore, is likely to be very complex and will depend upon
      specific conditions of any particular ecosystem.

PMID- 15449600
TI  - Nutritional influences on the solubilization of metal phosphate by ericoid
      mycorrhizal fungi.
AB  - Four ericoid mycobionts (two isolates of Hymenoscyphus ericae, and two dark,
      sterile ericoid mycobionts isolated from metal-contaminated mine sites) were
      grown on solid agar plates supplemented with zinc phosphate (0.25 %) containing
      different forms of nitrogen (nitrate, ammonium or alanine) and different
      concentrations of carbon (glucose) and phosphorus (K2HPO4). The influence of
      nutrient variation on solubilizing ability of the fungi was assessed by measuring
      the zones of solubilization appearing beneath the growing colonies. All four
      mycobionts were capable of zinc phosphate solubilization in the presence of all
      three nitrogen sources and in media containing no nitrogen. No solubilization was
      observed at 0 mM glucose-C but was observed with increasing glucose concentration
      from 300 to 600 mM C. Increasing phosphorus concentration (0-5 mM P) had no
      effect on the solubilizing ability of the isolates. All but one of the mycobionts
      were capable of solubilizing calcium phosphate (CaHPO4), while no solubilization
      was observed in media containing aluminium phosphate (AlPO4), iron phosphate
      (FePO4 x 4H2O) or copper phosphate (Cu3O8P2 x 2H2O) under conditions which were
      found to be optimal for zinc phosphate solubilization. Under conditions of
      glucose at 300 mM C and alanine as the N source in the zinc phosphate-amended
      agar medium, one of the mycobionts produced new crystals, which were
      morphologically distinct from the original zinc phosphate crystals. It is
      concluded that medium composition influences the metal-phosphate solubilizing
      ability of ericoid mycobionts. The results are discussed in relation to the
      possible mechanisms involved in solubilization and the potential benefits of
      metal-phosphate solubilization to ericoid mycobionts and their host plants.

PMID- 15449601
TI  - Patterns of genetic variation in Phialocephala fortinii across a broad
      latitudinal transect in Canada.
AB  - Dark septate root endophytes (DSE) are an artificial assemblage of fungi that
      have darkly pigmented, septate hyphae and that are frequent or distinctive
      intracellular associates of roots of apparently healthy plants. Based on isolates
      obtained from the roots of Salix spp., the distribution of a common DSE fungus,
      Phialocephala fortinii, was examined along a latitudinal transect in Canada
      running from the high arctic to the 49 degrees N parallel. Non-sporulating
      isolates were provisionally identified as P. fortinii through analysis of DNA
      sequence data of the ITS2 region of rDNA. P. fortinii was isolated frequently
      from boreal and arctic habitats, but rarely from grassland habitats. Patterns of
      genetic variation were examined through analysis of amplified fragment length
      polymorphisms (AFLP). All AFLP profiles were unique with the majority of genetic
      variation occurring among individuals within the collecting sites at each
      latitude. Neighbour-joining analysis of genetic distances yielded eight well
      supported clusters, three of which included individuals from more than one
      latitude. Some linkage disequilibrium, possibly due to partial clonality, was
      detected.

PMID- 15449602
TI  - Ecology and molecular characterization of dark septate fungi from roots, living
      stems, coarse and fine woody debris.
AB  - The aim of the present work was to determine the identity and molecular
      relationships between 127 strains of dark septate (DS) fungi isolated from
      healthy root tips, decayed coarse roots, live healthy-looking stems, coarse
      (stumps, snags and logs) and fine (tree branches and tops) woody debris in
      temperate-boreal forests in Sweden and Lithuania. Sequence analysis of ITS rDNA
      was used to identify the fungi. In a neighbour-joining similarity tree, all
      sequences were grouped into five distinct clusters. Within each of these, ITS
      rDNA sequence variation consisted of 2-18 nucleotides, corresponding to 1-3% of
      their total length. The four least variable clusters were supported with high
      bootstrap values of 86-100%. Comparisons with the sequences in the GenBank
      database showed that all our strains had a 95-100% homology with identified
      Phialocephala species, and they were thus assigned to this genus. The
      representatives of two clusters were identified, as P. fortinii and P.
      dimorphospora. The representatives of three remaining clusters were defined as
      Phialocephala sp. 35, Phialocephala sp. 6 and Phialocephala sp. 18. Within each
      of these clusters, ITS rDNA sequence uniformity was higher than that observed
      within P. fortinii and P. dimorphospora. Consequently, their clusters were most
      discrete, supported with bootstrap values of 100%. Genetic variation in the five
      distinguished Phialocephala species and their possible ecological roles are
      discussed. Phialocephala sp. 6 was confined to healthy root tips of conifers. P.
      dimorphospora was only associated with dead woody tissue of P. abies. P.
      fortinii, Phialocephala sp. 18 and sp. 35 were isolated from both dead and living
      conifers and Betula pendula. In conclusion, the present study revealed the
      ability of fungi from the genus Phialocephala to colonise and persist in live and
      dead trees under strikingly different ecological conditions.

PMID- 15449603
TI  - Characterization of the melanin pigment of a cosmopolitan fungal endophyte.
AB  - Phyllosticta capitalensis (teleomorph Guignardia mangiferae) occurs as a foliar
      endophyte in woody trees belonging to different families of both temperate and
      tropical regions. We isolated this endophyte from plants in different habitats,
      such as mangroves, dry deciduous forest, moist deciduous forest and semi
      evergreen forest. This endophyte was found to produce a black pigment that was
      characterized to be melanin based on uv-visible, IR and ESR spectra and chemical
      tests. Tricyclazole, a specific inhibitor of pentaketide melanin biosynthesis,
      inhibited synthesis of the pigment indicating it is a 1-8, dihydroxynaphthalene.
      This appears to be the first report of such a melanin in Phyllosticta or other
      foliar endophytes. Melanin in the hyphae of P. capitalensis may be responsible
      for the success of this fungus as a cosmopolitan endophyte, since melanin is
      known to enhance the survival capability of fungi in stressful environments.

PMID- 15449604
TI  - Quorum sensing and swarming migration in bacteria.
AB  - Bacterial cells can produce and sense signal molecules, allowing the whole
      population to initiate a concerted action once a critical concentration
      (corresponding to a particular population density) of the signal has been
      reached, a phenomenon known as quorum sensing. One of the possible quorum sensing
      regulated phenotypes is swarming, a flagella-driven movement of differentiated
      swarmer cells (hyperflagellated, elongated, multinucleated) by which bacteria can
      spread as a biofilm over a surface. The glycolipid or lipopeptide biosurfactants
      thereby produced function as wetting agent by reducing the surface tension.
      Quorum sensing systems are almost always integrated into other regulatory
      circuits. This effectively expands the range of environmental signals that
      influence target gene expression beyond population density. In this review, we
      first discuss the regulation of AHL-mediated surface migration and the
      involvement of other low-molecular-mass signal molecules (such as the furanosyl
      borate diester AI-2) in biosurfactant production of different bacteria. In
      addition, population density-dependent regulation of swarmer cell differentiation
      is reviewed. Also, several examples of interspecies signalling are reported.
      Different signal molecules either produced by bacteria (such as other AHLs and
      diketopiperazines) or excreted by plants (such as furanones, plant signal mimics)
      might influence the quorum sensing-regulated swarming behaviour in bacteria
      different from the producer. On the other hand, specific bacteria can reduce the
      local available concentration of signal molecules produced by others. In the last
      part, the role and regulation of a surface-associated movement in biofilm
      formation is discussed. Here we also describe how quorum sensing may disperse
      existing biofilms and control the interaction between bacteria and higher
      organisms (such as the Rhizobium-bean symbiosis).

PMID- 15449606
TI  - Global carbon/nitrogen control by PII signal transduction in cyanobacteria: from
      signals to targets.
AB  - PII signal transduction plays a pervasive role in microbial nitrogen control.
      Different phylogenetic lineages have developed various signal transduction
      schemes around the highly conserved core of the signalling system, which consists
      of the PII proteins. Among all various bacterial PII signalling systems, the one
      in cyanobacteria is so far unique: in unicellular strains, the mode of covalent
      modification is by serine phosphorylation and the interpretation of the cellular
      nitrogen status occurs by measuring the 2-oxoglutarate levels. Recent advances
      have been the identification of the phospho-PII phosphatase, the resolution of
      the crystal structure of PII proteins from Synechococcus and Synechocystis
      strains and the identification of novel functions of PII regulation in
      cyanobacteria, which highlight the central role of PII signalling for the
      acclimation to changing carbon-nitrogen regimes.

PMID- 15449607
TI  - A challenge for 21st century molecular biology and biochemistry: what are the
      causes of obligate autotrophy and methanotrophy?
AB  - We assess the use to which bioinformatics in the form of bacterial genome
      sequences, functional gene probes and the protein sequence databases can be
      applied to hypotheses about obligate autotrophy in eubacteria. Obligate
      methanotrophy and obligate autotrophy among the chemo- and photo-lithotrophic
      bacteria lack satisfactory explanation a century or more after their discovery.
      Various causes of these phenomena have been suggested, which we review in the
      light of the information currently available. Among these suggestions is the
      absence in vivo of a functional alpha-ketoglutarate dehydrogenase. The advent of
      complete and partial genome sequences of diverse autotrophs, methylotrophs and
      methanotrophs makes it possible to probe the reasons for the absence of activity
      of this enzyme. We review the role and evolutionary origins of the Krebs cycle in
      relation to autotrophic metabolism and describe the use of in silico methods to
      probe the partial and complete genome sequences of a variety of obligate genera
      for genes encoding the subunits of the alpha-ketoglutarate dehydrogenase complex.
      Nitrosomonas europaea and Methylococcus capsulatus, which lack the functional
      enzyme, were found to contain the coding sequences for the E1 and E2 subunits of
      alpha-ketoglutarate dehydrogenase. Comparing the predicted physicochemical
      properties of the polypeptides coded by the genes confirmed the putative gene
      products were similar to the active alpha-ketoglutarate dehydrogenase subunits of
      heterotrophs. These obligate species are thus genomically competent with respect
      to this enzyme but are apparently incapable of producing a functional enzyme.
      Probing of the full and incomplete genomes of some cyanobacterial and
      methanogenic genera and Aquifex confirms or suggests the absence of the genes for
      at least one of the three components of the alpha-ketoglutarate dehydrogenase
      complex in these obligate organisms. It is recognized that absence of a single
      functional enzyme may not explain obligate autotrophy in all cases and may indeed
      be only be one of a number of controls that impose obligate metabolism.
      Availability of more genome sequences from obligate genera will enable assessment
      of whether obligate autotrophy is due to the absence of genes for a few or many
      steps in organic compound metabolism. This problem needs the technologies and
      mindsets of the present generation of molecular microbiologists to resolve it.

PMID- 15449608
TI  - Regulators of nonsulfur purple phototrophic bacteria and the interactive control
      of CO2 assimilation, nitrogen fixation, hydrogen metabolism and energy
      generation.
AB  - For the metabolically diverse nonsulfur purple phototrophic bacteria, maintaining
      redox homeostasis requires balancing the activities of energy supplying and
      energy-utilizing pathways, often in the face of drastic changes in environmental
      conditions. These organisms, members of the class Alphaproteobacteria, primarily
      use CO2 as an electron sink to achieve redox homeostasis. After noting the
      consequences of inactivating the capacity for CO2 reduction through the Calvin
      Benson-Bassham (CBB) pathway, it was shown that the molecular control of many
      additional important biological processes catalyzed by nonsulfur purple bacteria
      is linked to expression of the CBB genes. Several regulator proteins are
      involved, with the two component Reg/Prr regulatory system playing a major role
      in maintaining redox poise in these organisms. Reg/Prr was shown to be a global
      regulator involved in the coordinate control of a number of metabolic processes
      including CO2 assimilation, nitrogen fixation, hydrogen metabolism and energy
      generation pathways. Accumulating evidence suggests that the Reg/Prr system
      senses the oxidation/reduction state of the cell by monitoring a signal
      associated with electron transport. The response regulator RegA/PrrA activates or
      represses gene expression through direct interaction with target gene promoters
      where it often works in concert with other regulators that can be either global
      or specific. For the key CO2 reduction pathway, which clearly triggers whether
      other redox balancing mechanisms are employed, the ability to activate or
      inactivate the specific regulator CbbR is of paramount importance. From these
      studies, it is apparent that a detailed understanding of how diverse regulatory
      elements integrate and control metabolism will eventually be achieved.

PMID- 15449605
TI  - Outer membrane proteins of pathogenic spirochetes.
AB  - Pathogenic spirochetes are the causative agents of several important diseases
      including syphilis, Lyme disease, leptospirosis, swine dysentery, periodontal
      disease and some forms of relapsing fever. Spirochetal bacteria possess two
      membranes and the proteins present in the outer membrane are at the site of
      interaction with host tissue and the immune system. This review describes the
      current knowledge in the field of spirochetal outer membrane protein (OMP)
      biology. What is known concerning biogenesis and structure of OMPs, with
      particular regard to the atypical signal peptide cleavage sites observed amongst
      the spirochetes, is discussed. We examine the functions that have been determined
      for several spirochetal OMPs including those that have been demonstrated to
      function as adhesins, porins or to have roles in complement resistance. A
      detailed description of the role of spirochetal OMPs in immunity, including those
      that stimulate protective immunity or that are involved in antigenic variation,
      is given. A final section is included which covers experimental considerations in
      spirochetal outer membrane biology. This section covers contentious issues
      concerning cellular localization of putative OMPs, including determination of
      surface exposure. A more detailed knowledge of spirochetal OMP biology will
      hopefully lead to the design of new vaccines and a better understanding of
      spirochetal pathogenesis.

PMID- 15449609
TI  - Can whole genome analysis refine the taxonomy of the genus Rhodococcus?
AB  - The current systematics of the genus Rhodococcus is unclear, partly because many
      members were originally included before the application of a polyphasic taxonomic
      approach, central to which is the acquisition of 16S rRNA sequence data. This has
      resulted in the reclassification and description of many new species. Hence, the
      literature is replete with new species names that have not been brought together
      in an organized and easily interpreted form. This taxonomic confusion has been
      compounded by assigning many xenobiotic degrading isolates with phylogenetic
      positions but without formal taxonomic descriptions. In order to provide a
      framework for a taxonomic approach based on multiple genetic loci, a survey was
      undertaken of the known genome characteristics of members of the genus
      Rhodococcus including: (i) genetics of cell envelope biosynthesis; (ii) virulence
      genes; (iii) gene clusters involved in metabolic degradation and industrially
      relevant pathways; (iv) genetic analysis tools; (v) rapid identification of
      bacteria including rhodococci with specific gene RFLPs; (vi) genomic organization
      of rrn operons. Genes encoding virulence factors have been characterized for
      Rhodococcus equi and Rhodococcus fascians. Based on peptide signature comparisons
      deduced from gene sequences for cytochrome P-450, mono- and dioxygenases, alkane
      degradation, nitrile metabolism, proteasomes and desulfurization, phylogenetic
      relationships can be deduced for Rhodococcus erythropolis, Rhodococcus
      globerulus, Rhodococcus ruber and a number of undesignated Rhodococcus spp. that
      may distinguish the genus Rhodococcus into two further genera. The linear genome
      topologies that exist in some Rhodococcus species may alter a previously proposed
      model for the analysis of genomic fingerprinting techniques used in bacterial
      systematics.

PMID- 15449610
TI  - [Experimental studies and clinical application of quickly prefabricated random
      skin flap].
AB  - OBJECTIVE: To enlarge the ratio of length to width of a prefabricated random skin
      flap in a short period, in order to meet a special clinical need. METHODS: A
      white rat and a white mini-pig was chosen for an animal model for the experiment.
      They were divided into the experimental group and the control. The prefabricated
      flap was formed as the planned design. In the experimental group, the flaps were
      treated with a desired pressure in certain intervals at the planned part of the
      flap. We estimated and inspected the digitized perfusion of flap
      microcirculation, and made overcong and wide random skin flap survive within 24
      hours, and this technique was finally used for the clinical wound treatment.
      RESULTS: As expected, the survival area of the flap in the experimental group was
      significantly larger than the control. This technique was successfully used to
      repair the defects of the special sites in plastic and reconstructive surgery.
      CONCLUSION: The method of quickly prefabricated random flap could enlarge the
      ratio of length to width of the flap and put the flap in shape in short time.
      With the digitized estimating and inspecting, this method could obviously improve
      the survival area of the random flap and could also be very useful for the
      clinical treatment.

PMID- 15449611
TI  - [Clinical application of the fibrous capsule to prevent muscle tendon adhesion].
AB  - OBJECTIVE: To observe the effect of fibrous capsule to prevent the flexor tendon
      adhesion. METHODS: Six bum patients with 33 digits were treated with the fibrous
      capsule of the expanded flaps which was used to wrap the exposed flexor tendon in
      zone III in order to prevent the flexor tendon adhesion. RESULTS: From 1999-2001
      ,all of the patients were followed up to 1-3 years. The functions, assessed with
      the TAM method, were excellent in 18 digits, fair in three and poor in one. The
      excellent and good rate was 87.88%. CONCLUSION: The fibrous capsule could be used
      to prevent or reduce the tendon adhesion.

PMID- 15449612
TI  - [Hemodynamic study of an over-midline axial flap].
AB  - OBJECTIVE: To investigate the hemodynamic changes of an over-midline axial flap.
      METHODS: An over-midline axial flap, based on the iliac artery and veins, was
      raised on the back of each selected Wistar rat (n = 30), vascularied by
      contralateral. The flap size is 7 cm x 3 cm. The over-midline part is 3 cm x 3
      cm. A laser doppler flowmetry (LDF) was used to evaluate the hemodynamic changes
      preoperatively, and 6 hours, 24 hours, 48 hours, 72 hours, 7 days, and 14 days
      after the operation respectively. RESULTS: All of the flaps survived well. But,
      in the first three days after the operation, the blood perfusion of the flap in
      the areas of the midline and the distal part was significantly lower than the
      preoperation's level. Thereafter, the values of the blood perfusion started to
      increase till to the maximum 7 days after the operation. On the 14 days after the
      operation, the vascular structures was axially matched to the base of the flap.
      In the distal part of the flap, the choke vessels were gradually opened and
      resulted in the blood perfusion to the normal level. CONCLUSION: The hemodynamic
      changes of the over-midline axial flap transmidline flap could occur to match the
      need of the base of the flap.

PMID- 15449613
TI  - [The reason and management of the sunken upper eyelid after hydroxyapatite
      platform implantation].
AB  - OBJECTIVE: To study the reason and the management of the sunken upper eyelid
      after implanting a hydroxyapatite platform. METHODS: From 1998, we developed a
      method of subperiosteal implantation at the orbital floor to repair the
      introcession of the upper eyelid after hydroxyapatite platform implantation. 11
      cases of the sunken upper eyelid were treated with this method. The implants
      included Medpor in 2 cases, hydroxyapatite plates in 7 cases and acellular dermal
      matrix in 2 cases. RESULTS: Postoperatively, all the patients obtained
      satisfactory results. Follow-up for 1 to 4 years showed no complications of
      extrusion or infection of the implants. Re-operation was needless in all of them.
      CONCLUSION: Subperiosteal implantation to correct the sunken upper eyelid is a
      safe and effective method.

PMID- 15449614
TI  - [Semiconductor low level laser irradiation for exposure of hydroxyapatite orbital
      implants].
AB  - OBJECTIVE: To evaluate the efficacy of semiconductor low level laser irradiation
      for the treatment of postoperative exposure of hydroxyapatite orbital implants.
      METHODS: 22 cases with postoperative exposure of hydroxyapatite orbital implants
      were divided into three groups according to the size of implants exposure. The
      exposure wound in the 3 groups was irradated with semiconductor low level laser 5
      min per day for 5-15 days. The follow-up period ranged from 2 to 24 months.
      RESULTS: In the group with less then 3 mm of exposure, the wound healed in 1 week
      after 5-10 days irradiation; in the group with implant exposure of 4-7 mm, the
      would healed in 1-2 weeks after 10-15 days irradiation; in the group with implant
      exposure of 8-10 mm, the would healed in 2-3 weeks after 10-15 days irradiation.
      Compared with the treatments of drugs and/or surgical repair, which was used for
      another 20 cases of exposure of hydroxyapatite orbital implants, semiconductor
      low level laser increased healing rate obviously in the groups with implant
      exposure of 4-7 mm and 8-10 mm (P = 0.019, 0.018). CONCLUSION: Semiconductor low
      level laser has better effects than drugs and/or surgical repair for exposure of
      hydroxyapatite orbital implants.

PMID- 15449615
TI  - [Experimental study of the biocompatible and osteoinductive behavior of the
      hydroxyapatite/ultra-high molecular weight polyethtlene composite].
AB  - OBJECTIVE: To compare the biocompatibility and osteoinductive behavior of HA
      (hydroxyapatite) and HA/UHMWPE (ultra-high molecular weight polyethtlene)
      composite in orbital implantation. METHODS: Osteoectomy of the upper orbital rim
      was perform on 24 adult New Zealand rabbits. The animals were randomly divided
      into 4 groups with 6 of each. The HA, HA/UHMWPE composite or UHMWPE (10 mm x 10
      mm x 3 mm in size) was implanted to the upper orbital defect of the animal in
      respective group. Animals were sacrificed at 1, 4, 8, 12 weeks. Histopathologic
      sections of the implants were evaluated and compared with light and transmission
      electron microscopy study. RESULTS: During the experimental period of 12 weeks,
      there was no implant extrusion or displacement. In the groups of HA and HA/UHMWPE
      composite, vascular ingrowth and fibroblasts were observed shortly and osteocytes
      were seen at 8 weeks. Calcium deposition of the implants showed a laminar fashion
      at 12 weeks. In the group of UHMWPE, fibrous membranes were seen around the
      implant at 1 week. Transmission electron microscopy study showed that in the HA
      and HA/UHMWPE groups, fibroblasts and vascular ingrowth could be seen, but
      osteocytes were not observed. CONCLUSION: HA/UHMWPE composite demonstrated
      biocompatibility and osteoinductive property. It would be a good substitute for
      bone, particularly for orbital bone.

PMID- 15449616
TI  - [Management of secondary nasolabial deformities after bilateral cleft lip
      repair].
AB  - OBJECTIVE: To evaluate the method to correct the seconary nasolabial deformities
      after the surgical treatment in the patients with bilateral cleft lip. METHODS:
      From January 2000 to June 2003, forty patients with secondary deformities
      following repair of bilateral cleft lip were treated with a combined treatment
      procedures. AU of the forty cases underwent the following preoperative
      treatments: alveolar bone graft in 28 cases, preoperative orthodontics in 22
      cases, prosthodontics in 20 cases and orthognathic surgery or distraction
      osteogenesis treatment in 20 cases, respectively. In order to improve the
      enlongation of nasal column, reconstruction of Cupid's bow, philtrum and
      correction procedures, continuous incision was made from the vermilion in median
      of the upper lip, the scar edge, the bilateral sides of the nasal column to the
      inner side of the nose, even extending the bilateral incision to nasolabial
      groove and nostril fundus. RESULTS: Forty patients were got the follow-ups for 3
      months to 3.5 years and the satisfactory rate reached 95%. CONCLUSION: It is
      natural to emphasize the setting up of odontomaxillary frame and then utilize the
      surgical procedure to correct the secondary nasolabial parenchyma deformities.
      The method could be feasible and reliable for the correction of the secondary
      nasolabial parenchyma deformities after bilateral cleft lip repair.

PMID- 15449617
TI  - [The usage of inferior turbinate mucosal flap for repairing cleft lip].
AB  - OBJECTIVE: To evaluate a technique for decreasing the tension of the nasal floor
      during the procedures of repairing complete clef lip. METHODS: With the
      designation of an inferior turbinate mucosal flap combined with an oral mucosal
      flap in the splitting side, the tension was effectively decreased and the nasal
      floor was closed easily. Eighteen patients was selected for the treatment with
      this technique since 2000. The follow-ups were 10 to 24 months. RESULTS: All of
      the patients showed wound healing well with the significant improvement in the
      donor site. CONCLUSION: The above mentioned technique may effectively decrease
      the tension and be used to close the nasal floor safely. It could also reduce the
      incidence of the complications.

PMID- 15449618
TI  - [The TGF-alpha gene Taq I polymorphism and non-syndromic cleft lip with or
      without cleft palate].
AB  - OBJECTIVE: To study the association of TGF-alpha gene Taq I polymorphism and
      nonsyndromic cleft lip with or without cleft palate (NSCL/P) in Chinese. METHODS:
      107 patients with NSCL/P and 136 healthy controls were examined for TGF-alpha/Taq
      I genotypes. TGF-alpha/Taq I typing was carried out by digesting the locus
      specific polymerase chain reaction amplified products with alleles specific Taq I
      restriction enzyme (PCR-RELP). RESULTS: The C2 allele frequency of TGF-alpha/Taq
      I in patients with NSCL/P (16%) was significantly higher than that in healthy
      controls (8%). The C2 genotype frequency of TGF-alpha/Taq I in NSCL/P patients
      with positive family history (12.5%) was significantly higher than that in
      healthy controls. CONCLUSION: These findings demonstrate the role of TGF-alpha as
      a gene of major effects in the development of nonsyndromic cleft lip with or
      without cleft palate clefts in human. These findings suggest that a family
      history of clefting may correlate with the TGF-alpha Taq I rare variation.

PMID- 15449619
TI  - [The investigation of behavior problem with secondary deformity of cleft lip].
AB  - OBJECTIVE: To investigate the behaviors of the children suffered from the
      secondary deformity after the repair of the cleft lip. METHODS: With the
      application of the PCPI, eighty patients with the secondary deformity after the
      repair of the cleft lip were selected in this study and 134 normal children was
      used for the control. RESULTS: In the age between 6 and 11 years, there were no
      significant difference of the behaviors between the children suffered from
      secondary deformity of cleft lip and the normal children,but in the age from 12
      to 16, the children with the deformity showed more behavior problems with the
      social withdraw and the poor social relationships, compared with the normal
      children. CONCLUSION: The children with the secondary deformity after cleft lip
      repair in adolescence could have the tendency to suffer from the behavior
      problems, especially showing the social withdraw and the poor social
      relationships.

PMID- 15449620
TI  - [Applications of magnetic resonance imaging in diagnosis of the complications
      after breast augmentation with polyacrylamide hydrogel injection].
AB  - OBJECTIVE: To explore the clinical value of magnetic resonance (MR) imaging in
      the diagnosis of the complications after breast augmentation with polyacrylamide
      hydrogel injection. METHODS: MRI was performed in 16 patients who had breast
      augmentation with polyacrylamide hydrogel injection. The results of magnetic
      resonance imaging were compared with the clinical symptoms. RESULTS: MRI
      examinations of the 16 patients showed that (1) 4 breasts in 2 patients were
      comparatively natural; (2) a large lacteal cyst was detected in one patients in
      lactation; (3) breast asymmetry occurred in 3 patients (6 sides); (4) in 10
      patients (20 sides), the injected gel was in irregular form. The results of MRI
      were in accord with the clinical symptoms. CONCLUSION: MRI is of great diagnostic
      value for the complications after breast augmentation with polyacrylamide
      hydrogel injection.

PMID- 15449621
TI  - [Treatment of the complications of polyacrylamide hydrogel injection for
      augmentation mammaplasty].
AB  - OBJECTIVE: The purpose of this study was to search for a perfect treatment for
      the complications after polyacrylamide hydrogel injection for augmentation
      mammaplasty. METHODS: 48 patients who accepted polyacrylamide hydrogel injection
      for augmentation mammaplasty were included in this study. Operations were
      performed for the complications of polyacrylamide hydrogel injection. The
      clinical data were analyzed and the experience in the treatment of the
      complications was summarized. RESULTS: All patients were satisfied with the
      result of the operation. The B-ultrasonic examination showed that no visible
      polyacrylamide hydrogel remained in the cavity. CONCLUSION: The best therapy for
      the complications of polyacrylamide hydrogel injection was removing of the
      polyacrylamide hydrogel and the pathologic tissue and irrigation of the cavity.

PMID- 15449622
TI  - [An experiment study and clinical observation of the testicle spermatogenesis
      after scrotum reconstruction].
AB  - OBJECTIVE: To explore the effect of scrotum reconstruction with a skin flap on
      spermatogenesis. METHODS: Two patients who underwent scrotum reconstruction with
      the skin flap were followed up for four years. Their sperm quality, sex function,
      sexual hormone, and testis biopsy were examined. To exclude the influential
      factors of testis and spermatic cord contusing, an experiment study was designed
      and performed in rabbits. The scrotal skin of the rabbits was stripped off and
      the scrotum was reconstructed with a hypogastric skin flap. RESULTS: The clinical
      follow-up indicated that in the early postoperative period, the reconstruction
      did not impede spermatogenesis, but the arrest of spermatogenesis happened with
      time. The experimental results showed that the sperm count of the rabbits
      decreased obviously and the rabbits became sterile two months after scrotum
      reconstruction. CONCLUSION: The thick skin flap is not recommended for scrotum
      reconstruction.

PMID- 15449623
TI  - [Fronto-temporal anatomy and its application for augmentation plasty].
AB  - OBJECTIVE: To decide the safe dissection plane and evaluate the multiple
      materials used for the fronto-temporal augmentation. METHODS: Clinical anatomical
      observation were made during the fronto-temporal operations. Forty-one patients
      were treated for the fronto-temporal augmentation with various granular or
      patched materials in different anatomical plane. RESULTS: Four relatively safe
      dissection planes were found in the fronto-temporal area: (1) subcutaneous or
      above superficial temporal fascia, (2) subgalea plane 1.5 cm above the zygomatic
      arch, (3) between the deep temporal fascia and the temporal muscle, and (4)
      beneath the temporal periosteum. With the follow-ups from 6 months to 1 year, the
      appearance after the fronto-temporal augmentation in each patient was
      satisfactory or improved, except for the fat granule group with partial
      absorption and the ePTFE or Medpor hypothesis group shown a stepped contouring at
      the margin in a few patients. CONCLUSION: Four dissection planes could be shown
      in the fronto-temporal region for the augmentation plasty with different
      advantages and disadvantages. The combination could be overcome the disadvantages
      to improve the results. Fat granule could be the best autograft for
      frontotemporal augmentation.

PMID- 15449624
TI  - [Applications of autogenous outer table of the calvarial and mandibular bone in
      posttraumatic deformities of the nose].
AB  - OBJECTIVE: To study the applications of bone grafts from the cranium or mandible
      in the repair of posttraumatic deformities of the nose. METHODS: From 1997 to
      2002, a total of 44 patients, who presented with secondary nose deformity as well
      as facial fractures, were reconstructed by autogeneous outer table grafts of the
      calvarial or mandibular bone after facial skeleton reposition. In this series, 32
      cases used the calvarial bone, 12 cases used the mandible bone, which was
      harvested through a coronal incision and an oral approach respectively. RESULTS:
      The surgical incisions healed primarily in all patients with minimal scar. The
      facial appearance was greatly improved. No implant infection, extrusion and shift
      were observed in the postoperative follow-up of 6 months to 2 years. There was
      not obvious bone resorption, nor donor site morbidity. CONCLUSION: Autogeneous
      calvarial and mandibular bone was an ideal material of bone graft in
      reconstruction of severe posttraumatic deformities of the nose. Compared with
      other autogeneous and alloplastic materials, the outer table of the calvarial and
      mandibular bone produced less morbidity of the donor site, invisible scar, no
      rejection and less resorption.

PMID- 15449625
TI  - [The role of tyrosine phosphorylation proteins in procollagen gene expression of
      fibroblasts in wound healing].
AB  - OBJECTIVE: To investigate the role of adhesion between fibronectin and
      fibroblasts in wound healing as well as tyrosine phosphorylation proteins in
      procollagen mRNA expression. METHODS: The level of proalpha1 (I) mRNA and
      tyrosine phosphorylation protein were detected employing the techniques of RT-PCR
      and immunoblotting. After inhibition of tyrosine kinases, herbimycin A was added
      to the medium to block the pathway of tyrosine phosphorylation, the changes of
      procollagen mRNA and tyrosine phosphorylation proteins were further investigated.
      RESULTS: The adhesion between fibroblasts and fibronectin in wound healing not
      only induced the production of 98kd and 65kd tyrosine phosphorylation protein,
      but also enhanced obviously the expression of procollagen alpha1 (I) mRNA. When
      the pathway of tyrosine phosphorylation was blocked, the level of procollagen
      alpha1 (I) mRNA lowered remarkably, accompanied by the decrease of 98kd, 65kd
      tyrosine phosphorylation proteins. CONCLUSION: The adhesion between fibronectin
      and fibroblasts plays an important role in expression increase of procollagen
      mRNA during wound healing, in the process of which tyrosine phosphorylation is a
      key step.

PMID- 15449626
TI  - [Regeneration of autologous tissue-engineered cartilage by using basic-fibroblast
      growth factor in vitro culture].
AB  - OBJECTIVE: To investigate the effect of the basic fibroblast growth factor (b
      FGF) to regenerate an autologous tissue-engineered cartilage in vitro. METHODS:
      The Cells were harvested from the elastic auricular cartilage of swine,and were
      plated at the concentration of 1 x 10(4) cells/cm2 , studied in vitro at two
      different media enviroments: Group I contained Ham's F-12 with supplements and b
      FGF, Group II contained Ham's F-12 only with supplements. The passage 2 cells
      (after 12.75 +/- 1.26 days) were harvested and mixed with 30% pluronic F
      127/Ham's F-12 at the concentration of 50 x 10(6) cells/ml. It was injected
      subcutaneously at 0.5 ml per implant. The implants were harvested 8 weeks after
      the vivo culture and examined with the histological stains. RESULTS: The
      chondrocytes displayed morphologically similar to the fibroblasts in the media
      containing basic-FGF. The number of cell doublings (after 12.75 +/- 1.26 days) in
      vitro culture was as the following: Group I, 70; Group II, 5.4. Eight 8 weeks
      after the vivo autologous implantation, the average weight (g) and volume (cm3)
      in each group was as the following: Group I, 0.371 g/0.370 cm3 Group II, 0.179
      g/0.173 cm3 (P < 0.01). With the b-FGF in vitro culture, the cells were expanded
      by 70 times after 2 weeks. Histologically, all of the engineered cartilage in the
      two groups were similar to the native elastic cartilage. CONCLUSION: These
      results indicate that the basic-FGF could be used positively to enhance the
      quality and quantity of the seeding cells for the generation of the well
      engineered cartilage.

PMID- 15449627
TI  - [Evaluation of a compound with dan-shen root and azone for scar treatment].
AB  - OBJECTIVE: To evaluate the effect of the compound of Dan-shen root and azone for
      scar treatment. METHODS: The rat skin in vitro and the human skin in vitro and
      vivo were separately examined their permeability of the mixture of the Dan-shen
      root and azone. The 301 patients with hypertrophic scar were randomly divided
      into two groups: one treated with elastic cloth paste (including silicone)
      contained in Dan-shen root with azone, and the another treated with only elastic
      cloth paste (including silicone). RESULTS: The permeability of Dan-shen root with
      azone, passing through the rat skin in vitro and the human skin in vitro and vivo
      was significantly higher than both the distilled water and the normal saline (P <
      0.05). In the clinical study for treatment of the hypertrophic scars, the
      efficient rate of the group with the Dan-shen root with azone was significantly
      higher than the control (91.4% vs. 71.3%) (P < 0.01). CONCLUSION: The Dan-shen
      root with azone could be easier to permeate the skin and more effective to treat
      the hypertrophic scar.

PMID- 15449628
TI  - [Gene expression of extracellular-signal regulated protein kinase 5 and their
      MAPKK in fetal skin hypertrophic scars].
AB  - OBJECTIVE: To explore the change of gene expression of extracellular-signal
      regulated protein kinase 5 (ERK5) and its upstream signaling molecule (MEK5) in
      fetal skin of differentially developmental stages and hypertrophic scars.
      METHODS: After morphological characteristics of skin of different developmental
      stages and hypertrophic scars were detected with pathological methods, gene
      expression of ERK5 and MEK5 was examined with reverse transcription-polymerase
      chain reaction analysis (RT-PCR). RESULTS: In early gestational fetal skin, genes
      of ERK5 and MEK5 were strongly expressed, while in late gestational skin and
      children skin, the expression of ERK5 and MEK5 was apparently decreased (P <
      0.05). In normal skin, the level of gene expression of ERK5 was lower. In
      proliferative hypertrophic scars, mRNA content of this gene was apparently
      increased. In mature scars, the content of this gene transcript was 3.2 times the
      normal skin. In contrast, the levels of MEK5 transcript in normal skin and
      hypertrophic scars of various phases showed no substantial changes (P > 0.05).
      CONCLUSION: ERKS medicating signaling pathway might be involved in regulating
      cutaneous development at the embryonic stage and determining cutaneous structure
      ad function. The increase of gene transcription of ERK5 and MEK5 in younger fetal
      skin might be a reason for rapid proliferation of the skin cells and scraless
      healing of skin. The activation of ERK5 gene expression in hypertrophic scars
      versus normal skin might be one of the mechanisms controlling the formation of
      hypertrophic scars, in which the role of MEK5 needed to be further studied.

PMID- 15449629
TI  - [Cloning of human angiogenesis inhibitor METH1 and its expression in mammalian
      cells].
AB  - OBJECTIVE: To get the full length of human METH1 cDNA and express it steadily in
      mammalian cell stably. METHODS: METH1 was amplified by RT-PCR, and cloned into
      pCDNA3.0 after confirmed by sequence analysis. HepG2 cells were transfected by
      Lipofectamine reagent and then selected in medium with G418. The expression level
      of METH1 was detected by RT-PCR and Western blot. RESULTS: METH1 with expected
      length was effectively amplified, and completely matched the published sequence
      of encoding mature peptide [GI:5725505] as shown by sequence analysis. Eukaryotic
      vector expressing METH1 was obtained by gene cloning, cells expressing METH1 was
      got by selection with G418 at 3 weeks after transfection. RT-PCR and Western blot
      showed high level expression of METH1. CONCLUSION: Full length of human METH1
      gene is cloned successfully and expressed in HepG2 steadily, The results set up a
      basis for the study of effects of METH1 on hypertrophic scar angiogenesis.

PMID- 15449630
TI  - [The correlation between the expansion volume and the contents of b-FGF and EGF
      in the expanded skin].
AB  - OBJECTIVE: To study the correlation between the expansion with different volume
      and the contents of the b-FGF and EGF in the expanded skin. METHODS: The piglets
      were used in the experiment,which were divided into 7 groups including the sham,
      the blank control,the experimental groups with inflation of 1/2 volume, 3/4
      volume, full volume, 150% volume and 200% volume. When expansion was complete, b
      FGF was measured using enzyme coagulate method. EGF was measured by
      radioimmunoassay. The data were analyzed statistically. RESULTS: The contents of
      b-FGF and EGF in the expanded skin was significantly higher than normal skin (P <
      0.05). The difference in contents of b-FGF and EGF between the over-expanded skin
      and normal skin was more significant (P < 0.01). CONCLUSION: Expansion can lead
      to the increase of b-FGF and EGF contents in the expanded skin.The biological
      effects may be relative to epidermal hyperplasia and angiogenesis of the expanded
      skin.

PMID- 15449631
TI  - Discounting health outcomes in economic evaluation: the ongoing debate.

PMID- 15449632
TI  - The economic impact of payer policies after the Rx-to-OTC switch of second
      generation antihistamines.
AB  - OBJECTIVE: As a result of the over-the-counter (OTC) introduction of loratadine,
      health plans have been struggling to determine the best policy to incorporate
      this change within their existing drug benefit structure for second-generation
      antihistamines (SGA). The objective of this study was to examine the economic
      impact of payer policies in response to the Rx-to-OTC switch of loratadine. STUDY
      DESIGN: Decision analysis was used to model the budgetary impact and cost
      effectiveness of four policies for SGA benefits for the managed care organization
      (MCO), employer, and Medicaid perspectives separately. PATIENTS AND METHODS:
      Outcomes included direct medical costs and lost productivity (employers only),
      discounted, quality-adjusted life-years (QALYs) saved because of amelioration of
      allergic rhinitis symptoms and avoidance of unintentional injuries associated
      with the use of first-generation antihistamines (FGA). Bayesian probabilistic
      sensitivity analysis was conducted using second-order Monte Carlo simulation.
      RESULTS: Providing limited OTC and second-tier prescription benefits would cost
      approximately 0.13 dollars and 0.30 dollars compared to third-tier prescription
      benefits for employers and MCOs, respectively, and would save Medicaid 0.02
      dollars per member per month (PMPM). Providing limited coverage for OTC
      loratadine while retaining second-tier prescription benefits for SGA was the
      optimal policy for a willingness to pay below 26,200 dollars per QALY for all
      payers. CONCLUSIONS: Offering second-tier prescription and limited OTC benefits
      provides greater effectiveness and is not significantly more expensive PMPM than
      discontinuation. Some of the drug savings from limiting coverage of prescription
      SGA may be attenuated by the cost of lost productivity and direct medical
      expenditures due to unintentional injuries associated with increased FGA use in
      addition to the increased cost of therapeutic substitutes.

PMID- 15449633
TI  - Cost-effectiveness of low-level heat wrap therapy for low back pain.
AB  - OBJECTIVES: To evaluate the cost-effectiveness and budget impact of a new heat
      wrap therapy for low back pain compared to paracetamol and ibuprofen from the
      perspective of the UK National Health Service (NHS). METHODS: We evaluated cost
      effectiveness using data from a phase III trial comparing the three therapies in
      371 patients aged 18 to 55 years presenting with acute uncomplicated low back
      pain. The primary effectiveness measure used was successful treatment, defined as
      both clinically meaningful pain relief and clinically meaningful reduction in
      disability. We conducted a simple evaluation using NHS prescription costs and a
      modeled extrapolation including the costs of further treatment and consultations
      for patients treated unsuccessfully or with adverse events. Uncertainty was
      addressed using nonparametric bootstrapping and sensitivity analyses. RESULTS:
      Successful treatment was reported by 57% of patients treated with heat wrap
      therapy, 26% treated with paracetamol and 18% treated with ibuprofen (P < 0.05
      for heat wrap vs. both other groups). NHS prescription cost per patient was
      estimated to be 1.35 pounds Sterling for heat wrap therapy, 0.26 pounds Sterling
      for paracetamol, and 0.28 pounds Sterling for ibuprofen and cost per successful
      treatment was 3.52 pounds Sterling for heat wrap therapy compared to paracetamol,
      and 2.72 pounds Sterling compared to ibuprofen. In the modeled extrapolation, NHS
      cost per patient was 27.77 pounds Sterling for heat wrap therapy, 34.20 pounds
      Sterling for paracetamol, and 36.04 pounds Sterling for ibuprofen. Sensitivity
      analyses indicated that the findings were robust to plausible changes in data and
      assumptions. CONCLUSIONS: Economic evaluation of this study suggests that the NHS
      cost of introducing heat wrap therapy in place of oral analgesics would be modest
      and heat wrap therapy might potentially reduce the total cost of managing
      episodes of lower back pain.

PMID- 15449634
TI  - Cost-utility of adjuvant high-dose interferon alpha therapy in stage III
      cutaneous melanoma in Quebec.
AB  - OBJECTIVE: To estimate the cost-utility of adjuvant high-dose interferon in high
      risk melanoma patients in Quebec compared to a watchful waiting strategy. METHOD:
      A Markov model was developed that replicates the findings of the pivotal E1684
      trial. It was then used to extrapolate survival over a period of 35 years. Costs
      of medical resources used during the first year were derived through a detailed
      analysis of a sample (n = 13) of patients treated in a leading academic hospital.
      Follow-up costs were assessed through a medical decision algorithm. Utilities
      were derived from a population-based survey (n = 104) in different locations in
      Quebec using the time trade-off method. RESULTS: The mean incremental cost per
      quality-adjusted life-year of adjuvant Interferon therapy is equal to 55,090 CAN
      dollars over a follow-up of 7 years but drops down to 14,003 CAN dollars when
      extrapolated over 35 years. CONCLUSIONS: Estimates of the cost-effectiveness of
      high-dose interferon in melanoma patients show an acceptable cost-effectiveness
      ratio if long-term survival is taken into account. Estimates are, however,
      strongly influenced by the observed trial differences in survival, the utility
      associated to health states, and the discount rate.

PMID- 15449635
TI  - Costs and benefits of influenza vaccination and work productivity in a Colombian
      company from the employer's perspective.
AB  - OBJECTIVES: This study was designed to evaluate the effects of an employee
      influenza vaccination campaign, measured in terms of health and economic
      benefits. METHODS: Colombian bank employees volunteered to take part in this
      prospective observational study involving two groups: vaccinated and
      nonvaccinated. Socioeconomic and health status information, including influenza
      like symptoms, sick leave, and postvaccination adverse events, were collected via
      questionnaires. Cost-benefit analyses were performed to determine whether the
      employer would save money overall by paying for the vaccination program. RESULTS:
      Between October 2000 and May 2001, 424 vaccinated subjects and 335 nonvaccinated
      subjects volunteered to join the study. Cumulative incidence of influenza-like
      illness (ILI) was lower among vaccinated (14.6%) than nonvaccinated subjects
      (39.4%). Fever was the most common ILI symptom (93% of all reported ILI). Absence
      rates because of ILI were similar in the two groups (2.59%-2.69%). Assuming that
      employees with ILI who continue to work have reduced effectiveness (30%-70% of
      normal) the employer can save 6.4 US dollars to 25.8 US dollars per vaccinated
      employee based on labor costs alone. This saving increases to 89.3 US dollars to
      237.8 US dollars when operating income is also considered. Sensitivity analyses
      indicate that the vaccination program will be cost saving for vaccination
      coverage above 20% and ILI rates above 10%. CONCLUSIONS: Among the studied
      volunteers, ILI has significant impact on work productivity in terms of indirect
      costs. Implementing an influenza vaccination program would reduce the burden of
      ILI and save substantial amounts of money for the company.

PMID- 15449636
TI  - Patient preference and willingness-to-pay for Humalog Mix25 relative to Humulin
      30/70: a multicountry application of a discrete choice experiment.
AB  - OBJECTIVES: To assess preference and willingness-to-pay (WTP) for the insulin
      mixture Humalog Mix25 relative to Humulin 30/70, from the patients' perspective,
      the relative importance of individual treatment attributes was also determined.
      Differences among five European countries were investigated. METHODS: Two hundred
      and ninety patients with type 2 diabetes were recruited from five European
      countries. Of these, 235 were suitable for inclusion in the analysis. Their mean
      age was 51.3 years and, on average, patients had had diabetes for 11 years. A
      discrete-choice conjoint analysis was conducted using face-to-face interviews.
      Treatment attributes, such as timing of injections around meals, 2-hour
      postprandial control, effect of prandial dosing, frequency of nocturnal
      hypoglycemia, and cost, and levels were derived after a systematic review of all
      published comparative clinical trial data. Meta-analyses were undertaken where
      appropriate. RESULTS: Ninety percent (95% CI 86-93%) of patients would choose
      Humalog Mix25 over Humulin 30/70, at the same cost. On average, European subjects
      were willing to pay 111 euros per month more for Humalog Mix25 (95% CI 86.71
      156.91 euros). The primary driver was the reduced risk of nocturnal hypoglycemic
      events, contributing 49% of WTP. The convenience of dosing immediately before the
      meal contributed 37%. Preference results were similar in all five countries,
      although WTP and sensitivity to increasing cost both varied. CONCLUSIONS:
      Patients in all countries showed a preference and WTP for Humalog Mix25 over
      Humulin 30/70. The main drivers of patient WTP may be of interest to
      pharmaceutical prescribers, manufacturers, and reimbursement agencies.

PMID- 15449637
TI  - The impact of urinary urgency and frequency on health-related quality of life in
      overactive bladder: results from a national community survey.
AB  - OBJECTIVES: Overactive bladder (OAB) is described as urinary urgency, with and
      without urge incontinence and usually with frequency and nocturia. Most attention
      to OAB's impact on health-related quality of life (HRQL), however, has focused on
      urge incontinence. The objective of this study was to evaluate the burden of OAB,
      specifically urinary urgency and frequency on HRQL. METHODS: In the National
      Overactive Bladder Evaluation Program (NOBLE), a computer-assisted telephone
      interview survey was conducted to assess the prevalence of OAB in the United
      States. Based on interview responses, respondents were classified into three
      groups: continent OAB, incontinent OAB, and controls. To evaluate the HRQL impact
      of OAB, HRQL questionnaires were mailed to all respondents with OAB and age- and
      sex-matched controls as a performed nested case-control study. Continuous data
      were compared using Student's t tests and analysis of variance with post hoc
      pairwise comparisons; results were adjusted for age, sex, and comorbid
      conditions. Multivariable regressions were performed to assess the impact of each
      urinary variable on symptom bother and HRQL. RESULTS: A total of 919 participants
      responded to the questionnaires (52% response rate) with a mean age of 54.2 years
      (SD 16.4 years); 70.4% were female and 85% were white. Continent OAB participants
      comprised 24.8% of the sample, incontinent OAB 18.3%, and controls 56.9%. In each
      regression analysis, urinary urge intensity accounted for the greatest variance
      for increases in symptom bother and decreases in HRQL. CONCLUSIONS: The
      experience of urinary urgency has a significant negative effect on HRQL and
      increases symptom bother, an effect that, in this community sample, is greater
      than that of incontinence, frequency, or nocturia.

PMID- 15449638
TI  - Impact of anemia on hospitalization time, charges, and mortality in patients with
      heart failure.
AB  - OBJECTIVES: Although anemia is known to influence clinical outcomes in heart
      failure (HF) patients, little is known about its impact on economic outcomes. A
      retrospective analysis was performed to determine the impact of hemoglobin (Hb)
      level on hospital length of stay (LOS), total charges, and hospital mortality in
      HF patients. METHODS: Claims data were drawn from 21 teaching and nonteaching
      hospitals for patients hospitalized between October 1, 2000 and September 30,
      2001. The impact of Hb on LOS, charges, and hospital mortality was determined
      using multivariate analyses. Two-stage least squares regression methods were used
      to assess the potential endogeneity of the economic outcomes (LOS and total
      charges) and Hb level. RESULTS: Of the 8569 patients in the analysis, 40.2% had
      Hb < 12 g/dl and 73.8% were > or = 70 years of age. Hemoglobin had significant
      independent effects on all three outcomes. A 1 g/dl increase in Hb was associated
      with a 5.1% reduction in LOS (P < 0.001), a 4.3% decrease in charges (P < 0.001),
      and an 8.7% reduction in mortality risk (P < 0.001). The impact of Hb on all
      outcomes was greatest in younger HF patients. CONCLUSIONS: This analysis
      demonstrates that higher Hb is associated with reductions in LOS, charges, and
      mortality in hospitalized HF patients. Further clinical studies are necessary to
      validate the cost effectiveness of pharmacologic intervention in anemic HF
      patients and its impact on patient care.

PMID- 15449639
TI  - Cost-effectiveness analysis of bicalutamide (Casodex) for adjuvant treatment of
      early prostate cancer.
AB  - OBJECTIVES: To assess the cost-effectiveness of bicalutamide (Casodex) as
      adjuvant treatment in early prostate cancer (EPC). METHODS: A Markov state
      transition model was developed, using disease progression rates from a large (N =
      8113) clinical trial program comparing bicalutamide in addition to standard care
      with standard care alone. Utility scores for different disease stages were
      obtained from published reports. Costs of disease progression were obtained from
      a retrospective patient chart analysis in six Belgian centers (n = 60). The time
      horizon was 15 years and the analysis was conducted from the public payer
      perspective. RESULTS: The model showed good validity in predicting clinical
      outcomes. At a time horizon of 15 years, an incremental cost-effectiveness of
      27,059 euros/QALY was obtained. The main factors influencing conclusions included
      the time horizon, the duration of bicalutamide treatment, which was set at a
      maximum (5 years) in the base case, and possible differences in prognosis of
      metastatic cancer between comparators. Also the discounting of health effects
      significantly altered cost-effectiveness ratios. Many of these influences are
      inherently associated with any cost-effectiveness analysis related to treatment
      of early, slowly progressing malignancies because such an analysis requires a
      sufficient time horizon to include not only the treatment costs but its benefits
      as well. CONCLUSION: Based on the current data, bicalutamide appears to be a cost
      effective option for adjuvant treatment of EPC.

PMID- 15449640
TI  - Development of a parametric simulation model for forecasting goal-oriented
      treatment outcomes.
AB  - BACKGROUND: Treatment-to-goal (TTG) analyses are frequently used to predict
      guideline-directed population control rates for drug therapies based on mean
      efficacy data. Nevertheless, estimates are commonly inaccurate because
      variability in efficacy is not considered. A new methodology was developed to
      improve TTG forecasting. METHODS: Patient-level blood pressure (BP) lowering data
      sets, designed to simulate clinical trial results, were generated for testing
      from three underlying distributions: normal, lognormal, and beta. To emulate real
      world conditions where patient-level data are unavailable, two approaches were
      considered: parametric--simulated BP lowering data were generated using the mean
      and standard deviation of the test data sets; and point-estimate--BP lowering was
      uniformly assigned as the mean lowering. BP control (systolic BP < 140 and
      diastolic BP < 90 mmHg) was forecasted by subtracting values generated by these
      two methods from baseline BP values in untreated hypertensive patients (n = 2483)
      from the Third National Health and Nutrition Examination Survey. Estimated
      control rates were compared to analyses where the patient-level data sets were
      bootstrapped. RESULTS: We assumed mean (+/- SD) BP lowering of 20 (12) mmHg
      systolic and 14 (7) mmHg diastolic. Parametric method predicted a BP control rate
      of 66.9% [95% confidence interval (CI) 65.7-67.9], similar to the bootstrapping
      approach (67.3%, 95% CI 65.9-68.8). The control rate projected based on the point
      estimate method was 75.5%. The point-estimate method frequently led to
      substantially different results under a wide range of model assumptions.
      CONCLUSIONS: A new parametric-based forecasting method, which addresses
      underlying variability, improves on estimates based on mean efficacy only. In the
      absence of patient-level data, this method is generalizable to different
      therapeutic areas.

PMID- 15449641
TI  - Estimating a preference-based single index for the Impact of Weight on Quality of
      Life-Lite (IWQOL-Lite) instrument from the SF-6D.
AB  - OBJECTIVE: To facilitate economic evaluations of interventions for treating
      obesity, we estimated a preference-based single index for the Impact of Weight on
      Quality of Life-Lite (IWQOL-lite) instrument by mapping it onto the SF-6D
      preference-based index. METHODS: A heterogeneous sample of 1972 individuals,
      composed of community volunteers and participants in weight loss programs,
      clinical trials, and gastric bypass studies, completed the IWQOL-lite, an obesity
      specific measure of health-related quality of life (HRQOL), and the SF-36, a
      generic measure of HRQOL converted into the preference-based SF-6D. Models of the
      relationship between the IWQOL-lite and SF-6D of increasing complexity were
      estimated by regression analyses. RESULTS: The best fitting model for predicting
      SF-6D index scores entered levels for each item as independent variables (R2
      =0.530 in the cross-validation sample, with a mean absolute error of 0.0976).
      This model (1) makes fewer assumptions than those using total score, dimension
      scores or item scores as dependent variables and (2) provides a robust unbiased
      estimate of a preference-based index from IWQOL-Lite data where a preference
      based measure was not used. The addition of age and body mass index (BMI) led to
      a slight improvement in the model. CONCLUSIONS: It is possible to facilitate
      economic evaluations using results obtained from disease-specific instruments
      using this approach. A weakness of this approach is that there may be aspects of
      the condition that have not been properly reflected in the SF-6D index. It is,
      however, useful when a preference-based measure has not been administered and
      when it would be impractical to conduct a full valuation survey.

PMID- 15449642
TI  - The construct and concurrent validity of the EQ-5D in a renal transplant
      population.
AB  - OBJECTIVES: Cost-utility analysis in renal transplant populations requires the
      use of a generic instrument for health status measurement that generates a single
      value for health. Such instruments should be widely applicable in diverse patient
      populations and their validity should be established. The aim of this study was
      to explore the validity of the EQ-5D in renal transplant patients. METHODS: The
      EQ-5D was compared with the Short-Form 36 Health Survey (SF-36), the modified
      transplant symptom occurrence and symptom distress (MTSOSD) scale, the short-form
      Beck Depression Inventory (BDI), and the State Trait Anxiety Inventory (STAI).
      Construct and concurrent validity were tested on cross-sectional data of 350
      patients. RESULTS: Construct validity is good for some but not all EQ-5D
      dimensions, and the EQ-5D discriminates well among groups of patients with
      different health states according to the SF-36, MTSOSD scale, BDI, and STAI and
      between patients and the general public. Concurrent validity is good, as shown by
      the correspondence of EQ-5D and SF-36 results. CONCLUSION: It is concluded that
      the EQ-5D is a valid instrument for the measurement of health status in renal
      transplant patients.

PMID- 15449643
TI  - Concerns regarding the ISPOR Code of Ethics for Researchers.

PMID- 15449644
TI  - Study on enteric parasitosis and nutritional status of school children in remote
      hilly areas in Nepal.
AB  - We examined the effect of enteric parasitosis on nutritional status of school
      children in remote hilly areas in Nepal. A total of 325 school children aged 6 to
      19 years (boys: 214; girls: 111) who provided both blood and stool samples were
      included. The height (Ht) (cm), weight (Wt) (kg), age, sex, ethnic of each child
      were recorded. Fecal samples were examined by direct smear method in duplicate.
      The blood hemoglobin (Hb) was estimated by Sahli's method in the field (Nepal)
      whereas the serum protein (Prot), albumin (Alb), Alb/globulin ratio (A/G), serum
      glutamate pyruvate transaminase (SGPT), cholesterol (Chol), triglycerides (Trig),
      and serum iron (SI) were measured in Japan. Of the total, 201 (61.8%) had enteric
      parasites, predominantly the soil transmitted helminths. Ascaris lumbricoides was
      the most common parasite detected (72.6%) followed by hookworm (16.2%) and
      others. Protozoan infections were very low (<6.0%). Of the total 201 parasite
      positive children, 15.4% had multiple infections. No significant differences in
      Ht and Wt in parasite positive and negative boys and girls of both age groups (<
      11 and 11-19 years) were observed (P>0.05). Overall, no significant differences
      in levels of Hb, Prot, A/G, SGPT, Chol, Trig and SI in the parasite positive and
      negative children were observed (P>0. 05) but in Alb level (P<0.05). When, the
      levels of these parameters were compared in the age groups of <11 and 11-19
      years, similar findings were observed in both the age groups. But, in the age
      group of 11-19 years, a significant difference was observed in Trig level
      (P<0.05). No differences were found in the levels of these parameters in the
      parasitic positive and negative children belonging to Dalits and different ethnic
      namely, Indo-Aryan and Tibeto-Burman, respectively.

PMID- 15449645
TI  - Epidemiological survey of intestinal parasitic infections of diarrhoeal patients
      in Nepal and Lao PDR.
AB  - Intestinal parasitological survey was conducted to clarify the distribution of
      intestinal parasites in Nepal and Lao Peoples' Democratic Republic (Lao PDR) from
      2001 to 2003. A total of 401 diarrheal fecal specimens were collected from
      patients aged one to 75 years (250 from Nepal and 151 from Lao PDR). The
      specimens were examined using the formalin-ether sedimentation (FES) and sucrose
      centrifugal flotation (SCF) techniques. Nine species (3 Nematoda, 1 Cestoda, and
      5 Protozoa) of parasites were recovered from Nepal, whereas seven species (3
      Nematoda, 1 Trematoda, and 3 Protozoa) from Lao PDR. Of the parasites detected,
      (14.4%) was the most common in Nepal, and was Opisthorchis viverrini (29.8%) in
      Lao PDR. Infection rates were markedly different among age groups in both
      countries; higher rates were observed in age groups of 10-29 years than in 0-9
      years group. Scanning electron microscopic observation revealed that trematoda
      eggs recovered from Lao PDR were identified as O. viverrini, which could not be
      done by a light microscope.

PMID- 15449646
TI  - Status of serum ferritin and folate levels amongst young women in a rural
      community of Haryana, India.
AB  - A community based cross sectional study was conducted amongst young married non
      pregnant women aged 18 years or more from six randomly selected villages in
      Ballabhgarh block, district Faridabad, Haryana state. Data was collected on socio
      demographic profile and obstetric parameters utilizing a pre-tested semi
      structured questionnaire. The non-pregnancy status of the women was confirmed by
      inquiring about the last menstrual period. Serum ferritin and folate levels were
      assessed utilizing the ELISA and the RIA method, respectively Serum ferritin and
      folate levels less than 15.0 and 3 ng/ml were considered as indicator of poor
      iron and folic acid stores, respectively. The dietary intake of iron, folic acid
      and calories was assessed utilizing the 24-hour dietary recall methodology.
      Almost 63.8 and 27.7 % of the women had poor serum ferritin and folate levels.
      The mean dietary intake of iron, folic acid and calories was 14.8+/-7.7 mg,
      49.2+/-20.1 microg, and 1564+/-411 kcal, respectively. There was an inadequate
      intake of food as revealed by their calorie intake that was 83.4% of the
      recommended dietary allowances. Only 6.9 and 7.8 % of the women were consuming
      iron and folic acid more than 75.0 % of the recommeded dietary allowances (RDA)
      Women with dietary intake of calories less than 50.0 % of the RDA had a lower
      serum ferritin level compared to the women who had a higher calorie intake. It
      was also revealed that there was a decreasing trend in serum folate levels with
      poor socio-economic status. Young rural women had poor serum ferritin and folate
      levels in the community studied, possibly due to poor dietary intake of food and
      thereby iron and folic acid. Distribution of iron and folic acid tablets may be
      recommended to young women of reproductive age group.

PMID- 15449647
TI  - Detection of diarrheagenic viruses from diarrheal fecal samples collected from
      children in Kathmandu, Nepal.
AB  - Diarrhea causing viruses (Rotavirus. Adenovirus and Norovirus) were investigated
      in diarrheal fecal samples collected from children in Kathmandu, Nepal in Janury
      2004 using both real time PCR and immuno-chromatogaphic techniques. Of the total
      12 diarrheal samples investigated, 8 (66.7%) were positive for Rotavirus, 1
      (8.3%) was positive for Adenovirus and none was positive for Norovirus (Norwalk
      like virus). The Adenovirus positive sample was also positive for Rotavirus.
      Similar results were obtained by immuno-chromatographic technique. All of
      Rotavirus detected belonged to Group-A. Results indicated that immuno
      chromatographic technique was equally good in the detection of diarrhea causing
      viruses in fecal samples. Furthermore, it was simple, cost-effective and less
      time consuming (15 minutes) compared with the PCR. Immuno-chromatographic
      technique, therefore, appeared to be useful for rapid diagnosis of viral
      gastroenteritis in developing countries like Nepal.

PMID- 15449648
TI  - Transbronchial needle aspiration in the diagnosis of respiratory diseases.
AB  - Thirty-three patients were subjected to transbronchial needle aspiration during
      the routine diagnostic bronchoscopy. Of the 17 patients with submucosal diseases,
      Transbronchial needle aspiration (TBNA) had a yield of 88.2% as against 81.2% for
      bronchial biopsies, 54.5% for bronchial brush smears and 41.1% for bronchial
      aspirates. TBNA also had a good yield in endobronchially visible growths. Nine
      patients had mediastinal or hilar lymph nodes as evident in contrast enhanced CT
      scans. TBNA was attempted from eight lymph node sites in six patients with
      bronchogenic carcinoma and was positive for malignant cells from four of these
      sites, while normal lymphoid cells were obtained from the other four sites. TBNA
      could also diagnose the disease from the left hilar lymph node in one patient
      with sarcoidosis, an extra tracheal bronchogenic carcinoma in another patient and
      an extra bronchial metastasis in yet another patient where conventional
      bronchoscopic techniques failed. TBNA was found to be a safe, cost effective and
      valuable diagnostic tool in the diagnosis of pulmonary diseases.

PMID- 15449649
TI  - Intestinal parasites and intra familial incidence in a low socio-economic area of
      Chandigarh (North India).
AB  - A total of 550 stool samples were collected from a low socio economic population
      of Chandigarh (North India) and examined macroscopically and microscopically, to
      determine the prevalence of intestinal parasitic infections and their familial
      incidence. The overall prevalence rate was 19.3%. Ascaris lumbricoides and
      Giardia lamblia were the commonest, affecting 51 (9.3%) and 33 (6.0%),
      respectively. In 17 (22.7%) families the same parasite was observed to infect
      multiple family members, which included A.lumbricoides (in 9 families), G.
      lamblia (in 7 families) and H. nana (in 1 family). The results of present study
      indicate that there is a high prevalence of parasitic infection in the community
      where personal hygiene and sanitary conditions are poor and may be one of the
      contributing factors for transmission within the families. Intervention
      strategies including health education program should be designed and implemented
      to control parasitic infections.

PMID- 15449650
TI  - The clinical study of chronic pancreatitis.
AB  - Chronic pancreatitis is a relentlessly progressive fibro inflammatory process
      which may eventually lead to pancreatic insufficiency. This study is done to
      review the various treatments for chronic pancreatitis and to analyze the
      clinical features, different etiological factors, comparing different clinical
      trials in India as well as western countries. One hundred and eight patients with
      the diagnosis of chronic pancreatitis were included in this study from January
      1996 to June 1999. In this present series, most of the patients presented in the
      3rd and 4th decades of life. The most common presentation was recurrent episodes
      of pain in the epigastrium radiating to the back. Most patients are non-alcoholic
      and the etiological factor in this group may be attributed to the nutritional,
      idiopathic, hereditary etc, though the single most common etiological factor
      seemed to be alcohol. The most specific investigation to detect the presence of
      pancreatic calculi, pseudo cysts, and duct dilatation was ultrasonography. Among
      the drugs, antioxidant therapy found to have effective role in the conservative
      management. Puestow's lateral pancreaticojejunostomy is most commonly performed
      surgery which has good results.

PMID- 15449651
TI  - Study of cases of hypertension admitted at Nepal Medical College Teaching
      Hospital.
AB  - Hundred cases of hypertension admitted to medical ward at Nepal Medical College
      and Teaching Hospital were studied and analysed. They constituted 9.4% of the
      total admitted patients in the medical ward. Association of hypertension with
      other diseases is highlighted. Thirty two percent of these hypertensives were
      diabetic and 22.0% of hypertensives also had Chronic obstructive airway disease
      (COAD). Different types of complications of hypertension seen in the studied
      subjects are mentioned. Only 19.0% of hypertensives had their blood pressure
      controlled and the rest were uncontrolled hypertensives.

PMID- 15449652
TI  - Effect of temperature on phagocytic activity of neutrophils.
AB  - The effect of temperature on phagocytic activity of neutrophils has been
      evaluated. Freshly collected heparinised blood samples from young healthy
      volunteers were incubated with heat killed Staphylococcus aureus at 37 degrees C,
      38 degrees C, 39 degrees C and 40 degrees C for 20 minutes. Some of the
      neutrophils engulfed some heat killed bacteria. Then the blood smears were
      prepared and stained by Leishman's stain. Engulfed bacteria within the
      neutrophils stained intensely were observed and counted to find out the
      phagocytic index and avidity index of the neutrophils. It was found that
      phagocytic index increased significantly at 38 degrees C and 39 degrees C in
      comparison to that of at 37 degrees C but did not show significant increase when
      incubated at 40 degrees C. It seems that contractile elements responsible for the
      movement of the neutrophils through the formation of pseudopod is more activated
      at higher temperature (38 degrees C and 39 degrees C) in comparison to that of at
      normal body temperature (37 degrees C). Temperature higher than 39 degrees C may
      cause impairment in enzyme function responsible for assembly and disassembly of
      actin and myosin filaments in the cell causing decreased movement and decreased
      rate of formation of psudopod resulting in decreased phagocytic activity.

PMID- 15449653
TI  - Influence of radish consumption on urinary calcium oxalate excretion.
AB  - The study was undertaken to observe the effect of radish on urinary calcium
      oxalate excretion. Early morning midstream urine (MSU) samples collected from 36
      subjects were analyzed continuously for a period of 14 days for the presence of
      calcium oxalate crystals. Of these, 21 cases were of renal stone and 15 were
      normal subjects. The subjects were advised to consume self-selected diet for a
      week and radish containing diet along with their self-selected diet for
      consecutive week. The study reveals that radish containing diet caused increased
      excretion of calcium oxalate compared to the self-selected diet and the crystals
      count in the urine were significantly higher in both genders. The difference
      between males and females was found to be insignificant indicating that there is
      no gender biasness on urinary calcium oxalate excretion. This study is first of
      its kind as literature search reveals no such study have been carried out
      earlier.

PMID- 15449654
TI  - Study on koilocytosis, X-chromatin and HSV-2 in cervical smears in Nepal.
AB  - A total of 1,106 cervical smears were studied during a one year period from Feb
      1999 to Feb 2000. Majority of the lesions were Inflammatory smears constituting
      91.0%, Cervical intraepithelial neoplasia [CIN] and Squamous cell carcinoma [SCC]
      cervix constituted 8.0% and 1.0% respectively. The percentage of different grades
      of CIN being CIN I 85.0%, CIN II 9.0% and CIN III 6.0%. Thirty cases were taken
      as a study group. The commonest age group for CIN was 31-40 years 80.0% and for
      carcinoma cervix above 50 years 63.0%. The most common risk factors were marriage
      before 20 years of age 80.0% and a low socio-economic status 70.0%. The common
      presenting feature in CIN was pain lower abdomen 88.0%, followed by whitish
      discharge per vagina 60.0%. Similarly in carcinoma cervix pain lower abdomen
      80.0% followed by weight loss 60.0% were the common presenting symptoms.
      Koilocytic change was seen in 42.1% of the cases of CIN I. The incidence of X
      chromatin positivity gradually decreased as the lesion advanced, the p-value
      between CIN I and CIN II [p=<0.02], CIN I and CIN III [0=0.00] and between CIN
      III and Carcinoma cervix [p=<0.004] being significant. An association with Herpes
      simplex virus-2 [HSV-2] was seen in 11.0% cases of CIN I, 33.0% cases of CIN IIl
      and 40.0% cases of carcinoma cervix with a gradual rising antibody titre of 1:2
      in CIN I, 1:7 in CIN III and 1:7 to 1:9 in carcinoma cervix respectively.

PMID- 15449655
TI  - Study on urinary bladder stone cases at Okhaldhunga Hospital, Nepal. 1988--1994.
AB  - A retrospective study on urinary bladder stones among the patients seeking
      treatment in Okhaldunga Hospital was carried out for six calendar years from 1988
      to 1994. Forty-six cases of bladder stones were identified during that period.
      Among them, 43 patients' records were studied (93.0%) in subsequent analysis.
      Ninety-seven percent were male with mean age 11.53+/-6.9 years. The number of
      children are significantly higher in 0-9 years of age (p<0.01). The symptoms
      lasted more than 2 years with the most common presenting symptoms dysuria (86.0%)
      and poor flow of urine (41.8%). The average hospital stay was 8.7 days. The
      majority of cases (78.5%) had undergone cystolithotomy without any complications.
      The study also showed that the majority (97.0%) of urinary bladder stone cases
      were successfully managed at a rural hospital like Okhaldhunga.

PMID- 15449656
TI  - Caesarean delivery at Nepal Medical College Teaching Hospital, Kathmandu, Nepal.
AB  - This is a retrospective study conducted in Department of Obstetrics and
      Gynaecology. The study includes all delivery in Nepal Medical College Teaching
      Hospital (NMCTH) from March 09, 1997 to April 13, 2002. The objective of this
      study is to find out the incidence, indications, complications and fetal outcome
      in all caesarean deliveries. All files of caesarean deliveries were obtained from
      hospital records and studied. Data were collected and analysed. In 5 years period
      total deliveries in NMCTH were 1727. There were 163 cases of caesarean delivery
      with caesarean delivery rate 9.4%. Slow progression of labour, previous CS, fetal
      distress and breech presentation were the first four common indications of
      caesarean delivery in NMCTH. Regarding complication and caesarean delivery the
      incidence of complications was 23.9% of all deliveries. We found postpartum
      haemorrhage (n=27) 69.2% of all cases with complications. Few cases of wound
      infection and UTI also noticed in this study. Total babies born were 165 with 2
      sets of twins. Three babies had APGAR score less than 3 and there were 2 neonatal
      death after caesarean delivery.

PMID- 15449657
TI  - A comparative study of cost analysis of antibiotic use in clinics and hospitals
      of Kathmandu Valley, Nepal.
AB  - Excessive use of antibiotics (AB) has resulted in resistant strains of
      microorganisms, adverse drug reactions (ADR's) and cross-resistance. This study
      showed that AB are being used indiscriminately. We carried out a retrospective
      comparative cost analysis study on the use of AB in clinics and hospitals on a
      larger population by analyzing 1200 prescriptions of various diseases containing
      AB and cost effectiveness was compared. It was found that surgeons prescribed
      costliest AB whereas physicians used cheapest AB. Overall the costliest treatment
      was prescribed by gynecologists of hospitals, and the most economical treatment
      was prescribed by pediatricians in the clinics.

PMID- 15449658
TI  - Evidence for HIV-2 infection in Nepal.
AB  - Assessment of the presence and prevalence of HIV-2 antibodies in patients
      attending the Universal College of Medical Sciences Teaching Hospital,
      Bhairahawa, western Nepal was done. A total of 1534 patients sera were screened
      for the presence of HIV-1 and HIV-2 antibodies from March 2000 to May 2003. A
      total of 3 (0.2%) patients were found to be sero-positive for HIV-2 antibodies.
      Out of the above three patients, 1 (0.1%) was infected with HIV-2 only and the
      remaining 2 (0.1%) were infected with HIV-1 and HIV-2 both. This evidence of the
      presence of HIV-2 presence implicates serious outcomes as HIV-2 has not been
      reported from hospital patients in Nepal.

PMID- 15449659
TI  - Bilateral sternales in relation to body of sternum.
AB  - The sternalis muscle on the manubrium sterni and its communication with
      sternocleidomastoid has been reported by many workers as unilateral or bilateral
      in both the sexes. The present report deals with bilateral sternales below the
      angle of sternum in a male cadaver during routine dissection. The proximal
      attachment of the muscle was from the manubriosternal joint on either side, right
      being broader than left and was found to be overlapping the lateral part of
      sternum and adjoining pectoralis major muscle. The muscle was running downwards
      and laterally and was attached on the cartilage of 6th and 7th ribs appearing to
      be continuous with rectus abdominis muscle. The muscle was found to be innervated
      by branches of the corresponding intercostal nerves of these spaces. The
      sternalis if present could be used for reconstructive surgical operations on the
      breast.

PMID- 15449660
TI  - Multisystem involvement of microfilaria in a HIV positive patient.
AB  - A 35-year-old HIV positive male presented with dyspnoea and chest pain was
      diagnosed having acute pericardial and pleural effusion. Microfilaria was
      detected from blood as well as from the pericardial and pleural fluid and from
      urine. CD4 count was 123 cells microl. The patient was receiving treatment with
      antiretroviral therapy and Cotrimoxazole for last 4 months. The patient had no
      opportunistic infection and no symptoms suggestive of filarial infection in the
      past. This is for the first time we are reporting high microfilarial load
      (1000/ml) from blood in HIV positive patient, where microfilaria was also
      demonstrated from the pericardial and pleural fluid and from urine.

PMID- 15449661
TI  - A blackening lady--case report.
AB  - A 40 year old lady presented with the classical clinical features of Addison's
      disease which on further investigations with an ultrasound abdomen showed a right
      suprarenal mass. This was subjected to a fine needle aspiration which revealed
      pus which on culture grew Klebsiella pneumoniae. Patient responded well to
      steroids and antibiotics. To the best of our knowledge this is the first report
      of Klebsiella pneumoniae in association with Addison's disease.

PMID- 15449662
TI  - [Effects of hydrosulfide balneotherapy on microcirculation in arterial
      hypertension].

PMID- 15449663
TI  - [Normobaric hypoxia, ozone therapy and respiratory exercise with expiratory
      resistance in rehabilitation of patients with chronic bronchitis and bronchial
      asthma].

PMID- 15449664
TI  - [Responses to weather factors in healthy residents of low-mountain regions].
AB  - External respiration function, surface-active properties of pulmonary surfactant,
      autonomic nervous system tonicity, intensity of lipid peroxidation and activity
      of antioxidant defence enzymes activity were studied in 22 healthy subjects
      having no adverse reactions to weather changes. It is shown that the organism of
      healthy subjects respond to unfavourable weather conditions with activation of
      the antioxidant enzyme and sympathetic effects of the vegetative nervous system.

PMID- 15449665
TI  - [Possibilities of immunomodulation in patients with chronic bronchitis during
      physiotherapeutic impacts on the thymic area].
AB  - Immune effects of galvanic current (GC) and ultrasound (US) applied on the thymic
      area were studied in 66 patients with chronic bronchitis (CB) on rehabilitation
      treatment. 64 control CB patients either receive an immunomodulating drug
      thymalin or were treated without immunomodulation. It was found that GC and US
      are effective in disorders of cellular immunity and result in closer interaction
      between separate components of immune system. The immunomodulating effect of GC
      and US was comparable with that of thymalin.

PMID- 15449666
TI  - [Drinking mineral waters in rehabilitation of cancer patients].
AB  - Three hundred postmastectomy breast cancer patients and 150 patients after
      gastric resection for cancer have received spa treatment. It was found that a
      course intake of mineral water in both groups improved immune status: raised
      significantly the levels of T- and B-lymphocytes and their functional activity,
      reduced blood levels of IgG and CIC providing the phenomenon of immunological
      enhancement of tumor antigens. Incidence rate of postgastroresection disorders
      after the spa treatment fell 3.8 times, performance raised 3.1 times. The number
      of breast cancer recurrences decreased by 20%.

PMID- 15449667
TI  - [Antimicrobial properties of drinking mineral water in experiment].
AB  - We studied in vitro effects of mineral waters Ust-Kachkinskaya and Obukhovskaya
      on survival of gram-negative and gram-positive bacteria, candida fungi and on
      their sensitivity to antimicrobial drugs. The above mineral waters deteriorate
      viability of opportunistic bacterial and fungal flora and raise its sensitivity
      to antibiotics.

PMID- 15449668
TI  - [Characteristics of microflora isolated in chronic adnexitides and effects of
      balneotherapy on biological properties of microorganisms in experimental and
      clinical conditions].
AB  - The study of species and biology of microflora isolated from 42 patients with
      chronic adnexitides has detected a wide spectrum of pathological agents among
      which both aerobic and anaerobic microorganisms were encountered. The isolated
      cultures were examined for ability to inactivate lysozyme, complement and
      lactoferrin. The experiments have established changes in biological properties of
      the microorganisms in response to use of mud and salty brine therapy. Clinical
      investigations demonstrate the ability of balneotherapy to restore normal flora,
      to reduce contamination with opportunistic microflora and suppress biological,
      including persistent, properties of microorganisms in females with chronic
      adnexitides. Positive effects of balneotherapy seem to base, primarily, on this
      ability.

PMID- 15449669
TI  - [Electrophoresis of sulphide mud extract in combined therapy of chronic
      inflammatory diseases of uterine appendages (an experimental and clinical
      study)].
AB  - On the original experimental model of chronic inflammation of the ovaries and
      oviducts in white rats it was established that electrophoresis of 1% esobel
      solution prevents an increase in the specific volume of interstitial connective
      tissue, development of fibrosclerotic alterations and adhesive process.
      Peloidophysiotherapy normalizes growth and atresia of the ovarian follicular
      system. Thus, electrophoresis of 1% esobel solution is highly effective in
      combined treatment of chronic inflammatory diseases of the uterine appendages.

PMID- 15449670
TI  - [Using combined magnetotherapy in patients with acne].
AB  - Laser Doppler flowmetry discovered microcirculatory disorders in acne patients.
      Affected are arterioles as well as capillaries and venules. Combination of
      magnetotherapy with medication improves microcirculation in acne patients. More
      marked positive changes occurred in the microcirculatory system due to combined
      treatment compared to medication therapy only. Thus, laser Doppler flowmetry is a
      new, noninvasive method of assessing microcirculation in acne patients and can
      serve an objective criterion of treatment efficacy.

PMID- 15449671
TI  - [Effects of sulfate mineral water and vetoron on the rate of radiation-induced
      aneuplodia in the bone marrow cells of rats].
AB  - Experiments on non-inbred male rats have found that pretreatment with drinking
      sulfate mineral water and veteron reduced incidence of radiation-induced
      aneuplodia in bone marrow cells. The proportion of cells with normal number of
      chromosomes went up.

PMID- 15449672
TI  - [Bicarbonate calcium mineral water with carbon dioxide in rehabilitation of
      children with dismetabolic nephropathies complicated by renal inflammation].
AB  - A renal function was studied in children with dismetabolic nephropathy and renal
      inflammation before and after spa treatment with low-mineral water from the
      spring "Gornovodnoye". Drinking the water resulted in intensification of 24-h
      diuresis in increasing proportion of sodium and chlorine ions concentrations and
      decreasing proportion of calcium and magnesium ions concentrations. A membrane
      stabilizing action of Gornovodnenskaya mineral water reduced oxaluria and
      uraturia. An effective scheme of balneotherapy is proposed.

PMID- 15449673
TI  - [Ultraphonophoresis and photophoresis of chondroxide ointment in combined
      treatment of mandibular fractures].
AB  - Efficacy of mandibular fractures treatment with laser irradiation, ultrasound
      therapy, photophoresis and ultraphonophoresis of 5% chondroxide oitment in 108
      patients with mandibular fractures was studied. Physicopharmacological and
      clinical investigations showed perspectiveness of using photophoresis and
      ultraphonophoresis of chondroxide in maxillofacial traumatology for treatment of
      mandibular fractures.

PMID- 15449674
TI  - [Quality of life as a research field in physiotherapy].

PMID- 15449675
TI  - [Organisation of work in sanatorium and health resort institutions of the Ural
      Federal Territory for the promotion of health of working population of Russia].

PMID- 15449676
TI  - [Whole-grain bread in therapeutic diets of health resorts and sanatoria].

PMID- 15449677
TI  - [The 100th anniversary of the II All-Russia congress on climatology, hydrogeology
      and balneology in the Kavkaz Mineral Waters].

PMID- 15449678
TI  - [State and outlooks of using therapeutic physical factors in oncology].

PMID- 15449679
TI  - [Pathologic anatomy of hard drinking and alcoholism].
AB  - The analysis of 826 autopsies is presented. 654 persons in their life abused
      alcohol but refused treatment; they were considered as hard drinkers. 172 persons
      were repeatedly treated for alcoholism and were included into the group of
      alcoholics. The control group consisted of persons who had not abused alcohol.
      Morphological and morphometric methods were used. It is shown that chronic
      alcoholic intoxication involves all internal organs with the same trend in
      pathological processes in hard drinkers and alcoholics. There was progressing
      alteration of microcirculatory bed, fat degeneration of parenchymatous organs,
      atrophic and sclerotic processes, primarily in the liver, lungs, heart and brain.
      While in hard drinking pathological processes can be considered reversible and
      well compensated, in alcoholism the degree of organ damage makes these lesions
      irreversible. It is suggested that less severe organ damage in hard drinking is
      due to the effect of ethanol while grave atrophic and sclerotic processes as well
      as psychic dependence on alcohol are due to acetaldehyde. The key point in
      alcohol abuse is hard drinking (or preclinical stage of alcoholism) as there is
      neither psychic no physical dependence on alcohol and organ alterations are
      reversible under adequate treatment. The treatment should be performed first of
      all of the liver to enhance its basal metabolism.

PMID- 15449680
TI  - [Structural alterations in the human brain in acute alcohol intoxication].
AB  - Various regions of the brain were studied in 14 patients who suddenly died and in
      20 patients who died from ethanol intoxication. Severe circulatory disorders with
      pronounced vascular pathology, blood diseases, degenerative and necrotic
      neurocytic changes were shown to develop in ethanol intoxication. The area of
      neurocytes in the hemispheric cortex, thalamus, and cerebellum reduced due to the
      death of some of them. In the medulla, they were found to be more resistant to
      ethanol. The diameter of capillaries in the studied regions of the brain
      decreased due to the fall in cerebral arterial tonicity, the number of these
      vessels on the standard area increased, which is due to the compensatory
      dilatation of reserve capillaries.

PMID- 15449681
TI  - [Human epiphyseal concrements in schizophrenia].
AB  - The epiphysis is a gland containing firm extracellular bodies (brain sand) the
      number of which increases with age. Microscopy and roentgen microtomography
      showed that in some cases of schizophrenia the amount of brain sand decreases. In
      parallel, cytoplasm of pinealocytes appears to contain concrements of a new type-
      irregular hollow spheres of 0.1-1.5 microm in size. They may contain fluoride.
      Typical hydroxyapatite retaining organic stroma may dissolve starting from the
      center both in health and schizophrenia.

PMID- 15449682
TI  - [Features of tanatogenesis and extensiveness of myocardial infarction depending
      on severity of atherosclerotic stenosis of the coronary arteries].
AB  - 142 fatal cases of acute myocardial infarction (AMI) are analyzed. In 56% cases
      the surface of AMI exceeded 50% of the working surface of the left ventricle and
      patients died, as a rule, during the first week of the disease of cardiogenic
      shock or progressing heart failure. In cases of a small AMI (up to 30% of working
      surface of the left ventricle, 25% cases) the frequent cause of death was
      external cardiorrhexis. It is emphasized that the size of AMI is not always
      determined by severity of stenosing atherosclerosis in the coronary arteries
      since isolated stenosis of one branch can also provoke a large AMI. The results
      are in favour of more active use of prophylactic surgical (including
      endovascular) treatment of ishemic heart disease before the development of a
      large AMI.

PMID- 15449683
TI  - [Pathomorphogenesis of cytomegalovirus lungs lesions in HIV infection].
AB  - Pathomorphologic characteristics of cytomegalovirus (CMV) lung damage in 18
      patients who died of HIV infection are outlined. The following variants of lung
      lesions are distinguished: 1) CMV transformation of the cells in the respiratory
      compartments and tracts; 2) pneumonias with development of caverns with CMV
      transformed cells; 3) productive CMV alveolitis with granuloma formation; 4)
      pulmonary fibrosis and "adenomatosis" associated with CMV infection; 5) CMV
      transformed cells in secondary lesions--tumours and infections. Heterogeneous
      number and distribution of CMV cells at early stages, tumours and purulent foci
      were documented in CMV infections of the lungs.

PMID- 15449684
TI  - [Endocrine cells of rectal epithelium in health, in nonspecific ulcerative
      colitis and irritable colon syndrome in the treatment with prednisolone and
      salofalk and in the absence of treatment].
AB  - The arrangement and ultrastructure of rectal intraepithelial endocrine cells in
      health, in nonspecific ulcerative colitis (NSUC) and in irritable colon syndrome
      (ICS) were studied with light and electron microscopy. An increase of the amount
      of these cells was registered at the initial stages of inflammation, whereas
      chronic and destructive states were accompanied by the cells decrease. A decrease
      of endocrine cells number in (NSUC) was pronounced more than in ICS. Compared to
      prednisolone, the treatment with salofalk produced a more positive effect on
      endocrine cells reproduction within the rectal lining. The endocrine cells
      ultrastructural changes found by the authors in ulcerative colitis and irritable
      colon showed similarity to those in other colon diseases.

PMID- 15449685
TI  - [Proliferation of fat cells in lipomas].
AB  - Common lipomas and destructive ones (intramuscular, infiltrating, necrotizing and
      destroying surrounding tissues) were studied in 9 patients electron
      microscopically and radioautographically. The adequacy of necrotizing processes
      and regeneration was observed: normal fat tissue-lipoma-destructive lipoma. In
      the latter besides pronounced destruction of tissue (adipocytes, vessels, muscles
      at the border with tumour), there was accelerated differentiation of
      preadipocytes from the cells-precursors (fibroblasts and undifferentiated cells
      of the vascular wall), hypertrophy of preadipocytes (their size and number of
      nuclei increase) and their proliferation. The process of malignant transformation
      in a destructive lipoma may be so much pronounced that DNA synthesis may be
      observed in the mature lipocyte (this has not been described so far).

PMID- 15449686
TI  - [Morphological changes in immunogenesis organs in transplantation of Guerin
      carcinoma to the spleen].
AB  - The study was made in 30 male Wistar rats (b.m. 110+/-10 g) with transplanted
      Guerin carcinoma to their spleen. Morphological changes in the tumour, spleen,
      thymus and mesenteric lymph nodes on tumour growth day 7, 10, 14, 18, 22, 25 were
      studied. The elaborated experimental model of tumour growth in the spleen allowed
      to detect tumor-specific changes in organs of immunogenesis as well as the
      dynamics of their development. The findings show possibility of renewal of both
      cellular content in the tumour-activation of proliferation, and in tissue of the
      spleen-blast transformation with predominance of lymphoblasts. Morphologic
      changes in the thymus and regional lymph nodes are different this meaning that
      changes in the organs of immunogenesis are not of a systemic character, their
      reaction to the presence of tumour in organism is not always the same and has its
      own features.

PMID- 15449687
TI  - [Affection of the central nervous system in Wegener's granulomatosis].
AB  - A case of a lesion of the central nervous system in Wegener's granulomatosis with
      neuritis of craniocerebral nerves, granulomas, vasculitis and foci of ishemic
      necrosis and hemorrhages in the brain tissue is reported. Diagnosis of Wegener's
      granulomatosis in a female aged 48 years was confirmed morphologically and by
      detection of specific antibodies. In spite of prednisolone (20 mg/day) and
      cyclophosphamide treatment (200 mg per week), hemiplegia, aphasia appeared which
      progressed and resulted in a death of the patient. Histologically lesions in many
      organs were found: middle ear, lungs, kidneys, brain, destructive vasculitis,
      necrotic foci and polymorphic lung granulomas, fibrosing alveolitis,
      polymorphocellular granulomas, multiple infarctions in the kidneys,
      endothrombovasculitis, necrotic foci and granulomas with glial reaction in the
      brain tissue.

PMID- 15449688
TI  - [Combination of pulmonary lymphangioleiomyomatosis (LAM) with angiomyolipoma
      (AML) of the kidney and multilocular cystic nephroma].
AB  - A rare case of pulmonary LAM in combination with AML and multilocular cystic
      nephroma of the kidney in a 18-year-old female is described. Granules of the
      melanosomic type in AML, HMB-45 antigen and steroid receptors expression in LAM
      and AML were observed.

PMID- 15449689
TI  - [Family myxoma of the heart with metachronic multiple growth].
AB  - A case of familial heart myxoma in 4 members of one family combined with myxomic
      (hamartomatous) syndrome is reported. The tumor in a proband was characterized
      with a multiple growth in various heart chambers. Five operations were made in
      the proband for 16 years and seven myxomas of different locations were removed.
      Myxomas originating from the endocardium of the interatrial septum oval hole were
      removed in 3 members of his family. The case confirms the conception of heart
      myxoma origin from endothelial hamartia of the endocardium.

PMID- 15449690
TI  - [Histiocytic sarcoma from phagocyting histiocytes].
AB  - Histiocytic sarcoma consisting of phagocyting histiocytes is a rare variant of
      histiocytic sarcoma. It is hard to detect because of its similarity with large
      cell lymphomas, in particular with anaplastic large cell lymphoma. Histological
      and immunohistochemical findings are presented. Differential diagnosis with
      tumours of hematopoietic and non-hematopoietic nature is described.

PMID- 15449691
TI  - [Rhabdomyosarcoma of the breast in girls].
AB  - Cases of rhabdomyosarcoma (RMS) in 14 year old girls are described. The tumor was
      very aggressive with early and widespread metastases in regional and other lymph
      nodes, soft tissues, various parts of the skeleton, bone marrow, lungs. The
      diagnosis and spread of this tumour was established on the basis of total
      examination of the girls. Clinical stage III was found in one girl, stage IV in
      two patients with RMS of the breast. Diagnoses were confirmed histologically
      (open biopsy of the tumours). Bilateral alveolar RMS of the breast (synchronic or
      metachronic) was diagnosed in all the patients. Light and electron microscopies
      were insufficient for final diagnosis, histogenesis of the tumour was established
      by means of immunohistochemistry. All the patients died within 3 months to one
      year and half after diagnosis.

PMID- 15449692
TI  - [A. I. Polunin and establishment of the department of pathologic anatomy and
      physiology at Moscow University].

PMID- 15449693
TI  - [Morphogenesis of chronic gastritis type B: update].
AB  - The article reviews current status of type B chronic gastritis morphogenesis. New
      information on Helicobacter pylori as a pathogenetic factor is presented as well
      as cell renewal of the stomach mucosa against Helicobacteriosis.

PMID- 15449694
TI  - [All-Russian conference on animal pathology (Ufa, September 17-19, 2003)].

PMID- 15449695
TI  - [Russia-Canada meeting on updated techniques of computer image processing in
      oncology].

PMID- 15449696
TI  - A test of whether attributions provide for self-enhancement or self-defense.
AB  - It is well known that people often make attributions in a way that is favorable
      to their self-concepts (see R. L. Collins, 1996, for a review). However, it is
      less clear whether the primary effect is to enhance self-esteem or to defend
      against the possible loss of self-esteem. The authors performed an experiment to
      test these possibilities against each other. In a completely between-participants
      design, participants recalled either a positive behavior or a negative behavior
      that was performed by themselves or others. They then judged the positivity or
      negativity of the behavior and made trait attributions about the actor (i.e.,
      himself, herself, or others). The results indicated that although judgments and
      trait attributions for positive behaviors were similar for the self and for
      others, judgments and trait attributions for negative behaviors were less
      negative for the self than they were for others. The authors interpreted these
      and other findings as supporting a defensive strategy rather than an enhancive
      strategy.

PMID- 15449697
TI  - Effects of objective and subjective account components on forgiving.
AB  - The authors explored the effects of the components of a harm-doer's account of
      her transgression on the victims' emotional reactions to the transgression and to
      the character traits that she attributes to the harm-doer. Participants were 480
      people whom the authors asked to imagine an incident in which they were harmed by
      the careless behavior of a friend. Subsequently, the authors offered participants
      an account of the harm-doer. In a 2 x 2 x 2 x 2 x 2 between-subjects design, the
      authors manipulated 5 account components: Admitting Fault, Admitting Damage,
      Expressing Remorse, Asking for Pardon, and Offering Compensation. The authors
      measured the participants' perceptions of these components. Results indicated
      that (a) the subjective perception of account components occurs schematically so
      that components are implicitly perceived without being objectively present, (b)
      objective components affect victims' reactions via subjective perceptions of
      these components, (c) personality factors (Irreconcilability, Interpersonal
      Trust, and Trait Anger) affect victims' reactions directly. Finally, certain
      configurations of account components are more effective than others.
      Specifically, asking for pardon had an effect on forgiving only when it was
      combined with an acknowledgment of the damage and a compensation offer. This
      result suggests that in this situation, the victim perceives a harm-doer's asking
      for pardon without the other components as an insincere apology.

PMID- 15449698
TI  - Perceptions of the social and personal characteristics of hypermuscular women and
      of the men who love them.
AB  - A predominately European American sample of middle class college students rated
      hypermuscular female bodybuilders and the men who were romantically involved with
      them on measures of perceived gender traits, personality traits, social
      behaviors, and heterosexual behaviors. Participants perceived hypermuscular
      women, as compared to the average woman, as having more masculine and fewer
      feminine interests, less likely to be good mothers, and less intelligent,
      socially popular, and attractive. However, participants also perceived them as
      being less likely to engage in socially deviant behaviors or to be sexually
      manipulative and more likely to be extraverted, conscientious, and open to new
      experiences than the average woman. Participants perceived men who are
      romantically involved with hypermuscular women as having stronger masculine
      traits, interests, and identities than the average man. The authors found no
      relationships between the perceiver's gender type and his or her perceptions of
      hypermuscular women or the men who were romantically involved with them.

PMID- 15449699
TI  - Work environment structure and psychological ownership: the mediating effects of
      control.
AB  - Current theorists on the psychology of possession highlight control as an
      important route in the development of feelings of ownership. In the present
      article, the authors hypothesized that the extent to which individuals experience
      control over their job and work environment is positively associated with
      feelings of ownership for their job and the organization. The authors used
      supervisory report data on work environment structure and self-reports on
      experienced control and psychological ownership to test for the mediating effects
      of experienced control in the relationship between the work environment structure
      and psychological ownership. The authors found that experienced control mediates
      the relationship between 3 sources of work environment structure--technology,
      autonomy, and participative decision making--and psychological ownership of the
      job and (to a lesser extent) the organization. The authors proposed implications
      of the findings and directions of further research.

PMID- 15449700
TI  - Formal names versus nicknames in the context of personal ads.

PMID- 15449701
TI  - Personality and forgiveness: a Nepalese perspective.

PMID- 15449702
TI  - Cognitive busyness and the processing of evaluative information in intergroup
      contexts.

PMID- 15449703
TI  - Molecular genetics of human cervical cancer: role of papillomavirus and the
      apoptotic cascade.
AB  - Cervical cancer is rated the second most common malignant tumour globally, and is
      aetiologically linked to human papillomavirus (HPV) infection. Here the cellular
      pathology under consideration of stem/progenitor cell carcinogenesis is reviewed.
      Of the three causative molecular mechanisms of cervical cancer, two are
      associated with HPV: firstly, the effect of the viral oncogenes, E6 and E7; and
      secondly, integration of the viral DNA into chromosomal regions of tumour
      phenotype. The third process involved is the repetitive loss of heterozygosity in
      some chromosomal regions. HPV can be classified into high- and low-risk types;
      the high-risk types encode two oncoproteins, E6 and E7, which interact with
      tumour suppressor proteins. The association results in the inactivation of tumour
      suppressor proteins and the abrogation of apoptosis. Apoptosis is referred to as
      programmed cell death, whereby a cell deliberately commits suicide, and thus
      regulates cell numbers during development and maintenance of cellular
      homeostasis. This review attempts to elucidate the role of apoptotic genes, and
      considers external factors that interact with HPV in the development and
      progression of cervical cancer. Therefore, an in-depth understanding of the
      apoptotic genes that control molecular mechanisms in cervical cancer are of
      critical importance. Useful targets for therapeutic strategies would be those
      that alter apoptotic pathways in a manner where the escape of HPV from
      surveillance by the host immune system is prevented. Such an approach directed at
      the apoptotic genes maybe useful in the treatment of cervical cancer.

PMID- 15449704
TI  - Regulatory role of membrane-bound peptidases in the progression of gynecologic
      malignancies.
AB  - Membrane-bound peptidases play a key role in the control of growth,
      differentiation, and signal transduction of many cellular systems by degrading
      bioactive peptides. Thus, abnormal changes in their expression pattern and
      catalytic function result in altered peptide activation, which contributes to
      neoplastic transformation or progression. In this review, we describe our recent
      findings along with work from other groups on the expression and biological
      functions of membrane-bound peptidases in cancer, focusing on the regulatory
      roles of three peptidases, aminopeptidase A (APA), neutral endopeptidase (NEP)
      and placental leucine aminopeptidase (P-LAP), in the progression of gynecologic
      malignancies. APA, NEP and P-LAP are differentially expressed and localized in
      various gynecologic malignancies including cervical cancer, endometrial cancer,
      ovarian cancer and choriocarcinoma in a tumor-type specific pattern. The
      expression levels are up- or down-regulated depending on histological grade or
      disease progression. These peptidases play regulatory roles in tumor cell
      proliferation, invasion or angiogenesis via degradation/inactivation of target
      peptides such as angiotensin II, endothelin-1 and oxytocin, which act on cancer
      cells as stimulatory or inhibitory factors. Thus, membrane-bound peptidases may
      become not only a new diagnostic/prognostic marker, but also a novel molecular
      target for the treatment of gynecologic malignancies.

PMID- 15449705
TI  - Functional genomics identifies novel and diverse molecular targets of nutrients
      in vivo.
AB  - Genomic responses to nutrients are important determinants of physiological and
      pathological functions of living systems. Many of these responses are mediated by
      changes in mRNA concentrations that are primarily regulated by gene
      transcription. Transcriptional networks that regulate the expression and
      activities of transcription factors and structural genes in response to nutrients
      need to be defined. The tools of functional genomics and bioinformatics offer
      powerful means to address these needs. The application of global mRNA profiling
      tools to define genome-wide responses to nutrients and micronutrients with a
      primary focus on in vivo genomic responses of vital organs of laboratory mice is
      reviewed here. The studies show that major and minor nutrients affect the
      expression of mRNAs that are related to aging and inflammation, and chemically
      diverse micronutrients such as polyphenols and tocopherols may exert their
      effects through modulating the expression of functionally related genes.

PMID- 15449706
TI  - Molecular recognition in bone morphogenetic protein (BMP)/receptor interaction.
AB  - Bone morphogenetic proteins (BMPs) and other members of the TGF-beta superfamily
      are secreted signalling proteins determining the development, maintenance and
      regeneration of tissues and organs. These dimeric proteins bind, via multiple
      epitopes, two types of signalling receptor chains and numerous extracellular
      modulator proteins that stringently control their activity. Crystal structures of
      free ligands and of complexes with type I and type II receptor extracellular
      domains and with the modulator protein Noggin reveal structural epitopes that
      determine the affinity and specificity of the interactions. Modelling of a
      ternary complex BMP/(BMPR-IA(EC))2 / (ActR-II(EC))2 suggests a mechanism of
      receptor activation that does not rely on direct contacts between extracellular
      domains of the receptors. Mutational and interaction analyses indicate that the
      large hydrophobic core of the interface of BMP-2 (wrist epitope) with the type I
      receptor does not provide a hydrophobic hot spot for binding. Instead, main chain
      amide and carbonyl groups that are completely buried in the contact region
      represent major binding determinants. The affinity between ligand and receptor
      chains is probably strongly increased by two-fold interactions of the dimeric
      ligand and receptor chains that exist as homodimers in the membrane (avidity
      effects). BMP muteins with disrupted epitopes for receptor chains or modulator
      proteins provide clues for drug design and development.

PMID- 15449707
TI  - Functional GATA- and initiator-like-elements exhibit a similar arrangement in the
      promoters of Caenorhabditis elegans polyamine synthesis enzymes.
AB  - Polyamines are essential cell constituents involved in growth processes. In
      Caenorhabditis elegans the polyamine synthetic pathway consists of three enzymes,
      ornithine decarboxylase (ODC), S-adenosylmethionine decarboxylase (AdoMetDC) and
      spermidine synthase. Their gene expression pattern was determined in C. elegans
      by microinjection of green fluorescent protein (GFP) reporter gene constructs.
      All transgenic animals exhibited GFP expression in their intestinal cells. For
      the AdoMetDC promoter, fluorescence was additionally observed in dopaminergic
      neurons, while the ODC promoter also drives a male-specific GFP expression in the
      distal part of the reproductive system. The minimal promoter regions for
      intestine-specific expression of the AdoMetDC and spermidine synthase genes were
      determined by deletion mutants. Using the Seqcomp and Family Relation programs, a
      similar arrangement of putative cis-regulatory elements within these regions and
      also within the respective regions of the orthologous Caenorhabditis briggsae
      genes were found. The functional conservation of the latter was confirmed by
      heterologous transformation experiments. Moreover, the involvement of putative
      GATA- and initiator-(Inr)-like-elements in gene expression was determined by
      mutagenesis studies. RNase protection assay revealed that the Inr-like-element
      does not represent the main transcriptional start site, at least of C. elegans
      spermidine synthase. In conclusion, a similar minimal promoter architecture was
      found for C. elegans as well as C. briggsae AdoMetDC and spermidine synthase, two
      genes that participate in the same metabolic pathway.

PMID- 15449708
TI  - Fluid shear stress induces endothelial KLF2 gene expression through a defined
      promoter region.
AB  - Fluid shear stress is crucial for maintenance of a properly functioning
      endothelium. In this study we demonstrate that the KLF2 transcription factor is
      greatly induced by pulsatile shear stress in murine microvascular endothelial
      cells. The promoter elements responsible for the induction were studied by
      transfection with luciferase-reporter plasmids including the 5' flanking region
      of the murine KLF2 gene. Deletion analysis reveals that the responses are
      regulated by a region from -157 to -95 bp from the start site of transcription.
      Furthermore, shear stress induces specific nuclear binding within this region.
      These results define a novel shear stress response region that is highly
      conserved between mouse and human homologs.

PMID- 15449709
TI  - Recombinant expression, purification and cross-reactivity of chenopod profilin:
      rChe a 2 as a good marker for profilin sensitization.
AB  - Chenopod pollen is one of the major sources of allergens in some locations in the
      US, southern Europe and desert countries, and pollen profilin (Che a 2) is a
      major allergen. Recombinant Che a 2 (rChe a 2) has been produced in Escherichia
      coil cells with a final yield of 25 mg/l of cell culture. The expressed protein
      was isolated and structurally characterized by means of mass spectrometry, Edman
      degradation and circular dichroism. rChe a 2 displayed a molecular mass of 13 959
      Da, which agrees with that of the amino acid sequence. The N-terminal amino acid
      sequence indicated the correct processing of the recombinant product. The
      immunological analysis of rChe a 2 showed IgG- and IgE-binding capabilities
      equivalent to those of its natural counterpart, Che a 2, isolated from the
      pollen. Inhibition experiments showed high cross-reactivity degrees with
      different allergenic sources. Inhibition degrees of >95% and >80% were obtained
      for chenopod profilin and, respectively, latex and pollen extracts, whereas 10
      95% of inhibition was observed for different plant-derived foods. Due to its
      close relation to other allergenic profilins from pollens, plant-derived foods
      and latex, rChe a 2 could be a useful tool in clinical trials to detect profilin
      allergic patients and perhaps, depending on its clinical relevance, in specific
      immunotherapy of these hypersensitive individuals.

PMID- 15449710
TI  - Cellular prion protein acquires resistance to proteolytic degradation following
      copper ion binding.
AB  - The conversion of cellular prion protein (PrP(C)) into its pathological isoform
      (PrP(Sc)) conveys an increase in hydrophobicity and induces a partial resistance
      to proteinase K (PK). Interestingly, co-incubation with high copper ion
      concentrations also modifies the solubility of PrP(c) and induces a partial PK
      resistance which was reminiscent of PrP(Sc). However, concerns were raised
      whether this effect was not due to a copper-induced inhibition of the PK itself.
      We have therefore analyzed the kinetics of the formation of PK-resistant PrP(C)
      and excluded possible interference effects by removing unbound copper ions prior
      to the addition of PK by methanol precipitation or immobilization of PrP(C)
      followed by washing steps. We found that preincubation of PrPc with copper ions
      at concentrations as low as 50 microM indeed rendered these proteins completely
      PK resistant, while control substrates were proteolyzed. No other divalent
      cations induced a similar effect. However, in addition to this specific
      stabilizing effect on PrP(C), higher copper ion concentrations in solution (>200
      microM) directly blocked the enzymatic activity of PK, possibly by replacing the
      Ca2+ ions in the active center of the enzyme. Therefore, as a result of this
      inhibition the proteolytic degradation of PrP(C) as well as PrP(Sc) molecules was
      suppressed.

PMID- 15449711
TI  - Distinctive functional features in prokaryotic and eukaryotic Cu,Zn superoxide
      dismutases.
AB  - Bacterial and eukaryotic Cu,Zn superoxide dismutases show remarkable differences
      in the active site region and in their quaternary structure organization. We
      report here a functional comparison between four Cu,Zn superoxide dismutases from
      Gram-negative bacteria and the eukaryotic bovine enzyme. Our data indicate that
      bacterial dimeric variants are characterized by catalytic rates higher than that
      of the bovine enzyme, probably due to the solvent accessibility of their active
      site. Prokaryotic Cu,Zn superoxide dismutases also show higher resistance to
      hydrogen peroxide inactivation and lower HCO3- -dependent peroxidative activity.
      Moreover, unlike the eukaryotic enzyme, all bacterial variants are susceptible to
      inactivation by chelating agents and show variable sensitivity to proteolytic
      attack, with the E. coli monomeric enzyme showing higher rates of inactivation by
      EDTA and proteinase K. We suggest that differences between individual bacterial
      variants could be due to the influence of modifications at the dimer interface on
      the enzyme conformational flexibility.

PMID- 15449712
TI  - Tumour-expressed CD43 (sialophorin) mediates tumourmesothelial cell adhesion.
AB  - Mesothelial cell intercellular adhesion molecule-1 (ICAM-1) has recently been
      shown to play a role in tumour cell adherence to the peritoneum. However, solid
      tumours poorly express its most ubiquitous ligand, beta2 integrin. The aim of
      this study was to investigate the role of the beta2 integrin subunit and CD43, a
      known ligand for ICAM-1, in the development of peritoneal metastases. beta2
      Integrin subunit and CD43 expression was assessed on a number of tumour cell
      lines. Adhesion of SW1222 and PSN-1 cells to human peritoneal mesothelial cells
      was investigated using a fluorometric assay incorporating an inhibitory antibody
      to beta2 integrin and CD43. beta2 Integrin expression was not inducible on these
      tumour cell lines, but Western blotting demonstrated CD43 expression in all the
      cancer cell lines examined and cell surface expression was confirmed by flow
      cytometry. The anti-CD43 antibody significantly reduced adhesion of PSN-1 and
      SW1222 cells to HPMC, however beta2 integrin inhibition did not reduce tumour
      cell adhesion. CD43 is expressed by a variety of carcinoma cell lines, and plays
      a role in tumour cell-peritoneal adhesion probably via interactions with its
      putative ligand ICAM-1.

PMID- 15449713
TI  - [Recent studies on centromere].

PMID- 15449714
TI  - [Molecular basis of kinetochore structure and kinetochore-spindle interaction].

PMID- 15449715
TI  - [Heterochromatin and centromere: heterochromatin meets RNAi].

PMID- 15449716
TI  - [Spindle checkpoint: cell cycle regulation by a signal emitted from
      kinetochores].

PMID- 15449717
TI  - [Modifications of centromeric cohesin for meiosis specific chromosome
      segregation].

PMID- 15449718
TI  - [Mammalian centromere and artificial chromosome].

PMID- 15449719
TI  - [A centromere like site on the E. coli chromosome].

PMID- 15449720
TI  - [The pharmacogenomics of drug transporters: functional analysis approaches].

PMID- 15449721
TI  - [The sophisticated proton pump, V-type ATPase].

PMID- 15449722
TI  - [Necdin/MAGE family: signaling proteins for cell proliferation, differentiation,
      and death].

PMID- 15449723
TI  - New aromatic esters of progesterone as antiandrogens.
AB  - The in vivo and in vitro antiandrogenic activity of four new progesterone
      derivatives: 4-bromo-17alpha-(p-fluorobenzoyloxy)-4-pregnene-3,20-dione 1,4-bromo
      17alpha-(pchlorobenzoyloxy)-4-pregnene-3,20-dione 2, 4-bromo-17alpha-(p
      bromobenzoyloxy)-4-pregnene-3,20-dione 3 and 4-bromo-17alpha-(p-toluoyloxy)-4
      pregnene-3, 20-dione 4 was determined. These compounds were evaluated as
      antiandrogens on gonadectomized hamster prostate and reduced the weight of the
      prostate glands in gonadectomized hamsters treated with testosterone 5 (T) or
      dihydrotestosterone 6 (DHT) in a similar manner to that of commercially available
      finasteride, thus indicating a potent in vivo effect. The in vitro studies showed
      that steroids 1-4 have a weak inhibitory activity on 5alpha-reductase with IC50
      values of: 280 (1), 2.6 (2), 1.6 (3) and 114 microM (4). The presence of Cl and
      Br atoms in the C-17 benzoyloxy group tends to increase the inhibitory potency of
      the compounds. The binding efficiency of the synthesized steroids 1-4 to the
      androgen receptor of the prostate gland is also evaluated. All compounds form a
      complex with the receptor and this explains the weight reduction of the seminal
      vesicles in the animals treated with DHT plus steroids 1-4.

PMID- 15449724
TI  - Synthesis of alpha-mannosylated phenolics as alpha-glucosidase inhibitors.
AB  - BF3OEt2-catalysed glycosidation of phenolic compounds 3 and 6 with the
      mannofuranosyl glycosyl donor 2 separately gave the corresponding alpha
      mannofuranosyl derivatives 4 and 7 in good yield, and the latter on selective
      deacetonation (hydrolysis) with 2% aqueous HCl afforded 5 and 8 respectively.
      Compounds 4 and 7 inhibited rat intestinal alpha-glucosidase more effectively
      than a standard drug acarbose.

PMID- 15449725
TI  - Interaction of human butyrylcholinesterase variants with bambuterol and
      terbutaline.
AB  - Bambuterol, a dimethylcarbamate, carbamoylates butyrylcholinesterase (BChE; EC
      3.1.1.8). The carbamoylated enzyme is not very stable and the final product of
      the two-step hydrolysis is a bronchodilator drug, terbutaline (1-(3,5
      dihydroxyphenyl)-2-t-butylamino-ethanol sulphate). Both bambuterol and
      terbutaline inhibit BChE, but their affinities differ in human serum BChE
      variants (U, A, F, K and S) due to their positive charge. Bambuterol inhibition
      rate constants for the homozygous usual (UU), Kalow (KK), fluoride-resistant (FF)
      or atypical (AA) variant ranged from 4.4 to 0.085min (-1)microM(-1). Terbutaline
      showed competitive reversible inhibition for all BChE variants. The dissociation
      constants for UU, FF and AA homozygotes were 0.18, 0.31 and 3.3 mM, respectively.
      The inhibition rate or dissociation constants for heterozygotes were distributed
      between the respective constants for the corresponding homozygotes. A 50-fold
      difference in inhibition between the UU and AA enzyme might affect terbutaline
      release in humans. The affinity of all studied BChE variants for terbutaline was
      low, which suggests that terbutaline originating from bambuterol hydrolysis
      should not affect the hydrolysis of bambuterol by BChE.

PMID- 15449726
TI  - Synthesis and evaluation of benzoxazolinonic imidazoles and derivatives as non
      steroidal aromatase inhibitors.
AB  - New compounds were tested in vitro on aromatase activity in human placental and
      equine testicular microsomes. Equine aromatase, very well characterized
      biochemically, is used as a comparative model to understand the mechanism of
      aromatase inhibition. Among 15 molecules screened, 5 of them (11-15) strongly
      inhibit human and equine aromatases with IC50 values ranging from 13-85nM and
      from 23-103nM respectively. These results were corroborated by Ki/Km values.
      Moreover, spectral studies showed a type II spectrum with both enzymes, which is
      characteristic of an interaction between the nitrogen atom of the molecule and
      the heme of the cytochrome P450. Compound 12, which has the lowest IC50 and Ki/Km
      ratio, inactivates aromatase in a dose and time-dependent manner. This might be
      very important for the treatment of estrogen-dependent diseases such as breast
      cancer. Finally, MTT assays on E293 cells revealed that the molecules were not
      cytotoxic.

PMID- 15449727
TI  - Synthesis and antioxidant properties of novel benzimidazole derivatives.
AB  - Some novel benzimidazole derivatives carrying thiosemicarbazide and triazole
      moieties at the N1 position were synthesized and their in vitro effects on rat
      liver microsomal NADPH-dependent lipid peroxidation (LP) levels determined by
      measuring the formation of 2-thiobarbituric acid reactive substance. The free
      radical scavenging properties of the compounds were also examined in vitro by
      determining the capacity to scavenge superoxide anion formation and the
      interaction with the stable free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH).
      The compounds showed a significant effect in the above tests except to scavenge
      superoxide anion formation.

PMID- 15449728
TI  - Design and synthesis of indole and tetrahydroisoquinoline hydantoin derivatives
      as human chymase inhibitors.
AB  - The synthesis of new potential inhibitors of human chymase is described.
      Treatment of dihydroimidazo[1,5-a]indole and [1,5-b]isoquinoline-dione with
      thioaryl followed by oxidation gave the N-arylsulfonylmethyl of polycyclic
      hydantoin derivatives 3, 5 and 6.

PMID- 15449729
TI  - CYP 17 and CYP 19 inhibitors. Evaluation of fluorine effects on the inhibiting
      activity of regioselectively fluorinated 1-(Naphthalen-2-ylmethyl)imidazoles.
AB  - Regioselectively fluorinated 1-(naphth-2-ylmethyl)imidazoles 1a-h have been
      synthesized starting from the corresponding (naphth-2-yl)methanols (2). 2a-d have
      been obtained by LiAlH4-promoted reduction of fluorinated 1-methyl-2
      naphthaldehydes. The latter were easily prepared in fairly good overall yields by
      ceric ammonium nitrate (CAN)-promoted oxidative addition of the suitable 3
      (fluoroaryl)-1-trimethylsilyloxy-1-butenes to ethyl vinyl ether in methanol
      followed by cyclization of the resulting acetals in strongly acidic medium in the
      presence of DDQ. 2e-h were prepared by LiAlH4-promoted reduction of the
      corresponding fluorinated methyl 2-naphthoates. The latter were more profitably
      obtained by reacting the suitable benzyl bromide with the sodium salt of dimethyl
      2-(2,2-dimethoxyethyl)malonate in DMF followed by demethoxycarbonylation and acid
      catalysed cyclization of the resulting acetals. Compared with the nonfluorinated
      parent compounds 1i-1, fluorinated 1-(naphth-2-yl)methylimidazoles 1a-h turned
      out to be potent inhibitors of CYP17 and CYP19 enzymes. The most active inhibitor
      of CYP17 is 1c, whereas CYP19 is strongly inhibited by 1b, 1e, and 1g.
      Interestingly, 1g is a potent dual inhibitor also being very active towards
      CYP19.

PMID- 15449730
TI  - Inhibition of beta-amylase activity by calcium, magnesium and zinc ions
      determined by spectrophotometry and isothermal titration calorimetry.
AB  - The inhibition effect of metal ions on beta amylase activity was studied. The
      inhibitor-binding constant (Ki) was determined by spectrophotometric and
      isothermal titration calorimetric (ITC) methods. The binding of calcium,
      magnesium and zinc ion as inhibitors at the active site of barley beta amylase
      was studied at pH = 4.8 (sodium acetate 16 mM) and T = 300K. The Ki and enthalpy
      of binding for calcium (13.4, 13.1 mM and -14.3 kJ/mol), magnesium (18.6, 17.8mM
      and -17.7 kJ/mol) and zinc (17.5, 17.7 mM and -20.0 kJ/mol) were found by
      spectrophotometric and ITC methods respectively.

PMID- 15449731
TI  - Antibacterial and antifugal mono- and di-substituted symmetrical and
      unsymmetrical triazine-derived Schiff-bases and their transition metal complexes.
AB  - A new series of antibacterial and antifungal triazine-derived mono- and di
      substituted (symmetrical and unsymmetrical) Schiff-bases and their cobalt(II),
      copper(II), nickel(II) and zinc(II) metal complexes have been synthesized and
      characterized by their elemental analyses, molar conductances, magnetic moments
      and IR and electronic spectral measurements. IR spectra indicated the ligands to
      act as tridentate towards divalent metal ions via a trazine-N, the azomethine-N
      and, indole-NH and deprotonated-O of salicylaldehyde. The magnetic moments and
      electronic spectral data suggest octahedral geometry for the Co(II), Ni(II) and
      Zn(II)complexes and square-pyramid for Cu(II) complexes. NMR spectral data of the
      ligands and their diamagnetic zinc(II) complexes well-define their proposed
      structures/geometries. Elemental analyses data of the ligands and metal complexes
      agree with their proposed structures/geometries. The synthesized ligands, along
      with their metal complexes were screened for their antibacterial activity against
      Escherichia coli, Bacillus subtillis, Shigella flexneri, Staphylococcus aureus,
      Pseudomonas aeruginosa and Salmonella typhi and for antifungal activity against
      Trichophyton longifusus, Candida albicans, Aspergillus flavus, Microsporum canis,
      Fusarium solani and Candida glaberata. The results of these studies show the
      metal complexes to be more antibacterial/ antifungal against two or more species
      as compared to the uncomplexed Schiff-base ligands.

PMID- 15449732
TI  - Inactivation of cytochrome-c with glucose oxidase.
AB  - A novel reaction of cytochrome-c from the horse heart with the enzyme glucose
      oxidase from Aspergillus niger (EC 1.1.3.4), in acidic media is described.
      Glucose oxidase is able to induce a rapid, profound and irreversible physico
      chemical change in cytochrome-c, under anaerobic conditions and in the presence
      of glucose. The initial rate of reaction is almost independent of the
      concentration of enzyme and glucose. The striking feature of this reaction is the
      fact that the reaction proceeds efficiently even below a concentration of 10 nM
      enzyme.

PMID- 15449733
TI  - Glutathione and cinnamic acid: natural dietary components used in preventing the
      process of browning by inhibition of Polyphenol Oxidase in apple juice.
AB  - Consumer demands for 'freshness' in processed foods has been given increasing
      attention by food processing industries by searching for minimally processed
      products. Polyphenol Oxidase (PPO) mediated browning is a major cause of
      undesirable flavors and nutritional losses in fruit juices. Here the anti
      browning efficiency of glutathione (GSH, reduced form) and cinnamic acid (CA) in
      apple juice is evaluated. It was observed that the rate of the browning reaction
      could be efficiently delayed using GSH and CA, which act as inhibitors of PPO.
      Kinetic studies confirm that GSH and CA are non-competitive and competitive
      inhibitors of PPO respectively.

PMID- 15449734
TI  - The effect of carbonic anhydrase inhibition on leptin secretion by rat adipose
      tissue.
AB  - It is well known that the role of leptin in the body is to regulate food intake
      and energy expenditure but the process of leptin secretion by adipose tissue and
      the components involved in this process are still obscure. Carbonic anhydrase III
      (CA III) is the most abundant protein of the rat adipose tissue and its amount
      decreases with obesity. The effect of the inhibition of CA III on leptin
      secretion by rat epididymal adipose tissue was examined. Dorzolamide, a CA
      inhibitor, caused a decrease in dexamethasone and insulin-induced leptin
      secretion suggesting a possible role for CA III in the mechanism of leptin
      secretion.

PMID- 15449735
TI  - Antineoplastic and antibacterial activity of some mononuclear Ru(II) complexes.
AB  - These ligands (L) show a bidentate behavior, forming octahedral ruthenium
      complexes. The title complexes were subjected to in-vivo anticancer activity
      tests against a transplantable murine tumor cell line, Ehrlich's Ascitic
      Carcinoma (EAC) and in-vitro antibacterial activity against several Gram positive
      and Gram negative bacterial strains. [Ru(bpy)2(ihqs)]Cl2 and [Ru(bpy)2 (hc)]Cl2
      (where bpy = 2,2'-bipyridine, ihqs = 7-iodo-8hydroxy quinoline-5-sulphonic acid
      and hc = 3-hydroxy coumarin) showed promising antitumor activity. Treatment with
      these complexes prolonged the life span of EAC bearing mice as well as decreased
      their tumor volume and viable ascitic cell count. All the tested complexes
      exhibited mild to moderate antibacterial activity.

PMID- 15449736
TI  - Effects of melatonin on carbonic anhydrase from human erythrocytes in vitro and
      from rat erythrocytes in vivo.
AB  - The in vitro effects of melatonin (N-acetyl-5-methoxy-tryptamine) on human
      carbonic anhydrase isozymes (HCA-I and HCA-II) from human erythrocytes and in
      vivo effects on rat erythrocytes carbonic anhydrase (CA) were determined. Human
      erythrocyte carbonic anhydrase isozymes were purified by haemolysate preparation
      and Sepharose-4B-L tyrosine-sulfanilamide affinity gel chromatography. The HCA-I
      enzyme, having a specific activity of 7337.5 EU/mg protein, was purified 843-fold
      with a yield of 60% and the HCA-II enzyme, having a specific activity of
      17067EU/mg protein, was purified 1962-fold with a yield of 22.7%. For in vitro
      experiments, the enzyme activity was minimal at 2 x 10(-4) M melatonin
      concentration and increased above this concentration. Ten mgkg(-1) melatonin was
      administered intraperitoneally and showed a stimulatory effect on the enzyme.
      Time-dependent in vivo studies were conducted for melatonin in Sprague-Dawley
      type rats. It was found that CA activity in the rat erythrocytes was decreased by
      the melatonin after 1 and 3 hours to 2500 +/- 500.0 and 1875 +/- 239.4
      respectively which were statistically significant (p < 0.05) differences to the
      control (2660 +/- 235.8). However, CA activity was restored to its normal level
      after 6h (2666 +/- 235.7) (p > 0.05) probably due to metabolism of the melatonin.
      The findings indicate that melatonin may be pharmacologically useful in some
      diseases.

PMID- 15449737
TI  - Welcome message from the President of the 13th World Congress of
      Anaesthesiologits.

PMID- 15449738
TI  - Dr. Adib Abou Haidar: the first to take up the anesthesia residency training for
      physicians at the American University Hospital in Beirut, Lebanon.

PMID- 15449739
TI  - Reminiscences of a physician-anesthesiologist in Lebanon.

PMID- 15449740
TI  - Desflurane vs. sevoflurane--a review.

PMID- 15449741
TI  - Effects of sevoflurane, propofol and position changes on respiratory mechanics.
AB  - This study was designed to investigate the effects of propofol, sevoflurane and
      position changes on respiratory mechanics. Forty patients scheduled for thyroid
      surgery were divided randomly into two groups; those receiving sevoflurane (group
      S) (n=20), and those receiving TIVA propofol (group P) (n=22). Dynamic compliance
      (Cdyn), peak inspiratory pressure (PIP), and respiratory resistance (Rr) values
      were recorded with a VenTrak respiratory monitor (Novometrix Inc. USA) at three
      time instances. The first measurement was done immediately after the beginning of
      ventilation and before the inhalation agent was initiated (Induction). Second
      measurement was done after 5 minutes of thyroid position (Thyroid) (ventilation
      with 1 MAC sevoflurane concentration or propofol infusion at the rate of 6
      mg/kg/h). The third measurement was performed 5 minutes after end of surgery in
      the supine position (Supine) Blood gases were measured at the three time
      instances. Respiratory mechanics did not change in the P group (51 +/- 13, 46 +/-
      11, 48 +/- 10 mL/cmH2O) at Induction, Thyroid and Supine positions). In the S
      group, dynamic compliance measurements showed changes statistically significant
      in the supine position (52 +/- 6 mL/cmH2O)) when compared to Induction (47 +/- 9
      mL/cmH2O) and Thyroid position (47 +/- 6 mL/cmH2O) measurements (p<0.05). When
      the groups were compared with each other, there was no significant difference
      whatsoever at all periods (p>0.05). His concluded that sevoflurane, propofol and
      position changes exhibit similar effects on respiratory mechanics and blood gases
      at described dose and concentration.

PMID- 15449742
TI  - Propofol and sevoflurane during epidural/general anesthesia: comparison of early
      recovery characteristics and pain relief.
AB  - We investigated the early recovery characteristics and pain relief of adult
      patients during combined anesthesia with (epidural and general), either with
      propofol or sevoflurane for maintenance in major abdominal surgery. Twenty-two
      patients (ASA I-III) were enrolled in this randomized, prospective study. After
      fluid preloading, 10 ml of bupivacaine 0.5% + 5 ml of prilocaine 0.5% + 1 ml of
      fentanyl 50 microg mL(-1) were administered via an epidural catheter. General
      anesthesia was induced with fentanyl and propofol after T6 sensorial blockade.
      Propofol group (n = 11) received propofol (2-5 mg kg(-1) h(-1)), sevoflurane
      group (n = 11) received sevoflurane (1-2%) for maintenance. Anesthesia was
      supplemented with N2O in O2 and intravenous fentanyl. Continuous epidural
      infusion of 0.125% bupivacaine + 1 microg fentanyl (5-7 mL h(-1)) was started
      forty-five min after the epidural bolus dose and 5 ml of it was given at the
      start of the wound closure. All anesthetics were discontinued except epidural
      infusion during the last suture. After emergence time was determined, the
      patients were transferred to the PACU. They were observed for orientation times
      of person and place. The pain scores (verbal analogue scale, 0-10) were assessed
      with 30 min intervals. When the patient's pain score was >3, rescue analgesic
      protocol (diclofenac Na 75 mg im followed by meperidine HCI approximately 0.25 mg
      kg(-1) iv at the latter period) was applied. In the case of inadequate pain
      relief during the latter assessment periods, meperidine HCI approximately 0.25 mg
      kg(-1) was administered. Mann-Whitney U test and Fisher's exact test were used
      for the statistical analysis. A value of p<0.05 was considered significant.
      Between the groups no statistical differences were observed in the emergence time
      (5 vs. 6 min, median) and in the orientation time to person (6 vs. 10 min).
      Recovery of orientation to place was found faster in propofol group (7 vs. 12
      min, p = 0.041). Pain scores of the patients between the groups were not
      statistically different at 0, 30, 60, 90, 120 min postoperatively (3, 2, 3, 2, 2,
      and 2, 4, 4, 3, 3, respectively). Rescue analgesic protocol and additional
      meperidine HCI were applied to 63.6% and 45.4% of patients in the propofol group,
      54.5% and 36.3% of patients in the sevoflurane group, respectively. There weren't
      any statistical differences in regard to these, either. Except orientation time
      to place, the times of emergence and orientation to person, the pain scores and
      the analgesic requirements of the patients in both groups were similar. Propofol
      or sevoflurane did not offer any advantages for postoperative pain relief on
      behalf of either one when combined with epidural anesthesia.

PMID- 15449743
TI  - Induced preconditioning of cardiac performance in coronary bypass surgery-
      sevoflurane vs propofol.
AB  - Twenty ASA III and IV adult patients scheduled for elective coronary artery
      surgery were included in the study. Anesthesia was induced and maintained with
      either sevoflurane (sevoflurane group; n = 10) or propofol (propofol group; n =
      10). All preoperative cardiac medications were continued until the morning of
      surgery. There were significant decreases in mean arterial blood pressure,
      cardiac index and ejection fraction after CPB in propofol group compared with
      sevoflurane. Further, the plasma creatine kinase myocardial isoenzyme
      concentrations were significantly higher in propofol group but did not approach
      the critical values needed for diagnosis of myocardial infarction. CONCLUSION: It
      is concluded that, sevoflurane appears to be associated with better hemodynamic
      stability before and after CPB than propofol. This could be attributed to
      cardioprotective effect of sevoflurane during ischemia and reperfusion.

PMID- 15449744
TI  - Management strategies for the difficult pediatric airway.

PMID- 15449745
TI  - Premedications and peribulbar analgesia--a prospective audit.
AB  - PURPOSE: After peribulbar block analgesia (PBA) instituted in the preoperative
      anesthetic room, patients are often anxious, developing increased heart rate (HR)
      and blood pressure (BP) upon their arrival to the operating room and during
      subsequent surgery. The efficacy of premedication in attenuating these stress
      responses has not been examined. A prospective audit was undertaken to examine
      the relationship between the premedication schedules most commonly prescribed at
      the King Khaled Eye Specialist Hospital and increases in HR and BP during surgery
      in response to the stress of surgery, and the requirements for intravenous (IV)
      benzodiazepine, opioid or NSAID medication to treat these increases, or any
      complaint of pain or positional discomfort on the operating table, respectively.
      METHODS: The preoperative and intraoperative anesthesia course of 1,064 patients
      > or = 50 years of age who underwent ocular surgery under PBA was prospectively
      examined. The following data were recorded: (i) patient characteristics, state of
      health or disease, medications and premedications; (ii) heart rate (HR), systolic
      arterial pressure (SAP), and diastolic arterial pressure (DAP) at 0600 hrs before
      surgery (baseline), on admission to the operating room, maximum and minimum
      values of HR, SAP and DAP recorded at the start of, and during, surgery; and
      (iii) all instances of benzodiazepine, opioid or NSAID drug administration during
      surgery, according to standard protocols. RESULTS: Five premedication schedules
      were identified: Group 1 hydroxyzine po alone (n = 302); Group 2 hydroxyzine,
      paracetamol with codeine (Revacod), diclofenac po (N = 173); Group 3 hydroxyzine,
      diclofenac, ranitidine po (N = 94); Group 4 hydroxyzine, cimetidine or ranitidine
      po, morphine or pethidine IM (N = 340); and Group 5 lorazepam (nocte),
      hydroxyzine, diclofenac, ranitidinepo, morphine or meperidine IM (N = 155). The
      five groups of patients were comparable for age, sex, weight and health. Healthy,
      diseased (with concurrent hypertension, diabetes, ischemic heart disease) and all
      patients in each premedication group had similar baseline HR, SAP and DAP. In the
      operating room, the maximum and minimum mean HR in each group was similar, except
      that more patients in Group 1 developed SAP exceeding 160 mmHg and DAP exceeding
      90 mmHg than in Group 5 (p<0.002 and <0.0005, respectively). The requirements for
      medication at the commencement of, and during, surgery in the five groups to
      treat increases in HR/BP, eye pain and positional discomfort on the operating
      table were similar. CONCLUSION: Each of the five premedication schedules
      described appear to confer similar effects on cardiovascular changes in
      anticipation of, and during, surgery, except that those given the lightest
      premedication, Group 1, showed greater increases in BP at the start of surgery
      than did those given the heaviest premedication, Group 5. The requirements in the
      operating room for IV medication were similar in the five premedication groups,
      and no greater benefit was discernible for any one of the five premedication
      schedules on the objective features assessed. These data suggest that simple oral
      premedication of hydroxyzine, with or without an H2 receptor antagonist and
      NSAID, may suffice as premedication in middle-aged to elderly patients undergoing
      anterior segment surgery.

PMID- 15449746
TI  - Hypokalemic paralysis mimicking Guillain-Barre syndrome and causing acute
      respiratory failure.
AB  - A 33-year-old female patient admitted to the ICU with ascending muscle weakness
      leading to acute hypercapneic respiratory failure. She gave a 10-day history of
      severe diarrhea and vomiting. Laboratory work up revealed severe hypokalemia,
      mixed metabolic and respiratory acidosis, and renal impairment. Continuous
      potassium replacement produced rapid and complete recovery from quadriplegia and
      respiratory failure without requirement for mechanical ventilation.

PMID- 15449747
TI  - Post operative analgesia with continuous epidural infusion.
AB  - Forty eight ASA I or II patients of either sex between 20-70 years undergoing
      major upper abdominal surgery were grouped into sixteen each, on complaint of
      pain. They received an epidural bolus dose, followed by infusion of the assigned
      drug at 4ml per hour through BARD PCA I pump. Pain assessment, for the first four
      hours, was hourly, and subsequently at l0th, 16th, 22nd, 28th, 36th and 40th hour
      by VAS and VRS. The groups matched for demographic distribution. All groups had
      lower mean pain scores at first hour by VAS and VRS. In Group II and Group III,
      the difference was significant (<0.05) at the 2nd (VAS) and 4th (VRS) hours. From
      16th (VAS) and 22nd (VRS) hours, the mean pain score was less and significant
      (<0.05) in Group III. In all groups sedation ranged from 0-1. There was
      hypotension in Group I (2/16).urinary retention in Group II (8/9 not
      catheterised); unilateral sensory impairment and motor weakness in Group I (3/16)
      and Group III (1/16). This study showed that continuous infusion of low dose
      morphine with bupivacaine provides better quality post operative analgesia with
      fewer side effects than bupivacaine or morphine alone.

PMID- 15449748
TI  - PCA after subarachnoid block for cesarean section.
AB  - We studied the pain control, narcotic side effects, and PCA utilization with
      intravenous PCA morphine during 24 hours post cesarean section period. Fifty-two
      consecutive women were included in the study. Each received subarachnoid block
      with hyperbaric bupivacain with addition of fentanyl. After surgery, the patient
      received diclofenac suppository and IV-PCA commenced in the recovery room.
      Severity of pain and sedation was assessed hourly, and maximum pain and sedation
      scores for each 6-hour period were recorded. Two-third of the patients felt mild
      to moderate pain during transition from spinal analgesia to IV-PCA. Pain severity
      steadily improved during four 6-hour periods (p-value <0.001). Highest mean
      sedation score was noticed during the third six-hour postoperative period. Mean
      morphine consumption was 50 mg. The ratio between number of time PCA activated
      and dose received and pain score helped in managing the postoperative pain.
      Morphine IV-PCA, adequately replaces post cesarean section spinal (bupivacain
      fentanyl) analgesia with fewer side effects.

PMID- 15449749
TI  - Bronchospastic disease and emergency surgery.

PMID- 15449750
TI  - Management of pre-eclampsia/eclampsia.
AB  - Preclampsia/eclampsia affects only a small proportion of all pregnancies, yet it
      is associated with significant morbidity and mortality for mother and baby, with
      post partum resolution. The disorder is triggered by a placental pathology
      followed by a wide spectrum of maternal systemic response. However, there remains
      controversy in practically every aspect of the condition. A full understanding of
      the condition, its variable presentation allows the consulting anesthetist to
      optimize a plan for anesthetic management.

PMID- 15449751
TI  - Discomfort, awareness and recall in the intensive care-still a problem?
AB  - INTRODUCTION: During surgery, anesthetists take extra care to prevent patient
      awareness done mainly under general anesthesia either by using inhalational or
      intravenous medications. However, patients in the ICU mainly those on ventilatory
      support with intubation and sedation, pass through lot of psychological stress
      and frustration. Most of the times this stress phenomenon is not documented in
      the general intensive care. This is the first report in our general ICU. AIM OF
      THIS STUDY: Assessment of this stress phenomenon in order to avoid it in future,
      and to elicit proper consensus regarding its existence and offer methods of re
      solution. METHODS: Seventy patients aged (20-60) years were interviewed one day
      after discharge from the ICU, about their memory of events during their stay.
      Patients with head injury, CNS infection and those who were disoriented at the
      time of interview were excluded from the study. The remaining 55 patients were
      oriented as to place and time. Intravenous morphine was used for analgesia as
      required, while sedation was achieved using midazolam and morphine infusions in
      appropriate doses as decided by the attending doctors and nurses, to achieve
      appropriate Ramsay sedation score. Questions asked were patient's memory of
      events and their distressing experiences regarding pain, anxiety, dreams, fear,
      noises, and other discomforts. The same questions were repeated 5 days later.
      RESULTS: The sample of patients were representative of our regular ICU admissions
      in their age group, APACHE II score and duration of stay. The most distressing
      experiences recalled were: Anxiety (68%), discomfort from endotracheal tube
      (60%), fear (54%), pain (52%), discomfort from N/G tube (48%), difficulty in
      communicating (33%), dreams and hallucinations (31%), discomfort from
      physiotherapy (24%), noise (15%), insomnia (13%), thirst (10%), muscle paralysis
      (100%), some of these like anxiety, fear, dreams, hallucinations and insomnia had
      continued since discharge in 6% of patients. None of the studied experiences
      correlated with age, sex or with the APACHE II score. On interviewing the patient
      5 days later, there were no significant change in their responses. CONCLUSION:
      Our sedation and analgesia in the ICU is not enough to prevent unpleasant
      experiences, mainly those related to patient awareness. More work is still needed
      i.e. using sedation measuring systems, to improve our sedation and analgesia in
      the ICU.

PMID- 15449752
TI  - Hydroxyethylstarch 6% preload does not prevent the hypotension following
      induction with propofol and fentanyl.
AB  - PURPOSE: To study the effects of volume preload with hydroxyethylstarch 6% (HES)
      on the changes in arterial blood pressure and heart rate following
      propofol/fentanyl induction of anesthesia. METHODS: Seventy five patients,
      divided into three groups, scheduled for orthopedic surgery were allocated
      randomly to receive either no preload or 500 ml, or 1000 ml of 6% HES
      respectively over 20 minutes period prior to anesthetic induction. Anesthesia was
      induced with fentanyl 1.5 microg.kg(-1) and propofol 2.5 mg.kg(-1).
      Cardiovascular parameters were monitored for 5 minutes following induction.
      RESULTS: Systolic blood pressure (SBP) decreased significantly (P<0.001) in all
      groups after anesthetic induction. Blood pressure recorded at 5 minutes was 76%
      of the baseline values in the control group and in the HES 500 group and was 78%
      in the HES 1000 group. Changes in the diastolic blood pressure (DBP) and mean
      blood pressure (MBP) were also similar in the three groups. There was no
      significant difference between the three groups in the HR decline too.
      CONCLUSION: Administration of 6% HES as a preload did not attenuate the decrease
      in blood pressure following induction of anesthesia with propofol and fentanyl.

PMID- 15449753
TI  - Comparison of serum cortisol level in open heart surgery--morphine versus
      sufentanil.
AB  - BACKGROUND AND AIMS: In open-heart surgery, cardiopulmonary bypass (CPB) can
      cause a rise in the level of stress hormones such as cortisol. Reducing this
      hormonal response is beneficial in the recovery period. Anesthetic agents and
      methods used in such operations have different effects on this response. In the
      present study two agents (morphine and sufentanil) routinely used for the cardiac
      surgery in Nemazi Hospital were compared regarding their effect on the serum
      cortisol levels. MATERIALS AND METHODS: Thirty patients undergoing coronary
      artery bypass grafting (CABG) in Nemazi Hospital were selected and divided into
      two groups. Group 1 (16 patients received morphine in a dose of 1 mg/kg) and
      Group 2 (14 patients received sufentanil in a dose of 5 microg/kg). Serum
      cortisol levels were measured before induction of anesthesia, after tracheal
      intubation, after initiation of CPB and twelve hours after the termination of
      operation. RESULTS: Morphine and sufentanil both lowered the serum cortisol level
      during the operation. However, twelve hours after the operation, cortisol levels
      in both groups were higher than those taken in the previous set times.
      CONCLUSION: Neither morphine nor sufentanil in the mentioned doses could reduce
      the endocrine response in the postoperative period, and thus have no preference,
      in cardiac surgery.

PMID- 15449754
TI  - Insulin adsorbance to polyvinylchloride (PVC) surfaces of fluid container and
      infusion-set.
AB  - INTRODUCTION: In total parenteral nutrition (TPN) solution, adsorbance of insulin
      to polyvinylchloride (PVC) surfaces of fluid containers and infusion-sets,
      decrease the amount of insulin that reaches the patients. OBJECTIVE: To clarify
      the biding sites of insulin and to propose a solution to overcome this problem.
      METHODS AND MATERIALS: To each of four 1000ml. PVC bottles of 5 percent dextrose
      solution, 300 microunit of insulin per each milliliter of dextrose solution were
      added. Each bottle was then connected to an infusion-set and the system made to
      run at an infusion rate of 100ml. per hour. One milliliter samples were then
      collected from both the PVC bottles and infusion-sets-terminal, separately,
      immediately at the starting point (time zero) and 15, 30, 45 and 60 minutes
      thereafter. The concentrations of insulin were checked using insulin kits.
      RESULTS: At the starting point (time zero) the mean of insulin concentrations
      among four PVC bottles was 213.79 microunit per each milliliter of 5 percent
      dextrose solution. No significant fluctuation was noted in the concentration of
      insulin in the PVC bottles through 60th minute period. However the concentration
      of insulin at infusion-set- terminal decreased significantly at the end of the
      same hour (p. value = 0.004). CONCLUSION: Our results demonstrate that the
      adsorbance of insulin takes place at the surfaces of infusion sets. It follows
      therefore that increase in the primary dosage of insulin added to PVC infusion
      solutions and the selection of a suitable infusion set (polyethylene) seem to be
      beneficial for overcoming this problem.

PMID- 15449755
TI  - It's what's inside the white coat that counts.

PMID- 15449756
TI  - Lessons from the PROVE-IT trial. Higher dose of potent statin better for high
      risk patients.
AB  - The Pravastatin or Atorvastatin Evaluation and Infection Therapy trial (PROVE
      IT/TIMI-22) showed that in patients with acute coronary syndromes, aggressive
      lipid-lowering using atorvastatin 80 mg/day provided greater protection against
      death or major cardiovascular events than did moderate lipid-lowering using
      pravastatin 40 mg/day. Lowering the low-density lipoprotein cholesterol level to
      approximately 62 mg/dL with atorvastatin resulted in a 16% reduction in
      cardiovascular end points.

PMID- 15449757
TI  - Cancer pain: how to measure the fifth vital sign.
AB  - Pain assessment is essential to good pain management and quality assurance. A
      pain-rating scale should be used, in combination with a thorough history and a
      general physical examination. Radiologic studies are an ancillary component
      rather than a substitute for this process. Outpatient pain diaries and hospital
      recordings of pain severity with the vital signs facilitate communication. Part
      of the goal should be to improve function and quality of life.

PMID- 15449758
TI  - Acute leukemia with a very high leukocyte count: confronting a medical emergency.
AB  - From 5% to 30% of adult patients with acute leukemias present with
      hyperleukocytosis--very high white blood cell counts (> 100,000 cells/mm3)--and
      symptoms of leukostasis. These conditions are a medical emergency that needs
      prompt recognition and initiation of therapy to prevent respiratory failure or
      intracranial hemorrhage. Patients should be referred as soon as possible for
      induction chemotherapy and leukapheresis.

PMID- 15449759
TI  - Evaluation of hyponatremia: a little physiology goes a long way.
AB  - Hyponatremia is common in hospitalized patients. By taking a careful and logical
      approach, one can promptly recognize the causative factor or factors in nearly
      all cases. Most cases of hyponatremia are due to impaired renal water excretion,
      and recognizing the cause and pathophysiologic process makes it possible to
      provide focused individualized care and avoid mistreatment.

PMID- 15449760
TI  - A 76-year-old woman with erratic anticoagulation.

PMID- 15449761
TI  - Nonalcoholic fatty liver disease and the epidemic of obesity.
AB  - Nonalcoholic fatty liver disease (NAFLD) is common in patients with the metabolic
      syndrome, and it is expected to become more common in countries where obesity,
      one of the components of the metabolic syndrome, is increasing.

PMID- 15449762
TI  - Angiotensin-receptor blockers in heart failure: evidence from the CHARM trial.
AB  - The large Candesartan in Heart Failure Assessment of Reduction in Mortality and
      Morbidity (CHARM) trial recently found that in patients with heart failure who
      were similar to those whom clinicians see in everyday practice, the angiotensin
      receptor blocker candesartan was not only an acceptable alternative to
      angiotensin-converting enzyme (ACE) inhibitors, but also was beneficial when
      added to regimens that already included ACE inhibitors and beta-blockers.
      Candesartan was beneficial in heart failure patients with or without left
      ventricular systolic dysfunction.

PMID- 15449763
TI  - And an ARB makes nine: polypharmacy in patients with heart failure.

PMID- 15449764
TI  - [Genotyping of Helicobacter pylori].

PMID- 15449765
TI  - [Chronic alcoholic and non-alcoholic steatohepatitis].

PMID- 15449766
TI  - [The nature of a relationship of nitric oxide with angiotensin-converting enzyme
      and malonic dialdehyde in patients with atherogenic stenosis of the internal
      carotid artery].
AB  - In patients with stenosis of the internal carotid artery (ICA), a relationship
      was studied between the level of nitric oxide (NO) and the activity of
      angiotensin-conversing enzyme (ACE) and malonic dialdehyde (MDA) in the blood
      serum taken from: 1) the cubital vein an hour before carotid endarterectomy; 2)
      ICA before surgery; 3) the internal jugular vein before surgery; 4) ICA 5 min
      after surgery; 5) the internal jugular vein 5 min after surgery; 6) the cubital
      vein an hour following surgery. There was a direct correlation between the level
      of NO and the activity of ACE and an inverse correlation between the content of
      NO and MDA in the sera taken from the cubital, internal jugular vein, and ICA
      before and after endarterectomy. There were significant increases in the level of
      NO, in the activity of ACE, and in the content of MDA and total cholesterol in
      the serum taken from the cubital vein before carotid endarterectomy, which is
      indicative of significant oxidative stress and the necessity of its pathogenetic
      correction.

PMID- 15449767
TI  - [Life quality in patients with early hypertensive disease].
AB  - Thirty-seven males aged 18 to 55 years (mean age 29.6 +/- 1.8 years) who had a 1
      3-year history of arterial hypertension (AH) were examined. All the patients were
      found to have grade 1 hypertension. Life quality (LQ) was studied using the
      questionnaire developed by the Ivanovo State Medical Academy in 2000. A
      significant decrease in LQ was found at the peak of AH in the patients as
      compared with healthy individuals; however, the specific parameters of the health
      status and reductions in their functional capacities differed slightly. It is
      concluded that it is necessary to apply a standardized approach to assessing the
      patients' complaints and medical history data.

PMID- 15449768
TI  - [Arterial hypertension in its concomitance with diseases requiring surgical
      treatment].
AB  - The paper deals with clinical and clinicoepidemiological analyses of arterial
      hypertension (AH) concurrent with surgical and gynecological pathology requiring
      surgical treatment. AH occurs in 30-50% of this category of patients, grades 1
      and 2 AH being most common. The presence of AH, inadequately treated AH in
      particular, increases the surgical and anesthesiological risks of the possible
      development of complications, such as hypertensive and hypotensive responses,
      cardiac arrhythmia, resistant AH, myocardial ischemia and infarction, cerebral
      circulatory disorders.

PMID- 15449769
TI  - [Automatic regulation and central hemodynamics in patients with postinfarct
      cardiosclerosis and heart failure].
AB  - The study was undertaken to examine the specific features of autonomic regulation
      and the parameters of central hemodynamics in patients with postinfarct
      cardiosclerosis (PICS) and circulatory insufficiency who had different types of
      left ventricular remodelling (LVR). Thirty-two patients with PICS and heart
      failure (HF) were examined. The autonomic status was studied, by analyzing
      cardiac rhythm variability (CRV) from 5-min resting cardiointervalograms and by
      the cardiovascular tests described by D. Y. Ewing; integral rheography was also
      performed. The patients were divided into 2 groups according to the type of LVR.
      Patients with PICS + HF and concentric LVR were found to have a more balanced
      autonomic circulatory regulation and a hemodynamic type that was more
      energetically efficient for the myocardium. Those with PICS + HF and eccentric
      LVR had a hemodynamic type that was less efficient for the myocardium, which was
      accompanied by the enhanced activity of the sympathetic nervous system (SNS) even
      at resting. Patients with PICS + HF, particularly in the presence of the latter's
      higher functional class and eccentric LVR, seemed to have desensitized
      adrenoceptors and impaired baroreflex activity, as appeared as no rise in
      peripheral vascular resistance with the enhanced sympathetic activity. The
      findings support the expediency of using beta-adrenoblockers in HF in patients
      with PICS, particularly with eccentric LVR. Analysis of cardiac rhythm
      variability is sufficiently informative in evaluating autonomic regulation and
      autonomic balance, SNS tone in particular, in patients with HF.

PMID- 15449770
TI  - [Assessment of a complex of external phenotypic signs for the detection of minor
      cardiac anomalies].
AB  - The external phenotypic features of the structure of connective tissue (CT) were
      determined in 120 patients (110 males and 10 females aged 18 to 30 years) with
      echocardiographic criteria for mitral prolapse and/or chordal malposition.
      Undifferentiated CT dysplasia (CTD) was established in 110 cases. Ten patients
      had differentiated CTD (Marfan's syndrome and the Ehlers-Danlos syndrome). A
      modified schedule including 63 indices was used to study the external phenotype.
      The external signs of dysplasia were detected in all the cases of
      echocardiographically verified CTD with a predominance of the manifestations of
      craniofacial dysmorphism. The maximum number of external CTD was ascertained in
      patients with differentiated CTD and in those with undifferentiated CTD who had
      an asthenic constitution and abnormal body weight deficiency. The number of
      external markers, which exceeds the threshold level (5), or the presence of 3-4
      morphodysplasias at various sites is considered to be diagnostically significant
      in detecting minor cardiac anomalies. The paper presents an algorithm for
      diagnosing cardiac microanomalies, which is based on the determination of the
      external signs of CTD.

PMID- 15449771
TI  - [Impact of photo hemotherapy on blood lipid composition in coronary heart
      disease].
AB  - The serum lipid composition (total cholesterol (TC), low-density lipoproteins
      (LDL), high-density lipoproteins (HDL), and triglycerides) was studied in 47
      patients with coronary heart disease (CHD) (Functional Classes II-IV) treated in
      the inpatient setting. A significant increase in the above parameters was found
      in 87% of the patients. During drug treatment, 28 patients received a course of
      photo hemotherapy (PHT), their blood was irradiated with blue light (Group 1). In
      another group, including 9 patients (Group 2), their blood underwent ultraviolet
      irradiation (UVI). A control group comprising 10 individuals received only drug
      treatment. In Group 1, there was a significant decrease in the levels of TC and
      LDL and an increase in the content of HDL. In Group 2, only the level of LDL
      decreased.

PMID- 15449772
TI  - [Temporal organization of external respiratory function in elderly patients with
      chronic obstructive lung disease].
AB  - The clinical course and the circadian, circaseptan, and circasemiseptan
      chronostructure of external respiratory function (ERF) were studied in 26 elderly
      patients with chronic obstructive lung diseases before and after routine therapy
      (RT). ERF was studied on a meta-test spirograph (Russia) and a Ferraris medical
      peak flowmeter (UK). The values of ERF and bronchial patency were measured every
      4 hours within 7 days before and after 10-day RT. The latter included euphylline,
      expectorants, and antibacterial drugs, if indicated. The patients also use "on
      demand" dosage aerosol inhalators not more than 3-5 times a day. The
      chronobiological data were analyzed by the averaged group cosinor test described
      by F. Halberg. The results of the study made it possible to detect the impaired
      temporary organization of ERF and bronchial patency, the phenomena of external
      and internal desynchronism both prior to and following RT. It clinical effect
      occurred on day 5.5 after RT. Before RT, circadian variations were found in
      respiratory volume (RV), respiratory minute volume (RMV), vital capacity (VC),
      forced expiratory value per sec (FEV1), the Tiffeneau test, and peakflowmetry.
      After RT, they remained other than variations in RV. The average daily values of
      VC, FEV1, Tiffeneau test, PO2, and KIO2 statistically significantly increased.
      The increases of MESORs and other indices tended to be significant.
      Circasemiseptan variations were found in RV, VC, and FEV1 before RT. After
      treatment, these were detected in respiration rate (RR), RMV, VC, and KIO2. The
      MESORs of RMV, VC, FEV1, and KIO2 statistically significantly increased. Prior to
      and following RT, there were virtually no 7-day (circaseptan) variations, other
      than those in RR before therapy. The MESORs of VC, FEV1, MVL, and RD
      statistically significantly increased. The MESORs of other parameters of ERF
      tended to be significant. Thus, RT led to the improved circadian and
      circasemiseptan organization of ERF and, to a lesser degree, to that of
      circaseptan chronostructure of the parameters of ERF.

PMID- 15449773
TI  - [The type of pain in duodenal peptic ulcer].
AB  - The paper presents the results of an examination of 269 patients (including 205
      males and 64 females) aged 18-62 years who had gastroduodenal ulcers; amongst
      them, 137 and 132 patients were treated in the in- and out-patient settings,
      respectively. It was ascertained that the pathomorphism of the clinical picture
      of peptic ulcer had occurred. About a third of all the exacerbations became
      asymptomatic or displayed few symptoms. In patients with duodenal ulcer, the
      epigastrium rather than the right hypochondrium is the most common site of pain
      on an exacerbation.

PMID- 15449774
TI  - [Comparative effectiveness of different methods of diagnosis and correction of
      impaired portal circulation].
AB  - The diagnostic effectiveness of X-ray radionuclide and ultrasound determination
      of portal blood flow and the impact of different treatments on the blood flow
      were evaluated in 76 patients with hepatic cirrhosis. The treatment regimens were
      used propranolol (Group 1), isosorbide-5-mononitrate (monosan) (Group 2), and a
      combined therapy with propranolol in combination with diuretics and a course of
      intravenous laser irradiation (Group 3). In terms of both clinical and laboratory
      parameters and the status of portal circulation, the highest effect was observed
      in the patients receiving the combined therapy.

PMID- 15449775
TI  - [Comparative characterization of hemostatic parameters in patients with cerebral
      stroke].
AB  - Two hundred and sixty-nine patients with cerebral stroke (CS), including 184
      patients with ischemic stroke and 85 with hemorrhagic stroke (HS), were examined.
      A control group consisted of 56 healthy individuals matched by sex and age. The
      status of different links of the hemostatic system was assessed in patients with
      CS, by using "Tekhnologiya-Standart" (Technology Standard) kits (Barnaul). The
      findings suggest the higher platelet aggregability with the universal aggregation
      inductor (ADP) and ristomycin, as well as suppressed fibrinolytic activity,
      elevated levels of soluble fibrin-monomeric complexes, and decreased
      concentrations of angiotensin III. The lupus anticoagulant causing a poor outcome
      of the disease was much more frequently detected in patients with HS.

PMID- 15449776
TI  - [Daily blood pressure profiles and endothelial functions during long-term
      treatment of arterial hypertension with angiotensin-converting enzyme
      inhibitors].
AB  - Clinical practice has been recently applied new approaches to classifying
      patients with arterial hypertension (AH), which are based on the determination of
      the summary risk suggesting the prognosis of the disease. This approach is quite
      efficient due to the fact that it takes into account a combination of the
      comparable clinical symptoms of AH, which characterize its course. The paper
      presents data on the values of blood pressure (BP) in AH and on daily BP profiles
      (DBPP) in 494 patients with different categories of a risk and on their
      endothelial function. It also gives the results of achievement of target BP
      levels in patients with AH having different categories of a risk during long-term
      (36-month) treatment with enapril and perindopril, as well as data on its impact
      on endothelial vasomotor function. The findings suggest that the higher the risk
      is, the more severe the hypertensive syndrome is; that the redistribution of DBPP
      occurs towards prognostically poor types and endothelial dysfunction (EDF)
      progresses. Treatment with angiotensin-converting enzyme (ACE) inhibitors results
      not only to the achievement of target BP levels and to the normalization of DBPP,
      but also to the amelioration of EDF. Moreover, the co-administration of ACE
      inhibitors and isosorbide-5-mononitrates causes additional antiischemic effects.

PMID- 15449777
TI  - [Aerobic and hemodynamic mechanisms of the antianginal effect of drugs in
      patients with angina pectoris].
AB  - Paired bicycle ergometric tests were performed to study the basic features of the
      aerobic hemodynamic mechanism of antianginal effects of reference representatives
      of the major classes of antianginal drugs (AADs) (nitrosorbide, corinfar,
      propranolol) in 54 patients with Functional Classes II-IV angina pectoris (AP).
      Oxygen consumption and central hemodynamic parameters were studied during
      exercise. The efficiency of a single administration of the drugs was 53-62%. In
      the context of the whole organism, AADs increased exercise tolerance in patients
      with AP, by optimizing oxygen-supplying processes: by reducing oxygen uptake, on
      the one hand, and by improving oxygen delivery to working organs, on the other.
      In so doing, corinfar-induced activation of the oxygen-transporting system
      resulted from the higher hemodynamic productivity; propanolol enhanced
      hemodynamic effectiveness, nitrosorbide showed a combination of both effects.

PMID- 15449778
TI  - [Food additive (bifeinol, detovit, squalenol) in the treatment of patients with
      metabolic syndrome].
AB  - For 2 months, 33 patients with the metabolic syndrome (MS) took a biologically
      active food additive as bifeinol, detovit, squalenol, which contained vitamins,
      minerals, essential amino acids, dietary cellulose, and a complex of
      polysaturated fatty acids. This yielded a positive result as decreases in body
      weight by 8%, in the levels of cholesterol, triglycerides, and low-density
      lipoproteins by 8.3, 27.8, and 9.3%, respectively. The food additive is
      recommended for the planned course use in patients with MS.

PMID- 15449779
TI  - [To the optimization of the diagnosis of primary ciliary dyskinesia].
AB  - Functional and morphological studies of the mucociliary system in primary ciliary
      dyskinesia were conducted using a model of the Zivert-Cartagener syndrome. They
      established the specific features of the mucociliary system and the expediency of
      a direct evaluation of mucociliary clearance by a non-invasive method in vivo, by
      taking into account the pronounced degree of mucociliary insufficiency. This
      makes it possible, no matter whether the situs inversus is absent or present, to
      reduce a cumbersome diagnostic complex usually used to verify this pathology and
      to undertake a study of the ultrastructure of bronchial epithelial cilia
      immediately. This approach enhances the accuracy of a diagnosis of this
      pathology, decreases its scope and time, and reduces its cost.

PMID- 15449780
TI  - [Computed tomography and study of external respiratory function in the diagnosis
      of complications due to chronic obstructive lung disease].
AB  - Forty patients with chronic obstructive lung disease (COLD) were examined.
      Determinations were made of pulmonary pressure (PP), by using Doppler
      echocardiography, lung tissue density (LTD) and the diameter of the pulmonary
      trunk (PT) from the data of computed tomography, as well as external respiratory
      function (ERF). An inverse correlation was found between LTD and the diameter of
      PT. Panlobular pulmonary emphysema occurring in 82.5% of the examined was
      characterized by decreased LTD less than (-) 930 Hounsefield units (HU) and a
      more than 40% increase in the RV/TLC ratio. In any severity of COLD, the values
      of PP were statistically significantly greater than those in the control group.
      In severe COLD, the diameter of PT exceeded that in healthy individuals. There
      was a statistically significant relationship of the values of ERF to LTD in 65%
      of the patients (with LTD of (-) 900 to (-) 1000 HU).

PMID- 15449781
TI  - [Experience with non-drug correction of autonomic disorders in adolescents].
AB  - The efficiency of recovery of autonomic imbalance by auricular electric
      neurostimulation (AENS) was studied. Thirty-nine children aged 11 to 15 years who
      had been diagnosed as having vegetative dystonia were divided into 2 groups:
      Group 1 (n = 18) received therapy with AENS; Group 2 (a control group) (n = 21)
      had the standard drug therapy. The study has indicated that AENS is more
      effectively than the standard therapy. In Group 1, clinical symptoms began
      ameliorating more early than in Group 2. According to instrumental data, positive
      changes were recorded in all the children in Group 1 and only in 57.2% in Group
      2. It is concluded that it is expedient to use AENS to correct autonomic
      imbalance.

PMID- 15449782
TI  - [F. P. Gaaz and the problems of medical ethics].

PMID- 15449783
TI  - Critical initiatives. Palliative care services complement, not contradict ICU
      care.

PMID- 15449784
TI  - Increased hours, more errors.

PMID- 15449785
TI  - Axillary hydroadenitis; an unusual cause of toxic shock syndrome.

PMID- 15449786
TI  - Polymyositis: rare complication of hepatitis B vaccination. An unusual cause of
      toxic shock syndrome.
AB  - Transient weakness of the legs developed in a 17 year-old male high school
      student three weeks after the initial injection of a hepatitis B vaccine.
      Seventeen days after the second injection of the vaccine, low-grade fever, a
      pruritic maculopapular rash appeared and weakness of the legs recurred. This was
      associated with elevation of the creatinine kinase to 2,406 U/L. The day after
      admission he became afebrile and in the subsequent four days the rash improved
      but leg weakness persisted. One-month later, muscle strength had returned; and
      the creatinine kinase had returned to normal levels. The only case of
      dermatomyositis associated with hepatitis B vaccination and the findings in the
      six reported cases of surface antigen-positive hepatitis associated with
      polyomyositis or dermatomyositis are briefly reviewed. Hepatitis B vaccination
      should be encouraged, but it is important to be aware that, rarely,
      dermatomyositis, polymyositis or neurovascular complications may occur.
      Polymyositis associated with the administration of the hepatitis B vaccine or
      with hepatitis B virus infection is a rare occurrence. A Medline Search performed
      from 1960 to January 2002 associating hepatitis B vaccine or hepatitis B virus
      with myopathy, myositis, polymyositis and dermatomyositis, showed only one case
      of dermatomyositis related to the hepatitis B vaccine, and six case reports
      relating polymyositis to hepatitis B virus infection. We present a case where a
      causal relationship between polymyositis and hepatitis B vaccination appears
      quite likely.

PMID- 15449787
TI  - Severe community-acquired pneumonia and sepsis caused by Burkholderia
      pseudomallei associated with flooding in Puerto Rico.
AB  - Burkholderia pseudomallei (melioidosis) is usually found in endemic areas of
      Southeast Asia and Northern Australia. However, a few cases of confirmed
      melioidosis indigenous to Puerto Rico and the Americas have been reported
      previously. We describe the occurrence of a B. pseudomallei infection in a female
      with insulin-dependent diabetes mellitus exposed to flood waters in Puerto Rico.
      We conclude that B. pseudomallei should be considered a potential pathogen in
      high-risk patients with severe community-acquired pneumonia and sepsis in Puerto
      Rico especially in individuals exposed to flood waters during rainy seasons. A
      more thorough epidemiologic and microbiologic surveillance with environmental
      sampling may be warranted in the island.

PMID- 15449788
TI  - Some usual and unusual poisonings due to carbon monoxide.
AB  - Carbon monoxide poisoning is a frequent occurrence in both developed and under
      developed countries of the world. Carbon monoxide can be produced in fires,
      automobile engine exhausts and the incomplete combustion of organic matter. It is
      a "silent killer" that initially produces a mild progressive frontal headache,
      drowsiness and sleep that is usually ignored as common place. Continued low-level
      CO exposure for a long period of time in a confined space is cumulative and these
      accidental deaths are frequent but should be avoidable. Several usual and unusual
      poisonings are reported to illustrate its various forms of exposure. It all began
      many years ago when a bolt of lightening hit a fallen tree and produced a fire.
      Early cave man later learned to enjoy some of the benefits of this new discovery.
      They could now see at night, they could keep warm, keep the predators at bay,
      cook their food and make it taste better and be more gentle to their teeth. Also
      meat could be preserved and eaten at a later date especially if it were dried and
      smoked. They learned by trial and error that it was dangerous to bring their fire
      deep into their cave without a chimney. Carbon monoxide (CO) also can be easily
      produced by many other sources besides fire. Very common today is the incomplete
      combustion of gasoline in the engine of an automobile which can produce about 6%
      carbon monoxide.

PMID- 15449789
TI  - Headache profile at a medical institution with a specialized center for headache
      management.
AB  - OBJECTIVE: To describe the clinical characteristics of headache to determine the
      distribution of antimigraine medication use by specialty of treating physician
      and the cost of the treatment of headache, among suffers by type of employee
      (health professionals vs. others). BACKGROUND: The services of a Headache Center
      are usually offered to the employees of the hospital in which the Center is
      localized; however, the number and related outcomes of employees who use the
      Center services versus those who use primary care facilities remain unknown in
      Puerto Rico. METHODS: A self-administered questionnaire was completed by 350 out
      of 415 (84.3%) employees of one of the private hospital in San Juan, Puerto Rico
      regarding their management of headache. The data collected included age, gender,
      occupation, headache intensity and frequency, type of treating physician and
      medication use. Contingency tables were used to describe statistical associations
      among categorical variables. Pearson's chi square test or Fisher's exact test was
      used to assess significance. RESULTS: Nearly 75% of employees suffers headaches
      on a regular basis. Among these, 25% classified the headache as severe, 20.3% had
      5 or more attacks per month, 62.1% reported that productivity was affected and
      85% lost 1-2 days of work per month due to headache attacks. Approximately 20%
      visit a physician when they suffer a headache, and more than one-third visits a
      specialist. Only 2.34% of the employees used antimigraine medications (triptans).
      The use of triptans was more common among those employees attending a specialist
      for headache treatment than those attending primary care physicians (p < 0.05). A
      similar finding was observed for employees attending a neurologist versus other
      physicians (p < 0.05). CONCLUSIONS: These results indicate that headache attacks
      are prevalent and affect productivity and the cost for this institution was near
      dollars 4,400.00 per month. Despite the frequency and intensity of headache, less
      than one-fourth seek medical evaluation. Prescription ofspecific antimigraine
      medication was more common among specialists suggesting a more aggressive
      management for headache.

PMID- 15449790
TI  - [Adverse effects and interactions of medicinal herbal products].
AB  - The use of medicinal products derived from plants (phytomedicinals) has been
      increasing dramatically in the past years this has forced the health professional
      to increase their knowledge in the risks and benefits in the use of such
      products. This article reviews the most important adverse effects and
      interactions from the phytomedicinals and presents this information in the
      perspective of a responsible Integrative Medicine practice focused in achieving
      optimal therapeutic goals.

PMID- 15449791
TI  - Management of urinary tract infections, decubitus ulcer and pneumonia in the
      aging person.
AB  - Infections in the older person are common and a significant cause of morbidity
      and mortality. Infections of the urinary tract, skin and soft tissue infections
      including decubitus ulcers, antibiotics associated diarrhea and lower respiratory
      tract infections are particularly important in the elderly because of their
      frequency. While most initial antibiotic therapy is empiric, its important before
      treatment to try to document the etiology for better use of antibiotics.
      Infections of the urinary tract are frequently and potentially serious in the
      elderly, they must be separated from asymptomatic bacteriuria that requires no
      therapy. Upper and lower urinary tract infections are frequently caused by
      aerobic gram negative bacilli and or enterococci. Most authors prefer the use of
      fluoroquinolones to manage such infections. The elderly with decubitus ulcer
      presents a problem in management, since these are frequent polymicrobic
      infections in which anaerobes play an important role. The initial therapy usually
      involves the combination of a fluoroquinolone plus an antianaerobic agent like
      clindamycin. C. difficile diarrhea as frequent in nursing home residents as well
      as the older person with prior antibiotics. The treatment should be with
      metronidazole and avoid the use of vancomycin. Pneumonias in the elderly can be
      acquired in the community, the nursing home or during a hospitalization. The
      etiologic agents that predominate change from S. pneumoniae and atypicals in
      those from the community to an increase in gram negative pneumonia. The initial
      treatment as started by most authors as well as guidelines include the use of a
      new fluoroquinolone like gatifloxacin alone or in combination with a beta
      lactamic agent like ceftriaxone. For those infections acquired in the hospital
      therapy with third or fourth generation cephalosporins, carbapenems, beta-lactams
      with betalactamase inhibitors alone or in combination with an aminoglucoside and
      or vancomycin if MRSA is suspected is accepted therapy.

PMID- 15449792
TI  - [Severo Ochoa de Albornoz y Perez, M.D. Nobel prize of physiology and medicine
      and his relations to Puerto Rico].

PMID- 15449793
TI  - [Severo Ochoa and the RNA].

PMID- 15449794
TI  - 15th Annual Convention American College of Cardiology Puerto Rico Chapter May 28
      30, 2004 Ritz Carlton Hotel, San Juan, Puerto Rico.

PMID- 15449795
TI  - Wanted: mission-driven workplaces.

PMID- 15449796
TI  - Self-healing practices: essential tools for balance.

PMID- 15449797
TI  - On the road again.

PMID- 15449798
TI  - Florence Nightingale: INTJ at work.

PMID- 15449799
TI  - Renewing the spirit: sanctuaries for healing.

PMID- 15449800
TI  - Mentoring: link to the future.

PMID- 15449801
TI  - For the children (and others in desperate need around the world).

PMID- 15449802
TI  - Career coaching.

PMID- 15449804
TI  - Out of pain, compassion.

PMID- 15449803
TI  - Nurse-managed, community-based care.

PMID- 15449805
TI  - Feasibility of fiberoptic bronchoscopy for small infants including newborns.
AB  - In pediatric practice, the application of fiberoptic bronchoscopy (FBS) has been
      limited to infants and children, primarily because the caliber of the available
      fiberscopes was too large for application to small babies including newborns.
      Recently, fiberscopes with thinner calibers were generated, prompting application
      of FBS to newborn patients. In the recent five years, we have utilized narrow
      caliber FBS at the Neonatal Intensive Care Unit of the Tokai University Hospital.
      Through 21 FBS applications on newborn patients for various indications, we
      conclude that given careful monitoring of the patient's systemic conditions and
      management of ventilation, FBS can be safely applied on small babies including
      newborn patients and facilitate treatment of the airway problems.

PMID- 15449806
TI  - Platelet inhibition by single low-dose aspirin, using the newly developed
      aggregometry with the laser light scattering method.
AB  - Low-dose aspirin (acetylsalicylic acid 81 mg/day, LDA) is often used as an
      antiplatelet drug in the treatment of cardiovascular and cerebrovascular diseases
      as well as for patients with anti-phospholipid antibody syndrome. In this study,
      we explored the duration of the inhibitory effect of a single LDA on platelet
      aggregation, using the newly developed aggregometry with the laser light
      scattering method. Five healthy volunteers (females between 23 and 30 years old)
      ingested 81 mg of buffered aspirin. Platelet aggregation was measured with
      adenosine 5'-diphosphate before the ingestion and at the 1st, 2nd, 4th, 6th, and
      8th day thereafter. The results showed that the effect of 81 mg of aspirin
      continues for at least 8 days, which suggested that the intermittent
      administration of 81 mg of aspirin (a few times a week) might be an alternative
      way to induce the anti-platelet effect.

PMID- 15449807
TI  - A case report of intraocular lens luxation with the capsular bag after
      vitrectomy.
AB  - We experienced a case of intraocular lens (IOL) luxation with the capsular bag
      after vitrectomy. The case was a 66-year-old female in whom an IOL was implanted
      one year after surgery for giant tear retinal detachment using silicone oil. Four
      years after the implantation surgery, the patient suffered subluxation of the IOL
      with the capsular bag. Examinations of the luxated IOL with the capsular bag
      using a stereoscopic microscope confirmed the presence of silicone oil droplets
      between the capsule and the IOL. Adhesion of vitreous body residues was observed
      in the capsule. Luxation of the IOL was thought to be connected with chronic
      inflammation resulting from the use of silicone oil and repeated vitrectomy. In
      addition to examining pathological findings of luxated IOL, it would also be
      important in the future to identify the pathology of the capsular bag.

PMID- 15449808
TI  - A method using sutures for extraction of subluxated posterior chamber intraocular
      lens and transscleral fixation: spider technique.
AB  - We experienced 5 cases with intraocular lens (IOL) subluxation in which IOL
      extraction was safely conducted using two 10-0 polypropylene sutures through pars
      plana and proceeded with secondary IOL implantation using the same sutures. This
      is a report on our study of this safe method for IOL extraction and fixation
      method. The method is developed from ab externo sulucus fixation. Usage of two 10
      0 polypropylene sutures originally placed for the second fixation enables a
      surgeon to hold subluxated IOL and prevents it from falling into the vitreous
      body cavity. A 6-mm incision is made in the corneal limbus, and the IOL is
      removed. Using the two 10-0 sutures that are already in place, secondary IOL
      implantation can be conducted at one time. There were no cases of postoperative
      retinal detachment. Postoperative visual acuity was improved in all cases. No
      dislocation was seen in any of the cases with the pupils dilated.

PMID- 15449809
TI  - The effect of alpha2-agonist on IOP rise following Nd-YAG laser iridotomy.
AB  - We have tested the effect of topical administration of 0.5% para-amino-clonidine
      (PAC), an adrenergic alpha 2 agonist, on intraocular pressure (IOP), protein and
      prostaglandin E2 (PGE2) concentration in aqueous humor following the laser
      application to the iris of albino rabbits. The irides received Q-switched Nd: YAG
      laser irradiation with the energy level ranging from 2 to 80 mJ with and without
      topical administration of PAC one-hour prior to and immediately following laser
      irradiation. The IOP was measured with an Alcon pneumotonometer prior to and
      hourly for 6-hours following laser application. Aqueous humor was withdrawn prior
      to and at 0.5, 1, 2, 4 hours following laser irradiation for determining protein
      (Lowry method) and PGE2 (radioimmunoassay). Four to 6 rabbits were used for each
      experiment. The increase in IOP, protein and PGE2 concentration following laser
      irradiation was demonstrated to be dependent on the amount of laser energy. PAC
      significantly suppressed the IOP rise and the elevation of protein content, while
      it failed to affect the increase in PGE2.

PMID- 15449810
TI  - The nature and limits of the physician's professional responsibilities: surgical
      ethics, matters of conscience, and managed care.
AB  - The nature and limits of the physician's professional responsibilities constitute
      core topics in clinical ethics. These responsibilities originate in the
      physician's professional role, which was first examined in the modern English
      language literature of medical ethics by two eighteenth-century British physician
      ethicists, John Gregory and Thomas Percival. The papers in this annual clinical
      ethics number of the Journal explore the physician's professional
      responsibilities in the areas of surgical ethics, matters of conscience, and
      managed care.

PMID- 15449811
TI  - Informed consent and surgeons' performance.
AB  - This paper argues that the provision of effective informed consent by surgical
      patients requires the disclosure of material information about the comparative
      clinical performance of available surgeons. We develop a new ethical argument for
      the conclusion that comparative information about surgeons' performance-
      surgeons' report cards--should be provided to patients, a conclusion that has
      already been supported by legal and economic arguments. We consider some recent
      institutional and legal developments in this area, and we respond to some common
      objections to the use of report cards on the clinical performance of surgeons.

PMID- 15449812
TI  - Presumed consent, autonomy, and organ donation.
AB  - I argue that a policy of presumed consent for cadaveric organ procurement, which
      assumes that people do want to donate their organs for transplantation after
      their death, would be a moral improvement over the current American system, which
      assumes that people do not want to donate their organs. I address what I take to
      be the most important objection to presumed consent. The objection is that if we
      implement presumed consent we will end up removing organs from the bodies of
      people who did not want their organs removed, and that this situation is morally
      unacceptable because it violates the principle of respect for autonomy that
      underlies our concept of informed consent. I argue that while removing organs
      from the bodies of people who did not want them removed is unfortunate, it is
      morally no worse that not removing organs from the bodies of people who did want
      them removed, and that a policy of presumed consent will produce fewer of these
      unfortunate results than the current system.

PMID- 15449813
TI  - No safe harbor: the principle of complicity and the practice of voluntary
      stopping of eating and drinking.
AB  - In recent years, a number of writers have proposed voluntary stopping of eating
      and drinking as an alternative to physician-assisted suicide. This paper calls
      attention to and discusses some of the ethical complications that surround the
      practice of voluntary stopping of eating and drinking. The paper argues that
      voluntary stopping of eating and drinking raises very difficult ethical
      questions. These questions center on the moral responsibility of clinicians who
      care for the terminally ill as well as the nature and limits of the authority
      they exercise over them.

PMID- 15449814
TI  - Conscientious refusal and a doctors's right to quit.
AB  - Patients sometimes request procedures their doctors find morally objectionable.
      Do doctors have a right of conscientious refusal? I argue that conscientious
      refusal is justified only if the doctor's refusal does not make the patient worse
      off than she would have been had she gone to another doctor in the first place.
      From this approach I derive conclusions about the duty to refer and facilitate
      transfer, whether doctors may provide 'moral counseling,' whether doctors are
      obligated to provide objectionable procedures when no other doctor is available,
      why the moral consensus among doctors seems relevant even though it does not
      determine whether something is morally acceptable, and whether doctors should
      stay out of fields whose standard procedures they find morally unacceptable.

PMID- 15449815
TI  - Therapeutic doubt and moral dialogue.
AB  - This paper aims at analysing the problem of remainder and regret in moral
      conflicts. Four different approaches are subject of investigation: a moral
      theoretical strategy aimed at consistency; a narrative approach of moral
      coherence and open consensus; Plato's moral methodology of dialogue and aporetic
      resolution of moral conflicts and finally, an approach deduced from Greek tragedy
      of emotional resolution of moral conflicts. A central argument is that since
      there exists no theoretically convincing way of solving the problem of remainder
      and regret, the attention should instead be directed towards finding alternative
      ways of coping with this problem. The three last approaches subject of
      investigation attempt--each in their own way--to do this. Teaching medical ethics
      to medical students and the burning issue of medical fallibility is used to
      demonstrate the relevance of these forms of resolution in a medical context.

PMID- 15449816
TI  - Beyond health care accountability: the gift of medicine.
AB  - E. Haavi Morreim's book, Holding Health Care Accountable, insightfully describes
      several features of the current crisis in malpractice in relation to the health
      care marketplace. In this essay, I delineate the key and eminently practical
      guide for reform that she lays out. I argue that her insights bring us to more
      fundamental aspects than immanent medical economy and accountability--aspects
      that are ignored at present. I describe the features of immanent economy and how
      they tend to cover over epistemological and existential finitude in medicine,
      show how economy can in fact create new medical knowledge, and show that
      necessary error is a real feature of day-to-day medical practice. The current
      system, even with Morreim's reforms, remains at the level of immanent economy,
      but with modifications may point to the features of medicine that transcend
      medical knowledge and economy. The gifts of medicine cannot be reduced to the
      immanent medical economy, and any attempt to do so results in crisis. A health
      care that points to finitude and fallibility is one that points to the mystery of
      human existence and mortality. Any health care financing system that helps to
      delineate finitude--both epistemological and existential--is one that will give
      patients a new lease on living and dying.

PMID- 15449817
TI  - Contraceptive use and behavior in the 21st century: a comprehensive study across
      five European countries.
AB  - OBJECTIVE: The choice of currently available contraceptive methods has increased
      considerably in recent years, offering women of reproductive age a variety of
      different methods dependent on their needs and lifestyle. In order to determine
      the pattern of use of current methods in contraception, a survey was conducted in
      a large population of women drawn from five European countries (France, Germany,
      Italy, Spain and the United Kingdom). METHOD: More than 12,000 randomly selected
      women, aged 15-49 years, were interviewed using a standardized questionnaire
      which addressed the use of current methods of contraception. The responses were
      analyzed for the total study population, and, where appropriate, by country and
      age. RESULTS: An oral contraceptive (OC) was confirmed as the most widely used
      method of contraception for women in the European study population, with an
      estimated 22 million users in the five countries. Women using an OC reported very
      high levels of satisfaction (>90%). Male and female sterilization were the main
      methods of contraception in women aged 40 years and older. One-half of the women
      had undergone their sterilization before the age of 35 years. More than 50% of
      the women who had undergone sterilization had not been adequately informed and
      counselled about alternative reversible contraceptive options. No method of
      contraception was being used currently by 23% of the European study population,
      and unreliable methods of contraception (including cap/diaphragm, chemical, and
      natural and withdrawal methods) were being used by a further 6% of the
      population. Although valid reasons (e.g. not in a sexual relationship, wish to
      become pregnant) were given by many women who were not using contraception, there
      still remains a large number of women who need counselling regarding the
      importance of using reliable contraceptive methods. The number of women aged 15
      49 years in the five European countries who are considered at risk of an unwanted
      pregnancy is estimated to be 4.7 million (6.5%). CONCLUSIONS: Differences in the
      use pattern of contraceptive methods were demonstrated that emphasize the social
      and cultural differences between the countries. The findings in the current study
      can be used as a baseline from which to monitor trends in contraceptive use and
      behavior in subsequent studies.

PMID- 15449818
TI  - The condom in relation to prevention of sexually transmitted infections and as a
      contraceptive method in Sweden.
AB  - OBJECTIVE: To analyze in detail the latest Swedish population survey regarding
      condom use in order to gain a deeper knowledge of the characteristics of women
      and men using or not using condoms at a time when the number of sexually
      transmitted infections (STIs) had started to increase. METHODS: From a population
      based survey of sexual life in Sweden among men and women aged between 18 and 74
      years (n = 2810), we investigated the use of condoms in relation to social
      demographic, lifestyle, sexual and behavioral characteristics. RESULTS: In the
      age group 18-49 years, every third person had experience of a legal abortion and
      every fourth had had an STI. Overall, use of condoms was 12% in the whole
      population and 15% in the age group 18-49 years. Using a condom as a method of
      contraception, as opposed to other methods, was found to be less frequent in six
      subgroups: when coitus was less frequent, age above 25 years, among those who had
      had many partners and those with earlier experience of abortion or STI, as well
      as having a risky behavior. Using a condom as a preventive against contracting an
      STI occurred less often in women and men older than 25 years and among those
      having coitus more frequently. CONCLUSION: Even with good information and easy
      accessibility to condoms, there are still obstacles to their use. To achieve the
      aim of safer sexual practice, it is a challenge for the couple as well as for
      counselors to reason about the advantages and disadvantages of not using a
      condom. Discussions about attitudes, behavior and gender differences must be
      continued and emphasized in coming generations, both on the individual and on a
      societal level, in order to achieve safer sexual practice.

PMID- 15449819
TI  - Family planning in the Southeast Anatolian Project Region.
AB  - OBJECTIVES: The aim of this study was to evaluate contraceptive use by women of
      reproductive age in the Southeast Anatolian Project Region and the promotion of
      the use of family planning services. METHODS: An optimum sample size to represent
      the rural and urban area of the region was determined and the sample was chosen
      by sampling method proportional to the size. A total of 1126 houses were visited
      and questions about reproductive health were asked of 1019 ever-married
      (currently married, widows and divorced) women. RESULTS: The study showed that
      48.2% of the ever-married women of reproductive age had never used any method of
      family planning; 37.4% were currently using a family planning method, and 14.4%
      had used a family planning method in the past. Of the women who were currently
      using a family planning method, 73.1% were using an effective method. The result
      of the logistic regression analysis showed that educational level, knowledge of
      Turkish, type of residence, and total number of living children were the main
      variables that affected the use of family planning methods. CONCLUSIONS: Use of
      family planning methods in the region was not at the expected level. In order to
      decrease the barriers to family planning in developing countries, we must provide
      obtainable, acceptable, integrated health services.

PMID- 15449820
TI  - Cytomegalovirus excretion in pregnant women in the eastern Black Sea region of
      Turkey.
AB  - AIM: The study was carried out to determine the viral excretion rate of
      cytomegalovirus (CMV) in pregnant women in the eastern Black Sea region of
      Turkey, and to observe how it compared with that in western countries. METHOD:
      Cervical excretion of cytomegalovirus by pregnant women was studied employing a
      highly sensitive CMV detection assay supported with fluorescent labeled
      monoclonal antibody directed against an immediate early antigen, known as DEAFF
      (detection of early antigen by fluorescent foci assay) test. RESULTS: CMV
      excretion rates during the third trimester of pregnancy were similar to the
      detection rates reported from most developed countries. Our results also showed
      that the rate of cervical CMV excretion was higher among pregnant women who had a
      history of more than one spontaneous abortion.

PMID- 15449821
TI  - Resistance against contraception or medical contraceptive methods: a qualitative
      study on women and men in Istanbul.
AB  - OBJECTIVES: This research was carried out to reveal the attitudes of men and
      women about contraception in the Umraniye district of Istanbul. METHODS: Focus
      group discussions were used for data collection. Data from 20 groups of married
      people (ten groups of men and ten of women) living in Umraniye were analyzed.
      RESULTS: Most people attending the focus groups in the study were against having
      'too many' children. Economic constraints appear to be a leading influencing
      factor for limiting the number of children. Urbanization also seems to have a
      strong influence on people's knowledge and attitudes about contraception. Culture
      and religious beliefs were not found to be major barriers to contraception in
      general, but they would influence the selection of the type of a certain
      contraceptive method. More specifically, culture and religious beliefs were
      barriers to use of medical methods, and they were the main reasons for use of the
      withdrawal method, which is the most common method used in Turkey. CONCLUSIONS:
      Men and women are not resistant to contraception, but they are reluctant to use
      medical methods. The provision of contraceptive services, with special attention
      to cultural and religious beliefs and values, and the inclusion of appropriate
      counseling and education sessions during service delivery, may give clients new
      options and increase the use of medical methods.

PMID- 15449822
TI  - Knowledge and attitudes towards emergency contraception of health-care providers
      in a region with a high birth rate.
AB  - OBJECTIVE: To assess the knowledge of, attitude towards and practices of
      emergency contraception among health-care providers at a university hospital
      located in a region with a high birth rate. METHODS: The survey was conducted
      among 214 health-care providers working at a university hospital located in
      eastern Turkey. RESULTS: Two hundred participants completed the questionnaire. Of
      the respondents, 26.0% said that they did not know anything about emergency
      contraception, while the remaining 74.0% said that they knew about at least one
      of the methods of emergency contraception. But among these, the knowledge of
      38.5% of the participants about emergency contraception was accurate and that of
      61.5% was inaccurate. Thirty-four percent of the respondents stated that they had
      previously required personally to use emergency contraceptive methods. The most
      commonly used emergency contraceptive methods were oral contraceptives (69.1%)
      and intrauterine device (14.7%). None of the respondents knew anything about
      mifepristone and levonorgestrel. CONCLUSION: There is a knowledge deficit among
      health-care providers who play a significant role in the dissemination of the
      information about emergency contraception.

PMID- 15449823
TI  - The role of combined oral contraceptives in the management of acne and seborrhea.
AB  - Acne and seborrhea (or facial oiliness) are related androgenic skin disorders
      which affect a high proportion of women after menarche. They can have a negative
      effect on psychological well-being and social life. Androgens play an important
      role in the pathogenesis of acne through the stimulation of sebum secretion,
      increasing sebaceous gland size and possibly through follicular
      hyperkeratinization. Conversely, estrogens decrease sebum production by
      suppressing gonadotropin release and androgen production and increasing sex
      hormone binding globulin production. One of the treatment options for these
      conditions is hormonal therapy, especially for women who require contraception.
      The effect of combined oral contraceptives in androgenic skin disorders depends
      on their estrogen:progestogen balance and on the antiestrogenic activity of the
      progestogen component. Improved understanding of what women value about oral
      contraceptives suggests that the choice of product should be tailored as much as
      possible to the individual. Several combined oral contraceptives containing new
      generation progestogens (e.g. desogestrel, gestodene) or progestational
      antiandrogens (e.g. cyproterone acetate, chlormadinone acetate) have demonstrated
      efficacy in the treatment of women with acne, although comparisons between trials
      are difficult because of differing endpoints. Seborrhea has been less well
      studied, but the few studies that are available show an improvement in women with
      this condition using combined oral contraceptives.

PMID- 15449824
TI  - Redescription of Pleorchis polyorchis (Stossich, 1889) (Digenea:
      Acanthocolpidae), a rare and poorly known parasite of the intestine of Sciaena
      umbra l. (Perciformes: Sciaenidae) from the western Mediterranean Sea.
AB  - Pleorchis polyorchis (Stossich, 1889), the type-species of the genus, is
      described on the basis of new material from Sciaena umbra from off Corsica,
      France. This is only the second description of this species. The results of this
      study indicate that there are apparent errors in the original description in
      relation to the number of testes, the anterior limit of the vitellarium, the
      extent of the post-testicular field and the shape of the intestinal caeca, and
      that the type-species is closer to its congeners than previously believed. P
      polyorchis is compared with other nominal species of the genus, and species
      previously attributed to the genus are commented upon.

PMID- 15449825
TI  - New feather mite taxa of the Rhytidelasma Gaud, 1966 generic group (Astigmata:
      Pterolichidae) from the red-flanked lorikeet Charmosyna placentis placentis
      (Psittacidae).
AB  - Two new genera and species related to Rhytidelasma Gaud, 1966 and Lorilichus
      Atyeo & Gaud, 1991 are described from the plumage of the red-flanked Lorikeet
      Charmosyna placentis placentis (Temminck) (Psittacidae). These are Ceratolichus
      mirabilis n. g., n. sp. and Charmosylichus anamphiestos n. g., n. sp. In
      addition, an improved diagnosis of Lorilichus is proposed and two new species of
      this genus are described from the red-flanked lorikeet, L. longiphallos n. sp.
      and L. paralobiger n. sp.

PMID- 15449826
TI  - Molecular and morphological comparisons between Gyrodactylus ostendicus n. sp.
      (Monogenea: Gyrodactylidae) on Pomatoschistus microps (Kroyer) and G. harengi
      Malmberg, 1957 on Clupea harengus membras L.
AB  - Gyrodactylus ostendicus n. sp. was exclusively found on fins of the common goby
      Pomatoschistus microps (Kroyer). The haptoral hard parts are among the smallest
      described for species of Gyrodactylus. A presumed similarity between the new
      species and G. harengi Malmberg, 1957 (subgenus Metanephrotus Malmberg, 1964)
      encouraged a comparative approach. A morphological analysis showed the marginal
      hook sickles of G. ostendicus to be of quite a different type and similar to
      those of G. arcuatus Bychowsky sensu Bychowsky & Poljansky (1953) (subgenus
      Mesonephrotus Malmberg, 1964). The new species has a pharynx with short
      pharyngeal processes. Its protonephridial system has small bladders, indicating
      an association with the subgenera Mesonephrotus or Metanephrotus. Molecular
      phylogenetic analyses, including all of the species of Mesonephrotus and
      Metanephrotus currently available on the GenBank database, suggested that the new
      species belongs to Mesonephrotus. Combined morphological and molecular studies of
      the new species show that G. ostendicus is more closely related to G. arcuatus
      than to G. harengi.

PMID- 15449827
TI  - Neotropical Monogenoidea. 46. Three new species from the gills of introduced
      aquarium fishes in India, the proposal of Heterotylus n. g. and Diaphorocleidus
      n. g., and the reassignment of some previously described species of Urocleidoides
      Mizelle & Price, 1964 (Polyonchoinea: Dactylogyridae).
AB  - Three new species of the Dactylogyridae are described from aquarium fishes
      collected in India and two new genera are proposed: Heterotylus heterotylus n.
      g., n. sp. from Hypostomus sp. (Loricariidae), Diaphorocleidus armillatus n. g.,
      n. sp. from Gymnocorymbus ternetzi (Characidae) and Urocleidoides vaginoclaustrum
      n. sp. from Xiphophorus helleri (Poeciliidae). Heterotylus n. g. is characterised
      by species having overlapping gonads (testis posterodorsal to the ovary), a mid
      ventral vaginal aperture, a copulatory complex consisting of a relatively
      straight copulatory organ unarticulated to a complex accessory piece, erect acute
      hook thumbs, unexpanded hook shanks, dorsal and ventral anchor/bar complexes and
      absence of well-defined basal roots of the ventral anchors. Diaphorocleidus n. g.
      includes species with overlapping gonads (testis posterodorsal to the ovary),
      submarginal sinistral vaginal pore, a copulatory complex comprising a coiled
      (counterclockwise) copulatory organ unarticulated to an accessory piece,
      protruding depressed hook thumb, hook shank with two subunits (proximal subunit
      expanded), dorsal and ventral anchor/bar complexes and V-shaped bars. The
      following new combinations are proposed: D. affinis (Mizelle, Kritsky & Crane,
      1968) n. comb. (syn. U. affinis Mizelle, Kritsky & Crane, 1968), D. kabatai
      (Molnar, Hanek & Fernando, 1974) n. comb. (syn. U. kabatai Molnar, Hanek &
      Fernando, 1974) and D. microstomus (Mizelle, Kritsky & Crane, 1968) n. comb.
      (syn. U. microstomus Mizelle, Kritsky & Crane, 1968).

PMID- 15449828
TI  - Redescriptions of Magnibursatus blennii (Paggi & Orechhia, 1975) n. comb. and
      Arnola microcirrus (Vlasenko, 1931) (Digenea: Derogenidae) from marine teleosts
      off Corsica.
AB  - Two species of halipegine derogenids are redescribed in detail from marine fishes
      off Corsica. Following a study of specimens from blennies off Corsica and museum
      material, Tyrrhenia Paggi & Orecchia, 1975 is considered to be a synonym of
      Magnibursatus Naidenova, 1969, and its type-species, T blennii Paggi & Orecchia,
      1975, is transferred to the latter genus as M. blennii (Paggi & Orecchia, 1975)
      n. comb. M. blennii differs from all species of Magnibursatus in possessing
      suckers of a similar size, numerous uterine loops in the forebody, and a sinus
      sac which is small in relation to the forebody and which has relatively thin,
      muscular walls. This species is recorded from Salaria pavo (Risso), Paralipophrys
      trigloides (Valenciennes) and Parablennius sp. and distinguished from similar
      species of the genus. Arnola microcirrus (Vlasenko, 1931) is recorded from Boops
      boops (L.), which appears to be its main host off Corsica, Diplodus sargus (L.),
      D. annularis (L.) and Spondyliosoma cantharus (L.). The material from Corsica is
      compared with previous descriptions and material of this species, and differences
      were considered to be within the bounds of intra-specific variation.

PMID- 15449829
TI  - Parachordodes tegonotus n. sp. (Gordioidea: Nematomorpha), a hairworm parasite of
      ground beetles (Carabidae: Coleoptera), with a summary of gordiid parasites of
      carabids.
AB  - A new species of hairworm, Parachordodes tegonotus n. sp. (Gordioidea:
      Nematomorpha) is described from three species of ground beetles (Carabidae:
      Coleoptera) from the state of Oregon. This is the first record of Parachordodes
      Camerano parasitising carabid beetles in North America. Diagnostic characters for
      the new species include size, colour, the nature and arrangement of the areoles,
      and the character, shape and extant of ornamentation on the ventral surface of
      the male tail. Encysted hairworm larvae found in the internal tissues of mayfly
      and caddisfly larvae at the type-locality were presumed to be those of P.
      tegonotus, indicating an indirect life-cycle involving paratenic hosts. A
      worldwide host list shows that some 70 species of ground beetles have been
      documented as developmental hosts to hairworms belonging to at least five genera,
      namely Gordius, Parachordodes, Dacochordodes, Gordionus and Paragordionus.

PMID- 15449830
TI  - Echinorhynchus salmonis Muller, 1784 (Acanthocephala: Echinorhynchidae) from the
      Bothnian Bay, Baltic Sea: morphological variability and radial asymmetry of
      proboscis hooks.
AB  - Echinorhynchus salmonis is a common parasite of salmoniform and other fishes,
      occurring in fresh and brackish waters throughout the Holarctic. Presented here
      is the first analysis of the morphometric and meristic variation in a Palaearctic
      population of E. salmonis, collected from whitefish Coregonus lavaretus L. and
      smelt Osmerus eperlaus (L.) from the Bothnian Bay, northern Baltic Sea.
      Morphological data were compared with published descriptions of congeneric taxa.
      Nearctic populations of salmonid echinorhynchids considered by some to represent
      a distinct species, E. coregoni Linkins in Van Cleave, 1919, did not show any
      morphological divergence from Palaearctic populations, indicating that the name
      E. coregoni should be suppressed. Similarly, E. alpinus Linstow, 1901 has been
      considered to be a junior synonym of E. salmonis. However, E. alpinus should be
      regarded as a valid species, because it has a longer and more elongate body. The
      armature of the acanthocephalan proboscis typically displays radial symmetry.
      However, in E. salmonis the hooks on the dorsal surface of the proboscis are
      smaller than those on the ventral surface. Size differences between dorsal and
      ventral hooks are most pronounced at the base of the proboscis. The systematic
      and functional significance of radial asymmetry of proboscis hooks is discussed.

PMID- 15449831
TI  - Promotion of private veterinary practice in Ghana: perceptions of veterinarians
      and veterinary technicians.
AB  - A study was designed to identify factors perceived by veterinarians and
      veterinary technicians as likely to promote private veterinary practice in Ghana.
      The participatory appraisal approach was used. The response rates were 88% (n =
      90), 100% (n = 9) and 86% (n = 200) for government field veterinarians, private
      veterinarians and government veterinary technicians, respectively. Significant
      proportions of government field veterinarians (67%, n = 79), and veterinary
      technicians (64%, n = 167) were willing to go into private practice if the
      necessary push was given. Factors perceived as likely to motivate them to go into
      private practice included availability of capital to cover start-up costs;
      provision of a vehicle; prospect of higher income; availability of loans with low
      interest rates; availability of credit facilities from suppliers; stable
      macroeconomic environment with low interest and inflation rates; high pet,
      poultry and livestock populations at locations earmarked for private practice;
      leasing of vacant government premises for use as clinic and for accommodation;
      and enforcement of legislation on private practice, especially that against
      moonlighting by government veterinarians and technicians. These should be
      considered and used in the promotion of private veterinary practice in Ghana.

PMID- 15449832
TI  - Perceptions of livestock owners of private veterinary practice in Ghana.
AB  - Using the participatory appraisal approach, a study was designed to assess the
      perceptions of livestock owners on private delivery of veterinary services in two
      districts in the major livestock-producing area in Ghana. A significant
      proportion (74%, n = 180) were willing to patronize locally established
      veterinary practices. However, the respondents emphasized that the fees charged
      had to be reasonable and affordable. Factors identified as likely to discourage
      the use of the private provider included the inability of the provider to speak
      the local language; non-availability of credit facilities for services rendered
      by the provider; unreliability of personnel; poor interpersonal skills; lack of
      technical know-how; inability of the provider to make house calls or farm visits;
      and poor personal and work ethics. These findings provide information for
      prospective private veterinarians on the expectations of their clients and could
      be used in the preparation of veterinarians for private practice.

PMID- 15449833
TI  - Observations on the clinical examination of the camel (Camelus dromedarius) in
      the field.
AB  - Camels usually inhabit remote areas, where diagnostic facilities and laboratories
      are very scarce. The species differences between the camel and other domestic
      animals necessitate some specific examination techniques. The objective of this
      study was to describe the clinical examination methods and sources of common
      errors that require special consideration in the camel. Young camels are examined
      in the standing position, while adults require restraint. Restraining procedures,
      both standing and in sternal recumbency, are described. New equipment and a crush
      were designed. The body temperature of the camels examined fluctuated from 35.7
      to 38.9 degrees C, being lowest in the morning and highest in the afternoon; high
      temperature in the morning is indicative of fever, while high afternoon
      temperatures could be hyperthermia. It was difficult to take the pulse rate for
      routine procedures. The heart rate ranged from 35 to 50 per min; there was no
      difference between the heart rate in the morning and in the afternoon. The mean
      respiratory rate was 11 per min and respiration was of thoracol-lumbar type. The
      mucous membranes of the eye were an important site for appreciating signs of
      discoloration, while those of the mouth, rectum and vagina were unsuitable. The
      left flank was the best site for determining the rate of rumen contractions,
      which was 3+/-1.2 every 5 min, as determined by auscultation; counting the
      contractions by the application of the fist was difficult. The palpable external
      lymph nodes were the parotid, maxillary, prescapular, inferior cervical,
      thoracic, cubital, ilial and popiteal; they are large and can be seen on
      inspection in healthy animals, so that was not indicative of disease. A list of
      diagnostic indicators for the rapid diagnosis of ten endemic camel diseases was
      generated from the empirical signs.

PMID- 15449834
TI  - Salmonella prevalence and distribution of serotypes in apparently healthy
      slaughtered camels (Camelus dromedarius) in Eastern Ethiopia.
AB  - The present study was undertaken to determine the prevalence and distribution of
      Salmonella from apparently healthy slaughtered camels in Eastern Ethiopia. A
      total of 714 samples (faeces, mesenteric, lymph nodes, spleen, liver, abdominal
      and diaphragmatic muscles) from 119 slaughtered camels were analysed. Salmonellae
      were detected from 116 (16.2%) of the 714 samples examined. Eighteen (15.1%)
      faeces, 19 (15.9%) mesenteric lymph nodes, 14 (11.8%) livers and 17 (14.3%)
      spleen samples (n = 119 for each) were positive for Salmonella. Salmonellae were
      found in 20.1% of the abdominal and diaphragmatic muscles. A total of sixteen
      different serotypes were identified of which Salmonella saintpaul (38.8%) and S.
      braenderup (22.4%) were the most prevalent followed by S. muenchen (8.6%), S.
      kottbus (6.0%) and S. havana (5.2%). Other serotypes, including S. typhimurium,
      S. heidelberg and S. enteritidis were also detected from Ethiopian camels.

PMID- 15449835
TI  - Pseudotuberculosis in dromedary camels in the Canary Islands.

PMID- 15449836
TI  - Risk factors for dairy cow mastitis in the central highlands of Ethiopia.
AB  - This study, with the objective of assessing the effect of risk factors on dairy
      cow mastitis in the central highlands of Ethiopia, was undertaken between
      February and September 2001 in the urban and peri-urban areas of Addis Ababa,
      Ethiopia. A prevalence study and questionnaire survey were carried out
      simultaneously. Clinical examination of lactating udders and California mastitis
      test (CMT) determined clinical and subclinical mastitis, respectively. Risk
      factors for subclinical and clinical mastitis were identified from data on
      animals and farm management by chi-square analysis and subsequent logistic
      regression. Cows aged at least 8 years, with poor body condition, with at least 8
      parities and in at least the eighth month of lactation had a significantly higher
      risk for subclinical mastitis (p < 0.05). The risk was reduced for cows up to
      their third parity in good body condition and for cows receiving dry cow therapy.
      Cows aged at least 4 years, or with at least 8 parities, cows in at least the
      fourth month of lactation, cows with poor body condition, leaking milk or
      previous udder infections had a significantly higher risk of clinical mastitis (p
      <0.05). The risk was reduced by the use of separate towels for udder cleaning and
      by drying off at the end of lactation. Most of the risk factors were in agreement
      with previous reports. However, stage of lactation and drying-off style were in
      contrast to others. Further research is needed to identify the interrelationship
      between production level, specific pathogens and management risk factors.

PMID- 15449837
TI  - Serum vitamin B12 levels in Omani goats.
AB  - Blood and faecal samples were studied from 200 Omani goats of both sexes and
      various age groups, within five different regions in Oman. Survey questionnaires
      were undertaken on each goat. The serum vitamin B12 values ranged from 105 to
      >2000 pg/ml, with a mean value of 723.1 pg/ml and a 95% confidence interval of 61
      1507 pg/ml. Kids in the age group 1-3 months showed significantly lower levels of
      serum vitamin B12 than the older animals. Varying levels of serum vitamin B12
      were found in different regions of Oman and on farms within the same region.
      Goats maintained on commercial feed showed higher levels of serum vitamin B12
      than those maintained on pasture or fed on household leftover food, as commonly
      practised in Oman. Coccidial counts were highest in animals with lower levels of
      serum vitamin B12. The results of this study indicate that there is a wide range
      of serum vitamin B12 levels in Omani goats and suggests that younger animals,
      with lower levels of serum vitamin B12, might be more susceptible to vitamin B12
      deficiencies than older animals.

PMID- 15449838
TI  - Fertility of Bunaji (zebu) cows after treatment with PRID with or without
      PGF2alpha.
AB  - A study was undertaken to determine the oestrus response and fertility rates of
      zebu cows treated with PRID alone or in combination with PGF2alpha. A total of
      184 non-suckled cycling Bunaji cows were allotted randomly to four treatment
      groups of 46 animals per group as follows: group 1 (PRID-12), PRID was inserted
      for 12 days; group 2 (PRID+7+PGF2alpha-6, PRID was inserted for 7 days and
      PGF2alpha was administered intramuscularly 1 day prior to PRID withdrawal; group
      3 (PRID-7+PGF2alpha-7, PRID was inserted for 7 days and PGF2alpha was
      administered intramuscularly on the day of PRID withdrawal; group 4 (2 x
      PGF2alpha-13, two intramuscular injections of PGF2alpha 13 days apart. At the end
      of each treatment period, the cows were observed for 7 days for behavioural
      oestrus and were inseminated 12 h following detection of oestrus. Pregnancy was
      diagnosed by rectal palpation 30-40 days post-insemination. The respective
      oestrus response rates were 78.3%, 76.1%, 87.0% and 89.1% for groups 1-4. While
      the corresponding pregnancy rates were 39.1%, 41.3%, 52.2% and 52.2%, the
      conception rates were 50.0%, 54.3%, 60.3% and 58.6% for groups 1-4. Although
      individual variations in progesterone levels were observed, the progesterone
      profiles were generally typical and normal. The results of the study have
      confirmed the effectiveness of the four regimes in synchronizing and controlling
      oestrus and ovulation in Bunaji cows. However, groups 3 and 4 showed some
      superiority over the other treatments. The results of this study provide feasible
      options from which clinicians involved in intensive breeding programmes and herd
      health fertility programmes can choose.

PMID- 15449839
TI  - Fertility of N'dama and Bunaji cattle to artificial insemination following
      oestrus synchronization with PRID and PGF2alpha in the hot humid zone of Nigeria.
AB  - A study was undertaken to determine the effectiveness of a progesterone-releasing
      intravaginal device (PRID) and prostaglandin F2 alpha (PGF2alpha) in
      synchronizing oestrus in N'dama and Bunaji cows and heifers and the fertility
      following artificial insemination at the synchronized oestrus. A total of 116
      cows and heifers (58 N'dama and 58 Bunaji) were used in two separate trials. In
      the first trial, oestrus was synchronized using a PRID, which was inserted for 12
      days; in the second trial, oestrus was synchronized by giving two injections of
      PGF2alpha 13 days apart. Only animals that did not respond to the first injection
      were given the second injection. At the end of each treatment period, the animals
      were observed for oestrus for 7 days and inseminated approximately 12 h following
      detection of oestrus. Standing to be mounted was the single criterion used to
      judge an animal to have been in oestrus. PGF2alpha and PRID were both effective
      in synchronizing oestrus in N'dama and Bunaji cows and heifers. The respective
      oestrus response rates, pregnancy rate and conception rates for PRID and
      PGF2alpha were 85.7%, 53.6% and 62.5% for PRID, and 91.7%, 68.3% and 74.6% for
      PGF2alpha. N'dama cattle showed significantly (p<0.05) better oestrus response
      rate, pregnancy rate and conception rate than Bunaji cattle following both PRID
      and PGF2alpha treatments. The pregnancy rate and conception rate following
      PGF2alpha treatment were better (p < 0.05) than for PRID, although the oestrus
      response rate did not differ. It is concluded that both PRID and PGF2alpha are
      effective in synchronizing oestrus in N'dama and Bunaji cattle in the hot humid
      zone of Nigeria and the fertility to artificial insemination at the synchronized
      oestrus was normal and acceptable. Thus, PRID and PGF2alpha can effectively be
      used in intensive breeding programmes for the rapid multiplication and
      distribution of both cattle breeds, especially the N'dama, which is a unique and
      beneficial animal genetic resource for the tsetse infested hot humid zone of
      Nigeria.

PMID- 15449840
TI  - Roasted full-fat kidney bean (Phaseolus vulgaris L.) and soyabeans (Glycine max)
      meals in broiler chicken diet.
AB  - An 8-week experiment was carried out to evaluate the performance of broiler
      chickens fed on diets containing either roasted full-fat soyabean meal (RSBM),
      roasted full-fat kidney bean meal (RKBM), cottonseed cake meal (CSM) or soyabean
      meal (SBM). A total of 240 unsexed, day-old-chicks were randomly assigned to four
      treatments so that there were 10 chicks per experimental unit in a randomized
      complete block design with three blocks and two replicates per block. Cumulative
      feed intake was depressed (p < 0.01) with the RSBM-based diet (71 g/bird per day)
      and was lowest with the RKBM-based diet (64 g/bird per day). Growth was closely
      related to feed intake, averaging 2122 g, 2094 g, 1960 g and 1601 g for CSM-, SBM
      , RSBM- and RKBM-based diets, respectively. However, feed conversion ratio (g
      food intake/g body weight gain) was similar at 8 weeks of birds' age, although
      the values were highest (p<0.01) at the first 2 weeks of age for birds fed on
      RKBM-based diets. Mortality was not affected (p >0.05) by treatment effects. Feed
      cost efficiency (CFA Franc (Fcfa) per kilogram live chicken) showed that the SBM
      based diet (494 Fcfa) and RKBM-based diet (493 Fcfa) were more expensive (p<0.01)
      than the RSBM-based diet (400 Fcfa). The CSM-based diet was the most economical
      (358 Fcfa) as a result of the lower market price of cottonseed cake. Despite
      suboptimal production performance and given current market prices, replacing
      imported SBM with locally produced RKBM, RSBM or CSM would allow farmers to save
      1%, 19% and 28%, respectively, on feed cost efficiency. Roasting soyabeans in
      place of imported SBM allowed farmers to save about 19% for each CFA franc spent
      on a kilogram of live bird at 8 weeks of age.

PMID- 15449841
TI  - An overview of sexually transmitted infections among adolescents.
AB  - Half of all United States high school students are sexually experienced. Female
      adolescents bear the highest rates of many STIs. Many adolescents infected with
      STIs report no symptoms suggestive of their infections. Health care providers who
      see adolescents should be poised to implement effective STI control through risk
      assessment, disease screening, and CDC-recommended treatment and prevention
      counseling.

PMID- 15449842
TI  - Sexually transmitted diseases in adolescents: biologic, cognitive, psychologic,
      behavioral, and social issues.
AB  - A large and complex array of risk and protective factors influence adolescents'
      sexual behavior and their risk for sexually transmitted diseases. Programs
      designed to reduce sexually transmitted diseases in adolescents should take a
      focused and integrated approach that addresses the modifiable biologic,
      cognitive, psychologic, behavioral, and social issues affecting adolescent sexual
      risk.

PMID- 15449843
TI  - Vaginitis in adolescents.
AB  - Vaginitis is a common complaint of adolescent females. It can cause extreme
      distress for some patients, especially those with recurrent symptoms. Thus, it is
      important to take care when evaluating these patients and to acknowledge their
      frustration when appropriate. A thoughtful and thorough history will determine
      most causes, with the most common being yeast, trichomoniasis, and BV.

PMID- 15449844
TI  - Urethritis and cervicitis in adolescents.
AB  - Sexually acquired lower-genitourinary tract infections are a significant source
      of morbidity for adolescents. Causative organisms include T. vaginalis,
      Mycoplasma organisms, Ureaplasma organisms, and, most commonly, N. gonorrhoeae
      and C. trachomatis. With NAATs, noninvasive screening can be accomplished easily.
      The importance of screening in high-risk populations cannot be overemphasized,
      especially because these infections are often asymptomatic. The treatment of
      sexually transmitted bacterial infections includes appropriate antibiotic
      treatment for the presenting patient, partner identification and treatment, and
      counseling to prevent reinfection.

PMID- 15449845
TI  - Pelvic inflammatory disease in adolescents.
AB  - Pelvic inflammatory disease (PID) is an infection of the upper female genital
      tract. It encompasses an array of inflammatory disorders, including endometritis,
      parametritis, salpingitis, oophoritis, tubo-ovarian abscess, peritonitis, and
      perihepatitis. In most adolescents with acute severe infections it is difficult
      to differentiate some of these entities; thus the term PID is used commonly.
      Perihepatitis (Fitz-Hugh-Curtis syndrome) and tubo-ovarian abscess are acute
      complications, whereas chronic complications include infertility, ectopic
      pregnancy, and chronic pain.

PMID- 15449846
TI  - Sexually transmitted disease testing: evaluation of diagnostic tests and methods.
AB  - Most STIs in adolescents are asymptomatic. Recent studies in adolescents have
      documented relatively short periods of time until reinfection occurs (median
      times 4.7-7.6 months), suggesting that sexually active adolescents should be
      screened for STI every 6 months. Evidence-based practice is exceedingly helpful
      in deciding when to test, whom to test, and which methodology to use. In a recent
      critical analysis regarding screening women for chlamydia, screening all women
      for chlamydia was more cost-effective than testing only symptomatic women. With
      the proliferation of highly sensitive and specific assays, and the usefulness of
      different specimen sources (such as urine or self-swabs), health care providers
      of adolescents should screen all patients at risk for STIs. Although these
      screening and diagnostic techniques provide greater accuracy than previously
      attainable, screening should be part of a comprehensive methodology designed to
      promote good health care decisions, such as encouraging abstinence, promoting
      safer sexual practices, and using the most appropriate methodology to detect and
      treat STIs.

PMID- 15449847
TI  - Human papillomavirus and cervical cytology in adolescents.
AB  - Human papillomavirus (HPV) infection is highly prevalent in adolescent girls and
      young women and may be associated with substantial morbidity and mortality. HPV
      infection may lead to condylomata (genital warts), cervical intraepithelial
      neoplasia (CIN), and cervical cancer. Recent research focused on the virology,
      natural history, and sequelae of HPV infection has led to evidence-based
      revisions of the system for classification of cervical cytology results,
      recommendations for cytologic screening, and guidelines for management of CIN.
      Vaccines to prevent HPV infection and its sequelae are under investigation.

PMID- 15449848
TI  - Sexually transmitted diseases causing genital lesions in adolescents.
AB  - Evaluating the adolescent with a genital lesion requires a thorough knowledge of
      the common and less-common STDs that cause genital findings. A thoughtful history
      and complete physical examination are always in order, as is testing for a
      particular suspected STD and for coexisting STDs, especially HIV.

PMID- 15449849
TI  - Lesbian, gay, bisexual, transgendered, and questioning youth: the importance of a
      sensitive and confidential sexual history in identifying the risk and
      implementing treatment for sexually transmitted infections.
AB  - STIs are one consequence of specific risk-taking behaviors, not sexual
      orientation. Providers who care for adolescents should be aware of the STIs for
      which LGBTQ youth are at risk and the necessary screening (see Table 1). Although
      it is vital to recognize that LGBTQ youth are at risk for STIs, it is important
      not to view the youth within this narrow perspective. LGBTQ youth, like all
      adolescents, should be appreciated for their individuality, idealism, and
      resiliency. Most LGBTQ youth emerge from adolescence as productive and healthy
      adults. Treating adolescents with understanding and respect and honoring
      confidentiality are integral to the physical and emotional health of young people
      dealing with sexual-identity issues. Understanding the process of sexual-identity
      formation is the first step in gaining knowledge and perspective about young
      people with sexual-identity issues and helping them reduce their risk for
      contracting STIs. Physicians caring for adolescents should consult recent
      comprehensive reviews to improve their understanding of the issues LGBTQ youth
      may encounter.

PMID- 15449850
TI  - HIV and AIDS in adolescents.
AB  - HIV infection in adolescents continues to challenge health providers,
      policymakers, and advocates for youth. There will be no relief from its
      complexities soon. Primary care providers are in a unique position to use
      effective HIV prevention and care interventions. Successful programs move beyond
      moralism to realism. They show a willingness to engage young people and their
      families in a sensitive dialogue about the needs of youthful sexual development.
      Youth at high risk for HIV should be identified and referred to comprehensive
      care and counseling as soon as possible. HIV-positive youth need intensive
      individual and group interventions to remain healthy and reduce transmission to
      others. To protect their patient population, health care providers will need to
      commit time and effort to making adolescents services visible, flexible,
      affordable, confidential, culturally appropriate, and universally available.

PMID- 15449851
TI  - New biomedical approaches for sexually transmitted infection prevention: vaccines
      and microbicides.
AB  - STIs are a major global health problem. Biomedical strategies are under
      development that will help prevent these infections. Vaccines against C.
      trachomatis and N. gonorrhoeae are in early stages of development. Stage-III
      trials are underway on prophylactic vaccines for HPV and HSV-2. Strategies
      focused on immunizing only high-risk individuals are unlikely to stem the tide of
      STIs. Approaches to widespread immunization require acceptance of such vaccines
      by health care providers, institutions providing funding, parents, and
      adolescents. Microbicides offer a female-controlled method for protection from
      STIs. They use many strategies to prevent infection. These products are at
      various stages of development. It seems that young women and teenagers would be
      interested in using microbicides. Correct and consistent use of microbicides will
      require taking women's preferences into account during product development and
      marketing.

PMID- 15449852
TI  - Sexually transmitted infections in adolescents: practical issues in the office
      setting.
AB  - The office-based clinician has an important role in preventing, diagnosing, and
      treating STIs in adolescents. Primary-care guidelines consistently recommend the
      annual screening of adolescents for sexual activity and its sequelae. Appropriate
      office-based care of adolescents requires a firm understanding of adolescent
      confidentiality laws as well as sensitivity to the adolescent's need for privacy.
      Counseling should be provided regarding abstinence, the use of condoms, and the
      value of dual contraception. Newer screening methods, such as the use of urine
      samples and nucleic-acid amplification techniques, may facilitate appropriate
      office-based screening for STIs in adolescent patients.

PMID- 15449853
TI  - Micromanager.
AB  - George Latour considers himself a good leader. As CEO of Retronics, George has a
      mandate to grow revenues with an eye toward taking the software-engineering firm
      public by 2006. At the behest of the chairman of the board, he has hired a new
      marketing director, Shelley Stern--"a thoroughbred" who, the chairman insists,
      just needs a little training in the business. George does his best to bring his
      new hire up to speed. He has Shelley sit in on developers' meetings, has her
      accompany the sales force on client calls, and even has the CFO explain the
      company's cash flow situation to her. He also takes pains to help her correctly
      position marketing and press materials. But Shelley never seems to really take
      the bit. In fact, Shelley considers George's hands-on management style
      oppressive, and she's dreadfully unhappy. What George sees as efforts to bring
      her up to speed, like making her go on those sales calls when she has other work
      to do, she views as signs that he doesn't trust her judgment. What's more,
      Shelley is spread too thin. Yet when she asks for help--if not additional staff,
      at least an outside contractor--George asks for a list of everything she's
      working on and tells her he'll help her prioritize. In this fictional case, a he
      said, she-said debate erupts over competing management styles. Four commentators-
      Jim Goodnight, the CEO of SAS Institute; Mark Goulston, a psychiatrist and the
      senior vice president at Sherwood Partners; J. Michael Lawrie, the CEO of Siebel
      Systems; and Craig Chappelow, the senior manager of assessment and development
      resources at the Center for Creative Leadership--offer their perspectives on the
      problem and how to solve it.

PMID- 15449854
TI  - New business with the new military.
AB  - A $200 billion market has appeared on your business horizon, but you may not have
      noticed it. It's the U.S. military--the new U.S. military. Virtually all aspects
      of the military are changing to ensure it can fight unpredictable threats while
      sustaining the infrastructure needed to support and train forces. The military is
      turning to non-traditional business partners to meet a wide range of needs, from
      health care to housing to information technology. The Defense Department is
      yielding its monopoly on every aspect of national security and adopting a more
      businesslike model in which the military's warfighting capabilities are supported
      through outsourcing and business alliances. Civilians are replacing military
      personnel in many noncombat roles. Military functions with corporate equivalents
      are candidates for outsourcing and privatization. Market standards are replacing
      the heavy customization that has locked many companies out of this marketplace.
      The authors have participated in the transformation process from different
      perspectives--one civilian, the other military. Together, they highlight the
      prospects that transformation is creating for companies outside the traditional
      defense industry and reveal paths to success in this complex market. They also
      present six principles for doing business with the military that require
      persistence, integrity, and a willingness to master the intricacies of a
      distinctive culture. By understanding the logic of military transformation,
      executives can identify and create vast new business opportunities. And by
      mastering the six principles, they can build profitable long-term relationships.

PMID- 15449855
TI  - Stop wasting valuable time.
AB  - Companies routinely squander their most precious resource--the time of their top
      executives. In the typical company, senior executives meet to discuss strategy
      for only three hours a month. And that time is poorly spent in diffuse
      discussions never even meant to result in any decision. The price of misused
      executive time is high. Delayed strategic decisions lead to overlooked waste and
      high costs, harmful cost reductions, missed new product and business development
      opportunities, and poor long-term investments. But a few deceptively simple
      changes in the way top management teams set agendas and structure team meetings
      can make an enormous difference in their effectiveness. Efficient companies use
      seven techniques to make the most of the time their top executives spend
      together. They keep strategy meetings separate from meetings focused on
      operations. They explore issues through written communications before they meet,
      so that meeting time is used solely for reaching decisions. In setting agendas,
      they rank the importance of each item according to its potential to create value
      for the company. They seek to get issues not only on, but also off, the agenda
      quickly, keeping to a clear implementation timetable. They make sure they have
      considered all viable alternatives before deciding a course of action. They use a
      common language and methodology for reaching decisions. And they insist that,
      once a decision is made, they stick to it--that there be no more debate or mere
      grudging compliance. Once leadership teams get the basics right, they can make
      more fundamental changes in the way they work together. Strategy making can be
      transformed from a series of fragmented and unproductive events into a
      streamlined, effective, and continuing management dialogue. In companies that
      have done this, management meetings aren't a necessary evil; they're a source of
      real competitive advantage.

PMID- 15449856
TI  - How global brands compete.
AB  - It's time to rethink global branding. More than two decades ago, Harvard Business
      School professor Theodore Levitt argued that corporations should grow by selling
      standardized products all over the world. But consumers in most countries had
      trouble relating to generic products, so executives instead strove for global
      scale on backstage activities such as production while customizing product
      features and selling techniques to local tastes. Such "glocal" strategies now
      rule marketing. Global branding has lost more luster recently because
      transnational companies have been under siege, with brands like Coca-Cola and
      Nike becoming lightning rods for antiglobalization protests. The instinctive
      reaction of most transnational companies has been to try to fly below the radar.
      But global brands can't escape notice. In fact, most transnational corporations
      don't realize that because of their power and pervasiveness, people view them
      differently than they do other firms. In a research project involving 3,300
      consumers in 41 countries, the authors found that most people choose one global
      brand over another because of differences in the brands'global qualities.
      Ratherthan ignore the global characteristics of their brands, firms must learn to
      manage those characteristics. That's critical, because future growth for most
      companies will likely come from foreign markets. Consumers base preferences on
      three dimensions of global brands--quality (signaled by a company's global
      stature); the cultural myths that brands author; and firms' efforts to address
      social problems. The authors also found that it didn't matter to consumers
      whether the brands they bought were American--a remarkable finding considering
      that the study was conducted when anti-American sentiment in many nations was on
      the rise.

PMID- 15449857
TI  - Why people follow the leader: the power of transference.
AB  - We all admire leaders. In trying to understand how leadership works, however, we
      often lose sight of the fact that followers are a crucial part of the equation.
      Regrettably, they get short shrift in the management literature, where they are
      described as merely responding to their leaders' charisma or caring attitudes.
      What most analyses seem to ignore is that followers have their own motivations
      and are as powerfully driven to follow as leaders are to lead. In this article,
      psychoanalyst, anthropologist, and management consultant Michael Maccoby delves
      into the unconscious recesses of followers' minds. He looks closely at the often
      irrational tendency to relate to a leader as some important person from the past-
      a parent, a sibling, a close friend, or even a nanny. Sigmund Freud discovered
      this dynamic when working with his patients and called it"transference." But as
      important as it is, the concept remains little understood outside the realm of
      clinical psychoanalysis. This is unfortunate, because a solid understanding of
      transference can yield great insight into organizational behavior and endow you
      with the wisdom and compassion to be a tremendous leader. The author explains the
      most common types of transference--paternal, maternal, and sibling--and shows how
      they play out in the workplace. He notes that they have evolved as our family
      structures have changed. Whether followers perceive a leader as an all-knowing
      father figure, as an authoritative yet unconditionally loving mother figure, or
      as a brother or sister who isn't necessarily a model of good behavior, the leader
      can manage transferential ties by bringing unconscious projections to light. Then
      debilitating resentment and animosity can give way to mutual understanding and
      productivity--and a limping organization can start to thrive.

PMID- 15449858
TI  - Deep smarts.
AB  - When a person sizes up a complex situation and rapidly comes to a decision that
      proves to be not just good but brilliant, you think, "That was smart." After you
      watch him do this a few times, you realize you're in the presence of something
      special. It's not raw brainpower, though that helps. It's not emotional
      intelligence, either, though that, too, is often involved. It's deep smarts. Deep
      smarts are not philosophical--they're not"wisdom" in that sense, but they're as
      close to wisdom as business gets. You see them in the manager who understands
      when and how to move into a new international market, in the executive who knows
      just what kind of talk to give when her organization is in crisis, in the
      technician who can track a product failure back to an interaction between
      independently produced elements. These are people whose knowledge would be hard
      to purchase on the open market. Their insight is based on know-how more than on
      know-what; it comprises a system view as well as expertise in individual areas.
      Because deep smarts are experienced based and often context specific, they can't
      be produced overnight or readily imported into an organization. It takes years
      for an individual to develop them--and no time at all for an organization to lose
      them when a valued veteran walks out the door. They can be taught, however, with
      the right techniques. Drawing on their forthcoming book Deep Smarts, Dorothy
      Leonard and Walter Swap say the best way to transfer such expertise to novices-
      and, on a larger scale, to make individual knowledge institutional--isn't through
      PowerPoint slides, a Web site of best practices, online training, project
      reports, or lectures. Rather, the sage needs to teach the neophyte individually
      how to draw wisdom from experience. Companies have to be willing to dedicate time
      and effort to such extensive training, but the investment more than pays for
      itself.

PMID- 15449859
TI  - Diversity as strategy.
AB  - IBM's turnaround in the last decade is an impressive and well-documented business
      story. But behind that success is a less told people story, which explains how
      the corporation dramatically altered its already diverse composition and created
      millions of dollars in new business. By the time Lou Gerstner took the helm in
      1993, IBM had a long history of progressive management when it came to civil
      rights and equal-opportunity employment. But Gerstner felt IBM wasn't taking full
      advantage of a diverse market for talent, nor was it maximizing the potential of
      its diverse customer and employee base. So in 1995, he launched a diversity task
      force initiative to uncover and understand differences among people within the
      organization and find ways to appeal to an even broader set of employees and
      customers. Gerstner established a task force for each of eight constituencies:
      Asians; blacks; the gay, lesbian, bisexual, transgendered community; Hispanics;
      white men; Native Americans; people with disabilities; and women. He asked the
      task forces to research four questions: What does your constituency need to feel
      welcome and valued at IBM? What can the corporation do, in partnership with your
      group, to maximize your constituency's productivity? What can the corporation do
      to influence your constituency's buying decisions so that IBM is seen as a
      preferred solution provider? And with which external organizations should IBM
      form relationships to better understand the needs of your constituency? The
      answers to these questions became the basis for IBM's diversity strategy. Thomas
      stresses that four factors are key to implementing any major change initiative:
      strong support from company leaders, an employee base that is fully engaged with
      the initiative, management practices that are integrated and aligned with the
      effort, and a strong and well-articulated business case for action. All four
      elements have helped IBM make diversity a key corporate strategy tied to real
      growth.

PMID- 15449860
TI  - Customer-centered brand management.
AB  - Most executives today agree that their efforts should be focused on growing the
      lifetime value of their customers. Yet few companies have come to terms with the
      implications of that idea for their marketing management. Oldsmobile, for
      example, enjoyed outstanding brand equity with many customers through the 1980s.
      But as the century wore further on, the people who loved the Olds got downright
      old. So why did General Motors spend so many years and so much money trying to
      reposition and refurbish the tired,tarnished brand? Why didn't GM managers
      instead move younger buyers along a path of less resistance, toward another of
      the brands in GM's stable--or even launch a wholly new brand geared to their
      tastes? Catering to new customers, even at the expense of the brand, would surely
      have been the path to profits. The reason, argue the authors, is that in large
      consumer-goods companies like General Motors, brands are the raison d'etre. They
      are the focus of decision making and the basis of accountability. But this
      overwhelming focus on growing brand equity is inconsistent with the goal of
      growing customer equity. Drawing on a wide range of current examples, the authors
      offer seven tactics that will put brands in the service of growing customer
      equity. These include replacing traditional brand managers with a new position-
      the customer segment manager; targeting brands to as narrow an audience as
      possible; developing the capability and the mind-set to hand off customers from
      one brand to another within the company; and changing the way brand equity is
      measured by basing calculations on individual, rather than average, customer
      data.

PMID- 15449861
TI  - Building deals on bedrock.
AB  - The headlines are filled with the sorry tales of companies like Vivendi and AOL
      Time Warner that tried to use mergers and acquisitions to grow big fast or
      transform fundamentally weak business models. But, drawing on extensive data and
      experience, the authors conclude that major deals make sense in only two
      circumstances: when they reinforce a company's existing basis of competition or
      when they help a company make the shift, as the industry's competitive base
      changes. In most stable industries, the authors contend, only one basis--superior
      cost position, brand power, consumer loyalty, real-asset advantage, or government
      protection--leads to industry leadership, and companies should do only those
      deals that bolster a strategy to capitalize on that competitive base. That's what
      Kellogg did when it acquired Keebler. Rather than bow to price pressures from
      lesser players, Kellogg sought to strengthen its existing basis of competition-
      its brand--through Keebler's innovative distribution system. A company coping
      with a changing industry should embark on a series of acquisitions (most likely
      coupled with divestitures) aimed at moving the firm to the new competitive basis.
      That's what Comcast did when changes in government regulations fundamentally
      altered the broadcast industry. In such cases, speed is essential, the
      investments required are huge, and half-measures can be worse than nothing at
      all. Still, the research shows, successful acquirers are not those that try to
      swallow a single, large, supposedly transformative deal but those that go to the
      M&A table often and take small bites. Deals can fuel growth--as long as they're
      anchored in the fundamental way money is made in your industry. Fail to
      understand that and no amount of integration planning will keep you and your
      shareholders from bearing the high cost of your mistakes.

PMID- 15449862
TI  - Doctor, doctor, gimme the news...preferably by e-mail.

PMID- 15449863
TI  - Identifying patient safety priorities.

PMID- 15449864
TI  - How to select the right consulting firm.

PMID- 15449865
TI  - Voice biometrics: just a whisper.

PMID- 15449866
TI  - On the road with mobile tech.

PMID- 15449867
TI  - Virtual technology offers real savings.

PMID- 15449868
TI  - Readers' perspectives... Vendors now offer clinical information systems that work
      well and complement the workflow of physicians and nurses.

PMID- 15449869
TI  - Diminished capacity: a guide to coping with America's packed hospitals.

PMID- 15449870
TI  - A narrowing door: hospitals, faced with ever-growing demand, may have to consider
      admission alternatives.

PMID- 15449871
TI  - Information=power. Modern Healthcare's third annual 100 Most Powerful ranking
      attests to the prominence of IT, quality and patient-safety initiatives.
AB  - The growing importance of IT is reflected in Modem Healthcare's third annual
      ranking of the 100 Most Powerful People in Healthcare. The person topping the
      2004 list is a newcomer who recently vaulted to prominence. Who is he, and what
      other industry movers and shakers made the ranking.

PMID- 15449872
TI  - Aim: supply chain gains. VHA cuts 125 positions in effort to refocus goals.

PMID- 15449873
TI  - Conflict crimps IT policy. HHS' rules called hindrance to technology.

PMID- 15449874
TI  - Another deal. LifePoint Hospitals grabs Province for $1.7 billion.

PMID- 15449875
TI  - Coming of age. Antitrust settlement between Fla. systems to expire.

PMID- 15449876
TI  - Making the best better.

PMID- 15449877
TI  - Surveying the damage. Hurricane Charley wreaks havoc on Fla. hospitals.

PMID- 15449878
TI  - On the rise IT leaders win recognition as the powerhouses in healthcare.

PMID- 15449879
TI  - Fix the broken DSH. CMS must step up to the plate to end fight over payment
      system.

PMID- 15449880
TI  - Certified and ready for duty. Fledgling healthcare IT commission to help
      determine what qualifies as a fully capable electronic medical-records system.

PMID- 15449881
TI  - Frivolous lawsuit, unmanageable debt.

PMID- 15449882
TI  - Was Joan of Arc criminally, responsible for her acts alleged of heresy?

PMID- 15449883
TI  - Parietal lobe strokes.

PMID- 15449884
TI  - Once upon a time, there was a little black bag.

PMID- 15449885
TI  - OutOfDate.

PMID- 15449886
TI  - Taking care and letting go.

PMID- 15449887
TI  - Don't let medicine lose its soul!

PMID- 15449888
TI  - Strangers, spirit, and fructose-2,6-bisphosphate.

PMID- 15449889
TI  - The secret society.

PMID- 15449890
TI  - Sister Mary Joseph and Mr. Hartdegin's cross to bear.

PMID- 15449892
TI  - Those great teachers from Kansas.

PMID- 15449893
TI  - A bipolar disorder: eurekaphoria, then discouragement.

PMID- 15449894
TI  - The nice approach to smokers.

PMID- 15449895
TI  - The author's craft? Or ingrained anti-Semitism?

PMID- 15449896
TI  - Dr. Solomon rejects the mantle of "the father of geriatrics".

PMID- 15449897
TI  - Yet another Eureka! Moment.

PMID- 15449898
TI  - [Toll-like receptors that sense viral infection].
AB  - Anti-viral host defense harbors a variety of strategies to coup with viral
      infection. Recent findings suggested that Toll-like receptors (TLRs) and their
      signaling pathways involve type I IFN induction in response to virus-specific
      molecular patterns. TLR 3 and TLR 4 in myeloid dendritic cells (mDCs) recognize
      viral dsRNA and putative viral products, respectively, to induce IFN-beta via IRF
      3 activation. On the other hand, TLR 7 and TLR 9 in plasmacytoid DCs (pDCs)
      induce IFN-alpha in response to their ligands, U/G-rich ssRNA and non-methylated
      CpG DNA. We identified TICAM-1 which is recruited to the cytoplasmic domain
      (designated TIR) of TLR 3 and allows to select the pathway to activation of IRF
      3. We also identified TICAM-2 which binds TLR 4 and together with TICAM-1
      activates IRF-3. TICAM-1 knockdown by RNAi supported the key role of TICAM-1 in
      IFN-beta induction. Hence, the IFN-beta induction in mDCs appears in part due to
      the function of TICAM-1. Viruses are known to activate kinases that directly
      activate IRF-3 inside the cells, and this pathway may merge with the TLR 3-TICAM
      1 pathway. Here we review the relationship between the TLR 3-TICAM-1 pathway and
      viral infection.

PMID- 15449899
TI  - [Lipid raft and influenza virus--viral glycoproteins on a raft].
AB  - Lipid molecules of the plasma membrane are not distributed homogeneously, but
      form a lateral organization resulting from preferential packaging of sphingolipid
      and cholesterol into lipid microdomain rafts, in which specific membrane proteins
      become incorporated. Evidence has accumulated that a variety of viruses including
      influenza virus use the raft during some steps of their replication cycles.
      Influenza virus glycoproteins, hemagglutinin (HA) and neuraminidase, associate
      intrinsically with the rafts. The HA protein is distributed in clusters at the
      plasma membrane and concentrated in the small area by interacting with the raft.
      A mutant influenza virus, whose HA protein lacks the ability to associate with
      the raft, contains reduced amounts of the HA proteins and exhibits a decreased
      virus to cell fusion activity, resulting in greatly reduced infectivity. Thus,
      the raft may play an important role in virus production by acting as a
      concentrating devise or an efficient carrier to transport the HA protein to the
      site of virus budding.

PMID- 15449900
TI  - [Zoonoses].
AB  - The numbers of microbial species that can infect human beings are shown to be
      1415, of which 868 species (61%) are zoonotic. Since most of the emerging
      pathogens (75%) are originated from other animals, public health sectors should
      be vigilant against the emergence of new zoonotic diseases. Only 33% of zoonoses
      can spread from human to human after introduction into human population. Various
      factors such as human demography, ecological change, global transportation and
      climate change are responsible for the emergence of zoonoses. Even a slight
      change in the ecological niche where pathogenic organisms thrive would result in
      the increase of the incidence of the disease.

PMID- 15449901
TI  - [Transcriptome analysis of virus-infected cells].
AB  - Human genome project revealed that human genes are derived from 30,000-40,000
      species of genetic loci, which had been estimated as approximately 100,000. The
      project also promoted devising novel tools that enable us to analyze biological
      phenomena comprehensively. Microarray technology is a representative of the novel
      tools in genomics and engages us to explore genome-wide expression levels of
      genes simultaneously (transcriptome analysis). Here we show transcriptomes
      obtained from 10 species of cells infected with human cytomegalovirus, as a model
      virus, by a synthetic DNA microarray system that we have established recently.
      Our system provides simultaneous and parallel description on alteration of
      expression of viral and host genes that are represented within a single area on a
      slide glass. Moreover, we propose a project entitled 'comparative virology on
      cellular responses of infected hosts' that consists of multiple acquisition and
      integration of transcriptomes from a combination of several cells and viruses as
      a panel on the identical platform. The attempt should extract a novel concept in
      virology from investigation on differences and similarities among influence of a
      virus on a variety of different cells and conversely among responses of a species
      of cells against a variety of different viruses.

PMID- 15449902
TI  - [Sequence variation of HIV and bioinformatics].
AB  - The envelope glycoprotein of human immunodeficiency virus type 1 (HIV-1)
      interacts with receptors on the target cell and mediates virus entry by fusing
      the viral and cell membranes. To maintain the viral infectivity, amino acids that
      interact with receptors are expected to be more conserved than the other sites on
      the protein surface. In contrast to the functional constraint of amino acids for
      the receptor binding, some amino acid changes in this protein may produce
      antigenic variations that enable the virus to escape from recognition of the host
      immune system. Therefore, both positive selection (higher fitness) and negative
      selection (lower fitness) against amino acid changes are taking place during
      evolution of surface proteins of parasites To elucidate the evolutionary
      mechanisms of the whole HIV-1 gp120 envelope glycoprotein at the single site
      level, we collected and analyzed all available sequence data for the protein. By
      analyzing 186 sequences of the HIV-1 gp120 (subtype B), we reevaluated amino acid
      variability at the single site level, and estimated the numbers of synonymous and
      nonsynonymous substitutions at each codon position to detect positive and
      negative selection. We identified 33 amino acid positions which may be under
      positive selection. Some of these positions may form discontinuous epitopes. We
      also analyzed amino acid sequences to find amino acid positions responsible for
      usage of the second receptor. We found that, in addition to the V3 loop, amino
      acid variation at residue 440 in C4 region is clearly linked with the usage of
      CXCR 4.

PMID- 15449903
TI  - [Structural biology of human CD81, a receptor for hepatitis C virus].
AB  - Human CD81, which is belonged to tetraspanin family, has been previously
      identified as a receptor for the hepatitis C virus envelope E 2 glycoprotein. The
      crystal structure of the human CD81 long extracellular domain, binding site for E
      2 glycoprotein, is presented here at 1.6 A resolution. The tertiary structure of
      CD81-LEL, which is composed of five alpha-helices, is resemble for a mushroom
      shaped molecules (stalk and head subdomains) and forms a dimer in the
      crystallographic asymmetric unit. The two disulfide bridges, which are conserved
      all the tetraspanin and are necessary for CD 81-HCV interaction, are stabilizing
      the conformation of the head domain. This head domain is solvent exposed surface
      region and is locating the amino acid residues which are essential for the E 2
      binding. The hydrophobic cluster in this head domain may suggest that the
      presence of a docking site for a low complementary surface cavity in the partner
      E 2 glycoprotein. We proposed that the dimer structure may be important in the
      interactions of HCV E 2 glycoprotein and also the viral protein may occur in
      dimeric aggregation on the HCV envelope. This common structural motif of the
      tetraspanin provides the first insight onto the mechanism of HCV binding to human
      cell and may be targets for structure-based antiviral drug.

PMID- 15449904
TI  - [Development and application of gene therapy technologies].
AB  - The success of hematopoietic stem cell gene therapy for X-linked severe combined
      immunodeficiency (X-SCID) was a major breakthrough in the field of gene therapy.
      However, two patients treated with this gene therapy developed leukemia at a
      later time, and retroviral vector-mediated gene transfer was considered to
      trigger leukemogenesis; i.e. insertional mutagenesis caused activation of LMO 2
      gene, which was one step toward leukemia development. To cope with this serious
      problem, basic studies are required to improve the safety of retroviral vectors
      and to develop the method for site-specific integration of transgenes. In
      addition, we have to develop technologies such as selective amplifier genes
      (SAGs), the system for selective expansion of transduced cells, in order to
      obtain therapeutic efficacy of hematopoietic stem cell gene therapy in many other
      disorders. Moreover, clinical applications of AAV vector are promising from the
      standpoint of safety issue, because this vector is derived from non-pathogenic
      virus. AAV vector is appropriate for gene transfer into neurons, muscles, and
      hepatocytes. For example, gene therapy for Parkinson's disease is investigated
      using AAV vectors. Genetic manipulation is also one of the indispensable
      technologies in the field of regeneration medicine, and further promotion of
      basic research is important.

PMID- 15449905
TI  - [Recent progress in anti-HIM-1 research].
AB  - Establishment of highly active antiretroviral therapy (HAART) has brought about
      dramatic improvement of the prognosis of HIV-1 infection. On the other hand,
      several drawbacks associated with long-term HARRT have been demonstrated. Among
      them, emergence of drug-resistant viruses is a serious problem; therefore
      compounds with novel mechanisms of action have been investigated to overcome the
      problem. Novel reverse transcriptase inhibitors (RTIs) and protease inhibitors
      (PIs) recently approved for clinical use are effective against existing resistant
      strains by once daily administration. In addition, the virus entry (fusion)
      inhibitor has also been licensed. Since this compound targets a molecule other
      than reverse transcriptase and protease for inhibition of HIV-1 replication, it
      is active against HIV-1 highly resistant to RTIs and PIs. Furthermore, clinical
      trials with CCR 5 (coreceptor of HIV-1) antagonists are in progress, and
      inhibitors of integrase, HIV-1 gene expression, and virion assembly have been
      identified.

PMID- 15449906
TI  - [Anti-tumor immunity in adult T-cell leukemia].
AB  - Adult T-cell leukemia (ATL) occurs in a small population of human T-cell leukemia
      virus type I (HTLV-I)-infected individuals. It has been noted that ATL is
      incidentally associated with mother-to-child infection which occurs mainly
      through breast-feeding, elevated levels of proviral load, and insufficiency in
      HTLV-I-specific cytotoxic T lymphocyte (CTL) responses. Among these, anti-tumor
      potentials of HTLV-I-specific CTL have been shown in ex vivo analysis of human
      HTLV-I-infected individuals and also in vivo experiments by using rat models of
      HTLV-I-infected lymphomas. In another rat model of HTLV-I-infection, orally
      infected rats showed significantly higher HTLV-I proviral load but lower HTLV-I
      specific cellular immune responses than in intraperitoneally infected rats. As a
      result, persistent viral load was inversely correlated with levels of virus
      specific T-cell responses. HTLV-I-specific T-cell responses in orally infected
      rats recovered by re-immunization. Conversion of Tax-specific T-cell responses
      from low to high levels was also observed in an ATL patient who obtained complete
      remission after hematopoietic stem cell transplantation. These findings suggest
      that HTLV-I-specific immune unresponsiveness associated with oral HTLV-I
      infection may be a potential risk factor for development of ATL, allowing
      expansion of the infected cell reservoir in vivo, and that immunological
      strategies targeting Tax may potentially reduce the risk of ATL and induce
      therapeutic effects on ATL.

PMID- 15449907
TI  - [Studies on virulence of HIV and development of non-virulent live AIDS vaccine
      using monkeys].
AB  - A great effort for developing AIDS vaccine has been carried out in the world,
      designed by various new ideas based on basic research information obtained in
      recent virology and immunology. Withall it, to obtain effective AIDS vaccine is
      considered skeptical. One of the reasons of its difficulty is a lack of
      experimental animals susceptible to HIV-1. In our laboratory, we have succeeded
      in developing chimeric SIV having 3' half of HIV-1 genome including env (SHIV),
      which is infectious to macaque monkeys. One of SHIVs has been proved
      nonpathogenic in monkeys from various aspects and it afforded protective immunity
      to monkeys against pathogenic SHIV challenge infection. Now, we are trying to
      develop anti-HIV live attenuated vaccines using the nonpathogenic SHIV as a
      starting material. In the history of virus vaccine, live attenuated vaccines have
      been proved most effective in measles and polio-myelitis. However, it is not
      clear whether nonpathogenic HIV exists or not. Futhermore, even if nonpathogenic
      HIV could be obtained, there is possibility that it will easily mutate to
      pathogenic one. Therefore, to develop live attenuated AIDS vaccine is considered
      dangerous. In this article, We will introduce our research on SHIV pathogenicity
      using monkeys and hypothesize possibility to obtain nonpathogenic HIV which is
      speculated from the origin and evolution of HIV/SIV. To clarify virulence and
      nonvirulence of HIV and to obtain nonpathogenic virus are not only applied
      research but also basic science to dissolve the fundemental question why HIV can
      induce the disease.

PMID- 15449908
TI  - [Novel function of plasminogen-binding activity of the NA determines the
      pathogenicity of influenza A virus].
AB  - Because cleavage of the hemagglutinin (HA) molecule by proteases is a
      prerequisite for infectivity of influenza A viruses, this molecule is a major
      determinant of viral pathogenicity. Although well documented in the pathogenicity
      of avian influenza viruses, the role of HA cleavage in the pathogenicity of
      mammalian viruses is not well understood. Therefore, we studied a mouse-adapted
      human isolate A/WSN/33 (WSN), a neurovirulent influenza virus strain that causes
      systemic infection when inoculated intranasally into mice. We found a novel
      mechanism of HA cleavage for WSN virus: the neuraminidase (NA) of WSN virus binds
      and sequesters plasminogen on the cell surface, leading to enhanced cleavage of
      the HA. The structural basis of this novel function of the NA molecule appears to
      be the presence of a carboxyl-terminal lysine and the absence of an
      oligosaccharide side chain at position 146. To obtain direct evidence that the
      plasminogen-binding activity of the NA enhances the pathogenicity of WSN virus,
      we generated mutant viruses that are deficient in plasminogen-binding activity by
      reverse genetics. The mutant viruses showed attenuated growth in mice and failed
      to grow at all in the brains of these animals. Therefore, we concluded that the
      novel function of plasminogen-binding activity of the NA determines the
      pathogenicity of WSN virus in mice.

PMID- 15449909
TI  - [Avian influenza virus].
AB  - Recent outbreaks of highly pathogenic avian influenza in chickens and ducks that
      occurred in 9 Asian countries including Japan alarmed to realize that there is no
      border for infections and gave a rise to great concern for human health as well
      as for agriculture. This H5N1 virus jumped the species barrier and caused severe
      disease with high mortality in humans in Viet Nam and Thailand; 15 deaths of 22
      cases and 8 of 12, respectively. A second concern was the possibility that the
      situation could give rise to another influenza pandemic in humans since genetic
      reassortment may occur between avian and human influenza viruses when a person is
      concurrently infected with viruses from both species. This process of gene
      swapping inside the human body can give rise to a new subtype of the influenza
      virus to which humans would not have immunity. The outbreaks also emphasized the
      need to continue active surveillance on avian influenza throughout the year to
      undertake aggressive emergency control measures as soon as an infection is
      detected.

PMID- 15449910
TI  - [Current topics on SARS coronavirus].
AB  - The serious respiratory disease, SARS (Severe Acute Respiratory Syndrome),
      outbreaking in winter of 2003 to 2004 remained in a sporadic patient's generating
      at this winter. However, there is also a possibility that wild animals as the
      source of infection may not be specified and that it may be much in fashion
      again. The paper regarding SARS and SARS-CoV is published at one per day now
      which has passed since fashion of SARS in one or so year. There are many papers
      which the researchers of other viruses enter into the research field of SARS-CoV
      using their own technology in addition to the researchers of coronavirus. Topics
      of the research on the present SARS-research field are development of vaccine,
      inspecting of medicine and establishment of diagnostic method. Here, the newest
      information is offered about these researches.

PMID- 15449911
TI  - [Principle of LAMP method--a simple and rapid gene amplification method].
AB  - So far nucleic acid test (NAT) has been employed in various fields, including
      infectious disease diagnoses. However, due to its complicated procedures and
      relatively high cost, it has not been widely utilized in many actual diagnostic
      applications. We have therefore developed a simple and rapid gene amplification
      technology, Loop-mediated Isothermal Amplification (LAMP) method, which has shown
      prominent results of surpassing the performance of the conventional gene
      amplification methods. LAMP method acquires three main features: (1) all reaction
      can be carried out under isothermal conditions; (2) the amplification efficiency
      is extremely high and tremendous amount of amplification products can be
      obtained; and (3) the reaction is highly specific. Furthermore, developed from
      the standard LAMP method, a rapid LAMP method, by adding in the loop primers, can
      reduce the amplification time from the previous 1 hour to less than 30 minutes.
      Enormous amount of white precipitate of magnesium pyrophosphate is produced as a
      by-product of the amplification, therefore, direct visual detection is possible
      without using any reaction indicators and detection equipments. We believe LAMP
      technology, with the integration of these features, can rightly apply to clinical
      genetic testing, food and environmental analysis, as well as NAT in different
      fields.

PMID- 15449912
TI  - [Round table discussion on highly pathogenic H5N1 avian influenza].

PMID- 15449913
TI  - Campylobacter and emerging antimicrobial resistance.

PMID- 15449914
TI  - Cancer esophagus Karachi 1995-2002: epidemiology, risk factors and trends.
AB  - OBJECTIVE: To study the trends of cancer esophagus in Karachi South during 1995
      2002 and identify risk factors. METHODS: Incident esophageal cancer cases
      recorded at the Karachi Cancer Registry for Karachi South, during 1st January
      1995 to 31st December 2003 were reviewed. For maximum completion of data,
      incident cases registered from 1st January 1995 to 31st December 2002 were
      included for final analyses. RESULTS: The Age Standardized Incidence Rates
      (ASIRs) of cancer esophagus in Karachi South for males were 6.5/100,000 (1995
      1997) and 6.4/100,000 (1998-2002). In females the observed rates were 7.0/100,000
      (1995-1997) and 8.6/100,000 (1998-2002). CONCLUSION: In the moderately high
      incidence, cancer esophagus zone of Karachi, the ASIRs in males remained stable
      during the last decade, but in females, an upward trend was observed suggesting a
      progressively higher exposure to risk factors in the latter. The potential risk
      factors in Karachi are use of all forms of tobacco, areca nut, infrequent
      consumption of raw fruits and vegetables and diet deficiencies. There is a
      necessity to actively control the proven risk factors and address the existence
      of other risk factors. The primary recommended strategy for the control of cancer
      esophagus would therefore be legislation against tobacco and areca nut in
      Pakistan and public health education. The risk factors of cancer esophagus
      identified in this article need to be further confirmed.

PMID- 15449915
TI  - Value of D-dimers assay in diagnosis of pulmonary embolism.
AB  - OBJECTIVE: To determine the value of D-Dimers assay in the diagnosis of Pulmonary
      Embolism (PE) at Armed Forces Institute of Pathology, Rawalpindi, Pakistan from
      January to November 2000. METHODS: Forty three consecutive patients clinically
      suspected of suffering from pulmonary embolism and referred to Armed Forces
      Institute of Pathology for Ventilation-Perfusion scan of lungs were inducted in
      the study. A detailed history was taken and clinical examination was performed.
      All patients were then subjected to Perfusion and/or Ventilation scan, which was
      taken as the standard for the diagnosis of PE. Blood samples were collected from
      all patients in trisodium citrate. Platelet poor plasma obtained from the samples
      was tested for D-Dimers semi-quantitatively using latex agglutination method.
      RESULTS: Out of 43 patients 14 (32.6%) had completely normal ventilation
      perfusion scan hence the diagnosis of PE was excluded. In 6 (13.9%) patients the
      results were considered indeterminate. Abnormalities suggestive of pulmonary
      embolism were detected in 23 (53.5%) patients. D-Dimers were less than the cut
      off value of 500 ng/ml in 19 (44.2%) patients, whereas in 24 (55.8%) the levels
      were more than 500 ng/ml. When compared with the results of ventilation-perfusion
      scan the sensitivity of D-Dimers was 91.3% and specificity was 100%. Positive
      predictive value of the test was 100% whereas negative predictive value was
      87.5%. CONCLUSION: D-Dimers assay combined with high clinical evidence is a cost
      effective, readily available test which can safely exclude the diagnosis of
      pulmonary embolism in majority of the cases.

PMID- 15449916
TI  - Patient controlled intravenous analgesia (PCIA) in postoperative surgical
      patients: an audit.
AB  - OBJECTIVE: We conducted an audit for the evaluation of the effectiveness, adverse
      effects and degree of patient satisfaction with Patient Controlled Intravenous
      Analgesia (PCIA) for postoperative pain control in surgical patients. METHOD:
      This was an observational study. Patient, scheduled for different surgical
      procedures, were informed about PCIA a day before surgery and were offered PCIA
      for pain control after surgery. All the patients were asked to fill a
      questionnaire 24 hours after the start of PCIA, that contained the relevant
      questions reflecting the objectives of the study. RESULTS: Seventy-six patients
      participated in the study of whom 91% had a visual analogue pain score of <3 at
      rest and 83% had a score of <3 at movement on visual analogue scale of 0-10.
      Eighty percent of patients rated the convenience of pain control as being
      excellent, whereas 92% stated that the dependence on nursing staff for pain
      management was nil. The incidence of drowsiness and nausea was 28% each, while
      21% of the patients complained of restricted mobility. CONCLUSION: Patient
      controlled intravenous analgesia is an excellent method of postoperative pain
      relief, which provides a high degree of satisfaction to the patients.

PMID- 15449917
TI  - Emerging bacterial resistance patterns in febrile neutropenic patients:
      experience at a tertiary care hospital in Pakistan.
AB  - OBJECTIVE: To look at the clinical presentations, spectrum and site of isolation
      of the organisms, sensitivity patterns of the organisms and the antibiotic
      prescribing practices for the treatment of febrile neutropenic patients at our
      hospital. METHODS: The data were collected retrospectively from the records of
      all neutropenic patients with an absolute neutrophil count (ANC) of less than
      500/ml admitted during the period of 3 years from August 1999 to July 2002 at
      AKUH. RESULTS: Out of the total of 404 patients, 65% had hematological
      malignancies and around half of them had leukaemia, 86% of the patients presented
      with fever. A total of 124 bacterial organisms were isolated from 96 patients
      among which 47% were gram positive and 53% were gram negative organisms; 16.1% of
      the patients had septicaemia. Coagulase Negative Staphylococci (CoNS) were the
      most common gram positive and E. coli was the most commonly isolated gram
      negative organism. Most of the gram positive organisms were isolated from blood
      (67%). There was emerging resistance to all commonly used antibiotics including
      imipenem, cloxacillin, vancomycin and amikacin. The average duration of
      neutropenia was 6.4 days. The mortality rate was 6%. CONCLUSION: There is
      increasing trend of gram negative organisms developing resistance to commonly
      used antibiotics. Gram positive bacteria including Enterococcus spp. and CoNS are
      also showing emerging resistance to vancomycin.

PMID- 15449918
TI  - Effects of depth of incision on final outcome in radial keratotomy.
AB  - OBJECTIVE: To assess the effect of depth of incision on the final outcome of
      radial keratotomy for correction of myopia. METHODS: Sixty-five eyes with
      preoperative uncorrected myopia between 2.5-6.0D in subjects with a mean age of
      29.2 (+/-7) years underwent radial keratotomy between Sept 1999-July 2002 in
      department of Ophthalmology, Military Hospital, Rawalpindi. Based on their
      preoperative depth of incision the eyes were divided into group-A (twenty-five
      eyes), with an incision depth of 500-530 microm, and Group-B (forty eyes), with
      an incision depth of 531-560 microm. The comparison between the postoperative
      visual acuity of two groups was made at the end of study after one years' follow
      up. RESULTS: A total of Sixteen eyes in Group-A (64%) that were within one
      diopter of emmetropia at first follow-up reverted back to their preoperative
      myopic state after one year of surgery as compared to only two eyes (5%) in Group
      B (p<0.05). Hyperopic shift occurred in two eyes (8%) in Group-A, as compared to
      four eyes (10%) of Group-B (p>0.05). After one year, refraction showed that only
      24% cases of Group-A were within 1 diopter of emmetropia as compared to 85% cases
      in Group-B. Similarly, 40% cases of Group-A were within 2 diopters of emmetropia
      as compared to 90% cases of Group-B. Glare and variation of vision in the initial
      four weeks were the most frequently reported complications in both groups.
      CONCLUSION: Depth of corneal incision significantly affects the outcome of
      surgery, if central optical zone is kept the same in cases of low to moderate
      degrees of myopia.

PMID- 15449919
TI  - Evaluation and comparison of coronary heart disease risk factor profiles of
      children in a country with developing economy.
AB  - OBJECTIVE: To define the risk factors (RF) profile and prevalence rates of high
      risk factors in an urban Pakistani community and compare it to the RF profile and
      prevalence rates of Pakistan National Health Survey. METHODS: The present study
      included RF relevant data of 400 house hold children selected by open invitation
      as a part of Metroville Health Study (MHS), a risk factor modification study
      which was a cooperation between National Heart Lung Blood institute (NHLBI) USA
      and National Institute of Cardiovascular Diseases Pakistan. The base line data of
      389 girls and 417 boys age 5-17 was included. PMRC data of 5067 and NHANES III
      survey data of 10,252 US children was used for comparison with MHS. RF analyzed
      were height weight, SBP, DBP, BMI and serum cholesterol. Comparisons between MHS
      and PMRC and US were made by using two tailed student t test and of high RF were
      defined as those exceeding US standards and expressed as percentages. RESULTS:
      The RF factor profile of urban Metroville children was worse than the national
      average of PMRC children. Except for diastolic blood pressure in both boys and
      girls and SBP in PMRC boys, all other RF were less than US children. Prevalence
      rates were higher in urban Metroville community, i.e., MHS compared to the PMRC
      which represents national average data. CONCLUSION: RF profile of Pakistani
      children has been presented and effect of urbanization demonstrated by comparing
      the PMRC and MHS RF profile. Hypertension in Pakistani children has emerged as a
      single most important RF requiring urgent prevention.

PMID- 15449920
TI  - Radiocontrast nephropathy: is it dose related or not?
AB  - OBJECTIVE: To assess the safety of high dose non-ionic contrast media during a
      single radiological procedure in patients with pre-existing renal impairment.
      METHODS: One hundred eighteen patients, with serum Creatinine greater than 1.3
      mg/dl who were undergoing coronary angiography or percutaneous transluminal
      coronary angiography (PTCA) were included in the study. All patients received the
      nonionic dye ULTRAVIST (lopromide). Serum creatinine were measured before, 48
      hours and 1 week after the administration of contrast agent. An acute contrast
      induced reduction in renal function was defined as an increase in Serum
      Creatinine concentration of >=0.5 mg/dl, 48 hours after the administration of
      contrast agent. All patients with end stage renal disease or patients undergoing
      coronary bypass surgery within a week after coronary angiography or had any
      concomitant factors that could cause acute renal failure e.g., sepsis,
      hypotention, etc., were excluded. Patients receiving a dose of upto 100 ml of
      contrast agent (low dose group) were separated from those who received greater
      than 100 ml of contrast agent (high dose group). Patients in both groups had
      similar characteristics in terms of sex, age, weight and underlying disease.
      Student's t-test was used for statistical analysis. RESULTS: The mean age of our
      patients was 62.3+/-8.83 (range 40-84 years). There were 93 (78.8%) males and 25
      (21.2%) females. The mean pre-contrast creatinine in the low contrast group was
      1.97+/-0.92 and high dose group was 2.16+/-1.90 (p=0.48). The post-contrast
      Creatinine at 48 hours was 2.11+/-1.11 and 2.06+/-1.39 in the groups receiving
      low and high dose contrast agents respectively (p=0.830), while at 7 days post
      contrast it was 2.17+/-1.28 and 1.95+/-1.43 respectively in the two groups
      (p=0.391). The contrast-induced reduction in renal function (rise in serum Cr
      >=0.5 mg/dl above base line) occurred in 14% (n=8) of patients in low dose and in
      11% (n=7) in high dose contrast group (p=0.830, insignificant). CONCLUSION: The
      results of our study confirm that high dose non-ionic contrast is not associated
      with increased risk of contrast-mediated nephrotoxicity in patients with pre
      existing renal insufficiency undergoing cardiac angiography (p=0.830,
      insignificant).

PMID- 15449921
TI  - Low cost quality control human serum: method of preparation, validation of values
      and its comparison with the commercial control serum.
AB  - OBJECTIVE: To prepare low-cost quality controls (QC) human serum and
      scientifically evaluate its advantages/disadvantages when compared with
      commercially available sera. METHODS: The home made QC serum was prepared as per
      WHO recommended protocol from four healthy volunteers. It was screened for HIV,
      HCV and HBV, pooled together and stabilized with ethylene glycol. The initial 40
      values were used for calculation of means, SDs and CVs for seventeen routinely
      measured analytes and results were compared with those of commercially available
      lyophilized human sera. RESULTS: The average concentrations of seventeen commonly
      analyzed constituents were found to be near the middle of the physiological range
      of healthy subjects and the home made serum could be a good substitute for the
      commercial serum of normal range. The narrower CVs of the analytes imply a lesser
      vial to vial variation in the home made sera. Additional advantages include easy
      preparation, no need for reconstitution and lower cost. CONCLUSION: Home made
      serum is a good substitute for the commercial serum of the normal range
      especially in developing countries like Pakistan.

PMID- 15449922
TI  - Rapid detection of rifampicin susceptibility of Mycobacterium tuberculosis in
      sputum specimens by mycobacteriophage assay.
AB  - OBJECTIVE: To evaluate the performance of FASTPlaqueTB-RIF, a newly introduced
      bacteriophage assay for rapid detection of rifampicin susceptibility of
      Mycobacterium tuberculosis in sputum specimens. METHODS: A comparative study of
      40 sputum specimens from patients of pulmonary tuberculosis, using FASTPlaqueTB
      RIF and Bactec 460 TB system carried out at the Armed Forces Institute of
      Pathology, Rawalpindi between September and November 2001. RESULTS: Of the 40
      clinical isolates of Mycobacterium tuberculosis tested for rifampicin (RIF)
      susceptibility using the Bactec 460 TB system, 28 isolates were resistant to RIF
      and 12 isolates were susceptible. FASTPlaqueTB-RIF identified 24 specimens as
      resistant to RIF. Three specimens that revealed susceptible isolates on Bactec
      460, were resistant by FASTPlaqueTB-RIF while four specimens which revealed
      resistant isolates on Bactec 460, demonstrated susceptibility to RIF by
      FASTPlaqueTB-RIF. The sensitivity and specificity of FASTPlaqueTB-RIF were 86%
      and 73% respectively. The predictive values of positive and negative tests were
      0.89 and 0.67 respectively. The overall accuracy of the technique was 82%. The
      phage assay took 48 hours to perform. CONCLUSION: Early detection of rifampicin
      resistance by the mycobacteriophage technique direct from sputum specimens is a
      potentially useful new test which would allow decision regarding appropriate
      therapy to be made early thus having a positive impact on patient care and on
      prevention of spread of MDR TB.

PMID- 15449923
TI  - Socioeconomic differences in housewife's ability to take nutritional care.
AB  - OBJECTIVE: To explore socio-economic differences in 'Nutritional Care Potential'
      (NCP) of housewives belonging to three distinctively different income groups
      living in urban areas of Karachi. METHODS: Data was collected from families
      living in small, medium and large sized houses located in the authorized urban
      residential areas of Karachi. A total of 180 housewives (60 each for low, middle
      and high income groups) were interviewed. Trained data collectors visited the
      households, interviewed the housewives about family's socio-demographic
      characteristics and their own nutritional knowledge, health locus of control and
      decision making. RESULTS: The total NCP scores increased with income level (Low =
      14.8+/-5.6; Middle 16.58+/-5.5; High = 17.28+/-5.3) but the difference was
      statistically significant only between low and high income groups (t-test P =
      0.015). The mean nutrition knowledge score of low income group was lower (mean
      score = 11.7+/-4.1) and significantly different from both middle (mean score =
      13.5+/-3.4 t-test P = 0.013) and high income group (mean score = 14.2+/-4.0, t
      test P = 0.001). All the three income groups had firmer belief in internal health
      locus of control (mean score less than one out of a total of 4). Though, the mean
      score was highest for the high income group and lowest for the middle income
      group but the difference were not statistically significant. There were no marked
      differences in decision making power of the three groups. CONCLUSION: The results
      of this study document socioeconomic difference in nutrition care potential.
      Though nutrition care potential of housewives was not found to be commendable at
      any income level, the fact that it is low at lower income levels indicates that
      poor nutritional status at lower income level is not because of income only.

PMID- 15449924
TI  - Importance of health education in injury prevention among children.

PMID- 15449925
TI  - Solid cystic papillary epithelial neoplasm of pancreas: a series of three cases
      with review of literature.

PMID- 15449926
TI  - First trimester diagnosis of Meckel Gruber syndrome in pregnancy.

PMID- 15449927
TI  - Negative pressure pulmonary edema: case report.

PMID- 15449928
TI  - Awareness of the process of informed consent among family practice patients in
      Karachi.
AB  - OBJECTIVE: To study the awareness of 'Informed Consent', among patients
      presenting to Family Physicians. METHOD: A cross-sectional study was carried out
      at the Community Health Centre, Aga Khan University Hospital, Karachi in July
      2002. Written Consent was taken and confidentially was assured RESULTS: Out of
      the 100 patients interviewed, 80 agreed to participate in the study, forty-four
      men and thirty-six women. Approximately half the participants (45%) were
      graduates and 40% had less than five years of school education. The awareness of
      the process of 'informed consent' was observed in only 20% of the respondents,
      all in the educational category of graduates. CONCLUSION: A lack of awareness of
      informed consent was observed in patients attending the Community Health Centre,
      Aga Khan University, despite stringent institutional policies, which are
      adequately followed. To improve awareness, 'Health Education Programs' for the
      population are required with media support. Readability of written consent forms
      should be of class V level or less to give advantage to the less educated classes
      in the society. Local languages should be utilized for written and verbal
      consent. Public health programs should also be aimed at educating physicians,
      nurses and paramedics. Provisions should be made to legalise the process of
      taking consent.

PMID- 15449929
TI  - Negatively charged residues and hydrogen bonds tune the ligand histidine pKa
      values of Rieske iron-sulfur proteins.
AB  - Rieske proteins carry a redox-active iron-sulfur cluster, which is bound by two
      histidine and two cysteine side chains. The reduction potential of Rieske
      proteins depends on pH. This pH dependence can be described by two pK(a) values,
      which have been assigned to the two iron-coordinating histidines. Rieske proteins
      are commonly grouped into two major classes: Rieske proteins from quinol
      oxidizing cytochrome bc complexes, in which the ligand histidines titrate in the
      physiological pH range, and bacterial ferredoxin Rieske proteins, in which the
      ligand histidines are protonated at physiological pH. In the study presented
      here, we have calculated pK(a) values of the cluster ligand histidines using a
      combined density functional theory/continuum electrostatics approach.
      Experimental pK(a) values for a bc-type and a ferredoxin Rieske protein could be
      reproduced. We could identify functionally important differences between the two
      proteins: hydrogen bonds toward the cluster, which are present in bc-type Rieske
      proteins, and negatively charged residues, which are present in ferredoxin Rieske
      proteins. We removed these differences by mutating the proteins in our
      calculations. The Rieske centers in the mutated proteins have very similar pK(a)
      values. We thus conclude that the studied structural differences are the main
      reason for the different pH-titration behavior of the proteins. Interestingly,
      the shift caused by neutralizing the negative charges in ferredoxin Rieske
      proteins is larger than the shift caused by removing the hydrogen bonds toward
      the cluster in bc-type Rieske proteins.

PMID- 15449930
TI  - Expression and characterization of the two flavodoxin proteins of Bacillus
      subtilis, YkuN and YkuP: biophysical properties and interactions with cytochrome
      P450 BioI.
AB  - The two flavodoxins (YkuN and YkuP) from Bacillus subtilis have been cloned,
      overexpressed in Escherichia coli and purified. DNA sequencing, mass
      spectrometry, and flavin-binding properties showed that both YkuN and YkuP were
      typical short-chain flavodoxins (158 and 151 amino acids, respectively) and that
      an error in the published B. subtilis genome sequence had resulted in an altered
      reading frame and misassignment of YkuP as a long-chain flavodoxin. YkuN and YkuP
      were expressed in their blue (neutral semiquinone) forms and reoxidized to the
      quinone form during purification. Potentiometry confirmed the strong
      stabilization of the semiquinone form by both YkuN and YkuP (midpoint reduction
      potential for oxidized/semiquinone couple = -105 mV/-105 mV) with respect to the
      hydroquinone (midpoint reduction potential for semiquinone/hydroquinone couple = 
      382 mV/-377 mV). Apoflavodoxin forms were generated by trichloroacetic acid
      treatment. Circular dichroism studies indicated that flavin mononucleotide (FMN)
      binding led to considerable structural rearrangement for YkuP but not for YkuN.
      Both apoflavodoxins bound FMN but not riboflavin avidly, as expected for short
      chain flavodoxins. Structural stability studies with the chaotrope guanidinium
      chloride revealed that there is moderate destabilization of secondary and
      tertiary structure on FMN removal from YkuN, but that YkuP apoflavodoxin has
      similar (or slightly higher) stability compared to the holoprotein. Differential
      scanning calorimetry reveals further differences in structural stability. YkuP
      has a lower melting temperature than YkuN, and its endotherm is composed of a
      single transition, while that for YkuN is biphasic. Optical and fluorimetric
      titrations with oxidized flavodoxins revealed strong affinity (K(d) values
      consistently <5 microM) for their potential redox partner P450 BioI, YkuN showing
      tighter binding. Stopped-flow reduction studies indicated that the maximal
      electron-transfer rate (k(red)) to fatty acid-bound P450 BioI occurs from YkuN
      and YkuP at approximately 2.5 s(-1), considerably faster than from E. coli
      flavodoxin. Steady-state turnover with YkuN or YkuP, fatty acid-bound P450 BioI,
      and E. coli NADPH-flavodoxin reductase indicated that both flavodoxins supported
      lipid hydroxylation by P450 BioI with turnover rates of up to approximately 100
      min(-1) with lauric acid as substrate. Interprotein electron transfer is a likely
      rate-limiting step. YkuN and YkuP supported monohydroxylation of lauric acid and
      myristic acid, but secondary oxygenation of the primary product was observed with
      both palmitic acid and palmitoleic acid as substrates.

PMID- 15449931
TI  - Thermodynamic and biophysical characterization of cytochrome P450 BioI from
      Bacillus subtilis.
AB  - Cytochrome P450 BioI (CYP107H1) from Bacillus subtilis is involved in the early
      stages of biotin synthesis. Previous studies have indicated that BioI can
      hydroxylate fatty acids and may also perform an acyl bond cleavage reaction
      [Green, A. J., Rivers, S. L., Cheesman, M., Reid, G. A., Quaroni, L. G.,
      Macdonald, I. D. G., Chapman, S. K., and Munro, A. W. (2001) J. Biol. Inorg.
      Chem. 6, 523-533. Stok, J. E., and De Voss, J. J. (2000) Arch. Biochem. Biophys.
      384, 351-360]. Here we show novel binding features of P450 BioI--specifically
      that it binds steroids (including testosterone and progesterone) and polycyclic
      azole drugs with similar affinity to that for fatty acids (K(d) values in the
      range 0.1-160 microM). Sigmoidal binding curves for titration of BioI with azole
      drugs suggests a cooperative process in this case. BioI as isolated from
      Escherichia coli is in a mixed heme iron spin state. Alteration of the pH of the
      buffer system affects the heme iron spin-state equilibrium (higher pH increasing
      the low-spin content). Steroids containing a carbonyl group at the C(3) position
      induce a shift in heme iron spin-state equilibrium toward the low-spin form,
      whereas fatty acids produce a shift toward the high-spin form. Electron
      paramagnetic resonance (EPR) studies confirm the heme iron spin-state
      perturbation inferred from optical titrations with steroids and fatty acids.
      Potentiometric studies demonstrate that the heme iron reduction potential becomes
      progressively more positive as the proportion of high-spin heme iron increases
      (potential for low-spin BioI = -330 +/- 1 mV; for BioI as purified from E. coli
      (mixed-spin) = 228 +/- 2 mV; for palmitoleic acid-bound BioI = -199 +/- 2 mV).
      Extraction of bound substrate-like molecule from purified BioI indicates palmitic
      acid to be bound. Differential scanning calorimetry studies indicate that the
      BioI protein structure is stabilized by binding of steroids and bulky azole
      drugs, a result confirmed by resonance Raman studies and by analysis of
      disruption of BioI secondary and tertiary structure by the chaotrope guanidinium
      chloride. Molecular modeling of the BioI structure indicates that a disulfide
      bond is present between Cys250 and Cys275. Calorimetry shows that structural
      stability of the protein was altered by addition of the reductant dithiothreitol,
      suggesting that the disulfide is important to integrity of BioI structure.

PMID- 15449932
TI  - Structure and function of the phenazine biosynthesis protein PhzF from
      Pseudomonas fluorescens 2-79.
AB  - Phenazines, including pyocyanin and iodonin, are biologically active compounds
      that are believed to confer producing organisms with a competitive growth
      advantage, and also are thought to be virulence factors in certain diseases
      including cystic fibrosis. The basic, tricyclic phenazine ring system is
      synthesized in a series of poorly characterized steps by enzymes encoded in a
      seven-gene cistron in Pseudomonas and other organisms. Despite the biological
      importance of these compounds, and our understanding of their mode of action, the
      biochemistry and mechanisms of phenazine biosynthesis are not well resolved. Here
      we report the 1.8 A crystal structure of PhzF, a key enzyme in phenazine
      biosynthesis, solved by molecular replacement. PhzF is structurally similar to
      the lysine biosynthetic enzyme diaminopimelate epimerase, sharing an unusual fold
      consisting of two nearly identical domains with the active site located in an
      occluded cleft between the domains. Unlike diaminopimelate epimerase, PhzF is a
      dimer in solution. The two apparently independent active sites open toward
      opposite sides of the dimer and are occupied by sulfate ions in the structure. In
      vitro experiments using a mixture of purified PhzF, -A, -B, and -G confirm that
      phenazine-1-carboxylic acid (PCA) is readily produced from trans-2,3-dihydro-3
      hydroxyanthranilic acid (DHHA) without aid of other cellular factors. PhzA, -B,
      and -G have no activity toward DHHA. However, in the presence of PhzF,
      individually or in combinations, they accelerate the formation of PCA from DHHA
      and therefore appear to function after the action of PhzF. Surprisingly, PhzF is
      itself capable of producing PCA, albeit slowly, from DHHA. These observations
      suggest that PhzF catalyzes the initial step in the conversion of DHHA to PCA,
      probably via a rearrangement reaction yielding the more reactive 3-oxo analogue
      of DHHA, and that subsequent steps can occur spontaneously. A hypothetical model
      for how DHHA binds to the PhzF active site suggests that Glu45 and Asp208 could
      act as general acid-base catalysts in a rearrangement reaction. Given that four
      reactions lie between DHHA and PCA, ketone formation, ring formation,
      decarboxylation, and oxidation, we hypothesize that the similar PhzA and -B
      proteins catalyze ring formation and thus may be more than noncatalytic accessory
      proteins. PhzG is almost certainly an oxidase and is predicted to catalyze the
      final oxidation/aromatization reaction.

PMID- 15449933
TI  - Inverse electrostatic effect: electrostatic repulsion in the unfolded state
      stabilizes a leucine zipper.
AB  - The pH-dependent stability of a protein is strongly affected by electrostatic
      interactions between ionizable residues in the folded as well as unfolded state.
      Here we characterize the individual contributions of charged Glu and His residues
      to stability and determine the NMR structure of the designed, heterodimeric
      leucine zipper AB consisting of an acidic A chain and a basic B chain.
      Thermodynamic parameters are compared with those of the homologous leucine zipper
      AB(SS) in which the A and B chains are disulfide-linked. NMR structures of AB
      based on (1)H NMR data collected at 600 MHz converge, and formation of the same
      six interchain salt bridges found previously in disulfide-linked AB(SS) [Marti,
      D. N., and Bosshard, H. R. (2003) J. Mol. Biol. 330, 621-637] is indicated. While
      the structures of AB and AB(SS) are very similar, their pH-dependent relative
      stabilities are strikingly different. The stability of AB peaks at pH
      approximately 4.5 and is higher at pH 8 than at pH 2. In contrast, AB(SS) is most
      stable at acidic pH where no interhelical salt bridges are formed. The different
      energetic contributions of charged Glu and His residues to stability of the two
      coiled coil structures were evaluated from pK(a) shifts induced by folding. The
      six charged Glu residues involved in salt bridges stabilize leucine zipper AB by
      4.5 kJ/mol yet destabilize disulfide-linked AB(SS) by -1.1 kJ/mol. Two non-ion
      paired Glu charges destabilize AB by only -1.8 kJ/mol but AB(SS) by -5.6 kJ/mol.
      The higher relative stability of AB at neutral pH is not caused by more favorable
      electrostatic interactions in the folded leucine zipper. It is due mainly to
      unfavorable electrostatic interactions in the unfolded A and B chains and may
      therefore be called an inverse electrostatic effect. This study illustrates the
      importance of residual interactions in the unfolded state and how the energetics
      of the unfolded state affect the stability of the folded protein.

PMID- 15449934
TI  - Long-range dynamic effects of point mutations propagate through side chains in
      the serine protease inhibitor eglin c.
AB  - Long-range interactions are fundamental to protein behaviors such as
      cooperativity and allostery. In an attempt to understand the role protein
      flexibility plays in such interactions, the distribution of local fluctuations in
      a globular protein was monitored in response to localized, nonelectrostatic
      perturbations. Two valine-to-alanine mutations were introduced into the small
      serine protease inhibitor eglin c, and the (15)N and (2)H NMR spin relaxation
      properties of these variants were analyzed in terms of the Lipari-Szabo dynamics
      formalism and compared to those of the wild type. Significant changes in
      picosecond to nanosecond dynamics were observed in side chains located as much as
      13 A from the point of mutation. Additionally, those residues experiencing
      altered dynamics appear to form contiguous surfaces within the protein. In the
      case of V54A, the large-to-small mutation results in a rigidification of
      connected residues, even though this mutation decreases the global stability.
      These findings suggest that dynamic perturbations arising from single mutations
      may propagate away from the perturbed site through networks of interacting side
      chains. That this is observed in eglin c, a classically nonallosteric protein,
      suggests that such behavior will be observed in many, if not all, globular
      proteins. Differences in behavior between the two mutants suggest that dynamic
      responses will be context-dependent.

PMID- 15449935
TI  - Structural investigations of a human calcitonin-derived carrier peptide in a
      membrane environment by solid-state NMR.
AB  - Previous studies have shown that human calcitonin (hCT) and its C-terminal
      fragment hCT(9-32) translocate in nasal epithelium. Moreover, hCT(9-32) was used
      as a carrier to internalize efficiently the green fluorescent protein, drugs, and
      plasmid DNA. To understand the mechanism of the membrane crossing process, we
      determined structural parameters of the carrier peptide hCT(9-32) in a membrane
      environment using solid-state NMR. For that purpose, we synthesized a multiply
      labeled hCT(9-32) peptide comprising four positions with fully (15)N- and (13)C
      labeled amino acids. Multilamellar vesicle samples containing varying mixing
      ratios of hCT(9-32) and phospholipids found in the plasma membrane of nasal
      epithelium were prepared. The typical axially symmetric powder patterns of (31)P
      NMR spectra confirmed the presence of lamellar bilayers in our samples. The
      chemical shift anisotropy of the (31)P NMR spectra of the samples in the presence
      of hCT(9-32) is slightly reduced, revealing weak interaction of the peptide with
      the lipid headgroups. The peptide does not penetrate the lipid membrane as
      indicated by very similar (2)H NMR order parameters of the phospholipid fatty
      acid chains in the absence and presence of the carrier peptide. This membrane
      topology was confirmed by measurements of paramagnetic enhancement of relaxation
      rates. The conformation of hCT(9-32) was investigated by cross polarization magic
      angle spinning NMR methods. All peptide signals were resolved and fully assigned
      in two-dimensional proton-driven (13)C spin diffusion experiments. The isotropic
      chemical shifts of (13)CO, (13)Calpha, and (13)Cbeta provide information about
      the secondary structure of the carrier peptide. The conformation of hCT(9-32) was
      further corroborated by quantitative phi torsion angle measurements. Two
      monomeric structural models are consistent with the data: (i) a linear backbone
      conformation of hCT(9-32) and (ii) an antiparallel beta-sheet structure. These
      structures are maintained over a wide range of peptide:lipid mixing ratios. No
      direct indications for fibril formation of hCT(9-32) were found. Dipolar coupling
      measurements indicate rather high amplitudes of motion of the peptide.

PMID- 15449936
TI  - Solution structure of BmKK4, the first member of subfamily alpha-KTx 17 of
      scorpion toxins.
AB  - BmKK4 is a 30 amino acid peptide purified from the venom of the Chinese scorpion
      Buthus martensi Karsch. It has been classified as the first member of scorpion
      toxin subfamily alpha-KTx 17. The 3D structure of BmKK4 in solution has been
      determined by 2D NMR spectroscopy. This toxin adopts a common alpha/beta-motif,
      but shows a distinctive local conformation. The most novel feature is that the
      regular arrangements of the side chains of the residues involved in the beta
      sheet of BmKK4 are distorted by a classic beta-bulge structure, which involves
      two residues (Asp18 and Arg19) in the first strand opposite a single residue
      (Tyr26) in the second strand. The bulge produces two main changes in the
      structure of the antiparallel beta-sheet: (1) It disrupts the normal alteration
      of the side chain direction; the side chain of Asp18 turns over to form a salt
      bridge with that of Arg19. (2) It accentuates the twist of the sheet, and alters
      the direction of the antiparallel beta-sheet. The unusual structural feature of
      the toxin is attributed to the shorter peptide segment (Leu15-Arg19) between the
      third and fourth Cys residues and two unique residues (Asp18 and Arg19) at the
      position preceding the fourth Cys. In addition, the lower affinity of the peptide
      for the Kv channel is correlated to the structural features: residue Arg19
      instead of a Lys residue at the critical position for binding and the salt bridge
      formed between residues Arg19 and Asp18.

PMID- 15449937
TI  - Crystal structures of HbA2 and HbE and modeling of hemoglobin delta 4:
      interpretation of the thermal stability and the antisickling effect of HbA2 and
      identification of the ferrocyanide binding site in Hb.
AB  - Hemoglobin A(2) (alpha(2)delta(2)) is an important hemoglobin variant which is a
      minor component (2-3%) in the circulating red blood cells, and its elevated
      concentration in beta-thalassemia is a useful clinical diagnostic. In beta
      thalassemia major, where there is beta-chain production failure, HbA(2) acts as
      the predominant oxygen deliverer. HbA(2) has two more important features. (1) It
      is more resistant to thermal denaturation than HbA, and (2) it inhibits the
      polymerization of deoxy sickle hemoglobin (HbS). Hemoglobin E (E26K(beta)),
      formed as a result of the splice site mutation on exon 1 of the beta-globin gene,
      is another important hemoglobin variant which is known to be unstable at high
      temperatures. Both heterozygous HbE (HbAE) and homozygous HbE (HbEE) are benign
      disorders, but when HbE combines with beta-thalassemia, it causes E/beta
      thalassemia which has severe clinical consequences. In this paper, we present the
      crystal structures of HbA(2) and HbE at 2.20 and 1.74 A resolution, respectively,
      in their R2 states, which have been used here to provide the probable
      explanations of the thermal stability and instability of HbA(2) and HbE. Using
      the coordinates of R2 state HbA(2), we modeled the structure of T state HbA(2)
      which allowed us to address the structural basis of the antisickling property of
      HbA(2). Using the coordinates of the delta-chain of HbA(2) (R2 state), we also
      modeled the structure of hemoglobin homotetramer delta(4) that occurs in the case
      of rare HbH disease. From the differences in intersubunit contacts among beta(4),
      gamma(4), and delta(4), we formed a hypothesis regarding the possible
      tetramerization pathway of delta(4). The crystal structure of a ferrocyanide
      bound HbA(2) at 1.88 A resolution is also presented here, which throws light on
      the location and the mode of binding of ferrocyanide anion with hemoglobin,
      predominantly using the residues involved in DPG binding. The pH dependence of
      ferrocyanide binding with hemoglobin has also been investigated.

PMID- 15449938
TI  - Mutation of a lysine residue in a homeodomain generates dominant negative thyroid
      transcription factor 1.
AB  - Thyroid transcription factor 1 (TTF-1) is a 42 kDa homeodomain (HD) containing
      the tissue-specific transcription factor of Nkx2 family members (also termed TEBP
      and Nkx2.1). TTF-1 is an essential transcription factor required for lung
      development and lung-specific gene expression. Transgenic mice carrying TTF-1 DNA
      binding site mutations completely abolish expression of the human surfactant
      protein B (hSP-B) 1.5 kb lacZ reporter gene in the lung in vivo. Acetylation of
      transcription factors by nuclear receptor coactivators is an important mechanism
      for gene regulation. TTF-1 is acetylated by nuclear receptor coactivators
      including the activator of the thyroid and retinoic acid receptor, CREB-binding
      protein, and steroid receptor coactivator 1 (SRC-1) in cell transfection and
      immunoprecipitation studies. A glutathionine transferase pull-down assay shows
      TTF-1 direct interaction with the SRC-1 histone acetyltransferase domain. Site
      specific mutagenesis identifies that the lysine residue at position 182 in the
      TTF-1 HD is acetylated in respiratory epithelial cells. Mutation at this
      acetylation site shows a dominant negative effect on SP-B gene transcription. The
      study supports a concept that acetylation is an important mechanism for TTF-1
      activity.

PMID- 15449939
TI  - Identification of residues of the IFNAR1 chain of the type I human interferon
      receptor critical for ligand binding and biological activity.
AB  - The antiviral and antiproliferative activities of human type I interferons (IFNs)
      are mediated by two transmembrane receptor subunits, IFNAR1 and IFNAR2. To
      elucidate the role of IFNAR1 in IFN binding and the establishment of biological
      activity, specific residues of IFNAR1 were mutated. Residues (62)FSSLKLNVY(70) of
      the S5-S6 loop of the N-terminal subdomain of IFNAR1 and tryptophan-129 of the
      second subdomain of IFNAR1 were shown to be crucial for IFN-alpha binding and
      signaling and establishment of biological activity. Mutagenesis of peptide
      (278)LRV in the third subdomain shows that these residues are critical for IFN
      alpha-induced biological activity but not for ligand binding. These data,
      together with the sequence homology of IFNAR1 with cytokine receptors of known
      structure and the recently resolved NMR structure of IFNAR2, led to the
      establishment of a three-dimensional model of the human IFN-alpha/IFNAR1/IFNAR2
      complex. This model predicts that following binding of IFN to IFNAR1 and IFNAR2
      the receptor complex assumes a "closed form", in which the N-terminal domain of
      IFNAR1 acts as a lid, resulting in the activation of intracellular kinases.
      Differences in the primary sequence of individual IFN-alpha subtypes and
      resulting differences in binding affinity, duration of ligand/receptor
      association, or both would explain differences in intracellular signal
      intensities and biological activity observed for individual IFN-alpha subtypes.

PMID- 15449940
TI  - Effect of the Met344His mutation on the conformational dynamics of bovine beta
      1,4-galactosyltransferase: crystal structure of the Met344His mutant in complex
      with chitobiose.
AB  - Beta-1,4-galactosyltransferase (beta4Gal-T1) in the presence of manganese ion
      transfers galactose from UDP-galactose (UDP-Gal) to N-acetylglucosamine (GlcNAc)
      that is either free or linked to an oligosaccharide. Crystallographic studies on
      bovine beta4Gal-T1 have shown that the primary metal binding site is located in
      the hinge region of a long flexible loop, which upon Mn(2+) and UDP-Gal binding
      changes from an open to a closed conformation. This conformational change creates
      an oligosaccharide binding site in the enzyme. Neither UDP nor UDP analogues
      efficiently induce these conformational changes in the wild-type enzyme, thereby
      restricting the structural analysis of the acceptor binding site. The binding of
      Mn(2+) involves an uncommon coordination to the Sdelta atom of Met344; when it is
      mutated to His, the mutant M344H, in the presence of Mn(2+) and UDP-hexanolamine,
      readily changes to a closed conformation, facilitating the structural analysis of
      the enzyme bound with an oligosaccharide acceptor. Although the mutant M344H
      loses 98% of its Mn(2+)-dependent activity, it exhibits 25% of its activity in
      the presence of Mg(2+). The crystal structures of M344H-Gal-T1 in complex with
      either UDP-Gal.Mn(2+) or UDP-Gal.Mg(2+), determined at 2.3 A resolution, show
      that the mutant enzyme in these complexes is in a closed conformation, and the
      coordination stereochemistry of Mg(2+) is quite similar to that of Mn(2+).
      Although either Mn(2+) or Mg(2+), together with UDP-Gal, binds and changes the
      conformation of the M344H mutant to the closed one, it is the Mg(2+) complex that
      engages efficiently in catalyses. Thus, this property enabled us to crystallize
      the M344H mutant for the first time with the acceptor substrate chitobiose in the
      presence of UDP-hexanolamine and Mn(2+). The crystal structure determined at 2.3
      A resolution reveals that the GlcNAc residue at the nonreducing end of chitobiose
      makes extensive hydrophobic interactions with the highly conserved Tyr286
      residue.

PMID- 15449941
TI  - Engineering of the pH optimum of Bacillus cereus beta-amylase: conversion of the
      pH optimum from a bacterial type to a higher-plant type.
AB  - The optimum pH of Bacillus cereus beta-amylase (BCB, pH 6.7) differs from that of
      soybean beta-amylase (SBA, pH 5.4) due to the substitution of a few amino acid
      residues near the catalytic base residue (Glu 380 in SBA and Glu 367 in BCB). To
      explore the mechanism for controlling the optimum pH of beta-amylase, five
      mutants of BCB (Y164E, Y164F, Y164H, Y164Q, and Y164Q/T47M/Y164E/T328N) were
      constructed and characterized with respect to enzymatic properties and X-ray
      structural crystal analysis. The optimum pH of the four single mutants shifted to
      4.2-4.8, approximately 2 pH units and approximately 1 pH unit lower than those of
      BCB and SBA, respectively, and their k(cat) values decreased to 41-3% of that of
      the wild-type enzyme. The X-ray crystal analysis of the enzyme-maltose complexes
      showed that Glu 367 of the wild type is surrounded by two water molecules (W1 and
      W2) that are not found in SBA. W1 is hydrogen-bonded to both side chains of Glu
      367 and Tyr 164. The mutation of Tyr 164 to Glu and Phe resulted in the
      disruption of the hydrogen bond between Tyr 164 Oeta and W1 and the introduction
      of two additional water molecules near position 164. In contrast, the triple
      mutant of BCB with a slightly decreased pH optimum at pH 6.0 has no water
      molecules (W1 and W2) around Glu 367. These results suggested that a water
      mediated hydrogen bond network (Glu 367...W1...Tyr 164...Thr 328) is the primary
      requisite for the increased pH optimum of wild-type BCB. This strategy is
      completely different from that of SBA, in which a hydrogen bond network (Glu
      380...Thr 340...Glu 178) reduces the optimum pH in a hydrophobic environment.

PMID- 15449942
TI  - Internal friction controls the speed of protein folding from a compact
      configuration.
AB  - Several studies have found millisecond protein folding reactions to be controlled
      by the viscosity of the solvent: Reducing the viscosity allows folding to
      accelerate. In the limit of very low solvent viscosity, however, one expects a
      different behavior. Internal interactions, occurring within the solvent-excluded
      interior of a compact molecule, should impose a solvent-independent upper limit
      to folding speed once the bulk diffusional motions become sufficiently rapid. Why
      has this not been observed? We have studied the effect of solvent viscosity on
      the folding of cytochrome c from a highly compact, late-stage intermediate
      configuration. Although the folding rate accelerates as the viscosity declines,
      it tends toward a finite limiting value approximately 10(5) s(-1) as the
      viscosity tends toward zero. This limiting rate is independent of the cosolutes
      used to adjust solvent friction. Therefore, interactions within the interior of a
      compact denatured polypeptide can limit the folding rate, but the limiting time
      scale is very fast. It is only observable when the solvent-controlled stages of
      folding are exceedingly rapid or else absent. Interestingly, we find a very
      strong temperature dependence in these "internal friction"-controlled dynamics,
      indicating a large energy scale for the interactions that govern reconfiguration
      within compact, near-native states of a protein.

PMID- 15449943
TI  - Structures of the Escherichia coli PutA proline dehydrogenase domain in complex
      with competitive inhibitors.
AB  - Proline dehydrogenase (PRODH) catalyzes the first step of proline catabolism, the
      flavin-dependent oxidation of proline to Delta(1)-pyrroline-5-carboxylate. Here
      we present a structure-based study of the PRODH active site of the
      multifunctional Escherichia coli proline utilization A (PutA) protein using X-ray
      crystallography, enzyme kinetic measurements, and site-directed mutagenesis.
      Structures of the PutA PRODH domain complexed with competitive inhibitors acetate
      (K(i) = 30 mM), L-lactate (K(i) = 1 mM), and L-tetrahydro-2-furoic acid (L-THFA,
      K(i) = 0.2 mM) have been determined to high-resolution limits of 2.1-2.0 A. The
      discovery of acetate as a competitive inhibitor suggests that the carboxyl is the
      minimum functional group recognized by the active site, and the structures show
      how the enzyme exploits hydrogen-bonding and nonpolar interactions to optimize
      affinity for the substrate. The PRODH/L-THFA complex is the first structure of
      PRODH with a five-membered ring proline analogue bound in the active site and
      thus provides new insights into substrate recognition and the catalytic
      mechanism. The ring of L-THFA is nearly parallel to the middle ring of the FAD
      isoalloxazine, with the inhibitor C5 atom 3.3 A from the FAD N5. This geometry
      suggests direct hydride transfer as a plausible mechanism. Mutation of conserved
      active site residue Leu432 to Pro caused a 5-fold decrease in k(cat) and a severe
      loss in thermostability. These changes are consistent with the location of Leu432
      in the hydrophobic core near residues that directly contact FAD. Our results
      suggest that the molecular basis for increased plasma proline levels in
      schizophrenic subjects carrying the missense mutation L441P is due to decreased
      stability of human PRODH2.

PMID- 15449944
TI  - Accommodation of mispair aligned N3T-ethyl-N3T DNA interstrand cross link.
AB  - The solution structure of the undecamer d(CGAAATTTTCG)(2), where T represents a
      N(3)T-ethyl-N(3)T interstrand cross link, was elucidated using molecular dynamics
      calculations restrained by NOE and dihedral data obtained from NMR spectroscopy.
      The ethyl moiety is particularly well-accommodated between the minor and major
      grooves. This is an exceptional example of the plasticity along the axis defined
      by the stem and a unique finding of an interstrand cross link occupying the area
      associating minor and major grooves. The mismatch-aligned tethered bases preserve
      good intrastrand stacking with flanking bases. Base-pair steps adjacent to the
      lesion site are overwound. Accommodation of the lesion also results in an
      increase in mispair staggering alignment modulated by flexibility because of the
      tetrahedral geometry of the exocyclic ethyl carbon atoms. This is mechanically
      coupled with a small measure of concomitant propeller twisting without an
      increase in intrastrand base-step distance. Both x displacement and sugar
      puckering are indicative of canonical B DNA throughout the stem. We have thus
      established that the lesion defined by mismatch-aligned minor groove N(3)T-ethyl
      N(3)T cross-linked thymine bases produces very localized distortions in a DNA
      stem that may be difficult to recognize by repair mechanisms that are not
      transcription- or replication-coupled. Thus, this synthetic DNA is a valuable
      structural probe to study mechanisms of repair.

PMID- 15449945
TI  - Structure of three class I human alcohol dehydrogenases complexed with isoenzyme
      specific formamide inhibitors.
AB  - Formamides are aldehyde analogues that have demonstrated potent and selective
      inhibition of human alcohol dehydrogenase isoenzymes. The alphaalpha,
      beta(1)beta(1), gamma(2)gamma(2), and sigmasigma isoforms have all been found to
      be strongly inhibited by substituted formamides. In this paper, the structure of
      the alphaalpha isoform of human alcohol dehydrogenase complexed with N
      cyclopentyl-N-cyclobutylformamide was determined by X-ray crystallography to 2.5
      A resolution, the beta(1)beta(1) isoform of human alcohol dehydrogenase complexed
      with N-benzylformamide and with N-heptylformamide was determined to 1.6 and 1.65
      A resolution, respectively, and the structure of the gamma(2)gamma(2) isoform
      complexed with N-1-methylheptylformamide was determined to 1.45 A resolution.
      These structures provide the first substrate-level view of the local structural
      differences that give rise to the individual substrate preferences shown by these
      highly related isoenzymes. Consistent with previous work, the carbonyl oxygen of
      the inhibitors interacts directly with the catalytic zinc and the hydroxyl group
      of Thr48 (Ser48 for gamma(2)gamma(2)) of the enzyme. The benzene ring of N
      benzylformamide and the carbon chains of N-heptylformamide and N-1
      methylheptylformamide interact with the sides of the hydrophobic substrate pocket
      whose size and shape is dictated by residue exchanges between the beta(1)beta(1)
      and gamma(2)gamma(2) isoenzymes. In particular, the exchange of Ser for Thr at
      position 48 and the exchange of Val for Leu at position 141 in the
      gamma(2)gamma(2) isoenzyme create an environment with stereoselectivity for the R
      enantiomer of the branched N-1-methylheptylformamide inhibitor in this isoenzyme.
      The primary feature of the alphaalpha isoform is the Ala for Phe93 exchange that
      enlarges the active site near the catalytic zinc and creates the specificity for
      the branched N-cyclopentyl-N-cyclobutylformamide inhibitor, which shows the
      greatest selectivity for this unique isoenzyme of any of the formamide
      inhibitors.

PMID- 15449946
TI  - Effects of a novel disulfide bond and engineered electrostatic interactions on
      the thermostability of azurin.
AB  - Identification and evaluation of factors important for thermostability in
      proteins is a growing research field with many industrial applications. This
      study investigates the effects of introducing a novel disulfide bond and
      engineered electrostatic interactions with respect to the thermostability of holo
      azurin from Pseudomonas aeruginosa. Four mutants were selected on the basis of
      rational design and novel temperature-dependent atomic displacement factors from
      crystal data collected at elevated temperatures. The atomic displacement
      parameters describe the molecular movement at higher temperatures. The
      thermostability was evaluated by optical spectroscopy as well as by differential
      scanning calorimetry. Although azurin has a high inherent stability, the
      introduction of a novel disulfide bond connecting a flexible loop with small
      alpha-helix (D62C/K74C copper-containing mutant), increased the T(m) by 3.7
      degrees C compared with the holo protein. Furthermore, three mutants were
      designed to introduce electrostatic interactions, K24R, D23E/K128R, and
      D23E/K128R/K24R. Mutant K24R stabilizes loops between two separate beta-strands
      and D23E/K128R was selected to stabilize the C-terminus of azurin. Furthermore,
      D23E/K128R/K24R was selected to reflect the combination of the electrostatic
      interactions in D23E/K128R and K24R. The mutants involving electrostatic
      interactions had a minor effect on the thermostability. The crystal structures of
      the copper-containing mutants D62C/K74C and K24R have been determined to 1.5 and
      1.8 A resolution. In addition the crystal structure of the zinc-loaded mutant
      D62C/K74C has also been completed to 1.8 A resolution. These structures support
      the selected design and provide valuable information for evaluating effects of
      the modifications on the thermostability of holo azurin.

PMID- 15449947
TI  - Selection of active ScFv to G-protein-coupled receptor CCR5 using surface antigen
      mimicking peptides.
AB  - This study describes the use of cyclic peptides for use in the selection of
      single-chain (ScFv) antibodies specific for the HIV-1 coreceptor CCR5, a
      representative G-protein-coupled receptor (GPCR). A tandem ligation strategy was
      developed for preparing biotinylated cyclic peptides, first through an orthogonal
      end-to-end ligation and then a chemoselective ligation with functionalized
      biotin. Cyclic peptides mimicking the extracellular loops of CCR5 and their
      unconstrained counterparts were then used for solution-phase selection of ScFv
      antibodies from a phage display antibody library. Antibodies reactive with CCR5
      on cells were detected using a homogeneous high throughput assay. Of 19 isolated
      ScFv antibodies that bound to CCR5+ cells, three inhibited CCR5-mediated but not
      CXCR4-mediated HIV infection. Only ScFvs selected by binding to cyclic
      constrained peptides exhibited inhibitory activity. Our results demonstrate that
      surface-antigen mimetics of a GPCR are effective tools for selecting active, site
      specific ScFv antibodies that hold promise as immunological reagents and
      therapeutics.

PMID- 15449948
TI  - Cell-free synthesis of a functional ion channel in the absence of a membrane and
      in the presence of detergent.
AB  - We have investigated the possibility of cell-fee synthesis of membrane proteins
      in the absence of a membrane and in the presence of detergent. We used the
      bacterial mechanosensitive channel MscL, a homopentamer, as a model protein. A
      wide range of nonionic or zwitterionic detergents, Triton X-100, Tween 20, Brij
      58p, n-dodecyl beta-D-maltoside, and CHAPS, were compatible with cell-free
      synthesis, while n-octyl beta-D-glucoside and deoxycholate had an inhibitory
      effect. In vitro synthesis in the presence of Triton X-100 yielded milligram
      amounts of MscL per milliliter of lysate. Cross-linking experiments showed that
      the protein was able to oligomerize in detergents. When the purified protein was
      reconstituted in liposomes and studied by the patch-clamp technique, its activity
      at the single-molecule level was similar to that of the recombinant protein
      produced in Escherichia coli. Cell-free synthesis of membrane proteins should
      prove a valuable tool for the production of membrane proteins whose
      overexpression in heterologous systems is difficult.

PMID- 15449949
TI  - Sterol carrier protein-2-facilitated intermembrane transfer of cholesterol- and
      phospholipid-derived hydroperoxides.
AB  - Sterol carrier protein-2 (SCP-2) facilitates cholesterol (Ch) and phospholipid
      (PL) transfer/exchange between membranes and appears to play a key role in
      intracellular lipid trafficking. Whether SCP-2 can also facilitate lipid
      hydroperoxide (LOOH) transfer between membranes and thereby potentially enhance
      dissemination of peroxidative damage was examined in this study. Transfer
      kinetics of photochemically generated cholesterol hydroperoxide (ChOOH) species
      (5alpha-OOH, 6alpha/6beta-OOH, 7alpha/7beta-OOH) and phospholipid hydroperoxide
      (PLOOH) families (PCOOH, PEOOH, PSOOH) were determined, using HPLC with
      electrochemical detection for peroxide analysis. LOOH donor/acceptor pairs
      employed in transfer experiments included (i) all liposomes (e.g., agglutinable
      SUVs/ nonagglutinable LUVs); (ii) photoperoxidized erythrocyte ghosts/SUVs or
      vice versa; and (iii) SUVs/mitochondria. In a SUV/ghost system at 37 degrees C,
      the rate constant for total ChOOH spontaneous transfer was approximately 8 times
      greater than that for unoxidized Ch. Purified bovine liver and human recombinant
      SCP-2 exhibited an identical ability to stimulate overall ChOOH transfer, 0.5
      unit/mL (based on [(14)C]Ch transfer) increasing the first-order rate constant
      (k) approximately 7-fold. SCP-2-enhanced translocation of individual ChOOHs
      increased with increasing hydrophilicity in the following order: 6beta-OOH <
      6alpha-OOH < 5alpha-OOH < 7alpha/7beta-OOH. Likewise, SCP-2 stimulated PCOOH,
      PEOOH, or PSOOH transfer approximately 6-fold, but the net k was 1/5 that of
      5alpha-OOH and 1/10 that of 7alpha/7beta-OOH. Donor membrane properties favoring
      SCP-2-enhanced LOOH transfer included (i) increasing PL unsaturation and (ii)
      increasing net negative charge imposed by phosphatidylserine. Cytotoxic relevance
      was demonstrated by showing that SCP-2 accelerates 7alpha-OOH transfer from SUVs
      to isolated mitochondria and that this enhances peroxide-induced loss of the
      mitochondrial membrane potential. On the basis of these findings, we postulate
      that SCP-2, by trafficking ChOOHs and PLOOHs in addition to parent lipids, might
      exacerbate cell injury under oxidative stress conditions.

PMID- 15449950
TI  - Sugar binding induced charge translocation in the melibiose permease from
      Escherichia coli.
AB  - Electrogenic events associated with the activity of the melibiose permease
      (MelB), a transporter from Escherichia coli, were investigated. Proteoliposomes
      containing purified MelB were adsorbed to a solid supported lipid membrane,
      activated by a substrate concentration jump, and transient currents were
      measured. When the transporter was preincubated with Na(+) at saturating
      concentrations, a charge translocation in the protein upon melibiose binding
      could still be observed. This result demonstrates that binding of the uncharged
      substrate melibiose triggers a charge displacement in the protein. Further
      analysis showed that the charge displacement is neither related to extra Na(+)
      binding to the transporter, nor to the displacement of already bound Na(+) within
      the transporter. The electrogenic melibiose binding process is explained by a
      conformational change with concomitant displacement of charged amino acid side
      chains and/or a reorientation of helix dipoles. A kinetic model is suggested, in
      which Na(+) and melibiose binding are distinct electrogenic processes associated
      with approximately the same charge displacement. These binding reactions are fast
      in the presence of the respective cosubstrate (k > 50 s(-1)).

PMID- 15449951
TI  - Time-resolved photointermediate changes in rhodopsin glutamic acid 181 mutants.
AB  - The role of glutamic acid 181 in the bovine rhodopsin retinylidene chromophore
      pocket was studied by expressing E181 mutants in COS cells and measuring, as a
      function of time, the absorbance changes produced after excitation of lauryl
      maltoside pigment suspensions with 7 ns laser pulses. All mutants studied except
      E181D showed accelerated decay of bathorhodopsin compared to wild type. Even for
      E181D, an anomalously large blue shift was observed in the absorption spectrum of
      the bathorhodopsin decay product, BSI. These observations support the idea that
      E181 plays a significant role in the earliest stages of receptor activation. E181
      mutations have a pronounced effect on the decay of the lumirhodopsin
      photointermediate, primarily affecting the size of the red shift that occurs in
      the lumirhodopsin I to lumirhodopsin II transition that takes place on the 10
      micros time scale after wild-type photoexcitation. While the spectral change that
      occurs in the lumirhodopsin I to lumirhodopsin II transition in wild-type
      rhodopsin is very small ( approximately 2 nm), making it difficult to detect, it
      is larger in E181D ( approximately 6 nm), making it evident even in the lower
      signal-to-noise ratio measurements possible with rhodopsin mutants. The change
      seen is even larger for the E181F mutant where significant amounts of a
      deprotonated Schiff base intermediate are produced with the 10 micros time
      constant of lumirhodopsin II formation. The E181Q mutant shows lumirhodopsin
      decay more similar to wild-type behavior, and no lumirhodopsin I to lumirhodopsin
      II transition can be resolved. The addition of chloride ion to E181Q increases
      the lumirhodopsin I-lumirhodopsin II spectral shift and slows the deprotonation
      of the Schiff base. The latter result is consistent with the idea that a negative
      charge at position 181 contributes to protonated Schiff base stability in the
      later intermediates.

PMID- 15449952
TI  - Cyanide binding to hexacoordinate cyanobacterial hemoglobins: hydrogen-bonding
      network and heme pocket rearrangement in ferric H117A Synechocystis hemoglobin.
AB  - The truncated hemoglobin (Hb) from the cyanobacterium Synechocystis sp. PCC 6803
      is a bis-histidyl hexacoordinate complex in the absence of exogenous ligands.
      This protein can form a covalent cross-link between His117 in the H-helix and the
      heme 2-vinyl group. Cross-linking, the physiological importance of which has not
      been established, is avoided with the His117Ala substitution. In the present
      work, H117A Hb was used to explore exogenous ligand binding to the heme group.
      NMR and thermal denaturation data showed that the replacement was of little
      consequence to the structural and thermodynamic properties of ferric
      Synechocystis Hb. It did, however, decelerate the association of cyanide ions
      with the heme iron. Full complexation required hours, instead of minutes, of
      incubation at optical and NMR concentrations. At neutral pH and in the presence
      of excess cyanide, binding occurred with a first-order dependence on cyanide
      concentration, eliminating distal histidine decoordination as the rate-limiting
      step. The cyanide complex of the H117A variant was characterized for the
      conformational changes occurring as the histidine on the distal side, His46
      (E10), was displaced. Extensive rearrangement allowed Tyr22 (B10) to insert in
      the heme pocket and Gln43 (E7) and Gln47 (E11) to come in contact with it. H-bond
      formation to the bound cyanide was identified in solution with the use of
      (1)H(2)O/(2)H(2)O mixtures. Cyanide binding also resulted in a change in the
      ratio of heme orientational isomers, in a likely manifestation of heme
      environment reshaping. Similar observations were made with the related
      Synechococcus sp. PCC 7002 H117A Hb, except that cyanide binding was rapid in
      this protein. In both cases, the (15)N chemical shift of bound cyanide was
      reminiscent of that in peroxidases and the orientation of the proximal histidine
      was as in other truncated Hbs. The ensemble of the data provided insight into the
      structural cooperativity of the heme pocket scaffold and pointed to the reactive
      117 site of Synechocystis Hb as a potential determinant of biophysical and,
      perhaps, functional properties.

PMID- 15449953
TI  - Mutation of the putative hydrogen-bond donor to P700 of photosystem I.
AB  - The primary electron donor of photosystem I (PS1), called P(700), is a
      heterodimer of chlorophyll (Chl) a and a'. The crystal structure of photosystem I
      reveals that the chlorophyll a' (P(A)) could be hydrogen-bonded to the protein
      via a threonine residue, while the chlorophyll a (P(B)) does not have such a
      hydrogen bond. To investigate the influence of this hydrogen bond on P(700), PsaA
      Thr739 was converted to alanine to remove the H-bond to the 13(1)-keto group of
      the chlorophyll a' in Chlamydomonas reinhardtii. The PsaA-T739A mutant was
      capable of assembling active PS1. Furthermore the mutant PS1 contained
      approximately one chlorophyll a' molecule per reaction center, indicating that
      P(700) was still a Chl a/a' heterodimer in the mutant. However, the mutation
      induced several band shifts in the visible P(700)(+) - P(700) absorbance
      difference spectrum. Redox titration of P(700) revealed a 60 mV decrease in the
      P(700)/P(700)(+) midpoint potential of the mutant, consistent with loss of a H
      bond. Fourier transform infrared (FTIR) spectroscopy indicates that the ground
      state of P(700) is somewhat modified by mutation of ThrA739 to alanine.
      Comparison of FTIR difference band shifts upon P(700)(+) formation in WT and
      mutant PS1 suggests that the mutation modifies the charge distribution over the
      pigments in the P(700)(+) state, with approximately 14-18% of the positive charge
      on P(B) in WT being relocated onto P(A) in the mutant. (1)H-electron-nuclear
      double resonance (ENDOR) analysis of the P(700)(+) cation radical was also
      consistent with a slight redistribution of spin from the P(B) chlorophyll to
      P(A), as well as some redistribution of spin within the P(B) chlorophyll. High
      field electron paramagnetic resonance (EPR) spectroscopy at 330-GHz was used to
      resolve the g-tensor of P(700)(+), but no significant differences from wild-type
      were observed, except for a slight decrease of anisotropy. The mutation did,
      however, provoke changes in the zero-field splitting parameters of the triplet
      state of P(700) ((3)P(700)), as determined by EPR. Interestingly, the mutation
      induced change in asymmetry of P(700) did not cause an observable change in the
      directionality of electron transfer within PS1.

PMID- 15449954
TI  - Effects of deletion and site-directed mutations on ligation steps of NAD+
      dependent DNA ligase: a biochemical analysis of BRCA1 C-terminal domain.
AB  - DNA strand joining entails three consecutive steps: enzyme adenylation to form
      AMP-ligase, substrate adenylation to form AMP-DNA, and nick closure. In this
      study, we investigate the effects on ligation steps by deletion and site-directed
      mutagenesis of the BRCA1 C-terminal (BRCT) domain using NAD(+)-dependent DNA
      ligase from Thermus species AK16D. Deletion of the BRCT domain resulted in
      substantial loss of ligation activity, but the mutant was still able to form an
      AMP-ligase intermediate, suggesting that the defects caused by deletion of the
      entire BRCT domain occur primarily at steps after enzyme adenylation. The lack of
      AMP-DNA accumulation by the domain deletion mutant as compared to the wild-type
      ligase indicates that the BRCT domain plays a role in the substrate adenylation
      step. Gel mobility shift analysis suggests that the BRCT domain and helix-hairpin
      helix subdomain play a role in DNA binding. Similar to the BRCT domain deletion
      mutant, the G617I mutant showed a low ligation activity and lack of accumulation
      of AMP-DNA intermediate. However, the G617I mutant was only weakly adenylated,
      suggesting that a point mutation in the BRCT domain could also affect the enzyme
      adenylation step. The significant reduction of ligation activity by G634I appears
      to be attributable to a defect at the substrate adenylation step. The greater
      ligation of mismatched substrates by G638I is accountable by accelerated
      conversion of the AMP-DNA intermediate to a ligation product at the final nick
      closure step. The mutational effects of the BRCT domain on ligation steps in
      relation to protein-DNA and potential protein-protein interactions are discussed.

PMID- 15449955
TI  - Nucleotide-dependent isomerization of Escherichia coli RNA polymerase.
AB  - During promoter engagement, RNA polymerase must change conformation or isomerize
      to its active form. These data show that high concentrations of nucleotides
      assist this isomerization. When binding to fork junction DNA probes is monitored,
      isomerization can occur without the need for the DNA that overlaps the
      transcription start site. When the start site is present, nucleoside
      triphosphates cause polymerase to change conformation in a way that drives cross
      linking to the +1 position on the template strand. Preincubation of transcription
      complexes with 2 mM initiating nucleotide can drive formation of heparin
      resistant complexes under conditions in which isomerization is limiting. It is
      proposed that complete polymerase isomerization can require nucleotide binding,
      which can assist formation of the active site that engages the transcription
      start site.

PMID- 15449956
TI  - Oleic acid derived metabolites in mouse neuroblastoma N18TG2 cells.
AB  - Oleamide is an endogenous sleep-inducing lipid that has been isolated from the
      cerebrospinal fluid of sleep-deprived mammals. Oleamide is the best-understood
      member of the primary fatty acid amide family. One key unanswered question
      regarding oleamide and all other primary acid amides is the pathway by which
      these molecules are produced. One proposed pathway involves oleoyl-CoA and N
      oleoylglycine as intermediates: oleic acid --> oleoyl-CoA --> N-oleoylglycine -->
      oleamide. The first and third reactions are known reactions, catalyzed by acyl
      CoA synthetase and peptidylglycine alpha-amidating monooxygenase (PAM). Oleoyl
      CoA formation from oleic acid has been demonstrated in vitro and in vivo while,
      to date, N-oleoylglycine cleavage to oleamide has been established only in vitro.
      PAM catalyzes the final step in alpha-amidated peptide biosynthesis, and its
      proposed role in primary fatty acid amide biosynthesis has been controversial.
      Mouse neuroblastoma N(18)TG(2) cells are an excellent model system for the study
      of oleamide biosynthesis because these cells convert [(14)C]-oleic acid to
      [(14)C]-oleamide and express PAM in a regulated fashion. We report herein that
      growth of the N(18)TG(2) cells in the presence of [(14)C]-oleic acid under
      conditions known to stimulate PAM expression generates an increase in [(14)C]
      oleamide or in the presence of a PAM inhibitor generates [(14)C]-N-oleoylglycine.
      This represents the first identification of N-oleoylglycine from a biological
      source. In addition, N(18)TG(2) cell growth in the presence of N-oleoylglycine
      yields oleamide. These results strongly indicate that N-oleoylglycine is an
      intermediate in oleamide biosynthesis and provide further evidence that PAM does
      have a role in primary fatty acid amide production in vivo.

PMID- 15449957
TI  - Binding of volatile anesthetics to serum albumin: measurements of enthalpy and
      solvent contributions.
AB  - This study directly examines the enthalpic contributions to binding in aqueous
      solution of closely related anesthetic haloethers (desflurane, isoflurane,
      enflurane, and sevoflurane), a haloalkane (halothane), and an intravenous
      anesthetic (propofol) to bovine and human serum albumin (BSA and HSA) using
      isothermal titration calorimetry. Binding to serum albumin is exothermic,
      yielding enthalpies (DeltaH(obs)) of -3 to -6 kcal/mol for BSA with a rank order
      of apparent equilibrium association constants (K(a) values): desflurane >
      isoflurane approximately enflurane > halothane >or= sevoflurane, with the
      differences being largely ascribed to entropic contributions. Competition
      experiments indicate that volatile anesthetics, at low concentrations, share the
      same sites in albumin previously identified in crystallographic and photo-cross
      linking studies. The magnitude of the observed DeltaH increased linearly with
      increased reaction temperature, reflecting negative changes in heat capacities
      (DeltaC(p)). These -DeltaC(p) values significantly exceed those calculated for
      burial of each anesthetic in a hydrophobic pocket. The enhanced stabilities of
      the albumin/anesthetic complexes and -DeltaC(p) are consistent with favorable
      solvent rearrangements that promote binding. This idea is supported by
      substitution of D(2)O for H(2)O that significantly reduces the favorable binding
      enthalpy observed for desflurane and isoflurane, with an opposing increase of
      DeltaS(obs). From these results, we infer that solvent restructuring, resulting
      from release of water weakly bound to anesthetic and anesthetic-binding sites, is
      a dominant and favorable contributor to the enthalpy and entropy of binding to
      proteins.

PMID- 15449958
TI  - Pig muscle carnitine palmitoyltransferase I (CPTI beta), with low Km for
      carnitine and low sensitivity to malonyl-CoA inhibition, has kinetic
      characteristics similar to those of the rat liver (CPTI alpha) enzyme.
AB  - The outer mitochondrial membrane enzyme carnitine palmitoyltransferase I (CPTI)
      catalyzes the initial and regulatory step in the beta-oxidation of long-chain
      fatty acids. There are two well-characterized isotypes of CPTI: CPTIalpha (also
      known as L-CPTI) and CPTIbeta (also known as M-CPTI) that in human and rat encode
      for enzymes with very different kinetic properties and sensitivity to malonyl-CoA
      inhibition. Kinetic hallmarks of the CPTIalpha are high affinity for carnitine
      and low sensitivity to malonyl-CoA inhibition, while the opposite
      characteristics, low affinity for carnitine and high sensitivity to malonyl-CoA,
      are intrinsic to the CPTIbeta isotype. We have isolated the pig CPTIbeta cDNA
      which encodes for a protein of 772 amino acids that shares extensive sequence
      identity with human (88%), rat (85%), and mouse (86%) CPTIbeta, while the degree
      of homology with the CPTIalpha from human (61%), rat (62%), and mouse (60%) is
      much lower. However, when expressed in the yeast Pichia pastoris, pig CPTIbeta
      shows kinetic characteristics similar to those of the CPTIalpha isotype. Thus,
      the pig CPTIbeta, unlike the corresponding human or rat enzyme, has a high
      affinity for carnitine (K(m) = 197 microM) and low sensitive to malonyl-CoA
      inhibition (IC(50) = 906 nM). Therefore, the recombinant pig CPTIbeta has unique
      kinetic characteristics, which makes it a useful model to study the structure
      function relationship of the CPTI enzymes.

PMID- 15449959
TI  - Purification and physical-chemical characterization of the three hydroperoxidases
      from the symbiotic bacterium Sinorhizobium meliloti.
AB  - Three genes encoding heme hydroperoxidases (katA, katB, and katC) have been
      identified in the soil bacterium Sinorhizobium meliloti. The recombinant proteins
      were overexpressed in Escherichia coli and purified in order to achieve a
      spectral and kinetic characterization. The three proteins contain heme b with
      high-spin Fe(III). KatB is an acidic bifunctional homodimeric catalase-peroxidase
      exhibiting both catalase (k(cat) = 2400 s(-1)) and peroxidase activity and having
      a high affinity for hydrogen peroxide (apparent K(M) = 1.6 mM). KatA and KatC are
      acidic monofunctional homotetrameric catalases. Although different in size (KatA
      is a small subunit catalase while KatC is a large subunit catalase) both enzymes
      exhibit the same heme type and a similar affinity for H(2)O(2) (apparent K(M)
      values of 160 and 150 mM). However, the turnover rate of KatA (k(cat) = 279000 s(
      1)) exceeds that of KatC (k(cat) = 3100 s(-1)) significantly. The kinetic
      parameters are in good agreement with the physiological role of these heme
      proteins. KatB is the housekeeping hydroperoxidase exhibiting the highest
      affinity for hydrogen peroxide, while KatA has the lowest H(2)O(2) affinity but
      the highest k(cat)/K(M) value (1.75 x 10(6) M(-1) s(-1)), in agreement with the
      hydrogen peroxide inducibility of the encoding gene. Moreover, the lower
      catalytic efficiency of KatC (2.1 x 10(4) M(-1) s(-1)) appears to be enough for
      growing in the stationary phase and/or under heat or salt stress (conditions that
      are known to favor katC expression).

PMID- 15449960
TI  - Alpha-conotoxin residues that interact at close range with gamma-tyrosine-111 and
      mutant delta-tyrosine-113 on the Torpedo nicotinic acetylcholine receptor.
AB  - The alpha-conotoxins MI and GI display stronger affinities for the alphagamma
      agonist site on the Torpedo californica electrocyte nicotinic acetylcholine
      receptor (ACHR) than for the alphadelta agonist site, while alpha-conotoxin SI
      binds with the same affinity to both sites. Prior studies reported that the
      arginine at position 9 on GI and the tyrosine at position 111 on the receptor
      gamma subunit were responsible for the stronger alphagamma affinities of GI and
      MI, respectively. This study was undertaken to determine if the alpha-conotoxin
      midchain cationic residues interact with Torpedo gammaY111. The findings show
      that lysine 10 on MI is responsible for the alphagamma selectivity of MI and
      confirm the previously reported importance of R9 on GI and on the SI analogue,
      SIP9R. The results also show that gammaY111 contributes substantially to the
      selective alphagamma high affinity of all three peptides. Double-mutant cycle
      analyses reveal that, in the alphagamma site, K10 on MI and R9 on SIP9R interact
      with the aromatic ring of gammaY111 to stabilize the high-affinity complex, while
      in contrast, R9 on GI does not. The substitution of Y for R at position 113 on
      the delta subunit converts the alphadelta site into a high-affinity site for MI,
      GI, and SIP9R through the interacting of deltaY113 with K10 on MI and with R9 on
      both GI and SIP9R. The overall data show that the residues in the two sites with
      which MI interacts, other than at gamma111/delta113, are either the same or
      similar enough to exert equivalent effects on MI, indicating that MI binds in the
      same orientation at the alphagamma and alphadelta sites. Similar findings show
      that SIP9R probably also binds in the same orientation at the wild-type
      alphagamma and alphadelta sites. The finding that R9 on GI interacts closely with
      deltaR113Y but not with gammaY111 means that GI binds in different orientations
      at the alphagamma and alphadelta sites. This report also discusses the molecular
      basis of the difference in the MI high-affinity sites on Torpedo and embryonic
      mouse muscle ACHRs.

PMID- 15449961
TI  - Cost effectiveness of ramipril in patients at high risk for cardiovascular events
      : economic evaluation of the HOPE (Heart Outcomes Prevention Evaluation) study
      for Germany from the Statutory Health Insurance perspective.
AB  - BACKGROUND: In the HOPE (Heart Outcomes Prevention Evaluation) trial, ramipril
      (compared with placebo) significantly reduced cardiovascular death and all-cause
      mortality as well as the incidence of costly cardiovascular events, such as
      myocardial infarction, revascularisation, stroke, cardiac arrest, hospitalisation
      due to heart failure and worsening angina pectoris, new-onset diabetes mellitus
      and microvascular diabetic complications. OBJECTIVE: Data from the HOPE study
      were used in a cost-effectiveness analysis to determine the additional cost per
      life-year gained (LYG) when the ACE inhibitor ramipril was added to the current
      medication of patients at high risk for cardiovascular events. The aim was to
      establish the incremental cost-effectiveness ratio (ICER) of ramipril versus
      placebo from the perspective of the Statutory Health Insurance (SHI) provider in
      Germany, for both the study population as a whole and for the subgroup of
      patients with diabetes. DESIGN: A modelling approach was used, based on secondary
      analysis of published data and retrospective application of costs. In the base
      case analysis, average case-related expenses of the SHI were applied and LYG were
      quantified using the average of the difference between the survival rates in the
      ramipril and placebo groups during the HOPE trial. LYG beyond the trial duration
      were estimated by the method of declining exponential approximation of life
      expectancy. RESULTS: After a treatment period of 4.5 years, the ICER of ramipril
      versus placebo was Euros 4074/LYG and Euros 2486/LYG (discounted at 5% per annum
      and in 1998-2002 values; Euro 1 approximately USD 0.88; first quarter 2002
      values) for the HOPE study population as a whole and the subgroup of patients
      with diabetes, respectively. To test the model's robustness, the influence of the
      model variables on the results was quantified using a deterministic model, and a
      best-case/worst-case scenario analysis. The effect of random variables was
      investigated in a Monte Carlo simulation. The acquisition cost for ramipril had
      the greatest impact on the ICER of ramipril (2.2-fold greater than the impact of
      the number of LYG). In 95% of the 10,000 simulation steps, the ICER of ramipril
      after 4.5 years of treatment was between Euros 1290 and Euros 9005 per LYG for
      the entire HOPE study population and between Euros 290 and Euros 6115 per LYG in
      the diabetic subgroup. CONCLUSIONS: Results of this evaluation suggest that
      ramipril is likely to be cost effective in secondary prevention of cardiovascular
      events from the perspective of the SHI (third-party payer) in Germany. The
      estimated ICER of ramipril compares well with other ICERs of widely accepted
      treatments used for the management of cardiovascular diseases, such as HMG-CoA
      reductase inhibitors.

PMID- 15449962
TI  - Does seropositivity for Helicobacter pylori antibodies increase outpatient costs
      for gastric and duodenal ulcer or inflammation?
AB  - BACKGROUND: Helicobacter pylori is regarded as an important cause of both peptic
      ulcer and chronic gastritis. In particular, seropositivity is highest in patients
      with duodenal ulcer. No studies have determined whether there are differences in
      the direct medical costs associated with gastric/duodenal ulcer or inflammation,
      between seropositive and seronegative patients. OBJECTIVE: To examine the
      relationship between seropositivity for H. pylori and outpatient visits and
      direct medical costs for gastric/duodenal ulcer or inflammation in Japan from the
      perspective of the payor and patients. METHODS: Participants were males (n = 653)
      who worked for an agricultural co-operative in Fukuoka Prefecture, attended an
      annual health examination (including a written lifestyle and medical survey),
      belonged to the same health insurance society consistently for 4 years from April
      1996 to March 2000, and provided a blood sample. The survey asked about
      lifestyle, including smoking and drinking, and past medical history. We
      retrospectively analysed the annual number of outpatient visits per person and
      outpatient medical cost (Yen, 2000 values) per person for visits relating to
      gastric or duodenal ulcer or inflammation using International Classification of
      Diseases (9th edition) -- Clinical Modification codes. We assessed for potential
      confounding factors using analysis of covariance and the chi-square test.
      RESULTS: The annual outpatient incidence of disease, the number of visits to
      physicians, and the medical costs for gastric or duodenal ulcer or inflammation
      were about 2-fold greater in individuals with antibodies to H. pylori compared
      with those without antibodies. CONCLUSION: Population-based studies and/or
      randomised controlled clinical trials that target high-risk groups and account
      for the unique way in which data are collected in Japan are needed to determine
      whether medical costs for gastric and duodenal ulcer might be reduced by treating
      asymptomatic patients who have antibodies to H. pylori.

PMID- 15449963
TI  - Economic impact of migraine and other episodic headaches in France: data from the
      GRIM2000 study.
AB  - BACKGROUND: Migraine is a prevalent and incapacitating condition that affects
      individuals in the prime of their productive life, thus generating an economic
      burden for both society and healthcare systems. The direct annual healthcare
      costs of migraine in France were assessed over 10 years ago, and the current
      study updates these figures. OBJECTIVE: The objective of this study was to
      determine the economic cost (primarily direct costs) of migraine and other
      episodic headache in France based on a general population survey of headache, the
      GRIM2000 (Groupe de Researche Interdisciplinaire sur la Migraine). DESIGN: From a
      representative general population sample of 10,585 individuals aged > or = 15
      years in France in 1999, 1486 individuals experiencing headaches were identified
      and interviewed regarding healthcare resource consumption in the previous 6
      months. By applying unit costs to the resource data, costings (in 1999 values)
      were determined for physician consultations, hospitalisation, medication use and
      diagnostic/laboratory tests, and evaluated from a healthcare system perspective.
      Information on absenteeism and lost productivity was derived from the Migraine
      Disability Assessment Score (MIDAS) questionnaire. RESULTS: The prevalence of
      migraine (including migrainous disorder) was determined to be 17%. Total annual
      direct healthcare costs were estimated to be Euros 128 per individual with
      migraine in 1999, corresponding to Euros 1044 million when extrapolated to all
      individuals experiencing migraine and aged > or = 15 years. Around two-thirds of
      this cost accrued to the social security system (Euros 698 million; Euros 85 per
      individual). The total annual direct cost of other forms of episodic headache was
      much lower at Euros 28 per individual (social security cost Euros 18); with a
      prevalence of 9.2%, the annual national direct cost for other forms of episodic
      headache totalled Euros 124 million. The principal cost element was physician
      consultations. However, it was found that many individuals had never consulted a
      physician for their headaches, and self-medication contributed substantially to
      the medication costs (the second greatest cost factor for migraine). The cost per
      individual rose steeply with increasing severity of headache. CONCLUSIONS: The
      direct healthcare costs of migraine do not seem to have risen significantly over
      the past decade. A small minority of individuals with more severe headaches
      consume most of the healthcare resources devoted to migraine, while most
      individuals generate relatively low direct costs. The total annual direct costs
      in France for migraine are almost 10-fold higher than those of other episodic
      headache.

PMID- 15449964
TI  - Comparisons of hypertension-related costs from multinational clinical studies.
AB  - BACKGROUND: This study identifies and compares the individual cost components of
      hospital and ambulatory services that manage the care of hypertensive patients in
      eight countries: the US, the UK, France, Spain, Germany, Italy, Canada and
      Australia. METHODS: Hypertension-related costs are classified according to four
      major cardiovascular events: (i) acute myocardial infarction; (ii) congestive
      heart failure; (iii) stroke; and (iv) renal failure, which was subdivided into
      renal failure treated by dialysis and renal failure treated by kidney
      transplantation. To make cross-country costs comparisons, we used the DRG codes
      used in the US and DRG-like codes from each country. US cost information was
      obtained from hypertension data available from the literature and health
      economics researchers. For costs in other countries, we consulted with national
      health economics experts in each country, used analyses by the Research Triangle
      Institute, and performed Medline and international literature searches. When
      available, we obtained information from the countries' public and private
      nationally representative data sources. For cross-country currency adjustments,
      all currencies were converted using the Purchasing Power Parities from the
      Organisation for Economic Cooperation and Development, and then converted into
      inflation-adjusted year 2000 US dollars. RESULTS: There exists considerable
      variation in hypertension-related costs from multinational clinical studies. This
      study documents that costs are generally higher in the US than in other
      countries; however, this is not always true. In particular, costs of treating
      heart failure in France and the costs of renal failure without transplantation in
      Germany and the UK are relatively high. DISCUSSION: While analysing multinational
      hypertensive cost data, this study also addresses the impact of cross-country
      cost variations on cost analyses. During the last decade, drug-development
      researchers have drawn extensively upon multinational trials to resolve
      enrollment problems and drug-registration issues. At the same time, formulary
      decision-makers are increasingly demanding multinational cost-effectiveness
      analyses of the clinical differences found between drug-treatment regimens. Since
      these data are typically not captured by randomised clinical trials, standard
      cost estimates must be applied to the clinical trials' resource data, although
      such standardised calculations do not necessarily account for clinical and cost
      variations between countries. CONCLUSION: This paper serves as an instrument for
      identifying which national and event cost data are comparable for analysis as
      well as highlighting specific problem areas for cost data integration. Although
      the study focuses on hypertension-related costs, its results may provide insight
      for multinational cost comparisons of other diseases where similar
      hospitalisation costs may be analysed.

PMID- 15449965
TI  - Cost effectiveness of ACE inhibitor treatment for patients with type 1 diabetes
      mellitus.
AB  - OBJECTIVE: Current guidelines recommend treating patients with type 1 diabetes
      mellitus with ACE inhibitors after the onset of microalbuminuria. Recent clinical
      trials have shown ACE inhibitors can affect the development of nephropathy when
      initiated prior to the onset of microalbuminuria. Our objective is to examine the
      cost effectiveness of treating adults aged over 20 years with an ACE inhibitor
      (captopril) immediately following diagnosis of type 1 diabetes versus treating
      them after the onset of microalbuminuria. DESIGN: Using a semi-Markov model, we
      calculated four main outcome measures: lifetime direct medical costs
      (discounted), QALYs, cumulative incidence of end-stage renal disease (ESRD), and
      number of days of ESRD over a lifetime. Medical costs are in 1999 US dollars.
      SETTING: All analyses were from the viewpoint of a single US payer responsible
      for all direct medical costs, including screening for microalbuminuria, ACE
      inhibitor treatment (captopril), management of major diabetic complications, and
      routine annual medical costs not specific to diabetes. METHODS: We applied the
      model to a hypothetical cohort of 10,000 persons newly diagnosed with type 1
      diabetes. Distribution of sex and race/ethnicity within the cohort is
      representative of the general US population. RESULTS: We estimated that the
      incremental cost of early use of captopril for the average adult with type 1
      diabetes is USD 27,143 per QALY. This level varies considerably with age and
      glycaemic level. When the age at onset of diabetes is 20 years and glycosylated
      haemoglobin (HbA(1c)) level is 9%, the cost-effectiveness ratio is USD 13,814 per
      QALY. When the age at onset is 25 years and HbA(1c) level is 7%, the cost
      effectiveness ratio is USD 39,530 per QALY. CONCLUSION: This model, with its
      underlying assumptions and data, suggests that early treatment with captopril
      provides modest benefit at reasonable cost effectiveness, from the US single
      payer perspective, in the prevention of ESRD compared with delaying treatment
      until diagnosis of microalbuminuria. Early treatment with other ACE inhibitors
      will provide similar cost effectiveness if they have equivalent efficacy,
      compliance and price per dose. Treatment may be considered among patients at age
      20 years with new onset of type 1 diabetes. This conclusion is sensitive to the
      extent that ACE inhibitors delay onset of microalbuminuria. Other factors such as
      the patient's age and glycaemic level must be considered when deciding to
      initiate early treatment.

PMID- 15449966
TI  - Ibuprofen and increased morbidity in children with asthma: fact or fiction?
AB  - NSAIDs are commonly avoided by patients with aspirin-induced asthma based on the
      premise that there is a significant cross-reactivity between aspirin and other
      NSAIDs. However, ibuprofen, a NSAID sold over the counter in most countries, is
      commonly given to children for relief of fever and mild-to-moderate pain.
      Consequently, increased risk of acute bronchospasm induced by ibuprofen in
      children with asthma remains a persistent concern. More recently, the assumption
      that children with asthma are at a greater risk for exacerbations of their
      disease if they take ibuprofen has been questioned. There is little evidence to
      measurably increases morbidity in the great majority of children with asthma. In
      addition, recent evidence suggest that ibuprofen measurably increases morbidity
      in the great majority of [corrected] children with asthma. Given the infrequent
      occurrence of aspirin/NSAID sensitivity in children with asthma, it seems
      reasonable to allow the use of ibuprofen in this population unless there is a
      personal or family history of aspirin-induced asthma. In addition, the
      inflammatory pathogenesis of asthma, anti-inflammatory effect of ibuprofen, and
      evidence suggesting ibuprofen may reduce morbidity in children with asthma raises
      the intriguing possibility that ibuprofen might actually have therapeutic benefit
      for at least some children with asthma.

PMID- 15449967
TI  - Corticosteroid avoidance in pediatric renal transplantation: can it be achieved?
AB  - Corticosteroids have been a cornerstone therapy in renal transplantation, which
      is the treatment modality of choice for adult and pediatric end-stage renal
      disease. Their use is associated with significant morbidity, notably
      cardiovascular, endocrine, and bone complications, body disfiguration, and almost
      universal growth retardation in children. While newer immunosuppressants have
      reduced the incidence of these adverse effects, they continue to pose significant
      post-transplant challenges. There are various strategies that can be used to
      avoid these adverse effects including the use of an alternative corticosteroid
      such as deflazacort, minimization of corticosteroid dosage, corticosteroid
      withdrawal after a period of early use, and more recently complete corticosteroid
      avoidance. Recent randomized studies have demonstrated significant improvement in
      growth parameters, lipid profile, and in the amount of bone loss in patients
      treated with deflazacort, an oxazoline analog of prednisone, compared with
      methylprednisone.Corticosteroid minimization has been associated with an
      increased rate of acute rejection. While augmentation with newer
      immunosuppressants has helped reduce the incidence of acute rejection,
      significant improvements in growth have not been demonstrated. Alternate-day
      corticosteroid therapy has been shown to have a beneficial effect on growth but
      regimen compliance has limited its widespread applicability. Studies of
      corticosteroid withdrawal have met with varied success. Early corticosteroid
      withdrawal has been associated with rejection rates ranging from 10% to 81% and
      late corticosteroid withdrawal, from 13% to 68.8%, with acute rejection episodes
      occurring as late as 4 years after corticosteroid withdrawal. The rates of
      clinical acute rejection have been unacceptably high, and corticosteroid
      withdrawal is thus used very sparingly in adults and even less so in children.
      Complete corticosteroid avoidance as reported by an initial study has been
      associated with a 23% incidence of acute rejection and 'catch-up' growth post
      transplantation in 14 pediatric recipients, as measured by the change in height
      standard deviation scores post-transplantation. A second renal transplant study,
      in adults, demonstrated similar rejection rates of 25% with improvement in post
      transplant hypertension and lipid profiles. A more recent pediatric study using a
      novel extended daclizumab induction protocol demonstrated an 8% incidence of
      clinical acute rejection with significant improvements in graft function,
      hypertension, and growth, without an increased incidence of infectious
      complications. Renal transplantation with a corticosteroid-free protocol may
      offer significant advantages in the incidence of acute rejection, graft function,
      growth, blood pressure, lipidemia, and body appearance and appears to be well
      tolerated when used with a variety of current induction protocols to replace
      early corticosteroid use. This protocol may also be applicable to other areas of
      solid organ transplantation in all age groups.

PMID- 15449968
TI  - Treatment of ocular inflammation in children.
AB  - Ocular inflammation in children is of substantial epidemiologic importance,
      particularly since uveitis in children produces more vision loss than it does in
      adults. This is partially because there is a higher rate of posterior uveitis in
      childhood uveitis than in the adult population. Treatment of ocular inflammation
      in children, ranging from conjunctivitis to keratitis to scleritis to uveitis,
      depends, of course, on whether or not the problem is microbial, traumatic,
      malignant, or autoimmune. Most of the cases that are vision threatening are
      autoimmune, and corticosteroids represent the mainstay of short-term therapy.
      However, abundant evidence exists which shows that all too often imprudent,
      prolonged use of corticosteroids is employed with resultant iatrogenic damage,
      including cataract, glaucoma, and secondary infection.A new paradigm for treating
      ocular inflammation (uveitis in particular) is espoused in this article. It is
      based on a limited tolerance to corticosteroid use and a more proactive approach
      to corticosteroid-sparing immunomodulatory therapy in an effort to induce a
      durable remission off all corticosteroids.

PMID- 15449970
TI  - Impaired glucose metabolism in patients with heart failure: pathophysiology and
      possible treatment strategies.
AB  - The firm association of diabetes mellitus with congestive heart failure (CHF) has
      been undoubtedly established. Recent reports support the presence of the
      reciprocal interrelationships between CHF and glucose abnormalities. The present
      review provides an overview of some aspects of the multifactorial
      interrelationships between heart failure and diabetes mellitus. Patients with
      heart failure are generally at higher risk of developing type 2 diabetes
      mellitus. Several factors may be involved, such as a lack of physical activity,
      hypermetabolic state, intracellular metabolic defects, poor muscle perfusion, and
      poor nutrition. Serum levels of inflammatory cytokines and leptin are elevated in
      patients with heart failure. Activation of the sympathetic system in CHF not only
      increases insulin resistance but also decreases the release of insulin from the
      pancreatic beta cells, increases hepatic glucose production by stimulating both
      gluconeogenesis and glycogenolysis, and increases glucagon production and
      lipolysis. People who develop type 2 diabetes mellitus usually pass through the
      phases of nuclear peroxisome proliferator-activated receptor modulation, insulin
      resistance, hyperinsulinemia, pancreatic beta-cell stress and damage leading to
      progressively decreasing insulin secretion, and impaired fasting and postprandial
      blood glucose levels. Once hyperglycemia ensues, the risk of metabolic and
      cardiovascular complications also increases. It is possible that the cornerstone
      of diabetes mellitus prevention in patients with CHF could be controlled by
      increased physical activity in a cardiac rehabilitation framework. Pharmacologic
      interventions by some medications (metformin, orlistat, ramipril and acarbose)
      can also effectively delay progression to type 2 diabetes mellitus in general
      high risk populations, but the magnitude of the benefit in patients with CHF is
      unknown. In patients with CHF and overt diabetes mellitus, ACE inhibitors may
      provide a special advantage and should be the first-line agent. Recent reports
      have suggested that angiotensin receptor antagonists (angiotensin receptor
      blockers), similar to ACE inhibitors, provide beneficial effects in patients with
      diabetes mellitus and should be the second-line agent if ACE inhibitors are
      contraindicated. Treatment with HMG-CoA reductase inhibitors should probably now
      be considered routinely for all diabetic patients with CHF, irrespective of their
      initial serum cholesterol levels, unless there is a contraindication.

PMID- 15449971
TI  - Interactions between grapefruit juice and cardiovascular drugs.
AB  - Grapefruit juice can alter oral drug pharmacokinetics by different mechanisms.
      Irreversible inactivation of intestinal cytochrome P450 (CYP) 3A4 is produced by
      commercial grapefruit juice given as a single normal amount (e.g. 200-300 mL) or
      by whole fresh fruit segments. As a result, presystemic metabolism is reduced and
      oral drug bioavailability increased. Enhanced oral drug bioavailability can occur
      24 hours after juice consumption. Inhibition of P-glycoprotein (P-gp) is a
      possible mechanism that increases oral drug bioavailability by reducing
      intestinal and/or hepatic efflux transport. Recently, inhibition of organic anion
      transporting polypeptides by grapefruit juice was observed in vitro; intestinal
      uptake transport appeared decreased as oral drug bioavailability was reduced.
      Numerous medications used in the prevention or treatment of coronary artery
      disease and its complications have been observed or are predicted to interact
      with grapefruit juice. Such interactions may increase the risk of rhabdomyolysis
      when dyslipidemia is treated with the HMG-CoA reductase inhibitors atorvastatin,
      lovastatin, or simvastatin. Potential alternative agents are pravastatin,
      fluvastatin, or rosuvastatin. Such interactions might also cause excessive
      vasodilatation when hypertension is managed with the dihydropyridines felodipine,
      nicardipine, nifedipine, nisoldipine, or nitrendipine. An alternative agent could
      be amlodipine. In contrast, the therapeutic effect of the angiotensin II type 1
      receptor antagonist losartan may be reduced by grapefruit juice. Grapefruit juice
      interacting with the antidiabetic agent repaglinide may cause hypoglycemia, and
      interaction with the appetite suppressant sibutramine may cause elevated BP and
      HR. In angina pectoris, administration of grapefruit juice could result in
      atrioventricular conduction disorders with verapamil or attenuated antiplatelet
      activity with clopidrogel. Grapefruit juice may enhance drug toxicity for
      antiarrhythmic agents such as amiodarone, quinidine, disopyramide, or
      propafenone, and for the congestive heart failure drug, carvediol. Some drugs for
      the treatment of peripheral or central vascular disease also have the potential
      to interact with grapefruit juice. Interaction with sildenafil, tadalafil, or
      vardenafil for erectile dysfunction, may cause serious systemic vasodilatation
      especially when combined with a nitrate. Interaction between ergotamine for
      migraine and grapefruit juice may cause gangrene or stroke. In stroke,
      interaction with nimodipine may cause systemic hypotension. If a drug has low
      inherent oral bioavailability from presystemic metabolism by CYP3A4 or efflux
      transport by P-gp and the potential to produce serious overdose toxicity,
      avoidance of grapefruit juice entirely during pharmacotherapy appears mandatory.
      Although altered drug response is variable among individuals, the outcome is
      difficult to predict and avoiding the combination will guarantee toxicity is
      prevented. The elderly are at particular risk, as they are often prescribed
      medications and frequently consume grapefruit juice.

PMID- 15449972
TI  - Significance of high density lipoprotein-cholesterol in cardiovascular risk
      prevention: recommendations of the HDL Forum.
AB  - In the approach to lipid-related risk factors for cardiovascular diseases, serum
      high density lipoprotein-cholesterol (HDL-C) levels bear a particular
      significance as this lipoprotein is considered to be an antiatherogenic factor
      mainly, but not only, because of its influence and impact on reverse cholesterol
      transport. Hence the need and requirement to consider serum HDL-C levels for both
      primary and secondary prevention of cardiovascular disease. A particularly
      important aspect is the association of the 'low HDL syndrome' with the metabolic
      syndrome. These factors force us to consider serum HDL-C level as a therapeutic
      target by itself, or even in association with low density lipoprotein-cholesterol
      (LDL-C) levels when the latter are increased. This review stresses the aspects
      connecting serum HDL-C levels and cardiovascular risk, and looks at the
      populations that should be considered amenable to therapeutic management because
      of low serum HDL-C levels. We review therapeutic strategies, both pharmacological
      and nonpharmacological. The aim of this review is to present therapeutic
      management recommendations for correcting the proportion of cardiovascular risk
      that is attributable to changes in HDL-C. Serum HDL-C levels of >40 mg/dL must be
      a therapeutic target in primary and secondary prevention. This goal is
      particularly important in patients with low serum HDL-C levels and ischemic heart
      disease (IHD) or its equivalents, even if the therapeutic target for serum LDL-C
      levels (<100 mg/dL) has been achieved. The first choice for this clinical
      condition is fibric acid derivates. The same therapeutic option should be
      considered in patients without IHD with low serum HDL-C levels and high
      cardiovascular risk (>20%), hypertriglyceridemia, type 2 diabetes mellitus, or
      metabolic syndrome.

PMID- 15449969
TI  - Bronchopulmonary dysplasia in preterm infants: pathophysiology and management
      strategies.
AB  - Bronchopulmonary dysplasia (BPD) has classically been described as including
      inflammation, architectural disruption, fibrosis, and disordered/delayed
      development of the infant lung. As infants born at progressively earlier
      gestations have begun to survive the neonatal period, a 'new' BPD, consisting
      primarily of disordered/delayed development, has emerged. BPD causes not only
      significant complications in the newborn period, but is associated with
      continuing mortality, cardiopulmonary dysfunction, re-hospitalization, growth
      failure, and poor neurodevelopmental outcome after hospital discharge. Four major
      risk factors for BPD include premature birth, respiratory failure, oxygen
      supplementation, and mechanical ventilation, although it is unclear whether any
      of these factors is absolutely necessary for development of the condition.
      Genetic susceptibility, infection, and patent ductus arteriosus have also been
      implicated in the pathogenesis of the disease. The strategies with the strongest
      evidence for effectiveness in preventing or lessening the severity of BPD include
      prevention of prematurity and closure of a clinically significant patent ductus
      arteriosus. Some evidence of effectiveness also exists for single-course therapy
      with antenatal glucocorticoids in women at risk for delivering premature infants,
      surfactant replacement therapy in intubated infants with respiratory distress
      syndrome, retinol (vitamin A) therapy, and modes of respiratory support designed
      to minimize 'volutrauma' and oxygen toxicity. The most effective treatments for
      ameliorating symptoms or preventing exacerbation in established BPD include
      oxygen therapy, inhaled glucocorticoid therapy, and vaccination against
      respiratory pathogens.Many other strategies for the prevention or treatment of
      BPD have been proposed, but have weaker or conflicting evidence of effectiveness.
      In addition, many therapies have significant side effects, including the
      possibility of worsening the disease despite symptom improvement. For instance,
      supraphysiologic systemic doses of glucocorticoids lessen the incidence of BPD in
      infants at risk for the disease, and promote weaning of oxygen and mechanical
      ventilation in infants with established BPD. However, the side effects of
      systemic glucocorticoid therapy, most notably the recently recognized adverse
      effects on neurodevelopment, preclude their routine use for the prevention or
      treatment of BPD. Future research in BPD will most probably focus on continued
      incremental improvements in outcome, which are likely to be achieved through the
      combined effects of many therapeutic modalities.

PMID- 15449973
TI  - HIV-related cardiovascular disease and drug interactions.
AB  - HIV infection is a global public health issue that is frequently associated with
      cardiovascular involvement. These HIV-associated cardiovascular manifestations
      are often clinically occult or attributed incorrectly to other non-cardiac
      disease processes. A heightened awareness and routine screening for
      cardiovascular involvement in HIV-infected patients leads to earlier detection
      and the hope for a reduction in associated morbidity and mortality. Left
      ventricular dysfunction, an independent predictor of mortality in HIV-infected
      patients, is the result of many causes in this population and may result in
      dilated cardiomyopathy and congestive heart failure in about 10% of patients.
      Other HIV-associated cardiovascular problems include infective endocarditis,
      cardiovascular malignancy, pulmonary arterial hypertension, vasculitis,
      pericardial effusion, premature atherosclerosis, and arrhythmias. HIV-associated
      cardiovascular emergencies include congestive heart failure, pulmonary edema,
      supraventricular and ventricular arrhythmias, endocarditis, and tamponade. Anti
      infective and immunomodulatory therapies may be particularly helpful in this
      population to reduce associated cardiovascular disease. Highly active
      antiretroviral therapy may result in lipodystrophy, hyperlipidemia, truncal
      adiposity, and insulin resistance that can be improved by physical activity and
      training programs. Cardiovascular complications of therapeutic drugs in HIV
      infected patients include torsade de pointes, congestive heart failure,
      dyslipidemia, accelerated atherosclerosis, and myocardial infarction. In summary,
      cardiovascular complications are important contributors to morbidity and
      mortality in HIV-infected patients that can be detected early in many cases and
      treated effectively.

PMID- 15449974
TI  - Pharmacoeconomic analysis of fondaparinux versus enoxaparin for the prevention of
      thromboembolic events in orthopedic surgery patients.
AB  - INTRODUCTION: Fondaparinux is a novel synthetic antithrombotic that has been
      evaluated for the prevention of venous thromboembolism (VTE). In four large
      trials in patients who underwent major hip or knee surgery, fondaparinux was
      found to have a good safety profile and be more effective than enoxaparin. To
      generate Canadian pharmacoeconomic data for fondaparinux, an internationally
      developed cohort deterministic model was used to estimate the costs and
      consequences of prophylaxis with fondaparinux compared with enoxaparin in the
      Canadian orthopedic surgical setting. DESIGN AND SETTING: A health economic
      advisory group was assembled to guide the pharmacoeconomic evaluation. Efficacy
      and safety data for fondaparinux relative to enoxaparin were abstracted from a
      meta-analysis of four randomized trials. Canadian cost data to populate the model
      were obtained from a resource-use survey of four large Canadian hospitals, from
      the Canadian Institute for Health Information (CIHI), and from the Canadian
      economic literature. Case-mix information obtained from CIHI was incorporated
      into the cohort deterministic model, which predicted the number of VTEs and
      bleeds following prophylaxis with fondaparinux or enoxaparin within 90 days of
      surgery, and the associated overall cost difference. The stability of the base
      case findings was evaluated with sensitivity analyses. STUDY PERSPECTIVE:
      Canadian healthcare system perspective. MAIN OUTCOME MEASURES AND RESULTS:
      Assuming a case mix of 50,693 major hip or knee surgeries performed in Canada in
      1999/2000 (as reported by CIHI), the model predicted that prophylaxis with
      fondaparinux would avoid an additional 16 symptomatic VTEs per 1000 patients over
      the first 90 days, with an average cost savings of Can 55 dollars per patient.
      These findings were stable when key economic and clinical parameters were varied,
      including bleeding events. CONCLUSIONS: Our results suggest that in Canada,
      prophylactic fondaparinux compared with enoxaparin avoids VTEs and is associated
      with lower costs in patients who undergo major hip or knee surgery.

PMID- 15449975
TI  - Clinical experience with perindopril in elderly hypertensive patients: a subgroup
      analysis of a large community trial.
AB  - OBJECTIVE: To evaluate the effectiveness and safety of perindopril in a subgroup
      of 3010 elderly (> or =65 years) hypertensive patients, who participated in a
      large US general practice-based community trial. METHODS: All patients received
      open-label perindopril 4 mg once a day for 6 weeks. After 6 weeks the dosage was
      either maintained (group I) or increased to 8 mg/day (group II) based on the
      physician's assessment of blood pressure (BP) response. Patients were then
      followed for another 6 weeks for a total study duration of 12 weeks. RESULTS:
      Demographic and baseline clinical characteristics revealed a higher proportion of
      women, longer duration of hypertension and higher baseline systolic BP (SBP)
      among elderly than young (<65 years, n = 7332) hypertensive patients. A
      clinically relevant BP reduction of similar magnitude was obtained in elderly and
      young patients with perindopril monotherapy. At week 12, the mean reduction in BP
      from baseline was 18.4/8.7 mm Hg in the elderly and 17.5/11.3 mm Hg in the young.
      Elderly patients with hypertension not responding adequately to the 4 mg/day
      dosage at week 6 had a BP reduction of 6.3/3.6 mm Hg (group II). Up-titration to
      an 8 mg/day dosage for another 6 weeks gave an additional 8.9/3.5 mm Hg reduction
      resulting in a total reduction of 15.2/7.1 mm Hg from baseline. A similar
      magnitude of increase in response to up-titration of perindopril was seen in
      young patients. BP control (<140/90 mm Hg) on perindopril monotherapy was
      achieved in 41.4% of elderly and 51.9% of young patients. In both age groups, up
      titration to an 8.0 mg/day dosage in group II patients increased BP control by
      approximately 5-fold at week 12 (28.2% in the elderly and 36.4% in the young). A
      similar increased response on BP reduction and BP control (<140/90 mm Hg) with up
      titration was seen in elderly subgroups of African American and diabetic
      patients. The 7th Report of the Joint National Committee on Prevention,
      Detection, Evaluation and Treatment of High Blood Pressure recommended target
      goal of <130/80 mm Hg was achieved with perindopril monotherapy in 15.6% of
      hypertensive diabetic patients. Perindopril reduced BP effectively and safely in
      very elderly (> or =75 years) hypertensive patients. Perindopril was well
      tolerated in elderly patients including high-risk groups. The incidence of cough
      (7-10%), the most common symptom, was similar in all age groups. The low
      incidence of postural hypotension (< or =0.2%) observed in the elderly and very
      elderly further supports the good tolerance and safety profile of the drug. Data
      analysis from this study suggests that community physicians, in general, are less
      aggressive in controlling BP in the elderly and more inclined to treat or control
      diastolic BP than SBP. CONCLUSION: Perindopril treatment is effective and well
      tolerated in elderly patients with hypertension.

PMID- 15449976
TI  - Reliability, internal consistency, and validity of data obtained with the
      functional gait assessment.
AB  - BACKGROUND AND PURPOSE: The Functional Gait Assessment (FGA) is a 10-item gait
      assessment based on the Dynamic Gait Index. The purpose of this study was to
      evaluate the reliability, internal consistency, and validity of data obtained
      with the FGA when used with people with vestibular disorders. SUBJECTS: Seven
      physical therapists from various practice settings, 3 physical therapist
      students, and 6 patients with vestibular disorders volunteered to participate.
      METHODS: All raters were given 10 minutes to review the instructions, the test
      items, and the grading criteria for the FGA. The 10 raters concurrently rated the
      performance of the 6 patients on the FGA. Patients completed the FGA twice, with
      an hour's rest between sessions. Reliability of total FGA scores was assessed
      using intraclass correlation coefficients (2,1). Internal consistency of the FGA
      was assessed using the Cronbach alpha and confirmatory factor analysis.
      Concurrent validity was assessed using the correlation of the FGA scores with
      balance and gait measurements. RESULTS: Intraclass correlation coefficients of.86
      and.74 were found for interrater and intrarater reliability of the total FGA
      scores. Internal consistency of the FGA scores was.79. Spearman rank order
      correlation coefficients of the FGA scores with balance measurements ranged
      from.11 to.67. DISCUSSION AND CONCLUSION: The FGA demonstrates what we believe is
      acceptable reliability, internal consistency, and concurrent validity with other
      balance measures used for patients with vestibular disorders.

PMID- 15449977
TI  - Decision making for physical therapy service delivery in schools: a nationwide
      survey of pediatric physical therapists.
AB  - BACKGROUND AND PURPOSE: A nationwide survey was conducted to explore decision
      making among school-based physical therapists and to examine recommendations
      regarding the models, contexts, frequency, and intensity of physical therapy
      service delivery. Factors that the therapists considered important in making
      clinical decisions also were examined. SUBJECTS AND METHODS: A survey instrument
      using a clinical case format was sent to all members of the American Physical
      Therapy Association's Section on Pediatrics who identified themselves as school
      based therapists (N=1,154); 626 respondents, from all 50 states, completed the
      survey. Four case descriptions were presented in the survey: 2 preschool girls
      with developmental delay (1 with and 1 without cognitive impairment) and a boy
      with cerebral palsy (at 6 and 12 years of age). RESULTS: Individual direct
      services were recommended by 52% to 55% of the respondents for both 4-year-old
      girls and for the boy at 12 years of age; 92% of the respondents recommended them
      for the boy at 6 years of age. The most prevalent choice (48%-73%) for the
      context of service delivery (location or environment) was a combination of
      integrated and isolated contexts. For those respondents who selected direct
      services (individual or group, or both), the mean recommended monthly frequency
      for the boy at 6 years of age (5.8) was more than twice that for the boy at 12
      years of age (2.4). The mean suggested direct frequency for the girl with
      cognitive impairment (4.5) was greater than that for the girl without cognitive
      impairment (4). The students' functional levels were considered very to extremely
      important in decision making by 87% to 90% of the respondents. DISCUSSION AND
      CONCLUSION: Survey responses were relatively consistent with current literature
      regarding school practice and principles of motor learning. Recommendations
      varied for each case, regarding the models, contexts, frequency, and intensity of
      physical therapy service delivery.

PMID- 15449978
TI  - Ottawa Panel evidence-based clinical practice guidelines for therapeutic
      exercises in the management of rheumatoid arthritis in adults.
AB  - BACKGROUND AND PURPOSE: The purpose of this project was to create guidelines for
      the use of therapeutic exercises and manual therapy in the management of adult
      patients (>18 years of age) with a diagnosis of rheumatoid arthritis according to
      the 1987 American Rheumatism Association criteria. METHODS: Evidence from
      comparative controlled trials was identified and synthesized using The Cochrane
      Collaboration methods. An expert panel was formed by inviting professional
      stakeholder organizations to each nominate a representative. This panel developed
      a set of criteria for grading the strength of both the evidence and the
      recommendation. RESULTS: Six positive recommendations of clinical benefit were
      developed on therapeutic exercises. The efficacy of manual therapy interventions
      could not be determined for lack of evidence. DISCUSSION AND CONCLUSION: The
      panel recommends the use of therapeutic exercises for rheumatoid arthritis.
      Further research is needed to determine the efficacy of manual therapy in the
      management of this disease.

PMID- 15449979
TI  - Pharmacologic management of spasticity following stroke.

PMID- 15449980
TI  - Ultrasound efficacy.

PMID- 15449981
TI  - Ultrasound efficacy.

PMID- 15449982
TI  - Ultrasound efficacy.

PMID- 15449983
TI  - Role of the peritoneum in the pathogenesis of acute pancreatitis-associated lung
      injury.

PMID- 15449984
TI  - Pulmonary injuries and cytokine levels after the intraperitoneal administration
      of pancreatic homogenates in rats.
AB  - INTRODUCTION: Our objective was to investigate the effects of the administration
      of pancreatic homogenates, with or without enzymatic activation, to healthy
      animals regarding cytokine serum levels and the development of pulmonary
      distress. MATERIAL AND METHODS: 106 male Wistar rats, divided into three groups,
      were studied: group A, intraperitoneal administration of homogenates activated
      with enterokinase; group B, homogenates without enterokinase; and group C,
      control group with administration of physiological saline solution. Each group
      was divided into 4 subgroups according to the time of sacrifice: 0, 2, 6 and 24
      hours. We studied the pulmonary and pancreatic histology, serum parameters of
      renal and hepatic function, and serum levels of IL-1beta, IL-6 and TNFalpha.
      RESULTS: There was no mortality in any group. Pancreatic disorders in A and B
      groups were noted at 24 hours. These two groups had statistically significant
      higher transaminase serum levels than those of the control group, as well as
      statistically significant higher creatinine levels in group A. IL-1beta showed a
      statistically significant higher level at 6 h in both groups, A and B, but was
      higher in group A, which also exhibited significant pulmonary histologic damage
      with respect to controls at 6 h. CONCLUSIONS: The higher IL-1beta level in group
      A may result from production by peritoneal macrophages under the influence of
      homogenate enzymatic activation. This may be the reason for lung damage.

PMID- 15449985
TI  - Response of first attack of inflammatory bowel disease requiring hospital
      admission to steroid therapy.
AB  - INTRODUCTION: Corticoid administration is the usual treatment of Crohns disease
      (CD) and ulcerative colitis (UC) attacks. However, information available on
      response rates and their predictive factors is scarce. OBJECTIVE: To establish
      response to steroidal treatment in an homogeneous group of patients with CD or UC
      during their first admission to hospital. METHODS: Restrospective analysis of 86
      patients who received systemic steroidal treatment for a severe flare-up during
      their first hospital admission between 1995 and 2000. Patients were treated per
      protocol with fluid therapy, absolute diet, IV 6-methyl-prednisolone 1 mg/kg/day,
      and enoxaparin at prophylactic doses. Clinical response at 30 days was considered
      good in case of complete remission, and poor in case of partial or absent
      remission. Univariate and multivariate analyses according to non-parametric
      statistics were performed for sociodemographic and biologic variables. RESULTS:
      45 patients with CD and 41 with UC were included. Good response rates were 64.4%
      for CD and 60.9% for UC. The univariate analysis showed that patients with good
      response have shorter evolution times and fewer previous flare-ups (p < 0.05)
      regarding CD. However, the multivariate analysis showed that none of the analyzed
      variables had predictive value. CONCLUSION: The response rate of severe
      inflammatory bowel disease attacks to corticoids is around 60% in CD and UC. Data
      resulting from the current study cannot predict which patients will ultimately
      respond to therapy.

PMID- 15449986
TI  - Retreatment and maintenance therapy with infliximab in fistulizing Crohn's
      disease.
AB  - OBJECTIVES: Infliximab has clearly demonstrated its efficacy in the short-term
      treatment of fistulizing Crohn's disease. We present here the results of
      retreatment and long-term maintenance therapy. PATIENTS AND METHODS: Eighty one
      consecutive patients with active fistulizing Crohn's disease, in whom previous
      treatments had failed, were treated with infliximab. All patients received as the
      initial treatment of 5 mg/kg i.v. infusions (weeks 0, 2, and 6). Those patients
      who failed to respond after the initial cycle (group 1, n = 25), or those who
      relapsed after having responded (group 2, n = 13), received retreatment with
      three similar doses (weeks 0,2, and 6). Those who responded to retreatment were
      included in a long-term maintenance programme (n = 44), with repeated doses (5
      mg/kg i.v. infusions) every eight weeks for 1-2 years. RESULTS: In the initial
      treatment 56% of the patients responded partially; this response being complete
      in 44%. In the retreatment, 28% of group 1 (non-responders) presented a complete
      response, compared to 77% in group 2 (relapsers) (p < 0.0001). In the maintenance
      treatment, the global response was 88% (39/44). The mean number of doses per
      patient was 4.4 +/- 2 (range 1-9) with a duration of 36 +/- 12 weeks (range 8
      72). Adverse effects were not significantly increased in either treatment.
      CONCLUSIONS: Both retreatment and long-term maintenance therapy with infliximab,
      are highly effective and well tolerated in fistulizing Crohn's disease patients.

PMID- 15449987
TI  - Abnormalities in liver enzyme levels during Salmonella enteritidis enterocolitis.
AB  - OBJECTIVE: To evaluate the prevalence, associated factors, and time-course
      changes of abnormal liver enzyme serum levels in adult patients with Salmonella
      enteritidis enterocolitis. METHODS: The clinical records of 104 patients (age
      range 15-86 years, 46.2% males) admitted to hospital because of S. enteritidis
      enterocolitis were reviewed. The prevalence of abnormal liver enzyme levels was
      evaluated, as well as its possible relationship to data of systemic inflammatory
      response, severe sepsis, and bacteremia. In addition, time-course changes in
      serum levels of liver enzymes were studied in 16 cases with available follow-up
      after hospital discharge. RESULTS: In patients without a pre-existing cause for
      liver enzyme abnormalities (n = 84), the prevalence of serum AST elevation was
      23.0% (95% CI 15.4-34.5%), of serum ALT elevation was 17.9% (95% CI 0.6-20.0%),
      and of GGT elevation was 19.0% (95% CI 11.6-29.3%). The prevalence of abnormality
      for any of these enzymes (AST, ALT, or GGT) was 35.7% (95% CI 25.7-46.8%). The
      prevalence of altered serum alkaline phosphatase was lower. Alteration in liver
      enzyme serum levels was moderate in the majority of cases, and was found in
      association with the presence of fever. Serum enzyme levels decreased during the
      convalescence period after hospital discharge. CONCLUSIONS: Abnormalities in
      liver enzyme levels are frequent during severe enterocolitis due to S.
      enteritidis in adult patients. These abnormalities are moderate and self-limited.

PMID- 15449988
TI  - Approaching focal liver lesions.

PMID- 15449989
TI  - Gastric stromal tumors: clinical presentation and surgical options.

PMID- 15449990
TI  - Adenomatous polyp in the gallbladder.

PMID- 15449991
TI  - [Chronic hepatitis B].

PMID- 15449992
TI  - [Synchronous colon adenocarcinoma during pregnancy].

PMID- 15449993
TI  - [Biliary cystadenoma with mesenchymal stroma "ovarian-like" and high levels of
      CA19.9].

PMID- 15450001
TI  - Systematics, evolution, and biology of scelionid and platygastrid wasps.
AB  - The Platygastroidea comprises two families of parasitoids, Scelionidae and
      Platygastridae, and nearly 4500 described species. They parasitize a diverse
      array of insects as well as spiders. Idiobiont endoparasitism of eggs is the
      putative ground plan biology, as reflected by all scelionids, but most
      Platygastridae are koinobiont endoparasitoids of immature Auchenorrhyncha,
      Sternorrhyncha, and Cecidomyiidae. The superfamily is demonstrably monophyletic
      but its phylogenetic position remains uncertain. Relationships within the
      Platygastroidea are also poorly known and the group is in need of comprehensive
      phylogenetic study. Significant information is available on host relationships
      and biology, although much of this is biased to a few genera of Telenominae that
      are employed as biocontrol agents. Hosts for many genera are unknown, in
      particular those that inhabit leaf litter or parasitize solitary host eggs. The
      Trissolcus basalis-Nezara viridula parasitoid-host association has become a
      favored model system in ecological, behavioral, and physiological research on
      insects.

PMID- 15450002
TI  - Cardiovascular risk factors and endothelial dysfunction.
AB  - Endothelial dysfunction is a feature of atherosclerosis and is associated with
      CHD (coronary heart disease) risk factors. This study aimed to determine the
      relationship between the degree of endothelial dysfunction and calculated
      cardiovascular risk. Endothelial function, as determined by the ACh/NP
      (acetycholine/sodium nitroprusside response) ratio on brachial plethysmography,
      was compared with cardiovascular risk as calculated from the Framingham, PROCAM
      (Prospective Cardiovascular Munster) and MRFIT (Multiple Risk Factor Intervention
      Trial) algorithms in 246 (187 male) patients, including 44 (22%) with established
      CHD. Endothelial dysfunction correlated with the total number of risk factors
      (r2=0.22; P=0.002) and was related to LDL (low-density lipoprotein)-cholesterol
      in men and triacylglycerols (triglycerides) in women. The ACh/NP ratio correlated
      with the occurrence of diabetes, CHD and the LDL-cholesterol concentration
      (r2=0.58; P<0.001). Endothelial dysfunction was associated with presence of CHD
      on receiver-operating characteristic plot analysis (area=0.706+/-0.04; P=0.001).
      There was no correlation between ACh/NP ratio and CHD risk calculated with the
      Framingham algorithm in men, although both ACh and NP response correlated
      separately with risk in women. The endothelial ACh/NP ratio correlated with
      absolute risk in the PROCAM algorithm (r2=0.41; P<0.005). Intermediate results
      were obtained with MRFIT. Individual risk factors make different contributions to
      endothelial dysfunction compared with their role in risk calculators. The
      stronger relationship of endothelial dysfunction with PROCAM risk reflects the
      contribution of male sex, LDL-cholesterol and triacylglycerols to risk calculated
      by this algorithm.

PMID- 15450004
TI  - Short and sweet: the perinatal origins of type 2 diabetes mellitus.

PMID- 15450005
TI  - Assessment of glycemic control by continuous glucose monitoring system in 50
      children with type 1 diabetes starting on insulin pump therapy.
AB  - OBJECTIVE: To report experience with a continuous glucose monitoring system
      (CGMS) and to identify factors influencing glycemic control in a large cohort of
      children and adolescents with type 1 diabetes and change to insulin pump therapy
      via continuous subcutaneous insulin infusion (CSII). RESEARCH DESIGN AND METHODS:
      In 50 patients [21 boys, 29 girls; median age 12.6 yr (range: 1.3-16.4 yr);
      diabetes duration 5.0 yr (0.2-13.3)], hemoglobin A1c (HbA1c) and ambulatory CGMS
      were performed before and 6 wk after starting CSII. Average glucose concentration
      per 24 h, during day and night time as well as number of excursions, duration,
      and area under the curve (AUC) of glucose values above 180 mg/dL and below 60
      mg/dL were calculated from CGMS data. Simultaneously, metabolic control was
      documented by standardized self-monitoring of blood glucose (SMBG). RESULTS: In
      the total cohort, HbA1c improved from 8.1 +/- 1.2% at baseline to 7.7 +/- 0.9%
      after 6 wk of CSII (p <0.001). This effect was more distinct in boys (8.0 +/- 1.4
      vs. 7.5 +/- 1.1%, p=0.007) than in girls (8.1 +/- 1.1 vs. 7.8 +/- 0.7%, p=0.039)
      as well as in patients with poor glycemic control (HbA1c >8.0%) at baseline (8.9
      +/- 0.6 vs. 8.1 +/- 0.8%, p <0.001) and in those older than 12 yr (8.2 +/- 1.2
      vs. 7.7 +/- 1.0%, p <0.001). At 6 wk of CSII, the values of glucose average per
      24 h, AUC and time above 180 mg/dL, particularly during the day, improved. HbA1c
      was correlated with AUC above 180 mg/dL (r=0.742, p <0.001) and CGMS average
      glucose per 24 h (r=0.628, p=0.002), but to a lesser extent with SMBG values
      (r=0.418, p=0.054). CONCLUSION: With the change to CSII, HbA1c improved
      significantly after 6 wk of therapy. CGMS usage provided additional information
      about glycemic control in these patients.

PMID- 15450006
TI  - Pubertal changes in HOMA and QUICKI: relationship to hepatic and peripheral
      insulin sensitivity.
AB  - BACKGROUND: Homeostasis model assessment (HOMA) and quantitative insulin
      sensitivity check index (QUICKI) are measures of insulin resistance and insulin
      sensitivity derived from fasting glucose (FG) and insulin levels. They thus
      should reflect, in principle, insulin action on both the liver and the periphery.
      METHODS: Twenty-three prepubertal and early pubertal adolescents were studied at
      baseline and after 6 months, using the frequently sampled intravenous glucose
      tolerance test (IVGTT) with labeled glucose. Total body insulin sensitivity (SI)
      was calculated using the minimal model and total glucose concentrations.
      Peripheral insulin sensitivity (SI*) was calculated from labeled glucose
      concentrations. Hepatic insulin resistance (HIR) was calculated by multiplying
      glucose production over the last hour by the average insulin level. HOMA and
      QUICKI were calculated from the fasting glucose and insulin values. RESULTS:
      HOMA, QUICKI fasting insulin, and glucose to insulin ratio were all significantly
      related to SI (p <0.05) but were not independently related to SI* or HIR.
      Multiple linear regression analysis revealed that both SI* and HIR independently
      predicted HOMA and fasting glucose (p <0.1). QUICKI, fasting insulin, and glucose
      to insulin ratio were not independently related to SI, SI*, or HIR. CONCLUSIONS:
      HOMA and fasting insulin reflect total body insulin sensitivity and HIR but not
      peripheral insulin sensitivity in prepubertal and early pubertal adolescents.

PMID- 15450003
TI  - The protein structures that shape caspase activity, specificity, activation and
      inhibition.
AB  - The death morphology commonly known as apoptosis results from a post
      translational pathway driven largely by specific limited proteolysis. In the last
      decade the structural basis for apoptosis regulation has moved from nothing to
      'quite good', and we now know the fundamental structures of examples from the
      initiator phase, the pre-mitochondrial regulator phase, the executioner phase,
      inhibitors and their antagonists, and even the structures of some substrates. The
      field is as well advanced as the best known of proteolytic pathways, the
      coagulation cascade. Fundamentally new mechanisms in protease regulation have
      been disclosed. Structural evidence suggests that caspases have an unusual
      catalytic mechanism, and that they are activated by apparently unrelated events,
      depending on which position in the apoptotic pathway they occupy. Some naturally
      occurring caspase inhibitors have adopted classic inhibition strategies, but
      other have revealed completely novel mechanisms. All of the structural and
      mechanistic information can, and is, being applied to drive therapeutic
      strategies to combat overactivation of apoptosis in degenerative disease, and
      underactivation in neoplasia. We present a comprehensive review of the caspases,
      their regulators and inhibitors from a structural and mechanistic point of view,
      and with an aim to consolidate the many threads that define the rapid growth of
      this field.

PMID- 15450007
TI  - Abnormal glucose tolerance in Egyptian beta-thalassemic patients: possible
      association with genotyping.
AB  - BACKGROUND: Type 1 diabetes mellitus (DM) is a frequent complication in patients
      with beta-thalassemia. It is believed to be due to the damage inflicted by iron
      overload of the pancreatic beta cells. Liver disorders and genetic influences
      seem to be additional predisposing factors. OBJECTIVE: To study the prevalence of
      diabetes and impaired glucose tolerance (IGT) in transfusion-dependent Egyptian
      beta-thalassemic patients and to evaluate the possible role of genotyping in the
      pathogenesis of diabetes associated with beta-thalassemia. RESEARCH DESIGN AND
      METHODS: A total of 56 transfusion-dependent beta-thalassemic patients aged 10-31
      (mean age=15.9 +/- 5.7 yr), 32 males and 24 females, including 48 thalassemia
      major and eight thalassemia intermedia; compared to 15 age- and sex-matched
      controls. All were subjected to history and examination, laboratory
      investigations: complete blood count (CBC), serum ferritin, liver function tests,
      hepatitis B and C markers, fasting blood glucose, oral glucose tolerance test
      (OGTT) and fasting C-peptide. Genotyping for 16 mutations was assessed in
      thalassemic patients with abnormal glucose tolerance. RESULTS: The prevalence of
      diabetes was 10.4% (5 of 48) and IGT was 14.6% (7 of 48) among thalassemia major,
      whereas, none of thalassemia intermedia had abnormal glucose tolerance. Fasting C
      peptide was lower in beta-thalassemic patients compared to controls (p <0.001);
      the level was significantly higher in patients complicated by diabetes or IGT
      compared with other thalassemic patients (p <0.001). Chronic hepatitis C was
      detected in all patients (100%) with abnormal glucose tolerance. Genotyping
      showed that IVS II nt 745 was detected in 77.7% of cases with abnormal glucose
      tolerance. CONCLUSIONS: Abnormal glucose tolerance is common in multiply
      transfused beta-thalassemia major patients, which could be attributed to
      progressive and early loss of beta-cell mass, along with persistent insulin
      resistance. Chronic hepatitis C may play a role in the development of abnormal
      glucose tolerance. An association between diabetes and genotyping IVS II nt 745
      was found. Patients with this particular genotype are advised to check their
      blood glucose every 6 months to detect early occurrence of diabetes.

PMID- 15450008
TI  - Reimbursement and costs of pediatric ambulatory diabetes care by using the
      resource-based relative value scale: is multidisciplinary care financially
      viable?
AB  - BACKGROUND: The ambulatory care for children with diabetes mellitus (DM) within
      an endocrinology specialty practice typically includes services provided by a
      multidisciplinary team. The resource-based relative value scale (RBRVS) is
      increasingly used to determine payments for ambulatory services in pediatrics. It
      is not known to what extent resource-based practice expenses and physician work
      values as allocated through the RBRVS for physician and non-physician practice
      expenses cover the actual costs of multidisciplinary ambulatory care for children
      with DM. STUDY SETTING: A pediatric endocrinology and diabetes clinic staffed by
      faculty physicians and hospital support staff in a children's hospital. METHODS:
      Data from a faculty practice plan billing records and income and expense reports
      during the period from 1 July 2000 to 30 June 2001 were used to determine
      endocrinologist physician ambulatory productivity, revenue collection, and direct
      expenses (salary, benefits, billing, and professional liability (PLI)). Using the
      RBRVS, ambulatory care revenue was allocated between physician, PLI, and practice
      expenses. Applying the activity-based costing (ABC) method, activity logs were
      used to determine non-physician and facility practice expenses associated with
      endocrine (ENDO) or diabetes visits. RESULTS: Of the 4735 ambulatory
      endocrinology visits, 1420 (30%) were for DM care. Physicians generated $866,582
      in gross charges. Cash collections of 52% of gross charges provided revenue of
      $96 per visit. Using the actual Current Procedural Terminology (CPT)-4 codes
      reported for these services and the RBRVS system, the revenue associated with the
      13,007 total relative value units (TRVUs) produced was allocated, with 58% going
      to cover physician work expenses and 42% to cover non-physician practice salary,
      facility, and PLI costs. Allocated revenue of $40.60 per visit covered 16 and 31%
      of non-physician and facility practice expenses per DM and general ENDO visit,
      respectively. RBRVS payments ($35/RVU) covered 46% of all expenses ($76.74/RVU),
      including 132% of physician expenses for the time worked in the clinic ($27/RVU),
      and only 23% of actual incurred practice expenses ($152/TRVU). CONCLUSIONS:
      Clinical revenues in a pediatric endocrinology practice, allocated by using the
      RBRVS system, do cover physician expenses for the time spent working in a
      hospital ENDO and DM clinic, but do not closely approximate non-physician and
      facility practice expenses while delivering multidisciplinary care to children
      with DM. Using payment based on the RBRVS system, and without additional payments
      to compensate for increased practice expenses incurred in the delivery of
      multidisciplinary care, this care model may not be financially viable.

PMID- 15450009
TI  - Glucose tolerance of 2- to 5-yr-old offspring of diabetic mothers.
AB  - The aim of this study was to determine the prevalence of and some risk factors
      for impaired glucose tolerance (IGT) in 2- to 5-yr-old offspring of diabetic
      mothers (ODM). The glucose tolerance of 51 offspring born to women with
      pregnancies complicated by diabetes (type 1) and of 109 children of the control
      group was analyzed. Our results showed that the fasting glycemia of ODM was
      similar, when compared to the controls, but 2 h after the glucose loading the
      glycemia of ODM was significantly higher than that in the control group (5.47 +/-
      1.79 mmol/L vs. 4.86 +/- 1.13 mmol/L). Normal glucose tolerance was found in
      68.6% of ODM and 86.2% of controls; IGT was found in 17.6% of ODM and 4.6% of
      controls. Children with macrosomia at birth or overweight at 2-5 yr had IGT at 2
      5 yr more often than children with normal weight at birth or normal weight at 2-5
      yr. A significant, though relatively low, positive correlation was found between
      the duration of breastfeeding and fasting glycemia (r=0.241, p <0.01), and
      positive correlation was found between the duration of breastfeeding and glycemia
      2 h after glucose loading (r=0.458, p=0.002) in the offspring of diabetic
      mothers. In conclusion, the average glycemia of ODM after glucose loading was
      higher than that in the control group. Macrosomia after birth, overweight, and
      obesity in childhood had a significant influence on the glucose tolerance of the
      ODM. The results of the oral glucose tolerance test correlated with the length of
      breastfeeding.

PMID- 15450010
TI  - Long-term metabolic consequences of being born small for gestational age.
AB  - This review highlights the evidence of linking small for gestational age (SGA)
      with metabolic/cardiovascular disturbances (dysmetabolic syndrome) in later life.
      The metabolic and cardiovascular complications associated with in utero
      undernutrition have been identified during the past 10 yr. Reduced fetal growth
      is independently associated with an increased risk of the development of
      cardiovascular diseases, the insulin-resistance syndrome, or one of its
      components: hypertension, dyslipidemia, impaired glucose tolerance, or type 2
      diabetes. All of them appear to result from the initial development of insulin
      resistance which appears as a key component underlying the metabolic
      complications. Although the mechanism remains unclear, there is some evidence
      that argues in favor of an active contribution of the adipose tissue in the
      emergence of insulin-resistance associated with in utero undernutrition, but this
      hypothesis remains to be further documented. From a broader point of view,
      several hypotheses have been proposed over the past 10 yr to understand this
      unexpected association. Each of them points to either a detrimental fetal
      environment or genetic susceptibilities or interactions between these two
      components as playing a critical role in this context. Although not confirmed,
      the hypothesis suggesting that this association could be the consequence of
      genetic/environmental interactions remains at the moment the most attractive.

PMID- 15450011
TI  - Epidemiology of childhood type 2 diabetes in the developing world.
AB  - Type 2 diabetes in the young is an increasing problem with potentially serious
      outcomes. Our understanding of the worldwide burden of this condition is
      incomplete, with many studies adopting different methodologies to assess the
      condition and reporting on specific communities or ethnic groups. Most of the
      data come from developed nations, with few studies from developing nations. The
      purpose of this review is to bring together the available data on type 2 diabetes
      in the young from the developing world, in order to highlight deficiencies in the
      knowledge of the condition and also to promote strategies to deal with it. Noted
      also are some of the factors associated with the condition, such as family
      history, genetic influences, intrauterine environment as well as the importance
      of birth weight, insulin resistance, obesity, and development of complications.
      These are of relevance in both developed and developing nations.

PMID- 15450013
TI  - Abstracts of the XXV Congress of the International Academy of Pathology. October
      10-15, 2004. Queensland, Australia.

PMID- 15450014
TI  - Abstracts of the XXV Congress of the International Academy of Pathology. 2004.

PMID- 15450015
TI  - Impact of emotional abuse on the individual.

PMID- 15450016
TI  - Computerized cognitive-behaviour therapy for anxiety and depression: a practical
      solution to the shortage of trained therapists.
AB  - Computerized cognitive-behaviour therapy (CCBT) programmes have been developed to
      help meet the enormous need for evidence-based psychological treatment of common
      mental health problems in the context of a severe shortage of trained therapists
      to meet that need. Randomized controlled trials have confirmed the efficacy of
      such programmes. We present the experience of a community mental health team
      (CMHT) resource centre with one such programme, Beating the Blues, together with
      outcome data on a small sample of its clients. We conclude that experience and
      data, taken together, demonstrate the practical benefits of CCBT in routine
      practice.

PMID- 15450017
TI  - Primary health care practitioners' tools for mental health care.
AB  - The purpose of this study was to describe and analyse the content of mental
      health care from the practitioner's point of view. The specific aim of this paper
      was to outline the types of mental health care tools and the ways in which they
      are used by primary health care practitioners. The data were derived from
      interviews with doctors and nurses (n = 29) working in primary health care in six
      different health care centres of the Pirkanmaa region in Finland. The data were
      analysed by using qualitative content analysis. The tools of mental health care
      used in primary health care were categorized as communicative, ideological,
      technical and collaborative tools. The interactive tools are either informative,
      supportive or contextual. The ideological tools consist of patient initiative,
      acceptance and permissiveness, honesty and genuineness, sense of security and
      client orientation. The technical tools are actions related to the monitoring of
      the patient's physical health and medical treatment. The collaborative tools are
      consultation and family orientation. The primary health care practitioner
      him/herself is an important tool in mental health care. On the one hand, the
      practitioner can be categorized as a meta-tool who has control over the other
      tools. On the other hand, the practitioner him/herself is a tool in the sense
      that s/he uses his/her personality in the professional context. The professional
      skills and attitudes of the practitioner have a significant influence on the type
      of caring the client receives. Compared with previous studies, the present
      informants from primary health care seemed to use notably versatile tools in
      mental health work. This observation is important for the implementation and
      development of mental health practices and education.

PMID- 15450018
TI  - A comparison of the work and values of community mental health nurses in two
      mental health NHS Trusts.
AB  - With the reconfiguration of health services in both the primary and secondary
      sectors, the role of community mental health nurses (CMHNs) has become a highly
      contested one within mental health care. There would be great variability in the
      skills that CMHNs possess, the contexts in which they work and the nature of the
      work they do. This study sought to explore aspects of the work of those nurses
      who provide services at the interface between policy and practice. Two groups of
      CMHNs were compared, one working in an urban setting (Trust A) and the other in a
      rural (Trust B), focusing particularly on caseloads and client mix, the values
      held by CMHNs, the models of care they utilize and what they consider would
      improve care in the future. A specially designed 39-item questionnaire was
      employed, with a mix of open and closed questions, and statements to which
      participants were asked to respond on a three-point Likert scale. The findings
      raised interesting issues around collaborative working, whether CMHNs are happy
      to take on clients previously on their caseload, bureaucratization, autonomy,
      role definition within a culture of working with primary care, lack of specific
      models utilized by CMHNs, and the demand for greater training and educational
      support. The implications of the study are discussed with the aim of assisting
      mental health nurses determine their future roles.

PMID- 15450019
TI  - Promoting psychiatric student nurse well-being.
AB  - Although students are often attracted to the profession of psychiatric nursing,
      they are rarely prepared for the realities associated with clinical seminars and
      direct clinical practice. Subsequently, student nurses commonly report the
      resurgence of painful life events or symptoms of psychological injury when
      learning about or witnessing patient behaviour. This paper underlines the
      importance of student-faculty collaboration when promoting and monitoring student
      nurse well-being. Along with providing descriptions and case vignettes depicting
      two specific forms of psychological injury, this paper suggests practical steps
      that are designed to promote student nurse well-being.

PMID- 15450020
TI  - The use of touch to enhance nursing care of older person in long-term mental
      health care facilities.
AB  - The self-care deficits experienced by older clients in long-term mental health
      settings, because of cognitive impairment, are likely to impact upon the clients'
      higher-order needs. The practice of nursing the elderly involves a lot of
      personal contact, during the delivery of fundamental physical care. While
      physiological and safety needs are crucial to clients in long-term settings,
      higher-order needs need also to be addressed. From the clients' perspective
      nurse's use of touch provides comfort, warmth and security, although there is a
      dearth of empirical evidence of these benefits. This paper explores the nurse's
      use of touch, the impact of touch and the experiences of touch on the older
      person in long-term settings. Because of the dearth of research in the use of
      touch with elderly clients in long-term care mental health facilities, a review
      of the literature was performed on the topic. This revealed that touch by nurses
      is frequently associated with routine tasks within nursing, and is less likely to
      be a caring touch intervention. Recommendations include further research on the
      topic and caution with widespread adoption of caring touch as an intervention.

PMID- 15450021
TI  - Judging the other: psychiatric nurses' attitudes towards identified inpatients as
      measured by the semantic differential technique.
AB  - Nurses' attitudes towards psychiatric patients can be expressed in terms of
      either a symptom-oriented approach or a personhood-focused approach where the
      latter is characterized by the ambition to establish a genuine and lasting
      relationship, while the former places the emphasis on correcting 'defective'
      patient behaviour. To study whether previous typologies found in a qualitative in
      depth interview study exist in a larger quantitative investigation and, if so, to
      identify and describe a structure for the nurses' attitudes connected to each of
      the identified typologies. Six psychiatric group dwellings and six acute
      psychiatric hospital wards participated in the study. In all, 2700 assessments of
      163 patients were sent out to 160 respondents and 2436 answers were returned,
      that is, the external dropout rate was 9.8%. The semantic differential technique
      was used. This is a method for quantifying the meaning that is attached to an
      identified phenomenon through series of bipolar pairs of adjectives. The scale
      has 57 bipolar pairs of adjectives, which estimates an unknown number of
      dimensions of nurses' attitudes towards an identified patient. The respondents'
      answers were analysed through entropy-based measures of association combined with
      structural plots. The analysis revealed that the four typologies existed as a
      delimited group, especially the groups of 'good' and 'evil' patients, while the
      'crazy' and 'invisible' patients existed in a more blurred form. The analysis
      also revealed that the two groups, 'good' and 'evil', were connected to the
      nurses' ethical and aesthetic attitude structure, while the 'crazy' patients were
      linked to the cognitive structure and the 'invisible' patients to the empathetic
      structure. The study indicates that the two typologies, 'good' and 'evil', could
      be seen as each other's antithesis and, together with the other two typologies,
      'crazy' and 'invisible', they touched upon a structure of the nurses' attitudes
      that was closely connected to a negative view of the patient except in one case 
      'the good' patients, which was probably based on his/her exterior symptoms.

PMID- 15450022
TI  - 'Finding the person the disease has'--the case for multisensory environments.
AB  - Education about, and exposure to, the utilization of a multisensory environment
      (MSE) was provided to clinical staff as a response to findings from the problem
      identification stage of an action research study. Feedback was obtained about
      their experience and perceptions of its use. Through the auspices of focus groups
      and one-to-one interviews, respondents commented on the impact that using the MSE
      had on their perception of their clients and on subsequent care. The case is made
      that MSEs afford an opportunity to impact on care through their mediating
      influence on formal carers' perceptions of their clients and, as such represent a
      significant but as yet unrealized potential for improving the quality of care of
      older people with dementia.

PMID- 15450023
TI  - Return to the asylum: the search for clients with enduring mental health problems
      in Italy.
AB  - Deinstitutionalization and community care were the most influential movements in
      the field of mental health in the last 30 years. In 1978 Italy was the first
      country to pass laws that would eliminate mental hospitals and replace them with
      community-based services. Italian ideas about community care provided inspiration
      for care in the community legislation when this was introduced in the UK. In
      order to be able to fairly assess and describe the benefits of Italian mental
      health care, the author visited a range of care facilities in a prescribed region
      in the north of Italy. In the course of investigation, the author sought to
      discover if the implementation of what were regarded by some as radical community
      attitudes in the care of people with mental health problems had led to innovative
      approaches when dealing with patients/clients requiring long-term care and
      treatment. Although the Italian approach is enlightened in many areas of care,
      the system still has to face up to the problems presented in caring for
      clients/patients with enduring mental health problems. The circumstances relating
      to care were unexpected and caused the author to revise his opinion of the
      Italian approach to community care.

PMID- 15450024
TI  - Relapse signatures and insight: implications for CPNs.
AB  - Schizophrenia is, largely, an episodic illness with periods of remission and
      relapse. Early warning signs (EWS) strategies provide a guide to patients, their
      carer and mental health worker, to collaboratively manage relapse by identifying
      each individual's EWS of relapse, and agree a plan of action should EWS occur.
      Although there is evidence to suggest these strategies can reduce
      hospitalization, the psycho-educational component is likely to impact on the
      patient's insight. Rapid increases in insight have been associated with low mood.
      Consequently the clinician using this strategy risks unintended negative
      consequences. This paper argues that the flexible and broad community psychiatric
      nurse role means they are in an ideal position to address this possible pitfall,
      whilst maximizing the benefits of the strategy.

PMID- 15450025
TI  - Conversation starters: re-examining and reconstructing first encounters within
      the therapeutic relationship.
AB  - This paper describes, analyses and reconstructs early encounters between nurse
      and client. Too often nurses take for granted ordinary encounters with clients
      and thus overlook opportunities to develop the nurse-client relationship. Common
      encounters, drawn from reflection on practice, are analysed using contemporary
      cultural theories. Creative alternatives are suggested and we argue that they
      represent opportunities to make meaningful connections with and for clients. As
      conversation starters, these ideas may be used by nurses to facilitate a more
      trusting therapeutic relationship. They may help to deepen understanding or
      insight into mental health problems and help to reveal hidden strengths and
      solutions. By noticing, valuing, discussing and developing this space, we as
      mental health nurses are extending our discipline base and articulating, with
      more precision and persuasion, exactly how we contribute to better health
      outcomes.

PMID- 15450026
TI  - Psychiatric ethics; a critical introduction for mental health nurses.
AB  - Drawing upon the author's experience as a mental health nurse lecturer, this
      paper suggests that many mental health nurses seem to have difficulty engaging
      with the ethical issues in psychiatry, and appreciating the relevance of those
      issues to their everyday practice. In an attempt to address this difficulty, this
      paper will present a framework that can serve as an accessible introduction to
      the ethical issues in psychiatry. Reflecting upon general, clinical examples from
      psychiatric practice, it will be suggested that many ethical issues in psychiatry
      are concerned with acts of paternalism and with the common justification for
      those acts. Having presented this framework, the paper will then subject it to a
      preliminary critique by drawing upon contemporary, critical approaches to health
      care ethics. It is hoped that this will serve to stimulate both a deeper
      appreciation of the relevance of ethics to the practice of mental health nursing
      and an ongoing critical consideration of the ethical issues in psychiatry.

PMID- 15450027
TI  - Challenging gender stereotypes in the counselling of adult survivors of childhood
      sexual abuse.
AB  - When working with adult survivors of childhood sexual abuse, the pairing of
      client with practitioner has implications for both parties. Many therapeutic
      pairings are ad hoc or based on stereotypical assumptions made by referrers or
      practitioners themselves. This paper reports on a small-scale study of
      practitioners working in the mental health directorate of an NHS Trust in Wales.
      One aim of the study was to explore practitioners' views on appropriate
      therapeutic pairings. Fifty-three respondents completed a postal questionnaire
      and six face-to-face interviews were also conducted. Key themes emerged from the
      study. These were social and cultural stereotyping, gender specific issues, the
      therapeutic relationship, service and professional issues and special opinions
      and unique angles. The terms 'therapist' and 'practitioner' will be used
      interchangeably in this paper.

PMID- 15450028
TI  - The effectiveness of two interventions in the management of patient violence in
      acute mental inpatient settings: report on a pilot study.
AB  - Systematic risk assessment and training courses have been suggested as
      interventions to deal with patient violence in psychiatric institutions. A dual
      centre prospective feasibility study was conducted on two Swiss psychiatric
      admission wards to test the hypothesis that such interventions will reduce the
      frequency and severity of violent events and coercion. A systematic aggression
      risk assessment, in combination with a standardized training course in aggression
      management was administered and the frequency and severity of aggressive
      incidents and the frequency of coercive measures were registered. The incidence
      rates of aggressive incidents and attacks showed no significant reduction from
      the baseline through risk prediction and staff training, but the drop in coercive
      measures was highly significant. A 'ward effect' was detected with one ward
      showing a decline in attacks with unchanged incidence rates of coercion and the
      other ward showing the opposite. The severity of the incidents remained unchanged
      whilst the subjective severity declined after the training course. We conclude
      that a systematic risk assessment and a training course may assist in reducing
      the incidence rate of coercive measures on psychiatric acute admission wards.
      Further testing of the interventions is necessary to measure the effect of the
      training alone and to counteract 'ward effects'.

PMID- 15450029
TI  - Education and training in psychosocial interventions: a survey of Thorn
      Initiative course leaders.
AB  - The Thorn Initiative is a prominent education and training programme for
      psychosocial interventions. The course originated in two centres in the UK in
      1992, 10 years on the programme had expanded to 13 centres across England and
      Wales. A survey of course content and structure was sent out to all 13 sites by
      email of which eight responded by post. The survey results showed that since 1999
      there has been a rapid growth in the number of Thorn sites. There remains a high
      degree of fidelity to the original courses in mode of delivery, service user and
      carer participation, and core content. All of the sites were progressing towards
      providing degree courses, usually in a modular format and with an expanded
      curriculum. In conclusion, the Thorn Steering Group has been successful in Thorn
      site expansion and curriculum development. Such success has taken activity away
      from audit and research in psychosocial interventions, education, training,
      implementation and fidelity to taught skills. Implementation remains a cause for
      concern and it is recommended that a focus for Thorn sites should be on creating
      and evaluating novel solutions to this pervasive problem.

PMID- 15450030
TI  - Family burden and participation in care: differences between relatives of
      patients admitted to psychiatric care for the first time and relatives of re
      admitted patients.
AB  - Studies on emotional and physical strain imposed on family members in connection
      with their responsibility of caring for a person with a severe mental illness
      have focused on the chronic patients. The situation of family members with
      patients who are at an early stage of illness and admitted for the first time may
      illuminate different patterns. In this Swedish multi-centre study, 162 relatives
      of patients in acute psychiatric wards, both those admitted for the first time
      and those re-admitted, were interviewed concerning their experience of family
      burden and their participation in care. There were relatively few differences
      found in burden measures and participation in care between the two subgroups of
      relatives. However, relatives who were in a career of being a relative to a
      person with severe mental illness earlier, more often viewed the psychiatric
      services to be of good quality, although they had had less contact with the staff
      of the psychiatric services during the last year. The relatives of re-admitted
      patients experience more often psychological aspects of burden, equivalent to
      associated stigma. The future task of maintaining the relatives' good opinion of
      psychiatric services, as well as the issue of giving informationare discussed.

PMID- 15450031
TI  - Developing and testing instruments for improving cooperation and patient's
      participation in mental health care.
AB  - The main purpose of the project was to develop computerized instruments that
      could be used by nurses and patients to assess their cooperation and mutual
      contributions to care. This paper presents a part of the project: the reliability
      and validity testing phase of a process of instrument development. To test the
      validity and reliability of the instruments, data were collected with
      questionnaires from nurses (n = 146) and patients (n = 286). The validity
      evaluated as construct validity and the reliability evaluated as internal
      consistency of the instruments were quite good. Construct validity was tested by
      factor analysis, and internal consistency was tested by Cronbach's alpha
      coefficient, which varied from 0.69 to 0.79. The instruments, which consisted of
      a software application that can be operated in a www environment, were meant to
      be used as tools in the psychiatric nursing context for assessing the cooperation
      between the nurses and patients and the patient's participation in his/her care.
      Furthermore, the computer programme can be used as a tool for developing and
      assessing the patient orientation in nursing.

PMID- 15450032
TI  - Anything to declare? Competing interests in mental health nursing journals.

PMID- 15450033
TI  - Acute psychiatric ward rules: a review of the literature.
AB  - This literature review forms a background element of a comparative study of two
      acute psychiatric wards in the East End of London. The research focused on ward
      rules as a means of investigating the relationship between the
      flexibility/inflexibility of ward nursing regimes and patient outcomes. Previous
      studies identified a relationship between ward rules and patient aggression.
      Other studies identified a link between absconding by inpatients and nurses'
      attitudes towards rule enforcement. However, an in-depth exploration of
      psychiatric ward rules from the perspective of nurses and patients has not been
      undertaken previously.

PMID- 15450034
TI  - Outcome predictors of pneumonia in elderly patients: importance of functional
      assessment.
AB  - OBJECTIVES: To evaluate the outcome of elderly patients with community-acquired
      pneumonia (CAP) seen at an acute-care hospital, analyzing the importance of CAP
      severity, functional status, comorbidity, and frailty. DESIGN: Prospective
      observational study. SETTING: Emergency department and geriatric medical day
      hospital of a university teaching hospital. PARTICIPANTS: Ninety-nine patients
      aged 65 and older seen for CAP over a 6-month recruitment period. MEASUREMENTS:
      Clinical data were used to calculate Pneumonia Severity Index (PSI), Barthel
      Index (BI), Charlson Comorbidity Index, and Hospital Admission Risk Profile
      (HARP). Patients were then assessed 15 days later to determine functional decline
      and 30 days and 18 months later for mortality and readmission. Multiple logistic
      regression was used to analyze outcomes. RESULTS: Functional decline was observed
      in 23% of the 93 survivors. Within the 30-day period, case-fatality rate was 6%
      and readmission rate 11%; 18-month rates were 24% and 59%, respectively. Higher
      BI was a protective factor for 30-day and 18-month mortality (odds ratio
      (OR)=0.96, 95% confidence interval (CI)=0.94-0.98 and OR=0.97, 95% CI=0.95-0.99,
      respectively; P<.01), and PSI was the only predictor for functional decline
      (OR=1.03, 95% CI=1.01-1.05; P=.01). Indices did not predict readmission. Analyses
      were repeated for the 74 inpatients and indicated similar results except for 18
      month mortality, which HARP predicted (OR=1.73; 95% CI=1.16-2.57; P<.01).
      CONCLUSION: Functional status was an independent predictor for short- and long
      term mortality in hospitalized patients whereas CAP severity predicted functional
      decline. Severity indices for CAP should possibly thus be adjusted in the elderly
      population, taking functional status assessment into account.

PMID- 15450035
TI  - Behavioral symptoms in residential care/assisted living facilities: prevalence,
      risk factors, and medication management.
AB  - OBJECTIVES: To examine the prevalence, correlates, and medication management of
      behavioral symptoms in elderly people living in residential care/assisted living
      (RC/AL) facilities. DESIGN: Cross-sectional study. SETTINGS: A stratified random
      sample of 193 RC/AL facilities in four states (Florida, Maryland, New Jersey,
      North Carolina). PARTICIPANTS: A total of 2,078 RC/AL residents aged 65 and
      older. MEASUREMENT: Behavioral symptoms were classified using a modified version
      of the Cohen-Mansfield Agitation Inventory. Additional items on resistance to
      care were also examined. RESULTS: Approximately one-third (34%) of RC/AL
      residents exhibited one or more behavioral symptoms at least once a week.
      Thirteen percent exhibited aggressive behavioral symptoms, 20% demonstrated
      physically nonaggressive behavioral symptoms, 22% expressed verbal behavioral
      symptoms, and 13% resisted taking medications or activities of daily living care.
      Behavioral symptoms were associated with the presence of depression, psychosis,
      dementia, cognitive impairment, and functional dependency, and these
      relationships persisted across subtypes of behavioral symptoms. Overall,
      behavioral symptoms were more prevalent in smaller facilities. More than 50% of
      RC/AL residents were taking a psychotropic medication, and two-thirds had some
      mental health problem indicator (dementia, depression, psychosis, or other
      psychiatric illness). CONCLUSION: Integrating mental health services within the
      process of care in RC/AL is needed to manage and accommodate the high prevalence
      of behavioral symptoms in this evolving long-term setting.

PMID- 15450036
TI  - The Maryland Assisted Living Study: prevalence, recognition, and treatment of
      dementia and other psychiatric disorders in the assisted living population of
      central Maryland.
AB  - OBJECTIVES: To obtain a direct estimate of the prevalence of dementia and other
      psychiatric disorders in residents of assisted living (AL) in Central Maryland,
      and their rates of recognition and treatment. DESIGN: Comprehensive review of
      history and cognitive and neuropsychiatric evaluations using widely accepted
      instruments in a randomized cohort of AL residents, stratified by facility size.
      An expert multidisciplinary consensus panel determined diagnoses and
      appropriateness of treatment. SETTING: Twenty-two (10 large and 12 small)
      randomly selected AL facilities in the city of Baltimore and seven Maryland
      counties. PARTICIPANTS: One hundred ninety-eight volunteers who were residents of
      AL, 75% were aged 80 and older, and 78% were female. Potential participants were
      randomly chosen by room number. There was a 67% participation rate. MEASUREMENTS:
      Overall rate of dementia, noncognitive active psychiatric disorders, and
      recognition and adequate treatment of dementia and psychiatric disorders, as
      determined by consensus panel. RESULTS: Two-thirds (67.7%) of participants had
      dementia diagnosable according to the Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition (81% small facilities and 63% large). Family or
      caregivers recognized 78% to 80% of dementias. Seventy-three percent of dementias
      were adequately evaluated, and 52% were adequately treated. Of the 26.3% of
      participants who had an active noncognitive psychiatric disorder, 58% to 61% were
      recognized and 52% adequately treated. CONCLUSION: Dementia and psychiatric
      disorders are common in AL and have suboptimal rates of recognition and
      treatment. This may contribute to morbidity and interfere with the ability of
      residents to age in place.

PMID- 15450037
TI  - Chlamydia pneumoniae seropositivity and cardiovascular risk factors: The
      InCHIANTI Study.
AB  - OBJECTIVES: To assess the prevalence of Chlamydia pneumoniae (CP) seropositivity
      and test the hypothesis that CP infection (CPI) is associated with cardiovascular
      (CV) risk factors and levels of inflammatory biomarkers. DESIGN: Cross-sectional
      survey. SETTING: Representative sample of the residents of Greve in Chianti and
      Bagno a Ripoli, two small towns located in the Chianti geographic area (Tuscany,
      Italy). PARTICIPANTS: A total of 1,304 (age-range: 20-103, 79% aged> or =65)
      participants of the InCHIANTI study. MEASUREMENTS: CP seropositivity was assessed
      using immunofluorescence. Previous CPI was defined as immunoglobulin (Ig) G > or
      =1/16 and <1/256, and recent CPI was defined as IgG > or =1/512 or IgM > or
      =1/16. Inflammatory markers included interleukin (IL)-6, soluble IL-6 receptor
      (sIL-6r), tumor necrosis factor-alpha (TNF-alpha), IL-1beta, IL-1 receptor
      antagonist (IL-1ra), iron, ferritin, and C-reactive protein (CRP). CV risk
      factors included smoking, body mass index (BMI), lipid profile, and hypertension.
      RESULTS: The prevalence of CP seropositivity was 75%, increased with age, and was
      higher in men than in women (P<.01). CPI was not associated with IL-1beta, IL
      1ra, iron, ferritin, CRP, BMI, lipids, and smoking. After adjusting for age and
      sex, previous or recent CPI was associated with higher TNF-alpha (P<.01), IL-6
      (P<.03), sIL-6R (P<.01), and hypertension (P<.02). In additional age and sex
      adjusted models, the associations between CPI and TNF-alpha, IL-6, sIL-6r, and
      hypertension appeared to be mutually independent. CONCLUSION: CP seropositivity
      is highly prevalent in the older population and is a significant, independent
      correlate of hypertension and circulating levels of TNF-alpha, IL-6, and sIL-6r.

PMID- 15450038
TI  - Longitudinal study of determinants of dependence in an elderly population.
AB  - OBJECTIVES: To describe those factors, from the host of initial measures in
      ambulatory, independent older men and women, that were determinants of becoming
      dependent over an 8-year follow-up. DESIGN: Initial measures in a cohort of
      independent older adults were used in logistic regression to describe the
      determinants of becoming dependent at the 8-year follow-up. SETTING: London,
      Ontario. PARTICIPANTS: Three hundred seventy-three men and women aged 55 to 86.
      MEASUREMENTS: Initial variables included body size, presence of chronic disease,
      maximal oxygen uptake (VO2max), strength, flexibility, walking pace, and leisure
      time physical activity. RESULTS: An 8-year follow-up of 297 participants
      identified 43 as dependent. Logistic regression showed age, presence of disease,
      and VO2max (cardiorespiratory fitness) at baseline to have significant odds
      ratios related to the outcome of becoming dependent. Controlling for other
      factors, a lower VO2max increased the odds of dependence by 14% for each
      mL/kg.min. CONCLUSION: Lower cardiorespiratory fitness was a significant
      determinant of becoming dependent in an 8-year follow-up of older adults.
      Initiatives to encourage physical activity in older adults should emphasize
      exercise, such as brisk walking, to maintain or improve cardiorespiratory
      fitness.

PMID- 15450039
TI  - The association between lipid levels and the risks of incident myocardial
      infarction, stroke, and total mortality: The Cardiovascular Health Study.
AB  - OBJECTIVES: To assess the association between lipid levels and cardiovascular
      events in older adults. DESIGN: A prospective population-based study. SETTING:
      Four field centers in U.S. communities. PARTICIPANTS: A total of 5,201 adults
      aged 65 and older living in U.S. communities, plus a recruitment of 687 African
      Americans 3 years later. MEASUREMENTS: Fasting lipid measures included low
      density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol
      (HDL-C), total cholesterol, and triglycerides. RESULTS: At baseline, 1,954 men
      and 2,931 women were at risk for an incident myocardial infarction (MI) or
      stroke. During an average 7.5-year follow-up, 436 subjects had a coronary event,
      332 had an ischemic stroke, 104 a hemorrhagic stroke, and 1,096 died. After
      adjustment, lipid measures were not major predictors of the outcomes of MI,
      ischemic stroke, hemorrhagic stroke, and total mortality. For total cholesterol
      and LDL-C, the associations with MI and ischemic stroke were only marginally
      significant. HDL-C was inversely associated with MI risk (hazard ratio=0.85 per
      standard deviation of 15.7 mg/dL, 95% confidence interval=0.76-0.96). For the
      outcome of ischemic stroke, high levels of HDL-C were associated with a decreased
      risk in men but not women. Lipid measures were generally only weakly associated
      with the risks of hemorrhagic stroke or total mortality. CONCLUSION: In this
      population-based study of older adults, most lipid measures were weakly
      associated with cardiovascular events. The association between low HDL-C and
      increased MI risk was nonetheless strong and consistent.

PMID- 15450040
TI  - Risk of congestive heart failure in an elderly population treated with peripheral
      alpha-1 antagonists.
AB  - OBJECTIVES: To compare the risk of congestive heart failure (CHF) in elderly
      individuals treated with any peripheral alpha-1 antagonist for hypertension with
      any thiazide, test whether the risk persists in subjects without cardiovascular
      disease (CVD) at baseline, and examine CHF risk in normotensive men with
      prostatism treated with alpha antagonists. DESIGN: Prospective cohort study.
      SETTING: Four U.S. sites: Washington County, Maryland; Allegheny County,
      Pennsylvania; Sacramento County, California; and Forsyth County, North Carolina.
      PARTICIPANTS: A total of 5,888 community-dwelling subjects aged 65 and older.
      MEASUREMENTS: Adjudicated incident CHF. RESULTS: The 3,105 participants with
      treated hypertension were at risk for CHF; 22% of men and 8% of women took alpha
      antagonists during follow-up. The age-adjusted risk of CHF in those receiving
      monotherapy treated with alpha antagonists was 1.90 (95% confidence interval=1.03
      3.50) compared with thiazides. In subjects without CVD at baseline receiving
      monotherapy, women taking an alpha antagonist had a 3.6 times greater age
      adjusted risk of CHF, whereas men had no difference in risk. Adjustment for
      systolic blood pressure attenuated statistical differences in risk. There were
      930 men without hypertension at risk for CHF; 5% used alpha antagonists during
      follow-up, with no observed increase in CHF risk. CONCLUSION: Subjects receiving
      alpha antagonist monotherapy for hypertension had a two to three times greater
      risk of incident CHF, also seen in lower-risk subjects, but differences in blood
      pressure control partly explained this.

PMID- 15450041
TI  - A matched-cohort study of health services utilization and financial outcomes for
      a heart failure disease-management program in elderly patients.
AB  - OBJECTIVES: To investigate the utilization and financial outcomes of a telephonic
      nursing disease-management program for elderly patients with heart failure.
      DESIGN: A 1-year concurrent matched-cohort study employing propensity score
      matching. SETTING: Medicare+Choice recipients residing in Ohio, Kentucky, and
      Indiana. PARTICIPANTS: A total of 533 program participants aged 65 and older
      matched to nonparticipants. INTERVENTION: Disease-management heart failure
      program employing a structured, evidence-based, telephonic nursing intervention
      designed to provide patient education, counseling, and monitoring services.
      MEASUREMENTS: Medical service utilization, including hospitalizations, emergency
      department visits, medical doctor visits, skilled nursing facility (SNF) days,
      selected clinical indicators, and financial effect. RESULTS: The intervention
      group had considerably and significantly lower rates of acute service utilization
      than the control group, including 23% fewer hospitalizations, 26% fewer inpatient
      bed days, 22% fewer emergency department visits, 44% fewer heart failure
      hospitalizations, 70% fewer 30-day readmissions, and 45% fewer SNF bed days.
      Claims costs were 1,792 dollars per person lower in the intervention group than
      in the control group (inclusive of intervention costs), and the return on
      investment was calculated to be 2.31. CONCLUSION: The study demonstrates that a
      commercially delivered heart failure disease-management program significantly
      reduced hospitalizations, emergency department visits, and SNF days. The
      intervention group had 17% lower costs than the control group; when intervention
      costs were included, the intervention group had 10% lower costs.

PMID- 15450042
TI  - Hyperkyphotic posture predicts mortality in older community-dwelling men and
      women: a prospective study.
AB  - OBJECTIVES: To determine the association between hyperkyphotic posture and rate
      of mortality and cause-specific mortality in older persons. DESIGN: Prospective
      cohort study. SETTING: Rancho Bernardo, California. PARTICIPANTS: Subjects were
      1,353 participants from the Rancho Bernardo Study who had measurements of
      kyphotic posture made at an osteoporosis visit between 1988 and 1991. MEASURES:
      Kyphotic posture was measured as the number of 1.7-cm blocks that needed to be
      placed under the participant's head to achieve a neutral head position when lying
      supine on a radiology table. Demographic and clinical characteristics and health
      behaviors were assessed at a clinic visit using standard questionnaires.
      Participants were followed for an average of 4.2 years, with mortality and cause
      of death confirmed using review of death certificates. RESULTS: Hyperkyphotic
      posture, defined as requiring one or more blocks under the occiput to achieve a
      neutral head position while lying supine, was more common in men than women (44%
      in men, 22% of women, P<.0001). In age- and sex-adjusted analyses, persons with
      hyperkyphotic posture had a 1.44 greater rate of mortality (95% confidence
      interval (CI)=1.12-1.86, P=.005). In multiply adjusted models, the increased rate
      of death associated with hyperkyphotic posture remained significant (relative
      hazard=1.40, 95% CI=1.08-1.81, P=.012). In cause-specific mortality analyses,
      hyperkyphotic posture was specifically associated with an increased rate of death
      due to atherosclerosis. CONCLUSION: Older men and women with hyperkyphotic
      posture have higher mortality rates.

PMID- 15450043
TI  - Detection and management of cognitive impairment in primary care: The Steel
      Valley Seniors Survey.
AB  - OBJECTIVES: To identify characteristics of older primary care patients who were
      cognitively impaired and who underwent mental status testing by their physicians.
      DESIGN: Cross-sectional and retrospective analysis. SETTING: Seven small-town
      primary care practices. PARTICIPANTS: A total of 1,107 patients with a mean+/
      standard deviation age of 76.3+/-6.6, screened using the Mini-Mental State
      Examination (MMSE); medical records reviewed. MEASUREMENTS: Demographics, MMSE,
      medical record information. Odds ratios (OR) with 95% confidence intervals (CI),
      adjusted for age, sex, and education. RESULTS: Thirty-one percent of the sample
      had MMSE scores of less than 25. Among these patients, physicians documented
      memory loss in only 23% which was significantly more often than in the higher
      scoring group (OR=1.9, 95% CI=1.3-2.8), basic activity of daily living (ADL)
      impairment in 7.9% (OR=2.4, 95% CI=1.3-4.4), instrumental ADL (IADL) impairment
      in 6.7% (OR=2.2, 95% CI=1.1=4.2), dementia in 12.2% (OR=3.7, 95% CI=2.0-6.8), and
      prescription of cholinesterase inhibitors in 7.6% (OR=4.4, 95% CI=1.9-10.2).
      Physicians recorded mental status testing largely in patients with research MMSE
      scores of 24 to 28, significantly more often when they also documented memory
      loss (OR=3.8, 95% CI=2.5-5.6) or impaired IADLs (OR=2.7, 95% CI=1.4-5.2),
      diagnosed dementia (OR=4.9, 95% CI=2.8-8.6), referred to specialists (OR=6.3, 95%
      CI=2.5-16.2) or social services (OR=3.6, 95% CI=1.8-7.3), or prescribed
      cholinesterase inhibitors (OR=8.5, 95% CI=4.2-17.5). CONCLUSION: Physicians noted
      impairment in a minority of impaired patients. They tested mental status in those
      with documented cognitive and functional difficulties, in very mildly impaired
      patients, and in those for whom they intervened.

PMID- 15450044
TI  - Geriatric patients improve as much as younger patients from hospitalization on
      general psychiatric units.
AB  - OBJECTIVES: To determine whether geriatric patients aged 65 and older on general
      adult psychiatric units improve as much as younger patients, over what duration
      their improvement occurs, and their risk of readmission. DESIGN: Cohort study.
      SETTING: Inpatient psychiatric unit of an urban, university-affiliated, county
      hospital from January 1993 through August 1999. PARTICIPANTS: A total of 5,929
      inpatients. MEASUREMENTS: Standardized, routine assessments by attending
      psychiatrists included the Psychiatric Symptom Assessment Scale (PSAS) on
      admission and discharge. Discharge scores, length of stay (LOS), and risk of
      readmission within 1 year were modeled for the groups using multiple regression
      analyses. RESULTS: Geriatric patients constituted 5% (n=299) of the 5,929
      admissions. In multivariate analysis, geriatric status was not associated with
      discharge PSAS scores. Median LOS was longer for geriatric patients (16 days)
      than younger patients (10 days, P<.001), especially in older women (14 days) and
      geriatric patients with mild medical illness severity (13 days vs 11 days in
      those with moderate-to-severe medical illness). Geriatric patients were as likely
      to be readmitted within 1 year of discharge as younger patients. CONCLUSION:
      Geriatric patients on general inpatient psychiatry units improved as much as
      younger patients. Their longer LOS was associated with milder medical illness
      severity. There may be a role for more specialized care of elderly women or
      geriatric patients with mild to moderate medical illness to improve the
      efficiency of their care.

PMID- 15450045
TI  - Patterns of presentation, diagnosis, and treatment in older patients with colon
      cancer and comorbid dementia.
AB  - OBJECTIVES: To estimate patterns of colon cancer presentation, diagnosis, and
      treatment according to history of dementia using National Cancer Institute (NCI)
      Surveillance, Epidemiology, and End-Result (SEER) Medicare data. DESIGN:
      Population-level cohort study. SETTING: NCI's SEER-Medicare database.
      PARTICIPANTS: A total of 17,507 individuals aged 67 and older with invasive colon
      cancer (Stage I-IV) were identified from the 1993-1996 SEER file. Medicare files
      were evaluated to determine which patients had an antecedent diagnosis of
      dementia. MEASUREMENTS: Parameters relating to the cohort's patterns of
      presentation and care were estimated using logistic regressions. RESULTS: The
      prevalence of dementia in the cohort of newly diagnosed colon cancer patients was
      6.8% (1,184/17,507). Adjusting for possible confounders, dementia patients were
      twice as likely to have colon cancer reported after death (i.e., autopsy or death
      certificate) (adjusted odds ratio (AOR)=2.31, 95% confidence interval (CI)=1.79
      3.00). Of those diagnosed before death (n=17,049), dementia patients were twice
      as likely to be diagnosed noninvasively than with tissue evaluation (i.e.,
      positive histology) (AOR=2.02 95% CI=1.63-2.51). Of patients with Stage I -III
      disease (n=12,728), patients with dementia were half as likely to receive
      surgical resection (AOR=0.48, 95% CI=0.33-0.70). Furthermore, of those with
      resected Stage III colon cancer (n=3,386), dementia patients were 78% less likely
      to receive adjuvant 5-fluorouracil (AOR=0.22, 95% CI=0.13-0.36). CONCLUSION:
      Although the incidences of dementia and cancer rise with age, little is known
      about the effect of dementia on cancer presentation and treatment. Elderly colon
      cancer patients are less likely to receive invasive diagnostic methods or
      curative-intent therapies. The utility of anticancer therapies in patients with
      dementia merits further study.

PMID- 15450046
TI  - Breast cancer screening in women aged 80 and older: results from a national
      survey.
AB  - OBJECTIVES: To estimate the national rates of mammography screening in women aged
      80 and older and examine the relationship between health status and screening
      within the previous 2 years. DESIGN: Population-based survey. SETTING: United
      States. PARTICIPANTS: Eight hundred eighty-two women aged 80 and older who
      responded to the 2000 National Health Interview Survey, representing an estimated
      3.83 million noninstitutionalized women nationally. MEASUREMENTS: Screening
      mammography, disease burden, and functional status were assessed using a
      questionnaire. RESULTS: Of the 882 women, 41.5% were aged 85 and older; 19.6% had
      two or more significant diseases; and 12.1% were dependent in at least one
      activity of daily living (ADL). More than half (50.8%) had received a screening
      mammogram within the previous 2 years. Women with two or more significant
      diseases were less likely to have received screening than those without
      significant disease, but the difference was not statistically significant (43.9%
      vs 54.0%, P=.152). Women dependent in at least one ADL were less likely to
      receive screening mammography than women without functional impairment (37.2% vs
      55.9%, P<.001). After adjustment, the likelihood of screening remained lower in
      women with two or more significant diseases (adjusted odds ratio (AOR)=0.63, 95%
      confidence interval (CI)=0.40-1.05) and in women with at least one ADL dependency
      (AOR=0.44, 95% CI=0.22-0.88). Of 294 women likely to have life expectancies of
      less than 5 years because of poor health, 39.4% received screening mammography.
      CONCLUSION: More than half of women aged 80 and older in the United States
      receive screening mammograms. Nearly 40% of women very unlikely to benefit
      because of poor health received screening mammography.

PMID- 15450047
TI  - Body weight change and mortality in a cohort of elderly patients recently
      discharged from the hospital.
AB  - OBJECTIVES: To evaluate the prognostic significance of weight change in frail
      elderly patients. DESIGN: Prospective study. SETTING: The general medical or
      surgical wards of a university-affiliated Department of Veterans Affairs
      hospital. PARTICIPANTS: Six hundred sixty randomly selected subjects aged 65 or
      older. MEASUREMENTS: At admission and discharge, each subject completed a
      standardized diagnostic evaluation, including demographic variables, and basic
      medical, functional, and nutritional assessments. Weights were recorded from
      hospital or clinic visits in the year before admission, during the current
      hospitalization, and after discharge for a median of 5.6 years. Average yearly
      intraindividual weight change was calculated using least-squares regression.
      Associations between intraindividual weight change and mortality were identified
      using Cox proportional hazards regression. RESULTS: During the study, 314
      subjects (48%) died. A U-shaped association between weight change and mortality
      was observed. Those who were relatively weight stable (+/-1 kg/y) had the lowest
      mortality (28%). Compared with this group, the adjusted relative risks (ARR) of
      death for those who lost 1 or more to less than 3 kg/y and 3 or more kg/y were
      2.14 (95% confidence interval (CI)=1.52-3.00) and 3.59 (95% CI=2.58-4.99),
      respectively. The ARR associated with a weight gain of 1 or more to less than 3
      kg/y and 3 or more kg/y was 1.38 (95% CI=0.91-2.10) and 3.73 (95% CI=2.34-5.94),
      respectively. The amount of bidirectional weight fluctuation (estimated using
      coefficient of variance) was not significantly associated with mortality.
      CONCLUSION: For reasons that are not clear, elderly patients who gain 3 or more
      kg/y after hospital discharge are at nearly the same risk of mortality as those
      who lose this amount of weight.

PMID- 15450048
TI  - Improvement of weight and fat-free mass with oral nutritional supplementation in
      patients with Alzheimer's disease at risk of malnutrition: a prospective
      randomized study.
AB  - OBJECTIVES: To study the effects of oral nutritional supplements (OS) on body
      weight, body composition, nutritional status, and cognition in elderly patients
      with Alzheimer's disease (AD). DESIGN: Prospective, randomized, controlled study.
      SETTING: Geriatric wards and day care centers in the Toulouse area, France.
      PARTICIPANTS: Ninety-one subjects with AD aged 65 and older at risk of
      undernutrition as evaluated using the Mini Nutritional Assessment. INTERVENTION:
      After randomization, 46 patients (intervention group) received 3-month OS. The
      other 45 patients (control group) received usual care. MEASUREMENTS: Weight, body
      composition (evaluated using dual-energy x-ray absorptiometry), cognitive
      function, activities of daily living, eating behavior, and dietary intakes were
      evaluated at the beginning of the study and at 3 months and 6 months. Supplement
      compliance was recorded each day. RESULTS: Between baseline and 3 months, energy
      and protein intakes significantly improved in the intervention group, resulting
      in a significant increase in weight and fat-free mass, but no significant changes
      were found for dependence, cognitive function, or biological markers. The
      nutritional benefit was maintained in the intervention group after
      discontinuation of OS at 3 months. CONCLUSION: Three-month daily OS significantly
      improves body weight. It is practicable and effective, and the patients accepted
      it well. The improvement that was observed even in the control group showed that
      caregiver education is an important factor in maintaining the nutritional status
      of patients with AD. Moreover, regular courses of OS may help to maintain the
      increase in fat-free mass and improve the nutritional status of these patients.

PMID- 15450049
TI  - Risk factors relating blood markers of inflammation and nutritional status to
      survival in cachectic geriatric patients in a randomized clinical trial.
AB  - OBJECTIVES: To evaluate the effect of proinflammatory cytokines, their receptors,
      and nutritional indicators (at baseline and after 12 weeks of megestrol acetate
      (MA) treatment) upon long-term survival in geriatric cachectic patients without
      active acute infections, inflammation, or cancer. DESIGN: Randomized clinical
      trial with placebo or MA treatment for 12 weeks and then follow-up for more than
      4 years. SETTING: Veterans Affairs nursing home in Northport, New York.
      PARTICIPANTS: Nursing home patients with weight loss of 5% of usual body weight
      over the previous 3 months or body weight 20% below ideal body weight.
      INTERVENTION: Random assignment of placebo or MA oral suspension 800 mg/d to the
      eligible patients for 12 weeks. MEASUREMENTS: White blood cell counts,
      prealbumin, plasma cytokine levels (or their receptors), including tumor necrosis
      factor receptor (TNFR), soluble subunits (TNFR-p55 and TNFR-p75), interleukin
      (IL)-6, soluble IL-2 receptor, and C-reactive protein at baseline and 12 weeks
      after treatment. RESULTS: There was no difference in survival between the MA and
      placebo groups. Considering possible confounders, initial IL-6, initial TNFR-p75
      levels, and final neutrophil percentage were associated with elevated mortality,
      whereas higher initial prealbumin, initial albumin, final prealbumin, final
      albumin, and final weight gain were associated with decreased death. CONCLUSION:
      In geriatric weight-loss patients with cachexia, certain cytokines and
      nutritional indicators were effective in predicting long-term mortality,
      regardless of treatment with MA. Interventions to modify levels of these
      cytokines or their receptors and improvement in nutritional status by weight gain
      might be helpful in ameliorating undetected chronic inflammation and thus might
      prolong the survival of these nursing home residents.

PMID- 15450050
TI  - Insulin resistance and executive dysfunction in older persons.
AB  - OBJECTIVES: To evaluate the association between insulin resistance (IR) and
      executive dysfunction in a large, population-based study of older persons without
      diabetes mellitus (DM) or dementia. DESIGN: Cross-sectional study. SETTING:
      Outpatient clinic in Greve in Chianti and Bagno a Ripoli, Italy. PARTICIPANTS: A
      total of 597 subjects aged 65 to 93 without DM or dementia. MEASUREMENTS:
      Anthropometric measurements; plasma fasting levels of glucose, insulin,
      cholesterol (total cholesterol, high-density lipoprotein cholesterol (HDL-C), low
      density lipoprotein cholesterol), and insulin-like growth factor-1 (IGF-1);
      homeostasis model assessment (HOMA) to estimate degree of IR; Trail Making Test
      (TMT) A; TMT-B; TMT-B minus TMT-A (DIFF B-A); and Mini-Mental State Examination
      (MMSE). RESULTS: IR (HOMA) was associated with longer TMT-B (correlation
      coefficient (r)=0.11; P=.006) and DIFF B-A times (r=0.10; P=.022). Subjects in
      the upper tertile of IR were older and had longer TMT-B and DIFF B-A than
      participants in the lowest tertile. After adjusting for age, sex, and years of
      formal education, IR was significantly correlated with TMT-A, TMT-B, and DIFF B
      A. After adjusting for age, sex, education, body mass index, waist:hip girth
      ratio, HDL-C, triglycerides, IGF-1, hypertension, drug intake, and physical
      activity, the results did not significantly change. After introducing MMSE score
      into the model, IR continued to be an independent determinant of TMT-A
      (beta=11.005; P=.021), TMT-B (beta=28.379; P<.001), and DIFF B-A (beta=17.374;
      P=.011). CONCLUSION: IR is independently associated with frontal cortex function
      evidenced by poor TMT times in older persons without DM or dementia.

PMID- 15450051
TI  - The relationship between number of medications and weight loss or impaired
      balance in older adults.
AB  - OBJECTIVES: To examine the relationship between cumulative medication exposure
      and risk of two common manifestations of adverse drug effects: weight loss and
      impaired balance. DESIGN: Cross-sectional and longitudinal cohort. SETTING: Urban
      Connecticut community. PARTICIPANTS: Eight hundred eighty-five community-dwelling
      residents aged 72 and older. MEASUREMENTS: Weight loss (> or =10 pounds) and
      balance, a composite of four balance measures. RESULTS: Participants took a
      mean+/-standard deviation of 2.2+/-1.9 medications (range 0-15). After adjustment
      for age, depressive symptoms, cognitive impairment, vision and hearing
      impairments, number of chronic diseases, and number of hospitalizations in the
      previous year, the adjusted odds ratio (OR) for weight loss was 1.48 (95%
      confidence interval (CI)=0.85-2.59) for those taking one to two medications, 1.96
      (95% CI=1.08-3.54) for three to four medications, and 2.78 (95% CI=1.38-5.60) for
      five or more medications. For impaired balance, adjusted ORs were 1.44 (95%
      CI=0.94-2.19), 1.72 (95% CI=1.09-2.71), and 1.80 (95% CI=1.02-3.19),
      respectively. CONCLUSION: A greater number of medications were associated with
      increased risk of adverse drug outcomes, after extensive adjustment for chronic
      illness. Clinicians should consider the adverse effects of total drug use and not
      merely the benefits or risks of individual medications for specific diseases.

PMID- 15450052
TI  - The development of a rapid screen for caregiver burden.
AB  - OBJECTIVES: To develop a shortened screen for burden associated with caring for a
      patient with Alzheimer's disease (AD). DESIGN: Cross-sectional. SETTING: The
      Memory Disorders Clinic of an AD center. PARTICIPANTS: Two hundred fifty-one AD
      patient-caregiver dyads. MEASUREMENTS: Screen for Caregiver Burden (SCB), Center
      for Epidemiologic Studies Depression scale, Medical Outcomes Short Form, Mini
      Mental State Examination, and patient and caregiver characteristics. RESULTS: At
      least 25% of the sample endorsed eight of the 25 items in the SCB subjective
      burden (SB) scale. Of these eight items with a prevalence of 25% or greater
      endorsement, seven items had item-total correlations of 0.55 or greater. The
      shortened seven-item SCB SB had an alpha of 0.86, indicating that the shortened
      scale has good internal consistency (Full SCB SB alpha=0.88). The seven-item SCB
      SB was highly associated with depression and overall mental health measures.
      CONCLUSION: This shortened version of the SCB allows a clinician to rapidly
      assess the burden associated with caregiving for a person with AD.

PMID- 15450053
TI  - Nursing home characteristics and potentially preventable hospitalizations of long
      stay residents.
AB  - OBJECTIVES: To examine the association between having a nurse
      practitioner/physician assistant (NP/PA) on staff, other nursing home (NH)
      characteristics, and the rate of potentially preventable/avoidable
      hospitalizations of long-stay residents, as defined using a list of ambulatory
      care-sensitive (ACS) diagnoses. DESIGN: Cross-sectional prospective study using
      Minimum Data Set (MDS) assessments, Centers for Medicare and Medicaid Services
      inpatient claims and eligibility records, On-line Survey Certification Automated
      Records, (OSCAR) and Area Resource File (ARP). SETTING: Freestanding urban NHs in
      Maine, Kansas, New York, and South Dakota. PARTICIPANTS: Residents of 663
      facilities with a quarterly or annual MDS assessment in the 2nd quarter of 1997,
      who had a prior MDS assessment at least 160 days before, and who were not health
      maintenance organization members throughout 1997 (N=54,631). MEASUREMENTS: A 180
      day multinomial outcome was defined as having any hospitalization with primary
      ACS diagnosis, otherwise having been hospitalized, otherwise died, and otherwise
      remained in the facility. RESULTS: Multilevel models show that facilities with
      NP/PAs were associated with lower hospitalization rates for ACS conditions
      (adjusted odds ratio (AOR)=0.83), but not with other hospitalizations. Facilities
      with more physicians were associated with higher ACS hospitalizations (ACS,
      AOR=1.14, and non-ACS, AOR=1.10). Facilities providing intravenous therapy, and
      those that operate a nurses' aide training program were associated with fewer
      hospitalizations of both types. CONCLUSION: Employment of NP/PAs in NHs, the
      provision of intravenous therapy, and the operation of certified nurse assistant
      training programs appear to reduce ACS hospitalizations, and may be feasible cost
      saving policy interventions.

PMID- 15450054
TI  - Effect of antipsychotic withdrawal on behavior and sleep/wake activity in nursing
      home residents with dementia: a randomized, placebo-controlled, double-blinded
      study. The Bergen District Nursing Home Study.
AB  - OBJECTIVES: To explore the effect on sleep/wake activity and on behavioral and
      psychological symptoms of the withdrawal of antipsychotic medications from
      nursing home (NH) patients with dementia. DESIGN: Randomized, placebo-controlled,
      double-blind trial. SETTING: NHs in Bergen, Norway. PARTICIPANTS: Thirty patients
      (mean age 83.5) taking haloperidol, risperidone, or olanzapine for nonpsychotic
      symptoms. INTERVENTION: Study participants were randomly assigned to withdrawal
      (intervention group) or continued treatment with antipsychotic medications
      (reference group) for 4 consecutive weeks. MEASUREMENTS: Behavioral rating using
      the Neuropsychiatric Inventory Questionnaire (NPI-Q) and actigraphy. RESULTS:
      After antipsychotic withdrawal, behavioral scores remained stable or improved in
      11 of 15 patients, whereas four had worsening scores. Actigraphy revealed
      decreased sleep efficiency after drug discontinuation and increased 24-hour and
      night activity in both groups. Actigraphy records of nighttime and daytime
      activity indicated sleep problems and restlessness, in terms of the NPI-Q. One
      patient was restarted on antipsychotics. CONCLUSION: Antipsychotic drug
      withdrawal affected activity and sleep efficiency over the short term. Increases
      in total activity and impaired sleep quality after drug discontinuation should be
      monitored, because the long-term effect of these changes is not known. The NPI-Q
      and actigraphy are feasible tools that disclose relevant changes occurring during
      antipsychotic withdrawal in NH patients with dementia. Their use in clinical
      practice should be substantiated by larger studies.

PMID- 15450055
TI  - The delirium index, a measure of the severity of delirium: new findings on
      reliability, validity, and responsiveness.
AB  - OBJECTIVES: To assess the reliability, validity, and responsiveness of an
      instrument for measuring the severity of delirium, the Delirium Index (DI).
      DESIGN: Prospective cohort study, with repeated patient assessments at multiple
      points in the hospital, at 8 weeks after discharge, and at 6 and 12 months after
      admission. SETTING: The medical services of a primary acute-care hospital.
      PARTICIPANTS: Medical admissions aged 65 and older: 165 with delirium and
      dementia, 57 with delirium only, 55 with dementia only, and 41 with neither.
      MEASUREMENTS: Severity of delirium symptoms was measured using the DI. Delirium
      was diagnosed using the Confusion Assessment Method. Other measures included the
      Mini-Mental State Examination, Informant Questionnaire on Cognitive Decline in
      the Elderly, Barthel Index (BI), premorbid instrumental activities of daily
      living, Charlson Comorbidity Index, Clinical Severity of Illness scale (CSI), and
      the Acute Physiology Score (APS). RESULTS: The intraclass correlation coefficient
      of interrater reliability was 0.98. Two measures of fluctuation were
      significantly higher in patients with delirium than in those without delirium. At
      baseline, the DI was correlated with the BI, APS, and CSI in delirious patients
      with (correlation coefficient (r)=-0.43, 0.17, and 0.36, respectively) or without
      (r=-0.44, 0.39, 0.22, respectively) dementia. At 8 weeks, in delirious patients
      with and without dementia, internal responsiveness as measured by effect sizes
      was -0.60 and -0.74, respectively, and the standardized response mean for both
      groups was -0.64. Low to good levels of external responsiveness were found.
      CONCLUSION: The DI appears to be a reliable, valid, and responsive measure of the
      severity of delirium, in patients with delirium, with or without dementia.

PMID- 15450056
TI  - Association between subject functional status, seat height, and movement strategy
      in sit-to-stand performance.
AB  - OBJECTIVES: To explore the association between an individual's functional status,
      movement task difficulty, and effectiveness of compensatory movement strategies
      within a sit-to-stand (STS) paradigm. DESIGN: Cross-sectional study. SETTINGS:
      Rehabilitation unit of the Istituto Nazionale Riposo e Cura Anziani Geriatric
      Hospital of Florence, Italy. PARTICIPANTS: A convenience sample (131 subjects) of
      the outpatient clinic and day-hospital population. MEASUREMENTS: A performance
      based test (repeated chair standing) was used to divide the subjects into five
      functional groups. Subjects performed a series of single STS tasks across a range
      of five descending seat heights. They were instructed to stand without using arms
      or compensatory strategies. If unable, swinging the arms was allowed, and if the
      inability persisted, subjects could push with their arms during subsequent
      attempts. The strategy or inability to stand formed the dependent measures.
      RESULTS: Subjects within the two highest functional groups could complete the
      single STS task at all seat heights, with a slight increased use of compensatory
      strategies at the lowest seat height. The effectiveness of the compensatory
      strategies decreased rapidly as a function of seat height and functional status.
      One-third (35.5%) of the subjects in the middle functional group swung their arms
      at the lower seat heights. Across the three least functional groups, 11.8%,
      30.6%, and 83.3% of the subjects, respectively, were unable to stand at the
      lowest seat height. CONCLUSION: The individual's functional status and difficulty
      of the task influenced the effectiveness of a compensatory strategy to maintain
      the ability to stand, supporting the idea that disability depends on the
      interplay between environmental demands and physical ability.

PMID- 15450057
TI  - History, development, and future of the progressively lowered stress threshold: a
      conceptual model for dementia care.
AB  - Behavioral symptoms associated with dementia are a major concern for the person
      who experiences them and for caregivers who supervise, support, and assist them.
      The knowledge and skill of formal and informal caregivers affects the quality of
      care they can provide and their ability to cope with the challenges of
      caregiving. Nurses are in an excellent position to provide training to empower
      caregivers with the knowledge and skills necessary to reduce and better manage
      behaviors. This article reviews advances in geriatric nursing theory, practice,
      and research based on the Progressively Lowered Stress Threshold (PLST) model
      that are designed to promote more adaptive and functional behavior in older
      adults with advancing dementia. For more than 17 years, the model has been used
      to train caregivers in homes, adult day programs, nursing homes, and acute care
      hospitals and has served as the theoretical basis for in-home and institutional
      studies. Care planning principles and key elements of interventions that flow
      from the model are set forth, and outcomes from numerous research projects using
      the PLST model are presented.

PMID- 15450058
TI  - Health care for older persons in Argentina: a country profile.
AB  - Argentina is a large country situated at the southern end of the Americas. It is
      highly urbanized, and almost one-third of the population lives in the capital
      city and its surrounding area (Buenos Aires). The population is composed of
      heterogeneous groups, formed primarily by descendants of European immigration who
      constitute 85% of the inhabitants. In the last 30 years, Argentina has witnessed
      a growth in the elderly population from less than 7% to nearly 10% of the total
      population. Additionally, in Buenos Aires City, more than 17% are aged 65 or
      older. The healthcare systems for the elderly lack nationwide coverage. The
      Programa de Atencion Medica Integral (PAMI) is the largest program for elderly
      care. It is a state-run program for disabled and senior citizens. PAMI serves 65%
      of the approximately 3.6 million older people in Argentina. The quality of PAMI
      healthcare delivery has decreased in the last 2 decades and has largely declined
      since the Argentinean economic crisis of late 2001. The rehabilitation and long
      term care services are relatively underdeveloped, and fewer than 2% of senior
      citizens live in residential or nursing homes. Recently, the government has
      proposed a system of care built up from the primary care resources of the
      community.

PMID- 15450060
TI  - The importance of geriatric-specific instruments and functional status assessment
      in infectious diseases research: time to start preaching to the congregation
      instead of the choir.

PMID- 15450061
TI  - Care of dementia and other mental disorders in assisted living facilities: new
      research and borrowed knowledge.

PMID- 15450062
TI  - Progressively lowered stress threshold model: understanding behavioral symptoms
      of dementia.

PMID- 15450064
TI  - Combined use of fasting glucose and hemoglobin a levels in screening for new type
      2 diabetes mellitus in elderly men: TCVGHAGE.

PMID- 15450065
TI  - Type 2 diabetes mellitus as a risk factor for hip fracture.

PMID- 15450066
TI  - A case of cutaneous horn in a 99-year-old woman.

PMID- 15450067
TI  - Do older people tolerate ambulatory blood pressure monitoring?

PMID- 15450068
TI  - A clinicopathological study of rest tremors in the elderly.

PMID- 15450069
TI  - An 85-year-old Japanese woman with Philadelphia chromosome-positive chronic
      myelogenous leukemia with del (5q) successfully treated by intermittent imatinib
      therapy.

PMID- 15450070
TI  - Buformin-induced lactic acidosis--a symptom of modern healthcare malady.

PMID- 15450071
TI  - Retroperitoneal abscess after sphincterotomy-related perforation.

PMID- 15450072
TI  - Gustatory rhinorrhea as a complication of oral surgery.

PMID- 15450073
TI  - Theophylline-improved swallowing reflex in elderly nursing home patients.

PMID- 15450074
TI  - Ertapanem therapy for community-acquired pneumonia in the elderly.

PMID- 15450076
TI  - A disaccharide derived from chondroitin sulphate proteoglycan promotes central
      nervous system repair in rats and mice.
AB  - Chondroitin sulphate proteoglycan (CSPG) inhibits axonal regeneration in the
      central nervous system (CNS) and its local degradation promotes repair. We
      postulated that the enzymatic degradation of CSPG generates reparative products.
      Here we show that an enzymatic degradation product of CSPG, a specific
      disaccharide (CSPG-DS), promoted CNS recovery by modulating both neuronal and
      microglial behaviour. In neurons, acting via a mechanism that involves the
      PKCalpha and PYK2 intracellular signalling pathways, CSPG-DS induced neurite
      outgrowth and protected against neuronal toxicity and axonal collapse in vitro.
      In microglia, via a mechanism that involves ERK1/2 and PYK2, CSPG-DS evoked a
      response that allowed these cells to manifest a neuroprotective phenotype ex
      vivo. In vivo, systemically or locally injected CSPG-DS protected neurons in mice
      subjected to glutamate or aggregated beta-amyloid intoxication. Our results
      suggest that treatment with CSPG-DS might provide a way to promote post-traumatic
      recovery, via multiple cellular targets.

PMID- 15450077
TI  - The contribution of activated phagocytes and myelin degeneration to axonal
      retraction/dieback following spinal cord injury.
AB  - Myelin-derived molecules inhibit axonal regeneration in the CNS. The Long-Evans
      Shaker rat is a naturally occurring dysmyelinated mutant, which although able to
      express the components of myelin lacks functional myelin in adulthood. Given that
      myelin breakdown exposes axons to molecules that are inhibitory to regeneration,
      we sought to determine whether injured dorsal column axons in a Shaker rat would
      exhibit a regenerative response absent in normally myelinated Long-Evans
      (control) rats. Although Shaker rat axons did not regenerate beyond the lesion,
      they remained at the caudal end of the crush site. Control rat axons, in
      contrast, retracted and died back from the edge of the crush. The absence of
      retraction/dieback in Shaker rats was associated with a reduced phagocytic
      reaction to dorsal column crush around the caudal edge of the lesion. Systemic
      injection of minocycline, a tetracycline derivative, in control rats reduced both
      the macrophage response and axonal retraction/dieback following dorsal column
      injury. In contrast, increasing macrophage activation by spinal injection of the
      yeast particulate zymosan had no effect on axonal retraction/dieback in Shaker
      rats. Schwann cell invasion was reduced in minocycline-treated control rats
      compared with untreated control rats, and was almost undetectable in Shaker rats,
      suggesting that like axonal retraction/dieback, spinal Schwann cell infiltration
      is dependent upon macrophage-mediated myelin degeneration. These results indicate
      that following spinal cord injury the phagocyte-mediated degeneration of myelin
      and subsequent exposure of inhibitory molecules to the injured axons contributes
      to their retraction/dieback.

PMID- 15450078
TI  - Recovery of bimodal locomotion in the spinal-transected salamander, Pleurodeles
      waltlii.
AB  - Electromyographic (EMG) analysis was used to provide an assessment of the
      recovery of locomotion in spinal-transected adult salamanders (Pleurodeles
      waltlii). EMG recordings were performed during swimming and overground stepping
      in the same animal before and at various times (up to 500 days) after a mid-trunk
      spinalization. Two-three weeks after spinalization, locomotor EMG activity was
      limited to the forelimbs and the body rostral to the transection. Thereafter,
      there was a return of the locomotor EMG activity at progressively more caudal
      levels below the transection. The animals reached stable locomotor patterns 3-4
      months post-transection. Several locomotor parameters (cycle duration, burst
      duration, burst proportion, intersegmental phase lag, interlimb coupling)
      measured at various recovery times after spinalization were compared with those
      in intact animals. These comparisons revealed transient and long-term alterations
      in the locomotor parameters both above and below the transection site. These
      alterations were much more pronounced for swimming than for stepping and revealed
      differences in adaptive plasticity between the two locomotor networks. Recovered
      locomotor activity was immediately abolished by retransection at the site of the
      original spinalization, suggesting that the spinal cord caudal to the transection
      was reinnervated by descending brain and/or propriospinal axons, and that this
      regeneration contributed to the restoration of locomotor activity. Anatomical
      studies conducted in parallel further demonstrated that some of the regenerated
      axons came from glutamatergic and serotoninergic immunoreactive cells within the
      reticular formation.

PMID- 15450079
TI  - Functional recovery and axonal growth following spinal cord transection is
      accelerated by sustained L-DOPA administration.
AB  - The eel, Anguilla anguilla, as with other fish species, recovers well from spinal
      cord injury. We assessed the quality of locomotion of spinally transected eels
      from measurements made from video recordings of individuals swimming at different
      speeds in a water tunnel. Following transection of the spinal cord just caudal to
      the anus, the animals displayed higher tail beat frequencies and lower tail beat
      amplitudes than before surgery, owing to the loss of power in this region.
      Swimming performance then progressively recovered, appearing normal within 1
      month of surgery. Eels with similar transections, but given regular, repeated
      intraperitoneal injections (50 mg/kg) of l-3,4-dihydroxyphenylalanine (L-DOPA)
      showed an equivalent pattern of decline and recovery that was 10-20 days shorter
      than that seen in non-treated fish. Axonal growth into the denervated cord, as
      determined from anterograde labelling experiments, was also more rapid in the
      drug-treated fish. L-DOPA treatment increased the activity of all fish for up to
      18 h, and accelerated the spontaneous movements ('spinal swimming') made by the
      denervated, caudal portion of the animal that appeared following transection. We
      suggest that this enhancement of locomotion underlies the accelerated axonal
      growth and, hence, functional recovery.

PMID- 15450080
TI  - Axon-dominant localization of cell-surface cholesterol in cultured hippocampal
      neurons and its disappearance in Niemann-Pick type C model cells.
AB  - There is growing evidence showing the important role of cholesterol in
      maintaining neuronal function. In particular, much attention has been paid to the
      role of the cholesterol-rich microdomains called lipid rafts. However, the
      cholesterol distribution on neurons is not clear. Here, we investigated
      localization of cholesterol in cultured rat hippocampal neurons, using filipin
      and a novel cholesterol-binding reagent BCtheta. In our culture system, BCtheta
      detects only cell-surface cholesterol, whereas filipin stains both intracellular
      and cell-surface cholesterol. BCtheta staining appeared visible in a maturation
      dependent manner and showed axon-dominant distribution of cell-surface
      cholesterol in fully matured neurons. A part of this cholesterol on axons was
      resistant to detergents at 4 degrees C, and thus might be involved in lipid
      rafts. Interestingly, Niemann-Pick type C model neurons induced by class 2
      amphiphiles lost the cell-surface but not the intracellular cholesterol staining.
      Niemann-Pick type C disease is caused by the disruption of intracellular
      cholesterol transport and is known to induce neurodegeneration in brains
      accompanied by formation of neurofibrillary tangles. Our observations suggest the
      important role of cell-surface cholesterol in maintaining a functional axonal
      membrane and indicate that the observed defect in axonal surface cholesterol
      might lead to neurodegeneration.

PMID- 15450081
TI  - Critical role of the C-terminal segment in the maturation and export to the cell
      surface of the homopentameric alpha 7-5HT3A receptor.
AB  - Many neurological pathologies are related to misfolded proteins. During folding
      and assembly in the endoplasmic reticulum, the nicotinic acetylcholine receptor
      (nAChR) subunits undergo several conformational changes to acquire the ability to
      bind ligands. After folding and maturation, by mechanisms largely unknown,
      receptors are exported to the cell surface. We investigated the maturational role
      of the extracellular C-terminal segment located at the boundary between the
      extracellular and the transmembrane domains. In the functional chimeric alpha7
      5HT3A receptor used as a model system, amino acids from the C-terminal segment
      were successively deleted or mutated. Upon progressive shortening of the peptide
      we observed less and less alpha-bungarotoxin binding sites until no sites could
      be detected when the entire peptide had been deleted (chimera Del 5). Protein
      synthesis and pentameric assembly were not altered. In Del 5 transfected cells,
      pentameric receptors present in the endoplasmic reticulum were not detected on
      the cell surface where Del 5 proteins appeared as patches. With the Del 5
      chimera, export of proteins to the cell surface diminished to about half that of
      wild-type. We propose that the C-terminal segment plays a double role: (i)
      through an interaction between the penultimate tyrosine residue of the C-terminal
      segment and the Cys loop of the N-terminal domain, it locks the receptor in a
      mature alpha-bungarotoxin binding conformation; (ii) this mature conformation, in
      turn, masks a retention signal present in the first transmembrane segment
      allowing properly assembled and matured receptors to escape to the cell surface.

PMID- 15450082
TI  - Bone morphogenetic proteins regulate ionotropic glutamate receptors in human
      retina.
AB  - Bone morphogenetic proteins (BMPs) are required for the development of retina,
      but their role in the mature eye is unknown. We therefore examined the expression
      of BMP-7 in adult human retina and assessed its effects on horizontal cells
      cultured from adult human retina. BMP-7 expression was detected in all retinal
      layers, with high levels of expression being present in the inner and outer
      nuclear layers. Human horizontal cells, found in the inner nuclear layer, possess
      both AMPA and kainate receptors, and glutamatergic agonists that activate these
      receptors induce prominent inward currents. Exposure to BMP-7 suppresses the
      kainate receptor current but enhances the AMPA receptor current. BMP-6, activin,
      and cartilage-derived morphogenic protein-2 (CDMP-2) have similar effects to BMP
      7 and act just as rapidly (< 1 s). In contrast BMP-2 and transforming growth
      factor-beta2 are inactive. The actions of BMP-7 on both AMPA and kainate
      receptors were blocked by the nonselective kinase inhibitor, staurosporine. In
      contrast, the serine/threonine kinase inhibitors blocked only the effects of BMP
      7 on the AMPA current. Thus, BMPs rapidly and differentially regulate two
      ionotropic glutamate receptors through distinct pathways, neither of which
      involves nuclear regulatory activity. These observations suggest that BMPs might
      modify synaptic function in the mature nervous system.

PMID- 15450083
TI  - Reduction in endogenous parkin levels renders glial cells sensitive to both
      caspase-dependent and caspase-independent cell death.
AB  - Mutations in the parkin gene give rise to a familial form of Parkinson's disease,
      autosomal recessive juvenile Parkinsonism (AR-JP). Although the exact mechanisms
      are unclear, it is thought that these 'loss-of-function' mutations contribute to
      the pathological process by interfering with parkin's E3 ubiquitin ligase
      activity. In order to mimic the in vivo loss-of-function, we produced tet
      inducible glial cell lines that, in the presence of doxycycline, were able either
      to under- or to over-express the parkin protein. Using this cell-culture system,
      we found that the induced alteration of parkin levels in glial cell lines caused
      different responses compared with their un-induced counterparts under conditions
      of stress (staurosporine, hydrogen peroxide and dopamine). In particular,
      reduction in the levels of parkin within the transfected cells rendered them more
      susceptible to both apoptotic and necrotic cell death. Interestingly, blocking
      the cell death pathway with caspase inhibitors rescued the cells under-expressing
      parkin from only some of the stress-induced death. These findings implicate a
      pathogenic role of glial cells in the pathogenesis of AR-JP caused by mutations
      in the parkin gene.

PMID- 15450084
TI  - 12-Lipoxygenase plays a key role in cell death caused by glutathione depletion
      and arachidonic acid in rat oligodendrocytes.
AB  - Oxidative injury to premyelinating oligodendrocytes (preOLs) in developing white
      matter has been implicated in the pathogenesis of periventricular leukomalacia,
      the lesion underlying most cases of cerebral palsy in premature infants. In this
      study, we investigated the pathways of OL death induced by intracellular
      glutathione (GSH) depletion. We found that the lipoxygenase (LOX) inhibitors AA
      861 and BMD-122 (N-benzyl-N-hydroxy-5-phenylpentamide; BHPP), but not the
      cyclooxygenase (COX) inhibitor indomethacin, fully protected the cells from GSH
      depletion caused by cystine deprivation. Arachidonic acid (AA), the substrate for
      12-LOX, potentiated the toxicity of mild cystine deprivation and at higher
      concentration was itself toxic. This toxicity was also blocked by 12-LOX
      inhibitors. Consistent with a role for 12-LOX in the cell death pathway, 12-LOX
      activity increased following cystine deprivation in OLs. Blocking 12-LOX with AA
      861 effectively inhibited the accumulation of reactive oxygen species (ROS)
      induced by cystine deprivation. These data suggest that, in OLs, intracellular
      GSH depletion leads to activation of 12-LOX, ROS accumulation and cell death.
      Mature OLs were more resistant than preOLs to cystine deprivation. The difference
      in sensitivity was not due to a difference in 12-LOX activity but rather appeared
      to be related to the presence of stronger antioxidant defense mechanisms in
      mature OLs. These results suggest that 12-LOX activation plays a key role in
      oxidative stress-induced OL death.

PMID- 15450085
TI  - Thyroid hormone participates in the regulation of neural stem cells and
      oligodendrocyte precursor cells in the central nervous system of adult rat.
AB  - Oligodendrocyte development and myelination are under thyroid hormone control. In
      this study we analysed the effects of chronic manipulation of thyroid status on
      the expression of a wide spectrum of oligodendrocyte precursor cells (OPCs)
      markers and myelin basic protein (MBP) in the subventricular zone (SVZ),
      olfactory bulb and optic nerve, and on neural stem cell (NSC) lineage in adult
      rats. Hypo- and hyperthyroidism were induced in male rats, by propyl-thio-uracil
      (PTU) and L-thyroxin (T4) treatment, respectively. Hypothyroidism increased and
      hyperthyroidism downregulated proliferation in the SVZ and olfactory bulb (Ki67
      immunohistochemistry and Western blotting, bromodeoxyuridine uptake). Platelet
      derived growth factor receptor alpha (PDGFalpha-R) and MBP mRNA levels decreased
      in the optic nerve of hypothyroid rats; the same also occurred at the level of
      MBP protein. Hyperthyroidism slightly upregulates selected markers such as NG2 in
      the olfactory bulb. The lineage of cells derived from primary cultures of NSC
      prepared from the forebrain of adult hypo- and hyperthyroid also differs from
      those derived from control animals. Although no difference of in vitro
      proliferation of NSCs was observed in the presence of epidermal growth factor,
      maturation of oligodendrocytes (defined by process number and length) was
      enhanced in hyperthyroidism, suggesting a more mature state than in control
      animals. This difference was even greater when compared with the hypothyroid
      group, the morphology of which suggested a delay in differentiation. These
      results indicate that thyroid hormone affects NSC and OPC proliferation and
      maturation also in adulthood.

PMID- 15450086
TI  - The beta-amyloid precursor protein controls a store-operated Ca2+ entry in
      cortical neurons.
AB  - A polyclonal antibody (APP-Ab) raised against the extracellular domain of the
      beta-amyloid precursor protein (APP) triggers a marked neuronal cell death
      preceded by activation of Ca(2+)-dependent enzymes, neurite degeneration,
      oxidative stress and nuclear condensation [Mbebi et al. (2002) J. Biol. Chem.,
      277, 20979-20990]. We have investigated whether activation of APP by this
      antibody could promote cell death through cellular Ca2+ homeostasis alteration.
      We carried out time-lapse recordings of intracellular Ca2+ signals in cultured
      mice cortical neurons by means of a scanning confocal microscope. When applied in
      the presence of 2 mm external Ca2+, APP-Ab elicited a long-lasting elevation of
      the intracellular concentration of Ca2+ ([Ca2+]i). Experiments performed in the
      absence of external Ca2+ showed that APP-Ab triggers the release of Ca2+ from
      intracellular stores. The re-admission of external Ca2+ provides an additional
      rise of Ca2+ most likely through store-operated channels. A pretreatment of the
      cells with pertussis toxin, to inhibit the activity of Gi/Go proteins, or with
      the phospholipase C inhibitor, 3-nitrocoumarin, prevented both the APP-dependent
      elevation of Ca2+ as well as the APP-Ab-mediated cell death. Similarly, the store
      operated channel inhibitors, 2-APB or SKF-96365 block both the APP-Ab-dependent
      Ca2+ entry and the APP-Ab-mediated cell death. Altogether, our data provide
      functional evidence that APP can perturb intracellular Ca2+ homeostasis by
      emptying intracellular Ca2+ stores and triggering Ca2+ entry through store
      operated channels. In response to APP activation, the long-lasting elevation of
      [Ca2+]i due to an entry of Ca2+ via store-operated channels appears as a major
      event that leads to neuronal cell death.

PMID- 15450087
TI  - Presynaptic muscarinic acetylcholine receptors suppress GABAergic synaptic
      transmission in the intermediate grey layer of mouse superior colliculus.
AB  - The intermediate grey layer (the stratum griseum intermediale; SGI) of the
      superior colliculus (SC) receives cholinergic inputs from the parabrachial region
      of the brainstem. It has been shown that cholinergic inputs activate nicotinic
      acetylcholine (nACh) receptors on projection neurons in the SGI. Therefore, it
      has been suggested that they facilitate the initiation of orienting behaviours.
      In this study, we investigated the effect of muscarinic acetylcholine (mACh)
      receptor activation on GABAergic synaptic transmission to SGI neurons using the
      whole-cell patch-clamp recording technique in slice preparations from mice. The
      GABAA receptor-mediated inhibitory postsynaptic currents (IPSCs) evoked in SGI
      neurons by focal electrical stimulation were suppressed by bath application of 10
      microm muscarine chloride. During muscarine application, both the paired-pulse
      facilitation index and the coefficient of variation of IPSCs increased; however,
      the current responses induced by a transient pressure application of 1 mm GABA
      were not affected by muscarine. Muscarine reduced frequencies of miniature IPSCs
      (mIPSCs) while the amplitudes of mIPSCs remained unchanged. These results
      suggested that mAChR-mediated inhibition of IPSCs was of presynaptic origin. The
      suppressant effect of muscarine was antagonized by an M1 receptor antagonist,
      pirenzepine dihydrochloride (1 microM), and a relatively specific M3 receptor
      antagonist, 4-DAMP methiodide (50 nM). By contrast, an M2 receptor antagonist,
      methoctramine tetrahydrochloride (10 microM), was ineffective. These results
      suggest that the cholinergic inputs suppress GABAergic synaptic transmission to
      the SGI neurons at the presynaptic site via activation of M1 and, possibly, M3
      receptors. This may be an additional mechanism by which cholinergic inputs can
      facilitate tectofugal command generation.

PMID- 15450088
TI  - Tyrosine hydroxylase-positive neurons intrinsic to the human striatum express the
      transcription factor Nurr1.
AB  - The putative dopaminergic (DA) neurons intrinsic to human striatum were studied
      to determine their similarity with DA neurons of the substantia nigra pars
      compacta (SNpc). The comparison was based on morphological features and on the
      presence or absence of Nurr1, an orphan receptor of the nuclear receptor family
      that is essential for the expression of DA phenotype by developing SNpc neurons.
      Immunohistochemistry for the neuronal nuclear protein (NeuN; a neuronal marker)
      and in situ hybridization for tyrosine hydroxylase (TH) and/or Nurr1 were applied
      to post-mortem tissue obtained from seven normal individuals. On one hand, the TH
      positive multipolar neurons in the human striatum, which were subdivided into
      three groups according to their size and pattern of dendritic arborization, were
      found to be morphologically similar to TH-positive neurons of the SNpc. The
      distribution frequency of striatal TH-positive neurons, according to their
      diameter, closely matches the frequency observed for multipolar TH-positive cells
      in the SNpc. On the other hand, the proportion of neurons expressing Nurr1 and TH
      mRNA transcripts on single striatal section was similar to the proportion of TH
      immunoreactive neurons observed on adjacent sections. More importantly, in each
      striatum analysed, virtually all cells that stained for TH also expressed NeuN
      and Nurr1. This study provides novel data that confirm the existence of DA
      neurons intrinsic to the human striatum. It also provides the first evidence for
      the existence of striking morphological and chemical similarities between the DA
      neurons present at striatal level and those that populate the SNpc.

PMID- 15450089
TI  - Haemorrhage-evoked decompensation and recompensation mediated by distinct
      projections from rostral and caudal midline medulla in the rat.
AB  - The haemodynamic response to blood loss consists of three phases: (i) an initial
      compensatory phase during which resting arterial pressure is maintained; (ii) a
      decompensatory phase characterized by a sudden, life-threatening hypotension and
      bradycardia; and (iii) if blood loss ceases, a recompensatory phase during which
      arterial pressure returns to normal. Previous research indicates that
      topographically distinct, rostral and caudal parts of the caudal midline medulla
      (CMM) contain neurons that differentially regulate the timing and magnitude of
      each of the three phases. Specifically, decompensation depends critically on the
      integrity of the rostral CMM; whereas compensation and recompensation depend upon
      the integrity of the caudal CMM. This study aimed to determine, using retrograde
      and anterograde tracing techniques, if the rostral and caudal CMM gave rise to
      different sets of projections to the major cardiovascular region of the
      ventrolateral medulla (VLM) and spinal cord. It was found that rostral and caudal
      CMM each have projections of varying density to the region containing bulbospinal
      (presympathetic) motor neurons in the rostral VLM and preganglionic sympathetic
      motor neurons in the intermediolateral cell column of the spinal cord. Via these
      projections vasomotor tone and hence arterial pressure can be regulated. More
      strikingly: (i) consistent with a role in mediating bradycardia during
      decompensation, the rostral CMM projects uniquely to VLM regions containing vagal
      cardiac motor neurons; and (ii) consistent with its role in mediating
      recompensation, the caudal CMM projects uniquely onto tyrosine hydroxylase
      containing, caudal VLM (A1) neurons whose activity mediates vasopressin release,
      on which recompensation depends.

PMID- 15450090
TI  - Cascades of response vectors of olfactory receptor neurons in Xenopus laevis
      tadpoles.
AB  - Olfactory receptor neurons (ORNs) of Xenopus laevis tadpoles respond to water
      born stimuli such as amino acids. Their sensitivity spectra with respect to amino
      acids have recently been shown to become more selective over ontogenetic stages
      [Manzini & Schild (2004) J. Gen. Physiol., 123, 99-107]. In this paper, we
      undertake a theoretical analysis of this data set and determine the correlational
      relationships among odorant responses represented as binary response vectors. We
      first show that, on the one hand, the number of 204 ORN classes (out of 283
      recorded ORNs) cannot be explained by a random expression pattern of olfactory
      receptors (ORs). On the other hand, this number does not appear to be
      reconcilable with the idea that individual ORNs express one type of OR each. The
      covariance matrix of stimulus responses shows that the responses to some stimuli
      are correlated to those of others. Furthermore, the response vectors show
      positive as well as negative correlations among each other. While the positive
      correlations can partly be explained by the differing response frequencies to the
      odorants used, the negative ones cannot. Finally, we analyse the similarity among
      responses using the Hamming distance as a distance measure, the result being that
      most response vectors differ from others by small Hamming distances. Such vectors
      are shown to form pattern cascades, possibly reflecting a decreasing number of
      ORs being expressed over ontogenetic stages.

PMID- 15450091
TI  - Nitric oxide increases the spontaneous firing rate of rat medial vestibular
      nucleus neurons in vitro via a cyclic GMP-mediated PKG-independent mechanism.
AB  - The effects of nitric oxide (NO) on the discharge rate of medial vestibular
      nucleus neurons (MVNn) were investigated in rat brainstem slices. The NO-donor
      sodium nitroprusside (SNP, 200 microM) caused a marked enhancement (+36.7%) of
      MVNn spontaneous firing rate, which was prevented by the NO-scavenger, carboxy
      PTIO (300 microM). The SNP effects were not modified (+37.4%) by synaptic
      uncoupling, suggesting that NO influences intrinsic membrane properties of MVNn
      rather than the synaptic input they receive. The excitatory action of SNP was
      virtually abolished by slice pretreatment with the soluble guanylyl cyclase
      inhibitor, ODQ (10 microM), and it was mimicked (+33.1%) by the cGMP analogue 8
      Br-cGMP (400 microM). Protein kinase G (PKG) and cAMP/protein kinase A (PKA) were
      both excluded as downstream effectors of the NO/cGMP-induced excitation. However,
      the cyclic nucleotide-gated (CNG) channel blockers, L-cis-diltiazem (LCD, 100
      microM) and Sp-8-Br-PET-cGMPS (100 microM), significantly reduced the firing rate
      increase produced by 8-Br-cGMP. Moreover, LCD alone decreased spontaneous MVNn
      firing (-19.7%), suggesting that putative CNG channels may contribute to the
      tonic control of resting MVNn discharge. 8-Br-cAMP (1 mM) also elicited
      excitatory effects in MVNn (+40.8%), which occluded those induced by 8-Br-cGMP,
      indicating that the two nucleotides share a common target. Finally, nested
      polymerase chain reaction assay revealed the expression of CNG channel alpha
      subunit transcript in MVNn. Our data provide the first demonstration that NO/cGMP
      signalling modulates MVNn spontaneous firing through a mechanism that is
      independent of PKG or PKA and probably involves activation of CNG channels.

PMID- 15450092
TI  - Unilateral cochlear ablation produces greater loss of inhibition in the
      contralateral inferior colliculus.
AB  - Bilateral cochlear ablation leads to a profound weakening of synaptic inhibition
      within the inferior colliculus (IC) of gerbils [Vale & Sanes (2000) J. Neurosci.,
      20, 1912-1921]. To examine whether unilateral deafening leads to similar
      functional alterations, we studied the effect of unilateral cochlear ablation on
      inhibitory synaptic properties both ipsilateral and contralateral to the deafened
      ear. Lateral lemniscal and commissure of the IC-evoked inhibitory postsynaptic
      currents (IPSCs) were recorded in an IC brain slice preparation using whole-cell
      and gramicidin perforated-patch electrodes in the presence of kynurenic acid.
      Unilateral cochlear ablation led to a 23 mV depolarizing shift in the IPSC
      equilibrium potential for IC neurons contralateral to the deafened ear, but only
      a 10 mV depolarization in the ipsilateral IC. Lateral lemniscal-evoked inhibitory
      synaptic conductance declined significantly in the ipsilateral and contralateral
      IC, whereas commissural-evoked inhibitory synaptic conductance declined only
      contralateral to the ablated cochlea. An analysis of paired-pulse facilitation
      showed that inhibitory transmitter release was more affected ipsilateral to the
      ablated cochlea. Thus, unilateral cochlear ablation modifies inhibitory synapses
      in the inferior colliculus, but these changes appear to be dominated by
      postsynaptic alterations in the contralateral IC, and by presynaptic changes in
      the ipsilateral IC.

PMID- 15450093
TI  - Multiple GABAA receptor subtypes regulate hippocampal ripple oscillations.
AB  - High-frequency oscillations (140-200 Hz) were recorded in behaving rats from the
      CA1 area of the hippocampus. As generation of these synchronous patterns is
      assumed to depend on coordinated interneuronal inhibition, we studied the
      interference of benzodiazepines with the fine structure and occurrence of ripple
      oscillations. The nonselective GABAA receptor alpha-subunit agonist, diazepam,
      lowered the frequency of ripple oscillations and reduced their occurrence,
      amplitude and duration. Zolpidem, an alpha1-subunit selective benzodiazepine
      elevated ripple duration but acted similar to diazepam in other respects. The
      nonselective alpha-subunit benzodiazepine antagonist, flumazenil, reduced ripple
      numbers, amplitude and duration. Wavelet based analysis of the dynamics of
      intraripple frequency revealed a dramatic decay within a ripple. Only diazepam (1
      mg/kg) accelerated this intraripple frequency accommodation. The effects were not
      due to increased behavioural activity and alertness as evident from vigilance
      state control. The results suggest a differential role of GABAA receptor subtype
      specific inhibitory mechanisms in the mediation and fine-tuning of the network
      synchronization during approximately 200 Hz hippocampal oscillations.

PMID- 15450094
TI  - In vivo contribution of h-channels in the septal pacemaker to theta rhythm
      generation.
AB  - One of the most intriguing network-level inferences made on the basis of in vitro
      and modelling data regarding the role of Ih current was that they participate in
      rhythmogenesis in different parts of the brain. The nature of Ih contribution to
      various neuronal oscillations is far from uniform however, and the proper
      evaluation of the role of Ih in each particular structure requires in situ
      investigations in the intact brain. In this study we tested the effect of Ih
      blockade in the medial septum on hippocampal theta rhythm in anaesthetized and
      freely behaving rats. We could not confirm the recent report of elimination of
      theta by septal injection of ZD7288 [C. Xu et al. (2004) Eur. J. Neurosci., 19,
      2299-2309]; the observed effects were more subtle and more specific. We found
      that Ih blockade in the medial septum substantially decreased the frequency of
      hippocampal oscillations without changing the context in which theta occurred,
      i.e. specific behaviours in freely moving rats and spontaneous switching and
      brainstem stimulation under anaesthesia. Septal injection of ZD7288 eliminated
      atropine-resistant theta elicited by high intensity electrical stimulation of the
      reticular formation in anaesthetized rats but was ineffective in combination with
      the muscarinic agonist, carbachol. Thus, functional Ih was necessary for the
      septum to generate or transmit high frequency theta rhythm elicited by strong
      ascending activation, whereas low frequency theta persisted after Ih blockade.
      These results suggest that Ih plays a specific role in septal theta generation by
      promoting fast oscillations during exploratory behaviour and rapid eye movement
      sleep.

PMID- 15450095
TI  - Locomotor and oculomotor impairment associated with cerebellar dysgenesis in Zic3
      deficient (Bent tail) mutant mice.
AB  - We examined the adult neural phenotypes of the Bent tail mutant mouse. The Bent
      tail mutant mouse was recently shown to lack a submicroscopic part of the X
      chromosome containing the Zic3 gene, which encodes a zinc-finger protein
      controlling vertebrate neural development. While nearly one-fourth of hemizygous
      Bent tail (Bn/Y, Zic3-deficient) mice developed neural tube defects in their
      midbrain and hindbrain region, the other Bn/Y mice showed apparently normal
      behaviour in a C57BL/6 genetic background. A battery of behavioural and eye
      movement tests revealed impaired spontaneous locomotor activity, reduction of
      muscle tone and impairments of vestibuloocular and optokinetic eye movements in
      these mice. Morphological examination of the mutant brain showed a significant
      reduction in the cell numbers in the cerebellar anterior lobe and paraflocculus
      flocculus complex. Our results indicate that the cerebellar dysgenesis
      characterized by subregional hypoplasia affects the locomotor activity, muscle
      tone and eye movement control of the mice. These findings may have some clinical
      implications in relation to disorders characterized by cerebellar dysgenesis,
      such as Joubert syndrome.

PMID- 15450096
TI  - Behavioural correlates of an altered balance between synaptic and extrasynaptic
      GABAAergic inhibition in a mouse model.
AB  - GABAA receptors mediate fast phasic inhibitory postsynaptic potentials and
      participate in slower tonic extrasynaptic inhibition. Thy1alpha6 mice with
      ectopic forebrain expression of GABAA receptor alpha6 subunits exhibit increased
      extrasynaptic GABAA receptor-mediated background conductance and reduced synaptic
      GABAA receptor currents in hippocampal CA1 neurons [W. Wisden et al. (2002)
      Neuropharmacology 43, 530-549]. Here we demonstrate that isolated CA1 neurons of
      these mice showed furosemide-sensitivity of GABA-evoked currents, confirming the
      functional expression of alpha6 subunit. In addition, receptor autoradiography of
      the CA1 region of Thy1alpha6 brain sections revealed pharmacological features
      that are unique for alpha6betagamma2 and alpha6beta receptors. The existence of
      atypical alpha6beta receptors was confirmed after completely eliminating GABAA
      receptors containing gamma1, gamma2, gamma3 or delta subunits using serial
      immunoaffinity chromatography on subunit-specific GABAA receptor antibodies.
      Behaviourally, the Thy1alpha6 mice showed normal features with slightly enhanced
      startle reflex and struggle-escape behaviours. However, they were more sensitive
      to GABAA antagonists DMCM (shorter latency to writhing clonus) and picrotoxinin
      (shorter latency to generalized convulsions). Tiagabine, an antiepileptic GABA
      uptake inhibitor that increases brain GABA levels, delayed picrotoxinin-induced
      convulsions at a low dose of 3.2 mg/kg in Thy1alpha6 mice, but not in control
      mice; however, the overall effect of higher tiagabine doses on the convulsion
      latency remained smaller in the Thy1alpha6 mice. Altered balance between
      extrasynaptic and synaptic receptors thus affects seizure sensitivity to
      GABAergic convulsants. Importantly, the increased extrasynaptic inhibition, even
      when facilitated in the presence of tiagabine, was not able fully to counteract
      enhanced seizure induction by GABAA antagonists.

PMID- 15450097
TI  - GABAA receptors signal bidirectional reward transmission from the ventral
      tegmental area to the tegmental pedunculopontine nucleus as a function of opiate
      state.
AB  - The brainstem tegmental pedunculopontine nucleus (TPP) is involved in reward
      signalling and is functionally and anatomically linked to the VTA. We examined
      the possible role of the TPP as a reward transmission output for GABAA receptors
      in the VTA in rats not previously exposed to opiates vs. rats that were
      chronically exposed to and in withdrawal from opiates or in rats that had
      recovered from chronic opiate exposure. Bilateral lesions of the TPP blocked the
      rewarding effects of a GABAA antagonist but not the rewarding effects of a GABAA
      receptor agonist in rats previously unexposed to opiates. This functional pattern
      was reversed in rats that were dependent on opiates and in withdrawal. However,
      once rats had recovered from chronic opiate exposure the functional parameters of
      VTA GABAA receptor reward signalling reverted to the pattern observed in animals
      that had not been exposed to opiates. These findings suggest that GABAA receptors
      in the VTA can regulate differential reward signalling through separate neural
      systems during the transition from a drug-naive to a drug-dependent and withdrawn
      state.

PMID- 15450098
TI  - The role of the magnocellular pathway in serial deployment of visual attention.
AB  - Normal human visual function often demands detection of a target among a number
      of other objects cluttering the scene, such as when searching for a known face in
      a crowd. In these and similar tasks, the search performed is a serial one, with
      an attentional spotlight scanning the objects of the scene. We have investigated
      whether one of the afferent channels in vision, the colour-blind magnocellular
      pathway, is essential in such serial searches. We did this by using items that
      were isoluminant with the background but of a different colour, for which the
      magnocellular cells would be blind. The search in these conditions required much
      longer reaction times than when even a very small luminance contrast (2%) was
      added to the items. Because such luminance contrasts can be detected only by
      magnocellular cells and not by neurons of the other channels (parvocellular and
      koniocellular), the magnocellular pathway appears vitally important for serial
      search. In contrast, in a feature search task, which does not require allocation
      of attentional resources, the search was as efficient with isoluminance as when
      luminance contrast was added to the items.

PMID- 15450099
TI  - Modulation of premotor mirror neuron activity during observation of unpredictable
      grasping movements.
AB  - Using transcranial magnetic stimulation, we explored the properties of premotor
      mirror neurons during the passive observation of a reaching-grasping movement in
      human subjects. Two different experiments were run using video-clips as visual
      stimuli. Video-clips showed a normally performed (control stimulus) or an
      anomalous reaching-grasping movement executed by delaying the time of the
      appearance of the maximal finger aperture (experiment 1), or substituting it with
      an unpredictable closure (experiment 2). Motor evoked potentials were recorded at
      different time-points during the observation of the video-clips. Profiles of
      cortical excitability were drawn and compared with the kinematic profiles of the
      corresponding movement. Passive observation of the natural movement evoked a
      profile of cortical excitability that is in concordance with the timing of the
      kinematic profile of the shown finger movements. Observation of the uncommon
      movements did not exert any modulation (experiment 1) or evoked an activity that
      matched, at the beginning, the modulation obtained with observation of the
      natural movement (experiment 2). Results show that the resonant motor plan is
      loaded as whole at the beginning of observation and once started tends to proceed
      to its completion regardless of changes to the visual cues. The results exclude
      the possibility of a temporal fragmentation of the resonant plan, because
      activation of different populations of mirror neurons for each phase of the
      ongoing action. They further support the notion of the role of the mirror system
      as neural substrate for the observing-execution matching system and extend the
      current knowledge regarding mechanisms that trigger the internal representation
      of an action.

PMID- 15450100
TI  - Adenosine A2A receptors are involved in physical dependence and place
      conditioning induced by THC.
AB  - A2A adenosine and CB1 cannabinoid receptors are highly expressed in the central
      nervous system, where they modulate numerous physiological processes including
      adaptive responses to drugs of abuse. Both purinergic and cannabinoid systems
      interact with dopamine neurotransmission (through A2A and CB1 receptors,
      respectively). Changes in dopamine neurotransmission play an important role in
      addictive-related behaviours. In this study, we investigated the contribution of
      A2A adenosine receptors in several behavioural responses of Delta9
      tetrahydrocannabinol (THC) related to its addictive properties, including
      tolerance, physical dependence and motivational effects. For this purpose, we
      first investigated acute THC responses in mice lacking A2A adenosine receptors.
      Antinociception, hypolocomotion and hypothermia induced by acute THC
      administration remained unaffected in mutant mice. Chronic THC treatment
      developed similar tolerance to these acute effects in wild-type and A2A-knockout
      mice. However, differences in the body weight pattern were found between
      genotypes during such chronic treatment. Interestingly, the somatic
      manifestations of SR141716A-precipitated THC withdrawal were significantly
      attenuated in mutant mice. The motivational responses of THC were also evaluated
      by using the place-conditioning paradigm. A significant reduction of THC-induced
      rewarding and aversive effects was found in mice lacking A2A adenosine receptors
      in comparison with wild-type littermates. Binding studies revealed that these
      behavioural changes were not associated with any modification in the distribution
      and/or functional activity of CB1 receptors in knockout mice. Therefore, this
      study shows, for the first time, a specific involvement of A2A receptors in the
      addictive-related properties of cannabinoids.

PMID- 15450101
TI  - Benzodiazepine impairment of perirhinal cortical plasticity and recognition
      memory.
AB  - Benzodiazepines, including lorazepam, are widely used in human medicine as
      anxiolytics or sedatives, and at higher doses can produce amnesia. Here we
      demonstrate that in rats lorazepam impairs both recognition memory and synaptic
      plastic processes (long-term depression and long-term potentiation). Both
      impairments are produced by actions in perirhinal cortex. The findings thus
      establish a mechanism by means of which benzodiazepines impair recognition
      memory. The findings also strengthen the hypotheses that the familiarity
      discrimination component of recognition memory is dependent on reductions in
      perirhinal neuronal responses when stimuli are repeated and that these response
      reductions are due to a plastic mechanism also used in long-term depression.

PMID- 15450102
TI  - Bimodal speech: early suppressive visual effects in human auditory cortex.
AB  - While everyone has experienced that seeing lip movements may improve speech
      perception, little is known about the neural mechanisms by which audiovisual
      speech information is combined. Event-related potentials (ERPs) were recorded
      while subjects performed an auditory recognition task among four different
      natural syllables randomly presented in the auditory (A), visual (V) or congruent
      bimodal (AV) condition. We found that: (i) bimodal syllables were identified more
      rapidly than auditory alone stimuli; (ii) this behavioural facilitation was
      associated with cross-modal [AV-(A+V)] ERP effects around 120-190 ms latency,
      expressed mainly as a decrease of unimodal N1 generator activities in the
      auditory cortex. This finding provides evidence for suppressive, speech-specific
      audiovisual integration mechanisms, which are likely to be related to the
      dominance of the auditory modality for speech perception. Furthermore, the
      latency of the effect indicates that integration operates at pre-representational
      stages of stimulus analysis, probably via feedback projections from visual and/or
      polymodal areas.

PMID- 15450103
TI  - Astroglial processes show spontaneous motility at active synaptic terminals in
      situ.
AB  - Within the tripartite structure of vertebrate synapses, enwrapping astroglial
      processes regulate synaptic transmission by transmitter uptake and by direct
      transmitter release. We applied confocal and two-photon laser scanning microscopy
      to acutely isolated slices prepared from the brainstem of transgenic TgN(GFAP
      EGFP) mice. In transversal sections fluorescently labelled astrocytes are evenly
      distributed throughout the tissue. Astroglial processes contacted neuronal somata
      and enwrapped active synaptic terminals as visualized using FM1-43 staining in
      situ. Here, at these synaptic regions astroglial process endings displayed a high
      degree of dynamic morphological changes. Two defined modes of spontaneous
      motility could be distinguished: (i) gliding of thin lamellipodia-like membrane
      protrusions along neuronal surfaces and (ii) transient extensions of filopodia
      like processes into the neuronal environment. Our observations highlight the
      active role of astrocytes in direct modulation of synaptic transmission.

PMID- 15450104
TI  - Single-pulse transcranial magnetic stimulation over the frontal eye field can
      facilitate and inhibit saccade triggering.
AB  - The aim of this study was to investigate the effect of single-pulse transcranial
      magnetic stimulation on the triggering of saccades. The right frontal eye field
      was stimulated during modified gap and overlap paradigms with flashed
      presentation of the lateral visual target of 80 ms. In order to examine possible
      facilitating or inhibitory effects on saccade triggering, three different time
      intervals of stimulation were chosen, i.e. simultaneously with onset of the
      target, during the presentation and after target end. Stimulation applied
      simultaneously with target onset significantly decreased the latency of
      contralateral saccades in the gap but not in the overlap paradigm. Stimulation
      after target end significantly increased saccade latency for both sides in the
      gap paradigm and for the contralateral side in the overlap paradigm. Stimulation
      during presentation had no effect in either paradigm. The results show that,
      depending on the time interval and the paradigm tested, a facilitation or
      inhibition of saccade triggering can be achieved. The results are discussed in a
      context of two probable transcranial magnetic stimulation effects, a direct
      interference with the frontal eye field on the one hand and a remote interference
      with the superior colliculus on the other hand.

PMID- 15450105
TI  - Transcranial magnetic stimulation of the human motor cortex influences the
      neuronal activity of subthalamic nucleus.
AB  - The critical role of the subthalamic nucleus (STN) in the control of movement and
      parkinsonian symptoms is well established. Research in animals suggests that the
      cerebral cortex plays an important role in regulating the activity of the STN but
      this control is not known in humans. The most extensive cortical innervation of
      the STN originates from motor areas. Here, we used transcranial magnetic
      stimulation (TMS) during intraoperative single-unit recordings from STN, in six
      patients with Parkinson's disease (PD) undergoing implantation of deep brain
      stimulators, to determine whether TMS of the motor cortex (MC) modulates the
      activity of STN and to investigate in vivo the functional organization of the
      corticosubthalamic circuit in the human brain. Single-pulse TMS of the MC induced
      an excitation in 74.9% of neurons investigated. This activation was followed by a
      long-lasting inhibition of the STN neuronal activity that did not correlate with
      PD severity. Responsive neurons to TMS of the hand area of motor cortex were
      located mainly in the lateral and dorsal region of the subthalamus while
      unresponsive cells had a prevalently medial distribution. This is the first
      report of TMS-induced modulation of STN neuronal activity in humans. These
      findings open up new avenues for in vivo studies of corticosubthalamic
      interactions in human brain and PD.

PMID- 15450107
TI  - Pressure-independent cardiac effects of angiotensin II in pigs.
AB  - BACKGROUND: Angiotensin II (Ang II) is a potent vasoconstrictor with an important
      role in the development of cardiovascular disease. Earlier results have shown a
      positive acute inotropic effect of Ang II in anaesthetized pigs together with
      significant vasoconstriction. This investigation was designed to study cardiac
      effects of Ang II, when blood pressure was maintained constant by experimental
      means. METHODS: Ang II (200 microg h(-1)) was infused in anaesthetized pigs (n =
      10) at two different arterial blood pressures, the first determined by the
      effects of Ang II alone, and the second maintained at baseline blood pressure
      with nitroprusside. Cardiac systolic and diastolic function was evaluated by
      analysis of left ventricular pressure-volume relationships. RESULTS: Heart rate,
      end-systolic elastance (Ees) and pre-load adjusted maximal power (PWRmax EDV(-2))
      increased at both blood pressure levels, although less when blood pressure was
      kept constant with nitroprusside. The time constant for isovolumetric relaxation
      (tau(1/2)) was prolonged with Ang II alone and shortened with Ang II infused
      together with nitroprusside. CONCLUSION: Ang II infusion in the pig has inotropic
      and chronotropic properties independent of arterial blood pressure levels,
      although the effects seem to be blunted by pharmacological actions of the nitric
      oxide donor nitroprusside.

PMID- 15450108
TI  - Participation of Na/Ca-exchanger and sarcoplasmic reticulum in the high [K]
      protection against ischaemia-reperfusion dysfunction in rat hearts.
AB  - AIM: Na/Ca-exchanger (NCX) and sarcoplasmic reticulum (SR) roles during the
      protection by a cardioplegic solution (25 mm K and 0.5 mm Ca, CPG) against
      ischaemia-reperfusion was studied. METHODS: Contractile performance (CP) and high
      energy phosphates contents (HEP) were evaluated in isolated ventricles from rats.
      They were pre-treated with Krebs (C) or CPG and submitted to no-flow ischaemia
      and reperfusion (I-R). KB-R7943 5 microm (inhibitor of NCX in reverse mode), 8 mm
      caffeine and ionic changes were used pre-ischaemically to evaluate each pathway
      role. RESULTS: During R, CP recovered to 77 +/- 8% of basal in CPG-hearts vs. 55
      +/- 8% (P < 0.05) in C-ones. CPG avoided the increases in end diastolic pressure
      (LVEDP) and in PCr/ATP ratio during I-R. Low [Na]o (78 mm) under both, CPG-2 mm
      Ca and C, increased further the LVEDP during I-R. LVEDP was also transiently
      increased by caffeine-CPG, but not modified by KB-R7943. The recovery of CP
      during reperfusion of CPG-hearts was decreased either, by caffeine (to
      approximately 75%), low [Na]o-2 mm Ca-CPG (to approximately 40%) and KB-R7943 (to
      approximately 16%). CONCLUSIONS: CPG protected hearts from ischaemic contracture
      by attenuating the fall in ATP and removing diastolic Ca by means of NCX in
      forward mode. Moreover, CPG induces higher CP recovery during reperfusion by
      participation of SR and NCX in reverse mode. This work remarks the use of CPG
      based on the functional role of these Ca handling-mechanisms in a
      pathophysiological condition as ischaemia-reperfusion.

PMID- 15450109
TI  - Adenosine A receptors are necessary for protection of the murine heart by remote,
      delayed adaptation to ischaemia.
AB  - AIMS: Adenosine is involved in classic pre-conditioning (PC) in most species,
      acting through especially adenosine A1 and A3 receptors. We studied whether the
      adenosine A1 receptor (A1R) was important for remote, delayed adaptation to
      ischaemia using a mouse with targeted deletion of the A1R gene. METHODS: Remote,
      delayed adaptation was evoked by brain ischaemia (BIPC) through bilateral
      ligation of the internal carotid arteries. Through microdialysis probes placed in
      the brain and the abdominal aorta, we found that plasma adenosine increased
      following carotid artery ligation. Twenty-four hours after ligation, hearts were
      isolated, Langendorff perfused and subjected to 40 min global ischaemia and 60
      min reperfusion. Hearts from sham operated and BIPC animals either with (A1R+/+)
      or without (A1R-/-) the gene for the adenosine A(1)R were compared with each
      other. RESULTS: In wild types, BIPC reduced infarct size and improved functional
      recovery during reperfusion, but BIPC did not protect hearts of A1R-/- mice.
      There were no significant differences between sham-operated A1R+/+ and A1R-/- in
      recovery of function or infarct size. The mitogen-activated protein kinases
      (MAPKs) extracellular signal-regulated protein kinase1/2 (ERK1/2), p38 and c-jun
      N-terminal kinase (JNK) were phosphorylated during reperfusion of sham treated
      hearts. The increase in ERK1/2 and p38 phosphorylation detected was attenuated in
      hearts of BIPC or A1R-/- animals. CONCLUSION: During BIPC adenosine acting on the
      A1R appears necessary for myocardial protection. MAPK signalling may possibly be
      involved in organ protection during the delayed phase of remote, delayed
      adaptation.

PMID- 15450110
TI  - The stimulatory effect of alpha-melanotropin on progesterone release from rat
      granulosa cells is inhibited by interleukin-1beta and by tumour necrosis factor
      alpha.
AB  - AIM: Several studies have shown that a variety of peptides and cytokines are
      involved in ovarian regulatory mechanisms; however, their exact function is still
      unclear. In this work we study whether the administration of peptide alpha
      melanotropin and the cytokines interleukin-1beta (IL-1beta) and tumour necrosis
      factor-alpha (TNF-alpha) on their own modify the release of progesterone in
      cultured granulosa cells (GC) from pro-oestrous rats. We also investigate an
      interaction between these cytokines and alpha-melanotropin in the modulation of
      progesterone secretion. METHODS: Granulosa cells were collected from the ovaries
      of female Wistar rats and cultured for up to 24 h in the presence of different
      concentrations of alpha-melanotropin, cytokines or a combination of both.
      Progesterone concentration was measured by radioimmunoassay. RESULTS: The
      addition of alpha-melanotropin in a dose of 0.01 and 0.1 mm had no effect on
      progesterone release, whereas a dose of 1 mm significantly increased progesterone
      release (P < 0.01) compared with the control culture. Progesterone release was
      not modified when different concentrations of interleukin-1beta or TNF-alpha were
      added to the cell cultures. However, when interleukin-1beta or TNF-alpha were
      added simultaneously with 1 microm alpha-melanotropin, a significant reduction (P
      < 0.01 for interleukin-1beta and P < 0.05 for TNF-alpha) of the steroid release
      was found with respect to the alpha-melanotropin-treated group. CONCLUSIONS:
      These results lead us to suggest that, although alpha-melanotropin stimulates
      progesterone release in pre-ovulatory GC, this effect is blocked by the presence
      of interleukin-1beta or TNF-alpha.

PMID- 15450111
TI  - Effects of acute moderate exercise on the phagocytosis of Kupffer cells in rats.
AB  - AIM: This study investigated the function of Kupffer cells, and particularly
      their role as immunocompetent cells that come into contact with gut-derived
      endotoxin, in the acute exercise of rats. METHODS: Female Fischer 344 rats were
      run on a treadmill at 21 m min(-1) for 60 min on a 15% grade. RESULTS:
      Afterwards, the number of latex particles in the liver was higher in the
      exercising rats than that in resting rats and an increase in the number of latex
      particles phagocytosed by each Kupffer cell was noted. The plasma endotoxin
      concentration was significantly higher in the exercise group than in the resting
      rats, and the small intestine was damaged by the exercise. Plasma corticosterone
      and thyroxine 4 levels were unchanged. Although the number of Kupffer cells was
      unchanged by acute exercise, the number of CD14-positive Kupffer cells increased.
      Plasma liver enzyme activities were slightly increased by acute exercise, whereas
      plasma tumour necrosis factor-alpha was not detected. CONCLUSION: These results
      suggest that moderately intense exercise increases the phagocytosis of Kupffer
      cells, and that it might be induced by endotoxemia of portal blood caused by
      intestinal mucosal lesions resulting from acute exercise.

PMID- 15450112
TI  - Exercise and myocardial tolerance to ischaemia-reperfusion.
AB  - It is well established that both short-term (1-5 days) and long-term (weeks to
      months) high intensity exercise (i.e. 70-75%VO2max) provides cardioprotection
      against ischaemia-reperfusion injury. However, it is unclear if moderate
      intensity exercise will also provide cardioprotection. AIM: Therefore, these
      experiments compared the protective effects of moderate vs. high intensity
      exercise in providing defense against ischaemia-reperfusion injury. METHODS: Male
      Sprague-Dawley rats were randomly assigned to one of three-experimental groups:
      (1) sedentary (control); (2) moderate intensity treadmill exercise (60 min day(
      1) at approximately 55%VO2max); or (3) high intensity treadmill exercise (60 min
      day(-1) at approximately 75%VO2max). Hearts were exposed to 20 min of global
      ischaemia followed by 30 min reperfusion in an isolated working heart
      preparation. RESULTS: Compared with sedentary rats, both moderate and high
      intensity exercised rats maintained a higher (P < 0.05) percentage of pre
      ischaemia cardiac output and cardiac work (cardiac output x systolic blood
      pressure) during reperfusion. No differences in the percent recovery of cardiac
      output and heart work existed (P > 0.05) between the two exercise groups.
      CONCLUSIONS: These data reveal that both moderate and high intensity exercise
      training provide equivalent protection against ischaemia-reperfusion injury.

PMID- 15450113
TI  - Evaluation of a triple sugar test of colonic permeability in humans.
AB  - AIM: Conventional dual sugar tests of intestinal permeability assess only the
      stomach and small intestine. A novel triple sugar method of assessing colonic
      permeability has recently been described in animals. This utilizes the non
      fermented sweetener sucralose, in addition to conventional sugars. It has been
      postulated that this test enables the simultaneous assessment of small-intestinal
      and colonic barrier function in humans. The aim of this study was to evaluate the
      triple sugar test using healthy volunteers and ileostomists. METHODS: Twenty-one
      healthy volunteers and 18 ileostomists underwent the triple sugar test. After an
      overnight fast, subjects drank a solution containing lactulose (5 g), rhamnose (1
      g) and sucralose (5 g). Urine was collected for 0-5 h and 5-19 h. Urinary sugars
      were quantified using HPLC, and 5 and 24-h excretion calculated. Nineteen control
      subjects and 16 ileostomists also underwent a 51Cr-EDTA permeability test.
      Permeability data were presented as medians (IQR), and differences between groups
      analysed with Mann-Whitney U-tests. RESULTS: Lactulose excretion and the 5-h
      lactulose/rhamnose (L/R) ratio were similar in controls and ileostomists [L/R
      ratio 0.024 (0.022-0.034) vs. 0.025 (0.022-0.035), P = 0.955]. Twenty-four hours
      excretion of sucralose was significantly higher in control subjects compared with
      ileostomists [1.41% (1.17-1.68) vs. 0.96% (0.64-1.2), P = 0.003]. The same
      pattern was seen with 51Cr-EDTA [2.73% (2.06-3.76) vs. 2.06% (1.55-2.71), P =
      0.037] and with lactulose [0.52% (0.42-0.60) vs. 0.25% (0.16-0.35), P = 0.002].
      CONCLUSIONS: Both sucralose and 51Cr-EDTA underwent significant colonic
      absorption. A significant amount of lactulose also appeared to be absorbed in the
      colon. This unexpected finding requires further study.

PMID- 15450114
TI  - Metabolic cost of lengthening, isometric and shortening contractions in maximally
      stimulated rat skeletal muscle.
AB  - AIM: The present study investigated the energy cost of lengthening, isometric and
      shortening contractions in rat muscle (n = 19). METHODS: With electrical
      stimulation the rat medial gastrocnemius muscle was maximally stimulated to
      perform 10 lengthening, isometric and shortening contractions (velocity 25 mm s(
      1)) under experimental conditions (e.g. temperature, movement velocity) that
      resemble conditions in human movement. RESULTS: Mean +/- SD force-time-integral
      of the first contraction was significantly different between the three protocols,
      2.4 +/- 0.2, 1.7 +/- 0.2 and 1.0 +/- 0.2 N s, respectively (P < 0.05). High
      energy phosphate consumption was not significantly different between the three
      modes of exercise but a trend could be observed from lengthening (7.7 +/- 2.7
      micromol approximately P muscle(-1)) to isometric (8.9 +/- 2.2 micromol
      approximately P muscle(-1)) to shortening contractions (10.4 +/- 1.6 micromol
      approximately P muscle(-1)). The ratio of high-energy phosphate consumption to
      force-time-integral was significantly lower for lengthening [0.3 +/- 0.1 micromol
      approximately P (N s)(-1)] and isometric [0.6 +/- 0.2 micromol approximately P (N
      s)(-1)] contractions compared with shortening [1.2 +/- 0.2 micromol approximately
      P (N s)(-1)] contractions (P < 0.05). CONCLUSION: The present results of
      maximally stimulated muscles are comparable with data in the literature for
      voluntary human exercise showing that the energy cost of force production during
      lengthening exercise is approximately 30% of that in shortening exercise. The
      present study suggests that this finding in humans probably does reflect
      intrinsic muscle properties rather than effects of differential recruitment
      and/or coactivation.

PMID- 15450115
TI  - Human soleus muscle protein synthesis following resistance exercise.
AB  - AIM: It is generally believed the calf muscles in humans are relatively
      unresponsive to resistance training when compared with other muscles of the body.
      The purpose of this investigation was to determine the muscle protein synthesis
      response of the soleus muscle following a standard high intensity bout of
      resistance exercise. METHODS: Eight recreationally active males (27 +/- 4 years)
      completed three unilateral calf muscle exercises: standing calf press/heel raise,
      bent-knee calf press/heel raise, and seated calf press/heel raise. Each exercise
      consisted of four sets of 15 repetitions (approximately 15 repetition maximum,
      RM, or approximately 70% 1RM). Fractional rate of muscle protein synthesis (FSR)
      was determined with a primed constant infusion of [2H5]phenylalanine coupled with
      muscle biopsies immediately and 3 h following the exercise in both the exercise
      and non-exercise (resting control) leg. RESULTS: FSR was elevated (P < 0.05) in
      the exercise (0.069 +/- 0.010) vs. the control (0.051 +/- 0.012) leg. Muscle
      glycogen concentration was lower (P < 0.05) in the exercise compared with the
      control leg (Decrease from control; immediate post-exercise: 54 +/- 5; 3 h post
      exercise: 36 +/- 4 mmol kg(-1) wet wt.). This relatively high amount of glycogen
      use is comparable with previous studies of resistance exercise of the thigh (i.e.
      vastus lateralis; approximately 41-49 mmol kg(-1) wet wt.). However, the exercise
      induced increase in FSR that has been consistently reported for the vastus
      lateralis (approximately 0.045-0.060% h(-1)) is on average approximately 200%
      higher than reported here for the soleus (0.019 +/- 0.003% h(-1)). CONCLUSIONS:
      These results suggest the relatively poor response of soleus muscle protein
      synthesis to an acute bout of resistance exercise may be the basis for the
      relative inability of the calf muscles to respond to resistance training
      programs.

PMID- 15450116
TI  - The effect of AVP-V receptor stimulation on local GFR in the rat kidney.
AB  - AIM: Arginine vasopressin (AVP) might influence urinary concentration ability by
      altering the intrarenal distribution of glomerular filtration rate (GFR).
      METHODS: To study this possibility we have measured the intracortical
      distribution of GFR following acute AVP-V1 receptor stimulation in anaesthetized
      female Sprague-Dawley (SPD) rats during euvolemia and water diuresis by the
      aprotinin method, allowing two consecutive measurements of zonal GFR in the same
      kidney. RESULTS: Acute i.v. bolus injection of 50 ng V1 receptor agonist ([Phe2,
      Ile3, Orn8]-vasopressin) followed by a continuous infusion of 5 ng min(-1) in
      euvolemic rats reduced GFR by 25% in outer cortex (OC), 20% in middle cortex (MC)
      and 19% in inner cortex (IC) relative to vehicle infusion (all P < 0.05). In
      water diuretic rats V1 receptor agonist reduced GFR by 22% in OC, 10% in MC and
      11% in IC relative to vehicle infusion (P < 0.05). GFR decreased slightly more in
      OC than in MC and IC in both euvolemic and water diuretic rats (P < 0.05)
      indicating a distribution of GFR towards MC and IC. Acute infusion of the
      selective non-peptide V1 receptor antagonist OPC-21268 in euvolemic rats reduced
      GFR by 14% in OC, 13% in MC and 11% in IC relative to vehicle infusion (P <
      0.05), with no significant difference between the layers. CONCLUSIONS: The change
      in distribution of GFR not only between OC and IC, but also between OC and MC
      suggests that the afferent/efferent arterioles and not the medullary vasa recta
      is the main site of resistance change. We conclude that acute i.v. infusion of V1
      receptor agonist in high doses reduces GFR more in superficial than in deep
      cortex in both euvolemic and water diuretic rats and that this may be of some
      importance for water conservation, adding to the V2- receptor effect on water
      permeability of the collecting ducts.

PMID- 15450117
TI  - Control of breathing in newborn mice lacking the beta-2 nAChR subunit.
AB  - AIM: To study the ventilatory and arousal/defence responses to hypoxia in newborn
      mutant mice lacking the beta2 subunit of the nicotinic acetylcholine receptors.
      METHODS: Breathing variables were measured non-invasively in mutant (n = 31) and
      wild-type age-matched mice (n = 57) at 2 and 8 days of age using flow barometric
      whole-body plethysmography. The arousal/defence response to hypoxia was
      determined using behavioural criteria. RESULTS: On day 2, mutant pups had
      significantly greater baseline ventilation (16%) than wild-type pups (P < 0.02).
      Mutant pups had a decreased hypoxic ventilatory declines. Arousal latency was
      significantly shorter in mutant than in wild-type pups (133 +/- 40 vs. 146 +/- 20
      s, respectively, P < 0.026). However, the duration of movement elicited by
      hypoxia was shorter in mutant than in wild-type pups (14.7 +/- 5.9 vs. 23.0 +/-
      10.7 s, respectively, P < 0.0005). Most differences disappeared on P8, suggesting
      a high degree of functional plasticity. CONCLUSION: The blunted hypoxic
      ventilatory decline and the shorter arousal latency on day 2 suggested that
      disruption of the beta2 nicotinic acetylcholine receptors impaired inhibitory
      processes affecting both the ventilatory and the arousal response to hypoxia
      during postnatal development.

PMID- 15450118
TI  - Exposure to malaria affects the regression of hepatosplenomegaly after treatment
      for Schistosoma mansoni infection in Kenyan children.
AB  - BACKGROUND: Schistosoma mansoni and malaria infections are often endemic in the
      same communities in sub-Saharan Africa, and both have pathological effects on the
      liver and the spleen. Hepatosplenomegaly associated with S. mansoni is
      exacerbated in children with relatively high exposure to malaria. Treatment with
      praziquantel reduces the degree of hepatosplenomegaly, but the condition does not
      completely resolve in some cases. The present analysis focused on the possibility
      that exposure to malaria infection may have limited the resolution of
      hepatosplenomegaly in a cohort of Kenyan schoolchildren. METHODS: Ninety-six
      children aged 6-16, from one community in Makueni district, Kenya, were treated
      with praziquantel. At baseline, all children had hepatomegaly and most had
      splenomegaly. The source of S. mansoni infection, a river, was molluscicided
      regularly over the following three years to limit S. mansoni re-infection,
      whereas malaria exposure was uninterrupted. Hepatic and splenic enlargement was
      assessed annually outside the malaria transmission season. RESULTS: Children
      living in an area of relatively high exposure to both infections presented with
      the largest spleens before treatment and at each follow-up. Spleens of firm
      consistency were associated with proximity to the river. The regression of
      hepatomegaly was also affected by location, being minimal in an area with
      relatively low S. mansoni exposure but high exposure to malaria, and maximal in
      an area with relatively low exposure to both infections. CONCLUSIONS: The outcome
      of treating cases of hepatosplenomegaly with praziquantel in this cohort of
      Kenyan children depended strongly on their level of exposure to malaria
      infection. Furthermore, a residual burden of hepatosplenic morbidity was
      observed, which was possibly attributable to the level of exposure to malaria.
      The results suggest that exposure to malaria infection may be a significant
      factor affecting the outcome of praziquantel treatment to reduce the level of
      hepatosplenic morbidity.

PMID- 15450119
TI  - Comparison of misoprostol and dinoprostone for elective induction of labour in
      nulliparous women at full term: a randomized prospective study.
AB  - BACKGROUND: The objective of this randomized prospective study was to compare the
      efficacy of 50 mcg vaginal misoprostol and 3 mg dinoprostone, administered every
      nine hours for a maximum of three doses, for elective induction of labor in a
      specific cohort of nulliparous women with an unfavorable cervix and more than 40
      weeks of gestation. MATERIAL AND METHODS: One hundred and sixty-three pregnant
      women with more than 285 days of gestation were recruited and analyzed. The main
      outcome measures were time from induction to delivery and incidence of vaginal
      delivery within 12 and 24 hours. Admission rate to the neonatal intensive care
      unit within 24 hours post delivery was a secondary outcome. RESULTS: The
      induction-delivery interval was significantly lower in the misoprostol group than
      in the dinoprostone group (11.9 h vs. 15.5 h, p < 0.001). With misoprostol, more
      women delivered within 12 hours (57.5% vs. 32.5%, p < 0.01) and 24 hours (98.7%
      vs. 91.4%, p < 0.05), spontaneous rupture of the membranes occurred more
      frequently (38.8% vs. 20.5%, p < 0.05), there was less need for oxytocin
      augmentation (65.8% vs. 81.5%, p < 0.05) and fewer additional doses were required
      (7.5% vs. 22%, p < 0.05). Although not statistically significant, a lower
      Caesarean section (CS) rate was observed with misoprostol (7.5% vs. 13.3%, p >
      0.05) but with the disadvantage of higher abnormal fetal heart rate (FHR)
      tracings (22.5% vs. 12%, p > 0.05). From the misoprostol group more neonates were
      admitted to the intensive neonatal unit, than from the dinoprostone group (13.5%
      vs. 4.8%, p > 0.05). One woman had an unexplained stillbirth following the
      administration of one dose of dinoprostone. CONCLUSIONS: Vaginal misoprostol,
      compared with dinoprostone in the regimens used, is more effective in elective
      inductions of labor beyond 40 weeks of gestation. Nevertheless, this is at the
      expense of more abnormal FHR tracings and more admissions to the neonatal unit,
      indicating that the faster approach is not necessarily the better approach to
      childbirth.

PMID- 15450120
TI  - The PedsQL Family Impact Module: preliminary reliability and validity.
AB  - BACKGROUND: The PedsQL Measurement Model was designed to measure health-related
      quality of life (HRQOL) in children and adolescents. The PedsQL 4.0 Generic Core
      Scales were developed to be integrated with the PedsQL Disease-Specific Modules.
      The newly developed PedsQL Family Impact Module was designed to measure the
      impact of pediatric chronic health conditions on parents and the family. The
      PedsQL Family Impact Module measures parent self-reported physical, emotional,
      social, and cognitive functioning, communication, and worry. The Module also
      measures parent-reported family daily activities and family relationships.
      METHODS: The 36-item PedsQL Family Impact Module was administered to 23 families
      of medically fragile children with complex chronic health conditions who either
      resided in a long-term care convalescent hospital or resided at home with their
      families. RESULTS: Internal consistency reliability was demonstrated for the
      PedsQL Family Impact Module Total Scale Score (alpha = 0.97), Parent HRQOL
      Summary Score (alpha = 0.96), Family Functioning Summary Score (alpha = 0.90),
      and Module Scales (average alpha = 0.90, range = 0.82 - 0.97). The PedsQL Family
      Impact Module distinguished between families with children in a long-term care
      facility and families whose children resided at home. CONCLUSIONS: The results
      demonstrate the preliminary reliability and validity of the PedsQL Family Impact
      Module in families with children with complex chronic health conditions. The
      PedsQL Family Impact Module will be further field tested to determine the
      measurement properties of this new instrument with other pediatric chronic health
      conditions.

PMID- 15450121
TI  - Use of satellite imagery in constructing a household GIS database for health
      studies in Karachi, Pakistan.
AB  - BACKGROUND: Household-level geographic information systems (GIS) database are
      usually constructed using the geographic positioning system (GPS). In some
      research settings, GPS receivers may fail to capture accurate readings due to
      structural barriers such as tall buildings. We faced this problem when
      constructing a household GIS database for research sites in Karachi, Pakistan
      because the sites are comprised of congested groups of multi-storied building and
      narrow lanes. In order to overcome this problem, we used high resolution
      satellite imagery (IKONOS) to extract relevant geographic information. RESULTS:
      The use of IKONOS satellite imagery allowed us to construct an accurate household
      GIS database, which included the size and orientation of the houses. The GIS
      database was then merged with health data, and spatial analysis of health was
      possible. CONCLUSIONS: The methodological issues introduced in this paper provide
      solutions to the technical barriers in constructing household GIS database in a
      heavily populated urban setting.

PMID- 15450122
TI  - Cytokine and immunoglobulin production by PWM-stimulated peripheral and tumor
      infiltrating lymphocytes of undifferentiated nasopharyngeal carcinoma (NPC)
      patients.
AB  - BACKGROUND: Undifferentiated Nasopharyngeal Carcinoma (NPC) patients show a
      characteristic pattern of antibody responses to the Epstein-Barr virus (EBV)
      which is regularly associated with this tumor. However, no EBV-specific cytotoxic
      activity is detectable by the standard chromium-release assay at both peripheral
      and intratumoral levels. The mechanisms underlying this discrepancy between the
      humoral and cellular immune responses in NPC are still unknown, but might be
      related to an imbalance in immunoregulatory interleukin production. In this
      report, we investigated the ability of peripheral (PBL) and tumor- infiltrating
      (TIL) lymphocytes of undifferentiated NPC patients to produce in vitro three
      interleukins (IL-2, IL-6, IL-10) and three immunoglobulin isotypes (IgM, IgG,
      IgA). METHODS: Lymphocytes from 17 patients and 17 controls were cultured in the
      presence of Pokeweed mitogen (PWM) for 12 days and their culture supernatants
      were tested for interleukins and immunoglobulins by specific enzyme-linked
      immunosorbent assays (ELISA). Data were analysed using Student's t-test and
      probability values below 5% were considered significant. RESULTS: The data
      obtained indicated that TIL of NPC patients produced significantly more IL-2 (p =
      0,0002), IL-10 (p = 0,020), IgM (p= 0,0003) and IgG (p < 0,0001) than their PBL.
      On the other hand, patients PBL produced significantly higher levels of IL-2 (p =
      0,022), IL-10 (p = 0,016) and IgM (p = 0,004) than those of controls. No
      significant differences for IL-6 and IgA were observed. CONCLUSION: Taken
      together, our data reinforce the possibility of an imbalance in immunoregulatory
      interleukin production in NPC patients. An increased ability to produce cytokines
      such as IL-10 may underlie the discrepancy between humoral and cellular immune
      responses characteristic of NPC.

PMID- 15450123
TI  - A comprehensive evaluation of food fortification with folic acid for the primary
      prevention of neural tube defects.
AB  - BACKGROUND: Periconceptional use of vitamin supplements containing folic acid
      reduces the risk of a neural tube defect (NTD). In November 1998, food
      fortification with folic acid was mandated in Canada, as a public health strategy
      to increase the folic acid intake of all women of childbearing age. We undertook
      a comprehensive population based study in Newfoundland to assess the benefits and
      possible adverse effects of this intervention. METHODS: This study was carried
      out in women aged 19-44 years and in seniors from November 1997 to March 1998,
      and from November 2000 to March 2001. The evaluation was comprised of four
      components: I) Determination of rates of NTDs; II) Dietary assessment; III) Blood
      analysis; IV) Assessment of knowledge and use of folic acid supplements. RESULTS:
      The annual rates of NTDs in Newfoundland varied greatly between 1976 and 1997,
      with a mean rate of 3.40 per 1,000 births. There was no significant change in the
      average rates between 1991-93 and 1994-97 (relative risk [RR] 1.01, 95%
      confidence interval [CI] 0.76-1.34). The rates of NTDs fell by 78% (95% CI 65%
      86%) after the implementation of folic acid fortification, from an average of
      4.36 per 1,000 births during 1991-1997 to 0.96 per 1,000 births during 1998-2001
      (RR 0.22, 95% CI 0.14-0.35). The average dietary intake of folic acid due to
      fortification was 70 MUg/day in women aged 19-44 years and 74 MUg/day in seniors.
      There were significant increases in serum and RBC folate levels for women and
      seniors after mandatory fortification. Among seniors, there were no significant
      changes in indices typical of vitamin B12 deficiencies, and no evidence of
      improved folate status masking haematological manifestations of vitamin B12
      deficiency. The proportion of women aged 19-44 years taking a vitamin supplement
      containing folic acid increased from 17% to 28%. CONCLUSIONS: Based on these
      findings, mandatory food fortification in Canada should continue at the current
      levels. Public education regarding folic acid supplement use by women of
      childbearing age should also continue.

PMID- 15450124
TI  - A combinational feature selection and ensemble neural network method for
      classification of gene expression data.
AB  - BACKGROUND: Microarray experiments are becoming a powerful tool for clinical
      diagnosis, as they have the potential to discover gene expression patterns that
      are characteristic for a particular disease. To date, this problem has received
      most attention in the context of cancer research, especially in tumor
      classification. Various feature selection methods and classifier design
      strategies also have been generally used and compared. However, most published
      articles on tumor classification have applied a certain technique to a certain
      dataset, and recently several researchers compared these techniques based on
      several public datasets. But, it has been verified that differently selected
      features reflect different aspects of the dataset and some selected features can
      obtain better solutions on some certain problems. At the same time, faced with a
      large amount of microarray data with little knowledge, it is difficult to find
      the intrinsic characteristics using traditional methods. In this paper, we
      attempt to introduce a combinational feature selection method in conjunction with
      ensemble neural networks to generally improve the accuracy and robustness of
      sample classification. RESULTS: We validate our new method on several recent
      publicly available datasets both with predictive accuracy of testing samples and
      through cross validation. Compared with the best performance of other current
      methods, remarkably improved results can be obtained using our new strategy on a
      wide range of different datasets. CONCLUSIONS: Thus, we conclude that our methods
      can obtain more information in microarray data to get more accurate
      classification and also can help to extract the latent marker genes of the
      diseases for better diagnosis and treatment.

PMID- 15450125
TI  - Protection of pulmonary epithelial cells from oxidative stress by hMYH adenine
      glycosylase.
AB  - BACKGROUND: Oxygen toxicity is a major cause of lung injury. The base excision
      repair pathway is one of the most important cellular protection mechanisms that
      responds to oxidative DNA damage. Lesion-specific DNA repair enzymes include
      hOgg1, hMYH, hNTH and hMTH. METHODS: The above lesion-specific DNA repair enzymes
      were expressed in human alveolar epithelial cells (A549) using the pSF91.1
      retroviral vector. Cells were exposed to a 95% oxygen environment, ionizing
      radiation (IR), or H2O2. Cell growth analysis was performed under non-toxic
      conditions. Western blot analysis was performed to verify over-expression and
      assess endogenous expression under toxic and non-toxic conditions. Statistical
      analysis was performed using the paired Student's t test with significance being
      accepted for p < 0.05. RESULTS: Cell killing assays demonstrated cells over
      expressing hMYH had improved survival to both increased oxygen and IR. Cell
      growth analysis of A549 cells under non-toxic conditions revealed cells over
      expressing hMYH also grow at a slower rate. Western blot analysis demonstrated
      over-expression of each individual gene and did not result in altered endogenous
      expression of the others. However, it was observed that O2 toxicity did lead to a
      reduced endogenous expression of hNTH in A549 cells. CONCLUSION: Increased
      expression of the DNA glycosylase repair enzyme hMYH in A549 cells exposed to O2
      and IR leads to improvements in cell survival. DNA repair through the base
      excision repair pathway may provide an alternative way to offset the damaging
      effects of O2 and its metabolites.

PMID- 15450126
TI  - Evidence-based pharmacotherapy of obsessive-compulsive disorder.
AB  - Obsessive-compulsive disorder is a prevalent and disabling lifespan disorder.
      Clomipramine and the SSRIs have been found to be effective across the range of
      symptoms, both in acute and longer-term studies. Meta-analyses have reported a
      larger treatment effect for clomipramine relative to the SSRIs, but this is not
      supported by evidence from head-to-head comparator studies and, based on their
      superior safety and tolerability, SSRIs are the preferred option for long-term
      treatment in most cases. The treatment-effect is usually gradual and partial, and
      many patients fail to respond adequately to first-line treatment. Pharmacological
      options for refractory cases include switching SRI, increasing the dose, or
      augmenting with an antipsychotic agent. Novel strategies are under investigation
      for this highly morbid group. This paper reviews the key questions related to OCD
      pharmacotherapy, synthesizing evidence derived from randomized controlled trials,
      meta-analyses and consensus guidelines.

PMID- 15450127
TI  - Conditional expression of type I interferon-induced bovine Mx1 GTPase in a stable
      transgenic vero cell line interferes with replication of vesicular stomatitis
      virus.
AB  - In some vertebrate species, type I interferon(IFN)-induced Mx gene expression has
      been shown to confer resistance to some single-stranded RNA (ssRNA) viruses in
      vitro. Because the bovine species is subject to an exceptionally wide array of
      infections caused by such viruses, it is anticipated that an antiviral allele
      should have been retained by evolution at the bovine Mx locus. The identification
      of such allele may help in evaluating the real significance of the Mx genotype
      for disease resistance in vivo, in deciphering host-virus molecular interactions
      involved, or in improving innate disease resistance of livestock through marker
      assisted selection. We validated a double transgenic Vero cell clone in which the
      bovine Mx1 reference allele is placed under control of the human cytomegalovirus
      (CMV) enhancer-promoter sequence containing elements from the bacterial
      tetracycline resistance operon to regulate transcription. In the selected clone,
      transgene repression was very tight, and derepression by doxycycline led to
      homogeneous 48-h duration expression of physiologic levels of bovine Mx1.
      Expression of the transgene caused a dramatic decrease in cytopathic efficiency
      and a 500-5000-fold yield reduction of the Indiana and New Jersey serotypes of
      vesicular stomatitis virus (VSV). To our knowledge, the transgenic clone
      developed here is the first ever reported that allows conditional expression of
      an Mx protein, thus providing a valuable tool for studying functions of Mx
      proteins in general and that of bovine Mx1 in particular. This latter may
      henceforward be included in the group of Mx proteins with authenticated anti-VSV
      activity, which offers new research avenues into the field of host-virus
      interactions.

PMID- 15450128
TI  - Biochemical analyses of multiple fractions of PKR purified from Escherichia coli.
AB  - PKR is a cellular protein kinase activated by double-stranded RNA (dsRNA) that
      phosphorylates eukaryotic initiation factor alpha (eIF2alpha) and inhibits
      protein translation. Activation of PKR is accompanied by Ser/Thr
      autophosphorylation on multiple sites. Because PKR negatively regulates cell
      growth, overexpression and purification of PKR are difficult to achieve. Here, we
      describe overexpression and purification of recombinant PKR protein from
      Escherichia coli under native conditions at the milligram level. Affinity, ion
      exchange, and gel filtration chromatographies revealed multiple fractions of PKR
      with distinctive biochemical characteristics. During gel filtration, a small
      amount of PKR was found in a high molecular weight (>300 kDa) fraction that also
      contained endogenous bacterial RNA. The PKR in this fraction has a constitutive
      substrate phosphorylation activity. The majority of PKR is found in fractions of
      lower molecular weight and is free of RNA but is differentially phosphorylated as
      examined by isoelectric focusing electrophoresis and can be further separated by
      gradient anion exchange chromatography. PKR eluted with low salt has a lower
      level of basal autophosphorylation, and its kinase activity can be induced by
      dsRNA. With an increasing NaCl gradient, the purified PKR exhibits an increased
      level of autophosphorylation and constitutive kinase activity but reduced dsRNA
      inducibility. The highest salt eluent of PKR exhibits little dsRNA-induced
      activation. The inducible activation of high salt eluent PKR by dsRNA can be
      partially restored by treatment with protein phosphatase 1. The production of
      multiple fractions of PKR with different biochemical properties in E. coli
      suggests that the spectrum of PKR activity and regulation in mammalian cells is
      likely to be similarly complex.

PMID- 15450129
TI  - Gender-related association between the TGFB1+869 polymorphism and multiple
      sclerosis.
AB  - Our objective was to investigate whether polymorphisms and haplotypes in the
      TGFB1 gene are associated with susceptibility or disease characteristics of
      multiple sclerosis (MS). In 247 MS patients and 194 controls, single nucleotide
      polymorphisms (SNPs) at position +869 (Leu10Pro) and position +915 (Arg25Pro) in
      the signaling sequence of the TGFB1 gene were determined, and the distribution of
      alleles, genotypes, and haplotypes was related to clinical data. In addition,
      magnetic resonance imaging (MRI) data were studied in a subgroup of patients (n =
      96). The allele distribution of the two polymorphisms studied was in Hardy
      Weinberg equilibrium in patients and in controls. No association was found with
      any of the three haplotypes found in the Dutch population, denoted as haplotype 1
      (TGFB1+869T-TGFB1+915G), haplotype 2 (TGFB1+869C-TGFB1+915G), and haplotype 3
      (TGFB1+869C-TGFB1+915C). However, the TGFB1+869 genotype CC was significantly
      more frequent in patients (p = 0.031, chi2 test). The highest frequency of the
      TGFB1+869 genotype CC was observed in male patients (25.2% vs. 10.0% in controls,
      p = 0.004, chi2 test), and carriership of TGFB1+869 allele C was correspondingly
      increased in male patients (74.8% vs. 56.7%, p = 0.008, chi2 test, OR 2.27, 95%
      CI 1.23-4.17). Although there was no association with clinical markers of disease
      progression, patients homozygous for TGFB1+869 allele C showed a significantly
      higher annual increase in two MRI parameters: ventricular fraction (central
      atrophy) and T1-hypointense lesion load (matrix destruction). The TGFB1 T+869C
      (Leu10Pro) gene polymorphism is associated with MS susceptibility, especially in
      males, and with a more destructive course of the disease as illustrated by MRI.

PMID- 15450131
TI  - Cloning and characterization of Swine interleukin-17, preferentially expressed in
      the intestines.
AB  - Interleukin-17 (IL-17), initially reported as CTLA-8, is a proinflammatory
      cytokine produced mainly by activated T cells. In the present study, the cDNA of
      a swine IL-17 (PoIL-17) gene was cloned from activated neonatal thymocytes, and
      the recombinant PoIL-17 (rPoIL-17) was biologically characterized. The complete
      open reading frame (ORF) of PoIL-17 contains 462-bp coding deduced 153 amino acid
      residues, with a calculated molecular weight of 17.3 kDa. The amino acid sequence
      showed 72.9%, 64.9%, 64.7%, 60.1%, and 47.4% similarities with that of human,
      rat, mouse, Herpesvirus saimiri ORF 13, and chicken, respectively. The six
      cysteine residues conserved over species including the virus were observed in
      PoIL-17. We successfully prepared the recombinant mature form of PoIL-17 and
      analyzed its biologic activities for swine splenocytes. RT-PCR analysis revealed
      a marked upregulation of expression of IL-1beta, IL-8, tumor necrosis factor
      alpha (TNF-alpha), granulocyte colony-stimulating factor (G-CSF), and monocyte
      chemotactic protein-1 (MCP-1) mRNA expression in splenocytes treated with 100
      ng/ml rPoIL-17 for 3 h. Furthermore, a swine chemokine, alveolar macrophage
      derived neutrophil chemotactic factor II (AMCF-II), which was classified into the
      CXC subfamily was also augmented in mRNA level. This evidence indicates that
      recombinat PoIL-17 expressed in Escherichia coli was biologically active and
      exerted similar effects to those of a human (HuIL-17) and murine IL-17 (MuIL-17).
      The PoIL-17 mRNA is strongly expressed in the adult heart, skin, and,
      interestingly, intestinal tissues, including mesenteric lymph nodes but is
      restricted in neonatal tissues by using real-time quantitative RT-PCR. The gene
      sequence and biologically active recombinat protein for PoIL-17 will be useful
      for elucidation of the role of IL-17 in the regulation of intestinal immune
      responses.

PMID- 15450130
TI  - TLR2 and TLR4 stimulation differentially induce cytokine secretion in human
      neonatal, adult, and murine mononuclear cells.
AB  - Toll-like receptor 2 (TLR2) and TLR4 signaling may induce differential secretion
      of T helper 1 (Th1) and Th2 cytokines, potentially influencing the development of
      autoimmune or atopic diseases. To date, the influence of the type of stimulus,
      timing, and dose of TLR2 and TLR4 ligands on cytokine secretion has not been well
      established. We tested whether the innate stimuli peptidoglycan (Ppg, TLR2
      agonist) and lipid A (LpA, TLR4 agonist) differentially affect the secretion of
      interleukin-13 (IL-13) (Th2) and interferon-gamma (IFN-gamma) (Th1). Further, we
      examined the influence of the maturity of the immune system, species, dose, and
      timing of stimuli in human cord and adult peripheral blood mononuclear cells
      (PBMC) and murine cells in vitro and in vivo. Stimulation with Ppg induced the
      secretion of both IL-13 and IFN-gamma, influenced by time and dose in neonates,
      adults, and mice. In contrast, stimulation with LpA induced primarily time
      independent and dose-independent production of IFN-gamma. Pulmonary
      administration of Ppg in vivo in mice resulted in secretion of IL-13, whereas
      administration of LpA resulted in secretion of IFN-gamma in bronchoalveolar
      lavage (BAL). Therefore, TLR2 and TLR4 stimuli differentially influence IL-13 and
      IFN-gamma secretion in neonates, adults, and mice, supporting a critical role for
      innate stimuli in the modulation of cytokine responses.

PMID- 15450132
TI  - The development of a modified human IFN-alpha2b linked to the Fc portion of human
      IgG1 as a novel potential therapeutic for the treatment of hepatitis C virus
      infection.
AB  - Interferon-alpha (IFN-alpha), in conjunction with ribavirin, is the current
      standard for the treatment of chronic hepatitis C virus (HCV) infection. This
      treatment requires frequent dosing, with a significant risk of the development of
      anti-IFN-alpha neutralizing antibodies that correlates with lack of efficacy or
      relapse. We have developed an IFN-alpha linked to the Fc region of human IgG1 for
      improved half-life and less frequent dosing. We have also identified, using a
      human T cell proliferation assay, three regions of IFN-alpha2b that are
      potentially immunogenic, and a variant containing a total of six mutations within
      these regions was made. This variant was made as a fusion to Fc either with or
      without a flexible linker between the fusion partners. Both configurations of the
      variant were less active than native IFN-alpha alone, although the variant
      containing the flexible linker had in vitro antiviral activity within the range
      of other modified IFN-alphas currently in clinical use. Peptides spanning the
      modified regions were tested in T cell proliferation assays and found to be less
      immunogenic than native controls when using peripheral blood mononuclear cells
      (PBMCs) from both healthy individuals and HCV-infected patients who had been
      treated previously with IFN-alpha2b.

PMID- 15450134
TI  - The spike protein of severe acute respiratory syndrome (SARS) is cleaved in virus
      infected Vero-E6 cells.
AB  - Spike protein is one of the major structural proteins of severe acute respiratory
      syndrome-coronavirus. It is essential for the interaction of the virons with host
      cell receptors and subsequent fusion of the viral envelop with host cell membrane
      to allow infection. Some spike proteins of coronavirus, such as MHV, HCoV-OC43,
      AIBV and BcoV, are proteolytically cleaved into two subunits, S1 and S2. In
      contrast, TGV, FIPV and HCoV-229E are not. Many studies have shown that the
      cleavage of spike protein seriously affects its function. In order to investigate
      the maturation and proteolytic processing of the S protein of SARS CoV, we
      generated S1 and S2 subunit specific antibodies (Abs) as well as N, E and 3CL
      protein-specific Abs. Our results showed that the antibodies could efficiently
      and specifically bind to their corresponding proteins from E.coli expressed or
      lysate of SARS-CoV infected Vero-E6 cells by Western blot analysis. Furthermore,
      the anti-S1 and S2 Abs were proved to be capable of binding to SARS CoV under
      electron microscope observation. When S2 Ab was used to perform immune
      precipitation with lysate of SARS-CoV infected cells, a cleaved S2 fragment was
      detected with S2-specific mAb by Western blot analysis. The data demonstrated
      that the cleavage of S protein was observed in the lysate, indicating that
      proteolytic processing of S protein is present in host cells.

PMID- 15450135
TI  - [About PET-CT...].

PMID- 15450136
TI  - [Evaluation of efficacy and clinical impact of FDG-PET in patients with suspicion
      of recurrent colorectal cancer].
AB  - AIMS: To evaluate the utility and clinical impact of Positron Emission Tomography
      with FDG (FDG-PET) in patients with suspected recurrent colorectal cancer (RCR).
      MATERIALS AND METHODS: Eighty five (85) patients with suspicion of RCR (Group A:
      35 for increased tumor markers and negative imaging tests, Group B: 25 operable
      malignant lesions and Group C: 25 with non-conclusive morphological tests) were
      studied retrospectively. In all patients a whole body scan was performed with FDG
      PET. In 29 cases the results were confirmed by histology and clinical evolution
      (follow-up period > 12 months) and imaging test in 56. RESULTS: Prevalence of RCR
      was 89.4 %. FDG-PET was positive in 30/35 patients in Group A, with confirmation
      in 29 cases (PPV: 96.6 %) and 4/5 were true negative (TN) (NPV: 80 %). FDG-PET
      enabled surgery for 6 patients. In Group B, PET was positive in 22/25, and all of
      them had confirmation (PPV: 100 %) but surgery was performed in only 7 patients.
      NPV was 66.6 %. Out of the 25 cases of Group C, FDG-PET obtained 21 TP, 1 FP
      case, 1 TN, 2 FN, and was able to avoid surgery in 8 patients (PPV: 95.4 % and
      NPV: 33.3 %). Overall sensitivity, specificity, PPV, NPV and accuracy were 94.7
      %, 77.7 %, 97.2 %, 63.3 % and 92.9 %, respectively. CONCLUSIONS: FDG-PET has high
      clinical impact in patients with suspicion of recurrent colorectal cancer, and
      should be incorporated in the diagnostic protocols before making a surgery
      decision.

PMID- 15450137
TI  - [Adrenal cortex scintigraphy with and without dexamethasone suppression in the
      study of primary aldosteronism].
AB  - AIM OF THE STUDY: To evaluate the diagnostic performance and efficacy of adrenal
      scintigraphy in primary aldosteronism following the protocol that combines
      adrenal suppression scintigraphy plus non-suppression study. METHODS AND
      PROCEDURES: 20 patients referred to our service with the suspicion of primary
      aldosteronism were studied by combined scintigraphy. Thirteen men and 7 women,
      mean age of 52 years, aged from 31 to 73 years, were included. Uptake of free
      iodine by the thyroid was inhibited by oral Lugol 5 % administration.
      Dexamethasone 4 mg per day was administered from day 7 to the third day of
      detection, when administration was stopped. Adrenal scintigraphy was performed
      after intravenous injection of I-131-norcolesterol (37 MBq). Images were taken at
      24 and/or 48 hours and on the third day. Afterwards, dexamethasone administration
      was stopped and late images on 5th and/or 7th days were obtained. The
      scintigraphic result was confirmed with the final clinical evaluation (FCE) of
      the patient. RESULTS: 11 patients presented pathological studies, 9 adenomas (8TP
      + 1FP) and 2 bilateral adrenal hyperplasia (2TP); 7 normal scintigraphies (6TN
      and 1 non-conclusive FCE) and 2 non-conclusive scintigraphies (1 incidentaloma
      and 1 non-conclusive FCE). Normal adrenal glands were visualized in all cases on
      the 5th and/or 7th day scintigraphy. CONCLUSION: The study of adrenal
      functionalism by the combined protocol of adrenal suppression study plus later
      non-suppression study made it possible to identify with high precision primary
      aldosteronism and to confirm the function of normal adrenal glands.

PMID- 15450138
TI  - [Value of thallium 201-SPECT in typing brain space-occupying lesions].
AB  - OBJECTIVE: This study was designed to assess the diagnostic accuracy of single
      photon emission computed tomography with Tl-201 (SPECT Tl-201) to establish the
      tumoral or non-tumoral nature of brain space occupying lesions in comparison with
      usual diagnostic techniques. MATERIAL AND METHODS: The study population consisted
      of 37 patients, 24 men (64.9 %) and 13 women (35.1 %), mean age 48 +/- 16 years.
      After establishing the clinical and radiological diagnosis of brain lesion, all
      patients underwent SPECT Tl-201, evaluating it only by subjective analysis and
      blinded to neuroestructural techniques. After surgical resection all patients
      were evaluated anatomopathologically to establish the histologic nature. RESULTS:
      The sensitivity of SPECT Tl-201 (0.87) was higher than standard neuroimaging
      techniques (0.78). Specificity (0.43), positive (0.87) and negative (0.43)
      predictive values of SPECT were similar to neuroestructural procedures (MRI and
      CT scan) with 0.43, 0.82 and 0.38 values. Tumoral disease prevalence was 0.81.
      Neuroestructural procedures were non-conclusive in 18.9 % of the studies. No non
      conclusive results were obtained with SPECT Tl-201. CONCLUSIONS: SPECT Tl-201 is
      a diagnostic procedure of high sensitivity to establish the tumoral nature of
      brain lesions, with poor specificity, similar to structural X-ray techniques.

PMID- 15450139
TI  - [Radionuclide cisternography in spontaneous intracranial hypotension syndrome].
AB  - Spontaneous intracranial hypotension (SHI) due to cerebrospinal fluid (CSF) leaks
      is a clinical entity that is being increasingly recognized. Orthostatic headache
      is the cardinal clinical manifestation of this disorder. PATIENTS AND METHOD:
      Seven patients were studied retrospectively because of postural headache
      associated with low CSF pressure. In all patients, radionuclide cisternography as
      well as CT and/or MRI were performed. Radionuclide cisternography was obtained
      after intrathecal injection of radioisotope into the lumbar subarachnoide space.
      Images were obtained at 30 minutes, 2 and 4 hours after the injection. Pledgets
      were inserted into the nose and were considered positive for the presence of CSF
      when the count index of the pledgets regarding a blood sample was > or = 2:1.
      Criteria of spontaneous SHI was the early appearance of bladder activity with
      decrease in the distribution in the cerebral convexity and/or visualization of
      activity in the paraspinal areas. RESULTS: In 5 of the 7 patients scintigraphic
      abnormalities were found. CONCLUSION: Radionuclide cisternography is a reliable
      diagnostic method to diagnose SHI.

PMID- 15450140
TI  - [The stability of solid food labeled with different radiopharmaceuticals for
      studying gastric emptying].
AB  - OBJECTIVE: Sulfur colloid 99mTc-SC, the radiopharmaceutical of choice for solid
      gastric emptying studies, is not available in our country. It has led us to
      assess the solid binding stability of seven alternative radiopharmaceuticals that
      could present adequate fixation to it a priori. MATERIALS AND METHOD: The
      stability of labelled solid food with seven colloidal 99mTc-radiopharmaceuticals
      of different sizes and nature (MAA, tin colloid, rhenium sulphide macrocolloid,
      albumin microcolloid, sulfur nanocolloid, albumin nanocolloid and rhenium sulfur
      nanocolloid) has been studied by measuring their dissociated activity after two
      hours digestion in simulated gastric fluid (kept 120' in agitation, in HCl 0.1 M
      at 37). The survey also assesses radiopharmaceutical labelling stability after
      two hours digestion in identical conditions by measuring their radiochemical
      purity in ITLC. RESULTS: In these conditions, MAA, rhenium sulphide macrocolloid,
      albumin microcolloid and albumin microcolloid present the best behaviour, with an
      activity linked to food over 90 % of the previously fixed activity. CONCLUSIONS:
      According to the results, there is no relationship between the
      radiopharmaceutical size and nature and the stability of its binding to the solid
      food. Because rhenium sulphide macrocolloid is no longer manufactured and the
      other three radiopharmaceuticals which have a binding stability to the solid food
      over 90 % do not include digestive explorations amongst their indications,
      nowadays, there is a serious legal limitation to carry out this type of studies
      in our country.

PMID- 15450141
TI  - Impaired Tc-99m MIBI uptake in the thyroid and parathyroid glands during early
      phase imaging in hemodialysis patients.
AB  - The purpose of this study is to evaluate the possible reasons of an observation
      of diminished uptake of Tc-99m MIBI in the early phase of parathyroid
      scintigraphy in the thyroid and parathyroid glands in patients with chronic renal
      failure who are being evaluated for hyperparathyroidism. Fourteen patients with
      secondary hyperparathyroidism all on hemodialysis with supplement therapy
      consisting of mainly vitamin D and calcium carbonate were studied. Neck and
      mediastinum images obtained at early and late phases were evaluated both visually
      and semiquantitatively. Patients with high PTH levels on hemodialysis showed
      diminished accumulation of radioactivity in the thyroid glands in the early phase
      compared to the soft tissue with a ratio of 1.54 +/- 0.39 (mean +/- std). A
      control group consisting of 10 patients with osteoporosis and Rickets' disease on
      vitamin D therapy was taken as control group A, as well as 11 patients with no
      problems other than cardiac who were not on any medication as control group B and
      8 patients on hemodialysis only with normal PTH levels as control group C.
      Patients in control group A and C showed diminished accumulation of radioactivity
      in the thyroid glands in the early phase compared to the soft tissue with a ratio
      of 1.57 +/- 0.43 and 1.34 +/- 0.13, respectively, while patients in control group
      B showed good uptake 3.18 +/- 0.43. None of the studies showed parathyroid
      pathology. The results of this study show that patients with chronic renal
      failure under hemodialysis treatment are prone to show decreased uptake of the
      radioactivity. Another finding is that vitamin D supplements can cause diminished
      uptake of Tc-99m MIBI. A possible explanation is mentioned in the literature by
      an increase in PGP level and multi-drug resistance, so we suggest that it may
      play a role in impaired Tc-99m MIBI uptake in the thyroid phase and recommend
      cessation of vitamin D3 metabolites before performing parathyroid scintigraphy.

PMID- 15450142
TI  - [FDG-PET in hepatocellular carcinoma. Based on one case].
AB  - We present a case of a 73 year old man, who lost 12 kg of weight in one month,
      had abdominal pain and progressive hepatic failure. A MRI and liver ultrasound
      were performed and, with the patient's symptoms, hepatocellular carcinoma Vs
      metastatic liver was suspected. A PET-FDG was performed and the images showed
      hepatomegaly and splenomegaly, without other findings of interest. FDG
      distribution in the liver was homogeneous. The patient was diagnosed of
      hepatocellular carcinoma after liver biopsy. FDG-PET detects only 50 % to 70 % of
      hepatocellular carcinomas due to varying degrees of activity of the enzyme
      glucose-6-phosphatase in these tumors. This paper reviews the literature on this
      type of situations.

PMID- 15450143
TI  - [Incidental diagnosis of medullary thyroid carcinoma (MTC) after performing 123I
      metaiodobenzylguanidine (123I-MIBG) gammagraphy].
AB  - The objective of this clinical note is to emphasize diagnostic efficiency of 123I
      MIBG scintigraphy in the initial diagnosis and follow-up of medullary thyroid
      carcinoma within MEN2. MATERIALS AND METHODS: We present the case of a patient
      who, during a scintigraphic study with 123I-MIBG for the diagnosis of
      pheochromocytoma, was unexpectedly found to suffer from medullary carcinoma of
      the thyroid. Prior to performing the test, we proceeded to block uptake into the
      thyroid gland through the administration of Lugol. We carried out the
      scintigraphic study by intravenously injecting 370 MBq 123I-MIBG. RESULTS: A
      pathological uptake of the radiopharmaceutical compound over the right suprarenal
      gland, and unexpectedly, over the thyroid gland was detected, thus confirming the
      existence of medullary carcinoma of the thyroid in this patient, and obtaining
      the diagnosis of Type MEN2A polyglandular syndrome. CONCLUSIONS: From our
      experience, we can manifest the value of scintigraphy using 123I-MIBG in the
      diagnosis and localization of medullary carcinoma of the thyroid. Furthermore, it
      is indicated in patients suspected of MEN, since it makes it possible to reach a
      diagnosis of this kind of syndrome through the performance of just one test.

PMID- 15450144
TI  - [Diagnosis of bone infection with 99mTc-ceftizoxime].

PMID- 15450145
TI  - [Pediatric reflex sympathetic dystrophy].

PMID- 15450146
TI  - [Clinical impact of PET in pediatrics].

PMID- 15450147
TI  - [Studies of results in pulmonary thromboembolism: from the clinical practice to
      scientific evidence].

PMID- 15450148
TI  - [Evidence-based medicine versus experience-based medicine].

PMID- 15450150
TI  - [Assessment of practice competence and scientific knowledge of ICU nurses in the
      tracheal suctioning].
AB  - Tracheal suctioning is essential to maintain permeability of the artificial
      airway. This procedure may be associated to risks for the patients. Thus, it is
      very important to know if the nurses perform it correctly and if the practice is
      based on scientific evidence. This investigations objectives are: evaluate
      practical competence of the nurses, as well as the scientific knowledge that they
      have on this procedures in a Polyvalent Intensive Care Unit and analyze if there
      are discrepancies between the practice competence and scientific knowledge. This
      descriptive study, performed in 34 nurses, analyzed the performance of tracheal
      suctioning by direct observation, using the data collection of a structured grid
      that included 19 aspects to evaluate, grouped into 6 categories. In the same way,
      knowledge on the procedure was analyzed, using a 19-item self-administered
      questionnaire, also grouped into 6 categories, which evaluated the same aspects
      observed. The total mean score obtained in the practice observation grid (P) was
      12.09 for a maximum score of 19, while it was 14.24 in the knowledge
      questionnaire (Q). When analyzed by categories, discrepancies were obtained in
      the following aspects: in the need for hand washing prior to suctioning (P =
      55.9%; Q = 97.1%), in cleaning of the suction catheter after each suctioning
      during the procedure (P = 0%; Q = 38.2%), in the correct performance of
      hyperoxygenation and hyperinsuflation, before, during and after the procedure (P
      = 11.8%; Q = 941%), in the correct selection of the size suction catheter in
      relationship with endotracheal tubes internal lumen (P = 0%; Q = 52.9%), in the
      maximum time the catheter remains in the trachea (P = 100%; Q = 23.5%), in the
      maximum number of times that the catheter should be introduced in each suctioning
      (P = 100%; Q = 73.5%) and in the non-instillation of saline solution (P = 29.4%;
      Q = 58.8%). When the total scores obtained were compared, both in practice and
      knowledge, with the years of experience in ICU, no statistically significant
      differences were found. It is concluded that the study nurses have scientific
      knowledge of the suctioning procedure that are better than their practice
      competence. Discrepancies between practice and knowledge were also found in
      several of the aspects evaluated, which orients towards the specific needs of
      training in this procedure.

PMID- 15450151
TI  - [Pressure sores secondary to immobilization with cervical collar: a complication
      of acute cervical injury].
AB  - Cervical collars are essential in the treatment of patients with suspicion or
      verification of acute cervical spine injury (ACSI). One of the complications of
      these devices is the development of pressure scores (PS). This study aims to
      determine its incidence in our unit, the characteristics of patients with ACSI
      who suffer PS due to the collar and to describe aspects related with these
      injuries. We include 92 patients with ACSI hospitalized more than 24 hours from
      January 2002 to December 2003. We analyze demographic variables, incidence, risk
      factors and characteristics of the PS that develop. The incidence of these
      lesions was 23.9%. Patients with PS presented: a higher injury severity score
      (ISS) (37.5 9.8 vs. 31.3 14.9), a greater percentage of catheter carriers of
      intracraneal pressure (ICP) (55.6% vs. 16.2%), longer time of mechanical
      ventilation (15.4 8.2 vs. 6.1 9) and longer stays (24.6 10.9 vs. 10 10.3), all
      statistically significant (p< 0.05). A total of 38 PS were detected, 7 (RI 5
      13.8) being the median of the detection day. The chin, occipital and
      suprascapular zone were the most frequent locations. A total of 42.1% were grade
      II and 39.5% grade III. The occipital injuries were the most serious and those
      detected the latest. We conclude that a high index of suspicion of PS due to
      collar in patients with ACSI, elevated ISS, monitoring of ICP, mechanical
      ventilation and prolonged stays is required. The occipital zone requires special
      attention due to the seriousness of the injuries recorded. We suggest a specific
      multidisciplinary protocol for this problem.

PMID- 15450152
TI  - [Measurement of minimum disposable volume in the extraction of an analysis
      through an arterial catheter].
AB  - OBJECTIVE: Arterial catheters are used to extract blood samples. To maintain its
      permeability we use heparin solution, which may contaminate and alter the desired
      results. Our aim was to determine the volume of the minimum discards during blood
      extractions to avoid results that might be altered in the analysis of
      biochemistry. MATERIAL AND METHODS: A prospective study was carried out in 18
      beds intensive care unit. Patients with arterial catheter (Seldicath) were
      included, maintaining 500 UI of heparin in saline of 500 ml, at a pressure of 300
      mmHg through pressurizer (Tycos). The dead space (DS) in the radial arterial
      system is 0.8 ml and 1 ml in the femoral. We analyzed the reliability of
      different discards comparing the following: 3 ml + DS, 7.5 ml + DS, 12 ml + DS
      and 16.5 ml + DS. The statistical analysis was carried out through ANOVA and t
      Student. RESULTS: In biochemistry, significant differences were not found except
      for potasium (p< 0.001) with 3 ml+DS during control, although it is not
      clinically relevant [difference through = 0.1 mEq/l (DS 0.2)]. Significant
      differences in prothrombina (p = 0.004) were found in coagulation, comparing 3
      ml+DS and 16.5 ml + DS and in cefaline, comparing 7.5 ml + DS (p< 0.0001) and
      16.5 ml + DS. There were not significant differences in the studies of gases.
      CONCLUSIONS: Our study shows that to reach a reliable analytical results, it is
      not necessary to discard more than 3 ml+DS in biochemistry and in blood gases,
      and to determine cefalina time would necessary to discard a minimum of 7.5 ml+DS.

PMID- 15450156
TI  - LTP and LTD: an embarrassment of riches.
AB  - LTP and LTD, the long-term potentiation and depression of excitatory synaptic
      transmission, are widespread phenomena expressed at possibly every excitatory
      synapse in the mammalian brain. It is now clear that "LTP" and "LTD" are not
      unitary phenomena. Their mechanisms vary depending on the synapses and circuits
      in which they operate. Here we review those forms of LTP and LTD for which
      mechanisms have been most firmly established. Examples are provided that show how
      these mechanisms can contribute to experience-dependent modifications of brain
      function.

PMID- 15450157
TI  - Spike timing-dependent plasticity of neural circuits.
AB  - Recent findings of spike timing-dependent plasticity (STDP) have stimulated much
      interest among experimentalists and theorists. Beyond the traditional correlation
      based Hebbian plasticity, STDP opens up new avenues for understanding information
      coding and circuit plasticity that depend on the precise timing of neuronal
      spikes. Here we summarize experimental characterization of STDP at various
      synapses, the underlying cellular mechanisms, and the associated changes in
      neuronal excitability and dendritic integration. We also describe STDP in the
      context of complex spike patterns and its dependence on the dendritic location of
      the synapse. Finally, we discuss timing-dependent modification of neuronal
      receptive fields and human visual perception and the computational significance
      of STDP as a synaptic learning rule.

PMID- 15450158
TI  - Olfactory learning.
AB  - The olfactory nervous systems of insects and mammals exhibit many similarities,
      suggesting that the mechanisms for olfactory learning may be shared. Neural
      correlates of olfactory memory are distributed among many neurons within the
      olfactory nervous system. Perceptual olfactory learning may be mediated by
      alterations in the odorant receptive fields of second and/or third order
      olfactory neurons, and by increases in the coherency of activity among ensembles
      of second order neurons. Operant olfactory conditioning is associated with an
      increase in the coherent population activity of these neurons. Olfactory
      classical conditioning increases the odor responsiveness and synaptic activity of
      second and perhaps third order neurons. Operant and classical conditioning both
      produce an increased responsiveness to conditioned odors in neurons of the
      basolateral amygdala. Molecular genetic studies of olfactory learning in
      Drosophila have revealed numerous molecules that function within the third order
      olfactory neurons for normal olfactory learning.

PMID- 15450159
TI  - The persistence of long-term memory: a molecular approach to self-sustaining
      changes in learning-induced synaptic growth.
AB  - Recent cellular and molecular studies of both implicit and explicit memory
      storage suggest that experience-dependent modulation of synaptic strength and
      structure is a fundamental mechanism by which these diverse forms of memory are
      encoded and stored. For both forms of memory storage, some type of synaptic
      growth is thought to represent the stable cellular change that maintains the long
      term process. In this review, we discuss recent findings on the molecular events
      that underlie learning-related synaptic growth in Aplysia and discuss the
      possibility that an active, prion-based mechanism is important for the
      maintenance of the structural change and for the persistence of long-term memory.

PMID- 15450160
TI  - Translational regulatory mechanisms in persistent forms of synaptic plasticity.
AB  - Memory and synaptic plasticity exhibit distinct temporal phases, with long
      lasting forms distinguished by their dependence on macromolecular synthesis.
      Prevailing models for the molecular mechanisms underlying long-lasting synaptic
      plasticity have largely focused on transcriptional regulation. However, a growing
      body of evidence now supports a crucial role for neuronal activity-dependent mRNA
      translation, which may occur in dendrites for a subset of neuronal mRNAs. Recent
      work has begun to define the signaling mechanisms coupling synaptic activation to
      the protein synthesis machinery. The ERK and mTOR signaling pathways have been
      shown to regulate the activity of the general translational machinery, while the
      translation of particular classes of mRNAs is additionally controlled by gene
      specific mechanisms. Rapid enhancement of the synthesis of a diverse array of
      neuronal proteins through such mechanisms provides the components necessary for
      persistent forms of LTP and LTD. These findings have important implications for
      the synapse specificity and associativity of protein synthesis-dependent changes
      in synaptic strength.

PMID- 15450161
TI  - Molecular mechanisms underlying emotional learning and memory in the lateral
      amygdala.
AB  - Fear conditioning is a valuable behavioral paradigm for studying the neural basis
      of emotional learning and memory. The lateral nucleus of the amygdala (LA) is a
      crucial site of neural changes that occur during fear conditioning.
      Pharmacological manipulations of the LA, strategically timed with respect to
      training and testing, have shed light on the molecular events that mediate the
      acquisition of fear associations and the formation and maintenance of long-term
      memories of those associations. Similar mechanisms have been found to underlie
      long-term potentiation (LTP) in LA, an artificial means of inducing synaptic
      plasticity and a physiological model of learning and memory. Thus, LTP-like
      changes in synaptic plasticity may underlie fear conditioning. Given that the
      neural circuit underlying fear conditioning has been implicated in emotional
      disorders in humans, the molecular mechanisms of fear conditioning are potential
      targets for psychotherapeutic drug development.

PMID- 15450162
TI  - Rites of passage of the engram: reconsolidation and the lingering consolidation
      hypothesis.
AB  - Memory consolidation refers to the progressive stabilization of items in long
      term memory as well as to the memory phase(s) during which this stabilization
      takes place. The textbook account is that, for each item in memory, consolidation
      starts and ends just once. In recent years, however, the notion that memories
      reconsolidate upon their reactivation and hence regain sensitivity to amnestic
      agents has been revitalized. This issue is of marked theoretical and clinical
      interest. Here we review the recent literature on reconsolidation and infer, on
      the basis of the majority of the data, that blockade of reconsolidation does not
      induce permanent amnesia. Further, in several systems, reconsolidation occurs
      only in relatively fresh memories. We propose a framework model, which interprets
      reconsolidation as a manifestation of lingering consolidation, rather than
      recapitulation of a process that had already come to a closure. This model
      reflects on the nature of consolidation in general and makes predictions that
      could guide further research.

PMID- 15450163
TI  - New circuits for old memories: the role of the neocortex in consolidation.
AB  - Studies of learning and memory have provided a great deal of evidence implicating
      hippocampal mechanisms in the initial storage of facts and events. However, until
      recently, there were few hints as to how and where this information was
      permanently stored. A recent series of rodent molecular and cellular cognition
      studies provide compelling evidence for the involvement of specific neocortical
      regions in the storage of information initially processed in the hippocampus.
      Areas of the prefrontal cortex, including the anterior cingulate and prelimbic
      cortices, and the temporal cortex show robust increases in activity specifically
      following remote memory retrieval. Importantly, damage to or inactivation of
      these areas produces selective remote memory deficits. Additionally, transgenic
      studies provide glimpses into the molecular and cellular mechanisms underlying
      cortical memory consolidation. The studies reviewed here represent the first
      exciting steps toward the understanding of the molecular, cellular, and systems
      mechanisms of how the brain stores our oldest and perhaps most defining memories.

PMID- 15450164
TI  - Hippocampus: cognitive processes and neural representations that underlie
      declarative memory.
AB  - The hippocampus serves a critical role in declarative memory--our capacity to
      recall everyday facts and events. Recent studies using functional brain imaging
      in humans and neuropsychological analyses of humans and animals with hippocampal
      damage have revealed some of the elemental cognitive processes mediated by the
      hippocampus. In addition, recent characterizations of neuronal firing patterns in
      behaving animals and humans have suggested how neural representations in the
      hippocampus underlie those elemental cognitive processes in the service of
      declarative memory.

PMID- 15450165
TI  - Sleep-dependent learning and memory consolidation.
AB  - While the functions of sleep remain largely unknown, one of the most exciting and
      contentious hypotheses is that sleep contributes importantly to memory. A large
      number of studies offer a substantive body of evidence supporting this role of
      sleep in what is becoming known as sleep-dependent memory processing. This review
      will provide evidence of sleep-dependent memory consolidation and sleep-dependent
      brain plasticity and is divided into five sections: (1) an overview of sleep
      stages, memory categories, and the distinct stages of memory development; (2) a
      review of the specific relationships between sleep and memory, both in humans and
      animals; (3) a survey of evidence describing sleep-dependent brain plasticity,
      including human brain imaging studies as well as animal studies of cellular
      neurophysiology and molecular biology. We close (4) with a consideration of
      unanswered questions as well as existing arguments against the role of sleep in
      learning and memory and (5) a concluding summary.

PMID- 15450166
TI  - Memory consolidation in sleep; dream or reality.
AB  - We discuss several lines of evidence refuting the hypothesis that procedural or
      declarative memories are processed/consolidated in sleep. One of the strongest
      arguments against a role for sleep in declarative memory involves the
      demonstration that the marked suppression or elimination of REM sleep in subjects
      on antidepressant drugs or with brainstem lesions produces no detrimental effects
      on cognition. Procedural memory, like declarative memory, undergoes a slow, time
      dependent period of consolidation. A process has recently been described wherein
      performance on some procedural tasks improves with the mere passage of time and
      has been termed "enhancement." Some studies, but not others, have reported that
      the consolidation/enhancement of perceptual and motor skills is dependent on
      sleep. We suggest that consolidation or enhancement, initiated in waking with
      task acquisition, could in some instances extend to sleep, but sleep would serve
      no unique role in these processes. In sum, there is no compelling evidence to
      support a relationship between sleep and memory consolidation.

PMID- 15450167
TI  - The cognitive neuroscience of memory distortion.
AB  - Memory distortion occurs in the laboratory and in everyday life. This article
      focuses on false recognition, a common type of memory distortion in which
      individuals incorrectly claim to have encountered a novel object or event. By
      considering evidence from neuropsychology, neuroimaging, and electrophysiology,
      we address three questions. (1) Are there patterns of neural activity that can
      distinguish between true and false recognition? (2) Which brain regions
      contribute to false recognition? (3) Which brain regions play a role in
      monitoring or reducing false recognition? Neuroimaging and electrophysiological
      studies suggest that sensory activity is greater for true recognition compared to
      false recognition. Neuropsychological and neuroimaging results indicate that the
      hippocampus and several cortical regions contribute to false recognition.
      Evidence from neuropsychology, neuroimaging, and electrophysiology implicates the
      prefrontal cortex in retrieval monitoring that can limit the rate of false
      recognition.

PMID- 15450168
TI  - Memory and addiction: shared neural circuitry and molecular mechanisms.
AB  - An important conceptual advance in the past decade has been the understanding
      that the process of drug addiction shares striking commonalities with neural
      plasticity associated with natural reward learning and memory. Basic mechanisms
      involving dopamine, glutamate, and their intracellular and genomic targets have
      been the focus of attention in this research area. These two neurotransmitter
      systems, widely distributed in many regions of cortex, limbic system, and basal
      ganglia, appear to play a key integrative role in motivation, learning, and
      memory, thus modulating adaptive behavior. However, many drugs of abuse exert
      their primary effects precisely on these pathways and are able to induce enduring
      cellular alterations in motivational networks, thus leading to maladaptive
      behaviors. Current theories and research on this topic are reviewed from an
      integrative systems perspective, with special emphasis on cellular, molecular,
      and behavioral aspects of dopamine D-1 and glutamate NMDA signaling, instrumental
      learning, and drug cue conditioning.

PMID- 15450169
TI  - Deciphering the molecular basis of memory failure in Alzheimer's disease.
AB  - Acutely developing lesions of the brain have been highly instructive in
      elucidating the neural systems underlying memory in humans and animal models.
      Much less has been learned from chronic neurodegenerative disorders that
      insidiously impair memory. But the advent of a detailed molecular hypothesis for
      the development of Alzheimer's disease and the creation of compelling mouse
      models thereof have begun to change this situation. Experiments in rodents
      suggest that soluble oligomers of the amyloid beta protein (Abeta) may discretely
      interfere with synaptic mechanisms mediating aspects of learning and memory,
      including long-term potentiation. In humans, memory impairment correlates
      strongly with cortical levels of soluble Abeta species, which include oligomers.
      Local inflammatory changes, neurofibrillary degeneration, and neurotransmitter
      deficits all contribute to memory impairment, but available evidence suggests
      that these develop as a consequence of early Abeta accumulation. Accordingly,
      attempts to slow memory and cognitive loss by decreasing cerebral Abeta levels
      have entered human trials.

PMID- 15450170
TI  - Memory and executive function in aging and AD: multiple factors that cause
      decline and reserve factors that compensate.
AB  - Memory decline in aging results from multiple factors that influence both
      executive function and the medial temporal lobe memory system. In advanced aging,
      frontal-striatal systems are preferentially vulnerable to white matter change,
      atrophy, and certain forms of neurotransmitter depletion. Frontal-striatal change
      may underlie mild memory difficulties in aging that are most apparent on tasks
      demanding high levels of attention and controlled processing. Through separate
      mechanisms, Alzheimer's disease preferentially affects the medial temporal lobe
      and cortical networks, including posterior cingulate and retrosplenial cortex
      early in its progression, often before clinical symptoms are recognized.
      Disruption of the medial temporal lobe memory system leads directly to memory
      impairment. Recent findings further suggest that age-associated change is not
      received passively. Reliance on reserve is emerging as an important factor that
      determines who ages gracefully and who declines rapidly. Functional imaging
      studies, in particular, suggest increased recruitment of brain areas in older
      adults that may reflect a form of compensation.

PMID- 15450171
TI  - Cytotoxic ribosome-inactivating lectins from plants.
AB  - A class of heterodimeric plant proteins consisting of a carbohydrate-binding B
      chain and an enzymatic A-chain which act on ribosomes to inhibit protein
      synthesis are amongst the most toxic substances known. The best known example of
      such a toxic lectin is ricin, produced by the seeds of the castor oil plant,
      Ricinnus communis. For ricin to reach its substrate in the cytosol, it must be
      endocytosed, transported through the endomembrane system to reach the compartment
      from which it is translocated into the cytosol, and there avoid degradation
      making it possible for a few molecules to inactivate a large proportion of the
      ribosomes and hence kill the cell. Cell entry by ricin involves the following
      steps: (i) binding to cell-surface glycolipids and glycoproteins bearing beta-1,4
      linked galactose residues through the lectin activity of the B-chain (RTB); (ii)
      uptake by endocytosis and entry into early endosomes; (iii) transfer by vesicular
      transport to the trans-Golgi network; (iv) retrograde vesicular transport through
      the Golgi complex and into the endoplasmic reticulum (ER); (v) reduction of the
      disulfide bond connecting the A- and B-chains; (vi) a partial unfolding of the A
      chain (RTA) to enable it to translocate across the ER membrane via the Sec61p
      translocon using the pathway normally followed by misfolded ER proteins for
      targeting to the ER-associated degradation (ERAD) machinery; (vi) refolding in
      the cytosol into a protease-resistant, enzymatically active structure; (vii)
      interaction with the sarcin-ricin domain (SRD) of the large ribosome subunit RNA
      followed by cleavage of a single N-glycosidic bond in the RNA to generate a
      depurinated, inactive ribosome. In addition to the highly specific action on
      ribosomes, ricin and related ribosome-inactivating proteins (RIPs) have a less
      specific action in vitro on DNA and RNA substrates releasing multiple adenine,
      and in some instances, guanine residues. This polynucleotide:adenosine
      glycosidase activity has been implicated in the general antiviral, and
      specifically, the anti HIV-1 activity of several single-chain RIPs which are
      homologous to the A-chains of the heterodimeric lectins. However, in the absence
      of clear cause and effect evidence in vivo, such claims should be regarded with
      caution.

PMID- 15450172
TI  - DNA binding properties of protein TrwA, a possible structural variant of the Arc
      repressor superfamily.
AB  - Conjugative DNA processing of plasmid R388 requires the concerted action of two
      proteins, the relaxase-helicase TrwC and the relaxase enhancer TrwA. TrwA can be
      aligned with DNA binding proteins belonging to the ribbon-helix-helix (RHH)
      protein family. To further analyse TrwA function, the structural domains of the
      protein have been identified and dissected by limited proteolysis. Two stable
      domains were found that resulted to be, according to DNA binding experiments and
      oligomerization analysis, an N-terminal DNA binding domain and a C-terminal
      tetramerization domain. Using the three-dimensional structure of the Arc
      repressor as a guide, it was possible to model TrwA DNA binding site with atomic
      detail. As a result, TrwA polar amino acids Q8, R10 and S12, contained in the
      polar face of a putative N-terminal beta-strand, were found to be directly
      involved in DNA binding, in a manner analogous to RHH proteins. In this respect,
      TrwA seemed to be a new member of the RHH family. However, secondary structure
      analyses underscored the existence of a substantial difference in the
      architecture of the TrwA-oriT complex when compared to the Arc repressor-operator
      complex.

PMID- 15450173
TI  - Localization of a pH-dependent, A2 subunit-interactive surface within the factor
      VIIIa A1 subunit.
AB  - Factor VIIIa can be reconstituted from A2 subunit and A1/A3-C1-C2 dimer in a
      reaction that is facilitated by slightly acidic pH. We recently demonstrated that
      a truncated A1 (A1(37-336)) possessed markedly reduced affinity for A2 compared
      with intact A1, but retained 30% of native factor VIIIa activity in the presence
      of A3-C1-C2. We now identify A1-interactive regions for A2 using A1 fragments
      derived from a limited tryptic digest. Unfractionated trypsin-cleaved A1
      inhibited reconstituted factor VIIIa activity. Two fragments, designated A1(37
      121) and A1(221-336), markedly inhibited factor VIIIa reconstitution with either
      native A1 (K(i)=340 and 194 nM, respectively) or with A1(37-336) (K(i)=69 and 116
      nM, respectively) at pH 6.0. A third fragment designated A1(122-206) did not
      possess inhibitory activity. At pH 7.2, the A1(221-336) partially inhibited
      reconstitution, whereas the A1(37-121) possessed little if any inhibitory
      activity. Both fragments inhibited factor VIIIa reconstitution as judged by
      fluorescence energy transfer using acrylodan-labeled A2 and fluorescein-labeled
      A1 forms at pH 6.0. Furthermore, covalent cross-linking between A2 and A1(37-121)
      but not A1(221-336) was observed following reaction with a zero-length cross
      linker. These findings demonstrate the presence of an extended, pH-dependent A2
      interactive surface within regions 37-121 and 221-336 of A1. This interactive
      surface appears conformationally labile in the truncated A1 as judged by its
      apparent stabilization following association with A3-C1-C2.

PMID- 15450174
TI  - Unique ligation properties of eukaryotic NAD+-dependent DNA ligase from
      Melanoplus sanguinipes entomopoxvirus.
AB  - The eukaryotic Melanoplus sanguinipes entomopoxvirus (MsEPV) genome reveals a
      homologous sequence to eubacterial nicotinamide adenine dinucleotide (NAD(+))
      dependent DNA ligases [J. Virol. 73 (1999) 533]. This 522-amino acid open reading
      frame (ORF) contains all conserved nucleotidyl transferase motifs but lacks the
      zinc finger motif and BRCT domain found in conventional eubacterial NAD(+)
      ligases. Nevertheless, cloned MsEPV ligase seals DNA nicks in a NAD(+)-dependent
      fashion, while adenosine 5'-monophosphate (ATP) cannot serve as an adenylation
      cofactor. The ligation activity of MsEPV ligase requires Mg(2+) or Mn(2+). MsEPV
      ligase seals sticky ends efficiently, but has little activity on 1-nucleotide gap
      or blunt-ended DNA substrates even in the presence of polyethylene glycol. In
      comparison, bacterial NAD(+)-dependent ligases seal blunt-ended DNA substrates in
      the presence of polyethylene glycol. MsEPV DNA ligase readily joins DNA nicks
      with mismatches at either side of the nick junction, except for mismatches at the
      nick junction containing an A base in the template strand (A/A, G/A, and C/A).
      MsEPV NAD(+)-dependent DNA ligase can join DNA probes on RNA templates, a unique
      property that distinguishes this enzyme from other conventional bacterial NAD(+)
      DNA ligases. T4 ATP-dependent DNA ligase shows no detectable mismatch ligation at
      the 3' side of the nick but substantial 5' T/G mismatch ligation on an RNA
      template. In contrast, MsEPV ligase joins mismatches at the 3' side of the nick
      more frequently than at the 5' side of the nick on an RNA template. The
      complementary specificities of these two enzymes suggest alternative primer
      design for genomic profiling approaches that use allele-specific detection
      directly from RNA transcripts.

PMID- 15450175
TI  - Probing a hydrogen bond pair and the FAD redox properties in the proline
      dehydrogenase domain of Escherichia coli PutA.
AB  - The PutA flavoprotein from Escherichia coli combines DNA-binding, proline
      dehydrogenase (PRODH), and Delta(1)-pyrroline-5-carboxylate dehydrogenase (P5CDH)
      activities onto a single polypeptide. Recently, an X-ray crystal structure of
      PutA residues 87-612 was solved which identified a D370-Y540 hydrogen bond pair
      in the PRODH active site that appears to have an important role in shaping
      proline binding and the FAD redox environment. To examine the role of D370-Y540
      in the PRODH active site, mutants D370A, Y540F, and D370A/Y540F were
      characterized in a form of PutA containing only residues 86-601 (PutA86-601)
      designed to mimic the known structural region of PutA (87-612). Disruption of the
      D370-Y540 pair only slightly diminished k(cat), while more noticeable affects
      were observed in K(m). The mutant D370A/Y540F showed the most significant changes
      in the pH dependence of k(cat)/K(m) and K(m) relative to wild-type PutA86-601
      with an apparent pK(a) value of about 8.2 for the pH-dependent decrease in K(m).
      From the pH profile of D370A/Y540F inhibition by l-tetrahydro-2-furoic acid (l
      THFA), the pH dependency of K(m) in D370A/Y540F is interpreted as resulting from
      the deprotonation of the proline amine in the E-S complex. Replacement of D370
      and Y540 produces divergent effects on the E(m) for bound FAD. At pH 7.0, E(m)
      values of -0.026, -0.089 and -0.042 V were determined for the two-electron
      reduction of bound FAD in D370A, Y540F and D370A/Y540F, respectively. The 40-mV
      positive shift in E(m) determined for D370A relative to wild-type PutA86-601
      (E(m)=-0.066 V, pH 7.0) indicates D370 has a key role in modulating the FAD redox
      environment.

PMID- 15450176
TI  - Dihydropyrimidine dehydrogenase: a flavoprotein with four iron-sulfur clusters.
AB  - Dihydropyrimidine dehydrogenase (DPD) is the first and rate-limiting enzyme in
      the pathway for degradation of pyrimidines, responsible for the reduction of the
      5,6-double bond to give the dihydropyrimidine using NADPH as the reductant. The
      enzyme is a dimer of 220 kDa, and each monomer contains one FAD, one FMN, and
      four FeS clusters. The FAD is situated at one end of the protein, the FMN is at
      the other, and four FeS clusters form a conduit for electron transfer between the
      two sites comprised of two FeS clusters from each monomer. The enzyme has a two
      site ping-pong mechanism with NADPH reducing FAD and reduced FMN responsible for
      reducing the pyrimidine. Solvent deuterium kinetic isotope effects indicate a
      rate-limiting reduction of FAD accompanied by pH-dependent structural
      rearrangement for proper orientation of the nicotinamide ring. Transfer of
      electrons from site 1 to site 2 is downhill with FMN rapidly reduced by FADH(2)
      via the FeS conduit. The reduction of the pyrimidine at site 2 proceeds using
      general acid catalysis with protonation at N5 of FMN carried out by K574 as FMN
      is reduced and protonation at C5 of the pyrimidine by C671 as it is reduced.
      Kinetic isotope effects indicate a stepwise reaction for reduction of the
      pyrimidine with hydride transfer at C6 preceding proton transfer at C5, with a
      late transition state for the proton transfer step.

PMID- 15450177
TI  - Solution 1H NMR study of the active site molecular structure and magnetic
      properties of the cyanomet complex of the isolated, tetrameric beta-chain from
      human adult hemoglobin.
AB  - The solution molecular structure and the electronic and magnetic properties of
      the heme pocket of the cyanomet complex of the isolated beta-chain of human adult
      hemoglobin, HbA, have been investigated by homonuclear 2D (1)H NMR in order to
      assess the extent of assignments allowed by (1)H NMR of a homo-tetrameric 65-kDa
      protein, to guide the future assignments of the heterotetrameric complex of HbA,
      and to compare the structure of the beta-chain to the crystallographically
      characterized complexes that contains the beta-chain. The target residues are
      those that exhibit significant (>|0.2| ppm) dipolar shifts, as predicted by a
      "preliminary" set of magnetic axes determined from a small set of easily assigned
      active site residues. All 104 target residues ( approximately 70% of total) were
      assigned by taking advantage of the temperature dependence predicted by the
      "preliminary" magnetic axes for the polypeptide backbone; they include all
      residues proposed to play a significant role in modulating the ligand affinity in
      the tetramer HbA. Left unassigned are the A-helix, the end of the G-helix and the
      beginning of the H-helix where dipolar shifts are less than |0.2| ppm. These
      comprehensive assignments allow the determination of a robust set of orientation
      and anisotropies of the paramagnetic susceptibility tensor that leads to
      quantitative interpretation of the dipolar shifts of the beta-chain in terms of
      the crystal coordinates of the beta-subunit in ligated HbA which, in turn,
      confirms a largely conserved molecular structure of the isolated beta-chain
      relative to that in the intact R-state HbA. The major magnetic axis, which is
      correlated with the tilt of the Fe-CN unit, is tilted approximately 10 degrees
      from the heme normal so that the Fe-CN unit is tilted toward the beta-meso-H in a
      fashion remarkably similar to the Fe-CO tilt in the beta-subunit of HbCO. It is
      concluded that a set of "preliminary" magnetic axes and the use of variable
      temperature 2D NMR spectra are crucial to effective assignments in the tetrameric
      cyanomet beta-chain and that this approach should be similarly effective in HbA.

PMID- 15450178
TI  - Characterization of pancreatic lipase-related protein 2 isolated from human
      pancreatic juice.
AB  - Human pancreatic lipase-related protein 2 (HPLRP2) was identified for the first
      time in pancreatic juice using specific anti-peptide antibodies and purified to
      homogeneity. Antibodies were raised in the rabbit using a synthetic peptide from
      the HPLRP2 protein sequence deduced from cDNA. Western blotting analysis showed
      that these antibodies did not react with classical human pancreatic lipase (HPL)
      or human pancreatic lipase-related protein 1 (HPLRP1) but cross-reacted with
      native rat PLRP2 (RPLRP2), as well as with recombinant rat and guinea-pig PLRP2
      (GPLRP2). Immunoaffinity chromatography was performed on immobilized anti
      recombinant HPLRP2 polyclonal antibodies to purify native HPLRP2 after
      conventional chromatographic steps including gel filtration and chromatrography
      on an anion-exchanger. The substrate specificity of HPLRP2 was investigated using
      various triglycerides, phospholipids and galactolipids as substrates. The lipase
      activity on triglycerides was inhibited by bile salts and weakly restored by
      colipase. The phospholipase activity of HPLRP2 on phospholipid micelles was very
      low. A significant level of galactolipase activity was measured using
      monogalactosyldiglyceride monomolecular films. These data suggest that the main
      physiological function of HPLRP2 is the hydrolysis of galactolipids, which are
      the main lipids present in vegetable food.

PMID- 15450179
TI  - Two-dimensional crystallization of herpes simplex virus type 1 single-stranded
      DNA-binding protein, ICP8, on a lipid monolayer.
AB  - Herpes simplex virus type 1 single-stranded DNA-binding protein (ICP8) has been
      crystallized on a positively charged lipid monolayer. The crystals belong to the
      planar group p2 with a=39 nm, b=23.2 nm and gamma=87.2 degrees. The projected map
      of ICP8 crystals calculated at a resolution of 3.9 nm shows four ICP8 monomers
      per unit cell with the crystals formed by a parallel arrangement of 16.2 nm
      helical ICP8 filaments. This novel filamentous form has not been reported before.
      The ICP8 monomers show different appearances in projection, suggesting that they
      may adopt different orientations, probably reflecting the strong intermolecular
      and lipid-filament interactions in the crystal. When the 23 nm diameter filaments
      formed by ICP8 in solution at low temperature in the presence of magnesium were
      generated and then layered on the phospholipid monolayer, highly ordered arrays
      of an 8.5 nm filament with a shallow 31.2 nm pitch were observed and
      reconstruction revealed a double-helical structure.

PMID- 15450180
TI  - Chondroitin sulfate proteoglycans of bovine cornea: structural characterization
      and assessment for the adherence of Plasmodium falciparum-infected erythrocytes.
AB  - The structures of the bovine corneal chondroitin sulfate (CS) chains and the
      nature of core proteins to which these chains are attached have not been studied
      in detail. In this study, we show that structurally diverse CS chains are present
      in bovine cornea and that they are mainly linked to decorin core protein. DEAE
      Sephacel chromatography fractionated the corneal chondroitin sulfate
      proteoglycans (CSPGs) into three distinct fractions, CSPG-I, CSPG-II, and CSPG
      III. These CSPGs markedly differ in their CS and dermatan sulfate (DS) contents,
      and in particular the CS structure-the overall sulfate content and 4- to 6
      sulfate ratio. In general, the CS chains of the corneal CSPGs have low to
      moderate levels (15-64%) of sulfated disaccharides and 0-30% DS content.
      Structural analysis indicated that the DS disaccharide units in the CS chains are
      segregated as large blocks. We have also assessed the suitability of the corneal
      CSPGs as an alternative to placental CSPG or the widely used bovine tracheal
      chondroitin sulfate A (CSA) for studying the structural interactions involved in
      the adherence of Plasmodium falciparum-infected red blood cells (IRBCs) to
      chondroitin 4-sulfate. The data demonstrate that the corneal CSPGs efficiently
      bind IRBCs, and that the binding strength is either comparable or significantly
      higher than the placental CSPG. In contrast, the IRBC binding strength of bovine
      tracheal CSA is markedly lower than the human placental and bovine corneal CSPGs.
      Thus, our data demonstrate that the bovine corneal CSPG but not tracheal CSA is
      suitable for studying structural interactions involved in IRBC-C4S binding.

PMID- 15450181
TI  - The inhibition specificity of recombinant Penicillium funiculosum xylanase B
      towards wheat proteinaceous inhibitors.
AB  - The filamentous fungus Penicillium funiculosum produces a mixture of modular and
      non-modular xylanases belonging to different glycoside hydrolase (GH) families.
      In the present study, we heterologously expressed the cDNA encoding GH11 xylanase
      B (XYNB) and studied the enzymatic properties of the recombinant enzyme.
      Expression in Escherichia coli led to the partial purification of a glutathione
      fusion protein from the soluble fraction whereas the recombinant protein produced
      in Pichia pastoris was successfully purified using a one-step chromatography.
      Despite O-glycosylation heterogeneity, the purified enzyme efficiently degraded
      low viscosity xylan [K(m)=40+/-3 g l(-1), V(max)=16.1+/-0.8 micromol xylose min(
      1) and k(cat)=5405+/-150 s(-1) at pH 4.2 and 45 degrees C] and medium viscosity
      xylan [K(m)=34.5+/-3.2 g l(-1), V(max)=14.9+/-1.0 micromol xylose min(
      1)k(cat)=4966+/-333 s(-1) at pH 4.2 and 45 degrees C]. XYNB was further tested
      for its ability to interact with wheat xylanase inhibitors. The xylanase activity
      of XYNB produced in P. pastoris was strongly inhibited by both XIP-I and TAXI-I
      in a competitive manner, with a K(i) of 89.7+/-8.5 and 2.9+/-0.3 nM,
      respectively, whereas no inhibition was detected with TAXI-II. Physical
      interaction of both TAXI-I and XIP-I with XYNB was observed using titration
      curves across a pH range 3-9.

PMID- 15450182
TI  - Vinorine synthase from Rauvolfia: the first example of crystallization and
      preliminary X-ray diffraction analysis of an enzyme of the BAHD superfamily.
AB  - Crystals of vinorine synthase (VS) from medicinal plant Rauvolfia serpentina
      expressed in Escherichia coli have been obtained by the hanging-drop technique at
      305 K with ammonium sulfate and PEG 400 as precipitants. The enzyme is involved
      in the biosynthesis of the antiarrhythmic drug ajmaline and is a member of the
      BAHD superfamily of acyltransferases. So far, no three-dimensional structure of a
      member of this enzyme family is known. The crystals belong to the space group
      P2(1)2(1)2(1) with cell dimensions of a=82.3 A, b=89.6 A and c=136.2 A. Under
      cryoconditions (120 K), a complete data set up to 2.8 A was collected at a
      synchrotron source.

PMID- 15450183
TI  - Cryptococcus neoformans capsule biosynthesis and regulation.
AB  - The capsule is certainly the most prominent virulence factor in Cryptococcus
      neoformans: acapsular strains are avirulent, and capsular polysaccharides have a
      deleterious effect on the immune system. Until very recently, very few genes
      involved in capsule biosynthesis had been identified - and this despite the
      existence of a detailed body of work concerning the capsule's composition,
      structure and their regulation by environmental factors. The tremendous
      development of experimental tools and techniques suited to the study of C.
      neoformans biology together with the sequencing of three complete genomes have,
      over the last three years, enabled the identification of a number of proteins
      which participate directly in biosynthesis of the capsule or which regulate its
      size. Even though this knowledge is still preliminary, it gives us a clearer
      picture of the various events needed for biosynthesis of this fascinating
      structure.

PMID- 15450184
TI  - Role of reserve carbohydrates in the growth dynamics of Saccharomyces cerevisiae.
AB  - The purpose of this study was to explore the role of glycogen and trehalose in
      the ability of Saccharomyces cerevisiae to respond to a sudden rise of the carbon
      flux. To this end, aerobic glucose-limited continuous cultures were challenged
      with a sudden increase of the dilution rate from 0.05 to 0.15 h(-1). Under this
      condition, a rapid mobilization of glycogen and trehalose was observed which
      coincided with a transient burst of budding and a decrease of cell biomass.
      Experiments carried out with mutants defective in storage carbohydrates indicated
      a predominant role of glycogen in the adaptation to this perturbation. However,
      the real importance of trehalose in this response was veiled by the unexpected
      phenotypes harboured by the tps1 mutant, chosen for its inability to synthesize
      trehalose. First, the biomass yield of this mutant was 25% lower than that of the
      isogenic wild-type strain at dilution rate of 0.05 h(-1), and this difference was
      annulled when cultures were run at a higher dilution rate of 0.15 h(-1). Second,
      the tps1 mutant was more effective to sustain the dilution rate shift-up,
      apparently because it had a faster glycolytic rate and an apparent higher
      capacity to consume glucose with oxidative phosphorylation than the wild type.
      Consequently, a tps1gsy1gsy2 mutant was able to adapt to the dilution rate shift
      up after a long delay, likely because the detrimental effects from the absence of
      glycogen was compensated for by the tps1 mutation. Third, a glg1Deltaglg2Delta
      strain, defective in glycogen synthesis because of the lack of the glycogen
      initiation protein, recovered glycogen accumulation upon further deletion of
      TPS1. This recovery, however, required glycogen synthase. Finally, we
      demonstrated that the rapid breakdown of reserve carbohydrates triggered by the
      shift-up is merely due to changes in the concentrations of hexose-6-phosphate and
      UDPglucose, which are the main metabolic effectors of the rate-limiting enzymes
      of glycogen and trehalose pathways.

PMID- 15450185
TI  - Hansenula polymorpha Tup1p is important for peroxisome degradation.
AB  - In the yeast Hansenula polymorpha peroxisomes are selectively degraded upon a
      shift of cells from methanol to glucose-containing media. We identified the H.
      polymorpha TUP1 gene by functional complementation of the peroxisome degradation
      deficient mutant pdd2-4. Tup1 proteins function in transcriptional repression of
      specific sets of genes involved in various cellular processes. Our combined data
      indicate that H. polymorpha TUP1 is involved in regulation of the switch between
      peroxisome biogenesis and selective degradation. The initial DNA fragment that
      complemented H. polymorpha pdd2-4 contained a second gene, encoding H. polymorpha
      Vps4p. Deletion of the VPS4 gene did not affect selective peroxisome degradation.

PMID- 15450186
TI  - Co-expression of a mammalian accessory trafficking protein enables functional
      expression of the rat MCT1 monocarboxylate transporter in Saccharomyces
      cerevisiae.
AB  - We have developed a new heterologous expression system for monocarboxylate
      transporters. The system is based on a Saccharomyces cerevisiae pyk1 mae1 jen1
      triple-deletion strain that is auxotrophic for pyruvate and deficient in
      monocarboxylate uptake. Growth of the yeast cells on ethanol medium supplemented
      with pyruvate or lactate was dependent on the expression of a suitable
      monocarboxylate transporter. We have used the system to characterize the
      functional significance of interactions between the rat MCT1 transporter and its
      ancillary protein CD147. CD147 was shown to improve trafficking of MCT1 to the
      plasma membrane and its uptake activity. Our results demonstrate a new strategy
      for the production of properly folded and correctly targeted membrane proteins in
      a microbial expression system by co-expression of appropriate accessory proteins.

PMID- 15450187
TI  - Different action of killer toxins K1 and K2 on the plasma membrane and the cell
      wall of Saccharomyces cerevisiae.
AB  - Study of Saccharomyces cerevisiae killer toxin-sensitive strains with the
      deltakre2 phenotype (resistant to toxin K1, sensitive to toxin K2) showed that
      the phenotype is complemented by the KRE2 gene not only in intact cells but also
      in spheroplasts, and resistance to K1 thus resides very probably in the plasma
      membrane. deltakre1 deletant displays a faulty interaction with both K1 and K2
      toxin. Hence, Kre1p probably serves as plasma membrane receptor for both toxins.
      Deletants in seven other genes (GDA1, SAC1, LUV1, KRE23, SAC2, KRE21, ERG4)
      exhibit different degrees of the deltakre2-like resistance pattern, but the
      phenotype in deltagda1 and deltasac1 is not connected with a defect in K1 toxin
      interaction with the plasma membrane, similarly as in deltakre6 and deltakre11
      strains with a higher resistance to K2 toxin. Differences between the K1 and K2
      killer toxin thus occur on the level of both the plasma membrane and the cell
      wall.

PMID- 15450188
TI  - DER7, encoding alpha-glucosidase I is essential for degradation of malfolded
      glycoproteins of the endoplasmic reticulum.
AB  - Proteins entering the endoplasmic reticulum (ER) have to acquire an export
      competent structure before they are delivered to their final destination. This
      folding process is monitored by an ER protein quality control system. Folding
      incompetent conformers are eliminated via a mechanism called ER-associated
      protein degradation (ERAD). Genetic studies in the yeast Saccharomyces cerevisiae
      have revealed that carbohydrate modification plays a crucial role in these
      processes. Here we show that a previously isolated der mutant (der7-1) is
      defective in ERAD. We identify DER7 as the gene encoding N-glycan-processing
      alpha-glucosidase I (EC 3.2.1.106) of the ER and demonstrate that its inactivity,
      due to a substitution of the conserved glycine residue at position 725 by
      arginine (G725R) in the der7-1 mutant, leads to ER-stress.

PMID- 15450189
TI  - Arsenical resistance genes in Saccharomyces douglasii and other yeast species
      undergo rapid evolution involving genomic rearrangements and duplications.
AB  - We have isolated and characterized three adjacent Saccharomyces douglasii genes
      that share remarkable structural homology (97% amino acid sequence identity) with
      Saccharomyces cerevisiae ARR1 (ACR1), ARR2 (ACR2) and ARR3 (ACR3) genes involved
      in arsenical resistance. The ARR2 and ARR3 genes encoding the cytoplasmic
      arsenate reductase and the plasma membrane arsenite transporter are functionally
      interchangeable in both yeast species. In contrast, a single copy of S. douglasii
      ARR1 gene is not sufficient to complement the arsenic hypersensitivity of a S.
      cerevisiae mutant lacking the transcriptional activator Arr1p. This inability may
      be related to a deletion of a 35-bp sequence including the putative Yap-binding
      element in the ARR1 promoter of S. douglasii. Different mechanisms of regulation
      of ARR1 genes expression may therefore explain the increased tolerance of S.
      douglasii to arsenic in comparison with S. cerevisiae. The apparent duplication
      of the ARR gene cluster in the S. douglasii genome may constitute another factor
      contributing to the observed differences in arsenic sensitivity. Comparison of
      ARR genes from the genomes of several yeast species indicates that they are
      located in subtelomeric regions undergoing rapid evolution involving large-scale
      genomic rearrangements.

PMID- 15450190
TI  - Disruption of the MNN10 gene enhances protein secretion in Kluyveromyces lactis
      and Saccharomyces cerevisiae.
AB  - Screening for genes affecting super-secreting phenotype of the over-secreting
      mutant of Kluyveromyces lactis resulted in isolation of the gene named KlMNN10,
      sharing high homology with Saccharomyces cerevisiae MNN10. The disruption of the
      KlMNN10 in Kluyveromyces lactis, as well as of MNN10 and MNN11 in Saccharomyces
      cerevisiae, conferred the super-secreting phenotype. MNN10 isolated from
      Saccharomyces cerevisiae suppressed the super-secretion phenotype in
      Kluyveromyces lactis klmnn10, as did the homologous KlMNN10. The genes MNN10 and
      MNN11 of Saccharomyces cerevisiae encode mannosyltransferases responsible for the
      majority of the alpha-1,6-polymerizing activity of the mannosyltransferase
      complex. These data agree with the view that the structure of glycoproteins in a
      yeast cell wall strongly influences the release of homologous and heterologous
      proteins in the medium. The set of genes namely the suppressors of the over
      secreting phenotype, could be attractive for further analysis of gene functions,
      over-secreting mechanisms and for construction of new strains optimized for
      heterologous protein secretion. KlMNN10 has EMBL accession no. AJ575132.

PMID- 15450191
TI  - Directional ligation of long-flanking homology regions to selection cassettes for
      efficient targeted gene-disruption in Candida albicans.
AB  - PCR-product directed gene disruption with a marker cassette having short homology
      regions is often used in Candida albicans. However, it is quite inefficient due
      to the high frequency of non-homologous recombination at non-targeted loci, which
      necessitates extensive screening to identify the correct disruptants. Thus, many
      PCR-based methods to introduce long flanking homology regions have been developed
      to increase the frequency of integration at the targeted loci. However, these
      methods are not that amenable for use with the widely employed C. albicans marker
      cassettes having direct repeats, as these repeats tend to recombine during PCR,
      resulting in shorter amplified products without the selection marker. To
      circumvent this limitation, we have developed a dinucleotide-sticky-end-ligation
      strategy to add one flanking homology region to one side of the selection
      cassette, and the other flanking homology region to the other side of the
      selection cassette. This method involves release of the selection cassette from
      the plasmid by digestion with two different restriction enzymes, followed by
      partial fill-in, to provide a unique two base overhang at each end of the
      cassette. The flanking homology regions, corresponding to the gene to be
      disrupted, are individually PCR-amplified, and treated with T4-DNA Polymerase in
      the presence of appropriate dNTPs to yield two base-5' overhangs. The primers
      used for the PCR have additional bases at the 5' ends such that after T4 DNA
      Polymerase treatment, the two flanks will have distinct overhangs compatible with
      the overhangs of the partially filled-in selection cassette. The selection
      cassette and the flanks are then ligated together and directly used to transform
      C. albicans. We have successfully used this method for disruption of several C.
      albicans genes. We have also used this method to recreate insertion mutations
      obtained with transposons to reconfirm the mutant phenotypes. This approach can
      be extended to other organisms like Schizosaccharomyces pombe which also require
      long flanking regions of homology for targeted gene disruption.

PMID- 15450192
TI  - Botryozyma mucatilis sp. nov., an anamorphic ascomycetous yeast associated with
      nematodes in poplar slime flux.
AB  - A new species of Botryozyma, Botryozyma mucatilis, was isolated from the surface
      of free-living nematodes, Panagrellus dubius, inhabiting slime flux from hybrid
      poplars, Populus deltoidesxtrichocarpa, in Oregon, USA. This species was
      discovered in relatively close proximity to the teleomorphic species
      Ascobotryozyma americana and Ascobotryozyma cognata, both collected from P.
      dubius nematodes inhabiting beetle galleries in Populus spp. and Populus and
      Salix spp., respectively. B. mucatilis is recognized as a distinct species based
      on molecular and morphological data. Sequence divergence in both the D1/D2 domain
      of the nuclear large-subunit rDNA and internal transcribed spacer region rDNA,
      low DNA reassociation values, notably different amplified fragment-length
      polymorphic fingerprints, and significantly longer cells all support the
      designation of a novel species.

PMID- 15450193
TI  - Rhodotorula cycloclastica sp. nov., Rhodotorula retinophila sp. nov., and
      Rhodotorula terpenoidalis sp. nov., three limonene-utilizing yeasts isolated from
      soil.
AB  - During a search for yeasts that hydroxylate monoterpenes, four yeast strains were
      isolated from soil and plant residue in monoterpene-rich environments using
      enrichment techniques with cyclohexanedioic acid or cyclohexanedimethanol as sole
      carbon source. These strains were able to utilize (+)-limonene supplied as a
      vapor as only carbon source. The yeasts have a CoQ-10 system. Morphology and
      physiological properties of the strains did not fit any known yeast species.
      Recent analysis of the 26S D1/D2 and ITS-5.8S rDNA sequences of basidiomycetous
      yeasts showed that these strains represented three hitherto unknown species of
      Rhodotorula and fell in a cluster consisting of Rhodotorula philyla and the
      mycoparasitic fungus Colacogloea peniophorae. Descriptions of three new species
      Rhodotorula cycloclastica (type strain TVN 309=UOFS Y 2046=CBS 8448), Rhodotorula
      retinophila (type strain TVN 295=UOFS Y 2043=CBS 8446), Rhodotorula terpenoidalis
      (type strain TVN 310=UOFS Y 2042=CBS 8445) are proposed to accommodate these
      isolates.

PMID- 15450195
TI  - Proceedings and abstracts of the 6th International Meeting on Microbial
      Epidemiological Markers. Les Diablerets, Switzerland, 27-30 August 2003.

PMID- 15450194
TI  - Application and evaluation of denaturing gradient gel electrophoresis to analyse
      the yeast ecology of wine grapes.
AB  - The performance of denaturing gradient gel electrophoresis (DGGE) for analysing
      yeasts associated with wine grapes was compared with cultural isolation on malt
      extract agar (MEA). After optimisation of PCR and electrophoretic conditions, the
      lower limit of yeast detection by PCR-DGGE was 10(2) cfuml(-1), although this
      value was affected by culture age and the relative populations of the species in
      mixed culture. In mixed yeast populations, PCR-DGGE detected species present at
      10-100-fold less than other species but not when the ratio exceeded 100-fold.
      Aureobasidium pullulans was the main species isolated from immature, mature, and
      both damaged and undamaged grapes. It was not detected by PCR-DGGE when present
      at populations less than 10(3) cfug(-1). When approaching maturity, damaged
      grapes gave a predominance of Metschnikowia and Hanseniaspora species (10(5)
      10(7) cfug(-1)), all detectable using PCR-DGGE. However, various species of
      Rhodotorula, Rhodosporidium and Cryptococcus were not detected by this method,
      even when populations were as high as 10(4) cfug(-1). PCR -DGGE was less
      sensitive than culture on MEA for determining the yeast ecology of grapes and
      could not reliably detect species present at populations less than 10(4) cfug(
      1). However, this method detected a greater diversity of species than agar
      plating.

PMID- 15450196
TI  - Population structure and evolutionary origins of Microsporum canis, M.
      ferrugineum and M. audouinii.
AB  - The recurrent evolutionary emergence of asexual lineages within sexual zoo- and
      anthropophilic dermatophyte species living in animal-frequented soil is likely to
      be triggered by changes in ecological niche, i.e., shifts of host animal.
      Subsequent adaptation to the new host species is noted. Sometimes geographic
      isolation or intrinsic host factors like human race may also play a role in
      speciation. In the present study, we elaborate concepts of speciation in
      dermatophytes using the Microsporum canis complex as an example. The group
      consists of a cluster of phylogenetically closely related anamorphs: the
      anthropophilic taxa Microsporum audouinii and M. ferrugineum, and the zoophilic
      taxon M. canis. The sexually reproducing species underlying this complex is
      Arthroderma otae. The study is done by an analysis of the population structure of
      about 200 isolates and using intergenic spacers, non-translated regions of genes
      as well as hypervariable microsatellite markers that are known to evolve at high
      mutation rates. The results suggest that sympatric speciation took place already
      during the period where mating ability was maintained and thus that strictly
      clonal fungal species emerged in Africa and led to genetically isolated clonal
      species elsewhere.

PMID- 15450197
TI  - International dissemination of antibiotic resistant strains of bacterial
      pathogens.
AB  - The increasing incidence of methicillin and multiple resistant Staphylococcus
      aureus (MRSA) in nosocomial infections is mainly associated with a wide,
      international dissemination of well defined clonal lineages (epidemic MRSA) which
      are clearly different from community acquired MRSA by molecular typing patterns
      and structure of the staphylococcal cassette chromosome containing the mecA gene.
      Although belonging to a definite subpopulation within the species Enterococcus
      faecium, hospital associated vancomycin resistant isolates also containing the
      esp gene have very likely evolved by acquisition of glycopeptide resistance gene
      clusters at different occasions and at different times by a susceptible already
      disseminated clonal lineage. There is obviously a continuous selection of new
      types of extended spectrum beta-lactamases in enterobacteriaceae and also
      horizontal spread of bla-genes. Intrahospital dissemination of particular strains
      has often been observed, however, an international dissemination until now has
      been described only for Salmonella enterica serovar Typhimurium producing the CTX
      M-3 enzyme. Multiresistant isolates of Salmonella enterica serovar Typhimurium
      phage type DT104 harbour a multiresistant gene cluster with resistance genes from
      taxonomically more unrelated species (tetG, floR, bla(PSE1)). Although in vitro
      transduction has been demonstrated, this gene cluster has only rarely been
      reported from isolates exhibiting other phage patterns of the same serovar or
      from other serovars of S. enterica.

PMID- 15450198
TI  - The use of molecular typing for epidemiological surveillance and investigation of
      endemic nosocomial infections.
AB  - While molecular typing methods are widely used to help the epidemiologist in the
      investigation of outbreaks, their use for the investigation of endemic infections
      has been limited. For the investigation of a micro-epidemiological setting such
      as the understanding of endemic nosocomial infections, discriminant methods are
      needed, such as pulsed field gel electrophoresis (PFGE), or PCR related typing
      methods. However, for long-term surveillance, preference should be given to
      typing methods that give definite results. The identification of the source or
      reservoir is only possible with comprehensive screening of the environment and
      the endogenous flora of patients and staff, and therefore, requires significant
      resources. However, cross-contamination or the existence of a common exogenous
      source might be investigated by typing clinical isolates during non-epidemic
      periods. Cross-contamination is suspected when isolates from different patients
      belong to the same type and when an epidemiological relation can be established.
      Thus, molecular typing makes it possible to track the dissemination of specific
      clones, it may facilitate the breaking down of endemic transmission to the level
      of micro-epidemics. This is illustrated by the example of one investigation of
      Pseudomonas aeruginosa colonization/infection in patients hospitalized in
      intensive care units.

PMID- 15450199
TI  - The development of a typing method for an uncultivable microorganism: the example
      of Pneumocystis jirovecii.
AB  - The development of a molecular typing method for the uncultivable fungus
      Pneumocystis jirovecii is described. The method consists of the amplification by
      PCR of four variable regions of P. jirovecii genome, followed by the detection of
      the polymorphisms by the single-strand conformation polymorphism technique. About
      70% of the patients harbored two or rarely three alleles of at least one of the
      four genomic regions. This was shown to most probably be due to co-infections
      with several P. jirovecii types. Each combination of four alleles of the four
      genomic regions defines a type. Analysis of the alleles and their abundance
      allows identification of the co-infecting types in about 65% of the specimens co
      infected with two types. The method has been validated by the evaluation of
      several criteria. The main advantage of the method is that it is relatively cheap
      and that up to 50 specimens can be analysed at the same time. Its main
      disadvantage is that about 30% of the specimens cannot be typed because of the
      complexity of the alleles configuration. This multitarget typing method has been
      used for several epidemiological purposes.

PMID- 15450200
TI  - Anthrax molecular epidemiology and forensics: using the appropriate marker for
      different evolutionary scales.
AB  - Precise identification of Bacillus anthracis isolates has aided forensic and
      epidemiological analyses of natural anthrax cases, bioterrorism acts and
      industrial scale accidents by state-sponsored bioweapons programs. Because there
      is little molecular variation among B. anthracis isolates, identifying and using
      rare variation is crucial for precise strain identification. We think that
      mutation is the primary diversifying force in a clonal, recently emerged
      pathogen, such as B. anthracis, since mutation rate is correlated with diversity
      on a per locus basis. While single nucleotide polymorphisms (SNPs) are rare,
      their detection is facilitated by whole genome discovery approaches. As highly
      stable phylogenetic markers, SNPs are useful for identifying long branches or key
      phylogenetic positions. Selection of single, diagnostic "Canonical SNPs"
      (canSNPs) for these phylogenetic positions allows for efficient and defining
      assays. We have taken a nested hierarchal strategy for subtyping B. anthracis,
      which is consistent with traditional diagnostics and applicable to a wide range
      of pathogens. Progressive hierarchical resolving assays using nucleic acids
      (PHRANA) uses a progression of diagnostic genomic loci that are initially highly
      stable but with low resolution and, ultimately, very unstable but with high
      resolution. This approach mitigates the need for data weighting and provides both
      a deeply rooted phylogenetic hypothesis and high resolution discrimination among
      closely related isolates.

PMID- 15450201
TI  - The molecular epidemiology of mumps virus.
AB  - The molecular epidemiology of MuV is characterized by the co-existence of 10 (or
      more) distinct genotypes named A-J based on the nucleotide sequence of the SH
      gene. MuV show distinct geographic clustering. More than one genotype may
      circulate simultaneously in a geographic region. Limited data suggest
      redistribution of genotypes to occur over time. The selective forces remain
      speculative. Currently used vaccine strains belong to different genotypes. Some
      MuV genotypes (C, D, H, J) and vaccine strains (Urabe Am9) have been associated
      with enhanced neurovirulence. Also, reduced cross-neutralization capacity has
      been observed between genotype A and genotypes C and D. At present vaccine
      failure cannot be attributed to this phenomenon. Strain redistribution may lead
      to the emergence of new MuV strains with enhanced neurovirulence or reduced cross
      neutralization capacity with current vaccine strains. Close monitoring of the
      genotype distribution of MuV and genotype-specific population immunity is needed
      in the vaccine era.

PMID- 15450202
TI  - Compilation of a MALDI-TOF mass spectral database for the rapid screening and
      characterisation of bacteria implicated in human infectious diseases.
AB  - A database of MALDI-TOF mass spectrometry (MS) profiles has been developed with
      the aim of establishing a high throughput system for the characterisation of
      microbes. Several parameters likely to affect the reproducibility of the mass
      spectrum of a taxon were exhaustively studied. These included such criteria as
      sample preparation, growth phase, culture conditions, sample storage, mass range
      of ions, reproducibility between instruments and the methodology prior to
      database entry. Replicates of 12 spectra per sample were analysed using a 96-well
      target plate containing central wells for peptide standards to correct against
      mass drift during analysis. The quality of the data was assessed statistically
      prior to database addition using root mean squared values of <3.0 as the
      criterion for rejection. Cluster analysis using a nearest neighbour algorithm
      also enabled subsets of data to be compared. This was achieved using the bespoke
      MicrobeLynx trade mark software. Columbia blood agar was used to standardise all
      procedures for the database, since it permitted the culture of most human
      pathogens and also produced spectra with a broad range of mass ions. In some
      instances, alternative media such as CLED were used in specific studies with
      greater success. Following standardisation of the procedure, a database was
      developed comprising ca. 3500 spectra with multiple strain entries for most
      species. The results to date show unequivocally that as the number of strains per
      species increased, so too did the success of species matching. The technique
      demonstrated unique mass spectral profiles for each genus/species, with the
      variation in mass ions among strains/species being dependent on the intra
      specific diversity. The success of identification against the database for wild
      type strains ranged between 33 and 100%; the lower percentage results being
      generally associated with poor representation of some species within the
      database. These findings provide a new dimension for the rapid and high
      throughput characterisation of human pathogens with potentially broad
      applications across the field of microbiology.

PMID- 15450203
TI  - Multilocus sequence typing of Candida albicans: strategies, data exchange and
      applications.
AB  - Multilocus sequence typing of Candida albicans: strategies, data exchange and
      applications. Bougnoux, M.-E., Aanensen, D.M., Morand, S., Theraud, M., Spratt,
      B.G., and d'Enfert, C. Infection, Genetics and Evolution. C. albicans is a
      commensal of humans and animals but is also the main fungal pathogen of humans,
      ranking fourth among the microorganisms responsible for hospital-acquired
      bloodstream infections. Information on the genetic diversity and dynamics of the
      C. albicans population and on the characteristics of C. albicans strains causing
      invasive infections in immunocompromised patients is important in order to adapt
      prevention policies. Important results in this field have been obtained using the
      Ca3 fingerprinting probe. Recently, multilocus sequence typing (MLST) based on
      the sequencing of 6-8 selected house-keeping genes and identification of
      polymorphic nucleotide sites has been introduced for the characterization of C.
      albicans isolates. Combination of the alleles at the different loci results in
      unique diploid sequence types (DSTs) that can be used to discriminate strains.
      MLST has now been successfully applied to study the epidemiology of C. albicans
      in the hospital as well as the diversity of C. albicans isolates obtained from
      diverse ecological niches including human and animal hosts. Furthermore, MLST
      data for C. albicans are available in a public database
      (http://calbicans.mlst.net) that provides a new resource to evaluate the
      worldwide diversity of C. albicans and the relationships of isolates identified
      at various locations.

PMID- 15450204
TI  - Inhibitory effect of lysophosphatidylcholine on pancreatic lipase-mediated
      hydrolysis in lipid emulsion.
AB  - In the lipid metabolism pathway, dietary lipid emulsified with bile salts and
      phospholipids is mainly digested by pancreatic lipase into free fatty acids and
      monoacylglycerols. In order to study substrate recognition mechanism of a
      pancreatic lipase, we investigated its catalytic property toward the lipid
      emulsion prepared with long- or intermediate-chain acylglycerols and several
      physiological surfactants. When lysophosphatidylcholine (LysoPC), rather than
      bile salts or phospholipid, was incorporated into the lipid emulsion, it caused
      an increase in the Km(app) and a decrease in the Vmax(app) values in the
      interactions between the lipase and triacylglycerol (triolein or tricaprin). This
      indicated that LysoPC inhibited hydrolysis by decreasing both the substrate
      affinities and the catalytic activity of this lipase. Interestingly, further
      addition of taurodeoxycholic acid sodium salts or phospholipid completely
      restored the inhibitory effect of LysoPC on hydrolysis by lipase. On the other
      hand, the change in these kinetic values between the lipase and two 1
      monoacylglycerols (1-monocaprin and 1-monoolein) were not particularly large when
      LysoPC was added. Particle size analysis of the lipid emulsion composed of LysoPC
      and triacylglycerols showed that most of the particles were less than 200 nm in
      size, which was smaller than the particle size in the triacylglycerol emulsions
      containing bile salts or phospholipid. The composition of the emulsion would
      affect its surface characteristics and thus contribute to changing lipase
      activity.

PMID- 15450205
TI  - Defective VLDL metabolism and severe atherosclerosis in mice expressing human
      apolipoprotein E isoforms but lacking the LDL receptor.
AB  - Differences in affinity of human apolipoprotein E (apoE) isoforms for the low
      density lipoprotein receptor (LDLR) are thought to result in the differences in
      lipid metabolism observed in humans with different APOE genotypes. Mice
      expressing three common human apoE isoforms, E2, E3, and E4, in place of
      endogenous mouse apoE were used to investigate the relative roles of apoE
      isoforms in LDLR- and non-LDLR-mediated very low density lipoprotein (VLDL)
      clearance. While both VLDL particles isolated from mice expressing apoE3 and
      apoE4 bound to mouse LDLR with affinity and Bmax similar to VLDL containing mouse
      apoE, VLDL with apoE2 bound with only half the Bmax. In the absence of the LDLR,
      all lines of mice expressing human apoE showed dramatic increases in VLDL
      cholesterol and triglycerides (TG) compared to LDLR knockout mice expressing
      mouse apoE. The mechanism of the hyperlipidemia in mice expressing human apoE
      isoforms is due to impairment of non-LDL-receptor-mediated VLDL clearance. This
      results in the severe atherosclerosis observed in mice expressing human apoE but
      lacking the LDLR, even when fed normal chow diet. Our data show that defects in
      LDLR independent pathway(s) are a potential factor that trigger
      hyperlipoproteinemia when the LDLR pathway is perturbed, as in E2/2 mice.

PMID- 15450206
TI  - Lysophospholipid regulates release and activation of latent TGF-beta1 from
      chondrocyte extracellular matrix.
AB  - Transforming growth factor beta-1 (TGF-beta1) is released from the extracellular
      matrix of rat growth plate chondrocytes and activated by stromelysin-1 (matrix
      metalloproteinase 3, MMP-3), an enzyme that is stored in matrix vesicles. MMP-3
      is released from these extracellular organelles by the direct action of
      1alpha,25(OH)2D3 via activation of phospholipase A2 (PLA2), resulting in local
      production of lysophospholipids and matrix vesicle membrane destabilization. This
      effect of 1alpha,25(OH)2D3 is greater in matrix vesicles from growth zone
      chondrocyte cultures and PLA2 activity is higher in the growth zone in vivo,
      suggesting that it may depend on chondrocyte maturation state in the endochondral
      lineage. Previous studies have shown that latent TGF-beta1 can be activated by
      mild detergents in vitro, suggesting that lysophospholipids may act in vivo in a
      similar manner. To test this hypothesis, we determined if rat costochondral
      growth plate cartilage cells produce lysophosphatidylcholine (LPC) and
      lysophosphatidylethanolamine (LPE) in a maturation state-dependent manner and if
      LPC or LPE could release and activate latent TGF-beta1 from the extracellular
      matrix produced by these cells. Rat growth plate chondrocytes produced both
      lysophospholipids, with growth zone cells producing higher levels of LPE via
      PLA1, and resting zone cells producing higher levels of LPC via PLA2. LPC and LPE
      directly increased activation of recombinant human latent TGF-beta1 in a biphasic
      manner with a peak at 2 microg/ml. Phosphatidylcholine, phosphatidylethanolamine,
      and LPE plasmalogen (LPEP), but not choline, also activated TGF-beta1. Latent TGF
      beta1 incubated with LPC or LPE, but neither lysophospholipid alone, stimulated
      [3H]-thymidine incorporation of resting zone cells, indicating the TGF-beta1
      released was biologically active. LPC and LPE also released TGF-beta1 in a dose-
      and time-dependent manner when incubated with cell-free extracellular matrices
      produced by the cells. These results indicate that LPC and LPE have important
      roles as regulators of rat growth plate chondrocytes by directly and indirectly
      activating TGF-beta1 stored in the extracellular matrix.

PMID- 15450207
TI  - Regulation of group VIA phospholipase A2 expression by sterol availability.
AB  - Several lines of evidence suggest that glycerophospholipid mass is maintained
      through the coordinate regulation of CTP:phosphocholine cytidylyltransferase
      alpha (CTalpha) and the group VIA calcium-independent phospholipase A2 (iPLA2).
      CTalpha expression is modulated by sterol and this is mediated in part through
      sterol regulatory element binding proteins (SREBP). In this report, we
      investigate the possibility that iPLA2 expression is controlled in a similar
      manner. When Chinese hamster ovary (CHO) cells were cultured under sterol
      depleted conditions, iPLA2 catalytic activity, mRNA, and protein were induced by
      between two- and threefold. These inductions were suppressed when the cells were
      supplemented with exogenous sterols. Luciferase reporter assays indicated that
      sterol depletion induced transcription of iPLA2, an analysis of the 5' flanking
      region suggested that the iPLA2 gene contained a putative sterol regulatory
      element (SRE), and electrophoretic mobility shift assay (EMSA) analysis indicated
      that this element can bind SREBP-2. Notably, a mutant CHO cell line (SRD4) that
      constitutively generates mature SREBP proteins exhibited increased iPLA2 activity
      and expression compared to wild-type cells. These data suggest that iPLA2
      expression is regulated in a manner consistent with other important genes in
      sterol and glycerophospholipid metabolism. Such coordinate regulation may be
      essential for maintaining the lipid composition of cell membranes.

PMID- 15450208
TI  - Highly polymorphic repeat region in the CETP promoter induces unusual DNA
      structure.
AB  - Genetic variation in the human cholesteryl ester transfer protein (CETP) promoter
      is associated with HDL cholesterol levels and cardiovascular disease with much of
      the genetic variation in CETP attributed to the promoter region. In this region,
      there are several single nucleotide polymorphisms as well as a variable length
      tandem repeat located 1946 base pairs upstream of the CETP transcription start
      that is highly polymorphic with respect to both length and sequence. There are
      more than 10 different long alleles and these vary in their repeat structure. We
      find that the short allele of this repeat is associated with high HDL cholesterol
      levels in vivo (P<0.0001). In males, this association is independent of the
      nearby -629 polymorphism. In addition, the variable length GAAA repeat can
      stimulate an adjacent GGGGA repeat to form a structure that hinders DNA
      amplification and sequencing. This structure also has an effect in vivo as shown
      by orientation effects and cloning efficiency in Escherichia coli.

PMID- 15450209
TI  - The involvement of cytosolic lipases in converting phosphatidyl choline to
      substrate for galactolipid synthesis in the chloroplast envelope.
AB  - Here we report that cytosolic phospholipases are involved in the utilization of
      phosphatidylcholine (PC) as substrate for chloroplast-localized synthesis of
      monogalactosyldiacylglycerol (MGDG). Isolated chloroplasts were pre-incubated
      with lysoPC and [14C]18:0-CoA to form [14C]PC. When soluble plant proteins
      (cytosol) and UDP-galactose were added, [14C] MGDG was formed. An inhibitor of
      phospholipase D markedly lowered the formation of [14C]MGDG, whereas thermolysin
      pretreatment of the chloroplasts was without effect. The cytosolic activity
      resided in the >100-kDa fraction. In a second approach, [14C]PC-containing lipid
      mixtures were incubated with cytosol. Degradation of [14C]PC to
      [14C]diacylglycerol was highest when the lipid composition of the mixture
      mimicked that of the outer chloroplast envelope. We also investigated whether PC
      of extraplastidic origin could function as substrate for MGDG synthesis. Isolated
      chloroplasts were incubated with enriched endoplasmic reticulum containing
      radiolabelled acyl lipids. In the presence of cytosol and UDP-galactose, there
      was a time-dependent transfer of [14C]PC from this fraction to chloroplasts,
      where [14C]MGDG was formed. We conclude that chloroplasts recruit cytosolic
      phospholipase D and phosphatidic acid phosphatase to convert PC to
      diacylglycerol. Apparently, these lipases do not interact with chloroplast
      surface proteins, but rather with outer membrane lipids, either for association
      to the envelope or for substrate presentation.

PMID- 15450210
TI  - Glucose and fatty acid metabolism in McA-RH7777 hepatoma cells vs. rat primary
      hepatocytes: responsiveness to nutrient availability.
AB  - The overabundance of dietary fats and simple carbohydrates contributes
      significantly to obesity and metabolic disorders associated with obesity. The
      liver balances glucose and lipid distribution, and disruption of this balance
      plays a key role in these metabolic syndromes. We investigated (1) how
      hepatocytes balance glucose and fatty acid metabolism when one or both nutrients
      are supplied in abundance and (2) whether rat hepatoma cells (McA-RH7777) reflect
      nutrient partitioning in a similar manner as compared with primary hepatocytes.
      Increasing media palmitate concentration increased fatty acid uptake,
      triglyceride synthesis and beta-oxidation. However, hepatoma cells had a 2-fold
      higher fatty acid uptake and a 2-fold lower fatty acid oxidation as compared with
      primary hepatocytes. McA-RH7777 cells did not synthesize significant amounts of
      glycogen and preferentially metabolized the glucose into lipids or into
      oxidation. In primary hepatocytes, the glucose was mostly spared from oxidation
      and instead partitioned into both de novo glycogen and lipid synthesis. Overall,
      lipid production was rapidly induced in response to either glucose or fatty acid
      excess and this may be one of the earliest indicators of metabolic syndrome
      development associated with nutrient excess.

PMID- 15450212
TI  - Extracting branching tubular object geometry via cores.
AB  - Blood vessels and other anatomic objects in the human body can be described as
      trees of branching tubes. The focus of this paper is the extraction of the
      branching geometry in three-dimensional, as well as the extraction of the tubes
      themselves, via skeletons computed as cores. Cores are height ridges of a graded
      measure of medial strength called medialness, which measures how much a given
      location resembles the middle of an object as indicated by image intensities.
      Object bifurcations are detected using an affine-invariant corner detector and
      computations on the core's medialness values. The methods presented in this paper
      are evaluated on synthetic images of branching tubular objects as well as on
      blood vessels in head MR angiogram data. Results show impressive resistance to
      noise and the ability to detect branches spanning a variety of widths and
      branching angles. An extension that allows cores to extract general branching
      structures, not only branching tubes, is introduced.

PMID- 15450213
TI  - Integrating watersheds and critical point analysis for object detection in
      discrete 2D images.
AB  - This paper presents an improved method for the detection of "significant" low
      level objects in medical images. The method overcomes topological problems where
      multiple redundant saddle points are detected in digital images. Information
      derived from watershed regions is used to select and refine saddle points in the
      discrete domain and to construct the watersheds and watercourses (ridges and
      valleys). We also demonstrate an improved method of pruning the tessellation by
      which to define low level objects in zero order images. The algorithm was applied
      on a set of medical images with promising results. Evaluation was based on
      theoretical analysis and human observer experiments.

PMID- 15450214
TI  - Brain morphometry using 3D moment invariants.
AB  - This paper advocates the use of shape descriptors based on moments of 3D
      coordinates for morphometry of the cortical sulci. These descriptors, which have
      been introduced more than a decade ago, are invariant relatively to rotations,
      translations and scale and can be computed for any topology. A rapid insight into
      the derivation of these invariants is proposed first. Then, their potential to
      characterize shapes is shown from a principal component analysis of the 12 first
      invariants computed for 12 different deep brain structures manually drawn for 7
      different brains. Finally, these invariants are used to find some correlates of
      handedness and sex among the shapes of 116 different cortical sulci automatically
      identified in each of 142 brains of the ICBM database.

PMID- 15450215
TI  - Boundary and medial shape analysis of the hippocampus in schizophrenia.
AB  - Statistical shape analysis has become of increasing interest to the neuroimaging
      community due to its potential to precisely locate morphological changes and thus
      potentially discriminate between healthy and pathological structures. This paper
      describes a combined boundary and medial shape analysis based on two different
      shape descriptions applied to a study of the hippocampus shape abnormalities in
      schizophrenia. The first shape description is the sampled boundary implied by the
      spherical harmonic SPHARM description. The second one is the medial shape
      description called M-rep. Both descriptions are sampled descriptions with
      inherent point correspondence. Their shape analysis is based on computing
      differences from an average template structure analyzed using standard group mean
      difference tests. The results of the global and local shape analysis in the
      presented hippocampus study exhibit the same patterns for the boundary and the
      medial analysis. The results strongly suggest that the normalized hippocampal
      shape of the schizophrenic group is different from the control group, most
      significantly as a deformation difference in the tail region.

PMID- 15450216
TI  - Automatic segmentation of different-sized white matter lesions by voxel
      probability estimation.
AB  - A new method for fully automated segmentation of white matter lesions (WMLs) on
      cranial MR imaging is presented. The algorithm uses five types of regular MRI
      scans. It is based on a K-Nearest Neighbor (KNN) classification technique, which
      builds a feature space from voxel intensity features and spatial information. The
      technique generates images representing the probability per voxel being part of a
      WML. By application of thresholds on these probability maps binary segmentations
      can be produced. ROC-curves show that the segmentations achieve a high
      sensitivity and specificity. Three similarity measures, the similarity index
      (SI), the overlap fraction (OF) and the extra fraction (EF), are calculated for
      evaluation of the results and determination of the optimal threshold on the
      probability map. Investigation of the relation between the total lesion volume
      and the similarity measures shows that the method performs well for lesions
      larger than 2 cc. The maximum SI per patient is correlated to the total WML
      volume. No significant relation between the lesion volume and the optimal
      threshold has been observed. The probabilistic equivalents of the SI, OF en EF
      (PSI, POF and PEF) allow direct evaluation of the probability maps, which
      provides a strong tool for comparison of different classification results. A
      significant correlation between the lesion volume and the PSI and the PEF has
      been noticed. This method for automated WML segmentation is applicable to lesions
      of different sizes and shapes, and reaches an accuracy that is comparable to
      existing methods for multiple sclerosis lesion segmentation. Furthermore, it is
      suitable for detection of WMLs in large and longitudinal population studies.

PMID- 15450217
TI  - GIST: an interactive, GPU-based level set segmentation tool for 3D medical
      images.
AB  - While level sets have demonstrated a great potential for 3D medical image
      segmentation, their usefulness has been limited by two problems. First, 3D level
      sets are relatively slow to compute. Second, their formulation usually entails
      several free parameters which can be very difficult to correctly tune for
      specific applications. The second problem is compounded by the first. This paper
      describes a new tool for 3D segmentation that addresses these problems by
      computing level-set surface models at interactive rates. This tool employs two
      important, novel technologies. First is the mapping of a 3D level-set solver onto
      a commodity graphics card (GPU). This mapping relies on a novel mechanism for GPU
      memory management. The interactive rates level-set PDE solver give the user
      immediate feedback on the parameter settings, and thus users can tune free
      parameters and control the shape of the model in real time. The second technology
      is the use of intensity-based speed functions, which allow a user to quickly and
      intuitively specify the behavior of the deformable model. We have found that the
      combination of these interactive tools enables users to produce good, reliable
      segmentations. To support this observation, this paper presents qualitative
      results from several different datasets as well as a quantitative evaluation from
      a study of brain tumor segmentations.

PMID- 15450218
TI  - Region segmentation using information divergence measures.
AB  - Image segmentations based on maximum likelihood or maximum a posteriori analyses
      of object textures usually assume parametric models (e.g., Gaussian) for
      distributions of these features. For real images, parameter accuracy and model
      stationarity may be elusive, so that model-free inference methods ought to have
      an advantage over those that are model-dependent. Functions of the relative
      entropy (RE) from information theory can produce minimum error, model-free
      inferences, and can detect the boundary of an image object by maximizing the RE
      between the pixel distributions inside and outside a flexible curve contour. A
      generalization of the RE -- the Jensen-Renyi divergence (JRD) -- computes optimal
      n-way decisions and can contour multiple objects in an image simultaneously. Seed
      regions expand naturally and multiple contours tend not to overlap. An edge
      detector based on the JRD, combined with multivariate pixel segmentation,
      generally improved the error of the segmentation. We apply these functions to
      contour patient anatomy in X-ray computed tomography for radiotherapy treatment
      planning.

PMID- 15450219
TI  - Automated segmentation of the left ventricle in cardiac MRI.
AB  - We present a fully automated deformable model technique for myocardium
      segmentation in 3D MRI. Loss of signal due to blood flow, partial volume effects
      and significant variation of surface grey value appearance make this a difficult
      problem. We integrate various sources of prior knowledge learned from annotated
      image data into a deformable model. Inter-individual shape variation is
      represented by a statistical point distribution model, and the spatial
      relationship of the epi- and endocardium is modeled by adapting two coupled
      triangular surface meshes. To robustly accommodate variation of grey value
      appearance around the myocardiac surface, a prior parametric spatially varying
      feature model is established by classification of grey value surface profiles.
      Quantitative validation of 121 3D MRI datasets in end-diastolic (end-systolic)
      phase demonstrates accuracy and robustness, with 2.45 mm (2.84 mm) mean deviation
      from manual segmentation.

PMID- 15450220
TI  - Segmentation of 4D cardiac MR images using a probabilistic atlas and the EM
      algorithm.
AB  - In this paper an automatic atlas-based segmentation algorithm for 4D cardiac MR
      images is proposed. The algorithm is based on the 4D extension of the expectation
      maximisation (EM) algorithm. The EM algorithm uses a 4D probabilistic cardiac
      atlas to estimate the initial model parameters and to integrate a priori
      information into the classification process. The probabilistic cardiac atlas has
      been constructed from the manual segmentations of 3D cardiac image sequences of
      14 healthy volunteers. It provides space and time-varying probability maps for
      the left and right ventricles, the myocardium, and background structures such as
      the liver, stomach, lungs and skin. In addition to using the probabilistic
      cardiac atlas as a priori information, the segmentation algorithm incorporates
      spatial and temporal contextual information by using 4D Markov Random Fields.
      After the classification, the largest connected component of each structure is
      extracted using a global connectivity filter which improves the results
      significantly, especially for the myocardium. Validation against manual
      segmentations and computation of the correlation between manual and automatic
      segmentation on 249 3D volumes were calculated. We used the 'leave one out' test
      where the image set to be segmented was not used in the construction of its
      corresponding atlas. Results show that the procedure can successfully segment the
      left ventricle (LV) (r = 0.96), myocardium (r = 0.92) and right ventricle (r =
      0.92). In addition, 4D images from 10 patients with hypertrophic cardiomyopathy
      were also manually and automatically segmented yielding a good correlation in the
      volumes of the LV (r = 0.93) and myocardium (0.94) when the atlas constructed
      with volunteers is blurred.

PMID- 15450221
TI  - A statistically based flow for image segmentation.
AB  - In this paper we present a new algorithm for 3D medical image segmentation. The
      algorithm is versatile, fast, relatively simple to implement, and semi-automatic.
      It is based on minimizing a global energy defined from a learned non-parametric
      estimation of the statistics of the region to be segmented. Implementation
      details are discussed and source code is freely available as part of the 3D
      Slicer project. In addition, a new unified set of validation metrics is proposed.
      Results on artificial and real MRI images show that the algorithm performs well
      on large brain structures both in terms of accuracy and robustness to noise.

PMID- 15450222
TI  - A brain tumor segmentation framework based on outlier detection.
AB  - This paper describes a framework for automatic brain tumor segmentation from MR
      images. The detection of edema is done simultaneously with tumor segmentation, as
      the knowledge of the extent of edema is important for diagnosis, planning, and
      treatment. Whereas many other tumor segmentation methods rely on the intensity
      enhancement produced by the gadolinium contrast agent in the T1-weighted image,
      the method proposed here does not require contrast enhanced image channels. The
      only required input for the segmentation procedure is the T2 MR image channel,
      but it can make use of any additional non-enhanced image channels for improved
      tissue segmentation. The segmentation framework is composed of three stages.
      First, we detect abnormal regions using a registered brain atlas as a model for
      healthy brains. We then make use of the robust estimates of the location and
      dispersion of the normal brain tissue intensity clusters to determine the
      intensity properties of the different tissue types. In the second stage, we
      determine from the T2 image intensities whether edema appears together with tumor
      in the abnormal regions. Finally, we apply geometric and spatial constraints to
      the detected tumor and edema regions. The segmentation procedure has been applied
      to three real datasets, representing different tumor shapes, locations, sizes,
      image intensities, and enhancement.

PMID- 15450223
TI  - 3D image segmentation of deformable objects with joint shape-intensity prior
      models using level sets.
AB  - We propose a novel method for 3D image segmentation, where a Bayesian
      formulation, based on joint prior knowledge of the object shape and the image
      gray levels, along with information derived from the input image, is employed.
      Our method is motivated by the observation that the shape of an object and the
      gray level variation in an image have consistent relations that provide
      configurations and context that aid in segmentation. We define a maximum a
      posteriori (MAP) estimation model using the joint prior information of the object
      shape and the image gray levels to realize image segmentation. We introduce a
      representation for the joint density function of the object and the image gray
      level values, and define a joint probability distribution over the variations of
      the object shape and the gray levels contained in a set of training images. By
      estimating the MAP shape of the object, we formulate the shape-intensity model in
      terms of level set functions as opposed to landmark points of the object shape.
      In addition, we evaluate the performance of the level set representation of the
      object shape by comparing it with the point distribution model (PDM). We found
      the algorithm to be robust to noise and able to handle multidimensional data,
      while able to avoid the need for explicit point correspondences during the
      training phase. Results and validation from various experiments on 2D and 3D
      medical images are shown.

PMID- 15450224
TI  - Mapping techniques for aligning sulci across multiple brains.
AB  - Visualization and mapping of function on the cortical surface is difficult
      because of its sulcal and gyral convolutions. Methods to unfold and flatten the
      cortical surface for visualization and measurement have been described in the
      literature. This makes visualization and measurement possible, but comparison
      across multiple subjects is still difficult because of the lack of a standard
      mapping technique. In this paper, we describe two methods that map each
      hemisphere of the cortex to a portion of a sphere in a standard way. To quantify
      how accurately the geometric features of the cortex -- i.e., sulci and gyri --
      are mapped into the same location, sulcal alignment across multiple brains is
      analyzed, and probabilistic maps for different sulcal regions are generated to be
      used in automatic labelling of segmented sulcal regions.

PMID- 15450225
TI  - Tuning and comparing spatial normalization methods.
AB  - Spatial normalization is a key process in cross-sectional studies of brain
      structure and function using MRI, fMRI, PET and other imaging techniques. A wide
      range of 2D surface and 3D image deformation algorithms have been developed, all
      of which involve design choices that are subject to debate. Moreover, most have
      numerical parameters whose value must be specified by the user. This paper
      proposes a principled method for evaluating design choices and choosing parameter
      values. This method can also be used to compare competing spatial normalization
      algorithms. We demonstrate the method through a performance analysis of a
      nonaffine registration algorithm for 3D images and a registration algorithm for
      2D cortical surfaces.

PMID- 15450226
TI  - Grid powered nonlinear image registration with locally adaptive regularization.
AB  - Multi-subject non-rigid registration algorithms using dense deformation fields
      often encounter cases where the transformation to be estimated has a large
      spatial variability. In these cases, linear stationary regularization methods are
      not sufficient. In this paper, we present an algorithm that uses a priori
      information about the nature of imaged objects in order to adapt the
      regularization of the deformations. We also present a robustness improvement that
      gives higher weight to those points in images that contain more information.
      Finally, a fast parallel implementation using networked personal computers is
      presented. In order to improve the usability of the parallel software by a
      clinical user, we have implemented it as a grid service that can be controlled by
      a graphics workstation embedded in the clinical environment. Results on inter
      subject pairs of images show that our method can take into account the large
      variability of most brain structures. The registration time for images of size
      256 x 256 x 124 is 5 min on 15 standard PCs. A comparison of our non-stationary
      visco-elastic smoothing versus solely elastic or fluid regularizations shows that
      our algorithm converges faster towards a more optimal solution in terms of
      accuracy and transformation regularity.

PMID- 15450227
TI  - Accurate assessment of patellar tracking using fiducial and intensity-based
      fluoroscopic techniques.
AB  - Accuracies of a point-based and an intensity-based fluoroscopic methods of
      assessing patella tracking were determined by comparing the pattern of patellar
      motion with respect to orientation (flexion, internal rotation, and lateral tilt)
      and translation (lateral, proximal, and anterior) with the pattern of patellar
      motion measured using Roentgen stereophotogrammetric analysis in three cadaver
      knee specimens. Each pose in the patellar motion could be obtained from single as
      well as multiple calibrated fluoroscopic images. The errors using the intensity
      based method were slightly higher than those of the point-based method, but they
      appear to be sufficiently low to detect clinically significant differences in
      patellar kinematics.

PMID- 15450228
TI  - Statistical shape modeling of low level visual area borders.
AB  - This paper proposes a statistical modeling of functional landmarks delimiting low
      level visual areas which are highly variable across individuals. Low level visual
      areas are first precisely delineated by fMRI retinotopic mapping which provides
      detailed information about the correspondence between the visual field and its
      cortical representation. The model is then built by learning the variability
      within a given training set. It relies on an appropriate data representation and
      on the definition of an intrinsic coordinate system common to all visual maps.
      This allows to build a consistent training set on which a principal component
      analysis is eventually applied. Our approach constitutes a first step toward a
      functional landmark-based probabilistic atlas of low level visual areas.

PMID- 15450229
TI  - Generalized image models and their application as statistical models of images.
AB  - A generalized image model (GIM) is presented. Images are represented as sets of
      four-dimensional (4D) sites combining position and intensity information, as well
      as their associated uncertainty and joint variation. This model seamlessly allows
      for the representation of both images and statistical models (such as those used
      for classification of normal/abnormal anatomy and for inter-patient
      registration), as well as other representations such as landmarks or meshes. A
      GIM-based registration method aimed at the construction and application of
      statistical models of images is proposed. A procedure based on the iterative
      closest point (ICP) algorithm is modified to deal with features other than
      position and to integrate statistical information. Furthermore, we modify the ICP
      framework by using a Kalman filter to efficiently compute the transformation. The
      initialization and update of the statistical model are also described.
      Preliminary results show the feasibility of the approach and its potentialities.

PMID- 15450230
TI  - Statistical shape model of atria, ventricles and epicardium from short- and long
      axis MR images.
AB  - We describe a new 3-D statistical shape model of the heart consisting of atria,
      ventricles and epicardium. The model was constructed by combining information on
      standard short- and long-axis cardiac MR images. In the model, the variability of
      the shape was modeled with PCA- and ICA-based shape models as well as with non
      parametric landmark probability distributions and a probabilistic atlas. The
      statistical atlas was built from 25 healthy subjects. The shape model was
      evaluated by applying it to image segmentation. The probabilistic atlas was found
      to be superior to the other shape models (P < 0.001) in this study.

PMID- 15450231
TI  - Validation of dynamic heart models obtained using non-linear registration for
      virtual reality training, planning, and guidance of minimally invasive cardiac
      surgeries.
AB  - Current minimally invasive techniques for beating heart surgery are associated
      with three major limitations: the shortage of realistic and safe training
      methods, the process of selecting port locations for optimal target coverage from
      X-rays and angiograms, and the sole use of the endoscope for instrument
      navigation in a dynamic and confined 3D environment. To supplement the current
      surgery training, planning and guidance methods, we continue to develop our
      Virtual Cardiac Surgery Planning environment (VCSP) -- a virtual reality, patient
      specific, thoracic cavity model derived from 3D pre-procedural images. In this
      work, we create and validate dynamic models of the heart and its components. A
      static model is first generated by segmenting one of the image frames in a given
      4D data set. The dynamics of this model are then extracted from the remaining
      image frames using a non-linear, intensity-based registration algorithm with a
      choice of six different similarity metrics. The algorithm is validated on an
      artificial CT image set created using an excised porcine heart, on CT images of
      canine subjects, and on MR images of human volunteers. We found that with the
      appropriate choice of similarity metric, our algorithm extracts the motion of the
      epicardial surface in CT images, or of the myocardium, right atrium, right
      ventricle, aorta, left atrium, pulmonary arteries, vena cava and epicardial
      surface in MR images, with a root mean square error in the 1 mm range. These
      results indicate that our method of modeling the motion of the heart is easily
      adaptable and sufficiently accurate to meet the requirements for reliable cardiac
      surgery training, planning, and guidance.

PMID- 15450232
TI  - Molecular genetics: the Emperor's clothes of drug discovery?

PMID- 15450233
TI  - Designer vaccine for Alzheimer's?

PMID- 15450234
TI  - Surprise at genotoxicity findings for childhood leukaemia therapy.

PMID- 15450235
TI  - New generation leukaemia drugs are on their way.

PMID- 15450236
TI  - Hard to swallow!

PMID- 15450237
TI  - Sonophoresis: a 50-year journey.

PMID- 15450238
TI  - Turning from monogamy to strategic promiscuity.

PMID- 15450239
TI  - Medicinal chemistry: new technologies and developments.

PMID- 15450240
TI  - Discovery of novel nuclear receptor modulating ligands: an integral role for
      peptide interaction profiling.
AB  - There is currently a marketed drug for nearly every nuclear receptor for which
      the natural ligand has been identified. However, because of the complexity of
      signal transduction by this class of ligand-regulated transcription factors, few
      of these drugs have been optimized for pharmaceutical effectiveness. Over the
      past several years, structural and biochemical work has shed light on some of the
      ligand-induced features of nuclear receptors that enable them to trigger signal
      transduction cascades. This review will highlight the use of peptide interactions
      to cluster different classes of ligands and to identify novel nuclear receptor
      modulating ligands as potential drug candidates. Phage display and a multiplexed
      peptide interaction assay are two of the technologies that are key to this
      approach. When used as part of a drug discovery platform, this type of
      biochemical characterization can bridge the gap between high-throughput chemical
      synthesis and disease model testing. Furthermore, the development of these
      methodologies is timely because there is a significant medical need for new and
      improved nuclear receptor drugs that retain beneficial effects but do not have
      undesired side effect activities.

PMID- 15450241
TI  - Allosteric modulation of G protein-coupled receptors: perspectives and recent
      developments.
AB  - Allosteric modulation of G protein-coupled receptors has recently been recognized
      as an alternative approach to gain selectivity in drug action. In this overview,
      allosteric modulators that enhance or diminish the effects of (endogenous)
      agonists or antagonists on a variety of G protein-coupled receptors are
      described. Emphasis is placed on the latest developments in this research area,
      including data on the first clinical studies. It appears that all three major
      classes of G protein-coupled receptors (A, B and C) are amenable to allosteric
      modulation by small molecules. This constitutes an attractive and novel means to
      identify new leads in the drug discovery process. However, it requires a re
      engineering of the majority of current assays. Finally, it is suggested to
      introduce the term 'non-competitive agonism' or 'allosteric agonism' next to
      allosteric modulation.

PMID- 15450242
TI  - Oncolytic viruses for the treatment of cancer: current strategies and clinical
      trials.
AB  - Tumor-selective replicating viruses offer appealing advantages over conventional
      cancer therapy and are a promising new approach for the treatment of human
      cancer. The development of virotherapeutics is based on several strategies that
      each provides a different foundation for tumor-selective targeting and
      replication. Results emerging from clinical trials with oncolytic viruses
      demonstrate the safety and feasibility of a virotherapeutic approach and provide
      early indications of efficacy. Strategies to overcome potential obstacles and
      challenges to virotherapy are currently being explored and are discussed here.
      Importantly, the successful development of systemic administration of oncolytic
      viruses will extend the range of tumors that can be treated using this novel
      treatment modality.

PMID- 15450247
TI  - Cancer progression: is inhibin alpha from Venus or Mars?
AB  - The inhibin field has been perplexed by the information that inhibin alpha is a
      tumour suppressor in mice yet is elevated in women with ovarian cancer.
      Furthermore, we have consistently observed a down-regulation or loss of inhibin
      alpha in prostate cancer patient samples and cell lines. However, our latest data
      have prompted us to re-evaluate the role of inhibin alpha in prostate and other
      cancers. Using the analogy of TGF-beta as a springboard for our hypothesis, we
      offer a unifying model whereby the previously conflicting observations in mice,
      men and women can be explained. We propose that initially inhibin alpha is tumour
      suppressive and is expressed in benign and early-stage primary cancers. Tumour
      suppressive inhibin alpha is then silenced as the tumour progresses but is
      reactivated as a pro-metastatic factor in advanced, aggressive cancers.

PMID- 15450248
TI  - Constitutive and inducible expression and regulation of vascular endothelial
      growth factor.
AB  - Vascular endothelial growth factor (VEGF), which was originally discovered as
      vascular permeability factor, is critical to human cancer angiogenesis through
      its potent functions as a stimulator of endothelial cell survival, mitogenesis,
      migration, differentiation and self-assembly, as well as vascular permeability,
      immunosuppression and mobilization of endothelial progenitor cells from the bone
      marrow into the peripheral circulation. Genetic alterations and a chaotic tumor
      microenvironment, such as hypoxia, acidosis, free radicals, and cytokines, are
      clearly attributed to numerous abnormalities in the expression and signaling of
      VEGF and its receptors. These perturbations confer a tremendous survival and
      growth advantage to vascular endothelial cells as manifested by exuberant tumor
      angiogenesis and a consequent malignant phenotype. Understanding the regulatory
      mechanisms of both inducible and constitutive VEGF expression will be crucial in
      designing effective therapeutic strategies targeting VEGF to control tumor growth
      and metastasis. In this review, molecular regulation of VEGF expression in tumor
      cells is discussed.

PMID- 15450249
TI  - Novel neurotrophin-1/B cell-stimulating factor-3 (NNT-1/BSF-3)/cardiotrophin-like
      cytokine (CLC)--a novel gp130 cytokine with pleiotropic functions.
AB  - Novel neurotrophin-1/B-cell stimulating factor-3 (NNT-1/BSF-3) is a new member of
      the gp130 cytokine family. NNT-1/BSF-3 is a second ligand to the tripartite CNTFR
      complex and activates Jak-STAT, MAPK and PI3/Akt signaling pathways in various
      cell systems. So far, the known functions of NNT-1/BSF-3 encompass neurotrophic
      and B cell stimulatory effects, as well as neuroimmunoendocrine modulation of
      corticotroph function. Gene expression of NNT-1/BSF-3 is stimulated by PKA- and
      PKC-dependent pathways. Cellular secretion of NNT-1/BSF-3 requires heteromeric
      complex formation with other factors, e.g. cytokine-like factor-1 (CLF-1) or
      soluble ciliary neurotrophic factor receptor (sCNTFR). This article reviews the
      current knowledge on NNT-1/BSF-3 expression, secretion, receptor interaction,
      signal transduction and physiologic effects of this novel gp130 cytokine. Remark:
      After preparation of this manuscript, another novel gp130 cytokine named
      neuropoietin (NP) has been reported and shown to be a ligand of the CNTFR
      complex.

PMID- 15450250
TI  - Got RIP? Presenilin-dependent intramembrane proteolysis in growth factor receptor
      signaling.
AB  - A number of cell surface growth factor receptors are subject to presenilin
      dependent regulated intramembrane proteolysis (PS-RIP) after ligand binding
      and/or ectodomain cleavage. PS-RIP is mediated by a highly conserved multi
      component membrane-bound protease, termed gamma-secretase, responsible for
      generating Alzheimer's disease (AD)-associated Abeta peptide from its membrane
      bound beta-amyloid precursor protein (APP), as well as for cleaving a number of
      other type-I membrane receptors. PS-RIP is a conserved cellular process by which
      cells transmit signals from one compartment to another, including the liberation
      of membrane-bound transcription factors. Recent studies indicate that PS-RIP also
      mediates the proteolytic inactivation of heteromeric receptor complexes by
      removing the transmembrane domains required for receptor-receptor interaction.
      Thus, PS-RIP appears to regulate diverse cellular pathways either by generating
      soluble effectors from membrane-bound precursors, or by removing the
      transmembrane domain of a membrane-tethered signaling component.

PMID- 15450251
TI  - Ligands working as receptors: reverse signaling by members of the TNF superfamily
      enhance the plasticity of the immune system.
AB  - The inflammatory cytokine tumor necrosis factor (TNF), as well as most other
      ligand members of the TNF superfamily, exist both as classical soluble cytokines,
      but also in the form of type II transmembrane proteins. Both forms possess
      bioactivity, although some effects are distinct. In addition, an increasing body
      of evidence suggests that the membrane integrated ligands can receive signals,
      i.e. act as receptors which can transmit positive and negative feedback signals
      into the ligand bearing cell. Thus, reverse signaling enables a two-way
      communication in cell-to-cell signaling, and it is conceivable that this bi
      directional signal exchange contributes to the plasticity of the ligand-receptor
      systems. Reverse signaling mainly has been observed in the immune system and
      within the TNF superfamily. Its function is only beginning to emerge warranting
      additional investigation, especially when it comes to therapeutic strategies
      involving cytokine modulation. This review provides an update of the literature
      about reverse signaling of transmembrane TNF family members and discusses its
      potential biological and clinical impact.

PMID- 15450252
TI  - The role of IL-12, IL-23 and IFN-gamma in immunity to viruses.
AB  - IL-12, IL-23 and IFN-gamma form a loop and have been thought to play a crucial
      role against infectious viruses, which are the prototype of "intracellular"
      pathogens. In the last 10 years, the generation of knock-out (KO) mice for genes
      that control IL-12/IL-23-dependent IFN-gamma-dependent mediated immunity (STAT1,
      IFN-gammaR1, IFNgammaR2, IL-12p40 and IL-12Rbeta1) and the identification of
      patients with spontaneous germline mutations in these genes has led to a re
      examination of the role of these cytokines in anti-viral immunity. We here review
      viral infections in mice and humans with genetic defects in the IL-12/IL-23-IFN
      gamma axis. A comparison of the phenotypes observed in KO mice and deficient
      patients suggests that the human IL-12/IL-23-IFN-gamma axis plays a redundant
      role in immunity to most viruses, whereas its mouse counterparts play a more
      important role against several viruses.

PMID- 15450253
TI  - Oncostatin M: a pleiotropic cytokine in the central nervous system.
AB  - Oncostatin M (OSM), a member of the interleukin-6 (IL-6) cytokine family, has yet
      to be well studied, especially in the context of the central nervous system
      (CNS). The biological functions of OSM are complex and variable, depending on the
      cellular microenvironment. Inflammatory responses and tumor development are among
      two of the major events that OSM is involved in. Although OSM levels remain low
      in the normal CNS, elevated expression occurs in pathological conditions.
      Therefore, it is crucial to understand the regulation of OSM to control its
      expression and/or its effects. Accumulating data demonstrate that OSM binds to
      specific receptor complexes, then activates two major signaling pathways: Janus
      Kinase-Signal Transducers and Activators of Transcription (JAK-STAT) and Mitogen
      Activated Protein Kinase (MAPK), to regulate downstream events. In this review,
      we focus on the biological functions of OSM, the signaling pathways of OSM in the
      CNS, and OSM involvement in CNS diseases.

PMID- 15450254
TI  - Histamine-cytokine connection in immunity and hematopoiesis.
AB  - A number of recent studies have led to a reappraisal of the functional capacities
      of histamine in immunity and hematopoiesis. This change of perspective was
      provided by the following findings: (1) the evidence for multiple cellular
      sources of histamine, differing from mature basophils and mast cells by their
      ability to newly synthesize and liberate the mediator without prior storage, (2)
      the discovery of a novel histamine receptor (H4R), preferentially expressed on
      hematopoietic and immunocompetent cells, (3) the potential intracellular activity
      of histamine through cytochrome P450 and (4) the demonstration of a histamine
      cytokine cross-talk. Indeed, cytokines not only modulate the degranulation
      process of histamine but also control its neosynthesis by the histamine-forming
      enzyme, histidine decarboxylase (HDC), at transcriptional and post
      transcriptional levels. In turn, histamine intervenes in the intricate cytokine
      network, regulating cytokine production by immune cells through distinct
      receptors signaling distinct biological effects. This type of regulation is
      particularly relevant in the context of TH1/TH2 differentiation, autoimmunity and
      tumor immunotherapy.

PMID- 15450255
TI  - [Hormonal contraception in France].

PMID- 15450256
TI  - [Molecular mechanisms in sex determination: from gene regulation to pathology].
AB  - Testis determination is the complex process by which the bipotential gonad
      becomes a normal testis during embryo development. As a consequence, this process
      leads to sexual differentiation corresponding to the masculinization of both
      genital track and external genitalia. The whole phenomenon is under genetic
      control and is particularly driven by the presence of the Y chromosome and by the
      SRY gene, which acts as the key initiator of the early steps of testis
      determination. However, many other autosomal genes, present in both males and
      females, are expressed during testis formation in a gene activation pathway,
      which is far to be totally elucidated. All these genes act in a dosage-sensitive
      manner by which quantitative gene abnormalities, due to chromosomal deletions,
      duplications or mosaicism, may lead to testis determination failure and sex
      reversal.

PMID- 15450257
TI  - [Enterocele: clinical risk factors and association with others pelvic floor
      disorders (about 544 defecographies)].
AB  - OBJECTIVE: To study, by means of defecography, clinical risk factors of
      enterocele and association with others pelvic floor disorders. PATIENTS AND
      METHODS: Five hundred and forty-four consecutive female patients were
      investigated by colpocystodefecography with contrast medium in the small bowel.
      One hundred and thirty-six women with enterocele were compared to 408 women
      without enterocele. RESULTS: There were no significant differences in age,
      obstetrical history (parity, foetal macrosomia, instrumental extractions or
      perineal tear to delivery) between the two groups. More women with enteroceles
      had histories of hysterectomies (60% versus 24%) or cystopexies (29% versus 13%).
      Others pelvic floor disorders were associated in 91% of enterocele: rectocele
      (25%), cystocele (42%), uterine prolapse (28%), rectal intussusception (52%),
      rectal prolapse (4%) and abnormal perineal descent (30%). Stress urinary
      incontinence was significantly more frequent in women without enterocele.
      DISCUSSION AND CONCLUSIONS: The study has demonstrated that previous hysterectomy
      and cystopexy increased the risk of enterocele formation and that enterocele and
      others pelvic floor disorders are often concomitant. Enterocele may have a
      pessary effect on urinary disorders. Results of colpocystodefecography reinforce
      the notion of pelvic floor local disease.

PMID- 15450258
TI  - [Mechanical resistance of pelvic ligaments used for incontinence or prolapse
      surgery].
AB  - OBJECTIVE: Underline the objective strength of the pelvic ligaments. PATIENTS AND
      METHODS: Twenty nine human female pelvis cadavers, whose storage conditions
      differed, were used in our study. In each cadaver we dissected all the ligaments
      used in pelvic surgery. A subjective clinical evaluation of the ligament
      properties was performed by visual observation as well as by finger palpation.
      Ligaments were classified into three groups in terms of thickness and apparent
      strength following finger palpation, high, doubtful and low apparent quality
      ligaments. Then a suture taking the entire ligament switched the ligaments and a
      force was applied on the vagina axis until tearing. The device used for strength
      measurement during traction was a Samson type force gauge, which was developed
      for the purpose of our study. Results were given in Newtons. RESULTS: We found a
      great variability in the values obtained at tearing with maximal values at 200
      newtons and minimal at 22. Individually measured, ligament strength varied
      between individuals, and for a same patient between the type of ligaments and the
      side. The pre-vertebral ligament was on average the strongest. For bilateral
      ligaments, there was no difference between the left and right side. The
      iliopectineal ligament was statistically significantly stronger than sacrospinous
      and arcus tendineus of pelvic fascia. There was a correlation between subjective
      evaluation and objective strength measurements. DISCUSSION AND CONCLUSION: We
      performed the only study of the strength of pelvic ligaments at tearing. These
      are, however, routinely used in the cure of prolapse and urinary incontinence.
      Our results show that there is a great variability in strength between
      individuals, and for a same patient between the types of ligaments and side.
      These observations could explain some of the surgical intervention failures and
      demonstrate the importance of per-operative strength evaluation. Per-operative
      subjective evaluation on strength is related to objective measurements and could
      be used to determine the type of ligaments to be used for surgical assembly
      suspension.

PMID- 15450259
TI  - [Cesarean section for failed vacuum extraction: risk factors and maternal and
      neonatal outcomes].
AB  - OBJECTIVE: To evaluate risk factors associated with failed attempts of vacuum
      extraction and their outcomes. PATIENTS AND METHODS: All trial vacuum extractions
      (metal Minicup) from 1992 to 2000 in Besancon University Hospital Center were
      retrospectively analysed, namely 2447 cases. Univariate and multivariate analyses
      of failed vacuum extraction risk factors and descriptive analyse of outcomes were
      performed. RESULTS: The rate of failed vacuum extractions was 3.47% (85/2447). A
      multivariate analysis showed the following independent risks factors in failed
      extraction: extraction above pelvic level + 2 (OR = 1.8; CI 95%: 1.1-3), newborn
      weight (OR = 2.9; CI 95%: 1.8-4.9), parity >2 (OR = 0.08; CI 95%: 0.01-0.6). In
      case of failed vacuum extraction, newborns had a significantly higher rate of
      Apgar score <7 at 1 min (P = 0.0002), but not at 5 min. These newborns were most
      regularly admitted in pediatric care units (P = 0.01). CONCLUSION: The failed
      trial attempt vacuum extraction rate stays low. These failed instrumental
      extractions are more common in an extraction above pelvic + 2, a high fetal
      weight and an arrest during the second stage of labor. There is an increased
      adverse neonatal outcome. Clinical fetal weight estimation and diagnosis of
      presentation level in mother pelvis must be performed before vacuum extraction.

PMID- 15450260
TI  - [Acute postpartum anaemia. Clinical practice and interest of intravenous iron].
AB  - OBJECTIVES: Postpartum anaemia is a very frequent pathology concerning from 4% to
      27% of patients. The purpose of this study was to estimate clinical practice in
      front of acute postpartum anaemia and to value a new treatment: intravenous iron.
      PATIENTS AND METHODS: Retrospective study over a period of 2 years (April 2001
      March 2003) realised in the Department of Gynaecology and Obstetrics of Belfort
      Regional Hospital. Two hundred and seventeen patients were included (5% of
      deliveries in the same period) with immediate postpartum period haemoglobin <8
      g/dl. Two groups were individualised according to the availability or not of an
      intravenous iron therapy. Clinical and biologic elements concerning deliveries
      were analysed. RESULTS: Average haemoglobin values, from delivery to 48 h after
      it, were 5.81 g/dl for blood-transfused patients, 6.88 g/dl for intravenous iron
      treated patients and 7.43 g/dl for oral iron treated patients. Fifteen patients
      were transfused during the year before the launch of intravenous iron as a
      possible therapy and only five patients the next year. The benefit of haemoglobin
      values with an intravenous iron therapy was 1.9 g/dl on 7 days and 3.1 g/dl on 14
      days. DISCUSSION AND CONCLUSION: These results suggest a real efficiency of
      intravenous iron therapy for acute postpartum anaemia (haemoglobin values <8
      g/dl) with a good tolerance. Patients with haemoglobin values <7 g/dl treated by
      intravenous iron tend to show that some blood transfusions would be thereby
      avoided even though blood transfusion remains the urgency treatment.

PMID- 15450261
TI  - [Primary choriocarcinoma of the ovary: a case report].
AB  - A case of primary choriocarcinoma of the ovary in a 32-year-old woman, 1 month
      after a voluntary interruption of pregnancy, is reported. A review of the
      literature shows that this tumour is rare and the distinction between a
      gestational and a non-gestational choriocarcinoma is difficult. The distinction
      between these two diagnoses and specific treatment are discussed.

PMID- 15450262
TI  - [The impact of infertility and its treatment on sexual life and marital
      relationships: review of the literature].
AB  - This paper reviews the literature on the psychosocial impact of infertility and
      its treatments by the ART on the marital sexuality, by paying special attention
      to the relationship between gender and the infertility experience. It is
      convenient to divide this literature into articles that explore the sexual life
      of the infertile couples on the one hand, and those focusing on the couple
      relationship - marital satisfaction and marital adjustment-, on the other hand.
      The literature on the infertile couples' sexuality and sexual satisfaction,
      mostly descriptive, presents infertility as a deleterious experience for both
      women and men even if the repercussion differ according to gender, with
      correlative dynamic effects within the couple. The contributions to the
      investigation of the couple relationship, mostly quantitative Anglo-Saxon
      studies, have produced equivocal or contradictory results concerning the
      satisfaction with the relationship, the closeness between the two partners so
      that it is difficult to assume a trend in this field. This situation is largely
      due to the problems of sampling. In this view, future research should perform its
      methodological apparatus to take into account the processual nature of the
      infertility experience, at both levels of couple history and its involvement in
      the ART process.

PMID- 15450263
TI  - [Vaginal virucides against HIV].
AB  - Despite intensive efforts to promote condoms as a means of preventing the spread
      of HIV, the rate at which the epidemic is expanding, highlights the need for
      additional prevention technologies, and in particular methods controlled by
      women. Virucides are anti-infective substances, formulated as gels, foams,
      creams, and suppositories and impregnated sponges, for vaginal application. Women
      will be able to insert them prior to sexual intercourse to protect themselves and
      their partners from infection with HIV. Unlike condoms, the woman will control
      them, and their use can be with or without her partner's consent or even
      knowledge. They will not create a physical barrier to reduce sexual pleasure, and
      it will be possible to apply them considerably in advance of sex so that there is
      no interruption to the natural course of events. Virucides will not necessarily
      be contraceptive; ideally, they will be available in a choice of contraceptive
      and non-contraceptive versions. Virucides are not intended to replace other
      prevention measures such as those based on male and female condoms-or vaccines
      when they become available-but will give people a wider choice of potentially
      life-saving methods of protection. About 60 candidate virucides are in the
      development pipeline, representing many different chemical categories and
      different mechanisms of action against infection. About half a dozen are
      scheduled to enter large-scale clinical trials in the near future. Virucides
      offer the prospect of a low-cost, woman-controlled option for self-administered,
      broad-spectrum protection against multiple HIV strains, other sexually
      transmitted pathogens and unwanted pregnancy.

PMID- 15450264
TI  - [Genetic analysis of the fetus using maternal blood].
AB  - Circulating fetal DNA in maternal plasma and serum was first demonstrated by Lo
      et al. in 1997 and has become a useful tool for prenatal diagnosis less than five
      years later. There is more and more evidence that the trophoblastic cells act as
      the major source of this circulating fetal DNA. Contrary to fetal cells analysis
      in maternal blood which requires isolation and enrichment procedures, fetal DNA
      analysis is relatively easy to perform with the use of real-time PCR. Non
      invasive fetal sex and fetal RHD genotype determination are, to date, the two
      main clinical indications. Those newly offered possibilities have changed the
      management of pregnant women who are carriers for X-linked genetic disorders;
      prenatal diagnosis by choriovillous sampling could only be performed for male
      fetuses avoiding an unnecessary risk of fetal loss for female fetuses. Moreover,
      fetal RHD genotyping by maternal blood analysis could be useful in RhD-negative
      women at risk of immunization in order to adapt prophylactic anti-D injection.

PMID- 15450265
TI  - [Place and results of frozen section analysis in the management of malignant and
      borderline ovarian tumors].
AB  - The management of ovarian tumors discovered during laparoscopy depends equally on
      the surgeon and the pathologist. Thus, the surgeon will undergo a more or less
      radical surgery depending on frozen section analysis (FSA),which depends mainly
      on the pathologist's skills, the histopathologic type and the volume and the
      localization of the tumor. The accuracy of FSA is higher in ovarian cancer than
      in borderline tumor. In patients treated initially with a laparoscopic approach,
      if the FSA demonstrates the presence of an invasive carcinoma, a conversion to
      laparotomy should be performed in order to complete the surgical staging. If the
      FSA demonstrates the presence of a borderline tumor, an exclusive laparoscopic
      approach could be discussed.

PMID- 15450266
TI  - [For or against systematic screening of breast cancer before the age of fifty?].

PMID- 15450267
TI  - [Breast cancer screening is efficient and useful from the age of forty].

PMID- 15450268
TI  - [Systematic screening of breast cancer after fifty: an arbitrary limit?].

PMID- 15450269
TI  - [On the subject of the recommendations for clinical practice: 2003 Standards,
      Options and Recommendations for the medical frontline treatment of patients with
      malignant epithelial ovarian tumors. Update (summary version)].

PMID- 15450270
TI  - [Treatments of sterility and multiple pregnancies in France: analysis and
      recommendations].

PMID- 15450271
TI  - [Methods and limits of conservative treatment for cervical adenocarcinoma:
      analysis of 9 cases and review of the literature].

PMID- 15450272
TI  - [Genital mycoplasma].

PMID- 15450273
TI  - [Epithelial cyst after vaginal mucous membrane procedure: diagnosis and
      management].

PMID- 15450274
TI  - Introduction to atrial fibrillation and heart failure: a mutually noxious
      association.

PMID- 15450275
TI  - Atrial fibrillation and heart failure: natural history and pharmacological
      treatment.
AB  - Atrial fibrillation (AF) is the most common sustained arrhythmia. Congestive
      heart failure (CHF), an increasingly frequent cardiovascular disorder affecting
      millions of people world-wide, has become the most important risk factor of AF in
      developed countries, as a result of ageing populations. Approximately two thirds
      of patients with CHF are >65 years of age and likely to have AF as a coexistent
      complication. Epidemiological surveys and large clinical trials in CHF provide
      strong evidence that AF is a marker of increased mortality. AF may compromise LV
      systolic function and worsen CHF through poor rate control, irregularity of
      ventricular response, and loss of atrial systolic activity. Furthermore, enhanced
      adrenergic stimulation in the setting of CHF facilitates AV conduction and
      promotes the progression of cardiomyopathy, and AF may worsen CHF as a
      consequence of the negative inotropic effects of drugs used to control the heart
      rate of rhythm, or of the proarrhythmic effects of drugs used to maintain sinus
      rhythm. This article reviews the putative mechanisms behind atrial remodelling
      due to long-standing AF, and the role of neuro-hormonal alterations in the atrial
      electrophysiologic and structural changes which facilitate its perpetuation. It
      also reviews and discusses various controlled trials of angiotensin-converting
      enzyme inhibitors and AT-1 receptor blockade in the perspective of AF treatment
      and prevention. Finally the role of specific antiarrhythmic drugs, the respective
      advantages and shortcomings of rate versus rhythm control in patients with AF and
      CHF, and the important issue of chronic anticoagulation are presented in the
      light of time-tested therapies, as well as new promising therapeutic approaches.

PMID- 15450276
TI  - Surgical treatment of atrial fibrillation: a review.
AB  - The optimal treatment of atrial fibrillation (AF) depends upon a proper
      understanding of the electrophysiological basis of its clinical manifestations.
      Whether AF is continuous (persistent) or intermittent (paroxysmal) depends on
      variable underlying electrophysiology and determines the choice of interventional
      treatment. The initiation of intermittent AF requires a "trigger", often, though
      not always, located near the orifices of pulmonary veins. In contrast, continuous
      AF does not need a "trigger" to be re-induced repetitively and does not depend on
      the pulmonary veins or other abnormal automatic foci for its induction or
      perpetuation. Simple pulmonary vein encircling confines the trigger to the
      pulmonary veins and, if expertly performed, will cure the majority of patients
      with intermittent AF. On the other hand, continuous AF requires a Maze procedure
      or variant thereof to eliminate atrial macro-reentry while allowing sinus rhythm
      to activate the entire atrial myocardium and preserve atrial transport function.
      This article reviews the development of the surgical Maze procedure and its
      implications for the treatment of AF by percutaneous intracardiac or epicardial,
      minimally invasive techniques. High-intensity focussed ultrasound, a new energy
      source generating frictional heat, appears promising in the creation of focussed
      transmural lesions, while preserving the integrity of coronary arterial walls.

PMID- 15450277
TI  - Treatment of atrial fibrillation by catheter-based procedures.
AB  - Catheter-based procedures have been developed with a view to reproduce or improve
      upon the excellent results of the Maze procedure in the treatment of atrial
      fibrillation (AF). Linear epicardial lesions created using minimally invasive
      techniques, or endocardial lesions to encircle the pulmonary veins (PV) have been
      associated with restoration of sinus rhythm in high percentages of carefully
      selected patients. The tricuspid-caval isthmus interruption procedure for atrial
      flutter is highly successful and, in patients who have both atrial flutter and
      fibrillation, prevents the development of AF when combined with antiarrhythmic
      agents. Modification of atrioventricular (AV) nodal conduction by eliminating the
      posterior atrial inputs to the AV node is performed to decrease the ventricular
      rate and alleviate symptoms during AF without the need for permanent pacing,
      though may be complicated by inadvertent AV block. AV junctional ablation and
      permanent pacing alleviates cardiac symptoms, improves quality-of-life, and
      reduces the use of health care resources. Its constraints include the inescapable
      need for anticoagulation, loss of AV synchrony, and life-long pacemaker
      dependency. The variety of methods and results among published studies strongly
      emphasises the importance of patient selection, and the relative importance of
      substrate versus trigger. Possible complications of catheter ablation for AF
      include systemic thromboembolism, PV stenosis, pericardial effusion, cardiac
      tamponade, and phrenic nerve paralysis. These remain a matter of concern and
      stimulate research toward the development of less complex procedures.

PMID- 15450278
TI  - Contributions of permanent cardiac pacing in the treatment of atrial
      fibrillation.
AB  - Newer indications for permanent cardiac stimulation include the prevention of
      paroxysmal atrial fibrillation (AF) and cardiac resynchronisation in patients
      suffering from advanced heart failure. Direct comparisons between VVI and DDD or
      AAI pacing showed an advantage conferred by physiological pacing on the risk of
      developing AF during long-term follow-up in patients with sinus node dysfunction,
      AV block, or both. Furthermore, in patients with conventional pacing indications
      and paroxysmal atrial tachyarrhythmias, a high percentage of atrial pacing was
      associated with a lighter AF burden. This article reviews several important
      issues involved in the optimisation of cardiac pacing with a view to prevent
      paroxysmal AF by new, dedicated pacing algorithms. The AF Suppression trade mark
      algorithm significantly reduced the rates of symptomatic paroxysmal AF. This
      algorithm, which confers its benefit by maintaining the atrial pacing rate
      slightly above the spontaneous sinus rate, should be activated in patients with a
      history of atrial tachyarrhythmia. Implanting the lead in the low atrial septum
      seems to reduce further the frequency of tachyarrhythmic events. Future
      indications for this mode of pacing may be extended to patients at high risk of
      new-onset or recurrent AF, such as candidates for cardiac resynchronisation
      therapy or implantable cardioverter/defibrillator recipients.

PMID- 15450279
TI  - Cardiac resynchronization therapy.
AB  - The first case report introducing the concept of cardiac resynchronisation
      therapy (CRT) was published less than 10 years ago, opening the way to the
      development of the first successful non-pharmacological treatment of congestive
      heart failure (CHF). The now routine implantation of CRT systems is applicable to
      multitudes of patients as adjunctive therapy in advanced CHF. This technique has
      transformed the traditional concepts associated with stimulation of the heart,
      and is now applied not only to restore an appropriate heart rate, but also to
      change the process of cardiac mechanical activation. Since it must be integrated
      within a comprehensive and multidisciplinary CHF management program, CRT has
      changed the practice of experts in the field of cardiac pacing. CRT in the
      management of CHF was ultimately validated in 2 randomised trials. MUSTIC, the
      first trial, compared in a single-blind, 3x3 months crossover design active
      versus inactive biventricular stimulation in a group of patients in sinus rhythm
      and another group in atrial fibrillation. Both phases of the trial were completed
      by 48 patients, with significant positive effects conferred by CRT on the
      distance walked in 6 min and on peak oxygen consumption. The number of
      hospitalizations for management of CHF was decreased by 2/3 (P<0.05), and 85% of
      patients preferred the atrio-biventricular over the inactive stimulation mode
      (P<0.001). These results were amply confirmed by the parallel-design MIRACLE
      trial. The current indications for CRT, diagnostic tools to assist in its
      implementation, and limitations of this new therapeutic adjunct are further
      discussed in this review.

PMID- 15450280
TI  - Atrial fibrillation and cardiac resynchronization therapy: the MASCOT study.
AB  - Atrial fibrillation (AF) and congestive heart failure (CHF) share several
      characteristics and often coexist in the same patient. Both are responsible for
      significant morbidity and mortality, are increasing in prevalence, and are major
      sources of health expenditure. The Management of Atrial fibrillation Suppression
      in AF-HF COmorbidity Therapy (MASCOT) study is a European, single-blind,
      prospective, controlled, multicentre, randomized clinical trial designed to
      examine whether adding the AF Suppression Algorithm to cardiac resynchronization
      therapy (CRT) improves the prognosis of patients with CHF. The patients will be
      randomly assigned to a CRT-only group, with the AF Suppression algorithm
      programmed OFF (control group), versus a CRT+AF Suppression group, with the
      algorithm programmed ON (treatment group). The primary study endpoint is
      development of permanent AF, and secondary endpoints are safety of the AF
      Suppression algorithm, and evolution of multiple clinical variables over 24
      months of follow-up. CRT combined with a refined atrial tachyarrhythmia
      prevention pacing algorithm may represent a major advance in the management of AF
      and CHF by electrical stimulation.

PMID- 15450281
TI  - Atrial fibrillation and heart failure.

PMID- 15450282
TI  - Correction of cervicofacial deformities.

PMID- 15450283
TI  - The adjustable vector deep plane midface lift.
AB  - Midface lifting is valuable rejuvenative options for many patients and can
      provide a more youthful and balanced face. This procedure is well suited for the
      oral and maxillofacial surgeon because of familiarity with the intraoral and
      temporal surgical approaches, and it does not require any specialized equipment.
      This procedure has minimal postoperative recovery and a low complication rate.
      The results of this procedure have remained stable in the author's cohort of
      patients approaching 2 years. Contraindications include atrophic or minimal malar
      fat, in which case there is nothing to elevate. The midface lift can be performed
      as an isolated procedure or as part of multiple facial procedures. The astute
      surgeon considers midface rejuvenation in all cosmetic cases.

PMID- 15450284
TI  - Hair deformities.
AB  - To be able to treat the wide spectrum of hair deformities, a surgeon must possess
      a wide spectrum of skills in HRS, cosmetic surgery, and reconstructive surgery.
      Specific education and training in HRS is not a traditional part of formal
      surgical training, although much information is available through several
      national and international organizations. Being sensitive to the unique variables
      associated with HRS increases the chances of achieving a superior functional and
      cosmetic result when treating significant hair deformities.

PMID- 15450285
TI  - Management of forehead and brow deformities.
AB  - The subcutaneous trichophytic forehead browlift allows rejuvenation of the
      forehead with precise, stable brow positioning, excellent visualization, and
      direct treatment of the brow and forehead musculature. This method avoids
      lengthening the forehead and, with meticulous closure, can produce an
      imperceptible scar and natural-appearing hairline.

PMID- 15450286
TI  - Establishing a cosmetic surgery practice: an algorithm to management of the
      cosmetic surgery patient in your practice.
AB  - As oral and maxillofacial surgeons, we have the skills to provide this service at
      an exceptional level. Each of us must obtain the proper training and continually
      update our knowledge in this area so that we can continue to advance the
      specialty of oral and maxillofacial surgery. Our forefathers in the specialty
      paved the way for us, and that is why we have privilege to practice our
      specialty. Providing cosmetic surgery in your practice can be rewarding.

PMID- 15450287
TI  - Management of isolated neck deformity.
AB  - Rejuvenative surgery for isolated neck deformities can be fulfilling procedure
      for patients and surgeons. With precise understanding of the anatomy of the
      anterior neck, proper patient selection, and sound surgical execution, consistent
      and attractive postoperative outcomes can be expected in every case (Figs. 9,
      10).

PMID- 15450288
TI  - Correction of surface deformities: Botox, soft-tissue fillers, lasers and intense
      pulsed light, and radiofrequency.
AB  - The field of cosmetic surgery continues to be rapidly changing and expanding one.
      With the understanding of the changes that take place in aging and contribute to
      photodamaged skin, technologic advances have become more based in science.
      Patients are aware of these changes and are enthusiastically tracking them
      through all media channels. It has has become more important than ever for
      surgeons to stay abreast of this new knowledge.

PMID- 15450290
TI  - Time-resolved imaging of macromolecular processes and interactions.

PMID- 15450291
TI  - Analytical trapping: extraction of time-independent structures from time
      dependent crystallographic data.
AB  - All chemical and biological reactions involve atomic motion, embodied in dynamic
      structural changes. Identifying these changes is the goal of time-resolved
      crystallography. The "raw" output of a time-resolved macromolecular
      crystallography experiment is the time-dependent set of difference electron
      density maps that span the desired time range and display the time-dependent
      changes in density (and underlying structure) as the reaction progresses. The
      goal is to interpret such data in terms of a small number of crystallographically
      refinable, time-independent structures, each associated with a reaction
      intermediate; to establish the pathways and rate coefficients by which the
      intermediates interconvert; and thus to establish a chemical kinetic mechanism.
      We review briefly the various strategies that may be used to achieve this goal
      and concentrate on two promising advances: singular value decomposition and
      cluster analysis. The strategies are illustrated by using data on the photocycle
      of the bacterial blue light photoreceptor, photoactive yellow protein.

PMID- 15450292
TI  - The structural dynamics of myoglobin.
AB  - Conformational fluctuations in proteins were initially invoked to explain the
      observation that diffusion of small ligands through the matrix is a global
      phenomenon. Small globular proteins contain internal cavities that play a role
      not only in matrix dynamics but also in controlling function, tracing a pathway
      for the diffusion of the ligand to and from the active site. This is the main
      point addressed in this Review, which presents pertinent information obtained on
      myoglobin (Mb). Mb, a simple globular heme protein which binds reversibly oxygen
      and other ligands. The bond between the heme Fe(II) and gaseous ligands can be
      photodissociated by a laser pulse, generating a non-equilibrium population of
      protein structures that relaxes on a picosecond to millisecond time range. This
      process is associated with migration of the ligand to internal cavities of the
      protein, which are known to bind xenon. Some of the results obtained by laser
      photolysis, molecular dynamics simulations, and X-ray diffraction of intermediate
      states of wild-type and mutant myoglobins are summarized. The extended relaxation
      of the globin moiety directly observed by Laue crystallography reflects re
      equilibration among conformational substates known to play an essential role in
      controlling protein function.

PMID- 15450293
TI  - Picosecond time-resolved X-ray crystallography: probing protein function in real
      time.
AB  - A detailed mechanistic understanding of how a protein functions requires
      knowledge not only of its static structure, but also how its conformation evolves
      as it executes its function. The recent development of picosecond time-resolved X
      ray crystallography has allowed us to visualize in real time and with atomic
      detail the conformational evolution of a protein. Here, we report the photolysis
      induced structural evolution of wild-type and L29F myoglobin over times ranging
      from 100 ps to 3 micros. The sub-ns structural rearrangements that accompany
      ligand dissociation in wild-type and the mutant form differ dramatically, and
      lead to vastly different ligand migration dynamics. The correlated protein
      displacements provide a structural explanation for the kinetic differences. Our
      observation of functionally important protein motion on the sub-ns time scale was
      made possible by the 150-ps time resolution of the measurement, and demonstrates
      that picosecond dynamics are relevant to protein function. To visualize subtle
      structural changes without modeling, we developed a novel method for rendering
      time-resolved electron density that depicts motion as a color gradient across the
      atom or group of atoms that move. A sequence of these time-resolved images have
      been stitched together into a movie, which allows one to literally "watch" the
      protein as it executes its function.

PMID- 15450294
TI  - Use of negative stain and single-particle image processing to explore dynamic
      properties of flexible macromolecules.
AB  - Flexible macromolecules pose special difficulties for structure determination by
      crystallography or NMR. Progress can be made by electron microscopy, but electron
      cryo-microscopy of unstained, hydrated specimens is limited to larger
      macromolecules because of the inherently low signal-to-noise ratio. For three
      dimensional structure determination, the single particles must be invariant in
      structure. Here, we describe how we have used negative staining and single
      particle image processing techniques to explore the structure and flexibility of
      single molecules of two motor proteins: myosin and dynein. Critical for the
      success of negative staining is a hydrophilic, thin carbon film, because it
      produces a low noise background around each molecule, and stabilises the molecule
      against damage by the stain. The strategy adopted for single-particle image
      processing exploits the flexibility available within the SPIDER software suite.
      We illustrate the benefits of successive rounds of image alignment and
      classification, and the use of whole molecule averages and movies to analyse and
      display both structure and flexibility within the dynein motor.

PMID- 15450295
TI  - Rapid constriction of lipid bilayers by the mechanochemical enzyme dynamin.
AB  - Dynamin, a large GTPase, is located at the necks of clathrin-coated pits where it
      facilitates the release of coated vesicles from the plasma membrane upon GTP
      binding, and hydrolysis. Previously, we have shown by negative stain electron
      microscopy that wild-type dynamin and a dynamin mutant lacking the C-terminal
      proline-rich domain, DeltaPRD, form protein-lipid tubes that constrict and
      vesiculate upon addition of GTP. Here, we show by time-resolved cryo-electron
      microscopy (cryo-EM) that DeltaPRD dynamin in the presence of GTP rapidly
      constricts the underlying lipid bilayer, and then gradually disassembles from the
      lipid. In agreement with the negative stain results, the dynamin tubes constrict
      from 50 to 40 nm, and their helical pitch decreases from approximately 13 to 9.4
      nm. However, in contrast to the previous results, examination by cryo-EM shows
      that the lipid bilayer remains intact and small vesicles or fragments do not form
      upon GTP binding and hydrolysis. Therefore, the vesicle formation seen by
      negative stain may be due to the lack of mobility of the dynamin tubes on the
      grid during the GTP-induced conformational changes. Our results confirm that
      dynamin is a mechanochemical enzyme and suggest that during endocytosis dynamin
      is directly responsible for membrane constriction. In the cell, other proteins
      may enhance the activity of dynamin or the constraints induced by the surrounding
      coated pit and plasma membrane during constriction may cause the final membrane
      fission event.

PMID- 15450296
TI  - Electron tomography of fast frozen, stretched rigor fibers reveals elastic
      distortions in the myosin crossbridges.
AB  - As a first step toward freeze-trapping and 3-D modeling of the very rapid load
      induced structural responses of active myosin heads, we explored the
      conformational range of longer lasting force-dependent changes in rigor
      crossbridges of insect flight muscle (IFM). Rigor IFM fibers were slam-frozen
      after ramp stretch (1000 ms) of 1-2% and freeze-substituted. Tomograms were
      calculated from tilt series of 30 nm longitudinal sections of Araldite-embedded
      fibers. Modified procedures of alignment and correspondence analysis grouped self
      similar crossbridge forms into 16 class averages with 4.5 nm resolution,
      revealing actin protomers and myosin S2 segments of some crossbridges for the
      first time in muscle thin sections. Acto-S1 atomic models manually fitted to
      crossbridge density required a range of lever arm adjustments to match variably
      distorted rigor crossbridges. Some lever arms were unchanged compared with low
      tension rigor, while others were bent and displaced M-ward by up to 4.5 nm. The
      average displacement was 1.6 +/- 1.0 nm. "Map back" images that replaced each
      unaveraged 39 nm crossbridge motif by its class average showed an ordered mix of
      distorted and unaltered crossbridges distributed along the 116 nm repeat that
      reflects differences in rigor myosin head loading even before stretch.

PMID- 15450297
TI  - Dynamics of EF-G interaction with the ribosome explored by classification of a
      heterogeneous cryo-EM dataset.
AB  - A method of supervised classification using two available structure templates was
      applied to investigate the possible heterogeneity existing in a large cryo-EM
      dataset of an Escherichia coli 70S ribosome-EF-G complex. Two subpopulations
      showing the ribosome in distinct conformational states, related by a ratchet-like
      rotation of the 30S subunit with respect to the 50S subunit, were extracted from
      the original dataset. The possible presence of additional intermediate states is
      discussed.

PMID- 15450298
TI  - Molecular dynamics of protein complexes from four-dimensional cryo-electron
      microscopy.
AB  - Cryo-electron microscopy of single particles offers a unique opportunity to
      detect and quantify conformational variation of protein complexes. Different
      conformers may, in principle, be distinguished by classification of individual
      projections in which image differences arising from viewing geometry are
      disentangled from variability in the underlying structures by "multiple particle
      analysis"--MPA. If the various conformers represent dynamically related states of
      the same complex, MPA has the potential to visualize transition states, and
      eventually to yield movies of the dynamic process. Ordering the various
      conformers into a time series is facilitated if cryo-EM data are taken at
      successive times from a system that is known to be developing in time. Virus
      maturation represents a relatively tractable dynamic process because the changes
      are large and irreversible and the rate of the natural process may be
      conveniently slowed in vitro by adjusting the environmental conditions. We
      describe the strategy employed in a recent analysis of herpes simplex virus
      procapsid maturation (Nat. Struct. Biol. 10 (2003) 334-341), compare it with
      previous work on the maturation of bacteriophage HK97 procapsid, and discuss
      various factors that impinge on the feasibility of performing similar
      experimental analyses of molecular dynamics in the general case.

PMID- 15450299
TI  - Global ribosome motions revealed with elastic network model.
AB  - The motions of large systems such as the ribosome are not fully accessible with
      conventional molecular simulations. A coarse-grained, less-than-atomic-detail
      model such as the anisotropic network model (ANM) is a convenient informative
      tool to study the cooperative motions of the ribosome. The motions of the small
      30S subunit, the larger 50S subunit, and the entire 70S assembly of the two
      subunits have been analyzed using ANM. The lowest frequency collective modes
      predicted by ANM show that the 50S subunit and 30S subunit are strongly anti
      correlated in the motion of the 70S assembly. A ratchet-like motion is observed
      that corresponds well to the experimentally reported ratchet motion. Other slow
      modes are also examined because of their potential links to the translocation
      steps in the ribosome. We identify several modes that may facilitate the E-tRNA
      exiting from the assembly. The A-site t-RNA and P-site t-RNA are found to be
      strongly coupled and positively correlated in these slow modes, suggesting that
      the translocations of these two t-RNAs occur simultaneously, while the motions of
      the E-site t-RNA are less correlated, and thus less likely to occur
      simultaneously. Overall the t-RNAs exhibit relatively large deformations.
      Animations of these slow modes of motion can be viewed at.

PMID- 15450300
TI  - Normal mode based flexible fitting of high-resolution structure into low
      resolution experimental data from cryo-EM.
AB  - A new method for the flexible fitting of high-resolution structures into low
      resolution maps of macromolecular complexes from electron microscopy has been
      recently described in applications to simulated electron density maps. This
      method uses a linear combination of low-frequency normal modes in an iterative
      manner to deform the structure optimally to conform to the low-resolution
      electron density map. Gradient-following techniques in the coordinate space of
      collective normal modes are used to optimize the overall correlation coefficient
      between computed and measured electron densities. With this approach, multi-scale
      flexible fitting can be performed using all-atoms or Calpha atoms. In this paper,
      illustrative studies of normal mode based flexible fitting to experimental cryo
      EM maps are presented for three different systems. Large, functionally relevant
      conformational changes for elongation factor G bound to the ribosome, Escherichia
      coli RNA polymerase and cowpea chlorotic mottle virus are elucidated as the
      result of the application of NMFF from high-resolution structures to cryo
      electron microscopy maps.

PMID- 15450301
TI  - Soy glycinin microcapsules by simple coacervation method.
AB  - Encapsulation of a dispersed oil phase (hexadecane) was realized by simple
      coacervation method using soy glycinin as the wall forming material. Suitable
      emulsification and coacervation conditions, that favor the formation of
      microcapsules wall, were identified and investigated. Mild acid (pH 2.0) and heat
      (55 degrees C) treatments of the reaction medium during the emulsification step
      enhanced significantly the deposition of coacervated glycinin around oil
      droplets. A pronounced correlation between glycinin concentration in the
      continuous phase, specific surface of the dispersed phase and the
      microencapsulation efficiency was also observed. Coacervation step study
      concerned the morphology and the stability of microcapsules. Controlled
      initiation of the coacervation, by slow readjustment of the pH, allowed a
      homogeneous precipitation of glycinin around oil droplets as well as the absence
      of aggregation phenomena. Since the morphology of microcapsules was considerably
      affected by a prolonged stirring of the reaction medium, the coacervation and
      reticulation time were optimized in order to preserve the homogeneity of the
      microcapsules size distribution and the microencapsulation efficiency.

PMID- 15450302
TI  - Preparation of glucose-sensitive microcapsules with a porous membrane and
      functional gates.
AB  - A glucose-sensitive microcapsule with a porous membrane and with linear-grafted
      polyacrylic acid (PAAC) chains and covalently bound glucose oxidase (GOD) enzymes
      in the membrane pores acting as functional gates was successfully prepared.
      Polyamide microcapsules with a porous membrane were prepared by interfacial
      polymerization, PAAC chains were grafted into the pores of the microcapsule
      membrane by plasma-graft pore-filling polymerization, and GOD enzymes were
      immobilized onto the PAAC-grafted microcapsules by a carbodiimide method. The
      release rates of model drug solutes from the fabricated microcapsules were
      significantly sensitive to the existence of glucose in the environmental
      solution. In solution, the release rate of either sodium chloride or VB(12)
      molecules from the microcapsules was low but increased dramatically in the
      presence of 0.2mol/L glucose. The prepared PAAC-grafted and GOD-immobilized
      microcapsules showed a reversible glucose-sensitive release characteristic. The
      proposed microcapsules provide a new mode for injection-type self-regulated drug
      delivery systems having the capability of adapting the release rate of drugs such
      as insulin in response to changes in glucose concentration, which is highly
      attractive for diabetes therapy.

PMID- 15450303
TI  - Cyclooxygenase-2 parallels invasive depth and increased MVD in transitional cell
      carcinoma.
AB  - To investigate the relationship between the expression of cyclooxygenase-2 (COX
      2), and invasive depth and angiogenesis in human transitional cell carcinoma
      (TCC), the expression of COX-2 and von Willebrand factor (vWF) was detected in
      paraffin-embedded transitional cell carcinoma specimens from 50 patients with
      histologically confirmed bladder transitional cell carcinoma. Microvessels were
      counted and microvessel density (MVD) was calculated. The correlation between COX
      2 and invasive depth, MVD and invasive depth, COX-2 and MVD were analyzed. COX-2
      expression was significantly related to the invasive depth of tumors; it solely
      expressed in invasive TCC. The ratio of COX-2 positively stained samples in each
      stage correlated to the invasive stages; so did the proportion of COX-2 (+) cells
      in whole tumor cells. Also, MVD increased with the invasive stages of tumors and
      positively correlated to the invasive depth. The COX-2-positive TCC samples were
      highly vascular, their microvessel density was significantly higher than that of
      the COX-2-negative TCC samples. There was a positive correlation between MVD and
      COX-2 (+) cells proportion. Our findings suggested that COX-2 was positively
      correlated with the invasive depth and involved in the process of angiogenesis in
      human transitional cell carcinoma.

PMID- 15450304
TI  - Interactions between phosphatidylcholines and cholesterol in monolayers at the
      air/water interface.
AB  - Mixtures of cholesterol and synthetic phospholipids, differing in saturation of
      phosphatidylcholine (PC) acyl chains, such as distearoyl phosphatidylcholine
      (DSPC), stearoyl-oleoyl phosphatidylcholine (SOPC) and dioleoyl
      phosphatidylcholine (DOPC) have been studied as floating Langmuir monolayers at
      the air/water interface. In order to examine the influence of a polar group,
      distearoyl phosphatidylethanolamine (DSPE) was chosen. The films were spread at
      room temperature on aqueous subphases and characterized by the surface pressure
      area (pi-A) isotherms and compression modulus (C(s)(-1)) values. The interactions
      were examined by analyzing the mean molecular areas and quantified by the excess
      free energy of mixing values. The obtained results indicate that the affinity of
      cholesterol to saturated/unsaturated phosphatidylcholines does not differ
      significantly, and revealed strong influence of the kind of a polar group on the
      cholesterol-phospholipid interactions. On the other hand, the apolar group
      structure was found to modify the stoichiometry of sterol-PC complexes.

PMID- 15450305
TI  - Influences of fatty acid moiety and esterification of polyglycerol fatty acid
      esters on the crystallization of palm mid fraction in oil-in-water emulsion.
AB  - We examined the crystallization of palm mid fraction (PMF) in oil-in-water (O/W)
      emulsion, after adding polyglycerol fatty acid esters (PGFEs). We employed
      ultrasonic velocity measurements and DSC techniques, with special emphases on the
      influences of fatty acid moiety and esterification of PGFE. Twelve types of PGFEs
      were examined as additives. PGFEs have a large hydrophilic moiety composed of 10
      glycerol molecules to which palmitic, stearic and behenic acids were esterified
      as the fatty acid moiety with different degrees of esterification.
      Crystallization temperature (T(c)) of PMF remarkably increased with increasing
      concentrations of the PGFEs as the chain length of the fatty acid moiety
      increased, and the PGFE became more hydrophobic in accordance with increasing
      degree of esterification. We observed that the heterogeneous nucleation of PMF in
      the O/W emulsion was activated at the oil-water interface, where the template
      effect of very hydrophobic long saturated fatty acid chains of the PGFE might
      play the main role of heterogeneous nucleation.

PMID- 15450306
TI  - Detachable immobilization of liposomes on polymer gel particles.
AB  - Immobilization of liposomes on hydrophobized Sephacryl gel and controlled
      detachment of the liposomes from the gel were examined. The gel was chemically
      modified and bore octyl, hexadecyl or cholesteryl moiety via disulfide linkage as
      anchors to liposomal bilayer membrane. Upon interaction with the gel, egg
      phosphatidylcholine liposomes were successfully immobilized onto the gel. The gel
      with cholesteryl moiety showed 1.7 times higher liposome immobilization per
      anchor moiety than the gels with the alkyl moieties. The immobilization of
      liposomes on the gel was stable, and no significant spontaneous detachment of
      phospholipid or leakage of fluorescein isothiocyanate-conjugated dextran
      encapsulated in the immobilized liposomes was observed in 24h. Reductive cleavage
      of the disulfide linkage by dithiothreitol resulted in detachment of the
      liposomes from the gel. The majority of the detached liposomes were found
      encapsulating the dextran derivative, and these liposomes should have kept their
      structural integrity throughout the immobilization and the detachment processes.
      The release of the liposomes was insignificant until the ratio of the
      dithiothreitol to the hydrophobic anchor reached a threshold. The presence of the
      threshold suggests that the immobilization of liposomes should require a certain
      minimum number of the hydrophobic moieties anchored in the liposomal membrane. By
      applying the present immobilization-detachment system, preparation of liposomes
      encapsulating the dextran derivative without using costly gel filtration or
      ultracentrifugation procedure was successfully demonstrated.

PMID- 15450307
TI  - Interaction between erythrocytes and free phospholipids as an emulsifying agent
      in fat emulsions or drug carrier emulsions for intravenous injections.
AB  - Hemolysis caused by the interaction between rabbit erythrocytes and oil-in-water
      emulsions (e.g., fat emulsions or drug carrier emulsions for intravenous
      injections) prepared with various oil concentrations was investigated. In
      emulsions prepared with oil concentrations in the range of 2.5-12.5%, the
      percentage of both hemolysis and free purified egg yolk lecithins (PEL) in the
      water phase of the emulsions decreased with the increased oil concentration and
      became constant above 12.5% oil concentration. The change in free PEL percentage
      in the water phase of the emulsions prepared with various oil concentrations
      showed the same relationship as that of the percentage hemolysis caused by the
      interaction between rabbit erythrocytes and emulsions prepared with various oil
      concentrations. No hemolysis caused by an interaction between rabbit erythrocytes
      and vesicles prepared with PEL at a concentration of 0.012% was observed.
      However, hemolysis levels of 64.2% and 91.1% were observed at PEL concentrations
      of 0.12% and 1.2%, respectively. These results led to the conclusion that
      hemolysis caused by the interaction between erythrocytes and emulsions was due to
      PEL vesicles in the water phase of the emulsions.

PMID- 15450308
TI  - Changes of uPA and uPA-R expression in the cornea after alkali burn.
AB  - PURPOSE: To investigate the expression levels of uPA and uPA-R in corneal repair
      after alkali burn. METHODS: The corneal alkali burn models were established in
      vitro and in vivo, then immunocytochemistry (ICC) of uPA/uPA-R and image analysis
      and statistical evaluation were performed to determine their expression levels
      both in vitro and in vivo. RESULTS: Compared with control group, the expressions
      of uPA and uPA-R after alkali burn had no significant increases till 6h, then
      increased rapidly from 12h to 24h and reached their maxima at 24h. From 24h,
      their expression levels decreased rapidly. In vivo, they rebounded again after
      48h and attained their second peaks at 96h, respectively. After that, their
      expressions decreased again. The uPA-positive reaction mainly distributed in the
      cytoplasm while that of uPA-R mostly distributed on the cellular membrane. Their
      expression changes were similar to each other, both in vivo and in vitro. In
      vivo, uPA and uPA-R expressed and gathered in the basal layer of corneal
      epithelium. CONCLUSIONS: These results suggest that the time phase of 24h after
      wound is the typical stage associating with the expressional maximum of uPA and
      uPA-R both in vivo and in vitro. Furthermore, the results also imply that the
      expression changes of uPA and uPA-R correlate to the wound healing after the
      corneal alkali burn, uPA and uPA-R coordinate with each other to stimulate the
      wound healing.

PMID- 15450309
TI  - Path-dependency of the interaction between coaggregating and between non
      coaggregating oral bacterial pairs--a thermodynamic approach.
AB  - Coaggregation, i.e. specific recognition between bacteria from different species,
      is a well-described phenomenon in the human oral cavity but remains physically
      poorly understood. With our study we aimed at elucidating some aspects of the
      mechanism of the coaggregation between the oral bacteria Streptococcus oralis J22
      and Actinomyces naeslundii 147, in particular with respect to the driving force
      for coaggregation and its pathway-dependency. To that end, the macroscopic
      turbidity of the bacterial suspension, the morphology of the coaggregates,
      binding isotherms and heats of interaction were compared between the above
      mentioned coaggregating bacterial pair and a non-coaggregating pair,
      Streptococcus sanguis PK1889 and A. naeslundii 147. The coaggregating pair forms
      large aggregates, which rapidly sediment from the suspension while the non
      coaggregating pair forms only very small coaggregates that remain homogeneously
      suspended. Coaggregation is further characterized by a high affinity between the
      partner cells that bind to each other in a strong cooperative mode. The
      interactions between both pairs occur under the release of heat and are thus
      enthalpically favorable. More heat is released for the coaggregating than for the
      non-coaggregating pair. Adding the coaggregating bacteria in steps to each other
      leads to saturation of enthalpically favorable binding sites. This is observed
      when the streptococcus is added to the actinomyces as well as when the addition
      is done the other way around. It is concluded that the cooperativity of the
      coaggregation process is based on an increase of entropy. It is furthermore shown
      that the density of the coaggregates as well as the heat effect of formation of
      these coaggregates depend on the number of steps in which the partner cells are
      added to each other. Adding S. oralis J22 in three steps to A. naeslundii 147
      results in the formation of denser coaggregates under the release of less heat,
      as compared to that of addition in one step. These differences point to a larger
      entropy increase when in a step-wise mixing the coaggregating bacteria are
      allowed to form more densely-packed coaggregates.

PMID- 15450310
TI  - Effects of flunitrazepam on the Lalpha-H(II) phase transition of
      phosphatidylethanolamine using merocyanine 540 as a fluorescent indicator.
AB  - Previous studies of our group demonstrated that flunitrazepam is a lipophilic
      drug capable of interacting with membranes through a partition equilibrium
      phenomenon. Its localization at the phospholipid polar head region could explain
      the decrease in the size of dipalmitoylphosphatidylcholine (dpPC) vesicles,
      through a mechanism that involves the increment in the relative volume of this
      region with a subsequent increase in the vesicle's surface curvature. In the
      present work, we investigated if flunitrazepam can affect the L(alpha)-H(II)
      phase transition of phosphatidylethanolamine through a similar mechanism. This
      study was approached by using merocyanine 540, a dye sensitive to the molecular
      packing of membrane lipids. A detailed analysis of merocyanine absorption and
      fluorescence emission and excitation spectra was performed. The results indicated
      that the fluorescence emitted came mainly from the monomeric form of merocyanine
      and that it resulted a good indicator of this phase transition, as was previously
      described. Flunitrazepam did not affect significantly the onset of the phase
      transition but showed a tendency to diminish the dye fluorescence emission
      intensity, which could involve a lower partition of merocyanine in the vesicles.
      Moreover, the results suggest that this drug produced a delay in the completeness
      of the phase transition and a decrement in the cooperativity of this phenomenon.

PMID- 15450311
TI  - Laparoscopy in the pediatric and adolescent population.
AB  - The use of laparoscopy by gynecologists in treating pediatric and adolescent
      patients is a relatively new phenomenon. This article discusses the specialized
      instrumentation necessary for operating on these patients and preoperative
      considerations and generalized techniques unique to this population. Although
      laparoscopy has a myriad of uses, the main focus is on the diagnosis and
      treatment of pelvic pain, adnexal masses, and pelvic inflammatory disease.
      Incidental appendectomy in these patients is also discussed.

PMID- 15450312
TI  - Laparoscopy in the second trimester of pregnancy.
AB  - Advances in laparoscopic surgery have led to the development of methods to
      perform traditionally major abdominal surgery and reduce morbidity using
      minimally invasive surgery techniques. Because a growing number of reports in the
      literature have suggested its safe use, laparoscopy is being performed in
      pregnancy with increasing frequency in many centers. Any surgeon treating
      pregnant patients must have a thorough understanding of the physiology of the
      pregnant patient and risks and benefits of the surgical procedure. This article
      discusses the use of laparoscopy in pregnancy focusing on the physiologic changes
      induced by pregnancy relevant to laparoscopy. Strategies to reduce the risk of
      complications while performing laparoscopy on a pregnant patient are discussed.

PMID- 15450313
TI  - Laparoscopic abdominal cerclage.
AB  - Cervical cerclage is an effective treatment of cervical incompetence. It is
      conventionally done by laparotomy approach. Laparoscopic abdominal cerclage is a
      less invasive technique that could replace the laparotomy technique. Laparoscopic
      abdominal cerclage does not require hospitalization, is associated with less
      pain, and leads to a faster recovery. Laparoscopic abdominal cerclage is equal to
      or may be better than abdominal cerclage by laparotomy.

PMID- 15450314
TI  - Laparoscopic lymphadenectomy and sentinel node biopsy in uterine cancer.
AB  - This article discusses laparoscopic lymphadenectomy and sentinel node biopsy in
      uterine cancer.

PMID- 15450315
TI  - Total laparoscopic hysterectomy and laparoscopic supracervical hysterectomy.
AB  - Laparoscopic hysterectomy was first performed in 1989 and has become one of the
      procedures that may be offered to women with significant gynecologic symptoms.
      This article describes alternatives to hysterectomy, indications for laparoscopic
      hysterectomy, and outcomes and complications of laparoscopic hysterectomy as
      compared with vaginal and abdominal hysterectomy. Surgical technique for both
      total and supracervical hysterectomy are described as well as the learning curve,
      training, and credentialing for these procedures.

PMID- 15450316
TI  - Laparoscopic treatment of urinary incontinence.
AB  - The optimal surgical management of stress incontinence in women remains a
      contentious issue. Retropubic urethropexies such as the Burch procedure are
      regarded as having excellent long-term success rates. The learning curve for
      transvaginal tape procedures is by far shorter and easier than for the
      laparoscopic Burch procedure. Data from the few randomized trials published thus
      far show that both procedures are associated with high success rates and patient
      satisfaction.

PMID- 15450317
TI  - Laparoscopic pelvic floor repair.
AB  - Articles on laparoscopic approach to pelvic floor reconstruction continue to
      proliferate throughout the worldwide literature. Although procedures like
      laparoscopic Burch seem to be fading fast, other procedures like the laparoscopic
      paravaginal repair and sacral colpopexy seem to be more common and visible in the
      literature. This article reviews the pertinent anatomy, surgical procedures, and
      literature concerning the laparoscopic approach to pelvic floor reconstruction.

PMID- 15450318
TI  - Laparoscopic excision of deep endometriosis.
AB  - Deep endometriosis is essentially characterized by the presence of a rectovaginal
      or retrocervical nodule, which is a circumscribed, nodular aggregate of smooth
      muscle, endometrial glands, and, usually, endometrial stroma. The authors suggest
      that the retroperitoneal space should definitely be considered as the origin of
      this retroperitoneal adenomyotic disease. This article reviews the
      classification, the diagnosis, and the surgical treatment of deep endometriosis
      (adenomyotic disease).

PMID- 15450319
TI  - Laparoscopic management of ovarian cysts.
AB  - The role of operative laparoscopy in the management of patients with adnexal
      masses is expanding, offering distinct advantages of lower morbidity, improved
      postoperative recovery, and reduced cost. Although clinical examination and the
      results of preoperative work-up often indicate the benign or malignant nature of
      the cyst, only histology can provide the absolute diagnosis. Advanced operative
      laparoscopy for management of ovarian cysts, when performed by experienced
      endoscopic surgeons, is as safe and effective as open techniques.

PMID- 15450320
TI  - Laparoscopic management of ovarian remnant.
AB  - Ovarian remnant syndrome has become increasingly recognized as a cause of pelvic
      pain after extirpative surgery. Surgical removal of the ovarian remnant is the
      optimal treatment. Laparoscopy is safe and effective in managing ovarian remnant
      syndrome when performed by an experienced laparoscopist.

PMID- 15450321
TI  - Laparoscopic robotic gynecologic surgery.
AB  - The first gynecologic procedure performed with a robot was a tubal anastomosis.
      This was performed in 1998 with the Zeus robot. Over the past several years other
      gynecologic procedures have been performed with other robots. Current robotic
      technology may not be universally applicable to many gynecologists' clinical
      practice. The field of surgical robotics is evolving at an ever increasing pace,
      however, and gynecologists need to participate in its development.

PMID- 15450322
TI  - Laparoscopic fertility preservation.
AB  - Advances in cancer therapy have improved the long-term survival of young patients
      suffering from malignancies. The adverse effects of the treatment, however, are
      sterility and loss of gonadal function especially in females. If preservation of
      fertility in males by sperm freezing is already established, for young women
      undergoing cancer treatment the availability of preserving the gonadal function
      and fertility has just begun. Diseases commonly treated with radiation or
      chemotherapeutic agents in young women are breast cancer, lymphoma, leukemia,
      blood dyscrasia, glomerulonephritis, lupus erythematosus, and rheumatoid
      arthritis.

PMID- 15450323
TI  - The role of laparoscopy in the diagnosis and treatment of conditions associated
      with chronic pelvic pain.
AB  - Laparoscopy is a useful tool for the diagnosis and treatment of conditions
      associated with chronic pelvic pain. In the evaluation of chronic pelvic pain,
      laparoscopic techniques vary from conservative procedures, such as pain mapping,
      excision, and nerve ablation, to more extensive procedures like oophorectomy and
      hysterectomy. Although useful for diagnosis, laparoscopy continues to have a
      controversial role in the treatment of chronic pelvic pain.

PMID- 15450324
TI  - Progress in transvaginal hydrolaparoscopy.
AB  - Reproductive performance is now more than ever determining the choice of
      treatment for each individual couple. The easy access to ART treatments, their
      financial benefits, and the relative high success rate per cycle are at the basis
      of a liberal referral to these treatments without an accurate diagnosis. The easy
      and comprehensive investigation by a transvaginal endoscopy as a first-line
      diagnostic procedure allows for an accurate diagnosis and the choice of the most
      appropriate treatment.

PMID- 15450325
TI  - Office hysteroscopy.
AB  - The indications for hysteroscopic procedures in gynecologic practice are ample
      and clearly charted: hysteroscopy is considered the gold standard not only for
      visualizing the cervical canal and the uterine cavity, but also for treating many
      different kinds of benign pathologies localized to that region. This article
      summarizes the authors' experience with this technique during the last 14 years,
      which have been devoted to improving the procedure by creating new instruments
      and modifying the technique.

PMID- 15450326
TI  - The technique and overview of flexible hysteroscopy.
AB  - Flexible hysteroscopy is a safe, successful, and reliable method of investigation
      for abnormal uterine bleeding. When compared with rigid hysteroscopy flexible
      hysteroscopy is associated with less pain both at introduction of the
      hysteroscope and during the procedure itself especially when the diameter of the
      scope is reduced. This article provides evidence of the benefits of flexible
      hysteroscopy to the health service provider, clinician, and patient. Flexible
      hysteroscopy is acceptable to most women when performed in the outpatient setting
      without analgesia and offers a suitable alternative to rigid hysteroscopy.

PMID- 15450327
TI  - Hysteroscopic myomectomy.
AB  - Hysteroscopic myomectomy is a minimally invasive technique that eliminates the
      need for a laparotomy and is associated with lower morbidity than abdominal
      myomectomy. Its beneficial effects are reflected by the improvement in menstrual
      pattern, fertility rate, and overall patient satisfaction. It is usually
      performed as outpatient surgery but occasionally requires an overnight stay. Most
      patients return to full activity within 48 hours. To exploit the full potentials
      of this procedure, appropriate case selection and surgical expertise are
      essential. It should be considered as first-line conservative surgical therapy
      for the management of symptomatic intracavitary fibroids.

PMID- 15450328
TI  - Hysteroscopic and nonhysteroscopic endometrial ablation.
AB  - Endometrial ablation is defined as the elimination of the endometrium by thermal
      energy or resection. It was introduced in the 1980s as an alternative to
      hysterectomy to those patients with abnormal uterine bleeding and benign
      pathology who are unable or unwilling to tolerate traditional therapies. This
      article explores various endometrial ablation techniques.

PMID- 15450329
TI  - Hysteroscopic tubal sterilization.
AB  - This article provides an overview of the history of hysteroscopic sterilization
      including the current state of the art and future ideals. Unlike laparoscopic
      techniques, sterilization by hysteroscopy can be performed in an outpatient
      setting without general anesthesia. Many attempts have been made to develop a
      safe and effective method, but until recently, without success. The Essure system
      is the first one that seems to be a realistic alternative to laparoscopic
      sterilization, but is irreversible. The search is still on for the optimum method
      of hysteroscopic sterilization.

PMID- 15450330
TI  - Advances in laparoscopy and hysteroscopy techniques.

PMID- 15450331
TI  - An update on the genetics of psoriasis.
AB  - Psoriasis is a complex inflammatory disorder whose pathogenesis is likely to
      require the contribution of several genes and environmental triggers. Despite the
      difficulties posed by the study of multifactorial conditions, significant
      progress has been achieved in relation to the molecular genetic basis of
      psoriasis. It has long been recognized that the major histocompatibility complex
      (MHC) region on chromosome 6p21 harbors the main determinant conferring psoriasis
      susceptibility. The identification of non-MHC susceptibility regions across the
      genome has been hindered by the likely occurrence of genetic heterogeneity.
      Nonetheless, evidence for the assignment of a number of non-MHC loci has been
      achieved through studies, including the collaborative analysis of large patient
      cohorts, and also through the observation of overlap between psoriasis and atopic
      dermatitis susceptibility regions.

PMID- 15450332
TI  - Current concepts in the immunopathogenesis of psoriasis.
AB  - There is much evidence to support the concept that psoriasis is a type 1
      autoimmune disease, primarily mediated by interferon gamma and other inflammatory
      cytokines. There has been renewed interest in the role of components of the
      innate immune system, however,and it may be that overlap between the innate and
      acquired arms of the immune system can better explain immunopathogenesis in
      psoriasis. Relevant cell types, receptors, and immune mediators within these
      traditional boundaries of the immune system are discussed.Finally, pathogenic
      contributions from important psoriatic mouse models and recent genomic data using
      the new gene chip technology are elaborated.

PMID- 15450333
TI  - From laboratory to clinic: rationale for biologic therapy.
AB  - Traditional systemic therapy for psoriasis is limited by either lack of efficacy
      or the long-term side effect profile of the medications used. Newer information
      about the pathophysiology of the disease has led to new perspectives on
      developing novel techniques for attacking psoriasis. This article discusses the
      pathogenesis of psoriasis, looks at the immunologic factors that contribute to
      forming a psoriatic plaque, reviews how novel biologic therapies are made, and
      explores how biologics can target each of these specific parts of the immunologic
      cascade.

PMID- 15450334
TI  - Review of therapy of psoriasis: the prebiologic armamentarium.
AB  - This article discusses the prebiologic armamentarium, which continues to play a
      significant role in certain patients for the treatment of psoriasis. With the
      creation of the newer"biologics," however, the treatment of psoriasis is being re
      evaluated.

PMID- 15450335
TI  - Quality-of-life issues in psoriasis.
AB  - Although the lesions of psoriasis might be "skin deep," the disease has dramatic
      physical,mental, social and financial ramifications for those it afflicts.
      Clinicians should be able to assess the impact of psoriasis on quality of life
      (QOL) to measure disease severity,monitor improvement, and ensure equitable
      funding for research and reimbursement. The development of various clinical tools
      to assess health-related QOL has led to increasing awareness of the extent of
      patient morbidity. The fact that psoriasis causes disability comparable to that
      seen in other major systemic diseases has important implications for how it
      should be viewed and treated.

PMID- 15450336
TI  - Phototherapy arsenal in the treatment of psoriasis.
AB  - Ultraviolet light has been the most used and effective treatment of psoriasis
      over the centuries. Further refinements of the delivery systems for UVB in the
      form of lasers and localized delivery through fiberoptics are beneficial in
      helping to reduce the overall exposure of noninvolved skin and permitting more
      aggressive doses of UV to the sites of disease while sparing noninvolved skin.
      Enhancement of the different modalities of UVB and psoralen plus UVA has been
      demonstrated with systemic agents, such as retinoids, but also in combination
      with immunosuppressive agents for short-term treatment to hasten the initial
      response to treatment. The advent of the biologic agents in treating psoriasis
      also introduced the opportunity for combination therapy and the theoretical
      advantage of managing T cells and antigen-presenting cells in the epidermis with
      UV light, and activated T cells in the circulation.

PMID- 15450337
TI  - Current concepts and review of alefacept in the treatment of psoriasis.
AB  - Alefacept is a novel biologic agent that selectively targets the memory T-cell
      population involved in the pathogenesis of psoriasis. Alefacept, administered by
      intramuscular (IM)or intravenous (IV) bolus injection, is safe and efficacious
      and improves quality of life ina broad spectrum of psoriasis patients. Disease
      remissions last approximately 7 months in responders following either IM or IV
      administration without further treatment. In clinical studies, treatment of
      patients with psoriasis with up to six courses of alefacept demonstrates the
      following: no evidence of an increased risk for infection or malignancy;no
      correlation between rates of infection, malignancy, and circulating CD4+ /CD8+ T
      cell counts; and low immunogenicity. A preliminary study evaluating the use of
      alefacept for the treatment of active psoriatic arthritis parallels the psoriasis
      experience and supports the premise of targeting T cells as an intervention for
      this disease. Research continues to examine the use of alefacept in combination
      with other systemic psoriasis therapies and phototherapy and its potential as a
      treatment for other T-cell-mediated diseases, such as psoriatic arthritis,
      alopecia areata, and rheumatoid arthritis.

PMID- 15450338
TI  - Current concepts and review of efalizumab in the treatment of psoriasis.
AB  - Efalizumab is a recombinant humanized monoclonal IgG1 antibody that targets
      CD11a, a cell surface protein that plays a key role in the T-cell-mediated steps
      leading to the pathogenesis of psoriasis. The efficacy and safety of efalizumab
      have been studied extensively in patients with moderate to severe chronic plaque
      psoriasis. Clinical trial data developed in several large phase 3 studies have
      demonstrated that efalizumab rapidly improves both physician- and patient
      assessed measures of clinical efficacy, and that the observed changes are
      sustainable over extended periods of continuous treatment, with a favorable
      safety profile. Efalizumab represents a new therapeutic option for the long-term
      management of moderate to severe chronic plaque psoriasis.

PMID- 15450339
TI  - Psoriasis and its treatment with infliximab-mediated tumor necrosis factor alpha
      blockade.
AB  - The pathogenesis of psoriasis, a chronic immune-mediated inflammatory skin
      disease,involves increased concentrations and activity of several proinflammatory
      cytokines,including tumor necrosis factor alpha (TNF-alpha). Infliximab is a
      chimeric human-murine TNF-alpha antibody that selectively blocks the activity of
      TNF-alpha. In controlled clinical trials, infliximab treatment has produced rapid
      and sustained improvements in psoriasis lesions and psoriatic joint involvement,
      with a favorable short-term safety and tolerability profile. Treatment with
      infliximab may be associated with an increased risk of infection or infusion
      reaction: however, the side-effect profile of infliximab in patients with
      psoriasis remains to be fully characterized, and assessment of infliximab in this
      population is currently ongoing in phase 3 studies. Comprehensive evaluation in
      controlled trials may allow infliximab to take its place among the expanding
      group of biologic drugs for the treatment of moderate to severe psoriasis.

PMID- 15450340
TI  - The treatment of psoriasis and psoriatic arthritis with etanercept: practical
      considerations on monotherapy, combination therapy, and safety.
AB  - It is quite evident the pathogenesis of psoriasis is modulated by immune-mediated
      mechanisms that invoke activated T cells and inflammatory cytokines, such as
      tumor necrosis factor-alpha. Current immunosuppressive systemic treatments may be
      effective in controlling psoriasis to a certain degree but have significant
      drawbacks, such as toxicity and relapse of the disease on discontinuation. The
      advantages of biologic agents are their greater selectivity in targeting specific
      pathways in the inflammatory cascade of psoriasis with a much higher safety
      profile. With specific antagonism directed against tumor necrosis factor-alpha,
      etanercept has demonstrated remarkable efficacy in the treatment of psoriasis and
      psoriatic arthritis.

PMID- 15450341
TI  - Current concepts and review of pimecrolimus in the treatment of psoriasis.
AB  - The ascomycine macrolactam derivative pimecrolimus has a gene profile of broad
      anti-inflammatory activity without evidence of toxicity. It exhibits excellent
      clinical tolerability after 4 weeks and 12 weeks, respectively, of oral
      treatment, and it is highly effective in a concentration-dependent manner in
      patients with moderate to severe plaque psoriasis. Although not yet approved,
      oral pimecrolimus promises to be a novel, highly effective, and well-tolerated
      drug in the systemic treatment of psoriasis and other T-cell-mediated skin
      diseases.

PMID- 15450342
TI  - Retinoid therapy for psoriasis.
AB  - This article focuses on the treatment of psoriasis with acitretin, the only
      systemic retinoid approved for psoriasis, and also briefly discusses its
      predecessor, etretinate, which was replaced by acitretin in 1997 and is no longer
      available. The use of topical tazarotene is also discussed in detail. Combination
      therapy of retinoids, both topical and systemic,with phototherapy and other
      therapeutic agents is described. In addition, new retinoid analogues that are
      undergoing clinical investigation are mentioned. Finally, potential toxicities
      and adverse effects associated with retinoids are discussed.

PMID- 15450343
TI  - Psoriatic arthritis: prevalence, diagnosis, and review of therapy for the
      dermatologist.
AB  - Psoriatic arthritis is an inflammatory arthritis that is commonly associated with
      psoriasis. While traditionally viewed as being a benign disease, recent evidence
      indicates the potential for a significant amount of morbidity and disability,
      making early recognition and intervention important. Treatment includes both
      traditional immunomodulatory agents as well as the recently available biologic
      response modifiers.

PMID- 15450344
TI  - Practical considerations in future psoriasis therapies.
AB  - Exciting new therapies are becoming available that allow dermatologists and
      patients safe and effective alternatives to traditional psoriasis therapy.
      Because these new biologic drugs are parenterally administered, practical aspects
      of their integration into clinical practice must be addressed. This article
      offers guidelines for incorporating subcutaneous,intramuscular, and intravenous
      injectables into dermatology offices. Several tiers of psoriasis care are
      outlined to encourage individual physicians to choose the optimum level of
      service compatible with their individual practices.

PMID- 15450345
TI  - Psoriasis: future research needs and goals for the twenty-first century.
AB  - Psoriasis research is entering a new era. Progress in delineating immunogenetics
      and pathomechanisms of disease brings with it a need to understand fully the
      clinical spectrum of disease and integrate phenotype with genomics and
      proteomics. Involvement of patient groups and an understanding of the
      psychosocial aspects of psoriasis, particularly its significant impairment of
      quality of life, are keys to progress. The biologic revolution in therapy of
      inflammatory disease has embraced psoriasis bringing with it an urgent need for
      evidence-base, consensus on outcome measures, and long-term real-life studies.A
      concerted effort between academia, industry, and patients will take forward the
      understanding of, and therapy for, psoriasis.

PMID- 15450346
TI  - Sclerotherapy basics.
AB  - Sclerotherapy involves the injection of a fluid into blood vessels to eradicate
      them. A thorough understanding of the basics of sclerotherapy are important when
      beginning sclerotherapy procedures in practice. This article reviews the
      essential information of sclerosants, treatment of small vessel disease, and
      patient management.

PMID- 15450348
TI  - Neuroimmunophilins: a novel drug therapy for the reversal of neurodegenerative
      disease?
AB  - Neuroimmunophilin ligands (NILs) are drugs derived from the immunosuppressant
      FK506 (tacrolimus) that have been shown to have variable efficacy in reversing
      neuronal degeneration and preventing cell death. In a wide range of animal models
      mimicking Parkinson's disease, dementia and even surgical nerve damage they
      induce re-sprouting, are neurotrophic or prevent nerve damage. The neurotrophic
      mechanism of action of these compounds is not known and may be dependent on the
      type of damage and genetic variability at the species or cellular level. Some
      evidence suggests that NILs may act through a family of proteins called FK506
      binding proteins, some of which may regulate steroid hormone receptors. Other
      evidence suggests that NILs may protect neurons by upregulating the antioxidant
      glutathione and stimulating nerve regrowth by inducing the production of
      neurotrophic factors. Initial clinical trials have had mixed success. In one,
      patients with moderately severe Parkinson's disease showed no overall improvement
      in fine motor skills following 6 months of treatment by the neuroimmunophilin GPI
      1485. But these patients did exhibit decreased loss of dopaminergic nerve
      terminals with a low dose of GPI 1485 and in fact some increase in dopaminergic
      terminals within 6 months of the higher dose of GPI 1485 drug treatment. As a
      result, a second phase II clinical trial using a patient population with less
      severe degeneration has been initiated concurrent with an investigation of GPI
      1485 and other neuroprotective therapies funded by the National Institute of
      Neurological Disorders and Stroke. Another clinical trial ongoing at this time is
      exploring the use of a neuroimmunophilin ligand to prevent nerve degeneration and
      erectile dysfunction resulting from prostatectomy. In summary, neuroimmunophilins
      show promise to reverse some forms of neurodegeneration but exact factors that
      predict outcome have not been identified.

PMID- 15450349
TI  - Lesions in the bed nucleus of the stria terminalis disrupt corticosterone and
      freezing responses elicited by a contextual but not by a specific cue-conditioned
      fear stimulus.
AB  - The bed nucleus of the stria terminalis (BNST) is believed to be a critical relay
      between the central nucleus of the amygdala (CE) and the paraventricular nucleus
      of the hypothalamus in the control of hypothalamic-pituitary-adrenal (HPA)
      responses elicited by conditioned fear stimuli. If correct, lesions of CE or BNST
      should block expression of HPA responses elicited by either a specific
      conditioned fear cue or a conditioned context. To test this, rats were subjected
      to cued (tone) or contextual classical fear conditioning. Two days later,
      electrolytic or sham lesions were placed in CE or BNST. After 5 days, the rats
      were tested for both behavioral (freezing) and neuroendocrine (corticosterone)
      responses to tone or contextual cues. CE lesions attenuated conditioned freezing
      and corticosterone responses to both tone and context. In contrast, BNST lesions
      attenuated these responses to contextual but not tone stimuli. These results
      suggest CE is indeed an essential output of the amygdala for the expression of
      conditioned fear responses, including HPA responses, regardless of the nature of
      the conditioned stimulus. However, because lesions of BNST only affected
      behavioral and endocrine responses to contextual stimuli, the results do not
      support the notion that BNST is critical for HPA responses elicited by
      conditioned fear stimuli in general. Instead, the BNST may be essential
      specifically for contextual conditioned fear responses, including both behavioral
      and HPA responses, by virtue of its connections with the hippocampus, a structure
      essential to contextual conditioning. The results are also not consistent with
      the hypothesis that BNST is only involved in unconditioned aspects of fear and
      anxiety.

PMID- 15450350
TI  - Lesions to the basolateral amygdala and the orbitofrontal cortex but not to the
      medial prefrontal cortex produce an abnormally persistent latent inhibition in
      rats.
AB  - Repeated nonreinforced preexposure to a stimulus interferes with the
      establishment of conditioned responding to this stimulus when it is subsequently
      paired with reinforcement. This stimulus-preexposure effect is known as latent
      inhibition (LI). Rather remarkably, LI appears to be resistant to the effects of
      numerous lesions, including the prefrontal cortex (PFC) and the basolateral
      amygdala (BLA). However, intact behavioral expression of LI following damage to
      given brain regions does not preclude the possibility that such regions
      participate in the regulation of LI expression in the intact brain. The present
      study showed that lesions of the BLA and the orbitofrontal cortex (OFC) but not
      of the medial PFC (mPFC) led to an abnormally persistent LI which emerged under
      conditions that disrupted LI in control rats. LI was measured in a thirst
      motivated conditioned emotional response procedure by comparing suppression of
      drinking in response to a tone in rats which received 0 (nonpreexposed) or 40
      tone presentations (preexposed) followed by either two or five tone-shock
      pairings. Control rats showed LI with 40 preexposures and two conditioning
      trials, but raising the number of conditioning trials to five disrupted LI. OFC-
      and BLA-lesioned rats showed LI under the former condition but in addition
      persisted in exhibiting LI under the latter condition. Rats with lesion of the
      mPFC did not show persistent LI. Thus, although LI does not depend on the
      integrity of BLA and OFC (because it is present in BLA- and OFC- lesioned rats
      even under conditions disrupting the phenomenon in normal rats), these regions
      play an important role in the modulation of its expression, more specifically, in
      the control of the non-expression of LI when the impact of conditioning increases
      beyond a certain level.

PMID- 15450351
TI  - Distribution of Aquaporin 9 in the adult rat brain: preferential expression in
      catecholaminergic neurons and in glial cells.
AB  - Aquaporin 9 (AQP9) is a recently cloned water channel that is permeable to
      monocarboxylate, glycerol and urea. In rat, AQP9 has been found in testis and
      liver as well as in brain where its expression has been initially shown in glial
      cells in forebrain. However, the expression of AQP9 has not been investigated in
      the brainstem. The purpose of this study is to describe the distribution of AQP9
      immunoreactive cells throughout the adult rat brain using reverse transcriptase
      polymerase chain reaction (RT-PCR), Western blot and immunohistochemistry. We
      performed immunolabeling on brain from animals perfused with fixative and we show
      that AQP9 is expressed (i) in astrocytes in the glia limitans, in the white
      matter and in glial cells of the cerebellum, (ii) in the endothelial cells of
      pial vessels, and (iii) in specific groups of neurons. The neuronal AQP9
      expression was almost exclusively observed in catecholaminergic cells including
      the adrenergic, noradrenergic and dopaminergic groups, but not in other
      monoaminergic neurons such as serotonergic or histaminergic cells. A slight
      labeling was also observed in non-catecholaminergic neurons localized in the
      paraventricular nucleus of the hypothalamus. These results indicate that AQP9 has
      a unique brain distribution with a preferential localization in catecholaminergic
      nuclei known to be involved in many cerebral functions. While the presence of
      AQP9 in glia limitans and in endothelial cells of the pial vessels could be
      related to water transport through the blood-brain barrier, its expression in
      neuronal cells, not directly involved in the osmoregulation, suggests that brain
      AQP9 could also be used as a metabolite channel since lactate and glycerol can be
      energy substrates for neurons.

PMID- 15450352
TI  - Comparative study of gene expression of cholinergic system-related molecules in
      the human spinal cord and term placenta.
AB  - By reverse transcription-polymerase chain reaction, Southern blot analysis,
      direct sequencing, and immunohistochemistry, we studied the expression of
      cholinergic neuronal markers (choline acetyltransferase [ChAT], vesicular
      acetylcholine transporter [VAChT], and a high-affinity choline transporter
      [CHT1]), and gene regulatory molecules (repressor element-1 silencing
      transcription factor/neuron-restrictive silencer factor [REST/NRSF] and CoREST)
      in the human spinal cord and term placenta, both of which are well known to
      contain cells synthesizing acetylcholine. H-type, M-type, N2-type, and R-type
      ChAT mRNAs, VAChT mRNA, and CHT1 mRNA were detected in the spinal cord, but only
      H-type, M-type, and N2-type ChAT mRNAs, in the term placenta. REST/NRSF and
      CoREST were detected in the spinal cord and the placenta, but the amounts of both
      mRNAs were greater in the placenta than in the spinal cord. Further
      microdissection analyses revealed that the placental trophoblastic cells
      contained more REST/NRSF and CoREST transcripts than the spinal large motor
      neurons. Large motor neurons in the anterior horn of the spinal cord were
      immunohistochemically stained for ChAT and VAChT. In the placenta, stromal
      fibroblasts, endothelial cells, and trophoblastic cells of the chorionic villi
      were positively stained with anti-ChAT antibody but not with anti-VAChT antibody.
      These findings suggest that transcriptions of the R-type ChAT and VAChT mRNAs are
      coordinately suppressed in the human term placenta, which might be regulated in
      part by a REST/NRSF complex that binds to a consensus sequence of repressor
      element 1/neuron-restrictive silencer element (RE1/NRSE) in the 5' region
      upstream from exon R, whereas transcriptions of the H-type, M-type, and N2-type
      ChAT mRNAs might be independent of control by RE1/NRSE. It is possible that at
      least two separate regulatory mechanisms of gene expression are present for the
      human cholinergic gene locus, which might be selected by different combinations
      of DNA motifs and binding proteins to function in neuronal and non-neuronal
      cells.

PMID- 15450353
TI  - Bursts of recurrent excitation in the activation of intrinsic sensory neurons of
      the intestine.
AB  - Sensory neurons intrinsic to the wall of the intestine receive input from stimuli
      in the lumen. These stimuli interact with the mucosal epithelium causing release
      of sensory mediators that depolarize the sensory nerve terminals. The
      depolarization and the subsequent pattern of action potential (AP) discharge
      controls the type and magnitude of the reflex evoked. The characteristics of this
      AP discharge were investigated in 60 intrinsic sensory neurons from the myenteric
      plexus of the guinea-pig ileum. Intracellular electrophysiological recordings
      were made from neurons near intact mucosa during electrical stimulation of the
      mucosa and/or neuronal soma. Most neurons (87%) responded to mucosal stimulation
      with a burst of 3.8+/-0.3 APs (average instantaneous frequency, fINT 39+/-4 Hz).
      In 38%, a somatically evoked AP triggered a similar burst of 2.9+/-0.3 APs (fINT
      52+/-6 Hz) while in 50% of neurons, there was ongoing spontaneous bursting (3.8+/
      0.2 APs, fINT 48+/-6 Hz). APs in all of these bursts had an inflection on the
      rising phase and they persisted during somatic hyperpolarization indicating they
      were generated in a distal process rather than the soma. Collision experiments
      confirmed this and suggested that bursts originated near the mucosal sensory
      nerve terminals. A reduction in membrane excitability reduced the number of APs
      in a burst suggesting a brief depolarizing event, such as a voltage- or ligand
      gated ion channel, was responsible. Bursting behavior in the intrinsic sensory
      neurons is common for mucosal stimuli and may involve a novel transmitter acting
      at the sensory nerve terminal. Further, some bursting involves positive feedback
      between the nerve terminals and other elements in the epithelium. This is a novel
      and potentially important component of intestinal sensory transduction.

PMID- 15450354
TI  - Gene deletion of cystatin C aggravates brain damage following focal ischemia but
      mitigates the neuronal injury after global ischemia in the mouse.
AB  - Cystatin C is distributed in all human tissues and fluids with a particular
      abundance in the cerebrospinal fluid. Cystatin C is a strong endogenous inhibitor
      of lysosomal cysteine proteases, such as cathepsin B, L, H and S, that are
      involved in various biological processes such as degradation of cellular proteins
      and regulation of enzymes, as well as in pathological processes. Pharmacological
      inhibition of cathepsins has been shown to reduce neuronal damage after brain
      ischemia, suggesting that cystatin C is an endogenous neuroprotectant. Cystatin C
      has also amyloidogenic properties and is co-localized with beta-amyloid in
      degenerated neurons in Alzheimer's disease, suggesting a role in neuronal
      degeneration. To test the hypothesis that endogenous cystatin C is
      neuroprotective during brain ischemia, global and focal brain ischemia was
      induced in mice with the cystatin C gene knocked out. Following focal ischemia,
      larger brain infarcts were found in cystatin C knockout mice, probably due to a
      reduced inhibition of the cathepsins during ischemia. In contrast, brain damage
      after global ischemia was diminished in cystatin C knockout mice, suggesting that
      cystatin C has an aggravating effect on selective neuronal damage after global
      ischemia.

PMID- 15450355
TI  - Nitric oxide in the cerebral cortex of amyloid-precursor protein (SW) Tg2576
      transgenic mice.
AB  - Changes in the amyloid-peptide (Abeta), neuronal and inducible nitric oxide
      (NO)synthase (nNOS, iNOS), nitrotyrosine, glial fibrillary acidic protein, and
      lectin from Lycopersicon esculentum (tomato) were investigated in the cerebral
      cortex of transgenic mice (Tg2576) to amyloid precursor protein (APP), by
      immunohistochemistry (bright light, confocal, and electron microscopy). The
      expression of nitrergic proteins and synthesis of nitric oxide were analyzed by
      immunoblotting and NOS activity assays, respectively. The cerebral cortex of
      these transgenic mice showed an age-dependent progressive increase in
      intraneuronal aggregates of Abeta-peptide and extracellular formation of senile
      plaques surrounded by numerous microglial and reactive astrocytes. Basically, no
      changes to nNOS reactivity or expression were found in the cortical mantle of
      either wild or transgenic mice. This reactivity in wild mice corresponded to
      numerous large type I and small type II neurons. The transgenic mice showed
      swollen, twisted, and hypertrophic preterminal and terminal processes of type I
      neurons, and an increase of the type II neurons. The calcium-dependent NOS
      enzymatic activity was higher in wild than in the transgenic mice. The iNOS
      reactivity, expression and calcium-independent enzymatic activity increased in
      transgenic mice with respect to wild mice, and were related to cortical neurons
      and microglial cells. The progressive elevation of NO production resulted in a
      specific pattern of protein nitration in reactive astrocytes. The ultrastructural
      study carried out in the cortical mantle showed that the neurons contained
      intracellular aggregates of Abeta-peptide associated with the endoplasmic
      reticulum, mitochondria, and Golgi apparatus. The endothelial vascular cells also
      contained Abeta-peptide deposits. This transgenic model might contribute to
      understand the role of the nitrergic system in the biological changes related to
      neuropathological progression of Alzheimer's disease.

PMID- 15450356
TI  - Analysis of cytochrome C oxidase subunits III and IV expression in developing rat
      brain.
AB  - Cytochrome c oxidase (COX) complex is built up with both nucleus- and
      mitochondrion-encoded subunits. Biogenesis and assembly of the complex thus
      requires fine cross-talk between the two compartments. In order to shed light on
      the regulation of nuclear-mitochondrial interactions, we studied the expression
      of COXIII (mitochondrion-encoded) and COXIV (nucleus-encoded) in adult rat
      tissues and rat developing brain. We found that the levels of COXIV protein and
      mRNA are not linearly related, thus suggesting a post-transcriptional mode of
      regulation. In agreement with this observation, we report the presence of a
      protein that specifically binds to the 3'-untranslated region of COXIV mRNA. This
      factor, that forms with RNA a complex of about 60 kDa, is present both in the
      cytoplasm and mitochondria, where its concentration decreases throughout
      development with inverse correlation with COXIV accumulation. Interestingly,
      using an antibody raised in our laboratory, we found that, in developing rat
      brain, COXIII does not localize exclusively to mitochondria, but is also present
      in the cytosol, where it could exert a yet unknown regulatory role.

PMID- 15450357
TI  - Adrenal medulla calcium channel population is not conserved in bovine chromaffin
      cells in culture.
AB  - During the stress response adrenal medullary chromaffin cells release
      catecholamines to the bloodstream. Voltage-activated calcium channels present in
      the cell membrane play a crucial role in this process. Although the
      electrophysiological and pharmacological properties of chromaffin cell calcium
      channels have been studied in detail, the molecular composition of these channels
      has not been defined yet. Another aspect that needs to be explored is the extent
      to which chromaffin cells in culture reflect the adrenal medulla calcium channel
      characteristics. In this sense, it has been described that catecholamine release
      in the intact adrenal gland recruits different calcium channels than those
      recruited during secretion from cultured chromaffin cells. Additionally, recent
      electrophysiological studies show that chromaffin cells in culture differ from
      those located in the intact adrenal medulla in the contribution of several
      calcium channel types to the whole cell current. However there is not yet any
      study that compares the population of calcium channels in chromaffin cells with
      that one present in the adrenal medulla. In order to gain some insight into the
      roles that calcium channels might play in the adrenal medullary cells we have
      analyzed the alpha1 subunit mRNA expression profile. We demonstrate that the
      expression pattern of voltage-dependent calcium channels in cultured bovine
      chromaffin cells markedly differs from that found in the native adrenal medulla
      and that glucocorticoids are only partially involved in those differences.
      Additionally, we show, for the first time, that the cardiac isoform of L-type
      calcium channel is present in both bovine adrenal medulla and cultured chromaffin
      cells and that its levels of expression do not vary during culture.

PMID- 15450358
TI  - Corticotropin-releasing factor receptor type 1 and 2 mRNA expression in the rat
      anterior pituitary is modulated by intermittent hypoxia, cold and restraint.
AB  - We had previously demonstrated that continual-hypoxia stimulated corticotropin
      releasing factor (CRF)mRNA in hypothalamus, and release of CRF, as well as
      enhancing plasma adrenocorticotropic-hormone and corticosterone of rats. The
      present study demonstrates using in situ autoradiography that CRF receptor 1
      (CRFR1) and CRF receptor 2 (CRFR2) mRNA in the rat anterior pituitary is changed
      by intermittent hypoxia, cold, restraint, alone and in combination. Rats were
      exposed to intermittent hypoxia for 4 h/day during various periods in a hypobaric
      chamber. Hypoxia equivalent to an altitude of around 2 km (16.0% O2) or 5 km
      (10.8% O2) caused a biphasic change in both CRFR1 and R2 mRNA, there being an
      initial significant decline on day 1 and then an enhancement by day 2. The
      increase of both receptor subtypes mRNA was relatively well maintained up to 15
      days in rats exposed to 2 km intermittently. CRFR2 mRNA in rats exposed to 5 km,
      after peaking at day 2 therefore declined and was not different to controls at 15
      days. Five kilometer hypoxia markedly reduced body weight gain. The increased
      CRFR1 mRNA was also induced by restraint alone, hypoxia+restraint and
      hypoxia+cold but not by cold alone. The CRFR2 mRNA was significantly increased by
      all the stresses except for hypoxia+restraint. These results show that the acute
      response to intermittent hypoxia is a decrease in the CRF receptor mRNA whereas
      longer exposure to the three environmental stressors hypoxia, cold and restraint
      is needed to provoke an increase. This may have important consequences for
      adaptation to high altitude. The significant differences between the expression
      of CRFR1 mRNA and CRFR2 mRNA in response to the different stimuli might suggest
      that the two receptors in the pituitary play different roles in behavior.

PMID- 15450359
TI  - Individual differences in the effects of serotonergic anxiolytic drugs on the
      motivation to self-administer cocaine.
AB  - Numerous clinical studies have indicated that lifetime anxiety is highly
      prevalent in drug addicts. In the treatment of drug abuse, dually diagnosed drug
      addicts may benefit from pharmacological intervention strategies that alleviate
      the psychiatric symptomatology. We have previously shown that rats with different
      coping strategies in a stressful environment show strong differences in the
      motivation to self-administer cocaine. That is, cocaine self-administration under
      a progressive ratio (PR) schedule of reinforcement was enhanced in high grooming
      (HG) rats as compared with low grooming (LG) rats. To identify the
      pharmacological basis of these differences, we tested the acute effects of
      several anxiolytic drugs on cocaine self-administration in HG and LG rats under a
      PR schedule of reinforcement. Chlordiazepoxide increased PR responding in both
      the HG and LG rats, while the selective corticotrophin releasing hormone 1
      receptor antagonist R121919 had no effect on cocaine self-administration under
      the PR schedule. Interestingly, buspirone and fluoxetine decreased PR responding
      in HG rats only and thereby abolished the individual differences in PR responding
      between HG and LG rats. In support of the differential effects of the
      serotonergic drugs on PR responding in HG and LG rats, we found that the in vitro
      electrically evoked release of [3H]serotonin from mesocorticolimbic brain slices
      was reduced in the medial prefrontal cortex, substantia nigra and nucleus
      accumbens core, and increased in the nucleus accumbens shell of HG rats relative
      to LG rats. These findings show that serotonergic anxiolytics abolish the pre
      existing individual differences in cocaine self-administration between HG and LG
      rats, which show differences in the reactivity of serotonergic neurons. This
      suggests that the effectiveness of pharmacological interference may depend on the
      neurochemical and motivational state of the individual.

PMID- 15450360
TI  - Peripheral secretin-induced Fos expression in the rat brain is largely vagal
      dependent.
AB  - I.v. injection of secretin activates neurons in brain areas controlling autonomic
      function and emotion. Peripheral administration of secretin inhibits gastric
      functions through a central mechanism that is mediated by vagal dependent
      pathways. We investigated whether the vagus nerve is involved in i.p. injection
      of secretin-induced brain neuronal activation in conscious rats as monitored by
      Fos immunohistochemistry. Secretin (40 or 100 microg/kg, i.p., 90 min) induced a
      dose-related increase in the number of Fos positive neurons in the central
      nucleus of the amygdala (CeA), and a plateau Fos response in the area postrema
      (AP), nucleus tractus solitarii (NTS), locus coeruleus (LC), Barrington's nucleus
      (Bar), external lateral subnucleus of parabrachial nucleus (PBel) and arcuate
      nucleus, and at 100 microg/kg, in the dorsal motor nucleus of the vagus (DMV)
      compared with i.p. injection of vehicle. Double immunohistochemistry showed that
      secretin (40 microg/kg, i.p.) activates tyrosine hydroxylase neurons in the NTS.
      Subdiaphragmatic vagotomy (7 days) abolished Fos expression-induced by i.p.
      secretin (40 microg/kg) in the NTS, DMV, LC, Bar, PBel and CeA, while a
      significant rise in the AP was maintained. In contrast, s.c. capsaicin (10 days)
      did not influence the Fos induction in the above nuclei. Reverse transcription
      polymerase chain reaction (RT-PCR) and quantitative real-time PCR showed that
      secretin receptor mRNA is expressed in the nodose ganglia and levels were higher
      in the right compared with the left ganglion. These results indicate that
      peripheral secretin activates catecholaminergic NTS neurons as well as neurons in
      medullary, pontine and limbic nuclei regulating autonomic functions and emotion
      through vagal-dependent capsaicin-resistant pathways. Secretin injected i.p. may
      signal to the brain by interacting with secretin receptors on vagal afferent as
      well as on AP neurons outside the blood-brain barrier.

PMID- 15450361
TI  - Binding, internalization, and membrane incorporation of human immunodeficiency
      virus-1 at the blood-brain barrier is differentially regulated.
AB  - Human immunodeficiency virus (HIV)-1 within the CNS induces neuro-acquired
      immunodeficiency syndrome and acts as a reservoir for reinfection of peripheral
      tissues. HIV-1 crosses the blood-brain barrier (BBB) within infected immune cells
      and as cell-free virus by a CD4-independent mechanism. Which proteins control
      free virus transport across the BBB are unknown, but work with wheatgerm
      agglutinin (WGA) and heparin suggests that heparan sulfate proteoglycans, sialic
      acid, and N-acetyl-beta-D-glucosaminyl acid bind HIV-1. Here, we found that an
      HIV-1 T-tropic virus was taken up by mouse brain endothelial cells in vitro and
      crossed the BBB in vivo and could be effluxed as intact virus. Uptake was
      stimulated by WGA and protamine sulfate (PS) and inhibited by heparin. BBB uptake
      of virus involved four distinguishable binding sites: i) reversible cell surface
      binding involving gp120 and sensitive to PS/heparin but insensitive to WGA;
      internalization with a ii) WGA-sensitive site binding gp120 and iii) a PS/heparin
      sensitive site not involving gp120; iv) membrane incorporation not affected by
      WGA, heparin, or PS. In conclusion, binding, internalization, and membrane
      incorporation are separately regulated steps likely determining whether HIV-1 is
      incorporated into brain endothelial cells, transported across them, or returned
      to the circulation.

PMID- 15450362
TI  - Hepatocyte growth factor as an enhancer of nmda currents and synaptic plasticity
      in the hippocampus.
AB  - Hepatocyte growth factor (HGF) promotes the survival and migration of immature
      neurons, but its role in the mature brain has remained elusive. In the
      hippocampus of juvenile rats, we found that the HGF receptor c-Met was expressed
      in neurons. Furthermore, it was highly Tyr-phosphorylated, more so than in the
      liver under normal conditions, suggesting that the receptor is activated and that
      HGF may act continuously in the intact brain. Exogenously applied HGF enhanced
      synaptic long-term potentiation (LTP) in the CA1 region of hippocampus, but did
      not affect long-term depression. We further found that HGF augmented N-methyl-D
      aspartate receptor-mediated currents in both slices and dissociated neurons. This
      augmentation is likely to underlie the enhancement of LTP. Considering that the
      expression of both HGF and c-Met are known to be induced by ischemic stimuli,
      this modulation would provide a novel understanding of a neuronal regulatory
      systems shared with pathogenic ischemic states.

PMID- 15450363
TI  - Effect of erythropoietin on nitric oxide production in the rat hippocampus using
      in vivo brain microdialysis.
AB  - In order to investigate the role of erythropoietin (EPO) in the hippocampus, we
      studied the effect of EPO on nitric oxide (NO) production in the rat hippocampus
      using brain microdialysis. The dialysis probe was stereotaxically inserted into
      the rat hippocampus 24 h before the dialysis experiment. The perfusion fluid
      (Krebs-HEPES buffer, pH 7.4) was collected at 15-min intervals under freely
      moving conditions and NO metabolites (NOx) in the perfusate were immediately
      measured using a NOx-analyzing high performance liquid chromatography
      (HPLC)system. Following the collection of four fractions, 1 microl of EPO (10(
      10) M, 10(-8) M and 10(-6) M) or vehicle (saline) was gently injected into the
      hippocampal tissue. The perfusion fluid was collected for 3 h after the
      injection. The NOx levels were unchanged by the injection of vehicle alone. After
      the injection of EPO, NOx levels gradually increased. The EPO-induced increase in
      NOx levels was significant at 10(-6) M EPO. The EPO-induced increases in NOx
      levels were eliminated in the presence of anti-EPO antibody. The increase in NOx
      levels induced by EPO was blunted by nicardipine, a Ca2+ channel blocker, but not
      by MK-801, an antagonist of N-methyl-D-aspartate (NMDA) receptors. These
      findings, taken together, suggest that EPO increased NO production in the rat
      hippocampus by activating voltage-gated Ca2+ channels, but not through NMDA
      receptors.

PMID- 15450364
TI  - Peripheral glutamate receptors contribute to mechanical hyperalgesia in a
      neuropathic pain model of the rat.
AB  - We hypothesized that glutamate (Glu) released from the peripheral terminals of
      primary afferents contributes to the generation of mechanical hyperalgesia
      following peripheral nerve injury. Nerve injury was performed on rats with a
      lumbar 5 spinal nerve lesion (L5 SNL), which was preceded by L5 dorsal rhizotomy
      (L5 DR) to avoid the potential central effects induced by L5 SNL through the L5
      dorsal root. Mechanical hyperalgesia, as evidenced by a reduction in paw
      withdrawal threshold (PWT), was short-lasting (<6 days) after L5 DR, but
      persistent (>42 days) after L5 SNL preceded by L5 DR. When an intraplantar
      injection into the affected hind paw was given immediately before L5 SNL, non
      competitive N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 (20 nmol),
      group-I metabotropic Glu (mGlu) receptor antagonist DL-amino-3-phosphonopropionic
      acid (DL-AP3; 70 nmol), and selective group-II mGlu receptor agonist 4
      aminopyrrolidine-2,4-dicarboxylate (APDC; 20 nmol) delayed the onset of PWT
      reduction for 1-4 days. However, this onset was not affected by alpha-amino-3
      hydroxy-5-methylisoxazole-4-propionic acid/kainate receptor antagonist 2,3-dioxo
      6-nitro-1,2,3,4,-tetrahydrobenzo[f]quinoxaline-7-sulfonamide (NBQX; 100 nmol).
      When the same injection was given after L5 SNL-induced mechanical hyperalgesia
      had been established, MK-801 reversed the PWT reduction for 30-75 min, whereas
      NBQX, DL-AP3, or APDC had no effect. These results suggest that the manipulation
      of the peripheral Glu receptors reduces neuropathic pain, by blocking NMDA and
      group-I mGlu receptors and by stimulating group-II mGlu receptor during the
      induction phase of neuropathic pain, but only by blocking the NMDA receptor
      during its maintenance phase.

PMID- 15450365
TI  - Cortical responses to noxious stimuli during sleep.
AB  - We used magnetoencephalography to study effects of sleep on cortical responses to
      noxious stimuli and to clarify the mechanisms underlying pain perception. For a
      noxious stimulus, painful intra-epidermal electrical stimulation, which
      selectively activates A-delta fibers, was applied to the dorsum of the left hand.
      While awake, subjects were asked to count the number of stimuli silently
      (Attention) or ignore the stimuli (Control). During sleep, magnetic fields
      recorded in stage 1 sleep and stage 2 sleep were analyzed. One main component at
      a latency around 140-160 ms was identified in the awake condition. Multiple
      source analysis indicated that this main component was generated by activities in
      the contralateral primary somatosensory cortex (SI), bilateral secondary
      somatosensory cortex (SII) and insular cortex. The medial temporal area (MT) and
      cingulate cortex were activated later than the main component. Cortical responses
      in the contralateral SI, ipsilateral SII and MT, bilateral insula and cingulate
      cortex were significantly enhanced in Attention as compared with Control. The
      main component 1 M as well as later magnetic fields were markedly attenuated
      during sleep, suggesting that all these cortical areas are involved in pain
      cognition.

PMID- 15450366
TI  - Influence of the entorhinal cortex on accumbal and striatal dopaminergic
      responses in a latent inhibition paradigm.
AB  - The use of latent inhibition paradigms is one means of investigating the
      involvement of mesencephalic dopaminergic (DA) neurons in cognitive processes. We
      have shown recently that DA neurons reaching the core and the dorsomedial shell
      parts of the nucleus accumbens and the anterior part of the striatum are
      differentially involved in latent inhibition. In other respects, theoretical,
      behavioral and anatomo-functional data suggest that the entorhinal cortex (ENT)
      may control latent inhibition expression. In this study, using in vivo
      voltammetry in freely moving rats, we investigated the influence of the ENT on
      the DA responses obtained in the core and dorsomedial shell parts of the nucleus
      accumbens and the anterior part of the striatum. For this purpose a reversible
      inactivation of the left ENT was achieved by the local microinjection of
      tetrodotoxin, 3 h before pre-exposure to the conditional stimulus (banana odour).
      During the second session, animals were aversively conditioned to banana odour.
      Results obtained during the third session (test session), in animals submitted to
      the reversible blockade of the ENT before the first session were as follows: (1)
      pre-exposed conditioned animals displayed behavioral aversive responses; (2)
      where core DA responses were concerned, responses were situated between those
      observed in pre-exposed and non-pre-exposed conditioned animals; (3) by contrast,
      where the dorsomedial shell part of the nucleus accumbens and the anterior
      striatum were concerned, DA variations were not statistically different in pre
      exposed and non-pre-exposed conditioned rats. These data suggest that the left
      ENT exerts a crucial influence over the latent-inhibition-related DA responses in
      the left dorsomedial shell part of the nucleus accumbens and the left anterior
      part of the striatum, whereas one or more other brain regions control DA
      variations in the left core part of the nucleus accumbens. These data may help us
      to understand the pathophysiology of schizophrenic psychoses.

PMID- 15450367
TI  - Age-related changes in nigrostriatal dopaminergic function are accentuated in +/-
      brain-derived neurotrophic factor mice.
AB  - The effects of a deletion for the brain derived neurotrophic factor (BDNF) allele
      (+/- BDNF) upon age-related changes in nigrostriatal dopaminergic (NSDA) function
      were assessed. Behavioral (beam crossing and spontaneous activity) and
      neurochemical (potassium-stimulated dopamine release from superfused striatum)
      measures were compared among Young (4-5 month), Middle (11-13 month) and Aged (19
      21 month) +/- BDNF and their wild type littermate control (+/+ BDNF) mice. No
      statistically significant differences were obtained between +/+ and +/- BDNF mice
      at the Young age sampling period for any of the behavioral or neurochemical
      measures. Behavioral and neurochemical responses indices of NSDA function begin
      to diverge between +/+ and +/- Middle age BDNF mice and maximal differences were
      observed at the Aged period. For both movement and stereotypy times, scores
      obtained from +/+ mice were significantly decreased compared with +/- BDNF mice
      at the Aged period and center time scores of +/+ mice were decreased at both the
      Middle and Aged periods compared with +/- BDNF mice. Neurochemically, potassium
      stimulated DA release of +/+ mice was significantly greater than +/- BDNF mice
      with maximal differences obtained at the Aged period. These results demonstrate
      marked differences in age-related changes of NSDA function between +/+ and +/-
      BDNF mice and suggest that the deletion of one allele for BDNF may make these
      mice more susceptible to age-related declines in NSDA function.

PMID- 15450368
TI  - Capillary level imaging of local cerebral blood flow in bicuculline-induced
      epileptic foci.
AB  - Local hemodynamics of the cerebral cortex is the basis of modern functional
      imaging techniques, such as fMRIand PET. Despite the importance of local
      regulation of the blood flow, capillary level quantification of cerebral blood
      flow has been limited by the spatial resolution of functional imaging techniques
      and the depth penetration of conventional optical microscopy. Two-photon laser
      scanning microscopic imaging technique has the necessary spatial resolution and
      can image capillaries in the depth of the cortex. We have loaded the serum with
      fluorescein isothiocyanate dextran and quantified the flow of red blood cells
      (RBCs) in capillaries in layers 2/3 of the mouse somatosensory cortex in vivo.
      Basal capillary flux was quantified as approximately 28.9+/-13.6 RBCs/s (n=50,
      mean+/-S.D.) under ketamine-xylazine anesthesia and 26.7+/-16.0 RBCs/s (n=31)
      under urethane anesthesia. Focal interictal (epileptiform) activity was induced
      by local infusion of bicuculline methochloride in the cortex. We have observed
      that capillary blood flow increased as the cortical local field events developed
      into epileptiform in the vicinity of GABA receptor blockade (<300 microm from the
      administration site). Local blood flow in the interictal focus increased
      significantly (42.5+/-18.5RBCs/s, n=52) relative to the control conditions or to
      blood flow measured in capillaries at distant (>1mm from the focus) sites from
      the epileptic focus (27.8+/-12.9 RBCs/s, n=30). These results show that hyper
      synchronized neural activity is associated with increased capillary perfusion in
      a localized cortical area. This volume is significantly smaller than the
      currently available resolution of the fMRI signal.

PMID- 15450369
TI  - Preliminary studies of the 2D crystallization of Omp1 of Serratia marcescens:
      observation by atomic force microscopy in native membranes environment and
      reconstituted in proteolipid sheets.
AB  - In this work the porin Omp1 of Serratia marcescens was expressed in a porin
      deficient mutant (Escherichia coli UH302) and its functionality studied following
      the accumulation of ciprofloxacin in bacteria. The protein was extracted,
      purified and reconstituted in proteoliposomes of different composition
      (lipopolysaccharide (LPS), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine
      (POPC) and, 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC)). Maximum
      extraction of the detergent was achieved applying different steps of dialysis and
      centrifugation. Proteolipid sheets with different composition were spread onto
      mica and observed by atomic force microscopy. Two-dimensional crystal of Omp1 was
      not observed in any case due to low resolution achieved. Judging from the images
      features POPC is the most suitable phospholipid to enhance 2D lattice formation
      for Omp1.

PMID- 15450370
TI  - Capacitance-derived dielectric constants demonstrate differential preinitiation
      complexes in TBP-independent and TBP-dependent transcription.
AB  - The electronic properties of proteins and DNA may change dramatically upon
      complex formation, yet there are not many experimental methods which can be used
      to measure these properties. It has been previously shown that measuring the
      capacitance of a solution containing interacting DNA and protein species can
      yield information about changing dipole moments. The measured dielectric constant
      relates directly to the dipole moment of the complexes in solution. Here, we
      apply this method to partial transcription initiation complexes in order to
      investigate the changing electronic properties in the transcriptional
      preinitiation complex. These experiments are the first reported observations
      relating to the overall dipole moment and its changes in preinitiation complex
      formation. Comparing results from TBP-independent and TBP-dependent
      transcriptional systems shows a divergence in the electronic properties of built
      up transcription complexes, suggesting that they initiate transcription by
      significantly different electronic and structural pathways.

PMID- 15450371
TI  - Modulation of tetracycline-phospholipid interactions by tuning of pH at the water
      air interface.
AB  - This paper is part of a systematic study of the interactions of tetracycline
      antibiotics with phospholipid monolayers at the water-air interface.
      Tetracyclines are widespread antibiotics that undergo a series of protonation
      equilibria in solution, depending on the pH. The surface activity of
      tetracyclines was determined by means of surface tension measurements for three
      different systems, i.e. water, TRIS and McIlvaine-EDTA buffer. Surface pressure
      molecular area and surface potential-molecular area isotherms were acquired for
      dipalmitoylphosphatidic acid monolayers on TRIS buffer (pH=7.0) and McIlvaine
      EDTA buffer (pH=4.0) solution as a function of tetracycline concentration in the
      subphase. Comparative analysis of surface potential data, with the molecular
      dipole moment of tetracycline obtained from semiempirical calculations, provided
      information on the orientation of tetracycline at the interface. Surface pressure
      measurements as a function of monolayer compression were described, applying
      either a continuous partition model or Langmuir adsorption isotherms. The results
      obtained in the case of buffer solutions were compared to those obtained for
      tetracycline in water subphases. The analysis of the results indicated that
      electrostatic interactions dictate the migration of tetracycline to the monolayer
      interface. Penetration of the molecule to the lipophilic portion of the monolayer
      was unlikely, especially at high surface pressures. The results showed that
      stronger interactions are established between the zwitterionic tetracycline and
      the deprotonated phosphatidic group in TRIS buffer solution; in this case,
      tetracycline binds at the monolayer interface following a Langmuir type
      adsorption. In the case of water, where the monodeprotonated acid and the
      tetracycline zwitterions are the only species involved, the data can be described
      by continuous partition of tetracycline between interfacial and bulk phases. The
      same holds for McIlvaine-EDTA buffer subphases, although the high concentrations
      of citrate ions in this buffer competitively interfere with tetracycline
      association at the monolayer interface.

PMID- 15450372
TI  - Boronphenylalanine insertion in cationic liposomes for Boron Neutron Capture
      Therapy.
AB  - Cationic liposomes are widely used as carriers of biomolecules specifically
      targeted to the cell nucleus. p-Boronphenylalanine (BPA) is a powerful anti-tumor
      agent for Boron Neutron Capture Therapy (BNCT). In this paper, (1)H and (13)C NMR
      was used to study the insertion of BPA in mixed liposomes, made up by the
      positively charged 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and the
      zwitterionic 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE). The boronated
      drug was distributed between the water phase and the liposomes. The location site
      of BPA into the lipid bilayer was investigated and the boron-substituted aromatic
      ring was found inserted in the hydrophobic region, whereas the amino acidic group
      was oriented towards the aqueous environment. Further information was given by
      proton spin-lattice relaxation rates.

PMID- 15450373
TI  - Low frequency ultrasound induces aggregation of porcine fumarase by free radicals
      production.
AB  - Hydrogen peroxide and hydroxyl-free radicals determine a diffuse aggregation of
      porcine fumarase and a loss of its enzymatic activity. In this study, hydroxyl
      free radicals were generated "in situ" by irradiation with ultrasound (US) at 38
      kHz. The structural characteristics of aggregated fumarase were studied using
      circular dichroism spectroscopy (CD) and steady state fluorescence spectroscopy.
      Enzyme aggregation is caused by the formation of intermolecular disufide bridges,
      originated by the oxidation of cysteine residues, together with a diffuse
      increase in beta-turn in the protein's secondary structure. These conformational
      changes lead to a fibrous, amyloid-like aggregation which appears ordered and
      regular under TEM microscopy.

PMID- 15450374
TI  - ESR studies on the effect of cholesterol on chlorpromazine interaction with
      saturated and unsaturated liposome membranes.
AB  - In this study, the effects of chlorpromazine (CPZ) on lipid order and motion in
      saturated (DMPC, DMPG) and unsaturated (SOPC) liposome membranes were
      investigated by electron spin resonance (ESR) spin labeling technique. We have
      shown that above the main phase transition temperature of membrane lipids (T(M)),
      CPZ slightly increases lipid order in membranes without cholesterol, whereas
      below T(M) it has a strong opposite effect. Addition of 30 mol% of cholesterol
      into DMPC and SOPC membranes changes significantly the CPZ effects both above and
      below T(M). Additionally, above T(M), the ordering effect of CPZ on pure SOPC
      membrane is stronger at pH 7.4 than at pH 9.0, whereas below T(M), as well as in
      the presence of cholesterol, pH does not seem to play a role in CPZ effect on
      both membranes. Because of the strong influence of membrane composition on CPZ
      effect on membranes, the use of cholesterol as a marker of CPZ photosensitized
      reactions has been discussed.

PMID- 15450375
TI  - Proton dependence of tobacco mosaic virus dissociation by pressure.
AB  - Tobacco mosaic virus (TMV) is an intensely studied model of viruses. This paper
      reports an investigation into the dissociation of TMV by pH and pressure up to
      220 MPa. The viral solution (0.25 mg/ml) incubated at 277 K showed a significant
      decrease in light scattering with increasing pH, suggesting dissociation. This
      observation was confirmed by HPLC gel filtration and electron microscopy. The
      calculated volume change of dissociation (DeltaV) decreased (absolute value) from
      -49.7 ml/mol of subunit at pH 3.8 to -21.7 ml/mol of subunit at pH 9.0. The
      decrease from pH 9.0 to 3.8 caused a stabilization of 14.1 kJ/mol of TMV subunit.
      The estimated proton release calculated from pressure-induced dissociation curves
      was 0.584 mol H(+)/mol of TMV subunit. These results suggest that the degree of
      virus inactivation by pressure and the immunogenicity of the inactivated
      structures can be optimized by modulating the surrounding pH.

PMID- 15450376
TI  - Binding mode of cationic monomer and dimer porphyrin with native and synthetic
      polynucleotides studied by polarized light spectroscopy.
AB  - Binding properties of the tricationic porphyrin monomer with a phenolic
      substituent at the periphery and the porphyrin dimer conjugated with hydrophilic
      triethylene glycol were investigated in this study using absorption and polarized
      spectroscopy, namely, circular dichroism (CD) and linear dichroism (LD). The
      spectral properties of the porphyrin monomer, when complexed with
      polynucleotides, were essentially the same as that of the well-known meso
      tetrakis(N-methylpyridiniumyl)porphyrin, indicating that the substitution at one
      peripheral pyridiniumyl ring did not affect the binding mode. When the porphyrin
      dimer formed a complex with poly[d(G-C)(2)], a negative CD band and a negative
      LD(r) spectrum were apparent in the Soret absorption region, with its LD(r)
      magnitude significantly smaller than that in the DNA absorption region. As the
      complex was stabilized over time, the intensity of the negative CD band and the
      negative LD(r) increased. These observations indicated that one of the porphyrin
      moieties of the dimer intercalated initially and than the other one also
      intercalated consecutively within a few hours. In the porphyrin dimer-poly[d(A
      T)(2)] complex case, a bisignate CD was apparent and remained for at least 12 h,
      indicating that the porphyrins are stacked along the polynucleotide stem even at
      a very low [porphyrin]/[DNA base] ratio. A wavelength-dependent and time
      dependent LD(r) of this complex suggests that the porphyrin molecular plane tilts
      strongly relative to the polynucleotide helix axis. The spectral properties of
      the porphyrin dimer-DNA complex are similar to those of the porphyrin dimer
      poly[d(G-C)(2)] complex. However, some of the porphyrin moieties were located at
      the groove, which was evident by some positive characters in the CD and LD(r)
      spectra at the short wavelength in the Soret band.

PMID- 15450377
TI  - Vibrational circular dichroism spectra of protein films: thermal denaturation of
      bovine serum albumin.
AB  - Vibrational circular dichroism (VCD) spectroscopy has been used for the first
      time to investigate the thermal denaturation of proteins in H(2)O solutions.
      Films prepared from heated aqueous solutions were used for these investigations.
      A well-known alpha-helical protein, bovine serum albumin (BSA), is used for this
      first study. Both VCD and infrared absorption results obtained for BSA films
      indicate that the heat treatment of BSA induces significant amounts of beta-sheet
      structure and that the denaturation process is irreversible. To verify the
      irreversible nature of thermal denaturation, optical rotation was also measured
      as a function of temperature in both heating and cooling cycles. These results
      also indicate that thermal denaturation of BSA in solution is irreversible. This
      study establishes the usefulness of films for VCD investigations and offers new
      avenues for VCD studies on biologically important systems.

PMID- 15450378
TI  - Jack bean urease (EC 3.5.1.5) aggregation monitored by dynamic and static light
      scattering.
AB  - Aggregation of jack bean urease (JBU) is involved in many alterations of its
      biological properties, notably the ureolytic and entomotoxic activities. In order
      to investigate this phenomenon, protein aggregates were characterized by dynamic
      (DLS) and static light scattering (SLS) spectroscopies through determination of
      apparent hydrodynamic radii, the average molecular masses, radii of gyration and
      second virial coefficients. No effect of disulfide reducing agents on protein
      association was observed contrasting with previous reports implicating their
      function in the prevention of JBU aggregation. The influence of freeze-thawing
      cycles on protein aggregation was also investigated. Our results showed that
      after freeze-thawing cycles the native form of JBU with apparent hydrodynamic
      radius of 7 nm and radius of gyration of 12 nm is replaced by high-order
      oligomers and this aggregation is not reverted neither by dithiothreitol (DTT)
      treatment nor by high concentration of salts. Altogether the data help to
      understand the complex behavior of JBU in solution and may correlate with the
      diversity of biological properties of this enzyme.

PMID- 15450379
TI  - Ultrasonic and dielectric study of nonequilibrium monosaccharide solutions in
      water.
AB  - Based on broadband acoustical (10 kHz < or = nu < or = 2 GHz) and dielectric (1
      MHz < or = nu < or = 40 GHz) spectrometry, time-resolved ultrasonic attenuation
      coefficient and static permittivity measurements have been performed on
      nonequilibrium tautomer solutions of d-arabinose and d-fructose in water. Via the
      chair-chair ring inversion the ultrasonic attenuation measurements display the
      decrease in the content of beta-arabinopyranoside and the increase of the alpha
      fructopyranoside concentration during the establishment of the tautomer
      equilibrium. For the arabinose solutions, the mutarotation decay constant
      (m=(0.027+/-0.004) min(-1), 20 degrees C) from the ultrasonic measurements almost
      agrees with that from optical activity observations. For d-fructose the
      ultrasonic decay constant (m=(0.043+/-0.007) min(-1), 20 degrees C) is smaller
      than that from rotary polarization (m=0.054 min(-1), 20 degrees C) and dielectric
      permittivity (m=(0.058+/-0.007) min(-1), 20 degrees C), likely because the latter
      methods probe parallel pathways in the tautomer equilibrium whereas the former
      one reflects only one pathway.

PMID- 15450380
TI  - Introduction: Is viral shedding a surrogate marker for transmission of genital
      herpes?
AB  - Genital herpes, caused by either herpes simplex virus type 1 or 2 (HSV-1 and HSV
      2), is a significant public health problem worldwide. It increases the risk of
      infection with HIV, upregulates HIV after infection and can be associated with
      serious morbidity and mortality. It is now known that clinical and subclinical
      viral reactivation with resultant shedding from anogenital mucosa occurs
      frequently, resulting in transmission during sexual contact. Sexual transmission
      of HSV infection is common, even between monogamous individuals. Antiviral
      therapy reduces the frequency and degree of viral shedding and lowers the
      transmission rate in discordant monogamous couples, although transmission can
      still occur in people prescribed antiviral therapy. These encouraging data raise
      important questions for the management of genital HSV infection, particularly
      with regard to the prevention of transmission. Although the quantity of virus
      present is clearly important in transmission of some viruses, it is not clear
      whether this is the case for HSV transmission. Ideally, a surrogate marker needs
      to be able to identify individuals with detectable amounts of virus, and
      differentiate them from individuals with detectable amounts of virus that are
      transmissible. The aim of this supplement is to explore the issues surrounding
      the validation of surrogate markers of transmission of HSV, using examples from
      other human viral diseases, and to review the available evidence. In the future,
      exploration of these issues may shed light on management and prevention
      strategies. In particular, the results may clarify what evidence is required to
      warrant prescribing a drug for reducing HSV transmission, and for which patient
      populations this strategy is appropriate.

PMID- 15450381
TI  - Lessons from HIV and hepatitis viruses.
AB  - Surrogate markers are an important component in the process of investigating
      management and prevention strategies, and for increasing understanding of viral
      diseases. The importance of surrogate markers and applied statistical models is
      particularly true for HIV. For HIV infection, the development of such methods
      provides new approaches for evaluation of HIV therapies and vaccines, and for the
      study of HIV transmission and its pathogenesis. The complex natural history of
      hepatitis B infection demonstrates that viral load is not the only predictor of
      transmission of this virus; for hepatitis C infection, viral load per se is not a
      prognostic factor for disease progression, but cumulative viral load may affect
      the outcome, and therapy is aimed at eliminating active viral replication.

PMID- 15450382
TI  - HSV shedding.
AB  - Viral shedding of HSV occurs frequently in infected individuals. HSV is shed
      asymptomatically from multiple anatomical sites and shedding, like exposure, is a
      significant risk for transmission. However, the relationship between shedding
      frequency, viral titer and transmission is unknown. HSV-2 shedding is affected by
      the site and time since acquisition of infection. The advent of sensitive PCR
      techniques has shown that the magnitude and frequency of viral shedding is higher
      than shown previously with viral culture techniques. It has also clearly
      demonstrated that suppressive (daily) antiviral therapy reduces clinical and
      subclinical reactivation rates, and has been successfully used in the prevention
      of recurrent oral and genital HSV infections. A recent study has demonstrated
      that daily antiviral therapy with valaciclovir can significantly reduce
      transmission of HSV-2 between discordant heterosexual couples in monogamous
      relationships.

PMID- 15450383
TI  - HSV-2 transmission.
AB  - A number of important risk factors for the acquisition of HSV-2 have been
      established including female gender, black or Hispanic ethnic origin, HIV
      infection, age, and increased number of sexual partners. Transmission is
      influenced by a number of biological factors such as sexual behavior, use of
      condoms, duration of relationships, and knowledge of a partner's serologic
      status. Vertical transmission (transmission of HSV from mother to neonate) is
      potentially life-threatening; neonatal HSV infection is associated with
      significant morbidity and mortality. The valaciclovir transmission study provides
      evidence that an antiviral agent can interrupt the transmission of a viral
      sexually transmitted disease between serologically discordant sexual partners.
      This review explores the importance of the cofactors that affect transmission,
      and makes recommendations on considerations for the prophylactic use of antiviral
      agents for the prevention of transmission in other patient populations.

PMID- 15450384
TI  - The role of human endogenous retroviruses in trophoblast differentiation and
      placental development.
AB  - A major portion of the human genome appears to be of retroviral origin. These
      endogenous retroviral elements are expressed in a variety of normal tissues and
      during disease states, such as autoimmune and malignant conditions. Recently,
      potential roles have been described for endogenous retroviral envelope proteins
      in normal differentiation of human villous cytotrophoblast into
      syncytiotrophoblast. This article provides a brief critical review of the current
      state of knowledge concerning the expression of the env regions of three
      endogenous retroviral elements: ERV-3, HERV-W, and HERV-FRD. A testable model of
      villous cytotrophoblast differentiation is constructed, in which a complementary
      expression of endogenous retroviral envelope proteins initiates hCG production,
      decreased cell proliferation, and intercellular fusion.

PMID- 15450385
TI  - Differential display RT-PCR analysis of human choriocarcinoma cell lines and
      normal term trophoblast cells: identification of new genes expressed in placenta.
AB  - In this study, we performed the differential display technique to identify genes
      specifically expressed in human choriocarcinoma cell lines (JEG-3, JAR and BeWo)
      and normal placental term cells. Few differences were found among the expression
      profiles of the three choriocarcinoma cell lines and most of the differentially
      expressed genes were detected in normal term placenta. A total of 36 cDNA
      fragments were isolated and analysed. Of these, 19 sequences corresponded to
      regions in the human genome coding for potential novel genes. We confirmed by RT
      PCR, the placental mRNA expression of three selected new human genes, on
      chromosomes 16q12, 9q32 and 6q22. The other 17 sequences showed high similarity
      to known human genes (like PSG3, FN1, PAI-2). Interestingly, the functions of
      five known proteins (from genes IK, TRA-1, HERPUD1, UBA-2, and TRAP240) have not
      yet been well characterized in placenta tissue. In addition, new alternative
      spliced mRNAs were detected for IK, TRAP240 and PLAC3 genes. The differential
      expression of the PAI-2 gene among the choriocarcinoma cell lines was also
      confirmed. The genes identified in this analysis will be of interest for future
      studies regarding both a better understanding of the biology of the trophoblast
      cell and the formation of placental tumors.

PMID- 15450386
TI  - Running throughout pregnancy: effect on placental villous vascular volume and
      cell proliferation.
AB  - Many studies have documented that placental development is altered by a variety
      of environmental factors which alter placental bed blood flow and/or oxygen
      delivery. One of these is sustained weight-bearing exercise. The purpose of this
      investigation was to examine the effects of running throughout pregnancy on
      villous vascular development and cell proliferation by testing the null
      hypothesis that continuing a regular running regimen throughout pregnancy has no
      effect on villous vascular volume or cell proliferation at term. Accordingly,
      placentae of 11 healthy runners with uncomplicated pregnancies were matched by
      placental weight, maternal diet and birth weight with those of 11 healthy
      controls and examined using systematic random sampling and point counting of
      placental tissues stained immunohistochemically with either an endothelial (CD
      31, PECAM-1, endoCam) or a proliferative (Ki-67, MIB-1) marker. The placentae of
      the runners had greater villous vascular volumes in both absolute (77 +/- 20
      cm(3) versus 47 +/- 18 cm(3), p < 0.02) and relative (% of total villous volume:
      29 +/- 5% versus 20 +/- 6%, p < 0.003) terms. Likewise, they had a greater
      proliferation index (45 +/- 14 mitoses/1000 nuclei versus 29 +/- 10 mitoses/1000
      nuclei, p < 0.008). We conclude that continuing to run regularly throughout
      pregnancy increases both absolute and relative villous vascular volume and cell
      proliferation at term. We also speculate that this exercise effect may have
      clinical value in cases at risk for anomalous feto-placental growth as increased
      villous vascular volume should improve feto-placental growth by enhancing
      placental transfer of oxygen and diffusible substrate.

PMID- 15450387
TI  - Effect of nuclear factor-kappa B inhibitors and peroxisome proliferator-activated
      receptor-gamma ligands on PTHrP release from human fetal membranes.
AB  - Parathyroid hormone-related protein (PTHrP) has been implicated in many processes
      during normal and pathological pregnancies. In the human fetal membranes, PTHrP
      exhibits cytokine-like actions. We have recently shown that inhibitors of the
      nuclear factor-kappa B (NF-kappaB) and activators of the peroxisome proliferator
      activated receptor (PPAR)-gamma signalling pathways down-regulate cytokine
      release from human gestational tissues. Therefore, the aim of this study was to
      determine whether NF-kappaB and PPAR-gamma also regulate PTHrP release from human
      fetal membranes. Human amnion and choriodecidua explants were incubated in the
      absence (control) or presence of two known NF-kappaB inhibitors (1, 5 and 10 mM
      sulphasalazine (SASP) or 5, 10 and 15 mM N-acetyl-cysteine (NAC)), and two PPAR
      gamma ligands (15 and 30 microM 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)) or 15
      and 30 microM troglitazone), under basal conditions. After 18 h incubation, the
      tissues were collected and NF-kappaB p65 DNA binding activity in nuclear extracts
      was assessed by ELISA, and the incubation medium was collected and the release of
      PTHrP was quantified by RIA. Treatment of amnion and choriodecidual tissues with
      SASP concentrations greater than 5 mM, 15 mM NAC, 30 microM 15d-PGJ(2) and 30
      microM troglitazone significantly reduced the release of PTHrP (p < 0.05). This
      study demonstrates that PTHrP release from human fetal membranes is regulated by
      inhibitors of NF-kappaB, and ligands of PPAR-gamma.

PMID- 15450388
TI  - Anatomical and histological characterization of the female reproductive organs of
      mouse deer (Tragulidae).
AB  - The Tragulidae may be a type that represents the earliest ruminant families to
      evolve. The female reproductive organs including ovary, oviduct, uterus and
      placenta were anatomically and histologically investigated. The structures of the
      ovary and oviduct were very similar to other ruminants. However, the gross
      structure of the placenta was diffuse and thus noticeably different from other
      ruminants which are polycotyledonary. Histologically, the placenta of Tragulidae
      appears to be epitheliochorial and therefore similar to other ruminants. Numerous
      trophoblastic binucleated cells which are characteristic of all other ruminants
      were observed. These results suggest that the placenta of Tragulidae is a
      transitional type between diffuse epitheliochorial and polycotyledonary
      synepitheliochorial categories.

PMID- 15450389
TI  - Leptin receptor expression increases in placenta, but not hypothalamus, during
      gestation in Mus musculus and Myotis lucifugus.
AB  - In addition to effects on appetite and metabolism, the hormone leptin is required
      for reproduction in mammals. Maternal plasma leptin is increased above non
      pregnant levels in all mammals thus far examined, including humans. The increase
      in plasma leptin appears to result in part from upregulation of adipose leptin
      secretion (e.g., in mice), or from production and secretion of leptin from the
      placenta (e.g., in humans and some bats). The placenta may also modulate maternal
      leptin levels via production of a plasma leptin-binding protein (mice, humans).
      Thus, the placenta plays a coordinating role in regulation of maternal leptin
      during pregnancy. In this study, the hypothesis that the placenta is also a
      target organ for leptin in diverse taxa was tested by examining the expression of
      leptin receptors (Ob-R) in placentae from species of distantly related mammalian
      taxa, Mus musculus (the laboratory mouse) and Myotis lucifugus (the little brown
      myotis, also called the little brown bat). A partial sequence of M. lucifugus Ob
      R cDNA was first obtained and found to share approximately 78-88% homology at the
      nucleotide level with known mammalian Ob-R cDNAs. Using probes and primers
      designed from this sequence, receptor expression was detected in numerous tissues
      of M. lucifugus, including placenta, which expressed two major receptor isoforms
      as judged by molecular size. In both species, Ob-R mRNA expression in placenta
      significantly increased from early to late gestation. Expression of Ob-R mRNA was
      not affected by cAMP treatment in vitro. The increase in Ob-R mRNA expression in
      placenta was specific, since Ob-R mRNA expression did not change during gestation
      in either species in hypothalamus, the major site of the central actions of
      leptin. Thus, Ob-R is expressed in placenta throughout gestation in mice and
      bats, and its expression increases over the course of gestation, which raises the
      possibility that leptin may exert temporally distinct effects on placental growth
      or function throughout gestation. Because similar placenta-specific changes in
      leptin receptor expression occurred in species from distantly related mammalian
      taxa which collectively comprise approximately 70% of all known mammalian
      species, it is possible that placental actions of leptin are conserved across
      mammals, even in those species (such as the Swiss-Webster strain of mouse) in
      which the placenta does not itself produce leptin.

PMID- 15450390
TI  - Non-selective cationic channels (NSCC) in smooth muscle cells from human
      umbilical arteries.
AB  - The aim of our work was to investigate the presence of non-selective cation
      channels (NSCC) in freshly isolated smooth muscle cells from the human umbilical
      artery (HUA), one of the vessels involved in fetal-placental circulation. We
      studied the electrophysiological properties of NSCC using the patch-clamp
      technique in whole-cell configuration, and their possible role in the contractile
      state of intact vessels' rings. Recording with a high intracellular Cs(+)
      solution and a near physiological extracellular saline solution, we found a
      Gd(3+)-sensitive current (IC(50) = 1.05 microM) with a linear current-voltage
      relationship showing a reversal potential (E(rev)) of -2.1 +/- 1.2 mV (n =15
      cells). La(3+) (100 microM) and Mg(2+) (5 mM) also blocked this current. In such
      conditions, inward currents were carried by Na(+) and Ca(2+); hence, a Na(+)-free
      solution inhibited only inward current (-67.3 +/- 11.4%, at -40 mV, n = 7, p <
      0.05) and a Ca(2+)-Na(+)-free solution decreased the current even further with
      respect to values obtained in Na(+)-free solution (-69.8 +/- 8.8% at -40 mV, n =
      9, p < 0.05). The permeability ratios (P(X)/P(Cs(+))) for monovalent and divalent
      cations were 1, 0.9, 0.7, 0.7, 0.7, and 0.5 where X = Cs(+), Na(+), Li(+),
      Ca(2+), Ba(2+) and Tris(+), respectively. In intact tissue, a 0 Ca(2+)
      extracellular solution, Gd(3+) (100-250 microM), La(3+) (200 microM) and Mg(2+)
      (5 mM) induced vasorelaxation in non-stimulated HUA rings.

PMID- 15450391
TI  - M385T polymorphism in the factor V gene, but not Leiden mutation, is associated
      with placental abruption in Finnish women.
AB  - This study determines whether genetic variability in the gene encoding factor V
      contributes to differences in susceptibility to placental abruption. Allele and
      genotype frequencies of three single nucleotide polymorphisms (SNPs) in the
      factor V gene leading to nonsynonymous changes (M385T in exon 8, and R485K and
      R506Q [Leiden mutation] in exon 10) were studied in 116 Caucasian women with
      placental abruption and 112 healthy controls. Single-point analysis was expanded
      to haplotype analysis and haplotype frequencies were estimated using an
      expectation-maximisation (EM) algorithm. Comparison of single-point allele and
      genotype distributions of SNPs in exon 8 and exon 10 of the factor V gene
      revealed statistically significant differences in M385T allele (P = 0.021) and
      genotype ( P = 0.013) frequencies between the patients and the control subjects.
      The C allele of SNP M385T was significantly less frequent among the patients (7%)
      vs. the control subjects (13%), at an odds ratio of 0.48 (95% CI 0.25-0.91).
      Allele and genotype differences between the patients and control subjects as
      regards R485K and Leiden mutation were not significant. In haplotype estimation
      analysis, there was a significantly lower frequency of haplotype T-R-R encoding
      the T385-R485-R506 variant in the group with placental abruption vs. the control
      group (P = 0.038) at an odds ratio of 0.519 (95% CI 0.272-0.987). We conclude
      that T385 is less frequent among the patient group than in the control group. The
      M385T variant in the factor V gene other than the Leiden mutation may play a role
      in disease susceptibility.

PMID- 15450392
TI  - Prognostic value of placental ultrasound in pregnancies complicated by absent end
      diastolic flow velocity in the umbilical arteries.
AB  - Our objective was to evaluate the utility of gray-scale placental ultrasound for
      the detection of pathological lesions in the placentas of preterm pregnancies
      with abnormal fetoplacental blood flow (defined by absent or reversed end
      diastolic flow velocities [ARED] in the umbilical arteries) before 32 weeks of
      gestation. Sixty consecutive structurally and chromosomally normal singleton
      pregnancies were evaluated. Pre-defined criteria were used to describe placental
      appearances using gray-scale real-time ultrasound. Proximal uterine artery
      Doppler waveforms were recorded using pulsed and color Doppler ultrasound. Each
      patient had a thrombophilia profile. Following delivery, a single perinatal
      pathologist reviewed each placenta at a gross and microscopic level blinded to
      the placental ultrasound findings. Placental shape or texture was abnormal on
      gray-scale ultrasound in 43/59 (73%) and echogenic cystic lesions (ECL) were
      found in 16 (27%). Uterine artery Doppler was abnormal in 47/60 (78%) cases.
      Thirty-eight pregnancies were subsequently delivered by planned Caesarean section
      in the fetal and/or maternal interest (birthweights 540-2300 g, mean gestational
      age 30.6 weeks) and 21 pregnancies resulted in the vaginal delivery of a
      stillborn fetus where fetal weight and/or gestational age did not justify
      Caesarean section (birthweights 85-600 g, mean gestational age 24.9 weeks). ECL
      had a low positive predictive value for both villous infarcts (63%) and for
      focal/massive perivillous fibrin deposition (40%). Nevertheless, the combination
      of abnormal uterine artery Doppler and abnormal gray-scale findings (abnormal
      placental morphology or ECL) was strongly predictive of stillbirth (17/21;
      sensitivity 81%, PPV 52%, p = 0.006 Fisher's exact test). Pregnancies with ARED
      in the umbilical arteries have a high perinatal mortality associated with
      pathology of the placental villi. Ultrasound examination of the placenta and its
      maternal blood supply may contribute to the perinatal management of these
      pregnancies.

PMID- 15450393
TI  - Pseudo-arterio-arterial anastomoses in twin-twin transfusion syndrome.
AB  - OBJECTIVE: It has recently been claimed that fetoscopic recognition of a
      haemodynamic equator within an arterio-arterial anastomosis (AAA) suggests
      minimal net intertwin flow. This was based on blood from one fetus being dark and
      from the other bright red, the boundary between them reciprocating with the fetal
      heart beats. However, bright red indicates that the blood had passed through a
      cotyledon and been freshly oxygenated, which should be impossible in an AAA. We
      applied a computer model of chorionic vessels to determine a configuration that
      reproduced this phenomenon. METHODS: A previously published TTTS model was
      extended to provide placental detail in a segment containing four cotyledons of
      each placenta supplied by three generations of placental arteries and veins.
      RESULTS: Reciprocating flow is not unique to AAAs. It also occurs in the
      chorionic arteries of any cotyledon deprived of its venous outflow, in a similar
      manner to that in which reverse end-diastolic flow occurs in umbilical arteries
      when whole placental resistance is high. If venous return from the common
      chorionic vein in the recipient (draining the venous end of an AVA) is blocked as
      might happen after laser, there can be bidirectional flow from one umbilical
      artery insertion, through two cotyledons to the other insertion. We define this
      phenomenon as a pseudo-AAA (PAAA). The inclusion of two cotyledons in this path
      means that its resistance cannot match the low flow resistance of a true AAA, and
      transmission of the contralateral pulsatile pattern is absorbed in the
      cotyledons. Thus, PAAA Doppler patterns differ from true AAA patterns in that two
      sets of systolic peaks, one forward and one reverse, can be discerned in true
      AAAs but only one in PAAAs. CONCLUSIONS: We demonstrate how venous occlusion of
      an arterio-venous anastomosis may produce a pseudo-AAA colour equator at
      endoscopy. However, visual observation of reciprocating flow is not sufficient to
      define a vessel as a true AAA which instead requires ultrasonical identification
      of two systolic patterns.

PMID- 15450396
TI  - Fetal growth restriction: a workshop report.
AB  - Intrauterine growth restriction (IUGR) is associated with significantly increased
      perinatal morbidity and mortality as well as cardiovascular disease and glucose
      intolerance in adult life. A number of disorders from genetic to metabolic,
      vascular, coagulative, autoimmune, as well as infectious, can influence fetal
      growth by damaging the placenta, leading to IUGR as a result of many possible
      fetal, placental and maternal disorders. Strict definitions of IUGR and of its
      severity are needed in order to eventually distinguish among different
      phenotypes, such as gestational age at onset, degree of growth restriction and
      presence of hypoxia. This report explores and reviews some of the most recent
      developments in both clinical and basic research on intrauterine growth
      restriction, by seeking mechanisms that involve genetic factors, utero-placental
      nutrient availability and vascular growth factors. New exciting findings on the
      genomic imprinting defects potentially associated with IUGR, and the placental
      anomalies associated with the decreased nutrient transport are summarized.
      Moreover, recent data on angiogenic growth factors as well as new information
      arising from application of gene chip technologies are discussed.

PMID- 15450397
TI  - The use of laser capture microdissection (LCM) and quantitative polymerase chain
      reaction to define thyroid hormone receptor expression in human 'term' placenta.
AB  - Term 'villous' placenta consists of a heterogeneous mix of different cell types
      comprising the trophoblast layers, villous stroma and fetal blood vessels. The
      importance of using techniques which allow investigation of pure populations of
      cells has been increasingly recognised. We demonstrate the use of laser capture
      microdissection (LCM) in combination with quantitative RT-PCR (QPCR) to assess
      the relative expression of mRNAs encoding the major thyroid hormone receptor (TR)
      isoforms (alpha1, alpha2 and beta1) in trophoblasts (syncytiotrophoblast and
      cytotrophoblast layers) compared with stromal cells in human term placenta.
      Highly reproducible results for each gene were obtained for each placental sample
      studied (n = 6). There was significantly less mRNA encoding TRalpha1 (68%; p =
      0.05) and TRbeta1 (40%; p = 0.03) in the trophoblast layer compared to the
      heterogeneous stromal cells. However, there was no significant difference in
      TRalpha2 mRNA expression between the two groups of cells. CONCLUSION: LCM with
      QPCR can precisely locate and accurately quantify mRNA expression in specific
      cell populations from placental tissue.

PMID- 15450398
TI  - Detection of incomplete chromosome elements and interstitial fragments induced by
      bleomycin in hamster cells using a telomeric PNA probe.
AB  - The detection of incomplete chromosome elements (ICE, i.e., elements with
      telomeric signal at only one terminal end) and interstitial fragments induced by
      the radiomimetic compound bleomycin (BLM) was carried out in a Chinese hamster
      embryo (CHE) cell line using FISH with a telomeric peptide nucleic acid (PNA)
      probe. CHE cells were treated with 0, 1, 2.5, 5, and 7.5 microg/ml of BLM and
      chromosomal aberrations were analyzed in the first mitosis after treatment using
      a telomeric PNA probe. The relationship between chromosomal aberrations frequency
      and bleomycin concentration was of linear type (P < 0.05 for all type of
      aberrations analyzed, i.e., multicentric chromosomes, centric rings, interstitial
      fragments and ICE). After BLM treatment, about 20-30% of the analyzed metaphases
      contained one or more pairs of ICE. Acentric interstitial fragments, lacking
      telomeric signals, were observed with a frequency of about 4-7 times higher than
      the dicentric frequency. Acentric interstitial fragments and ICE were induced at
      similar frequencies, except for the lowest BLM concentration (1 microg/ml), where
      the latter ones showed a higher frequency than the former ones. Furthermore, it
      was estimated that about 53% of excess acentric fragments originate from complete
      exchanges (interstitial deletions) and 47% from incomplete exchanges or terminal
      deletions. These results show that interstitial fragments and ICE are the most
      frequent asymmetrical chromosomal aberrations induced by BLM and indicate that
      true incompleteness is a common event following exposure to BLM. Moreover, the
      comparable trend of the concentration-response relationship for the different
      aberrations strongly suggests that all BLM-induced asymmetrical aberrations are
      formed by a similar underlying mechanism.

PMID- 15450399
TI  - DNA repair in human fibroblasts, as reflected by host-cell reactivation of a
      transfected UV-irradiated luciferase gene, is not related to donor age.
AB  - The effect of donor age on the ability of mammalian cells to repair ultraviolet
      (UV)-induced DNA damage has been studied using several approaches, most recently
      via assays that measure the host-cell reactivation (HCR) of UV-irradiated
      reporter gene-containing plasmid vectors following their transfection into cells.
      Plasmid HCR assays indirectly quantify a cell line's ability to perform
      nucleotide excision repair (NER) by measuring the enzyme activity of the repaired
      reporter gene, e.g., chloramphenical acetyltransferase (cat) or luciferase (luc),
      and are useful in studies investigating whether increasing age may be a risk
      factor for the deficient repair of potentially cancer-causing, sunlight-induced,
      DNA lesions in skin cells. In our study, we quantified the DNA repair ability of
      cultured, nontransformed, human skin fibroblast lines through their HCR of a
      transfected UV-C-irradiated plasmid containing luc. HCR was measured at various
      times after transfection in five lines from normal donors of ages 21-96 years,
      and from one donor who had xeroderma pigmentosum (XP). The normal lines displayed
      increasing HCR at successive post-transfection time points and showed no
      significant correlation between HCR and donor age. The XP-A line, known to be
      markedly deficient in NER of UV-induced DNA damage, showed minimal evidence of
      HCR compared to the normal lines. To further assess potential variation in HCR
      with donor age, fibroblast lines from five old donors, ages 84-94 years, were
      compared with lines from five young donors, ages 17-26 years. While significant
      differences in HCR were found between some lines, no significant difference was
      found between the young and old age groups (P = 0.44). Our study provides no
      indication that the higher incidence of skin cancer observed with increasing age
      is due to an age-related decrease in the ability to repair UV-induced DNA damage.

PMID- 15450400
TI  - A novel insertion mutation in the FOXL2 gene is detected in a big Chinese family
      with blepharophimosis-ptosis-epicanthus inversus.
AB  - Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES), an autosomal
      dominant syndrome in which an eyelid malformation is associated (type I) or not
      (type II) with premature ovarian failure (POF), has recently been ascribed to
      mutations in the forkhead transcription factor 2 (FOXL2) gene. In this work, we
      reveal a novel insertion mutation in the 3'UTR of the FOXL2 gene in a big Chinese
      family which is to our knowledge the first BPES (type II) family reported in
      China. It is the first time that a 3'UTR mutation in the FOXL2 gene has ever been
      found to demonstrate a close correlation between genotype and BPES. Our result
      gains a greater insight into the function of 3'UTR in the FOXL2 gene.

PMID- 15450401
TI  - Hypermethylation of the DNA repair gene MGMT: association with TP53 G:C to A:T
      transitions in a series of 469 nervous system tumors.
AB  - O6-methylguanine-DNA methyltransferase (MGMT) plays a major role in repairing DNA
      damage from alkylating agents. By removing alkyl groups from the O6-position in
      guanine, MGMT can prevent G:C to A:T transition mutations, a type of variation
      frequently involving TP53 mutations in brain tumors. Promoter hypermethylation of
      CpG islands in tumor-related genes can lead to their transcriptional
      inactivation, and this epigenetic mechanism has been shown to participate in MGMT
      silencing in some cancers, including those affecting the nervous system.
      Accordingly, a link between both genetic and epigenetic anomalies may exist in
      these neoplasms. To determine the relevance of defective MGMT function due to
      aberrant methylation in relation to the presence of TP53 mutations, we studied
      469 nervous system tumors (including all major histological subtypes) for MGMT
      promoter methylation and TP53 mutations at exons 5-8. Overall, aberrant
      methylation occurred in 38% of the samples (180/469), with values higher than 50%
      in the more malignant forms such as glioblastomas and anaplastic gliomas
      including those with astrocytic, oligodendroglial and ependymal differentiation.
      In contrast, the non-glial tumors displayed an overall aberrant MGMT promoter
      methylation of 26%, even though this group includes highly malignant tumors such
      as neuroblastomas, medulloblastomas and brain metastases. Overall, TP53 mutations
      were found in 25% of the methylated MGMT tumors (45/180), whereas only 10% of the
      unmethylated MGMT tumors (30/289) showed TP53 changes (P < 0.001). G:C to A:T
      changes occurred at CpG sites in 9% of methylated tumors, and in 0.7% of the
      unmethylated samples. This type of transition at non-CpG dinucleotides was also
      more frequent in the tumors with aberrant MGMT methylation (5%) than the
      unmethylated tumors (0.7%). These data suggest that MGMT silencing as a result of
      promoter hypermethylation may lead to G:C to A:T transition mutations in the TP53
      gene of some histological nervous system tumor subtypes.

PMID- 15450402
TI  - Genoprotective pathways. II. Attenuation of oxidative DNA damage by isopentenyl
      diphosphate.
AB  - Oxidative stress is believed to play a role in the pathogenesis of many diseases.
      Here we report that isopentenyl diphosphate (IPP), the 5-carbon building unit of
      all isoprenoids, is a potent antioxidant that is capable of inhibiting oxidative
      DNA damage at picomolar concentrations (IC50 = 1.7 x 10(-11) M). The diphosphate
      moiety is essential, since isopentenyl monophosphate (IMP) is unable to trigger
      antioxidative signaling. The 20-carbon isoprenyl, geranylgeranyl diphosphate
      (GGPP), but not the 15-carbon farnesyl diphosphate, displays similar
      genoprotective effects. The pathway activated by IPP is distinct from that of 2
      chloroadenosine (2CA). 2CA-mediated genoprotective signaling is transduced
      through an A2a or A2b adenosine receptor (AR) and can be blocked by the cyclic
      AMP (cAMP)-dependent protein kinase (PKA) inhibitor, H-89. In contrast, IPP
      signaling is independent of A2aAR, A2bAR, cAMP or PKA. Unlike the 2CA-mediated
      pathway, the effect of IPP is dependent on the mevalonate pathway, a
      geranylgeranylated protein and on intact proteasome activity. Thus, IPP is a
      potent activator of a novel genoprotective pathway. These findings shed new light
      on the role of isoprenoids in oxidative stress biology and may help to develop
      novel preventive strategies against oxidative damage.

PMID- 15450403
TI  - Ethnic variation in the prevalence of AZF deletions in testicular cancer.
AB  - Seventy-six percent of testicular cancers of origin in Finns have been reported
      to exhibit AZF deletions. We analyze here 40 testicular tumor cases from Norway
      and Argentina and we found that AZF deletions occur also in non-Finnish cases but
      at significantly lower frequency (25%) than in Finland testicular tumor cases.
      This frequency difference can be attributed to the condition of genetic isolate
      of the Finnish population and the subsequent prevalence in this ethnic group of
      genetic factors involved in the origin of AZF deletions associated with
      malignancies. The finding of a correlation between AZF deletions and a given Y
      haplogroup would indicate the existence of Y lineages carrying AZF deletion
      enhancing gene or genes. This possibility was explored using a set of Y-DNA
      markers allowing the identification of Y lineages occurring at high frequency in
      Finns. We characterized the Y haplogroups in 32 normal Finn males (control group)
      and 17 cases of testicular cancer in Finns with and without AZF deletions. We
      found no association between Y lineages and AZF microdeletions, nor between AZF
      microdeletions and a Y microdeletion (DYS7C) exhibiting high prevalence (>50%) in
      Finns. The lack of correlation between AZF deletions and Y haplogroups indicates
      that the origin of these deletions is independent from the Y chromosome genetic
      background. No AZF deletions were found in familial cases of testicular tumors;
      hence, hereditary factors inducing the appearance of testicular malignancies in
      certain genealogies apparently do not increase the susceptibility to AZF
      deficiencies. AZF deletions are de novo events occurring in prezygotic or in post
      zygotic stages. We propose that most AZF deletions associated with testicular
      tumors are due to post-zygotic Y microdeletions, while most cases of deletions
      associated with infertility are due to deletions occurring in the germ cell line
      of proband fathers.

PMID- 15450404
TI  - In vitro chemopreventive activity of Camellia sinensis, Ilex paraguariensis and
      Ardisia compressa tea extracts and selected polyphenols.
AB  - Several herbal teas contain bioactive compounds that have been associated with a
      lower risk of chronic diseases including cancer. The aim of this study was to
      evaluate the chemopreventive activity of tea aqueous extracts and selected
      constituent pure polyphenols using a battery of in vitro marker systems relevant
      for the prevention of cancer. The effects of (-) epigallocatechin gallate (EGCG),
      quercetin (Q), gallic acid (GA), green tea (GT, Camellia sinensis), ardisia tea
      (AT, Ardisia compressa) and mate tea (MT, Ilex paraguariensis) extracts were
      tested. Cytotoxicity, TPA-induced ornithine decarboxylase (ODC) and quinone
      reductase (QR) activities were evaluated in vitro using HepG2 cells. The
      topoisomerase inhibitory activity was also tested, using the Saccharomyces
      cerevisiae yeast system. Results suggest that MT, AT and GT are cytotoxic to the
      HepG2 cells, with MT demonstrating dominant cytotoxicity. EGCG showed greater
      cytotoxicity than Q and GA against HepG2 cells. The greatest inhibition (82%) of
      TPA-induced ODC activity was shown by Q, with 25 microM (IC50 = 11.90 microM).
      Topoisomerase II, but not topoisomerase I, was the cellular target of MT, AT,
      EGCG, Q and GA, which acted mainly as true catalytic inhibitors. The cytotoxic
      activity and the inhibition of topoisomerase II may contribute to the overall
      chemopreventive activity of AT and MT extracts. Ardisia and mate teas may thus
      share a public health potential as chemopreventive agents.

PMID- 15450405
TI  - Requirement of HSM3 gene for spontaneous mutagenesis in Saccharomyces cerevisiae.
AB  - In this work, we studied the influence of hsm3 mutation on spontaneous
      mutagenesis in actively and slowly dividing cells. We demonstrated that the
      spontaneous mutation rates in the hsm3 mutant and the wild type strain were
      similar in actively dividing cells. However, during 15-day cultivation of both
      strains we observed higher accumulation of mutants in the hsm3 strain compared
      with those in the wild type cells. Effect of accumulation of spontaneous mutants
      was observed in slowly dividing cells in the rad1, rad2, rad14, rad54, and pms1,
      but it was absent in the rev3, pol2 and pol3 mutants. Combinations of the hsm3
      mutation with the pol3-01, pol2-04 and pms1Delta mutations decreased
      significantly the level of spontaneous mutagenesis in rapidly growing cells. The
      hsm3 mutation suppressed synthetic lethality in the hsm3 pol3-01 pms1 triple
      mutant and dramatically increased the spontaneous mutation rate in comparison
      with double mutant. The introduction of the hsm3 mutation in NER-mutants led to
      considerably increasing of the spontaneous mutation level. The double hsm3 rev3,
      hsm3 rad54 and hsm3 pms1Delta mutants showed lower spontaneous mutation rate
      compared with the single mutants in rapidly dividing cells. The combination the
      hsm3 mutation with all studied mutations characterized by different degree of
      increase of spontaneous mutagenesis in slowly dividing cells. The participation
      of the Hsm3p in spontaneous mutagenesis in slowly and activity dividing yeast
      cells is discussed.

PMID- 15450406
TI  - Microarray-based AMASE as a novel approach for mutation detection.
AB  - Alterations in the p53 tumor suppressor gene are important events in many cases
      of human cancers. We have developed a novel microarray based approach for re
      sequencing and mutation detection of the p53 gene. The method facilitates rapid
      and simple scanning of the target gene sequence and could be expanded to include
      other candidate cancer genes. The methodology employs the previously described
      apyrase-mediated allele-specific extension reaction (AMASE). In order to re
      sequence the selected region, four extension oligonucleotides with different 3'
      termini were used for each base position and they were covalently attached to the
      glass slide's surface. The amplified single-stranded DNA templates were then
      hybridized to the array followed by in situ extension with fluorescently labeled
      dNTPs in the presence of apyrase. The model system used was based on analysis of
      a 15 bp stretch in exon 5 of the p53 gene. Mutations were scored as allelic
      fractions calculated as (wt)/(wt + mut) signals. When apyrase was included in the
      extension reactions of wild type templates, the mean allelic fraction was 0.96.
      When apyrase was excluded with the same wild type templates, significantly lower
      allelic fractions were obtained. Two 60-mer synthetic oligonucleotides were used
      to establish the detectable amount of mutations with AMASE and a clear
      distinction between all the points could be made. Several samples from different
      stages of skin malignancies were also analyzed. The results from this study imply
      the possibility to efficiently and accurately re-sequence the entire p53 gene
      with AMASE technology.

PMID- 15450407
TI  - Micronuclei with multiple copies of the X chromosome: do chromosomes replicate in
      micronuclei?
AB  - The formation of a micronucleus due to chromosome lagging is a well known
      mechanism of chromosomal loss. However, the post-mitotic fate of the micronucleus
      and the chromosomal DNA within it is poorly understood. We observed micronuclei
      (MN) that had multiple copies of the X chromosome (ranging from 4 to 10) when
      analyzing cultured human lymphocytes using fluorescence in situ hybridization
      (FISH). A possible mechanism for this observation is that the chromosome(s) or
      chromatid(s) contained within the micronuclei successfully completed one or more
      cycles of replication after their expulsion from the primary nucleus.

PMID- 15450408
TI  - Genetic recombination destabilizes (CTG)n.(CAG)n repeats in E. coli.
AB  - The expansion of trinucleotide repeats has been implicated in 17 neurological
      diseases to date. Factors leading to the instability of trinucleotide repeat
      sequences have thus been an area of intense interest. Certain genes involved in
      mismatch repair, recombination, nucleotide excision repair, and replication
      influence the instability of trinucleotide repeats in both Escherichia coli and
      yeast. Using a genetic assay for repeat deletion in E. coli, the effect of
      mutations in the recA, recB, and lexA genes on the rate of deletion of
      (CTG)n.(CAG)n repeats of varying lengths were examined. The results indicate that
      mutations in recA and recB, which decrease the rate of recombination, had a
      stabilizing effect on (CAG)n.(CTG)n repeats decreasing the high rates of deletion
      seen in recombination proficient cells. Thus, recombination proficiency
      correlates with high rates of genetic instability in triplet repeats. Induction
      of the SOS system, however, did not appear to play a significant role in repeat
      instability, nor did the presence of triplet repeats in cells turn on the SOS
      response. A model is suggested where deletion during exponential growth may
      result from attempts to restart replication when paused at triplet repeats.

PMID- 15450409
TI  - The mutagenic effects of 7,12-dimethylbenz[a]anthacene, 3-methylcholanthrene and
      benzo[a]pyrene to the developing Syrian hamster fetus measured by an in vivo/in
      vitro mutation assay.
AB  - The transplacental mutagenicity of three polycylic aromatic hydrocarbons, 7,12
      dimethylbenz[a]anthacene (DMBA), 3-methylcholanthrene (MC) and benzo[a]pyrene
      (BP), was measured by an in vivo/in vitro mutation assay. Fetal sensitivity and
      dose-response characteristics with regard to transplacental mutagenesis by these
      compounds have never been quantified. In the current experiment, pregnant Syrian
      hamsters were exposed to these compounds at day 12 of gestation. Twenty-four
      hours later the fetuses were removed and their cells were allowed a 5-day
      expression time in culture. They were then seeded for colony formation and also
      for mutation selection by diphtheria toxin. DMBA at 0.2 mmol/kg (51.3 mg/kg) had
      an induced mutant frequency of 1.56 x 10(-4) mutants per surviving cell. This was
      598 times the historical control. DMBA at 0.2 mmol/kg was 3.6 times more potent
      than the highly mutagenic positive control, ethylnitrosourea, at 1 mmol/kg. DMBA
      also caused a dose-dependent increase in cloning efficiency, which was highly
      correlated with mutation rate. BP and MC were less effective than DMBA, causing
      increased mutations that were 31.6 and 17.7 times the historical control,
      respectively, and for neither was there any correlation of mutation rate with
      cloning efficiency. The special effectiveness of DMBA as a transplacental mutagen
      may relate to its ability to cause increased cell division and fixation of DNA
      lesions as mutations.

PMID- 15450410
TI  - Induction of apoptosis by benzamide and its inhibition by aurin tricarboxylic
      acid (ATA) in Chinese hamster V79 cells.
AB  - To investigate the effect of benzamide and nicotinamide, well known inhibitors of
      poly(ADP-ribose) polymerase, in Chinese hamster V79 cells at the physiological
      condition of cell growth, we have tested the ability of the inhibitors to induce
      apoptosis. Apoptosis was detected by nuclear fragmentation, nucleosomal ladder
      formation, cytochrome-c release from the mitochondria and caspase-3 activation.
      Benzamide treatment alone increased nuclear fragmentation in dose (2.5-10 mM) and
      time (4-48 h)-dependent manner. Such treatment also increased nucleosomal
      ladders. However, 5 mM benzamide pre-treatment inhibited the nucleosomal ladders
      induced by gamma-irradiation indicating the role of poly(ADP-ribose) polymerase
      was different in irradiated cells and in un-irradiated cells. Release of
      cytochrome-c from the mitochondria and caspase-3 activity were also increased by
      such treatment. Treatment with 200 microM of aurin tricarboxylic acid (ATA), an
      inhibitor of DNases, inhibited the nucleosomal ladders induced by benzamide or
      gamma-irradiation without changing the cytochrome-c release or caspase-3
      activation. This result showed that ATA inhibited the nucleosomal ladders
      possibly by inhibiting DNase(s) involved in apoptosis.

PMID- 15450411
TI  - Spontaneous and induced chromosomal damage and mutations in Bloom Syndrome mice.
AB  - Bloom Syndrome (BS) is characterized by both cancer and genomic instability,
      including chromosomal aberrations, sister chromosome exchanges, and mutations.
      Since BS heterozygotes are much more frequent than homozygotes, the issue of the
      sensitivity of heterozygotes to cancer is an important one. This and many other
      questions concerning the effects of BLM (the gene responsible for the BS) are
      more easily studied in mice than in humans. To gain insight into genomic
      instability associated with loss of function of BLM, which codes for a DNA
      helicase, we compared frequencies of micronuclei, somatic mutations, and loss of
      heterozygosity (LOH) in Blmtm3Brd homozygous, heterozygous, and wild-type mice
      carrying a cII transgenic reporter gene. It should be noted that the Blmtm3Brd is
      inserted into the endogenous locus with a partial duplication of the gene, so
      some function of the locus may be retained. The cII reporter gene was introduced
      from the Big Blue mouse by crossing them with Blmtm3Brd mice. All measurements
      were made on F2 mice from this cross. The reticulocytes of Blmtm3Brd homozygous
      mice had more micronuclei than heterozygous or wild-type mice (4.5, 2.7, and 2.5
      per thousand, respectively; P < 0.01) but heterozygotes did not differ
      significantly from wild-type. Unlike spontaneous chromosome damage, spontaneous
      mutant frequencies did not differ significantly among homozygous, heterozygous,
      and wild-type mice (3.2 x 10(-5), 3.1 x 10(-5), and 3.1 x 10(-5), respectively; P
      > 0.05). Mutation measurements were also made on mice that had been treated with
      ethyl-nitrosourea (ENU) because Bloom Syndrome cells are sensitive to ethylating
      agents. The ENU-induced mutation frequency in Blmtm3Brd homozygous, heterozygous,
      and wild mice were 54 x 10(-5), 35 x 10(-5), and 25 x 10(-5) mutants/plaques,
      respectively. ENU induced more mutations in Blmtm3Brd homozygous mice than in
      wild-type mice (P < 0.01), but not significantly more in heterozygous mice (P =
      0.06). Spontaneous LOH did not differ significantly among the genotypes, but ENU
      treatment induced much more LOH in Blmtm3Brd homozygous mice, as measured by
      means of the Dlb-1 test of Vomiero-Highton and Heddle. Hence, these Blmtm3Brd
      mice resemble Bloom Syndrome except that they have normal frequencies of
      spontaneous mutation. The fact that these mice have elevated rates of both cancer
      and chromosomal aberrations (as shown by more micronuclei and LOH) but normal
      rates of spontaneous mutation, shows the greater importance of chromosomal events
      than mutations in the origin of their cancers.

PMID- 15450412
TI  - Basal, oxidative and alkylative DNA damage, DNA repair efficacy and mutagen
      sensitivity in breast cancer.
AB  - Impaired DNA repair may fuel up malignant transformation of breast cells due to
      the accumulation of spontaneous mutations in target genes and increasing
      susceptibility to exogenous carcinogens. Moreover, the effectiveness of DNA
      repair may contribute to failure of chemotherapy and resistance of breast cancer
      cells to drugs and radiation. The breast cancer susceptibility genes BRCA1 and
      BRCA2 are involved in DNA repair. To evaluate further the role of DNA repair in
      breast cancer we determined: (1) the kinetics of removal of DNA damage induced by
      hydrogen peroxide and the anticancer drug doxorubicin, and (2) the level of
      basal, oxidative and alkylative DNA damage before and during/after chemotherapy
      in the peripheral blood lymphocytes of breast cancer patients and healthy
      individuals. The level of DNA damage and the kinetics of DNA repair were
      evaluated by alkaline single cell gel electrophoresis (comet assay). Oxidative
      and alkylative DNA damage were assayed with the use of DNA repair enzymes
      endonuclease III (Endo III) and formamidopyrimidine-DNA glycosylase (Fpg),
      recognizing oxidized DNA bases and 3-methyladenine-DNA glycosylase II (AlkA)
      recognizing alkylated bases. We observed slower kinetics of DNA repair after
      treatment with hydrogen peroxide and doxorubicin in lymphocytes of breast cancer
      patients compared to control individuals. The level of basal, oxidative and
      alkylative DNA damage was higher in breast cancer patients than in the control
      and the difference was more pronounced when patients after chemotherapy were
      engaged, but usually the level of DNA damage in these patients was too high to be
      measured with our system. Our results indicate that peripheral blood lymphocytes
      of breast cancer patients have more damaged DNA and display decreased DNA repair
      efficacy. Therefore, these features can be considered as risk markers for breast
      cancer, but the question whether they are the cause or a consequence of the
      illness remains open. Nevertheless, our results suggest that research on the
      mutagen sensitivity and efficacy of DNA repair could impact the development of
      new diagnostic and screening strategies as well as indicate new targets to
      prevent and cure cancer. Moreover, the comet assay may be applied to evaluate the
      suitability of a particular mode of chemotherapy to a particular cancer patient.

PMID- 15450413
TI  - RecN and RecG are required for Escherichia coli survival of Bleomycin-induced
      damage.
AB  - The sensitivity of a panel of DNA repair-defective bacterial strains to BLM was
      investigated. Escherichia coli recA cells were far more sensitive than were uvrA,
      dam-3, and mutM mutY strains, underscoring the importance of RecA to survival.
      Strains recBCD and recN, which lack proteins required for double strand break
      (DSB) repair, were highly sensitive to BLM, while recF cells were not. The
      requirement for DSB-specific enzymes supports the hypothesis that DSBs are the
      primary cause of bleomycin cytotoxicity. The acute sensitivity of recN cells was
      comparable to that of recA, implying a central role for the RecN protein in BLM
      lesion repair. The Holliday junction processing enzymes RecG and RuvC were both
      required for BLM survival. The recG ruvC double mutant was no more sensitive than
      either mutation alone, suggesting that both enzymes participate in the same
      pathway. Surprisingly, ruvAB cells were no more sensitive than wildtype, implying
      that RuvC is able to perform its role without RuvAB. This observation contrasts
      with current models of recombination in which RuvA, B, and C function as a single
      complex. The most straightforward explanation of these results is that DSB repair
      involves a structure that serves as a good substrate for RecG, and not RuvAB.

PMID- 15450414
TI  - Identification of a novel polymorphism in the fibronectin type II domain of the
      SEL1L gene and possible relation to the persistent hyperinsulinemic hypoglycemia
      of infancy.
AB  - SEL1L, a human gene located on chromosome 14q24.3-q31, is highly expressed in
      adult pancreas. It is proximal to D14S67 (IDDM11) a proposed type I diabetes
      susceptibility locus. Considering the organ specific expression of SEL1L, a
      fundamental role of SEL1L in pancreatic growth can be hypothesized. While
      screening for mutations in young diabetic patients, in children affected by
      persistent hyperinsulinemic hypoglycemia of infancy (PHHI), in patients with non
      functional endocrine tumours and in over 100 control subjects, we identified a
      novel polymorphism (D162G) residing on the fourth exon of the gene. This exon
      encodes for the fibronectin type II domain and the nucleotide change involves a
      highly conserved amino acid. The D162G polymorphism induces a major change in the
      amino acid composition producing a possible disruptive role in collagen binding.

PMID- 15450415
TI  - Inhibitory effects of water-soluble cationic manganese porphyrins on
      peroxynitrite-induced SOS response in Salmonella typhimurium TA4107/pSK1002.
AB  - We have investigated the protective effects of water-soluble cationic Mn(III)
      porphyrins against peroxynitrite (ONOO-)-induced DNA damage in the cells of
      Salmonella typhimurium TA4107/pSK1002 and lipid peroxidation of red blood cell
      membranes. Mn(III) tetrakis (N-methylpyridinium-4-yl) porphine (TMPyP) and the
      brominated form, Mn(III) octabromo-tetrakis (N-methylpyridinium-4-yl) porphine
      (OBTMPyP) effectively reduced the damage and peroxidation induced by N-morpholino
      sydnonimine (SIN-1), which gradually generates ONOO- from O2*- and *NO produced
      through hydrolysis. Mn(III)OBTMPyP became 10-fold more active than the non
      brominated form. In the presence of authentic ONOO-, the Mn(III) porphyrins were
      ineffective against damage and strongly enhanced lipid peroxidation, while the
      coexistence of ascorbic acid inhibited peroxidation. Using a diode array
      spectrophotometry, the reactions of Mn(III)TMPyP with authentic ONOO- and SIN-1
      were measured. Mn(III)TMPyP is known to be catalytic for ONOO- decomposition in
      the presence of antioxidants. OxoMn(IV)TMPyP with SIN-1 was rapidly reduced back
      to Mn(III) without adding any oxidants. Further, in the SIN-1 system, the
      concentration of NO2- and NO3- were colorimetrically determined by Griess
      reaction based on the two-step diazotization. NO2- increased by addition of
      Mn(III) porphyrin and the ratio of NO2- to NO3- was 4-7 times higher than that
      (1.05) of SIN-1 alone. This result suggests that O2*- from SIN-1 acts as a
      reductant and *NO cogenerated is oxidized to NO2-, a primarily decomposition
      product of *NO. Under the pathological conditions where biological antioxidants
      are depleted and ONOO- and O2*- are extensively generated, the Mn(III) porphyrins
      will effectively cycle ONOO- decomposition using O2*-.

PMID- 15450416
TI  - Missense mutations in cancer suppressor gene TP53 are colocalized with exonic
      splicing enhancers (ESEs).
AB  - Mutation databases can be viewed as footprints of functional organization of a
      gene and thus can be used to infer its functional organization. We studied the
      association of exonic splicing enhancers (ESEs) with missense mutations in the
      tumor suppressor gene TP53 using the International Agency for Research on Cancer
      (IARC) mutation database. The goals of the study were: (i) to verify the
      hypothesis that deleterious missense mutations are colocalized with ESEs; (ii) to
      identify potentially functional ESE sites in the open reading frame (ORF) of the
      TP53. If some sequence functions as a splicing enhancer, then nucleotide
      substitutions in the site will disturb splicing, abrogate p53 function, and cause
      an increased susceptibility to cancer. Therefore, among cancers showing p53
      mutations, more missense mutations are expected within functional ESE sites as
      compared to non-functional ESE motifs. Using several statistical tests, we found
      that missense mutations in TP53 are strongly colocalized with ESEs, and that only
      a small fraction of ESE sites contributes to the association. There are usually
      one or two ESEs per exon showing a statistically significant association with
      missense mutations--so-called significant ESE sites. In many respects significant
      ESE sites are different from those that do not show association with missense
      mutations. We found that positions of significant ESE sites are codon-dependent-
      significant ESEs preferentially start from the first position of a codon, whereas
      non-significant ESEs show no position dependence. Significant ESEs showed a more
      limited set of sequences compared to non-significant ESEs. These findings suggest
      that there is a limited number of missense mutations that influence ESE sites and
      our analysis provides further insight into the types of sites that harbor exonic
      enhancer elements.

PMID- 15450417
TI  - Mutational spectrum of bleomycin in lacZ mouse kidney: a possible model for
      mutational spectrum of reactive oxygen species.
AB  - The mutational spectrum of bleomycin was compared with the spontaneous mutational
      spectrum in lacZ mouse kidney. Mice were treated with four 20 mg/kg of doses of
      bleomycin over a two-week period, leading to a mutant fraction several times
      greater than that of controls. The major class of bleomycin-induced mutations
      consisted of small deletions, in particular -1 deletions at AT base pairs and hot
      spots for deletions at 5'-GTC-3' sequences. Smaller, but significant fractions of
      GC > AT followed by GC > TA substitutions were also observed. In untreated mice,
      the major class of mutations consisted of GC > AT substitutions followed by GC >
      TA mutations, and a much smaller fraction of deletions. Other than the
      specificity of bleomycin for AT base pairs and the 5'-GTC-3' hotspots, the
      mutational spectrum of bleomycin in mice is similar to that reported for ionizing
      radiation. However, bleomycin initially mediates the formation of oxidized DNA
      via reduction of molecular oxygen, as opposed to the radiolysis of water. In this
      respect mutagenesis induced by bleomycin may be more similar to that induced by
      endogenous reactive oxygen species (ROS) than mutagenesis induced by ionizing
      radiation. If bleomycin-induced mutagenesis is an appropriate model for
      mutagenesis induced by ROS, then, based on the difference between the mutational
      spectrum of bleomycin and spontaneous mutagenesis, the latter appears not to
      result predominantly from ROS, at least in mouse kidney.

PMID- 15450418
TI  - Positive selection for loss of RpoS function in Escherichia coli.
AB  - Though RpoS, an alternative sigma factor, is required for survival and adaptation
      of Escherichia coli under stress conditions, many strains have acquired
      independent mutations in the rpoS gene. The reasons for this apparent selective
      loss and the nature of the selective agent are not well understood. In this
      study, we found that some wild type strains grow poorly in succinate minimal
      media compared with isogenic strains carrying defined RpoS null mutations. Using
      an rpoS+ strain harboring an operon lacZ fusion to the highly-RpoS dependent osmY
      promoter as an indicator strain, we tested if this differential growth
      characteristic could be used to selectively isolate mutants that have lost RpoS
      function. All isolated (Suc+) mutants exhibited attenuated beta-galactosidase
      expression on indicator media suggesting a loss in either RpoS or osmY promoter
      function. Because all Suc+ mutants were also defective in catalase activity, an
      OsmY-independent, RpoS-regulated function, it was likely that RpoS activity was
      affected. To confirm this, we sequenced PCR-amplified products containing the
      rpoS gene from 20 independent mutants using chromosomal DNA as a template.
      Sequencing and alignment analyses confirmed that all isolated mutants possessed
      mutated alleles of the rpoS gene. Types of mutations detected included single or
      multiple base deletions, insertions, and transversions. No transition mutations
      were identified. All identified point mutations could, under selection for
      restoration of beta-galactosidase, revert to rpoS+. Revertible mutation of the
      rpoS gene can thus function as a genetic switch that controls expression of the
      regulon at the population level. These results may also help to explain why
      independent laboratory strains have acquired mutations in this important
      regulatory gene.

PMID- 15450419
TI  - A mixture of isothiocyanates induces cyclin B1- and p53-mediated cell-cycle
      arrest and apoptosis of human T lymphoblastoid cells.
AB  - As with other candidate chemopreventive agents, most of our knowledge on the
      biological effects of isothiocyanates (the many sulfur-containing metabolites
      found in cruciferous vegetables) comes from studies of single natural or
      synthetic compounds. To investigate whether the biological/chemopreventive
      effects of administration of single isothiocyanates can differ from those of a
      mixture of isothiocyanates, we tested the effects of a mixture of four different
      isothiocyanates on cell-cycle progression and apoptosis in human T leukemia
      Jurkat cells, and identified some of the molecular pathways triggered by the
      mixture. The mixture affected critical points of the cell cycle via modulation of
      the expression of cyclin B1. Moreover, it induced apoptosis, mediated by an
      increase in p53 and bax (expression of bcl-2 was unaffected). Comparison of the
      data with those previously obtained with the single isothiocyanates under
      identical experimental conditions provides evidence that the quantitative effects
      of a single, specific isothiocyanate can be significantly different from those of
      an isothiocyanate mixture at realistic doses.

PMID- 15450420
TI  - Overexpression of p16INK4a correlates with high expression of p73 in breast
      carcinomas.
AB  - The p16-cyclin D-Cdk4(6)-pRB-E2F and p73 pathways are involved in the control of
      cell-cycle progression, and genetic lesions in both pathways frequently occur in
      breast carcinomas and other human cancers. The p16INK4a gene is involved in
      regulation of the G1/S transition, and when overexpressed, the p73 gene activates
      transcription of p53-responsive genes and promotes apoptosis. These pathways are
      related, for instance, p73 is also downstream of E2F-1, since E2F-1 induces p73
      mediated apoptosis in the absence of p53. We studied 93 breast cancer patients to
      identify alterations in the expression of p16INK4a and p73 by semiquantitative RT
      PCR analysis and possible interactions between them and correlations with
      clinicopathological parameters. p73 was overexpressed in 24 cases. Overexpression
      of p16INK4a was detected in 17 cases and underexpression in 32 cases. A
      significant correlation was observed between the overexpression of both genes (P
      = 0.05). Concurrent overexpression of p73 and p16INK4a was significantly
      correlated with metastases in three or more lymph nodes (P = 0.0007), positive
      immunohistochemistry for p53 (P = 0.014), vascular invasion (P = 0.048) and
      negative progesterone receptors (P = 0.004). These results indicate that
      concomitant overexpression of p16INK4a and p73 may be involved in breast cancer
      and associated with poor tumor characteristics.

PMID- 15450421
TI  - Spontaneous multiple mutations show both proximal spacing consistent with
      chronocoordinate events and alterations with p53-deficiency.
AB  - Analysis of spontaneous multiple mutations in normal and tumor cells may
      constrain hypotheses about the mechanisms responsible for multiple mutations and
      provide insight into the mutator phenotype. In a previous study, spontaneous
      doublets in Big Blue mice were dramatically more frequent than expected by chance
      and exhibited a mutation pattern similar to that observed for single mutations
      [Mutat. Res. 452 (2000) 219]. The spacing between mutations in doublets was
      generally closer than expected by chance and the distribution of mutation spacing
      fit an exponential, albeit with substantial scatter. We now analyze 2658
      additional mutants and confirm that doublets are enhanced dramatically relative
      to chance expectation. The spacing, frequency and pattern of spontaneous doublets
      and multiplets (domuplets) are examined as a function of age, tissue type, p53
      deficiency and neoplasia in the new and combined data. The new and combined data
      confirm that the distribution of the spacing between mutations in doublets is non
      random with the mutations more closely spaced than expected by chance (P <
      0.0005; combined data), consistent with temporally coordinate (chronocoordinate)
      events. An exponential provides an excellent fit to the distribution (R2 = 0.98)
      and estimates that half of doublets have mutations separated by 120 nucleotides
      or less (the "half-life of mutation spacing"). We make several novel
      observations: (i) singlets and doublets show similar overall increases in
      frequency with age (ii) doublet frequency may be lower in the male germline,
      consistent with the generally reduced mutation frequency in the male germline
      (iii) doublet frequencies are elevated in somatic tissues of p53-deficient mice
      (Li-Fraumini cancer syndrome model; P = 0.005) and (iv) doublets and singlets in
      tumors from p53-deficient mice have a different mutation pattern (P = 0.007). The
      observations are consistent with chronocoordinate occurrence of spontaneous
      doublets and multiplets due to a transient error-prone condition and do not
      suggest a major role for the recently discovered Y family of error-prone
      polymerases. The enhancement of doublets in p53-deficient mice may contribute to
      cancer risk.

PMID- 15450422
TI  - The ATM-SMC1 pathway is essential for activation of the chromium[VI]-induced S
      phase checkpoint.
AB  - Hexavalent chromium (Cr[VI]) is a common industrial waste product, an
      environmental pollutant, and a recognized human carcinogen. Following cellular
      uptake, Cr[VI] can cause DNA damage, however, the mechanisms by which mammalian
      cells respond to Cr-induced DNA damage remain to be elucidated. Using single cell
      gel electrophoresis (e.g., Comet Assay) and immunofluoresence microscopy to
      detect the presence of gamma-H2AX foci, we find that Cr[VI] induces DNA double
      strand breaks similar to ionizing radiation (IR). We also demonstrated that
      ataxia telangiectasia mutated (ATM) is activated in response to Cr[VI] and
      exposure to Cr[VI] triggers a dose and ATM-dependent S-phase arrest. Further, we
      document that ATM is required for phosphorylation of the structural maintenance
      of chromosome protein 1 (SMC1). Finally, we find that ATM-dependent
      phosphorylation of SMC1 is required to facilitate S-phase cell-cycle arrest in
      response to Cr[VI] exposure. Collectively, these results indicate that the ATM
      SMC1 pathway plays a critical role in cellular response to Cr[VI].

PMID- 15450423
TI  - A genotoxic screen: rapid analysis of cellular dose-response to a wide range of
      agents that either damage DNA or alter genome maintenance pathways.
AB  - SNP analysis has come to the forefront of genomics since the mouse and human
      genomes have been sequenced. High throughput functional screens are necessary to
      evaluate these sequence databases. Described here is a genotoxic screen: a rapid
      method that determines the cellular dose-response to a wide range of agents that
      either damage DNA or alter basic cellular pathways important for maintaining
      genomic integrity. Importantly, a single person utilizing standard tissue culture
      equipment may perform these assays composed of 20 agents that attack genomic
      integrity or maintenance at many different levels. Thus, a small lab may perform
      this screen to determine the integrity of a wide range of DNA repair, chromatin
      metabolism, and response pathways without the limitations of investigator bias. A
      genotoxic screen will be useful when analyzing cells with either known genetic
      alterations (generated directly by the investigator or derived from individuals
      with known mutations) or unknown genetic alterations (cells with spontaneous
      mutations such as cancer-derived cells). Screening many genotoxins at one time
      will aid in determining the biological importance of these altered genes. Here we
      show the dose-response curves of mouse embryonic stem (ES) cells and HeLa cells
      exposed to 20 genotoxic agents. ES cells were chosen since they are amenable to
      genetic alteration by the investigator. HeLa cells were chosen since they were
      derived from cancer and are commonly used. Comparing the dose-response curves of
      these two cell lines show their relative sensitivity to these agents and helps
      define their genotoxic profile. As a part of phenomics, a large genotoxic profile
      database for cancer-derived cells, when integrated with other databases such as
      expression profiles and comparative genomic hybridization, may aid in maximizing
      the effectiveness of developing anti-cancer protocols.

PMID- 15450424
TI  - Identification of genetic polymorphisms of CYP2S1 in a Finnish Caucasian
      population.
AB  - CYP2S1 is a recently discovered member of the cytochrome P450 (CYP) gene
      superfamily. Interestingly, even though the DNA sequence identifies it as the
      sole member of the new CYP2S family, CYP2S1 exhibits many features typical to
      CYP1 family members, e.g. dioxin-inducibility mediated by the aryl hydrocarbon
      receptor (AHR) and the aryl hydrocarbon receptor nuclear translocator (ARNT). In
      addition, CYP2S1 metabolises some aromatic hydrocarbons as well as cellular
      substances. These characteristics, together with a wide extrahepatic tissue
      distribution, suggest that CYP2S1 may have an important role in both exogenous
      and endogenous metabolism. This is the first study characterising CYP2S1 alleles
      and naming them with the recommended CYP allele nomenclature. We used denaturing
      gradient gel electrophoresis (DGGE) and direct sequencing to investigate genetic
      variation of CYP2S1 in 100 male Finnish Caucasians. Those exons in which
      variation was found were examined in subsequent 100 subjects. The coding region
      of all of the nine exons, as well as a 449 bp fragment of the proximal promoter
      region, was analysed. This systematic investigation revealed eight single
      nucleotide polymorphisms (SNPs), which comprise nine different variant alleles
      (haplotypes), in addition to the wild-type allele. Seven of the SNPs occurred in
      the protein-coding areas and one in the proximal 3' untranslated region (3'UTR).
      Two of these sequence variations (10347C > T and 13106C > T) result in non
      conservative amino acid substitutions, i.e. Arg380Cys and Pro466Leu,
      respectively. The respective allelic variants, CYP2S1*2 ([10347C > T]) and
      CYP2S1*3 (13106C > T; 13255A > G]), occurred in our study population at
      frequencies of 0.50 and 3.75%, respectively. The most common of the variant
      alleles was CYP2S1*1H (23.8%), harbouring a 13255A > G substitution located in
      the 3'UTR.

PMID- 15450425
TI  - Sucrose and IQ induced mutations in rat colon by independent mechanism.
AB  - Sucrose-rich diets have repeatedly been observed to have co-carcinogenic actions
      in colon and liver of rats and to increase the number of 2-amino-3
      methylimidazo[4,5-f]quinoline (IQ) induced aberrant crypt foci in rat colon. To
      investigate a possible interaction between sucrose and IQ on the genotoxicity in
      rat liver and colon, we gave Big Blue rats a diet containing sucrose (0%, 3.45%
      or 13.4% w/w) and/or IQ (70 ppm) for a period of 3 weeks. Sucrose and IQ
      increased the mutation frequency in the colon. The effect of combined treatments
      with IQ and sucrose on the mutation frequencies was additive indicating that
      sucrose and IQ act independently. This was supported by the mutation spectra
      where sucrose expands the background mutations in the colon, whereas IQ, in other
      studies, more specifically has induced G:C --> T:A transversions. In the liver IQ
      increased the mutation frequency, whereas addition of sucrose reduced the effect
      of IQ in a dose-dependent manner. The level of bulky DNA adducts in liver and
      colon was increased in animals exposed to either sucrose or IQ. In animals
      exposed to IQ, addition of sucrose had marginal effects on the level of bulky DNA
      adducts. Markers of oxidative damage and DNA repair were generally unaffected by
      the treatments. In conclusion, sucrose and IQ in the diet induced mutations in
      the colon by independent mechanisms, whereas an interaction was observed in liver
      leading to a decrease in mutations by the combined treatment.

PMID- 15450426
TI  - Germline mutation rates at tandem repeat loci in DNA-repair deficient mice.
AB  - Mutation rates at two expanded simple tandem repeat (ESTR) loci were studied in
      the germline of non-exposed and irradiated severe combined immunodeficient (scid)
      and poly(ADP-ribose) polymerase (PARP-1-/-) deficient male mice. Non-exposed scid
      and PARP-/- male mice showed considerably elevated ESTR mutation rates, far
      higher than those in wild-type isogenic mice and other inbred strains. The
      irradiated scid and PARP-1-/- male mice did not show any detectable increases in
      their mutation rate, whereas significant ESTR mutation induction was observed in
      the irradiated wild-type isogenic males. ESTR mutation spectra in the scid and
      PARP-1-/- strains did not differ from those in the isogenic wild-type strains.
      Considering these data and the results of previous studies, we propose that a
      delay in repair of DNA damage in scid and PARP-1-/- mice could result in
      replication fork pausing which, in turn, may affect ESTR mutation rate in the non
      irradiated males. The lack of mutation induction in irradiated scid and PARP-1-/-
      can be explained by the high cell killing effects of irradiation on the germline
      of deficient mice.

PMID- 15450427
TI  - DNA damage and repair in type 2 diabetes mellitus.
AB  - DNA damage may be associated with type 2 diabetes mellitus (T2DM) and its
      complications mainly through oxidative stress. Little is known about DNA repair
      disturbances potentially contributing to the overall extent of DNA damage in
      T2DM, which, in turn, may be linked with genomic instability resulting in cancer.
      To assess whether DNA repair may be perturbed in 2DM we determined: (1) the level
      of endogenous basal DNA damage, this means damage recognized in the alkaline
      comet assay (DNA strand breaks and alkali labile sites) as well as endogenous
      oxidative and alkylative DNA damage (2) the sensitivity to DNA-damaging agents
      hydrogen peroxide and doxorubicin and the efficacy of removing of DNA damage
      induced by these agents in peripheral blood lymphocytes of T2DM patients and
      healthy individuals. The level of DNA damage and the kinetics of DNA repair was
      evaluated by the alkaline single cell gel electrophoresis (comet assay).
      Oxidative and alkylative DNA damage were assayed with the use of DNA repair
      enzymes endonuclease III (Endo III) and formamidopyrimidine-DNA glycosylase
      (Fpg), recognizing oxidized DNA bases and 3-methyladenine-DNA glycosylase II
      (AlkA) recognizing alkylated bases. The levels of basal endogenous and oxidative
      DNA damage in diabetes patients were higher than in control subjects. There was
      no difference between the level of alkylative DNA in the patients and the
      controls. Diabetes patients displayed higher susceptibility to hydrogen peroxide
      and doxorubicin and decreased efficacy of repairing DNA damage induced by these
      agents than healthy controls. Our results suggest that type 2 diabetes mellitus
      may be associated not only with the elevated level of oxidative DNA damage but
      also with the increased susceptibility to mutagens and the decreased efficacy of
      DNA repair. These features may contribute to a link between diabetes and cancer
      and metrics of DNA damage and repair, measured by the comet assay, may be markers
      of risk of cancer in diabetes.

PMID- 15450428
TI  - Expression of hepatitis B virus X oncoprotein inhibits transcription-coupled
      nucleotide excision repair in human cells.
AB  - The hepatitis B virus X protein (HBx) is implicated in liver cancer development,
      and this presumably involves its ability to bind and functionally inactivate the
      p53 tumour suppressor. For example expression of HBx in cultured cells has been
      shown to inhibit global nucleotide excision repair, a p53-dependent subpathway of
      nucleotide excision repair (NER) which eliminates helix-distorting DNA adducts,
      e.g., UV-induced cyclobutane pyrimidine dimers (CPDs), from the genome overall.
      However it remains undetermined whether HBx also interferes with transcription
      coupled NER (TCNER), another NER subpathway which removes DNA adducts uniquely
      from the transcribed strand (TS) of active genes. To address this, we employed
      the model human lymphoblastoid strain TK6 and its isogenic p53-null counterpart
      NH32, in conjunction with derivatives of these strains constitutively expressing
      HBx (TK6-HBx and NH32-HBx). Relative to TK6, following exposure to either UVB
      (290-320 nm) or UVC (254 nm), TK6-HBx, NH32 and NH32-HBx manifested significantly
      reduced apoptotic capacity to varying degrees, although no striking differences
      in clonogenic survival between the four strains were observed. As previously
      documented in our laboratory [Proc. Natl. Acad. Sci. 100 (2003) 7219-7224],
      ligation-mediated PCR analysis revealed NH32 to be deficient compared with TK6 in
      CPD removal along the TS strand of the chromosomal c-jun locus following UVB
      exposure, but to be proficient in this respect following UVC exposure, i.e., the
      requirement for p53 in TCNER exhibits wavelength dependence in human cells.
      Remarkably however, in contrast to the situation for NH32, TK6-HBx and NH32-HBx
      manifested defective repair along the TS of c-jun after irradiation with either
      UVB or UVC. The data demonstrate that HBx expression can reduce the efficiency of
      TCNER in addition to GNER in human cells via p53-independent as well as p53
      dependent pathways.

PMID- 15450429
TI  - Genetic polymorphisms of DNA repair and xenobiotic-metabolizing enzymes: effects
      on levels of sister chromatid exchanges and chromosomal aberrations.
AB  - Elevated levels of chromosomal aberrations (CAs) in peripheral blood lymphocytes,
      widely used as a cytogenetic biomarker of genotoxic effects, have been linked to
      cancer predisposition. However, tobacco smoking, occupational carcinogen
      exposure, or time since CA analysis do not appear to explain the cancer
      predictivity of CAs. Alternatively, the observed CA-cancer association could
      reflect unidentified exposures or individual susceptibility. We assessed the
      effects of genetic polymorphisms of DNA repair proteins and xenobiotic
      metabolizing enzymes (XMEs) on the levels of CAs and sister chromatid exchanges
      (SCEs) in peripheral lymphocytes of 145 (CAs) and 60 (SCEs) healthy Caucasians.
      Genotypes of DNA repair genes X-ray repair cross-complementation group 1 (XRCC1
      codons 194, 280, 399) and 3 (XRCC3 codon 241 [corrected]), and XME genes
      glutathione-S-transferase (GST) M1 and T1 and N-acetyl transferase 2 (NAT2) were
      determined using polymerase chain reaction (PCR) and restriction fragment length
      polymorphism (RFLP)-based methods. After Poisson regression adjustment for age,
      sex, smoking, country, and genotypes, a higher frequency of chromosome-type
      breaks was observed for NAT2 slow acetylators (in nonsmokers) and GSTT1 null
      subjects (in smokers). Individuals carrying variant alleles for XRCC1 codons 280
      and 194 showed a decreased level of chromosome-type breaks. The effect of GSTM1
      null and XRCC1 codon 399 genotypes on the frequency of CAs was modified by
      smoking. In linear regression models adjusting for age, sex, smoking, and
      genotypes, none of the polymorphisms significantly affected SCE frequency,
      although GSTT1 null subjects had a slightly elevated SCE level. Our results are
      in line with earlier findings on the influence of NAT2, GSTT1, and GSTM1
      polymorphisms on the level of lymphocyte chromosome damage and suggest that also
      XRCC1 polymorphism affects CA frequencies, thus apparently influencing DNA repair
      phenotype. It remains to be examined whether these or other genetic polymorphisms
      could explain the observed cancer risk predictivity of high CA frequency.

PMID- 15450430
TI  - Comparative mutagenicity of halomethanes and halonitromethanes in Salmonella
      TA100: structure-activity analysis and mutation spectra.
AB  - Halonitromethanes (HNMs) are a recently identified class of disinfection by
      products (DPBs) in drinking water that are mutagenic in Salmonella and potent
      inducers of DNA strand breaks in mammalian cells. Here we compared the mutagenic
      potencies of the HNMs to those of their halomethane (HM) homologues by testing
      all nine HNMs and seven of the nine HMs (minus bromomethane and chloromethane)
      under the same conditions (the pre-incubation assay) in Salmonella TA100 +/- S9.
      We also determined the mutation spectra for several DBPs. In the presence of S9,
      all nine HNMs, but only three HMs, dibromomethane (DBM), dichloromethane (DCM),
      and bromochloromethane (BCM), were mutagenic. Only two DBPs of each class were
      mutagenic in the absence of S9. The HNMs were generally more potent mutagens than
      their HM homologues, and the brominated forms of both classes of DBPs were more
      mutagenic and cytotoxic than their chlorinated homologues. The HNMs were at least
      10 times more cytotoxic than the HMs, and the cytotoxicity rankings in the
      presence of S9 were similar for the HNMs and the HMs. The addition of a nitro
      group to BCM did not change the mutation spectra significantly, with both
      homologues inducing primarily (55-58%) GC --> AT transitions. The greater
      cytotoxic and mutagenic activities of the HNMs relative to the HMs are likely due
      to the greater intrinsic reactivity conferred by the nitro-group. Energy
      calculations predicted increased reactivity with increasing bromination and
      greater reactivity of the HNMs versus the HMs (Elumo values were approximately 20
      kcal/mol lower for the HNMs compared to their HM homologues). Given that the HNMs
      also are potent genotoxins in mammalian cells [Environ. Sci. Technol. 38 (2004)
      62] and are more mutagenic and 10x more cytotoxic in Salmonella than the HMs,
      whose levels are regulated in drinking water, further study of their occurrence
      and potential health effects is warranted.

PMID- 15450431
TI  - Effect of Ku86 and DNA-PKcs deficiency on non-homologous end-joining and
      homologous recombination using a transient transfection assay.
AB  - In mammalian cells, DNA double-strand breaks are repaired by non-homologous end
      joining and homologous recombination, both pathways being essential for the
      maintenance of genome integrity. We determined the effect of mutations in Ku86
      and DNA-PK on the efficiency and the accuracy of double-strand break repair by
      non-homologous end-joining and homologous recombination in mammalian cells. We
      used an assay, based on the transient transfection of a linearized plasmid DNA,
      designed to simultaneously detect transfection and recombination markers. In
      agreement with previous results non-homologous end-joining was largely
      compromised in Ku86 deficient cells, and returned to normal in the Ku86
      complemented isogenic cell line. In addition, analysis of DNA plasmids recovered
      from Ku86 mutant cells showed an increased use of microhomologies at the
      nonhomologous end joining junctions, and displayed a significantly higher
      frequency of DNA insertions compared to control cells. On the other hand, the DNA
      PKcs deficient cell lines showed efficient double-strand break repair by both
      mechanisms.

PMID- 15450432
TI  - Suppression of chemically induced and spontaneously occurring oxidative
      mutagenesis by three alleles of human OGG1 gene encoding 8-hydroxyguanine DNA
      glycosylase.
AB  - 8-Hydroxyguanine (8-OH-G) is an oxidatively damaged guanine base that causes G:C
      to T:A transversion mutations. To counteract the mutagenicity of 8-OH-G in DNA,
      humans possess the hOGG1 gene, which encodes 8-OH-G DNA glycosylase.
      Interestingly, genetic polymorphisms at codon 326 (hOGG1-Ser326 versus hOGG1
      Cys326) and at codon 46 (hOGG1-Arg46 versus hOGG1-Gln46) exist in human
      populations. hOGG1-Ser326 and -Cys326 have Arg at codon 46, and hOGG1-Gln46 has
      Ser at codon 326. In this study, we examined the abilities of three forms of GST
      hOGG1 (hOGG1-Ser326, -Cys326 and -Gln46) to suppress chemically induced oxidative
      mutagenesis using Salmonella typhimurium strains YG3001 and YG3002. These strains
      are the mutMST derivatives of Ames tester strains TA1535 (uvrB-) and TA1975
      (uvrB+), respectively. The mutMST gene encodes a functional counterpart of the
      OGG1 gene. Mutations induced by 4-nitroquinoline 1-oxide were by more than 95%
      suppressed by the expression of any of three forms of GST-hOGG1 in strain YG3002.
      Expression of GST-hOGG1 also reduced by 40 and 60%, respectively, the numbers of
      His+ revertants induced by methylene blue plus visible light and benzo[a]pyrene
      plus visible light in strain YG3001. hOGG1-Gln46 displayed a slightly weaker
      ability to suppress the mutations induced by methylene blue plus visible light
      than did other two forms although the differences were not statistically
      significant. About 85 and 95% of spontaneous mutagenesis in strain YG3021 and
      YG3022, the mutMST mutYST double mutants of strain TA1535 and TA1975,
      respectively, were suppressed by the expression of any of hOGG1 alleles. hOGG1
      Gln46 displayed a weaker suppression than did other two forms in strain YG3022
      and the difference was statistically significant. These results suggest that
      three alleles of the hOGG1 gene efficiently suppress chemically induced and
      spontaneously occurring oxidative mutagenesis, and that hOGG1-Gln46 may have a
      weaker ability to suppress the mutations.

PMID- 15450433
TI  - Cigarette smoke induces anaphase bridges and genomic imbalances in normal cells.
AB  - Exposure to cigarette smoke has long been linked to carcinogenesis, but the
      emphasis has been placed on mutational changes in the DNA sequence caused by the
      carcinogens in smoke. Here, we report an additional role for cigarette smoke
      exposure in contributing to chromosomal aberrations in cells. We have found that
      cigarette smoke condensate (CSC) induces anaphase bridges in cultured human
      cells, which in a short time lead to genomic imbalances. The frequency of the
      induced bridges within the entire population decreases with time, and this
      decrease is not dependent upon the p53-mediated apoptotic pathway. Additionally,
      we show that CSC induces DNA double stranded breaks (DSBs) in cultured cells and
      purified DNA. The reactive oxygen species (ROS) scavenger, 2' deoxyguanosine 5'
      monophosphate (dGMP) prevents CSC-induced DSBs, anaphase bridge formation and
      genomic imbalances. Therefore, we propose that CSC induces bridges and genomic
      imbalances via DNA DSBs. Furthermore, since the amount of CSC added to the
      cultures was substantially less than that extracted from a single cigarette, our
      results show that even low levels of cigarette smoke can cause irreversible
      changes in the chromosomal constitution of cultured cells.

PMID- 15450434
TI  - Comparison of the mutagenic activity of the benzene metabolites, hydroquinone and
      para-benzoquinone in the supF forward mutation assay: a role for minor DNA
      adducts formed from hydroquinone in benzene mutagenicity.
AB  - Benzene, a ubiquitous environmental pollutant and occupational hazardous
      chemical, is a recognised human leukaemogen and rodent carcinogen. The mechanism
      by which benzene exerts its carcinogenic effects is to date unknown but it is
      considered that mutations induced by benzene-DNA adducts may play a role. The
      benzene metabolite, para-benzoquinone (p-BQ) following reaction in vitro with
      DNA, forms four major adducts, which include two adducts on 2'-deoxyguanosine 3'
      monophosphate (dGp). Reaction of DNA with the benzene metabolite hydroquinone
      (HQ) results in only one major DNA adduct, which corresponds to one of the dGp
      adducts formed following reaction with p-BQ. The mutagenicity of the adducts
      formed from these two benzene metabolites was investigated using the supF forward
      mutation assay. Metabolite-treated plasmid (pSP189) containing the supF gene was
      replicated in human Ad293 cells before being screened in indicator bacteria.
      Treatment with 5-20 mM p-BQ gave a 12 to 40-fold increase in mutation rate
      compared to 5-20 mM HQ treatment, a result reflected in the level of DNA
      modification observed (8 to 26-fold increase compared to HQ treatment). Treatment
      with p-BQ gave equal numbers of GC --> TA transversions and GC --> AT
      transitions, whereas treatment with HQ gave predominantly GC-->AT transitions.
      The spectra of mutations achieved for the two individual treatments were shown to
      be significantly different (P = 0.004). A combination of both treatments also
      resulted in a high level of GC --> AT transitions and a synergistic increase in
      the number of multiple mutations, which again predominated as GC --> AT
      transitions. Sites of mutational hotspots were observed for both individual
      treatments and one mutational hotspot was observed in the multiple mutations for
      the combined treatment. These results suggest that the dGp adducts formed from
      benzene metabolite treatment may play an important role in the mutagenicity and
      myelotoxicity of benzene.

PMID- 15450435
TI  - Analysis of the involvement of human N-acetyltransferase 1 in the genotoxic
      activation of bladder carcinogenic arylamines using a SOS/umu assay system.
AB  - Human acetyltransferase genes NAT1 or NAT2 were expressed in a Salmonella
      typhimurium strain used to detect the genotoxicity of bladder carcinogens. To
      clarify whether the human and rodent bladder carcinogenic arylamines are
      activated via either NAT1 or NAT2 to cause genotoxicity, a SOS/umu genotoxicity
      assay was used, with the strains S. typhimurium NM6001 (NAT1-overexpressing
      strain), S. typhimurium NM6002 (NAT2-overexpressing strain), and S. typhimurium
      NM6000 (O-AT-deficient parent strain). Genotoxicity was measured by induction of
      SOS/umuC gene expression in the system, which contained both an umuC"lacZ fusion
      gene and NAT1 or NAT2 plasmids. 4-Aminobiphenyl, 2-acetylaminofluorene, beta
      naphthylamine, o-tolidine, o-anisidine, and benzidine exhibited dose-dependent
      induction of the umuC gene in strain NM6001. Although the induction of umuC by
      these chemicals was observed in the NM6002 strain, the induction was considerably
      lower than in the NM6001 strain. In the parent strain, NM6000, none of these
      compounds induced umuC gene expression. We also determined activation of these
      chemicals by recombinant human cytochrome P450 (P450 or CYP) 1A2 enzyme in three
      S. typhimurium tester strains. The activation of the chemicals was stronger in
      the NM6001 strain than that in NM6002. The specific NAT1 inhibitor 5
      iodosalicylic acid inhibited umuC gene expression induced by aromatic amines
      used. These results could provide evidence that the bladder carcinogenic aromatic
      amines are mainly activated by the NAT1 enzyme to produce DNA damage rather than
      NAT2. The NAT1-overexpressing strain can be used to determine the genotoxic
      activation of bladder carcinogenic arylamines in the umu test and could provide a
      tool for predicting the carcinogenic potential of arylamines.

PMID- 15450436
TI  - It is not just the poor kids: the use of AAE forms by African-American school
      aged children from middle SES communities.
AB  - This study examined the production of African-American English (AAE) forms
      produced by 69 school-aged African-American children from middle socio-economic
      status (SES) communities to determine if age would influence: (a) the number of
      different types of AAE tokens and (b) the rate of dialect. Descriptive data
      revealed that there were more than 20 AAE morpho-syntactic forms collectively
      used by the children. The findings also indicated that factors of age, gender,
      and sampling context interacted in a variety of ways to influence these
      children's production of the number of different types of AAE tokens, and the
      rate of dialect. LEARNING OUTCOMES: Readers should have (1) an increased
      awareness about the use of AAE forms in school-age children from middle SES
      homes; (2) a greater understanding of how the production of AAE might be
      influenced by age, gender, and sampling context.

PMID- 15450437
TI  - Descriptive discourse: topic familiarity and disfluencies.
AB  - This investigation was undertaken to address questions about topic familiarity
      and disfluencies during oral descriptive discourse of adult speakers.
      Participants expressed more attributes when the topic was familiar than when it
      was unfamiliar. Fillers and lexical pauses were the most frequent disfluencies.
      The mean duration of each hesitation pause was 776 ms. The sum of hesitation
      pause durations was well correlated with the number of occurrences. Repetitions,
      hesitation pauses, and prolongations were shown to have the same role, which was
      distinct from the role of fillers. The type of analysis conducted in this
      investigation may be useful in distinguishing between normal and disordered
      speech production. LEARNING OUTCOMES: The reader will obtain information about
      the differences between the number of propositions in familiar and unfamiliar
      oral descriptions. The reader will also become aware of the distribution of
      disfluencies in discourse categories employed by the participants in this
      investigation.

PMID- 15450438
TI  - Effects of noise and filtering on the intelligibility of speech produced during
      simultaneous communication.
AB  - This study investigated the effects of noise and filtering on the intelligibility
      of speech produced during simultaneous communication (SC). Four normal hearing,
      experienced sign language users were recorded under SC and speech alone (SA)
      conditions speaking Boothroyd's forced-choice phonetic contrast material designed
      for measurement of speech intelligibility. Twenty-four normal hearing listeners
      audited the speech samples produced by the four speakers under the SC and SA
      conditions, three listeners in noise and three listeners in filtered listening
      conditions for each of the four speakers. Although results indicated longer
      sentence durations for SC than SA, the data showed no difference in the
      intelligibility of speech produced during SC versus speech produced during SA
      under either the noise or filtered listening condition, nor any difference in
      pattern of phonetic contrast recognition errors between the SA and SC speech
      samples in either listening condition. This conclusion is consistent with
      previous research indicating that temporal alterations produced by SC do not
      produce degradation of temporal or spectral cues to speech intelligibility or
      disruption of the perception of specific English phoneme segments. LEARNING
      OUTCOMES: As a result of this activity, the participant will be able to (1)
      describe simultaneous communication; (2) explain the role of simultaneous
      communication in communication with children who are deaf; (3) discuss methods of
      measuring speech intelligibility under filtered and noise conditions; and (4)
      specify the ability of listeners to perceive speech produced during simultaneous
      communication under noise and filtered listening conditions.

PMID- 15450439
TI  - Complex syntax used by school-age children with specific language impairment
      (SLI) in child-adult conversation.
AB  - The present study is an investigation of complex sentence structures produced by
      school-age children in ordinary 100-utterance language samples. A total of 15
      children with specific language impairment (SLI) and 15 of their classmates with
      typical language (TL) were the participants. Each child's conversational sample
      was coded for several types of complex sentence structures. While a 100-utterance
      language sample was adequate to yield exemplars of several types of spoken
      syntactic complexity, findings raise concerns about the content validity of
      conversational language sampling in the assessment of spoken syntactic
      complexity. Results also indicated that, although the children with SLI produced
      fewer complex sentences as well as combined complex sentences than their
      classmates with TL, they produced some examples of most spoken complex sentence
      structures in their conversations. Implications for using conversational language
      sampling to assess complex syntax are discussed. LEARNING OUTCOMES: The reader
      will (a) explain the strengths and weaknesses of language sampling in assessment
      of spoken syntactic complexity in school-age children, and (b) describe
      differences in children with SLI and children with TL for spoken syntactic
      complexity in child-adult conversation, as well as how to account for those
      differences.

PMID- 15450440
TI  - Sign language iconicity and its influence on the ability to describe the function
      of objects.
AB  - We examined the influence of sign language iconicity on children's ability to
      describe the function of objects. Forty-eight hearing preschoolers were divided
      into three groups and asked to describe the function of 15 high and 15 low iconic
      signs. We questioned the Hearing/Verbal (H/V) group verbally, Hearing/Verbal +
      Sign (H/V+S) group verbally with objects simultaneously signed, and the
      Hearing/Sign (H/S) group with objects signed without voice. Ten deaf children
      (D/S) were also tested using sign language. H/S and D/S performed significantly
      better on high than low iconic items. Nine signs were sufficiently iconic to aid
      function identification by sign naive hearing children. Results suggest that
      certain highly iconic signs may contribute to performance on tests administered
      in sign language. LEARNING OUTCOMES: The reader will learn about sign language
      iconicity and its influence on the ability of hearing and deaf children to
      perform on object function questions.

PMID- 15450441
TI  - Ionic surfactant adsorption onto activated carbons.
AB  - The adsorption of sodium dodecyl sulfate onto a set of activated carbons from
      aqueous solutions has been studied in the low concentration range. The adsorption
      isotherms are reasonably well fitted by a double Langmuir equation but the
      calorimetry of adsorption enthalpies shows a rather wide distribution of
      energies. This distribution is related to direct adsorbate-adsorbent interactions
      in pores of different size, without noticeable contributions from the chemical
      nature of the surface. The adsorbate-adsorbent interaction free energy through
      water is evaluated using the model proposed by van Oss and co-workers for the
      interfacial free energy. The obtained results indicate that the calculated free
      energy is in good agreement with that found from application of the double
      Langmuir equation to the adsorption isotherms.

PMID- 15450442
TI  - Copper(II) adsorption on Ca-rectorite, and effect of static magnetic field on the
      adsorption.
AB  - Rectorite is a kind of rare clay mineral. In this work, the sorption of Cu(II) on
      Ca-rectorite and the effects of static magnetic fields on the sorption have been
      studied. The results from this study indicated that (1) apparent equilibrium for
      the sorption of copper onto Ca-rectorite is attained within the first hour; (2)
      magnetic treatment enhances the zeta potential of Ca-rectorite suspensions in the
      absence of Cu and reduces that of the suspension in the presence of Cu; (3)
      magnetic treatment promotes the sorption of Cu onto Ca-rectorite, especially at
      low Cu concentrations; (4) the effects of static magnetic fields decrease the pH
      of Ca-rectorite suspensions whether they contain copper or not. The effect
      mechanisms of static magnetic field on the sorption of Cu onto Ca-rectorite were
      discussed.

PMID- 15450443
TI  - Adsorption of arsenate and arsenite on titanium dioxide suspensions.
AB  - Adsorption of arsenate (As(V)) and arsenite (As(III)) to two commercially
      available titanium dioxide (TiO2) suspensions, Hombikat UV100 and Degussa P25,
      was investigated as a function of pH and initial concentration of adsorbate ions.
      The BET surface area and zeta potential values of TiO2 were also measured to
      understand the difference in adsorption behavior of two suspensions. Both As(V)
      and As(III) adsorb more onto Hombikat UV100 particles than Degussa P25 particles.
      Adsorption of As(V) onto TiO2 suspensions was more than As(III) at pH 4 while the
      adsorption capacity of As(III) was more at pH 9. The electrostatic factors
      between surface charge of TiO2 particles and arsenic species were used to explain
      adsorption behavior of As(V) and As(III) at different pH. The Langmuir and
      Freundlich isotherm equations were used to interpret the nature of adsorption of
      arsenic onto TiO2 suspensions. The usefulness of adsorption data in removing
      arsenic in water is briefly discussed.

PMID- 15450444
TI  - Influence of anodic treatment on heavy metal ion removal by activated carbon
      fibers.
AB  - In this work, the effect of electrochemical oxidation treatment on activated
      carbon fibers (ACFs) was studied in the context of Cr(VI), Cu(II), and Ni(II)
      adsorption behavior. Ten weight percent phosphoric acid (A-ACFs) and ammonia (B
      ACFs) were used for acidic and basic electrolytes, respectively. Surface
      properties of ACFs were determined by X-ray photoelectron spectroscopy (XPS). The
      specific surface area and the pore structure were evaluated from nitrogen
      adsorption data at 77 K. As a result, the electrochemical oxidation treatment led
      to an increase in the amount of oxygen-containing functional groups. Also, the
      adsorption capacity of the electrochemically oxidized ACFs was improved in the
      order B-ACFs > A-ACFs > untreated-ACFs, in spite of a decrease in specific
      surface area which resulted from pore blocking by functional groups and pore
      destruction by acidic electrolyte. It was clearly found that the heavy metal ions
      were largely influenced by the functional groups on the ACF surfaces.

PMID- 15450445
TI  - Surface complexation of carbonate on goethite: IR spectroscopy, structure and
      charge distribution.
AB  - The adsorption of carbonate on goethite has been evaluated, focussing on the
      relation between the structure of the surface complex and corresponding
      adsorption characteristics, like pH dependency and proton co-adsorption. The
      surface structure of adsorbed CO3(-2) has been assessed with (1) a
      reinterpretation of IR spectroscopy data, (2) determination of the charge
      distribution within the carbonate complex using surface complexation modeling,
      and (3) evaluation of the proton co-adsorption of various oxyanions, including
      carbonate, in relation with structural differences. Carbonate adsorption leads to
      a degeneration of the nu3 IR vibration. Currently, the magnitude of the Deltanu3
      band splitting is used as a criterion for metal coordination. However, the
      interpretation is not unambiguous, since the magnitude of Deltanu3 is influenced
      by polarization and additional field effects, due to, e.g., H bonding. Our
      evaluation shows that for goethite the magnitude of band splitting Deltanu3 falls
      within the range of values that is representative for bidentate complex
      formation, despite contrarily assignments made in literature. Determination of
      the charge distribution (CD), derived by modeling available carbonate adsorption
      data, shows that a very large part (2/3) of the carbonate charge resides in the
      surface. Interpretation of this result with a bond valence and a ligand charge
      analysis strongly favors the bidentate surface complexation option for adsorbed
      carbonate. This option is also supported by the proton co-adsorption of
      carbonate. The H co-adsorption is very high, which corresponds closely to an
      oxyanion surface complex in which 2/3 of the ligands are common with the surface.
      The high H co-adsorption is in conflict with the monodentate option for adsorbed
      CO3(-2). The study shows that the H co-adsorption of CO3(-2) is almost equal to
      the experimental H co-adsorption obtained for SeO3(-2) adsorption, which can be
      rationalized supposing for both XO3(-2) complexes the same ligand distribution in
      the interface, i.e., bidentate complex formation.

PMID- 15450446
TI  - Cd(II) binding by particulate low-rank coals in aqueous media: sorption
      characteristics and NICA-Donnan models.
AB  - An experimental investigation of Cd(II) sorption onto two Australian coals was
      carried out in 0.1 M NaNO3 at 298.2 K. The initial concentration of Cd(II) was
      varied from 0.133 to 2.000 mmol/g in a series of batch adsorption experiments
      with an initial coal concentration of 3.75 g/L of Loy Yang (brown) or of Collie
      (sub-bituminous) coals in the p[H+] range 2-8. Adsorption edges were typical of
      metal ion adsorption onto negatively charged organic substrates, starting at
      p[H+] approximately 3 and increasing with increasing pH. The largest measured
      Cd(II) uptake capacities from these experiments were of 1.2 mmol/g for Loy Yang
      and 0.7 mmol/g for Collie coals. This difference is ascribed to the larger
      concentrations of carboxyl groups in Loy Yang coal (2.78 mmol/g) compared to
      Collie coal (1.34 mmol/g). An adsorption isotherm for Loy Yang coal at p[H+] 6
      was collected up to a surface loading of 1.7 mmol/g of adsorbed Cd(II). These
      experiments also revealed a release of about 1.5-1.6 protons per adsorbed Cd(II).
      Zeta potentials of Loy Yang coal suspensions were not affected by Cd(II)
      adsorption, suggesting that the coal particles efficiently neutralize the charge
      of Cd(II). Collie coal, on the other hand, exhibited a zeta potential increase
      that may indicate a modification of the surface potentials of the coal particles.
      Cd(II) uptake data obtained from both batch experiments and proton balance data
      have been combined with p[H+] stat data for the same experimentally covered
      Cd(II)/coal ratios to model adsorption using the NICA-Donnan model. The modeling
      results suggest that both coals possess identical affinities and reaction
      stoichiometries. Loy Yang coal, however, possessed a narrower distribution of
      affinities.

PMID- 15450447
TI  - Study of influence on the surface energy heterogeneity of multiwalled carbon
      nanotubes after the adsorption of poly(acrylic acid).
AB  - The heterogeneity of the surface energy of multiwalled carbon nanotubes (MWNTs)
      before and after the adsorption of poly(acrylic acid) (PAA) at 77 K was
      investigated by a nitrogen probe adsorption technique in a wide range of
      pressures. The adsorption energy distributions (AEDs) were calculated from the
      low-pressure data of isotherms (i.e., the data of submonolayer adsorption) using
      the regularization method. Based on the AED, two types of dominant energetic
      surfaces are identified and assigned to the graphite-like carbon and disordered
      carbon or defects in the pure MWNTs, respectively. While the adsorption amount of
      PAA is raised, a significant decrease in the contribution of higher-energy
      surface in AEDs is observed for those PAA-adsorbed MWNTs. It is thus demonstrated
      that PAA prefers interacting with higher-energy surfaces to lower-energy surfaces
      in MWNTs. Nitrogen probe adsorption measurements including low-pressure data are
      shown to be a feasible and effective tool to characterize the heterogeneity of
      structure and surface properties of porous materials.

PMID- 15450448
TI  - Compaction of TiO2 suspension utilizing hydrophilic/hydrophobic transition of
      cationic thermosensitive polymers.
AB  - Compaction of TiO2 suspended particles utilizing the hydrophilic/hydrophobic
      transition of a cationic thermosensitive copolymer of N-isopropylacrylamide
      (NIPAM) and N-dimethylaminopropylacrylamide (DMAPAA) was examined. The surface of
      suspended TiO2 particles were sufficiently covered with the adsorbed polymer
      molecules at room temperature, and the suspension was subsequently heated above
      the transition temperature of the polymer. The thrusting motion of a plunger was
      used in order to provide an adequate mechanical force to compact the TiO2
      suspended particles. The transition temperature was dependent on the DMAPAA
      content in the copolymer and the pH of the suspension. The transition temperature
      increased with increasing DMAPAA content and decreased with increasing pH. While
      suspended TiO2 particles were not compacted with poly(NIPAM), hard compacted
      sludge was readily obtained for cationic copolymer even if the content of DMAPAA
      groups was as low as 0.23 mol%. Furthermore, residual polymer molecules in the
      supernatant were not detected even if the polymer dosage was increased. These
      findings were attributed to the hydrophobic interaction of thermosensitive
      copolymer molecules adsorbed on TiO2 particles.

PMID- 15450449
TI  - Studies on bovine serum albumin-sodium dodecyl sulfate complexes using pyrene
      fluorescence probe and 5-doxylstearic acid spin probe.
AB  - Interactions and characteristics of 0.1% bovine serum albumin (BSA)-sodium
      dodecyl sulfate (SDS) in 20 mM phosphate buffer solution were investigated by
      means of fluorescence spectroscopy and electron spin resonance (ESR)
      spectroscopy. In BSA-SDS system, the intensity ratio, Im3/Im1, of the third
      vibronic band of the pyrene monomer to the first vibronic band showed a small
      peak at about 0.1 mM SDS in the phosphate buffer below cmc. In accordance with
      this Im3/Im1 ratio, the intensity ratio, Ie/Im1, of fluorescence from the pyrene
      excimer to that from the monomer showed a pseudo-plateau (0.08-0.8 mM) and
      suggested the existence of micelle-like aggregates below the cmc. Temperature
      dependence of ln(Ie/Im1) in pyrene fluorescence in the SDS-BSA system was
      examined as a function of SDS concentration. The activation energy of pyrene
      diffusion for excimer formation in a micelle was estimated to be 19.2 kJ mol(-1)
      for the BSA-SDS system. ESR spectra of 5-doxylstearic acid (5-DSA) showed that
      the probe location is restricted at SDS concentrations above the cmc, and that
      the probe also is highly restricted in motion for BSA-bound SDS micelles.

PMID- 15450450
TI  - Fundamental studies on the intermediate layer of a bipolar membrane. Part II.
      Effect of bovine serum albumin (BSA) on water dissociation at the interface of a
      bipolar membrane.
AB  - This paper investigates the behavior of bovine serum albumin (BSA) during water
      dissociation on a bipolar membrane (BPM). BSA-modified BPM is prepared by
      immersing polyethylene anion exchange membrane in different concentration
      solutions of BSA, then casting the solution of sulfonated poly(phenylene oxide)
      (SPPO) in dimethyl formamide. The modification of BSA was evidenced by atomic
      force microscopy (AFM) and X-ray photoelectron spectroscopy (XPS). The junction
      thickness was evaluated by electrochemical impedance spectroscopy (EIS). The
      results showed that the typical I-V curves for bipolar membranes were heavily
      affected by the BSA modifications: the more the adsorbed amount of BSA, the
      larger the potential drop across a bipolar membrane. The new phenomena is
      underlined by the intrinsic properties of BSA molecules: steric effects give rise
      to an increase in the thickness of the depletion layer, amphoteric properties
      weaken the electric field of the junction, and hydrophobicity makes the junction
      less wet. All of these cause negative effects on water dissociation on a bipolar
      membrane.

PMID- 15450451
TI  - Apparent solubility distributions of hydroxyapatite and enamel apatite.
AB  - Samples of human dental enamel and hydroxyapatite were equilibrated at 5 mg/40 ml
      for 9 days at 37 degrees C with acetate buffers adjusted to a range of
      saturations with respect to hydroxyapatite. Sigmoidal apparent solubility
      distributions, in which the fraction dissolved was plotted against--log(ion
      activity product for hydroxyapatite) (pIHA), were constructed. About 10% of the
      hydroxyapatite and 14% of the enamel was very soluble, dissolving even at pIHA
      55. The apparent solubility distributions for both solids were invariant with pH
      (4.5, 5.0, 5.5), within experimental error, showing that solubility was
      controlled by a phase with the stoichiometry of hydroxyapatite, probably in the
      form of a surface layer or complex on the crystals, in agreement with other
      studies on carbonate-apatites and bone mineral. The pIHA at 50% dissolution was
      employed as an average value. The pIHA (50%) values for pooled data (58.76 for
      enamel and 60.17 for hydroxyapatite) were lower than the respective pIHA
      previously measured by conventional equilibration techniques. However, the
      average pIHA measured for enamel was higher than that obtained by the same
      technique in another study, possibly because of differences in specimen
      preparation and equilibration time. The possible implications of the findings for
      understanding the process of dental caries are discussed.

PMID- 15450452
TI  - Characteristics of interfacial water affected by proteins adsorbed on activated
      carbon.
AB  - The influence of proteins (bovine serum albumin, BSA, and mouse gamma-globulin,
      IgG) physically adsorbed or covalently attached via coupling with N-cyclohexyl-N'
      (2-morpholinoethyl) carbodiimide methyl-p-toluenesulfonate, CMC, to the surface
      of activated carbon SCN (spherical carbon with nitrogen) on the mobility of
      interfacial water molecules was studied by means of 1H NMR spectroscopy with
      freezing-out of bulk water at 180 < T < 273 K. Relaxation processes in the
      interfacial non-freezing water were investigated measuring transverse time t2 of
      proton relaxation dependence on the presence of proteins and CMC. The
      distribution function of activation free energy of relaxation (with a maximum at
      20-22 kJ/mol) was calculated for the protein-water-carbon systems using a
      regularization procedure and the relationships between t2 and the amounts of the
      interfacial water unfrozen at T < 250 K assuming the Arrhenius-type dependence
      for t2(-1) on temperature. The state of unfrozen water in pores of SCN shows that
      the low temperature relaxation processes occur in narrow pores with half-width X
      < 1.5 nm.

PMID- 15450453
TI  - Designing of nanostructured hollow TiO2 spheres obtained by ultrasonic spray
      pyrolysis.
AB  - Theoretical model describing the mechanism of droplet formation and structure of
      hollow TiO2 spheres prepared by the process of ultrasonic spray pyrolysis, using
      colloidal solution consisting of the 2.5-nm TiO2 nanoparticles as a precursor, is
      developed. The proposed model quantitatively defines each line in the size
      distribution spectrum. The mechanism of droplet formation and/or particle genesis
      is fully determined by harmonization between the physical fields inherent to the
      system as the consequence of its physical characteristics: external, e.g.,
      ultrasound, and internal. Agreement between theoretically obtained basic
      structural parameters (size distribution and geometry) and experimentally
      determined values was found.

PMID- 15450454
TI  - Particle size investigations of a multistep synthesis of PVA coated
      superparamagnetic nanoparticles.
AB  - Nanoscaled particles showing superparamagnetic behavior have been intensively
      studied in the past years for various applications. Nevertheless, the lack of
      well-defined particles remains an important problem. One of the major challenges
      is still the large-scale synthesis of particles with a narrow size distribution.
      The aim of this work is to synthesize and characterize ferrofluids throughout a
      multistep synthesis. The iron oxide nanoparticles are first obtained by classical
      coprecipitation in water, followed by a thermochemical treatment and
      centrifugation to obtain well-dispersed primary nanoparticles. Finally polyvinyl
      alcohol is grafted onto the particles to ensure colloidal stability of the
      ferrofluid at neutral pH. The different synthesis steps and intermediate and side
      products are described. A model is proposed for the stabilization mechanism.

PMID- 15450455
TI  - Cluster-cluster aggregation controlled by the number of intercluster connections:
      kinetics of aggregation and cluster mass frequency.
AB  - The aggregation of colloids in the presence of hydrodynamic forces was
      investigated, employing a numerical model that took into account the masses of
      the individual clusters and the number of intercluster connections established
      when two clusters stuck together. The number of possible connections was
      determined by analyzing all the possible nonoverlapping configurations of stuck
      clusters. This operation was done for a couple of clusters of various masses,
      taking into account the assembly of clusters of even and uneven masses. The
      formulation of the constraints established a certain hierarchy in the sticking on
      a basis compatible with the irregular fracture model of Horwatt and co-workers.
      As a result, the permanent sticking of large clusters required the formation of a
      large number of connections, whereas that of small clusters might be realized
      even with a small number of connections. Thus, the aggregation started with the
      features of the standard reaction-limited process and this cluster growth became
      progressively inhibited as a result of the prevailing effects of the connection
      constraints. The cluster-mass frequency showed the emergence at least of a second
      population whose bell-shaped mass distribution was superimposed on the
      monotonically decreasing distribution resulting from the reaction-limited
      aggregation process. The results of the numerical study were confronted with
      those previously obtained in the aggregation of hydrated polystyrene latex
      particles dispersed in 1 M sodium chloride solution. The two striking features-
      the aggregate growth kinetics and the mass distribution function--were common to
      the computer-generated clusters and the latex aggregates.

PMID- 15450456
TI  - Polymer-controlled synthesis of Fe3O4 single-crystal nanorods.
AB  - In this study, we describe a simple approach to preparing single-crystal Fe3O4
      nanorods in the presence of poly(vinylpyrrolidone) (PVP). The morphologies of the
      nanorods are characterized by transmission electron microscopy (TEM), which
      indicates that these nanorods are formed by nucleation and growth process in situ
      in aqueous solution. A superconducting quantum interference device (SQUID)
      magnetometer characteristic of the as-synthesized Fe3O4 nanorods shows
      superparamagnetic properties.

PMID- 15450457
TI  - Synthesis of micrometer to nanometer CaCO3 particles via mass restriction method
      in an emulsion liquid membrane process.
AB  - A mass restriction principle has been applied for the synthesis of precipitated
      calcium carbonate (PCC) with particle sizes from nanometer to micrometer via a
      simple emulsion liquid membrane (ELM) process. The internal liquid droplets in
      ELM were designed as individual microreactors in which the concentration and the
      total mass of the reaction chemicals were carefully mediated. Instrumental
      analysis, such as Fourier transform infrared (FTIR), wide X-ray diffraction
      (WXRD), scanning electron microscopy (SEM), and energy dispersive X-ray (EDX)
      analysis, confirmed a predominant calcite form of the final product via this
      process. The comparison of calculated particle sizes with that obtained from
      experimental measurements using dynamic light scattering (DLS), transmission
      electron microscopy (TEM) and SEM analysis suggested that approximately one PCC
      particle was formed in one water-in-oil (w/o) droplet.

PMID- 15450458
TI  - The hydrophilization of polystyrene substrates by 172-nm vacuum ultraviolet
      light.
AB  - This paper describes the photochemical surface modification of polystyrene (PS)
      substrates using vacuum ultraviolet (VUV) light 172 nm in wavelength. We have
      particularly focused on the effects of atmospheric pressure during VUV
      irradiation on the obtained surface's wettability and the stability of the
      wettability, in addition to its chemical structure, morphology, and
      photooxidation rate. Samples were photoirradiated with VUV light under pressures
      of 10, 10(3), or 10(5) Pa. Although, in each case, the originally hydrophobic PS
      surface became highly hydrophilic, the final water-contact angle and
      photooxidation rate depended on the atmospheric pressure. The samples treated at
      10 Pa were less wettable than those prepared at 10(3) and 10(5) Pa due to the
      shortage of oxygen molecules in the atmosphere. The minimum water-contact angles
      of the samples treated at 10, 10(3), and 10(5) Pa were about 8 degrees, 0
      degrees, and 0 degrees, respectively. With the samples prepared at 10 and 10(3)
      Pa, photooxidation reactions proceeded in the topmost region closest to the
      surface, while at 10(5) Pa photooxidation was found to be greatly enhanced in the
      deeper regions, as evidenced by angle-resolved X-ray photoelectron spectroscopy.
      Photoetching rates were determined through atomic force microscope observation of
      microstructured PS samples prepared by a simple mesh-contact method. As estimated
      from AFM images of the latticed microstructures obtained, the rates of samples
      prepared at 10(3) and 10(5) Pa were about 1.5 and 1.3 nm/min, respectively.
      However, no photoetched features were observable on the sample surface prepared
      at 10 Pa. Hydrophilic stability also varied greatly depending on atmospheric
      pressure. The hydrophilicity of samples treated at 10 and 10(3) Pa gradually
      decreased as they were exposed to air. On the other hand, the sample surface
      prepared at 10(5) Pa showed excellent hydrophilicity even after being left in air
      for 30 days.

PMID- 15450459
TI  - Inhibition of steel corrosion by calcium benzoate adsorption in nitrate
      solutions: theoretical and experimental approaches.
AB  - The inhibitive effects of calcium benzoate on steel corrosion were studied in
      sodium nitrate solutions at room temperature. Corrosion parameters of the
      steel/nitrate and steel/benzoate + nitrate interfaces were obtained from
      polarization curves. Adsorption parameters of benzoate on steel in sodium nitrate
      solutions were determined through changes in the degree of surface coverage by
      the inhibitor, as a function of concentration, time, and adsorption potential.
      The most likely adsorption configuration of benzoate on iron was envisaged with
      the help of semiempirical calculations such as extended Huckel calculations. A
      two-dimensional flat configuration was involving at least two metal atoms, one
      interacting with the phenolic group and the other with the carboxylate moiety.
      The effect of chloride on the corrosion inhibition of benzoate was analyzed by
      exposing the metal to different chloride solution concentrations, from which
      corrosion parameters were calculated and compared with those in nitrate
      solutions.

PMID- 15450460
TI  - A new equation for macroscopic description of capillary rise in porous media.
AB  - Capillary rise in porous media is frequently modeled using the Washburn equation.
      Recent accurate measurements of advancing fronts clearly illustrate its failure
      to describe the phenomenon in the long term. The observed underprediction of the
      position of the front is due to the neglect of dynamic saturation gradients
      implicit in the formulation of the Washburn equation. We consider an approximate
      solution of the governing macroscopic equation, which retains these gradients,
      and derive new analytical formulae for the position of the advancing front, its
      speed of propagation, and the cumulative uptake. The new solution properly
      describes the capillary rise in the long term, while the Washburn equation may be
      recovered as a special case.

PMID- 15450461
TI  - Preparation and application of dense poly(phenylene oxide) membranes in
      pervaporation.
AB  - Dense flat-sheet membranes were prepared from poly(2,6-dimethyl-1,4-phenylene
      oxide) (PPO) using the casting solvents chloroform and 1,1,2-trichloroethylene. X
      ray diffraction, tapping mode atomic force microscopy (TM-AFM), and contact angle
      studies were used to characterize the membranes. The surface energy and the
      solubility parameters of the PPO membranes were determined from the measured
      contact angles and compared with the predicted ones from the group contribution
      method. Swelling experiments and pervaporation separation of methanol from its
      mixture with ethylene glycol over the entire range of concentration, 0-100%, were
      conducted using these membranes. Flory-Huggins theory was used to predict the
      sorption selectivity. The results are discussed in terms of the solubility
      parameter approach and as function of the morphological characteristics of the
      membranes. It was found that PPO membranes prepared with chloroform exhibited
      better pervaporation performance than PPO membranes prepared with 1,1,2
      trichloroethylene.

PMID- 15450462
TI  - Macroporous Au materials prepared from colloidal crystals as templates.
AB  - In this paper, we reported the preparation of macroporous Au materials using
      organic colloidal crystals as templates and their catalytic activity for
      electroless copper deposition. The poly(styrene-methyl methacrylate-acrylic acid)
      (P(St-MMA-AA)) copolymer colloids were deposited in an orderly manner onto the
      silicon surface, together with the infiltration of the Au nanoparticles into the
      interspaces of the colloids. The formed hybrid colloidal crystal subsequently was
      sintered at approximately 550 degrees C to remove the organic components fully to
      obtain a macroporous Au framework with three-dimensional ordered porous
      structure. The pore diameter was around 310 nm and almost monodisperse. It was
      demonstrated that the macroporous Au materials exhibit catalytic activity and can
      induce electroless copper deposition.

PMID- 15450463
TI  - Adhesive contact based on the Lennard-Jones potential: a correction to the value
      of the equilibrium distance as used in the potential.
AB  - A Lennard-Jones type surface law is commonly used in adhesive contact modeling;
      however, one of its parameters, namely the equilibrium distance z0, is not well
      defined. In this paper, a self-consistent method is used to derive the Lennard
      Jones surface law from the interatomic Lennard-Jones potential. The parameters of
      the surface law are directly related to the material lattice parameter and
      surface energy, and the equilibrium distance z0 values are obtained for various
      materials. The effect of using the z0 proposed in the present work is
      demonstrated via the study of adhesive contact behavior for a single sphere and a
      flat surface, as well as the contact between planar rough surfaces. For pull-off
      force prediction of the contact between a single sphere and a flat surface, the
      error of using the z0 suggested in previous studies could be as large as 10% at
      intermediate ranges of a dimensionless adhesion parameter. For the contact
      between planar rough surfaces, the error of using the previously proposed z0 is
      larger for smoother cases, and the prediction of pull-off force could be
      different by as much as a factor of 5.

PMID- 15450464
TI  - Gas-vapor bubble nucleation--a unified approach.
AB  - In a solution which is saturated with gas near the superheat limit, one might
      expect a bubble formed from both dissolved gas and vapor molecules to appear. The
      integration of the surface-energy concepts, that are postulated on completely
      different physical bases for gas and vapor bubble formation is a major issue. In
      this paper, we reformulate gas and vapor bubble nucleation by a scaling
      transformation, which turns the surface energy for the bubble formation from both
      dissolved gases and vapor molecules to the translational energy of a molecule,
      (3/2)kBT. With this unified approach, one could estimate the dissolved gas effect
      on the superheat limit of the liquid. The driving force and the molecular volume
      are important quantities for determining the number of gas and vapor molecules
      composed of a critical cluster. This approach, of course, can predict pure gas
      bubble formation, as well as pure vapor bubble formation, as limiting cases.
      Also, this approach makes it possible to find that the possible occurrence of gas
      bubble nucleation by dissolved gases prevents measuring the theoretical superheat
      limit of water at atmospheric pressure, 300 degrees C.

PMID- 15450465
TI  - Spontaneous vesicle formation and vesicle-tubular microstructure transition in
      aqueous solution of a poly-tailed cationic and anionic surfactants mixture.
AB  - Spontaneous vesicle formation has been observed in aqueous mixtures of tri-(N
      dodecyldimethylhydroxypropylammonium chloride) phosphate (PTA) and bis-(2
      ethylhexyl) sulfosuccinate (Aerosol OT), which is supported by negative-staining
      TEM and dynamic light scattering. The range of vesicle formation in the PTA/AOT
      mixtures is wide and monodisperse vesicles are obtained. The vesicle diameter
      increases with the total surfactant concentration. Tubular microstructures,
      vesicle fusion, and vesicle-tubular microstructure transition have been also
      observed by negative-staining TEM. The vesicle formation mechanism is discussed
      from the viewpoint of molecular geometry, conformation, and the interaction
      between surfactant molecules.

PMID- 15450466
TI  - Study of mixtures of n-dodecyl-beta-D-maltoside with anionic, cationic, and
      nonionic surfactant in aqueous solutions using surface tension and fluorescence
      techniques.
AB  - Surfactants of practical interest are invariably mixtures of different types. In
      this study, mixtures of sugar-based n-dodecyl-beta-D-maltoside with cationic
      dodecyltrimethylammonium bromide, anionic sodium dodecylsulfate, and nonionic
      pentaethyleneglycol monododecyl ether in solution, with and without supporting
      electrolyte, have been studied using surface tension and fluorescence
      spectroscopic techniques. Interaction parameters and mole fraction of components
      in mixed micelles were calculated using regular solution theory. The magnitude of
      interactions between n-dodecyl-beta-D-maltoside and other surfactants followed
      the order anionic/nonionic > cationic/nonionic > nonionic/nonionic mixtures.
      Since all surfactants have the same hydrophobic groups, strengths of interactions
      are attributed to the structures of hydrophilic headgroups. Electrolyte reduced
      synergism between n-dodecyl-beta-D-maltoside and ionic surfactant due to charge
      neutralization. Industrial sugar-based surfactant, dodecyl polyglucoside, yielded
      results similar to that with dodecyl maltoside, implying that tested commercial
      alkyl polyglucosides are similar to the pure laboratory samples in synergistic
      interactions with other surfactants. Fluorescence study not only supported the
      cmc results using tensiometry, but showed that interfaces of all the above mixed
      micelle/solution interfaces are mildly hydrophobic. Based on these results, an
      attempt is made to discover the nature of interactions to be a combination of
      intermolecular potential energies and free energy due to packing of surfactant
      molecules in micelles.

PMID- 15450467
TI  - Aromatic nucleophilic substitution in nonionic alkylglucoside micelles.
AB  - The kinetics and mechanism of the aromatic nucleophilic substitution reaction of
      2,4-dinitrochlorobenzene (DNCB) with OH- in nonionic sugar-derived micelles were
      investigated and compared with those for reaction in polyoxyethylene glycol
      surfactants. Hydroxyl groups on the sugar headgroups of micellized n-nonyl beta-D
      glucopyranoside (C9G1), n-dodecyl beta-D-maltoside (C12G2), and n-dodecyl beta-D
      maltotrioside (C12G3) are partially deprotonated by OH- and the alkoxide ions
      react with DNCB, forming an arene ether. Observation of more than one isosbestic
      point indicates that more than one intermediate ether is formed, largely at C3 or
      C4 with micellar stereocontrol. Over time the ethers react with OH- giving 2,4
      dinitrophenoxide ion.

PMID- 15450468
TI  - Effect of the addition of water-soluble polymers on the interfacial properties of
      aerosol OT vesicles.
AB  - The properties of the interface of vesicles of pure sodium bis-(2-ethyl-hexyl)
      sulfosuccinate (AOT) and binary mixtures composed of AOT with poly(ethylene)
      glycol (PEG), poly(sodium 4-styrensulfonate) (PSS) and sodium chloride were
      investigated using absorption and steady-state fluorescence of nabumetone and
      electrophoretic mobility measurements. Results confirm those obtained in a
      previous work indicating that the addition of PEG, PSS, and NaCl stabilizes the
      AOT vesicles. The stabilization mechanism is the screening of the surface charge
      in the case of binary mixtures of AOT/PSS and AOT/NaCl and the polymer adsorption
      on the interface for vesicles of AOT/PEG.

PMID- 15450469
TI  - Sodium dodecyl sulfate-poly(amidoamine) interactions studied by AFM imaging,
      conductivity, and Krafft temperature measurements.
AB  - The conductivity, kappa, and Krafft temperature, TK, of sodium dodecyl sulfate
      (SDS) with poly(amidoamine) dendrimers (PAMAM) of 0.0, 0.5, and 1.0 generations
      (G) have been determined at different surfactant as well as PAMAM concentrations.
      The critical micelle concentration of SDS increases with the increase in the
      amount of each generation and the additive effect of 0.5G is maximum. TK of SDS
      shows a systematic decrease with maximum reduction in the presence of 0.5G.
      Atomic force microscopy (AFM) captures a layered pattern of 1.0G in the form of
      nanorods and no AFM images are detected for 1.0G in the presence of SDS. All
      results demonstrate that SDS has favorable interactions with ester-terminated
      0.5G PAMAM rather than amine-terminated 0.0G and 1.0G.

PMID- 15450470
TI  - Studies on dodecyl betainate in combination with its degradation products or with
      phosphatidyl choline-phase behavior and hemolytic activity.
AB  - Surface active betaine esters contain a hydrolysable bond and give naturally
      occurring products (fatty alcohol and the amino acid betaine) on degradation.
      They are therefore interesting candidates for use as cationic surfactants in
      pharmaceutical applications. In this work the phase behavior of two systems of
      relevance for the utilization of dodecyl betainate as a pharmaceutical excipient
      is studied, namely dodecyl betainate/dodecanol/betaine hydrochloride/D2O and
      dodecyl betainate/phosphatidyl choline (PC)/ethanol/D2O. The techniques used for
      phase characterisation were 2H NMR measured on the solvent, small angle X-ray
      spectroscopy and optical microscopy. Dilute dodecyl betainate/PC dispersions were
      characterized using laser diffraction. It is shown that introduction of
      relatively small amounts of the hydrolysis products of dodecyl betainate, i.e.,
      dodecanol and betaine (used in the form of betaine hydrochloride), has a strong
      effect on the phase behavior of the binary dodecyl betainate/D2O system. The
      degradation products change the average curvature of the surfactant film so that,
      instead of a hexagonal phase at concentrations above the micellar phase, a
      probably defective, lamellar phase seems to form. The dodecyl
      betainate/PC/ethanol/D2O system shows a large region of a highly swelling
      lamellar phase. Dispersions of dodecyl betainate/PC/ethanol in water can be
      prepared with low energy input; i.e., the preconcentrate can be regarded as a
      self-dispersing solution. Introduction of dodecyl betainate and its degradation
      products does not impair the ability of PC to form vesicles. Experiments for
      evaluating the toxicity of surface active betaine esters to erythrocytes were
      also performed. There are indications that the hemolytic activity of dodecyl
      betainate is lower than that of the stable surfactant tetradecyltrimethylammonium
      chloride, which has similar critical micelle concentration. A combination of
      dodecyl betainate and PC gives very low hemolytic activity.

PMID- 15450471
TI  - Microenvironmental differences and changes in bilayers of unilamellar vesicles
      probed by spectroscopic and kinetic parameters.
AB  - The UV/Vis absorption band maximum lambdamax of trans-4,4'
      nitrophenylaminoazobenzene, the thermal isomerization rate constant kiso of its
      cis-isomer, the fluorescence intensity ratio of monomer and excimer, and the
      fluorescence lifetime of the excimer, respectively, of 1,3-di(1-pyrenyl)propane
      were determined as probes for polarity, water content, and viscosity,
      respectively, in unilamellar vesicles of di-n-alkyl-dimethylammonium bromides and
      1,2-acyl-sn-glycero-3-phosphocholines. The dependence on vesicle size, the
      solvent (water or HEPES buffer/NaCl solution, each with H2O or D2O), and the
      temperature (20-60 degrees C) was studied. Apparent Arrhenius activation energies
      and kinetic solvent isotope effects (KSIE = kiso,H2O/kiso, D2O) were derived.
      Size and stability of the vesicles prepared by extrusion were controlled by
      dynamic light scattering. The probe properties clearly indicate the reversibly
      decreasing size of didodecyldimethylammonium bromide vesicles with increasing
      temperature but are insensitive against vesicles size variation in most other
      cases. In the temperature range of the main phase transition of the bilayers,
      changes of the microenvironment of the probes, and their changing position in the
      bilayer, respectively, are reflected by characteristic changes of their
      properties. Buffer/NaCl solution causes vanishing influence of the lipid chain
      but remaining difference between cationic and zwitterionic headgroups probed by
      means of kiso.

PMID- 15450472
TI  - Transient electroosmotic flow induced by DC or AC electric fields in a curved
      microtube.
AB  - This study investigates transient electroosmotic flow in a rectangular curved
      microtube in which the fluid is driven by the application of an external DC or AC
      electric field. The resultant flow-field evolutions within the microtube are
      simulated using the backwards-Euler time-stepping numerical method to clarify the
      relationship between the changes in the axial-flow velocity and the intensity of
      the applied electric field. When the electric field is initially applied or
      varies, the fluid within the double layer responds virtually immediately, and the
      axial velocity within the double layer tends to follow the varying intensity of
      the applied electric field. The greatest net charge density exists at the corners
      of the microtube as a result of the overlapping electrical double layers of the
      two walls. It results in local maximum or minimum axial velocities in the corners
      during increasing or decreasing applied electric field intensity in either the
      positive or negative direction. As the fluid within the double layer starts to
      move, the bulk fluid is gradually dragged into motion through the diffusion of
      momentum from the double layer. A finite time is required for the full momentum
      of the double layer to diffuse to the bulk fluid; hence, a certain phase shift
      between the applied electric field and the flow response is inevitable. The
      patterns of the axial velocity contours during the transient evolution are
      investigated in this study. It is found that these patterns are determined by the
      efficiency of momentum diffusion from the double layer to the central region of
      the microtube.

PMID- 15450473
TI  - Parathyroid hormone-related protein and lung biology.
AB  - Parathyroid hormone-related protein (PTHrP) is expressed in normal and malignant
      lung and has roles in development, homeostasis, and pathophysiology of injury and
      cancer. Its effects in developing lung include regulation of branching
      morphogenesis and type II cell maturation. In adult lung, PTHrP stimulates
      disaturated phosphatidylcholine secretion, inhibits type II cell growth, and
      sensitizes them to apoptosis. In lung cancer, PTHrP may play a role in carcinoma
      progression, or metastasis. The protein could be a useful marker for assessing
      lung maturity or type II cell function, predicting risk of injury, and detecting
      lung cancer. PTHrP-based therapies could also prove useful in lung injury and
      lung cancer.

PMID- 15450474
TI  - Phrenic, vagal and hypoglossal activities in rat: pre-inspiratory, inspiratory,
      expiratory components.
AB  - During eupnea in an in situ perfused preparation of the rat, inspiratory
      activities of the hypoglossal and vagal nerves commence before the phrenic; the
      vagus also discharges in expiration. The hypoglossal discharge has a prominent
      "pre-inspiratory" component. Power spectral analysis indicated that peak
      frequencies of oscillations in phrenic, hypoglossal and vagal inspiratory and
      expiratory activities were the same during eupnea. "Pre-inspiratory" hypoglossal
      activity had significantly lower peak frequencies. In gasping, "pre-inspiratory"
      hypoglossal activity ceased and all neural activities became purely inspiratory.
      High frequency oscillations of phrenic and vagal activities during gasping were
      shifted upward, compared to those in eupnea, whereas that of the hypoglossal was
      unaltered. In gasping, the temporal patterns of activities of the phrenic,
      hypoglossal and vagal nerves, and the level of coherence between these activities
      implies a restricted and shared set of pre-motor neurons. During eupnea, the
      activity patterns in the phrenic, hypoglossal and vagal nerves seem to originate
      from different sets of pre-motor neurons.

PMID- 15450475
TI  - Ventilatory effects of gap junction blockade in the NTS in awake rats.
AB  - We tested the hypothesis that focally perfusing carbenoxolone, which blocks gap
      junctions, into the nucleus tractus solitarius (NTS) would reduce the ventilatory
      response to CO(2). We measured minute ventilation (V(E)), tidal volume (V(T)) and
      respiratory frequency (F(R)) responses to increasing concentrations of inspired
      CO(2) (F(I)(CO(2) = 0-8%) in rats during wakefulness. Focal perfusion of
      acetazolamide (10 microM) into the NTS increased V(E) and V(T) during exposure to
      room air. Carbenoxolone (300 microM) decreased the V(E) and V(T) response to
      CO(2) when perfused within, but not adjacent to the NTS in animals less than 10
      weeks of age. F(R) was decreased at F(I)(CO(2) = 4% in these animals.
      Carbenoxolone did not decrease V(E), V(T) or F(R) in animals 10 weeks of age and
      older. Carbenoxolone did not decrease V(E), V(T) or F(R) when focally perfused
      outside the NTS at any age tested. The NTS is an important CO(2) chemosensory
      site at all ages, and gap junctions amplify the ventilatory response to CO(2) in
      animals less than 10 weeks of age.

PMID- 15450476
TI  - Increased hypoxic ventilatory response during 8 weeks at 3800 m altitude.
AB  - Acclimatization to chronic hypoxia (CH) increases ventilation (V(I)) and the
      isocapnic hypoxic ventilatory response (HVR) over 2-14 days but hypoxic
      desensitization blunts the HVR after years of CH. We tested for hypoxic
      desensitization during the first 2 months of CH by studying five normal subjects
      at sea level (SL) and for 8 weeks at 3800 m (CH, PI(O(2)) approximately 90 Torr).
      We measured the isocapnic HVR (Delta V(I)/Delta Sa(O(2)) and tested for hypoxic
      ventilatory decline (HVD) by stepping Sa(O(2)) to 80% after 14 min at 90%. The
      HVR increased significantly after 2 days and remained significantly elevated for
      8 weeks of CH. HVD was similar at SL and during 8 weeks of CH. Hence, hypoxic
      desensitization of the HVR does not occur after only 8 weeks of hypoxia and the
      increased HVR during this time does not involve changes in HVD.

PMID- 15450477
TI  - Developmental changes in transmission of respiratory rhythm in the rat.
AB  - We used cross-correlation to examine the short time-scale synchronisation of left
      and right phrenic nerve discharges in in-situ preparations of rats over a range
      of ages, to investigate the development of respiratory rhythm transmission to
      phrenic motoneurones. We found central peaks in the cross-correlograms,
      indicative of short time-scale synchronisation, at all ages (2-41 days), whose
      half-amplitude widths varied inversely with age (40-1.8 ms). In 10 preparations <
      or =5-days-old the central peaks were unaffected by a mid-sagittal section from
      C3 to C6. Carbenoxalone (CBX), a gap junction blocker, and its inactive analogue
      glycyrrhzic acid (GZA), eliminated central peaks in preparations younger than 12
      days but not in older preparations. We concluded that in rats older than
      approximately 12 days short time-scale synchronisation is produced by bilaterally
      projecting axons of medullary pre-motor neurones, whereas in younger rats it is
      due to pre-synaptic synchronisation of left and right medullary pre-motor
      neurones. While the latter mechanism may be gap junction connections, these
      experiments cannot unequivocally demonstrate it.

PMID- 15450478
TI  - Modulation of breathing by phasic pulmonary stretch receptor feedback in an
      amphibian, Bufo marinus.
AB  - This study examined the role of phasic pulmonary stretch receptor (PSR) feedback
      in ventilatory control, breath clustering and breath timing in decerebrate,
      paralysed and artificially-ventilated cane toads (Bufo marinus) under conditions
      designed to minimise tonic PSR feedback. Fictive breathing was recorded as
      trigeminal motor output to the buccal musculature. Artificial tidal ventilation,
      with hypercarbic gas mixtures, was either continuous or activated by the fictive
      breaths and was manipulated to provide differing amounts/patterns of phasic PSR
      feedback. The results demonstrate that increased amounts of phasic PSR feedback
      increase overall breathing frequency. Within multi-breath episodes there was an
      increase in the instantaneous breathing frequency during the later stages of the
      episode. The temporal relationship between a fictive breath and lung inflation
      influenced the duration of the pause between fictive breaths. The data indicate
      that phasic PSR feedback stimulates breathing by enhancing the occurrence of
      breathing episodes in this species but does not appear to modify the
      instantaneous breathing frequency during an episode.

PMID- 15450479
TI  - Persistence of diaphragmatic contraction influences the pulmonary inflammatory
      response to mechanical ventilation.
AB  - Because we already showed (Bregeon, F., Roch, A., Delpierre, S., Ghigo, E.,
      Autillo-Touati, A., Kajikawa, O., Martin, T., Pugin, J., Portugal, H., Auffray,
      J., Jammes, Y., 2002. Conventional mechanical ventilation of healthy lungs
      induced pro-inflammatory cytokine gene transcription, Respir. Physiol. Neurobiol.
      132, 191-203) that non-injurious mechanical ventilation (MV) elicited
      inflammatory signal in paralyzed rabbits having normal lungs, we examined the
      role of neuromuscular blockade in the pulmonary inflammatory response. In the
      bronchoalveolar lavage fluid (BALF), leukocyte count, MCP-1 and IL-8 cytokine
      concentrations (ELISA) and mRNAs (reverse transcription polymerase chain
      reaction, RT-PCR) were measured in paralyzed (P) or non-paralyzed (NP) rabbits
      ventilated for a 6-h period. Compared to the P group and despite the tidal volume
      was the same, we measured in the NP one a lower compliance of the respiratory
      system (Crs,stat), a longer inspiratory time (Ti), a negative inspiratory
      tracheal pressure (Ptr) wave preceding the pump-induced positive pressure wave,
      and a higher peak tracheal pressure. Moreover, in NP animals, gross autopsy
      showed negligible lung abnormalities, and marked reduction of leukocyte count and
      lung cytokines (P < 0.05). Thus, the absence of neuromuscular blockade decreased
      the pulmonary chemotactic response to MV suggesting that the total suppression of
      negative pressure waves elicited by the diaphragmatic (di) contractions could be
      involved in this lung response to positive pressure MV.

PMID- 15450480
TI  - Effects of prolonged exercise to exhaustion on left-ventricular function and
      pulmonary gas exchange.
AB  - The purpose of this study was to simultaneously examine left-ventricular (LV)
      function and pulmonary gas exchange during prolonged constant-rate cycling in an
      attempt to explain the exercise-induced impairment in gas exchange. Eleven
      competitive cyclists rode their racing bicycles on a computerized cycle trainer
      at 25 W below the lactate threshold until exhaustion (exercise time = 2.51 +/-
      0.86 h). LV systolic function was evaluated with two-dimensional echocardiography
      while arterial blood gases were used to assess pulmonary gas exchange. All
      variables were assessed concurrently before, during, and after exercise. LV
      function and cardiac output increased at the onset of exercise and were
      maintained until exhaustion. The alveolar-arterial P(O(2)) difference (A-a
      D(O(2))) increased within 15 min of the onset of exercise, was unchanged through
      to exhaustion, and returned to baseline 5 min post-exercise. Gas exchange was not
      related to cardiovascular function at the onset, or at end exercise. The results
      indicate that the widening A-aD(O(2)) during exercise is due to a readily
      reversible change in gas exchange function.

PMID- 15450481
TI  - Effect of work rate on the functional 'gain' of Phase II pulmonary O2 uptake
      response to exercise.
AB  - It has recently been reported that the 'gain' of Phase II increase in pulmonary
      oxygen uptake (i.e. the 'fundamental' increase in V(O(2)) per unit increase in
      work rate; G(p)) does not attain the anticipated value of approximately 10 ml
      min(-1)W(-1) following the onset of high-intensity exercise. In the present
      study, we hypothesised that G(p) would fall significantly below 10 ml min(-1)W(
      1) only when the work rate exceeded the so-called 'critical power' (CP). Seven
      healthy males completed several 'square-wave' transitions from 'unloaded' cycling
      to work rates requiring 60 and 90% of the gas exchange threshold (GET), 40 and
      80% of the difference between the GET and V(O(2)) peak (i.e. below and above the
      CP, respectively), and 100, 110 and 120% of V(O(2)) peak. Pulmonary V(O(2)) was
      measured breath-by-breath and V(O(2)) kinetics were determined using non-linear
      regression techniques. The asymptotic G(p) was significantly lower at work rates
      above (7.2-8.6 ml min(-1)W(-1)) compared to work rates below (9.3-9.7 ml min(
      1)W(-1)) the CP (P < 0.05). We conclude that the gain of Phase II increase in
      V(O(2)) becomes significantly reduced when the work rate exceeds the CP.

PMID- 15450482
TI  - Modulation of experimentally-induced cough by stimulation of nasal mucosa in cats
      and guinea pigs.
AB  - Stimulation of afferent nerves in upper airways may contribute to the
      pathogenesis of chronic cough in chronic disorders of nose and/or sinuses. We
      tested the hypothesis that stimulation of the nasal afferent nerves enhances
      experimentally-induced cough. Intranasal administration of capsaicin (50 microM,
      25 microl) did not evoke cough in anaesthetized cats, but enhanced cough induced
      by mechanical stimulation of the tracheobronchial mucosa (number of coughs,
      median [IQR]) (6.5 [5.5-8.5] versus 10 [7-14]; P = 0.028, n = 13). In contrast,
      intranasal histamine (16 mM, 25 microl) had no effect. Intranasal capsaicin (50
      microM, 15 microl) did not evoke cough, but enhanced cough evoked by mechanical
      stimulation of the tracheobronchial mucosa (1 [1-3] versus 3 [2-4]; P = 0.0037, n
      = 15) in anaesthetized guinea pigs and cough induced by inhalation of citric acid
      (0.3M, 2 min) in awake guinea pigs (3 [2-5] versus 5 [3-7], P ? 0.0026, n = 23).
      We conclude that stimulation of nasal afferent nerves with capsaicin enhances
      experimentally-induced cough. Our results suggest that afferent inputs from the
      nose interact with the cough reflex pathways in a manner that enhances cough.

PMID- 15450483
TI  - Effect of hypothermia on respiratory rhythm generation in hamster brainstem
      spinal cord preparations.
AB  - This study examined the effect of hypothermia on respiratory neural output from
      brainstem-spinal cord preparations of a cold tolerant rodent, the Syrian hamster.
      Brainstem-spinal cords from neonatal hamsters (0-6 days) were placed in a
      recording dish and respiratory-like neural activity was recorded from roots of
      the first cervical nerve. The preparations were cooled and warmed in a continuous
      or stepwise fashion. Inputs from the pons completely inhibited neural activity
      under steady state conditions. With the pons removed, fictive breathing was
      robust. Cooling caused respiratory arrest, followed by spontaneous resumption of
      activity on re-warming. Preparations from older hamsters (4-6 days old) were more
      cold tolerant than younger preparations (0-3 days old). Motor discharge was
      episodic during continuous cooling, and seizure-like discharge was observed
      during continuous warming. These phenomena were not observed with stepwise
      temperature changes suggesting that transient temperature effects on membrane
      properties may be involved. These preparations were not as cold tolerant as
      hamster pups in vivo but they retained the ability to autoresuscitate at all ages
      studied.

PMID- 15450484
TI  - Contribution of lymphatic drainage through stomata to albumin removal from
      pleural space.
AB  - The contribution of lymphatic drainage through the stomata of parietal
      mesothelium to the overall removal of labeled albumin from the pleural space was
      found 89% in sheep with very large hydrothoraces (10 ml/kg), a condition
      involving a approximately 20 times increase in lymphatic drainage [Broaddus et
      al., J. Appl. Physiol. 64 (1988) 384]. We determined this contribution in
      anesthetized rabbits with small (0.12 ml/kg) and large (2.4 ml/kg) hydrothoraces
      of Ringer-albumin with labeled albumin and labeled dextran-2000 kDa. This dextran
      was used as marker of liquid removal through the stomata because it should
      essentially leave the pleural space through the stomata only, owing to its size.
      The removal of labeled albumin by lymphatic drainage through the stomata was 39%
      of the overall removal in the small hydrothoraces, and 64% in the large ones.
      Hence, lymphatic drainage through the stomata does not contribute most of protein
      and liquid removal from the pleural space under physiological conditions, as it
      has been maintained. It markedly increases with the increase in pleural liquid
      volume.

PMID- 15450485
TI  - The elucidation of fascinating new enzyme-catalysed reactions continues.

PMID- 15450486
TI  - Glycine reductase mechanism.
AB  - The ability of some anaerobic bacteria to conserve energy via a soluble substrate
      level phosphorylation system by reducing glycine to acetyl-phosphate has been an
      intriguing mechanism for about half a century. The genes implicated in this
      system have been sequenced and form an operon structure with those of the
      thioredoxin system. The deduced proteins exhibit high degrees of similarity with
      glycine reductase from other bacteria. Faster progress in understanding the exact
      mechanisms is hampered, for example, by some unique reactions involving
      selenoethers and redox active selenocysteines, which do not allow an easy
      heterologous formation in Escherichia coli. Further major obstacles are the
      processing of a substrate-specific pro-protein to a new carbonyl/pyruvoyl group
      in one of the two peptides formed that stabilize the substrate-binding
      selenoprotein, which contains an additional rather unstable carbonyl group.

PMID- 15450487
TI  - ATP-driven electron transfer in enzymatic radical reactions.
AB  - A novel method to generate organic radicals in enzymatic reactions is described,
      which is similar to electron transfer in nitrogenase. Component A of 2
      hydroxyglutaryl-CoA dehydratase contains a [4Fe-4S] cluster located at the
      interface between its two identical subunits. The cluster is reduced by one
      electron derived from ferredoxin or flavodoxin. Hydrolysis of two ATP bound to
      component A, one to each subunit, enhances the reductive power of the electron
      and transfers it to component D, the actual dehydratase, where a low potential
      [4Fe-4S](2+) cluster is probably reduced. Further transfer to the substrate (R)-2
      hydroxyglutaryl-CoA probably generates a substrate-derived ketyl radical anion,
      which expels the adjacent hydroxyl group. The resulting enoxy radical is
      deprotonated to a product-related ketyl radical anion. Finally the electron is
      removed by the next incoming substrate leading to the product glutaconyl-CoA and
      starting a new turnover. A similar, but stoichiometric rather than catalytic
      electron transfer has been established for the related benzoyl-CoA reductase.

PMID- 15450488
TI  - Structure and function of radical SAM enzymes.
AB  - 'Radical SAM' enzymes juxtapose a [4Fe-4S] cluster and S-adenosyl-l-methionine
      (SAM) to generate catalytic 5'-deoxyadenosyl radicals. The crystal structures of
      oxygen-independent coproporphyrinogen III oxidase HemN and biotin synthase reveal
      the positioning of both cofactors with respect to each other and relative to the
      surrounding protein environment. Each is found in an unprecedented coordination
      environment including the direct ligation of the [4Fe-4S] cluster by the amino
      nitrogen and one carboxylate oxygen of the methionine moiety of SAM, as observed
      for other members of the Radical SAM family by ENDOR. The availability of two
      protein structures supported by biochemical and biophysical data underscores
      common features, anticipating the structural elements of other family members.
      Remaining differences emphasize the plasticity of the protein scaffold in
      functionally accommodating 600 family members.

PMID- 15450489
TI  - Radical mechanisms in adenosylcobalamin-dependent enzymes.
AB  - Adenolsylcobalamin-dependent enzymes catalyze free radical mediated reactions of
      their substrates. Stereochemical methods have been used to establish the nature
      of the primary radical initiation step in ribonucleoside triphosphate reductase.
      Kinetic isotope effects have been used to establish a kinetic coupling between
      cobalt-carbon bond cleavage and hydrogen atom abstraction from the substrate.
      Isotope effects have also been used to identify rate-limiting steps with wild
      type and mutant forms of the enzymes and in model reactions to assess tunneling
      contributions to hydrogen atom transfer steps. Computational methods have been
      employed to explore the pathways for functional group migration in the radical
      pathways. Analogs of substrates and of adenosylcobalamin have been used to
      explore the fidelity of the enzyme active sites and the radical pathways.

PMID- 15450490
TI  - Function of genetically encoded pyrrolysine in corrinoid-dependent methylamine
      methyltransferases.
AB  - Methanogenesis from trimethylamine, dimethylamine or monomethylamine is initiated
      by a series of corrinoid-dependent methyltransferases. The non-homologous genes
      encoding the full-length methyltransferases each possess an in-frame UAG (amber)
      codon that does not terminate translation. The amber codon is decoded by a
      dedicated tRNA, and corresponds to the novel amino acid pyrrolysine in one of the
      methyltransferases, indicating pyrrolysine to be the 22nd genetically encoded
      amino acid. Pyrrolysine has the structure of lysine with the (epsilon)N in amide
      linkage with a pyrroline ring. The reactivity of the electrophilic imine bond is
      the basis for the proposed function of pyrrolysine in activating and optimally
      orienting methylamine for methyl transfer to the cobalt ion of a cognate
      corrinoid protein. This reaction is essential for methane formation from
      methylamines, and may underlie the retention of pyrrolysine in the genetic code
      of methanogens.

PMID- 15450491
TI  - Mechanism of action of S-ribosylhomocysteinase (LuxS).
AB  - S-Ribosylhomocysteinase (LuxS) cleaves the thioether bond in S
      ribosylhomocysteine to produce homocysteine and 4,5-dihydroxy-2,3-pentanedione.
      This reaction serves the dual purposes of detoxification of S
      adenosylhomocysteine and production of type 2 quorum sensing molecule. Recent
      research has shown that LuxS uses Fe(2+) to catalyze an internal redox reaction,
      shifting the ribose carbonyl group from its C1 to C3 position. Subsequent beta
      elimination completes this highly unusual reaction. LuxS and other enzymes on the
      same pathway may provide a novel class of antibacterial drug targets.

PMID- 15450492
TI  - Post-translational modifications during lantibiotic biosynthesis.
AB  - Recent reports have provided the first insights into the mechanisms of the
      extensive post-translational modifications involved in the biosynthesis of the
      lantibiotics, a class of peptide antimicrobial agents. These modifications
      involve dehydration of several serine and threonine residues followed by
      intramolecular conjugate additions of cysteines, resulting in extensively cross
      linked polycyclic structures. Both in vivo and in vitro studies indicate low
      substrate specificity of the modification machinery, which has been explored for
      re-engineering of the structures of a number of members. In addition to these
      developments in understanding their biosynthesis, studies on the mode of action
      of several lantibiotics have shown a unique mechanism of binding to lipid II, an
      intermediate in cell wall biosynthesis.

PMID- 15450493
TI  - Enzymatic reactions involving novel mechanisms of carbanion stabilization.
AB  - The reactions catalyzed by orotidine monophosphate decarboxylase, oxalate
      decarboxylase, organomercurial lyase and phosphopantothenoylcysteine
      decarboxylase involve putative high-energy carbanion intermediates that cannot be
      stabilized by delocalization. Mechanistic and structural studies on each of these
      enzymes are described that suggest different strategies for carbanion
      stabilization. Both orotidine monophosphate decarboxylase and organomercurial
      lyase are likely to avoid carbanion formation by protonating the fragmenting
      bond, oxalate decarboxylase stabilizes an acyl carbanion using an adjacent
      radical and phosphopantothenoylcysteine decarboxylase stabilizes its carbanion by
      delocalization into a transient thioaldehyde.

PMID- 15450495
TI  - Native protein mass spectrometry: from intact oligomers to functional
      machineries.
AB  - The development of electrospray ionization coupled to mass spectrometry has
      enabled the analysis of very large intact protein complexes, even when they are
      held together by weak non-covalent interactions. Together with equally
      spectacular advances in mass spectrometric instrumentation, a new field has
      emerged, termed native protein mass spectrometry, which focuses on the structural
      and functional analysis of the dynamics and interactions occurring in protein
      complexes. In the past two years, several important progressive steps in
      technologies have been reported that have led to exciting applications ranging
      from the detailed study of equilibria between different quaternary structures as
      influenced by environmental changes or binding of substrates or cofactors, to the
      analysis of intact nano-machineries, such as whole virus particles, proteasomes
      and ribosomes.

PMID- 15450496
TI  - Monolithic columns for high-efficiency HPLC separations.
AB  - Monolithic columns have been studied as materials, having advantages inherent to
      their network-type one-piece structures. These columns demonstrably provide
      generally higher performance than conventional particle-packed columns in
      pressure-driven liquid chromatography, based on their higher external porosity.
      The use of such columns has just started in many areas.

PMID- 15450497
TI  - Raman spectroscopy in chemical bioanalysis.
AB  - Advances in instrumentation are making Raman spectroscopy the tool of choice for
      an increasing number of (bio)chemical applications. Raman is an interesting
      option for several reasons, including the sensitivity to small structural
      changes, non-invasive sampling capability, minimal sample preparation, and high
      spatial resolution in the case of Raman micro-spectroscopy. Herein we discuss the
      most recent technical approaches employed, from the well-known surface enhanced
      resonance Raman spectroscopy to non-linear Raman techniques such as coherent anti
      stokes Raman spectroscopy (CARS) and related techniques. Relevant applications of
      Raman spectroscopy in the fields of clinical pathology, in vivo and ex vivo
      imaging, classification and detection of microorganisms and chemical analysis in
      the past three years are also included.

PMID- 15450498
TI  - Optochemical nanosensor PEBBLEs: photonic explorers for bioanalysis with
      biologically localized embedding.
AB  - Nanosized photonic explorers for bioanalysis with biologically localized
      embedding (PEBBLEs) have been created for the intracellular monitoring of small
      analytes (e.g. H(+), Ca(2+), Mg(2+), Zn(2+), O(2), K(+), Na(+), Cl(-), OH and
      glucose). The probes are based on the inclusion of fluorescent analyte-sensitive
      indicator dyes and analyte-insensitive reference dyes in a polymer
      (polyacrylamide, polydecylmethacrylate) or sol-gel (silica, ormosil)
      nanoparticle. The probes are ratiometric, reversible and protected from
      interaction with the cellular environment, a quality which is of benefit to the
      integrity of both the cell and the sensor functionalities. Herein we describe two
      types of PEBBLE sensors, direct measurement sensors and ion correlation sensors,
      as well as the use of these PEBBLEs in intracellular sensing.

PMID- 15450499
TI  - Molecular beacons.
AB  - This opinion covers the field of molecular beacons (MBs), in which nucleic acids
      are molecularly engineered to have unique functions for the investigation of
      biomolecules. Molecular beacons have been used in a variety of formats, and this
      review discusses four: first, in vitro RNA and DNA monitoring; second, biosensors
      and biochips based on MBs; third, real-time monitoring of genes and gene
      expression in living systems; and finally, the next generation of molecular
      beacons that will be highly useful for studies with proteins, molecular beacon
      aptamers. These unique applications have shown that MBs holds great potential in
      genomics and proteomics where real-time molecular recognition with high
      sensitivity and excellent specificity is critical.

PMID- 15450500
TI  - Peptide arrays: towards routine implementation.
AB  - Peptide arrays have attracted wide interest as tools for discovering biochemical
      interactions. Because many protein binding and enzyme activities are directed
      towards peptides, the preparation of arrays having hundreds to thousands of
      immobilized peptides offers an unprecedented opportunity for identifying
      interactions of proteins. This short opinion reviews recent progress in the
      preparation of peptide arrays and their use in the characterization of
      biomolecular interactions and the discovery of new reagents for biological
      researches. This body of work establishes the feasibility of this technology and
      suggests that it will find much wider use in research groups.

PMID- 15450501
TI  - The role of analytical sciences in medical systems biology.
AB  - Medical systems biology has generated widespread interest because of its bold
      conception and exciting potential, but the field is still in its infancy.
      Although there has been tremendous progress achieved recently in generating,
      integrating and analysing data in the medical and pharmaceutical field, many
      challenges remain, especially with respect to the crucial core technologies
      required for analytical characterization. This review briefly summarizes these
      aspects for metabolomics, proteomics, data handling and multivariate
      biostatistics.

PMID- 15450502
TI  - Perceptual enhancement of contrast by attention.
AB  - Allocating spatial attention to a visual stimulus or increasing stimulus contrast
      both enhance neuronal responses. In a recent study Carrasco et al. demonstrated
      that attention itself changes perceived contrast. Using an elegant experimental
      manipulation, they showed that the contrast of an attended stimulus was perceived
      to be higher than when the same stimulus was unattended. This provides evidence
      that the enhancement of stimulus salience observed in electrophysiological
      studies creates an enhanced perceptual representation of attended stimuli.

PMID- 15450503
TI  - Algebra and the adolescent brain.
AB  - New fMRI evidence suggests that adolescents could be at an advantage for learning
      algebra compared with adults. Qin and colleagues present findings indicating that
      after several days of practice adolescents rely on prefrontal regions to support
      the retrieval of algebraic rules to solve equations, as do adults. Unlike adults,
      however, after practice adolescents decrease their reliance on parietal regions,
      which assist in the transformation of the equations, suggesting an enhanced
      ability for learning algebra. These findings are discussed with regard to
      adolescent brain maturation.

PMID- 15450504
TI  - What causes scale errors in children?
AB  - A recent article by DeLoache et al. has documented an intriguing phenomenon in
      the development of action planning in young children. When children act on toy
      replicas of larger objects they make scale errors that are consistent with the
      full-sized object. Although the actions selected are inappropriate, their
      execution accurately takes into account the true size of the target. This
      phenomenon permits tests of the predictions of the perception-action and planning
      control models of vision for action.

PMID- 15450505
TI  - A common neural system signaling the need for behavioral changes.

PMID- 15450507
TI  - The mental number line: exact and approximate.

PMID- 15450509
TI  - Universal Grammar, statistics or both?
AB  - Recent demonstrations of statistical learning in infants have reinvigorated the
      innateness versus learning debate in language acquisition. This article addresses
      these issues from both computational and developmental perspectives. First, I
      argue that statistical learning using transitional probabilities cannot reliably
      segment words when scaled to a realistic setting (e.g. child-directed English).
      To be successful, it must be constrained by knowledge of phonological structure.
      Then, turning to the bona fide theory of innateness--the Principles and
      Parameters framework--I argue that a full explanation of children's grammar
      development must abandon the domain-specific learning model of triggering, in
      favor of probabilistic learning mechanisms that might be domain-general but
      nevertheless operate in the domain-specific space of syntactic parameters.

PMID- 15450510
TI  - The reverse hierarchy theory of visual perceptual learning.
AB  - Perceptual learning can be defined as practice-induced improvement in the ability
      to perform specific perceptual tasks. We previously proposed the Reverse
      Hierarchy Theory as a unifying concept that links behavioral findings of visual
      learning with physiological and anatomical data. Essentially, it asserts that
      learning is a top-down guided process, which begins at high-level areas of the
      visual system, and when these do not suffice, progresses backwards to the input
      levels, which have a better signal-to-noise ratio. This simple concept has proved
      powerful in explaining a broad range of findings, including seemingly
      contradicting data. We now extend this concept to describe the dynamics of skill
      acquisition and interpret recent behavioral and electrophysiological findings.

PMID- 15450511
TI  - How the brain separates sounds.
AB  - In everyday life we often listen to one sound, such as someone's voice, in a
      background of competing sounds. To do this, we must assign simultaneously
      occurring frequency components to the correct source, and organize sounds
      appropriately over time. The physical cues that we exploit to do so are well
      established; more recent research has focussed on the underlying neural bases,
      where most progress has been made in the study of a form of sequential
      organization known as "auditory streaming". Listeners' sensitivity to streaming
      cues can be captured in the responses of neurons in the primary auditory cortex,
      and in EEG wave components with a short latency (< 200ms). However, streaming can
      be strongly affected by attention, suggesting that this early processing either
      receives input from non-auditory areas, or feeds into processes that do.

PMID- 15450512
TI  - How language acquisition builds on cognitive development.
AB  - When children acquire a first language, they build on what they know--conceptual
      information that discriminates and helps create categories for the objects,
      relations and events they experience. This provides the starting point for
      language from the age of 12 months on. So children first set up conceptual
      representations, then add linguistic representations for talking about
      experience. Do they then discard earlier conceptual representations in favour of
      linguistic ones, or do they retain them? Recent research on the coping strategies
      that young children (and adults) rely on when they are unable to draw on language
      suggest that they retain both types of representations for use as needed.

PMID- 15450513
TI  - [Iodin 125 seed migration after prostate brachytherapy: a study of 170 patients].
AB  - PURPOSE: To study the number of migrating seeds, the anatomical site of migration
      and possible predictive parameters of migration, after prostate cancer
      brachytherapy using a loose-seed (I125) implantation technique. PATIENTS AND
      METHODS: The charts of the 170 patients consecutively treated by the Institut
      Curie/Hospital Cochin/Hospital Necker Group between September 1, 2001 and August
      31, 2002, were analysed. All seeds having migrated to the lungs and seen on the
      chest X-ray systematically performed at 2 months, have been recorded, as well as
      the seeds lost by the urines (after sieving) or in the sperm (condom). RESULTS:
      Among 12,179 implanted seeds, 44 were found to have migrated (0.36%). Most of the
      migrating seeds (32/44; 73%), were found in the lungs. Overall, one or several
      seed migrations were observed in 35 patients (21% of the total number of patients
      in this series). In the majority of cases (77%), only one seed migrated. A
      significant relationship (P = 0.04) was found between the number of migrating
      seeds and the number of implanted ones (or with the prostate volume, but those
      two parameters were closely linked in our series). More specifically, a
      significant relationship (P = 0.02) could be demonstrated between the number of
      seeds implanted at the periphery of the prostate and the number of seeds
      migrating to the lungs. CONCLUSION: The percentage of migrating seeds observed in
      this series is low, actually one of the lowest found in the literature when using
      the loose-seed technique. There was no clinical consequences and the loss of
      usually-only one seed is very unlikely to alter the quality of the dose
      distribution. However, the predominance of pulmonary migrations in our series led
      us to slightly modify our implantation technique. We now try to avoid too
      "peripheral" seed implantations, due to the risk of migration towards the
      periprostatic veins, and subsequently to the lungs.

PMID- 15450514
TI  - [Surgical and radiotherapeutic approaches according to postoperative margins
      analysis in breast cancer: survey realized in 20 French cancer centers].
AB  - Margin status is regarded as a major prognostic factor for local recurrence after
      breast conservative treatment. Margin definition in the literature is not always
      clear and precise. The impact on the therapeutic management may be quite
      different. This paper presents the radiotherapeutic attitude according to a
      survey realized in the twenty French cancer centers. The surgical practice in
      terms of margins status is appraised. The radiotherapist attitude in terms of
      boost's modulation is specified.

PMID- 15450515
TI  - Clinical and anatomical guidelines in pelvic cancer contouring for radiotherapy
      treatment planning.
AB  - BACKGROUND AND PURPOSE: Many observations on potential inadequate coverage of
      tumour volume at risk in advanced cervical cancer (CC) when conventional
      radiation fields are used, have further substantiated by investigators using MRI,
      CT or lymphangiographic imaging. This work tries to obtain three dimensional
      margins by observing enlarged nodes in CT scans in order to improve pelvic nodal
      chains clinical target volumes (CTVs) drawing, and by looking for corroborative
      evidence in the literature for a better delineation of tumour CTV. METHOD: Eleven
      consecutive patients (seven males, four females, mean age 62 years, range 43-78)
      with CT diagnosis of nodal involvement caused by pathologically proved carcinoma
      of the cervix (n = 2), carcinoma of the rectum (n = 2), carcinoma of the prostate
      (n = 2), non-Hodgkin lymphoma (n = 2), Hodgkin lymphoma (n = 1), carcinoma of the
      penis (n = 1) and carcinoma of the corpus uteri (n = 1) were retrospectively
      reviewed. Sixty CT scans with 67 enlarged pelvic nodes were reviewed in order to
      record the more proximal structures (muscle, bone, vessels, cutis or subcutis and
      other organs) to each enlarged node or group of nodes according to the four
      surfaces (anterior, lateral, posterior and medial) in a clockwise direction.
      RESULTS: A summary of the observations of each nodal chain and the number of
      occurrences of every marginal structure on axial CT slices is presented. Finally,
      simple guidelines are proposed. CONCLUSIONS: Tumour CTV should be based on
      individual tumour anatomy-mainly for lateral beams as it results from sagittal T2
      weighted MRI images. Boundaries of pelvic nodes CTVs can be derived from
      observations of enlarged lymph nodes in CT scans.

PMID- 15450516
TI  - Influence of MRI abnormality in skull base bone on prognosis of nasopharyngeal
      carcinoma.
AB  - PURPOSE: To evaluate the influence of skull base bone (SBB) abnormality showed by
      MRI on prognosis of nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: From
      March 1993 to December 1998, 122 NPC patients received prime radiotherapy
      treatment. All of them were proved pathologically and checked by magnetic
      resonance imaging (MRI). Every patient received radiation through conjoint facio
      cervical field and conventional dose-fractionation schedules. The total dose to
      the primary tumor was 60-75 Gy (median, 70 Gy). The Kaplan-Meier method, the Log
      rank test and the Cox regression model were used to evaluate the significance of
      prognostic factors on NPC patient survival. RESULTS: The overall median survival
      period was 50 (6-92) months, and the 1, 3 and 5 year-survival rates were,
      respectively, 99.2%, 87.9%, and 73.3%. The 1, 3, and 5 year-survival rates of
      abnormality and normality of the SBB on MRI were 98.9%, 87.2%, 71.9%, and 100.0%,
      89.8%, 77.0%, respectively (P = 0.4233). Gender, age, head pain, SBB abnormality,
      cranial nerve palsy, cervical lymphadenopathy and primary tumor extent were
      analyzed with the Cox regression model and SBB abnormality on MRI did not prove
      to have statistical significance (P = 0.6934). According to the analysis of
      regrouping, patients with SBB abnormalities > or =2 sites have a worse prognosis
      (P = 0.0427). Then, the above seven factors are analyzed by Cox regression model
      and the result had statistical significance (P = 0.0385). CONCLUSION: The SBB
      abnormality on MRI is of no obvious influence on prognosis of NPC. However, when
      SBB abnormality sites were > or =2, there is obvious statistical significance on
      the prognosis.

PMID- 15450517
TI  - [Constraints to organs at risk for treatment of head and neck cancers by
      intensity modulated radiation therapy].
AB  - Constraint definitions in intensity modulated radiation therapy is a key point
      factor during the treatment planning process. In literature some data are
      available about dose constraints and volumes according to the tissue
      architectures. Following ICRU recommendations, organs at risk organized in a
      parallel structure could receive an acceptably small proportion of high dose
      component. Mean dose and dose volume histogram is a most convenient tool for
      incorporating such constraints. Organs described as a serial structure are
      supposed to receive less than the given maximum dose, directly linked to the
      occurrence of complications. Dmax is the best way to describe such events. These
      constraints are new tools in radiation therapy, available for optimizing the dose
      distribution in target volume, sparing the organs at risk to protect the organ
      function or at least decreasing the late functional damages like xerostomia. It
      is necessary to define with accuracy gross target volumes and clinical target
      volume with available radio-anatomical guidelines before introducing current
      constraints on each volume in the inverse dosimetry. The management of these
      constraints remains under the responsibility of the clinicians. A permanent
      compromise has to be chosen between homogeneity of the dose distribution in the
      target volume and the probability of preserving functions of organs at risk.

PMID- 15450518
TI  - [Brachytherapy boost for breast cancer: what do we know? Where do we go?].
AB  - Since many years, Brachytherapy (BT) appears to play an important role in the
      treatment of many solid tumors. For breast cancer, BT is usually used as boost
      after postoperative external beam radiation therapy. In certain circumstances, BT
      can be used as sole radiation technique focalized on the tumor bed or more
      rarely, as second conservative treatment in case of local recurrence for woman
      refusing salvage mastectomy. Boost BT is most often applied via an interstitial
      technique while the dose rate can vary from low to high dose rate through pulse
      dose rate. All of those boost techniques were published and some of them compared
      the results obtained with BT and external beam electron therapy. The analysis of
      the published phase II and III trials was not able to show significant
      differences between the two boost techniques in term of local control as well as
      late skin side effects. However, we noted that the patients who received BT boost
      presented a higher risk of local recurrence compare to those treated with
      electron therapy, due to age, margin status or presence of extensive intraductal
      component. Only a phase III trial randomizing BT boost vs electron therapy boost
      could show a possible improvement of local control rate in the BT arm; however,
      this trial should enroll patients with a real high risk of local recurrence in
      order to take benefit from the dosimetric advantages of BT.

PMID- 15450519
TI  - [Comparison of intensity-modulated postoperative radiotherapy with conventional
      postoperative conformal radiotherapy for retroperitoneal sarcoma].
AB  - External postoperative radiation therapy for retroperitoneal sarcoma is an
      example of treatment using large fields for complex shaped volumes of
      irradiation. Prescribed dose is limited by tolerance of adjacent organs at risk
      (OAR). From a recent case treated by conventional conformal radiotherapy (3D
      CRT), we evaluate the benefit of five theoretical IMRT plans. Criteria used are
      calculated from DVH related to delineated PTV and OAR. IMRT should permit to
      enhance the prescribed dose without increasing dose in the OAR (especially
      residual kidney, spinal cord and small bowel). This theoretical study show the
      feasibility of a dose escalation from a treatment dose of 45 Gy delivered by 3D
      CRT up to a planning dose of 54 Gy calculated by IMRT with: for the PTV: an
      improvement of the dose homogeneity about 5% (range 2-6%) and moreover the
      coverage factor (CF) about 13% (range 9-16%); for the OAR: an improvement of the
      protection factor (PF) about 20% (range 11-24%); and thus an improved conformity
      index (CI = CF x PF) about 25% (range 15-32%).

PMID- 15450520
TI  - Presence of human papillomavirus-18 and Epstein-Barr virus in a squamous cell
      carcinoma of the tongue in a 20-year-old patient. Case report and review of the
      current literature.
AB  - We report on a squamous cell carcinoma of the tongue in a 20-year-old woman with
      co-infection of the tumor with human papilloma virus type 18 and Epstein-Barr
      virus. To our knowledge, this is the first case of co-infection in carcinoma of
      the tongue to be reported. We review the present data and theories concerning
      viral oncogenesis of oral carcinomas.

PMID- 15450521
TI  - [Squamous cell carcinoma complicating an hereditary epidermolysis bullosa].
AB  - The dystrophic form of hereditary epidermolysis bullosa is associated with an
      increased frequency of squamous cell carcinoma. We report a new case. An 18-year
      old patient, carrying a Hallopeau Siemens hereditary epidermolysis bullosa,
      presented a subcutaneous nodular lesion, for 1 year that ulcerated and budded
      with inguinal lymphadenopathy. The histological study led to the conclusion of a
      well differentiated squamous cell carcinoma. The patient was treated surgically.
      Tumor and metastatic lymph nodes were excised. A radiotherapy was decided but the
      postoperative course was fatal due to an infection and to a deterioration of her
      general condition. Squamous cell carcinoma frequently occurs on the cicatricial
      lesion of hereditary epidermolysis bullosa and usually affects males with
      recessive hereditary epidermolysis bullosa. Metastases are frequent, precocious
      and multiple. The treatment may be surgical. The particularities of our
      observation are the young age of patient and the localization.

PMID- 15450522
TI  - [Basal cell carcinoma of the scalp after radiation therapy for tinea capitis: 33
      patients].
AB  - Occurrence of basal cell carcinoma (BCC) following radiotherapy for tinea capitis
      is well known. The aim of this study was to specify the clinical and histological
      features of these BCC seen in 33 patients (1995-2000). Twenty seven men and six
      women were diagnosed with BCC. The age of onset varied between 32 an 62 years.
      Radiotherapy was received between 5 and 17 years of age. The interval between
      irradiation and the onset of carcinoma varied between 21 and 51 years. Total
      number of lesions was 55. Forty percent of BCC occurred on the occipital area,
      the number varied from 1 to 5 and the size from 2 to 45 mm. Clinically, the
      nodular type was found in 51% of cases. Pigment was present in 64% of cases.
      Histological study showed a nodular aspect in 76% and pigmentation in 63% of
      cases. Nodular and pigmented type were the predominant BCC occurring after
      radiotherapy for tinea capitis in our series. In the literature, BCC are the most
      frequent carcinomas occurring after radiotherapy (70-100%). Pigmentation was not
      described in other series. The nodular histological form was the most frequent.

PMID- 15450523
TI  - [Patient education in oncology: Proceedings of the XX Congress of the French
      Society of Psycho-Oncology. 5-6 December 2003, Lyon, France].

PMID- 15450524
TI  - [Cervical cancer associated with HIV in young Congolese women. Preliminary
      study].

PMID- 15450525
TI  - Influence of the quality of tibial plateau alignment on the reproducibility of
      computer joint space measurement from Lyon schuss radiographic views of the knee
      in patients with knee osteoarthritis.
AB  - RATIONALE: The quality of medial tibial plateau (MT-Plateau) alignment is one of
      the key elements for accuracy and sensitivity to change of knee radiography in
      knee osteoarthritis (OA). AIM: To evaluate the influence of the quality of the MT
      Plateau alignment on the reproducibility of joint space width (JSW) measurement
      in knee radiographs. METHODS: One hundred and twenty-seven knee radiographs (99
      OA), performed using a standardized radiographic procedure (Lyon schuss (LS)
      view). Evaluation of the quality of MT-Plateau alignment. Computerized
      measurement of the JSW, twice, 1-month apart, using a semi-automated and an
      automated method of measurement. Assessment of the reproducibility of repeated
      measurements: calculation of intra-observer coefficient of correlation, smallest
      detectable difference (SDD) and coefficient of variation (CV). RESULTS: MT
      Plateau alignment was satisfactory in 99 radiographs (77.9%). Reproducibility was
      excellent in both satisfactory and non-satisfactory radiographs, irrespective of
      the method of measurement used. The automated measurement was more reproducible
      than the semi-automated one (CV 1.15% and 3.23%). SDD and CV were better in
      satisfactory than in non-satisfactory MT-Plateau aligned radiographs. CONCLUSION:
      These results confirm that computer measurement of the medial tibio-femoral JSW,
      from LS digitized radiographs, is highly reproducible, irrespective of the
      quality of the radiograph. However, the quality of the MT-Plateau alignment
      influences the reproducibility of JSW measurement. The automated measurement was
      more reproducible than the semi-automated one.

PMID- 15450526
TI  - Expression and localization of connective tissue growth factor (CTGF/Hcs24/CCN2)
      in osteoarthritic cartilage.
AB  - OBJECTIVE: The investigation of the expression and localization of connective
      tissue growth factor/hypertrophic chondrocyte-specific gene product 24/CCN family
      member 2 (CTGF/Hcs24/CCN2) in normal and osteoarthritic (OA) cartilage, and
      quantification of CTGF/Hcs24-positive cells. METHODS: Cartilage samples of
      patients (n=20) with late stage OA were obtained at total joint replacement
      surgery. Morphologically normal cartilage was harvested for comparison purposes
      from the femoral heads of 6 other patients with femoral neck fracture. Paraffin
      embedded sections were stained by Safranin O. The severity of the OA lesions was
      divided into four stages (normal, early, moderate, and severe). The localization
      of protein and mRNA for CTGF/Hcs24 was investigated by immunohistochemistry and
      in situ hybridization, respectively. The population of CTGF/Hcs24-positive
      chondrocytes in OA cartilage and chondro-osteophyte was quantified by counting
      the number of the cells under light microscopy. RESULTS: Signals for CTGF/Hcs24
      were detected in a small percentage of chondrocytes throughout the layers of
      normal cartilage. In early stage OA cartilage, the CTGF/Hcs24-positive
      chondrocytes were localized mainly in the superficial layer. In moderate to
      severe OA cartilage, intense staining for CTGF/Hcs24 was observed in
      proliferating chondrocytes forming cell clusters next to the cartilage surface.
      In chondro-osteophyte, strong signals were found in the chondrocytes of the
      proliferative and hypertrophic zones. CONCLUSION: CTGF/Hcs24 expression was
      detected in both normal and OA chondrocytes of human samples. The results of the
      current study suggested that expression of CTGF/Hcs24 was concomitant with
      development of OA lesions and chondrocyte differentiation in chondro-osteophyte.

PMID- 15450527
TI  - Dose-response relationship for exercise on severity of experimental
      osteoarthritis in rats: a pilot study.
AB  - OBJECTIVE: To investigate the influence of a calibrated exercise on the
      progression of structural lesions in an experimental model of osteoarthritis (OA)
      in the rat, and to explore the effect of exercise on the level of chondrocyte
      caspase-dependent apoptosis and of Hsp70. METHODS: The OA model was induced by
      anterior cruciate ligament transection (ACLT). Rats were placed in 4 experimental
      groups: operated (ACLT) free moving rats, and 3 exercise groups (slight, moderate
      and intense) subjected to running training. Rats were killed 14 and 28 days after
      surgery. RESULTS: On D14 histological assessment demonstrated a beneficial
      influence of a slight and a moderate exercise vs control ACLT group. Hsp70
      increased significantly in the moderate group vs controls. On D28, histological
      lesions strongly decreased in the slight and moderate exercise groups vs ACLT
      group, while an intense effort abolished this beneficial trend. Interestingly,
      the concomitant course of apoptotic events (caspase 3-positive cells) and the co
      expression of Hsp70 in the various groups varied, when significant, in an inverse
      manner. In the intense group this overexpression was not noted, as a "burn out"
      appeared, thus leading to a loss of this protective effect. CONCLUSION: This
      study shows that a calibrated slight or moderate exercise exerts a beneficial
      influence on the severity of chondral lesions in ACLT rats. Conversely, a strong
      effort abolishes this chondroprotective effect. This effect could be related to a
      reduced level of chondrocyte apoptosis through anti-apoptotic capacities of
      stress-induced Hsp70 overexpression.

PMID- 15450528
TI  - Cryoprotectant permeation through human articular cartilage.
AB  - OBJECTIVE: The cryopreservation of intact articular cartilage is constrained by
      minimal chondrocyte survival. It was the aim of the present study to gain an
      insight into the permeation kinetics of cryoprotectants through cartilage. This
      knowledge is essential for achieving adequate tissue permeation prior to cooling.
      DESIGN: The diffusion coefficients and penetration rates through human articular
      cartilage of dimethyl sulfoxide (Me(2)SO) and glycerol at different temperatures
      (4 degrees C, 17 degrees C, 27 degrees C and 37 degrees C) and at two
      concentrations [10% (v/v) and absolute state] were measured using diffusion
      nuclear magnetic imaging. Deuterated water (D(2)O) was used as a control
      substance. RESULTS: Glycerol penetrated faster than Me(2)SO at all temperatures
      and at rates that were comparable to those for D(2)O. The penetration rate of
      each agent increased with increasing temperature. The diffusion coefficients for
      glycerol and Me(2)SO increased with increasing temperature and decreased at the
      higher concentration, but the differences between each agent were not
      significant. CONCLUSIONS: The classical cryopreservation protocols expose
      cartilage samples to Me(2)SO at a too low temperature and/or for an insufficient
      time period for optimal cell survival. When considering the penetration rate,
      glycerol appears to be a more efficient cryoprotective agent than Me(2)SO. The
      present study demonstrates the power of nuclear magnetic resonance technology to
      elucidate key physiological factors in cryobiology.

PMID- 15450529
TI  - Effects of physical stimulation with electromagnetic field and insulin growth
      factor-I treatment on proteoglycan synthesis of bovine articular cartilage.
AB  - OBJECTIVE: To investigate the single and combined effects of electromagnetic
      field (EMF) exposure and the insulin growth factor-I (IGF-I) on proteoglycan (PG)
      synthesis of bovine articular cartilage explants and chondrocytes cultured in
      monolayers. DESIGN: Bovine articular cartilage explants and chondrocyte
      monolayers were exposed to EMF (75Hz; 1.5mT) for 24h in the absence and in the
      presence of both 10% fetal bovine serum (FBS) and IGF-I (1-100ng/ml). PG
      synthesis was determined by Na(2)-(35)SO(4) incorporation. PG release into
      culture medium was determined by the dimethylmethylene blue (DMMB) assay.
      RESULTS: In cartilage explants, EMF significantly increased (35)S-sulfate
      incorporation both in the absence and in the presence of 10% FBS. Similarly, IGF
      I increased (35)S-sulfate incorporation in a dose-dependent manner both in 0% and
      10% FBS. At all doses of IGF-I, the combined effects of the two stimuli resulted
      additive. No effect was observed on medium PG release. Also in chondrocyte
      monolayers, IGF-I stimulated (35)S-sulfate incorporation in a dose-dependent
      manner, both in 0% and 10% FBS, however, this was not modified by EMF exposure.
      CONCLUSIONS: The results of this study show that EMF can act in concert with IGF
      I in stimulating PG synthesis in bovine articular cartilage explants. As this
      effect is not maintained in chondrocyte monolayers, the native cell-matrix
      interactions in the tissue may be fundamental in driving the EMF effects. These
      data suggest that in vivo the combination of both EMF and IGF may exert a more
      chondroprotective effect than either treatment alone on articular cartilage.

PMID- 15450530
TI  - Differential regulation of chondrocyte metabolism by oncostatin M and interleukin
      6.
AB  - OBJECTIVE: To determine the effects of interleukin (IL)-6 and oncostatin M (OSM)
      added separately or in combination with IL-1beta on human osteoarthritic (OA)
      chondrocytes in alginate beads. DESIGN: Human chondrocytes were isolated from OA
      cartilage and cultured in alginate beads for 12 days, in the absence or in the
      presence of increasing amounts of IL-6 (20-500ng/ml) with its soluble receptor or
      OSM (0.1-10ng/ml) and with or without IL-1beta (1.7ng/ml). Aggrecan (AGG),
      transforming growth factor-beta1 (TGF-beta1), stromelysin-1 [matrix
      metalloprotease (MMP)-3], tissue inhibitor of metalloproteinases-1 (TIMP-1),
      macrophage inflammatory protein-1 beta (MIP-1beta), IL-6 and IL-8 productions
      were assayed by specific enzyme amplified sensitivity immunoassays. Prostaglandin
      (PG)E(2) was measured by a specific radioimmunoassay and nitrite (NO(2)(-)) by a
      spectrophotometric method based upon the Griess reaction. RESULTS: OSM, but not
      IL-6, decreased basal AGG and TGF-beta1 synthesis. Although IL-6 stimulated basal
      TIMP-1 production, it did not significantly modify MMP-3/TIMP-1 ratio. In
      contrast, 10ng/ml OSM highly increased TIMP-1 production, and decreased by half
      the ratio MMP-3/TIMP-1. IL-1beta highly stimulated *NO, IL-8, IL-6, MIP-1beta and
      PGE(2) synthesis but decreased AGG and TGF-beta1 production. Neither IL-6 nor OSM
      modulated IL-1beta-inhibitory effect on AGG production. IL-6, but not OSM,
      reversed IL-1beta-induced TGF-beta1 inhibition. At 1-10ng/ml, OSM significantly
      decreased IL-1beta-stimulated IL-8, MIP-1beta, PGE(2) and *NO production but
      amplified IL-1beta stimulating effect on IL-6 production. IL-6 had no effect on
      these parameters. CONCLUSIONS: OSM and IL-6, two glycoprotein 130 binding
      cytokines, show different activity profiles on OA chondrocytes, indicating that
      these cytokines could play different roles in the OA disease process.

PMID- 15450531
TI  - Fate of transplanted bone-marrow-derived mesenchymal cells during osteochondral
      repair using transgenic rats to simulate autologous transplantation.
AB  - OBJECTIVE: The fate of transplanted cells used in tissue engineering strategies
      should be followed. With this aim in view, the survival of transplanted bone
      marrow-derived mesenchymal cells within osteochondral defects was determined
      using transgenic rats to simulate autologous transplantation. DESIGN: An
      autologous transplantation model was simulated using transgenic rats - whose
      transgenes produce no foreign proteins - as donors, and wild-type rats as
      recipients. Dense masses of mesenchymal cells were prepared from the transgenic
      rats using the hanging-drop culture technique. These cell masses were then
      transplanted into osteochondral defects created within the medial femoral condyle
      of wild-type rats, wherein they are affixed with fibrin glue. The course of
      repair was assessed histologically. The survival of the transplanted cells was
      ascertained by in situ hybridization of the transgenes. RESULTS: Twenty-four
      weeks after transplantation, the defects were repaired with hyaline-like
      cartilage, which was thicker than normal, and with subchondral bone. Using the in
      situ hybridization technique, cells derived from the transplanted ones were
      detected within both the cartilaginous and the subchondral bone layers.
      CONCLUSION: Using this simulated autologous transplantation model, the survival
      of transplanted mesenchymal cells was monitored in vivo. The findings indicate
      that the transplanted mesenchymal cells contributed to the repair of the
      osteochondral defects.

PMID- 15450532
TI  - The potential and limitations of cartilage-specific (V+C)(-) fibronectin and
      cartilage oligomeric matrix protein as osteoarthritis biomarkers in canine
      synovial fluid.
AB  - OBJECTIVE: To determine if levels of the cartilage-specific (V+C)(-) fibronectin
      isoform in the synovial fluid is associated with cartilage change during
      osteoarthritis. DESIGN: Synovial fluid was collected from 26 healthy dogs
      presenting to the Orthopedic Surgery Clinic with unilateral cranial cruciate
      rupture, 22 control dogs, and 13 dogs from a colony maintained for the study of
      canine hip dysplasia. Total fibronectin, (V+C)(-) fibronectin, and cartilage
      oligomeric matrix protein (COMP) were quantitated by ELISA assays. Statistical
      analysis used Wilcoxon's signed-rank and rank-sum tests and Spearman's rank
      correlation. RESULTS: The concentration of total fibronectin was increased in
      affected (P<0.0001) and contralateral (P=0.0005) knees of the clinic population
      (compared to unaffected knees in colony controls). Both (V+C)(-) fibronectin and
      COMP concentrations were elevated in the contralateral knees in clinical patients
      relative to unaffected knees in the colony controls (P=0.03 and P=0.04,
      respectively), and relative to the affected knees (P=0.003); however, corrections
      for joint effusions suggest elevated totals in the affected knees. (V+C)(-)
      fibronectin and COMP concentrations were correlated (r(sp)=0.74; P<0.0001) in 30
      unaffected knees of patients and colony controls. Total fibronectin was
      correlated negatively with months since the initial injury (r(sp)=-0.44; P=0.03)
      in the affected joints. The intraoperative lesion severity score did not
      correlate with total fibronectin or (V+C)(-) fibronectin (P>or=0.35).
      CONCLUSIONS: Concentration of total fibronectin in synovial fluid might be a
      useful biomarker for cross-sectional studies in osteoarthritis, but only (V+C)(-)
      fibronectin provides information specifically about cartilage damage. Elevated
      concentrations of (V+C)(-) fibronectin and COMP seen in the contralateral knees
      of patients with cranial cruciate rupture might indicate cartilage changes early
      in the disease process (pre-clinical). However, the wide range of values obtained
      limits the diagnostic value for any one individual. Joint effusions obscure the
      total amount of biomarkers in affected synovial joints.

PMID- 15450533
TI  - Site- and exercise-related variation in structure and function of cartilage from
      equine distal metacarpal condyle.
AB  - OBJECTIVE: Determine (1) the site-associated response of articular cartilage of
      the equine distal metacarpal condyle to training at a young age as assessed by
      changes in indentation stiffness and alterations in cartilage structure and
      composition, and (2) relationships between indentation stiffness and indices of
      cartilage structure and composition. METHOD: Experimental animals (n=6) were
      trained on a track (increasing exercise to 1km/day by 5 months); controls (n=6)
      were pasture-reared. Animals were euthanized at 18 months and four osteochondral
      samples were harvested per metacarpal condyle from dorsal-medial, dorsal-lateral,
      palmar-medial, and palmar-lateral aspects. Cartilage was analyzed for India ink
      staining (quantified as reflectance score (RS)), short-term indentation stiffness
      (sphere-ended, 0.4mm diameter), thickness, and biochemical composition. RESULTS:
      Cartilage structural, biochemical and biomechanical properties varied markedly
      with site in the joint. Sites just medial and just lateral to the sagittal ridge
      showed signs of early degeneration, with relatively low RS, indentation
      stiffness, and collagen content, and relatively high water content. Effects of
      exercise and side (left vs right) were not detected for any measure. Overall,
      indentation stiffness correlated positively with RS and collagen content, and
      inversely with thickness and water content. CONCLUSION: Gentle exercise-imposed
      mechanical stimulation did not markedly affect articular cartilage function or
      structure. However, the marked site-associated variation suggests that
      biomechanical environment can initiate degenerative changes in immature cartilage
      during joint growth and maturation.

PMID- 15450534
TI  - One day exposure to FGF-2 was sufficient for the regenerative repair of full
      thickness defects of articular cartilage in rabbits.
AB  - OBJECTIVES: Administration of fibroblast growth factor (FGF)-2 for 2 weeks
      induces a successful cartilaginous repair response in 5-mm full-thickness
      articular cartilage defects in rabbits. The purpose of this study was to
      investigate the effects of a short time exposure to FGF-2 on the repair of the
      defects. METHODS: Five-mm-diameter cylindrical defects, which do not repair
      spontaneously, were created in the femoral trochlea of the rabbit knees. The
      defects were administered sterile saline or FGF-2 (150pg/h) via an osmotic pump
      for the initial 1 day, 3 days, or 2 weeks, and we assessed the FGF-2 action on
      the proliferation and migration of mesenchymal cells in the reparative tissue.
      Using a total of 126 rabbits, we performed three sets of experiments. We also
      studied the effect of FGF-2 on migration of marrow-derived mesenchymal cells in
      vitro. RESULTS: FGF-2 treatment for 1 day or 3 days induced the sequential
      chondrogenic repair responses that led to successful cartilaginous resurfacing of
      defects within 8 weeks as well as the 2-week treatment did. We confirmed by a
      radioisotope study that FGF-2 injected was rapidly eliminated from the defects (a
      residual ratio of 50% within 30min). The effect of FGF-2 on cultured marrow
      derived cells suggested that FGF-2 facilitated the mobilization and migration of
      replicating mesenchymal cells from bone marrow. CONCLUSIONS: Only 1 day exposure
      to FGF-2 is sufficient for induction of the chondrogenic repair response in 5-mm
      diameter full-thickness defects of articular cartilage in rabbits. FGF-2
      stimulated the recruitment of mesenchymal cells into the defects, which was a
      limiting step for the induction of cartilage.

PMID- 15450535
TI  - Analysis of cartilage biomarkers in erosive and non-erosive osteoarthritis of the
      hands.

PMID- 15450536
TI  - Cutting cartilage--surgical perspective.

PMID- 15450538
TI  - Emergency contraception for adolescents: the time to act is now.

PMID- 15450540
TI  - Recent research findings on aggressive and violent behavior in youth:
      implications for clinical assessment and intervention.
AB  - Assessing children and adolescents for potential violent behavior requires an
      organized approach that draws on clinical knowledge, a thorough diagnostic
      interview, and familiarity with relevant risk and protective factors. This
      article reviews empirical evidence on risk factors, the impact of peers,
      developmental pathways, physiological markers, subtyping of aggression, and
      differences in patterns of risk behaviors between sexes. We explore these
      determinants of violence in children and adolescents with attention to the
      underlying motivations and etiology of violence to delineate the complexity,
      unanswered questions, and clinical relevance of the current research.
      Interventions, including cognitive behavioral therapy, psychopharmacological
      treatment, and psychosocial treatment, are reviewed with acute recognition of the
      need to use multiple modalities with, and to expand research to define optimal
      treatment for, potentially violent children and adolescents. The information
      considered for this review focuses on violence as defined as physical aggression
      toward other individuals. Other studies are included with wider definitions of
      violence because of their relevance to assessing the potential for violent
      behavior.

PMID- 15450541
TI  - Unhealthy weight management behavior among adolescent girls with type 1 diabetes
      mellitus: the role of familial eating patterns and weight-related concerns.
AB  - PURPOSE: To explore familial eating patterns and weight-related concerns among
      families of adolescent girls with type 1 diabetes mellitus (DM) and to examine
      associations with disordered eating behaviors among the girls. METHODS:
      Interviews were conducted with 30 adolescent girls (ages 13-20 years), who had DM
      for at least 1 year, and separately with their parents. Eighty-four percent of
      the girls were Caucasian, 13% were African-American, and 3% were Hispanic. The
      sample included 15 girls who reported (on a questionnaire) engaging in disordered
      eating behaviors (DE) and a matched comparison group of girls who reported no
      disordered eating (Non-DE). The semi-structured interview questions focused on
      adolescent and parent perceptions of the impact of DM on family roles,
      relationships, and routines, as well as who does what in managing the DM. A
      content analysis of the interviews identified themes regarding family meal
      patterns and weight-related issues. RESULTS: Although variation was found, more
      than one-half (57%) of the families were classified as having a high level of
      meal structure (e.g., frequent family meals). Families with DE girls were more
      likely to be classified as having a low level of meal structure (e.g., infrequent
      family meals) than families with Non-DE girls. Weight concerns were common;
      nearly half (48%) of all families were classified as having a high level of
      weight-related concerns (e.g., at least one member having a high desire to lose
      weight). The prevalence of families with a parent engaging in behaviors to lose
      weight and/or making negative comments about eating or weight was higher in
      families of DE girls than Non-DE girls. The combination of low family meal
      structure and high familial weight concerns was much more prevalent in families
      with DE girls (58%) than in families of non-DE girls (7%). CONCLUSIONS:
      Interactions around food and weight appear common in many families of adolescent
      girls with DM. Whereas frequent family meals may help to defend against
      disordered eating in youth with DM, family weight concerns and behaviors appear
      to be risk factors for disordered eating.

PMID- 15450542
TI  - An evaluation of an Internet-delivered eating disorder prevention program for
      adolescents and their parents.
AB  - PURPOSE: To evaluate the effectiveness of Student Bodies, an Internet-delivered
      eating disorder prevention program for adolescents, and a supplemental program
      for their parents. METHODS: One hundred fifty-two 10th grade females completing a
      health course at a private sectarian school, and 69 of their parents were
      assigned to either the Internet-delivered intervention group or to a comparison
      group (students) or wait-list control group (parents). Student participants
      completed subscales of the Eating Disorder Inventory, Eating Disorder Examination
      Questionnaire, and a content knowledge test. Parents completed the Parental
      Attitudes and Criticism Scale. RESULTS: The main effects of the intervention were
      assessed pre- to post- and post- to follow-up using ANCOVA, with the baseline
      assessment of the independent variable as the covariate. Students using the
      program reported significantly reduced eating restraint and had significantly
      greater increases in knowledge than did students in the comparison group.
      However, there were no significant differences at follow-up. Parents
      significantly decreased their overall critical attitudes toward weight and shape.
      CONCLUSION: The program demonstrates the feasibility of providing an integrated
      program for students and their parents with short-term positive changes in
      parental attitudes toward weight and shape.

PMID- 15450543
TI  - Perception of disease severity in adolescents diagnosed with neurofibromatosis
      type 1.
AB  - PURPOSE: To examine the relationship between adolescents' families' perception of
      the severity of neurofibromatosis (NF1) and the clinical severity of NF1, a
      genetic condition with variable manifestations. METHODS: The Perception of
      Severity of Chronic Illness (PSCI) questionnaire was administered to 56 parents
      of 47 adolescents with NF1. Each participant was asked one open-ended question
      regarding the challenges of living with NF1. Scores assessing the clinical
      severity of NF1 were assigned by health care providers in the NF Clinic.
      Correlation coefficients and paired t-test were used to evaluate the relationship
      between the clinical severity and the families' perceptions. Qualitative data
      were reviewed and grouped into themes. RESULTS: Parental perceptions were
      correlated with the degree of medical (r = 0.3116, p <.05), cognitive (r =
      0.4911, p <.0001), and behavioral (r = 0.3341, p <.05) impairment of the
      adolescent. Adolescent perception was correlated with the degree of cognitive
      impairment (r = 0.5429, p <.0001). Parental and adolescent perceptions were
      correlated (r = 0.6724, p <.0001); however, adolescents viewed the condition's
      impact as being less than their parents (p <.001). The qualitative data provide
      additional insight into the concerns of these families. CONCLUSIONS: Families
      dealing with more medical, cognitive, and behavioral complications of NF1
      perceive the impact of the condition on daily life as being greater than those
      families with fewer complications. The quantitative and qualitative results of
      this study have several implications for the clinical care of adolescents with
      NF1 and their families.

PMID- 15450544
TI  - Adolescents in mid-sized and rural communities: foregone care, perceived
      barriers, and risk factors.
AB  - PURPOSE: To investigate the perceived health care needs, foregone care, barriers
      to care, and associated risk factors in a non-urban population of adolescents.
      METHODS: Tenth-grade students attending school and 15-17-year-old youth not
      attending school in a Midwestern county were surveyed or interviewed. Eighty-six
      percent provided usable data (n = 1948, 134 of whom were not in school). Nine
      focus groups (71 participants; 28 were not in school) were conducted in follow
      up. Quantitative analysis included descriptive statistics, factor analysis, and
      logistic regression. Qualitative analysis of taped focus groups identified themes
      and interpreted findings. RESULTS: Although 91% had seen a physician in the past
      2 years, 44% reported foregoing needed care in the last year. Barriers for
      specific health needs were: cost of care and lack of insurance coverage for
      injuries and illnesses; lack of knowledge, distrust, and stigma for depression;
      embarrassment and transportation for birth control and sexually transmitted
      infections (STIs); and not knowing where or how to access care for drug and
      alcohol use. Youth most likely to have foregone care included those involved with
      dangerous activities under peer pressure (1.8, CI: 1.44-2.13), sexual intercourse
      (1.4, CI: 1.25-1.67), marijuana use (1.4, CI: 1.17-1.67), anticipating parenthood
      before age 20 years (1.2, CI: 1.04-1.33), male gender (2.5, CI: 1.89-2.86) and
      perceiving good health (1.7, CI: 1.45-1.85). CONCLUSIONS: Nearly half of this non
      urban population (both in and out of school) reported foregoing needed care in
      the last year. The barriers to care include lack of information, lack of access,
      poor insurance coverage, parenting issues, and concern about confidentiality.

PMID- 15450545
TI  - Disparities in routine physical examinations among in-school adolescents of
      differing Latino origins.
AB  - PURPOSE: To estimate the prevalence of routine physical examination among in
      school adolescents of differing national Latino origins and to assess
      associations with gender, age, immigrant generational status, language spoken at
      home, parental education, poverty level, family structure, and insurance status.
      METHODS: Cross-sectional analysis of Wave I of the National Longitudinal Study of
      Adolescent Health conducted during 1995. Our sample was limited to adolescents in
      grades 7 through 12 of Mexican (n = 1657), Cuban (n = 490), Puerto Rican (n =
      555), and Central/South American or Dominican (C/S American or DR) (n = 427)
      origins. We used multivariate logistic regression for survey data to conduct the
      data analyses. RESULTS: Mexican-origin adolescents were less likely to report a
      routine physical examination in the previous year, compared with other Latino
      populations [prevalence (95% confidence interval)]: Mexicans, 47.7 % (42.0% 
      53.6%], Cubans 67.6% (57.4%-76.4%), Puerto Ricans 65.2% (58.4%-71.4%), and C/S
      American or DR (57.0% [47.3-66.2]). Among Mexican-origin adolescents, having a
      college-educated parent or insurance was associated with receiving care (adjusted
      prevalence odds ratio [95% confidence interval]), 2.12 (1.37-3.30) and 1.80 (1.31
      2.47), respectively. For Cuban-origin adolescents, first-generation immigrants
      were less likely to receive care (0.31 [0.14-0.70]), and those living in a single
      parent home were more likely to receive care (2.83 [1.52-5.25]). Having a routine
      physical examination among adolescents of C/S American or DR origins was
      associated with incomes above the poverty level (2.29 [1.10-4.77] and insurance
      (2.33 [1.10-4.91]). CONCLUSIONS: Reflecting the heterogeneity of Latino
      adolescents, the prevalence of routine physical examination and factors
      associated with it varied by national origin subgroup. These differences should
      be considered when developing strategies to better address the health needs of
      Latino youth.

PMID- 15450546
TI  - Adolescent sexual victimization, use of alcohol and other substances, and other
      health risk behaviors.
AB  - PURPOSE: To examine the relationship between substance use, other health risk
      behaviors, and sexual victimization among adolescent females. METHODS: A cross
      sectional telephone survey of 16-20-year-olds, including 647 female "ever
      drinkers" (1999) and 1236 female "never drinkers" and "ever drinkers" (2000) from
      17 states, was conducted as part of the National Evaluation of the Enforcing
      Underage Drinking Laws Program. The survey assessed underage alcohol use, sexual
      victimization, and other risky behaviors. Logistic regression modeling was used
      to measure the association among sexual victimization, substance use, and other
      risk behaviors. RESULTS: In 1999, 8.2% and in 2000, 7.1% of the participants
      reported having experienced actual or attempted sex against their will. Logistic
      regression analyses revealed that binge drinking in the past 2 weeks (1999), age
      at first drink (2000), sex without birth control (1999 and 2000), marijuana use
      in the past 30 days (1999 and 2000), and ever having been in a fight (2000) were
      associated with sexual victimization. CONCLUSIONS: Indicators of substance abuse
      and other health risk behaviors were strongly associated with sexual
      victimization among adolescent females. Implications for the direction of causal
      relationships are discussed.

PMID- 15450547
TI  - Emergency contraception use is correlated with increased condom use among
      adolescents: results from Mexico.
AB  - PURPOSE: To evaluate the association between knowledge about, or experience with,
      emergency contraception (EC), and condom use among school-attending adolescents
      in the state of Morelos, Mexico. METHODS: We analyzed data from anonymously self
      administered questionnaires (n = 10,918), from a cluster-randomized controlled
      trial among first year students from 40 (75%) public high schools in Morelos,
      Mexico. The survey included specific questions about EC knowledge and experience
      as well as questions about perceived ability to negotiate and condition sexual
      relations on condom use; and condom use at first and last sexual intercourse.
      RESULTS: Overall, 61% (6384) of students had heard of EC, and 36% (1964) of girls
      and 39% (1997) of boys had correct knowledge about EC. Correct knowledge was
      based upon knowing that EC is pills taken up to 3 days after unprotected sex to
      prevent pregnancy. Of 1695 (15.6%) reporting lifetime sexual activity, 16.4 %
      (275) reported they had tried to obtain EC and almost of all them (263) reported
      having used EC. The probability of a student reporting he/she is capable of
      interrupting sexual intercourse to use a condom was significantly higher for
      those who had correct EC knowledge, and a history of EC use was strongly
      correlated with condom use at last sexual intercourse. CONCLUSIONS: Experience
      with emergency contraception has no adverse effects on condom use, but rather is
      associated with an increased probability of condom use and an increased perceived
      capacity to negotiate condom use. Despite concern that information about, and
      access to EC may encourage sexual risk taking, our results suggest the reverse is
      true. These data support the position that there is no justification to withhold
      EC information or access from adolescents.

PMID- 15450554
TI  - Is no news good news? Organized follow-up, an absolute necessity for the
      evaluation of myocardial revascularization.
AB  - OBJECTIVE: The objective of this study is to find out whether follow-up
      information is registered by a non-organized follow-up representative for
      mortality and morbidity after myocardial revascularization. METHODS: The follow
      up information registered by an organized (OFU) and a non-organized (NOFU) follow
      up method is compared. The organized follow-up consists of an annual survey
      directly to the patient. The non-organized follow-up contains information
      provided by cardiologists and general practitioners. 1722 patients undergoing a
      CABG between 1999 and 2002 were included in this study. Completeness of the
      follow-up was registered as well as mortality and events, defined as return of
      angina, myocardial infarction, rhythm disturbances, heart failure, stroke and
      PTCA. RESULTS: The OFU was 98% complete and the NOFU 51.8% (P<0.05). The NOFU
      registered only 10 deaths; however, in the OFU another 21 patients who died
      during the first year postoperative were registered (P<0.05). In the OFU, 137
      patients were registered with an event and in the NOFU 53 (P<0.05). In NOFU, the
      mean was 108+/-91 days and median was 78 days. CONCLUSION: OFU improves the
      completeness of the follow-up, as expected, but informs superior about mortality
      and events. That in the NOFU, for 50% of the patients, the information is at the
      most 78 days postoperative old, let us suppose that a lot of early (6 months)
      postoperative information is even missed by an NOFU. The establishment of an
      organized follow-up and feedback of mortality and events after myocardial
      revascularization becomes indispensable.

PMID- 15450555
TI  - Surgical revascularization after acute myocardial infarction in patients with end
      stage renal disease.
AB  - OBJECTIVE: Cardiovascular disease accounts for over 50% of deaths in patients
      with end-stage renal disease (ESRD). After acute myocardial infarction (AMI),
      hospital mortality exceeds 25%, and survival beyond 2 years is <20% for patients
      with ERSD. The role of coronary artery bypass grating (CABG) in the setting of an
      AMI in patients with ESRD remains undefined. METHODS: Three hundred and forty-two
      patients had preoperative ESRD (serum creatinine >2.0mg/dl or dialysis
      dependence) between 1995 and 2000. One hundred and nineteen patients had an AMI
      (<7 days) and 223 patients had a remote myocardial infarction (RMI) (>7 days) at
      the time of CABG. The study group, AMI, was compared to the RMI group, which
      served as a comparison group. RESULTS: The age (69 vs. 67 years), males (68 vs.
      67%), creatinine (3.18 vs. 3.76 mg/dl, P=0.06), and preoperative dialysis (19 vs.
      22%, P=0.52) were similar in either the AMI or RMI group, respectively. The
      frequency of diabetes, hypertension, dyslipidemia, previous myocardial infarction
      were common, yet not different between groups (P=NS). For either AMI or RMI
      group, multivessel CABG (96 vs. 94%, P=0.73), off-pump CABG (OPCAB) (22 vs. 18%,
      P=0.67), and arterial conduits (71 vs. 78%, P=0.42) were similar. Among
      postoperative events, only pulmonary complications (33.8 vs. 14.7%, P=0.049) and
      atrial fibrillation (48 vs. 29%, P<0.001) were more common in the AMI group.
      Hospital mortality was no different between the AMI and RMI groups (10 vs. 8.5%,
      P=0.88). CONCLUSIONS: Although patients with ESRD that have an AMI or RMI
      represent high risk groups, perioperative outcomes suggest that patients selected
      for CABG as an early treatment strategy in the setting of an AMI represents a
      viable therapeutic option.

PMID- 15450556
TI  - Effect of cardiopulmonary bypass on cortical cerebral oxygenation during coronary
      artery bypass grafting.
AB  - OBJECTIVE: To investigate the changes in cerebral oxygenation during coronary
      artery bypass grafting (CABG) with normothermic cardiopulmonary bypass (CPB)
      using near infrared spectroscopy. METHODS: Measurement of cerebral cortical
      oxygenation changes included concentration of deoxygenated haemoglobin [HHb],
      oxygenated haemoglobin [O(2)Hb], changes in the redox status of the cytochrome c
      oxidase [Cyt-Ox], cerebral saturation as expressed by the tissue oxygenation
      index (TOI), and cerebral blood volume (CBV) as expressed by tissue haemoglobin
      index (THI). Measurements were performed in 19 consecutive patients undergoing
      normothermic (34-36 degrees C) CPB. Data were recorded at 0.5s intervals and
      averaged into 30 s epochs. Data analysis was carried at baseline, 1, 20, and 40
      min after start of CPB, at rewarming, on weaning from CPB, and at closing of
      chest. RESULTS: There were no in-hospital death, neurological deficits, or
      myocardial infarcts. Compared to baseline, during the entire CPB duration, there
      was a marked reduction in [O(2)Hb] and CBV which reached their worst level 40 min
      after initiation of CPB (from -3.03+/-5.1 to -9.25+/-7.20 micromol/l for
      [O(2)Hb], and a 24% reduction for CBV (both P<0.0001). The deterioration in
      [O(2)Hb] was recovered by the end of surgery, while the changes in CBV persisted.
      No significant changes occurred with respect to [HHb], [Cyt-Ox], and TOI.
      CONCLUSIONS: Conventional CABG is responsible for deterioration in [O(2)Hb], and
      CBV, which peak at 40-60 min following initiation of CPB. The changes in [O(2)Hb]
      are reversible whereas the reduction of CBV persists to the end of the surgery.
      This suggests a transient impairment in the autoregulatory mechanisms controlling
      cerebral blood flow following discontinuation of cardiopulmonary bypass.

PMID- 15450557
TI  - Coronary artery bypass grafting surgery is associated with a marked reduction in
      serum homocysteine and folate levels in the early postoperative period.
AB  - OBJECTIVE: It has been suggested that cardiac surgery-related ischemia
      reperfusion injury to the myocardium is caused by the oxidative stress, derived
      from the formation of reactive oxygen species in the early phases of the
      reperfusion. The availability of cysteine, mostly deriving from homocysteine
      (Hcy) via the trans-sulfuration pathway, is determinant for the synthesis of
      glutathione (GSH), which in turn acts as a first line of defence against
      oxidative stress. Indeed, an increased consumption of Hcy in response to
      oxidative stress has been described. Previous research has shown that Hcy levels
      increase during the first weeks or months after coronary artery bypass grafting
      (CABG). This study was designed to evaluate the Hcy metabolism in CABG patients
      during the early postoperative period. METHODS: Serum Hcy and folate were
      measured by an automatic immunometric system on blood samples obtained from 48
      (mean age 67+/-10 years) consecutive patients undergoing CABG, preoperatively and
      at 0, 12, 48, and 120 h after surgery. A subgroup of 22 of these patients was
      also studied 6 months postoperatively. RESULTS: A significant decrement of Hcy
      and folate was observed throughout the study (P<0.0001) from 17.3+/-9.3 to 8.5+/
      5.6 micromol/l at 12 h postoperatively for Hcy, and from 5.1+/-2.8 to 2.5+/-1.5
      ng/ml at 48 h for folate. The reduction of Hcy and folate levels remained
      significant after correction for haemodilution (as assessed by measurement of
      plasma proteins). Furthermore, the use of cardiopulmonary bypass significantly
      interacted with the time of sampling in affecting the Hcy levels. Hcy levels
      returned to near-baseline values 48 h postoperatively, and were similar to base
      line at follow-up. CONCLUSION: Our study indicates that serum Hcy and folate
      levels are markedly reduced during the early postoperative period after CABG.
      This reduction is at least in part independent of haemodilution, and may be
      caused by an altered Hcy turnover, due to an increased consumption of GSH during
      and soon after CABG.

PMID- 15450558
TI  - Efficacy of pre-emptive milrinone in off-pump coronary artery bypass surgery:
      comparison between patients with a low and normal pre-graft cardiac index.
AB  - OBJECTIVE: The effect of pre-emptive milrinone without bolus during off-pump
      coronary artery bypass surgery (OPCAB) was evaluated in two groups of patients
      with low and normal pre-graft cardiac index. METHODS: Eighty-two patients were
      divided into two groups based on their pre-graft cardiac index. Each group was
      randomly subdivided into two groups to receive either milrinone or normal saline.
      After the internal mammary artery was harvested, the infusion of milrinone, or
      normal saline was started and maintained until the end of the anastomosis. The
      haemodynamic variables were measured: just before the start of milrinone or
      normal saline after pericardiotomy (baseline value); 10 min after the tissue
      stabilizer had been applied for the anastomosis of left anterior descending
      artery, left circumflex artery and right coronary artery; and after the sternal
      closure. RESULTS: Milrinone reduced the extent of the decrease in cardiac index
      and stroke volume as well as the extent of the increase in systemic and pulmonary
      vascular resistance. The extent of the decrease in cardiac index and mixed venous
      oxygen saturation were greater in normal pre-graft cardiac index group than in
      low pre-graft cardiac index group regardless of milrinone infusion during
      anastomoses. The effect of milrinone on haemodynamics showed no significant
      difference between low and normal pre-graft cardiac index groups. CONCLUSIONS:
      Pre-emptive milrinone infusion without bolus effectively improved cardiac
      performance during OPCAB and was especially useful for patients with low pre
      graft cardiac index to prevent the decrease in cardiac index and stroke volume
      index below the critical level.

PMID- 15450559
TI  - Postoperative naproxen after coronary artery bypass surgery: a double-blind
      randomized controlled trial.
AB  - OBJECTIVE: Non-steroidal anti-inflammatory drugs (NSAIDs) are routinely used
      after coronary artery bypass surgery (CABG), yet their effects have seldom been
      evaluated in randomized controlled settings. The aim of this study was to examine
      the efficacy and safety of a commonly used NSAID, naproxen. We hypothesized that
      naproxen would reduce postoperative pain following CABG without increasing
      complications. METHODS: Patients (N=98) undergoing primary CABG were randomized
      to receive naproxen (500 mg q12hX5 doses via suppository started 1h after
      operation, followed by oral 250 mg q8hX6 doses) or placebo. Standard analgesic
      and anti-emetic regimens were available to both patient groups. Interventions
      were double-blinded. Primary end-points were postoperative pain measured before
      and after chest physiotherapy by visual analog scale and pulmonary slow vital
      capacity (SVC). RESULTS: Baseline characteristics were equivalent between the two
      groups. Over the first 4 postoperative days, naproxen decreased pain by 47+/-17%
      on average before chest physiotherapy (P=0.034), and 44+/-13% after chest
      physiotherapy (P=0.0092). Patients who received naproxen also had better
      preservation of SVC over the first 4 postoperative days (mean loss of SVC from
      baseline: 2.1+/-0.1 vs. 2.5+/-0.1l, naproxen vs. placebo, P=0.0032). This was
      concomitant with a lower white blood cell count observed in naproxen patients
      (9.2+/-0.3 vs. 12.7+/-1.5x10(9)/l, naproxen vs. placebo, P=0.03). Patients who
      received naproxen had more chest tube drainage after 4h postoperatively, but
      there was no difference in the incidence or amount of transfusions. There was no
      difference in medication use, length of stay, or in the incidence of atrial
      fibrillation, azotemia, and other complications. CONCLUSIONS: Naproxen is an
      effective and low-cost adjunct for optimization of pain control and lung recovery
      after CABG. Its use may result in increased chest tube drainage, but no apparent
      increase in other complications.

PMID- 15450560
TI  - Does off-pump coronary artery bypass reduce the incidence of post-operative
      atrial fibrillation? A question revisited.
AB  - Atrial fibrillation (AF) is the most common post-operative complication in
      patients undergoing coronary artery bypass grafting, with an increased incidence
      associated with advancing age. This study aims to determine whether off-pump
      coronary artery bypass (OPCAB) reduces the incidence of AF in a generalized
      population (mean age <70 years). A meta-analysis was performed including all
      randomised and propensity score matched non-randomised studies published between
      2001 and 2003 reporting a comparison between the two techniques in a generalised
      patient group (average age <70 years). The primary outcome of interest was post
      operative AF. Sensitivity analysis was performed to evaluate consistency of the
      calculated treatment effect. Fourteen studies fulfilled our inclusion criteria,
      including a total of 16,505 subjects. The incidence of AF was 19% (1612/8265) in
      the off-pump group versus 24% (1976/8240) in the on-pump group. When considering
      only the 11 randomised studies (2207 subjects), we found a significant reduction
      in the incidence of post-operative AF in the off-pump group using a random-effect
      model (odds ratio (OR)=0.60, 95% confidence interval (CI)=0.45-0.82, and chi
      square of heterogeneity=18.02, P=0.05). Sensitivity analysis highlighted one
      randomised study causing funnel plot asymmetry, exclusion of which resulted in a
      significant reduction in the incidence of post-operative AF in the off-pump group
      (OR=0.71, 95% CI=0.57-0.90), with a non-significant heterogeneity of 3.91
      (P=0.92). When only studies of high quality were considered (898 patients), no
      significant difference was seen between on and off-pump groups (OR=0.78, 95%
      CI=0.57-1.07, and heterogeneity=0.53, P=0.91). This may be due to small number of
      patients in this group. Our results suggest that although OPCAB surgery may
      reduce the incidence of post-operative AF in a generalised population (age <70
      years) this finding is not clearly supported by high quality randomised trials.
      Although previous evidence suggests that the incidence of post-operative AF is
      reduced in an elderly population (>70 years) with off-pump surgery, our results
      show that the evidence is less clear in a younger population group. The question
      of whether off-pump surgery in this patient group results in a lower rate of post
      operative AF remains to be answered by further high quality randomised research.

PMID- 15450561
TI  - Electromechanical left ventricular resynchronisation by coronary artery bypass
      surgery.
AB  - OBJECTIVE: In patients with coronary artery disease (CAD), the normal
      electromechanical response to dobutamine stress is deranged: QRS duration
      lengthens rather than shortens, left ventricular asynchrony develops, post
      ejection shortening appears, and total isovolumic time (the time in the cardiac
      cycle when the ventricle is neither ejecting nor filling) increases rather than
      falls, all of which blunt the normal rise in cardiac output. We aimed to study
      the effect of revascularisation on these stress-induced electromechanical
      abnormalities and their effect on peak cardiac output after coronary artery
      bypass grafting (CABG). METHOD: 20 unselected patients were studied before and
      after CABG. Long axis asynchrony was determined by (i) delay in the onset of
      shortening, (ii) amplitude and (iii) duration of post-ejection shortening. Total
      isovolumic time (in s/min), calculated as [60-(total ejection time+total filling
      time)] and cardiac output were measured by Doppler echocardiography. RESULTS:
      Before CABG: QRS duration broadened with stress (by 7+/-8 ms, P<0.01) and post
      ejection shortening increased (amplitude by 1.1+/-0.7 mm, P<0.01, duration by 8+/
      9 ms, P<0.01). Total isovolumic time increased (by 3+/-3 s/min, P<0.01) and
      cardiac output rose (by 2.8+/-1.2 l/min, P<0.01). After CABG: QRS duration
      shortened with stress (by 5+/-4 ms, P<0.01) post-ejection shortening decreased
      (amplitude and duration fell by 0.4+/-0.5 mm and 22+/-14 ms, respectively), total
      isovolumic time shortened (by 3+/-3 s/min) and cardiac output increased (by 5.1+/
      1.8 l/min, all P<0.01). Changes in total isovolumic time and duration of post
      ejection shortening with stress were independent predictors of the increase in
      peak cardiac output after revascularisation (total R(2)=0.69). Independent
      predictors of changes in total isovolumic time with stress were those in QRS
      duration and the duration of post-ejection shortening (total R(2)=0.75). In turn,
      changes in the duration of post-ejection shortening were closely associated with
      alterations in the delay in long axis shortening (r(2)=0.50) which correlated
      with changes in QRS duration (r(2)=0.59, all P<0.001). CONCLUSIONS:
      Revascularisation resynchronises left ventricular wall motion by restoring the
      normal activation response to stress, thereby reducing total isovolumic time and
      normalising peak cardiac output response to stress.

PMID- 15450562
TI  - Oral thyroid hormone pretreatment in left ventricular dysfunction.
AB  - OBJECTIVE: The aim of the present study was to determine whether pretreatment
      with oral thyroid hormone had beneficial effects in cardiac function and
      morbidity and mortality after cardiac operations. METHODS: Eighty patients
      undergoing coronary artery bypass grafting with a preoperative left ventricular
      ejection fraction (LVEF) less than 30% scheduled for elective coronary bypass
      grafting agreed to participate in this prospective, randomized trial. The
      triiodothyronine (T(3)) (Group I) and control groups (Group II) were equally
      divided. Patients randomized to the T(3) group received T(3) 125 microg/day
      orally for 7 days preoperatively and from the first postoperative day till the
      discharge. Outcome variables included perioperative hemodynamic data, inotropic
      requirements, morbidity and mortality. Hemodynamic data were collected before
      induction of anesthesia and following every 4 h. The thyroid profile was
      determined upon admission, after the induction of anesthesia, 5 min after the
      start of cardiopulmonary bypass (CPB) and after hourly intervals and after 24th
      hour, at 24h intervals till the 120th hour. RESULTS: There were 6 deaths, three
      in each group. Patients in the T(3) group demonstrated a higher cardiac index
      than patients in the placebo group in the entire post-CPB periods (P<0.01). Mean
      inotropic requirements remained lower in the T(3) group than in the placebo group
      (P<0.001). CONCLUSIONS: Although our study stresses the benefits of oral T(3)
      administration on the hemodynamic and prognostic parameters in patients with
      impaired left ventricular function and undergoing CABG weakly, it may warrant
      further much larger scaled studies that can reach statistical significance.

PMID- 15450563
TI  - Muscular counterpulsation: preliminary results of a non-invasive alternative to
      intra-aortic balloon pump.
AB  - OBJECTIVES: IABP is the most widely used form of temporary cardiac assist and its
      benefits are well established. We designed an animal study to evaluate a device
      based on muscular counterpulsation (MCP) that should reproduce the same
      hemodynamic effects as IABP in a completely non-invasive way. METHODS: Six
      calves, 60+/-4 kg, divided into 2 groups, in general anaesthesia, equipped with
      EKG, Swan-Ganz, pressure probe in the femoral artery and flow probe in the left
      carotid artery, received either IABP through right femoral artery, or muscle
      counterpulsation (MCP). MCP consists of electrically induced skeletal muscle
      contraction during early diastole, triggered by EKG and microprocessor controlled
      by a portable device. For each animal the following parameters were also
      considered: mean aortic pressure (mAoP), CO, CI, left ventricular stroke work
      index (LVSWI), systemic vascular resistance (SVR) and mean femoral artery flow
      (Faf). We did 3 sets of measurements: baseline (BL), after 20 (M20) and 40 (M40)
      min of cardiac assistance. These measurements have been repeated after 40 min of
      rest for 3 times. Results are expressed as mean+/-SD. RESULTS: Baseline values:
      mAoP, 76.51+/-12 mmHg; mCVP, 11.5+/-3 mmHg; CO, 5+/-1 l/min per m(2); LVSWI,
      0.77+/-0.2 KJ/m(2); SVR, 1040+/-15 dyns/cm(-5); Faf, 75.5+/-10 ml/min. IABP
      group: mAoP, 81.1+/-6 mmHg; mCVP, 1+/-0.1 mmHg; CO, 4.5+/-0.7 l/min per m(2);
      LVSWI, 0.69+/-0.2 KJ/m(2); SVR, 1424+/-8 dyns/cm(-5); Faf, 64.3+/-3 ml/min. MCP
      group: mAoP, 60.1+/-7 mmHg; mCVP, 23.6+/-2 mmHg; CO, 4.8+/-0.4 l/min per m(2);
      LVSWI, 0.69+/-0.2 KJ/m(2); SVR, 608+/-25 dyns/cm(-5); Faf, 92.3+/-12 ml/min.
      CONCLUSIONS: MCP and IABP had the same effects on CO and LVSWI. Moreover, MCP
      reduced SVR and increased the peripheral circulation without requiring any
      vascular access nor anticoagulation therapy.

PMID- 15450564
TI  - Clinical situations demanding weaning from long-term ventricular assist devices.
AB  - OBJECTIVE: Ventricular assist devices are increasingly used to treat patients
      with acute or chronic end-stage heart failure. We report on circumstances,
      exemplified on four cases, where a surprisingly favorable clinical course of the
      patients ultimately demanded early explantation of the device, which was not
      anticipated prior to its implantation. METHODS: The four patients were provided
      with implantable (Micromed BeBakey trade mark, Incor trade mark ) and external
      pneumatically driven (Thoratec trade mark, Excor trade mark ) devices under
      emergency conditions and were listed for heart transplantation. RESULTS: All four
      patients had an unexpected recovery of myocardial pump function. After careful
      diagnostic evaluation, all device components were completely removed without
      extracorporeal circulation. No stepwise weaning protocol was employed.
      CONCLUSIONS: Weaning patients from ventricular assist devices after recovery of
      myocardial pump function can become necessary. Diagnostic evaluation and the
      implementation of a weaning protocol is still a matter of debate, while complete
      surgical removal of all device components without extracorporeal circulation is
      possible with a low risk.

PMID- 15450565
TI  - Sympathetic reinnervation after heart transplantation, assessed by iodine-123
      metaiodobenzylguanidine imaging, and heart rate variability.
AB  - OBJECTIVE: Complete allograft denervation occurs during heart transplantation.
      Partial ventricular sympathetic reinnervation may develop one year or later after
      transplantation and can be measured with iodine-123-meta-iodobenziylguanidine
      (MIBG) uptake. Aim of this study was to assess sinus node sympathetic
      reinnervation measured with heart rate variability and ventricular sympathetic
      reinnervation evaluated with MIBG. METHODS: Twelve patients and 14 healthy
      controls were included. In patients, MIBG scintigraphy with early and late
      imaging was performed. Heart to mediastinum ratio (HMR) was calculated and
      patients were divided in groups with (HMR>1.3) and without left ventricular
      reinnervation (HMR<1.3). Bipolar ECG with high sampling rate and resolution was
      recorded over 8.5 min in supine position and in upright position after 10 min
      interval. R-R intervals in time domain and heart rate variability in frequency
      domain through spectral power analysis of R-R intervals were analysed to evaluate
      sinus node reinnervation. Spectral power in low frequency range (0.04-0.15 Hz)
      above 4.5 ms(2) was considered as sinus node sympathetic reinnervation. RESULTS:
      Six (50%) patients had evidence of left ventricular sympathetic reinnervation on
      scintigraphy. Sinus node sympathetic reinnervation based on heart rate
      variability was detected in 6 (50%) patients in supine, and in 4 (33%) patients
      in upright body position. Four patients groups were discerned: (1) with
      ventricular and sinus node sympathetic reinnervation, (2) with sinus node
      sympathetic reinnervation, (3) with ventricular sympathetic reinnervation and (4)
      without atrial or ventricular sympathetic reinnervation. Ventricular
      reinnervation process was time dependent and sinus node reinnervation was not.
      CONCLUSIONS: Simultaneous ventricular sympathetic reinnervation assessed by MIBG
      and sinus node sympathetic reinnervation assessed by heart rate variability in
      supine as in upright position were detected only in two patients (17%). The
      results of our study show that eventual sinus node sympathetic reinnervation and
      left ventricular sympathetic reinnervation do not occur simultaneously.

PMID- 15450566
TI  - Microwave ablation for the surgical treatment of permanent atrial fibrillation--a
      single centre experience.
AB  - OBJECTIVE: Microwave ablation (MW) has been established as a safe and efficient
      procedure for the treatment of permanent atrial fibrillation (pAF) resulting in
      conversion to sinus rhythm (SR). For further improvement of clinical results, a
      new ablation line concept has been introduced. We present the first clinical
      results using this new concept in comparison with the results of previous
      ablation line concepts. METHODS: Ablation lines were performed using microwave
      energy (Flex 2 and Flex 4 device). We compared two groups, including patients
      (pts) with mitral valve disease (MVD), coronary artery disease (CAD), and aortic
      valve disease (AVD). Group A included 137 patients, age 68.4+/-7.8, with ejection
      fraction 32-80%, left atrial diameter 52.6+/-9.6 mm, suffering from MVD (n=87),
      CAD (n=59) or AVD (n=36) with pAF for 6.5+/-9.2 years using the original ablation
      line concept. Group B included 112 patients, age 68.1+/-8.0, ejection fraction 20
      83%, left atrial diameter 53.1+/-8.7 mm with pAF for 6.8+/-7.0 years suffering
      from MVD (n=72), CAD (n=33) or AVD (n=36) performing a modified ablation line.
      RESULTS: Survival rate of group A was 98.5% and 97.3% in group B. In the 6-month
      follow-up for group A, 62% of patients with MVD, 68% with CAD and 78% with AVD
      were in SR. For group B, 88% of patients with MVD, 78% with CAD and 85% with AVD
      were in SR. CONCLUSIONS: MW has become an efficient option with an excellent
      benefit/risk ratio for the treatment of pAF in patients with other cardio
      surgical disease. The modified ablation line concept in association with the
      introduction of a new ablation catheter resulted in a 10% higher success rate.
      Therefore we have established this new lesion line concept as our standard for
      microwave ablation.

PMID- 15450567
TI  - Influence of bileaflet prosthetic mitral valve orientation on left ventricular
      flow--an experimental in vivo magnetic resonance imaging study.
AB  - OBJECTIVE: Orientation-related bileaflet mechanical valve flow and velocity
      studies in the downstream area are limited in mitral valve replacement studies.
      METHODS: In five sheep, ventricular blood flow was visualized prior to the
      implantation of a mitral Edwards Mira Bileaflet Mechanical Valve Model 9600. The
      implant orientation was either anatomic, with a 45 degrees rotation, or anti
      anatomic, with a 90 degrees rotation. Sheep were positioned within an 1.5T field
      strength MR scanner (Magnetom Sonata; Siemens) to assess time-dependent three
      dimensional blood flow velocities displayed as color-encoded vectors. RESULTS:
      The preoperative ventricular velocity profiles presented negligible individual
      variances. Streamlines passed homogeneously without any spatial differences into
      the left ventricle. Starting from the anatomical position, the areas with
      inhomogeneous and accelerated local blood velocities increased in comparison to
      the preoperative status. Rotating the prosthesis until it was in a 45 degrees
      position caused a significant increase in turbulence immediately downstream;
      fluids stagnated longer at the apex. In the anti-anatomic orientation, mean
      velocities decreased. In all three positions, but less so in the anatomical
      position, the flow pattern of the blood helix at the apex was disturbed. The
      intraventricular flow patterns between prostheses in the three orientations were,
      however, not significant when compared to the differences between physiologic
      intraventricular flow and any of the postoperative measurements. CONCLUSIONS: To
      achieve optimal hemodynamics, rotation of the mitral valve has to be considered
      carefully, as has long been known from aortic valve replacement studies. To this
      end, a method for qualitative assessment of left ventricular blood flow patterns
      was developed.

PMID- 15450568
TI  - The left atrioventricular valve in partial atrioventricular septal defect:
      management strategy and surgical outcome.
AB  - OBJECTIVE: To test the hypothesis that in patients with a partial
      atrioventricular septal defect (PAVSD) and a competent left atrioventricular
      valve (LAVV), sutures should be placed across the line of apposition of the
      superior and inferior bridging leaflets, septal commissure (SC), to prevent the
      development of regurgitation. Outcome of surgery and risk factors for the need
      for LAVV reoperation of patients with mild or no LAVV regurgitation (LAVVR) were
      evaluated. BACKGROUND: Controversy over management of the LAVV in PAVSD. METHOD:
      One hundred and forty seven children with PAVSD underwent surgical repair at the
      Royal Brompton Hospital between January 1983 and December 1999. Of this group, 21
      (16.7%) had LAVVR of sufficient severity to require surgical intervention and
      were therefore excluded from analysis. The median age and weight at repair of
      those with mild or no LAVVR was 4.1 years and 15.4 kg. One hundred and eight had
      normal chromosomes, 13 Down syndrome and five other syndromes. The interatrial
      communication was closed using a pericardial patch in 62.7% and with synthetic
      material in the remainder. Intraoperative testing of LAVV competence was
      undertaken using saline injection into the left ventricle. In 80.9%, sutures were
      placed across the line of apposition of the left sided superior and inferior
      bridging leaflets partially to close the SC (sometimes incorrectly named the
      mitral valve cleft). RESULT: The overall hospital mortality was 3.2% (95%
      confidence interval (CI) 1, 8.4%), which did not differ statistically in the last
      20 years. No specific risk factors for early death were identified. Eleven
      patients (8.7%, 95% CI 4.7, 15.4%) required reoperation, 10 for LAVV repair and 1
      resection of subaortic stenosis. Univariate analysis of risk factors for LAVV
      reoperation were low weight, relatively small size LAVV, the presence of a small
      preoperative interventricular interchordal communication and duration of
      ventilation. Ten (9.8%) of 102 patients in whom SC was sutured required LAVV
      reoperation but none for 24 in whom the commissure was left alone. CONCLUSION:
      The hypothesis that in the absence of preoperative LAVVR it is necessary to place
      sutures in the SC has not been proven. We consider that in addition to
      preoperative cross sectional echocardiographic assessment of LAVVR intraoperative
      evaluation of LAVV function allows discrimination between those valves where
      sutures to the septal commissure are necessary and those where the valve can be
      left undisturbed.

PMID- 15450569
TI  - Ascending aortic origin of a branch pulmonary artery--surgical management and
      long-term outcome.
AB  - OBJECTIVE: Ascending aortic origin of a branch pulmonary artery (AOPA,
      hemitruncus arteriosus) is a rare congenital malformation. While there have been
      isolated case reports, larger series, relating to long-term outcomes following
      surgery are few. This article analyses the surgical results of a series of nine
      patients, over a period of 29 years. METHODS: Between 1974 and 2003, nine
      patients [neonates, 6; infants, 3; male, 5; female, 4] were operated on for AOPA.
      Median age at presentation was 14 days (range birth to 231 days). Six [corrected]
      patients (group 1) had associated simple lesions like patent ductus arteriosus or
      right aortic arch. Three patients (group 2) had complex lesions with right
      ventricular outflow tract obstruction. One patient (group 2) had DiGeorge
      syndrome. All patients except group 2 presented with congestive cardiac failure
      and, in addition one had pre-operative coronary ischemia. Diagnosis was
      established by angiocardiography in two patients and by echocardiography in seven
      [corrected] The median age at operation was 28 days (range 7-365). Follow-up
      period ranged from 7 months to 20.5 years (median 9 years). RESULTS: All nine
      patients had an anomalous right pulmonary artery (RPA) arising from the proximal
      ascending aorta, while the left branch was of right ventricular origin. All had
      evidence of pulmonary hypertension or elevated right ventricular pressure pre
      operatively. There was no operative mortality. Of eight patients who had direct
      anastomosis of the RPA to the main pulmonary artery, one required patch
      enlargement and another required stenting of an anastomotic stenosis. One patient
      had a RV-RPA conduit, which required replacement 8, 13, and 14 years later. At
      follow-up, all patients were alive. All patients in group 1 had normal
      haemodynamic function and were in NYHA class I. In group 2, all were in NYHA
      class II with evidence of right ventricular hypertrophy. Four patients had post
      operative ventilation-perfusion scans which showed satisfactory perfusion to both
      lungs. CONCLUSIONS: Early surgery is indicated in this lesion and is compatible
      with good long-term outlook. Surgical repair should not be deferred for
      corrective procedures of associated cardiac anomalies.

PMID- 15450570
TI  - Functional biventricular repair using left ventricle-pulmonary artery conduit in
      patients with discordant atrioventricular connections and pulmonary outflow tract
      obstruction-does conduit obstruction maintain tricuspid valve function?
AB  - OBJECTIVE: The aim of the study is to determine whether function of the tricuspid
      valve placed for the systemic circulation is related to left ventricular pressure
      supporting the pulmonary circulation after functional repair for atrioventricular
      discordance. METHODS: Right ventricular volume and tricuspid regurgitation (TR)
      were investigated, in relation to left ventricular pressure, in 15 patients with
      this malformation who underwent functional biventricular repair with left
      ventricle-pulmonary artery conduit. RESULTS: After the functional biventricular
      repair, ratio of systolic left ventricular pressure to right ventricular one
      (LVP/RVP) was 0.58+/-0.24 and right ventricular end-diastolic pressure (RVEDV)
      significantly increased from 104+/-24 to 137+/-39% of normal predicted value (P =
      0.015). Five patients with LVP/RVP>0.6 were free from TR, however, six of seven
      with LVP/RVP<0.6 developed TR. Three patients required eventual tricupid valve
      replacement. Conduit replacement was required in seven patients and five were
      assessed similarly. After the conduit replacement, LVP/RVP decreased from 1.08+/
      0.34 to 0.58+/-0.14 and RVEDV increased significantly from 87+/-24 to 129+/-19%
      (P = 0.011). One patient with postoperative LVP/RVP of 0.36 developed moderate
      TR. CONCLUSION: Mild obstruction at the pulmonary channel is not necessarily an
      evil after functional biventricular repair for this malformation, in terms of TR
      and right ventricular dilatation.

PMID- 15450571
TI  - Vocal cord palsy as a complication of adult cardiac surgery: surgical
      correlations and analysis.
AB  - Vocal cord palsy after adult cardiac surgery is often attributed to non-surgical
      mechanisms as tracheal intubation and central venous catheterisation. It may also
      be caused by injury of the recurrent laryngeal nerves by surgical dissection. We
      hereby present a review of relevant clinical reports. The cumulative incidence
      was 1.1% (33 in 2980). Main reported surgical mechanisms of injury were
      harvesting of internal thoracic artery and topical cold cardioprotection.
      Bilateral nerve palsy has been lethal on at least one occasion. Where vocal cord
      injury followed harvesting of the left internal thoracic artery, it was reported
      ipsilateral to the conduit.

PMID- 15450572
TI  - Reverse cardiac remodelling in patients with primary pulmonary hypertension after
      isolated lung transplantation.
AB  - OBJECTIVE: Pulmonary hypertension eventually leads to severe distortion of the
      cardiac geometry with consequent impact on cardiac function. The purpose of this
      study was to prove reverse cardiac remodelling after isolated bilateral lung
      transplantation (LuTX) in patients with advanced primary pulmonary hypertension
      (PPH) and severe alterations of cardiac morphology and function. METHODS: In the
      period of 2000-2002 17 (10 female, seven male) patients with advanced PPH
      underwent isolated bilateral LuTX. Median age was 30 years (range 16-53). All
      patients were in NYHA III or IV, most of them with intractable ascites,
      established renal impairment, malnutrition and immobility, continuously
      deteriorating despite various forms of pharmacological treatment including i.v.
      and inhalative prostacyclin, diuretics, Ca-antagonists, bosentan and
      catecholamines. Echocardiography and Doppler echocardiography measurements were
      performed before and 3 months after transplantation. Left and right ventricular
      diameters and function were assessed and tricuspid valve regurgitation was
      determined. RESULTS: Mortality after 3 months was 17.5% (cerebral bleeding, multi
      organ failure and diffuse myocardial infarction in one patient each). Three
      months after LuTX the 14 surviving patients were in NYHA I or II.
      Echocardiography showed normal left ventricular function and markedly improved
      right ventricular function with normal size of the RV. The leftward shifted
      flattened interventricular septum had returned in its physiological position and
      the high-grade tricuspid insufficiency had disappeared in all patients.
      CONCLUSIONS: Advanced alterations of cardiac morphology and function normalize
      completely and pre-existing tricuspid insufficiency disappears in PPH patients
      after isolated bilateral LuTX. Quality of life is excellent. Therefore, LuTX is
      preferred and safe in patients with advanced PPH even with severe cardiac
      dysfunction.

PMID- 15450573
TI  - Small cell lung cancer in Norway. Should more patients have been offered surgical
      therapy?
AB  - OBJECTIVE: The final outcome of patients with small cell lung cancer (SCLC) is
      poor with an overall 5-year survival rate of less than 10%. Therefore, the
      question of surgery in patients with a technically-operable solitary tumor has
      been raised. The purpose of this study was to identify the proportion of patients
      with operable SCLC and to assess the prognosis of different treatment strategies.
      For patients who were operated, we compared the resection specimens from patients
      with more than 5-year survival with those with shorter survival to see whether
      the specimens belonged to different subclasses of SCLC. METHODS: In Norway all
      clinical and pathologic departments submit reports on cancer patients to the
      Cancer Registry. The Registry also has a law-regulated authority to collect
      supplemental information regarding diagnosis, treatment and outcome for all
      cancer patients from the hospitals in charge. All reports on patients diagnosed
      as having SCLC in limited disease or unknown stage during the time interval 1993
      1999 were reviewed. Patients with a T2-tumor, in whom a pneumonectomy would have
      to be performed, were classified as potentially operable. Five-year relative
      survival was calculated for patients diagnosed in 1993-1997. RESULTS: During the
      actual period 2442 individuals with SCLC were identified. The majority was
      treated with conventional chemotherapy or concurrent chemoradiotherapy while 38
      underwent surgical therapy. Following reclassification of 697 patients reported
      to have limited disease or unknown stage 180 were judged to be in stage I. In
      addition to the 38 resected patients 14 were considered fit for surgery
      technically and medically while 97 were found to be potentially operable
      treatment modalities apart from surgery yielded a 5-year survival rate <7%. For
      stage I (N=96) the rate was 11.3% in conventionally treated patients compared to
      44.9% for those who underwent surgical resection. By pathological review of
      surgical specimens a diagnosis of SCLC was confirmed in all patients treated by
      surgery in the groups with long and short survival. CONCLUSION: This
      investigation demonstrates that patients with SCLC having a peripherally located
      tumor should be referred to surgery, as long time survival is far better than for
      conventionally treated patients.

PMID- 15450574
TI  - Preoperative chemotherapy increases cytokine production after lung cancer
      surgery.
AB  - OBJECTIVE: Many phase II trials have shown that preoperative chemotherapy for
      lung cancer is feasible but associated with postoperative morbidity and
      mortality. However, little is known about the effect of preoperative chemotherapy
      on surgical stress and postoperative complications associated with surgical
      intervention. We evaluated the effect of preoperative chemotherapy on
      perioperative inflammatory cytokine production as a surgical stress marker.
      METHODS: The study group comprised 38 patients undergoing anatomical lung
      resection and mediastinal nodal dissection for clinical stage IB/II non-small
      cell lung cancer during the period October 2001-December 2003. Nineteen patients
      received a single cycle of cisplatin (80 mg/m(2)) and docetaxel (60 mg/m(2))
      chemotherapy prior to surgery (neoadjuvant group), and 19 patients underwent
      surgery without any previous chemotherapy (control group). White blood cell and
      neutrophil counts and serum concentrations of C-reactive protein (CRP),
      interleukin-6 (IL-6), and granulocyte colony-stimulating factor (GCSF) were
      determined before surgery and on postoperative days 1 and 3. Postoperative
      complications were reviewed. Differences were assessed by repeated analysis of
      variance. RESULTS: Serum concentrations of IL-6 and GCSF rose significantly on
      postoperative days 1 and 3 in the neoadjuvant group in comparison to
      concentrations in the control group, but white blood cell count, neutrophil
      count, and CRP did not differ between the groups. No major complication occurred
      in either group. CONCLUSIONS: A single cycle of cisplatin and docetaxel
      chemotherapy followed by surgery can exacerbate overproduction of inflammatory
      cytokines during the perioperative period in lung cancer patients.

PMID- 15450575
TI  - Evaluation of isolated lung perfusion as neoadjuvant therapy of lung metastases
      using a novel in vivo pig model: I. Influence of perfusion pressure and
      hyperthermia on functional and morphological lung integrity.
AB  - OBJECTIVE: Despite favorable experimental results and an encouraging early
      experience in humans, isolated lung perfusion (ILP) for treatment of metastases
      is still not established clinically. The complexity of the procedure as well as
      poor knowledge regarding the technical necessities of lung perfusion represents
      major limitations. METHODS: In this novel in vivo pig model, ILP of the left lung
      was performed for 40 min followed by the exclusion of the right lung. Survival
      and all monitored parameters of hemodynamics, ventilation and gas exchange were
      exclusively dependent on the previously perfused left lung for the 6-h
      reperfusion period. Furthermore, histological examination was assessed. In the
      first protocol influence of different perfusion pressures (PP) on the native lung
      tissue was investigated (LPG, n=6, PP<25 mmHg; HPG, n = 8, PP> or =25 mmHg). In
      the second protocol the influence of normothermic (T-38; n=5; t=38 degrees C),
      mild (T-40; n=5; t=40 degrees C) and moderate hyperthermic (T-41.5; n=5; t=41.5
      degrees C) perfusion temperature was evaluated. Results were compared to those of
      a sham-operated control group (SG, n=5). RESULTS: ILP led to a slight
      deterioration of all functional as well as histological parameters in all groups.
      HPG resulted in impairment regarding all monitored parameters compared to LPG and
      SG. Significant differences between HPG and SG were found for cardiac index
      (P=0.026) and pulmonary vascular resistance index (PVRI, P=0.026). Histological
      scoring revealed significantly higher grade of lung injury for HPG animals
      (P=0.001). Functional parameters did not differ between normothermic and
      hyperthermic perfusion groups. However, animals of the T-38 group demonstrated
      significantly increased PVRI (P=0.004). Histological examination revealed
      significantly higher scores of acute lung injury for all perfusion groups
      compared to the Sham group (P<0.001). CONCLUSIONS: The results of this novel
      large animal model represent the first available demonstration that increased PP
      in a setting of ILP will result in deleterious effects on lung function and
      morphology. However, mild to moderate hyperthermia is well tolerated by the
      native lung tissue.

PMID- 15450576
TI  - Evaluation of isolated lung perfusion as neoadjuvant therapy of lung metastases
      using a novel in vivo pig model: II. High-dose cisplatin is well tolerated by the
      native lung tissue.
AB  - OBJECTIVE: Efficacy of in vivo isolated lung perfusion (ILP) with cisplatin could
      be shown in different rodent tumor models. Despite the use of this alternative
      therapeutical strategy in very few patients with lung metastases, there are no
      systematic studies regarding the tolerance of the native lung tissue in large
      animal models or humans. METHODS: In a novel ILP pig model, groups with two
      different concentrations of cisplatin (group CP150: 150 mg/m(2) cisplatin, n=5;
      group CP300: 300 mg/m(2) cisplatin, n=5) were compared with a control group (n=5)
      and a Sham group (n=5) concerning the influence on hemodynamic, ventilatory and
      gas exchange parameters as well as on structural integrity of the lung. In the
      additional CP300-HT group the potentially cumulative effect of hyperthermia and
      high-dose cisplatin perfusion was evaluated (300 mg/m(2) cisplatin, 41.5 degrees
      C, n=5). Following the ILP of the left lung for 40 min, right main bronchus and
      right pulmonary arteries were clamped and survival as well as lung function
      parameters were dependent on the previously perfused lung for the 6-h-reperfusion
      period. Quantification of histological acute lung injury was performed using the
      score of Chiang. ANOVA, ANOVA with repeated measures and Pearson's correlation
      estimation were applied for statistical evaluation. RESULTS: All animals survived
      ILP and the entire reperfusion period. Platinum levels of the perfusate and lung
      tissue showed a significant correlation with the dose given (P<0.001) but no
      correlation with the very low plasma levels in all groups (P=0.825). ILP resulted
      in a slight deterioration of most functional parameters compared to the Sham
      group. Although there were no differences between the perfusion groups regarding
      hemodynamic and ventilatory parameters, gas exchange parameters (pO(2)/FiO(2)
      index, pCO(2), AADO(2)) demonstrated a trend toward dose-related functional
      impairment. Histological evaluation confirmed a dose-depending damage of lung
      tissue (P<0.001, correlation coefficient 0.670). The hyperthermic ILP with high
      dose cisplatin led to improved gas exchange parameters and a reduction of
      morphological lung damage. CONCLUSIONS: In vivo ILP with high-dose cisplatin
      represents a safe procedure in this pig model. Hyperthermic perfusion up to 41.5
      degrees C was beneficial to reduce the acute lung injury. The promising results
      of this study might be used for initiation of clinical trials as an alternative
      treatment in patients with a very poor prognosis.

PMID- 15450577
TI  - Intrathoracic neurogenic tumors--50 years' experience in a Japanese institution.
AB  - OBJECTIVE: Intrathoracic neurogenic tumors are relatively uncommon, and there
      have been few reports regarding their entire clinical characteristics in the
      Asian population. OBJECTIVES: We retrospectively reviewed our Japanese
      institutional experience of intrathoracic neurogenic tumors, with emphasis on the
      clinical spectrum. METHODS: We analyzed the records of 146 patients with
      intrathoracic neurogenic tumors who were treated over the past 50 years. There
      were 60 pediatric and 86 adult patients (74 males and 72 females). RESULTS: There
      were 51 ganglioneuromas, 37 schwannomas, 30 neurofibromas, 18 neuroblstomas, 5
      gangliobastomas, and 5 others, of which 136 cases were located in the posterior
      mediastinum, 9 in the chest wall, and 1 in the lung parenchyma. Neurogenic tumors
      were most commonly seen as a pediatric mediastinal tumor (46.2%), as compared to
      11.2% in the adult population (P<0.001). Eighty-four percent of adult patients
      and 60% of pediatric patients were asymptomatic. In thirteen patients (8.9%), the
      tumor showed an intraspinal extension, the so-called dumbbell-type. Overall,
      20.5% of the neoplasms were malignant, occurring predominantly in the first 5
      years of life. Complete resection was performed in 95.7% cases for benign tumors
      and 63.3% for malignant tumors, including a laminectomy for six cases of the
      dumbbell-type. There were no operative deaths and minimal morbidity. CONCLUSIONS:
      Age seemed to be the most important clinical parameter for distinguishing between
      histological type and rate of malignancy for neurogenic tumors. Recognition of
      this clinical spectrum will lead to the immediate and appropriate surgical
      intervention.

PMID- 15450578
TI  - Surgical treatment of neuroendocrine tumors of the lung.
AB  - OBJECTIVE: This report reviews the pattern of neuroendocrine (NE)
      differentiation, lymph-node involvement, extension of surgery, and survival in
      125 NE lung tumor patients. METHODS: Standard diagnostic workup included CT scan,
      bronchoscopy, bronchial biopsy or Fine Needle Aspiration Biopsy, (111)In
      pentetreotide scan (OctreoScan) and mediastinoscopy in selected patients. NE
      differentiation was assessed based on the morphology and immunohistochemical
      reactivity for pan-neuroendocrine markers NSE, CGA, and Synaptophysin. For small
      cell carcinoma (SCC), only clinical stage I and II patients underwent surgery.
      Several different surgical procedures were utilized, from limited resections to
      lobectomy, pneumonectomy, and bronchoplastic procedures. Survival was assessed
      using Kaplan-Meyer method at 5 years. RESULTS: There were 79 typical carcinoid
      (TC), eight atypical carcinoid (AC), 18 large cell carcinoma (LCC) and 20 SCC
      patients. Mean age at diagnosis was 54.6+/-15.2 (ranges from 16 to 77 years) for
      TC, 68.5+/-9.1 (range 53-81) for AC, 68.7+/-4.6 (range 58-77) for LCC, 64.6+/-7.9
      (range 48-82) for SCC. Male/female ratio was 1/1 for TC and AC, 2.6/1 for LCC and
      9/1 for SCC. Lymph-node involvement was present in 14% of TC, 0% of AC, 31.5% of
      LCC, and 45% of SCC. Cancer specific survival was 96% for TC, 87.5% for AC, 37.5%
      for LCC, and 30% for SCC at 5 years from surgery. Presenting symptoms were
      invariably of respiratory-related. None had the carcinoid syndrome. History of
      tobacco abuse ranged from 46% for TC to 100% in SCC. Survival ranged from a
      minimum of 1 month for SCC to a maximum of 168 months with no evidence of disease
      for TC. Synchronous multicentric forms were found in 14% of TC. Twenty-one
      percent (4/19) of the patients with SCC treated by induction therapy and surgery,
      and in few cases by surgery and adjuvant chemotherapy are alive without the
      evidence of the disease for 5 years. CONCLUSIONS: Due to the high percentage of
      lymph-node involvement and multicentric forms found in our series lobectomy with
      radical lymph-node dissection appears, in our opinion, the most appropriate
      surgical treatment in well-differentiated forms, while more limited resection
      appears sub-optimal. Also, due to the finding of recurrences many years after
      surgery, the follow-up must be accurate and protracted in this subgroup. Only
      Small Cell Lung Carcinoma patients in clinical stage I and II underwent surgery
      with good long-term results.

PMID- 15450579
TI  - Operative and non-operative treatment of benign subglottic laryngotracheal
      stenosis.
AB  - OBJECTIVE: Surgery is the first line of treatment for laryngotracheal stenosis;
      Montgomery tube or permanent tracheostomy have been so far the only alternatives.
      Nd-YAG laser resection and indwelling endotracheal stents have rarely been used
      in subglottic stenosis for anatomic and technical reasons. We have used the
      latter approach to optimize the timing of surgery or to achieve palliation
      without tracheostomy. METHODS: Between 1991 and 2001 we have treated 18 patients
      with subglottic stenosis (10 males, 8 females; age range 14-78, mean 34). The
      upper margin of the stricture was 2mm to 1cm below the vocal cords; the stenotic
      segment extended from 1.5 to 5 cm. Three patients had tracheostomy done
      elsewhere. Four patients (Group I) had laser and stenting by a Dumon prosthesis
      as the only treatment; six had laser and stenting (#4) followed after 1-6 months
      by laryngotracheal resection (Group II); eight had surgery alone (Group III).
      RESULTS: In Group I, one patient required repositioning of the stent and in two
      the stent was removed; two patients died of their underlying disease; at a follow
      up of 2-9 years all living patients did well but required permanent aerosolized
      therapy and periodical bronchoscopy. In Group II, we had two wound infections due
      to airway colonization by staphylococcus aureus. In Group III, two patients
      developed anastomotic postoperative stenosis, treated by laser (#2) and stenting
      (#1), and one patient with previous tracheostomy had a wound infection. Overall,
      in the 14 surgical patients (Groups II and III) stenosis occurred in 14.2% and
      infection in 21.3%. After a follow up of 15 months to 12 years, all surgical
      patients breathe and speak well. CONCLUSIONS: Laser resection and endoluminal
      stenting can be a viable alternative to surgery or optimize the timing of
      operation in patients with subglottic stenosis.

PMID- 15450580
TI  - Giant posterior mediastinal benign cystic teratomatous ganglioneurofibro-lipoma
      in the first decade.

PMID- 15450581
TI  - Cervical and mediastinal hematoma from ruptured aneurysm of the inferior thyroid
      artery.

PMID- 15450582
TI  - Aneurysmal bone cyst of the first rib.

PMID- 15450583
TI  - Aortic paraannular abscess with pseudoaneurysm of noncoronary sinus of Valsalva.

PMID- 15450584
TI  - A rare case of intimal rupture of the ascending aortic wall.

PMID- 15450585
TI  - Imminent dislodgement of atheromatous aortic plaque during insertion of a balloon
      catheter prevented by transoesophageal echocardiography.

PMID- 15450586
TI  - Cannulation of the brachiocephalic trunk during surgery of the thoracic aorta: a
      simplified technique for antegrade cerebral perfusion.
AB  - Here we present our simplified technique of cannulation of the brachiocephalic
      trunk for cardiopulmonary bypass and antegrade cerebral perfusion institution.

PMID- 15450587
TI  - Aortic valve replacement with continuously perfused beating heart in patients
      with patent bypass conduits.
AB  - We present a technique for replacement of the aortic valve in selected patients
      undergoing redo surgery in the presence of patent coronary artery bypass grafts
      and occluded native coronary arteries that affords optimal myocardial protection,
      limited dissection of the heart and minimal risk of injury to existing grafts, in
      particular, the internal mammary artery.

PMID- 15450588
TI  - Mitral valve replacement after application of atrial appendix flap in
      endocarditis with posterior annular abscess.
AB  - In patients with acute bacterial endocarditis and annular abscess formation,
      cardiac valve replacement is associated with high perioperative mortality and
      morbidity. We present two patients who had had infective endocarditis and annular
      abscess formation in the mural leaflet region. Before replacing the mitral valve,
      we covered the atrium and annulus with a flap of evaginated left atrial appendix.

PMID- 15450589
TI  - Arterial graft extension with radial artery: a method of total arterial
      revascularization.
AB  - A method of total arterial revascularization is presented. This technique is
      based on the extension of a semi-skeletonized right internal thoracic artery
      graft with an entire radial artery in an end to end fashion. A complete arterial
      revascularization is achieved with a bilateral in situ internal thoracic artery
      strategy preserving the left internal thoracic artery to the left anterior
      descending artery bypass as an isolated graft. In our experience, this pattern of
      revascularization has been especially important in patients with atheromatous
      disease of the ascending aorta, a difficult situation in which a 'no-touch
      technique' is mandatory.

PMID- 15450590
TI  - Mediastinoscopic ultrasonography (MUS).
AB  - Correct pre-therapeutic T4 staging is mandatory for neo-adjuvant studies and for
      the decision on surgical therapy of high-risk patients. T4-staging of centrally
      located lung-cancer by means of non-invasive imaging techniques is either of low
      accuracy (CT and NMR) or important regions are not accessible due to air
      interference with the tracheo-bronchial tree (trans-esophageal-endosonography,
      TEE). We here describe for the first time the new technique of mediastinoscopic
      ultrasonography (MUS). A fingertip ultrasound probe is introduced through the
      video-mediastinoscope. The probe lies in front of the tracheo-bronchial tree and
      in direct contact with the vena cava and pulmonary artery. This position allows
      examining those regions that are not accessible with TEE. In a pilot study with
      12 patients, visualization of central vessels and their relation to the tumor was
      excellent and without artifacts. In 3 patients, MUS did not confirm the T4 stage
      predicted by CT Scan. Those three patients underwent successful pneumonectomy (R0
      resection) while the other nine patients received induction treatment. MUS is a
      promising addition to CT scanning, NMR, and transesophageal ultrasound in staging
      of centrally located tumors.

PMID- 15450591
TI  - Totally endoscopic off-pump bilateral internal thoracic artery bypass grafting.
AB  - The introduction of robotic assistance has enabled totally endoscopic closed
      chest procedures, most often by left internal thoracic artery to left (LITA)
      anterior descending. Endoscopic stabilizers have made off-pump surgery feasible.
      We report the first case of a totally endoscopic off-pump bilateral ITA grafting
      in a 58-year-old patient.

PMID- 15450592
TI  - Tricuspid valve repair in a case with congenital absence of left thoracic
      pericardium.
AB  - We present a case of severe tricuspid valve insufficiency because of disruption
      of the anterior tricuspid leaflet with congenital absence of left thoracic
      pericardium. Findings suggest that tricuspid valve disruption was a result of
      distorted right ventricular geometry because of luxation of the heart into left
      thoracic cavity. Tricuspid valve could be repaired by reinsertion of anterior
      tricuspid leaflet and De-Vega annuloplasty. Normal hemodynamic was obtained and
      weaning from cardio pulmonary bypass was possible by lifting the heart in
      orthotopic position using increased positive end expiratory pressure.
      Postoperative course was uneventful.

PMID- 15450593
TI  - Dissecting sub-epicardial hematoma--challenges to surgical management.
AB  - A 67-year-old man developed a large dissecting sub-epicardial hematoma of his
      heart following a percutaneous coronary interventional procedure. While
      undergoing a dilatation of in-stent restenosis of a saphenous vein graft to the
      diagonal artery, he developed an anastomotic perforation that lead to a large sub
      epicardial hematoma that sheared of all the epicardial vessels from the
      underlying myocardium. Emergent surgery was performed as he began to evolve a
      large myocardial infarction. Evacuation of the hematoma and gluing back of the
      epicardium was the only operation possible due to the complexity of the problem.
      Deteriorating hemodynamics post-operatively led to the placement of a
      percutaneous ventricular assist device despite which he succumbed. This case
      report is intended to alert the surgical community to such a rare complication of
      aggressive percutaneous intervention, difficulty in establishing an accurate
      diagnosis and repairing the sub-epicardial dissecting hematoma.

PMID- 15450594
TI  - Unusual complication of arterial switch operation: ventricular septal aneurysm
      treated with surgical ventricular restoration.
AB  - Despite current low overall perioperative mortality, ischemic complications due
      to coronary artery translocation remain the most unwanted early complication of
      the arterial switch operation. We describe the case of a boy who underwent, at
      five days of age, one-stage arterial switch operation for transposition of the
      great arteries with repair of ventricular septal defect and coarctation of the
      aorta. Early postoperative course was complicated by severe ischemic left
      ventricle (LV) dysfunction and development of a ventricular septal aneurysm. At
      four years of age he underwent successful surgical ventricular restoration
      associated with implantation of a biventricular pacing, with complete resolution
      of heart failure symptoms.

PMID- 15450595
TI  - Endoluminal and surgical treatment for the management of Stanford Type A aortic
      dissection.
AB  - Stanford Type A aortic dissection is a life-threatening disease. A 46-year-old
      female patient with Stanford Type A aortic dissection was successfully treated by
      placing a stent-graft into the ascending aorta via femoral artery. No
      complication was found immediately after the operation. Bentall operation was
      performed to treat the development of severe aortic insufficiency 21 months after
      the stent-grafting procedure. Literature review was done to discuss the
      possibility of using endoluminal stent placement to treat Stanford Type A aortic
      dissection.

PMID- 15450596
TI  - Acute coronary syndrome following repair of aortic dissection.
AB  - Cardiac complications associated with type A aortic dissections are relatively
      common before and during the surgical repair. A cardiac event occurring a few
      days after routine recovery is rare though. We describe a case of acute occlusion
      of the left anterior descending artery by thrombus, 4 days after surgical repair,
      salvaged by emergency angioplasty and stenting. A possible explanation for the
      thrombus includes embolisation of a fragment of glue.

PMID- 15450597
TI  - Aortic root replacement after recent intracerebral hemorrhage.
AB  - A 12-year-old boy presented with an intracerebral haemorrhage secondary to
      Staphylococcus aureus endocarditis. He developed worsening aortic regurgitation
      and required aortic root replacement. In view of his recent haemorrhage, a
      heparin-bonded cardiopulmonary bypass circuit with low dose systemic
      heparinisation was used. No further intracerebral bleeding ensued and his
      neurological condition slowly improved.

PMID- 15450598
TI  - Bilateral coronary ostial patch angioplasty with autologous pericardium in
      Takayasu arteritis: a case requiring replacement of the aortic valve and
      ascending aorta.
AB  - Since the lesions and stages of Takayasu arteritis vary with each patient,
      surgical treatment of this disease requires meticulous planning for the timing of
      operation, technique, material used, and postoperative medication. We report a
      rare complex lesion of Takayasu arteritis, which required simultaneous repairs
      for aortic regurgitation, a dilated ascending aorta and bilateral coronary ostial
      stenosis. Such multiple lesions have not been reported previously. A 47-year-old
      woman was referred to us because of heart failure and chest pain. The coronary
      ostial stenosis were enlarged with generously sized autologous pericardial
      patches, and separate aortic valve and ascending aortic replacements were
      performed since the diameter of the Valsalva sinus was 37 mm. The postoperative
      course was uneventful, but steroid therapy was commenced postoperatively because
      inflammatory reaction remained high.

PMID- 15450599
TI  - Clopidogrel in coronary artery surgery.

PMID- 15450600
TI  - Delayed rupture of a primary esophageal repair for Boerhaave's syndrome.

PMID- 15450602
TI  - Dual control of membrane targeting by PtdIns(4)P and ARF.
AB  - In mammalian cells, three types of phosphatidylinositol 4-kinase (PI4K) are
      associated with the Golgi complex, where their product, phosphatidylinositol 4
      phosphate [PtdIns(4)P], is concentrated. The role of PtdIns(4)P in this
      compartment and how the PtdIns(4)P-positive membrane domain is formed and
      maintained despite continuous membrane flow are, however, poorly understood.
      Recent work has shown that PtdIns(4)P and the small GTPase ARF1 function
      cooperatively in the recruitment of four-phosphate adaptor proteins (FAPPs) to
      the trans-Golgi network (TGN) and has implicated FAPPs in formation of the
      membrane domain and in post-Golgi trafficking.

PMID- 15450603
TI  - Disulfide relays between and within proteins: the Ero1p structure.
AB  - The essential flavoenzyme Ero1p both creates de novo disulfide bonds and
      transfers these disulfides to the folding catalyst protein disulfide isomerase
      (PDI). The recently solved crystal structure of Ero1p, in combination with
      previous biochemical, genetic and structural data, provides insight into the
      mechanism by which Ero1p accomplishes these tasks. A comparison of Ero1p with the
      smaller flavoenzyme Erv2p highlights important structural elements that are
      shared by these flavin adenine dinucleotide (FAD)-binding sulfhydryl oxidases and
      suggests some general themes that might be common to proteins that generate
      disulfide bonds.

PMID- 15450604
TI  - Aminoacylation of the anticodon stem by a tRNA-synthetase paralog: relic of an
      ancient code?
AB  - The activation and charging of amino acids onto the acceptor stems of their
      cognate tRNAs are the housekeeping functions of aminoacyl-tRNA synthetases. The
      availability of whole genome sequences has revealed the existence of synthetase
      like proteins that have other functions linked to different aspects of cell
      metabolism and physiology. In eubacteria, a paralog of glutamyl-tRNA synthetase,
      which lacks the tRNA-binding domain, was found to aminoacylate tRNA(Asp) not on
      the 3'-hydroxyl group of the acceptor stem but on a cyclopentene diol of the
      modified nucleoside queuosine present at the wobble position of anticodon loop.
      This modified nucleoside might be a relic of an ancient code.

PMID- 15450605
TI  - Raptor protein contains a caspase-like domain.
AB  - Using state-of-the-art sequence analysis and structure-prediction methods a
      caspase-like domain in the N-terminal region of raptor proteins has been
      identified. This domain, which is characterized by the presence of invariant
      catalytic Cys-His dyad, is evolutionarily and structurally related to known
      caspases and might have protease activity. This finding suggests several
      unexpected aspects of raptor function in the target of rapamycin (TOR) signaling
      pathway.

PMID- 15450606
TI  - ECEPE proteins: a novel family of eukaryotic cysteine proteinases.
AB  - Using a variety of fold-recognition methods, a novel eukaryotic cysteine
      proteinase (ECEPE) family has been identified. This family encompasses sequences
      from an uncharacterized KOG4621, including the Arabidopsis thaliana guanylyl
      cyclase-related protein AtGC1. ECEPE proteins are predicted to possess the papain
      like cysteine proteinase fold and are evolutionarily linked to C39 peptidases.
      The presence of the invariant Cys-His-Asp/Asn catalytic triad and the oxyanion
      hole glutamine residue characteristic of papain-like cysteine proteases indicate
      that ECEPE proteins might function as proteases.

PMID- 15450607
TI  - Protein folding in the cell: reshaping the folding funnel.
AB  - Models of protein folding have historically focused on a subset of 'well-behaved'
      proteins that can be successfully refolded from denaturants in vitro. Energy
      landscapes, including folding funnel 'cartoons', describe the largely
      uncomplicated folding of these isolated chains at infinite dilution. However, the
      frequent failure of many polypeptides to fold to their native state requires more
      comprehensive models of folding to accommodate the crucial role of interactions
      between partially folded intermediates. By incorporating additional deep minima,
      which reflect off-pathway interchain interactions, the folding funnel concept can
      be extended to describe the behavior of a more diverse set of proteins under more
      physiologically relevant conditions. In particular, the effects of ribosomes
      (translation), molecular chaperones and other aspects of the cellular environment
      on early chain conformations can be included to account for the folding behavior
      of polypeptide chains in cells.

PMID- 15450608
TI  - A common folding mechanism in the cytochrome c family.
AB  - Of the globular proteins, cytochrome c (cyt c) has been used extensively as a
      model system for folding studies. Here we analyse the folding pathway of
      different cyt c proteins from prokaryotes and eukaryotes, and attempt to single
      out general correlations between structural determinants and folding mechanisms.
      Recent studies provide evidence that the folding pathway of several cyt c
      proteins involves the formation of a partially structured intermediate. Using
      state-of-the-art kinetic analysis on published data, we show that such a folding
      intermediate is an obligatory on-pathway species that might represent either a
      defined local minimum in the reaction coordinate or an unstable high-energy
      state. Available data also indicate that some essential structural features of
      the folding intermediate and transition states are highly conserved across this
      protein family. Thus, cyt c proteins share a consensus folding mechanism in spite
      of large differences in physico-chemical properties and thermodynamic stability.
      This novel outlook on the folding of cyt c can shed light on much published data
      and might offer a general scheme by which to plan new experiments.

PMID- 15450609
TI  - Conformation-dependent antibodies target diseases of protein misfolding.
AB  - Many degenerative diseases are fundamentally associated with aging and the
      accumulation of misfolded proteins as amyloid fibrils. Although such diseases are
      associated with different proteins, they share several pathological features.
      These similarities might be due to underlying commonalities in the pathway of
      aggregation and the structures of the various aggregation products. Because
      protein misfolding is thought to be central to the pathological state, it is
      essential to be able to distinguish such pathological states from native and non
      pathological states, especially in vivo or in complex mixtures. Conformation
      dependent antibodies that specifically recognize misfolded proteins are proving
      to be useful tools for examining the mechanisms of amyloid formation and for
      clarifying the roles of various misfolded states in pathogenesis. The common
      structures and mechanisms hold promise for the development of broad-spectrum
      drugs and vaccines that will be effective for the treatment of many of these
      diseases.

PMID- 15450610
TI  - MARKing tau for tangles and toxicity.
AB  - In healthy neurons, tau proteins regulate microtubule function in the axon. In
      the brains of individuals with Alzheimer's disease, tau is hyperphosphorylated
      and aggregated into intraneuronal deposits called neurofibrillary tangles (NFTs).
      Hyperphosporylation dislodges tau from the microtubule surface, potentially
      resulting in compromised axonal integrity and the accumulation of toxic tau
      peptides. Recent biochemical and animal model studies have re-evaluated tau
      phosphorylation and other aspects of neurofibrillar pathology. The results
      indicate that phosphorylation of tau's microtubule-binding domain by the protein
      kinase MARK primes tau for hyperphosphorylation by the kinases GSK-3 and Cdk5,
      which in turn triggers the aggregation of tau into filaments and tangles. Toxic
      consequences for the neuron might be exacerbated by tangle formation but are
      already evident during the early steps of the process.

PMID- 15450611
TI  - The eukaryotic plasma membrane as a nutrient-sensing device.
AB  - In eukaryotic cells, G-protein-coupled receptors (GPCRs), non-transporting
      nutrient carrier homologues and active nutrient carriers have been recently shown
      to function as sensors that directly monitor the level of nutrients in the
      extracellular environment. The plasma membrane is not only the cellular boundary
      at which signalling molecules that govern metabolism and proliferation are
      detected, but also the boundary across which nutrients that sustain the
      generation of energy and building blocks are transported. Nutrient sensors
      combine these functions in various ways. Classical receptor proteins detect the
      presence of nutrients, carriers combine the functions of nutrient transporters
      and receptors, and carrier homologues have lost their transport capacity and
      become pure receptors. The activation of signal transduction pathways by
      nutrients adds a new layer to the regulatory network that controls metabolism and
      proliferation. Nutrient sensors highlight the importance of both nutrients as
      signalling molecules and nutrient carriers as receptors for signalling pathways.

PMID- 15450612
TI  - Registered nurses, in acute hospital settings, have a positive impact on patient
      outcome--its official!

PMID- 15450613
TI  - Staff views on the extended role of health care assistants in the critical care
      unit.
AB  - In the changing climate of the NHS support workers such as health care assistants
      (HCAs) are becoming more prevalent in departments, wards and clinics throughout
      the National Health Service (NHS) including critical care and high dependency
      units (CCUs/HDUs) [Hind M, Jackson D, Andrewes C, Fulbrook P, Galvin K, Frost S.
      Health care support workers in the critical care setting. Nurs Crit Care
      2000;5(1):31-9; Hogan J, Playle J. The utilization of the health care assistant
      role in intensive care. Br J Nurs 2000;9(12):794-801; Wainwright TA. The
      perceived function of health care assistants in intensive care: nurses views'.
      Intens Crit Care Nurs 2002;18:171-80]. The CCU within an acute hospital Trust in
      the South East of England, which employs HCAs undertook an audit to assess staff
      views on extending the role of the HCAs and ascertain the perceived implications
      of extending their role within the unit. A re-audit was undertaken after the
      implementation of changes recommended from the initial survey to review the
      impact on the CCU staff. A semi-structured questionnaire was designed based on
      the findings of previous studies and the recommendations identified through the
      evidence-based literature review. A response rate of 64% was achieved for the
      initial audit. A second questionnaire was designed after the implementation of
      initiatives proposed in the initial audit and a 58% response rate was achieved.
      The results from the first audit indicated support for the extended role of HCAs,
      staff perception of the current HCA role and identified key tasks staff felt were
      appropriate for HCAs to undertake as part of an extended role. However, opinions
      regarding the types of skills the HCAs should acquire in an extended role, the
      method and content of training and the perceived benefits and limitations of
      extending the HCAs role within the unit varied. The results of the second
      questionnaire indicated the majority of staff were aware of the changes
      implemented, approved of the changes and were positive about the impact on the
      unit but, required more detailed information about, and involvement in, the
      continued implementation of the changes.

PMID- 15450614
TI  - Memories of intensive care and experiences of survivors of a critical illness: an
      interview study.
AB  - Recovery from a critical illness can be a complex and protracted process. It is
      known that for some, health-related quality of life (HRQOL) does not return to
      pre-illness levels for many months, and in some disease processes this may be
      longer. This study was undertaken as part of a larger project examining the pain
      and health status of survivors of a critical illness. The aims of the qualitative
      aspect of the study were to examine the participants' memories of intensive care
      and hospitalisation at 6 months post-discharge, and to explore the impact of the
      critical illness experience on their recovery. Purposive sampling was used to
      enable rich descriptions of the experience of recovery from those patients best
      able to articulate their experiences. Three common themes were found with our six
      participants: recollections, responses, and comfort/discomfort. Recovery from
      their critical illness continued to affect the participants and carers, some
      profoundly so. Better integration of services and continued support is required
      for survivors of a critical illness up to and beyond 6 months.

PMID- 15450615
TI  - Visits of children to patients being cared for in adult ICUs: policies,
      guidelines and recommendations.
AB  - Little is known about the frequency of children visiting their nearest relatives
      in adult ICUs or if there are any policies/guidelines or recommendations
      regarding these. The aims of this multi-centre descriptive study were to survey
      Swedish ICUs policies/guidelines or recommendations, and examine the reasons
      given both for and against restricting child visits; if parents/guardians sought
      advice in connection with such visits, and if any differences in demographic data
      could be ascertained. Fifty-six Lead Nurse Managers (LNM), representing as many
      general adult ICUs, participated by answering a questionnaire. Only one ICU had
      written policy/guidelines concerning child visits; most ICUs (70%) had no
      policies/guidelines at all. All LNMs reported that their ICU was positive to
      child visits, but only two actively encouraged these. Nineteen (34%) of the ICUs
      restricted child visits. More than 50% of the LNMs reported that only about half
      of their patients ever had visits from children. Seventy percent of the ICUs had
      no restrictions on visiting hours, but 30% imposed some form of restriction.
      Twenty LNMs reported that 75% of the parents/guardians of children 0-6 years old
      asked for advice about child visits. However, those responsible for children >12
      years of age seldom asked for any advice at all.

PMID- 15450616
TI  - Management of the changeover of inotrope infusions in children.
AB  - Inotropes are drugs that can assist the critically ill patient's heart to
      function more effectively by increasing contractility. Inotrope infusions are run
      continuously and fresh infusions are required on a regular basis. The two methods
      of changeover commonly used are the quick-change and the double-pump methods.
      Haemodynamic compromise can occur to some degree with both methods. Evidence
      regarding the most effective method is limited to individual experience and
      anecdote. Therefore, the aim of this project was to determine the best method of
      changing inotropic infusions in children. METHODS: Thirty children receiving
      inotropes post-cardiac surgery admitted to PICU were included in the study. There
      were two methods of changing over inotropes in this study: Method 1, quick-change
      and Method 2, double infusion. A rescue bolus of 0.1 ml of the changeover
      inotrope was given for drops in mean arterial pressure (MAP) > or = 20% during
      the changeover period. RESULTS: Repeated measures analysis for MAP demonstrated
      no significant difference in the mean percentage change from baseline during the
      30-min changeover period. Quick-change: -0.297 (95% CI: -6.43 to 0.5) and double
      pump: 3.73 (95% CI: -2.81 to 10.27) (P = 0.078). CONCLUSIONS: There was no
      statistically or clinically significant difference detected in changes to MAP. A
      rescue bolus was required on only one occasion during quick-change over for a
      reduction in MAP of > or = 20% in the quick-change group. Therefore, a quick
      change method can be considered more effective as it reduces the time required
      for changeover and the risk of tolerance to higher levels of inotrope, while
      maintaining haemodynamic stability in children after cardiac surgery.

PMID- 15450617
TI  - Coping strategies of relatives when an adult next-of-kin is recovering at home
      following critical illness.
AB  - The trend within the Swedish healthcare system is to reduce the duration of
      hospital care. This means that a patient who is discharged to their home after
      critical illness is highly likely to be functionally impaired, and therefore,
      requires care-giving assistance from a family member. The aim of this study was
      to generate a theoretical model with regard to relatives' coping when faced with
      the situation of having an adult next-of-kin recovering at home after critical
      illness. The design incorporated grounded theory methodology. Four coping
      strategies exhibiting different characteristics were identified: volunteering,
      accepting, modulating and sacrificing. Factors determining the choice of coping
      strategy were the physical and psychological status of the relative, previous
      experience of ICU-care and the psychological status of the patient. The
      theoretical model described in this article can contribute to expanding
      healthcare professionals' understanding of the coping strategies of relatives
      during recovery, but also provide inspiration for social action to be taken.

PMID- 15450618
TI  - Increasing awareness of tissue donation: in the non-heart beating donor.
AB  - Many healthcare professionals (nursing and medical staff) are familiar with
      asking families to consider organ donation in the brain-stem death patient. In
      contrast few healthcare professionals raise the subject of tissue donation with
      the newly bereaved non-heart beating donor (NHBD) families following cardiac
      death. The failure of healthcare professionals to approach theses families is
      strongly supported in the literature [Crit. Care Nurs. Clin. N. Am. 4 (1992) 63;
      William and Calif, 1996; Prof. Nurse 12 (1997) 482]. Coyle [Intensive Crit. Care
      Nurs. 16 (2000) 45] identified that for many nurses the conflict arises from the
      ethical principle of beneficence to do good and non-maleficence to do no harm.
      However, why is requesting organ and/or tissue donation an ethical issue, should
      it not be part and parcel of the care offered to bereaved families? Are
      healthcare professionals not making an issue of it? This article critically
      analyses the issues surrounding tissue donation and the role of healthcare
      professionals in raising awareness of eligibility for tissue donation. A tool of
      structured reflection [J. Nurse Manager 1 (1993) 9] will be used to highlight the
      use of reflective practice following a critical incident. On the basis of
      analysis of current practice consideration will be given for future theoretical
      arguments in development, research, and education.

PMID- 15450619
TI  - The experiences of partners of critically ill persons in an intensive care unit.
AB  - The aim of this study was to describe partners' experiences when their spouses
      received care in an intensive care unit (ICU). Seven partners were interviewed
      using a narrative approach. The interview texts were subjected to qualitative
      thematic content analysis. The analysis resulted in three themes; being present,
      putting oneself in second place and living in uncertainty. It was a shocking
      experience for the partners to see their critically ill spouse in the ICU. It was
      important to be able to be present; nothing else mattered. Showing respect,
      confirming the integrity and dignity of their critically ill spouse were also
      essential for partners. Receiving support from family and friends was important,
      as were understanding and accepting what had happened, obtaining information and
      the way in which this was given. The state of uncertainty concerning the outcome
      for the critically ill person was difficult to cope with. The partners wanted to
      hope, even though the prognosis was poor.

PMID- 15450620
TI  - Clinical research 2: legal and ethical issues in research.

PMID- 15450621
TI  - Economic analysis of eating and physical activity: a next step for research and
      policy change.
AB  - Poor nutrition and physical inactivity are among the leading causes of morbidity
      and mortality in the United States, and widespread behavior modification is
      needed to improve health now and in the future. There is growing evidence that
      modifications in the physical environment and in social policies will be required
      to accomplish this goal. There is also growing recognition that economic factors
      have contributed to current eating and physical activity patterns, and that
      economic factors need to be considered when developing strategies for improving
      these behaviors. Identifying where economic and public health priorities converge
      could suggest new avenues for sustainable policy changes, which will, in turn,
      promote healthy choices on both an individual and population-wide level. To
      review the effect that economics has on eating and physical activity behaviors,
      the Partnership to Promote Healthy Eating and Active Living convened an Economic
      Analysis Forum. Two working groups were formed-one focusing on eating behaviors
      and one on physical activity, and both with equal representation from health
      related and economic disciplines. The groups examined how economics has
      contributed to present eating and physical activity patterns and how economics
      could be used to develop interventions to improve these patterns. This article
      describes the challenges the groups faced in their work, the way in which the
      public health and economic approaches were integrated, and the questions left
      unanswered.

PMID- 15450622
TI  - An economic framework for understanding physical activity and eating behaviors.
AB  - This paper offers an economic framework of human behavior with respect to
      physical activity and nutrition. Economics offers useful insights into these
      behaviors because it is the study of how people allocate their scarce resources
      of time and money to maximize their lifetime happiness. This paper outlines the
      criteria for policy interventions from an economic perspective and also considers
      arguments for policy intervention that are not based on economic considerations.
      The implications of the economic framework are summarized and its limitations are
      described.

PMID- 15450623
TI  - The economics of physical activity: societal trends and rationales for
      interventions.
AB  - What are Americans doing with their time and their money and what has changed in
      recent decades? Do changes suggest interventions that will lead to healthier
      lifestyles? This paper analyzes several different data sets that reveal some
      surprising (and some less surprising) insights. The big growth areas, both in
      terms of expenditure and time allocation, have been leisure time and
      travel/transportation. Leisure-time industries outpace gross-domestic-product
      growth for both "active" (sporting goods, dance studios, gyms) and "sedentary"
      industries (spectator sports, cable TV), although industries associated with more
      sedentary lifestyles grow the fastest. Overall time spent in productive
      activities, whether at home or work, has declined by several hours each week for
      both men and women compared to 40 years ago. Reduced physical activity by itself
      is not a reason for intervening, as many changes improved overall quality of life
      (even if not necessarily health-related quality of life). But other trends are
      more likely to reflect poorly functioning markets, leading to worse economic and
      health outcomes. Market failures that lead to less physical activity or unhealthy
      nutrition justify interventions, both from an economic and a public health
      perspective.

PMID- 15450624
TI  - Economic interventions to promote physical activity: application of the SLOTH
      model.
AB  - Physical inactivity is responsible for major health and economic costs in the
      United States. Despite widespread recognition of the scope and importance of the
      problem of physical inactivity, only modest progress has been made in improving
      overall physical activity in the U.S. population. This paper applies a combined
      economic and public health perspective to better understand physical activity
      behavior and to guide a search for promising new economically oriented
      interventions to increase physical activity at the population level. This
      perspective is operationalized as the SLOTH model-a time-budget model
      incorporating Sleep, Leisure, Occupation, Transportation, and Home-based
      activities. Key economic forces that may influence individuals' choices about
      utilization of time and physical activity are identified. Potential interventions
      are proposed in response to each of the important forces and are evaluated on
      four criteria: (1) economic efficiency, (2) equity, (3) effectiveness, and (4)
      feasibility. The SLOTH model provides guidance regarding interventions that might
      increase physical activity in each of the four nonsleep domains. Economic
      intervention strategies are proposed and compared to economic and public health
      criteria. The results provide a starting point for selecting and evaluating
      potentially effective and feasible economic interventions that might be
      implemented as part of a larger effort to address the health crisis of inactive
      lifestyles and obesity.

PMID- 15450625
TI  - Economic determinants of urban form: resulting trade-offs between active and
      sedentary forms of travel.
AB  - Economic factors have an impact on how the built environment is shaped, which in
      turn affects how we choose to travel. Regional transportation investment
      decisions are firmly rooted in economic "cost-benefit" trade-off considerations.
      The placement (central or outlying) and mode of transportation in which
      investments are made (transit, highway, sidewalks, or bikeways) influence where
      homes, businesses, schools, and other types of uses are located. Transportation
      investments create or limit access and establish a set of economic trade-offs
      that help determine if an area will be compact or dispersed, and mixed use or
      single use. Developers consider cost trade-offs between constructing connected
      street grids versus disconnected cul-de-sac networks, which determines if
      residents can walk to services and transit. Taken collectively, transportation
      investments and resulting land-use patterns determine if destinations are far
      apart or close together and linked with direct and safe sidewalks or bikeways.
      The end result is a built environment that determines whether walking and biking
      is feasible or perceived as more beneficial than driving or taking transit. This
      paper assesses (1) the economic forces that shape transportation investment
      decisions, (2) the economic impact of these investments on land use, and (3) how
      we as consumers choose to travel as a result of these transportation investment
      and land-use decisions.

PMID- 15450626
TI  - Obesity and the food environment: dietary energy density and diet costs.
AB  - The highest rates of obesity in the United States occur among population groups
      with the highest poverty rates and the least education. The impact of
      socioeconomic variables on obesity may be mediated, in part, by the low cost of
      energy-dense foods. The observed inverse relationship between energy density of
      foods, defined as available energy per unit weight (kilocalories per gram or
      megajoules per kilogram), and energy cost (dollars per kilocalorie or dollars per
      megajoule) means that diets based on refined grains, added sugars, and added fats
      are more affordable than the recommended diets based on lean meats, fish, fresh
      vegetables, and fruit. Taste and convenience of added sugars and added fats can
      also skew food choices in the direction of prepared and prepackaged foods.
      Paradoxically, attempting to reduce diet costs may lead to the selection of
      energy-dense foods, increased energy intakes, and overweight. The present energy
      cost framework provides an economic explanation for the observed links between
      obesity and the food environment, with diet cost as the principal intervening
      variable. If higher food costs represent both a real and perceived barrier to
      dietary change, especially for lower-income families, then the ability to adopt
      healthier diets may have less to do with psychosocial factors, self-efficacy, or
      readiness to change than with household economic resources and the food
      environment. Continuing to recommend costly diets to low-income families as a
      public health measure can only generate frustration and culpability among the
      poor and less-well educated. Obesity in America is, to a large extent, an
      economic issue.

PMID- 15450627
TI  - Pros and cons of proposed interventions to promote healthy eating.
AB  - The increased prevalence and costs associated with the obesity epidemic have made
      preventive efforts a public health priority. Public health has historically
      relied on a series of targeted regulations, taxes, and education efforts to curb
      epidemics, and will rely on similar strategies to combat obesity. We argue that
      interventions targeted at youth are relatively easy to justify on economic
      grounds due to the additional protections that this group requires, but that
      justification for government interventions aimed at curbing obesity among adults
      requires additional evidence that private markets are not functioning properly.
      We then present seven proposed intervention strategies to promote healthy eating,
      and use an economic framework to discuss the relative merits of the
      interventions. This evaluation will allow policymakers to make more informed
      decisions concerning the relative merits of these strategies in combating the
      obesity epidemic.

PMID- 15450628
TI  - An economic analysis of eating and physical activity behaviors: exploring
      effective strategies to combat obesity.

PMID- 15450629
TI  - Integrating economic thinking into research on the dynamics of obesity:
      challenges and opportunities.

PMID- 15450630
TI  - Reducing drinking and related harms in college: evaluation of the "A Matter of
      Degree" program.
AB  - OBJECTIVES: To examine the effects of a multisite environmental prevention
      initiative, the "A Matter of Degree" (AMOD) program, on student heavy alcohol
      consumption and resultant harms at ten colleges. METHODS: A quasi-experimental
      longitudinal analysis of alcohol consumption and harms was employed, using
      repeated cross-sectional survey data from the Harvard School of Public Health
      College Alcohol Study (CAS). Areas examined included seven measures of alcohol
      consumption, thirteen measures of alcohol-related harms, and eight measures of
      secondhand effects of alcohol use by others. Comparisons were conducted on self
      reported behavior of students for the ten AMOD sites in aggregate and by level of
      program implementation, with students at 32 comparison colleges in the CAS, for
      each outcome. RESULTS: No statistically significant change was found in the
      overall ten-school AMOD program for outcome measures of interest from baseline
      (1997) to follow-up (2001). However, there was variation in the degree of
      environmental program development within AMOD during the intervention period. A
      pattern of statistically significant decreases in alcohol consumption, alcohol
      related harms, and secondhand effects was observed, reflecting minor to more
      substantial changes across measures among students at the five program colleges
      that most closely implemented the AMOD model of environmental change. No similar
      pattern was observed for the low implementation sites or at 32 comparison
      colleges. CONCLUSIONS: While there was no change in the ten AMOD schools in study
      measures, significant although small improvements in alcohol consumption and
      related harms at colleges were observed among students at the five AMOD sites
      that most closely implemented the environmental model. Fidelity to a program
      model conceptualized around changing alcohol-related policies, marketing, and
      promotions may reduce college student alcohol consumption and related harms.
      Further research is needed over the full course of the AMOD program to identify
      critical intervention components and elucidate pathways by which effects are
      realized.

PMID- 15450631
TI  - Prevalence of adult binge drinking: a comparison of two national surveys.
AB  - BACKGROUND: Binge drinking (defined as five or more drinks on an occasion) causes
      approximately half of the estimated 85,000 alcohol-related deaths in the United
      States each year. The Behavioral Risk Factor Surveillance System (BRFSS), a
      telephone survey, and the National Survey on Drug Use and Health (NSDUH), an in
      person survey, provide population-based estimates of binge drinking. Evaluating
      the concordance of binge drinking estimates from the BRFSS and the NSDUH is
      important for surveillance and for planning prevention programs. METHODS: In
      2003, combined data on binge drinking for 1999 and 2001 from the BRFSS (n
      =355,371) and the NSDUH (n =87,145) were analyzed for respondents aged >or=18
      years. RESULTS: National binge drinking estimates were 14.7% (95% confidence
      interval [CI]=14.5-15.2) for BRFSS and 21.6% (CI=21.2-22.0) for NSDUH. Although
      there was good correlation between state-specific binge drinking estimates from
      the two surveys (Pearson's r =0.82), the BRFSS state estimates were significantly
      lower (p <0.05) than the NSDUH estimates in 46 states and the District of
      Columbia. The demographic characteristics of binge drinkers and the wording of
      the binge question were similar in the two surveys. However, in 1999, NSDUH
      changed from paper interviews to computer-administered interviews, and
      incorporated an internal validity check with feedback questions to resolve
      inconsistent responses. CONCLUSIONS: Estimates of binge drinking from the NSDUH
      were consistently higher than those from the BRFSS, probably due to differences
      in survey methodology. Continued efforts to improve binge drinking surveillance
      are important for preventing this public health problem.

PMID- 15450632
TI  - Changes in beverage intake between 1977 and 2001.
AB  - OBJECTIVE: To examine American beverage consumption trends and causes. METHODS:
      Nationally representative data from the 1977-1978 Nationwide Food Consumption
      Survey, the 1989-1991 and 1994-1996 (also for children aged 2 to 9 years in 1998)
      Continuing Surveys of Food Intake by Individuals (CSFII), and 1999-2001 National
      Health and Nutrition Examination Survey were used in this study. The sample
      consisted of 73,345 individuals, aged >or=2 years. For each survey year, the
      percentage of total energy intake from meals and snacks was calculated separately
      for respondents aged 2 to 18 years, 19 to 39, 40 to 59, and >or=60. The
      percentage of energy intake by location (at home consumption or preparation,
      vending, store eaten out, restaurant/fast food, and school), as well as for
      specific beverages was computed separately for all age groups. The proportion
      consumed, mean portion size, and number of servings were calculated. RESULTS: For
      all age groups, sweetened beverage consumption increased and milk consumption
      decreased. Overall, energy intake from sweetened beverages increased 135% and was
      reduced by 38% from milk, with a 278 total calorie increase. These trends were
      associated with increased proportions of Americans consuming larger portions,
      more servings per day of sweetened beverage, and reductions in these same
      measures for milk. CONCLUSIONS: There is little research that has focused on the
      beneficial impacts of reduced soft drink and fruit drink intake. This would seem
      to be one of the simpler ways to reduce obesity in the United States.

PMID- 15450633
TI  - Fast food, race/ethnicity, and income: a geographic analysis.
AB  - BACKGROUND: Environmental factors may contribute to the increasing prevalence of
      obesity, especially in black and low-income populations. In this paper, the
      geographic distribution of fast food restaurants is examined relative to
      neighborhood sociodemographics. METHODS: Using geographic information system
      software, all fast-food restaurants within the city limits of New Orleans,
      Louisiana, in 2001 were mapped. Buffers around census tracts were generated to
      simulate 1-mile and 0.5-mile "shopping areas" around and including each tract,
      and fast food restaurant density (number of restaurants per square mile) was
      calculated for each area. Using multiple regression, the geographic association
      between fast food restaurant density and black and low-income neighborhoods was
      assessed, while controlling for environmental confounders that might also
      influence the placement of restaurants (commercial activity, presence of major
      highways, and median home values). RESULTS: In 156 census tracts, a total of 155
      fast food restaurants were identified. In the regression analysis that included
      the environmental confounders, fast-food restaurant density in shopping areas
      with 1-mile buffers was independently correlated with median household income and
      percent of black residents in the census tract. Similar results were found for
      shopping areas with 0.5-mile buffers. Predominantly black neighborhoods have 2.4
      fast-food restaurants per square mile compared to 1.5 restaurants in
      predominantly white neighborhoods. CONCLUSIONS: The link between fast food
      restaurants and black and low-income neighborhoods may contribute to the
      understanding of environmental causes of the obesity epidemic in these
      populations.

PMID- 15450634
TI  - Barriers to physical activity: qualitative data on caregiver-daughter perceptions
      and practices.
AB  - BACKGROUND: There is little research on household and physical environment
      barriers to physical activity, particularly in minority populations at high risk
      for obesity and inactivity. Few studies include data on caregiver and daughter
      dyads. Formative data were used to develop intervention strategies and pathways
      for the Girls Rule! obesity prevention intervention, in under-studied high-risk
      pre-adolescents. METHODS: Participants included 12 African-American girls (mean
      age 7.8 years) and their 11 primary female caregivers (mean age 41.8 years)-
      eight mother-daughter dyads and three grandmother-granddaughter dyads--for a
      total of 51 interviews across 23 participants interviewed from April to October
      2000.A qualitative approach was used for 51 semistructured in-depth interviews
      with 11 dyads (female caregiver and girl), consisting of up to three interviews
      per respondent (mean=2.4 interviews per respondent). Interviews were transcribed,
      coded, and systematically analyzed between January 2002 and January 2003 to
      identify recurrent patterns and themes related to physical activity. RESULTS:
      Findings indicate clear preference of the girls for sedentary, rather than
      active, behaviors. Caregivers were unaware of the amount of TV viewed and found
      positive benefits of TV viewing, including safe supervision of their daughters.
      Barriers to physical activity include perceived lack of affordable and accessible
      recreation facilities and low caregiver motivation. Potential intervention
      strategies identified by respondents include walking for exercise and
      transportation and several low-cost, favored physical activities, such as
      hopscotch, jumping rope, and dance. CONCLUSIONS: These findings point toward
      several physical activity and obesity intervention strategies that can guide
      obesity prevention efforts.

PMID- 15450635
TI  - Adolescent depression and suicide risk: association with sex and drug behavior.
AB  - BACKGROUND: Depression is common among adolescents, and suicide is the third
      leading cause of death among 15- to 19-year-olds. Although both health problems
      have been associated with drug use and early sexual intercourse, the relationship
      has not been systematically studied in a nationally representative sample.
      METHODS: Sixteen patterns of combined sex and drug use behaviors were obtained
      using cluster analysis of responses to Wave I of the National Longitudinal Study
      of Adolescent Health conducted from September 1994 through December 1995.
      Bivariate and multivariate analyses tested correlations between behavior patterns
      and current depression, serious suicidal ideation, and previous suicide attempt,
      controlling for gender, race/ethnicity, Hispanic ethnicity, family structure, and
      parent education. RESULTS: Compared to youth who abstain from risk behaviors,
      involvement in any drinking, smoking, and/or sexual activity was associated with
      significantly increased odds of depression, suicidal ideation, and suicide
      attempts. Odds ratios were highest among youth who engaged in illegal drug use.
      There were few differences between boys and girls who abstain from sex and drug
      behaviors. Girls were less likely than boys to engage in high-risk behaviors, but
      those who did tended to be more vulnerable to depression, suicidal ideation, and
      suicide attempt. CONCLUSIONS: Teens engaging in risk behaviors are at increased
      odds for depression, suicidal ideation, and suicide attempts. Although causal
      direction has not been established, involvement in any sex or drug use is cause
      for concern, and should be a clinical indication for mental health screening for
      girls; both boys and girls should be screened if engaging in any marijuana or
      illegal drug use.

PMID- 15450636
TI  - Prenatal and postpartum smoking abstinence a partner-assisted approach.
AB  - BACKGROUND: A partner's provision of support and smoking status has been
      consistently associated with women's likelihood of smoking cessation during
      pregnancy and relapse in postpartum. DESIGN: A three-group randomized controlled
      intervention trial was conducted in 1996 to 2001, with 583 women and their
      partners randomized to usual care (UC), woman-only (WO), or partner-assisted (PA)
      intervention. Follow-ups occurred at 28 weeks of pregnancy, and 2-, 6-, and 12
      months postpartum. SETTING: Womack Army Medical Center (WAMC) at Fort Bragg in
      Fayetteville, North Carolina. INTERVENTION: Women in the UC condition received
      provider advice to quit and a self-help guide. The WO condition received UC
      components plus a late-pregnancy relapse prevention kit (booklet and gift items)
      and six counseling calls (three in pregnancy and three postpartum) initiated by a
      health advisor. Women in the PA condition received the WO intervention, and their
      partners received telephone counseling and a support guide emphasizing skills to
      help the woman build and maintain her confidence to quit smoking. Partners who
      smoked also received cessation aids and related counseling. MAIN OUTCOME MEASURE:
      Seven-day self-reported abstinence from smoking at each follow-up. RESULTS:
      Intent-to-treat analyses showed no significant differences by condition in
      women's reports of abstinence at any follow-up. In late pregnancy, more partners
      were abstinent in the PA condition (15%) than in the UC condition (5%), p =0.02.
      CONCLUSIONS: Partner-assisted smoking-cessation interventions need further
      refinement. Influencing young couples' support patterns may require more
      intensive and conjoint intervention. Partners who smoke could benefit from
      support for their cessation efforts.

PMID- 15450637
TI  - Cancer risk assessment: quality and impact of the family history interview.
AB  - BACKGROUND: Identification of individuals at high risk for colon and breast
      cancer requires an adequate family history assessment and can influence cancer
      screening and genetic testing decisions. Little data exist that evaluate the
      completeness of the family history interview in primary care. METHODS:
      Retrospective chart review of 995 new patient visits to 28 primary care
      physicians evaluating the completeness of the family cancer history for colon or
      breast cancer. Family history information was evaluated for inclusion of age at
      diagnosis, degree of kinship, and specification of disease of interest. RESULTS:
      Family history information on cancer diagnoses was collected on 679 (68%) of the
      patients. Specific information regarding the individual affected and the cancer
      diagnosis was present in 414 (61%) of the records. Affected first-degree
      relatives were more likely to have their age of cancer diagnosis recorded than
      second-degree relatives (39%, 95% confidence interval [CI]=34%-44% vs 16%, 95%
      CI=12%-20%). Age at diagnosis of cancer in first-degree relatives was documented
      in 51% of colon cancers, 38% of breast cancers, and 27% of ovarian cancers. Only
      17% of individuals who meet criteria for early-onset breast cancer genetic
      testing were referred for genetic services. CONCLUSIONS: Adequate cancer risk
      assessment using family history information requires age at cancer diagnosis and
      specification of a cancer diagnosis. Age at diagnosis was frequently missing from
      family history assessments, which could have a potential impact on identification
      of high-risk individuals. When family history information does identify high-risk
      individuals, only the minority are referred for genetic services.

PMID- 15450638
TI  - Estimates of medical device--associated adverse events from emergency
      departments.
AB  - BACKGROUND: The true public health burden of adverse events associated with
      medical devices is unknown. The purpose of this study, therefore, was to produce
      the first-ever national estimates of medical device-associated adverse events
      resulting in emergency department (ED) visits. METHODS: From July 1999 through
      June 2000, reports of 10,395 medical device-associated adverse events were
      accumulated using the National Electronic Injury Surveillance System (NEISS),
      which collects information on product-related injuries from the ED records of a
      national stratified probability sample of hospitals. The reports were used to
      estimate annual total number of medical device-associated adverse events as well
      as number of adverse events associated with specific devices, injury diagnoses,
      demographic characteristics, and patient disposition status. RESULTS: The total
      estimated number of adverse events was 454,383 (95% confidence interval
      [CI]=371,156-537,610), involving a broad range of devices from 15 medical
      specialty groups. Unintentional traumatic events associated with a particular
      device appeared to be the most common mechanism of injury. The most prevalent
      types of injuries included contusions/abrasions, punctures, and lacerations; 13%
      of total estimated cases resulted in patient hospitalization. Adverse events
      occurred within healthcare facilities, and some were occupationally related,
      although they occurred at home more frequently than any other location (about
      42%). CONCLUSIONS: The magnitude of the total estimate, which is over four times
      greater than the annual number of adverse event reports received by medical
      device-regulating surveillance systems, emphasizes medical device-associated
      adverse events as an under-recognized public health problem. Planned collection
      of more detailed NEISS data will allow for appropriate public health
      interventions.

PMID- 15450639
TI  - Consequences of declining survey response rates for smoking prevalence estimates.
AB  - BACKGROUND: Response rates have been declining in statewide tobacco surveys. This
      study investigated whether there was associated evidence of increasing bias in
      smoking prevalence estimates. METHODS: Demographic characteristics of respondents
      to tobacco surveys in Massachusetts and California were compared to population
      data in the early 1990s, when response rates were high, and in more recent years,
      when response rates were lower. State estimates of smoking prevalence at three
      times were compared with estimates from the Current Population Survey Tobacco Use
      Supplement (CPS-TUS), conducted by the U.S. Census Bureau. RESULTS: Under- and
      over-representation of population subgroups has not changed as response rates
      have declined. Smoking prevalence estimates from state surveys remain relatively
      close to the state-specific CPS-TUS estimates. CONCLUSIONS: There is no evidence
      that declining response rates have resulted in less accurate or biased estimates
      of smoking behavior.

PMID- 15450640
TI  - Smoking status and quality of life: a longitudinal study among adults with
      disabilities.
AB  - BACKGROUND: Current research suggests that people with disabilities are more
      likely to use tobacco, less likely to quit, and less likely to be screened for
      tobacco use. However, little is known about the impact of changes in smoking
      status on the health-related quality of life (HRQL) of people with disabilities.
      OBJECTIVE: The primary objective of this paper is to examine the association
      between changes in HRQL and smoking status over time among people with
      disabilities. METHODS: The study data were derived from the Massachusetts Survey
      of Secondary Conditions, a longitudinal survey of adults with disabilities; Phase
      I was conducted in 1996-1998, Phase II in 1998-1999, and Phase III in 1999-2000.
      The main outcome measure was HRQL as measured by the Medical Outcomes Study Short
      Form-36 (SF-36). Analysis was primarily done in 2003. RESULTS: Current smokers
      and those who began smoking during follow-up had significantly poorer HRQL
      compared with nonsmokers with disabilities. Longitudinal analysis suggests that
      controlling for age, gender, race/ethnicity, education, and activities of daily
      living, changes in HRQL scores over time were associated with changes in smoking
      status. Compared to smokers, those who quit smoking during follow-up experienced
      a significant improvement in mean SF-36 scores over time for the dimensions of
      mental health, energy and vitality, and general health. CONCLUSIONS: Findings
      from this study highlight a strong need to inform public health programs, people
      with disabilities and healthcare providers about the association between tobacco
      cessation and improved health-related quality of life among people with
      disabilities.

PMID- 15450641
TI  - Advances in measurement and intervention for excessive drinking.

PMID- 15450642
TI  - Economic and environmental costs of obesity: the impact on airlines.

PMID- 15450643
TI  - A longitudinal evaluation of treatment engagement and recovery stages.
AB  - Recent methodological advancements for structural equation modeling were used to
      test a comprehensive version of the TCU Treatment Model, especially for
      addressing the hypothesized sequential relationships of early engagement
      components (participation and therapeutic relationship) and early recovery
      (psychosocial and behavioral changes) that contribute to retention and
      posttreatment recovery. Relationships among pretreatment patient motivation,
      treatment process elements, a cognitive-based treatment strategy, retention, and
      drug use outcomes were estimated using intake, during treatment, and 1-year
      followup data for 711 patients in outpatient methadone treatment. Hypothesized
      sequential elements representing treatment process and patient functioning were
      supported, and relationships between these components were estimated also as odds
      ratios as an aid for translating the findings and increasing their clinical
      usefulness to treatment settings.

PMID- 15450644
TI  - A conceptual framework for drug treatment process and outcomes.
AB  - Evidence from specialized treatment evaluations and large-scale natural studies
      of treatment effectiveness is organized conceptually into a "treatment model" for
      summarizing how drug treatment works. Sequential relationships between patient
      and treatment program attributes, early patient engagement, recovery stages,
      retention, and favorable outcomes are discussed--along with behavioral,
      cognitive, and skills training interventions that have been shown to be effective
      for enhancing specific stages of the patient recovery process. Applications of
      the treatment model for incorporating science-based innovations into clinical
      practice for improving early engagement and retention, performance measurements
      of patient progress, program monitoring and management using aggregated patient
      records, and organizational functioning and systems change also are addressed.

PMID- 15450645
TI  - Evaluation of a group-based substance abuse treatment program for adolescents.
AB  - The effectiveness of adolescent substance abuse treatment has been repeatedly
      demonstrated, but specific treatment approaches have rarely been sufficiently
      documented to permit replication. This study evaluated the effectiveness of a
      manual-guided, outpatient, group-based treatment program for adolescents (N =
      194) who were mild-to-moderate substance abusers. In addition to evaluating the
      group-based treatment model, the study was designed to compare the effectiveness
      of two approaches to preparing youth to engage in treatment, whereby adolescents
      received one of two types of treatment induction, either motivational
      interviewing or counseling overview. Self-reported pretreatment substance use and
      criminal behaviors were compared with these behaviors 6 and 12 months following
      treatment entry using a General Linear Mixed Model analytic approach that
      controlled for the effects of potential confounding variables and examined
      individual and program factors that might explain treatment response.
      Participants significantly reduced marijuana use at 6 months, and these
      reductions were largely sustained at 12 months. No changes in alcohol use or
      criminal involvement were obtained. Further examination of marijuana use
      indicated differential treatment response based on participants' emotional abuse
      history, family satisfaction, school adjustment, and pretreatment substance use
      frequency. This treatment approach appears promising for marijuana-abusing youth.

PMID- 15450646
TI  - Interpersonal maladjustment as predictor of mothers' response to a relational
      parenting intervention.
AB  - In previous work, Luthar and Suchman (2000, Development & Psychopathology, 12,
      235) reported results of a randomized clinical trial testing the efficacy of the
      Relational Psychotherapy Mothers' Group (RPMG) for methadone-maintained mothers.
      In this extension, we examined maternal interpersonal maladjustment as a
      predictor of differential response to RPMG versus standard drug counseling (DC).
      We predicted that RPMG mothers with high levels of interpersonal maladjustment
      would improve on parent-child relationship indices, whereas DC mothers with high
      levels of interpersonal maladjustment would show no improvement. Fifty-two
      mothers enrolled in the study completed baseline, post-treatment and 6-month
      followup assessments and a subset of 24 "target" children between the ages of 7
      and 16 completed measures on mothers' parenting. As predicted, results of
      hierarchical regression analyses indicated moderate interpersonal maladjustment x
      treatment interaction effects for all parenting outcomes at post-treatment and
      for a subset of outcomes at followup. Plotted interactions confirmed predictions
      that, as maternal interpersonal maladjustment increased, parenting problems
      improved for RPMG mothers and remained the same or worsened for DC mothers.
      Results indicate the potential value of interpersonally oriented interventions
      for substance-abusing mothers and their children.

PMID- 15450647
TI  - Effects of combined counseling and case management to reduce HIV risk behaviors
      among Hispanic drug injectors in Puerto Rico: a randomized controlled study.
AB  - This study examined the effectiveness of a combined counseling and case
      management behavioral intervention, using motivational interviewing strategies,
      in engaging Hispanic injection drug users in treatment and reducing drug use and
      injection-related HIV risk behaviors. Follow up data are presented on 440 (79.0%)
      of 557 randomized participants, 6 months after the initial interview. Subjects in
      the experimental arm were significantly less likely to continue drug injection
      independent of entering drug treatment, and were also more likely to enter drug
      treatment. Subjects in both arms who entered drug treatment were less likely to
      continue drug injection. Among subjects who continued drug injection, those in
      the experimental arm were significantly less likely to share needles. Confirming
      the outcomes of this study in other Hispanic sites and populations could be a
      critical step towards reducing factors that contribute to the self-sustaining
      HIV/AIDS epidemic in Puerto Rico and communities in the U.S. mainland.

PMID- 15450648
TI  - Consensus statement on office-based treatment of opioid dependence using
      buprenorphine.
AB  - Buprenorphine and buprenorphine/naloxone (BUP) are newly approved for office
      based treatment of opioid dependence. Federal and non-federal regulatory and
      monitoring agencies, national and international researchers, national
      professional organizations, researchers involved in monitoring, opioid treatment
      programs and the pharmaceutical industry met to synthesize and disseminate
      practical information to guide training, practice, monitoring, regulation and
      evaluation efforts with these medications. We performed a review of the
      literature, training curricula and practice guidelines and commissioned
      manuscripts describing recently completed, or still in progress, studies or field
      experiences with BUP treatment. A consensus process generated fifteen statements:
      (1) The federal government should collect baseline data on opioid-related deaths
      and morbidity to assess the effect of BUP on public health, (2) the patient limit
      for group practices should apply to individual physicians rather than group
      practices, (3 and 4) telephone and Internet-based physician and pharmacist
      support is needed, (5) clinicians who provide psychosocial services to opioid
      dependent patients should be informed of the role of BUP, (6) opioid-dependent
      patients should be instructed to present for induction in mild withdrawal, (7)
      the existing Center for Substance Abuse Treatment guidelines provide a reasonable
      induction protocol, (8) physicians should be prepared to use ancillary
      medications with BUP induction, (9) a physician or nurse must be available to the
      patient during the induction period, (10) concurrent counseling and support
      services are necessary, (11) detoxification without appropriate followup
      addiction treatment leads to rapid relapse and is not as effective as
      maintenance, (12) pregnant opioid-dependent women should be treated using good
      clinical practice including specialist addiction care and prenatal care, (13) BUP
      induction and withdrawal treatment may benefit from different designations for
      payment, (14) take-home medication options should be tailored to patients' needs,
      (15) there is a need for clinical and policy research in unique patient
      populations.

PMID- 15450649
TI  - Trauma history and relapse probability among patients seeking substance abuse
      treatment.
AB  - We estimated the prevalence of trauma history and relapse in a sample of 959
      patients at two outpatient chemical dependence clinics of a managed healthcare
      organization. A large majority (89%) reported a history of at least one traumatic
      event. The most common traumatic events were serious accidents, being robbed,
      seeing someone killed or seriously injured, and partner violence. One third of
      the patients had a history of substance abuse disorder relapse. There were gender
      and ethnic differences in the types of traumatic events reported. There were
      ethnic differences in relapse rates, which were highest among African American
      and multicultural patients. The types of traumatic events reported differed in
      patients of various sexual orientations. Bisexual patients had the highest rates
      of relapse, even when trauma exposure was controlled. Clinical implications of
      the findings are discussed.

PMID- 15450650
TI  - What aspects of treatment matter to the patient in the treatment of cocaine
      dependence?
AB  - Patient views of the helpful aspects of treatment were examined in the NIDA
      Collaborative Cocaine Treatment Study, a multi-site trial comparing four
      psychosocial treatments: individual cognitive therapy (CT), individual supportive
      expressive dynamic therapy (SE), individual drug counseling, and group drug
      counseling only, for the treatment of cocaine dependence. Factor analysis of the
      items of Helpful Aspects of Treatment measure suggested a general therapy factor,
      a group treatment/education factor, and a treatment structure factor. No
      differences were found among the four treatments on the ratings of helpfulness of
      these three factors, common factors, or drug intervention components. However,
      treatment specific cognitive therapy items (e.g. use of the cognitive model) and
      treatment structure differentiated individual CT from individual SE, and to a
      lesser extent from individual drug counseling. Ratings of helpfulness were
      significantly related to retention and alliance but were largely unrelated to
      changes in drug use or psychiatric outcomes.

PMID- 15450651
TI  - Apertureless scanning near-field fluorescence microscopy in liquids.
AB  - We show that apertureless scanning near-field optical microscopes that use sharp
      vibrating conical tips can be operated in liquid environments. We have
      investigated the damping of the tip oscillation as a function of its shape and as
      a function of its depth under the liquid surface. The degradation of the quality
      factor from 150 in air down to 15 in liquid does not impede to perform
      topographic and optical measurements with a very good sensitivity. As an example
      of application, we present near-field fluorescence images of dye-doped
      polystyrene spheres immersed in a liquid.

PMID- 15450652
TI  - Nanofabrication of cylindrical STEM specimen of InGaAs/GaAs quantum dots for 3D
      STEM observation.
AB  - We demonstrate the multiazimuth observation (360 degrees in principle) of
      InGaAs/GaAs quantum dots (QDs) by means of a 300 kV scanning transmission
      electron microscope (STEM), where both cross-sectional and plan-view observations
      are performed on a single STEM specimen for the first time. A cylindrical
      specimen with a diameter of 200-300 nm including the QD layer inside along the
      rotation axis was fabricated by the focused ion beam (FIB) technique, with the
      application of a newly developed mesa-cutting method to adjust the position and
      angle of the QD layer precisely. The 360 degrees STEM observation is realized by
      mounting the cylindrical specimen on a holder equipped with a specimen-rotation
      mechanism. High potential of 3D-STEM observation is briefly presented by showing
      high contrast images of QDs, dark field images, and moire fringes with various
      incident angles.

PMID- 15450653
TI  - Off-axis electron holography with a dual-lens imaging system and its usefulness
      in 2-D potential mapping of semiconductor devices.
AB  - A variable magnification electron holography, applicable for two-dimensional (2
      D) potential mapping of semiconductor devices, employing a dual-lens imaging
      system is described. Imaging operation consists of a virtual image formed by the
      objective lens (OL) and a real image formed in a fixed imaging plane by the
      objective minilens. Wide variations in field of view (100-900 nm) and fringe
      spacing (0.7-6 nm) were obtained using a fixed biprism voltage by varying the
      total magnification of the dual OL system. The dual-lens system allows fringe
      width and spacing relative to the object to be varied roughly independently from
      the fringe contrast, resulting in enhanced resolution and sensitivity. The
      achievable fringe width and spacing cover the targets needed for devices in the
      semiconductor technology road map from the 350 to 45 nm node. Two-D potential
      maps for CMOS devices with 220 and 70 nm gate lengths were obtained.

PMID- 15450654
TI  - Microscopy, mathematics, measurements and Moses.

PMID- 15450655
TI  - Nanosurgery: observation of peptidoglycan strands in Lactobacillus helveticus
      cell walls.
AB  - The internal cell wall structure of the bacterium Lactobacillus helveticus has
      been observed in situ in aqueous solution using an atomic force microscope (AFM).
      The AFM tip was used not only for imaging but presumably to remove mechanically
      large patches of the outer cell wall after appropriate chemical treatment, which
      typically leaves the bacteria alive. The surface exposed after this "surgery"
      revealed approximately 26 nm thick twisted strands within the cell wall. The
      structure and location of the observed strands are consistent with the glycan
      backbone of peptidoglycan fibers that give strength to the cell wall. The
      structural organization of these fibers has not been observed previously.

PMID- 15450656
TI  - Role of multipole moment of the probe in apertureless near-field optical
      microscopy.
AB  - The model of apertureless near-field optical microscope is developed taking into
      account the multipole moment of probe. In the case of samples with small
      dielectric absorption, the multipole moments are shown to be responsible for the
      appearance of additional resonances in the spectrum of scattered signal. The
      influence of multipole moments is especially pronounced in the near-field
      microscopy with modulation of tip-sample distance. A good agreement of the
      theoretical results with experimental data in the case of resonant interaction of
      the probe and sample is demonstrated.

PMID- 15450657
TI  - Cross-section analysis of organic light-emitting diodes.
AB  - The 'lift-out' technique using a focused ion beam microscope was applied to
      prepare cross-sectional specimens of organic light-emitting diodes for use in
      transmission electron microscopy. The focused ion beam equally thins the
      organic/inorganic hybrid devices despite the difference in material hardness of
      the compounds. This allowed to overcome preparation difficulties of conventional
      techniques such as ion thinning or ultra-microtomy. Two different samples were
      prepared and studied by both conventional transmission electron microscopy and
      analytical electron microscopy to display some of the investigation possibilities
      which become available with this sample preparation method.

PMID- 15450658
TI  - Normalizing projection images: a study of image normalizing procedures for single
      particle three-dimensional electron microscopy.
AB  - In the process of three-dimensional reconstruction of single particle biological
      macromolecules several hundreds, or thousands, of projection images are taken
      from tens or hundreds of independently digitized micrographs. These different
      micrographs show differences in the background grey level and particle contrast
      and, therefore, have to be normalized by scaling their pixel values before
      entering the reconstruction process. In this work several normalization
      procedures are studied using a statistical comparison framework. We finally show
      that the use of the different normalization methods affects the reconstruction
      quality, providing guidance on the choice of normalization procedures.

PMID- 15450659
TI  - APFIM investigations on site occupancies of the ternary alloying elements Cr, Fe,
      and Re in NiAl.
AB  - The site occupancies of the transition metals Cr, Fe, and Re dissolved in NiAl of
      stoichiometric composition have been determined by atomic layer resolved atom
      probe field-ion microscopy (APFIM). The investigations were supported by X-ray
      diffraction studies to evaluate the lattice parameters. These are influenced by
      atomic size effects and constitutional lattice defects like Ni antistructure
      atoms in the Al sublattice and vacancies in the Ni sublattice. The APFIM results
      were compared with ALCHEMI data and calculated site preference energies published
      in the literature. Chromium additions to stoichiometric NiAl with 0.8 at% in
      solid solution exhibit a strong preference for Al sites. The lattice parameter of
      NiAl(Cr) solid solution is decreased. Iron atoms dissolved in higher
      concentrations of 5 at % in NiAl are almost equally distributed within both
      sublattices. They are possessing a weak preference for Al sites, which causes a
      lattice expansion of NiAl(Fe) solid solution. ALCHEMI results and site preference
      energy data show a strong site preference of Cr atoms for the Al sublattice. In
      contrast, iron atoms exhibit a weak site preference for Ni sites depending upon
      the stoichiometry of the NiAl host lattice. Re solutes in low concentrations of
      about 0.2 at % in NiAl possess a strong site preference for the Ni sublattice.
      The increase of the lattice parameter of NiAl(Re) is due to the pronounced size
      effect of Re atoms. For these species no ALCHEMI and site preference energy data
      are available in the literature.

PMID- 15450660
TI  - Coherence and sampling requirements for diffractive imaging.
AB  - Coherent Diffractive Imaging (CDI) allows images to be reconstructed from
      diffraction patterns by solving the non-crystallographic phase problem for
      isolated nanostructures. We show that the Shannon sampling of diffraction
      intensities needed in CDI requires a coherence width about twice the lateral
      dimensions of the object, and that the linear number of detector pixels fixes the
      energy spread needed in the beam. The Shannon sampling, defined by the transform
      of the periodically repeated autocorrelation of the object, is related to Bragg
      scattering from an equivalent crystal, and shown to be consistent with the
      sampling of Young's fringes established by scattering from extreme points in the
      object. The results are relevant to the design of diffraction cameras for CDI and
      plans for femotosecond X-ray diffraction from individual proteins.

PMID- 15450661
TI  - Thermal AFM: a thermopile case study.
AB  - In this work, an atomic force microscope (AFM) with an integrated thermal sensor
      has been used to obtain the local spatial distribution of temperatures in a
      micromachined thermopile with submicron resolution. In this communication, we
      will show how the dimensional, structural and functional characteristics of a
      thermopile suits well with the requirements for AFM thermal imaging, and how a
      deeper insight of the thermopile operation can be gained with the aid of these
      advanced scanning probe-based tools.

PMID- 15450662
TI  - Radiation damage in coronene, rubrene and p-terphenyl, measured for incident
      electrons of kinetic energy between 100 and 200 kev.
AB  - We have measured the sensitivity of three highly conjugated organic compounds to
      electron irradiation. Using a 200 keV TEM, loss of crystallinity was determined
      from quantitative electron-diffraction measurements. Degradation of the molecular
      ring structure was monitored from fading of the 6 eV pi-excitation peak in the
      energy-loss spectrum. Measurements at incident energies between 30 keV and 100 eV
      were made using a scanning electron microscope (SEM), by recording gradual decay
      of the cathodoluminescence (CL) signal. Expressed in Grays, the energy dose
      required for CL decay in coronene is a factor of 30 lower than for destruction of
      crystallinity and a factor of 300 lower than for destruction of the molecular
      structure. Below 1 keV, the CL-decay cross section shows no evidence of a
      threshold effect, indicating that the damage involved is caused by valence
      electron (rather than K-shell) excitation. Therefore even relatively radiation
      resistant organic materials may undergo some form of damage when examined in a
      low-energy electron microscope or a low-voltage SEM.

PMID- 15450663
TI  - Digital atomic force microscope moire method.
AB  - In this study, a novel digital atomic force microscope (AFM) moire method is
      established to measure the displacement and strain fields. The moire pattern is
      generated by the interference between the specimen grating and the virtual
      reference grating formed by digital image processes. The overlapped image is
      filtered by the 2-D wavelet transformation to obtain clear interference moire
      patterns. From moire patterns, the displacement and strain fields can be
      analyzed. The experimental results show that the digital AFM moire method is very
      sensitive and easy to realize in nanoscale measurements.

PMID- 15450664
TI  - Electron-acoustic and surface electron beam induced voltage signal formation in
      scanning electron microscopy analysis of semiconducting samples.
AB  - The conditions for the detection of electron-acoustic (EA) and surface electron
      beam induced voltage (SEBIV) signals using a common sample mount and bottomside
      detection scheme are hereby discussed. It is shown that while the intrinsic
      properties of the sample under electron-beam irradiation would chiefly determine
      the presence of these contrast mechanisms, the manner in which the sample is
      mechanically and electrically configured in relation to the signal detection is
      crucial in determining the actual signal coupling mechanisms at work and hence
      the assumptions by which a robust and consistent interpretation of experimental
      results can be made. EA signals are detectable only if electrical coupling
      between the sample and the detector is defeated, a necessary pre-requisite as the
      signal magnitude of carrier-generated SEBIV coupling is 2-3 orders larger in most
      cases. With regards to SEBIV detection, bottomside SEBIV detection may be
      preferable to topside detection owing to minimization of topographic signal
      contribution, higher signal coupling efficiency and a less complex sample
      detector mounting procedure.

PMID- 15450665
TI  - Investigation of oxide tunnel barriers by atom probe tomography (TAP).
AB  - Oxide tunnel barriers (TMR) are currently of interest for application in magnetic
      sensor and storage devices. Compared to giant magneto resistance (GMR) devices,
      tunnel barriers are distinguished by an improved effect amplitude and a higher
      base resistivity, so that they may be used in 'current perpendicular to plane'
      arrangements. We investigated the nano-structure of such TMR devices using field
      ion microscopy in combination with a 2D-detection setup. Spin valve structures
      consisting of Co and Ni(79)Fe(21) electrodes and Al(2)O(3) barriers were prepared
      by sputter deposition on tips of 30-50 nm radius of curvature suitable for field
      ion microscopy. Inspite of the isolating character of the barrier material, the
      chemical structure can be reasonably characterized by analytical field ion
      microscopy. The 3D spatial distribution of the atomic species, in particular the
      distribution of oxygen, is discussed in dependence on various deposition methods.

PMID- 15450666
TI  - Model based quantification of EELS spectra.
AB  - Recent advances in model based quantification of electron energy loss spectra
      (EELS) are reported. The maximum likelihood method for the estimation of physical
      parameters describing an EELS spectrum, the validation of the model used in this
      estimation procedure, and the computation of the attainable precision, that is,
      the theoretical lower bound on the variance of these estimates, are discussed.
      Experimental examples on Au and GaAs samples show the power of the maximum
      likelihood method and show that the theoretical prediction of the attainable
      precision can be closely approached even for spectra with overlapping edges where
      conventional EELS quantification fails. To provide end-users with a low threshold
      alternative to conventional quantification, a user friendly program was developed
      which is freely available under a GNU public license.

PMID- 15450667
TI  - Surface charge compensation for a highly charged ion emission microscope.
AB  - A surface charge compensation electron flood gun has been added to the Lawrence
      Livermore National Laboratory (LLNL) highly charged ion (HCI) emission
      microscope. HCI surface interaction results in a significant charge residue being
      left on the surface of insulators and semiconductors. This residual charge causes
      undesirable aberrations in the microscope images and a reduction of the time-of
      flight (T-O-F) mass resolution when studying the surfaces of insulators and
      semiconductors. The benefits and problems associated with HCI microscopy and
      recent results of the electron flood gun-enhanced HCI microscope are discussed.

PMID- 15450668
TI  - Tip to substrate distances in STM imaging of biomolecules.
AB  - STM images of single biomolecules adsorbed on conductive substrates do not
      reproduce the expected physical height, which generally appears underestimated.
      This may cause the tip to interfere with the soft biological sample during the
      imaging scans. Therefore, a key requirement to avoid invasive STM imaging is the
      knowledge, and the control, of the initial tip to substrate distance. This is
      connected to the setting of the tunnelling current and applied voltage, which
      define a tunnelling resistance. The height of the STM tip was measured by
      calibrating the tunnelling resistance, as a function of its vertical displacement
      until establishing a mechanical contact. At a tunnelling resistance of 4 x
      10(9)Omega, distances of about 3 and 6 nm are estimated when flat Au substrates
      are imaged in water and in air, respectively. On such a ground, the relevance of
      the starting tip-substrate distance in determining a non-invasive imaging has
      been investigated for a plastocyanin mutant chemisorbed on Au(111) electrodes. At
      tunnelling distances sufficient to overcome the physical height of the imaged
      biomolecules, their lateral dimensions are found to be consistent with the
      crystallography, whereas they are significantly broadened for smaller distances.

PMID- 15450669
TI  - Ultimate performance of objective magnetic lens.
AB  - The current density sigma as a limit technological factor affecting the
      aberrations of magnetic objective lenses, has been studied. A practical form of
      Tretner's (optik 16 (1959) 155) aberration parameters, in terms of current
      density sigma, have been suggested. Iron-free lenses were compared with ironpole
      piece lenses.

PMID- 15450670
TI  - Coherent inelastic scattering in Si and TiAl.
AB  - An image filter has been used to test a simple model describing the dynamical
      scattering of electrons that have suffered multiple interactions with plasmons.
      Semi-quantitative agreement is observed in both Si and TiAl under quasi two-beam
      conditions. In the latter material it is shown that the classical Hirsch, Howie,
      Whelan analysis of contrast due to dislocations can be carried out in images
      produced by electrons that have suffered as many as five interactions with
      plasmons and at thicknesses at which the unfiltered and zero loss images show no
      contrast.

PMID- 15450671
TI  - Elemental mapping using the Ga 3d and In 4d transitions in the epsilon2
      absorption spectra derived from EELS.
AB  - It is proposed that by using the valence-band states in electron energy loss
      spectroscopy, high-spatial resolution maps of quantitative elemental composition
      may be acquired with high acquisition rates. Further, it is shown that by using
      the epsilon(2) spectrum instead of single scattering data, the noise in the
      observed transitions and associated maps is significantly reduced. The epsilon(2)
      spectra are derived through a Kramers-Kronig transformation from electron energy
      loss spectra obtained in a scanning transmission electron microscope. Using
      transitions that occur in the epsilon(2) absorption spectrum (<40eV),
      quantitative elemental maps for III-V device structures have been produced. An
      example is provided using the Ga 3d transition to map a GaInNAs/GaAs laser
      structure. Weaker transitions such as In 4d have also been used to verify the Ga
      elemental distribution.

PMID- 15450672
TI  - Off-axis electron holography without Fresnel fringes.
AB  - A new method for forming an electron hologram without Fresnel fringes caused by
      an electron biprism is presented. Adding a fine filament to the ordinary setup
      for off-axis electron holography directly prevented Fresnel diffraction at the
      electron biprism and eliminated 70% of the phase error due to the Fresnel
      diffraction. This made it possible to obtain a hologram having uniform
      interference fringes, and to reconstruct a clear phase image of a weak electric
      field.

PMID- 15450673
TI  - Comment on "Experimental and theoretical evidence for the magic angle in
      transmission electron energy loss spectroscopy" by H. Daniels, A. Brown, A.
      Scott, T. Nichells, B. Rand and R. Brydson.

PMID- 15450674
TI  - Effects of high cholesterol diet on gliosis in apolipoprotein E knockout mice.
      Implications for Alzheimer's disease and stroke.
AB  - Hypercholesterolemia has been suggested as a risk factor for Alzheimer's disease
      (AD). A genetic risk factor for AD is the E4 allele of apolipoprotein E (apoE).
      ApoE is the major lipoprotein transporter in the brain, and is mainly produced by
      glial cells. The present study is focussed on analysing the effects of high
      cholesterol (HC) diet, duration 9 months, on glial activation in the brain, both
      in wild type (WT) mice and in mice with a null mutation in the apoE gene (knock
      out, KO) mice. The activation of astrocytes and microglia was analysed after
      immunohistochemical labelling of glial fibrillary acidic protein (GFAP), and
      F4/80, respectively. In addition, the expression of the antioxidant enzyme
      NAD(P)H:quinone oxidoreductase (NQO1) was analysed. There was a marked
      stimulation of astrocyte and microglial activation as well as induced expression
      of NQO1 in the hippocampus and cerebral cortex upon HC diet. Furthermore, there
      was significant astrocyte activation in the apoE KO mice, as compared to the WT
      mice, on ND. The long time exposure to HC diet combined with apoE deficiency
      resulted in a synergistic effect on the expression of NQO1 in the brain.

PMID- 15450675
TI  - Nested task constraints shape continuous perception-action coupling control
      during human locomotor pointing.
AB  - Behavioural studies of human locomotor pointing have been dominated by specific
      task constraints of generating maximal approach velocity towards spatial targets.
      To examine locomotor pointing under different nested task constraints, at sub
      maximal approach velocities and with concomitant differences in speed-accuracy
      trade offs, run-ups of professional cricket bowlers (n = 6) were analysed. Inter-
      and intra-trial analyses of step length adjustments revealed how differences
      between current and required locomotor pointing behaviour constrained visual
      adaptations of gait. Results supported a continuous perception-action coupling
      control mechanism, although no relationship was observed between step number in
      sequence and total amount of adjustment made, implying that visual adaptations
      did not continue to the end of a run-up once initiated. Rather, bowlers made step
      adjustments throughout the run-up, with strong associations for amount of
      adjustment made and amount needed. Significant variations were observed in inter
      individual strategies for making most adjustments at different points of the run
      up. A key premise of prospective control models of locomotor pointing was found
      to be robust, since regulation of cricketer's gait was continuous and based on
      perception of current and required behaviour. Findings extend understanding of
      the nature and range of nested task constraints under which perception-action
      coupling controls locomotor pointing performance.

PMID- 15450676
TI  - A study of a topiramate pre-treatment on the effects induced by a subanaesthetic
      dose of ketamine on human reaction time.
AB  - Ketamine, a N-methyl-D-aspartate (NMDA) receptor antagonist, impairs reaction
      time performance and interacts with foreperiod duration, thereby suggesting that
      ketamine alters motor preparation. These effects can be attributed either to the
      blockade of NMDA receptors or to the stimulation of alpha-amino-3-hydroxy-5
      methylisoxasole-4-proprionic acid (AMPA) and kainate receptors. The purpose of
      the present study was: (i) to replicate previous findings and (ii) to study the
      effect of a pre-treatment with topiramate, an AMPA/kainate antagonist, on the
      impairments induced by ketamine on RT. Thirty six healthy subjects (3 groups of
      12) performed a two-choice RT task in which the foreperiod was manipulated. All
      subjects performed the task under perfusion of ketamine (intravenous bolus of
      0.12 mg followed by a perfusion of 0.5 mg/kg over 60 mn) or placebo (saline).
      Depending on the group, an oral dose of topiramate (50 mg) or placebo (lactose)
      was administered 2 h before ketamine infusion (randomised, double-blind, double
      dummy, parallel-group design). At the dose studied, topiramate exerted no
      detectable effect on RT. The results relative to ketamine corroborate previous
      findings and suggest that this molecule affects motor preparation through the
      blockade of NMDA receptors.

PMID- 15450677
TI  - Association between a T/C polymorphism in intron 2 of cholesterol 24S-hydroxylase
      gene and Alzheimer's disease in Chinese.
AB  - A polymorphism (T/C) in intron 2 of the cholesterol 24-hydroxylase (CYP46) gene
      has recently been reported to be associated with the risk for late-onset
      Alzheimer's disease (LOAD). To investigate possible involvement of the CYP46 gene
      and apolipoprotein E (APOE) gene polymorphisms in the manifestation of LOAD, we
      analyzed 99 sporadic LOAD patients and 113 healthy controls of China. We found an
      obvious association between CYP46 TT genotype and LOAD (OR = 2.98, 95% CI 1.64
      5.44, P < 0.001). A clear increase of the risk to develop LOAD was also observed
      in subjects carrying both the CYP46 TT genotype and the APOE epsilon4-allele (OR
      = 12.94, 95% CI 4.26-39.32, P < 0.001). Our data reveal that the polymorphism of
      CYP46 intron 2 is implicated in the susceptibility to LOAD and a strong
      synergistic interaction between CYP46 TT homozoygots and APOE epsilon4 carrier
      status on the risk of LOAD.

PMID- 15450678
TI  - In situ detection of intracerebral cytokine expression after human brain
      contusion.
AB  - The study was undertaken to analyze intracerebral expression of pro- and anti
      inflammatory cytokines after traumatic brain injury (TBI) in man in order to
      compare the findings with previous experimental data regarding the pathogenesis
      of secondary brain injury. Contused brain tissue biopsies were obtained from 12
      consecutive patients undergoing surgery for brain contusions 3 h to 5 days after
      trauma. Cytokine expression was analyzed by in situ hybridization and
      immunohistochemistry. In patients undergoing surgery less than 24 h after trauma,
      strong expression of both the pro-inflammatory cytokines interleukin (IL)-1-beta,
      IL-6 and interferon (IFN)-gamma and the anti-inflammatory cytokine IL-4 was
      detected. In patients undergoing surgery between 3 and 5 days after trauma, IL-4
      expression was significantly lower (P < 0.05) compared to the patients operated
      early. IL-1-beta and IFN-gamma expression remained strong in comparison to IL-6
      and IL-4 expression (P < 0.05). Immunohistochemistry for IL-1-beta confirmed that
      the protein was produced with a temporal and regional pattern that corresponded
      to in situ hybridization results. The study provides in situ data on
      intracerebral cytokine expression after contusion in the clinical setting. Strong
      intracerebral cytokine expression occurs in the perilesional zone both in the
      early and the delayed phase after traumatic brain injury in humans. The temporal
      regulation of pro- and anti-inflammatory cytokines differs which reveals
      different therapeutic windows for pharmacological intervention.

PMID- 15450679
TI  - Effects of salicylate on transient outward and delayed rectifier potassium
      channels in rat inferior colliculus neurons.
AB  - The effects of salicylate (a tinnitus inducer) were studied on the transient
      outward potassium current (I(K(A))) and the delayed rectifier potassium current
      (I(K(DR))) in acutely dissociated rat inferior colliculus neurons by the whole
      cell voltage-clamp method. Salicylate's inhibition of the amplitude of I(K(A))
      and I(K(DR)) was concentration-dependent. The IC(50) values for the blocking
      action of salicylate on I(K(A)) and I(K(DR)) were 2.27 and 0.80 mM, respectively.
      At a concentration of 1 mM, salicylate significantly shifted the activation and
      inactivation curves of I(K(DR)) negatively by approximately 11 and 24 mV,
      respectively, but did not shift the I(K(A)) curves. In conclusion, salicylate
      inhibits both I(K(A)) and I(K(DR)) in rat inferior colliculus neurons but only
      significantly affects the activation and inactivation kinetics of I(K(DR)).
      Depression of I(K(DR)) by salicylate may play an important role in salicylate
      induced tinnitus.

PMID- 15450680
TI  - Acetylcholine release in the hippocampus during the operant conditioned reflex
      and the footshock stimulus in rats.
AB  - The activity of the septo-hippocampal cholinergic pathway was investigated by
      measuring changes in the extracellular acetylcholine (ACh) levels in the
      hippocampus, by means of microdialysis, during the operant conditioned reflex and
      the repeated footshock stimulus. Microdialysis samplings were conducted in a
      Skinner box where lights were delivered as conditioned stimuli (CS) paired with
      footshocks as unconditioned stimuli (US). Two groups of rats were used.
      Extracellular ACh and choline (Ch) in samples collected at 6min intervals were
      assessed by high-performance liquid chromatography with electrochemical
      detection. The elevation of hippocampus ACh was observed in the two experimental
      groups. The increase in ACh during aversive stimulus (footshock) was
      significantly larger and was probably related to the number of footshocks. There
      might be moderate increase in the hippocampal ACh release during the retrieval of
      information. The concentration of choline showed no significant fluctuation in
      the two groups during the whole process. This experiment explored in more detail
      hippocampal cholinergic activity in relation to the two different procedures.

PMID- 15450681
TI  - Tumor suppressor gene TP53 is genetically associated with schizophrenia in the
      Chinese population.
AB  - Schizophrenia is a debilitating mental disorder. The TP53 tumor suppressor gene,
      encoding a phosphoprotein, is a key element in maintaining genomic stability and
      cell apoptosis. Recently, reduced risk of cancer in patients of schizophrenia has
      been reported. Some evidence also suggests the possible implication of TP53 in
      neurodevelopment. In order to examine the role of the TP53 gene in the
      pathogenesis of schizophrenic disorders, we investigated the genetic association
      between a functional polymorphism rs1042522 and schizophrenia by sequencing the
      fragment covering 72Pro> Arg in 701 cases and 695 controls in this work. In
      addition, we studied two other SNPs rs2078486 and rs8064946 by allele-specific
      PCR in the same samples. Though rs1042522 and rs8064946 did not show positive
      association with schizophrenia, we did observe statistically significant
      differences on SNP rs2078486 (P-value = 0.029; OR = 1.21; 95% CI 1.02-1.42) and
      on haplotype CAC (P-value = 0.0068; OR = 1.36; 95% CI 1.09-1.70). These results
      demonstrated that TP53 might play a role in susceptibility to schizophrenia.

PMID- 15450682
TI  - When audition alters vision: an event-related potential study of the cross-modal
      interactions between faces and voices.
AB  - Ten healthy volunteers took part in this event-related potential (ERP) study
      aimed at examining the electrophysiological correlates of the cross-modal audio
      visual interactions in an identification task. Participants were confronted
      either to the simultaneous presentation of previously learned faces and voices
      (audio-visual condition; AV), either to the separate presentation of faces
      (visual, V) or voices (auditive, A). As expected, an interference effect of
      audition on vision was observed at a behavioral level, as the bimodal condition
      was performed more slowly than the visual condition. At the electrophysiological
      level, the subtraction (AV - (A + V)) gave prominence to three distinct cerebral
      activities: (1) a central positive/posterior negative wave around 110 ms, (2) a
      central negative/posterior positive wave around 170 ms, AND (3) a central
      positive wave around 270 ms. These data suggest that cross-modal cerebral
      interactions could be independent of behavioral facilitation or interference
      effects. Moreover, the implication of unimodal and multisensory convergence
      regions in these results, as suggested by a source localization analysis, is
      discussed.

PMID- 15450683
TI  - Midkine and retinoic acid reduce cerebral infarction induced by middle cerebral
      artery ligation in rats.
AB  - The present study investigates the neuroprotective effects of midkine (MK) and
      retinoic acid (RA) against ischemia in the CNS. Primary cortical neurons, derived
      from rat E15 embryos (DIV9), were treated with 9-cis-RA (9cRA), all-trans-RA
      (atRA) or vehicle. Using quantitative PCR, the level of MK mRNA was significantly
      increased at 4h after 9cRA application. The protective effect of RA and MK was
      also investigated in adult Sprague-Dawley rats. 9cRA, atRA, MK, or vehicle was
      injected into the lateral ventricle prior to a 60-min-MCA ligation. Pretreatment
      with 9cRA or MK attenuated cerebral infarction in stroke animals. Application of
      a similar dose of atRA did not reduce the size of infarction. In conclusion, our
      data suggest that 9cRA has neuroprotective effects against ischemia-related brain
      injury which may involve upregulation of midkine.

PMID- 15450684
TI  - Hypothermia modifies the effective CS-US interval in conditioned taste aversion
      in rats.
AB  - Conditioned taste aversion can be acquired when rats experience an unconditioned
      stimulus (US) while anesthetized. In contrast to anesthetics, a hypothermia
      induced comatose state immediately after presentation of a taste conditioned
      stimulus (CS) prevented a taste-illness association at relatively short CS-US
      intervals and potentiated the aversion at longer intervals. Results at shorter CS
      US intervals were explained on the basis of hypothermia's temporally graded
      amnesitc properties. Evidence for conditioning at the longer intervals was
      discussed in relation to slowing down metabolism allowing for associations to be
      formed at CS-US intervals that normally do not result in evidence of
      conditioning. Manipulating body temperature during the CS-US interval was
      demonstrated to alter rats' ability to bridge temporal gaps in associative
      learning.

PMID- 15450685
TI  - Expression and changes of calbindin D-28k immunoreactivity in the ventral horn
      after transient spinal cord ischemia in rabbits.
AB  - We examined ischemia-related changes of calbindin D-28k (CB) immunoreactivity in
      L(7) of the spinal ventral horn after transient spinal cord ischemia in rabbits.
      In the sham-operated group, CB immunoreactivity was not present in the spinal
      ventral horn, but CB immunoreactivity was detectable in the dorsal horn. CB
      immunoreactivity was detectable in the ventral horn at 30 min after ischemia: the
      CB immunoreactivity was found in glial cells identified as astrocytes. At 1 h
      after ischemia, CB immunoreactivity was highest and present at a few somata
      located in the lamina VII as well as many glial cells. CB immunoreactivity was
      lower in the lamina VII at 3 h after ischemia compared to 1 h post-ischemic
      group. By 2 days after ischemia, CB immunoreactivity was decreased in this
      region. In addition, the result of Western blot result showed the pattern of CB
      expression similar to that of immunohistochemistry. In conclusion, the ischemia
      related changes of CB immunoreactivity in neurons and glial cells in the ischemic
      spinal ventral horn in rabbits may be related to modulation of intracellular
      calcium following transient ischemia.

PMID- 15450686
TI  - An electrophysiological investigation of the relationship between conceptual
      fluency and familiarity.
AB  - Brain potentials associated with the manipulation of conceptual fluency in a
      recognition memory paradigm were recorded. Enhanced fluency was associated with
      attenuation of the N400 and an increased rate of subjects' endorsing both studied
      and non-studied items as having been studied ("old" responses) in the recognition
      test. Differences were also found in latencies previously associated with post
      retrieval processing, such that in the setting of enhanced fluency (1) non
      studied items were associated with a positive wave from 800 to 1600 ms and (2)
      items endorsed as "new" were more positive than those endorsed as "old" from 1200
      to 1600 ms. The effects on the N400 may be related to the impact of fluency on
      familiarity, whereas later processing may be involved in the attribution of
      fluency to prior experience.

PMID- 15450687
TI  - Exploratory activity, anxiety, and motor coordination in bigenic APPswe +
      PS1/DeltaE9 mice.
AB  - Bigenic APPswe + PS1/DeltaE9 mice with Abeta plaque formation in neocortex and
      hippocampus were evaluated in three tests measuring exploratory activity. By
      comparison to a non-transgenic group controlled for age and gender, 7-month-old
      APPswe + PS1/DeltaE9 mice spent more time in the open arms and had higher
      open/total entries and duration in the elevated plus-maze, indicative of
      disinhibitory tendencies. On the contrary, the groups did not differ in T-maze
      and open-field tests. Moreover, the motor coordination of the bigenic group was
      equivalent to that of controls in stationary beam, coat-hanger, rotorod, and grip
      strength tests. No mouse displayed neurological signs, such as pathological
      reflexes, myoclonus, or convulsions. The results in the elevated plus-maze test
      are akin to the loss of inhibitory control observed in some patients with
      Alzheimer's disease.

PMID- 15450688
TI  - Acquisition of context-specific adaptation is enhanced with rest intervals
      between changes in context state, suggesting a new form of motor consolidation.
AB  - We previously showed that the saccadic system could be adapted in a context
      specific manner: two different adapted gains could be associated with two
      different context cues, with the gain state switched when the context state was
      switched. This was accomplished by alternating context/adaptation states several
      times over the course of an adaptation session, and assessing saccade gain in
      each context state before and after adaptation. One context cue we studied was
      vertical eye position; an adaptive gain increase was induced with the eyes up 10
      degrees, and an adaptive gain decrease with the eyes down 10 degrees. This
      context cue was only partially effective: there was considerable undesired
      transfer of adaptation from the eyes-down condition (gain-decrease) to the eyes
      up condition (gain-increase), with the result that there was little or no gain
      increase adaptation. One explanation for this is that the two context/adaptation
      states, presented one after the other, interfered with each other. In the present
      study, we tested this hypothesis by interposing one-minute rest intervals between
      each alternation in context/adaptation state. The resulting context-specific
      adaptation is greatly improved (relative to the case when there are no rest
      intervals): both gain-increase and gain-decrease adaptations are stronger and
      occur more rapidly. This effect resembles that found in studies on the
      consolidation of motor learning, although such consolidation is believed to occur
      over much longer time spans (hours rather than minutes).

PMID- 15450689
TI  - No genetic association between polymorphisms in the AMPA receptor subunit GluR4
      gene (GRIA4) and schizophrenia in the Chinese population.
AB  - The glutamatergic dysfunction hypothesis of schizophrenia suggests genes involved
      in glutamatergic transmission as candidates for schizophrenia-susceptibility
      genes. It has recently been reported that some haplotypes in the AMPA receptor
      subunit GluR4 Gene (GRIA4), which is located on chromosome 11q22, are positively
      associated with schizophrenia in the Japanese population. In order to assess the
      role of GRIA4 in schizophrenia, we examined three reported positive SNPs (single
      nucleotide polymorphisms): rs609239, rs641574 and rs659840 at the GRIA4 locus in
      schizophrenic cases (n = 372) and controls (n = 392) of the Chinese population.
      Although we had observed similar allele and genotype frequencies compared with
      that in the Japanese population, no evidence was found for association with the
      disease in the analysis of either single nucleotide polymorphisms (all P-values >
      0.300) or haplotype relative risk (all P-values > 0.088). Our results suggest
      that the three SNPs of GRIA4 are unlikely to play a major role in the
      susceptibility to schizophrenia in the Chinese population.

PMID- 15450690
TI  - Improving the diagnostic criteria and procedures for chronic fatigue syndrome.
AB  - Since the publication of the case definition for chronic fatigue syndrome (CFS)
      in 1988 the diagnostic criteria have been revised twice in the U.S. None of the
      case definitions were derived empirically. As a result, there is concern
      regarding the sensitivity, specificity, and reliability of the criteria. The goal
      of the present study was to identify methods for improving the diagnostic
      criteria for CFS. Three groups of 15 participants each were recruited:
      participants with (1) CFS, (2) major depressive disorder (MDD), and (3) healthy
      controls. Using statistical procedures, three methods for improving the
      diagnostic criteria were explored: identification of new diagnostic symptoms, the
      use of severity ratings for symptomatology, and the identification of
      standardized measures that differentiate cases of CFS from other conditions.
      Results of the present study suggest that these three methods hold promise for
      improving the sensitivity, specificity, and reliability of the diagnostic
      criteria for CFS.

PMID- 15450691
TI  - Event-related P3a and P3b in response to unpredictable emotional stimuli.
AB  - In natural situations, unpredictable events processing often interacts with the
      ongoing cognitive activities. In a similar manner, the insertion of deviant
      unpredictable stimuli into a classical oddball task evokes both the P3a and P3b
      event-related potentials (ERPs) components that are, respectively, thought to
      index reallocation of attentional resources or inhibitory process and memory
      updating mechanism. This study aims at characterising the influence of the
      emotional arousal and valence of a deviant and unpredictable non-target stimulus
      on these components. ERPs were recorded from 28 sites during a visual three
      stimulus oddball paradigm. Unpleasant, neutral and pleasant pictures served as
      non-target unpredictable items and subjects were asked to realize a perceptually
      difficult standard/target discrimination task. A temporal principal component
      analysis (PCA) allowed us to show that non-target pictures elicited both a P3a
      and a P3b. Moreover, the P3b component was modulated by the emotional arousal and
      the valence of the pictures. Thus, the memory updating process may be modulated
      by the affective arousal and valence of unpredictable disturbing stimuli, even if
      the task does not require any explicit emotional categorization.

PMID- 15450692
TI  - Influence of a visual spatial attention task on auditory early and late Nd and
      P300.
AB  - Singhal et al. [Psychophysiology 39 (2002) 236] reported that the amplitude of
      the late negative difference (Nd) and P300 components, generated by a dichotic
      listening task, were decreased in parallel by a simultaneously performed visual
      flying task. In contrast, early Nd was unaffected. To investigate the role of
      covert spatial attention in this pattern of results, we substituted Posner's
      attention switching paradigm for the flying task. Fourteen subjects performed the
      dichotic listening and attention tasks alone and in combination. The results
      showed that only the invalid/valid condition of the Posner task reduced the
      amplitude of the late Nd, while the early Nd was unaffected. Contrary to the
      earlier study, P300 dissociated from the late Nd and its amplitude decreased in
      both the invalid/valid and neutral conditions of the Posner task. We conclude
      that the late Nd is sensitive to some aspect of attention switching and that the
      late Nd and P300 share sensitivity to an amodal system to which the early Nd is
      insensitive. Within this system, the late Nd is differentiated from P300 by its
      narrow sensitivity to attentional processing whereas P300 is sensitive to a
      broader range of processing. These similarities and differences are explained in
      the context of a modified version of Kok's model [Psychophysiology 38 (2001) 557]
      of the determinants of P300 amplitude.

PMID- 15450693
TI  - Emotional disclosure for whom? A study of vagal tone in bereavement.
AB  - Recent investigations have shown little evidence that written disclosure benefits
      bereaved individuals over a control condition. The present study hypothesized
      that the effectiveness of written disclosure for bereavement may be moderated by
      vagal tone, as indexed by respiratory sinus arrhythmia (RSA). Vagal tone has been
      identified as an important individual difference in depression. The present study
      investigated 35 bereaved participants in a longitudinal design, with participants
      writing each week for 3 weeks, and then participating in follow-up sessions 1
      week and 1 month later. As with previous studies, bereaved participants showed
      improvement, although no differential improvement was seen in the emotional
      Disclosure group compared to a Control writing group. As hypothesized, however,
      those participants with the highest RSA benefited most from the written
      disclosure, while RSA level did not predict outcome in the control condition.
      Future research should investigate whether vagal tone moderates the impact of
      written disclosure for non-bereaved individuals.

PMID- 15450694
TI  - Cardiac Vagal Tone, defensiveness, and motivational style.
AB  - Cardiac Vagal Tone has been proposed as a stable biological marker for the
      ability to sustain attention and regulate emotion [Porges, Monographs of the
      Society for Research in Child Development 59 (1994) 167-186]. Vagal tone is a
      physiological index of parasympathetic nervous system influence on the heart that
      has predicted a number of emotional behaviors and styles in infants, children,
      and adults. Little research, however, has sought to explore the link between
      vagal tone and established variables relating to personality and self-regulation.
      In this study, vagal tone was collected during 5-min baseline, stress, and
      recovery periods. Subjects (n = 98) also completed a short form of the Marlowe
      Crowne Social Desirability Scale, the Behavioral Activation and Behavioral
      Inhibition Scales, the Taylor Manifest Anxiety Scale, the Self-Consciousness
      Scale, and the Openness to Experience subscale of the Five Factor Personality
      Inventory. Poorer modulation for vagal tone was associated with greater social
      anxiety, while lower vagal tone across recording periods was associated with
      greater defensiveness and lower behavioral activation sensitivity.

PMID- 15450695
TI  - Effects of repeated electrocutaneous pain stimulation on facial blood flow.
AB  - The purpose of the study was to examine the effects of repeated electrocutaneous
      pain stimulation of the hand on facial blood flow responses in healthy human
      subjects (58 adult women). Finger blood flow, mean arterial blood pressure, and
      heart rate were also monitored. To investigate the influence of psychological
      factors, the subjects' affect states were assessed, and physiological responding
      was explored during cognitive distraction, i.e., when attention was turned away
      from the unpleasant stimulus. Consistently, electrocutaneous stimulation elicited
      vasodilatation in the cheek, together with finger vasoconstriction. This response
      pattern was evident even at non-painful stimulation intensities. The facial blood
      flow response showed habituation across stimulation trials and was largely
      unrelated to systemic cardiovascular changes, affect states, and attentional
      manipulation. These findings indicate (1) that the experimentally induced facial
      blood flow changes are part of a non-specific physiological response pattern
      elicited during noxious stimulation, and (2) that they are not dependent on
      regional (orofacial) stimulation for their occurrence.

PMID- 15450696
TI  - Diabetes meanings among those without diabetes: explanatory models of immigrant
      Latinos in rural North Carolina.
AB  - The prevalence of type 2 diabetes is increasing in the United States,
      particularly among minority individuals. Primary prevention programs for diabetes
      must be designed to address the beliefs of the populations they target. Little
      research has investigated the beliefs of those who do not have diabetes. This
      analysis uses in-depth interviews collected from Latino immigrants, not diagnosed
      with diabetes, living in a rural US community. Structured by the explanatory
      models [EM] of Illness framework, this analysis delineates the EMs of diabetes in
      this community. A significant number of the participants had little knowledge and
      few beliefs about diabetes. The EMs of those with knowledge of diabetes were
      varied, but several beliefs were widely held: (a) diabetes is a serious disease
      that is based on heredity or is inherent in all persons, (b) diabetes can result
      from several factors, including strong emotions and lifestyle characteristics (an
      unhealthy diet, not taking care of oneself), (c) beliefs about strong emotion and
      the importance of blood are related to diabetes causes, symptoms and treatment,
      and (d) a major and undesirable outcome of diabetes is weight loss. These results
      provide information for the design of health programs for the prevention of type
      2 diabetes.

PMID- 15450697
TI  - Cultural competence among physicians treating Mexican Americans who have
      diabetes: a structural model.
AB  - Latinos, who constitute the fastest growing ethnically distinct US group,
      experience disproportionately high rates of type 2 diabetes. At the same time,
      linguistic and economic barriers, differing cultural expectations between
      patients and physicians, provider reactions based on stereotypes, and managed
      healthcare shortfalls limit diabetes care. Such trends highlight physicians' need
      to consider culture in the delivery of effective services. To address these
      issues we investigated predictors of culturally competent actions among a sample
      of 134 practicing San Diego County physicians. They provided demographic
      information and completed questions assessing their cultural knowledge, cultural
      awareness, and culturally competent actions specific to Mexican Americans with
      diabetes. We then developed a structural cultural competence model. Results
      indicated that participation in diverse medical education settings and experience
      in community clinics predicted cultural knowledge. Participation in diverse
      educational settings, Latino ethnicity, bilingual skills, and cultural knowledge
      predicted cultural awareness. An internal medicine specialty predicted less
      cultural awareness. Culturally competent actions were only predicted by cultural
      awareness. Goodness-of-fit statistics supported the overall model's
      acceptability. The number of Mexican Americans physicians see in practice did not
      predict any tested cultural competence dimension. Our model supports a number of
      conclusions. First, knowledge of cultural factors per se and simple exposure to
      Mexican Americans in practice do not directly facilitate culturally competent
      care. Rather, such care is most strongly predicted by recognition that cultural
      factors and awareness of personal biases are important. Results further support
      medical education that does not solely focus on basic information about Mexican
      Americans but also explores provider biases and preconceptions. Diverse
      educational experiences appear particularly helpful in this process. Community
      clinic settings also help practitioners gain cultural knowledge. While Latino
      ethnicity predicted cultural awareness, results also suggest that all physicians
      can take steps towards increasing their cultural competence.

PMID- 15450698
TI  - Effects of nurse follow-up on emergency room revisits: a randomized controlled
      trial.
AB  - The emergency room (ER) is the gatekeeper of the hospital. It receives clients
      seeking help from the health care system, then refers them for necessary further
      care or, discharges them back into the community. A 1-year randomized control
      trial was conducted in an acute general hospital in Hong Kong to see if post-ER
      nurse follow-up helped to change health outcome and health care utilization. The
      intervention group received two follow-up calls from an experienced ER nurse,
      within 1-2 days and 3-5 days after ER discharge. The calls' content and the
      management options decisions were protocol driven. A total of 795 patients
      (intervention group=395, control group=400) completed the study. Bivariate
      analysis shows two significantly different variables between the intervention and
      control groups, improvement of the condition and ER revisit within 30 days. When
      other factors are controlled in a multivariate analysis using logistic
      regression, the effect of the intervention on re-visits to ER within 30 days is
      reversed. Gender, times of attending general practitioner after ER visits, and
      not considering other doctors are risks factors related to a higher chance of re
      visiting ER within 30 days. Those who have an improved health condition and
      higher number of times attending general outpatient after ER visits are
      associated with a lower 30-day ER revisit rate. Nurse telephone follow-ups might
      have sensitized subjects to health care needs. Some subjects tended to use the ER
      as a primary care setting and some were doctor-shoppers. A more structured ER
      transitional model that incoporates nurse telephone follow-up and better
      interfacing between private and public health care sector, primary and tertiary
      care might help to decrease inappropriate ER use.

PMID- 15450699
TI  - Client satisfaction with reproductive health-care quality: integrating business
      approaches to modeling and measurement.
AB  - Health-care managers are increasingly interested in client perceptions of clinic
      service quality and satisfaction. While tremendous progress has occurred,
      additional perspectives on the conceptualization, modeling and measurement of
      these constructs may further assist health-care managers seeking to provide high
      quality care. To that end, this study draws on theories from business and health
      to develop an integrated model featuring antecedents to and consequences of
      reproductive health-care client satisfaction. In addition to developing a new
      model, this study contributes by testing how well Western-based theories of
      client satisfaction hold in a developing, Asian country. Applied to urban,
      reproductive health clinic users in Hanoi, Vietnam, test results suggest that
      hypothesized antecedents such as pre-visit expectations, perceived clinic
      performance and how much performance exceeds expectations impact client
      satisfaction. However, the relative importance of these predictors appears to
      vary depending on a client's level of service-related experience. Finally, higher
      levels of client satisfaction are positively related to future clinic use
      intentions. This study demonstrates the value of: (1) incorporating theoretical
      perspectives from multiple disciplines to model processes underlying health-care
      satisfaction and (2) field testing those models before implementation. It also
      furthers research designed to provide health-care managers with actionable
      measures of the complex processes related to their clients' satisfaction.

PMID- 15450700
TI  - Patient satisfaction and ethnic identity among American Indian older adults.
AB  - Work in the field of culturally competent medical care draws on studies showing
      that minority Americans often report lower satisfaction with care than White
      Americans and recommends that providers should adapt care to patients' cultural
      needs. However, empirical evidence in support of cultural competence models is
      limited by reliance upon measurements of racial rather than ethnic identity and
      also by a near-total neglect of American Indians. This project explored the
      relationship between ethnic identity and satisfaction using survey data collected
      from 115 chronically ill American Indian patients >or=50 years at a Cherokee
      Nation clinic. Satisfaction scores were high overall and comparable to those
      found in the general population. Nevertheless, analysis using hierarchical linear
      modeling showed that patients' self-rated American Indian ethnic identity was
      significantly associated with satisfaction. Specifically, patients who rated
      themselves high on the measure of American Indian ethnic identity reported
      reduced scores on satisfaction with health care providers' social skill and
      attentiveness, as compared to those who rated themselves lower. Significant
      associations remained after controlling for patients' sex, age, education,
      marital status, self-reported health, wait time, and number of previous visits.
      There were no significant associations between patients' American Indian ethnic
      identity and satisfaction with provider's technical skill and shared decision
      making. Likewise, there were no significant associations between satisfaction and
      a separate measure of White American ethnic identity, although a suggestive trend
      was observed for satisfaction with provider's social skill. Our findings
      demonstrate the importance of including measures of ethnic identity in studies of
      medical satisfaction in racial minority populations. They support the importance
      of adapting care to patient's cultural needs, and they highlight the particular
      significance of interpersonal communication for patient satisfaction among
      American Indians. Results will be of special interest to health researchers,
      clinicians, and policy makers working in fields related to minority health.

PMID- 15450701
TI  - Social relationships and allostatic load in Taiwanese elderly and near elderly.
AB  - Despite the increasing evidence linking aspects of the social environment to a
      range of health outcomes, important questions remain concerning the precise
      mechanisms or pathways through which social circumstances exert their influence.
      Biological pathways are one important area of current research interest. Using
      data from the Social Environment and Biomarkers of Aging Study (SEBAS) in Taiwan,
      we examined relationships between social environment characteristics and an index
      of cumulative biological dysregulation ("allostatic load," AL) in near elderly
      (NE) (aged 54-70) and elderly Taiwanese (aged 71+). Longitudinal data on levels
      of social integration and extent of social support were used to predict
      cumulative AL at the final survey year. Linear regression analyses revealed that
      among the NE, presence of a spouse between 1996 and 2000 was associated with
      lower AL in 2000 among men, but not women. Among the elderly, ties with close
      friends and/or neighbors were found to be significantly related to lower AL for
      both men and women. Perceived qualities of these social relationships did not
      show consistent associations with AL. This relatively modest set of significant
      relationships stands in contrast to somewhat stronger patterns of findings from
      studies in Western societies. Cross-cultural differences between Western
      societies and an East Asian society such as Taiwan raise the intriguing
      possibility that contextual, normative influences on social experience affect the
      patterns of association between features of these social worlds and the
      physiological substrates of health.

PMID- 15450702
TI  - Mental health among older adults in Japan: do sources of social support and
      negative interaction make a difference?
AB  - This study addresses the question of whether social support and interpersonal
      strain from different sources (i.e., spouse, children, and other relatives and
      friends) have differential impact on mental health. Data for this research came
      from a national probability sample of 2200 persons aged 60 and over in Japan.
      Structural equation models were evaluated within the context of two types of
      social networks: (a) persons who had a spouse and children (n=1299), and (b)
      those with children only (n=677). Between these two networks, the links among
      social support, negative relations, and mental health were contrasted. The
      effects of various sources of social support and negative interactions on mental
      health vary depending on the specific dimension of mental health as well as the
      nature of social networks. Among older Japanese who are married with children,
      social support from spouse has a greater association with positive well-being
      than social support from children and others. However, cognitive functioning is
      uncorrelated with all sources of positive and negative social exchanges. In
      contrast, among those without a spouse, only greater support from children is
      significantly correlated with higher positive well-being, less distress, and less
      cognitive impairment.

PMID- 15450703
TI  - Short-term effects of moving from public housing in poor to middle-class
      neighborhoods on low-income, minority adults' outcomes.
AB  - This study reports results from a quasi-experimental residential mobility study
      in Yonkers, NY, in which low-income minority families residing in public and
      private housing in high-poverty neighborhoods were randomly assigned via lottery
      to relocate to publicly funded attached rowhouses in seven middle-class
      neighborhoods. One hundred seventy-three Black and Latino families who moved and
      142 demographically similar families who remained in the original high-poverty
      neighborhoods were interviewed approximately 2 years after movers relocated; no
      baseline data were available. Multiple regression analyses controlling for
      individual- and family-level background characteristics revealed that adults who
      moved to low-poverty neighborhoods were less likely to be exposed to violence and
      disorder, experience health problems, abuse alcohol, receive cash assistance, and
      were more likely to report satisfaction with neighborhood resources, experience
      higher housing quality, and be employed, when compared with adults who remained
      in high-poverty neighborhoods. Adults who moved to low-poverty neighborhoods were
      less likely than those who stayed in high-poverty neighborhoods to socialize
      informally with neighbors. No program effects were found on adults' symptoms of
      depression and anxiety. These early program effects inform housing policy
      initiatives for low-income families.

PMID- 15450704
TI  - Preventing long-term welfare receipt: the theoretical relationship between health
      and poverty over the early life course.
AB  - Largely absent in the congressional debate regarding U.S. welfare reform
      reauthorization are policy discussions aimed at preventing long-term welfare use
      for families at risk. This study examines three social science perspectives
      explaining the relationship between early poverty and health as a means to
      understand long-term welfare receipt. Using longitudinal data collected for more
      than 30 years from a cohort of African Americans living in inner-city Chicago, we
      examined whether a social causation, health selection, or bio-social perspective
      best characterized the route to long-term welfare receipt. Results indicated that
      a bio-social perspective provided the best explanation for how early life course
      factors relate to long-term welfare use later in adulthood. Thus, this theory
      merits further study as an explanation for the relationship between health status
      and income. These findings point to the vulnerability of those who are both poor
      and in ill health, and should direct our policies regarding how to best prevent
      long term welfare receipt in future generations.

PMID- 15450705
TI  - The relationships of social participation and community ratings to health and
      health behaviors in areas with high and low population density.
AB  - Previous studies have linked social participation and community levels of trust
      with improved health status. We examined the associations between levels of
      community participation, self-reported community ratings (trust), and health
      within a public health surveillance survey conducted in Kansas (N=4601).
      Independent variables were individual ratings of their communities (excellent,
      very good, good/ fair, poor), and their involvement in community groups or
      organizations in the last 5 years (yes/no). Dependent variables were self-rated
      health status, depressive symptoms, physical activity, smoking, obesity, and
      binge drinking. After controlling for age, gender, race/ethnicity, education, and
      having a medical doctor, self-rated health status (p<0.001) and physical activity
      (PA) (p<0.001) were positively, and smoking (p<0.001) and depressive symptoms
      (p<0.001) were negatively associated with community ratings. Only PA (p<0.001)
      remained associated with community involvement in a multivariate analyses.
      Multilevel analysis using county-level data showed no significant interactions
      between population density and dependent variables. Individuals from rural areas
      had the highest community involvement but relatively low levels of community
      ratings. Our findings suggest that individuals in rural areas, especially in
      densely settled rural areas, may face increased risks of poor health.

PMID- 15450706
TI  - Foreign direct investment and trade in health services: a review of the
      literature.
AB  - Globalization is a key challenge facing health policy-makers. A significant
      aspect of this is direct trade in health services, a result of the rise of
      transnational corporations, challenges in health care financing, porous borders
      and improved technology creating the scope for increased 'foreign direct
      investment' (FDI) in health care. This has gathered momentum with the General
      Agreement on Trade in Services (GATS), which aims to further liberalize trade in
      services, and within which FDI has been noted as perhaps the most critical area
      for trade negotiation. Given the rapid development of this area, there are little
      empirical data. This paper therefore seeks to provide the first comprehensive and
      systematic review of evidence concerning FDI and health services. This process
      included electronic bibliographic database searches, website searches and
      correspondence with experts in the area of trade in health services, from which
      76 papers, books and reports were reviewed. Perhaps due to the rapid developments
      in this area, most of the literature is speculative, polarized between those
      arguing for the benefits of liberalization and those arguing against. However,
      there seem to be three issues which emerge as of most importance: (i) the extent
      to which a national health system is commercialized per se is of more
      significance than whether investment in it is foreign or domestic; (ii) the
      national regulatory environment and its 'strength' will significantly determine
      the economic and health impact of FDI, the effectiveness of safeguard measures,
      and the stability of GATS commitments; and (iii) any negotiations will depend
      upon parties having a common understanding of what is being negotiated, and the
      interpretation of key definitions is thus critical. Each of these issues is
      explored in some depth, with the overall conclusion that countries should take a
      step back and first think through the risks and benefits of commercialization of
      their health sector, rather than being sidetracked in to considering the level of
      foreign investment.

PMID- 15450707
TI  - Death and organ procurement: public beliefs and attitudes.
AB  - While brain death and the dead donor rule (patients must not be killed by organ
      retrieval) have been clinically and legally accepted in the US as a prerequisite
      to organ removal, there is little data about public attitudes and beliefs
      concerning these matters. To examine the public attitudes and beliefs about the
      determination of death and its relationship to organ transplantation, 1351 Ohio
      residents >or=18 years were randomly selected and surveyed using random digit
      dialing (RDD) sample frames. The RDD telephone survey was conducted using
      computer-assisted telephone interviews. The survey instrument was developed from
      information provided by 12 focus groups and a pilot study of the questionnaire.
      Three scenarios based on hypothetical patients were presented: brain dead, in a
      coma, or in a persistent vegetative state (PVS). Respondents' provided personal
      assessments of whether the patient in each scenario was dead and their
      willingness to donate that patient's organs in these circumstances. Over 98% of
      respondents had heard of the term brain death, but only one-third (33.7%)
      believed that someone who was brain dead was legally dead. The majority of
      respondents (86.2%) identified the brain dead patient in the first scenario as
      dead, 57.2% identified the patient in a coma as dead (Scenario 2), and 34.1%
      identified the patient in a PVS as dead (Scenario 3). Nearly, a third (33.5%)
      were willing to donate the organs of patients they classified as alive for at
      least one scenario, in seeming violation of the dead donor rule. Most respondents
      were not willing to violate the dead donor rule, although a substantial minority
      was. However, the majority of respondents were unaware, misinformed or held
      beliefs that were not congruent with current definitions of brain death. This
      study highlights the need for more public dialogue and education about brain
      death and organ donation.

PMID- 15450708
TI  - A review of empirical studies on the model of effort-reward imbalance at work:
      reducing occupational stress by implementing a new theory.
AB  - The present study reviews empirical studies of a new occupational stress model of
      effort-reward imbalance at work to examine its validity as an occupational stress
      measure and the theory-based intervention approach to occupational stress
      reduction. The effort-reward imbalance model is valid for demonstrating a
      stressful work environment that reflects the current labor market and predicts
      health conditions among a wide range of working populations. The stressful
      aspects of work measured by the effort-reward imbalance model are different from
      those shown in the job demand-control model, and the adverse health effects are
      independent of each other, which suggests that the two models are complementary.
      The evidence indicates that it is efficient to select psychosomatic symptoms as
      short-range target outcomes and sick leave as a medium-range target outcome of
      the theory-based intervention. In addition, it would be preferable to
      simultaneously measure job satisfaction, morale, motivation, and performance as
      organizational level outcomes. Although employees engaged in diverse occupations
      can be target populations, high effectiveness is expected, particularly in
      service occupations that work shifts. Studies are necessary to determine how long
      and how intensely interventions are implemented. Target work environments are
      selected from the perspective of securing or improving employees' sense of
      fairness and reciprocity by approaching them. Since the theory-based intervention
      depends largely on organizational changes that are beyond the individual
      employees' ability, the cooperation of employers is necessary.

PMID- 15450709
TI  - Prevention of mosquito nuisance among urban populations in Burkina Faso.
AB  - This paper addresses the problems of mosquito control in urban areas of Burkina
      Faso. The main objectives are to examine relevant socio-cultural aspects in
      relation to a mosquito control intervention using a biolarvicide with main
      emphasis on local perceptions of mosquito nuisance and existing practices of
      mosquito control, including the cost of protective measures at household level.
      This is the report of an inter-disciplinary research project carried out in the
      two major towns of Burkina Faso, Bobo-Dioulasso and Ouagadougou, in 1999 and
      2000, respectively. Both quantitative and qualitative methods were used in the
      ethnographic part of the study. Two questionnaire surveys were conducted in both
      study areas: one prior to the intervention (n=1083) and the other after the
      intervention of the treatments with bio-larvicide (n=956). In addition, 70 in
      depth interviews and 17 focus group discussions (FGDs) were conducted. The
      findings show that mosquitoes are considered an important problem in the urban
      areas, both as a nuisance and a health risk and that the local population is very
      active in applying mosquito control measures at the household level. The
      intervention project was received positively by the local population with a
      decline in the perceived level of annoyance. The causal relationship between
      mosquitoes and malaria is clear, but the explanatory framework of the
      relationship between mosquitoes and other diseases is still under debate. The
      most common prevention methods are mosquito coils and aerosol spray, even though
      bed nets are perceived to be the most efficient and effective method. The
      investments in coils and aerosol sprays alone would mean an increase of 40% in
      the national figures for health expenditure at household level.

PMID- 15450710
TI  - Violence against women in Ghana: a look at women's perceptions and review of
      policy and social responses.
AB  - This study examines violence against women in Ghana and how it affects and is
      perceived by them. It looks at violence as experienced by Ghanaian women of
      varying ages, socio-economic status and professional standing. It defines
      domestic violence as violence intentionally perpetrated by husbands or male
      partners--people known to be intimate associates. Domestic violence is approached
      from a multidimensional perspective by examining the multiple facets of violence
      against women: sexual, socio-economic, cultural, pseudo-religious and mental
      torture. Women's perceptions of their rights, responsibilities, duties and abuses
      or violations are evaluated using open-ended qualitative questions in two major
      cities in Ghana: Accra and Kumasi. Policy responses to domestic violence are then
      examined by first reviewing what provisions exist in the country's constitution
      to address the problem and then the specific steps the government itself has
      taken. Civil society's response in the form of activities by non-governmental
      organizations is also reviewed. Finally, the effects of domestic violence on
      women's health and well-being are examined and suggestions for addressing the
      problem are made.

PMID- 15450711
TI  - Geographical proximity and health care utilization in veterans with SCI&D in the
      USA.
AB  - In the USA, substantial geographic variation in health care utilization exists in
      the Department of Veterans Affairs (VA) health care system. Utilization of health
      care services is especially important for veterans with spinal cord injuries and
      disorders (SCI&D) who are often at high risk for secondary complications related
      to their SCI&D. Due to impaired mobility, access to health care for veterans with
      SCI&D may be even more challenging. The goal of this cross-sectional study was to
      describe health care utilization relative to SCI&D veteran residential geographic
      proximity to VA health care facilities. A negative binomial regression model was
      used to examine VA outpatient utilization. Veterans with SCI&D utilized
      outpatient services less frequently when VA facilities were farther away from
      their residences (p<0.000). Female (p<0.000), older (p<0.000), and non-white
      veterans (p<0.000), and veterans with history of respiratory (p<0.000),
      kidney/urinary tract (p<0.005), circulatory (p<0.000), or digestive system
      diseases (p<0.003) were more likely to utilize outpatient care during the study
      period. A Poisson model was used to examine inpatient utilization. Inpatient
      utilization decreased when travel distance to VA facility increased (p<0.000).
      Contrary to outpatient, age did not significantly affect veterans' likelihood of
      using inpatient health care. Marital status, gender, race, and level of injury
      were not related to inpatient utilization. However, history of prior illnesses
      including respiratory (p<0.000), kidney/urinary tract (p<0.000), circulatory
      (p<0.005), digestive system (p<0.015), or skin/subcutaneous tissue/breast-related
      illnesses (p<0.000) were associated with a greater likelihood of inpatient
      utilization. Geographic proximity and other factors on health care use must be
      considered in order to meet the health care demand patterns of veterans with
      SCI&D.

PMID- 15450712
TI  - A review and meta-analysis of formaldehyde exposure and leukemia.
AB  - Most reviews on the carcinogenicity of formaldehyde have focused on cancers of
      the respiratory tract because these cancer sites were thought to be most
      biologically plausible. However, two recent updated large industrial studies have
      found positive associations between some measures of formaldehyde exposure and
      increased leukemia, although another recent update of a large study did not find
      any association. We examine 18 epidemiology studies of workers exposed to
      formaldehyde where leukemia rates were reported. We summarize the findings across
      studies by using meta-analytic techniques to calculate the meta-relative risk
      values (mRR), confidence intervals, and heterogeneity of the risk estimates for
      several study characteristics. We also determine if publication or reporting
      biases may be affecting the estimates. We found a small increase in rate of
      leukemia overall among embalmers (mRR = 1.6, 95%CI 1.2-6.0), and
      pathologists/anatomists (mRR = 1.4, 95%CI 1.0-1.9). Industrial workers, who have
      been reported to have the highest formaldehyde exposures, had a mRR of 0.9 (95%CI
      0.8-1.0). There was increased risk with increasing exposure in two large
      industrial studies, although the increased risk is one of these studies was not
      seen when an external comparison group is used. Also, another large industrial
      study with more highly exposure workers found decreased risk of leukemia among
      the highest exposed group. The long latency for leukemia deaths observed in the
      two industrial studies that reported increased risk was not consistent with a
      chemical carcinogen such as benzene. We found limited evidence of publication or
      reporting bias. On balance, these data do not provide consistent support for a
      relationship between formaldehyde exposure and leukemia risk.

PMID- 15450713
TI  - The implausibility of leukemia induction by formaldehyde: a critical review of
      the biological evidence on distant-site toxicity.
AB  - Formaldehyde is a naturally occurring biological compound that is present in
      tissues, cells, and bodily fluids. It is also a potent nasal irritant, a
      cytotoxicant at high doses, and a nasal carcinogen in rats exposed to high
      airborne concentrations. The normal endogenous concentration of formaldehyde in
      the blood is approximately 0.1 mM in rats, monkeys, and humans, and it is 2- to 4
      fold higher in the liver and nasal mucosa of the rat. Inhaled formaldehyde enters
      the one-carbon pool, and the carbon atom is rapidly incorporated into
      macromolecules throughout the body. Oxidation to formate catalyzed by glutathione
      dependent and -independent dehydrogenases in nasal tissues is a major route of
      detoxication and generally precedes incorporation. The possibility that inhaled
      formaldehyde might induce various forms of distant-site toxicity has been
      proposed, but no convincing evidence for such toxicity has been obtained in
      experimental studies. This review summarizes the biological evidence that
      pertains to the issue of leukemia induction by formaldehyde, which includes: (1)
      the failure of inhaled formaldehyde to increase the formaldehyde concentration in
      the blood of rats, monkeys, or humans exposed to concentrations of 14.4, 6, or
      1.9 ppm, respectively; (2) the lack of detectable protein adducts or DNA-protein
      cross-links (DPX) in the bone marrow of normal rats exposed to [3H]- and
      [14C]formaldehyde at concentrations as high as 15 ppm; (3) the lack of detectable
      protein adducts or DPX in the bone marrow of glutathione-depleted (metabolically
      inhibited) rats exposed to [3H]- and [14C]formaldehyde at concentrations as high
      as 10 ppm; (4) the lack of detectable DPX in the bone marrow of Rhesus monkeys
      exposed to [14C]formaldehyde at concentrations as high as 6 ppm; (5) the failure
      of formaldehyde to induce leukemia in any of seven long-term inhalation bioassays
      in rats, mice, or hamsters; and (6) the failure of formaldehyde to induce
      chromosomal aberrations in the bone marrow of rats exposed to airborne
      concentrations as high as 15 ppm or of mice injected intraperitoneally with
      formaldehyde at doses as high as 25 mg/kg. Biological evidence that might be
      regarded as supporting the possibility of leukemia induction by formaldehyde
      includes: (1) the detection of cytogenetic abnormalities in circulating
      lymphocytes in seven studies of human subjects exposed to ambient concentrations
      in the workplace (but not in seven other studies of human subjects or in rats
      exposed to 15 ppm); (2) the induction of leukemia in rats in a single
      questionable drinking water study with formaldehyde concentrations as high as 1.5
      g/L (but not in three other drinking water studies with concentrations as high as
      1.9 or 5 g/L); (3) the detection of chromosomal aberrations in the bone marrow of
      rats exposed to very low concentrations of formaldehyde (0.4 or 1.2 ppm) (but not
      in another study at concentrations as high as 15 ppm); and (4) an apparent
      increase in the fraction of protein-associated DNA (assumed to be due to DPX) in
      circulating lymphocytes of humans exposed to ambient concentrations in the
      workplace (1-3 ppm). This evidence is regarded as inconsequential for several
      reasons, including lack of reproducibility, inadequate reporting of experimental
      methods, inconsistency with other data, or insufficient analytical sensitivity,
      and therefore, it provides little justification for or against the possibility
      that inhaled formaldehyde may be a leukemogen. In contrast to these inconclusive
      findings, the abundance of negative evidence mentioned above is undisputed and
      strongly suggests that there is no delivery of inhaled formaldehyde to distant
      sites. Combined with the fact that formaldehyde naturally occurs throughout the
      body, and that multiple inhalation bioassays have not induced leukemia in
      animals, the negative findings provide convincing evidence that formaldehyde is
      not leukemogenic.

PMID- 15450714
TI  - Formaldehyde and leukemia: an improbable causal relationship.
AB  - Formaldehyde has been the subject of numerous toxicological and epidemiological
      investigations for almost 25 years. Though most toxicology studies have focused
      on the effects of the chemical on the nasal tract and respiratory system,
      epidemiology investigations have been more extensive evaluating the association
      between formaldehyde and cancers not only of the nasal cavities, nasopharynx, and
      lung, but also of the brain, prostate, pancreas, and hematopoietic system.
      Recently, three studies have been published which report on the possible
      association between exposure to formaldehyde and an increased incidence of
      leukemia, specifically myeloid leukemia. The article summarizes the results of
      these three studies, evaluates the evidence for causality based on recognized
      epidemiologic criteria, and provides an assessment that the association between
      formaldehyde and the increased incidence of leukemia reported in these studies is
      not plausible.

PMID- 15450715
TI  - Reevaluation of mortality risks from leukemia in the formaldehyde cohort study of
      the National Cancer Institute.
AB  - OBJECTIVE: To determine whether the National Cancer Institute's (NCI) recent
      suggestion of a causal association between formaldehyde exposure and mortality
      from leukemia and myeloid leukemia (ML) is robust with respect to alternative
      characterizations and categorizations of formaldehyde exposure and to alternative
      methods of data analysis. METHODS: The original authors provided the cohort data.
      We computed US and local county rate-based standardized mortality ratios (SMRs)
      and internal cohort rate-based relative risks (RR) by categories of four
      formaldehyde exposure metrics (highest peak, average intensity (AIE), cumulative,
      and duration), using both NCI categories and an alternative categorization based
      on tertiles of deaths from all leukemia among exposed subjects. For highest peak
      exposure, we computed RRs by the duration of time worked in the highest peak
      category and the time since highest peak exposure. For AIE, we computed RRs by
      the duration of exposure and the time since first exposure. RESULTS: Our external
      comparisons revealed that the elevated leukemia and ML RRs and associated trends
      reported by NCI for highest peak and AIE occurred because null (or slight) to
      moderate mortality excesses were compared with statistically significant baseline
      category deficits in deaths. Our alternative categorization of AIE yielded
      leukemia and ML SMRs close to 1.0 in the highest exposure category, and revealed
      weaker evidence of a trend in RRs for leukemia and ML. We corroborated NCI's
      finding of no association for cumulative and duration of formaldehyde exposure.
      We found no consistent evidence that leukemia or ML risks increased with
      increasing duration of time spent in a given highest peak exposure (or for AIE,
      duration of exposure in a given AIE category). We also found no consistent
      evidence that leukemia or ML risks were greater in the more relevant shorter
      (less than 20 years) versus longer (20+ years) periods of time from the first
      highest peak exposure (or for AIE, first exposure). CONCLUSIONS: Our reanalysis
      provided little evidence to support NCI's suggestion of a causal association
      between formaldehyde exposure and mortality from leukemia and ML. NCI's key
      findings for highest peak exposure and AIE do not adequately account for the
      inordinately large deficits in deaths in the categories used as the baselines for
      internal rate-based RRs. The NCI findings also do not adequately account for the
      duration of time subjects spent in the highest peak category (or for AIE,
      duration of exposure) or the time since their first peak exposure (or for AIE,
      time since first exposure). Our finding that NCI's suggestion of a causal
      association is not robust with respect to alternative categorizations of
      formaldehyde exposure and methods of data analysis casts considerable additional
      uncertainty regarding the validity of this suggested association.

PMID- 15450716
TI  - Contribution of PCB exposure from fish consumption to total dioxin-like dietary
      exposure.
AB  - Polychlorinated biphenyls (PCB) are the second greatest cause of fish advisories,
      and are often the greatest contributors to dioxin-like toxic equivalency (TEQ) in
      fish and seafood. Because fish consumption is associated with both contaminant
      risks and health benefits, incremental health risks from PCBs in fish should be
      considered within the context of overall TEQ associated dietary risk to enable
      consumers to make informed decisions about choosing to eat fish or alternate
      foodstuffs. In this paper, potential TEQ exposure from PCBs in fish for adults
      with a variety of consumption patterns and consuming fish from a variety of
      sources are calculated using recent consumption and fish contaminant data from
      the literature and compared to total TEQ exposure from all sources. For high
      level consumers and individuals eating fish from relatively contaminated sites,
      PCB TEQ exposure from fish consumption alone may exceed the 1 pg TEQ/kg/day
      average adult daily intake estimated by EPA, which itself carries an upper bound
      cancer risk of 1 in 1000. PCB TEQ risk for average consumers of commercial fish
      is expected to be far less, but is highly uncertain, since there is a dearth of
      congener specific PCB data for commercial fish and seafood.

PMID- 15450717
TI  - Development of an occupational exposure limit for n-propylbromide using benchmark
      dose methods.
AB  - This paper presents the development of an occupational exposure level (OEL) for n
      propylbromide (nPB) using benchmark dose methods. nPB is a non-ozone depleting
      solvent, proposed under the Significant New Alternatives Policy (SNAP) for use as
      a precision vapor degreaser. OELs have generally been developed on the basis of a
      NOAEL or LOAEL and application of uncertainty factors; this paper represents a
      departure from historic methods. Six recently completed toxicological studies
      were critically reviewed to identify (1) toxicologically significant endpoints,
      (2) dose-response information on these endpoints, and (3) uncertainties and
      limitations associated with the studies. Dose-response data were compiled and
      entered into the USEPA's benchmark dose software for calculation of a benchmark
      dose (BMD) and a benchmark dose low (BMDL). Once values were estimated for all
      relevant studies, they were then incorporated into a weight-of-evidence approach
      to develop a single BMD and BMDL representative of nPB. This approach is similar
      to that recently taken by USEPA to develop their own recommended OEL for nPB.
      USEPA's approach is compared and contrasted with ours, particularly in relation
      to the application of uncertainty factors (UFs) to generate a final OEL. There
      are no published criteria for application of UFs in developing an OEL. Although
      USEPA recommends utilizing a UF of 9, based on intraspecies variability and
      pharmacokinetic differences between rats and humans, to meet the goal of
      protecting healthy adult in a workplace setting, no uncertainty factor was deemed
      necessary for nPB in this paper. Therefore, the BMDL was recommended as the OEL.

PMID- 15450718
TI  - Risk assessment of oral exposure to diisononyl phthalate from children's
      products.
AB  - Dialkyl phthalates are plasticizers used in household products made from
      polyvinyl chloride (PVC). Diisononyl phthalate (DINP) is the principal phthalate
      in soft plastic toys. Because DINP is not tightly bound to PVC, it may be
      released when children mouth PVC products. The potential chronic health risks of
      phthalate exposure to infants have been under scrutiny by regulatory agencies in
      Europe, Canada, Japan, and the U.S. This report describes a risk assessment of
      DINP exposure from children's products, by the U.S. Consumer Product Safety
      Commission (CPSC) staff. This report includes the findings of a CPSC Chronic
      Hazard Advisory Panel (CHAP) which: (1) concluded that DINP is unlikely to
      present a human cancer hazard and (2) recommended an acceptable daily intake
      (ADI) level of 120 microg/kg-d, based on spongiosis hepatis in rats. The risk
      assessment incorporates new measurements of DINP migration rates from 24 toys and
      a new observational study of children's mouthing activities, with a detailed
      characterization of the objects mouthed. Probabilistic methods were used to
      estimate exposure. Mouthing behavior and, thus, exposure depend on the child's
      age. Approximately 42% of tested soft plastic toys contained DINP. Estimated DINP
      exposures for soft plastic toys were greatest among children 12-23 months old.
      The mean exposure for this age group was 0.08 (95% confidence interval 0.04-0.14)
      microg/kg-d, with a 99th percentile of 2.4 (1.3-3.2) microg/kg-d. The authors
      conclude that oral exposure to DINP from mouthing soft plastic toys is not likely
      to present a health hazard to children. The opinions expressed by the authors
      have not been reviewed or approved by, and do not necessarily reflect the views
      of, the U.S. Consumer Product Safety Commission. Because this material was
      prepared by the authors in their official capacity, it is in the public domain
      and may be freely copied or reprinted.

PMID- 15450719
TI  - Acute toxicity and cancer risk assessment values for tert-butyl acetate.
AB  - tert-Butyl acetate (TBAc) is an industrial chemical with potential uses as a
      degreaser and in architectural coatings. Limited chronic toxicity data exist for
      TBAc. However, acute inhalation exposure data are available for TBAc.
      Additionally, TBAc has been demonstrated to be substantially metabolized to tert
      butanol (TBA) in rats, and a positive TBA genotoxicity study suggests that TBA
      may cause oxidative DNA damage. TBA has been shown to induce tumors in both rats
      and mice, and the Office of Environmental Health Hazard Assessment has calculated
      an oral cancer potency factor (CSF) for TBA of 3 x 10(-3)(mg/kg-day)(-1).
      Therefore, TBAc should be considered to pose a potential cancer risk to humans
      because of the metabolic conversion to TBA. An acute 1-h reference exposure level
      of 1 mg/m3 can be calculated from the extrapolated no observed adverse effect
      level of 50 mg/m3. A CSF of 0.002(mg/kg-day)(-1) can be derived for TBAc,
      assuming 100% metabolism of TBAc to TBA. An inhalation unit risk value for TBAc
      of 4 x 10(-7)(microg/m(3))(-1) can then be derived from the CSF value for TBAc by
      assuming a human breathing rate of 20 m3/day, 70% fractional absorption, and an
      average human body weight of 70 kg.

PMID- 15450720
TI  - A comparison of microbial dose-response models fitted to human data.
AB  - A study of eight mathematical dose-response models for microbial risk assessment
      was conducted using infectivity and illness data on a variety of microbial
      pathogens from published studies with human volunteers. The purpose was to
      evaluate variability among the models for human microbial dose-response data in
      order to determine whether two-parameter models might suffice for most microbial
      dose-response data or whether three-parameter models should generally be fitted.
      Model variability was measured in terms of estimated ED01s and ED10s, with the
      view that these effective dose levels correspond to the lower and upper limits of
      the 1-10% risk range generally recommended for establishing benchmark doses in
      risk assessment. An investigation of the ranks of the ED01 and ED10 values among
      the models led to the conclusion that the two-parameter models captured at least
      as much uncertainty as the three-parameter models for the data examined. A
      further evaluation of the two-parameter models did not result in the selection of
      one "best" model, but it did provide some insights into the models' relative
      behavior. The model uncertainty analysis proposed by Kang et al. [Regulat.
      Toxicol. Pharmacol. 32 (2000) 68] using four two-parameter models was reinforced.

PMID- 15450721
TI  - Molecular radiation biology/oncology.

PMID- 15450722
TI  - Repair and chromosomal damage.
AB  - Chromosomal aberrations in somatic cells link DNA damage with radiation-induced
      cell killing and individual susceptibility to oncogenesis, and are also potential
      markers of cancer susceptibility. While there is general acceptance that the DNA
      double-strand break (DSB) is the principal initiating lesion the complexity of
      the relationship between the induced frequency and the rates of repair and
      misjoining of DSB, and the production of chromosome and chromatid aberrations has
      led to much controversy. The principal models of chromosome aberrations are: the
      classical 'breakage-and-reunion' or 'breakage-first' model of Sax [Genetics 25
      (1940) 41-68], the 'mis-recombination' model of Chadwick and Leenhouts [Mutat Res
      404 (1998) 113-117] and the 'transcription-based' model of Radford [Int J Radiat
      Biol 78 (2002) 1081-1093]. Chromatid aberrations have also been variously
      interpreted on the 'breakage-first model', Revell's 'exchange' model [Proc R Soc
      B 150 (1959) 563-589] and the 'signal' model [Int J Radiat Biol 73 (1998) 243
      251]. Recent evidence argues strongly for different mechanisms for chromosome
      (formed in G1 or Go) and chromatid (formed in G2) aberrations, i.e. there is
      little or no correspondence in the relative frequencies between chromosome and
      chromatid aberrations. The balance of evidence indicates that chromosome
      aberrations may be formed by a breakage-first type mechanism. Elevated
      frequencies of chromosomal aberrations occur to various extents in cell lines
      mutated in genes involved in both non-homologous DSB end-joining and homologous
      recombinational rejoining of DSB. Chromatid breaks, seem to be formed by a more
      complex mechanism since there is a lack of correspondence between the rates of
      DSB rejoining and chromatid break 'disappearance' (assumed by some to represent
      DSB repair). Thus, a model based on the dissociation of DSB rejoining from
      chromatid break rejoining is required to explain these data. A substantial
      proportion (approximately 20%) of both spontaneous and induced chromatid breaks
      visibly involve inter-chromatid rearrangements (determined using harlequin
      staining of chromatids). It is postulated that the remaining proportion may also
      involve rearrangements, but within a single chromatid (i.e. intra-chromatid
      rearrangements). Disappearance of chromatid breaks with time is postulated to
      result from the completion of rearrangements, i.e. rather than simply from repair
      of DSB.

PMID- 15450723
TI  - Targeting the epidermal growth factor receptor in radiotherapy: radiobiological
      mechanisms, preclinical and clinical results.
AB  - BACKGROUND AND PURPOSE: Inhibition of the epidermal growth factor receptor (EGFR)
      is a fastly developing field in preclinical and clinical cancer research. This
      review presents the current status of knowledge and discusses radiobiological
      mechanisms which may underly the efficacy of EGFR inhibitors combined with
      irradiation. MATERIALS AND METHODS: Preclinical and clinical results on combined
      targeting of the EGFR and irradiation from the literature and from this
      laboratory are reviewed. Focus is given to the radiobiological rationale of this
      approach and to endpoints of experimental radiotherapy. RESULTS: Overexpression
      of the EGFR is associated with decreased local tumour control after radiotherapy,
      especially when the overall treatment time is long. Inhibition of the EGFR either
      alone or in combination with irradiation decreases the growth rate of tumours
      expressing this receptor. Preclinical data provide proof-of-principle that local
      tumour control may be improved by combining irradiation with C225 mAb. In a
      randomised phase III clinical trial, simultaneous irradiation and treatment with
      the EGFR antibody Cetuximab (Erbitux; C225) in head and neck cancer patients
      resulted in significantly improved locoregional tumour control and survival
      compared to curative irradiation alone. Acute skin reactions increased in the
      experimental arm. The underlying mechanisms of enhanced radiation effects of
      combined EGFR inhibition with irradiation and of the partly conflicting results
      in different studies are poorly understood. There is increasing evidence, that
      important intertumoral heterogeneity in the response to EGFR inhibition alone and
      combined with irradiation exists, which appears to be at least partly dependent
      on specific mutations of the receptor as well as of molecules that are involved
      in the intracellular signal transduction pathway. CONCLUSIONS AND OUTLOOK:
      Further investigations at all levels of the translational research chain
      exploring the mechanisms of EGFR inhibition in the context of radiotherapy are
      needed to fully exploit the potential of such combinations and to develop
      predictive tests that direct their use.

PMID- 15450724
TI  - Radiation-induced activation of a common variant of EGFR confers enhanced
      radioresistance.
AB  - BACKGROUND AND PURPOSE: The type-III EGFR variant (EGFRvIII) is known to promote
      enhanced tumorigenicity. We have previously defined the importance of EGFRvIII in
      cellular radiation responses using Chinese hamster ovary cells (CHO). In the
      current study, we have extended our investigations of EGFRvIII to human tumor
      cells in vitro and in vivo and further verified the important role of EGFRvIII in
      modulating radiosensitivity. MATERIAL AND METHODS: The cell lines MDA-MB-231, U
      87 MG, A-431 and U-373 MG were used. Adenoviral (Ad) vectors were produced to
      overexpress EGFRvIII in vitro or in xenograft tumors in vivo. The EGFR, EGFRvIII
      expression and tyrosine phosphorylation (Tyr-P) levels were quantified by Western
      blotting. The relative radiosensitivities were assessed in vitro by standard
      colony formation and in vivo by tumor growth delay assays. RESULTS: The presence
      of EGFRvIII was verified in all xenograft tumors tested with no detectable
      expression in the corresponding cells under in vitro culture conditions. MDA-MB
      231 xenograft tumors demonstrated EGFRvIII expression levels, which were 1.9-fold
      higher relative to EGFRwt compared to a 14.5-fold higher Tyr-P. Ionizing
      radiation of these tumors at 4 Gy induced an average 3.2-fold increase in
      EGFRvIII Tyr-P. EGFRvIII expression in U-373 MG cells significantly enhanced
      survival after 4Gy, which was completely abolished by dominant-negative EGFR
      CD533. Finally, the ability of EGFRvIII to accelerate tumor growth during
      irradiation was confirmed in vivo. CONCLUSION: EGFRvIII is frequently expressed
      in a variety of different tumor types and can confer significant radioresistance,
      thus further providing evidence for EGFRvIII as an additional important target in
      our approaches to radiosensitize malignant solid tumors.

PMID- 15450725
TI  - Molecular profiles as predictive marker for the effect of overall treatment time
      of radiotherapy in supraglottic larynx squamous cell carcinomas.
AB  - BACKGROUND AND PURPOSE: Reduction of the overall treatment time of radiotherapy
      increases the probability of local tumour control, but it does not benefit all
      patients. Identification of molecular marker profiles may aid in the selection of
      patients likely to benefit from accelerated radiotherapy. PATIENTS AND METHODS:
      Two hundred and nine patients with SCC of the supraglottic larynx received
      primary radiotherapy in the randomised DAHANCA trials to 66-68 Gy, 2 Gy/fx but
      with different overall treatment times of 9.5 week, 6.5 week and 5.5 week.
      Formalin-fixed paraffin embedded tumour slides were assessed by
      immunohistochemistry for expression of EGFr, E-cadherin, KI-67 and Bcl-2 and the
      TP53 mutation profile was determined using PCR-amplification, DHPLC and
      sequencing. The profiles were established using a hierarchical clustering
      algorithm with a Bayesian information criterion for cluster number optimisation.
      RESULTS: Full data-set were available for 158 patients and four almost equally
      sized clusters were identified. One of these clusters differed significantly with
      respect to local control compared to the other clusters: the cluster (n=36)
      characterised by wild type TP53, low expression of E-cadherin and Bcl-2, moderate
      KI-67 and EGFr, was not influenced by a reduction in the overall treatment time
      (P=0.6) whereas the other clusters showed an increase in local control when the
      overall treatment time of radiotherapy was reduced. This was also partially seen
      with disease specific survival as the endpoint. CONCLUSIONS: Molecular marker
      profiling may aid in the selection of patients that will benefit of a reduction
      in overall treatment time of radiotherapy in SCC of the supraglottic larynx.

PMID- 15450726
TI  - Effect of reduced EGFR function on the radiosensitivity and proliferative
      capacity of mouse jejunal crypt clonogens.
AB  - BACKGROUND AND PURPOSE: Previous data indicate that the EGFR pathway is involved
      in the response of tumor cell lines to irradiation. To determine if this receptor
      plays a role in the response of the intestinal mucosa, the effect of a
      spontaneous mutation in EGFR (B6C3-a-wa-2) on radiosensitivity and proliferative
      capacity was investigated using in vivo clonogenic assays and
      immunohistochemistry. PATIENTS AND METHODS: EGFR mutant mice were compared with
      wild-type mice using the in vivo jejunal microcolony assay using single and split
      doses to measure the radiosensitivity and repopulation of clonogenic jejunal
      mucosal cells. In addition, paraffin-embedded tissue sections were assessed for
      proliferation (PCNA), DNA repair (Ku70 and gamma H2AX), and apoptosis (TUNEL) by
      immunofluorescent staining (wild-type vs. heterozygous only) at various times
      after 5 Gy single dose. RESULTS: After the high doses used in the split-dose
      experiments, EGFR heterozygous and homozygous mutant mice were significantly more
      radiosensitive than their wild-type littermates. There was no clear difference in
      split-dose repair based on EGFR function. After 5 Gy single dose there were
      significantly more apoptotic cells within the crypts of heterozygous mice than of
      wild-type mice, beginning at 3h post irradiation. Decreased proliferation was
      observed only in the homozygous mutant mice. PCNA staining was lower in the
      heterozygous mice than in wild-type mice at 1 and 3 h post-5 Gy. CONCLUSION: The
      results indicate that after high doses the radiosensitivity of EGFR mutant mice
      is significantly higher than that of wild-type, and that this could be the result
      of an increase in apoptosis rather than reduced DNA repair. Proliferative
      capacity was modestly reduced, but only in the homozygous mutants.

PMID- 15450727
TI  - Irradiation leads to susceptibility of hepatocytes to TNF-alpha mediated
      apoptosis.
AB  - BACKGROUND AND PURPOSE: The pathogenesis of radiation-induced-liver-disease
      (RILD) is still unknown. We tested the hypothesis that irradiated liver
      macrophages influence the viability of radiation stressed hepatocytes. PATIENTS
      AND METHODS: Hepatocytes and liver macrophages were isolated from rat liver,
      cultured and irradiated with doses of 2, 8, and 25 Gy. Cell viability was
      measured by trypan blue exclusion, and by annexin V/propidium iodide staining.
      TNF-alpha in the supernatants from liver macrophage cell culture was
      quantitatively detected by ELISA. TNF-alpha mRNA from liver macrophages was
      measured by real time PCR. RESULTS: Irradiation had no influence on cell
      viability. Apoptosis of irradiated hepatocytes was detected 24h after replacing
      50% of medium with supernatants of irradiated liver macrophages 6 h after
      irradiation (32.0+/-5.8% compared to solely irradiated cells (12+/-2.9%,
      P=0.02)). In supernatants of hepatocytes, no TNF-alpha secretion could be
      measured. A radiation dependent increase was found in supernatants of liver
      macrophages. Addition of anti-TNF-alpha-antibodies to the supernatants of
      irradiated liver macrophages reduced apoptosis (20+/-0.9%). Incubation of
      irradiated hepatocytes with purified recombinant TNF-alpha increased apoptosis in
      irradiated hepatocytes. This effect could be abrogated by additional
      administration of TNF-alpha-antibodies. CONCLUSIONS: Irradiation leads to
      susceptibility of hepatocytes to TNF-alpha mediated apoptosis. Liver macrophages
      may be one of the sources of TNF-alpha in case of liver-irradiation. This cell
      cell-interaction may be an important initial step towards RILD and liver
      fibrosis.

PMID- 15450728
TI  - Transforming growth factor beta 1 dependent regulation of Tenascin-C in radiation
      impaired wound healing.
AB  - BACKGROUND: Following preoperative radiotherapy prior to ablative surgery of
      squamous epithelial cell carcinomas of the head and neck region fibrocontractive
      wound healing disorders occur. Tenascin-C is significantly increased in fibrotic
      tissue conditions and can be stimulated by the transcription factor NF kappa B
      p65. Previous studies showed a reduction of irradiation induced fibrosis during
      the wound healing process by anti-TGF beta(1)-treatment. The aim of the study was
      to clarify the question whether Tenascin-C expression is elevated in radiation
      impaired wounds and whether anti-TGF beta(1)-treatment is capable to influence
      Tenascin-C and NF kappa B expression. MATERIAL AND METHODS: Wistar rats (male,
      weight 300-500 g) underwent preoperative irradiation of the head and neck region
      with 40 Gy, fractionated four times 10 Gy (16 animals), whereas 8 non-irradated
      animals served as a control. Four weeks after irradiation a free myocutaneous
      gracilis flap taken from the groin was transplanted to the neck. Eight animals
      additionally received 5 microg anti-TGF beta(1) into the graft bed by intradermal
      injection prior to each fraction of irradiation and on days 1-7 post-operation.
      On day 14 and 28 following surgery immunohistochemistry (ABC-POX method) was
      performed assessing the cytoplasmic NF kappa B and Tenascin-C staining in the
      transition area between transplant and graft bed. For quantitative considerations
      the labeling index (ratio: positive cells/total cells) was determined. RESULTS: A
      significantly altered expression of Tenascin-C in the preirradiated tissue was
      observed following anti-TGF beta(1)-treatment. NF kappa B protein was upregulated
      in irradiated animals and was significantly reduced in the anti-TGF beta(1)
      treated group on day 28 after transplantation. CONCLUSIONS: Tenascin-C expression
      is prolonged in irradiated animals as compared to non-irradiated tissue. Tenascin
      C seems to be regulated by TGF beta(1) as the application of TGF beta(1)
      neutralizing antibodies reduces Tenascin-C expression. Tenascin-C is a
      potentially useful marker for tissue remodeling due to its restricted
      distribution in adult and healthy tissue and a hallmark for developing fibrosis.

PMID- 15450729
TI  - Inhibitory targeting of checkpoint kinase signaling overrides radiation-induced
      cell cycle gene regulation: a therapeutic strategy in tumor cell
      radiosensitization?
AB  - BACKGROUND AND PURPOSE: The tumor cell defense response to ionizing radiation
      involves a temporary arrest at the cell cycle G(2) checkpoint, which is activated
      by a signaling cascade initiated by the ATM kinase response to DNA damage,
      ultimately leading to the outcome of further cell survival if the DNA is properly
      repaired. The inhibitory targeting of the checkpoint kinase signaling elicited by
      ATM may define a biologically based strategy to override the G(2) phase delay
      that prevents mitotic entry after DNA damage, thereby increasing the probability
      of mitotic cell death following exposure to ionizing radiation. MATERIALS AND
      METHODS: Breast carcinoma cell lines with intact or defective function of the
      tumor-suppressor protein BRCA1 were exposed to ionizing radiation in the absence
      or presence of a specific inhibitor (UCN-01) of the checkpoint kinase CHK1, and
      the response profiles of cell cycle distribution and G(2) phase regulatory
      factors, as well as the efficiency of clonogenic regrowth, were analyzed.
      RESULTS: The radiation-induced G(2) phase accumulation was preceded by a
      transient down-regulation of the G(2) phase-specific polo-like kinase-1 and
      cyclin B1, which required intact function of both BRCA1 and CHK1. The concomitant
      treatment with UCN-01 seemed to amplify the cytotoxic effect of ionizing
      radiation on clonogenic regrowth. CONCLUSION: The effector mechanism of DNA
      damage on cell cycle gene regulation signals through the checkpoint kinase
      network. Among molecular cell cycle-targeted drugs currently in pipeline for
      testing in early phase clinical trials, CHK1 inhibitors may have therapeutic
      potential as radiosensitizers.

PMID- 15450730
TI  - DNA double strand break quantification in skin biopsies.
AB  - BACKGROUND AND PURPOSE: Following induction of double strand breaks the histone
      H2AX is rapidly phosphorylated at regions flanking the breaks resulting in
      nuclear gamma H2AX foci. The purpose of this study was to use this endogenous
      signalling system to quantify the in vivo response to radiation in normal tissue.
      PATIENTS AND METHODS: Skin biopsies were taken from prostate cancer patients
      undergoing radiotherapy with a curative intent. Biopsies were taken at locations
      corresponding to 5 different doses in the range below 1.1 Gy per fraction.
      Biopsies were taken from patients 30 min following the first fraction and then
      once again following the fraction given after the first weekend break in the
      treatment course. The DNA double strand breaks were visualised as gamma H2AX foci
      using immunohistochemistry. Images were acquired using a CCD-camera and a
      fluorescence microscope and the gamma H2AX foci were quantified using digital
      image analysis including the basic procedures of top-hat transformation,
      threshold setting and labelling. RESULTS: Repeated assessments of the biopsies
      showed a high reproducibility in quantifying the number of foci per DNA area of
      the nucleated cells in epidermis. The reproducibility was equally good for the
      two biopsy occasions. A linear dose response was observed for the epidermis in
      the dose region 0-1 Gy. CONCLUSIONS: We have established a method to measure the
      relative amount of DNA double strand breaks by detecting gamma H2AX foci in
      patients exposed to radiotherapy. The method provides a tool to study induction
      and repair of DNA double strand breaks and has the potential to predict
      individual radiosensitivity.

PMID- 15450731
TI  - Breast cancer in female carriers of ATM gene alterations: outcome of adjuvant
      radiotherapy.
AB  - BACKGROUND AND PURPOSE: We analyzed the clinical outcome of breast cancer
      patients carrying sequence variants in the ATM gene who received postoperative
      radiotherapy after breast conservative surgery to test whether an increased
      cellular radiosensitivity may translate into enhanced tumor cell killing and
      thereby result in an improvement of the therapeutic ratio. PATIENTS AND METHODS:
      We investigated a cohort of 138 breast cancer patients who received adjuvant
      radiotherapy following breast conservative surgery for T1 and T2 tumors. Genomic
      DNA samples of these patients had previously been scanned for mutations in the
      ATM gene. Follow-up data were available in 135 patients, with a median follow-up
      of 87 months. Local relapse-free, metastasis-free and overall survival were
      compared between carriers and non-carriers of a sequence variant in the ATM gene.
      RESULTS: Twenty patients were found to carry a sequence variant in the ATM gene
      (truncating, 7; missense, 13). The actuarial 7-year local relapse-free survival
      of carriers vs. non-carriers were 88 vs. 94% (P=0.34). Actuarial metastasis-free
      and overall survival after 7 years were 63 vs. 85% (P=0.01) and 73 vs. 89%
      (P=0.055), respectively. However, the presence of a variant in the ATM gene did
      not remain a significant discriminator for metastasis-free survival in a
      multivariate Cox regression analysis (P=0.068). CONCLUSIONS: Our results do not
      support the hypothesis that breast cancer patients carrying a sequence variant in
      the ATM gene differentially benefit from postoperative radiotherapy. These
      findings have to be verified using larger number of cases to clarify the clinical
      consequences of sequence variants in the ATM gene.

PMID- 15450732
TI  - Radiosensitivity is predicted by DNA end-binding complex density, but not by
      nuclear levels of band components.
AB  - BACKGROUND AND PURPOSE: We previously determined that the density of a rapidly
      migrating DNA end-binding complex (termed 'band-A') predicts radiosensitivity of
      human normal and tumor cells. The goal of this study was first to identify the
      protein components of band-A and to determine if the protein levels of band-A
      components would correlate with band-A density and radiosensitivity. PATIENTS AND
      METHODS: DNA end-binding protein complex (DNA-EBC) protein components were
      identified by adding antibodies specific for a variety of DNA repair-associated
      proteins to the DNA-EBC reaction and then noting which antibodies super-shifted
      various DNA-EBC bands. Band-A levels were correlated with SF2 for a panel of
      primary human fibroblasts heterozygous for sequence-proven mutations in BRCA1 or
      BRCA2. The nuclear protein levels of band-A components were determined in each
      BRCA1 heterozygote by western hybridization. RESULTS: DNA-EBC analysis of human
      nuclear proteins revealed 10 identifiable bands. The density of the most rapidly
      migrating DNA-EBC band correlated closely with both BRCA-mutation status and
      radiosensitivity (r(2)=0.85). This band was absent in cells with homozygous
      mutations in their ataxia-telangiectasia-mutated protein (ATM) genes. This band
      was also completely supershifted by the addition of antibodies to ATM, Ku70, DNA
      ligase III, Rpa32, Rpa14, DNA ligase IV, XRCC4, WRN, BLM, RAD51 and p53. However,
      the intranuclear concentrations of these proteins did not correlate with either
      the SF2 or DNA-EBC density. Neither BRCA1 or BRCA2 could be detected in band-A.
      CONCLUSIONS: DNA-EBC analysis of human nuclear extracts resulted in 10 bands, at
      least six of which contained ATM. The density of one of the DNA-EBCs predicted
      the radiosensitization caused by BRCA haploinsufficiency, and this band contains
      Ku70, ATM, DNA ligase III, Rpa32, Rpa14, DNA ligase IV, XRCC4, WRN, BLM, RAD51
      and p53 but not BRCA 1 or 2. The density of band-A was independent of the nuclear
      concentration of any of its known component.

PMID- 15450733
TI  - In vivo imaging of apoptosis by 99mTc-Annexin V scintigraphy: visual analysis in
      relation to treatment response.
AB  - BACKGROUND AND PURPOSE: Anticancer therapy induces apoptosis in a dose- and time
      dependent fashion. (99m)Tc-Hynic-rh-Annexin V scintigraphy (TAVS) enables non
      invasive in vivo imaging of treatment-induced apoptosis. We identified the visual
      patterns of (99m)Tc-Hynic-rh-Annexin V tumour uptake and related these to
      treatment response. PATIENTS AND METHODS: Thirty-three patients with malignant
      lymphoma (n=26), leukaemia (n=1) NSCLC (n=5), H&NSCC (n=1), scheduled for
      radiotherapy (n=27), platinum-based chemotherapy (n=5) or concurrent
      chemoradiation (n=1), underwent TAVS before and early after the start of
      treatment. Planar and SPECT images were visually examined to assess changes in
      tumour (99m)Tc-Hynic-rh-Annexin V uptake. Twenty-nine patients were eligible for
      further analysis. Annexin V uptake before (U(baseline)) and early after (U(post))
      the start of treatment was graded using a four-step scale: 0, absent; 1, weak; 2,
      moderate and 3, intense. The difference between these values (Delta U) was
      calculated and correlated to tumour response after therapy (Spearman rank
      correlation test). RESULTS: Weak to moderate U(baseline) was detected in 13/15
      patients with a complete response and U(post) was markedly increased in all these
      cases (Delta U range 1-3). Partial response (n=7) was associated with weak to
      moderate U(baseline) and a moderately increased U(post) (Delta U range 1-2). In
      patients with stable disease (n=5), U(baseline) was predominantly weak, without
      considerable changes in uptake after the start of treatment (Delta U range 0-1).
      Finally, in case of progressive disease (n=2), either no tumour uptake or a
      decrease in U(post) was detected (Delta U=-1). A statistically significant
      correlation was found between changes in (99m)Tc-Hynic-rh-Annexin V tumour uptake
      and clinical response (correlation coefficient=0.62; P<0.001). CONCLUSIONS:
      Complete or partial tumour response was associated with a marked increase of
      (99m)Tc Hynic-rh-Annexin V accumulation early during treatment compared to
      baseline values. In case of stable or progressive disease, pretreatment scans
      demonstrated predominantly low (99m)Tc Hynic-rh-Annexin V tumour uptake and no
      significant increase early after treatment. These results indicate that TAVS
      might be useful as a predictive test for treatment response.

PMID- 15450734
TI  - Recombinant adeno-associated virus 2-mediated transfer of the human superoxide
      dismutase gene does not confer radioresistance on HeLa cervical carcinoma cells.
AB  - BACKGROUND AND PURPOSE: The success rate of any therapeutic approach depends on
      the therapeutic window, which can be increased by either raising the resistance
      of the normal tissue without protecting the tumor cells or by sensitizing the
      tumor cells but not the normal cells. Two promising candidate genes for normal
      tissue protection against radiation-induced damage may be the copper-zinc
      (CuZnSOD) and manganese superoxide-dismutase genes (MnSOD). The recombinant adeno
      associated virus 2 (rAAV-2) offers attractive advantages over other vector
      systems: low immunogenicity, ability to infect dividing and non-dividing tissues
      and a low chance of insertional mutagenesis, due to extra-chromosomal
      localization. We report the production of novel rAAV-2-SOD vectors and the
      investigation of their modulating effects on HeLa-RC cells after irradiation.
      MATERIAL AND METHODS: rAAV-2 vectors were cloned containing the human CuZnSOD or
      MnSOD as transgene and vector stocks were produced. In the initial experiments
      human cervix carcinoma (HeLa-RC) cells were chosen for their susceptibility to
      rAAV-2. On day 0, cells were seeded and transduced with the rAAV-2-SOD vectors.
      On day 3, cells were harvested, irradiated (0.5-8 Gy) and reseeded in different
      assays (FACS, SOD, MTT and colony assays). RESULTS: Although >70% of all cells
      expressed SOD and significant amounts of functional SOD protein were detected, no
      radioprotective effect of SOD was observed after transduction of HeLa-RC cells.
      CONCLUSIONS: Novel rAAV-2-SOD vectors that could be produced at high titer, were
      able to efficiently infect cells and express the SOD genes. The absence of a
      radioprotective effect in HeLa-RC cancer cells indicates an additional safety
      feature and suggests that rAAV-mediated MnSOD overexpression might contribute to
      increasing the therapeutic index when applied for normal tissue protection.

PMID- 15450735
TI  - Optimisation and validation of methods to assess single nucleotide polymorphisms
      (SNPs) in archival histological material.
AB  - BACKGROUND AND PURPOSE: An increasing amount of evidence indicates that single
      nucleotide polymorphisms (SNPs) may affect a variety of oncology related
      phenotypes. Occasionally, it is convenient to base studies addressing genotype
      phenotype relationships on historical patient cohorts, from which only archival
      specimens are available. This study was conducted to validate protocols optimised
      for assessment of SNPs based on paraffin embedded, formalin fixed tissue samples.
      PATIENTS AND METHODS: In 137 breast cancer patients, three TGFB1 SNPs were
      assessed based on archival histological specimens. In 37 of these patients, the
      SNPs were also assessed using cultured fibroblasts and the assays were validated
      by direct comparison of the results. From the remaining 100 patients, only
      archival material was available. In these patients, the existence of a genetic
      linkage pattern between the assessed TGFB1 SNPs was used to provide an indirect
      validation of the genotyping results. Furthermore, two different methods for DNA
      extraction were compared (semi-automatic DNA extraction using the ABI Prism 6100
      Nucleic Acid PrepStation versus Proteinase K digestion for 5 days followed by
      boiling and DNA precipitation). RESULTS: Assessment of SNPs based on archival
      histological material is encumbered by a number of obstacles and pitfalls.
      However, these can be widely overcome by careful optimisation of the methods used
      for sample selection, DNA extraction and PCR. Within 130 samples that fulfil the
      criteria for analysis a highly reliable SNP assessment was observed. The study
      demonstrated that different 'down-stream applications' ('single nucleotide primer
      extension' or 'TaqMan-based' real-time PCR) could be used as genotyping
      procedure. CONCLUSIONS: Reliable assessment of SNPs in formalin-fixed paraffin
      embedded specimens is possible but a number of precautions should be carefully
      taken.

PMID- 15450736
TI  - Hope for a broken heart?
AB  - Heart failure affects 23 million people worldwide and results from cardiac
      dysfunction characterized by decreased responsiveness to beta-adrenergic
      stimulation. A recent publication by W.J. Koch and colleagues highlights evidence
      for targeted beta-adrenergic receptor kinase (betaARK1) inhibition by gene
      transfer to improve contractile function and beta-adrenergic responsiveness in
      failing human myocardium. This proof-of-concept study has great importance for
      future heart failure therapy because it provides evidence for the therapeutic
      effectiveness of betaARK1 inhibition in failing human myocardium.

PMID- 15450737
TI  - Tailor-made glycoproteins.
AB  - Posttranslational modifications are a fundamental mechanism for the regulation of
      cellular physiology and function. A recent paper by Zhang et al. provides a novel
      strategy for the generation of homogeneous glycoproteins. The ability to install
      covalent modifications site-specifically into proteins holds tremendous promise
      for deciphering the role of posttranslational modifications and has exciting
      implications for the development of protein therapeutics.

PMID- 15450738
TI  - An array of diverse microbial genomes.
AB  - Methods for comparing gene frequencies across large, epidemiologically defined
      bacterial collections are limited. A novel microarray technology has been
      developed called 'library on a slide'. In this technology, hundreds of entire
      microbial genomes are arrayed, rather than sequences of a single genome or sets
      of genes. These slides can then be probed for the presence of specific genes
      allowing researchers to draw inferences regarding important differences between
      related strains that differ in their pathogenic potential.

PMID- 15450739
TI  - Adult stem cells: capturing youth from a bulge?
AB  - With the development of advanced cell-labeling technologies, fluorescence
      activated cell sorting (FACS), as well as improved understanding of mammalian
      gene expression, it is now possible to identify and isolate specific sub
      populations of adult mammalian cells with good accuracy. Recent publications by
      Morris et al. and Tumbar et al. demonstrate the isolation of putative epithelial
      stem cells from the hair follicle bulge and Affymetrix expression arrays were
      employed to elucidate putative genes that might control stem cell fates.

PMID- 15450740
TI  - Genetically engineered phytoremediation: one man's trash is another man's
      transgene.
AB  - Plant-based environmental remediation, or phytoremediation, has been widely
      pursued in recent years as a favorable clean-up technology and is an area of
      intensive scientific investigation. For the vast majority of field applications,
      vegetative 'phyto-crops' are selected specifically for their capacity for site
      decontamination and not for additional concurrent or post-remediation utility. By
      contrast, a recent publication by Ellis and colleagues highlights potential anti
      carcinogenic uses for plants genetically engineered primarily for detoxification
      of selenium-polluted soils and sediments.

PMID- 15450741
TI  - Exploring the post-transcriptional RNA world with DNA microarrays.
AB  - Genomic approaches are valuable for understanding the complex layer of gene
      regulation that involves the control of RNA processing, localization and
      stability. Recent work provides a prime example of the power of unbiased
      microarray-based methods to discover unexpected functions for proteins in the RNA
      world. The challenges ahead relate to extending such approaches to larger genomes
      and to integrating this type of information with that generated by standard
      expression profiling.

PMID- 15450742
TI  - Sindbis virus--an effective targeted cancer therapeutic.
AB  - Viral therapies for cancer therapy have many potential positive attributes. These
      include the ability to specifically infect targeted cells, specifically express
      toxic or immune-enhancing genes, and the ability to specifically replicate within
      a tumor cell. Despite these biological advantages, efficacy to date has been
      limited. A recent report demonstrates that the Sindbis virus has remarkable
      properties in three challenging areas of gene therapy - specificity, efficacy and
      delivery, suggesting that Sindbis has the potential to become an important gene
      therapy vector for cancer therapy.

PMID- 15450743
TI  - Harnessing the developmental potential of nucellar cells: barriers and
      opportunities.
AB  - Angiosperm nucellar cells can either use or avoid meiosis in vivo, depending on
      the developmental context. This unique ability contrasts with the conditions
      required in vitro, either for a reconstituted oocyte to avoid meiosis and produce
      clones by somatic cell nuclear transfer (SCNT), or for mammalian stem cells to
      undergo meiosis and produce synthetic sex cells (gametes). Current
      biotechnological initiatives to harness the potential of nucellar cells are based
      on the transfer of apomixis genes to sexual crop plants with the aim of producing
      clones through seeds. The elusive genetic basis of apomixis compels us to examine
      whether this process involves epigenetic factors. The elegant and versatile
      developmental platform available in nucellar cells should be explored as a genome
      scale science and compared with mammalian stem cell biology for a holistic
      understanding of developmental programming and reprogramming in eukaryotes.

PMID- 15450744
TI  - Hydrophobic peptide tags as tools in bioseparation.
AB  - Hydrophobic interactions are highly selective, and differences in surface
      hydrophobicities between proteins can be used as an efficient handle to
      facilitate protein isolation. Aromatic amino acid residues are of particular
      importance for molecular recognition because they have a key role in several
      biological functions. The hydrophobicity of a protein can easily be altered with
      minor genetic modifications, such as site-directed mutagenesis or fusions of
      hydrophobic peptide tags. An important advantage of hydrophobic peptide tags over
      traditional affinity tags is the possibility of exploring simple and inexpensive
      bioseparation materials. Recent results demonstrate the potential of hydrophobic
      interaction chromatography and aqueous two-phase systems as tools to study
      relative hydrophobicities of recombinant proteins with only minor alterations.
      This review focuses on hydrophobic peptide tags as fusion partners, which can be
      used as important tools in bioseparation.

PMID- 15450745
TI  - Biomedicines to reduce inflammation but not viral load in chronic HCV--what's the
      sense?
AB  - Although cytokines and cytotoxic T lymphocytes (CTL) are among the predominant
      mechanisms of host defense against viral pathogens, they can induce an
      inflammatory response that often leads to tissue injury. Hepatitis C virus (HCV)
      infection, a major cause of liver-related disease, results in the induction of
      proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha), and
      CTL activity, followed by liver injury. Although inflammation facilitates the
      wound healing process, chronic persistence over several decades results in scar
      accumulation, fibrosis and often cirrhosis. This review summarizes biological
      data implicating a cause-and-effect relationship between TNF-alpha levels and the
      progression of fibrosis in chronic HCV infections, in contrast to the role of TNF
      alpha in hepatitis B virus infections. Furthermore, an overview of therapeutic
      approaches to halting the inflammatory cascade in individuals with chronic HCV,
      including the use of agents to reduce the level of TNF-alpha, is presented.

PMID- 15450746
TI  - Sugar-mediated ligand-receptor interactions in the immune system.
AB  - Most molecules involved in the recognition and elimination of pathogens by the
      immune system are glycoproteins. Oligosaccharides attached to glycoproteins
      initiate biological functions through mechanisms that involve multiple
      interactions of the monosaccharide residues with receptors. For example,
      calreticulin, a quality-control lectin-like chaperone, interacts with
      glucosylated mannose glycans presented by empty major histocompatibility complex
      (MHC) class I molecules, retaining them in the endoplasmic reticulum (ER) until
      antigenic peptide is loaded. Clusters of specific IgG glycoforms, present in
      increased amounts in rheumatoid arthritis, bind mannose-binding lectin (MBL),
      providing a potential route to inflammation through activation of the complement
      pathway. Secretory IgA glycans bind gut bacteria, and an unusual cluster of
      mannose residues on gp120, the surface coat protein of the HIV virus, is
      recognized by the novel 'domain-swapped' IgG 2G12 serum antibody.

PMID- 15450747
TI  - Glucose and sucrose: hazardous fast-food for industrial yeast?
AB  - Yeast cells often encounter a mixture of different carbohydrates in industrial
      processes. However, glucose and sucrose are always consumed first. The presence
      of these sugars causes repression of gluconeogenesis, the glyoxylate cycle,
      respiration and the uptake of less-preferred carbohydrates. Glucose and sucrose
      also trigger unexpected, hormone-like effects, including the activation of
      cellular growth, the mobilization of storage compounds and the diminution of
      cellular stress resistance. In an industrial context, these effects lead to
      several yeast-related problems, such as slow or incomplete fermentation, 'off
      flavors' and poor maintenance of yeast vitality. Recent studies indicate that the
      use of mutants with altered responses to carbohydrates can significantly increase
      productivity. Alternatively, avoiding unnecessary exposure to glucose and sucrose
      could also improve the performance of industrial yeasts.

PMID- 15450748
TI  - High-throughput cell-free systems for synthesis of functionally active proteins.
AB  - Continuous cell-free translation systems with perpetual supply of consumable
      substrates and removal of reaction products made the process of in vitro
      synthesis of individual proteins sustainable and productive. Improvements of cell
      free reaction mixtures, including new ways for efficient energy generation, had
      an additional impact on progress in cell-free protein synthesis technology. The
      requirement for gene-product identification in genomic studies, the development
      of high-throughput structural proteomics, the need for protein engineering
      without cell constraints (including the use of unnatural amino acids), and the
      need to produce cytotoxic, poorly expressed and unstable proteins have caused
      increased interest in cell-free protein synthesis technologies for molecular
      biologists, biotechnologists and pharmacologists.

PMID- 15450749
TI  - Molecular cloning of the seventh component of complement in rainbow trout.
AB  - C7 is an integral component of the lytic pathway of complement, which interacts
      in a sequence of polymerization reactions with other terminal components to form
      the membrane attack complex. C7 plays a central role in the terminal complement
      cascade, since its incorporation into the nascent complex allows its hydrophilic
      amphiphilic transition, which subsequently leads to the direct binding of the
      complex to the target membrane. To date, only human and porcine C7 have been
      cloned and characterized. Here we report the isolation of a C7 molecule from the
      rainbow trout (Oncorhynchus mykiss). The full-length trout C7 cDNA was isolated,
      and the predicted amino acid sequence exhibits 44 and 65% identity with human and
      Japanese flounder C7, respectively. The cysteine backbone and two putative N
      linked glycosylation sites are conserved in trout C7. It also contains the same
      structural motifs as those found in mammalian C7. Trout C7 mRNA expression was
      detected in all tissues investigated, except kidney and spleen.

PMID- 15450750
TI  - Differential gene expression profile in hepatopancreas of WSSV-resistant shrimp
      (Penaeus japonicus) by suppression subtractive hybridization.
AB  - In order to find the immune-relevant factors responsible for the virus resistance
      in the WSSV-resistant shrimp, a suppression subtractive hybridization method was
      employed to identify differentially expressed genes and their expression profile
      in the hepatopancreas of the virus-resistant penaeid shrimp. Thirty five genes
      were identified from more than 400 clones, of which eight are found for the first
      time in penaeid shrimp. betaGBP is the most abundant gene in our subtractive
      library except hemocyanin. Lectin, ferritin, oxygenase and chitinase of the virus
      resistant shrimp all showed up-regulation in expression compared with those of
      normal shrimp. In addition, Ranbp, Rho and Rab were found in the subtractive
      library. This is the first evidence indicating that small GTPases are involved in
      the signal transduction in shrimp defense response. Furthermore, a number of
      genes encoding apoptotic-related proteins and antioxidant enzymes were expressed
      at a higher level in the virus-resistant shrimp. In short, the high expression of
      immuno-related genes in response to the virus infection and the involvement of
      small GTPases in the antiviral response provide a new insight for further study
      in the crustacean innate immunity.

PMID- 15450751
TI  - Participation of serum and membrane lectins on the oxidative burst regulation in
      Macrobrachium rosenbergii hemocytes.
AB  - Using a spectrophotometric NBT reduction assay and phagocytosis, we identified
      that production of superoxide anions and phagocytic activity of hemocytes from
      Macrobrachium rosenbergii were significantly higher in the presence of rat,
      rabbit, and chicken erythrocytes than with human, pig, or horse erythrocytes.
      Hemocytes stimulated with MrL, MrLMab, or PMA increased 4.7, 5.1, and 6.1 fold,
      respectively, the oxidative response as compared to non-stimulated hemocytes.
      MrLMab together with MrL increased 5.7 fold the oxidative capacity of hemocytes
      as compared to non-stimulated cells. These effects were inhibited with 100 mM
      GalNAc, GlcNAc, or Neu5Ac and 0.2 microM of sialylated submaxillary gland mucin
      and fetuin. Piroxicam inhibited (P < 0.05) the production of O(2)(-) induced by
      MrL, whereas iodoacetamide inhibited the effect of MrLMAb (P < 0.05) in a dose
      dependent manner. Our results suggest that MrLMab might activate the oxidative
      burst through the metabolism of glucose as opposed to MrL which utilizes NADPH
      independent mechanisms, very probably through pro-inflammatory metabolites.

PMID- 15450752
TI  - Molecular characterization of the Japanese flounder, Paralichthys olivaceus,
      CD3epsilon and evolution of the CD3 cluster.
AB  - A second CD3 gene, i.e. CD3epsilon, has been cloned and sequenced in Japanese
      flounder. The full length cDNA is 1006 bp and encodes 164 amino acids. When
      compared with other known CD3epsilon peptide sequences, the most conserved region
      of the Japanese flounder CD3epsilon chain peptide is the cytoplasmic domain and
      the least conserved is the extracellular domain. A phylogenetic analysis based on
      the deduced amino acid sequence grouped the two Japanese flounder CD3 sequences
      with CD3epsilon and CD3gamma(delta, respectively. The Japanese flounder
      CD3epsilon gene has Lyf-1, GATAs, Oct-1, CEBPs, AP-1, and NF-AT but lacks TATA
      and CCAAT elements in the 5' flanking region. The Japanese flounder CD3 cluster
      (consisting of CD3epsilon and CD3gamma(delta) spans only 10.4 kb. The two genes
      are oppositely transcribed only 3.8 kb apart. Both Japanese flounder CD3 genes
      have five exons. The two Japanese flounder CD3 genes were predominantly expressed
      in PBLs, kidney, spleen, and gills. A polyclonal rabbit antiserum that reacts
      with the CD3 marker on human T cells also reacted with Japanese flounder
      CD3epsilon. The epitope highly conserved between mammalian and non-mammalian
      CD3epsilons, this antibody bound to a single 15 kDa peptide.

PMID- 15450753
TI  - Analysis of a catfish gene resembling interleukin-8: cDNA cloning, gene
      structure, and expression after infection with Edwardsiella ictaluri.
AB  - Chemokines are important mediators for innate immunity involved in recruitment,
      activation and adhesion of a variety of leukocyte types to inflammatory foci.
      While almost all chemokines have been identified from mammals, only a handful of
      fish chemokines have been identified. Here we report molecular cloning, sequence
      analysis, and expression of a channel catfish gene resembling interleukin-8 (IL
      8). The gene has two alternatively spliced transcripts encoding 114 and 111 amino
      acids, respectively. The gene has four exons and three introns, typical of the
      CXC chemokine gene organization. In spite of the structural conservation through
      evolution, the piscine IL-8 genes showed a much greater sequence divergence than
      their counterparts among mammals. RT-PCR indicated that both spliced forms were
      expressed. Expression of the IL-8 like gene was up-regulated 3-5-fold in channel
      catfish and blue catfish after infection with pathogenic bacteria Edwardsiella
      ictaluri.

PMID- 15450754
TI  - Cloning and characterization of chicken stromal cell derived factor-1.
AB  - Stromal cell derived factor-1, SDF-1, belongs to the CXC family of chemokines and
      has been identified in mammals, amphibians, and fish. This chemokine has a
      diverse array of functions in organogenesis, hematopoeisis, B cell development
      and recruitment of immune system cells. Here, we report the cloning of the
      chicken SDF-1 ortholog and examine its temporal and spatial expression. The
      chicken SDF-1 cDNA contained an open reading frame encoding a predicted protein
      of 89 amino acids, which shared 40-75% identity to SDF-1 protein in other
      species. Protein folding simulation predicted a tertiary structure very similar
      to that obtained for human SDF-1. Recombinant chicken SDF-1 was produced using a
      prokaryotic expression system and the recombinant protein was shown to be
      biologically active in a calcium flux assay. The SDF-1 gene was found to be
      expressed ubiquitously and constitutively in adult tissues and was present as
      early as the primitive streak stage of chicken embryos.

PMID- 15450755
TI  - Specific antibody secreting cells from chickens can be detected by three days and
      memory B cells by three weeks post-infection with the avian respiratory
      coronavirus.
AB  - Infectious bronchitis virus (IBV), the first coronavirus described, has been a
      continuing problem in poultry for more than 70 years. IBV, causing a highly
      contagious respiratory disease in chickens, resembles the recently described
      severe acute respiratory syndrome virus in pathogenesis and genome organization.
      While previous studies demonstrated that effector and memory CD8(+) T lymphocytes
      are critical in controlling acute IBV infection and disease in chickens, here
      chicken anti-IBV antibody (IgG) secreting cells (ASC) in both peripheral blood
      mononuclear cells (PBMC) and spleens collected following IBV Gray infection were
      evaluated using an ELISPOT assay. The ASC in peripheral blood and spleens can be
      detected from 3 to 7 days post-infection (p.i.), which is 3-7 days earlier than
      anti-IBV IgG detected in the serum. The ASC frequency reached a maximum at 7-10
      days p.i., and decreased more than 90% in the spleen and 70% in PBMC by 14 days
      p.i. The ASC levels in the PBMC then decreased gradually to 0.5 ASC/10(6) over
      the next 8 weeks. The higher concentration of about 20 ASC/10(6) cells in spleens
      may, at least partially, account for the presence of antibody in the serum
      although bone marrow ASC were not determined. In vitro stimulation of PBMC and
      splenocytes with IBV antigen demonstrated that memory B cells can be activated to
      secrete antibody by 3 weeks p.i. ELISPOT detection of primary B cells could be
      useful in the early detection of infection following infection with respiratory
      coronaviruses.

PMID- 15450756
TI  - Evaluation of the antibody mediated immune response in nestling American kestrels
      (Falco sparverius).
AB  - Avian biologists and toxicologists use tests of immune function to evaluate
      health or quality in birds. Nestlings are widely studied members of the
      population because of the logistical ease of working with them, and because of
      their vulnerability to environmental contaminants. Current immunological
      techniques are designed for domestic poultry and are far from ideal, since
      poultry are precocial (developmentally mature at hatching), while many wild
      species are altricial (developmentally immature, i.e. blind, naked and totally
      dependent at hatching). The purpose of this study was to identify a sensitive
      means of evaluating in vivo antibody responsiveness in nestling American
      kestrels. Two antigens, sheep red blood cells (SRBC), and dinitrophenol-keyhole
      limpet hemocyanin (DNP-KLH), were used to stimulate a B cell mediated response.
      Antibody production was measured using a hemagglutination assay (SRBC), or an
      enzyme-linked immunosorbent assay (DNP-KLH). Two formulations of the antigen DNP
      KLH were compared. DNP-KLH stimulated a stronger and more consistent antibody
      response in nestling kestrels than did SRBCs.

PMID- 15450757
TI  - Prenatal HgCl2 exposure in BALB/c mice: gender-specific effects on the ontogeny
      of the immune system.
AB  - Because mercury is highly toxic to developing organisms, we tested the hypothesis
      that prenatal exposure to HgCl(2) can induce persistent immune dysfunction.
      Pregnant BALB/c mice were administrated every other day, for 11 days with HgCl(2)
      (200 microg/kg). Their offspring were studied at PND10, 14, 21, and 60. Lymph
      nodes (LN), spleens, and thymus were harvested and proliferation and cytokine
      production were studied in vitro. We report that prenatal HgCl(2) exposure exerts
      organ-specific effects on cell number, proliferation, and cytokine production in
      pre-weaning pups. At adulthood (PND60), effects of prenatal HgCl(2) exposure were
      still observed, but expressed differently in females and males. In adult females,
      an inhibitory effect was observed on cytokine production by thymocytes, LN cells,
      and splenocytes. In males, a stimulatory effect was observed. Overall, we
      conclude that in vivo exposures to low doses of HgCl(2) can induce persistent sex
      specific immunotoxic effects, observable in adulthood.

PMID- 15450758
TI  - Understanding the plight of foster youth and improving their educational
      opportunities.

PMID- 15450759
TI  - Disciplinary choices of mothers of deaf children and mothers of normally hearing
      children.
AB  - OBJECTIVE: To assess the disciplinary preferences of mothers of profoundly deaf
      children and normally hearing children in a test of the hypothesized link between
      child disabilities and punitive parenting. METHOD: Disciplinary preferences of
      mothers seeking a cochlear implant for their profoundly deaf child (n=57),
      mothers not seeking an implant for their deaf child (n=22), and mothers of
      normally hearing children (n=27) were assessed using an analog task in which
      subjects select discipline in response to slide images of children engaging in
      normative or frankly deviant behaviors that are potentially irritating. RESULTS:
      Results indicated that mothers of children with profound hearing impairments were
      more likely to select physical discipline in response to depicted child
      transgressions and more likely to escalate to physical discipline when the
      depicted child was described as persisting in the transgression. Additionally,
      escalation was more probable in response to scenes depicting children engaged in
      dangerous and destructive acts than in rule-violating acts. CONCLUSIONS: Findings
      were consistent with the hypothesized link between childhood disabilities and
      child maltreatment as well as the hypothesis that children with disabilities
      associated with communication problems could be at risk of physical abuse.

PMID- 15450760
TI  - Telling their stories: primary care practitioners' experience evaluating and
      reporting injuries caused by child abuse.
AB  - OBJECTIVE: To learn about primary care physicians' experiences in identifying and
      reporting injuries caused by physical abuse. METHOD: Two qualitative analysts
      facilitated a focus group of six Chicago area, primary care physicians.
      Physicians representing diverse practice settings were selected to participate in
      the discussion. The analysts reviewed and analyzed the audiotape transcription of
      the focus group for common emergent themes. RESULTS: Two themes emerged: (1) the
      importance of the participants' own past experience identifying and reporting
      suspected child abuse and (2) the responsibility physicians experience as they
      strive to assess possible abuse within the time constraints of an office visit.
      Each physician described a sentinel event that continues to affect decision
      making. The physicians described several obstacles to decision-making including a
      lack of knowledge about child abuse, their previous experience with child
      protective services (CPS), and the additional time required to evaluate and
      report suspected abuse. The discussion suggested that rapid availability of
      expert consultation improved participant comfort in decision-making when abuse or
      neglect is suspected. CONCLUSION: Primary care physicians reported being strongly
      influenced by their previous experiences with suspected abuse. A better
      understanding of office-based experiences with suspected abuse is needed to guide
      the development of tools and systems to enhance the ability of the primary care
      physician to provide the best care for children who may have been abused.

PMID- 15450761
TI  - An event history analysis of recurrent child maltreatment reports in Florida.
AB  - OBJECTIVE: The purpose of this study was to (a) describe the timing of
      maltreatment recurrence and (b) measure associations between child demographics
      and characteristics of initial reports with recurrent maltreatment. METHOD: Using
      administrative data from the Florida Department of Children and Families, case
      histories of 189,375 children with an initial maltreatment report in 1998 or 1999
      were examined using event history techniques, also known as survival analysis, to
      assess the relationship between predictor variables and the likelihood and timing
      of recurrence. Specifically, data were analyzed using descriptive and
      multivariate analytic methods, including life-table analysis and logistic
      regression analysis. RESULTS: Over 26% of the sample had a maltreatment
      recurrence during the 2-year follow-up period, and the risk of recurrence was
      greatest in the first 4 months after the initial incident. Results also suggest
      the presence of unique associations between recurrence and a child's
      race/ethnicity and age, as well as indication level, maltreatment type, and
      service disposition as specified in the initial report. CONCLUSIONS: Results
      indicate that recurrent reports are more likely for young and White children
      whose first report resulted in a substantiation of neglect and the provision of
      in-home preventive services. This research highlights the importance of further
      investigating the relationship between chronic maltreatment and other influential
      variables.

PMID- 15450762
TI  - Measuring child maltreatment risk in communities: a life table approach.
AB  - OBJECTIVE: The purpose of this article is to: (1) illustrate the application of
      life table methodology to child abuse and neglect report data and (2) demonstrate
      the use of indicators derived from the life tables for monitoring the risk of
      child maltreatment within a community. METHOD: Computerized records of child
      maltreatment reports from a large, urban county in Ohio are cumulated for 11
      years and linked for each child. Life table methods are used to estimate the
      probability that children from birth to age 10 will be reported victims of
      maltreatment by age, race, and urban or suburban residence. RESULTS: Using life
      tables, the estimates in the county of this study are that 33.4% of African
      American children and 11.8% of White children will appear in substantiated or
      indicated child abuse or neglect report(s) by their 10th birthday. The age
      specific probability of a maltreatment report is highest in the first year of
      life for both groups. The probability of a child being reported for a
      substantiated or indicated incident of maltreatment before his or her 10th
      birthday is more than three times higher for city dwellers than for suburbanites
      in the urban county studied here. CONCLUSIONS: Life table methodology is useful
      for creating child well-being indicators for communities. Such indicators reveal
      that a larger portion of the child population is affected by maltreatment reports
      than would be concluded from examining cross-sectional rates and can be used to
      identify racial or geographic disparities.

PMID- 15450763
TI  - The effect of personal characteristics on reporting child maltreatment.
AB  - OBJECTIVE: This study examined the relationship between personal characteristics
      of 276 potential entry-level social service workers and their decision to report
      child maltreatment to Child Protective Services (CPS). The personal
      characteristics of interest were: age, gender, parenthood, mother's education,
      father's education, college major, ethnicity, and immigrant status. The study
      hypotheses were that personal characteristics would have: (1) an individual
      effect on reporting, (2) a combined effect on reporting, and (3) an effect on
      reporting beyond any effect mediated by approval of corporal punishment and
      perceptions of maltreatment. METHOD: Data were collected by a self-report survey
      employing vignettes in multi-item scales. Respondents rated (1) their approval of
      corporal punishment, (2) the seriousness of incidents of probable maltreatment,
      and (3) their likelihood of reporting incidents of probable maltreatment to CPS.
      RESULTS: Of the eight personal characteristics, only ethnicity and immigrant
      status had significant effects on reporting. Together with approval of corporal
      punishment and perception of maltreatment, ethnicity and immigrant status
      accounted for 32% of the variance in reporting (p <.001). CONCLUSION:
      Independently and combined, ethnicity and immigrant status have considerable
      effect on reporting behavior. Findings suggest that human service agencies should
      address issues of diversity and establish clear criteria for responding to child
      maltreatment.

PMID- 15450764
TI  - Perihematoma brain metabolism and edema: thus far, an elusive piece of a complex
      puzzle.

PMID- 15450765
TI  - HIV-associated dementia, Alzheimer's disease, multiple sclerosis, and
      schizophrenia: gene expression review.
AB  - RNA and protein gene expression technologies are revolutionizing our view and
      understanding of human diseases and enable us to analyze the concurrent
      expression patterns of large numbers of genes. These new technologies allow
      simultaneous study of thousands of genes and their changes in regulation and
      modulation patterns in relation to disease state, time, and tissue specificity.
      This review summarizes the application of this modern technology to four common
      neurological and psychiatric disorders: HIV-1-associated dementia, Alzheimer's
      disease, multiple sclerosis, and schizophrenia and is a first comparison of these
      diseases using this approach.

PMID- 15450766
TI  - Effect of mannitol on regional cerebral blood flow in patients with intracerebral
      hemorrhage.
AB  - AIM: To evaluate the regional cerebral blood flow (rCBF) changes following IV
      mannitol bolus in patients with intracerebral hemorrhage (ICH). METHODS: In a
      hospital based randomized placebo controlled study, 21 CT proven ICH patients
      with Glasgow coma scale (GCS) score of 5 or more were subjected to clinical
      evaluation including GCS and Canadian Neurological stroke (CNS) scale. Cranial
      SPECT study was undertaken before and 60 min after 20% mannitol 100 ml IV in 20
      min or sham infusion. The SPECT images were semi-quantitatively analyzed and
      asymmetry index of basal ganglia, frontal, parietal and occipital regions were
      calculated. RESULTS: There were 12 patients in mannitol and nine in control group
      who were evenly matched for age, mean arterial blood pressure, GCS score and size
      of hematoma. Only one patient died in mannitol group. Following mannitol, GCS
      score improved in six, worsened in two and remained unaltered in four patients.
      In the control group, GCS improved in seven, worsened in none and was unchanged
      in two patients. SPECT studies revealed reduction in asymmetry index in basal
      ganglia in four, frontal region in six, parietal in four and occipital region in
      five patients in mannitol group. In control group, asymmetry index was reduced in
      basal ganglia in one, frontal and parietal region in three each and occipital
      region in five patients. These differences between control and study group were
      not significant. CONCLUSION: Mannitol does not seem to significantly change the
      regional cerebral blood flow (rCBF) in ICH patients as evaluated by SPECT study.

PMID- 15450767
TI  - Cerebrospinal fluid isoprostanes are not related to inflammatory activity in
      relapsing-remitting multiple sclerosis.
AB  - Oxidative stress leads to lipid peroxidation and may contribute to the
      pathogenesis of lesions in multiple sclerosis (MS), an autoimmune disease
      characterised by inflammatory as well as degenerative phenomena. We previously
      found that cerebrospinal fluid (CSF) levels of isoprostane 8-epi-PGF2alpha, a
      marker of free radical damage and lipid peroxidation in vivo, were elevated in MS
      patients. Such levels were correlated with the degree of disability and reduced
      in subjects under steroid therapy. Here we investigated weather the CSF
      isoprostane levels correlated with disease inflammatory activity. To this aim, we
      enrolled 41 relapsing-remitting (RR) MS patients who underwent at the same time
      full neurological examination, NMR-imaging brain scan and diagnostic CSF test. No
      evidence of correlation was found between 8-epi-PGF2alpha levels and the presence
      of gadolinium (Gd)-enhancing NMR lesions or the time elapsed since the last
      relapse. We suggest that isoprostanes are not useful as surrogate inflammatory
      markers in MS. However, they may represent a sensitive index of degenerative
      phenomena, which can persist also in the absence of inflammatory activity.

PMID- 15450768
TI  - Cyclosporin A in treatment of refractory patients with chronic inflammatory
      demyelinating polyradiculoneuropathy.
AB  - To investigate the therapeutic efficacy of cyclosporin A (CyA) in the treatment
      of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), a
      microemulsion form of this drug (Neoral) was orally given to seven patients with
      the disease who were unresponsive or resistant to conventional therapies. The
      daily dose of CyA was carefully controlled in order to keep the plasma trough
      concentration between 100 and 150 ng/ml. Within 1 month of initiation of CyA, all
      patients subjectively showed improvement of clinical symptoms, while both
      modified Rankin and INCAT disability scores were significantly decreased (p <
      0.05) and grip strength was significantly increased (p < 0.05) 3 months after
      initiation compared with before. Total protein in the cerebrospinal fluid was
      significantly decreased 3 and 6 months after starting CyA (p < 0.05). Although
      the maximal motor nerve conduction velocity showed a significant improvement in
      the median nerve 1 to 1.5 years after commencement of CyA (p < 0.05), there were
      no significant changes in any other neurophysiological parameters. One patient
      with anti-sulphoglucuronyl paragloboside IgM antibodies gradually became
      resistant to CyA, but the rest have since been in good neurological condition
      without complications ascribable to this drug. These results suggest that oral
      CyA may be effective even for refractory cases with CIDP. CyA should be actively
      considered as a therapeutic option when patients with CIDP are resistant to
      conventional treatment.

PMID- 15450769
TI  - Correlates of quality of life after stroke.
AB  - The relationship between lesion location and quality of life (QOL) in stroke
      patients has not yet been clearly revealed. The present study was undertaken to
      investigate the clinical and anatomical correlates which can predict future QOL
      in stroke patients. The study subjects consisted of 69 consecutive patients with
      ischemic stroke who were followed up 2 months after the stroke event at the
      stroke unit. Quality of life was evaluated during the 2-month follow up period
      after the stroke. Baseline information or data including clinical and anatomical
      correlates (Beck Depression Inventory, Beck Anxiety Inventory, Barthel's Index,
      MRI data) at the time of the stroke event were collected by performing a review
      of each patient's chart and research data files. Severe subcortical gray matter
      lesion and depressive symptoms in the acute phase of stroke were of importance in
      predicting low QOL 2 months after stroke.

PMID- 15450770
TI  - Treatment and outcome of myasthenia gravis: retrospective multi-center analysis
      of 470 Japanese patients, 1999-2000.
AB  - To clarify the current status of treatments and outcomes of patients with
      myasthenia gravis (MG) in Japan, a total of 470 patients (164 men and 306 women;
      mean age 41 years) were recruited from 19 Japanese tertiary medical centers in
      1999-2000. Thymectomy was performed in 319 (68%) of the patients. Patients who
      received thymectomy were younger (p = 0.01) and had more severe disabilities (p <
      0.01) than patients without thymectomy. Irrespective of receiving thymectomy,
      most of the patients were administered corticosteroids (64%), other
      immunosuppressive agents (10%), or cholinesterase inhibitors (86%). Of 395
      patients followed up for more than 12 months after treatment (mean 8.0 years),
      30% (34% of thymectomized and 21% of non-thymectomized patients) were in
      remission (no symptoms with/without medication), 34% had only ocular symptoms,
      and the remaining 35% still had weakness of bulbar or limb muscles at the end of
      follow-up. The prognosis of MG in Japan was generally favorable, but despite the
      frequent use of thymectomy and immunosuppressive treatments, approximately one
      third of patients still had generalized weakness. More effective or intensive
      treatments are required to improve the prognosis.

PMID- 15450771
TI  - Recurrence and survival after first-ever stroke in the area of Bajo Aragon,
      Spain. A prospective cohort study.
AB  - OBJECTIVE: There have been no prospective studies in Spain focused on stroke
      recurrence. The purpose of this work is to estimate the risk of stroke recurrence
      and mortality in the community of Bajo Aragon, Spain and to compare it with
      previous studies conducted in other countries. METHODS: A cohort of 425 patients
      with first ever stroke was followed-up for a mean period of 4 years (range: 20-78
      months). The mean age was 75.4 years. The survival function for recurrence and
      mortality was analysed by means of the actuarial method. Survival comparisons
      were made for the different vascular risk factors with the Kaplan-Meier method.
      The risk of recurrence and death was adjusted for relevant variables with the Cox
      proportional hazards model. We also made a separate analysis by stroke subtypes.
      RESULTS: At the end of the follow-up we found an overall mortality of 38%
      (163/425) with 69 patients dying in hospital, and an overall recurrence rate of
      17.6% (63/356). The cumulative risk of recurrence was 2.1% at 30 days, 9.5% at 1
      year and 26% at 5 years. The cumulative risk of mortality was 16% at 30 days, 30%
      at 1 year and 48% at 5 years. Only age (Hazard Ratio: 1.05, 95% CI: 1.02-1.08)
      and the addition of risk factors (Hazard Ratio: 1.32, 95% CI: 1.12-1.57) were
      significant predictors of recurrence. In general, none of the risk factors
      individually predicted stroke recurrence. The highest risk of recurrence was
      observed in large-vessel atherothrombotic infarction followed by cardioembolic
      infarction. In cardioembolic stroke, the association of atrial fibrillation plus
      either valvular disease or congestive heart failure significantly predicted
      recurrence of the same type (Relative Risk: 3.1; 95% CI: 2.2-4.4). CONCLUSION:
      The risk of early stroke recurrence in our area was lower than those observed in
      most studies, so was the risk of long-term mortality. However, the risk of long
      term recurrence was similar. Age was the main predictor of death and recurrence.
      The patients with atrial fibrillation plus another heart disease are at increased
      risk of recurrent cardioembolic stroke.

PMID- 15450772
TI  - MRI evaluation of treatment of embolic stroke in rat with intra-arterial and
      intravenous rt-PA.
AB  - Using magnetic resonance imaging (MRI), we investigated treatment of a rat model
      of embolic stroke with rt-PA via intra-arterial (IA) and intravenous (IV) routes
      of administration. Rats were treated with rt-PA by either IA (n = 13) or IV (n =
      13) routes at 3 h after stroke induction. Diffusion, perfusion, T2, and
      magnetization transfer MRI were performed prior to and at 1-3 and at 24 h after
      embolization. The IA treated group exhibited smaller lesion volumes than the IV
      treated group (p = 0.02). The relative areas with low ADCW and cerebral blood
      flow (CBF) after IA rt-PA intervention were significantly (p < or = 0.03) smaller
      than those in the IV treated group at 24 h after embolization. Significant
      differences (p < 0.02) between IA and IV treated groups in the relative area with
      high T2 and inverse of the apparent forward transfer rate of magnetization (kINV)
      in the ipsilateral hemisphere were also detected at 24 h after embolization. The
      IA treated group exhibited less intracerebral hemorrhage (27%) than the IV
      treated (64%) groups. Our data suggest that the beneficial effects of IA rt-PA
      treatment can be detected by changes in CBF, ADCW, T2, and kINV.

PMID- 15450773
TI  - Preliminary studies of cytokine secretion patterns associated with pregnancy in
      MS patients.
AB  - Multiple sclerosis has a tendency to remit during pregnancy, followed by an
      increase in the risk for disease relapses in the postpartum period. In this
      communication, preliminary data are presented to indicate that activated
      peripheral blood mononuclear cells (PBMC) from the postpartum period secrete
      elevated levels of gamma-interferon (IFN-gamma) relative to those collected
      during the third trimester. In addition, myelin antigen-specific T cell lines
      established from the third trimester of pregnancy secrete elevated levels of
      interleukin-10. The data suggest that the study of the mechanisms underlying
      natural fluctuations in disease activity during pregnancy and the postpartum
      period holds promise for a better understanding of factors capable of initiating
      and regulating remission and exacerbation in MS.

PMID- 15450774
TI  - Selection of recombinant phages binding to pathological endothelial and tumor
      cells of rat glioblastoma by in-vivo display.
AB  - Pathological endothelial cells are attractive targets to selectively abrogate
      tumor growth. However, only a few cell surface molecules to address the
      endothelium of pathological blood vessels are known, but it could be anticipated
      that many more molecular addresses associated with abnormal endothelial function
      and proliferation could serve as potential candidates for development of drug
      delivery agents. To obtain a library of peptides mediating binding of recombinant
      M13 phages to endothelium of experimental rat brain tumors, in-vivo display of a
      combinatorial heptapeptide and a splenocyte M13 library was used. Phage clones
      were selected that bind to rat brain tumor endothelium in-vivo and phage proteins
      detected in tissues by immunohistochemistry. Some of the recombinant phages
      diffused or were transported far into the surrounding tumor tissue, where they
      persisted for several days. Sequence analysis of insertion peptides revealed
      surprising similarities to angiogenic and anti-angiogenic factors or matrix and
      guidance molecules that appear to be involved in glioblastoma pathology. In-vivo
      phage display of recombinant M13 phages is a tool to select peptides targeting
      pathological endothelium. Insertion peptides, their corresponding cellular
      proteins and ligands might have a variety of applications in providing molecular
      tools for targeting tumor vascular beds with diagnostic probes and therapeutic
      substances and might open new opportunities for treating frequently fatal glial
      tumors.

PMID- 15450775
TI  - A case of complicated spastic paraplegia 2 due to a point mutation in the
      proteolipid protein 1 gene.
AB  - Pelizaeus-Merzbacher disease (PMD) is a rare X-linked dysmyelinating disorder
      resulting from mutation of the proteolipid protein gene (PLP1). Clinical features
      of PMD include progressive psychomotor developmental delay, nystagmus, spastic
      quadriplegia, dystonia, and cerebellar ataxia. PMD is clinically classified into
      three subtypes according to the severity of the disease: connatal, transitional,
      and classic forms. Patients with PMD have been identified with duplication, point
      mutations, and deletion of PLP1. In addition, spastic paraplegia 2 (SPG2) is
      allelic to PMD and typically caused by missense mutations in the second
      extracellular domain of PLP1 or in the PLP1-specific region that is spliced out
      during formation of the DM20 isoform. The authors describe a Korean boy diagnosed
      with SPG2 caused by a mutation that results in a Pro215Leu substitution in the
      second extracellular domain. Analysis of phenotypes resulting from mutations
      affecting PLP1 has been valuable in identifying functional domains of this still
      incompletely understood major myelin protein. Null mutations and mutations
      affecting the PLP1-specific domain cause peripheral neuropathy. The PLP1-specific
      domain also is important in the long-term maintenance of axonal integrity. This
      patient's phenotype was relatively mild, in contrast with other mutations at
      position 215 of PLP1 that cause severe PMD. One of these severe mutations is also
      a missense mutation substituting an aliphatic residue, alanine, for proline. The
      distinct severity difference between the Pro215Leu and Pro215Ala substitutions
      suggests that this region of the protein is very sensitive to subtle structural
      changes and likely plays a critical role in PLP1 function.

PMID- 15450776
TI  - Infarcts presenting with a combination of medial medullary and posterior inferior
      cerebellar artery syndromes.
AB  - Cerebellar and medial medullary infarctions are well-known vertebrobasilar stroke
      syndromes. However, their development in a patient with distal vertebral artery
      occlusion has not been previously reported. A 49-year-old man with longstanding
      hypertension suddenly developed vertigo, right-sided Horner syndrome, and left
      sided weakness. An MRI of the brain showed acute infarcts in the right inferior
      cerebellum (posterior inferior cerebellar artery territory) and the right upper
      medial medulla (direct penetrating branches of vertebral artery). Magnetic
      resonance angiogram showed occlusion of the distal vertebral artery on the right
      side. Atherothrombotic occlusion of the distal vertebral artery may cause this
      unusual combination of vertebrobasilar stroke.

PMID- 15450777
TI  - Myasthenia gravis with thymus hyperplasia and pure red cell aplasia.
AB  - A case of myasthenia gravis (MG) with thymus hyperplasia and pure red cell
      aplasia (PRCA) is reported. A 57-year-old woman was diagnosed as having MG and
      was treated with thymectomy 26 years ago. The histology of the resected thymus
      was thymic lymphoid follicular hyperplasia. She developed rapidly progressive
      anemia and a bone marrow examination revealed PRCA. Her hematological results
      improved with oral administration of cyclosporine A. Cases of MG, thymoma and
      PRCA have been reported in the literature. We report the first case of MG without
      thymoma and PRCA.

PMID- 15450778
TI  - HIV-1 clade-C-associated "ALS"-like disorder: first report from India.
AB  - A patient of ALS-like disorder in an HIV-1 clade-C-infected heterosexual male is
      being reported. A 37-year-old gentleman presented with subacute, progressive
      asymmetrical onset of weakness and wasting of upper limbs associated with brisk
      muscle stretch reflexes and without any sensory or sphincter involvement. While
      nerve conduction tests were normal, the EMG of proximal and distal limb muscles
      on both sides revealed evidence of denervation and reinnervation. Routine blood
      and urine tests and investigations for underlying causes of motor neuron disease
      were noncontributory. He was HIV-1, subtype clade C seropositive. A diagnosis of
      HIV-related anterior horn cell disease was considered and zidovudine, lamivudine
      and nevirapine were started. After 1 month, there was a subjective improvement of
      10% and objective improvement in strength of muscles of proximal upper limb on
      both sides by one grade power on MRC scale. Reports of amyotrophic lateral
      sclerosis (ALS)-like illness in HIV are sparse. The reversibility of "ALS"-like
      features in this subgroup of patients might offer an insight into the
      pathogenesis of amyotrophic lateral sclerosis. This is a first report of ALS-like
      illness caused by subtype C of HIV-1 strain.

PMID- 15450779
TI  - Recurrent demyelinating myelitis associated with hepatitis C viral infection.
AB  - We report a 46-year-old-man who developed recurrent myelitis associated with
      hepatitis C viral (HCV) infection. Spinal cord biopsy showed acute demyelination
      without evidence of vasculitis. Antibodies to HCV were present in the CSF; HCV
      RNA was not detected in the CSF. Neither HCV antigens nor RNA were detected in
      the spinal cord biopsy, whereas they were found in the liver biopsy. Evaluation
      for other infectious or autoimmune causes was unrevealing. These observations
      suggest that recurrent myelitis in this patient is etiologically related to HCV
      infection, possibly via an immune-mediated mechanism. This is the first report of
      pathologically proven myelitis associated with HCV infection and we suggest that
      HCV be considered in the differential diagnosis of the transverse myelitis
      syndrome.

PMID- 15450780
TI  - Metronidazole-induced encephalopathy.
AB  - We report the clinical, neuropsychological, and neuroimaging findings of two
      patients of diffuse encephalopathy associated with the use of metronidazole. Both
      patients showed characteristic abnormalities on magnetic resonance imaging (MRI)
      with diffusion weighted imaging (DWI) and recovered incompletely after the
      discontinuation of metronidazole. We also suggest that MRI with DWI may be useful
      in the diagnosis of metronidazole-induced encephalopathy, and that they have a
      role in the prediction of prognosis.

PMID- 15450781
TI  - Reduced left anterior cingulate volumes in untreated bipolar patients.
AB  - BACKGROUND: Functional and morphologic abnormalities of the cingulate cortex have
      been reported in mood disorder patients. To examine the involvement of anatomic
      abnormalities of the cingulate in bipolar disorder, we measured the volumes of
      this structure in untreated and lithium-treated bipolar patients and healthy
      control subjects, using magnetic resonance imaging (MRI). METHODS: The volumes of
      gray matter at the right and left anterior and posterior cingulate cortices were
      measured in 11 bipolar patients not taking any psychotropic medications (aged 38
      +/- 11 years, 5 women), 16 bipolar patients treated with lithium monotherapy
      (aged 33 +/- 11 years, 7 women), and 39 healthy control subjects (aged 37 +/- 10
      years, 14 women). Volumetric measurements were made with T1-weighted coronal MRI
      images, with 1.5-mm-thick slices, at 1.5T, and were done blindly. RESULTS: Using
      analysis of covariance with age and intracranial volume as covariates, we found
      that untreated bipolar patients had decreased left anterior cingulate volumes
      compared with healthy control subjects [2.4 +/-.3 cm3 and 2.9 +/-.6 cm3,
      respectively; F(1,58) = 6.4, p =.042] and compared with lithium-treated patients
      [3.3 +/-.5 cm3; F(1,58) = 11.7, p =.003]. The cingulate volumes in lithium
      treated patients were not significantly different from those of healthy control
      subjects. CONCLUSIONS: Our findings indicate that anatomic abnormalities in left
      anterior cingulate are present in bipolar patients. Furthermore, our results
      suggest that lithium treatment might influence cingulate volumes in bipolar
      patients, which could possibly reflect postulated neuroprotective effects of
      lithium.

PMID- 15450782
TI  - A high prevalence of organ-specific autoimmunity in patients with bipolar
      disorder.
AB  - BACKGROUND: In a previous study, we reported an increased prevalence of
      thyroperoxidase antibodies (TPOA) in patients with bipolar disorder. Here we
      report the prevalence of other organ-specific autoantibodies: H/K adenosine
      triphosphatase (ATPA), glutamic acid decarboxylase-65 (GAD65A), and GAD-67
      (GAD67A). METHODS: ATPA, GAD65A, and GAD67A were determined (via a commercially
      available enzyme linked immunosorbent assay for ATPA, and a standardized radio
      immunoassays for GAD65A and GAD67A)in the sera of 239 patients with DSM-IV
      bipolar disorder, in 74 patients with DSM-IV schizophrenia, and in 220 healthy
      control subjects. RESULTS: The positivity prevalences for ATPA and GAD65A (but
      not GAD67A) were elevated in bipolar patients compared with those in healthy
      control subjects (11.7 vs. 6.1% and 11.3 vs. 2.6% respectively; p <.05).
      Schizophrenia patients did not show such statistically higher prevalence. The
      elevated prevalence of ATPA and GAD65A in bipolar disorder was associated with
      neither rapid cycling nor the use of lithium. Interestingly, the presence of
      GAD65A (and not that of TPOA and ATPA) tended to be associated with the activity
      of bipolar disorder. The level of TPOA was negatively correlated with the serum
      level of sIL-2R, a measure of T cell activation. CONCLUSION: Bipolar disorder is
      associated with organ-specific autoimmunity to the antigens TPO, H/K ATPase, and
      GAD65.

PMID- 15450783
TI  - Association of mitochondrial complex I subunit gene NDUFV2 at 18p11 with bipolar
      disorder in Japanese and the National Institute of Mental Health pedigrees.
AB  - BACKGROUND: Linkage with 18p11 is one of the replicated findings in molecular
      genetics of bipolar disorder. Because mitochondrial dysfunction has been
      suggested in bipolar disorder, NDUFV2 at 18p11, encoding a subunit of the complex
      I, reduced nicotinamide adenine dinucleotide (NADH)ubiquinone oxidoreductase, is
      a candidate gene for this disorder. We previously reported that a polymorphism in
      the upstream region of NDUFV2, -602G> A, was associated with bipolar disorder in
      Japanese subjects; however, functional significance of -602G> A was not known.
      METHODS: We screened the further upstream region of NDUFV2. We performed a case
      control study in Japanese patients with bipolar disorder and control subjects and
      a transmission disequilibrium test in 104 parent and proband trios of the
      National Institute of Mental Health (NIMH) Genetics Initiative pedigrees. We also
      performed the promoter assay to examine functional consequence of the -602G> A
      polymorphism. RESULTS: The -602G> A polymorphism was found to alter the promoter
      activity. We found that the other haplotype block surrounding -3542G> A was
      associated with bipolar disorder. The association of the haplotypes consisting of
      -602G> A and -3542G> A polymorphisms with bipolar disorder was seen both in
      Japanese case-control samples and NIMH trios. CONCLUSION: Together these findings
      indicate that the polymorphisms in the promoter region of NDUFV2 are a genetic
      risk factor for bipolar disorder by affecting promoter activity.

PMID- 15450784
TI  - Suicide attempt and n-3 fatty acid levels in red blood cells: a case control
      study in China.
AB  - BACKGROUND: Epidemiologic studies show that low fish intake is a risk factor of
      suicidality; however, there are no case-control studies investigating suicide
      attempt risk and tissue n-3 fatty acid levels. METHODS: We recruited 100 suicide
      attempt cases and another 100 control patients injured by accidents who were
      admitted to three hospitals affiliated with Dalian Medical University in Dalian,
      China. Case and control subjects were matched for age, gender, and smoking
      status. Those who were inebriated at the time of hospitalization were excluded.
      Blood was sampled immediately after admission to a hospital. Washed red blood
      cells (RBCs) were obtained, and the fatty acid composition of the total RBC
      phospholipid fraction was analyzed by gas chromatography. RESULTS:
      Eicosapentaenoic acid (EPA) levels in RBC in the case subjects were significantly
      lower than those of the control subjects (.74 +/-.52% vs. 1.06 +/-.62%, p
      <.0001). When the highest and lowest quartiles of EPA in RBC were compared, the
      odds ratios of suicide attempt was.12 in the highest quartile (95% confidence
      interval:.04-.36, p for trend =.0001) after adjustment for possible confounding
      factors CONCLUSIONS: Our findings suggest that low n-3 fatty acid levels in
      tissues were a risk factor of suicide attempt. Further studies including
      intervention with fish oil are warranted.

PMID- 15450785
TI  - Brain serotonin transporter availability predicts treatment response to selective
      serotonin reuptake inhibitors.
AB  - BACKGROUND: Few studies have investigated the predictive value of central
      serotonin transporter (SERT) availability for treatment response to serotonin
      reuptake inhibitors (SSRIs). This study used brain imaging to examine the
      relationship between pretreatment brain SERT availability and transporter
      occupancy by SSRIs with treatment response in two independent depressed
      populations. METHODS: Study 1: Twenty-three patients with major depression
      underwent a single photon emission computed tomography (SPECT) measurement of
      brain SERT availability using [123I]beta-CIT ([123I]methyl 3beta-(4-iodophenyl)
      tropane-2beta-carboxylate. The SERT availability was correlated with treatment
      response to fluoxetine (20 mg/day) assessed with weekly Hamilton Depression
      Rating Scale (HDRS) for 6 weeks. Study 2: The second group included 10 depressed
      patients who received 6 weeks of paroxetine treatment (20 mg/day) and serial
      SPECT scans (baseline, during, and after the treatment). RESULTS: In Study 1,
      higher pretreatment diencephalic SERT availability significantly predicted better
      treatment response 4 weeks later. Similar results were found in Study 2 and
      supported Study 1 findings. The data showed that greater occupancy of
      diencephalic transporters by paroxetine correlated with better treatment
      response. CONCLUSIONS: Higher pretreatment availability and greater occupancy of
      SERT in diencephalon may predict better treatment course in response to SSRIs.

PMID- 15450786
TI  - Tryptophan depletion reverses the therapeutic effect of selective serotonin
      reuptake inhibitors in social anxiety disorder.
AB  - BACKGROUND: Tryptophan depletion studies have suggested that central serotonin (5
      hydroxytryptamine, 5-HT) function mediates the therapeutic effect of selective
      serotonin reuptake inhibitors (SSRIs) in depression and panic disorder. The
      present study tested the hypothesis that temporary reduction in central 5-HT
      transmission, through acute tryptophan depletion, could reverse the therapeutic
      effect of the SSRIs in social anxiety disorder (SAD) patients. METHODS: Fourteen
      patients with SAD who showed sustained clinical improvement with SSRI treatment
      underwent tryptophan depletion in a double-blind, placebo-controlled, crossover
      design, over 2 days 1 week apart. At the peak time of depletion, the participants
      also underwent three behavioral challenges: autobiographical script, verbal task,
      and neutral script. Psychological outcome was assessed with the Spielberger State
      Anxiety Inventory (STAI) Form Y-1 and visual analog scales (VAS) measuring
      anxiety, depression, and somatic symptoms. RESULTS: Anxiety was significantly
      increased on the depletion day compared with the control day, both on the STAI
      Form Y-1 and composite VAS score. Furthermore, there was a significant depletion
      x time interaction, explained mainly by the anxiogenic effect of the
      autobiographical script. In contrast, the verbal and the neutral tasks failed to
      differentiate between depletion and placebo. CONCLUSIONS: Tryptophan depletion
      induced significant increase of anxiety in treated SAD patients, which was more
      prominent during the recital of an autobiographical script. This finding supports
      the notion that SSRIs improve social anxiety by increasing 5-HT availability. The
      autobiographical script seems to be a more robust challenge test for SAD than the
      stressful verbal task.

PMID- 15450787
TI  - Variation in catechol-o-methyltransferase val158 met genotype associated with
      schizotypy but not cognition: a population study in 543 young men.
AB  - BACKGROUND: Increased catechol-O-methyltransferase activity associated with
      variation in catechol-O-methyltransferase valine158 methionine genotypes may
      result in reduced dopamine neurotransmission in the prefrontal cortex and thus
      contribute to the poor performance of frontally mediated cognitive tasks and the
      occurrence of associated negative symptoms observed in patients with
      schizophrenia; however, reported associations between catechol-O
      methyltransferase valine158 methionine genotypes and measures of cognition have
      not been consistent. METHODS: Catechol-O-methyltransferase genotyping, measures
      of schizotypy, cognitive measures of memory and attention, as well as the
      antisaccade eye movement task, a measure sensitive to prefrontal cortical
      function, were obtained in a sample of 543 young men representative for that age
      group (mean age 21 years). RESULTS: None of the cognitive measures was associated
      with catechol-O-methyltransferase valine158 methionine genotypes; however, there
      was an effect of high-activity allele loading on schizotypy, in particular the
      negative and disorganization dimensions. CONCLUSIONS: Previously reported
      inconsistencies in the relationship between catechol-O-methyltransferase
      valine158 methionine genotypes and cognition were not resolved; however, catechol
      O-methyltransferase genotype may affect expression of negative schizotypy by
      direct or indirect effects on central dopamine neurotransmitter signaling.

PMID- 15450788
TI  - Functional differences among those high and low on a trait measure of
      psychopathy.
AB  - BACKGROUND: It has been established that individuals who score high on measures
      of psychopathy demonstrate difficulty when performing tasks requiring the
      interpretation of other's emotional states. The aim of this study was to
      elucidate the relation of emotion and cognition to individual differences on a
      standard psychopathy personality inventory (PPI) among a nonpsychiatric
      population. METHODS: Twenty participants completed the PPI. Following survey
      completion, a mean split of their scores on the emotional-interpersonal factor
      was performed, and participants were placed into a high or low group. Functional
      magnetic resonance imaging data were collected while participants performed a
      recognition task that required attention be given to either the affect or
      identity of target stimuli. RESULTS: No significant behavioral differences were
      found. In response to the affect recognition task, significant differences
      between high- and low-scoring subjects were observed in several subregions of the
      frontal cortex, as well as the amygdala. No significant differences were found
      between the groups in response to the identity recognition condition.
      CONCLUSIONS: Results indicate that participants scoring high on the PPI, although
      not behaviorally distinct, demonstrate a significantly different pattern of
      neural activity (as measured by blood oxygen level-dependent contrast)in response
      to tasks that require affective processing. The results suggest a unique neural
      signature associated with personality differences in a nonpsychiatric population.

PMID- 15450789
TI  - Docosahexaenoic acid reduces haloperidol-induced dyskinesias in mice: involvement
      of Nur77 and retinoid receptors.
AB  - BACKGROUND: Treatment of schizophrenia's symptoms with typical antipsychotic
      drugs shows some efficacy, but the induction of extrapyramidal symptoms
      represents a serious handicap, which considerably limits their usefulness. Recent
      evidence suggests that Nur77 (nerve growth factor-induced B) and retinoids are
      involved in biochemical and behavioral effects of antipsychotic drugs associated
      with striatal functions. METHODS: We evaluated the effect of retinoid ligands on
      oral dyskinesias (vacuous chewing movements) induced by haloperidol in wild-type
      and Nur77-deficient mice. RESULTS: Nur77 gene ablation (knockout) or
      administration of a retinoid antagonist induced vacuous chewing movements and
      exacerbated those induced by haloperidol, whereas the retinoid agonist
      docosahexaenoic acid (an omega-3 polyunsaturated fatty acid) reduced them. Both
      the prodyskinetic effect of the retinoid antagonist and the antidyskinetic effect
      of docosahexaenoic acid are dependent on the presence of Nur77, since these drugs
      remained inactive in Nur77 knockout mice. CONCLUSION: These results suggest that
      nuclear receptors Nur77 and retinoid X receptor are involved in haloperidol
      induced dyskinesias and that retinoid agonists may represent a new way to improve
      typical antipsychotic drug therapy.

PMID- 15450790
TI  - Perfusion abnormalities and decision making in cocaine dependence.
AB  - BACKGROUND: Previous studies have shown that cocaine abusers have cerebral
      perfusion deficits that may diminish cognitive functioning. This study examined
      whether cocaine-dependent patients have perfusion abnormalities associated with
      poor decision-making ability as measured by the Iowa Gambling Task (IGT).
      METHODS: Seventeen abstinent cocaine-dependent patients were administered the IGT
      after completion of resting 99mTc-HMPAO single-photon emission computed
      tomography (SPECT). RESULTS: Better IGT performance was negatively correlated
      with perfusion within the anterior cingulate gyrus, middle frontal gyrus, medial
      frontal gyrus, and superior frontal gyrus. The time to complete card selections
      was positively correlated with the severity of impairment. CONCLUSIONS: Resting
      hyperperfusion in brain regions previously implicated in decision making and
      response inhibition was associated with worse IGT scores. Impaired performance
      was related to a greater amount of time taken for card selections, suggesting
      that reduced ability was due to cognitive factors other than an impulsive
      response pattern.

PMID- 15450791
TI  - Increased cerebrospinal fluid corticotropin-releasing factor concentrations
      during tryptophan depletion in healthy adults.
AB  - BACKGROUND: Brain serotonin neurotransmission and hypothalamic-pituitary-adrenal
      axis function are implicated in the pathophysiology of depression, and these
      systems interact in a reciprocal modulatory fashion. This study examined the
      effect of tryptophan depletion, which acutely reduces brain serotonin
      concentrations, on serial cerebrospinal fluid concentrations of corticotropin
      releasing factor in healthy humans. METHODS: Five subjects completed a standard
      tryptophan depletion protocol, and four subjects participated in a comparison
      condition. Subjects underwent continuous sampling of cerebrospinal fluid via
      lumbar peristaltic pump. Concentrations of cerebrospinal fluid corticotropin
      releasing factor were measured by radioimmunoassay. RESULTS: No mood changes were
      observed in either group. Tryptophan-depleted subjects exhibited significantly
      greater increases in corticotropin-releasing factor concentrations over time than
      subjects in the comparison condition. CONCLUSIONS: These findings highlight the
      potential importance of corticotropin-releasing factor and serotonin interactions
      and suggest that activation of corticotropin-releasing-factor-containing neurons
      could play a role in the emergence of mood symptoms following tryptophan
      depletion in vulnerable individuals.

PMID- 15450792
TI  - Regarding "Combining norepinephrine and serotonin reuptake inhibition mechanisms
      for treatment of depression: a double-blind randomized study": Optimizing initial
      interventions.

PMID- 15450794
TI  - A static laser light scattering assay for surfactant-induced tau fibrillization.
AB  - Static light scattering is an important solution-based method for assaying
      spontaneous protein aggregation reactions. But the reliability of the
      measurements when conducted in the presence of fibrillization inducers has been
      questioned. Here the utility of static laser light scattering for quantitative
      assay of anionic micelle-induced protein fibrillization was characterized using
      tau protein, the major component of neurofibrillary lesions of Alzheimer's
      disease. Both inducer micellization and tau fibrillization made significant
      contributions to light scattering intensity. The intensity arising solely from
      micellization was quantified using proteins that promoted inducer micellization
      but could not fibrillize, such as mixed histones and assembly-incompetent mutant
      htau40(I277P/I308P). When corrected for micellization, reaction progress curves
      for wild-type tau fibrillization were sigmoidal and correlated well with
      measurements of total filament length made by transmission electron microscopy.
      The utility of the improved laser light scattering assay was demonstrated by
      quantifying the effect of inducer concentration on tau assembly kinetics using a
      three-parameter Gompertz growth function. Results showed that alkyl sulfate
      detergent accelerated tau nucleation as reflected by shorter lag times and
      modulated pre-nuclear equilibria to yield more filament mass at reaction
      equilibrium.

PMID- 15450795
TI  - Incorporation of integrins into artificial planar lipid membranes:
      characterization by plasmon-enhanced fluorescence spectroscopy.
AB  - An optimized peptide-tethered artificial lipid membrane system has been
      developed. Integrins (cell adhesion receptors) were functionally incorporated
      into this membrane model and integrin-ligand interactions were analyzed by
      surface plasmon-enhanced fluorescence spectroscopy (SPFS). The transmembrane
      receptors alpha(v)beta(3) and alpha(1)beta(1) of the integrin superfamily were
      incorporated into a lipid-functionalized peptide layer by vesicle spreading.
      Consecutive layer formations were monitored by surface plasmon spectroscopy
      (SPS). Orientation and accessibility of the membrane receptor alpha(v)beta(3) was
      reliably assessed by specific and reproducible binding of selective antibodies.
      Moreover, full retention of the functional properties of this receptor was
      verified by specific and reversible binding of natural ligands. Functional
      integrity of incorporated integrins was maintained over a time period of 72 h.
      The integrin/extracellular matrix ligand complexes, whose formations are known to
      depend on the presence of divalent cations, were lost upon addition of
      ethylenediaminetetraacetate. Therefore, regeneration of the surface for further
      binding experiments with minimized unspecific ligand association was possible.
      These results demonstrate that integrins can be functionally incorporated into
      peptide-tethered artificial membranes. In combination with the SPS/SPFS method,
      this artificial membrane system provides a reliable experimental platform for
      investigation of isolated membrane proteins under experimental conditions
      resembling those of their native environment.

PMID- 15450796
TI  - Determination of protein charge by capillary zone electrophoresis.
AB  - The feasibility of employing classical electrophoresis theory to determine the
      net charge (valence) of proteins by capillary zone electrophoresis is illustrated
      in this paper. An outline of a procedure to facilitate the interpretation of
      mobility measurements is demonstrated by its application to a published mobility
      measurement for Staphylococcal nuclease at pH 8.9 that had been obtained by
      capillary zone electrophoresis. The significantly higher valence of +7.5 (cf. 5.6
      from the same series of measurements) that has been reported on the basis of a
      "charge ladder" approach for charge determination signifies the likelihood that
      the latter generic approach may be prone to error arising from nonconformity of
      the experimental system with an inherent assumption that chemical modification or
      mutation of amino acid residues has no effect on the overall three-dimensional
      size and shape of the protein.

PMID- 15450797
TI  - Affinity purification of streptavidin using tobacco mosaic virus particles as
      purification tags.
AB  - A new protein affinity purification system has been developed. Recombinant
      tobacco mosaic virus (TMV) was used as an affinity matrix for isolation and
      purification of the given protein of interest. In model experiments, streptavidin
      specific heptapeptide sequence TLIAHPQ was inserted into TMV coat protein near
      the C end. This oligopeptide did not interfere significantly with viral
      replication, assembly, and movement. Recombinant TMV functioned as an epitope tag
      recognizing streptavidin in plant protein extracts. Plant protein extracts
      containing streptavidin were incubated with recombinant TMV virions. Affinity
      complexes of viral particles with the protein of interest were collected by
      centrifugation. Recombinant TMV-streptavidin complex was dissociated with 0.2M
      acetic acid, pH 4.6, and was passed through membrane filter Nanosep 300K by
      centrifugation. The filtrate contained pure streptavidin. Recombinant TMV was
      left on the filter. TMV particles collected from the filter could be used for at
      least two more purification cycles. The streptavidin-specific recombinant TMV
      system was applied successfully for purification of streptavidin from
      Streptomyces avidinii. The authors believe that the TMV-based affinity system can
      also be used for the purification of other proteins.

PMID- 15450798
TI  - Hair analysis of histamine after fluorescence labeling by column-switching
      reversed-phase liquid chromatography with electrospray ionization mass
      spectrometry and application to human hair.
AB  - Sensitive determination of histamine (HA) in hair was carried out by column
      switching reversed-phase high-performance liquid chromatography coupled with
      electrospray ionization mass spectrometry (HPLC-ESI-MS). HA was labeled with
      excess amounts of 4-(N,N-dimethylaminosulfonyl)-7-fluoro-2,1,3-benzoxadiazole
      (DBD-F) at 60 degrees C for 30 min in a mixture of 0.1 M borax (pH 9.3) and
      acetonitrile (CH(3)CN). The resulting DBD-HA derivative was roughly separated by
      a Mightysil RP-18 GP (100 x 2mm i.d., 3 microm) with an acidic mobile phase
      containing 0.1% trifluoroacetic acid. DBD-HA in the fraction flowing due to a
      position change in the six-port column-switching valve was then completely
      separated by a Wakopak Navi C30 (150 x 2mm i.d., 5 microm) with 20 mM AcONH(4)
      CH(3)CN (8:2). The mass spectrometer was operated in the selected reaction
      monitoring (SRM) mode for the product ion (m/z 292) obtained from MS-MS
      measurement using the protonated molecular ion [M+H](+) (m/z 337) as the
      precursor ion. Good linearity was achieved from the calibration curve obtained by
      plotting peak area ratios of the internal standard (HA-d(4)) against the injected
      amounts of HA (1.66-16.6 pmol, r(2)=0.999). The coefficients of variation, at
      1.66- and 16.6-pmol injections, were 5.6 and 3.7%, respectively (n=6).
      Furthermore, the detection limit was 0.167 pmol. The efficiency of the
      recommended procedure was identified from the determination in the rat hair root
      after intraperitoneal administration of HA. The proposed method was applied to HA
      determination in the hair shaft of Dark Agouti rats and healthy volunteers. The
      variations in the concentrations in 1mg of hair shaft were 0.80-1.84 pmol (mean+/
      SD=1.33+/-0.33, n=12) in rats and 0.94-72.3 pmol (17.2+/-21.5, n=16) in humans.
      The determination of HA in the plasma of rats and humans was also performed
      successfully by this method. Because the proposed method provides good precision
      and trace detection of HA in hair, the analytical technique seems to be
      applicable for the determination of various biogenic amines in hair.

PMID- 15450799
TI  - Characterization and applications of CataCleave probe in real-time detection
      assays.
AB  - Cycling probe technology (CPT), which utilizes a chimeric DNA-RNA-DNA probe and
      RNase H, is a rapid, isothermal probe amplification system for the detection of
      target DNA. Upon hybridization of the probe to its target DNA, RNase H cleaves
      the RNA portion of the DNA/RNA hybrid. Utilizing CPT, we designed a catalytically
      cleavable fluorescence probe (CataCleave probe) containing two internal
      fluorophores. Fluorescence intensity of the probe itself was weak due to Forster
      resonance energy transfer. Cleavage of the probe by RNase H in the presence of
      its target DNA caused enhancement of donor fluorescence, but this was not
      observed with nonspecific target DNA. Further, RNase H reactions with CataCleave
      probe exhibit a catalytic dose-dependent response to target DNA. This confirms
      the capability for the direct detection of specific target DNA through a signal
      amplification process. Moreover, CataCleave probe is also ideal for detecting DNA
      amplification processes, such as polymerase chain reaction (PCR) and isothermal
      rolling circle amplification (RCA). In fact, we observed signal enhancement
      proportional to the amount of RCA product formed. We were also able to monitor
      real-time PCR by measuring enhancement of donor fluorescence. Hence, CataCleave
      probe is useful for real-time monitoring of both isothermal and temperature
      cycling nucleic acid amplification methods.

PMID- 15450800
TI  - A nonradiometric, high-throughput assay for poly(ADP-ribose) glycohydrolase
      (PARG): application to inhibitor identification and evaluation.
AB  - The enzyme poly(ADP-ribose) glycohydrolase (PARG) catalyzes the hydrolysis of
      glycosidic bonds of ADP-ribose polymers, producing monomeric ADP-ribose units.
      Thus, in conjunction with poly(ADP-ribose) polymerase (PARP), PARG activity
      regulates the extent of in vivo poly(ADP-ribosyl)ation. Small molecule inhibitors
      of PARP and PARG have shown considerable promise in cellular models of ischemia
      reperfusion injury and oxidative neuronal cell death. However, currently
      available PARG inhibitors are not ideal due to cell permeability, size, and/or
      toxicity concerns; therefore, new small molecule inhibitors of this important
      enzyme are sorely needed. Existing methodologies for in vitro assessment of PARG
      enzymatic activity do not lend themselves to high-throughput screening
      applications, as they typically use a radiolabeled substrate and determine
      product quantities through TLC analysis. This article describes a method whereby
      the ADP-ribose product of the PARG-catalyzed reaction is converted into a
      fluorescent dye. This highly sensitive and reproducible method is demonstrated by
      identifying two known PARG inhibitors in a 384-well plate assay and by
      subsequently determining IC(50) values for these compounds. Thus, this high
      throughput, nonradioactive PARG assay should find widespread use in experiments
      directed toward identification of novel PARG inhibitors.

PMID- 15450801
TI  - A 384-well cell-based phospho-ERK assay for dopamine D2 and D3 receptors.
AB  - Phosphorylation of extracellular signal-regulated kinase (ERK) is linked to
      activation of many cell surface receptors and kinases. However, phosphorylated
      ERK has not been used as a biochemical marker to monitor pharmacology of these
      biomolecules, largely because commonly used methods to detect the phosphoprotein
      are not quantitative and do not have sufficient throughput. In this article, a
      high-throughput, 384-well, cell-based functional assay to quantify dopamine
      agonist-induced ERK phosphorylation in D2- and D3-overexpressed cell lines is
      described. The assay uses infrared-labeled secondary antibodies to detect phospho
      ERK, and the signals in the wells of the microtiter plate are quantified by a LI
      COR infrared scanner. V(max), EC(50), and functional K(i) values of various D2
      and D3 agonists and antagonists determined in this assay are similar to those in
      the literature. The assay is nonradioactive, is quantitative, and has a good
      signal-to-noise ratio. In addition, the signal is stable. This assay can be used
      to monitor the activities of many G protein-coupled receptors and other signaling
      biomolecules that are linked to phosphorylation of ERK. The methodology can
      potentially be used to detect the change in level of any cellular protein in
      which highly selective antibodies are available.

PMID- 15450802
TI  - Determination of the refractive index increment (dn/dc) of molecule and
      macromolecule solutions by surface plasmon resonance.
AB  - An automated method for dn/dc determination using a surface plasmon resonance
      instrument in tandem with a flow injection gradient system (FIG-SPR) is proposed.
      dn/dc determinations of small molecule and biomolecule, surfactant, polymer, and
      biopolymer solutions with precision around 1-2% and good accuracy were performed
      using the new method. dn/dc measurements were also carried out manually on a
      conventional SPR equipment with similar accuracy and precision. The FIG-SPR
      instrument is inexpensive and could be easily coupled to commercially available
      SPR and liquid chromatography instruments to obtain several properties of the
      solutions, which are based on measurements of refractive index.

PMID- 15450803
TI  - SPR-based interaction studies with small molecular weight ligands using hAGT
      fusion proteins.
AB  - An immobilization procedure for protein on surface plasmon resonance sensor (SPR)
      chips is described. The target protein, cyclophilin D, is thereby genetically
      linked to a mutant of the human DNA repair protein O(6)-alkylguanine-DNA
      alkyltransferase (hAGT). The procedure includes the immobilization of an
      alkylguanine derivative on the surface by amine coupling and contact of the
      surface with a solution of the fusion protein (TCypD-hAGT). TCypD-hAGT could be
      immobilized using buffer solutions of purified protein or cell extracts. High
      densities of covalently linked proteins were achieved by either procedure.
      Binding experiments performed with the ligand cyclosporin A indicate relative
      binding activities close to 100%. The K(D) value (12 nM) and the kinetic rate
      constants k(on) (3 x 10(5)M(-1)s(-1)) and k(off) (4 x 10(-3)s(-1)) are given and
      compared to values determined for cyclophilin D linked to the surface by amide
      coupling chemistry. The K(D) value is in excellent agreement with the K(D) value
      determined in solution by fluorescence titration.

PMID- 15450804
TI  - A subnanogram assay for phospholipase activity based on a long-chain
      radioiodinatable phosphatidylcholine.
AB  - Here, we introduce a radioiodinatable long-chain phosphatidylcholine (BHC12PC)
      which serves as the base for a very sensitive phospholipase assay. This compound
      has a 4-hydroxyphenyl group attached at the end of the fatty acyl chain located
      in position sn-2. This feature enables this phospholipid to be radioiodinated.
      BHC12PC was tested as a substrate of Naja naja naja PLA(2) and Bacillus cereus
      PLC in a mixed micellar system with Triton X-100. The detection limit for the
      assays was 0.25ng of PLA(2) and 0.05ng of PLC, thus becoming one of the most
      sensitive methods described so far. A low specific radioactivity
      (500microCi/mmol) suffices to achieve this level of sensitivity. In both cases,
      the behavior of BHC12PC was indistinguishable from that shown by phospholipids
      with n-acyl chains of similar length. The choice of spacer prevents any
      unfavorable interaction of the bulky 4-hydroxyphenyl group at the active site of
      the enzymes. The progress of the reaction as monitored by thin-layer
      chromatography is compared side by side with an alternative method based on the
      selective adsorption of BHC12PC to silica gel, which renders identical results in
      a simpler fashion. An additional advantage of BHC12PC is that the cost per Ci of
      the radioiodinated derivative is significantly lower than that of other labeled
      phospholipids ((3)H, (14)C, or (32)P).

PMID- 15450805
TI  - Detection of cariogenic bacteria genes by a combination of allele-specific
      polymerase chain reactions and a novel bioluminescent pyrophosphate assay.
AB  - We developed a novel bioluminescent assay for detection of pyrophosphate in
      polymerase chain reaction (PCR) product. The principle of this method is as
      follows: pyrophosphate released by PCR is converted to adenosine 5'-triphosphate
      (ATP) by pyruvate phosphate dikinase in the presence of the substrate pyruvate
      phosphate and the coenzyme adenosine 5'-monophosphate; subsequently, ATP
      concentration is determined by firefly luciferase reaction. The detection limit
      of pyrophosphate is 1.56 x 10(-15)mol/assay. Additionally, luminescent intensity
      reached a maximum at approximately 100 s and remained elevated beyond 10 min.
      This approach is applicable to the detection of cariogenic bacteria in dental
      plaque. Thus, the allele-specific PCR products of Streptococcus mutans and
      Streptococcus sobrinus developed in this study were measured via the proposed
      bioluminescent assay. This protocol, which does not require expensive equipment,
      can be utilized to rapidly monitor cariogenic bacteria in dental plaque.

PMID- 15450806
TI  - Chemiluminescent assay for detection of viable microorganisms.
AB  - The redox reaction between quinone and viable microorganisms produces active
      oxygen species. In this study, the production rates of active oxygen species were
      determined by a luminol chemiluminescent assay, and the luminescence intensity
      was found to be proportional to the viable cell number. The high sensitivity of
      the luminol chemiluminescent assay was achieved with Mo
      ethylenediaminetetraacetate complex and menadione or coenzyme Q1. The detectable
      cell densities of bacteria and yeasts were found to be approximately several
      thousand colony-forming units (CFU/ml) when assays were performed with a 96-well
      microplate luminometer. The chemiluminescent assay requires 10 min for incubation
      of quinone and microorganisms and 2s for photon counting. Single Escherichia coli
      was detected after 4h of cultivation and centrifugation (5 min x 2). This simple
      chemiluminescent assay is expected to be useful for the rapid detection of viable
      bacteria and yeast.

PMID- 15450807
TI  - Ligation detection reaction-TaqMan procedure for single nucleotide polymorphism
      detection on genomic DNA.
AB  - In this article, we describe a genotyping approach applicable to both individual
      and multiplexed single nucleotide polymorphism (SNP) analysis, based on a
      ligation detection reaction (LDR) performed directly on genomic DNA. During the
      ligation, the biallelic state of the SNP locus is converted into a bimarker state
      of ligated detector oligonucleotides. The state of the markers is then determined
      by a 5'-nuclease assay (TaqMan) with universal fluorescent probes. The LDR-TaqMan
      method was successfully applied for the genotyping of 30 SNP loci of Arabidopsis
      thaliana. The technology is cost-effective, needs no locus-specific optimization,
      requires minimal manipulations, and has very good potential for automation.

PMID- 15450808
TI  - Assay for glucose oxidase from Aspergillus niger and Penicillium amagasakiense by
      Fourier transform infrared spectroscopy.
AB  - A simple and direct assay method for glucose oxidase (EC 1.1.3.4) from
      Aspergillus niger and Penicillium amagasakiense was investigated by Fourier
      transform infrared spectroscopy. This enzyme catalyzed the oxidation of d-glucose
      at carbon 1 into d-glucono-1,5-lactone and hydrogen peroxide in phosphate buffer
      in deuterium oxide ((2)H(2)O). The intensity of the d-glucono-1,5-lactone band
      maximum at 1212 cm(-1) due to CO stretching vibration was measured as a function
      of time to study the kinetics of d-glucose oxidation. The extinction coefficient
      epsilon of d-glucono-1,5-lactone was determined to be 1.28 mM(-1)cm(-1). The
      initial velocity is proportional to the enzyme concentration by using glucose
      oxidase from both A. niger and P. amagasakiense either as cell-free extracts or
      as purified enzyme preparations. The kinetic constants (V(max), K(m), k(cat), and
      k(cat)/K(m)) determined by Lineweaver-Burk plot were 433.78+/-59.87U mg(-1)
      protein, 10.07+/-1.75 mM, 1095.07+/-151.19s(-1), and 108.74 s(-1)mM(-1),
      respectively. These data are in agreement with the results obtained by a
      spectrophotometric method using a linked assay based on horseradish peroxidase in
      aqueous media: 470.36+/-42.83U mg(-1) protein, 6.47+/-0.85 mM, 1187.77+/-108.16s(
      1), and 183.58 s(-1)mM(-1) for V(max), K(m), k(cat), and k(cat)/K(m),
      respectively. Therefore, this spectroscopic method is highly suited to assay for
      glucose oxidase activity and its kinetic parameters by using either cell-free
      extracts or purified enzyme preparations with an additional advantage of
      performing a real-time measurement of glucose oxidase activity.

PMID- 15450809
TI  - Application of solid-phase microextraction combined with derivatization to the
      determination of amphetamines by liquid chromatography.
AB  - This work evaluates the utility of solid-phase microextraction (SPME) in the
      analysis of amphetamines by liquid chromatography (LC) after chemical
      derivatization of the analytes. Two approaches have been tested and compared,
      SPME followed by on-fiber derivatization of the extracted amphetamines, and
      solution derivatization followed by SPME of the derivatives formed. Both methods
      have been applied to measure amphetamine (AP), methamphetamine (MA), and 3,4
      methylenedioxymethamphetamine (MDMA), using the fluorogenic reagent 9
      fluorenylmethyl chloroformate (FMOC) and carbowax-templated resin (CW-TR)-coated
      fibers. Data on the application of the proposed methods for the analysis of
      different kind of samples are presented. When analyzing aqueous solutions of the
      analytes, both approaches gave similar analytical performance, but the
      sensitivity attainable with the solution derivatization/SPME method was better.
      The efficiencies observed when processing spiked urine samples by the SPME/on
      fiber derivatization approach were very low. This was because the extraction of
      matrix components into the fiber coating prevented the extraction of the reagent.
      In contrast, the efficiencies obtained for spiked urine samples by the solution
      derivatization/SPME approach were similar to those obtained for aqueous samples.
      Therefore, the later method would be the method of choice for the quantification
      of amphetamines in urine.

PMID- 15450810
TI  - Clinical analysis of vitamin B(6): determination of pyridoxal 5'-phosphate and 4
      pyridoxic acid in human serum by reversed-phase high-performance liquid
      chromatography with chlorite postcolumn derivatization.
AB  - A reversed-phase high-performance liquid chromatography (HPLC) method with
      fluorometric detection was developed for the routine determination of pyridoxal
      5'-phosphate (PLP) and 4-pyridoxic acid (4-PA) in serum. Chlorite postcolumn
      derivatization was used to oxidize PLP to a more fluorescent carboxylic acid
      form. Sensitivity improved fourfold for PLP using chlorite postcolumn
      derivatization over traditional bisulfite postcolumn derivatization. The HPLC
      injection cycle was 15 min, facilitating a throughput of 60 patient samples (72
      injections that included standards and quality control (QC) samples) in 18.5h.
      Method precision was evaluated using three serum QC pools with PLP and 4-PA
      concentrations of 11.5-34.8 nmol/L and 10.4-21.0 nmol/L, respectively. Within-run
      (n=7) repeatabilities were 0.6-1.2% for PLP and 0.9-1.8% for 4-PA. Run-to-run
      (n=23) reproducibilities were 3.6-6.7% for PLP and 3.7-5.6% for 4-PA. Relative
      detection (3sigma(0)) and quantitation (10sigma(0)) limits were 0.3 and 0.9
      nmol/L, respectively, for both PLP and 4-PA using a 10-microl sample injection
      volume. Analytical recoveries ranged from 97 to 102%. Patient-matched serum and
      plasma specimens (n=25) were analyzed to evaluate specimen-type bias. Of the
      plasma types evaluated, heparinized plasma introduced the lowest relative bias
      for PLP (-5.3%) and minimal bias for 4-PA (-2.3%) compared with serum.
      Ethylenediaminetetraacetic acid (EDTA) plasma showed the lowest bias for 4-PA
      (0.7%) but a relatively high bias for PLP (13.0%) due to a chromatographic
      interference. Human serum samples from a non-representative population subset
      (n=303) were commensurate with values published for other vitamin B(6) HPLC
      methods. These values gave geometric means of 42.4 nmol/L for PLP and 27.3 nmol/L
      for 4-PA. Medians for PLP and 4-PA were 40.1 and 21.8 nmol/L, respectively. The
      high sensitivity, precision, and throughput of this method, combined with its
      minimal serum specimen (150 microl) and sample injection (10 microl) volume
      requirements, make it well suited for routine clinical vitamin B(6) analysis.

PMID- 15450811
TI  - Novel potentiometric immunosensor for hepatitis B surface antigen using a gold
      nanoparticle-based biomolecular immobilization method.
AB  - A novel potentiometric immunosensor for the detection of hepatitis B surface
      antigen has been developed by means of self-assembly to immobilize hepatitis B
      surface antibody on a platinum disk electrode based on gold nanoparticles,
      Nafion, and gelatin as matrices in this study. The modification procedure of the
      immunosensor was further characterized by using cyclic voltammetry and the enzyme
      linked immunosorbent assay (ELISA) method. The detection is based on the change
      in the electric potential before and after the antigen-antibody reaction. In
      contrast to the commonly applied methods (e.g., the glutaraldehyde crosslinking
      procedure), this strategy could allow for antibodies immobilized with a higher
      loading amount and better retained immunoactivity, as demonstrated by the
      potentiometric measurements. A dynamic concentration range of 4-800 ng ml(-1) and
      a detection limit of 1.3 ng ml(-1) were observed. Analytical results of several
      human serum samples obtained using the developing technique are in satisfactory
      agreement with those given by ELISA. In addition, the technique presents some
      distinct advantages over the traditional sandwich format in that the analyzing
      performances are direct, rapid, and simple without multiple separation and
      labeling steps.

PMID- 15450812
TI  - Accentuation of differentially expressed proteins using phage technology.
AB  - Protein profiling is frequently used to elucidate disease-specific or
      differentially expressed proteins. While recent developments have resulted in
      improved differential profiling, alternative expression platforms that complement
      existing techniques are continually being explored. We developed a novel method
      utilizing the amplification and selection capabilities of random peptide
      expressing M13 bacteriophage to accentuate differentially expressed proteins in
      biologic specimens. While the current study used this method to demonstrate
      differentially expressed proteins in lung cancer tissue in comparison to normal
      lung tissue, this approach is applicable to a wide range of sample types.

PMID- 15450813
TI  - Pure translation display.
AB  - Methods such as monoclonal antibody technology, phage display, and ribosome
      display provide genetic routes to the selection of proteins and peptides with
      desired properties. However, extension to polymers of unnatural amino acids is
      problematic because the translation step is always performed in vivo or in crude
      extracts in the face of competition from natural amino acids. Here, we address
      this restriction using a pure translation system in which aminoacyl-tRNA
      synthetases and other competitors are deliberately omitted. First, we show that
      such a simplified system can synthesize long polypeptides. Second, we demonstrate
      "pure translation display" by selecting from an mRNA library only those mRNAs
      that encode a selectable unnatural amino acid upstream of a peptide spacer
      sequence long enough to span the ribosome tunnel. Pure translation display should
      enable the directed evolution of peptide analogs with desirable catalytic or
      pharmacological properties.

PMID- 15450814
TI  - Molecular characterization of monovalent and multivalent hapten-protein
      conjugates for analysis of the antigen--antibody interaction.
AB  - We prepared a hapten-protein conjugate using (4-hydroxy-3-nitrophenyl)acetyl (NP)
      hapten and hen egg lysozyme (HEL) or bovine serum albumin (BSA) and defined
      hapten modification sites on the former protein based on results of reverse-phase
      high-performance liquid chromatography (HPLC) and mass spectrometric analyses
      performed after enzymatic digestion. The most reactive residue for
      aminoacetylation in HEL was found to be Lys33, and the second was Lys96 or Lys97.
      The homogeneous NP-HEL conjugates were purified by HPLC and used for examining
      the effect of hapten valence on the antigen-antibody interaction. We also
      examined the molecular nature of NP conjugates of BSA. Analysis using mass
      spectroscopy showed that the mass distribution of NP-BSA conjugates was limited,
      although it became broader with an increase in NP valence. Surface plasmon
      resonance biosensor measurements were employed in measuring antigen-antibody
      interactions. The results showed that the apparent binding avidity depends on
      hapten valence, hapten density, size of carrier proteins, and intrinsic binding
      affinity of the antibody.

PMID- 15450815
TI  - An in vitro screening assay based on synthetic prion protein peptides for
      identification of fibril-interfering compounds.
AB  - Transmissible spongiform encephalopathies are neurodegenerative diseases and are
      considered to be caused by malformed prion proteins accumulated into fibrillar
      structures that can then aggregate to form larger deposits or amyloid plaques.
      The identification of fibril-interfering compounds is of therapeutic and
      prophylactic interest. A robust and easy-to-perform, high-throughput, in vitro
      fluorescence assay was developed for the detection of such compounds. The assay
      was based on staining with the fluorescent probe thioflavin S in polystyrene
      microtiter plates to determine the amyloid state of synthetic peptides,
      representing a putative transmembrane domain of human and mouse prion protein. In
      determining optimal test conditions, it was found that drying peptides from
      phosphate buffer prior to staining resulted in good reproducibility with an
      interassay variation coefficient of 8%. Effects of thioflavin S concentration and
      staining time were established. At optimal thioflavin S concentration of
      0.2mg/ml, the fluorescence signals of thioflavin S with five different prion
      protein-based fibrillogenic peptides, as well as peptide Abeta((1-42)), were
      found to show a peptide-dependent linear correlation within a peptide
      concentration range of 10-400 microM. The ability of the assay to identify
      compounds that interfere with fibril formation and/or dissociate preformed
      fibrils was demonstrated for tetracyclic compounds by preceding coincubation with
      human prion protein peptide huPrP106-126.

PMID- 15450816
TI  - Affinity depletion of albumin from human cerebrospinal fluid using Cibacron-blue
      3G-A-derivatized photopatterned copolymer in a microfluidic device.
AB  - In the context of proteomic research, affinity separations for the
      prefractionation of complex mixtures, such as cell lysates or human tissues, have
      become increasingly important. Microfluidic devices have shown significant
      potential to achieve fast analysis and low sample consumption. Here, we
      demonstrate the use of a microfluidic device to achieve affinity capture of
      albumin from human cerebrospinal fluid. Traditional photolithography and wet
      etching techniques were used to fabricate devices from borosilicate glass wafers.
      Monolithic porous polymer was prepared in a microfluidic channel by
      photopolymerization of glycidyl methacrylate and trimethylolpropane
      trimethacrylate. After derivatization with Cibacron-blue-3G-A, the modified
      polymer was used to achieve affinity capture of lysozyme and human albumin. Both
      fluorescence detection and matrix-assisted laser desorption ionization time of
      flight mass spectrometry were used to validate the results.

PMID- 15450817
TI  - High-throughput methods for measuring heparanase activity and screening potential
      antimetastatic and anti-inflammatory agents.
AB  - Heparanase plays an important role in the degradation of the extracellular
      matrix. It is implicated in inflammation, tumor angiogenesis and metastasis. We
      have developed two high-throughput methods for measuring heparanase activity and
      screening potential inhibitors. The first method involves coating fibroblast
      growth factor (FGF) on microtiter plates and capturing fluorescein isothiocyanate
      (FITC)-labeled heparin sulfate (HS), which is used as a substrate for heparanase
      digestion. Labeled HS fragments are released into the medium and quantitated by
      fluorescence intensity measurement. We have implemented this assay method into a
      Zeiss uHTS system and screened compound libraries for heparanase inhibitors. The
      second method involves labeling HS with biotin followed by FITC to generate a
      dual-labeled HS. The labeled material is bound to streptavidin-coated plates and
      used as a substrate for heparanase digestion. Both methods are sensitive and
      easily applicable to robotic systems. In addition, we have labeled both HS and
      biotin-HS with Eu-chelate, a fluorophore that exhibits long decay fluorescence.
      Assays using Eu-labeled HS and Eu-labeled biotin-HS have been developed and show
      higher sensitivity than those using FITC-labeled material. Furthermore, assays
      using Eu-chelate HS (or biotin-HS) should eliminate the interference of
      fluorescence compounds.

PMID- 15450818
TI  - Cell-based assay for monitoring transglutaminase activity.

PMID- 15450819
TI  - A bioluminescent DNA nickase assay of deoxyribonuclease I.

PMID- 15450820
TI  - Volume errors in isothermal titration calorimetry.

PMID- 15450821
TI  - A nationwide study of conversion from laparoscopic to open cholecystectomy.
AB  - PURPOSE: To determine the national incidence and risk factors for conversion from
      laparoscopic to open cholecystectomy. BACKGROUND: Most series reporting the rates
      at which laparoscopic cholecystectomies are performed, relative to the open
      procedure, have come from centers specializing in laparoscopic surgery. The rates
      at which conversions occur from these centers may not reflect those in community
      practice. We sought to determine the actual, and therefore acceptable, conversion
      rate by examining nationally representative discharge data. METHODS: The National
      Hospital Discharge database for 1998 to 2001 was acquired from the Centers for
      Disease Control. All gallbladder disease related admissions were extracted, and
      the cholecystectomies (ICD-9-CM codes 51.2X) were analyzed using the SAS package.
      Stepwise logistic regression was used to determine what factors were associated
      with the risk of conversion from laparoscopic to open cholecystectomy. RESULTS:
      Approximately 25% of all cholecystectomies are performed by the open technique.
      Of the remaining 75%, there is an approximately 5% to 10% conversion rate. The
      major risk factors for conversion included male sex, obesity, and cholecystitis.
      Concurrent choledocholithiasis, cholelithiasis, and cholecystitis were associated
      with a conversion rate of 25%. Length of stay (LOS) was reduced for laparoscopic
      operations and although conversion added 2 to 3 days to the LOS, for most cases
      the LOS was still less than for primary open operations. CONCLUSIONS: Three
      quarters of all cholecystectomies are performed laparoscopically, and the
      national conversion rate is 5% to 10%. Cholecystitis, choledocholithiasis, male
      sex, and obesity are major predictors for conversion. The data presented in terms
      of conversion rates and LOS were derived from population-adjusted hospital
      discharge data and represent the current U.S. experience for cholecystectomy.
      From these data the community experience for conversion rates, risk factors, and
      LOS can be derived.

PMID- 15450822
TI  - Benefit/risk profile of drotrecogin alfa (activated) in surgical patients with
      severe sepsis.
AB  - BACKGROUND: The Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) trial
      examined the safety and efficacy of drotrecogin alfa (activated) (Xigris) in
      adult patients with severe sepsis. A clinical evaluation committee examined
      clinical data for each patient enrolled in PROWESS. However, there were no
      surgeons on the committee, and thus questions remained regarding the safety and
      efficacy of drotrecogin alfa (activated) in surgical patients. METHODS: Masked to
      treatment, a Surgical Evaluation Committee adjudicated the presence and type of
      operation, timing of surgery, infection, and adequacy of source control of
      surgical patients included in PROWESS. RESULTS: Twenty-eight percent of PROWESS
      cases were confirmed as surgical. The absolute risk reduction for mortality in
      all surgical patients was 3.2% and 9.1% for patients undergoing intraabdominal
      procedures. Serious bleeding during the infusion and 28-day period was similar
      between surgical and nonsurgical patients. CONCLUSIONS: Consistent with the
      overall PROWESS results, drotrecogin alfa (activated) has a favorable
      benefit/risk profile in surgical patients.

PMID- 15450823
TI  - Progressive adoption of cryoablative therapy for breast fibroadenoma in community
      practice.
AB  - BACKGROUND: Cryoablation is a recent technological advance and has been used for
      the percutaneous treatment of breast fibroadenomas. Herein, we provide a
      retrospective summary of the early experience from a nationwide group. METHODS:
      We organized a national registry to document the community practice and adoption
      of an office-based system of cryoablation for breast fibroadenoma. Data were
      abstracted during the first 6 weeks after the procedure to assess acute outcome
      and potential complications. At 6-and 12-month follow-up intervals, additional
      data were collected regarding fibroadenoma resolution, cosmesis, and patient
      satisfaction. RESULTS: Fifty-three sites ablated 310 fibroadenomas. Early follow
      up data on 256 lesions showed that the procedure was well tolerated with
      infrequent minor complications immediately after the procedure. At 6 and 12
      months postprocedure, the remaining fibroadenoma volume progressively involuted.
      At both intervals, cosmesis was excellent, and patient satisfaction was rated
      high. CONCLUSIONS: An early community experience with office-based cryoablation
      of breast fibroadenomas is encouraging and comparable to the initial experience
      of high-volume tertiary centers. More follow-up is necessary to determine long
      term results and residual mammographic changes.

PMID- 15450824
TI  - What do surgery residents do on their call nights?
AB  - BACKGROUND: Surgical resident education is entering a critical era of achieving
      core competencies despite work hour restrictions. An assessment of on-call
      activity is needed to maximize educational merit. METHODS: A time-motion study of
      resident on-call activity was performed at a university medical center and an
      urban affiliate hospital. Residents were followed by "shadow" residents who
      concurrently recorded resident activity. RESULTS: Activities of daily living and
      patient evaluation comprised the majority of on-call activity. Residents slept a
      median of 200 minutes per night. Cross-coverage activities accounted for 41% of
      pages and 19% of patient evaluation. Direct patient contact comprised only 7% of
      call night duties. Communication activity occupied 15% of total minutes, and a
      mean of 16 pages were received nightly. Significant differences in activities
      existed between resident levels and hospitals. CONCLUSIONS: Call activity
      consists primarily of activities of daily living, patient evaluation, and
      communication. Sleep accounts for nearly one third of all on-call activity. These
      data may be useful in improving both patient care and resident call experience.

PMID- 15450825
TI  - Study habits of surgery residents and performance on American Board of Surgery In
      Training examinations.
AB  - BACKGROUND: The purpose of this study was to evaluate the study habits (SHs) of
      surgery residents preparing for the annual American Board of Surgery In-Training
      Examination (ABSITE). METHODS: A validated instrument developed to assess SHs in
      college students, the Survey of Study Habits and Attitudes (SSHA), was modified
      slightly for use with residents. The modified SSHA contains 2 subscale scores,
      work methods and delay avoidance, and a combined overall study habit score. A
      total of 59 residents from 2 academic general surgical residency programs were
      administered the modified SSHA. The SSHA scores were correlated to performance on
      the in-training examination. RESULTS: There was a small but significant
      correlation between scores on the modified SSHA instrument and performance on the
      ABSITE overall (r = 0.29; P < .05; r2 = 0.0841). Linear-regression analysis
      showed that the clinical component and overall performance on the ABSITE were
      significantly predicted by the total SH scores. Overall total ABSITE percent
      correct scores were significantly predicted by residency levels of training and
      the overall SSHA scales (delay avoidance and work methods). Together they
      predicted 63% of the total variance in the overall performance scores. Residency
      level was the strongest predictor. SH performance accounted for 5.9% of the total
      variance beyond that contributed by residency level of training. CONCLUSIONS: The
      correlations of surgical resident ABSITE performance with SSHA scores were on the
      same order of magnitude as those of college students and academic performance
      with the original SSHA. Although SH in this study accounted for a measurable yet
      small contribution to ABSITE performance, this contribution was not enough to
      consider using the SSHA instrument in its current modified form as a diagnostic
      and counseling tool. Published instruments not specifically designed for
      residents may not be tailored enough to measure residents' unique SH.

PMID- 15450826
TI  - Temporary bacteremia due to intraoperative blood salvage during cardiovascular
      surgery.
AB  - BACKGROUND: The significance of positive blood cultures obtained after
      intraoperative blood salvage is unclear. METHODS: Sixty-four patients who
      underwent cardiopulmonary bypass and 52 patients with use of a blood salvage
      device underwent blood culture and examination of inflammatory responses.
      RESULTS: Positive blood cultures of transfused blood were identified in 16% of
      patients who underwent cardiopulmonary bypass and 67% with blood salvage.
      Thoracic operations utilizing either device demonstrated positive cultures in 21%
      of cases, whereas 70% of abdominal operations demonstrated positive cultures.
      However, on postoperative day 1, all blood cultures were negative. In addition,
      there was no significant difference in the inflammatory responses between culture
      positive and culture-negative groups. CONCLUSIONS: Although there is a high
      incidence of positive blood culture present during blood salvage and abdominal
      surgery, postoperative host responses are similar in both groups. These data
      support the safe use of intraoperative blood salvage in elective cardiovascular
      surgery with attention to routine sterile technique.

PMID- 15450827
TI  - An analysis of 124 surgically managed brachial artery injuries.
AB  - BACKGROUND: A 3-year review of surgically managed brachial artery injuries is
      presented. METHODS: The medical records were analyzed for demographic data,
      mechanism of injury, associated injuries, treatment, and outcome. RESULTS: There
      were 113 males and 11 females with a mean age of 28.7 years. The majority of the
      injuries were caused by stab and gunshot wounds in 57.3% and 29%, respectively.
      Primary anastomosis was possible in 47 patients, whereas 73 patients required
      vein interposition grafting. Lower arm fasciotomy was performed in 15 patients
      (12.1%). Associated injuries included peripheral nerve lesions in 77 (62.1%),
      nonpaired brachial vein injuries in 17 (13.7%), and concomitant humerus fracture
      in 12 (9.7%) patients. Thirty-nine patients (31.5%) had remote injuries.
      CONCLUSIONS: The primary repair of penetrating brachial artery injuries was
      possible in approximately one third of the patients. Approximately two thirds of
      the patients had associated nerve lesions. Critical limb ischemia rarely
      occurred.

PMID- 15450828
TI  - Medical student electives in general surgical subspecialties.
AB  - BACKGROUND: The purpose of the study was to evaluate how well the burn, trauma,
      and peripheral vascular third-year medical school electives meet the objectives
      of the six ACGME core competencies. METHODS: Medical school graduates from 1999
      to 2002 completed a survey that consisted of 13 demographic/miscellaneous
      questions, and 28 core competency questions. RESULTS: In all, 168 of 500 students
      responded for a 34% response rate. All three general surgical electives ranked
      above average in meeting objectives in the areas of: basic science, performing
      complete histories and physicals, writing logical and legible notes, creating
      complete assessments and plan, making decisions with evidence based medicine,
      performing basic procedures, interpreting test results, and maintaining
      professional attitudes. The burn elective ranked significantly higher in 16 of 28
      objectives (P < 0.05) and the trauma elective ranked significantly higher in two
      of 28 objectives (P < 0.05). CONCLUSIONS: Despite a narrower professional focus,
      three general surgical subspecialty electives meet objectives in five of the six
      competencies set forth by the ACGME (and adopted by our medical school as
      objectives for the ideal graduate). The highly organized and structured burn
      elective can be used as a template for improving all surgical rotations to meet
      the six core competencies for third-year students.

PMID- 15450829
TI  - The impact of low health literacy on surgical practice.
AB  - BACKGROUND: We sought to determine the prevalence of low health literacy (LHL)
      among patients in a preoperative clinic, the characteristics associated with LHL,
      and the association between LHL and adherence to preoperative instructions.
      METHODS: We conducted a cohort study and interviewed patients at a VA
      preoperative clinic. We administered a health literacy test and collected
      sociodemographic information. When patients returned for their scheduled surgical
      procedures, adherence to preoperative instructions was assessed. RESULTS: Of 332
      participants, 12% (n = 40) had LHL. Low health literacy was more prevalent among
      older adults (more than 65 years) compared with those under age 65. Patients with
      LHL were more likely to be nonadherent to preoperative medication instructions
      (odds ratio = 1.9; 95% confidence interval: 0.8 to 4.8), but this was of
      borderline statistical significance. CONCLUSIONS: Low health literacy was common
      among older patients and appeared to be associated with lower adherence to
      preoperative medication instructions.

PMID- 15450830
TI  - En-bloc esophagectomy for esophageal cancer.
AB  - BACKGROUND: The operative approach for esophageal cancer varies from simple
      palliative resection to extended esophagectomy with 3-field lymph-node dissection
      or en-bloc esophagectomy (EBE) depending on tumor and patient status and surgical
      strategy of the surgeon. The merits and demerits of such EBE are yet to be
      determined. METHODS: A literature review was done regarding EBE for esophageal
      cancer. RESULTS: Twenty articles describing EBE were reported from experienced
      institutions during the last 20 years and were selected for this study. The
      conclusions drawn from those articles showed that EBE would be a safe procedure
      with acceptable morbidity and low mortality rates when performed by an
      experienced surgeon. When strict patient selection criteria were maintained, this
      procedure decreased locoregional recurrence and improved long-term survival
      rates. CONCLUSIONS: EBE would be the treatment of choice in selected patients
      presenting with esophageal cancer. Development of meticulous preoperative risk
      assessment and optimum postoperative care may further improve the acceptability
      of this procedure with minimum morbidity and acceptable mortality rates.

PMID- 15450831
TI  - Salvage esophagectomy after definitive chemotherapy and radiotherapy for advanced
      esophageal cancer.
AB  - BACKGROUND: Although local recurrence of advanced esophageal cancer is frequent
      after definitive chemoradiotherapy (CRT), the clinical benefit of salvage
      esophagectomy has not been elucidated. METHODS: We reviewed 27 patients with
      squamous-cell cancer who underwent esophagectomy after definitive CRT (> or = 50
      Gy) (salvage group) and 28 patients who underwent planned esophagectomy after
      neoadjuvant CRT (30 to 45 Gy) (neoadjuvant group). RESULTS: The preoperative
      albumin level and vital capacity were significantly lower in the salvage group
      than in the neoadjuvant group. Two patients (7.4%) from the salvage group who
      underwent extended esophagectomy with three-field lymphadenectomy died of
      postoperative complications, but no deaths occurred after less-invasive surgery.
      There was no difference of overall postoperative survival between the salvage and
      neoadjuvant groups. CONCLUSIONS: The outcome of salvage esophagectomy after
      definitive CRT was similar to that of planned esophagectomy after neoadjuvant
      CRT. Less-invasive procedures might be better for salvage esophagectomy because
      of the high operative risk.

PMID- 15450832
TI  - Laparoscopic colorectal surgery in the irradiated pelvis.
AB  - BACKGROUND: Heightened interest in minimally invasive surgery and the expanding
      use of radiation therapy presents surgeons with new challenges. While
      conventional surgery in the irradiated pelvis represents a significant technical
      obstacle, indications for laparoscopic colorectal surgery are currently being
      defined. The purpose of this study is to examine the efficacy of laparoscopic
      surgery in the irradiated field. METHODS: Forty-two patients underwent
      laparoscopic colorectal surgery after preoperative radiation therapy, mean dose
      of 5,644 cGy. All patients were assessed according to intraoperative issues and
      perioperative events. RESULTS: Eleven patients underwent diverting stoma
      formation whereas 31 patients underwent resections. The overall conversion rate
      was 7% (n = 3). Average blood loss was 378 mL. There were no perioperative
      deaths. Overall morbidity was 19% (n = 8). 78% of patients tolerated clear
      liquids by postoperative day 2, and 73% tolerated a house diet by postoperative
      day 4. Average length of stay was 5.5 days. CONCLUSIONS: With proper patient
      selection and laparoscopic experience, laparoscopic colorectal surgery can be
      performed in the irradiated pelvis without undue morbidity and mortality.

PMID- 15450833
TI  - Does preoperative rofecoxib (Vioxx) decrease postoperative pain with laparoscopic
      cholecystectomy?
AB  - BACKGROUND: A prospective, randomized, double-blinded clinical trial was designed
      to study the effects of preemptive rofecoxib (Vioxx) analgesia in patients
      undergoing elective laparoscopic cholecystectomy. METHODS: One hundred-twenty
      patients were enrolled in the study over a 21-month period, and 116 completed the
      study. One half of the patients received 50 mg rofecoxib preoperatively and the
      other half, placebo. Both groups were demographically similar. Medical
      information, patient and nursing assessments, and surgical data were evaluated.
      RESULTS: A significant reduction in requirements for postoperative narcotic
      analgesic dosing was noted in the rofecoxib group. In addition, patients
      receiving rofecoxib reported significantly less nausea and improvement in their
      activity level when compared with the control group. No complications were
      encountered with the preoperative use of rofecoxib. CONCLUSIONS: We conclude that
      in patients undergoing laparoscopic cholecystectomy, preoperative administration
      of rofecoxib in selected patients may facilitate postoperative recovery and
      decrease postoperative narcotic requirements.

PMID- 15450834
TI  - Complications after Frey's procedure for chronic pancreatitis.
AB  - BACKGROUND: Frey's operation is indicated on patients with chronic pancreatitis
      who have "head dominant" disease and involves resection of the head of pancreas
      and lateral pancreaticojejunostomy (LRLPJ). There is little information about the
      postoperative complications after this procedure and the factors likely to be
      responsible for them. This paper addresses this aspect of LRLPJ. METHODS: A
      retrospective review was made of records of 41 patients undergoing LRLPJ for
      chronic pancreatitis between January 1990 to June 2003. RESULTS: Sixteen (39%)
      patients had 19 complications in the early postoperative period; septic
      complications were the commonest. One patient died. Regression analysis showed
      preoperative endoscopic pancreatic stenting to be the factor responsible for
      majority of these complications (P = 0.0041). Patients with a history of
      pancreatic stenting had a prolonged hospital stay (P = 0.022). CONCLUSIONS:
      Postoperative complications after LRLPJ are usually septic in nature and are
      likely to occur more often in patients in whom endoscopic pancreatic stenting has
      been performed before surgical intervention.

PMID- 15450835
TI  - Role of curative resection in octogenarians with malignancy.
AB  - BACKGROUND: Major resective surgery in octogenarians with malignancy is
      considered risky. Because elderly people are growing in number, there is a
      greater need to define the role of curative resection (CR) in these patients.
      METHODS: In this retrospective, consecutive review patients > or = 80 years with
      malignancy treated by surgery were included and categorized into 3 groups: group
      1 = CR group, i.e., no residual disease; group 2 = non-CR group, i.e.,
      microscopic tumor invasion of one or more resection margins; and group 3 =
      palliative surgery (PS) group. RESULTS: One hundred eighty-two patients were
      treated surgically with curative intent. Gastric and colorectal cancers were the
      most frequent (34% and 31.8%, respectively) followed by bile duct and esophageal
      cancers (15.3% and 5.5%, respectively). CR was performed in 53.3%, non-CR in
      14.8%, and palliative surgery in 31.9% of patients. Thirty-day mortality in the 3
      groups was 3.1%, 0%, and 5.2%, respectively. Mean hospital stay was similar among
      all 3 groups. In the CR group, gastric and colorectal cancers were the most
      common (41.2% and 42.2% respectively). Average survival and actuarial survival
      were significantly higher in the CR group. Disease-free survival was 645 +/- 744
      days. Five-year actuarial survival was 45.4 % in the CR group, and no patient
      survived 5 years in the other 2 groups. In the CR group, mean survival was
      significantly better in patients with good performance status and > or = 3
      supportive family members per univariate analysis. However, no significant
      difference was observed in patients with gastric and colorectal malignancy.
      Multivariate analysis revealed that TNM stage and family size affected survival
      the most. CONCLUSIONS: Gastric and colorectal cancers were most frequent among
      octogenarians reporting to our unit. CR was performed in elderly patients with
      low mortality and was associated with significantly better average and actuarial
      survival. TNM stage I to III, family size > or = 3 members, and performance
      status "0" to "1" were favorable factors.

PMID- 15450836
TI  - Role of a hyaluronic-acid derivative in preventing surgical adhesions and
      abscesses related to dropped bile and gallstones in an experimental model.
AB  - BACKGROUND: Despite its advantages, iatrogenic gallbladder perforation with
      resultant spillage of bile and gallstones is not uncommon during laparoscopic
      cholecystectomy. Although this is not generally considered a significant problem,
      spilled gallstones may cause problems even years after the operation. Hyaluronic
      acid has been introduced into clinical practice and successfully used to decrease
      postoperative adhesions after abdominopelvic surgery. In this study, we
      investigated the effectiveness of a hyaluronic-acid derivative in preventing
      complications related to spilled gallstones and bile leakage in an experimental
      study. METHODS: In 60 Wistar-Albino rats, an upper-midline abdominal incision was
      made, and the rats were divided into 5 groups (n = 12 in each group) as follows:
      group I = laparotomy alone; group II = laparotomy and intraperitoneal
      instillation of sterile bile plus gallstones; group III = laparotomy and
      instillation of infected bile and gallstones; group IV = laparotomy and
      instillation of sterile bile and gallstones plus hyaluronic acid; and group V =
      laparotomy and instillation of infected bile and gallstones plus HA. A second
      look laparotomy was performed on postoperative day 10 to assess intraperitoneal
      adhesions and abscesses. Intraperitoneal adhesions were scored, and breaking
      strengths of gallstones were measured. RESULTS: Adhesion scores were
      significantly higher in groups II and III compared with groups I, IV, and V (P <
      0.05). There was a statistically significant decrease in breaking strengths and
      adhesion scores in groups IV and V compared with groups II and III (P < 0.001).
      CONCLUSIONS: Whether infected or not, spilled gallstones and bile caused
      postoperative adhesions in this experimental model. An HA derivative
      significantly prevented postoperative adhesions and decreased breaking strengths.
      Further clinical studies are needed to validate these findings.

PMID- 15450837
TI  - Ceiling effect in technical skills of surgical residents.
AB  - BACKGROUND: Objective evaluation of technical skills is now possible. The aim of
      this study was to evaluate whether a previously validated assessment tool can
      discriminate between junior and senior higher surgical trainees (HST) with regard
      to their technical skills. METHODS: Fifteen junior trainees (years 1 to 3) and 15
      senior (years 4 to 6) were asked to perform a series of bench-model tasks, which
      included knot-tie at depth, vertical mattress suturing, sebaceous cyst excision,
      small bowel anastomosis, and saphenofemoral junction dissection. Analysis of
      performance included the Imperial College Surgical Assessment Device, which
      analyzed positional data such as total number of movements, total distance
      traveled, and time taken, and video-based qualitative evaluation of performance
      using global rating scales. In addition, all participants were asked to complete
      a self-assessment using exactly the same scoring system used by the observers.
      Statistical analysis included nonparametric tests and Cronbach's alpha was used
      for interrater reliability (IRR) A P value less than 0.05 was deemed significant.
      RESULTS: There were no significant differences in performance between junior and
      senior trainees for most of the tasks (IRR was 0.8 to 0.9). However, significant
      differences in performance were noted, in favor of the junior group, for knot-tie
      at depth, for two of the three parameters measured (total number of movements, P
      = 0.004; time taken, P = 0.01). CONCLUSIONS: In the absence of any significant
      differences between the groups, we can conclude that there is a ceiling effect
      (years 3 to 4) in performance beyond which pure technical skills, as measured by
      this tool, can no longer discriminate between levels of experience. Increasing
      the sensitivity of future assessment tools is necessary for better evaluation of
      performance levels. This finding also may imply that for the evaluation of senior
      trainees, other aspects of surgical competence should be assessed.

PMID- 15450838
TI  - Temporary abdominal closure followed by definitive abdominal wall reconstruction
      of the open abdomen.
AB  - BACKGROUND: Inability to close the abdominal wall after laparotomy for trauma may
      occur as a result of visceral edema, retroperitoneal hematoma, use of packing,
      and traumatic loss of tissue. Often life-saving, decompressive laparotomy and
      temporary abdominal closure require later restoration of anatomic continuity of
      the abdominal wall. METHODS: The trauma registry, open abdomen database, and
      patient medical records at a level 1 university-based trauma center were reviewed
      from January 1988 to December 2001. RESULTS: During the study period, more than
      15,000 trauma patients were admitted, with 88 patients (0.6%) requiring temporary
      abdominal closure (TAC). Patients ages ranged from 12 to 75 years with a mean
      injury severity score (ISS) of 28 (range 5 to 54). Forty-five patients (51%)
      suffered penetrating injuries, and 43 (49%) were victims of blunt trauma.
      Indications for TAC included visceral edema in 61 patients (70%), abdominal
      compartment syndrome in 10 patients (11%), traumatic tissue loss in 9 patients
      (10%), and wound sepsis and fascial necrosis in 8 patients (9%). Fifty-six
      patients (64%) underwent TAC at admission laparotomy, whereas 32 patients (36%)
      required TAC at reexploration. Seventy-one patients (81%) survived and 17 (19%)
      died. Of the survivors, 24 patients (34%) underwent same-admission direct fascial
      closure, and 47 patients (66%) required visceral skin grafting and readmission
      closure. Reconstructive procedures in the patients requiring skin graft excision
      included direct fascial repair (20 patients, 44%), components separation closure
      with or without subfascial tissue expansion (18 patients, 40%), pedicled or free
      tissue flaps (4 patients, 8%), and mesh repair (4 patients, 8%). One patient
      refused closure. The mean follow-up was 48 months (range 6 to 144), with an
      overall recurrence rate of 15% (range 10% to 50%), highest in the mesh repair
      group. CONCLUSIONS: Silicone sheeting TAC provides a safe and reliable temporary
      abdominal closure allowing for later definitive reconstruction. Direct fascial
      repair or components separation closure with or without tissue expansion can be
      utilized in the majority of patients for definitive reconstruction with low
      recurrence rate.

PMID- 15450839
TI  - Closure of long surgical incisions with a new formulation of 2-octylcyanoacrylate
      tissue adhesive versus commercially available methods.
AB  - BACKGROUND: Topical 2-octylcyanoacrylate tissue adhesive is an alternative to
      traditional devices for closing short surgical incisions. METHODS: An open-label,
      randomized study compared a new high-viscosity formulation of 2
      octylcyanoacrylate with commercially available devices, including low-viscosity 2
      octylcyanoacrylate, for epidermal closure of incisions > or = 4 cm requiring
      subcutaneous and/or deep-dermal suturing. RESULTS: Of patients with 1 to 3
      wounds, 106 were treated with high-viscosity 2-octylcyanoacrylate and 103 with
      commercially available devices. The day-10 rates of healing by wound were 96% and
      97% for study versus control treatment and 97% and 95% for new and old 2
      octylcyanoacrylate formulations versus other controls, respectively. Day-10
      infection rates by wound were 4 of 145 versus 7 of 131 for study versus control
      treatment and 6 of 207 and 5 of 69 for new and old 2-octylcyanoacrylate versus
      other controls, respectively. CONCLUSIONS: The new tissue adhesive formulation
      provides epidermal wound closure equivalent to commercially available devices
      with a trend to decreased incidence of wound infection.

PMID- 15450840
TI  - Temporary closure of the abdomen using a new composite prosthesis (PL-PU99).
AB  - BACKGROUND: Temporary abdominal wound closure is sometimes desirable when tension
      free approximation of the wound edges is impractical or when reexploration is
      planned. METHODS: The behavior of a composite prosthesis (PL-PU99) designed by
      our group was evaluated as a method of temporary abdominal closure in white New
      Zealand rabbits. After a 7 cm long midline laparotomy, a spindle-shaped 4 cm
      (maximum width) by 7 cm (length) fragment of PL-PU99 was sutured to the edges of
      the peritoneal, muscular, and fascial abdominal tissues, so that the biomaterial
      remained in contact with the exterior. The PL-PU99 composite is composed of a
      polypropylene mesh adhered to a sheet of polyurethane with an acrylic cement. At
      7 and 14 days after implant, animals were sacrificed and specimens taken for
      morphological, ultrastructural, morphometry of the neoperitoneum, and
      immunohistochemical (macrophage reaction, RAM-11) analysis. RESULTS: No death or
      signs of infection or rejection of the prostheses were recorded. No adhesions
      could be macroscopically observed between the composite and the intestinal loops.
      The biomaterial achieved a good seal, no leakage of fluids being detected.
      Fourteen days after implant, the neoperitoneum formed on the prosthesis was of an
      even structure and was made up of organized, vascularized connective tissue
      covered by an uninterrupted mesothelium. CONCLUSIONS: The PL-PU99 prosthesis
      shows optimal behavior at the prosthesis/visceral peritoneum interface, making it
      ideal for its use in the temporary closure of the abdomen. The implanted
      composite may also prove useful for the permanent repair of the abdominal wall.

PMID- 15450841
TI  - Video-assisted thoracoscopic decortication for management of postpneumonic
      pleural empyema.
AB  - BACKGROUND: Video-assisted thoracoscopic surgery (VATS) for decortication or
      debridement in the management of empyema thoracis has increased the available
      treatment options but requires validation. We present and evaluate our technique
      and experience with thoracoscopic management of pleural empyema, irrespective of
      chronicity. METHODS: From May 1, 2000, to April 30, 2002, VATS debridement and
      decortication in 70 consecutive patients presenting with pleural space infections
      was performed with endoscopic shaver system. A retrospective review was performed
      and the effect of this technique on perioperative outcome was assessed. RESULTS:
      The VATS evacuation of infected pleural fluid and decortication was successfully
      performed in 65 of 70 patients. The mean duration of preoperative symptoms before
      referral was 23 +/- 1.8 days. The mean duration of hospitalization before
      transfer was 13.5 +/- 1.5 days. Blood loss was 330 +/- 200 mL. Intercostal
      drainage was required for 5 +/- 3 days. The postoperative hospital stay was 5 +/-
      0.7 days. There were no operative mortalities. CONCLUSIONS: Video-assisted
      thoracoscopic decortication with endoshaver system is a simple and effective
      method in the management of the fibropurulent or organic pleural empyema.

PMID- 15450842
TI  - Emphysematous cholecystitis.

PMID- 15450843
TI  - Outcome of surgical treatment for patients with scirrhous carcinoma of the
      stomach.
AB  - BACKGROUND: Postoperative survival in patients with scirrhous gastric carcinoma
      is poorer than that in patients with other gastric carcinomas. METHODS: We
      retrospectively examined outcome in patients with scirrhous gastric carcinoma who
      underwent gastrectomy to determine how to increase postoperative survival.
      Postoperative survival in patients with scirrhous gastric carcinoma was compared
      with that in patients having other gastric cancers overall and by disease stage.
      Prognostic factors were examined for all patients including those with stage III
      disease. RESULTS: By multivariate analysis, disease stage, patient age, and
      scirrhous carcinoma were significant prognostic factors. Five-year survival in
      patients with stage III scirrhous carcinoma was significantly worse than those
      with other stage III gastric carcinomas. Extent of lymphadenectomy was one of the
      variables influencing survival in patients with stage III scirrhous carcinoma.
      CONCLUSIONS: Gastrectomy with extended lymphadenectomy should be performed to
      maximize survival in patients with stage III scirrhous gastric carcinoma.

PMID- 15450844
TI  - Juvenile gigantomastia treated by reduction mammoplasty.

PMID- 15450845
TI  - Charge sequence coding in statistical modeling of unfolded proteins.
AB  - Unfolded proteins recently attracted attention due to accumulation of
      experimental evidences for their significant role in different life processes.
      Modeling of electrostatic interactions (EI) in unfolded state of proteins is
      becoming increasingly important as well. In this paper, we stress on the
      importance of how the sequence of charged residues of a given protein is
      incorporated into the models for calculation of EI in the unfolded state. On the
      basis of the distributions of distances between titratable sites of charged
      residues calculated for polypeptide chains of various compositions, it was found
      that the distance distribution for a pair of residues, located close to each
      other along the sequence of a protein, depends on what residues constitute the
      pair in question. It was concluded that the consideration of these residue
      specific distributions is essential for a statistical model to be accurate from
      the physical point of view. It was suggested that use of distance intervals in
      the spherical model of unfolded proteins accounts better for the charge sequence
      than the set of single distance values. This was illustrated by comparison of the
      pK values of the titratable groups of the unfolded N-terminal SH3 domain of the
      Drosophila protein drk to the available experimental data.

PMID- 15450846
TI  - Stabilizing mechanisms in commercial albumin preparations: octanoate and N-acetyl
      L-tryptophanate protect human serum albumin against heat and oxidative stress.
AB  - The capability of octanoate, N-acetyl-L-tryptophanate (N-AcTrp) and other ions of
      fatty acids and amino acids to stabilize human serum albumin (HSA) against
      thermal and oxidative stress was studied. Native-PAGE showed that octanoate, and
      more hydrophobic fatty acids anions, stabilizes the monomeric form of HSA during
      heating at 60 degrees C for 30 min. Heating in the presence of octanoate did not
      change the far-UV CD-spectrum. The stabilizing role of octanoate also showed as
      an increase in denaturation temperature and calorimetric enthalpy, determined by
      differential scanning calorimetry (DSC). N-AcTrp, which was found to compete with
      octanoate for a common high-affinity site, has only a minor stabilizing effect.
      By contrast, no effect was found for l-tryptophanate or N-acetyl-L-cysteinate.
      Any ligand effect on oxidation was examined by using 2,2' -azobis(2-amidino
      propane)dihydrochloride (AAPH) as oxidizing agent. One hour of incubation
      resulted in the formation of the same number of carbonyl groups, whether
      octanoate or one of the above mentioned amino acids was present or not. However,
      the number of groups formed after 24 h of incubation was significantly decreased
      in the presence of L-tryptophanate and, especially, N-AcTrp. The effect of 1-h
      incubation with AAPH on the oxidative status of 34-Cys was studied by the HPLC
      technique. It was found that N-AcTrp, but not octanoate, has a large protecting
      effect on the sulfhydryl group. Thus, octanoate has the greatest stabilizing
      effect against heat, whereas the presence of N-AcTrp diminishes oxidation of HSA.

PMID- 15450847
TI  - On the mechanism of Rhodotorula gracilis D-amino acid oxidase: role of the active
      site serine 335.
AB  - Serine 335 at the active site of D-amino acid oxidase from the yeast Rhodotorula
      gracilis (RgDAAO) is not conserved in other DAAO sequences. To assess its role in
      catalysis, it was mutated to Gly, the residue present in mammalian DAAO, an
      enzyme with a 35-fold lower turnover number with D-alanine. The spectral and
      ligand binding properties of the S335G mutant are similar to those of wild-type
      enzyme, suggesting an active site with minimally altered electrostatic
      properties. The S335G mutant is catalytically active, excluding an essential role
      of S335 in catalysis. However, S335-OH contributes to the high efficiency of the
      mutant enzyme since the catalytic activity of the latter is lower due to a
      decreased rate of flavin reduction relative to wild-type RgDAAO. Catalytic rates
      are pH-dependent and appear to converge to very low, but finite and similar
      values at low pH for both wild-type and S335G RgDAAO. While this dependence
      exhibits two apparent pKs with wild-type RgDAAO, with the S335G mutant a single,
      apparent pK approximately 8 is observed, which is attributed to the ionization of
      the alphaNH2 group of the bound substrate. Removal of S335-OH thus suppresses an
      apparent pK approximately 6. Both wild-type RgDAAO and the S335G mutant exhibit a
      substantial deuterium solvent kinetic isotope effect (> or =4) at pH<7 that
      disappears with increasing pH and reflects a pKapp=6.9 +/- 0.4. Interestingly,
      the substitution suppresses the activity towards d-lactate, suggesting a role of
      the serine 335 in removal of the substrate alpha-OH hydrogen.

PMID- 15450848
TI  - Calorimetric determination of thermodynamic parameters of 2'-dUMP binding to
      Leishmania major dUTPase.
AB  - We have investigated the binding of 2'-deoxyuridine 5'-monophosphate (2'-dUMP) to
      Leishmania major deoxyuridine 5'-triphosphate nucleotide hydrolase (dUTPase) by
      isothermal titration microcalorimetry under different experimental conditions.
      Binding to dimeric L. major dUTPase is a non-cooperative process, with a
      stoichiometry of 1 molecule of 2'-dUMP per subunit. The utilization of buffers
      with different ionization enthalpies has allowed us to conclude that the
      formation of the 2'-dUMP-dUTPase complex, at pH 7.5 and 30 degrees C, is
      accompanied by the uptake of 0.33 +/- 0.05 protons per dUTPase subunit from the
      buffer media. Moreover, 2'-dUMP shows a moderate affinity for the enzyme, and
      binding is enthalpically driven across the temperature range studied. Besides,
      whereas DeltaG degrees remains practically invariant as a function of
      temperature, both DeltaH and DeltaS degrees decrease with increasing temperature.
      The TS and TH were 23.4 and 13.6 degrees C, respectively. The temperature
      dependence of the enthalpy change yields a heat capacity change of DeltaCp
      degrees = -618.1 +/- 126.4 cal x mol(-1) x K(-1), a value low enough to discard
      major conformational changes, in agreement with the fitting model. An
      interpretation of this value in terms of solvent-accessible surface areas is
      provided.

PMID- 15450849
TI  - Factor X activator from Vipera lebetina venom is synthesized from different
      genes.
AB  - Vipera lebetina venom contains specific coagulant Factor X activator (VLFXA) that
      cleaves the Arg52-Ile53 bond in the heavy chain of human factor X. VLFXA is a
      glycoprotein that is composed of a heavy chain (HC) and two light chains (LC)
      linked by disulfide bonds. The complete amino acid sequences of the three chains
      of the factor X activator from V. lebetina snake venom are deduced from the
      nucleotide sequences of cDNAs encoding these chains. The full-length cDNA (2347
      bp) sequence of the HC encodes an open reading frame (ORF) of 612 amino acids
      that includes signal peptide, propeptide and mature metalloproteinase with
      disintegrin-like and cysteine-rich domains. The light chain LC1 contains 123 and
      LC2 135 amino acid residues. Both light chains belong to the class of C-type
      lectin-like proteins. The N-termini of VLFXA chains and inner sequences of
      peptide fragments detected by liquid chromatography-electrospray ionization
      tandem mass spectrometry (LC MS/MS) from protein sequence are 100% identical to
      the sequences deduced from the cDNA. The molecular masses of tryptic fragments of
      VLFXA chains analyzed by matrix-assisted laser desorption ionization time of
      flight mass spectrometry (MALDI-TOF MS) also confirm the protein sequences
      deduced from the cDNAs. These are the first cloned factor X activator heavy and
      light chains. We demonstrate that the heavy and light chains are synthesized from
      different genes.

PMID- 15450850
TI  - Morphological analysis of glutaraldehyde-fixed vimentin intermediate filaments
      and assembly-intermediates by atomic force microscopy.
AB  - Atomic force microscopy (AFM) was used to study the morphology of vimentin
      intermediate filaments (IFs) and their assembly intermediates. At each time after
      initiation of IF assembly in vitro of recombinant mouse vimentin, the sample was
      fixed with 0.1% glutaraldehyde and then applied to AFM analysis. When mature
      vimentin IFs were imaged in air on mica, they appeared to have a width of
      approximately 28 nm, a height of approximately 4 nm and a length of several
      micrometers. Taking into account the probe tip's distortion effect, the exact
      width was evaluated to be approximately 25 nm, suggesting that the filaments
      flatten on the substrate rather than be cylindrical with a diameter of
      approximately 10 nm. Vimentin IFs in air clearly demonstrated approximately 21-nm
      repeating patterns along the filament axis. The three-dimensional profiles of
      vimentin IFs indicated that the characteristic patterns were presented by
      repeating segments with a convex surface. The repeating patterns close to 21 nm
      were also observed by AFM analysis in a physiological solution condition,
      suggesting that the segments along the filaments are an intrinsic substructure of
      vimentin IFs. In the course of IF assembly, assembly intermediates were analyzed
      in air. Many short filaments with a full-width and an apparent length of
      approximately 78 nm (evaluated length approximately 69 nm) were observed
      immediately after initiation of the assembly reaction. Interestingly, the short
      full-width filaments appeared to be composed of the four segments. Further
      incubation enabled the short full-width filaments to anneal longitudinally into
      longer filaments with a distinct elongation step of approximately 40 nm, which
      corresponds to the length of the two segments. To explain these observations, we
      propose a vimentin IF formation model in which vimentin dimers are supercoiling
      around the filament axis.

PMID- 15450851
TI  - Structure/function analyses of human serum paraoxonase (HuPON1) mutants designed
      from a DFPase-like homology model.
AB  - Human serum paraoxonase (HuPON1) is a calcium-dependent enzyme that hydrolyzes
      esters, including organophosphates and lactones, and exhibits anti-atherogenic
      properties. A few amino acids have been shown to be essential for the enzyme's
      arylesterase and organophosphatase activities. Until very recently, a three
      dimensional model was not available for HuPON1, so functional roles have not been
      assigned to those residues. Based on sequence-structure alignment studies, we
      have folded the amino acid sequence of HuPON1 onto the sixfold beta-propeller
      structure of squid diisopropylfluorophosphatase (DFPase). We tested the validity
      of this homology model by circular dichroism (CD) spectroscopy and site-directed
      mutagenesis. Consistent with predictions from the homology model, CD data
      indicated that the structural composition of purified HuPON1 consists mainly of
      beta-sheets. Mutants of HuPON1 were assayed for enzymatic activity against phenyl
      acetate and paraoxon. Substitution of residues predicted to be important for
      substrate binding (L69, H134, F222, and C284), calcium ion coordination (D54,
      N168, N224, and D269), and catalytic mechanism of HuPON1 (H285) led to enzyme
      inactivation. Mutants F222Y and H115W exhibited substrate-binding selectivity
      towards phenyl acetate and paraoxon, respectively. The homology model presented
      here is very similar to the recently obtained PON1 crystal structure, and has
      allowed identification of several residues within the enzyme active site.

PMID- 15450852
TI  - A proteomic approach to identify substrates of matrix metalloproteinase-14 in
      human plasma.
AB  - Matrix metalloproteinases (MMPs) are a family of zinc-containing endopeptidases
      that proteolyze extracellular matrix components as well as a variety of
      functional proteins. Here we describe a "degradomics" method that efficiently
      identifies substrates of MMP-14 in a complex protein mixture, such as plasma.
      Plasma proteins were incubated in the presence or absence of the MMP-14 catalytic
      domain and displayed on two-dimensional (2-D) gels. After a comparison of the
      gels, we selected 40 protein spots that reproducibly showed disparities. Upon in
      gel digestion, mass determination, and peptide mass fingerprinting, we identified
      15 different proteins from 31 spots. These proteins included six known substrates
      and nine potential substrates of MMP-14. Among the latter, the purified forms of
      apolipoprotein A-I, apolipoprotein E, and plasma gelsolin were cleaved in vitro
      by MMP-14, confirming that each of them is a novel substrate of MMP-14. These
      results demonstrate that our method rapidly and selectively identifies MMP-14
      substrates from human plasma proteins. This method would thus constitute a
      powerful tool for identifying the substrates of MMPs and other proteases in
      highly complex mixtures of proteins and would enhance our understanding of the
      biological roles of these enzymes.

PMID- 15450853
TI  - Structural and functional analyses of phosphoglucose isomerase from Vibrio
      vulnificus and its lysyl aminopeptidase activity.
AB  - Phosphoglucose isomerase (PGI) with a novel lysyl aminopeptidase (LysAP) activity
      was recently isolated and partially characterized from the human pathogen, Vibrio
      vulnificus. This PGI is a heterodimer consisting of 60.8- and 23.4-kDa subunits,
      which together provide LysAP activity. The present study further characterizes
      the complex structure and functions of Vibrio PGI and draws parallels with rabbit
      and human PGI. A Proscan search of Vibrio PGI revealed 194 different structural
      motifs of which 124 and 127 were also found in rabbit and human PGI,
      respectively. Vibrio PGI contains motifs for the serine, histidine and aspartic
      acid active sites of the subtilase family of serine proteases which form a
      putative catalytic triad consisting of His534 and Ser159 on the 60.8-kDa subunit
      and Asp53 on the 23.4-kDa subunit. Together, they form one LysAP site for each
      heterodimer. Each active site motif is overlapped by motifs for EF-hand calcium
      binding domains. The LysAP activity was inhibited by the addition of > or =10
      microM Ca2+, suggesting that the EF-hand calcium-binding domain may be a natural
      regulatory region for LysAP activity. In contrast, PGI's isomerase activity was
      enhanced at Ca2+ concentrations >100 microM. PGI-LysAP cleaved the amino-terminal
      lysyl residue from des-Arg10-kallidin producing des-Arg9-bradykinin; therefore,
      Vibrio PGI-LysAP may serve as a virulence factor to enhance Vibrio invasiveness.
      Together, these data provide a framework to account for PGI's LysAP activity and
      further demonstrate the structural complexity and functional importance of this
      molecule.

PMID- 15450854
TI  - Esterase catalysis of substrate vapour: enzyme activity occurs at very low
      hydration.
AB  - It has been generally accepted that enzyme activity requires a minimal hydration
      of about 0.2 g H2O g(-1) protein. This fits well with evidence that hydration
      above this level is associated with the onset of intramolecular motions. The
      influence of enzyme hydration on the hydrolysis of substrate by Candida rugosa
      Lipase B and pig liver esterase was investigated. Each enzyme was studied as a
      powder at various hydration levels, using vapour phase ethyl butyrate as
      substrate. This procedure allows the separation of those effects that are due to
      hydration from those arising from diffusional constraints. We found hydrolytic
      activity in both enzymes at all hydration levels above zero (between 0.054-0.47
      and 0.029-0.60 g H2O g(-1) protein, respectively) that were investigated. The
      lowest hydration level investigated, <0.03 g H2O g(-1) enzyme, corresponded to a
      water/enzyme mole ratio of 100 and a coverage of about 10% of the enzyme surface
      by water molecules. The hydrolytic activity of both enzymes was dependent on
      protein hydration. However, since the hydrolysis of ethyl butyrate requires water
      as a second substrate, the absence of activity at zero hydration does not rule
      out the possibility of enzyme activity in the absence of water. These results
      suggest that the properties conferred on proteins by water, at least above 10%
      surface coverage (in this case corresponding to a hydration level of 0.03 g H2O
      g(-1) protein), are not a requirement for enzyme catalysis.

PMID- 15450855
TI  - Comparative proteomics and subtyping of venom phospholipases A2 and disintegrins
      of Protobothrops pit vipers.
AB  - To explore the venom diversity and systematics of pit vipers under the genus
      Protobothrops, the venom phospholipases A2 (PLA2s) of P. mangshanensis, P.
      elegans and P. tokarensis were purified and characterized for the first time. The
      results were compared with the corresponding venom data of other co-generic
      species including P. mucrosquamatus, P. flavoviridis and P. jerdonii. Based on
      sequence features at the N-terminal regions, we identified five PLA2 subtypes,
      i.e., the Asp49-PLA2s with N6, E6 or R6 substitution and the Lys49-PLA2. However,
      not all subtypes were expressed in each of the species. Venom N6-PLA2s from P.
      mangshanensis and P. tokarensis venom were weakly neurotoxic toward chick
      biventer cervicis tissue preparations. The venoms of P. tokarensis and P.
      flavoviridis contained identical PLA2 isoforms. In most Protobothrop
      disintegrins, sequences flanking the RGD-motif are conserved. Phylogenetic
      analyses based on amino acid sequences of both families of the acidic PLA2s and
      the disintegrins clarify that these species could belong to a monophyletic group.

PMID- 15450856
TI  - Crystallization and preliminary X-ray crystallographic analysis of strictosidine
      synthase from Rauvolfia: the first member of a novel enzyme family.
AB  - Strictosidine synthase is a central enzyme involved in the biosynthesis of almost
      all plant monoterpenoid indole alkaloids. Strictosidine synthase from Rauvolfia
      serpentina was heterologously expressed in Escherichia coli. Crystals of the
      purified recombinant enzyme have been obtained by the hanging-drop technique at
      303 K with potassium sodium tartrate tetrahydrate as precipitant. The crystals
      belong to the space group R3 with cell dimensions of a=b=150.3 A and c=122.4 A.
      Under cryoconditions (120 K), the crystals diffract to about 2.95 A.

PMID- 15450857
TI  - Crystallization and preliminary X-ray diffraction studies of the metal-ion
      mediated ternary complex of the HutP protein with L-histidine and its cognate
      RNA.
AB  - HutP is an RNA-binding protein that regulates the expression of the Bacillus
      subtilis hut operon by binding to cis-acting regulatory sequences within hut
      mRNA, exclusively in the presence of L-histidine. We recently solved the crystal
      structure of a binary complex (HutP with an L-histidine analog) that revealed a
      novel RNA-binding fold, and identified the important residues that interact with
      the L-histidine analog. In addition, we have defined the minimal RNA binding
      segment that is required for HutP recognition. Interestingly, we showed that
      ternary complex formation depends on the availability of not only L-histidine but
      also divalent metal ions. Here we report the crystallization and preliminary X
      ray diffraction analysis of the HutP ternary complex. The ternary complex was
      crystallized in the presence of Mg2+ along with L-histidine and hut mRNA, using
      the hanging drop vapor diffusion method. The crystal belongs to the R3 space
      group, with unit cell parameters a=b=75.30 A, c=133.8 A. A complete data set at
      1.60 A was collected.

PMID- 15450858
TI  - Effects of superoxide dismutase and polyclonal tumor necrosis factor-alpha
      antibodies on chloroacetate-induced cellular death and superoxide anion
      production by J774.A1 macrophages.
AB  - Dichloroacetate (DCA) and trichloroacetate (TCA) are by-products that are formed
      during the process of water chlorination and have been previously shown to induce
      superoxide anion (SA) production and cellular death when added to J774.A1
      macrophage cultures. In this study, the effects of superoxide dismutase (SOD) and
      polyclonal tumor necrosis factor-alpha (TNF-alpha) antibodies on DCA- and TCA
      induced SA production and cellular death have been tested on the J774.A1
      macrophage cultures. TCA and DCA were added to different cultures either alone,
      each at a concentration of 16 mM, or in combination with SOD (2-12 units/ml), or
      with TNF-alpha antibodies (10 and 25 units/ml). Cells were incubated for 48 h,
      after which cellular death/viability, lactate dehydrognase (LDH) leakage by the
      cells, and SA production by the cells were determined. While TCA and DCA caused
      significant cellular toxicity, indicated by reduction in cellular viability and
      increases in LDH leakage and SA production, SOD addition resulted in significant
      reduction of the effects induced by the compounds. On the other hand, addition of
      TNF-alpha antibodies to the DCA- and TCA-treated cultures resulted in significant
      reduction of DCA- but not TCA-induced cellular death and SA production by the
      cells. Although these results suggest a significant role for SA in DCA- and TCA
      induced cellular death, they may also suggest two different mechanisms for the
      chloroacetate-induced SA production by the cells.

PMID- 15450859
TI  - Evaluation of biomarkers in oyster larvae in natural and polluted conditions.
AB  - Crassostrea gigas D-shaped larvae were subjected to different conditions of
      temperature and salinity for 24 h and four biomarkers (acetylcholinesterase
      (AChE) activity, thiobarbituric acid reactive substances (TBARS) levels,
      glutathione S-transferase (GST) and catalase (CAT) activities) were measured.
      AChE activity decreased when salinity increased from 25 to 30 and 35 psu at 20
      and 25 degrees C. Temperature did not seem to have an influence on AChE activity.
      TBARS levels increased as a function of salinity when the temperature was
      maintained at 20 degrees C, whereas at 25 degrees C no effect of salinity could
      be observed. Variations in GST and CAT activities were not significant with
      salinity and temperature except that catalase activity was higher at 25 degrees C
      than at 20 degrees C. Exposure experiments were conducted at 23 degrees C and 30
      psu with carbofuran (100 and 1000 microg/l) and malathion (100 and 300 microg/l).
      There was an inhibition of AChE activity with carbofuran, and a toxic effect
      shown by an increase in TBARS levels counteracted by increases in GST and CAT
      activities which protected the larvae. When two pairs of adults producing larvae
      were taken into consideration, significant differences in biomarker levels were
      noted between the larval offspring of each pair. Malathion induced a decrease in
      AChE activity and an increase in CAT activity.

PMID- 15450860
TI  - PAH biotransformation in terrestrial invertebrates--a new phase II metabolite in
      isopods and springtails.
AB  - Soil-living invertebrates are exposed to high concentrations of contaminants
      accumulating in dead organic matter, such as polycyclic aromatic hydrocarbons
      (PAHs). The capacity for PAH biotransformation is not equally developed in all
      invertebrates. In this paper, we compare three species of invertebrates,
      Porcellio scaber (Isopoda), Eisenia andrei (Lumbricidae) and Folsomia candida
      (Collembola), for the metabolites formed upon exposure to pyrene. Metabolic
      products of pyrene biotransformation in extracts from whole animals or isopod
      hepatopancreas were compared to those found in fish bile (flounder and plaice).
      An optimized HPLC method was used with fluorescence detection;
      excitation/emission spectra were compared to reference samples of 1-hydroxypyrene
      and enzymatically synthesized conjugates. Enzymatic hydrolysis after
      fractionation was used to demonstrate that the conjugates originated from 1
      hydroxypyrene. All three invertebrates were able to oxidize pyrene to 1
      hydroxypyrene, however, isopods and collembolans stood out as more efficient
      metabolizers compared to earthworms. In contrast to fish, none of the
      invertebrates produced pyrene-1-glucuronide as a phase II conjugate. Both
      Collembola and Isopoda produced significant amounts of pyrene-1-glucoside,
      whereas isopods also produced pyrene-1-sulfate. A third, previously unknown,
      conjugate was found in both isopods and springtails, and was analysed further
      using electrospray and atmospheric pressure chemical ionisation mass
      spectrometry. Based on the obtained mass spectra, a new conjugate is proposed:
      pyrene-1-O-(6"-O-malonyl)glucoside. The use of glucose-malonate as a conjugant in
      animal phase II biotransformation has not been described before, but is
      understandable in the microenvironment of soil-living invertebrates. In the
      earthworm, three other pyrene metabolites were observed, none of which was shared
      with the arthropods, although two were conjugates of 1-hydroxypyrene. Our study
      illustrates the great variety of the still unexplored metabolic diversity of
      invertebrate xenobiotic metabolism.

PMID- 15450861
TI  - Bacterial infection and tissue-specific Hsp72, -73 and -90 expression in western
      painted turtles.
AB  - Heat shock proteins (Hsps) are molecular chaperones that assist intracellular
      folding, assembly and translocation of proteins in prokaryotic and eukaryotic
      cells. A variety of stresses including hyperthermia, radiation, heavy metals,
      ischemia, anoxia and reoxygenation have been shown to increase the expression of
      Hsps. Likewise, bacterial infection represents a stress for the host cell. In
      this study, expression of the constitutive (Hsp73) and inducible (Hsp72) isoforms
      of Hsp70 and Hsp90 was monitored in brain, heart, liver and skeletal muscle from
      the western painted turtle Chrysemys picta bellii diagnosed with Septicemic
      Cutaneous Ulcerative Dermatitis (SCUD). This disease is caused by a gram-negative
      bacterium probably belonging to the Citrobacter spp. The expression of Hsp73
      increased 1.8-fold in brain and liver, 2.2-fold in heart but did not change in
      skeletal muscle; Hsp72 expression increased 5.5-fold in brain and 3-fold in liver
      but did not change in heart or skeletal muscle; Hsp90 expression increased 9-fold
      in brain, 2.7-fold in heart and 2.4-fold in skeletal muscle but did not change in
      liver. These results suggest a tissue-specific Hsp response during bacterial
      infection and a role for Hsps in immunopathological events in reptiles.

PMID- 15450862
TI  - Production in vitro of toxic macromolecules by strains of Beauveria bassiana, and
      purification of a chitosanase-like protein secreted by a melanizing isolate.
AB  - The production of macromolecular insecticidal toxins in Adamek's medium by two
      selected strains of Beauveria bassiana was investigated. Filtrates and dialysates
      of the melanizing strain 618 were toxic when injected into the lepidopteran
      insect Galleria mellonella. Separation by DEAE chromatography revealed that peaks
      eluted respectively with 100 and 200 mM NaCl (P 100 and P 200) had an
      insecticidal activity and induced cuticular blackening. A hydrophilic protein,
      Bclp, which causes the formation of brownish spots of the integument, was
      purified from P 200 by means of chromatographic and electrophoretic methods. Bclp
      exhibited clear sequence homologies with fungal chitosanases of Fusarium solani.
      It has a molecular mass of 28 kDa, a pHI of 4 and is thermolabile. Injection of
      Bclp causes the same cytoxic effects and alterations of the cuticule as those
      observed during mycosis, and may contribute to the virulence of strain 618.
      Comparatively, the most obvious characteristic of the weakly melanizing strain
      101 is the lack of significant toxic activity of its P 200, which does not
      contain Bclp. However, this strain secretes other insecticidal molecules active
      on lepidopterans, presently unidentified.

PMID- 15450863
TI  - Decreased apoptosis in the forebrain of adult male medaka (Oryzias latipes) after
      aqueous exposure to ethinylestradiol.
AB  - Endocrine disrupting compounds (EDCs), especially those that are estrogenic, are
      an issue of growing concern because they may ultimately adversely affect wildlife
      survival. 17-beta-Estradiol and its synthetic counterpart, 17-alpha
      ethinylestradiol, two common EDCs, are associated with intersex conditions and
      impaired male reproductive behavior in fish. Male and female Japanese medaka
      (Oryzias latipes) were exposed to 10 ng/l ethinylestradiol for 6 months. Using
      terminal dideoxynucleotidyl-mediated dUTP nick end-labeling (TUNEL) to quantitate
      cell death, we found that ethinylestradiol-exposed males had significantly fewer
      apoptotic cells in the forebrain compared to untreated males and exposed females.
      Our results show that the effects of ethinylestradiol exposure are highly
      variable among individuals of the same species and even within tissues of the
      same individual. Thus, when examining the effects of EDCs on natural populations,
      data from a variety of tissues should be examined and the interpretation of any
      effects should include consideration of tissue-specific processes.

PMID- 15450864
TI  - Early postnatal effects of prenatal exposure to glucocorticoids on testosterone
      metabolism and biogenic monoamines in discrete neuroendocrine regions of the rat
      brain.
AB  - We investigated the effects of hydrocortisone acetate and dexamethasone
      administered to pregnant rats during the last gestational week on sexual
      differentiation of testosterone metabolism and biogenic monoamine contents and
      turnover in the discrete brain regions in 10-day-old offspring. In the preoptic
      area, sex-dependent differences in aromatase activity were attenuated by prenatal
      glucocorticoids. Prenatal dexamethasone but not hydrocortisone acetate caused the
      inversion of sexual dimorphism of 5alpha-reductase activity in the preoptic area.
      In the brain preoptic area of the male pups prenatally exposed to hydrocortisone
      acetate, a decrease in noradrenaline turnover was found. Dopamine turnover in the
      preoptic area and 5-hydroxytryptamine metabolism in the preoptic area and medial
      basal hypothalamus increased in females as a result of hydrocortisone acetate
      treatment. Our results indicate that excess glucocorticoids in prenatal life
      modifies the basic neurochemical and neurophysiological mechanisms of sexual
      brain differentiation and might contribute to behavioral and reproductive
      disorders in adulthood.

PMID- 15450865
TI  - Estradiol-17beta and dihydrotestosterone differentially regulate vitellogenin and
      insulin-like growth factor-I production in primary hepatocytes of the tilapia
      Oreochromis mossambicus.
AB  - Effects of estradiol-17beta (E2) and 5alpha-dihydrotestosterone (DHT) on the
      production of vitellogenin (Vg), insulin-like growth factor-I (IGF-I) and IGF
      binding proteins (IGFBPs) were examined in vitro using primary hepatocyte culture
      of the tilapia. Estradiol produced a significant and concentration-related
      stimulation of Vg release and concomitant, concentration-related reduction in IGF
      I mRNA expression in both male and female hepatocytes. In male hepatocytes, DHT
      significantly increased IGF-I expression, whereas DHT inhibited IGF-I expression
      and stimulated Vg release in female hepatocytes. Estradiol treatment
      significantly reduced the release of 25 kDa IGFBP, while stimulating the release
      of 30 kDa IGFBP from male hepatocytes. In female hepatocytes, E2 significantly
      increased both 25 and 30 kDa IGFBPs. In male hepatocytes, DHT significantly
      reduced 25 kDa IGFBP without affecting 30 kDa IGFBP. Conversely, DHT treatment of
      hepatocytes from female fish significantly increased both the 25 and 30 kDa
      IGFBPs. The different growth rates observed between male and female tilapia may
      be a result of gonadal steroid hormones eliciting direct and antagonistic effects
      on production of IGF-I (growth) and Vg (reproduction) in the liver. Indeed, the
      different growth patterns likely result from a difference in the sensitivity of
      male and female hepatocytes to gonadal steroid hormones. These results also
      indicate direct effects of gonadal steroid hormones on production of IGFBPs,
      which may play a role in regulating IGF-I mediated growth.

PMID- 15450866
TI  - Heavy metals in tissues of loggerhead turtles (Caretta caretta) from the
      northwestern Adriatic Sea.
AB  - Thirty-five specimens of Caretta caretta were collected dead along the Adriatic
      Sea coast from the Po Delta to the Reno mouth (Italy). Turtles were classified
      into four size categories ranging from 24.5 to 74 cm, by measuring the minimum
      straight-line carapace length (MSCL). Cd, Cu, Fe, Mn, Ni, and Zn levels were
      assessed in liver, lung, muscle and adipose tissue. Cd, Cu and Fe mainly
      accumulated in the liver (8.9, 23.7 and 1180 mg/kg dry mass [d.w.],
      respectively), and Mn in the lung (29.5 mg/kg d.w.). Levels of Ni were higher in
      adipose (22 mg/kg d.w.) than other tissues, while Zn concentrations were higher
      in muscle (about 140 mg/kg d.w.). Negative correlations with size were
      established for Zn in liver and Cu in adipose tissue, while positive correlations
      were observed for Mn and Ni in adipose tissue. Metal concentrations did not
      differ between males and females, nor between individuals found stranded and
      those victims of by-catch. On average, Cd, Cu, Mn and Ni concentrations in our
      specimens were higher than in loggerhead turtles and other species living in
      other areas. We hypothesize that trace metals could be used as "acquired markers"
      to help investigate migration routes of C. caretta.

PMID- 15450867
TI  - Liver biotransforming enzymes in woodrats Neotoma stephensi (Muridae).
AB  - Mammalian herbivores are exposed to extremely high levels of plant secondary
      compounds naturally present in their diet. It has been speculated that specialist
      herbivores should express a unique pattern of biotransforming enzymes to permit
      the consumption of a single species of toxic plant. Specifically, specialists
      should rely on pathways that effectively biotransform the toxins they routinely
      encounter in their diet. We examined the hepatic mRNA expression and activity or
      content of biotransforming enzymes in the specialist herbivorous woodrat, Neotoma
      stephensi, and compared results to those of laboratory rats (Sprague-Dawley
      strain Rattus norvegicus). In addition, we investigated the role of alpha-pinene,
      a specific plant toxin present in the diet of N. stephensi on the mRNA expression
      pattern and activity or content of biotransforming enzymes in Sprague-Dawley
      rats. Overall, the levels of functionalization enzyme activity and mRNA were
      found to be higher in specialists, while glucuronidation enzyme activity and mRNA
      were lower. These results support predictions that specialist herbivores rely
      more on functionalization biotransformation pathways rather than glucuronidation
      pathways.

PMID- 15450868
TI  - PCB impairs smoltification and seawater performance in anadromous Arctic charr
      (Salvelinus alpinus).
AB  - The impacts of polychlorinated biphenyl (PCB) exposure on smoltification and
      subsequent seawater performance were investigated in hatchery-reared, anadromous
      Arctic charr (Salvelinus alpinus). The fish were subjected to a 2-month summer
      seawater residence, after which they were orally dosed with 0 (Control, C), 1
      (Low Dose, LD) or 100 mg Aroclor 1254 kg(-1) body mass (High Dose, HD) in
      November. They were then held in fresh water, without being fed (to mimic their
      natural overwintering in freshwater), until they had smolted in June the next
      year. The smolts were then transferred to seawater and fed to mimic their summer
      feeding residence in seawater, followed by a period without food in freshwater
      from August until maturation in October. Compared with C and LD charr, the HD
      charr had either a transient or a permanent reduction in plasma growth hormone,
      insulin-like growth factor-1, and thyroxin and triiodothyronine titers during the
      period of smoltification. These hormonal alterations in the HD charr corresponded
      with impaired hyposmoregulatory ability in May and June, as well as reduced
      growth rate and survival after transference to seawater. Consequently, fewer fish
      in the HD group matured in October compared to the other two treatments. The HD
      fish had a liver PCB concentration ranging between 14 and 42 mg kg(-1) wet mass,
      whereas there were similar, and very low, liver PCB concentrations in LD and C
      fish throughout the smolting period. Our findings suggest that PCB might
      compromise mechanisms important for fitness in a fish species living in an
      extreme environment.

PMID- 15450869
TI  - An antagonistic 5-HT receptor system in the auricles of the systemic heart
      complex of Sepia officinalis L. (Cephalopoda) shows 5-HT1 and 5-HT4 subtype
      properties.
AB  - In pharmacological bioassays on isolated ring-shaped auricle preparations of
      Sepia officinalis, the action of the specific 5-hydroxytryptamine (5-HT) agonists
      8-OH-DPAT (5-HT1a), CP-93129 (5-HT1b), TFMPP (5-HT1b) and RS-67333 (5-HT4) on
      these autonomously contractile compartments was studied. 8-OH-DPAT and CP-93129
      induced mainly positive effects on frequency and tone on the isotonically
      suspended auricles. The positive effect of 8-OH-DPAT on frequency was blocked by
      the specific 5-HT1a antagonist NAN-190. The 5-HT1b agonist TFMPP caused similar
      effects on tone and a positive impact on the auricular amplitude. The highly
      specific 5-HT4 agonist RS-67333 induced an effect opposite to the action of 5-HT1
      agonists inducing mainly negative effects on frequency, amplitude and tone,
      causing a diastolic standstill at a concentration of 10(-6) M. These negative
      effects were blocked by the adenylyl cyclase inhibitor SQ-22,536 in the absence
      of a diastolic standstill. The opposing action of 5-HT1 and 5-HT4 agonists on
      auricular contractile activity suggests that an antagonistic 5-HT-receptor system
      exists within the auricular myocardial cells of S. officinalis, probably
      consisting of 5-HT1- and 5-HT4-like subtypes. The results also suggest that
      adenylyl cyclase acts as the intracellular target enzyme of both signal
      transduction mechanisms.

PMID- 15450870
TI  - Multiple biomarker response in rainbow trout during exposure to hexavalent
      chromium.
AB  - This research investigated hexavalent chromium toxicity in rainbow trout using a
      panel of biomarkers at different levels of biological organization. A time-course
      experiment in which rainbow trout were exposed in hard water (63.5 mg/L CaCO3) to
      a sublethal concentration of hexavalent chromium (10 mg/L) for a period of 28
      days was conducted. The responses of multiple biomarkers were measured in gill
      and liver tissues at varying time points. Significant differences in
      metallothionein induction, superoxide dismutase activity, lipid peroxidation,
      cellular morphology, and growth were observed. Results indicated that gill
      tissues were more sensitive than hepatic tissues to chromium toxicity, yet
      hepatic tissues appeared to play a larger role in the organism's adaptive
      response to chromium compared to gill tissues. This study highlights the
      importance of using a set of integrated biomarkers to assess contaminant exposure
      and effects.

PMID- 15450871
TI  - Metastatic spine disease: epidemiology, pathophysiology, and evaluation of
      patients.
AB  - Spinal metastasis is the most commonly en-countered tumor of the spine and
      represents an ominous extension of neoplastic disease. Symptomatic spinal
      metastases produce a characteristic clinical syndrome beginning with local back
      or neck pain. All too often, the significance of presenting pain is not
      appreciated and correct diagnosis is delayed until more blatant manifestations of
      spinal cord or nerve root dysfunction are manifest. Pain is followed by
      weakness,numbness, and sphincter dysfunction. The natural history is one of
      relentless progression to complete and irreversible paralysis unless timely
      treatment is undertaken. Plain radiographs provide a simple and useful screening
      test. MRI is, however, the imaging method of choice, providing information
      concern-ing the level, location, and geometry of the spinal tumor as well as
      details concerning the bony integrity of the spine, particularly adjacent to a
      culpable tumor, all of which is essential to determine the management options and
      treatment strategies. Percutaneous image-guided biopsy is a useful test to
      establish a tissue diagnosis.

PMID- 15450872
TI  - Biomechanics of metastatic spine cancer.
AB  - The spine is the most common site of skeletal metastases. Most of these occur
      within the vertebral body, thereby predisposing patients to pathologic fracture.
      The risk of fracture is related to the extent of bony destruction, location of
      the lesion, and inherent bone quality. The regional variation in spine anatomy
      exposes the cervical,thoracic, and lumbar spines to different forces,resulting in
      varying fracture types.

PMID- 15450873
TI  - Radiology of metastatic spine cancer.
AB  - Radiologic imaging is an essential component of current spinal cancer diagnosis
      and treatment algorithms and is used for cancer diagnosis,determination of tumor
      extent for treatment planning, and subsequent assessment of therapy efficacy on
      follow-up.

PMID- 15450874
TI  - Embolization of metastatic spinal tumors.
AB  - Embolization is a safe and valuable primary and adjunctive treatment option for
      metastatic spinal tumors. Close consultation between the neurosurgeon, the
      oncologist, the radiation oncologist, and the interventionalist should lead to
      more applications of embolization techniques,thereby enhancing the treatment of
      metastatic spinal lesions. The development of newer embolic agents with
      chemotherapeutic properties should add to the efficacy of embolization for
      metastatic spinal disease.

PMID- 15450875
TI  - Evolution of treatment for metastatic spine disease.
AB  - The management of patients with metastatic disease of the spine should be highly
      individualized and depends on several factors, including the clinical
      presentation, duration of symptoms, tu-mor type, anticipated radiosensitivity,
      tumor lo-cation, extent of extraspinal disease, integrity of the spinal column,
      and medical fitness and life expectancy of the patient. Early diagnosis and
      intervention are of paramount importance in improving the likelihood of
      functional neurologic recovery, with the maintenance of ambulation as the primary
      goal. Effective management of axial spinal pain involves reconstruction and
      stabilization of the spinal column. Although the ideal therapy has not been
      established, a wide range of management options is currently available.

PMID- 15450876
TI  - Surgical management of cervical spinal metastasis: anterior reconstruction and
      stabilization techniques.
AB  - Anterior cervical corpectomy followed by reconstruction and stabilization is an
      effective strategy in the management of spinal metastasis in some patients.
      Various techniques are available in the armamentarium of the spine tumor surgeon.
      In patients with a limited life expectancy,reconstruction with PMMA achieves
      immediate stability and thus obviates the need for an external orthosis and
      allows for early mobilization. The addition of anterior cervical plate fixation
      provides extra support to prevent distraction failure. In some cases, posterior
      stabilization may be necessary to achieve adequate stability.

PMID- 15450877
TI  - Posterior surgical approaches and outcomes in metastatic spine-disease.
AB  - Spinal cord compression represents a major cause of morbidity and suffering in
      cancer patients. Surgery should be considered a form of primary therapy in many
      of these patients. The goals of surgery and the approach used are functions of a
      number of variables, including the surgeon's preference, the location of disease
      within the spine (cervical, thoracic, or lumbar),the extent of disease within
      each vertebra, the number of levels affected, and the patient's medical health
      and overall prognosis. Currently,the goals of any major debulking surgery are to
      decompress the spinal cord, prevent local recurrence, reconstruct the spine, and
      provide immediate stabilization with the use of fixation devices. Posterior
      approaches, starting with the decompressive laminectomy, have traditionally been
      the most common surgical procedures for metastatic spine disease. The laminectomy
      should only be used for disease isolated to the dorsal spine without evidence of
      concomitant instability. A laminectomy combined with instrumentation has been
      shown to provide superior results but should be reserved for those patients who
      cannot tolerate or would not benefit from more aggressive surgery. Various
      posterolateral approaches have been devised to access more ventrally placed
      lesions. These include the transpedicular approach, the costotransversectomy, and
      the lateral extracavitary/parascapular approach. Each of these allows adequate
      spinal cord decompression anteriorly and posteriorly and the ability to
      reconstruct and stabilize with acceptable peri-operative risk. It must be
      remembered that surgery for this disease is almost always palliative.Thus,
      surgery should be a means to maximize the patient's quality of life while
      minimizing the risk of suffering surgical complications.

PMID- 15450878
TI  - The lateral extracavitary approach to the thoracic and lumbar spine.
AB  - The LECA is a technically challenging procedure with a steep learning curve. It
      is one of the most versatile approaches to the spine, however,with a logical
      sequence of maneuvers that can be combined to adapt the LECA for many different
      spinal procedures that need to be performed for decompression of the spinal cord
      and reconstruction of the spinal column in cancer patients.

PMID- 15450879
TI  - Anterior approaches for thoracolumbar metastatic spine tumors.
AB  - The management of patients with metastatic disease of the thoracolumbar spine
      should be highly individualized and depends on several factors, including the
      clinical presentation, duration of symptoms, tumor type, anticipated radio
      sensitivity, tumor location, extent of extraspinal disease, integrity of the
      spinal column, and medical fitness and life expectancy of the patient. Although
      no single approach is always applicable, anterior approaches provide several
      advantages, including minimal removal of uninvolved bone, rapid extirpation of
      the tumor, improved hemostasis, effective reconstruction of the weight-bearing
      anterior column, short-segment fixation,and improved wound healing. Wider
      acceptance and judicious use of current surgical techniques for metastatic spine
      disease may improve the quality of life of patients too often denied such
      treatment.

PMID- 15450880
TI  - Metastatic sacral tumors.
AB  - Therapeutic approaches are still a matter of debate. Given the complexity of the
      sacral anatomy and the vicinity of major neural structures and vital organs,
      advantages of radical resection for local disease control must be weighed against
      the anticipated treatment morbidities and complications. It becomes imperative to
      establish a multidisciplinary team approach to provide the best environment for
      establishing individualized management plans.

PMID- 15450881
TI  - Minimally invasive treatments for metastatic tumors of the spine.
AB  - Minimally invasive approaches are finding their way into all aspects of
      metastatic spinal disease from diagnosis to treatment of patients who are
      diagnosed early in their course as well as patients with multifocal metastases.
      For patients who are found to have asymptomatic spinal metastases, diagnosis is
      important to guide management and treatment so as to prevent future morbidity.
      These patients also now have the option of less invasive techniques for
      resection,reconstruction, and stabilization, including endoscopy and less
      invasive surgical approaches. Patients who are treated later in their course,
      with multifocal metastatic disease also have more options for palliation of pain
      and for stability,including vertebroplasty/kyphoplasty and radio-frequency tumor
      ablation as well as some of the percutaneous methods of stabilization described
      previously. As techniques evolve and im-prove, patients will continue to have
      more access to less invasive options for treatment of spinal metastases.

PMID- 15450882
TI  - Basic principles of radiobiology, radiotherapy, and radiosurgery.
AB  - This article reviews the basic principles of radiobiology and the application
      thereof to the treatment of metastatic spine tumors. The most important concepts
      of dose fractionation and the concept of biologically effective dose as well as
      spinal cord tolerance to single and multiple doses of radiotherapy are
      emphasized. Basic principles of treatment planning for radiotherapy and
      radiosurgery are outlined.

PMID- 15450883
TI  - Radiation and intensity-modulated radiotherapy for metastatic spine tumors.
AB  - Although promising, many questions remain regarding spinal IMRT. The challenge of
      patient immobilization must be surmounted before a radiation facility can safely
      offer spinal IMRT. At many institutions, the increased expense and time
      requirements from physicists, therapists, and physicians preclude the routine use
      of IMRT for spinal lesions. Finally, there are no randomized data comparing the
      safety or efficacy of IMRTwith more conventional means of spinal radiation.
      Nonetheless, IMRT is one of the most important recent technologic advancements in
      radiation therapy. For complex treatment problems, such as spinal tumors, in
      which the surrounding organs at risk traditionally place significant constraints
      on the prescription dose, IMRT has great potential to provide the ideal solution.

PMID- 15450884
TI  - Cyberknife radiosurgery for metastatic spine tumors.
AB  - Metastatic spine tumors affect a large number of patients each year, resulting in
      significant pain,destruction of the spinal column causing mechanical instability,
      and neurologic deficits. Standard therapeutic options include surgery and
      fractionated external beam radiotherapy. The first option can be associated with
      significant morbidity and limited local tumor control. Conversely, radiotherapy
      may provide less than optimal pain relief and tumor control, because the total
      dose is limited by the tolerance of adjacent tissues, such as the spinal cord.
      The emerging technique of spinal radiosurgery represents a logical extension of
      the current state-of-the-art radiation therapy. It has the potential to
      significantly improve local control of cancer of the spine, which could translate
      into more effective palliation and potentially longer survival. Spinal
      radiosurgery might offer improved pain control and a longer duration of pain
      control by giving larger radiobiologic doses.This technique also allows for the
      treatment of lesions previously irradiated using external beam radiation. Another
      advantage to the patient is that irradiation can be completed in a single day
      rather than several weeks, which is not inconsequential for patients with a
      limited life expectancy. In addition, cancer patients may have difficulty with
      access to a radiation treatment facility for prolonged daily fractionated
      therapy. This technique allows for the treatment of lesions previously irradiated
      using external beam radiation.Finally, the procedure is minimally invasive
      compared with open surgical techniques and can be performed in an outpatient
      setting. Similar to intracranial radiosurgery, stereo-tactic radiosurgery now has
      a feasible and safe delivery system available for the treatment of spinal
      metastatic lesions. The major potential benefit of radiosurgical ablation of
      spinal lesions is a relatively short treatment time in an outpatient setting
      combined with potentially better local control of the tumor with minimal risk of
      side effects. CyberKnife spinal radiosurgery offers a new and important
      alternative therapeutic modality for the treatment of spinal metastases in
      medically inoperable patients, previously irradiated sites, and for lesions not
      amenable to open surgical techniques or as an adjunct to surgery. Spinal
      radiosurgery is likely to become an essential part of any neurosurgical spine
      center that treats a large number of patients with spinal metastases.

PMID- 15450885
TI  - Novalis radiosurgery for metastatic spine tumors.
AB  - It is logical to anticipate that the field of spinal radiosurgery will evolve in
      a fashion similar to that seen for intracranial radiosurgery. Given the frequency
      of various pathologic entities that affect the spine, including those that have
      proven to be largely intractable to surgery, radiation, and chemotherapy (eg,
      sarcomas), and the serious clinical, economic and quality-of-life consequences of
      paraplegia, radiosurgery offers new hope as an adjuvant or primary therapy. The
      meticulous application of well-designed investigations of relevant clinical
      outcomes will be critical to the appropriate and effective use of this
      technology.

PMID- 15450886
TI  - Management of pain associated with spinal tumor.
AB  - Metastatic spinal disease is common in cancer patients, and it is a frequent
      source of pain and disability. Expert management of the patient's pain and
      neurologic dysfunction is required. Neurosurgical advances have afforded the
      patient the opportunity to have improved symptom management and improved quality
      of-life outcomes. Patients and their families are best served by the provision of
      supportive care by specialty pain medicine and palliative care services
      (especially neurology based) working with the primary neurosurgical team in an
      integrated model.

PMID- 15450887
TI  - Medical management of skeletal metastasis.
AB  - This article discusses general principles of medical management of bone
      metastases, including diagnosis and follow-up; management of specific symptoms;
      options for systemic treatment, including bisphosphonates; specific details about
      each cancer type; and future directions in therapy.

PMID- 15450888
TI  - Neuromonitoring during surgery for metastatic tumors to the spine: intraoperative
      interpretation and management strategies.
AB  - Resection of metastatic tumors of the spine poses great technical challenges,
      with the potential of creating severe neurologic deficits. Several modalities of
      electrophysiologic monitoring, including SSEPs and MEPs, have evolved to aid in
      resection of these tumors. This review has presented additional techniques-such
      as mapping of the dorsal columns with antidromic-elicited SSEPs to plan the
      myelotomy and direct intra-medullary stimulation-that help to identify the extent
      of the tumor margin at its interface with functional tracts. Neuromonitoring can
      potentially minimize the sensory and motor damage that can occur during resection
      of metastatic tumors of the spine. Further experience with these techniques
      should allow improved results follow-ing surgical procedures in functionally
      eloquent are as of the spinal cord during the surgical management of metastatic
      tumors.

PMID- 15450889
TI  - Clinical trials and evidence-based medicine for metastatic spine disease.
AB  - Treatment of metastatic epidural spinal disease has undergone significant changes
      over the last 20 years. No longer is indiscriminate decompressive laminectomy
      offered as the only surgical treatment. It carries all the risks associated with
      an invasive procedure and offers the patient little benefit unless it is used to
      remove disease isolated to the posterior elements. The existing literature
      suggests that surgery that frees the spinal cord at the site of compression in
      addition to reconstructing and stabilizing the spinal column is more effective at
      preserving and regaining neural function, notably ambulatory function and
      sphincter function, than conventional radiotherapy. It is also highly effective
      in relieving pain. The preliminary results ofa recent RCT provide the first class
      I evidence to support a reversal in the current philosophy of primary treatment
      for many patients with meta-static disease. Conventional radiotherapy has a
      clearly defined role as adjuvant therapy and as primary therapy in those who are
      unable to tolerate or benefit significantly from surgery. The role of
      nonconventional radiation therapy, such as IMRT and SRS, remains to be
      elucidated.

PMID- 15450891
TI  - Metastatic spine disease.

PMID- 15450892
TI  - Anatomic considerations of the human nail.
AB  - This article provides a description of the growth and anatomic structure of the
      human nails.

PMID- 15450893
TI  - Imaging of tumors of the nail unit.
AB  - In case of suspicion of a deep mass beneath the nail plate, radiographs remain
      necessary to assess the distal phalanx and the distal interphalangeal joint.
      Ultrasonography may be helpful to depict a cystic or a vascular component of a
      tumor. Computed tomography is only indicated to accurately assess tiny
      abnormalities of the cortex of the distal phalanx. MR imaging offers a whole
      imaging of the soft parts of the nail unit and the underlying bone.

PMID- 15450894
TI  - Imaging of the nail unit and toes-a pictorial review. Illuminating newer
      techniques by looking "back to the future".
AB  - Despite a number of multimodality options now available when imaging the distal
      digits for potential pathology, the plain radiograph remains the everyday
      "workhorse" in podiatric medical practice. This section will illustrate how
      looking back to simple basics can provide new pathways to future practice.

PMID- 15450895
TI  - Origins of onychomycosis.
AB  - Onychomycosis, or tinea unguium, is generically thought of as a fungus infection
      of the nails characterized by thickening, splitting, roughening, and
      discoloration. This article discusses the origins of this condition as well as
      methods of classification and evaluation.

PMID- 15450896
TI  - Curing onychomycosis: understanding the multitude of variables.
AB  - This article provides a focused look at the need to treat onychomycosis from a
      podiatric perspective, new classifications of the disorder, definitive diagnostic
      methods, predictability of host responsiveness, and current strategies for
      treatment.

PMID- 15450897
TI  - Laboratory diagnosis of onychomycosis.
AB  - Onychomycosis (fungal nail infection) has come to public attention with the
      availability of effective oral therapy. The natural history and etiologic agents
      of this disease are discussed. The currently available methods of laboratory
      diagnosis are compared and contrasted.

PMID- 15450898
TI  - The systemic treatment of onychomycosis.
AB  - The systemic treatment of fungal infections has changed considerably over the
      past 10 to 20 years. Though griseofulvin was introduced in the late 1950s and was
      at the time the only Food and Drug Administration (FDA)-approved drug in the
      United States for the systemic treatment of onychomycosis, its cure rate seldom
      exceeds 40%. Newer drugs appear to be reducing treatment times, improving cure
      rates with a minimum of side effects, and achieving long-term remissions in
      recalcitrant infections. Itraconazole was FDA approved in 1995, and terbinafine
      was FDA approved in 1996. Both have been used safely for many years,
      demonstrating efficacy in short-term treatment with a low incidence of side
      effects. Fluconazole, though not yet FDA approved for onychomycosis, has also
      shown efficacy in many situations. Direct-to-the-public advertising has raised
      interest in patients to seek treatment. There are also some new investigational
      drugs for fungal infections that may augment or supplant current therapy.

PMID- 15450899
TI  - The oral antifungal patient.
AB  - With the launch of the modern generation of oral antifungals almost a decade ago,
      an infection that was once thought of as intractable can now be cured. These
      drugs all offer the advantages of high efficacy rates, short-course therapy, and
      relative safety. However, they are far from perfect and not indicated in every
      situation. This article discusses issues such as patient selection, management,
      monitoring, and long-term follow-up.

PMID- 15450900
TI  - Management of onychomycosis with topicals.
AB  - Of all superficial fungal infections, onychomycosis is the most difficult to
      manage. Practitioners of all disciplines realize its chronic nature, difficulty
      in eradication, and propensity to recur. Topical treatment of onychomycosis, as
      opposed to oral therapies, offers a distinct advantage by allowing the patient to
      apply medication directly to the affected area, thus decreasing the potential for
      serious adverse events, such as drug toxicity and drug interactions. In the past,
      a multitude of topical antifungal agents were used in the treatment of
      onychomycosis; however, an acceptable level of scientific evidence regarding
      their effectiveness was lacking and this was evident by poor success rates. The
      development of a comparatively effective topical agent, the only one so far to
      gain FDA approval, has renewed interest in this form of therapy. Improved
      versions are being developed that may overcome the shortcomings of the first
      approved topical agent.

PMID- 15450901
TI  - Onychocryptosis.
AB  - Onychocryptosis is prevalent globally and most often the result of self-attempts
      at curing the condition in its earliest stages. Its clinical presentation is
      often confused with a number of osseous and soft tissue abnormalities, some of
      which have great import to a patient's overall welfare. Treatment consists of
      local and systemic care, including nail avulsion. Recurrences are reduced when
      some form of matricectomy is used. Matricectomy techniques vary and must be
      selected on the basis of caregiver and patient preference. Although the chemical
      matricectomy is popular, care must be exercised in selecting patients for its
      use.

PMID- 15450902
TI  - Nail manifestations of systemic diseases.
AB  - This article is a guide to nail evaluation, focusing on the more prominent nail
      dystrophies and related systemic diseases that the podiatrist is most likely to
      encounter. This article classifies systemic illnesses by their relationship to
      specific nail abnormalities.

PMID- 15450903
TI  - Pediatric nail disorders.
AB  - This article lists common pediatric nail disorders seen in infancy and
      adolescence. The diagnosis of pediatric nail disorders can be a sign of systemic
      disorders and diseases. The surgical treatment of young children and the
      treatment of pediatric patients are presented for those who do not frequently
      treat pediatric patients. The analysis of pediatric onychomycosis is presented,
      and the incidence and prevalence in the population is discussed.

PMID- 15450904
TI  - Periungual verrucae diagnosis and treatment.
AB  - To diagnose periungual verrucae, the practitioner must be able to rely on
      clinical judgment and choose the best treatment for the patient. This article
      provides multiple treatment options with advantages and disadvantage to aid the
      decision-making process.

PMID- 15450905
TI  - Nail dystrophies.
AB  - Various individual nail dystrophies that are not easily categorized within other
      articles are reviewed. Onychoatrophia, anonychia, onychorrhexsis, leukonychia,
      Beau's lines, onycholysis, onychomadesis, onychoschizia, haplonychia,
      longitudinal melanonychia, and ventral pterygium are included and clinically
      pictured. Their clinical description, etiology, associated conditions,
      differential diagnoses, and treatment are discussed and tabulated. In addition,
      several clinical severity-scoring methods are presented.

PMID- 15450906
TI  - The use of the distal Syme's procedure for treating onychopathy.
AB  - There are many procedures available to the podiatric surgeon to deal with a
      painful, deformed nail. The Syme's procedure should not be overlooked, though
      more conservative options should be attempted before this procedure. With the
      proper surgical candidate (ie, intact neurovascular status), this is a
      successful, safe procedure easy to perform under local anesthesia.

PMID- 15450909
TI  - Microtubule-associated protein MAP2 expression in olfactory bulb in
      schizophrenia.
AB  - Previous studies have described alterations in presynaptic and postsynaptic
      elements in various parts of the CNS in schizophrenia, which may, at least in
      part, be due to abnormalities in neurodevelopmental processes. The olfactory bulb
      (OB) is a unique CNS area for examining synaptic development and plasticity in
      schizophrenia because it undergoes continuous reinnervation throughout life.
      Moreover, olfactory deficits and reduced OB volume have been observed in
      schizophrenia. We investigated the expression in the OB of the microtubule
      associated protein MAP2, which has been shown to be abnormally expressed in the
      hippocampal region in schizophrenia. In both developing and mature neurons, MAP2
      is an important structural component of dendrites and participates in the
      modification of synaptic organization. We used immunocytochemistry with
      phosphoepitope-specific and phosphorylation-state-independent antibodies to
      examine MAP2 expression in the glomerular layer of the OB in elderly subjects
      with chronic schizophrenia and controls. Phosphorylation-independent MAP2
      expression was significantly reduced in schizophrenia, while phosphorylated MAP2
      expression did not differ between groups. These results are consistent with
      faulty OB innervation in schizophrenia.

PMID- 15450910
TI  - Clozapine reduces alcohol drinking in Syrian golden hamsters.
AB  - Alcohol abuse contributes substantially to the overall morbidity of
      schizophrenia. While typical antipsychotic medications do not limit alcohol use
      in patients with schizophrenia, emerging data suggest that the atypical
      antipsychotic clozapine does. To further elucidate the effects of these
      antipsychotics on alcohol use, we initiated a study in alcohol-preferring
      rodents. Syrian golden hamsters were given free-choice, unlimited access to
      alcohol. Nine days of treatment (s.c. injection) with clozapine (2-4 mg/kg/day),
      but not haloperidol (0.2-0.4 mg/kg/day), reduced alcohol drinking. Clozapine
      reduced alcohol drinking by 88% (from 11.3+/-1.7 to 1.4+/-0.2 g/kg/day) while
      increasing both water and food intake. Alcohol drinking gradually (during 24
      days) returned toward baseline in the clozapine-treated animals when vehicle was
      substituted for clozapine. Further increasing the doses of haloperidol (0.6-1.0
      mg/kg/day) had no effect on alcohol drinking; moreover, very low doses of
      haloperidol (0.025-0.1 mg/kg/day) tested in separate groups of hamsters also had
      no effect on alcohol drinking. This study demonstrates that clozapine, but not
      haloperidol, can effectively and reversibly decrease alcohol consumption in
      alcohol-preferring hamsters. The results are compatible with the observations
      that clozapine, but not haloperidol, limits alcohol use in patients with
      schizophrenia. These data further suggest that clozapine may serve as a prototype
      for developing novel treatments for alcohol abuse.

PMID- 15450911
TI  - Association studies of MAO-A, COMT, and 5-HTT genes polymorphisms in patients
      with anxiety disorders of the phobic spectrum.
AB  - Recent studies provide evidence that anxiety disorders may be linked to
      malfunction of serotonin neurotransmission or impaired activity of enzymes
      metabolising the catecholamines. Functional polymorphisms in the MAO-A uVNTR
      promoter gene, the COMT gene (Val158Met) exon 4, and the 5-HTT promoter gene (44
      bp ins/del) were investigated in 101 patients with phobic disorders of the
      anxiety spectrum and 202 controls matched to the patients for sex, age and
      ethnicity. There were no significant differences between controls and patients in
      the allele and genotype frequencies of the 5-HTT and COMT gene polymorphisms. The
      frequency of >3 repeat alleles of the MAO-A gene polymorphism was significantly
      higher in female patients suffering from anxiety disorders, specifically panic
      attacks and generalized anxiety disorder. There was also a trend for the more
      frequent presence of >3 repeat alleles in female patients with agoraphobia and
      specific phobia, in contrast to female patients with social phobia, who did not
      differ from controls. The results support a possible role of the MAO-A gene in
      anxiety disorders.

PMID- 15450912
TI  - Memory profiles in parents of patients with schizophrenia.
AB  - Recent research shows that categorizing patients with schizophrenia based on
      frontal-striatal and frontal-temporal memory profiles may yield neurobiologically
      meaningful disease subtypes. We hypothesize that parents of patients exhibit
      similar memory profiles. Both parents of 36 patients with schizophrenia (N = 72)
      and 26 healthy married control couples (N = 52) participated in this study. All
      subjects were physically healthy and had no history of neurological illness or
      alcohol/drug abuse. The presence of a psychiatric and/or personality disorder was
      assessed with the Comprehensive Assessment of Symptoms and History (CASH)
      interview, the Schedule for Affective Disorders and Schizophrenia-lifetime (SADS
      L) interview and the Structured Interview for DSM-IV Personality Disorders (SIDP
      IV), respectively. Cluster analysis of selected measures from the Dutch version
      of the California Verbal Learning Test (CVLT) delineated parents into two
      subgroups with distinct memory deficits and a third subgroup without impairments.
      Specific frontal-striatal and frontal-temporal subgroups, however, were not
      found. In addition, our results indicated that mothers seem to be more protected
      against the negative effects of genetic liability to schizophrenia than fathers.
      Furthermore, relatives with a higher level of intelligence may have more
      cognitive reserve to compensate for the negative impact of implied brain
      dysfunction on verbal memory than relatives with a low level of intelligence.
      Although the parents of patients with schizophrenia could be delineated into
      subgroups with primary memory deficits, frontal-striatal and frontal-temporal
      subgroups could not be unambiguously identified. The association that emerged
      between level of intelligence, gender and severity of memory impairment deserves
      further exploration.

PMID- 15450913
TI  - Perception of dynamic action in patients with schizophrenia.
AB  - Neuropsychological studies have revealed that schizophrenic (SZ) patients have
      severe impairments in the cognitive integration of static and moving perceptual
      stimuli. Research on knowledge structures has shown that sequences of continuous
      actions are represented in memory as clusters of goal-directed events in a
      hierarchical manner. In the present study, we investigated the ability to segment
      familiar sequences of dynamic goal-directed actions into small and large
      meaningful units in a group of patients with schizophrenia (N = 16) and a group
      of healthy control subjects (N = 17). While viewing two videotaped movies,
      participants were requested to detect the transitions between component events at
      both low and high levels of the action categorical structure. Both groups
      detected significantly more events under the small-oriented condition as compared
      to the large-oriented condition. Differently from normal controls, patients
      recalled the event scenes in a detailed and fragmentary manner and showed
      considerable difficulties in detecting large action units. Moreover, low
      performance on action boundary detection significantly correlated with higher
      levels of disorganisation symptoms in patients with schizophrenia. A defective
      conceptual organisation of perceptive action knowledge would help to explain the
      severe everyday difficulties of these patients both in monitoring their own
      actions and in understanding others' intentions.

PMID- 15450914
TI  - Suppression of P50 evoked potential component, schizotypal beliefs and smoking.
AB  - Suppression of the P50 component of the evoked potential is an
      electrophysiological index of sensory gating that is blunted in schizophrenia
      spectrum disorders. Although P50 suppression is thought to be related to
      symptomatology, this is yet to be shown. The failure to demonstrate this relation
      has led some to argue that P50 suppression and symptomatology are not related.
      However, a possible confound has recently been corroborated [i.e., chronic
      smoking is related to superior P50 suppression [Crawford et al., Neuroscience
      Letters 317 (2002) 151]], and a relation has been found in questionnaire-defined
      individuals with indications of schizotypy [i.e., psychometric schizotypy is
      related to poor P50 suppression [Croft et al., Biological Psychiatry 50 (2001)
      441]]. The present study attempted to replicate and extend both studies by
      examining P50 suppression, smoking histories, psychometric schizotypy and NEO
      Five-Factor Inventory (NEO-V) scores in 37 healthy participants. Replicating
      Crawford et al., P50 suppression was better in the heavier smokers. Providing a
      partial replication of Croft et al., P50 suppression was inversely related to
      schizotypy scores in participants who smoked little or not at all; however, P50
      suppression was positively related to schizotypy in heavier smokers. Covarying
      for age and NEO-V scale scores had little effect on these relations. The findings
      provide evidence of important confounds that would limit our ability to detect
      P50 suppression/symptom relations in schizophrenia.

PMID- 15450915
TI  - Lower limb motor restlessness in Asperger's disorder, measured using actometry.
AB  - The movement disturbances and brain imaging findings in Asperger's disorder (AD)
      suggest a dopaminergic deficit in movement regulation. Movement disorders of
      different etiologies have been quantified and specified with actometry. We
      compared 10 AD patients with 10 healthy controls, measuring their rest-activities
      by actometry. The lower limb motor activity was significantly higher in the AD
      group. They also displayed a rhythmic, periodic movement pattern similar to
      akathisia. These findings suggest a hypothesis of idiopathic akathisia and a
      special sensitivity to adverse effects of neuroleptic drugs.

PMID- 15450916
TI  - Sensitivity to change of scales assessing symptoms of bulimia nervosa.
AB  - Measures employed in a therapy study with a pre-post design must be sensitive to
      the detection of treatment-related changes. In the present study, the treatment
      sensitivity of 12 internationally established scales that assess bulimia-relevant
      aspects of eating and body concern is analyzed. The scales can be sorted along
      three dimensions (Disturbed Eating, Restrictive Eating Behaviors and Body
      Dissatisfaction). Measures of the same dimension were compared in a sample of 45
      women with the diagnosis of bulimia nervosa. Patients completed the scales before
      and 6 weeks after the end of cognitive-behavioral therapy. Significant
      differences between scales with respect to treatment sensitivity occurred in all
      three dimensions. Post hoc analysis revealed that scales are particularly
      sensitive to change if they include disorder-relevant aspects beyond the main
      dimension of a scale. Implications of the findings for meta-analytical treatment
      research, for designing effectiveness studies, and for future research on the
      treatment sensitivity of outcome measures are discussed.

PMID- 15450917
TI  - Preliminary validity and reliability testing of a structured clinical interview
      for pathological gambling.
AB  - The psychometric properties of a clinician-administered, DSM-IV-based, structured
      clinical interview for pathological gambling (SCI-PG) were examined. Seventy-two
      consecutive subjects requesting treatment for gambling problems were administered
      the SCI-PG. Reliability and validity were determined. Classification accuracy was
      examined using longitudinal course of illness. The SCI-PG demonstrated excellent
      inter-rater and test-retest reliability. Concurrent validity was observed with
      the South Oaks Gambling Screen (SOGS). Discriminant validity was observed with
      measures of anxiety and depression. The SCI-PG demonstrated both high sensitivity
      and specificity based on longitudinal assessment. The SCI-PG demonstrated
      excellent reliability and validity in diagnosing PG in subjects presenting with
      gambling problems. These findings require replication in other groups to examine
      their generalizability.

PMID- 15450918
TI  - Associations between psychiatric patients' self-image, staff feelings towards
      them, and treatment outcome.
AB  - Interpersonal theory, as well as relational models of psychoanalytic and
      cognitive therapy, posits the importance for positive treatment outcome of the
      therapist's becoming emotionally involved in the patient's interpersonal
      patterns. Using the same data as in this study, we have previously found
      associations between psychiatric patients' self-image and the staff's feelings
      towards them, and differential associations between staff feelings and outcome
      for different diagnostic groups. The purpose of the present study was to analyze
      potential connections between patients' self-image, staff feelings, and outcome.
      Twice a year, staff at small psychiatric units reported their feelings towards 63
      psychotic and 21 borderline patients who had rated their self-image at the
      beginning of the treatment using the Structural Analysis of Social Behavior
      (SASB) introject and parent images. Feelings reported on the two first occasions
      at the beginning of the treatment were used. Outcome was assessed after 5 years.
      Correlation analyses found different associations between patient self-image and
      staff feelings for patients with favorable and less favorable outcome. The
      results indicated for psychotic patients associations between positive outcome
      and less distant staff feelings connected with the patient's freedom-giving
      introject, less unfree staff feelings connected with a negative image of mother
      and less positive feelings connected with a positive image of father. For the
      borderline patients, positive outcome was associated with the fact that a
      negative image of mother did not evoke helpful staff feelings, a positive image
      of the patient himself or herself did not evoke helpful staff feelings and a
      controlling image of father-evoked distant feelings.

PMID- 15450919
TI  - Psychomotor, neuroendocrine and behavioural effects after oral administration of
      levodopa in normal volunteers.
AB  - The oral administration of a single dose of levodopa (L-dopa) in 10 healthy human
      male subjects induced cognitive, not motor, changes during figure-copying tasks
      that were unrelated to the neuroendocrine and behavioural effects of levodopa.
      Results point to a decrease in alertness induced by levodopa.

PMID- 15450920
TI  - Ricin: the endoplasmic reticulum connection.
AB  - Ricin is a potent, plant-derived, ribosome inactivating protein. To target
      ribosomes in the mammalian cytosol, ricin must firstly negotiate the endomembrane
      system of the cell to reach the endoplasmic reticulum. Here, the toxin is reduced
      and the catalytic A chain is recognised by ER components that facilitate its
      membrane translocation to the cytosol. To be toxic, ricin A chain must then avoid
      degradation, a conundrum made more tricky in that ubiquitination and proteasomal
      degradation are normally tightly coupled to the translocation process. This mini
      review summarises current understanding of these events.

PMID- 15450921
TI  - Signalling pathways regulating human neutrophil migration induced by secretory
      phospholipases A2.
AB  - This study was designed to elucidate the signalling pathways by which secretory
      phospholipases A2 (sPLA2s) induce in vitro neutrophil migration. The cell
      migration assays were performed with Naja mocambique venom PLA2 (sPLA2 with high
      catalytic activity), bothropstoxin-I (sPLA2 devoid of catalytic activity) and
      platelet-activating factor (PAF), using a 48-well microchemotaxis chamber. Both
      the non-selective protein kinase inhibitor staurosporine (30-300 nM) and the
      selective protein kinase C (PKC) inhibitor 1-(5-isoquinolinesulfonyl)-2
      methylpyperazine (H7; 50-200 microM) as well as the Gi inactivator pertussis
      toxin (30-300 nM) caused a concentration-dependent inhibition of the neutrophil
      migration induced by either N. mocambique venom PLA2 (100 microg/ml) or
      bothropstoxin-I (100 microg/ml). Pertussis toxin nearly abolished PAF-induced
      migration, while staurosporine and H7 partly (but significantly) inhibited the
      chemotactic responses to PAF. The dual inhibitor of cytosolic PLA2 and Ca2+ 
      independent PLA2 (iPLA2), arachidonil-trifluoromethyl-ketone (ATK; 0.2-20
      microM), or the specific iPLA2 inhibitor bromoenol lactone (1-30 microM) caused a
      concentration-dependent inhibition of the migration induced by either sPLA2s. At
      the maximal concentration used for each compound, the migration was almost
      suppressed. In contrast, both of these compounds caused only slight inhibitions
      of PAF-induced migration. No rise in intracellular Ca2+ was observed in
      neutrophil-stimulated sPLA2, as determined in cells preloaded with fura 2-AM. In
      the experimental condition used, pertussis toxin, staurosporine, H7, ATK or
      bromoenol lactone did not induce cytotoxic effects, according to MTT assay. Our
      results suggest that activation of an endogenous PLA2 through activation of GTP
      binding protein and PKC is the main mechanism by which exogenous sPLA2s cause
      neutrophil migration.

PMID- 15450922
TI  - The effect of temperature on growth and production of paralytic shellfish
      poisoning toxins by the cyanobacterium Cylindrospermopsis raciborskii C10.
AB  - Cylindrospermopsis raciborskii is a cyanobacterium which produces either
      cylindrospermopsine or paralytic shellfish poisoning (PSP) toxins. We studied the
      effect of temperature on growth and production of PSP toxins by C. raciborskii
      C10, isolated from a freshwater reservoir in Brazil. We analyzed the
      extracellular and intracellular content of PSP toxins at two different
      temperatures: 19 and 25 degrees C. C. raciborskii C10 produces STX, GTX2, and
      GTX3 at both temperatures. dcSTX was also detected at 25 degrees C in the
      intracellular extracts obtained at the end of the stationary phase. The growth
      achieved at 25 degrees C and estimated by optical density at 700 nm was three
      times greater than at 19 degrees C. However, no significant differences were
      observed in the content of PSP toxins in either the cells or the extracellular
      media. The kinetics of accumulation of PSP toxins within the cells rather than in
      the media suggests an active PSP toxins-export process that is not related to
      cell lysis. The extracellular accumulation of PSP toxins at 19 degrees C
      suggested a biotransformation of STX to the epimers GTX2 and GTX3. The stability
      of the PSP toxins produced by C. raciborskii C10 was high enough for them to
      remain active in the media after 30 days (at 25 degrees C) or after 50 days (at
      19 degrees C).

PMID- 15450923
TI  - Chemical modification of arginine residues of Notechis scutatus scutatus notexin.
AB  - Notexin, a presynaptic phospholipase A2 (PLA2) neurotoxin isolated from Notechis
      scutatus scutatus venom, was inactivated by arginine-specific reagents,
      phenylglyoxal and 1,2-cyclohexanedione. Kinetic analyses of the modification
      reaction revealed that the inactivation of notexin followed pseudo-first order
      kinetics and the loss of PLA2 activity was correlated with the incorporation of
      one molecule of modification reagent per toxin molecule. However, the results of
      amino acid analysis and sequence determination revealed that two arginine
      residues at positions 43 and 79 of notexin were modified simultaneously.
      Modification of the arginine residues was accompanied with a decrease in the
      ability to inhibit the indirectly evoked contraction of chick biventer cervicis
      muscle and bind with synaptic membranes. The secondary structure of the toxin
      molecule did not significantly change after modification with phenylglyoxal as
      revealed by the CD spectra. The modified derivative retained its affinity for
      Ca2+, indicating that the modified arginine residues did not participate in Ca2+ 
      binding. Together with the notion that Arg-43 and Arg-79 of notexin are located
      in the proximity of its catalytic site and toxic site, respectively, our results
      suggest that modification of Arg-43 and Arg-79 should differently contribute to
      the observed decrease in the PLA2 activity and neurotoxic effect of notexin.

PMID- 15450924
TI  - Plancitoxins, lethal factors from the crown-of-thorns starfish Acanthaster
      planci, are deoxyribonucleases II.
AB  - Two lethal factors (named plancitoxins I and II for major and minor toxins,
      respectively) with the same LD50 (i.v. injection into mice) of 140 microg/kg were
      purified from spines of the crown-of-thorns starfish Acanthaster planci.
      Injection of a sublethal dose of plancitoxin I or II into mice remarkably
      elevated serum levels of glutamic oxaloacetic transaminase and glutamic pyruvic
      transaminase, demonstrating that both toxins are potently hepatotoxic. Analysis
      by SDS-PAGE revealed that both plancitoxins are composed of two subunits (alpha
      subunit of 10 kDa and beta-subunit of 27 kDa) bridged by a disulfide bond. Based
      on the determined N-terminal amino acid sequences of alpha- and beta-subunits,
      the full-length cDNA (1820 bp) encoding plancitoxin I was cloned by RT-PCR, 3'
      RACE and 5'-RACE. alpha-Subunit (92 amino acid residues) and beta-subunit (240
      residues) are coded in this order by the same cDNA. Interestingly, the deduced
      amino acid sequence of plancitoxin I showed 40-42% homologies with mammalian
      deoxyribonucleases II (DNases II). In addition, plancitoxin I exhibited DNA
      degrading activity with an optimum pH of 7.2. Plancitoxin I is the first example
      of toxic DNases II whose structures have been elucidated.

PMID- 15450925
TI  - Genetic and enzymatic characterization of sphingomyelinase D isoforms from the
      North American fiddleback spiders Loxosceles boneti and Loxosceles reclusa.
AB  - In this study we report the isolation and characterization of several
      sphingomyelinase D isoforms from the venoms of the North American spiders
      Loxosceles boneti and Loxosceles reclusa, from Mexico and the United States,
      respectively. We have measured their enzymatic activity, their capacity to induce
      necrotic lesions in rabbits, cloned the cDNAs coding for the mature forms of two
      of the isoforms from L. boneti and two of L. reclusa based on N-terminal sequence
      information of the purified proteins, and performed a comprehensive comparison of
      the sequence data generated by us with that reported for other sphingomyelinase
      genes to date.

PMID- 15450926
TI  - Immunoenzymatic visualization of tetrodotoxin (TTX) in Cephalothrix species
      (Nemertea: Anopla: Palaeonemertea: Cephalotrichidae) and Planocera reticulata
      (Platyhelminthes: Turbellaria: Polycladida: Planoceridae).
AB  - Tetrodotoxin (TTX) was localized as brown color in different tissues of an
      undescribed species of the nemertean genus Cephalothrix (phylum Nemertea) and a
      turbellarian Planocera reticulata (phylum Platyhelminthes) on light microscopy by
      means of a monoclonal anti-TTX antibody. In the Cephalothrix sp., TTX was
      recognized in the vesicles apically arranged in the bacillary cells in the
      epidermis, basal lamina, the granular cells in the proboscis epithelium,
      rhynchocoel epithelium, and the vesicles in the basal portion of the intestinal
      wall near the blood vessels and rhynchocoel. The excretory system and the ovum
      also showed positive reaction of TTX antigen-antibody. On the other hand, the
      hermaphrodite flatworm P. reticulata exhibited TTX antigen-antibody complex only
      in their ovum. To our knowledge, this is the first experimental effort on micro
      distribution of TTX in invertebrates.

PMID- 15450927
TI  - Permeability of human jejunal segments to gonyautoxins measured by the Ussing
      chamber technique.
AB  - The aim of this work was to study the mechanisms involved in intestinal
      permeability of gonyautoxins. For this purpose, the influence on transmucosal
      resistance of gonyautoxins and their permeability was investigated in excised
      human jejunal segments. To evaluate these events, the isolated mucosa was mounted
      in Ussing chambers for electrophysiological characterization. The organic
      gonyautoxin cations were applied to the mucosal side and samples collected on the
      serosal side. The permeability of gonyautoxins measured at 37 degrees C was 4.3
      fold greater than at 4 degrees C, indicative of high cation selective
      transcellular permeability. In order to characterize the permeability of
      gonyautoxins, the effects of choline, ouabain, phlorizin and fluorescein were
      studied. The inhibition by these compounds was expressed as percent inhibition of
      the maximal flux of gonyautoxins at 120 min. Replacement of sodium ion by
      choline, showed the highest inhibition (85.5% from control). Ouabain, fluorescein
      and phlorizin inhibit the gonyautoxins flux by 53.9, 41.0 and 9.64%,
      respectively. The inhibition of gonyautoxins' permeability produced by ouabain
      and phlorizin go in parallel with an increase in the transmucosal electrical
      resistance (TER). This study shows that permeability of gonyautoxin cations
      occurred predominantly by the transcellular pathway (76%) when toxins were
      applied in the mucosal-serosal direction. The paracellular pathway of
      gonyautoxins was 24% of total permeability when compared with [3H] mannitol
      permeability. These findings suggests that permeability of gonyautoxins depends
      on temperature and processes involving sodium ion. Replacing sodium ions by
      choline ions showed a marked effect on TER.

PMID- 15450928
TI  - Comparative analysis of the catalytic domain of hemorrhagic and non-hemorrhagic
      snake venom metallopeptidases using bioinformatic tools.
AB  - Snake venom metalloproteases (SVMPs) are a set of interesting enzymes that are
      one of the major components of venom affecting hemostasis. A great challenge
      since their discovery has been to find molecular features responsible for their
      hemorrhagic potency and many attempts have been made without any consistent
      result. Here we describe a series of comparisons between the catalytic domains of
      hemorrhagic and non-hemorrhagic SVMPs made with the help of bioinformatics. These
      involved sequence and structure-based multiple alignments, phylogenetic
      reconstruction, predicted physical and chemical properties, motif scanning and
      structural analyses. Although hemorrhagic activity seems to be complex, involving
      multiple factors, we found some molecular characteristics that may influence the
      toxic effects. Among these findings, it was possible to use a molecular surface
      feature to subdivide the P-I class in hemorrhagic and non-hemorrhagic SVMPs. It
      was also possible to suggest a role for the conserved Asp148 and Ser176 residues
      in the stabilization of the active site.

PMID- 15450929
TI  - Novel conopeptides of the I-superfamily occur in several clades of cone snails.
AB  - The I-superfamily of conotoxins represents a new class of peptides in the venom
      of some Conus species. These toxins are characterized by four disulfide bridges
      and inhibit or modify ion channels of nerve cells. When testing venoms from 11
      Conus species for a functional characterization, blocking activity on potassium
      channels (like Kv1.1 and Kv1.3 channels, but not Kv1.2 channels) was detected in
      the venom of Conus capitaneus, Conus miles, Conus vexillum and Conus virgo.
      Analysis at the cDNA level of these venoms using primers designed according to
      the amino acid sequence of a potassium channel blocking toxin (ViTx) from C.
      virgo confirmed the presence of structurally homologous peptides in these venoms.
      Moreover, peptides belonging to the I-superfamily, but with divergent amino acid
      sequences, were found in Conus striatus and Conus imperialis. In all cases, the
      sequences of the precursors' prepro-regions exhibited high conservation, whereas
      the sequences of the mature peptides ranged from almost identical to highly
      divergent between species. We then performed phylogenetic analyses of new and
      published mitochondrial 16S rDNA sequences representing 104 haplotypes from these
      and numerous other Conus species, using Bayesian, maximum-likelihood, maximum
      parsimony and neighbor-joining methods of inference. Cone snails known to possess
      I-superfamily toxins were assigned to five different major clades in all of the
      resulting gene trees. Moreover, I-superfamily conopeptides were detected both in
      vermivorous and piscivorous species of Conus, thus demonstrating the widespread
      presence of such toxins in this speciose genus beyond evolutionary and ecological
      groups.

PMID- 15450930
TI  - Use of high performance liquid chromatography to measure tetrodotoxin in serum
      and urine of poisoned patients.
AB  - Tetrodotoxin (TTX) poisoning is an infrequent but important problem in South
      eastern Asia. Despite it being a considerable public health issue in some
      countries and its potential lethality there continues to be no readily available
      method for measuring TTX in urine or serum. Previously published methods have
      used immunoaffinity chromatography, or the conversion of TTX to its C9-base
      derivative for measurement by mass spectrometry. A simple and reproducible method
      was developed using solid phase extraction cartridges to clean up serum and urine
      samples from TTX-poisoned patients, and the subsequent analysis of the samples by
      high performance liquid chromatography with post-column derivatisation and
      fluorescence detection. Minimum quantifiable concentrations of TTX were 5 and 20
      ng/ml for serum and urine, respectively. Precision and accuracy of the assay were
      13 and 15%, respectively. The standard curves were linear in the range of 20-300
      ng/ml for urine and 5-20 ng/ml for serum. TTX was quantified in six samples of
      urine and six samples of serum from seven patients who ingested common toadfish
      and had clinical effects consistent with TTX poisoning. TTX was detected in all
      urine samples but in only one serum sample. Using this method confirmation of TTX
      poisoning will be far simpler and readily available. A 24 h urine collection in
      the period immediately following poisoning is likely to be the most sensitive
      test for TTX poisoning. With appropriately collected and timed serum and urine
      specimens it will be possible to properly define the pharmacokinetics of TTX in
      humans.

PMID- 15450931
TI  - Microcystin-LR promote intestinal secretion of water and electrolytes in rats.
AB  - We showed previously that exposure to microcystin-LR causes renal toxic effects
      in isolated perfused rat kidney, and that inflammatory mediators from
      supernatants of macrophages stimulated by microcystin-LR are involved in this
      process. The aim of this research was to examine water and electrolytes secretion
      in vivo, induced by microcystin-LR and supernatant of macrophages stimulated for
      this toxin (SUP.MphiS + MCLR), using perfused rat ileal segment and ligated
      intestinal loop models. We found microcystin-LR at 1 microg/ml (0.09 +/- 0.003*
      vs. control 0.07 +/- 0.001 g of secretion/2 cm of loop; P < 0.05*) and the
      SUP.MphiS + MCLR after 18 h postinoculation (0.10 +/- 0.003 vs. control 0.03 +/-
      0.002 g/cm) caused intestinal secretion. In addition, microcystin-LR caused
      significant sodium secretion (-2.18 +/- 0.72* vs. control 2.18 +/- 0.50 microEq
      g(-1) min(-1)), potassium (-0.26 +/- 0.04* vs. control 0.32 +/- 0.03 microEq g(
      1) min(-1)), chloride (MCLR = -3.29 +/- 1.93* vs. control 0.88 +/- 1.25 microEq
      g(-1) min(-1)) and water (-0.012 +/- 0.004* vs. control 0.002 +/- 0.002 ml g(-1)
      min(-1)). We also demonstrated SUP.MphiS + MCLR to induce intestinal secretion of
      electrolytes (sodium, potassium, chloride) and water. These findings suggested
      that microcystin-LR and lamina propria macrophages-derived mediators are able to
      induce intestinal secretion in vivo, probably via inhibition of protein
      phosphatase.

PMID- 15450932
TI  - Detection and analysis of the cyanobacterial peptide hepatotoxins microcystin and
      nodularin using SELDI-TOF mass spectrometry.
AB  - Surface-enhanced laser desorption ionization mass spectrometry (SELDI-TOFMS) was
      used to develop a new and useful method for determination and identification of
      the cyanobacterial (blue-green algae) toxins: microcystin and nodularin. The
      technique, combining chromatography and MS, enables microcystin/nodularin
      capture, purification, analysis, and processing from complex biological mixtures
      directly onto a hydrophobic chip. Factors affecting ion intensities, including
      matrix concentration and laser intensity, were investigated to optimize
      sensitivity of the method. Microcystins and nodularin were analyzed for
      femtomolar sensitivity (about 2.5 pg microcystin-LR in 2 microl water). Samples
      of blood sera and liver tissue were spiked with microcystin-LR and analyzed. The
      detection limit was 1 ng in 2 microl blood sera solution. Reactions of
      microcystins by compounds containing mercaptan groups, such as dithiothreitol,
      aminoethanethiol and protein phosphatase 1, were examined on the chip by mass
      spectrometry. Formation of the microcystin-dithiothreitol conjugate was used to
      confirm the target compounds. The MS/MS data obtained showed the presence of the
      microcystin conjugate. The reaction position of the toxin with target compound
      was confirmed by a series of MS/MS fragment ions. The protein profile of
      microcystins reacting with protein phosphatase 1 was also obtained from the SELDI
      TOF mass spectra.

PMID- 15450933
TI  - Identification and cloning of snake venom vascular endothelial growth factor
      (svVEGF) from Bothrops erythromelas pitviper.
AB  - Vascular endothelial growth factors (VEGFs) are among the most important
      angiogenic proteins found on vertebrates. In the last years, some reports of the
      occurrence of such proteins in snake venoms are rising the importance of this
      family of proteins as toxins, since they appear to be involved in many features
      of Viperidae envenoming, such as hypotension and venom spread through increase in
      vascular permeability. Here we describe the occurrence of snake venom VEGF in
      Bothrops erythromelas, a clinical important snake from Northeast of Brazil,
      through immunodetection and cloning of its cDNA and briefly provide an overview
      comparison of all recent described svVEGF sequences.

PMID- 15450934
TI  - On-demand activation of the endocannabinoid system in the control of neuronal
      excitability and epileptiform seizures.
AB  - Neurons intensively exchange information among each other using both inhibitory
      and excitatory neurotransmitters. However, if the balance of excitation and
      inhibition is perturbed, the intensity of excitatory transmission may exceed a
      certain threshold and epileptic seizures can occur. As the occurrence of epilepsy
      in the human population is about 1%, the search for therapeutic targets to
      alleviate seizures is warranted. Extracts of Cannabis sativa have a long history
      in the treatment of various neurological diseases, including epilepsy. However,
      cannabinoids have been reported to exert both pro- and anti-convulsive
      activities. The recent progress in understanding the endogenous cannabinoid
      system has allowed new insights into these opposing effects of cannabinoids. When
      excessive neuronal activity occurs, endocannabinoids are generated on demand and
      activate cannabinoid type 1 (CB1) receptors. Using mice lacking CB1 receptors in
      principal forebrain neurons in a model of epileptiform seizures, it was shown
      that CB1 receptors expressed on excitatory glutamatergic neurons mediate the anti
      convulsive activity of endocannabinoids. Systemic activation of CB1 receptors by
      exogenous cannabinoids, however, are anti- or pro-convulsive, depending on the
      seizure model used. The pro-convulsive activity of exogenous cannabinoids might
      be explained by the notion that CB1 receptors expressed on inhibitory GABAergic
      neurons are also activated, leading to a decreased release of GABA, and to a
      concomitant increase in seizure susceptibility. The concept that the endogenous
      cannabinoid system is activated on demand suggests that a promising strategy to
      alleviate seizure frequency is the enhancement of endocannabinoid levels by
      inhibiting the cellular uptake and the degradation of these endogenous compounds.

PMID- 15450935
TI  - Influence of p53 and caspase 3 activity on cell death and senescence in response
      to methotrexate in the breast tumor cell.
AB  - The influence of p53 function and caspase 3 activity on the capacity of the
      antifolate, methotrexate, to promote senescence arrest and apoptotic cell death
      was investigated in breast tumor cells. In p53 wild-type, but caspase 3 deficient
      MCF-7 breast tumor cells, death of approximately 40% of the cell population was
      observed immediately after acute exposure to 10 microM methotrexate (the IC80
      value for a 2 h drug exposure). There was no evidence of either DNA
      fragmentation, a sub G0 population or morphological alterations indicative of
      apoptosis; however, PARP cleavage was detected. Cell death was succeeded by
      growth arrest for at least 72 h--where arrest was characterized by expression of
      the senescence marker, beta-galactosidase. The response to methotrexate in MCF
      7/E6 cells with attenuated p53 function was also primarily growth arrest--but
      lacking characteristics of senescence. In contrast, MCF-7 cells which expressed
      caspase 3 demonstrated a gradual and continuous loss of cell viability and
      unequivocal morphological evidence of apoptosis. DNA fragmentation indicative of
      apoptosis was also detected after exposure to methotrexate in p53 mutant MDA
      MB231 breast tumor cells which also express caspase 3. Methotrexate-induced both
      p53 and p21waf1/cip1 in MCF-7 cells within 6 h; however, no significant DNA
      strand breakage was evident before 18 h, suggesting that the induction of p53
      reflects a response to cellular stress other than DNA damage, such as nucleotide
      depletion. Overall, these studies suggest that the nature of the cellular
      response to methotrexate depends, in large part, on p53 and caspase function. p53
      appears to be required for methotrexate-induced senescence, but not apoptosis,
      caspase 3 is required for DNA fragmentation and the morphological changes
      associated with apoptosis, while neither p53 nor caspase 3 are required for
      methotrexate-induced growth arrest. Furthermore, the senescence phenotype may
      occur in the absence of direct DNA damage.

PMID- 15450936
TI  - Biphasic induction of heme oxygenase-1 expression in macrophages stimulated with
      lipopolysaccharide.
AB  - Time course relationship between inductions of iNOS and HO-1 was evaluated in
      RAW264.7 macrophages stimulated with LPS. Expression of HO-1 mRNA increased in a
      biphasic pattern, but that of xCT (cystine transporter) and iNOS mRNA increased
      in a monophasic manner. HO-1 protein level increased also in a biphasic manner,
      at 1-2 h and again between 8 and 24 h. However, iNOS protein began to increase at
      4 h, quickly reaching a high level in a monophasic induction pattern. Production
      of NO* began to occur at 6 h and nitrite continued to accumulate in the culture
      medium. Total GSH level decreased markedly (50% of control) by 2 h, began to
      recover at 4 h, returned to control level by 6 h and increased above the control
      level during 10-24 h. Collectively, these results indicated that overproduced O2*
      depletes GSH and triggers induction of xCT, HO-1, iNOS and HO-1 expression in
      sequence. Most notably, the second-phase induction of HO-1 was caused by
      overproduced NO*, resulting from LPS-derived iNOS induction. When this iNOS
      derived delivery of NO* was combined with prior depletion of GSH using
      buthioninesulfoximine, an inhibitor of GSH biosynthesis, induction of HO-1 was
      potentiated. Furthermore, upon such super-induction of HO-1, NO* production was
      inhibited along with suppression of iNOS expression. Collectively, these results
      suggested that HO-1 is induced in a biphasic manner, sequentially by the
      overproduced O*2- and NO*, and the elevated HO-1 suppresses the production of
      these radicals in an auto-regulatory manner. This may allow the macrophages to
      survive from injuries that can be caused by concomitant oxidative and nitrosative
      stresses initiated by the LPS-driven oxidative burst.

PMID- 15450937
TI  - Investigation into the relationship between calyculin A-mediated potentiation of
      NADPH oxidase activity and inhibition of store-operated uptake of calcium by
      human neutrophils.
AB  - The primary objective of the current study was to investigate possible
      relationships between calyculin A (CA)-mediated potentiation of nicotinamide
      adenine dinucleotide phosphate (NADPH) oxidase activity and inhibition of store
      operated uptake of Ca2+ by chemoattractant-activated human neutrophils. Treatment
      of neutrophils with 100 nM CA, but not at lower concentrations (12.5-50 nM),
      prior to the addition of the N-formylated chemotactic tripeptide, N-formyl-L
      methionyl-L-leucyl-L-phenylalanine (FMLP) (1 microM), both potentiated and
      prolonged the activity of NADPH oxidase which was accompanied by exaggerated
      membrane depolarisation, delayed and attenuated membrane repolarisation, and
      inhibition of store-operated Ca2+ influx. Inclusion of diphenylene iodonium
      chloride (DPI, 10 microM), an inhibitor of NADPH oxidase, antagonised the effects
      of CA on NADPH oxidase activity and the membrane repolarisation responses of FMLP
      activated neutrophils, but failed to restore store-operated influx of Ca2+.
      Similarly, CA also inhibited store-operated influx of Ca2+ into FMLP-activated
      neutrophils from a patient with chronic granulomatous disease, a primary
      immunodeficiency disorder characterised by the absence of a functional NADPH
      oxidase. CA also inhibited the store-operated influx of Ca2+ into control
      neutrophils treated with 1 microM thapsigargin, a selective inhibitor of the
      endomembrane Ca2+-ATPase, which does not activate NADPH oxidase. Taken together,
      these observations demonstrate that augmentation of NADPH oxidase activity is not
      primarily involved in CA-mediated inhibition of the store-operated influx of Ca2+
      into activated human neutrophils.

PMID- 15450938
TI  - Differentiation-inducing quinolines as experimental breast cancer agents in the
      MCF-7 human breast cancer cell model.
AB  - The purpose of this work is to develop agents for cancer differentiation therapy.
      We showed that five antiproliferative quinoline compounds in the National Cancer
      Institute database stimulated cell differentiation at growth inhibitory
      concentrations (3-14 microM) in MCF-7 human breast tumor cells in vitro. The
      differentiation-inducing quinolines caused lipid droplet accumulation, a
      phenotypic marker of differentiation, loss of Ki67 antigen expression, a cell
      cycle marker indicative of exit into G0, and reduced protein levels of the G1--S
      transcription factor, E2F1. The antimalarial quinolines, chloroquine,
      hydroxychloroquine and quinidine had similar effects in MCF-7 cells, but were 3
      10 times less potent than the NSC compounds. NSC3852 and NSC86371 inhibited
      histone deacetylase (HDAC) activity in vitro and caused DNA damage and apoptosis
      in MCF-7 cells, consistent with their differentiation and antiproliferative
      activities. However, the HDAC assay results showed that for other compounds,
      direct HDAC enzyme inhibition was not required for differentiation activity. E2F1
      protein was suppressed by all differentiation quinolines, but not by non
      differentiating analogs, quinoline and primaquine. At equivalent
      antiproliferative concentrations, NSC69603 caused the greatest decrease in E2F1
      protein (90%) followed by antimalarials quinidine and hydroxychloroquine.
      NSC69603 did not cause DNA damage. The other NSC compounds caused DNA damage and
      apoptosis and reduced E2F1 levels. The physicochemical properties of NSC3852,
      NSC69603, NSC86371, and NSC305819 predicted they are drug candidates suitable for
      development as experimental breast tumor cell differentiation agents. We conclude
      DNA damage and reductions in E2F1 protein are mechanistically important to the
      differentiation and antiproliferative activities of these quinoline drug
      candidates.

PMID- 15450939
TI  - Geraniol and beta-ionone inhibit proliferation, cell cycle progression, and
      cyclin-dependent kinase 2 activity in MCF-7 breast cancer cells independent of
      effects on HMG-CoA reductase activity.
AB  - 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase catalyzes the formation
      of mevalonate, a precursor of cholesterol that is also required for cell
      proliferation. Mevalonate depletion results in a G1 phase cell cycle arrest that
      is mediated in part by impaired activity of cyclin-dependent kinase (CDK) 2, and
      decreased expression of positive regulators of G1 to S phase progression.
      Inhibition of mevalonate synthesis may, therefore, be a useful strategy to impair
      the growth of malignant cells. Plant isoprenoids, including beta-ionone and
      geraniol, have previously been shown to inhibit rodent mammary tumor development,
      and rodent and avian hepatic HMG-CoA reductase activity. We hypothesized that the
      putative anti-proliferative and cell cycle inhibitory effects of beta-ionone and
      geraniol on MCF-7 human breast cancer cells in culture are mediated by mevalonate
      depletion resulting from inhibition of HMG-CoA reductase activity. Flow
      cytometric analysis showed a G1 arrest in isoprenoid-treated MCF-7 cells, and
      also a G2/M arrest at higher concentrations of isoprenoids. These compounds
      minimally affected the growth of MCF-10F normal breast epithelial cells. Both
      beta-ionone and geraniol inhibited CDK 2 activity and dose-dependently decreased
      the expression of cyclins D1, E, and A, and CDK 2 and 4, without changing the
      expression of p21cip1 or p27kip1. Although both beta-ionone and geraniol also
      inhibited MCF-7 proliferation, only geraniol inhibited HMG-CoA reductase
      activity. While these effects were significantly correlated (r2=0.89, P <0.01),
      they were not causally related, since exogenous mevalonate did not restore growth
      in geraniol-inhibited cells. These findings indicate that mechanisms other than
      impaired mevalonate synthesis mediate the anti-proliferative and cell cycle
      regulatory effects of beta-ionone and geraniol in human breast cancer cells.

PMID- 15450940
TI  - Broad specificity of human phosphoglycerate kinase for antiviral nucleoside
      analogs.
AB  - Nucleoside analogs used in antiviral therapies need to be phosphorylated to their
      tri-phospho counterparts in order to be active on their cellular target. Human
      phosphoglycerate kinase (hPGK) was recently reported to participate in the last
      step of phosphorylation of cytidine L-nucleotide derivatives [Krishnan PGE, Lam
      W, Dutschman GE, Grill SP, Cheng YC. Novel role of 3-phosphoglycerate kinase, a
      glycolytic enzyme, in the activation of L-nucleoside analogs, a new class of
      anticancer and antiviral agents. J Biol Chem 2003;278:36726-32]. In the present
      work, we extended the enzymatic study of human PGK specificity to purine and
      pyrimidine nucleotide derivatives in both D- and L-configuration. Human PGK
      demonstrated catalytic efficiencies in the 10(4)-10(5)M(-1)s(-1) range for purine
      ribo-, deoxyribo- and dideoxyribonucleotide derivatives, either in D- or L
      configuration. In contrast, it was poorly active with natural pyrimidine D
      nucleotides (less than 10(3)M(-1)s(-1)). Pyrimidine L-enantiomers, which are
      promising therapeutic analogs against B hepatitis, were 2-25 times better
      substrates than their D-counterparts. The broad specificity of substrate of human
      PGK suggests that this enzyme may be involved in the cellular activation of
      several antiviral nucleoside analogs including dideoxyinosine, acyclovir, L-2'
      deoxycytosine and L-2'-deoxythymidine.

PMID- 15450941
TI  - Inhibition of repair of carboplatin-induced DNA damage by 9-beta-D
      arabinofuranosyl-2-fluoroadenine in quiescent human lymphocytes.
AB  - Previous studies including ours have demonstrated that DNA repair is one of the
      important targets of fludarabine. The aim of this study is to clarify a
      mechanistic interaction of carboplatin and F-ara-A, from the perspective of F-ara
      A-mediated inhibition of DNA repair initiated by carboplatin. Using human
      quiescent lymphocytes, we focused on DNA repair, since these cells provide a
      model of dormant cells. To evaluate the carboplatin-induced DNA incision and its
      repair, we used the alkaline comet assay. When lymphocytes were incubated with
      carboplatin, a dose-dependent increase in the tail-moment was observed. Then,
      tail-moment decreased in proportion to the incubation period in fresh media and
      recovered to the control level at 4 h. DNA rejoining was completely inhibited by
      F-ara-A at 10 microM through 0 to 6 h after washing out of these drugs and this F
      ara-A-induced inhibition was concentration-dependent. Cellular damage after drug
      exposure was evaluated with the induction of apoptosis as well as cytotoxic
      effect. Exposure to carboplatin alone did not induce any apparent cellular damage
      in quiescent lymphocytes. In contrast, a more than additive induction of
      apoptosis as well as an enhancement of cytotoxic action was observed in cells
      treated with a combination of carboplatin and F-ara-A. In the CEM cell line,
      there was no enhancement of the cytotoxic action of these drugs, despite the
      clear demonstration of an inhibitory effect on DNA repair. These results indicate
      that chemotherapy with carboplatin opened a new target for F-ara-A by initiating
      DNA repair in quiescent cells.

PMID- 15450942
TI  - Expression and biological effects of CB1 cannabinoid receptor in rat parotid
      gland.
AB  - Experiments were designed to determine whether cannabinoids affect salivary gland
      function. For this purpose, the effect of anandamide on cAMP accumulation,
      amylase release and Na+-K+-ATPase activity was studied in rat parotid glands.
      Anandamide induced a concentration-dependent increase in cAMP and led to amylase
      release but inhibited Na+-K+-ATPase activity. These effects were blocked by the
      CB1 cannabinoid receptor antagonist, AM281. The inhibition of adenylyl cyclase
      activity by SQ 22536 impaired amylase release and Na+-K+-ATPase inhibition. The
      effect of anandamide on cAMP accumulation significantly correlated with its
      action either on amylase release or on Na+-K+-ATPase activity. Such correlation
      strongly supports the view that the effect of anandamide on amylase release and
      Na+-K+-ATPase activity is the result of cAMP accumulation. The relative potencies
      of the CB1 cannabinoid receptor antagonist, AM281, to block these three
      functional responses were similar, supporting the view that anandamide actions in
      parotid glands were achieved through a single receptor subtype, the CB1. Binding
      studies using the selective cannabinoid CB1 receptor antagonist, [3H]SR141716A,
      indicated the presence of the specific binding site. It may be concluded that in
      parotid glands the endogenous cannabinoid anandamide, bound to the CB1
      cannabinoid receptor subtype, induces cAMP accumulation which in turn leads to
      amylase release and Na+-K+-ATPase inhibition.

PMID- 15450943
TI  - Inhibitory effects of epicatechin on interleukin-1beta-induced inducible nitric
      oxide synthase expression in RINm5F cells and rat pancreatic islets by down
      regulation of NF-kappaB activation.
AB  - Cytokines that are released by infiltrating inflammatory cells around the
      pancreatic islets are involved in the pathogenesis of type 1 diabetes mellitus.
      Specifically, interleukin-1beta (IL-1beta) stimulates inducible nitric oxide
      synthase (iNOS) expression and nitric oxide overproduction, leading to the beta
      cell damage. In activating this pathway, nuclear factor-kappaB (NF-kappaB) plays
      a crucial role, and many of the IL-1beta-sensitive genes contain NF-kappaB
      binding sites in their promoter regions. We have recently shown that epicatechin,
      which is a flavonoid, had a protective effect on pancreatic beta-cells in both
      streptozotocin-treated rats and islets. In the present study, the effects of
      epicatechin on IL-1beta-induced beta-cell damage were examined. RINm5F cells and
      islets were pretreated with epicatechin and next incubated with IL-1beta. The
      released nitrite, iNOS protein and mRNA expression levels were then measured.
      IkappaBalpha protein, nuclear translocation of NF-kappaB, and NF-kappaB DNA
      binding activity were also determined. Following the transient transfection of an
      iNOS promoter into the cells, the iNOS promoter activity was measured. ATP- or D
      glucose-induced insulin release was measured in RINm5F cells and islets,
      respectively. Epicatechin significantly reduced IL-1beta-induced nitrite
      production, iNOS protein and mRNA expressions, and it also inhibited IL-1beta
      induced IkappaBalpha protein degradation, NF-kappaB activation, and iNOS promoter
      activity. Epicatechin partly restored the IL-1beta-induced inhibition of insulin
      release. These results suggest that epicatechin inhibits the IL-1beta-induced
      iNOS expression by down-regulating NF-kappaB activation, and protecting beta
      cells from IL-1beta.

PMID- 15450944
TI  - Identification and importance of N-glycosylation of the human 5
      hydroxytryptamine3A receptor subunit.
AB  - We investigated the presence and potential role of N-glycosylation of the human
      (h) 5-hydroxytryptamine3 (5-HT3A) receptor subunit expressed in COS-7 cells.
      Incubation of cells with the N-glycosylation inhibitor, tunicamycin, reduced the
      molecular weight of the predominant immunoreactive h5-HT3A subunit species (from
      approximately 59 to 45 kDa) indicating that the h5-HT3A subunit is normally N
      glycosylated. Site-directed mutagenesis studies individually substituting four
      identified N-terminal asparagines (N5, N81, N147, N163) demonstrated that each
      expressed mutant displayed a reduced molecular weight (by approximately 3 kDa)
      suggesting that each asparagine residue was subject to N-glycosylation. In
      addition, 5-HT3 receptor binding studies indicated that prevention of N
      glycosylation, by individual amino acid substitution at each of the four
      asparagine residues, either prevented (N81, N147, N163) or greatly reduced (N5)
      the production of a 5-HT3 receptor binding site. Corresponding with the
      radioligand binding studies, immunocytochemical studies demonstrated that
      substitution of each asparagine either prevented (N81, N147, N163) or reduced
      considerably (N5) mutant protein expression within the cell membrane. The present
      study demonstrates an important role for N-glycosylation at multiple identified
      asparagine residues in the N-terminus of the h5-HT3A receptor subunit.

PMID- 15450945
TI  - Membrane permeation characteristics of abacavir in human erythrocytes and human T
      lymphoblastoid CD4+ CEM cells: comparison with (-)-carbovir.
AB  - Abacavir, (-)-(1S,4R)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2
      cyclopentene-1-methanol, is a novel purine carbocyclic nucleoside analogue that
      has been approved by the FDA for the treatment of HIV (as Ziagen trade mark
      [abacavir sulfate]). Chemically, abacavir and (-)-carbovir (CBV) differ only at
      the 6-position of the purine ring; abacavir contains a cyclopropylamino moiety in
      place of the 6-lactam functionality of CBV. Intracellularly both are ultimately
      metabolized to CBV triphosphate. We compared the membrane permeation
      characteristics of these two compounds at 20 degrees C in human erythrocytes and
      in human T-lymphoblastoid CD4+ CEM cells, using a "papaverine-stop" assay. In
      erythrocytes, abacavir influx was rapid, nonsaturable (rate constant=200
      pmol/s/mM/microl cell water), and unaffected by inhibitors of nucleoside or
      nucleobase transport. CBV influx was slow, saturable, strongly inhibited by
      adenine or hypoxanthine, and occurred via both the nucleobase carrier (Vmax=0.67
      pmol/s/microl cell water; Km=50 microM) and the nucleoside carrier (Vmax=0.47
      pmol/s/microl cell water; Km=440 microM). Similar qualitative results were
      obtained with CD4+ CEM cells, although CBV influx rates were somewhat higher and
      abacavir influx rates lower, compared to the corresponding rates in erythrocytes.
      Equilibrium studies further revealed that both compounds are concentrated
      intracellularly, but nonmetabolically, in both cell types, apparently due to
      cytosolic protein binding (absent in erythrocyte ghosts). We conclude that, in
      both cell types, while CBV influx is slow and carrier-dependent, abacavir influx
      occurs rapidly by nonfacilitated diffusion. The membrane permeation
      characteristics of abacavir are consistent with its superior oral bioavailability
      and its impressive ability to penetrate the central nervous system.

PMID- 15450946
TI  - Using yeast to screen for inhibitors of protein tyrosine phosphatase 1B.
AB  - Inhibition of protein tyrosine phosphatase 1B (PTP1B) has been proposed as a
      novel therapy to treat type 2 diabetes and obesity. In order to identify novel
      PTP1B inhibitors, we have developed a robust screen in Saccharomyces cerevisiae
      where growth is dependent on PTP1B catalytic activity. This was based on the
      observation that overexpression of v-Src, a tyrosine kinase, in yeast leads to
      lethality through mitotic dysfunction and this lethality can be reversed by co
      expression of PTP1B. The expression levels of v-Src and PTP1B were optimized to
      obtain a balance between robust growth and sensitivity to inhibitors. Screening
      was carried out in 96-well plates and growth of the liquid culture measured by
      absorbance at 600 nm. Initial characterization was performed using vanadate as
      well as some novel PTP1B inhibitors. Vanadate specifically inhibited PTP1B
      dependent growth in a dose dependent manner with an EC50 of 0.92 +/- 0.07 mM.
      This simple yeast growth interference assay has the potential for use as a high
      throughput screen for PTP1B inhibitors in sample collections or crude mixtures.

PMID- 15450947
TI  - The role of structural factors in the kinetics of cellular uptake of
      pyrazoloacridines and pyrazolopyrimidoacridines: implications for overcoming
      multidrug resistance towards leukaemia K562/DOX cells.
AB  - The appearance of multidrug resistance (MDR) of tumour cells to a wide array of
      antitumour drugs, structurally diverse and having different mechanisms of action,
      constitutes the major obstacle to the successful treatment of cancer. Our
      approach to search for non-cross resistant antitumour agents is based on the
      rational design of derivatives, which have a high kinetics of passive cellular
      uptake rendering their active efflux by MDR exporting pumps inefficient.
      Recently, two families of acridine cytotoxic agents were obtained,
      pyrazoloacridines (PACs) and pyrazolopyrimidoacridines (PPACs). The aim of this
      study was to examine molecular basis of the reported differences in retaining
      cytotoxic activity of these derivatives at cellular level against resistant
      erythroleukaemia K562/DOX (overexpressing P-glycoprotein) cell line. The study
      was performed using a spectrofluorometric method, which allows continuous
      monitoring of the uptake and efflux of fluorescent molecules by living cells. It
      was demonstrated that the presence of two additional rings, pyrazole and
      pyrimidine, fused to the acridine chromophore structure (PPAC) favoured more
      rapid cellular diffusion than the presence of only one additional pyrazole ring
      (PAC). The presence of hydrophobic substituent OCH3 markedly favoured the
      cellular uptake of pyrazoloacridines and pyrazolopyrimidoacridines while
      compounds having hydrophilic substituent OH exhibited very low kinetics of
      cellular uptake. In contrast, it was found that neither structure of the ring
      system nor the hydrophobic/hydrophilic character of examined substituents
      determined the rate of active efflux of these compounds by P-glycoprotein. Our
      data showed that a nearly linear relation exists between the resistance factor
      (RF) and lnV+ reflecting the impact of the cellular uptake rate (V+) on the
      ability of these compounds to overcome MDR.

PMID- 15450948
TI  - Effective metabolism and long intracellular half life of the anti-hepatitis B
      agent adefovir in hepatic cells.
AB  - Adefovir dipivoxil (ADV) is esterolytically cleaved to the 2'-deoxyadenosine
      monophosphate (dAMP) analog adefovir, subsequent phosphorylation leads to the
      formation of the anti-Hepatitis B virus (HBV) agent adefovir-DP. To better
      understand the mechanism of action of ADV, metabolism studies were done in Hep
      G2, Huh-7 and primary human hepatocytes. Separation of radiolabeled adefovir
      metabolites after incubation in Hep G2 cells suggested that adefovir in its mono-
      and di-phosphorylated forms are the only metabolites formed from adefovir.
      Incubation of 10 microM adefovir with hepatic cell lines and fresh monolayers of
      primary human hepatocytes from two donors and analysis of intracellular
      metabolites by liquid chromatography coupled to tandem mass spectrometry resulted
      in adefovir-DP levels of approximately 10 pmol/million cells. Adefovir was more
      efficiently phosphorylated in primary hepatocytes than cell lines with adefovir
      DP accounting for 44% versus 26% of total intracellular adefovir after 24 h.
      Egress studies showed adefovir-DP to have a half-life of 33 +/- 3 h, 10 +/- 1 h,
      48 +/- 3 h and 33 +/- 2 h in Hep G2, Huh-7, and primary hepatocytes from two
      separate donors, respectively. The markedly shorter half-life in Huh-7 cells was
      inferred to be transport dependent based on its sensitivity to the transport
      inhibitor MK-571. Effective phosphorylation coupled with a long intracellular
      half-life and small competing dATP pool sizes in primary hepatocytes forms the
      cellular metabolic basis for the efficacy of adefovir dipivoxil in the treatment
      of chronic hepatitis B.

PMID- 15450949
TI  - Cell-type specific calcium signaling by corticotropin-releasing factor type 1
      (CRF1) and 2a (CRF2(a)) receptors: phospholipase C-mediated responses in human
      embryonic kidney 293 but not SK-N-MC neuroblastoma cells.
AB  - The human corticotropin-releasing factor (hCRF) receptors CRF1 and CRF2(a) couple
      to the Gs protein. It has been postulated that CRF receptors may also signal
      through phospholipase C (PLC). To test this hypothesis, binding and signaling
      properties were determined for both receptor subtypes stably expressed in human
      embryonic kidney 293 (HEK293) and human SK-N-MC neuroblastoma cells. CRF
      receptors were highly expressed and strongly coupled to Gs in HEK293 and SK-N-MC
      cells. However, when the calcium mobilization pathway was investigated, marked
      differences were observed. In SK-N-MC cells, neither CRF receptor stimulated
      calcium mobilization in the fluorometric imaging plate reader (FLIPR) assay,
      whereas activation of orexin type 1 and 2 receptors stably expressed in SK-N-MC
      cells revealed robust calcium responses. In contrast, intracellular calcium was
      strongly mobilized by agonist stimulation of hCRF1 and hCRF2(a) receptors in
      HEK293 cells. In HEK293 cells, potency rank orders for calcium and cAMP responses
      were identical for both receptors, despite a rightward shift of the dose-response
      curves. Complete inhibition of calcium signaling of both hCRF1 and hCRF2(a)
      receptors was observed in the presence of the PLC inhibitor U-73,122 whereas
      ryanodine, an inhibitor of calcium release channels and the protein kinase A
      inhibitor Rp-cAMPS were ineffective. Finally, CRF agonists produced a small but
      significant stimulation of inositol 1,4,5-triphosphate (IP3) accumulation in
      hCRF1-and hCRF2(a)-transfected HEK293 cells. These data clearly show that
      phospholipase C-mediated signaling of CRF receptors is dependent upon the
      cellular background and that in HEK293 cells human CRF receptors robustly respond
      in the FLIPR format.

PMID- 15450950
TI  - Cadmium induces apoptotic cell death in WI 38 cells via caspase-dependent Bid
      cleavage and calpain-mediated mitochondrial Bax cleavage by Bcl-2-independent
      pathway.
AB  - Previous reports have demonstrated that cadmium (Cd) may induce cell death via
      apoptosis, but the mechanism responsible for cellular death is not clear. In this
      study, we investigated the signaling pathways implicated in Cd-induced apoptosis
      in lung epithelial fibroblast (WI 38) cells. Apoptotic features were observed
      using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling
      assay, propidium iodide staining and DNA laddering. A treatment of cadmium caused
      the caspase-8-dependent Bid cleavage, the release of cytochrome c (Cyt c),
      activation of caspase-9 and -3, and PARP cleavage. A caspase-8 specific inhibitor
      prevented the Bid cleavage, caspase-3 activation and cell death. Alternatively,
      we observed that full-length Bax was cleaved into 18-kDa fragment (p18/Bax); this
      was initiated after 12 h and by 36 h the full-length Bax protein was totally
      cleaved to the p18/Bax, which caused a drastic release of Cyt c from
      mitochondria. The p18/Bax was detected exclusively in the mitochondrial fraction,
      and it originated from mitochondrial full-length Bax, but not from the cytosol
      full-length Bax. Cd also induced the activation of the mitochondrial 30-kDa small
      subunit of calpain that was preceded by Bax cleavage. Cd induced the upregulation
      of Bcl-2 and the degradation of p53 protein. N-acetyl cysteine effectively
      inhibited the Cd-induced DeltaPsim reduction, indicating ROS acts upstream of
      mitochondrial membrane depolarization. Taken together, our results suggest that
      Cd-induced apoptosis was thought to be mediated at least two pathways; caspase
      dependent Bid cleavage, and the other is calpain-mediated mitochondrial Bax
      cleavage. Moreover, we found that the function of Bid and Bax was not dependent
      of Bcl-2, and that ROS can also contribute in the Cd-induced cell death.

PMID- 15450951
TI  - Effect of change in cellular GSH levels on mitochondrial damage and cell
      viability loss due to mitomycin c in small cell lung cancer cells.
AB  - The effect of GSH depletion on mitochondrial damage and cell death due to
      mitomycin c (MMC) was assessed in small cell lung cancer (SCLC) cells.
      Cytotoxicity of MMC was attenuated by Tempol and dicumarol, inhibitors of the
      enzymatic reduction, and increased by xanthine oxidase. The MMC-induced cell
      death and decrease in the GSH contents in SCLC cells were inhibited by caspase
      inhibitors (z-DQMD.fmk, z-IETD.fmk and z-LEHD.fmk) and antioxidants (N
      acetylcysteine, dithiothreitol and N-(2-mercaptopropionyl)glycine, melatonin,
      rutin and carboxy-PTIO). Thiol compounds, melatonin and rutin attenuated the MMC
      induced nuclear damage, decrease in mitochondrial transmembrane potential,
      release of cytochrome c and activation of caspase-3. Treatment of MMC caused a
      significant decrease in GSH contents in SCLC cells, which was followed by
      increase in the formation of reactive oxygen species. Depletion of GSH due to L
      buthionine sulfoximine enhanced the MMC-induced activation of caspase-3 and cell
      death in SCLC cells. Antioxidants, including N-acetylcysteine, depressed
      formations of nitric oxide, malondialdehyde and carbonyls due to MMC in SCLC
      cells. The results show that the reductive activation of MMC may cause cell death
      in SCLC cells by inducing mitochondrial dysfunction, leading to caspase-3
      activation, and by activation of caspase-8. The MMC-induced change in the
      mitochondrial membrane permeability, followed by cell death, in SCLC cells may be
      significantly enhanced by decrease in the intracellular GSH contents due to
      oxidative attack of free radicals.

PMID- 15450952
TI  - Oxidative DNA damage induced by a melatonin metabolite, 6-hydroxymelatonin, via a
      unique non-o-quinone type of redox cycle.
AB  - Melatonin, an indolic pineal hormone, is produced primarily at night in mammals
      and is important in controlling biological rhythms. Although melatonin is known
      to be effective as a free radical scavenger and has an anti-cancer effect,
      carcinogenic properties have also been reported. In relation to its carcinogenic
      potential, we have examined whether 6-hydroxymelatonin, a major melatonin
      metabolite, can induce DNA damage in the presence of metal ion using [32P]-5'-end
      labeled DNA fragments obtained from genes relevant to human cancer. 6
      Hydroxymelatonin induced site-specific DNA damage in the presence of Cu(II).
      Formamidopyrimidine-DNA glycosylase treatment induced cleavage sites mainly at G
      residues of the 5'-TG-3' sequence, whereas piperidine treatment induced cleavage
      sites at T mainly of 5'-TG-3'. Interestingly, 6-hydroxymelatonin strongly damaged
      G and C of the 5'-ACG-3' sequence complementary to codon 273 of the p53 gene.
      These results suggest that 6-hydroxymelatonin can cause double-base lesions. DNA
      damage was inhibited by both catalase and bathocuproine, Cu(I)-specific
      stabilizer, suggesting that reactive species derived from the reaction of H2O2
      with Cu(I) participate in DNA damage. Cytochrome P450 reductase efficiently
      enhanced 6-hydroxymelatonin-induced oxidative DNA damage and oxygen consumption,
      suggesting the formation of redox cycle. It is noteworthy that 6-hydroxymelatonin
      can efficiently induce DNA damage via non-o-quinone type of redox cycle.
      Formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), a characteristic
      oxidative DNA lesion, in calf thymus DNA was significantly increased by 6
      hydroxymelatonin in the presence of Cu(II). Furthermore, 6-hydroxymelatonin
      significantly increased the formation of 8-oxodG in human leukemia cell line HL
      60 but not in HP100, a hydrogen peroxide (H2O2)-resistant cell line derived from
      HL-60. The 6-hydroxymelatonin-induced 8-oxodG formation in HL-60 cells
      significantly decreased by the addition of bathocuproine or o-phenanthroline.
      Therefore, it is concluded that melatonin may exhibit carcinogenic potential
      through oxidative DNA damage by its metabolite.

PMID- 15450953
TI  - Anabolism of amdoxovir: phosphorylation of dioxolane guanosine and its 5'
      phosphates by mammalian phosphotransferases.
AB  - Amdoxovir [(-)-beta-D-2,6-diaminopurine dioxolane, DAPD], the prodrug of
      dioxolane guanosine (DXG), is currently in Phase I/II clinical development for
      the treatment of HIV-1 infection. In this study, we examined the phosphorylation
      pathway of DXG using 15 purified enzymes from human (8), animal (6), and yeast
      (1) sources, including deoxyguanosine kinase (dGK), deoxycytidine kinase (dCK),
      high Km 5'-nucleotidase (5'-NT), guanylate (GMP) kinase, nucleoside monophosphate
      (NMP) kinase, adenylate (AMP) kinase, nucleoside diphosphate (NDP) kinase, 3
      phosphoglycerate (3-PG) kinase, creatine kinase, and pyruvate kinase. In
      addition, the metabolism of 14C-labeled DXG was studied in CEM cells. DXG was not
      phosphorylated by human dCK, and was a poor substrate for human dGK with a high
      Km (7 mM). Human 5'-NT phosphorylated DXG with relatively high efficiency (4.2%
      of deoxyguanosine). DXG-MP was a substrate for porcine brain GMP kinase with a
      substrate specificity that was 1% of dGMP. DXG-DP was phosphorylated by all of
      the enzymes tested, including NDP kinase, 3-PG kinase, creatine kinase, and
      pyruvate kinase. The BB-isoform of human creatine kinase showed the highest
      relative substrate specificity (47% of dGDP) for DXG-DP. In CEM cells incubated
      with 5 microM DXG for 24 h, 0.015 pmole/10(6) cells (approximately 7.5 nM) of DXG
      TP was detected as the primary metabolite. Our study demonstrated that 5'
      nucleotidase, GMP kinase, creatine kinase, and NDP kinase could be responsible
      for the activation of DXG in vivo.

PMID- 15450954
TI  - In vitro metabolism of cyclosporine A by human kidney CYP3A5.
AB  - The objectives of this study were to characterize and compare the metabolic
      profile of cyclosporine A (CsA) catalyzed by CYP3A4, CYP3A5 and human kidney and
      liver microsomes, and to evaluate the impact of the CYP3A5 polymorphism on
      product formation from parent drug and its primary metabolites. Three primary CsA
      metabolites (AM1, AM9 and AM4N) were produced by heterologously expressed CYP3A4.
      In contrast, only AM9 was formed by CYP3A5. Substrate inhibition was observed for
      the formation of AM1 and AM9 by CYP3A4, and for the formation of AM9 by CYP3A5.
      Microsomes isolated from human kidney produced only AM9 and the rate of product
      formation (2 and 20 microM CsA) was positively associated with the detection of
      CYP3A5 protein and presence of the CYP3A5*1 allele in 4 of the 20 kidneys tested.
      A kinetic experiment with the most active CYP3A5*1-positive renal microsomal
      preparation yielded an apparent Km (15.5 microM) similar to that of CYP3A5 (11.3
      microM). Ketoconazole (200 nM) inhibited renal AM9 formation by 22-55% over a CsA
      concentration range of 2-45 microM. Using liver microsomes paired with similar
      CYP3A4 content and different CYP3A5 genotypes, the formation of AM9 was two-fold
      higher in CYP3A5*1/*3 livers, compared to CYP3A5*3/*3 livers. AM19 and AM1c9, two
      of the major secondary metabolites of CsA, were produced by CsA, AM1 and AM1c
      when incubated with CYP3A4, CYP3A5, kidney microsomes from CYP3A5*1/*3 donors and
      all liver microsomes. Also, the formation of AM19 and AM1c9 was higher from
      incubations with liver and kidney microsomes with a CYP3A5*1/*3 genotype,
      compared to those with a CYP3A5*3/*3 genotype. Together, the data demonstrate
      that CYP3A5 may contribute to the formation of primary and secondary metabolites
      of CsA, particularly in kidneys carrying the wild-type CYP3A5*1 allele.

PMID- 15450955
TI  - Molecular cloning of the monodehydroascorbate reductase gene from Brassica
      campestris and analysis of its mRNA level in response to oxidative stress.
AB  - In a majority of living organisms, a fundamental protection mechanism from
      reactive oxygen species is by the ascorbate-glutathione cycle in which an
      important antioxidant, ascorbate (vitamin C), is utilized to convert harmful H2O2
      to H2O. Monodehydroascorbate reductase (MDHAR) maintains reduced pools of
      ascorbate by recycling the oxidized form of ascorbate. By screening a Brassica
      campestris cDNA library, we identified a B. campestris MDHAR cDNA (BcMdhar) which
      encodes a polypeptide of 434 amino acids possessing domains characteristic of FAD
      and NAD(P)H-binding proteins. The predicted amino acid sequence of the open
      reading frame (ORF) shows a high level of identity to the cytosolic MDHAR of
      rice, pea and tomato, and does not possess N-terminal leader sequence suggesting
      that it encodes a cytosolic form of MDHAR. Genomic Southern blot analysis
      indicated that a single nuclear gene encodes this enzyme. Northern hybridization
      analysis detected BcMdhar transcripts in all plant tissues examined. The level of
      BcMdhar mRNA increased in response to oxidative stress invoked by hydrogen
      peroxide, salicylic acid, paraquat, and ozone.

PMID- 15450956
TI  - Mitochondrial alterations and apoptosis in smooth muscle from aged rats.
AB  - We studied changes in mitochondrial morphology and function in the smooth muscle
      of rat colon. Under confocal microscopy, tissues loaded with potentiometric dye
      displayed rapid and spontaneous depolarization. Cyclosporin A (CsA), inhibitor of
      the permeability transition pore (PTP), caused an increase in mitochondrial
      membrane potential (DeltaPsim) in tissues from adult young animals. In aged rats
      these changes were not observed. This suggests that physiological activation of
      PTP in aged rats is reduced. Electron microscopy showed alterations of the
      mitochondrial ultrastructure in tissues from aged rats involving a decreased
      definition of the cristae and fragmentation of the mitochondrial membranes. We
      also detected an increase in apoptotic cells in the smooth muscle from aged
      animals. Our results show that the aging process changes PTP activity, the
      ability to maintain DeltaPsim and mitochondrial morphology. It is suggested that
      these can be associated with mitochondrial damage and cell death.

PMID- 15450957
TI  - On the mechanism of mitochondrial permeability transition induction by
      glycyrrhetinic acid.
AB  - Glycyrrhetinic acid (GE), the aglycone of glycyrrhizic acid, a triterpene
      glycoside which represents one of the main constituents of licorice root, induces
      an oxidative stress in liver mitochondria responsible for the induction of
      membrane permeability transition. In fact, GE, by interacting with the
      mitochondrial respiratory chain, generates hydrogen peroxide which in turn
      oxidizes critical thiol groups and endogenous pyridine nucleotides leading to the
      opening of the transition pore. Most likely the reactive group of GE is the
      carbonyl oxygen in C-11 which, by interacting mainly with a Fe/S centre of
      mitochondrial complex I, generates an oxygen-centered radical responsible for the
      pro-oxidant action.

PMID- 15450958
TI  - Dimeric H+-ATP synthase in the chloroplast of Chlamydomonas reinhardtii.
AB  - H+-ATP synthase is the dominant ATP production site in mitochondria and
      chloroplasts. So far, dimerization of ATP synthase has been observed only in
      mitochondria by biochemical and electron microscopic investigations. Although the
      physiological relevance remains still enigmatic, dimerization was proposed to be
      a unique feature of the mitochondrion [Biochim. Biophys. Acta 1555 (2002) 154].
      It is hard to imagine, however, that closely related protein complexes of
      mitochondria and chloroplast should show such severe differences in structural
      organization. We present the first evidences for dimerization of chloroplast ATP
      synthases within the thylakoid membrane. By investigation of the thylakoid
      membrane of Chlamydomonas reinhardtii by blue-native polyacrylamide gel
      electrophoresis, dimerization of the chloroplast ATP synthase was detected.
      Chloroplast ATP synthase dimer dissociates into monomers upon incubation with
      vanadate or phosphate but not by incubation with molybdate, while the
      mitochondrial dimer is not affected by the incubation. This suggests a distinct
      dimerization mechanism for mitochondrial and chloroplast ATP synthase. Since
      vanadate and phosphate bind to the active sites, contact sites located on the
      hydrophilic CF1 part are suggested for the chloroplast ATP synthase dimer. As the
      degree of dimerization varies with phosphate concentration, dimerization might be
      a response to low phosphate concentrations.

PMID- 15450959
TI  - Higher plant-like subunit composition of mitochondrial complex I from
      Chlamydomonas reinhardtii: 31 conserved components among eukaryotes.
AB  - The rotenone-sensitive NADH:ubiquinone oxidoreductase (complex I) is the most
      intricate membrane-bound enzyme of the mitochondrial respiratory chain. Notably
      the bovine enzyme comprises up to 46 subunits, while 27 subunits could be
      considered as widely conserved among eukaryotic complex I. By combining proteomic
      and genomic approaches, we characterized the complex I composition from the
      unicellular green alga Chlamydomonas reinhardtii. After purification by blue
      native polyacrylamide gel electrophoresis (BN-PAGE), constitutive subunits were
      analyzed by SDS-PAGE coupled to tandem mass spectrometry (MS) that allowed the
      identification of 30 proteins. We compared the known complex I components from
      higher plants, mammals, nematodes and fungi with this MS data set and the
      translated sequences from the algal genome project. This revealed that the
      Chlamydomonas complex I is likely composed of 42 proteins, for a total molecular
      mass of about 970 kDa. In addition to the 27 typical components, we have
      identified four new complex I subunit families (bovine ESSS, PFFD, B16.6, B12
      homologues), extending the number of widely conserved eukaryote complex I
      components to 31. In parallel, our analysis showed that a variable number of
      subunits appears to be specific to each eukaryotic kingdom (animals, fungi or
      plants). Protein sequence divergence in these kingdom-specific sets is
      significant and currently we cannot exclude the possibility that homology between
      them exists, but has not yet been detected.

PMID- 15450960
TI  - Reductive titration of photosystem I and differential extinction coefficient of
      P700+ at 810-950 nm in leaves.
AB  - We describe a method of reductive titration of photosystem I (PSI) density in
      leaves by generating a known amount of electrons (e-) in photosystem II (PSII)
      and measuring the resulting change in optical signal as these electrons arrive at
      pre-oxidized PSI. The method complements a recently published method of oxidative
      titration of PSI donor side e- carriers P700, plastocyanin (PC) and cytochrome f
      by illuminating a darkened leaf with far-red light (FRL) [V. Oja, H. Eichelmann,
      R.B. Peterson, B. Rasulov, A. Laisk, Decyphering the 820 nm signal: redox state
      of donor side and quantum yield of photosystem I in leaves, Photosynth. Res. 78
      (2003) 1-15], presenting a nondestructive way for the determination of PSI
      density in intact leaves. Experiments were carried out on leaves of birch (Betula
      pendula Roth) and several other species grown outdoors. Single-turnover flashes
      of different quantum dose were applied to leaves illuminated with FRL, and the
      FRL was shuttered off immediately after the flash. The number of e- generated in
      PSII by the flash was measured as four times O2 evolution following the flash.
      Reduction of the pre-oxidized P700 and PC was followed as a change in leaf
      transmittance using a dual-wavelength detector ED P700DW (810 minus 950 nm, H.
      Walz, Effeltrich, Germany). The ED P700DW signal was deconvoluted into P700+ and
      PC+ components using the abovementioned oxidative titration method. The P700+
      component was related to the absolute number of e- that reduced the P700+ to
      calculate the extinction coefficient. The effective differential extinction
      coefficient of P700+ at 810-950 nm was 0.40+/-0.06 (S.D.)% of transmittance
      change per micromol P700+ m(-2) or 17.6+/-2.4 mM(-1) cm(-1). The result shows
      that the scattering medium of the leaf effectively increases the extinction
      coefficient by about two times and its variation (+/-14% S.D.) is mainly caused
      by light-scattering properties of the leaf.

PMID- 15450961
TI  - Responsibility of phosphatidylglycerol for biogenesis of the PSI complex.
AB  - Phosphatidylglycerol (PG) ubiquitous in thylakoid membranes of photosynthetic
      organisms was previously shown to contribute to accumulation of chlorophyll
      through analysis of the cdsA- mutant of a cyanobacterium Synechocystis sp.
      PCC6803 defective in PG synthesis (SNC1). Here, we characterized effects of
      manipulation of the PG content in thylakoid membranes of Synechocystis sp.
      PCC6803 on the photosystem complexes to specify roles of PG in biogenesis of
      thylakoid membranes. SNC1 cells with PG deprivation in vivo, together with the
      chlorophyll decrease, exhibited a decline not in PSII, but in PSI, at the complex
      level as well as the subunit levels. On the other hand, the decrease in the PSI
      complex was accounted for by a remarkable decrease in the PSI trimer with an
      increase in the monomer. These symptoms of SNC1 cells were complemented in vivo
      by supplementation of PG. Besides, a reduction in the PG content of thylakoid
      membranes isolated from the wild type in vitro on treatment with phospholipase A2
      (PLA2), similar to the PG-deprivation in SNC1 in vivo, brought about a decrease
      in the trimer population of PSI with accumulation of the monomer. These results
      demonstrated that PG contributes to the synthesis and/or stability of the PSI
      complex for maintenance of the cellular content of chlorophyll, and also to
      construction of the PSI trimer from the monomer at least through stabilization of
      the trimerized conformation.

PMID- 15450962
TI  - The mitochondrial respiratory chain of Ustilago maydis.
AB  - Ustilago maydis mitochondria contain the four classical components of the
      electron transport chain (complexes I, II, III, and IV), a glycerol phosphate
      dehydrogenase, and two alternative elements: an external rotenone-insensitive
      flavone-sensitive NADH dehydrogenase (NDH-2) and an alternative oxidase (AOX).
      The external NDH-2 contributes as much as complex I to the NADH-dependent
      respiratory activity, and is not modulated by Ca2+, a regulatory mechanism
      described for plant NDH-2, and presumed to be a unique characteristic of the
      external isozyme. The AOX accounts for the 20% residual respiratory activity
      after inhibition of complex IV by cyanide. This residual activity depends on
      growth conditions, since cells grown in the presence of cyanide or antimycin A
      increase its proportion to about 75% of the uninhibited rate. The effect of AMP,
      pyruvate and DTT on AOX was studied. The activity of AOX in U. maydis cells was
      sensitive to AMP but not to pyruvate, which agrees with the regulatory
      characteristics of a fungal AOX. Interestingly, the presence of DTT during cell
      permeabilisation protected the enzyme against inactivation. The pathways of
      quinone reduction and quinol oxidation lack an additive behavior. This is
      consistent with the competition of the respiratory components of each pathway for
      the quinol/quinone pool.

PMID- 15450963
TI  - Energetics of wild-type and mutant multidrug resistance secondary transporter
      LmrP of Lactococcus lactis.
AB  - LmrP, a proton/multidrug antiporter of Lactococcus lactis, transports a variety
      of cationic substrates. Previously, two membrane-embedded acidic residues, Asp142
      and Glu327, have been reported to be important for multidrug transport activity
      of LmrP. Here we show that neither Glu327 nor Asp142 is essential for ethidium
      binding but that Glu327 is a critical residue for the high affinity binding of
      Hoechst 33342. Substitution of these two residues, however, negatively influences
      the transport activity. The energetics of transport was studied of two closely
      related cationic substrates ethidium and propidium that carry one and two
      positive charges, respectively. Extrusion of monovalent ethidium is dependent on
      both the electrical membrane potential (Deltapsi) and transmembrane proton
      gradient (DeltapH), while extrusion of propidium predominantly depends on the
      DeltapH only. The LmrP mutants D142C and E327C, however, mediate electroneutral
      ethidium extrusion, but are unable to mediate DeltapH-dependent extrusion of
      propidium. These data indicate that Asp142 and Glu327 are involved in proton
      translocation.

PMID- 15450964
TI  - Dietary administration of sodium alginate enhances the immune ability of white
      shrimp Litopenaeus vannamei and its resistance against Vibrio alginolyticus.
AB  - Haemocyte count, phenoloxidase activity, respiratory burst (release of superoxide
      anion), superoxide dismutase (SOD) activity, glutathione peroxidase (GPX)
      activity, phagocytic activity and clearance efficiency to the pathogen Vibrio
      alginolyticus were measured in white shrimp Litopenaeus vannamei juveniles (12.3
      +/- 1.2 g) which had been fed diets containing sodium alginate at 0.5, 1.0, 2.0 g
      kg(-1) after five months. L. vannamei fed a diet containing 2.0 g kg(-1) sodium
      alginate had increased phenoloxidase activity, respiratory burst and SOD
      activity, but decreased GPX activity significantly. L. vannamei fed a diet
      containing 2.0 g kg(-1) sodium alginate had increased phagocytic activity and the
      shrimp fed a diet containing sodium alginate at 0.5, 1.0 or 2.0 g kg(-1) had
      increased clearance efficiency to V. alginolyticus. In another experiment, L.
      vannamei, which had been fed control diet, or sodium alginate-containing diets
      after 5 months, were challenged with V. alginolyticus at 2 x 10(6) colony-forming
      units (CFU) shrimp(-1) and then placed in seawater of 15 per thousand. The
      survival of shrimp fed a diet containing 2.0 g kg(-1) after one day, and the
      survival of shrimp fed diets containing sodium alginate at 0.5 and 1.0 g kg(-1)
      after 2-4 days increased significantly, as compared to that of shrimp fed control
      diet. It is therefore concluded that administration of sodium alginate in the
      diet at 2.0 g kg(-1) or less could enhance the immune ability of L. vannamei and
      increase its resistance to V. alginolyticus infection.

PMID- 15450965
TI  - Protection against Atlantic halibut nodavirus in turbot is induced by recombinant
      capsid protein vaccination but not following DNA vaccination.
AB  - Fish nodaviruses (betanodaviruses) are small, non-enveloped icosahedral single
      stranded positive-sense RNA viruses that can cause viral encephalopathy and
      retinopathy (VER) in a number of cultured marine teleost species, including
      Atlantic halibut (Hippoglossus hippoglossus). A recombinant protein vaccine and a
      DNA vaccine were produced, based on the same capsid-encoding region of the
      Atlantic halibut nodavirus (AHNV) genome, and tested for protection in juvenile
      turbot (Scophthalmus maximus). Vaccine efficacy was demonstrated in the fish
      vaccinated with recombinant capsid protein but not in the DNA-vaccinated fish,
      despite the fact that in vivo expression of the DNA vaccine-encoded antigen was
      confirmed by RNA in situ hybridisation and immunohistochemistry. Combined DNA and
      recombinant vaccine administration did not improve the effect of the latter.
      Surprisingly, fish vaccinated with 50 microg recombinant protein demonstrated a
      threefold lower survival rate than the two groups that received 10 microg
      recombinant protein. Neither the recombinant protein vaccine nor the DNA vaccine
      induced anti-viral antibodies 9 weeks after immunisation, while antibodies
      reactive with the recombinant protein were detectable mainly in fish vaccinated
      with 50 microg recombinant protein. The study also demonstrates evidence of viral
      replication inside the myocytes of intramuscularly challenged fish.

PMID- 15450966
TI  - Influence of vaccination on the nitric oxide response of gilthead seabream
      following infection with Photobacterium damselae subsp. piscicida.
AB  - The nitric oxide (NO) response of vaccinated and non-vaccinated juvenile gilthead
      seabream was studied in vivo and the NO response of isolated kidney macrophages
      of fish was studied in vitro. Fish were vaccinated with formalin-killed
      Photobacterium damselae subsp. piscicida (Pdp) with or without Freund's
      incomplete adjuvant (FIA) and control fish received phosphate buffered saline
      (PBS). Thirty days later, fish were injected with a sublethal dose of Pdp and 3
      fish/group were bled at time periods thereafter and serum nitrite and citrulline
      levels were determined as a measure of the NO response. All infected groups
      showed an increase in NO metabolites from 6h to 27 days, with peak levels at 24
      h. However, the response in bacterin-vaccinated fish was significantly higher
      than in the non-vaccinated group and the bacterin plus FIA resulted in a further
      significant enhancement. Similarly enhanced NO responses were produced in vitro
      by isolated macrophages obtained from vaccinated compared with non-vaccinated
      fish 30 days after vaccination following infection, with the response in
      macrophages from fish vaccinated with the bacterin plus FIA being significantly
      higher than those from fish vaccinated with the bacterin alone. Thus, vaccination
      resulted in an enhanced NO response to infection with Pdp in vivo and in vitro.
      Furthermore, the level of protection of fish to experimental challenge with
      virulent Pdp correlated with the level of the NO responses in the different
      groups.

PMID- 15450967
TI  - Peptidoglycan inducible expression of a serine proteinase homologue from kuruma
      shrimp (Marsupenaeus japonicus).
AB  - A cDNA encoding a serine proteinase homologue of kuruma shrimp (Marsupenaeus
      japonicus) was cloned. The 1257 bp cDNA encodes a 339 amino acid putative
      peptide, with a signal sequence of 16 amino acid residues. The deduced amino acid
      sequence is 42-67% similar to the immune-related serine proteinases and serine
      proteinase homologues of arthropods. It contains catalytic triad residues in the
      putative catalytic domain except for one substitution of Ser by a Gly residue.
      The six cysteine residues that form three disulphide bridges in most serine
      proteinases were conserved. The M. japonicus serine proteinase homologue was
      mainly expressed in haemocytes, in which expression dramatically increased after
      3 days feeding with peptidoglycan at 0.2 mg kg(-1) shrimp body weight per day.

PMID- 15450968
TI  - The ontogeny of MHC class I expression in rainbow trout (Oncorhynchus mykiss).
AB  - In the present study, clonal rainbow trout (Oncorhynchus mykiss) embryos and
      larvae were assayed for the expression of key molecules involved in specific cell
      mediated cytotoxicity using an anti-MHC class I monoclonal Ab and by RT-PCR using
      specific primers derived from classical MHC class I (class Ia), TCR and CD8.
      Whereas RT-PCR revealed that MHC class Ia and CD8 were expressed from at least 1
      week after fertilisation (p.f.) on, TCR expression was detectable from 2 weeks
      p.f. Immunohistochemistry indicated an early and distinct expression of MHC class
      I protein in the thymus. Positive lymphoid, epithelial and endothelial cells were
      found in the pronephros, in the spleen and in the inner and outer epithelia at
      later stages. Whereas in older rainbow trout the intestine is counted among the
      organs of the highest class I expression, during ontogeny it was the last site
      (39 days after hatching) where such expression was detectable. Knowledge on the
      appearance of the assayed key molecules during fish development is relevant for
      the pathogenesis of infections as well as for early vaccine delivery. Besides
      such information regarding the development of the adaptive immune system,
      immunohistochemistry revealed that in early larvae MHC class I was expressed in
      neurons whereas in older rainbow trout this was not observed.

PMID- 15450969
TI  - Purification and characterization of phenoloxidase from clam Ruditapes
      philippinarum.
AB  - Using L-dihydroxyphenylalanine (L-DOPA) as a specific substrate, phenoloxidase
      (PO) from clam (Ruditapes philippinarum) was purified by Q Sepharose Fast Flow
      ion-exchange chromatography and Sephacryl S-100 gel-filtration, and characterized
      biochemically and enzymatically in this study. The molecular mass of PO in SDS
      PAGE is about 76.9 kDa, and the prophenoloxidase (proPO) molecule, isolated as a
      monomeric protein, is 84.1 kDa. The PO molecule had a high oxidative activity,
      and the proPO molecule had almost no oxidative activity. The PO activity was
      optimal at pH 7.0 and temperature of 40 degrees C. The Km value of the PO for L
      DOPA was 2.2 mmol l(-1). The PO was extremely sensitive to benzoic acid and
      sodium sulfite, very sensitive to citric acid, thio urea, 1-phenyl-2-thiourea and
      cysteine, but not sensitive to ascorbic acid. Combined with its specific enzyme
      activity on tyrosine and L-DOPA, it can be concluded that the Ruditapes PO is
      probably a kind of tyrosinase-type phenoloxidase. The PO activity was strongly
      inhibited by ethylenediaminetetraacetic acid (EDTA), diethyldithiocarbamate
      (DETC), Zn2+, Ca2+ and Cu2+, as well as by Mg2+. The results with EDTA, DETC, and
      some metal ions, combined with the perfect recovery effect of Cu2+ on DETC
      inhibited PO activity, indicate that Ruditapes PO is most probably a copper
      containing metalloenzyme.

PMID- 15450970
TI  - In vivo effects of propolis, a honeybee product, on gilthead seabream innate
      immune responses.
AB  - The potential effect of the intraperitoneal or dietary administration of
      propolis, a honeybee product, on gilthead seabream (Sparus aurata L.) innate
      immune responses was evaluated. Fish were intraperitoneally injected with 5mg of
      water (WEP), ethanol (EEP) or both (WEP + EEP) extracts of propolis and sampled
      after 1, 3, 5 and 10 days. When administered in the diet, propolis was dissolved
      in ethanol and added to a pellet diet at a concentration of 0, 0.1 or 10 g kg(-1)
      diet, the fish being sampled after 1, 2, 4 and 6 weeks of feeding. Humoral
      (alternative complement activity and peroxidase content) and cellular (leucocyte
      peroxidase, phagocytosis, cytotoxicity and respiratory burst activity) immune
      responses were evaluated in both cases. The results suggest that propolis has
      limited immunostimulatory effects although intraperitoneal administration was
      more effective than dietary intake. The effects that were noted were at cellular
      level, namely, phagocytosis and cytotoxicity.

PMID- 15450971
TI  - Kinetics of Mx expression in rainbow trout (Oncorhynchus mykiss) and Atlantic
      salmon (Salmo salar L.) parr in response to VHS-DNA vaccination.
AB  - The duration of the Mx mRNA response to an intramuscular injection of the viral
      haemorrhagic septicaemia virus (VHSV) glycoprotein (G) gene DNA vaccine as well
      as to the control plasmid was determined in rainbow trout at 14 degrees C over a
      period of 11 weeks. The Mx response was detectable on day 7, peaked on day 14 and
      returned to pretreatment levels on day 21 and thereafter. No increase in Mx
      expression was detectable to the control plasmid. In further experiments, the
      kinetics of the Mx response were compared in rainbow trout and Atlantic salmon
      parr kept at 10 degrees C and injected with the DNA vaccine or the synthetic
      double-stranded RNA, poly I:C. In both species there was a rapid response to poly
      I:C detectable from day 1, reaching maximum from days 3 to 9 and decreasing to
      background level by day 12. The peak level and return to background was reached
      slightly later in salmon. In both species the response to the VHS/DNA vaccine was
      slower to begin, not being detectable on days 1 and 3, but elevated levels were
      found on day 6. However, in the salmon parr, the peak level was on day 6 and the
      signal disappeared by day 12, while in the rainbow trout, the response peaked at
      day 12 and lasted until day 21. The kinetics of the Mx response to the VHS/DNA
      vaccine in rainbow trout correlate with the early non-specific protection against
      VHS in this species following vaccination. It is speculated that the more
      transient Mx response in Atlantic salmon parr to the DNA vaccine may be related
      to the innate resistance of salmon to VHS.

PMID- 15450972
TI  - Assessment of snapper (Pagrus auratus) natural IgM binding to bromelain treated
      sheep erythrocytes.
AB  - Normal snapper (Pagrus auratus Bloch and Schneider) serum was examined for
      natural IgM that binds to protease (bromelain) treated sheep erythrocytes
      (BrSRBC) in a model assay system that has been used to appraise natural IgM of
      various mammals. Normal snapper serum lysed BrSRBC while haemolysis was abrogated
      by heat inactivation of serum and in divalent cation-deficient conditions,
      indicative of classical complement mediated lysis. In addition, heat inactivated
      normal snapper serum agglutinated BrSRBC while phosphatidylcholine (PtC)
      liposomes partially inhibited both haemolysis and agglutination. Inhibition of
      haemolysis and agglutination may have been mediated by an interaction between
      immunoglobulin (Ig) and PtC as protein A purified snapper Ig bound to PtC
      liposomes. However it is not known if this binding was PtC specific nor if the
      binding was initiated by either the Fab and/or Fc domains of snapper Ig. BrSRBC
      plaque forming cells (PFC) were detected in the peritoneal cavity, spleen, head
      kidney and peripheral blood of normal snapper. The greatest proportion of BrSRBC
      PFC per B cell was within the peritoneal cavity followed by the spleen,
      peripheral blood and head kidney. Together, these data suggest that normal
      snapper serum may contain natural Ig that binds BrSRBC, activating the classical
      complement cascade.

PMID- 15450973
TI  - Noc-king out exocrine and endocrine secretion.
AB  - The Rab GTPase effector Noc2 was brought into the limelight by a recent
      publication that demonstrated its requirements at different stages of regulated
      exocytosis. Noc2 knockout resulted in distinct abnormalities in endocrine and
      exocrine cells, ranging from the accumulation of secretory granules of increased
      size to impairments in the regulated release of their secretory products.
      Explanations for these defects are beginning to emerge and they promise to reveal
      some of the most jealously kept secrets of regulated exocytosis.

PMID- 15450974
TI  - The glideosome: a molecular machine powering motility and host-cell invasion by
      Apicomplexa.
AB  - The apicomplexans are obligate intracellular protozoan parasites that rely on
      gliding motility for their migration across biological barriers and for host-cell
      invasion and egress. This unusual form of substrate-dependent motility is powered
      by the "glideosome", a macromolecular complex consisting of adhesive proteins
      that are released apically and translocated to the posterior pole of the parasite
      by the action of an actomyosin system anchored in the inner membrane complex of
      the parasite. Recent studies have revealed new insights into the composition and
      biogenesis of Toxoplasma gondii myosin-A motor complex and have identified an
      exciting set of small molecules that can interfere with different aspects of
      glideosome function.

PMID- 15450975
TI  - Bacterial cell polarity: a "swarmer-stalked" tale of actin.
AB  - The actin cytoskeleton is important for cell polarity and morphogenesis in
      eukaryotic organisms. A recent article describes an unexpected requirement for
      the actin-like protein MreB in the polarization of the bacterium Caulobacter
      crescentus. More surprisingly, the formation of a filamentous MreB structure that
      traverses the length of the cell is sufficient for randomized polar localization
      of cell-fate proteins. In this article, we discuss the significance of these
      findings and the possible mechanisms by which an actin-like cytoskeleton could
      mediate cell polarity in bacteria.

PMID- 15450976
TI  - The mechanism, function and regulation of depolymerizing kinesins during mitosis.
AB  - Kinesins are motor proteins that use the hydrolysis of ATP to do mechanical work.
      Most of these motors translocate cargo along the surface of the microtubule (MT).
      However, a subfamily of these motors (Kin-I kinesins) can destabilize MTs
      directly from their ends. This distinct ability makes their activity crucial
      during mitosis, when reordering of the MT cytoskeleton is most evident. Recently,
      much work has been done to elucidate the structure and mechanism of
      depolymerizing kinesins, particularly those of the mammalian kinesin mitotic
      centromere-associated kinesin (MCAK). In addition, new regulatory factors have
      been discovered that shed light on the regulation and precise role of Kin-I
      kinesins during mitosis.

PMID- 15450977
TI  - Karyopherins: from nuclear-transport mediators to nuclear-function regulators.
AB  - The karyopherin beta (or importin beta) family comprises soluble transport
      factors that mediate the movement of proteins and RNAs between the nucleus and
      cytoplasm. Recent studies have extended the role of karyopherins to regulating
      assembly of the nuclear pore complex (NPC), assembly of the nuclear envelope,
      mitosis and replication. New data also address how karyopherins specifically
      recognize and transport many distinct cargoes and traverse the NPC. These data
      raise the possibility that, although there might be a universal mechanism for
      nuclear transport, specific interactions between karyopherins and components of
      the NPC might function to regulate differentially the ability of the different
      karyopherins to cross the NPC.

PMID- 15450978
TI  - Diversity in immune-cell interactions: states and functions of the immunological
      synapse.
AB  - The contact-dependent exchange of signals between epithelial and neuronal cells
      results from close membrane-membrane appositions, which are stabilized for years
      by polarized adhesion, cytoskeletal assemblies and extracellular scaffold
      proteins. By contrast, owing to a lack of scaffold proteins, interactions between
      immune cells such as T lymphocytes and antigen-presenting cells (APCs) comprise a
      spectrum of structurally diverse and short-lived interaction modes that last from
      minutes to hours. Signals exchanged between T cells and APCs are generated in a
      specific contact region, termed the "immunological synapse", that coordinates
      cytoskeletal dynamics with the T-cell receptor (TCR), the engagement of accessory
      receptors and membrane-proximal signaling. Recent data shed light on the
      different physical and molecular interaction modes that occur between T cells and
      APCs, including their dynamics and transition stages, and their consequences for
      signaling, activation and T-cell effector function.

PMID- 15450979
TI  - Membrane-protein integration and the role of the translocation channel.
AB  - Most eukaryotic membrane proteins are integrated into the lipid bilayer during
      their synthesis at the endoplasmic reticulum (ER). Their integration occurs with
      the help of a protein-conducting channel formed by the heterotrimeric Sec61
      membrane-protein complex. The crystal structure of an archaeal homolog of the
      complex suggests mechanisms that enable the channel to open across the membrane
      and to release laterally hydrophobic transmembrane segments of nascent membrane
      proteins into lipid. Many aspects of membrane-protein integration remain
      controversial and poorly understood, but new structural data provide testable
      hypotheses. We propose a model of how the channel recognizes transmembrane
      segments, orients them properly with respect to the plane of the membrane and
      releases them into lipid. We also discuss how the channel would prevent small
      molecules from crossing the lipid bilayer while it is integrating proteins.

PMID- 15450980
TI  - Building a retinal mosaic: cell-fate decision in the fly eye.
AB  - Across the animal kingdom, color discrimination is achieved by comparing the
      outputs of photoreceptor cells (PRs) that have different spectral sensitivities.
      Much remains to be understood about how the pattern of these different PRs is
      generated and maintained. The Drosophila eye has long provided a beautiful system
      for understanding various aspects of retinal-cell differentiation. Recent
      progress in this field is revealing that a highly ordered series of events,
      involving cell-cell communication, localized signaling and stochastic choices,
      creates a complex mosaic of PRs that is reminiscent of the human retina. Notably,
      several of the factors used in generating the retinal mosaic of the fruitfly have
      corresponding functions in vertebrates that are likely to have similar roles.

PMID- 15450981
TI  - Guenther Gerisch and Dictyostelium, the microbial model for ameboid motility and
      multicellular morphogenesis.
AB  - Beginning in 1960 and continuing to this day, Guenther Gerisch's work on the
      social ameba Dictyostelium discoideum has helped to make it the model organism of
      choice for studies of cellular activities that depend upon the actomyosin
      cytoskeleton. Gerisch has brought insight and quantitative rigor to cell biology
      by developing novel assays and by applying advanced genetic, biochemical and
      microscopic techniques to topics as varied as cell-cell adhesion, chemotaxis,
      motility, endocytosis and cytokinesis.

PMID- 15450982
TI  - Eight fundamental unsolved problems in sarcoidosis.
AB  - More than 100 years since the identification and characterization of sarcoidosis,
      its etiology, fundamental nature, pathogenesis, incidence, ethnic predilections,
      relationship to the Kveim test and prognostic determinants remain largely either
      unknown or unexplained, and treatment indications, absent compelling findings,
      remain undefined. Professor Hilbert's "Address" delineates these fundamental
      deficits in our knowledge and understanding.

PMID- 15450983
TI  - ICU management of severe acute pancreatitis.
AB  - In intensive care medicine, severe acute pancreatitis (SAP) remains a very
      challenging disease with multiple complications and high mortality. The main
      pathophysiological mechanisms determining outcome are an uncontrolled systemic
      hyperinflammatory response early on and infection of pancreatic necrosis later on
      in the disease process. Despite a better understanding in recent years of the
      mechanisms and the mediators involved in the hyperinflammatory response, there
      is, as yet, no generally recognized specific treatment for this disease. Since
      early identification and aggressive treatment of associated organ dysfunction can
      have a major impact on outcome, early assessment of prognosis and severity is
      important. The evidence available indicates that patients with severe acute
      pancreatitis do not benefit from therapy with available antisecretory drugs or
      protease inhibitors. Supportive therapy, such as vigorous hydration, analgesia,
      correction of electrolyte and glycemia disorders, and pharmacological or
      mechanical support targeted at specific organs, is still the mainstay of therapy.
      In spite of meager evidence, prophylactic antibiotics with good penetration in
      pancreatic tissue are recommended in severe acute pancreatitis. Enteral nutrition
      via a nasojejunal tube has become the preferred route of feeding. Most patients
      with sterile necrosis do not benefit from surgical intervention. In patients with
      proven infection of pancreatic tissue, surgery is necessary. Percutaneous,
      radiological drainage techniques may eventually become an alternative form of
      drainage in selected patients.

PMID- 15450984
TI  - The internal medicine clinical clerkship: opportunities for improvement.
AB  - We have witnessed a recent explosion of new knowledge in medical education. The
      use of creative teaching methodologies, curriculum development and the
      recognition of medical education as a field ripe for research and investigation
      have occurred at many medical schools in Europe and North America. However, most
      of this innovation has occurred in the pre-clinical years and very little has
      been transferred to the clinical setting. The use of comprehensive curricula with
      goals and objectives, problem-based learning (PBL), a renewed emphasis on
      physical diagnosis, evidence-based medicine (EBM), patient-centered interviewing,
      ambulatory education, computer-based learning and new methods of assessment all
      need to be introduced into the clinical clerkships while ensuring that the
      majority of learning still takes place through the student-patient interaction at
      the bedside. By virtue of its traditional excellence in medical education,
      internal medicine has the opportunity to take the lead in revitalizing clinical
      education by building on our successful past and leading the other disciplines
      into the future.

PMID- 15450985
TI  - Medical imaging in nephropathia epidemica and their clinical correlations.
AB  - BACKGROUND: This study was designed to evaluate radiological findings in chest
      and sinus radiographs and renal ultrasound (US) in patients with nephropathia
      epidemica (NE) and to determine whether changes in these medical images are
      related to each other or to the clinical course of NE. METHODS: Radiological
      findings and clinical course were studied in 380 hospital-treated NE patients
      during the years 1982-1998. RESULTS: In 35% of the patients there were clear
      changes in chest radiographs. Pleural effusion, atelectasis, and interstitial
      infiltration were the most common X-ray findings. Forty-seven percent had changes
      in renal US, with increased cortical echoicity and cortical swelling being the
      most common findings. Thirty-three percent of the patients with clinical symptoms
      of sinusitis had changes in sinus radiographs. Abnormal findings on chest
      radiographs were clearly associated with fluid volume overload, high blood
      pressure level, leukocytosis, degree of clinical renal insufficiency, and
      thrombocytopenia. Abnormal findings in renal US were associated to some extent
      with fluid volume overload and degree of clinical renal insufficiency.
      CONCLUSIONS: Some 35% of patients had clear changes in chest radiographs and 47%
      showed changes in renal US. Abnormal findings in chest radiographs were clearly
      associated, and abnormal findings in renal US were associated to some extent,
      with the severity of the clinical course of NE.

PMID- 15450986
TI  - The significance of human platelet-activating factor-acetylhydrolase in patients
      with chronic stable angina.
AB  - BACKGROUND: Inflammatory reactions within coronary atherosclerotic plaques are
      increasingly thought to be crucial determinants of the clinical course in
      patients with coronary artery disease (CAD). Platelet-activating factor
      acetylhydrolase (PAF-AH) is considered to reflect the ongoing inflammatory
      process in patients with CAD. Our objective was to determine the activity of PAF
      AH in patients with stable angina and its correlations to lipoprotein levels and
      the inflammatory status of the patient. METHODS: Forty-five patients with
      documented CAD and stable angina and 20 controls were investigated for PAF-AH
      activity, lipoprotein levels, and peripheral neutrophil (PMN) activity. RESULTS:
      Patients were divided into two groups according to the values of PAF-AH activity
      (group 1: </=250 IU/l and group 2: >250 IU/l). A correlation was observed between
      PAF-AH activity and LDL-C and HDL-C in controls and in all patients. The
      percentage of granulocytes generating intracellular O(2)(-) in unstimulated PMN
      was higher in group 2 patients than in group 1 patients and controls. The
      phagocytic activity of PMNs had an inverse correlation with PAF-AH in group 2.
      High intracellular O(2)(-) generation was coupled with low extracellular release
      of the anion and phagocytosis impairment in group 2. During the follow-up period,
      some of the patients in group 2 displayed a worsening of the clinical state
      and/or resting ECG changes. CONCLUSIONS: PAF-AH activity in patients with stable
      angina is correlated with hyperlipemia and a high PMN activation state, and it
      may be considered a potential predictor of vascular risk.

PMID- 15450987
TI  - Time trends in three triennial surveys of cardiovascular risk factors and their
      treatment among patients discharged from divisions of internal medicine The FAPOI
      1, FADOI-2, and FADOI-3 studies.
AB  - BACKGROUND: There is increasing interest in monitoring cardiovascular risk factor
      levels and their treatment. We decided to study this in patients discharged from
      Divisions of Internal Medicine. METHODS: In three studies conducted in 1996,
      1999, and 2002, data was collected on diagnoses of cardiovascular diseases and
      cardiovascular risk factor levels and treatment in 5904, 7476, and 9649 patients,
      respectively, aged 35 years or older, who were discharged within a week from 235,
      345, and 517 Divisions of Internal Medicine in Italy. RESULTS: Between the first
      and third surveys, a relative decrease in atherosclerotic cardiovascular diseases
      was recorded, but heart failure showed a definite increase, reaching 11% of all
      cases. Mean levels of most cardiovascular risk factors decreased significant;
      only obesity did not. The proportion of treated hypertensives increased slightly
      (from 65% to 83% among men, and from 69% to 85% among women). The proportion of
      controlled hypertensives also rose, reaching around 37%. The proportion of
      treated dyslipidemics increased from 10% to 28% in men and from 12% to 25% in
      women, due to an increase in the use of statins. CONCLUSIONS: It is essential to
      focus attention on cardiovascular risk factors in order to optimize their
      treatment and to reduce cardiovascular disease.

PMID- 15450988
TI  - Diagnosis of deep venous thrombosis and alternative diseases in symptomatic
      outpatients.
AB  - BACKGROUND: The management of patients with suspected deep vein thrombosis (DVT)
      is controversial. Recent studies have suggested that anticoagulant treatment can
      safely be withheld if the clinical probability is low and the D-dimer
      concentration in blood is normal. We examined a diagnostic algorithm comparing a
      score-based, explicit assessment model with our empirical, implicit approach,
      which was designed to be more sensitive for distal DVT. We further investigated
      what information would be lost by not performing a routine ultrasound examination
      in each patient. METHODS: Consecutive patients with suspected DVT first received
      a D-dimer estimation, then an examination to assess the clinical probability, and
      ultimately objective testing for DVT or alternative diseases. Ultrasound was used
      in all patients; venography and other tests were performed as indicated. The
      implicit assessment of clinical probability was compared with the explicit
      scoring system of Wells et al., and the value of ultrasound was assessed
      retrospectively. RESULTS: In 57 of 206 patients (28%), DVT was confirmed. A high
      clinical probability was attributed to all pelvic and femoral DVT (except one),
      but popliteal and crural DVT were missed in 78% by the explicit approach and in
      34% by the implicit approach. The negative predictive values for any DVT were 83%
      for the explicit assessment and 92% for the implicit assessment, 95% for the D
      dimer estimation, and 98% (95% CI 92-99) for the combination of low implicit
      clinical probability and a negative D-dimer test. This combination yielded the
      same NPV for isolated crural DVT and was found in 41% of all suspected cases. An
      alternative organic diagnosis was established in 100 patients (48%) and no
      organic diagnosis was made in 49 (24%). In half of all suspected cases,
      irrespective of whether DVT was present or not, concomitant or alternative venous
      pathologies were observed. Ultrasound was found useful in 91% of cases.
      CONCLUSIONS: Proximal as well as distal DVT can reliably be excluded when both a
      sensitive assessment of clinical probability and a bedside D-dimer assay are
      negative. Nevertheless, ultrasound is helpful in establishing alternative
      diagnoses. Strategies to reduce the number of ultrasound investigations appear to
      lack comprehensiveness.

PMID- 15450989
TI  - Sickle cell trait and gender influence type 2 diabetic complications in African
      patients.
AB  - BACKGROUND: Black and African patients with type 2 diabetes have a greater
      frequency and more severe vascular complications of the disease, even after
      correction for socioeconomic factors. Asymptomatic sickle cell trait (SCT;
      hemoglobin AS) is also common among black Africans and may independently cause
      endothelial damage, manifested as isolated target organ complication or
      infarction. We examined the possibility that patients with concurrent type 2
      diabetes and SCT may be predisposed to more frequent or severe diabetic macro- or
      microvascular complications than those without SCT. METHODS: Fifty-two type 2
      diabetic patients were divided into four groups, according to gender and
      hemoglobin genotype (normal: AA or SCT: AS). The groups were well matched for age
      and for clinical and demographic parameters. Diabetic complications were assessed
      in each patient and scored. Hemoglobin genotype was determined by hemoglobin-gel
      electrophoresis. Statistical comparisons were made between the groups. RESULTS:
      The composite complication score for vascular disease differed significantly
      according to gender and genotype (p<0.027 ANOVA). Male diabetics with SCT had a
      higher risk ratio (RR 1.6, p<0.02) for complications than those with normal
      hemoglobin; however, this was not the case with female diabetics. Among the male
      diabetics with SCT, there was a significantly greater proportion with proteinuria
      (p<0.02) or retinopathy (p<0.05) than among those with a normal hemoglobin
      genotype. Multiple regression analysis showed that gender and SCT were
      independent predictors of the vascular complication severity score and that
      exclusion of hemoglobin genotype weakened the predictability of the regression. A
      significantly higher proportion of male than female diabetics had at least one
      detectable complication. Systolic or diastolic blood pressure had no significant
      impact on the regressions. CONCLUSION: Male gender and SCT may adversely affect
      the expression of microvascular diabetic complications in Africans. Diabetic
      patients from populations predisposed to the sickle gene should be screened for
      the trait as part of their initial risk assessment. Large-scale studies on the
      impact of hemoglobin genotype on diabetic complications are clearly indicated.

PMID- 15450990
TI  - Sandfly fever due to Toscana virus: an emerging infection in southern France.
AB  - Infections due to Toscana virus (TOSV) have been described in the Mediterranean
      area, mainly in Italy. We describe two cases of acute TOSV infection in southern
      France, one aseptic meningitis and one influenza-like illness. To our knowledge,
      only one other case of TOSV infection has been reported in this area.

PMID- 15450991
TI  - Malignant pericardial effusion and cardiac tamponade as a late complication of
      endometrial carcinoma.
AB  - Malignant pericardial effusion, as a complication of gynecological cancer, is a
      rare occurrence. A review of the literature reveals only four cases of malignant
      pericardial effusion from endometrial carcinoma diagnosed during life. All of
      them were followed by cardiac tamponade a short time after being diagnosed and
      were associated with extensive myometrial invasion and multiple metastases. We
      describe a case of malignant pericardial effusion and cardiac tamponade due to
      recurrence of endometrial carcinoma characterized by the long period from
      diagnosis to clinical evidence of pericardial involvement. The causes of long
      term disease-free interval are discussed.

PMID- 15450992
TI  - Lung abscesses and jaundice due to prolonged Escherichia coli bacteremia
      associated with pyelonephritis: a forgotten entity.
AB  - We describe a previously healthy, middle-aged patient with prolonged bacteremia
      and Escherichia coli presenting with jaundice and lung abscesses. At
      presentation, a paucity of respiratory signs and symptoms was found, although the
      patient appeared to be very ill. The cavitary pulmonary lesions and jaundice were
      due to hematogenous spread of E. coli from a pyelonephritis. Pulmonary abscesses
      and jaundice in the setting of prolonged bacteremia due to pyelonephritis was
      frequently observed before the antibiotic era. Nowadays, it is almost a forgotten
      phenomenon.

PMID- 15450993
TI  - Vertebral osteomyelitis presenting as exudative pleural effusion.
AB  - The most common causes of exudative pleural effusion are tuberculosis,
      malignancy, and pneumonia. However, exudative pleural effusion may also reveal
      contiguous infectious processes including cholecystitis, subphrenic pus
      collection, and thoracic vertebral osteomyelitis. In the latter, the diagnosis is
      usually delayed. We report two cases of thoracic vertebral osteomyelitis
      presenting as exudative pleural effusion for which the diagnosis could be
      suspected by a careful analysis of the thoracic imaging studies performed on
      admission.

PMID- 15450994
TI  - Roxithromycin-induced torsades de pointes.
AB  - Roxithromycin is an oral macrolide antibiotic agent frequently used in the
      clinical setting. The risk of pro-arrhythmia during roxithromycin use has always
      been considered extremely remote. We describe a patient who developed
      prolongation of the QT interval and torsades de pointes under roxithromycin
      treatment.

PMID- 15450995
TI  - Pancreatic vasoactive intestinal peptide-producing tumor and hypercalcemia.

PMID- 15450996
TI  - Life-threatening anemia related to pernicious anemia cured with oral
      cyanocobalamin therapy.

PMID- 15450997
TI  - On the future of internal medicine.

PMID- 15450998
TI  - Reply to the authors.

PMID- 15450999
TI  - Microspectroscopic FT-IR mapping system as a tool to assess blend homogeneity of
      drug-excipient mixtures.
AB  - In order to prepare a controlled-release tablet by direct compression, a Fourier
      transform infrared (FT-IR) microspectroscopic mapping system was utilized to
      assess the blend homogeneity of a pharmaceutical powder blend. The model powder
      blend was a two-component mixture consisting of captopril as a model drug and
      micronized ethylcellulose (EC) as a direct-compressible model excipient, which
      was mixed in a laboratory mill. The two-component mixture was mixed in two
      different weight proportions (captopril:EC, 1:1 or 10:1). By varying the mixing
      time, different blend mixtures sampled were determined by a reflectance FT-IR
      microspectroscopic mapping system to collect successively the IR spectra from the
      actual analysis area. The results revealed that the blend homogeneity increased
      gradually with increased mixing times, but the powder began to demix or segregate
      as mixing continued beyond the time when homogeneity was reached. In addition,
      the statistical results indicated that the sample mixture proportion had an
      effect on the uniformity of the powder blend. This study demonstrates that
      microspectroscopic FT-IR mapping technique can be easily used to determine the
      blend homogeneity in a powder blend mixture.

PMID- 15451000
TI  - Evolution of the interaction of a new chemical entity, eflucimibe, with gamma
      cyclodextrin during kneading process.
AB  - The aim of this study was to enhance the low solubility of eflucimibe, a new
      chemical entity which can be used as medicine to treat dyslipidemiae, by
      complexation with gamma-cyclodextrin. The complex was prepared using kneading
      method. The interaction evolution was studied during process by comparison of the
      semi-solid and physico-chemical states of the product. The evolution of the semi
      solid state was followed by torque measurement when the evolution of physico
      chemical state was studied by differential scanning calorimetry, infrared
      spectroscopy and by determination of the drug solubilisation profile. The
      interaction, which occurs during the process, is characterised by a modification
      of the product consistency and by a disappearance of the drug endothermic peaks,
      a disappearance of a drug spectral band and a widely improvement of the drug
      solubilisation profile. Indeed, after complete interaction, the drug quantity
      solubilised in specific conditions increased about 44-fold compared to those of
      untreated drug. Moreover, the comparison of the physico-chemical and semi-solid
      states during kneading process clearly shows that when the interaction takes
      place, a solidification of the paste occurs. The results of these works suggested
      that the formation of new solid phase allows an enhancement of the solubility of
      eflucimibe.

PMID- 15451001
TI  - Photophysicals and photochemicals studies of zinc(II) phthalocyanine in long time
      circulation micelles for photodynamic therapy use.
AB  - Long time circulation systems, such as polymeric micelles, represent a growing
      area in biomedical research. These microparticles can be used in many biological
      systems to provide appropriate drug levels with a specific biodistribution. Long
      time circulation micelles (LTCM) were routinely prepared using PEG-5000-DSPE
      (polyethyleneglycol-5000-distearoil-phosphatidyl-ethanolamine) and zinc(II)
      phthalocyanine (ZnPc) as a photosensitizer and fluorescent probe. This compound
      belongs to a second generation of photoactive agents, mainly used in photodynamic
      therapy (PDT) of neoplasic tissues. Their high selectivity for tumoral target
      tissues as well as high phototoxicity based on singlet oxygen generation renders
      the utilization of these compounds feasible as an alternative therapy for cancer
      treatment. LTCM were characterized by classical spectroscopic techniques.
      Absorbance measurements indicated that the drug was s completely loaded into LTCM
      (epsilon = 2.41 x 10(5) cm(-1)). This was also verified by steady state and time
      resolved fluorescence measurements. The lifetime profiles of ZnPc decay curves
      were fitted according to biexponential function (tau1 = 3.9 ns and tau2 = 15.5
      ns) indicating different locations for ZnPc into LTCM. The time-resolved
      spectroscopy measurements for ZnPc triplet excited state lifetimes (tauT) were
      calculated from the kinetic analysis of transient decays at the absorption
      maximum (480 nm), by using laser flash photolysis technique. All the spectroscopy
      measurements performed allowed us to conclude that, ZnPc in LTCM is a promising
      drug delivery system (DDS) for PDT.

PMID- 15451002
TI  - The role of particle engineering in relation to formulation and de-agglomeration
      principle in the development of a dry powder formulation for inhalation of
      cetrorelix.
AB  - We formulated cetrorelix acetate, as an adhesive mixture for use in dry powder
      inhalation. To achieve the highest possible deposition efficiency we investigated
      both the influence of different micronization techniques and different inhalers.
      The Novolizer with an air classifier as the powder de-agglomeration principle and
      the ISF inhaler were used for in vitro deposition experiments (cascade
      impaction). Micronization by milling as the classical approach and micronization
      by spray drying and spray freeze drying as advanced particle engineering
      techniques were investigated to determine whether advanced techniques are
      necessary to obtain high fine particle fractions (FPF) for this specific drug. It
      was found that the effects obtained with a certain micronization technique
      depended on the complex interaction of the physical characteristics of the drug
      substance with the type of formulation chosen, as well as with the de
      agglomeration principle used. The combination of particle engineering by spray
      drying and the use of the air classifier technology resulted in a fine particle
      fraction of 66%, while spray freeze drying yielded extremely fragile particles
      resulting in a FPF of only 25%. The behaviour of the milled material showed
      similar trends as the spray dried material but FPF values were lower. It was
      concluded that when a drug is to be formulated as a powder for inhalation with
      high fine particle fractions, it is profitable to use advanced particle
      engineering techniques, however the applied technique should be tuned with the
      characteristics of the formulation type and process as well as with device
      development.

PMID- 15451003
TI  - Design, synthesis and in vitro evaluation of novel water-soluble prodrugs of
      buparvaquone.
AB  - Novel water-soluble phosphate prodrugs (2b-5b) of buparvaquone-oxime (1a) and
      buparvaquone-O-methyloxime (1b) were synthesized and evaluated in vitro as
      potential oral prodrugs against leishmaniasis. Buparvaquone-oxime (1a), and most
      probably also buparvaquone-O-methyloxime (1b), released the parent buparvaquone
      via a cytochrome P450-catalysed reaction. The prodrugs 2b-5b showed significantly
      higher aqueous solubilities (>4 mg/ml) than buparvaquone (< or = 0.03 microg/ml)
      over a pH range of 3.0-7.4. The prodrugs 2b, 3b and 5b rapidly released (t1/2 = 7
      min) the corresponding oximes of buparvaquone (1a and 1b), and prodrug 4b at a
      moderate rate (t1/2 = 22.5 min) in alkaline phosphatase solution in vitro.
      Prodrug 3b was the most chemically stable in the aqueous solutions over a pH
      range of 3.0-7.4 (t1/2 > 8 days). Although buparvaquone-oxime (1a) has been shown
      to undergo a cytochrome P450-catalysed oxidation in liver microsomes to the
      parent buparvaquone and behave as a novel bioreversible prodrug, its usefulness
      is limited in oral drug delivery due to its poor aqueous solubility, like
      buparvaquone itself. Further phosphorylation of an oxime form of buparvaquone
      significantly increased water solubility, and this novel approach is therefore
      useful to improve physicochemical properties of drugs containing a ketone
      functional group.

PMID- 15451004
TI  - Preparation of budesonide- and indomethacin-hydroxypropyl-beta-cyclodextrin
      (HPBCD) complexes using a single-step, organic-solvent-free supercritical fluid
      process.
AB  - The purpose of this study was to determine whether budesonide- and indomethacin
      hydroxypropyl-beta-cyclodextrin (HPBCD) complexes could be formed using a
      supercritical fluid (SCF) process. The process involved the exposure of drug
      HPBCD mixtures to supercritical carbon dioxide (SC CO2). The ability of the SCF
      process to form complexes was assessed by determining drug dissolution, drug
      crystallinity, and drug-excipient interactions. Drug dissolution was assessed
      using a HPLC assay. Crystallinity was assessed using powder X-ray diffraction
      (PXRD) and differential scanning calorimetry (DSC). Drug-excipient interactions
      were characterized using Fourier transform infrared spectroscopy (FTIR). Scanning
      electron microscopy (SEM) was used to determine any morphological changes. SC CO2
      process did not alter the dissolution rate of pure drugs but resulted in two- and
      three-fold higher dissolution rates for budesonide- and indomethacin-HPBCD
      mixtures, respectively. SCF-processed mixtures exhibited a disappearance of the
      crystalline peaks of the drugs (PXRD), a partial or complete absence of the
      melting endotherm of the drugs (DSC), and a shift in the C=O stretching of the
      carboxyl groups of the drugs (FTIR), consistent with the loss of drug
      crystallinity and formation of intermolecular bonds with HPBCD. SEM indicated no
      discernible drug crystals upon physical mixing with or without SCF processing.
      Thus, budesonide- and indomethacin-HPBCD complexes with enhanced dissolution rate
      can be formed using a single-step, organic solvent-free SC CO2 process.

PMID- 15451005
TI  - The effect of vessel material on granules produced in a high-shear mixer.
AB  - In this study the effect of different vessel wall materials on the granule size
      distributions obtained during high-shear granulation of different materials is
      investigated. The distributions obtained in glass and stainless steel vessels
      differ from those obtained in PMMA (polymethyl methacrylate) and PTFE
      (polytetrafluoroethylene) vessels. The high contact angle of PMMA forces all
      liquid immediately into the more easily wetted powder bed. In this vessel a fast
      liquid absorbing powder nucleates in the droplet controlled regime, leading to a
      narrow particle size distribution. In a vessel with a low contact angle (glass or
      stainless steel) a liquid layer can be formed on the wall surface. This liquid
      causes an inhomogeneous distribution of liquid over the powder bed; a broader
      granule size distribution is the result. With a powder that slowly absorbs
      liquid, local overwet areas can be created, resulting in large granules. This
      results in broader granule size distributions as well. In conclusion; the contact
      angle of the vessel material and the wetting rate of the powder used determine
      the granule growth process and the resulting granule size distribution.

PMID- 15451006
TI  - Substrates and inhibitors of efflux proteins interfere with the MTT assay in
      cells and may lead to underestimation of drug toxicity.
AB  - The MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay is a
      widely used method in assessment of cytotoxicity and cell viability, and also in
      anti-cancer drug studies with tumour cells. These cells often express efflux
      proteins, such as P-glycoprotein (MDR1) or multidrug resistance (MDR) protein 1
      (MRP1). MDCKII cells that overexpress these proteins (MDCKII-MDR1 or MDCKII-MRP1)
      and normal cells (MDCKII-wt) were used to investigate the effects of efflux pump
      activity on the results of MTT assay. Efflux protein activity was confirmed with
      calcein-AM efflux assay, and MTT assay was compared to another cytotoxicity test,
      the LDH release assay. Inhibition of MRP and MDR1 efflux proteins in MDCKII cell
      lines was associated paradoxically with increased reduction of MTT, implying an
      apparent increase in cell viability. This effect was seen when MK 571 (MRP1 and
      MRP2 inhibitor) or verapamil (MRP1 and MDR1 inhibitor) were used to block efflux
      protein activity. The calcein-AM efflux assay also showed that the MTT reagent
      inhibits the function of MDR1 in the MDCKII-MDR1 cell line. This study shows that
      MDR1 and possibly MRP proteins interfere with the MTT assay. Due to wide
      substrate specificity of efflux proteins and popularity of the MTT assay this
      interference is not trivial. Presence of any efflux protein substrate may
      therefore lead to underestimated results in MTT assay, thereby causing potential
      bias and erroneous conclusions in cytotoxicity studies.

PMID- 15451007
TI  - Impact of serum on clearance predictions obtained from suspensions and primary
      cultures of rat hepatocytes.
AB  - The objective of the present study was to compare two configurations of the
      hepatocyte model namely suspensions (SH) and conventional primary cultures (CPC)
      for their ability to predict the hepatic clearance in vivo in the rat and, to
      investigate the impact of serum on the prediction accuracy. The metabolic
      competences of several cytochrome P450 isoenzymes were investigated both in CPC
      and SH in the presence or absence of serum. Under the same conditions, the in
      vitro intrinsic clearance of six test compounds metabolised by a variety of phase
      I and phase II enzymes (antipyrine, RO-X, mibefradil, midazolam, naloxone and
      oxazepam) were derived from Vmax/Km scaled up to the corresponding in vivo
      hepatic metabolic clearance. CYP activities were shown to be stable in both CPC
      and SH for up to 6 h of incubation, except for the CYP 3A1 activity that
      decreased in CPC even in the presence of serum. Moreover, the clearances
      predicted from SH in the presence of serum were closer to the in vivo values than
      those obtained from CPC. SH represent a convenient model to assess the hepatic
      metabolism of xenobiotics, the presence of serum in the incubation medium
      significantly improved in several instances the quality of the predictions.

PMID- 15451008
TI  - Seizure susceptibility of neuropeptide-Y null mutant mice in amygdala kindling
      and chemical-induced seizure models.
AB  - Neuropeptide Y (NPY) administered exogenously is anticonvulsant, and, NPY null
      mutant mice are more susceptible to kainate-induced seizures. In order to better
      understand the potential role of NPY in epileptogenesis, the present studies
      investigated the development of amygdala kindling, post-kindling seizure
      thresholds, and anticonvulsant effects of carbamazepine and levetiracetam in
      129S6/SvEv NPY(+/+) and NPY(-/-) mice. In addition, susceptibility to pilocarpine
      and kainate-induced seizures was compared in NPY(+/+) and (-/-) mice. The rate
      of amygdala kindling development did not differ in the NPY(-/-) and NPY(+/+) mice
      either when kindling stimuli were presented once daily for at least 20 days, or,
      12 times daily for 2 days. However, during kindling development, the NPY(-/-)
      mice had higher seizure severity scores and longer afterdischarge durations than
      the NPY(+/+) mice. Post-kindling, the NPY(-/-) mice had markedly lower
      afterdischarge thresholds and longer afterdischarge durations than NPY (+/+)
      mice. Carbamazepine and levetiracetam increased the seizure thresholds of both
      NPY (-/-) and (+/+) mice. In addition, NPY (-/-) mice had lower thresholds for
      both kainate- and pilocarpine-induced seizures. The present results in amygdala
      kindling and chemical seizure models suggest that NPY may play a more prominent
      role in determining seizure thresholds and severity of seizures than in events
      leading to epileptogenesis. In addition, a lack of NPY does not appear to confer
      drug-resistance in that carbamazepine and levetiracetam were anticonvulsant in
      both wild type (WT) and NPY null mutant mice.

PMID- 15451009
TI  - Different effects of neuroprotectants FK-506 and cyclosporin A on susceptibility
      to pilocarpine-induced seizures in rats with brain injured at different
      developmental stages.
AB  - Susceptibility of the injured brain to epileptic seizures depends on the
      developmental stage at which the injury had been inflicted (our previous paper
      published in Epilepsy Res. 53 (2003) 216-224). The present study was designed to
      examine whether neuroprotective agents applied following the injury can decrease
      the seizure susceptibility. In order to solve this problem, the left cerebral
      hemisphere was mechanically injured in 6- and 30-day-old Wistar rats.
      Neuroprotectants FK506 or Cyclosporin A (CsA) were injected 20 min and 24h
      following the injury. On postnatal day 60, all the animals received single i.p.
      pilocarpine injections to evoke epileptic seizures. During a 6h period following
      the injection, the animals were observed continuously and pilocarpine-induced
      symptoms were recorded and rated. The animals were sacrificed 7 days after
      pilocarpine injection. In rats injured on postnatal days 6 or 30 (P6 or P30,
      respectively) and injected with FK-506 after the injury, signs of amelioration in
      the course of epilepsy were observed. Generally, proportions of rats suffering
      from heavy seizures were lower and/or their survival periods were longer.
      Following treatment with CsA, proportions of rats displaying heavy seizures were
      greater. It was accompanied by extremely high mortality (in rats injured on P6)
      or a longer duration of seizures (in rats injured on P30). The results appear to
      point to age-dependent differences between the mechanisms of action of the two
      neuroprotectants.

PMID- 15451010
TI  - Impulse response function based on multivariate AR model can differentiate focal
      hemisphere in temporal lobe epilepsy.
AB  - The purpose of this study is to propose and investigate a new approach for
      discriminating between focal and non-focal hemispheres in intractable temporal
      lobe epilepsy, based on applying multivariate time series analysis to the
      discharge-free background brain activity observed in nocturnal electrocorticogram
      (ECoG) time series. Five unilateral focal patients and one bilateral focal
      patient were studied. In order to detect the location of epileptic foci, linear
      multivariate autoregressive (MAR) models were fitted to the ECoG data; as a new
      approach for the purpose of summarizing these models in a single relevant
      parameter, the behavior of the corresponding impulse response functions was
      studied and described by an attenuation coefficient. In the majority of
      unilateral focal patients, the averaged attenuation coefficient was found to be
      almost always significantly larger in the focal hemisphere, as compared to the
      non-focal hemisphere. Also the amplitude of the fluctuations of the attenuation
      coefficient was significantly larger in the focal hemisphere. Moreover, in one
      patient showing a typical regular sleep cycle, the attenuation coefficient in the
      focal hemisphere tended to be larger during REM sleep and smaller during Non-REM
      sleep. In the bilateral focal patient, no statistically significant distinction
      between the hemispheres was found. This study provides encouraging results for
      new investigations of brain dynamics by multivariate parametric modeling. It
      opens up the possibility of relating diseases like epilepsy to the properties of
      inconspicuous background brain dynamics, without the need to record and analyze
      epileptic seizures or other evidently pathological waveforms.

PMID- 15451011
TI  - Pre-ictal synchronicity in limbic networks of mesial temporal lobe epilepsy.
AB  - PURPOSE: We recorded with intracerebral electrodes the onset of limbic seizures
      in patients with mesial temporal lobe epilepsy (MTLE) to identify the dynamic
      interactions between the hippocampus (HIP), amygdala (AMY) and entorhinal cortex
      (EC). METHODS: Interactions were quantified by analyzing the interdependencies
      between stereo-electroencephalographic (SEEG) signals using a nonlinear cross
      correlation method. Seizures from 12 patients were analyzed by identifying three
      periods of interest: (i) the rapid discharge that occurs at seizure onset
      ("during rapid discharge", DRD period); (ii) the time interval that precedes this
      rapid discharge ("before rapid discharge", BRD period); and the time that follows
      the rapid discharge ("after rapid discharge", ARD period). The transition from
      interictal to ictal discharge was classified into: (i) "type 1 transition" in
      which the emergence of pre-ictal spiking was followed by a rapid discharge; and
      (ii) "type 2 transition" that was associated with rapid discharge onset without
      prior spiking. RESULTS: In both types of transition the BRD period was
      characterized by significant cross-correlation values indicating strong
      interactions among mesial temporal structures as compared to those seen during
      background activity. Interactions between HIP and EC were predominant in 10 of 12
      patients (83%). Interactions between EC and AMY were observed in 6 of 12 cases
      (50%) and between AMY and HIP in 7 of 12 cases (58%). Analysis of coupling
      directionality indicated that most of the couplings were driven either by HIP
      (six patients) or by the EC (four patients). The DRD period was characterized by
      a significant decrease of cross-correlation values. In addition, type 1
      transition was characterized by interactions that uniformly involved the three
      structures, while type 2 transition was associated with interactions between EC
      and HIP. Finally, analysis of coupling direction demonstrated that the HIP was
      always the leader in type 1 transition whereas in type 2 the EC was most often
      the leading structure. CONCLUSIONS: This study demonstrates that pre-ictal
      synchronization between mesial structures is the initial event for seizures
      starting in the mesial temporal region.

PMID- 15451012
TI  - Quantitative evaluation of central-type benzodiazepine receptors with [(125)I]
      Iomazenil in experimental epileptogenesis. I. The rat kainate model of temporal
      lobe epilepsy.
AB  - This study aimed at quantitatively evaluating hippocampal central-type
      benzodiazepine receptors (BZRs) in the kainate model of temporal lobe epilepsy
      (TLE) by in vitro autoradiography (ARG) using [(125)I] Iomazenil (IMZ) specific
      ligand for central-type BZRs. Kainate (1 microg/0.5 microl) was injected into the
      left amygdala to induce limbic status epilepticus. One, three, or six months
      after injection, in vitro ARG with [(125)I] IMZ and cell counts were performed in
      the hippocampal CA1-4 regions and dentate gyrus ipsilateral to the kainate
      injection site, and were compared with the vehicle-injected control group. In all
      kainate-treated rats, clear pyramidal neuron loss was observed in left
      hippocampal areas CA1-4. Compared with the control group, progressive reduction
      of [(125)I] IMZ binding was also observed. This resulted in a marked binding
      decrease paralleling pyramidal neuron loss in hippocampal areas CA1 (down to 83%
      of control), CA2 (76%), CA3 (75%), and CA4 (90%) at 6 months after kainate
      administration. Conversely, [(125)I] IMZ binding significantly increased in the
      dentate gyrus (up to 106% of control) at 1 month, but returned to nearly normal
      at 3-6 months. These results suggest that central-type BZR neuroimaging is useful
      in detecting hippocampal sclerosis in the mesial TLE, though central BZR
      alterations differ depending on hippocampal subfields and post-seizure time
      courses.

PMID- 15451013
TI  - Quantitative evaluation of central-type benzodiazepine receptors with
      [(125)I]Iomazenil in experimental epileptogenesis: II. The rat cortical dysplasia
      model.
AB  - [(123)I]Iomazenil (IMZ) is a specific ligand for central-type benzodiazepine
      receptors (BZRs) and is available for single photon emission computed tomography
      (SPECT) to detect epileptogenic foci. We have recently demonstrated time
      dependent alterations of [(125)I]IMZ binding in the rat kainate model of temporal
      lobe epilepsy. Quantitative evaluation of central-type benzodiazepine receptors
      with [(125)I]Iomazenil in experimental epileptogenesis. I. The rat kainate model
      of temporal lobe epilepsy. In the present study, we investigated regional changes
      in central-type BZRs in the cortical dysplasia (CD) model of epilepsy in rats.
      Pregnant rats were irradiated at day 17 of gestation with 1.2 Gy to produce CD in
      their pups, and in vitro autoradiography with [(125)I]IMZ was performed at 8
      weeks after birth. Intact rats at the same age were used as controls. [(125)I]IMZ
      binding was significantly decreased in various cortical regions of the in utero
      irradiated rats, including the bilateral frontal cortex (down to 92-93% of
      control), cingulate cortex (91-92%), hippocampal areas CA1 (95%), CA2 (94-95%)
      and CA4 (95-96%), and caudate/putamen (90-94%). In addition, amygdala-kindling
      was significantly facilitated in the CD model, especially during the late phase
      of kindling, suggesting seizure susceptibility of this model. These results may
      replicate the clinical usefulness of central-type BZRs neuroimaging for detection
      of human epileptogenic CD and indicate dysfunction of GABA-A/BZR-mediated
      inhibition responsible for the seizure susceptibility.

PMID- 15451014
TI  - Atipamezole, an alpha(2)-adrenoceptor antagonist, has disease modifying effects
      on epileptogenesis in rats.
AB  - Stimulation of alpha(2)-adrenoceptors delays the development of kindling, a model
      of epileptogenesis in humans. Blocking alpha(2)-adrenoceptors is proconvulsant,
      but has beneficial effects on somatomotor recovery after experimental stroke. We
      investigated whether atipamezole, a selective alpha(2)-adrenoceptor antagonist,
      affects the recovery process from status epilepticus (SE)-induced brain damage,
      which affects the risk of epileptogenesis. Vehicle or atipamezole (100
      microg/kg/h) treatment was started 1 week after the induction of SE and continued
      for 9 weeks using Alzet minipumps (n = 70). Development and severity of epilepsy,
      spatial and emotional learning, and histologic analysis were used as outcome
      measures. There were no differences in the percentage of animals with epilepsy in
      the different treatment groups. In the atipamezole group, however, daily seizure
      frequency was lower (P < 0.01), a higher percentage of epileptic animals had mild
      epilepsy (<1 seizure/day; P < 0.01), and seizure frequency did not increase over
      time compared with the vehicle group. The atipamezole group had milder hilar cell
      damage (P < 0.05) and less intense mossy fiber sprouting (P < 0.05). Behavioral
      impairments were similar between groups. Our data indicate that chronic treatment
      with atipamezole does not prevent epileptogenesis. There is, however, a disease
      modifying effect; that is, the epilepsy that develops is milder and non
      progressive. These data warrant further studies.

PMID- 15451015
TI  - Regional expression of the radial glial marker vimentin at different stages of
      the kindling process.
AB  - The classical view of the function of radial glia in brain development is a
      supporting function guiding radial neural migration. However, recent evidence
      indicates that they may play key roles in neurogenesis and gliogenesis, as
      ubiquitous precursors that generate neurons and glia. Although we previously
      reported the emergence of radial glia after spinal cord injury in adult rats,
      their precise function in this process is still unknown. In the present study, we
      examined emergence of radial glia in rat brain during progression of kindling, by
      performing immunohistochemical staining for vimentin which is a specific marker
      of radial glia. Vimentin immunoreactivity was found to be highest at clonus 3 and
      then decreased at clonus 5 in the hippocampal formation, regions around the third
      ventricle, caudate putamen and lateral habenular nucleus. Contrast, vimentin
      immunoreactivity consistently increased with progression of kindling in the
      cingulum and parietal cortex. These findings indicate dynamic changes in vimentin
      expression dependent on the kindling stage of seizure-prone state, and suggest
      that these changes play roles in formation of new circuits following kindling.

PMID- 15451016
TI  - The unilateral cobalt wire model of neocortical epilepsy: a method of producing
      subacute focal seizures in rodents.
AB  - In the course of experiments on focal epilepsy in rats, we have recognized that
      there are no adequate models of subacute focal epilepsy in rodents. We have,
      therefore, reevaluated a previously described rat model that reliably generates
      subacute seizures over 2-3 weeks. After implantation of a short length of cobalt
      wire into the left motor cortex, the animals are monitored by standard EEG over
      the next 3 weeks. They develop three seizure types: 1. Simple partial seizures
      with contralateral clonic jerks, lasting 17.9 +/- 46.4 min; these seizures were
      characterized by repetitive single spikes; 2. Secondarily generalized seizures,
      lasting 34.5 +/- 19.0 s; and 3. Complex partial seizures with a paroxysmal EEG,
      lasting 39.6 +/- 55.5 s. Post mortem brains were imaged using standard magnetic
      resonance techniques, after removal of the ferromagnetic cobalt wire. There was a
      localized loss of the MR signal that differed by pulse sequence, indicating
      spread of the ferromagnetic cobalt into the brain tissue. The image disruption
      caused by the cobalt was quite abrupt, indicating a sharp cobalt concentration
      gradient. However, we saw no evidence of widespread cerebral injury. The
      unilateral cobalt wire model generates less frequent, but more persistent
      seizures than seen in most acute, focal models. The ferromagnetic signal present,
      even after wire removal, indicates that metallic cobalt leaches into the cortex
      and may be responsible for generating the seizures. This model should be useful
      for testing new therapies for neocortical epilepsy.

PMID- 15451017
TI  - Contribution of GABA(B) receptor-mediated inhibition to the expression and
      termination of group I mGluR-induced ictaform bursts.
AB  - In guinea pig hippocampal slices, the GABA(B) receptor antagonist CGP 35348
      increased the length of picrotoxin-induced interictal bursts by only 22%, yet it
      increased the length of group I mGluR-induced ictaform bursts by 85%. These data
      suggest that (1) suppression of GABAergic inhibition is insufficient to account
      for group I mGluR agonist-induced ictaform bursts, and (2) although GABA(B) plays
      a minor role in terminating interictal bursts, it is a major contributor to the
      termination of mGluR-induced ictaform bursts.

PMID- 15451018
TI  - Characteristics and phenomenology of epileptic partial seizures in dogs:
      similarities with human seizure semiology.
AB  - Dogs with spontaneous occurring epilepsy with partial seizures express
      symptomatology resembling what is found in humans with partial epileptic
      seizures. Questionnaires on clinical signs from 70 dogs, with a confirmed
      diagnosis of epilepsy with partial seizures with or without secondary
      generalization, were reviewed in order to characterize and classify clinical
      signs of partial seizure activity in dogs and compare them to partial seizure
      phenomenology in humans. Signs of partial seizure activity were distributed into
      three categories: motor signs, autonomic signs and paroxysms of behavioral signs.
      Motor signs were described in 48 dogs (69%), autonomic signs in 16 dogs (23%) and
      paroxysms of behavioral signs in 56 dogs (80%). The majority of dogs expressed
      signs from more than one group. Sixty-one dogs (87%) had partial seizures with
      secondary generalization. Nine dogs (13%) had partial seizures without secondary
      generalization. The study shows a remarkable resemblance between the seizure
      phenomenology expressed in humans and canines with partial epileptic seizures.

PMID- 15451019
TI  - Signalling via the hypoxia-inducible factor-1alpha requires multiple
      posttranslational modifications.
AB  - Cellular hypoxia, a local decrease in the oxygen concentration below normal (21%)
      atmospheric concentrations, occurs in both physiological and pathological
      situations. The transcriptional complex Hypoxia-Inducible Factor-1 (HIF-1) is the
      key player in the signalling pathway that controls the hypoxic response of
      mammalian cells. Tight regulation of this response involves posttranslational
      modification of the alpha subunit of HIF-1. Hydroxylation, ubiquitination,
      acetylation, S-nitrosation and phosphorylation have been shown to determine its
      half-life and/or transcriptional activity. The precise spatio-temporal occurrence
      of these multiple modifications is still not fully understood but is dependent on
      the microenvironment and determines the driving force of variable cellular
      responses.

PMID- 15451020
TI  - Subversion of immunological signalling by a filarial nematode phosphorylcholine
      containing secreted product.
AB  - Modulation of immune responses is an important strategy employed by pathogens to
      enable their survival in host organisms. Secreted immunomodulatory molecules are
      key weapons in the pathogen's battle with the host immune system. In this review,
      we will discuss the immunomodulatory effects of the phosphorylcholine-containing
      filarial nematode glycoprotein, ES-62, on the host immune system and summarise
      the results of our studies to identify the intracellular signalling pathways
      targeted by ES-62 to achieve these effects.

PMID- 15451021
TI  - Mutations in the carboxy-terminus of the third intracellular loop of the human
      recombinant VPAC1 receptor impair VIP-stimulated [Ca2+]i increase but not
      adenylate cyclase stimulation.
AB  - The vasoactive intestinal polypeptide (VIP) VPAC1 receptor is preferentially
      coupled to Galphas protein that stimulates adenylate cyclase activity and also to
      Galphaq and Galphai proteins that stimulate the inositol phosphate/calcium
      pathway. Previous studies indicated the importance of the third intracellular
      loop of the receptor for G protein coupling. By site-directed mutation of the
      human recombinant receptor expressed in Chinese hamster ovary cells, we
      identified two domains in this loop that contain clusters of basic residues
      conserved in most of the G-protein-coupled seven transmembrane domains receptors.
      We found that mutations in the proximal domain (K322) reduced the capability of
      VIP to increase adenylate cyclase activity without any change in the calcium
      response, whereas mutations in the distal part of the loop (R338, L339, R341)
      markedly reduced the calcium increase and Galphai coupling but only weakly the
      adenylate cyclase activity. Thus, the interaction of different G proteins with
      the VPAC1 receptor involves different receptor sub-domains.

PMID- 15451022
TI  - Cannabinoids down-regulate PI3K/Akt and Erk signalling pathways and activate
      proapoptotic function of Bad protein.
AB  - Cannabinoids were shown to induce apoptosis of glioma cells in vitro and tumor
      regression in vivo, but mechanisms of their antiproliferative action remain
      elusive. In the present studies, C6 cells were exposed to a synthetic
      cannabinoid, WIN 55,212-2, which produced down-regulation of the Akt and Erk
      signalling pathways prior to appearance of any sign of apoptosis. We hypothesized
      that cannabinoid-induced cell death may be mediated by a Bcl-2 family member-
      Bad, whose function is hampered by these kinases due to control of its
      phosphorylation state. Using Western blot analysis, we found that levels of
      phosphorylated Bad, but not total Bad protein, decreased under exposure to WIN
      55,212-2. WIN 55,212-2 treatment further resulted in mitochondrial depolarization
      and activation of caspase cascade. Thus, we suggest that the increase of
      proapoptotic Bad activity is an important link between the inhibition of survival
      pathways and an onset of execution phase of cannabinoid-induced glioma cell
      death.

PMID- 15451023
TI  - Regulation of aryl hydrocarbon receptor signal transduction by protein tyrosine
      kinases.
AB  - The involvement of protein tyrosine kinases (PTKs) in aryl hydrocarbon receptor
      (AhR)-mediated signalling by omeprazole and 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD) was investigated in hepatoma cells. Both omeprazole- and TCDD-dependent
      AhR signalling was attenuated by inhibition of c-src kinase, either by using
      pyrazolopyrimidine 4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4 ]pyrimidine
      (PP1) and 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2)
      inhibitors or by expression of dominant-negative c-src. These results indicate
      that the overall AhR function is modulated by c-src kinase activity. In contrast,
      a selective inhibition of omeprazole-mediated AhR signalling was revealed by
      tyrosine kinase inhibitors, tyrphostins AG17 and AG879. Furthermore, omeprazole
      dependent AhR activation was abolished by mutation of Tyr320 to Phe, suggesting
      that this residue is a putative phosphorylation site. TCDD-dependent AhR
      signalling was neither affected by tyrphostins nor by this mutation. Our results
      are consistent with activation of the AhR by omeprazole in a ligand-independent
      manner, via a signal transduction pathway that involves protein tyrosine kinases,
      and are different from the mechanism exerted by high-affinity ligands.

PMID- 15451024
TI  - Role of specific protein kinase C isoforms in modulation of beta1- and beta2
      adrenergic receptors.
AB  - The function of beta-adrenergic receptor (betaAR) is modulated by the activity
      status of alpha1-adrenergic receptors (alpha1ARs) via molecular crosstalk, and
      this becomes evident when measuring cardiac contractile responses to adrenergic
      stimulation. The molecular mechanism underlying this crosstalk is unknown. We
      have previously demonstrated that overexpression of alpha1B-adrenergic receptor
      (alpha1BAR) in transgenic mice leads to a marked desensitization of betaAR
      mediated adenylyl cyclase stimulation which is correlated with increased levels
      of activated protein kinase C (PKC) beta, delta and [J. Mol. Cell. Cardiol. 30
      (1998) 1827]. Therefore, we wished to determine which PKC isoforms play a role in
      heterologous betaAR desensitization and also which isoforms of the betaAR were
      the molecular target(s) for PKC. In experiments using constitutively activated
      PKC expression constructs transfected into HEK 293 cells also expressing the
      beta2AR, constitutively active (CA)-PKC overexpression was first confirmed by
      immunoblots using specific anti-PKC antibodies. We then demonstrated that the
      different PKC subtypes lead to a decreased maximal cAMP accumulation following
      isoproterenol stimulation with a rank order of PKCalpha > or =
      PKCzeta>PKC>PKCbetaII. However, a much more dramatic desensitization of adenylyl
      cyclase stimulation was observed in cells co-transfected with different PKC
      isoforms and beta1AR. Further, the modulation of beta1AR by PKC isoforms had a
      different rank order than for the beta2AR: PKCbetaII>PKCalpha>PKC>PKCzeta. PKC
      mediated desensitization was reduced by mutating consensus cAMP-dependent protein
      kinase (PKA)/PKC sites in the third intracellular loop and/or the carboxy
      terminal tail of either receptor. Our results demonstrate therefore that the
      beta1AR is the most likely molecular target for PKC-mediated heterologous
      desensitization in the mammalian heart and that modulation of adrenergic receptor
      activity in any given cell type will depend on the complement of PKC isoforms
      present.

PMID- 15451025
TI  - Novel insulin-elicited phosphoproteins in adipocytes.
AB  - Akt is a key insulin-activated protein kinase. We searched for Akt substrates in
      3T3-L1 adipocytes by means of immunoprecipitation with an Akt phosphomotif
      specific antibody (PAS antibody). Four insulin-elicited phosphoproteins were
      isolated and identified by mass spectrometry. The identity of each protein was
      established by isolating the protein from lysates of untreated and insulin
      treated adipocytes with an antibody specific for the protein and showing that the
      PAS antibody reacted only with the protein in the immunoprecipitate from insulin
      treated cells. These proteins have sizes of 47, 75, 105, and 250 kDa on SDS PAGE,
      and have been designated pp47, 75, 105, and 250. The effect of inhibitors on the
      phosphorylation of the proteins, the identified sites of phosphorylation, and in
      vitro phosphorylation by recombinant Akt further indicated that pp47, 105, and
      250 are likely to be Akt substrates, whereas pp75 may not be. pp47 and 105 are
      novel proteins with no known or predicted function. pp75 was previously found as
      a protein that associated with the colony-stimulating factor receptor, designated
      as Fms-interacting protein. pp250 is a novel protein with a predicted GTPase
      activating protein (GAP) domain for Rheb and/or Rap at its carboxy terminus. The
      subcellular and tissue distributions of the four proteins were determined.

PMID- 15451026
TI  - Signalling pathways in the induction of proteasome expression by proteolysis
      inducing factor in murine myotubes.
AB  - The mechanism by which the tumour product proteolysis-inducing factor (PIF)
      induced increased expression of the ubiquitin-proteasome proteolytic pathway was
      studied in C2C12 murine myotubes. PIF directly increased total protein breakdown
      at concentrations between 4 and 16 nM, and the effect was attenuated by
      eicosapentaenoic acid (EPA) and the 12/15-lipoxygenase inhibitor 2,3,5-trimethyl
      6-(3-pyridylmethyl)1,4-benzoquinone (CV-6504). PIF induced an increased
      expression of mRNA for proteasome alpha (C2) and beta (C5) subunits over the same
      concentration range as that inducing protein degradation and with a maximal
      effect 4 h after PIF addition. The effect was attenuated by both EPA and CV-6504,
      suggesting the role of a lipoxygenase metabolite in the increased gene
      transcription. 15(S)-Hydroxyeicosatetraenoic acid [15(S)-HETE], an intermediate
      in intracellular signalling by PIF was shown to activate protein kinase
      Calpha(PKC) over the same concentration range as that inducing proteasome
      expression and both effects were attenuated by calphostin C, a highly specific
      inhibitor of PKC. 15(S)-HETE induced phosphorylation and degradation of
      IkappaBalpha at the same concentrations as those inducing 20S proteasome
      expression, and this effect was attenuated by calphostin C, suggesting the
      mediation of PKC. These results suggest potential control points in proteasome
      activation that could be useful for therapeutic intervention.

PMID- 15451027
TI  - Lysophosphatidic acid increases phosphatidic acid formation, phospholipase D
      activity and degranulation by human neutrophils.
AB  - I-oleoyl-sn-glycero-3-phosphate, a lysophosphatidic acid (LPA), in serum is a
      biologically active lipid and has multiple functions depending on the cell types.
      Several studies have shown that LPA stimulates phospholipase D (PLD) activity in
      fibroblasts and prostate cancer cells in culture. PLD plays a central role in
      regulating neutrophil functions. One of the functions of the lipid product,
      phosphatidic acid (PA), of PLD action in neutrophils is to promote degranulation.
      In the present study, we examined the effect of LPA on PLD activity and
      degranulation by human neutrophils. The results show that exogenous LPA increased
      PA formation, PLD activity and degranulation by human neutrophils in a time and
      concentration dependent manner. These findings suggest that LPA released from
      activated platelets during blood clotting may participate in bacterial killing
      and wound healing process. On the other hand, augmented LPA production might be
      involved in inflammation, causing damage of the host tissues.

PMID- 15451028
TI  - Differential change of Ins-P3-Ca2+ signaling during culture of rat hepatocytes.
AB  - Decrease of alpha-adrenergic responses during primary culture of rat hepatocytes
      was studied. Activation of glycogen phosphorylase by phenylephrine was decreased
      in the early stage of the culture (within 6 h), however, Ins-P3 production was
      almost intact until 12 h of the culture and then declined. alpha-Adrenoceptor
      mediated Ca2+-mobilization and Ins-P3-induced Ca2+ release from microsomal
      fractions were decreased in the early stage of the culture, similar to the above
      change of phosphorylase activation. We found that decrease of Ins-P3-binding
      sites in the early stage of the culture was the cause of differential change of
      Ins-P3-Ca2+ signaling during the culture of hepatocytes. Similar changes
      described above were also observed in vasopressin-induced responses. However, the
      changes of Ins-P3-Ca2+ signaling did not occur in a high-cell density culture of
      rat hepatocytes. In conclusion, the loss of phenylephrine- and vasopressin
      induced responses in cultured liver cells appear to be due to change of Ins-P3
      binding sites as well as decreased Ins-P3 production due to reduction of receptor
      numbers.

PMID- 15451029
TI  - Bombesin and angiotensin II rapidly stimulate Src phosphorylation at Tyr-418 in
      fibroblasts and intestinal epithelial cells through a PP2-insensitive pathway.
AB  - Src is activated in response to a variety of growth factors and hormones that
      bind G protein-coupled receptors (GPCRs), and its activity is regulated by
      phosphorylation at key sites, including the autophosphorylation site Tyr-418 and
      the inhibitory site Tyr-529. To better understand the mechanisms controlling Src
      activation, we examined Src phosphorylation in Swiss 3T3 fibroblasts stimulated
      with bombesin and in IEC-18 intestinal epithelial cells stimulated with
      angiotensin II (Ang II). Phosphorylation at Src Tyr-418, the activation loop
      site, was rapidly and markedly increased after GPCR agonist addition in both cell
      types. However, treatment of intact cells with the selective Src family kinase
      inhibitor PP2, at concentrations which abolished Src-mediated phosphorylation of
      focal adhesion kinase (FAK) at Tyr-577, unexpectedly led to increased
      phosphorylation at Src Tyr-418 and diminished phosphorylation at Tyr-529. In
      Swiss 3T3 cells, PP2 enhanced Tyr-418 phosphorylation after 1 min of bombesin
      stimulation, while in IEC-18 cells, PP2 increased Ang II-stimulated Tyr-418
      phosphorylation at all times tested. These results imply that a distinct, non-Src
      family kinase may be responsible for phosphorylating Src at Tyr-418 in intact
      fibroblasts and epithelial cells stimulated by GPCR agonists.

PMID- 15451030
TI  - Lyn contributes to regulation of multiple Kit-dependent signaling pathways in
      murine bone marrow mast cells.
AB  - SCF induces autophosphorylation of Kit and activates a variety of signaling
      components including Jnks, Erks, PI 3 Kinase, the JAK-Stat pathway and members of
      the Src family. Previously we showed that Lyn is activated at multiple points
      during SCF-induced cell cycle progression and contributes to SCF-mediated growth,
      chemotaxis and internalization of Kit. However, the Kit-dependent biochemical
      events that require Lyn are unknown. In this study, we used Lyn-deficient bone
      marrow mast cells (BMMC) to examine the contribution of this Src family member to
      tyrosine phosphorylation of Kit and SCF-induced activation of Jnks, Akt, Stat3
      and Erks. Although surface expression of Kit was increased in Lyn-deficient BMMC,
      SCF-induced phosphorylation and growth was reduced compared to wild-type BMMC.
      Downstream of Kit, SCF-induced activation of Jnks was markedly reduced in Lyn
      deficient BMMC. Further, Lyn was required for SCF-induced tyrosine
      phosphorylation of Stat3. Interestingly, Kit was constitutively associated with
      PI 3 Kinase in Lyn-deficient BMMC and this correlated with constitutive
      phosphorylation of Akt. This was in marked contrast to wild-type BMMC, where both
      these events were induced by SCF. These data indicate that in BMMC, Lyn
      contributes to SCF-induced phosphorylation of Kit, as well as phosphorylation of
      Jnks and Stat3. In contrast, Lyn may negatively regulate the PI 3 Kinase/Akt
      pathway. The opposing effects of Lyn on these signaling pathways may explain the
      pleiotropic effects ascribed to this Src family member in the literature.

PMID- 15451031
TI  - Activation of Raf1 and the ERK pathway in response to l-ascorbic acid in acute
      myeloid leukemia cells.
AB  - L-ascorbic acid (LAA) shows cytotoxicity and induces apoptosis of malignant cells
      in vitro, but the mechanisms by which such effects occur have not been
      elucidated. In the present study, we provide evidence that the ERK MAP kinase
      pathway is activated in response to LAA (< 1 mM) in acute myeloid leukemia cell
      lines. LAA treatment of cells induces a dose-dependent phosphorylation of
      extracellular signal-regulated kinases (ERK) and results in activation of its
      catalytic domain. Our data also demonstrate that the small G protein Raf1 and
      MAPK-activated protein kinase 2 are activated by LAA as an upstream and a
      downstream regulator of ERK, respectively. Although the ERK pathway has been
      known to activate cell proliferation, pharmacologic inhibition of ERK reduces LAA
      dependent apoptosis and growth inhibitory response of acute myeloid leukemia cell
      lines, suggesting that this signaling cascade positively regulates induction of
      apoptotic response by LAA.

PMID- 15451032
TI  - Up-regulation of mouse mast cell protease-6 gene by transforming growth factor
      beta and activin in mast cell progenitors.
AB  - Previous studies have revealed that members of the transforming growth factor
      beta (TGF-beta) including TGF-beta1 and activin A modulate the function of mast
      cells. Here we show the up-regulation of mouse mast cell protease-6 (mMCP-6),
      which is expressed in differentiated mast cells, by TGF-beta1 and activin A in
      bone marrow-derived cultured mast cell progenitors (BMCMCs). Quantitative real
      time RT-PCR analyses revealed that the mRNA level of mMCP-6 was slightly but
      reproducibly increased by treatment with TGF-beta1 or activin A, which was
      regulated at the transcription level. Reporter assays showed that Smad3, a signal
      mediator of the TGF-beta/activin pathway, was responsible for the transcription.
      The TGF-beta response element is located at -153 bp relative to the transcription
      initiation site, CAGA. Microphthalmia-associated transcription factor (MITF), a
      tissue-specific transcription factor predominantly expressed in mast cells,
      melanocytes, the heart and skeletal muscle, also stimulated the transcription of
      mMCP-6. The region at -166 bp, GACCTG, was responsible for MITF-induced
      transcription. Mutations of the CAGA motif and the MITF responsive site indicated
      that the MITF site of mMCP-6 promoter is indispensable for the transcriptional
      activation by a constitutively active TGF-beta receptor (ALK5-TD), whereas the
      CAGA motif is dispensable for transcription by MITF. Transcriptional activation
      of mMCP-6 by the TGF-beta pathway was differently interacted with that by MITF
      isoform; ALK5-TD further enhanced MITF-E-induced transcription, whereas MITF-M
      induced transcription abolished responsiveness to ALK5-TD. The positive
      regulation of mMCP-6 by the TGF-beta/activin pathway and the differential
      regulation by the MITF isoform suggest a rigorous regulation of mast cell
      function as effector cells of immune response.

PMID- 15451033
TI  - The use of zebrafish (Danio rerio) as a model system in neurobehavioral
      toxicology.

PMID- 15451034
TI  - Zebrafish as a neurotoxicological model.
AB  - At a time when common regulatory pathways are being identified in several
      different species and genomics is beginning to allow comparisons of genes, how
      they are arranged on chromosomes and how they are regulated, zebrafish has
      emerged as a valuable and complementary vertebrate model. Some of the
      characteristics that prove of value are described and illustrated. Fluorescent
      transgenic lines of zebrafish embryos are presented for time-line studies with
      neurotoxicants. While genetic knockout technology has yet to be developed for the
      model, the anti-sense, morpholino approach allows for knockdown of expression of
      genes for the 3 day, embryonic period. This can provide for phenocopies of mutant
      genes for those genes essential to embryonic development or it can provide for a
      limited inhibition of gene expression that allows subsequent development of the
      fish. With the zebrafish genomic sequencing effort, microarray technology is now
      developing for the model system. These resources and technologies allow one to
      challenge the system with toxicants, and to view the immediate effects of the
      toxicants with transgenic embryos that fluoresce in part or all of the nervous
      system. Behavioral and learning protocols have been developed for the organism so
      that early exposures can be assayed for effects upon adult fish. Microarray
      technology should allow for one to identify specific genes and pathways affected
      by a neurotoxicant. In the future, these approaches should provide a working
      protocol for exploring molecular mechanisms of neurotoxicants. This type of
      complementary approach should then allow for more efficient examination and
      testing of mechanisms in mammalian models.

PMID- 15451035
TI  - Developmental chlorpyrifos effects on hatchling zebrafish swimming behavior.
AB  - Chlorpyrifos (CPF), a widely used organophosphate insecticide and potent
      acetylcholinesterase inhibitor, interferes with neurobehavioral development. Rat
      models have been key in demonstrating that developmental CPF exposure causes
      learning deficits and locomotor activity alterations, which persist into
      adulthood. Complementary nonmammalian models can be useful in determining the
      neurodevelopmental mechanisms underlying these persisting behavioral effects.
      Zebrafish (Danio rerio) with their clear chorion and extensive developmental
      information base provide an excellent model for assessment of molecular processes
      of toxicant-impacted neurodevelopment. We have developed methods for assessing
      spatial discrimination learning in adult zebrafish and have documented persisting
      effects of developmental CPF exposure on swimming activity and learning after low
      and high doses of CPF (10 and 100 ng/ml) administered to zebrafish embryos on
      Days 1-5 postfertilization (pf). In the current study, we developed methods for
      behavioral assessment of CPF exposure on swimming activity in newly hatched
      zebrafish. An equal area segmented annular grid (concentric circles divided into
      quadrants through the diameter) was made in a 16-mm diameter cylinder. The test
      area was placed on a heating device secured to an Olympus SZH10 dissecting scope
      stage. Zebrafish embryos were exposed to 10 ng/ml CPF, 100 ng/ml CPF, or vehicle
      control (25 microl/ml DMSO) (n=8-10/treatment group). Each treatment group was
      kept in a total volume of 25 ml of egg water (60 mg/ml Instant Ocean) including
      DMSO with or without CPF mixed to above dilutions in an incubator set at 28.5
      degrees C. CPF dilutions or vehicle were changed daily with exposure ending on
      Day 5 pf. Testing of larval zebrafish was performed on Days 6 and 9 pf. The fish
      were placed in the test cylinder with 1.5 ml of egg H(2)O (28.5 degrees C). After
      a 2-min acclimation period, the swimming activity of the fish was measured for a
      3-min testing session. The 100 ng/ml CPF dose caused significant slowing of
      swimming activity on Days 6 and 9 pf and had persisting effects of impairing
      spatial discrimination and decreasing response latency in adulthood.
      Developmental exposure to 10 ng/ml of CPF did not cause a significant change in
      locomotor activity during the period soon after hatching. CPF exposure during
      early development caused clear behavioral impairments detectable during the
      posthatching period. In a previous study, we found that early developmental CPF
      exposure caused behavioral alterations in zebrafish, which lasted throughout
      adulthood. The molecular mechanisms by which early developmental CPF exposure
      produces these behavioral impairments expressed in adulthood can now be studied
      in the zebrafish model.

PMID- 15451036
TI  - Effects of dizocilpine (MK-801) on circling behavior, swimming activity, and
      place preference in zebrafish (Danio rerio).
AB  - Glutamate transmission plays an important role in many behavioral systems,
      including motor activity, learning, and memory. The noncompetitive NMDA receptor
      antagonist (+)MK-801 has been shown to increase motor activity and impair
      learning and memory in a variety of tasks in rats, mice, and other species. In an
      attempt to characterize the effects of MK-801 on motor activity and cognitive
      performance in an emerging neurobehavioral model, the zebrafish (Danio rerio), we
      examined the effects of MK-801 on circling behavior, swimming activity, and
      latency to enter, as well as preference for, an enriched chamber (EC). In
      Experiment 1, the effects of a 37-min acute exposure to (+)MK-801 (0, 2.0, and
      20.0 microM) on circling behavior were measured in a round observation chamber.
      (+)MK-801 was observed to increase circling behavior in a dose-dependent manner.
      In the second experiment, fish were treated with 0, 2, 20, or 200 microM (+)MK
      801 for 1 h, and swimming activity was measured in a rectangular observation
      chamber for 60 min following dosing. The lowest dose of (+)MK-801 decreased
      swimming activity. In the third experiment, fish were treated with either 0 or 20
      microM (+)MK-801 for 1 h each day over four consecutive days. The fish were
      tested in a modified T-maze to assess both latency to enter, and preference for,
      an EC 24, 27, and 48 h after the last treatment. The results showed that
      untreated fish exhibited a preference for the EC at the 27- and 48-h trials, but
      (+)MK-801-treated fish did not exhibit a preference for the EC at any trial. No
      significant reduction in latency to enter the chamber was found for either
      treated or control fish. Together, the results of these experiments suggest that
      NMDA receptor antagonism (1) increases circling behavior, (2) alters swimming
      activity, and (3) impairs place preference. These findings lend further support
      for the usefulness of the zebrafish for assessing the acute and chronic exposure
      effects of water-soluble compounds on motor and cognitive functions.

PMID- 15451037
TI  - Nicotinic involvement in memory function in zebrafish.
AB  - Zebrafish are an emerging model for the study of the molecular mechanisms of
      brain function. To conduct studies of the neural bases of behavior in zebrafish,
      we must understand the behavioral function of zebrafish and how it is altered by
      perturbations of brain function. This study determined nicotine actions on memory
      function in zebrafish. With the methods that we have developed to assess memory
      in zebrafish using delayed spatial alternation (DSA), we determined the dose
      effect function of acute nicotine on memory function in zebrafish. As in rodents
      and primates, low nicotine doses improve memory in zebrafish, while high nicotine
      doses have diminished effect and can impair memory. This study shows that
      nicotine affects memory function in zebrafish much like in rats, mice, monkeys
      and humans. Now, zebrafish can be used to help understand the molecular
      mechanisms crucial to nicotine effects on memory.

PMID- 15451038
TI  - Ethanol exposure alters zebrafish development: a novel model of fetal alcohol
      syndrome.
AB  - Prenatal exposure to alcohol has been shown to produce the overt physical and
      behavioral symptoms known as fetal alcohol syndrome (FAS) in humans. Also, it is
      believed that low concentrations and/or short durations of alcohol exposure can
      produce more subtle effects. The purpose of this study was to investigate the
      effects of embryonic ethanol exposure on the zebrafish (Danio rerio) in order to
      determine whether this species is a viable animal model for studying FAS.
      Fertilized embryos were reared in varying concentrations of ethanol (1.5% and
      2.9%) and exposure times (e.g., 0-8, 6-24, 12-24, and 48-72 h postfertilization;
      hpf); anatomical measures including eye diameter and heart rate were compared
      across groups. Results found that at the highest concentration of ethanol (2.9%),
      there were more abnormal physical distortions and significantly higher mortality
      rates than any other group. Embryos exposed to ethanol for a shorter duration
      period (0-8 hpf) at a concentration of 1.5% exhibited more subtle effects such as
      significantly smaller eye diameter and lower heart rate than controls. These
      results indicate that embryonic alcohol exposure affects external and internal
      physical development and that the severity of these effects is a function of both
      the amount of ethanol and the timing of ethanol exposure. Thus, the zebrafish
      represents a useful model for examining basic questions about the effects of
      embryonic exposure to ethanol on development.

PMID- 15451039
TI  - Strain-dependent effects of developmental ethanol exposure in zebrafish.
AB  - Developmental ethanol exposure from maternal consumption of alcoholic beverages
      and many other consumer products has been linked to developmental abnormalities
      in humans and animal models. The sensitivity of an individual to ethanol-induced
      perturbation of developmental processes is strongly influenced by genetic
      factors. In this study, we show that there are strain- and dose-dependent
      differences in sensitivity to developmental ethanol exposure in zebrafish (Danio
      rerio), suggesting that genetic variation within regulatory factors, influencing
      critical developmental pathways, is responsible for these differences.
      Embryos/larvae from genetically distinct strains of zebrafish [Ekkwill (EK), AB,
      and Tuebingen (TU)] were treated with different concentrations of ethanol.
      Embryo/larval survival, neurocranial and craniofacial skeletal development, and
      CNS cell death were analyzed. EK was the most resistant strain to the
      embryolethal effects of ethanol exposure but had the greatest increase in ethanol
      induced cell death. AB survival was affected moderately, as were the neurocranial
      and craniofacial skeletal structures and ethanol-induced cell death. TU had the
      lowest survival rate but was the most resistant to alterations in neurocranial
      and craniofacial skeletal elements. No single strain is the most sensitive or the
      most resistant to any of the phenotypes examined, suggesting that alcohol
      influences each of these pathways independently. Further analysis of the
      molecular and biochemical pathways underlying the strain-dependent differences
      reported herein could lead to a significant advancement in our mechanistic
      understanding of the teratogenic effects of ethanol in humans.

PMID- 15451040
TI  - Ethanol effects on the developing zebrafish: neurobehavior and skeletal
      morphogenesis.
AB  - Exposure to ethanol during development can lead to a constellation of congenital
      anomalies, resulting in prenatal and postnatal failure to thrive, central nervous
      system (CNS) deficits, and a number of patterning defects that lead to defects in
      the cardiovascular system, facial structures, and limbs. The cellular,
      biochemical, and molecular mechanisms by which ethanol exerts its developmental
      toxicity and the genes that influence sensitivity to developmental ethanol
      exposure have yet to be discovered, despite being one of the more common
      nongenetic causes of birth defects. The zebrafish undergoes much the same
      patterning and morphogenesis as other vertebrate embryos do--including humans-
      that are distinct and cannot be studied in invertebrates. Developmental processes
      in zebrafish are affected by ethanol exposure in a dose-dependent manner,
      resulting in learning and memory deficits, cell death in the CNS, skeletal
      dysmorphogenesis, and alterations in startle reflex responses. Interestingly,
      significant ethanol effects on learning and behavioral endpoints occurred at
      concentrations well below those that induced cell death in the CNS. This work
      provides the foundation for identifying genes and pathways involved in
      developmental alcohol toxicity in vertebrates, leading to a more complete
      mechanistic understanding of fetal alcohol disorders in humans.

PMID- 15451041
TI  - Ethanol- and acetaldehyde-mediated developmental toxicity in zebrafish.
AB  - Ethanol is a well-established developmental toxicant; however, the mechanism(s)
      of this toxicity remains unclear. Zebrafish are becoming an important model
      system for the evaluation of chemical and drug toxicity. In this study, zebrafish
      embryos were utilized to compare the developmental toxicity resulting from either
      ethanol or acetaldehyde exposure. Embryos were exposed to waterborne ethanol
      concentrations for various lengths of time but encompassed the earliest stages of
      embryogenesis. The waterborne ethanol concentration that causes 50% mortality
      (LC(50)) following a 45-h ethanol exposure was approximately 340 mM (1.98% v/v).
      A number of reproducible endpoints resulted from ethanol exposure and included
      pericardial edema, yolk sac edema, axial malformations, otolith defects, delayed
      development, and axial blistering. When the exposure period was reduced, similar
      signs of toxicity were produced at nearly identical ethanol concentrations. To
      estimate the embryonic dose following a given waterborne ethanol concentration, a
      kinetic alcohol dehydrogenase (ADH) assay was adapted. The average embryonic
      ethanol dose was calculated to be a fraction of the waterborne concentration.
      Embryos exposed to waterborne acetaldehyde resulted in similar, but not
      identical, endpoints as those induced by ethanol. Embryos were however, almost
      three orders of magnitude more sensitive to acetaldehyde than to ethanol. Ethanol
      and acetaldehyde both negatively impact embryonic development; however, ethanol
      is more teratogenic based on teratogenic indices (TIs). These results demonstrate
      that the zebrafish model will provide an opportunity to further evaluate the
      mechanism of action of ethanol on vertebrate development.

PMID- 15451042
TI  - Beneficial effects of the sigma1 receptor agonists igmesine and
      dehydroepiandrosterone against learning impairments in rats prenatally exposed to
      cocaine.
AB  - In utero cocaine (IUC) exposure results in offspring rats in complex
      neurochemical and behavioral alterations, particularly affecting learning and
      memory processes. We examined here the impact of IUC exposure on memory functions
      in male and female offspring rats and report that selective sigma(1) (sigma(1))
      receptor agonists are effective in reversing the deficits. Dams received a daily
      cocaine, 20 mg/kg ip, injection between gestational days E17 to E20. Learning was
      examined in offspring between day P30 and P41 using delayed alternation in the T
      maze, water-maze learning and passive avoidance. Both male and female rats
      prenatally exposed to cocaine showed delayed alternation deficits and impairments
      of acquisition of a fixed platform position in the water maze, as shown by higher
      acquisition latencies and diminutions of time spent in the training quadrant
      during the probe test. The acquisition of a daily changing platform position also
      demonstrated impaired working memory. Finally, passive avoidance deficits were
      observed. Pretreatment with the synthetic sigma(1) agonist igmesine (0.1-1 mg/kg
      ip) or the neuroactive steroid dehydroepiandrosterone (DHEA 10-40 mg/kg ip)
      reversed the prenatal cocaine-induced learning deficits in offspring rats for
      each test. The sigma(1) antagonist BD1063 (1 mg/kg ip) failed to affect
      performances alone but blocked the igmesine and DHEA effects, confirming the
      involvement of the sigma(1) receptor. IUC exposure thus results in marked memory
      deficits, affecting spatial and nonspatial short- and long-term memories in
      juvenile male and female offspring rats. The activation of the sigma(1)
      neuromodulatory receptor allows a complete behavioral recovery of the memory
      functions in prenatally cocaine-exposed rats.

PMID- 15451043
TI  - Endocrine disruption and cognitive function in adolescent female rhesus monkeys.
AB  - Female rhesus monkeys (n=8/group) received daily oral doses of exogenous estrogen
      [diethylstilbestrol (DES), 0.5 mg/kg, methoxychlor (MXC), 25 or 50 mg/kg] for 6
      months before and after the anticipated age of menarche. Behavior was assessed
      during and for 9 months after dosing. Visual discrimination performance
      (simultaneous nonmatch-to-sample with trial-unique stimuli) conducted during
      dosing demonstrated delayed improvement and poorer performance in the MXC50
      group, with some similar effects in the DES group. Visual recognition memory,
      assessed with delays of < or = 3 s, was not apparently affected. Spatial working
      memory, assessed after dosing, also showed acquisition deficits and possible
      working memory difficulties in the MXC50 group. Spontaneous motor activity,
      monitored at 6-month intervals, was not affected by treatment. Late peak
      latencies of the auditory brainstem response (ABR) were shorter in the DES group
      6 months after treatment, suggesting long-term effects on brain. The study
      suggests that some aspects of brain function can be modified by exposure to
      exogenous estrogen during pubertal development. Although DES is a more potent
      estrogen, the high-dose MXC group was more affected behaviorally. Differential
      effects of the two agents at the estrogen receptor subtypes (ER alpha and ER
      beta) may be relevant to the differential behavioral outcomes.

PMID- 15451044
TI  - Blood manganese content at birth and cord serum prolactin levels.
AB  - Manganese (Mn) is both an essential element and, at a high dose, a potent
      neurotoxin that can interact with dopaminergic neurotransmission. Plasma
      prolactin (PRL), an indirect indicator of dopaminergic functioning, has been
      shown to vary with Mn exposure in adults, but little is known about this relation
      in the developing brain. The objective of this study was to examine the relations
      between maternal and cord Mn blood concentrations at birth and PRL cord blood
      levels. Blood Mn levels were determined in 87 pregnant women at delivery, and PRL
      was measured in the cord blood plasma. Mn cord blood concentration (mean 34.4
      microg/l, range 16.7-89.4) was significantly and positively related to cord PRL
      levels. These findings suggest that Mn accumulation in utero could contribute to
      PRL level variation in neonates, which, in turn, may influence important
      developmental parameters.

PMID- 15451045
TI  - Hippocampal antioxidant system in neonates from methylmercury-intoxicated rats.
AB  - Methylmercury (MeHg) is a well-known environmental pollutant toxic to the nervous
      tissue, particularly during development. We recently described transitory
      hippocampal changes in neonate rats prenatally exposed to MeHg. In this study, we
      evaluate oxidative stress in the hippocampus on the 1st and 30th postnatal days.
      Motor behavior (open-field, foot-fault and strength tests) of these animals also
      was studied after the 30th postnatal day. Female Wistar rats were injected with
      MeHg (5 mg/Hg/day) on the 12th, 13th and 14th gestational days. Biochemical
      parameters measured for oxidative stress were levels of the antioxidant enzymes
      superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT).
      Total antioxidant reactivity (TAR) and protein oxidation (contents of tryptophan
      and tyrosine) were also recorded. Our results showed low activities of
      antioxidant enzymes in the MeHg group at birth. SOD activity remained reduced on
      the 30th postnatal day. Moreover, a decrease of TAR and protein oxidation was
      observed only at 30 days of age. No changes were observed in the motor behavior
      of these animals. Although mercury content in hippocampus is present at
      undetectable levels at 30 days of age, we observed more persistent changes in
      oxidative balance. Our data confirm that mercury induces oxidative stress in
      hippocampus and that this alteration, particularly SOD activity, remained altered
      even when mercury was no longer present.

PMID- 15451046
TI  - Effects of drug countermeasures for space motion sickness on working memory in
      humans.
AB  - Space motion sickness (SMS) is a problem during the first 72 h of space flight
      and during transitions from different gravity environments. There currently are
      no effective drug countermeasures for SMS that also accommodate the retention of
      optimal cognitive function. This creates a dilemma for astronauts because
      cognitive skills are particularly important during gravity transitions (e.g.,
      take-off and landing). To quantify the cognitive side effects of potential drug
      countermeasures, an automated delayed matching-to-sample (DMTS) procedure was
      used to assess visual working memory before and after drug countermeasures
      (meclizine 25 mg, scopolamine 0.4 mg, promethazine 25 mg, or lorazepam 1 mg,
      given orally approximately 45 min prior to testing) and/or the induction of SMS
      by vestibular stimulation in a rotary chair (spinning). Sixty-seven normal
      healthy volunteers (mean age, in years, 26.6+/-4.8 S.D.; 24 females and 43 males)
      each participated in two test sessions, one 'off' drug and one 'on' drug.
      Spinning by itself significantly decreased task accuracy (Acc) and choice
      response speed, especially at longer recall delays. Meclizine alone had no effect
      on Acc or speed with or without spinning. Scopolamine alone decreased Acc, and
      with spinning, slowed speed. Promethazine alone had no adverse effect, but
      combined with spinning, decreased Acc and speed. Lorazepam alone decreased speed,
      and with spinning, decreased Acc. The data suggest that, at clinically useful
      doses, the rank order of the drugs with the best cognitive profiles is
      meclizine>scopolamine>promethazine>lorazepam.

PMID- 15451047
TI  - The distribution of cocaine in mice differs by age and strain.
AB  - Few studies have examined the influence of the age and the strain of mouse on the
      pharmacokinetics of psychostimulants, or the role of pharmacokinetics in age
      related differences in drug responses. The present study compared concentrations
      of cocaine, and its metabolite, benzoylecgonine (BZE), in the blood and brain of
      early (P35) and later (P42) periadolescent and adult (P63) CD-1 and C57BL/6 male
      mice 15 min after acute intraperitoneal injection of cocaine (20 mg/kg). Brain
      levels of cocaine and BZE after seven daily cocaine injections in CD-1 and
      C57BL/6 mice beginning on P35 and on P63 were also measured. P35 periadolescents
      of both strains had lower blood cocaine levels than did the adults, but only
      C57BL/6 periadolescents had lower brain cocaine levels than the adults. C57BL/6
      mice of both ages had higher blood cocaine levels than did the corresponding CD-1
      mice. Concomitant with lower cocaine levels, periadolescent CD-1 mice had higher
      blood BZE levels than the adults, suggesting that periadolescents may metabolize
      cocaine faster. Brain cocaine levels in P42 C57BL/6 mice were similar to those of
      adults. Cocaine-induced activity did not differ between periadolescent and adult
      CD-1 mice after a single injection of cocaine, whereas periadolescent C57BL/6
      mice had lower activity levels than did the adults after a single cocaine
      injection. Periadolescent CD-1 mice exhibited higher levels of locomotor activity
      following cocaine injection than did periadolescent C57BL/6 mice. Following
      chronic cocaine administration, cocaine and BZE levels in the brains of
      periadolescent and adult mice did not differ from each other in either strain.
      However, brain cocaine levels at both ages were lower in CD-1 mice than in
      C57BL/6 mice. In conclusion, the age and the strain of mouse significantly affect
      the levels of cocaine obtained in brain and blood following acute administration.
      Our data are consistent with the notion that CD-1 and C57BL/6 mice metabolize
      cocaine faster during the early periadolescent period than as adults.
      Furthermore, potentially important strain differences between CD-1 and C57BL/6
      mice were noted in cocaine levels following acute and chronic cocaine
      administration, and in locomotor activity following acute cocaine administration.

PMID- 15451048
TI  - Absorption and clearance of +/-3,4-methylenedioxymethamphetamine from the plasma
      of neonatal rats.
AB  - A limited number of studies exist describing the effects of +/-3,4
      methylenedioxymethamphetamine (MDMA) during perinatal development, although the
      number of MDMA users has increased dramatically, and this increase is greatest in
      people of child-bearing age. Previous experimental studies show that exposure to
      MDMA during part of the third trimester-equivalent (postnatal days P1-20 in rats)
      cause two distinct types of learning and memory deficits (sequential and spatial)
      if exposed on P11-20, but not if exposure occurs on P1-10. In the present study,
      we examined differences in the ability of neonatal rats to eliminate MDMA. Rat
      offspring were given a single dose of 20 mg/kg MDMA on either P1 or 11, and
      plasma was collected at 1 of 10 time points during a 10-h period. MDMA
      concentrations were assessed by liquid chromatography/mass spectrometry (LC/MS).
      Indices of absorption did not differ as a function of exposure age. Exposure age
      differences in the clearance rate and half-life of MDMA were observed, such that
      the P1-treated animals had a significantly more rapid clearance and a shorter
      half-life than P11-treated animals did. These changes are in the same direction
      as the behavioral differences reported previously between P1-10 and P11-20 MDMA
      exposure groups. However, the pharmacokinetic differences were not commensurate
      with the behavioral changes in that the clearance differences at the two ages are
      quantitative whereas the behavioral differences were qualitative (no effects from
      P1-10 exposure and large effects from P11-20). Although the data do not suggest a
      mechanism for the learning deficits, they indicate that pharmacokinetic
      differences may contribute to the effects seen when exposure is begun on P11.

PMID- 15451049
TI  - Sensitivity of zebrafish to environmental toxins implicated in Parkinson's
      disease.
AB  - Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic
      (DA) neurons in the substantia nigra and movement defects, including
      bradykinesia, tremor, and postural imbalance. Whereas the etiology and
      pathogenesis of PD is still poorly understood, studies in animal models are
      providing important insights. One valuable type of animal model for PD is
      established by treating animals with PD-inducing neurotoxins, including 1-methyl
      4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), rotenone, and paraquat. These
      neurotoxins are thought to inhibit mitochondrial complex I activity leading to
      oxidative stress, impaired energy metabolism, proteasomal dysfunction, and,
      eventually, dopamine neuronal loss. However, the genes and pathways that underlie
      the neurotoxicity of these agents are not known. In this study, we explored the
      effect of MPTP, rotenone, and paraquat in both adult and larval zebrafish, which
      are highly amenable to genetic analysis that can lead to the identification of
      the underlying genes and pathways. Here, we report that adult zebrafish display
      behavioral alterations, including decreased locomotor activity in response to
      MPTP, whereas larval zebrafish exhibited developmental, behavioral, and DA
      sensitivity to these agents. Taken together, these findings suggest that
      zebrafish could be a valuable model for genetically dissecting the molecular
      mechanisms underlying the neurotoxicity of PD-inducing agents.

PMID- 15451050
TI  - Introduction to serial review on heme oxygenase in human disease.

PMID- 15451051
TI  - The role of heme oxygenase-1 promoter polymorphisms in human disease.
AB  - Heme oxygenase (HO) seems to be a novel protective factor with potent anti
      inflammatory, anti-oxidant, and anti-proliferative effects. HO-1, the inducible
      isoform, is expressed in various tissues and is upregulated by multiple stimuli.
      However, humans differ quantitatively in their ability to mount an HO-1 response,
      modulated by two potentially functional polymorphisms in the HO-1 gene promoter
      region. From several studies it seems that the ability of a patient with certain
      genotypes to respond strongly in terms of upregulating HO-1 may be an important
      endogenous protective factor. In the present article we systematically review the
      hitherto published evidence that promoter polymorphisms in the HO-1 gene exert
      functional importance by influencing the level of HO-1 expression in different
      organ systems.

PMID- 15451052
TI  - Alternative nitric oxide-producing substrates for NO synthases.
AB  - Nitric oxide (NO) is a key inter- and intracellular molecule involved in the
      maintenance of vascular tone, neuronal signaling, and host response to infection.
      The biosynthesis of NO in mammals involves a two-step oxidation of L-arginine (L
      Arg) to citrulline and NO catalyzed by a particular class of heme-thiolate
      proteins, called NO-synthases (NOSs). The NOSs successively catalyze the Nomega
      hydroxylation of the guanidine group of L-Arg with formation of Nomega-hydroxy-L
      arginine (NOHA) and the oxidative cleavage of the CN(OH) bond of NOHA with
      formation of citrulline and NO. During the last decade, a great number of
      compounds bearing a CNH or CNOH function have been synthesized and studied as
      possible NO-producing substrates of recombinant NOSs. This includes derivatives
      of L-Arg and NOHA, N-alkyl (or aryl) guanidines, N,N'- or N,N-disubstituted
      guanidines, N-alkyl (or aryl) N'-hydroxyguanidines, N- (or O-) disubstituted N'
      hydroxyguanidines, as well as amidoximes, ketoximes, and aldoximes. However, only
      those involving the NHC(NH2)=NH (or NOH) moiety have led to a significant
      formation of NO. All the N-monosubstituted N'-hydroxyguanidines that are well
      recognized by the NOS active site lead to NO with catalytic efficiences (kcat/Km)
      up to 50% of that of NOHA. This is the case of many N-aryl and N-alkyl N'
      hydroxyguanidines, provided that the aryl or alkyl substituent is small enough to
      be accommodated by a NOS hydrophobic site located in close proximity of the NOS
      "guanidine binding site." As far as N-substituted guanidines are concerned, few
      compounds bearing a small alkyl group have been found to act as NO-producing
      substrates. The kcat value found for the best compound may reach 55% of the kcat
      of L-Arg oxidation. However, the best catalytic efficiency (kcat/Km) that was
      obtained with N-(4,4,4-trifluorobutyl) guanidine is only 100-fold lower than that
      of L-Arg. In a general manner, NOS II is a better catalyst that NOS I and III for
      the oxidation of exogenous guanidines and N-hydroxyguanidines to NO. This is
      particularly true for guanidines as the ones acting as substrates for NOS II have
      been found to be almost inactive for NOS I and NOS III. Thus, a good NO-producing
      guanidine substrate for the two latter isozymes remains to be found.

PMID- 15451053
TI  - Nitrates and NO release: contemporary aspects in biological and medicinal
      chemistry.
AB  - Nitroglycerine has been used clinically in the treatment of angina for 130 years,
      yet important details on the mechanism of action, biotransformation, and the
      associated phenomenon of nitrate tolerance remain unanswered. The biological
      activity of organic nitrates can be said to be nitric oxide mimetic, leading to
      recent, exciting progress in realizing the therapeutic potential of nitrates.
      Unequivocally, nitroglycerine and most other organic nitrates, including NO
      NSAIDs, do not behave as NO donors in the most fundamental action: in vitro
      activation of sGC to produce cGMP. The question as to whether the biological
      activity of nitrates results primarily or exclusively from NO donation will not
      be satisfactorily answered until the location, the apparatus, and the mechanism
      of reduction of nitrates to NO are defined. Similarly, the therapeutic potential
      of nitrates will not be unlocked until this knowledge is attained. Aspects of the
      therapeutic and biological activity of nitrates are reviewed in the context of
      the chemistry of nitrates and the elusive efficient 3e- reduction required to
      generate NO.

PMID- 15451054
TI  - T cell receptor stimulation, reactive oxygen species, and cell signaling.
AB  - In the immune system, much of the focus on reactive oxygen species (ROS) has been
      regarding their role in antimicrobial defense as part of the innate immune
      system. In addition to this role, it is now becoming clear that ROS are used by
      cells of the adaptive immune system as regulators of signal transduction by cell
      surface receptors. The activation of T lymphocytes through their specific antigen
      receptor [T cell receptor (TCR)] is vital in regulating the immune response. Much
      experimental evidence has suggested that activation of T cells is redox dependent
      and recent studies have shown that engagement of the TCR induces rapid production
      of ROS. This review examines the evidence for TCR-stimulated generation of ROS
      and discusses the role(s) of receptor-stimulated ROS production in T cell signal
      transduction and gene expression.

PMID- 15451055
TI  - Human glutamate cysteine ligase gene regulation through the electrophile response
      element.
AB  - Glutathione (GSH) is the primary nonprotein thiol in the cell. It has many
      important roles in cell function, including regulating redox-dependent signal
      transduction pathways. The content of GSH within the cell varies with stress. In
      many cases, a process involving GSH synthesis results in adaptation to subsequent
      stressors. Sustained increases in GSH content are controlled primarily through
      induction of two genes, Gclc and Gclm, leading to the synthesis of the rate
      limiting enzyme for GSH synthesis, glutamate cysteine ligase. Each of these genes
      in humans has a number of putative enhancer elements in their promoters. Overall,
      the most important element in both Gclc and Gclm expression is the electrophile
      response element. We review the evidence that has led to this conclusion and the
      implications for the redox-dependent regulation of this critical intracellular
      antioxidant.

PMID- 15451056
TI  - Intracellular pH-dependent peroxynitrite-evoked synergistic death of glucose
      deprived astrocytes.
AB  - Previously, we reported that glucose-deprived astrocytes were highly vulnerable
      to peroxynitrite (ONOO-). Here we demonstrate that the increased vulnerability
      caused by glucose deprivation and ONOO- depends on intracellular pH. The ONOO-
      releasing reagent 3-morpholinosydnonimine (SIN-1) markedly induced the release of
      lactate dehydrogenase (LDH, the marker of cytotoxicity) in glucose-deprived
      astrocytes. Morphological studies and caspase activity assay showed that
      astrocytes treated together with glucose deprivation and ONOO- died mostly in a
      necrotic mode. Alkalinization of pH from 7.4 to 7.8 increased LDH release,
      whereas acidification from pH 7.4 to 7.0 decreased it. However, intracellular pH
      (pHi), not extracellular pH (pHe), appeared to play a critical role in the
      synergistic death. Thus, without a change in pHe (7.4) cytosolic acidification by
      a weak acid salt, sodium acetate, and a Na+/H+ antiporter inhibitor, amiloride,
      reduced LDH release. In contrast, a weak base, NH4Cl, and a Na+/H+ antiporter
      stimulator, monensin, increased pHi and greatly enhanced LDH release. The
      augmented death was found to be due, in part, to the preceding decrease in the
      level of reduced glutathione, the ONOO- scavenger, and collapse of the
      mitochondrial transmembrane potential at alkaline pH.

PMID- 15451057
TI  - Molecular characterization of two CuZn-superoxide dismutases in a sea anemone.
AB  - Cnidarians living in symbiosis with photosynthetic cells--called zooxanthellae-
      are submitted to high oxygen levels generated by photosynthesis. To cope with
      this hyperoxic state, symbiotic cnidarians present a high diversity of superoxide
      dismutases (SOD) isoforms. To understand better the mechanism of resistance of
      cnidarian hosts to hyperoxia, we studied copper- and zinc-containing SOD
      (CuZnSOD) from Anemonia viridis, a temperate symbiotic sea anemone. We cloned two
      CuZnSOD genes that we call AvCuZnSODa and AvCuZnSODb. Their molecular analysis
      suggests that the AvCuZnSODa transcript encodes an extracellular form of CuZnSOD,
      whereas the AvCuZnSODb transcript encodes an intracellular form. Using in situ
      hybridization, we showed that both AvCuZnSODa and AvCuZnSODb transcripts are
      expressed in the endodermal and ectodermal cells of the sea anemone, but not in
      the zooxanthellae. The genomic flanking sequences of AvCuZnSODa and AvCuZnSODb
      revealed different putative binding sites for transcription factors, suggesting
      different modes of regulation for the two genes. This study represents a first
      step in the understanding of the molecular mechanisms of host animal resistance
      to permanent hyperoxia status resulting from the photosynthetic symbiosis.
      Moreover, AvCuZnSODa and AvCuZnSODb are the first SODs cloned from a diploblastic
      animal, contributing to the evolutionary understanding of SODs.

PMID- 15451058
TI  - Antioxidant effect of zinc in humans.
AB  - Oxidative stress is known to be an important contributing factor in many chronic
      diseases. We tested the hypothesis that in healthy normal volunteers zinc acts as
      an effective anti-inflammatory and antioxidant agent. Ten normal volunteers were
      administered daily oral zinc supplementation (45 mg zinc as gluconate) and 10
      volunteers received placebo for 8 weeks. Plasma zinc, MDA, HAE, and 8-OHdG
      levels; LPS-induced TNF-alpha and IL-1beta mRNA; and ex vivo TNF-alpha-induced NF
      kappaB activity in mononuclear cells (MNC) were determined before and after
      supplementation. In subjects receiving zinc, plasma levels of lipid peroxidation
      products and DNA adducts were decreased, whereas no change was observed in the
      placebo group. LPS-stimulated MNC isolated from zinc-supplemented subjects showed
      reduced mRNA for TNF-alpha and IL-1beta compared to placebo. Ex vivo, zinc
      protected MNC from TNF-alpha-induced NF-kappaB activation. In parallel studies
      using HL-60, a promyelocytic cell line, we observed that zinc enhances the
      upregulation of mRNA and DNA-specific binding for A20, a transactivating factor
      which inhibits the activation of NF-kappaB. Our results suggest that zinc
      supplementation may lead to downregulation of the inflammatory cytokines through
      upregulation of the negative feedback loop A20 to inhibit induced NF-kappaB
      activation. Zinc administration to human subjects with conditions associated with
      increased oxidative stress should be explored.

PMID- 15451059
TI  - A biologically effective fullerene (C60) derivative with superoxide dismutase
      mimetic properties.
AB  - Superoxide, a potentially toxic by-product of cellular metabolism, may contribute
      to tissue injury in many types of human disease. Here we show that a tris-malonic
      acid derivative of the fullerene C60 molecule (C3) is capable of removing the
      biologically important superoxide radical with a rate constant (k(C3)) of 2 x
      10(6) mol(-1) s(-1), approximately 100-fold slower than the superoxide dismutases
      (SOD), a family of enzymes responsible for endogenous dismutation of superoxide.
      This rate constant is within the range of values reported for several manganese
      containing SOD mimetic compounds. The reaction between C3 and superoxide was not
      via stoichiometric "scavenging," as expected, but through catalytic dismutation
      of superoxide, indicated by lack of structural modifications to C3, regeneration
      of oxygen, production of hydrogen peroxide, and absence of EPR-active
      (paramagnetic) products, all consistent with a catalytic mechanism. A model is
      proposed in which electron-deficient regions on the C60 sphere work in concert
      with malonyl groups attached to C3 to electrostatically guide and stabilize
      superoxide, promoting dismutation. We also found that C3 treatment of Sod2(-/-)
      mice, which lack expression of mitochondrial manganese superoxide dismutase
      (MnSOD), increased their life span by 300%. These data, coupled with evidence
      that C3 localizes to mitochondria, suggest that C3 functionally replaces MnSOD,
      acting as a biologically effective SOD mimetic.

PMID- 15451060
TI  - Hydroxyl radical oxidation of cytochrome c by aerobic radiolysis.
AB  - The reaction of radiolytically generated *OH with cytochrome c was investigated
      by mass spectrometry. Tryptic digestion and characterization of the oxidized
      peptides by MALDI-TOF and ESI tandem mass spectrometry identified eight different
      amino acid residues with oxidized side chains with no cleavage of the protein
      detected. Solvent-accessible aromatic and methionine residues are the most
      susceptible to oxidation by *OH. These results support the careful use of *OH in
      characterizing protein surfaces. Dose-response studies identified the residues
      most prone to oxidation to be Phe-36, Phe-46, and Met-80. Hydroxylation of Phe-36
      and Phe-46 should serve as indicators of the presence of *OH in the mitochondrial
      intermembrane space. Using solutions containing 50 at.% (18)O, our study also
      provides a novel method of determining the source of oxygen during *OH-mediated
      oxidation of proteins and contributes to identification of the modified residue
      type, with Phe>Tyr>Met in (18)O incorporation. During aerobic radiolysis, UV-vis
      spectroscopy indicates that ferrocytochrome c reaches a steady state concomitant
      with reduction of the heme.

PMID- 15451061
TI  - Xanthine oxidoreductase is present in bile ducts of normal and cirrhotic liver.
AB  - Xanthine oxidoreductase (XOR) is a widely distributed enzyme, involved in the
      metabolism of purines, which generates superoxide and is thought to be involved
      in free radical-generated tissue injury. It is present at high concentrations in
      the liver, from where it may be released during liver injury into the
      circulation, binding to vascular endothelium and causing vascular dysfunction.
      The cellular localization of the enzyme, essential to understanding its function,
      is, however, still debated. The present study has used a highly specific mouse
      monoclonal antibody to define the cellular distribution of XOR in normal and
      cirrhotic human liver. As shown previously, XOR is present in hepatocytes.
      However, the novel finding of this study is that XOR is present in bile duct
      epithelial cells, where it is concentrated toward the luminal surface. Moreover,
      in liver disease, proliferating bile ducts are also strongly positive for XOR.
      These findings suggest that the enzyme is secreted into bile, and this was
      confirmed by analysis of human and rat bile. Xanthine oxidase activity was 10 to
      20-fold higher in liver tissue obtained from patients with liver disease, than in
      healthy liver. We conclude that XOR is expressed primarily in hepatocytes, but is
      also present in bile duct epithelial cells and is secreted into bile. Its role in
      bile is unknown but it may be involved in innate immunity of the bowel muscosa.

PMID- 15451062
TI  - Prion protein protects against DNA damage induced by paraquat in cultured cells.
AB  - Exposure of cells to paraquat leads to production of superoxide anion (O2*-).
      This reacts with hydrogen peroxide to give the hydroxyl radical (*OH), leading to
      lipid peroxidation and cell death. In this study, we investigated the effects of
      cellular prion protein (PrPC) overexpression on paraquat-induced toxicity by
      using an established model system, rabbit kidney epithelial A74 cells, which
      express a doxycycline-inducible murine PrPC gene. PrPC overexpression was found
      to significantly reduce paraquat-induced cell toxicity, DNA damage, and
      malondialdehyde acid levels. Superoxide dismutase (total SOD and CuZn-SOD) and
      glutathione peroxidase activities were higher in doxycycline-stimulated cells.
      Our findings clearly show that PrPC overexpression plays a protective role
      against paraquat toxicity, probably by virtue of its superoxide dismutase-like
      activity.

PMID- 15451063
TI  - Sp3 repression of polymorphic human NRH:quinone oxidoreductase 2 gene promoter.
AB  - Human NRH:quinone oxidoreductase 2 (NQO2) gene-containing 29-bp
      deletion/insertion polymorphic promoters were found to be associated with
      susceptibility to Parkinson's disease. Here, we demonstrate that the NQO2 gene is
      differentially expressed by the polymorphic promoters in human fibroblasts and
      Hep-G2 cells transfected with NQO2 gene reporter constructs. Promoter containing
      the 29-bp insertion polymorphism demonstrated significantly lower NQO2 gene
      expression. Deletion mutagenesis and DNase I footprinting analysis of the
      promoter without the 29-bp insertion identified three protected regions (region
      A, B, and C). Band- and supershift and transfection assays showed binding of
      transcription factor Sp1 to regions A and B, which regulated expression of the
      NQO2 gene. Similar studies of the NQO2 gene promoter with the 29-bp insertion
      polymorphism showed that regions A and C were identical and contributed similarly
      as in the promoter without the 29-bp insertion to NQO2 gene expression. However,
      region B was found to be inserted with 29-bp DNA element and bound to both Sp1
      and Sp3. Binding of Sp3 led to repression of NQO2 gene transcription by the
      promoter containing the 29-bp insertion polymorphism. These studies also suggest
      that alterations in NQO2 activity might be an important factor in susceptibility
      to Parkinson's disease.

PMID- 15451064
TI  - Scavenging of reactive nitrogen species by oxygenated hemoglobin: globin radicals
      and nitrotyrosines distinguish nitrite from nitric oxide reaction.
AB  - The reaction of *NO and NO2- with hemoglobin (Hb) is of pivotal importance to
      blood vessel function. Both species show at least two different reactions with
      Fe2+ Hb: one with deoxygenated Hb, in which the biological properties of *NO are
      preserved, and another with oxygenated hemoglobin (oxyHb), in which both species
      are oxidizes to NO3-. In this study we compared the oxidative reactions of *NO
      and NO2- and, in particular, the radical intermediates formed during
      transformation to NO3-. The reaction of NO2- with oxyHb was accelerated at high
      heme concentrations and produced stoichiometric amounts of NO3-. Direct EPR and
      spin trapping studies showed that NO2-, but not *NO, induced the formation of
      globin Tyr-, Trp-, and Cys-centered radicals. MS studies provided evidence of the
      formation of approximately 2% nitrotyrosine in both the alpha and beta subunits,
      suggesting that *NO2 diffuses in part away from the heme and reacts with Tyr
      radicals. No nitrotyrosines were detected in the reaction of *NO with oxyHb.
      Collectively, these results indicate that NO2- reaction with oxyHb causes an
      oxidative challenge not observed with *NO. The differences in oxidation
      mechanisms of *NO and NO2- are discussed.

PMID- 15451065
TI  - Sp1 and Sp3 transcription factors mediate trichostatin A-induced and basal
      expression of extracellular superoxide dismutase.
AB  - Extracellular superoxide dismutase (EC-SOD) is the major extracellular
      antioxidant enzyme and may play a critical role in the pathogenesis of a variety
      of pulmonary, neurological, and cardiovascular diseases. We report here that
      exposure to the deacetylase inhibitor trichostatin A (TSA) induces EC-SOD mRNA
      levels in mIMCD3 and Hepa 1-6 cells, but reduces EC-SOD mRNA levels in MLg cells.
      To determine the molecular mechanism of TSA-mediated EC-SOD gene regulation, we
      analyzed EC-SOD's proximal promoter region, which revealed two previously unknown
      but putative Sp1 cis elements. Transfection of systematically truncated 5'
      flanking sequences revealed that the second Sp1 binding site contributes up to
      70% of the constitutive EC-SOD promoter activity. Binding of Sp1 and Sp3
      transcription factors to this region was confirmed by DNase I footprinting,
      electrophoretic mobility shift assay, super-shift assay, and chromatin
      immunoprecipitation. A dominant-negative Sp1 construct considerably reduced EC
      SOD promoter activity in mammalian cells, whereas coexpression of Sp1 and Sp3
      greatly enhanced reporter activity in SL2 cells. An EC-SOD promoter-reporter
      construct showed from 5- to 14-fold induction after exposure to TSA, whereas
      deletion of the Sp1 binding site significantly reduced reporter activation. These
      results are consistent with Sp1/Sp3 transcription factors providing essential TSA
      dependent and basal transcription of the EC-SOD gene and may represent a novel
      pharmacological pathway for regulating EC-SOD levels in tissue.

PMID- 15451066
TI  - Role of glutathione in the adaptive tolerance to H2O2.
AB  - Endogenous antioxidant defense systems are enhanced by various physiological
      stimuli including sublethal oxidative challenges, which induce tolerance to
      subsequent lethal oxidative injuries. We sought to evaluate the contributions of
      catalase and the glutathione system to the adaptive tolerance to H2O2. For this
      purpose, H9c2 cells were stimulated with 100 microM H2O2, which was the maximal
      dose at which no significant acute cell damage was observed. Twenty-four hours
      after stimulation, control and pretreated cells were challenged with a lethal
      concentration of H2O2 (300 microM). Compared with the control cells, pretreated
      cells were significantly tolerant of H2O2, with reduced cell lysis and improved
      survival rate. In pretreated cells, glutathione content increased to 48.20 +/-
      6.38 nmol/mg protein versus 27.59 +/- 2.55 nmol/mg protein in control cells, and
      catalase activity also increased to 30.82 +/- 2.64 versus 15.46 +/- 1.29 units/mg
      protein in control cells, whereas glutathione peroxidase activity was not
      affected. Increased glutathione content was attributed to increased gamma
      glutamylcysteine synthetase activity, which is known as the rate-limiting enzyme
      of glutathione synthesis. To elucidate the relative contribution of the
      glutathione system and catalase to tolerance of H2O2, control and pretreated
      cells were incubated with specific inhibitors of gamma-glutamyl cysteine
      synthetase (L-buthionine sulfoximine) or catalase (3-amino-1,2,4-triazole), and
      challenged with H2O2. Cytoprotection by the low-dose H2O2 pretreatment was almost
      completely abolished by L-buthionine sulfoximine, while it was preserved after 3
      amino-1,2,4-triazole treatment. From these results, it is concluded that both the
      glutathione system and catalase can be enhanced by H2O2 stimulation, but
      increased glutathione content rather than catalase activity was operative in the
      tolerance of lethal oxidative stress.

PMID- 15451067
TI  - Ascorbate protects against impaired arteriolar constriction in sepsis by
      inhibiting inducible nitric oxide synthase expression.
AB  - Compromised microvascular responsiveness is one of the key factors associated
      with mortality of septic patients. The present study addresses the mechanism of
      protection by ascorbate against impaired vasoconstriction in septic mice. Sepsis
      (i.e., cecal ligation and puncture (CLP) model) elevated both plasma protein
      carbonyl (i.e., an index of oxidative stress) and plasma nitrite/nitrate (NOx)
      levels, reduced baseline mean arterial blood pressure (MABP), and inhibited the
      MABP pressor response to angiotensin II (Ang II) at 6 h post-CLP. At the
      microvascular level, sepsis increased the inducible nitric oxide synthase (iNOS)
      mRNA level in cremaster muscle arterioles (18-25 microm diameter) at 3 h post
      CLP, and impaired vasoconstriction to Ang II in these arterioles at 6 h post-CLP.
      At 24 h post-CLP, sepsis resulted in 9% survival. An intravenous bolus of
      ascorbate (200 mg/kg body wt) given 30 min prior to CLP prevented the protein
      carbonyl and NOx increases, partially restored the baseline arterial pressure,
      and completely protected against all arteriolar iNOS mRNA increases, arteriolar
      constriction hyporesponsiveness, and pressor response impairment. Survival
      increased to 65%. In septic mice, iNOS gene knockout resulted in protection of
      arteriolar constriction and pressor responses identical to that provided by
      ascorbate. Ascorbate bolus given 3 h post-CLP protected against the increase in
      plasma NOx concentration and against the pressor response impairment. We conclude
      that ascorbate may protect arteriolar vasoconstrictor responsiveness in sepsis by
      inhibiting excessive NO production.

PMID- 15451070
TI  - Effect of nutrient intake during pregnancy on fetal and placental growth and
      vascular development.
AB  - Remarkable diversity of size and health of offspring exists after normal
      pregnancies. When pregnancies are complicated by an extrinsic variable such as
      inappropriate maternal nutrition, birth weight and health of the neonate are
      substantially affected. The placenta is the organ through which respiratory
      gases, nutrients, and wastes are exchanged between the maternal and fetal
      systems. Thus, transplacental exchange provides for all the metabolic demands of
      fetal growth. Transplacental exchange is dependent upon uterine and umbilical
      blood flow, and blood flow rates are in turn dependent in large part upon
      vascularization of the placenta. Therefore, factors that influence placental
      vascular development will have a dramatic impact on fetal growth and development,
      and thereby on neonatal mortality and morbidity. Recent work from our
      laboratories has focused on the effects of nutrient intake during pregnancy on
      placental growth and vascular development. Both nutrient restriction of the adult
      dam and overnourishment of the adolescent dam during pregnancy suppress placental
      cell proliferation and vascularity. Furthermore, placental expression of
      angiogenic factors and their receptors, factors that are known to affect vascular
      growth, are perturbed by level of nutrition. Studies in this area will lead to
      improved methods to manage nutritionally-compromised pregnancies.

PMID- 15451068
TI  - Molecular mechanism of diclofenac-induced apoptosis of promyelocytic leukemia:
      dependency on reactive oxygen species, Akt, Bid, cytochrome and caspase pathway.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) induce apoptosis in a variety of
      cells, but the mechanism of this effect has not been fully elucidated. We report
      that diclofenac, a NSAID, induces growth inhibition and apoptosis of HL-60 cells
      through modulation of mitochondrial functions regulated by reactive oxygen
      species (ROS), Akt, caspase-8, and Bid. ROS generation occurs in an early stage
      of diclofenac-induced apoptosis preceding cytochrome c release, caspase
      activation, and DNA fragmentation. N-Acetyl-L-cysteine, an antioxidant,
      suppresses ROS generation, Akt inactivation, caspase-8 activation, and DNA
      fragmentation. Cyclic AMP, an inducer of Akt phosphorylation, suppresses Akt
      inactivation, Bid cleavage, and DNA fragmentation. LY294002, a PI3 kinase
      inhibitor, enhances Akt inactivation and DNA fragmentation. Ac-IETD-CHO, a
      caspase-8 inhibitor, suppresses Bid cleavage and DNA fragmentation. z-VAD-fmk, a
      universal caspase inhibitor, but not cyclosporin A (CsA), an inhibitor of
      mitochondrial membrane permeability transition, suppresses DNA fragmentation.
      These results suggest the sequential mechanism of diclofenac-induced apoptosis of
      HL-60 cells: ROS generation suppresses Akt activity, thereby activating caspase
      8, which stimulates Bid cleavage and induces cytochrome c release and the
      activation of caspase-9 and-3 in a CsA-insensitive mechanism. Furthermore, we
      found that 2-methoxyestradiol (2-ME), a superoxide dismutase inhibitor,
      significantly enhances diclofenac-induced apoptosis; that is, diclofenac combined
      with 2-ME may have therapeutic potential in the treatment of human leukemia.

PMID- 15451071
TI  - Basic principles of muscle development and growth in meat-producing mammals as
      affected by the insulin-like growth factor (IGF) system.
AB  - This presentation aims to describe how the basic events in prenatal muscle
      development and postnatal muscle growth are controlled by the insulin-like growth
      factor system (IGF). The prenatal events (myogenesis) cover the rate of
      proliferation, the rate and extent of fusion, and the differentiation of three
      myoblast populations, giving rise to primary fibers, secondary fibers, and a
      satellite cell population, respectively. The number of muscle fibers, a key
      determinant of the postnatal growth rate, is fixed late in gestation. The
      postnatal events contributing to myofiber hypertrophy comprise satellite cell
      proliferation and differentiation, and protein turnover. Muscle cell cultures
      produce IGFs and IGF binding proteins (IGFBPs) in various degrees depending on
      the origin (species, muscle type) and state of development of these cells,
      suggesting an autocrine/paracrine mode of action of IGF-related factors. In vivo
      studies and results based on cell lines or primary cell cultures show that IGF-I
      and IGF-II stimulate both proliferation and differentiation of myoblasts and
      satellite cells in a time and concentration-dependent way, via interaction with
      type I IGF receptors. However, IGF binding proteins (IGFBP) may either inhibit or
      potentiate the stimulating effects of IGFs on proliferation or differentiation.
      During postnatal growth in vivo or in fully differentiated muscle cells in
      culture, IGF-I stimulates the rate of protein synthesis and inhibits the rate of
      protein degradation, thereby enhancing myofiber hypertrophy. The possible roles
      and actions of the IGF system in regulating and determining muscle growth as
      affected by developmental stage and age, muscle type, feeding levels, treatment
      with growth hormone and selection for growth performance are discussed.

PMID- 15451072
TI  - Regulation of development and metabolism of adipose tissue by growth hormone and
      the insulin-like growth factor system.
AB  - White adipose tissue plays a key role in the regulation of the energy balance of
      vertebrates. This tissue is also now recognized to secrete a variety of factors
      such as leptin, which is thought to be involved in the modulation of adipose
      mass. Unlike other tissues, adipose tissue mass has considerable capacity to
      expand. The review deals primarily on the regulation of development and
      metabolism of adipose tissue by growth hormone (GH) and the insulin-like growth
      factor (IGF) system, with a special focus on the pig. The anti-insulin effects of
      GH are well-documented in pigs as in other species. In vitro exposure of adipose
      precursor cells to GH leads to a decrease in differentiation of those cells in
      pigs, in contrast to data obtained in murine cell lines. In vivo treatment and
      prolonged in vitro incubation of adipose tissue or isolated adipocytes with GH
      result in a decrease in glucose transport and lipogenesis, especially at the
      level of the fatty acid synthase gene, resulting in a reduction of the lipid
      content and adipose tissue mass. The mechanism by which GH antagonizes insulin
      stimulation of lipogenesis is still unresolved, as it is not mediated by protein
      kinase A, protein kinase C and Janus kinase-2 at the signaling level, or upstream
      stimulatory factor 1 or sterol regulatory element binding protein-1 at the
      transcriptional level. GH is apparently the main regulator of IGF-I mRNA
      expression in adipose tissue, however, the effects of IGF-I on this tissue are
      rather unclear.

PMID- 15451073
TI  - The role of IGFBP-5 in mammary gland development and involution.
AB  - Insulin-like growth factor-I (IGF-I) plays an important role as a survival factor
      during mammary gland development and remodelling during involution of the
      mature/lactating mammary gland, and elevated concentrations have been associated
      with increased risk of breast cancer. The actions of IGF-I are modulated by a
      family of binding proteins (IGFBPs) and we have shown that IGFBP-5 is associated
      with cell death in the mammary gland and more recently provided the first
      evidence that it is causally related to apoptosis of the mammary gland. A
      transgenic mouse expressing IGFBP-5 on a mammary-specific promoter led to
      impaired mammary development involving inhibition of IGF-signalling and involving
      members of the Bcl-2 family. Subsequent studies in vitro and in vivo using
      exogenous IGFBP-5 treatment have added support to this concept. Although the
      effects of IGFBP-5 did appear to involve inhibition of IGF action, a role for IGF
      independent effects cannot be ruled out. Such IGF-independent effects involve
      potential interactions with components of the extracellular matrix involved in
      tissue remodelling including plasminogen activator inhibitor-1 (PAI-1). In
      addition, intracellular events involving nuclear localisation of IGFBP-5 have
      been shown to have the ability to inhibit cell proliferation. Thus, IGFBP-5 seems
      important for regulating both apoptosis and cell proliferation in the mammary
      gland during development and post-lactation involution.

PMID- 15451074
TI  - Effects of maternal nutrition and porcine growth hormone (pGH) treatment during
      gestation on endocrine and metabolic factors in sows, fetuses and pigs, skeletal
      muscle development, and postnatal growth.
AB  - Prenatal growth is very complex and a highly integrated process. Both maternal
      nutrition and the maternal somatotropic axis play a significant role in
      coordinating nutrient partitioning and utilization between maternal, placental
      and fetal tissues. Maternal nutrition may alter the nutrient concentrations and
      in turn the expression of growth regulating factors such as IGFs and IGFBPs in
      the blood and tissues, while GH acts in parallel via changing IGFs/IGFBPs and
      nutrient availability. The similarity in the target components implies that
      maternal nutrition and the somatotropic axis are closely related to each other
      and may induce similar effects on placental and fetal growth. Severe restriction
      of nutrients throughout gestation has a permanent negative effect on fetal and
      postnatal growth, whereas the effects of both temporary restriction and feeding
      above requirements during gestation seem to be of transitional character.
      Advantages in fetal growth gained by maternal growth hormone treatment during
      early to mid-gestation are not maintained to term, whereas treatment during late
      or greatest part of gestation increases progeny size at birth, which could be of
      advantage for postnatal growth. This review summarizes the available knowledge on
      the effects of different maternal feeding strategies and maternal GH
      administration during pregnancy and their interactions on metabolic and hormonal
      (especially IGFs/IGFBPs) status in the feto-maternal unit, skeletal muscle
      development and growth of the offspring in pigs.

PMID- 15451075
TI  - Molecular genetic and physiologic background of the growth hormone-IGF-I axis in
      relation to breeding for growth rate and leanness in pigs.
AB  - The GH-IGF-I axis is of major importance for the regulation of body growth and
      composition, and cellular proliferation and differentiation processes. Selective
      breeding aiming to improve growth rate and/or body composition is accompanied by
      changes of the GH-IGF-I axis. Research aiming to elucidate the genetic and
      physiologic mechanism(s) underlying these changes may best use single-trait
      selection lines. Two such pig selection lines, one for growth rate and one for
      high lean content, were used in experiments to investigate the mechanisms of the
      GH-IGF-I axis change during selection. This contribution reviews the selection
      related changes in the GH-IGF-I axis as the consequences of selection for whole
      body growth rate or body composition and effects on local tissue growth rate. A
      model explaining the observed effects and consequences for the pressure on the
      physiology is presented. In short, selection related demand for GH induces GH
      synthesis until a limit is reached. After that the pulsatile GH plasma profile
      changes, which may also affect expression profiles of genes regulating body
      composition.

PMID- 15451077
TI  - Proceedings of the Third International Meeting of the Society of Hair Testing.
      October 8-10, 2003. Heraklion, Crete.

PMID- 15451078
TI  - Recommendations for hair testing in forensic cases.

PMID- 15451079
TI  - Comparing two analytical methods: minimal standards in forensic toxicology
      derived from information theory.
AB  - Frequently, new instrumentation and techniques are being applied to casework
      without an adequate knowledge of how this new technology compares to acceptable
      analytical procedures. Information theory provides a mathematical method to
      estimate the identification power of various analytical procedures and predicts
      if the new method produces a better or poorer confidence in the analysis than an
      accepted method. This paper makes comparisons based on relative informational
      power and discusses methods to make those estimates. With the procedures outlined
      in this paper, an analyst can estimate if a novel technique has the opportunity
      of reaching the accepted analytical methodology and, if necessary, identify
      places where the greatest improvement can be made to reach this equilivalence.
      Even though relative information theory can dismiss some proposed techniques
      before any analysis starts, it cannot verify if a given technique is adequate for
      a particular task. For that purpose, a complete procedural verification must be
      undertaken.

PMID- 15451080
TI  - Removing and identifying drug contamination in the analysis of human hair.
AB  - The procedure used in this laboratory for removing and identifying contamination
      of hair specimens with drugs is demonstrated by its application to hair
      contaminated by various experimental models. The models include soaking; coating
      with drug followed by sweat conditions for 6 h; and soaking in a very high
      concentration of cocaine followed by storage and multiple shampoo treatments. A
      multi-part wash procedure along with a wash criterion is applied to all samples
      containing drug above the cutoff. The failure of the wash criterion is a signal
      that the sample may be positive due to contamination rather than use, and in the
      absence of other over-riding evidence, the sample would be considered to be
      negative for drug use. This Wash Criterion has also been tested with hair from
      subjects demonstrated to be drug users by one or more drug-positive urines; in
      these studies, all hair samples from demonstrated users passed the Wash Criterion
      test.

PMID- 15451081
TI  - HAIRVEQ: an external quality control scheme for drugs of abuse analysis in hair.
AB  - The Istituto Superiore di Sanita of Rome, Italy, in cooperation with Institut
      Municipal d'Investigacio Medica of Barcelona, Spain, set up an external quality
      control program (HAIRVEQ) to evaluate reliability in hair testing for drug abuse
      by laboratories from the Italian National Health Service. Samples included in the
      program were real hair samples from drugs consumers. Prior to sending, hair
      samples were reduced to powdered form, mixed to ensure homogeneity and tested
      with GC/MS by four Reference Laboratories. Up to now, four different exercises
      have been concluded and 23 laboratories participated. Samples containing high and
      low concentrations of opiates, cocaine and metabolites, low concentrations of
      MDMA and two blank samples, were included in the intercomparison exercises
      performed in the first year of HAIRVEQ activities. Results show an insufficient
      performance of participating laboratories. About 82% of laboratories reported
      incorrect results on a qualitative basis (false positive and false negative
      results) for some of the submitted samples. More than one-half of laboratories
      reported quantitative results (60%). On the basis of the calculated z scores,
      only between 35 and 55% of results reported should be considered as satisfying.
      Guidelines have to be provided by Italian authorities for method validation as
      well as set of recommended cut-off concentrations to orientate laboratories in
      their quality objectives when developing analytical methodologies as tools to
      improve reliability and consequently performance of hair analysis.

PMID- 15451082
TI  - Testing for zopiclone in hair application to drug-facilitated crimes.
AB  - The use of a drug to modify a person's behaviour for criminal gain is not a
      recent phenomenon. However, the recent increase in reports of drug-facilitated
      crimes (sexual assault, robbery) has caused alarm in the general public. The
      drugs involved can be difficult to detect due to low dosages or chemical
      instability. They possess amnesic properties and can be quickly cleared from the
      body fluids. In these situations, blood or even urine can be of poor interest.
      This is the reason why this laboratory developed an original approach based on
      hair testing by LC-MS/MS. Zopiclone (Imovane), due to its short half-life
      associated with rapid hypnotic activity, is considered as a compound of choice to
      sedate victims. To document the detection of zopiclone in hair, we first tested
      specimens obtained from two volunteers who had ingested a single 7.5 mg Imovane
      tablet, and from repetitive consumers of zopiclone. After pH 8.4 buffer
      incubation and extraction with methylene chloride/diethyl ether (80/20 (v/v)),
      hair extracts were separated on a Xterra MS C18 column using a gradient of
      acetonitrile and formate buffer. Zopiclone and diazepam-d5, used as internal
      standard, were detected by tandem mass spectrometry. A single exposure to
      zopiclone was detectable in the first hair segment of two volunteers at
      concentration of 5.4 and 9.0 pg/mg, respectively. Hair from repetitive consumers
      tested positive for zopiclone at concentrations of 37 and 66 pg/mg. Hair analysis
      was applied to two authentic criminal cases. In the first one, zopiclone tested
      positive in the corresponding hair segment at 4.2 pg/mg, in accordance with a
      single exposure to the drug. In the other expertise, zopiclone was detected in
      the two segments analyzed, at 21.3 and 21.5 pg/mg, making unlikely the
      hypothetical single exposure to zopiclone.

PMID- 15451083
TI  - Determination of bromazepam, clonazepam and metabolites after a single intake in
      urine and hair by LC-MS/MS. Application to forensic cases of drug facilitated
      crimes.
AB  - The number of reports on drug facilitated crimes is increasing these last years.
      Apart from ethanol and cannabis, benzodiazepines (BZD) and analogs are the most
      common drugs reported to be used probably due to their amnesic and sedative
      properties. We have developed a rapid and sensitive method using LC-MS/MS triple
      stage quadrupole (TSQ) for the determination of single exposure to bromazepam
      (Lexomil, 6 mg) and clonazepam (Rivotril, 2 mg) in urine and hair of healthy
      volunteers. Chromatography was carried out on a Uptisphere ODB 5 microm, 2.1 mm x
      150 mm column (Interchim) with a gradient of acetonitrile and formate 2 mM
      buffer, pH 3. Urine was extracted with Toxitube A (Varian) and allowed the
      detection of bromazepam, 3-hydroxy-bromazepam, clonazepam and 7-Aminoclonazepam
      for more than 6 days. Head hair, collected 1 month after the exposure, was
      treated by incubation with Soerensen buffer pH 7.6, followed by liquid-liquid
      extraction with dichloromethane for common BZD. A specific pre-treatment for
      amino-BZD, with an incubation of 15 min at 95 degrees C in 0.1 N NaOH before
      liquid-liquid extraction with dichloromethane, gave better recoveries and
      repeatability. After single exposure, bromazepam was present in powdered hair at
      28 pg/mg and 7-Aminoclonazepam at 22 pg/mg in the first 1-cm segment, while no
      clonazepam was detectable. This method was applied in two forensic cases. It
      allowed us to determine bromazepam in urine 3 days after the alleged offense and
      in cut head hair at a concentration of 6.7 pg/mg only in the 2-cm proximal
      segment. The other case showed the presence of clonazepam and 7-Aminoclonazepam
      in urine a few hours after the offense and the presence of 7-Aminoclonazepam at
      about 3.2 pg/mg in axillary hair 4 months later.

PMID- 15451084
TI  - Windows of detection of lorazepam in urine, oral fluid and hair, with a special
      focus on drug-facilitated crimes.
AB  - The purported lowering of sex opposition, coupled with a possible abrupt
      unconsciousness-inducing effect and ease of administration in spiked drinks have
      resulted in the use of hypnotics in cases of drug-facilitated offense. Among
      these compounds, lorazepam possesses amnesic properties and can impair an
      individual rapidly. The chances to detect this substance increase if the most
      sensitive methods are used and if the biological fluid which allows the longest
      possible detection time is available. In order to document the window of
      detection of lorazepam, we have orally administered 2.5 mg of the drug to three
      volunteers and collected oral fluid (n = l) over 8 h, urine (n = 2) over 144 h
      and hair (n = 3) 4 weeks after exposure. Lorazepam was analyzed by LC-MS/MS after
      alkalinisation (to pH 8.4 with phosphate buffer) and extraction by
      dichloromethane/diethyl ether in presence of diazepam-d5, used as internal
      standard. Reversed-phase separation on a XTerra C18 column was achieved in 12
      min, under gradient conditions. Molecular ions (m/z 321 and 290 for lorazepam and
      the IS, respectively) were selected in Ql and the corresponding daughter ions
      (m/z 303 and 275 for lorazepam and m/z 154 and 198 for the IS) were detected in
      Q3 after collision with argon. Urine tested positive for lorazepam over 144 h (2
      4 ng/ml), with a peak detected after 24 h exposure (411-880 ng/ml). Oral fluid
      tested positive for lorazepam over 8 h (0.7 ng/ml). Despite a limit of
      quantitation at 1 pg/mg, we were unable to detect a single lorazepam dose in
      hair, contrarily to most other benzodiazepines that are detectable. Therefore, in
      case of drug-facilitated crimes involving lorazepam, urine appears as the best
      specimen to document exposure, particularly if LC-MS/MS is used.

PMID- 15451085
TI  - Amphetamines in washed hair of demonstrated users and workplace subjects.
AB  - In a study of volunteer subjects from drug rehabilitation programs,
      methamphetamine and amphetamine levels were determined in the hair of 40 subjects
      who had produced MS-confirmed methamphetamine-positive urine results. The samples
      were tested by radioimmunoassay and analyzed by LC/MS/MS after being washed with
      the 3.75-h wash procedure developed by this laboratory. In addition, results of
      non-user and workplace samples are presented. In workplace samples, levels of
      methamphetamine, amphetamine, methylenedioxy-methamphetamine (MDMA), and
      methylenedioxyamphetamine (MDA), are reported. The range of methamphetamine
      levels in the clinical samples (170-34,400 pg/mg hair) was not different from the
      workplace population (from less than the cutoff of 500 pg/mg to >20,000 pg/mg
      hair), but the workplace population had a lower percentage of high levels of
      drug. Amphetamine levels were found to vary widely in both populations, at all
      levels of methamphetamine. In the clinical population, no samples were positive
      for MDMA; in MDMA-positive workplace samples, the levels ranged from below the
      cutoff of 500 to >20,000 pg/mg, with MDA levels varying widely, similar to
      amphetamine levels in methamphetamine-positive samples.

PMID- 15451086
TI  - Cannabinoids in hair: strategy to prove marijuana/hashish consumption.
AB  - Delta9-Tetrahydrocannabinol (THC) and 11-nor-Delta9-tetrahydrocannabinol-9
      carboxylic acid (THCA) are equally used to indicate consumption of cannabis
      (hashish and marijuana). Publications of the early 90's demonstrate the
      possibilities of determining THC, cannabinol (CBN), and cannabidiol (CBD). All
      these substances are present in cannabis smoke and can be incorporated into the
      hair only by contamination. Generally, washing procedures should prevent false
      positive results, but finally it cannot be excluded that traces of THC may be
      found in hair after mere passive cannabis smoke exposure. Three authentic cases
      illustrate the problems originating in the exclusive determination of THC/CBN.
      The first example is the case of a couple living together in an apartment. Both
      persons' hair samples had been taken and gave positive results for THC and CBN.
      The male subject admitted smoking cannabis several times per day, but the female
      mate denied any consumption. Examination of the hair for THCA showed a high level
      (>6.6 pg/mg) in the sample of the male person and negative results (LOQ 0.1
      pg/mg) in the sample of his mate. The second case hair is of a self admitted
      cannabis user's hair and was tested first by an immunoassay and GC/MS with a
      negative result. Nevertheless, the THCA concentration quantified in his sample
      was 2.7 pg/mg hair. The third hair sample is of a 2-year-old child that was
      tested positive for cannabis by using an immunochemical test. No THC and CBN were
      detectable by GC/MS, however, trace amounts of THCA using GC/MS/MS. A comparative
      study of hair samples (screening for cannabinoids using ELISA test, THC
      determination by GC/MS, THCA by GC/MS/MS) showed that only 26 segments of 66 were
      positive for both THC and THCA. Thirteen were negative for THC and positive for
      THCA, and six were positive for THC but negative for THCA. The cases were
      selected by an ELISA test or re-examined when the blood/urine results or the
      statement of the accused did not match with a THC outcome. The most appropriate
      strategy to prove cannabis consumption is immunochemical initial test followed by
      a GC/MS/MS confirmation of THCA.

PMID- 15451087
TI  - Squalene in hair--a natural reference substance for the improved interpretation
      of fatty acid ethyl ester concentrations with respect to alcohol misuse.
AB  - Fatty acid ethyl esters (FAEE) are incorporated into hair mainly from sebum. For
      this reason, the use of their concentration CFAEE as marker of excessive alcohol
      consumption is complicated by interindividual differences of the activity of the
      sebum glands and of elimination by hair care and hair cosmetics. Furthermore, an
      influence of the investigated hair length due to increasing accumulation from
      proximal to distal was found. Therefore, it was examined whether these sources of
      error can be avoided if in addition to CFAEE the relative FAEE concentrations
      CFAEE/CSQ related to squalene SQ as a natural reference compound were used for
      interpretation. Sebum contains about 10-20% SQ. A sensitive and reliable method
      for the determination of SQ in addition to FAEE from the same hair extracts by
      high performance liquid chromatography with photo diode array detector (HPLC-DAD)
      was developed. The concentrations of ethyl myristate, ethyl palmitate, ethyl
      oleate, ethyl stearate and squalene were determined and CFAEE/CSQ was calculated
      for 13 teetotallers, 16 social drinkers, 12 fatalities with excessive alcohol
      abuse at life time and 9 cases with unclear alcohol anamnesis. CSQ ranged from
      0.02 to 1.97 microg/mg (mean 0.67 microg/mg). From the results follows that
      squalene enables a control of the lipid content of hair and a correction of CFAEE
      in cases with deviations from the usual lipid content in a similar way as
      creatinine in urine. Preliminary values of CFAEE/CSQ were suggested for the upper
      limit for teetotallers (< 0.6 ng/microg) and the lower limit for excessive
      alcohol abuse (> 1.5 ng/microg). However, the relative concentration CFAEE/CSQ
      cannot completely replace the absolute concentration CFAEE, and both should
      regularly be used for an improved interpretation with respect to alcohol abuse.

PMID- 15451088
TI  - Diagnosis of chronic alcohol consumption. Hair analysis for ethyl-glucuronide.
AB  - This paper describes a procedure for the detection and quantification of ethyl
      glucuronide (EtG) in hair samples. During method development the efficacy of
      extraction of EtG from hair was compared in four extraction methods: (a)
      methanol; (b) methanol:water (1:1); (c) water; and (d) water:trifluoroacetic acid
      (9:1). In addition, three derivatizing agents were compared as well: N,O
      bistrimethylsilyl-trifluoroacetamide (BSTFA): trimethylchlorosilane (TMCS)
      (99:1), pentafluoropropionic anhydride (PFPA) and heptafluorobutyric anhydride
      (HFBA). Water was found to be the best extracting solvent and PFPA the best
      derivatizing agent. Both provided the highest recoveries, with cleaner extracts
      and more stable derivatives. The final method is as follows: about 100mg of hair
      are sequentially washed with water and acetone. The decontaminated sample is
      finely cut with scissors, then the deuterated internal standard (EtG-d5) and 2 mL
      of water are added. After sonication for 2 h, the sample is maintained at room
      temperature overnight. Derivatization is performed with PFPA. Derivatives are
      injected into a GC-MS system in the electronic impact mode. The method shows
      linearity over the range of concentrations from 0.050 to 5 ng/mg. Detection and
      quantification limits are 0.025 and 0.050 ng/mg, respectively. Mean recoveries
      for the three studied concentrations (low, medium and high) are higher than 87%.
      The coefficients of variation in intra- and inter-assay precision are always
      lower than 7%. The method is being routinely applied in our lab for the diagnosis
      of chronic alcohol consumption.

PMID- 15451089
TI  - Comparison of ethyl glucuronide and fatty acid ethyl ester concentrations in hair
      of alcoholics, social drinkers and teetotallers.
AB  - In previous investigations hair analysis for ethyl glucuronide (EtG) and fatty
      acid ethyl esters (FAEE) proved to be suitable for the detection of excessive
      alcohol consumption. The aim of this study was to compare EtG and FAEE
      concentrations in hair of alcoholics, social drinkers and teetotallers. Hair
      samples from 10 alcoholics in withdrawal treatment, 11 fatalities with documented
      excessive alcohol consumption, four moderate social drinkers who consumed up to
      20 g ethanol per day, and three strict teetotallers were analysed. After external
      degreasing with n-heptane, extraction with a dimethyl sulfoxide/n-heptane mixture
      and headspace solid-phase microextraction of the extracts, four fatty acid ethyl
      esters (FAEEs) (ethyl myristate, ethyl palmitate, ethyl oleate and ethyl
      stearate) were analysed by gas chromatography-mass spectrometry (GC-MS) with
      deuterated internal standards. EtG was determined by GC-MS/NCI after
      ultrasonication of the samples with H2O, cleanup by SPE with aminopropyl columns
      and PFP derivatisation. The following concentrations were measured for the four
      groups: teetotallers EtG < 0.002 ng/mg, FAEE 0.05-0.37 ng/mg, moderate social
      drinkers EtG < 0.002 ng/mg, FAEE 0.26-0.50 ng/mg, alcoholic patients EtG 0.030
      0.415 ng/mg, FAEE 0.65-20.50 ng/mg and the fatalities with alcohol history EtG
      0.072-3.380 ng/mg, FAEE 1.30-30.60 ng/mg. The results confirm that by using a cut
      off value of the sum of FAEE > 1 ng/mg and/or a positive EtG result in hair,
      excessive alcohol consumption can be identified using hair analysis. However, no
      significant correlation between the EtG and FAEE concentrations in the positive
      cases could be shown. Segmental analysis of some of the specimens did not reveal
      the same distribution for EtG compared to FAEE in hair, and no chronological
      accordance compared to the self-reported alcohol consumption could be observed
      for both parameters. These different results of both methods are discussed in
      terms of differences between EtG and FAEE in mechanism of formation and
      incorporation into hair and elimination from hair.

PMID- 15451090
TI  - Levels of cocaine and its metabolites in washed hair of demonstrated cocaine
      users and workplace subjects.
AB  - In a study of subjects in drug rehabilitation programs, cocaine and cocaine
      metabolite levels were determined in the hair of 75 subjects who had produced
      cocaine-positive urine results. The hair was analyzed after being washed with the
      3.75 h wash procedure developed by this laboratory. In addition, results of
      testing 73 non-users are presented, as well as levels of cocaine, benzoylecgonine
      (BE), cocaethylene, and norcocaine from workplace population samples. The data
      support a recommendation of reporting as positive a sample with cocaine of 500
      pg/mg hair and either a 5% ratio of benzoylecgonine (BE) to cocaine in samples,
      or the presence of cocaethylene at 50 pg/mg hair, or norcocaine at 50 pg/mg hair
      for samples < or =2000 pg cocaine/mg hair. For samples with cocaine present at
      >2000 pg/mg hair, the data indicate that a ratio of 5% BE may be an overly
      conservative approach. In appropriately washed hair samples, cocaine users can
      produce hair levels of <5% BE and thus a minimum BE cutoff in lieu of a ratio
      could be considered.

PMID- 15451091
TI  - Screening for drugs of abuse in hair with ion spray LC-MS-MS.
AB  - Analyzing hair for many substances can be tedious and expensive, and a rapid
      screening method should prove helpful. Generally, screening has been performed
      using immunological tests, mainly in workplace drug testing, where the number of
      samples has been high. The aim of this study was to develop an LC-MS-MS method
      for the simultaneous analysis of several drugs of abuse in human hair as an
      alternative to immunological screening tests. In 75 randomly selected autopsy
      cases, hair was analyzed in addition to the usual specimens of blood and urine.
      The method included nicotine, cotinine, morphine, codeine, 6-acetylmorphine,
      ethylmorphine, amphetamine, methamphetamine, MDA, MDMA, benzoylecgonine, cocaine,
      7-aminoflunitrazepam and diazepam. The LC-MS-MS analysis was performed on a SCIEX
      API 2000 MS-MS instrument equipped with an electrospray interface. To 20-50 mg of
      hair, 0.5 ml of mobile phase A (acetonitril:methanol:20 mM formate buffer, pH 3.0
      (10:10:80)) and 25 microl of internal standard were added and the sample was
      incubated in a water bath at 37 degrees C during 18 h. Using a threshold of 20
      ng/sample, equivalent to 1 ng/mg if 20mg hair is used, 26 positive results were
      found in 16 cases. Three of the 26 positive detections could not be confirmed by
      GC-MS. Two of the cases were not previously known as drug users. Of the 59
      negative cases, only one case had a positive blood sample showing 0.01 and 0.07
      microg/g femoral blood of 6-acetylmorphine and morphine, respectively. This might
      indicate drug abstinence resulting in decreased tolerance or even a "first time"
      use of heroin resulting in death. We conclude that the use of hair analysis in
      postmortem cases can reveal both unknown drug use, as well as confirm a period of
      drug abstinence prior to an acute fatal overdose. The proposed LC-MS-MS method
      showed high sensitivity, was very easy to perform and seemed appropriate for
      screening purposes.

PMID- 15451092
TI  - Assessing nicotine metabolism in pregnancy--a novel approach using hair analysis.
AB  - Nicotine and its metabolite cotinine are important biochemical markers to
      determine active or passive exposure to cigarette smoke. The amount of nicotine
      and cotinine in hair provides a cumulative index of tobacco exposure. This study
      uses segmental hair analysis to assess changes in nicotine metabolism in a cohort
      of pregnant women who smoked steadily during the whole gestational period
      according to their self-report. Maternal hair was collected at the time of
      delivery and sectioned into segments representing the three trimesters of
      pregnancy. The concentrations of nicotine and cotinine in each section of hair
      were measured by radioimmunoassay. Hair concentration of nicotine decreased
      during pregnancy without any reported reduction in smoking, while the cotinine
      concentration remained constant. The nicotine-cotinine ratio in these consistent
      smokers was: 1st trimester 20.6, 2nd trimester 19.9, and 3rd trimester 13.3.
      These findings are consistent with results from other studies showing increased
      nicotine metabolism during pregnancy. Our data suggest that the results of
      segmental hair analysis should be carefully examined in pregnancy. Both nicotine
      and cotinine levels should be evaluated in order to confirm any significant
      change in maternal tobacco exposure during pregnancy.

PMID- 15451093
TI  - Progress in pesticide and POPs hair analysis for the assessment of exposure.
AB  - The present paper reviews the work that has been done in the field of pesticide
      and persistent organic pollutants (POPs) hair analysis during the last 15 years.
      It summarizes the compounds of interest, the methods of analyte extraction from
      the hair matrix, the analytical techniques employed and the results obtained. The
      most widely studied POPs are the polychlorinated dibenzodioxins (PCDDs), the
      dibenzofurans (PCDFs) the co-planar biphenyls (co-PCBs) and total biphenyls
      (PCBs). The most widely studied pesticides are the organochlorine ones, like the
      hexachlorocyclohexanes and the DDTs, which nowadays are only found as
      environmental pollutants, some organophosphates, selected pyrethroids and the
      carbamate methomyl. The most widely applied technique was gas chromatography (GC)
      coupled to mass spectrometry (MS). Other detectors like the ECD in the case of
      organochlorine analysis and the NPD in the case of organophosphate analysis were
      also used. The presented data concern human and animal studies. The levels of
      DDTs detected in hair were between 19 and 400 ng/g, of co-PCBs 0.27 and 0.45
      ng/g, of total PCBs 5-13 ng/g of PCDDs and PCDFs 0.1-10 pg/g of lindane 20-400
      ng/g of HCHs 14-40 ng/g of diazinon 110-520 ng/g and of methomyl 900-1800 ng/g.
      These results strongly support the possibility of using hair as a suitable
      indicator for the assessment of long-term exposure to POPs and pesticides.

PMID- 15451094
TI  - Chemotaxis in Vibrio cholerae.
AB  - The ability of motile bacteria to swim toward or away from specific environmental
      stimuli, such as nutrients, oxygen, or light provides cells with a survival
      advantage, especially under nutrient-limiting conditions. This behavior, called
      chemotaxis, is mediated by the bacteria changing direction by briefly reversing
      the direction of rotation of the flagellar motors. A sophisticated signal
      transduction system, consisting of signal transducer proteins, a histidine
      kinase, a response regulator, a coupling protein, and enzymes that mediate
      sensory adaptation, relates the input signal to the flagellar motor. Chemotaxis
      has been extensively studied in bacteria such as Escherichia coli and Salmonella
      enterica serovar Typhimurium, and depends on the activity of single copies of
      proteins in a linear pathway. However, growing evidence suggests that chemotaxis
      in other bacteria is more complex with many bacterial species having multiple
      paralogues of the various chemotaxis genes found in E. coli and, in most cases,
      the detailed functions of these potentially redundant genes have not been
      elucidated. Although the completed genome of Vibrio cholerae, the causative agent
      of cholera, predicted a multitude of genes with homology to known chemotaxis
      related genes, little is known about their relative contribution to chemotaxis or
      other cellular functions. Furthermore, the role of chemotaxis during the
      environmental or infectious phases of this organism is not yet fully understood.
      This review will focus on the complex relationship between chemotaxis and
      virulence in V. cholerae.

PMID- 15451095
TI  - Functional importance of Asp37 from a family 11 xylanase in the binding to two
      proteinaceous xylanase inhibitors from wheat.
AB  - Aspergillus niger xylanase is a target enzyme of the two wheat proteinaceous
      inhibitors, XIP-I and TAXI-I. We previously suggested that the xylanase "thumb"
      region was XIP-I binding site. Here, we expressed the Asp37Ala mutant in Pichia
      pastoris and showed that the mutation abolished the enzyme capacity to interact
      with both inhibitors, suggesting a direct contact at the active site. The mutant
      pH profile was altered, confirming the key role of Asp37 in determining the pH
      optima of glycoside hydrolase family 11. The results are consistent with a
      competitive inhibition mode and underline the strategic importance of Asp37 in
      the inhibition mechanism.

PMID- 15451096
TI  - Intragenomic heterogeneity of the 16S rRNA-23S rRNA internal transcribed spacer
      among Pseudomonas syringae and Pseudomonas fluorescens strains.
AB  - The 16S-23S rRNA internal transcribed spacer regions (ITS1) from 14 strains of
      Pseudomonas syringae and P. fluorescens were sequenced. ITS1 exhibited
      significant sequence variability among different operons within a single genome.
      From 1 to 4 types of ITS1 were found in individual genomes of the P. syringae and
      P. fluorescens strains. A total of eight ITS1 types were identified among strains
      studied. The ITS1 nucleotide sequences consisted of conserved blocks including,
      among others, a stem-forming region of box B, tRNAIle and tRNAAla genes and
      several variable blocks. The differences in the variable regions were mostly due
      to insertions and/or deletions of nucleotide blocks. The intragenomic
      heterogeneity of ITS1 was brought about by different combinations of variable
      blocks, which possibly have resulted from recombination and horizontal transfer.

PMID- 15451097
TI  - Analysis of integrons in human isolates of Salmonella enterica serovar
      typhimurium isolated in the Slovak Republic.
AB  - About 110 sporadic, epidemiologically unrelated Salmonella enterica serovar
      typhimurium strains isolated in the Slovak Republic were analyzed for the
      presence of integrons. Of these 110 examined strains, 47 were of definitive phage
      type DT104 and 63 were strains of various phage type, RDNC and untypeable,
      designated here as non-DT104 strains. All isolates were also tested for
      antimicrobial resistance to 10 antibiotics as well as for the presence of
      virulence plasmid. Of 63 non-DT104 strains, 15 isolates were multiple-resistant,
      independently from phage type, other strains were resistant to one, two or three
      drugs. Resistance to ampicillin, streptomycin, tetracycline and sulfisoxazole was
      most frequently observed. Among the DT104 isolates up 65.9% exhibited
      characteristic pentaresistance--ACSSuT phenotype. The integron content was
      studied in PCR experiments using a 5'-CS/3'-CS primer pair. Fourteen non-DT104
      strains, independently from phage type, were found to carry integrons with
      amplicons 650-1900 bp in size. Thirty-six DT104 strains contained integrons of
      1000 and 1200 bp and 31 of they exhibited the ACSSuT phenotype. No integron was
      found in 10 DT104 strains, which included strains mostly resistant only to
      streptomycin, tetracycline and sulfisoxazole. The majority of non-DT104 strains
      did not possess any integrons. Our findings show the widespread existence of both
      resistant and multiple-resistant epidemiologically unrelated Salmonella
      typhimurium strains and suggest that integrons contribute to this antimicrobial
      resistance. The presence of 90-kb virulence plasmid in the 54 non-DT104 and in
      the all DT104 strains was found.

PMID- 15451098
TI  - Expression and purification of recombinant methylated HBHA in Mycobacterium
      smegmatis.
AB  - The Heparin-Binding Haemagglutinin (HBHA) is a mycobacterial adhesin involved in
      the dissemination of Mycobacterium tuberculosis from the site of primary
      infection and a potential candidate for the development of a new vaccine against
      tuberculosis. Methylation of HBHA is a novel post-translational event that
      imparts important immunological properties to the protein. Since recombinant HBHA
      expressed in Escherichia coli is not methylated, we investigated the possibility
      of producing recombinant methylated HBHA in fast growing mycobacteria for use in
      immunological and biochemical studies. The complete coding sequence of HBHA was
      cloned in the plasmid pMV206, under the control of a strong promoter (hsp60) or
      its own promoter. The constructs generated were electroporated into Mycobacterium
      smegmatis and the recombinant strains obtained were analyzed for the presence of
      the HBHA protein using the anti-HBHA monoclonal antibodies D2 and E4. Our results
      indicate that expression of high amounts of intact protein can be toxic for the
      mycobacteria, that methylated HBHA can be obtained in M. smegmatis only when
      using a promoter sequence weaker than hsp60 and that the expression of the
      complete structural gene is required in order to obtain methylated HBHA. We
      constructed a recombinant M. smegmatis strain (pMV3-38) that expresses a
      histidine-tagged methylated HBHA that can be easily purified. The use of fast
      growing strains of M. smegmatis to obtain significant amounts of purified HBHA
      protein within a short timeframe, should be an effective strategy for the
      evaluation of a new HBHA-based vaccine candidate for tuberculosis.

PMID- 15451099
TI  - Identification of Mycobacterium avium genes up-regulated in cultured macrophages
      and in mice.
AB  - To investigate Mycobacterium avium gene expression upon infection of macrophages,
      we created a M. avium-promoter library upstream of a promoter-less gene encoding
      the green fluorescent protein (GFP) in Mycobacterium smegmatis. Clones were
      evaluated for increased expression of GFP after infection of U937 macrophages. A
      number of M. avium genes were up-regulated more than 3-fold after 24 and 48 h
      following macrophage infection. M. avium genes expressed by M. smegmatis during
      growth in macrophages include genes encoding transport/binding proteins,
      synthesis, modification and degradation of macromolecules, and a great majority
      of genes for which no function is currently known. For some of the unknown genes,
      homologues were identified in bacteria such as Mycobacterium leprae, Salmonella
      typhimurium and Agrobacterium tumefaciens. In order to investigate if these genes
      were also expressed in M. avium during macrophage infection in vitro and in vivo,
      transcripts of selected genes were quantified using real time RT-PCR. Evaluation
      of most expressed genes in M. smegmatis confirmed their up-regulation in M. avium
      after 24 h infection of macrophages in vitro and mice.

PMID- 15451100
TI  - Water table related variations in the abundance of intact archaeal membrane
      lipids in a Swedish peat bog.
AB  - The presence and distribution of isoprenoid glycerol dialkyl glycerol tetraethers
      (GDGTs), lipids that constitute the membranes of Archaea, have been investigated
      in a 50-cm long core from a Swedish peat bog. In the acrotelm, the periodically
      water saturated and thus oxic upper layer of the peat bog, only minor amounts of
      GDGTs were found. These amounts increase considerably in the catotelm, the
      continuously water saturated and consequently anoxic lower layer of the peat bog.
      Based on earlier analyses of GDGTs in different settings and on 16S rDNA results
      from literature, these lipids are likely derived from methanogenic Archaea.
      Crenarchaeol, previously only found in marine settings and in fresh water lakes,
      has also been found in this peat bog. Contrary to the other GDGTs, crenarchaeol
      concentrations remain relatively constant throughout the peat core, suggesting
      that they are produced by Crenarchaeota thriving in the oxic part of the peat bog
      and possibly also in the anoxic part.

PMID- 15451101
TI  - Cloning and developmental expression of a metzincin family metalloprotease cDNA
      from oyster mushroom Pleurotus ostreatus.
AB  - A cDNA clone, PoMTP, encoding a putative metzincin family metalloprotease was
      isolated from the expressed sequence tags of a basidiomycete Pleurotus ostreatus.
      The 5'-end sequence of PoMTP was determined by the 5'-RACE method. Full-length
      cDNA sequence (1140 bp) of PoMTP contained a 870 bp open reading frame encoding a
      protein product of 290 amino acids in addition to a 99 bp of 5'-untranslated
      sequence and a 171 bp of 3'-untranslated sequence with a poly(A) tail. The
      deduced amino-acid sequences of PoMTP contained an extensive zinc-binding
      consensus sequence and a so-called Met-turn sequence which are typical for the
      metzincin family of metalloproteases, indicating that the PoMTP protein belongs
      to the metzincin metalloproteases. Four cysteine residues were also observed in
      the zinc-binding region of PoMTP amino-acid sequence, which are known to be
      important for the structure and the function of some subfamilies of the
      metzincins. Comparison of the PoMTP in sequence database showed no significant
      homology with functionally known metalloproteases of Armillaria mellea, Grifola
      frondosa, Lentinula edodes, Pleurotus ostreatus, Schizophyllum commune and
      Tricholoma saponaceum in mushroom. Northern blot and qunatitative RT-PCR analyses
      indicated the PoMTP mRNA to be abundant at primordial and fruit body stages, but
      scarce at the mycelial stage, suggesting that the PoMTP metalloprotease plays an
      important role in mushroom fruiting.

PMID- 15451102
TI  - Influence of environmental conditions on the expression of virulence factors by
      Listeria monocytogenes and their use in species identification.
AB  - The hemolytic, lecithinase or phosphatidylinositol-specific phospholipase C
      activities of Listeria monocytogenes can be used to differentiate this pathogenic
      bacteria from L. innocua, apathogenic, frequently isolated from environmental
      sources and food. However, the interpretation of these characteristics is
      problematic because of the variation in the expression of virulence factors by L.
      monocytogenes, which can be influenced by environmental conditions. We used a
      cheap, simple plate assay to monitor this expression in strains obtained from
      various sources and grown under different culture conditions. The results were
      increasingly significant and were obtained adding activated charcoal and
      different salts to the culture media, and in some cases changing the culture
      temperature, all with a rigorous control on the process of media sterilization.

PMID- 15451103
TI  - Analysis of the germination of spores of Bacillus subtilis with temperature
      sensitive spo mutations in the spoVA operon.
AB  - A Bacillus subtilis strain with a base substitution in the ribosome-binding site
      of spoVAC was temperature sensitive (ts) in sporulation and spores prepared at
      the permissive temperature were ts in L-alanine-triggered germination, but not in
      germination with Ca2+-dipicolinic acid (DPA) or dodecylamine. Spores of a ts spo
      mutant with a missense mutation in the spoVAC coding region were not ts for
      germination with l-alanine, dodecylamine or Ca2+-DPA. These findings are
      discussed in light of the proposal that SpoVA proteins are involved not only in
      DPA uptake during sporulation, but also in DPA release during nutrient-mediated
      spore germination.

PMID- 15451104
TI  - Development of a novel quadruple auxotrophic host transformation system by argB
      gene disruption using adeA gene and exploiting adenine auxotrophy in Aspergillus
      oryzae.
AB  - We previously designed a triple auxotrophic host-vector system in Aspergillus
      oryzae by isolating red-colored adenine auxotrophic mutants upon UV mutagenesis
      of a double auxotrophic host (niaD-sC-). In the present study an effort to
      exploit this system and construct a novel quadruple auxotrophic host was made by
      disrupting the argB gene involved in arginine biosynthesis. The argB gene
      disruption cassette was generated by fusion PCR, which required only two steps of
      PCR to insert the selectable marker, adeA, into the target argB gene. The
      chimeric DNA fragment was transformed into the triple auxotrophic strain (niaD-sC
      adeA-) and the argB disruptants were obtained with a high rate of efficiency
      (approximately 40%). The argB disruptants were characterized by normal colony
      color and reversal of arginine auxotrophy by introduction of the wild-type argB
      gene. Quadruple auxotrophic strains (niaD-sC-DeltaargB adeA- or niaD-sC-DeltaargB
      adeB-) were subsequently isolated upon UV mutagenesis of the triple auxotrophic
      strain (niaD-sC-DeltaargB) followed by screening of red-colored colonies for
      adenine auxotrophy. The results obtained showed that the adeA gene served as an
      efficient selection marker in developing a novel host-vector system with
      quadruple auxotrophy in A. oryzae, thus providing a powerful tool to breed
      multiple auxotrophic mutants from a deuteromycete wherein sexual crossing is
      impossible.

PMID- 15451105
TI  - Characterisation and expression of phospholipases B from the opportunistic fungus
      Aspergillus fumigatus.
AB  - The phospholipase B family (PLB) are enzymes sharing phospholipase (PL),
      lysophospholipase (LPL) and lysophospholipase-transacylase (LPTA) activities.
      They have been shown to be important virulence factors in several human fungal
      pathogens including Candida albicans and Cryptococcus neoformans. Aspergillus
      fumigatus, a human opportunistic fungal pathogen leading to a high rate of
      mortality in immunosuppressed patients is known to possess an extracellular
      phospholipase B activity. In this paper, we report the molecular characterisation
      of three PLB genes from A. fumigatus (afplb) using degenerate primers in PCR
      amplification and data from the A. fumigatus genome project. They are expressed
      at 37 degrees C, and two of them (afplb1 and afplb3) are induced by lecithin.
      They encode proteins of 633, 588 and 630 amino acids, respectively, presenting
      together a T-Coffee score of 81. They also possess the amino acid triad
      responsible for enzymatic activity in the mammalian cytosolic PLA2 and other
      fungal PLBs. AfPLB1 and afPLB3 are secreted with a cleaved signal peptide. The
      complete cDNA sequences were obtained by RACE-PCR for the two secreted afPLBs and
      probably account for the extracellular phospholipase activity previously reported
      in the culture media of A. fumigatus.

PMID- 15451106
TI  - Glutamic protease distribution is limited to filamentous fungi.
AB  - Glutamic proteases are a distinct, and recently re-classified, group of
      peptidases that are thought to be found only in fungi. We have identified and
      analysed the distribution of over 20 putative glutamic proteases from all fungal
      species whose genomes have been sequenced so far. Although absent from the
      Saccharomycetales class, glutamic proteases appear to be present in all other
      ascomycetes species examined. A large number of coding regions for glutamic
      proteases were also found clustered together in the Phanerochaete chrysosporium
      genome, despite apparently being absent from three other species of
      Basidiomycota.

PMID- 15451107
TI  - Isolation and characterisation of an isoproturon-mineralising Methylopila sp. TES
      from French agricultural soil.
AB  - Using enrichment culture three isoproturon (IPU) mineralising bacterial isolates
      were isolated from a French agricultural soil mineralising up to 50% of the
      initially added 14C-ring labelled IPU within only eight days. These isolates
      showed similar metabolic (BIOLOG GN) and amplified rDNA restriction (ARDRA)
      profiles. Partial 16S rDNA sequencing revealed that they were identical and
      identified as Methylopila sp TES. This strain harbours a large plasmid (220 kb)
      putatively bearing essential IPU-degrading genes as demonstrated by a curing
      experiment. Methylopila sp. TES transformed IPU and its known metabolites to CO2
      and biomass but did not degrade chlorotoluron, monolinuron, diuron and linuron.

PMID- 15451108
TI  - Evaluation of the robustness of FT-IR spectra of lactobacilli towards changes in
      the bacterial growth conditions.
AB  - In order to use Fourier Transform Infrared (FT-IR) spectroscopy for
      identification of microorganisms on a routine basis, it is important that the
      spectra are robust against small, uncontrollable variations in the bacterial
      growth conditions. In this study, the effect of small variations in growth
      temperature, growth time, growth medium and atmospheric conditions on the
      separation of Lactobacillus based on their FT-IR spectra was investigated. The
      resulting spectra were shown to be robust against the variations in the
      cultivation conditions, and the separation of both strains and species was
      unaffected. Larger variations in the growth medium influenced only the separation
      of strains. FT-IR spectroscopy for identification of lactobacilli therefore seems
      to be robust against small variations in the cultivation conditions.

PMID- 15451109
TI  - Abundance of 4Fe-4S motifs in the genomes of methanogens and other prokaryotes.
AB  - The abundance of 4Fe-4S motifs of the form CX2CX2CX3C was analyzed in the open
      reading frames (ORFs) of 120 prokaryotic genomes. The abundance of ORFs
      containing the CX2CX2CX3C motif or isORFs correlated (r=0.82) with methanogenesis
      (p=0.0001), archaea (p=0.0173), anaerobiosis (p<0.0001) and genome size
      (p<0.0001). Optimal growth temperature (hyperthermophily) did not correlate with
      the number of isORFs (p=0.6283). Large numbers of CX2CX2CX3C motifs may be
      associated with unique physiologies: methanogenic archaea contained the greatest
      number of CX2CX2CX3C motifs found among the prokaryotic groups; however, only
      about 15% of the motifs were in genes directly involved in methanogenesis. Large
      numbers of CX2CX2CX3C motifs may also be associated with generalists such as
      Desulfitobacterium hafniense, which is an anaerobic bacterium containing multiple
      reductases.

PMID- 15451110
TI  - Isolation and characterization of a cytotoxin produced by Plesiomonas
      shigelloides P-1 strain.
AB  - In order to clarify the enteropathogenicity of Plesiomonas shigelloides, we
      investigated a cytotoxin produced by the P-1 strain isolated from patients
      suffering from diarrhea. The cytotoxicity of the culture filtrate of the strain
      reached a maximum in culture at 37 degrees C after 12 h shaken in BHI medium. The
      cytotoxin in the cultures was purified by (NH4)2SO4 precipitation, and Sephacryl
      S-100, Mono Q HR, and Superdex 200 HR column chromatographies. An approximate 340
      fold purification was achieved, with a recovery of about 1.4%, from the culture
      supernatant. The cytotoxin is heat-stable, and is a complex of three major
      proteins (LPS-binding proteins with molecular weights of 32, 40, and 48 kDa),
      with lipopolysaccharide (LPS) giving a total a molecular weight of more than 600
      kDa. The ratio of protein to LPS in the cytotoxin was 6-5. The cytotoxic activity
      was reduced by about 80% by proteinase K treatment or when incubated with anti
      cholera toxin antibody (Anti-CT). Western blotting of the cytotoxin with Anti-CT
      demonstrated the presence of two anti-cholera toxin-reactive protein (ACRP) bands
      with molecular weights of 40 kDa (a major single protein band) and 48 kDa. The N
      terminal amino acid sequence (20 residues) of the 40 kDa protein was 75%
      identical to Pasteurella multocida cell membrane proteins. The cytotoxin gave a
      positive reaction in the suckling mouse assay whereas LPS alone hardly exhibited
      any cytotoxic or enterotoxigenic activity. In conclusion, P. shigelloides
      produces a cytotoxin that consists of a complex of protein and LPS with the
      former component exhibiting both cytotoxicity and enteropathogenicity. This
      cytotoxin has the potential to have an important role in the enteropathogenicity
      of P. shigelloides.

PMID- 15451111
TI  - Identification and molecular characterization of the gene encoding coli surface
      antigen 20 of enterotoxigenic Escherichia coli.
AB  - Enterotoxigenic Escherichia coli (ETEC) is a major cause of diarrhea among
      children living in developing countries and of travelers' diarrhea. Current ETEC
      vaccine designs aim to induce an anti-colonizing immunity by including the ETEC
      surface colonization factor antigens. We isolated and characterized the
      structural gene of the coli surface antigen 20 (CS20). CS20 has an N-terminal
      amino acid sequence similar to that of CS18. We therefore used a DNA fragment
      carrying the CS18 fotA gene as a probe in a hybridization assay to detect the
      corresponding gene in a CS20-positive strain isolated from an Indian child. Cross
      hybridizing DNA was isolated and found to contain an open reading frame encoding
      a polypeptide of 195 amino acids, including a 22 amino acid signal peptide. The
      gene, which we named csnA, shows a high degree of identity to the major fimbrial
      subunits of CS12, CS18 and F6 (also referred to as 987P), a CS of porcine ETEC.
      The coding region of csnA was inserted into an expression system to generate a
      polypeptide confirmed to be CS20 by Western blot. A CS20 colony hybridization
      assay using a DNA probe derived from csnA was developed.

PMID- 15451112
TI  - Salt-tolerance genes involved in cation efflux and osmoregulation of
      Sinorhizobium fredii RT19 detected by isolation and characterization of Tn5
      mutants.
AB  - Salt-tolerance genes of Sinorhizobium fredii RT19 were identified by the
      construction and screening of a transposon Tn5-1063 library containing over
      30,000 clones. Twenty-one salt-sensitive mutants were obtained and five different
      genes were identified by sequencing. Eight mutants were found with disruptions in
      the phaA2 gene, which encodes a cation efflux system protein, while mutations in
      genes encoding other cation effux system proteins were found in seven (phaD2),
      two (phaF2) and two (phaG2) mutants. A mutation in the metH gene, encoding 5'
      methyltetrahydrofolate homocysteine methyltransferase, was found in two of the
      salt sensitive strains. Growth experiments showed that phaA2, phaD2, phaF2 and
      phaG2 mutants were hypersensitive to Na+/Li+ and slightly sensitive to K+ and not
      sensitive to sucrose and that metH mutants were highly sensitive to any of Na+,
      Li+, K+ and sucrose. Na+ intracellular content measurements established that
      phaA2, phaD2, phaF2 and phaG2 are mainly involved in the Na+ efflux in S. fredii
      RT19. Recovery of growth of the metH mutants incubated with different
      concentrations of NaCl could be obtained by additions of methionine, choline and
      betaine, which showed that the metH gene is probably involved in osmoregulation
      in S. fredii RT19.

PMID- 15451113
TI  - Genetic characterization of the dibenzofuran-degrading Actinobacteria carrying
      the dbfA1A2 gene homologues isolated from activated sludge.
AB  - Thirteen dibenzofuran (DF)-utilizing bacteria carrying the DF terminal
      dioxygenase genes homologous to those of Terrabacter sp. strain DBF63 (dbfA1A2)
      were newly isolated from activated sludge samples. The amplified ribosomal DNA
      restriction analysis and the hybridization analyses showed that these strains
      were grouped into five genetically different types of bacteria. The sequence
      analyses of the 16S rRNA genes and the dbfA1A2 homologues from these five
      selected isolates revealed that the isolates belonged to the genus Rhodococcus,
      Terrabacter or Janibacter and that they shared 99-100% conserved dbfA1A2
      homologues. We investigated the genetic organizations flanking the dbfA1A2
      homologues and showed that the minimal conserved DNA region present in all five
      selected isolates consisted of an approximately 9.0-kb region and that their
      outer regions became abruptly non-homologous. Among them, Rhodococcus sp. strain
      DFA3 possessed not only the 9.0-kb region but also the 6.2-kb region containing
      dbfA1A2 homologues. Sequencing of their border regions suggested that some
      genetic rearrangement might have occurred with insertion sequence-like elements.
      Also, within their conserved regions, some insertions or deletions were observed.

PMID- 15451114
TI  - Resistance of Gram-positive bacteria to nisin is not determined by lipid II
      levels.
AB  - Lipid II is essential for nisin-mediated pore formation at nano-molar
      concentrations. We tested whether nisin resistance could result from different
      Lipid II levels, by comparing the maximal Lipid II pool in Micrococcus flavus
      (sensitive) and Listeria monocytogenes (relatively insensitive) and their nisin
      resistant variants, with a newly developed method. No correlation was observed
      between the maximal Lipid II pool and nisin sensitivity, as was further
      corroborated by using spheroplasts of nisin-resistant and wild-type strains of M.
      flavus, which were equally sensitive to nisin.

PMID- 15451115
TI  - The Aspergillus niger annexin, anxC3.1 is constitutively expressed and is not
      essential for protein secretion.
AB  - An annexin, anxC3.1, was isolated and characterised from the industrially
      important filamentous fungus Aspergillus niger. anxC3.1 is a single copy gene
      encoding a 506 amino acid predicted protein which contains four annexin repeats.
      Disruption of the anxC3.1 gene did not lead to any visible changes in phenotype,
      nor in the levels of secreted protein, nor specifically in glucoamylase
      production, suggesting no major role in secretion. anxC3.1 expression was found
      to be unaltered under a variety of conditions such as increased secretion,
      altered nitrogen source, heat shock, and decreased Ca2+ levels, indicating that
      anxC3.1 is constitutively expressed. This is the first reported functional
      characterisation of a fungal annexin.

PMID- 15451116
TI  - Multiple ubiquitin-specific protease genes are involved in degradation of yeast
      tryptophan permease Tat2 at high pressure.
AB  - When Saccharomyces cerevisiae cells are exposed to high hydrostatic pressure,
      tryptophan permease Tat2 is degraded in a manner dependent on Rsp5 ubiquitin
      ligase. Consequently, cell growth is arrested in tryptophan auxotrophic strains.
      Here we show that of 17 ubiquitin-specific protease genes (UBP), deletion of
      DOA4, UBP6 or UBP14 causes stabilization of Tat2 and hence the cells can grow at
      25 MPa. These disruptant cells displayed marked sensitivity to the arginine
      analogue canavanine. Internal free ubiquitin decreased 2- to 5-fold upon UBP
      deletion, although overproduction of ubiquitin did not affect their high-pressure
      growth and canavanine sensitivity. These results suggest that multiple ubiquitin
      specific proteases are involved in pressure-induced degradation of Tat2, rather
      than free ubiquitin depletion.

PMID- 15451117
TI  - Development of PCR assay based on ITS2 rDNA polymorphism for the detection and
      differentiation of Fusarium sporotrichioides.
AB  - A polymerase chain reaction assay was developed for detection of Fusarium
      sporotrichioides, a plant pathogen in many parts of the world. Based on small
      nucleotide differences in ITS2 (Internal Transcribed Spacer) rDNA of our local
      isolate of F. sporotrichioides (Accession No. AY510069) and other isolates found
      in NCBI/GeneBank database, species specific primer FspITS2K was selected. Primer
      pair FspITS2K and P28SL amplified a fragment of 288 bp containing a portion of
      ITS2 and 28S rDNA of all the F. sporotrichioides isolates tested, originated from
      different hosts and regions of the world but did not amplify any other species of
      Fusarium and plant's DNA. To use the PCR assay in seed health testing, a protocol
      was setup for the rapid and effective preparations of fungal DNA from wheat
      seeds. The method developed may be useful for the rapid detection and
      identification of F. sporotrichioides both from culture and from plant tissue.

PMID- 15451118
TI  - Blastomyces dermatitidis produces melanin in vitro and during infection.
AB  - Melanin is made by several important pathogenic fungi and is implicated in the
      pathogenesis of a number of mycoses. This study investigates whether the
      thermally dimorphic fungal pathogen Blastomyces dermatitidis produces melanin.
      Using techniques developed to study melanization in other fungi, we demonstrate
      that B. dermatitidis conidia and yeast produce melanin in vitro and that yeast
      cells synthesize melanin or melanin-like pigment in vivo. Melanization reduced
      susceptibility to amphotericin B, but not to itraconazole or voriconazole. Since
      melanin is an important virulence factor in other pathogenic fungi, this pigment
      may affect the pathogenesis of blastomycosis.

PMID- 15451119
TI  - Engineered Aeromonas hydrophila for enhanced production of poly(3-hydroxybutyrate
      co-3-hydroxyhexanoate) with alterable monomers composition.
AB  - Aeromonas hydrophila 4AK4 produces poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)
      (PHBHHx) containing 3-hydroxybutyrate (3HB) and about 15 mol% 3-hydroxyhexanoate
      (3HHx) from dodecanoate. To study the factors affecting the monomer composition
      and PHBHHx content, genes encoding phasin (phaP), PHA synthase (phaC) and (R)
      specific enoyl-CoA hydratase (phaJ) from Aeromonas punctata (formerly named
      Aeromonas caviae) were introduced individually or jointly into A. hydrophila
      4AK4. The phaC gene increased 3HHx fraction more significantly than phaP, while
      phaJ had little effect. Expression of phaC alone increased the 3HHx fraction from
      14 to 22 mol%. When phaC was co-expressed with phaP and phaJ, the 3HHx fraction
      increased from 14 to 34 mol%. Expression of phaP or phaC alone or with another
      gene enhanced PHBHHx content up to 64%, cell dry weight (CDW) as much as 4.4 gL(
      1) and PHBHHx concentration to 2.7 gL(-1) after 48 h in shake flask culture. The
      results suggest that a higher PHA synthase activity could lead to a higher 3HHx
      fraction and PHBHHx content. Co-expression of phaJ with phaC or phaP would favor
      PHA accumulation, although over-expression of phaJ did not affect PHA synthesis
      much. In addition, inhibition of beta-oxidation by acrylate in A. hydrophila 4AK4
      enhanced PHBHHx content. However, no monomers longer than 3HHx were detected. The
      results show that genetic modification of A. hydrophila 4AK4 enhanced PHBHHx
      production and altered monomer composition of the polymer.

PMID- 15451120
TI  - Potentially modifiable psychosocial factors associated with alcohol use during
      early adolescence.
AB  - This study was conducted to identify factors associated with alcohol use among
      early adolescents. A survey was administered to all Grade 7 and 8 students in 16
      Vermont school districts. The questionnaire covered demographics, alcohol,
      tobacco, and marijuana use, and measures of psychosocial mediators of alcohol use
      drawn from social cognitive theory. These included positive and negative
      expectancies about alcohol effects, perceived peer and parent alcohol norms,
      perceived prevalence of adolescent alcohol use, and confidence in ability to
      refuse alcohol. Of the 2919 respondents, 29% reported having at least one drink
      of beer in the preceding 30 days. In logistic regression, factors independently
      related to risk of drinking beer in the past 30 days were smoking (odds ratio
      [OR] = 2.3, 95% confidence interval [CI] 1.8-3.0), marijuana use (OR 3.9, 95% CI
      3.0-5.2), negative expectancies (OR 0.4, 95% CI 0.3-0.6), parent norms (OR 1.4,
      95% CI 1.1-1.7), and estimated percentage of high school students who drink (OR
      1.3, 95% CI 1.1-1.5). Gender, positive alcohol expectancies, and lack of
      confidence in ability to refuse alcohol all significantly interacted with peer
      norm, with these items more strongly associated with alcohol use when peer norm
      is toward "shouldn't drink." Modifiable perceptions of alcohol use were strongly
      associated with actual use in this adolescent sample, providing a basis for
      intervention program design.

PMID- 15451121
TI  - Major depression among adolescent smokers undergoing treatment for nicotine
      dependence.
AB  - This is the first study to examine the prevalence and effects of major depression
      (MDD) in a sample of adolescent smokers (N = 211) undergoing treatment for
      nicotine dependence. We assessed MDD at baseline and end of treatment with the
      mood disorders portion of the Structured Clinical Interview for the Diagnostic
      and Statistical Manual of Mental Disorders, fourth edition (DSM-IV). Eleven
      percent of participants reported a history of MDD (6% of males and 21% of
      females). Study variables did not distinguish those with and without a history of
      MDD. End of treatment abstinence rates and relapse rates were similar in both
      groups. Two participants (1%), both female, experienced onset of MDD during the
      treatment. The findings provide further evidence that MDD is a comparatively
      common disorder among children and adolescents and that clinicians should monitor
      and be prepared to respond to depression that may emerge during the treatment of
      nicotine-dependent adolescents.

PMID- 15451122
TI  - Concordance of different measures of nicotine dependence: two pilot studies.
AB  - Two samples of adult daily smokers completed a structured interview to determine
      nicotine dependence according to generic (DSM-IV/ICD-10), Fagerstrom [Fagerstrom
      Tolerance Questionnaire (FTQ), Fagerstrom Test for Nicotine Dependence (FTND),
      Heavy Smoking Index (HSI), and time to first cigarette after awakening (TFC)],
      consumption [e.g., cigarettes/day (CPD)], and self-rating (e.g., "how addicted
      are you") measures. One sample was a population-based sample of 43 smokers from
      the Vermont site of the DSM-IV field trial for substance use disorders. The other
      sample consisted of 50 smokers evenly distributed across a wide range of CPD to
      study biochemical markers of smokers. In the first study, DSM/ICD criteria were
      only slightly correlated with Fagerstrom (r =.24-.35) and consumption (r =.06
      0.33) criteria. Self-rating criteria were correlated moderately with most other
      criteria (r =.24-.60). In the second study, generic, Fagerstrom, and self-rating
      criteria increased with increasing CPD up to 30 CPD but not thereafter. One
      interpretation of these results is that generic, Fagerstrom, consumption, and
      self-rating criteria each tap different aspects of nicotine dependence.

PMID- 15451123
TI  - Deficits in plasma oxytocin responses and increased negative affect, stress, and
      blood pressure in mothers with cocaine exposure during pregnancy.
AB  - In animals, oxytocin enhances maternal behavior and lowers blood pressure (BP)
      and negative affect, while parturitional cocaine disrupts oxytocin activity and
      increases maternal neglect and aggression. Thus, we compared oxytocin, BP,
      maternal behavior, and affect in mothers of infants who used cocaine (cocaine, n
      = 10) or did not (no drug, n = 25) during pregnancy. Laboratory BP and
      circulating oxytocin, catecholamines, and cortisol were examined before and
      during a speech stressor on 2 days, with vs. without prestress baby holding.
      Ambulatory monitoring assessed BP, urinary norepinephrine, and cortisol for 24 h
      at home. The cocaine group had lower oxytocin levels, greater hostility and
      depressed mood, less support from others and mastery over life events, higher BP
      during all events of testing without the baby, and higher ambulatory BP and
      urinary norepinephrine at home, while cortisol and epinephrine responses were
      blunted. Although they tended to hold their babies less often at home, baby
      holding in the laboratory led to decreased BP in cocaine mothers who then did not
      differ from no-drug mothers in BP or observed affect.

PMID- 15451124
TI  - Correlates of adherence with transdermal nicotine.
AB  - This correlational study examined the adherence rates of transdermal nicotine
      (TN) use among a population of males and females 18 years of age and older (N =
      619) who received varying levels of behavioral intervention. Rates of patch
      adherence were assessed for demographic (e.g., gender, ethnicity, and age),
      income-, smoking- [e.g., baseline carbon monoxide (CO), nicotine dependence, and
      follow-up quit status], and treatment-related (e.g., condition, and drop status)
      variables. Loglinear and logistic regression analyses were performed to assess
      adherence rates. Results indicated that male gender [chi2(2, n = 485) = 20.39, P
      = .038], not dropping out of the study [chi2(2, n = 485) = 13.94, P < .001], and
      intensive treatment (compared to the standard care) [chi2(4, n = 485) = 14.96, P
      = .005] were associated with greater adherence to TN. Furthermore, patch
      adherence was associated with quit status at 6 months (OR = 2.47, CI = 1.56-3.91,
      P < .001) and 12 months (OR = 2.12, CI = 1.34-3.37, P = .001). Complete and
      partial patch adherence (compared to minimal/no adherence) were associated with a
      greater number of telephone intervention contacts completed (OR = 2.621, CI =
      1.421-4.832, P = .002). Noteworthy however, was the lack of association between
      level of income and patch adherence. These findings suggest characteristics of
      those more and less likely to adhere to TN in research and clinical settings.

PMID- 15451125
TI  - Cigarette smoking, ambulatory cardiovascular monitoring, and mood in Vietnam
      veterans with and without chronic posttraumatic stress disorder.
AB  - This study investigated the association among cigarette smoking, posttraumatic
      stress disorder (PTSD), and ambulatory cardiovascular and mood monitoring in 117
      male Vietnam combat veterans (61 with PTSD and 56 without PTSD). Positive smoking
      status was associated with higher systolic blood pressure (SBP) and heart rate
      (HR), as well as greater diastolic blood pressure (DBP) variability. Compared to
      individuals without PTSD, PTSD patients had higher HR, anger/hostility ratings,
      and depression/anxiety ratings. Significant diagnosis by smoking status
      interactions were found indicating that compared to nonsmokers with PTSD, smokers
      with PTSD had higher DBP, mean arterial pressure (MAP), and positive affect. Ad
      lib cigarette smoking during the previous 30 min did not have a significant
      effect on mood or cardiovascular parameters, except in non-PTSD smokers who
      reported lower depression/anxiety ratings after smoking. Findings suggest that
      the effect of smoking on cardiovascular parameters may be amplified in smokers in
      PTSD. Findings suggest that the interrelationships among cardiovascular
      parameters, cigarette smoking, and PTSD deserve more research attention.

PMID- 15451126
TI  - Alcohol consumption, cigarette smoking, and subjective health in Korean elderly
      men.
AB  - The purpose of the study was to investigate the level of alcohol drinking,
      cigarette smoking, and subjective health in elderly Korean men and to examine the
      relationships among those variables. The data were collected through the
      questionnaire that includes general characteristics, the quantity-frequency (Q-F)
      method, and the Fagerstrom Tolerance Questionnaire (FTQ) scale. The prevalence of
      alcohol consumption was 65.2%, and 28.7% represented heavier drinkers. The
      prevalence of smoking was 47.0%. Among the smokers, 17.1% elderly men reported
      nicotine dependence in the medium range. Forty-six percent of subjects reported
      their health as poor or fair. In conclusion, alcohol drinking and smoking were
      prevalent among Korean elderly men. These findings show the need to improve
      strategies for educating elderly men and motivating them to incorporate healthy
      behaviors.

PMID- 15451127
TI  - Cognitive functioning moderates the relation between Attention Deficit
      Hyperactivity Disorder symptoms and alcohol use in women.
AB  - Previous work revealed that cognitive functioning moderated the relation between
      Attention Deficit Hyperactivity Disorder (ADHD) Symptoms and alcohol use
      [Alcohol., Clin. Exp. Res. 23 (1999) 224]. ADHD Symptoms correlated significantly
      with alcohol use for individuals with a poorer performance on tasks assessing
      prefrontal area functioning but not for individuals with higher scores on these
      tasks. The current study proposes to replicate this previous work and extend it
      in three ways. These include using a sample consisting solely of women, including
      the current DSM-IV [American Psychiatric Association (1994). Diagnostic and
      statistical manual of mental disorders (4th ed., revised). Washington, DC:
      Author] criteria for ADHD, and increasing the number of measures to assess
      cognitive functioning and drinking habits. Eighty-two female undergraduates
      completed four measures of alcohol use, three measures of ADHD, and six measures
      of cognitive functioning. Stacked two-group analyses replicated the previous
      moderator effect. Alcohol use and ADHD symptoms correlated .31 (ns) for the
      individuals who scored higher on the neuropsychological tasks. However, these
      constructs correlated .53 (P < .05) for individuals with lower scores on these
      tasks. Better performance on tasks assessing prefrontal area functioning may
      protect individuals from drinking in accordance with their ADHD symptoms.

PMID- 15451128
TI  - Explaining adolescents' smoking and drinking behavior: the concept of smoker and
      drinker prototypes in relation to variables of the theory of planned behavior.
AB  - Research has demonstrated that social image factors play an important role in the
      course of adolescent's substance use, that is, smoking and drinking. The concept
      of social images or prototypes is embedded into a theoretical model called the
      prototype/willingness model. The present study addresses the relative value of
      the prototype/willingness model in relation to the theory of planned behavior. To
      study relations between prototypes and adolescents' willingness and intention to
      engage in smoking and drinking behavior, cross-sectional data among 2814
      adolescents (12-16 years) were gathered. Results show that adolescents describe
      daily-smoking and weekly-drinking peers generally as slightly well adjusted,
      slightly rebellious, not really cool, and not really attractive. Positive
      relations were observed between smoker and drinker prototypes and adolescents'
      intention and willingness to smoke and drink in the future. Furthermore,
      regression analyses showed that prototypes of daily-smoking and weekly-drinking
      peers explained a significant part of the variance in intention and willingness
      to smoke and drink, and added significantly to the variance explained by the
      variables of the theory of planned behavior.

PMID- 15451129
TI  - Predictors of substance use over time among gay, lesbian, and bisexual youths: an
      examination of three hypotheses.
AB  - Gay, lesbian, and bisexual (GLB) youths report elevated levels of substance use
      relative to heterosexual youths, but reasons for this disparity have received
      scant attention. This report longitudinally examined three hypothesized
      explanations for cigarette, alcohol, and marijuana use among 156 GLB youths.
      Counter to two hypotheses, neither a history of childhood sexual abuse nor recent
      experiences of gay-related stressful life events were associated with increased
      substance use over time. However, the hypothesis concerning the coming-out
      process was supported by significant nonlinear associations of involvement in gay
      related (recreational and social) activities with changes in alcohol use at 12
      months and changes in marijuana use at 6 months and 12 months. Specifically, as
      involvement in gay-related activities increased, alcohol and marijuana use was
      found to initially increase, but then, substance use declined as involvement in
      gay-related activities continued to increase. These findings offer a potential
      explanation for high levels of substance use among GLB youths and suggest
      potential areas for intervention to prevent or decrease substance use among these
      youths.

PMID- 15451130
TI  - Parental alcoholism: relationships to adult attachment in college women and men.
AB  - The present study of general and romantic adult attachment among 484 female and
      male college students compared those who resided with an alcohol-abusing parent
      prior to age 16 and those who did not. Participants completed the Relationship
      Style Questionnaire (RSQ; general adult attachment), Experiences in Close
      Relationships-Revised (ECR-R; romantic attachment), and the Children of Alcoholic
      Screening Test (CAST; perceived parental alcoholism). Results indicated that 23%
      of these young adults had lived with an alcohol-abusing parent, and relative to
      those who had not, they reported more anxiety and greater avoidance in romantic
      relationships and a more fearful style of general adult attachment. The
      implications of these findings in the context of the extant literature were
      discussed.

PMID- 15451131
TI  - Weight concerns among male smokers.
AB  - Many smokers perceive that smoking controls their body weight and that stopping
      smoking leads to weight gain. This study examined characteristics associated with
      weight concerns in 72 male smokers enrolled in a controlled trial for smoking
      cessation. Motivation to quit smoking was found to be significantly lower in
      those with weight concerns (P < .001). Further investigation is needed to enable
      the tailoring of interventions for weight-concerned male smokers.

PMID- 15451132
TI  - Risk-taking propensity and risky sexual behavior of individuals in residential
      substance use treatment.
AB  - In the current study, a battery of self-report measures of impulsivity, self
      esteem, and depressive symptoms, as well as a behavioral measure of risk-taking
      propensity, was administered to 76 residents of two inner-city substance use
      residential treatment programs to determine the unique relationship between risk
      taking propensity and risky sexual behavior (RSB). Results indicated that
      impulsivity, self-esteem, and risk-taking propensity were independently related
      to RSB. In a subsequent regression analysis, risk-taking propensity evidenced
      incremental validity, suggesting a relationship between risk-taking propensity
      and RSB, above and beyond that provided with the other relevant variables. The
      potential importance of risk-taking propensity the better understanding HIV risk
      through engagement in RSB is discussed.

PMID- 15451133
TI  - Impact of a motivational intervention on mechanisms of change in low-income
      pregnant smokers.
AB  - Numerous smoking cessation interventions targeting pregnant women have been
      developed and tested. An overall increase in smoking cessation is indicated, yet
      quit rates are modest and variable. Although efficacious with other substance
      abuse populations, motivational interviewing (MI) interventions with pregnant
      smokers have resulted in marginal outcomes. Examining treatment mechanisms
      affected by MI interventions may assist in understanding negative results and in
      developing more innovative and effective interventions. This study assessed the
      impact of an MI intervention on transtheoretical (TTM)-based mechanisms of change
      in low-income pregnant smokers (N = 54). Repeated measures analyses indicated
      that relative to usual care (UC), pregnant smokers who received MI reported a
      greater increase in confidence to abstain from smoking, a decrease in temptation
      to smoke, and a decrease in level of depression. However, the MI intervention was
      not associated with forward progression in the stages of change. More intensive
      motivational and cognitive-behavioral interventions demonstrated effective in
      nonpregnant, smoking populations, with more frequent sessions separate from
      prenatal visits, are recommended to further increase smoking cessation rates
      among low-income pregnant smokers.

PMID- 15451134
TI  - Substance use among school-based youths in Puerto Rico: differences between
      gender and grade levels.
AB  - The present study examined substance use rates among adolescents in Grades 7-12
      in Puerto Rico. Nine hundred eighty-nine students completed the Spanish version
      of the International Survey of Adolescent Health. More than 50% of middle school
      youths and 75% of high-school youths reported lifetime alcohol use. Female gender
      was associated with tobacco use in middle school while male gender was associated
      with marijuana use in high school. High-school females reported lower rates of
      tobacco use and marijuana use than middle-school females. High-school males
      exhibited substantially higher drug-use rates than middle-school males for each
      substance. These findings may suggest that universal drug prevention
      interventions may be needed for females in Puerto Rico before they enter middle
      school, while targeted interventions aimed at high-risk females who continue to
      smoke tobacco or marijuana may be more effective during high school. In contrast,
      targeted drug prevention interventions for males probably need to begin in middle
      school and be maintained if not increased in intensity throughout the high-school
      years.

PMID- 15451135
TI  - Substance use and posttraumatic stress disorders: symptom interplay and effects
      on outcome.
AB  - This study examined concurrent and prospective associations between substance use
      disorder (SUD) and posttraumatic stress disorder (PTSD) diagnosis and symptoms
      and mechanisms underlying these associations. Participants (n = 133) were
      assessed at intake and 6 months following inpatient SUD treatment. Patients
      differed by baseline PTSD status on psychiatric comorbidity and substance use
      history but not on current substance use symptoms. Participants with alcohol use
      disorders reported a greater number of reexperiencing symptoms. Baseline PTSD
      status did not predict substance use outcome. However, change in PTSD status over
      follow-up predicted substance use outcomes; those with unremitted PTSD
      demonstrated poorer SUD outcome than those with remitted PTSD. General
      psychiatric distress at follow-up was associated with poorer outcomes, and such
      distress mediated the association between PTSD change status and substance use
      outcome. Findings suggest that clinicians should assess for PTSD among those with
      SUD and, during treatment, should monitor PTSD and other psychological symptoms,
      which may be risk factors for relapse to substance abuse.

PMID- 15451136
TI  - Salivary cortisol concentrations are associated with acute nicotine withdrawal.
AB  - Research has shown that smoking commercial cigarettes results in slight
      elevations in cortisol levels relative to smoking nicotine-free cigarettes. It is
      not clear however, whether cortisol concentrations are associated with nicotine
      withdrawal symptoms among regular cigarette smokers. Nicotine withdrawal symptoms
      resemble a stress response, and may therefore contribute to cortisol production.
      This preliminary study focuses on assessing the association between salivary
      cortisol levels and subsequent levels of self-reported withdrawal and craving
      symptoms. Twenty male smokers were studied during a 4-h deprivation period. All
      participants smoked an initial cigarette shortly after arrival and were informed
      that they would be unable to smoke for the remainder of the session. The session
      consisted of each participant watching a movie, and then waiting in the
      laboratory for two consecutive 30-min intervals. Self-reported nicotine
      withdrawal and craving were assessed four times and salivary cortisol, five
      times, during the session. Results show that baseline cortisol concentrations
      predicted subsequent withdrawal symptoms and craving measured using the Tobacco
      Withdrawal Symptom Checklist (WSC). This suggests that salivary cortisol may
      contribute to, or be a marker of, nicotine withdrawal symptoms.

PMID- 15451137
TI  - Comparison of smoking relapse curves among African-American smokers.
AB  - We examined the smoking relapse curves for African-American smokers by level of
      smoking to characterize nicotine dependence in this population of smokers. This
      analysis was conducted from data originally collected to study differences in
      level of smoking among African-Americans at an inner-city health center in
      Midwest. Relatively little research has been conducted to clarify smoking and
      quitting patterns among African-American smokers. The median number of cigarettes
      smoked currently was 7 cigarettes per day (cpd) for light smokers and 20 cpd for
      the moderate to heavy smokers. The heavier smokers reported smoking at this rate
      longer than light smokers, 11 and 5 years, respectively. The major finding in
      this study is that African-American light smokers have abstinence rates very
      similar to heavier smokers and the median length of their most recent quit
      attempts were also similar. Therefore, stable light smokers may also need smoking
      cessation interventions similar to those used for heavier smokers in order to
      successfully stop smoking.

PMID- 15451138
TI  - Using the NORC DSM Screen for Gambling Problems as an outcome measure for
      pathological gambling: psychometric evaluation.
AB  - The National Opinion Research Center DSM Screen for Gambling Problems (NODS), a
      population-based telephone-screening tool to identify gambling problems according
      to DSM-IV criteria, was examined as a potential outcome measure for gambling
      treatment studies. The NODS was administered to problem gamblers as part of a 1
      year follow-up after a brief treatment. Internal reliability was fair to good and
      the factor structure and item-total correlations supported the existence of a
      single construct with three subfactors, measuring negative behavioral
      consequences, preoccupation and impaired control over gambling and tolerance, and
      withdrawal and relief gambling. The NODS total score correlated moderately with
      gambling behavior and outcome as predicted. The total score also correlated
      highly with the total score of the South Oaks Gambling Screen (SOGS) although the
      NODS and SOGS categorization of nonproblem, problem, and pathological gamblers
      showed poor agreement. The NODS, as designed, provided a more strict definition
      of disordered gambling than the SOGS. In summary, the NODS shows promise as an
      outcome measure of gambling problems.

PMID- 15451139
TI  - Social climate and workplace drinking among women in a male-dominated occupation.
AB  - OBJECTIVE: This study applies Gilligan's relational theory to an exploration of
      the influence of the social climate at work on workplace drinking in a male
      dominated occupation. METHODS: Data used in this analysis were originally
      collected from a random sample of employees at a heavy machinery assembly plant
      (N = 984, women = 121). Because reciprocal relationships between workplace
      drinking and social climate were hypothesized, the parameters were estimated
      using simultaneous equation modeling. RESULTS: Women who reported a negative
      social climate at work also had a greater propensity to drink at work. There was
      no similar relationships between social climate and workplace drinking for men.
      CONCLUSIONS: Workplace drinking prevention programs in male-dominated occupations
      may need to address the social climate at work, particularly for women.

PMID- 15451140
TI  - HIV infection and high-risk behaviors in opioid dependent patients: the Indian
      context.
AB  - Various risk behaviors promote the spread of HIV in drug addicts. Reflecting the
      substantial regional and geographic differences in the impact of HIV, its
      prevalence rates vary from country to country. In view of increasing reports of
      injection drug-uses (IDUs) from different parts of India, the study was aimed to
      examine and investigate the difference in prevalence rates of seropositivity
      between IDUs and non-IDUs in patients of drug dependence and to compare the
      pattern of risk behaviors due to sexual and drug use practice in IDUs and non
      IDUs. A high HIV seroprevalence of 8.3% between IDUs and 1.8% in non-IDUs was
      found. The study findings suggest a trend towards drug-related risks being higher
      than sex-related risks in IDUs.

PMID- 15451141
TI  - Enoxaparin in non-ST segment elevation acute coronary syndromes: duration of
      therapy is essential to benefit.

PMID- 15451142
TI  - More bad news about atrial fibrillation.

PMID- 15451143
TI  - Hearts and minds: psychological factors and the chest pain of cardiac syndrome X.

PMID- 15451144
TI  - Isoprostanes, emerging biomarkers and potential mediators in cardiovascular
      diseases.

PMID- 15451145
TI  - Inflammation and restenosis after percutaneous coronary interventions.
AB  - The role of inflammation in the development of restenosis after percutaneous
      coronary interventions has been investigated in several studies. There is an
      interaction of inflammatory activation and vascular wall response to injury
      leading to intimal hyperplasia. Percutaneous interventions trigger inflammatory
      reactions leading to the development of intimal hyperplasia. This reaction is
      even more prominent in atheromatic plaques in which inflammatory cells have
      already been activated. In the clinical setting there are several methods for the
      recognition of the inflammatory activation. In this article we review the data
      for the role of inflammatory process in restenosis and the significance of
      identifying the inflamed lesions prior to the intervention. Moreover, the
      therapeutic implications for the inhibition of inflammatory activation are
      mentioned.

PMID- 15451146
TI  - Enoxaparin versus unfractionated heparin in patients treated with tirofiban,
      aspirin and an early conservative initial management strategy: results from the A
      phase of the A-to-Z trial.
AB  - AIMS: In high risk patients with non-ST elevation acute coronary syndromes (ACS),
      enoxaparin is generally preferred to unfractionated heparin (UFH). However, less
      is known about the relative merits of these two forms of heparin in patients
      receiving concomitant glycoprotein IIb/IIIa inhibitors. METHODS AND RESULTS: The
      A phase of the A-to-Z trial was an open label non-inferiority trial in which 3987
      patients with non-ST elevation ACS were randomised to receive either enoxaparin
      or UFH in combination with aspirin and tirofiban. Inclusion required either ST
      depression or cardiac biomarker elevation. While the selection of an early
      management strategy (invasive or conservative) was at the discretion of the local
      investigator, investigators were asked to designate their plans for an invasive
      or conservative strategy on the case record form. An early conservative strategy
      was specified for 1778 patients (45%); this subgroup forms the population for the
      present analyses. Among patients with a planned conservative strategy, baseline
      characteristics were similar between those randomised to UFH (n = 872) and those
      randomised to enoxaparin (n = 906). The primary endpoint of death, new MI, or
      documented refractory ischaemia within 7 days of randomisation occurred in 10.6%
      of patients randomised to UFH and 7.7% of patients randomised to enoxaparin (HR
      0.72; 95% CI 0.53-0.99; p = 0.04). The combined rate of TIMI major, minor, or
      loss no-site bleeding was 1.3% in patients treated with UFH and 1.8% in those
      treated with enoxaparin (p = ns). CONCLUSIONS: When a conservative approach to
      catheterisation and PCI was planned for ACS patients receiving tirofiban and
      aspirin, enoxaparin was associated with superior efficacy and similar bleeding vs
      UFH.

PMID- 15451147
TI  - Distinct psychosocial differences between women with coronary heart disease and
      cardiac syndrome X.
AB  - AIMS: To compare the impact of oestrogen, gynaecological history, social support,
      life events and family history of CHD on psychosocial morbidity in syndrome X,
      CHD patients and healthy controls. METHODS AND RESULTS: 100 female syndrome X (60
      +/- 9 years), 100 female CHD (65 +/- 9 years) and 100 healthy female volunteers
      (61 +/- 10 years) completed the hospital anxiety and depression scale (HADS),
      health anxiety questionnaire (HAQ), a demographic information scale, life events
      scale, family history of CHD, menopausal, menstrual and gynaecological history. A
      17beta-oestradiol sample was taken. Syndrome X patients had higher levels of life
      interference (p < 0.05) and HADS anxiety (p < 0.05) than CHD patients, and higher
      levels of all HADS and HAQ scales than controls (p < 0.01). Syndrome X patients
      with a large social network had lower HADS anxiety (p < 0.05), health worry (p <
      0.05), life interference (p < 0.01) and total HAQ (p < 0.01). Social network (p =
      0.003), divorced/separated or widowed status (p = 0.005), HRT (p = 0.008) and
      HADS anxiety score (p < 0.001) accounted for 41.9% of the variance in HAQ scores
      in syndrome X. Oestrogen was unrelated to the HADS or HAQ for any group.
      CONCLUSION: Syndrome X patients suffered higher levels of psychological morbidity
      in comparison to CHD patients and controls. Life events and social network size
      were related to health anxiety, general anxiety and depression in women with
      syndrome X.

PMID- 15451148
TI  - Severity of heart failure, treatments, and outcomes after fibrinolysis in
      patients with ST-elevation myocardial infarction.
AB  - AIMS: To define the clinical characteristics, co-morbidities, treatment, and
      clinical outcomes of patients with varying degrees of heart failure (HF)
      complicating ST-elevation myocardial infarction (STEMI), and to identify patients
      at high risk for HF following fibrinolysis. METHODS AND RESULTS: 15,078 STEMI
      patients enrolled in a worldwide fibrinolytic trial (InTIME-II) were categorised
      into one of four hierarchical, mutually exclusive groups of HF: shock (n = 719,
      5%); severe HF (n = 1082, 7%); mild HF (n = 1619, 11%); no HF (n = 11,658, 77%).
      In a multivariable model, anterior MI (OR 1.8, 95% CI [1.6; 1.9]), age > or = 65
      (OR 1.8 [1.6; 2.0]), prior HF (OR 3.3 [2.6; 4.2]), and creatinine clearance < 60
      mL/min (OR 1.8 [1.6; 2.1]) were the four most powerful correlates of HF. Although
      30-day mortality was sixfold higher for patients with HF (18.9% vs. 3.1%, P <
      0.0001), these patients were less likely to undergo angiography (30% vs. 40%, P <
      0.0001) and revascularisation (19% vs. 25%, P , 0.0001), than patients without
      HF. Likewise, angiotensin-inhibitors and beta-blockers were not optimally
      utilised in patients with HF following MI. CONCLUSIONS: During the index
      admission following fibrinolysis 23% of patients had HF. Despite a higher risk
      profile, patients with more severe HF were treated less aggressively than
      patients without HF.

PMID- 15451149
TI  - Effect of age on short and long-term mortality in patients admitted to hospital
      with congestive heart failure.
AB  - AIMS: To describe the association between age and risk factors in patients
      hospitalised with congestive heart failure (CHF) and to determine the effect of
      age on mortality. METHODS AND RESULTS: Consecutive patients admitted to 34
      hospitals with CHF during a period of 2 years were registered. Mean age was
      71.7+/-10.2 years, 60% were male and 63% were in NYHA class III-IV. Moderate to
      severe left ventricular (LV) systolic dysfunction was present in 41%. Short and
      long-term survival status was obtained after 30 days and 5-8 years, respectively.
      Older patients less frequently had LV systolic dysfunction, were under treated
      with ACE-inhibitors and were more often female. The prevalence of hypertension,
      diabetes and ischaemic heart disease increased with age, until the oldest age
      group (>80 years). Age was an independent predictor of short-term mortality (risk
      ratio (RR) per 10-year increase was 1.23 (95% CI 1.04-1.47)). Advancing age
      significantly increased long-term mortality (RR 1.55 (1.50-1.61)). Age interacted
      with the LV ejection fraction (P = 0.003). In patients with LV systolic
      dysfunction, the RR per 10-year increase was 1.29 (1.19-1.39) whereas in patients
      with preserved systolic function the RR was 1.57 (1.43-1.72, multivariate
      analyses). CONCLUSION: The clinical characteristics of CHF patients vary
      considerably with age. Elderly patients hospitalised with CHF face a very grave
      prognosis, particularly if their heart failure symptoms are caused by LV systolic
      dysfunction.

PMID- 15451150
TI  - Patient differences related to management in general practice and the hospital: a
      cross-sectional study of heart failure in the community.
AB  - AIM: To compare patients treated for heart failure in relation to the management
      in general practices versus hospital admission. METHODS AND RESULTS: Twelve
      randomly selected general practices (GP) were screened for patients receiving ACE
      inhibitor, digoxin, or loop diuretic treatment. The first 500 volunteers of 959
      potential subjects were invited to a cardiac examination after exclusion of 235
      frail, physically or mentally disabled patients. A diagnosis of heart failure
      during hospital admission (Hospital-HF, n = 102) was more related (p < 0.05) to
      male sex (45% vs. 21%), advanced age (73 vs. 70 years), breathlessness (75% vs.
      62%), LV systolic dysfunction (47% vs. 20%), objective cardiac abnormality (92%
      vs. 65%) and higher 4-year mortality (33% vs. 15%) than patients taking loop
      diuretics due to signs and symptoms of heart failure in GP (GP-HF). Patients
      without clinical heart failure (n = 301) had the same survival but less symptoms
      and cardiac abnormalities than GP-HF patients. CONCLUSION: A surplus morbidity
      and mortality was related to a hospital-based rather than a GP based diagnosis of
      HF. Patients managed in GP were different from patients entering previous
      clinical trials of heart failure. We estimate that the pool of patients
      hospitalised with systolic heart failure would be increased from 1.3 to 1.4 more
      if all patients from primary care were included.

PMID- 15451151
TI  - Sympathetic reinnervation, exercise performance and effects of beta-adrenergic
      blockade in cardiac transplant recipients.
AB  - AIMS: To evaluate effects of beta-adrenergic receptor blockade on allograft
      performance, and to correlate these effects with sympathetic reinnervation.
      METHODS AND RESULTS: Myocardial catecholamine storage capacity was determined in
      12 non-rejecting transplant recipients using PET and C-11 adrenaline
      (epinephrine). Haemodynamics and left ventricular function were measured using
      radionuclide angiography at rest and during symptom-limited exercise before and
      after non-selective beta-blockade (propranolol iv). Exercise time and stress
      induced increases of heart rate and LVEF before beta-blockade were significantly
      higher in reinnervated compared to denervated recipients. While resting LVEF
      remained unchanged, heart rate and blood pressure were generally reduced by beta
      blockade, which was well tolerated by all patients. Exercise time and increases
      of heart rate and LVEF were more attenuated in reinnervated recipients.
      Differences of chronotropic and inotropic response to exercise between groups
      were no longer present following beta-blockade. Correlations between myocardial
      adrenaline retention, peak heart rate and increase of global, as well as regional
      ejection fraction during exercise were observed before, but not during beta
      blockade. CONCLUSION: Acute, non-selective beta-blockade is well tolerated by
      transplant recipients, but significantly attenuates beneficial functional effects
      of sympathetic reinnervation on exercise performance. The data suggest that
      reappearance of sympathetic nerve terminals is associated with reestablishment of
      intact pre-/postsynaptic interaction.

PMID- 15451152
TI  - Stroke patients with atrial fibrillation have a worse prognosis than patients
      without: data from the Austrian Stroke registry.
AB  - AIMS: Stroke patients with atrial fibrillation (AF) have a poorer neurological
      outcome than stroke patients without AF. Whether stroke patients with AF also
      have a higher rate of medical complications is unknown. The aim of the study was
      to compare the in-hospital course of acute stroke patients with and without AF.
      METHODS AND RESULTS: The Austrian Stroke registry was a prospective multi-centre
      study involving 57 medical departments documenting the hospital course of
      consecutive stroke patients from June 1999 to October 2000. AF was diagnosed in
      304 (31%) of 992 patients. Patients with AF were older (79 versus 75 years, p <
      0.0004) than no-AF patients. There were more cases of pneumonia (23% versus 9%, p
      < 0.0004), pulmonary oedema (12% versus 6%, p < 0.0004) and symptomatic
      intracerebral haemorrhage (8% versus 2%, p < 0.0004) in AF compared to no-AF. In
      hospital mortality was higher in AF (25% versus 14%, p < 0.0004), and
      neurological outcome was poorer (65 versus 90 Barthel index, p < 0.0004). On
      multivariable logistic regression analysis, however, AF was no predictor for
      mortality, but a Barthel index of zero (odds ratio 5.30, 95% CI 3.10-9.08, p <
      0.0001), a National Institutes of Health Stroke Scale > 21 or comatose (odds
      ratio 3.13, 95% CI 2.26-4.32, p < 0.0001), age > 75 years (odds ratio 3.15, 95%
      CI 1.85-5.37, p < 0.0001), heart rate > 100 min(-1) (odds ratio 2.15, 95% CI 1.26
      3.66, p = 0.0049), obstructive pulmonary disease (odds ratio 2.58, 95% CI 1.03
      6.48, p = 0.0442) and creatinine > 125 micromol/l (odds ratio 1.84, 95% CI 1.00
      3.37, p = 0.0479). CONCLUSION: Stroke in AF is associated with a poor prognosis,
      an increased rate of medical and neurological complications and a higher in
      hospital mortality than in no-AF.

PMID- 15451153
TI  - A randomized, double-blind, placebo-controlled study of permanent cardiac pacing
      for the treatment of recurrent tilt-induced vasovagal syncope. The vasovagal
      syncope and pacing trial (SYNPACE).
AB  - AIMS: Recently, some studies revealed the efficacy of pacemaker implantation in
      decreasing recurrences in patients with vasovagal syncope. As these studies were
      not blinded or placebo-controlled, the benefits observed might have been due to a
      bias in the assessment of outcomes or to a placebo effect of the pacemaker. We
      performed a randomized, double-blind, placebo-controlled study in order to
      ascertain if pacing therapy reduces the risk of syncope relapse. METHODS AND
      RESULTS: Twenty-nine patients (53 +/- 16 years; 19 women) with severe recurrent
      tilt-induced vasovagal syncope (median 12 syncopes in the lifetime) and 1
      syncopal relapse after head-up tilt testing underwent implantation of a
      pacemaker, and were randomized to pacemaker ON or to pacemaker OFF. During a
      median of 715 days of follow-up, 8 (50%) patients randomized to pacemaker ON had
      recurrence of syncope compared to 5 (38%) of patients randomized to pacemaker OFF
      (p = n.s.); the median time to first syncope was longer in the pacemaker ON than
      in pacemaker OFF group, although not significantly so (97 [38-144] vs 20 [4-302]
      days; p = 0.38). There was also no significant difference in the subgroups of
      patients who had had a mixed response and in those who had had an asystolic
      response during head-up tilt testing. CONCLUSION: Our data were unable to show a
      superiority of active pacing versus inactive pacing in preventing syncopal
      recurrence in patients with severe recurrent tilt-induced vasovagal syncope.

PMID- 15451154
TI  - Epidemiology and prognostic implications of syncope in young competing athletes.
AB  - AIMS: This study was undertaken to evaluate the epidemiological features and the
      prognostic implications of syncope in young athletes. METHODS AND RESULTS: A
      cohort of 7568 young athletes (5132 males, 2436 females, aged 16.2 +/- 2.4)
      underwent a pre-participation evaluation. A syncopal spell in the last 5 years
      was reported by 474 athletes (6.2%). Syncope was unrelated with exercise in 411
      athletes (86.7%), post-exertional in 57 (12.0%) and exertional in 6 (1.3%). All
      episodes of non-exertional or post-exertional syncope had the typical features of
      neurally-mediated fainting. The 6 athletes with exertional syncope underwent
      further testing allowing the diagnosis of hypertrophic cardiomyopathy in one
      case, and of right ventricular outflow tract tachycardia in another. The
      remaining 4 athletes only showed a positive response to tilt-testing. All
      athletes were followed for 6.4 +/- 3.1 years, during 48,066.6 person-years of
      follow-up. The recurrence rate was 20.3 per 1000 subject-years in athletes with
      non-exertional, and 19.2 per 1000 subject-years in athletes with post-exertional
      syncope. The incidence of first report of syncope was 2.2 per 1000 subject-years
      for non-exertional and 0.26 per 1000 subjects-years for post-exertional spells.
      No other adverse event was noted during follow-up. CONCLUSIONS: In young
      athletes, syncope occurring before the initial pre-participation screening has a
      neurally-mediated origin in most cases and shows a low recurrence rate. Exercise
      related syncope is infrequent and is not associated with an adverse outcome in
      subjects without cardiovascular abnormalities. The incidence of new syncope
      during competitive activity is particularly low.

PMID- 15451155
TI  - Cross-sectional evaluation of brachial artery flow-mediated vasodilation and C
      reactive protein in healthy individuals.
AB  - AIMS: The present study was designed to (a) examine the interrelationship between
      endothelial function and CRP in healthy individuals and (b) evaluate the
      relationship of each biomarker towards global Framingham risk scores. METHODS AND
      RESULTS: Brachial artery flow-mediated vasodilatation (FMD), CRP, and traditional
      cardiovascular risk factors were measured in the Firefighters and Their
      Endothelium (FATE) study, which recruited 1154 male participants (mean age 47.4+/
      9.8 years) with no known history of cardiovascular disease. No relationship was
      observed between FMD and CRP (p = 0.96). FMD and the Framingham risk score tended
      to correlate but not significantly (p = 0.07). A lower FMD was related to a
      higher systolic and diastolic blood pressure (p < 0.001 and p = 0.002,
      respectively) in the univariate analysis, and higher systolic blood pressure (p =
      0.001) in the multivariate analysis. Elevated CRP levels independently correlated
      most closely with overall Framingham risk score (r = 0.36, p < 0.001) and a
      weaker although statistically significant relationship was seen with individual
      traditional cardiovascular risk factors (p < 0.005). CONCLUSIONS: The current
      study provided evidence that brachial artery FMD had no relationship to CRP in a
      large cohort of healthy subjects. These observations suggest that the predictive
      value of CRP may be largely independent of abnormalities in endothelial function.
      The additive prognostic value of endothelial vasodilator testing remains to be
      established.

PMID- 15451156
TI  - Inflammation, arrhythmia burden and the thrombotic consequences of atrial
      fibrillation.

PMID- 15451157
TI  - Relationship between C-reactive protein concentrations during glucocorticoid
      therapy and recurrent atrial fibrillation.

PMID- 15451158
TI  - Anti-inflammatory medication for atrial fibrillation.

PMID- 15451159
TI  - A refined circular template matching method for classification of human
      cytomegalovirus capsids in TEM images.
AB  - An automatic image analysis method for describing, segmenting, and classifying
      human cytomegalovirus capsids in transmission electron micrograph (TEM) images of
      host cell nuclei has been developed. Three stages of the capsid assembly process
      in the host cell nucleus have been investigated. Each class is described by a
      radial density profile, which is the average grey-level at each radial distance
      from the center. A template, constructed from the profile, is used to find
      possible capsid locations by correlation based matching. The matching results are
      further refined by size and distortion analysis of each possible capsid,
      resulting in a final segmentation and classification.

PMID- 15451160
TI  - Computer simulation on fatigue behavior of cemented hip prostheses: a
      physiological model.
AB  - This paper is concerned with the investigation on the fatigue failure of implant
      fixation by numerical approaches. A computer algorithm based on finite element
      analysis and continuum damage mechanics was proposed to quantify the fatigue
      damage rate of cement mantle under physiological conditions. In examining the
      interfacial debonding effect, the interface elements were introduced at cement
      stem interfaces and calibrated with the increase of loading cycles. Current
      results reveal that the major sites for failure initiation are in the proximal
      anterior-medial regions and at the distal prosthesis tip, which clearly
      demonstrate the same failure scenario as observed in clinical studies. Such
      fatigue failures not only result in the corruption of cement-stem interfaces, but
      also greatly affect the cement stress distribution and the damage rate in
      subsequent loading cycles. Another significant result is that the predicted
      damage rate increases steadily with gait cycles. This trend in damage development
      is consistent with the findings obtained from fatigue tests available in
      literature. It is anticipated that presented methodology can serve as a pre
      clinical validation of cemented hip prostheses.

PMID- 15451161
TI  - Protein synthesis profiling in the developing brain: a graph theoretic clustering
      approach.
AB  - Mapping regional brain development in terms of protein synthesis (PS) activity
      yields insight on specific spatio-temporal ontogenetic patterns. The biosynthetic
      activity of an individual brain nucleus is represented as a time-series object,
      and clustering of time-series contributes to the problem of inducing indicative
      patterns of brain developmental events and forming respective PS chronological
      maps. Clustering analysis of PS chronological maps, in comparison with epigenetic
      influences of alpha2 adrenoceptors treatment, reveals relationships between
      distantly located brain structures. Clustering is performed with a novel graph
      theoretic clustering approach (GTC). The approach is based on the weighted graph
      arrangement of the input objects and the iterative partitioning of the
      corresponding minimum spanning tree. The final result is a hierarchical
      clustering-tree organization of the input objects. Application of GTC on the PS
      patterns in developing brain revealed five main clusters that correspond to
      respective brain development indicative profiles. The induced profiles confirm
      experimental findings, and provide evidence for further experimental studies.

PMID- 15451162
TI  - Quantifying agitation in sedated ICU patients using digital imaging.
AB  - Agitation is a significant problem in the Intensive Care Unit (ICU), affecting
      71% of sedated adult patients during 58% of ICU patient-days. Subjective scale
      based assessment-methods focused primarily on assessing excessive patient motion
      are currently used to assess the level of patient agitation, but are limited in
      their accuracy and resolution. This research quantifies this approach by
      developing an objective agitation measurement from patient motion that is sensed
      using digital video image processing. A fuzzy inference system (FIS) is developed
      to classify levels of motion that correlate with observed patient agitation,
      while accounting for motion due to medical staff working on the patient. Clinical
      tests for five ICU patients have been performed to verify the validity of this
      approach in comparison to agitation graded by nursing staff using the Riker
      Sedation-Agitation Scale (SAS). All trials were performed in the Christchurch
      Hospital Department of Intensive Care, with ethics approval from the Canterbury
      Ethics Committee. Results show good correlation with medical staff assessment
      with no false positive results during calm periods. Clinically, this initial
      agitation measurement method promises the ability to consistently and objectively
      quantify patient agitation to enable better management of sedation and agitation
      through optimised drug delivery leading to reduced length of stay and improved
      outcome.

PMID- 15451163
TI  - Three-dimensional reconstruction from serial sections in PC-Windows platform by
      using 3D_Viewer.
AB  - Three-dimensional (3D) reconstruction from serial sections allows identification
      of objects of interest in 3D and clarifies the relationship among these objects.
      3D_Viewer, developed in our laboratory for this purpose, has four major
      functions: image alignment, movie frame production, movie viewing, and shift
      overlay image generation. Color images captured from serial sections were
      aligned; then the contours of objects of interest were highlighted in a semi
      automatic manner. These 2D images were then automatically stacked at different
      viewing angles, and their composite images on a projected plane were recorded by
      an image transform-shift-overlay technique. These composition images are used in
      the object-rotation movie show. The design considerations of the program and the
      procedures used for 3D reconstruction from serial sections are described. This
      program, with a digital image-capture system, a semi-automatic contours highlight
      method, and an automatic image transform-shift-overlay technique, greatly speeds
      up the reconstruction process. Since images generated by 3D_Viewer are in a
      general graphic format, data sharing with others is easy. 3D_Viewer is written in
      MS Visual Basic 6, obtainable from our laboratory on request.

PMID- 15451164
TI  - VIVA (from virus variance), a library to reconstruct icosahedral viruses based on
      the variance of structural models.
AB  - VIVA is a software library that obtains low-resolution models of icosahedral
      viruses from projections observed at the electron microscope. VIVA works in a
      fully automatic way without any initial model. This feature eliminates the
      possibility of bias that could originate from the alignment of the projections to
      an external preliminary model. VIVA determines the viewing direction of the virus
      images by computation of sets of single particle reconstruction (SPR) followed by
      a variance analysis and classification of the 3D models. All structures are
      reduced in size to speed up computation. This limits the resolution of a VIVA
      reconstruction. The models obtained can be subsequently refined at best with use
      of standard libraries. Up today, VIVA has successfully solved the structure of
      all viruses tested, some of which being considered refractory particles. The VIVA
      library is written in 'C' language and is devised to run on widespread Linux
      computers.

PMID- 15451165
TI  - A SAS macro for the analysis of multivariate longitudinal binary outcomes.
AB  - Multiple binary outcomes occur quite frequently in oral health research, as well
      as other areas of health care research. When there is interest in comparing
      whether covariates influence one outcome more than another, statistical methods
      that adjust for the correlation that may exist between outcomes are warranted.
      Available software is limited to the extent that some pre-processing of the data
      is required. The main objective of this paper is to describe a SAS macro that can
      be used to estimate separate covariate effects on multiple, correlated binary
      outcomes. We demonstrate the utility of the macro by applying it to fit a
      trivariate logistic regression model using GEE where the three correlated
      longitudinal outcomes of interest include whether a subject had a problem
      oriented visit, a dental cleaning, or a routine check-up, or some combination
      thereof. All three outcomes were measured at four 6-monthly intervals (0-24
      months). Estimates from the trivariate logistic regression model are compared to
      results obtained by fitting three separate binary longitudinal models using GEE
      for each oral health outcome. The odds of having a problem-oriented visit were
      greater for males compared to females as estimated from the multivariate model (P
      = 0.0407), but the odds were not significant in the univariate model (P =
      0.0641). The multivariate model also aided in confirming expected results that
      consistent regular attenders (compared to consistent problem-oriented attenders)
      had greater odds of having received dental cleaning and check-ups relative to
      having problem-oriented visits (chi2 = 33.47, P < 0.01), and that those with
      broken teeth or broken filling (compared to those without) are at greater odds of
      having a problem-oriented visit relative to having dental cleaning or checkups
      (chi2 = 34.12, P < 0.01 and chi2 = 17.11, P < 0.01).

PMID- 15451166
TI  - Investigation of a new heart contractility power parameter.
AB  - First derivative of arterial blood pressure, dp/dt is known to reflect the
      contractility power of the heart. We hypothesize that the calculated area under
      each cardiac cycle of the blood pressure curve is also another practical tool in
      revealing the heart contractility power. Of the 84 subjects, 61 patients were
      found to have adequate contractility power (high dp/dt) and their mean area
      calculation resulted in 64.2 mmHg s with a standard deviation of 2.9 mmHg s. The
      remaining 23 patients have indicated poor heart contractility power (low dp/dt)
      and stayed in serious condition for long time. This group had mean area of 41.4
      +/- 3.1 mmHg s. Patients with poor contractility power had areas below 45 mmHg s,
      while all area calculations for patients with high contractility power stayed
      over 60 mmHg s. Therefore, small area of the arterial blood pressure curves seems
      to be a good indicator of a poor heart contractility power and the area
      calculation may be an adjunct parameter to the dp/dt that has been employed for
      the assessment of heart contractility.

PMID- 15451167
TI  - Structure and expression analysis of three subtypes of Arabidopsis MBF1 genes.
AB  - Multiprotein bridging factor 1 (MBF1) is a transcriptional co-activator that
      mediates transcriptional activation by bridging between an activator and a TATA
      box binding protein (TBP). Recently, we have reported that three Arabidopsis
      MBF1s play roles as transcriptional co-activators. This study shows that AtMBF1c
      is totally different from the other two in its structure and expression pattern,
      and that MBF1c genes also occur in other plant species, including monocots. We
      performed histochemical analysis of these genes using beta-glucuronidase (GUS)
      assays to characterize the expression profile of each AtMBF1 gene extensively. In
      pAtMBF1a Colon, two colons GUS transformants, GUS staining was observed only in
      anthers and seeds, whereas strong GUS activity in pAtMBF1b Colon, two colons GUS
      transformants was detected in leaf veins, stems, anthers, and seeds. In mature
      pAtMBF1c Colon, two colons GUS transformants, GUS staining was observed in almost
      all tissues. It is noteworthy that intense GUS staining was observed in anthers
      of all transformants. We also found that AtMBF1c expression was up-regulated upon
      diverse stress treatments including exposure to heat, hydrogen peroxide,
      dehydration, and high concentrations of salt. These findings suggest that AtMBF1c
      may be involved in stress response pathway.

PMID- 15451168
TI  - Gene structure and expression of the mouse APOBEC-1 complementation factor:
      multiple transcriptional initiation sites and a spliced variant with a premature
      stop translation codon.
AB  - Editing of apolipoprotein (apo) B mRNA is mediated by an enzyme-complex that
      consists of the catalytic cytidine deaminase APOBEC-1 and the mRNA binding
      protein APOBEC-1 complementation factor or APOBEC-1 stimulating protein
      (ACF/ASP). Here we describe the detailed characterization of the structure,
      expression and splicing pattern of the mouse ACF/ASP gene. ACF/ASP mRNA is mainly
      expressed in mouse liver, small intestine and kidney. The deduced protein
      sequences of ACF/ASP from mouse and man share an identity of 93%. The mouse
      ACF/ASP gene consists of 12 exons and gives rise predominantly to full-length
      transcripts. To a minor extent (<10%) ACF/ASP mRNA with unspliced exon 8 is
      generated in liver, kidney and small intestine that encodes a truncated protein
      with a predicted molecular weight of 43 kDa. The promoter of the mouse ACF/ASP
      gene lacks a canonical TATA-box, but contains a cluster of Sp1 binding sites and
      uses multiple transcriptional initiation sites. Transfection studies demonstrated
      a preference of this promoter for cell lines derived from the gastrointestinal
      tract and proved the location of the promoter core region. The high sequence
      identity between man and mouse-much higher as observed for APOBEC-1-indicates a
      strong evolutionary constraint on the structure-function relationship of ACF/ASP,
      most probably due to a central role in editing and processing of apo B mRNA.

PMID- 15451169
TI  - Genomic organization of the cadmium-inducible tandem repeat 25-kDa
      metallothionein of the oligochaete worm Enchytraeus buchholzi.
AB  - The terrestric oligochaete worm Enchytraeus buchholzi survives in cadmium (Cd)
      polluted environments by aid of its Cd-inducible 25 kDa cysteine-rich protein
      (CRP). Here, we analyze promoter and structure of the crp gene and compare its
      relationship to MT genes. The crp gene, approximately 12 kbp long, consists of 10
      exons with exons 2 to 9 encoding eight almost identical repeats of predominantly
      31 amino acids of the CRP. The introns of the crp gene contain various repetitive
      elements including retrotransposon-like sequences. The 683-bp promoter of the non
      constitutive crp gene exhibits a much higher basal activity than the mouse MT-II
      promoter in HepG2 cells. Essential for crp promoter activity is the distal region
      (-683/-521) with a GC box and the proximal region (-308/-8) with the four MREa,
      b, c, d and AP-1, -2, -3 elements, whereas the central portion (-521/-309) with
      CAAT box, CRE and a XRE causes promoter repression. The TATA box-, MREc- and the
      AP-2, -3-containing region are required for high crp promoter activity. Our data
      support the view that the crp gene is a unique MT-gene and has evolved by exon
      duplications from a MT-like ancestral gene.

PMID- 15451170
TI  - Proteasome inhibition alters the transcription of multiple yeast genes.
AB  - The 26S proteasome degrades denatured proteins and other proteins targeted for
      destruction by covalent modification. Here we show that impaired proteasome
      function influences the transcription of numerous yeast genes. Of 6144 genes
      present on the macroarray filters used in this study, approximately 5% showed
      measurable mRNA decreases and 2% showed mRNA increases following 30 min of
      proteasome inhibition. Northern blot hybridization shows that this response is
      time- and dose-dependent and occurs with either pharmacological or genetic
      impairment of the proteasome. A number of splicing factors possess the PEST motif
      found in certain proteasome substrates. However, mRNA levels drop with proteasome
      inhibition without obvious increases in intron-bearing pre-mRNA, indicating that
      splicing is not generally impaired when proteome activity is blocked. Chimeric
      gene constructs, nuclear run-on experiments, and transcriptional inhibition
      studies show that for members of three functional groups (i.e., ribosomal protein
      genes, histone genes, and heat shock protein genes) changes in mRNA levels occur
      largely by transcriptional modulation. In addition, these studies reveal a
      possible new means of modulating kinetochore levels through CEP3 expression.
      Together these data strongly support the view that proteasome activity plays a
      significant role in the regulation of eukaryotic gene expression.

PMID- 15451171
TI  - Transcriptional repression by the bHLH-Orange factor XHRT1 does not involve the C
      terminal YRPW motif.
AB  - Hairy-related transcription factors (HRTs) constitute a recently identified
      subfamily of basic-helix-loop-helix transcription factors containing an Orange
      domain (bHLH-O factors). As compared to the related HES proteins, HRTs exhibit
      distinct DNA-binding activities in vitro and the molecular mechanisms underlying
      their transcriptional activity remain poorly understood. We have identified here
      the sequence "ggCACGTGcc" as predominant binding site for Xenopus HRT1 (XHRT1).
      In transiently transfected 3T3 cells, XHRT1 represses the expression of a
      luciferase reporter gene under the control of multimerized XHRT1 binding sites.
      Deletion analysis indicated that repression by XHRT1 requires the presence of the
      DNA-binding bHLH motif and the Orange domain. However, the presence of the
      sequence motif YRPWGTEIGAF located at the very C-terminus of XHRT1 is
      dispensable. Accordingly, the groucho co-repressor, which is known to mediate
      transcriptional repression by HES factors through binding their C-terminal WRPW
      sequence, does not recognize the related YRPW motif present in the C-terminal
      part of XHRT1 significantly in vitro. As the C-terminus of HRTs is well
      conserved, our observation indicates that this part of HRTs, unlike the
      corresponding part of HES proteins, does not recruit the groucho co-repressor
      efficiently.

PMID- 15451172
TI  - Structural and functional characterization of the human SOX14 promoter.
AB  - SOX14 is a member of SOX gene family of putative transcriptional regulators. In
      this study we described the initial characterization of the human SOX14 gene
      promoter. The transcription start site was mapped by primer extension analysis.
      The minimal SOX14 promoter region that confers the basal promoter activity, as
      well as a proximal enhancer, was determined using promoter-reporter constructs.
      By mutational analysis we have shown that CCAAT box motif present in the SOX14
      promoter plays a functional role in the transcription of this gene.

PMID- 15451173
TI  - Cloning and expression of p-hydroxyphenylacetate 3-hydroxylase from Acinetobacter
      baumannii: evidence of the divergence of enzymes in the class of two-protein
      component aromatic hydroxylases.
AB  - The genes encoding for the reductase and oxygenase components of p
      hydroxyphenylacetate 3-hydroxylase from Acinetobacter baumannii were cloned and
      expressed in an E. coli system. The recombinant enzymes were purified and shown
      to have the same catalytic properties as the native enzyme. Sequence analysis and
      biochemical studies indicate that the enzyme represents a novel prototype of
      enzyme in the two-protein component class of aromatic hydroxylases. The C2
      component shows little similarity to other oxygenases in the same class,
      correlating with its uniquely broad flavin specificity. Analysis of the C1
      reductase sequence indicates that the binding sites of flavin and NADH mainly
      reside in the N-terminal half while the C-terminal half may be responsible for
      HPA-stimulation of NADH oxidation.

PMID- 15451174
TI  - Mechanism of viral persistence and resistance to nucleoside and nucleotide
      analogs in chronic hepatitis B virus infection.
AB  - Chronic Hepatitis B virus (HBV) infections remain a major problem public health
      problem worldwide, as well as a therapeutic challenge for clinicians. This review
      focuses on the main viral and host determinants involved in HBV persistence in
      infected cells. The mechanism of HBV resistance to nucleoside analogs are
      described as well as the concept for multiple drug therapy and combination with
      immunostimulatory approaches.

PMID- 15451175
TI  - Human herpesvirus 6 DNA polymerase: enzymatic parameters, sensitivity to
      ganciclovir and determination of the role of the A961V mutation in HHV-6
      ganciclovir resistance.
AB  - Human herpesvirus 6 (HHV-6) is latent in the majority of the adult population.
      Due to its ability of causing opportunistic infections, alone or in concert with
      the other beta-herpesviruses human cytomegalovirus (HCMV) and HHV-7, its
      importance as a pathogen in immunocompromised patients has increasingly been
      recognized. We here report the characterization of the main antiviral target, the
      HHV-6 DNA polymerase, expressed in a eukaryotic in vitro
      transcription/translation assay. This technique represents a fast and
      straightforward approach for the study of existing and new inhibitors of HHV-6
      DNA polymerase. The present study shows that ganciclovir is less active against
      HHV-6, as compared to its activity against HCMV, both in cell culture and at the
      enzymatic (i.e. DNA polymerase) level. Recently, a mutant HHV-6 strain carrying
      an amino acid substitution in the ganciclovir phosphorylating pU69 kinase has
      been isolated both from patients and in cell culture. The strain isolated in
      vitro, however, carried an additional mutation in the viral DNA polymerase. From
      our experiments presented here, we conclude that the pU69 M(318)V amino acid
      substitution rather than the A(961)V substitution in HHV-6 DNA polymerase, is
      responsible for the ganciclovir-resistant phenotype.

PMID- 15451176
TI  - Inactivation of adenovirus types 5 and 6 by Virkon S.
AB  - Throughout the pharmaceutical industry, adenovirus-based products are being
      developed for human use as vaccine vectors and gene therapy delivery vehicles.
      The implementation of effective decontamination procedures is critical to the
      successful manufacture of these products to minimize the risk of personnel
      exposure and prevent product cross-contamination in the manufacturing facility.
      In this investigation, we have conducted small-scale decontamination studies to
      determine the efficacy of Virkon S on the inactivation of adenovirus types 5 and
      6 in suspension. Virkon S is a commercially available oxidative disinfectant used
      against a variety of bacteria, spores, fungi, and viruses. A cytotoxicity-based
      endpoint dilution assay was used to quantify adenovirus potency before and after
      Virkon S treatment. We show that the level of organic content in the inactivation
      sample matrix has a significant impact on Virkon S activity. The potency of
      adenovirus types 5 and 6 was reduced by greater than six logs upon a five minute
      exposure to the appropriate concentration of Virkon S. Based on these results, we
      propose that Virkon S liquid decontamination procedures for adenovirus types 5
      and 6 use 0.9% Virkon S for contact times greater than five minutes.

PMID- 15451177
TI  - Inhibition of human immunodeficiency virus type I integrase by naphthamidines and
      2-aminobenzimidazoles.
AB  - Retroviral integrases catalyze two of the steps of insertion of proviral DNA into
      the host genomic DNA. Inhibitors that target the second step, strand transfer
      into the host DNA, have been demonstrated to have antiviral activity in cell
      culture. We describe two classes of HIV-1 integrase inhibitors that block strand
      transfer, one based on a naphthamidine core and one on a benzimidazole core.
      While the naphthamidine compounds showed some propensity to interact with the DNA
      substrate, both classes were shown to bind directly to integrase. The
      naphthamidine compounds showed activity in cell culture, and a direct effect on
      integrase was indicated by an increase in 2-LTR products in the presence of a
      naphthamidine compound. These two classes of compounds represent potential
      starting points for the development of new classes of integrase inhibitors.

PMID- 15451178
TI  - The prevalence and clinical characteristics of coinfection of SENV-H among
      Taiwanese chronic hepatitis C patients with combination therapy of high-dose
      interferon-alfa and ribavirin.
AB  - The clinical significance of coinfection of SENV-H among patients with chronic
      hepatitis C (CHC) and the response to combination therapy with high-dose
      interferon-alpha (IFN) plus ribavirin in Taiwan are uncertain. A total of 151
      (120 histologically proved) naive CHC patients who received 6 MU IFN thrice a
      week plus ribavirin for 24 weeks therapy were enrolled in this study. SENV-H DNA
      was tested by PCR method. Of 151 patients, 29 (19.2%) were positive for SENV-H
      DNA. The positive SENV-H DNA was significantly associated with HCV genotype 1b
      than non-1b infection (69.0% versus 43.4%; P = 0.011). No other clinical,
      histopathological and virological factor was related to positive SENV-H DNA.
      After combination therapy, the rate of sustained viral response (SVR) of HCV and
      SENV-H were 66.9 and 78.3%, respectively. By multivariate analyses, the
      significant factors associated with HCV SVR after combination therapy were HCV
      genotype non-1b, pretreatment HCV RNA levels less than 200,000 IU/mL, and younger
      age. We conclude that coexistent SENV-H infection, apparently associated with HCV
      genotype 1b, is found among 19.2% of Taiwanese CHC patients. Both HCV and SENV-H
      are highly susceptible to combination therapy with high dose IFN and ribavirin
      and SENV-H coinfection does not affect the HCV response.

PMID- 15451179
TI  - Mycophenolic acid inhibits avian reovirus replication.
AB  - Avian reoviruses (ARV) are economically important pathogens, especially in the
      poultry industry, where they cause viral arthritis and tenosynovitis.
      Mycophenolic acid (MPA) is an inhibitor of inosine monophosphate dehydrogenase
      (mainly used clinically for immunosuppression) that inhibits the replication of
      several viruses. We demonstrate in this study that MPA also is capable of
      inhibiting ARV replication in QM5 quail fibrosarcoma cells. The selectivity index
      of MPA in QM5 cells was determined as approximately 41. Concentrations of > or =3
      microg/ml MPA inhibited infectious ARV progeny production in QM5 cells by more
      than 100-fold. Inhibition of ARV replication also was seen in other cell lines,
      including HD-11 and Vero. Addition of exogenous guanosine to MPA-treated ARV
      infected QM5 cells restored viral replicative capacity to nearly normal levels.

PMID- 15451180
TI  - Lactoferrin inhibits human papillomavirus binding and uptake in vitro.
AB  - Lactoferrin (LF), a member of the transferrin family, is a bi-globular protein
      secreted in milk, saliva, tears, seminal fluid, endocervix and vaginal
      secretions. LF is an important player in the defence against pathogenic
      microorganisms and has also been shown to have activity against several viruses
      including herpesvirus, adenovirus, rotavirus and poliovirus. The antiviral
      activity of LF is directed against the early steps of viral infection and the LF
      antiviral effect against herpesvirus is mediated through LF binding to the
      herpesvirus receptor heparan sulfate. Human papillomavirus (HPV) causes genital
      warts and is a prerequisite for cervical cancer. HPV can also use heparan sulfate
      on the cell surface as a receptor. We studied the inhibition by LF on HPV entry
      by incubating HaCaT cells and HPV-16 virus-like particles (VLPs) with either
      human (HLF) or bovine lactoferrin (BLF). LF inhibited internalization of HPV-16
      particles using CFDA-SE-labelled VLPs that only fluoresce after internalisation.
      By using a western blot assay we also found dose-dependent LF inhibition of HPV
      16 VLP binding to the HaCaT cell surface. BLF was a more potent inhibitor of HPV
      entry than human LF. It was also clear that LF acted early in the HPV uptake
      process.

PMID- 15451181
TI  - Antiviral activity of diterpenes isolated from the Brazilian marine alga Dictyota
      menstrualis against human immunodeficiency virus type 1 (HIV-1).
AB  - The antiviral effect of the CH(2)Cl(2)/MeOH-soluble fraction from the alga
      Dictyota menstrualis on HIV-1 replication was evaluated in vitro. The
      antiretroviral activity was attributed to two diterpenes: (6R)-6-hydroxydichotoma
      3,14-diene-1,17-dial, named Da-1, and (6R)-6-acetoxi-dichotoma-3,14-diene-1,17
      dial, named AcDa-1. Da-1 or AcDa-1 were added to the culture medium of HIV-1
      infected PM-1 cells at different times post-infection or during virus
      adsorption/penetration. The results indicated that the compounds affected an
      early step of the virus replicative cycle. Virus binding and entry into the host
      cells were evaluated in the presence of each diterpene, but no inhibitory effect
      was observed. To evaluate provirus DNA synthesis/integration into the host
      genome, the viral protease coding sequence was amplified from total cellular DNA.
      Proviral DNA was not detected in infected cells incubated with the diterpenes. To
      investigate the effect of the diterpenes on the reverse transcription of the
      viral genomic RNA, the recombinant HIV-1 reverse transcriptase (RT) was assayed
      in vitro in the presence of each diterpene. Da-1 and AcDa-1 inhibited the RNA
      dependent DNA-polymerase activity of HIV-1 RT in a dose-dependent manner. Taken
      together, our results demonstrate that both diterpenes inhibit HIV-1 RT and
      consequently virus replication.

PMID- 15451182
TI  - Current status of antiviral therapy for juvenile-onset recurrent respiratory
      papillomatosis.
AB  - Human papillomavirus (HPV) infections are among the most prevalent of the
      sexually transmitted diseases, with up to 75% of women in the United States
      acquiring genital HPV infection at some point in their lives. HPV infections of
      the genital tract are of medical and public health concern due to their
      propensity to lead to the development of cervical cancer, and because they can be
      transmitted to the respiratory tract of a newborn child, resulting in juvenile
      onset recurrent respiratory papillomatosis (JO-RRP). JO-RRP is the second most
      common cause of hoarseness among pediatric patients, and is the most common
      benign neoplasm in the larynx. The traditional treatment for JO-RRP is the
      physical removal of the wart through laryngoscopy and surgical debulking of the
      airway papillomas. Papillomas frequently recur following surgical resection,
      however, often necessitating repeated ablative efforts to maintain a patent
      airway. In a minority of patients, surgical management must be supplemented with
      adjuvant medical therapy, with interferon being the best studied and most
      commonly utilized. Recently, a Phase II investigation of a therapeutic vaccine
      yielded promising results, and a Phase III evaluation of this therapeutic
      modality is planned. Other adjuvant treatments currently being utilized, but for
      which controlled data of benefit are lacking, include cidofovir, indole-3
      carbinol, ribavirin, mumps vaccine, and photodynamic therapy. As with surgical
      management, viral persistence occurs following treatment with these adjuvant
      modalities, further contributing to the challenge of managing patients with this
      potentially devastating disease.

PMID- 15451183
TI  - Apoptosis induced by a cytopathic hepatitis A virus is dependent on caspase
      activation following ribosomal RNA degradation but occurs in the absence of 2'-5'
      oligoadenylate synthetase.
AB  - We have presented previously evidence that the cytopathogenic 18f strain of
      hepatitis A virus (HAV) induced degradation of ribosomal RNA (rRNA) in infected
      cells [Arch. Virol. 148 (2003) 1275-1300]. In contrast, the non-cytopathogenic
      parent virus HM175 clone 1 had no effect on rRNA integrity. We present here data
      showing that rRNA degradation is followed by apoptosis accompanied by
      characteristic DNA laddering in the cytoplasm of 18f infected cells. The DNA
      laddering coincided with the detection of caspase 3 and PARP-1 cleavage and was
      dependent upon activation of the caspase pathway, since treatment with Z-VAD-FMK,
      a pan-caspase inhibitor, inhibited both events. RNase L mRNA was present in both
      virus-infected and uninfected cells. Messenger RNA for the interferon inducible
      enzyme 2'-5' oligoadenylate synthetase (2'-5' OAS), which polymerizes ATP into 2'
      5' oligo adenylate (2-5A, the activator of RNase L) in the presence of double
      stranded RNA, was not detected following virus infection. 2'-5' OAS mRNA was
      induced by treatment of the cells with interferon-beta (IFN-beta). IFN-beta mRNA
      was marginally induced following infection. However, phosphorylated STAT 1, a key
      regulator of interferon-stimulated gene transcription was not detected in virus
      infected cells. STAT 1 phosphorylation in response to IFN treatment was lower in
      virus-infected cells, compared to uninfected cells treated with interferon,
      suggesting that 18f virus infection interferes with interferon signaling. The
      results suggest that 18f infection causes the induction of a 2-5A independent
      RNase L like activity.

PMID- 15451184
TI  - Inhibition of bovine herpesvirus-4 replication in endothelial cells by arsenite.
AB  - The effect of arsenite pretreatment on bovine herpesvirus-4 (BHV-4) replication
      in bovine arterial endothelial (BAE) cells was studied. BHV-4 infectivity,
      including IE-2 expression, DNA replication and viral yield, were significantly
      reduced at nontoxic concentrations of arsenite in which cellular DNA synthesis or
      cell viability of BAE cells were not affected under resting and confluent
      conditions. This effect was accompanied by the induction of heat shock protein 70
      (HSP70) and an interrupted cell cycle (causing cell cultures to accumulate at the
      S and G2/M phases). Actinomycin D inhibited the induction of HSP70 and reduced
      arsenite antiviral activity. In conclusion, cellular stress response induced by
      arsenite in BAE cells inhibited replication of BHV-4, and probably resulted from
      the induction of HSP70 and interference of cell cycle progression.

PMID- 15451185
TI  - In vitro generation and characterisation of an influenza B variant with reduced
      sensitivity to neuraminidase inhibitors.
AB  - A contemporary influenza type B virus was passaged in vitro in the presence of
      increasing concentrations of the neuraminidase inhibitors, zanamivir and
      oseltamivir carboxylate (0.1-1000 microM over nine passages). After the fifth
      passage in the presence of zanamivir (10 microM), the virus acquired a Glu 119
      Asp neuraminidase mutation (influenza A N2 subtype numbering) in the enzyme
      active site. After a further three passages, in which growth occurred in 100
      microM of zanamivir, a Gln 218 Lys mutation (A (H3) numbering) in the HA1 domain
      of the haemagglutinin was found. In a fluorescence-based neuraminidase inhibition
      assay, viruses with the Glu 119 Asp NA mutation had a 32,000-fold reduction in
      sensitivity to the NA inhibitor zanamivir compared to the wild-type virus, while
      the mutation resulted in a 105-fold reduction in sensitivity to oseltamivir
      carboxylate. Viruses grown in the presence of 1000 microM oseltamivir carboxylate
      did not acquire any neuraminidase mutations but did have a His 103 Gln
      substitution (A (H3) numbering) in the HA1 region of the haemagglutinin which was
      demonstrated to significantly reduce receptor binding strength in vitro. Tissue
      culture assays demonstrated that the HA mutation caused a seven-fold reduction in
      sensitivity to oseltamivir carboxylate, and a 90-fold reduction in sensitivity to
      zanamivir.

PMID- 15451186
TI  - Structure of polysaccharide from Polygonatum cyrtonema Hua and the antiherpetic
      activity of its hydrolyzed fragments.
AB  - A neutral polysaccharide named PD was isolated from the traditional Chinese
      medicinal herb, Polygonatum cyrtonema Hua. Five fragments were isolated by Bio
      Gel P4 chromatography from hydrolysates of PD. Using assays of cytopathic effect
      inhibition, neutral red dye uptake and plaque forming inhibition, it was proved
      that the fragments with degree of polymerization (DP) of 4 and 5 were the
      shortest ones which retained the activity against herpes simplex virus type 2
      (HSV-2) in vero cell culture. The structures of PD and one of its activity
      retaining fragments, B3, were determined by permethylation followed with
      reductive cleavage, mass spectrometry and nuclear magnetic resonance
      spectrometry. It was shown that PD was a branched fructan with average DP of 28.
      There was one two-residue side chain composed of (2 --> 6)-linked beta-d
      fructofuranosyl (Fruf) residues every three (2 --> 1)-linked beta-d-Fruf residues
      in the backbone of PD, whereas B3 was a mixture containing 1-kestose and
      neokestose series of oligosaccharides of DP 3-5 without branches.

PMID- 15451187
TI  - Experimental infection of humans with A2 respiratory syncytial virus.
AB  - Development of a readily available challenge model of human respiratory syncytial
      virus (RSV) infection would be a useful tool for evaluation of antiviral agents
      and vaccine candidates. Accordingly, we evaluated a new challenge pool of RSV A2
      virus, provided by the National Institutes of Allergy and Infectious Diseases.
      Healthy adults subjects were inoculated intranasally with various dilutions of
      the pool, and virus shedding, clinical symptoms, and immune response were
      studied. In a preliminary study of 36 randomly selected volunteers, stratified by
      serum neutralization titer both higher inoculum dose (4.7 log(10) TCID(50) virus)
      and lower antibody titer (<==10.36 log(2)), were associated with infection. In a
      second confirmatory study 12 of 13 (92%) subjects selected for low serum
      neutralizing activity shed virus after challenge with the high inoculum of virus.
      Mean peak virus shedding was 2.2 log(10) TCID(50)/mL nasal wash with a mean
      duration of 4 days. None of the subjects developed signs or symptoms of lower
      airway disease, although respiratory symptom scores and nasal mucus weight were
      temporally correlated with virus shedding. Prescreening for low levels of
      neutralizing antibody may allow selection of subjects with relatively higher
      susceptibility to experimental infections. This model provides a safe and
      efficient mechanism for proof-of-concept studies of anti-viral agents and RSV
      vaccines, as well as for investigation of immune responses to infection.

PMID- 15451188
TI  - Inhibition of cytomegalovirus infection by lactoferrin in vitro and in vivo.
AB  - Lactoferrin is an antimicrobial agent, that, amongst other viruses, inhibits
      cytomegalovirus (CMV). In this study, we addressed the mechanism(s) by which
      lactoferrin interacts with CMV and its target cells to inhibit infection. We also
      studied the antiviral activity of lactoferrin in vivo in rat CMV models with and
      without immune suppression. We cationized a protein of similar molecular weight,
      i.e. human serum albumin (HSA), as well as a protein with a smaller molecular
      weight (beta-lactoglobulin). While HSA itself displayed no anti-CMV activity in
      vitro, cationic HSA inhibited CMV replication to a similar extent as lactoferrin.
      Time-of-addition assays indicated that all cationic proteins interacted with an
      early event in the infection and pre-incubation of cells rather than of virus
      significantly reduced CMV replication. Rats were treated with lactoferrin (4, 40
      or 160 mg/kg, intravenously), beginning at 6h after CMV administration.
      Subsequently, the rats were treated three times a week. As a positive control,
      CMV-infected rats were treated with cidofovir, and this agent proved to be highly
      active in the rat models for CMV. Treatment with lactoferrin was beneficial when
      infection was initiated with cell-free virus, but not with virus-infected
      leukocytes. Lactoferrin treatment led to a 10-fold reduction in the final virus
      titers (salivary glands) at 4 weeks after infection in the immunocompromised
      rats. Lactoferrin exerted its effects via inhibition of cell entry rather than
      via stimulation of the immune system.

PMID- 15451189
TI  - Application of real-time PCR for testing antiviral compounds against Lassa virus,
      SARS coronavirus and Ebola virus in vitro.
AB  - This report describes the application of real-time PCR for testing antivirals
      against highly pathogenic viruses such as Lassa virus, SARS coronavirus and Ebola
      virus. The test combines classical cell culture with a quantitative real-time PCR
      read-out. The assay for Lassa virus was validated with ribavirin, which showed an
      IC(50) of 9 micrograms/ml. Small-scale screening identified a class of imidazole
      nucleoside/nucleotide analogues with antiviral activity against Lassa virus. The
      analogues contained either dinitrile or diester groups at the imidazole 4,5
      positions, and many of which possessed an acyclic sugar or sugar phosphonate
      moiety at the imidazole 1-position. The IC(50) values of the most active
      compounds ranged from 5 to 21 micrograms/ml. The compounds also inhibited
      replication of SARS coronavirus and Ebola virus in analogous assays, although to
      a lesser extent than Lassa virus.

PMID- 15451190
TI  - Evidence for the functional activity of hypoxia-inducible transcription factors
      overexpressed in preeclamptic placentae.
AB  - Placentas from women with preeclampsia overexpress the hypoxia-inducible
      transcription factor proteins, HIF-1alpha and -2alpha (Rajakumar 2001, Biol
      Reprod 64; p499-506 and p1019-1020). As a first step in evaluating whether HIF
      alpha overexpressed in preeclamptic placentae is capable of transactivation, we
      tested its ability to bind to the DNA hypoxia response element (HRE). Six pairs
      of normal and preeclamptic placentae obtained by cesarean section were
      investigated. Three biopsy sites per placenta were analyzed. We first confirmed
      HIF-1alpha protein overexpression in the preeclamptic placentae using Western
      analysis. The ratios of the arbitrary densitometry units for HIF-1alpha protein
      from the preeclamptic and normal placentae (PE/NP) in the three biopsy sites
      were: 1.9 +/- 0.3, 1.7 +/- 0.2 and 1.8 +/- 0.2, each p < 0.05 vs 1.0. (A ratio of
      >1.0 indicates that HIF-1alpha protein expression in placentas of women with PE
      exceeds that in placentas of NP women.) Conventional methods for extracting
      nuclear proteins and subsequent analysis by electrophoretic mobility shift assay
      were not suited for the frozen, archived samples (data not shown). Therefore, we
      employed DNA affinity chromatography using a biotinylated oligonucleotide
      representing the HRE of the erythropoietin gene coupled to streptavidin-coated
      Dynabeads. The HRE-bound proteins were then characterized by Western blot
      analysis. The PE/NP ratios of HRE-bound HIF-1alpha in the three biopsy sites from
      the six pairs of normal and preeclamptic placentae were 1.7 +/- 0.2, 2.1 +/- 0.4
      and 2.4 +/- 0.5, each p < 0.05 vs 1.0. Having established DNA-binding potential
      at least in vitro, we subsequently analyzed three proteins that have been shown
      to be regulated by HIF-alpha as downstream, molecular markers of HIF-1alpha
      activity in vivo. VEGF receptor Flt-1 and Flk-1 play key roles in angiogenesis.
      Tyrosine hydroxylase is the rate-limiting enzyme in catecholamine synthesis. All
      three genes contain functional HRE in their promoter sequences. Total proteins
      were extracted from the same biopsy samples that were used for total and HRE
      bound HIF-1alpha. Using specific antibodies we performed Western analysis and the
      levels of these three proteins were quantitated. The Flt-1 and tyrosine
      hydroxylase proteins were significantly higher, and Flk-1 significantly lower in
      placentae from preeclamptic compared to normal pregnancies. In summary, HIF
      1alpha protein overexpressed in preeclamptic placentae is capable of binding to
      its DNA recognition sequence in vitro, and modulates gene expression in vivo.

PMID- 15451191
TI  - Expression pattern of collagen XVIII and its cleavage product, the angiogenesis
      inhibitor endostatin, at the fetal-maternal interface.
AB  - Endostatin, the C-terminal fragment of the basement membrane protein collagen
      XVIII regulates epithelial cell migration and impairs tumour growth by inhibiting
      angiogenesis. Here, we investigated the expression pattern of collagen
      XVIII/endostatin in human placental and decidual tissues of various ages of
      gestation as well as in primary villous cytotrophoblasts, trophoblast cell lines,
      and villous explant cultures differentiating along the invasive pathway. RT-PCR
      analysis revealed production of collagen XVIII mRNA in total placenta and decidua
      of early and late pregnancy and in SGHPL-5 and HTR-8/Svneo cells. Collagen XVIII
      transcripts were absent from purified extravillous trophoblasts and
      syncytialising trophoblast cultures. Accordingly, an antibody against a protein
      domain common to different collagen XVIII isoforms detected the 180 kDa protein
      in villous and decidual tissue and cultivated placental fibroblasts but not in
      the different isolated trophoblast cell types. Immunohistochemical analyses
      localised collagen XVIII to villous basement membranes and to the endothelium as
      well as to placental and decidual stromal cells. Interestingly, expression of
      various forms of endostatin (20 and 26 kDa) was detected in placenta and decidua
      using Western blot analyses. Moreover, supplementation of recombinant endostatin
      increased MMP-2 expression in villous explant cultures and SGHPL-5 cells
      suggesting that the inhibitor may modulate extravillous trophoblast
      differentiation.

PMID- 15451192
TI  - Effect of betamethasone administration to the pregnant baboon at 0.75 gestation
      on placental eNOS distribution and activity.
AB  - Betamethasone is frequently administered to pregnant women at risk of premature
      labor to accelerate fetal lung maturation. Maternally administered betamethasone
      produces pronounced changes in the fetal peripheral vasculature, raises fetal
      blood pressure and produces fetal growth restriction. Endothelial nitric oxide
      synthase (eNOS) plays an important role in regulating vascular tone. We
      hypothesized that effects of betamethasone on the fetal vasculature include
      decreased eNOS activity. We determined a significant depression of total
      placental eNOS protein measured by ELISA (betamethasone treated vs control, 0.48
      +/- 0.28 vs 1.57 +/- 0.45, p < 0.05) and immunohistochemistry in both
      syncytiotrophoblast and vascular endothelium. Following betamethasone exposure,
      eNOS mRNA and enzyme activity showed decreasing trends which were not
      statistically significant. eNOS protein was higher in the placentas of both
      control and betamethasone treated baboons in the presence of a female fetus
      compared with a male fetus. The same effect of the sex of the fetus was observed
      in the betamethasone group for eNOS mRNA. In conclusion, maternally administered
      betamethasone produces a consistent decrease in several indices of placental eNOS
      function that may play a role in the altered cardiovascular dynamics and fetal
      growth retardation produced by betamethasone administration in late pregnancy.

PMID- 15451193
TI  - Fetal vasculitis in preterm newborns: interrelationships, modifiers, and
      antecedents.
AB  - Histologic expressions of the fetal inflammatory response predict preterm
      delivery and neonatal disorders. We examined 1146 placentas in the Developmental
      Epidemiology Network data set for histologic evidence of membrane inflammation
      (subchorionitis, chorionitis, and chorioamnionitis) and fetal vasculitis (acute
      umbilical vasculitis or chorionic vasculitis). Our main findings are that (1) in
      the presence of membrane inflammation, fetal vasculitis is common, (2) duration
      of membrane rupture and gestational age appear to modify the risk of fetal
      vasculitis, (3) this risk modification differs for the different components of
      fetal vasculitis, i.e. umbilical and chorionic vasculitis, and (4) antecedents
      can be identified that appear to increase or decrease the risk of fetal
      vasculitis among births with membrane inflammation. We conclude that fetal
      vasculitis, the morphologic component of the fetal inflammatory response, might
      not be a homogeneous entity and deserves further study.

PMID- 15451194
TI  - Galectin-1 and galectin-3 in the trophoblast of the gestational trophoblastic
      disease.
AB  - While the presence and distribution of galectin-1 and galectin-3 in different
      normal trophoblast cell populations is known, no information is available
      regarding their occurrence in malignant trophoblast of gestational trophoblastic
      disease (GTD). Galectins-1 and -3 have, however, been implicated in malignancies
      of other tissues. Immunoreactivity for these galectins in the transformed
      trophoblast of invasive mole (n = 8), choriocarcinoma (n = 7) and one case of
      placental site trophoblastic tumor (PSTT) was compared to that of the invasive
      trophoblast of the normal first trimester of pregnancy implantation sites (n =
      9). A large proportion of the transformed trophoblast cells of all GTD studied
      were positive for galectin-1 and galectin-3. Immunoreactivity was scored
      semiquantitatively to include both the prevalence among the trophoblast cells and
      the intensity of staining. Immunoreactivity for both galectin-1 and galectin-3 in
      gestational trophoblastic disease is increased (significant differences at p <
      0.05, Mann-Whitney Rank Sum Test). This finding may suggest a possible
      implication of galectins-1 and -3 in the invasiveness of the transformed
      trophoblastic cell, although the exact physiological significance of this finding
      remains to be determined.

PMID- 15451195
TI  - Placenta and fetal membranes of the four-toed elephant shrew, Petrodromus
      tetradactylus.
AB  - The four-toed elephant shrew is the only extant member of the genus Petrodromus.
      Some features of its placentation are found in other elephant shrews and may be
      important in consolidating the elephant shrews in the order Macroscelidea. These
      include implantation in an embryo chamber at the caudal end of the uterine horn;
      a large yolk sac; a large, lobulated allantoic sac; a distinct layer of
      proliferative trophoblastic cells between the labyrinthine and spongy zones of
      the placenta; an accessory epitheliochorial placenta; and the formation of a
      mesoplacenta by the decidua basalis. Of particular note are the large granulated
      cells that occupy the walls of decidual, myometrial and mesometrial arteries.
      They appear to be uterine natural killer cells. The persistence of a relatively
      large yolk sac and a large lobulated allantoic sac is a feature which Petrodromus
      and other elephant shrews share with other members of the superordinal clade
      Afrotheria.

PMID- 15451196
TI  - Expression and localization of matrix metalloproteinases (MT1-MMP, MMP-2) and
      tissue inhibitor of metalloproteinase-2 (TIMP-2) during synepitheliochorial
      placentation of goats (Capra hircus).
AB  - Matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases
      (TIMPs) play key roles during the placentation of highly invasive haemochorial
      type. Our knowledge is yet scanty, however, regarding the roles played by MMPs
      and TIMPs in the placentation of non-invasive synepitheliochorial type. In the
      present study, expression patterns of MT1-MMP, MMP-2 and TIMP-2 mRNAs as well as
      the encoded proteins in the endometrium and the placenta were examined on Days
      35, 75, and 100 of pregnancy, representing roughly the 1st, 2nd and 3rd
      trimesters of caprine gestation, by means of quantitative RT-PCR analysis, in
      situ hybridization, immunoblotting, gelatin zymography and immunohistochemistry.
      In the endometrium and the intercotyledonal trophoblast, the expression levels of
      the 3 genes remained relatively uniform throughout the period of gestation
      examined. Curiously, however, in the placentomes, the relative expression levels
      of MT1-MMP mRNA increased linearly from Day 35 to Day 100, while those of MMP-2
      and TIMP-2 were clearly down-regulated in Day 100 placentae. The expression
      levels of MT1-MMP and TIMP-2 proteins in placentomes were well correlated with
      those of the respective mRNAs. In the case of MMP-2, the total amount of MMP-2
      protein (the combined values of the latent, the intermediate and the active
      forms) decreased slightly, while the levels of the active form increased markedly
      from Day 35 to Day 100. Immunohistochemical analysis of the placentome revealed
      that MT1-MMP and TIMP-2 proteins were co-localized in the binucleate trophoblast
      cells; expression of these 2 proteins was not detected in the uninuclear
      principal trophoblast cells. MMP-2 expression was detected both in the binucleate
      and in the uninuclear principal cells of the trophoblast and in the endometrial
      stromal cells of the uterine septum, regardless of the stages of gestation
      examined. The co-localization of MT1-MMP, MMP-2 and TIMP-2 in binucleate
      trophoblast cells, the cotyledonal trophoblast cells and the subsyncytial stromal
      cells is likely to reflect the functional coordination of the 3 proteins in these
      cells during trophoblastic invasion and the placental tissue remodeling in the
      placentome.

PMID- 15451197
TI  - Structure and glycosylation of the term yolk sac placenta and uterine attachment
      site in the viviparous shark Mustelus canis.
AB  - The viviparous shark Mustelus canis nurtures its young within the uterus by means
      of a modified yolk sac which functions as a placenta. Two term specimens have
      been examined with a panel of 21 biotinylated lectins to assess whether glycans
      form a prominent interface between fetal and maternal tissues as in their therian
      counterparts. The yolk sac placenta was lined by a thin egg envelope which
      apposed though did not make contact with the uterine epithelium, and expressed
      fucosyl, N-acetyl glucosamine/lactosamine residues and some complex N-glycan,
      while the attached, thin ectoderm cells stained selectively with lectins from
      Anguilla anguilla and Arachis hypogaea indicating fucosyl and beta-galactosyl
      residues; other lectins bound to a variable degree. Large yolk sac endoderm cells
      were heavily glycosylated and expressed a wide range of glycans. The apposing
      uterine epithelium had two epithelial layers with distinctive patterns of
      glycosylation, the apical layer stained strongly with Anguilla anguilla lectin
      and the basal cells with lectins from Wisteria floribunda and Helix pomatia, the
      latter indicating plentiful N-acetyl galactosamine though both layers stained
      variably with other lectins also. A population of sparse, large, globular cells
      expressed alpha2,3-linked sialic acid and N-acetyl glucosamine oligomers. Fetal
      and maternal vessels were heavily glycosylated as in their therian counterparts.
      These data indicate a prominent role for glycans at the fetomaternal interface of
      these chondrichthyan fishes.

PMID- 15451198
TI  - Morphometric evidence that villous development and fetoplacental angiogenesis are
      compromised by intrauterine growth restriction but not by pre-eclampsia.
AB  - The aim of this study was to compare morphometric measures of villous
      development, villous capillarization, fetoplacental angiogenesis and capillary
      lumen remodelling in normal pregnancies with those complicated by intrauterine
      growth restriction (IUGR) with and without preeclampsia (PE). To this end, term
      placentas from control pregnancies (n = 9) and cases of IUGR alone (n = 5), PE
      alone (n = 5) and IUGR with PE (n = 5) provided random samples of tissue. These
      were fixed in formalin and Masson trichrome-stained wax sections were analysed
      stereologically. Overall growth of peripheral villi and fetal capillaries was
      assessed by estimating total volumes, surface areas and lengths. Villous
      capillarization was monitored using volume, surface and length densities and
      capillary:villus surface and length ratios. Measures of villous maturation and
      capillary lumen remodelling comprised mean cross-sectional areas, perimeters and
      shapes (perimeter(2)/area). Between-group comparisons were drawn using two-way
      analysis of variance. IUGR was associated with abnormal growth of villi and fetal
      capillaries. Reduced villous growth was not accompanied by changes in measures of
      villous capillarization or maturation and reduced capillary growth was not
      accompanied by changes in lumen calibre or shape. In contrast, PE was not
      associated with any main or interaction effects on placental morphometry. It is
      concluded that IUGR, but not PE, is associated with impoverished villous
      development and fetoplacental angiogenesis. The latter is due to production of
      fewer and/or shorter capillary segments (rather than a decrease in capillary
      calibre), does not affect villous capillarization and is not accompanied by
      luminal remodelling.

PMID- 15451199
TI  - Hemodynamical changes on the maternal side of the placental circulation in normal
      and complicated pregnancies.

PMID- 15451200
TI  - Keep genome data freely accessible.

PMID- 15451201
TI  - Is that it, then, for blockbuster drugs?

PMID- 15451202
TI  - Pushing the imatinib envelope.

PMID- 15451203
TI  - Nurture versus nature: evidence of intrauterine effects on suicidal behaviour.

PMID- 15451204
TI  - Oral antibiotics for the treatment of severe pneumonia in children.

PMID- 15451205
TI  - Parkinson's disease and dementia with Lewy bodies: a difference in dose?

PMID- 15451206
TI  - A race to the death: British American Tobacco and the Chinese Grand Prix.

PMID- 15451207
TI  - Misinterpretation of numbers: a potential source of physician's error.

PMID- 15451208
TI  - Three meetings and fewer funerals--misoprostol in postpartum haemorrhage.

PMID- 15451209
TI  - What should the burden of proof be for acceptance of a new breast-cancer
      screening technique?

PMID- 15451210
TI  - Why are 4 million newborn babies dying every year?

PMID- 15451211
TI  - All children have a right to full access to treatment for cancer.

PMID- 15451212
TI  - ACST: which subgroups will benefit most from carotid endarterectomy?

PMID- 15451213
TI  - ACST: which subgroups will benefit most from carotid endarterectomy?

PMID- 15451214
TI  - ACST: which subgroups will benefit most from carotid endarterectomy?

PMID- 15451215
TI  - ACST: which subgroups will benefit most from carotid endarterectomy?

PMID- 15451217
TI  - ACST: which subgroups will benefit most from carotid endarterectomy?

PMID- 15451218
TI  - This is the first study.

PMID- 15451219
TI  - Progression-free survival in gastrointestinal stromal tumours with high-dose
      imatinib: randomised trial.
AB  - BACKGROUND: Imatinib is approved worldwide for use in gastrointestinal stromal
      tumours (GIST). We aimed to assess dose dependency of response and progression
      free survival with imatinib for metastatic GIST. METHODS: 946 patients were
      randomly allocated imatinib 400 mg either once or twice a day. Those assigned the
      once a day regimen who had progression were offered the option of crossover. The
      primary endpoint was progression-free survival. Analysis was by intention to
      treat. FINDINGS: At median follow-up of 760 days (IQR 644-859), 263 (56%) of 473
      patients allocated imatinib once a day had progressed compared with 235 (50%) of
      473 who were assigned treatment twice a day (estimated hazard ratio 0.82 [95% CI
      0.69-0.98]; p=0.026). Side-effects arose in 465/470 (99%) patients allocated the
      once daily regimen compared with 468/472 (99%) assigned treatment twice a day. By
      comparison with the group treated once a day, more dose reductions (77 [16%] vs
      282 [60%]) and treatment interruptions (189 [40%] vs 302 [64%]) were recorded in
      patients allocated the twice daily regimen, but treatment in both arms was fairly
      well tolerated. 52 (5%) patients achieved a complete response, 442 (47%) a
      partial response, and 300 (32%) stable disease, with no difference between
      groups. Median time to best response was 107 days (IQR 58-172). INTERPRETATION:
      If response induction is the only aim of treatment, a daily dose of 400 mg of
      imatinib is sufficient; however, a dose of 400 mg twice a day achieves
      significantly longer progression-free survival.

PMID- 15451220
TI  - Restricted fetal growth and adverse maternal psychosocial and socioeconomic
      conditions as risk factors for suicidal behaviour of offspring: a cohort study.
AB  - BACKGROUND: Until now, sparse and contradictory results about an association
      between adverse neonatal, obstetric, and maternal conditions and heightened
      suicide risk in adolescents have been reported. The aims of this study were to
      investigate the relations between fetal growth, obstetric complications, and the
      mother's psychosocial and socioeconomic situation and the risk in early adulthood
      of suicide and attempted suicide in the offspring. METHODS: Obstetric, neonatal,
      and maternal risk factors for suicide and attempted suicide in 713370 young
      adults, born in Sweden between 1973 and 1980, who were followed-up until Dec 31,
      1999, were examined by data linkage between Swedish registers. Univariate and
      multivariate hazard ratios, derived from proportional-hazard models, were
      estimated. FINDINGS: Significantly raised risk of attempted suicide was reported
      for individuals of short birth length, adjusted for gestational age (hazard ratio
      1.29, 95% CI 1.18-1.41, p<0.0001); born fourth or more in birth order (1.79, 1.62
      1.97, p<0.0001); born to mothers with a low educational level (1.36, 1.27-1.46,
      p<0.0001) (attributable proportion 10.3%); and those who, at time of delivery,
      had mothers aged 19 years or younger (2.09, 1.89-2.32, p<0.0001). Significant
      predictors of suicide were low birthweight, adjusted for gestational age (2.23,
      1.43-3.46, p<0.0001), and teenage motherhood (2.30, 1.64-3.22, p<0.0001).
      INTERPRETATION: Multiparity and low maternal education predicted suicide attempt,
      whereas restricted fetal growth and teenage motherhood were associated with both
      suicide completion and attempt in offspring.

PMID- 15451221
TI  - Oral amoxicillin versus injectable penicillin for severe pneumonia in children
      aged 3 to 59 months: a randomised multicentre equivalency study.
AB  - BACKGROUND: Injectable penicillin is the recommended treatment for WHO-defined
      severe pneumonia (lower chest indrawing). If oral amoxicillin proves equally
      effective, it could reduce referral, admission, and treatment costs. We aimed to
      determine whether oral amoxicillin and parenteral penicillin were equivalent in
      the treatment of severe pneumonia in children aged 3-59 months. METHODS: This
      multicentre, randomised, open-label equivalency study was undertaken at tertiary
      care centres in eight developing countries in Africa, Asia, and South America.
      Children aged 3-59 months with severe pneumonia were admitted for 48 h and, if
      symptoms improved, were discharged with a 5-day course of oral amoxicillin. 1702
      children were randomly allocated to receive either oral amoxicillin (n=857) or
      parenteral penicillin (n=845) for 48 h. Follow-up assessments were done at 5 and
      14 days after enrollment. Primary outcome was treatment failure (persistence of
      lower chest indrawing or new danger signs) at 48 h. Analyses were by intention-to
      treat and per protocol. FINDINGS: Treatment failure was 19% in each group (161
      patients, pencillin; 167 amoxillin; risk difference -0.4%; 95% CI -4.2 to 3.3) at
      48 h. Infancy (age 3-11 months; odds ratio 2.72, 95% CI 1.95 to 3.79), very fast
      breathing (1.94, 1.42 to 2.65), and hypoxia (1.95, 1.34 to 2.82) at baseline
      predicted treatment failure by multivariate analysis. INTERPRETATION: Injectable
      penicillin and oral amoxicillin are equivalent for severe pneumonia treatment in
      controlled settings. Potential benefits of oral treatment include decreases in
      (1) risk of needle-borne infections; (2) need for referral or admission; (3)
      administration costs; and (4) costs to the family.

PMID- 15451222
TI  - Intravenous immunoglobulin in secondary progressive multiple sclerosis:
      randomised placebo-controlled trial.
AB  - BACKGROUND: Several double-blind placebo-controlled trials of relapsing-remitting
      multiple sclerosis have shown beneficial effects of intravenous immunoglobulin
      (IVIG) on relapse rate and disability. The European Study on Intravenous
      Immunoglobulin in Multiple Sclerosis set out to test IVIG in the secondary
      progressive phase of the disease. METHODS: 318 patients with clinically definite
      secondary progressive multiple sclerosis (mean age 44 years [SD 7]) were randomly
      assigned IVIG 1 g/kg per month (n=159) or an equivalent volume of placebo
      (albumin 0.1%; n=159) for 27 months. After baseline investigation, clinical
      assessments were made every 3 months and MRI was repeated after 12 months and 24
      months. The primary outcome was confirmed worsening of disability as defined by
      the time to first confirmed progression on the expanded disability status scale
      (EDSS). Analyses were by intention to treat. FINDINGS: 19 patients in the IVIG
      group and 39 in the placebo group terminated study treatment prematurely but were
      included in the analyses. IVIG treatment had no beneficial effect on time to
      confirmed EDSS progression (hazard ratio 1.11 [95% CI 0.80-1.53] for IVIG versus
      placebo). The annual relapse rate was 0.46 in both groups. No significant
      differences between the treatment groups were found in any of the other clinical
      outcome measures or in the change of T2-lesion load over time. The treatment was
      generally well tolerated, although deep venous thrombosis, pulmonary embolism, or
      both occurred in seven patients with risk factors for thromboembolism (IVIG six,
      placebo one). INTERPRETATION: Treatment with IVIG in this study did not show any
      clinical benefit and therefore cannot be recommended for patients with secondary
      progressive multiple sclerosis.

PMID- 15451223
TI  - Evidence against a role for SV40 infection in human mesotheliomas and high risk
      of false-positive PCR results owing to presence of SV40 sequences in common
      laboratory plasmids.
AB  - BACKGROUND: PCR-based evidence of infection by simian virus 40 (SV40) has been
      reported in varying proportions of pleural mesotheliomas and other tumours, but
      data are conflicting and reproducibility limited. During a study of SV40 in
      relation to homozygous deletion of CDKN2A in mesotheliomas, we became concerned
      by inconsistent results and therefore used several independent techniques to
      investigate SV40 in these tumours. METHODS: High-quality DNA and RNA were
      extracted from 71 frozen mesothelioma samples. DNA PCR was done with four sets of
      primers for the SV40 T-antigen gene. RNA transcripts were examined by RT-PCR.
      FINDINGS: The first two primer sets for DNA PCR gave positive results in
      proportions similar to those reported in positive studies (56-62%) but there were
      unusual reproducibility difficulties. These primers were in a region of the T
      antigen gene (nucleotides 4100-4713) that is present in many common laboratory
      plasmids. In assays with PCR primers not included within that region, only four
      cases (6%) showed products but these were too faint to suggest clonal infection.
      Further PCR assays confirmed that the SV40 sequences in the tumour samples had a
      deletion found only in plasmids, not in native functional SV40. Review of
      previous studies showed a similar pattern of discrepancies between SV40 T-antigen
      DNA PCR results obtained with primers within and beyond the region 4100-4713. All
      71 mesotheliomas were negative for T-antigen transcripts by RT-PCR, and lacked T
      antigen-positive tumour cells by immunohistochemistry. INTERPRETATION: Our data
      based on three independent experimental approaches do not support a significant
      role for SV40 in human mesotheliomas. The risk of false-positive results due to
      contamination by common laboratory plasmids containing SV40 sequences has been
      underestimated. Studies of SV40 based on PCR methods require careful primer
      design to reduce this risk. RELEVANCE TO PRACTICE: This paper presents several
      lines of evidence against the proposed link between SV40 infection and human
      mesotheliomas. Studies reporting a high prevalence of SV40 DNA in human tumours
      have been based on molecular assays prone to false-positive results. Because SV40
      appears unlikely to have a major role, if any, in human mesotheliomas, clinicians
      should continue to consider asbestos exposure as the most likely and most
      thoroughly established aetiological factor in individuals with this cancer.

PMID- 15451224
TI  - Alpha-synuclein locus duplication as a cause of familial Parkinson's disease.
AB  - Genomic triplication of the alpha-synuclein gene (SNCA) has been reported to
      cause hereditary early-onset parkinsonism with dementia. These findings prompted
      us to screen for multiplication of the SNCA locus in nine families in whom
      parkinsonism segregates as an autosomal dominant trait. One kindred was
      identified with SNCA duplication by semiquantitative PCR and confirmed by
      fluorescent in-situ hybridisation analysis in peripheral leucocytes. By contrast
      with SNCA triplication families, the clinical phenotype of SNCA duplication
      closely resembles idiopathic Parkinson's disease, which has a late age-of-onset,
      progresses slowly, and in which neither cognitive decline nor dementia are
      prominent. These findings suggest a direct relation between SNCA gene dosage and
      disease progression.

PMID- 15451225
TI  - Causal relation between alpha-synuclein gene duplication and familial Parkinson's
      disease.
AB  - The alpha-synuclein gene (SNCA) has been implicated in autosomal dominant forms
      of Parkinson's disease. We screened 119 individuals from families with this rare
      form of the disease for SNCA duplications by semiquantitative multiplex PCR. Two
      patients had duplications, which were confirmed by analysis of intragenic and
      flanking microsatellite markers. The phenotype in both patients was
      indistinguishable from idiopathic Parkinson's disease and no atypical features
      were present, by contrast with reports of families with triplication of the same
      gene. These results indicate that SNCA is more frequently associated with
      familial Parkinson's disease than previously thought, and that there is a clear
      dosage effect according to the number of supernumerary copies of this gene.

PMID- 15451226
TI  - Klebsiella pneumoniae and pneumoperitoneum.

PMID- 15451227
TI  - Doxazosin in the sigmoid.

PMID- 15451228
TI  - Superficial fungal infections.
AB  - Superficial fungal infections arise from a pathogen that is restricted to the
      stratum corneum, with little or no tissue reaction. In this Seminar, three types
      of infection will be covered: tinea versicolor, piedra, and tinea nigra. Tinea
      versicolor is common worldwide and is caused by Malassezia spp, which are human
      saprophytes that sometimes switch from yeast to pathogenic mycelial form.
      Malassezia furfur, Malassezia globosa, and Malassezia sympodialis are most
      closely linked to tinea versicolor. White and black piedra are both common in
      tropical regions of the world; white piedra is also endemic in temperate
      climates. Black piedra is caused by Piedraia hortae; white piedra is due to
      pathogenic species of the Trichosporon genus. Tinea nigra is also common in
      tropical areas and has been confused with melanoma.

PMID- 15451229
TI  - Pleural mesothelioma: little evidence, still time to do trials.
AB  - CONTEXT: The incidence of malignant pleural mesothelioma is increasing throughout
      most of the world. This cancer is uniformly fatal, and characterised by
      progressive breathlessness and unremitting pain in the chest wall. From the onset
      of symptoms, survival is from a few weeks to a few years. Desperation by patients
      and doctors has driven a search for effective treatments. Clinical benefits are
      marginal and evidence of a good quality is lamentably lacking. STARTING POINT:
      David Sugarbaker is the world's leading proponent of extrapleural pneumonectomy
      (EPP), an operation in which all the pleura is removed with the lung,
      pericardium, and diaphragm. He has recently reported the complications of this
      radical surgery in a series of 496 operations (J Thorac Cardiovasc Surg 2004;
      128: 138-46). Although EPP as part of trimodality therapy (preoperative
      chemotherapy and postoperative radiation) is thought to be the best that can be
      offered and is regarded as the standard of care for selected patients given the
      morbidity associated with it, evidence for benefit is needed to justify its wider
      use. WHERE NEXT? With the increase in the number of cases there is increasing
      awareness of the disease, leading to earlier diagnosis, and an expectation that
      something must be done. Survival is short and the treatments on offer are
      onerous. The only responsible approach from a scientific, compassionate, or
      economic view (and why not combine all three?) is to find evidence of
      effectiveness to avoid futile and distressing treatment when possible.

PMID- 15451230
TI  - Preventing HIV/AIDS through poverty reduction: the only sustainable solution?

PMID- 15451231
TI  - In WHO's interest: the debate surrounding the 2003 election of the Director
      General of WHO.

PMID- 15451232
TI  - Coca-Cola and kangaroos.

PMID- 15451233
TI  - Fluoride release and recharge in giomer, compomer and resin composite.
AB  - OBJECTIVES: The aim of this study was to examine the fluoride recharging and
      releasing abilities of resin-based materials containing fluoridated glass filler
      to determine whether the extent of the glass-ionomer matrix of the material
      affects these properties. METHODS: Three materials having a different proportion
      of the hydrogel matrix surrounding the glass filler, namely: Reactmer paste,
      Dyract AP and Xeno CF, were used for this study. Five disk specimens of each
      material were placed into distilled/deionized water and the fluoride release
      measured during 38 days. For fluoride recharge the disks were exposed to 250 ppm
      F solution for 1 h and the pre- and post-recharge fluoride release were
      determined using an ion-selective electrode (total fluoride ions) and ion
      chromatography (free fluoride ions). RESULTS: The amounts of total and free
      fluoride release from each material at the initial period in descending order
      were Reactmer paste > Dyract AP > Xeno CF (p < 0.05 ANOVA and Scheffe's test).
      After fluoride recharge, Reactmer paste showed a greater amount of fluoride
      release than the other materials. Dyract AP and Xeno CF showed a similar total
      level of fluoride release after recharging. For Xeno CF the amount of total
      fluoride released after recharging was significantly greater than that of free
      fluoride, but there was no significant difference between total and free fluoride
      released after recharging for Dyract AP (p = 0.05 paired t-test). SIGNIFICANCE:
      These results suggested that the extent of the glass-ionomer matrix of the glass
      filler played an important role for fluoride-releasing and recharging abilities
      of the resin-based materials.

PMID- 15451234
TI  - Water movement in the hybrid layer after different dentin treatments.
AB  - The aim of this study was to examine the morphology of the hybrid layer (HL) of
      bonded water-stored specimens after different chemical pre-treatments of dentin.
      MATERIALS AND METHODS: Twenty-seven recently extracted human molars were
      selected. Fifty-four dentin disks in middle/deep dentin were obtained with a slow
      speed saw with a diamond-impregnated disk under water lubrication. Smear layers
      were created with 180 grit silicon carbide under running water for 1 min.
      Different pre-treatments of dentin were: Group (1) no treatment; Group (2) 35%
      H3PO4 etch for 15 s followed by 10% glutaraldehyde for 120 s; Group (3) 37% H3PO4
      etch for 15 s followed by 5% NaOCl for 120 s. Three dentin bonding agents (DBAs),
      Prime and Bond NT (P and B), AdmiraBond (AB), and Clearfil SE Bond (SEB) were
      applied in association with a resin composite following the manufacturers'
      directions. Each specimen was then longitudinally sectioned and polished with wet
      SiC papers (up to #4000 grit). Impressions of the polished dentin were
      immediately taken with a silicone impression material. Bonded specimens were then
      stored for 3 or 12 h in deionized water. Further impressions of stored specimens
      were taken after air-drying of specimens for 10 s. Positive replicas were
      obtained using a polyether impression material. All the replicas and the original
      specimens were inspected by SEM. RESULTS: A line of droplets (0.5-4 microm in
      diameter) was observed along the region of the adhesive-HL junction in all
      replicas of specimens stored in water, except in group 3, when P and B and AB
      were used. When SEB was used in each group the droplet were found in all groups
      except the zone of droplets was thinner. No differences in droplets dimensions
      were seen between 3 or 12 h water storage, or between the different dentin
      treatments. CONCLUSIONS: The replica procedure used in this study was able to
      detect water trapped in the adhesive-HL region that was released during the
      setting of the impression material. The droplets observed in this region support
      the hypothesis that there can be bidirectional water movement within the adhesive
      HL complex.

PMID- 15451235
TI  - The effect of a 3-methacryloxypropyltrimethoxysilane and vinyltriisopropoxysilane
      blend and tris(3-trimethoxysilylpropyl)isocyanurate on the shear bond strength of
      composite resin to titanium metal.
AB  - OBJECTIVES: The aim of this study was to evaluate the reactions of silanes prior
      to attaching the composite to titanium and evaluate these silanes as coupling
      agents. Veneered titanium may be used as a prosthetic material. METHODS: Two
      silane solutions, a mixture of both gamma-methacryloxypropyltrimethoxysilane and
      vinyltriisopropoxysilane, and tris(3-trimethoxysilylpropyl)isocyanurate were
      prepared as 2 wt% in two different (95% 2-propanol and 90% acetone) solutions. A
      control, 2 wt% gamma-methacryloxypropyltrimethoxysilane was prepared in both
      solutions. These six silane solutions were applied onto flat titanium surfaces.
      The samples (N = 250) were divided into two main groups: air-dried (room
      temperature) and heat cured for 1 h at 110 degrees C. Sinfony veneering composite
      was applied and light-cured on the titanium. The control group was non-silanized.
      The specimens were assigned to two subgroups: not thermocycled, and thermocycled
      (5000 cycles, 5-55 degrees C). Shear bond strength of the composite was tested at
      a crosshead speed of 1.0 mm min(-1). Fresh silane solution hydrolysis, and
      condensation reaction on titanium surface were monitored by FTIR spectrometry.
      RESULTS: Dry samples could be successfully tested, while thermocycling after 3700
      cycles had gradually de-bonded the composite from the silanized titanium
      substrate. For dry samples, statistical analysis (ANOVA) showed that solvent and
      silane significantly affected the shear bond strength. The silane mixture in 2
      propanol reacted at room temperature yielded 11.3 MPa (Standard deviation, SD,
      3.6 MPa) and on the other hand, tris(3-trimethoxysilylpropyl)isocyanurate in 2
      propanol yielded 10.7 MPa (SD 8.0 MPa) and gamma
      methacryloxypropyltrimethoxysilane 20.4 MPa (SD 12.2 MPa). Non-silanized samples
      yielded 4.8 MPa (SD 2.1 MPa). SIGNIFICANCE: In all solvents used, silanes reacted
      chemically with the titanium surface and covalent Si-O-Ti- and -Si-O-Si- bonds
      were evident.

PMID- 15451236
TI  - Investigation of initial pellicle formation on modified titanium dioxide (TiO2)
      surfaces by reflectometric interference spectroscopy (RIfS) in a model system.
AB  - OBJECTIVES: Plaque accumulation, leading to inflammatory processes and bone loss,
      is one of the main reasons for failure of dental implants. Pellicle formation
      plays a key role in bacterial adhesion and plaque accumulation. The influence of
      experimental bioactive implant surface coatings on the initial process of
      pellicle formation was investigated in a model system. METHODS: TiO2-films were
      modified by covalent binding of laminin and human epidermal growth factor (EGF)
      to promote adhesion of epithelial cells. Adsorption and dissociation behavior of
      bovine serum albumin (BSA) and salivary proteins on these surfaces were monitored
      by time-resolved reflectometric interference spectroscopy (RIfS). RESULTS: The
      thickness of the irreversibly adsorbed salivary protein layer was reduced from
      2.78 +/- 0.71 nm on unmodified TiO2 to 0.78 +/- 0.22 nm on laminin-coated
      surfaces and to 1.18 +/- 0.29 nm on EGF-coated surfaces. The percentage of
      initially adsorbed proteins remaining irreversibly bound was reduced from 51 +/-
      8% on titanium to 23 +/- 5% by laminin coating and to 44 +/- 11% on EGF-coated
      surfaces. The highest reduction of protein adsorption (layer thickness lower than
      0.05 nm) was achieved on DC-PEG-layers used as spacer for protein coupling.
      SIGNIFICANCE: Laminin and EGF were shown to be promising candidates for use as
      biological coatings on the transmucosal part of titanium dental implants where
      the objective is to enhance epithelial adhesion and inhibit adsorption of
      salivary proteins and bacteria.

PMID- 15451237
TI  - In vivo galvanic currents of intermittently contacting dental amalgam and other
      metallic restorations.
AB  - OBJECTIVE: It was the objective of this study to determine the magnitude of in
      vivo galvanic currents produced by simulating electrical contact between
      occluding metallic restorations, and to examine the influence of restoration age,
      difference in pre-contact corrosion potentials, and surface area. METHODS: A
      convenience sample of 106 human subjects was studied. A Ag/AgCl micro-reference
      electrode and a high impedance voltmeter were used to measure the pre-contact
      corrosion potentials. Galvanic couples (n = 194) were next formed by
      simultaneously contacting occluding restorations with gold-plated probe tips for
      15 s. The resulting current-time transients were measured with a zero-resistance
      ammeter and recorded with an electronic data acquisition program. The vast
      majority of couples measured contained at least one dental amalgam restoration.
      RESULTS: Galvanic current-time transients were typically characterized by an
      immediate and rapid rise to a peak current, followed by an exponential decay to a
      much lower value at 15 s. For couples with a restoration < or = 12 mo old, median
      peak current and median current at 15 s were 2.26 microA (range 0.24-13.06
      microA) and 0.57 microA (range 0.03-6.47 microA), respectively. For couples with
      a restoration >12 mo old, median peak current and median current at 15 s were
      1.40 microA (range 0.24-12.09 microA) and 0.37 microA (range 0.00-3.05 microA),
      respectively. Couples with fresh amalgams (< or = 6 mo) generally had elevated
      currents (range 2.56-102.54 microA). SIGNIFICANCE: A wide range of galvanic
      currents resulted from electrical contact of restorations in vivo. These currents
      were influenced by restoration age and total surface area of the galvanic couple.
      For amalgam-amalgam couples, the difference in the pre-contact corrosion
      potentials may be useful in predicting galvanic currents, when the difference is
      at least 24 mV.

PMID- 15451238
TI  - Relation in color of three regions of vital human incisors.
AB  - OBJECTIVES: For an adequate color reproduction, it is very valuable to quantify
      the color distribution in human teeth accurately. The aim of this study was to
      determine the color relation between three tooth segments (cervical, middle and
      incisal) in vital upper central incisors, using digital photography. METHODS:
      Digital recordings of 64 upper right central incisors were made using a
      standardized head-camera setup. The L*a*b* values of three regions were attained
      from the standardized digital images using software. RESULTS: There were
      statistically significant linear correlations for L* and b* between the three
      tooth segments (all r's > or = 0.60; p < 0.001). The correlation coefficient for
      a* was lower compared to L* and b* values. The L* and b* values of cervical and
      incisal tooth segment could be calculated from L* and b* values of middle tooth
      segment. SIGNIFICANCE: These results show the potency for color mapping of a
      whole tooth surface by extrapolation of color values of only one part of the
      surface.

PMID- 15451239
TI  - Effects of flowable resin on bond strength and gap formation in Class I
      restorations.
AB  - OBJECTIVES: This study measured resin/dentin bond strengths and evaluated gap
      formation at the pulpal floor of occlusal composite restorations using a flowable
      resin as a liner with either bulk or incremental placement of the restorative
      composite. METHODS: Class I occlusal preparations were made in 16 extracted
      molars, and were randomly divided into two groups for restoration using either
      One-Step adhesive (OS, BISCO) and Renew composite (RW, BISCO) or OptiBond SOLO
      adhesive (SOLO, Kerr) and Herculite XRV composite (XRV, Kerr). A flowable resin
      [AEliteFlo (AE, BISCO) or Revolution (RV, Kerr)] was applied as a liner in half
      of the specimens of each group. The lined and unlined groups were restored with
      composite cured in bulk, or cured in 1.5 mm increments. After 24 h in water, the
      teeth were sectioned into 0.7-mm thick slabs and were examined with an optical
      microscope (400 x) to determine the presence of internal resin-dentin gaps. The
      gap-free specimens were trimmed and were subjected to microtensile bond strength
      testing. Specimens that contained gaps had Knoop hardness of the restorative
      material measured. RESULTS: All incrementally filled restorations were well
      adapted to the pulpal floor but nearly all bulk-cured specimens had gaps between
      the flowable and the hybrid composites. The use of a flowable resin increased the
      bond strength of OS, but not SOLO. SIGNIFICANCE: The incremental technique
      prevented gap formation regardless of the use of a flowable resin. In contrast,
      the use of a flowable composite did not guarantee gap-free restorations or
      improved bond strength of resin to dentin in bulk-filled restorations.

PMID- 15451240
TI  - Pure titanium casting into zirconia-modified magnesia-based investment molds.
AB  - OBJECTIVE: Molten titanium is highly reactive with common mold materials at
      elevated temperatures. The aim of this investigation was to improve the accuracy
      of pure titanium casting by adding unreactive zirconia into magnesia-based
      investment material. METHODS: An automatic thermal expansion laser-recording
      machine (TEM-1000/Pantos, Nippon Co.) was used to measure thermal expansion of
      investment materials. An automatic argon-casting machine (Castmatic-S, Iwatani
      Co.) was used to cast pure titanium samples. A stereomicroscope was used (Nikon
      SM-2T, Japan) to measure marginal discrepancy on a metal die. A Vickers
      microhardness indenter (MXT-50, Matsuzawa Seiki Co.) determined the Vickers
      hardness (VH) of the titanium samples. Interfacial reactivity of the titanium was
      evaluated with an X-ray diffractometer (Rigaku D/max VIII, Tokyo, Japan). A
      dental X-ray machine was used to examine internal porosity of the castings. Data
      was analysed with paired t-test (p < 0.05), ANOVA/Tukey's HSD test (p < 0.001)
      and Spearman's correlation test (p < 0.05). RESULTS: Addition of 5.0-6.0 mass% of
      zirconia to a magnesia-based investment material significantly increased its
      thermal expansion value (p < 0.05). ANOVA indicated significant marginal
      discrepancy differences within the zirconia-added group (p < 0.001). There was a
      significant correlation between thermal expansion at 750 degrees C and marginal
      discrepancy (p < 0.05). The addition of zirconia decreased interfacial reactivity
      and the VH of titanium. SIGNIFICANCE: Under appropriately adjusted conditions,
      the addition of zirconia to magnesia-based mold materials may be used to produce
      high quality pure titanium castings.

PMID- 15451241
TI  - Effect of bleaching on restorative materials and restorations--a systematic
      review.
AB  - OBJECTIVE: Internal and external bleaching procedures utilizing 3-35% hydrogen
      peroxide solutions or hydrogen peroxide releasing agents, such as carbamide
      peroxide or sodium perborate, can be used for whitening of teeth. The purpose of
      the review article was to summarize and discuss the available information
      concerning the effects of peroxide releasing bleaching agents on dental
      restorative materials and restorations. SOURCES: Information from all original
      scientific full papers or reviews listed in PubMed or ISI Web of Science (search
      term: bleaching AND (composite OR amalgam OR glass ionomer OR compomer OR resin
      OR alloy) were included in the review. DATA: Existing literature reveals that
      bleaching therapies may have a negative effect on physical properties, marginal
      integrity, enamel and dentin bond strength, and color of restorative materials as
      investigated in numerous in vitro studies. However, there are no reports in
      literature indicating that bleaching may exert a negative impact on existing
      restorations requiring renewal of the restorations under clinical conditions.
      CONCLUSION: Bleaching may exert a negative influence on restorations and
      restorative materials. Advice is provided based on the current literature to
      minimize the impact of bleaching therapies on restorative materials and
      restorations.

PMID- 15451242
TI  - Stress distributions in adhesively cemented ceramic and resin-composite Class II
      inlay restorations: a 3D-FEA study.
AB  - OBJECTIVES: The purpose of this study was to investigate the effect of
      differences in the resin-cement elastic modulus on stress-transmission to ceramic
      or resin-based composite inlay-restored Class II MOD cavities during vertical
      occlusal loading. METHODS: Three finite-element (FE) models of Class II MOD
      cavity restorations in an upper premolar were produced. Model A represented a
      glass-ceramic inlay in combination with an adhesive and a high Young's modulus
      resin-cement. Model B represented the same glass-ceramic inlay in combination
      with the same adhesive and a low Young's modulus resin-cement. Model C
      represented a heat-cured resin-composite inlay in combination with the same
      adhesive and the same low Young's modulus resin cement. Occlusal vertical loading
      of 400 N was simulated on the FE models of the restored teeth. Ansys FE software
      was used to compute the local von Mises stresses for each of the models and to
      compare the observed maximum intensities and distributions. Experimental
      validation of the FE models was conducted. RESULTS: Complex biomechanical
      behavior of the restored teeth became apparent, arising from the effects of the
      axial and lateral components of the constant occlusal vertical loading. In the
      ceramic-inlay models, the greatest von Mises stress was observed on the lateral
      walls, vestibular and lingual, of the cavity. Indirect resin-composite inlays
      performed better in terms of stress dissipation. Glass-ceramic inlays transferred
      stresses to the dental walls and, depending on its rigidity, to the resin-cement
      and the adhesive layers. For high cement layer modulus values, the ceramic
      restorations were not able to redistribute the stresses properly into the cavity.
      However, stress-redistribution did occur with the resin-composite inlays.
      SIGNIFICANCE: Application of low modulus luting and restorative materials do
      partially absorb deformations under loading and limit the stress intensity,
      transmitted to the remaining tooth structures.

PMID- 15451243
TI  - Immediate performance of self-etching versus system adhesives with multiple light
      activated restoratives.
AB  - OBJECTIVES: The purpose of this study was to evaluate the performance of both
      single and double applications of (Adper Prompt L-Pop) self-etching dental
      adhesive, when used with three classes of light-activated restorative materials,
      in comparison to the performance of each restorative system adhesive. Evaluation
      parameters to be considered for the adhesive systems were (a) immediate marginal
      adaptation (or gap formation) in tooth cavities, (b) free setting shrinkage
      strain determined by the immediate marginal gap-width in a non-bonding Teflon
      cavity, and (c) their immediate shear bond-strengths to enamel and to dentin.
      METHODS: The maximum marginal gap-width and the opposing-width (if any) in the
      tooth cavities and in the Teflon cavities were measured immediately (3 min) after
      light-activation. The shear bond-strengths to enamel and to dentin were also
      measured at 3 min. RESULTS: For light-activated restorative materials during
      early setting (<3 min), application of Adper Prompt L-Pop exhibited generally
      superior marginal adaptation to most system adhesives. But there was no
      additional benefit from double application. The marginal-gaps in tooth cavities
      and the marginal-gaps in Teflon cavities were highly correlated (r = 0.86-0.89, p
      < 0.02-0.01). For enamel and dentin shear bond-strengths, there were no
      significant differences between single and double applications, for all materials
      tested except Toughwell and Z 250 with enamel. SIGNIFICANCE: Single application
      of a self-etch adhesive was a feasible and beneficial alternative to system
      adhesives for several classes of restorative. Marginal gap-widths in tooth
      cavities correlated more strongly with free shrinkage-strain magnitudes than with
      bond-strengths to tooth structure.

PMID- 15451244
TI  - Resistance to sliding of orthodontic brackets with bumps in the slot floors and
      walls: effects of second-order angulation.
AB  - OBJECTIVE: Two stainless steel (SS) bracket designs with two bumps across the
      slot floors and rounded slot walls and one polycrystalline alumina (PCA) bracket
      design with one bump along the slot floor were compared to conventional SS and
      PCA brackets. METHODS: For each design, the resistances to sliding of four
      archwire-bracket couples, two in the dry state and two in the wet (saliva) state,
      were measured at 32 second-order angles between -12 and +12 degrees. RESULTS:
      When clearances existed, the kinetic coefficients of friction of the SS brackets
      ranged from 0.13 to 0.15 in the dry state and from 0.17 to 0.18 in the wet state.
      For the PCA brackets, the kinetic coefficients of friction were 0.18 for both
      designs in the dry state and were 0.18 for the brackets with bumps and 0.24 for
      the brackets without bumps in the wet state. SIGNIFICANCE: Overall, the bumps and
      rounded slot walls did not reduce classical friction. When the brackets with
      rounded slots were modeled, the critical contact angles for binding were larger
      than the values based on the apparent dimensions, but were less than those based
      on the true dimensions. When clearances did not exist, the rates of binding were
      greater for the SS brackets with bumps and rounded walls than for the
      conventional brackets. The rates of binding increased because the rounded walls
      forced the archwires into complex shapes. Both PCA bracket designs had similar
      rates of binding; but unlike the conventional design, the brackets with the bumps
      did not permanently deform the archwires at large angles.

PMID- 15451245
TI  - Mathematical analysis of tooth and restoration contour using image analysis.
AB  - OBJECTIVES: The aim of this study was to develop a methodology for comparison of
      the contour of artificial crowns in the mid bucco-lingual plane with their
      equivalent natural teeth on the opposing side of the same arch (antimeres) using
      a novel application of image analysis software. The objective was to determine
      whether artificial crowns were overcontoured. METHODS: Specimens consisted of
      thin sections of silicone putty impressions of the buccal and lingual surfaces of
      55 full crown restorations and their natural antimeric teeth. A thin slice of the
      putty was obtained in the mid-tooth bucco-lingual plane and a digital image was
      captured and this was analysed to produce a data set (x, y) representing the
      curvature of the tooth surface. Further analysis was performed in order to
      describe the profile in optimum mathematical terms. RESULTS: The curves were best
      represented by three equations: y = a + bx(0.5), ln(y) = a + bx2, and y2 = a +
      bx. In all equations parameter (b), which expresses the contour curvature, was
      used as a deciding factor in comparing the degree of contour of the crown
      restorations with their natural antimeres. Most artificial crowns were found to
      be either similarly or undercontoured when compared with their natural antimeres.
      When overcontouring was present in the artificial crowns this tended to occur on
      the lingual aspects of anterior and posterior crowns. SIGNIFICANCE: Simplifying
      tooth contour into a mathematical model can be useful in determining whether
      restorations are overcontoured. Clinically, particular attention should be
      directed towards the lingual aspects of restorations which were more likely to be
      overcontoured.

PMID- 15451246
TI  - Immunization in heifers with dual vaccines containing Tritrichomonas foetus and
      Campylobacter fetus antigens using systemic and mucosal routes.
AB  - Vaccines against both bovine venereal campylobacteriosis and trichomonosis were
      tested. Heifers were assigned to three groups. Groups 1 (n = 21 heifers) and
      group 2 (n = 20) received a commercial or experimental vaccine, respectively,
      containing both Campylobacter fetus and Tritrichomonas foetus antigens. Group 3
      (n = 21) received adjuvant alone. Preparations were injected SQ in groups 1 and 3
      at days -60 and -30 (day 0 was considered the first day of a 90-day breeding
      period), and in group 2 SQ at days -30 and +11 and into the vaginal submucosa at
      day -9. Heifers were exposed to two pathogen-infected bulls for 90 days (from day
      0 to day +90); furthermore, half of the heifers in each group were challenged at
      day +39 by an intravaginal instillation of C. fetus venerealis and T. foetus.
      Pregnancy diagnosis, vaginal culture, and determination of systemic IgG for both
      organisms were performed. Compared to controls, vaccinated heifers resisted or
      quickly cleared both pathogens, had a higher pregnancy rate and a higher systemic
      immune response during and after the breeding period. Overall, the experimental
      vaccine was superior to the commercial vaccine (groups 2 and 1, respectively). In
      conclusion, an experimental vaccine containing both C. fetus and T. foetus
      antigens, given both SQ and intravaginal immediately before breeding and early in
      the breeding season, yielded superior protection for heifers exposed to bulls
      harboring C. fetus and T. foetus.

PMID- 15451247
TI  - Isolation of E. coli from foam and effects of fluoroquinolones on E. coli and
      foam production in male Japanese quail.
AB  - Sexually active male Japanese quail (Coturnix coutrnix Japonica) produce a foamy
      substance from their cloacal gland. It was postulated that bacteria played an
      important role in production of foam. The primary objective of this study was to
      isolate and identify bacteria present in the cloacal foam. The secondary
      objective was to evaluate the effect of fluoroquinolone treatment on bacterial
      counts and foam production. Healthy adult Japanese quail were maintained in
      individual cages under uniform husbandry conditions and allocated arbitrarily
      into three groups (each group consisted of 12 male and 12 female birds). Foam was
      collected from the cloacal gland of male birds of each group separately into
      sterile petri dishes and was cultured to isolate and identify bacteria and to
      determine their sensitivity to various antibiotics. Escherichia coli bacteria,
      sensitive to various antibacterials (including the fluoroquinolones ciprofloxacin
      and pefloxacin), were isolated. In the second part of the study, male quails of
      Group I (control) received I mL vehicle (normal saline 0.9% (w/v) NaCl) daily
      (via the intraperitoneal route) for 12 days. Male birds from groups II and III
      were treated intraperitoneally with ciprofloxacin or pefloxacin at the rate of 10
      mg and 12 mg per/kg body weight respectively, for 12 days. In antibiotic-treated
      birds, there was a gradual reduction in foam production during treatment. At the
      end of treatment, the cloacal gland area was smaller (P < 0.05) in pefloxacin
      treated birds compared to the other groups. Furthermore, a trend towards
      decreasing body weight and fertilizing ability was noted in the same group. A
      drastic reduction in bacterial counts of foam was recorded only in
      fluoroquinolone-treated groups during treatment period. After cessation of
      treatment, all end points were increasing back to pre-treatment levels. In
      conclusion, E. coli were present in the foam of the cloacal gland of Japanese
      quail and may have a role in foam production.

PMID- 15451248
TI  - Changes in plasma gonadotropin concentrations and urethral closure pressure in
      the bitch during the 12 months following ovariectomy.
AB  - Urinary incontinence due to acquired urethral sphincter incompetence is a common
      side effect of spaying, for which the underlying cause remains unknown. Spaying
      not only results in a significant reduction in the urethral closure pressure
      within 1 year but also in an increase in the plasma gonadotropin concentrations.
      To investigate the possible link between the post-ovariectomy changes in plasma
      gonadotropins and in urethral closure pressure, gonadotropin and urodynamic
      measurements were performed in 10 Beagle bitches before and for a period of 1
      year after spaying. Plasma gonadotropin concentrations rose quickly after
      ovariectomy and peak levels were seen within 3-5 weeks, followed by a sharp drop
      until week 10. A steady increase was observed subsequently until week 42, when a
      plateau was reached. One year after spaying, the mean FSH concentration was 75.3
      +/- 32.1 ng/ml, a 17-fold increase, and the LH was 8.3 +/- 3.8 ng/ml, an
      eightfold increase over the pre-spaying values. Ten months after spaying, the
      mean urethral closure pressure (9.7 cm H2O) was significantly reduced when
      compared to the mean pre-operative value of 15.4 cm H2O. However, there was no
      clear relationship between the gonadotropin concentrations and the urethral
      closure pressure. From these results it seems unlikely that chronically elevated
      gonadotropins are the underlying cause for reduced urethral closure pressure
      after spaying resulting in urinary incontinence.

PMID- 15451249
TI  - Effect of protein supplementation in potassium simplex optimization medium on
      preimplantation development of bovine non-transgenic and transgenic cloned
      embryos.
AB  - The present study evaluated the effect of protein supplementation in potassium
      simplex optimization medium (KSOM) on bovine preimplantation embryo development.
      The in vitro fertilized (IVF) (Experiment 1), non-transgenic (Experiment 2) and
      transgenic cloned embryos (Experiment 3) were cultured for 192 h in KSOM
      supplemented with 0.8% BSA (KSOM-BSA), 10% FBS (KSOM-FBS) or 0.01% PVA (KSOM
      PVA). Transfected cumulus cells with an expression plasmid for human alpha1
      antitrypsin gene and a green fluorescent protein (GFP) marker were used to
      produce transgenic cloned embryos. Modified synthetic oviductal fluid (mSOF)
      supplemented with 0.8% BSA (mSOF-BSA) was used as a control medium. In Experiment
      1, cleavage rate was significantly (P < 0.05) lower (69.1%) in IVF embryos
      cultured in KSOM-FBS than in KSOM-BSA (80.3%). The rate of hatching/hatched
      blastocyst formation was significantly (P < 0.05) lower in embryos cultured in
      KSOM-PVA than in KSOM-FBS (2.2% versus 10.8%). Blastocysts cultured in KSOM-FBS
      contained significantly (P < 0.06) higher numbers of inner cell mass cells (50.4
      +/- 20.2) than those cultured in mSOF-BSA (36.9 +/- 19.2). In Experiment 2, the
      rate of blastocyst formation was significantly (P < 0.05) lower (20.5%) in
      embryos cultured in KSOM-PVA than in other culture media (33.3-38.5%). The rate
      of hatching/hatched blastocysts was significantly (P < 0.05) lower in KSOM-PVA
      (13.9%) and KSOM-FBS (17.1%) than in KSOM-BSA (30.8%) and mSOF-BSA (33.9%). The
      numbers of total and trophectoderm cells (104.6 +/- 32.2 and 71.7 +/- 25.5,
      respectively) were significantly (P < 0.05) lower in blastocysts cultured in KSOM
      PVA than in KSOM-BSA (125.7 +/- 39.7 and 91.7 +/- 36.2, respectively). In
      Experiment 3, no significant differences in embryo development, GFP expression
      and blastocyst cell numbers were observed among the culture groups. In
      conclusion, the present study demonstrated that KSOM and mSOF supplemented with
      BSA were equally effective in supporting development of bovine non-transgenic and
      transgenic cloned embryos. Moreover, different developmental competence in
      response to protein supplementation of KSOM was observed between bovine non
      transgenic and transgenic cloned embryos.

PMID- 15451250
TI  - Effect of time of ovulation on fertilization after intrabursal transfer of
      spermatozoa (ITS): improvement of a new method for artificial insemination in
      mice.
AB  - The timing of AI in relation to ovulation was examined to improve intrabursal
      transfer of spermatozoa (ITS) in mice, a new method of AI that involves transfer
      of spermatozoa into a space near the infundibulum. Two microliters of fresh
      epididymal B6C3F1 spermatozoa (containing 2 x 10(5) spermatozoa) were inseminated
      1, 7, 12, or 17 h after hCG administration. At 1.7 days after ITS, normal
      cleaving embryos were recovered at rates ranging from 6 to 50% (21.5 +/- 15.8%;
      mean +/- S.D.), 40-100% (75.2 +/- 20.2%), 33-100% (60.1 +/- 19.3%), and 6-47%
      (22.7 +/- 13.3%), respectively. The rate obtained by ITS 7h after hCG
      administration was comparable (P > 0.05) to that (90.5 +/- 6.3%) for embryos
      obtained after natural mating (control), but rates at all other times were
      significantly less than control. To examine whether in vivo fertilization rate
      differs when spermatozoa from various mouse strains are used, B6C3F1 females were
      inseminated with spermatozoa from ICR, C57BL/6N and C3H/HeN mice 7 h after hCG
      administration. There were strain differences (P < 0.01 for ICR and B6C3F1 versus
      C57BL/6N and C3H/HeN) for in vivo fertilization rates (83.9 +/- 10.3%, 75.2 +/-
      20.2%, 33.6 +/- 24.5% and 25.6 +/- 16.1% for ICR, B6C3F1, C57BL/6N and C3H/HeN,
      respectively). Similar rates (72.9 +/- 7.3% and 27.5 +/- 46.2% for ICR and
      C57BL/6N, respectively) were also obtained when oocytes were inseminated with
      spermatozoa of the same strain. In addition, females (B6C3F1) inseminated by ITS
      of fresh B6C3F1 spermatozoa 7 h after hCG administration yielded normal mid
      gestational fetuses with an average litter size of 7.0 +/- 4.9, which seemed much
      higher than the previously reported litter size of 3.2. In conclusion, the timing
      of AI was considered a key factor affecting in vivo fertilization efficiency.

PMID- 15451251
TI  - Correlation between fetal age and ultrasonographic measurements during the second
      half of pregnancy in domestic cats (Felis catus).
AB  - We ultrasonographically evaluated the prenatal development in cats, from Day 30
      to the end of pregnancy, subjecting a group of pregnant cats (n = 8) to daily
      ultrasonographic examinations. The ultrasonographic images allowed us to measure
      the diameter of the fetal abdomen, the biparietal diameter of the fetal skull and
      the diameter of the fetal stomach. A correlation between these measurements and
      gestational age was found with a linear, parabolic and exponential regression
      analysis. From Days 38 to 43 after breeding we also performed fetal gender
      determination by evaluating the external genitalia. All queens successfully
      carried their pregnancies to term. This study compiled useful new data in order
      to clinically monitor the normal course of pregnancy in cats and to determine
      gestational age.

PMID- 15451252
TI  - Effects of an experimental Trypanosoma congolense infection on the reproductive
      performance of West African Dwarf goats.
AB  - Thirty-six West African Dwarf (WAD) goats were used to assess the effects of an
      experimental Trypanosoma congolense infection on their reproductive system.
      Estrous cycles were synchronised and when confirmed pregnant (n = 31), the does
      were randomly allocated into control and trypanosome-infected groups. After
      infection, the animals were carefully observed till parturition. Trypanosome
      infection caused an increase of rectal temperature, a significant drop in PCV
      (infected: 23.3 +/- 0.3%; control: 28.5 +/- 0.4%; P < 0.0001) and abortions in
      27.8% of the infected does. Kids born from infected does had a lower birth weight
      than kids born from control goats (0.9 +/- 0.1 kg versus 1.6 +/- 0.1 kg; P <
      0.0001). Eight out of 13 kids (61.5%) that were born alive from infected does
      died during their first week of life. Plasma pregnancy-associated glycoprotein
      (PAG) and progesterone concentrations were lower in the infected animals than in
      the controls. In general, PAG concentration in does which aborted dropped before
      abortion. Our results revealed that artificial T. congolense infection affected
      reproductive performance of WAD goats with abortions, premature births and
      perinatal losses being observed. Neither transplacental transmission of T.
      congolense nor histopathological lesions of the placenta could be demonstrated.

PMID- 15451253
TI  - Sexing using single blastomere derived from IVF bovine embryos by fluorescence in
      situ hybridization (FISH).
AB  - Fluorescence in situ hybridization (FISH) is a sensitive technique for molecular
      diagnosis of chromosomes on single cells and can be applied to sex determination
      of embryos. The objective has been to develop an accurate and reliable bovine Y
      chromosome-specific DNA probe in order to sex biopsed blastomeres derived from
      IVF bovine embryos by FISH. Bovine Y chromosome-specific PCR product derived from
      BtY2 sequences was labeled with biotin-16-dUTP (BtY2-L1 probe), and FISH was
      performed on karyoplasts of biopsed blastomeres and matched demi-embryos. Our
      FISH signal was clearly detected in nuclei of blastomeres of male embryos. FISH
      analysis of bovine embryos gave high reliability (96%) between biopsied
      blastomeres and matched demi-embryos. These results indicated that the BtY2-L1
      bovine Y chromosome-specific FISH probe was an effective probe for bovine embryo
      sexing, and the FISH technique of probe detection could improve the efficiency
      and reliability.

PMID- 15451254
TI  - Genetic parameters of multiple ovulation traits in Nellore females.
AB  - Variability in superovulatory response is a limiting factor for animal breeding
      programs using Multiple Ovulation and Embryo Transfer (MOET) nucleus schemes. To
      evaluate genetic factors affecting superovulory response, 1036 multiple ovulation
      records from 475 Brazilian Nellore embryo donors (daughters of 139 sires), 2.2
      20.5-year olds, were analyzed. Traits used to evaluate superovulatory response
      included the number of palpable corpora lutea (CL), the total number of recovered
      structures (RS), and the number of viable embryos (VE). Two data sets were used:
      data from the first flush only or data from the first three flushes. Genetic
      parameter estimations were carried out using Restricted Maximum Likelihood (REML)
      methodology, with single- and multiple-trait animal models. According to the data
      set used, heritability estimates ranged from 0.47 to 0.57 for CL, from 0.20 to
      0.65 for VE, and from 0 to 0.34 for RS, and were higher for the data set that
      used only the first flushing only. For the first flush, genetic correlations were
      0.43 between CL and SF, 0.01 between CL and VE, and 0.73 between SF and VE.
      Repeatability estimates ranged from 0.47 to 0.51. In conclusion, the use of data
      from the first flush only might result in better estimates of genetic parameters
      for MOET traits in Nellore females. Furthermore, moderate to high values for
      repeatability suggested that selection for a high response to superovulation
      could be made after the first flush.

PMID- 15451255
TI  - Production of a healthy calf by somatic cell nuclear transfer without
      micromanipulators and carbon dioxide incubators using the Handmade Cloning (HMC)
      and the Submarine Incubation System (SIS).
AB  - The aim of this work was to investigate the minimum technical requirements for
      production of live offspring with somatic cell nuclear transfer. The experiment
      was performed in a field type laboratory without micromanipulators and carbon
      dioxide incubators. All long-term incubations were performed in the Submarine
      Incubation System (SIS) using various gas mixtures. The somatic cell culture was
      established from ear biopsy of a 9-year-old Holstein cow. Nuclear transfer was
      performed using the Handmade Cloning (HMC) technique. Zona-free oocytes were
      randomly bisected by hand with a disposable blade and a stereomicroscope.
      Cytoplast were selected using Hoechst staining and a fluorescent microscope.
      After a two-step fusion embryos were activated with calcium ionophore and
      dimethylaminopurine. Embryos were cultured in microwells (WOWs) in SOFaaci medium
      supplemented with 5% cattle serum. In two consecutive experiments, six
      blastocysts were produced from 52 reconstructed embryos. On Day 7, five
      blastocysts were transferred into synchronized recipients. All three recipients
      became pregnant but two pregnancies aborted at 6 and 7 months, respectively. A
      heifer calf weighing 27 kg was delivered at term by Caesarean section from the
      third pregnancy. The healthy 6-month-old heifer, the first cloned animal of
      Africa, is living evidence that nuclear transfer technology may be successfully
      used under basic laboratory conditions.

PMID- 15451256
TI  - Effects of amino acids on maturation, fertilization and embryo development of pig
      follicular oocytes in two IVM media.
AB  - This study was conducted to develop a serum-free, defined medium for IVM of pig
      oocytes. Modified North Carolina State University (mNCSU)-23 media with or
      without supplementation with both epidermal growth factor (EGF) and gonadotrophin
      were used as base media. In separate experiments, each base medium was
      supplemented with porcine follicular fluid (pFF), polyvinyl alcohol (PVA), PVA
      and essential amino acids (EAA), PVA and nonessential amino acids (NEAA) or PVA
      with both EAA and NEAA. Averaged across these five treatments, the percentage of
      blastocyst formation was higher (P < 0.05) in the base medium supplemented with
      EGF and gonadotrophins. In both base media, the addition of NEAA yielded similar
      percentages of maturation (81-82% versus 75-80%), sperm penetration (89-93%
      versus 80-86%) and blastocyst formation (4-18% versus 4-13%) as media
      supplemented with pFF. Although similar benefits were found after the addition of
      EAA, their addition was associated with lower (P < 0.05) maturation (66%) and
      sperm penetration (58%) than when pFF was added to the base medium without EGF
      and gonadotrophins. However, decreased maturation after EAA addition was not
      detected in the base medium containing EGF and gonadotrophins. Within the same
      base medium, monospermy, male pronucleus formation, cleavage and blastocyst
      formation were not affected by the treatments; and combined addition of EAA and
      NEAA did not further improve oocyte development. In conclusion, a maturation
      system using a defined mNCSU-23 medium supplemented with EGF, gonadotrophins and
      EAA or NEAA was developed which yielded a similar number of blastocysts compared
      with a pFF-containing medium.

PMID- 15451257
TI  - Follicle size-dependent effects of sow follicular fluid on in vitro cumulus
      expansion, nuclear maturation and blastocyst formation of sow cumulus oocytes
      complexes.
AB  - Follicular fluid from 2 to 4 and 5 to 8 mm diameter non-atretic follicles (SFF
      and LFF, respectively) of sows was added during IVM of cumulus oocytes complexes
      (COCs) to study its effects on cumulus expansion, nuclear maturation, and
      subsequent fertilization and embryo development in presence or absence of
      recombinant human FSH. COCs aspirated from 2 to 5 mm follicles of sow ovaries,
      were cultured for the first 22 h in TCM-199 and 100 microM cysteamine, with or
      without 10% pFF and/or 0.05 IU/ml recombinant hFSH. For the next 22 h, the COCs
      were cultured in the same medium, but without pFF and FSH. After culture, cumulus
      cells were removed and the oocytes were either fixed and stained to evaluate
      nuclear stages or co-incubated with fresh sperm. Twenty-four hours after
      fertilization, presumptive zygotes were fixed to examine fertilization or
      cultured for 6 days to allow blastocyst formation. Subsequently, embryos were
      evaluated and the blastocysts were fixed and stained to determine cell numbers.
      When LFF was added to maturation medium, cumulus expansion and percentage of
      nuclear maturation (277 +/- 61 microm and 72%, respectively) of COCs were
      significantly higher (P < 0.05) than those in SFF (238 +/- 33 microm and 55%,
      respectively). However, in the presence of FSH both FF stimulated cumulus
      expansion and nuclear maturation to a similar degree. No differences were
      observed with regards to sperm penetration, male pronucleus formation, and to
      polyspermia between fertilized oocytes matured either in SFF or LFF. Fertilized
      oocytes matured in the presence of LFF without or with FSH showed a higher
      cleavage (45 +/- 7% and 51 +/- 7%, respectively) and blastocyst (14 +/- 4% and 22
      +/- 6%, respectively) formation rate compared to SFF (cleavage, 35 +/- 8% and 41
      +/- 4%, blastocyst: 8 +/- 3 and 13 +/-3, respectively; P < 0.05). The mean number
      of cells per blastocyst did not differ significantly between treatments. These
      findings indicate that factor(s) within follicles at later stages of development
      play an important role during oocyte maturation and thereby enhance developmental
      competence to occur.

PMID- 15451258
TI  - Influence of glucose and fructose in the extender during long-term storage of
      chilled canine semen.
AB  - The use of chilled, extended semen in dog breeding is becoming increasingly
      popular as preparation and transportation is less expensive and regulations are
      often less complicated than for frozen semen. Sugar is one of the main
      constituents in semen extenders, and glucose and fructose are metabolized in
      separate pathways by freshly ejaculated dog sperm. In this study, glucose,
      fructose or an equal mixture of both were used in an egg-yolk-tris (EYT) extender
      at two different concentrations (10 and 70 mM). EYT extender without sugar
      supplementation, providing only the glucose (3-4 mM) originating from the egg
      yolk, served as a control. The longevity of the chilled semen at 5 degrees C was
      23 days: the quality of physical and functional characteristics decreasing with
      time. Glucose and fructose had a strong influence on motility and movement
      patterns of chilled canine semen. The beneficial effect of 70 mM sugar
      concentrations compared to 10 mM and the control was pronounced, and maintained
      sperm motility > or = 70% for 8 days of storage, compared to for 4 days in the
      control extender. Fructose maintained higher sperm motility than did glucose and
      the mixture. VAP values were higher in sugar-supplemented extenders (P < 0.05).
      Neither type nor concentration of the two sugars influenced sperm plasma
      membrane, acrosome integrity or the acrosome reaction following ionophore
      challenge (ARIC). Sugar consumption by dog sperm varied between the different
      periods of storage and with sugar concentrations provided in the extenders.
      Glucose consumption by dog sperm was greater than fructose consumption when both
      sugars were present in equal amounts, indicating that dog sperm used glucose in
      preference to fructose. In conclusion, the major influence of the two sugars on
      chilled semen was to support motility. EYT extender supplemented with fructose at
      a concentration of 70 mM was found to be the best of the tested extenders for
      long-term preservation of chilled canine semen.

PMID- 15451259
TI  - Estrus synchronization in beef heifers with progestin-based protocols. I.
      Differences in response based on pubertal status at the initiation of treatment.
AB  - Two progestin-based protocols for estrus synchronization in replacement beef
      heifers were compared on the basis of estrous response, interval to and synchrony
      of estrus, and pregnancy rate. The objective was to determine, whether addition
      of GnRH to a melengestrol acetate (MGA)-prostaglandin F2alpha (PGF2alpha) estrus
      synchronization protocol would improve synchrony of estrus without compromising
      fertility in yearling beef heifers. Heifers at two locations (Location 1, n = 60
      and Location 2, n = 64) were assigned randomly to one of two treatments by breed
      and pubertal status. Heifers were defined as, pubertal when concentrations of
      progesterone in serum were elevated (> or = 1 ng/mL) in either one of two samples
      obtained 10 and 1 day prior to treatment initiation. Prior to MGA administration,
      18/60 (30%) and 36/64 (56%) of the heifers at Locations 1 and 2, respectively,
      were pubertal. Heifers in both treatments were fed MGA (0.5 mg/head/day in 1.8
      kg/head/day supplement) for 14 days followed by 25 mg of PGF2alpha i.m. (MGA
      PGF2alpha) 19 days after MGA withdrawal (Day 33 of treatment). One-half of the
      heifers at each location received 100 microg of GnRH i.m. 12 days after MGA
      withdrawal (Day 26 of treatment; MGA Select). The control group received only MGA
      PGF2alpha. Heifers were observed for signs of behavioral estrus continuously
      during daylight hours for 7 days beginning on the day PGF2alpha was administered.
      Heifers were inseminated 12 h after observed estrus. There was a treatment by
      location by pubertal status interaction (P < 0.05) for interval to estrus.
      Compared to the respective control treatment at each location, prepubertal
      heifers assigned to the MGA Select protocol at Location 1 had longer intervals to
      estrus, whereas at Location 2, prepubertal heifers assigned to the MGA-PGF2alpha
      protocol had longer intervals to estrus. The higher number of pubertal heifers at
      Location 2 was associated with a reduced variance in the interval to estrus among
      MGA Select treated heifers. Total estrous response and synchronized conception
      rates were similar between treatments at both locations. These data suggest that
      addition of GnRH to the MGA-PGF2alpha protocol may improve synchrony of estrus,
      however, the degree of synchrony may be influenced by pubertal status of heifers
      at the time treatments are imposed. Further studies are needed to define
      production systems in which the MGA Select protocol is warranted for use in beef
      heifers.

PMID- 15451260
TI  - Progesterone supplementation during the early fetal period reduces pregnancy loss
      in high-yielding dairy cattle.
AB  - It was hypothesized that sub-optimal progesterone concentrations during the late
      embryo and early fetal period may act to compromise conceptus development in
      dairy cattle. The aim of the present study was to test this hypothesis by
      supplementing pregnant cows with exogenous progesterone following pregnancy
      diagnosis. The study population consisted of 1098 pregnant lactating cows.
      Pregnancy was diagnosed by transrectal ultrasonography between 36 and 42 days
      after insemination. Animals found to be pregnant were randomly assigned to the
      Control (untreated cows, n = 549) or Treatment (n = 549) groups. Cows in group
      Treatment were fitted at pregnancy diagnosis with a progesterone releasing
      intravaginal device (PRID) containing 1.55 g of progesterone, for 28 days. Cows
      were then subjected to a further diagnosis by palpation per rectum on Day 90 of
      gestation. Pregnancy loss was registered in 95 (8.7%) cows on Day 90 of
      pregnancy: 66 (12%) in group Control and 29 (5.3%) in group Treatment. Logistic
      regression analysis indicated that there were no significant effects of herd,
      bull, milk production, service number, days in milk at pregnancy and lactation
      number. Based on the odds ratio, treated cows were 2.4 (1/0.41) times less likely
      to miscarry, whereas the risk of pregnancy loss was 1.6 times higher in cows that
      became pregnant during the warm period in comparison to the cool period. These
      results support the hypothesis that sub-optimal progesterone concentrations in
      high producer dairy cows may compromise conceptus development. Under these
      conditions, intra-vaginal progesterone supplementation has the potential to
      reduce the incidence of pregnancy loss during the early fetal period.

PMID- 15451261
TI  - Cloning of Taiwan water buffalo male-specific DNA sequence for sexing.
AB  - Random amplified polymorphic DNA (RAPD) fingerprinting was carried out to
      investigate the sex-specific DNA sequence for sexing in Taiwan water buffalos.
      One hundred and forty random primers were used for RAPD-PCR (polymerase chain
      reaction). One of these primers, OPC-16, produced a 321 bp fragment found only in
      tested males. This male-specific fragment was isolated and constructed into
      plasmids for nucleotide sequencing, a novel male-specific sequence was obtained.
      Two primers (BuSexOPC16-F and -R) were designed according to the cloned male
      specific sequence to amplify the male-specific fragment using PCR for sexing. Sex
      specific bands in the gel were represented in the males but none were found in
      the females when the Taiwan water buffalo genomic DNA samples were amplified with
      these two primers using PCR. The same results were also obtained from Taiwan
      yellow, Holstein, Angus, and Hereford cattle samples. This showed that the sex of
      these five breeds could be easily and effectively determined using the PCR
      technique.

PMID- 15451262
TI  - Birth of piglets by in vitro fertilization of zona-free porcine oocytes.
AB  - The present experiments were conducted to optimize in vitro fertilization
      conditions for zona pellucida-free (ZP-free) oocytes and their subsequent
      development. The results demonstrated that: (1) maximal fertilization efficiency
      was achieved at 200 spermatozoa per ZP-free oocyte. At this sperm dose, there
      were no significant differences in penetration rates and polyspermy rates from
      controls (zona-intact oocytes with 1000 spermatozoa/oocyte), indicating that ZPs
      of in vitro matured pig oocytes failed to block polyspermy during in vitro
      fertilization. (2) In vitro development of zygotes from ZP-free oocytes showed
      that there was no difference in cleavage rates. The blastocyst rate was slightly
      lower in the ZP-free group than the control. However, there was no difference in
      cell number per blastocyst between the control and the ZP-free group. (3)
      Examination of acrosome status by a specific fluorescein isothiocyanate
      conjugated peanut agglutinin (FITC-PNA) staining procedure revealed that frozen
      thawed pig spermatozoa could undergo acrosome reaction and penetrate oocytes
      without induction by ZP. These data suggested that there are alternative
      mechanistic pathways for acrosome reaction induction during the fertilization
      process than the widely accepted sperm-zona receptor models. Finally, the
      viability of ZP-free derived embryos was demonstrated by full-term development
      and the delivery of healthy piglets following embryo transfer. In conclusion, the
      present experiments showed for the first time in farm animals, that normal
      embryos could be produced by in vitro fertilization of ZP-free oocytes in
      optimized conditions and that they could develop normally to full-term.

PMID- 15451266
TI  - The lives we touch.

PMID- 15451263
TI  - Oral intake of shark liver oil modifies lipid composition and improves motility
      and velocity of boar sperm.
AB  - The natural ether-lipids 1-O-alkylglycerols (alkyl-Gro) from shark liver oil
      improve boar sperm motility and fertility in vitro. We examined the effects of
      oral shark liver oil on motility and velocity parameters of sperm together with
      modifications of lipid composition. Eleven boars were used as control and 11 were
      fed with 40 g/day for 28 days and sperm was collected on Days 0, 14 and 28 in
      control and treated groups. After 28 days treatment, sperm motility was improved
      by 2.9% as well as velocity parameters (curvilinear velocity +10.75%, progressive
      velocity +18.8% and average path velocity +13.5%) and sperm lipid composition was
      modified as follows: alkyl-Gro with saturated chains were increased (C16:0
      +40.1%, C18:0 +87.2%) while alkyl-Gro with unsaturated chains remained absent, as
      in the control group, despite the prominence of C18:1 and C16:1 in shark liver
      oil. The treatment also resulted in an overall increase in the proportion of n -
      3 and n - 6 polyunsaturated fatty acids in sperm lipids with a prominent increase
      of docosahexaenoic acid over time (18.9 +/- 1.34% at Day 0 to 25.7 +/- 1.11% at
      Day 28) and compared to control (25.7 +/- 1.11% for treated versus 16.1 +6/- 0.81
      % for control at Day 28, respectively). These data demonstrate the influence of
      lipid intake on boar sperm composition and functions and suggest that oral intake
      of shark liver oil might improve reproduction.

PMID- 15451267
TI  - Spinal canal size in ossification of the posterior longitudinal ligament of the
      cervical spine.
AB  - BACKGROUND: The size of the spinal canal is a factor that contributes to the
      neurologic deficits associated with cervical ossification of the posterior
      longitudinal ligament (OPLL). METHODS: Bone-window computed tomography (CT)
      examinations of the cervical spine in 64 patients with cervical OPLL were
      reviewed. Forty-two patients underwent surgical treatment (anterior
      decompression: 16 patients, posterior decompression: 26 patients). The remaining
      22 patients were managed conservatively. Selection of the surgical approach,
      anterior or posterior, was based on the longitudinal extent of cord compression.
      RESULTS: The mean developmental size of the spinal canal in the posterior
      decompression group (10.7 mm at C4) was significantly smaller than the other 2
      groups. The spinal canal was narrowed by OPLL to 2.9 to 10.0 mm. The proportion
      of the patients showing motor deficits of the lower extremities significantly
      increased when the sagittal canal diameter was narrowed to less than 8 mm.
      CONCLUSIONS: This study demonstrates critical values of CT-determined spinal
      canal stenosis. Developmental size of the spinal canal and the residual anterior
      posterior canal diameters resulting from OPLL spinal cord compression are
      important factors influencing clinical management and the neurologic state.

PMID- 15451269
TI  - Contribution of angiotensin-converting enzyme and angiotensin II to ischemic
      stroke: their role in the formation of stable and unstable carotid
      atherosclerotic plaques.
AB  - BACKGROUND: The angiotensin-converting enzyme/angiotensin II (ACE/Ang II) system
      is a strong contributor to intimal hyperplasia in atherosclerotic lesions. To
      illuminate its role in ischemic stroke, we examined the expression of ACE/Ang II
      in stable and unstable carotid atherosclerotic plaques from symptomatic and
      asymptomatic patients. METHODS: Using immunohistochemical methods, we studied
      differences between carotid atherosclerotic lesions obtained at carotid
      endarterectomy (CEA) from symptomatic (n = 36) and asymptomatic (n = 28)
      patients. The specimens were classified as stable (n = 30) and unstable (n = 34)
      plaques, and their fibrous cap, lipid core, and shoulder lesion were examined. We
      used antibodies against smooth muscle cells (SMC), macrophages, endothelial cells
      (EC), ACE, and Ang II. RESULTS: Of 28 lesions from asymptomatic patients, 20
      (71.4%) manifested features characteristic of stable plaques: the expression of
      ACE/Ang II co-localized with SMC, EC, and macrophages in the shoulder lesion. In
      contrast, 26 of 36 symptomatic lesions (72.2%) exhibited the typical features of
      unstable plaques: dense accumulations of macrophages near the luminal surface in
      the shoulder lesion and weak immunoreactivity for ACE/Ang II, EC, and SMC.
      Furthermore, most of the lesions were accompanied by early stage atherosclerotic
      lesions (satellite lesions) that were strongly immunoreactive with macrophages,
      EC, and ACE/Ang II. CONCLUSIONS: ACE/Ang II expression may induce the
      proliferation of SMC and EC and result in the formation of carotid
      atherosclerotic plaques with a thick fibrous cap. Notably, the shoulder lesion of
      unstable plaques exhibited a thin fibrous cap and faintly expressed ACE/Ang II.
      Lack of the ACE/Ang II system may contribute to the final step in plaque rupture.

PMID- 15451272
TI  - Intravenous abciximab for parent vessel thrombus during basilar apex aneurysm
      coil embolization: case report and literature review.
AB  - BACKGROUND: Parent vessel thrombus formation is a serious complication of
      intracranial aneurysm embolization. The management of this issue is
      controversial. Abciximab, a potent platelet inhibitor, has been shown to have
      thrombolytic effects during coronary interventions. A small number of cases have
      demonstrated its potential application in neuroendovascular procedures. We review
      the literature on the management of parent vessel thrombosis during aneurysm coil
      embolization and report our successful experience with the use of IV abciximab to
      treat parent vessel thrombus formation related to coil embolization of a basilar
      apex aneurysm. CASE DESCRIPTION: A 45-year-old man presented to our center with
      an incidental basilar apex aneurysm. After being informed of the surgical and
      endovascular treatment options, he elected to undergo coil embolization of the
      aneurysm. During the procedure, acute thrombus was noted in the left P1 segment
      of the posterior cerebral artery. IV abciximab was administered, and an angiogram
      the following day showed complete dissolution of the clot. The patient had no
      neurologic sequelae. CONCLUSIONS: IV abciximab appears to be an effective option
      in the management of acute parent vessel thrombus encountered during coil
      embolization of unruptured aneurysms. Sufficient data are lacking regarding its
      use in the setting of a ruptured aneurysm.

PMID- 15451273
TI  - Cerebral blood oxygenation after cerebrospinal fluid removal in hydrocephalus
      measured by near infrared spectroscopy.
AB  - BACKGROUND: The cerebrospinal fluid (CSF) tap test has been used for the
      diagnosis of chronic hydrocephalus to identify the candidates for surgical CSF
      shunting. However, a high rate of false negative results limits it utility. The
      purpose of this study is to investigate whether the concomitant monitoring of
      cerebral hemodynamics by near infrared spectroscopy (NIRS) can improve the
      diagnostic accuracy of the tap test. METHODS: Thirteen patients with dilated
      ventricular system were candidates for this study. We assessed for the patterns
      of cerebral blood oxygenation (CBO) change in hydrocephalus to determine whether
      CBO change after CSF removal is useful for selecting shunt candidates. RESULTS:
      Patients who showed clinical improvement following CSF shunting had a
      characteristic CBO change with increases in the concentration of oxyhemoglobin
      (Oxy-Hb), and patients without improvement during continuous CSF drainage test
      showed no increase in Oxy-Hb. CONCLUSION: The current data suggests that CBF
      increases after CSF removal in hydrocephalus. Although the patients utilized in
      the present study had secondary chronic hydrocephalus, we speculate that these
      data could be applied to patients with idiopathic chronic hydrocephalus. Further
      investigation would be of benefit.

PMID- 15451275
TI  - Intracerebral hemorrhage after carotid endarterectomy associated with
      asymptomatic perioperative cerebral ischemia detected by cerebral perfusion
      imaging: case report.
AB  - BACKGROUND: Risk factors for intracerebral hemorrhage following carotid
      endarterectomy (CEA) include perioperative cerebral ischemia, postoperative
      cerebral hyperperfusion, and postoperative anticoagulation therapy, and at least
      2 of these risk factors are typically present in the context of intracerebral
      hemorrhage (ICH). CASE DESCRIPTION: A 75-year-old man with severe bilateral
      cervical internal carotid artery stenosis and a minor stroke resulting in left
      motor weakness underwent a right CEA. The operation was uneventful, and the
      patient did not experience new neurologic deficits upon recovery from anesthesia.
      Brain single photon emission computed tomography (SPECT) obtained immediately
      after CEA showed a perfusion defect in the right parietal lobe and absence of
      cerebral hyperperfusion. A computed tomography (CT) scan showed no new abnormal
      findings. Aspirin therapy was instituted postoperatively. On the second
      postoperative day, the patient experienced abrupt worsening of left hemiparesis,
      and subsequent CT imaging demonstrated a hematoma in the right parietal lobe.
      Cerebral hyperperfusion was absent on repeat SPECT. CONCLUSION: Perioperative
      cerebral ischemia can result in intracerebral hemorrhage after CEA even in the
      absence of cerebral hyperperfusion and/or anticoagulation therapy. Further,
      cerebral perfusion imaging performed immediately after CEA is a useful modality
      for the identification of occult cerebral ischemia or hyperperfusion that may
      lead to intracerebral hemorrhage.

PMID- 15451278
TI  - Recurrence of cerebral arteriovenous malformations in children: report of two
      cases and review of the literature.
AB  - BACKGROUND: Angiography is considered the standard to assess the treatment
      success of cerebral arteriovenous malformations (AVMs). When postoperative
      angiograms show neither residual nidus nor early draining veins, patients are
      considered cured, and the risks of hemorrhage are eliminated. However, this
      notion is challenged by the development of recurrent AVMs in children. In our
      report, 2 children developed recurrent AVMs after undergoing complete resection,
      which was documented by postoperative angiography. We review other similar cases
      reported in the literature to help establish guidelines for postoperative
      monitoring. METHODS: In this retrospective review, 36 children underwent complete
      surgical resection of cerebral AVMs that were documented by intra- or
      postoperative angiography. After a follow-up period ranging from 1 to 17 years,
      rates of recurrence were assessed. RESULTS: Although angiographic documentation
      showed complete resection, 2 children developed recurrences 3 and 5 years later.
      Among these 36 children, the recurrence rate was 5.5% at follow-up (mean 9
      years). CONCLUSIONS: Based on our data and review of the literature, intra- or
      early postoperative angiography is essential to exclude the presence of a
      residual nidus but does not ensure cure of the AVMs in children. If postoperative
      angiographic scans are obtained too early, postoperative changes may prevent the
      detection of a residual nidus. Therefore, we recommend that angiographic scans be
      obtained intraoperatively or early postoperatively to document complete resection
      and again at 1 and 5 years after surgical resection.

PMID- 15451280
TI  - Conventional posterior fossa approach for surgery on petroclival meningiomas: a
      report on an experience with 28 cases.
AB  - BACKGROUND: This is a report of our experience with 28 cases of select
      petroclival meningiomas operated by a posterior fossa route encompassing the
      lateral supracerebellar-infratentorial and retrosigmoid avenues. METHODS: Twenty
      eight cases of petroclival meningiomas treated during the period 1991 to 2002 by
      conventional posterior cranial fossa route are analyzed. The average length of
      follow-up is 48 months. RESULTS: The maximum diameter of the tumors ranged from
      1.8 to 6.8 cm (mean, 4.0 cm). Five tumors extended up to or beyond the
      contralateral petroclival junction. Basilar artery was at least partially encased
      in 9 cases. Gross total tumor resection was achieved in 21 cases and a partial
      tumor resection was achieved in the remaining 7 cases. Two patients died in the
      postoperative phase. CONCLUSIONS: Conventional posterior cranial fossa surgery
      can be suitable for a select group of petroclival meningioma. Apart from other
      advantages, it provides easy and quick exposure of the tumor without any petrous
      bone drilling. It also provides a direct and early exposure of the tumor-cranial
      nerve-brainstem interface facilitating the dissection. The lateral and inferior
      tumor extensions in relationship to the clivus can be more easily accessed. The
      site of attachment of the tumor to the dura overlying the posterior face of the
      petrous apex can be seen directly.

PMID- 15451285
TI  - Rapid cognitive decline following lumbar puncture in a patient with a dural
      arteriovenous fistula.
AB  - BACKGROUND: Dural arteriovenous fistulas (DAVFs) are frequently accompanied with
      raised intracranial pressure and clinical findings suggestive of pseudotumor
      cerebri. However, unlike pseudotumor cerebri, the clinical response to lumbar
      cerebrospinal fluid (CSF) removal can vary from beneficial to acute clinical
      deterioration leading to death. The criteria for the safe use of lumbar puncture
      (LP) in patients with a DAVF are not well established. METHODS: A 61-year-old man
      presented with visual difficulty. Magnetic resonance imaging (MRI) and
      angiography revealed a left transverse sinus DAVF. He underwent multiple
      embolizations of arterial feeders over 3 years. He was then noted to have
      cognitive deficits in short term memory, listening, and concentrating. Over
      several days after an LP he became increasingly lethargic but arousable. Within
      hours after a repeat LP there was a rapid deterioration in the patient's level of
      consciousness and he became unarousable. RESULTS: A brain MRI revealed extensive
      dilated cortical veins and left temporal lobe venous ischemia without tonsillar
      herniation. A cerebral angiogram showed an extensive left transverse sinus DAVF
      with an occluded lateral transverse sinus and increased retrograde venous
      drainage. Embolization of the arterial feeders in combination with trans-venous
      coil embolization of the left transverse sinus reversed the patient's neurologic
      decline. He was discharged neurologically intact except for his chronic visual
      acuity problems. CONCLUSION: We speculate that when a DAVF manifests retrograde
      venous flow sufficient to cause cognitive deficits, lumbar CSF drainage must be
      undertaken with extreme caution.

PMID- 15451288
TI  - Ruptured de novo thrombotic giant aneurysm induced by ethyl 2-cyanoacrylate: case
      report.
AB  - BACKGROUND: A very rare case of a ruptured aneurysm induced by ethyl 2
      cyanoacrylate is reported. CASE DESCRIPTION: Six years earlier, this 68-year-old
      woman had undergone microvascular decompression for trigeminal neuralgia during
      which the left vertebral artery, which compressed the exit zone of the trigeminal
      nerve, had been detached and fixed to the dura mater of the petrous bone with
      ethyl 2-cyanoacrylate. Shortly thereafter she underwent microvascular
      decompression for left-side facial palsy; again ethyl 2-cyanoacrylate was used.
      Six years later, she suffered a subarachnoid hemorrhage because of rupture of a
      new aneurysm of the left vertebral artery. She was referred to our hospital where
      coil embolization was attempted on the day following the insult. However, the
      left vertebral artery and the aneurysm could not be occluded completely, and she
      suddenly died 20 days later from rerupture of the aneurysm. CONCLUSION: This is
      the first pathologic report of a ruptured de novo aneurysm induced by ethyl 2
      cyanoacrylate. We suggest that arterial wall damage by ethyl 2-cyanoacrylate may
      have contributed to the development of the de novo aneurysm.

PMID- 15451291
TI  - Management of patients with schwannomatosis: report of six cases and review of
      the literature.
AB  - BACKGROUND: Schwannomatosis is a rare tumor syndrome characterized by the
      presence of multiple schwannomas without the stigmata of neurofibromatosis (NF)
      Type 1 or 2. To better understand the natural history and clinical management of
      the syndrome, a retrospective review was conducted of patients diagnosed with
      schwannomatosis over an 11-year period at the University of Pennsylvania Medical
      Center (UPMC). METHODS: Between 1990 and 2001, 131 patients underwent surgery for
      resection of spinal or peripheral nerve schwannomas in the Department of
      Neurosurgery at the University of Pennsylvania Medical Center. Among the 131
      patients, there were 6 who had two or more pathologically proven schwannomas
      without radiographic or clinical evidence of vestibular schwannomas. The hospital
      charts, clinic notes, radiology films, operative reports, pathology slides, and
      reports from all 6 patients were retrospectively reviewed. RESULTS: The patient
      population consisted of 6 patients with a mean age of 48.7 (3 male: 3 female).
      All patients had enhanced brain magnetic resonance imaging (MRI) scans that were
      negative for vestibular schwannomas. Ophthalmological and general physical
      examinations did not reveal any findings suggestive of NF. There was no family
      history of NF or schwannomatosis. The locations of the schwannomas included
      intraspinal (multiple sites), paraspinal, brachial plexus, femoral nerve, sciatic
      nerve, calf, forearm, retroperitoneum, and middle cranial/infratemporal fossa
      region. The common presenting symptoms included paresthesias, palpable mass,
      pain, or weakness. All 6 patients underwent surgical resection of symptomatic
      lesions. CONCLUSIONS: For patients with schwannomatosis, surgery is indicated for
      symptomatic lesions, while asymptomatic tumors are followed conservatively.
      Because these patients are at increased risk for developing multiple schwannomas,
      we recommend regular surveillance and offer genetic counseling even though the
      pattern of inheritance is unknown.

PMID- 15451293
TI  - Massive intracerebral air embolism associated with meningitis and lumbar
      spondylitis: case report.
AB  - BACKGROUND: Massive intracerebral air embolism is a rare pathologic state and
      never in association with meningitis and lumbar spondylitis. To the best of our
      knowledge, our presented case is the first of a massive intracerebral air
      embolism associated with meningitis and lumbar spondylitis of Klebsiella
      pneumonia. CASE DESCRIPTION: A 55-year-old man presented with a high fever and
      low back pain. Blood culture showed Klebsiella pneumonia. Lumbar computed
      tomography (CT) revealed discitis at L1-2 and L2-3 levels and paraspinal abscess
      in which air was found. Despite management with antibiotics, patient's
      consciousness deteriorated, and brain CT revealed diffuse intravenous air
      embolism and severe brain swelling. Cerebrospinal fluid (CSF) examination
      demonstrated bacterial meningitis, and the CSF culture showed Klebsiella
      pneumonia. Later, septic shock occurred and patient expired. CONCLUSION:
      Intracerebral air embolism can occur in the Klebsiella pneumonia meningitis that
      resulted from lumbar spondylitis and sepsis.

PMID- 15451295
TI  - A simple surgical technique of direct anastomosis for treatment of moyamoya
      disease: technical note.
AB  - BACKGROUND: An arteriotomy on a branch of the middle cerebral artery (MCA) is
      required in the procedure of the direct anastomosis for the treatment of moyamoya
      disease, and the artery comes to be collapsed after blood is washed out. The
      phenomenon makes the microsurgical procedure difficult during direct anastomosis.
      METHODS: A piece of 3-0 blue monofilament polypropylene suture (PROLENE*, ETHICON
      Inc., a Johnson & Johnson Company, Somerville, New Jersey) was inserted into the
      lumen of the recipient artery though the ostium after termination of arteriotomy.
      The diameter of 3-0 PROLENE* was between 0.20 and 0.249 mm. PROLENE*, a length
      that was more than the length of the arteriotomy and was less than the distance
      between the 2 occlusion clamps placed on the recipient artery. At this time, the
      lumen was reopened and the wall of the recipient artery was easily passed by a
      microneedle with 11-0 monofilament without injury to the posterior wall of the
      recipient artery by the microneedle. Confirmation as to whether the microneedle
      snagged and injured the posterior wall of the recipient artery or not was
      unnecessary with this method. RESULTS: Anastomosis was easily performed using
      this technique for the treatment of moyamoya disease. CONCLUSIONS: Clinical
      application of the present technique makes the anastomotic procedure easy, even
      when the diameter of the recipient artery is as small as 0.5 mm.

PMID- 15451296
TI  - Down with "health plans"!

PMID- 15451297
TI  - The era of credit card medicine.

PMID- 15451298
TI  - Re: An institution par excellence: Prof. B. Ramamurthi 1922-2003. Surg neurol
      2004;61:511-14.

PMID- 15451299
TI  - Re: Surgical management of brachial plexus region tumors. Surg Neurol 2004;61:372
      8.

PMID- 15451302
TI  - Inhibitory effect of Daesungki-Tang on the invasiveness potential of
      hepatocellular carcinoma through inhibition of matrix metalloproteinase-2 and -9
      activities.
AB  - Daesungki-Tang (DST), a drug preparation consisting of four herbs, that is, Rhei
      radix et rhizoma (RR; the roots of Rheum coreanum Nakai, Daehwang in Korean),
      Aurantiii frutus immaturus (AFI; immature fruits of Poncirus trifolita Rafin.,
      Jisil in Korean), Magnoliae cortex (MC; the stem bark of Magnolia officinalis
      Rehd. Et Wils., Hubak in Korean), and Mirabilite (MS; Matrii sulfas, Mangcho in
      Korean), is a traditional Korean herbal medicine that is widely used in the
      treatment of cancer metastasis, gastrointestinal complaints, vascular disorders,
      and atherosclerosis-related disorders. In this study, water extracts of DST and
      each of the four ingredient herbs were prepared. The extracts were tested for
      cytotoxic activity on human hepatocellular carcinoma cells, Hep3B cells using the
      XTT assay method. The inhibitory effect of the extracts on the invasion of Hep3B
      cells was also tested using matrigel precoated transwell chambers. DST
      effectively inhibited the invasion of Hep3B cells, compared with the control
      groups in a dose-dependent manner. In addition, a gelatin zymography assay showed
      that DST decreased the gelatinolytic activity of matrix metalloproteinases-2 (MMP
      2; IC50 = 87 microg/ml) and -9 (MMP-9; IC50 = 75 microg/ml) that are secreted
      from Hep3B cells, respectively. Among the four herbal ingredients of DST, only MC
      has been shown to significantly inhibit the invasion of Hep3B cells and MMP-2 and
      -9 activities. From these results, it can be concluded that DST has some
      potential for use as an antitumor agent.

PMID- 15451303
TI  - Mechanism of differential inhibition of hepatic and pancreatic fatty acid ethyl
      ester synthase by inhibitors of serine-esterases: in vitro and cell culture
      studies.
AB  - Earlier, we have shown that rat hepatic and pancreatic fatty acid ethyl ester
      (FAEE) synthases are structurally and functionally similar to rat liver
      carboxylesterase (CE) and pancreatic cholesterol esterase (ChE), respectively. We
      have also reported that only hepatic FAEE synthase is inhibited by tri-o
      tolylphosphate (TOTP) in vivo and in human hepatocellular carcinoma (HepG2)
      cells. The metabolism of TOTP is a prerequisite for the inhibition of hepatic
      FAEE synthase as well as esterase activity. To further elucidate the mechanism of
      such differential inhibition by inhibitors of serine esterases, we synthesized
      two metabolites of TOTP, 2-(o-cresyl)-4H-1:3:2-benzodioxaphosphoran-2-one (CBDP;
      cyclic saligenin phosphate) and di-o-tolyl-o-( proportional, variant 
      hydroxy)tolylphosphate (HO-TOTP), and one ChE inhibitor, 3-benzyl-6-chloro-2
      pyrone (3-BCP). The inhibitory effect of CBDP, HO-TOTP, and 3-BCP on FAEE
      synthase and esterase activity was studied using rat hepatic and pancreatic
      postnuclear (PN) fractions, commercial porcine hepatic CE and pancreatic ChE, and
      in HepG2 and rat pancreatic tumor (AR42J) cell lines. Only HO-TOTP and CBDP
      inhibited FAEE synthase as well as esterase activity of hepatic PN fraction and
      commercial CE and ChE in a concentration-dependent manner, and the inhibition was
      found to be irreversible. However, no inhibition was found in pancreatic PN
      fraction by both TOTP metabolites and 3-BCP. Although 3-BCP inhibited only the
      esterase activity of commercial ChE in a concentration-dependent manner, the
      activity was reversible within 30 min of incubation. Studies with HepG2 cells
      also showed a significant inhibition of FAEE synthase-esterase activity by CBDP
      and HO-TOTP within 15 min of incubation, while no inhibition was observed in
      AR42J cells. 3-BCP did not inhibit FAEE synthase-esterase activity either in
      HepG2 or AR42J cells. Such differential inhibitory effect of the TOTP metabolites
      on hepatic and pancreatic FAEE synthase-esterase is supported by our earlier in
      vivo and in vitro studies. Further investigations are needed to understand the
      biochemical mechanism(s) of inactivation of TOTP metabolites and 3-BCP in the
      pancreas and AR42J cells towards FAEE synthase-esterase activities.

PMID- 15451304
TI  - Quantitative gene expression analysis in a nonhuman primate model of antibiotic
      induced nephrotoxicity.
AB  - Gene expression patterns using microarrays have been described for rodent models
      of nephrotoxicity. To determine if significant gene expression changes previously
      identified have application across multiple species, we studied quantitative gene
      expression changes in the kidneys of female cynomolgus monkeys after exposure to
      two nephrotoxicants. Animals were dosed with the aminoglycoside gentamicin (10
      mg/kg), the experimental oligosaccharide antibiotic everninomicin (30 or 60
      mg/kg), or a combination of gentamicin (10 mg/kg) and everninomicin (30 mg/kg)
      for 7 days. Monkeys receiving these drugs in combination developed renal lesions
      as early as Day 1. By Day 7, monkeys dosed with 60 mg/kg everninomicin alone also
      developed renal lesions, while the group exposed to both compounds had more
      extensive renal damage. The modulation of several genes previously reported to be
      associated with nephrotoxicity in rodent models was confirmed using quantitative
      real-time PCR. Among these, waf-1, matrix metalloproteinase-9, and vimentin
      exhibited changes consistent with the definition of a genomic indicator of
      toxicity. In addition, we identified three early gene biomarkers that may be
      predictive of drug-induced nephrotoxicity: clusterin, osteopontin, and hepatitis
      A virus cellular receptor-1. Logistic regression demonstrated a high degree of
      correlation between changes in gene expression and the probability of the
      development of histopathologic lesions. These results are the first confirming
      rodent gene expression changes associated with nephrotoxicity in a nonhuman
      primate model and provide preliminary evidence for identifying early gene
      expression changes predicting the onset of drug-induced renal tubular damage in
      cynomolgus monkeys.

PMID- 15451305
TI  - Lead (Pb(+2)) impairs long-term memory and blocks learning-induced increases in
      hippocampal protein kinase C activity.
AB  - The long-term storage of information in the brain known as long-term memory (LTM)
      depends on a variety of intracellular signaling cascades utilizing calcium (Ca2+)
      and cyclic adenosine monophosphate as second messengers. In particular,
      Ca(+2)/phospholipid-dependent protein kinase C (PKC) activity has been proposed
      to be necessary for the transition from short-term memory to LTM. Because the
      neurobehavioral toxicity of lead (Pb(+2)) has been associated to its interference
      with normal Ca(+2) signaling in neurons, we studied its effects on spatial
      learning and memory using a hippocampal-dependent discrimination task. Adult rats
      received microinfusions of either Na+ or Pb(+2) acetate in the CA1 hippocampal
      subregion before each one of four training sessions. A retention test was given 7
      days later to examine LTM. Results suggest that intrahippocampal Pb(+2) did not
      affect learning of the task, but significantly impaired retention. The effects of
      Pb(+2) selectively impaired reference memory measured in the retention test, but
      had no effect on the general performance because it did not affect the latency to
      complete the task during the test. Finally, we examined the effects of Pb(+2) on
      the induction of hippocampal Ca(+2)/phospholipid-dependent PKC activity during
      acquisition training. The results showed that Pb(+2) interfered with the learning
      induced activation of Ca(+2)/phospholipid-dependent PKC on day 3 of acquisition.
      Overall, our results indicate that Pb(+2) causes cognitive impairments in adult
      rats and that such effects might be subserved by interference with Ca(+2)-related
      signaling mechanisms required for normal LTM.

PMID- 15451306
TI  - Reduced sulfur mustard-induced skin toxicity in cyclooxygenase-2 knockout and
      celecoxib-treated mice.
AB  - Sulfur mustard (SM), a potent vesicant and chemical warfare agent, induces tissue
      damage involving an inflammatory response, including vasodilatation,
      polymorphonuclear infiltration, production of inflammatory mediators, and
      cyclooxygenase activity. To evaluate the role of cyclooxygenase-1 and -2 (COX-1,
      COX-2) in sulfur mustard-induced skin toxicity, we applied the agent to the ears
      of wildtype (WT) and COX-1- and COX-2-deficient mice. In the latter, ear swelling
      24 and 48 h after exposure was significantly reduced (P < 0.05) by 55% and 30%,
      respectively, compared to WT. Quantitative histopathology revealed no epidermal
      ulceration in COX-2-deficient mice but some degree of severity in WT. COX-2
      deficient mice showed significant reductions (P < 0.05) in severity of epidermal
      necrosis (29%), acute inflammation (42%), and hemorrhage (25%), compared to the
      WT mice. COX-1 deficiency resulted in significant exacerbation (P < 0.05) in
      severity of some parameters, including increases of 4.6- and 1.2-fold in
      epidermal ulceration and epidermal necrosis, respectively, compared to WT.
      Postexposure treatment of normal male ICR mice with the selective COX-2 inhibitor
      celecoxib resulted in significant reductions of 27% (P < 0.05) and 28% (P < 0.01)
      in ear swelling at intervals of 40 and 60 min between exposure and treatment,
      respectively. Histopathological evaluation revealed significant reductions (P <
      0.05) in subepidermal microblister formation (73%) and dermal necrosis (32%),
      compared to the control group. These findings may indicate that COX-2
      participates in the early stages of sulfur mustard-induced acute skin toxicity
      and that COX-1 might exert some protective function against this chemical insult.

PMID- 15451307
TI  - Endogenous tissue type plasminogen activator facilitates NMDA-induced retinal
      damage.
AB  - To investigate the role of tissue plasminogen activator (tPA) in retinal damage,
      tPA-deficient and wild-type mice were employed. Two different retinal neuron
      insult models were used in the present study. One is an excitotoxin-treated
      retinal model, created by direct intravitreal injection of glutamate analogs,
      NMDA or kainic acid (KA), and the other is an ischemia-reperfusion model induced
      by transient elevation of intraocular pressure. TdT-dUTP terminal nick-end
      labeling (TUNEL) method was used to examine the retinal cell nuclear damage. The
      number of TUNEL-positive cells in ganglion cell layer (GCL) and inner nuclear
      layer (INL) in tPA-deficient mice after low-, but not high-dose NMDA was
      significantly less compared to wild type. In contrast, neither intravitreal KA or
      transient ischemia produced significant difference in retinal damage in tPA vs.
      wild-type mice. These data show that tPA-deficient mice are resistant to retinal
      damage by intravitreal injection of NMDA, and indicate that tPA plays a role in
      the retinal cell damage induced by excitotoxins, especially NMDA.

PMID- 15451308
TI  - The effect of developmental exposure to the fungicide triadimefon on behavioral
      sensitization to triadimefon during adulthood.
AB  - Triadimefon (TDF) is a triazole fungicide that acts as an indirect dopamine (DA)
      agonist by binding to the dopamine transporter (DAT) and increasing levels of
      synaptic DA. Studies in this laboratory have found that repeated dosing with TDF
      in adult mice leads to the development and robust expression of behavioral
      sensitization, a response mediated by dopaminergic and glutamatergic
      neurotransmitter systems, and causing long-term changes in dopaminergic function.
      Few studies have focused on the potential for TDF to be a developmental
      neurotoxicant. As such, the objective of the present study was to determine
      whether postnatal exposure to TDF would permanently alter DA systems and thereby
      influence TDF-induced expression of behavioral sensitization during adulthood.
      Male C57BL/6 mice were dosed intraperitoneally (i.p.) with 25 mg/kg TDF (TDF25),
      or oil (veh) from postnatal day (PND) 8 to 21. At 8-9 weeks of age, mice were
      split into four groups and treated with 75 mg/kg TDF (TDF75) or vehicle twice a
      week for a total of seven injections, with locomotor activity measured
      immediately after each injection. After a 2-week withdrawal period, mice were
      further split into eight groups, and challenged with TDF75 or vehicle to test for
      the expression of behavioral sensitization. Postnatal TDF exposure attenuated
      both the induction and expression of TDF-induced vertical but not horizontal
      sensitization in adults. Postnatal TDF exposure also produced long-term decreases
      in basal striatal dihydroxyphenylacetic acid (DOPAC) levels and nucleus accumbens
      shell DAT binding. These results indicate for the first time that TDF may be
      considered an environmental risk factor for developmental dopaminergic
      neurotoxicity.

PMID- 15451309
TI  - In vitro cytotoxic and genotoxic effects of diphenylarsinic acid, a degradation
      product of chemical warfare agents.
AB  - Diphenylarsinic acid [DPAs(V)], a degradation product of diphenylcyanoarsine or
      diphenylchloroarsine, both of which were developed as chemical warfare agents,
      was investigated in terms of its capacity to induce cytotoxic effects, numerical
      and structural changes of chromosomes, and abnormalities of centrosome integrity
      and spindle organizations in conjunction with the effects of glutathione (GSH)
      depletion. DPAs(V) had toxic effects on cultured human hepatocarcinoma HepG2
      cells at concentrations more than 0.5 mM. Depletion of GSH reduced the toxic
      effects of DPAs(V) as well as dimethylarsinic acid [DMAs(V)] toxicity, while
      toxicity by arsenite [iAs(III)] was enhanced. Exogenously added sulfhydryl (SH)
      compounds, such as dimercapropropane sulfonate (DMPS), GSH, and dithiothreitol
      (DTT), enhanced the toxic effects of DPAs(V) while they suppressed iAs(III)
      toxicity. DPAs(V) caused an increase in the mitotic index, and also structural
      and numerical changes in chromosomes in V79 Chinese hamster cells. Abnormality of
      centrosome integrity in mitotic V79 cells and multipolar spindles was also
      induced by DPAs(V) in a time- and concentration-dependent manner. These results
      suggested that highly toxic chemicals were generated by the interaction of
      DPAs(V) with SH compounds. Moreover, enhancements of toxicity by a combination of
      DPAs(V) and SH compounds suggested a risk in the use of SH compounds as a remedy
      for intoxication by diphenylarsenic compounds. Investigations on the effects of
      SH compounds on animals intoxicated with DPAs(V) are warranted.

PMID- 15451310
TI  - Effects of vehicle on the uptake and elimination kinetics of capsaicinoids in
      human skin in vivo.
AB  - While the physiologic and molecular effects of capsaicinoids have been
      extensively studied in various model systems by a variety of administration
      routes, little is known about the uptake and elimination kinetic profiles in
      human skin following topical exposure. The present study evaluated the uptake and
      elimination kinetics of capsaicinoids in human stratum corneum following a single
      topical exposure to 3% solutions containing 55% capsaicin, 35% dihydrocapsaicin,
      and 10% other analogues prepared in three vehicles: mineral oil (MO), propylene
      glycol (PG), and isopropyl alcohol (IPA). Capsaicinoid solutions were evaluated
      simultaneously in a random application pattern on the volar forearms of 12
      subjects using a small, single 150-microg dose. Capsaicin and dihydrocapsaicin
      were recovered from human skin using commercial adhesive discs to harvest stratum
      corneum from treated sites. Capsaicinoids were extracted from the stratum corneum
      adhesive discs and quantified by liquid chromatography/mass spectroscopy (LC/MS).
      Both capsaicinoids were detected in stratum corneum 1 min after application with
      all vehicles and achieved a pseudo-steady state shortly thereafter. IPA delivered
      three times greater capsaicin and dihydrocapsaicin into the human stratum corneum
      than PG or MO at all time points investigated. The Cmax of capsaicin in IPA, PG,
      and MO was 16.1, 6.2, and 6.5 microg, respectively. The dihydrocapsaicin content
      was 60% of capsaicin with all vehicles. The estimated T(half) of capsaicin and
      dihydrocapsaicin in the three vehicles was similar (24 h). Thus, maximal
      cutaneous capsaicinoid concentrations were achieved quickly in the human stratum
      corneum and were concentration and vehicle dependent. In contrast, capsaicinoid
      half-life was long and vehicle independent.

PMID- 15451311
TI  - Halogenated diterpenoids from the red alga Laurencia nipponica.
AB  - Chemical compositions of three collections of the red alga Laurencia nipponica
      from the western part of the Sea of Japan were studied. One of them contained a
      series of the previously known sesquiterpenoids. Another one gave C15 bromoallene
      ethers, predominantly. Finally, two new halogenated diterpenes, 15-bromoparguer
      9(11)-ene-16-ol and 15-bromoparguer-7-ene-16-ol, were isolated from the third
      collection of the same species. Structures of these diterpenoids were established
      by 1D and 2D NMR (1H-1H COSY, DEPT, HMQC, HMBC and NOESY) along with molecular
      calculations for conformations having lowest energies and mass spectroscopy.
      Diversity and variability of halogenated secondary metabolites in L. nipponica
      were discussed.

PMID- 15451312
TI  - Clerodane-type diterpenoids from Nannoglottis ravida.
AB  - Chemical investigation of the roots of Nannoglottis ravida resulted in the
      characterization of two 5alpha,10alpha-cis-clerodane-type diterpenoides, ravidin
      A and B. Their structures and stereochemistry were established by spectroscopic
      methods, including X-ray crystallographic diffraction analysis of ravidin A.
      Their significance in terms of the chemotaxonomy of Nannoglottis is discussed.

PMID- 15451313
TI  - Nor-ent-kaurane diterpenes and hydroxylactones from Antennaria geyeri and
      Anaphalis margaritacea.
AB  - In a study of Pacific Northwest plants of the Asteraceae family, a nor-ent
      kaurane diterpene and a known diterpene, both displaying antibacterial
      activities, were isolated together with scopoletin and sitosterol-3-O-beta
      glucopyranoside from the aerial parts of Antennaria geyeri. Anaphalis
      margaritacea afforded two hydroxylactones. The structures were established by one
      and two dimensional NMR techniques, IR and CIMS.

PMID- 15451314
TI  - Two lanostane triterpenoids from Abies koreana.
AB  - Two lanostane-type triterpenoids, namely, 24(E)-3,4-seco-9betaH-lanosta
      4(28),7,24-triene-3,26-dioic acid and 24(E)-3-oxo-9betaH-lanosta-7,24-dien-26-ol
      were isolated from the root bark of Abies koreana. Their structures were
      established based on spectroscopic analyses. Compound 2 exhibited marginal
      cytotoxicity against human tumor cell lines.

PMID- 15451315
TI  - Dendrocyin: an isocucurbitacin with novel cyclic side chain from Dendrosicyos
      socotrana.
AB  - Dendrosicyos socotrana Balf.f. is a unique species (Cucurbitaceae) native to
      Socotra island in the horn of Africa. From the chloroform extract of the stems, A
      new isocucurbitacin (Dendrocyin) with unusual cyclization in the side chain;
      24beta-ethoxy-20-25-epoxy-3alpha,16alpha-dihydroxy-9-methyl-19-norlanost-5(6) ene
      2,11,22-trione has been isolated alongside isocucurbitacin R. Their structural
      configuration were established by usual spectroscopic (1H NMR, 13C NMR and DEPT)
      and two-dimensional NMR techniques (1H-1H Cosy, HMBC and HMQC).

PMID- 15451316
TI  - Terpenoids from Microliabum polymnioides.
AB  - The phytochemical study of M. polymnioides led to the isolation of two
      sesquiterpene lactones namely: 11alphaH-dihydrozaluzanin E and 1beta-hydroxy-4
      oxo-11betaH-4-noreudesman-6,12-olide. Their structures were determined by
      spectroscopic methods. The relative stereochemistry was established by a
      combination of coupling constant analysis, NOESY correlations and molecular
      modeling. Three related known sesquiterpene lactones were also identified, and
      these data were used for chemotaxonomical purposes.

PMID- 15451317
TI  - Allanxanthone B, a polyisoprenylated xanthone from the stem bark of Allanblackia
      monticola Staner L.C.
AB  - In addition to five known compounds including three xanthones, tovophyllin A,
      rubraxanthone and garciniafuran, one pentacyclic triterpene, lupeol and one
      phytosterol, stigmasterol, a polyisoprenylated xanthone named allanxanthone B was
      isolated from the stem bark of Allanblackia monticola. The structure of the new
      compound was assigned as 2-geranyl-1,3,6-trihydroxy-2',2'
      dimethyl[5',6':7,8]xanthone by means of spectroscopic analysis. The antimicrobial
      activities of some of these compounds against a range of micro-organisms are also
      reported.

PMID- 15451318
TI  - Alkaloidal constituents of Mucuna pruriens seeds.
AB  - The seeds of Mucuna pruriens (L.) DC. after chemical analysis afforded four
      tetrahydroisoquinoline alkaloids which have been isolated for the first time from
      M. pruriens. Out of them, two are new whose structures have been elucidated by
      spectroscopic methods.

PMID- 15451319
TI  - Azaphilone pigments from a yellow mutant of the fungus Monascus kaoliang.
AB  - Azaphilone pigments, monascusones A (1) and B (2), together with two known
      azaphilones, monascin (3) and FK17-P2b2 (4), were isolated from the CH2Cl2
      extract of a yellow mutant of the fungus M. kaoliang grown on rice. Structures of
      the isolated compounds were elucidated by analyses of spectroscopic data.
      Monascusone A (1), the major metabolite of M. kaoliang, showed no antimalarial
      (against Plasmodium falciparum), antitubercular (against Mycobacterium
      tuberculosis H37Ra), and antifungal (toward Candida albicans) activities.
      Compound 1 exhibited no cytotoxicity against BC (breast cancer) and KB (human
      epidermoid carcinoma of cavity) cell lines.

PMID- 15451320
TI  - Diterpenoid glucosides from Salvia greggii.
AB  - The structure of four diterpenoid glucosides, designated as salvigresides A-D (1
      4), isolated from the aerial parts of Salvia greggii, have been confirmed by
      spectroscopic and chemical investigation.

PMID- 15451321
TI  - Bioactivity guided isolation of antifungal compounds from the liverwort Bazzania
      trilobata (L.) S.F. Gray.
AB  - A dichloromethane and a methanol extract of the liverwort Bazzania trilobata
      showed antifungal activity against the phytopathogenic fungi Botrytis cinerea,
      Cladosporium cucumerinum, Phythophthora infestans, Pyricularia oryzae and
      Septoria tritici. Bioautography on thin-layer chromatograms was used to isolate
      six antifungal sesquiterpenes: 5- and 7-hydroxycalamenene, drimenol, drimenal,
      viridiflorol, gymnomitrol and three bisbibenzyls: 6 ',8'-dichloroisoplagiochin C,
      isoplagiochin D and 6'-chloroisoplagiochin D. Furthermore we report the isolation
      of gymnomitr-8(12)-en-4-one and the new coumarin 7,8-dihydroxycoumarin-7-O-beta-D
      glucuronide. Their structures have been elucidated based on extensive NMR
      spectral evidence.

PMID- 15451322
TI  - Phloroglucinol derivatives from Mallotus pallidus.
AB  - From the leaves of Mallotus pallidus were isolated five phloroglucinol
      derivatives, namely pallidusol, dehydropallidusol, pallidol, mallopallidol and
      homomallopallidol. Their structures were determined by means of spectroscopic
      methods of analysis.

PMID- 15451323
TI  - Sulfonated xanthones from Hypericum sampsonii.
AB  - Xanthones, 1,3-dihydroxy-5-methoxyxanthone-4-sulfonate and 1,3-dihydroxy-5-O-beta
      D-glycopyranosylxanthone-4-sulfonate, together with nine known compounds were
      obtained from H. sampsonii. This is the first report of sulfonated xanthonoids.
      Furthermore, compounds 1 and 2 exhibited significant cytotoxicity against the
      P388 cancer cell line.

PMID- 15451324
TI  - Aliphatic acid amides of the fruits of Zanthoxylum piperitum.
AB  - Six aliphatic acid amides (1-6) were isolated from the pericarp of Zanthoxylum
      piperitum fruits. MS and NMR spectroscopic investigation revealed that these
      compounds have a ketone and/or hydroxyl group(s) in the unsaturated aliphatic
      acid moiety of the structure of the amides. Combinations 3-4 and 5-6 are
      stereoisomers in terms of the relative configurations of their two asymmetric
      carbons.

PMID- 15451325
TI  - The tornabeatins, four tetrahydro-2-furanone derivatives from the lichenized
      ascomycete Tornabea scutellifera (With.) J.R. Laundon.
AB  - Tornabeatins A, B, C and D, have been isolated as new natural products from the
      lichenized ascomycete Tornabea scutellifera, and their structures elucidated
      using UV, IR, MS, 1D and 2D NMR spectral data and chemical degradation.

PMID- 15451326
TI  - Triterpenoidal glycosides from Justicia betonica.
AB  - dFrom the aerial portion of Justicia betonica L., four triterpenoidal glycosides
      (justiciosides A-D) were isolated. Their structures were established through
      chemical and NMR spectroscopic analyses as olean-12-ene-1beta,3beta,11alpha,28
      tetraol 28-O-beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranoside, olean-12-ene
      1beta,3beta,11alpha,28-tetraol 28-O-beta-D-glucopyranosyl-(1-->2)-beta-D
      glucopyranosyl-(1-->2)-beta-D-glucopyranoside, 11alpha-methoxy-olean-12-ene
      1beta,3beta,28-triol 28-O-beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranoside,
      11alpha-methoxy-olean-12-ene-1beta,3beta,28-triol 28-O-beta-D-glucopyranosyl-(1-
      >2)-beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranoside, respectively.

PMID- 15451327
TI  - Glycosides from Phlomis lunariifolia.
AB  - An aliphatic alcohol glycoside, lunaroside 1-octen-3-yl [O-beta-apiofuranosyl-(1-
      >6)-O-[beta-glucopyranosyl-(1-->2)]-beta-glucopyranoside, a phenylethanoid
      glycoside, lunariifolioside 2-(3,4-dihydroxyphenyl)ethylO-beta-apiofuranosyl-(1-
      >6)-O-[O-beta-apiofuranosyl-(1-->4)-alpha-rhamnopyranosyl-(1-->3)]-4-O-(E)
      caffeoyl-beta-glucopyranoside and a flavone glycoside, luteolin 7-O-[4-O-acetyl
      alpha-rhamnopyranosyl-(1-->2)]-beta-glucuronopyranoside, were isolated from the
      aerial parts of Phlomis lunariifolia, in addition to 15 known glycosides. Their
      structures were elucidated on the basis of extensive 1D and 2D NMR spectroscopic
      interpretation and chemical degradation.

PMID- 15451328
TI  - Ten priorities for women's health.

PMID- 15451329
TI  - Contraceptive efficacy and safety of DMPA-SC.
AB  - DMPA-SC 104 mg/0.65 mL is a new, low-dose subcutaneous (SC) formulation of Depo
      Provera contraceptive injection (150 mg/mL medroxyprogesterone acetate injectable
      suspension) that provides efficacy, safety and immediacy of onset equivalent to
      Depo-Provera intramuscular (IM) injection. Two large, open-label, Phase 3 studies
      assessed the 1-year contraceptive efficacy, safety and patient satisfaction with
      DMPA-SC administered every 3 months (12-13 weeks). Zero pregnancies were reported
      in both studies, which included a total of 16,023 woman-cycles of exposure to
      DMPA-SC and substantial numbers of overweight or obese women. DMPA-SC was well
      tolerated and adverse events were similar to those reported previously with Depo
      Provera IM. Thus, DMPA-SC offers women a new, highly effective and convenient
      long-acting contraceptive option.

PMID- 15451330
TI  - Effect of mefenamic acid on controlling irregular uterine bleeding in DMPA users.
AB  - The objective of this double-blind, placebo-controlled study was to evaluate the
      effect of mefenamic acid and placebo on controlling irregular uterine bleeding in
      depot-medroxyprogesterone acetate (DMPA) users. A total of 48 DMPA users
      attending the Family Planning Clinic, Chulalongkorn Hospital were studied, all
      had abnormal bleeding. These participants were randomly divided into two groups.
      A total of 23 users received mefenamic acid, 500 mg, twice a day for 5 days, and
      placebos were given to the other 25 in the same manner. Total days of bleeding
      and spotting and percentage of women in whom bleeding was stopped were analyzed
      in the first and the fourth week. Percentage of subjects in whom bleeding was
      stopped during the first week after initial treatment was significantly higher in
      the mefenamic acid group than the placebo group (69.6%, 40.0%; p < 0.05). During
      the follow-up period (4 weeks after initial treatment), the mean of the bleeding
      free interval during 28 days was found to be 16.1 days in the subjects treated
      with mefenamic acid and 12.39 days in the placebo group. However, the difference
      was not statistically significant. From the results of the study, we concluded
      that mefenamic acid was effective in very short-term control of bleeding during
      DMPA use, but not effective long-term.

PMID- 15451331
TI  - Outcomes of extended oral contraceptive regimens with a shortened hormone-free
      interval to manage breakthrough bleeding.
AB  - OBJECTIVE: To evaluate in a clinical practice setting the acceptance,
      continuation and variability of extending the active interval of oral
      contraceptives (OCs) with introduction of a shortened hormone-free interval (HFI)
      to manage breakthrough bleeding. METHODS: A retrospective review was undertaken
      of patients seen by one obstetrician/gynecologist and counseled on extending the
      active interval of OCs with a shortened HFI of 3-4 days to manage bleeding.
      Electronic medical records were searched for the phrase "extending the number of
      active pills" for patients counseled between January 1, 2000, and January 31,
      2003, with follow-up through January 31, 2004. A structured query of each
      patient's initial and follow-up records was performed. RESULTS: The 220 patients
      counseled on the extended regimen were 14-52 years of age (mean 36.4, SD 9.3
      years). At initial counseling before extending, the majority of patients cited
      more than one reason for using OCs in the standard fashion with 59% using OCs for
      noncontraceptive reasons. Reasons for extending the active interval of OCs
      included premenstrual symptoms (45%), dysmenorrhea/pelvic pain (40%), heavy
      withdrawal bleeding (36%), menstrual associated headaches (35%), convenience
      (13%), acne associated with menses (10%) and other (15%). Of the 181 patients
      with follow-up data, 174 (96%) attempted an extended regimen with 121 (67%)
      continuing to do so at last follow-up. Follow-up intervals ranged from 0.3 to 3.8
      years (mean 1.6 years). Using Kaplan-Meier product limit survival analysis, 60%
      of patients continued using extended patterns of OCs for more than 2 years. For
      121 currently extending, the HFI varied from 0 to 7 days with 88% utilizing a 0
      to 4 day HFI. CONCLUSIONS: Sixty percent of patients offered extending the active
      interval and shortening the HFI of OCs initiate and continue this pattern for
      more than 2 years without serious sequelae or pregnancy while individually
      directing both the number of days of continuous pills and the length of the HFI.

PMID- 15451332
TI  - How regular is regular? An analysis of menstrual cycle regularity.
AB  - We performed a retrospective analysis to ascertain how accurately women who
      believe that they have regular menstrual cycles estimate the length of their
      actual cycles. Data were extracted from a chart review of subjects from three
      different studies of barrier contraceptives. Subjects were between 18 and 40
      years of age and reported "regular" prestudy menstrual cycles with a consistent
      cycle length between 21 and 35 days. Participants prospectively recorded their
      menses for the up to 30 weeks. Each subject's estimated cycle length was compared
      to the average of her actual cycle lengths and the range and variability in each
      individual's cycle length was calculated. A total of 786 cycles from 130 women
      who recorded 4 or more cycles were analyzed. The averages of the participants'
      estimated cycle lengths was similar to the prospective averages of their actual
      cycle lengths (29.0 +/- 2.7 days vs. 29.1 +/- 3.5 days, respectively, p = 0.8).
      Forty-six percent of all subjects had a cycle range of 7 days or more, and 20%
      had a cycle range of 14 days or more. The average length of menses was 5.2 +/-
      1.0 days. When evaluating only women with cycle lengths from 21 to 35 days, the
      average length of menses was positively associated with the average actual cycle
      length (p = 0.04). Although the average of a woman's menstrual cycles compares
      favorably to her impression of her cycle length, the variability in menstrual
      cycle lengths is significant. This variation may have clinical impact on
      contraceptive practice, contraceptive research studies and pregnancy-related
      care.

PMID- 15451333
TI  - Short-term variations in bone remodeling markers of an oral contraception
      formulation containing 3 mg of drospirenone plus 30 microg of ethinyl estradiol:
      observational study in young postadolescent women.
AB  - The clinical study of treated subjects and nontreated controls was made in
      healthy eumenorrheic young postadolescent women volunteers in the Department of
      Obstetrics and Gynaecology at Cagliari University, to investigate whether an oral
      contraceptive (OC) containing drospirenone (3 mg) plus ethinyl estradiol (30
      microg) (DRSP+EE) can affect bone metabolism. Control group (n = 26) and OC group
      (n = 28) women did not differ in age, body mass index, waist-to-hip ratio and
      main outcome measures [urinary levels of deoxypyridinoline and pyridinoline,
      serum levels of osteocalcin, bone specific alkaline phosphatase (bSAP), total
      testosterone (total-T), sex hormone-binding globulin (SHBG), progesterone and
      bone mineral density (BMD) at the heel]. The control group was studied at the
      luteal phase (LP) during both the first and the sixth menstrual cycle; the OC
      group was studied during the first cycle at the LP, and on days 16-18 of the
      sixth cycle of DRSP+EE treatment. At the sixth cycle, in the control group, the
      main outcome measures did not change compared to baseline. In the OC group,
      deoxypyridinoline, pyridinoline, osteocalcin, bSAP, total-T and progesterone
      levels were reduced, whereas SHBG levels were increased. The BMD was unchanged
      compared to baseline. The results suggest that 6-month DRSP+EE treatment
      decreases bone turnover.

PMID- 15451334
TI  - Concerns about contraceptive side effects among young Latinas: a focus-group
      approach.
AB  - To identify perceptions and attitudes about contraceptive side effects in young,
      low-income Latina adolescents through focus-group conversations. We conducted
      seven focus-group discussions with Latino females in an outpatient clinic and
      community setting. Qualitative methodology was used to analyze data. Participants
      were recruited from the outpatient gynecology clinic at the University of
      Illinois at Chicago, and from the Easter Seals Day Care Center. Women were
      recruited if they were Latino and between the ages of 18 and 26 years (N = 40).
      Participants cited both perceptions of side effects as well as personal
      experience with side effects as reasons for not using or discontinuing the use of
      contraception. Women also demonstrated incorrect knowledge about contraception,
      and tended to value anecdotal information over information from health
      professionals. These factors led to reliance on less-effective methods of
      contraception, placing participants at risk for unintended pregnancy. Concern
      about side effects, fear of health consequences and misinformation were
      identified as barriers to effective contraceptive use in young, low-income
      Latinas. Providers caring for this population should address potential concerns
      about side effects of contraception as well as assess patients' understanding in
      light of cultural and language barriers.

PMID- 15451335
TI  - Comparative study between single dose 600 microg and repeated dose of oral
      misoprostol for treatment of incomplete abortion.
AB  - OBJECTIVE: To evaluate and compare the effectiveness and side effects of two
      regimens of oral misoprostol, single dose (600 microg) and repeated dose (1200
      microg), in the treatment of incomplete abortion. METHODS: A prospective
      randomized controlled trial was conducted. One-hundred women who had incomplete
      abortion (gestational age < 20 weeks) and consented to randomization by computer
      generated randomization model prior to treatment. A single oral 600-microg dose
      or repeated oral dose after 4 h (total 1200 microg) was given to the randomized
      women. RESULTS: The overall incidence of complete abortion was 86.9%. This
      incidence was not statistically different between the single-dose and repeated
      dose groups (81.6% vs. 92%, p > 0.05). However, there was a significantly
      decreased incidence of diarrhea (18.4% vs. 40%, p < 0.05) with the use of single
      dose treatment. Overall rate of acceptability and tolerable side effects were
      88.9% and 97.9%, respectively. These rates were similar in both groups (87.8% vs.
      90% and 98% vs. 98%, p > 0.05). CONCLUSIONS: Oral misoprostol may be a practical
      alternative in the management of incomplete abortion. Oral misoprostol is
      acceptable and tolerable to women. Single-dose regimen is as effective as
      repeated-dose regimen, with a reduction in the incidence of diarrhea.

PMID- 15451336
TI  - Ability of the clinician and patient to predict the outcome of mifepristone and
      misoprostol medical abortion.
AB  - We performed this analysis to evaluate the ability of both women and their
      clinicians to predict pregnancy expulsion after using mifepristone and
      misoprostol for medical abortion up to 63 days gestation. Women who participated
      in a multicenter, randomized trial comparing misoprostol 6-8 h vs. 23-25 h after
      mifepristone attended a follow-up visit approximately 7 days after mifepristone
      treatment. Each subject was asked if she felt she had expelled the gestational
      sac. Clinicians also assessed if the sac had been expelled based on the woman's
      history. Vaginal ultrasonography was then performed to assess the uterine cavity.
      Of the 1080 women enrolled in the multicenter study, 931 (86.2%) who attended the
      first follow-up visit by study day 12 and did not have a uterine suction
      aspiration prior to this visit were included in this analysis. Vaginal
      ultrasonography at the first follow-up visit demonstrated expulsion in 915
      [98.3%, 95% confidence interval (CI): 97.2-99.0] women. Overall, sensitivity,
      specificity, and positive and negative predictive values for subjects were 96.5%,
      31.3%, 98.8% and 13.5%, respectively. When both the clinician and patient felt
      that the gestational sac had passed (n = 880 [94.5%, 95% CI: 92.9-95.9]),
      expulsion was confirmed by sonography in 99.1% (95% CI: 98.2-99.6) of cases.
      Women and clinicians are very accurate at determining expulsion of gestational
      sac during medical abortion with mifepristone and misoprostol without
      ultrasonography or a physical examination.

PMID- 15451337
TI  - Determinants of maternal deaths in induced abortion complications in Ivory Coast.
AB  - Persistently high levels of maternal mortality have been reported in Abidjan, the
      capital of Ivory Coast, with a high prevalence of deaths related to complications
      of induced abortion. In order to assess the determinants of maternal deaths in
      induced-abortion complications, this study investigated women admitted to the
      gynecological departments of four reference hospitals throughout Ivory Coast.
      Information concerning abortion events was collected by means of a questionnaire
      during a confidential, face-to-face interview. Medical records were used to
      collect clinical data and final vital status. In our series, 60% of women
      declared that they induced abortion themselves at their home; a large majority
      mentioned "insertion of objects into the vagina" or "ingestion of traditional
      plants" for this purpose. On the other hand, 40% declared that abortion had been
      performed by a health worker, mostly at a health facility and by using surgical
      methods (dilatation and curettage). Less-educated women were more likely to have
      chosen to induce abortion themselves at home, and more-educated women had
      undergone abortion through a health professional. Our findings highlight the role
      of both women and health professionals in responsibility for induced abortion
      complications.

PMID- 15451338
TI  - Effects of mifepristone on vascular endothelial growth factor and thrombospondin
      1 mRNA in Ishikawa cells: implication for the endometrial effects of
      mifepristone.
AB  - Mifepristone has been used for both medical termination of pregnancy and
      emergency contraception. Mifepristone may have both an antiovulatory activity and
      an antiproliferative effect on the endometrium. We have evaluated the effect of
      mifepristone on vascular endothelial growth factor (VEGF) and thrombospondin-1
      (TSP-1) using Ishikawa cells in vitro. Mifepristone, progesterone and 17beta
      estradiol at concentrations of 1.0, 0.1 and 0.01 microM, were added to confluent
      cells and further cultured for additional 24 h. Total RNA was extracted from
      control and treated cells. After reverse transcription, VEGF, TSP-1 and beta
      actin cDNAs were amplified with polymerase chain reaction spiked with 33p-dCTP.
      The relative abundance of VEGF 121 and 165 isoforms and TSP-1 mRNA were measured
      by scintillation spectroscopy. Mifepristone and progesterone did not stimulate
      VEGF mRNA 121 and 165 isoforms, while 17beta-estradiol increased both VEGF
      isoforms. Mifepristone did not stimulate TSP-1 mRNA at any concentration, but
      progesterone increased TSP-1 mRNA, and this effect was inhibited with
      mifepristone. 17beta-Estradiol did not increase TSP-1 expression. We
      hypothesized, based on these data, that the clinical finding of endometrial
      antiproliferative effect and low vaginal bleeding rate observed in women using
      mifepristone may be related to lack of stimulation of these angiogenic factors.

PMID- 15451339
TI  - A combined regimen of gossypol plus methyltestosterone and ethinylestradiol as a
      contraceptive induces germ cell apoptosis and expression of its related genes in
      rats.
AB  - Attempts to develop gossypol and steroidal hormones alone as a male contraceptive
      have been tested for many years; however, both caused undesirable side effects
      that have prevented their acceptance. In this study, we formulated a regimen of
      combined gossypol at a low dose of 12 mg/kg or a high dose of 50 mg/kg plus
      methyltestosterone 20 mg/kg and ethinylestradiol 100 g/kg daily (12 mg G+H and 50
      mg G+H) administered for 6 weeks in adult rats. The possible roles of germ cell
      apoptosis and related genes expression were studied by techniques of TdT-mediated
      dUTP nick end-labeling (TUNEL), agarose gel electrophoresis of low-molecular
      weight DNA, in situ hybridization and reverse transcription-polymerase chain
      reaction detection. Results showed that germ cell apoptosis and related genes
      expression were significantly induced after combined drug administration. The
      apoptosis index increased 3.86- and 9.65-fold in the 12-mg and 50-mg G+H-treated
      groups, respectively, as compared to the control group. DNA ladder formation on
      the agarose gel further validated the findings of TUNEL-stained apoptotic cells.
      The apoptosis-related genes fas mRNA expression levels increased 0.44- and 1.39
      fold, bax mRNA 0.74- and 2.56-fold, caspase-3 mRNA 0.60- and 1.29-fold, and
      caspase-9 mRNA 2.50- and 4.08-fold, respectively, in the 12-mg and 50-mg G+H
      treated groups vs. the control group. These results indicated that our drug
      regimen applied as a contraceptive could induce rat germ cell apoptosis. The
      apoptotic process involved fas system, bax and caspase family genes and the
      apoptotic extent and cell types were gossypol dose-dependent.

PMID- 15451340
TI  - Effect of long-term progestin treatment on endometrial vasculature in normal
      cycling mice.
AB  - The aim of this study was to develop a mouse model to investigate the effects of
      long-term progestin-only exposure on endometrial vascular structure. Normal
      cycling mice received Silastic implants containing either medroxyprogesterone
      acetate (MPA) or levonorgestrel (LNG) and were dissected after 1, 3 or 6 weeks.
      Endometrial vascular density increased significantly within 1 week of MPA (482 +/
      40.2 vessels/mm2) or LNG (440 +/- 26.5 vessels/mm2) treatment compared with
      normal cycling mice (293 +/- 10.5 vessels/mm2). MPA increased stromal cell
      density within 1 week of treatment (13813 +/- 1450 cells/mm2) compared with
      normal cycling mice (8256 +/- 928 cells/mm2). However, although LNG significantly
      increased stromal cell density overall, the increase did not reach significance
      within the individual weeks examined. There was no significant change in the
      ratio of vascular to stromal cell density among treated and normal cycling mice.
      Epithelial cell height significantly decreased within 1 week of LNG (17.6 +/- 1.3
      microm) treatment compared with normal cycling mice (23.5 +/- 1.3 microm);
      epithelial cell height also decreased within 1 week of MPA treatment (16.6 +/-
      2.1 microm), although this did not reach statistical significance. VEGF
      immunostaining increased significantly in luminal epithelium after MPA or LNG
      treatment, and in glandular epithelium after LNG treatment. These observations
      are similar to those reported in human endometrium, suggesting that this mouse
      model may facilitate further investigations into breakthrough bleeding due to
      long-term progestin use.

PMID- 15451341
TI  - Letter to the editor.

PMID- 15451343
TI  - Failing in analysis of the performance of the gynefix 200 intrauterine system.

PMID- 15451345
TI  - Imaging of acute cervical spine injuries: review and outlook.
AB  - Advances in imaging technology have been successfully applied in the emergency
      trauma setting with great benefit providing early, accurate and efficient
      diagnoses. Gaps in the knowledge of imaging acute spinal injury remain, despite a
      vast wealth of useful research and publications on the role of CT and MRI. This
      article reviews in a balanced manner the main questions that still face the
      attending radiologist by embracing the current and evolving concepts to help
      define and provide answers to the following; Imaging techniques -- strengths and
      weaknesses; what are the implications of a missed cervical spine injury?; who
      should be imaged?; how should they be imaged?; spinal immobilisation -- help or
      hazard?; residual open questions; what does all this mean?; and what are the
      implications for the radiologist? Although there are many helpful guidelines, the
      residual gaps in the knowledge base result in incomplete answers to the questions
      posed. The identification of these gaps in knowledge however should act as the
      initiating stimulus for further research. All too often there is a danger that
      the performance and productivity of the imaging modalities is the main research
      focus and not enough attention is given to the two fundamental prerequisites to
      the assessment of any imaging technology -- the clinical selection criteria for
      imaging and the level of expertise of the appropriate clinician interpreting the
      images.

PMID- 15451346
TI  - Vertebral osteomyelitis without disc involvement.
AB  - Vertebral osteomyelitis is most commonly due to pyogenic or granulomatous
      infection and typically results in the combined involvement of the intervertebral
      disc and adjacent vertebral bodies. Non-infective causes include the related
      conditions of chronic recurrent multifocal osteomyelitis (CRMO) and SAPHO
      (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome. Occasionally,
      these conditions may present purely within the vertebral body, resulting in
      various combinations of vertebral marrow oedema and sclerosis, destructive
      lesions of the vertebral body and pathological vertebral collapse, thus mimicking
      neoplastic disease. This review illustrates the imaging features of vertebral
      osteomyelitis without disc involvement, with emphasis on magnetic resonance
      imaging (MRI) findings.

PMID- 15451347
TI  - Breast.

PMID- 15451348
TI  - Breast imaging findings in women with BRCA1- and BRCA2-associated breast
      carcinoma.
AB  - AIM: To document the breast imaging findings of women with BRCA1 and BRCA2
      associated breast carcinoma. MATERIALS AND METHODS: Family history clinic records
      identified 18 BRCA1 and 10 BRCA2 cases who collectively were diagnosed with 27
      invasive breast carcinomas and four ductal carcinoma in situ (DCIS) lesions. All
      underwent pre-operative imaging (29 mammogram and 22 ultrasound examinations).
      All invasive BRCA-associated breast carcinoma cases were compared with age
      matched cases of sporadic breast carcinoma. RESULTS: Within the BRCA cases the
      age range was 26-62 years, mean 36 years. Two mammograms were normal and 27 (93%)
      abnormal. The most common mammographic features were defined mass (63%) and
      microcalcifications (37%). Thirty-four percent of women had a dense mammographic
      pattern, 59% mixed and 7% fatty. Ultrasound was performed in 22 patients and in
      21 (95%) indicated a mass. This was classified as benign in 24%, indeterminate in
      29% and malignant in 48%. Mammograms of BRCA1-associated carcinomas more
      frequently showed a defined mass compared with BRCA2-associated carcinomas, 72
      versus 36% (73% control group) whilst mammograms of BRCA2-associated carcinomas
      more frequently showed microcalcification, 73 versus 12% (8% control group; p <
      0.001). Thirty-six percent of the BRCA2-associated carcinomas were pure DCIS
      while none of the BRCA1 associated carcinomas were pure DCIS (p = 0.004). Of
      those patients undergoing regular mammographic screening, 100% of BRCA2
      associated carcinomas were detected compared with 75% of BRCA1-associated
      carcinomas. CONCLUSION: These data suggest that the imaging findings of BRCA1 and
      BRCA2-associated carcinomas differ from each other and from age-matched cases of
      sporadic breast carcinoma.

PMID- 15451349
TI  - Imprint cytology from ultrasound-guided core biopsies: accurate and immediate
      diagnosis in a one-stop breast clinic.
AB  - AIM: To investigate whether imprint cytology from ultrasound-guided core biopsy
      specimens was adequate for the National Health Service Breast Screening Programme
      (NHSBSP) guidelines. METHODS: We prospectively audited imprint cytology from
      ultrasound-guided core biopsy specimens. The performance indicators for imprint
      cytology specimens from 111 consecutive ultrasound-guided core biopsy were
      compared with standards set by the NHSBSP for fine-needle aspiration cytology
      (FNAC). RESULTS: Imprint cytology fulfilled the "preferred" targets for absolute
      and complete sensitivity, specificity, positive predictive value, false-positive
      and false-negative rates, inadequate rate and inadequate rate from cancers. It
      also satisfied the minimum target for suspicious rate. The complete sensitivity
      was 97%, full specificity 78%, with 100% positive predictive value for C5
      cytology and an inadequate rate from cancers of 1.5%. CONCLUSION: Imprint
      cytology from ultrasound-guided core biopsy allows same-day diagnosis and the
      collection of data regarding the grade of the carcinoma for treatment decisions
      from a single needle test.

PMID- 15451350
TI  - Ultrasound assessment of carpal tunnel syndrome.

PMID- 15451351
TI  - The role of ultrasonographic measurements of the median nerve in the diagnosis of
      carpal tunnel syndrome.
AB  - AIM: The aim of study was to assess the usefulness of ultrasonographic
      measurements of the median nerve in the diagnosis of carpal tunnel syndrome.
      MATERIALS AND METHODS: Eighty-six patients with carpal tunnel syndrome confirmed
      by electromyography and 45 asymptomatic controls were included in the study and
      underwent high-resolution ultrasonography of the wrists. The cross-sectional area
      and flattening ratio at the level of the pisiform bone of the proximal carpal
      tunnel were measured. Data from the patient group and control group were compared
      to determine the statistical significance. The accuracy of the ultrasonographic
      diagnostic criteria for carpal tunnel syndrome was evaluated using receiver
      operating characteristic (ROC) analysis. RESULTS: One hundred and forty-eight
      wrists of 86 patients with carpal tunnel syndrome and 76 wrists of 45 control
      patients were examined. All measurements showed significant differences between
      patients and controls. Increased cross-sectional area of the median nerve was the
      most predictive measurement of carpal tunnel syndrome. Using the ROC curve, a cut
      off value of >10.5 mm2 at the level of pisiform bone provided a diagnostic
      sensitivity of 89% and specificity of 94.7% CONCLUSION: The ultrasonographic
      measurement of the median nerve cross-sectional area is a sensitive, specific and
      useful non-invasive method for the diagnosis of carpal tunnel syndrome.

PMID- 15451352
TI  - Ultrasonographic assessment of mild and moderate idiopathic carpal tunnel
      syndrome.
AB  - AIM: To investigate the diagnostic value of ultrasonography in mild and moderate
      idiopathic carpal tunnel syndrome (CTS). MATERIALS AND METHODS: Cross-sectional
      areas (CSA), flattening ratios at three different levels, swelling ratio, and
      palmar displacement were analysed in 26 patients (14 with bilateral and 12 with
      unilateral disease, 40 wrists in total) for the presence and the severity of CTS.
      Twenty had normal nerve conduction studies (NCS) defined as "mild", and 20 of
      them had abnormal NCS defined as "moderate". The control group consisted of 20
      healthy participants. RESULTS: All parameters were significantly different
      between patient and control groups. Palmar displacement, swelling ratio, CSA at
      all levels and distal flattening ratio had the highest significance (p < 0.0001).
      The criterion with the highest sensitivity was the swelling ratio > or = 1.3
      (72.5%), followed by the middle CSA > 9 mm2 and the palmar displacement > 2.5 mm.
      All of these criteria had a higher sensitivity in diagnosing moderate cases (85
      100%) than diagnosing mild cases (30-55%). There was a significant difference
      between normal and mild CTS groups regarding palmar displacement, distal
      flattening ratio, middle CSA and swelling ratio (p < 0.0001 for all) and between
      normal and moderate groups regarding all parameters (p < 0.01 - 0.0001) When
      combined middle CSA, palmar displacement and swelling ratio had an overall
      discriminatory accuracy of 83.8%. CONCLUSION: Additional diagnostic confirmation
      can be provided by ultrasonography and may be preferred as the initial step
      instead of electrophysiological studies. Detection of at least two of the three
      criteria (median nerve CSA > 9 mm2 at pisiform level, swelling ratio > or = 1.3,
      and palmar displacement > 2.5 mm) may be helpful for the verification of the
      diagnosis.

PMID- 15451354
TI  - X-ray dose training: are we exposed to enough?
AB  - AIM: To study knowledge of radiation exposure among doctors of various grades and
      specialties in a large district general hospital. METHODS: A multiple-choice
      format questionnaire with a total of 11 questions was distributed amongst doctors
      at Derriford Hospital, Plymouth, UK. Doctors of various grades and specialties
      completed 240 questionnaires which tested knowledge of terrestrial and medical
      radiation exposure. RESULTS: With a pass mark of only 45% and a generous marking
      scheme, only 66 (27.5%) doctors passed. Only 15.4-25.8% of doctors knew the doses
      relative to a chest radiograph of various more complex procedures involving
      ionizing radiation and only 12.5% of doctors were aware of the one in 2000 risk
      of induction of fatal carcinoma from CT of the abdomen. Only 56.7% of
      practitioners who, under Ionizing Radiation (Medical Exposures) Regulations 2000,
      have responsibility for justifying procedures, passed the test. The proportion of
      practitioners correctly identifying the relative dose of a test to a chest
      radiograph varied from 30 to 56.7%, depending on the exam type. Only 20% in this
      group were aware of the risk of inducing a fatal cancer from a CT of the abdomen.
      CONCLUSION: The study demonstrated an urgent need to improve knowledge of
      radiation exposure amongst doctors in clinical practice.

PMID- 15451355
TI  - The value of performing head CT in screening for cerebral metastases in patients
      with potentially resectable non-small cell lung cancer: experience from a UK
      cardiothoracic centre.
AB  - AIM: To evaluate the whether screening for cerebral metastases in neurologically
      intact patients with potentially resectable non-small cell lung cancer patients
      is both worthwhile and cost-effective. METHODS: We prospectively performed
      computed tomography (CT) of the head in 105 consecutive patients with potentially
      resectable lung cancer over an 18-month period. None of these patients had
      neurological symptoms or signs. RESULTS: Five patients (4.8%) with cerebral
      metastases were identified using CT. At our institution the financial saving of
      avoiding five thoracotomies was pound sterling 45,000, whilst the cost of
      performing 105 head CTs was pound sterling 16,000. This represented a substantial
      saving for the healthcare provider and preserved the quality of life in five
      patients. CONCLUSIONS: We conclude that screening for cerebral metastases in
      neurologically intact patients with potentially resectable non small cell lung
      cancer patients is both worthwhile and cost effective.

PMID- 15451356
TI  - Multidetector-row CT duodenography in familial adenomatous polyposis: a pilot
      study.
AB  - AIM: To investigate the feasibility of using multidetector-row computed
      tomography (CT) duodenography to stage duodenal polyposis in patients with
      familial adenomatous polyposis. MATERIALS AND METHODS: Six patients underwent
      multidetector-row CT duodenography before upper gastrointestinal endoscopy. A
      single-blinded radiologist used a surface shaded three-dimensional endoluminal
      fly though and two-dimensional axial and multiplanar reformats to assign a score
      for maximum polyp size and number based on the Spigelman classification.
      Comparison was made with the corresponding Spigelman scores obtained from
      subsequent endoscopy. RESULTS: CT duodenography was technically successful in
      five of six patients. The CT derived Spigelman score based on maximum polyp size
      was accurate in all five patients. The CT derived Spigelman score based on polyp
      number was accurate in only two cases: Polyp number was overestimated in one
      patient and underestimated in a further two. In retrospect, fine carpeting of
      tiny duodenal polyps was poorly visualized with CT. CONCLUSIONS: CT duodenography
      is technically feasible and accurately predicts maximum polyp size but CT
      estimates of polyp number are relatively inaccurate. CT duodenography potentially
      has a useful role for duodenal surveillance in those patients intolerant of
      conventional endoscopy.

PMID- 15451357
TI  - Correlation of power Doppler with microvessel density in assessing prostate
      needle biopsy.
AB  - AIM: To correlate hypervascular power Doppler ultrasonography with the
      histological evaluation of microvasculature in the prostate using trans-rectal
      ultrasound (TRUS)-guided needle biopsy. MATERIALS AND METHODS: Ninety-six
      patients with a lower urinary tract symptoms (LUTS) and prostate specific antigen
      (PSA) value more than 4 ng/ml were evaluated using power Doppler ultrasonography
      before biopsy. The vascularity of the peripheral zone was graded on a scale of
      PZ0 to PZ2. Core needle biopsies were immunostained with CD31(DAKO) and counting
      was performed manually on separate high power fields (HPF; x 400) in areas
      containing the highest number of vessels. RESULTS: There was a significant
      correlation between the grading system used for power Doppler and the microvessel
      density (MVD; PZ0 28.61 +/- 8.97,PZ1 36.00 +/- 12.11 & PZ2 64.008 +/- 15.86; p <
      0.001). There was also a significant difference in MVD between benign, malignant
      and tissue cores with atypia and prostatic intra-epithelial neoplasia (PIN; p <
      0.001 and p < 0.018 respectively). There was a significant correlation between
      malignant tissue having a higher Gleason score and increased MVD (p < 0.001)
      Furthermore, cancer biopsies having a high flow PZ2 are nearly twice as likely
      (63.2%) to have a Gleason score of 7 or more when compared those having a Gleason
      score of less than 7 (36.8%). CONCLUSION: The grading system of assessing the
      power Doppler flow signals appears to be of value as an indicator of MVD. It also
      correlates with a higher Gleason score and this may reflect the clinical outcome
      in prostate cancer. It deserves further study and evaluation as a prognostic
      indicator.

PMID- 15451358
TI  - Technical report: per-oral image-guided insertion of a jejunostomy feeding tube.

PMID- 15451359
TI  - Case report: endovascular parent artery occlusion in a fusiform aneurysm of
      posterior cerebral artery.

PMID- 15451360
TI  - Possible reasons for study results.

PMID- 15451362
TI  - HSV vector-delivery of GDNF in a rat model of PD: partial efficacy obscured by
      vector toxicity.
AB  - Herpes simplex virus (HSV)-derived vectors have been suggested for potential use
      in gene therapy for Parkinson's disease (PD). HSV naturally infects adult
      neuronal cells and possesses a large genome for the insertion of transgenes. In
      the present study, we have used two different HSV constructs to deliver glial
      cell line-derived neurotrophic factor (GDNF) to the striatum, and to assess the
      neuroprotective effects of the GDNF product in an intrastriatal 6-hydroxydopamine
      lesion model. One construct is blocked for IE gene expression whereas the other
      is deleted in the thymidine kinase gene. Both constructs induced a significant
      protection of the dopaminergic neurons in the substantia nigra from the lesions,
      whereas only one induced a transient behavioural recovery in amphetamine-induced
      rotation. Unexpectedly, the more deleted virus caused the greater toxicity. This
      was found to be due to the way the vector was purified. The issue of toxicity,
      which might account for the variable functional effects, needs resolving prior to
      therapeutic application of these vectors.

PMID- 15451363
TI  - Creatine protects against 3-nitropropionic acid-induced cell death in murine
      corticostriatal slice cultures.
AB  - In murine corticostriatal slice cultures, we studied the protective effects of
      the bioenergetic compound creatine on neuronal cell death induced by the
      mitochondrial toxin 3-nitropropionic acid (3-NP). 3-NP caused a dose-dependent
      neuronal degeneration accompanied by an increased lactate dehydrogenase (LDH)
      activity in the cell culture medium. An increased ratio of lactate to pyruvate
      concentration in the medium suggested that metabolic activity shifted to
      anaerobic energy metabolism. These effects were predominantly observed in the 24
      h recovery period after 3-NP exposure. Creatine protected against 3-NP
      neurotoxicity: LDH activity was reduced and aerobic respiration of pyruvate was
      stimulated, which resulted in lower lactate levels and less cell death. In both
      striatum and cortex, apoptosis in 3-NP-exposed slices was demonstrated by
      increased activation of the pro-apoptotic protein caspase-3 and by numerous cells
      exhibiting DNA fragmentation detected by the terminal transferase-mediated
      biotinylated-UTP nick end-labeling (TUNEL) technique. Creatine administration to
      the 3-NP-exposed corticostriatal slices resulted in a reduced number of TUNEL
      positive cells in the recovery period. However, in the striatum, an unexpected
      increase of both TUNEL-positive cells and caspase-3-immunostained cells was
      observed in the exposure phase in the presence of creatine. In the recovery
      phase, caspase-3-immunostaining decreased to basal levels in both striatum and
      cortex. These findings suggest that 3-NP-induced neuronal degeneration in
      corticostriatal slices results from apoptosis that in the cortex can be prevented
      by creatine, while in the more vulnerable striatal cells it may lead to an
      accelerated and increased execution of apoptotic cell death, preventing further
      necrosis-related damage in this region.

PMID- 15451364
TI  - Colocalization of phosphorylated CREB with calcium/calmodulin-dependent protein
      kinase IV in hippocampal neurons induced by ohmfentanyl stereoisomers.
AB  - The transcription factor cAMP response element-binding protein (CREB) plays an
      important role in opioids dependence. To better understand the role of CREB in
      opioids dependence and underlying signal pathways, we compared the effects of
      three ohmfentanyl stereoisomers ((-)-cis-(3R,4S,2'R) OMF (F9202), (+)-cis
      (3R,4S,2'S) OMF (F9204), (-)-cis-(3S,4S,2'R) OMF (F9203)) and morphine on CREB
      phosphorylation and the expression of Ca2+/calmodulin-dependent protein kinase IV
      (CaMKIV) in hippocampus derived from mice which displayed conditioned place
      preference (CPP) behavior by Western blot, and immunohistochemistry analyses.
      Moreover, we studied the effects of OMF and morphine on CREB phosphorylation and
      colocalization of phosphorylated CREB (P-CREB) with CaMKIV in cultured rat
      hippocampal neurons by Western blot, and confocal fluorescence microscopy
      analyses. The results showed that F9202, F9204 or morphine, which could induce
      CPP, enhanced CREB phosphorylation and the expression of CaMKIV in hippocampus
      from CPP mice without affecting total CREB protein level. The CREB
      phosphorylation of cultured hippocampal neurons was also enhanced and reached its
      peak level at 30 min upon exposure to F9202 (100 nM), F9204 (100 nM) or morphine
      (1 microM), while the total CREB protein level was not altered. KN-62 (10
      microM), an inhibitor of CaM kinases, prevented CREB phosphorylation induced by
      morphine, F9202, and F9204 without change of total CREB level. The results of
      confocal fluorescence microscopy further demonstrated that the activated CREB (P
      CREB) was colocalized with CaMKIV in nucleus. F9203, which could not induce CPP,
      failed to increase the CREB phosphorylation and the colocalization of P-CREB with
      CaMKIV both in hippocampus from CPP mice and in cultured hippocampal neurons.
      This is the first evidence to suggest that the increased CREB phosphorylation via
      CaMKIV signal pathway in hippocampus is relevant to opioids psychological
      dependence.

PMID- 15451365
TI  - New synthetic peptides can enhance gene expression of key antioxidant defense
      enzymes in vitro and in vivo.
AB  - Neurodegenerative, cardiovascular, and age-related disorders have been attributed
      to the cellular damage caused by elevated production of reactive oxygen species
      (ROS) and free radicals (FRs). These cannot be adequately defended by existing
      levels of key antioxidant enzymes. Two peptides, 8 and 14 amino acids long, were
      synthesized and found to up-regulate, at nanomolar concentrations, superoxide
      dismutase (SOD) and catalase (CAT) m-RNAs (9- to 12-fold) within 3 h, and then
      elevate by 5- to 10-fold the protein levels of SOD, CAT, and glutathione
      peroxidase (GPX) in rat primary cortical cultures. Kinetic studies showed that
      the peptide up-regulation of all three enzymes appears to be a coordinated
      process which occurs in vitro and in vivo. We also found that ischemia alone,
      without added drugs, can lead to enhanced gene expression of SOD, CAT, and GPX.
      This suggests that the CNS can initiate its own "defense" against ROS and FR.
      Thus, our peptides may activate such systems, as well as AP-1 transcription
      factor, reported in earlier findings to lead to "repair" (growth) of injured
      cells.

PMID- 15451366
TI  - Anxiolytic effects of kindling role of anatomical location of the kindling
      electrode in response to kindling of the right basolateral amygdala.
AB  - Study of effects of kindling on affect has been complicated by the fact that
      anxiogenic, anxiolytic or no effects may be observed following kindling of the
      amygdala. Factors affecting behavioral outcome include strain of rat, hemisphere
      kindled, amygdala nucleus kindled and location of the kindling electrodes within
      particular AP planes of a given nucleus. Previous work has suggested that
      kindling of the right basolateral amygdala (BLA) is predominantly anxiogenic.
      This conclusion was based on kindling of anterior or posterior parts of the BLA.
      The present study sought to clarify this conclusion by examining behavioral
      effects of right BLA kindling in a mid-range of AP planes not yet studied. A
      variety of measures of rodent anxiety-like behavior were examined, including
      behavior in the hole board, elevated plus maze, light/dark box, social
      interaction test and unconditioned acoustic startle. Anhedonic effects of
      kindling were assessed by a sucrose preference test with controls for fluid
      consumption and taste sensitivities. All effects were assessed shortly after
      kindling (1-2 days) and at a longer time interval (7-8 days). Kindling to four
      stage 5 seizures in the mid-right BLA altered behavior at all time points after
      kindling in all tests except the hole board and light/dark box tests. The effect
      of kindling was anxiolytic like in the plus maze, social interaction and startle
      tests. Kindling in mid-BLA also increased sucrose consumption. Effects on sucrose
      consumption are consistent with previous studies showing no depressive-like
      effects of amygdala kindling in rodents. It is hypothesized that the focal nature
      of the behavioral consequences of amygdala kindling are best understood in the
      context of the circuitry in which the cells stimulated are imbedded and the
      impact of kindling on functioning of those circuits.

PMID- 15451367
TI  - Sensitive indicators of injury reveal hippocampal damage in C57BL/6J mice treated
      with kainic acid in the absence of tonic-clonic seizures.
AB  - Sensitive indices of neural injury were used to evaluate the time course of
      kainic acid (KA)-induced hippocampal damage in adult C57BL/6J mice (4 months), a
      strain previously reported to be resistant to kainate-induced neurotoxicity. Mice
      were injected systemically with saline or kainate, scored for seizure severity
      (Racine scale), and allowed to survive 12 h, one, three, or seven days following
      which they were evaluated for neuropathological changes using histological or
      biochemical endpoints. Most kainate-treated mice exhibited limited seizure
      activity (stage 1); however, cupric-silver and Fluoro-Jade B stains revealed
      significant damage by 12 h post-treatment. Immunohistochemistry and immunoassay
      of glial fibrillary acidic protein and lectin staining revealed a strong
      treatment-induced reactive gliosis and microglial activation. Immunostaining for
      immunoglobulin G revealed a kainate-induced breach in the blood-brain barrier.
      Nissl and hematoxylin stains provided little information regarding neuronal
      damage, but revealed the identity of non-resident cells which infiltrated the
      pyramidal layer. Our data suggest sensitive indicators of neural injury evaluated
      over a time course, both proximal and distal to treatment, are necessary to
      reveal the full extent of neuropathological changes which may be underestimated
      by traditional histological stains. The battery of neuropathological indices
      reported here reveals the C57BL/6J mouse is sensitive to excitotoxic neural
      damage caused by kainic acid, in the absence of tonic-clonic seizures.

PMID- 15451368
TI  - Brain activation during vaginocervical self-stimulation and orgasm in women with
      complete spinal cord injury: fMRI evidence of mediation by the vagus nerves.
AB  - Women diagnosed with complete spinal cord injury (SCI) at T10 or above report
      vaginal-cervical perceptual awareness. To test whether the Vagus nerves, which
      bypass the spinal cord, provide the afferent pathway for this response, we
      hypothesized that the Nucleus Tractus Solitarii (NTS) region of the medulla
      oblongata, to which the Vagus nerves project, is activated by vaginal-cervical
      self-stimulation (CSS) in such women, as visualized by functional magnetic
      resonance imaging (fMRI). Regional blood oxygen level-dependent (BOLD) signal
      intensity was imaged during CSS and other motor and sensory procedures, using
      statistical parametric mapping (SPM) analysis with head motion artifact
      correction. Physiatric examination and MRI established the location and extent of
      spinal cord injury. In order to demarcate the NTS, a gustatory stimulus and hand
      movement were used to activate the superior region of the NTS and the Nucleus
      Cuneatus adjacent to the inferior region of the NTS, respectively. Each of four
      women with interruption, or "complete" injury, of the spinal cord (ASIA
      criteria), and one woman with significant, but "incomplete" SCI, all at or above
      T10, showed activation of the inferior region of the NTS during CSS. Each woman
      showed analgesia, measured at the fingers, during CSS, confirming previous
      findings. Three women experienced orgasm during the CSS. The brain regions that
      showed activation during the orgasms included hypothalamic paraventricular
      nucleus, medial amygdala, anterior cingulate, frontal, parietal, and insular
      cortices, and cerebellum. We conclude that the Vagus nerves provide a spinal cord
      bypass pathway for vaginal-cervical sensibility in women with complete spinal
      cord injury above the level of entry into spinal cord of the known genitospinal
      nerves.

PMID- 15451369
TI  - Mild cardiopulmonary arrest promotes synaptic dysfunction in rat hippocampus.
AB  - Cardiac arrest (CA) patients exhibit learning and memory disabilities. These
      deficits suggest that synaptic dysfunction may underlie such disabilities. The
      hypothesis of the present study was that synaptic dysfunction occurs following CA
      and that this precedes cell death. To test this hypothesis, we used
      histopathological and electrophysiological markers in the hippocampus of rats
      subjected to CA. Evoked potentials (EP) were determined in the CA1 region of
      hippocampal slices harvested from animals subjected to CA or sham-operated rats
      by stimulating the Schaffer collaterals and recording in the CA1 pyramidal
      region. EP amplitudes were significantly attenuated by approximately 60% in
      hippocampal slices harvested from animals subjected to CA. Hippocampal slices
      harvested from sham rats exhibited normal long-term potentiation (LTP). In
      contrast, hippocampal slices harvested 24 h after CA exhibited no LTP response,
      even when no histopathological abnormalities were observed. These data suggest
      that synaptic dysfunction occurs before and without overt histopathology. We
      suggest that the synaptic dysfunction precedes and may be an early marker for
      delayed neuronal cell death in the hippocampus after CA.

PMID- 15451370
TI  - Pattern of sensory innervation of the perineal skin in the female rat.
AB  - Here we describe the nerves innervating the perineal skin together with their
      sensory fields in the adult female rat. Electrophysiological recording showed
      that the lumbosacral and L6-S1 trunks, in part by way of the sacral plexus,
      transmit sensory information from the perineal skin via four nerves: the
      viscerocutaneous branch of the pelvic nerve innervating the skin at the midline
      between the vaginal opening and anus, the sensory branch of the pudendal nerve
      innervating the clitoral sheath, the distal perineal branch of the pudendal nerve
      innervating a broad area of skin adjacent to the vaginal opening and anus, and
      the proximal perineal branch of the sacral plexus innervating a broad area of
      skin adjacent to the clitoris and vaginal opening. The sensory fields of three of
      these nerves overlapped to some degree: the viscerocutaneous branch of the pelvic
      and the distal perineal branch of the pudendal nerves at the midline skin between
      the vaginal opening and the anus, and the distal perineal branch of the pudendal
      nerve and the proximal perineal branch of the sacral plexus at the skin lateral
      to the vaginal opening. Such overlap might provide a safeguard helping to ensure
      that somatosensory input from the perineal region important for triggering
      reproductive and nonreproductive reflexes reaches the CNS.

PMID- 15451371
TI  - The superoxide anion is involved in the induction of long-term potentiation in
      the rat somatosensory cortex in vitro.
AB  - The involvement of the superoxide anion (O2-) in the induction of neocortical
      long-term potentiation (LTP) was examined in rat brain slices containing the
      primary somatosensory cortex. Field potentials evoked by stimulation in cortical
      layer IV were recorded from layer II/III. In control experiments, tetanic high
      frequency stimulation (HFS) resulted in essentially input-specific, NMDA receptor
      dependent LTP (20.2+/-3.0% increase in field potential amplitude). When the
      availability of intracellular O2- was reduced by application of the cell membrane
      permeable O2- scavengers MnTBAP or CP-H (spin trap), HFS-induced LTP was
      attenuated to 12.0+/-1.7% and 8.7+/-3.1% increase, respectively. In contrast, HFS
      induced LTP was not significantly affected by the cell membrane-impermeable O2-
      scavenger superoxide dismutase (SOD). Induction of the generation of O2- by the
      cell membrane-permeable redox-cycling quinone DMNQ resulted in a HFS-independent
      slow-onset LTP (21.8+/-6.0%) in three of eight brain slices. Together, these
      results suggest the contribution of O2- to the induction of LTP in the primary
      somatosensory cortex by an action on intracellular induction mechanisms.

PMID- 15451372
TI  - Spatial learning and exploration of environmental stimuli in 24-month-old female
      APP23 transgenic mice with the Swedish mutation.
AB  - Transgenic mice overexpressing the betaAPP gene with the Swedish mutation under
      the control of the murine thy1 promoter show Alzheimer-like characteristics such
      as Abeta plaques in cerebral cortex and vessel walls. By comparison to age
      matched non-transgenic controls, 2-year-old female APP23 transgenic mice crossed
      more segments in the open-field and had a higher number of fast ambulatory and
      stereotyped movements in a photocell activity chamber. In addition, APP23 mice
      entered more often and spent more time in the open arms of the elevated plus
      maze. The acquisition of place learning in the Morris water maze was impaired in
      APP23 transgenic mice, but not in probe and visible platform subtasks. These
      results indicate that hyperactivity and impaired learning abilities characterize
      this mouse model of Alzheimer's disease and cerebral angiopathy.

PMID- 15451373
TI  - Antinociceptive effect of different types of calcium channel inhibitors and the
      distribution of various calcium channel alpha 1 subunits in the dorsal horn of
      spinal cord in mice.
AB  - To understand better which voltage-dependent calcium channels (VGCCs) are
      involved in nociceptive neurotransmission, we investigated the pharmacological
      properties and distribution of VGCCs in the mouse spinal cord. A behavioral assay
      revealed that intrathecal injections of omega-agatoxin TK, omega-agatoxin IVA,
      omega-conotoxin GVIA, and SNX-482, which block P/Q-, P/Q-, N-, and R-type calcium
      channels, respectively, produced analgesic effects, while an L-type channel
      blocker had no such effect. An electrophysiological study demonstrated the
      presence of various types of VGCCs within dorsal root ganglion (DRG) neurons.
      Immunohistochemistry revealed distinct localization of P/Q-, N-, L-, and R-type
      calcium channel subunits to the dorsal horn of the spinal cord. The results of
      this study revealed the localization and functions of several calcium channels
      that are involved in nociceptive neurotransmission within the dorsal horn of the
      mouse spinal cord.

PMID- 15451374
TI  - The antinociceptive effects of spinal cyclooxygenase inhibitors on uterine
      cervical distension.
AB  - Pain during labor is common and severe, as is menstrual pain, and this pain
      originates from the uterine cervix and is transmitted via the hypogastric nerve
      to the spinal cord. Prostaglandins play an important role in nociceptive
      transmission in the spinal cord. Pharmacologically, targeting a specific
      cyclooxygenase (COX) enzyme isoform has as its goal to effectively treat pain
      while avoiding side effects. Both COX-1 and COX-2 inhibitors have been shown to
      effectively treat a variety of pain conditions in animals and in humans; however,
      their efficacy in treatment of acute visceral pain has not been explored. The
      purpose of this study is to evaluate the pharmacologic effects of specific spinal
      COX inhibitors on uterine cervical distention induced nociception. The results
      indicate that intrathecal (i.t.) administration of the COX-2 inhibitor, SC58238,
      and the nonspecific COX inhibitor, indomethacin, effectively inhibited the
      electromyographic activity induced by UCD. None of the inhibitors altered
      hemodynamic response to uterine cervical distension. The study suggests that
      targeting spinal COX-2 could be useful to treat transient and acute visceral pain
      from the uterine cervix.

PMID- 15451375
TI  - Altered endogenous activation of CREB in the suprachiasmatic nucleus of mice with
      retinal degeneration.
AB  - The effect of cone- and rod-cell loss on the activation of transcription factor
      CREB (by phosphorylation at Ser133) was examined in the pacemaker of mammals, the
      suprachiasmatic nucleus (SCN). For this purpose, brain sections of rd/rd and wild
      type C3H mice were immunolabeled with a polyclonal antibody that recognises p
      CREB, i.e., the activated form of the protein. Both rd/rd and wild-type mice
      maintained in constant darkness showed a circadian variation of p-CREB nuclear
      staining: the number of immunopositive nuclear pixels at the subjective night was
      higher than the one observed at the subjective day. However, some differences
      were detected between both groups: (1) p-CREB immunolabelling in the SCN of rd/rd
      mice was significantly reduced throughout the 24-h cycle; (2) the time in which
      the activation of CREB begins to increase at the subjective night in these mice
      is delayed with regard to wild-type mice. When a light stimulus was given at the
      subjective night p-CREB immunostaining significantly increased in the SCN of both
      rd/rd and wild-type mice when compared to basal levels, while no significant
      effect was found when the stimulus was given at the subjective day. Taken
      together, our results suggest that despite lower levels of p-CREB, indicating
      that something is altered in the SCN of rd/rd mice, the main mechanisms of the
      clock (e.g., circadian oscillation, readjustment by light) are still fully
      functional in these mice. The present study supports the idea that the CREB/CRE
      pathway is a component of the circadian clock molecular mechanism.

PMID- 15451376
TI  - Intrathecal CART (55-102) enhances the spinal analgesic actions of morphine in
      mice.
AB  - Cocaine- and amphetamine-regulated transcript (CART) peptides are found in brain
      and spinal cord areas involved in pain transmission. In the present study, we
      investigated the role of rat CART (55-102) in the modulation of an acute pain
      model after intrathecal administration. The results show that CART (55-102) was
      without effect on the tail-flick test after i.t. injection in mice.
      Interestingly, i.t. administration of CART (55-102) significantly enhanced the
      antinociceptive effect of morphine in the tail-flick test. These results suggest
      that CART (55-102) potentiates the effects of opioids to inhibit the nociceptive
      information transmission.

PMID- 15451377
TI  - Ischemia-induced increase in long-term potentiation is warded off by specific
      calpain inhibitor PD150606.
AB  - In the present study, the effect of specific, membrane-permeable calpain
      inhibitor, PD150606, was analysed on synaptic efficacy in in vitro brain slices
      experiments after ischemic insult of rats in vivo, and on cell viability in a
      glutamate excitotoxicity test in mouse cell culture. Bilateral common carotid
      artery ligation (BCCL) for 24 h markedly increased calpain activity and enhanced
      LTP induction in rat hippocampus, although the CA1 layer significantly shrank.
      The enhancement of LTP could be diminished by short-term application of PD150606
      (40 microM) into the perfusion solution. Intracerebroventricular administration
      of PD150606 (100 microM) parallel with ischemic insult prevented LTP and
      effectively inhibited hippocampal calpain activity. Intracerebroventricularly
      applied PD150606 inhibited the CA1 layer shrinkage after common carotid ligation.
      High level of exogenous glutamate caused marked decrease of cell viability in
      mouse cerebellar granule cell cultures, which could be partly warded off by 20
      microM PD150606. Our data witness that calpain action is intricately involved in
      the regulation of synaptic efficacy.

PMID- 15451378
TI  - Down-regulation of dopamine D1 and D2 receptors in the basal ganglia of PTZ
      kindling model of epilepsy: effects of angiotensin IV.
AB  - The present study examined the effect of pentylenetetrazol (PTZ) induced kindling
      as well as the action of the hexapeptide angiotensin IV (ANG IV) on the dopamine
      (DA) D1 and D2 receptor binding in the basal ganglia of the mouse brain. By using
      quantitative receptor autoradiography, it was found that PTZ kindling led to a
      decrease in DA D2 receptor density (about 20%) in all regions of the neostriatum
      (NS) as well as in the olfactory tubercle (OT), the nucleus accumbens (NA) and
      the globus pallidus, which persisted 24 h and 7 days after the kindling
      procedure. PTZ induced kindling also elicited a decrease in DA D1 receptor
      binding sites (about 10%), which however was, restricted to the rostral NS (rNA)
      and NA. ANG IV (0.2 mg/kg), injected prior to PTZ, not only prevented the
      development of the kindling process but it also reversed the kindling-induced
      down-regulation of both DA receptors to the control levels. Furthermore ANG IV
      induced an area-specific increase of DA D1 receptor density above control levels
      in the dorsal part of rNS. These findings suggest that DA D2 receptors could
      mainly contribute to epileptogenesis in the PTZ kindling model, whereas the role
      of DA D1 receptors is limited to particular regions in the basal ganglia. The
      anticonvulsant effect of ANG IV pretreatment might be influenced by a DA-related
      mechanism and particularly by preventing D2 receptor down-regulation as well as
      by an adaptive area-specific increase in DA D1 receptors.

PMID- 15451379
TI  - Spectral-shape preference of primary auditory cortex neurons in awake cats.
AB  - The study of the influence of spectral envelopes of complex tones on cortical
      neuron discharges is important with respect to understanding the formant
      processing of vowels. That the sharpness of formants can contribute to the vowel
      quality has previously been shown in psychophysical experiments. However, it is
      unknown how this parameter is reflected by cortical neuron discharges, especially
      when a formant falls into different portions of the neuronal frequency receptive
      field (FRF). To show this is the aim of this study focusing on the sustained
      discharging neurons in the low frequency portion of cat primary auditory cortex
      (A1). The stimuli were multi-frequency tones whose spectral envelope was
      sinusoidally modulated with a peak fixed at a neuron's best frequency. The
      modulation depth, defined as damping-amplitude (DA), varied systematically.
      Stimulus bandwidth also varied systematically. Large DA at off-center frequencies
      produces a prominent spectral peak with steep slope, whereas small DA has a less
      well-defined spectral peak with gentle slope. Single frequency and two tone
      stimuli served to delineate the excitatory and inhibitory subfields of FRF. The
      A1 neuron preferred large DA when the sound energy fell into FRF with the
      relatively large inhibitory-subfield, while the same cell preferred small DA when
      it fell into FRF with the relatively small inhibitory-subfield. It is concluded
      that the A1 neuron can estimate steepness of slope of a spectral peak, and that a
      preference for steep slopes stems from a shift of balance toward the spectral
      inhibition, whereas a preference for gentle slopes, toward the spectral
      excitation.

PMID- 15451380
TI  - Enhanced visuomotor associative learning following stimulation of alpha 2A
      adrenoceptors in the ventral prefrontal cortex in monkeys.
AB  - The present study investigated the effect of locally infused guanfacine, an
      alpha2A-adrenergic agonist, into the ventral prefrontal cortex (PFv) on
      visuomotor associative learning. Two monkeys were well trained on a two-problem
      visuomotor associative task: the monkeys performed movement A if presented with a
      circle pattern, or movement B if presented with a triangle pattern. For learning
      of new visuomotor associations, the monkeys were presented with a new set of four
      patterns in each and every daily session, two of which instructed movement A and
      the other two movement B. Bilaterally infused guanfacine (2.5 microg/microl; 3
      microl on each side) improved the monkeys' ability to learn new visuomotor
      associations: trials and errors to learning criterion of 90% correct decreased
      significantly. The monkeys showed an enhanced capability to use win-stay/lose
      shift strategy on 'repeat trials' and change-stay/change-shift strategy on
      'change trials.' The present results indicate that alpha2A-adrenoceptor in the
      PFv is involved in regulating visuomotor associative learning.

PMID- 15451381
TI  - The effect of escitalopram, desipramine, electroconvulsive seizures and lithium
      on brain-derived neurotrophic factor mRNA and protein expression in the rat brain
      and the correlation to 5-HT and 5-HIAA levels.
AB  - The reported increase in brain-derived neurotrophic factor (BDNF) mRNA expression
      after antidepressant treatment is a cornerstone of the BDNF hypothesis of
      antidepressant action. However, if this increase becomes manifest on the BDNF
      protein level is unknown. In the present study we performed parallel measurements
      of BDNF mRNA and protein expression in the frontal cortex and hippocampus of the
      rat after chronic treatment with electroconvulsive seizures (ECS), lithium,
      desipramine or escitalopram. ECS increased BDNF mRNA and protein in the
      hippocampus and BDNF protein in the frontal cortex. Desipramine moderately
      increased BDNF mRNA expression in the dentate gyrus but did not change BDNF
      protein in neither region. Escitalopram did not affect BDNF mRNA expression, but
      decreased BDNF protein in the frontal cortex and the hippocampus. Lithium
      increased BDNF protein levels in the hippocampus and frontal cortex, but overall
      decreased BDNF mRNA expression. Thus, here we report a striking non
      correspondence between changes in BDNF mRNA and protein expression induced by the
      antidepressant treatments and lithium. Further, increased expression of BDNF mRNA
      or protein was not a common action of the treatments. We also investigated if
      treatment-induced modulations of the tissue contents of 5-hydroxytryptamine (5
      HT) and its metabolite, 5-hydroxy-indoleacetic acid (5-HIAA), were related to
      changes in BDNF mRNA or protein expression. No correlation was found. However,
      all treatments increased 5-HT levels in the hippocampus.

PMID- 15451382
TI  - Vimentin-expressing proximal reactive astrocytes correlate with migration rather
      than proliferation following focal brain injury.
AB  - Vimentin-expressing astrocytes in the adult are commonly associated with the
      proximal, most reactive gliotic response ultimately leading to the formation of a
      new glial limitans. It was thought, since vimentin expression and astroglial
      proliferation are most prominent nearest the lesion site, that vimentin may be a
      characteristic of immature newly divided astrocytes. We recently established a
      unique distribution of vimentin-expressing reactive astrocytes at the base of a
      focal cortical ischemic lesion in rats. The purpose of the present study was to
      assess the correlation of proliferation and migration with this unique
      distribution following focal injury. With the use of bromodeoxyuridine (BrdU) and
      immunohistochemistry for astrocytes and microglia/macrophages, proliferation and
      migration of cells was shown to be throughout the ipsilateral hemisphere on day
      one and become progressively more centralized to the lesion by day 3. The
      vimentin-expressing area at the base of the lesion does not exhibit
      distinguishable proliferation rates from non-vimentin-expressing regions
      surrounding the lesion and did not demonstrate obvious double labeling with BrdU+
      cells, although on occasion vimentin expression is closely associated with BrdU.
      However, this region did become a focal point for migration into and around the
      lesion by day 3. Additionally, asymmetrical distribution of vimentin was shown in
      four different injury models with vimentin+ cells always situated between the
      lesion and the corpus callosum. It is concluded that although vimentin-expressing
      cells did not correlate with proliferating cells in these focal injury models,
      perhaps this distinct population of reactive astrocytes serve as a source of
      cytokines or as a physical conduit for migrating cells from distant sites through
      the corpus callosum.

PMID- 15451383
TI  - Distinct rat neurohypophysial nerve terminal populations identified by size,
      electrophysiological properties and neuropeptide content.
AB  - Voltage-gated ion channels are critical to excitation-secretion coupling in nerve
      terminals. We have identified two distinct populations of rat neurohypophysial
      (NHP) terminals distinguished by size, neuropeptide content and
      electrophysiological properties, including resting membrane potential, action
      potential (AP) properties, and K+ current and Na+ current characteristics. In
      large terminals (10-16 microm diameter), resting membrane potential was more
      negative than in small terminals (5-9.9 microm; -61+/-4 mV vs. -55+/-3 mV;
      p<0.01), action potential amplitude was larger (69+/-4 mV vs. 53+/-3 mV; p<0.01),
      peak IK was larger (1460+/-90 pA vs. 1140+/-70 pA; p<0.05) with a more negative
      V1/2 for activation (-3.1 mV vs. -0.6 mV; p<0.05), and Na+ current density was
      greater (approximately 470 pA/pF vs. approximately 300 pA/pF; p<0.01) with more
      negative V1/2 values for activation from -70 or -90 mV holding potentials (-44 mV
      vs. -24 mV; p<0.01). A positive linear correlation between INa amplitude and
      terminal size showed an inflection at a diameter of 9.2 microm. Neuropeptide
      content was generally segregated into a population of small terminals (<10 microm
      diameter) containing predominantly vasopressin and a population of large
      terminals (> or =10 microm diameter) containing predominantly oxytocin (OT); a
      small fraction of terminals in each group contained both peptides. These findings
      suggest that electrophysiological differences between small vasopressin
      containing and large oxytocin-containing neurohypophysial terminals may
      contribute to their observed differential firing and peptide release patterns.

PMID- 15451384
TI  - Characterization of modulatory effects of postsynaptic metabotropic glutamate
      receptors on calcium currents in rat nucleus tractus solitarius.
AB  - It is well known that metabotropic glutamate receptors (mGluRs) have multiple
      actions on neuronal excitability mediated by G-protein-coupled receptors,
      although the exact mechanisms by which these actions occur are not understood.
      This study examines the effects of mGluRs agonists on voltage-dependent Ca2+
      channels (VDCCs) currents (ICa) in the nucleus tractus solitarius (NTS) of rats
      using patch-clamp recording methods. An application of (RS)-3,5
      dihydroxyphenylglycine (DHPG, Group I mGluR agonist) caused both facilitation and
      inhibition of L-type and N/P/Q-types ICa, respectively. Neither (2S, 2'R, 3'R)-2
      (2', 3'-dicarboxycyclopropyl)glycine (DCG, Group II mGluRs agonist) nor L-(+)-2
      amino-4-phosphonobutyric acid (AP-4, Group III mGluRs agonist) nor (RS)-2-chloro
      5-hydroxyphenylglycine (CHPG, mGluR5 agonist) modulated ICa. Intracellular
      dialysis of the Gq/11-protein antibody and Gi-protein antibody attenuated the
      DHPG-induced facilitation and inhibition, respectively. The phospholipase C (PLC)
      inhibitor, as well as inhibition of either the protein kinase C (PKC) or inositol
      1,4,5-trisphosphate (IP3) attenuated the DHPG-induced facilitation of ICa but not
      a DHPG-induced inhibition. Application of a strong depolarizing voltage prepulse
      attenuated the DHPG-induced inhibition of ICa. These results indicate that mGluR1
      facilitates L-type VDCCs via Gq/11-protein involving PKC including IP3 formation.
      On the other hand, mGluR1 inhibits N- and P/Q-types VDCCs via Gi-protein
      betagamma subunits.

PMID- 15451385
TI  - Impaired motor performance and learning in glia maturation factor-knockout mice.
AB  - Glia maturation factor (GMF) is a unique brain protein localized in astrocytes
      and some neuronal populations. Studies with overexpression of GMF using
      adenovirus vector have uncovered its regulatory role in intracellular signal
      transduction and downstream induction of biologically active molecules, including
      the neurotrophins and cytokines. The current paper deals with the behavior of
      mice devoid of GMF protein (knockout). GMF-null mice developed normally without
      gross abnormality. When tested for simple position discrimination using a T-maze
      and for spatial memory using a Morris water maze, the knockout mice performed as
      well as the wild-type, showing no defect in maze learning. However, with beam
      walking, GMF-knockout mice performed poorly and failed to learn. Knockout mice
      were also defective in learning the eyeblink classical conditioning.
      Histologically, the knockout mice showed a loss of neurons in the inferior olive,
      which is a component of the circuitry of eyeblink conditioning, and is also
      essential for motor performance. The structural abnormality in GMF-null mice
      explained their impaired ability for both motor performance and motor learning.

PMID- 15451386
TI  - A selective increase in phosphorylation of cyclic AMP response element-binding
      protein in hippocampal CA1 region of male, but not female, rats following
      contextual fear and passive avoidance conditioning.
AB  - Cyclic AMP response element-binding protein (CREB), a transcription factor on
      which multiple signal transduction pathways converge, has been implicated in long
      term memory. We examined whether the sex difference in the performance of
      contextual fear or passive avoidance conditioning is associated with a change in
      the activation of CREB in the hippocampus, a neural structure important for long
      term memory. The activation of CREB in different subregions within the
      hippocampus in male and female rats was determined immunohistochemically with an
      antibody that specifically recognizes the phosphorylated form of CREB (pCREB).
      With respect to the freezing time in contextual fear conditioning and the step
      through latency in passive avoidance conditioning, male rats exhibited better
      performance than female rats. Phosphorylation of CREB (% pCREB) as revealed by
      the ratio of the pCREB-immunoreactive (pCREB-ir) cell number to the CREB
      immunoreactive cell number was increased in the CA1 region, but not in CA3, CA4,
      or in the dentate gyrus following training for both types of conditioning in
      males. In females, such an increase in % pCREB was not found in any hippocampal
      subregion at any time after conditioning or by increasing the intensity of foot
      shock. Orchidectomy in males did not alter either the performance of contextual
      conditioning or conditioning-induced CREB phosphorylation in CA1. The close
      relationship between behavioral performance and CREB phosphorylation in the CA1
      region suggests that hippocampal CREB is involved in the sex difference in some
      forms of learning and memory.

PMID- 15451387
TI  - Central effect of mu-opioid agonists on antral motility in conscious rats.
AB  - Centrally applied opioids delay gastric emptying and inhibit intestinal transit.
      However, the mechanism of inhibitory effects of central opioids on gastric
      motility still remains unclear. It also remains unclear which opioid receptor
      (mu, delta, and kappa) stimulation affects gastric motility. We studied the
      central effect of opioids on antral motility in conscious rats. A strain gauge
      transducer was implanted on the gastric antrum to record the circular muscle
      contractions. The area under the curve of the antral motility, calculated as a
      motility index, was evaluated before and after the intracerebroventricular (icv)
      injection of various opioid agonists in each rat. [D-Ala2, N-Me-Phe4, Gly5-ol]
      enkephalin (DAMGO, 0.1-10 nmol), a mu-opioid selective agonist, significantly
      inhibited antral motility in a dose-dependent manner (n=4). The motility index
      was significantly decreased to 47.3+/-10.8% (n=4) of controls at 20 min after icv
      injection of DAMGO (1.0 nmol). In contrast, [D-pen2, L-Pen5] enkephalin (DADLE,
      1.0 nmol), a delta-opioid selective agonist, and U50,488 (1.0 nmol), a kappa
      opioid selective agonist, had no significant effects on antral motility.
      Pretreatment with subcutaneous guanethidine (5 mg/kg) and propranolol (1 mg/kg),
      but not phentolamine (1 mg/kg), significantly antagonized the inhibitory effect
      of DAMGO (1.0 nmol). Reduced motility index induced by DAMGO (1.0 nmol) was
      restored from 48.7+/-3.5% to 88.6+/-10.9% (n=5) and 80.4+/-2.2% (n=5) by
      guanethidine and propranolol, respectively. Our findings suggest that central mu
      opioid receptor has major inhibitory effects on antral motility in conscious
      rats. The inhibitory effects of mu-opioid receptors are mediated via sympathetic
      pathways and beta-adrenoceptors.

PMID- 15451388
TI  - Differential brain activation in exclusively homosexual and heterosexual men
      produced by the selective serotonin reuptake inhibitor, fluoxetine.
AB  - A number of studies have shown a relationship between "sexual orientation" and
      size of various brain nuclei. We hypothesized that neurotransmitter differences
      might parallel neuroanatomical differences in the hypothalamus. We administered
      40 mg of fluoxetine as a challenge to the serotonergic systems of exclusively
      homosexual and exclusively heterosexual men and measured cerebral metabolic
      changes with fluorodeoxyglucose positron emission tomography (FDG-PET). The
      metabolic differences we observed might reflect underlying neurochemical
      differences between homosexual and heterosexual men.

PMID- 15451389
TI  - Six decades of GABA.

PMID- 15451390
TI  - SGS742: the first GABA(B) receptor antagonist in clinical trials.
AB  - The GABA(B) receptor antagonist SGS742 (CGP36742) displays pronounced cognition
      enhancing effects in mice, young and old rats and in Rhesus monkeys in active and
      passive avoidance paradigms, in an eight-arm radial maze and a Morris water maze
      and in a social learning task. SGS742 blocks the late inhibitory postsynaptic
      potential and the paired-pulse inhibition of population spikes recorded from CA1
      pyramidal neurons of the hippocampus of rats in vitro and in vivo. SGS742
      significantly enhances the release of glutamate, aspartate, glycine and
      somatostatin in vivo. Chronic administration of SGS742 causes an up-regulation of
      GABA(B) receptors in the frontal cortex of rats. Single doses cause a significant
      enhancement of the mRNA and protein levels of NGF and BDNF in the cortex and
      hippocampus of rats. The observed antidepressant effects of SGS742 in rats may be
      explained by these findings. SGS742 was well tolerated in experimental animals as
      well as in young and elderly human volunteers with an absolute bioavailability in
      humans of 44%. In a Phase II double-blind, placebo-controlled study in 110
      patients with mild cognitive impairment (MCI), oral administration of SGS742 at a
      dose of 600 mg t.i.d. for 8 weeks significantly improved attention, in particular
      choice reaction time and visual information processing as well as working memory
      measured as pattern recognition speed. A second Phase II clinical trial in 280
      Alzheimer's disease patients is underway.

PMID- 15451391
TI  - Effect of antidepressants on GABA(B) receptor function and subunit expression in
      rat hippocampus.
AB  - Laboratory and clinical studies suggest that depression is associated with
      changes in the hippocampus and that this brain region is a major target for
      antidepressant drugs. Given the data suggesting that GABA(B) receptor antagonists
      display antidepressant properties, the present study was undertaken to assess the
      effect of antidepressant administration on GABA(B) receptors in the rat
      hippocampus to determine whether changes in this regional receptor system may
      play a role in the response to these agents. Rats were administered (i.p.) the
      monoamine oxidase inhibitors tranylcypromine (10mg/kg) or phenelzine (10mg/kg),
      the tricyclic antidepressant desipramine (15 mg/kg), or fluoxetine (5mg/kg), a
      selective serotonin re-uptake inhibitor, once daily for seven consecutive days.
      Two hours following the last drug treatment the hippocampal tissue was prepared
      for defining the distribution and quantity of GABA(B) receptor subunits using in
      situ hybridization and for assessing GABA(B) receptor function by quantifying
      baclofen-stimulated [(35)S]-GTPgammaS binding. All of these antidepressants
      selectively increased the expression of the GABA(B(1a)) subunit in hippocampus,
      having no consistent effect on the expression of GABA(B(1b)) or GABA(B(2)).
      Moreover, except for fluoxetine, these treatments increased GABA(B) receptor
      function in this brain region. The results indicate that an enhancement in the
      production of hippocampal GABA(B(1a)) subunits may be a component of the response
      to antidepressants, supporting a possible role for this receptor in the symptoms
      of depression and the treatment of this condition.

PMID- 15451392
TI  - GABA(A) receptor epilepsy mutations.
AB  - Idiopathic generalized epilepsy (IGE) syndromes are diseases that are
      characterized by absence, myoclonic, and/or primary generalized tonic-clonic
      seizures in the absence of structural brain abnormalities. Although it was long
      hypothesized that IGE had a genetic basis, only recently have causative genes
      been identified. Here we review mutations in the GABA(A) receptor alpha1, gamma2,
      and delta subunits that have been associated with different IGE syndromes. These
      mutations affect GABA(A) receptor gating, expression, and/or trafficking of the
      receptor to the cell surface, all pathophysiological mechanisms that result in
      neuronal disinhibition and thus predispose affected patients to seizures.

PMID- 15451393
TI  - The GABA-glutamate connection in schizophrenia: which is the proximate cause?
AB  - Schizophrenia is a chronic, disabling psychiatric disorder that genetic studies
      have shown to be highly heritable. Although the dopamine hypothesis has dominated
      the thinking about the cause of schizophrenia for 40 years, post-mortem and
      genetic studies have provided little support for it. Rather, post-mortem studies
      point to hypofunction of subsets of GABAergic interneurons in the prefrontal
      cortex and the hippocampus. Furthermore, clinical pharmacologic, post-mortem and
      genetic studies have provided compelling evidence of hypofunction of a
      subpopulation of NMDA receptors in schizophrenia. In support of this inference,
      agents that directly or indirectly activate the glycine modulatory site on the
      NMDA receptor (the Glycine B receptor) reduce symptoms in chronic schizophrenia,
      especially negative symptoms and cognitive impairments. Electrophysiologic and
      pharmacologic studies suggest that the vulnerable NMDA receptors in schizophrenia
      may be concentrated on cortico-limbic GABAergic interneurons, thereby linking
      these two neuropathologic features of the disorder.

PMID- 15451394
TI  - A role for GABA mechanisms in the motivational effects of alcohol.
AB  - Low doses of ethanol have been hypothesized to act directly via proteins that
      form ligand-gated receptor channels, such as the gamma-aminobutyric acid (GABA)
      receptor complex, to allosterically alter function, particularly in specific
      brain areas such as those hypothesized to be involved in ethanol reinforcement.
      At the pharmacological level, one can antagonize the effects of ethanol with GABA
      antagonists, particularly its sedative, anxiolytic-like and acute reinforcing
      actions. Brain sites involved in the GABAergic component of ethanol reinforcement
      include the ventral tegmental area, elements of the extended amygdala (including
      the central nucleus of the amygdala), and the globus pallidus. Chronic
      administration of ethanol sufficient to produce dependence and increased ethanol
      intake are associated with increased GABA release in the amygdala and increased
      sensitivity to GABA agonists. A hypothesis is proposed that GABAergic
      interactions with the brain stress neurotransmitter corticotropin-releasing
      factor in specific elements of the extended amygdala may be an important
      component for the motivation for excessive drinking associated with the
      transition from social drinking to addiction.

PMID- 15451395
TI  - Unravelling the unusual signalling properties of the GABA(B) receptor.
AB  - GABA(B) receptors are the cornerstone receptors in the modulation of inhibitory
      signalling in the central nervous system and continue to be targets for the
      amelioration of a number of neuropsychiatric and neurological disorders.
      Unravelling the molecular identity of this receptor has spurred much research
      over the past five or so years and generated a renewed interest and excitement in
      the field. Many questions are being answered and lessons learnt, not only about
      GABA(B) receptor function but also about general mechanisms of G-protein-coupled
      receptor signalling. However, as questions are being answered as many new
      questions are being raised and many GABA(B)-related conundrums continue to remain
      unanswered. In this report, we review some of the most recent work in the area of
      GABA(B) receptor research. In particular, we focus our attentions on the emerging
      mechanisms thought to be important in GABA(B) receptor signalling and the growing
      complex of associated proteins that we consider to be part of the GABA(B)
      receptor "signalosome."

PMID- 15451396
TI  - GABA pharmacology--what prospects for the future?
AB  - Following the recognition of GABA as an inhibitory neurotransmitter, the
      discovery of high affinity GABA uptake, and the characterisation of GABA
      receptors great progress has been made in developing GABA pharmacology.
      Tiagabide, the first marketed GABA uptake inhibitor may be followed by new and
      more selective uptake inhibitors. Knowledge of the molecular pharmacology of GABA
      A receptors, both synaptic and non-synaptic, may lead to improved anti
      anxiety/anticonvulsant agents devoid of the sedative and dependence liabilities
      of earlier compounds and new hypnotics. Gaboxadol (THIP) is an example of a novel
      hypnotic that acts on GABA-A receptors by a non-benzodiazepine mechanism.
      Exploiting neurosteroid interactions with GABAergic mechanisms also holds much
      future promise.

PMID- 15451397
TI  - GABA(B) receptor alterations as indicators of physiological and pharmacological
      function.
AB  - Given the widespread distribution of GABA(B) receptors throughout the central
      nervous system, and within certain peripheral organs, it is likely their
      selective pharmacological manipulation could be of benefit in the treatment of a
      variety of disorders. Studies aimed at defining the clinical potential of GABA(B)
      receptor agonists and antagonists have included gene deletion experiments,
      examination of changes in receptor binding, subunit expression and function in
      diseased tissue, as well as after the chronic administration of drugs. The
      results indicate that a functional GABA(B) receptor requires the combination of
      GABA(B(1)) and GABA(B(2)) subunits, that receptor function does not always
      correlate with subunit expression and receptor binding, and that GABA(B) receptor
      modifications may be associated with the clinical response to antidepressants,
      mood stabilizers, and GABA(B) receptor agonists and antagonists. Moreover,
      changes in GABA(B) binding or expression suggest this receptor may be involved in
      mediating symptoms associated with chronic pain, epilepsy and schizophrenia.
      This, together with results from other types of studies, indicates the potential
      therapeutic value of developing drugs capable of selectively activating,
      inhibiting, or modulating GABA(B) receptor function.

PMID- 15451398
TI  - How does a little acronym become a big transmitter?
AB  - After an overview of the early, chequered history of the discovery of GABA and
      its gradual acceptance as inhibitory synaptic transmitter in the brain, the
      article lists and discusses some of the more unexpected later developments in
      studies of GABA, especially its role as excitatory transmitter in the immature
      brain.

PMID- 15451399
TI  - GABA transporters as drug targets for modulation of GABAergic activity.
AB  - The identification and subsequent development of the GABA transport inhibitor
      tiagabine has confirmed the important role that GABA transporters play in the
      control of CNS excitability. Tiagabine was later demonstrated to be a selective
      inhibitor of the GABA transporter GAT1. Although selective for GAT1, tiagabine
      lacks cell type selectivity and is an equipotent inhibitor of neuronal and glial
      GAT1. To date, four GABA transporters have been cloned, i.e., GAT1-4. The finding
      that some of these display differential cellular and regional expression patterns
      suggests that drugs targeting GABA transporters other than GAT1 might offer some
      therapeutic advantage over GAT1 selective inhibitors. Furthermore, it is
      particularly interesting that several recently defined GABA transport inhibitors
      have been demonstrated to display a preferential selectivity for the astrocytic
      GAT1 transporter. That cellular heterogeneity of GAT1 plays a role in the control
      of CNS function is confirmed by the demonstration that inhibition of astrocytic
      GABA uptake is highly correlated to anticonvulsant activity. At the present time,
      a functional role for the other GABA transporters is less well defined. However,
      recent findings have suggested a role for the mouse GAT2 (homologous to the human
      betaine transporter) in the control of seizure activity. In these studies, the
      non-selective GAT1 and mouse GAT2 transport inhibitor EF1502 (N-[4,4-bis(3-methyl
      2-thienyl)-3-butenyl]-3-hydroxy-4-(methylamino)-4,5,6,7
      tetrahydrobenzo[d]isoxazol-3-ol) was found to exert a synergistic anticonvulsant
      action when tested in combination with the GAT1 selective inhibitors tiagabine
      and LU-32-176B (N-[4,4-bis(4-fluorophenyl)-butyl]-3-hydroxy-4-amino-4,5,6,7
      tetrahydrobenzo[d]isoxazol-3-ol). Additional studies will be required to define a
      role for the other GABA transporters and to further identify the functional
      importance of their demonstrated cellular and regional heterogeneity. A summary
      of these and other issues are discussed in this brief review.

PMID- 15451400
TI  - Activation mechanism of the heterodimeric GABA(B) receptor.
AB  - The GABA(B) receptor was the first heteromeric G-protein coupled receptor (GPCR)
      identified. Indeed, both GABA(B1) and GABA(B2) subunits appear necessary to get a
      functional GABA(B) receptor. Soon after the cloning of both subunits, it was
      demonstrated that GABA(B2) was required for GABA(B1) to reach the cell surface.
      However, even a mutated GABA(B1) able to reach the cell surface is not functional
      alone despite its ability to bind GABA(B) ligands. This clearly demonstrated that
      GABA(B2) is not only required for the correct trafficking of GABA(B1) but also
      for the correct functioning of the receptor. In the present review article, we
      will summarize our actual knowledge of the specific role of each subunit in
      ligand recognition, intramolecular transduction, G-protein activation and
      allosteric modulation. We will show that the GABA(B) receptor is an heterodimer
      (not an hetero-oligomer), that agonists bind in GABA(B1), whereas GABA(B2)
      controls agonist affinity and is responsible for G-protein coupling. Finally, we
      will show that the recently identified positive allosteric modulator CGP7930 acts
      as a direct activator of the heptahelical domain of GABA(B2), being therefore the
      first GABA(B2) ligand identified so far.

PMID- 15451401
TI  - GABA(A) agonists and partial agonists: THIP (Gaboxadol) as a non-opioid analgesic
      and a novel type of hypnotic.
AB  - The GABA(A) receptor system is implicated in a number of central nervous system
      (CNS) disorders, making GABA(A) receptor ligands interesting as potential
      therapeutic agents. Only a few different classes of structures are currently
      known as ligands for the GABA recognition site on the hetero-pentameric GABA(A)
      receptor complex, reflecting the very strict structural requirements for GABA(A)
      receptor recognition and activation. A large number of the compounds showing
      agonist activity at the GABA(A) receptor site are structurally derived from the
      GABA(A) agonists muscimol, THIP (Gaboxadol), or isoguvacine, which we developed
      at the initial stage of the project. Using recombinant GABA(A) receptors,
      functional selectivity has been shown for a number of compounds, including THIP,
      showing subunit-dependent potency and maximal response. The pharmacological and
      clinical activities of THIP probably reflect its potent effects at extrasynaptic
      GABA(A) receptors insensitive to benzodiazepines and containing
      alpha(4)beta(3)delta subunits. The results of ongoing clinical studies on the
      effect of the partial GABA(A) agonist THIP on human sleep pattern show that the
      functional consequences of a directly acting agonist are distinctly different
      from those seen after administration of GABA(A) receptor modulators, such as
      benzodiazepines. In the light of the interest in partial GABA(A) receptor
      agonists as potential therapeutics, structure-activity studies of a number of
      analogues of 4-PIOL, a low-efficacy partial GABA(A) agonist derived from THIP,
      have been performed. In this connection, a series of GABA(A) ligands has been
      developed showing pharmacological profiles ranging from low-efficacy partial
      GABA(A) agonist activity to selective antagonist effect.

PMID- 15451402
TI  - gamma-Aminobutyric acid A receptor subunit mutant mice: new perspectives on
      alcohol actions.
AB  - gamma-Aminobutyric acid A (GABA(A)) receptors are believed to mediate a number of
      alcohol's behavioral actions. Because the subunit composition of GABA(A)
      receptors determines receptor pharmacology, behavioral sensitivity to alcohol
      (ethanol) may depend on which subunits are present (or absent). A number of knock
      out and/or transgenic mouse models have been developed (alpha1, alpha2, alpha5,
      alpha6, beta2, beta3, gamma2S, gamma2L, delta) and tested for behavioral
      sensitivity to ethanol. Here we review the current GABA(A) receptor subunit knock
      out and transgenic literature for ethanol sensitivity, and integrate these
      results into those obtained using quantitative trait loci (QTL) analysis and gene
      expression assays. Converging evidence from these three approaches support the
      notion that different behavioral actions of ethanol are mediated by specific
      subunits, and suggest that new drugs that target specific GABA(A) subunits may
      selectively alter some behavioral actions of ethanol, without altering others.
      Current data sets provide strongest evidence for a role of alpha1-subunits in
      ethanol-induced loss of righting reflex, and alpha5-subunits in ethanol
      stimulated locomotion. However, three-way validation is hampered by the
      incomplete behavioral characterization of many of the mutant mice, and additional
      subunits are likely to be linked to alcohol actions as behavioral testing
      progresses.

PMID- 15451403
TI  - Differential expression of GABA(B(1b)) receptor mRNA in the thalamus of normal
      and monoarthritic animals.
AB  - GABA(B) receptors have been implicated in the plastic changes occurring in the
      spinal cord during the development of chronic inflammatory pain. In this study,
      we evaluated whether the expression of GABA(B(1b)) receptor mRNA is regulated
      supraspinally, namely in the thalamus, as part of the response to chronically
      enhanced noxious input arising from experimental monoarthritis (MA). In situ
      hybridization with [(35)S]-labelled oligonucleotide probes was performed in
      sections of control, 2, 4, 7 and 14 days MA rats' brains (n = 6/group). The
      distribution of GABA(B(1b)) mRNA was determined bilaterally in the ventrobasal
      complex (VB), posterior (Po), centromedial/centrolateral (CM/CL) and reticular
      (Rt) thalamic nuclei. The amount of GABA(B(1b)) mRNA was expressed as times fold
      of background values. In normal animals, values of mRNA expression were very
      similar in VB, Po and CM/CL, ranging from 2.2 +/- 0.2 to 2.7 +/- 0.4 (mean +/-
      S.E.M.) times higher than background levels. No expression of GABA(B(1b)) mRNA
      was found in the Rt of control or MA animals. A significant decrease of 26% at 4
      days, and 37% at 7 days of MA, was observed in the VB contralateral to the
      affected joint. On the contrary, in the Po there was a significant bilateral
      increase at 2 days (38% contralaterally, 25% ipsilaterally), returning to basal
      levels at 4 days MA. No significant changes were observed in CM/CL. These results
      suggest that the expression of GABA(B(1b)) in the VB and Po is regulated by
      noxious input, and might contribute to the functional changes that occur in the
      thalamus during chronic inflammatory pain.

PMID- 15451404
TI  - Altered hippocampal expression of calbindin-D-28k and calretinin in GABA(B(1))
      deficient mice.
AB  - Balb/c GABA(B(1))(-/-) mice develop complex epileptiform activity, including
      spontaneous and audiogenic generalized seizures, 6-8 weeks after birth. The
      neuronal systems involved in these epilepsies have not been identified yet.
      Because the hippocampus is critically involved in epileptiform activity, we now
      investigated whether this brain region exhibits seizure-related alterations.
      Using semi-quantitative immunohistochemistry, we studied the temporal and
      cellular hippocampal expression pattern of two seizure-sensitive calcium-binding
      proteins, calbindin-D-28k and calretinin, in GABA(B(1))(-/-) mice. One month
      after birth, before the onset of overt epileptiform activity, wild-type (WT) and
      GABA(B(1))(-/-) mice exhibit comparable expression profiles for the two calcium
      binding proteins. Three months after birth, once the epileptic phenotype is
      established, we observe clear alterations in the expression of calcium-binding
      proteins in the dentate gyrus area. GABA(B(1))(-/-) mice exhibit a 50% decline in
      the staining intensity of calbindin-D-28k expressing neurons and a 70% increase
      in the number of calretinin-positive neurons when compared to WT littermates. Six
      months after birth, the down-regulation of calbindin-D-28k protein is even more
      pronounced, while the calretinin expression in GABA(B(1))(-/-) mice reverts to
      the pattern seen in WT littermates. Our data demonstrate that the absence of
      functional GABA(B) receptors causes epileptiform activity through a mechanism
      that crucially involves dentate gyrus granule cells, and that this pathological
      activity is accompanied by adaptive changes.

PMID- 15451405
TI  - Affinity of various benzodiazepine site ligands in mice with a point mutation in
      the GABA(A) receptor gamma2 subunit.
AB  - The benzodiazepine binding site of GABA(A) receptors is located at the interface
      of the alpha and gamma subunits. Certain point mutations in these subunits have
      been demonstrated to dramatically reduce the affinity of benzodiazepine binding
      site ligands for these receptors. Recently, mice were generated with a
      phenylalanine (F) to isoleucine (I) substitution at position 77 in the gamma2
      subunit of GABA(A) receptors. Here we tested the potency of 24 benzodiazepine
      binding site ligands from 16 different structural classes for inhibition of
      [(3)H]flunitrazepam binding to brain membranes of these gamma2F77I mice. Results
      indicate that the potency of the classical 1,4-benzodiazepines, of the 1,4
      thienodiazepine clotiazepam, the 1,5-benzodiazepine clobazam, or the
      pyrazoloquinoline CGS 9896 is only 2-7-fold reduced by this gamma2F77I point
      mutation. The potency of the imidazopyrimidines Ru 32698, Ru 33203, and Ru 33356,
      of the imidazoquinoline Ru 31719, or the pyrazolopyridine CGS 20625 is reduced 10
      20-fold, whereas the potency of some imidazobenzodiazepines, beta-carbolines,
      cyclopyrrolones, imidazopyridines, triazolopyridazines, or quinolines is 100-1000
      fold reduced. Interestingly, the extent of potency reduction induced by the
      gamma2F77I point mutation varied within the structural classes of compounds.
      Results support and significantly extend previous observations indicating that
      the residue gamma2F77 is important for high affinity binding of some, but not all
      benzodiazepine site ligands.

PMID- 15451406
TI  - The dietary flavonoids apigenin and (-)-epigallocatechin gallate enhance the
      positive modulation by diazepam of the activation by GABA of recombinant GABA(A)
      receptors.
AB  - The dietary flavonoids apigenin, genistein and (-)-epigallocatechin gallate
      (EGCG) inhibited the activation by GABA (40 microM) of recombinant human
      alpha1beta2gamma2L GABA(A) receptors expressed in Xenopus laevis oocytes with
      IC(50) values of 8, 30 and 15 microM, respectively. Apigenin and genistein also
      acted as GABA antagonists at flumazenil-insensitive alpha1beta2 GABA(A)
      receptors, indicating that they were not acting as negative modulators through
      flumazenil-sensitive benzodiazepine sites on GABA(A) receptors. In addition to
      these GABA(A) antagonist effects, a novel second order modulatory action was
      found for apigenin and EGCG on the first order enhancement of GABA responses by
      diazepam. Apigenin (1 microM) and EGCG (0.1 microM) enhanced the modulatory
      action of diazepam (3 microM) on the activation by GABA (5 microM) of recombinant
      human alpha1beta2gamma2L GABA(A) receptors by up to 22% and 52%, respectively.
      This was not found with genistein, nor was it observed with enhancement by
      allopregnanolone or pentobarbitone.

PMID- 15451407
TI  - Proposal for a basic law of neural communication: response = a(stimulus)(0.5) +
      b.
AB  - A basic law of neural communication is proposed to be: response =
      a(stimulus)(0.5) + b, whether referring to operation of a particular nervous
      system as a whole or to portions thereof, from receptors to effectors. This
      differs from previous formulations in that the exponent is set at a constant
      value of 0.5 rather than being considered to vary from one instance to another.
      Supporting data is presented.

PMID- 15451408
TI  - Association of GRIP1 with a GABA(A) receptor associated protein suggests a role
      for GRIP1 at inhibitory synapses.
AB  - GABA(A) receptors mediate the majority of fast synaptic inhibition in the
      mammalian central nervous system. GABA(A) receptors associate with a number of
      cytosolic proteins important for regulating their function including the GABA(A)
      receptor gamma2 subunit associated protein GABARAP. Here we show GABARAP
      associates with the synaptic PDZ domain containing protein GRIP1. GRIP1 has been
      localized to inhibitory synapses however the role of this protein with respect to
      neuronal inhibition remains unclear. Using in vitro protein interaction assays we
      show that GABARAP interacts directly with PDZ domains 4-6 of GRIP1. Furthermore,
      using coimmunoprecipitation assays we show that GABARAP interacts with GRIP1 in
      vivo. Finally, we show that GRIP1 colocalizes with gamma2 subunit containing
      GABA(A) receptors in cultured hippocampal neurons. Our findings provide evidence
      that GRIP1 can associate with proteins important for regulating GABA(A) receptor
      function and suggest that GRIP1 may play a role at inhibitory synapses.

PMID- 15451409
TI  - The GABA(B2) subunit is critical for the trafficking and function of native
      GABA(B) receptors.
AB  - Studies in heterologous systems have demonstrated that heterodimerisation of the
      two GABA(B) receptor subunits appears to be crucial for the trafficking and
      signalling of the receptor. Gene targeting of the GABA(B1) gene has demonstrated
      that the expression of GABA(B1) is essential for GABA(B) receptor function in the
      central nervous system (CNS). However, the contribution of the GABA(B2) subunit
      in the formation of native GABA(B) receptors is still unclear, in particular
      whether other proteins can substitute for this subunit. We have created a
      transgenic mouse in which the endogenous GABA(B2) gene has been mutated in order
      to express a C-terminally truncated version of the protein. As a result, the
      GABA(B1) subunit does not reach the cell surface and concomitantly both pre- and
      post-synaptic GABA(B) receptor functions are abolished. Taken together with
      previous gene deletion studies for the GABA(B1) subunit, this suggests that
      classical GABA(B) function in the brain is exclusively mediated by GABA(B1/2)
      heteromers.

PMID- 15451410
TI  - My close encounter with GABA(B) receptors.
AB  - In this review, I summarize the sequence of events involved in characterizing the
      functional role of GABA(B) receptors in the CNS and their involvement in synaptic
      transmission. The story was launched with the realization that baclofen was a
      selective agonist of GABA(B) receptors. This lead to the discovery in the CNS
      that GABA(B) receptor activation could result in a presynaptic inhibition of
      transmitter release as well as a postsynaptic increase in potassium conductance.
      Based on this information, it was found that GABA also activated a potassium
      conductance. A role for GABA(B) receptors in synaptic transmission was suggested
      by the fact that activation of GABAergic interneurons could generate a slow IPSP
      mediated by an increase in potassium conductance. To link this slow IPSP to
      GABA(B) receptors required a selective GABA(B) antagonist. Phaclofen was the
      first antagonist developed and was found to antagonize the action of baclofen and
      the GABA(A) independent action of GABA. Most importantly, it blocked the slow
      IPSP. The properties of GABA(A) and GABA(B) IPSPs are remarkably different.
      GABA(A) IPSPs powerfully inhibit neurons and rapidly curtail excitatory inputs.
      This greatly enhances the precision of excitatory synaptic transmission. GABA(B)
      IPSPs are recruited with repetitive and synchronous activity and are postulated
      to modulate the rhythmic network activity of cortical tissue.

PMID- 15451411
TI  - Fishing for allosteric sites on GABA(A) receptors.
AB  - GABA(A) receptors have structural and functional homology with a super-family of
      cys-loop ligand-gated ion channel receptors including the nicotinic acetylcholine
      receptors. Amino acid residues involved in ligand-binding pockets are homologous
      among super-family members, leading to the multiple-loop model of binding sites
      situated at subunit interfaces, validated by structural studies on the nicotinic
      acetylcholine receptor and water-soluble snail acetylcholine binding protein.
      This article will briefly review the literature on the agonist binding sites on
      the receptor super-family, and then describe the current situation for attempts
      to identify sites for allosteric modulators on the GABA(A) receptors. A
      combination of mutagenesis and photoaffinity labeling with anesthetic ligands has
      given some leads in this endeavor. Current work by others and ourselves focuses
      on three putative sites for modulators: (1) within the ion channel domain TM2,
      near the extracellular end; (2) the agonist binding sites and homologous pockets
      at other subunit interfaces of the pentameric receptor; and (3) on the linker
      region stretching from the agonist site loop C to the top of the TM1 region. It
      is likely that concrete structural information will be forthcoming soon.

PMID- 15451412
TI  - Specific GABA(A) circuits in brain development and therapy.
AB  - GABAergic interneurons are highly diverse and operate with a corresponding
      diversity of GABA(A) receptor subtypes in controlling behaviour. In this article,
      we review the significance of GABA(A) receptor heterogeneity for neural circuit
      development and central nervous system pharmacology. GABA(A) receptor subtypes
      were identified as selective targets for behavioural actions of benzodiazepines
      and of selected intravenous anesthetic agents using point mutations which render
      a specific receptor subtype insensitive to the action of the respective drugs and
      also by novel subtype-selective ligands. The pharmacological separation of
      anxiolysis and sedation guides the development of novel anxiolytics, while
      inverse agonism at extrasynaptic GABA(A) receptors involved in learning and
      memory is currently being evaluated as a novel therapeutic principle for
      symptomatic memory enhancement.

PMID- 15451413
TI  - The intriguing Ca2+ requirement of calpain activation.
AB  - Mammalian ubiquitous micro- and m-calpains, as well as their Drosophila homologs,
      Calpain A and Calpain B, are Ca(2+)-activated cytoplasmic proteases that act by
      limited proteolysis of target proteins. Calpains are thought to be part of many
      cellular signaling pathways. These enzymes, however, require such high Ca(2+)
      concentration for half-maximal activation in vitro, [Ca(2+)](0.5), that hardly
      ever occurs in intact cells. This major dilemma has pervaded the literature on
      calpains for decades. In this paper several considerations are put forward that
      challenge the orthodox view and envisage mechanisms that may govern calpain
      action in vivo. The "unphysiologically" high Ca(2+) demand for activation may
      turn out to be an evolutionarily adjusted safety device.

PMID- 15451414
TI  - Analysis of tryptophan surface accessibility in proteins by MALDI-TOF mass
      spectrometry.
AB  - Surface accessible amino acids can play an important role in proteins. They can
      participate in enzyme's active center structure or in specific intermolecular
      interactions. Thus, the information about selected amino acids' surface
      accessibility can contribute to the understanding of protein structure and
      function. In this paper, we present a simple method for surface accessibility
      mapping of tryptophan side chains by their chemical modification and
      identification by MALDI-TOF mass spectrometry. The reaction with 2-hydroxy-5
      nitrobenzyl bromide, a common and highly specific covalent modification of
      tryptophan, seems to be very useful for this purpose. The method was tested on
      four model proteins with known spatial structure. In the native proteins (1) only
      surface accessible tryptophan side chains were found to react with the
      modification agent and (2) no buried one was found to react at lower reagent
      concentrations. These results indicate that the described method can be a potent
      tool for identification of surface-located tryptophan side chain in a protein of
      unknown conformation.

PMID- 15451415
TI  - Solid-state 23Na NMR determination of the number and coordination of sodium
      cations bound to Oxytricha nova telomere repeat d(G4T4G4).
AB  - We report a solid-state (23)Na NMR study of the bound sodium cations in a G
      quadruplex formed by Oxytricha nova telomere DNA repeat, d(G(4)T(4)G(4)) (Oxy
      1.5). Using a 2D multiple-quantum magic-angle spinning (23)Na NMR method, we
      observed three sodium cations residing inside the quadruplex channel of the Na(+)
      form of Oxy-1.5. Each of these sodium cations is sandwiched between two G
      quartets. We found no evidence for sodium cations in the T(4) loop region. For
      comparison, solid-state (15)N MAS NMR spectra were also obtained for the
      (15)NH(4)(+) form of Oxy-1.5. The insufficient resolution in the (15)N MAS NMR
      spectra did not permit determination of the number of NH(4)(+) ions inside the
      quadruplex channel. The solid-state (23)Na and (15)N NMR spectra for Oxy-1.5 were
      also compared with those obtained for guanosine 5'-monophosphate.

PMID- 15451416
TI  - A role for ZnT-1 in regulating cellular cation influx.
AB  - The ZnTs are a growing family of proteins involved in lowering or sequestration
      of cellular zinc. Using fluorescent measurements of zinc transport we have
      addressed the mechanism of action of the most ubiquitously expressed member of
      this family, ZnT-1. This protein has been shown to lower levels of intracellular
      zinc though the mechanism has remained elusive. The rate of zinc efflux in HEK293
      cells expressing ZnT-1 was not accelerated in comparison to control cells,
      suggesting that ZnT-1 may be involved in regulating influx rather than efflux of
      zinc. Co-expression of the L-type calcium channel, a major route for zinc influx,
      and ZnT-1 resulted in a 3-fold reduction in the rate of zinc influx in HEK293 and
      PC-12 cells, indicating that ZnT-1 modulates zinc permeation through this
      channel. Immunoblot analysis indicates that ZnT-1 expression does not modulate
      LTCC expression. Our findings therefore indicate that ZnT-1 modulates the
      permeation of cations through LTCC, thereby, regulating cation homeostasis
      through this pathway. Furthermore, ZnT-1 may play a role in cellular ion
      homeostasis and thereby confer protection against pathophysiological events
      linked to cellular Ca(2+) or Zn(2+) permeation and cell death.

PMID- 15451417
TI  - Tyrosine residues modification studied by MALDI-TOF mass spectrometry.
AB  - Amino acid residue-specific reactivity in proteins is of great current interest
      in structural biology as it provides information about solvent accessibility and
      reactivity of the residue and, consequently, about protein structure and possible
      interactions. In the work presented tyrosine residues of three model proteins
      with known spatial structure are modified with two tyrosine-specific reagents:
      tetranitromethane and iodine. Modified proteins were specifically digested by
      proteases and the mass of resulting peptide fragments was determined using matrix
      assisted laser desorption/ionisation time-of-flight mass spectrometry. Our
      results show that there are only small differences in the extent of tyrosine
      residues modification by tetranitromethane and iodine. However, data dealing with
      accessibility of reactive residues obtained by chemical modifications are not
      completely identical with those obtained by nuclear magnetic resonance and X-ray
      crystallography. These interesting discrepancies can be caused by local molecular
      dynamics and/or by specific chemical structure of the residues surrounding.

PMID- 15451418
TI  - Rab27b localizes to zymogen granules and regulates pancreatic acinar exocytosis.
AB  - To understand the function of pancreatic zymogen granules, we performed a
      proteomics analysis to identify ZG membrane components. Here we report the
      identification of Rab27b through this proteomics study and validate its role in
      granule function. MALDI-MS peptide mass fingerprint was matched to rat Rab27b
      with 43% sequence coverage, and the identification was also confirmed by tandem
      mass spectrometry. The localization of Rab27b on ZGs was confirmed by Western
      blotting and immunocytochemistry. To examine the function of Rab27b in acinar
      secretion, we overexpressed wild type and mutant Rab27b protein in pancreatic
      acini using recombinant adenoviruses. Wild type Rab27b had no effect on amylase
      secretion, while Rab27b Q78L enhanced, and Rab27b N133I inhibited, CCK-induced
      amylase release by 92+/-13% and 53+/-8%, respectively. This enhancement and
      inhibition occurred at all points on the CCK dose-response curve and over a 30min
      time course. These results demonstrate that Rab27b is present on ZGs and plays an
      important role in regulating acinar exocytosis.

PMID- 15451419
TI  - Heat-induced oligomerization of gp96 occurs via a site distinct from substrate
      binding and is regulated by ATP.
AB  - Gp96 (GRP94) is a dimeric glycoprotein and is the endoplasmic reticulum
      representative of the hsp90 family of molecular chaperones. In addition to the
      protein substrates it chaperones, gp96 binds weakly to both peptides and ATP, and
      has been shown to self-assemble into discrete oligomers upon heat shock at 50
      degrees C, although physiological roles for these phenomena have not been well
      established. Our studies indicate that gp96 homooligomerizes irreversibly in
      vitro at temperatures as low as 42 degrees C and could involve pre-dissociation
      of dimers to monomers. Oligomerization is inhibited significantly by ATP;
      hydrolysis is not required, since ADP, ATP-gamma-S, and NECA inhibit self
      assembly equally well. Peptide ligands do not competitively inhibit gp96 self
      assembly and, in fact, bind to all oligomeric species, including the dimer.
      Together, these findings suggest that (1) heat-enhanced chaperone activity does
      not reside in oligomers per se, and (2) the regions of gp96 involved in peptide
      binding and oligomerization are distinct.

PMID- 15451420
TI  - Isolation of a dinoflagellate mitotic cyclin by functional complementation in
      yeast.
AB  - Dinoflagellates are protists with permanently condensed chromosomes that lack
      histones and whose nuclear membrane remains intact during mitosis. These unusual
      nuclear characters have suggested that the typical cell cycle regulators might be
      slightly different than those in more typical eukaryotes. To test this, a cyclin
      has been isolated from the dinoflagellate Gonyaulax polyedra by functional
      complementation in cln123 mutant yeast. This GpCyc1 sequence contains two cyclin
      domains in its C-terminal region and a degradation box typical of mitotic
      cyclins. Similar to other dinoflagellate genes, GpCyc1 has a high copy number,
      with approximately 5000 copies found in the Gonyaulax genome. An antibody raised
      against the N-terminal region of the GpCYC1 reacts with a 68kDa protein on
      Western blots that is more abundant in cell cultures enriched for G2-phase cells
      than in those containing primarily G1-phase cells, indicating its cellular level
      follows a pattern expected for a mitotic cyclin. This is the first report of a
      cell cycle regulator cloned and sequenced from a dinoflagellate, and our results
      suggest control of the dinoflagellate cell cycle will be very similar to that of
      other organisms.

PMID- 15451421
TI  - In vitro effects of strontium ranelate on the extracellular calcium-sensing
      receptor.
AB  - The extracellular calcium-sensing receptor (CaSR) is activated by divalent
      cations and might mediate some of the effects of strontium ranelate, a new drug
      for the prevention and treatment of post-menopausal osteoporosis. Here, we showed
      that the maximal effect of Sr(2+) was comparable to that observed for Ca(2+) for
      both the cloned rat CaSR expressed in Chinese hamster ovary [CHO(CaSR)] cells and
      the mouse CaSR constitutively expressed in AtT-20 cells as measured by the
      accumulation of [(3)H]inositol phosphates (IP) resulting from CaSR activation.
      Strontium ranelate also displayed comparable agonist activity for the CaSR in
      both cell lines. Sodium ranelate did not stimulate the IP response in CHO(CaSR)
      cells. The IP response resulting from activation of other G-protein-coupled
      receptors was potentiated by Sr(2+), suggesting that entry of Sr(2+) into the
      cells might influence phospholipase C activity. Modulation of the CaSR activity
      in bone cells by strontium ranelate may contribute to its reported
      antiosteoporotic effects.

PMID- 15451422
TI  - Molecular docking of four beta-amyloid1-42 fragments on the alpha7 nicotinic
      receptor: delineating the binding site of the Abeta peptides.
AB  - Three-dimensional structures of the complexes between the Abeta(1-42) fragments
      Abeta(1-11), Abeta(10-20), Abeta(12-28), and Abeta(22-35) and the alpha7
      nicotinic receptor were obtained with the aid of the ESCHER program. Furthermore,
      short high-temperature molecular dynamics simulations in vacuo were employed to
      relax the complexes and allow the peptides to accommodate in the binding site.
      The final models have shown that Abeta peptides do bind on the same site, which
      is delineated by loop C of one subunit and the loops 62-74 and G of the adjacent
      subunit on the receptor. This finding is supported by previous experimental and
      theoretical data, and should help one to obtain a better and more detailed
      structural information about the activity of the Abeta peptides and their
      repercussion in the disorders at molecular level, which are characteristic of the
      Alzheimer's disease.

PMID- 15451423
TI  - ATR-dependent phosphorylation of ATRIP in response to genotoxic stress.
AB  - PI-kinase-related protein kinase ATR forms a complex with ATRIP and plays pivotal
      roles in maintaining genome integrity. When DNA is damaged, the ATR-ATRIP complex
      is recruited to chromatin and is activated to transduce the checkpoint signal,
      but the precise kinase activation mechanism remains unknown. Here, we show that
      ATRIP is phosphorylated in an ATR-dependent manner after genotoxic stimuli. The
      serine 68 and 72 residues are important for the phosphorylation in vivo and are
      required exclusively for direct modification by ATR in vitro. Using phospho
      specific antibody, we demonstrated that phosphorylated ATRIP accumulates at foci
      induced by DNA damage. Moreover, the loss of phosphorylation does not lead to
      detectable changes in the relocalization of ATRIP to nuclear foci nor in the
      activation of downstream effector proteins. Collectively, our results suggest
      that the ATR-mediated phosphorylation of ATRIP at Ser-68 and -72 is dispensable
      for the initial response to DNA damage.

PMID- 15451424
TI  - Insulin-like growth factor-1 contributes to neovascularization in age-related
      macular degeneration.
AB  - Choroidal neovascularization (CNV) is a debilitating complication of age-related
      macular degeneration and a leading cause of vision loss. Along with other
      angiogenic factors like vascular endothelial growth factor (VEGF), insulin-like
      growth factor (IGF)-1 and its receptor, IGF-1R, have been implicated in CNV. IGF
      1 is produced in neurons and retinal pigment epithelium (RPE) but its targets and
      impact in CNV are not understood. IGF-1 immunoreactivity was abundant throughout
      surgically isolated human CNV tissues and RPE cells were immunopositive for IGF
      1R. Cultured RPE cells obtained from CNV tissues expressed IGF-1R. IGF-1
      stimulation of cultured cells from CNV tissues induced monophasic sustained rises
      in intracellular free Ca(2+). VEGF concentration in the medium of unstimulated
      RPE cell cultures from CNV tissues increased with time to a steady-state (8h)
      which was increased twofold by IGF-1 stimulation. Thus, in RPE cells IGF-1
      stimulates the second messenger Ca(2+) and increases VEGF secretion which, in
      turn, induces neovascularization.

PMID- 15451425
TI  - Structural and functional characterization of "laboratory evolved" cytochrome
      P450cam mutants showing enhanced naphthalene oxygenation activity.
AB  - To elucidate molecular mechanisms for the enhanced oxygenation activity in the
      three mutants of cytochrome P450cam screened by 'laboratory evolution' [Nature
      399 (1999) 670], we purified the mutants and characterized their functional and
      structural properties. The electronic absorption and resonance Raman spectra
      revealed that the structures of heme binding site of all purified mutants were
      quite similar to that of the wild-type enzyme, although the fraction of the
      inactivated form, called "P420," was increased. In the reaction with H(2)O(2),
      only trace amounts of the naphthalene hydroxylation product were detected by gas
      chromatography. We, therefore, conclude that the three mutants do not exhibit
      significant changes in the structural and functional properties from those of
      wild-type P450cam except for the stability of the axial ligand in the reduced
      form. The enhanced fluorescence in the whole-cell assay would reflect enhancement
      in the oxygenation activity below the detectable limit of the gas chromatography
      and/or contributions of other reactions catalyzed by the heme iron.

PMID- 15451426
TI  - Identification of a novel BRMS1-homologue protein p40 as a component of the
      mSin3A/p33(ING1b)/HDAC1 deacetylase complex.
AB  - Repression of gene transcription is mediated by histone deacetylases containing
      repressor-co-repressor complexes, which are recruited to promoters of target
      genes via interactions with sequence-specific transcription factors. The
      mammalian Sin3A co-repressor complex contains a core of at least seven proteins
      including the pRb-interacting protein RBP1 and a putative tumor suppressor
      p33(ING1b). By biochemical purification and mass spectrometry, we have identified
      a novel component p40 from this complex. p40 bears homology to both yeast Sds3, a
      component of yeast histone deacetylase complexes, and its mammalian homologue
      mSds3. The p40-associated complex purified from human cells shows a strong
      histone deacetylase activity. When tethered to a Gal-DNA binding domain, the Gal
      p40 is able to significantly repress transcription of a Gal-luciferase promoter.
      Interestingly, database analysis reveals that p40 is also highly homologous to
      BRMS1, a breast carcinoma metastasis suppressor, and overexpression of p40 in
      human cells can significantly inhibit cell growth. Thus, our data indicate that
      p40 may be critically involved in transcription repression of cell growth
      associated gene expression by recruiting the HDAC1 deacetylase complex.

PMID- 15451427
TI  - Monoclonal antibodies against LDL progressively oxidized by myeloperoxidase react
      with ApoB-100 protein moiety and human atherosclerotic lesions.
AB  - Oxidized-LDL are involved in atherosclerosis pathogenesis, while the production
      of anti-ox-LDL monoclonal antibodies is critical for the development of
      diagnostic tools. This work reports the production of four monoclonal antibodies
      raised against human LDL, oxidized at different levels by the myeloperoxidase
      system. Characterization of these monoclonal antibodies showed that they do not
      cross-react with neither native LDL, VLDL nor hydrogen peroxide or Cu(2+)
      oxidized LDL. Three of these antibodies recognize an epitope restricted to the
      protein moiety of mildly oxidized LDL, whereas the fourth antibody was partly
      dependent on the lipid presence of strongly oxidized LDL. All the antibodies were
      shown to react with human atherosclerotic lesions.

PMID- 15451428
TI  - 1.8A X-ray structure of C95M/C1095F double mutant of tethered HIV-1 protease
      dimer complexed with acetyl pepstatin.
AB  - Under the selection pressure of drugs, mutations appear in HIV-1 protease even at
      the sites, which are conserved in the untreated individuals. Cysteine 95 is a
      highly conserved residue and is believed to be involved in regulation of HIV-1
      protease. In some of the virus isolates from patients undergoing heavy treatment
      with anti-HIV protease drugs, C95F mutation has appeared. The present study
      reports 1.8A X-ray structure of C95M/C1095F double mutant of tethered HIV-1
      protease dimer complexed with acetyl pepstatin. It is found that in this mutant,
      dimer interface has become more rigid and that the packing at the interface of
      terminal and core domains is altered. These alterations may be relevant to C95F
      mutation conferring drug resistance to HIV-1 protease.

PMID- 15451429
TI  - Pharmacological activity of DTPA linked to protein-based drug carrier systems.
AB  - The chelating agent diethylenetriaminepentaacetic acid (DTPA) inhibits human
      cytomegalovirus replication. Since chelating agents are known to exhibit anti
      cancer effects, DTPA-induced cytotoxicity was evaluated in breast cancer cells
      (MCF-7) and neuroblastoma cells (UKF-NB-3). DTPA inhibited cancer cell growth in
      threefold lower concentrations compared to human foreskin fibroblasts (HFF).
      Antiviral and anti-cancer activity of chelating agents is caused by intracellular
      complexation of metal ions. DTPA, an extracellular chelator, was covalently
      coupled to human serum albumin (HSA) molecules, HSA nanoparticles (HSA-NP),
      gelatin type B (GelB) molecules, and GelB nanoparticles (GelB-NP) to increase
      cellular uptake. Coupling of DTPA to drug carrier systems increased its cytotoxic
      and antiviral activity by 5- to 8-fold. Confocal laser scanning microscope
      examination revealed uptake of DTPA-HSA-NP in UKF-NB-3 cells and HFF. Therefore,
      coupling of DTPA to protein-based drug carrier systems increases its antiviral
      and anti-cancer activity probably by mediating cellular uptake.

PMID- 15451430
TI  - Pancreatic cancer stimulates pancreatic stellate cell proliferation and TIMP-1
      production through the MAP kinase pathway.
AB  - Pancreatic adenocarcinoma is characterized by an intense desmoplastic reaction
      that surrounds the tumor. Pancreatic stellate cells (PSCs) are thought to be
      responsible for production of this extracellular matrix. When activated, PSCs
      have a myofibroblast phenotype and produce not only components of the
      extracellular matrix including collagen, fibronectin, and laminin, but also
      matrix metalloproteinases and tissue inhibitors of metalloproteinases (TIMPs).
      Since PSCs are found in the stroma surrounding human pancreatic adenocarcinoma,
      we postulate that pancreatic cancer could impact PSC proliferation and TIMP-1
      production. Rat PSCs were isolated and cultured. Isolated PSCs were exposed to
      PANC-1 conditioned medium (CM) and proliferation, activation of the mitogen
      activated protein (MAP) kinase pathway, and TIMP-1 gene induction were
      determined. Exposure to PANC-1 CM increased PSC DNA synthesis, cell number, and
      TIMP-1 mRNA (real-time PCR) as well as activating the extracellular-regulated
      kinase (ERK) 1/2. Inhibition of ERK 1/2 phosphorylation (U0126) prevented the
      increases in growth and TIMP-1 expression. PANC-1 CM stimulates PSC proliferation
      and TIMP-1 through the MAP kinase (ERK 1/2) pathway.

PMID- 15451431
TI  - Dickkopf-1 antagonizes Wnt signaling independent of beta-catenin in human
      mesothelioma.
AB  - Dickkopf-1 (Dkk-1) is a secreted protein that acts as a potent inhibitor of the
      Wnt signal transduction pathway. It is thought that the antagonistic effect of
      Dkk-1 is specific to the canonical (Wnt/beta-catenin) pathway. In this study, we
      demonstrate that restoration of Dkk-1 expression suppresses cell growth and
      induces apoptotic cell death in beta-catenin-deficient mesothelioma cell lines
      H28 and MS-1. Furthermore, we found that a small-molecule inhibitor of JNK
      inhibited the apoptosis induced by Dkk-1 overexpression in these cells. Together,
      our data suggest that Dkk-1 may be able to antagonize Wnt signaling and exert its
      tumor suppressive effects through beta-catenin-independent non-canonical pathways
      (i.e., the Wnt/JNK pathway).

PMID- 15451432
TI  - Fesselin is a target protein for calmodulin in a calcium-dependent manner.
AB  - Fesselin is a basic protein isolated from smooth muscle which binds G-actin and
      accelerates its polymerization as well as cross-links assembled filaments [J.
      Muscle Res. Cell Motil. 20 (1999) 539; Biochemistry 40 (2001) 14252]. In this
      report experimental evidence is provided for the first time proving that fesselin
      can interact with calmodulin in a Ca(2+)-dependent manner in vitro. Using ion
      exchange, followed by calmodulin-affinity chromatography, enabled us to simplify
      and shorten the fesselin preparation procedure and increase its yield by about
      three times in comparison to the procedure described by Leinweber et al. [J.
      Muscle Res. Cell Motil. 20 (1999) 539]. Fesselin interaction with dansyl-labelled
      calmodulin causes a 2-fold increase in maximum fluorescence intensity of the
      fluorophore and a 21nm blue shift of the spectrum. The transition of complex
      formation between fesselin and calmodulin occurs at submicromolar concentration
      of calcium ions. The dissociation constant of fesselin Ca(2+)/calmodulin
      complexes amounted to 10(-8)M. The results suggest the existence of a direct link
      between Ca(2+)/calmodulin and fesselin at the level of actin cytoskeleton
      dynamics in smooth muscle.

PMID- 15451433
TI  - Structures of wild-type and P28L/Y173F tryptophan synthase alpha-subunits from
      Escherichia coli.
AB  - The alpha-subunit of tryptophan synthase (alphaTS) catalyzes the cleavage of
      indole-3-glycerol phosphate to glyceraldehyde-3-phosphate and indole, which is
      used to yield the amino acid tryptophan in tryptophan biosynthesis. Here, we
      report the first crystal structures of wild-type and double-mutant P28L/Y173F
      alpha-subunit of tryptophan synthase from Escherichia coli at 2.8 and 1.8A
      resolution, respectively. The structure of wild-type alphaTS from E. coli was
      similar to that of the alpha(2)beta(2) complex structure from Salmonella
      typhimurium. As compared with both structures, the conformational changes are
      mostly in the interface of alpha- and beta-subunits, and the substrate binding
      region. Two sulfate ions and two glycerol molecules per asymmetric unit bind with
      the residues in the active sites of the wild-type structure. Contrarily, double
      mutant P28L/Y173F structure is highly closed at the window for the substrate
      binding by the conformational changes. The P28L substitution induces the exposure
      of hydrophobic amino acids and decreases the secondary structure that causes the
      aggregation. The Y173F suppresses to transfer a signal from the alpha-subunit
      core to the alpha-subunit surface involved in interactions with the beta-subunit
      and increases structural stability.

PMID- 15451434
TI  - Quantum chemical analysis explains hemagglutinin peptide-MHC Class II molecule
      HLA-DRbeta1*0101 interactions.
AB  - We present a new method to explore interactions between peptides and major
      histocompatibility complex (MHC) molecules using the resultant vector of the
      three principal multipole terms of the electrostatic field expansion. Being that
      molecular interactions are driven by electrostatic interactions, we applied
      quantum chemistry methods to better understand variations in the electrostatic
      field of the MHC Class II HLA-DRbeta1*0101-HA complex. Multipole terms were
      studied, finding strong alterations of the field in Pocket 1 of this MHC
      molecule, and weak variations in other pockets, with Pocket 1>>Pocket 4>Pocket 9
      approximately Pocket 7>Pocket 6. Variations produced by "ideal" amino acids and
      by other occupying amino acids were compared. Two types of interactions were
      found in all pockets: a strong unspecific one (global interaction) and a weak
      specific interaction (differential interaction). Interactions in Pocket 1, the
      dominant pocket for this allele, are driven mainly by the quadrupole term,
      confirming the idea that aromatic rings are important in these interactions.
      Multipolar analysis is in agreement with experimental results, suggesting quantum
      chemistry methods as an adequate methodology to understand these interactions.

PMID- 15451435
TI  - Oligomerization of the proteolytic products is an intrinsic property of prion
      proteins.
AB  - In the present study we show that the oligomerization of the proteolytic products
      is an intrinsic property of prion proteins. No such oligomerization was observed
      for the proteolytic products of other proteins after identical treatment. The
      rate of enzymatic hydrolysis of recombinant human (rhPrP) (23-231) and golden
      hamster (rmaPrP) (23-231) prion proteins as well as that of rmaPrP (90-231),
      corresponding to the infectious fragment of the scrapie form, drastically
      increases in the presence of chemical chaperones like dimethyl sulphoxide and
      glycerol as well as in 20% ethanol. A bacterial proteinase, termed "prionase,"
      has a superior efficiency towards prion proteins in comparison to proteinase K
      and subtilisin DY. The early steps in the proteolysis by the latter enzymes have
      been identified. The results have potential impact on the treatment of scrapie
      infected materials.

PMID- 15451436
TI  - Telomerase-transduced osteoarthritic fibroblast-like synoviocyte cell line.
AB  - To examine whether the life span of fibroblast-like synoviocytes (FLSs) can be
      extended and to establish FLS cell lines that preserve the characteristics of
      primary FLSs, we introduced human catalytic subunit of telomerase (hTERT) gene
      into human osteoarthritic (OA) FLSs. Two hTERT-transduced clonal cell lines were
      established and one line, hTERT-OA FLS 13A, was characterized. The hTERT-OA FLS
      13A cells have a morphology similar to that of the parental untransduced cells
      and a population-doubling time similar to that of the parental cells of early
      passages. While the parental untransduced OA FLSs reached senescence after 100
      days in culture, the hTERT-OA FLS 13A cells continued to grow at a population
      doubling rate of once in about every 2-3 days. The hTERT-OA 13A cells have so far
      grown in culture beyond 450 days and maintained the same growth rate.
      Furthermore, the hTERT-OA FLS 13A cells preserved their sensitivity and response
      to the treatment with basic calcium phosphate crystals and interleukin-1beta. In
      conclusion, exogenous expression of telomerase represents a way to extend the
      life span of human FLSs and telomerase-transduced FLS cells offer a promising
      tool for gene regulation, cell-based assay, cell transplantation-based gene
      therapy, and tissue engineering research and development.

PMID- 15451437
TI  - Immediate early gene X-1 interacts with proteins that modulate apoptosis.
AB  - Immediate early gene X-1 (IEX-1) modulates apoptosis, cellular growth, mechanical
      strain-induced cardiac hypertrophy, and vascular intimal hyperplasia. To
      determine how IEX-1 alters apoptosis, we performed yeast two-hybrid studies using
      IEX-1 as the "bait" protein, and examined interactions between IEX-1 and proteins
      expressed by a human kidney cDNA expression library. We found that IEX-1
      interacts with several proteins of which at least four are known to play a role
      in the regulation of apoptosis: (1) calcium-modulating cyclophilin ligand; (2)
      tumor necrosis factor-related apoptosis-inducing ligand (tumor necrosis factor
      superfamily, member 10); (3) ML-1 myeloid cell leukemia gene encoded protein; and
      (4) BAT3, a gene present in the major histo-compatibility complex. Our data
      suggest that IEX-1 may regulate apoptosis by directly interacting with various
      proteins involved in the control of apoptotic pathways.

PMID- 15451438
TI  - Augmented heme oxygenase-1 induces prostaglandin uptake via the prostaglandin
      transporter in micro-vascular endothelial cells.
AB  - Previous studies show that expression of heme oxygenase-1 (HO-1) in endothelial
      cells results in decreased cyclooxygenase expression and prostaglandin (PG)
      levels through limiting heme availability. Regulation of PGs, important
      inflammatory mediators, may contribute to the anti-inflammatory potential of HO
      1. Here we examine the effects of HO-1 expression on PG clearance via the
      prostaglandin transporter (PGT). Endothelial cells expressing human HO-1 via
      retroviral transfer exhibit approximately 7-fold higher levels of PGT RNA and
      equivalently elevated uptake of [(3)H]PGE(2). The pattern and extent of uptake
      and the substrate inhibitory constants of PGE(2), PGF(2alpha), and thromboxane
      B(2) are similar to those of cloned PGT. Treatment of cells with stannous
      chloride, an inducer of HO-1, results in increased expression of PGT while
      incubation of cells expressing human HO-1 with stannic mesophorphyrin, a
      substrate inhibitor of HO-1, decreases PG uptake. Therefore, PG clearance via PGT
      may contribute to the cellular regulation of PG levels by HO-1.

PMID- 15451439
TI  - ERp57 is present in STAT3-DNA complexes.
AB  - STAT3 has been found constitutively activated in M14 melanoma cell line, as
      previously found in other melanoma cells. Using EMSA, DNA affinity experiments,
      and chromatin immunoprecipitation, STAT3 was found in M14 to bind the alpha2
      macroglobulin gene enhancer in association with the protein disulfide isomerase
      isoform ERp57. The two proteins have also been found to be associated when bound
      to the SIE sequence in HepG2 cells stimulated by IL-6. In both cases an anti
      ERp57 antibody hinders the binding of STAT3 to its consensus sequence on DNA,
      indicating that ERp57 is a necessary component of the DNA-bound STAT3 complex.
      Considering the functional association of the two proteins, the overexpression of
      ERp57 observed in a variety of transformed cells might be relevant to the
      oncogenic properties of STAT3.

PMID- 15451440
TI  - Inhibitors of protein phosphatases 1 and 2A differentially prevent intrinsic and
      extrinsic apoptosis pathways.
AB  - Inhibitors of serine/threonine protein phosphatases can inhibit apoptosis. We
      investigated which protein phosphatases are critical for this protection using
      calyculin A, okadaic acid, and tautomycin. All three phosphatase inhibitors
      prevented anisomycin-induced apoptosis in leukemia cell models. In vitro,
      calyculin A does not discriminate between PP1 and PP2A, while okadaic acid and
      tautomycin are more selective for PP2A and PP1, respectively. Increased
      phosphorylation of endogenous marker proteins was used to define concentrations
      that inhibited each phosphatase in cells. Concentrations of each inhibitor that
      prevented anisomycin-induced apoptosis correlated with inhibition of PP2A. The
      inhibitors prevented Bax translocation to mitochondria, indicating inhibition
      upstream of mitochondria. Tautomycin and calyculin A, but not okadaic acid, also
      prevented apoptosis induced through the CD95/Fas death receptor, and this
      protection correlated with inhibition of PP1. The inhibitors prevented Fas
      receptor oligomerization, FADD recruitment, and caspase 8 activation. The
      differential effects of PP1 and PP2A in protection from death receptor and
      mitochondrial-mediated pathways of death, respectively, may help one to define
      critical steps in each pathway, and regulatory roles for serine/threonine
      phosphatases in apoptosis.

PMID- 15451441
TI  - A protein delivery system: biodegradable alginate-chitosan-poly(lactic-co
      glycolic acid) composite microspheres.
AB  - In the present study we developed alginate-chitosan-poly(lactic-co-glycolic acid)
      (PLGA) composite microspheres to elevate protein entrapment efficiency and
      decrease its burst release. Bovine serum albumin (BSA), which used as the model
      protein, was entrapped into the alginate microcapsules by a modified
      emulsification method in an isopropyl alcohol-washed way. The rapid drug releases
      were sustained by chitosan coating. To obtain the desired release properties, the
      alginate-chitosan microcapsules were further incorporated in the PLGA to form the
      composite microspheres. The average diameter of the composite microcapsules was
      31+/-9microm and the encapsulation efficiency was 81-87%, while that of
      conventional PLGA microspheres was just 61-65%. Furthermore, the burst releases
      at 1h of BSA entrapped in composite microspheres which containing PLGA (50:50)
      and PLGA (70:30) decreased to 24% and 8% in PBS, and further decreased to 5% and
      2% in saline. On the contrary, the burst releases of conventional PLGA
      microspheres were 48% and 52% in PBS, respectively. Moreover, the release
      profiles could be manipulated by regulating the ratios of poly(lactic acid) to
      poly(glycolic acid) in the composite microspheres.

PMID- 15451442
TI  - DNA polymerase lambda can elongate on DNA substrates mimicking non-homologous end
      joining and interact with XRCC4-ligase IV complex.
AB  - Non-homologous end joining (NHEJ) is one of two pathways responsible for the
      repair of double-strand breaks in eukaryotic cells. The mechanism involves the
      alignment of broken DNA ends with minimal homology, fill in of short gaps by DNA
      polymerase(s), and ligation by XRCC4-DNA ligase IV complex. The gap-filling
      polymerase has not yet been positively identified, but recent biochemical studies
      have implicated DNA polymerase lambda (pol lambda), a novel DNA polymerase that
      has been assigned to the pol X family, in this process. Here we demonstrate that
      purified pol lambda can efficiently catalyze gap-filling synthesis on DNA
      substrates mimicking NHEJ. By designing two truncated forms of pol lambda, we
      also show that the unique proline-rich region in pol lambda plays a role in
      limiting strand displacement synthesis, a feature that may help its participation
      in in vivo NHEJ. Moreover, pol lambda interacts with XRCC4-DNA ligase IV via its
      N-terminal BRCT domain and the interaction stimulates the DNA synthesis activity
      of pol lambda. Taken together, these data strongly support that pol lambda
      functions in DNA polymerization events during NHEJ.

PMID- 15451443
TI  - Characterization of early endosome antigen 1 in neural tissues.
AB  - The finding that patients and mice bearing autoantibodies directed against early
      endosome antigen 1 (EEA1) develop neurological signs and deficits prompted an
      investigation of EEA1 distribution, localization, and interaction with synaptic
      proteins found in neural tissues. We detected EEA1 in a variety of neural tissues
      and in cells of neural origin where it co-localized with SNAP-25. The interaction
      between EEA1 and SNAP-25 was dependent on the leucine zipper and a newly
      identified methyl-accepting domain of EEA1. The C-terminal zinc-binding FYVE
      finger motif (EEA1(1271-1411)) of EEA1 also interacted with native SNAP-25 but
      only in the presence of 100microM Ca(2+). In contrast, EEA1 did not bind to
      cysteine string protein or synapsin in these binding assays. These results
      suggest that EEA1 is involved in neuronal synaptic vesicle function and axonal
      transport and growth. EEA1 may undergo calcium-dependent conformational changes
      that are required for binding to SNAP-25.

PMID- 15451445
TI  - Antisense peptide nucleic acids in antibacterial drug discovery.

PMID- 15451446
TI  - Adenoviruses as vaccine vectors.
AB  - Adenoviruses have transitioned from tools for gene replacement therapy to bona
      fide vaccine delivery vehicles. They are attractive vaccine vectors as they
      induce both innate and adaptive immune responses in mammalian hosts. Currently,
      adenovirus vectors are being tested as subunit vaccine systems for numerous
      infectious agents ranging from malaria to HIV-1. Additionally, they are being
      explored as vaccines against a multitude of tumor-associated antigens. In this
      review we describe the molecular biology of adenoviruses as well as ways the
      adenovirus vectors can be manipulated to enhance their efficacy as vaccine
      carriers. We describe methods of evaluating immune responses to transgene
      products expressed by adenoviral vectors and discuss data on adenoviral vaccines
      to a selected number of pathogens. Last, we comment on the limitations of using
      human adenoviral vectors and provide alternatives to circumvent these problems.
      This field is growing at an exciting and rapid pace, thus we have limited our
      scope to the use of adenoviral vectors as vaccines against viral pathogens.

PMID- 15451447
TI  - Update on herpesvirus amplicon vectors.

PMID- 15451448
TI  - Immune-enhancing effects of growth hormone-releasing hormone delivered by plasmid
      injection and electroporation.
AB  - Growth hormone-releasing hormone (GHRH) is a hypothalamic hormone with both
      direct and indirect functions in the maintenance of immune status under
      physiological and pathological conditions. In this study, 52 Holstein heifers
      were evaluated for the effects of a plasmid-mediated GHRH treatment on their
      immune function and on the morbidity and mortality of treated animals. In the
      third trimester of pregnancy, 32 heifers received 2.5 mg of a myogenic GHRH
      expressing plasmid by intramuscular injection followed by electroporation, while
      20 heifers were used as controls. No adverse effects were associated with either
      the plasmid delivery or GHRH expression. At 18 days after plasmid administration,
      GHRH-treated animals had increased numbers of CD2(+) alphabeta T-cells (P <
      0.004), CD25(+)CD4(+) cells (P < 0.0007), and CD4(+)CD45R(+) cells (P < 0.016)
      compared to controls. These increases were maintained long term after treatment
      and correlated with plasmid expression. At 300 days post-GHRH therapy,
      CD45R(+)/CD45R0(-) naive lymphocytes were significantly increased in frequency (P
      < 0.05). Natural killer lymphocytes (CD3(-)CD2(+)) were also increased. As a
      consequence of improved health status, body condition scores of treated animals
      improved (3.55 vs. 3.35, P < 0.0001). Hoof pathology was also reduced with
      treatment. The mortality of heifers was decreased (3% vs. 20% in controls, P <
      0.003). Collectively, these results indicate that the myogenic GHRH plasmid can
      be successfully electrotransferred into a 500-kg mammal and expressed for
      prolonged periods of time, ensuring physiological levels of GHRH. The plasmid
      injection followed by electroporation could prove an efficient method for the
      systemic production of therapeutic proteins and may provide a useful means for
      basic research in relevant animal models.

PMID- 15451449
TI  - Inhibition of Staphylococcus aureus gene expression and growth using antisense
      peptide nucleic acids.
AB  - Gene function studies in bacteria lag behind progress in genome sequencing, in
      part because current reverse genetics technology based on genome disruption does
      not allow subtle control of gene expression for all genes in a range of species.
      Essential genes and clustered regions are particularly problematic. Antisense
      technology offers an attractive alternative for microbial genomics.
      Unfortunately, bacteria lack RNAi mechanisms and conventional oligonucleotides
      are not taken up efficiently. However, in Escherichia coli, efficient and gene
      specific antisense knock down is possible using antisense peptide nucleic acids
      (PNAs) attached to carrier peptides (KFFKFFKFFK). Carrier peptides can enter a
      range of microbial species, and in this study we asked whether peptide-PNAs could
      mediate antisense effects in Staphylococcus aureus. Using low micromolar
      concentrations we observed dose- and sequence-dependent inhibition of the
      reporter gene gfp and endogenous gene phoB. Also, antisense peptide-PNAs targeted
      to the essential genes fmhB, gyrA, and hmrB were growth inhibitory. Control
      peptide-PNAs were much less effective, and sequence alterations within the PNA
      and target mRNA sequences reduced or eliminated inhibition. Further development
      is needed to raise the antibacterial potential of PNAs, but the present results
      show that the approach can be used to study gene function and requirement in this
      important pathogen.

PMID- 15451450
TI  - Site-specific integration of functional transgenes into the human genome by
      adeno/AAV hybrid vectors.
AB  - Uncontrolled insertion of gene transfer vectors into the human genome is raising
      significant safety concerns for their clinical use. The wild-type adeno
      associated virus (AAV) can insert its genome at a specific site in human
      chromosome 19 (AAVS1) through the activity of a specific replicase/integrase
      protein (Rep) binding both the AAVS1 and the viral inverted terminal repeats
      (ITRs). AAV-derived vectors, however, do not carry the rep gene and cannot
      maintain site-specific integration properties. We describe a novel hybrid vector
      carrying an integration cassette flanked by AAV ITRs and a tightly regulated,
      drug-inducible Rep expression cassette in the framework of a high-capacity,
      helper-dependent adenoviral (Ad) vector. Rep-dependent integration of ITR-flanked
      cassettes of intact size and function was obtained in human primary cells and
      cell lines in the absence of selection. The majority of integrations were site
      specific and occurred within a 1000-bp region of the AAVS1. Genome-wide
      sequencing of integration junctions indicates that nonspecific integrations
      occurred predominantly in intergenic regions. Site-specific integration was
      obtained also in vivo, in an AAVS1 transgenic mouse model: upon a single tail
      vein administration of a nontoxic dose of Ad/AAV vectors, AAVS1-specific
      integrations were detected and sequenced in DNA obtained from the liver of all
      animals in which Rep expression was induced by drug treatment. Nonrandom
      integration of double-stranded DNA can therefore be obtained ex vivo and in
      vivoby the use of hybrid Ad/AAV vectors, in the absence of toxicity and with
      efficiency compatible with gene therapy applications.

PMID- 15451451
TI  - Efficient transduction of skeletal muscle using vectors based on adeno-associated
      virus serotype 6.
AB  - Vectors based on recombinant adeno-associated viruses (rAAV) have emerged as
      tools of choice for gene transfer to skeletal muscle. rAAV vectors demonstrate
      efficient, safe, and stable transduction. Multiple serotypes of AAV exist, but
      vectors based on serotype 2 (rAAV2) are the most thoroughly characterized and
      frequently employed. Here, we characterize transduction of the skeletal
      musculature using rAAV vectors pseudotyped with serotype 6 capsid proteins
      (rAAV6). We demonstrate that rAAV6 vectors can efficiently transduce the skeletal
      musculature of mice at levels >500-fold higher than is achievable with rAAV2
      vectors and can readily saturate individual muscles following direct injection.
      Further, rAAV6 vectors are capable of transducing the diaphragm and intercostal
      muscles of mice after a simple injection into the intrathoracic cavity and are
      capable of widespread transduction throughout the musculature of mice injected in
      the intraperitoneal space as newborn pups. These results demonstrate that rAAV6
      vectors hold great potential for use in gene delivery protocols targeting the
      skeletal musculature.

PMID- 15451452
TI  - Nucleofection of muscle-derived stem cells and myoblasts with phiC31 integrase:
      stable expression of a full-length-dystrophin fusion gene by human myoblasts.
AB  - Ex vivo gene therapy offers a potential treatment for Duchenne muscular dystrophy
      by transfection of the dystrophin gene into the patient's own myogenic precursor
      cells, followed by transplantation. We used nucleofection to introduce DNA
      plasmids coding for enhanced green fluorescent protein (eGFP) or eGFP-dystrophin
      fusion protein and the phage phiC31 integrase into myogenic cells and to
      integrate these genes into a limited number of sites in the genome. Using a
      plasmid expressing eGFP, we transfected 50% of a mouse muscle-derived stem cell
      line and 60% of normal human myoblasts. Co-nucleofection of a plasmid expressing
      the phiC31 integrase and an eGFP expression plasmid containing an attB sequence
      produced 15 times more frequent stable expression, because of site-specific
      integration of the transgene. Co-nucleofection of the phiC31 integrase plasmid
      and a large plasmid containing the attB sequence and the gene for an eGFP-full
      length dystrophin fusion protein produced fluorescent human myoblasts that were
      able to form more intensely fluorescent myotubes after 1 month of culture. A
      nonviral approach combining nucleofection and the phiC31 integrase may eventually
      permit safe autotransplantation of genetically modified cells to patients.

PMID- 15451453
TI  - Sustained muscle expression of dystrophin from a high-capacity adenoviral vector
      with systemic gene transfer of T cell costimulatory blockade.
AB  - Adenoviral vector (Ad)-mediated gene delivery of normal, full-length dystrophin
      to skeletal muscle provides a promising strategy for the treatment of Duchenne
      muscular dystrophy (DMD). However, cellular and humoral immune responses induced
      by vector gene transfer limit the application of this approach. Blockade of the
      costimulatory interaction between naive T cells and antigen-presenting cells has
      proven to be a successful means to diminish immunity induced by gene transfer. In
      this study we explore the potential of supplementing dystrophin gene delivery to
      dystrophin-deficient Dmd mouse skeletal muscle with systemic gene delivery of
      CTLA4Ig and CD40Ig molecules to effect costimulatory blockade. We found that
      systemic administration of a high-capacity Ad (HC-Ad) vector carrying murine
      CTLA4Ig (AdmCTLA4Ig) either alone or codelivered with an HC-Ad vector carrying
      murine CD40Ig (AdmCD40Ig) provided sustained expression of recombinant full
      length murine dystrophin from an HC-Ad vector carrying the dystrophin cDNA
      (AdmDys). The level of AdmDys vector genomes remained stable in animals cotreated
      with systemic delivery of vectors carrying molecules to block costimulation. In
      addition, muscle CD4(+) and CD8(+) T cell infiltrates and Th1 cytokine production
      by splenocytes were reduced. The production of neutralizing antibody against Ad
      vector was significantly inhibited in mice receiving systemic codelivery of both
      AdmCTLA4Ig and AdmCD40Ig, but not in the mice treated with AdmCTLA4Ig alone. The
      results suggested that coblockade of both CD28/B7 and CD40L/CD40 costimulatory
      pathways is required for effective inhibition of the Ad vector-induced humoral
      immune response in Dmd mice, whereas blockade of CD28/B7 alone by murine CTLA4Ig
      would be sufficient for prolonged dystrophin expression in treated muscle.

PMID- 15451454
TI  - Identification of pretreatment agents to enhance adenovirus infection of bladder
      epithelium.
AB  - Adenovirus has been used widely as a gene transfer vector in the laboratory and
      clinic for the purpose of gene therapy. Conditionally replication-competent
      oncolytic adenoviruses are capable of multiplying up to a thousand old in target
      cells, a property that might prove to be of tremendous potential in the area of
      cancer therapy. Intravesicular therapy of refractory superficial bladder cancer
      employing an oncolytic adenovirus would allow for local administration and
      efficient delivery of virus to bladder tumor. The glycosaminoglycan layer on the
      surface of the bladder urothelium acts as a nonspecific antiadherence barrier and
      may be a significant roadblock to efficient infection of the urothelium by
      adenoviruses. Several laboratories have investigated the potential utility of
      bladder pretreatment with chemical agents to enhance the adenovirus infection of
      bladder urothelium but with limited success. A class of compounds has been
      identified that is effective for pretreatment of urothelium, permitting efficient
      adenoviral infection. In a murine model, pretreatment of the bladder with 0.1%
      dodecyl-beta-D-maltoside (DDM) or sodium dodecyl sulfate (SDS) for 5 min resulted
      in >90% transduction of the urothelial layer within 15 min after exposure to a
      replication-defective adenovirus compared to </=5% transduction in untreated
      bladders. DDM could be coformulated with adenovirus, and complete transduction of
      the urothelium was achieved following retention of the admixture in the bladder
      for 45 min. A similar enhancement of adenoviral infection following pretreatment
      of bladder with DDM and SDS was observed in a rat model. The use of these
      compounds may facilitate the development of adenovirus-based therapy for bladder
      cancer.

PMID- 15451455
TI  - Membrane-permeant, DNA-binding agents alter intracellular trafficking and
      increase the transfection efficiency of complexed plasmid DNA.
AB  - Nuclear delivery of extracellular DNA by nonviral vectors is inhibited by a
      series of cell membrane and compartmental barriers. Certain cationic amphiphiles
      that partition through cellular membranes to bind genomic DNA can enhance nuclear
      delivery of plasmid DNA. Specifically, delivering plasmid DNA complexed to the
      DNA-binding dye Hoechst 33258 produces cellular transfection levels similar to
      those achieved by cationic liposome:DNA complexes (CLDC), with less toxicity.
      Incorporating Hoechst into CLDC or polyethyleneimine:DNA complexes significantly
      increased reporter gene expression, as well as the percentage of cells
      transfected. Hoechst:CLDC significantly improved transfection of nondividing
      cells and efficiently transfected cells in the presence of anionic molecules that
      block cellular uptake of and transfection by CLDC alone. Hoechst:CLDC also
      increased gene expression in mouse tissues following intravenous delivery.
      Delivery of fluorescently labeled plasmid DNA via Hoechst altered its
      intracellular trafficking by both minimizing lysosomal sequestration and
      accelerating delivery into the nucleus. Agents such as Hoechst constitute a novel
      class of nonviral carriers that can confer their membrane-permeant properties on
      complexed DNA, thus redirecting its intracellular trafficking. In addition,
      binding of Hoechst 33258 to specific chromosomal DNA target sequences and its
      ability to modulate transcription may further enhance the expression of delivered
      genes.

PMID- 15451456
TI  - Enhanced hepatocyte-selective in vivo gene expression by stabilized
      galactosylated liposome/plasmid DNA complex using sodium chloride for complex
      formation.
AB  - In this study, we demonstrated that the presence of an essential amount of sodium
      chloride (NaCl) during the formation of cationic liposome/plasmid DNA complexes
      (lipoplexes) stabilizes the lipoplexes according to the surface charge regulation
      (SCR) theory. Fluorescence resonance energy transfer analysis revealed that
      cationic liposomes in an SCR lipoplex (5 and 10 mM NaCl solution in lipoplex)
      increased fusion. Also, aggregation of SCR lipoplexes was significantly delayed
      after exposure to saline (150 mM NaCl) as a model of physiological conditions.
      After intraportal administration, the hepatic transfection activity of
      galactosylated SCR lipoplexes (5 and 10 mM NaCl solution in lipoplex) was
      approximately 10- to 20-fold higher than that of galactosylated conventional
      lipoplexes in mice. The transfection activity in hepatocytes of galactosylated
      SCR lipoplexes was significantly higher than that of conventional lipoplexes, and
      preexposure to competitive asialoglycoprotein-receptor blocker significantly
      reduced the hepatic gene expression, suggesting that hepatocytes are responsible
      for high hepatic transgene expression of the galactosylated SCR lipoplexes.
      Pharmacokinetic studies both in situ and in vivo demonstrated a higher tissue
      binding affinity and a greater expanse of intrahepatic distribution by
      galactosylated SCR lipoplexes. Moreover, enhanced transfection activity of
      galactosylated SCR lipoplexes was observed in HepG2 cells, and investigation of
      confocal microscopic images showed that the release of plasmid DNA in the cell
      was markedly accelerated. These characteristics partly explain the mechanism of
      enhanced in vivo transfection efficacy by galactosylated SCR lipoplexes. Hence,
      information in this study will be valuable for the future use, design, and
      development of ligand-modified lipoplexes for in vivo applications.

PMID- 15451458
TI  - Human-compatible collagen matrix for prolonged and reversible systemic delivery
      of erythropoietin in mice from gene-modified marrow stromal cells.
AB  - Bone marrow stromal cells (MSCs) can be exploited therapeutically in transgenic
      cell therapy approaches. Our aim was to determine if gene-modified MSCs
      sequestered within a clinically approved, bovine type I collagen-based viscous
      bulking material could serve as a retrievable implant for systemic delivery of
      erythropoietin (Epo). To test this hypothesis, we embedded Epo-secreting MSCs in
      viscous collagen (Contigen) and determined the pharmacological effect following
      implantation in normal mice. Primary MSCs from C57Bl/6 mice were retrovirally
      engineered to express murine Epo (mEpo) and 10(7) cells of a clonal population
      secreting 3 U of mEpo/10(6) cells/24 h were implanted subcutaneously in normal
      C57Bl/6 mice with and without viscous collagen. Without matrix support, Hct rose
      to >70% for <25 days and returned to baseline by 60 days. However, in mice
      implanted with viscous collagen-embedded MSCs, the Hct rose to >70% up to 203
      days postimplantation (P < 0.0001). In parallel, plasma Epo concentration was
      significantly increased (P < 0.05) for >145 days. Moreover, surgical removal of
      the viscous collagen organoid 24 days after implantation led to reduction of Hct
      to baseline levels within 14 days. In conclusion, this investigation demonstrates
      that mEpo(+) MSCs embedded in a human-compatible viscous collagen matrix offers a
      potent, durable, and reversible approach for delivery of plasma-soluble
      therapeutic proteins.

PMID- 15451457
TI  - Differences in F36VMpl-based in vivo selection among large animal models.
AB  - Animal models are indispensable tools for understanding physiological and
      pathological processes, as well as for developing new therapies. Ultimately, the
      results of animal experimentation must provide information that can guide the
      development of therapeutic approaches in humans. Significant differences have
      been reported comparing a gene therapy approach between different animal models.
      However, little information exists describing differences among the available
      large animal models. Here we evaluated, in the hemopoietic cells of baboons, a
      system of selection that has previously demonstrated activity in mice, in dogs,
      and in human cells ex vivo. This system employs a derivative of the murine
      thrombopoietin receptor (F36Vmpl), which is conditionally activated in the
      presence of a small-molecule drug called a chemical inducer of dimerization
      (CID). Whereas cultured mouse, human, and, to a lesser extent, dog hemopoietic
      cells all proliferate in response to the F36Vmpl signal, we observed only a minor
      and variable response to the F36Vmpl signal in the cultured cells of baboons.
      Similarly, we have noted significant rises in the frequency of transduced
      hemopoietic cells in mice and in dogs upon CID administration in vivo; however,
      here we show that responses to CID administration in three baboons were modest
      and variable. These findings have general implications for the evaluation and
      development of new strategies for gene therapy.

PMID- 15451459
TI  - Impact of E1a modifications on tumor-selective adenoviral replication and
      toxicity.
AB  - Replicating adenoviral vectors are capable of multiplying up to a thousandfold in
      the target cell, a property that might prove to be of tremendous potential for
      cancer therapy. However, restricting viral replication and toxicity to cancer
      cells is essential to optimize safety. It has been proposed that modifications of
      the E1a protein that impair binding to Rb or p300 will prevent S-phase induction
      in normal cells, resulting in selective viral replication in tumor cells.
      However, it remains uncertain which of the several possible E1a modifications
      would be most effective at protecting normal cells without compromising the
      oncolytic effect of the vector. In this study, we have expressed several E1a
      deletion mutants at high levels using the CMV promoter and tested them for their
      ability to facilitate S-phase induction, viral replication, and cytotoxicity in
      both normal and cancer cells. Deletion of the Rb-binding domain within E1a only
      slightly decreased the ability of the virus to induce S phase in growth-arrested
      cells. The effect of this deletion on viral replication and cytotoxicity was
      variable. There was reduced cytotoxicity in normal bronchial epithelial cells;
      however, in some normal cell types there was equal viral replication and
      cytotoxicity compared with wild type. Deletions in both the N-terminus and the Rb
      binding domain were required to block S-phase induction effectively in growth
      arrested normal cells; in addition, this virus demonstrated reduced viral
      replication and cytotoxicity in normal cells. An equally favorable replication
      and cytotoxicity profile was induced by a virus expressing E1a that is incapable
      of binding to the transcriptional adapter motif (TRAM) of p300. All viruses were
      equally cytotoxic to cancer cells compared with wild-type virus. In conclusion,
      deletion of the Rb-binding site alone within E1a may not be the most efficacious
      means of targeting viral replication and toxicity. However, deletion within the N
      terminus in conjunction with a deletion within the Rb-binding domain, or deletion
      of the p300-TRAM binding domain, induces a more favorable cytotoxicity profile.

PMID- 15451460
TI  - The human SCGB2A2 (mammaglobin-1) promoter/enhancer in a helper-dependent
      adenovirus vector directs high levels of transgene expression in mammary
      carcinoma cells but not in normal nonmammary cells.
AB  - Expression of secretoglobin family 2A member 2 (SCGB2A2, also known as
      mammaglobin-1) has been detected in a high percentage of primary and metastatic
      breast tumors, to a lesser extent in normal breast, but not in other normal
      tissues. Plasmid transfection studies in our lab and others, however, were unable
      to identify the genetic elements regulating this specificity. Here we demonstrate
      that a 25-kb DNA fragment derived from the human SCGB2A2 gene upstream of the
      protein coding sequence was highly active and preferentially expressed in breast
      cancer cells when introduced via a helper-dependent adenoviral (HDAd) vector.
      HDAd delivery was selected for its high cloning capacity, its high efficiency of
      gene transfer, and the absence of cis-acting viral sequences that can potentially
      interfere with specificity of the inserted promoters. A series of vectors with
      deletions in the 25-kb fragment was constructed to identify important regulatory
      regions of the SCGB2A2 promoter. We have determined that elements controlling the
      specificity of expression reside within the first 345 bp upstream of the coding
      sequence. In addition, we identified a strong enhancer several kilobases upstream
      of this minimal promoter. We suggest that the SCGB2A2 promoter/enhancer should be
      particularly advantageous for gene therapy protocols involving oncolytic viruses
      or toxic gene transfer via adenovectors to mammary tumors.

PMID- 15451461
TI  - Side-by-side comparison of lentivirally transduced and mRNA-electroporated
      dendritic cells: implications for cancer immunotherapy protocols.
AB  - The use of tumor antigen-loaded dendritic cells (DC) is one of the most promising
      approaches to inducing a tumor-specific immune response. We compared
      electroporation of mRNA to lentiviral transduction for the delivery of tumor
      antigens to human monocyte-derived and murine bone marrow-derived DC. Both
      lentiviral transduction and mRNA electroporation induced eGFP expression in on
      average 81% of human DC. For murine DC, eGFP mRNA electroporation (62%) proved to
      be more efficient than lentiviral transduction (47%). When we used tNGFR as a
      transgene we observed lentiviral pseudotransduction that overestimated lentiviral
      efficiency. Neither gene transfer method had an adverse effect on viability,
      phenotype, or allostimulatory capacity of either human or murine DC. Yet, the
      mRNA-electroporated DC showed a reduced production of IL-12p70 compared to their
      lentivirally transduced and unmodified counterparts. Human Ii80MAGE-A3-modified
      DC and murine Ii80tOVA-modified DC were able to present antigenic epitopes in the
      context of MHC class I and class II. Both types of modified murine DC were able
      to induce OVA-specific cytotoxic T cells in vivo; however, the mRNA
      electroporated DC were less potent. Our data indicate that this may be related to
      their impaired IL-12 production.

PMID- 15451462
TI  - Factors influencing the production of recombinant SV40 vectors.
AB  - Most gene therapy approaches employ viral vectors for gene delivery. Ideally,
      these vectors should be produced at high titer and purity with well-established
      protocols. Standardized methods to measure the quality of the vectors produced
      are imperative, as are techniques that allow reproducible quantitation of viral
      titer. We devised a series of protocols that achieve high-titer production and
      reproducible purification and provide for quality control and titering of
      recombinant simian virus 40 vectors (rSV40s). rSV40s are good candidate vehicles
      for gene transfer: they are easily modified to be nonreplicative and they are
      nonimmunogenic. Further, they infect a wide variety of cells and allow long-term
      transgene expression. We report here these protocols to produce rSV40 vectors in
      high yields, describe their purification, and characterize viral stocks using
      quality control techniques that monitor the presence of wild-type SV40 revertants
      and defective interfering particles. Several methods for reproducible titration
      of rSV40 viruses have been compared. We believe that these techniques can be
      widely applied to obtain high concentrations of high-quality rSV40 viruses
      reproducibly.

PMID- 15451463
TI  - Physical and infectious titers of helper-dependent adenoviral vectors: a method
      of direct comparison to the adenovirus reference material.
AB  - Accurate measurements of the physical and infectious titers of adenoviral vectors
      are crucial for evaluating preclinical studies and for the safety and efficacy of
      clinical studies. Unfortunately, there are no standardized methods of
      measurement, consequently variable and unreliable values are the result.
      Furthermore, infectious titers of helper-dependent adenoviral vectors (HDAd) are
      difficult to measure because traditional cytopathic effect assays cannot be
      employed, thus hindering their potential clinical application. In response to
      this problem, a fully characterized Adenovirus Reference Material (ARM) has been
      developed to be used as a reference standard for clinical grade adenoviral
      vectors. However, no specific protocols for this purpose have been provided. To
      fulfill this important need, we have developed a simple assay involving co
      infection of 293 cells with the adenoviral vector and the ARM to permit direct
      comparisons of their physical and infectious titers. We demonstrate, using a
      HDAd, that this co-infection assay is reliable, sensitive, and reproducible.
      Importantly, this assay is inherently unaffected by variables that plague other
      methods of determining vector titers. This assay is applicable to all human
      serotype 5 adenoviral vectors and will permit reliable comparisons within and
      between studies as well as meet an important prerequisite for clinical studies.

PMID- 15451464
TI  - Phase I study of autologous tumor vaccines transduced with the GM-CSF gene in
      four patients with stage IV renal cell cancer in Japan: clinical and
      immunological findings.
AB  - We produced lethally irradiated retrovirally GM-CSF-transduced autologous renal
      tumor cell vaccines (GVAX) from six Japanese patients with stage IV renal cell
      cancer (RCC). Four patients received GVAX ranging from 1.4 x 10(8) to 3.7 x 10(8)
      cells on 6-17 occasions. Throughout a total of 48 vaccinations, there were no
      severe adverse events. After vaccination, DTH skin tests became positive to
      autologous RCC (auto-RCC) in all patients. The vaccination sites showed
      significant infiltration by CD4(+) T cells, eosinophils, and HLA-DR-positive
      cells. The kinetic analyses of cellular immune responses using peripheral blood
      lymphocytes revealed an enhanced proliferative response against auto-RCC in four
      patients, and cytotoxicity against auto-RCC was augmented in three patients. T
      cell receptor beta-chain analysis revealed oligoclonal expansion of T cells in
      the peripheral blood, skin biopsy specimens from DTH sites, and tumors. Western
      blot analysis demonstrated the induction of a humoral immune response against
      auto-RCC. Two of the four patients are currently alive 58 and 40 months after the
      initial vaccination with low-dose interleukin-2. Our results suggest that GVAX
      substantially enhanced the antitumor cellular and humoral immune responses, which
      might have contributed to the relatively long survival times of our patients in
      the present study.

PMID- 15451465
TI  - Interpreting diagnostic studies in SARS--defining the reference.

PMID- 15451466
TI  - The role of very late antigen-1 in immune-mediated inflammation.
AB  - The alpha1beta1 integrin, also known as "very late antigen" (VLA)-1, is normally
      expressed on mesenchymal cells, some epithelial cells, activated T cells, and
      macrophages, and interacts, via the I-domain of the extracellular domain of the
      alpha1 subunit, with collagen molecules in the extracellular matrix (ECM). By
      "outside-in" transmembranal signaling to the interior of the cell, it mediates
      adhesion, migration, proliferation, remodeling of the ECM, and cytokine secretion
      by endothelial cells, mesangial cells, fibroblasts, and immunocytes. Importantly,
      its expressions and functions are enhanced by inflammatory cytokines including
      interferon (IFN)gamma and tumor necrosis factor (TNF)alpha, thus augmenting
      angiogenesis and fibrosis linked, in particular, to inflammation. Moreover,
      within the immune system, VLA-1 marks effector memory CD4+ and CD8+ T cells that
      are retained in extralymphatic tissues by interactions of the integrin with
      collagen and produce high levels of IFNgamma. Thus, immune-mediated inflammation
      in vivo is inhibited by blockade of the VLA-1-collagen interaction in
      experimental animal models of arthritis, colitis, nephritis, and graft versus
      host disease (GVHD), suggesting that inhibiting the interaction of the alpha1 I
      domain with its ligands or modulating "outside-in" signaling by VLA-1 would be a
      useful approach in the human diseases simulated by these experimental models.

PMID- 15451467
TI  - Mycobacterial granulomas: keys to a long-lasting host-pathogen relationship.
AB  - Chronic infection with mycobacteria is controlled by the formation of granulomas.
      The failure of granuloma maintenance results in reactivation of disease.
      Macrophages are the dominant cell type in granulomas, but CD4+ T cells are the
      master organizers of granuloma structure and function. Recent work points to an
      unrecognized role for nonspecific T cells in maintaining granuloma function in
      the chronic phase of infection. In addition, it has become clear that
      mycobacteria and host T cells collaborate in formation of granulomas. Further
      understanding of how nonspecific T cells contribute to granuloma formation, as
      well as how bacteria and T cells maintain a harmonious relationship over the life
      of the host, will facilitate the development of new strategies to treat
      mycobacterial disease.

PMID- 15451468
TI  - Immunosuppressants, infection, and inflammation.

PMID- 15451469
TI  - Differential expression of interferon-gamma and interferon-gamma-inducing
      cytokines in Thai patients with scrub typhus or leptospirosis.
AB  - Interferon (IFN)-gamma plays an important role in the induction of a type 1
      immune response against intracellular pathogens. We compared the plasma levels of
      IFN-gamma and IFN-gamma-inducing cytokines in adult Thai patients with scrub
      typhus, caused by the obligate intracellular bacterium Orientia tsutsugamushi,
      and leptospirosis, caused by extracellular Leptospira interrogans. IFN-gamma,
      interleukin (IL)-18, and IL-15 levels were elevated only in patients with scrub
      typhus, whereas IL-12p40 and tumor necrosis factor-alpha concentrations were
      elevated in both patient groups, although more so in scrub typhus. These data
      suggest a role for a cell-mediated immune response in host defense against O.
      tsutsugamushi.

PMID- 15451470
TI  - Detection of antibodies against SARS-CoV in serum from SARS-infected donors with
      ELISA and Western blot.
AB  - Recombinant fragments of S proteins from the Severe Acute Respiratory Syndrome
      (SARS) coronavirus (SARA-CoV) were generated and used in a Western blot (WB)
      assay that was compared to a commercial SARS ELISA method. In 85% of confirmed
      SARS cases (n = 20), the S2 recombinant fragment based WB was positive and this
      was comparable to the commercial ELISA using heat killed SARS-CoV. WB using the
      other four recombinant fragments in confirmed SARS cases generated lower rates of
      detection (S1--75%, S1-N--25%, S1-C--55%). Evaluation of sera from healthy
      controls (n = 60) resulted in two weakly positive ELISA results with the
      remainder being negative while the S2 protein WB demonstrated three positive
      results from the 20 controls with a history of SARS contact and no positive
      results in 40 noncontact controls. A discrepancy between the ELISA and S2 WB
      arose when evaluating per-2003 sera from individuals (n = 10) with SARS-like
      symptoms (ELISA--100% positive, S2 WB--30% positive). These data suggest that the
      S2 WB assay may be particularly useful in ELISA-negative SARS cases and in some
      ELISA-positive non-SARS cases.

PMID- 15451471
TI  - Detecting specific cytotoxic T lymphocytes against SARS-coronavirus with DimerX
      HLA-A2:Ig fusion protein.
AB  - To assess specific cytotoxic T lymphocytes (CTLs) against Severe acute
      respiratory syndrome (SARS)-coronavirus, a modified DimerX flow cytometry assay
      was performed with peripheral blood mononuclear cell (PBMC) from HLA-A2+ SARS
      recovered donors at different time points post disease. CD8+DimerX-S1203+ CTLs
      were detected in the PBMC from these donors up to 3 months after recovery. The
      percentages of CD8+DimerX-S1203+ cells paralleled the numbers of interferon-gamma
      positive spots in an ELISPOT assay using the same antigenic peptide. In
      conclusion, DimerX-based flow cytometry staining may prove to be a real-time
      method to screen for CTL directed at epitopes from a newly identified virus.

PMID- 15451472
TI  - T cell vaccination in multiple sclerosis relapsing-remitting nonresponders
      patients.
AB  - Myelin autoreactive T cells are involved in the pathogenesis of multiple
      sclerosis (MS) and lead to propagation of the disease. We evaluated the efficacy
      of T cell vaccination (TCV) therapy for patients with aggressive relapsing
      remitting MS who failed to respond to immunomodulatory treatments. Twenty
      nonresponders relapsing-remitting MS patients were immunized with autologous
      attenuated T cell lines after activation with synthetic myelin basic protein
      (MBP) and myelin oligodendrocyte glycoprotein (MOG) encephalitogenic peptides.
      Each patient received three vaccinations in 6- to 8-week intervals. Annual
      relapse rate decreased from 2.6 to 1.1, P = 0.026. Neurological disability
      stabilized as compared with the 2- and 1-year pretreatment progression rates.
      Significant reduction in the number and volume of active lesions, as well as
      reduction in T2 lesion burden, was demonstrated by quantitative MRI analysis. No
      serious adverse events were observed. Our findings suggest that TCV has
      beneficial clinical effects in MS patients who, in spite of immunomodulatory
      treatments, continue to deteriorate. TCV could serve as a potential alternative
      therapy for this subgroup of nonresponders patients.

PMID- 15451473
TI  - A new CD21low B cell population in the peripheral blood of patients with SLE.
AB  - A hallmark of systemic lupus erythematosus (SLE) is the production of
      autoantibodies. Recent reports suggest an abnormal peripheral blood B cell
      homeostasis in SLE patients without being conclusive. We analyzed by four color
      flow-cytometry peripheral blood B cell subpopulations of SLE patients, healthy
      donors, and patients with other systemic autoimmune diseases. IgM memory but not
      switched memory B cells of SLE patients were significantly decreased compared to
      healthy donors, whereas transitional B cells, characterized by
      CD19+IgMhiIgD+CD24hiCD38hi, were significantly expanded in SLE patients but also
      found in other autoimmune disorders. The population of plasmablasts
      (CD19loCD21loCD27++CD38++) was increased in active disease. Most interestingly, B
      cells in autoimmune disorders contain a so far uncharacterized subpopulation with
      an activated phenotype (CD19hiCD21loCD38loCD86int). None of the identified
      subpopulations was associated with current or previous therapy and therefore may
      represent different aspects of the disturbed B cell homeostasis in patients with
      SLE.

PMID- 15451474
TI  - Regulatory CD4+CD25+ T lymphocytes in peripheral blood from patients with atopic
      asthma.
AB  - The aim of this study was to analyze whether regulatory CD4+CD25+ T lymphocytes
      exist and function normally in patients with atopic asthma. Our data showed that
      a significant increase in CD4+CD25+ cell numbers was seen in atopic asthmatics
      during acute exacerbation, but not in those stable asthmatics, atopic
      nonasthmatics, and normal subjects. The mean inhibition values of the
      proliferation response of CD4+CD25- cells by CD4+CD25+ cells from normal controls
      and asthmatics were almost the same. There was no difference in inhibitory
      effects on both Th1 and Th2 cytokine production of CD4+CD25- cells by CD4+CD25+
      cells in the two groups. These data demonstrated that although CD4+CD25+ cells
      increase in atopic asthma during exacerbation, these regulatory T cells appear to
      function normally with regard to suppression of T-cell proliferation as well as
      Th1-Th2 cytokine production.

PMID- 15451475
TI  - T cell receptor gene usage of BP180-specific T lymphocytes from patients with
      bullous pemphigoid and pemphigoid gestationis.
AB  - BP180 is the autoantigen of different immunobullous diseases, including bullous
      pemphigoid (BP) and pemphigoid gestationis (PG). Previously, we demonstrated that
      the NC16A domain of this autoantigen harbors key epitopes of autoantibodies and T
      cells, indicating that it plays an essential role in the pathogenesis of
      diseases. Moreover, NC16A-specific T cell clones derived from these patients were
      shown to express a CD4+ memory T cell phenotype and secrete cytokines that may
      promote autoantibody production. In this study, we further characterize the
      properties of these T cells by analyzing their epitope specificity and T cell
      receptor (TCR) gene usage. We discovered that 83% of T cell clones obtained from
      BP patients preferentially express TCRBV13, while clones derived from a PG
      patient express the TCRBV3 gene. However, no preferential TCRBJ gene usage was
      identified. In conclusion, our results provide an advanced understanding of the
      characteristics of autoimmune T cells in immunobullous diseases.

PMID- 15451476
TI  - Experimental autoimmune thyroiditis in nonobese diabetic mice lacking interferon
      regulatory factor-1.
AB  - Interferon regulatory factor-1 (IRF-1) is pivotal in the regulation of interferon
      (IFN)-mediated immune reactions, and studies suggest that IRF-1 is involved in
      the development of autoimmune diseases. IRF-1+/+, +/-, and -/- nonobese diabetic
      (NOD) mice were immunized with mouse thyroglobulin (mTg) to determine whether IRF
      1 is required in experimental autoimmune thyroiditis (EAT), a murine model for
      Hashimoto's thyroiditis (HT). IRF-1-deficient mice developed EAT and anti-mTg
      antibodies comparable to IRF-1+/+ and +/- mice. Whereas both CD4+ and CD8+ T
      cells were found in thyroids of IRF-1+/+ mice, the latter was not in IRF-1-/-
      mice. Major histocompatibility complex class II antigen was comparably expressed
      in thyroids of IRF-1+/+ and -/- mice. Lack of IRF-1 resulted in decreased CD8+ T
      cell number in the spleen and reduced IFNgamma production by splenocytes. Our
      results suggest that IRF-1 is not pivotal in EAT in NOD mice.

PMID- 15451477
TI  - Human mAChR antibodies from Sjogren syndrome sera increase cerebral nitric oxide
      synthase activity and nitric oxide synthase mRNA level.
AB  - We demonstrated the presence of circulating antibodies from Sjogren syndrome (SS)
      patients enable to interact with rat cerebral frontal cortex by activating
      muscarinic acetylcholine receptors (mAChRs). IgG from SS and IgG from normal
      subjects were studied by flow cytometry, enzyme immunoassay (ELISA), and
      radioligand binding assays. By flow cytometric and ELISA procedures, it was shown
      that IgG from SS patients reacted to cerebral frontal cortex cell surface. SS IgG
      was able to interact with mAChR by inhibiting 3H-QNB binding to its specific
      receptor. Besides, SS IgG displayed an agonistic-like activity associated to
      specific M1 and M3 mAChR activation, increasing nitric oxide synthase (NOS)
      isoform activities. Neuronal (n) and endothelial (e) NOS-mRNA gene expression of
      rat frontal cortex is induced by SS IgG. This article supports the participation
      of humoral immune alterations in SS, resulting in central parasympathetic
      functional deregulation. These antibodies alter mAChR activation, NOS activity,
      and eNOS and nNOS gene expression.

PMID- 15451478
TI  - Human multiple myeloma cells express peroxisome proliferator-activated receptor
      gamma and undergo apoptosis upon exposure to PPARgamma ligands.
AB  - Multiple myeloma is essentially an incurable malignancy and it is therefore of
      great interest to develop new therapeutic approaches. We previously reported that
      human B cell-lymphomas express the nuclear receptor peroxisome proliferator
      activated receptor gamma (PPARgamma) and are killed by PPARgamma ligands. Herein,
      we investigate the therapeutic potential of PPARgamma ligands for multiple
      myeloma. The human multiple myeloma cell lines ANBL6 and 8226 express PPARgamma
      mRNA and protein. The PPARgamma ligands, 15-deoxy-Delta12,14-prostaglandin J2
      (15d-PGJ2) and ciglitazone, induced multiple myeloma cell apoptosis as determined
      by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling
      (TUNEL) assay, loss of mitochondrial membrane potential, and caspase activation.
      Importantly, the ability of PPARgamma ligands to kill both multiple myeloma cell
      lines was not abrogated by Interleukin-6 (IL-6), a multiple myeloma growth
      survival factor. Finally, the RXR ligand 9-cis retinoic acid (9-cis RA) in
      combination with PPARgamma ligands greatly enhanced multiple myeloma cell
      killing. These new findings support that PPARgamma ligands may represent a novel
      therapy for multiple myeloma.

PMID- 15451479
TI  - The clinical and biological overlap between Nijmegen Breakage Syndrome and
      Fanconi anemia.
AB  - Fanconi anemia (FA), an autosomal recessive chromosomal instability syndrome, is
      characterized clinically by developmental abnormalities, growth retardation,
      progressive bone marrow failure, pancytopenia, and pronounced cancer
      predisposition. Nijmegen Breakage Syndrome (NBS) is a related disorder that
      shares overlapping clinical features, principally, developmental delay,
      microcephaly, and cancer predisposition. The diagnosis has relied on chromosomal
      instability following exposure to DNA cross-linking agents in FA and to ionizing
      radiation (IR) in NBS. We describe two patients who clinically had FA, but showed
      sensitivity to both DNA cross-linking agents and ionizing radiation, and who were
      found to have a rare mutation in the NBS gene. The importance of genetic
      diagnosis with respect to treatment and prognosis is discussed.

PMID- 15451480
TI  - Avian influenza should be ruffling our feathers.

PMID- 15451481
TI  - Lyme borreliosis: perspective of a scientist-patient.

PMID- 15451482
TI  - Human monkeypox.

PMID- 15451484
TI  - Injecting reason.

PMID- 15451485
TI  - The International Health Regulations and beyond.

PMID- 15451486
TI  - Fluoroquinolone-resistant Shigella dysenteriae type 1 in northeastern Bangladesh.

PMID- 15451487
TI  - Citation analysis for The Lancet Infectious Diseases.

PMID- 15451489
TI  - How antibiotics can make us sick: the less obvious adverse effects of
      antimicrobial chemotherapy.
AB  - Antimicrobial agents are associated with side-effects, which are usually
      tolerated because the benefits of treatment outweigh the toxic effects.
      Clinicians know about these side-effects but are less likely to understand
      additional adverse events, such as the overgrowth of resistant microorganisms.
      Overgrowth can itself precipitate a secondary infection, which can be more
      difficult to treat. Resistant organisms then spread to other patients and the
      environment, and contribute to increasing antimicrobial resistance worldwide.
      Organisms exposed to antibiotics undergo molecular changes that might enhance
      virulence. Enhanced pathogenicity would affect patients, particularly if the
      organism is also multiply resistant. Clinicians have a responsibility to select
      the correct antibiotic as soon as they have diagnosed infection, but an absence
      of microbiological understanding and ignorance of the potential environmental
      effects have contributed to inappropriate prescribing. The less obvious results
      of antimicrobial consumption probably go unrecognised in routine clinical care.

PMID- 15451490
TI  - Procalcitonin as an early marker of infection in neonates and children.
AB  - A child or neonate presenting with fever is a common medical problem. To
      differentiate between those with a severe bacterial infection and those with a
      localised bacterial or a viral infection can be a challenge. This review provides
      an overview of neonatal and paediatric studies that assess the use of
      procalcitonin as an early marker of bacterial infection. Procalcitonin is an
      excellent marker for severe, invasive bacterial infection in children. However,
      the use of procalcitonin in the diagnosis of neonatal bacterial infection is
      complicated, but if correctly used procalcitonin results in a higher specificity
      than C-reactive protein. In addition, procalcitonin has been shown to correlate
      with severity of disease (urinary tract infections and sepsis), and can therefore
      be used as a prognostic marker. Procalcitonin is therefore a useful additional
      tool for the diagnosis of bacterial disease in neonates and children.

PMID- 15451491
TI  - Pathogenesis of urinary tract infections with normal female anatomy.
AB  - Recurrent urinary tract infections (UTIs) are common among girls and young women
      who are healthy and have anatomically normal urinary tracts. These infections are
      a main source of morbidity and health-care costs in this population. The
      interaction between specific infecting bacteria and urinary tract epithelium
      characteristics underlies the pathogenesis of this disease. Several pathogen
      related factors predispose people to recurrent UTI, including periurethral
      bacterial colonisation and Escherichia coli virulence. Host behavioural risk
      factors include voiding dysfunction, high intercourse frequency, and oral
      contraceptive and spermicide use. The role of vesicoureteral reflux in recurrent
      childhood UTI is probably overestimated in the medical literature and is
      important only in a small group of children with high-grade reflux. Family
      pedigree analysis suggests a familial genetic predisposition for UTI among young
      females. Animal models show the multigenic nature of recurrent UTI. Putative
      candidate genes for the disease include ABH blood groups, interleukin-8 receptor
      (CXCR1), the human leucocyte antigen locus, toll-like receptors, tumour necrosis
      factor, and Tamm-Horsfall protein.

PMID- 15451492
TI  - Could disease-modifying HIV vaccines cause population-level perversity?
AB  - Most current candidate HIV vaccines seem to produce little protection against
      infection, but reduce viral load and slow the decline in CD4 lymphocyte numbers.
      Such disease-modifying vaccines could potentially provide important population
      level benefits by reducing transmission, but could possibly also increase
      transmission. We address the following question: could disease-modifying HIV
      vaccines cause population-level perversity (ie, increase epidemic severity)? By
      analysing a mathematical model and defining a new quantity-the fitness ratio-we
      show that disease-modifying vaccines that provide only a low degree of protection
      against infection and/or generate high fitness ratios will have a high
      probability of making the epidemic worse. However, we show that if disease
      modifying vaccines cause a 1.5 log(10) reduction in viral load (or greater) then
      perversity cannot occur (assuming risk behaviour does not increase). Finally, we
      determine threshold surfaces for risk behaviour change that determine the
      boundary between beneficial and perverse outcomes; the threshold surfaces are
      determined by the fitness ratio, the proportion of the population that are
      "successfully vaccinated", and the degree of change of risk behaviour in
      unvaccinated infected individuals. We discuss the implications of our results for
      designing optimal vaccination control strategies.

PMID- 15451493
TI  - Self-testing for HIV: a new option for HIV prevention?
AB  - Self-testing has the potential to be an innovative component to community-wide
      HIV-prevention strategies. This testing method could serve populations who do not
      have access to standard voluntary counselling and testing services or because of
      privacy concerns, stigma, transport costs, or other barriers do not use facility
      based, standard HIV testing. This paper reviews recent research on the
      acceptability, feasibility, and cost of rapid testing and home-specimen
      collection for HIV, and suggests that self-testing may be another important
      strategy for diagnosing HIV infection. Several research questions are posed that
      should be answered before self-testing is realised.

PMID- 15451494
TI  - Group A streptococcal infection after bovine bone fragment injury.

PMID- 15451495
TI  - Muck spreading.

PMID- 15451496
TI  - The challenge of antibiotic resistant bacterial pathogens: the medical need, the
      market and prospects for new antimicrobial agents.

PMID- 15451497
TI  - Microbiology and drug resistance mechanisms of fully resistant pathogens.
AB  - The acquisition of vancomycin resistance by Gram-positive bacteria and carbapenem
      resistance by Gram-negative bacteria has rendered some hospital-acquired
      pathogens impossible to treat. The resistance mechanisms employed are
      sophisticated and very difficult to overcome. Unless alternative treatment
      regimes are initiated soon, our inability to treat totally resistant bacteria
      will halt other developments in medicine. In the community, Gram-positive
      bacteria responsible for pneumonia could become totally resistant leading to
      increased mortality from this common infection, which would have a more immediate
      impact on our current lifestyles.

PMID- 15451498
TI  - Antibacterial research and development in the 21(st) Century--an industry
      perspective of the challenges.
AB  - The continued evolution of resistance to antibiotics has led to wide ranging
      consultation at National and International levels as to how to address this
      issue. In addition to attempting to limit the spread of resistance there is
      growing consensus that a cornerstone requirement is the development of new
      antibiotics to help redress the balance of resistance versus available
      antibiotics. The availability of new technologies such as genomics has opened up
      new approaches for antibacterial research. It would appear that from an industry
      perspective, the research and development of antibiotics should be an attractive
      option. However, this is not the current perception at the majority of large
      pharmaceutical companies. In addition, the perceived failure of new technologies
      to create another golden age of new antibacterial classes has led many companies
      to prioritise other areas of research and, in some cases, to exit antibacterial
      research. In response, a plethora of small biotech companies have emerged with an
      interest in antibacterial discovery and large pharmaceutical companies may look
      to these as a source of development candidates although, to date, these have
      contributed a very low number of truly novel antibiotic lead compounds. As a
      reaction to these changes several initiatives are ongoing to examine ways to
      incentivise antibacterial research and development and ensure a healthy pipeline
      of compounds in the 21st Century.

PMID- 15451499
TI  - The impact of transcriptome and proteome analyses on antibiotic drug discovery.
AB  - Recent scientific publications demonstrate the increasing interest in measurement
      of genome-wide gene expression on transcript and protein level in response to
      treatment with antibacterial agents. Nevertheless, the number of large bacterial
      transcriptome and proteome datasets available so far is limited, although a high
      number and diversity of antibiotic-triggered expression profiles aid to optimally
      exploit these technologies. The first published examples substantiate the need to
      establish these so-called reference compendia of bacterial expression profiles,
      to discover the molecular mechanism-of-action of uncharacterized bioactive
      substances. In addition, such compendia open up ways for novel cell-based drug
      screening approaches.

PMID- 15451500
TI  - Prospects for new antitubercular drugs.
AB  - The inexorable rise in cases of tuberculosis worldwide, fuelled by the HIV
      epidemic, highlights the need for new drugs and particularly those that can
      shorten the duration of treatment. Clinical trials of existing broad-spectrum
      agents such as the fluoroquinolone moxifloxacin are proceeding, on the basis of
      efficacy in models of infection and preliminary clinical data. These may provide
      a stopgap, but the real breakthrough will come when novel agents with potent
      sterilising activity are discovered. Few such novel pre-clinical drug candidates
      exist and therefore considerable effort is being exerted to employ new tools to
      identify drug targets essential for survival of Mycobacterium tuberculosis.

PMID- 15451501
TI  - Taking inventory: antibacterial agents currently at or beyond phase 1.
AB  - At least 18 antibacterial agents are currently undergoing clinical trials for the
      treatment of infections caused by susceptible and resistant bacteria. The beta
      lactam class includes new parenteral carbapenems and cephalosporins with varying
      spectra of activities. The glycopeptides are antibiotics with in vitro activity
      primarily against Gram-positive bacteria, including multi-resistant strains.
      Three quinolones are being investigated for use against a variety of Gram
      positive and respiratory Gram-negative organisms. Several other classes of
      antibacterial agents currently in clinical trials are represented by a
      glycolipodepsipeptide, a dihydrofolate reductase inhibitor, an oxazolidinone, two
      peptide antibiotics, a glycylcycline, and a peptide deformylase inhibitor, a
      member of a new antibacterial class.

PMID- 15451502
TI  - Staphylococci in colonization and disease: prospective targets for drugs and
      vaccines.
AB  - Pathogenic staphylococci are now regarded in the scientific community as
      antibiotic resistant 'superbugs' because they have an amazing capacity to acquire
      resistance traits. Surprisingly, antibiotic development has decelerated.
      Promising targets for drug development are enzymes involved in the biosynthesis
      of cell envelope structures such as peptidoglycan, teichoic acids, membrane
      lipids, or cell wall associated adhesins. Compounds that inactivate or neutralize
      the most aggressive toxins such as the superantigens and the pore forming toxins
      have also been considered. In the past decade, global regulatory systems have
      been studied that contribute to virulence and might be candidates for target
      development. Targets that are particularly promising include all enzymatic
      reactions that are unique to bacteria and that are involved in central
      metabolism, such as methionine-tRNA(fMet) formyltransferase or the peptide
      deformylase, which have been successfully used for designing new inhibitors.
      There are also several known antibiotics that have roused new interest especially
      if they are active against multi-resistant staphylococci. Various cell wall
      components are promising candidates for active and passive immunization
      strategies such as capsule, slime, teichoic acids or cell wall bound adhesins.
      Several new targets for drugs or vaccines will arise from the functional analysis
      of the staphylococcal genomes that contain many hitherto unknown targets.

PMID- 15451503
TI  - Beyond the genome: from genomics to systems biology.

PMID- 15451504
TI  - Metagenomics--the key to the uncultured microbes.
AB  - It is widely accepted that up to 99.8% of the microbes present in many
      environments are not readily culturable. 'Metagenome technology' tries to
      overcome this bottleneck by developing and using culture-independent approaches.
      From the outset, metagenome-based approaches have led to the accumulation of an
      increasing number of DNA sequences, but until this time the sequences retrieved
      have been those of uncultured microbes. These genomic sequences are currently
      exploited for novel biotechnological and pharmaceutical applications and to
      increase our knowledge on microbial ecology and physiology of these microbes.
      Using the metagenome sequences to fully understand how complex microbial
      communities function and how microbes interact within these niches represents a
      major challenge for microbiologists today.

PMID- 15451505
TI  - From genomics to post-genomics in Aspergillus.
AB  - Genome sequence data has recently become available for certain Aspergillus
      species. We consider the transition from genomics to a post-genomic era in
      Aspergillus, describing resources and methodologies available to underpin
      research efforts. Advances in our understanding of the fundamental biology of the
      Aspergilli, together with applications within the biotechnology and medical
      fields, are anticipated.

PMID- 15451506
TI  - Protein interaction networks in bacteria.
AB  - The complement of expressed cellular proteins - the proteome - is organized into
      functional, structured networks of protein interactions that mediate assembly of
      molecular machines and dynamic cellular pathways. Recent studies reveal the
      biological roles of protein interactions in bacteriophage T7 and Helicobacter
      pylori, and new methods allow to compare and to predict interaction networks in
      other species. Smaller scale networks provide biological insights into DNA
      replication and chromosome dynamics in Bacillus subtilis and Archeoglobus
      fulgidus, and into the assembly of multiprotein complexes such as the type IV
      secretion system of Agrobacterium tumefaciens, and the cell division machinery of
      Escherichia coli. Genome-wide interaction networks in several species are needed
      to obtain a biologically meaningful view of the higher order organization of the
      proteome in bacteria.

PMID- 15451507
TI  - Mathematical models in microbial systems biology.
AB  - Systems biology aims at an understanding of the genotype-phenotype relations
      brought about by cellular networks. Mathematical models as formal representations
      are central for handling the associated complexity. Recently, model-based
      analysis of microorganisms has begun, for instance, to reveal functional modules
      in metabolic and transcriptional networks, to predict cellular behavior from
      genome-scale physicochemical constraints, and to suggest novel design principles
      for well-studied bacterial subsystems such as chemotaxis. Guided by common themes
      such as modularity, optimality and robustness, iterative model development
      promises further progress towards a system-level understanding.

PMID- 15451508
TI  - Order and disorder in bacterial genomes.
AB  - The availability of sequenced bacterial genomes allows a deeper understanding of
      their organizational features that are related with fundamental cellular
      processes such as coordinated gene expression, chromosome replication and cell
      division. Nevertheless, recent genome comparisons and experimental work
      highlighted the fluidity of bacterial chromosomes, including genome
      rearrangements that imperil the selective features of chromosome order. As a
      result, the clash between elements generating rearrangements and chromosome
      organization is a classic case of evolutionary conflict.

PMID- 15451509
TI  - Evolution of the mitochondrial genome: protist connections to animals, fungi and
      plants.
AB  - The past decade has seen the determination of complete mitochondrial genome
      sequences from a taxonomically diverse set of organisms. These data have allowed
      an unprecedented understanding of the evolution of the mitochondrial genome in
      terms of gene content and order, as well as genome size and structure. In
      addition, phylogenetic reconstructions based on mitochondrial DNA (mtDNA)-encoded
      protein sequences have firmly established the identities of protistan relatives
      of the animal, fungal and plant lineages. Analysis of the mtDNAs of these
      protists has provided insight into the structure of the mitochondrial genome at
      the origin of these three, mainly multicellular, eukaryotic groups. Further
      research into mtDNAs of taxa ancestral and intermediate to currently
      characterized organisms will help to refine pathways and modes of mtDNA
      evolution, as well as provide valuable phylogenetic characters to assist in
      unraveling the deep branching order of all eukaryotes.

PMID- 15451510
TI  - Analyzing protein function on a genomic scale: the importance of gold-standard
      positives and negatives for network prediction.
AB  - The concept of 'protein function' is rather 'fuzzy' because it is often based on
      whimsical terms or contradictory nomenclature. This currently presents a
      challenge for functional genomics because precise definitions are essential for
      most computational approaches. Addressing this challenge, the notion of networks
      between biological entities (including molecular and genetic interaction networks
      as well as transcriptional regulatory relationships) potentially provides a
      unifying language suitable for the systematic description of protein function.
      Predicting the edges in protein networks requires reference sets of examples with
      known outcome (that is, 'gold standards'). Such reference sets should ideally
      include positive examples - as is now widely appreciated - but also, equally
      importantly, negative ones. Moreover, it is necessary to consider the expected
      relative occurrence of positives and negatives because this affects the
      misclassification rates of experiments and computational predictions. For
      instance, a reason why genome-wide, experimental protein-protein interaction
      networks have high inaccuracies is that the prior probability of finding
      interactions (positives) rather than non-interacting protein pairs (negatives) in
      unbiased screens is very small. These problems can be addressed by constructing
      well-defined sets of non-interacting proteins from subcellular localization data,
      which allows computing the probability of interactions based on evidence from
      multiple datasets.

PMID- 15451511
TI  - The promise of functional genomics: completing the encyclopedia of a cell.
AB  - Genome sequencing provides complete parts lists of organisms. This presents the
      obvious challenge of determining how each gene contributes to the life of the
      organism. This task seems increasingly feasible; however, progress to date
      suggests that increased interaction between systematic efforts and individual
      investigators will be critical to completing the encyclopedia of the yeast cell.

PMID- 15451512
TI  - Application of proteomics to the study of platelet regulatory mechanisms.
AB  - Newly developed proteomic technologies now permit the routine identification of
      hundreds or even thousands of proteins in a single experiment. However, the
      global study of any proteome has unique challenges that set it apart from
      comprehensive studies of genes and transcripts. The detection of low-abundance,
      biologically relevant proteins poses a particular challenge, especially given
      that the dynamic range of proteins in cells is estimated to be > or =10(6).
      Nevertheless, the incorporation of proteomics into functional biochemical and
      biologic investigation has proved to be a powerful tool when applied to platelet
      biology. This review highlights recent proteomic approaches to the
      characterization of the proteins released from activated platelets and to the
      identification of integrin-associated regulators of platelet function. Also
      described are efforts to link platelet-proteomic and platelet-transcriptional
      data.

PMID- 15451513
TI  - Fascin protrusions in cell interactions.
AB  - Cell protrusions are outward extensions of the plasma membrane of individual
      cells that function in sensing the cell environment and in making initial,
      dynamic adhesions to extracellular matrix and other cells. Cell protrusions can
      be grouped into two major categories on the basis of morphology: localized,
      finger-like structures of highly defined shape and various lengths; or broad,
      irregular extensions of the plasma membrane. A key requirement of all cell
      protrusions is the need for a rigid cytoskeleton to support the localized
      extension of the plasma membrane. This is achieved either by a core unipolar
      bundle of actin microfilaments in finger-like protrusions, or by a combination of
      radial, rib-like, actin bundles integrated with a dendritic meshwork of
      microfilaments in the broad, lamellipodial protrusions. From studies of multiple
      cell types in vertebrates and invertebrates, fascin-1 has emerged as an actin
      bundling protein of general importance for a diverse set of cell protrusions with
      functions in cell adhesion, cell interactions, and cell migration. This review
      discusses current knowledge of the molecular and cellular properties and
      functions of fascin, the roles of fascin-based protrusions in the cardiovascular
      system in health and disease, and areas of future interest.

PMID- 15451514
TI  - Regulation of ryanodine receptors by FK506 binding proteins.
AB  - Ryanodine receptors (RyRs) are the major sarcoplasmic reticulum calcium-release
      channels required for excitation-contraction coupling in skeletal and cardiac
      muscle. Mutations in RyRs have been linked to several human diseases. Mutations
      in the cardiac isoform of RyR2 are associated with catecholaminergic polymorphic
      ventricular arrhythmias (CPVT), and arrhythmogenic right ventricular dysplasia
      type 2 (ARVD2), whereas mutations in the skeletal muscle isoform (RyR1) are
      linked to malignant hyperthermia (MH) and central core disease (CCD). RyRs are
      modulated by several other proteins, including the FK506 binding proteins
      (FKBPs), FKBP12 and FKBP12.6. These immunophilins appear to stabilize a closed
      state of the channel and are important for cooperative interactions among the
      subunits of RyRs. This review discusses the regulation of RyRs by FKBPs and the
      possibility that defective modulation of RyR2 by FKBP12.6 could play a role in
      heart failure, CPVT, and ARVD2. Also discussed are the consequences of FKBP12
      depletion to skeletal muscle and the possibility of FKBP12 involvement in certain
      forms of MH or CCD.

PMID- 15451515
TI  - The development of the embryonic outflow tract provides novel insights into
      cardiac differentiation and remodeling.
AB  - The embryonic cardiac outflow tract (OFT) connects the developing ventricles with
      the aortic sac. In birds and mammals, OFT cardiomyocytes are generated from a
      "secondary (anterior)," heart-forming field well after the formation of the
      primitive heart tube. The OFT cardiomyocytes have unique properties and
      developmental fates as compared with the myocytes of the atrial and ventricular
      chambers. Many of the OFT cardiomyocytes of the avian embryo are eliminated by
      programmed cell death (PCD) during OFT remodeling in the transition from a single
      to a dual-series circulation. Targeted PCD gain and loss-of-function studies
      indicate that PCD drives the shortening and rotation of the OFT required for the
      aorta and pulmonary artery to connect with the left and right ventricles,
      respectively. Defects in this process model aspects of the relatively common and
      often life-threatening congenital human conotruncal heart defects. Using
      indicators of tissue hypoxia, we suggest that OFT myocardial hypoxia may be the
      trigger for the PCD-dependent remodeling of the OFT. This review discusses these
      aspects of the formation and remodeling of the embryonic OFT in the context of
      the broader questions of cardiac muscle biology.

PMID- 15451516
TI  - An emerging role for Kruppel-like factors in vascular biology.
AB  - The Kruppel-like family of transcription factors play diverse roles regulating
      cellular differentiation and tissue development. Accumulating evidence supports
      an important role for these factors in vascular biology. This review examines the
      current knowledge of this gene family's role in key cell types that critically
      regulate vessel biology under physiologic and pathologic states.

PMID- 15451517
TI  - Coronary vessel development: the epicardium delivers.
AB  - Coronary artery disease accounts for 54% of all cardiovascular disease in the
      United States. Understanding how coronary vessels develop is likely to uncover
      novel drug targets and therapeutic strategies that will be useful in directing
      the repair or remodeling of coronary vessels in adults. Recent insights have
      identified the importance of cells derived from the proepicardium and epicardium
      in the formation of coronary vessels. This article reviews the basic steps in
      coronary vessel development, the molecules implicated in these steps, and the
      pressing questions awaiting answers.

PMID- 15451518
TI  - Molecular restoration of beta-adrenergic receptor signaling improves contractile
      function of failing hearts.
AB  - beta-adrenergic receptor (betaAR) antagonists, or beta blockers, are now a part
      of the standard therapeutic arsenal in the medical management of chronic heart
      failure (HF). Conversely, betaAR stimulation remains the most efficient way to
      enhance cardiac contractile function acutely, although long-term inotropic
      therapy based on enhanced betaAR stimulation is likely detrimental. Although
      altered betaAR signaling plays a pivotal role in the genesis of HF, the choice to
      therapeutically agonize or antagonize this receptor pathway remains an area of
      ongoing investigation. Research from the authors' laboratory as well as other
      research conducted over the last 10 years has produced evidence to support the
      fact that "normalizing" the betaAR system at a molecular level and improving
      signaling, instead of blocking it, leads to significant enhancement of cardiac
      contractile function and prevents ventricular remodeling in HF. This review
      summarizes the extensive in vivo animal model experimentation that supports the
      still-controversial hypothesis that increasing the myocardial density of beta(2)
      ARs or, more effectively, inhibiting the activity of the betaAR kinase (also
      referred to as G-protein-coupled receptor kinase 2), represent potential novel
      therapeutic strategies for HF.

PMID- 15451519
TI  - Hetero-stereocomplexes of D-poly(lactic acid) and the LHRH analogue leuprolide.
      Application in controlled release.
AB  - Reversible hetero-stereoselective complexes were obtained by mixing acetonitrile
      solutions of enantiomeric D-poly(lactic acid) (d-PLA) and leuprolide, an L
      configured nonapeptide LHRH analogue. The complex spontaneously aggregated and
      precipitated in high yields (95%) from acetonitrile solutions, forming uniform,
      porous microparticles with a mean unweighed particle size of 1.7 microm. The
      complexation of L-configured peptide occurred only with D-PLA, and not with L-PLA
      or racemic D,L-PLA. Various factors affecting the release pattern of leuprolide
      from the hetero-stereocomplexes were investigated. Complexes with D-PLA of low
      molecular weight (< 10,000 Da) displayed lower release rates of leuprolide than
      high molecular weight D-PLA (> 50,000 Da). Changing the leuprolide: D-PLA ratio
      from 1:50 to 1:10 (w/w) in the stereocomplex, resulted in a faster release of
      leuprolide. Similarly, the release rate of leuprolide was twice as fast when
      adding poly(ethylene glycol) to the acetonitrile complexation solution.
      Leuprolide was released from most of the formulations in a first order pattern,
      with only a small burst release during the first 24 h. Addition of water to the
      complexation solution significantly increased the initial release of the peptide.
      Low testosterone levels for over 25 days were observed in an in vivo release
      study of leuprolide from a hetero-stereocomplex formulation, monitoring
      testosterone levels in the blood of rats after sub cutaneous injection.

PMID- 15451520
TI  - In vitro study of the immune stimulating activity of an atrophic [correction of
      athrophic] rhinitis vaccine associated to chitosan microspheres.
AB  - Chitosan microspheres (CMs) were prepared by an ionic gelation process with
      tripolyphosphate and characterized. Bordetella Bronchiseptica Dermonecrotoxin
      (BBD), a major virulence factor of a causative agent of atrophic rhinitis (AR),
      was loaded on to the CMs for nasal vaccination. BBD-loaded CMs were observed as
      aggregated shapes although unloaded CMs were observed as relatively spherical
      ones. The average particle size of the BBD-loaded CMs was 4.39 microm. The lower
      the molecular weight of chitosan and the higher the medium pH, the greater was
      the release of BBD from the BBD-loaded CMs in vitro due to weaker intermolecular
      interaction between chitosan and BBD. Tumor necrosis factor alpha and nitric
      oxide from RAW264.7 cells exposed to BBD-loaded CMs were gradually secreted with
      time, suggesting that released BBD from CMs had immune stimulating activity of AR
      vaccine in vitro.

PMID- 15451521
TI  - Insulin-loaded W/O/W multiple emulsions: comparison of the performances of
      systems prepared with medium-chain-triglycerides and fish oil.
AB  - Insulin-loaded W/O/W multiple emulsions (ME) composed of medium-chain
      triglycerides have been shown to decrease the blood glucose level after oral
      administration to diabetic rats. Fish oil (very long-chain triglycerides) could
      be an alternative to medium-chain triglycerides because its chronic consumption
      has beneficial therapeutic effects. The aim of this work was twofold: to obtain
      stable fish oil containing ME, based on a formulation optimized in a previous
      work with low medium-chain triglycerides content, and to compare their
      characteristics to those of ME composed of medium-chain triglycerides. Due to the
      higher viscosity and surface tension of fish oil compared to medium-chain
      triglycerides, preparation of ME appeared difficult to achieve. However, a stable
      unloaded-ME with low fish oil content was formed, by adapting the emulsification
      process. The characteristics of unloaded fish oil ME were almost similar to those
      of medium-chain triglycerides ME. In contrast to medium-chain triglycerides ME,
      the introduction of insulin did not improve the elasticity and consequently the
      characteristics and stability of fish oil ME. Nevertheless, the insulin-loaded
      fish oil containing ME was shown to be stable for 6 weeks at 4 degrees C.

PMID- 15451522
TI  - Poly(lactic acid) nanoparticles labeled with biologically active Neutravidin for
      active targeting.
AB  - In this study, NeutrAvidin was covalently bound to the surface of poly(DL-lactic
      acid) (PLA) nanoparticles, with the aim of attaching targeting compounds, such as
      proteins, to their surface. Sulfhydryl groups were first introduced on the
      surface of PLA nanoparticles through a carbodiimide reaction. NeutrAvidin was
      then bound to the thiolated nanoparticles via a bifunctional cross-linker, which
      offers two binding sites, one for primary amine groups and one for thiol
      functions. The amount of sulfhydryl groups obtained on the surface of the
      nanoparticles was determined. The NeutrAvidin -labeled nanoparticles were
      evaluated with respect to particle size, protein concentration and biotin binding
      capacity. The concentration of thiol functions on the surface of nanoparticles
      was 105 +/- 15 mmol/mol PLA. The quantification of NeutrAvidin coupled to the
      nanoparticles revealed that a significant amount of the protein was covalently
      bound to the nanoparticles. The concentration of NeutrAvidin bound to the
      nanoparticles could be controlled by varying the amount of protein during the
      coupling reaction. The maximum concentration of NeutrAvidin attached to the
      particles was 6 mmol per mol of PLA. The specific activity of NeutrAvidin bound
      to the nanoparticles was also evaluated and results revealed that the protein
      maintained the capacity to bind biotin. The activity of the NAR-labeled
      nanoparticles was lower than expected, due to the undesired aggregation of the
      native NeutrAvidin. Altogether, the results suggest that other proteins, such as
      antibodies could be coupled to the nanoparticles for active targeting.
      Furthermore, PLA nanoparticles bearing NeutrAvidin are interesting candidates for
      active targeting with biotinylated antibodies using the biotin-avidin interaction
      in a two step procedure.

PMID- 15451523
TI  - Transfection of a mouse dendritic cell line by plasmid DNA-loaded PLGA
      microparticles in vitro.
AB  - Targeting of DC for DNA vaccination may be achieved by DNA-loaded poly(lactide-co
      glycolide) (PLGA) biodegradable microparticles, since DC efficiently capture
      these microparticles in vitro and in vivo. DNA was encapsulated in PLGA
      microparticles by spray-drying. Various additives were tested and process
      parameters adjusted in order to prevent degradation of the DNA during
      encapsulation. The highest degree of supercoiled DNA was maintained by adding a
      strong buffering agent, such as PBS or NaHCO(3), whereas the cryoprotective
      lactose did not show a significant protective effect. DNA-containing PLGA
      microparticles were administered to a mouse DC line. Transfection efficacy was
      compared with commonly employed cationic transfectants and was visually assessed
      by green fluorescent protein expression. Transfection rate was very low in DC for
      all microparticle formulations and was comparable with commonly used cationic
      transfectants. It is concluded that the transfection of DC using PLGA
      microparticles is feasible, but efforts need to be undertaken to improve
      transfection efficiency in vitro, which may in addition lead to improved immune
      responses in vivo.

PMID- 15451524
TI  - Plasmid-DNA loaded chitosan microspheres for in vitro IL-2 expression.
AB  - Interleukin-2 (IL-2) expression plasmid (pCXWN-hIL-2) loaded chitosan
      microspheres were evaluated for using in gene-based immunotherapy. Chitosan
      microspheres containing pCXWN-hIL-2 were prepared by using a precipitation
      technique. In addition, the effects of different factors such as the
      concentration (0.35-0.70%) and the molecular weight of chitosan (low and medium
      molecular weights), the plasmid amount (5-10 microg/ml) and the presence of
      glutaraldehyde during the encapsulation process, on microsphere characteristics
      were investigated. The size of microspheres changed between 1.45 and 2.00 microm.
      All the formulation factors affected the size of microspheres. The structure of
      plasmid remained unchanged during the encapsulation process and the release
      studies. Plasmid encapsulation efficiency of chitosan microspheres was high (82
      92%). The zeta potential values of microspheres was approximately +5.2 to +12.4
      mV. In vitro release properties of microspheres changed with formulation
      variables. In vitro release of DNA changed with the concentration and molecular
      weight of chitosan and initial plasmid amount. Addition of glutaraldehyde is not
      necessary for a formulation. MAT-LyLu, the rat prostate adenocarcinoma cell line,
      was used for the determination of the in vitro transfectional activity of IL-2
      encoding plasmid DNA loaded chitosan microspheres and the level of IL-2 expressed
      into the cells was assayed using a ELISA kit. High level of IL-2 expression was
      obtained with plasmid-loaded chitosan microspheres. Microspheres showed similar
      IL-2 production as lipofectin. The molecular weight of chitosan used and the
      amount of plasmid influenced the in vitro IL-2 production in the cells.
      Encapsulation of IL-2 encoding gene into chitosan microspheres might be a useful
      strategy to increase the expression and to control the delivery of cytokine gene
      to cells.

PMID- 15451525
TI  - The effect of cholate on solubilisation and permeability of simple and protein
      loaded phosphatidylcholine/sodium cholate mixed aggregates designed to mediate
      transdermal delivery of macromolecules.
AB  - Carriers for non-invasive administration of biologically important antioxidant
      enzymes Cu,Zn-superoxide dismutase (SOD) and catalase (CAT) were developed.
      Solubilisation and permeabilities of various soybean phosphatidylcholine/sodium
      cholate (SPC/NaChol) mixtures, mainly in the form of lipid bilayers, focussing on
      system properties relevant for non-invasive enzyme delivery were investigated in
      this work. Static and dynamic light scattering measurements gave information on
      the behaviour of the systems containing up to 40 mM NaChol and 30.6-1.2 mM SPC in
      the final suspension. The average size of such mixed aggregates was in the 100
      200 nm range. Suspension turbidity decreased by 50% upon increasing nominal molar
      detergent/lipid ratio to NaChol/SPC = 7 and 1.25, in case of SPC = 1.2 and 19.6
      mM, respectively. The effective NaChol/SPC molar ratio in bilayers saturated with
      the detergent was found to be: R(e)(sat) = 0.70 +/- 0.01; bilayer solubilisation
      point corresponded to R(e)(sol) = 0.97 +/- 0.02, independently of enzyme loading.
      Vesicles became very permeable to SOD when membrane bound NaChol concentration
      exceeded 13.7 mM, in case of total starting lipid concentration of 138 mM diluted
      to SPC = 19.6 mM. Specifically, we measured a 50% loss of SOD from the vesicles
      with an aggregate-associated molar detergent ratio NaChol/SPC approximately 0.7,
      which is near the saturation but well below the solubilisation limit. Calcein
      efflux from such vesicles was compared with SPC/NaChol/SOD mixed aggregates. Our
      results should contribute to the future design of vesicle mediated transdermal
      delivery of antioxidant enzymes.

PMID- 15451526
TI  - Engineered microcrystals for direct surface modification with layer-by-layer
      technique for optimized dissolution.
AB  - This investigation relates to a two-step formulation development technique
      synthesis of sterically stabilized drug microcrystals followed by direct surface
      modification by sequential electrostatic adsorption. Stable microcrystals of
      naproxen were produced by pH-induced reprecipitation in presence of a stabilizer.
      Sequential layer growth was achieved by the layer-by-layer assembly of
      biocompatible polyelectrolytes (PEs) and was registered using
      microelectrophoresis. The coated colloids were characterized using confocal laser
      scanning microscopy (CLSM) and scanning electron microscopy (SEM). The in vitro
      controlled release pattern of the drug through the PE diffusion barrier was
      studied using a diffusion cell assembly at physiological pH of 7.4, both before
      and after freeze-drying. Thermodynamically stable naproxen microcrystals were
      obtained by association and had a mean length of 15 microm and a zeta potential
      of -37.5 mV and were surface modified efficiently using biocompatible
      polysaccharide/protein-based PEs. Sufficient charge reversal with each layer was
      evident indicating layer growth with successive deposition cycles. The coating
      was complete and homogeneous as visualized under CLSM and SEM. The in vitro
      release study revealed that the stoichiometry of PEs in the complex coating and
      its molecular architecture played important roles in forming the diffusion
      barrier, which offered efficient control of the dissolution rate of drug core (up
      to 50% lower than bare crystal). The release profile fitted zero order release
      kinetics. This novel formulation technique enables administration of high
      concentrations of water-insoluble drugs in a stable, tissue compatible form,
      simultaneously affording sustained release.

PMID- 15451527
TI  - Spray freezing into liquid nitrogen for highly stable protein nanostructured
      microparticles.
AB  - The objectives of this study were to produce nanostructured protein
      microparticles with the spray freezing into liquid (SFL) cryogenic process and to
      demonstrate a smaller degree of protein denaturation and aggregation than
      observed in spray freeze drying (SFD). Nanostructured microparticles were formed
      by atomization of an aqueous buffer solution containing bovine serum albumin
      (BSA) with and without excipients beneath the surface of a cryogenic liquid.
      Lyophilization was used to sublime the water in the frozen particles. The
      resulting BSA dry powder was characterized by size exclusion chromatography,
      Fourier-transform infrared spectroscopy, scanning electron microscopy (SEM),
      light scattering, and specific surface area analysis. SEM revealed highly porous
      microparticle with features smaller than 500 nm. The specific surface area of the
      BSA microparticles ranged from 19.2 to 97.7 m(2)/g as a function of the total
      protein and excipient content in the aqueous feed solution. SFL produced less
      denaturation and aggregation of protein monomer than SFD, despite the extremely
      high surface areas in both processes. The intense atomization and ultra-rapid
      freezing in the SFL process lead to nanostructured BSA microparticles with high
      surface areas. Protein denaturation and aggregation are reduced in SFL relative
      to SFD. The more rapid freezing in SFL lowers the time for proteins to aggregate
      or diffuse to water-air and water-ice interfaces where they may be denatured.

PMID- 15451528
TI  - The influence of the use of viscosifying agents as dispersion media on the drug
      release properties from PLGA nanoparticles.
AB  - Poly(lactide-co-glycolide) nanoparticles incorporating ciprofloxacin HCl were
      prepared by means of a W/O/W emulsification solvent evaporation method. The
      physicochemical properties of these particles were evaluated by measuring
      particle size, zeta potential and drug loading efficiency. Gamma-sterilised
      nanoparticles were dispersed in different isoviscous polymer solutions, commonly
      used as vehicles in eye drops. The influence of gamma-irradiation of the
      viscosifying agents on the drug release properties of the dispersed nanoparticles
      was evaluated with respect to release in mannitol solution. The viscosity of the
      polymer solutions prepared was measured by flow rheometry and thereby the
      influence of temperature and sterilisation by autoclaving on viscosity was
      examined. Before and after freeze-drying and subsequent sterilisation by gamma
      irradiation, the polymer solutions were also characterised by dynamic stress
      sweep and dynamic frequency sweep oscillation measurements to deduce possible
      structural changes. A possible relationship between the differences in
      ciprofloxacin release from the nanoparticles suspended in the various media and
      the network structure or rheological behaviour of the polymers was investigated.

PMID- 15451529
TI  - Qualitative proof of liquid dispersion and penetration-involved granule formation
      in a high shear mixer.
AB  - The origination of granules in the early seconds is an important aspect of high
      shear granulation. To elucidate these mechanisms, a substandard amount (1.5% w/w)
      of an aqueous hydroxypropyl cellulose solution was added to four different
      lactose mixtures: (1) lactose 100 M (d(4,3) approximately 170 microm), (2)
      lactose 200 M (d(4,3) approximately 50 microm), and (3, 4) 10% magnesium
      stearate/lactose 100 or 200 M. Between 1 and 15 s after binder addition samples
      were taken, which were immediately frozen in liquid nitrogen. The frozen sample
      was sieved into granular (> 280 microm) and non-granular-material (< 280 microm).
      The binder distribution in these fractions was determined. The observed binder
      distribution behaviour revealed that three different nucleation mechanisms can
      occur: (I) For lactose 100 M holds that all the binder is initially located in
      the granules. These granules are subsequently broken again. (II) The lactose 200
      M granules also contain 100% of the added binder liquid. Contrary to lactose 100
      M the lactose 200 M granules remain intact during the process. It is argued that
      in both cases liquid penetration is responsible for the accumulation of all
      liquid in the granules. A theoretical evaluation also confirmed that liquid
      penetration leads to the formation of the primary granules (III) No liquid
      penetration is possible in the hydrophobic magnesium stearate/lactose mixtures
      and the binder is completely dispersed in the non-granular material.

PMID- 15451530
TI  - Liquid and semisolid SLN dispersions for topical application: rheological
      characterization.
AB  - Aqueous dispersions of solid lipid nanoparticles (SLN) are promising drug carrier
      systems for topical application. A drawback, however, is the need of
      incorporating the SLN dispersion in commonly used dermal carriers (creams, gels)
      to obtain the required semisolid consistency for dermal application. This study
      describes the production of SLN dispersions having the desired semisolid
      consistency by a one-step process. Physical characterization of these systems in
      terms of particle size and rheological properties revealed some interesting
      features. Despite the high lipid content it was possible to produce colloidal
      dispersions by high pressure homogenization. Continuous flow measurements
      revealed systems with yield point, plastic flow and thixotropy. Oscillation
      measurements proved the viscoelastic microstructure of the SLN dispersions.
      Higher concentrated SLN dispersions were found to have a prevailing elastic
      component in contrast to lower concentrated systems. Viscoelastic properties of a
      40% SLN dispersion were found to be comparable to standard dermal preparations.
      Storage stability at room temperature in terms of particle size could be
      demonstrated over a 6-month period. The development of the gel structure of
      semisolid SLN dispersions is delayed comparable to commercial O/W creams with non
      ionic emulsifiers. Parameters like concentration of the dispersed phase, particle
      size and particle shape were identified as significant factors influencing the
      microstructure of these complex semisolid systems.

PMID- 15451531
TI  - Compaction of crystallographic forms of pharmaceutical granular lactoses. I.
      Compressibility.
AB  - Physico-chemical properties of a substance including the compaction behaviour are
      directly connected with the crystalline structure. The aim of this work is to
      compare the compaction behaviour in a group of excipient and in this first part,
      to display the influence of lactose structures on the compressibility. alpha
      Lactose monohydrate (LalphaM), anhydrous beta-lactose (LbetaA), anhydrous alpha
      lactose (LalphaA) and partly amorphous lactose (FF) were compressed using
      instrumented presses to investigate the densification behaviour under pressure.
      Force-displacement curves were associated to two energy parameters, specific
      cycle energy and specific expansion energy. This approach was used to class the
      four lactose species. It is possible to differentiate three groups with the
      specific energy cycle, FF, LalphaA/LbetaA and LalphaM in decreasing order of this
      energy. At the same time, the values of specific expansion energy are relatively
      low for FF and LalphaA contrary to LalphaM and LbetaA. Then, Heckel's plots were
      obtained with two compact geometries and the mean yield pressure was calculated
      from the in-die-method and the out-of-die-method. Two lactoses seem to differ,
      LalphaM appears to be the most ductile whereas LalphaA is more brittle than the
      others. Finally, it is concluded, that in the case of lactoses,
      pseudopolymorphism seems to affect the compressibility more than anomerisation or
      partial amorphisation.

PMID- 15451532
TI  - Compaction of crystallographic forms of pharmaceutical granular lactoses. II.
      Compacts mechanical properties.
AB  - It is well known that the choice of the crystal form affects the physicochemical
      properties such as compaction behaviour. In this work, the mechanical properties
      of compacts obtained from compaction of lactoses by using a micropress prototype
      are calculated. Tensile strength, Young's modulus, toughness and Brinell hardness
      were measured and used to compare the various crystalline forms: alpha-lactose
      monohydrate (LalphaM), anhydrous beta-lactose (LbetaA), anhydrous alpha-lactose
      (LalphaA) and partly amorphous lactose (FF). With all the mechanical properties
      measured, the lactoses could be differentiated. Then, the specific energy of
      failure G*(IC) was obtained from the toughness and the Young's modulus for each
      lactose. LalphaM showed small specific energy of failure due to its low toughness
      which is not balanced by its Young's modulus. The highest values were obtained
      with the two anhydrous forms, LalphaA and LbetaA. Finally, these mechanical
      properties were linked with general compaction behaviour and cohesive energy
      density which is a characterization at a molecular level.

PMID- 15451533
TI  - Characteristics of a novel phospholipid-based depot injectable technology for
      poorly water-soluble drugs.
AB  - Phospholipid concentrates in a water miscible solvent were explored as injectable
      formulations for the poorly water-soluble drugs, using the anti-infective PHA 244
      as model substance. Formulations containing up to 70% w/v phospholipid could
      dissolve 15% PHA 244. The formulations showed excellent syringe-ability and no
      precipitation of the drug after dilution in an excess of water. The local
      tolerability and pharmacokinetics of the formulations were explored after
      subcutaneous injection into cattle. A slow release pattern over a 2-week period
      and excellent local tolerability at the injection site were observed. Considering
      the low manufacturing costs, related to the production of solutions, this
      SupraVail MLM (Membrane Lipid Matrix) technology is a cost-effective alternative
      to more expensive depot technologies for poorly water-soluble drugs with similar
      release characteristics, like sterile aqueous and oily drug substance
      suspensions, as cited in the literature.

PMID- 15451534
TI  - Aerosolisation of beclomethasone dipropionate using spray dried
      lactose/polyethylene glycol carriers.
AB  - The aim of this study was to characterize the physical properties of spray dried
      lactose in the presence of different polyethylene glycols (PEG 400, PEG 3000 and
      PEG 6000) and to evaluate their performance as carriers for dry powder inhaler
      (DPI) formulations. The efficiency of spray dried lactose/PEG carriers in
      aerosolisation of beclomethasone dipropionate (BD), a model hydrophobic drug, was
      compared to Pharmatose 325 M (L325), spray dried lactose alone (SDL), and also a
      sieved (< 38 microm) fraction of alpha-lactose monohydrate (SL). In vitro
      deposition analysis was performed using a twin stage liquid impinger at a flow
      rate of 60 l/min through a Spinhaler. The deposition profiles of the drug from
      binary formulations composed of BD and spray dried lactose/PEG carriers were also
      compared to ternary formulations containing large and fine lactose carriers.
      Differential scanning calorimetry and X-ray diffraction data showed the presence
      of alpha-anhydrous lactose in spray dried lactose/PEG crystalline powders. Spray
      drying of lactose in the presence of PEG 400 resulted in the production of a
      powder (SDL-PEG400) with lower alpha-lactose monohydrate content, and also
      smaller particle size distribution than those obtained in the presence of PEG
      3000 (SDL-PEG3000) or PEG 6000 (SDL-PEG6000). All formulations showed different
      deposition profiles, except those containing SDL-PEG3000 or SDL-PEG6000 which
      exhibited similar data. The fine particle fraction of aerosolised BD varied from
      6.26 +/- 1.07 (for L325) to 25.87 +/- 5.33 (for SDL-PEG3000). All deposition
      profiles of BD aerosolised from SDL-PEG3000 were significantly higher (P < 0.01)
      than those produced by binary and ternary formulations containing L325, a coarse
      lactose commercially available for DPI formulations. The differences observed in
      deposition data for various carriers were interpreted according to their physical
      properties. It was concluded that particle size distribution, morphology and
      specific surface texture of SDL-PEG3000 and SDL-PEG6000 were important factors
      influencing their efficiency as small carriers for DPI formulations.

PMID- 15451535
TI  - Once-daily propranolol extended-release tablet dosage form: formulation design
      and in vitro/in vivo investigation.
AB  - The purpose of this study was to develop and optimize the propranolol once-daily
      extended release formulations containing HPMC, Microcrystalline cellulose (MCC)
      and lactose. In vitro studies, the response surface methodology and multiple
      response optimization utilizing the polynomial equation were used to search for
      the optimal formulation with specific release rate at different time intervals.
      The constrained mixture experimental design was used to prepare systematic model
      formulations, which were composed of three formulation variables: the content of
      HPMC (X(1)) MCC (X(2)) and lactose (X(3)). The drug release percent at 1.5, 4, 8,
      14 and 24 h were the target responses and were restricted to 15-30, 35-55, 55-75,
      75-90 and 90-110%, respectively. The results showed that the optimized
      formulation provided a dissolution pattern equivalent to the predicted curve,
      which indicated that the optimal formulation could be obtained using response
      surface methodology. The mechanism of drug release from HMPC matrix tablets
      followed non-Fickian diffusion. In the vivo study, the MRT was prolonged for
      matrix tablets when compared with commercial immediate release tablets.
      Furthermore, a linear relationship between in vitro dissolution and in vivo
      absorption was observed in the beagle dogs.

PMID- 15451536
TI  - Development of an intravenously injectable chemically stable aqueous omeprazole
      formulation using nanosuspension technology.
AB  - Omeprazole is a proton pump inhibitor, which is used for the treatment of peptic
      ulcers, reflux esophagitis and Zollinger-Ellison syndrome. It is a poorly
      soluble, chemically labile drug with a high degradation rate in aqueous media.
      The aim of this study was to show the feasibility of omeprazole stabilization
      using the DissoCubes technology and to find optimal production parameters for a
      stable, highly concentrated omeprazole nanosuspension. The high performance
      liquid chromatography analysis has proved the predominance of the nanosuspension
      produced by high pressure homogenization in comparison to an aqueous solution.
      Even 1 month after production no discoloration or drug loss was recognizable when
      the nanosuspension was produced at 0 degree C. As a result it can be stated that
      the production of nanosuspensions by high pressure homogenization is suitable for
      preventing degradation of labile drugs.

PMID- 15451537
TI  - W/O/W multiple emulsions with diclofenac sodium.
AB  - The disperse oil droplets of W/O/W multiple emulsions contain small water
      droplets, in which drugs could be incorporated, but the structure of these
      emulsions is also the reason for possible instability. Due to the middle oil
      phase which acts as a 'semipermeable' membrane the passage of water across the
      oil phase can take place. However, the emulsions have been produced in a two-step
      production process so not only the leakage of encapsulated drug molecules out of
      the inner water phase during storage but also a production-induced reduction of
      the encapsulation rate should be considered. The aim of this study was to
      ascertain how far the production-induced reduction of the encapsulation rate
      relates to the size of inner water droplets and to evaluate the relevance of
      multiple emulsions as drug carrier for diclofenac sodium. Therefore multiple
      emulsions were produced according to a central composite design. During the
      second production step it was observed that the parameters pressure and
      temperature have an influence on the size of the oil droplets in the W/O/W
      multiple emulsions. Further experiments with different W/O emulsions resulted in
      W/O/W multiple emulsions with different encapsulation rates of diclofenac sodium,
      due to the different sizes of the inner water droplets, which were obtained in
      the first production step.

PMID- 15451538
TI  - The solubilization of the poorly water soluble drug nifedipine by water soluble 4
      sulphonic calix[n]arenes.
AB  - In this study, the solubilizing effect of 4-sulphonic calix[n]arenes on the
      poorly water soluble drug nifedipine was investigated. 4-Sulphonic calix[n]arenes
      are water-soluble phenolic cyclooligomers that form complexes with neutral
      molecules such as nifedipine. Solubility experiments were performed at 30 degrees
      C using the Higuchi rotating bottle method. The amount of nifedipine in solution
      was determined by HPLC. The results showed that the size of the 4-sulphonic
      calix[n]arenes, the pH of solubility medium, and the concentration of the
      calix[n]arenes all significantly changed the solubility of nifedipine. 4
      Sulphonic calix[8]arene improved the solubility of nifedipine the most, about 3
      times the control at 0.008 M and pH 5, followed by 4-sulphonic calix[4]arene,
      about 1.5 times the control at 0.008 M and pH 5, while in the presence of 4
      sulphonic calix[6]arene, the solubility of nifedipine was decreased. The possible
      mechanisms involving in the complexation between 4-sulphonic calix[4]arenes, 4
      sulphonic calix[8]arene and nifedipine may be a combination of hydrogen bonding,
      hydrophobic bonding, and possibly electron donor-acceptor interactions. However,
      the degree to which these forces promote the formation of nifedipine:4-sulphonic
      calix[n]arene complexes with increased solubility was limited by conformational
      changes in the 4-sulphonic calix[n]arene molecules.

PMID- 15451539
TI  - Characterisation of nimesulide-betacyclodextrins systems prepared by
      supercritical fluid impregnation.
AB  - The purpose of this study was to apply the supercritical CO(2) impregnation
      process for preparing solvent-free nimesulide (NMS)-betacyclodextrins (BCD)
      association systems with enhanced drug dissolution rate. Several drug-to-carrier
      molar ratios were tested (1:1; 1:2.5; 1:3.5) at different conditions of
      temperatures (40, 100, and 130 degrees C) and pressures (140, 190 or 220 bar).
      The physical and morphological characterisation of the systems using powder X-ray
      diffraction, thermal analysis, diffuse reflectance Fourier transform-infrared
      spectroscopy and scanning electron microscopy was carried out to understand the
      influence of this technological process on the physical status of single
      components and binary systems and to detect possible interactions between drug
      and carrier. These analyses provided no evidence of a complete inclusion of NMS
      in the carrier but the existence of interactions between drug and carrier
      together with a partial dehydration of the BCD and the formation of drug
      crystallites with lower melting point and heat of fusion than the native NMS.
      These phenomena were more intense when severe conditions of pressure and
      temperature (220 bar and 130 degrees C) were used during impregnation trials and
      when the amount of BCD augmented in the systems. These activated solid state of
      the impregnated systems promoted an enhancement of drug dissolution rate that, in
      keeping with the results of the physical characterisation, was function of the
      process conditions and BCD content.

PMID- 15451540
TI  - Comparison of skin transport and metabolism of ethyl nicotinate in various
      species.
AB  - The skin transport and metabolism characteristics of ethyl nicotinate (EN) in
      rabbit, rat, guinea-pig, pig, shed snake skin and human were compared. In vitro
      skin transport using excised skin and hydrolysis experiments using skin
      homogenate were carried out. Flux of EN, a metabolite, nicotinic acid (NA), and
      the total (EN + NA), as well as kinetic parameters (V(max) and K(m)) for
      hydrolysis of EN were determined and compared among various species. The
      enzymatic conversion of EN to NA was observed for all skin permeation
      experiments. Total flux from EN-saturated solution between rabbit, rat, guinea
      pig and human was significantly different (P < 0.05). A great difference between
      species was observed in skin esterase activity. The NA/total flux ratio of human
      was significantly lower than that of rabbit, rat or guinea-pig but lower than
      that of shed snake skin (P < 0.05). There is no significant difference in skin
      permeation and metabolism between human and pig (P > 0.05). Total flux increased
      linearly with an increase in EN donor concentration for all species. For pig,
      shed snake skin and human, NA flux increased with an increase in EN donor
      concentration and reached a plateau, suggesting the metabolic saturation was
      taking place in the skin. NA flux at plateau and EN donor concentration in which
      the NA flux reached a plateau were also affected by species difference. These
      findings indicated that the discrepancy in transdermal profiles of EN among
      species tested was predominantly due to the difference in the esterase activity
      in the skin.

PMID- 15451541
TI  - Improvement of lipophilicity and membrane transport of cefuroxime using in vitro
      models.
AB  - Most beta-lactam antibiotics cannot be absorbed orally and, therefore, must be
      administered intravenously (i.v.) or intramuscularly (i.m.). Because of the
      obvious drawbacks of drug delivery by injection, the development of alternatives
      with enhanced oral bioavailability is receiving much attention in pharmaceutical
      research. Cefuroxime exhibiting significant advantages in the parental treatment
      of common infections, was used as model drug in the present study. The effect of
      the cationic absorption enhancers (four quaternary ammonium salts) on the
      lipophilicity of cefuroxime was investigated by means of the n-octanol/water
      system. The results on partitioning coefficients in the n-octanol/buffer system
      were confirmed using an in vitro transport model with artificial (dodecanol
      collodium membrane) and biological membranes (Charles-River guinea pig).

PMID- 15451542
TI  - A possibility to predict the absorbability of poorly water-soluble drugs in
      humans based on rat intestinal permeability assessed by an in vitro chamber
      method.
AB  - This paper describes a means to predict the absorbability of poorly water-soluble
      drugs in humans based on rat intestinal permeability assessed by the in vitro
      Ussing-type chamber method. We investigated the correlation between the apparent
      permeability coefficients (P(app)) of 10 water-soluble drugs obtained by the in
      vitro chamber method, in which the excised rat small intestinal tissue was used
      as the membrane, and the fractions absorbed (F(a)) in humans. Using this
      correlation, we predicted F(a) values of 5 poorly water-soluble drugs based on
      their P(app) obtained through our modified chamber method using an additive. For
      water-soluble drugs, a good correlation between P(app) and F(a') expressed by the
      equation: F(a) = 1 - exp(-P(app) x 1.51 x 10(5))(r(2) = 0.920), was found. The
      poorly water-soluble drugs used in the present study could be solubilized with 5%
      (final concentration) dimethylsulfoxide, and their P(app) could be obtained
      through our modified chamber method. For poorly water-soluble drugs whose
      dose:solubility ratio ranged from 2500 to 3500 ml, predicted F(a) values were
      favorably comparable with their F(a) values reported in humans in the literature.
      These results showed that the in vitro Ussing-type chamber method was a useful
      method for predicting the F(a) of poorly water-soluble drugs.

PMID- 15451543
TI  - Evaluation of the bioavailability of flurbiprofen and its beta-cyclodextrin
      inclusion complex in four different doses upon oral administration to rats.
AB  - The dissolution profiles of flurbiprofen (Flu) and its beta-cyclodextrin
      inclusion complex (Flu/beta-CD) in buffer solutions at various pH values were
      examined. The percent dissolved at 15 min for Flu and Flu/beta-CD was almost 100%
      at pH 6.8 and 8.0 but the dissolution rate of Flu was extremely reduced at pH 1.2
      and 4.0. In these lower pH conditions, Flu/beta-CD improved the dissolution rate
      of Flu. The percent dissolved at 1 h for Flu/beta-CD at pH 1.2 and 4.0 were 33.4
      and 41.3%, respectively, and about 10 times larger than those for Flu. The oral
      bioavailability of Flu from Flu or Flu/beta-CD at doses of 1, 3, 10, and 30 mg/kg
      (as Flu) was examined in rats. An apparent linear relationship between doses and
      C(max) and AUC was observed after administration of Flu and Flu/beta-CD. The Flu
      C(max) and AUC values at 30 mg/kg, however, were much lower than would have been
      predicted from doses of 1-10 mg/kg. Those of Flu/beta-CD were also lower than the
      predicted values, but the gap was quite small. The results suggest that the
      absorption of Flu in rats was saturated at 10 mg/kg, and that the enhanced
      dissolution rate of Flu/beta-CD increased the saturation dose to 30 mg/kg.

PMID- 15451544
TI  - Cytotoxicity of anticancer drugs incorporated in solid lipid nanoparticles on HT
      29 colorectal cancer cell line.
AB  - Solid lipid nanoparticles (SLN) carrying cholesteryl butyrate (chol-but),
      doxorubicin and paclitaxel had previously been developed, and the
      antiproliferative effect of SLN formulations versus conventional drug
      formulations was here evaluated on HT-29 cells. The 50% inhibitory concentration
      (IC(50) values were interpolated from growth curves obtained by trypan blue
      exclusion assay. In vitro cytotoxicity of SLN carrying chol-but (IC(50 72 h) 0.3
      +/- 0.03 mM vs >0.6 mM) and doxorubicin (IC(50 72 h) 81.87 +/- 4.11 vs 126.57 +/-
      0.72 nM) was higher than that of conventional drug formulations. Intracellular
      doxorubicin was double after 24 h exposure to loaded SLN versus the conventional
      drug formulation, at the highest concentration evaluated by flow cytometry. In
      vitro cytotoxicities of paclitaxel-loaded SLN and conventional drug formulation
      (IC(50 72 h) 37.36 +/- 6.41 vs 33.43 +/-1.17 nM) were similar. Moreover, the
      combination of low concentrations of chol-but SLN (0.1-0.2 mM) and doxorubicin
      (1.72 nM) or paclitaxel (1.17 nM) exerted a greater-than-additive
      antiproliferative effect at 24 h exposure, while the combination of Na-but and
      doxorubicin or paclitaxel did not. These preliminary in vitro results suggest
      that SLN could be proposed as alternative drug delivery system.

PMID- 15451545
TI  - Delivery of all trans-retinoic acid (RA) to hepatocyte cell line from
      RA/galactosyl alpha-cyclodextrin inclusion complex.
AB  - All trans-retinoic acid (RA) plays a role in regulation of P450RAI gene
      expression. In this study, hepatocyte cell line (HepG2) was used to study an
      effect of RA released from RA/galactosyl alpha-cyclodextrin (GCD) inclusion
      complex on regulation of P450RAI gene expression. A delivery system composed of
      RA/GCD inclusion complex was applied because RA is poorly water soluble, and
      organic solvents used to dissolve it often interfere with cytotoxicity.
      Solubility of RA in water was increased by forming complex with GCD. Inclusion
      complex between GCD and RA was checked by (1)H-nuclear magnetic resonance,
      Fourier transformation infrared (FT-IR) spectroscopy and X-ray diffraction (XRD).
      The chemical shifts of the interior and exterior GCD protons in the presence of
      RA indicated that the RA was included within the GCD macrocycle cavity. The
      carbonyl band of RA and crystalline peak of RA in RA/GCD inclusion complex
      disappeared from FT-IR and XRD measurements, respectively, indication of
      inclusion complex between RA and GCD. From the observation of fluorescence
      micrograph of hepatocytes and flow cytometry measurement of HepG2, the
      internalization of fluorescein isothiocyanate-GCD by the hepatocyte occurred.
      Gene expression of P450RAI in HepG2 by delivery of RA from RA/GCD complex was
      observed.

PMID- 15451546
TI  - Influence of food on the oral bioavailability of deramciclane from film-coated
      tablet in healthy male volunteers.
AB  - The effect of a high-fat meal on the oral bioavailability of deramciclane 30 mg
      tablet was evaluated in 18 healthy male volunteers in a randomised, single dose,
      two-way crossover study. The drug was administered following an overnight fast or
      a standardised high-fat breakfast. The plasma concentrations of deramciclane and
      N-desmethylderamciclane were determined by using a validated HPLC-MS -MS/MS
      method. An effect of food on the bioavailability was indicated if the 90%
      confidence interval (CI) for the ratio of geometric means of fed and fasted
      treatments was not contained in the equivalence limit of 0.8-1.25 for AUC and
      C(max). The ratios of the mean C(max) and AUC(0-infinity) values of deramciclane
      were 1.24 (90% CI 1.12-1.38) and 1.31 (90% CI 1.21-1.41) in fed versus fasted
      subjects, which overlapped but exceeded the equivalence limit. In contrast to the
      parent compound, the 90% CI of the mean ratios for AUC(0-infinity) and C(max) of
      N-desmethylderamciclane were within the predefined range. The 24 and 31% increase
      in C(max) and AUC(0-infinity) of deramciclane, respectively, under fed condition
      is modest and probably has no clinical significance since it is relatively small
      compared to the inter-individual variability of these parameters.

PMID- 15451547
TI  - Pharmacokinetic evaluation of guar gum-based three-layer matrix tablets for oral
      controlled delivery of highly soluble metoprolol tartrate as a model drug.
AB  - The objective of the present study is to carry out pharmacokinetic evaluation of
      oral controlled release formulation (guar gum-based three-layer matrix tablets)
      containing highly soluble metoprolol tartrate as a model drug. Six healthy
      volunteers participated in the study, and a two-way crossover design was
      followed. The plasma concentration of metoprolol tartrate was estimated by
      reverse-phase HPLC. The pharmacokinetic parameters were calculated from the
      plasma concentration of metoprolol tartrate versus time data. The delayed T(max)
      lower C(max) decreased K(a) unaltered bioavailability and prolonged t(1/2)
      indicated a slow and prolonged release of metoprolol tartrate from guar gum three
      layer matrix tablets in comparison with the immediate release tablet dosage form.
      The results of the study indicated that guar gum three-layer matrix tablets were
      able to provide oral controlled delivery of highly water-soluble drug such as
      metoprolol tartrate in humans.

PMID- 15451548
TI  - Absorption characteristics of compounds with different molecular weights after
      application to the unilateral kidney surface in rats.
AB  - The aim of the present study is to clarify the absorption mechanism of a drug
      from the kidney surface membrane in rats. We studied the absorption
      characteristics of phenolsulfonphthalein (PSP) and other compounds with different
      molecular weights after their application to the rat kidney surface in vivo,
      employing a cylindrical diffusion cell (i.d. 6 mm, area 0.28 cm(2)). The time
      course of free PSP amounts remaining in the diffusion cell obeyed first-order
      kinetics at a dose of 1 mg, and its rate constant k(a) was calculated to be
      0.0137 min(-1). Absorption ratios of PSP in 4 h were calculated (from the amount
      recovered from the diffusion cell) to be 91.4, 96.4 and 97.7% at doses of 0.5, 1
      and 1.5 mg, respectively. The area under the curve for the plasma concentration
      profile of free PSP was proportional to the application dose. It is thus
      suggested that the absorption process of PSP from the rat kidney surface does not
      approach saturation at a dose of 1.5 mg. Also, no significant difference was seen
      in the k(a) values within the dose range of 0.5-1.5 mg, which were estimated by
      curve-fitting the plasma concentration profiles of free PSP in a two-compartment
      model with first-order absorption. Furthermore, we examined the importance of
      molecular weight on the absorption from the kidney surface using fluorescein
      isothiocyanate-dextrans (FDs) with molecular weights of 4400 (FD-4), 11,000 (FD
      10), 40,500 (FD-40) or 69,000 (FD-70), including the organic anions bromphenol
      blue and bromosulfonphthalein. The absorption ratios of FDs from the rat kidney
      surface in 6 h decreased with an increase in the molecular weight (76.1% for FD
      4, 54.4% for FD-10, 11.5% for FD-40 and 3.9% for FD-70). A linear relationship
      was observed between k(a) and the reciprocal value of z the square root of the
      molecular weight of these compounds. The limit of absorption from the rat kidney
      surface was extrapolated to be at a molecular weight of approximately 130,000.

PMID- 15451549
TI  - Nicotine enhancement of lipopolysaccharide/interferon-gamma-induced cytotoxicity
      with elevating nitric oxide production.
AB  - Nicotine has been shown to induce relaxation via nitric oxide (NO) production
      with activation of endothelium nitric oxide synthase (eNOS), however the effect
      of nicotine on lipopolysaccharide/interferon-gamma (LPS/IFN-gamma)-induced NO
      production and inducible NOS (iNOS) gene expression is still undefined. Here,
      nicotine alone did not affect the NO and PGE2 production in RAW264.7 and primary
      peritoneal macrophages. Interestingly, nicotine showed the dose-dependent
      stimulatory effect on LPS (20 ng/ml)/IFN-gamma (10 ng/ml)-induced NO but not PGE2
      production in both cells. Although nicotine stimulates NO production in the
      presence of LPS/IFN-gamma, LPS at the dose of 20 ng/ml, nicotine showed no
      obvious inductive effect on the expression of iNOS protein by Western blotting in
      both cells. However, nicotine significantly stimulates LPS (2.5, 5 ng/ml)/IFN
      gamma (10 ng/ml)-induced iNOS expression and NO production in RAW264.7 cells.
      Cytotoxicity assay showed that nicotine enhanced LPS (20 ng/ml) and IFN-gamma (10
      ng/ml)-induced cytotoxicity, which was inhibited by an NOS inhibitor N-nitro-L
      arginine (NLA) in RAW264.7 cells. Direct and indirect NOS activity assays
      indicated that nicotine did not affect NOS activity. And, iNOS protein stability
      was not changed by nicotine after LPS/IFN-gamma treatment. These data indicates
      that nicotine may potentiate LPS/IFN-gamma-induced cytotoxic effects by enhancing
      NO production; enhancing iNOS gene expression induced by LPS/IFN-gamma is
      involved. A cross-talk between inflammation and smoking was proposed in the
      present study.

PMID- 15451550
TI  - Protection of Ewing's sarcoma family tumor (ESFT) cell line SK-N-MC from
      betulinic acid induced apoptosis by alpha-DL-tocopherol.
AB  - Betulinic acid (BA) is known to induce apoptosis in melanoma neuroectodermal and
      malignant brain cancer cell lines. Present report describes the role of
      antioxidants on the BA-induced toxicity to human cell line SK-N-MC. Hydrophilic
      antioxidants viz., L-ascorbic acid (VitC) and N-acetyl-L-cysteine (l-NAC) had no
      protective effect on BA-induced apoptosis at the maximal concentrations tested.
      The lipophilic antioxidant, alpha-DL-tocopherol (VitE) showed a concentration and
      a time dependent effect on the protection of SK-N-MC cells from BA-induced
      apoptosis. The apoptotic parameters were analyzed using FACS analysis of
      propidium iodide (PI) stained nuclei, PS externalization using Annexin-V assay
      and changes in mitochondrial membrane potential. Generation of superoxide radical
      was monitored by the fluorescent dye hydroethidium (HE). Cells showed Annexin-V
      positivity and an increase in the propidium iodide (PI) uptake in the early hours
      of treatment with BA, which was concomitant with the loss of mitochondrial
      membrane potential. Addition of alpha-DL-tocopherol to the cell cultures 1-h
      prior to the treatment with BA abolished all the effects of BA-induced apoptosis.
      These observations suggest that BA initiates events at membrane level leading to
      induction of apoptosis. The observed ineffectiveness of hydrophilic antioxidants
      and substantial protection by lipophilic antioxidants indicate involvement of
      membrane-associated damages that form the basis of BA-induced cytotoxicity.

PMID- 15451551
TI  - Factors contributory to death of young Sprague-Dawley rats in carcinogenicity
      studies.
AB  - It is often difficult to determine the cause of early or sporadic deaths in
      toxicity studies or animal experiments. To help in the interpretation of early
      deaths, it is critical that the background incidence of factors contributory to
      death be recorded and archived. Information was collected from the control groups
      of 20 carcinogenicity studies using Sprague-Dawley (SD) rats. From a total of
      1284 males and 1264 females, 46 male (3.58%) and 44 female (3.48%) decedents were
      recorded during the first 50 weeks of study. There was no difference between the
      sexes in the probability of survival. The factors contributory to death were
      neoplastic in 17 males (37%) and 35 females (79.5%), non-neoplastic in 12 males
      (26.1%) and 3 females (6.8%) and unknown in 17 males (37%) and 6 females (13.6%).
      Of the neoplastic lesions, pituitary adenoma and mammary tumours in females were
      most common, followed by malignant lymphoma and brain tumours in both sexes. Some
      interesting and comparatively rare tumours were also seen. Death due to non
      neoplastic lesions was most often associated with lesions of the urogenital
      tract, liver and skin. A small number of animals died due to trauma or
      anaesthetic accident, or were killed because of poditis. A comparatively large
      proportion of decedents were found dead without any determinable cause of death.
      This report is intended to be of use to toxicologic pathologists in assessing
      factors contributory to death in young rats in short-term studies, and more
      especially to provide a reference to the background profiles of tumour in such
      animals.

PMID- 15451552
TI  - Evaluation of genotoxic potential of synthetic progestin chlormadinone acetate.
AB  - The genotoxicity study of a synthetic progestin chlormadinone acetate, was
      carried out on mouse bone marrow cells using sister chromatid exchanges (SCEs)
      and chromosomal aberrations (CAs) as parameter, chlormadinone acetate was studied
      at three different doses, i.e. 5.62, 11.25 and 22.50 mg/kg body weight and was
      found to be non-genotoxic at 5.62 mg/kg body weight. But at 11.25 and 22.50 mg/kg
      of body weight chlormadinone acetate increases SCE (P < 0.001) and CA (P < 0.01)
      at significant level compared to normal control. The results suggests a genotoxic
      and cytotoxic effect of chlormadinone acetate in mouse bone marrow cells.

PMID- 15451553
TI  - The effects of sub-chronic exposure of Wistar rats to the herbicide Glyphosate
      Biocarb.
AB  - The object of this study was to analyze the hepatic effects of the herbicide
      Glyphosate-Biocarb (as commercialized in Brazil) in Wistar rats. Animals were
      treated orally with water or 4.87, 48.7, or 487 mg/kg of glyphosate each 2 days,
      during 75 days. Sub-chronic treatment of animals starting from the lowest dose of
      glyphosate induced the leakage of hepatic intracellular enzymes, alanine
      aminotransferase (ALT) and aspartate aminotransferase (AST), suggesting
      irreversible damage in hepatocytes. We observed the increase of Kupffer cells in
      hepatic sinusoid of glyphosate-treated animals. This was followed by large
      deposition of reticulin fibers, composed mainly of collagen type III. We may
      conclude that Glyphosate-Biocarb may induce hepatic histological changes as well
      as AST and ALT leaking from liver to serum in experimental models.

PMID- 15451554
TI  - Investigation of circulatory and tissue ACE activity during development of lead
      induced hypertension.
AB  - Prolonged exposure to low levels of lead causes systemic hypertension. Several
      mechanisms have been proposed to explain lead-induced hypertension. Recently, the
      etiological role of the renin-angiotensin system (RAS) has been investigated in
      this context. This study assessed the alterations of circulatory and tissue
      angiotensin converting enzyme (ACE) activity during development of lead induced
      hypertension. Male rats were divided to two main groups: lead-treated animals
      which received lead acetate, 100 ppm, in drinking water for 2, 4, 6, and 8 weeks
      and a control group given distilled water. The ACE activity in serum and tissues
      was analyzed by HPLC. The blood pressure gradually increased in correlation with
      lead exposure with time. The study also revealed significant elevation of local
      and serum ACE activity in the early phase of lead treatment; however, chronic
      lead exposure suppressed ACE activity in serum and tissues. These results
      emphasize the etiological role of ACE activity in the early phase of lead-induced
      hypertension.

PMID- 15451555
TI  - Non-specific inhibition of human cytochrome P450-catalyzed reactions by hemin.
AB  - Hemin, a stable form of heme, is known to have an antimutagenic effect.
      Inhibitory effects of hemin on the cytochrome P450 (CYP)-catalyzed reactions of
      human liver microsomes and reconstituted systems containing purified CYP and
      NADPH-cytochrome P450 reductase (NPR) were seen. Hemin non-specifically inhibited
      all of the microsomal CYP activities examined. Hemin also inhibited 7
      ethoxyresorufin O-deethylation, 3-[2-(N,N-diethyl-N-methylammonium)ethyl]-7
      methoxy-4-methylcoumarin O-demethylation, and testosterone 6beta-hydroxylation
      catalyzed by purified CYPs 1A2, 2D6, and 3A4, with IC50 values of 27, 19, and 2.4
      microM, respectively. Hemin also inhibited reduction of cytochrome c and
      ferricyanide by NPR, as much as 47%. Spectrally detectable CYP was destroyed in
      human liver microsomes and in a reconstituted system in the presence of hemin and
      an NADPH-generating system. We propose that the antimutagenic effect of hemin
      might be due to inhibition of CYP and NPR enzymes involved in the bioactivation
      of mutagens.

PMID- 15451556
TI  - Methyl-paraoxon comparative inhibition kinetics for acetylcholinesterases from
      brain of neotropical fishes.
AB  - Acetylcholinesterase (AChE) sensitivity to the organophosphorus (OP) pesticide
      methyl-paraoxon was measured in fourteen species of Neotropical marine and
      freshwater fish found in the waters of Brazil. The rate constant for
      phosphorylation, kp, the dissociation constant, kd, the second order rate
      constant, ki, and the IC50 value were measured at 28 degrees C in pH 7.5 buffer
      for AChE extracted from brain. In addition, the substrate affinity constant, km,
      was measured with acetylthiocholine. The IC50 for 30 min of inhibition ranged
      from 123 nM (Prochilodus lineatus) to 3340 nM (Percophis brasiliensis), which
      corresponded to ki values of 187-6.9 mM(-1) min(-1). A 10-fold range in kp values
      from 0.21 min(-1) (Paralonchurus brasiliensis) to 2.1 min(-1) (Dules auriga) was
      associated with a 37-fold range in kd values from 4 to 150 microM. These large
      differences in reactivity with methyl-paraoxon were not reflected in the binding
      affinity for acetylthiocholine; km values were approximately 0.1-0.3 mM for all
      species. These results predict that the amino acid sequence involved in AChE
      sensitivity differs in these fishes, and that consequently some fish species may
      be resistant to the toxicity of methyl-paraoxon.

PMID- 15451557
TI  - Assessment of skin irritation and molecular responses in rat skin exposed to
      nonane, dodecane and tetradecane.
AB  - Aliphatic hydrocarbons constitute a major portion of jet fuels, kerosene and
      other solvents. This study investigated the effects of dermal exposures of
      selected aliphatic hydrocarbons (nonane, dodecane and tetradecane) on the skin
      irritation (erythema), transepidermal waterloss (TEWL) and expression of
      interleukin-1alpha (IL-1alpha), tumor necrosis factor (TNF-alpha) and monocyte
      chemoattractant protein-1 (MCP-1) in the skin and blood of hairless rats. Dermal
      exposures were carried out by occlusive application of chemicals (230 microl for
      1 h, using Hill Top Chambers) for 1 h. The expression of IL-1alpha, TNF-alpha and
      MCP-1 was measured by enzyme immunoassay (EIA), and the regulatory proteins
      NFkappaB and IkappaBalpha were measured by Western blot analysis. The skin
      irritation and TEWL data indicate that the irritation was in the following
      decreasing order: nonane > dodecane > tetradecane. Likewise, nonane significantly
      increased the expression of IL-1alpha, TNF-alpha and MCP-1 in skin and blood as
      compared to control at different time points. Dodecane and tetradecane did not
      show any increase in the expression of IL-1alpha and MCP-1 as compared to control
      (P > 0.05), but the expression of TNF-alpha by dodecane and tetradecane was
      significantly higher than control at all time points. The release of cytokines by
      nonane exposure was further supported by activation of NFkappaB p65 and
      corresponding degradation of IkappaBalpha in the skin. In conclusion, this study
      demonstrates that the biophysical parameters (TEWL and erythema scores) were
      correlated to the biomarker expressions after dermal exposures with nonane but
      not with dodecane and tetradecane. Dodecane produced only mild irritation in
      response to experimental conditions of the present study and further did not show
      significant differences in IL-1alpha and MCP-1 levels in skin and blood. However,
      TNF-alpha was well expressed in response to all the chemicals. Tetradecane did
      not show any visible signs of skin irritation and also did not produce any
      significant difference in IL-1alpha and MCP-1 release profiles as compared with
      control. The expression of TNF-alpha in skin due to tetradecane support the fact
      that visually indistinguishable skin irritation reactions can induce significant
      changes in the biological marker profile.

PMID- 15451558
TI  - Enhanced expression of human cytochrome P450 1A2 by co-expression with human
      molecular chaperone Hsp70.
AB  - Cytochrome P450 (CYP) 1A2 is of great interest because of its important roles in
      the oxidation of numerous drugs and carcinogens. Hsp70, a molecular chaperone in
      human, is known to assist the correct folding of unfolded proteins. To achieve
      high yield of recombinant human CYP1A2 in Escherichia coli, the CYP1A2 encoding
      gene was co-expressed with the chaperone Hsp70 under the control of an inducible
      tac promoter in bicistronic format. Expression level of CYP1A2 in the bicistronic
      construct reached up to 410 nmol (lculture)(-1) within 16 h at 37 degrees C,
      which is approximately 2.7-fold increase compared to the expression yield of
      CYP1A2 alone without Hsp70. The present over-expression system may be useful for
      rapid production of large amounts of active CYP1A2 in E. coli.

PMID- 15451559
TI  - Percutaneous absorption of m-xylene vapour in volunteers during pre-steady and
      steady state.
AB  - Percutaneous absorption of m-xylene (XYL) was determined in volunteers exposed to
      29.4 microg cm(-3) XYL vapour on the forearm and hand for 20, 45, 120 and 180
      min. The internal exposure was assessed by measuring the concentration of XYL in
      exhaled air. The systemic kinetics were determined using a reference exposure by
      inhalation. The dermal permeation rate and the cumulative absorption of XYL as a
      function of time were calculated using mathematical deconvolution. From these
      relationships, the average flux into the skin throughout the exposure (J(skin,
      average)) and the maximal flux into the blood (J(blood, max)) were derived. Both
      fluxes were dependent on the duration of exposure, approaching each other at
      longer exposure durations. The values of J(skin, average), adjusted to a
      concentration of 1 microg cm(-3), were 0.091 microg cm(-2) h(-1) during 20-min
      exposure falling to 0.072, 0.066 and 0.061 microg cm(-2) h(-1) for 45, 120 and
      180 min, respectively. The values of J(blood, max) showed an opposite trend,
      gradually increasing from 0.034 microg cm(-2) h(-1) at an exposure duration of 20
      min to 0.042, 0.059 and 0.063 microg cm(-2) h(-1) for 45, 120 and 180 min of
      exposure durations, respectively.

PMID- 15451560
TI  - Antimutagenicity of coriander (Coriandrum sativum) juice on the mutagenesis
      produced by plant metabolites of aromatic amines.
AB  - Aromatic amines are metabolically activated into mutagenic compounds by both
      animal and plant systems. The 4-nitro-o-phenylenediamine (NOP) is a well-known
      direct-acting mutagen whose mutagenic potential can be enhanced by plant
      metabolism; m-phenylenediamine (m-PDA) is converted to mutagenic products
      detected by the Salmonella typhimurium TA98 strain, and 2-aminofluorene (2-AF) is
      the plant-activated promutagen most extensively studied. Plant cells activate
      both 2-AF and m-PDA into potent mutagens producing DNA frameshift mutations.
      Coriander (Coriandrum sativum) is a common plant included in the Mexican diet,
      usually consumed uncooked. The antimutagenic activity of coriander juice against
      the mutagenic activity of 4-nitro-o-phenylenediamine, m-phenylenediamine and 2
      aminofluorene was investigated using the Ames reversion mutagenicity assay (his-
      to his+) with the S. typhimurium TA98 strain as indicator organism. The plant
      cell/microbe coincubation assay was used as the activating system for aromatic
      transformation and plant extract interaction. Aqueous crude coriander juice
      significantly decreased the mutagenicity of metabolized aromatic amines (AA) in
      the following order: 2-AF (92.43%) > m-PDA (87.14%) > NOP (83.21%). The
      chlorophyll content in vegetable juice was monitored and its concentration showed
      a positive correlation with the detected antimutagenic effect. Protein content
      and peroxidase activity were also determined. The concentration of coriander
      juice (50-1000 microl/coincubation flask) was neither toxic nor mutagenic. The
      similar shape of the antimutagenic response curves obtained with coriander juice
      and chlorophyllin (used as a subrogate molecule of chlorophyll) indicated that
      comparable mechanisms of mutagenic inhibition could be involved. The negative
      correlation between chlorophyll content and mutagenic response of the
      promutagenic and direct-acting used amines allows us to deduce that a chemical
      interaction takes place between the two molecules, leading to the inactivation of
      mutagenic moiety.

PMID- 15451561
TI  - Novel factors in regulation of activin signaling.
AB  - Activin type II receptors (ActRIIs) are the primary receptors that transmit the
      activin signal to intracellular signaling pathways. Binding of activins to
      ActRIIs recruits the activin type I receptor and initiates downstream signaling.
      We have found that PDZ proteins, named activin receptor-interacting proteins
      (ARIPs), specifically associate with ActRIIs. We have studied the mechanism that
      ARIPs regulate cell surface expression and cellular localization of ActRIIs.
      ARIP2 interacts with both ActRIIs and RalBP1 (Ral binding protein 1) through
      different domains to dramatically change the localization of ActRIIs.
      Overexpression of ARIP2 enhances endocytosis of ActRIIs. These data indicate that
      ARIP2 is a novel factor regulating cell surface ActRII expression and activin
      function. A novel activin binding protein, follistatin-related gene (FLRG) was
      identified. FLRG protein binds activin and myostatin with a high affinity. The
      biological activity of FLRG is similar to those of follistatin, however, the
      regulation and expression patterns of follistatin and FLRG differ.
      Immunohistochemical analysis shows that FLRG is distributed in spermatogenic
      cells of the testis, renal tubules, epithelial cells of the lung, and myocardium.
      Thus, although structurally and functionally similar, follistatin and FLRG likely
      play distinct roles as activin/GDF binding proteins in vivo.

PMID- 15451562
TI  - Beta A versus beta B: is it merely a matter of expression?
AB  - Activins are members of the transforming growth factor (TGF) beta (beta)
      superfamily of proteins that function in a wide array of physiological processes.
      Like other TGFbeta ligands, activins are biologically active as dimers. An
      activin molecule is comprised of two beta-subunits, of which four isoforms have
      been identified: betaA, betaB, betaC, and betaE. The most widely studied activins
      to date are activin A (betaA/betaA), activin B (betaB/betaB), and activin AB
      (betaA/betaB). Inhibin is a naturally occurring activin antagonist that consists
      of an alpha-subunit disulfide-linked to one of the activin beta-subunits,
      producing inhibin A (alpha/betaA), or inhibin B (alpha/betaB). The development of
      assays distinguishing between different forms of activins and inhibins, along
      with knock-in and knock-out models, have provided evidence that the betaA- and
      betaB-subunits have independent and separate roles physiologically. Additionally,
      evaluation of ligand-receptor interactions indicates significant differences in
      receptor affinity between activin isoforms, as well as between inhibin isoforms.
      In this review we explore the differences between activin/inhibin betaA- and
      betaB-subunits, including expression patterns, binding properties, and the
      specific structural aspects of each. From the growing pool of knowledge regarding
      activins and inhibins, the emerging data support the hypothesis that betaA- and
      betaB-subunits are functionally differently.

PMID- 15451563
TI  - Modulation of activin and BMP signaling.
AB  - Activins and bone morphogenetic proteins (BMPs) elicit diverse biological
      responses by signaling through two pairs of structurally related types I and II
      receptors. Here, we summarize recent advances in understanding the mode of action
      of activins and BMPs, focusing on our elucidation of the crystal structure of BMP
      7 in complex with the extracellular domain (ECD) of the activin type II receptor
      and our identification of a binding site for activin on the type I receptor ALK4.
      As a consequence of the broad range of activities of activins and BMPs, it is
      perhaps not surprising that additional mechanisms are continually being
      discovered through which a cell's responsiveness to these ligands is modulated.
      In this review, we describe novel ways in which the two extracellular cofactors,
      betaglycan and Cripto, regulate BMP and/or activin signal transduction.

PMID- 15451564
TI  - Differential actions of follistatin and follistatin-like 3.
AB  - Follistatin (FS) is an important physiological regulator of activin and other
      TGFbeta superfamily members. The recently discovered follistatin-like 3 (FSTL3;
      a.k.a. FLRG; FSRP) shares significant structural and functional homology with FS,
      but also has some interesting differences, including a prominent nuclear
      localization. The existence of these two related proteins allows detailed
      molecular and biochemical comparisons of the biologic roles of their individual
      structural elements. Current studies indicate that the heparin binding sequence
      is essential for the ability of FS to inhibit autocrine activin but is not
      sufficient to confer this activity on FSTL3. Preliminary analysis of FSTL3
      transgenic mice suggests that FSTL3 regulates gonadal development and function
      through inhibition of the paracrine activity of activin and/or other related
      factors. These studies have identified important structural elements necessary
      for biological activity of FS and FSTL3 and potential roles for FSTL3 in vivo.

PMID- 15451565
TI  - Autocrine/paracrine regulation of pituitary function by activin, inhibin and
      follistatin.
AB  - The precise regulation of the anterior pituitary is achieved by the cell-specific
      and combined actions of central, peripheral and local factors. Activins,
      inhibins, and follistatins were first discovered as gonadal factors with actions
      on FSH production from pituitary gonadotropes. With the realization that these
      factors are expressed in a wide array of tissues, including the pituitary, it
      became apparent that the functional importance of activins, inhibins, and
      follistatins extends beyond the reproductive axis and that they often exert their
      effects by autocrine/paracrine mechanisms. As members of the TGF-beta
      superfamily, activins and inhibins control and orchestrate many physiological
      processes and are vital for the development, the growth, and the functional
      integrity of most tissues, including the pituitary. Activins exert effects on
      multiple pituitary cell types but the best-characterized pituitary targets of the
      autocrine/paracrine function of activins are the gonadotropes. The
      autocrine/paracrine function of the activin-binding proteins, follistatins,
      constitutes an important local mechanism to modulate activin bioactivity while
      the restricted actions of gonadal inhibins to betaglycan-expressing gonadotropes
      provides a secondary mode of regulation of cell-specific actions of activins. The
      aim of this review is to highlight and evaluate experimental evidence that
      supports the roles of activins, inhibins, and follistatins as autocrine,
      paracrine, and/or endocrine modulators of the pituitary.

PMID- 15451566
TI  - Inhibins and adult ovarian function.
AB  - Inhibin B is predominantly produced by early healthy antral follicles during the
      luteo-follicular transition of the menstrual cycle. High inhibin B concentrations
      during the early follicular phase are responsible for the decline in FSH serum
      levels closing the FSH window and assuring single dominant follicle selection in
      the human. Early follicular phase inhibin B levels decrease over time, reflecting
      the recruitment of a diminished cohort of follicles with ovarian ageing. Hence,
      inhibin B is a predictor of poor response in IVF. In patients with PCOS inhibin B
      levels (potentially representing the number of healthy, early antral follicles)
      may be associated with the severity of ovarian dysfunction and consequently may
      predict ovulation induction outcome. However, inhibin B levels are normal in most
      PCOS patients suggesting a normal number of healthy follicles despite an increase
      in overall follicle number. Recent findings indicate that initial inhibin B
      concentrations can not predict the outcome of ovulation induction by either
      clomiphene citrate or FSH. Finally, inhibin B levels decrease over time in PCOS.

PMID- 15451567
TI  - Activin and follistatin in female reproduction.
AB  - Activin and follistatin were initially identified in the follicular fluid based
      on their effects on pituitary FSH secretion in the mid-1980s. It is now evident
      that activin, follistatin and activin receptors are widely expressed in many
      tissues where they function as autocrine/paracrine regulators of a variety of
      physiological processes including reproduction. The major function of follistatin
      is to bind to activin with high affinity and block activin binding to its
      receptors. Total activin A and follistatin are also found in the maternal
      circulation throughout pregnancy. Activin A levels are increased in abnormal
      pregnancies such as pre-eclampsia, fetal growth restriction and gestational
      hypertension. The placenta, vascular endothelial cells and activated peripheral
      mononuclear cells (PBMC) may all contribute to the raised levels of activin A in
      pre-eclampsia with unaltered follistatin in pre-eclamptic placenta, PBMCs or
      vascular endothelial cells suggesting the availability of 'free' activin A that
      could be biologically active in these cells.

PMID- 15451568
TI  - The role of activin, follistatin and inhibin in testicular physiology.
AB  - The role of the inhibins, activins and follistatins in testicular function are
      being more clearly defined following studies describing the cellular localisation
      of these proteins to the testis and the availability of specific assay systems
      enabling measurement of these proteins. Taken together with the results of
      targetted gene inactivation experiments, several concepts emerge. Inhibin B is
      predominantly produced by the Sertoli cell in many adult male mammals whereas
      there is a perinatal peak of inhibin A in the rat. In contrast, activin A has its
      highest concentrations in the immediate post-natal period during which it is
      involved in the developmental regulation of both germ cells and Sertoli cells
      being modulated by follistatin. Activin A levels are considerably lower in the
      adult testis but Sertoli cell production is stimulated by interleukin-1 and
      inhibited by FSH. Little is known about the production of activin B due to the
      absence of a suitable assay but the beta(B) subunit mRNA is expressed in germ
      cells and Sertoli cells and is stage-dependent. This pattern of expression
      suggest that it may be involved in autocrine or paracrine actions within the
      seminiferous epithelium.

PMID- 15451569
TI  - Inhibins and ovarian cancer.
AB  - The inhibins are produced and secreted by several ovarian cancers. Monitoring
      serum levels by immunoassay may be a useful diagnostic aid in the initial
      assessment of this disease and in monitoring its potential recurrence following
      surgery. The assays are applicable to women after menopause when the majority of
      ovarian cancers are detected, and when the normal ovarian production of inhibin
      is low to negligible. A new inhibin immunoassay (total inhibin ELISA) has been
      developed with the intention of widespread clinical application. The assay
      readily detects granulosa cell and mucinous tumours. CA125, a widely used ovarian
      cancer marker, detects the other main ovarian cancer types (serous, endometrioid,
      undifferentiated) with high sensitivity. The combination of the two tests detects
      the majority of ovarian cancers with high specificity (95%) and sensitivity
      (95%). Studies have been undertaken to assess its application to women in the
      perimenopausal stage and to younger women during normal reproductive life. These
      studies are providing a platform for the introduction of the test into clinical
      practice.

PMID- 15451570
TI  - Re-evaluation of inhibin alpha subunit as a tumour suppressor in prostate cancer.
AB  - Inhibin is a member of the TGF-beta superfamily of growth and differentiation
      factors and a tumor suppressor. Consistent with the tumor suppressive function of
      the inhibin alpha subunit in prostate cancer, we reported a loss of gene
      expression due to DNA hypermethylation and loss of heterozygosity (LOH) as well
      as down regulation of inhibin alpha subunit immunoreactivity. Paradoxically, an
      expanded study to evaluate the prognostic significance of inhibin alpha subunit
      expression in men with prostate cancer resulted in a contradictory outcome,
      whereby an up-regulation of subunit expression was recorded. In seeking a more
      comprehensive explanation for all data sets, we offer a unifying hypothesis. We
      propose that the tumor suppressor activities of the inhibin alpha subunit
      dominate in non-malignant tissue, but its oncogenic activities emerge during
      tumorigenesis. An explanation such as this, involving a switch in gene function
      from being tumor suppressive to pro-oncogenic, may account for the discrepant
      findings in other types of cancer.

PMID- 15451571
TI  - Activin, inhibin and the human breast.
AB  - Activins and inhibins are growth factors involved in cell differentiation and
      proliferation. Human breast tissues such as normal mammary tissue, fibroadenoma,
      and breast cancer express inhibin and activin mRNA and proteins. Activin A and
      its binding protein, follistatin, are also present in human milk during the first
      week of lactation. Using immunohistochemistry, we have observed that the
      inhibin/activin alpha, betaA, and betaB subunits are present in normal breast
      tissue regardless of menstrual cycle phase or menopause, as well as in
      fibrocystic disease, and breast tumors. The mRNAs encoding all three
      activin/inhibin subunits are expressed in breast carcinoma, fibroadenoma, and
      normal mammary tissue. The betaA subunit gene expression is higher in either
      local or metastatic breast carcinoma than in normal tissue. In addition, dimeric
      activin A is detectable in homogenates of breast cancer tissue at concentrations
      twice as high as in non-neoplastic adjoining tissue. Recent evidence suggests
      that some of the activin A produced by breast carcinoma is released into systemic
      circulation. In women with breast cancer, serum activin A levels are often
      elevated, and a significant decrease is observed in the first and second days
      following tumor excision. The role of activin and inhibin as endocrine and/or
      paracrine factors in the breast is still uncertain. Activin has complex effects
      on cell growth during branching morphogenesis, but it is generally considered as
      an inhibitor of cell proliferation as in vitro studies have shown that activin A
      treatment of breast cancer cells arrests cell growth. Inhibin is generally
      considered as a tumor suppressor, but its possible role in the breast is less
      understood.

PMID- 15451572
TI  - Genetic models for transforming growth factor beta superfamily signaling in
      ovarian follicle development.
AB  - The transforming growth factor beta (TGFbeta) superfamily has wide-ranging and
      profound effects on many aspects of cellular growth and development. Many TGFbeta
      related ligands, receptors, and intracellular signaling proteins are expressed in
      the ovary and are critical for normal follicle development. Our laboratory and
      others have analyzed the in vivo function of the TGFbeta superfamily signal
      transduction pathways by using gene knockout and knockin approaches. Two TGFbeta
      superfamily ligands, growth differentiation factor 9 (GDF9) and bone
      morphogenetic protein 15 (BMP15), are expressed in developing oocytes. Based on
      in vivo data using knockout models, GDF9 is critical at both the primary and
      preovulatory stages of follicle development, and physiologically interacts with
      BMP15 during the latter stages of folliculogenesis. A knockin model of activin
      betaB expressed from the activin betaA locus, revealed that activin betaB can act
      as a hypomorphic protein and rescue some but not all of activin betaAs functions.
      Questions of functional redundancy of signaling components and multiple receptor
      utilization by different ligands still need to be addressed for these pathways.
      Answers will likely come from using existing single null mouse models to generate
      combinatorial ligand and receptor null mice. These new models may reveal the in
      vivo genetic interactions of TGFbeta superfamily ligands, receptors, binding
      proteins, and downstream signaling pathways.

PMID- 15451573
TI  - Inhibins and activins in pregnancy.
AB  - Human placenta, decidua, and fetal membranes are the major sites of production
      and secretion of inhibin A and activin A in maternal serum, amniotic fluid, and
      umbilical cord blood. These tissues also express follistatin-related gene and
      betaglycan, the binding proteins of activin A and inhibin A, respectively,
      recently identified. They show a different expression throughout pregnancy,
      suggesting new functional roles into gestational tissues. The availability of
      suitable assays for measuring inhibin A and activin A lead us the possibility to
      investigate their secretion in healthy pregnancy. In addition, several evidences
      underline the potential role and the clinical usefulness of their measurement in
      the diagnosis, prevention, prognosis and follow-up of different gestational
      pathologies such as: threatened abortion, placental tumors, hypertensive
      disorders of pregnancy, intrauterine growth restriction, fetal hypoxia. The
      measurement of inhibin A and activin A into the biological fluids of pregnancy
      will offer in the future further possibilities in early diagnosis, prediction,
      and monitoring pregnancy diseases.

PMID- 15451574
TI  - Inhibins and activins in human fetal abnormalities.
AB  - To date, the only routine clinical application of inhibin or activin measurement
      in testing for fetal abnormalities has been the use of inhibin A in prenatal
      screening for trisomy 21 (Down syndrome). Second trimester maternal serum levels
      of inhibin A are, on average, two-fold higher in Down syndrome than in unaffected
      pregnancies. Although the biology of altered second trimester maternal serum
      analyte levels in Down syndrome pregnancy cannot yet be explained, it seems that
      fetal products tend to be decreased, while placental products tend to be
      increased. This pattern holds true for inhibin A because maternal serum levels
      appear to be derived from placental rather than fetal sources. Therefore, the
      measurement of inhibins and activins in maternal fluids, although clinically
      useful and relatively easy to obtain, may not be helpful in studying their role
      in human fetal development. Studies in transgenic mice indicate a role for
      activin, follistatin, and activin receptor type IIA in development of the palate
      and craniofacial region. Cleft palate is a common birth defect and is associated
      with serious feeding and respiratory complications in newborns. We have begun to
      investigate the potential role of activin in human craniofacial development by
      examining the spatial and temporal expression of inhibin/activin subunits,
      follistatin and the activin receptors in the fetal palate. Palate tissues were
      collected at autopsy from fetuses ranging in gestational age from 9 to 42 weeks,
      and 8 week embryonic tissues were also examined. Tissues were either stored in
      paraffin for immunocytochemistry or were frozen for RT-PCR examination of the
      expression of inhibin/activin proteins or mRNAs, respectively. To date, betaA
      subunit, follistatin, and activin receptor, but not alpha and betaB subunit,
      mRNAs are present in palate tissues and inhibin/activin betaA immunoreactivity
      has been consistently observed in developing bone. Expression of the activin A
      subunit and its receptors in the human fetal palate are consistent with a
      developmental role. Studies are ongoing to determine whether altered activin
      biosynthesis is associated with cleft palate. Future studies of fetal tissues may
      help to elucidate other roles for the TGF-beta family in human development.

PMID- 15451575
TI  - FLRG, member of the follistatin family, a new player in hematopoiesis.
AB  - Several years ago, we cloned and characterized from a B cell leukemia a new
      secreted protein which, on the basis of its high degree of structural homology
      with follistatin, was defined as a member of the follistatin family and
      accordingly named follistatin-related gene (FLRG). However, follistatin and FLRG
      revealed non-overlapping patterns of expression in various tissues thereby
      indicating the existence of non-redundant functional roles for these proteins
      throughout the organism. As known for a long time, follistatin is a biological
      regulator of activin and bone morphogenetic protein (BMP) function in various
      cellular systems: in particular, it inhibits the effects of activin on
      hematopoiesis. We therefore investigated the expression and effects of FLRG
      during human hematopoiesis with particular focus on the effect of this soluble
      glycoprotein in the regulation of erythropoiesis. For this purpose, we have for
      the first time, compared the role of Activin A, BMP2 and BMP4 during
      erythropoiesis, in primary human cells. Our results indicate that, BMP2 acts on
      early erythroid cells while Activin A acts on a more differentiated population.
      We report the induction by Activin A and BMP2 of cell commitment towards
      erythropoiesis in the absence of EPO. This induction involves two key events:
      increase of EPO-R and the decrease of GATA2 expression. Our results indicate that
      despite their high structural homology, follistatin and FLRG do not regulate the
      same signaling targets, therefore highlighting distinct functions and mechanisms
      for these two proteins in the human hematopoietic system. We thus propose a
      working model for the regulation of activin or BMP-induced human erythropoiesis
      by follistatin/FLRG.

PMID- 15451576
TI  - Activin A and follistatin in systemic inflammation.
AB  - Inflammation is a complex process regulated by a cascade of cytokines and growth
      factors. This review summarizes the emerging evidence implicating activin A and
      follistatin in the inflammatory process. Our recent studies have highlighted that
      activin A is released early in the process as part of the circulatory cytokine
      cascade during acute systemic inflammation. This release occurs concurrently with
      tumor necrosis factor (TNF)-alpha and prior to that of interleukin (IL)-6 and
      follistatin. Although, the cellular source(s) of activin A are yet to be
      established, circulating blood cells and the vascular endothelium are candidates
      for this rapid release of activin A into the circulation. The release of activin
      A and follistatin is also observed in the clinical setting, in particular in
      sepsis. Furthermore activin A is released into cerebrospinal fluid in a model of
      meningitis in rabbits. The role of activin A in the inflammatory response is
      poorly understood, however, in vitro data has highlighted that activin A can have
      both pro- and anti-inflammatory actions on key mediators of the inflammatory
      response such as TNF-alpha, IL-1beta and IL-6. Furthermore, emerging data would
      suggest that activin A induction is restricted to certain types of inflammation
      and its release is dependant upon the inflammatory setting.

PMID- 15451577
TI  - Activin: an important regulator of wound repair, fibrosis, and neuroprotection.
AB  - We recently identified the gene encoding the activin betaA chain as a novel
      injury-regulated gene. We showed that activin over-expression in the skin of
      transgenic mice enhances the speed of wound healing but also the scarring
      response. By contrast, inhibition of activin action by over-expression of the
      activin antagonist follistatin caused a severe delay in wound repair, but the
      quality of the healed wound was improved. In a search for activin-regulated genes
      in keratinocytes we identified the Mad1 transcription factor as a direct target
      of activin in these cells. Since Mad1 inhibits proliferation and induces
      differentiation of various cell types, our results suggest that activin regulates
      these processes in keratinocytes via induction of mad1. In addition to its role
      in the skin, we recently identified activin as a novel neuroprotective factor in
      vivo. Together with results from other laboratories, these findings suggest that
      activin is an important player in inflammation, repair and cytoprotection in
      various organs.

PMID- 15451578
TI  - Proceedings of the International Workshop on Inhibins, Activins and Follistatins.
      Siena, Italy, July 3-4, 2003.

PMID- 15451579
TI  - Arthur Guedel and the oropharyngeal airway.

PMID- 15451580
TI  - International EMS systems: France.
AB  - The EMS (Emergency Medical Service) system in France is a centrally based, two
      tiered, physician-manned system. The first level is composed of BLS (Basic Life
      Support) fire department ambulances (called "VSAB") based at fire stations. The
      second level is composed of ALS (Advanced Life Support) physician staffed
      ambulances. In France, there are two different levels of emergency department
      (ED). The first level is called "SAU" and has continuous coverage by surgeons, in
      Level 2 certain specialities may be available only on an "on-call" basis.
      Staffing patterns in the ED vary from one hospital to another. In general, EDs in
      university and major teaching hospitals are staffed by emergency physicians and
      residents from different specialties. In France medical schools are part of free
      public universities. The length of medical training varies from 8 to 11 years
      according to speciality. Emergency Medicine is not recognised as a stand alone
      specialty.

PMID- 15451581
TI  - Preliminary in-hospital experience with a fully automatic external cardioverter
      defibrillator.
AB  - BACKGROUND: Ventricular fibrillation (VF) and ventricular tachycardia (VT) are
      frequently present as initial rhythms during in-hospital cardiac arrest. Although
      ample evidence exists to support the need for rapid defibrillation, the response
      to in-hospital cardiac arrest remains without major advances in recent years. The
      delay between the arrhythmic event and intervention is still a challenge for
      clinical practice. OBJECTIVE: To analyze the performance and safety of in
      hospital use of a programmable, fully automatic external cardioverter
      defibrillator (AECD). METHODS: We conducted a prospective study at the Emergency
      Department of a university hospital. A total of 55 patients considered to be at
      risk of sustained VT/VF were included. Patients underwent monitoring of their
      cardiac rhythm by the AECD. Upon detection of a ventricular tachyarrhythmia, the
      AECD was programmed to automatically deliver shock therapy. RESULTS: We recorded
      19 episodes of VT/VF in 3 patients. The median time between the beginning of the
      arrhythmia and the first defibrillation was 33.4 s (21-65 s). One episode of
      spontaneous reversion of VT was documented 20 s after its origin and shock
      therapy was aborted. The defibrillation success was 94.4% (17/18) for the first
      shock and 100% (1/1) for the second shock. No case of inappropriate shock
      discharge was registered during the study period. CONCLUSION: The AECD has the
      feasibility to combine long-term monitoring with automatic defibrillation safely
      and effectively. It presents the possibility of providing rapid identification
      of, and response to, in-hospital ventricular tachyarrhythmias.

PMID- 15451582
TI  - Incidence of EMS-treated out-of-hospital cardiac arrest in the United States.
AB  - BACKGROUND: The potential impact of efforts to improve the chain of survival for
      out-of-hospital sudden cardiac arrest (SCA) is unclear in part because estimates
      of the incidence of treatable cases of SCA are uncertain. The aim of the
      investigation was to determine a representative national incidence of emergency
      medical services (EMS)-treated all-rhythm and ventricular fibrillation (VF) SCA
      as well as survival. METHODS: We used Medline to identify peer-reviewed articles
      published between 1 January 1980 and 31 March 2003 that reported a US community's
      EMS SCA experience. Inclusion criteria required the study to include at least 25
      cases, report the total number of all-rhythm and/or ventricular fibrillation
      arrests, and provide information about population size and study duration.
      Incidence was computed by dividing the total number of SCA events by the product
      of the community's population and the study duration. RESULTS: Reports from 35
      communities met the inclusion criteria. A total of 35,801 all-rhythm EMS-treated
      cardiac arrests occurred during 62.11 million person-years of observation
      resulting in an overall incidence of 54.99 per 100,000 person-years. The
      incidence of ventricular fibrillation-rhythm SCA was 21.32 per 100,000 person
      years. Sensitivity analyses generally produced similar results. Applying these
      results to the US population, 155,000 persons would experience EMS-treated all
      rhythm SCA and 60,000 persons would experience EMS-treated ventricular
      fibrillation-rhythm SCA annually in the US. Survival was 8.4% for all-rhythm and
      17.7% for ventricular fibrillation SCA. CONCLUSION: The results provide a
      framework to assess opportunities and limitations of EMS care with regard to the
      public health burden of SCA.

PMID- 15451583
TI  - In-water resuscitation--is it worthwhile?
AB  - OBJECTIVES: At present, there is no reliable information indicating the best
      option of rescuing a non-breathing drowning victim in the water. Our objectives
      were to compare the outcomes of performing immediate in-water resuscitation (IWR)
      or delaying resuscitation until the victim is brought to shore. MATERIAL AND
      METHODS: A retrospective data analysis was conducted of non-breathing drowning
      victims rescued by lifeguards in the coastal area of Rio de Janeiro, Brazil.
      Patients were coded as IWR and no-IWR (NIWR) cases based on the lifeguard's
      decision whether to perform IWR. Death and development of severe neurological
      damage (SND) were considered poor outcome. RESULTS: Forty-six patients were
      studied. Their median age was 17 (9-31) years. Nineteen (41.3%) patients received
      IWR and 27 (58.7%) did not. The mortality rate was lower for IWR cases (15.8%
      versus 85.2%, P < 0.001). However, among surviving IWR cases, 6 (31.6%) developed
      SND. In multivariate analysis, higher age [odds ratio (OR) = 1.12 (95% confidence
      interval (CI) = 1.01-1.24), P = 0.038] was associated with death, while IWR [ OR
      = 0.05 (95% CI = 0.01-0.50), P = 0.011] was protective. When death or the
      development of SND was set as the dependent variable, longer cardiopulmonary
      arrest (CPA) duration was the unique variable selected (OR = 1.77 (95% CI = 1.13
      2.79), P = 0.013]. Every patient with CPA duration higher than 14 min had a poor
      outcome. CONCLUSIONS: Delaying resuscitation efforts were associated with a worse
      outcome for non-breathing drowning victims. In the cases studied, IWR was
      associated with improvement of the likelihood of survival. An algorithm was
      developed for its indications and to avoid unnecessary risks to both victim and
      rescuer.

PMID- 15451584
TI  - Training of police officers as first responders with an automated external
      defibrillator.
AB  - A short and effective training programme is an essential prerequisite for the use
      of automated external defibrillators (AED) by EMS providers and first responders.
      We evaluated a 3-h AED course based on the ERC requirements. METHODS: As part of
      a study evaluating the effectiveness of AEDs used by first responders (ARREST 4),
      we trained all police officers in the region of Amsterdam, the Netherlands. By
      means of a Basic Life Support (BLS) assessment at the beginning of the course and
      at the end, we evaluated whether BLS can be improved in a 3-h AED course. Through
      a combined BLS and AED assessment at the end of the course, we evaluated whether
      AED skills can be acquired sufficiently. BLS skills were measured with the
      Laerdal SkillMeter in evaluation mode. AED skills were assessed using 13
      criteria. By means of logistic regression, we analysed the influence of student
      characteristics, such as age, gender, previous training, resuscitation experience
      and motivation for BLS and AED on BLS and AED skills acquisition. RESULTS:
      Between September 1999 and June 2000, 823 police officers were trained (76% male,
      mean age 36 (S.D. 9) years). BLS improved significantly (P < 0.001) in all
      criteria, except for hypoventilation (P < 0.001). After training, 89% of the
      students were able to use an AED safely and effectively. Self-confidence and
      motivation improved from 12 and 73% to 99 and 94% over the course (P < 0.001).
      Independent student characteristics influencing the success of the AED course
      were: previous BLS training, motivation before the course for an AED, and
      resuscitation experience that dated back for more than 12 months. CONCLUSION: The
      majority of police officers can be trained to use an AED safely and effectively
      within a 3-h AED course. During this course, they also improve on their BLS
      skills. Successful completion of the course depends in part on the student
      characteristics.

PMID- 15451585
TI  - Automated external defibrillation by untrained deaf lay rescuers.
AB  - INTRODUCTION: The use of automated external defibrillators (AEDs) by lay rescuers
      can reduce the time to defibrillation, improving survival after out-of-hospital
      cardiac arrest. However, some people have hearing defects that can prevent them
      from understanding the AED verbal prompts. Moreover, even rescuers with normal
      hearing function may not easily understand the AED verbal prompts when operating
      in a noisy environment. This study was designed to assess the capability of
      rescuers to defibrillate effectively using an AED which included visual prompts.
      METHODS AND RESULTS: Nine deaf employees with no previous experience in basic
      life support (BLS) or defibrillation were asked to defibrillate a manikin
      following the text prompts of a Heartstart FR2+ AED. Subjects were tested before
      and after a 6 h BLS-AED course carried out with the help of a sign language
      interpreter. Before training, seven out of nine deaf subjects (78%) were able to
      defibrillate, eight out of nine subjects (89%) placed the pads correctly, and the
      mean time to defibrillation was 101.3 +/- 28.4 s. After the course, all subjects
      were able to complete the defibrillation sequence and place the pads correctly.
      The mean post-course time to defibrillation was 47.8 +/- 5.4 s (P < 0.001). None
      of the nine subjects touched the manikin during charging of the defibrillator and
      shock delivery before or after the course. CONCLUSIONS: This study demonstrates
      that untrained deaf rescuers can use AEDs appropriately providing that the
      defibrillator has visual instructions. Training improves defibrillator use and
      reduces time to defibrillation.

PMID- 15451586
TI  - Long-term prognosis after out-of-hospital cardiac arrest and primary percutaneous
      coronary intervention.
AB  - AIMS: To study the long-term survival after out-of-hospital cardiac arrest and
      successful cardiopulmonary resuscitation (CPR) in patients with acute ST-segment
      elevation myocardial infarction (STEMI) treated with primary percutaneous
      coronary intervention (PCI). MATERIAL AND METHODS: In-hospital and 2-year
      survival of 40 patients treated with primary PCI after out-of-hospital cardiac
      arrest and STEMI was compared with that of a reference group of 325 STEMI
      patients, without cardiac arrest, also treated with primary PCI in the same
      period. RESULTS: In the group with out-of-hospital cardiac arrest, both in
      hospital and 2-year mortality was 27.5%. In the reference group, in-hospital and
      2-year mortality was 4.9 and 7.1%, respectively. After discharge from hospital
      there was no significant difference in mortality between the groups. CONCLUSION:
      Long-term prognosis is good in selected patients after successful out-of-hospital
      CPR and STEMI treated with primary PCI.

PMID- 15451587
TI  - Brain arrest neurological outcome scale (BrANOS): predicting mortality and severe
      disability following cardiac arrest.
AB  - BACKGROUND: To create a predictive scale of neurological outcome following
      cardiac arrest (CA) that incorporates radiological and clinical markers of brain
      injury. METHODS AND RESULTS: Brain arrest neurologic outcome scale (BrANOS) is a
      prospective 16-point scale. It consisted of three variables: (1) duration of
      arrest (DAR), (2) reversed Glasgow coma scale (GCS), and (3) Hounsfield unit (HU)
      ratio on non-contrast CT scan of the head. Reversed GCS score was defined as 15
      GCS (best GCS in the first 24 h). HU ratio was defined as the density ratio of
      the caudate nucleus over the posterior limb of the internal capsule measured on
      unenhanced CT scan of the brain. We identified 32 comatose patients who had: (1)
      CT scan performed within 48 h of event; (2) no previous history of either coma,
      severe head trauma, cardiac arrest or stroke. Primary outcome was defined as
      alive or dead. Secondary outcome was the Glasgow outcome score recorded on
      discharge. Patient demographics were collated from retrospective chart review.
      Patients' mean age was 63 +/- 3 years (mean +/- S.E.M.); 44% were females.
      Mortality rate was 81%. Mean DAR was 21 +/- 2 min. Survivors had a significantly
      lower BrANOS score (8 +/- 2 points) compared to non-survivors (13 +/- 1) (P =
      0.006). BrANOS was a strong predictor of mortality alone (ROC = 0.86) and
      mortality with severe disability combined (ROC = 0.9). The scale had a 100%
      specificity and positive predictive value. CONCLUSIONS: BrANOS is a reliable
      predictor of neurological outcome following CA. It is the first scale to
      incorporate clinical and radiological markers of brain injury.

PMID- 15451588
TI  - Electrical therapy for post defibrillatory pulseless electrical activity.
AB  - BACKGROUND: Defibrillation may convert ventricular fibrillation (VF) only to
      reveal profound mechanical dysfunction. Survival following this dysfunction,
      known as pulseless electrical activity (PEA) and electromechanical dissociation
      (EMD), is uncommon. We sought to evaluate an electrical therapy for primary post
      shock PEA following short duration VF. METHODS AND RESULTS: Forty-eight episodes
      of VF, lasting 110 +/- 25 s, were induced in 16 anesthetized dogs. Following
      defibrillation, 35 episodes met PEA criteria (ABP < or = 36 mmHg diastolic and
      pulse pressure < or = 14 mmHg in the first 20 s post shock). These post
      defibrillation PEA episodes were either Not Treated (NT) or Treated (T) with
      packets of 4-20 monophasic 0.2 ms 50-100 Hz pulses of 20-60 V applied across the
      tip and coil of an integrated bipolar transvenous defibrillation lead positioned
      in the right ventricle. The therapeutic endpoint was return of spontaneous
      circulation (ROSC; self-sustained ABP > or = 60 mmHg diastolic and/or > or = 100
      mmHg systolic) for over 2 min. In the Not Treated group, only 4 of 19 (21%)
      episodes spontaneously recovered to ROSC in 123 +/- 49 s while in the Treated
      group, 11 of 16 (69%) of the PEA episodes achieved ROSC in 102 +/- 92 s.
      CONCLUSIONS: Electrical therapy increased the likelihood of ROSC in primary post
      defibrillation PEA three-fold (P < 0.01). Recovery occurred in the absence of
      thoracic compression, mechanical ventilation, or adjunctive drug therapy.

PMID- 15451589
TI  - Effects of hypertonic versus isotonic infusion therapy on regional cerebral blood
      flow after experimental cardiac arrest cardiopulmonary resuscitation in pigs.
AB  - OBJECTIVE: To evaluate the effects of hypertonic, isooncotic, and isotonic
      infusion therapy on cerebral blood flow (CBF) during and after cardiopulmonary
      resuscitation (CPR) from experimental cardiac arrest (CA). METHODS: In 32
      domestic swine (13-23 kg) open chest CPR was initiated after 8 min of ventricular
      fibrillation. With the onset of CPR animals randomly received 2 ml/kg per 10 min
      of either hypertonic saline (HS: 7.2% NaCl), hypertonic-isooncotic HES-saline
      (HHS: 7.2% NaCl in 6% HES 200,000/0.5), isooncotic HES (6% HES 200,000/0.5), or
      isotonic (normal) saline (NS: 0.9% NaCl). Haemodynamic variables were monitored
      continuously, and coloured microspheres were used to measure CBF quantitatively
      before CA, during CPR, and 20, 90 and 240 min after restoration of spontaneous
      circulation (ROSC). RESULTS: In HES/NaCl treated animals, CBF significantly
      decreased during CPR compared to the prearrest level (P < 0.01, respectively;
      MANOVA). In contrast, CBF was sustained during CPR in HS/HHS treated animals and
      significantly higher compared to animals receiving NS (P < 0.05, respectively).
      During recirculation severe postischaemic hypoperfusion as indicated by a
      decrease of CBF below the prearrest level, was present only in animals receiving
      HES and NS. CONCLUSIONS: Hypertonic solutions (HS/HHS) applied during internal
      cardiac massage enhanced CBF during CPR and after ROSC.

PMID- 15451590
TI  - Ventricular fibrillation frequency characteristics and time evolution in piglets:
      a developmental study.
AB  - BACKGROUND: Derived variables of ventricular fibrillation, such as the frequency
      distribution by fast Fourier transformation and its evolution over time, have
      been used to determine the optimum timing for defibrillation. We hypothesized
      that these frequency variables would differ among neonatal, young child and older
      child populations due to cardiac developmental and size differences. Such
      differences may have important implications for developing defibrillation
      algorithms for pediatric patients and for extrapolating adult defibrillation
      algorithms to children in VF. METHODS: Ventricular fibrillation was induced and
      recorded for 6 min in 4 kg (n = 11), 14 kg (n = 10), and 24 kg (n = 16) piglets,
      corresponding to neonatal, young child and older children. Mean, median, and
      dominant frequencies were computed in 30 s intervals and compared among weight
      classes. RESULTS: All frequency variables in all weight groups showed first a
      decline at 1.25-1.75 min, followed by a gradual rise and plateau. There were
      significant differences for mean, median and dominant frequencies among weight
      classes. Specifically, 14 kg piglets showed higher frequency variables overall
      with a time evolution that was different from that of 4 and 24 kg piglets. Mean
      frequency showed the most stable time evolution with the least moment-to-moment
      variability. CONCLUSION: The frequency waveform characteristics and time course
      are somewhat different in 14 kg piglets compared with 4 and 24 kg piglets. If
      similar differences are demonstrable among children of different weights and
      ages, AEDs designed to determine optimal timing of defibrillation shocks in
      adults by frequency waveform characteristics may require modification for use in
      children with VF.

PMID- 15451591
TI  - Sudden death caused by dissecting thoracic aortic aneurysm in a patient with
      autosomal dominant polycystic kidney disease.
AB  - Among the fatal vascular complications associated with autosomal dominant
      polycystic disease (ADPKD), ruptured intracerebral aneurysm and ruptured
      abdominal aortic aneurysm are widely known. However, there are few reports on the
      dissecting thoracic aortic aneurysm as a fatal complication of ADPKD. We report a
      case of a 58-year-old man with a history of ADPKD who presented to the emergency
      department with out-of-hospital cardiac arrest. Immediate cardiopulmonary
      resuscitation restored a spontaneous circulation successfully and subsequent
      image study revealed a type I dissecting thoracic aortic aneurysm. Emergency
      aortic grafting was performed--but he died from postoperative haemorrhage. The
      surgical specimen of the aorta showed cystic medial necrosis. This rare case
      emphasizes the need to consider such a diagnosis in a patient with ADPKD who
      presents to the emergency department with sudden cardiac arrest. In addition, the
      histological finding indicates the aetiological role of a collagen defect in
      addition to chronic hypertension in the pathogenesis of aortic dissection in
      ADPKD patients.

PMID- 15451592
TI  - Posterior tracheal wall laceration after blunt neck trauma in children: a case
      report and review of the literature.
AB  - Adults seem to be more vulnerable than children to tracheal lacerations. Tracheal
      lacerations have been described particularly after surgical procedures and
      penetrating trauma, but they may also result from minor blunt trauma. We report
      the case of a 7-year-old boy who sustained a posterior tracheal wall laceration
      after a direct frontal fall on a wooden strut. We also review the literature on
      posterior wall tracheal laceration as an isolated feature after blunt cervical
      trauma in children, the diagnostic features and management options.

PMID- 15451593
TI  - Childhood and malaria vaccines combined in biodegradable microspheres produce
      immunity with synergistic interactions.
AB  - Biodegradable microspheres may represent a potential tool for the delivery of
      combination vaccines. We demonstrate strong immunogenicity of five co
      encapsulated antigens after a single subcutaneous inoculation in guinea pigs.
      Tetanus- and diphtheria-specific antibodies were not significantly affected by
      the presence of either antigen or by the presence of pertussis or Haemophilus
      influenzae type b (Hib) antigens. Microsphere formulations gave better protection
      against diphtheria toxin than did two injections of a licensed tetravalent
      vaccine. Finally, a synthetic malaria peptide antigen (PfCS) also encapsulated in
      PLGA microspheres increased diphtheria and tetanus-specific immunity and improved
      protection against diphtheria. These findings demonstrate the potential of
      microspheres as an alternative and promising strategy for combination vaccines
      with a further aptitude in reducing the number of inoculations required to gain
      functional immunity.

PMID- 15451594
TI  - Aerosolization properties, surface composition and physical state of spray-dried
      protein powders.
AB  - Powder aerosols made of albumin, dipalmitoylphosphatidylcholine (DPPC) and a
      protein stabilizer (lactose, trehalose or mannitol) were prepared by spray-drying
      and analyzed for aerodynamic behavior, surface composition and physical state.
      The powders exited a Spinhaler inhaler as particle aggregates, the size of which
      depending on composition, spray-drying parameters and airflow rate. However, due
      to low bulk powder tap density (<0.15 g/cm3), the aerodynamic size of a large
      fraction of aggregates remained respirable (<5 microm). Fine particle fractions
      ranged between 21% and 41% in an Andersen cascade impactor operated at 28.3
      l/min, with mannitol and lactose providing the most cohesive and free-flowing
      powders, respectively. Particle surface analysis by X-ray photoelectron
      spectroscopy (XPS) revealed a surface enrichment with DPPC relative to albumin
      for powders prepared under certain spray-drying conditions. DPPC self-organized
      in a gel phase in the particle and no sugar or mannitol crystals were detected by
      X-ray diffraction. Water sorption isotherms showed that albumin protected lactose
      from moisture-induced crystallization. In conclusion, a proper combination of
      composition and spray-drying parameters allowed to obtain dry powders with
      elevated fine particle fractions (FPFs) and a physical environment favorable to
      protein stability.

PMID- 15451595
TI  - Radiation-guided drug delivery to tumor blood vessels results in improved tumor
      growth delay.
AB  - Tumor blood vessels are biological targets for cancer therapy. In this study, a
      tumor vasculature targeting system that consisted of liposomes and lectin (WGA)
      was built. Liposomes were used to carry a number of liposome-friendly anti
      tumoral agents along with WGA, a lectin which posseses a specific affinity for
      binding to inflamed endothelial cells. In order to target tumor vasculature,
      inflammation of endothelial cells was induced by radiation. Because ionizing
      radiation induces an inflammatory response in tumor vasculature, lectin
      conjugates were utilized to determine whether radiation can be used to target
      drug delivery to tumor vessels. Wheat germ agglutinin (WGA) is one such lectin
      that binds to inflamed microvasculature. WGA was conjugated to liposomes
      containing cisplatin and administered to tumor bearing mice. Tumor growth delay
      was used to analyze the efficacy of cytotoxicity. FITC-conjugated WGA accumulated
      within irradiated tumor microvasculature. WGA was conjugated to liposomes and
      labeled with 111In. This demonstrated radiation-inducible tumor-selective
      binding. WGA-liposome-conjugates were loaded with Cisplatin and administered to
      mice bearing irradiated tumors. Tumors treated with a combination of liposome
      encapsulated cisplatin together with radiation showed a significant increase in
      tumor growth delay as compared to radiation alone. These findings demonstrate
      that ionizing radiation can be used to guide drug delivery to tumor
      microvasculature.

PMID- 15451596
TI  - WGA-grafted PLGA-nanospheres: preparation and association with Caco-2 single
      cells.
AB  - Biotech drugs are poorly absorbed, highly susceptible to loss of activity, and
      require formulations with protective effects. Their incorporation into
      nanospheres is a promising approach since colloidal formulations were shown to be
      absorbed. Due to rather low absorption rates the surface engineering with
      absorption enhancing agents is a current challenge. Thus, an optimized protocol
      relying on carbodiimide-mediated covalent binding of biorecognitive ligands to
      the surface of biodegradable and biocompatible poly(D,L-lactic-co-glycolic)acid
      (PLGA) nanospheres was established. Important parameters such as retainment of
      particle size distribution and biorecognitive characteristics of the ligand as
      well as storage stability were considered. As exemplified by nanoparticles
      grafted with wheat germ agglutinin (WGA) as a carbohydrate binding ligand and
      Caco-2 single cells, flow cytometry as well as confocal laser scanning microscopy
      revealed improved cytoassociation of the nanoscaled carriers as compared to the
      unmodified ones. As detected by flow cytometry, the binding of WGA-decorated
      nanospheres considerably increases the roughness of the cell surface with
      increasing ligand density. Additionally, the biorecognitive nanoparticles were
      not toxic in the Caco-2 model. The protocol presented for surface modification of
      nanospheres promises high versatility of application in search for biorecognitive
      ligands enhancing the cytoadhesion, cytoinvasion as well as transcellular
      transport of colloidal carriers.

PMID- 15451597
TI  - Cyclodextrin enhanced transdermal delivery of piroxicam and carboxyfluorescein by
      electroporation.
AB  - The transdermal transport of cyclodextrins (CD) across porcine epidermis by
      electroporation was studied. Electroporation increased the permeation of beta
      cyclodextrin (BCD) and hydroxy propyl beta-cyclodextrin (HPCD) by several orders
      of magnitude, relative to passive transport. The presence of BCD and HPCD
      enhanced the total transport of the test permeants piroxicam and
      carboxyfluorescein (CF), respectively, from both permeant solutions and
      suspensions. BCD enhanced the fraction of piroxicam transported across the
      epidermis into the receiver compartment medium. This was most likely due to the
      prolonged post-pulse permeability state of the epidermis. The fraction of CF
      retained in the epidermis was increased by HPCD. The rate of diffusion of CF from
      epidermis into the receiver compartment was decreased by the presence of HPCD,
      apparently due to the aggregate forming tendency of HPCD. The in vivo delivery of
      CF by electroporation in mice demonstrated the potential of HPCD for sustaining
      the transdermal absorption rate of hydrophilic molecules.

PMID- 15451598
TI  - Alpha-tocopherol pro-vitamins: synthesis, hydrolysis and accumulation in rabbit
      ear skin.
AB  - We synthesized esters of alpha-tocopherol (VE) with the aim to develop new pro
      vitamins, easily reconverted by enzymes in the skin and able to release another
      active moiety such as an amino acid, in order to obtain a synergic effect. In
      particular, the attention was dedicated to the amino acids glycine and alanine
      and to pyroglutamic acid. The sensitivity of pro-vitamins to enzymatic hydrolysis
      was evaluated in vitro using porcine liver esterase. Permeation experiments were
      performed using rabbit ear skin, for the quantification of pro-vitamins and
      derived VE in the epidermis and dermis. The new derivatives synthesized, and in
      particular the glycine and alanine derivatives, accumulated in rabbit skin in a
      significant extent and originated substantial amounts of alpha-tocopherol. In
      comparison with the acetate derivative (VEAc), the amounts accumulated are
      comparable or higher. Moreover, the new derivatives, being more hydrophilic,
      allow the use of vehicles such as the mixture water/propylene glycol/ethanol
      widely employed for the preparation of creams and gels. Finally, the enzymatic
      metabolism of these new derivatives generates not only VE, but also components
      that can have a further advantageous action on skin.

PMID- 15451599
TI  - The influence of plasticizers on the release of theophylline from microporous
      controlled tablets.
AB  - The aim of present work was to investigate the influence of plasticizer on the
      release of theophylline from microporous-controlled tablets. Three plasticizers,
      acetyltributyl citrate (ATBC), castor oil, and triacetin, were included in this
      study. These plasticizers reduced the crystallinity of poly(epsilon-caprolactone)
      (PCL)/poly(ethylene glycol) (PEG)-blended films, and the most prominent change of
      enthalpy of fusion was the film plasticized by triacetin. This might be due to
      triacetin penetrating into both PCL and PEG domains. However, the lipophilic
      property of castor oil only allowed it to alter the crystallization of
      hydrophobic PCL domain. The Young's modulus and the tensile strength of films
      showed a decreased tendency while increasing the amount of plasticizer. The
      change of elongation of plasticized blended films was irregular and was dependent
      of the type of plasticizer. The size of micropores formed in the presence of
      plasticizer was larger than those micropores formed in its absence. The fatty
      plasticizer, castor oil, altered the thermal and mechanical performance and pore
      size of films via soluble in PCL domain, which resulted in the release of
      theophylline from castor oil plasticized-coated tablets, which in turn enhanced
      and closed to a constant release pattern.

PMID- 15451600
TI  - pH-sensitive PEG lipids containing orthoester linkers: new potential tools for
      nonviral gene delivery.
AB  - The synthesis and properties of pH-sensitive polyethylene glycol (PEG) lipids are
      described. The sensitivity of these conjugates to slightly acidic pH was clearly
      related to the structure of the orthoester linkage involved. It was found that pH
      sensitive PEG lipids stabilized cationic lipid/DNA isoelectric complexes as
      efficiently as their non-pH-sensitive PEG analogs at neutral pH. Lowering the pH
      resulted in the precipitation of the complexes bearing pH-sensitive PEG lipids as
      a consequence of their degradation. In contrast, insertion of non-pH-sensitive
      PEG lipids maintained the complex colloidal stability even at lower pH. In vitro
      results showed a significant increase in transfection with formulations
      containing pH-sensitive PEG lipids versus non-pH-sensitive analogs. These
      conjugates show promising properties as lipoplex-stabilizing agents at neutral
      pH, which could be triggered by a mild acidic environment such as that occurring
      in solid tumors, inflammatory tissues, and intracellular endosomal compartments.

PMID- 15451601
TI  - HIV-1 Tat protein transduction domain peptide facilitates gene transfer in
      combination with cationic liposomes.
AB  - The protein transduction domain (PTD) of the HIV-1 Tat protein can facilitate the
      cellular and nuclear uptake of macromolecular particles. Here, we demonstrate
      that incorporation without covalent linkage of a 17-amino acid PTD peptide into
      gene delivery lipoplexes improves gene transfer. Tat/Liposome/DNA (TLD)
      transfection, as evaluated by Fluorescence Activated Cell Scan analysis of a
      Green Fluorescence Protein expression plasmid, enabled transfection of highly
      recalcitrant primary cells in the form of air/liquid interface cultures of sheep
      tracheal epithelium. Treatment with chloroquine increased, and incubation at low
      temperature decreased, TLD transfection, suggesting that the endocytosis uptake
      pathway is involved.

PMID- 15451602
TI  - Enhanced transfection efficiency of PAMAM dendrimer by surface modification with
      L-arginine.
AB  - We designed a novel type of arginine-rich dendrimer, with a structure based on
      the well-defined dendrimer, polyamidoamine dendrimer (PAMAM). Further
      characterization was performed to prove that the polymer is a potent nonviral
      gene delivery carrier. The primary amines located on the surface of PAMAM were
      conjugated with L-arginine to generate an L-arginine-grafted-PAMAM dendrimer
      (PAMAM-Arg). For comparison, an L-lysine-grafted-PAMAM dendrimer (PAMAM-Lys) was
      also generated and compared as a control reagent. The polymers were found to self
      assemble electrostatically with plasmid DNA, forming nanometer-scale complexes.
      From dynamic light scattering experiments, the mean diameter of the polyplexes
      was observed to be around 200 nm. We used PicoGreen reagent as an efficient probe
      for assaying complex formation of polymers with plasmid DNA. The complex composed
      of PAMAM-Arg/DNA showed increased gene delivery potency compared to native PAMAM
      dendrimer and PAMAM-Lys. The cytotoxicity and transfection efficiencies for 293,
      HepG2, and Neuro 2A cells were measured by comparison with PEI and PAMAM. In
      addition, transfection experiments were performed in primary rat vascular smooth
      muscle cells, and PAMAM-Arg showed much enhanced transfection efficiency. These
      findings suggest that the L-arginine-grafted-PAMAM dendrimer possesses the
      potential to be a novel gene delivery carrier for gene therapy.

PMID- 15451603
TI  - Accumulation and depuration of microcystins (cyanobacteria hepatotoxins) in
      Tilapia rendalli (Cichlidae) under laboratory conditions.
AB  - In order to understand accumulation and depuration of microcystins (MCYSTs) in
      Tilapia rendalli, three experiments with juveniles were done. The experiments
      simulated the fish diet during a Microcystis aeruginosa bloom in three different
      situations. In the first one each fish received daily, during 15 days, fish food
      plus toxic cells of M. aeruginosa (20.4 microg MCYSTs fish(-1) day(-1)). In the
      following 15 days they were fed without toxic cells. In the second experiment,
      fish were fed only with toxic cells during 28 days (14.6 microg MCYSTs fish(-1)
      day(-1)) and in the third experiment, during 42 days, fish were fed with fish
      food plus toxic cells (29.2 microg MCYSTs fish(-1) day(-1)) previously disrupted
      (to simulate a senescent bloom). MCYSTs analyses were done by enzyme-linked
      immunosorbent assay (ELISA) in liver and muscle samples in all experiments and in
      faeces in the first one (only in the depuration period). The results demonstrated
      different profiles of MCYSTs accumulation in liver and muscle of T. rendalli.
      Comparing the experiments, the highest MCYSTs accumulation in the liver (2.8
      microg g(-1)) occurred in the second one, where fish had only toxic cells as
      feeding source. In the first experiment, the highest MCYSTs accumulation in liver
      (0.6 microg MCYSTs g(-1)) was observed during the accumulation period, while in
      muscle, interestingly, the highest concentration (0.05 microg MCYSTs g(-1))
      occurred in the depuration period. In this same period, it was also observed
      elimination of toxins through faeces. The second and third experiments showed
      almost the same average concentrations in tissues although fish have received
      more MCYSTs in third one. With respect to implications of the fish comsumption,
      MCYSTs accumulation in muscle of T. rendalli in all three experiments reached
      concentrations that would represent an intake of these toxins above the tolerable
      limit for humans and these results confirmed our previous observations from a
      field study. In conclusion, in this study it was observed that T. rendalli is
      able to accumulate MCYSTs and the availability of other feeding sources, besides
      toxic cells, probably interferes with the accumulation rate. Therefore, the
      occurrence of toxic cyanobacterial blooms produncing MCYSTs in aquaculture ponds
      could represent a risk to the quality of fish to the consumers.

PMID- 15451604
TI  - Successful detection of (anti-)androgenic and aromatase inhibitors in pre
      spawning adult fathead minnows (Pimephales promelas) using easily measured
      endpoints of sexual development.
AB  - Screening assays have been successfully developed for the detection of (anti
      )oestrogenic substances in several fish species, including the fathead minnow
      (Pimephales promelas). Previous work suggested that pre-spawning adult fathead
      minnows might be an appropriate life-stage for developing a screen to detect
      endocrine active substances (EASs). Pre-spawning adult fathead minnows, in which
      their phenotypic sex could be determined, were exposed in flow-through systems to
      three reference substances for 21 days, at 25 degrees C. Male and female fish,
      held in separate tanks, were exposed to dihydrotestosterone (DHT, androgen),
      flutamide (anti-androgen) and fadrozole (aromatase inhibitor). Nominal (mean
      measured) concentrations for DHT were 10 (6.0), 32 (6.1) and 100 (8.6) microg l(
      1), for flutamide, 100 (95.3), 320 (320.4) and 1000 (938.6) microg l(-1) and for
      fadrozole, 25 (24.8), 50 (51.7) and 100 (95.5) microg l(-1). After 14 and 21 days
      exposure, fish were evaluated for growth, secondary sexual characteristics (SSCs,
      number and prominence of nuptial tubercles), gonadosomatic index (GSI) and plasma
      vitellogenin (VTG) concentrations. Development of nuptial tubercles was sensitive
      to both DHT and flutamide exposure. Exposure to DHT significantly increased the
      number of nuptial tubercles (male characteristic) in both males (more abundant)
      and females, after 14 days. Flutamide (938.6 microg l(-1), day 21) significantly
      reduced nuptial tubercle number in male fish. Fadrozole significantly inhibited
      ovarian growth (lower GSI) and significantly induced testis growth (51.7 and 95.5
      microg l(-1)), after 21 days. Plasma VTG concentrations were significantly
      elevated in male fish (6.1 and 8.6 microg l(-1)), but inhibited in female fish
      (6.0 microg l(-1)), exposed to DHT. Flutamide had no effect on plasma VTG in male
      fish, but significantly induced VTG in female fish, after 21 days. Fadrozole
      significantly inhibited VTG in females and induced VTG synthesis in males, at day
      21. These results show that SSCs, GSI and plasma VTG concentrations can be used
      in pre-spawning adult fathead minnows to screen for a range of classes of EASs.
      This work complements other published studies in supporting the current OECD
      effort towards validating a 21 days non-spawning fish screening assay for
      assessing (anti-)oestrogens, aromatase inhibitors and (anti-)androgens.

PMID- 15451605
TI  - Microcosm evaluation of the effects of an eight pharmaceutical mixture to the
      aquatic macrophytes Lemna gibba and Myriophyllum sibiricum.
AB  - Pharmaceuticals have been detected in surface waters of the US and Europe,
      originating largely from two sources, sewage effluent and agricultural runoff.
      These compounds often occur as mixtures leading to potential combined effects. In
      order to investigate the effects of a realistic pharmaceutical mixture on an
      ecosystem, a study utilizing 15 of 12,000 L aquatic microcosms treated with eight
      common pharmaceuticals (atorvastatin, acetaminophen, caffeine, sulfamethoxazole,
      carbamazepine, levofloxacin, sertraline, and trimethoprim) at total (summed)
      molar concentrations of 0, 0.044, 0.608, 2.664, and 24.538 micromol/L (n = 3) was
      conducted. Phytotoxicity was assessed on a variety of somatic and pigment
      endpoints in rooted (Myriophyllum sibiricum) and floating (Lemna gibba)
      macrophytes over a 35-day period. EC10, EC25 and EC50 values were calculated for
      each endpoint exhibiting a concentration-dependent response. Generally, M.
      sibiricum and L. gibba displayed similar sensitivity to the pharmaceutical
      mixture, with phytotoxic injury evident in both species, which was concentration
      dependent. Through single compound 7-day daily static renewal toxicity tests with
      L. gibba, the sulfonamide antibiotic sulfamethoxazole, the fluoroquinolone
      antibiotic levofloxacin and the blood lipid regulator atorvastatin were found to
      be the only compounds to elicit phytotoxic effects in the concentration range
      utilized (0-1000 microg/L). Atorvastatin concentration was highly correlated to
      decreased pigment content in L. gibba, likely inhibiting the known target enzyme
      HMGR, the rate-limiting enzyme in isoprenoid biosynthesis. Hazard quotients were
      calculated for both microcosm and laboratory studies; the highest HQ values were
      0.235 (L. gibba) and 0.051 (L. gibba), which are below the threshold value of 1
      for chronic risks. The microcosm data suggest that at an ecological effect size
      of >20%, biologically significant risks are low for L. gibba and M. sibiricum
      exposed to similar mixtures of pharmaceutical compounds. For M. sibiricum and L.
      gibba, respective minimum differences of 5 and 1%, were detectable, however,
      these effect sizes are not considered ecologically significant.

PMID- 15451606
TI  - Protective effects of allozyme genotype during chemical exposure in the grass
      shrimp, Palaemonetes pugio.
AB  - The primary objective of this research was to determine if the genotype of the
      enzymes glucose phosphate isomerase (Gpi), phosphoglucomutase (Pgm), or mannose
      phosphate isomerase (Mpi) are factors affecting survival during acute endosulfan,
      fluoranthene, and chromium(VI) exposures. Palaemonetes pugio were exposed in the
      laboratory to 6.3 microg/L endosulfan, 100 mg/L chromium(VI), or 0.6 mg/L
      fluoranthene. Dead shrimp were removed at approximately 15-30 min intervals and
      the individual's genotypes for the Gpi, Mpi, and Pgm enzymes were determined.
      These data were used to establish whether allozyme genotype was related to
      tolerance as analyzed with non-parametric methods (i.e. development of survival
      curves using the Kaplan-Meier method of estimation) and parametric methods (i.e.
      proportional hazards models). Since the sex and/or size of the organism was
      expected to affect tolerance, these variables were accounted for in the
      proportional hazards models. Results indicated individuals that were heterozygous
      (MF) for the Gpi allozyme survived longer and had less overall mortality than the
      homozygous MM genotype when exposed to chromium(VI) and to fluoranthene. No
      allozyme genotypes were related to tolerance during the endosulfan exposure when
      sex was included as a covariate in the analysis. These results support the
      hypothesis that there is a genetic basis for tolerance in P. pugio during acute
      exposures to chromium(VI) and to fluoranthene. Although a relationship between
      Gpi genotype and contaminant tolerance has been identified in previous studies,
      no such relationship has been documented in P. pugio or with chromium(VI) as the
      contaminant.

PMID- 15451607
TI  - High sensitivity to chronically elevated CO2 levels in a eurybathic marine
      sipunculid.
AB  - CO2 levels are expected to rise (a) in surface waters of the oceans as
      atmospheric accumulation continues or (b) in the deep sea, once industrial CO2
      dumping is implemented. These scenarios suggest that CO2 will become a general
      stress factor in aquatic environments. The mechanisms of sensitivity to CO2 as
      well as adaptation capacity of marine animals are insufficiently understood.
      Here, we present data obtained in Sipunculus nudus, a sediment-dwelling marine
      worm that is able to undergo drastic metabolic depression to survive regular
      exposure to elevated CO2 levels within its natural habitat. We investigated
      animal survival and the proximate biochemical body composition during long-term
      CO2 exposure. Results indicate an unexpected and pronounced sensitivity
      characterized by the delayed onset of enhanced mortality at CO2 levels within the
      natural range of concentrations. Therefore, the present study contrasts the
      previously assumed high-CO2 tolerance of animals adapted to temporary
      hypercapnia. As a consequence, we expect future loss of species and, thereby,
      detrimental effects on marine benthic ecosystems with as yet poorly defined
      critical thresholds of long-term tolerance to CO2.

PMID- 15451608
TI  - Physiological action of dissolved organic matter in rainbow trout in the presence
      and absence of copper: sodium uptake kinetics and unidirectional flux rates in
      hard and softwater.
AB  - We investigated the physiological effects of dissolved organic matter (DOM) on
      sodium (Na+) transport in juvenile Oncorhynchus mykiss (approximately 2.5 g) in
      the presence and absence of simultaneous acute exposure to copper (Cu2+; 0, 70,
      and 300 microg l(-1)). Trout were acclimated in either hardwater (approximately
      1000 microM Ca2+) or softwater (approximately 100 microM Ca2+), and DOM was
      tested at approximately 8 mg C l(-1) using a natural (NOM) and a commercial (AHA)
      source. Ion transport was evaluated based on kinetics estimates (maximum Na+
      uptake rates, Jmax; substrate affinity, Km) and unidirectional flux measurements
      (Jin, Jout, Jnet). Jmax was higher and unidirectional flux rates were greater in
      softwater-acclimated trout. Fish exposed to DOM alone in hardwater exhibited an
      increased Na+ transport capacity indicated by both the kinetics (67% higher Jmax
      for AHA) and Jin measurements (153% higher for AHA and 125% higher for NOM). In
      softwater, the effects of DOM alone on kinetic parameters and unidirectional flux
      rates were negligible. Cu2+ affected Na+ uptake by a mixed-type inhibition (both
      non-competitive and competitive). In hardwater, only Km was increased (i.e.,
      affinity decreased), whereas in softwater, Km was increased and Jmax was
      decreased, with more marked effects at the higher Cu2+ level. In hardwater, the
      stimulatory effect of AHA on Jmax persisted even in the presence of 300 microg l(
      1) Cu2+, whereas both AHA and NOM prevented the increase in Km caused by Cu2+;
      these effects were reflected in Jin measurements. In softwater, AHA helped to
      protect against the increased Km caused by high Cu2+, but there was no protection
      against the inhibition of Jmax. Unidirectional flux measurements indicated that
      in softwater, Cu2+ inhibited Jin at 70 microg l(-1), whereas at 300 microg l(-1)
      Cu2+, Jout was also stimulated. Fish were more affected by Cu2+ in softwater, as
      indicated by the inability to control diffusive losses of Na+ and a reduced
      ability to take up Na+, but in the presence of DOM, losses were better controlled
      at the end of 6 h exposure. We conclude that DOM has direct effects on the gills,
      as well as protecting fish against acute Cu2+ toxicity. This occurs because DOM
      complexes Cu2+, and because it acts on the transport and permeability properties
      of the gills. These effects differ depending on both water hardness and the
      nature of the DOM source.

PMID- 15451609
TI  - Seasonal variations in antioxidant defences in blue mussels Mytilus edulis
      collected from a polluted area: major contributions in gills of an inducible
      isoform of Cu/Zn-superoxide dismutase and of glutathione S-transferase.
AB  - In the present work, we investigated in the blue mussel (Mytilus edulis) the
      seasonal variations in the activity of several enzymes, which participate in the
      cellular defence system that is involved in the adaptive response of organisms to
      pollution. The activity levels of glutathione S-transferase, glutathione
      peroxidase, glutathione reductase and three isoforms of Cu/Zn-superoxide
      dismutase in gills and digestive glands of this bivalve species were used as
      biomarkers. Adult wild mussels were collected in Le Havre harbour (north-west
      coast of France) from four sites with different environmental conditions.
      Measurements of enzymatic activities were performed on tissue homogenates except
      for Cu/Zn-superoxide dismutase for which the activity of each isoform was
      detected on gel after isoelectric focusing. Seasonal variations in antioxidant
      enzyme activities were observed, characterized by low activity levels during
      winter, a period where oxidative stress is known to be high in bivalves. A clear
      cut discrepancy between tissues was noted concerning inter-individual variability
      of data, which was low in gills but high in digestive gland, leading to the
      conclusion that gills could preferentially be used in biomonitoring studies
      dealing with oxidative stress in the blue mussel. As compared to animals from the
      reference site, mussels from the most polluted sites exhibited changes in the
      Cu/Zn-superoxide dismutase pattern characterized by an increase in the activity
      of the more acidic isoform without significant variation of the total activity of
      the enzyme. The most striking data were recorded in mussels collected at the
      outlet of a thermoelectric power plant. When compared to animals from the
      reference site, not only their gills showed a highly significant induction of the
      most acidic isoform of the Cu/Zn-superoxide dismutase (+340%, P < 0.001) but also
      high levels of glutathione S-transferase activity (+269%, P < 0.001). This study
      points out the usefulness of Cu/Zn-superoxide dismutase expression pattern as a
      biomarker of exposure to environmental stress rather than measurement of total
      activity of the enzyme, in field studies using Mytilus edulis. It also indicates
      the informative potential for glutathione S-transferase measurements in gills and
      underlines the advantages of selecting a battery of biomarkers for evaluating the
      impact of contamination on marine organisms.

PMID- 15451610
TI  - The cattle major histocompatibility complex: is it unique?
AB  - Major histocompatibility complex (MHC) class I genes encode highly polymorphic
      molecules that are expressed on virtually every cell type, and have been
      identified in all but the most primitive vertebrates. They play a number of
      crucial roles in the immune response to infectious disease. Most information
      regarding MHC genes has been generated from humans and mice but, because of the
      great variability found in the MHC system, it is not always possible to
      extrapolate from these to other species. Many strategies have evolved to maximise
      the ability of the MHC to protect individuals and populations against pathogens.
      Cattle MHC class I genes exhibit a number of unusual features. Evidence from
      mapping studies, haplotype and phylogenetic analyses suggests the presence of six
      classical class I loci, in contrast to the more usual two or three, and these are
      expressed in various combinations of one, two or three on different haplotypes.
      Although it remains difficult to assign alleles to loci, it appears that none of
      the loci are expressed on all haplotypes. There is currently limited information
      relating to polymorphism, but various approaches suggest diversity is high, and
      may vary between breeds/populations. Functional consequences of variable MHC
      haplotype composition are discussed. Identifying unique features of the MHC in
      cattle will lead to new insights into evolution of the immune system.

PMID- 15451611
TI  - Lymphocyte subsets and adhesion molecule expression in milk and blood of
      periparturient dairy cattle.
AB  - Fifteen Holstein dairy cattle were monitored for lymphocyte subsets and
      expression of adhesion molecules on cells in milk and blood at parturition and at
      intervals up to 21 days post-partum. Using flow cytometry, we determined
      percentages of T cells (CD4+, CD8+, gammadelta) and B cells from milk and blood
      of these cows. We also measured expression of adhesion molecules (CD62L, LFA-1,
      LPAM-1, and CD44) on lymphocytes in milk and blood. Significantly higher
      percentages of CD8+ cells were found in milk than in blood at all time points
      while significantly higher percentages of B cells were found in blood than in
      milk at all time points. There were minimal to no significant differences in
      percentages of CD4+ or gammadelta+ cells between milk and blood. Expression of
      adhesion molecules was consistently higher on all subsets of milk lymphocytes
      compared with blood lymphocytes. These differences were most pronounced and
      statistically significant at calving and in the first week following calving.
      CD62L, LPAM-1 and CD44 were expressed on a significantly higher percentage of
      lymphocytes in milk at calving than in milk at subsequent sampling times, while
      LFA-1 expression on lymphocytes in milk was significantly lower at calving than
      at subsequent times.

PMID- 15451612
TI  - Allergen-specific immunotherapy induces Th1 shift in dogs with atopic dermatitis.
AB  - Allergen-specific immunotherapy has been applied to canine atopic dermatitis.
      Despite the accumulated clinical evidence of its effect for atopic dogs, the
      basic immunologic mechanisms were not fully understood. In this study, the
      cytokine profile ex vivo in canine atopic dermatitis before and after allergen
      specific immunotherapy was characterized using competitive reverse transcription
      polymerase chain reaction (RT-PCR). Blood samples were collected from 10 dogs
      with atopic dermatitis and peripheral blood mononuclear cells were stimulated
      with house dust mite antigen. The levels of IFN-gamma and IL-4 mRNA were lower in
      atopic dogs compared with non-atopic controls. The ratio of IFN-gamma/IL-4 was
      low in atopic dogs indicating a cytokine profile polarized to Th2. The level of
      IFN-gamma after immunotherapy was significantly higher than that before (P <
      0.05) whereas that of IL-4 mRNA was not changed. Consequently, the ratio of IFN
      gamma/IL-4 after immunotherapy was significantly higher than that before
      immunotherapy (P < 0.05). These results indicate a Th2 cytokine bias is the
      dominant state in atopic dogs and allergen-specific immunotherapy causes a shift
      to wards a Th1 bias by enhancing IFN-gamma expression.

PMID- 15451613
TI  - Identification of guinea pig gammadelta T cells and characterization during
      pulmonary tuberculosis.
AB  - Guinea pigs are an alternative small animal model for many disease studies. Here
      we describe a pan-gammadelta monoclonal antibody (anti-TCRdelta1) specific for
      the constant region of human T cell receptor delta chains that cross-reacts with
      a subpopulation of guinea pig (Cavia porcellus) lymphocytes. The phenotype and
      distribution of this subpopulation is consistent with the guinea pig gammadelta T
      cell subset. FACS analysis of fresh PBMC and splenocytes from naive guinea pigs
      revealed the presence of a subset of cells that stained with the anti-TCRdelta1
      mAb. The relative percentage of anti-TCRdelta1 positive cells in PBMC and tissues
      is similar to that described for gammadelta T cells in other species.
      Immunohistochemistry of tissues also revealed a distribution of anti-TCRdelta1
      positive cells consistent with gammadelta T cells. These data are further
      supported by staining of a polyclonal guinea pig T cell line that became
      progressively CD4 and CD8 negative in long-term culture. Analysis of PBMC from
      guinea pigs following aerosol infection with virulent Mycobacterium tuberculosis
      revealed no apparent changes in the steady-state percentage of blood gammadelta+
      T cells. Taken together, these data suggest that the anti-TCRdelta1 antibody
      recognizes the gammadelta T cell subset in guinea pigs. This reagent may be
      useful for examining gammadelta T cells in various disease models where the
      guinea pig is a more desirable model for study.

PMID- 15451614
TI  - Identification of peptides containing T-cell epitopes of Japanese cedar
      (Cryptomeria japonica) pollen allergen (Cry j 1) in dogs.
AB  - Japanese cedar (Cryptomeria japonica, CJ) pollen has been known to cause atopic
      dermatitis in dogs in Japan. However, since the mechanism of the CJ antigen
      recognition is not well understood in dogs, it is difficult to develop effective
      immunotherapy for atopic dermatitis caused by sensitization to CJ pollen. In
      order to aim at development of a peptide immunotherapy, we tried to identify T
      cell epitopes of a major allergen of CJ pollen, Cry j 1, in dogs sensitive to CJ
      pollen allergen. Peripheral blood mononuclear cells (PBMCs) obtained from 22 dogs
      experimentally sensitized to CJ pollen allergen and 5 atopic dogs sensitive to CJ
      pollen allergen were used for mapping of T-cell epitopes of Cry j 1 using 35
      kinds of synthesized overlapping peptides of Cry j 1. Reactive peptides were
      identified based on the results of blastogenic responses of PBMCs against the
      peptides when the stimulation indices were beyond 2.0. Three reactive peptides
      were identical in a relatively high population of experimental dogs, which were
      Nos. 8 (p71-90) (41%), 10 (p91-110) (50%), and 11 (p101-120) (41%). It was
      considered that these synthesized peptides should contain T-cell epitopes of Cry
      j 1 in the dogs. However, there were no reactive peptides identical among the
      five atopic dogs spontaneously sensitive to CJ pollen. The population of dogs
      experimentally sensitized to CJ pollen antigen will be used in order to
      investigate effects of a peptide immunotherapy using the reactive peptides. The
      results in atopic dogs sensitive to CJ pollen antigen will also provide useful
      information on necessity to develop a tailor-made immunotherapy using reactive
      peptides in each dog.

PMID- 15451615
TI  - Cytopathic and non-cytopathic bovine viral diarrhoea virus biotypes affect fluid
      phase uptake and mannose receptor-mediated endocytosis in bovine monocytes.
AB  - We have used non-cytopathic (ncp) and cytopathic (cp) bovine viral diarrhoea
      viruses (BVDV) to determine how the two biotypes affect mannose receptor (MR)
      mediated endocytosis and fluid phase uptake in bovine monocytes. We have
      demonstrated that endocytosis in uninfected monocytes after 1 h of culture was
      mediated by the MR and fluid phase uptake, and after 24 h of culture it was
      mediated via fluid phase uptake only. Both cp and ncp BVDV affected the
      mechanisms of antigen uptake in monocytes. Endocytosis in BVDV infected
      monocytes, unlike in uninfected cells, was MR-independent and mediated by fluid
      phase uptake after 1 h of infection. The 24-h-BVDV infection changed the antigen
      uptake mechanisms to become MR- and fluid phase uptake-dependent. We conclude
      that antigen uptake, an important antigen presenting cell (APC) function, is
      affected in the early stage of BVDV infection during the first 24 h, with both
      BVDV biotypes, cp and ncp, having similar effects on monocyte antigen uptake in
      cattle. By influencing the early antigen uptake function of APC, BVDV might
      disrupt the function of monocytes as professional APC and contribute to the
      specific immunotolerance to BVDV.

PMID- 15451616
TI  - Variability in cytokine production and cell proliferation by mitogen-activated
      ovine peripheral blood mononuclear cells: modulation by interleukin (IL)-10 and
      IL-12.
AB  - T-cell reactivity is typically measured by cell proliferation and/or production
      of cytokines in response to antigenic/mitogenic stimulation. The choice of assays
      is more limited in ruminants than rodents, and complicated by the variability
      inherent in outbred populations. We have measured proliferation and production of
      interferon-gamma (IFN-gamma) by peripheral blood mononuclear cells (PBMC) from 24
      sheep, and compared the responses between sheep, within sheep over several sample
      points, and also drawn comparisons between the two assays. PBMC derived from
      different sheep varied by as much as ten-fold in both proliferation and IFN-gamma
      production, though not necessarily at the same sample time. Thus, there was a
      poor correlation between the two assays and also considerable variation in the
      responses from the same animal at different time points. Both parameters could be
      modulated by exogenous recombinant ovine interleukin (IL)-10 and IL-12, but we
      were unable to correlate IFN-gamma production with endogenous cytokine production
      in the assays. These data highlight the importance of assay selection for the
      measurement of immune responsiveness and also demonstrate the variation that can
      be expected between sheep and over time.

PMID- 15451617
TI  - Assessment of CD4+ and CD8+ IFN-gamma producing cells by ELISPOT in naive and FIV
      infected cats.
AB  - IFN-gamma is critical for the development of antiviral cell-mediated immunity in
      HIV infected humans and FIV infected cats. The ELISPOT has proven to be a
      technically straightforward assay to quantify the number of IFN-gamma producing
      cells and offers a reasonable alternative for the quantitative measurement of T
      cell function in cats. We used a feline-specific ELISPOT to identify constitutive
      as well as Con A stimulated IFN-gamma production in T-cell subsets and determine
      if there were differences between purified (positively sorted) and negatively
      depleted populations from naive and FIV infected cats. We found no difference in
      the total number of PBMC constitutively producing IFN-gamma in naive and FIV+
      cats. Con A exposure was associated with increased numbers of IFN-gamma producing
      PBMC in naive, but not FIV+, cats. Equivalent numbers of CD4+ and CD8+ T cells
      constitutively expressed IFN-gamma in naive cats. However, in FIV+ cats, the
      number of IFN-gamma producing CD8+ T-cells was approximately two-fold over that
      seen for CD4+ T-cells. We found minimal differences between purified (e.g. CD4+
      or CD8+) and corresponding depleted (e.g. CD8- or CD4-) populations in samples
      from FIV+ cats. In contrast, depleted populations from naive cats showed greater
      response to Con A than did purified populations. Thus, while determination of the
      number of IFN-gamma producing cells by feline-specific ELISPOT is a useful tool
      for the evaluation of the feline immune response, determination of the initial
      sample population and T-cell subset is critical for optimal interpretation of the
      IFN-gamma ELISPOT.

PMID- 15451618
TI  - Characterization of bovine cDNA encoding triggering receptor expressed on myeloid
      cells 1 (TREM-1).
AB  - Triggering receptor expressed on myeloid cells 1 (TREM-1) is a type I
      transmembrane receptor of the immunoglobulin superfamily expressed predominantly
      on neutrophils and monocytes. TREM-1 induces the expression of inflammatory
      cytokines and adhesion molecules, and augments osteoclast, microglia,
      oligodendrocyte, and dendritic cell differentiation. Here, we report the cloning
      of TREM-1 from bovine bone marrow cells. Full-length bovine TREM-1 cDNA is 1202
      base pairs in length and encodes a predicted 232 amino acid peptide. Comparative
      analyses showed that bovine TREM-1 has 48 to 61% amino acid identity with other
      TREM-1 proteins, sharing the greatest identity with porcine TREM-1. Cysteine
      residues characteristic of the immunoglobulin superfamily were conserved in
      bovine TREM-1 and RT-PCR analysis revealed diverse mRNA tissue expression for
      bovine TREM-1. Molecular cloning of bovine TREM-1 extends the repertoire of
      bovine pattern recognition receptors and provides information important for
      investigating their role in bovine innate immunity.

PMID- 15451619
TI  - One-way calcium spill-over during signal transduction in Paramecium cells: from
      the cell cortex into cilia, but not in the reverse direction.
AB  - We asked to what extent Ca(2+) signals in two different domains of Paramecium
      cells remain separated during different stimulations. Wild-type (7S) and pawn
      cells (strain d4-500r, without ciliary voltage-dependent Ca(2+)-channels) were
      stimulated for trichocyst exocytosis within 80 ms by quenched-flow preparation
      and analysed by energy-dispersive X-ray microanalysis (EDX), paralleled by fast
      confocal fluorochrome analysis. We also analysed depolarisation-dependent calcium
      signalling during ciliary beat rerversal, also by EDX, after 80-ms stimulation in
      the quenched-flow mode. EDX and fluorochrome analysis enable to register total
      and free intracellular calcium concentrations, [Ca] and [Ca(2+)], respectively.
      After exocytosis stimulation we find by both methods that the calcium signal
      sweeps into the basis of cilia, not only in 7S but also in pawn cells which then
      also perform ciliary reversal. After depolarisation we see an increase of [Ca]
      along cilia selectively in 7S, but not in pawn cells. Opposite to exocytosis
      stimulation, during depolarisation no calcium spill-over into the nearby cytosol
      and no exocytosis occurs. In sum, we conclude that cilia must contain a very
      potent Ca(2+) buffering system and that ciliary reversal induction, much more
      than exocytosis stimulation, involves strict microdomain regulation of Ca(2+)
      signals.

PMID- 15451620
TI  - Inositol 1,4,5-trisphosphate and ryanodine receptors mobilize calcium from a
      common functional pool in human U373 MG cells.
AB  - This investigation concentrates on the change in Ca(2+) concentration ([Ca(2+)])
      caused by ryanodine in U373 MG cells. This cell type from a human astrocytoma is
      a unique cellular model because it only expresses the type 3 ryanodine receptor
      (RyR3), which is generally the least abundant isoform. In the presence of
      physiological [Ca(2+)] in the extracellular medium, U373 MG cells are caffeine
      insensitive, even after forskolin treatment, and ryanodine-sensitive only when an
      unusually high concentration (30 microM) is applied. Xestospongin C behaves like
      thapsigargin and therefore cannot be used as a selective antagonist of inositol
      1,4,5-trisphosphate receptors (InsP(3)Rs). After ryanodine challenge, addition of
      an analog of Substance P (SP), which should deplete InsP(3)-sensitive stores, has
      no effect on [Ca(2+)](i). After thapsigargin treatment, which unmasks the calcium
      leak from intracellular stores, neither ryanodine nor SP change [Ca(2+)](i),
      suggesting that thapsigargin completely depletes the ryanodine-sensitive and the
      InsP(3)-sensitive stores of U373 MG cells. Finally, in experiments monitoring the
      [Ca(2+)] in intracellular stores, InsP(3) stimulation of permeabilized cells
      causes a decrease in [Ca(2+)] that is not affected by subsequent ryanodine
      treatment. Our results support the conclusion that U373 MG cells express both
      InsP(3)Rs and RyRs that can individually or in combination mobilize only one
      functional Ca(2+) pool.

PMID- 15451621
TI  - Regulation of muscarinic cationic current in myocytes from guinea-pig ileum by
      intracellular Ca2+ release: a central role of inositol 1,4,5-trisphosphate
      receptors.
AB  - The dynamics of carbachol (CCh)-induced [Ca(2+)](i) changes was related to the
      kinetics of muscarinic cationic current (mI(cat)) and the effect of Ca(2+)
      release through ryanodine receptors (RyRs) and inositol 1,4,5-trisphosphate
      receptors (IP(3)Rs) on mI(cat) was evaluated by fast x-y or line-scan confocal
      imaging of [Ca(2+)](i) combined with simultaneous recording of mI(cat) under
      whole-cell voltage clamp. When myocytes freshly isolated from the longitudinal
      layer of the guinea-pig ileum were loaded with the Ca(2+)-sensitive indicator
      fluo-3, x-y confocal imaging revealed CCh (10 microM)-induced Ca(2+) waves, which
      propagated from the cell ends towards the myocyte centre at 45.9 +/- 8.8 microms(
      1) (n = 13). Initiation of the Ca(2+) wave preceded the appearance of any
      measurable mI(cat) by 229 +/- 55 ms (n = 7). Furthermore, CCh-induced [Ca(2+)](i)
      transients peaked 1.22 +/- 0.11s (n = 17) before mI(cat) reached peak amplitude.
      At -50 mV, spontaneous release of Ca(2+) through RyRs, resulting in Ca(2+)
      sparks, had no effect on CCh-induced mI(cat) but activated BK channels leading to
      spontaneous transient outward currents (STOCs). In addition, Ca(2+) release
      through RyRs induced by brief application of 5 mM caffeine was initiated at the
      cell centre but did not augment mI(cat) (n = 14). This was not due to an
      inhibitory effect of caffeine on muscarinic cationic channels (since application
      of 5 mM caffeine did not inhibit mI(cat) when [Ca(2+)](i) was strongly buffered
      with Ca(2+)/BAPTA buffer) nor was it due to an effect of caffeine on other
      mechanisms possibly involved in the regulation of Ca(2+) sensitivity of
      muscarinic cationic channels (since in the presence of 5 mM caffeine,
      photorelease of Ca(2+) upon cell dialysis with 5 mM NP-EGTA/3.8 mM Ca(2+)
      potentiated mI(cat) in the same way as in control). In contrast, IP(3)R-mediated
      Ca(2+) release upon flash photolysis of "caged" IP(3) (30 microM in the pipette
      solution) augmented mI(cat) (n = 15), even though [Ca(2+)](i) did not reach the
      level required for potentiation of mI(cat) during photorelease of Ca(2+) (n =
      10). Intracellular calcium stores were visualised by loading of the myocytes with
      the low-affinity Ca(2+) indicator fluo-3FF AM and consisted of a superficial
      sarcoplasmic reticulum (SR) network and some perinuclear formation, which
      appeared to be continuous with the superficial SR. Immunostaining of the myocytes
      with antibodies to IP(3)R type 1 and to RyRs revealed that IP(3)Rs are
      predominant in the superficial SR while RyRs are confined to the central region
      of the cell. These results suggest that IP(3)R-mediated Ca(2+) release plays a
      central role in the modulation of mI(cat) in the guinea-pig ileum and that IP(3)
      may sensitise the regulatory mechanisms of the muscarinic cationic channels
      gating to Ca(2+).

PMID- 15451622
TI  - Analysis of calcium responses mediated by the A3 adenosine receptor in cultured
      newborn rat cardiac myocytes.
AB  - Intracellular calcium signaling cascade induced by adenosine A(3) receptor
      activation was studied in this work. It was found that adenosine A(3) receptor
      activation (and not A(1) or A(2A) adenosine receptors activation) leads to an
      increase in cytosolic calcium and its further extrusion. A selective A(3) agonist
      Cl-IB-MECA (2-chloro-N(6)-(3-iodobenzyl)adenosine-5'-N-methyluronamide) induced
      an increase in cytoplasmic calcium in a dose-dependent manner, and was
      independent on extracellular calcium. The Ca(2+) signal in newborn
      cardiomyocytes, induced by A(3) receptor activation, is dependent on a pertussis
      toxin-sensitive G-protein. The action of Cl-IB-MECA was not inhibited by an
      inhibitor of phospholipase C (PLC), and by antagonists to inositol 1,4,5
      trisphosphate (IP(3)) receptor. In contrast, inhibition of ryanodine receptor
      prevented calcium elevation induced by this agonist. It was shown that extrusion
      of the elevated cytosolic Ca(2+) was achieved via activation of sarcoplasmic
      reticulum (SR) Ca(2+)-reuptake and of sarcolemmal Na(+)/Ca(2+) exchanger (NCX).
      The increase in the SR Ca(2+)-uptake and NCX Ca(2+) efflux were sufficient not
      only for compensation of Ca(2+) release from SR after A(3) receptor activation,
      but also for an effective prevention of extensive increase in intracellular
      Ca(2+) and may provide mechanism against cellular Ca(2+) overload. In cells with
      elevated [Ca(2+)](i) (due to increase of [Ca(2+)](o)), adenosine or Cl-IB-MECA
      decreased the [Ca(2+)](i) toward diastolic control level, whereas agonist of A(1)
      receptor was ineffective. The protective effect of A(3) receptor agonist was
      abolished in the presence of selective A(3) receptor antagonist MRS1523.

PMID- 15451623
TI  - Ca2+-dependent potentiation of muscarinic receptor-mediated Ca2+ elevation.
AB  - Muscarinic receptor-mediated increases in Ca(2+) in SH-SY5Y neuroblastoma cells
      consist of an initial fast and transient phase followed by a sustained phase.
      Activation of voltage-gated Ca(2+) channels prior to muscarinic stimulation
      resulted in a several-fold potentiation of the fast phase. Unlike the muscarinic
      response under control conditions, this potentiated elevation of intracellular
      Ca(2+) was to a large extent dependent on extracellular Ca(2+). In potentiated
      cells, muscarinic stimulation also activated a rapid Mn(2+) entry. By using known
      organic and inorganic blockers of cation channels, this influx pathway was easily
      separated from the known Ca(2+) influx pathways, the store-operated pathway and
      the voltage-gated Ca(2+) channels. In addition to the Ca(2+) influx, both IP(3)
      production and Ca(2+) release were also enhanced during the potentiated response.
      The results suggest that a small increase in intracellular Ca(2+) amplifies the
      muscarinic Ca(2+) response at several stages, most notably by unravelling an
      apparently novel receptor-activated influx pathway.

PMID- 15451624
TI  - Ca2+ oscillations mediated by exogenous GTP in Paramecium cells: assessment of
      possible Ca2+ sources.
AB  - We applied exogenous guanosine trisphosphate, GTP, to Paramecium tetraurelia
      cells injected with Fura Red for analysing changes of free intracellular Ca(2+)
      concentrations, [Ca(2+)](i), during periodic back-/forward swimming thus induced.
      Strain ginA (non-responsive to GTP) shows no Ca(2+) signal upon GTP application.
      In strain nd6 (normal Ca(2+) signalling) an oscillating [Ca(2+)](i) response with
      a prominent first peak occurs upon GTP stimulation, but none after mock
      stimulation or after 15 min adaptation to GTP. While this is in agreement with
      previous electrophysiological analyses, we now try to identify more clearly the
      source(s) of Ca(2+). Stimulation of nd6 cells, after depletion of Ca(2+) from
      their cortical stores (alveolar sacs), shows the same Ca(2+) oscillation pattern
      but with reduced amplitudes, and a normal behavioural response is observed.
      Stimulation with GTP, supplemented with the Ca(2+) chelator BAPTA, results in
      loss of the first prominent Ca(2+) peak, in reduction of the following Ca(2+)
      amplitudes, and in the absence of any behavioural response. Both these
      observations strongly suggest that for the initiation of GTP-mediated back
      /forward swimming Ca(2+) from the extracellular medium is needed. For the
      maintenance of the Ca(2+) oscillations a considerable fraction must come from
      internal stores, probably other than alveolar sacs, rather likely from the
      endoplasmic reticulum.

PMID- 15451625
TI  - Role of store-dependent influx of Ca2+ and efflux of K+ in apoptosis of CHO
      cells.
AB  - Agents mobilising Ca(2+) from the endoplasmic reticulum are known to activate
      apoptosis. Whatever means are used, the release of Ca(2+) is often followed by a
      store-dependent entry of Ca(2+). Whether apoptosis is triggered by the depletion
      of the stores or by the subsequent store-dependent entry of Ca(2+) is still a
      matter of controversy. Here we studied apoptosis in CHO cells transfected with
      the rat neurotensin (NT) receptor, in which the store-dependent entry of Ca(2+)
      is abolished by repressing the transient receptor potential channel 2 (TRPC2) by
      an antisense oligonucleotide strategy (TRPC2(-) cells) [Cell Calcium 30 (2001)
      157]. When stimulated with thapsigargin (TG), apoptosis occurred in both TRPC2(+)
      and TRPC2(-) cells but 12h earlier in TRPC2(+) cells, suggesting that store
      dependent entry of Ca(2+) can accelerate the process. The expression and
      localisation of caspase-12, an enzyme that has been involved in the apoptosis
      triggered by a stress on the endoplasmic reticulum, was not different in TRPC2(+)
      and TRPC2(-) cells. On the contrary, the expression of GADD153 (Growth Arrest and
      DNA Damage inducible gene 153) triggered by TG treatment depended on external
      Ca(2+) and occurred earlier in TRPC2(+) than in TRPC2(-) cells. In these cells,
      we also noted the presence of K(+) channels activated by Ca(2+) (K(Ca) channels).
      Stimulation of TRPC2(+) cells with TG or with NT triggered a long sustained K(+)
      current, parallel to [Ca(2+)](i) transients, and resulting in a sustained
      hyperpolarisation of the cell membrane. K(+) current and hyperpolarisation were
      transient and not sustained in TRPC2(-) cells. Inhibition of K(Ca) channels with
      charybdotoxin dramatically reduced the K(+) current and also significantly
      brought down the level of apoptosis, suggesting that a prolonged efflux of K(+)
      could be involved in the apoptosis process. We conclude that in CHO cells, store
      dependent entry of Ca(2+) can accelerate apoptosis by accelerating the expression
      of GADD153 and by inducing a prolonged efflux of K(+) out of the cell.

PMID- 15451626
TI  - Vectorial Ca2+ release via ryanodine receptors contributes to Ca2+ extrusion from
      freshly isolated rabbit aortic endothelial cells.
AB  - In this study, we identified ryanodine receptors (RyRs) as a component of a
      cytosolic Ca(2+) removal pathway in freshly isolated rabbit aortic endothelial
      cells. In an earlier article, we reported that the sarco(endo)plasmic reticulum
      Ca(2+)-ATPase (SERCA) and Na(+)/Ca(2+) exchanger (NCX) function in series to
      extrude cytosolic Ca(2+) to the extracellular space. Here we employed caffeine
      and ryanodine as modulators of RyR and showed that they act as the linkage
      between SERCA and NCX in removing Ca(2+) from the cytoplasm. Our data indicate
      that both 15 mM caffeine and 1 microM ryanodine facilitated Ca(2+) extrusion by
      activating RyRs while 100 microM ryanodine had the opposite effect by blocking
      RyRs. A further attempt to investigate RyR pharmacology revealed that in the
      absence of extracellular Ca(2+), ryanodine at 1 microM, but not 100 microM,
      stimulated Ca(2+) loss from the endoplasmic reticulum (ER). Blockade of RyR had
      no effect on the Ca(2+) removal rate when NCX had been previously blocked. In
      addition, the localization of RyR was determined using confocal microscopy of
      BODIPY TR-X fluorescent staining. Taken together, our findings suggest that in
      freshly isolated endothelial cells Ca(2+) is removed in part by transport through
      SERCA, RyR, and eventually NCX, and that RyR and NCX are in close functional
      proximity near the plasma membrane. After blockade of this component, Ca(2+)
      extrusion could be further inhibited by carboxyeosin, indicating a parallel
      contribution by the plasmalemmal Ca(2+)-ATPase (PMCA).

PMID- 15451627
TI  - Protein array method for assessing in vitro biomaterial-induced cytokine
      expression.
AB  - This study demonstrates the feasibility of a cytokine-based in vitro test for
      biomaterials. The combination of monocyte culture and protein array technology
      tested in this study permitted the detection of subtle changes in cytokine
      expression following an exposure to titanium (Ti) particles. However, a broader
      range of materials and sample configurations must be examined before these
      promising results can be translated into a reliable and predictive in vitro
      biomaterials testing protocol. Modified glass slides were robotically printed
      with eight identical arrays consisting of capture antibodies against four mouse
      cytokines [IL-6, TNF-alpha, MIP-2, TGF-beta1] and two positive and two negative
      detection controls. RAW 264.7 mouse monocytes seeded into six-well plates at
      10(5)cells/well were treated with either sterilized Ti particles (test
      biomaterial), or lipopolysaccharide (LPS; positive control), or untreated
      (negative control). Aliquots (80 microl) of culture medium collected at 1, 6, 24,
      48, and 72 h were applied to the protein arrays for simultaneous sandwich
      fluoroimmunoassay, followed by imaging the fluorescent intensities on a
      conventional microarray scanner. LPS induced the release of all four cytokines
      between 1 and 6h treatment periods, whereas Ti induction of cytokines showed a
      gradual and subtle increase in cytokine expression for >24 h. Among the four
      cytokines assayed, TNF-alpha and MIP-2 were most prominently expressed, while IL
      6 was slightly elevated and TGF-beta1 was undetected above background.

PMID- 15451628
TI  - Characterisation of a duplex TiO2/CaP coating on Ti6Al4V for hard tissue
      replacement.
AB  - An initial TiO(2) coating was applied on Ti6Al4V by electrochemical anodisation
      in two dissimilar electrolytes. The secondary calcium phosphate (CaP) coating was
      subsequently applied by immersing the substrates in a simulated body fluid (SBF)
      with three times concentration (SBFx3), mimicking biomineralisation of biological
      bone. Electrochemical impedance spectroscopy and potentiodynamic polarisation
      assessments in SBF revealed that the anodic TiO(2) layer is compact, exhibiting
      up to four-folds improvement in in vitro corrosion resistance over unanodised
      Ti6Al4V. X-ray photoelectron spectroscopy analysis indicates that the anodic Ti
      oxide is thicker than air-formed ones with a mixture of TiO(2-x) compound between
      the TiO(2)/Ti interfaces. The morphology of the dense CaP film formed, when
      observed using scanning electron microscopy, is made up of linked globules 0.1
      0.5microm in diameter without observable delamination. Fourier transform infrared
      spectrometry with an attenuated total internal reflection analysis revealed that
      this film is an amorphous/poorly crystallised calcium-deficient-carbonated CaP
      system. The calculated Ca:P ratios of all samples (1.14-1.28) are lower than
      stoichiometric hydroxyapatite (1.67). These results show that a duplex coating
      consisting of (1) a compact TiO(2) with enhanced in vitro corrosion resistance
      and (2) bone-like apatite coating can be applied on Ti6Al4V by anodisation and
      subsequent immersion in SBF.

PMID- 15451629
TI  - Theoretical analysis of calcium phosphate precipitation in simulated body fluid.
AB  - The driving force and nucleation rate of calcium phosphate (Ca-P) precipitation
      in simulated body fluid (SBF) were analyzed based on the classical
      crystallization theory. SBF supersaturation with respect to hydroxyapatite (HA),
      octacalcium phosphate (OCP) and dicalcium phosphate (DCPD) was carefully
      calculated, considering all the association/dissociation reactions of related ion
      groups in SBF. The nucleation rates of Ca-P were calculated based on a kinetics
      model of heterogeneous nucleation. The analysis indicates that the nucleation
      rate of OCP is substantially higher than that of HA, while HA is most
      thermodynamically stable in SBF. The difference in nucleation rates between HA
      and OCP reduces with increasing pH in SBF. The HA nucleation rate is comparable
      with that of OCP when the pH value approaches 10. DCPD precipitation is
      thermodynamically impossible in normal SBF, unless calcium and phosphate ion
      concentrations of SBF increase. In such case, DCPD precipitation is the most
      likely because of its highest nucleation rates among Ca-P phases. We examined the
      influences of different SBF recipes, interfacial energies, contact angle and
      molecular volumes, and found that the parameter variations do not have
      significant impacts on analysis results. The effects of carbonate incorporation
      and calcium deficiency in HA were also estimated with available data. Generally,
      such apatite precipitations are more kinetically favorable than HA.

PMID- 15451630
TI  - Native fibrillar collagen membranes of micron-scale and submicron thicknesses for
      cell support and perfusion.
AB  - Fibrillar type I collagen is nontoxic, biocompatible, and possesses considerable
      strength and stability. In a study of scaffolds for use in laminated tissue
      substitutes, we examined the properties of membranes made from air-dried
      hydrogels of collagen fibrils that were polymerized from native, monomeric
      collagen. Planar collagen membranes (CMs) of 0.1-5.3 microm dry thickness were
      made by variation of the collagen concentration and/or the volume of the
      hydrogel. The planar CMs, which were comprised of a dense feltwork of long
      collagen fibrils 70-100 nm in diameter, showed considerable resistance to rupture
      and retained their membranous character after 6 weeks in tissue culture medium at
      37 degrees C. CMs that were relatively thick when dry exhibited a greater
      proportional increase in rehydrated thickness and a greater diffusivity (when
      rehydrated) to 4.3 kDa dextran than did CMs that were relatively thin when dry.
      Hollow, tubular CMs of several configurations were prepared by embedment of
      solid, removable forms into collagen hydrogels prior to drying. By use of special
      fixtures, a planar CM that incorporated multiple, parallel tubes was fabricated.
      In summary, hydrogels of fibrillar collagen can be transformed into membranous
      structures suitable for tissue engineering applications.

PMID- 15451631
TI  - Synergistic interaction of topographic features in the production of bone-like
      nodules on Ti surfaces by rat osteoblasts.
AB  - The objective of this study was to study the responses of osteoblast-like cells
      to rough Titanium (Ti)-coated epoxy surfaces of differing topographic complexity.
      Four topographies were studied: polished (PO), coarse-blasted (CB), acid-etched
      (AE) and coarse-blasted+acid-etched (SLA). Rat osteoblasts were cultured on these
      surfaces and their morphology, thickness as well as the number and size of bone
      like nodules measured. To determine cell shape and cell thickness, fluorescein-5
      thiosemicarbazide was used to stain the cell components including the cell
      membrane, the stained cells were optically sectioned using epifluorescent
      microscopy and the optical sections were computationally reconstructed to obtain
      three-dimensional images in which cell volume and cell thickness could be
      determined. Similarly optical sections of bone-like nodules labeled with
      tetracycline were also reconstructed to determine their size. The different
      surface topographies were found to alter the thickness and morphology of
      osteoblasts cultured on these surfaces. Osteoblasts produced significantly more
      and larger nodules on SLA compared to other surfaces. Nevertheless and perhaps
      surprisingly, given the evidence in various cell populations that cell shape can
      affect cell differentiation, cell thickness was not directly correlated with an
      increase in bone-like nodule formation. Data were analyzed by factorial analysis
      of variance. In this way the primary effect of each surface treatment ( i.e.
      blasting and acid etching) could be assessed as well as their interaction. Both
      the acid etching and blasting processes significantly affected the number and
      size of bone-like nodules cultured on Ti surfaces. Moreover there were
      significant interaction effects indicating that surface topographic features can
      act synergistically to enhance bone formation. This result suggests that a useful
      approach to the optimization of surfaces for bone production could involve
      systematic investigation of combinations of processes each of which produces
      distinct surface topographical features.

PMID- 15451632
TI  - Bone inductive properties of rhBMP-2 loaded porous calcium phosphate cement
      implants inserted at an ectopic site in rabbits.
AB  - Recombinant human bone morphogenetic protein-2 (rhBMP-2) is known for its
      osteoinductive potential in bone tissue engineering. Calcium phosphate (Ca-P)
      cements are injectable, osteoconductive ceramic materials in which a macroporous
      structure can be induced during the setting reaction. In this study, the
      osteoinductive capability of rhBMP-2 loaded porous Ca-P cement was evaluated.
      Porous Ca-P cement discs were made and loaded with rhBMP-2 in vitro and implanted
      subcutaneously in the back of New Zealand white rabbits. The implantation period
      was either 2 or 10 weeks. Histological analysis of retrieved specimens revealed
      evident bone formation in the rhBMP-2 loaded Ca-P cement discs (pore fill: 18+/
      6%) after 10 weeks of implantation. Bone formation occurred only in rhBMP-2
      loaded porous Ca-P cement discs. Degradation of the Ca-P cement could not be
      confirmed after 10 weeks of implantation. The scaffold maintained its shape and
      stability during this time period. We conclude that porous Ca-P cement is a
      suitable carrier material for ectopic bone engineering.

PMID- 15451633
TI  - Enhanced neovasculature formation in ischemic myocardium following delivery of
      pleiotrophin plasmid in a biopolymer.
AB  - Coronary heart disease is currently the leading killer in the western world.
      Therapeutic angiogenic agents are currently being examined for treatment of this
      disease. We have recently demonstrated the effective use of Pleiotrophin (PTN) as
      a therapeutic agent for treatment of ischemic myocardium. We have also shown that
      injection of the biopolymer fibrin glue preserves left ventricular geometry and
      prevents a deterioration of cardiac function following myocardial infarction. Due
      to the low transfection efficiency of naked plasmid injections, we examined the
      use of PTN plasmid and the biopolymer as a gene-activated matrix in the
      myocardium. In this study, we demonstrate that delivery of PTN plasmid in fibrin
      glue increases neovasculature formation compared to injection of the naked
      plasmid in saline.

PMID- 15451634
TI  - Micro-rotary fatigue of tooth-biomaterial interfaces.
AB  - The bonding effectiveness of restorative materials to tooth tissue is typically
      measured statically. Clinically tooth/composite bonds are however subjected to
      cyclic sub-critical loads. Therefore, in vitro fatigue testing of dental
      adhesives should predict better the in vivo performance of adhesives. The
      objective of this study was to determine the fatigue resistance of two
      representative adhesives, a self-etch and an etch&rinse adhesive, bonded to
      enamel and dentin. Therefore, tooth/composite interfaces were cyclically loaded
      using a miniaturized version of a rotating beam fatigue testing device.
      Subsequently, the load at which 50% of the specimens fail after 10(5) cycles, was
      determined as the median micro-rotary fatigue resistance (microRFR). For both
      adhesives, the microRFR was about 30-40% lower than the corresponding micro
      tensile bond strength (microTBS) to both enamel and dentin. Analysis of the
      fracture surfaces by Feg-SEM revealed typical fatigue fracture patterns. It is
      concluded that resin/tooth interfaces are vulnerable to progressive damage by sub
      critical loads, with the 3-step etch&rinse adhesive being more resistant to
      fatigue than the 2-step self-etch adhesive.

PMID- 15451635
TI  - Enhancement of implantable glucose sensor function in vivo using gene transfer
      induced neovascularization.
AB  - The in vivo failure of implantable glucose sensors is thought to be largely the
      result of inflammation and fibrosis-induced vessel regression at sites of sensor
      implantation. To determine whether increased vessel density at sites of sensor
      implantation would enhance sensor function, cells genetically engineered to over
      express the angiogenic factor (AF) vascular endothelial cell growth factor (VEGF)
      were incorporated into an ex ova chicken embryo chorioallantoic membrane (CAM)
      glucose sensor model. The VEGF-producing cells were delivered to sites of glucose
      sensor implantation on the CAM using a tissue-interactive fibrin bio-hydrogel as
      a cell support and activation matrix. This VEGF-cell-fibrin system induced
      significant neovascularization surrounding the implanted sensor, and
      significantly enhanced the glucose sensor function in vivo. This model system,
      for the first time, provides the "proof of principle" that increasing vessel
      density at the sites of implantation can enhance glucose sensor function in vivo,
      and demonstrates the potential of gene transfer and tissue interactive fibrin bio
      hydrogels in the development of successful implants.

PMID- 15451636
TI  - Protein-mediated boundary lubrication in arthroplasty.
AB  - Wear of articulated surfaces can be a major lifetime-limiting factor in
      arthroplasty. In the natural joint, lubrication is effected by the body's natural
      synovial fluid. Following arthroplasty, and the subsequent reformation of the
      synovial membrane, a fluid of similar composition surrounds the artificial joint.
      Synovial fluid contains, among many other constituents, a substantial
      concentration of the readily adsorbing protein albumin. The ability of human
      serum albumin to act as a boundary lubricant in joint prostheses has been
      investigated using a pin-on-disc tribometer. Circular dichroism spectroscopy was
      employed to follow the temperature- and time-dependent conformational changes of
      human serum albumin in the model lubricant solution. Effects of protein
      conformation and polymer surface hydrophilicity on protein adsorption and the
      resulting friction in the boundary lubrication regime have been investigated.
      Unfolded proteins preferentially adsorb onto hydrophobic polymer surfaces, where
      they form a compact, passivating layer and increase sliding friction-an effect
      that can be largely suppressed by rendering the substrate more hydrophilic. A
      molecular model for protein-mediated boundary friction is proposed to consolidate
      the observations. The relevance of the results for in vivo performance and ex
      vivo hip-joint testing are discussed.

PMID- 15451637
TI  - Dendrimers of citric acid and poly (ethylene glycol) as the new drug-delivery
      agents.
AB  - Citric acid-polyethylene glycol-citric acid (CPEGC) triblock dendrimers as
      biocompatible compounds containing G(1), G(2) and G(3) were applied as the drug
      delivery systems. Some of the small size molecules and drugs are trapped with the
      above-synthesized dendrimers. The guest molecules, which are hydrophobic when
      trapped into the suitable sites of dendrimers, are becoming soluble in aqueous
      solution. The quantity of trapped molecules and drugs such as 5-amino salicylic
      acid (5-ASA), pyridine, mefenamic acid, and diclofenac was measured. The
      drug/dendrimer complexes remained in room temperature for about 10 months and
      after this long time they were stable and the drugs were not released. Also, the
      controlled release of the above-mentioned molecules and drugs in vitro conditions
      was investigated. The structure definition and controlled release of the
      molecules and drugs were carried out using different spectroscopy methods.

PMID- 15451638
TI  - In vitro drug release studies from the polymeric hydrogels based on HEA and HPMA
      using 4-[(E)-[(3Z)-3-(4-(acryloyloxy)benzylidene)-2-hexylidene]methyl]phenyl
      acrylate as a crosslinker.
AB  - Novel crosslinker, 4-[(E)-[(3Z)-3-(4-(acryloyloxy)benzylidene)-2
      hexylidene]methyl]phenyl acrylate (AMA) was synthesized using (2Z, 6E)-2,6-bis(4
      hydroxybenzylidene)cyclohexanone (HBC) and acryloyl chloride. Two types of
      crosslinked polymeric hydrogels were prepared from 2-hydroxyethyl acrylate (HEA)
      and 2-hydroxypropyl methacrylate (HPMA) monomers using AMA as a crosslinking
      agent. 2',4-dichloro-5'-fluoro-1-ene-2-(4-hydroxyphenyl)phenone (EHP) (J. Bio
      Active Compat. Polym. 18 (2003) 219) was used as a drug molecule for monitoring
      the releasing behaviour of the hydrogels. Morphology of the hydrogels was
      characterized using optical microscopy (OM) and Scanning Electron Microscopy
      (SEM) techniques. Several modifications were made in the experimental sections to
      study the effect of crosslinking percentage (CLP), drug loading percentage (DLP),
      monomer type (HEA and HPMA) and the pH. Totally 18 experiments were carried out
      to study the desired parameters in the hydrogels. The drug-releasing rate was
      monitored by the absorption appeared at 330.5 nm using UV spectrometer. It was
      found that the releasing rate of the drug from the polymeric hydrogels was
      dependent on the crosslinking density, drug loading percentage, monomer type and
      pH of the medium.

PMID- 15451639
TI  - Mechanistic aspects of in vitro fatigue-crack growth in dentin.
AB  - Although the propagation of fatigue cracks has been recognized as a problem of
      clinical significance in dentin, there have been few fracture mechanics-based
      studies that have investigated this issue. In the present study, in vitro cyclic
      fatigue experiments were conducted over a range of cyclic frequencies (1-50 Hz)
      on elephant dentin in order to quantify fatigue-crack growth behavior from the
      perspective of understanding the mechanism of fatigue in dentin. Specifically,
      results obtained for crack extension rates along a direction parallel to the
      dentinal tubules were found to be well described by the stress-intensity range,
      DeltaK, using a simple Paris power-law approach with exponents ranging from 12 to
      32. Furthermore, a frequency dependence was observed for the crack-growth rates,
      with higher growth rates associated with lower frequencies. By using crack-growth
      experiments involving alternate cyclic and static loading, such fatigue-crack
      propagation was mechanistically determined to be the result of a "true" cyclic
      fatigue mechanism, and not simply a succession of static fracture events.
      Furthermore, based on the observed frequency dependence of fatigue-crack growth
      in dentin and observations of time-dependent crack blunting, a cyclic fatigue
      mechanism involving crack-tip blunting and re-sharpening is proposed. These
      results are deemed to be of importance for an improved understanding of fatigue
      related failures in teeth.

PMID- 15451640
TI  - Effects of environmental enrichment on males of a docile inbred strain of mice.
AB  - Environmental enrichment is intended to improve the welfare of laboratory
      animals. However, regarding male mice, numerous studies indicate an increase in
      aggressive behavior due to cage structuring. On the one hand, this might be a
      problem concerning animal welfare. On the other hand, enrichment is though to
      hamper environmental standardization and to increase variability of data.
      Furthermore, increasing fights, arousal, and/or injury in enriched housed animals
      might superimpose other (positive) environmental effects on behavior and
      physiology. Therefore, the present study investigated effects of environmental
      enrichment on behavioral, endocrinological, and immunological parameters in male
      mice of the docile inbred strain ABG. From weaning until day 77+/-3 of life,
      animals were kept in stable sibling groups of four under three different housing
      conditions: (A) nonstructured Makrolon type III laboratory cages ("standard
      housing"=S); (B) equivalent laboratory cages that were enriched with a box and
      scaffolding ("enriched housing"=E); and (C) spacious terrariums that were
      structured richly ("super-enriched housing"=SE). No differences in agonistic
      behavior, levels of plasma corticosterone (CORT), and activities of adrenal
      tyrosine hydroxylase (TH) existed among S-, E-, and SE-housed ABG males. Play
      behavior and general activity increased significantly with increasing enrichment.
      Concerning immunological parameters, males of both forms of enriched housing
      showed significantly lower percentages of CD4 and CD8 cells compared to S-housed
      mice. However, regarding the ratio of CD4/CD8 cells, IL-2, IL-4, IL-10, IFN
      gamma, IgG1, and IgG2a, no significant housing-dependent differences were found.
      Enrichment did neither hamper standardization nor negatively influence the
      variability of physiological parameters. In summary, using a docile strain of
      mice revealed the positive effects of environmental enrichment also on male mice.
      The lack of adverse effects on behavior, physiology, standardization, and
      variability of data defuses these arguments against providing docile male mice
      with enrichment.

PMID- 15451641
TI  - Devazepide fails to reverse the inhibitory effect of interleukin-1beta on food
      intake in female rats.
AB  - Proinflammatory cytokines released during the course of infection elicit numerous
      behavioral and metabolic changes. The decrease in food intake that accompanies
      infection is mediated in part by interleukin-1 (IL-1). Cholecystokinin (CCK) is a
      neuropeptide released during a meal, decreases food intake, and previous research
      suggests that CCK mediates the anorectic action of IL-1. The effects of estrogen
      on food intake are also thought to involve CCK, as the satiety action of CCK is
      increased by estradiol in both intact and ovariectomized rats. Estradiol also
      modulates many of the behavioral and physiological effects of IL-1. The present
      experiment examined the ability of the CCK(A) receptor antagonist devazepide to
      block the effects of IL-1 and estradiol on food intake in female rats. Adult
      animals were ovariectomized and given two daily subcutaneous injections of
      estradiol benzoate (EB; 5.0 microg) or the oil vehicle 3 weeks after surgery.
      Three days after treatment onset, animals were pretreated with devazepide or its
      vehicle 30 min prior to intraperitoneal injections of IL-1beta (4.0 microg/kg) or
      saline given 1 h before light offset. Food and water intake was measured
      following 2 h of spontaneous feeding. The results indicate that devazepide failed
      to reverse the anorectic action of IL-1beta, although the effects of estradiol on
      food intake were blocked by devazepide. These data do not support a role for CCK
      in IL-1-induced anorexia, and suggest that cytokines may act directly on neural
      systems involved in the control of food intake.

PMID- 15451642
TI  - Interaction of microwaves and a temporally incoherent magnetic field on spatial
      learning in the rat.
AB  - The effect of a temporally incoherent magnetic field ('noise') on microwave
      induced spatial learning deficit in the rat was investigated. Rats were trained
      in six sessions to locate a submerged platform in a circular water maze. Four
      treatment groups of rats were studied: microwave-exposure (2450-MHz continuous
      wave microwaves, power density 2 mW/cm(2), average whole-body specific absorption
      rate 1.2 W/kg), 'noise' exposure (60 mG), 'microwave+noise' exposure, and sham
      exposure. Animals were exposed to these conditions for 1 h immediately before
      each training session. One hour after the last training session, animals were
      tested in a 2-min probe trial in the maze during which the platform was removed.
      The time spent during the 2 min in the quadrant of the maze in which the platform
      had been located was scored. Results show that microwave-exposed rats had
      significant deficit in learning to locate the submerged platform when compared
      with the performance of the sham-exposed animals. Exposure to 'noise' alone did
      not significantly affect the performance of the animals (i.e., it was similar to
      that of the sham-exposed rats). However, simultaneous exposure to 'noise'
      significantly attenuated the microwave-induced spatial learning deficit (i.e.
      'microwave+noise'-exposed rats learned significantly better than the microwave
      exposed rats). During the probe trial, microwave-exposed animals spent
      significantly less time in the quadrant where the platform was located. However,
      response of the 'microwave+noise'-exposed animals was similar to that of the sham
      exposed animals during the probe trial. Thus, simultaneous exposure to a
      temporally incoherent magnetic field blocks microwave-induced spatial learning
      and memory deficits in the rat.

PMID- 15451643
TI  - Effects of midbrain lesions on lordosis and ultrasound production.
AB  - Previous studies suggest the control of lordosis by competing neural systems. A
      lordosis-inhibiting system is thought to originate in the lateral septum (LS) or
      preoptic area (POA) and project to midbrain sites, including the ventral
      tegmental area (VTA) and ventral half of the periaqueductal gray (vPAG). A
      lordosis-facilitating system is thought to originate in the ventromedial
      hypothalamus and project to the dorsal half of the PAG (dPAG). To test the
      generality of this model, we subjected female hamsters to control operations or
      lesions of the dPAG, vPAG or VTA. Subjects in hormone-induced estrus were
      observed for lordosis responses to males and manual stimulation and for rates of
      production of the "ultrasounds" used by hamsters for courtship. PAG lesions of
      both types depressed ultrasound rate, lordosis initiation and lordosis
      maintenance. VTA lesions failed to affect ultrasound rate, lordosis maintenance
      or lordosis responses to males. However, damage to the dorsomedial tegmentum was
      correlated with deficits in lordosis initiation. These results suggest the
      concentration in the PAG of mechanisms controlling vocalizations, including the
      ultrasounds used by hamsters for courtship. They confirm midbrain control of
      lordosis initiation and maintenance but fail to support any simple specialization
      of dorsal and ventral areas for these dimensions. They also fail to support a
      specialization of the dorsal and ventral halves of the midbrain for lordosis
      facilitation and inhibition, but do suggest several midbrain areas likely to be
      involved in the first of these functions.

PMID- 15451644
TI  - Is there a parotid-salivary reflex response to fat stimulation in humans?
AB  - The perception of fats in foods may involve gustatory, olfactory or textural
      cues. There is contradictory evidence as to whether the orosensory perception of
      fat is as a basic quality of taste or related to the physical characteristics of
      fat. A dose-response reflex parotid-salivary secretion has, however, been shown
      for the accepted basic taste qualities. The aim of this study was to establish
      whether varying fat concentration in two food types causes an associated dose
      response reflex parotid secretion in humans. Parotid salivary flow was recorded
      using Lashley cups and cannulae connected to an instantaneous flow meter.
      Gustatory stimuli were achieved using 3 ml of skimmed (0.1% fat), semi-skimmed
      (1.7% fat) or full (3.6% fat) milk (Sainsbury) or 5 g of extra-light (5% fat),
      light (16% fat) or original (24% fat) cream cheese (Kraft). No significant
      differences in salivary flow rate were shown within the milk group (n=10, P=.93)
      or within the cream-cheese group (n=11, P=.82). Furthermore, no correlation was
      observed between increasing fat concentration and flow within either the milk
      (P=.98) or the cream-cheese group (P=.69; Pearson Product Moment Correlation).
      These results do not support the hypothesis that there is a fat-specific dose
      response parotid reflex.

PMID- 15451645
TI  - Pregnancy-related changes in behavior and cardiac activity in primiparous pigs.
AB  - Pregnancy in mammals is a time of considerable physical, physiological and
      behavioral change necessary for the continuance of the gestation. Gestating pigs
      are often used in behavior and welfare studies; yet, there are little published
      data describing how pregnancy affects normal behavior and cardiac activity
      patterns. The objective of this work was to describe the longitudinal dynamics of
      cardiac activity and behavior during pregnancy in primiparous pigs (gilts). The
      behavior and cardiac activity of nine gilts were recorded on eight occasions at
      certain fixed time points during their pregnancy: 1-2 weeks before oestrus and
      mating (week -1), 14 days postmating (week 2), and days 30 (week 4), 44 (week 6),
      65 (week 9), 79 (week 11), 93 (week 13) and 107 (week 15) of pregnancy. Temporal
      changes in behavior patterns were present in all gilts over the course of
      gestation. Pretest levels of general activity progressively declined between
      weeks -1 and 15, as indicated by a decrease in the proportion of observations
      spent rooting (p<0.001), walking (p<0.001) and standing (p<0.001). There was a
      corresponding increase in inactivity (p<0.001), and the proportion of time spent
      sleeping, as opposed to lying alert, increased also (p<0.001). Apart from RR-min
      and its corresponding HR-max indices, all time-domain parameters were influenced
      by the stage of gestation. Specifically, mean HR increased (p<0.001), whereas the
      root-mean-square of successive differences (RMSSD) and standard deviation (S.D.)
      decreased (p<0.001). Pregnancy further impacted the frequency domain measures of
      heart rate variability. From week -1 to 15, the absolute magnitude of Total power
      (p<0.001) decreased, HF power decreased (p<0.001) and LF power increased
      (p=0.004). In conclusion, pregnancy induced widespread changes in behavior and in
      sympathovagal regulation of cardiac activity in pigs that were reflected in both
      the time and frequency domain indices of heart rate variability analysis.

PMID- 15451646
TI  - Analysis of the cold-water restraint procedure in gastric ulceration and body
      temperature.
AB  - Gastric mucosal injury induced by body restraint can be enhanced when combined
      with cold-water immersion. Based on this fact, the present study had two main
      purposes: (i) to examine the contribution of each of these two forms of stress on
      the development of gastric ulceration and regulation of body temperature and (ii)
      to investigate the importance of the animal's consciousness on gastric ulceration
      induced by the cold-water restraint. Independent groups of animals were exposed
      for 3 h to one of the following stressful treatments: body restraint plus cold
      water (20+1 degrees C) immersion, body restraint alone or cold-water immersion
      alone. Control animals were not exposed to any form of stress. Half of the
      animals submitted to each of the four treatments were anesthetized with
      thionembutal (35 mg/kg), whereas the other half was injected with saline. Results
      indicated that body restraint alone was not sufficient to induce gastric
      ulceration or changes in body temperature. On the other hand, cold-water
      exposure, either alone or in conjunction with body restraint, induced the same
      amount of stomach erosions and hypothermia. Therefore, it appears that body
      restraint does not play an important role on gastric ulceration induced by the
      cold-water restraint procedure. Present results also indicated that conscious and
      anesthetized animals immersed in cold water presented robust gastric ulceration
      and a marked drop in body temperature. However, conscious animals developed more
      severe gastric damage in comparison to anesthetized animals although both groups
      presented the same degree of hypothermia. These findings suggest that hypothermia
      resulting from cold-water exposure has a deleterious effect on gastric ulceration
      but the animal's conscious activity during the cold-water immersion increases the
      severity of gastric mucosal damage. It is concluded that cold-water restraint is
      a useful procedure for the study of the underlying mechanisms involved in stress
      induced ulceration.

PMID- 15451647
TI  - Reduced violent behavior following biochemical therapy.
AB  - Reduced violent behavior following biochemical therapy. We conducted an outcome
      study to measure the effectiveness of biochemical therapy for 207 consecutive
      patients presenting with a diagnosed behavior disorder. The treatment protocols
      were based on clinical evaluation and our past experience in the treatment of
      8000 patients with behavior disorders at the Pfeiffer Treatment Center (PTC) over
      a 10-year period. Each test subject was screened for chemical imbalances
      previously found in high incidence in this population, including metal-metabolism
      disorders, methylation abnormalities, disordered pyrrole chemistry, heavy-metal
      overload, glucose dyscontrol, and malabsorption. The clinical procedure included
      a medical history, assay of 90 biochemical factors, and a physical examination.
      Standardized treatment protocols were applied for each imbalance that was
      identified. The frequencies of physical assaults and destructive episodes were
      determined using a standardized behavior scale before and after treatment, with
      follow-up ranging from 4 to 8 months. RESULTS: Seventy-six percent of the test
      subjects achieved compliance during the treatment period. The remaining 24% were
      reported to have discontinued the therapy. A reduced frequency of assaults was
      reported by 92% of the compliant assaultive patients, with 58% achieving
      elimination of the behavior. A total of 88% of compliant destructive patients
      exhibited a reduced frequency of destructive incidents and 53% achieved
      elimination of the behavior. Statistical significance was found for reduced
      frequency of assaults (t=7.74, p<0.001) and destructive incidents (t= 8.77,
      p<0.001). The results of this outcome study strongly suggest that individualized
      biochemical therapy may be efficacious in achieving behavioral improvements in
      this patient population.

PMID- 15451648
TI  - Can energy drinks reduce the depressor effect of ethanol? An experimental study
      in mice.
AB  - Although the popularization of the combined use of alcoholic beverages and energy
      drinks (ED) containing caffeine, taurine and other substances has increased,
      there are no controlled experimental studies on the effects of ED alone or
      combined with ethanol. This work aimed at evaluating the effects of different
      doses of ED combined or not with ethanol, on the locomotor activity of Swiss
      mice. The administration of 3.57, 10.71 or 17.86 ml/kg of ED alone increased the
      locomotor activity of the animals in relation to a control group. Low doses of
      ethanol (0.5, 1.0 and 1.5 g/kg) alone or in combination with 10.71 ml/kg of ED
      did not affect their locomotor activity. However, the reduction of activity
      observed after 2.5 g/kg of ethanol was antagonized by 10.71 ml/kg of ED. Further
      studies on the mechanisms of this interaction are still needed.

PMID- 15451649
TI  - Chronic fatigue syndrome impairs circadian rhythm of activity level.
AB  - Some of the symptoms of chronic fatigue syndrome (CFS) are the same as for
      disrupted circadian rhythm. Activity level is frequently used to study circadian
      rhythm. Continuous waist activity measurements taken every minute 24 h/day for
      from 5 to 7 days in 10 controls and from 2 to 7 days in 8 patients with CFS
      yielded two primary findings: (a) lower daytime activity and (b) less regular
      activity-rest cycles in persons with CFS than in controls.

PMID- 15451650
TI  - Serotonin involvement in the electroacupuncture- and moxibustion-induced gastric
      emptying in rats.
AB  - OBJECTIVE: Electroacupuncture (EA) as well as moxibustion stimulation has been
      reported to produce an excitatory effect on the gastrointestinal motility of the
      rat. Serotonergic neurons of the mioenteric and submucous plexus are major
      participants in the gastrointestinal physiology. Here, we compared the outcomes
      of the stimulation of a specific set of acupoints with either acupuncture or
      moxibustion on the gastrointestinal motility and the role of serotonin (5-HT) in
      this effect. METHODS: To analyze the role of 5-HT on the gastrointestinal
      motility of the rat, we studied the flow of 25 glass beads administered to the
      stomach, after treatment of the animals with a serotonin inhibitor (para
      chlorophenylalanine [pCPA]). Acupuncture stimulation was performed on acupoints
      St-36 (Zusanli) and Sp-6 (Sanyinjiao), with electrical stimulation, or on
      acupoints Ren-10 (Xiawan), Ren-12 (Zhongwan) and St-25 (Tianshu), with
      moxibustion. Animals subjected to sham stimulation were used as controls in
      addition to naive, unstimulated animals. RESULTS: Stimulation of the hind limb
      (St-36 and Sp-6) and abdominal (Ren-10, Ren-12, St-25) acupoints resulted in
      effective gastric emptying, as compared with sham-stimulated animals.
      Pretreatment of animals with pCPA abolished either the response provided by
      acupuncture stimulation in animal groups subjected to hind limb acupoints or the
      response provided by moxibustion stimulation in abdominal acupoints. CONCLUSION:
      Our data suggest that moxibustion in the abdominal points and EA in the hind limb
      require an intact serotonergic pathway. In addition, we suggest that this
      involvement of serotonin is a general feature of the mediated effects of
      acupuncture on gastric emptying of the rat.

PMID- 15451651
TI  - Cannabinoid (CB)1 receptor antagonist, AM 251, causes a sustained reduction of
      daily food intake in the rat.
AB  - Cannabinoid (CB)(1) receptors are present throughout the nervous system,
      including several areas implicated in the control of food intake. Central and
      peripheral administration of CB(1) agonists increase food intake while CB(1)
      receptor antagonists reduce food intake. However, in some previous studies,
      tolerance to the anorectic effects of CB(1) antagonists develops within days. To
      further delineate the role of endogenous cannabinoid signaling in energy intake,
      we studied the effects of the CB(1) antagonist AM 251 (1.25, 2.5 and 5 mg/kg ip),
      the anandamide membrane transporter inhibitor VDM 11 (10 mg/kg ip), and the CB(1)
      agonists anandamide (1 mg/kg ip), and methanandamide (1 mg/kg ip), on food
      intake. A single administration of the CB(1) antagonist AM 251 significantly
      reduced food intake for a total of 6 days (P<.05). Reductions in food intake
      brought about by AM 251 were accompanied by reductions in weight gain for 6 days
      (P<.05). Contrary to expectations, VDM 11 did not increase food intake in this
      study. Anandamide was also unable to increase food intake; however, the more
      stable agonist methanandamide significantly increased food intake 3 h after
      administration (P<.05). These results support the role of CB(1) receptor
      antagonists in the treatment of obesity and suggest that the anorectic effect of
      AM 251 may last longer than previously reported.

PMID- 15451652
TI  - Contribution of anal scent gland and urinary odorants to mate recognition in the
      ferret.
AB  - Previous research [J. Neurosci. 21 (2001) 5832-5840] showed that ferrets of both
      sexes require olfactory signals to identify opposite-sex mating partners at a
      distance. The present experiments assessed the contributions of anal scent gland
      and urinary odorants to these preferences. Sexually experienced,
      ovohysterectomized female and castrated male ferrets were injected daily with
      estradiol benzoate and testosterone propionate, respectively. When tested in an
      airtight Y-maze, subjects of both sexes preferred to approach volatile odors
      emitted from opposite- versus same-sex stimulus ferrets that were anesthetized
      and placed in the goal boxes, regardless of whether the anal scent glands of
      stimulus ferrets had been surgically removed or left intact. Subjects of each sex
      showed an equal preference to approach volatile odors emitted from anesthetized
      opposite-sex ferrets that were scent-gland intact as opposed to descented. Female
      subjects preferred to approach volatile anal scent gland odorants, as well as
      urinary odorants from male, as opposed to female conspecifics. Male subjects
      preferred to approach volatile anal scents from females versus males; however,
      males showed no preference for female over male urinary odorants. Our results
      suggest that anal scent gland odorants are sufficient, but not required, for mate
      recognition in the ferret. Instead, a combination of body odorants including, but
      not restricted to, those derived from anal scent gland secretions apparently
      underlie olfactory sex discrimination and partner preference in this carnivore.

PMID- 15451653
TI  - Bottle choice tests for oxidized oil in rats.
AB  - Bottle choice tests in rats are useful for the study of fat appetite. However,
      little is known about the feeding behavior of rats toward oxidized oil. In this
      study, 24-h two-bottle choice tests were performed in male Sprague-Dawley (SD)
      rats for 5 days. When rats were given a choice between thermally oxidized oil and
      fresh oil, they ingested more fresh oil. A choice test between vapor-added fresh
      oil and fresh oil showed that rancid flavor is involved in the avoidance of
      oxidized oil. Results with deodorized oxidized oil indicated that a nonvolatile
      product also influenced choice. In conclusion, rats could distinguish oxidized
      oil from fresh oil and preferred fresh oil.

PMID- 15451654
TI  - Accelerated senescence prone mouse-8 shows early onset of deficits in spatial
      learning and memory in the radial six-arm water maze.
AB  - Available data indicate that the senescence-accelerated prone mouse 8 (SAMP8) is
      an appropriate model of brain aging, with impairments in nonspatial learning and
      memory beginning as early as 2 months of age, and spatial learning and memory
      deficiencies not becoming apparent until after 4 months of age. However, with
      other strains (e.g., C57BL mice), the impairment in spatial memory was found
      earlier than that in nonspatial memory. We considered the possibility that the
      observed differences could be due to strain-specific differences in the training
      equipment. In the present study, a new optimized testing apparatus-the radial six
      arm water maze (RAWM)-for detecting spatial learning and memory in mice, was
      employed, to determine whether there is impairment of spatial learning and memory
      in young SAMP8. The relationship between the spatial learning measures observed
      with the RAWM and the Morris maze, a classic spatial learning and memory testing
      apparatus, was also explored. It was found that, in the RAWM, rather than in the
      Morris maze, the impairment in spatial learning could be measured in SAMP8 mice
      as early as 3 months old, and the impairment in spatial memory in SAMP8 mice aged
      5 months. These results suggested that the spatial learning and memory
      deficiencies could be found in early life of SAMP8 mice, and that RAWM and Morris
      maze each detect different aspects of spatial learning and memory.

PMID- 15451655
TI  - Effects of etifoxine on stress-induced hyperthermia, freezing behavior and
      colonic motor activation in rats.
AB  - Anxiety disorders are often associated with autonomic symptoms, including heart
      palpitations, sweating, elevation of body temperature and alterations of
      gastrointestinal motility. Some of the alterations observed in animals exposed to
      stress are analogous to changes in a number of physiological and endocrine
      parameters observed in anxious patients. With the purpose to guide further
      clinical studies in subtypes of anxious patients, etifoxine, a nonbenzodiazepine
      anxiolytic compound, was evaluated in two rat models of anxiety with measures of
      physiological manifestations: stress-induced hyperthermia (SIH) and conditioned
      fear-stress-induced freezing behavior and activation of colonic motility. The
      sequential handling of animals induced a rise in body temperature attenuated by
      etifoxine (50 mg/kg IP). The emotional stress induced by fear to receive electric
      foot shocks is accompanied by freezing behavior and an increase of the frequency
      of ceco-colonic spike bursts: both parameters were reduced by etifoxine (25-50
      mg/kg IP), independently of changes in pain perception and memory-related
      processes. In response to a stressful event, the stimulation of the corticotropin
      releasing hormone (CRH) system is probably involved in the observed modifications
      of body temperature and colonic motility. It is hypothesized that stress-induced
      CRH activation is attenuated by the enhancement of the inhibitory GABAergic
      system activity associated with etifoxine. These findings will guide future
      evaluation of etifoxine in the treatment of selected anxious patients with
      altered autonomic symptomatology.

PMID- 15451656
TI  - Depressive symptoms and taste reactivity in humans.
AB  - Animal studies suggest that induction of depression-like states may alter
      preference for sweet tastants. A major goal of the present study was to search
      for correlations between depressive symptoms measured by the Beck Depression
      Inventory (BDI) and taste responses to sweet and bitter substances. Thirty-three
      nonclinical volunteers rated intensity and pleasantness of chocolate and vanilla
      milk as well as of sucrose- and quinine-soaked filter paper disks. Reactivity to
      citric acid (sour) and sodium chloride (salty) was also tested with the paper
      disk methodology. Taste detection thresholds were assessed by means of
      electrogustometry. A weak inverse relationship was found between the BDI scores
      (range: 3-33) and rated intensity of paper disks soaked in 60% sucrose. No
      correlations were found between depressive symptoms and intensity, pleasantness
      or identification of the other samples. Similarly, there was no relationship
      between the BDI scores and responses to chocolate and vanilla milk. BDI scores
      were not associated with electrogustometric thresholds. These data suggest that
      depressive symptoms may not influence taste reactivity in nonclinical population.

PMID- 15451657
TI  - Shy and bold great tits (Parus major): body temperature and breath rate in
      response to handling stress.
AB  - A standard handling protocol was used to test the hypothesis that boldness
      predicts stress responsiveness in body temperature and breath rate. Great tit
      (Parus major) nestlings were taken from the field, hand reared until
      independence, and their response to a novel object was assessed. At the age of 6
      months, during the active phase (daytime), body temperature was recorded and
      breath rate was counted immediately after capture and after 5 min of quiet rest
      in a bag. A second group of birds of two lines bidirectionally selected for the
      same trait was tested during the inactive phase (nighttime). During the active
      phase, body temperature and breath rate were higher in the first than in the
      second measurement. In the second measurement, shy individuals showed higher body
      temperature than bold individuals. In the inactive phase, values of both
      parameters were lower than in the active phase. Body temperature was lower in the
      first measurement than in the second measurement and no line difference emerged.
      Breath rate was higher in shy than in bold individuals and did not differ between
      the two measurements. Females had higher body temperatures than males, probably
      due to their lower weight, because body temperature was negatively correlated
      with body mass. The results indicate that body temperature and breath rate are
      indicators of acute stress in songbirds and that differences in personality
      traits during the juvenile phase are reflected in differential stress
      responsiveness later in life.

PMID- 15451658
TI  - Thermal dependence of chemical assessment of predation risk affects the ability
      of wall lizards, Podarcis muralis, to avoid unsafe refuges.
AB  - Prey often respond to predators by increasing refuge use, but some refuges may
      expose prey to other types of predators. Because predators are not always visible
      inside refuges, their chemical stimuli may provide early warning of their
      presence. However, in ectotherms, chemosensory detection of predators may be
      thermally dependent. Lizards often hide in cold refuges, where their body
      temperature (Tb) may decrease, and this might affect their ability to detect
      chemicals of saurophagous snakes that ambush inside refuges. We examined the
      effects of Tb of wall lizards, Podarcis muralis, on their ability to detect
      chemicals of smooth snakes, Coronella austriaca. Differential tongue flick (TF)
      rates and behavioral patterns of lizards in response to scent of smooth snakes
      showed that lizards with optimal Tb discriminated and avoided the snake's scent,
      whereas lizards with suboptimal Tb did not. We also examined the importance of
      this effect on movement patterns and refuge use by lizards in terraria with safe
      (odorless) or unsafe refuges (snake-scented). While results of this experiment
      were variable, there was evidence of snake avoidance in that lizards at optimal
      Tb spent less time in snake-scented refuges relative to odorless refuges.
      Therefore, this study provides evidence that chemosensory discrimination of snake
      chemicals is thermally dependent, and, thus, suboptimal Tb impedes a lizard's
      ability to avoid snake-scented refuges.

PMID- 15451659
TI  - Predominance of clockwise swimming during rest in Southern Hemisphere dolphins.
AB  - Observations on eight bottlenose dolphins located in the Southern Hemisphere
      during rest indicated that they spent the majority of the time (85%) engaged in
      behaviors that can be considered clockwise. This is in contrast with many
      observations of sleeping/resting dolphins in the Northern Hemisphere that spend
      the majority of their time involved in counterclockwise activity. This
      observation leads to the possibility that the reason for preferential swimming
      biases in dolphins is the result of global forces rather than the result of the
      anatomy of the individual dolphins. Our observations also indicate that dolphins
      change overt behavior every 40 s, coincident with the respiration rate. The
      possibility is suggested that the salience of neural activity controlling
      respiration in the reticular system may effect/disrupt reticular attentional
      mechanisms, thus leading to the changes in overt behavior. It is hypothesized
      that this 40-s period may represent the possible attention span of the sleeping
      bottlenose dolphin.

PMID- 15451660
TI  - The crystal structure of a proliferation-inducing ligand, APRIL.
AB  - A proliferation-inducing ligand (APRIL) is a TNF-like cytokine that stimulates
      tumor cell growth. Within the TNF ligand superfamily, APRIL is most similar to B
      cell activation factor (BAFF) with which it shares 30% sequence identity. APRIL
      binds the receptors B-cell maturation antigen (BCMA) and TACI with high affinity;
      both of these receptors have also been shown to bind BAFF, although BCMA has
      significantly higher affinity for APRIL than BAFF. Determination of the crystal
      structure of APRIL from three crystallization conditions at resolutions of 1.8
      2.4A over a pH range from 5.0 to 8.5 reveals a compact trimeric ligand with a
      backbone fold very similar to that of BAFF (1.1A RMSD over 122 structurally
      equivalent Calpha atoms), with the exception of differences in the AA' and DE
      loop regions. Whereas BAFF has been shown to form 20-trimer assemblies under
      certain conditions, the molecular determinants required for BAFF-like assemblies
      are absent in the APRIL structure. No crystal packing suggestive of the formation
      of higher-order assemblies is seen in any of the crystal forms nor does the
      structure vary significantly between pH 5.0 and 8.5. Modeling of the APRIL-BCMA
      complex shows the resulting interface is in agreement with mutagenesis data.

PMID- 15451661
TI  - An allosteric model for transmembrane signaling in bacterial chemotaxis.
AB  - Bacteria are able to sense chemical gradients over a wide range of
      concentrations. However, calculations based on the known number of receptors do
      not predict such a range unless receptors interact with one another in a
      cooperative manner. A number of recent experiments support the notion that this
      remarkable sensitivity in chemotaxis is mediated by localized interactions or
      crosstalk between neighboring receptors. A number of simple, elegant models have
      proposed mechanisms for signal integration within receptor clusters. What is a
      lacking is a model, based on known molecular mechanisms and our accumulated
      knowledge of chemotaxis, that integrates data from multiple, heterogeneous
      sources. To address this question, we propose an allosteric mechanism for
      transmembrane signaling in bacterial chemotaxis based on the "trimer of dimers"
      model, where three receptor dimers form a stable complex with CheW and CheA. The
      mechanism is used to integrate a diverse set of experimental data in a consistent
      framework. The main predictions are: (1) trimers of receptor dimers form the
      building blocks for the signaling complexes; (2) receptor methylation increases
      the stability of the active state and retards the inhibition arising from ligand
      bound receptors within the signaling complex; (3) trimer of dimer receptor
      complexes aggregate into clusters through their mutual interactions with CheA and
      CheW; (4) cooperativity arises from neighboring interaction within these
      clusters; and (5) cluster size is determined by the concentration of receptors,
      CheA, and CheW. The model is able to explain a number of seemingly contradictory
      experiments in a consistent manner and, in the process, explain how bacteria are
      able to sense chemical gradients over a wide range of concentrations by
      demonstrating how signals are integrated within the signaling complex.

PMID- 15451663
TI  - Variation of the acceptor-anticodon interstem angles among mitochondrial and non
      mitochondrial tRNAs.
AB  - A cloverleaf secondary structure and the concomitant "L"-shaped tertiary
      conformation are considered the paradigm for tRNA structure, since there appears
      to be very little deviation from either secondary or tertiary structural forms
      among the more than one dozen canonical (cloverleaf) tRNAs that have yielded to
      crystallographic structure determination. However, many metazoan mitochondrial
      tRNAs deviate markedly from the canonical secondary structure, and are often
      highly truncated (i.e. missing either a dihydrouridine or a TPsiC arm). These
      departures from the secondary cloverleaf form call into question the universality
      of the tertiary (L-shaped) conformation, suggesting that other structural
      constraints may be at play for the truncated tRNAs. To examine this issue, a set
      of 11 tRNAs, comprising mitochondrial and non-mitochondrial, and canonical and
      non-canonical species, has been examined in solution using the method of
      transient electric birefringence. Apparent interstem angles have been determined
      for each member of the set, represented as transcripts in which the anticodon and
      acceptor stems have each been extended by approximately 70 bp of duplex RNA
      helix. The measurements demonstrate much more variation in global structure than
      had been supposed on the basis of crystallographic analysis of canonical tRNAs.
      In particular, the apparent acceptor-anticodon interstem angles are more obtuse
      for the metazoan mitochondrial tRNAs that are truncated (missing either a
      dihydrouridine or a TPsiC arm) than for the canonical (cloverleaf) tRNAs.
      Furthermore, the magnesium dependence of this interstem angle differs for the set
      of truncated tRNAs compared to the canonical species.

PMID- 15451662
TI  - Crystallographic structure of the nuclease domain of 3'hExo, a DEDDh family
      member, bound to rAMP.
AB  - A human 3'-5'-exoribonuclease (3'hExo) has recently been identified and shown to
      be responsible for histone mRNA degradation. Functionally, 3'hExo and a stem-loop
      binding protein (SLBP) target opposite faces of a unique highly conserved stem
      loop RNA scaffold towards the 3' end of histone mRNA, which is composed of a 6 bp
      stem and a 4 nt loop, followed by an ACCCA sequence. Its Caenorhabditis elegans
      homologue, ERI-1, has been shown to degrade small interfering RNA in vitro and to
      function as a negative regulator of RNA interference in neuronal cells. We have
      determined the structure of the nuclease domain (Nuc) of 3'hExo complexed with
      rAMP in the presence of Mg2+ at 1.6 A resolution. The Nuc domain adopts an
      alpha/beta globular fold, with four acidic residues coordinating a binuclear
      metal cluster within the active site, whose topology is related to DEDDh
      exonuclease family members, despite a very low level of primary sequence
      identity. The two magnesium cations in the Nuc active site are coordinated to
      D134, E136, D234 and D298, and together with H293, which can potentially act as a
      general base, provide a platform for hydrolytic cleavage of bound RNA in the 3' -
      > 5' direction. The bound rAMP is positioned within a deep active-site pocket,
      with its purine ring close-packed with the hydrophobic F185 and L189 side-chains
      and its sugar 2'-OH and 3'-OH groups hydrogen bonded to backbone atoms of Nuc.
      There are striking similarities between the active sites of Nuc and epsilon186,
      an Escherichia coli DNA polymerase III proofreading domain, providing a common
      hydrolytic cleavage mechanism for RNA degradation and DNA editing, respectively.

PMID- 15451664
TI  - DNA-looping by RXR tetramers permits transcriptional regulation "at a distance".
AB  - RXR, a member of the superfamily of nuclear hormone receptors, regulates gene
      transcription in response to 9-cis-retinoic acid. We previously showed that,
      among nuclear receptors, RXR is unique in that it self-associates into
      homotetramers, and that these tetramers dissociate rapidly upon ligation. Here,
      we report that binding of RXR tetramers to DNA containing two RXR response
      elements results in a dramatic DNA-looping. RXR can thus juxtapose distant DNA
      sequences, enabling transcriptional regulation by far-upstream factors. We show
      that RXR functions as a DNA architectural factor and that, while this activity is
      regulated by 9-cis-retinoic acid, it is distinct from and independent of the
      receptor's intrinsic transcriptional activity. The data establish RXR as the
      first identified architectural factor whose activity is regulated by a small
      ligand, and demonstrate a novel mechanism of transcriptional regulation by
      retinoids.

PMID- 15451665
TI  - Thermodynamics of DNA binding and distortion by the hyperthermophile chromatin
      protein Sac7d.
AB  - Sac7d is a hyperthermophile chromatin protein which binds non-specifically to the
      minor groove of duplex DNA and induces a sharp kink of 66 degrees with
      intercalation of valine and methionine side-chains. We have utilized the thermal
      stability of Sac7d and the lack of sequence specificity to define the
      thermodynamics of DNA binding over a wide temperature range. The binding affinity
      for poly(dGdC) was moderate at 25 degrees C (Ka = 3.5(+/-1.6) x 10(6) M(-1)) and
      increased by nearly an order of magnitude from 10 degrees C to 80 degrees C. The
      enthalpy of binding was unfavorable at 25 degrees C, and decreased linearly from
      5 degrees C to 60 degrees C. A positive binding heat at 25 degrees C is
      attributed in part to the energy of distorting DNA, and ensures that the
      temperature of maximal binding affinity (75.1+/-5.6 degrees C) is near the growth
      temperature of Sulfolobus acidocaldarius. Truncation of the two intercalating
      residues to alanine led to a decreased ability to bend and unwind DNA at 25
      degrees C with a small decrease in binding affinity. The energy gained from
      intercalation is slightly greater than the free energy penalty of bending duplex
      DNA. Surprisingly, reduced distortion from the double alanine substitution did
      not lead to a significant decrease in the heat of binding at 25 degrees C. In
      addition, an anomalous positive DeltaCp of binding was observed for the double
      alanine mutant protein which could not be explained by the change in polar and
      apolar accessible surface areas. Both the larger than expected binding enthalpy
      and the positive heat capacity can be explained by a temperature dependent
      structural transition in the protein-DNA complex with a Tm of 15-20 degrees C and
      a DeltaH of 15 kcal/mol. Data are discussed which indicate that the endothermic
      transition in the complex is consistent with DNA distortion.

PMID- 15451666
TI  - Ubiquitin-dependent degradation of Id1 and Id3 is mediated by the COP9
      signalosome.
AB  - Recently, evidence is accumulating pointing to a function of the COP9 signalosome
      (CSN) in regulation of ubiquitination by specific ubiquitin ligases. Here, we
      demonstrate by mammalian two-hybrid analysis that the transcriptional regulators
      and substrates of the ubiquitin system Id1 and Id3, but not Id2 and Id4, bind to
      the CSN subunit CSN5. Pull-down experiments revealed that Id3 physically
      interacts with the CSN complex. Additional far Western and pull-down studies with
      Id3 support our two-hybrid data and show that the transcription regulator can
      bind to CSN5 and CSN7. Recombinant Id3 is not phosphorylated by the CSN
      associated kinases CK2 and PKD. However, it inhibits c-Jun and CSN2
      phosphorylation by the isolated CSN complex and by the recombinant CK2. The
      inhibitors of CSN associated kinases, curcumin and emodin, significantly induce
      ubiquitination and proteasome-dependent degradation of transiently expressed Id3
      in HeLa cells. Proteasome-dependent degradation of endogenous Id1 in HeLa cells
      is also stimulated by treatment with curcumin or emodin. Ubiquitination of Id3 is
      shown directly by cotransfection of HeLa cells with Id3 and His-ubiquitin cDNA.
      Curcumin increased Id3-ubiquitin conjugate formation, as shown by Western
      blotting and His-pull-downs. In addition, overexpression of CSN2 leads to
      stabilization of Id3 protein. On the basis of these data, it is speculated that
      CSN-mediated phosphorylation inhibits ubiquitination of Id1 and Id3.

PMID- 15451667
TI  - DNA binding and bending by HMG boxes: energetic determinants of specificity.
AB  - To clarify the physical basis of DNA binding specificity, the thermodynamic
      properties and DNA binding and bending abilities of the DNA binding domains
      (DBDs) of sequence-specific (SS) and non-sequence-specific (NSS) HMG box proteins
      were studied with various DNA recognition sequences using micro-calorimetric and
      optical methods. Temperature-induced unfolding of the free DBDs showed that their
      structure does not represent a single cooperative unit but is subdivided into two
      (in the case of NSS DBDs) or three (in the case of SS DBDs) sub-domains, which
      differ in stability. Both types of HMG box, most particularly SS, are partially
      unfolded even at room temperature but association with DNA results in
      stabilization and cooperation of all the sub-domains. Binding and bending
      measurements using fluorescence spectroscopy over a range of ionic strengths,
      combined with calorimetric data, allowed separation of the electrostatic and non
      electrostatic components of the Gibbs energies of DNA binding, yielding their
      enthalpic and entropic terms and an estimate of their contributions to DNA
      binding and bending. In all cases electrostatic interactions dominate non
      electrostatic in the association of a DBD with DNA. The main difference between
      SS and NSS complexes is that SS are formed with an enthalpy close to zero and a
      negative heat capacity effect, while NSS are formed with a very positive enthalpy
      and a positive heat capacity effect. This indicates that formation of SS HMG box
      DNA complexes is specified by extensive van der Waals contacts between apolar
      groups, i.e. a more tightly packed interface forms than in NSS complexes. The
      other principal difference is that DNA bending by the NSS DBDs is driven almost
      entirely by the electrostatic component of the binding energy, while DNA bending
      by SS DBDs is driven mainly by the non-electrostatic component. The basic
      extensions of both categories of HMG box play a similar role in DNA binding and
      bending, making solely electrostatic interactions with the DNA.

PMID- 15451669
TI  - Apo and inhibitor complex structures of BACE (beta-secretase).
AB  - Human BACE, also known as beta-secretase, shows promise as a potential
      therapeutic target for Alzheimer's disease. We determined the apo structure of
      BACE to 1.75 A, and a structure of a hydroxyethylamine inhibitor complex derived
      by soaking. These show significant active-site movements compared to previously
      described BACE structures. Additionally, the structures reveal two pockets that
      could be targeted by structure-based drug design.

PMID- 15451668
TI  - The structure and ligand binding properties of the B. subtilis YkoF gene product,
      a member of a novel family of thiamin/HMP-binding proteins.
AB  - The crystal structure of the Bacillus subtilis YkoF gene product, a protein
      involved in the hydroxymethyl pyrimidine (HMP) salvage pathway, was solved by the
      multiwavelength anomalous dispersion (MAD) method and refined with data extending
      to 1.65 A resolution. The atomic model of the protein shows a homodimeric
      association of two polypeptide chains, each containing an internal repeat of a
      ferredoxin-like betaalphabetabetaalphabeta fold, as seen in the ACT and RAM
      domains. Each repeat shows a remarkable similarity to two members of the COG0011
      domain family, the MTH1187 and YBL001c proteins, the crystal structures of which
      were recently solved by the Northeast Structural Genomics Consortium. Two YkoF
      monomers form a tightly associated dimer, in which the amino acid residues
      forming the interface are conserved among family members. A putative small-ligand
      binding site was located within each repeat in a position analogous to the serine
      binding site of the ACT-domain of the Escherichia coli phosphoglycerate
      dehydrogenase. Genetic data suggested that this could be a thiamin or HMP-binding
      site. Calorimetric data confirmed that YkoF binds two thiamin molecules with
      varying affinities and a thiamine-YkoF complex was obtained by co
      crystallization. The atomic model of the complex was refined using data to 2.3 A
      resolution and revealed a unique H-bonding pattern that constitutes the molecular
      basis of specificity for the HMP moiety of thiamin.

PMID- 15451670
TI  - Crystallographic analysis of CaaX prenyltransferases complexed with substrates
      defines rules of protein substrate selectivity.
AB  - Post-translational modifications are essential for the proper function of many
      proteins in the cell. The attachment of an isoprenoid lipid (a process termed
      prenylation) by protein farnesyltransferase (FTase) or geranylgeranyltransferase
      type I (GGTase-I) is essential for the function of many signal transduction
      proteins involved in growth, differentiation, and oncogenesis. FTase and GGTase-I
      (also called the CaaX prenyltransferases) recognize protein substrates with a C
      terminal tetrapeptide recognition motif called the Ca1a2X box. These enzymes
      possess distinct but overlapping protein substrate specificity that is determined
      primarily by the sequence identity of the Ca1a2X motif. To determine how the
      identity of the Ca1a2X motif residues and sequence upstream of this motif affect
      substrate binding, we have solved crystal structures of FTase and GGTase-I
      complexed with a total of eight cognate and cross-reactive substrate peptides,
      including those derived from the C termini of the oncoproteins K-Ras4B, H-Ras and
      TC21. These structures suggest that all peptide substrates adopt a common binding
      mode in the FTase and GGTase-I active site. Unexpectedly, while the X residue of
      the Ca1a2X motif binds in the same location for all GGTase-I substrates, the X
      residue of FTase substrates can bind in one of two different sites. Together,
      these structures outline a series of rules that govern substrate peptide
      selectivity; these rules were utilized to classify known protein substrates of
      CaaX prenyltransferases and to generate a list of hypothetical substrates within
      the human genome.

PMID- 15451671
TI  - The P23T cataract mutation causes loss of solubility of folded gammaD-crystallin.
AB  - Mutations in the human gammaD-crystallin gene have been linked to several types
      of congenital cataracts. In particular, the Pro23 to Thr (P23T) mutation of human
      gammaD crystallin has been linked to cerulean, lamellar, coralliform, and
      fasciculiform congenital cataracts. We have expressed and purified wild-type
      human gammaD, P23T, and the Pro23 to Ser23 (P23S) mutant. Our measurements show
      that P23T is significantly less soluble than wild-type human gammaD, with P23S
      having an intermediate solubility. Using synchrotron radiation circular dichroism
      spectroscopy, we have determined that the P23T mutant has a slightly increased
      content of beta-sheet, which may be attributed to the extension of an edge beta
      strand due to the substitution of Pro23 with a residue able to form hydrogen
      bonds. Neither of the point mutations appears to have reduced the thermal
      stability of the protein significantly, nor its resistance to guanidine
      hydrochloride-induced unfolding. These results suggest that insolubility, rather
      than loss of stability, is the primary basis for P23T congenital cataracts.

PMID- 15451672
TI  - A domain in the N-terminal part of Hsp26 is essential for chaperone function and
      oligomerization.
AB  - Small heat-shock proteins (Hsps) are ubiquitous molecular chaperones which
      prevent the unspecific aggregation of non-native proteins. For Hsp26, a cytosolic
      sHsp from of Saccharomyces cerevisiae, it has been shown that, at elevated
      temperatures, the 24 subunit complex dissociates into dimers. This dissociation
      is required for the efficient interaction with non-native proteins. Deletion
      analysis of the protein showed that the N-terminal half of Hsp26 (amino acid
      residues 1-95) is required for the assembly of the oligomer. Limited proteolysis
      in combination with mass spectrometry suggested that this region can be divided
      in two parts, an N-terminal segment including amino acid residues 1-30 and a
      second part ranging from residues 31-95. To analyze the structure and function of
      the N-terminal part of Hsp26 we created a deletion mutant lacking amino acid
      residues 1-30. We show that the oligomeric state and the structure, as determined
      by size exclusion chromatography and electron microscopy, corresponds to that of
      the Hsp26 wild-type protein. Furthermore, this truncated version of Hsp26 is
      active as a chaperone. However, in contrast to full length Hsp26, the truncated
      version dissociates at lower temperatures and complexes with non-native proteins
      are less stable than those found with wild-type Hsp26. Our results suggest that
      the N-terminal segment of Hsp26 is involved in both, oligomerization and
      chaperone function and that the second part of the N-terminal region (amino acid
      residues 31-95) is essential for both functions.

PMID- 15451673
TI  - Structural and functional analysis of the C-terminal cytoplasmic domain of FlhA,
      an integral membrane component of the type III flagellar protein export apparatus
      in Salmonella.
AB  - FlhA is an integral membrane component of the Salmonella type III flagellar
      protein export apparatus. It consists of 692 amino acid residues and has two
      domains: the N-terminal transmembrane domain consisting of the first 327 amino
      acid residues, and the C-terminal cytoplasmic domain (FlhAC) comprising the
      remainder. Here, we have investigated the structure and function of FlhAC. DNA
      sequence analysis revealed that temperature-sensitive flhA mutations, which
      abolish flagellar protein export at the restrictive temperature, lie in FlhAC,
      indicating that FlhAC plays an important role in the protein export process.
      Limited proteolysis of purified His-FlhAC by trypsin and V8 showed that only a
      small part of FlhAC near its N terminus (residues 328-351) is sensitive to
      proteolysis. FlhAC38K, the smallest fragment produced by V8 proteolysis, is
      monomeric and has a spherical shape as judged by analytical gel filtration
      chromatography and analytical ultracentrifugation. The far-UV CD spectrum of
      FlhAC38K showed that it contains considerable amounts of secondary structure.
      FlhA(Delta328-351) missing residues 328-351 failed to complement the flhA mutant,
      indicating that the proteolytically sensitive region of FlhA is important for its
      function. FlhA(Delta328-351) was inserted into the cytoplasmic membrane, and
      exerted a strong dominant negative effect on wild-type cells, suggesting that it
      retains the ability to interact with other export components within the
      cytoplasmic membrane. Overproduced FlhAC38K inhibited both motility and flagellar
      protein export of wild-type cells to some degree, suggesting that FlhAC38K is
      directly involved in the translocation reaction. Amino acid residues 328-351 of
      FlhA appear to be a relatively flexible linker between the transmembrane domain
      and FlhAC38K.

PMID- 15451674
TI  - Raman optical activity demonstrates poly(L-proline) II helix in the N-terminal
      region of the ovine prion protein: implications for function and misfunction.
AB  - The aqueous solution structure of the full-length recombinant ovine prion protein
      PrP(25-233), together with that of the N-terminal truncated version PrP(94-233),
      have been studied using vibrational Raman optical activity (ROA) and ultraviolet
      circular dichroism (UVCD). A sharp positive band at approximately 1315 cm(-1)
      characteristic of poly(L-proline) II (PPII) helix that is present in the ROA
      spectrum of the full-length protein is absent from that of the truncated protein,
      together with bands characteristic of beta-turns. Although it is not possible
      similarly to identify PPII helix in the full-length protein directly from its
      UVCD spectrum, subtraction of the UVCD spectrum of PrP(94-233) from that of
      PrP(25-233) yields a difference UVCD spectrum also characteristic of PPII
      structure and very similar to the UVCD spectrum of murine PrP(25-113). These
      results provide confirmation that a major conformational element in the N
      terminal region is PPII helix, but in addition show that the PPII structure is
      interspersed with beta-turns and that little PPII structure is present in PrP(94
      233). A principal component analysis of the ROA data indicates that the alpha
      helix and beta-sheet content, located in the structured C-terminal domain, of the
      full-length and truncated proteins are similar. The flexibility imparted by the
      high PPII content of the N-terminal domain region may be an essential factor in
      the function and possibly also the misfunction of prion proteins.

PMID- 15451675
TI  - Crystal structures and electron micrographs of fungal volvatoxin A2.
AB  - Membrane adhesion and insertion of protein are essential to all organisms, but
      the underlying mechanisms remain largely unknown. Membrane pore-forming toxins
      (PFTs) are potential model systems for studying these mechanisms. We have
      determined the crystal structures of volvatoxin A2 (VVA2), a fungal PFT from
      Volvariella volvacea, using Br-multiple-wavelength anomalous diffraction (MAD).
      The VVA2 structures obtained at pH 4.6, pH 5.5 and pH 6.5 were refined to
      resolutions of 1.42 A, 2.6 A and 3.2 A, respectively. The structures reveal that
      the VVA2 monomer contains a single alpha/beta domain. Most of the VVA2 surface is
      occupied by its oligomerization motif and two putative heparin-binding motifs.
      Residues Ala91 to Ala101 display several conformations at different pH values,
      which might be under the control of His87. We also found that the shape of one
      putative heparin-binding motif in VVA2 appears similar to those found in
      fibroblast growth factors, and the other one displays a linear polypeptide. Our
      results suggest several possible intermediates of protein assembly in solution
      and protein adhering to cell membranes before conformational changes. The
      electron micrographs of VVA2 molecules in solution, at a protein concentration of
      1 microg ml(-1), show that they can assemble into filament-like or braid-like
      oligomers in a pH-dependent way. In addition, the arc-shaped VVA2 structure
      obtained at pH 6.5 suggests that VVA2 could form a two-layered helical oligomer
      with 18 subunits per turn. The structures presented here could be used to
      elucidate the pore-formation mechanisms of VVA2 and its structural neighbors, Cyt
      toxins from Bacillus thuringiensis.

PMID- 15451676
TI  - Structural determinants of proton blockage in aquaporins.
AB  - Aquaporins are an important class of membrane channels selective for water and
      linear polyols but impermeable to ions, including protons. Recent computational
      studies have revealed that the relay of protons through the water-conduction
      pathway of aquaporin channels is opposed by a substantial free energy barrier
      peaking at the signature NPA motifs. Here, free-energy simulations and continuum
      electrostatic calculations are combined to examine the nature and the magnitude
      of the contribution of specific structural elements to proton blockage in the
      bacterial glycerol uptake facilitator, GlpF. Potential of mean-force profiles for
      both hop and turn steps of structural diffusion in the narrow pore are obtained
      for artificial variants of the GlpF channel in which coulombic interactions
      between the pore contents and conserved residues Asn68 and Asn203 at the NPA
      signature motifs, Arg206 at the selectivity filter, and the peptidic backbone of
      the two half-helices M3 and M7, which are arranged in head-to-head fashion around
      the NPA motifs, are turned off selectively. A comparison of these results with
      electrostatic energy profiles for the translocation of a probe cation throughout
      the water permeation pathway indicates that the free-energy profile for proton
      movement inside the narrow pore is dominated by static effects arising from the
      distribution of charged and polar groups of the channel, whereas dielectric
      effects contribute primarily to opposing the access of H+ to the pore mouths
      (desolvation penalty). The single most effective way to abolish the free-energy
      gradients opposing the movement of H+ around the NPA motif is to turn off the
      dipole moments of helices M3 and M7. Mutation of either of the two NPA Asn
      residues to Asp compensates for charge-dipole and dipole-dipole effects opposing
      the hop and turn steps of structural diffusion, respectively, and dramatically
      reduces the free energy barrier of proton translocation, suggesting that these
      single mutants could leak protons.

PMID- 15451677
TI  - FRONTLINE--another of the interminable revisitings of Freud's "Analysis
      terminable and interminable".

PMID- 15451678
TI  - A training psychotherapy elective for military psychiatry residents.
AB  - A Training Psychotherapy Elective (TPE) was developed to meet the special
      requirements of military medical education; but the model is generally applicable
      to all psychiatry training programs. It aims to demonstrate the technique of
      individual medical psychotherapy by offering residents and fellows an experience
      of this procedure in a patient role. It affords trainees an opportunity to
      address healthy curiosities about their mental functioning without the
      requirement of endorsing a complaint related to a mental disorder. Training
      psychotherapy follows the technical model that residents learn in their
      outpatient rotations. Transparent interventions allow trainees both to experience
      the impact of clarification and interpretation and to see how the therapist
      derived them from their associations. This facilitates the application of these
      interventions to work with patients. It also affords trainees an emotionally
      sheltered environment in which to explore attitudes and concerns associated with
      their service in military operations, fostering readiness for such assignments.

PMID- 15451679
TI  - Trigger and screen: shame dynamics and the problem of instigation in Freud's
      dreams.
AB  - This paper concerns the problem of instigation, that is to say, the dynamic
      triggering, of the dream in Freud's "The Interpretation of Dreams" (1900)/1953).
      The problem of instigation came to the author's attention in the course of
      studying treatment difficulties and failures outside of the psychoanalytic
      situation, specifically the dynamics of impulsive actions and of posttraumatic
      nightmares, which the author then used in the consideration of problems
      associated with conceptualizing instigation in "The Interpretation of Dreams."
      Instigatory dynamics other than Freud's metaphor of "capitalist and entrepreneur"
      have attracted scant attention; and that metaphor as Freud applied it is an
      incomplete example of the instigatory process since its theoretical formulation
      are discrepant with Freud's clinical sensitivity to the instigation of his own
      dreams. Four of Freud's major dreams reveal an instigatory experience consisting
      of a contemporaneous ego-ideal conflict due to an anticipation of professional
      status as denied or lost. This contemporaneous ego-ideal conflict resonates with
      early and unconscious shame dynamics and shame fantasies involving tension from
      the ego-ideal that result from Freud's seeing himself as relegated to inferior or
      asexual status. The wish to possess an object of desire was not primary in any of
      these dreams. The complex nexus of shame dynamics, in turn, instigates more
      visible competitive wishes; these strive to alter the circumstances that threaten
      to give rise to shame or turn the tables on the shamer. The instigating shame
      dynamics are thus screened by the more visible dynamics of hostile competition.
      This formulation offers an expanded view of the dynamics of instigation which
      leads to a more balanced understanding of the nature and components of
      instigatory shame dynamics and their relationship to the dynamics of conflicts
      involving hostility, competition, and guilt.

PMID- 15451680
TI  - Violence: innate or acquired? A survey and some opinions.
AB  - Freud's psychoanalysis and Lorenz's ethology consider human aggressiveness to be
      innate. According to recent archaeological excavations and evolutionary studies,
      human groups in the Upper Paleolithic and Early Neolithic were peaceful and
      cooperative. This culture was replaced ten thousand years ago by a predatory
      hierarchical structure, which is here viewed as a cultural variant.

PMID- 15451681
TI  - The place of erotic transference and countertransference in clinical practice.
AB  - Patients who express intense, erotic attraction to their therapists pose special
      treatment challenges that may not respond well to the interpretative effects of
      the therapist. The wish that the therapist demonstrate love for the patient and
      the therapists' own erotic feelings toward such patients can create misalliances
      as well difficult technical moments. Furthermore, some patients expressing their
      love for their therapist may have physiological manifestations while others would
      not. At the same time, therapists may not experience erotic feelings toward the
      patients' expressions of love. The purpose of this paper is to try to answer the
      following questions: How do we conceptualize our patients' erotic manifestations?
      Are those expressions of Oedipal or preoedipal pathology? What are the
      countertransference reactions of the analyst? Two clinical examples will
      highlight these issues.

PMID- 15451682
TI  - Freud's wife.
AB  - "What do women want?" Sigmund Freud famously declared, yet Martha, his wife for
      over 50 years, has always received scant attention. Most biographies of Freud and
      psychoanalytic studies treat her as an early romantic interest and neglect her
      once she becomes a wife and mother. Still, if Freud's theories on everything from
      domesticity to sexuality were drawn partly from his own experience, Martha's
      personality and her interaction with her husband are significant to the history
      of psychoanalysis. Drawing on biographical, epistolary, and archival material, as
      well as Freud's own writings and the work of psychoanalytic commentators, the
      authors speculate on what roles Martha played and how Freud used her as a
      template upon which he based some of this theories about female behavior.

PMID- 15451683
TI  - Commentary on "Freud's Wife" by David Galef and Harold Galef.

PMID- 15451684
TI  - Repetition compulsion in a trauma victim: is the "analgesia principle" beyond the
      pleasure principle? Clinical implications.
AB  - This paper reviews the concept of repetition compulsion (RC) from Freud's
      original formulation to recent contributions from psychoanalysis and the
      neurosciences. Literature on RC presented four major controversies: (1) Does RC
      describe a broad range of dysfunctional repetitive behaviors, or only the
      repetition of severe traumatic experiences? (2) Is RC an attempt to achieve
      mastery and control of a traumatic experience, or to reach a particular psychic
      state as analgesia or excitement, which reduces the perception of emotional pain?
      (3) Is the death instinct an acceptable explanation for RC? (4) Is RC a useful,
      meaningful, and specific concept? The author describes his personal perspective
      on RC which integrates psychodynamic and biological contributions. Clinical
      material is provided.

PMID- 15451685
TI  - On the nature of psychodynamic science.
AB  - In a previous article (Brookes, 2003), it was suggested that a science devoted to
      the subjective data obtained in psychodynamic therapy would require
      classification of psyche, the object of study, as a hypothetical construct, a
      classic concept in the philosophy of psychological science. The present article
      argues for and outlines a necessarily new and unique scientific paradigm for
      psychodynamics by further suggesting (1) that positivistic science is not
      appropriate to the phenomenological data which psychodynamic concepts explain,
      (2) that retroductive inferences are preferable to inductive or deductive
      inferences in handling such data, (3) that the concept of meaning as scientific
      validation is more suitable to psychodynamic science than are the concepts of
      measurement and operational validation, and (4) that meaningful validation is
      best elaborated through the application of the concepts of erroneous meaning, of
      synchronicity, and of numinosity. These and other ideas are briefly described,
      and will be elaborated further in subsequent papers.

PMID- 15451686
TI  - Elements of dynamics III: the face and the couch.
AB  - In this article the therapeutic and scientific advantages of face-to-face
      psychoanalytic treatment are contrasted with the symbolism, power, and mystery of
      the psychoanalytic couch. Beginning with recent commentary on the meaning of the
      couch, I consider some problems associated with its use, such as regressive
      irretrievability of learning, paucity of affective and empathic connection,
      preservation of shame, and coercive aspects. Compromises between couch and face
      are offered, and more clinical and research focus on facial affective expression
      is encouraged.

PMID- 15451687
TI  - Modelling non-additive and nonlinear signals from climatic noise in ecological
      time series: Soay sheep as an example.
AB  - Understanding how climate can interact with other factors in determining patterns
      of species abundance is a persistent challenge in ecology. Recent research has
      suggested that the dynamics exhibited by some populations may be a non-additive
      function of climate, with climate affecting population growth more strongly at
      high density than at low density. However, we lack methodologies to adequately
      explain patterns in population growth generated as a result of interactions
      between intrinsic factors and extrinsic climatic variation in non-linear systems.
      We present a novel method (the Functional Coefficient Threshold Auto-Regressive
      (FCTAR) method) that can identify interacting influences of climate and density
      on population dynamics from time-series data. We demonstrate its use on count
      data on the size of the Soay sheep population, which is known to exhibit dynamics
      generated by nonlinear and non-additive interactions between density and climate,
      living on Hirta in the St Kilda archipelago. The FCTAR method suggests that
      climate fluctuations can drive the Soay sheep population between different
      dynamical regimes--from stable population size through limit cycles and non
      periodic fluctuations.

PMID- 15451688
TI  - Differences in the timing of reproduction between urban and forest European
      blackbirds (Turdus merula): result of phenotypic flexibility or genetic
      differences?
AB  - Species which have settled in urban environments are exposed to different
      conditions from their wild conspecifics. A previous comparative study of an urban
      and a forest-living European blackbird population had revealed a three weeks
      earlier onset of gonadal growth in urban individuals. These physiological
      adjustments are either the result of genetic differences that have evolved during
      the urbanization process, or of phenotypic flexibility resulting from the bird's
      exposure to the different environmental conditions of town or forest. To identify
      which of these two mechanisms causes the differences in reproductive timing, hand
      reared birds originating from the urban and the forest populations were kept in
      identical conditions. The substantial differences in the timing of reproduction
      between urban and forest birds known from the field did not persist under
      laboratory conditions, indicating that temporal differences in reproductive
      timing between these two populations are mainly a result of phenotypic
      flexibility. Nevertheless, urban males initiated plasma luteinizing hormone (LH)
      secretion and testicular development earlier than forest males in their first
      reproductive season. Moreover, plasma LH concentration and follicle size declined
      earlier in urban females than in forest females, suggesting that genetic
      differences are also involved and might contribute to the variations in the
      timing of reproduction in the wild.

PMID- 15451689
TI  - Crocodyliform biogeography during the Cretaceous: evidence of Gondwanan
      vicariance from biogeographical analysis.
AB  - Explanations of the distributions of terrestrial vertebrates during the Mesozoic
      are currently vigorously contested and debated in palaeobiogeography. Recent
      studies focusing on dinosaurs yield conflicting hypotheses. Dispersal, coupled
      with regional extinction or vicariance driven by continental break-up, have been
      cited as the main causal factors behind dinosaur distributions in the Mesozoic.
      To expand the scope of the debate and test for vicariance within another
      terrestrial group, I herein apply a cladistic biogeographical method to a large
      sample of Cretaceous crocodyliform taxa. A time-slicing methodology is employed
      and a refinement made to account for the divergence times of the analysed clades.
      The results provide statistically significant evidence that Gondwana
      fragmentation affected crocodyliform diversification during the Mid-Late
      Cretaceous. Detection of a vicariant pattern within crocodyliforms is important
      as it helps corroborate vicariance hypotheses in other fossil and extant groups
      as well as furthers the move towards more taxonomically diverse approaches to
      palaeobiogeographical research.

PMID- 15451690
TI  - Evolution of a climbing habit promotes diversification in flowering plants.
AB  - Key innovations are traits that are associated with the particular evolutionary
      'success' of some taxonomic groups. Climbing plants depend on the availability of
      physical support to reach the canopy and thereby prevent shading by neighbouring
      plants. The present article shows that the evolution of a climbing habit in
      flowering plants constitutes a key innovation. A literature survey identified 48
      pairs of sister groups from 45 families of flowering plants for which information
      on phylogenetic relationships, growth habit and species richness was available.
      In 38 cases, the climbing taxa were more diverse than their non-climbing sister
      groups. This pattern was highly significant. The same result was found when
      separate analyses were carried out for herbaceous and woody climbing plants,
      which differ in their constraints for successfully reaching a support.

PMID- 15451691
TI  - Paternal effects on functional gender account for cryptic dioecy in a perennial
      plant.
AB  - Natural selection operates on the mating strategies of hermaphrodites through
      their functional gender, i.e. their relative success as male versus female
      parents. Because functional gender will tend to be strongly influenced by sex
      allocation, it is often estimated in plants by counting seeds and pollen grains.
      However, a plant's functional gender must also depend on the fate of the seeds
      and pollen grains it produces. We provide clear evidence of a paternal effect on
      the functional gender of a plant that is independent of the resources invested in
      pollen. In the Mediterranean tree Fraxinus ornus, males coexist with
      hermaphrodites that disperse viable pollen and that sire seeds; the population
      would thus appear to be functionally androdioecious. However, we found that
      seedlings sired by hermaphrodites grew significantly less well than those sired
      by males, suggesting that hermaphrodites may be functionally less male than they
      seem. The observed 1 : 1 sex ratios in F. ornus, which have hitherto been
      difficult to explain in the light of the seed-siring ability of hermaphrodites,
      support our interpretation that this species is cryptically dioecious. Our
      results underscore the importance of considering progeny quality when estimating
      gender, and caution against inferring androdioecy on the basis of a siring
      ability of hermaphrodites alone.

PMID- 15451692
TI  - Two classes of deleterious recessive alleles in a natural population of
      zebrafish, Danio rerio.
AB  - Natural populations carry deleterious recessive alleles which cause inbreeding
      depression. We compared mortality and growth of inbred and outbred zebrafish,
      Danio rerio, between 6 and 48 days of age. Grandparents of the studied fish were
      caught in the wild. Inbred fish were generated by brother-sister mating.
      Mortality was 9% in outbred fish, and 42% in inbred fish, which implies at least
      3.6 lethal equivalents of deleterious recessive alleles per zygote. There was no
      significant inbreeding depression in the growth, perhaps because the surviving
      inbred fish lived under less crowded conditions. In contrast to alleles that
      cause embryonic and early larval mortality in the same population, alleles
      responsible for late larval and early juvenile mortality did not result in any
      gross morphological abnormalities. Thus, deleterious recessive alleles that
      segregate in a wild zebrafish population belong to two sharply distinct classes:
      early-acting, morphologically overt, unconditional lethals; and later-acting,
      morphologically cryptic, and presumably milder alleles.

PMID- 15451693
TI  - Sire attractiveness influences offspring performance in guppies.
AB  - According to the good-genes hypothesis, females choose among males to ensure the
      inheritance of superior paternal genes by their offspring. Despite increasing
      support for this prediction, in some cases differential (non-genetic) maternal
      effects may obscure or amplify the relationship between paternal attractiveness
      and offspring quality. Artificial insemination controls such effects because it
      uncouples mate choice from copulation, therefore denying females the opportunity
      of assessing male attractiveness. We adopted this technique in the live-bearing
      fish Poecilia reticulata and examined whether paternal coloration was associated
      with the behavioural performance of newborn offspring. Sexually receptive virgin
      females were inseminated with sperm taken individually from donor males that
      exhibited high variation in the area of orange pigmentation, a trait known to
      influence female choice in the study population. Our analysis of offspring
      performance focused on the anti-predator behaviour of newborn fish, including
      schooling by sibling pairs, the response (swimming speed) of these fishes to a
      simulated avian predator, and the time taken for a naive investigator to capture
      the offspring. Although we found no significant effect of sire coloration on
      either schooling or swimming speed, our analysis revealed a significant positive
      association between sire coloration and the ability of newborn offspring to evade
      capture. This finding supports the view that at least one aspect of anti-predator
      behaviour in newborn offspring is influenced by sire genotype, which in turn is
      revealed by the expression of secondary sexual traits.

PMID- 15451694
TI  - Cannabinoid inhibition improves memory in food-storing birds, but with a cost.
AB  - Food-storing birds demonstrate remarkable memory ability in recalling the
      locations of thousands of hidden food caches. Although this behaviour requires
      the hippocampus, its synaptic mechanisms are not understood. Here we show the
      effects of cannabinoid receptor (CB1-R) blockade on spatial memory in food
      storing black-capped chickadees (Poecile atricapilla). Intra-hippocampal
      infusions of the CB1-R antagonist SR141716A enhanced long-term memory for the
      location of a hidden food reward, measured 72 h after encoding. However, when the
      reward location changed during the retention interval, birds that had received
      SR141716A during initial learning showed impairments in recalling the most recent
      reward location. Thus, blocking CB1-R activity may lead to more robust, long
      lasting memories, but these memories may be a source of proactive interference.
      The relationship between trace strength and interference may be important in
      understanding neural mechanisms of hippocampal function in general, as well as
      understanding the enhanced memory of food-storing birds.

PMID- 15451695
TI  - Evolution of mammals: lactation helps mothers to cope with unreliable food
      supplies.
AB  - Lactation is a ubiquitous feature of mammalian reproduction. Because lactating
      females can draw on their nutrient reserves for milk production, it offers
      mothers and their dependent young independence from fluctuations in their food
      supplies. However, converting food to reserves and milk is relatively inefficient
      at delivering nutrients to offspring. We use dynamic programming to contrast the
      performance of mothers that provision dependent, refuge-bound offspring optimally
      from their nutrient reserves with otherwise equivalent mothers that do so
      directly from the food they find. In this way, we demonstrate formally that the
      selective advantage to lactating mothers, who can provision--at a cost--without
      having found food recently, can be substantial with uncertain food supplies and
      few opportunities for future reproduction under a wide range of circumstances.
      Hence, it is likely that unreliability associated with the lifestyles of the
      small, primitive mammal-like reptiles that evolved extended maternal care,
      selected for fully-developed milk production and consumption, prompting the
      evolution of true mammals. Moreover, this work suggests that selection for coping
      with unreliable food access during provisioning may underlie key life-history
      differences between birds and mammals because the mass constraints imposed by
      flight restrict the level of reserves that mothers can carry and provision from.

PMID- 15451696
TI  - Reproductive success in presenescent common gulls (Larus canus): the importance
      of the last year of life.
AB  - Survival selection against individuals of inferior quality (measured as breeding
      success) has been proposed to account for the increase in average reproductive
      success with advancing age in presenescent birds. This so-called selection
      hypothesis relies on quality-dependent survival. In the present breeding
      performance study of common gulls, Larus canus, this assumption was not verified.
      In particular, omitting the last breeding year from the analysis resulted in the
      disappearance of the correlation between breeding success and survival. A
      positive correlation in the full dataset was thus solely based on the poor
      breeding success of ultimate breeders. Indeed, presenescent individuals were
      shown to have a specifically low breeding success in their terminal breeding
      event. The poor success of ultimate breeders thus reflects an abruptly declined
      condition rather than the birds' overall quality. A comparison of the survival of
      poor and good performers, involving last-time breeders, thus needs not to be a
      proper test of the selection hypothesis. Longitudinal analysis revealed a steady
      increase of individual breeding success until the tenth breeding year. The
      results suggest that an increase of breeding success with age often found in
      cross-sectional analyses is primarily a result of age-related improvements of
      competence and/or increased reproductive effort.

PMID- 15451697
TI  - Queen-signal modulation of worker pheromonal composition in honeybees.
AB  - Worker sterility in honeybees is neither absolute nor irreversible. Whether under
      queen or worker control, it is likely to be mediated by pheromones. Queen
      specific pheromones are not exclusive to queens; workers with activated ovaries
      also produce them. The association between ovarian activation and queen-like
      pheromone occurrence suggests the latter as providing a reliable signal of
      reproductive ability. In this study we investigated the effect of queen
      pheromones on ovary development and occurrence of queen-like esters in workers'
      Dufour's gland. Workers separated from the queenright compartment by a double
      mesh behaved like queenless workers, activating their ovaries and expressing a
      queen-like Dufour's gland secretion, confirming that the pheromones regulating
      both systems are non-volatile. Workers with developed ovaries produced
      significantly more secretion than sterile workers, which we attribute primarily
      to increased ester production. Workers separated from the queenright compartment
      by a single mesh displayed a delayed ovarian development, which we attribute to
      interrupted transfer of the non-volatile pheromone between compartments. We
      suggest that worker expression of queen-like characters reflects a queen-worker
      arms race; and that Dufour's gland secretion may provide a reliable signal for
      ovarian activation. The associative nature between ovary development and Dufour's
      gland ester production remains elusive.

PMID- 15451698
TI  - Tuning of Strouhal number for high propulsive efficiency accurately predicts how
      wingbeat frequency and stroke amplitude relate and scale with size and flight
      speed in birds.
AB  - The wing kinematics of birds vary systematically with body size, but we still,
      after several decades of research, lack a clear mechanistic understanding of the
      aerodynamic selection pressures that shape them. Swimming and flying animals have
      recently been shown to cruise at Strouhal numbers (St) corresponding to a regime
      of vortex growth and shedding in which the propulsive efficiency of flapping
      foils peaks (St approximately fA/U, where f is wingbeat frequency, U is cruising
      speed and A approximately bsin(theta/2) is stroke amplitude, in which b is
      wingspan and theta is stroke angle). We show that St is a simple and accurate
      predictor of wingbeat frequency in birds. The Strouhal numbers of cruising birds
      have converged on the lower end of the range 0.2 < St < 0.4 associated with high
      propulsive efficiency. Stroke angle scales as theta approximately 67b-0.24, so
      wingbeat frequency can be predicted as f approximately St.U/bsin(33.5b-0.24),
      with St0.21 and St0.25 for direct and intermittent fliers, respectively. This
      simple aerodynamic model predicts wingbeat frequency better than any other
      relationship proposed to date, explaining 90% of the observed variance in a
      sample of 60 bird species. Avian wing kinematics therefore appear to have been
      tuned by natural selection for high aerodynamic efficiency: physical and
      physiological constraints upon wing kinematics must be reconsidered in this
      light.

PMID- 15451699
TI  - Face pictures reduce behavioural, autonomic, endocrine and neural indices of
      stress and fear in sheep.
AB  - Faces are highly emotive stimuli and we find smiling or familiar faces both
      attractive and comforting, even as young babies. Do other species with
      sophisticated face recognition skills, such as sheep, also respond to the
      emotional significance of familiar faces? We report that when sheep experience
      social isolation, the sight of familiar sheep face pictures compared with those
      of goats or inverted triangles significantly reduces behavioural (activity and
      protest vocalizations), autonomic (heart rate) and endocrine (cortisol and
      adrenaline) indices of stress. They also increase mRNA expression of activity
      dependent genes (c-fos and zif/268) in brain regions specialized for processing
      faces (temporal and medial frontal cortices and basolateral amygdala) and for
      emotional control (orbitofrontal and cingulate cortex), and reduce their
      expression in regions associated with stress responses (hypothalamic
      paraventricular nucleus) and fear (central and lateral amygdala). Effects on face
      recognition, emotional control and fear centres are restricted to the right brain
      hemisphere. Results provide evidence that face pictures may be useful for
      relieving stress caused by unavoidable social isolation in sheep, and possibly
      other animal species, including humans. The finding that sheep, like humans,
      appear to have a right brain hemisphere involvement in the control of negative
      emotional experiences also suggests that functional lateralization of brain
      emotion systems may be a general feature in mammals.

PMID- 15451700
TI  - Facial resemblance increases the attractiveness of same-sex faces more than other
      sex faces.
AB  - Our reactions to facial self-resemblance could reflect either specialized
      responses to cues of kinship or by-products of the general perceptual mechanisms
      of face encoding and mere exposure. The adaptive hypothesis predicts differences
      in reactions to self-resemblance in mating and prosocial contexts, while the by
      product hypothesis does not. Using face images that were digitally transformed to
      resemble participants, I showed that the effects of resemblance on attractiveness
      judgements depended on both the sex of the judge and the sex of the face being
      judged: facial resemblance increased attractiveness judgements of same-sex faces
      more than other-sex faces, despite the use of identical procedures to manipulate
      resemblance. A control experiment indicated these effects were caused neither by
      lower resemblance of other-sex faces than same-sex faces, nor by an increased
      perception of averageness or familiarity of same-sex faces due to prototyping or
      mere exposure affecting only same-sex faces. The differential impact of self
      resemblance on our perception of same-sex and other-sex faces supports the
      hypothesis that humans use facial resemblance as a cue of kinship.

PMID- 15451702
TI  - Memoir and performance: social change and self life-writing among men who are gay
      pornography producers and actors.
AB  - Identity may be understood both as a life-story, either told or written as memoir
      or autobiography, and also as a practice such as producing or acting in gay
      pornographic film, but always within the context of social and historical change.
      Study of the memoirs of gay men who have been actors and/or producers of gay
      pornographic films across three generation cohorts provides an opportunity for
      understanding the interplay of social change and life circumstances in making gay
      identity. This perspective on identity is illustrated through the study of the
      memoirs of three men from different cohorts who have produced and acted in gay
      pornographic films: Wakefield Poole, born in 1936; Scott O'Hara, born in 1961;
      and Aaron Lawrence, born in 1971. Differences in style and content of both memoir
      and practice in gay pornographic films reflect changing social expectations
      regarding men who have sex with men following the emergence of the gay rights
      movement and the AIDS epidemic.

PMID- 15451703
TI  - Body image, eating disorders, and the drive for muscularity in gay and
      heterosexual men: the influence of media images.
AB  - This Internet research project examined the relationship between consumption of
      muscle and fitness magazines and/or various indices of pornography and body
      satisfaction in gay and heterosexual men. Participants (N = 101) were asked to
      complete body satisfaction questionnaires that addressed maladaptive eating
      attitudes, the drive for muscularity, and social physique anxiety. Participants
      also completed scales measuring self-esteem, depression, and socially desirable
      responding. Finally, respondents were asked about their consumption of muscle and
      fitness magazines and pornography. Results indicated that viewing and purchasing
      of muscle and fitness magazines correlated positively with levels of body
      dissatisfaction for both gay and heterosexual men. Pornography exposure was
      positively correlated with social physique anxiety for gay men. The limitations
      of this study and directions for future research are outlined.

PMID- 15451704
TI  - If you look at it long enough...
AB  - "If you look at it long enough..." is a user's account--40 years of looking at
      pornography. It attempts to raise issues around gay studies and academic
      "detachment." It is, to a great extent, autobiographical. But it also is the
      voice of a character speaking. A persona. It is a tribute to pornography and
      pornographers.

PMID- 15451705
TI  - Homecoming: the relevance of radical feminism for gay men.
AB  - Sexual politics in the gay male world would be enhanced by a serious engagement
      with radical feminist politics, particularly critiques of pornography and the sex
      industry. As the domination/subordination dynamic at the heart of patriarchy
      damages homosexual men, such engagement is crucial to the future of a gay
      movement.

PMID- 15451706
TI  - Educating gay male youth: since when is pornography a path towards self-respect?
AB  - In 2000, in the case of Little Sisters Book and Art Emporium, the Canadian
      Supreme Court was asked to determine whether gay male pornography violated the
      sex equality protections guaranteed by the Canadian Charter of Rights and
      Freedoms. Throughout this case, gay male activists and academics emphasised the
      risk posed by antipornography legal strategies to the dissemination of materials
      intended to promote safer sexual behaviour. Other arguments were advanced that
      gay male pornography should not be restricted because it serves as a learning
      tool for young men and, in so doing, does much to reduce the alarming incidence
      of gay youth suicide. The author examines these assumptions within the context of
      the gay male pornography defended in Little Sisters. His conclusion is that the
      present gay male obsession with hyper-masculinity, best evidenced in the
      pornography now widely touted by some gay men as a source of gay male identity
      and freedom, undermines safer sexual practices and the self-respect needed to
      combat youth suicide. The author concludes that gay men must commit to a
      sexuality built on mutuality, respect and caring (i.e., an identity politic built
      around sex equality).

PMID- 15451707
TI  - The queer sensitive interveners in the Little Sisters case: a response to Dr.
      Kendall.
AB  - Three queer sensitive organizations intervened before the Supreme Court of Canada
      in Little Sisters v. Canada, a case that challenged whether and how Canada
      Customs treated cross border shipments to a gay and lesbian bookstore. This paper
      reviews the queer sensitive organizations' arguments on some of the issues in the
      case, especially the scope of obscenity law, and challenges misconceptions about
      their positions, including those presented in Dr. Kendall's paper (appearing in
      this volume).

PMID- 15451708
TI  - In the slammer: the myth of the prison in American gay pornographic video.
AB  - The purpose of this paper is to discuss the significance of the prison scenario
      and its various permutations in the texts of American commercial pornographic
      video. The paper will identify the prison as a highly eroticised all male
      environment, an arena where the active/passive dichotomy of gay pornography is
      staged and re-staged. The significances of the prison are multiple. The prison
      draws on a gay mythology of homosexual desire that has its origins in sources as
      diverse as the literature of the Marquis de Sade and Jean Genet and the erotic
      illustrations of Tom of Finland and Etienne. Prison scenarios take many shapes in
      gay pornography such as the American penitentiary, the military brig, and the
      fantasised dungeon of the leatherman. I see these scenarios as performing an
      important function within gay porn by offering idealised spaces for the acts of
      pornography: voyeurism, narcissistic display and active/ passive role-play.

PMID- 15451709
TI  - "He was treating me like trash, and I was loving it...": perspectives in gay male
      pornography.
AB  - As the topic of gay male pornography has received limited attention from social
      scientists, little is known about how gay men perceive this medium. In the
      current study, a focus group methodology was used whereby participants examined
      specific scenes from commercially available gay pornography in terms of the
      messages they disseminate about the body and gay sexuality, in general. Findings
      suggest that discussants tended to view the medium from a utilitarian
      perspective. They saw pornography as a masturbatory aid, and did not believe that
      it possessed much significance vis-a-vis gay men's attitudes and behaviours.
      Those who identified potentially negative influences of this medium saw them as
      transitory and most likely to occur among gay men other than themselves.

PMID- 15451710
TI  - Sex pigs: why porn is like sausage, or the truth is that--behind the scenes--porn
      is not very sexy.
AB  - The author examines the gay adult video industry from an insider's perspective.
      The workaday reality of making porn is contrasted with the skin trade's glamorous
      myths, and the idea that porn consumers prefer these myths to "truth" is
      outlined.

PMID- 15451711
TI  - Alterity and construction of national identity in three Kristen Bjorn films.
AB  - In the gay pornographic films Manly Beach (1991), Call of the Wild (1992) and
      Paradise Plantation (1994), director Kristen Bjorn capitalises on the appeal of
      alterity, or "otherness." By using exotic locations and national stereotypes, he
      provides North American viewers with idealised sexual scenarios that are
      different, but not too different, from that with which they are familiar.

PMID- 15451712
TI  - Porn again: some final conclusions.
AB  - Contributors were asked to respond to seven questions examining various aspects
      of gay male pornography. Their responses were collated with the hope that the
      reader may gain additional insight into this topic.

PMID- 15451713
TI  - Interdiscplinary team processes within an in-home service delivery organization.
AB  - Interdisciplinary teamwork is particularly difficult to achieve in the community
      context where geographical separateness and solo practices impede face to face
      contact and collaborative practice. Understanding the processes that occur within
      interdisciplinary teams is imperative, since client outcomes are influenced by
      interdisciplinary teamwork. The purpose of this exploratory study was to describe
      the processes that occur within interdisciplinary teams that deliver in-home
      care. Applying grounded theory methodology, the researcher conducted unstructured
      in-depth interviews with a purposeful sample of healthcare providers and used
      constant comparative analysis to elicit the findings. Findings revealed three key
      team processes: networking, navigating, and aligning. The descriptions afford
      several insights that are applicable to in-home healthcare agencies attempting to
      achieve effective interdisciplinary team functioning.

PMID- 15451714
TI  - Sources of systematic error in instruments measuring satisfaction with home care.
AB  - The concept of systematic error (SE) is used in this review as a framework for
      appraising the only two studies reporting psychometric testing of instruments of
      home-care satisfaction (HCS). The development of each tool is summarized. General
      sources of SE are discussed relative to instrumentation, the process of
      measurement, and participants. Sources of SE that researchers in HCS have tried
      to remedy in each category are covered. The typical approaches to those problems
      are critically analyzed relative to the validity of the construct of HCS. Ideas
      are proposed to enhance the empirical grounding of the construct through (a)
      eliciting and analyzing data about expectations as well as data about
      satisfaction and (b) counteracting the interaction among response set, direct
      referent items, and skewness in studies of HCS.

PMID- 15451715
TI  - Use of home care services by elderly Chinese immigrants.
AB  - Using the Anderson Service model, this study examined the level and predictors of
      using selected home care services by elderly Chinese immigrants in Canada. Data
      from 1,537 randomly selected Chinese immigrants aged 65 years and older were
      used. Only 5.2% of participants reported using home care services. Being older,
      living alone, having a post-secondary education, immigrating from Hong Kong or
      Southeast Asia, having a higher level of agreement with Chinese health beliefs,
      higher social support, and poorer physical and mental health were predictors for
      home care service use among elderly Chinese. The probability of using homecare
      services lessens with increased self-rated financial adequacy. These findings
      point to the need for service providers to address the gap in use of home care
      between elderly Chinese immigrants and overall elderly Canadians through
      promoting appropriate use of home care among elderly Chinese immigrants.

PMID- 15451716
TI  - The role of intended use on actual use of home care: is race a factor?
AB  - Previous studies indicate that African American elders are less likely to use
      institutional long-term care than whites. The purpose of this study was to
      examine whether an individual's intention to use home care may mediate the effect
      of race on the actual use of home care. This study was a prospective,
      longitudinal study of 208 Connecticut residents over age 65. Findings indicated
      that African American elders' use of home care is associated with their intention
      to use services, while white elders' use of home care is associated with need.
      This suggests that the factors that predict long-term care use differ for African
      American and white elders. Therefore, the traditional models of health services
      use may need to be expanded in order to explain patterns of use among nonwhite
      populations.

PMID- 15451717
TI  - Home health outcome patterns.
AB  - Using OASIS data collected by all Medicare-certified home health agencies, this
      article first presents descriptive statistics on patient outcomes for a national
      agency sample in 2001, soon after Medicare prospective payment implementation.
      Ratios of actual to predicted outcome rates, aggregated for groups of outcomes,
      are considered as potential summary indicators of agency outcome performance. The
      aggregate ratios show promise, but information on each outcome remains critical
      to agencies' outcome improvement efforts. Ratios for some outcomes are
      interrelated, suggesting that agencies focusing outcome enhancement efforts on a
      few target outcomes also may improve related outcomes.

PMID- 15451718
TI  - Abstracts of the 6th National Congress of Medical Oncology. September 21-24,
      2004. Bologna, Italy.

PMID- 15451721
TI  - Pseudopollen in Eria Lindl. section Mycaranthes Rchb.f. (Orchidaceae).
AB  - BACKGROUND AND AIMS: Pseudopollen is a whitish, mealy material produced upon the
      labella of a number of orchid species as labellar hairs either become detached or
      fragment. Since individual hair cells are rich in protein and starch, it has long
      been speculated that pseudopollen functions as a reward for visiting insects.
      Although some 90 years have passed since Beck first described pseudopollen for a
      small number of Eria spp. currently assigned to section Mycaranthes Rchb.f., we
      still know little about the character of pseudopollen in this taxon. The use of
      SEM and histochemistry would re-address this deficit in our knowledge whereas
      comparison of pseudopollen in Eria (S.E. Asia), Maxillaria (tropical and sub
      tropical America), Polystachya (largely tropical Africa and Madagascar) and
      Dendrobium unicum (Thailand and Laos) would perhaps help us to understand better
      how this feature may have arisen and evolved on a number of different continents.
      METHODS: Pseudopollen morphology is described using light microscopy and scanning
      electron microscopy. Hairs were tested for starch, lipid and protein using IKI,
      Sudan III and the xanthoproteic test, respectively. KEY RESULTS AND CONCLUSIONS:
      The labellar hairs of all eight representatives of section Mycaranthes examined
      are identical. They are unicellular, clavate with a narrow 'stalk' and contain
      both protein and starch but no detectable lipid droplets. The protein is
      distributed throughout the cytoplasm and the starch is confined to amyloplasts.
      The hairs become detached from the labellar surface and bear raised cuticular
      ridges and flaky deposits that are presumed to be wax. In that they are
      unicellular and appear to bear wax distally, the labellar hairs are significantly
      different from those observed for other orchid species. Comparative morphology
      indicates that they evolved independently in response to pollinator pressures
      similar to those experienced by other unrelated pseudopollen-forming orchids on
      other continents.

PMID- 15451722
TI  - Floral development of Berberidopsis corallina: a crucial link in the evolution of
      flowers in the core Eudicots.
AB  - BACKGROUND AND AIMS: On the basis of molecular evidence Berberidopsidaceae have
      been linked with Aextoxicaceae in an order Berberidopsidales at the base of the
      core Eudicots. The floral development of Berberidopsis is central to the
      understanding of the evolution of floral configurations at the transition of the
      basal Eudicots to the core Eudicots. It lies at the transition of trimerous or
      dimerous, simplified apetalous forms into pentamerous, petaliferous flowers.
      METHODS: The floral ontogeny of Berberidopsis was studied with a scanning
      electron microscope. KEY RESULTS: Flowers are grouped in terminal racemes with
      variable development. The relationship between the number of tepals, stamens and
      carpels is more or less fixed and floral initiation follows a strict 2/5
      phyllotaxis. Two bracteoles, 12 tepals, eight stamens and three carpels are
      initiated in a regular sequence. The number of stamens can be increased by a
      doubling of stamen positions. CONCLUSIONS: The floral ontogeny of Berberidopsis
      provides support for the shift in floral bauplan from the basal Eudicots to the
      core Eudicots as a transition of a spiral flower with a 2/5 phyllotaxis to
      pentamerous flowers with two perianth whorls, two stamen whorls and a single
      carpel whorl. The differentiation of sepals and petals from bracteotepals is
      discussed and a comparison is made with other Eudicots with a similar
      configuration and development. Depending on the resolution of the relationships
      among the basalmost core Eudicots it is suggested that Berberidopsis either
      represents a critical stage in the evolution of pentamerous flowers of major
      clades of Eudicots, or has a floral prototype that may be at the base of
      evolution of flowers of other core Eudicots. The distribution of a floral Bauplan
      in other clades of Eudicots similar to Berberidopsidales is discussed.

PMID- 15451723
TI  - The importance of injury prevention.

PMID- 15451724
TI  - John Henryism--the same old song?

PMID- 15451725
TI  - Health in rural America: remembering the importance of place.

PMID- 15451726
TI  - Aiming at "de feet" and diabetes: a rural model to increase annual foot
      examinations.
AB  - Something is afoot in south central Idaho. After 2 years of work, the percentage
      of people with diabetes receiving recommended annual foot examinations has
      increased by 13.8%, exceeding the state average. This turnaround, from being the
      region with the lowest percentage of foot examinations in the state, was made
      possible when South Central District Health joined diabetes coalition members to
      develop a comprehensive program that maximizes limited resources in the rural, 8
      county service area. Key program components include (1) development of a
      curriculum on CD-ROM called 2 Minute Diabetes Foot Examination, (2) training area
      physicians and nurses in the curriculum, (3) incorporating the curriculum into
      the nursing program at the local college, (4) offering free foot-screening
      clinics to targeted populations, and (5) conducting public education and
      outreach.

PMID- 15451727
TI  - The pitfalls of bioterrorism preparedness: the anthrax and smallpox experiences.
AB  - Bioterrorism preparedness programs have contributed to death, illness, and waste
      of public health resources without evidence of benefit. Several deaths and many
      serious illnesses have resulted from the smallpox vaccination program; yet there
      is no clear evidence that a threat of smallpox exposure ever existed. The anthrax
      spores released in 2001 have been linked to secret US military laboratories-the
      resultant illnesses and deaths might not have occurred if those laboratories were
      not in operation. The present expansion of bioterrorism preparedness programs
      will continue to squander health resources, increase the dangers of accidental or
      purposeful release of dangerous pathogens, and further undermine efforts to
      enforce international treaties to ban biological and chemical weapons. The public
      health community should acknowledge the substantial harm that bioterrorism
      preparedness has already caused and develop mechanisms to increase our public
      health resources and to allocate them to address the world's real health needs.

PMID- 15451728
TI  - Implementing the Institute of Medicine's recommended curriculum content in
      schools of public health: a baseline assessment.
AB  - In September 2003, the Association of Schools of Public Health administered an
      online survey to representatives of all 33 accredited US schools of public
      health. The survey assessed the extent to which the schools were offering
      curriculum content in the 8 areas recommended by the Institute of Medicine:
      communication, community-based participatory research, cultural competence,
      ethics, genomics, global health, informatics, and law/policy. Findings indicated
      that, for the most part, schools of public health are offering content in these
      areas through many approaches and have incorporated various aspects of a broad
      based ecological approach to public health education and training. The findings
      also suggested the possible need for greater content in genomics, informatics,
      community-based participatory research, and cultural competence.

PMID- 15451729
TI  - Rural health disparities, population health, and rural culture.
AB  - In this commentary, I place the maturing field of rural health research and
      policy in the context of the rural health disparities documented in Health United
      States, 2001, Urban and Rural Health Chartbook. Because of recent advances in our
      understanding of the determinants of health, the field must branch out from its
      traditional focus on access to health care services toward initiatives that are
      based on models of population health. In addition to presenting distinct regional
      differences, the chartbook shows a pattern of risky health behaviors among rural
      populations that suggest a "rural culture" health determinant. This pattern
      suggests that there may be environmental and cultural factors unique to towns,
      regions, or United States Department of Agriculture (USDA) economic types that
      affect health behavior and health.

PMID- 15451730
TI  - Rural public health service delivery: promising new directions.
AB  - I describe variations in the structure and in the practice of rural public health
      and how rural communities meet the challenges of current public health practice,
      including primary methods of service delivery and partnership development. I
      present examples of promising models for the creation of rural public health
      capacity-the ability of local health departments to carry out core public health
      responsibilities.

PMID- 15451731
TI  - The importance of place of residence: examining health in rural and nonrural
      areas.
AB  - We examined differences in health measures among rural, suburban, and urban
      residents and factors that contribute to these differences. Whereas differences
      between rural and urban residents were observed for some health measures, a
      consistent rural-to-urban gradient was not always found. Often, the most rural
      and the most urban areas were found to be disadvantaged compared with suburban
      areas. If health disparities are to be successfully addressed, the relationship
      between place of residence and health must be understood.

PMID- 15451732
TI  - Provision of health care in rural Afghanistan: needs and challenges.
AB  - Afghanistan's health system is severely limited in terms of preventive and
      curative services, referral systems, and human resources. Most of the country's
      citizens reside in rural areas, a majority of which are served by "basic health
      units" (small and simple facilities that provide primary care), and these rural
      residents face additional challenges regarding timely access to quality health
      care. The analysis described in this article, which focuses on data derived from
      2 rural health units during a 1-year period, revealed that infectious diseases,
      mainly acute respiratory infections, were a primary concern and that there is a
      clear need for increasing access to health services. In addition, our results
      showed that women are underrepresented as patients and appear to be at higher
      risk than men of tuberculosis.

PMID- 15451733
TI  - Acute traumatic injuries in rural populations.
AB  - In the United States, injuries are the leading cause of death among individuals
      aged 1 to 45 years and the fourth leading cause of death overall. Rural
      populations exhibit disproportionately high injury mortality rates. Deaths
      resulting from motor vehicle crashes, traumatic occupational injuries, drowning,
      residential fires, and suicide all increase with increasing rurality. We describe
      differences in rates and patterns of injury among rural and urban populations and
      discuss factors that contribute to these differences.

PMID- 15451734
TI  - Depression-era malaria control in the South.

PMID- 15451735
TI  - Person and place: the compounding effects of race/ethnicity and rurality on
      health.
AB  - Rural racial/ethnic minorities constitute a forgotten population. The limited
      research addressing rural Black, Hispanic, and American Indian/Alaska Native
      populations suggests that disparities in health and in health care access found
      among rural racial/ethnic minority populations are generally more severe than
      those among urban racial/ethnic minorities. We suggest that disparities must be
      understood as both collective and contextual phenomena. Rural racial/ethnic
      minority disparities in part stem from the aggregation of disadvantaged
      individuals in rural areas. Disparities also emerge from a context of limited
      educational and economic opportunity. Linking public health planning to the
      education and economic development sectors will reduce racial/ethnic minority
      disparities while increasing overall well-being in rural communities.

PMID- 15451736
TI  - Addressing externalities from swine production to reduce public health and
      environmental impacts.
AB  - Animal agriculture in the United States for the most part has industrialized,
      with negative consequences for air and water quality and antibiotic use. We
      consider health and environmental impacts of current US swine production and give
      an overview of current federal, state, and local strategies being used to address
      them.

PMID- 15451737
TI  - Providing health care to Latino immigrants: community-based efforts in the rural
      midwest.
AB  - We examined case studies of 3 rural Midwestern communities to assess local health
      care systems' response to rapidly growing Latino populations. Currently, clinics
      provide free or low-cost care, and schools, public health, social services, and
      religious organizations connect Latinos to the health care system. However, many
      unmet health care needs result from lack of health insurance, limited income, and
      linguistic and cultural barriers. Targeted safety net funding would help meet
      Latino health care needs in rural communities with limited resources.

PMID- 15451738
TI  - Rural healthy people 2010--evolving interactive practice.
AB  - The objectives of the Rural Healthy People 2010 project are to employ a survey of
      state and local rural health leaders to identify rural health priorities, to
      synthesize available research and other publications on these priorities, to
      identify and describe models for practice employed by rural communities to
      address these priorities, and to disseminate this information to rural
      communities. We describe these priorities; the content of Rural Healthy People
      2010 products, methods, and target audiences; and the continuing evolution of the
      program. Rural Healthy People 2010 encourages rural support of Healthy People
      2010 goals and invites state and local rural health leaders to share their
      successful models with others.

PMID- 15451739
TI  - Education-related gender differences in health in rural China.
AB  - We investigated gender differences in education-related health inequalities in
      rural China. Household interview data were obtained from 6 provinces in 1993 and
      2001. Remarkable health inequalities existed and favored the higher educational
      groups; among women, the inequalities were greater and health inequalities
      increased from 1993 to 2001. Education serves as a more powerful mediating factor
      for health inequalities among women than among men in rural China.

PMID- 15451740
TI  - Rurality and nursing home quality: results from a national sample of nursing home
      admissions.
AB  - OBJECTIVES: We examined differences in quality of care among nursing homes in
      locales of varying degrees of rurality. METHODS: We classified locales into 4
      classes according to rurality. We analyzed a 10% sample of nursing home
      admissions in the United States in 2000 (n=198613) to estimate survival models
      for 9 quality indicators. RESULTS: For postacute admissions, we observed
      significant differences in rates of decline for residents in facilities in large
      towns compared with urban areas, but differences in quality were both negative
      and positive. Among admissions for long-term or chronic care, rates of decline in
      2 of 9 quality areas were lower for residents in isolated areas. CONCLUSIONS: We
      observed significant differences in a number of quality indicators among
      different classes of nursing home locations, but differences varied dramatically
      according to type of admission. These differences did not exhibit the
      monotonicity that we would have expected had they derived solely from rurality.
      Also, quality indicators exhibited more similarities than differences across the
      4 classes of locales. The results underscore the importance, in some instances,
      of emphasizing the effects of specific settings rather than some continuum of
      rurality and of moving beyond the assumption that nursing home residents
      constitute a homogeneous population.

PMID- 15451741
TI  - Retention of primary care physicians in rural health professional shortage areas.
AB  - OBJECTIVES: We tested the assumption that average job retention duration is
      shorter for physicians in rural health professional shortage areas (HPSAs) than
      for physicians in rural non-HPSAs. METHODS: In 1991, we surveyed nationally
      representative samples of primary care physicians who recently had moved to rural
      HPSAs and non-HPSAs who were without service obligations. We resurveyed these
      physicians in 1996 and 1997 to learn of any job changes. RESULTS: Physicians in
      rural HPSAs (n=308) demonstrated retention similar to that of the non-HPSA cohort
      (n=197) (hazard ratio for leaving=1.28; 95% confidence interval=0.97, 1.69;
      P=.08), even with adjustments for group demographic differences (P=.24).
      CONCLUSIONS: Average retention duration for generalist physicians in rural HPSAs
      is identical to or slightly shorter than for those in rural non-HPSAs. Poor
      recruitment is likely to be the principal dynamic underlying local rural
      shortages.

PMID- 15451742
TI  - Results from a lay health advisor intervention to prevent lead poisoning among
      rural Native American children.
AB  - OBJECTIVES: We tested the effectiveness of a community-based lay health advisor
      intervention for primary prevention of lead poisoning among Native American
      children who lived in a former mining area. METHODS: We conducted cross-sectional
      population-based blood lead assessments of Native American and White children
      aged 1 to 6 years and in-person caregiver interviews before (n=331) and after
      (n=387) a 2-year intervention. RESULTS: Mean childhood blood lead levels
      decreased and selected preventive behaviors improved for both Native American and
      White (comparison) communities. Several short-term outcomes also improved from
      pre- to postintervention, but only knowledge and hand-washing self-efficacy
      increased more among Native Americans than among Whites. CONCLUSIONS: Our
      findings provide limited support for the effectiveness of lay health advisor
      interventions as a primary lead poisoning prevention strategy for Native American
      communities.

PMID- 15451743
TI  - Pounds off with empowerment (POWER): a clinical trial of weight management
      strategies for black and white adults with diabetes who live in medically
      underserved rural communities.
AB  - OBJECTIVES: We evaluated lifestyle interventions for diabetic persons who live in
      rural communities. METHODS: We conducted a 12-month randomized clinical trial (n
      = 152) of "intensive-lifestyle" (modeled after the NIH Diabetes Prevention
      Program) and "reimbursable-lifestyle" (intensive-lifestyle intervention delivered
      in the time allotted for Medicare reimbursement for diabetes education related to
      nutrition and physical activity) interventions with usual care as a control.
      RESULTS: Modest weight loss occurred by 6 months among intensive-lifestyle
      participants and was greater than the weight loss among usual-care participants
      (2.6 kg vs 0.4 kg, P<.01). At 12 months, a greater proportion of intensive
      lifestyle participants had lost 2 kg or more than usual-care participants (49% vs
      25%, P<.05). No differences in weight change were observed between reimbursable
      lifestyle and usual-care participants. Glycated hemoglobin was reduced among all
      groups (P<.05) but was not different between groups. CONCLUSIONS: Improvement in
      both weight and glycemia was attainable by lifestyle interventions designed for
      persons who had type 2 diabetes and lived in rural communities.

PMID- 15451744
TI  - Impact of a national rural youth health and safety initiative: results from a
      randomized controlled trial.
AB  - OBJECTIVES: We conducted a comprehensive evaluation of a rural youth health and
      safety initiative implemented in 4000 National FFA (formerly Future Farmers of
      America) chapters across the United States. METHODS: Data were collected from
      high school students and their FFA advisers at 3 time intervals (preintervention,
      immediate postintervention, and 1 year postintervention) with a 3-group
      (standard, enhanced, and control), cluster-randomized, controlled trial design.
      RESULTS: Matched data from 3081 students and 81 advisers revealed no significant
      effect of this initiative on agricultural health and safety knowledge, safety
      attitudes, leadership, self-concept, and self-reported injuries of project
      participants. Data from 30 public health nurses following the intervention
      confirmed the program's failure to develop sustainable community partnerships.
      CONCLUSIONS: This nationally coordinated initiative was funded with more than $1
      million donated by agribusinesses. Program implementation was inconsistent, and
      desired outcomes were not achieved. Future efforts should better guide effective
      use of private sector resources aimed at reducing agricultural disease and injury
      among rural youths.

PMID- 15451745
TI  - Urban-rural shifts in intentional firearm death: different causes, same results.
AB  - OBJECTIVES: We analyzed urban-rural differences in intentional firearm death.
      METHODS: We analyzed 584629 deaths from 1989 to 1999 assigned to 3141 US
      counties, using negative binomial regressions and an 11-category urban-rural
      variable. RESULTS: The most urban counties had 1.03 (95% confidence interval
      [CI]=0.87, 1.20) times the adjusted firearm death rate of the most rural
      counties. The most rural counties experienced 1.54 (95% CI=1.29, 1.83) times the
      adjusted firearm suicide rate of the most urban. The most urban counties
      experienced 1.90 (95% CI=1.50, 2.40) times the adjusted firearm homicide rate of
      the most rural. Similar opposing trends were not found for nonfirearm suicide or
      homicide. CONCLUSIONS: Firearm suicide in rural counties is as important a public
      health problem as firearm homicide in urban counties. Policymakers should become
      aware that intentional firearm deaths affect all types of communities in the
      United States.

PMID- 15451746
TI  - Fatal occupational injury rates in southern and non-southern States, by race and
      Hispanic ethnicity.
AB  - OBJECTIVES: We investigated fatal occupational injury rates in the United States
      by race and Hispanic ethnicity during the period 1990-1996. METHODS: Fatalities
      were identified by means of the national traumatic occupational fatalities
      surveillance system. Fatal occupational injury rates were calculated by
      race/ethnicity and region using US-census-based workforce estimates. RESULTS: Non
      Hispanic Black men in the South had the highest fatal occupational injury rate
      (8.5 per 100000 worker-years), followed by Hispanic men in the South (7.9 per
      100000 worker-years). Fatal injury rates for Hispanic men increased over the
      study period, exceeding rates for non-Hispanic Black men in the latter years of
      observation. CONCLUSIONS: These data suggest a change in the demographics of
      fatal occupational injuries in the United States. Hispanic men in the South
      appear to be emerging as the group with the nation's highest unintentional fatal
      occupational injury rate.

PMID- 15451747
TI  - Differences in health-related quality of life in rural and urban veterans.
AB  - OBJECTIVES: We sought to determine whether disparities in health-related quality
      of life exist between veterans who live in rural settings and their suburban or
      urban counterparts. METHODS: We determined health-related quality-of-life scores
      (physical and mental health component summaries) for 767109 veterans who had used
      Veterans Health Administration services within the past 3 years. We used
      rural/urban commuting area codes to categorize veterans into rural, suburban, or
      urban residence. RESULTS: Health-related quality-of-life scores were
      significantly lower for veterans who lived in rural settings than for those who
      lived in suburban or urban settings. Rural veterans had significantly more
      physical health comorbidities, but fewer mental health comorbidities, than their
      suburban and urban counterparts. Rural-urban disparities persisted in all survey
      subscales, across regional delivery networks, and after we controlled for
      sociodemographic factors. CONCLUSIONS: When compared with their urban and
      suburban counterparts, veterans who live in a rural setting have worse health
      related quality-of-life scores. Policymakers, within and outside the Veterans
      Health Administration, should anticipate greater health care demands from rural
      populations.

PMID- 15451748
TI  - Local area deprivation and urban-rural differences in anxiety and depression
      among people older than 75 years in Britain.
AB  - OBJECTIVES: We sought to determine the association of depression and anxiety with
      "area deprivation" (neighborhood socioeconomic deprivation) and population
      density among people older than 75 years in Britain. METHODS: Postal codes were
      used to link census area information to individual data on depression and anxiety
      in 13349 people aged 75 years and older taking part in a trial of health
      screening. RESULTS: Living in the most socioeconomically deprived areas was
      associated with depression (OR=1.4), but this relation disappeared after
      adjusting for individual deprivation characteristics. There was no association
      with anxiety. Living in the highest density and intermediate low-density areas
      was associated with depression (OR=1.6 and 1.5) and anxiety (OR=1.5 and 1.3)
      compared with the lowest density areas. CONCLUSIONS: An association between area
      deprivation and depression in older people was explained by individual health,
      demographic, and socioeconomic factors. Higher population density was
      consistently associated with increased depression and anxiety.

PMID- 15451749
TI  - Underuse of screening sigmoidoscopy and colonoscopy in a large cohort of US
      adults.
AB  - OBJECTIVES: We examined the prevalence of endoscopy (sigmoidoscopy or
      colonoscopy) by indication and by demographic and lifestyle factors. METHODS: We
      analyzed cross-sectional data collected in 1997 from participants aged 50 years
      and older in the Cancer Prevention Study (CPS) II Nutrition Cohort. RESULTS:
      Fifty-eight percent of men and 51% of women reported ever having undergone
      endoscopy; only 42% of men and 31% of women reported endoscopy for screening
      rather than for disease diagnosis or follow-up. Prevalence varied by demographic
      and lifestyle factors. CONCLUSIONS: Efforts to increase colorectal cancer
      screening need to target women, all persons aged 50-64 years, and those with
      colorectal cancer risk factors. Future studies should distinguish endoscopy for
      screening from procedures for disease diagnosis and follow-up to avoid
      overestimating screening compliance.

PMID- 15451750
TI  - Cost-related medication underuse among chronically ill adults: the treatments
      people forgo, how often, and who is at risk.
AB  - OBJECTIVES: We sought information about the cost-related underuse of medications
      which medications are underused, by whom, and how often. METHODS: Chronically ill
      adults were asked to identify how often they underused prescription medication
      for 16 health conditions because of the cost. RESULTS: Eighteen percent of
      respondents cut back on medication use owing to cost in the previous year, and
      14% used less medication at least monthly. Although rates of underuse varied
      substantially across treatments, prescription coverage and out-of-pocket costs
      were determinants of underuse across medication types. CONCLUSIONS: Many
      chronically ill adults frequently cut back on medications owing to cost. Patients
      are selective about the treatments they forgo. Out-of-pocket costs and inadequate
      prescription coverage may lead to adherence problems for many important
      medication types.

PMID- 15451751
TI  - Barriers to health care access among the elderly and who perceives them.
AB  - OBJECTIVES: We evaluated self-perceived access to health care in a cohort of
      Medicare beneficiaries. METHODS: We identified patterns of use and barriers to
      health care from self-administered questionnaires collected during the 1993-1994
      annual examination of the Cardiovascular Health Study. RESULTS: The
      questionnaires were completed by 4889 (91.1%) participants, with a mean age of
      76.0 years. The most common barriers to seeing a physician were the doctor's lack
      of responsiveness to patient concerns, medical bills, transportation, and street
      safety. Low income, no supplemental insurance, older age, and female gender were
      independently related to perceptions of barriers. Race was not significant after
      adjustment for other factors. CONCLUSIONS: Psychological and physical barriers
      affect access to care among the elderly; these may be influenced by poverty more
      than by race.

PMID- 15451752
TI  - Changes in racial differences in use of medical procedures and diagnostic tests
      among elderly persons: 1986-1997.
AB  - OBJECTIVES: We used 1997 Medicare data to replicate an earlier study that used
      data from 1986 to examine racial differences in usage of specific medical
      procedures or tests among elderly persons. METHODS: We used 1997 physician claims
      data to obtain a random sample of 5% of Medicare beneficiaries aged 65 years and
      older. We used this sample to study 30 procedures and tests that were analyzed in
      the 1986 study, as well as several new procedures that became more widely used in
      the early 1990s. RESULTS: Racial differences remain in the rates of use of these
      procedures; in general, Blacks have lower rates of use than do Whites. Between
      1986 and 1997, the ratio of White to Black use moved in favor of Blacks for all
      but 4 of the established procedures studied. CONCLUSIONS: The White-Black gap in
      health care use under Medicare is narrowing.

PMID- 15451753
TI  - Predictors of beginning and ending caregiving during a 3-year period in a
      biracial community population of older adults.
AB  - OBJECTIVES: We sought to identify predictors of beginning and ending caregiving.
      METHODS: At baseline and 3-year follow-up, we interviewed 4245 community
      residents (61.4% Black, 38.4% White, 0.20% other) aged 65 years or older. We used
      logistic regression to test predictors of beginning caregiving among baseline
      noncaregivers and of continuing caregiving among baseline caregivers. RESULTS:
      After control for demographic variables, physically healthier individuals were
      significantly more likely to become caregivers and to continue caregiving. Mental
      health had little influence on beginning caregiving, but declining mental heath
      was associated with continuing caregiving. CONCLUSIONS: Maintenance of physical
      health and function is essential to the ability of older adults to begin and to
      continue caregiving. Studies that compare the health of current caregivers with
      that of noncaregivers may substantially underestimate the impact of caregiving on
      health.

PMID- 15451755
TI  - Prostate cancer screening: a racial dichotomy.

PMID- 15451754
TI  - Neighborhood context and mortality among older Mexican Americans: is there a
      barrio advantage?
AB  - OBJECTIVES: We examined whether Mexican Americans living in high-density Mexican
      American neighborhoods experience increased morbidity and mortality compared with
      the rates observed among Mexican Americans living in low-density areas. METHODS:
      We conducted a prospective analysis of a cohort of 3050 Mexican Americans aged 65
      years or older. We examined prevalence of 6 medical conditions and survival over
      7 years of follow-up in relation to percentage of Mexican Americans in the census
      tract. RESULTS: With adjustment for covariates, odds for disease prevalence among
      older Mexican Americans as a function of percentage of Mexican Americans in the
      census tract were 0.33 (95% confidence interval [CI]=0.16, 0.71) for stroke, 0.28
      (95% CI= 0.11, 0.70) for cancer, and 0.31 (95% CI=0.10, 0.98) for hip fracture.
      The hazard ratio for all-cause mortality over 7 years' follow-up was 0.64 (95%
      CI=0.42, 0.96). CONCLUSIONS: Sociocultural advantages conferred on Mexican
      Americans by living in high-density Mexican American neighborhoods outweigh the
      disadvantages conferred by the high poverty of those neighborhoods.

PMID- 15451756
TI  - Food for afterthought: reflections from 2 implantable cardioverter defibrillator
      trials.

PMID- 15451757
TI  - Physicians' interactions with third-party payers: is deception necessary?
AB  - Published reports indicate that physicians sometimes use deceptive tactics with
      third-party payers. Many physicians appear to be willing to deceive to secure
      care that they perceive as necessary, particularly when illnesses are severe and
      appeals procedures for care denials are burdensome. Physicians whose practices
      include larger numbers of Medicaid or managed care patients seem more willing to
      deceive third-party payers than are other physicians. The use of deception has
      important implications for physician professionalism, patient trust, and rational
      health policy development. If deception is as widespread as these studies
      suggest, there may be serious problems in the medical profession and the health
      care financing systems at the interface between physicians and third-party
      payers. Deception may be a symptom of a flawed system, in which physicians are
      asked to implement financing policies that conflict with their primary obligation
      to the patient.

PMID- 15451758
TI  - Smokeless tobacco and cardiovascular risk.
AB  - This article discusses the evolution of smokeless tobacco in the United States
      and interprets the available data on cardiovascular risk factors and
      cardiovascular mortality associated with its use. There has been a resurgence of
      smokeless tobacco use since 1970. Smokeless tobacco consistently produces levels
      of nicotine higher than those seen with smoking and causes similar sympathetic
      neural stimulation and acute cardiovascular effects. However, there is
      conflicting evidence from prospective and case-control studies about
      cardiovascular mortality or myocardial infarction caused by smokeless tobacco
      use. Smokeless tobacco use is also associated with oral cancers and high-risk
      behavior in adolescents. Although the evidence is not conclusive, the adverse
      cardiovascular effects of smokeless tobacco use are less than those caused by
      smoking but are more than those found in nonusers. It is advisable to counsel all
      current users of smokeless tobacco to quit. Behavioral counseling, sustained
      release bupropion hydrochloride therapy, and nicotine replacement therapy may be
      safe therapeutic modalities for treatment of smokeless tobacco use.

PMID- 15451759
TI  - Treatment of hypertension in patients with diabetes.
AB  - At least 17 million people in the United States have diabetes mellitus, and
      another 50 million have hypertension. These chronic diseases increasingly coexist
      in our aging population. Both diseases are important predisposing factors for the
      development of cardiovascular disease (CVD) and renal disease, and the
      coexistence of these risk factors is a very powerful promoter of CVD and renal
      disease. There is accumulating evidence that the rigorous treatment of
      hypertension and other risk factors such as dyslipidemia and hyperglycemia
      considerably lessens the burden of CVD and renal disease in patients with
      diabetes mellitus. There is considerable evidence that strategies addressing diet
      and exercise reduce the development of diabetes and are an important component of
      treatment in persons who have established diabetes. There are also considerable
      data suggesting that the treatment strategies that interrupt the renin
      angiotensin system have special benefits in patients with diabetes and may
      prevent the development of clinical diabetes in hypertensive patients with
      impaired glucose tolerance. Data from a recent study indicate that the control of
      systolic blood pressure, using a diuretic agent as part of antihypertensive
      therapy, reduces the risk of stroke and other CVD end points. Recent reports
      indicate that angiotensin receptor-blocking agents decrease the rate of
      development of proteinuria and diabetic renal disease. These observations will
      likely have a significant impact on treatment of hypertension in patients with
      type 2 diabetes mellitus.

PMID- 15451760
TI  - Racial differences in screening for prostate cancer in the elderly.
AB  - BACKGROUND: Black men are more likely than white men to be diagnosed as having
      advanced prostate cancer, and their prostate cancer mortality rates are more than
      twice as high. Low screening rates among black men may contribute to these
      disparities, but there are few data on racial differences in prostate cancer
      screening. OBJECTIVES: To present a case-control study of racial differences in
      the use of prostate-specific antigen (PSA) as a screening test among Medicare
      beneficiaries in New Jersey and to assess the degree to which race is associated
      with prostate cancer screening. METHODS: The study used a statewide database of
      claims data from Medicare Parts A and B, Medicaid, and the state's Pharmaceutical
      Assistance for the Aged and Disabled program. Prevalent cases of prostate cancer
      were excluded using the state's cancer registry. Of 139 672 men who underwent PSA
      screening, 34 984 were randomly selected along with an identical number of
      controls matched by month and year of birth. After men with International
      Classification of Diseases, Ninth Revision, Clinical Modification,or Current
      Procedural Terminology codes indicative of prostate cancer were excluded, 33 463
      case patients and 33 782 control subjects remained. RESULTS: The use of PSA
      screening was strongly and inversely associated with black race (odds ratio [OR]
      = 0.50; P<.001), poverty (OR = 0.33; P<.001), and near poverty (OR = 0.69;
      P<.001). Multivariate logistic regression analysis after age, socioeconomic
      status, comorbidity, and use of health care services were controlled for revealed
      that black race remained a strong predictor of not undergoing PSA screening (OR =
      0.65; 95% confidence interval, 0.60-0.70). CONCLUSIONS: Elderly blacks are
      substantially less likely to undergo PSA screening than elderly whites.
      Differences in socioeconomic status and comorbid conditions explain only a small
      part of the racial differences in screening rates.

PMID- 15451761
TI  - Effects of hospitalist attending physicians on trainee satisfaction with teaching
      and with internal medicine rotations.
AB  - BACKGROUND: Hospitalists are increasingly serving as inpatient attendings at
      teaching hospitals. The educational impact of this new model is unclear. We
      evaluated the relationship between type of attending (hospitalist vs traditional)
      and trainees' ratings of attending teaching and the overall ward rotation.
      METHODS: We analyzed data from a Web-based evaluation system containing all house
      staff and student evaluations of their attendings and internal medicine ward
      rotations at 2 university-affiliated teaching hospitals over a 2-year period
      (1999-2001). RESULTS: The overall evaluation completion rate was 91% (1587 of
      1742 evaluations) by trainees working with 17 hospitalists and 52 traditional
      attendings. Trainees reported significantly more overall satisfaction with
      hospitalists than traditional attendings (8.3 vs 8.0 on a 9-point scale; P<.001)
      and rated hospitalists' overall teaching effectiveness as superior (4.8 vs 4.5 on
      a 5-point scale; P<.001). Perceived overall educational value of rotations was
      higher with hospitalist attendings (3.9 vs 3.7 on a 5-point scale; P =.04).
      Trainees evaluated hospitalists' knowledge, teaching, and feedback as superior to
      that of traditional attendings. There were no significant differences in reports
      of attendings' interest in teaching or patients, availability, or emphasis on
      cost-effectiveness. CONCLUSIONS: Trainees reported more effective teaching and
      more satisfying inpatient rotations when supervised by hospitalists. This
      analysis suggests that hospitalists may possess or accrue a specific inpatient
      knowledge base and teaching skill that distinguishes them from nonhospitalists.

PMID- 15451762
TI  - Prospective study of social and other risk factors for incidence of type 2
      diabetes in the Whitehall II study.
AB  - BACKGROUND: Social inequalities in the incidence of type 2 diabetes and the
      relation of health behaviors and psychosocial factors to the incidence of type 2
      diabetes are not well established. METHODS: Prospective occupational cohort study
      of 10 308 civil servants aged 35 to 55 years at baseline in phase 1 (1985-1988).
      Diagnosis of diabetes was ascertained by questionnaire at baseline and follow-up
      at phases 2 (1989), 3 (1992-1993), 4 (1995), and 5 (1997-1999) and glucose
      tolerance tests in phases 3 and 5. RESULTS: Participants working in the lower
      employment grades had a higher incidence of diabetes than those in higher
      employment grades (men: odds ratio [OR], 2.9; 95% confidence interval [CI], 1.9
      4.4; women: OR, 1.7 [95% CI, 0.8-3.7]). Body mass index and other risk factors
      considered traditional for type 2 diabetes were found to be so in this cohort. In
      men, of the psychosocial risk factors examined, only effort-reward imbalance was
      related to incidence of diabetes (OR, 1.7 [95% CI, 1.0-2.8]). The General Health
      Questionnaire depression subscale was related to incidence of diabetes and
      impaired glucose tolerance (OR, 1.25 [95% CI, 1.0-1.6]). These associations
      remained after adjustment for other confounding factors. In men only, social
      difference in incidence of diabetes was reduced but still significant after
      adjustment for conventional risk factors. CONCLUSIONS: An inverse relationship
      exists between social position and incidence of diabetes that is partly explained
      by health behaviors and other risk factors. Effort-reward imbalance, which is
      reportedly associated with coronary heart disease, is also associated with type 2
      diabetes.

PMID- 15451763
TI  - Colon cancer screening practices following genetic testing for hereditary
      nonpolyposis colon cancer (HNPCC) mutations.
AB  - BACKGROUND: Although increased colonoscopic surveillance is recommended for
      hereditary nonpolyposis colon cancer (HNPCC) mutation carriers, limited
      information is available on adherence to colorectal cancer screening
      recommendations. This study investigated colonoscopy practices following genetic
      testing for HNPCC mutations. METHODS: This prospective cohort study was conducted
      between May 22, 1996, and November 13, 1999. Participants were 98 men and women
      without a personal history of colon cancer or colectomy who were identified from
      11 extended HNPCC families. Colonoscopy use was evaluated by telephone before
      genetic counseling and was reassessed 1, 6, and 12 months following test results
      disclosure. RESULTS: During the 12 months following genetic counseling and
      testing, 73% (16/22) of HNPCC mutation carriers, 16% (8/49) of noncarriers, and
      22% (6/27) of decliners reported having a colonoscopy (chi(2) = 23.97, P<.001).
      After controlling for clinical factors and pretest screening practices, HNPCC
      mutation carriers were significantly more likely than test decliners to have a
      colonoscopy (odds ratio [OR], 12.12; 95% confidence interval [CI], 3.42-42.96;
      P<.001). There were no differences in colonoscopy use between noncarriers and
      decliners (OR, 0.60; 95% CI, 0.28-1.29; P =.19). Perceived control over
      developing colon cancer also had a significant effect on posttest colonoscopy use
      (OR, 2.19; 95% CI, 1.22-3.94; P =.01). CONCLUSIONS: Genetic testing may motivate
      increased colonoscopic screening among HNPCC mutation carriers. Increased efforts
      may be needed to assess patients' family histories of colon cancer and provide
      appropriate referrals for genetic counseling and testing to target colonoscopic
      screening to high-risk individuals.

PMID- 15451764
TI  - Cognitive behavior therapy and pharmacotherapy for insomnia: a randomized
      controlled trial and direct comparison.
AB  - BACKGROUND: Chronic sleep-onset insomnia is a prevalent health complaint in
      adults. Although behavioral and pharmacological therapies have been shown to be
      effective for insomnia, no placebo-controlled trials have evaluated their
      separate and combined effects for sleep-onset insomnia. The objective of this
      study was to evaluate the clinical efficacy of behavioral and pharmacological
      therapy, singly and in combination, for chronic sleep-onset insomnia. METHODS:
      This was a randomized, placebo-controlled clinical trial that involved 63 young
      and middle-aged adults with chronic sleep-onset insomnia. Interventions included
      cognitive behavior therapy (CBT), pharmacotherapy, or combination therapy
      compared with placebo. The main outcome measures were sleep-onset latency as
      measured by sleep diaries; secondary measures included sleep diary measures of
      sleep efficiency and total sleep time, objective measures of sleep variables
      (Nightcap sleep monitor recorder), and measures of daytime functioning. RESULTS:
      In most measures, CBT was the most sleep effective intervention; it produced the
      greatest changes in sleep-onset latency and sleep efficiency, yielded the largest
      number of normal sleepers after treatment, and maintained therapeutic gains at
      long-term follow-up. The combined treatment provided no advantage over CBT alone,
      whereas pharmacotherapy produced only moderate improvements during drug
      administration and returned measures toward baseline after drug use
      discontinuation. CONCLUSIONS: These findings suggest that young and middle-age
      patients with sleep-onset insomnia can derive significantly greater benefit from
      CBT than pharmacotherapy and that CBT should be considered a first-line
      intervention for chronic insomnia. Increased recognition of the efficacy of CBT
      and more widespread recommendations for its use could improve the quality of life
      of a large numbers of patients with insomnia.

PMID- 15451765
TI  - Breast cancer risk in primary care: implications for chemoprevention.
AB  - BACKGROUND: Some women may benefit from taking tamoxifen citrate for breast
      cancer prevention if the probability of benefit outweighs that of adverse events.
      We determined the proportion of women aged 40 to 69 years attending general
      internal medicine practices who were potentially eligible for tamoxifen
      chemoprevention and calculated the maximum proportion of breast cancers that
      could be prevented. METHODS: Six hundred five women aged 40 to 69 completed self
      administered questionnaires in the waiting rooms of 10 general internal medicine
      practices in North Carolina in 2001. RESULTS: Among white women, 9.0% (95%
      confidence interval [CI], 5.1%-15.2%) in their 40s, 24.0% (95% CI, 18.2%-31.0%)
      in their 50s, and 53.4% (95% CI, 46.1%-61.3%) in their 60s had a 5-year Gail
      model estimated breast cancer risk of 1.66% or greater. Among black women, 2.9%
      (95% CI, 0%-15.0%) in their 40s, 7.1% (95% CI, 1.1%-24.4%) in their 50s, and
      13.0% (95% CI, 3.1%-34.3%) in their 60s had a similar risk. When adverse events
      were considered in white women, 10% or fewer in all age groups were potentially
      eligible for chemoprevention. The maximum proportion of breast cancers prevented
      in eligible women was 6.0% to 8.3%. CONCLUSIONS: Small numbers of women in
      primary care practices are eligible for discussions about chemoprevention; the
      maximum proportion of breast cancers prevented if eligible women take tamoxifen
      is also small. Challenges lie in targeting discussions to the most appropriate
      women and in finding new chemoprevention strategies that have less risk of harms.

PMID- 15451766
TI  - Effect of Helicobacter pylori eradication on platelet recovery in patients with
      chronic idiopathic thrombocytopenic purpura.
AB  - BACKGROUND: A relationship between Helicobacter pylori infection and idiopathic
      thrombocytopenic purpura (ITP) has previously been reported. We determined the
      prevalence of H pylori infection in Japanese patients with chronic ITP and the
      effect of its eradication on platelet count. METHODS: The study population
      comprised 53 Japanese adults with chronic ITP and a platelet count of less than
      100 x 10(3)/ micro L. A (13)C-urea breath test was performed to determine H
      pylori infection status. Those patients who were H pylori positive gave written
      informed consent and received eradication therapy. The effect of H pylori
      eradication on platelet count was evaluated up to 6 months after therapy.
      Clinical parameters were compared between responders to the therapy (increase in
      platelet count) and nonresponders, as well as between H pylori-positive and 
      negative patients. RESULTS: Of the 53 patients with chronic ITP in the study, 39
      (74%) were H pylori positive. Of the 32 infected patients who received treatment,
      H pylori was successfully eradicated in 27 patients (84%). In 10 (37%) of these
      patients, this resulted in a favorable platelet response. A partial response was
      seen in 5 additional patients (19%). A significant (P<.001) increase in platelet
      count was demonstrated in patients in whom H pylori was successfully eradicated
      but not in patients who were unsuccessfully treated or in untreated patients.
      Current corticosteroid therapy was reported more often in nonresponders than in
      responders. CONCLUSION: Eradication of H pylori may prove effective in increasing
      platelet count in H pylori-positive patients with chronic ITP.

PMID- 15451767
TI  - Postservice mortality in Vietnam veterans: 30-year follow-up.
AB  - BACKGROUND: During the 1980s, the postservice mortality component of the Vietnam
      Experience Study was conducted to examine the health effects of the Vietnam
      experience. This study was limited by the relatively short follow-up and the
      young age of the veterans. Thus, a follow-up mortality investigation on this
      cohort was undertaken to further assess the impact of the Vietnam experience on
      chronic conditions. METHODS: Vital status and underlying cause-of-death data on
      the Vietnam Experience Study cohort (18 313 male US Army veterans) were
      retrospectively ascertained from the end of the original study through 2000. Cox
      proportional hazards regression was used to calculate crude and adjusted rate
      ratios (RRs) for all-cause and cause-specific mortality, comparing Vietnam and
      non-Vietnam veterans. RESULTS: All-cause mortality was 7% higher in Vietnam vs
      non-Vietnam veterans during 30-year follow-up (95% confidence interval [CI], 0.97
      1.18). The excess mortality among Vietnam veterans was isolated to the first 5
      years after discharge from active duty and resulted from an increase in external
      causes of death (RR, 1.62; 95% CI, 1.16-2.26). Cause-specific analyses revealed
      no difference in disease-related mortality. Vietnam veterans, however,
      experienced excess unintentional poisoning (RR, 2.26; 95% CI, 1.12-4.57) and drug
      related (RR, 1.70; 95% CI, 1.01-2.86) deaths throughout follow-up. CONCLUSIONS:
      Vietnam veterans continued to experience higher mortality than non-Vietnam
      veterans from unintentional poisonings and drug-related causes. Death rates from
      disease-related chronic conditions, including cancers and circulatory system
      diseases, did not differ between Vietnam veterans and their peers, despite the
      increasing age of the cohort (mean age, 53 years) and the longer follow-up
      (average, 30 years).

PMID- 15451768
TI  - Cardiovascular disease, mortality, and retinal microvascular characteristics in
      type 1 diabetes: Wisconsin epidemiologic study of diabetic retinopathy.
AB  - BACKGROUND: Diabetic retinopathy and proteinuria, manifestations of microvascular
      abnormalities, occur early in the course of diabetes mellitus; in contrast,
      macrovascular cardiovascular complications usually occur later. Retinal vessel
      characteristics may be informative about risk of cardiovascular disease in
      persons with diabetes. We evaluated this in a longitudinal cohort study of
      persons with type 1 diabetes. METHODS: The population consisted of persons with
      type 1 diabetes who were receiving care in 11 counties in Wisconsin. Subjects (n
      = 996) were examined at baseline (1980-1982), and 4, 10, 14, and 20 years later.
      Evaluations included medical history and measurements of height, weight, blood
      pressure, and glycosylated hemoglobin. Fundus photographs were graded for
      diabetic retinopathy at baseline, and the same photographs were graded later for
      the diameters of retinal blood vessels. At each examination, a history of
      cardiovascular disease events since the last examination (and prior to baseline)
      was obtained. Mortality was monitored yearly. RESULTS: The 20-year age-adjusted
      cumulative incidences were 18.1% for angina, 14.8% for myocardial infarction, and
      5.9% for stroke. Severity of diabetic retinopathy was associated with angina and
      stroke. Arteriovenous ratio was associated with myocardial infarction. Of 273
      deaths, 176 involved heart disease. The severity of retinopathy and arteriovenous
      ratio was associated with heart disease mortality. Nephropathy was more
      informative about the cardiovascular end points than were the blood vessel
      characteristics. CONCLUSIONS: Incidences of cardiovascular disease, including
      mortality, were common in people with type 1 diabetes during a 20-year interval.
      Retinal vascular characteristics were associated with these end points, but this
      association was confounded by nephropathy.

PMID- 15451769
TI  - Diabetic ketoacidosis in type 1 and type 2 diabetes mellitus: clinical and
      biochemical differences.
AB  - BACKGROUND: Diabetic ketoacidosis (DKA), once thought to typify type 1 diabetes
      mellitus, has been reported to affect individuals with type 2 diabetes mellitus.
      An analysis and overview of the different clinical and biochemical
      characteristics of DKA that might be predicted between patients with type 1 and
      type 2 diabetes is needed. METHODS: We reviewed 176 admissions of patients with
      moderate-to-severe DKA. Patients were classified as having type 1 or type 2
      diabetes based on treatment history and/or autoantibody status. Groups were
      compared for differences in symptoms, precipitants, vital statistics, biochemical
      profiles at presentation, and response to therapy. RESULTS: Of 138 patients
      admitted for moderate-to-severe DKA, 30 had type 2 diabetes. A greater proportion
      of the type 2 diabetes group was Latino American or African American (P<.001).
      Thirty-five admissions (19.9%) were for newly diagnosed diabetes. A total of 85%
      of all admissions involved discontinuation of medication use, 69.2% in the type 2
      group. Infections were present in 21.6% of the type 1 and 48.4% of the type 2
      diabetes admissions. A total of 21% of patients with type 1 diabetes and 70% with
      type 2 diabetes had a body mass index greater than 27. Although the type 1
      diabetes group was more acidotic (arterial pH, 7.21 +/- 0.12 vs 7.27 +/- 0.08;
      P<.001), type 2 diabetes patients required longer treatment periods (36.0 +/-
      11.6 vs 28.9 +/- 8.9 hours, P =.01) to achieve ketone-free urine. Complications
      from therapy were uncommon. CONCLUSIONS: A significant proportion of DKA occurs
      in patients with type 2 diabetes. The time-tested therapy for DKA of intravenous
      insulin with concomitant glucose as the plasma level decreases, sufficient fluid
      and electrolyte replacement, and attention to associated problems remains the
      standard of care, irrespective of the type of diabetes.

PMID- 15451770
TI  - Prothrombin 20210A mutation: a mild risk factor for venous thromboembolism but
      not for arterial thrombotic disease and pregnancy-related complications in a
      family study.
AB  - BACKGROUND: The prothrombin 20210A mutation has been associated with an increased
      risk of venous thromboembolism (VTE). Its relationship with arterial disease and
      pregnancy-related complications is, however, still uncertain. The aim of this
      study was to estimate the incidences of first venous and arterial thrombotic
      events and pregnancy-related complications in relatives of patients with the
      mutation. METHODS: After clinical classification, the presence of the mutation
      was determined in first-degree relatives of consecutive patients with the
      mutation and a history of VTE or premature atherosclerosis. Relatives with and
      without the mutation were compared. RESULTS: Of all relatives, 204 (50%) were
      heterozygous, 5 were homozygous, and 198 had a normal genotype. The annual
      incidence of a first episode of VTE was 0.35% and 0.18% in carriers and
      noncarriers, respectively (odds ratio [OR], 1.9; 95% confidence interval [CI],
      0.9-4.1); the annual incidence of a first arterial thrombosis was 0.22% and 0.15%
      in carriers and noncarriers, respectively (OR, 2.3; 95% CI, 0.8-6.3). The annual
      incidence of a first myocardial infarction was 0.14% (95% CI, 0.05%-0.23%) and
      0.05% (0.01%-0.14%) in carriers and noncarriers, respectively (OR, 4.7; 95% CI,
      1.0-22.5; P =.06). In particular, homozygous carriers were at increased risk of
      VTE (OR, 6.0; 95% CI, 1.3-27.2), whereas a history of VTE in the proband
      influenced the risk of VTE in the relatives. Women with the mutation did not
      experience significantly more pregnancy-related complications than their
      relatives with a normal genotype. CONCLUSIONS: The prothrombin mutation is a mild
      risk factor for VTE within families of carriers but does not seem to play an
      important role in arterial thrombotic disease, with the exception of myocardial
      infarction, or in pregnancy-related complications.

PMID- 15451771
TI  - Proteinase-activated receptor-4: evaluation of tethered ligand-derived peptides
      as probes for receptor function and as inflammatory agonists in vivo.
AB  - 1. We evaluated the ability of a number of peptides based on the tethered ligand
      sequences of human, rat and murine proteinase-activated receptor-4 (PAR(4)), to
      serve as receptor-activating probes or antagonists for bioassays carried out in
      vitro and for in vivo models of inflammation. 2. In a rat PAR(4)-dependent
      platelet aggregation assay, the relative potencies of the active sequences
      (AYPGKF-NH(2)>GYPGKF-NH(2)>GYPGFK-NH(2)>GFPGKP-NH(2)) were consistent with an
      activation of PAR(4). 3. In the aggregation assay, the reverse or partial reverse
      sequence peptides (VQGPYG-NH(2), YAPGKF-NH(2) and FKGPYA-NH(2)) were inactive,
      while trans-cinnamoyl (Tc)-YPGKF-NH(2), Tc-APGKF-NH(2) and N-palmitoyl-SGRRYGHALR
      NH(2) (pepducin P4pal-10) were antagonists. 4. However, in an endothelium
      dependent NO-mediated rat aorta (RA) relaxation assay and in a gastric
      longitudinal muscle (LM) contraction assay, these antagonist peptides were
      agonists as were most other peptides, with distinct orders of potencies that
      differed for both the RA and LM assays and from the platelet assay. 5. We
      conclude that PAR(4)-derived tethered ligand peptide agonists can act at
      receptors other than PAR(4) and that a judicious choice of ligands is required to
      probe for PAR(4) function in bioassay systems and in particular for in vivo
      models. 6. By selecting from these peptides the ones most reliably reflecting
      PAR(4) activation (AYPGKF-NH(2) as a standard agonist; YAPGKF-NH(2) as a PAR(4)
      inactive standard), we were able to establish an inflammatory role for the PAR(4)
      activating peptides acting via a non-neurogenic mechanism in a rat paw oedema
      model.

PMID- 15451772
TI  - G protein activation and cyclic AMP modulation by naloxone benzoylhydrazone in
      distinct layers of rat olfactory bulb.
AB  - 1 Naloxone benzoylhydrazone (NalBzoH) has initially been developed as an agonist
      of the pharmacologically defined kappa3-opioid receptor and has recently been
      employed as an antagonist at the opioid receptor-like (ORL1) receptor. In the
      present study, we investigated the ability of NalBzoH to elicit agonist-like
      effects on receptor signalling in distinct layers of rat olfactory bulb, a brain
      region where we have demonstrated the presence of opioid and ORL1 receptors
      coupled to both stimulation and inhibition of cyclic AMP formation. 2 In
      membranes of the olfactory nerve-glomerular layer (ON-GL), external plexiform
      layer (EPL) and granule cell layer (GRL), NalBzoH elicited a concentration
      dependent stimulation of guanosine-5'-O-(3-[35S]-thio)triphosphate
      ([35S]GTPgammaS) binding with pEC50 values ranging from 7.36 to 7.86, whereas the
      kappa1-opioid receptor agonists (-)-U-50,488 and U-69,593 were inactive. 3 In
      membranes of GRL, but not ON-GL and EPL, NalBzoH stimulated basal adenylyl
      cyclase activity by 40% with a pEC50 of 8.14, and significantly potentiated the
      net enzyme stimulation elicited by corticotropin-releasing hormone and pituitary
      adenylate cyclase-activating peptide 38. Pertussis toxin prevented the NalBzoH
      stimulations of [35S]GTPgammaS binding and adenylyl cyclase activity. 4 In
      membranes of EPL and GRL, but not ON-GL, NalBzoH elicited a concentration
      dependent inhibition of forskolin-stimulated adenylyl cyclase activity with pEC50
      values of 8.07 and 8.08, respectively. 5 At concentrations that completely
      blocked the actions of nociceptin/orphanin FQ (N/OFQ), the ORL1 receptor
      antagonists CompB and [Nphe1]N/OFQ(1-13)NH2 failed to antagonize either the
      stimulatory or the inhibitory effect of NalBzoH on cyclic AMP formation.
      Similarly, the kappa1-opioid receptor antagonist nor-binaltorphimine counteracted
      the NalBzoH effects with relatively low potencies (pKi values=7.67-8.09). 6
      Conversely, the selective delta-opioid receptor antagonist TIPP (pKi=9.10) and
      the selective mu-opioid receptor antagonist CTAP (pKi=8.27) reduced the
      inhibitory effect of NalBzoH by 70 and 30%, respectively. Moreover, TIPP and CTAP
      potently inhibited the NalBzoH stimulation of cyclic AMP, each antagonist
      maximally causing 50% blockade of the agonist response. 7These data demonstrate
      that in the olfactory bulb NalBzoH activates receptor signalling by acting
      through delta- and mu-opioid receptors and independently of ORL1 and kappa1
      opioid receptors.

PMID- 15451773
TI  - Comparison of the antinociceptive activity of two new NO-releasing derivatives of
      the NSAID S-ketoprofen in rats.
AB  - 1 Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase (COX)
      enzymes inducing analgesic, anti-inflammatory and antipyretic actions. They are
      not devoid of severe side effects and so, the search for new compounds with
      similar or higher effectiveness and a lower incidence of undesired actions is
      important. Nitric oxide (NO)-releasing NSAIDs resulted from this search. 2 We
      have compared the antinociceptive effectiveness of cumulative doses of two new NO
      releasing derivatives of S-ketoprofen, HCT-2037 and HCT-2040, using the recording
      of spinal cord nociceptive reflexes in anesthetized and awake rats and after
      intravenous and oral administration. 3 S-ketoprofen and HCT-2040 were
      equieffective in reducing responses to noxious mechanical stimulation after i.v.
      administration in anesthetized animals (ID50s: 1.3+/-0.1 and 1.6+/-0.2 micromol
      kg(-1) respectively), but did not modify wind-up. HCT-2037 was two-fold more
      potent (ID50 of 0.75+/-0.1 micromol kg(-1)) in responses to mechanical stimuli
      and very effective in reducing wind-up (63+/-17% of control; P<0.01; MED: 0.4
      micromol kg(-1)), indicating a greater activity than the parent compound. 4 In
      awake animals with inflammation, HCT-2037 p.o. fully inhibited mechanical
      allodynia, 91+/-12% reduction, and hyperalgesia, 94+/-8% reduction. Equivalent
      doses of S-ketoprofen only partially reduced either allodynia (50+/-11%) or
      hyperalgesia (40+/-4%). The effect on responses to noxious thermal stimulation
      was similar for the two compounds. 5 We conclude that the molecular changes made
      in the structure of S-ketoprofen including an NO moiety in its structure, improve
      the antinociceptive profile of the compound opening new perspectives in a safer
      use of NSAIDs as analgesic drugs.

PMID- 15451775
TI  - Allosteric modulation of semicarbazide-sensitive amine oxidase activities in
      vitro by imidazoline receptor ligands.
AB  - 1. Evidence indicates that imidazoline I(2) binding sites (I(2)BSs) are present
      on monoamine oxidase (MAO) and on soluble (plasma) semicarbazide-sensitive amine
      oxidase enzymes. The binding site on MAO has been described as a modulatory site,
      although no effects on activity are thought to have been observed as a result of
      ligands binding to these sites. 2. We examined the effects in vitro of several
      imidazoline binding site ligands on activities of bovine plasma amine oxidase
      (BPAO) and porcine kidney diamine oxidase (PKDAO) in a spectrophotometric
      protocol. 3. While both enzymes were inhibited at high concentrations of all
      ligands, clonidine, cirazoline and oxymetazoline were seen, at lower
      concentrations, to increase activity of BPAO versus benzylamine, but not of PKDAO
      versus putrescine. This effect was substrate dependent, with mixed or biphasic
      inhibition of spermidine, methylamine, p-tyramine and beta-phenylethylamine
      oxidation observed at cirazoline concentrations that increased benzylamine
      oxidation. 4. With benzylamine as substrate, clonidine decreased K(M) (EC(50)
      8.82 microm, E(max) 75.1% of control) and increased V(max) (EC(50) 164.6 microm,
      E(max) 154.1% of control). Cirazoline decreased V(max) (EC(50) 2.15 microm,
      E(max) 91.4% of control), then decreased K(M) (EC(50) 5.63 microm, E(max) 42.6%
      of control) and increased V(max) (EC(50) 49.0 microm, E(max) 114.4% of decreased
      V(max) value). 5. Data for clonidine fitted a mathematical model for two-site
      nonessential activation plus linear intersecting noncompetitive inhibition. Data
      for cirazoline were consistent with involvement of a fourth site. 6. These
      results reveal an ability of imidazoline ligands to modulate BPAO kinetics
      allosterically. The derived mechanism may have functional significance with
      respect to modulation of MAO by I(2)BS ligands.

PMID- 15451776
TI  - Sympathectomy reveals alpha 1A- and alpha 1D-adrenoceptor components to
      contractions to noradrenaline in rat vas deferens.
AB  - We have previously demonstrated that contractions of rat vas deferens to
      exogenous noradrenaline involve predominantly alpha(1A)-adrenoceptors, but that
      contractions to endogenous noradrenaline involve predominantly alpha(1D)
      adrenoceptors. In this study, we have examined the effects of sympathectomy on
      the subtypes of alpha(1)-adrenoceptor in rat vas deferens in radioligand binding
      and functional studies. In vehicle-treated tissues, antagonist displacement of
      [(3)H]prazosin binding to alpha(1)-adrenoceptors was consistent with a single
      population of alpha(1)-adrenoceptors. Binding affinities for a range of alpha(1)
      adrenoceptor antagonists were expressed as pK(i) values and correlated with known
      affinities for alpha(1)-adrenoceptor subtypes. The correlation was significant
      only with alpha(1A)-adrenoceptors. In tissues from rats sympathectomised with 6
      hydroxy-dopamine (2 x 100 mg kg(-1) i.p.), binding affinity for the alpha(1D)
      adrenoceptor antagonist BMY 7378 fitted best with a two-site model. In functional
      studies, the potency of noradrenaline at producing total (phasic plus tonic) but
      not tonic contractions was increased in tissues from sympathectomised rats.
      Results obtained from sympathectomised rats suggest that phasic contractions are
      mainly alpha(1D)-adrenoceptor mediated, whereas tonic contractions are mainly
      alpha(1A)-adrenoceptor mediated, based on the effects of BMY 7378 and the
      alpha(1A)-adrenoceptor antagonist RS 100329. It is concluded that the predominant
      alpha(1)-adrenoceptor in vehicle-treated rat vas deferens is the alpha(1A)
      adrenoceptor, both in terms of ligand binding and contractions to exogenous
      agonists. The alpha(1D)-adrenoceptor is only detectable by ligand binding
      following chemical sympathectomy, but is involved in noradrenaline-evoked
      contractions, particularly phasic contractions, of rat vas deferens.

PMID- 15451777
TI  - Maternal calcium intake and offspring blood pressure.
AB  - BACKGROUND: Few data exist on the intergenerational influence of calcium intake
      during pregnancy on offspring blood pressure. METHODS AND RESULTS: As part of the
      ongoing US prospective cohort study Project Viva, we analyzed 4091 Dinamap blood
      pressure measurements from 936 six-month-old infants whose mothers had completed
      food frequency questionnaires during the second trimester of pregnancy. We used
      mixed models to estimate effects of maternal calcium intake on offspring systolic
      blood pressure. Mean+/-SD daily total maternal calcium intake was 1494+/-523 mg,
      consisting of 1230+/-486 mg from foods and 264+/-191 mg from supplements. Mean+/
      SD 6-month blood pressure was 89.9+/-12.9 mm Hg. From bottom to top quartile of
      dietary calcium from foods adjusted for energy intake and measurement conditions,
      mean infant systolic blood pressures were 91.0, 90.2, 90.9, and 90.2 mm Hg (trend
      P=0.62). From calcium supplements only, the values were 91.5, 90.2, 90.4, and
      88.4 mm Hg (trend P=0.006). After further adjustment for demographic,
      anthropometric, dietary, social, and economic variables, the decrease in 6-month
      systolic blood pressure was -3.0 mm Hg (95% CI, -4.9 to -1.1) for each 500-mg
      increment of maternal supplemental calcium intake during pregnancy. We did not
      find evidence of effect modification by maternal vitamin D or potassium intake or
      by infant body mass index. First-trimester calcium intake was not associated with
      offspring blood pressure. CONCLUSIONS: These observational data suggest that
      supplementing maternal midgestational calcium intake may lower offspring blood
      pressure, thus helping to prevent hypertension in the next generation.

PMID- 15451778
TI  - Usefulness of exercise testing in the prediction of coronary disease risk among
      asymptomatic persons as a function of the Framingham risk score.
AB  - BACKGROUND: The purpose of this study is to determine the usefulness of exercise
      treadmill testing (ETT) among asymptomatic persons in predicting coronary heart
      disease (CHD) events over and above the Framingham CHD risk score. METHODS AND
      RESULTS: Subjects included 3043 members of the Framingham Heart Study offspring
      cohort without CHD (1431 men and 1612 women; age, 45+/-9 years) who underwent ETT
      and were followed up for 18.2 years. The risk of developing CHD was evaluated
      relative to 3 exercise test variables: (1) ST-segment depression > or =1 mm, (2)
      failure to achieve target heart rate (THR) of 85% predicted maximum, and (3)
      exercise capacity. In multivariable analyses that adjusted for age and Framingham
      CHD risk score, among men, ST-segment depression (hazard ratio [HR], 1.88; 95%
      CI, 1.21 to 2.91) and failure to achieve THR (HR, 1.70; 95% CI, 1.18 to 2.45)
      predicted higher CHD risk, whereas a greater exercise capacity predicted lower
      CHD risk (HR per MET, 0.94; 95% CI, 0.89 to 0.99). Although similar HRs were seen
      in women, those results were not statistically significant. Among men with 10
      year predicted risk > or =20%, failure to reach THR and ST-segment depression
      both more than doubled the risk of an event (HR, 2.66 and HR, 2.11,
      respectively), and each MET increment in exercise capacity reduced risk by 13%
      (HR, 0.87). CONCLUSIONS: Among asymptomatic men, ST-segment depression, failure
      to reach THR, and exercise capacity during ETT provided additional prognostic
      information in age- and Framingham risk score-adjusted models, particularly among
      those in the highest risk group (10-year predicted CHD risk of > or =20%). The
      evaluation of exercise test variables in women is limited, given our sample size
      and the few CHD events in women.

PMID- 15451780
TI  - Plaque neovascularization is increased in ruptured atherosclerotic lesions of
      human aorta: implications for plaque vulnerability.
AB  - BACKGROUND: Growth of atherosclerotic plaques is accompanied by
      neovascularization from vasa vasorum microvessels extending through the tunica
      media into the base of the plaque and by lumen-derived microvessels through the
      fibrous cap. Microvessels are associated with plaque hemorrhage and may play a
      role in plaque rupture. Accordingly, we tested this hypothesis by investigating
      whether microvessels in the tunica media, the base of the plaque, and the fibrous
      cap are increased in ruptured atherosclerotic plaques in human aorta. METHODS AND
      RESULTS: Microvessels, defined as CD34-positive tubuloluminal capillaries
      recognized in cross-sectional and longitudinal profiles, were quantified in 269
      advanced human plaques by bicolor immunohistochemistry. Macrophages/T lymphocytes
      and smooth muscle cells were defined as CD68/CD3-positive and alpha-actin
      positive cells. Total microvessel density was increased in ruptured plaques when
      compared with nonruptured plaques (P=0.0001). Furthermore, microvessel density
      was increased in lesions with severe macrophage infiltration at the fibrous cap
      (P=0.0001) and at the shoulders of the plaque (P=0.0001). In addition,
      microvessel density was also increased in lesions with intraplaque hemorrhage
      (P=0.04) and in thin-cap fibroatheromas (P=0.038). Logistic regression analysis
      identified plaque base microvessel density (P=0.003) as an independent correlate
      to plaque rupture. CONCLUSIONS: Thus, neovascularization as manifested by the
      localized appearance of microvessels is increased in ruptured plaques in the
      human aorta. Furthermore, microvessel density is increased in lesions with
      inflammation, with intraplaque hemorrhage, and in thin-cap fibroatheromas.
      Microvessels at the base of the plaque are independently correlated with plaque
      rupture, suggesting a contributory role for neovascularization in the process of
      plaque rupture.

PMID- 15451779
TI  - Endocannabinoids acting at cannabinoid-1 receptors regulate cardiovascular
      function in hypertension.
AB  - BACKGROUND: Endocannabinoids are novel lipid mediators with hypotensive and
      cardiodepressor activity. Here, we examined the possible role of the
      endocannabinergic system in cardiovascular regulation in hypertension. METHODS
      AND RESULTS: In spontaneously hypertensive rats (SHR), cannabinoid-1 receptor
      (CB1) antagonists increase blood pressure and left ventricular contractile
      performance. Conversely, preventing the degradation of the endocannabinoid
      anandamide by an inhibitor of fatty acid amidohydrolase reduces blood pressure,
      cardiac contractility, and vascular resistance to levels in normotensive rats,
      and these effects are prevented by CB1 antagonists. Similar changes are observed
      in 2 additional models of hypertension, whereas in normotensive control rats, the
      same parameters remain unaffected by any of these treatments. CB1 agonists lower
      blood pressure much more in SHR than in normotensive Wistar-Kyoto rats, and the
      expression of CB1 is increased in heart and aortic endothelium of SHR compared
      with Wistar-Kyoto rats. CONCLUSIONS: We conclude that endocannabinoids tonically
      suppress cardiac contractility in hypertension and that enhancing the CB1
      mediated cardiodepressor and vasodilator effects of endogenous anandamide by
      blocking its hydrolysis can normalize blood pressure. Targeting the
      endocannabinoid system offers novel therapeutic strategies in the treatment of
      hypertension.

PMID- 15451781
TI  - Selective inhibition of cyclooxygenase-2 enhances platelet adhesion in hamster
      arterioles in vivo.
AB  - BACKGROUND: Selective inhibitors of cyclooxygenase-2 (Cox-2) are reported to
      cause cardiovascular side effects in patients at risk. However, direct proof of
      prothrombotic effects of these drugs is lacking. We investigated in the
      microcirculation in vivo whether selective inhibition of Cox-2 induces platelet
      activation. METHODS AND RESULTS: The behavior of fluorescence-labeled human
      platelets was studied in hamster arterioles (dorsal skinfold chamber) by
      intravital microscopy. Transient platelet-vessel wall interactions (PVWIs), firm
      platelet adhesion to the vessel wall, and vessel occlusion after FeCl3-induced
      wall injury were analyzed as platelet activation parameters. In vitro experiments
      in human umbilical vein endothelial cells (HUVECs) were performed to assess
      specific effects of Cox-2 inhibition on platelet adhesion under shear stress (16
      dyn/cm2) and on endothelial release of 6-ketoprostaglandin (PG) F(1alpha).
      Selective inhibition of Cox-2 (NS-398, 0.5 mg/kg) increased platelet adhesion to
      the vessel wall in vivo (11.9+/-3.9 platelets/mm2; controls, 1.4+/-1.4
      platelets/mm2, P<0.05) and platelet adhesion after ADP stimulation in vitro.
      PVWIs were significantly enhanced in NS-398-treated animals, which were reduced
      by platelet pretreatment with aspirin (5 mg/kg) or iloprost (1 nmol/L).
      Inhibition of Cox-2 reduced levels of 6-keto-PGF1alpha in vivo and in HUVEC
      supernatants. Time to occlusion after vessel wall injury was significantly
      shortened by NS-398 (125.4+/-13.6 seconds in NS-398-treated animals versus
      270.8+/-46 seconds in controls; P<0.01). CONCLUSIONS: Selective inhibition of Cox
      2 reduces 6-keto-PGF(1alpha) endothelial release, increases PVWIs, and increases
      firm platelet adhesion in hamster arterioles. Moreover, it leads to faster
      occlusion of damaged microvessels. Thus, selective inhibition of Cox-2 may
      trigger thrombotic events by diminishing the antiplatelet properties of the
      endothelium.

PMID- 15451782
TI  - Natural history and risk stratification of arrhythmogenic right ventricular
      dysplasia/cardiomyopathy.
AB  - BACKGROUND: Management of patients with arrhythmogenic right ventricular
      dysplasia/cardiomyopathy (ARVD/C) is complicated by the incomplete information on
      the natural history of the disease and by the lack of risk stratification for
      cardiovascular death. The aim of the study was the identification of risk factors
      related to long-term prognosis. METHODS AND RESULTS: Data were collected from 130
      patients (100 men; age at onset of symptoms, 31.8+/-14.4 years) from a tertiary
      center between 1977 and 2000 who fulfilled the international standardized
      diagnostic criteria for ARVD/C. Risk factors for cardiovascular death were
      determined by a logistic regression model. After a mean follow-up of 8.1+/-7.8
      years, 24 deaths were recorded, with a mean age at death of 54+/-19 years (annual
      mortality rate, 2.3%). There were 21 deaths with a cardiovascular origin
      (progressive heart failure for 14 patients and sudden death for the remaining 7
      patients). All patients who died had a history of ventricular tachycardia.
      Multivariate analysis showed that after adjustment for sex, history of syncope,
      chest pain, inaugural ventricular tachycardia, recurrence of ventricular
      tachycardia, and QRS dispersion, clinical signs of right ventricular failure and
      left ventricular dysfunction both remained independently associated with
      cardiovascular mortality. The combined presence of one of these risk factors and
      ventricular tachycardia identifies high-risk subjects for cardiovascular
      mortality, whereas patients without ventricular tachycardia displayed the best
      prognosis. CONCLUSIONS: The information on the natural history of patients with
      ARVD allowed us to identify risks factors for cardiovascular mortality. An
      analysis of a large international registry is needed to refine these results.

PMID- 15451783
TI  - Lipoprotein-associated phospholipase A2 adds to risk prediction of incident
      coronary events by C-reactive protein in apparently healthy middle-aged men from
      the general population: results from the 14-year follow-up of a large cohort from
      southern Germany.
AB  - BACKGROUND: Chronic inflammation represents an essential feature of the
      atherosclerotic process. Lipoprotein-associated phospholipase A2 (Lp-PLA2), an
      enzyme mainly produced by monocytes/macrophages, generates potent proinflammatory
      products. METHODS AND RESULTS: Plasma concentrations of Lp-PLA2 were determined
      by ELISA in 934 apparently healthy men aged 45 to 64 years sampled from the
      general population in 1984 and followed up until 1998. During this period, 97 men
      experienced a coronary event diagnosed according to the MONICA (MONItoring of
      trends and determinants in CArdiovascular disease) protocol. Baseline levels of
      Lp-PLA2 were higher in subjects who experienced an event than in event-free
      subjects (295+/-113 versus 263+/-79 ng/mL, P<0.01). Lp-PLA2 was positively
      correlated with total cholesterol (R=0.30, P<0.0001) and age (R=0.12, P=0.001),
      was only slightly correlated with HDL cholesterol (R=0.09, P=0.005) and C
      reactive protein R=0.06, P=0.06), but was not correlated with body mass index or
      blood pressure. In a Cox model, a 1-SD increase in Lp-PLA2 was associated with
      risk of future coronary events (hazard ratio [HR] 1.37, 95% CI 1.16 to 1.62).
      After controlling for potential confounders, the HR was attenuated but remained
      statistically significant (HR 1.23, 95% CI 1.02 to 1.47). Further inclusion of C
      reactive protein in the model did not appreciably affect its predictive ability
      (HR 1.21, 95% CI 1.01 to 1.45). CONCLUSIONS: Elevated levels of Lp-PLA2 appeared
      to be predictive of future coronary events in apparently healthy middle-aged men
      with moderately elevated total cholesterol, independent of CRP. This suggests
      that Lp-PLA2 and CRP may be additive in their ability to predict risk of coronary
      heart disease.

PMID- 15451784
TI  - Growth factors in the collateral circulation of chronic total coronary
      occlusions: relation to duration of occlusion and collateral function.
AB  - BACKGROUND: Despite extensive animal experimental evidence, there are few data on
      the relation of growth factors and collateral function in humans. METHODS AND
      RESULTS: In 104 patients with a chronic total coronary occlusion (CTO; >2 weeks'
      duration), collateral function was assessed invasively during recanalization by
      intracoronary Doppler and pressure recordings. A collateral resistance index,
      R(Coll), was calculated. Blood samples were drawn from the distal coronary bed
      supplied by the collaterals and from the aortic root to measure basic fibroblast
      growth factor (bFGF), monocytic chemotactic protein-1 (MCP-1), transforming
      growth factor-beta (TGF-beta), placenta growth factor (PlGF), and tumor necrosis
      factor-alpha (TNF-alpha). The bFGF concentration in the collateralized artery was
      higher than in the aortic root (34+/-20 versus 18+/-14 pg/mL; P<0.001). bFGF was
      highest in recent occlusions (2 to 12 weeks) with the highest R(Coll). Higher
      collateral concentrations were also observed for MCP-1, TGF-beta, and PlGF, but
      without a close relation to the duration of occlusion. TNF-alpha was not
      increased in collaterals compared with the systemic circulation. MCP-1, PlGF, and
      TGF-beta were significantly increased in small collaterals with the highest shear
      stress. Diabetic patients had lower bFGF and higher MCP-1 levels than
      nondiabetics. CONCLUSIONS: In CTOs, the continuous release of bFGF into
      collaterals showed a close relation to the duration of occlusion and collateral
      function, which underscores its therapeutic potential. Other factors influencing
      growth factor release appeared to be shear stress for MCP-1, TGF-beta, and PlGF
      and the presence of diabetes.

PMID- 15451785
TI  - Critical role of macrophage 12/15-lipoxygenase for atherosclerosis in
      apolipoprotein E-deficient mice.
AB  - BACKGROUND: Mice lacking leukocyte type 12/15-lipoxygenase (12/15-LO) show
      reduced atherosclerosis in several models. 12/15-LO is expressed in a variety of
      cells, including vascular cells, adipocytes, macrophages, and cardiomyocytes. The
      purpose of this study was to determine which cellular source of 12/15-LO is
      important for atherosclerosis. METHODS AND RESULTS: Bone marrow from 12/15-LO-/
      /apoE-/- mice was transplanted into apoE-/- mice and vice versa. Deficiency of
      12/15-LO in bone marrow cells protected apoE-/- mice fed a Western diet from
      atherosclerosis to the same extent as complete absence of 12/15-LO, although
      plasma 8,12-iso-iPF2alpha-IV, a measure of lipid peroxidation, remained elevated.
      12/15-LO-/-/apoE-/- mice regained the severity of atherosclerotic lesion typical
      of apoE-/- mice after replacement of their bone marrow cells with bone marrow
      from apoE-/- mice. Peritoneal macrophages obtained from wild-type but not 12/15
      LO-/- mice caused endothelial activation in the presence of native LDL. Absence
      of 12/15-LO decreased the ability of macrophages to form foam cells when exposed
      to LDL. CONCLUSIONS: We conclude that macrophage 12/15-LO plays a dominant role
      in the development of atherosclerosis by promoting endothelial inflammation and
      foam cell formation.

PMID- 15451786
TI  - Survival after coronary revascularization among patients with kidney disease.
AB  - BACKGROUND: The optimal approach to revascularization in patients with kidney
      disease has not been determined. We studied survival by treatment group (CABG,
      percutaneous coronary intervention [PCI], or no revascularization) for patients
      with 3 categories of kidney function: dialysis-dependent kidney disease, non
      dialysis-dependent kidney disease, and a reference group (serum creatinine <2.3
      mg/dL). METHODS AND RESULTS: Data were derived from the Alberta Provincial
      Project for Outcomes Assessment in Coronary Heart Disease (APPROACH), which
      captures information on all patients undergoing cardiac catheterization in
      Alberta, Canada. Characteristics and patient survival in 662 dialysis patients
      (1.6%) and 750 non-dialysis-dependent kidney disease patients (1.8%) were
      compared with the remainder of the 40,374 patients (96.6%). For the reference
      group, the adjusted 8-year survival rates for CABG, PCI, and no revascularization
      (NR) were 85.5%, 80.4%, and 72.3%, respectively (P<0.001 for CABG versus NR;
      P<0.001 for PCI versus NR). Adjusted survival rates were 45.9% for CABG, 32.7%
      for PCI, and 29.7% for NR in the nondialysis kidney disease group (P<0.001 for
      CABG versus NR; P=0.48 for PCI versus NR) and 44.8% for CABG, 41.2% for PCI, and
      30.4% for NR in the dialysis group (P=0.003 for CABG versus NR; P=0.03 for PCI
      versus NR). CONCLUSIONS: Compared with no revascularization, CABG was associated
      with better survival in all categories of kidney function. PCI was also
      associated with a lower risk of death than no revascularization in reference
      patients and dialysis-dependent kidney disease patients but not in patients with
      non-dialysis-dependent kidney disease. The presence of kidney disease or
      dependence on dialysis should not be a deterrent to revascularization,
      particularly with CABG.

PMID- 15451787
TI  - Sphingosine kinase activation mediates ischemic preconditioning in murine heart.
AB  - BACKGROUND: Phosphorylation of sphingosine by sphingosine kinase (SK) is the rate
      limiting step in the cellular synthesis of sphingosine 1-phosphate (S1P). The
      monoganglioside GM1, which stimulates SK, is cardioprotective in part through
      increased generation of S1P that protects myocytes by diverse mechanisms. Because
      protein kinase C (PKC)epsilon activation is necessary for myocardial ischemic
      preconditioning (IPC) and PKC activators increase SK activity, we tested the
      hypothesis that SK may be a central mediator of IPC. METHODS AND RESULTS: In
      adult murine hearts, IPC sufficient to reduce infarct size significantly
      increased cardiac SK activity, induced translocation of SK protein from the
      cytosol to membranes, and enhanced cardiac myocyte survival. IPC did not increase
      SK activity in PKCepsilon-null mice. The SK antagonist N,N-dimethylsphingosine
      inhibited PKCepsilon activation and directly abolished the protective effects of
      IPC and the enhanced SK activity induced by IPC. CONCLUSIONS: These findings
      demonstrate that PKCepsilon is thus recruited by IPC and induces activation of SK
      that then mediates IPC-induced cardioprotection in murine heart.

PMID- 15451788
TI  - Optimal windows of statin use for immediate infarct limitation: 5'-nucleotidase
      as another downstream molecule of phosphatidylinositol 3-kinase.
AB  - BACKGROUND: Although statins are reported to have a cardioprotective effect,
      their immediate direct influence on ischemia-reperfusion injury and the
      underlying mechanisms remain obscure. We investigated these issues an in vivo
      canine model. METHODS AND RESULTS: Dogs were subjected to coronary occlusion (90
      minutes) and reperfusion (6 hours) immediately after injection of pravastatin
      (0.2, 2, or 10 mg/kg), pitavastatin (0.01, 0.1, or 0.5 mg/kg), or cerivastatin
      (0.5, 5, or 50 microg/kg). Then myocardial phosphatidylinositol 3-kinase (PI3-K)
      and 5'-nucleotidase activities were measured, as well as infarct size. After 15
      minutes of reperfusion, pravastatin caused dose-dependent activation of Akt and
      ecto-5'-nucleotidase in the ischemic zone, and the effect was significant at
      higher doses. Pitavastatin also significantly increased these activities, and its
      optimal dose was within the clinical range, whereas cerivastatin caused
      activation at the lowest dose tested. In all cases, both Akt and ecto-5'
      nucleotidase showed activation in parallel, and this activation was completely
      abolished by wortmannin, a PI3-K inhibitor. The magnitude of the infarct-limiting
      effect paralleled the increase in Akt and ecto-5'-nucleotidase activity and was
      blunted by administration of wortmannin, alpha,beta-methyleneadenosine-5'
      diphosphate, or 8-sulfophenyltheophylline during reperfusion. Both collateral
      flow and the area at risk were comparable for all groups. CONCLUSIONS: Activation
      of ecto-5'-nucleotidase after ischemia by PI3-K activation may be crucial for
      immediate infarct-size limitation by statins. There seems to be an optimal dose
      for each statin that is independent of its clinical cholesterol-lowering effect.

PMID- 15451789
TI  - Exaggerated blood pressure responses during mental stress are prospectively
      related to enhanced carotid atherosclerosis in middle-aged Finnish men.
AB  - BACKGROUND: Hemodynamic reactions to mental stress may contribute to
      atherosclerosis. We previously observed cross-sectional relationships between
      blood pressure reactions to a standardized stress battery and carotid intima
      media thickness (IMT) in the Kuopio Ischemic Heart Disease (KIHD) study. These
      are the first prospective results on this relationship. METHODS AND RESULTS: Men
      from 4 age cohorts (42 to 60 years old at study onset) were challenged with a
      standardized mental stress battery, and heart rate and blood pressure reactions
      were assessed. Ultrasound measures of common carotid IMT were collected at this
      time and 7 years later as noninvasive markers of atherosclerosis. Data were
      collected from a sample of 756 men at both times. Systolic blood pressure
      reactions to mental stress at study onset were positively related to mean carotid
      IMT 7 years later (beta=0.035, P=0.001, by blood pressure quartile, IMT=0.91,
      0.93, 0.96, 1.00 mm) and to the progression of IMT (beta=0.020, P=0.006, by blood
      pressure quartile, DeltaIMT=0.08, 0.09, 0.11, 0.11 mm). Similar significant
      relations were shown for maximal IMT and plaque height. Diastolic blood pressure
      responses were less strongly related to carotid IMT than were systolic responses.
      Heart-rate responses were unrelated. Adjustment for standard risk factors did not
      substantially reduce the relation between systolic blood pressure reactivity and
      the progression of mean carotid IMT (standardized beta=0.059, P=0.026), maximal
      carotid IMT (standardized beta=0.084, P=0.006), or plaque height (standardized
      beta=0.093, P=0.008). CONCLUSIONS: The degree of systolic blood pressure
      reactivity to mental challenge is prospectively related to carotid IMT in middle
      aged and older men, independent of known risk factors.

PMID- 15451790
TI  - Novel associations between bioavailable estradiol and adipokines in elderly women
      with different phenotypes of obesity: implications for atherogenesis.
AB  - BACKGROUND: Peripheral adiposity confers protection against diabetes and
      atherosclerosis in elderly women. The underlying mechanisms, however, remain to
      be elucidated. METHODS AND RESULTS: On the basis on dual-energy X-ray
      absorptiometry measurements of central fat mass (CFM) and peripheral fat mass
      (PFM), we identified 290 elderly women with distinct forms of body fat
      distribution (lean, peripheral obesity, central obesity, or general obesity).
      Study parameters were plasma tumor necrosis factor-alpha, interleukin (IL)-6,
      adiponectin, estradiol, sex hormone-binding globulin, insulin resistance, and
      aortic calcification, graded on lateral radiography. In peripherally and
      generally obese women, plasma estradiol and insulin resistance were significantly
      lower, whereas sex hormone-binding globulin and adiponectin were significantly
      higher compared with centrally obese women independent of age, body mass index,
      total fat mass, and smoking habits (all P<0.05). After adjustment for these
      confounders, IL-6 in centrally obese women was comparable with that seen in
      generally obese (similar high CFM%) but significantly higher than in peripherally
      obese women and lean women (low CFM%). Atherosclerosis was less severe in
      generally obese (2.5+/-0.3) compared with centrally obese women (5.0+/-0.7,
      P=0.001). In multiple regression analysis, total fat mass, body fat distribution,
      insulin resistance, estradiol, current smoking, treated hyperlipidemia, and
      treated hypertension contributed independently to the variation of aortic
      calcification (R=0.55, SEE=3.60, P<0.001). CONCLUSIONS: Abundant presence of PFM
      in generally obese women is associated with increased plasma adiponectin and
      higher insulin sensitivity, which could explain the apparent protection against
      the atherogenic effects of IL-6 derived from CFM. Low peripheral exposure to
      estradiol appears to be a sine qua non of maintained adiponectin secretion from
      PFM.

PMID- 15451791
TI  - Genetically determined resistance to collagenase action augments interstitial
      collagen accumulation in atherosclerotic plaques.
AB  - BACKGROUND: We hypothesized that collagenolytic activity produced by activated
      macrophages contributes to collagen loss and the subsequent instability of
      atheromatous lesions, a common trigger of acute coronary syndromes. However, no
      direct in vivo evidence links collagenases with the regulation of collagen
      content in atherosclerotic plaques. METHODS AND RESULTS: To test the hypothesis
      that collagenases influence the structure of atheromata, we examined collagen
      accumulation in atherosclerotic lesions of apolipoprotein E-deficient mice (apoE
      /-) that express collagenase-resistant collagen-I (ColR/R/apoE-/-, n=12) or wild
      type collagen-expressing mice (Col+/+/apoE-/-, n=12). Aortic atheromata of both
      groups had similar sizes and numbers of macrophages, a major source of
      collagenases. However, aortic intimas from ColR/R/apoE-/- mice contained fewer
      smooth muscle cells, a source of collagen, probably because of decreased
      migration or proliferation or increased cell death. Despite reduced numbers of
      smooth muscle cells, atheromata of ColR/R/apoE-/- mice contained significantly
      more intimal collagen than did those of Col+/+/apoE-/- mice. CONCLUSIONS: These
      results establish that collagenase action regulates plaque collagen turnover and
      smooth muscle cell accumulation.

PMID- 15451792
TI  - Left ventricular remodeling and heart failure in diabetic patients treated with
      primary angioplasty for acute myocardial infarction.
AB  - BACKGROUND: Diabetes mellitus has been recognized as a strong predictor of heart
      failure (HF) in patients with acute myocardial infarction (AMI). However,
      considerable controversy exists regarding the pathogenetic mechanisms of HF after
      AMI in diabetic patients. We hypothesized that the increased incidence of HF in
      diabetic patients was associated with a greater propensity for left ventricular
      (LV) remodeling. METHODS AND RESULTS: A series of 325 patients (42 diabetics)
      with AMI successfully treated with primary angioplasty underwent serial 2D
      echocardiography from admission to 1 and 6 months and 6-month angiography. No
      significant difference was found between diabetics and nondiabetics regarding
      baseline clinical, angiographic, and echocardiographic characteristics, as well
      as 6-month restenosis and reocclusion rates. At 6 months, a similar incidence of
      LV remodeling was observed in diabetics and nondiabetics (33% versus 25%;
      P=0.234), with similar patterns of changes in LV volumes and LV global and
      regional systolic function. At 5 years, the incidence of HF was higher in the
      diabetics (43% versus 20%, P=0.001). Diabetes was found to be an independent
      predictor of HF at 5 years (hazard ratio, 1.8; P=0.0366). However, LV remodeling
      was predictive of HF in the nondiabetics (P=0.023) but not in the diabetics
      (P=0.123). In a subgroup of patients, higher LV chamber stiffness (as assessed by
      echocardiography) was detected in the diabetics with HF. CONCLUSIONS: The more
      frequent progression to HF in the diabetics after AMI is not explained by a
      greater propensity for LV remodeling. Other factors, such as diastolic
      dysfunction, may play a role.

PMID- 15451793
TI  - ACAT2 is localized to hepatocytes and is the major cholesterol-esterifying enzyme
      in human liver.
AB  - BACKGROUND: Two acyl-coenzyme A:cholesterol acyltransferase (ACAT) genes, ACAT1
      and ACAT2, have been identified that encode 2 proteins responsible for
      intracellular cholesterol esterification. METHODS AND RESULTS: In this study,
      immunohistology was used to establish their cellular localization in human liver
      biopsies. ACAT2 protein expression was confined to hepatocytes, whereas ACAT1
      protein was found in Kupffer cells only. Studies with a highly specific ACAT2
      inhibitor, pyripyropene A, in microsomal activity assays demonstrated that ACAT2
      activity was highly variable among individual human liver samples, whereas ACAT1
      activity was more similar in all specimens. ACAT2 provided the major cholesterol
      esterifying activity in 3 of 4 human liver samples examined. CONCLUSIONS: The
      data suggest that in diseases in which dysregulation of cholesterol metabolism
      occurs, such as hypercholesterolemia and atherosclerosis, ACAT2 should be
      considered a target for prevention and treatment.

PMID- 15451794
TI  - Prognostic value of systemic endothelial dysfunction in patients with acute
      coronary syndromes: further evidence for the existence of the "vulnerable"
      patient.
AB  - BACKGROUND: Endothelial vasodilator dysfunction may serve as a marker integrating
      the vascular risk of an individual; however, whether systemic vasodilator
      function predicts disease progression and cardiovascular event rates in patients
      with manifest acute coronary syndromes (ACS) is unknown. METHODS AND RESULTS: In
      198 patients with angiographically documented ACS, forearm blood flow (FBF)
      responses to acetylcholine (ACH; 10 to 50 microg/min) and sodium nitroprusside
      (SNP; 2 to 8 microg/min) were measured by venous occlusion plethysmography before
      hospital discharge within 5 days of an episode of an ACS. Cardiovascular events
      (cardiovascular death, myocardial infarction, and ischemic stroke) served as
      outcome variables over a mean follow-up period of 47.7+/-15.1 months. Patients
      who experienced cardiovascular events during follow-up (n=31) had a significantly
      reduced vasodilator response to ACH (P<0.05) and SNP (P<0.05). By multivariate
      analysis, vasodilator response to ACH and elevated troponin T serum levels were
      the only significant (P<0.05) independent predictors of a poor prognosis, even
      after adjustment for traditional cardiovascular risk factors, concurrent
      medication, invasive treatment strategy, and C-reactive protein serum levels.
      Recovery of endothelium-dependent vasoreactivity as assessed by repeated FBF
      assessment 8 weeks after the index measurement after the ACS predicted further
      event-free survival in a subset of 78 patients. CONCLUSIONS: Systemic endothelium
      dependent vasoreactivity predicts recurrence of instability and cardiovascular
      event rates in patients with ACS. Furthermore, the recovery of systemic
      endothelial function is associated with event-free survival. Assessment of
      systemic vasoreactivity, measured by a minimally invasive test, provides
      important prognostic information in addition to that derived from traditional
      risk factor assessment in patients with ACS.

PMID- 15451795
TI  - Medical costs and quality of life 10 to 12 years after randomization to
      angioplasty or bypass surgery for multivessel coronary artery disease.
AB  - BACKGROUND: Coronary bypass surgery (CABG) and angioplasty (PTCA) have been
      compared in several randomized trials, but data about long-term economic and
      quality-of-life outcomes are limited. METHODS AND RESULTS: Cost and quality-of
      life data were collected prospectively from 934 patients who were randomized in
      the Bypass Angioplasty Revascularization Investigation (BARI) and followed up for
      10 to 12 years. CABG had 53% higher costs initially, but the gap closed to <5%
      during the first 2 years; after 12 years, the mean cumulative cost of CABG
      patients was 123,000 dollars versus 120,750 dollars for PTCA, yielding a cost
      effectiveness ratio of 14,300 dollars/life-year added. CABG patients experienced
      significantly greater improvement in their physical functioning for the first 3
      years but not in later follow-up. Recurrent angina substantially reduced all
      quality-of-life measures throughout follow-up. Cumulative costs were
      significantly higher among patients with diabetes, heart failure, and comorbid
      conditions and among women; costs also were increased by angina, by the number of
      revascularization procedures, and among patients who died. CONCLUSIONS: Early
      differences between CABG and PTCA in costs and quality of life were no longer
      significant at 10 to 12 years of follow-up. CABG was cost-effective as compared
      with PTCA for multivessel disease.

PMID- 15451796
TI  - Angiotensin receptor blockade with candesartan attenuates atherosclerosis, plaque
      disruption, and macrophage accumulation within the plaque in a rabbit model.
AB  - BACKGROUND: Little is known about whether direct angiotensin receptor blockade
      can reduce atherosclerosis and plaque disruption. This study evaluated the effect
      of angiotensin receptor blockade on both the development of atherosclerosis and
      the disruption of plaque in a modified Constantinides animal model. METHODS AND
      RESULTS: Twenty-eight New Zealand White rabbits underwent aortic balloon injury
      followed by a 1% cholesterol diet for 8 weeks. Thirteen rabbits received
      candesartan at 0.5 mg x kg(-1) x d(-1) beginning 2 days before aortic balloon
      injury and continued for the total 8 weeks of the cholesterol diet. The rabbits
      were then pharmacologically triggered and humanely killed, and their aortas were
      analyzed. The degree of atherosclerosis was determined by intima-media ratio of
      the infrarenal portion of the aorta. The frequency of intra-aortic thrombosis, a
      measure of plaque disruption, and the percentages of macrophage area and collagen
      staining area of the plaque were determined. Candesartan-treated rabbits had less
      atherosclerosis (intima-media infrarenal aorta ratio of 1.18+/-0.08 versus 1.57+/
      0.08 [mean+/-SEM] for the placebo group, P<0.001); fewer thrombi (3 of 13 versus
      11 of 15; P<0.05); lower percentage area of macrophages to total plaque (18.8+/
      2.7% versus 27+/-2.5%, P<0.05); and higher collagen to total plaque area (45+/-3%
      versus 35+/-2%, P<0.01). CONCLUSIONS: These results demonstrate that angiotensin
      receptor blockade attenuates the degree of atherosclerosis and reduces both
      plaque disruption and macrophage accumulation while increasing collagen
      deposition in the aortas of this animal model.

PMID- 15451797
TI  - N-acetylcysteine treatment normalizes serum tumor necrosis factor-alpha level and
      hinders the progression of cardiac injury in hypertensive rats.
AB  - BACKGROUND: Studies in isolated cardiomyocytes showed that replenishment in
      cellular glutathione, achieved with the glutathione precursor N-acetylcysteine
      (NAC), abrogated deleterious effects of tumor necrosis factor-alpha (TNF-alpha).
      METHODS AND RESULTS: We examined the ability of NAC to limit the progression of
      cardiac injury in the rat model of hypertension, induced by the nitric oxide
      synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) (50 mg/kg per day
      SC) and high-salt diet (HS) (8% NaCl). Four-week HS/L-NAME administration induced
      hypertension (193+/-8 versus 122+/-4 mm Hg for low-salt diet [LS] group) and left
      ventricular (LV) dysfunction, revealed by echocardiography and characterized by
      decreased LV shortening fraction (38+/-2% versus 49+/-4% for LS group; P<0.05)
      and decreased LV posterior wall thickening (49+/-3% versus 70+/-4% for LS group;
      P<0.05). LV dysfunction worsened further after 6-week HS/L-NAME administration.
      Importantly, increase in serum TNF-alpha level was strongly correlated with
      shortening fraction decrease and cardiac glutathione depletion. NAC (75 mg/d) was
      given as a therapeutic treatment in a subgroup of HS/L-NAME animals during weeks
      5 and 6 of HS/L-NAME administration. NAC treatment, which replenished cardiac
      glutathione, had no effect on hypertension but reduced LV remodeling and
      dysfunction, normalized serum TNF-alpha level, and limited activation of matrix
      metalloproteinases -2 and -9 and collagen deposition in LV tissues. CONCLUSIONS:
      These findings suggest that glutathione status determines the adverse effects of
      TNF-alpha in cardiac failure and that TNF-alpha antagonism may be achieved by
      glutathione supplementation.

PMID- 15451798
TI  - Relation of nonperfused myocardial volume and surface area to left ventricular
      performance in coronary microembolization.
AB  - BACKGROUND: After occlusion of an epicardial artery, left ventricular (LV)
      dysfunction is closely related to the volume of nonperfused myocardium (NPM). The
      impact of coronary microembolization (ME) on LV function, however, is larger
      relative to the total volume of NPM. We hypothesized that the total surface area
      (SA), rather than the total volume, of NPM is the major determinant of ME-induced
      LV dysfunction. METHODS AND RESULTS: We injected microspheres of 10-, 30-, or 100
      microm diameter at each of 3 doses selectively into the left anterior descending
      coronary artery of 48 anesthetized pigs. Electron beam computed tomography (CT)
      was used to measure regional myocardial perfusion and changes in LV wall
      thickening (DeltaWT) and stroke volume (DeltaSV) after ME. At postmortem, a
      transmural "biopsy" of 1 to 2 cm3 of embolized myocardium was imaged by micro-CT,
      resulting in 3D images that provided volumes and SAs of the individual
      nonperfused foci. Additionally, in 9 pigs, creatine phosphokinase (CK) activity
      in embolized myocardium was measured as an index of washout of substances from
      the NPM. After ME, DeltaWT, DeltaSV, and CK washout were correlated more closely
      with the total SA (r=0.95, P<0.001; r=0.68, P<0.01; and r=0.88, P=0.01,
      respectively) than with the total NPM volume (r=0.59, P>0.05; 0.46, P>0.05; and
      r=0.69, P=0.04, respectively). CONCLUSIONS: After coronary ME, LV dysfunction is
      more closely related to the total SA than to the total volume of nonperfused
      microregions in the myocardium.

PMID- 15451799
TI  - Cytokine-induced mobilization of circulating endothelial progenitor cells
      enhances repair of injured arteries.
AB  - BACKGROUND: The existence of circulating endothelial progenitor cells (CEPCs) has
      previously been documented. These cells can be mobilized by cytokines and are
      recruited to sites of injury, where they may participate in tissue repair. In the
      present study, we examined the hypothesis that mobilization of CEPCs by exogenous
      granulocyte-colony stimulating factor (G-CSF) enhances repair of injured arteries
      by facilitating reendothelialization and inhibiting neointima development.
      METHODS AND RESULTS: Male rats were injected daily with 50 microg/kg recombinant
      human G-CSF or 0.9% NaCl SC for 8 days. On the fifth day of treatment, 1 mL of
      blood was collected for fluorescence-activated cell sorting analysis of
      mononuclear cells, and the animals underwent balloon angioplasty of the common
      carotid artery. The animals were killed at 2 or 4 weeks after injury, and the
      carotid arteries were harvested and processed for immunohistochemistry, scanning
      electron microscopy (SEM), and morphometric analysis of endothelialization and
      neointimal formation. G-CSF increased the number of circulating mononuclear cells
      that express endothelial cell lineage markers several-fold. SEM and
      immunohistochemical staining with the endothelial marker, platelet and
      endothelial cell adhesion molecule-1, showed rapid and nearly complete (>90%)
      reendothelialization of the denuded vessels in the G-CSF-treated animals compared
      with <20% in the control animals. Reendothelialization was paralleled by a
      decrease in inflammation in the vessel wall. Neointima thickness was reduced by
      approximately 60% in the G-CSF-treated animals compared with control animals at 2
      and 4 weeks after injury. CONCLUSIONS: We postulate that cytokine-induced
      mobilization of CEPCs may be a suitable therapeutic strategy for prevention of
      restenosis after revascularization procedures.

PMID- 15451800
TI  - N-terminal-pro-brain natriuretic peptide predicts outcome after hospital
      discharge in heart failure patients.
AB  - BACKGROUND: Heart failure (HF) is responsible for a huge burden in hospital care.
      Our goal was to evaluate the value of N-terminal-pro-brain natriuretic peptide
      (NT-proBNP) in predicting death or hospital readmission after discharge of HF
      patients. METHODS AND RESULTS: We included 182 patients consecutively admitted to
      hospital because of decompensated HF. Patients were followed up for 6 months. The
      primary end point was death or readmission. Twenty-six patients died in hospital.
      The median admission NT-proBNP level was 6778.5 pg/mL, and the median level at
      discharge was 4137.0 pg/mL (P<0.001). Patients were classified into 3 groups: (1)
      decreasing NT-proBNP levels by at least 30% (n=82), (2) no significant
      modifications on NT-proBNP levels (n=49), and (3) increasing NT-proBNP levels by
      at least 30% (n=25). The primary end point was observed in 42.9% patients.
      Variables associated with an increased hazard of death and/or hospital
      readmission in univariate analysis were length of hospitalization, heart rate,
      signs of volume overload, no use of ACE inhibitors, higher NYHA class at
      discharge, admission and discharge NT-proBNP, and the change in NT-proBNP levels.
      The variation in NT-proBNP was the strongest predictor of an adverse outcome.
      Independent variables associated with an increased risk of readmission or death
      were signs of volume overload and the change in NT-proBNP levels. CONCLUSIONS:
      Variations in NT-proBNP levels are related to hospital readmission and death
      within 6 months. NT-proBNP levels are potentially useful in the evaluation of
      treatment efficacy and might help clinicians in planning discharge of HF
      patients. Whether therapeutic strategies aimed to lower NT-proBNP levels modify
      prognosis warrants future investigation.

PMID- 15451801
TI  - Magnetic resonance imaging analysis of right ventricular pressure-volume loops:
      in vivo validation and clinical application in patients with pulmonary
      hypertension.
AB  - BACKGROUND: The aims of this study were to validate MRI-derived right ventricular
      (RV) pressure-volume loops for assessment of RV myocardial contractility and then
      to apply this technique in patients with chronic RV pressure overload for
      assessment of myocardial contractility, ventricular pump function, and VA
      coupling. METHODS AND RESULTS: Flow-directed catheters were guided under MR
      fluoroscopy (1.5 T) into the RV for invasive pressure measurements.
      Simultaneously, ventricular volumes and myocardial mass were assessed from cine
      MRI. From sampled data, RV pressure-volume loops were constructed, and maximal
      ventricular elastance indexed to myocardial mass (E(max_i)) was derived by use of
      a single-beat estimation method. This MRI method was first validated in vivo (6
      swine), with conductance techniques used as reference. Bland-Altman test showed
      good agreement between methods (E(max_i)=5.1+/-0.5 versus 5.8+/-0.7 mm Hg x mL(
      1) x 100 g(-1), respectively; P=0.08). Subsequently, the MRI method was applied
      in 12 subjects: 6 control subjects and 6 patients with chronic RV pressure
      overload from pulmonary hypertension. In these patients, indexes of RV pump
      function (cardiac index), E(max_i), and VA coupling (E(max)/E(a)) were assessed.
      In patients with pulmonary hypertension, RV pump function was decreased (cardiac
      index, 2.2+/-0.5 versus 2.9+/-0.4 L x min(-1) x m(-2); P<0.01), myocardial
      contractility was enhanced (E(max_I), 9.2+/-1.1 versus 5.0+/-0.9 mm Hg x mL(-1) x
      100 g(-1); P<0.01), and VA coupling was inefficient (E(max)/E(a), 1.1+/-0.3
      versus 1.9+/-0.4; P<0.01) compared with control subjects. CONCLUSIONS: RV
      myocardial contractility can be determined from MRI-derived pressure-volume
      loops. Chronic RV pressure overload was associated with reduced RV pump function
      despite enhanced RV myocardial contractility. The proposed MRI approach is a
      promising tool to assess RV contractility in the clinical setting.

PMID- 15451802
TI  - Comorbidity and myocardial dysfunction are the main explanations for the higher 1
      year mortality in acute myocardial infarction with left bundle-branch block.
AB  - BACKGROUND: The purpose of this study was to assess the independent contribution
      of left bundle-branch block (LBBB) on cause-specific 1-year mortality in a large
      cohort with acute myocardial infarction (MI). METHODS AND RESULTS: We studied a
      prospective cohort of 88,026 cases of MI from the Register of Information and
      Knowledge about Swedish Heart Intensive care Admissions in 72 hospitals in 1995
      to 2001. Long-term mortality was calculated by Cox regression analysis, adjusted
      for multiple covariates that affect mortality by calculation of a propensity
      score. LBBB was present in 9% (8041 of 88,026) of the MI admissions. Patients
      with LBBB were older and had a higher prevalence of comorbid conditions than
      patients with no LBBB. The unadjusted relative risk of death within 1 year was
      2.16 (95% CI, 2.08 to 2.24; P<0.001) for LBBB (42%, 3350 of 8041) compared with
      those with no LBBB (22%, 17,044 of 79,011). After adjustment for a propensity
      score that takes into account differences in risk factors and acute intervention,
      LBBB was associated with a relative risk of death of 1.19 (95% CI, 1.14 to 1.24;
      P<0.001). In a subgroup of 11,812 patients for whom left ventricular ejection
      fraction was available and could be added to the analysis, the contributing
      relative risk of LBBB for death was only 1.08 (95% CI, 0.93 to 1.25; P=0.33). The
      most common cause of death in both groups was ischemic heart disease.
      CONCLUSIONS: MI patients with LBBB have more comorbid conditions and an increased
      unadjusted 1-year mortality. When adjusted for age, baseline characteristics,
      concomitant diseases, and left ventricular ejection fraction, LBBB does not
      appear to be an important independent predictor of 1-year mortality in MI.

PMID- 15451803
TI  - Impact of prehospital thrombolysis for acute myocardial infarction on 1-year
      outcome: results from the French Nationwide USIC 2000 Registry.
AB  - BACKGROUND: Limited data are available on the impact of prehospital thrombolysis
      (PHT) in the "real-world" setting. METHODS AND RESULTS: Of 443 intensive care
      units in France, 369 (83%) prospectively collected all cases of infarction (< or
      =48 hours of symptom onset) in November 2000; 1922 patients (median age, 67
      years; 73% men) with ST-segment-elevation infarction were included, of whom 180
      (9%) received intravenous thrombolysis before hospital admission (PHT). Patients
      with PHT were younger than those with in-hospital thrombolysis, primary
      percutaneous interventions, or no reperfusion therapy. Median time from symptom
      onset to hospital admission was 3.6 hours for PHT, 3.5 hours for in-hospital
      lysis, 3.2 hours for primary percutaneous interventions, and 12 hours for no
      reperfusion therapy. In-hospital death was 3.3% for PHT, 8.0% for in-hospital
      lysis, 6.7% for primary percutaneous interventions, and 12.2% for no reperfusion
      therapy. One-year survival was 94%, 89%, 89%, and 79%, respectively. In a
      multivariate analysis of predictors of 1-year survival, PHT was associated with a
      0.49 relative risk of death (95% CI, 0.24 to 1.00; P=0.05). When the analysis was
      limited to patients receiving reperfusion therapy, the relative risk of death for
      PHT was 0.52 (95% CI, 0.25 to 1.08; P=0.08). In patients with PHT admitted in <
      or =3.5 hours, in-hospital mortality was 0% and 1-year survival was 99%.
      CONCLUSIONS: The 1-year outcome of patients treated with PHT compares favorably
      with that of patients treated with other modes of reperfusion therapy; this
      favorable trend persists after multivariate adjustment. Patients with PHT
      admitted very early have a very high 1-year survival rate.

PMID- 15451804
TI  - Microvolt T-wave alternans distinguishes between patients likely and patients not
      likely to benefit from implanted cardiac defibrillator therapy: a solution to the
      Multicenter Automatic Defibrillator Implantation Trial (MADIT) II conundrum.
AB  - BACKGROUND: In 2003, the Centers for Medicaid and Medicare Services recommended
      QRS duration as a means to identify MADIT II-like patients suitable for implanted
      cardiac defibrillator (ICD) therapy. We compared the ability of microvolt T-wave
      alternans and QRS duration to identify groups at high and low risk of dying among
      heart failure patients who met MADIT II criteria for ICD prophylaxis. METHODS AND
      RESULTS: Patients with MADIT II characteristics and sinus rhythm had a microvolt
      T-wave alternans exercise test and a 12-lead ECG. Our primary end point was 2
      year all-cause mortality. Of 177 MADIT II-like patients, 32% had a QRS duration
      >120 ms, and 68% had an abnormal (positive or indeterminate) microvolt T-wave
      alternans test. During an average follow-up of 20+/-6 months, 20 patients died.
      We compared patients with an abnormal microvolt T-wave alternans test to those
      with a normal (negative) test, and patients with a QRS >120 ms with those with a
      QRS < or =120 ms; the hazard ratios for 2-year mortality were 4.8 (P=0.020) and
      1.5 (P=0.367), respectively. The actuarial mortality rate was substantially lower
      among patients with a normal microvolt T-wave alternans test (3.8%; 95%
      confidence interval: 0, 9.0) than the mortality rate in patients with a narrow
      QRS (12.0%; 95% confidence interval: 5.6, 18.5). The corresponding false-negative
      rates are 3.5% and 10.2%, respectively. CONCLUSIONS: Among MADIT II-like
      patients, a microvolt T-wave alternans test is better than QRS duration at
      identifying a high-risk group and also better at identifying a low-risk group
      unlikely to benefit from ICD therapy.

PMID- 15451805
TI  - Recombinant human antibodies against aldehyde-modified apolipoprotein B-100
      peptide sequences inhibit atherosclerosis.
AB  - BACKGROUND: Accumulation and oxidation of LDL are believed to be important
      initiating factors in atherosclerosis. Oxidized LDL is recognized by the immune
      system, and animal studies have suggested that these immune responses have a
      protective effect against atherosclerosis. Aldehyde-modified peptide sequences in
      apolipoprotein B-100 (apoB-100) are major targets for these immune responses.
      METHODS AND RESULTS: Human IgG1 antibodies against 2 malondialdehyde (MDA)
      modified apoB-100 peptide sequences were produced through screening of a single
      chain antibody-fragment library and subsequent cloning into a pcDNA3 vector.
      Three weekly doses of these antibodies were injected into male apoE-/- mice.
      Phosphate-buffered saline and human IgG1 antibodies against fluorescein
      isothiocyanate were used as controls. One of the IgG1 antibodies significantly
      and dose-dependently reduced the extent of atherosclerosis as well as the plaque
      content of oxidized LDL epitopes and macrophages. In cell culture studies, human
      monocytes were incubated with native LDL or oxidized LDL, in the presence of
      antibodies. The same antibody induced an increase in monocyte binding and uptake
      of oxidized LDL. CONCLUSIONS: These findings suggest that antibodies are
      important mediators of atheroprotective immune responses directed to oxidized
      LDL. Thus, passive immunization against MDA-modified apoB-100 peptide sequences
      may represent a novel therapeutic approach for prevention and treatment of
      cardiovascular disease.

PMID- 15451806
TI  - Neurocardiac interaction during stress-induced myocardial ischemia: how does the
      brain cope?

PMID- 15451807
TI  - A new HOPE for aldosterone blockade?

PMID- 15451808
TI  - Genetic basis of atherosclerosis: part I: new genes and pathways.

PMID- 15451809
TI  - Images in cardiovascular medicine. Catheter closure of pseudoaneurysm of the main
      pulmonary artery.

PMID- 15451810
TI  - Images in cardiovascular medicine. Heart within a heart: contrast 3-dimensional
      echocardiography imaging of a tricuspid valve blood cyst.

PMID- 15451811
TI  - Vascular anomalies in Alagille syndrome.

PMID- 15451812
TI  - Overestimation of plasma nonesterified fatty acid concentrations in heparinized
      blood.

PMID- 15451813
TI  - Polymorphism of inhibitory renin-angiotensin system as a genetic risk factor for
      atrial fibrillation.

PMID- 15451814
TI  - Leptin, C-reactive protein, and nitric oxide production in healthy humans.

PMID- 15451815
TI  - Role of paradoxic embolism in patients with acute pulmonary embolism and right
      ventricular enlargement who are at risk for adverse clinical events.

PMID- 15451816
TI  - Is green tea better than black tea in reducing atherosclerosis?

PMID- 15451817
TI  - The Cochrane Collaboration at 10: kudos and challenges.

PMID- 15451818
TI  - Preparing physicians for the real world.

PMID- 15451821
TI  - TB and adrenal insufficiency.

PMID- 15451823
TI  - Privacy of pharmacy prescription records.

PMID- 15451825
TI  - Quebec to report on Clostridium difficile in 2005.

PMID- 15451826
TI  - From CMJ to CMAJ.

PMID- 15451827
TI  - Telemedicine: on, under and out of this world.

PMID- 15451828
TI  - US Medicare opens door to covering obesity treatments.

PMID- 15451829
TI  - ALLHAT: what has it taught us so far?

PMID- 15451830
TI  - Antibiotics for sore throat to prevent rheumatic fever: yes or no? How the
      Cochrane Library can help.

PMID- 15451831
TI  - Fall prevention in the elderly population.

PMID- 15451832
TI  - Domperidone for lactating women.

PMID- 15451833
TI  - Volvulus: a rare twist on small-bowel obstruction.

PMID- 15451834
TI  - Changes in public order after the opening of a medically supervised safer
      injecting facility for illicit injection drug users.
AB  - BACKGROUND: North America's first medically supervised safer injecting facility
      for illicit injection drug users was opened in Vancouver on Sept. 22, 2003.
      Although similar facilities exist in a number of European cities and in Sydney,
      Australia, no standardized evaluations of their impact have been presented in the
      scientific literature. METHODS: Using a standardized prospective data collection
      protocol, we measured injection-related public order problems during the 6 weeks
      before and the 12 weeks after the opening of the safer injecting facility in
      Vancouver. We measured changes in the number of drug users injecting in public,
      publicly discarded syringes and injection-related litter. We used Poisson log
      linear regression models to evaluate changes in these public order indicators
      while considering potential confounding variables such as police presence and
      rainfall. RESULTS: In stratified linear regression models, the 12-week period
      after the facility's opening was independently associated with reductions in the
      number of drug users injecting in public (p < 0.001), publicly discarded syringes
      (p < 0.001) and injection-related litter (p < 0.001). The predicted mean daily
      number of drug users injecting in public was 4.3 (95% confidence interval [CI]
      3.5-5.4) during the period before the facility's opening and 2.4 (95% CI 1.9-3.0)
      after the opening; the corresponding predicted mean daily numbers of publicly
      discarded syringes were 11.5 (95% CI 10.0-13.2) and 5.4 (95% CI 4.7-6.2).
      Externally compiled statistics from the city of Vancouver on the number of
      syringes discarded in outdoor safe disposal boxes were consistent with our
      findings. INTERPRETATION: The opening of the safer injecting facility was
      independently associated with improvements in several measures of public order,
      including reduced public injection drug use and public syringe disposal.

PMID- 15451835
TI  - Outcome reporting bias in randomized trials funded by the Canadian Institutes of
      Health Research.
AB  - BACKGROUND: The reporting of outcomes within published randomized trials has
      previously been shown to be incomplete, biased and inconsistent with study
      protocols. We sought to determine whether outcome reporting bias would be present
      in a cohort of government-funded trials subjected to rigorous peer review.
      METHODS: We compared protocols for randomized trials approved for funding by the
      Canadian Institutes of Health Research (formerly the Medical Research Council of
      Canada) from 1990 to 1998 with subsequent reports of the trials identified in
      journal publications. Characteristics of reported and unreported outcomes were
      recorded from the protocols and publications. Incompletely reported outcomes were
      defined as those with insufficient data provided in publications for inclusion in
      meta-analyses. An overall odds ratio measuring the association between
      completeness of reporting and statistical significance was calculated stratified
      by trial. Finally, primary outcomes specified in trial protocols were compared
      with those reported in publications. RESULTS: We identified 48 trials with 68
      publications and 1402 outcomes. The median number of participants per trial was
      299, and 44% of the trials were published in general medical journals. A median
      of 31% (10th-90th percentile range 5%-67%) of outcomes measured to assess the
      efficacy of an intervention (efficacy outcomes) and 59% (0%-100%) of those
      measured to assess the harm of an intervention (harm outcomes) per trial were
      incompletely reported. Statistically significant efficacy outcomes had a higher
      odds than nonsignificant efficacy outcomes of being fully reported (odds ratio
      2.7; 95% confidence interval 1.5-5.0). Primary outcomes differed between
      protocols and publications for 40% of the trials. INTERPRETATION: Selective
      reporting of outcomes frequently occurs in publications of high-quality
      government-funded trials.

PMID- 15451836
TI  - Limitations to antiarrhythmic drug use in patients with atrial fibrillation.
AB  - BACKGROUND: Of the antiarrhythmic agents currently marketed in Canada, 5 are
      commonly used to treat atrial fibrillation (AF). The impact of contraindications,
      warnings and precautions for the use of these drugs in patients with AF is not
      known. We evaluated the proportion of patients with AF for whom
      contraindications, warnings and/or precautions might limit the use of these
      commonly prescribed drugs and the proportion of patients actually receiving
      antiarrhythmic drugs despite the presence of contraindications and/or warnings.
      METHODS: A total of 723 patients with electrocardiographically confirmed, new
      onset paroxysmal AF who were enrolled in the Canadian Registry of Atrial
      Fibrillation were used in this analysis. The 1996 Compendium of Pharmaceuticals
      and Specialties was used to obtain contraindications, warnings and precautions
      for use of 5 antiarrhythmic drugs: flecainide, quinidine, sotalol, amiodarone and
      propafenone. Proportions of patients with contraindications, warnings and/or
      precautions for use of any of these drugs owing to comorbid conditions or
      concomitant drug therapy were calculated, regardless of whether the drugs had
      been prescribed. We then calculated the proportion of patients taking each
      antiarrhythmic drug at 3 months despite contraindications and/or warnings.
      RESULTS: At baseline, when conditions for contraindications and warnings were
      combined, 414 (57%), 235 (33%), 327 (45%), 285 (39%) and 272 (38%) patients had
      restrictions for the use of flecainide, quinidine, sotalol, amiodarone and
      propafenone respectively. Among 465 patients actually taking these medications at
      3-month follow-up, 33.3% (2/6), 83.3% (40/48), 36.4% (92/253), 64.1% (25/39) and
      34.5% (41/119) respectively had contraindications and/or warnings against their
      use. The burden of comorbid disease among patients with AF was noteworthy: 404
      (56%) had structural heart disease, which included 227 (31%) with ischemic heart
      disease, 158 (22%) with left ventricular systolic dysfunction and 106 (15%) with
      heart failure. INTERPRETATION: The high burden of comorbid disease and
      concomitant drug use in a large proportion of patients with AF limits the
      suitability of existing antiarrhythmic drugs. Over one-third of patients with new
      onset AF received antiarrhythmic drugs despite the presence of contraindications
      or warnings. Although such restrictions may not preclude the use of these drugs,
      the results demonstrate the need for new antiarrhythmic drugs with fewer
      limitations.

PMID- 15451837
TI  - So what has the Cochrane Collaboration ever done for us? A report card on the
      first 10 years.

PMID- 15451838
TI  - Registering CIHR-funded randomized controlled trials: a global public good.

PMID- 15451839
TI  - Antiarrhythmic drugs for atrial fibrillation: Do we need better use, better drugs
      or a randomized trial of ablation as primary therapy?

PMID- 15451840
TI  - Atrial fibrillation.
AB  - Atrial fibrillation (AF) is the most common sustained dysrhythmia in adults. It
      is ironic, then, that although mechanisms and effective treatments for most other
      supraventricular tachyarrhythmias have been discovered, AF remains incompletely
      understood and poorly treated. Nonetheless, our understanding of the
      pathophysiology of AF has improved in the last half-century, including some
      groundbreaking observations made in the last 10 years. Indeed, for some patients,
      the potential for cure now appears to be available. Because no unifying mechanism
      of AF has been proven, the aim of this review is to describe some of the common
      and important concepts behind current mechanistic theories of AF and how they
      contribute to our clinical understanding of AF.

PMID- 15451841
TI  - Nouns and verbs in Australian sign language: an open and shut case?
AB  - Results of the noun-verb pair comprehension and production tests from the Test
      Battery for Auslan Morphology and Syntax (Schembri et al., 2000) are re
      presented, re-analyzed, and compared to data from two other cases also dealing
      with noun-verb pairs: the Auslan lexical database and a comparison of Auslan and
      American Sign Language (ASL) signs. The data elicited through the test battery
      and presented in this article confirm the existence of formationally related noun
      verb pairs in Auslan in which the verb displays a single movement and the noun
      displays a repeated movement. The data also suggest that the best exemplars of
      noun-verb pairs of this type in Auslan form a distinct set of iconic (mimetic)
      signs archetypically based on inherently reversible actions (such as opening and
      shutting). This strong iconic link perhaps explains why the derivational process
      appears to be of limited productivity, though it does appear to have "spread" to
      a number of signs that appear to have no such iconicity. There appears to be
      considerable variability in the use of the derivational markings, particularly in
      connected discourse, even for signs of the "open and shut" variety. Overall, the
      derivational process is apparently still closely linked to an iconic base, is
      incipient in the grammar of Auslan, and is thus best described as only partially
      grammaticalized.

PMID- 15451842
TI  - Construction of meaning in the authentic science writing of deaf students.
AB  - This study examines how students construct meaning through writing during
      authentic science activities. To determine how well students understood science
      concepts, we analyzed 228 writing samples from deaf students in grades 6 through
      11 as well as the explanatory and reflective comments of their teachers. The
      analyses indicate that certain process writing strategies were differentially
      useful in helping deaf students to construct meaning and in allowing teachers to
      evaluate the constructed meaning. Three instructional conditions and two teacher
      variables were found to play roles in determining the accuracy and adequacy of
      the writing: (1) the writing prompts the teachers used, (2) the focus for the
      writing, (3) follow-up to the initial writing activity, (4) the teacher's content
      knowledge, and (5) the teacher's ability to interpret student writing. The
      authors recommend future applications of writing-to-learn strategies and suggest
      directions for further research and changes in teacher education.

PMID- 15451843
TI  - College Students' Perceptions of the C-Print Speech-to-Text Transcription System.
AB  - C-Print is a real-time speech-to-text transcription system used as a support
      service with deaf students in mainstreamed classes. Questionnaires were
      administered to 36 college students in 32 courses in which the C-Print system was
      used in addition to interpreting and note taking. Twenty-two of these students
      were also interviewed. Questionnaire items included student ratings of lecture
      comprehension. Student ratings indicated good comprehension with C-Print, and the
      mean rating was significantly higher than that for understanding of the
      interpreter. Students also rated the hard copy printout provided by C-Print as
      helpful, and they reported that they used these notes more frequently than the
      handwritten notes from a paid student note taker. Interview results were
      consistent with those for the questionnaire. Questionnaire and interview
      responses regarding use of C-Print as the only support service indicated that
      this arrangement would be acceptable to many students, but not to others.
      Communication characteristics were related to responses to the questionnaire.
      Students who were relatively proficient in reading and writing English, and in
      speech-reading, responded more favorably to C-Print.

PMID- 15451844
TI  - Adopting Bilingual Education: An Australian School Community's Journey.
AB  - This article describes a case study of an Australian deaf facility and its
      changes in language policy. The study documents the process of change in a school
      community as the researcher worked collaboratively with teachers and parents to
      investigate the place of Auslan and bilingual pedagogy in deaf education.
      Teachers' dissatisfaction with educational outcomes and current practices
      propelled the discussion about language policy. Gaining the support of parents is
      a key feature of this study. Beliefs about language policy and practices are
      explored and the implications for change investigated. This is part of a larger
      study of deaf education and the politics of language practices (see Komesaroff,
      1998).

PMID- 15451845
TI  - Education of the deaf in nicaragua.
AB  - Nicaragua now ranks as the third poorest country in the Western Hemisphere
      (Interamerican Development Bank [IDB], 1995). Occasionally educational
      improvement has been a national priority (Arrien & Matus, 1989). Usually,
      however, education rests at the lower end of a long list of national needs. The
      history of education in Nicaragua is marked by low teacher salaries, deteriorated
      physical plants, and scarcities of teaching materials (Arnove, 1994). Deaf
      education has been no exception. Teachers have been expected to learn empirically
      what deafness is and how to teach deaf children, to teach pupils who have had
      little or no language exposure before entering school, and to manage with the
      barest physical resources, all the while receiving only meager compensation. This
      article places education of the deaf in Nicaragua in a historical perspective,
      reports the results of a teacher survey, and discusses national policies that, so
      far, have had only indirect effects, but are likely to gain importance in the
      future.

PMID- 15451846
TI  - Parents' Experience of Universal Neonatal Hearing Screening: A Critical Review of
      the Literature and Its Implications for the Implementation of New UNHS Programs.
AB  - This article presents a critical review of literature reporting the effects on
      parents of universal neonatal hearing screening (UNHS). It explores how parents
      experience the process and outcome of screening and in particular focuses on
      debates surrounding false positive identification, the evidence base for
      maternal/parental anxiety, consent, and family cultural/sociodemographic
      influences on the effective implementation of UNHS programs. These issues are
      then set within the context of events in the United Kingdom, where the Department
      of Health has recently initiated a program to pilot the introduction of universal
      neonatal hearing screening at 20 sites in England.

PMID- 15451847
TI  - Language facility and theory of mind development in deaf children.
AB  - Deaf children with signing parents, nonnative signing deaf children, children
      from a hearing impaired unit (HIU), and oral deaf children were tested on three
      first-order theory of mind (ToM) tasks--a subset was also given a second-order
      task (Perner & Wimmer, 1985). A British Sign Language (BSL) receptive language
      task (Herman, Holmes, & Woll, 1999) and four nonverbal executive function tasks
      were also administered. The new BSL task allowed, for the first time, the
      receptive language abilities of deaf children to be measured alongside ToM
      abilities. Hearing children acted as controls. These children were given the same
      tasks, except the British Picture Vocabulary Scale was substituted for the BSL
      task. Language ability correlated positively and significantly with ToM ability,
      and age was correlated with language ability for both the deaf and hearing
      children. Age, however, underpinned the relationship between ToM and language for
      deaf children with signing parents and hearing children but not for nonnative
      signing, HIU, or oral deaf children. Executive function performance in deaf
      children was not related to ToM ability. A subset of hearing children, matched on
      age and language standard scores with signing deaf children, passed significantly
      more ToM tasks than the deaf children did. The findings are discussed with
      respect to the hypotheses proposed by Peterson and Siegal (1995, 2000) and
      Courtin (2000).

PMID- 15451848
TI  - It's All a Matter of Timing: Sign Visibility and Sign Reference in Deaf and
      Hearing Mothers of 18-Month-Old Children.
AB  - The signed and spoken language produced by 14 mothers to their 18-month-old
      children during free play was analyzed. All the children had profound prelingual
      deafness. Seven of the mothers were profoundly deaf and fluent users of British
      Sign Language (BSL) or Auslan. The other seven were hearing and had enrolled in a
      signing program. Maternal signed utterances were classified according to whether
      they were made in the child's line of sight and whether they had a salient
      context; that is, they referred to an object or event at the child's current
      focus of attention. Spoken utterances were coded by word length. Comparisons
      between the two groups showed that both deaf and hearing mothers produced a
      majority of single-sign utterances (rather than utterances containing two or more
      signs). Deaf mothers also produced a majority of single-word spoken utterances,
      whereas the hearing mothers produced a significantly greater proportion of
      multiword utterances. As predicted, deaf mothers were more successful than
      hearing mothers in presenting signed utterances with a salient context that were
      visible to their children. Across the group as a whole, the total number of
      visible and salient signed utterances produced in 10 minutes was positively
      correlated with the total number of occasions on which mothers successfully
      redirected their child's attention or the child spontaneously turned to look at
      the mother. This suggests that deaf children who are visually attentive to their
      mothers receive a greater number of visible signed utterances with a salient
      context. I argue that this provides a more secure context for early language
      development.

PMID- 15451849
TI  - Peer relationships of children with cochlear implants.
AB  - Previous research on children with cochlear implants has focused mostly on their
      speech perception and production. With the growing numbers of children who use
      the implant, it is important to assess other aspects of these children's
      functioning. This article offers a qualitative and quantitative analysis of
      interviews with parents who described their children's communication skills and
      peer relationships before they had the implant and afterward. Results show that
      the implant has the potential to improve deaf children's relationships with
      hearing peers. Nonetheless, children with implants still face communication
      obstacles, which impede their social relationships with hearing peers. Results
      are discussed in light of the different points of view of various "stake holders"
      regarding cochlear implants in children.

PMID- 15451850
TI  - Deaf pupils' reasoning about scientific phenomena: school science as a framework
      for understanding or as fragments of factual knowledge.
AB  - Many studies have been conducted on hearing pupils' understanding of science.
      Findings from these studies have been used as grounds for planning instruction in
      school science. This article reports findings from an interview study of how deaf
      pupils in compulsory school reason about phenomena in a science context. The
      results reveal that there is variation in the extent to which pupils use
      scientific principles for reasoning about science phenomena. For some pupils,
      school science seems to have little to offer as a framework for reasoning. The
      results also generate questions about the need in school instruction of deaf and
      hard-of-hearing pupils to consider the specific teaching and learning situations
      in a deaf environment.

PMID- 15451851
TI  - Teaching strategies in inclusive classrooms with deaf students.
AB  - The purpose of this study was to investigate teacher speech and educational
      philosophies in inclusive classrooms with deaf and hearing students. Data were
      collected from language transcripts, classroom observations, and teacher
      interviews. Total speech output, Mean Length Utterance, proportion of questions
      to statements, and proportion of open to closed questions were calculated for
      each teacher. Teachers directed fewer utterances, on average, to deaf than to
      hearing students but showed different language patterns on the remaining
      measures. Inclusive philosophies focused on an individualized approach to
      teaching, attention to deaf culture, advocacy, smaller class sizes, and an
      openness to diversity in the classroom. The interpreters' role in the classroom
      included translating teacher speech, voicing student sign language, mediating
      communication between deaf students and their peers, and monitoring overall
      classroom behavior.

PMID- 15451852
TI  - Linguistic diversity in deaf defendants and due process rights.
AB  - Historically, ensuring the due process rights of deaf defendants has been a
      problematic issue in the criminal justice system (McAlister, 1994; Smith, 1994;
      Vernon & Coley, 1978; Vernon & Greenburg, 1996; Vernon & Miller, in press; Vernon
      & Raifman, 1997; Whalen, 1981; Wood, 1984). Inadequate communication can
      radically affect a deaf defendant's interactions in the courtroom. Pursuant to
      the concepts of fairness enshrined in the U.S. Constitution and the specific
      statutory language contained in federal and state laws, the courts must provide
      equal access for deaf defendants (Berko, 1992; Gallie & Smith, 2000; McCoy, 1992;
      Simon, 1994; Vernon & Raifman, 1997). It is the responsibility of the court to
      ensure that the appropriate accommodation is provided in the language most
      readily understood by the defendant.When adjudicating a deaf criminal defendant,
      courts must make certain that the defendant has equal access to various due
      process activities, such as assisting counsel in the development of a defense,
      deciding whether to testify, deciding which plea to enter, understanding the
      charges, understanding one's position as defendant, and comprehending the role of
      the defense and prosecuting attorneys, and judge (Berko, 1994; King, 1990; Simon,
      1994; Smith, 1994; Vernon & Coley, 1978; Vernon & Miller, in press; Vernon,
      Raifman, & Greenberg, 1996).However, complex linguistic issues that impinge on
      adjudicative competence are present in some deaf defendants (Vernon & Miller, in
      press; Vernon & Raifman, 1997). Adjudicative competence refers to an individual's
      ability to adequately comprehend and participate in legal proceedings and due
      process activities. When diverse language use is an issue, a deaf defendant's
      ability to participate in proceedings can be established by the court using the
      modern test of adjudicative competence (Dusky v. U.S., 1960). This test examines
      a defendant's state of mind at the time of trial rather than at the time of the
      offense in terms of these factors: a defendant's capacity to participate,
      reasonable understanding of the proceedings, and level of cognitive functioning,
      irrespective of any mental disorder. This article will outline linguistic
      barriers to due process for deaf defendants.

PMID- 15451853
TI  - Using research to improve literacy practice and practice to improve literacy
      research.
AB  - The disconnection between research and practice is not a new phenomenon, but as
      researchers and educators look toward the future of deaf education, it seems
      crucial to look back at the reasons behind this disconnection with the goal of
      creating a professional milieu in which we use research to improve literacy
      practice and practice to improve literacy research with deaf students. This
      article examines the issues underlying the relatively insignificant impact of
      research on literacy practice from the perspectives of the fields of literacy,
      special education, and deaf education.

PMID- 15451854
TI  - Theory of mind development in deaf children: a nonverbal test of false-belief
      understanding.
AB  - Our aim in this study was to investigate whether previous findings pointing to a
      delay in deaf children's theory of mind development are replicated when
      linguistic demands placed on the deaf child are minimized in a nonverbal version
      of standard false-belief tasks. Twenty-four prelingually deaf, orally trained
      children born of hearing parents were tested with both a verbal and a nonverbal
      version of a false-belief task. Neither the younger (range: 4 years 7 months-6
      years 5 months) nor the older (range: 6 years 9 months-11 years 11 months)
      children of the final sample of 21 children performed above chance in the verbal
      task. The nonverbal task significantly facilitated performance in children of all
      ages. Despite this facilitation, we observed a developmental delay: only the
      older group performed significantly above chance in the nonverbal false-belief
      task, even though the younger children were at the average age when hearing
      children normally pass standard false-belief tests. We discuss these findings in
      light of the hypothesis that language development and conversational competence
      are crucial to the acquisition of a theory of mind.

PMID- 15451855
TI  - Cognitive correlates of visual speech understanding in hearing-impaired
      individuals.
AB  - This study examined the extent to which different measures of speechreading
      performance correlated with particular cognitive abilities in a population of
      hearing-impaired people. Although the three speechreading tasks (isolated word
      identification, sentence comprehension, and text tracking) were highly
      intercorrelated, they tapped different cognitive skills. In this population,
      younger participants were better speechreaders, and, when age was taken into
      account, speech tracking correlated primarily with (written) lexical decision
      speed. In contrast, speechreading for sentence comprehension correlated most
      strongly with performance on a phonological processing task (written
      pseudohomophone detection) but also on a span measure that may have utilized
      visual, nonverbal memory for letters. We discuss the implications of this
      pattern.

PMID- 15451856
TI  - Effects of tactile training on visual speechreading: performance changes related
      to individual differences in cognitive skills.
AB  - We report on a follow-up study of the Ronnberg, Andersson, Lyxell, & Spens (1998)
      speech tracking training study. The purpose was to examine, initially and after
      training, the effects of different tactile aids on tasks of visual speechreading.
      We also examined cognitive prerequisites for initial baseline speechreading and
      posttraining speechreading performance. Compared with speechreading alone,
      tactile aids impaired sentence-based speechreading at first, although performance
      improved with training. No effects of vibrotactile aids or training were obtained
      for visual word-decoding. Initial baseline speechreading performance and
      posttraining performance correlated with cognitive skills, but the size of the
      correlations changed. The size of the correlations also varied with the different
      tactually mediated speechreading conditions.

PMID- 15451857
TI  - Interviewing deaf adults in postsecondary educational settings: stories,
      cultures, and life histories.
AB  - This article provides a brief examination of how Deaf adults describe their life
      histories as learners and as workers in the workforce. We show how these
      histories are intricately tied to the movements in and around the participants'
      social positions as Deaf persons in a hearing world. Three discursive positions
      are evident in the talk of these interviewees in relation to Deafness: as
      disability, as logistic complexity, and as community/culture. We also show how
      the life stories produced in the interviews entail variations on the theme of
      fragmentation: the losing, missing, and finding of viable life circumstances. In
      addition, we discuss how the interviewer-interviewee relationship comes to embody
      a hearing community's interests, recasting a Deaf interviewee's everyday life
      into a series of curiosities.

PMID- 15451858
TI  - Research and deaf education: moving ahead while glancing back.

PMID- 15451859
TI  - Application of demand-control theory to sign language interpreting: implications
      for stress and interpreter training.
AB  - The translation work of sign language interpreters involves much more than
      language. The characteristics and goings-on in the physical environment, the
      dynamics and interactions between the people who are present, and even the "inner
      noise" of the interpreter contribute to the accuracy, or lack thereof, of the
      resulting translation. The competent interpreter must understand and respond
      appropriately to the language and nonlanguage aspects of each interpreting
      assignment. We use the framework of demand-control theory (Karasek, 1979) to
      examine the complex occupation of sign language interpreting. Demand-control
      theory is a job analysis method useful in studies of occupational stress and
      reduction of stress-related illness, injury, and burnout. We describe sources of
      demand in the interpreting profession, including demands that arise from factors
      other than those associated with languages (linguistic demands). These include
      environmental, interpersonal, and intrapersonal demands. Karasek's concept of
      control, or decision latitude, is also explored in relation to the interpreting
      profession. We discuss the prevalence of cumulative trauma disorders (CTD),
      turnover, and burnout in the interpreting profession in light of demand-control
      theory and data from interpreter surveys, including a new survey study described
      herein. We conclude that nonlinguistic demand factors in particular and perceived
      restrictions in decision latitude likely contribute to stress, CTD, burnout, and
      the resulting shortage of sign language interpreters. We make suggestions for
      improvements in interpreter education and professional development, including the
      institution of an advanced, supervised professional training period, modeled
      after internships common in other high demand professional occupations.

PMID- 15451860
TI  - Structures underpinning pretend play and word production in young hearing
      children and children with hearing loss.
AB  - Relationships between pretend play and word production were investigated in 10
      hearing (H) and 10 toddlers with hearing loss (D) who attended an auditory/oral
      early intervention program. All children were videotaped interacting in free play
      with their hearing primary caregiver at 28, 29, and 30 months of age. Group
      comparisons were made for the scores for highest and mean levels of pretend play
      and for the underlying structures of decontextualization, decentration,
      sequencing, and planning. Relationships with word production were then explored
      for the two groups separately. Results showed significantly higher levels of
      pretend play for all dimensions for the hearing children and an association
      between level of pretend play and word production for the children with hearing
      loss. Associations between word production and sequencing and planning were found
      for both groups of children. Word production was associated with
      decontextualization for the hearing children and with decentration for the
      children with hearing loss. We discuss theoretical implications of the findings
      together with implications for intervention with toddlers who have hearing loss.

PMID- 15451861
TI  - Effects of articulation training on the production of trained and untrained
      phonemes in conversations and formal tests.
AB  - The aim of this study was to investigate the effectiveness of articulation
      training for specific phonemes on the production of phonemes in conversational
      language samples, the 108 Single Word Articulation Test (Paatsch, 1997), and the
      Phonetic Level Evaluation (Ling, 1976). Speech production skills of 12 hearing
      impaired children were assessed using these evaluation tools pre- and
      posttraining. A total of six phonemes were selected for each child to be trained
      during 15-to 20-minute daily sessions throughout an 8-week speech production
      program. Three phonemes, with a particularly high error rate, were trained at a
      phonetic level (category 1) while three phonemes, with an intermediate error rate
      of 40% to 70%, were trained at a phonological level (category 2). Results showed
      improvements in the percentage of correctly articulated category 1 phonemes and
      category 2 phonemes. The improvements for category 2 phonemes were larger than
      for category 1 phonemes for all test materials. It may be that phonological level
      training is more effective than phonetic level training or that phonemes with an
      intermediate error rate are easier to train than phonemes with a high error rate.
      Untrained vowels and consonants also improved slightly after training.
      Phonological process analysis showed that many of the errors apparent in the
      trained phonemes also had occurred in the untrained phonemes. This may have
      resulted in the generalization and carryover of taught speech skills into other
      aspects of the child's spoken language.

PMID- 15451862
TI  - Television literacy: comprehension of program content using closed captions for
      the deaf.
AB  - Recent legislation has made captioned television programs common technology;
      consequently, televised programs have become more accessible to a broader public.
      In the United States, television captions are generally in written English, yet
      the English-literacy rates among people who are deaf are low compared to hearing
      peers. This research tests the accessibility of television by assessing deaf and
      hearing students' comprehension of captions with and without visuals/video based
      on their ability to respond correctly to questions about the script and central
      details. Results indicate that reading grade level is highly correlated with
      caption comprehension test scores. Across caption conditions, comprehension test
      scores of students who are deaf were consistently below the scores of hearing
      students. The captioned video provided significantly better comprehension of the
      script for students who are deaf, suggesting that visual stimuli provide
      essential information for viewers who are deaf, which improves comprehension of
      televised script.

PMID- 15451863
TI  - Self-concept of deaf secondary school students in different educational settings.
AB  - The purpose of this study was to examine the effects of different educational
      settings on the self-concept of deaf secondary school students. The Self
      Description Questionnaire-1 (Marsh, 1986), a multidimensional measure, was
      linguistically modified and sign language videos were produced for those using
      sign communication. In the main study, the participants were deaf secondary
      students from three school settings: segregated (institutional), congregated (a
      new facility housing the previously segregated school for the deaf and a hearing
      secondary school), resource programs (in mainstream schools, providing both
      special class instruction and opportunities for integration). Examining
      dimensions of self-concept, the results identified academic advantages in
      attending resource programs and social advantages in attending segregated
      settings. Overall, deaf students who were integrated with hearing students had
      better self-perceptions of reading ability than those in special classes.
      Additional analyses with subsamples of deaf students found no significant
      differences between those using spoken and sign communication in any dimension of
      self-concept.

PMID- 15451864
TI  - "Does god have a cochlear implant?".
AB  - This article describes psychological and ethical considerations when providing
      family therapy for parents considering cochlear implantation for their deaf/hard
      of-hearing child. Family dynamics, multilevel criteria of informed consent,
      therapist bias, intervention strategies are illustrated. The clinical vignette of
      8-year-old Tommy and his family is largely factual, with enough changes to
      disguise the participants' identities. I took more creative liberties narrating
      my daydream to best illustrate the relevant impacts of the pathological and
      culturally affirmative models.

PMID- 15451865
TI  - Higher education for deaf students: research priorities in the new millennium.
AB  - A review of research on deaf students in higher education reveals a significant
      body of knowledge about the barriers these students face in gaining access to
      information in the classroom. Much less is known about the potential solutions to
      these problems. In addition, there is a dearth of research on the effectiveness
      of such support services as interpreting, note taking, real-time captioning, and
      tutoring, particularly with regard to their impact on academic achievement. This
      article summarizes relevant research and suggests directions for educational
      researchers interested in enhancing academic success and the retention of deaf
      students in higher education programs.

PMID- 15451866
TI  - University interpreting: linguistic issues for consideration.
AB  - This study describes Auslan/English interpreters' use of translation style when
      interpreting for a university lecture. Some interpreters switched translation
      style, between free and literal methods of interpretation, as a linguistic
      strategy for dealing with the sociolinguistic influences of the discourse
      environment. In particular, attention was paid to the interpreters' educational
      background (and therefore their familiarity with academic discourse), the
      linguistic features and lexical density of the text, and their influences on the
      interpretation. The key finding of the study was that Auslan/English interpreters
      predominantly used a free or literal interpretation approach, but switched
      between translation styles at particular points of the text, leading to the
      suggestion of the concept of "translational contact." The findings of this study
      are not only significant in Australia but can also benefit interpreters and
      interpreter educators internationally.

PMID- 15451867
TI  - The Characteristics and Extent of Participation of Deaf and Hard-of-Hearing
      Students in Regular Classes in Australian Schools.
AB  - A national randomly selected survey of a sample of deaf and hard-of-hearing
      students included in regular classes from kindergarten to high school in
      Australian preschools and schools was conducted via a questionnaire to itinerant
      teachers working with such students. This article reports the analysis of a
      questionnaire that surveyed the demographic characteristics of such students and
      a set of characteristics of their behavior in their placement in terms of
      "participation" in aspects of regular class activities. These aspects were level
      of integration, academic participation, level of independence, and social
      participation. Data are reported and analyzed in terms of the above demographic
      and participatory characteristics of the students. We consider comparisons with
      comparable reports from the United States and Great Britain and discuss
      implications for deaf and hard-of-hearing students included in regular classes.

PMID- 15451868
TI  - Communication mode and the processing of printed words: evidence from readers
      with prelingually acquired deafness.
AB  - The aim of this study was to elucidate how the primary communication background
      of prelingual deafened readers affects the way they mediate the recognition of
      written words. A computer-controlled research paradigm (a semantic decision task)
      asking for the categorization of familiar Hebrew nouns was used to investigate
      the participants' sensibility to phonological and orthographic manipulations in
      the target stimuli. Two groups of readers with hearing impairments and a hearing
      control group participated in the study. Twenty-seven of the participants with
      deafness (mean grade 6.9) were raised by hearing parents advocating a strict oral
      approach at home and at school. For an additional 22 students who were deaf (mean
      grade 6.9), the majority of them children of deaf parents, Israeli Sign Language
      was the preferred means of communication. The mean grade of the 39 participants
      in the hearing control group was 6.5. Findings indicate that both the hearing
      participants and the participants with prelingual deafness who were trained to
      communicate orally recoded visually presented target words phonologically. No
      such evidence was found for participants with deafness who were native signers.
      Although participants from signing backgrounds seemed to generate nonphonological
      representations of written words, there was no evidence that for them, the
      absence of recoding to phonology detrimentally affected on their ability to
      process such representations flexibly. In all, findings suggest a causal link
      between an individual's processing strategy for some written words and the modal
      nature of his or her primary language.

PMID- 15451869
TI  - Parenting stress and social support in hearing mothers of deaf and hearing
      children: a longitudinal study.
AB  - This longitudinal study investigated the impact of child deafness on mothers'
      stress, size of social networks, and satisfaction with social support. Twenty
      three hearing mothers of deaf children and 23 hearing mothers of hearing children
      completed a series of self-report questionnaires when their children were 22
      months, 3, and 4 years old. When children were 22 months, more mothers of deaf
      children reported pessimism about their children's achieving self-sufficiency and
      concerns about their children's communication abilities than did mothers of
      hearing children. When their children were 3 and 4 years old, mothers of deaf and
      hearing children did not differ in their reports of general parenting stress, as
      measured by the Parenting Stress Index (PSI). Likewise, mothers' ratings of
      satisfaction with social support were not affected by child deafness, nor did
      they change developmentally. Mothers of deaf and hearing children did differ in
      the types of support networks utilized. Mothers of deaf 22-month-olds reported
      significantly larger professional support networks, while mothers of hearing
      children reported significantly larger general support networks across all child
      ages. Mothers' feelings of stress and satisfaction with social support were very
      stable across the 2 years examined. The results suggest that most mothers of deaf
      children do not feel a high level of general parenting stress or dissatisfaction
      with their lives and support networks. However, mothers of deaf children are
      likely to feel stress in areas specific to deafness. In addition, because
      parenting stress was highly stable, special efforts should be made to intervene
      when mothers of deaf children are expressing high levels of stress.

PMID- 15451870
TI  - Images of teacher, students, and the classroom held by preservice and in-service
      educators of students who are deaf or hard of hearing.
AB  - A sample of 163 preservice and in-service teachers of deaf and hard-of-hearing
      students was surveyed on perceptions of the roles of teacher, students, and the
      classroom. The participants' perceptions were examined utilizing the Survey of
      Practical Knowledge (SPK) designed and developed by the researcher for the study.
      The SPK asked the participants to respond to different "images" of teachers,
      students, and classrooms. Through factor analysis, the following images were
      generated: the teacher as artisan, the teacher as custodian, the student as
      subordinate, the student as peer, the classroom as arena, and the classroom as
      refuge. Beginning education students, graduating education students, novice
      teachers, and experienced teachers were assessed on their endorsement of those
      images. Beginning education students tended to view students more as peers than
      members of the other three groups. In-service teachers were more consistent and
      flexible in their images than preservice teachers were. Deaf and hard-of-hearing
      teachers viewed students more as subordinates than did hearing teachers. The
      dominant view among the study participants conceptualized the teacher as artisan,
      the students as subordinates, and the classroom as a refuge.

PMID- 15451871
TI  - Perspectives on inclusion.

PMID- 15451872
TI  - Least restrictive environment and the courts.
AB  - This article provides a description and an analysis of how the U.S. federal
      courts have interpreted the least restrictive environment (LRE) clause in the
      Individuals with Disabilities Education Act (IDEA) since passage of the act by
      Congress in 1975. It begins with a brief highlighting of critical events in the
      evolution of the LRE concept in the political environment, particularly the
      impact of the clause on the educational placement of deaf children. The central
      roles within the IDEA of due process and parental involvement in educational
      decision making are then described. The article then charts the early (i.e.,
      during the eighties and early nineties) evolution of judicial interpretation of
      LRE, before moving on to a review of cases involving the educational placement of
      deaf children where LRE has been a central issue. The first set of cases reviewed
      was all decided at the federal appeals court level, the second set at federal
      district court level. The article concludes with a comment regarding the
      prospects for a more balanced approach to educational placement for deaf
      youngsters.

PMID- 15451873
TI  - Social processes and outcomes of in-school contact between deaf and hearing
      peers.
AB  - Studies of social processes and outcomes of the placement of deaf students with
      hearing peers cannot be easily summarized, but can be grouped into a least four
      major categories of focus: social skills, interaction and participation,
      sociometric status and acceptance, and affective functioning. We review 33
      studies available since 1980 in which a mainstreamed or included deaf sample was
      compared to another group. Studies indicated (1) that hearing students were more
      socially mature than deaf students in public schools, (2) that deaf students
      interacted with deaf classmates more than hearing ones, (3) that deaf students
      were somewhat accepted by their hearing classmates, and (4) that self-esteem was
      not related to extent of mainstreaming. There was a tendency for studies to use
      observational methods with very young children, teacher evaluations with middle
      school children, and questionnaires with older children. Three major areas of
      methodology limit general conclusions: samples, measurements of variables, and
      experimental manipulations. The reviewed studies provide a basis for
      understanding the social processes and outcomes in these placement situations;
      however, it is not possible to make broad generalizations about effects of
      placement.

PMID- 15451874
TI  - Developing Membership in the Education of Deaf and Hard-of-Hearing Students in
      Inclusive Settings.
AB  - This article discusses the importance of membership in the inclusive education of
      deaf/hard-of-hearing (D/HH) students. Membership refers to being an integral part
      of the classroom and school communities. Membership is a key philosophical
      concept in inclusion that may influence how classroom teachers and teachers of
      D/HH students share their expertise and how they work with students and each
      other. Membership can be contrasted with "visitorship." When programs treat D/HH
      students as visitors, these students face greater barriers to obtaining a quality
      education in classes with hearing students. A social constructivist perspective
      of learning and teaching that requires students in the classroom to interact with
      one another and the teacher may best promote learning and is consistent with a
      focus on membership. We suggest that inclusion is possible, but to sustain
      students as full members of their classes and school, programs must go beyond
      placement and communication access issues. To facilitate membership, inclusive
      programs must carefully address teacher attitudes, teacher roles and
      relationships, student knowledge and curriculum, structural barriers,
      extracurricular activities, community relationships, and parental support.

PMID- 15451875
TI  - From concepts to practice in deaf education: a United kingdom perspective on
      inclusion.
AB  - This article considers the different ways that inclusion is conceived in the
      United Kingdom by government, teachers, and academics. I contend that a concept
      of inclusion based primarily on the notion of students with special educational
      needs being in mainstream schools is unhelpful to educators of deaf children and
      that a broader concept is needed. A working definition of inclusion is presented
      based on a system of values. I suggest "indicators of inclusion for deaf
      students" and illustrate with examples of practice. Some basic information on the
      education of deaf children in the United Kingdom is included.

PMID- 15451876
TI  - Inclusion of students who are deaf or hard of hearing in government schools in
      new South wales, australia: development and implementation of a policy.
AB  - The inclusion of students who are deaf or hard of hearing in Department of
      Education and Training (government) schools in the state of New South Wales,
      Australia, is supported through a policy known as the Special Education Policy
      (NSW Department of School Education, 1993). The policy is operational for all
      students with disabilities, learning difficulties, or behavior disorders,
      regardless of their educational provision. This article focuses on how the policy
      and continuum of services have developed and the attitudes of stakeholders toward
      both policy and practice. The article begins by framing the policy in terms of
      legal mandates and then gives an overview of current educational provisions,
      followed by a discussion of attitudes toward inclusion as held by stakeholders in
      New South Wales government schools. The article concludes by attempting to assess
      the potential effects of both policy and practice on students who are deaf or
      hard of hearing.

PMID- 15451877
TI  - The argument for a constitutional right to communication and language.
AB  - The need for and right to communication and language is fundamental to the human
      condition. Without communication, an individual cannot become an effective and
      productive adult or an informed citizen in our democracy. The importance of
      communication and language for deaf and hard-of-hearing children is so basic as
      to be beyond debate. Given the historic difficulties deaf and hard-of-hearing
      children face, their compromised communication and language skills and the
      educational, social, cognitive, and psychological consequences, this note
      contends that a constitutional right to communication is both necessary and
      legally sound. The right to assemble and to vote, the right to equal protection
      under the law must be extended to the right of deaf and hard-of-hearing children
      to full communication development and access. If the Constitution venerates the
      right to speech, the right to communication and language is of equal or greater
      value.

PMID- 15451878
TI  - The MacArthur Communicative Development Inventory: Normative Data for American
      Sign Language.
AB  - To This is a 1 test per thousand learn more about normal language development in
      deaf children, we have developed the MacArthur Communicative Development
      Inventory for American Sign Language (ASL-CDI), a parent report that measures
      early sign production. The ASL-CDI is an inventory of sign glosses organized into
      semantic categories targeted to assess sign language skills in children ages 8 to
      36 months. The ASL-CDI uses a recognition format in which parents check off signs
      that their child produces. The form has demonstrated excellent reliability and
      validity. To date, normative data have been collected from 69 deaf children with
      deaf parents who are learning sign language as a first language. We discuss the
      development of the ASl-CDI and preliminary cross-sectional and longitudinal
      findings from this early data collection with particular focus on parallels with
      spoken language acquisition. We also discuss the acquisition of first signs,
      negation, wh-questions, and fingerspelling with developmental patterns provided
      based on age, as well as vocabulary size.

PMID- 15451879
TI  - Story problems in the deaf education classroom: frequency and mode of
      presentation.
AB  - Over the past decade, curricular reform in mathematics education has emphasized
      the use of problem solving at all levels of instruction for all students, but
      adaptations for students with unique needs have not been specified. This study
      investigated the nature of problem solving in deaf education, focusing in
      particular on the use of story problems in the primary-level curriculum.
      Approximately 90% of the K-3 teachers from five schools for the deaf were asked
      with what frequency and in which communication mode they presented story problems
      to their students. Most teachers reported presenting story problems 1-3 times per
      week, and presentation method tended to reflect school communication philosophy.
      We found trends in story problem presentation in accordance with the mathematics
      grade level taught. We discuss implications for curricular reform and teacher
      education.

PMID- 15451880
TI  - An intervention program for promoting deaf pupils' achievement in mathematics.
AB  - Our past research identified two aspects of deaf children's functioning that
      places them at risk for underachievement in mathematics. The first is their
      reduced opportunities for incidental learning, and the second is their difficulty
      in making inferences involving time sequences. This article examines the
      effectiveness of an intervention program to promote deaf children's numeracy that
      was designed to deal with these two factors. The design involved a comparison of
      23 deaf pupils participating in the project with a baseline group formed by 65
      deaf pupils attending the same schools in the previous year. The project pupils
      were tested before and after the intervention on the NFER-Nelson Age Appropriate
      Mathematics Achievement Test. The intervention was delivered by the teachers
      during the time normally scheduled for mathematics lessons. The project pupils
      did not differ from the baseline group at pretest but performed significantly
      better at posttest. They also performed at posttest better than expected on the
      basis of their pretest scores, according to norms provided by the NFER-Nelson Age
      Appropriate Mathematics Test for assessing the progress of hearing pupils. We
      conclude that the program was effective in promoting deaf pupils' achievement in
      numeracy.

PMID- 15451881
TI  - Hard-of-Hearing Adolescents and Identity Construction: Influences of School
      Experiences, Peers, and Teachers.
AB  - This qualitative study explored the identity construction of seven adolescents
      who attended special classes for hard-of-hearing (HH) students for part or all of
      their elementary school years. Results of open-ended group interviews and written
      questionnaires indicated that the students strongly identified as HH people.
      School experiences and interactions with teachers and HH peers appeared to be
      major influences on this choice. The findings support the position that a HH
      identity may exist separate from the culturally Deaf identity. The findings also
      suggest that HH students need to connect with other HH individuals whether or not
      they assimilate into the hearing world or decide to participate in both the
      hearing and Deaf worlds.

PMID- 15451882
TI  - The benefit of assessment-based language and reading instruction: perspectives
      from a case study.
AB  - We present a case study of the language and literacy development of a deaf child,
      Marcy, from preschool through sixth grade. The purpose of the project was to
      examine the connection between language and reading and to provide insight into
      the relationships between them. To compile the case study, we analyzed data from
      nine years of follow-up, including listening, speech articulation, semantic,
      syntactic, reading, and writing information drawn from a number of informal and
      formal assessments. Annual evaluation of language and literacy skills was used to
      select educational placements, as well as instructional methods, strategies, and
      materials. Given that Marcy began school at 4 years of age, mute and without
      expressive language of any form (oral or sign), it may at first appear remarkable
      that she read narrative and expository text as did her hearing peers by sixth
      grade, because a substantial body of research shows that most deaf students read
      at the fourth-grade level by high school graduation (review by Paul, 1998).
      However, those responsible for Marcy's education prevented reading failure by
      carefully planning, instituting, and monitoring elements of language and literacy
      instruction. We present Marcy's progress and instruction by grade level and
      discuss it within the framework of phases/stages of reading development. We hope
      that the resulting case study may serve as an example of the language-reading
      connection, an awareness important not only for the literacy instruction of deaf
      and language-challenged children but for hearing students as well.

PMID- 15451883
TI  - Predictors of parental stress in mothers of young children with hearing loss.
AB  - This study examined parental stress in 184 hearing mothers of young children who
      are deaf or hard of hearing. Stress levels were measured in three domains using
      the short-form of the Parental Stress Index (PSI; Abidin, 1995). Mothers in this
      study demonstrated significantly less parental distress on the PSI than a
      normative, hearing group, although this difference was quite small. Differences
      between the hearing and hearing loss samples did not reach conventional levels of
      significance for the Dysfunctional Parent-Child Interactions or the Difficult
      Child subscales. An examination of potential predictors of maternal stress
      revealed that mothers who perceived their daily hassles as more intense also
      obtained higher stress ratings on all three subscales. Additional predictors of
      parental distress were frequency of hassles, social support, and annual family
      income. Increased stress on the Dysfunctional Parent-Child Interaction subscale
      was predicted by children who had disabilities in addition to hearing loss, more
      delayed language relative to their chronological age, and less severe degrees of
      hearing loss. No additional, significant predictors were obtained for the
      Difficult Child subscale. When all measured variables were controlled for,
      characteristics that did not predict maternal stress on any of the three
      subscales included the child's gender, ethnicity, age of identification, mode of
      communication used, maternal education, and months between age of identification
      and child age at the time of observation.

PMID- 15451884
TI  - Issues in development of the test battery for Australian sign language morphology
      and syntax.
AB  - In this article, we outline the initial stages in development of an assessment
      instrument for Australian Sign Language and explore issues involved in the
      development of such a test. We first briefly describe the instruments currently
      available for assessing grammatical skills in Australian Sign Language and
      discuss the need for a more objective measure. We then describe our adaptation of
      an existing American Sign Language test, the Test Battery for American Sign
      Language Morphology and Syntax. Finally, this article presents some of the data
      collected from a group of deaf native signers. These data are used to demonstrate
      the range of variability in key grammatical features of Australian Sign Language
      and to raise methodological issues associated with signed language test design.

PMID- 15451885
TI  - Age and language skills of deaf children in relation to theory of mind
      development.
AB  - Using four traditional false-belief tasks, I investigated deaf children's age and
      expressive language skills in relation to their theory of mind development. The
      children's parents who signed reported on their own knowledge of a mental sign
      vocabulary. The results indicate age of the child to be strongly related to
      theory of mind development. Deaf children demonstrated an ability to pass the
      theory of mind assessment battery between the ages of 7 and 8 years, on average.
      In comparison, hearing children have consistently demonstrated the ability to
      perform such tasks between the ages of 4 and 5 years. Therefore, the results
      indicate deaf children are delayed by approximately 3 years in this cognitive
      developmental milestone. Expressive language skills of the children and sign
      language skills of the parents who signed were not found to be significantly
      related to the children's theory of mind development.

PMID- 15451886
TI  - Norwegian deaf teachers' reflections on their science education: implications for
      instruction.
AB  - In this study, undertaken in an attempt to expand our understanding of science
      learning by deaf students, five teachers are interviewed about their views, based
      on their own experiences as Deaf students. They are all my former students and
      were among the first to successfully complete the upper secondary school with a
      university entrance certificate from a Norwegian school for deaf students.
      Physics was their major subject. These teachers see the systematic work in class
      discussions, especially on the concepts of physics, as a major contributor to
      their success, and they try to use similar methods in their own teaching. They
      believe that a thorough discussion of a topic using sign language prior to the
      reading of the textbook is crucial.

PMID- 15451887
TI  - A Review of Issues in Deaf Education Under Nigeria's 6-3-3-4 Education System.
AB  - This article examines issues affecting the education of deaf people under
      Nigeria's 6-3-3-4 system of education. The system was introduced in 1976 and
      serves all categories of learners in Nigeria, irrespective of disability. The
      broad aim of education under the system is to provide all Nigerian learners a
      wide variety of educational and vocational opportunities to ensure the optimum
      development of their potential. Evidence indicates that the implementation of the
      6-3-3-4 system in Nigerian schools, including schools for the deaf, remains
      unsatisfactory. A plethora of problems running the gamut from inadequate
      personnel training programs, lack of facilities, failure of inclusion programs,
      to limited vocational preparation opportunities, inadequate funding of services,
      and absence of a legislation supporting the implementation of the 6-3-3-4 system
      are identified as the major factors militating against the effective
      implementation of the system in Nigerian schools, including schools for the deaf.
      The implications for improvements in these areas to achieve a more meaningful
      implementation of the 6-3-3-4 system are discussed.

PMID- 15451888
TI  - Differentiation of human melanoma cells induced by cyanidin-3-O-beta
      glucopyranoside.
AB  - Great attention has been recently given to a flavonoid of the anthocyanin class,
      cyanidin-3-O-beta-glucopyranoside (C-3-G), which is widely spread throughout the
      plant kingdom, and is present in both fruits and vegetables of human diets. In
      this study, we investigated the effect of C-3-G on proliferation and
      differentiation of human melanoma cells. Both morphological and functional
      parameters were evaluated, using electron and confocal microscopy,
      cytofluorometric analysis, HPLC assay, Western blot analysis, and enzymatic
      assay, as appropriate. A treatment with a single dose of C-3-G decreased cell
      proliferation without affecting cell viability and without inducing apoptosis or
      necrosis. The mitotic index and cell percentage in S phase were significantly
      lower in C-3-G treated cells compared with untreated control. C-3-G treatment
      induced, in a dose- and time-dependent manner, melanoma cell differentiation
      characterized by a strong increase in dendrite outgrowth accompanied with a
      remodeling of the microtubular network, a dramatic increase of focal adhesion and
      an increased expression of "brain specific" cytoskeletal components such as NF
      160 and NF-200 neurofilament proteins. C-3-G treatment also induced increase of
      cAMP levels and up-regulation of tyrosinase expression and activity resulting in
      an enhanced melanin synthesis and melanosome maturation. Up-regulation of the
      melanoma differentiation antigen Melan-A/MART-1 in treated cells respect to the
      untreated control was also recorded. Data obtained provide evidence that a single
      treatment with C-3-G is able to revert the human melanoma cells from the
      proliferating to the differentiated state. We conclude that C-3-G is a very
      promising molecule to include in the strategies for treatment of melanoma; also
      because of its nutritional relevance.

PMID- 15451889
TI  - Acute physiological response of mammalian central neurons to axotomy: ionic
      regulation and electrical activity.
AB  - The transection of the axon of central neurons has dramatic consequences on the
      damaged cells and nerves. Injury activates molecular programs leading to a
      complex repertoire of responses that, depending on the cellular context, include
      activation of sprouting, axonal degeneration, and cell death. Although the
      cellular mechanisms started at the time of lesion are likely to shape the changes
      affecting injured cells, the acute physiological reaction to trauma of mammalian
      central neurons is not completely understood yet. To characterize the physiology
      of the acute response to axonal transection, we have developed a model of in
      vitro axotomy of neurons cultured from the rodent cortex. Imaging showed that
      axotomy caused an increase of calcium in the soma and axon. Propagation of the
      response to the soma required the activation of voltage-dependent sodium
      channels, since it was blocked by tetrodotoxin. The electrophysiological response
      to axotomy was recorded in patched neurons kept in the current clamp
      configuration: injury was followed by vigorous spiking activity that caused a
      sodium load and the activation of transient calcium currents that were opened by
      each action potential. The decrease of the electrochemical gradient of sodium
      caused inversion of the Na-Ca exchanger that provided an additional mean of entry
      for calcium. Finally, we determined that inhibition of the physiological response
      to axotomy hindered the regeneration of a new neurite. These data provide
      elements of the framework required to link the axotomy itself to the downstream
      molecular machinery that contributes to the determination of the long-term fate
      of injured neurons and axons.

PMID- 15451890
TI  - The impact of a decade of changing treatment on rates of severe hypoglycemia in a
      population-based cohort of children with type 1 diabetes.
AB  - OBJECTIVE: To determine the impact of changes to treatment on the incidence of
      severe hypoglycemia and its risk factors in a large population-based cohort of
      children with type 1 diabetes. RESEARCH DESIGN AND METHODS: The cohort consisted
      of 1,335 children (age at entry 9.5 +/- 4.3 years [mean +/- SD], range 0-18),
      yielding 6,928 patient-years of data. The mean follow-up period was 4.7 +/- 3.1
      years (range 0-10.7). Prospective assessment of severe hypoglycemia (an event
      leading to loss of consciousness or seizure) and associated clinical factors and
      outcomes was made between 1992 and 2002. Patients were reviewed every 3 months.
      Data were analyzed using the negative binomial regression model. RESULTS: A total
      of 944 severe events were recorded. The incidence of severe hypoglycemia
      increased significantly by 29% per year for the first 5 years but appeared to
      plateau over the last 5 years. The overall average HbA1c significantly decreased
      (by 0.2% per year) over the whole follow-up period. An increased risk of severe
      hypoglycemia was associated with lower HbA1c, younger age, higher insulin dose,
      male sex, and lower parental socioeconomic status. Of insulin therapies, only
      pump treatment was associated with reduced rates of severe hypoglycemia.
      CONCLUSIONS: Severe hypoglycemia remains a major problem for children and
      adolescents with type 1 diabetes. Recent approaches to therapy may be allowing a
      degree of improved control without the expected increased risk of severe
      hypoglycemia but further monitoring will be important.

PMID- 15451891
TI  - A controlled trial of population management: diabetes mellitus: putting evidence
      into practice (DM-PEP).
AB  - OBJECTIVE: Population-level strategies to organize and deliver care may improve
      diabetes management. We conducted a multiclinic controlled trial of population
      management in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: We
      created diabetic patient registries (n = 3,079) for four primary care clinics
      within a single academic health center. In the intervention clinic (n = 898), a
      nurse practitioner used novel clinical software (PopMan) to identify patients on
      a weekly basis with outlying values for visit and testing intervals and last
      measured levels of HbA1c, LDL cholesterol, and blood pressure. For these
      patients, the nurse practitioner e-mailed a concise patient-specific summary of
      evidence-based management suggestions directly to primary care providers (PCPs).
      Population changes in risk factor testing, medication prescription, and risk
      factor levels from baseline (1 January 2000 to 31 August 2001) to follow-up (1
      December 2001 to 31 July 2003) were compared with the three usual-care control
      clinics (n = 2,181). RESULTS: Patients had a mean age of 65 years, were mostly
      white (81%), and the majority were insured by Medicare/Medicaid (62%). From
      baseline to follow-up, the increase in proportion of patients tested for HbA1c (P
      = 0.004) and LDL cholesterol (P < 0.001) was greater in the intervention than
      control sites. Improvements in diabetes-related medication prescription and
      levels of HbA1c, LDL cholesterol, and blood pressure in the intervention clinic
      were balanced by similar improvements in the control sites. CONCLUSIONS:
      Population-level clinical registries combined with summarized recommendations to
      PCPs had a modest effect on management. The intervention was limited by good
      overall quality of care at baseline and temporal improvements in all control
      clinics. It is unknown whether this intervention would have had greater impact in
      clinical settings with lower overall quality. Further research into more
      effective methods of translating population registry information into action is
      required.

PMID- 15451892
TI  - A population-based study of diabetes and its characteristics during the fasting
      month of Ramadan in 13 countries: results of the epidemiology of diabetes and
      Ramadan 1422/2001 (EPIDIAR) study.
AB  - OBJECTIVE: The aim of this study was to assess the characteristics and care of
      patients with diabetes in countries with a sizable Muslim population and to study
      diabetes features during Ramadan and the effect of fasting. RESEARCH DESIGN AND
      METHODS: This was a population-based, retrospective, transversal survey conducted
      in 13 countries. A total of 12,914 patients with diabetes were recruited using a
      stratified sampling method, and 12,243 were considered for the analysis. RESULTS:
      Investigators recruited 1,070 (8.7%) patients with type 1 diabetes and 11,173
      (91.3%) patients with type 2 diabetes. During Ramadan, 42.8% of patients with
      type 1 diabetes and 78.7% with type 2 diabetes fasted for at least 15 days. Less
      than 50% of the whole population changed their treatment dose (approximately one
      fourth of patients treated with oral antidiabetic drugs [OADs] and one-third of
      patients using insulin). Severe hypoglycemic episodes were significantly more
      frequent during Ramadan compared with other months (type 1 diabetes, 0.14 vs.
      0.03 episode/month, P = 0.0174; type 2 diabetes, 0.03 vs. 0.004 episode/month, P
      < 0.0001). Severe hypoglycemia was more frequent in subjects who changed their
      dose of OADs or insulin or modified their level of physical activity.
      CONCLUSIONS: The large proportion of both type 1 and type 2 diabetic subjects who
      fast during Ramadan represent a challenge to their physicians. There is a need to
      provide more intensive education before fasting, to disseminate guidelines, and
      to propose further studies assessing the impact of fasting on morbidity and
      mortality.

PMID- 15451893
TI  - Organizational factors affecting the adoption of diabetes care management
      processes in physician organizations.
AB  - OBJECTIVE: To describe the extent of adoption of diabetes care management
      processes in physician organizations in the U.S. and to investigate the
      organizational factors that affect the adoption of diabetes care management
      processes. RESEARCH DESIGN AND METHODS: Data are derived from the National Survey
      of Physician Organizations and the Management of Chronic Illness, conducted in
      2000-2001. A total of 1,104 of the 1,590 physician organizations identified
      responded to the survey. The extent of adoption of four diabetes care management
      processes is measured by an index consisting of the organization's use of
      diabetic patient registries, clinical practice guidelines, case management, and
      physician feedback. The ordinary least-squares model is used to determine the
      association of organizational characteristics with the adoption of diabetes care
      management processes in physician organizations. A logistic regression model is
      used to determine the association of organizational characteristics with the
      adoption of individual diabetes care management processes. RESULTS: Of the 987
      physician organizations studied that treat patients with diabetes, 48% either do
      not use any or use only one of the four diabetes care management processes. A
      total of 20% use two care management processes, and 32% use three or four
      processes. External incentives to improve quality, computerized clinical
      information systems, and ownership by hospitals or health maintenance
      organizations are strongly associated with the diabetes care management index and
      the adoption of individual diabetes care management processes. CONCLUSIONS:
      Policies to encourage external incentives to improve quality and to facilitate
      the adoption of computerized clinical information technology may promote greater
      use of diabetes care management processes.

PMID- 15451894
TI  - Differences in diabetes prevalence, incidence, and mortality among the elderly of
      four racial/ethnic groups: whites, blacks, hispanics, and asians.
AB  - OBJECTIVE: To examine diabetes prevalence, incidence, and mortality from 1993 to
      2001 among fee-for-service Medicare beneficiaries > or = 67 years of age.
      RESEARCH DESIGN AND METHODS: This study was a retrospective analysis of a 5%
      random sample of Medicare fee-for-service beneficiaries > or = 65 years of age in
      each year. RESULTS: In 1993, the prevalence of diabetes among those > or = 67
      years of age was 145 cases per 1,000 individuals. By 2001, it was 197/1,000, an
      increase of 36.0%. The 2001 prevalence among Hispanics (334/1,000) was
      significantly higher than among blacks (296/1,000), Asians (243/1,000), and
      whites (184/1,000, P < 0.0001). During the 7-year period the greatest increase in
      diabetes prevalence was among Asians (68.0%). Between 1994 and 2001, the annual
      rate of newly diagnosed elderly individuals with diabetes increased by 36.9%.
      Hispanics had the greatest increase at 55.0%. The mortality rate among
      individuals with diabetes decreased by approximately 5% between 1994 and 2001
      from 92.1/1,000 to 87.2/1,000 (P < 0.001), due to a 6% decrease among whites. No
      decrease in mortality was seen among elderly individuals without diabetes, it was
      55/1,000 in 1994 and 54/1,000 in 2001. CONCLUSIONS: The dramatic increase in the
      incidence and prevalence of diabetes likely reflect a combination of true
      increases, as well as changes in the diagnostic criteria and increased interest
      in diagnosing and appropriately treating diabetes in the elderly. Improved
      treatment may have had an impact on mortality rates among individuals with
      diabetes, although they could have been influenced by the duration of diabetes
      before diagnosis, which has likely decreased. Changes in incidence, prevalence,
      and mortality in elderly individuals with diabetes need to continue to be
      monitored.

PMID- 15451895
TI  - Is patient readiness to change a predictor of improved glycemic control?
AB  - OBJECTIVE: To test the hypothesis that patient readiness to change (RTC) predicts
      future changes in glycemic control in adults with diabetes. RESEARCH DESIGN AND
      METHODS: We linked survey data with HbA1c data for a stratified random sample of
      consenting adults with diabetes. Change in HbA1c from baseline to the 1-year
      follow-up was computed and used as a dependent variable. Linear regression models
      assessed RTC and other patient variables as predictors of HbA1c change. RESULTS:
      Among 617 patients with baseline HbA1c > or = 7% and complete data for analysis,
      RTC predicted subsequent improvement in HbA1c for those with higher physical
      functioning (interaction t = -2.45, P < 0.05). Other factors that predicted HbA1c
      improvement in multivariate linear regression models included higher self
      reported medication adherence (t = -4.41, P < 0.01), higher baseline HbA1c (t = 
      15.08, P < 0.01), and older age (t = -2.61, P < 0.01). CONCLUSIONS: Diabetes RTC
      independently predicts change in HbA1c for patients with high but not for
      patients with low functional health status. Customized use of RTC assessment may
      have potential to improve care.

PMID- 15451896
TI  - Increased diabetes incidence in Greek and Italian migrants to Australia: how much
      can be explained by known risk factors?
AB  - OBJECTIVE: The aims of the study were to determine whether Greek or Italian
      migrants to Australia have an elevated incidence of type 2 diabetes compared with
      Australian-born individuals and to what extent any differences can be explained
      by known risk factors. RESEARCH DESIGN AND METHODS: This was a prospective study
      of 34,097 men and women aged 40-69 years born in Greece, Italy, Australia, or New
      Zealand who were free from diabetes at baseline. For all self-reported cases of
      diabetes at the 4-year follow-up, a confirmation of diagnosis was sought from
      medical practitioners. Of these, anyone for whom there was no evidence against a
      diagnosis of type 2 diabetes was considered a case subject. RESULTS: Follow-up
      was completed by 29,331 (86%) participants, and 334 case subjects were
      identified. The cumulative incidence of type 2 diabetes among Greek (2.6%) and
      Italian (2.4%) migrants was more than three times that in Australian-born (0.7%)
      individuals. After adjusting for age only, the odds ratios (ORs) for being of
      Greek and Italian origin compared with Australian origin were 3.8 (95% CI 2.9
      5.0) and 3.3 (2.6-4.3), respectively. The only known risk factor for type 2
      diabetes that materially affected these ORs was BMI. After adjusting for BMI and
      age, the ORs for being of Greek and Italian origin, respectively, were 2.4 (1.8
      3.2) and 2.0 (1.5-2.6). CONCLUSIONS: Greek and Italian migrants to Australia have
      a more than three times greater incidence of type 2 diabetes than Australian-born
      individuals, and this is only partly explained by BMI. Although weight control
      will remain important for these high-risk groups, identification of other risk
      factors is required.

PMID- 15451897
TI  - Acute hyperglycemia alters mood state and impairs cognitive performance in people
      with type 2 diabetes.
AB  - OBJECTIVE: To examine the effects of acute hyperglycemia on cognitive function
      and mood in people with type 2 diabetes. RESEARCH DESIGN AND METHODS: Twenty
      subjects with type 2 diabetes, median age 61.5 years (range 53.1-72.0), known
      duration of diabetes 5.9 years (range 2.8-11.2), BMI 29.8 kg/m2 (range 22.0
      34.6), and HbA1c 7.5% (range 6.7-8.4) were studied. Treatment modalities varied
      from antidiabetic medications to insulin. A hyperinsulinemic glucose clamp was
      used to maintain arterialized blood glucose at either 4.5 (euglycemia) or 16.5
      mmol/l (hyperglycemia) on two occasions in a randomized and counterbalanced
      fashion. Tests of information processing, immediate and delayed memory, working
      memory, and attention were administered, along with a mood questionnaire, during
      each experimental condition. RESULTS: Speed of information processing, working
      memory, and some aspects of attention were impaired during acute hyperglycemia.
      Subjects were significantly more dysphoric during hyperglycemia, with reduced
      energetic arousal and increased sadness and anxiety. CONCLUSIONS: During acute
      hyperglycemia, cognitive function was impaired and mood state deteriorated in a
      group of people with type 2 diabetes. These findings are of practical importance
      because intermittent or chronic hyperglycemia is common in people with type 2
      diabetes and may interfere with many daily activities through adverse effects on
      cognitive function and mood.

PMID- 15451898
TI  - The treatment of diabetic gastroparesis with botulinum toxin injection of the
      pylorus.
AB  - OBJECTIVE: Gastroparesis is a disorder of delayed gastric emptying that is often
      chronic in nature. Up to 50% of type 1 diabetic subjects have symptoms of
      gastroparesis, which include nausea, vomiting, and early satiety. Elevated
      pyloric pressures may be responsible for delayed gastric emptying in diabetic
      subjects. Botulinum toxin inhibits the release of acetylcholine and produces
      transient paralysis when injected into smooth muscle. The aim of this study was
      to determine whether injection of the pylorus with botulinum toxin in patients
      with diabetic gastroparesis improves symptoms of gastroparesis, alters gastric
      emptying scan time, and/or changes weight and insulin use. RESEARCH DESIGN AND
      METHODS: This was an open-label trial with age- and sex-matched control subjects
      from a tertiary care referral center for patients with gastroparesis. Eight type
      1 diabetic subjects (six women and two men; mean age 41 years; mean years with
      diabetes 25.3) who had failed standard therapy were enrolled. Intervention
      consisted of injection of the pylorus with 200 units of botulinum toxin during
      upper endoscopy. Symptoms, antropyloric manometry, gastric emptying scan times,
      weight, and insulin use were all recorded before intervention and during a 12
      week follow-up period. RESULTS: Seven of the eight patients completed the full 12
      week follow-up period. No complications were noted. Mean symptom scores declined
      from 27 to 12.1 (P < 0.01), whereas the SF-36 physical functioning domain also
      improved (P < 0.05). Four patients noted an increase in insulin use of >5
      units/day. Six of the seven patients gained weight (P = 0.05). Gastric emptying
      scan time improved in four patients. CONCLUSIONS: Botulinum toxin injection of
      the pylorus is safe and improves symptoms in patients with diabetic
      gastroparesis. These results warrant further investigation with a large, double
      blind, placebo-controlled trial.

PMID- 15451899
TI  - Pancreatic beta-cell function and immune responses to insulin after
      administration of intranasal insulin to humans at risk for type 1 diabetes.
AB  - OBJECTIVE: Mucosal administration of insulin retards development of autoimmune
      diabetes in the nonobese diabetic mouse model. We conducted a double-blind
      crossover study in humans at risk for type 1 diabetes to determine if intranasal
      insulin was safe, in particular did not accelerate beta-cell destruction, and
      could induce immune effects consistent with mucosal tolerance. RESEARCH DESIGN
      AND METHODS: A total of 38 individuals, median age 10.8 years, with antibodies to
      one or more pancreatic islet antigens (insulin, GAD65, or tyrosine phosphatase
      like insulinoma antigen 2) were randomized to treatment with intranasal insulin
      (1.6 mg) or a carrier solution, daily for 10 days and then 2 days a week for 6
      months, before crossover. The primary outcome was beta-cell function measured as
      first-phase insulin response (FPIR) to intravenous glucose at 0, 6, and 12 months
      and then yearly; the secondary outcome was immunity to islet antigens, measured
      monthly for 12 months. RESULTS: No local or systemic adverse effects were
      observed. Diabetes developed in 12 participants with negligible beta-cell
      function at entry after a median of 1.1 year. Of the remaining 26, the majority
      had antibodies to two or three islet antigens and FPIR greater than the first
      percentile at entry, as well as beta-cell function that generally remained stable
      over a median follow-up of 3.0 years. Intranasal insulin was associated with an
      increase in antibody and a decrease in T-cell responses to insulin. CONCLUSIONS:
      Results from this pilot study suggest that intranasal insulin does not accelerate
      loss of beta-cell function in individuals at risk for type 1 diabetes and induces
      immune changes consistent with mucosal tolerance to insulin. These findings
      justify a formal trial to determine if intranasal insulin is immunotherapeutic
      and retards progression to clinical diabetes.

PMID- 15451900
TI  - Efficacy and safety of inhaled insulin (exubera) compared with subcutaneous
      insulin therapy in patients with type 2 diabetes: results of a 6-month,
      randomized, comparative trial.
AB  - OBJECTIVE: Glycemic control using inhaled, dry-powder insulin plus a single
      injection of long-acting insulin was compared with a conventional regimen in
      patients with type 2 diabetes, which was previously managed with at least two
      daily insulin injections. RESEARCH DESIGN AND METHODS: Patients were randomized
      to 6 months' treatment with either premeal inhaled insulin plus a bedtime dose of
      Ultralente (n = 149) or at least two daily injections of subcutaneous insulin
      (mixed regular/NPH insulin; n = 150). The primary efficacy end point was the
      change in HbA1c from baseline to the end of study. RESULTS: HbA1c decreased
      similarly in the inhaled (-0.7%) and subcutaneous (-0.6%) insulin groups
      (adjusted treatment group difference: -0.07%, 95% CI -0.32 to 0.17). HbA1c < 7.0%
      was achieved in more patients receiving inhaled (46.9%) than subcutaneous (31.7%)
      insulin (odds ratio 2.27, 95% CI 1.24-4.14). Overall hypoglycemia (events per
      subject-month) was slightly lower in the inhaled (1.4 events) than in the
      subcutaneous (1.6 events) insulin group (risk ratio 0.89, 95% CI 0.82-0.97), with
      no difference in severe events. Other adverse events, with the exception of
      increased cough in the inhaled insulin group, were similar. No difference in
      pulmonary function testing was seen. Further studies are underway to assess
      tolerability in the longer term. Insulin antibody binding increased more in the
      inhaled insulin group. Treatment satisfaction was greater in the inhaled insulin
      group. CONCLUSIONS: Inhaled insulin appears to be effective, well tolerated, and
      well accepted in patients with type 2 diabetes and provides glycemic control
      comparable to a conventional subcutaneous regimen.

PMID- 15451901
TI  - Insulin glulisine provides improved glycemic control in patients with type 2
      diabetes.
AB  - OBJECTIVE: Insulin glulisine is a novel analog of human insulin designed for use
      as a rapid-acting insulin. This study compared the safety and efficacy of
      glulisine with regular human insulin (RHI) in combination with NPH insulin.
      RESEARCH DESIGN AND METHODS: In total, 876 relatively well-controlled patients
      with type 2 diabetes (mean HbA1c 7.55%) were randomized and treated with
      glulisine/NPH (n = 435) or RHI/NPH (n = 441) for up to 26 weeks in this
      randomized, multicenter, multinational, open-label, parallel-group study.
      Subjects were allowed to continue the same dose of prestudy regimens of oral
      antidiabetic agent (OAD) therapy (unless hypoglycemia necessitated a dose
      change). RESULTS: A slightly greater reduction from baseline to end point of
      HbA1c was seen in the glulisine group versus RHI (-0.46 vs. -0.30% with RHI; P =
      0.0029). Also, at end point, lower postbreakfast (156 vs. 162 mg/dl [8.66 vs.
      9.02 mmol/l]; P < 0.05) and postdinner (154 vs. 163 mg/dl [8.54 vs. 9.05 mmol/l];
      P < 0.05) blood glucose levels were noted. Symptomatic hypoglycemia (overall,
      nocturnal, and severe) and weight gain were comparable between the two treatment
      groups. There were no between-group differences in baseline-to-end point changes
      in insulin dose. CONCLUSIONS: Twice-daily glulisine associated with NPH can
      provide small improvements in glycemic control compared with RHI in patients with
      type 2 diabetes who are already relatively well controlled on insulin alone or
      insulin plus OADs. The clinical relevance of such a difference remains to be
      established.

PMID- 15451902
TI  - Aldose reductase inhibition by AS-3201 in sural nerve from patients with diabetic
      sensorimotor polyneuropathy.
AB  - OBJECTIVE: The primary purpose of this investigation was to determine whether AS
      3201, a new aldose reductase inhibitor, penetrates the sural nerve and inhibits
      sorbitol and fructose accumulation in patients with diabetic sensorimotor
      polyneuropathy (DSP). An additional aim was to determine whether any changes in
      nerve function would manifest with AS-3201 therapy. RESEARCH DESIGN AND METHODS:
      Patients with mild to moderate DSP based on nerve conduction studies were
      randomized into one of three treatment groups in a double-blind fashion: placebo
      or AS-3201 at 5 or 20 mg/day. After 12 weeks of administration, the sural nerve
      was biopsied for measurement of sorbitol, fructose, and AS-3201. RESULTS: At
      baseline, no important clinical, electrophysiological, or laboratory differences
      were found between the three groups. The nerve sorbitol concentration of 3.14 x
      10(-2) nmol/mg wet nerve in patients in the placebo group was inhibited by 65 and
      84% in patients on AS-3201 at 5 and 20 mg/day, respectively (P < 0.001). Fructose
      levels were similarly inhibited. Sensory nerve conduction velocities improved by
      > or = 1 m/s (P < 0.05). CONCLUSIONS: AS-3201 penetrates the sural nerve and
      inhibits sorbitol accumulation in patients with DSP. Additional studies are
      needed to confirm the electrophysiological suggestion that AS-3201 delays
      progression or leads to regression of DSP.

PMID- 15451903
TI  - Plantar fat-pad displacement in neuropathic diabetic patients with toe deformity:
      a magnetic resonance imaging study.
AB  - OBJECTIVE: The aim of this study was to quantify the association between
      claw/hammer toe deformity and changes in submetatarsal head (sub-MTH) fat-pad
      geometry in diabetic neuropathic feet. RESEARCH DESIGN AND METHODS: Thirteen
      neuropathic diabetic subjects (mean age 56.2 years) with toe deformity, 13 age-
      and sex-matched neuropathic diabetic control subjects without deformity, and 13
      age- and sex-matched healthy control subjects without deformity were examined.
      From high-resolution sagittal plane magnetic resonance images of the second and
      third ray of the foot, toe angle (a measure of deformity), sub-MTH fat-pad
      thickness, and subphalangeal fat-pad thickness were measured. The ratio of these
      thicknesses was used to indicate fat-pad displacement. RESULTS: Sub-MTH fat pads
      were significantly thinner (2.5 +/- 1.3 vs. 6.0 +/- 1.4 mm, P < 0.001) and
      subphalangeal fat pads significantly thicker (9.1 +/- 1.9 vs. 7.6 +/- 1.2 mm, P <
      0.005) in the neuropathic group with deformity compared with neuropathic control
      subjects. As a result, thickness ratio was substantially smaller in the deformity
      group: 0.28 +/- 0.14 vs. 0.79 +/- 0.14 in neuropathic control subjects (P <
      0.001). A significant correlation of 0.85 was present between toe angle and
      thickness ratio (P < 0.001). No significant differences were found between
      neuropathic and healthy control subjects. CONCLUSIONS: This study shows a distal
      displacement and subsequent thinning of the sub-MTH fat pads in neuropathic
      diabetic patients with toe deformity and suggests that, as a result, the capacity
      of the tissue in this region to reduce focal plantar pressure is severely
      compromised. This condition is likely to increase the risk of plantar ulceration
      in these patients.

PMID- 15451904
TI  - Atrophy of foot muscles: a measure of diabetic neuropathy.
AB  - OBJECTIVE: Diabetic neuropathy is a length-dependent process that leads to
      reduced muscle strength and atrophy of leg muscles in some patients. We
      hypothesized that intrinsic foot muscles are atrophied in diabetic neuropathy and
      that the degree of atrophy is a measure of motor dysfunction closely related to
      the neuropathic process. RESEARCH DESIGN AND METHODS: Consecutive cross-sectional
      magnetic resonance images of the nondominant foot were obtained for stereological
      determination of the total volume of the intrinsic foot muscles (VFM) in 23 long
      term diabetic patients with (n = 15) and without (n = 8) chronic neuropathy and
      in 23 matched healthy nondiabetic control subjects. Based on clinical
      examination, nerve conduction studies, and quantitative sensory examination, a
      neuropathy rank-sum score was calculated for each patient. RESULTS: Total VFM was
      86 +/- 52, 165 +/- 34, and 168 +/- 42 cm3 in neuropathic patients, nonneuropathic
      patients, and healthy control subjects, respectively (P < 0.001). There was a
      close inverse relationship between the neuropathy rank-sum score and the VFM (r =
      -0.75, P < 1 x 10(-5)). CONCLUSIONS: Total volume of the foot muscles is halved
      in patients with diabetic neuropathy. Atrophy of foot muscles is closely related
      to the severity of neuropathy and reflects motor dysfunction.

PMID- 15451905
TI  - Thermal thresholds predict painfulness of diabetic neuropathies.
AB  - OBJECTIVE: Pathophysiology explaining pain in diabetic neuropathy (DN) is still
      unknown. RESEARCH DESIGN AND METHODS: Thirty patients with peripheral DN (17 men
      and 13 women; mean age 52.4 +/- 2.5 years) were investigated. Fifteen patients
      had neuropathic pain, and 15 patients were free of pain. Patients were followed
      over 2 years and examined at the beginning and thereafter every 6 months.
      Clinical severity and painfulness of the DN were assessed by the neuropathy
      impairment score and visual analog scales (VASs). Cold and warm perception
      thresholds as well as heat pain thresholds were obtained for evaluation of Adelta
      and C-fibers. Nerve conduction velocities (NCVs) and vibratory thresholds were
      recorded for analysis of thickly myelinated fibers. Moreover, for assessment of
      cardiac vagal function, heart rate variability (HRV) was evaluated. In order to
      reduce day-to-day variability of pain, mean values of the five time points over 2
      years were calculated and used for further analysis. Data were compared with an
      age- and sex-matched control group of healthy volunteers. RESULTS: There were
      significant differences regarding electrophysiological studies, HRV and
      quantitative sensory testing (QST) between patients and healthy control subjects
      (P < 0.001). Generally, patients with neuropathic pain were indistinguishable
      from pain-free patients. In the pain group, however, VAS pain ratings were
      correlated to the impairment of small-fiber function (cold detection thresholds,
      P = 0.02; warm detection thresholds, P = 0.056). CONCLUSIONS: Intensity of pain
      in painful DN seems to depend on small nerve fiber damage and deafferentation.

PMID- 15451906
TI  - Adiponectin concentrations in sera from patients with type 2 diabetes are
      negatively associated with sympathovagal balance as evaluated by power spectral
      analysis of heart rate variation.
AB  - OBJECTIVE: To investigate whether cardiac autonomic activity, particularly
      sympathovagal balance as estimated by power spectral analysis (PSA) of heart rate
      variation (HRV), is associated with serum adiponectin concentrations in patients
      with type 2 diabetes. RESEARCH DESIGN AND METHODS: We studied 105 patients with
      type 2 diabetes (51 women and 54 men). Serum adiponectin concentrations were
      measured by sandwich enzyme-linked immunosorbent assay. HRV was determined
      automatically every 5 min over 24 h using Holter electrocardiographic recording.
      PSA of R-R intervals was performed using fast Fourier transformation. Low
      frequency (both sympathetic and parasympathetic activities), high- frequency
      (pure parasympathetic activity), and the ratio of low-frequency-to-high-frequency
      power (LF-to-HF ratio), an index of sympathovagal balance, were used as indexes
      of cardiac autonomic activity. RESULTS: We found no significant correlation
      between serum adiponectin and low-frequency or high-frequency power in patients
      with diabetes. Serum adiponectin concentration correlated negatively with the 24
      h LF-to-HF ratio (r = -0.343, P = 0.0009) and creatinine clearance (r = -0.411, P
      < 0.0001). Serum adiponectin concentrations were significantly higher in patients
      with overt albuminuria than in those with normoalbuminuria or microalbuminuria.
      In multivariate analysis controlling for sex, BMI, glycemic control, lipid
      profile, and renal function, serum adiponectin concentration showed an
      independent negative association with 24-h LF-to-HF ratio (beta = -0.332, P =
      0.020). Furthermore, sex, HDL cholesterol, and renal function retained
      significant influence on the serum adiponectin concentration in patients with
      diabetes. CONCLUSIONS: Sympathovagal balance favoring relative sympathetic
      activation was associated with low serum concentrations of adiponectin in
      patients with type 2 diabetes.

PMID- 15451907
TI  - The effect of diabetes on B-type natriuretic peptide concentrations in patients
      with acute dyspnea: an analysis from the Breathing Not Properly Multinational
      Study.
AB  - OBJECTIVE: Diabetes has been implicated in reduced myocardial compliance and
      changes in the intercellular matrix of the myocardium. We determined the effect
      of diabetes on B-type natriuretic peptide (BNP) concentrations in patients
      presenting to the emergency department with dyspnea. RESEARCH DESIGN AND METHODS:
      The Breathing Not Properly Multinational Study was a prospective evaluation of
      1,586 patients. A subset of 922 patients was obtained and subdivided into the
      following groups: group 1 (n = 324), neither diabetes nor heart failure; group 2
      (n = 107), diabetes and no heart failure; group 3 (n = 247), no diabetes and
      heart failure; group 4 (n = 183), both diabetes and heart failure; group 5 (n =
      41), heart failure history with no diabetes; and group 6 (n = 20), heart failure
      history with diabetes. Patients from groups 1, 3, and 5 were matched to groups 2,
      4, and 6, respectively, to have the same mean age, sex distribution, BMI, renal
      function, and New York Heart Association (NYHA) classification (for heart
      failure). RESULTS: There was no significant difference in median BNP levels
      between diabetes and no diabetes among no heart failure patients (32.4 vs.32.9
      pg/ml), heart failure patients (587 vs. 494 pg/ml), and those with a heart
      failure history (180 vs. 120 pg/ml). Receiver-operating characteristic curve
      analysis of the area under the curve for BNP was not different in diabetic versus
      nondiabetic patients (0.888 vs. 0.878, respectively). However, in a multivariate
      model, diabetes was an independent predictor of a final diagnosis of heart
      failure (odds ratio 1.51, 95% CI 1.03-2.02; P < 0.05). CONCLUSIONS: History of
      diabetes does not impact BNP levels measured in patients with acute dyspnea in
      the emergency department. Despite the impact of diabetes on the cardiovascular
      system, diabetes does not appear to confound BNP levels in the emergency
      department diagnosis of heart failure.

PMID- 15451908
TI  - Beta-cell dysfunction in classic transient neonatal diabetes is characterized by
      impaired insulin response to glucose but normal response to glucagon.
AB  - OBJECTIVE: To investigate beta-cell function and the long-term health of four
      case subjects presenting with chromosome 6-associated transient neonatal diabetes
      (TND). RESEARCH DESIGN AND METHODS: Two unrelated case subjects presenting with
      paternal uniparental isodisomy of chromosome 6 (UPD6) and two siblings with a
      paternally inherited duplication of 6q24 were studied. Three case subjects
      presented with neonatal diabetes that recurred at 4-17 years, while diabetes was
      incidentally discovered in the other case subject at 14 years of age. beta-Cell
      function was investigated after diabetes relapse by means of an oral glucose
      tolerance test (OGTT), an intravenous glucose tolerance test (IVGTT), and
      glucagon tests. The quantitative insulin sensitivity check index (QUICKI) was
      calculated from fasting blood samples as an estimate of insulin sensitivity.
      RESULTS: beta-Cell function was investigated at diabetes relapse in two case
      subjects: the insulin response to both an OGTT and IVGTT was low, whereas the
      basal levels of C-peptide were normal. No evidence of insulin resistance was
      found. Residual beta-cell function was further explored by a glucagon test in all
      subjects at the age of 16-28 years and was found to be normal. Final height was
      within the normal percentiles, whereas one case, who had been poorly controlled
      since puberty, presented with diabetes-related microvascular complications.
      CONCLUSIONS: In patients with chromosome 6-associated TND, the beta-cell is
      preserved and able to secrete insulin through the stimulatory G protein pathway
      while exhibiting a specific defect of insulin secretion after glucose
      stimulation. This form of diabetes can be managed with insulin or diet, although
      new therapeutic agents (glucagon-like synthetic analogs) may prove useful in the
      future. Lack of treatment leads to long-lasting hyperglycemia without the risk of
      ketoacidosis but associated with microangiopathy in adult life.

PMID- 15451909
TI  - Stiffness and impaired blood flow in lower-leg arteries are associated with
      severity of coronary artery calcification among asymptomatic type 2 diabetic
      patients.
AB  - OBJECTIVE: To clarify whether stiffness and impaired blood flow in lower-leg
      arteries are associated with severity of coronary artery calcification among
      asymptomatic diabetic patients. RESEARCH DESIGN AND METHODS: We enrolled 102
      asymptomatic type 2 diabetic patients with no history of cardiovascular
      complications consecutively admitted to our hospital. Agatston coronary artery
      calcium (CAC) score, as a marker of coronary artery calcification, was obtained
      using electron-beam computed tomography. Total flow volume and resistive index,
      as an index of vascular resistance, at the popliteal artery were evaluated using
      gated two-dimensional cine-mode phase-contrast magnetic resonance imaging.
      Brachial-ankle pulse-wave velocity (PWV), as an index of distensibility in the
      lower-extremity arteries, was also measured using an automatic device. RESULTS:
      When the patients were grouped according to CAC scores of 0-10 (n = 54), 11-100
      (n = 25), and > 100 (n = 23), those with the highest scores, which is considered
      to show possible coronary artery disease, showed the highest brachial-ankle PWV
      (P < 0.001) and resistive index (P < 0.001) and the lowest total flow volume (P <
      0.001) among the groups. Simple linear regression analyses showed that both
      brachial-ankle PWV (r = 0.508, P < 0.001) and resistive index (r = 0.500, P <
      0.001) were positively correlated and total flow volume (r = -0.528, P < 0.001)
      was negatively correlated with the log-transformed CAC score. Receiver operator
      characteristic curve analyses indicated that 1,800 cm/s for brachial-ankle PWV,
      1.03 for resistive index, and 70 ml/min for total flow volume were diagnostic
      values for identifying patients with the highest scores. CONCLUSIONS:
      Quantitatively assessed stiffness and impaired blood flow in lower-leg arteries
      may help identify diabetic patients with possible coronary artery disease.

PMID- 15451910
TI  - Increased 24-h energy expenditure in type 2 diabetes.
AB  - OBJECTIVE: The aim of this study was to determine whether overweight and obese
      individuals with type 2 diabetes have higher basal and 24-h energy expenditure
      compared with healthy control subjects before and after adjustment for body
      composition, spontaneous physical activity (SPA), sex, and age. RESEARCH DESIGN
      AND METHODS: Data from 31 subjects with type 2 diabetes and 61 nondiabetic
      control subjects were analyzed. The 24-h energy expenditure, basal metabolic rate
      (BMR), and sleeping energy expenditure (EEsleep) between 1:00 a.m. and 6:00 a.m.
      were measured in whole-body respiratory chambers. Body composition was assessed
      by dual-energy X-ray absorptiometry (DXA). RESULTS: No significant differences in
      unadjusted EEsleep, BMR, and 24-h energy expenditure were observed between the
      type 2 diabetic group and the control group. After adjustment for fat-free mass
      (FFM), fat mass, SPA, sex, and age, EEsleep and BMR were, respectively, 7.7 and
      6.9% higher in the type 2 diabetic group compared with the control group. This
      was equivalent to 144 +/- 40 kcal/day (P = 0.001) and 139 +/- 61 kcal/day (P =
      0.026), respectively. Adjusted 24-h energy expenditure was 6.5% higher in the
      type 2 diabetic group compared with the nondiabetic control subjects (2,679 +/-
      37 vs. 2,515 +/- 23 kcal/day, P = 0.002). In multiple regression analyses, FFM,
      fat mass, SPA, and diabetes status were all significant determinants of EEsleep
      and 24-h energy expenditure, explaining 83 and 81% of the variation,
      respectively. CONCLUSIONS: This study confirms reports in Pima Indians that basal
      and 24-h energy expenditure adjusted for body composition, SPA, sex, and age are
      higher in individuals with type 2 diabetes compared with nondiabetic control
      subjects and may be even more pronounced in Caucasians.

PMID- 15451911
TI  - Serum ferritin and risk of the metabolic syndrome in U.S. adults.
AB  - OBJECTIVE: We examined the relationship among iron stores, the metabolic
      syndrome, and insulin resistance. RESEARCH DESIGN AND METHODS: We conducted a
      cross-sectional study of 6,044 adults >20 years of age who participated in the
      Third National Health and Nutrition Examination Survey. Metabolic syndrome was
      defined as the presence of at least three of the following: elevated blood
      pressure, low HDL cholesterol, elevated serum triglycerides, elevated plasma
      glucose, and abdominal obesity. Insulin resistance was estimated using
      homeostasis model assessment (for insulin resistance), fasting insulin, and
      triglyceride-to-HDL cholesterol ratio. RESULTS: After excluding individuals with
      likely hemochromatosis, mean serum ferritin values in premenopausal women,
      postmenopausal women, and men were 33.6, 93.4, and 139.9 microg/l, respectively.
      Metabolic syndrome was more common in those with the highest compared with the
      lowest levels of serum ferritin in premenopausal women (14.9 vs. 6.4%, P =
      0.002), postmenopausal women (47.5 vs. 28.2%, P < 0.001), and men (27.3 vs.
      13.8%, P < 0.001). Insulin resistance also increased across quartiles of serum
      ferritin for men and postmenopausal women and persisted after adjustment for age,
      race/ethnicity, C-reactive protein, smoking, alcohol intake, and BMI.
      CONCLUSIONS: Elevated iron stores were positively associated with the prevalence
      of the metabolic syndrome and with insulin resistance.

PMID- 15451912
TI  - The metabolic syndrome defined by factor analysis and incident type 2 diabetes in
      a chinese population with high postprandial glucose.
AB  - OBJECTIVE: The aim of this study was to examine how the major components of the
      metabolic syndrome relate to each other and to the development of diabetes using
      factor analysis. RESEARCH DESIGN AND METHODS: The screening survey for type 2
      diabetes was conducted in 1994, and a follow-up study of nondiabetic individuals
      at baseline was carried out in 1999 in the Beijing area. Among 934 nondiabetic
      and 305 diabetic subjects at baseline, factor analysis was performed using the
      principle components analysis with varimax orthogonal rotation of continuously
      distributed variables considered to represent the components of the metabolic
      syndrome. Fasting insulin was used as a marker for insulin resistance. Of the 559
      subjects without diabetes at baseline, 129 developed diabetes during the 5-year
      follow-up. Factors identified at baseline were used as independent variables in
      univariate and multivariate logistic regression models to determine risk factor
      clusters predicting the development of diabetes. RESULTS: Four factors were
      identified in nondiabetic and diabetic subjects. Fasting insulin levels, BMI, and
      waist-to-hip ratio were associated with one factor. Systolic and diastolic blood
      pressures were associated with the second factor. Two-hour postload plasma
      glucose (2-h PG) and serum insulin and fasting plasma glucose were associated
      with the third factor. Serum total cholesterol and triglycerides were associated
      with the fourth factor. The first and the third factors predicted the development
      of diabetes. In diabetic patients at baseline, the combination of systolic and
      diastolic blood pressure was the most important factor, and urinary albumin
      excretion rate clustered with fasting and 2-h PG levels. CONCLUSIONS: Insulin
      resistance alone does not underlie all features of the metabolic syndrome.
      Different physiological processes associated with various components of the
      metabolic syndrome contain unique information about diabetes risk. Microalbunuria
      is more likely to be a complication of type 2 diabetes or hypertension than a
      marker for the metabolic syndrome.

PMID- 15451913
TI  - Prevalence and trends of a metabolic syndrome phenotype among u.s. Adolescents,
      1999-2000.
AB  - OBJECTIVE: To determine the prevalence of a metabolic syndrome phenotype among
      U.S. adolescents using the most recent national data and to examine trends in
      metabolic syndrome prevalence. RESEARCH DESIGN AND METHODS: Analysis of data on
      991 adolescents (aged 12-19 years) who had fasted for at least 6 h, from the
      National Health and Nutrition Examination Survey (NHANES 1999-2000). The
      metabolic syndrome was determined using the National Cholesterol Education
      Program (Adult Treatment Panel III) definition modified for age. RESULTS: The
      overall prevalence of a metabolic syndrome phenotype among U.S. adolescents
      increased from 4.2% in NHANES III (1988-1992) to 6.4% in NHANES 1999-2000 (P <
      0.001). The syndrome was more prevalent (P < 0.01) in male than female
      adolescents (9.1 vs. 3.7%) and was found in 32.1% of overweight adolescents (BMI
      > or = 95th percentile for age and sex), compared with 7.1% of adolescents at
      risk for overweight (BMI between 85th and 95th percentiles) (P < 0.001). Based on
      population-weighted estimates, > 2 million U.S. adolescents currently have a
      metabolic syndrome phenotype. CONCLUSIONS: The prevalence of a metabolic syndrome
      phenotype has increased significantly over the past decade among U.S. adolescents
      and is particularly prevalent (> 30%) in overweight adolescents. These findings
      have important implications for public health because of the well-known health
      risks associated with the metabolic syndrome in adults.

PMID- 15451914
TI  - Increasing prevalence of the metabolic syndrome among u.s. Adults.
AB  - OBJECTIVE: The prevalence of the metabolic syndrome is high among U.S. adults.
      Our purpose was to determine whether the prevalence of this syndrome has changed
      since 1988-1994. RESEARCH DESIGN AND METHODS: A total of 6,436 men and women aged
      > or = 20 years from the National Health and Nutrition Examination Survey
      (NHANES) III (1988-1994) and 1,677 participants from NHANES 1999-2000 were
      included in the analyses. We used the definition of the metabolic syndrome
      developed by the Third Report of the National Cholesterol Education Program
      Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in
      Adults. RESULTS: The unadjusted prevalence of the metabolic syndrome was 23.1% in
      NHANES III and 26.7% in NHANES 1999-2000 (P = 0.043), and the age-adjusted
      prevalences were 24.1 and 27.0% (P = 0.088), respectively. The age-adjusted
      prevalence increased by 23.5% among women (P = 0.021) and 2.2% among men (P =
      0.831). Increases in high blood pressure, waist circumference, and
      hypertriglyceridemia accounted for much of the increase in the prevalence of the
      metabolic syndrome, particularly among women. CONCLUSIONS: The increased
      prevalence of the metabolic syndrome is likely to lead to future increases in
      diabetes and cardiovascular disease.

PMID- 15451915
TI  - Circulating adiponectin and resistin levels in relation to metabolic factors,
      inflammatory markers, and vascular reactivity in diabetic patients and subjects
      at risk for diabetes.
AB  - OBJECTIVE: Adiponectin and resistin, two recently discovered adipocyte-secreted
      hormones, may link obesity with insulin resistance and/or metabolic and
      cardiovascular risk factors. We performed a cross-sectional study to investigate
      the association of adiponectin and resistin with inflammatory markers,
      hyperlipidemia, and vascular reactivity and an interventional study to
      investigate whether atorvastatin mediates its beneficial effects by altering
      adiponectin or resistin levels. RESEARCH DESIGN AND METHODS: Associations among
      vascular reactivity, inflammatory markers, resistin, and adiponectin were
      assessed cross-sectionally using fasting blood samples obtained from 77 subjects
      who had diabetes or were at high risk to develop diabetes. The effect of
      atorvastatin on adiponectin and resistin levels was investigated in a 12-week
      long randomized, double-blind, placebo-controlled study. RESULTS: In the cross
      sectional study, we confirm prior positive correlations of adiponectin with HDL
      and negative correlations with BMI, triglycerides, C-reactive protein (CRP), and
      plasma activator inhibitor (PAI)-1 and report a negative correlation with tissue
      plasminogen activator. The positive association with HDL and the negative
      association with PAI-1 remained significant after adjusting for sex and BMI. We
      also confirm prior findings of a negative correlation of resistin with HDL and
      report for the first time a positive correlation with CRP. All of these
      associations remained significant after adjusting for sex and BMI. No
      associations of adiponectin or resistin with any aspects of vascular reactivity
      were detected. In the interventional study, atorvastatin decreased lipid and CRP
      levels, but adiponectin and resistin were not specifically altered. CONCLUSIONS:
      We conclude that adiponectin is significantly associated with inflammatory
      markers, in part, through an underlying association with obesity, whereas
      resistin's associations with inflammatory markers appear to be independent of
      BMI. Lipid profile and inflammatory marker changes produced by atorvastatin
      cannot be attributed to changes of either adiponectin or resistin.

PMID- 15451916
TI  - Antihypertensive therapy and incidence of type 2 diabetes in an elderly cohort.
AB  - OBJECTIVE: The aim of this study was to determine whether the incidence of type 2
      diabetes differed among elderly users of four major antihypertensive drug
      classes. RESEARCH DESIGN AND METHODS: This was a retrospective, observational
      cohort study of previously untreated elderly patients (aged > or = 66 years)
      identified as new users of an antihypertensive drug class between April 1995 and
      March 2000. Using a Cox proportional hazards model, the primary analysis compared
      diabetes incidence in users of ACE inhibitors, beta-blockers, and calcium channel
      blockers (CCBs), with thiazide diuretics allowed as second-line therapy. In the
      secondary analysis, thiazide diuretics were added as a fourth study group.
      RESULTS: In the multivariable-adjusted primary analysis (n = 76,176), neither ACE
      inhibitor use (hazard ratio 0.96 [95% CI 0.84-1.1]) nor beta-blocker use (0.86
      [0.74-1.0]) was associated with a statistically significant difference in type 2
      diabetes incidence compared with the CCB control group. In the secondary analysis
      (n = 100,653), compared with CCB users, type 2 diabetes incidence was not
      significantly different between users of ACE inhibitors (0.97 [0.83-1.1]), beta
      blockers (0.84 [0.7-1.0]), or thiazide diuretics (1.0 [0.89-1.2]). CONCLUSIONS:
      Type 2 diabetes incidence did not significantly differ among users of the major
      antihypertensive drug classes in this elderly, population-based administrative
      cohort. These results do not support the theory that different antihypertensive
      drug classes are relatively more or less likely to cause diabetes.

PMID- 15451917
TI  - Incidence of diabetes in middle-aged men is related to sleep disturbances.
AB  - OBJECTIVE: Sleep deprivation in healthy men has been experimentally found to
      result in disturbances in glucose metabolism and in sympathovagal imbalance. The
      aim of the present study was to investigate whether sleep disturbances and
      elevated resting heart rate are associated with increased risk of developing
      diabetes. RESEARCH DESIGN AND METHODS: A group of 6,599 initially healthy,
      nondiabetic men aged 44.5 +/- 4.0 years took part in a prospective, population
      based study in Malmo, Sweden. The incidence of diabetes during a mean follow-up
      of 14.8 +/- 2.4 years was examined in relation to self-reported difficulties in
      falling asleep and resting heart rate at baseline. Diabetes was assessed at
      follow-up in all subjects by questionnaire and in a subgroup of 1,551 men by
      blood glucose measurement. RESULTS: A total of 615 (9.3%) subjects reported
      either difficulties in falling asleep or regular use of hypnotics (seen as
      markers of sleep disturbances), and 158 (2.4%) subjects reported both of these.
      Altogether, 281 (4.3%) of the men developed diabetes during the follow-up period.
      Logistic regression models showed difficulties in falling asleep or regular use
      of hypnotics (odds ratio [OR] 1.52 [95% CI 1.05-2.20]) and resting heart rate (OR
      per 10 bpm 1.13 [0.99-1.30]) to be associated with development of diabetes when
      full adjustments were made for baseline age, biological risk factors, lifestyle,
      family history of diabetes, and social class. CONCLUSIONS: The results suggest
      that sleep disturbances and, possibly, elevated resting heart rate, in middle
      aged men, are associated with an increased risk of diabetes.

PMID- 15451918
TI  - What is a normal glucose value? Differences in indexes of plasma glucose
      homeostasis in subjects with normal fasting glucose.
AB  - OBJECTIVE: To evaluate differences in indexes of plasma glucose/insulin
      homeostasis and cardiovascular disease risk factors among subjects with normal
      fasting glucose (NFG), impaired fasting glucose, or glucose intolerance. Although
      individuals with fasting plasma glucose (FPG) concentrations > 5.4 mmol/l but <
      6.1 mmol/l have been shown to have an increased risk of developing type 2
      diabetes over 5 years, little is known about glucose metabolism abnormalities in
      this population. RESEARCH DESIGN AND METHODS: We compared insulin secretion and
      insulin sensitivity using several indexes derived from an oral glucose tolerance
      test (OGTT) in 668 subjects from the Quebec Family Study who had varying degrees
      of FPG. RESULTS: There was a progressive decline in indexes of beta-cell function
      and insulin sensitivity when moving from NFG to type 2 diabetes. Compared with
      subjects with low NFG (FPG < 4.9 mmol/l), subjects with high NFG (FPG 5.3-6.1
      mmol/l) were more insulin resistant (P < 0.01), had higher insulin and C-peptide
      responses during an OGTT (P < 0.05), and had reduced insulin secretion (corrected
      for insulin resistance). Subjects with high NFG were also characterized by higher
      plasma triglyceride levels and reduced HDL cholesterol concentrations and by a
      smaller LDL particle size. All these differences remained significant, even after
      adjustment for age, sex, BMI, and waist circumference. In addition, subjects with
      mid NFG (FPG 4.9-5.3 mmol/l) were characterized by impaired insulin secretion,
      decreased insulin sensitivity, higher triglyceride concentrations, and lower HDL
      cholesterol concentrations compared with subjects with low NFG. CONCLUSIONS:
      Independent of age, sex, and adiposity, there are differences in indexes of
      plasma glucose/insulin homeostasis and in cardiovascular risk factors among
      subjects with low, mid, and high NFG, suggesting the presence, in the upper
      normal glucose range, of abnormalities in glucose homeostasis, which may
      predispose to type 2 diabetes.

PMID- 15451919
TI  - Chronic obstructive pulmonary disease, asthma, and risk of type 2 diabetes in
      women.
AB  - OBJECTIVE: Inflammation plays a key role in chronic obstructive pulmonary disease
      (COPD) and asthma. Increasing evidence points toward a role of inflammation in
      the pathogenesis of type 2 diabetes. We wanted to determine the relation of COPD
      and asthma with the development of type 2 diabetes. RESEARCH DESIGN AND METHODS:
      The Nurses' Health Study is a prospective cohort study. From 1988-1996, 103,614
      female nurses were asked biennially about a physician diagnosis of emphysema,
      chronic bronchitis, asthma, and diabetes. RESULTS: During 8 years of follow-up,
      we documented a total of 2,959 new cases of type 2 diabetes. The risk of type 2
      diabetes was significantly higher for patients with COPD than those without
      (multivariate relative risk 1.8, 95% CI 1.1-2.8). By contrast, the risk of type 2
      diabetes among asthmatic patients was not increased (1.0, 0.8-1.2). The asthma
      results remained nonsignificant even when we evaluated diabetes risk by duration
      of asthma exposure. CONCLUSIONS: Our findings suggest that COPD may be a risk
      factor for developing type 2 diabetes. Differences in the inflammation and
      cytokine profile between COPD and asthma might explain why COPD, but not asthma,
      is associated with increased risk of type 2 diabetes.

PMID- 15451920
TI  - The accuracy of clinical assessment of dehydration during diabetic ketoacidosis
      in childhood.

PMID- 15451921
TI  - Leptin-to-adiponectin ratio as a potential atherogenic index in obese type 2
      diabetic patients.

PMID- 15451922
TI  - Lymphocyte and plasma vitamin C levels in type 2 diabetic patients with and
      without diabetes complications.

PMID- 15451923
TI  - Racial/ethnic differences in leisure-time physical activity levels among
      individuals with diabetes.

PMID- 15451924
TI  - Quality of life, treatment satisfaction, and treatment preference associated with
      use of a pen device delivering a premixed 70/30 insulin aspart suspension (aspart
      protamine suspension/soluble aspart) versus alternative treatment strategies.

PMID- 15451925
TI  - Relation of nonalcoholic hepatic steatosis to early carotid atherosclerosis in
      healthy men: role of visceral fat accumulation.

PMID- 15451926
TI  - White blood cells in obesity and diabetes: effects of weight loss and
      normalization of glucose metabolism.

PMID- 15451927
TI  - Differences in serum ionized and total magnesium values during chronic renal
      failure between nondiabetic and diabetic patients: a cross-sectional study.

PMID- 15451928
TI  - Increased carotid intima-media thickness and stiffness in obese children.

PMID- 15451929
TI  - Changes in circulating postprandial proinflammatory cytokine concentrations in
      diet-controlled type 2 diabetes and the effect of ingested fat.

PMID- 15451930
TI  - Association of birth weight and type 2 diabetes in Rochester, Minnesota.

PMID- 15451931
TI  - Monocyte adhesion to decidual endothelial cells is increased in pregnancies
      complicated by type 1 diabetes but not by gestational diabetes.

PMID- 15451932
TI  - Metabolic syndrome among children and adolescents aged 10-18 years.

PMID- 15451933
TI  - Physical activity/exercise and type 2 diabetes.

PMID- 15451934
TI  - Diabetic retinopathy.

PMID- 15451935
TI  - Gut-derived incretin hormones and new therapeutic approaches.

PMID- 15451936
TI  - Prognostic factors of sudden sensorineural hearing loss in diabetic patients.

PMID- 15451937
TI  - Please, let my doctor be obese: associations between the characteristics of
      general practitioners and their patients with type 2 diabetes.

PMID- 15451938
TI  - Gastric bypass surgery in severely obese type 1 diabetic patients.

PMID- 15451939
TI  - Dysadipocytokinemia in werner syndrome and its recovery by treatment with
      pioglitazone.

PMID- 15451940
TI  - Effect of alpha-linolenic acid-containing linseed oil on coagulation in type 2
      diabetes.

PMID- 15451941
TI  - Use of arterial transfer functions for the derivation of central aortic waveform
      characteristics in subjects with type 2 diabetes and cardiovascular disease.

PMID- 15451942
TI  - Use of arterial transfer functions for the derivation of central aortic waveform
      characteristics in subjects with type 2 diabetes and cardiovascular disease.

PMID- 15451944
TI  - Insulin detemir offers improved glycemic control compared with NPH insulin in
      people with type 1 diabetes.

PMID- 15451946
TI  - Global prevalence of diabetes: estimates for the year 2000 and projections for
      2030.

PMID- 15451948
TI  - Biological variation in HbA1c predicts risk of retinopathy and nephropathy in
      type 1 diabetes.

PMID- 15451950
TI  - The Supreme Court limits lawsuits against managed care organizations.
AB  - In Aetna Health Inc. v. Davila, the United States Supreme Court revisited the
      question of whether the Employee Retirement Income Security Act (ERISA) precludes
      state lawsuits against ERISA plans. The Court held that ERISA preempts damage
      actions brought against managed care organizations under the Texas Health Care
      Liability Act because ERISA itself provides the exclusive remedy for challenging
      ERISA plans' coverage decisions. The Court suggested, however, that health plans
      might be liable for treatment decisions made by employed physicians. It also
      volleyed back to Congress the question of whether ERISA beneficiaries should have
      any remedy for damages caused by coverage decisions.

PMID- 15451951
TI  - Generic dispensing and substitution in mail and retail pharmacies.
AB  - Mail-order pharmacies have lower aggregate generic-dispensing rates than their
      retail counterparts. This fact has been used as evidence of self-dealing that
      could arise when a pharmacy benefit manager (PBM) is both a plan administrator
      and a pharmacy owner. Using the aggregate generic-dispensing rate, however, is
      problematic because it confounds variation in performance with differences in
      demand. Controlling for therapeutic mix alone explains 87 percent of the apparent
      difference in aggregate dispensing rates. An alternative measure--one that fully
      controls for differences in price and indications across molecules within a
      category--eliminates the discrepancy in dispensing rates.

PMID- 15451952
TI  - Closing the doughnut hole: no easy answers.
AB  - The price differentials reported by Gerard Anderson and colleagues are not fully
      representative and are probably biased upward. If Congress does seek to reduce
      drug prices, there are no simple, effective, and efficient strategies. The most
      likely is drug importation, which would be ineffective at lowering U.S. drug
      costs and would pose sizable safety risks, yet it would reduce research and
      development (R&D) costs and access for foreign consumers. Careful cost
      effectiveness analysis would be more appropriate than trying to import other
      countries' price controls. Income-related subsidies are a better strategy for
      dealing with excessive cost sharing for low-income seniors.

PMID- 15451953
TI  - Doughnut holes and price controls.
AB  - In 2003 citizens of Canada, the United Kingdom, and France paid an average of 34
      59 percent of what Americans paid for a similar market basket of pharmaceuticals.
      If the Medicare program were to pay comparable prices for pharmaceuticals, it
      would be possible to eliminate the "doughnut hole" in its prescription drug
      benefit and keep Medicare drug spending within the overall limits established by
      Congress. This provides Congress with a clear choice: reduce the level of cost
      sharing and improve beneficiaries' access to pharmaceuticals, or allow the
      pharmaceutical industry to use the higher prices to fund research and development
      and to engage in other activities.

PMID- 15451954
TI  - Paying for health care in retirement: workers' knowledge of benefits and
      expenses.
AB  - Anecdotal evidence of retirees returning to the workforce to obtain health
      coverage has appeared against a backdrop of rising health insurance premiums and
      cutbacks in employer health benefit offerings to both current and future
      retirees. We present findings from a survey of workers ages forty-five to sixty
      four concerning their attitudes toward and plans for health care coverage and
      expenses during retirement. We find a mismatch between workers' expectations
      about the benefits that are likely to be available to them and their planning as
      to how they will pay for health care in retirement.

PMID- 15451955
TI  - Changes in medicaid physician fees, 1998-2003: implications for physician
      participation.
AB  - After slow growth during much of the 1990s, Medicaid physician fees increased, on
      average, by 27.4 percent between 1998 and 2003. Primary care fees grew the most.
      States with the lowest relative fees in 1998 increased their fees the most, but
      almost no states changed their position relative to other states or Medicare.
      Physicians in states with the lowest Medicaid fees were less willing to accept
      most or all new Medicaid patients in both 1998 and 2003. However, large fee
      increases were associated with primary care physicians' greater willingness to
      accept new Medicaid patients.

PMID- 15451956
TI  - Recent trends in state nursing home payment policies.
AB  - State Medicaid programs pay for a sizable portion of overall nursing home
      expenditures. The repeal of the Boren amendment in 1997 gave states greater
      freedom to set Medicaid nursing home policy. This study presents data from a
      comprehensive survey of state nursing home payment policies during 1999-2002.
      Aggregate inflation-adjusted Medicaid payment rates rose steadily, and there was
      no sizable increase in the adoption of other cost-cutting policies. Although
      these findings can be interpreted with some optimism from a nursing home
      financing perspective, areas of concern remain for state nursing home policy
      during the next several years.

PMID- 15451957
TI  - Tracking health care costs: trends turn downward in 2003.
AB  - Health care spending per privately insured person increased 7.4 percent in 2003.
      While lower than the 2002 increase, it still outpaced growth in the overall
      economy by a margin that exceeds the historical average. The trend for drug
      spending decelerated the most. Meanwhile, hospital spending grew 9 percent in
      2003-1.8 percentage points less than the 2002 increase. This reflected a sharp
      deceleration in growth of hospital use, while growth in hospital prices
      accelerated for the sixth year in a row. The trend for health insurance premiums
      fell in 2004. Employers raised patient cost sharing for the third year in a row.

PMID- 15451958
TI  - Local variation in public health preparedness: lessons from California.
AB  - Since September 2001 Congress has allocated approximately dollars 3 billion to
      strengthen the public health infrastructure. To achieve this goal, the U.S.
      Centers for Disease Control and Prevention (CDC) allocates funding to states,
      which distribute funds to local jurisdictions. Evidence-based measures to assess
      public health preparedness are lacking. We used an expert-panel process to
      develop performance measures, based on the ten essential public health services.
      We developed and conducted tabletop exercises in California to evaluate
      preparedness to detect and respond to a hypothetical smallpox outbreak based on
      those measures. There was wide variation of readiness in California. While the
      sources of variation are often different, common infrastructure gaps need to be
      addressed.

PMID- 15451959
TI  - The kindness of strangers: community effects on the rate of employer coverage.
AB  - The rate of employer-sponsored insurance (ESI) varies greatly across states. We
      analyze the factors that account for that variation. We find that the likelihood
      that a worker is covered by ESI depends on workers' own characteristics and also
      on those of other workers in the same metropolitan statistical area. Further, in
      almost all states the percentage of workers covered by ESI is close to the
      predicted level of coverage, which suggests that state policies that could affect
      insurance coverage have had little net effect on ESI rates. Hawaii is an
      exception: Its mandate on employers to offer coverage results in a rate of ESI
      that is much higher than expected.

PMID- 15451960
TI  - The role of standards in electronic prescribing.
AB  - The focus on preventing medical errors has advanced the arguments for widespread
      implementation of electronic prescribing. The choice of systems as well as the
      variation in functionality is large. Value and return on investment depend on the
      functionality provided. The paper by Douglas Bell and colleagues defines the
      functionalities that are required and desirable to ensure patient safety and
      quality of care. Health data standards are a prerequisite for the
      interoperability to support electronic prescribing. This paper discusses some of
      the barriers and problems in producing and adopting those standards.

PMID- 15451961
TI  - How to succeed in health information technology.
AB  - The United States is poised to move the debate over electronic information
      systems for health care beyond the question of whether to computerize to how to
      computerize. Developers should heed the experiences of those who have already
      attempted similar efforts in vertically integrated environments. A key lesson is
      that the expertise and design perspectives of IT professionals should be
      supplemented with practical input from the caregivers and administrators who will
      actually use these systems. The paper by Douglas Bell and colleagues offers a ray
      of hope, as these authors have begun their process by asking the user community
      exactly what it needs.

PMID- 15451962
TI  - Changes in health insurance coverage during the economic downturn: 2000-2002.
AB  - Using Current Population Survey data from 2000-2002, this paper documents the
      changes that led the uninsured population to grow by 3.8 million during that time
      period. All of the increase in the uninsured occurred among adults, and two
      thirds was among low-income adults. The extent to which the loss of employer
      coverage resulted in people becoming uninsured depended on their access to public
      programs: Children were more likely than adults to gain public coverage; women
      more likely than men; and parents more likely than nonparents. Middle- and higher
      income Americans were also affected because many lost income and because rates of
      employer coverage were lower.

PMID- 15451963
TI  - Translating ideals for health information technology into practice.
AB  - Standards for communication, content, function, and clinical knowledge are
      essential for electronic health records and e-prescribing, as well as other
      health information technologies. The current process for standard setting is
      competitive and voluntary, and it does not ensure that accepted standards will be
      incorporated into health information products. A three-tier architecture of
      development (research and validation), authorization (approval and
      dissemination), and certification (product evaluation) will make standards a core
      feature of future health information technology. Patient safety, health
      information technology uptake, and portability of data would all be enhanced by
      an orderly standard-diffusion process.

PMID- 15451964
TI  - Managed care rebound? Recent changes in health plans' cost containment
      strategies.
AB  - Large increases in health care costs combined with an economic slowdown have
      created pressures for health plans and employers to reconsider cost containment
      strategies that were scaled back after the managed care backlash. In this paper
      we examine how plans' approaches to cost containment and care management have
      evolved since 2001. Plans reintroduced and refocused some utilization management
      techniques during 2002 and 2003 while continuing to invest in disease and case
      management. Some also began to experiment with new variants of managed care,
      including tiered provider networks and incentive-based provider payments.
      However, few respondents believed that these strategies alone would greatly
      reduce future costs.

PMID- 15451967
TI  - The impact of drug coverage on COX-2 inhibitor use in Medicare.
AB  - Passage of the Medicare drug benefit legislation has renewed attention to the
      relationship between drug coverage and medication use. This study assesses the
      impact of drug coverage on COX-2 inhibitor use among elderly people with
      osteoarthritis, taking into account risk for adverse gastrointestinal events. COX
      2 use among aged beneficiaries with the most generous coverage was twice that of
      those with no third-party coverage. COX-2 use also increased with increasing
      gastrointestinal risk. However, this risk differential in COX-2 use disappears
      among those with the most generous coverage. Potential overuse of costly
      medications should be addressed as the Medicare drug benefit is being phased in.

PMID- 15451968
TI  - Large firms' retiree health benefits before Medicare reform: 2003 survey results.
AB  - This survey of large, private-sector employers offering retiree health benefits
      in 2003 provides a detailed baseline of private retiree health plans on the eve
      of the most sweeping changes to Medicare since its enactment. Total retiree
      health costs rose 13.7 percent in 2003, and average retiree contributions to
      premiums for employees age sixty-five and older retiring in 2003 rose 18 percent.
      Nearly half of surveyed employers have capped their contributions to health
      coverage for retirees over age sixty-five. Before passage of the new Medicare
      legislation, 20 percent said that they are likely to eliminate benefits for
      future retirees within three years.

PMID- 15451969
TI  - Health spending projections through 2013.
AB  - The rate of growth in national health expenditures is projected to fall to 7.8
      percent in 2003 because of slower private and public spending growth. However,
      during the next ten years health spending growth is expected to outpace economic
      growth. As a result, the health share of gross domestic product (GDP) is
      projected to increase from 14.9 percent in 2002 to 18.4 percent in 2013. The
      recently passed Medicare drug benefit legislation (not included in these
      projections) is not anticipated to have a large impact on overall national health
      spending, but it can be expected to cause sizable shifts in payment sources.

PMID- 15451970
TI  - Physicians and prepaid group practices.
AB  - Prepaid group practices (PGPs) are complex organizations that directly combine
      prepayment for health care with a comprehensive health care delivery system.
      PGPs' ability to manage their physician staffing efficiently must be placed in
      context with the cost and quality of their care. It seems unlikely that PGPs or
      their use of staff will proliferate. With increased integration of care through
      disease management programs and use of clinical information technology, it should
      be possible for the United States as a whole to come closer to achieving the care
      delivery goals that PGPs have set in the past.

PMID- 15451971
TI  - Benefits and pitfalls in applying the experience of prepaid group practices to
      the U.S. physician supply.
AB  - The paper by Jonathan Weiner includes important improvements in the methodology
      used to compare the physician workforce in prepaid group practices (PGPs) with
      the U.S. physician workforce. It also provides valuable insights for policymakers
      and researchers. Despite the improvements, concerns remain regarding the
      comparability of the populations served and physician activities in PGPs and the
      country as a whole. While PGPs appear to offer valuable lessons on how to use
      physicians effectively and efficiently, it is inappropriate to use the PGP
      physician rates to determine the number of physicians needed in the United
      States.

PMID- 15451972
TI  - My dad was not a prepaid group practice patient.
AB  - The author's father was a psychiatrist, a concerned citizen, and a Medicare
      patient. He died recently after a prolonged illness during which a panoply of
      physicians cared for him in ways that were sometimes redundant, inefficient, and
      poorly coordinated. He was definitively not a prepaid group practice patient. The
      author reviews the growing body of evidence that suggests that physician density
      is associated with greater costs but not improved outcomes. He reflects on his
      father's concerns with equity in health care and how prepaid managed care might
      have provided more efficient and less expensive medical coverage for his father's
      final sickness.

PMID- 15451973
TI  - Do we need more physicians?
AB  - A reexamination of physician productivity can resolve the current workforce
      debate. If the improvement of patients' health and well-being is the goal of
      medicine, then physician productivity should use this as the output instead of
      physician work effort (visits, procedures, or relative value units). Jonathan
      Weiner's study of prepaid group practices (PGPs) and regional data from the
      Dartmouth Atlas of Health Care demonstrate that the combination of low physician
      labor inputs with favorable outcomes is achievable in varied payer environments.
      Better medical care requires not more physicians, but rather improving physician
      productivity to the levels already present in many locales.

PMID- 15451974
TI  - Cardiology workforce: a shortage, not a surplus.
AB  - The United States faces a serious shortage of cardiologists as our population
      ages and the burden of heart disease grows. The problem is compounded by a
      cutback in the number of cardiology training positions a decade ago. Dramatic
      scientific, technological, and procedural advances fueled the growth of
      cardiology during the second half of the twentieth century. Patients benefited
      from access to specialists who transformed new knowledge into longer and better
      lives. Demand for cardiologists is strong and growing. An adequate supply of
      highly trained cardiologists is necessary to promote discovery and innovation and
      to help deliver state-of-the-art care to a growing number of cardiac patients.

PMID- 15451975
TI  - The changing shape of the physician workforce in prepaid group practice.
AB  - Multiple factors have combined to change the size and specialty composition of
      the physician workforce in the nation's largest prepaid group practices over the
      past two decades. An examination of these changes can shed some light on the past
      and potential future impact that changes in medical technology are likely to have
      on the physician workforce of these organizations and the greater physician
      community.

PMID- 15451976
TI  - Americans' views about the adequacy of health care for children and the elderly.
AB  - Recent attempts to increase health coverage for specific populations
      incrementally have been more successful than efforts to dramatically reconfigure
      the health care system. We present findings from a survey to assess support for
      programs for children compared with those for the elderly, as well as the
      public's desire to prioritize whether the needs of one should be addressed over
      the needs of the other. Americans believe that the health care needs of both
      children and the elderly are not being met, and there is clear and widespread
      support for a government role in ensuring adequate health care.

PMID- 15451977
TI  - Prepaid group practice staffing and U.S. physician supply: lessons for workforce
      policy.
AB  - This paper describes staffing at eight large prepaid group practices (PGPs)
      serving more than eight million enrollees at Kaiser Permanente and two other
      health maintenance organizations (HMOs). Even after characteristics of the
      patient populations and outside referrals are accounted for, these PGPs have a
      physician-to-population ratio that is 22-37 percent below the national rate. Two
      decades of historical data at Kaiser Permanente indicate that its rate of
      specialist growth was far higher than that of primary care. The study suggests
      that efficient systems of care can readily meet the demands of patient
      populations with workforce staffing ratios below current U.S. levels.

PMID- 15451978
TI  - Which medical conditions account for the rise in health care spending?
AB  - We calculate the level and growth in health care spending attributable to the
      fifteen most expensive medical conditions in 1987 and 2000. Growth in spending by
      medical condition is decomposed into changes attributable to rising cost per
      treated case, treated prevalence, and population growth. We find that a small
      number of conditions account for most of the growth in health care spending--the
      top five medical conditions accounted for 31 percent. For four of the conditions,
      a rise in treated prevalence, rather than rising treatment costs per case or
      population growth, accounted for most of the spending growth.

PMID- 15451979
TI  - Recommendations for comparing electronic prescribing systems: results of an
      expert consensus process.
AB  - Commercially available electronic prescribing systems may differ in their effects
      on patients' health outcomes and on patients' ability to manage costs. An expert
      panel convened to recommend specific features that would enable electronic
      prescribing systems to advance these goals. The panel authored sixty
      recommendations and rated each using a modified Delphi process. Ratings
      identified fifty-two recommendations as clearly positive for patient safety and
      health outcomes and forty-three recommendations as achievable in the average
      clinician's office within three years. Overall, these recommendations offer a
      synthesis of evidence and expert opinion that can help guide the development of
      electronic prescribing policy.

PMID- 15451980
TI  - Savings from drug discount cards: relief for Medicare beneficiaries?
AB  - Beginning in mid-2004, Medicare beneficiaries can enroll in prescription drug
      discount card programs approved by the federal government. We estimate modest
      savings for beneficiaries without drug coverage from existing drug discount card
      programs, with average savings of 17.4 percent over current retail prices.
      Although estimated percentage savings are greater on generics than brand-name
      drugs, estimated absolute dollar savings are greater for brands. Medicare
      approved discount card savings for individual beneficiaries will depend on
      current out-of-pocket drug spending, the number and types of drugs used, and
      specific card program features. Aggregate savings estimates vary widely, based on
      uncertainty in discounts and program participation rates.

PMID- 15451981
TI  - Medicare spending, the physician workforce, and beneficiaries' quality of care.
AB  - The quality of care received by Medicare beneficiaries varies across areas. We
      find that states with higher Medicare spending have lower-quality care. This
      negative relationship may be driven by the use of intensive, costly care that
      crowds out the use of more effective care. One mechanism for this trade-off may
      be the mix of the provider workforce: States with more general practitioners use
      more effective care and have lower spending, while those with more specialists
      have higher costs and lower quality. Improving the quality of beneficiaries' care
      could be accomplished with more effective use of existing dollars.

PMID- 15451982
TI  - The Institute of Medicine committee's clarion call for universal coverage.
AB  - The Institute of Medicine (IOM) Committee on the Consequences of Being Uninsured
      is to be commended for its work, which recently culminated in the release of six
      volumes on the subject. The concluding volume presents a vision for universal
      coverage and describes four options for achieving it. The options include an
      incremental approach, employer and individual mandates, and a single-payer plan.
      We identify complications involving benefits and geographic variation in costs
      surrounding attempts to achieve universal coverage. The complications suggest
      that the committee's cost estimates may be too low and that there may be sizable
      political barriers to the proposals.

PMID- 15451983
TI  - How federalism could spur bipartisan action on the uninsured.
AB  - National efforts to greatly reduce the number of uninsured Americans have made
      little progress for decades because achieving majority support for any one
      approach has proved to be impossible. While as authors we remain unreconciled on
      the best solution, we share the belief that federally supported state
      experimentation is a promising way to make progress. States should be allowed to
      try widely differing solutions with federal financial support under legislated
      guidelines, including specific protections and measurable goals. Congress would
      enact a "policy toolbox" of federal initiatives that states could include, and
      funding to states would be linked to success in reaching the goals.

PMID- 15451984
TI  - Covering the uninsured: what is it worth?
AB  - One out of six Americans under age sixty-five lacks health insurance, a situation
      that imposes sizable hidden costs upon society. The poorer health and shorter
      lives of those without coverage account for most of these costs. Other impacts
      are manifested by Medicare and disability support payments, demands on the public
      health infrastructure, and losses of local health service capacity. We conclude
      that the estimated value of health forgone each year because of uninsurance
      (dollars 65-dollars 130 billion) constitutes a lower-bound estimate of economic
      losses resulting from the present level of uninsurance nationally.

PMID- 15451985
TI  - Hospital emergency departments: the authors respond.
AB  - In response to a perceived crisis in California's emergency department (ED)
      capacity, Glenn Melnick and colleagues sought to construct an empirical database
      that could bring objective data to bear on this important issue. In this response
      they address some of the substantive issues raised by the authors of four
      preceding commentaries. These issues include the use of aggregates and averages,
      the omission of trauma centers, staffing shortages, and overcrowding. In their
      view, the paper has added reliable new information to better understand the
      underlying economics faced by community hospitals with EDs and how they have
      responded over the past decade.

PMID- 15451986
TI  - Emergency capacity in California: a look at more recent trends.
AB  - The dynamic environment in California is changing the world of hospitals at an
      increasing pace. The paper by Glenn Melnick and colleagues concludes that there
      is a "robust market" for emergency department (ED) services in California. The
      paper's economic conclusions are drawn from averages and unverified assumptions
      about ED patients who are admitted as inpatients. In addition to the limitations
      imposed by evaluating only capacity, the study did not acknowledge or take into
      account new ED nurse-to-patient ratios, sky-rocketing costs of on-call
      physicians, seismic compliance costs, technology, or a host of other separate but
      vital variables that must be evaluated and integrated.

PMID- 15451987
TI  - Emergency care in California: no emergency?
AB  - Glenn Melnick and colleagues' analysis of emergency department (ED) capacity and
      access in California is fatally flawed because the authors do not consider the
      operational constraints that severely compromise ED functioning. Simple counts of
      ED beds and distance to the closest hospital ED are virtually meaningless without
      considering, for example, the operational impact of loss of inpatient bed
      capacity, the nurse shortage, declining availability of on-call specialists, lack
      of access to primary care, and growing numbers of uninsured people. Other surveys
      indicate that ED overcrowding and ambulance diversion are serious and growing
      problems-not only in California, but nationwide.

PMID- 15451988
TI  - The emergency department: rethinking the safety net for the safety net.
AB  - America's emergency departments (EDs) are in crisis. The dwindling numbers of EDs
      are increasingly overcrowded as they cope with rising demand. In a Health Affairs
      Web Exclusive, Glenn Melnick and his colleagues find that despite these trends,
      overall ED capacity is actually increasing in California. While this may appear
      to make financial sense for some hospitals, it is a costly response that does
      little to fix the complex problems that drive ED overcrowding. Given a
      convergence of factors, it may now be time to radically alter and broaden our
      historical expectations of the role of the ED.

PMID- 15451989
TI  - Emergency care in California: robust capacity or busted access?
AB  - Licensed emergency department (ED) capacity is a static measure that is
      inadequate to evaluate a system that the public and policymakers expect to
      respond dynamically to individual patients in a timely manner. Government
      mandates on hospital-based providers, undersupply of trained and willing
      personnel, and private market imperatives all curtail the functional capacity of
      the emergency care system. Although most Californians still live within a few
      miles of the closest hospital, many ambulance patients are diverted much further
      because of ED crowding. Many ambulatory patients are delayed so long in waiting
      rooms that they return home without ever being seen.

PMID- 15451990
TI  - Emergency department capacity and access in California, 1990-2001: an economic
      analysis.
AB  - Media report that hospitals are closing their emergency departments (EDs) and
      reducing access to ED services, raising concerns that EDs are not sustainable
      under competition and managed care. We analyzed financial, economic, capacity,
      and utilization data for California EDs for 1990-2001. We found that contrary to
      media reports, hospitals are not abandoning the ED market. Rather, our results
      show a robust market, where hospitals are adding ED capacity to meet increased
      demand and to maintain access. Supporting economic analyses show that EDs are
      sustainable since they generate a sizable and growing portion of inpatient
      admissions, which contribute to overall economic viability.

PMID- 15451991
TI  - Workers' perspectives on mandated employer health insurance.
AB  - There is renewed discussion of using employer mandates as a strategy for
      decreasing the number of uninsured Americans. California recently passed the
      Health Insurance Act of 2003, the first state-based "play-or-pay" legislation in
      nearly a decade. To better understand workers' perceptions, the California
      HealthCare Foundation commissioned NORC at the University of Chicago to conduct a
      survey to assess workers' views on mandated employer coverage. We found that the
      vast majority of workers support such a mandate--regardless of whether they are
      insured--although there is some variation regarding how extensive the mandate
      should be.

PMID- 15451992
TI  - The effect of tax credits for nongroup insurance on health spending by the
      uninsured.
AB  - We compare out-of-pocket spending for health care by lower-income uninsured
      people with their net spending on insurance and health care if they took up each
      of three hypothetical tax credits. Because of nongroup policies' high cost and
      low benefits, nearly all would spend more, often much more, under a tax credit
      similar to that proposed by the Bush administration. When viewed in the context
      of other research on low-income people's demand for health insurance, the results
      suggest that sizable reductions in the number of uninsured will require more
      generous tax credits than those in current proposals.

PMID- 15451993
TI  - The cost of tax-exempt health benefits in 2004.
AB  - The tax expenditure for health benefits is the amount of revenues that the
      federal government forgoes by exempting health benefits and spending from the
      federal income and Social Security taxes, including (1) employer health benefit
      contributions for workers and retirees, (2) health benefit deductions for the
      self-employed, (3) health spending under flexible spending plans, and (4) the tax
      deduction for health expenses. We estimate that this expenditure will be dollars
      188.5 billion in 2004. Families with incomes of dollars 100,000 or more (14
      percent of the population) account for 26.7 percent of all health benefit tax
      expenditures.

PMID- 15451994
TI  - Twenty-seven fingers without a palm is not a hand: a conversation with Elias
      Zerhouni.
AB  - The director of the National Institutes of Health, Elias Zerhouni, looks back on
      his first eighteen months at the helm of the NIH. During his tenure, appointed by
      a Republican president but himself a political Independent, Zerhouni has been
      called upon to navigate the treacherous waters where science meets politics. His
      efforts have been assisted by a new Roadmap supplemented by the recommendations
      of the Institute of Medicine, regarding the organization and priorities of the
      NIH. Priorities include continuing to work on infectious and chronic diseases,
      both at home and abroad, and focusing the efforts of twenty-seven separate
      institutes under one director and a common organizational mission.

PMID- 15451995
TI  - Setting priorities in medical care through benefit design and medical management.
AB  - As health care costs continue to increase, so does the importance of setting
      priorities in the allocation of medical care resources. Based on a November 2003
      roundtable, this paper discusses the potential for benefit design (the definition
      of covered benefits) and medical management (the criteria by which benefits are
      applied to specific patients) to contribute to priority setting, particularly in
      the context of increasing emphasis on evidence-based medicine.

PMID- 15451996
TI  - Cost-effectiveness: will the public buy it or balk?
AB  - The prospect of cost-effectiveness as a criterion for treatment or coverage
      decisions may be met with stiff resistance from the public. A characteristically
      American reverence for new technology and abhorrence at putting a price on life
      conflict with the premise of value-based decisions. Nevertheless, if particular
      checks and balances are incorporated, consumer acceptance is possible. Since
      health care leaders deny that cost plays a role in coverage decisions, it may be
      time for a more realistic and open public debate on how to incorporate cost to
      achieve an optimal allocation of resources.

PMID- 15451997
TI  - Cost-effectiveness and evidence evaluation as criteria for coverage policy.
AB  - Private health plans and government health insurance programs in the United
      States base their coverage decisions on evidence criteria, rather than explicit
      cost-effectiveness criteria. As health spending continues to grow rapidly,
      however, approaches to coverage policy that ignore costs fail to meet the needs
      of consumers, employers, health plans, and federal and state governments. I
      describe the role of evidence-based criteria in formal coverage decision making
      and contrast the ways that these criteria differ from cost-effectiveness
      criteria. Finally, I discuss options for incorporating considerations of cost
      effectiveness into coverage policy and other aspects of benefit design.

PMID- 15451998
TI  - Integrating disease management into the outpatient delivery system during and
      after managed care.
AB  - Managed care introduced disease management as a replacement strategy to
      utilization management. The focus changed from influencing treatment decisions to
      supporting self-care and compliance. Disease management rendered operational many
      elements of the chronic care model, but it did so outside the delivery system,
      thus escaping the financial limitations, cultural barriers, and inertia inherent
      in effecting radical change from within. Medical management "after managed care"
      should include the functional and structural integration of disease management
      with primary care clinics. Such integration would supply the infrastructure that
      primary care physicians need to coordinate the care of chronically ill patients
      more effectively.

PMID- 15451999
TI  - Medical management after managed care.
AB  - Health insurers are under conflicting pressures to improve the quality and
      moderate the costs of health care yet to refrain from interfering with decision
      making by physicians and patients. This paper examines the contemporary evolution
      of medical management, drawing on examples from UnitedHealth Group, WellPoint
      Health Networks, and Active Health Management. It highlights the role of claims
      data, predictive modeling, notification requirements, and online enrollee self
      assessments; the choice between focusing on behavior change among patients or
      among physicians; and the manner in which medical management is packaged and
      priced to accommodate the diversity in willingness to pay for quality initiatives
      in health care.

PMID- 15452000
TI  - Advocating for medical diplomacy: a conversation with Tommy G. Thompson.
AB  - Health Affairs founding editor John Iglehart interviews HHS Secretary Tommy
      Thompson, who calls for closer integration of health policy and foreign policy,
      with the aim of improving the lives of vulnerable populations and serving the
      best interests of the United States. Thompson also discusses the indelible
      impressions of his travels to Afghanistan, Africa, and Iraq; the Medicare drug
      discount card program; and more.

PMID- 15452001
TI  - Turning point or tipping point: new FDA draft guidances and the future of DTC
      advertising.
AB  - According to Food and Drug Administration (FDA) research, direct-to-consumer
      (DTC) drug ads are not as empowering as they were even three years ago. How will
      the FDA's new draft guidances reverse this trend and affect the future of DTC
      advertising? Will they be a turning point, resulting in pharmaceutical companies'
      embracing an educational public health imperative, or a tipping point with
      politicians and the public zeroing in on aggressively targeted DTC ads as the
      postimportation pharmaceutical bete noire? The FDA believes that its new
      guidances strengthen the strategic argument that a better-informed consumer lays
      the groundwork for a better potential customer.

PMID- 15452002
TI  - Ensuring that consumers receive appropriate information from drug ads: what is
      the FDA's role?
AB  - The promise of direct-to-consumer (DTC) prescription drug advertisements lies in
      their potential to educate consumers about medical conditions and the possibility
      of treatment. But this promise can only be fulfilled if consumers are given clear
      and accurate information. The responsibility for ensuring that this occurs falls
      on the Food and Drug Administration (FDA). Recent congressional investigations
      have indicated that the agency is failing at this task, as FDA enforcement
      actions against false and misleading ads have declined precipitously in recent
      years. Other FDA efforts, such as its recently released guidelines on
      prescription drugs, do not appear to be helpful, potentially confusing consumers
      more than helping them.

PMID- 15452003
TI  - Direct-to-consumer drug advertising: you get what you pay for.
AB  - Between 1997 and 2001 spending on direct-to-consumer (DTC) drug advertising more
      than doubled. Opinions differ as to whether and to what extent DTC advertising
      benefits the doctor-patient relationship. Some analysts argue that the current
      regulatory regime is sufficient, others advocate a stricter enforcement, and
      still others promote an outright ban. An alternative may be to use the purchasing
      power of the federal government to require the inclusion of comparative quality
      data, thus creating a basis for more informed consumer choice. This approach
      could create incentives for the pharmaceutical industry to adjust spending on DTC
      advertising while avoiding "big government" interference with commercial free
      speech.

PMID- 15452004
TI  - Direct-to-consumer advertising: developing evidence-based policy to improve
      retention and comprehension.
AB  - Pharmaceutical advertising was historically directed toward health care
      professionals and mainly communicated through medical journals. The arrival of
      direct-to-consumer advertising has sparked both praise and criticism. Although
      current Food and Drug Administration requirements for drug promotion were written
      from a health care professional perspective, the same regulations have been
      applied to advertising directed at consumers. This has led to questions regarding
      the appropriate method for communicating detailed medical information. Rigorous
      research is needed to evaluate and determine the most effective format for
      communicating benefit and risk information to consumers. New standards for drug
      advertising to consumers should be grounded in data derived from this type of
      research.

PMID- 15452005
TI  - DTC advertising's benefits far outweigh its imperfections.
AB  - Direct-to-consumer (DTC) communication about pharmaceutical products enables
      consumers to take a hands-on interest in their own health care. A growing body of
      research and expert opinion supports the view that the information presented in
      DTC communications informs patients' decision making and leads to more productive
      physician/patient encounters. Arguments that DTC advertising leads doctors to
      write unnecessary prescriptions and increases costs are unfounded. Criticism of
      the practice may also be shortsighted, because outpatient drug treatment can
      substitute for more costly therapies and hospitalizations. Public debate should
      focus on making information clear and comprehensible so that consumers can get
      maximum value.

PMID- 15452006
TI  - The value of benefit data in direct-to-consumer drug ads.
AB  - Direct-to-consumer (DTC) pharmaceutical ads typically describe drug benefits in
      qualitative terms; they rarely provide data on how well the drug works. We
      describe an evaluation of a "prescription drug benefit box"-data from the main
      randomized trials on the chances of various outcomes with and without the drug.
      Most participants rated the information as "very important" or "important";
      almost all found the data easy to understand. Perceptions of drug effectiveness
      were much lower for ads that incorporated the benefit box than for ads that did
      not. Most people we interviewed want benefit data in drug ads, can understand
      these data, and are influenced by them.

PMID- 15452007
TI  - Physicians report on patient encounters involving direct-to-consumer advertising.
AB  - We surveyed a national sample of 643 physicians on events associated with visits
      during which patients discussed an advertised drug. Physicians perceived improved
      communication and education but also thought that direct-to-consumer advertising
      (DTCA) led patients to seek unnecessary treatments. Physicians prescribed the
      advertised drug in 39 percent of DTCA visits but also recommended lifestyle
      changes and suggested other treatments. Referring to visits when the DTCA drug
      was prescribed, 46 percent said that it was the most effective drug, and 48
      percent said that others were equally effective. Prescribing DTCA drugs when
      other effective drugs are available warrants further study.

PMID- 15452008
TI  - Employers' contradictory views about consumer-driven health care: results from a
      national survey.
AB  - Based on a random national sample of 1,856 employers, this paper examines
      employers' knowledge, perceptions, and present and future plan offerings for
      consumer-driven health care plans. Employers of all sizes are more familiar with
      consumer-driven health care than with organizations that promote quality of care.
      Many employers remain skeptical about its ability to control costs and improve
      quality, while a majority believe that health reimbursement arrangements (HRAs)
      are likely to attract healthier workers. Interest in HRAs is greatest among the
      largest U.S. employers. The percentage of covered workers who can choose an HRA
      plan should grow dramatically during the next two years.

PMID- 15452009
TI  - The medical malpractice 'crisis': recent trends and the impact of state tort
      reforms.
AB  - By many accounts, the United States is in the midst of its third medical
      malpractice "crisis." Physicians in several states are facing high and rising
      premiums. The largest national medical malpractice carrier and some large
      multistate physician-backed liability firms have recently left the market. Rising
      premiums are traced largely to increases in claims severity. Capping malpractice
      payments has been advanced as one approach to slowing the growth in premiums.
      This analysis finds that premiums in states that cap awards are 17.1 percent
      lower than in states that don't cap. At issue, however, is whether these stopgap
      solutions promote the goals of the U.S. liability system.

PMID- 15452010
TI  - Improving health systems and enhancing reproductive health: linkages and lessons
      for action.

PMID- 15452011
TI  - Strategies for engaging the private sector in sexual and reproductive health: how
      effective are they?
AB  - The private health sector provides a significant portion of sexual and
      reproductive health (SRH) services in developing countries. Yet little is known
      about which strategies for intervening with private providers can improve quality
      or coverage of services. We conducted a systematic review of the literature
      through PubMed from 1980 to 2003 to assess the effectiveness of private sector
      strategies for SRH services in developing countries. The strategies examined were
      regulating, contracting, financing, franchising, social marketing, training and
      collaborating. Over 700 studies were examined, though most were descriptive
      papers, with only 71 meeting our inclusion criteria of having a private sector
      strategy for one or more SRH services and the measurement of an outcome in the
      provider or the beneficiary. Nearly all studies (96%) had at least one positive
      association between SRH and the private sector strategy. About three-quarters of
      the studies involved training private providers, though combinations of
      strategies tended to give better results. Maternity services were most commonly
      addressed (55% of studies), followed by prevention and treatment of sexually
      transmitted diseases (32%). Using study design to rate the strength of evidence,
      we found that the evidence about effectiveness of private sector strategies on
      SRH services is weak. Most studies did not use comparison groups, or they relied
      on cross-sectional designs. Nearly all studies examined short-term effects,
      largely measuring changes in providers rather than changes in health status or
      other effects on beneficiaries. Five studies with more robust designs (randomized
      controlled trials) demonstrated that contraceptive use could be increased through
      supporting private providers, and showed cases where the knowledge and practices
      of private providers could be improved through training, regulation and
      incentives. Although tools to work with the private sector offer considerable
      promise, without stronger research designs, key questions regarding their
      feasibility and impact remain unanswered.

PMID- 15452012
TI  - Family planning and sexual health organizations: management lessons for health
      system reform.
AB  - Advocates of health system reform are calling for, among other things,
      decentralized, autonomous managerial and financial control, use of contracting
      and incentives, and a greater reliance on market mechanisms in the delivery of
      health services. The family planning and sexual health (FP&SH) sector already has
      experience of these. In this paper, we set forth three typical means of service
      provision within the FP&SH sector since the mid-1900s: independent not-for-profit
      providers, vertical government programmes and social marketing programmes. In
      each case, we present the context within which the service delivery mechanism
      evolved, the management techniques that characterize it and the lessons learned
      in FP&SH that are applicable to the wider debate about improving health sector
      management. We conclude that the FP&SH sector can provide both positive and
      negative lessons in the areas of autonomous management, use of incentives to
      providers and acceptors, balancing of centralization against decentralization,
      and employing private sector marketing and distribution techniques for delivering
      health services. This experience has not been adequately acknowledged in the
      debates about how to improve the quality and quantity of health services for the
      poor in developing countries. Health sector reform advocates and FP&SH advocates
      should collaborate within countries and regions to apply these management
      lessons.

PMID- 15452013
TI  - Designing a reproductive health services package in the universal health
      insurance scheme in Thailand: match and mismatch of need, demand and supply.
AB  - In October 2001 Thailand introduced universal healthcare coverage (UC) financed
      by general tax revenue. This paper aims to assess the design and content of the
      UC benefit package, focusing on the part of the package concerned with sexual and
      reproductive health (SRH). The economic concept of need, demand and supply in the
      process of developing the SRH package was applied to the analysis. The analysis
      indicated that SRH constitutes a major part of the package, including the control
      of communicable and non-communicable diseases, the promotion and maintenance of
      reproductive health, and early detection and management of reproductive health
      problems. In addition, the authors identified seven areas within three
      overlapping spheres; namely need, demand and supply. The burden of disease on
      reproductive conditions was used as a proxy indicator of health needs in the
      population; the findings of a study of private obstetric practice in public
      hospitals as a proxy of patients' demands; and the SRH services offered in the UC
      package as a proxy of general healthcare supply. The authors recommend that in
      order to ensure that healthcare needs match consumer demand, the inclusion of SRH
      services not currently offered in the package (e.g. treatment of HIV infection,
      abortion services) should be considered, if additional resources can be made
      available. Where health needs exist but consumers do not express demand, and the
      appropriate SRH services would provide external benefits to society (e.g. the
      programme for prevention of sexual and gender-related violence), policymakers are
      encouraged to expand and offer these services. Efforts should be made to create
      consumer awareness and stimulate demand. Research can play an important role in
      identifying the services in which supply matches demand but does not necessarily
      reflect the health needs of the population (e.g. unnecessary investigations and
      prescriptions). Where only demand or supply exists (e.g. breast cosmetic
      procedures and unproven effective interventions), these SRH services should be
      excluded from the package and left to private financing and providers, the
      government playing a regulatory role.

PMID- 15452014
TI  - Health sector reform and reproductive health services in poor rural China.
AB  - This paper describes and analyses the major reforms and changes that have
      occurred in the rural health sector of China. Key findings from a number of
      empirical studies on reproductive health service provision and utilization are
      summarized in order to assess the implications for reproductive health services
      of the ongoing health reform. The focus of this paper is what has actually been
      happening at the ground level, rather than what should have been happening as
      stated by rural health sector reform policies. It is argued that reproductive
      health is a missing component of the current health sector reform agenda. It also
      argued that the rural health sector reform in China is really a passive response
      to the changed rural socio-economic conditions rather than an active action aimed
      at improving the health status of the rural population. The ongoing rural health
      reform has produced both negative and positive implications for reproductive
      health services and there is a need for both the state, and for women, to play a
      much stronger role in this reform. Further studies and actions are required,
      however, to identify the specific type of roles and activities that the state and
      women need to undertake so as to fulfil the reproductive health goals and
      objectives set forth by the 1994 International Conference on Population and
      Development.

PMID- 15452015
TI  - Sexual and reproductive health: challenges for priority-setting in Ghana's health
      reforms.
AB  - Many countries are undertaking widespread structural change of their health
      sectors. There is mounting concern that priority-setting mechanisms used in
      planning the reforms are not suited to recognizing or taking account of the needs
      and priorities of sexual and reproductive health (SRH) services. The main aim of
      this research was to assess the sensitivity of the priority-setting tools and
      mechanisms used in the development of the health sector reforms in Ghana, to the
      needs and priorities of SRH services, and to consider how priority-setting
      mechanisms could be improved. We conclude that priority-setting tools in Ghana's
      reform process were rudimentary, and SRH donors and advocates were little
      involved. While it is tempting for a strong programme like Ghana's SRH programme
      to remain independent, we argue that closer involvement in system-wide reforms is
      a preferable long-term objective. Clearly, SRH priorities need safeguarding
      within a systems approach and we suggest a number of ways in which this can be
      achieved. Most importantly, the SRH community, in collaboration with the wider
      development community, needs to challenge current priority-setting mechanisms and
      the long-held view that traditional disease-ranking and cost-effectiveness
      measures are necessarily the best, most accurate way to measure health
      priorities. Traditional priority-setting tools do not adequately reflect the long
      term benefits of preventive interventions such as family planning, and are
      therefore not an adequate reflection of holistic health sector planning needs. In
      response to this, there needs to be greater commitment from the international
      development and research communities to: (1) support collaboration between
      economists and reproductive health specialists to develop better measures for the
      effectiveness and impact of SRH services; and (2) in the interim, accept proxies
      for priority-setting which may include small-scale, qualitative research data
      combined with priorities identified by SRH specialists. To achieve this, the
      priority-setting processes need to become more inclusive and SRH specialists need
      to be proactive in their engagement with health sector decision-makers.

PMID- 15452016
TI  - HIV/AIDS, sexual and reproductive health: intersections and implications for
      national programmes.
AB  - HIV and AIDS have a myriad of effects on sexual and reproductive health and
      rights, and sexual and reproductive health services are critical for women and
      men with HIV and AIDS. Yet there has been a dearth of visible, in-depth
      mainstream attention to the links between sexual and reproductive health and
      prevention and treatment of HIV/AIDS since the early 1990s among major
      stakeholders internationally. This paper argues that access to essential sexual
      and reproductive health care should be provided in HIV/AIDS prevention, care and
      treatment programmes, and appropriate forms of prevention and treatment of
      HIV/AIDS should be included in all sexual and reproductive health services as a
      public health priority, particularly in sex education, family planning and
      abortion services, pregnancy-related care, sexually transmitted infection (STI)
      services and services addressing sexual violence. The paper analyzes existing
      barriers to linking and integrating these services, e.g. at country level due to
      the traditional training of health workers to implement vertical programmes,
      separate sources of funding for National AIDS Control Programmes and sexual and
      reproductive health services, and in international donor programme and UN agency
      structures. This paper calls for leadership to be exercised by donors, all the UN
      agencies working together, governments, health service managers and providers,
      NGOs and advocates in both fields to develop and implement these linkages at
      country level. Finally, it is crucial that UNAIDS, WHO, UNFPA, UNICEF, the Global
      Fund to Fight AIDS, TB and Malaria and those working to reach the targets set by
      the Millennium Development Goals come on board in these efforts.

PMID- 15452017
TI  - 'It makes me want to run away to Saudi Arabia': management and implementation
      challenges for public financing reforms from a maternity ward perspective.
AB  - Poor practice by health care workers has been identified as contributing to high
      levels of maternal mortality in South Africa. The country is undergoing
      substantial structural and financial reforms, yet the impact of these on health
      care workers performance and practice has not been studied. This study, which
      consisted of an ethnography of two labour wards (one rural and one urban), aimed
      to look at the factors that shaped everyday practice of midwives working in
      district hospitals in South Africa during the implementation of a public sector
      reform to improve financial management. The study found that the Public Financing
      Management Act, that aimed to improve the efficiency and accountability of public
      finance management, had the unintended consequence of causing the quality of
      maternal health services to deteriorate in the hospital wards studied. The
      article supports the need for increased dialogue between those working in the
      sexual and reproductive health and health systems policy arenas, and the
      importance of giving a voice to front-line health workers who implement systems
      changes. However, it cautions that there are no simple answers to how health
      systems should be organized in order to better provide sexual and reproductive
      health services, and suggests instead that more attention in the debate needs to
      be paid to the challenges of policy implementation and the socio-political
      context and process issues which affect the success or failure of the
      implementation.

PMID- 15452018
TI  - Service accountability and community participation in the context of health
      sector reforms in Asia: implications for sexual and reproductive health services.
AB  - This paper examines the concept and practice of community participation in World
      Bank-supported health sector reforms in Asia, and how far such participation has
      strengthened accountability with regard to provision of sexual and reproductive
      health (SRH) services. It argues that the envisaged scope of community
      participation within a majority of reforms in Asia has been limited to programme
      management and service delivery, and it is occurring within the boundaries of
      priorities that are defined through non-participatory processes. Setting up of
      community health structures, decentralization and community financing are three
      important strategies used for promoting participation and accountability within
      reforms. The scant evidence on the impact of these strategies suggests that
      marginalized groups and sexual and reproductive rights based groups are poorly
      represented in the forums for participation, and that hierarchies of power
      between and amongst health personnel and the public play out in these forums.
      Community financing has not lead to enhanced service accountability. As a result
      of the above limitations, community participation in health sector reforms has
      rarely strengthened accountability with respect to provision of comprehensive SRH
      services. In this context, rights (including sexual and reproductive) based
      groups and researchers need to engage with design, monitoring and evaluation of
      health sector reforms, both from inside as participants and outside as pressure
      groups. Participation contracts enhancing powers of civil society
      representatives, quotas for participation (for women, other marginalized groups
      and rights-based organizations), and investment in capacity building of these
      stakeholders on leadership and sexual reproductive rights and health are pre
      requisites if participation is to lead to health and SRH service accountability.
      Community participation and service accountability hence requires more and not
      less investment of resources by the state.

PMID- 15452019
TI  - Measuring unmet obstetric need at district level: how an epidemiological tool can
      affect health service organization and delivery.
AB  - A national retrospective survey on the unmet need for major obstetric surgery
      using the Unmet Obstetric Need Approach was carried out in Mali in 1999. In
      Koutiala, the district health team decided to carry on the monitoring of the met
      need for several years in order to assess their progress over time. The first
      prospective study, for 1999, estimated that more than 100 women in need of
      obstetric care never reached the hospital and probably died as a consequence.
      This surprising result shocked the district health team and the resulting
      increased awareness of service deficits triggered operational measures to tackle
      the problem. The Unmet Obstetric Need study in Koutiala district was implemented
      without financial support and only limited external technical back-up. The
      appropriation of the study by the district team for solving local problems of
      access to obstetric care may have contributed to the success of the experience.
      Used as a health service management tool, the study and its results started a
      dialogue between the hospital staff and both health centre staff and community
      representatives. This had not only the effect of triggering consideration of
      coverage, but also of quality of obstetric care.

PMID- 15452020
TI  - LPS-binding protein-deficient mice have an impaired defense against Gram-negative
      but not Gram-positive pneumonia.
AB  - LPS-binding protein (LBP) can facilitate the transfer of cell wall components of
      both Gram-negative bacteria (LPS) and Gram-positive bacteria (lipoteichoic acid)
      to inflammatory cells. Although LBP is predominantly produced in the liver,
      recent studies have indicated that this protein is also synthesized locally in
      the lung by epithelial cells. To determine the role of LBP in the immune response
      to pneumonia, LBP gene-deficient (-/-) and normal wild-type (WT) mice were intra
      nasally infected with either Streptococcus pneumoniae or Klebsiella pneumoniae,
      common Gram-positive and Gram-negative pathogens, respectively. Pneumococcal
      pneumonia was associated with a 7-fold rise in LBP concentrations in
      bronchoalveolar lavage fluid of WT mice; LBP-/- mice infected with S. pneumoniae
      showed a similar survival and a similar bacterial burden in their lungs 48 h post
      infection. In Klebsiella pneumonia, however, LBP-/- mice demonstrated a
      diminished survival together with an enhanced bacterial outgrowth in their lungs.
      These data suggest that LBP is important for a protective immune response in
      Klebsiella pneumonia, but does not contribute to an effective host response in
      pneumococcal pneumonia.

PMID- 15452022
TI  - Is it essential to change the term "essential hypertension"?

PMID- 15452021
TI  - Functional T cells in primary immune response to histoplasmosis.
AB  - Functional T cells are critical to host defense against infection. It has been
      reported that functional T cells as determined by their cytokine production
      represent antigen-specific T cells in infectious disease models. In this study,
      we enumerated Histoplasma-specific interferon gamma-producing cells in bulk
      splenocyte culture and showed that infection with Histoplasma capsulatum, an
      intracellular pathogen of the macrophage, activated both CD4 and CD8 T cells. The
      magnitude of CD8 T cell response was lower than CD4 T cell, but the expansion and
      contraction of both cell types followed the same kinetics. Over 90% of interferon
      gamma-producing CD4 T cells and >85% of CD8 T cells expressed CD44(hi) phenotype.
      The strong correlation between interferon gamma production and CD44(hi)
      expression was observed not only at the peak of response but also throughout the
      course of infection. Moreover, a broad spectrum of Vbeta populations responded to
      systemic as well as pulmonary infections, suggesting no obvious T cell receptor
      bias in primary immune response to histoplasmosis. While each Vbeta population
      contributed to interferon gamma production, several specific Vbeta populations
      made up higher percentages of interferon gamma-producing cells. Our study laid
      the groundwork for further investigations in immune response to histoplasmosis.

PMID- 15452023
TI  - Omega-3 fatty acid supplementation augments sympathetic nerve activity responses
      to physiological stressors in humans.
AB  - An inverse relation exists between omega-3 fatty acid intake and risk of
      cardiovascular disease development/mortality and sudden cardiac death in humans.
      Mechanisms underlying this cardioprotective effect are unknown, but could involve
      the autonomic nervous system. We tested the hypothesis that omega-3 fatty acid
      supplementation ("fish oil") would reduce muscle sympathetic nerve activity
      (MSNA) at rest and attenuate increases during physiological stressors. MSNA
      (peroneal microneurography) was measured during rest, ischemic handgrip to
      fatigue (IHG), and a cold pressor test (CPT). Measurements were obtained before
      (PRE) and after (POST) 1 month of daily ingestion of either fish oil
      (experimental group, n=9) or olive oil capsules (control group, n=9). MSNA at
      rest was comparable PRE and POST in control (3+/-1 versus 3+/-1 bursts/30
      seconds) and experimental (4+/-1 versus 5+/-1 bursts/30 seconds) subjects. IHG
      and CPT increased MSNA in both groups PRE and POST. MSNA, arterial blood
      pressure, and heart rate responses to the stressors were similar PRE and POST in
      the control group. In contrast, MSNA responses to IHG (Delta4+/-2 and Delta9+/-2
      bursts/30 seconds; P<0.05 for PRE and POST, respectively) and CPT (Delta4+/-1
      versus Delta10+/-2 bursts/30 seconds; P<0.05) were augmented after omega-3 fatty
      acid supplementation whereas arterial blood pressure and heart rate responses
      were unchanged. These data indicate that 1 month of omega-3 fatty acid
      supplementation does not change MSNA at rest but augments sympathetic outflow to
      physiological stressors. The mechanism underlying augmented MSNA responses to
      physiological stressors after omega-3 fatty acid supplementation is unknown, but
      may involve impaired peripheral vasoconstriction.

PMID- 15452024
TI  - Pathophysiology of hypertensive renal damage: implications for therapy.
AB  - Unlike the majority of patients with uncomplicated hypertension in whom minimal
      renal damage develops in the absence of severe blood pressure (BP) elevations,
      patients with diabetic and nondiabetic chronic kidney disease (CKD) exhibit an
      increased vulnerability to even moderate BP elevations. Investigations in
      experimental animal models have revealed that this enhanced susceptibility is a
      consequence of an impairment of the renal autoregulatory mechanisms that normally
      attenuate the transmission of elevated systemic pressures to the glomeruli in
      uncomplicated hypertension. The markedly lower BP threshold for renal damage and
      the steeper slope of relationship between BP and renal damage in such states
      necessitates that BP be lowered into the normotensive range to prevent
      progressive renal damage. When BP is accurately measured using radiotelemetry in
      animal models, the renal protection provided by renin-angiotensin system (RAS)
      blockade is proportional to the BP reduction with little evidence of BP
      independent protection. A critical evaluation of the clinical data also suggests
      that the BP-independent renoprotection by RAS blockade has been overemphasized
      and that achieving lower BP targets is more important than the selection of
      antihypertensive regimens. However, achievement of such BP goals is difficult in
      CKD patients without aggressive diuresis, because of their proclivity for salt
      retention. The effectiveness of RAS blockers in lowering BP in patients who have
      been adequately treated with diuretics, along with their potassium-sparing and
      magnesium-sparing effects, provides a more compelling rationale for the use of
      RAS blockade in the treatment of CKD patients than any putative BP-independent
      renoprotective superiority.

PMID- 15452025
TI  - Fluvastatin enhances the inhibitory effects of a selective AT1 receptor blocker,
      valsartan, on atherosclerosis.
AB  - We investigated the effects of a 3-hydroxy-3-methylglutaryl-coenzyme A reductase
      inhibitor (statin) on the inhibitory effects of an angiotensin II type-1 receptor
      (AT1) blocker on atherosclerosis and explored cellular mechanisms. We gave
      apolipoprotein E null mice a high-cholesterol diet for 10 weeks and measured
      atherosclerotic plaque area and lipid deposition. Neither 1 mg/kg per day of
      valsartan nor 3 mg/kg per day of fluvastatin had any effect on blood pressure or
      cholesterol concentration; however, both drugs decreased plaque area and lipid
      deposition after 10 weeks. We then reduced the doses of both drugs to 0.1 mg/kg
      per day and 1 mg/kg per day, respectively. At these doses, neither drug had an
      effect on atherosclerotic lesions. When both drugs were combined at these doses,
      a significant reduction in atherosclerotic lesions was observed. Similar
      inhibitory effects of valsartan or fluvastatin on the expressions of nicotinamide
      adenine dinucleotide/nicotinamide-adenine dinucleotide phosphate oxidase subunits
      p22phox and p47phox, production of superoxide anion, the expression of monocyte
      chemoattractant protein-1, and intercellular adhesion molecule-1 expression were
      observed. These results suggest that concomitant AT1 receptor and cholesterol
      biosynthesis blockade, particularly when given concomitantly, blunts oxidative
      stress and inflammation independent of blood pressure or cholesterol-related
      effects.

PMID- 15452026
TI  - Comparison of four blood pressure indexes for the prediction of 10-year stroke
      risk in middle-aged and older Asians.
AB  - Information has been sparse on the comparison of 4 blood pressure (BP) indexes
      (systolic BP [SBP], diastolic BP [DBP], pulse pressure [PP], and mean BP [MBP])
      in relation to long-term stroke incidence, especially in middle-aged and older
      Asian people. A prospective cohort study was performed in 4989 Japanese (1523 men
      and 3466 women) aged 35 to 79 at baseline with 10 years of follow-up. End points
      included stroke incidence (total, ischemic, and hemorrhagic). Multivariate
      adjusted hazard ratios with a 1-SD higher value for each BP index were determined
      by Cox proportional hazard analyses; Wald chi2 tests were used to compare the
      strength of relationships. Analyses were also done for each of 4 age-gender
      groups consisting of men and women aged 35 to 64 and 65 to 79 years. During
      follow-up, 132 participants developed stroke. Adjusted hazard ratios for all
      strokes were 1.68 for SBP, 1.72 for DBP, and 1.80 for MBP, which were higher than
      that for PP (1.34). SBP and DBP were related positively to stroke risk after
      adjustment of each other. PP was not the strongest predictor in any age-gender
      groups among 4 BP indexes. In men aged 65 to 79 years, SBP showed the strongest
      relationship to all stoke risk (hazard ratio 1.62) among 4 BP indexes. In women
      aged 65 to 79 years, hazard ratios for all strokes were 2.48 for MBP, 2.46 for
      DBP, 2.25 for SBP, and 1.57 for PP. The long-term incident stroke risk of high BP
      in Asians should be assessed by SBP and DBP together, or by MBP, not by PP.

PMID- 15452027
TI  - Atrial natriuretic peptide dose-dependently inhibits pressure overload-induced
      cardiac remodeling.
AB  - We hypothesized that a single copy of the proatrial natriuretic peptide gene
      (Nppa+/-) would not be adequate to protect heterozygous mice against exaggerated
      cardiac hypertrophy and remodeling after pressure-overload stress. Nppa+/+,
      Nppa+/-, and Nppa-/- mice were subjected to sham surgery or transverse aortic
      constriction and fed a basal salt diet. Heart weight varied inversely with Nppa
      gene load by 1 week after either surgery. Fractional shortening did not differ
      among genotypes at baseline and fell in Nppa-/- mice only after transverse aortic
      constriction. There was a graded response in collagen deposition related to
      atrial natriuretic peptide (ANP) expression after either surgery. A robust
      interstitial and perivascular fibrosis was noted in Nppa-/- and Nppa+/- but not
      in Nppa+/+ mice after transverse aortic constriction. Our findings are consistent
      with a growing body of evidence that ANP is an important modulator of cardiac
      hypertrophy and remodeling in response to hemodynamic stress. The observation
      that partial ANP deficiency results in exaggerated hypertrophy and remodeling
      after pressure overload suggests that genetic or environmental variation in ANP
      levels may play a role in the development of cardiac hypertrophy, remodeling, and
      failure in humans.

PMID- 15452028
TI  - Hypoxia modulates adenosine receptors in human endothelial and smooth muscle
      cells toward an A2B angiogenic phenotype.
AB  - We previously reported that adenosine A2B receptor activation stimulates
      angiogenesis. Because hypoxia is a potent stimulus for the release of both
      adenosine and angiogenic factors, we tested the hypothesis that hypoxia alters
      the expression of adenosine receptors toward an "angiogenic" phenotype. We used
      human umbilical vein endothelial cells (HUVECs) and bronchial smooth muscle cells
      (BSMCs) because, under normoxic conditions, adenosine does not release vascular
      endothelial growth factor (VEGF). HUVECs expressed a characteristic A2A phenotype
      (the selective A2A agonist CGS21680 was as potent as the nonselective agonist 5'
      N-ethylcarboxamidoadenosine [NECA] in generating cAMP). Hypoxia (4.6% O2, 3
      hours) decreased A2A mRNA from 1.56+/-0.3% to 0.16+/-0.01% of beta-actin
      expression but increased A2B mRNA from 0.08+/-0.01% to 0.27+/-0.05%. Consistent
      with changes in receptor expression, CGS21680 failed to increase cAMP in hypoxic
      HUVECs, whereas NECA remained active (A2B phenotype), and NECA increased VEGF
      release from 9.5+/-1.0 to 14.2+/-1.2 pg/mL (P<0.05), indicating that increased
      A2B receptors were functionally coupled to upregulation of VEGF. Hypoxia had
      similar effects on BSMCs, increasing A2B mRNA by 2.4+/-0.3-fold, from 0.42+/
      0.04% to 1.00+/-0.13% of beta-actin. Whereas NECA had no effect on VEGF release
      in normoxic BSMCs, it increased VEGF release in hypoxic BSMCs, from 74.6+/-9.6 to
      188.3+/-16.7 pg/mL (P<0.01), and a selective A2B antagonist, CVT-6694, inhibited
      this increase. A2B receptors activated a VEGF reporter made unresponsive to
      hypoxia by mutating its hypoxia-inducible factor-1 (HIF-1) binding element,
      indicating a mechanism independent of HIF-1. In conclusion, hypoxia modulates the
      expression of adenosine receptors in human endothelial and smooth muscle cells
      toward an A2B"angiogenic" phenotype.

PMID- 15452029
TI  - Association between factor VII polymorphisms and blood pressure: the Stanislas
      Cohort.
AB  - The purpose this study was to determine whether Arg353Gln and -323Del/Ins
      polymorphisms of factor VII (FVII) are related to blood pressure levels and
      hypertension. Subjects were drawn from the Stanislas Cohort, a longitudinal,
      familial French cohort examined twice since 1994. The "blood pressure study"
      included 1342 subjects free of medication use that could affect blood pressure.
      The "hypertension study" included 645 normotensive and 77 hypertensive adult
      subjects. Association with hypertension was also studied in 547 hypertensives
      enrolled in a clinical trial and in 624 normotensives drawn from the Stanislas
      Cohort. In the "blood pressure study," parents with the 353Gln or -323Ins allele
      had lower blood pressures than did noncarriers at each examination, independent
      of covariates (0.01< or =P< or =0.05, except for diastolic blood pressure [DBP]
      at baseline, where P=0.103). Similarly significant relations were observed in
      their offspring (P< or =0.05, except for systolic blood pressure [SBP] at 5
      years, where P=0.186). In a representative subgroup of 267 individuals, the 
      323Del/Ins polymorphism was significantly associated with plasma FVII levels in
      both parents and offspring (P<0.001). FVII levels in plasma were significantly
      correlated with SBP and DBP in parents but not in offspring. After inclusion of
      both FVII levels and the -223Del/Ins in the same model in parents, only FVII
      levels remained significantly associated with SBP and DBP. The "hypertension
      study" revealed that the 353Gln and -323Ins alleles were related to decreased
      risk (odds ratio [OR]=0.554, 95% confidence interval [CI], 0.362 to 0.848, and
      OR=0.475, 95% CI, 0.299 to 0.755, respectively). These results suggest that the
      FVII gene may be a susceptibility locus for hypertension.

PMID- 15452030
TI  - Mapping the genetic determinants of hypertension, metabolic diseases, and related
      phenotypes in the lyon hypertensive rat.
AB  - The complex nature of hypertension makes identifying the pathophysiology and its
      genetic contributions a challenging task. One powerful approach for the genetic
      dissection of blood pressure regulation is studying inbred rat models of
      hypertension, as they provide natural allele variants but reduced heterogeneity
      (both genetic and etiologic). Furthermore, the detailed physiologic studies to
      which the rat is amenable allow for the determination of intermediate phenotypes.
      We have performed a total genome scan in offspring of an F2 intercross between
      the Lyon hypertensive (LH) and Lyon normotensive rat strains to identify linkage
      of anthropometric, blood pressure, renal, metabolic, and endocrine phenotypes.
      Quantitative trait locus (QTL) regions involved in blood pressure regulation, end
      stage organ damage, body and organ weight, and lipid metabolism in the LH rat
      were identified on chromosomes 1, 2, 3, 5, 7, 10, 13, and 17, with 2 phenotypes
      associated with the metabolic syndrome identified on chromosomes 1 and 17.
      Regions on chromosomes 2, 13, and 17 were revealed to be important for blood
      pressure regulation. Regions on chromosome 17 were found to significantly
      contribute to both metabolic homeostasis and blood pressure regulation; 2
      aggregates of a total of 23 QTLs were identified, including several "intermediate
      phenotypes." These intermediate phenotypes may be used as closer surrogates to
      the mechanisms leading to hypertension and metabolic dysfunction in the LH rat.

PMID- 15452031
TI  - Primed polymorphonuclear leukocytes, oxidative stress, and inflammation antecede
      hypertension in the Sabra rat.
AB  - Hypertension is accompanied by systemic oxidative stress, inflammation, and
      priming of peripheral polymorphonuclear leukocytes (PMNLs), yet the involvement
      of these factors in the pathophysiology of hypertension is incompletely
      understood. We investigated the relationship between oxidative stress, primed
      PMNLs, and inflammation and the development of hypertension in the Sabra rat
      model of salt-sensitive hypertension. Sabra hypertension-resistant rats (SBN/y)
      (salt-resistant) and Sabra hypertension-prone rats (SBH/y) (salt-sensitive) were
      studied under normal conditions or during salt loading. Systolic blood pressure
      (BP) was measured by the tail-cuff method. The extent of oxidative stress was
      evaluated by the rate of superoxide release from PMNLs, plasma-reduced
      glutathione (GSH) levels, malondialdehyde (MDA) levels (estimated by
      thiobarbituric acid-reacting substances), and plasma-carbonylated fibrinogen
      (Western blotting). Plasma fibrinogen levels and the peripheral PMNL count served
      as indices of inflammation. In SBH/y and SBN/y provided regular chow without salt
      loading, BP did not rise above baseline values, yet superoxide release, plasma
      MDA, carbonylated fibrinogen, and PMNL count were higher in SBH/y than in SBN/y,
      whereas GSH levels were lower in SBH/y. Four weeks of salt loading resulted in a
      gradual increase in systolic BP in SBH/y to 205+/-3 mm Hg, whereas BP remained in
      SBN/y at baseline normotensive levels. All the parameters reflecting oxidative
      stress and inflammation were further aggravated with the development of
      hypertension in salt-loaded SBH/y. We conclude that primed PMNLs, oxidative
      stress, and inflammation antecede the development of hypertension in this
      experimental model of hypertension.

PMID- 15452032
TI  - Fueling the hypertrophied heart.

PMID- 15452033
TI  - Interaction between an 11betaHSD1 gene variant and birth era modifies the risk of
      hypertension in Pima Indians.
AB  - 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) is a candidate gene for
      hypertension, diabetes, and obesity through altered glucocorticoid production.
      This study explored the association of 11betaHSD1 gene variants with diabetes,
      hypertension, and obesity in a longitudinal population study of American Indians
      (N=918; exams=5508). In multivariate mixed models assuming an additive effect of
      genotype, a 5' upstream variant (rs846910) was associated with blood pressure
      (diastolic blood pressure beta=1.58 mm Hg per copy of the A allele, P=0.0008;
      systolic blood pressure beta=2.28 mm Hg per copy of the A allele, P=0.004; mean
      arterial blood pressure beta=1.83 mm Hg per copy of the A allele, P=0.0006) and
      hypertension (odds ratio=1.27 per copy of the A allele, P=0.02). However, birth
      date modified these associations (test for interaction: diastolic blood pressure
      P=0.16; systolic blood pressure P=0.007; mean arterial blood pressure P=0.01),
      such that the magnitude and direction of association between genotype and blood
      pressure changed with time. Finally, in models controlling for potential
      confounding by population stratification, we observed evidence of within-family
      effects for blood pressure (diastolic blood pressure beta=1.77 mm Hg per copy of
      the A allele, P=0.004; systolic blood pressure beta=2.04 mm Hg per copy of the A
      allele, P=0.07; mean arterial blood pressure beta=1.85 mm Hg per copy of the A
      allele, P=0.01) and for hypertension (odds ratio=1.26 per copy of the A allele;
      P=0.08). No association was observed for obesity. Associations with diabetes were
      similar in magnitude as reported previously but were not statistically
      significant. These data demonstrate association between genetic variability at
      11betaHSD1 with hypertension, but these effects are modified by environmental
      factors.

PMID- 15452034
TI  - Cardiorespiratory fitness, physical activity, and arterial stiffness: the
      Northern Ireland Young Hearts Project.
AB  - Poor cardiorespiratory fitness and low physical activity have been identified as
      determinants of greater arterial stiffness, a mechanism that can partially
      explain the association of both variables with increased cardiovascular disease.
      However, the nature of these associations are not clear because cardiorespiratory
      fitness and physical activity can both mediate and confound the associations of
      one another with arterial stiffness. This issue was therefore examined in a
      population-based cohort of young adults. Subjects included 405 young men and
      women participating in an ongoing longitudinal study, the Northern Ireland Young
      Hearts Project. Pulse wave velocity was used to determine arterial stiffness in 2
      arterial segments (aortoiliac and aortodorsalis pedis) using a noninvasive
      optical method. Cardiovascular fitness was estimated with a submaximal cycle test
      of physical work capacity and physical activity was estimated using a modified
      Baecke questionnaire. Associations were investigated with the use of multiple
      linear regression models with adjustment for potential confounders and/or
      intermediate variables. Cardiorespiratory fitness and sports-related physical
      activity (but not leisure- and work-related physical activity) were inversely
      associated with arterial stiffness in young adults. The associations between
      sports-related physical activity and arterial stiffness were strongly mediated by
      cardiorespiratory fitness, whereas physical activity levels did not disturb the
      associations between cardiopulmonary fitness and arterial stiffness. These
      findings suggest that arterial stiffness-related benefits of exercise are most
      likely to accrue if exercise prescription in young adults targets improvements in
      cardiorespiratory fitness.

PMID- 15452035
TI  - Arterial pressure response to the antioxidant tempol and ETB receptor blockade in
      rats on a high-salt diet.
AB  - We hypothesized that increased superoxide contributes to mean arterial pressure
      (MAP) regulation in male Sprague-Dawley rats fed a high-salt diet and/or during
      endothelin (ET(B)) receptor blockade. Four groups on either a normal- or a high
      salt diet were studied for 1 week: (1) control; (2) tempol, a superoxide
      dismutase mimetic, in their drinking water (1 mmol/L); (3) A-192621, an ET(B)
      antagonist, in their food (10 mg/kg daily); or (4) both tempol and A-192621.
      Without ET(B) blockade, tempol had no effect on MAP (telemetry) in rats on the
      normal-salt diet but significantly reduced MAP in rats on the high-salt diet
      (100+/-3 vs 112+/-2 mm Hg, P<0.05). On the normal-salt diet, A-192621 increased
      MAP with or without tempol. Under high-salt conditions, tempol attenuated the
      increase in MAP produced by A-192621, but only during the initial days of
      treatment. Plasma 8-isoprostanes were increased in all rats on the high-salt diet
      and were further increased after 3 days of A-192621 but not after 7 days; tempol
      inhibited the increase produced by A-192621 but had no influence on the increase
      produced by high salt. H2O2 excretion was significantly higher in rats on a high
      salt diet for the 7-day drug treatment compared with those on a normal-salt diet.
      Tempol further increased H2O2 excretion in rats on a high-salt diet, an effect
      accelerated in A-192621-treated rats. These data suggest that blood pressure
      lowering by tempol in rats on a high-salt diet may be unrelated to reductions in
      superoxide and that renal H2O2 may account for the limited ability of tempol to
      attenuate hypertension produced by ET(B) receptor blockade.

PMID- 15452036
TI  - Short- and long-term changes in plasma inflammatory markers associated with
      preeclampsia.
AB  - Preeclampsia is characterized by hypertension, dyslipidemia, and increased
      systemic inflammatory response and has been associated with an increased maternal
      risk of cardiovascular disease later in life. Low-grade chronic inflammation is a
      risk factor for cardiovascular disease. This study examined changes in
      inflammatory markers prospectively during pregnancy, the current inflammatory
      status of women who had a pregnancy complicated by preeclampsia 20 years
      previously against matched controls, and the association between inflammatory
      genes and risk of preeclampsia in a case (n=106) control (n=212) study. In
      control pregnancies (n=34), mean interleukin-10 (IL-10) levels increased 38%
      (P=0.012) and tumor necrosis factor-alpha (TNF-alpha) by 33% (P=0.024) between
      the first and third trimesters. The mean preeclampsia group IL-10 and TNF-alpha
      rose by 43% (P=0.013 and P=0.0065, respectively) from the first to the third
      trimester. In women with preeclampsia only, plasma IL-6 increased from the first
      to the third trimester (1.66 [2.04] to 2.94 [2.47] pg/mL; P=0.0004). Twenty years
      after the index pregnancy, women who had had preeclampsia demonstrated
      significantly higher IL-6 to IL-10 ratio (3.96 [6.07] versus 2.12 [1.89];
      P=0.034) compared with a healthy index pregnancy 20 years previously, that
      persisted after adjustment for smoking and current body mass index. The IL-1beta
      (C-511T), IL-6 (G-174C), TNF-alpha (G-308A), E-selectin (S128R), intercellular
      adhesion molecule-1 (K469E), and C-reactive protein (C1059G) polymorphisms were
      not associated with risk of developing preeclampsia. In conclusion, preeclampsia
      is associated with short- and long-term changes in inflammatory status.

PMID- 15452037
TI  - Recovery from form-deprivation myopia in rhesus monkeys.
AB  - PURPOSE: Although many aspects of vision-dependent eye growth are qualitatively
      similar in many species, the failure to observe recovery from form-deprivation
      myopia (FDM) in higher primates represents a significant potential departure. The
      purpose of this investigation was to re-examine the ability of rhesus monkeys
      (Macaca mulatta) to recover from FDM. METHODS: Monocular form deprivation was
      produced either with diffuser spectacle lenses (n = 30) or by surgical eyelid
      closure (n = 14). The diffuser-rearing strategies were initiated at 24 +/- 3 days
      of age and continued for an average of 115 +/- 20 days. Surgical eyelid closure
      was initiated between 33 and 761 days of age and maintained for14 to 689 days.
      After the period of form deprivation, the animals were allowed unrestricted
      vision. The ability of the animals to recover from treatment-induced refractive
      errors was assessed periodically by retinoscopy, keratometry, and A-scan
      ultrasonography. Control data were obtained from 35 normal monkeys. RESULTS: At
      the onset of unrestricted vision, the deprived eyes of 18 of the diffuser-reared
      monkeys and 12 of the lid-sutured monkeys were at least 1.0 D less hyperopic or
      more myopic than their fellow eyes. The mean (diffuser = -4.06 D, lid-suture = 
      4.50 D) and range (diffuser = -1.0 to -10.19 D, lid-suture = -1.0 to -10.25 D) of
      myopic anisometropia were comparable in both treatment groups. All 18 of these
      diffuser-reared monkeys demonstrated recovery, with 12 animals exhibiting
      complete recovery. The rate of recovery, which was mediated primarily by
      alterations in vitreous chamber growth rate, declined with age. None of the lid
      sutured monkeys exhibited clear evidence of recovery. Instead, 8 of the 12 lid
      sutured monkeys exhibited progression of myopia. CONCLUSIONS: Like many other
      species, young monkeys are capable of recovering from FDM. However, the potential
      for recovery appears to depend on when unrestricted vision is restored, the
      severity of the deprivation-induced axial elongation, and possibly the method
      used to produce FDM.

PMID- 15452038
TI  - Compensation for experimentally induced hyperopic anisometropia in adolescent
      monkeys.
AB  - PURPOSE: Early in life, the optical demand associated with the eye's effective
      refractive state regulates emmetropization in many species, including primates.
      However, the potential role of optical demand and/or defocus in the genesis of
      common refractive errors, like myopia, that normally develop much later in life
      is not known. The purpose of this study was to determine whether chronic optical
      defocus alters refractive development in monkeys at ages corresponding to when
      myopia typically develops in children. METHODS: A hyperopic anisometropia was
      produced in seven adolescent rhesus monkeys by photorefractive keratectomy (PRK)
      with an excimer laser. Standard treatment algorithms for correcting myopia in
      humans were used to selectively flatten the central cornea of one eye thereby
      producing relative hyperopic refractive errors in the treated eyes. The laser
      ablation zones were 5.0 mm in diameter and centered on the monkeys' pupils. The
      laser procedures were performed when the monkeys were 2 to 2.5 years old, which
      corresponded to onset ages between approximately 8 and 10 human years. The ocular
      effects of the induced anisometropia were assessed by corneal topography,
      retinoscopy, and A-scan ultrasonography. RESULTS: By approximately 30 days after
      PRK, the experimentally induced refractive errors had stabilized and the treated
      eyes were between +0.75 and +2.25 D more hyperopic than their fellow eyes.
      Subsequently, over the next 300 to 400 days, six of the seven monkeys showed
      systematic reductions in the degree of anisometropia. Although some regression in
      corneal power occurred, the compensating refractive changes were primarily due to
      relative interocular differences in vitreous chamber growth. CONCLUSIONS: Vision
      dependent mechanisms that are sensitive to refractive error are still active in
      adolescent primates and probably play a role in maintaining stable refractive
      errors in the two eyes. Consequently, conditions that result in consistent
      hyperopic defocus could potentially contribute to the development of juvenile
      onset myopia in children.

PMID- 15452039
TI  - Eye shape in emmetropia and myopia.
AB  - PURPOSES: To determine axial, vertical, and horizontal eye dimensions in myopic
      and emmetropic eyes by using magnetic resonance imaging (MRI) and to relate these
      to different ocular expansion models of myopia development. METHODS: The internal
      length (cornea to retina), height and width (both retina to retina) were measured
      in emmetropic and myopic eyes (up to -12 D) of 88 participants aged 18 to 36
      years. Participants were positioned supine in a clinical MRI scanner. The
      fixation target was imaged straight ahead of the subject by an overhead 45
      degrees inclined mirror. Eye images were acquired with a 7.5-cm receive-only
      radio frequency surface coil. Axial (horizontal through middle of eye) and
      sagittal (vertical through visual axis) sections were taken with a T(1)-weighted
      fast spin-echo sequence. RESULTS: With an increase in myopic refractive
      correction, myopic eyes became much larger in all three dimensions, but more so
      in length (0.35 mm/D, 95% confidence interval [CI] 0.28-0.40) than in height
      (0.19 mm/D, 95% CI 0.09-0.29) and more so in height than in width (0.10 mm/D, 95%
      CI 0.01-0.20). Based on height and length dimensions, 25% and 29% of myopic eyes
      exclusively fitted global expansion and axial elongation models, respectively.
      Based on width and length dimensions, 17% and 39% of myopic eyes exclusively
      fitted the global expansion and axial elongation models, respectively.
      CONCLUSIONS: Although there are considerable individual variations, in general
      myopic eyes are elongated relative to emmetropic eyes, more in length than in
      height and even less in width. Approximately a quarter of the myopic participants
      fitted each of the global expansion or axial elongation model exclusively. The
      small proportions are due primarily to the large variability in the dimensions of
      emmetropic eyes.

PMID- 15452040
TI  - Pathogenesis of persistent hyperplastic primary vitreous in mice lacking the arf
      tumor suppressor gene.
AB  - PURPOSE: Persistent hyperplastic primary vitreous (PHPV) is an idiopathic
      developmental eye disease associated with failed involution of the hyaloid
      vasculature. The present work addressed the pathogenesis of PHPV in a mouse model
      that replicates many aspects of the human disease. METHODS: Ophthalmoscopic and
      histologic analyses documented pathologic processes in eyes of mice lacking the
      Arf gene compared with Ink4a-deficient and wild-type control animals.
      Immunohistochemical staining, in situ hybridization, and RT-PCR demonstrated the
      expression of relevant gene products. Arf gene expression was determined by in
      situ hybridization using wholemounts of wild-type mouse eyes and by
      immunofluorescence staining for green fluorescent protein (GFP) in Arf(+/GFP)
      heterozygous knock-in mouse eyes. RESULTS: Abnormalities in Arf(-/-) mice
      mimicked those found in patients with severe PHPV. The mice had microphthalmia;
      fibrovascular, retrolental tissue containing retinal pigment epithelial cells and
      remnants of the hyaloid vascular system; posterior lens capsule destruction with
      lens degeneration and opacity; and severe retinal dysplasia and detachment. Eyes
      of mice lacking the overlapping Ink4a gene were normal. Arf was selectively
      expressed in perivascular cells within the vitreous of the postnatal eye. Cells
      composing the retrolental mass in Arf(-/-) mice expressed the Arf promoter. The
      remnant hyaloid vessels expressed Flk-1. Its ligand, vascular endothelial growth
      factor (Vegf), was expressed in the retrolental tissue and the adjacent
      dysplastic neuroretina. CONCLUSIONS: Arf(-/-) mice have features that accurately
      mimic severe PHPV. In the HVS, Arf expression in perivascular cells may block
      their accumulation or repress Vegf expression to promote HVS involution and
      prevent PHPV.

PMID- 15452041
TI  - Cone cell survival and downregulation of GCAP1 protein in the retinas of GC1
      knockout mice.
AB  - PURPOSE: To examine the spatial and temporal characteristics of cone cell
      survival and the expression of guanylate cyclase-activating proteins (GCAPs) in
      the guanylate cyclase (GC)-1 knockout (KO) mouse retina. METHODS:
      Immunohistochemical analyses with peanut agglutinin and an antibody specific for
      cone transducin were used to examine cone cell survival in the GC1 KO retina at
      4, 5, 9, 16, and 24 weeks of age. Immunohistochemical and Northern and Western
      blot analyses were used to examine the expression of GCAP1 and GCAP2 in 4- to 5
      week-old mice. RESULTS: The number of cone cells appeared normal throughout the
      superior and inferior retinal regions in 4- and 5-week-old GC1 KO mice but
      gradually decreased by 6 months. Cone cell loss was exacerbated in the inferior
      retinal region, with only 2% to 8% remaining by 6 months of age; however, 40% to
      70% of the cone cells survived in the superior region at this age. GCAP1 and
      GCAP2 protein levels were downregulated in GC1 KO retinas at 4 weeks of age and
      GCAP1 immunostaining was absent from the photoreceptor outer segments.
      CONCLUSIONS: The results of this study show that the rate of cone cell loss in
      the GC1 KO mouse is comparable to that previously described in the GUCY1*B
      chicken and in humans with Leber congenital amaurosis (LCA)-1. The GCAP
      expression data, when combined with those of previous electrophysiological
      studies of the GC1 KO mouse retina, provide evidence that GC1-GCAP1 interactions
      are essential for cone cell function in mice and that GC2 and GCAP2 activities
      contribute to the rod cell response in the absence of GC1.

PMID- 15452042
TI  - Microsatellite instability and MLH1 promoter methylation in human retinoblastoma.
AB  - PURPOSE: To investigate the link between microsatellite instability and
      epigenetic silencing of the MLH1 gene in the human retinoblastoma genome.
      METHODS: Methylation at the 5' region of MLH1 was studied, along with its protein
      expression level by using immunohistochemical staining in 51 retinoblastoma
      tumors and 2 retinoblastoma cell lines. Also assessed was the genomic stability
      of 26 retinoblastoma DNAs from microdissected tumor tissue and matched normal
      retina tissue obtained from the same patient by microsatellite instability (MSI)
      analysis. The National Cancer Institute-designed reference panel, and 85 markers
      on chromosomes 1, 6, 9, and 13 were used. RESULTS: Hypermethylation of the MLH1
      promoter was detected in the WERI-Rb1 cell line and in 34 (67%) of the 51 tumors,
      but not in cell line Y79 and the other 17 tumors. MLH1 hypermethylation was
      associated with null MLH1 protein expression (P < 0.0005) and with well
      differentiated histology (P < 0.05). MSI at three markers (D2S123, D6S470, and
      D13S265) was frequently identified among 26 retinoblastoma specimens with matched
      normal DNA. Among these 26 retinoblastomas, high-frequency MSI (MSI-H) tumors
      were detected in 19% (5/26) and low-frequency MSI (MSI-L) in another 19% (5/26).
      The remaining 62% (15/26) were genetically stable (MSS). MSI status (MSS, MSI-L,
      and MSI-H) was not associated with MLH1 promoter hypermethylation (P = 0.088;
      Kruskal-Wallis test). CONCLUSIONS: Epigenetic silencing of the DNA repair gene
      MLH1 by promoter hypermethylation is a frequent event in retinoblastoma. The
      results showed that somatic genetic changes involving MSI occur in a subset of
      retinoblastoma and implicated the presence of a defective DNA mismatch repair
      pathway resulting in MSI in retinoblastoma.

PMID- 15452043
TI  - Expression of P2Y1, P2Y2, P2Y4, and P2Y6 receptor subtypes in the rat retina.
AB  - PURPOSE: To elucidate the expression pattern of different types of metabotropic
      P2Y receptors in the adult rat retina. METHODS: Qualitative RT-PCR was used to
      investigate the expression profile of different P2Y receptor subtypes (P2Y1,
      P2Y2, P2Y4, and P2Y6), and in situ hybridization studies were performed to show
      their cellular localization within the retina. Immunohistochemical staining was
      used to detect the corresponding P2Y proteins (P2Y1, P2Y2, and P2Y4) and their
      cellular localization. Southern blot analysis and sequencing verified the
      identity of the P2Y PCR products. RESULTS: RT-PCR revealed the presence of P2Y1, 
      2, -4, and -6 mRNA in the neural retina and the retinal pigment epithelium (RPE)
      and choroid. In situ hybridization showed labeling in the retinal ganglion cell
      layer for all four P2Y receptor subtypes, although the intensity varied. In
      addition, staining for P2Y1, -4, and -6 mRNA was shown in the inner nuclear
      layer, but was absent for the P2Y2 receptor subtype. Immunohistochemistry showed
      intense staining for P2Y1, -2, and -4 in the ganglion cell layer and the outer
      plexiform layer. There was also a specific subtype staining in the inner
      plexiform layer (P2Y2, -4), the inner (P2Y1, -4) and outer (P2Y1) nuclear layers
      and the inner segments of the photoreceptors (P2Y1, -2). discussion. The data
      suggest that extracellular nucleotides may play complex roles as autocrine
      paracrine mediators and may have neuromodulatory effects in the retina through
      metabotropic P2Y receptors.

PMID- 15452044
TI  - Reading performance in patients with retinitis pigmentosa: a study using the
      MNREAD charts.
AB  - PURPOSE: To evaluate the relationship between reading performance and severity of
      disease in patients with retinitis pigmentosa (RP), assessed with routine
      clinical psychophysical visual tests. METHODS: Seventy-six consecutive patients
      with RP (145 eyes), with reading acuity of at least 1.6 logMAR (logarithm of the
      minimum angle of resolution) in at least one eye, were examined. Each patient
      underwent a complete ophthalmic evaluation, including visual acuity (Early
      Treatment Diabetic Retinopathy Study [ETDRS] charts), contrast sensitivity (Pelli
      Robson charts), visual field perimetry (Humphrey central 30-2 full-threshold
      program; Carl Zeiss Meditec, Dublin, CA), and a test of reading acuity, critical
      print size, and maximum reading speed (Minnesota Reading charts [MNREAD]).
      RESULTS: Reading acuity was 1.0 logMAR or more in the better eye of all but six
      (92%) patients. Maximum reading speed was better than 100 words per minute in the
      better eye of 59 (78%) subjects. Moderate to severe reading impairment, defined
      as reading acuity of 0.4 logMAR or worse, was observed in the better eye of 47
      (62%) patients. EDTRS visual acuity of 0.3 logMAR (20/40) or worse was 89%
      sensitive and 66% specific when used as a criterion to define reading impairment.
      Contrast sensitivity and visual acuity correlated significantly with all three
      reading components, whereas mean light sensitivity in the central visual field (6
      degrees ) demonstrated a higher correlation with maximum reading speed. The
      number of years elapsed since the diagnosis of RP was a strong negative predictor
      of reading performance when clinical visual tests were taken into account,
      whereas a better reading ability characterized the patients with RP who had a
      higher level of education. A reduced reading speed with larger print size was
      found in 30 eyes (21%). This correlated with central light sensitivity, as it was
      more common among eyes with a mean sensitivity of <10 dB. CONCLUSIONS: The
      reading performance of most patients with RP is only moderately impaired. It
      correlates with contrast sensitivity, visual acuity, and visual field. It should
      be assessed in all cases, as disability can ensue, even when visual acuity is
      preserved. In patients with RP with poor reading performance, there is little
      potential for high-magnification devices because visual field constriction
      affects the reading rate.

PMID- 15452045
TI  - Effect of radiation dose on ocular complications after iodine brachytherapy for
      large uveal melanoma: empirical data and simulation of collimating plaques.
AB  - PURPOSE: To calculate radiation doses to intraocular tissues in iodine
      brachytherapy (IBT) for large uveal melanoma, to study their relationship to
      ocular complications, and to assess a modified plaque design to reduce doses to
      the macula and optic nerve. METHODS: Ninety-six patients with a uveal melanoma,
      classified as large according to the Collaborative Ocular Melanoma Study
      criteria, underwent primary IBT. Median tumor height and diameter were 10.7
      (range, 4.5-16.8) and 16.5 (range, 7.3-25.0) mm, respectively, and median follow
      up was 3.5 years (range, 0.3-10.4). Each IBT was retrospectively modeled with a
      plaque simulator to calculate doses and dose rates to ocular tissues. Cox
      proportional hazards regression was used to assess their association with time to
      ocular complications, low vision, and blindness (20/70 or worse and loss of
      20/400, respectively). A collimating plaque design was assessed by replacing the
      actual plaque with the modified one in each model. RESULTS: Median doses to tumor
      apex and base were 81 (range, 40-158 Gy) and 384 (range, 188-1143) Gy,
      respectively, and the median dose rates at these points were 53 (range, 11-204)
      and 289 (range, 84-1213) cGy/h, respectively. Median doses to the lens, macula,
      and optic disc were 69 (range, 20-141), 79 (range, 12-632), and 83 (range, 10
      377) Gy, respectively. Dose to the lens was associated with cataract (hazard
      ratio [HR] 1.15 for each 10-Gy increase, P = 0.002), and dose to the optic disc
      with optic neuropathy (HR 1.08, P = 0.001). Dose to the macula predicted low
      vision (HR 1.06, P = 0.025) and blindness (HR 1.10, P < 0.001). A collimating
      design provided a median reduction of 36 (range, +19 to -198) and 30 (range, +9
      to -160) Gy in modeled doses to the macula and optic disc, respectively.
      CONCLUSIONS: Simulated dose distribution together with tumor height predicts
      major complications and vision loss after IBT. Simulation suggests that
      clinically meaningful dose reduction to normal tissues is feasible with a
      redesigned brachytherapy protocol, which may help to reduce complications and
      vision loss after IBT of large uveal melanoma.

PMID- 15452046
TI  - Pharmacokinetic-pharmacodynamic modeling of the effect of triamcinolone acetonide
      on central macular thickness in patients with diabetic macular edema.
AB  - PURPOSE: To develop a population model capable of describing the profile of the
      effect of intravitreal triamcinolone acetonide in the treatment of diabetic
      diffuse macular edema. METHODS: The results of 51 injections in 37 eyes (33
      patients) with diffuse diabetic macular edema were studied, by using population
      pharmacokinetic-pharmacodynamic modeling, without triamcinolone concentration
      measurements. This approach was supported by the pharmacokinetic hypothesis that
      the intravitreal triamcinolone concentration decreases in accordance with an
      exponential biphasic equation. Central macular thickness (CMT), measured by
      optical coherence tomography was chosen as the pharmacodynamic parameter.
      RESULTS: The pharmacodynamic profile of the effect of triamcinolone on CMT was
      characterized by a curve in three phases: a fast decrease, a steady state, and a
      relapse. The confidence interval of most of the estimated parameters of the model
      was narrow. The mean estimated half-life of triamcinolone +/- SD was 15.4 +/- 1.9
      days, and the mean maximum duration of its effect (+/-SD), 140 +/- 17 days.
      CONCLUSIONS: Pharmacokinetic-pharmacodynamic modeling using CMT constitutes a
      valid alternative to pharmacokinetic studies. This approach worked excellently in
      the present study, and the results are consistent with those published for the
      intraocular pharmacokinetics of triamcinolone acetonide in the human eye. The
      authors conclude that this type of investigation is of interest, as it avoids
      intraocular measurements as far as possible.

PMID- 15452047
TI  - The impact of visual impairment on functional vision of children in rural South
      India: the Kariapatti Pediatric Eye Evaluation Project.
AB  - PURPOSE: To determine the impact of visual impairment on functional vision of
      children in a rural population of south India. METHODS: A visual function
      questionnaire (LVP-VFQ) was administered to 1194 children aged 7 to 15 years
      identified through a systematic random sampling technique from 144 hamlets of
      Kariapatti in rural south India as part of a larger population-based project.
      Visual acuity estimations and clinical examinations for morbidity were performed
      in these 1194 children. A Rasch analysis was performed to validate the use of the
      instrument in this population. Bootstrap estimates (95% confidence intervals) of
      the regression coefficients were used to compare visual function scores between
      children with normal sight and children with uncorrected monocular and binocular
      visual impairment. RESULTS: The mean age of children was 10.3 +/- 2.1 years. The
      reliability estimates were 0.82 for person ability and 0.88 for item difficulty
      parameters, according to the Rasch analysis. A separation index of 2.15 was
      obtained for person measures and 2.74 for item measures, and the mean square
      infit and outfit statistics were 1.03 (Z(STD) 0.1) and 0.99 (Z(STD) -0.1),
      respectively. Children with monocular visual impairment (bootstrap estimate
      [95%CI] -0.05 [-0.08 to -0.01]) and binocular visual impairment (bootstrap
      estimate [95%CI] -0.09 [-0.11 to -0.07]) were more likely to have functional
      visual deficits than were normally sighted peers. CONCLUSIONS: Monocular or
      binocular visual impairment impacts on the functional vision of children in this
      rural population. Further studies are needed to determine the impact of treatment
      of visual impairment on functional vision in children of this population.

PMID- 15452048
TI  - Impact of family history of high myopia on level and onset of myopia.
AB  - PURPOSE: To investigate the impact of a positive family history of high myopia on
      the level and onset of myopia and its ocular components. METHODS: A cross
      sectional study was conducted. The participants (aged 17 to 45 years) were
      categorized into four groups: normal, mild, moderate, and high myopia. The age of
      first glasses for myopia was used as the onset of myopia. The impact of the
      family history on the level and the onset of myopia was quantified. Parental
      effect on corneal curvature (CC), anterior chamber depth (ACD), and axial length
      (AXL) was analyzed. RESULTS: The study included 185 normal subjects, 170 mild,
      140 moderate, and 392 high myopes. Family history was strongly associated with
      the probands' status (P < 6 x 10(-12)). When there was >or=1 highly myopic
      parent, the odds ratios (ORs) of developing mild or moderate myopia were between
      2.5 and 3.7 (95% CI: 1.1-6.5) and the ORs of having high myopia were > 5.5 (95%
      CI: 3.2-12.6). A strong association (P = 2 x 10(-6)) between parental myopic
      state and the AXL in the subjects was also found, but there was no statistical
      relationship for ACD or CC. There was an association between high myopia in
      parents and the onset of myopia in children. Siblings had a weaker association
      with the level of myopia and had no effect on the onset of myopia. CONCLUSIONS:
      This study found strong familial effects on the level and onset of myopia even
      after adjusting for environmental factors. The parental effect on ocular
      components in their offspring was primarily on AXL.

PMID- 15452049
TI  - An assessment of self-reported disease classification in epidemiological studies
      of dry eye.
AB  - PURPOSE: To evaluate the reliability of self-reported dry eye disease status and
      patient-related predictors of misclassification in contact lens wearers. METHODS:
      Patients completed the Contact Lens Dry Eye Questionnaire (CLDEQ) short form on
      two occasions. Test-retest reliability of the CLDEQ composite score was
      determined using the 95% limits of agreement (LoA) and an intraclass correlation
      coefficient (ICC). The kappa statistic was used to determine reliability of
      disease-classification-based CLDEQ composite score cutoff points. Predictors of
      misclassification were determined by multivariate logistic regression. RESULTS:
      The sample included 274 patients. The range of CLDEQ composite scores from both
      visits was -1.83 to 4.50 and the mean difference between administrations was 
      0.05 +/- 0.75 (P = 0.30). The 95% LoA of the CLDEQ composite score were -1.51 to
      1.42 and the ICC was 0.61 (95% confidence interval [CI]: 0.53-0.68). Calculations
      using the lower limit of the 95% CI showed that three administrations of the
      survey would be required to obtain a more desirable ICC (0.70). The kappa
      statistic for reliability of dry eye disease classification was 0.58 (95% CI:
      0.48-0.67). Logistic regression showed a significant interaction between gender
      (females) and younger age (P = 0.02) in relation to misclassification of self
      reported dry eye disease status. CONCLUSIONS: The reliability of self-reported
      dry eye disease classification in contact lens wearers is moderate. In
      epidemiologic studies of factors associated with self-reported disease status,
      investigators may be well advised to consider using multiple administers of such
      outcome instruments and controlling for sociodemographic characteristics to
      maintain internal validity.

PMID- 15452050
TI  - Perceived visual ability for functional vision performance among persons with low
      vision in the Indian state of Andhra Pradesh.
AB  - PURPOSE: To determine the distribution of perceived visual ability for functional
      vision performance among persons with low vision in the Indian state of Andhra
      Pradesh. METHODS: As part of a population-based epidemiologic study, the Andhra
      Pradesh Eye Disease Study (APEDS), a 16-item visual function questionnaire was
      designed and applied to 7363 persons older than 15 years, to record the levels of
      difficulty perceived by the subjects. Of these, 123 persons were found to have
      low vision. Rasch analysis was used to convert the ordinal difficulty ratings of
      these 123 persons into interval measures of perceived visual ability for
      functional vision. RESULTS: Content validity of the questionnaire was
      demonstrated by good separation indices (3.17 and 5.44) and high reliability
      scores (0.91 and 0.97) for person and item parameters. Construct validity was
      shown with model fit statistics. Criterion validity of the questionnaire was
      shown by good discrimination among the general vision ratings. The functional
      situation that required the least visual ability was "reaching an object farther
      or closer than you thought"; the situation requiring the most visual ability was
      "recognizing small objects." Bivariate regression analysis determined that for
      every unit of logMAR visual acuity, perceived visual ability for functional
      vision decreased by 2.9 logit, which could explain 32% of the variability in the
      person measure. CONCLUSIONS: The described assessment, across a range of visual
      problems, is a valid way to measure perceived ability for functional vision in
      persons with low vision. Perceived visual ability varies with every unit of
      logarithm of the minimum angle of resolution (logMAR) visual acuity.

PMID- 15452051
TI  - Corneal fibroblasts respond rapidly to changes in local mechanical stress.
AB  - PURPOSE: To investigate the response of corneal fibroblasts to local changes in
      extracellular matrix (ECM) tension. METHODS: Rabbit and human corneal fibroblasts
      were plated inside fibrillar collagen matrices. After 18 to 72 hours, a glass
      microneedle was inserted into the ECM and either pushed toward a cell to reduce
      local tension, or pulled away to increase tension. Time-lapse differential
      interference contrast (DIC) imaging was performed both before and after needle
      micromanipulation. ECM displacements were quantified, and strain maps were
      generated by finite element modeling. In some experiments, cells were treated
      with the Rho-kinase inhibitor Y-27632 either 30 minutes before, or 1 hour after
      they were pushed with the microneedle. Changes in focal adhesion organization
      were also evaluated in a subset of cells expressing green fluorescent protein
      (GFP)-zyxin, by simultaneous fluorescent and DIC imaging. RESULTS: Pulling on the
      ECM resulted in initial cell elongation, followed by disengagement and retraction
      of pseudopodia. In contrast, pushing the ECM toward a cell induced rapid
      shortening (contraction), presumably since existing cellular forces were no
      longer counterbalanced by ECM tension. Pseudopodial extension (spreading) was
      then observed at both ends of the cell. The ECM was pulled inward during this
      secondary spreading, and rapid turnover of focal adhesions was observed along
      extending pseudopodia. Preincubation with Y-27632 or cytochalasin D blocked both
      the initial contractile and secondary spreading responses. CONCLUSIONS: Overall,
      the data suggest that corneal fibroblasts actively respond to increases or
      decreases in local matrix stress in an attempt to maintain tensional homeostasis
      (constant tension), and that this response may be mediated by Rho and/or Rac.

PMID- 15452052
TI  - Microarray studies reveal macrophage-like function of stromal keratocytes in the
      cornea.
AB  - PURPOSE: To elucidate biological processes underlying the keratocyte, fibroblast,
      and myofibroblast phenotypes of corneal stromal cells, the gene expression
      patterns of these primary cultures from mouse cornea were compared with those of
      the adult and 10-day postnatal mouse cornea. METHODS: Murine Genome_U74Av2 arrays
      (Affymetrix Inc., Santa Clara, CA) were used to elucidate gene expression
      patterns of adult and postnatal day-10 corneal stroma, keratocytes, fibroblasts,
      and myofibroblasts. RESULTS: Mobilization of stromal cells by culturing led to a
      wound-healing cascade in which specific extracellular matrix and cornea
      transparency-related genes were turned off, and a repertoire of macrophage genes
      were switched on. Thus, novel transparency-related crystallins detected in the
      corneal gene expression patterns were downregulated in culture, whereas
      macrophage genes, mannose receptor type-1, Cd68, serum amyloid-A3, chemokine
      ligands (Ccl2, Ccl7, Ccl9), lipocalin-2, and matrix metalloproteinase-3 and -12
      of innate immunity were induced in primary keratocyte cultures. Fibroblasts
      expressed the growth-related genes lymphocyte antigen 6 complex locus-A and
      preprokephalin-1, and myofibroblasts expressed annexin-A8, WNT1-inducible
      signaling pathway protein-1, arginosuccinate synthetase-1, and procollagen XI of
      late-stage wound healing. CONCLUSIONS: The emergent biological process suggests a
      dual role for resident stromal keratocytes in the avascular cornea: one of cornea
      maintenance, which involves synthesis of proteins related to the extracellular
      matrix and corneal transparency, and a second of barrier protection macrophage
      functions, which are switched on during corneal infection and injury.

PMID- 15452053
TI  - HGF protects corneal epithelial cells from apoptosis by the PI-3K/Akt-1/Bad- but
      not the ERK1/2-mediated signaling pathway.
AB  - PURPOSE: Cell survival is critical during corneal epithelial regeneration after
      injury, and growth factors could be fundamental in cytoprotection. The goal of
      this study was to investigate the involvement of the paracrine hepatocyte growth
      factor (HGF) in the prevention of corneal epithelial cell apoptosis and to
      identify signal transducers in this process. METHODS: Apoptosis in human and
      rabbit corneal epithelial (HCE and RCE) cells was induced with a nutrient
      deprived exhausted medium (ExM) or by treatment with staurosporine (20-100 ng/mL)
      or the calcium ionophore A23187 (0.5 microM). Apoptotic cells were identified by
      DNA fragmentation in agarose gels and by Hoechst staining. Active Akt-1
      overexpression (Akt-1 pUSEamp cDNA) and small interfering RNA (siRNA) specific
      for Akt mRNA were used. Immunofluorescence, Western immunoblot analysis, and Akt
      kinase assays were also used. RESULTS: Staurosporine, ExM, and A23187 induced DNA
      fragmentation in HCE and RCE cells. HGF (20 ng/mL) in combination with the
      apoptotic agents greatly reduced DNA breakdown and the number of Hoechst-positive
      cells. In the presence of phosphatidylinositol-3 kinase (PI-3K) inhibitors
      (wortmannin and LY294002), HGF did not overcome apoptosis. However, PD98059, the
      ERK1/2 cascade pathway inhibitor, was ineffective in preventing HGF protection.
      HGF induced a sustained activation of Akt-1, and overexpression of active Akt-1
      reduced apoptosis. HGF stimulated the downstream targets of Akt, glycogen
      synthase kinase (GSK-3), and Bad, a proapoptotic member of the Bcl-2 family, an
      effect that was blocked by PI-3K inhibitors but not by ERK1/2 inhibition.
      Suppressing the expression of Akt by Akt siRNA led to a decrease in the
      phosphorylation of Bad and GSK-3. Translocation of Bad to the mitochondria, a
      critical stage in apoptosis, was prevented by HGF when apoptosis was induced.
      Moreover, in epithelial cells overexpressing active Akt-1, Bad translocation was
      also prevented. CONCLUSIONS: HGF modulates multiple signaling cascades in corneal
      epithelial cells. The results demonstrated that HGF, in a paracrine fashion,
      protects cells from apoptosis through a PI-3K/Akt/Bad pathway but not through an
      ERK1/2 pathway. It was also demonstrated that GSK-3 is a target of PI-3K/Akt-1.

PMID- 15452054
TI  - Objective measurements of corneal light-backscatter during corneal swelling, by
      optical coherence tomography.
AB  - PURPOSE: To demonstrate that corneal light-backscatter can be measured
      objectively during corneal swelling by optical coherence tomography (OCT).
      METHODS: One eye (randomly selected) of 20 non-contact-lens wearers (10 men and
      10 women; mean age, 35.6 +/- 9.6 years) was patched during 3 hours of soft
      contact lens (SCL) wear. The contralateral eye acted as the control. Central
      corneal images were captured before and after SCL wear at 20-minute intervals
      over 100 minutes using optical coherence tomography (OCT) to obtain corneal
      thickness and light-backscatter profiles. OCT backscattered light of the
      epithelial layer (decided by the thickness measurements) and 10 equally divided
      layers of the remaining cornea were analyzed with a custom software program. Two
      baseline measurements were taken at different visits before lens wear to test the
      repeatability of light-backscatter measurements. RESULTS: From two baseline
      measurements, repeated measurements showed good repeatability of normalized
      backscatter results. Immediately after contact lens removal, total central
      corneal thickness increased significantly by 13.8% +/- 2.3% (mean +/- SD)
      compared with baseline (P = 0.0001, paired t-test) and then decreased during the
      deswelling course. Corneal backscattered light changed significantly (repeated
      measures ANOVA [Re-ANOVA]: F((50, 950)) = 2.22, P = 0.0001) after lens wear, and
      a significant increase in backscatter was found in the epithelial layer (36.4%)
      and the most posterior corneal layer (35.6%) immediately after lens removal (post
      hoc test, P = 0.005). There was a strong correlation (r = 0.9375, P < 0.05)
      between the change in backscatter and corneal swelling during the deswelling
      period. The backscatter recovery rate was approximately the same for both
      epithelial and posterior layers after lens removal. CONCLUSIONS: Light
      backscattering analysis with OCT seems to be a promising and repeatable method of
      objectively measuring corneal backscatter. This study has demonstrated that
      corneal backscattered light increased in the anterior and posterior layers of the
      cornea during corneal swelling induced by contact lens wear and eye closure.

PMID- 15452055
TI  - Role of keratocyte loss on corneal wound repair after LASIK.
AB  - PURPOSE: To investigate whether an initial keratocyte loss intensifies central
      corneal wound repair after LASIK in rabbits. METHODS: New Zealand White rabbits
      received either conventional LASIK (-8 D, 6-mm diameter) or LASIK combined with a
      7-mm diameter, epithelial denudation (LASIK-scrape). Animals were examined during
      4 months by slit lamp and in vivo confocal microscopy to monitor changes in
      central corneal morphology, light backscattering (haze), and sublayer thickness.
      At various time points, corneas were processed for histology and stained for
      nuclei; F-actin; ED-A fibronectin; alpha-smooth muscle actin; TGF-beta1, -beta2,
      and -beta receptor II; and connective tissue growth factor (CTGF). RESULTS: In
      vivo confocal microscopy identified no major acellular zones or changes in cell
      morphology or reflectivity after conventional LASIK. By contrast, a complete loss
      of keratocytes was observed in the anterior 77 +/- 25 microm stroma 1 week after
      LASIK-scrape. Highly reflective, migratory fibroblasts gradually repopulated the
      acellular zone, and by week 8, quiescent-appearing keratocytes were observed
      throughout the stroma. Correspondingly, stromal light backscattering peaked at 2
      weeks after LASIK-scrape (2200 +/- 620 U) followed by a decline to approximately
      60 U from week 8; comparable to the slightly increased reflectivity
      (approximately 50 U) observed after conventional LASIK (ns). Stromal thickness
      appeared stable 8 weeks after both LASIK and LASIK-scrape, after a regrowth of 13
      +/- 3 and 20 +/- 11 microm, respectively (ns). In addition, both procedures
      induced a minor and comparable epithelial hyperplasia of 4 +/- 2 and 7 +/- 5
      microm, respectively (ns). No myofibroblast transformation or TGF-beta growth
      factor expression was observed below the flap after either treatment.
      CONCLUSIONS: LASIK-scrape induces an anterior keratocyte loss, leading to
      development of temporary haze during cell repopulation. However, 8 weeks after
      both LASIK and LASIK-scrape, only a slightly increased reflectivity is noted at
      the interface. Corneal thickness is stable by week 8, and stromal regrowth and
      epithelial hyperplasia are comparable after both treatments. Thus, an initial
      loss of stromal keratocytes does not appear to intensify corneal wound repair
      after LASIK.

PMID- 15452056
TI  - Calcium-induced abnormal epidermal-like differentiation in cultures of mouse
      corneal-limbal epithelial cells.
AB  - PURPOSE: To develop a reproducible method for expanding mouse corneal-limbal
      epithelial cells and determine the role of extracellular Ca(2+) concentration and
      serum in modulating their growth and differentiation. METHODS: Intact and viable
      corneal epithelial sheets were isolated from CD-1 albino mouse eyeballs by
      incubating for 18 hours at 4 degrees C in 15 mg/mL dispase II with sorbitol in
      defined keratinocyte serum-free medium (KSFM) or supplementary hormonal
      epithelial medium (SHEM). These sheets were trypsinized into single cells and
      cultured on plastic in KSFM or SHEM. Cultures in KSFM were further manipulated by
      increasing Ca(2+) concentration to 0.9 mM, with or without 5% FBS. Epithelial
      growth was compared in KSFM/KSFM (digestion medium/culture medium) and SHEM/SHEM
      by continuous passaging at a 1:3 split and by crystal violet staining of
      confluent dishes. Epithelial differentiation was assessed by immunostaining
      and/or immunoblotting to ZO-1, cytokeratin K12 (K12), connexin 43 (Cx43),
      cytokeratin K10 (K10), and involucrin. RESULTS: Intact and viable corneal-limbal
      epithelial sheets were consistently isolated from more than 200 mouse eyes.
      Gradual increases in cell sizes and expression of ZO-1, K12, and Cx43 were noted
      from KSFM/KSFM to SHEM/KSFM, KSFM/SHEM, and SHEM/SHEM at passage 0. Epithelial
      growth ended at passage 1 in SHEM/SHEM but continued until passage 3 in
      KSFM/KSFM. Immunoblot analysis revealed that K12 expression was the highest in
      SHEM/SHEM, decreased from passages 0 to 1, and disappeared in passage 2 in
      KSFM/KSFM, with complete replacement of K10 and increasing expression of
      involucrin. Appearance of K10 was facilitated by 0.9 mM Ca(2+) but suppressed by
      5% FBS in KSFM at passage 0. CONCLUSIONS: Mouse corneal-limbal epithelial sheets
      can be used for initiating primary cultures, and their differentiation is
      promoted, whereas growth is suppressed, by a high Ca(2+) concentration, even
      during enzymatic digestion. In serum-free medium, abnormal epidermal-like
      differentiation is promoted by increasing Ca(2+) concentrations but prevented by
      serum. These results provide the ability to devise a medium to promote growth
      while maintaining normal differentiation.

PMID- 15452058
TI  - Refractive index change in bovine and human corneal stroma before and after
      lasik: a study of untreated and re-treated corneas implicating stromal hydration.
AB  - PURPOSE: To measure the refractive index (RI) of the mammalian corneal stroma in
      relation to hydration in vitro and human corneal stroma before and after LASIK.
      METHODS: RI at the anterior stromal surface of bovine corneal buttons was
      measured after the epithelium was scraped away. Samples were weighed and oven
      dried to calculate hydration. RI of the stromal bed surface was measured with a
      modified hand-held Abbe refractometer immediately before and after excimer laser
      photoablation. Thirty-one untreated persons (group 1: 44 corneas; age range, 19
      65 years) and eight re-treated patients (group 2: 10 corneas) were examined.
      RESULTS: RI of bovine stromal surface was significantly associated with hydration
      (H) (RI = 1.4067 - 0.00599H, r = -0.9079, P < 0.001). Photoablation significantly
      increased the RI of the midstroma (group 1: 1.3721 +/- 0.0041 to 1.3839 +/-
      0.0050; group 2: 1.3717 +/- 0.0038 to 1.3819 +/- 0.0039). Differences between
      groups were not significant. In group 1 (n = 31), change in RI (DeltaRI) was
      significantly related to preoperative RI (DeltaRI = 1.155 - 0.833RI, r = 0.595, P
      < 0.001) and RI was significantly related to age (x) (RI = 1.3634 + 0.00026x, r =
      0.603, P < 0.001). CONCLUSIONS: Mammalian corneal stromal RI correlates with
      hydration. LASIK significantly increases the refractive index of the treated
      stromal bed, and this equates to an average change in hydration from 4.3 to 2.9.
      For individual cases, change in RI is associated with the pre-op RI. The lack of
      any difference between untreated and re-treated corneas suggests that with time
      hydration returns back to normal levels. The RI in the older corneal stroma is
      slightly higher relative to the RI in the younger corneal stroma.

PMID- 15452057
TI  - Innate immune response of corneal epithelial cells to Staphylococcus aureus
      infection: role of peptidoglycan in stimulating proinflammatory cytokine
      secretion.
AB  - PURPOSE: This study sought to elucidate the innate immune responses of cultured
      human corneal epithelial cells (HCECs) to infection by the Gram-positive
      bacterium Staphylococcus aureus and to determine the underlying mechanisms.
      METHODS: HUCL, a telomerase-immortalized HCEC line, and primary cultures of HCECs
      were challenged with live or heat-killed S. aureus, its exoproducts, or cell wall
      components lipoteichoic acid (LTA) and peptidoglycan (PGN). IkappaB-alpha
      phosphorylation and degradation as well as phosphorylation of MAPKs, p38, and JNK
      1/2, were assessed by Western blot analysis. The expression of interleukin (IL)
      6, IL-8, TNF-alpha, and beta-defensin-2 were determined using RT-PCR and
      secretion of IL-6, IL-8, TNF-alpha, and beta-defensin were measured using enzyme
      linked immunosorbent assay and immunoblot analysis of culture medium. RESULTS:
      Exposure of HUCL cells to live, but not heat-killed, S. aureus resulted in NF
      kappaB activation in a time-dependent manner, as assessed by the increase in
      IkappaB-alpha phosphorylation and degradation. Live bacteria also activated the
      p38 and JNK pathways. The effects of live bacteria on HUCL cells may be
      attributable to bacterial exoproducts, since the conditioned medium of S. aureus
      also effectively stimulated these signaling pathways. PGN, but not LTA, activated
      the NF-kappaB and MAPK pathways in a dose- and time-dependent manner. Concomitant
      with activation of NF-kappaB and MAPKs, transcriptional expression of IL-6, IL-8,
      TNF-alpha, and beta-defensin-2 were induced in cells challenged with bacterial
      exoproducts and PGN. Secretion of IL-6, IL-8, TNF-alpha, and beta-defensin-2 were
      also significantly increased in HCECs in response to bacterial exoproducts and
      PGN challenge. CONCLUSIONS: Corneal epithelial cells possess the ability to
      recognize the presence of Gram-positive bacteria and to initiate the innate
      immune responses by the expression and/or release of proinflammatory cytokines
      and beta-defensin-2 in the cornea.

PMID- 15452059
TI  - Spatial-frequency-dependent changes in cortical activation before and after
      patching in amblyopic children.
AB  - PURPOSE: To examine the cortical response under transient stimulus conditions in
      amblyopic children before and after eye patching. To determine whether
      improvement in acuity is associated with spatial-frequency-dependent changes in
      specific peaks of the cortical response. METHODS: Visual evoked potentials (VEPs)
      to check reversal (163-18 arc min) and onset of sine wave gratings (0.5-4
      cyc/deg) were measured in 24 amblyopic children (<7 years of age) before eye
      patching. VEPs were repeated in nine subjects with 20/40 or better acuity after
      patching. Age, severity of amblyopia, and VEP amplitudes of positive peak (P)100,
      P1, and negative peak (N)2 were analyzed by multivariate statistics. RESULTS:
      Before patching, the amblyopic eye showed decreasing amplitude with increasing
      spatial frequencies (P < 0.05) when compared with the nonamblyopic eye. Reduced
      amplitudes occurred at frequencies well below acuity. Latencies were mildly
      prolonged. After patching, amplitudes increased in the amblyopic eye across all
      spatial frequencies (ANCOVA; P < 0.0001 for each peak). However, a spatial
      frequency-dependent increase in amplitude was significant only for a late
      negative peak (N2). The patched eye showed no significant changes. CONCLUSIONS:
      Recovery of acuity after eye patching is associated with an overall increase in
      cortical activation across a wide range of spatial frequencies below the acuity
      threshold. A spatial-frequency-dependent increase in a late negative peak
      suggests that the cortical generator of this peak demonstrates plasticity of
      acuity recovery.

PMID- 15452060
TI  - Role of exogenous and endogenous trophic factors in the regulation of extraocular
      muscle strength during development.
AB  - PURPOSE: Weak eye muscles can cause ophthalmic disorders, and in particular,
      strabismus. Exogenous trophic factors such as cardiotrophin (CT)-1 and insulin
      like growth factor (IGF) have been shown to increase the contractile force of
      adult heart and skeletal muscles, respectively. In the current study, the effects
      of endogenous and exogenous trophic factors on extraocular muscle strength and
      mass were examined in the developing chicken. METHODS: Superior rectus and
      superior oblique muscles of hatchling chicks were treated in vivo either to
      increase levels of trophic factors CT-1, IGF-I, glial cell line-derived
      neurotrophic factor (GDNF), or brain-derived neurotrophic factor (BDNF), or to
      decrease their levels with neutralizing antibodies and binding proteins. Forty
      eight hours after factors were injected into the orbit, the contractile force of
      dissected muscles was measured in vitro and the morphology of muscle fibers was
      compared between control and treated muscles. RESULTS: Treatment with CT-1 or IGF
      I significantly increased the mean single-twitch force generation and these
      trophic factors increased muscle fiber diameters when compared to control
      muscles. A cocktail of antibodies and binding proteins, directed against
      endogenous IGF-I, GDNF, and CT-1, significantly decreased mean single-twitch
      force. This cocktail slightly, but significantly, reduced muscle fiber diameters
      within treated extraocular muscles. CONCLUSIONS: Endogenous trophic factors
      regulate and/or maintain extraocular muscle force through a rapid mechanism that
      appears to involve changes in muscle mass and specifically enlargement of muscle
      fiber diameters. CT-1 and IGF-I may be considered promising candidate trophic
      factors for therapeutic strengthening of eye muscles in the developing
      extraocular muscle system.

PMID- 15452061
TI  - Abnormal systemic and ocular vascular response to temperature provocation in
      primary open-angle glaucoma patients: a case for autonomic failure?
AB  - PURPOSE: To assess systemic and ocular vascular reactivity in response to warm
      and cold provocation in untreated patients with primary open-angle glaucoma and
      normal control subjects. METHODS: Twenty-four patients with primary open-angle
      glaucoma and 22 normal control subjects were subjected to a modified cold pressor
      test involving immersion of the right hand in 40 degrees C warm water followed by
      4 degrees C cold water exposure, and finger and ocular blood flow were assessed
      by means of peripheral laser Doppler flowmetry and retinal flowmetry,
      respectively. Finger and body temperature as well as intraocular pressure,
      systemic blood pressure, systemic pulse pressure, heart rate, and ocular
      perfusion pressure were also monitored. RESULTS: The patients with glaucoma
      demonstrated an increase in diastolic blood pressure (P = 0.023), heart rate (P =
      0.010), and mean ocular perfusion pressure (P = 0.039) during immersion of the
      tested hand in 40 degrees C water. During cold provocation, the patients
      demonstrated a significant decrease in finger (P = 0.0003) and ocular blood flow
      (the parameter velocity measured at the temporal neuroretinal rim area; P =
      0.021). Normal subjects did not demonstrate any blood flow or finger temperature
      changes during immersion of the tested hand in 40 degrees C water (P > 0.05);
      however, they exhibited increases in systolic blood pressure (P = 0.034) and
      pulse pressure (P = 0.0009) and a decrease in finger blood flow (P = 0.0001)
      during cold provocation. In normal subjects, the ocular blood flow was unchanged
      during high- and low-temperature challenge. CONCLUSIONS: Cold provocation elicits
      a different blood pressure, and ocular blood flow response in patients with
      primary open-angle glaucoma compared with control subjects. These findings
      suggest a systemic autonomic failure and ocular vascular dysregulation in POAG
      patients.

PMID- 15452062
TI  - Effect of latanoprost on intraocular pressure in mice lacking the prostaglandin
      FP receptor.
AB  - PURPOSE: To determine whether latanoprost lowers IOP in prostaglandin FP receptor
      knockout mice. METHODS: Mean IOP difference between treated and untreated fellow
      eyes was measured on three separate occasions, 2 hours after a 200-ng dose of
      latanoprost to the right eye of homozygous (n = 9) and heterozygous (n = 15) FP
      knockout mice. C57BL/6 (n = 10) and NIH Swiss white mice (n = 17), which have
      normal FP receptor expression, provided the control population. The investigator
      was masked to the genotype of the FP knockout mice at the time of IOP
      measurement. RESULTS: Latanoprost had no effect on IOP in the homozygous FP
      knockout mice, with an average difference in IOP between treated and untreated
      fellow eyes of +0.25 mm Hg and a 95% confidence interval (CI) for the difference
      between means of -0.019 to +0.69. In contrast, latanoprost reduced IOP in the
      treated eye of the heterozygous FP knockout, C57BL/6, and Swiss white mice with
      mean differences and 95% CI of the difference in means of -0.52 (-0.91 to -0.14),
      -1.38 (-2.1 to -0.70), and -1.29 (-1.78 to -0.79) mm Hg, respectively.
      CONCLUSIONS: FP receptor signaling plays a crucial role in the early IOP response
      to latanoprost in the mouse eye.

PMID- 15452063
TI  - Intracellular sequestration of hetero-oligomers formed by wild-type and glaucoma
      causing myocilin mutants.
AB  - PURPOSE: To investigate mechanism(s) by which mutations in the olfactomedin
      domain of myocilin (MYOC), also known as the trabecular meshwork-induced
      glucocorticoid response (TIGR) gene, cause autosomal dominant open-angle
      glaucoma, the structure and properties of wild-type (WT) MYOC protein were
      examined, when expressed alone or simultaneously with the Q368X or K423E disease
      associated polypeptides. METHODS: Myocilin was analyzed in human aqueous humor
      and human trabecular meshwork (HTM) tissues. COS-7 and immortalized human
      trabecular meshwork (iHTM) cell lines were transfected with expression vectors
      encoding WT MYOC, mutated, and/or epitope-tagged cDNAs. MYOC proteins were
      characterized by double-epitope tagging procedures and/or Western blot analysis.
      RESULTS: MYOC polypeptides formed highly similar oligomers in aqueous humor, HTM
      tissues, transfected COS-7, and iHTM cell lines. These complexes ranged in size
      from 116 kDa to more than 200 kDa. The smallest complex, approximately 116 kDa,
      resulted from dimerization between two MYOC monomers. Expression of a 150-kDa
      complex was strongest in aqueous humor. Cotransfections of the WT construct with
      either the Q368X or K423E cDNA produced MYOC(WT)/MYOC(mutant) heterodimers and
      higher molecular weight hetero-oligomeric complexes. WT homo-oligomeric complexes
      were secreted in the extracellular media of both cell lines whereas the Q368X and
      K423E mutant/mutant homomultimers and heteromeric WT/mutant oligomers remained
      sequestered intracellularly. CONCLUSIONS: Formation of heteromeric WT/mutant
      complexes may provide a critical mechanism by which mutant myocilin polypeptides
      produce autosomal dominant open-angle glaucoma. The intracellular sequestration
      of abnormal WT/mutant complexes could lead to the malfunction of MYOC-expressing
      cells and to POAG potentially involving a dominant negative effect.

PMID- 15452064
TI  - Role of eIF5A in TNF-alpha-mediated apoptosis of lamina cribrosa cells.
AB  - PURPOSE: To determine the role of eukaryotic translation initiation factor 5A
      (eIF5A) in TNF-alpha-induced apoptosis of lamina cribrosa (LC) cells. METHODS: LC
      cells were isolated from optic nerve heads of eyes of two human donors. The cells
      were treated with TNF-alpha and camptothecin, a TNF synergist, and the incidence
      of apoptosis was scored by Hoechst staining. Expression of eIF5A protein in
      response to camptothecin or a combination of camptothecin and TNF-alpha was
      determined by Western blot analysis. The ability of small inhibitory (si)RNAs
      directed against eIF5A to protect LC cells from TNF-alpha-induced apoptosis was
      determined by Hoechst and TUNEL staining of transfected LC cells. RESULTS: TNF
      alpha and camptothecin synergized to induce greater than two times more apoptosis
      in LC cells than when the cells were treated with TNF-alpha or camptothecin
      separately. Expression of eIF5A protein increased significantly after 8 hours of
      exposure to TNF-alpha and camptothecin, but not in response to camptothecin
      alone. siRNAs directed against eIF5A reduced apoptosis of LC cells in response to
      TNF-alpha and camptothecin by between 35% and 69%, as determined by Hoechst
      staining. An siRNA against glyceraldehyde-3-phosphate dehydrogenase (GAPDH) also
      reduced apoptosis of LC cells by 42%. TUNEL of transfected LC cells treated with
      TNF-alpha and camptothecin revealed an 80% reduction in apoptosis with siRNA
      against eIF5A. CONCLUSIONS: TNF-alpha, in synergy with camptothecin, induces
      apoptosis in human LC cells. eIF5A is upregulated by LC cells in response to TNF
      alpha, and siRNAs against eIF5A protect LC cells from apoptosis. Thus, eIF5A
      appears to be a novel proapoptotic protein in the TNF pathway and a possible
      target for treatment of glaucoma.

PMID- 15452065
TI  - Phosphatidylinositol 3-kinase (PI-3K)/Akt but not PI-3K/p70 S6 kinase signaling
      mediates IGF-1-promoted lens epithelial cell survival.
AB  - PURPOSE: To investigate the ability of insulin-like growth factor (IGF)-1 to
      prevent apoptosis in lens epithelial cells and the involvement of
      phosphatidylinositol 3-kinase (PI-3K)/Akt and PI-3K/p70 S6 kinase (p70 S6K)
      signaling in the cell-survival process. METHODS: Apoptosis in rabbit lens
      epithelial cell cultures was induced by staurosporine (10 ng/mL). Cellular
      apoptosis was detected by identifying the characteristic ladder-like
      fragmentation of genomic DNA in agarose gels and the intense blue fluorescence
      exhibited by apoptotic nuclei of cells in live cultures in the presence of
      Hoechst 33,258 dye. Proliferation of lens epithelial cells grown in culture was
      measured with a DNA-binding fluorescent dye. Overexpression of the constitutively
      active Akt (CA-Akt) in epithelial cells was achieved by the transfection of cells
      using Fugene 6 reagent with a plasmid carrying Akt cDNA. Western immunoblotting
      was performed to identify various proteins of interest. RESULTS: IGF-1 (5 to 50
      nM) and insulin (100 to 400 nM) suppressed lens epithelial cell apoptosis in a
      dose-dependent manner, as determined by a significant inhibition of genomic DNA
      fragmentation and the decreased number of intense blue fluorescent Hoechst stain
      positive apoptotic nuclei in live cultures. DNA degradation was almost completely
      inhibited in the presence of 50 nM IGF-1 or 400 nM insulin. PI-3K inhibitors
      wortmannin and LY294002 blocked the IGF-1 effect on cell survival. Stimulation of
      lens epithelial cells with IGF-1 for 10 minutes to 24 hours resulted in the
      sustained activation of both Akt and p70 S6K. IGF-1 also induced the
      phosphorylation of Bad (a pro-apoptotic protein of the Bcl-2 family), which was
      inhibited by PI-3K inhibitors, but not by the p70 S6K inhibitor rapamycin.
      Furthermore, activation of Akt but not p70 S6K signaling by IGF-1 resulted in the
      inhibition of caspase-3 endogenous substrate poly (ADP-ribose) polymerase (PARP)
      degradation and apoptosis. The overexpression of CA-Akt in lens epithelial cells
      inhibited PARP breakdown and suppressed apoptosis. Inhibition of p70 S6K
      activation by rapamycin blocked IGF-1-promoted lens epithelial cell proliferation
      but not the cell-survival effect. CONCLUSIONS: These studies demonstrated a role
      for IGF-1 in the prevention of the lens epithelial cell apoptosis process.
      Furthermore, these studies indicated that anti-apoptotic and proliferative
      signals from IGF-1 bifurcate downstream of PI-3K. Whereas IGF-1-mediated PI
      3K/Akt signaling plays a pivotal role in cell survival by inactivating
      proapoptotic Bad protein and suppressing caspase activation, its stimulation of
      the PI-3K/p70 S6K cascade promotes proliferation.

PMID- 15452066
TI  - Ectopic Pax6 expression disturbs lens fiber cell differentiation.
AB  - PURPOSE: Pax6 is a transcription factor necessary for the specification and
      subsequent formation of the ocular lens. It is expressed in all lens cells at
      early stages of development. After lens formation, Pax6 expression is maintained
      in the lens epithelium, whereas its level abruptly decreases in differentiated
      fiber cells. This study is to test the hypothesis that normal fiber cell
      differentiation would be perturbed by sustained Pax6 expression. METHODS:
      Transgenic mice expressing the canonical form of mouse Pax6 were created under
      the control of a modified mouse alphaA-crystallin promoter. The phenotypic
      changes in the transgenic lens were analyzed by light and electron microscopy.
      The effect of ectopic Pax6 expression on the lens fiber cells was investigated by
      in situ hybridization, immunohistochemical staining, real-time reverse
      transcriptase-polymerase chain reaction (RT-PCR), and two-dimensional (2-D) gel
      electrophoresis. RESULTS: Transgenic mice from seven different lines all had
      cataracts with severity that correlated with the transgene expression level in
      lens fiber cells. In severely affected lines, a lumen was present between the
      apical surfaces of the epithelial and fiber cells, suggesting that secondary
      fiber cell elongation is incomplete. Electron microscopy analysis showed that the
      ball-and-socket interdigitations between neighboring fiber cells were
      underdeveloped or attenuated in the transgenic lens. Most interesting, elevated
      levels of Pax6 in fiber cells reduced the protein levels of transcription factor
      cMaf, which is known to be essential in fiber cell differentiation. Furthermore,
      the total amount of lens proteins was 60% less than normal in the Pax6 transgenic
      lens. Among the crystallins examined, the relative ratio of intact betaB1
      crystallin protein to total lens protein was significantly reduced. Real-time
      reverse transcriptase PCR showed that the ratio of betaB1-crystallin transcript
      levels to total mRNA levels were reduced by 87%. CONCLUSIONS: The data
      demonstrate that high levels of Pax6 expression disrupt normal fiber cell
      differentiation and maturation.

PMID- 15452067
TI  - Mutation analysis of congenital cataracts in Indian families: identification of
      SNPS and a new causative allele in CRYBB2 gene.
AB  - PURPOSE: To study some functional candidate genes in cataract families of Indian
      descent. METHODS: Nine Indian families, clinically documented to have
      congenital/childhood cataracts, were screened for mutations in candidate genes
      such as CRYG (A-->D), CRYBB2, and GJA8 by PCR analyses and sequencing. Genomic
      DNA samples of either probands or any representative affected member of each
      family were PCR amplified and sequenced commercially. Documentation of single
      nucleotide polymorphisms (SNPs) and candidate mutations was done through BLAST
      SEARCH (http://www.ncbi.nlm.nih.gov/blast/Blast.cgi?). RESULTS: Several single
      nucleotide polymorphisms in CRYG, CRYBB2, and GJA8 genes were observed. Because
      they do not co-segregate with the phenotype, they were excluded as candidates for
      the cataract formation in these patients. However, a substitution (W151C in exon
      6 of CRYBB2) was identified as the most likely causative mutation underlying the
      phenotype of central nuclear cataract in all affected members of family C176.
      Protein structural interpretations demonstrated that no major structural
      alterations could be predicted and that even the hydrogen bonds to the
      neighboring Leu166 were unchanged. Surprisingly, hydropathy analysis of the
      mutant betaB2-crystallin featuring the amino acids at position 147 to 155,
      further increased the hydrophobicity, which might impair the solubility of the
      mutant protein. Finally, the Cys residue at position 151 might possibly be
      involved in intramolecular disulphide bridges with other cysteines during
      translation, possibly leading to dramatic structural changes. CONCLUSIONS: Exon 6
      of CRYBB2 appears to be a critical region susceptible for mutations leading to
      lens opacity.

PMID- 15452068
TI  - Expression and regulation of alpha-, beta-, and gamma-crystallins in mammalian
      lens epithelial cells.
AB  - PURPOSE: In the mammalian lens, the expression of the beta- and gamma-crystallin
      families is thought to be limited to fiber cells. However, several studies
      detected these proteins or their mRNAs in human lens epithelial cells. To resolve
      this apparent discrepancy, 14 crystallin mRNAs were examined and the expression
      and subcellular distribution of selected crystallin proteins in lens epithelial
      cells determined. METHODS: Transcript levels were analyzed by quantitative real
      time PCR using mRNA from P3 rat lens epithelia cultured for 0 or 20 hours or 4 or
      7 days in basal medium or with added FGF2. Antibodies to betaB1-, gammaS-, alphaA
      , and alphaB-crystallins were used for Western blot analysis of proteins
      extracted from adult mouse, human, bovine, rabbit, and rat lens epithelial and
      fiber cells. Rat lenses or lens epithelia were rapidly fixed in situ, 30 minutes
      after death, or after dissection from the lens, and the intracellular
      distributions of crystallins were examined by immunostaining and confocal
      microscopy. RESULTS: Four patterns of crystallin gene expression were detected in
      cultured lens epithelia. Transcripts encoding most beta- and gamma-crystallins
      were detectable and, in some cases, abundant at the time of explantation. Changes
      in crystallin protein levels in P3 epithelia cultured in basal or FGF
      supplemented medium generally reflected the changes in their mRNAs. betaB1- and
      gammaS-crystallins were abundant in adult human, mouse, rat, rabbit, and bovine
      lens epithelial cells. The alpha-, beta- and gamma-crystallins were found in
      distinct subcellular locations in adult lens epithelial cells. These proteins
      dramatically relocalized during fiber cell differentiation and after death and/or
      dissection of the lens epithelium. CONCLUSIONS: BetaB1- and gammaS-crystallins
      are normally abundant in adult mammalian lens epithelial cells. Complex programs
      of transcription and degradation regulate the accumulation of crystallin mRNAs in
      lens epithelial cells after stress, at different ages, and during cell
      differentiation. Because crystallins selectively localize in distinct subcellular
      compartments during differentiation or stress, they may function to protect lens
      cells from injury. After stress, most alphaA- and alphaB-crystallin subunits are
      not in the same macromolecular complexes.

PMID- 15452069
TI  - Effects of pirenzepine on pupil size and accommodation in rhesus monkeys.
AB  - PURPOSE: Pirenzepine is suggested to be a relatively selective muscarinic (M(1))
      antagonist and is currently under investigation for the treatment of myopia.
      Atropine, a nonselective M-type antagonist, is used in the treatment of myopia,
      but has undesired ocular and systemic side effects. An M(1)-specific antagonist
      may decrease side effects and remain effective at reducing the progression of
      myopia. In the current study, the effects of pirenzepine on pupil diameter,
      resting refraction, and accommodation were studied in rhesus monkeys. METHODS:
      The time course and extent of mydriasis from subconjunctival injection of 2%
      pirenzepine were determined in five normal rhesus monkeys, and the effects on
      static and dynamic accommodation were determined in four rhesus monkeys with
      permanent indwelling electrodes in the Edinger-Westphal (EW) nucleus of the
      midbrain. Subconjunctival injections of 0.0002% to 0.2% pirenzepine in log unit
      dilutions were tested in three monkeys to determine the effects on static EW
      stimulated accommodation. At 40 to 50 minutes after pirenzepine injection,
      accommodation was stimulated pharmacologically in both eyes, and the response was
      measured for 30 minutes. RESULTS: After 2% pirenzepine injection, pupil size
      increased 2.02 +/- 0.41 mm, there was a hyperopic shift in resting refraction of
      1.07 +/- 0.23 D, and nearly complete cycloplegia occurred. Maximum EW-stimulated
      accommodation was significantly decreased 20 to 40 minutes after 0.02% or greater
      pirenzepine. Carbachol-stimulated accommodation was significantly decreased after
      0.2% or greater pirenzepine. CONCLUSIONS: Subconjunctival injections of 0.02% or
      greater pirenzepine result in a significant decrease in accommodation and are
      probably acting through nonselective muscarinic antagonism. Subconjunctival
      injections of 0.002% or less pirenzepine do not decrease EW-stimulated
      accommodation.

PMID- 15452070
TI  - Lens gap junctional coupling is modulated by connexin identity and the locus of
      gene expression.
AB  - PURPOSE: To investigate the effects of reducing connexin (Cx) diversity in the
      lens when the amount of connexin protein is nearly constant. METHODS: Lenses in
      which the Cx50 coding region was replaced by that of Cx46 (knockin [KI]), were
      compared with wild type (WT) and Cx50-knockout (KO) lenses. Gap junctional
      conductance (G(j)), and membrane conductance were evaluated by using frequency
      domain impedance of intact lenses. RESULTS: KO of Cx50 produced small depolarized
      lenses with central opacities. KI of Cx46 did not restore growth, but rescued
      resting voltage and eliminated opacities. In WT lenses, the average G(j) was
      approximately 1 S/cm(2) of cell-to-cell contact in the outer shell of
      differentiating fibers (DFs), whereas it was approximately half that value in the
      core of mature fibers (MFs). KO of Cx50 reduced G(j) in DF to 44% of normal,
      whereas KI of Cx46 restored G(j) to approximately 60% of normal. In addition, KI
      of Cx46 markedly increased G(j) in MFs. In WT lenses, all gap junction channels
      in DFs close when pH is reduced, whereas those in MFs are insensitive to pH. KO
      of Cx50 made both DF and MF channels pH insensitive, whereas KI of Cx46 restored
      pH sensitivity of all DF channels without altering MF pH insensitivity
      CONCLUSIONS: Lens size and fiber cell coupling conductance depended on which
      connexin was expressed on the Cx50 gene locus, whereas homeostasis of central
      fibers and normal gap junction gating were maintained when either connexin was
      expressed. The authors conclude that the roles of lens gap junction channels
      depend not only on the primary sequence of the expressed connexin, but also on
      the gene locus that expresses the connexin.

PMID- 15452071
TI  - cAMP inhibits transepithelial chloride secretion across bovine ciliary
      body/epithelium.
AB  - PURPOSE: To investigate the potential significance of cAMP in the regulation of
      Cl(-) transport across the bovine ciliary body/epithelium (CBE). METHODS: Fresh
      native bovine CBE preparation was mounted in a modified Ussing chamber. The
      effects of cAMP-stimulating agents on short-circuit current (I(sc)) and net
      (36)Cl(-) secretion were determined. RESULTS: Addition of cAMP-stimulating agents
      inhibited net Cl(-) secretion. Forskolin, when added bilaterally, reduced Cl(-)
      secretion by 60%. Similarly, bilateral isoproterenol or vasoactive intestinal
      peptide inhibited Cl(-) transport by 15% and 37%, respectively, suggesting a cAMP
      sensitive Cl(-) transport across the ciliary epithelium. This notion was
      supported by the exogenous application of 8-bromo-cAMP (8-Br-cAMP) or 3-isobutyl
      1-methylxanthine (IBMX), which reduced the net Cl(-) secretion by 49% and 85%,
      respectively. In unstimulated preparations, addition of 5-nitro-2-(3
      phenylpropylamino)-benzoic acid (NPPB) to the blood side had no effects on I(sc)
      and net Cl(-) transport, indicating that Cl(-) reabsorption was negligible under
      baseline conditions. Also, pretreatment with NPPB from the blood side did not
      prevent forskolin-induced I(sc) inhibition, suggesting that the inhibition of Cl(
      ) transport did not result from the facilitation of Cl(-) reabsorption. However,
      pretreatment with heptanol from both sides completely blocked the forskolin
      induced I(sc) inhibition, suggesting that cAMP may reduce Cl(-) transport by
      uncoupling the intercellular gap junctions. CONCLUSIONS: The results suggest that
      cAMP plays a crucial role in modulating Cl(-) secretion across the ciliary
      epithelium. The effect is possibly mediated, at least in part, by the regulation
      of the permeability of gap junctions between pigmented and nonpigmented ciliary
      epithelial cells.

PMID- 15452072
TI  - Pharmacokinetics of systemic versus focal Carboplatin chemotherapy in the rabbit
      eye: possible implication in the treatment of retinoblastoma.
AB  - PURPOSE: To characterize the pharmacology and toxicity of intravenous versus
      focal carboplatin delivery in the rabbit eye. METHODS: Pharmacological
      distribution of carboplatin was examined in New Zealand White Rabbits after a
      single intravenous infusion of carboplatin (18.7 mg/kg of body weight), a single
      subconjunctival carboplatin injection (5.0 mg/400 microL), or a single
      application of carboplatin delivered by Coulomb-controlled iontophoresis (CCI; 14
      mg/mL carboplatin, 5.0 mA/cm(2), 20 minutes). After each treatment, animals were
      euthanatized, and the eyes analyzed at 1, 2, 6, or 24 hours by atomic absorption
      spectroscopy to determine carboplatin concentration in ocular structures.
      Potential toxicity of focally delivered carboplatin was assessed by histology
      after six cycles of 5.0 mg carboplatin delivered by subconjunctival injection or
      six transscleral carboplatin CCI applications at 72-hour intervals (14.0 mg/mL,
      20 minutes at 2.5 mA). RESULTS: Determination of concentrations through atomic
      absorption spectroscopy in the retina, choroid, vitreous humor, and optic nerve
      after subconjunctival injection or iontophoretic carboplatin delivery revealed
      significantly higher levels than those achieved with intravenous administration.
      Carboplatin concentrations in the blood plasma were found to be significantly
      higher after intravenous delivery than after focal delivery by subconjunctival
      injection or CCI. No evidence of ocular toxicity was detected after focally
      delivered Carboplatin. CONCLUSIONS: Focal administration of carboplatin using
      subconjunctival or noninvasive CCI safely and effectively transmits this
      chemotherapeutic drug into the target tissues of the retina, choroid, vitreous,
      and optic nerve. These results suggest that focal carboplatin delivery may
      effectively increase intraorbital carboplatin concentrations while decreasing
      systemic exposure to this cytotoxic drug.

PMID- 15452073
TI  - Modulation of aqueous humor outflow by ionic mechanisms involved in trabecular
      meshwork cell volume regulation.
AB  - PURPOSE: Trabecular meshwork (TM) cell shape, volume, contractility and their
      interactions with extracellular matrix determine outflow facility. Because cell
      volume seems essential to TM function, this study was conducted to investigate
      further the ionic channels and receptors involved in regulatory volume decrease
      and their roles in modulating outflow facility. METHODS: Primary cultures of
      bovine TM cells were used. K(+) and Cl(-) currents were studied with whole-cell
      patch clamping. Swelling was induced by hypotonic shock. [Ca(2+)](i) was measured
      in TM cells loaded with fura-2. Bovine anterior segments were perfused at
      constant pressure to measure outflow facility. RESULTS: Hypotonic media activated
      both the high-conductance Ca(2+)-activated K(+) channel (BK(Ca)) and swelling
      activated Cl(-) channel (Cl(swell)) currents and induced release of adenosine 5'
      triphosphate (ATP) from TM cells. ATP activated P2Y(2) receptors with the
      following profile: ATP = uridine 5'-triphosphate (UTP) > adenosine 5'-O-(3
      thiotriphosphate) (ATP-gamma S) > adenosine 5'-diphosphate (ADP) = uridine 5'
      diphosphate (UDP), and increased BK(Ca) current. Hypotonic medium initially
      decreased outflow facility in perfused anterior segments, which recovered with
      time to baseline levels. Addition of tamoxifen or iberiotoxin (Cl(swell) and
      BK(Ca) blockers, respectively) lengthened the recovery phase, which implies that
      these channels participate in cell volume regulation. In contrast, an activator
      of BK(Ca)s (NS1619) produced the opposite effect. CONCLUSIONS: Cell swelling
      activates a regulatory volume decrease mechanism that implies activation of K(+)
      and Cl(-) currents and participation of P2Y(2) receptors. Because previous
      studies have shown that intracellular volume of TM cells is an important
      determinant of outflow facility, it seems feasible that cell volume regulation
      would be part of the homeostatic mechanisms of the TM, to regulate the outflow
      pathway.

PMID- 15452074
TI  - Flicker-evoked response measured at the optic disc rim is reduced in ocular
      hypertension and early glaucoma.
AB  - PURPOSE: To determine in patients with ocular hypertension (OHT) or early
      glaucoma (EOAG) the change in blood flow measured at the neuroretinal rim of the
      optic disc in response to a 15-Hz diffuse green luminance flicker, a stimulus
      that activates predominantly the ganglion cell magnocellular pathway. METHODS:
      Thirteen patients with EOAG, 29 with OHT, and 16 age-matched control subjects,
      all with excellent fixation, were examined. Blood flow (F(onh)) at the
      neuroretinal rim of the optic disc was continuously monitored by laser Doppler
      flowmetry before and during exposure to a 15-Hz, 30 degrees field green luminance
      flicker. The response of F(onh) to this stimulus (RF(onh)) was expressed as
      percentage change in F(onh) between baseline and the last 20 seconds of flicker.
      Two to three temporal sites of the disc were tested, and the highest RF(onh) was
      considered for further analysis. RF(onh) results in patients were correlated with
      morphologic (cup-to-disc area ratio, cup shape neuroretinal rim area) and
      functional (perimetric mean deviation and pattern electroretinogram amplitude)
      clinical parameters. RESULTS: In the patients with OHT or EOAG, F(onh) and
      RF(onh) were both reduced compared with their respective values in the control
      group. Both quantities decreased significantly with neuroretinal rim area when
      the patients' data were pooled. No significant correlation was found between
      F(onh) or RF(onh) and the other morphometric and functional parameters. The group
      averaged time course of RF(onh) was not significantly different from that in the
      normal subjects. CONCLUSIONS: Luminance flicker-evoked RF(onh) is abnormally
      reduced in patients with OHT or EOAG, indicating an impairment of neurally
      mediated vasoactivity. The data suggest that PERG-derived neural activity and
      flicker-evoked RF(onh) can be independently altered early in the disease process.

PMID- 15452075
TI  - Experimental retinal vein occlusion: effect of acetazolamide and carbogen (95%
      O2/5% CO2) on preretinal PO2.
AB  - PURPOSE: To evaluate the variations of preretinal oxygen partial pressure (Po(2))
      in normal and in ischemic postexperimental branch retinal vein occlusion (BRVO)
      areas, during normoxia, hyperoxia (100% O(2)), and carbogen (95% O(2), 5% CO(2))
      breathing before and after intravenous injection of acetazolamide. METHODS:
      Preretinal Po(2) measurements were obtained in intervascular retinal areas,
      distant from the retinal vessels of 13 anesthetized mini-pigs with oxygen
      sensitive microelectrodes (10 microm tip diameter) introduced through the
      vitreous cavity by a micromanipulator. The microelectrode tip was placed <50
      microm from the vitreoretinal interface in the preretinal vitreous. Po(2) was
      measured continuously for 10 minutes under systemic normoxia, hyperoxia, and
      carbogen breathing. A BRVO was induced with an argon green laser, and oxygen
      measurements were repeated under normoxia, hyperoxia, and carbogen breathing,
      before and after intravenous injection of acetazolamide (500 mg bolus). RESULTS:
      In hyperoxia, a moderate nonsignificant preretinal Po(2) increase in both normal
      (DeltaPo(2) = 2.20 +/- 4.16 mm Hg; n = 25) and ischemic retinas (DeltaPo(2) =
      4.30 +/- 3.57 mm Hg; n = 16) was measured in spite of a substantial increase in
      systemic Pao(2). Carbogen breathing induced a significant increase in systemic
      Paco(2) and a higher systemic Pao(2) than hyperoxia. Furthermore, it
      significantly increased the preretinal Po(2) in normal areas (DeltaPo(2) = 19.37
      +/- 16.41 mm Hg; n = 26), and in ischemic areas (DeltaPo(2) = 14.94 +/- 8.53 mm
      Hg; n = 14). Intravenous acetazolamide did not affect the preretinal Po(2).
      Acetazolamide induced an increase of the preretinal Po(2) to a greater extent
      when it was associated with carbogen breathing (DeltaPo(2) = 15.15 +/- 9.15 mm
      Hg; n = 7) than when it was combined with hyperoxia (DeltaPo(2) = 6.96 +/- 4.49
      mm Hg; n = 7). CONCLUSIONS: Carbogen breathing significantly increased preretinal
      Po(2) in normal and in ischemic postexperimental BRVO areas of mini-pigs. The
      concomitant use of acetazolamide injection and carbogen breathing or hyperoxia
      could restore an appropriate oxygenation of BRVO areas.

PMID- 15452076
TI  - Retinal temperature increase during transpupillary thermotherapy: effects of
      pigmentation, subretinal blood, and choroidal blood flow.
AB  - PURPOSE: To study the risk of adverse events in transpupillary thermotherapy
      (TTT) for age-related macular degeneration by measuring how laser-induced retinal
      temperature increase is affected experimentally by subretinal blood, choroidal
      blood flow, and chorioretinal pigmentation. METHODS: An ultrafine thermocouple
      technique was developed to measure retinal temperature increase during TTT in
      albino and pigmented rabbit eyes. TTT was performed with 60-second, 0.78-mm spot
      size, 810-nm infrared diode laser exposures with power settings ranging from 50
      to 950 mW. Intraretinal and subretinal temperature increases were measured in
      pigmented and albino rabbits, with or without subretinal blood and choroidal
      blood flow. RESULTS: Threshold power settings for visible lesions in albino and
      pigmented rabbits were 950 and 90 mW, respectively, corresponding to retinal
      temperature increases of 11.8 degrees C and 5.28 degrees C, respectively. Power
      settings required to produce threshold lesions in albino rabbits caused retinal
      temperature increases in pigmented rabbits that were five times higher than in
      the albino rabbits. Temperature increases in albino rabbits were 1.5 times higher
      with subretinal blood than without it. Choroidal blood flow generally did not
      affect measured retinal temperature increases. CONCLUSIONS: The results confirm
      prior theoretical recommendations that clinicians should consider decreasing TTT
      power settings in darkly pigmented eyes and proceed with caution in those with
      subretinal hemorrhage or pigment clumping.

PMID- 15452077
TI  - Mutations of VMD2 splicing regulators cause nanophthalmos and autosomal dominant
      vitreoretinochoroidopathy (ADVIRC).
AB  - PURPOSE: To investigate the genetic basis of autosomal dominant
      vitreoretinochoroidopathy (ADVIRC), a rare, inherited retinal dystrophy that may
      be associated with defects of ocular development, including nanophthalmos.
      METHODS: A combination of linkage analysis and DNA sequencing in five families
      was used to identify disease-causing mutations in VMD2. The effect of these
      mutations on splicing was assessed using a minigene system. RESULTS: Three
      pathogenic sequence alterations in VMD2 were identified in five families with
      nanophthalmos associated with ADVIRC. All sequences showed simultaneous missense
      substitutions and exon skipping. CONCLUSIONS: VMD2 encodes bestrophin, a
      transmembrane protein located at the basolateral membrane of the RPE, that is
      also mutated in Best macular dystrophy. We support that each heterozygous
      affected individual produces three bestrophin isoforms consisting of the wild
      type and two abnormal forms: one containing a missense substitution and the other
      an in-frame deletion. The data showed that VMD2 mutations caused defects of
      ocular patterning, supporting the hypothesized role for the RPE, and specifically
      VMD2, in the normal growth and development of the eye.

PMID- 15452078
TI  - Hyperoxia promotes electroretinogram recovery after retinal artery occlusion in
      cats.
AB  - PURPOSE: This work assessed the hypotheses that (1) hyperoxia is preferable to
      air breathing during retinal arterial occlusion, (2) hyperoxia during occlusion
      is beneficial in promoting recovery from arterial occlusion, and (3) hyperoxia
      has value even if it is delayed relative to the onset of the occlusion. METHODS:
      Reversible branch retinal artery occlusion was produced by pressing with a glass
      probe onto an artery emerging from the superior part of the optic disc in the
      retina of anesthetized cats. During 2-hour occlusion episodes, the cats breathed
      100% O(2), 1 hour of air and 1 hour of 100% O(2), 1 hour of air and 1 hour of 70%
      O(2), or air. Intraretinal ERGs were recorded before, during, and after the
      occlusion. RESULTS: Hyperoxia during occlusion preserved intraretinal b-wave
      amplitude at 86% +/- 12% of normal; longer durations of increased oxygenation
      maintained the b-wave at higher levels during occlusion and increased the
      probability of b-wave recovery after occlusion; higher O(2) content in the
      breathing gas increased b-wave amplitude during recovery; and hyperoxia during
      occlusion decreased the time it took for the b-wave to recover after the
      occlusion. CONCLUSIONS: Hyperoxia is preferable to air breathing during retinal
      arterial occlusion not only for maintaining b-wave amplitude during occlusion,
      but also for providing a shorter recovery time and better percentage recovery
      after the end of the occlusion. Even if it is not possible to begin hyperoxia at
      the onset of occlusion, it may still be valuable.

PMID- 15452079
TI  - Safety testing of infracyanine green using retinal pigment epithelium and glial
      cell cultures.
AB  - PURPOSE: To undertake safety testing of infracyanine green (IFCG) in a cell
      culture model. METHODS: Experiments were undertaken in a cell culture model used
      previously to perform safety testing of indocyanine green (ICG). Human retinal
      pigment epithelium (RPE) and Muller cells were exposed to IFCG for 5 minutes,
      over a range of concentrations up to 0.5%. Experiments were repeated, using
      double-staining with trypan blue. Cell viability was measured at days 1, 5, and
      15 using a mitochondrial dehydrogenase assay and a fluorescent live-dead probe
      containing calcein and ethidium homodimer-1. Viability was measured after
      exposure to 0.5% IFCG and 5 minutes of illumination with a vitrectomy endolight
      powered by a xenon light source. RESULTS: RPE viability was not reduced over the
      range of concentrations and follow-up intervals. RPE cells exposed to IFCG and
      illumination had reduced viability relative to the negative control (cells
      exposed to saline), but not relative to those exposed to saline and illumination.
      Glial cells showed reduced viability at days 1 and 5, but not day 15.
      Illumination did not further reduce viability. CONCLUSIONS: IFCG has been
      advocated as a safer macular vital stain than ICG. These results suggest that it
      is less likely to produce phototoxicity, but despite being nearly iso-osmolar,
      IFCG also produces damage in cultured glial cells.

PMID- 15452080
TI  - Conditional knockdown of tubedown-1 in endothelial cells leads to neovascular
      retinopathy.
AB  - PURPOSE: Identification of novel proteins involved in retinal neovascularization
      may facilitate new and more effective molecular-based treatments for
      proliferative retinopathy. Tubedown-1 (Tbdn-1) is a novel protein that shows
      homology to the yeast acetyltransferase subunit NAT1 and copurifies with an
      acetyltransferase activity. Tbdn-1 is expressed in normal retinal endothelium but
      is specifically suppressed in retinal endothelial cells from patients with
      proliferative diabetic retinopathy. The purpose of this study was to investigate
      the importance of Tbdn-1 expression in retinal blood vessels in vivo. METHODS: A
      bitransgenic mouse model that enables conditional knockdown of Tbdn-1
      specifically in endothelial cells was produced and studied using molecular,
      histologic, and immunohistochemical techniques and morphometric analysis.
      RESULTS: Tbdn-1-suppressed mice exhibited retinal and choroidal
      neovascularization with intra- and preretinal fibrovascular lesions similar to
      human proliferative retinopathies. Retinal lesions observed in Tbdn-1-suppressed
      mice increased in severity with prolonged suppression of Tbdn-1. In comparison to
      normal retina, the retinal lesions displayed alterations in the basement membrane
      of blood vessels and in the distribution of glial and myofibroblastic cells.
      Moreover, the pathologic consequences of Tbdn-1 knockdown in endothelium were
      restricted to the retina and the choroid. CONCLUSIONS: These results indicate
      that the maintenance of Tbdn-1 expression is important for retinal blood vessel
      homeostasis and for controlling retinal neovascularization in adults. Restoration
      of Tbdn-1 protein expression and/or activity may provide a novel approach for
      treating proliferative retinopathies.

PMID- 15452081
TI  - Receptor for advanced glycation end products and age-related macular
      degeneration.
AB  - PURPOSE: Advanced glycation end products (AGE) exacerbate disease progression
      through two general mechanisms: modifying molecules and forming nondegradable
      aggregates, thus impairing normal cellular/tissue functions, and altering
      cellular function directly through receptor-mediated activation. In the present
      study receptor for AGE (RAGE)-mediated cellular activation was evaluated in the
      etiology of human retinal aging and disease. METHODS: The maculas of human donor
      retinas from normal eyes and eyes with early age-related macular degeneration
      (AMD) and advanced AMD with geographic atrophy (GA) were assayed for AGE and RAGE
      by immunocytochemistry. Cultured ARPE-19 cells were challenged with known ligands
      for RAGE, AGE, and S100B, to test for activation capacity. Immunocytochemistry,
      real-time RT-PCR, immunoblot analysis, and the TUNEL assay were used to determine
      the consequences of RPE cellular activation. RESULTS: Little to no immunolabeling
      for AGE or RAGE was found in photoreceptor and RPE cell layers in normal retinas.
      However, when small drusen were present, AGE and RAGE were identified in the RPE
      or both the RPE and photoreceptors. In early AMD and GA, the RPE and remnant
      photoreceptor cells showed intense AGE and RAGE immunolabeling. Both AGE and
      S100B activated cultured RPE cells, as revealed by upregulated expression of
      RAGE, NFkappaB nuclear translocation, and apoptotic cell death. CONCLUSIONS:
      Immunolocalization of RAGE in RPE and photoreceptors coincided with AGE deposits
      and macular disease in aged, early AMD, and GA retinas. Further, AGE stimulated
      RAGE-mediated activation of cultured ARPE-19 cells in a dose-dependent fashion.
      AGE accumulation, as occurs with normal aging and in disease, may induce receptor
      mediated activation of RPE/photoreceptor cells, contributing to disease
      progression in the aging human retinas.

PMID- 15452082
TI  - Photoreceptor protection by iris pigment epithelial transplantation transduced
      with AAV-mediated brain-derived neurotrophic factor gene.
AB  - PURPOSE: To determine whether subretinal transplantation of iris pigment
      epithelial (IPE) cells transduced with the adeno-associated virus (AAV2)-mediated
      brain-derived neurotrophic factor (BDNF) gene can protect photoreceptors against
      phototoxicity. METHODS: The BDNF gene was inserted into AAV2 (AAV2-BDNF), and the
      recombinant AAV2 was transduced into rat IPE (AAV2-BDNF-IPE) cells at various
      multiplicities of infection (MOI). The concentrations of AAV capsids and BDNF
      were determined by enzyme-linked immunosorbent assay (ELISA). The AAV2-BDNF-IPE
      cells were transplanted into the subretinal space of rats, and the rats were
      placed under constant light on days 1 and 90 after the transplantation. The
      thickness of the outer nuclear layer was measured in histologic sections and
      compared to that of control sections. The expression of beta-galactosidase (LacZ)
      in the subretinal space was confirmed by LacZ staining after AAV2-LacZ-IPE
      transplantation. BDNF gene expression after transplantation was confirmed by real
      time polymerase chain reaction (PCR). RESULTS: Transduction efficiency increased
      with successive days in culture and increased with higher MOI in vitro. The
      expression of the BDNF gene in the subretinal space was higher in AAV-BDNF-IPE
      than with AAV2-LacZ-IPE or with IPE-only transplantation. LacZ expression was
      observed in the subretinal space 7 and 90 days after transplantation. A
      statistically significant photoreceptor protection was observed on days 1 and 90
      in eyes receiving the AAV2-BDNF-IPE transplant, in both the superior transplant
      site and the inferior hemispheres which did not receive the transplant.
      CONCLUSIONS: Transplantation of AAV2-BDNF-IPE cells may be an alternative method
      of delivering neurotrophic factors to the lesion.

PMID- 15452083
TI  - Heme oxygenase-1-related carbon monoxide and flavonoids in ischemic/reperfused
      rat retina.
AB  - PURPOSE: There is increasing evidence to show cytoprotective effects of various
      flavonoid-rich extracts and the tissue-protective capacity of flavonoid-rich
      extract of sour cherry is due to flavonoid components of seeds. Sour cherry seed
      flavonoids were evaluated for their contribution to postischemic recovery related
      to endogenous carbon monoxide (CO) production in rat retinas subjected to
      ischemia/reperfusion. METHODS: Rats were orally treated with selected doses of
      flavonoid-rich extract of sour cherry seeds for 2 weeks. Animals were
      anesthetized, and a suture was placed behind the globe including the central
      retinal artery. Next, retinas were subjected to 90 minutes of ischemia followed
      by 24 hours of reperfusion. After this procedure, heme oxygenase-1 (HO-1)-related
      protein expression and enzyme activity, HO-1-related endogenous CO production,
      and ionic imbalance including tissue Na(+), K(+), and Ca(2+) in untreated and
      treated ischemic/reperfused retinas were measured. RESULTS: Retinal
      ischemia/reperfusion resulted in a significant reduction (to 10%) in HO-1 protein
      expression, enzyme activity, and HO-1-related endogenous CO production in the
      retina. These changes were accompanied by increases in retinal Na(+) and Ca(2+)
      gains and loss of K(+). In rats treated with 10 and 30 mg/kg of sour cherry
      flavonoid-rich extract, after 24 hours of reperfusion, tissue Na(+) and Ca(2+)
      accumulation and K(+) loss were prevented in comparison with the drug-free
      control. CONCLUSIONS: Sour cherry seed flavonoid-rich extract showed a protective
      effect against reperfusion-induced injury through its ability to reduce the
      changes in concentrations of retinal ions through HO-1-related endogenous CO
      production in the ischemic/reperfused retina.

PMID- 15452084
TI  - A model of best vitelliform macular dystrophy in rats.
AB  - PURPOSE: The VMD2 gene, mutated in Best macular dystrophy (BMD) encodes
      bestrophin, a 68-kDa basolateral plasma membrane protein expressed in retinal
      pigment epithelial (RPE) cells. BMD is characterized by a depressed light peak
      (LP) in the electro-oculogram. Bestrophin is thought to be the Cl channel that
      generates the LP. The goal was to generate an animal model of BMD and to
      determine the effects of bestrophin overexpression on the RPE-generated
      components of the ERG. METHODS: Bestrophin or bestrophin mutants (W93C or R218C)
      were overexpressed in the RPE of rats by injection of replication-defective
      adenovirus. Immunofluorescence microscopy and ERG recordings were used to study
      subsequent effects. RESULTS: Bestrophin was confined to the basolateral plasma
      membrane of the RPE. Neither wild-type (wt) nor mutant bestrophin affected the a-
      or b-waves of the ERG. Wt bestrophin, however, increased the c-wave and fast
      oscillation (FO), but not the LP. In contrast, both mutants had little or no
      effect on the c-wave and FO, but did reduce LP amplitude. LP amplitudes across a
      range of stimuli were not altered by wt bestrophin, though the luminance response
      function was desensitized. LP response functions were unaffected by bestrophin
      R218C but were significantly altered by bestrophin W93C. CONCLUSIONS: A model of
      BMD was developed in the present study. Because overexpression of wt bestrophin
      shifted luminance response but did not alter the range of LP response amplitudes,
      the authors conclude that the rate-limiting step for generating LP amplitude
      occurs before activation of bestrophin or that bestrophin does not directly
      generate the LP conductance.

PMID- 15452085
TI  - Adenosine A1-receptor modulation of glutamate-induced calcium influx in rat
      retinal ganglion cells.
AB  - PURPOSE: Although adenosine receptors (A(1)-Rs and A(2)-Rs) have been identified
      in the mammalian retina, the role of adenosine in this tissue is not fully
      understood. The purpose of this work was to investigate the action of adenosine
      on glutamate-induced calcium influx in rat retinal ganglion cells (RGCs) and to
      determine whether adenosine modulates RGC voltage-gated calcium channels.
      METHODS: Purified RGC cultures were generated from neonatal rats with a two-step
      panning procedure. Isolated RGCs were loaded with the ratiometric calcium
      indicator dye fura-2, and the effect of adenosine (and related agonists and
      antagonists) on intracellular calcium levels ([Ca(2+)](i)) during exposure to
      glutamate (10 microM with 10 microM glycine) was assessed. The effect of
      adenosine on calcium channel currents was also studied in isolated RGCs with
      whole-cell patch-clamp techniques. In addition, the effect of adenosine on
      [Ca(2+)](i) was investigated in fura dextran-loaded RGCs in an intact adult rat
      retina preparation. RESULTS: In isolated RGCs, adenosine (10 and 100 microM)
      significantly reduced the glutamate-induced increase in [Ca(2+)](i) (
      approximately 30%). The effect of adenosine was blocked by the A(1)-R antagonist
      8-cyclopentyl-1,3-dipropylxanthine (DPCPX), but not by the A(2)-R antagonist 3,7
      dimethyl-1-propargylxanthine (DMPX). Adenosine (10 microM) inhibited calcium
      channel currents by 43%, and again this effect was blocked by DPCPX, but not
      DMPX. Adenosine (100 microM) also significantly reduced the elevation of
      [Ca(2+)](i) in RGCs in the intact retina during exposure to N-methyl-d-aspartate
      (NMDA; 100 microM). CONCLUSIONS: Adenosine can inhibit glutamate-induced calcium
      influx and voltage-gated calcium currents in rat RGCs through A(1)-R activation.
      This work supports a role for adenosine as a neuromodulator of mammalian RGCs.

PMID- 15452086
TI  - Displaced amacrine cells disappear from the ganglion cell layer in the central
      retina of adult fish during growth.
AB  - PURPOSE: Fish grow throughout life, including enlargement of eye and retina.
      Retinal growth involves several mechanisms of adjustment, such as cell addition
      and dendritic growth. To discover possible other means with which the animals
      adjust to changing eye size, the distribution of displaced amacrine cells (DACs)
      and ganglion cells (GCs) was analyzed in the retina of three sizes of a South
      American cichlid, the blue arcara Aequidens pulcher. METHODS: DACs were
      identified by staining with antibodies specific for the calcium-binding protein
      parvalbumin. They were also weakly positive for staining against choline acetyl
      transferase (ChaT). GCs were labeled retrogradely with rhodamine dextran.
      Densities for both DACs and GCs were lower in the retinas of large fish. To
      distinguish changes due to eye size from specific adjustments, the proportions of
      DACs to GCs were examined, rather than the absolute cell densities, in various
      retinal regions in cryostat sections and wholemount preparations from fish of the
      three sizes. RESULTS: The analyses suggest that, in small and large fish, DACs
      and GCs were produced in similar proportions (ratio of DACs to GCs, approximately
      0.62) in the retinal periphery where new retinal tissue was added by the germinal
      zone. However, in the central retina of large fish, this proportion was shifted
      toward GCs (DAC-GC ratio as low as 0.25). CONCLUSIONS: During growth of the eye,
      the proportion of DACs in the ganglion cell layer decreases, indicating that
      these cells are eliminated from the ganglion cell layer by some unknown
      mechanism.

PMID- 15452087
TI  - CAI is a potent inhibitor of neovascularization and imparts neuroprotection in a
      mouse model of ischemic retinopathy.
AB  - PURPOSE: This study was performed to characterize the effects of an
      antimetastatic and antiangiogenic molecule, carboxyamido-triazole (CAI), on
      retinal neovascularization in a mouse model. METHODS: Neonatal mice were
      subjected to 75% to 85% oxygen from postnatal day (PND)-7 to -12 and then were
      abruptly placed in room air. CAI (100 mg/kg) or vehicle control polyethylene
      glycol-400 (PEG-400) was given daily from PND-14 to -16, and mice were killed on
      PND-17 to form group A. In group B, CAI (100 mg/kg) or PEG-400 was given daily
      from PND-17 to -19, and mice were killed on PND-20. RESULTS: A 92% inhibition of
      neovascular cell nuclei on light microscopy was observed in mice treated with CAI
      in group A (P < 0.0001). Fluorescein-perfusion demonstrated a similar profound
      inhibition of neovascular frond formation in CAI-treated mice in group A. In
      group B, after neovascular fronds had already formed, CAI administration reduced
      neovascular cell nuclei by 72% (P < 0.001). Fluorescein perfusion studies
      confirmed that CAI induced regression of neovascular fronds. Similar amounts of
      posterior retinal ischemia were observed in all mice at both PND-17 and -20. In
      group A and B animals, CAI increased immunoreactivity of a cellular survival
      factor, Bcl-2, decreased TUNEL-positive cells, and after CAI treatment the normal
      morphology of the inner retina remained intact. CONCLUSIONS: CAI almost
      completely abolished retinal neovascularization in group A, and neovascular
      fronds involuted after treatment with CAI in group B. Thus, CAI is a potent
      inhibitor of ischemia-induced neovascularization and also imparts retinal
      neuroprotection after ischemic injury.

PMID- 15452088
TI  - Survival of retinal pigment epithelium after exposure to prolonged oxidative
      injury: a detailed gene expression and cellular analysis.
AB  - PURPOSE: To detail, by DNA microarrays and cellular structure labeling, the in
      vitro responses of retinal pigment epithelial (RPE) cells to a nonlethal dose of
      the oxidant agent hydroquinone (HQ). METHODS: The viability of growth-quiescent
      ARPE-19 cells after treatment with HQ was measured by XTT conversion, (3)H
      leucine incorporation, trypan blue exclusion, and the presence of DNA laddering.
      The effect of a nonlethal dose of HQ on the localization of apoptosis-induced
      factor (AIF) and phosphorylation of stress-activated kinase-2/p38 (SAPK2/p38) was
      detected by immunocytochemistry. Actin structures were visualized by phalloidin
      staining. Cell membrane blebbing was detected using GFP-membrane-labeled RPE
      cells (ARPE-GFP-c'-rRas). Changes in gene expression patterns of RPE cells within
      48 hours of prolonged treatment with a nonlethal dose of HQ were evaluated by
      microarray analysis and confirmed by Northern blotting. RESULTS: The viability of
      RPE after a prolonged sublethal injury dose of HQ was determined by multiple
      assays and confirmed by the absence of AIF translocation or DNA laddering.
      Prolonged exposure (16 hours) of RPE cells to a nonlethal dose of HQ resulted in
      actin rearrangement into globular aggregates and cell membrane blebbing. Kinetic
      microarray analysis at several time points over a 48-hour recovery period
      revealed significant upregulation of genes involved in ameliorating the oxidative
      stress, chaperone proteins, anti-apoptotic factors, and DNA repair factors, and
      downregulation of pro-apoptotic genes. Genes involved in extracellular matrix
      functions were also dysregulated. Recovery of RPE cells after the injury was
      confirmed by the normalization of gene expression dysregulation back to baseline
      levels within 48 hours. CONCLUSIONS: RPE cells avoided cell death and recovered
      from prolonged oxidative injury by activating a host of defense mechanisms while
      simultaneously triggering genes and cellular responses that may be involved in
      RPE disease development.

PMID- 15452089
TI  - Molecular and cellular reactions of retinal ganglion cells and retinal glial
      cells under centrifugal force loading.
AB  - PURPOSE: To investigate changes in retinal ganglion cell (RGC) survival and
      morphology, retinal glial cell effects on RGC survival, and changes in mRNA
      expression during centrifugal force loading using a newly developed device.
      METHODS: Changes in RGC survival and morphology were examined when isolated RGCs
      from 2-day-old rats were loaded with centrifugal force equivalent to 16, 28, or
      33 mm Hg. The effects of cocultured retinal glial cells on RGC survival were
      studied in the presence of centrifugal force equivalent to 16 and 28 mm Hg for 48
      hours. The microarray method and real-time polymerase chain reaction confirmed
      changes in mRNA expression when RGCs and retinal glial cells were loaded with
      centrifugal force equivalent to 28 mm Hg for 24 hours. RESULTS: The survival of
      isolated RGCs and the number of neurites were significantly decreased by
      centrifugal force loading. Conversely, there was no significant change in the
      survival of isolated retinal glial cells. The survival of cocultured RGCs was
      significantly better than that of isolated RGCs. In contrast to the numerous
      changes in the mRNA expression of retinal glial cells subjected to centrifugal
      force loading, there was no significant change in the mRNA expression of RGCs.
      CONCLUSIONS: The developed device may have potential for use as an in vitro model
      of RGC damage. The response to centrifugal force loading varies according to cell
      type, and the marked changes in the mRNA expression of retinal glial cells may be
      involved in the improvement of RGC survival.

PMID- 15452090
TI  - Metipranolol blunts nitric oxide-induced lipid peroxidation and death of retinal
      photoreceptors: a comparison with other anti-glaucoma drugs.
AB  - PURPOSE: To determine the effect of the nitric oxide donor sodium nitroprusside
      (SNP) on rat retinas and to see whether detrimental changes could be attenuated
      by known antiglaucoma drugs. METHODS: SNP was injected into the rat eye and
      retinas were analyzed by the terminal-deoxynucleotidyl transferase dUTP-linked
      nick end labeling (TUNEL) procedure and by immunohistochemistry. In some
      instances, retinal homogenates were analyzed by immunoblot for proteins
      associated with either photoreceptors or with cell death. Analysis of lipid
      peroxidation in retinal homogenates was by the thiobarbituric acid reactive
      species (TBARS) formation METHOD:  RESULTS: SNP caused an increase in the number
      of retinal photoreceptors labeled for DNA breakdown by the TUNEL procedure and
      for caspase-3 and Bcl-2. After intravitreal injection of SNP, breakdown of
      poly(ADP-ribose) polymerase and an increase in the level of active forms of
      caspase-3 and Bcl-2 were detected. Furthermore, photoreceptor-specific rhodopsin
      kinase was reduced. SNP also stimulated formation of TBARS in retinal
      homogenates, occurring to a greater extent in retinas from young Royal College of
      Surgeons rats lacking photoreceptor degeneration. This supports the view that the
      photoreceptors are the prime target for SNP. Significantly, of several
      antiglaucoma drugs tested only metipranolol and its active metabolite,
      desacetylmetipranolol, blunted the SNP-induced retinal changes. CONCLUSIONS: Of
      all antiglaucoma drugs tested, only metipranolol was able to attenuate SNP
      induced lipid peroxidation and activation of apoptosis in photoreceptors. Because
      oxidative injury has been implicated in the pathogenesis of certain ocular
      diseases, these findings could prove to be of clinical significance.

PMID- 15452091
TI  - Inhibition of oxygen-induced retinopathy in RTP801-deficient mice.
AB  - PURPOSE: Ischemic proliferative retinopathy, which occurs as a complication of
      diabetes mellitus, prematurity, or retinal vein occlusion, is a major cause of
      blindness worldwide. In addition to retinal neovascularization, it involves
      retinal degeneration, of which apoptosis is the main cause. A prior report has
      described the cloning of a novel HIF-1-responsive gene, RTP801, which displays
      strong hypoxia-dependent upregulation in ischemic cells of neuronal origin, both
      in vitro and in vivo. Moreover, inducible overexpression of RTP801 promotes the
      apoptotic death of differentiated neuron-like PC12 cells and increases their
      sensitivity to ischemic injury and oxidative stress. The purpose of the study was
      to examine the potential role of RTP801 in the pathogenesis of retinopathy, using
      RTP801-deficient mice. METHODS: Wild-type and RTP801-knockout mice were used in a
      model of retinopathy of prematurity (ROP). Their retinas were collected at
      postnatal day (P)14 and P17. They were examined by fluorescein angiography and by
      analysis of VEGF expression, neovascularization, and apoptosis. RESULTS: The
      expression of RTP801 was induced in the wild-type retina after hypoxia treatment.
      The retinal expression of VEGF after transfer to normoxic conditions was
      similarly upregulated in both wild-type and knockout mice. Nevertheless, the
      retinas of the RTP801-knockout mice in an ROP model showed a significant
      reduction in retinal neovascularization (P < 0.0001) and in the number of
      apoptotic cells in the inner nuclear layer (P < 0.0001). CONCLUSIONS: In the
      absence of RTP801 expression, development of retinopathy in the mouse model of
      ROP was significantly attenuated, thus implying an important role of RTP801 in
      the pathogenesis of ROP.

PMID- 15452092
TI  - Effects of photorefractive keratectomy-induced defocus on emmetropization of
      infant rhesus monkeys.
AB  - PURPOSE: To investigate whether photorefractive keratectomy (PRK) performed in
      infant primates can modify emmetropization and therefore could be used to study
      mechanisms of refractive error development. METHODS: Six healthy rhesus monkeys
      ranging in age from 2 to 3 months were randomly divided into two groups (n = 3
      each). Anisometropia was induced in each animal by performing PRK on one eye.
      Hyperopic anisometropia was induced in group A monkeys by flattening the cornea
      of the right eye, whereas myopic anisometropia was produced in group B monkeys by
      steepening the cornea of the right eye. Corneal morphology and topography,
      refractive status, and axial growth were evaluated over a 5-month observation
      period. RESULTS: All the PRK-treated corneas were re-epithelialized and
      transparent within 3 days after surgery. Subsequently, all the surgically treated
      eyes exhibited interocular alterations in axial growth rate that were appropriate
      to compensate for the PRK-induced anisometropia. Specifically, vitreous chamber
      elongation rates were faster in the eyes with induced hyperopias than in their
      fellow eyes (0.63 +/- 0.05 mm vs. 0.40 +/- 0.09 mm), but slower in the eyes with
      induced myopia than in their fellow eyes (0.58 +/- 0.13 mm vs. 0.73 +/-0.10 mm).
      In some animals, the recovery from the induced anisometropia was facilitated by
      interocular differences in the rate of corneal flattening. However, the rates of
      corneal flattening in the treated eyes and their fellow eyes were not
      significantly different. CONCLUSIONS: PRK-induced defocus predictably alters
      axial growth rate and the normal course of emmetropization in developing eyes.
      Thus, PRK is a useful alternative to current methods used to impose experimental
      refractive errors in laboratory animals. These results also indicate that
      refractive surgery performed in childhood may affect normal growth of the eye,
      resulting in decreased predictability of future refractive status.

PMID- 15452093
TI  - Effect of short-term hyperglycemia on multifocal electroretinogram in diabetic
      patients without retinopathy.
AB  - PURPOSE: To investigate the effect of variations in blood glucose level on the
      multifocal electroretinogram (mfERG) in patients with type 1 diabetes without
      retinopathy. METHODS: Fourteen patients were clamped sequentially and in random
      order at 5 and 15 mM blood glucose for 75 minutes on the same day. MfERG was
      recorded in one eye at each level of blood glucose level. RESULTS: Compared to
      euglycemia (5 mM), hyperglycemia was associated with an overall decrease in the
      implicit times and an increase in the amplitudes of the multifocal ERG. The
      effect of hyperglycemia on implicit time reached statistical significance for the
      summed first positive (P1) and second negative component (N2) of the first-order
      kernel (P = 0.0020 and 0.0005, respectively) and all components of the second
      order kernel (P = 0.014, 0.0037, and 0034, respectively). These changes in the
      mfERG demonstrated no significant variation in relation to retinal location or
      long-term blood glucose level. CONCLUSIONS: Steady-state hyperglycemia induced
      shorter first- and second-order kernel implicit times in patients with type 1
      diabetes without retinopathy. The effects of hyperglycemia were not significant
      with retinal location. These results support the hypothesis that hyperglycemia
      accelerates retinal metabolism.

PMID- 15452094
TI  - Mapping cone- and rod-induced retinal responsiveness in macaque retina by optical
      imaging.
AB  - PURPOSE: To map the distribution of cone- or rod-induced retinal responsiveness
      by optical imaging from macaque retina. METHODS: The light reflectance changes in
      the posterior retina after a flash stimulus in anesthetized rhesus monkeys were
      measured by a modified fundus camera system equipped with a charge-coupled device
      (CCD) camera. The response topography of the optical signals was obtained in
      either light- or dark-adapted conditions. RESULTS: With infrared observation
      light, the whole posterior pole became darkened after the stimulus. The response
      topography in light-adapted conditions demonstrated a steep peak of darkening at
      the fovea, together with the gradual decrease of signal intensity away from the
      fovea toward the periphery. In dark-adapted conditions, the optical signal showed
      additional peaks along the circular region surrounding the macula at the
      eccentricity of the optic disc, together with the central peak at the fovea. A
      statistically significant positive correlation was obtained between the light
      reflectance changes in infrared observation light and the focal responses in
      multifocal electroretinogram (mfERG) at the corresponding retinal locations.
      CONCLUSIONS: The response topography in the retina, obtained by optical imaging,
      was consistent with psychophysical cone or rod sensitivity in humans and anatomic
      cone or rod distribution in humans and macaques. The cone- or rod-induced retinal
      responsiveness within the posterior pole region was noninvasively recorded within
      a short recording time.

PMID- 15452095
TI  - Photopic ERGs in patients with optic neuropathies: comparison with primate ERGs
      after pharmacologic blockade of inner retina.
AB  - PURPOSE: To determine whether anterior ischemic optic neuropathy and compressive
      optic neuropathy in humans alter the photopic flash ERG and to investigate the
      cellular origins of the waves that are affected by pharmacologic agents in
      primates. METHODS: Photopic flash ERGs were recorded differentially, with DTL
      electrodes, between the two eyes of 22 patients with diagnosed optic neuropathy
      (n = 17, anterior ischemic optic neuropathy [AION]; n = 5, compressive optic
      neuropathy) and 25 age-matched control subjects and in 17 eyes of 13 monkeys
      (Macaca mulatta). The stimulus consisted of brief (<5 ms) red (lambda(max) = 660
      nm) Ganzfeld flashes (energy range, 0.5-2.0 log td-s) delivered on a rod
      saturating blue background of 3.7 log sc td (lambda(max) = 460 nm). An eye of the
      patient with ischemic changes at the disc was classified as symptomatic if it
      showed visual field defects with a mean deviation (MD) of P < 2%. Recordings in
      macaque monkeys were made before and after inner retinal blockade with
      tetrodotoxin (TTX) (1.2-2.1 microM; n = 7), TTX+N-methyl-d-aspartate (NMDA; 1.4
      6.4 mM; n = 7), and cis-2, 3 piperidine dicarboxylic acid (PDA; 3.3-3.8 mM; n =
      3). RESULTS: The PhNR amplitude was significantly reduced in both symptomatic (P
      = 3.4 x 10(-8)) and asymptomatic (P = 0.036) eyes of patients with AION or
      compressive optic neuropathy (P = 0.0054) compared with control subjects. The
      PhNR amplitude in the symptomatic eye showed a moderate correlation with field
      defects (P < 0.05) similar to previous findings in open-angle glaucoma. The a
      wave also was reduced significantly in the symptomatic eye (P = 0.0002) of
      patients with AION. The i-wave, a positive wave on the trailing edge of the b
      wave peaking around 50 ms, became more prominent in eyes in which the PhNR was
      significantly reduced. In monkeys, the PhNR was eliminated by TTX. The a-wave at
      the peak and later times was reduced by TTX, further reduced by NMDA, and
      eliminated after PDA in response to the red stimuli. PDA also eliminated the i
      wave. CONCLUSIONS: PhNR amplitude is significantly reduced in eyes with open
      angle glaucoma, AION, and compressive optic neuropathy. Experiments in primates
      indicate that this reduction reflects loss of a spike-driven contribution to the
      photopic ERG. There also are small spike-driven contributions to the a-wave
      elicited by full-field red stimuli. The i-wave, which becomes more prominent when
      the PhNR is reduced, has origins in the off-pathway distal to the ganglion cells.

PMID- 15452097
TI  - The hospitalist: a patient-focused paradigm?

PMID- 15452096
TI  - Spatial properties of photophobia.
AB  - PURPOSE: To determine the spatial properties of stimuli that elicit photophobia
      (PP) in normal subjects: Does PP exhibit spatial summation? Are different
      parafoveal quadrants (superior, inferior, temporal, and nasal) of the retina
      differentially sensitive in PP? What is the relationship between PP sensitivity
      and retinal eccentricity? What is the relationship between the spatial properties
      of PP and the spatial distribution of macular pigment (MP)? METHODS: A Maxwellian
      view optical system with a xenon light source was used to present the stimuli.
      Four normal subjects viewed stimuli of various sizes, retinal locations, and one
      of two chromatic contents: xenon-white and a broadband orange. The intensity of
      the test stimulus was increased between trials until the PP threshold was
      reached. The squinting response corresponding to PP was assessed by
      electromyography and used as an objective criterion of PP. Three parameters were
      examined: stimulus size, parafoveal retinal locus (superior, inferior, temporal,
      and nasal), and retinal eccentricity (extending into the perifovea). Spatial
      profiles of MP were measured psychophysically using heterochromatic flicker
      photometry (HFP). RESULTS: Spatial summation for PP was found essentially to
      adhere to Piper's law (radiance proportional to square root of stimulus area).
      The PP response was greater to centrally than peripherally viewed targets. In
      this regard, MP acted as a spatially integrated filter in the attenuation of PP.
      CONCLUSIONS: The degree of spatial summation found for PP indicates that an
      increase of 1.0 log unit in field area results in an approximately 0.57-log-unit
      decrease in the radiance required to elicit PP. PP appears to serve the function
      of retinal photoprotection.

PMID- 15452098
TI  - Bridging perspectives, but regretting demise of internship.

PMID- 15452099
TI  - Should DOs be more birdbrained?

PMID- 15452100
TI  - DO notes difference between residency programs.

PMID- 15452101
TI  - Influenza epidemic or pandemic? Time to roll up sleeves, vaccinate patients, and
      hone osteopathic manipulative skills.

PMID- 15452102
TI  - Home treadmill injuries in infants and children aged to 5 years: a review of
      Consumer Product Safety Commission data and an illustrative report of case.
AB  - Approximately 8700 injuries from home exercise equipment occur annually in
      children in the United States. Home treadmills, which have been growing steadily
      in popularity during the past decade, pose a specific hazard to infants and
      children aged 5 years or younger, a population at increased risk of injury to the
      upper extremities (ie, arm, forearm, wrist, hand, and fingers). The authors also
      provide an illustrative report of case of a 2-year-old boy whose hand injury
      resulted from a home treadmill. Analysis and frequency reporting of United States
      Consumer Product Safety Commission data for home treadmill injuries in this
      demographic group are presented. From January 1, 1996, to September 30, 2000, the
      number of home treadmill injuries reported to the National Electronic Injury
      Surveillance System was 1009. Three hundred of these (29.7%) were in infants and
      children aged to 5 years. Abrasions or contusions (or both) of the upper
      extremities were the most common injury. Although the number of home treadmill
      injuries to children being reported is low, the potential for costly and serious
      complications has been demonstrated previously. The authors conclude that
      additional home treadmill safety measures and guidelines must be established.

PMID- 15452103
TI  - Myasthenia gravis.
AB  - Myasthenia gravis (MG) is a chronic neuromuscular disorder that can lead to
      various degrees of neurologic dysfunction. Initial patient presentation may be a
      diagnostic dilemma to the family physician unfamiliar with testing methods for
      and the treatment and care of patients with MG. The author focuses on the
      clinical features, electrodiagnostic testing, and treatment of patients with MG.

PMID- 15452105
TI  - Muscarinic toxin 7 selectivity is dictated by extracellular receptor loops.
AB  - Muscarinic toxin 7 (MT7) is a mamba venom protein antagonist with extremely high
      selectivity for the M1 muscarinic acetylcholine receptor. To map the sites for
      the interaction of MT7 with muscarinic receptors we have used chimeric M1:M3
      receptors and site-directed mutagenesis of the M3 and M4 receptor subtypes. Two
      Glu residues in M1, one in extracellular loop 2 and one in extracellular loop 3,
      were found to be important for the high affinity binding of MT7. Substitution of
      the corresponding Lys residues in the M3 receptor with Glu converted the M3
      mutant to an MT7 binding receptor, albeit with lower affinity compared with M1. A
      Phe --> Tyr substitution in extracellular loop 2 of M3 together with the 2 Glu
      mutations generated a receptor with an increased MT7 affinity (apparent Ki = 0.26
      nM in a functional assay) compared with the M1 receptor (apparent Ki = 1.31 nM).
      The importance of the identified amino acid residues was confirmed with a mutated
      M4 receptor constructs. The results indicate that the high selectivity of MT7 for
      the M1 receptor depends on very few residues, thus providing good prospects for
      future design and synthesis of muscarinic receptor-selective ligands.

PMID- 15452106
TI  - Noninvasive imaging of 5-HT3 receptor trafficking in live cells: from
      biosynthesis to endocytosis.
AB  - Sequential stages in the life cycle of the ionotropic 5-HT(3) receptor (5-HT(3)R)
      were resolved temporally and spatially in live cells by multicolor fluorescence
      confocal microscopy. The insertion of the enhanced cyan fluorescent protein into
      the large intracellular loop delivered a fluorescent 5-HT(3)R fully functional in
      terms of ligand binding specificity and channel activity, which allowed for the
      first time a complete real-time visualization and documentation of intracellular
      biogenesis, membrane targeting, and ligand-mediated internalization of a receptor
      belonging to the ligand-gated ion channel superfamily. Fluorescence signals of
      newly expressed receptors were detectable in the endoplasmic reticulum about 3 h
      after transfection onset. At this stage receptor subunits assembled to form
      active ligand binding sites as demonstrated in situ by binding of a fluorescent 5
      HT(3)R-specific antagonist. After novel protein synthesis was chemically blocked,
      the 5-HT(3) R populations in the endoplasmic reticulum and Golgi cisternae moved
      virtually quantitatively to the cell surface, indicating efficient receptor
      folding and assembly. Intracellular 5-HT(3) receptors were trafficking in vesicle
      like structures along microtubules to the cell surface at a velocity generally
      below 1 mum/s and were inserted into the plasma membrane in a characteristic
      cluster distribution overlapping with actin-rich domains. Internalization of cell
      surface 5-HT(3) receptors was observed within minutes after exposure to an
      extracellular agonist. Our orchestrated use of spectrally distinguishable
      fluorescent labels for the receptor, its cognate ligand, and specific organelle
      markers can be regarded as a general approach allowing subcellular insights into
      dynamic processes of membrane receptor trafficking.

PMID- 15452107
TI  - Analysis of the third transmembrane domain of the human type 1 angiotensin II
      receptor by cysteine scanning mutagenesis.
AB  - Activation of G protein-coupled receptors by agonists involves significant
      movement of transmembrane domains (TMD) following agonist binding. The underlying
      structural mechanism by which receptor activation takes place is largely unknown
      but can be inferred by detecting variability within the environment of the ligand
      binding pocket, which is a water-accessible crevice surrounded by the seven TMD
      helices. Using the substituted-cysteine accessibility method, we identified the
      residues within the third TMD of the wild-type angiotensin II (AT1) receptor that
      contribute to the formation of the binding site pocket. Each residue within the
      Ile103-Tyr127 region was mutated one at a time to a cysteine. Treating the A104C,
      N111C, and L112C mutant receptors with the charged sulfhydryl-specific alkylating
      agent methanethiosulfonate-ethylammonium (MTSEA) strongly inhibited ligand
      binding, which suggests that these residues orient themselves within the water
      accessible binding pocket of the AT1 receptor. Interestingly, this pattern of
      acquired MTSEA sensitivity was altered for TMD3 reporter cysteines engineered in
      a constitutively active AT1 receptor. Indeed, two additional mutants (S109C and
      V116C) were found to be sensitive to MTSEA treatment. Our results suggest that
      constitutive activation of the AT1 receptor causes a minor counterclockwise
      rotation of TMD3, thereby exposing residues, which are not present in the
      inactive state, to the binding pocket. This pattern of accessibility of residues
      in the TMD3 of the AT1 receptor parallels that of homologous residues in
      rhodopsin. This study identified key elements of TMD3 that contribute to the
      activation of class A G protein-coupled receptors through structural
      rearrangements.

PMID- 15452108
TI  - Acute pH-dependent regulation of AE2-mediated anion exchange involves discrete
      local surfaces of the NH2-terminal cytoplasmic domain.
AB  - We have previously defined in the NH2-terminal cytoplasmic domain of the mouse
      AE2/SLC4A2 anion exchanger a critical role for the highly conserved amino acids
      (aa) 336-347 in determining wild-type pH sensitivity of anion transport. We have
      now engineered hexa-Ala ((A)6) and individual amino acid substitutions to
      investigate the importance to pH-dependent regulation of AE2 activity of the
      larger surrounding region of aa 312-578. 4,4'-Diisothiocyanostilbene-2,2'
      disulfonic acid (DIDS)-sensitive 36Cl- efflux from AE2-expressing Xenopus oocytes
      was monitored during changes in pHi or pHo in HEPES-buffered and in 5% CO2/HCO3- 
      buffered conditions. Wild-type AE2-mediated 36Cl- efflux was profoundly inhibited
      at low pHo, with a pHo(50) value = 6.75 +/- 0.05 and was stimulated up to 10-fold
      by intracellular alkalinization. Individual mutation of several amino acid
      residues at non-contiguous sites preceding or following the conserved sequence aa
      336-347 attenuated pHi and/or pHo sensitivity of 36Cl- efflux. The largest
      attenuation of pH sensitivity occurred with the AE2 mutant (A)6357-362. This
      effect was phenocopied by AE2 H360E, suggesting a crucial role for His360.
      Homology modeling of the three-dimensional structure of the AE2 NH2-terminal
      cytoplasmic domain (based on the structure of the corresponding region of human
      AE1) predicts that those residues shown by mutagenesis to be functionally
      important define at least one localized surface region necessary for regulation
      of AE2 activity by pH.

PMID- 15452109
TI  - Human alpha-1-microglobulin is covalently bound to kynurenine-derived
      chromophores.
AB  - Alpha-1-microglobulin carries a set of covalently linked chromophores that give
      it a peculiar yellow-brown color, fluorescence properties, and both charge and
      size heterogeneity. In this report it is shown that these features are due to the
      adducts with the tryptophan metabolite, 3-hydroxykynurenine, and its autoxidation
      products and that the modification is more pronounced in the protein isolated
      from urine of hemodialyzed patients. The light yellow amniotic fluid alpha-1
      microglobulin acquires the optical properties and charge heterogeneity of the
      urinary counterpart following incubation with kynurenines. The colored amino acid
      adducts of urinary and amniotic fluid alpha-1-microglobulins were separated by
      chromatography after acid hydrolysis and analyzed by mass spectrometry. Human
      serum albumin samples, native and treated with 3-hydroxykynurenine in the
      presence of oxygen, were used as a control. The retention times and mass
      fragmentation products were compared, and a lysyl adduct with hydroxantommathin
      was identified in the urinary alpha-1-microglobulin and in the modified albumin
      samples. The more extensive modification of the urinary protein appears to be
      correlated with uremia, a condition in which the catabolism of tryptophan via the
      kynurenine pathway is increased, and the consequent rise in the concentration of
      its derivatives is accompanied by the oxidative processes due to the hemodialysis
      treatment. The oxidative derivatives of 3-hydroxykynurenine, which are known to
      act as protein cross-linking agents, are the likely cause of the propensity of
      urinary alpha-1-microglobulin to form dimers and oligomers. This process, as well
      as the redox properties of these metabolites, may contribute to the toxic effects
      of the kynurenine species.

PMID- 15452110
TI  - Mannose 6-phosphorylated proteins are required for tumor necrosis factor-induced
      apoptosis: defective response in I-cell disease fibroblasts.
AB  - Whereas caspases are essential components in apoptosis, other proteases seem to
      be involved in programmed cell death. This study investigated the role of
      lysosomal mannose 6-phosphorylated proteins in tumor necrosis factor (TNF)
      induced apoptosis. We report that fibroblasts isolated from patients affected
      with inclusion-cell disease (ICD), having a deficient activity of almost all
      lysosomal hydrolases, are resistant to the toxic effect of TNF. These mutant
      cells exhibited a defect in TNF-induced caspase activation, Bid cleavage, and
      release of cytochrome c. In contrast, TNF-induced p42/p44 MAPK activation and
      CD54 expression remained unaltered. Human ICD lymphoblasts and fibroblasts
      derived from mice nullizygous for Igf2 and the two mannose 6-phosphate (M6P)
      receptors, Mpr300 and Mpr46, which develop an ICD-like phenotype, were also
      resistant to CD95 ligand and TNF, respectively. Moreover, correction of the
      lysosomal enzyme defect of ICD fibroblasts, using a medium enriched in M6P
      containing proteins, enabled restoration of sensitivity to TNF. This effect was
      blocked by exogenous M6P but not by cathepsin B or L inhibitors. Altogether,
      these findings suggest that some M6P-bearing glycoproteins modulate the
      susceptibility to TNF-induced apoptosis. As a matter of fact, exogenous
      tripeptidyl peptidase 1, a lysosomal carboxypeptidase, could sensitize ICD
      fibroblasts to TNF. These observations highlight the hitherto unrecognized role
      of some mannose 6-phosphorylated proteins such as tripeptidyl peptidase 1 in the
      apoptotic cascade triggered by TNF.

PMID- 15452111
TI  - The microglia-activating potential of thrombin: the protease is not involved in
      the induction of proinflammatory cytokines and chemokines.
AB  - The serine protease thrombin is known as a blood coagulation factor. Through
      limited cleavage of proteinase-activated receptors it can also control growth and
      functions in various cell types, including neurons, astrocytes, and microglia
      (brain macrophages). A number of previous studies indicated that thrombin induces
      the release of proinflammatory cytokines and chemokines from microglial cells,
      suggesting another important role for the protease beyond hemostasis. In the
      present report, we provide evidence that this effect is not mediated by any
      proteolytic or non-proteolytic mechanism involving thrombin proper. Inhibition of
      the enzymatic thrombin activity did not affect the microglial release response.
      Instead the cyto-/chemokine-inducing activity solely resided in a high molecular
      weight protein fraction that could be isolated in trace amounts even from
      apparently homogenous alpha- and gamma-thrombin preparations. High molecular
      weight material contained thrombin-derived peptides as revealed by mass
      spectrometry but was devoid of thrombin-like enzymatic activity. Separated from
      the high molecular weight fraction by fast protein liquid chromatography,
      enzymatically intact alpha- and gamma-thrombin failed to trigger any release. Our
      findings may force a revision of the notion that thrombin itself is a direct
      proinflammatory release signal for microglia. In addition, they could be relevant
      for the study of other cellular activities and their assignment to this protease.

PMID- 15452112
TI  - The methylerythritol phosphate pathway is functionally active in all
      intraerythrocytic stages of Plasmodium falciparum.
AB  - Two genes encoding the enzymes 1-deoxy-D-xylulose-5-phosphate synthase and 1
      deoxy-D-xylulose-5-phosphate reductoisomerase have been recently identified,
      suggesting that isoprenoid biosynthesis in Plasmodium falciparum depends on the
      methylerythritol phosphate (MEP) pathway, and that fosmidomycin could inhibit the
      activity of 1-deoxy-D-xylulose-5-phosphate reductoisomerase. The metabolite 1
      deoxy-D-xylulose-5-phosphate is not only an intermediate of the MEP pathway for
      the biosynthesis of isopentenyl diphosphate but is also involved in the
      biosynthesis of thiamin (vitamin B1) and pyridoxal (vitamin B6) in plants and
      many microorganisms. Herein we report the first isolation and characterization of
      most downstream intermediates of the MEP pathway in the three intraerythrocytic
      stages of P. falciparum. These include, 1-deoxy-D-xylulose-5-phosphate, 2-C
      methyl-D-erythritol-4-phosphate, 4-(cytidine-5-diphospho)-2-C-methyl-D
      erythritol, 4-(cytidine-5-diphospho)-2-C-methyl-D-erythritol-2-phosphate, and 2-C
      methyl-D-erythritol-2,4-cyclodiphosphate. These intermediates were purified by
      HPLC and structurally characterized via biochemical and electrospray mass
      spectrometric analyses. We have also investigated the effect of fosmidomycin on
      the biosynthesis of each intermediate of this pathway and isoprenoid biosynthesis
      (dolichols and ubiquinones). For the first time, therefore, it is demonstrated
      that the MEP pathway is functionally active in all intraerythrocytic forms of P.
      falciparum, and de novo biosynthesis of pyridoxal in a protozoan is reported. Its
      absence in the human host makes both pathways very attractive as potential new
      targets for antimalarial drug development.

PMID- 15452113
TI  - The molecular basis of the differential subcellular localization of FYVE domains.
AB  - This study systematically analyzed the structural and mechanistic basis of the
      regulation of subcellular membrane targeting using FYVE domains as a model. FYVE
      domains, which mediate the recruitment of signaling and membrane-trafficking
      proteins to phosphatidylinositol 3-phosphate-containing endosomes, exhibit
      distinct subcellular localization despite minor structural variations within the
      family. Biophysical measurements, cellular imaging, and computational analysis of
      various FYVE domains showed that the introduction of a single cationic residue
      and a hydrophobic loop into the membrane binding region of the FYVE domains
      dramatically enhanced their membrane interactions. The results indicated that
      there is a threshold affinity for endosomal localization and that endosomal
      targeting of FYVE domains is sensitive to small changes in membrane affinity
      about this threshold. Collectively these studies provide new insight into how
      subcellular localization of FYVE domains and other membrane targeting domains can
      be regulated by minimal structural and environmental changes.

PMID- 15452114
TI  - Genome-wide analysis of pre-mRNA splicing: intron features govern the requirement
      for the second-step factor, Prp17 in Saccharomyces cerevisiae and
      Schizosaccharomyces pombe.
AB  - Removal of pre-mRNA introns is an essential step in eukaryotic genome
      interpretation. The spliceosome, a ribonucleoprotein performs this critical
      function; however, precise roles for many of its proteins remain unknown. Genome
      wide consequences triggered by the loss of a specific factor can elucidate its
      function in splicing and its impact on other cellular processes. We have employed
      splicing-sensitive DNA microarrays, with yeast open reading frames and intron
      sequences, to detect changes in splicing efficiency and global expression.
      Comparison of expression profiles, for intron-containing transcripts, among
      mutants of two second-step factors, Prp17 and Prp22, reveals their unique and
      shared effects on global splicing. This analysis enabled the identification of
      substrates dependent on Prp17. We find a significant Prp17 role in splicing of
      introns which are longer than 200nts and note its dispensability when introns
      have a < or =13-nucleotide spacing between their branch point nucleotide and 3 '
      splice site. In vitro splicing of substrates with varying branch nucleotide to 3
      ' splice site distances supports the differential Prp17 dependencies inferred
      from the in vivo analysis. Furthermore, we tested the predicted dispensability of
      Prp17 for splicing short introns in the evolutionarily distant yeast,
      Schizosaccharomyces pombe, where the genome contains predominantly short introns.
      SpPrp17 was non-essential at all growth temperatures implying that functional
      evolution of splicing factors is integrated with genome evolution. Together our
      studies point to a role for budding yeast Prp17 in splicing of subsets of introns
      and have predictive value for deciphering the functions of splicing factors in
      gene expression and regulation in other eukaryotes.

PMID- 15452115
TI  - P-O bond destabilization accelerates phosphoenzyme hydrolysis of sarcoplasmic
      reticulum Ca2+ -ATPase.
AB  - The phosphate group of the ADP-insensitive phosphoenzyme (E2-P) of sarcoplasmic
      reticulum Ca2+ -ATPase (SERCA1a) was studied with infrared spectroscopy to
      understand the high hydrolysis rate of E2-P. By monitoring an autocatalyzed
      isotope exchange reaction, three stretching vibrations of the transiently bound
      phosphate group were selectively observed against a background of 50,000 protein
      vibrations. They were found at 1194, 1137, and 1115 cm(-1). This information was
      evaluated using the bond valence model and empirical correlations. Compared with
      the model compound acetyl phosphate, structure and charge distribution of the E2
      P aspartyl phosphate resemble somewhat the transition state in a dissociative
      phosphate transfer reaction; the aspartyl phosphate of E2-P has 0.02 A shorter
      terminal P-O bonds and a 0.09 A longer bridging P-O bond that is approximately
      20% weaker, the angle between the terminal P-O bonds is wider, and -0.2 formal
      charges are shifted from the phosphate group to the aspartyl moiety. The weaker
      bridging P-O bond of E2-P accounts for a 10(11)-10(15)-fold hydrolysis rate
      enhancement, implying that P-O bond destabilization facilitates phosphoenzyme
      hydrolysis. P-O bond destabilization is caused by a shift of noncovalent
      interactions from the phosphate oxygens to the aspartyl oxygens. We suggest that
      the relative positioning of Mg2+ and Lys684 between phosphate and aspartyl
      oxygens controls the hydrolysis rate of the ATPase phosphoenzymes and related
      phosphoproteins.

PMID- 15452116
TI  - The mode of action of centrin. Binding of Ca2+ and a peptide fragment of Kar1p to
      the C-terminal domain.
AB  - Centrin is an EF-hand calcium-binding protein closely related to the prototypical
      calcium sensor protein calmodulin. It is found in microtubule-organizing centers
      of organisms ranging from algae and yeast to man. In vitro, the C-terminal domain
      of centrin binds to the yeast centrosomal protein Kar1p in a calcium-dependent
      manner, whereas the N-terminal domain does not show any appreciable affinity for
      Kar1p. To obtain deeper insights into the structural basis for centrin's
      function, we have characterized the affinities of the C-terminal domain of
      Chlamydomonas reinhardtii centrin for calcium and for a peptide fragment of Kar1p
      using CD, fluorescence, and NMR spectroscopy. Calcium binding site IV in C.
      reinhardtii centrin was found to bind Ca2+ approximately 100-fold more strongly
      than site III. In the absence of Ca2+, the protein occupies a mixture of closed
      conformations. Binding of a single ion in site IV is sufficient to radically
      alter the conformational equilibrium, promoting occupancy of an open
      conformation. However, an exchange between closed and open conformations remains
      even at saturating levels of Ca2+. The population of the open conformation is
      substantially stabilized by the presence of the target peptide Kar1p-(239-257) to
      a point where a single ion bound in site IV is sufficient to completely shift the
      conformational equilibrium to the open conformation. This is reflected in the
      enhancement of the Ca2+ affinity in this site by more than an order of magnitude.
      These data confirm the direct coupling of the Ca2+ binding-induced shift in the
      equilibrium between the closed and open conformations to the binding of the
      peptide. Combined with the common localization of the two proteins in the
      microtubule organizing center, our results suggest that centrin is constitutively
      bound to Kar1p through its C-terminal domain and that centrin's calcium sensor
      activities are mediated by the N-terminal domain.

PMID- 15452117
TI  - Taxol induces caspase-10-dependent apoptosis.
AB  - Taxol (paclitaxel) is known to inhibit cell growth and trigger significant
      apoptosis in various cancer cells. Although taxol induces apoptosis of cancer
      cells, its exact mechanism of action is not yet known. In this study we
      investigated death receptors, FAS-associated death domain protein (FADD), the
      activation of caspases-10 and -8 as well as the downstream caspases, and reactive
      oxygen species (ROS) in taxol-induced apoptosis in the CCRF-HSB-2 human
      lymphoblastic leukemia cell line. Pretreating the cells with neutralizing
      antibodies to Fas, tumor necrosis factor (TNF)-alpha receptor 1, or TNF-related
      apoptosis-inducing ligand receptors (DR4 and DR5) did not affect taxol-induced
      apoptosis, but transfection of the cells with a dominant negative FADD plasmid
      resulted in inhibition of taxol-induced apoptosis, revealing that taxol induces
      apoptosis independently of these death receptors but dependently on FADD.
      Furthermore, the drug induced activation of caspases-10, -8, -6, and -3, cleaved
      Bcl-2, Bid, poly(ADP-ribose) polymerase, and lamin B, and down-regulated cellular
      levels of FLICE-like inhibitory protein (FLIP) and X-chromosome-linked inhibitor
      of apoptosis protein (XIAP). However, despite the release of cytochrome c from
      the mitochondria in taxol-treated cells, caspase-9 was not activated. Inhibitors
      of caspases-8, -6, or -3 partially inhibited taxol-induced apoptosis, whereas the
      caspase-10 inhibitor totally abrogated this process. Taxol-induced apoptosis was
      also associated with decreased mitochondrial membrane potential (Deltapsim) and a
      significant increase in ROS generation. However, increased ROS production was not
      directly involved in taxol-triggered apoptosis. Therefore, these results
      demonstrate for the first time that taxol induces FADD-dependent apoptosis
      primarily through activation of caspase-10 but independently of death receptors.

PMID- 15452118
TI  - Translocation of Bim to the endoplasmic reticulum (ER) mediates ER stress
      signaling for activation of caspase-12 during ER stress-induced apoptosis.
AB  - Endoplasmic reticulum (ER) stress activates caspase-12 in murine cells,
      triggering the ER stress-specific cascade for implementation of apoptosis. In
      C2C12 murine myoblast cells, activation of the cascade occurs without release of
      cytochrome c from mitochondria, suggesting that the cascade is independent of
      mitochondrial damage. Stable overexpression of Bcl-xL in C2C12 cells suppressed
      activation of caspase-12 and apoptosis. In ER-stressed cells, but not in normal
      cells, Bcl-xL was co-immunoprecipitated with Bim, a pro-apoptotic member of the
      Bcl-2 family, suggesting that Bcl-xL sequesters Bim, thereby inhibiting the
      apoptotic signaling. Fractionation of C2C12 cells revealed that ER stress led to
      translocation of Bim from a dynein-rich compartment to the ER, while stable
      overexpression of Bcl-xL suppressed accumulation of Bim on the ER. Although the
      toxic effect of Bim had been previously observed only at the mitochondrial outer
      membrane, overexpression of a Bim derivative, Bim(ER), targeted at the surface of
      the ER led to apoptosis. A C2C12 transfectant overexpressing the caspase-12
      suppressor protein was resistant to Bim(ER), suggesting that the toxic effect of
      Bim on the ER is dependent on activation of caspase-12. Knockdown of Bim by RNA
      interference provided cells resistant to ER stress. These results suggest that
      translocation of Bim to the ER in response to ER stress is an important step
      toward activation of caspase-12 and initiation of the ER stress-specific caspase
      cascade.

PMID- 15452119
TI  - TetX is a flavin-dependent monooxygenase conferring resistance to tetracycline
      antibiotics.
AB  - The tetracycline antibiotics block microbial translation and constitute an
      important group of antimicrobial agents that find broad clinical utility.
      Resistance to this class of antibiotics is primarily the result of active efflux
      or ribosomal protection; however, a novel mechanism of resistance has been
      reported to be oxygen-dependent destruction of the drugs catalyzed by the enzyme
      TetX. Paradoxically, the tetX genes have been identified on transposable elements
      found in anaerobic bacteria of the genus Bacteroides. Overexpression of
      recombinant TetX in Escherichia coli followed by protein purification revealed a
      stoichiometric complex with flavin adenine dinucleotide. Reconstitution of in
      vitro enzyme activity demonstrated a broad tetracycline antibiotic spectrum and a
      requirement for molecular oxygen and NADPH in antibiotic degradation. The
      tetracycline products of TetX activity were unstable at neutral pH, but mass
      spectral and NMR characterization under acidic conditions supported initial
      monohydroxylation at position 11a followed by intramolecular cyclization and non
      enzymatic breakdown to other undefined products. TetX is therefore a FAD
      dependent monooxygenase. The enzyme not only catalyzed efficient degradation of a
      broad range of tetracycline analogues but also conferred resistance to these
      antibiotics in vivo. This is the first molecular characterization of an
      antibiotic-inactivating monooxygenase, the origins of which may lie in
      environmental bacteria.

PMID- 15452120
TI  - The C-terminal tails of tumor necrosis factor-related apoptosis-inducing ligand
      (TRAIL) and Fas receptors have opposing functions in Fas-associated death domain
      (FADD) recruitment and can regulate agonist-specific mechanisms of receptor
      activation.
AB  - Members of the tumor necrosis factor (TNF) superfamily of receptors such as
      Fas/CD95 and the TNF-related apoptosis-inducing ligand (TRAIL) receptors DR4 and
      DR5 induce apoptosis by recruiting adaptor molecules and caspases. The central
      adaptor molecule for these receptors is a death domain-containing protein, FADD,
      which binds to the activated receptor via death domain-death domain interactions.
      Here, we show that in addition to the death domain, the C-terminal tails of DR4
      and DR5 positively regulate FADD binding, caspase activation and apoptosis. In
      contrast, the corresponding region in the Fas receptor has the opposite effect
      and inhibits binding to the receptor death domain. Replacement of wild-type or
      mutant DR5 molecules into DR5-deficient BJAB cells indicates that some agonistic
      antibodies display an absolute requirement for the C-terminal tail for FADD
      binding and signaling while other antibodies can function in the absence of this
      mechanism. These data demonstrate that regions outside the death domains of DR4
      and DR5 have opposite effects to that of Fas in regulating FADD recruitment and
      show that different death receptor agonists can use distinct molecular mechanisms
      to activate signaling from the same receptor.

PMID- 15452121
TI  - A library of 7TM receptor C-terminal tails. Interactions with the proposed post
      endocytic sorting proteins ERM-binding phosphoprotein 50 (EBP50), N
      ethylmaleimide-sensitive factor (NSF), sorting nexin 1 (SNX1), and G protein
      coupled receptor-associated sorting protein (GASP).
AB  - Adaptor and scaffolding proteins determine the cellular targeting, the spatial,
      and thereby the functional association of G protein-coupled seven-transmembrane
      receptors with co-receptors, transducers, and downstream effectors and the
      adaptors determine post-signaling events such as receptor sequestration through
      interactions, mainly with the C-terminal intracellular tails of the receptors. A
      library of tails from 59 representative members of the super family of seven
      transmembrane receptors was probed as glutathione S-transferase fusion proteins
      for interactions with four different adaptor proteins previously proposed to be
      involved in post-endocytotic sorting of receptors. Of the two proteins suggested
      to target receptors for recycling to the cell membrane, which is the route
      believed to be taken by a majority of receptors, ERM (ezrin-radixin-moesin)
      binding phosphoprotein 50 (EBP50) bound only a single receptor tail, i.e. the
      beta(2)-adrenergic receptor, whereas N-ethylmaleimide-sensitive factor bound 11
      of the tail-fusion proteins. Of the two proteins proposed to target receptors for
      lysosomal degradation, sorting nexin 1 (SNX1) bound 10 and the C-terminal domain
      of G protein-coupled receptor-associated sorting protein bound 23 of the 59 tail
      proteins. Surface plasmon resonance analysis of the binding kinetics of selected
      hits from the glutathione S-transferase pull-down experiments, i.e. the tails of
      the virally encoded receptor US28 and the delta-opioid receptor, confirmed the
      expected nanomolar affinities for interaction with SNX1. Truncations of the NK(1)
      receptor revealed that an extended binding epitope is responsible for the
      interaction with both SNX1 and G protein-coupled receptor-associated sorting
      protein as well as with N-ethylmaleimide-sensitive factor. It is concluded that
      the tail library provides useful information on the general importance of certain
      adaptor proteins, for example, in this case, ruling out EBP50 as being a broad
      spectrum-recycling adaptor.

PMID- 15452122
TI  - The histone chaperone Asf1p mediates global chromatin disassembly in vivo.
AB  - The packaging of the eukaryotic genome into chromatin is likely to be mediated by
      chromatin assembly factors, including histone chaperones. We investigated the
      function of the histone H3/H4 chaperones anti-silencing function 1 (Asf1p) and
      chromatin assembly factor 1 (CAF-1) in vivo. Analysis of chromatin structure by
      accessibility to micrococcal nuclease and DNase I digestion demonstrated that the
      chromatin from CAF-1 mutant yeast has increased accessibility to these enzymes.
      In agreement, the supercoiling of the endogenous 2mu plasmid is reduced in yeast
      lacking CAF-1. These results indicate that CAF-1 mutant yeast globally under
      assemble their genome into chromatin, consistent with a role for CAF-1 in
      chromatin assembly in vivo. By contrast, asf1 mutants globally over-assemble
      their genome into chromatin, as suggested by decreased accessibility of their
      chromatin to micrococcal nuclease and DNase I digestion and increased
      supercoiling of the endogenous 2mu plasmid. Deletion of ASF1 causes a striking
      loss of acetylation on histone H3 lysine 9, but this is not responsible for the
      altered chromatin structure in asf1 mutants. These data indicate that Asf1p may
      have a global role in chromatin disassembly and an unexpected role in histone
      acetylation in vivo.

PMID- 15452123
TI  - Macrophage tropism of HIV-1 depends on efficient cellular dNTP utilization by
      reverse transcriptase.
AB  - Retroviruses utilize cellular dNTPs to perform proviral DNA synthesis in infected
      host cells. Unlike oncoretroviruses, which replicate in dividing cells,
      lentiviruses, such as human immunodeficiency virus type 1 (HIV-1) and simian
      immunodeficiency virus, are capable of efficiently replicating in non-dividing
      cells (terminally differentiated macrophages) as well as dividing cells (i.e.
      activated CD4+ T cells). In general, non-dividing cells are likely to have low
      cellular dNTP content compared with dividing cells. Here, by employing a novel
      assay for cellular dNTP content, we determined the dNTP concentrations in two HIV
      1 target cells, macrophages and activated CD4+ T cells. We found that human
      macrophages contained 130-250-fold lower dNTP concentrations than activated human
      CD4+ T cells. Biochemical analysis revealed that, unlike oncoretroviral reverse
      transcriptases (RTs), lentiviral RTs efficiently synthesize DNA even in the
      presence of the low dNTP concentrations equivalent to those found in macrophages.
      In keeping with this observation, HIV-1 vectors containing mutant HIV-1 RTs,
      which kinetically mimic oncoretroviral RTs, failed to transduce human macrophages
      despite retaining normal infectivity for activated CD4+ T cells and other
      dividing cells. These results suggest that the ability of HIV-1 to infect
      macrophages, which is essential to establishing the early pathogenesis of HIV-1
      infection, depends, at least in part, on enzymatic adaptation of HIV-1 RT to
      efficiently catalyze DNA synthesis in limited cellular dNTP substrate
      environments.

PMID- 15452124
TI  - The use of forced protein evolution to investigate and improve stability of
      family 10 xylanases. The production of Ca2+-independent stable xylanases.
AB  - Metal ions such as calcium often play a key role in protein thermostability. The
      inclusion of metal ions in industrial processes is, however, problematic. Thus,
      the evolution of enzymes that display enhanced stability, which is not reliant on
      divalent metals, is an important biotechnological goal. Here we have used forced
      protein evolution to interrogate whether the stabilizing effect of calcium in an
      industrially relevant enzyme can be replaced with amino acid substitutions. Our
      study has focused on the GH10 xylanase CjXyn10A from Cellvibrio japonicus, which
      contains an extended calcium binding loop that confers proteinase resistance and
      thermostability. Three rounds of error-prone PCR and selection identified a
      treble mutant, D262N/A80T/R347C, which in the absence of calcium is more
      thermostable than wild type CjXyn10A bound to the divalent metal. D262N
      influences the properties of the calcium binding site, A80T fills a cavity in the
      enzyme, increasing the number of hydrogen bonds and van der Waals interactions,
      and the R347C mutation introduces a disulfide bond that decreases the free energy
      of the unfolded enzyme. A derivative of CjXyn10A (CfCjXyn10A) in which the
      calcium binding loop has been replaced with a much shorter loop from Cellulomonas
      fimi CfXyn10A was also subjected to forced protein evolution to select for
      thermostablizing mutations. Two amino acid substitutions within the introduced
      loop and the A80T mutation increased the thermostability of the enzyme. This
      study demonstrates how forced protein evolution can be used to introduce enhanced
      stability into industrially relevant enzymes while removing calcium as a major
      stability determinant.

PMID- 15452125
TI  - Determinants of the t peptide involved in folding, degradation, and secretion of
      acetylcholinesterase.
AB  - The C-terminal 40-residue t peptide of acetylcholinesterase (AChE) forms an
      amphiphilic alpha helix with a cluster of seven aromatic residues. It allows
      oligomerization and induces a partial degradation of AChE subunits through the
      endoplasmic reticulum-associated degradation pathway. We show that the t peptide
      induces the misfolding of a fraction of AChE subunits, even when mutations
      disorganized the cluster of aromatic residues or when these residues were
      replaced by leucines, indicating that this effect is due to hydrophobic residues.
      Mutations in the aromatic-rich region affected the cellular fate of AChE in a
      similar manner, with or without mutations that prevented dimerization.
      Degradation was decreased and secretion was increased when aromatic residues were
      replaced by leucines, and the opposite occurred when the amphiphilic alpha helix
      was disorganized. The last two residues (Asp-Leu) somewhat resembled an
      endoplasmic reticulum retention signal and caused a partial retention but only in
      mutants possessing aromatic residues in their t peptide. Our results suggested
      that several "signals" in the catalytic domain and in the t peptide act
      cooperatively for AChE quality control.

PMID- 15452126
TI  - Nuclear matrix interactions at the human protamine domain: a working model of
      potentiation.
AB  - The compact eukaryotic genome must be selectively opened to grant trans-factor
      access to cis-regulatory elements to overcome the primary barrier to gene
      transcription. The mechanism that governs the selective opening of chromatin
      domains (i.e. potentiation) remains poorly understood. In the absence of a well
      defined locus control region, the nuclear matrix is considered the primary
      candidate regulating the opening of the multigenic PRM1 --> PRM2 --> TNP2 human
      protamine domain. To directly examine its role, four lines of transgenic mice
      with different configurations of flanking nuclear matrix attachment regions
      (MARs) encompassing the protamine domain were created. We show that upon removal
      of the MARs, the locus becomes subject to position effects. The 3' MAR alone may
      be sufficient to protect against silencing. In concert, the MARs bounding this
      domain likely synergize to regulate the expression of the various members of this
      gene cluster. Interestingly, the MARs may convey a selective reproductive
      advantage, such that constructs bearing both 5' and 3' MARs are passed to their
      offspring with greater frequency. Thus, the MARs bounding the PRM1 --> PRM2 -->
      TNP2 protamine domain have many and varied functions.

PMID- 15452127
TI  - srf-3, a mutant of Caenorhabditis elegans, resistant to bacterial infection and
      to biofilm binding, is deficient in glycoconjugates.
AB  - srf-3 is a mutant of C. elegans that is resistant to infection by Microbacterium
      nematophilum and to binding of the biofilm produced by Yersinia
      pseudotuberculosis and Yersinia pestis. Recently, SRF-3 was characterized as a
      nucleotide sugar transporter of the Golgi apparatus occurring exclusively in
      hypodermal seam cells, pharyngeal cells, and spermatheca. Based on the above
      observations, we hypothesized that srf-3 may have altered glyconjugates that may
      enable the mutant nematode to grow unaffected in the presence of the above
      pathogenic bacteria. Following analyses of N- and O-linked glycoconjugates of srf
      3 and wild type nematodes using a combination of enzymatic degradation,
      permethylation, and mass spectrometry, we found in srf-3 a 65% reduction of
      acidic O-linked glycoconjugates containing glucuronic acid and galactose as well
      as a reduction of N-linked glycoconjugates containing galactose and fucose. These
      results are consistent with the specificity of SRF-3 for UDP-galactose and
      strongly suggest that the above glycoconjugates play an important role in
      allowing adhesion of M. nematophilum or Y. pseudotuberculosis biofilm to wild
      type C. elegans. Furthermore, because seam cells as well as pharyngeal cells
      secrete their glycoconjugates to the cuticle and surrounding surfaces, the
      results also demonstrate the critical role of these cells and their secreted
      glycoproteins in nematode-bacteria interactions and offer a mechanistic basis for
      strategies to block such recognition processes.

PMID- 15452128
TI  - Altered amyloid-beta metabolism and deposition in genomic-based beta-secretase
      transgenic mice.
AB  - Amyloid-beta (Abeta) the primary component of the senile plaques found in
      Alzheimer's disease (AD) is generated by the rate-limiting cleavage of amyloid
      precursor protein (APP) by beta-secretase followed by gamma-secretase cleavage.
      Identification of the primary beta-secretase gene, BACE1, provides a unique
      opportunity to examine the role this unique aspartyl protease plays in altering
      Abeta metabolism and deposition that occurs in AD. The current experiments seek
      to examine how modulating beta-secretase expression and activity alters APP
      processing and Abeta metabolism in vivo. Genomic-based BACE1 transgenic mice were
      generated that overexpress human BACE1 mRNA and protein. The highest expressing
      BACE1 transgenic line was mated to transgenic mice containing human APP
      transgenes. Our biochemical and histochemical studies demonstrate that mice
      overexpressing both BACE1 and APP show specific alterations in APP processing and
      age-dependent Abeta deposition. We observed elevated levels of Abeta isoforms as
      well as significant increases of Abeta deposits in these double transgenic
      animals. In particular, the double transgenics exhibited a unique cortical
      deposition profile, which is consistent with a significant increase of BACE1
      expression in the cortex relative to other brain regions. Elevated BACE1
      expression coupled with increased deposition provides functional evidence for
      beta-secretase as a primary effector in regional amyloid deposition in the AD
      brain. Our studies demonstrate, for the first time, that modulation of BACE1
      activity may play a significant role in AD pathogenesis in vivo.

PMID- 15452129
TI  - Identification of the MMRN1 binding region within the C2 domain of human factor
      V.
AB  - In platelets, coagulation cofactor V is stored in complex with multimerin 1 in
      alpha-granules for activation-induced release during clot formation. The
      molecular nature of multimerin 1 factor V binding has not been determined,
      although multimerin 1 is known to interact with the factor V light chain. We
      investigated the region in factor V important for multimerin 1 binding using
      modified enzyme-linked immunoassays and recombinant factor V constructs. Factor V
      constructs lacking the C2 region or entire light chain had impaired and absent
      multimerin 1 binding, respectively, whereas the B domain deleted construct had
      modestly reduced binding. Analyses of point mutated constructs indicated that the
      multimerin 1 binding site in the C2 domain of factor V partially overlaps the
      phosphatidylserine binding site and that the factor V B domain enhances
      multimerin 1 binding. Multimerin 1 did not inhibit factor V phosphatidylserine
      binding, and it bound to phosphatidylserine independently of factor V. There was
      a reduction in factor V in complex with multimerin 1 after activation, and
      thrombin cleavage significantly reduced factor V binding to multimerin 1. In
      molar excess, multimerin 1 minimally reduced factor V procoagulant activity in
      prothrombinase assays and only if it was added before factor V activation. The
      dissociation of factor V-multimerin 1 complexes following factor V activation
      suggests a role for multimerin 1 in delivering and localizing factor V onto
      platelets prior to prothrombinase assembly.

PMID- 15452130
TI  - Cholesterol and 25-hydroxycholesterol inhibit activation of SREBPs by different
      mechanisms, both involving SCAP and Insigs.
AB  - The current paper demonstrates that cholesterol and its hydroxylated derivative,
      25-hydroxycholesterol (25-HC), inhibit cholesterol synthesis by two different
      mechanisms, both involving the proteins that control sterol regulatory element
      binding proteins (SREBPs), membrane-bound transcription factors that activate
      genes encoding enzymes of lipid synthesis. Using methyl-beta-cyclodextrin as a
      delivery vehicle, we show that cholesterol enters cultured Chinese hamster ovary
      cells and elicits a conformational change in SREBP cleavage-activating protein
      (SCAP), as revealed by the appearance of a new fragment in tryptic digests. This
      change causes SCAP to bind to Insigs, which are endoplasmic reticulum retention
      proteins that abrogate movement of the SCAP.SREBP complex to the Golgi apparatus
      where SREBPs are normally processed to their active forms. Direct binding of
      cholesterol to SCAP in intact cells was demonstrated by showing that a
      photoactivated derivative of cholesterol cross-links to the membrane domain of
      SCAP. The inhibitory actions of cholesterol do not require the isooctyl side
      chain or the Delta5-double bond of cholesterol, but they do require the 3beta
      hydroxyl group. 25-HC is more potent than cholesterol in eliciting SCAP binding
      to Insigs, but 25-HC does not cause a detectable conformational change in SCAP.
      Moreover, a photoactivated derivative of 25-HC does not cross-link to SCAP. These
      data imply that cholesterol interacts with SCAP directly by inducing it to bind
      to Insigs, whereas 25-HC works indirectly through a putative 25-HC sensor protein
      that elicits SCAP-Insig binding.

PMID- 15452131
TI  - Sodium channel beta1 subunits promote neurite outgrowth in cerebellar granule
      neurons.
AB  - Many immunoglobulin superfamily members are integral in development through
      regulation of processes such as growth cone guidance, cell migration, and neurite
      outgrowth. We demonstrate that homophilic interactions between voltage-gated
      sodium channel beta1 subunits promote neurite extension in cerebellar granule
      neurons. Neurons isolated from wild-type or beta1(-/-) mice were plated on top of
      parental, mock-, or beta1-transfected fibroblasts. Wild-type neurons consistently
      showed increased neurite length when grown on beta1-transfected monolayers,
      whereas beta1(-/-) neurons showed no increase compared with control conditions.
      beta1-mediated neurite extension was mimicked using a soluble beta1 extracellular
      domain and was blocked by antibodies directed against the beta1 extracellular
      domain. Immunohistochemical analysis suggests that the beta1 and beta4 subunits,
      but not beta2 and beta3, are expressed in cerebellar Bergmann glia as well as
      granule neurons. These results suggest a novel role for beta1 during neuronal
      development and are the first demonstration of a functional role for sodium
      channel beta subunit-mediated cell adhesive interactions.

PMID- 15452132
TI  - Fibrillar amyloid-beta peptides kill human primary neurons via NADPH oxidase
      mediated activation of neutral sphingomyelinase. Implications for Alzheimer's
      disease.
AB  - Alzheimer's disease is a major illness of dementia characterized by the presence
      of amyloid plaques, neurofibrillary tangles, and extensive neuronal apoptosis.
      However, the mechanism behind neuronal apoptosis in the Alzheimer's-diseased
      brain is poorly understood. This study underlines the importance of neutral
      sphingomyelinase in fibrillar Abeta peptide-induced apoptosis and cell death in
      human primary neurons. Abeta1-42 peptides induced the activation of
      sphingomyelinases and the production of ceramide in neurons. Interestingly,
      neutral (N-SMase), but not acidic (A-SMase), sphingomyelinase was involved in
      Abeta1-42-mediated neuronal apoptosis and cell death. Abeta1-42-induced
      production of ceramide was redox-sensitive, as reactive oxygen species were
      involved in the activation of N-SMase but not A-SMase. Abeta1-42 peptides induced
      the NADPH oxidase-mediated production of superoxide radicals in neurons that was
      involved in the activation of N-SMase, but not A-SMase, via hydrogen peroxide.
      Consistently, superoxide radicals generated by hypoxanthine and xanthine oxidase
      also induced the activation of N-SMase, but not A-SMase, through a catalase
      sensitive pathway. Furthermore, antisense knockdown of p22phox, a subunit of
      NADPH oxidase, inhibited Abeta1-42-induced neuronal apoptosis and cell death.
      These studies suggest that fibrillar Abeta1-42 peptides induce neuronal apoptosis
      through the NADPH oxidase-superoxide-hydrogen peroxide-NS-Mase-ceramide pathway.

PMID- 15452133
TI  - A cyclic peptide mimicking the third intracellular loop of the V2 vasopressin
      receptor inhibits signaling through its interaction with receptor dimer and G
      protein.
AB  - In this study, we investigated the mechanism by which a peptide mimicking the
      third cytoplasmic loop of the vasopressin V2 receptor inhibits signaling. This
      loop was synthesized as a cyclic peptide (i3 cyc) that adopted defined secondary
      structure in solution. We found that i3 cyc inhibited the adenylyl cyclase
      activity induced by vasopressin or a nonhydrolyzable analog of GTP, guanosine 5'
      O-(3-thio)triphosphate. This peptide also affected the specific binding of
      [3H]AVP by converting vasopressin binding sites from a high to a low affinity
      state without any effect on the global maximal binding capacity. The inhibitory
      actions of i3 cyc could also be observed in the presence of maximally uncoupling
      concentration of guanosine 5'-O-(3-thio)triphosphate, indicating a direct effect
      on the receptor itself and not exclusively on the interaction between the Gs
      protein and the V2 receptor (V2-R). Bioluminescence resonance energy-transfer
      experiments confirmed this assumption, because i3 cyc induced a significant
      inhibition of the bioluminescence resonance energy-transfer signal between the
      Renilla reniformis luciferase and the enhanced yellow fluorescent protein fused
      V2-R. This suggests that the proper arrangement of the dimer could be an
      important prerequisite for triggering Gs protein activation. In addition to its
      effect on the receptor itself, the peptide exerted some of its actions at the G
      protein level, because it could also inhibit guanosine 5'-O-(3-thio)triphosphate
      stimulated AC activity. Taken together, the data demonstrate that a peptide
      mimicking V2-R third intracellular loop affects both the dimeric structural
      organization of the receptor and has direct inhibitory action on Gs.

PMID- 15452134
TI  - GPI7 involved in glycosylphosphatidylinositol biosynthesis is essential for yeast
      cell separation.
AB  - GPI7 is involved in adding ethanolaminephosphate to the second mannose in the
      biosynthesis of glycosylphosphatidylinositol (GPI) in Saccharomyces cerevisiae.
      We isolated gpi7 mutants, which have defects in cell separation and a daughter
      cell-specific growth defect at the non-permissive temperature. WSC1, RHO2, ROM2,
      GFA1, and CDC5 genes were isolated as multicopy suppressors of gpi7-2 mutant.
      Multicopy suppressors could suppress the growth defect of gpi7 mutants but not
      the cell separation defect. Loss of function mutations of genes involved in the
      Cbk1p-Ace2p pathway, which activates the expression of daughter-specific genes
      for cell separation after cytokinesis, bypassed the temperature-sensitive growth
      defect of gpi7 mutants. Furthermore, deletion of EGT2, one of the genes
      controlled by Ace2p and encoding a GPI-anchored protein required for cell
      separation, ameliorated the temperature sensitivity of the gpi7 mutant. In this
      mutant, Egt2p was displaced from the septal region to the cell cortex, indicating
      that GPI7 plays an important role in cell separation via the GPI-based
      modification of daughter-specific proteins in S. cerevisiae.

PMID- 15452135
TI  - Hiding behind hydrophobicity. Transmembrane segments in mass spectrometry.
AB  - Proteomics of membrane proteins is essential for the understanding of cellular
      function. However, mass spectrometric analysis of membrane proteomes has been
      less successful than the proteomic determination of soluble proteins. To
      elucidate the mystery of transmembrane proteins in mass spectrometry, we present
      a detailed statistical analysis of experimental data derived from chloroplast
      membranes. This approach was further accomplished by the analysis of the
      Arabidopsis thaliana proteome after in silico digestion. We demonstrate that both
      the length and the hydrophobicity of the proteolytic fragments containing
      transmembrane segments are major determinants for detection by mass spectrometry.
      Based on a comparative analysis, we discuss possibilities to overcome the problem
      and provide possible protocols to shift the hydrophobicity of transmembrane
      segment-containing peptides to facilitate their detection.

PMID- 15452136
TI  - Molecular and biochemical characterization of the Skp2-Cks1 binding interface.
AB  - SCF(Skp2) is a multisubunit E3 ubiquitin ligase responsible for ubiquitination of
      cell cycle inhibitor p27. Ubiquitination of p27 requires an adapter protein,
      Cks1, to be in direct association with Skp2. The exact interface between Skp2 and
      Cks1 has not been elucidated. Here we have reported the definition of the
      critical functional interface between Skp2 and Cks1. We have identified eight
      amino acid residues in two discrete regions of Skp2 that are engaged in Cks1
      binding. Mutation of any of these eight residues alone or in combination results
      in the loss of Cks1 association and negates Skp2-dependent p27 ubiquitination.
      These eight amino acid residues map on the same side of the Skp2 structure and
      likely constitute a functional binding surface for Cks1. Four of the eight amino
      acid residues are located in the largely unstructured carboxyl-terminal tail
      region of Skp2. These results uncovered the specificity of the Skp2-Cks1
      interaction and reveal a critical function for the structurally flexible carboxyl
      terminal tail region of Skp2 in Cks1 recognition and substrate ubiquitination.

PMID- 15452137
TI  - Intact RNA-binding domains are necessary for structure-specific DNA binding and
      transcription control by CBTF122 during Xenopus development.
AB  - CBTF122 is a subunit of the Xenopus CCAAT box transcription factor complex and a
      member of a family of double-stranded RNA-binding proteins that function in both
      transcriptional and post-transcriptional control. Here we identify a region of
      CBTF122 containing the double-stranded RNA-binding domains that is capable of
      binding either RNA or DNA. We show that these domains bind A-form DNA in
      preference to B-form DNA and that the -59 to -31 region of the GATA-2 promoter
      (an in vivo target of CCAAT box transcription factor) adopts a partial A-form
      structure. Mutations in the RNA-binding domains that inhibit RNA binding also
      affect DNA binding in vitro. In addition, these mutations alter the ability of
      CBTF122 fusions with engrailed transcription repressor and VP16 transcription
      activator domains to regulate transcription of the GATA-2 gene in vivo. These
      data support the hypothesis that the double-stranded RNA-binding domains of this
      family of proteins are important for their DNA binding both in vitro and in vivo.

PMID- 15452138
TI  - The mechanism of spindle assembly: functions of Ran and its target TPX2.
AB  - Recent work has provided new insights into the mechanism of spindle assembly.
      Growing evidence supports a model in which the small GTPase Ran plays a central
      role in this process. Here, we examine the evidence for the existence of a RanGTP
      gradient around mitotic chromosomes and some controversial data on the role that
      chromosomes play in spindle assembly. We review the current knowledge on the Ran
      downstream targets for spindle assembly and we focus on the multiple roles of
      TPX2, one of the targets of RanGTP during cell division.

PMID- 15452139
TI  - Regulation of WASP/WAVE proteins: making a long story short.
AB  - Despite their homology, the regulation of WASP and WAVE, activators of Arp2/3
      dependent actin polymerization, has always been thought to be different. Several
      recent studies have revealed new aspects of their regulation, highlighting its
      complexity and the crucial role of post-translational modifications. New data
      also suggest additional functions for WASP family proteins, pushing us to
      reconsider existing models.

PMID- 15452140
TI  - Nuclear export of OLIG2 in neural stem cells is essential for ciliary
      neurotrophic factor-induced astrocyte differentiation.
AB  - Neural stem cell (NSC) differentiation is precisely controlled by a network of
      transcription factors, which themselves are regulated by extracellular signals
      (Bertrand, N., D.S. Castro, and F. Guillemot, 2002. Nat. Rev. Neurosci 3:517-530;
      Shirasaki, R. and S.L. Pfaff, 2002. Annu. Rev. Neurosci 25:251-281). One way that
      the activity of such transcription factors is controlled is by the regulation of
      their movement between the cytosol and nucleus (Vandromme, M., C. Gauthier
      Rouviere, N. Lamb, and A. Fernandez, 1996. Trends Biochem.Sci. 21:59-64; Lei,
      E.P. and P.A. Silver, 2002. Dev. Cell 2:261-272). Here we show that the basic
      helix-loop-helix transcription factor OLIG2, which has been shown to be required
      for motor neuron and oligodendrocyte development, is found in the cytoplasm, but
      not the nucleus, of astrocytes in culture and of a subset of astrocytes in the
      subventricular zone. We demonstrate that the accumulation of OLIG2 in the nucleus
      of NSCs blocks the CNTF-induced astrocyte differentiation and that the
      translocation of OLIG2 to the cytoplasm is promoted by activated AKT. We propose
      that the AKT-stimulated export of OLIG2 from the nucleus of NSCs is essential for
      the astrocyte differentiation.

PMID- 15452141
TI  - STAT3 noncell-autonomously controls planar cell polarity during zebrafish
      convergence and extension.
AB  - Zebrafish signal transducer and activator of transcription 3 (STAT3) controls the
      cell movements during gastrulation. Here, we show that noncell-autonomous
      activity of STAT3 signaling in gastrula organizer cells controls the polarity of
      neighboring cells through Dishevelled-RhoA signaling in the Wnt-planar cell
      polarity (Wnt-PCP) pathway. In STAT3-depleted embryos, although all the known
      molecules in the Wnt-PCP pathway were expressed normally, the RhoA activity in
      lateral mesendodermal cells was down-regulated, resulting in severe cell
      polarization defects in convergence and extension movements identical to
      Strabismus-depleted embryos. Cell-autonomous activation of Wnt-PCP signaling by
      DeltaN-dishevelled rescued the defect in cell elongation, but not the orientation
      of lateral mesendodermal cells in STAT3-depleted embryos. The defect in the
      orientation could be rescued by transplantation of shield cells having noncell
      autonomous activity of STAT3 signaling. These results suggest that the cells
      undergoing convergence and extension movement may sense the gradient of signaling
      molecules, which are expressed in gastrula organizer by STAT3 and noncell
      autonomously activate PCP signaling in neighboring cells during zebrafish
      gastrulation.

PMID- 15452142
TI  - Loss of KLP-19 polar ejection force causes misorientation and missegregation of
      holocentric chromosomes.
AB  - Holocentric chromosomes assemble kinetochores along their length instead of at a
      focused spot. The elongated expanse of an individual holocentric kinetochore and
      its potential flexibility heighten the risk of stable attachment to microtubules
      from both poles of the mitotic spindle (merotelic attachment), and hence aberrant
      segregation of chromosomes. Little is known about the mechanisms that holocentric
      species have evolved to avoid this type of error. Our studies of the influence of
      KLP-19, an essential microtubule motor, on the behavior of holocentric
      Caenorhabditis elegans chromosomes suggest that it has a major role in combating
      merotelic attachments. Depletion of KLP-19, which associates with nonkinetochore
      chromatin, allows aberrant poleward chromosome motion during prometaphase,
      misalignment of holocentric kinetochores, and multiple anaphase chromosome
      bridges in all mitotic divisions. Time-lapse movies of GFP-labeled mono- and
      bipolar spindles demonstrate that KLP-19 generates a force on relatively stiff
      holocentric chromosomes that pushes them away from poles. We hypothesize that
      this polar ejection force minimizes merotelic misattachment by maintaining a
      constant tension on pole-kinetochore connections throughout prometaphase, tension
      that compels sister kinetochores to face directly toward opposite poles.

PMID- 15452143
TI  - Detection of snRNP assembly intermediates in Cajal bodies by fluorescence
      resonance energy transfer.
AB  - Spliceosomal small nuclear ribonucleoprotein particles (snRNPs) are required for
      pre-mRNA splicing throughout the nucleoplasm, yet snRNPs also concentrate in
      Cajal bodies (CBs). To address a proposed role of CBs in snRNP assembly, we have
      used fluorescence resonance energy transfer (FRET) microscopy to investigate the
      subnuclear distribution of specific snRNP intermediates. Two distinct complexes
      containing the protein SART3 (p110), required for U4/U6 snRNP assembly, were
      localized: SART3.U6 snRNP and SART3.U4/U6 snRNP. These complexes segregated to
      different nuclear compartments, with SART3.U6 snRNPs exclusively in the
      nucleoplasm and SART3.U4/U6 snRNPs preferentially in CBs. Mutant cells lacking
      the CB-specific protein coilin and consequently lacking CBs exhibited increased
      nucleoplasmic levels of SART3.U4/U6 snRNP complexes. Reconstitution of CBs in
      these cells by expression of exogenous coilin restored accumulation of
      SART3.U4/U6 snRNP in CBs. Thus, while some U4/U6 snRNP assembly can occur in the
      nucleoplasm, these data provide evidence that SART3.U6 snRNPs form in the
      nucleoplasm and translocate to CBs where U4/U6 snRNP assembly occurs.

PMID- 15452144
TI  - Endophilin B1 is required for the maintenance of mitochondrial morphology.
AB  - We report that a fatty acyl transferase, endophilin B1, is required for
      maintenance of mitochondrial morphology. Down-regulation of this protein or
      overexpression of endophilin B1 lacking the NH(2)-terminal lipid-modifying domain
      causes striking alterations of the mitochondrial distribution and morphology.
      Dissociation of the outer mitochondrial membrane compartment from that of the
      matrix, and formation of vesicles and tubules of outer mitochondrial membrane,
      was also observed in both endophilin B1 knockdown cells and after overexpression
      of the truncated protein, indicating that endophilin B1 is required for the
      regulation of the outer mitochondrial membrane dynamics. We also show that
      endophilin B1 translocates to the mitochondria during the synchronous remodeling
      of the mitochondrial network that has been described to occur during apoptosis.
      Double knockdown of endophilin B1 and Drp1 leads to a mitochondrial phenotype
      identical to that of the Drp1 single knockdown, a result consistent with Drp1
      acting upstream of endophilin B1 in the maintenance of morphological dynamics of
      mitochondria.

PMID- 15452146
TI  - Superoxide is a mediator of an altruistic aging program in Saccharomyces
      cerevisiae.
AB  - Aging is believed to be a nonadaptive process that escapes the force of natural
      selection. Here, we challenge this dogma by showing that yeast laboratory strains
      and strains isolated from grapes undergo an age- and pH-dependent death with
      features of mammalian programmed cell death (apoptosis). After 90-99% of the
      population dies, a small mutant subpopulation uses the nutrients released by dead
      cells to grow. This adaptive regrowth is inversely correlated with protection
      against superoxide toxicity and life span and is associated with elevated age
      dependent release of nutrients and increased mutation frequency. Computational
      simulations confirm that premature aging together with a relatively high mutation
      frequency can result in a major advantage in adaptation to changing environments.
      These results suggest that under conditions that model natural environments,
      yeast organisms undergo an altruistic and premature aging and death program,
      mediated in part by superoxide. The role of similar pathways in the regulation of
      longevity in organisms ranging from yeast to mice raises the possibility that
      mammals may also undergo programmed aging.

PMID- 15452145
TI  - Presenilin 1 mediates the turnover of telencephalin in hippocampal neurons via an
      autophagic degradative pathway.
AB  - Presenilin 1 (PS1) interacts with telencephalin (TLN) and the amyloid precursor
      protein via their transmembrane domain (Annaert, W.G., C. Esselens, V. Baert, C.
      Boeve, G. Snellings, P. Cupers, K. Craessaerts, and B. De Strooper. 2001. Neuron.
      32:579-589). Here, we demonstrate that TLN is not a substrate for gamma-secretase
      cleavage, but displays a prolonged half-life in PS1(-/-) hippocampal neurons. TLN
      accumulates in intracellular structures bearing characteristics of autophagic
      vacuoles including the presence of Apg12p and LC3. Importantly, the TLN
      accumulations are suppressed by adenoviral expression of wild-type, FAD-linked
      and D257A mutant PS1, indicating that this phenotype is independent from gamma
      secretase activity. Cathepsin D deficiency also results in the localization of
      TLN to autophagic vacuoles. TLN mediates the uptake of microbeads concomitant
      with actin and PIP2 recruitment, indicating a phagocytic origin of TLN
      accumulations. Absence of endosomal/lysosomal proteins suggests that the TLN
      positive vacuoles fail to fuse with endosomes/lysosomes, preventing their
      acidification and further degradation. Collectively, PS1 deficiency affects in a
      gamma-secretase-independent fashion the turnover of TLN through autophagic
      vacuoles, most likely by an impaired capability to fuse with lysosomes.

PMID- 15452147
TI  - Regulation of Notch signaling by Drosophila heparan sulfate 3-O sulfotransferase.
AB  - Heparan sulfate (HS) regulates the activity of various ligands and is involved in
      molecular recognition events on the cell surface and in the extracellular matrix.
      Specific binding of HS to different ligand proteins depends on the sulfation
      pattern of HS. For example, the interaction between antithrombin and a particular
      3-O sulfated HS motif is thought to modulate blood coagulation. However, a recent
      study of mice defective for this modification suggested that 3-O sulfation plays
      other biological roles. Here, we show that Drosophila melanogaster HS 3-O
      sulfotransferase-b (Hs3st-B), which catalyzes HS 3-O sulfation, is a novel
      component of the Notch pathway. Reduction of Hs3st-B function by transgenic RNA
      interference compromised Notch signaling, producing neurogenic phenotypes. We
      also show that levels of Notch protein on the cell surface were markedly
      decreased by loss of Hs3st-B. These findings suggest that Hs3st-B is involved in
      Notch signaling by affecting stability or intracellular trafficking of Notch
      protein.

PMID- 15452148
TI  - CD44 modulates Smad1 activation in the BMP-7 signaling pathway.
AB  - Bone morphogenetic protein 7 (BMP-7) regulates cellular metabolism in embryonic
      and adult tissues. Signal transduction occurs through the activation of
      intracellular Smad proteins. In this paper, using a yeast two-hybrid screen,
      Smad1 was found to interact with the cytoplasmic domain of CD44, a receptor for
      the extracellular matrix macromolecule hyaluronan. Coimmunoprecipitation
      experiments confirmed the interaction of Smad1 with full-length CD44-interactions
      that did not occur when CD44 receptors truncated within the cytoplasmic domain
      were tested. Chondrocytes overexpressing a truncated CD44 on a background of
      endogenous full-length CD44 no longer exhibited Smad1 nuclear translocation upon
      BMP-7 stimulation. Further, pretreatment of chondrocytes with Streptomyces
      hyaluronidase to disrupt extracellular hyaluronan-cell interactions inhibited BMP
      7-mediated Smad1 phosphorylation, nuclear translocation of Smad1 or Smad4, and
      SBE4-luciferase reporter activation. These results support a functional link
      between the BMP signaling cascade and CD44. Thus, changes in hyaluronan-cell
      interactions may serve as a means to modulate cellular responsiveness to BMP.

PMID- 15452149
TI  - Conversion of ES cells to columnar epithelia by hensin and to squamous epithelia
      by laminin.
AB  - Single-layered epithelia are the first differentiated cell types to develop in
      the embryo, with columnar and squamous types appearing immediately after
      blastocyst implantation. Here, we show that mouse embryonic stem cells seeded on
      hensin or laminin, but not fibronectin or collagen type IV, formed hemispheric
      epithelial structures whose outermost layer terminally differentiated to an
      epithelium that resembled the visceral endoderm. Hensin induced columnar
      epithelia, whereas laminin formed squamous epithelia. At the egg cylinder stage,
      the distal visceral endoderm is columnar, and these cells begin to migrate
      anteriorly to create the anterior visceral endoderm, which assumes a squamous
      shape. Hensin expression coincided with the dynamic appearance and disappearance
      of columnar cells at the egg cylinder stage of the embryo. These expression
      patterns, and the fact that hensin null embryos (and those already reported for
      laminin) die at the onset of egg cylinder formation, support the view that hensin
      and laminin are required for terminal differentiation of columnar and squamous
      epithelial phenotypes during early embryogenesis.

PMID- 15452150
TI  - The role of hypoxia inducible factor 1 (HIF-1) in hypoxia induced apoptosis.
AB  - Apoptosis can be induced in response to hypoxia. The severity of hypoxia
      determines whether cells become apoptotic or adapt to hypoxia and survive. A
      hypoxic environment devoid of nutrients prevents the cell undergoing energy
      dependent apoptosis and cells become necrotic. Apoptosis regulatory proteins are
      delicately balanced. In solid tumours, hypoxia is a common phenomenon. Cells
      adapt to this environmental stress, so that after repeated periods of hypoxia,
      selection for resistance to hypoxia induced apoptosis occurs. These resistant
      tumours probably have a more aggressive phenotype and may have decreased
      responsiveness to treatment. The key regulator of this process, hypoxia inducible
      factor 1 (HIF-1), can initiate apoptosis by inducing high concentrations of
      proapoptotic proteins, such as BNIP3, and can cause stabilisation of p53.
      However, during hypoxia, antiapoptotic proteins, such as IAP-2, can be induced,
      whereas the proapoptotic protein Bax can be downregulated. During hypoxia, an
      intricate balance exists between factors that induce or counteract apoptosis, or
      even stimulate proliferation. Understanding the regulation of apoptosis during
      hypoxia and the mechanisms of resistance to apoptosis might lead to more specific
      treatments for solid tumours.

PMID- 15452152
TI  - Chemical pathology and the new contract for GPs.

PMID- 15452151
TI  - Mucosal immunology of vaccines against pathogenic nasopharyngeal bacteria.
AB  - The introduction of Haemophilus influenzae type b conjugate vaccines during the
      1990s was followed by dramatic decreases both in the incidence of Haemophilus
      influenzae type b related invasive disease and in nasopharyngeal carriage of the
      organism. The extent of this effect has been influenced by the fact that
      Haemophilus influenzae type b conjugate vaccines reduce nasopharyngeal carriage
      and induce herd immunity. Based on the success of Haemophilus influenzae type b
      conjugate vaccines, chemical conjugation has been applied to the development of
      pneumococcal and meningococcal polysaccharide conjugate vaccines. Evidence has
      begun to accumulate that these new polysaccharide based conjugate vaccines can
      also reduce nasopharyngeal carriage and can induce immune responses at the local
      mucosal level, which may be responsible for these effects. This article reviews
      recent studies on mucosal immune responses induced by polysaccharide based
      vaccines and some protein vaccine antigens against several pathogenic
      nasopharyngeal bacteria, and discusses the mechanisms and functions of these
      immune responses that may help our understanding of mucosal immune responses to
      both immunisation and infection.

PMID- 15452153
TI  - Cardiac troponins.

PMID- 15452154
TI  - Troponin I, laboratory issues, and clinical outcomes in a district general
      hospital: crossover study with "traditional" markers of myocardial infarction in
      a total of 1990 patients.
AB  - AIMS: Review of the clinical outcomes and practical issues of replacing
      traditional cardiac enzymes with troponin I (cTnI) in a district general
      hospital. METHODS: Crossover study of three sequential three month stages during
      which serial cardiac enzymes were replaced with a single cTnI measurement
      available at three set times within 24 hours for the duration of the second three
      month stage. The study was carried out in a 630 bed district general hospital
      with 1990 admissions of suspected cardiac ischaemia over the study period as a
      whole. Account was taken of seasonal factors. RESULTS: The introduction of
      troponin was associated with 8.5% more patients with non-ischaemic heart disease
      (IHD) being discharged on the day after admission, saving approximately 107 bed
      days each year. Approximately 50% more patients were diagnosed with myocardial
      infarction during the cTnI stage. There was no increase in readmission within one
      month or early death with cTnI. Approximately 3% false positive and 1.5% false
      negative cTnI results were recorded. All false positive cTnI results were coding
      errors or attributable to known assay interference effects. All false negatives
      were potentially explained by sample timing factors. The lack of standardisation
      in troponin assay services impacts clinically. CONCLUSION: Younger patients
      without IHD were discharged earlier during the cTnI stage in apparent safety.
      Blood sample timing needs to be verified when cTnI is used as an adjunct to early
      discharge. There were no unexplained false positives or negatives.
      Standardisation related issues arose.

PMID- 15452155
TI  - The prognostic value of progesterone receptor status in meningiomas.
AB  - BACKGROUND: Meningiomas are known to recur frequently, and their longterm
      management remains controversial. Previous studies indicate that progesterone and
      its receptors can play a role in the recurrence of meningiomas, but the
      correlation between the presence of these receptors and patients' outcome is
      unclear. AIM: To conduct a retrospective analysis to investigate the prognostic
      relevance of progesterone receptor (PR) expression in meningiomas. METHODS: Five
      hundred and eighty eight meningiomas operated on over a period of 10 years were
      examined immunohistochemically to determine the PR status using monoclonal
      antibodies. Several factors including recurrence (mean follow up of 65 month),
      sex, tumour tissue consistency, location, vascularity, and en plaque appearance
      were analysed. RESULTS: PR status showed comparable values for men and women.
      World Health Organisation (WHO) grade II and III tumours had significantly fewer
      receptors than benign meningiomas. There was no significant correlation between
      PR status and recurrence rates in WHO grade I totally removed meningiomas.
      However, a combination of PR status and proliferation indices was shown to
      predict recurrence reliably. CONCLUSIONS: Together with routine histological
      evaluation, PR status can help to describe the biological behaviour of
      meningiomas. Only a combination of clinical and biological features can describe
      the behaviour of meningiomas, predict their recurrence, and help to devise more
      effective follow up strategies.

PMID- 15452156
TI  - How should stainable iron in bone marrow films be assessed?
AB  - AIMS: To identify how many particles should be examined to enable a confident
      assessment of the presence or absence of iron stores and the quantity of iron in
      a bone marrow aspirate to be made. METHODS: One hundred and ninety consecutive
      bone marrow aspirate samples were stained with Perls' stain and the iron content
      of 10 consecutive particles was recorded. The first particle found to be positive
      and the particle that was most positive were also noted. RESULTS: A minimum of
      seven particles must be examined to establish the absence of stainable iron. A
      minimum of nine particles must be reviewed to see the maximum iron stores in 100%
      of samples and therefore make a valid judgment of whether iron stores are
      reduced, normal, or increased. By these criteria, 46% of the samples tested here
      could not be optimally assessed for absence of iron or maximum iron stores.
      CONCLUSIONS: The sensitivity of examination of bone marrow aspirates for iron
      stores can be optimised by increasing the number of particles reviewed to seven
      or more. This may require the staining of additional slides.

PMID- 15452157
TI  - Papillary carcinoma of the thyroid in Japan: subclassification of common type and
      identification of low risk group.
AB  - AIMS: Papillary thyroid carcinoma (PTC) is classified into two subgroups-common
      type and other histological variants. Correlations between further subgrouping of
      the common type and patient prognosis are not well documented. AIMS: To introduce
      two novel histological parameters to characterise PTC-loss of cellular polarity
      and loss of cellular cohesiveness. To investigate a new subgroup of common type
      PTC with possible prognostic value. METHODS: In total, 213 patients with PTCs
      larger than 1 cm were studied. Histological characteristics of these PTCs,
      including tumour growth pattern, encapsulation, extrathyroidal invasion, loss of
      cellular polarity, and loss of cellular cohesiveness were examined and correlated
      with disease free survival (DFS). RESULTS: Multivariate analysis revealed that
      invasive growth of unencapsulated PTC, in addition to sex (male) and tumour size
      (>4 cm) were significant and independent parameters for poor DFS, whereas loss of
      cellular polarity and cohesiveness, old age (>60 years), extrathyroid invasion,
      and completeness of surgery were significant only in univariate analysis. PTCs
      that showed expansive growth and retained cellular polarity had a favourable
      course, with no recurrence and no cancer related deaths. In contrast, PTCs
      exhibiting loss of cellular polarity and/or invasive growth with no tumour
      capsule had a higher risk of recurrence. CONCLUSION: Cytological features alone
      cannot predict patient outcome in PTC. This study indicates for the first time
      that loss of cellular polarity and the tumour growth pattern are useful
      parameters for identifying the so called low risk group in common type PTC and in
      predicting patient outcome in terms of tumour recurrence and cancer related
      death.

PMID- 15452158
TI  - Gastrin releasing peptide receptor expression is decreased in patients with
      Crohn's disease but not in ulcerative colitis.
AB  - BACKGROUND: Gastrin releasing peptide (GRP) and neuromedin B are bombesin (BN)
      like peptides involved in regulating motility and inflammation in the
      gastrointestinal tract, which may be useful in treating inflammatory bowel
      disease (IBD). Three bombesin-like peptide receptors have been reported, but no
      studies have investigated their localisation in normal and inflamed human
      intestine. AIM: To localise and characterise BN receptors in normal intestine and
      to see whether this is modified in IBD. METHODS: Full thickness intestinal tissue
      samples were collected from 13 patients with Crohn's disease (CD), 11 with
      ulcerative colitis (UC), and 19 controls. BN receptor expression was
      characterised and quantified with storage phosphor autoradiography using BN, GRP,
      neuromedin B, and the synthetic analogue BN(6-14) as ligands. RESULTS: Only BN
      receptor type 2 (high affinity for GRP) was present in intestinal tissue. Minimal
      BN binding was detected in the mucosa. In normal colonic smooth muscle, mean BN
      binding was 336 fmol/g tissue in longitudinal muscle, including the myenteric
      plexus, and 71 fmol/g in circular muscle. In CD, colonic smooth muscle BN binding
      was significantly decreased (longitudinal muscle, 106; circular muscle, 19
      fmol/g), in contrast to UC (377 and 62 fmol/g, respectively). In CD, a small (not
      significant) decrease was seen in ileal muscle compared with controls (111 v 169
      and 18 v 32 fmol/g tissue for longitudinal and circular muscle, respectively).
      CONCLUSIONS: Only the GRP receptor is expressed in human intestine; expression is
      highest in longitudinal muscle and myenteric plexus of the colon. Expression is
      decreased in inflamed and non-inflamed colon of CD, but not in UC.

PMID- 15452159
TI  - Spectrum of lymph node pathology in adult onset Still's disease; analysis of 12
      patients with one follow up biopsy.
AB  - BACKGROUND: Adult onset Still's disease (AOSD) is a rare systemic inflammatory
      disorder of unknown aetiology, frequently accompanying multiple lymphadenopathy.
      It often mimics malignant lymphoma, and immunohistochemical and molecular studies
      are needed for definite diagnosis. AIMS: To aid in diagnosis and understand the
      pathogenesis of the disease by clarifying lymph node (LN) pathology in AOSD.
      METHODS: Thirteen biopsies (one follow up biopsy) and medical records of 12
      patients were reviewed. Immunohistochemistry, polymerase chain reaction for T
      cell receptor gamma chain (TCRgamma) and immunoglobulin heavy chain gene
      rearrangement, and Epstein-Barr virus in situ hybridisation were performed.
      RESULTS: Histologically, LN lesions were classified into four patterns. The most
      common (six biopsies) showed paracortical hyperplasia, with prominent vascular
      proliferation, scattered large B/T immunoblasts, and infiltration by reactive
      lymphocytes and inflammatory cells. In the second pattern (two biopsies),
      paracortical hyperplasia was accompanied by massive sinus histiocytosis and S-100
      positive histiocyte aggregates. The third pattern (three patients) showed an
      exuberant immunoblastic reaction, in the form of patchy/diffuse infiltration of
      large T immunoblasts with high mitotic activity, although clonal rearrangement of
      the TCRgamma gene was not detected. The fourth pattern showed distinct follicular
      hyperplasia (two cases). One patient with a follow up biopsy showed a pattern
      change from pronounced follicular hyperplasia to atypical paracortical
      hyperplasia. CONCLUSIONS: AOSD LN lesions show a dynamic histological spectrum,
      including atypical paracortical hyperplasia, burnt out histiocytic reaction,
      exuberant immunoblastic reaction, and follicular hyperplasia. During the course
      of disease, LN reactivity changes and mixed B and T cells are involved in the
      pathogenesis.

PMID- 15452160
TI  - DNA replication regulation protein Mcm7 as a marker of proliferation in prostate
      cancer.
AB  - BACKGROUND: Recent studies have shown that minichromosome maintenance (MCM)
      proteins (Mcm2-7) may be useful proliferation markers in dysplasia and cancer in
      various tissues. AIMS: To investigate the use of Mcm7 as a proliferation marker
      in 79 lymph node negative prostate cancers and compare it with Ki-67, a commonly
      used cell proliferation marker. METHODS: The percentage of proliferating cells
      (proliferation index; PI) was calculated for basal and luminal epithelial cells
      in benign prostate tissue, prostatic intraepithelial neoplasia (PIN), and
      epithelial cells in adenocarcinoma. The PI for each biomarker was correlated with
      the preoperative prostate specific antigen concentration, the Gleason score,
      surgical resection margin status, and the AJCC pT stage for each patient.
      RESULTS: The mean PIs for Ki-67 and Mcm7 were: benign luminal epithelium 0.7 and
      1.2 and benign basal epithelium 0.8 and 8.2; PIN non-basal epithelium 4.9 and
      10.6 and PIN basal epithelium 0.7 and 3.1; adenocarcinoma 9.8 and 22.7,
      respectively. Mcm7 had a significantly higher mean PI (p<0.0001) than Ki-67 for
      all cell categories except benign luminal epithelial cells. Mcm7 was a better
      discriminatory marker of proliferation between benign epithelium, PIN, and
      invasive adenocarcinoma (p<0.0001) than Ki-67. The drop in Mcm7 mean basal cell
      PI from benign epithelium to PIN epithelium was significantly larger than for Ki
      67 (p<0.0001). Mcm7 had a significantly higher PI than Ki-67 at each risk level.
      CONCLUSION: Mcm7 may be a useful proliferation marker in prostatic neoplasia and
      warrants further evaluation as a complementary tool in the diagnosis of PIN and
      prostate carcinoma.

PMID- 15452161
TI  - The homeodomain protein CDX2 is an early marker of Barrett's oesophagus.
AB  - BACKGROUND: In Barrett's oesophagus (BO), squamous epithelium is replaced by
      specialised intestinal epithelium (SIE). Transcription factors associated with
      intestinal differentiation, such as CDX2, may be involved in BO development. AIM:
      To investigate CDX2 expression in BO, squamous epithelium, and oesophageal
      adenocarcinoma (ADC). METHODS: CDX2 expression was assessed in 245 samples-167
      biopsies of the columnar lined segment and 38 squamous epithelial biopsies of 39
      patients with histologically confirmed BO (10 with ADC). Forty biopsies from 20
      patients with reflux oesophagitis (RO) without BO were also evaluated. CDX2
      protein was investigated immunohistochemically in 138 biopsies from 16 patients
      with BO, four with ADC, and 20 with RO. Cdx2 and Muc2 mRNA were detected
      semiquantitatively using 88 BO biopsies and squamous epithelium from 19 BO
      patients, and when present from ADC. RESULTS: SIE was present in 53/79 biopsies
      from the columnar lined segment; CDX2 protein was seen in all epithelial cells,
      but not in biopsies containing only gastric metaplastic epithelium (26/79), or in
      squamous epithelium (0/40) of patients with RO. Cdx2 mRNA was detected in all
      biopsies with goblet cell specific Muc2 transcription-indicative of SIE. Low Cdx2
      mRNA expression was seen in 6/19 squamous epithelium samples taken 5 cm above the
      squamocolumnar junction of BO patients. CONCLUSION: CDX2 protein/mRNA is strongly
      associated with oesophageal SIE. Cdx2 mRNA was present in the normal appearing
      squamous epithelium of one third of BO patients, and may precede morphological
      changes seen in BO. Therefore, pathways that induce Cdx2 transcription in
      squamous epithelial cells may be important in BO development.

PMID- 15452162
TI  - Expression of SRC-1, AIB1, and PEA3 in HER2 mediated endocrine resistant breast
      cancer; a predictive role for SRC-1.
AB  - BACKGROUND: In human breast cancer, the growth factor receptor HER2 is associated
      with disease progression and resistance to endocrine treatment. Growth factor
      induced mitogen activated protein kinase activity can phosphorylate not only the
      oestrogen receptor, but also its coactivator proteins AIB1 and SRC-1. AIM: To
      determine whether insensitivity to endocrine treatment in HER2 positive patients
      is associated with enhanced expression of coactivator proteins, expression of the
      HER2 transcriptional regulator, PEA3, and coregulatory proteins, AIB1 and SRC-1,
      was assessed in a cohort of patients with breast cancer of known HER2 status.
      METHODS: PEA3, AIB1, and SRC-1 protein expression in 70 primary breast tumours of
      known HER2 status (HER2 positive, n = 35) and six reduction mammoplasties was
      assessed using immunohistochemistry. Colocalisation of PEA3 with AIB1 and SRC-1
      was determined using immunofluorescence. Expression of PEA3, AIB1, and SRC-1 was
      correlated with clinicopathological parameters. RESULTS: In primary breast
      tumours expression of PEA3, AIB1, and SRC-1 was associated with HER2 status (p =
      0.0486, p = 0.0444, and p = 0.0012, respectively). In the HER2 positive
      population, PEA3 expression was associated with SRC-1 (p = 0.0354), and both PEA3
      and SRC-1 were significantly associated with recurrence on univariate analysis (p
      = 0.0345; p<0.0001). On multivariate analysis, SRC-1 was significantly associated
      with disease recurrence in HER2 positive patients (p = 0.0066). CONCLUSION:
      Patients with high expression of HER2 in combination with SRC-1 have a greater
      probability of recurrence on endocrine treatment compared with those who are HER2
      positive but SRC-1 negative. SRC-1 may be an important predictive indicator and
      therapeutic target in breast cancer.

PMID- 15452163
TI  - c-KIT and PDGFRA in breast phyllodes tumours: overexpression without mutations?
AB  - AIM: To study the immunoexpression and mutational status of c-KIT and PDGFRA in a
      series of benign and malignant phyllodes tumours of the breast. MATERIAL/METHODS:
      Nineteen phyllodes tumours (13 benign and six malignant) were analysed by
      immunohistochemistry for the expression of c-KIT and PDGFRA. Direct sequencing of
      exons 9, 11, 13, and 17 of the c-KIT gene and exons 12 and 18 of PDGFRA was
      performed to check the mutational status of these two genes. RESULTS: c-KIT
      expression was found in 12 of the 19 cases (six of the 13 benign cases and all
      six malignant ones) and PDGFRA expression was seen in two of the 19 cases (one
      benign and one malignant case); the 2415 C>T alteration in exon 17 of the c-KIT
      gene was found in two cases (both benign); the intronic insertion IVS17-50insT
      and the 2866 G>T alteration in the coding region of exon 18 of the PDGFRA gene
      were also found in two cases (one malignant and one benign). However, the
      activating mutations described for these genes in gastrointestinal stromal
      tumours were not present. CONCLUSION: c-KIT expression is a frequent finding in
      phyllodes tumours, particularly in malignant cases; however, no activating
      mutations similar to those described for gastrointestinal stromal tumours were
      found. The PDGFRA does not seem to be an alternative pathway to tumour
      development in phyllodes tumours because neither expression nor activating
      mutations were noteworthy.

PMID- 15452164
TI  - Expression of mismatch repair proteins, beta catenin, and E cadherin in
      intestinal-type sinonasal adenocarcinoma.
AB  - BACKGROUND: Despite their histological resemblance to colorectal adenocarcinomas,
      there is little information about the molecular events involved in the
      pathogenesis of intestinal-type sinonasal adenocarcinomas (ITACs). AIMS: To
      evaluate the possible role of DNA mismatch repair (MMR) gene defects or
      disruptions of the E cadherin-beta catenin complex in ITAC by investigating the
      immunohistochemical expression of the MMR gene products, beta catenin, and E
      cadherin in a group of sporadic ITACs. METHODS: Ten sporadic cases of ITAC were
      stained with antibodies against MLH1, MSH2, MSH3, MSH6, beta catenin, and E
      cadherin. RESULTS: Nine cases showed strong nuclear expression of MLH1, whereas
      one case showed moderate staining. All 10 cases were strongly positive for MSH2
      and MSH3. MSH6 was strong in nine cases, and moderate in one. Membranous beta
      catenin expression was strong in all 10 cases, and no case showed cytoplasmic or
      nuclear staining. E cadherin was strong in seven cases, and moderate in three
      cases. CONCLUSIONS: The preserved nuclear expression of MLH1, MSH2, MSH3, and
      MSH6 suggests that mutations or promoter methylation of MMR genes do not play a
      role in the pathogenesis of ITAC. The strong membranous staining for E cadherin
      and beta catenin and lack of abnormal cytoplasmic or nuclear expression is in
      keeping with the preservation of E cadherin-beta catenin complexes and beta
      catenin pathways.

PMID- 15452165
TI  - Comparative molecular pathology of sporadic hyperplastic polyps and neoplastic
      lesions from the same individual.
AB  - AIM: The biology of colorectal hyperplastic polyps is of considerable relevance,
      because recent evidence suggests that under certain circumstances hyperplastic
      polyps may be precursors of neoplasms. The aim of this study was to assess and
      compare the clinical and molecular characteristics of hyperplastic polyps and
      neoplastic lesions removed from patients without the hyperplastic polyposis
      syndrome. METHODS: One hundred and twenty six patients were identified through a
      series of genetic epidemiological studies. Each patient had at least one
      neoplastic lesion and one hyperplastic polyp; there was a total of 147
      hyperplastic polyps. All lesions were evaluated for K-ras mutations, loss of
      heterozygosity (LOH) of the adenomatous polyposis coli (APC) gene, and
      microsatellite instability. RESULTS: K-ras mutation was detected in 15 (10%)
      hyperplastic polyps, all from the rectosigmoid colon. No hyperplastic polyp had
      APC LOH or microsatellite instability. Patients with adenomas or carcinomas
      showing K-ras mutations were not more likely to have hyperplastic polyps with K
      ras mutations. The average number of adenomas did not differ between those
      patients with hyperplastic polyps with K-ras mutations and those without K-ras
      mutations. There was no association between the hyperplastic polyp and the
      adenoma regarding the colon segments from which the two lesions were removed.
      CONCLUSIONS: The sporadic hyperplastic polyp is a lesion with limited molecular
      change and no relation to patients' neoplastic lesions.

PMID- 15452166
TI  - Proximal versus distal hyperplastic polyps of the colorectum: different lesions
      or a biological spectrum?
AB  - BACKGROUND: Because of their suggested link with microsatellite instability high
      colorectal cancers, right sided hyperplastic polyps (HPs) may differ from their
      distally located counterparts. This is highlighted by the recognition of a
      variant HP, termed sessile serrated adenoma (SSA), which predominates in the
      proximal colon. HPs displaying the morphological features now associated with
      SSAs have been shown to have altered expression of "cancer associated" markers,
      but no studies have investigated whether this is dependent on anatomical location
      of the polyps. AIMS: To evaluate morphological and functional features in right
      versus left sided HPs from patients without colorectal cancer with the aim of
      identifying distinguishing characteristics. METHODS: HPs originating in the
      proximal and distal colorectum were histochemically and immunohistochemically
      stained to evaluate a panel of markers related to proliferation and
      differentiation. In addition, a series of morphological features was evaluated
      for each polyp. RESULTS: Crypt serration, crypt dilatation, and horizontal crypt
      growth were more common among HPs from the right side, whereas histochemical
      factors including mucin changes, global methylation status, and expression of
      carcinoembryonic antigen were not significantly different. An age disparity was
      also seen between patients with right versus left sided lesions, with patients
      with right sided lesions being an average of more than 10 years younger than
      those with left sided lesions. CONCLUSIONS: These findings suggest that right and
      left sided HPs differ mainly in terms of growth regulation rather than cellular
      differentiation, implying that these lesions belong to a continuous spectrum of
      serrated polyps that differ quantitatively rather than qualitatively.

PMID- 15452167
TI  - Haptoglobin genotypic distribution (including Hp0 allele) and associated serum
      haptoglobin concentrations in Koreans.
AB  - BACKGROUND: Haptoglobin polymorphism is associated with the prevalence of
      infections, autoimmune diseases, cardiovascular diseases, and other disorders.
      Congenital haptoglobin deficiency is associated with anaphylactic transfusion
      reactions in anhaptoglobinaemic patients with antihaptoglobin antibody. AIMS: To
      investigate haptoglobin genotypic distribution (including the Hp(0) allele) and
      associated serum haptoglobin concentrations in Koreans. METHODS: Five hundred and
      nine healthy Korean adults were randomly selected. Two methods were used:
      haptoglobin genotyping based on a polymerase chain reaction (PCR) system that
      exploited the structural difference of the Hp(1) and Hp(2 )alleles, and another
      PCR method that detected haptoglobin gene deletion by amplification of the
      junctional region of the Hp(0) allele. Serum haptoglobin concentrations were
      measured by nephelometry. RESULTS: The haptoglobin genotypes of 509 subjects were
      as follows: Hp(1)Hp(1), 7.1%; Hp(2)Hp(1), 37.7%; Hp(2)Hp(2), 49.3%; Hp(0)Hp(1),
      2.2%; Hp(0)Hp(2), 3.5%; Hp(0)Hp(0), 0.2%. The gene frequency of Hp(0) in Koreans
      was calculated to be 0.031. Significant differences were seen among the
      concentrations of each haptoglobin genotype (Kruskal-Wallis test). Hp(0)Hp(2),
      but not Hp(0)Hp(1), was associated with hypohaptoglobinaemia. CONCLUSIONS: PCR
      methods for differentiating between haptoglobin genotypes, including the Hp(0)
      allele, may be useful in a broad spectrum of basic studies and clinical
      examinations.

PMID- 15452168
TI  - Spurious rise in the automated platelet count because of bacteria.
AB  - The era of automation in haematology, although improving the accuracy and
      precision of results, has also introduced the laboratory haematologist to a vast
      array of spurious parameters. The identification of these results is important so
      that inappropriate management decisions are avoided. The case presented here
      illustrates a spuriously raised automated platelet count resulting from bacterial
      overgrowth in the blood sample.

PMID- 15452169
TI  - Large cell neuroendocrine carcinoma of the ampulla of Vater with glandular
      differentiation.
AB  - Large cell neuroendocrine carcinoma of the ampulla of Vater is extremely rare. A
      55 year old woman presented with an ampullary tumour causing pancreaticobiliary
      obstruction and a pancreaticoduodenectomy was performed. Microscopically, the
      tumour was diagnosed as a CD117 positive large cell neuroendocrine carcinoma with
      glandular differentiation. Four months later the patient developed a general
      recurrence. The metastatic tumours showed CD117 negativity and pure
      neuroendocrine features. The patient died of disease six months after diagnosis.
      It is postulated that the two components originated from a common multipotential
      stem cell. The clinical behaviour of ampullary large cell neuroendocrine
      carcinomas appears to be highly aggressive, with early metastases and a fatal
      outcome.

PMID- 15452170
TI  - Fatal renal failure as the first manifestation of sarcoidosis diagnosed on
      necropsy in a young man: a case report.
AB  - Renal involvement as the first manifestation of sarcoidosis is rare and has never
      been reported in India. This report describes a 35 year old man who was admitted
      to the emergency department with a clinical diagnosis of acute on chronic renal
      failure, secondary to obstructive uropathy. Postmortem examination unexpectedly
      revealed disseminated sarcoidosis.

PMID- 15452171
TI  - Endometrial coccidiosis.
AB  - This report describes a case of granulomatous endometritis caused by coccidiosis
      in an immunologically uncompromised 63 year old patient. The glandular epithelium
      of the endometrium contained numerous intracytoplasmic cysts, corresponding to
      periodic acid Schiff positive and methenamine silver negative sporoblasts. The
      endometrial glands revealed reactive phenomena, such as eosinophilic and squamous
      glandular metaplasia and intraluminal desquamation. Non-necrotising epithelioid
      granulomata, lacking the presence of parasites, were present in the stroma.
      Although not detected in the stool examination, the organisms were probably
      Isospora belli. There was no evidence of other foci of the disease. Coccidiosis
      should be differentiated from the more commonly occurring coccidiomycosis.

PMID- 15452172
TI  - Pancreatic endocrine tumour with cytoplasmic keratin whorls. Is the term
      "rhabdoid" appropriate?
AB  - A 50 year old woman presented with acute abdominal pain accompanied by nausea and
      vomiting and was found to have a mass in the head of the pancreas by imaging. The
      clinical impression was of a pancreatic carcinoma and a Whipple's procedure was
      performed. Microscopic examination of the tumour showed it to be a low grade
      neuroendocrine carcinoma arranged in a tubuloacinar or tubulopapillary pattern,
      and composed of cells harbouring very prominent intracytoplasmic inclusions.
      These inclusions varied in appearance from being pale pink and hyaline in quality
      to more eosinophilic and globular causing displacement of the nucleus.
      Ultrastructural examination showed typical paranuclear aggregates of intermediate
      filaments. Inclusions of this type have been described previously as "signet ring
      like" and "rhabdoid". It was felt that the inclusions more closely resemble the
      fibrous bodies that are seen in pituitary adenomas. In addition, it is suggested
      that both signet ring and rhabdoid are not appropriate because they do not
      reflect histogenesis and are not necessarily reflective of tumour biology. It is
      suggested that the term "cytokeratin aggresomes" should be used to describe this
      distinctive phenotype.

PMID- 15452173
TI  - Expression of thyroid transcription factor 1 in primary brain tumours.
AB  - BACKGROUND: Thyroid transcription factor 1 (TTF-1) is expressed in a proportion
      of carcinomas derived from follicular thyroid cells and respiratory epithelium.
      Immunohistochemical detection of this protein was shown previously to be a
      helpful aid in tumour diagnosis, specifically in deciding whether a tumour is
      primary to the lung/thyroid gland or metastatic. Recently, TTF-1 expression was
      also observed in certain areas of postnatal brain. AIM/METHOD: To investigate the
      expression of TTF-1 protein in a spectrum of 73 primary brain tumours including
      astrocytomas, glioblastomas, ependymomas, oligodendrogliomas, medulloblastomas,
      and gangliogliomas of different sites. RESULTS: All the tumours were negative for
      TTF-1 except for two ependymomas of the third ventricle. CONCLUSIONS: The
      expression of TTF-1 in brain tumours appears to be site specific rather than
      associated with tumour dedifferentiation. The presented expression of TTF-1
      protein in certain primary brain tumours should be taken into consideration when
      interpreting the immunohistochemical staining of brain tumours of uncertain
      primary site.

PMID- 15452174
TI  - Reversal of glandular polarity in the lymphovascular compartment of breast
      cancer.
AB  - AIM: To investigate the polarity of breast invasive ductal carcinoma cells by
      comparing the polarity of the tumour located within lymphovascular spaces with
      that located in the extravascular compartment. METHODS: An immunohistochemical
      study identifying the apical HMFG-1, basolateral AUA-1, and basal laminin
      polarity markers of 11 cases of invasive ductal carcinoma (grades 1 or 2)
      metastatic to lymph nodes, all of which contained areas of tumour within and
      outside of lymphovascular spaces. RESULTS: Only one of 11 tumours had a focus of
      apparent reversed glandular polarity in the larger extravascular tumour
      compartment (with AUA-1 present internally and HMFG-1 expressed externally on
      tumour clumps), but six of the 11 tumours showed reversed glandular polarity
      (either with AUA-1, or HMFG-1, or both) within the very much smaller
      lymphovascular space tumour compartment. Laminin was not identified in
      association with lymphovascular tumour. CONCLUSIONS: Reversed glandular polarity
      in invasive ductal breast carcinomas was identified and was significantly more
      frequent within vessels than outside of them. Reversal of tumour glandular
      polarity within lymphovascular spaces allows direct interaction between apical
      domain-type molecules-which are then aberrantly expressed on the external surface
      of tumour clumps-and lymphovascular endothelium. Such interactions may affect the
      establishment of metastatic disease.

PMID- 15452175
TI  - Adenocarcinoma arising in villous adenoma of the ampulla of Vater with
      synchronous malignant gastrointestinal stromal tumour of the duodenum: a case
      report.

PMID- 15452176
TI  - Intra-abdominal fibromatosis of the jejunum and mesentery.

PMID- 15452177
TI  - Coordinate expression and trans presentation of interleukin (IL)-15Ralpha and IL
      15 supports natural killer cell and memory CD8+ T cell homeostasis.
AB  - The high affinity interleukin (IL)-15 receptor, IL-15Ralpha, is essential for
      supporting lymphoid homeostasis. To assess whether IL-15Ralpha's role in vivo is
      to trans present IL-15, we generated mixed bone marrow chimera from IL-15Ralpha-
      and IL-2/15Rbeta-deficient mice. We find that IL-15Ralpha-competent, IL-2/15Rbeta
      deficient cells are able to support IL-15Ralpha-deficient natural killer (NK) and
      memory CD8+ T cells, thus ruling out secondary signals on these cells and
      demonstrating that IL-15Ralpha-mediated presentation of IL-15 in trans is the
      primary mechanism by which IL-15Ralpha functions in vivo. Surprisingly, using IL
      15- and IL-15Ralpha-deficient mixed chimera, we also find that IL-15 and IL
      15Ralpha must be expressed by the same cells to present IL-15 in trans,
      indicating that IL-15Ralpha is required on a cellular level for the elaboration
      of IL-15. These studies indicate that IL-15Ralpha defines homeostatic niches for
      NK and memory CD8+ T cells by controlling both the production and the
      presentation of IL-15 in trans to NK and CD8+ memory T cells.

PMID- 15452178
TI  - Varicella-zoster virus transfer to skin by T Cells and modulation of viral
      replication by epidermal cell interferon-alpha.
AB  - Primary infection with varicella-zoster virus (VZV) causes the characteristic
      syndrome of varicella, or chickenpox. Experiments in severe combined
      immunodeficiency mice with human skin grafts (SCIDhu mice) indicate that VZV
      infection of T cells can mediate transfer of infectious virus to skin. VZV
      infected T cells reached epithelial sites of replication within 24 h after
      entering the circulation. Memory CD4+ T cells were the predominant population
      recovered from skin in SCIDhu mice given uninfected or infected mononuclear
      cells, suggesting that immune surveillance by memory T cells may facilitate VZV
      transfer. The increased susceptibility of memory T cells to VZV infection may
      further enhance their role in VZV pathogenesis. During VZV skin infection, viral
      gene products down-regulated interferon-alpha to permit focal replication,
      whereas adjacent epidermal cells mounted a potent interferon-alpha response
      against cell-cell spread. Interleukin-1alpha, although activated in VZV-infected
      cells, did not trigger expression of endothelial adhesion molecules, thereby
      avoiding early recruitment of inflammatory cells. The prolonged varicella
      incubation period appears to represent the time required for VZV to overcome
      antiviral responses of epidermal cells and generate vesicles at the skin surface.
      Modulation of VZV replication by cutaneous innate immunity may avoid an
      incapacitating infection of the host that would limit opportunities for VZV
      transmission.

PMID- 15452179
TI  - RANKL-induced DC-STAMP is essential for osteoclastogenesis.
AB  - Osteoclasts are bone-resorbing, multinucleated giant cells that are essential for
      bone remodeling and are formed through cell fusion of mononuclear precursor
      cells. Although receptor activator of nuclear factor-kappaB ligand (RANKL) has
      been demonstrated to be an important osteoclastogenic cytokine, the cell surface
      molecules involved in osteoclastogenesis are mostly unknown. Here, we report that
      the seven-transmembrane receptor-like molecule, dendritic cell-specific
      transmembrane protein (DC-STAMP) is involved in osteoclastogenesis. Expression of
      DC-STAMP is rapidly induced in osteoclast precursor cells by RANKL and other
      osteoclastogenic stimulations. Targeted inhibition of DC-STAMP by small
      interfering RNAs and specific antibody markedly suppressed the formation of
      multinucleated osteoclast-like cells. Overexpression of DC-STAMP enhanced
      osteoclastogenesis in the presence of RANKL. Furthermore, DC-STAMP directly
      induced the expression of the osteoclast marker tartrate-resistant acid
      phosphatase. These data demonstrate for the first time that DC-STAMP has an
      essential role in osteoclastogenesis.

PMID- 15452180
TI  - The loss of PTEN allows TCR alphabeta lineage thymocytes to bypass IL-7 and Pre
      TCR-mediated signaling.
AB  - The phosphatase and tensin homologue deleted on chromosome 10 (PTEN) negatively
      regulates cell survival and proliferation mediated by phosphoinositol 3 kinases.
      We have explored the role of the phosphoinositol(3,4,5)P3-phosphatase PTEN in T
      cell development by analyzing mice with a T cell-specific deletion of PTEN.
      Pten(flox/flox)Lck-Cre mice developed thymic lymphomas, but before the onset of
      tumors, they showed normal thymic cellularity. To reveal a regulatory role of
      PTEN in proliferation of developing T cells we have crossed PTEN-deficient mice
      with mice deficient for interleukin (IL)-7 receptor and pre-T cell receptor (TCR)
      signaling. Analysis of mice deficient for Pten and CD3gamma; Pten and gammac; or
      Pten, gammac, and Rag2 revealed that deletion of PTEN can substitute for both IL
      7 and pre-TCR signals. These double- and triple-deficient mice all develop normal
      levels of CD4CD8 double negative and double positive thymocytes. These data
      indicate that PTEN is an important regulator of proliferation of developing T
      cells in the thymus.

PMID- 15452181
TI  - Chlamydia inhibit host cell apoptosis by degradation of proapoptotic BH3-only
      proteins.
AB  - Chlamydia are obligate intracellular bacteria that replicate in a vacuole inside
      a host cell. Chlamydial infection has been shown to protect the host cell against
      apoptotic stimuli. This is likely important for the ability of Chlamydia to
      reproduce in human cells. Here we show that resistance to apoptosis is conveyed
      by the destruction of the proapoptotic BH3-only proteins Bim/Bod, Puma, and Bad
      during infection. Apoptotic stimuli were blocked upstream of the mitochondrial
      activation of Bax/Bak. During infection with both species, Chlamydia trachomatis
      and Chlamydia pneumoniae, Bim protein gradually disappeared without noticeable
      changes in Bim mRNA. The disappearance was blocked by inhibitors of the
      proteasome. Infected cells retained sensitivity to Bim expressed by transfection,
      indicating functional relevance of the Bim disappearance. Fusion to Bim targeted
      the green fluorescent protein for destruction during infection. Analysis of
      truncation mutants showed that a short region of Bim containing the BH3 domain
      was sufficient for destruction during chlamydial infection. Like Bim, Puma and
      Bad proteins disappeared during infection. These results reveal a novel way by
      which microbes can interfere with the host cell's apoptotic machinery, and
      provide a molecular explanation of the cellular resistance to apoptosis during
      infection with Chlamydia.

PMID- 15452182
TI  - Patterns of locoregional failure in patients with operable breast cancer treated
      by mastectomy and adjuvant chemotherapy with or without tamoxifen and without
      radiotherapy: results from five National Surgical Adjuvant Breast and Bowel
      Project randomized clinical trials.
AB  - PURPOSE: To assess patterns of locoregional failure (LRF) in lymph node-positive
      (LN+) breast cancer patients treated with mastectomy and adjuvant chemotherapy
      (+/- tamoxifen) and without postmastectomy radiotherapy (PMRT) in five National
      Surgical Adjuvant Breast and Bowel Project trials. PATIENTS AND METHODS: We
      examined 5,758 patients enrolled onto the B-15, B-16, B-18, B-22, and B-25
      trials. Median follow-up time was 11.1 years. Distribution of pathologic tumor
      size was < or = 2 cm, 2.1 to 5 cm, and more than 5 cm in 30%, 52%, and 11% of
      patients, respectively. Distribution of the number of LN+ was one to three, four
      to nine, and > or = 10 in 51%, 32%, and 16% of patients, respectively. Ninety
      percent of patients received doxorubicin-based chemotherapy. RESULTS: The overall
      10-year cumulative incidences of isolated LRF, LRF with or without distant
      failure (DF), and DF alone as first event were 12.2%, 19.8%, and 43.3%,
      respectively. Cumulative incidences for LRF as first event with or without DF for
      patients with one to three, four to nine, and > or = 10 LN+ were 13.0%, 24.4%,
      and 31.9%, respectively (P < .0001). For patients with a tumor size of < or = 2
      cm, 2.1 to 5.0 cm, and more than 5.0 cm, these incidences were 14.9%, 21.3%, and
      24.6%, respectively (P < .0001). Multivariate analysis showed age, tumor size,
      premenopausal status, number of LN+, and number of dissected LN as significant
      predictors for LRF as first event. CONCLUSION: In patients with large tumors and
      four or more LN+, LRF as first event remains a significant problem. Although PMRT
      is currently recommended for patients with four or more LN+, it may also have
      value in selected patients with one to three LN+. However, in the absence of a
      randomized trial examining the worth of radiotherapy in this group of patients,
      the value of PMRT remains unknown.

PMID- 15452183
TI  - Support groups in breast cancer: when a negative result is positive.

PMID- 15452184
TI  - Toward a glioblastoma vaccine: promise and potential pitfalls.

PMID- 15452185
TI  - Postmastectomy radiation therapy: who needs it?

PMID- 15452186
TI  - Antitumor vaccination of patients with glioblastoma multiforme: a pilot study to
      assess feasibility, safety, and clinical benefit.
AB  - PURPOSE: Prognosis of patients with glioblastoma is poor. Therefore, in
      glioblastoma patients, we analyzed whether antitumor vaccination with a virus
      modified autologous tumor cell vaccine is feasible and safe. Also, we determined
      the influence on progression-free survival and overall survival and on
      vaccination-induced antitumor reactivity. PATIENTS AND METHODS: In a
      nonrandomized study, 23 patients were vaccinated and compared with nonvaccinated
      controls (n = 87). Vaccine was prepared from patient's tumor cell cultures by
      infection of the cells with Newcastle Disease Virus, followed by gamma
      irradiation, and applied up to eight times. Antitumor immune reactivity was
      determined in skin, blood, and relapsed tumor by delayed-type hypersensitivity
      skin reaction, ELISPOT assay, and immunohistochemistry, respectively. RESULTS:
      Establishment of tumor cell cultures was successful in approximately 90% of
      patients. After vaccination, we observed no severe side effects. The median
      progression-free survival of vaccinated patients was 40 weeks (v 26 weeks in
      controls; log-rank test, P = .024), and the median overall survival of vaccinated
      patients was 100 weeks (v 49 weeks in controls; log-rank test, P < .001). Forty
      five percent of the controls survived 1 year, 11% survived 2 years, and there
      were no long-term survivors (> or = 3 years). Ninety-one percent of vaccinated
      patients survived 1 year, 39% survived 2 years, and 4% were long-term survivors.
      In the vaccinated group, immune monitoring revealed significant increases of
      delayed-type hypersensitivity reactivity, numbers of tumor-reactive memory T
      cells, and numbers of CD8(+) tumor-infiltrating T-lymphocytes in secondary
      tumors. CONCLUSION: Postoperative vaccination with virus-modified autologous
      tumor cells seems to be feasible and safe and to improve the prognosis of
      patients with glioblastomas. This could be substantiated by the observed
      antitumor immune response.

PMID- 15452187
TI  - Phase III, randomized, double-blind study of epoetin alfa compared with placebo
      in anemic patients receiving chemotherapy.
AB  - PURPOSE: To determine whether weekly epoetin alfa could improve hemoglobin (HgB)
      levels, reduce RBC transfusions, and improve quality of life (QOL) in patients
      with advanced cancer and with anemia after receiving myelosuppressive
      chemotherapy. PATIENTS AND METHODS: This double-blind, placebo-controlled study
      randomly assigned patients to placebo or epoetin alfa (Ortho Biotech,
      Bridgewater, NJ) 40,000 U subcutaneous weekly for 16 weeks. QOL, HgB, and RBC
      transfusions were measured pretreatment and monthly. RESULTS: The study accrued
      344 patients; 330 were assessable for efficacy and 305 were assessable for QOL.
      Placebo-treated patients had a mean increase in HgB of 0.9 g/dL (range, -3.8 to
      +5.3) compared with 2.8 g/dL (range, -2.2 to +7.5) for epoetin-treated patients
      (P < .0001). During the study, 31.7% of placebo-treated patients achieved a > or
      = 2 g/dL HgB increase compared with 72.7% of epoetin-treated patients (P <
      .0001). The incidence of RBC transfusion for placebo and epoetin treatment arms
      was 39.6% and 25.3% (P = .005), respectively. The placebo group received 256
      units of RBCs compared with 127 units in the epoetin group (P < .0001). The
      incidence of toxicity in the groups was similar. Changes in the average QOL
      scores from baseline to the end of the study were similar in the two groups (P =
      not significant). The HgB responders (irrespective of treatment arm) had a mean
      change in Functional Assessment of Cancer Therapy (FACT) fatigue score from a
      baseline of +5.1 compared with -2.1 for the nonresponders (P = .006). CONCLUSION:
      Epoetin alfa significantly improved HgB and reduced transfusions in this patient
      population. These results support the use of weekly epoetin alfa as an
      ameliorative agent for cancer-related anemia.

PMID- 15452188
TI  - Weekly epoetin alfa maintains hemoglobin, improves quality of life, and reduces
      transfusion in breast cancer patients receiving chemotherapy.
AB  - PURPOSE: Epoetin alfa administered at 40,000 U once weekly (qw) to anemic cancer
      patients receiving chemotherapy increases hemoglobin levels, improves quality of
      life (QOL), and reduces transfusions. The benefit of epoetin alfa in maintaining
      hemoglobin levels in cancer patients with hemoglobin less than 12 g/dL has not
      been evaluated. METHODS: Breast cancer patients (N = 354) receiving chemotherapy
      were randomly assigned in 1:1 ratio to epoetin alfa (40,000 U qw) or standard of
      care (SOC). QOL was assessed at baseline and week 12. Hemoglobin responses,
      transfusion requirements, and prognostic factors for responses were measured.
      RESULTS: At week 12, Functional Assessment of Cancer Therapy-Anemia (FACT-An;
      mean, 2.16 +/- 12.84 for epoetin alfa v -4.43 +/- 13.42 for SOC) and FACT-An
      fatigue (mean, 1.85 +/- 10.52 for epoetin alfa v -3.55 +/- 11.14 for SOC) change
      scores were significantly higher in the epoetin alfa group (P < .0001).
      Hemoglobin responses defined as mean hemoglobin > or = 12 g/dL or a > or = 2 g/dL
      increase compared with baseline were significantly higher in the epoetin alfa
      group versus SOC: 52.0% v 5.1% and 65.7% v 6.3%, respectively (P < .0001 for both
      comparisons). Percentage transfused was significantly lower in the epoetin alfa
      group compared with SOC (8.6% v 22.9%). More than 90% of patients did not require
      a dose increase and 28.7% had a dose reduction. CONCLUSION: Epoetin alfa
      administered at 40,000 U qw is effective in improving QOL, maintaining hemoglobin
      level, and reducing transfusion requirements in breast cancer patients. The high
      effectiveness observed could be attributed in part to early treatment with
      epoetin alfa.

PMID- 15452189
TI  - Effect of cognitive-existential group therapy on survival in early-stage breast
      cancer.
AB  - PURPOSE: Cognitive-existential group therapy (CEGT) was developed to improve mood
      and mental attitude toward cancer in women with early-stage breast cancer
      receiving adjuvant chemotherapy. Given the debate about group therapy's
      association with increased survival in women with metastatic breast cancer, we
      were curious to check its effect at a much earlier stage in the cancer journey.
      PATIENTS AND METHODS: We randomly assigned 303 women with early-stage breast
      cancer who were receiving adjuvant chemotherapy to either 20 sessions of weekly
      group therapy plus three relaxation classes (n = 154) or to a control condition
      of three relaxation classes alone (n = 149). The primary outcome was survival.
      RESULTS: CEGT did not extend survival; the median survival time was 81.9 months
      (95% CI, 64.8 to 99.0 months) in the group-therapy women and 85.5 months (95% CI,
      67.5 to 103.6 months) in the control arm. The hazard ratio for death was 1.35
      (95% CI, 0.76 to 2.39; P = .31). In contrast, histology and axillary lymph node
      status were significant predictors of survival. Low-grade histology yielded a
      hazard ratio of 0.342 (95% CI, 0.17 to 0.69), and axillary lymph node-negative
      status yielded a hazard ratio of 0.397 (95% CI, 0.20 to 0.78). CONCLUSION: CEGT
      does not prolong survival in women with early-stage breast cancer.

PMID- 15452190
TI  - Hemodynamic effects of phosphodiesterase 5 and angiotensin-converting enzyme
      inhibition alone or in combination in conscious SHR.
AB  - The regional hemodynamic responses to continuous 4-day infusion of UK-357,903 [1
      ethyl-4-{3-[3-ethyl-6,7-dihydro-7-oxo-2-(2-pyridylmethyl)-2H-pyrazolo[4,3
      d]pyrimidin-5-yl]-2-(2-methoxyethoxy)-5-pyridylsulphonyl}piperazine] (266 microg
      kg(-1) h(-1)) alone and in combination with a low dose of enalapril (10 microg
      kg(-1) h(-1)) were measured in conscious spontaneously hypertensive rats to test
      the hypothesis that the renin-angiotensin system may influence the cardiovascular
      consequences of inhibition of phosphodiesterase 5 (PDE5) by UK-357,903 or vice
      versa. UK-357,903 alone caused a fall in mean blood pressure (-12.1 mm Hg)
      associated with vasodilatation in the mesenteric and hindquarters vascular beds.
      The only way in which the effects of enalapril given alone differed significantly
      from those of the vehicle was in causing mesenteric vasodilatation, which
      developed over the 4 days of infusion. UK-357,903 given in combination with
      enalapril caused hypotension (-17.8 mm Hg) and vasodilatation in the renal,
      mesenteric, and hindquarter vascular beds. There was evidence of a significant
      interaction between the effects of the two compounds on renal Doppler shift and
      vascular conductance with the combined action of the two compounds being greater
      than the sum of their individual effects. However, although there was a trend for
      the combination to have greater effects than either of the individual agents on
      blood pressure and mesenteric vascular conductance, there was no statistical
      evidence of an interaction. The results indicate that inhibition of the renin
      angiotensin system uncovers additional renal vasodilator effects of UK-357,903,
      and/or inhibition of PDE5 enhances the renal vasodilator effects of angiotensin
      converting enzyme inhibition.

PMID- 15452191
TI  - Inhibition of phenylephrine-induced cardiomyocyte hypertrophy by activation of
      multiple adenosine receptor subtypes.
AB  - Plasma adenosine levels are elevated in cardiovascular disease including
      hypertension and heart failure, and the nucleoside has been proposed to serve as
      an endogenous antimyocardial remodeling factor. We studied the modulation of
      phenylephrine-induced hypertrophy by adenosine receptor activation in isolated
      neonatal cultured ventricular myocytes. Phenylephrine (10 muM) increased cell
      size by 35% and significantly increased expression of atrial natriuretic peptide.
      These effects were reduced by the stable adenosine analog 2-chloroadenosine and
      were completely blocked by the adenosine A(1) receptor agonist N(6)
      cyclopentyladenosine (1 microM), the A(2A) receptor agonist 2-p-(2-carboxyethyl)
      phenethylamino-5'-N-ethylcarboxamidoadenosine (100 nM), and the A(3) receptor
      agonist N(6)-(3-iodobenzyl)adenosine-5'-methyluronamide (100 nM). The
      antihypertrophic effects of all three agonists were completely reversed by their
      respective antagonists. Phenylephrine significantly up-regulated expression of
      the immediate early gene c-fos especially within the first 30 min of
      phenylephrine treatment. These effects were almost completely inhibited by all
      adenosine receptor agonists. Although phenylephrine also induced early
      stimulation of both p38 mitogen-activated protein kinase and extracellular signal
      regulated kinase, these responses were unaffected by adenosine agonists. The
      expression of the G-protein regulatory factors RGS2 and RGS4 were increased by
      nearly 3-fold by phenylephrine treatment although this was completely prevented
      by adenosine receptor agonists. These agents also blocked the ability of
      phenylephrine to up-regulate Na/H exchange isoform 1 (NHE1) expression in
      hypertrophied myocytes. Thus, our results demonstrate an antihypertrophic effect
      of adenosine acting via multiple receptor subtypes through a mechanism involving
      down-regulation of NHE1 expression. The ability to prevent regulators of G
      protein signaling (RGS) up-regulation further suggests that adenosine receptor
      activation minimizes signaling which leads to hypertrophic responses.

PMID- 15452192
TI  - Long-term effect of treating pregnant rats with ursodeoxycholic acid on the
      congenital impairment of bile secretion induced in the pups by maternal
      cholestasis.
AB  - Transient latent cholestasis in young rats born from mothers with obstructive
      cholestasis during pregnancy (OCP) has been reported. The cause of this
      congenital impairment and the long-term effect on the pups of treating their
      mothers with ursodeoxycholic acid (UDCA) during pregnancy were investigated.
      Complete biliary obstruction was imposed on day 14 of pregnancy and UDCA
      treatment was begun on day 15. Serum bile acids (BAs) concentrations were
      elevated in 4-week-old pups born from OCP, but not OCP + UDCA, mothers. However,
      gas chromatographic/mass spectrometric analysis of BA species in basal bile
      indicated the presence of significant differences among all experimental groups
      (control, OCP, and OCP + UDCA). Canalicular plasma membrane fluidity was reduced
      in OCP, but not in OCP + UDCA, pups. Screening by reverse transcription followed
      by real-time quantitative polymerase chain reaction of the steady-state levels of
      mRNA of genes related to hepatobiliary function revealed changes (upregulation of
      Cyp7a1 and Mrp1 and down-regulation of Abcg5 and Abcg8) in OCP group, which were
      prevented by UDCA treatment. Electron microscopy examination showed multilamellar
      bodies occupying part of the canalicular lumen in OCP pups. Their number and size
      were reduced in animals born from OCP + UDCA mothers. In OCP, but not OCP + UDCA,
      the stimulation of bile flow and BA output induced by taurocholate administration
      were reduced and cholesterol/BA output ratio was increased, whereas
      phospholipid/BA output ratio was enhanced in both groups (OCP > OCP + UDCA). In
      conclusion, UDCA treatment of rats with cholestasis during pregnancy has long
      term beneficial effects on their offspring by preventing in part the congenital
      impairment in hepatobiliary function of the pups that affects their biliary lipid
      secretion.

PMID- 15452193
TI  - Dynamics of {beta}-amyloid reductions in brain, cerebrospinal fluid, and plasma
      of {beta}-amyloid precursor protein transgenic mice treated with a {gamma}
      secretase inhibitor.
AB  - gamma-Secretase inhibitors are one promising approach to the development of a
      therapeutic for Alzheimer's disease (AD). gamma-Secretase inhibitors reduce brain
      beta-amyloid peptide (Abeta), which is believed to be a major contributor in the
      etiology of AD. Transgenic mice overexpressing the human beta-amyloid precursor
      protein (APP) are valuable models to examine the dynamics of Abeta changes with
      gamma-secretase inhibitors in plaque-free and plaque-bearing animals. BMS-299897
      2-[(1R)-1-[[(4-chlorophenyl)sulfony](2,5-difluorophenyl)amino]ethyl]-5
      fluorobenzenepropanoic acid, a gamma-secretase inhibitor, showed dose- and time
      dependent reductions of Abeta in brain, cerebrospinal fluid (CSF), and plasma in
      young transgenic mice, with a significant correlation between brain and CSF Abeta
      levels. Because CSF and brain interstitial fluid are distinct compartments in
      composition and location, this correlation could not be assumed. In contrast,
      aged transgenic mice with large accumulations of Abeta in plaques showed
      reductions in CSF Abeta in the absence of measurable changes in plaque Abeta in
      the brain after up to 2 weeks of treatment. Hence, CSF Abeta levels were a
      valuable measure of gamma-secretase activity in the central nervous system in
      either the presence or absence of plaques. Transgenic mice were also used to
      examine potential side effects due to Notch inhibition. BMS-299897 was 15-fold
      more effective at preventing the cleavage of APP than of Notch in vitro. No
      changes in the maturation of CD8(+) thymocytes or of intestinal goblet cells were
      observed in mice treated with BMS-299897, showing that it is possible for gamma
      secretase inhibitors to reduce brain Abeta without causing Notch-mediated
      toxicity.

PMID- 15452194
TI  - Inhibitors of poly(ADP-ribose) polymerase modulate signal transduction pathways
      and secondary damage in experimental spinal cord trauma.
AB  - Poly(ADP-ribose) polymerase (PARP), a nuclear enzyme activated by strand breaks
      in DNA, plays an important role in the tissue injury associated with stroke and
      neurotrauma. The aim of our study was to evaluate the therapeutic efficacy of in
      vivo inhibition of PARP in an experimental model of spinal cord trauma, which was
      induced by the application of vascular clips (force of 24g) to the dura via a
      four-level T5-T8 laminectomy. Spinal cord injury in mice resulted in severe
      trauma characterized by edema, neutrophil infiltration (measured as an increase
      in myeloperoxidase activity), and apoptosis (measured by terminal
      deoxynucleotidyltransferase-mediated UTP end labeling coloration). Infiltration
      of spinal cord tissue with neutrophils was associated with a marked increase in
      immunoreactivity for poly(ADP-ribose) (PAR), index of PARP activation, in the
      spinal cord tissue. These inflammatory events were associated with the activation
      of nuclear factor-kappaB (NF-kappaB) at 4 h after spinal cord damage. Treatment
      of the mice with the PARP inhibitors 3-aminobenzamide (3-AB) or 5
      aminoisoquinolinone (5-AIQ) significantly reduced the degree of 1) spinal cord
      inflammation and tissue injury (histological score), 2) PAR formation, 3)
      neutrophil infiltration, and 4) apoptosis. Treatment with these PARP inhibitors
      also reduced DNA binding of NF-kappaB and inhibitory kappaB degradation. In a
      separate set of experiments, we have also demonstrated that PARP inhibitors
      significantly ameliorated the recovery of limb function (evaluated by motor
      recovery score). Taken together, our results clearly demonstrate that treatment
      with PARP inhibitors reduces the development of inflammation and tissue injury
      events associated with spinal cord trauma.

PMID- 15452195
TI  - Connections between connexins, calcium, and cataracts in the lens.
AB  - There is a good deal of evidence that the lens generates an internal micro
      circulatory system, which brings metabolites, like glucose, and antioxidants,
      like ascorbate, into the lens along the extracellular spaces between cells.
      Calcium also ought to be carried into the lens by this system. If so, the only
      path for Ca2+ to get out of the lens is to move down its electrochemical gradient
      into fiber cells, and then move by electrodiffusion from cell to cell through gap
      junctions to surface cells, where Ca-ATPase activity and Na/Ca exchange can
      transport it back into the aqueous or vitreous humors. The purpose of the present
      study was to test this calcium circulation hypothesis by studying calcium
      homeostasis in connexin (Cx46) knockout and (Cx46 for Cx50) knockin mouse lenses,
      which have different degrees of gap junction coupling. To measure intracellular
      calcium, FURA2 was injected into fiber cells, and the gradient in calcium
      concentration from center to surface was mapped in each type of lens. In wild
      type lenses the coupling conductance of the mature fibers was approximately 0.5
      S/cm2 of cell to cell contact, and the best fit to the calcium concentration data
      varied from 700 nM in the center to 300 nM at the surface. In the knockin lenses,
      the coupling conductance was approximately 1.0 S/cm2 and calcium varied from
      approximately 500 nM at the center to 300 nM at the surface. Thus, when the
      coupling conductance doubled, the concentration gradient halved, as predicted by
      the model. In knockout lenses, the coupling conductance was zero, hence the
      efflux path was knocked out and calcium accumulated to approximately 2 microM in
      central fibers. Knockout lenses also had a dense central cataract that extended
      from the center to about half the radius. Others have previously shown that this
      cataract involves activation of a calcium-dependent protease, Lp82. We can now
      expand on this finding to provide a hypothesis on each step that leads to
      cataract formation: knockout of Cx46 causes loss of coupling of mature fiber
      cells; the efflux path for calcium is therefore blocked; calcium accumulates in
      the central cells; at concentrations above approximately 1 microM (from the
      center to about half way out of a 3-wk-old lens) Lp82 is activated; Lp82 cleaves
      cytoplasmic proteins (crystallins) in central cells; and the cleaved proteins
      aggregate and scatter light.

PMID- 15452196
TI  - New insights on the voltage dependence of the KCa3.1 channel block by internal
      TBA.
AB  - We present in this work a structural model of the open IKCa (KCa3.1) channel
      derived by homology modeling from the MthK channel structure, and used this model
      to compute the transmembrane potential profile along the channel pore. This
      analysis showed that the selectivity filter and the region extending from the
      channel inner cavity to the internal medium should respectively account for 81%
      and 16% of the transmembrane potential difference. We found however that the
      voltage dependence of the IKCa block by the quaternary ammonium ion TBA applied
      internally is compatible with an apparent electrical distance delta of 0.49 +/-
      0.02 (n = 6) for negative potentials. To reconcile this observation with the
      electrostatic potential profile predicted for the channel pore, we modeled the
      IKCa block by TBA assuming that the voltage dependence of the block is governed
      by both the difference in potential between the channel cavity and the internal
      medium, and the potential profile along the selectivity filter region through an
      effect on the filter ion occupancy states. The resulting model predicts that
      delta should be voltage dependent, being larger at negative than positive
      potentials. The model also indicates that raising the internal K+ concentration
      should decrease the value of delta measured at negative potentials independently
      of the external K+ concentration, whereas raising the external K+ concentration
      should minimally affect delta for concentrations >50 mM. All these predictions
      are born out by our current experimental results. Finally, we found that the
      substitutions V275C and V275A increased the voltage sensitivity of the TBA block,
      suggesting that TBA could move further into the pore, thus leading to stronger
      interactions between TBA and the ions in the selectivity filter. Globally, these
      results support a model whereby the voltage dependence of the TBA block in IKCa
      is mainly governed by the voltage dependence of the ion occupancy states of the
      selectivity filter.

PMID- 15452197
TI  - The beta1 subunit enhances oxidative regulation of large-conductance calcium
      activated K+ channels.
AB  - Oxidative stress may alter the functions of many proteins including the Slo1
      large conductance calcium-activated potassium channel (BKCa). Previous results
      demonstrated that in the virtual absence of Ca2+, the oxidant chloramine-T (Ch
      T), without the involvement of cysteine oxidation, increases the open probability
      and slows the deactivation of BKCa channels formed by human Slo1 (hSlo1) alpha
      subunits alone. Because native BKCa channel complexes may include the auxiliary
      subunit beta1, we investigated whether beta1 influences the oxidative regulation
      of hSlo1. Oxidation by Ch-T with beta1 present shifted the half-activation
      voltage much further in the hyperpolarizing direction (-75 mV) as compared with
      that with alpha alone (-30 mV). This shift was eliminated in the presence of high
      [Ca2+]i, but the increase in open probability in the virtual absence of Ca2+
      remained significant at physiologically relevant voltages. Furthermore, the
      slowing of channel deactivation after oxidation was even more dramatic in the
      presence of beta1. Oxidation of cysteine and methionine residues within beta1 was
      not involved in these potentiated effects because expression of mutant beta1
      subunits lacking cysteine or methionine residues produced results similar to
      those with wild-type beta1. Unlike the results with alpha alone, oxidation by Ch
      T caused a significant acceleration of channel activation only when beta1 was
      present. The beta1 M177 mutation disrupted normal channel activation and
      prevented the Ch-T-induced acceleration of activation. Overall, the functional
      effects of oxidation of the hSlo1 pore-forming alpha subunit are greatly
      amplified by the presence of beta1, which leads to the additional increase in
      channel open probability and the slowing of deactivation. Furthermore, M177
      within beta1 is a critical structural determinant of channel activation and
      oxidative sensitivity. Together, the oxidized BKCa channel complex with beta1 has
      a considerable chance of being open within the physiological voltage range even
      at low [Ca2+]i.

PMID- 15452198
TI  - Determinants of anion permeation in the second transmembrane domain of the mouse
      bestrophin-2 chloride channel.
AB  - Bestrophins have been proposed to constitute a new family of Cl channels that are
      activated by cytosolic Ca. We showed previously that mutation of serine-79 to
      cysteine in mouse bestrophin-2 (mBest2) altered the relative permeability and
      conductance to SCN. In this paper, we have overexpressed various mutant
      constructs of mBest2 in HEK-293 cells to explore the contributions to anion
      selectivity of serine-79 and other amino acids (V78, F80, G83, F84, V86, and T87)
      located in the putative second transmembrane domain (TMD2). Residues selected for
      mutagenesis were distributed throughout TMD2, but mutations at all positions
      changed the selectivity. The effects on selectivity were rather modest.
      Replacement of residues 78, 79, 80, 83, 84, 86, or 87 with cysteine had similar
      effects: the permeability of the channel to SCN relative to Cl (PSCN/PCl) was
      decreased three- to fourfold and the relative SCN conductance (GSCN/GCl) was
      increased five- to tenfold. Side chains at positions 78 and 80 appeared to be
      situated close to the permeant anion, because the electrostatic charge at these
      positions affected permeation in specific ways. The effects of charged sulfhydryl
      reactive MTS reagents were the opposite in the V78C and F80C mutants and the
      effects were partially mimicked by substitution of F80 with charged amino acids.
      In S79T, switching from Cl to SCN caused slow changes in GSCN/GCl (tau = 16.6 s),
      suggesting that SCN binding to the channel altered channel gating as well as
      conductance. The data in this paper and other data support a model in which TMD2
      plays an important role in forming the bestrophin pore. We suggest that the major
      determinant in anion permeation involves partitioning of the permeant anion into
      an aqueous pore whose structural features are rather flexible. Furthermore, anion
      permeation and gating may be linked.

PMID- 15452199
TI  - Identification of the Ca2+ blocking site of acid-sensing ion channel (ASIC) 1:
      implications for channel gating.
AB  - Acid-sensing ion channels ASIC1a and ASIC1b are ligand-gated ion channels that
      are activated by H+ in the physiological range of pH. The apparent affinity for
      H+ of ASIC1a and 1b is modulated by extracellular Ca2+ through a competition
      between Ca2+ and H+. Here we show that, in addition to modulating the apparent H+
      affinity, Ca2+ blocks ASIC1a in the open state (IC50 approximately 3.9 mM at pH
      5.5), whereas ASIC1b is blocked with reduced affinity (IC50 > 10 mM at pH 4.7).
      Moreover, we report the identification of the site that mediates this open
      channel block by Ca2+. ASICs have two transmembrane domains. The second
      transmembrane domain M2 has been shown to form the ion pore of the related
      epithelial Na+ channel. Conserved topology and high homology in M2 suggests that
      M2 forms the ion pore also of ASICs. Combined substitution of an aspartate and a
      glutamate residue at the beginning of M2 completely abolished block by Ca2+ of
      ASIC1a, showing that these two amino acids (E425 and D432) are crucial for Ca2+
      block. It has previously been suggested that relief of Ca2+ block opens ASIC3
      channels. However, substitutions of E425 or D432 individually or in combination
      did not open channels constitutively and did not abolish gating by H+ and
      modulation of H+ affinity by Ca2+. These results show that channel block by Ca2+
      and H+ gating are not intrinsically linked.

PMID- 15452200
TI  - Mechanisms of regulation of epithelial sodium channel by SGK1 in A6 cells.
AB  - The serum and glucocorticoid induced kinase 1 (SGK1) participates in the
      regulation of sodium reabsorption in the distal segment of the renal tubule,
      where it may modify the function of the epithelial sodium channel (ENaC). The
      molecular mechanism underlying SGK1 regulation of ENaC in renal epithelial cells
      remains controversial. We have addressed this issue in an A6 renal epithelial
      cell line that expresses SGK1 under the control of a tetracycline-inducible
      system. Expression of a constitutively active mutant of SGK1 (SGK1T(S425D))
      induced a sixfold increase in amiloride-sensitive short-circuit current (Isc).
      Using noise analysis we demonstrate that SGK1 effect on Isc is due to a fourfold
      increase in the number of functional ENaCs in the membrane and a 43% increase in
      channel open probability. Impedance analysis indicated that SGK1T(S425D)
      increased the absolute value of cell equivalent capacitance by an average of
      13.7%. SGK1T(S425D) also produced a 1.6-1.9-fold increase in total and plasma
      membrane subunit abundance, without changing the half-life of channels in the
      membrane. We conclude that in contrast to aldosterone, where stimulation of
      transport can be explained simply by an increase in channel synthesis, SGK1
      effects are more complex and involve at least three actions: (1) increase of ENaC
      open probability; (2) increase of subunit abundance within apical membranes and
      intracellular compartments; and (3) activation of one or more pools of
      preexistent channels within the apical membranes and/or intracellular
      compartments.

PMID- 15452201
TI  - Regulation of Ca2+ sparks by Ca2+ and Mg2+ in mammalian and amphibian muscle. An
      RyR isoform-specific role in excitation-contraction coupling?
AB  - Ca2+ and Mg2+ are important mediators and regulators of intracellular Ca2+
      signaling in muscle. The effects of changes of cytosolic [Ca2+] or [Mg2+] on
      elementary Ca2+ release events were determined, as functions of concentration and
      time, in single fast-twitch permeabilized fibers of rat and frog. Ca2+ sparks
      were identified and their parameters measured in confocal images of fluo-4
      fluorescence. Solutions with different [Ca2+] or [Mg2+] were rapidly exchanged
      while imaging. Faster and spatially homogeneous changes of [Ca2+] (reaching peaks
      >100 microM) were achieved by photolysing Ca NP-EGTA with laser flashes. In both
      species, incrementing cytosolic [Ca2+] caused a steady, nearly proportional
      increase in spark frequency, reversible upon [Ca2+] reduction. A greater change
      in spark frequency, usually transient, followed sudden increases in [Ca2+] after
      a lag of 100 ms or more. The nonlinearity, lag, and other features of this
      delayed effect suggest that it requires increase of [Ca2+] inside the SR. In the
      frog only, increases in cytosolic [Ca2+] often resulted, after a lag, in sparks
      that propagated transversally. An increase in [Mg2+] caused a fall of spark
      frequency, but with striking species differences. In the rat, but not the frog,
      sparks were observed at 4-40 mM [Mg2+]. Reducing [Mg2+] below 2 mM, which should
      enable the RyR channel's activation (CICR) site to bind Ca2+, caused progressive
      increase in spark frequency in the frog, but had no effect in the rat. Spark
      propagation and enhancement by sub-mM Mg2+ are hallmarks of CICR. Their absence
      in the rat suggests that CICR requires RyR3 para-junctional clusters, present
      only in the frog. The observed frequency of sparks corresponds to a channel open
      probability of 10(-7) in the frog or 10(-8) in the rat. Together with the failure
      of photorelease to induce activation directly, this indicates a basal inhibition
      of channels in situ. It is proposed that relief of this inhibition could be the
      mechanism by which increased SR load increases spark frequency.

PMID- 15452202
TI  - Physiological and microfluorometric studies of reduction and clearance of retinal
      in bleached rod photoreceptors.
AB  - The visual cycle comprises a sequence of reactions that regenerate the visual
      pigment in photoreceptors during dark adaptation, starting with the reduction of
      all-trans retinal to all-trans retinol and its clearance from photoreceptors. We
      have followed the reduction of retinal and clearance of retinol within bleached
      outer segments of red rods isolated from salamander retina by measuring its
      intrinsic fluorescence. Following exposure to a bright light (bleach), increasing
      fluorescence intensity was observed to propagate along the outer segments in a
      direction from the proximal region adjacent to the inner segment toward the
      distal tip. Peak retinol fluorescence was achieved after approximately 30 min,
      after which it declined very slowly. Clearance of retinol fluorescence is
      considerably accelerated by the presence of the exogenous lipophilic substances
      IRBP (interphotoreceptor retinoid binding protein) and serum albumin. We have
      used simultaneous fluorometric and electrophysiological measurements to compare
      the rate of reduction of all-trans retinal to all-trans retinol to the rate of
      recovery of flash response amplitude in these cells in the presence and absence
      of IRBP. We find that flash response recovery in rods is modestly accelerated in
      the presence of extracellular IRBP. These results suggest such substances may
      participate in the clearance of retinoids from rod photoreceptors, and that this
      clearance, at least in rods, may facilitate dark adaptation by accelerating the
      clearance of photoproducts of bleaching.

PMID- 15452203
TI  - Gene silencing in alveolar type II cells using cell-specific promoter in vitro
      and in vivo.
AB  - RNA interference (RNAi) is a sequence-specific post-transcriptional gene
      silencing process. Although it is widely used in the loss-of-function studies,
      none of the current RNAi technologies can achieve cell-specific gene silencing.
      The lack of cell specificity limits its usage in vivo. Here, we report a cell
      specific RNAi system using an alveolar epithelial type II cell-specific promoter-
      the surfactant protein C (SP-C) promoter. We show that the SP-C-driven small
      hairpin RNAs specifically depress the expression of the exogenous reporter
      (enhanced green fluorescent protein) and endogenous genes (lamin A/C and annexin
      A2) in alveolar type II cells, but not other lung cells, using cell and organ
      culture in vitro as well as in vivo. The present study provides an efficient
      strategy in silencing a gene in one type of cell without interfering with other
      cell systems, and may have a significant impact on RNAi therapy.

PMID- 15452204
TI  - VP7 mediates the interaction of rotaviruses with integrin alphavbeta3 through a
      novel integrin-binding site.
AB  - Rotavirus entry is a complex multistep process that depends on the trypsin
      cleavage of the virus spike protein VP4 into polypeptides VP5 and VP8 and on the
      interaction of these polypeptides and of VP7, the second viral surface protein,
      with several cell surface molecules, including integrin alphavbeta3. We
      characterized the effect of the trypsin cleavage of VP4 on the binding to MA104
      cells of the sialic acid-dependent virus strain RRV and its sialic acid
      independent variant, nar3. We found that, although the trypsin treatment did not
      affect the attachment of these viruses to the cell surface, their binding was
      qualitatively different. In contrast to the trypsin-treated viruses, which
      initially bound to the cell surface through VP4, the non-trypsin-treated variant
      nar3 bound to the cell through VP7. Amino acid sequence comparison of the surface
      proteins of rotavirus and hantavirus, both of which interact with integrin
      alphavbeta3 in an RGD-independent manner, identified a region shared by rotavirus
      VP7 and hantavirus G1G2 protein in which six of nine amino acids are identical.
      This region, which is highly conserved among the VP7 proteins of different
      rotavirus strains, mediates the binding of rotaviruses to integrin alphavbeta3
      and probably represents a novel binding motif for this integrin.

PMID- 15452205
TI  - Lentivirus-mediated RNA interference of DC-SIGN expression inhibits human
      immunodeficiency virus transmission from dendritic cells to T cells.
AB  - In the early events of human immunodeficiency virus type 1 (HIV-1) infection,
      immature dendritic cells (DCs) expressing the DC-specific intercellular adhesion
      molecule 3-grabbing nonintegrin (DC-SIGN) receptor capture small amounts of HIV-1
      on mucosal surfaces and spread viral infection to CD4(+) T cells in lymph nodes
      (22, 34, 45). RNA interference has emerged as a powerful tool to gain insight
      into gene function. For this purpose, lentiviral vectors that express short
      hairpin RNA (shRNA) for the delivery of small interfering RNA (siRNA) into
      mammalian cells represent a powerful tool to achieve stable gene silencing. In
      order to interfere with DC-SIGN function, we developed shRNA-expressing
      lentiviral vectors capable of conditionally suppressing DC-SIGN expression.
      Selectivity of inhibition of human DC-SIGN and L-SIGN and chimpanzee and rhesus
      macaque DC-SIGN was obtained by using distinct siRNAs. Suppression of DC-SIGN
      expression inhibited the attachment of the gp120 envelope glycoprotein of HIV-1
      to DC-SIGN transfectants, as well as transfer of HIV-1 to target cells in trans.
      Furthermore, shRNA-expressing lentiviral vectors were capable of efficiently
      suppressing DC-SIGN expression in primary human DCs. DC-SIGN-negative DCs were
      unable to enhance transfer of HIV-1 infectivity to T cells in trans,
      demonstrating an essential role for the DC-SIGN receptor in transferring
      infectious viral particles from DCs to T cells. The present system should have
      broad applications for studying the function of DC-SIGN in the pathogenesis of
      HIV as well as other pathogens also recognized by this receptor.

PMID- 15452206
TI  - Nuclear respiratory factor 1 plays an essential role in transcriptional
      initiation from the hepatitis B virus x gene promoter.
AB  - The X gene of hepatitis B virus (HBV) is one of the major factors in HBV-induced
      hepatocarcinogenesis and is essential for the establishment of productive HBV
      replication in vivo. Recent studies have shown that the X gene product targets
      mitochondria and induces calcium flux, thereby activating Ca(+)-dependent signal
      transduction pathways. However, regulatory mechanisms of X gene expression have
      remained unclear. Previous studies had localized a minimal promoter activity to a
      21-bp GC-rich sequence located 130 bp upstream of the X protein coding region and
      showed that there was a cellular protein bound to this DNA. Interestingly, the 21
      bp sequence identified as an X gene minimal promoter does not contain any
      previously identified core promoter elements, such as a TATA box. To better
      understand the mechanisms of transcriptional initiation of the X gene, we set out
      to biochemically purify the binding protein(s) for the 21-bp DNA. We report here
      the identification of the X gene minimal promoter-binding activity as nuclear
      respiratory factor 1 (NRF1), a previously known transcription factor that
      activates the majority of nucleus-encoded mitochondrial genes and various
      housekeeping genes. Primer extension analyses of the X mRNAs show that mutations
      at the binding site specifically inactivate transcription from this promoter and
      that a dominant-negative NRF1 mutant and short interfering RNAs inhibit
      transcription from this promoter. Therefore, NRF1 specifically binds the 21-bp
      minimal promoter and positively contributes to transcription of the X gene.
      Simultaneous activation of the X gene and mitochondrial genes by NRF1 may allow
      the X protein to target mitochondria most efficiently.

PMID- 15452207
TI  - cis-acting RNA signals in the NS5B C-terminal coding sequence of the hepatitis C
      virus genome.
AB  - The cis-replicating RNA elements in the 5' and 3' nontranslated regions (NTRs) of
      the hepatitis C virus (HCV) genome have been thoroughly studied before. However,
      no cis-replicating elements have been identified in the coding sequences of the
      HCV polyprotein until very recently. The existence of highly conserved and stable
      stem-loop structures in the RNA polymerase NS5B coding sequence, however, has
      been previously predicted (A. Tuplin, J. Wood, D. J. Evans, A. H. Patel, and P.
      Simmonds, RNA 8:824-841, 2002). We have selected for our studies a 249-nt-long
      RNA segment in the C-terminal NS5B coding region (NS5BCR), which is predicted to
      form four stable stem-loop structures (SL-IV to SL-VII). By deletion and
      mutational analyses of the RNA structures, we have determined that two of the
      stem-loops (SL-V and SL-VI) are essential for replication of the HCV subgenomic
      replicon in Huh-7 cells. Mutations in the loop and the top of the stem of these
      RNA elements abolished replicon RNA synthesis but had no effect on translation.
      In vitro gel shift and filter-binding assays revealed that purified NS5B
      specifically binds to SL-V. The NS5B-RNA complexes were specifically competed
      away by unlabeled homologous RNA, to a small extent by 3' NTR RNA, and only
      poorly by 5' NTR RNA. The other two stem-loops (SL-IV and SL-VII) of the NS5BCR
      domain were found to be important but not essential for colony formation by the
      subgenomic replicon. The precise function(s) of these cis-acting RNA elements is
      not known.

PMID- 15452208
TI  - LMP2A does not require palmitoylation to localize to buoyant complexes or for
      function.
AB  - Epstein-Barr virus (EBV) latent membrane protein 2A (LMP2A) is expressed
      constitutively in lipid rafts in latently infected B lymphocytes. Lipid rafts are
      membrane microdomains enriched in cholesterol and sphingolipids selective for
      specific protein association. Lipid rafts have been shown to be necessary for B
      cell receptor (BCR) signal transduction. LMP2A prevents BCR recruitment to lipid
      rafts, thereby abrogating BCR function. As LMP2A is palmitoylated, whether this
      fatty acid modification is necessary for LMP2A to localize to lipid rafts and for
      protein function was investigated. LMP2A palmitoylation was confirmed in latently
      infected B cells. LMP2A was found to be palmitoylated on multiple cysteines only
      by S acylation. An LMP2A mutant that was not palmitoylated was identified and
      functioned similar to wild-type LMP2A; unmodified LMP2A localized to lipid rafts,
      was tyrosine phosphorylated, was associated with LMP2A-associated proteins, was
      ubiquitinated, and was able to block calcium mobilization following BCR cross
      linking. Therefore, palmitoylation of LMP2A is not required for LMP2A targeting
      to buoyant complexes or for function.

PMID- 15452209
TI  - Identification of an hnRNP A1-dependent splicing silencer in the human
      papillomavirus type 16 L1 coding region that prevents premature expression of the
      late L1 gene.
AB  - We have previously identified cis-acting RNA sequences in the human
      papillomavirus type 16 (HPV-16) L1 coding region which inhibit expression of L1
      from eukaryotic expression plasmids. Here we have determined the function of one
      of these RNA elements, and we provide evidence that this RNA element is a
      splicing silencer which suppresses the use of the 3' splice site located
      immediately upstream of the L1 AUG. We also show that this splice site is
      inefficiently utilized as a result of a suboptimal polypyrimidine tract.
      Introduction of point mutations in the L1 coding region that altered the RNA
      sequence without affecting the L1 protein sequence resulted in the inactivation
      of the splicing silencer and induced splicing to the L1 3' splice site. These
      mutations also prevented the interaction of the RNA silencer with a 35-kDa
      cellular protein identified here as hnRNP A1. The splicing silencer in L1
      inhibits splicing in vitro, and splicing can be restored by the addition of RNAs
      containing an hnRNP A1 binding site to the reaction, demonstrating that hnRNP A1
      inhibits splicing of the late HPV-16 mRNAs through the splicing silencer
      sequence. While we show that one role of the splicing silencer is to determine
      the ratio between partially spliced L2/L1 mRNAs and spliced L1 mRNAs, we also
      demonstrate that it inhibits splicing from the major 5' splice site in the early
      region to the L1 3' splice site, thereby playing an essential role in preventing
      late gene expression at an early stage of the viral life cycle. We speculate that
      the activity of the splicing silencer and possibly the concentration of hnRNP A1
      in the HPV-16-infected cell determines the ability of the virus to establish a
      persistent infection which remains undetected by the host immune surveillance.

PMID- 15452210
TI  - Early bone marrow hematopoietic defect in simian/human immunodeficiency virus
      C2/1-infected macaques and relevance to advance of disease.
AB  - To clarify hematological abnormalities following infection with human
      immunodeficiency virus (HIV), we examined the hematopoietic capability of bone
      marrow by using cynomolgus monkeys infected with pathogenic simian/human
      immunodeficiency virus (SHIV) strain C2/1, an animal model of HIV infection. The
      relationship between the progress of the infection and the CD4/CD8 ratio of T
      lymphocytes or the amount of SHIV C2/1 viral load in the peripheral blood was
      also investigated. A colony assay was performed to assess the hematopoietic
      capability of bone marrow stem cells during the early and advanced phases of the
      infection. Colonies of granulocytes-macrophages (GM) were examined by PCR for the
      presence of the SIVmac239 gag region to reveal direct viral infection. There was
      a remarkable decrease in the CFU-GM growth on days 1 and 3 postinoculation,
      followed by recovery on day 56. During the more advanced stage, the CFU-GM growth
      decreased again. There was minimal evidence of direct viral infection of pooled
      cultured CFU-GM despite the continuously low CD4/CD8 ratios. These results
      indicate that the decrease in colony formation by bone marrow stem cells is
      reversible and fluctuates with the advance of the disease. This decrease was not
      due to direct viral infection of CFU-GM. Our data may support the concept that,
      in the early phase, production of inhibitory factors or deficiency of a
      stimulatory cytokine is responsible for some of the bone marrow defects described
      in the SHIV C2/1 model.

PMID- 15452211
TI  - Splice junction map of simian parvovirus transcripts.
AB  - The transcription map of simian parvovirus (SPV), an Erythrovirus similar to
      Parvovirus B19, was investigated. RNA was extracted from tissues of
      experimentally infected cynomolgus macaques and subjected to reverse
      transcription-PCR with SPV-specific primers. The PCR products were cloned and
      sequenced to identify splice junctions. A total of 14 distinct sequences were
      identified as putative partial transcripts. Of these, 13 were spliced; a single
      unspliced transcript putatively encoded NS1. Sequence analysis revealed that
      spliced partial transcripts may encode portions of open reading frames for the
      major capsid proteins VP1 and VP2 and smaller, unknown proteins. These unspliced
      and spliced transcripts and putative proteins encoded by SPV were similar to
      those of B19. Initial splice junctions at nucleotides 279 and 333 were analogous
      to those at nucleotides 406 and 441, respectively, in B19. Seven of the 10
      splices identified had typical GT/AG donor/acceptor junctions. The splice sites
      were confirmed by Northern blotting and autoradiography. In contrast to B19,
      which has a maximum of two splices per transcript, up to three splices were
      observed in SPV transcripts. A spliced transcript putatively encoding a truncated
      version of NS1, as seen with minute virus of mice and adeno-associated virus 2,
      was also observed. The findings indicate that that the splicing pattern of
      transcripts of SPV and B19 is similar, but SPV also has coding strategies in
      common with other parvoviruses.

PMID- 15452212
TI  - Phosphatidylserine is not the cell surface receptor for vesicular stomatitis
      virus.
AB  - The envelope protein from vesicular stomatitis virus (VSV) has become an
      important tool for gene transfer and gene therapy. It is widely used mainly
      because of its ability to mediate virus entry into all cell types tested to date.
      Consistent with the broad tropism of the virus, the receptor for VSV is thought
      to be a ubiquitous membrane lipid, phosphatidylserine (PS). However, the evidence
      for this hypothesis is indirect and incomplete. Here, we have examined the
      potential interaction of VSV and PS at the plasma membrane in more detail.
      Measurements of cell surface levels of PS show a wide range across cell types
      from different organisms. We demonstrate that there is no correlation between the
      cell surface PS levels and VSV infection or binding. We also demonstrate that an
      excess of annexin V, which binds specifically and tightly to PS, does not inhibit
      infection or binding by VSV. While the addition of PS to cells does allow
      increased virus entry, we show that this effect is not specific to the VSV
      envelope. We conclude that PS is not the cell surface receptor for VSV, although
      it may be involved in a postbinding step of virus entry.

PMID- 15452213
TI  - mRNA molecules containing murine leukemia virus packaging signals are
      encapsidated as dimers.
AB  - Prior work by others has shown that insertion of psi (i.e., leader) sequences
      from the Moloney murine leukemia virus (MLV) genome into the 3' untranslated
      region of a nonviral mRNA leads to the specific encapsidation of this RNA in MLV
      particles. We now report that these RNAs are, like genomic RNAs, encapsidated as
      dimers. These dimers have the same thermostability as MLV genomic RNA dimers;
      like them, these dimers are more stable if isolated from mature virions than from
      immature virions. We characterized encapsidated mRNAs containing deletions or
      truncations of MLV psi or with psi sequences from MLV-related acute transforming
      viruses. The results indicate that the dimeric linkage in genomic RNA can be
      completely attributed to the psi region of the genome. While this conclusion
      agrees with earlier electron microscopic studies on mature MLV dimers, it is the
      first evidence as to the site of the linkage in immature dimers for any
      retrovirus. Since the Psi(+) mRNA is not encapsidated as well as genomic RNA, it
      is only present in a minority of virions. The fact that it is nevertheless
      dimeric argues strongly that two of these molecules are packaged into particles
      together. We also found that the kissing loop is unnecessary for this
      coencapsidation or for the stability of mature dimers but makes a major
      contribution to the stability of immature dimers. Our results are consistent with
      the hypothesis that the packaging signal involves a dimeric structure in which
      the RNAs are joined by intermolecular interactions between GACG loops.

PMID- 15452214
TI  - The DNA element controlling expression of the varicella-zoster virus open reading
      frame 28 and 29 genes consists of two divergent unidirectional promoters which
      have a common USF site.
AB  - The mechanism of the divergent expression of the varicella-zoster virus (VZV) ORF
      28 and ORF 29 genes from a common intergenic DNA element, the ORF 28/29 promoter,
      is of interest based on the observation that both genes are expressed during VZV
      lytic infection but only the ORF 29 gene is expressed in latently infected
      neurons. In the work presented here, expression driven by the ORF 28/29
      intergenic region was examined. We found that the promoter activity towards the
      ORF 29 direction is more responsive to activation by the major viral
      transactivator IE62 than that towards the ORF 28 direction in the context of our
      experimental system. Analysis of the functional DNA elements involved in IE62
      activation of the bidirectional ORF 28/29 regulatory element revealed that in
      both transfected and VZV-superinfected cells it is a fusion of two unidirectional
      promoters overlapping an essential USF binding site but with distinct TATA
      elements. A single TATA element directs expression in the ORF 28 direction,
      whereas the two TATA elements directing ORF 29 gene expression are alternatively
      and differentially utilized for transcription initiation. We also identified an
      Sp1 site localized proximal to the ORF 28 gene which functions as an activator
      element for expression in both directions. These results indicate that the ORF 28
      and ORF 29 genes can be expressed either coordinately or independently and that
      the observed expression of only the ORF 29 gene during VZV latency may involve
      neuron-specific cellular factors and/or structural aspects of the latent viral
      genome.

PMID- 15452215
TI  - Enhanced expression of cell cycle regulatory genes in virus-specific memory CD8+
      T cells.
AB  - Unlike naive CD8+ T cells, antigen-experienced memory CD8+ T cells persist over
      time due to their unique ability to homeostatically proliferate. It was
      hypothesized that memory cells might differentially regulate the expression of
      genes that control the cell cycle to facilitate homeostatic proliferation. To
      test this, the expression levels of 96 different cell cycle regulatory genes were
      compared between transgenic naive and memory CD8+ T cells that specifically
      recognize the GP33-41 epitope of lymphocytic choriomeningitis virus (LCMV). It
      was discovered that relative to naive cells, memory cells overexpress several
      important genes that control the transition between G(1) and S phase. Some of
      these genes include those encoding cyclins D3, D2, B1, C, and H, cyclin-dependent
      kinases (cdk's) 4 and 6, the cdk inhibitors p16, p15, and p18, and other genes
      involved in protein degradation and DNA replication. Importantly, these
      differences were observed both in total populations of LCMV-specific naive and
      memory CD8+ cells and in LCMV-specific CD8+ T-cell populations that were in the
      G(1) phase of the cell cycle only. In addition, the expression differences
      between naive and memory cells were exaggerated following antigenic stimulation.
      The fact that memory cells are precharged with several of the major factors that
      are necessary for the G(1)- to-S-phase transition suggests they may require a
      lower threshold of stimulation to enter the cell cycle.

PMID- 15452216
TI  - Identification of proteins in human cytomegalovirus (HCMV) particles: the HCMV
      proteome.
AB  - Human cytomegalovirus (HCMV), a member of the herpesvirus family, is a large
      complex enveloped virus composed of both viral and cellular gene products. While
      the sequence of the HCMV genome has been known for over a decade, the full set of
      viral and cellular proteins that compose the HCMV virion are unknown. To approach
      this problem we have utilized gel-free two-dimensional capillary liquid
      chromatography-tandem mass spectrometry (MS/MS) and Fourier transform ion
      cyclotron resonance MS to identify and determine the relative abundances of viral
      and cellular proteins in purified HCMV AD169 virions and dense bodies. Analysis
      of the proteins from purified HCMV virion preparations has indicated that the
      particle contains significantly more viral proteins than previously known. In
      this study, we identified 71 HCMV-encoded proteins that included 12 proteins
      encoded by known viral open reading frames (ORFs) previously not associated with
      virions and 12 proteins from novel viral ORFs. Analysis of the relative abundance
      of HCMV proteins indicated that the predominant virion protein was the pp65
      tegument protein and that gM rather than gB was the most abundant glycoprotein.
      We have also identified over 70 host cellular proteins in HCMV virions, which
      include cellular structural proteins, enzymes, and chaperones. In addition,
      analysis of HCMV dense bodies indicated that these viral particles are composed
      of 29 viral proteins with a reduced quantity of cellular proteins in comparison
      to HCMV virions. This study provides the first comprehensive quantitative
      analysis of the viral and cellular proteins that compose infectious particles of
      a large complex virus.

PMID- 15452217
TI  - Maturation and trafficking markers on rotavirus-specific B cells during acute
      infection and convalescence in children.
AB  - We have previously studied B cells, from people and mice, that express rotavirus
      specific surface immunoglobulin (RV-sIg) by flow cytometry with recombinant virus
      like particles that contain green fluorescent protein. In the present study we
      characterized circulating B cells with RV-sIg in children with acute and
      convalescent infection. During acute infection, circulating RV-sIgD(-) B cells
      are predominantly large, CD38(high), CD27(high), CD138(+/-), CCR6(-),
      alpha4beta7(+), CCR9(+), CCR10(+), cutaneous lymphocyte antigen-negative (CLA(
      )), L-selectin(int/-), and sIgM(+), sIgG(-), sIgA(+/-) lymphocytes. This
      phenotype likely corresponds to gut-targeted plasma cells and plasmablasts.
      During convalescence the phenotype switches to small and large lymphocytes,
      CD38(int/-), CD27(int/-), CCR6(+), alpha4beta7(+/-), CCR9(+/-) and CCR10(-), most
      likely representing RV-specific memory B cells with both gut and systemic
      trafficking profiles. Of note, during acute RV infection both total and RV
      specific murine IgM and IgA antibody-secreting cells migrate efficiently to CCL28
      (the CCR10 ligand) and to a lesser extent to CCL25 (the CCR9 ligand). Our results
      show that CCR10 and CCR9 can be expressed on IgM as well as IgA antibody
      secreting cells in response to acute intestinal infection, likely helping target
      these cells to the gut. However, these intestinal infection-induced plasmablasts
      lack the CLA homing receptor for skin, consistent with mechanisms of differential
      CCR10 participation in skin T versus intestinal plasma cell homing.
      Interestingly, RV memory cells generally lack CCR9 and CCR10 and instead express
      CCR6, which may enable recruitment to diverse epithelial sites of inflammation.

PMID- 15452218
TI  - Herpes simplex virus type 1 ICP0 protein mediates activation of adeno-associated
      virus type 2 rep gene expression from a latent integrated form.
AB  - Adeno-associated virus type 2 (AAV-2) is a human parvovirus that requires the
      presence of a helper virus, such as the herpes simplex virus type 1 (HSV-1) to
      accomplish a complete productive cycle. In the absence of helper virus, AAV-2 can
      establish a latent infection that is characterized by the absence of expression
      of viral genes. So far, four HSV-1 early genes, UL5/8/52 (helicase primase
      complex) and UL29 (single-stranded DNA-binding protein), were defined as
      sufficient for AAV replication when cells were transfected with a plasmid
      carrying the wild-type AAV-2 genome. However, none of these viral products was
      shown to behave as a transcriptional factor able to activate AAV gene expression.
      Our study provides the first evidence that the immediate-early HSV-1 protein ICP0
      can promote rep gene expression in cells latently infected with wild-type AAV-2.
      This ICP0-mediated effect occurs at the transcriptional level and involves the
      ubiquitin-proteasome pathway. Furthermore, using deletion mutants, we demonstrate
      that the localization of ICP0 to ND10 and their disruption is not required for
      the activation of the rep promoter, whereas binding of ICP0 to the ubiquitin
      specific protease HAUSP makes a significant contribution to this effect.

PMID- 15452219
TI  - Spike protein VP4 assembly with maturing rotavirus requires a postendoplasmic
      reticulum event in polarized caco-2 cells.
AB  - Rotavirus assembly is a multistep process that requires the successive
      association of four major structural proteins in three concentric layers. It has
      been assumed until now that VP4, the most external viral protein that forms the
      spikes of mature virions, associates with double-layer particles within the
      endoplasmic reticulum (ER) in conjunction with VP7 and with the help of a
      nonstructural protein, NSP4. VP7 and NSP4 are two glycosylated proteins. However,
      we recently described a strong association of VP4 with raft-type membrane
      microdomains, a result that makes the ER a highly questionable site for the final
      assembly of rotavirus, since rafts are thought to be absent from this
      compartment. In this study, we used tunicamycin (TM), a drug known to block the
      first step of protein N glycosylation, as a tool to dissect rotavirus assembly.
      We show that, as expected, TM blocks viral protein glycosylation and also
      decreases virus infectivity. In the meantime, viral particles were blocked as
      enveloped particles in the ER. Interestingly, TM does not prevent the targeting
      of VP4 to the cell surface nor its association with raft membranes, whereas the
      infectivity associated with the raft fractions strongly decreased. VP4 does not
      colocalize with the ER marker protein disulfide-isomerase even when viral
      particles were blocked by TM in this compartment. These results strongly support
      a primary role for raft membranes in rotavirus final assembly and the fact that
      VP4 assembly with the rest of the particle is an extrareticular event.

PMID- 15452220
TI  - Major human cytomegalovirus structural protein pp65 (ppUL83) prevents interferon
      response factor 3 activation in the interferon response.
AB  - We have identified a cytomegalovirus virion protein capable of modulating the
      rapid induction of an interferon-like response in cells that follows virus
      binding and penetration. Functional genomics revealed a role for the major
      cytomegalovirus structural protein, pp65 (ppUL83), in counteracting this
      response. The underlying mechanism involves a differential impact of this
      structural protein on the regulation of interferon response factor 3 (IRF-3). In
      contrast, NF-kappaB is activated independent of pp65, and neither STAT1 nor STAT3
      becomes activated by either virus. pp65 is sufficient to prevent the activation
      of IRF-3 when introduced alone into cells. pp65 acts by inhibiting nuclear
      accumulation of IRF-3 and is associated with a reduced IRF-3 phosphorylation
      state. Thus, this investigation shows that the major structural protein of
      cytomegalovirus is committed to the modulation of the IRF-3 response, a primary
      mediator of the type I interferon response. By subverting IRF-3, the virus
      escapes throwing a central alarm devoted to both immediate antiviral control and
      regulation of the immune response.

PMID- 15452221
TI  - Influenza B virus BM2 protein is a crucial component for incorporation of viral
      ribonucleoprotein complex into virions during virus assembly.
AB  - Influenza B virus contains four integral membrane proteins in its envelope. Of
      these, BM2 has recently been found to have ion channel activity and is considered
      to be a functional counterpart to influenza A virus M2, but the role of BM2 in
      the life cycle of influenza B virus remains unclear. In an effort to explore its
      function, a number of BM2 mutant viruses were generated by using a reverse
      genetics technique. The BM2DeltaATG mutant virus synthesized BM2 at markedly
      lower levels but exhibited similar growth to wild-type (wt) virus. In contrast,
      the BM2 knockout virus, which did not produce BM2, did not grow substantially but
      was able to grow normally when BM2 was supplemented in trans by host cells
      expressing BM2. These results indicate that BM2 is a required component for the
      production of infectious viruses. In the one-step growth cycle, the BM2 knockout
      virus produced progeny viruses lacking viral ribonucleoprotein complex (vRNP).
      The inhibited incorporation of vRNP was regained by trans-supplementation of BM2.
      An immunofluorescence study of virus-infected cells revealed that distribution of
      hemagglutinin, nucleoprotein, and matrix (M1) protein of the BM2 knockout virus
      at the apical membrane did not differ from that of wt virus, whereas the sucrose
      gradient flotation assay revealed that the membrane association of M1 was greatly
      affected in the absence of BM2, resulting in a decrease of vRNP in membrane
      fractions. These results strongly suggest that BM2 functions to capture the M1
      vRNP complex at the virion budding site during virus assembly.

PMID- 15452222
TI  - Anti-Vpr activity of a yeast chaperone protein.
AB  - Human immunodeficiency virus type 1 (HIV-1) viral protein R (Vpr) exerts multiple
      effects on viral and host cellular activities during viral infection, including
      nuclear transport of the proviral integration complex, induction of cell cycle
      G(2) arrest, and cell death. In this report, we show that a fission yeast
      chaperone protein Hsp16 inhibits HIV-1 by suppressing these Vpr activities. This
      protein was identified through three independent genome-wide screens for
      multicopy suppressors of each of the three Vpr activities. Consistent with the
      properties of a heat shock protein, heat shock-induced elevation or
      overproduction of Hsp16 suppressed Vpr activities through direct protein-protein
      interaction. Even though Hsp16 shows a stronger suppressive effect on Vpr in
      fission yeast than in mammalian cells, similar effects were also observed in
      human cells when fission yeast hsp16 was expressed either in vpr-expressing cells
      or during HIV-1 infection, indicating a possible highly conserved Vpr suppressing
      activity. Furthermore, stable expression of hsp16 prior to HIV-1 infection
      inhibits viral replication in a Vpr-dependent manner. Together, these data
      suggest that Hsp16 inhibits HIV-1 by suppressing Vpr-specific activities. This
      finding could potentially provide a new approach to studying the contribution of
      Vpr to viral pathogenesis and to reducing Vpr-mediated detrimental effects in HIV
      infected patients.

PMID- 15452223
TI  - Human cytomegalovirus infection induces rapamycin-insensitive phosphorylation of
      downstream effectors of mTOR kinase.
AB  - Signaling mediated by the cellular kinase mammalian target of rapamycin (mTOR)
      activates cap-dependent translation under normal (nonstressed) conditions.
      However, translation is inhibited by cellular stress responses or rapamycin
      treatment, which inhibit mTOR kinase activity. We show that during human
      cytomegalovirus (HCMV) infection, viral protein synthesis and virus production
      proceed relatively normally when mTOR kinase activity is inhibited due to hypoxic
      stress or rapamycin treatment. Using rapamycin inhibition of mTOR, we show that
      HCMV infection induces phosphorylation of two mTOR effectors, eucaryotic
      initiation factor 4E (eIF4E) binding protein (4E-BP) and eIF4G. The virally
      induced phosphorylation of eIF4G is both mTOR and phosphatidylinositol 3-kinase
      (PI3K) independent, whereas the phosphorylation of 4E-BP is mTOR independent, but
      PI3K dependent. HCMV infection does not induce mTOR-independent phosphorylation
      of a third mTOR effector, p70S6 kinase (p70S6K). We show that the HCMV-induced
      phosphorylation of eIF4G and 4E-BP correlates with the association of eIF4E, the
      cap binding protein, with eIF4G in the eIF4F translation initiation complex.
      Thus, HCMV induces mechanisms to maintain the integrity of the eIF4F complex even
      when mTOR signaling is inhibited.

PMID- 15452224
TI  - Caspase inhibition protects against reovirus-induced myocardial injury in vitro
      and in vivo.
AB  - Viral myocarditis is a disease with a high morbidity and mortality. The
      pathogenesis of this disease remains poorly characterized, with components of
      both direct virus-mediated and secondary inflammatory and immune responses
      contributing to disease. Apoptosis has increasingly been viewed as an important
      mechanism of myocardial injury in noninfectious models of cardiac disease,
      including ischemia and failure. Using a reovirus murine model of viral
      myocarditis, we characterized and targeted apoptosis as a key mechanism of virus
      associated myocardial injury in vitro and in vivo. We demonstrated caspase-3
      activation, in conjunction with terminal deoxynucleotidyltransferase-mediated
      dUTP-biotin nick end labeling and annexin binding, in cardiac myocytes after
      myocarditic viral infection in vitro. We also demonstrated a tight temporal and
      geographical correlation between caspase-3 activation, histologic injury, and
      viral load in cardiac tissue after myocarditic viral infection in vivo. Two
      pharmacologic agents that broadly inhibit caspase activity, Q-VD-OPH and Z
      VAD(OMe)-FMK, effectively inhibited virus-induced cellular death in vitro. The
      inhibition of caspase activity in vivo by the use of pharmacologic agents as well
      as genetic manipulation reduced virus-induced myocardial injury by 40 to 60% and
      dramatically improved survival in infected caspase-3-deficient animals. This
      study indicates that apoptosis plays a critical role in mediating cardiac injury
      in the setting of viral myocarditis and is the first demonstration that caspase
      inhibition may serve as a novel therapeutic strategy for this devastating
      disease.

PMID- 15452225
TI  - Identification of differentially expressed genes in scrapie-infected mouse brains
      by using global gene expression technology.
AB  - The pathogenesis of prion diseases, a class of transmissible fatal
      neurodegenerative diseases in humans and animals, is still unclear. The aim of
      this study was to identify the differentially regulated genes that correlate with
      the development of prion diseases for a better understanding of their
      pathological mechanisms. We employed Affymetrix Mouse Expression Arrays 430A
      containing >22,000 transcripts and compared the global gene expression profiles
      from brains of mice who were intracerebrally inoculated with scrapie strains ME7
      and RML with those from brains of uninfected and mock-infected mice. The
      microarray data were analyzed by Significance Analysis of Microarrays, revealing
      121 genes whose expression increased at least twofold in both ME7- and RML
      infected mouse brains, with an estimated false discovery rate of < or =5%. These
      genes encode proteins involved in proteolysis, protease inhibition, cell growth
      and maintenance, the immune response, signal transduction, cell adhesion, and
      molecular metabolism. The time course of expression generally showed up
      regulation of these genes from 120 days postinoculation (dpi) for ME7-inoculated
      mouse brains and from 90 dpi for RML-inoculated mouse brains. The onset of
      elevated expression correlated temporally with the onset of PrP(Sc) accumulation
      and the activation of glia, which may have contributed to neuronal cell death.
      Among the differentially regulated genes reported in the present study, the
      emergence of genes for several cathepsins and S100 calcium binding proteins was
      conspicuous. These and other genes reported here may represent novel potential
      diagnostic and therapeutic targets for prion disease.

PMID- 15452226
TI  - Structural and virological studies of the stages of virus replication that are
      affected by antirhinovirus compounds.
AB  - Pleconaril is a broad-spectrum antirhinovirus and antienterovirus compound that
      binds into a hydrophobic pocket within viral protein 1, stabilizing the capsid
      and resulting in the inhibition of cell attachment and RNA uncoating. When
      crystals of human rhinovirus 16 (HRV16) and HRV14 are incubated with pleconaril,
      drug occupancy in the binding pocket is lower than when pleconaril is introduced
      during assembly prior to crystallization. This effect is far more marked in HRV16
      than in HRV14 and is more marked with pleconaril than with other compounds. These
      observations are consistent with virus yield inhibition studies and radiolabeled
      drug binding studies showing that the antiviral effect of pleconaril against
      HRV16 is greater on the infectivity of progeny virions than the parent input
      viruses. These data suggest that drug integration into the binding pocket during
      assembly, or at some other late stage in virus replication, may contribute to the
      antiviral activity of capsid binding compounds.

PMID- 15452227
TI  - APOBEC3G genetic variants and their influence on the progression to AIDS.
AB  - The cytosine deaminase APOBEC3G, in the absence of the human immunodeficiency
      virus type 1 (HIV-1) accessory gene HIV-1 viral infectivity factor (vif),
      inhibits viral replication by introducing G-->A hypermutation in the newly
      synthesized HIV-1 DNA negative strand. We tested the hypothesis that genetic
      variants of APOBEC3G may modify HIV-1 transmission and disease progression.
      Single nucleotide polymorphisms were identified in the promoter region (three),
      introns (two), and exons (two). Genotypes were determined for 3,073 study
      participants enrolled in six HIV-AIDS prospective cohorts. One codon-changing
      variant, H186R in exon 4, was polymorphic in African Americans (AA) (f = 37%) and
      rare in European Americans (f < 3%) or Europeans (f = 5%). For AA, the variant
      allele 186R was strongly associated with decline in CD4 T cells (CD4 slope on
      square root scale: -1.86, P = 0.009), The 186R allele was also associated with
      accelerated progression to AIDS-defining conditions in AA. The in vitro antiviral
      activity of the 186R enzyme was not inferior to that of the common H186 variant.
      These studies suggest that there may be a modifying role of variants of APOBEC3G
      on HIV-1 disease progression that warrants further investigation.

PMID- 15452228
TI  - Repression of human T-cell leukemia virus type 1 and type 2 replication by a
      viral mRNA-encoded posttranscriptional regulator.
AB  - Human T-cell leukemia virus type 1 (HTLV-1) and HTLV-2 are complex retroviruses
      that persist in the host, eventually causing leukemia and neurological disease in
      a small percentage of infected individuals. In addition to structural and
      enzymatic proteins, HTLV encodes regulatory (Tax and Rex) and accessory (open
      reading frame I and II) proteins. The viral Tax and Rex proteins positively
      regulate virus production. Tax activates viral and cellular transcription to
      promote T-cell growth and, ultimately, malignant transformation. Rex acts
      posttranscriptionally to facilitate cytoplasmic expression of viral mRNAs that
      encode the structural and enzymatic gene products, thus positively controlling
      virion expression. Here, we report that both HTLV-1 and HTLV-2 have evolved
      accessory genes to encode proteins that act as negative regulators of both Tax
      and Rex. HTLV-1 p30(II) and the related HTLV-2 p28(II) inhibit virion production
      by binding to and retaining tax/rex mRNA in the nucleus. Reduction of viral
      replication in a cell carrying the provirus may allow escape from immune
      recognition in an infected individual. These data are consistent with the
      critical role of these proteins in viral persistence and pathogenesis in animal
      models of HTLV-1 and HTLV-2 infection.

PMID- 15452230
TI  - Molecular mechanisms of attenuation of the Sabin strain of poliovirus type 3.
AB  - Mutations critical for the central nervous system (CNS) attenuation of the Sabin
      vaccine strains of poliovirus (PV) are located within the viral internal ribosome
      entry site (IRES). We examined the interaction of the IRESs of PV type 3 (PV3)
      and Sabin type 3 (Sabin3) with polypyrimidine tract-binding protein (PTB) and a
      neural cell-specific homologue, nPTB. PTB and nPTB were found to bind to a site
      directly adjacent to the attenuating mutation, and binding at this site was less
      efficient on the Sabin3 IRES than on the PV3 IRES. Translation mediated by the
      PV3 and Sabin3 IRESs in neurons of the chicken embryo spinal cord demonstrated a
      translation deficit for the Sabin3 IRES that could be rescued by increasing PTB
      expression in the CNS. These data suggest that the low levels of PTB available in
      the CNS, coupled to a reduced binding of PTB on the Sabin3 IRES, leads to its CNS
      specific attenuation. This study also demonstrates the use of the chicken embryo
      to easily investigate translation of RNA within a neuron in the CNS of an intact
      living organism.

PMID- 15452229
TI  - Characterization of Nef-CXCR4 interactions important for apoptosis induction.
AB  - The HIV-1 Nef protein was analyzed for apoptotic structural motifs that interact
      with the CXCR4 receptor and induce apoptosis in CD4(+) lymphocytes. Two apoptotic
      motifs were identified. One centered on Nef amino acids (aa) 50 to 60, with the
      overlapping 20-mer peptides retaining about 82% of the activity of the full Nef
      protein. The second centered on aa 170 to 180, with the overlapping 20-mer
      peptides retaining about 30% of the activity of the full protein. Significant
      apoptotic abilities were observed for 11-mer motif peptides spanning aa 50 to 60
      and aa 170 to 180, with a scrambled version of the 11-mer motif peptide
      corresponding to aa 50 to 60 showing no apoptotic ability. Hallmarks of
      apoptosis, such as the formation of DNA ladders and caspase activation, that were
      observed with the full-length protein were equally evident upon exposure of cells
      to these motif peptides. A CXCR4 antibody and the endogenous ligand SDF-1alpha
      were effective in blocking Nef peptide-induced apoptosis as well as the physical
      binding of a fluorescently tagged Nef protein, while CCR5 antibodies were
      ineffective. The CXCR4-negative cell line MDA-MB-468 was resistant to the
      apoptotic peptides and became sensitive to the apoptotic peptides upon
      transfection with a CXCR4-expressing vector. A fluorescently tagged motif peptide
      and Nef protein displayed physical binding to CXCR4-transfected MDA-MB-468 cells,
      but not to CCR5-transfected cells. The removal of the apoptotic motif sequences
      from the full-length protein completely eliminated the ability of Nef to induce
      apoptosis. However, these modified Nef proteins still retained the ability to
      enhance viral infectivity. Thus, specific sequences in the Nef protein appear to
      be necessary for Nef protein-induced apoptosis as well as for physical
      interaction with CXCR4 receptors.

PMID- 15452231
TI  - Lytic replication-defective Kaposi's sarcoma-associated herpesvirus: potential
      role in infection and malignant transformation.
AB  - Defective viruses often have pivotal roles in virus-induced diseases. Although
      Kaposi's sarcoma-associated herpesvirus (KSHV) is etiologically associated with
      Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL), defective KSHV has not
      been reported. Using differential genetic screening methods, we show that
      defective KSHV is present in KS tumors and PEL cell lines. To investigate the
      role of defective viruses in KSHV-induced pathogenesis, we isolated and
      characterized a lytic replication-defective KSHV, KV-1, containing an 82-kb
      genomic deletion of solely lytic genes. Cells harboring KV-1 escaped G(0)/G(1)
      apoptosis induced by spontaneous lytic replication occurred in cells infected
      with regular KSHV but maintained efficient latent replication. Consequently, KV-1
      infected cells had phenotypes of enhanced cell proliferation and transformation
      potentials. Importantly, KV-1 was packaged as infectious virions by using regular
      KSHV as helpers, and KV-1-like variants were detected in cultures of two of five
      KSHV cell lines and 1 of 18 KS tumors. These results point to a potential role
      for defective viruses in the regulation of KSHV infection and malignant
      transformation.

PMID- 15452232
TI  - Disruption of Kaposi's sarcoma-associated herpesvirus latent nuclear antigen
      leads to abortive episome persistence.
AB  - Latent nuclear antigen (LNA) is implicated in Kaposi's sarcoma-associated
      herpesvirus (KSHV) episome persistence. LNA colocalizes with KSHV episomes on
      chromosomes in metaphase, and it maintains the stability and replication of KSHV
      terminal repeat-containing plasmids. In this study, we examined the function of
      LNA in episome persistence in the context of full-length KSHV genome by
      mutagenesis analysis. We generated a KSHV mutant, BAC36-DeltaLNA, with LNA
      disrupted by transposon-based mutagenesis with a KSHV BAC clone, BAC36, as a
      template. Immunofluorescence antibody staining revealed that the insertion of a
      transposon cassette into LNA disrupted its expression but had no effect on the
      expression of two adjacent genes, the vCyclin and vFLIP genes. Using a green
      fluorescent protein (GFP) cassette as a tracking marker for the KSHV episome, we
      found 8.7-fold-fewer GFP-positive cells in BAC36-DeltaLNA cultures than in wild
      type BAC36 cultures at the early stage following episome delivery into 293 cells
      by transfection, which could be partially rescued by cotransfection with a LNA
      expression plasmid but not a control plasmid. Cells harboring BAC36-DeltaLNA with
      or without transient complementation rapidly lost episomes and became virus-free
      after 2 weeks of culture based on GFP expression and Gardella gel analysis and
      quantitative PCR assays for detecting KSHV genomes. In contrast, BAC36 episomes
      were stably maintained during the same period. Stable cultures with close to 100%
      of cells harboring KSHV episomes were readily established by hygromycin selection
      for BAC36 but not for BAC36-DeltaLNA. These results conclusively indicate that
      LNA is essential for the establishment and persistence of KSHV episomes in
      mammalian cells.

PMID- 15452233
TI  - Relationships between infectious titer, capsid protein levels, and reverse
      transcriptase activities of diverse human immunodeficiency virus type 1 isolates.
AB  - Most studies on human immunodeficiency virus type 1 (HIV-1) replication kinetics
      or fitness must rely on a particular assay to initially standardize inocula from
      virus stocks. The most accurate measure of infectious HIV-1 titers involves a
      limiting dilution-infection assay and a calculation of the dose required for 50%
      infectivity of susceptible cells in tissue culture (TCID(50)). Surrogate assays
      are now commonly used to measure the amount of p24 capsid, the endogenous reverse
      transcriptase (RT) activity, or the amount of viral genomic RNA in virus
      particles. However, a direct comparison of these surrogate assays and actual
      infectious HIV-1 titers from TCID(50) assays has not been performed with even the
      most conserved laboratory strains, let alone the highly divergent primary HIV-1
      isolates of different subtypes. This study indicates that endogenous RT activity,
      not p24 content or viral RNA load, is the best surrogate measure of infectious
      HIV-1 titer in both cell-free supernatants and viruses purified on sucrose
      cushions. Sequence variation between HIV-1 subtypes did not appear to affect the
      function or activity of the RT enzyme in this endogenous assay but did affect the
      detection of p24 capsid by both enzyme immunoassays and Western blots. Clear
      groupings of non-syncytium-inducing (NSI), CCR5-tropic (R5), and SI/CXCR4-tropic
      (X4) HIV-1 isolates were observed when we compared the slopes derived from
      correlations of RT activity with infectious titers. Finally, the replication
      efficiency or fitness of both the NSI/R5 and SI/X4 HIV-1 isolates was not linked
      to the titers of the virus stocks.

PMID- 15452234
TI  - Avian reovirus temperature-sensitive mutant tsA12 has a lesion in major core
      protein sigmaA and is defective in assembly.
AB  - Members of our laboratory previously generated and described a set of avian
      reovirus (ARV) temperature-sensitive (ts) mutants and assigned 11 of them to 7 of
      the 10 expected recombination groups, named A through G (M. Patrick, R. Duncan,
      and K. M. Coombs, Virology 284:113-122, 2001). This report presents a more
      detailed analysis of two of these mutants (tsA12 and tsA146), which were
      previously assigned to recombination group A. The capacities of tsA12 and tsA146
      to replicate at a variety of temperatures were determined. Morphological analyses
      indicated that cells infected with tsA12 at a nonpermissive temperature produced
      approximately 100-fold fewer particles than cells infected at a permissive
      temperature and accumulated core particles. Cells infected with tsA146 at a
      nonpermissive temperature also produced approximately 100-fold fewer particles, a
      larger proportion of which were intact virions. We crossed tsA12 with ARV strain
      176 to generate reassortant clones and used them to map the temperature-sensitive
      lesion in tsA12 to the S2 gene. S2 encodes the major core protein sigmaA.
      Sequence analysis of the tsA12 S2 gene showed a single alteration, a cytosine-to
      uracil transition, at nucleotide position 488. This alteration leads to a
      predicted amino acid change from proline to leucine at amino acid position 158 in
      the sigmaA protein. An analysis of the core crystal structure of the closely
      related mammalian reovirus suggested that the Leu(158) substitution in ARV sigmaA
      lies directly under the outer face of the sigmaA protein. This may cause a
      perturbation in sigmaA such that outer capsid proteins are incapable of
      condensing onto nascent cores. Thus, the ARV tsA12 mutant represents a novel
      assembly-defective orthoreovirus clone that may prove useful for delineating
      virus assembly.

PMID- 15452235
TI  - Papillomavirus-like particles stimulate murine bone marrow-derived dendritic
      cells to produce alpha interferon and Th1 immune responses via MyD88.
AB  - Dendritic cells (DCs) link innate and adaptive immunity by sensing pathogens or
      vaccinogens and signaling a variety of defense responses. Since human
      papillomavirus type 16 L1 virus-like particles (HPV16 VLPs) induce a potent,
      protective immune response after vaccination, we examined their recognition by
      DCs. HPV16 VLPs cause phenotypic maturation of murine bone marrow-derived DCs
      (BMDCs), and immunization of mice with HPV16 VLP-loaded BMDCs or HPV16 VLPs alone
      induced T helper 1 (Th1)-biased immune responses. Analysis of transcriptional
      responses of murine BMDCs by microarray suggested that alpha/beta interferon (IFN
      alpha/beta) transcripts and numerous proinflammatory cytokines and chemokines are
      up regulated in response to HPV16 VLPs. Indeed, the induction of IFN-alpha, IFN
      gamma, and interleukin-12 (IL-12) production by BMDCs after stimulation with
      HPV16 VLPs was demonstrated by quantitative enzyme-linked immunosorbent assay.
      Many microbial products that induce proinflammatory responses are recognized via
      Toll-like receptor (TLR) signaling through the key adaptor protein MyD88 and
      activation of NF-kappaB, nuclear factor of activated T cells (NF-AT), and
      activating protein 1 (AP-1). Reporter assays indicated that HPV16 VLPs activated
      NF-kappaB-, NF-AT-, and AP-1-dependent transcription in the RAW264.7 macrophage
      cell line. Knockdown of MyD88 transcripts by small interfering RNA in the
      RAW264.7 macrophage cell line inhibited the activation of NF-kappaB-, NF-AT- and
      AP-1-dependent transcription by HPV16 VLP. Furthermore, MyD88(-/-) BMDCs failed
      to up regulate IL-12 and IFN-alpha and -gamma in response to HPV16 VLPs. Finally,
      Th1-biased immune responses to HPV16 VLPs are dramatically impaired in MyD88 and
      IFN-alpha/beta receptor-deficient mice. This implicates TLR recognition as
      central to immune recognition of HPV16 L1 VLPs.

PMID- 15452236
TI  - Interaction of the movement protein NSP and the Arabidopsis acetyltransferase
      AtNSI is necessary for Cabbage leaf curl geminivirus infection and pathogenicity.
AB  - DNA viruses can modulate the activity of cellular acetyltransferases to regulate
      virus gene expression and to affect cell cycle progression in order to support
      virus replication. A role for protein acetylation in regulating the nuclear
      export of the bipartite geminivirus DNA genome was recently suggested by the
      findings that the viral movement protein NSP, which shuttles the viral genome
      between the nucleus and the cytoplasm, interacts with a novel Arabidopsis
      acetyltransferase, AtNSI, and the increased expression of AtNSI enhances
      susceptibility to Cabbage leaf curl virus infection. To further investigate the
      interaction of NSP and AtNSI and to establish the importance of this interaction
      in virus infections, we used a reverse yeast two-hybrid selection and deletion
      analysis to identify NSP mutants that were impaired in their ability to bind
      AtNSI. These mutants identified a 38-amino-acid region of NSP, to which no
      function had so far been assigned, as being necessary for NSP-AtNSI interaction.
      Three NSP missense mutants were analyzed in detail and were found to be
      comparable to wild-type NSP in their levels of accumulation, nucleocytoplasmic
      shuttling, DNA binding, and cooperative interaction with the viral cell-to-cell
      movement protein MP. Despite this, Cabbage leaf curl virus that expressed each
      mutated NSP was defective in its ability to infect Arabidopsis, exhibiting lower
      levels of infectivity than the wild-type virus, and delayed systemic spread of
      the virus and attenuated disease symptoms. Our data demonstrate the importance of
      the interaction of NSP with AtNSI for virus infection and pathogenicity.

PMID- 15452237
TI  - Clonal selection for transcriptionally active viral oncogenes during progression
      to cancer.
AB  - Primary keratinocytes immortalized by human papillomaviruses (HPVs), along with
      HPV-induced cervical carcinoma cell lines, are excellent models for investigating
      neoplastic progression to cancer. By simultaneously visualizing viral DNA and
      nascent viral transcripts in interphase nuclei, we demonstrated for the first
      time a selection for a single dominant papillomavirus transcription center or
      domain (PVTD) independent of integrated viral DNA copy numbers or loci. The PVTD
      did not associate with several known subnuclear addresses but was almost always
      perinucleolar. Silent copies of the viral genome were activated by growth in the
      DNA methylation inhibitor 5-azacytidine. HPV-immortalized keratinocytes
      supertransduced with HPV oncogenes and selected for marker gene coexpression
      underwent crisis, and the surviving cells transcribed only the newly introduced
      genes. Thus, transcriptional selection in response to environmental changes is a
      dynamic process to achieve optimal gene expression for cell survival. This
      phenomenon may be critical in clonal selection during carcinogenesis. Examination
      of HPV-associated cancers supports this hypothesis.

PMID- 15452238
TI  - Identification of proteins associated with murine cytomegalovirus virions.
AB  - Proteins associated with the murine cytomegalovirus (MCMV) viral particle were
      identified by a combined approach of proteomic and genomic methods. Purified MCMV
      virions were dissociated by complete denaturation and subjected to either
      separation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and in
      gel digestion or treated directly by in-solution tryptic digestion. Peptides were
      separated by nanoflow liquid chromatography and analyzed by tandem mass
      spectrometry (LC-MS/MS). The MS/MS spectra obtained were searched against a
      database of MCMV open reading frames (ORFs) predicted to be protein coding by an
      MCMV-specific version of the gene prediction algorithm GeneMarkS. We identified
      38 proteins from the capsid, tegument, glycoprotein, replication, and
      immunomodulatory protein families, as well as 20 genes of unknown function.
      Observed irregularities in coding potential suggested possible sequence errors in
      the 3'-proximal ends of m20 and M31. These errors were experimentally confirmed
      by sequencing analysis. The MS data further indicated the presence of peptides
      derived from the unannotated ORFs ORF(c225441-226898) (m166.5) and ORF(105932
      106072). Immunoblot experiments confirmed expression of m166.5 during viral
      infection.

PMID- 15452239
TI  - Parainfluenza virus type 3 expressing the native or soluble fusion (F) Protein of
      Respiratory Syncytial Virus (RSV) confers protection from RSV infection in
      African green monkeys.
AB  - Respiratory syncytial virus (RSV) causes respiratory disease in young children,
      the elderly, and immunocompromised individuals, often resulting in
      hospitalization and/or death. After more than 40 years of research, a Food and
      Drug Administration-approved vaccine for RSV is still not available. In this
      study, a chimeric bovine/human (b/h) parainfluenza virus type 3 (PIV3) expressing
      the human PIV3 (hPIV3) fusion (F) and hemagglutinin-neuraminidase (HN) proteins
      from an otherwise bovine PIV3 (bPIV3) genome was employed as a vector for RSV
      antigen expression with the aim of generating novel RSV vaccines. b/h PIV3
      vaccine candidates expressing native or soluble RSV F proteins were evaluated for
      efficacy and immunogenicity in a nonhuman primate model. b/h PIV3 is suited for
      development of pediatric vaccines since bPIV3 had already been evaluated in
      clinical studies in 1- and 2-month-old infants and was found to be safe,
      immunogenic, and nontransmissible in a day care setting (Karron et al., Pediatr.
      Infect. Dis. J. 15:650-654, 1996; Lee et al., J. Infect. Dis. 184:909-913, 2001).
      African green monkeys immunized with b/h PIV3 expressing either the native or
      soluble RSV F protein were protected from challenge with wild-type RSV and
      produced RSV neutralizing and RSV F-protein specific immunoglobulin G serum
      antibodies. The PIV3-vectored RSV vaccines evaluated here further underscore the
      utility of this vector system for developing safe and immunogenic pediatric
      respiratory virus vaccines.

PMID- 15452240
TI  - Multiple V1/V2 env variants are frequently present during primary infection with
      human immunodeficiency virus type 1.
AB  - Human immunodeficiency virus type 1 (HIV-1) exists as a complex population of
      multiple genotypic variants in persons with chronic infection. However, acute HIV
      1 infection via sexual transmission is a low-probability event in which there is
      thought to be low genetic complexity in the initial inoculum. In order to assess
      the viral complexity present during primary HIV-1 infection, the V1/V2 and V3
      variable regions of the env gene were examined by using a heteroduplex tracking
      assay (HTA) capable of resolving these genotypic variants. Blood plasma samples
      from 26 primary HIV-1-infected subjects were analyzed for their level of
      diversity. Half of the subjects had more than one V1/V2 viral variant during
      primary infection, indicating the frequent transmission of multiple variants.
      This observation is inconsistent with the idea of infrequent transmission based
      on a small transmitting inoculum of cell-free virus. In chronically infected
      subjects, the complexity of the viral populations was even greater in both the
      V1/V2 and the V3 regions than in acutely infected subjects, indicating that in
      spite of the presence of multiple variants in acute infection, the virus does
      pass through a genetic bottleneck during transmission. We also examined how well
      the infecting virus penetrated different anatomical compartments by using the
      HTA. Viral variants detected in blood plasma were compared to those detected in
      seminal plasma and/or cerebral spinal fluid of six individuals. The virus in each
      of these compartments was to a large extent identical to virus in blood plasma, a
      finding consistent with rapid penetration of the infecting variant(s). The low
      probability transmission of multiple variants could be the result of transient
      periods of hyperinfectiousness or hypersusceptibility. Alternatively, the
      inefficient transfer of a multiply infected cell could account for both the low
      probability of transmission and the transfer of multiple variants.

PMID- 15452241
TI  - Cyclin-dependent kinase activity is required at early times for accurate
      processing and accumulation of the human cytomegalovirus UL122-123 and UL37
      immediate-early transcripts and at later times for virus production.
AB  - Human cytomegalovirus (HCMV) infection leads to dysregulation of multiple cell
      cycle-regulatory proteins. In this study, we examined the effects of inhibition
      of cyclin-dependent kinase (cdk) activity on viral replication. With the drug
      Roscovitine, a specific inhibitor of cyclin-dependent kinases 1, 2, 5, 7, and 9,
      we have shown that during the first 6 h of infection, cyclin-dependent kinase
      dependent events occurred that included the regulated processing and accumulation
      of the immediate-early (IE) UL122-123 transcripts and UL36-37 transcripts.
      Altered processing of UL122-123 led to a loss of IE1-72 and an increase in IE2
      86. The ratio of spliced to unspliced UL37 transcripts also changed. These
      effects did not require de novo protein synthesis or degradation of proteins by
      the proteasome. Addition of Roscovitine at the beginning of the infection was
      also associated with inhibition of expression of selected viral early gene
      products, viral DNA replication, and late viral gene expression. When Roscovitine
      was added after the first 6 h of infection, the effects on IE gene expression
      were no longer observed and viral replication proceeded through the late phase,
      but viral titers were reduced. The reduction in viral titer was observed even
      when Roscovitine was first added at 48 h postinfection, indicating that cyclin
      dependent kinase activity is required at both IE and late times. Flavopiridol,
      another specific inhibitor of cyclin-dependent kinases, had similar effects on IE
      and early gene expression. These results underscore the importance of accurate
      RNA processing and reiterate the significant role of cell cycle-regulatory
      factors in HCMV infection.

PMID- 15452242
TI  - Multiple epitopes in the murine cytomegalovirus early gene product M84 are
      efficiently presented in infected primary macrophages and contribute to strong
      CD8+-T-lymphocyte responses and protection following DNA immunization.
AB  - We previously demonstrated that after vaccination of BALB/c mice with DNA
      encoding murine cytomegalovirus (MCMV) IE1 or M84, a similar level of protection
      against MCMV infection was achieved. However, the percentage of antigen-specific
      CD8(+) T cells elicited by IE1 was higher than that by M84 as measured by
      intracellular cytokine staining when splenocytes were stimulated with an epitope
      peptide (M. Ye at al., J. Virol. 76:2100-2112, 2002). We show here that after DNA
      vaccination with M84, a higher percentage of M84-specific CD8(+) T cells was
      detected when splenocytes were stimulated with J774 cells expressing full-length
      M84. When the defined M84 epitope 297-305 was deleted, the mutant DNA vaccine was
      still protective against MCMV replication and induced strong M84-specific CD8(+)
      T-cell responses. The M84 gene was subsequently subcloned into three fragments
      encoding overlapping protein fragments. When mice were immunized with each of the
      M84 subfragment DNAs, at least two additional protective CD8(+)-T-cell epitopes
      were detected. In contrast to strong responses after DNA vaccination, M84
      specific CD8(+)-T-cell responses were poorly induced during MCMV infection. The
      weak M84-specific response after MCMV infection was not due to poor antigen
      presentation in antigen-presenting cells, since both J774 macrophages and primary
      peritoneal macrophages infected with MCMV in vitro were able to efficiently and
      constitutively present M84-specific epitopes starting at the early phase of
      infection. These results indicate that antigen presentation by macrophages is not
      sufficient for M84-specific CD8(+)-T-cell responses during MCMV infection.

PMID- 15452243
TI  - Antioxidant treatment reduces expansion and contraction of antigen-specific CD8+
      T cells during primary but not secondary viral infection.
AB  - During many viral infections, antigen-specific CD8(+) T cells undergo large-scale
      expansion. After viral clearance, the vast majority of effector CD8(+) T cells
      undergo apoptosis. Previous studies have implicated reactive oxygen intermediates
      (ROI) in lymphocyte apoptosis. The purpose of the experiments presented here was
      to determine the role of ROI in the expansion and contraction of CD8(+) T cells
      in vivo during a physiological response such as viral infection. Mice were
      infected with lymphocytic choriomeningitis virus (LCMV) and treated with
      Mn(III)tetrakis(4-benzoic acid)porphyrin chloride (MnTBAP), a metalloporphyrin
      mimetic compound with superoxide dismutase activity, from days 0 to 8
      postinfection. At the peak of CD8(+)-T-cell response, on day 8 postinfection, the
      numbers of antigen-specific cells were 10-fold lower in MnTBAP-treated mice than
      in control mice. From days 8 to 30, a contraction phase ensued where the numbers
      of antigen-specific CD8(+) T cells declined 25-fold in vehicle-treated mice
      compared to a 3.5-fold decrease in MnTBAP-treated mice. Differences in
      contraction appeared to be due to greater proliferation in drug-treated mice. By
      day 38, the numbers of antigen-specific CD8(+) memory T cells were equivalent for
      the two groups. The administration of MnTBAP during secondary viral infection had
      no effect on the expansion of antigen-specific CD8(+) secondary effector T cells.
      These data suggest that ROI production is critical for the massive expansion and
      contraction of antigen-specific CD8(+) T cells during primary, but not secondary,
      viral infection.

PMID- 15452244
TI  - Cytotoxic T-lymphocyte antigen 4 gene and recovery from hepatitis B virus
      infection.
AB  - Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is an inhibitory T-cell receptor
      expressed by activated and regulatory T cells. We hypothesized that single
      nucleotide polymorphisms (SNPs) in the gene encoding CTLA-4 may affect the vigor
      of the T-cell response to hepatitis B virus (HBV) infection, thus influencing
      viral persistence. To test this hypothesis, we genotyped six CTLA4 SNPs, from
      which all frequent haplotypes can be determined, using a large, matched panel of
      subjects with known HBV outcomes. Haplotypes with these SNPs were constructed for
      each subject using PHASE software. The haplotype distribution differed between
      those with viral persistence and those with clearance. Two haplotypes were
      associated with clearance of HBV infection, which was most likely due to
      associations with the SNPs -1722C (odds ratio [OR] = 0.60, P = 0.06) and +49G (OR
      = 0.73, P = 0.02). The wild-type haplotype, which contains an SNP leading to a
      decreased T-cell response (+6230A), was associated with viral persistence (OR =
      1.32, P = 0.04). These data suggest that CTLA4 influences recovery from HBV
      infection, which is consistent with the emerging role of T regulatory cells in
      the pathogenesis of disease.

PMID- 15452245
TI  - Evidence for gene expression by unintegrated human immunodeficiency virus type 1
      DNA species.
AB  - The integrated form of human immunodeficiency virus type 1 (HIV-1) DNA is
      classically considered to be the sole template for viral gene expression.
      However, several studies have suggested that unintegrated viral DNA species could
      also support transcription. To determine the contribution of the different
      species of HIV-1 DNA to viral expression, we first monitored intracellular levels
      of various HIV-1 DNA and RNA species in a single-round infection assay. We
      observed that, in comparison to the precocity of HIV-1 DNA synthesis, viral
      expression was delayed, suggesting that only the HIV-1 DNA species that persist
      for a sufficient period of time would be transcribed efficiently. We next
      evaluated the transcriptional activity of the circular forms of HIV-1 DNA bearing
      two long terminal repeats, since these episomes were reported to exhibit an
      intrinsic molecular stability. Our results support the notion that these circular
      species of HIV-1 DNA are naturally transcribed during HIV-1 infection, thereby
      participating in virus replication.

PMID- 15452246
TI  - Rapid human immunodeficiency virus decay in highly active antiretroviral therapy
      (HAART)-experienced children after starting mega-HAART.
AB  - Increasing numbers of patients are treated with mega-highly active antiretroviral
      therapy (HAART), or multiple-combination antiretroviral therapy, in an attempt to
      overcome the viral resistance that has contributed to treatment failure. Studies
      of human immunodeficiency virus (HIV) viral dynamics are used to quantify the
      potency of a given regimen. While mega-HAART is expected to provide potent
      therapy, its potency among heavily experienced HIV-infected children who have
      failed previous treatment is untested. HIV dynamics studies performed in children
      have provided minimal information on viral dynamics during mega-HAART. The
      present study estimates first- and second-phase viral dynamics in six children on
      mega-HAART, following failure of combination therapy. The first phase of viral
      decay was rapid, relative to rates reported in previous pediatric studies (median
      delta = 0.778d(-1), range = 0.583 to 1.088, half-life 1 [t1(1/2)] = 0.894d),
      while the second phase revealed results similar to those of previous studies
      (median mu = 0.026d(-1), range = -0.005 to 0.206, t2(1/2) = 9.316d). This
      indicates that mega-HAART can provide potent therapy among heavily experienced
      pediatric patients.

PMID- 15452247
TI  - Diversity of human immunodeficiency virus type 1 subtype A and CRF03_AB protease
      in Eastern Europe: selection of the V77I variant and its rapid spread in
      injecting drug user populations.
AB  - To characterize polymorphisms of the subtype A protease in the former Soviet
      Union, proviral DNA samples were obtained, with informed consent, from 119 human
      immunodeficiency virus type 1 (HIV-1)-positive untreated injecting drug users
      (IDUs) from 16 regions. All individuals studied have never been treated with
      antiretroviral drugs. The isolates were defined as IDU-A (n = 115) and CRF03_AB
      (n = 4) by using gag/env HMA/sequencing. The pro region was analyzed by using
      sequencing and original HIV-ProteaseChip hybridization technology. The mean of
      pairwise nucleotide distance between 27 pro sequences (23 IDU-A and 4 CRF03_AB)
      was low (1.38 +/- 0.79; range, 0.00 to 3.23). All sequences contained no primary
      resistance mutations. However, 13 of 23 (56.5%) subtype A isolates bore the V77I
      substitution known as the secondary protease mutation. V77I was associated with
      two synonymous substitutions in triplets 31 and 78, suggesting that all V77I
      bearing viruses evolved from a single source in 1997. Hybridization analysis
      showed that 55 of 115 (47.8%) HIV-1 isolates contained V77I, but this variant was
      not found in any of 31 DNA samples taken from regions, where the HIV-1 epidemic
      among IDUs started earlier 1997, as well as in any of four CRF03_AB isolates. The
      results of analysis of 12 additional samples derived from epidemiologically
      linked subjects showed that in all four epidemiological clusters the genotype of
      the donor and the recipients was the same irrespective of the route of
      transmission. This finding demonstrates the transmission of the V77I mutant
      variant, which is spreading rapidly within the circulating viral pool in Russia
      and Kazakhstan. The continued molecular epidemiological and virological
      monitoring of HIV-1 worldwide thus remains of great importance.

PMID- 15452248
TI  - A nucleotide binding motif in hepatitis C virus (HCV) NS4B mediates HCV RNA
      replication.
AB  - Hepatitis C virus (HCV) is a major cause of viral hepatitis. There is no
      effective therapy for most patients. We have identified a nucleotide binding
      motif (NBM) in one of the virus's nonstructural proteins, NS4B. This structural
      motif binds and hydrolyzes GTP and is conserved across HCV isolates. Genetically
      disrupting the NBM impairs GTP binding and hydrolysis and dramatically inhibits
      HCV RNA replication. These results have exciting implications for the HCV life
      cycle and novel antiviral strategies.

PMID- 15452249
TI  - Evolution of human immunodeficiency virus type 1 coreceptor usage during
      antiretroviral Therapy: a Bayesian approach.
AB  - There is substantial evidence for ongoing replication and evolution of human
      immunodeficiency virus type 1 (HIV-1), even in individuals receiving highly
      active antiretroviral therapy. Viral evolution in the presence of antiviral
      therapy needs to be considered when developing new therapeutic strategies.
      Phylogenetic analyses of HIV-1 sequences can be used for this purpose but may
      give rise to misleading results if rates of intrapatient evolution differ
      significantly. To improve analyses of HIV-1 evolution relevant to studies of
      pathogenesis and treatment, we developed a Bayesian hierarchical model that
      incorporates all available sequence data while simultaneously allowing the
      phylogenetic parameters of each patient to vary. We used this method to examine
      evolutionary changes in HIV-1 coreceptor usage in response to treatment. We
      examined patients whose viral populations exhibited a shift in coreceptor
      utilization in response to therapy. CXCR4 (X4) strains emerged in each patient
      but were suppressed following initiation of new antiretroviral regimens, so that
      CCR5-utilizing (R5) strains predominated. By phylogenetically reconstructing the
      evolutionary relationship of HIV-1 obtained longitudinally from each patient, it
      was possible to examine the origin of the reemergent R5 virus. Using our Bayesian
      hierarchical approach, we found that the reemergent R5 virus detectable after
      therapy was more closely related to the predecessor R5 virus than to the X4
      strains. The Bayesian hierarchical approach, unlike more traditional methods,
      makes it possible to evaluate competing hypotheses across patients. This model is
      not limited to analyses of HIV-1 but can be used to elucidate evolutionary
      processes for other organisms as well.

PMID- 15452250
TI  - Human immunodeficiency virus type 2 Gag interacts specifically with PRP4, a
      serine-threonine kinase, and inhibits phosphorylation of splicing factor SF2.
AB  - Using a yeast two-hybrid screen of a T-cell cDNA library to identify cellular
      proteins that bind to the human immunodeficiency virus type 2 (HIV-2) Gag
      polyprotein, we identified PRP4, a serine-threonine protein kinase. Specific
      interaction of PRP4 and HIV-2 Gag was confirmed in in vitro and in vivo assays.
      The interacting region of HIV-2 Gag is located in the conserved matrix and capsid
      domains, while both the RS (arginine-serine-rich) domain and the KS (kinase)
      domain of PRP4 are able to bind to HIV-2 Gag. PRP4 is not incorporated into virus
      particles. HIV-2 Gag is able to inhibit PRP4-mediated phosphorylation of the
      splicing factor SF2. This is also observed with Gag from simian immunodeficiency
      virus, a closely related virus, but not with Gag from human T-cell lymphotropic
      virus type 1. Our results provide evidence for a novel interaction between Gag
      and a cellular protein kinase involved in the control of constitutive splicing in
      two closely related retroviruses. We hypothesize that as Gag accumulates in the
      cell, down regulation of splicing occurs through reduced phosphorylation of SF2.
      At late stages of infection, this interaction may replace the function of the
      early viral regulatory protein Rev.

PMID- 15452251
TI  - Coxsackievirus B4-induced cytokine production in pancreatic cells is mediated
      through toll-like receptor 4.
AB  - Coxsackievirus B4 (CBV4), a member of the Picornavirus genus, has long been
      implicated in the development of insulin-dependent diabetes mellitus (IDDM)
      caused by virus-induced pancreatic cell damage. The progressive destruction of
      pancreatic beta cells is responsible for the development of IDDM. It has recently
      been suggested that CBV4 infection can induce the production of proinflammatory
      cytokines, and these cytokines seem to be involved in the damage to the insulin
      producing cells. In this study we investigated whether toll-like receptors (TLRs)
      are responsible for triggering the proinflammatory cytokine production in human
      pancreatic cells in response to CBV4. Here we demonstrate that CBV4 triggers
      cytokine production through a TLR4-dependent pathway. This interaction seems to
      be independent of virus attachment and cell entry.

PMID- 15452252
TI  - Protective efficacy of a DNA influenza virus vaccine is markedly increased by the
      coadministration of a Schiff base-forming drug.
AB  - Effective vaccination against heterologous influenza virus infection remains
      elusive. Immunization with plasmid DNA (pDNA) expressing conserved genes from
      influenza virus is a promising approach to achieve cross-variant protection.
      However, despite having been described for more than a decade, pDNA vaccination
      still requires further optimization to be applied clinically as a standard
      vaccination approach. We have recently described a simple and efficient approach
      to enhance pDNA immunization, based on the use of tucaresol, a Schiff base
      forming drug. In this report we have tested the ability of this drug to increase
      the protection conferred by pDNA vaccination against influenza virus infection.
      Our results demonstrate that a significant protection was achieved in two strains
      of mice by using the combination of pDNA and tucaresol. This protection was
      associated with an elevated humoral and cellular response and a switch in the
      type of the T helper cell (Th) immune response from type 2 to type 1. This
      vaccine combination represents a promising strategy for designing a clinical
      study for the protection from influenza and similar infections.

PMID- 15452253
TI  - Transient immunosuppression stops rejection of virus-transduced enhanced green
      fluorescent protein in rabbit retina.
AB  - The expression of lentivirus-transduced enhanced green fluorescent protein (EGFP)
      was detectable in rabbit retinal pigment epithelium (RPE) within 3 to 5 days
      after subretinal injection of the vector. Within 2 to 3 weeks, EGFP-expressing
      cells were eliminated by rejection. In the current experiments, we monitor serum
      antibody titers for EGFP before and after transduction and determine whether
      systemic immunosuppression prevents recognition of EGFP by the immune system.
      While all control rabbits developed antibodies against EFGP and showed signs of
      rejection, no such evidence was observed with animals which received
      immunosuppression. One month of systemic immunosuppression permanently prevented
      rejection of RPE with EGFP expression. Fluorescence has been maintained for more
      than a year. If a control eye was injected with the same virus after terminating
      immunosuppression, both eyes showed signs of rejection. The lack of rejection is
      not due to tolerance but to a failure of the animals to detect the foreign
      protein. Detection must depend upon a brief window of time after surgery needed
      to introduce the vector, perhaps related to a concurrent but transient
      inflammation. This strategy may be useful in managing other types of rejection in
      the retina.

PMID- 15452254
TI  - Small molecules blocking the entry of severe acute respiratory syndrome
      coronavirus into host cells.
AB  - Severe acute respiratory syndrome coronavirus (SARS-CoV) is the pathogen of SARS,
      which caused a global panic in 2003. We describe here the screening of Chinese
      herbal medicine-based, novel small molecules that bind avidly with the surface
      spike protein of SARS-CoV and thus can interfere with the entry of the virus to
      its host cells. We achieved this by using a two-step screening method consisting
      of frontal affinity chromatography-mass spectrometry coupled with a viral
      infection assay based on a human immunodeficiency virus (HIV)-luc/SARS
      pseudotyped virus. Two small molecules, tetra-O-galloyl-beta-D-glucose (TGG) and
      luteolin, were identified, whose anti-SARS-CoV activities were confirmed by using
      a wild-type SARS-CoV infection system. TGG exhibits prominent anti-SARS-CoV
      activity with a 50% effective concentration of 4.5 microM and a selective index
      of 240.0. The two-step screening method described here yielded several small
      molecules that can be used for developing new classes of anti-SARS-CoV drugs and
      is potentially useful for the high-throughput screening of drugs inhibiting the
      entry of HIV, hepatitis C virus, and other insidious viruses into their host
      cells.

PMID- 15452255
TI  - Predicting the impact of a nonsterilizing vaccine against human immunodeficiency
      virus.
AB  - Studies of human immunodeficiency virus (HIV) vaccines in animal models suggest
      that it is difficult to induce complete protection from infection (sterilizing
      immunity) but that it is possible to reduce the viral load and to slow or prevent
      disease progression following infection. We have developed an age-structured
      epidemiological model of the effects of a disease-modifying HIV vaccine that
      incorporates the intrahost dynamics of infection, a transmission rate and host
      mortality that depend on the viral load, the possible evolution and transmission
      of vaccine escape mutant viruses, a finite duration of vaccine protection, and
      possible changes in sexual behavior. Using this model, we investigated the long
      term outcome of a disease-modifying vaccine and utilized uncertainty analysis to
      quantify the effects of our lack of precise knowledge of various parameters. Our
      results suggest that the extent of viral load reduction in vaccinated infected
      individuals (compared to unvaccinated individuals) is the key predictor of
      vaccine efficacy. Reductions in viral load of about 1 log(10) copies ml(-1) would
      be sufficient to significantly reduce HIV-associated mortality in the first 20
      years after the introduction of vaccination. Changes in sexual risk behavior also
      had a strong impact on the epidemic outcome. The impact of vaccination is
      dependent on the population in which it is used, with disease-modifying vaccines
      predicted to have the most impact in areas of low prevalence and rapid epidemic
      growth. Surprisingly, the extent to which vaccination alters disease progression,
      the rate of generation of escape mutants, and the transmission of escape mutants
      are predicted to have only a weak impact on the epidemic outcome over the first
      25 years after the introduction of a vaccine.

PMID- 15452256
TI  - A lentiviral cDNA library employing lambda recombination used to clone an
      inhibitor of human immunodeficiency virus type 1-induced cell death.
AB  - Expression cloning technology of cDNAs is a suitable tool for identifying novel
      functional properties of genes. Here, we generated a lentiviral cDNA library
      expressing system for human T cells based on a site-specific recombination system
      of phage lambda for transferring cDNA libraries with a minimum loss of its
      complexity. The library-transduced CD4(+) T cells were challenged with wild-type
      human immunodeficiency virus type 1 (HIV-1), and the cells that acquired
      resistance to HIV-1-induced cytopathic effect (CPE) were selected. From these
      cells, CD14 was isolated and proved to inhibit the entry of HIV-1 and the HIV-1
      induced CPE. This cloning system allows rapid identification of genes encoding
      novel properties in human T cells and probably other mammalian cells.

PMID- 15452257
TI  - Genomic and proteomic analysis of thirty-nine structural proteins of shrimp white
      spot syndrome virus.
AB  - White spot syndrome virus (WSSV) virions were purified from the hemolymph of
      experimentally infected crayfish Procambarus clarkii, and their proteins were
      separated by 8 to 18% gradient sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE) to give a protein profile. The visible bands were then
      excised from the gel, and following trypsin digestion of the reduced and
      alkylated WSSV proteins in the bands, the peptide sequence of each fragment was
      determined by liquid chromatography-nano-electrospray ionization tandem mass
      spectrometry (LC-nanoESI-MS/MS) using a quadrupole/time-of-flight mass
      spectrometer. Comparison of the resulting peptide sequence data against the
      nonredundant database at the National Center for Biotechnology Information
      identified 33 WSSV structural genes, 20 of which are reported here for the first
      time. Since there were six other known WSSV structural proteins that could not be
      identified from the SDS-PAGE bands, there must therefore be a total of at least
      39 (33 + 6) WSSV structural protein genes. Only 61.5% of the WSSV structural
      genes have a polyadenylation signal, and preliminary analysis by 3' rapid
      amplification of cDNA ends suggested that some structural protein genes produced
      mRNA without a poly(A) tail. Microarray analysis showed that gene expression
      started at 2, 6, 8, 12, 18, 24, and 36 hpi for 7, 1, 4, 12, 9, 5, and 1 of the
      genes, respectively. Based on similarities in their time course expression
      patterns, a clustering algorithm was used to group the WSSV structural genes into
      four clusters. Genes that putatively had common or similar roles in the viral
      infection cycle tended to appear in the same cluster.

PMID- 15452258
TI  - Heterologous RNA encapsidated in Pariacoto virus-like particles forms a
      dodecahedral cage similar to genomic RNA in wild-type virions.
AB  - The genome of some icosahedral RNA viruses plays an essential role in capsid
      assembly and structure. In T=3 particles of the nodavirus Pariacoto virus (PaV),
      a remarkable 35% of the single-stranded RNA genome is icosahedrally ordered. This
      ordered RNA can be visualized at high resolution by X-ray crystallography as a
      dodecahedral cage consisting of 30 24-nucleotide A-form RNA duplex segments that
      each underlie a twofold icosahedral axis of the virus particle and interact
      extensively with the basic N-terminal region of 60 subunits of the capsid
      protein. To examine whether the PaV genome is a specific determinant of the RNA
      structure, we produced virus-like particles (VLPs) by expressing the wild-type
      capsid protein open reading frame from a recombinant baculovirus. VLPs produced
      by this system encapsidated similar total amounts of RNA as authentic virus
      particles, but only about 6% of this RNA was PaV specific, the rest being of
      cellular or baculovirus origin. Examination of the VLPs by electron
      cryomicroscopy and image reconstruction at 15.4-A resolution showed that the
      encapsidated RNA formed a dodecahedral cage similar to that of wild-type
      particles. These results demonstrate that the specific nucleotide sequence of the
      PaV genome is not required to form the dodecahedral cage of ordered RNA.

PMID- 15452259
TI  - Enhanced apoptosis of peripheral CD5-negative B lymphocytes from chronically
      hepatitis C virus-infected patients: reversal after antiviral treatment.
AB  - Whereas enhanced peripheral T-cell apoptosis and its association with
      autoimmunity have recently been reported, the apoptotic status of peripheral B
      cells in chronic hepatitis C virus (HCV) infection remains ambiguous. We
      therefore sought to investigate the sensitivity of peripheral B cells to
      apoptosis and to assess the possible benefits of antiviral treatment in
      mitigating these effects. Spontaneous apoptosis, the extent of apoptosis rescue,
      and NF-kappaB expression in peripheral B cells were studied in patients with
      chronic HCV infections (group 1), in sustained responders after antiviral
      treatment (group 2), and in healthy controls (group 3). For group 1, spontaneous
      B-cell apoptosis was increased (26% +/- 4.6%) and apoptosis rescue was altered
      (39%) compared to group 3 (18% +/- 5% and 50%, respectively; P = 0.001). In
      contrast, apoptosis and apoptosis rescue were similar for groups 2 and 3.
      Enhanced B-cell apoptosis was associated with decreased NF-kappaB expression and
      was found only in CD5-negative (CD5(neg)) B cells, whereas CD5(pos) cells were
      apoptosis resistant. Chronic HCV infection is associated with enhanced peripheral
      B-cell apoptosis and decreased apoptosis rescue. Successful antiviral treatment
      reverses these abnormalities to the levels seen in healthy individuals. The
      relative resistance of the CD5(pos) B-cell subpopulation to apoptosis may play a
      role in HCV-related autoimmunity and lymphoproliferation.

PMID- 15452260
TI  - Targeting c-Mpl for revival of human immunodeficiency virus type 1-induced
      hematopoietic inhibition when CD34+ progenitor cells are re-engrafted into a
      fresh stromal microenvironment in vivo.
AB  - The inhibition of multilineage hematopoiesis which occurs in the severe combined
      immunodeficiency mouse with transplanted human fetal thymus and liver tissues
      (SCID-hu Thy/Liv) due to human immunodeficiency virus type 1 (HIV-1) infection is
      also accompanied by a severe loss of c-Mpl expression on these progenitor cells.
      Inhibition of colony-forming activity (CFA) of the CD34(+) progenitor cells is
      partially revived to about 40% of mock-infected Thy/Liv implants, following
      reconstitution of the CD34(+) cells that were exposed to HIV-1 infection, in a
      new Thy/Liv stromal microenvironment of irradiated secondary SCID-hu recipients
      at 3 weeks post-re-engraftment. In addition, in these reconstituted animals, the
      proportion of c-Mpl(+) CD34(+) cells relative to c-Mpl(-) CD34(+) cells increased
      by about 25%, to 35% of mock-infected implants, suggesting a reacquirement of c
      Mpl phenotype by the c-Mpl(-) CD34(+) cells. These results suggest a correlation
      between c-Mpl expression and multilineage CFA of the human CD34(+) progenitor
      cells that have experienced the effects of HIV-1 infection. Treatment of the
      secondary-recipient animals with the c-Mpl ligand, thrombopoietin (Tpo), further
      increased c-Mpl expression and CFA of re-engrafted CD34(+) cells previously
      exposed to virus in the primary implants to about 50 to 70% over that of those re
      engrafted CD34(+) cells derived from implants of untreated animals. Blocking of c
      Mpl with anti-c-Mpl monoclonal antibody in vivo by injecting the SCID-hu animals
      resulted in the reduction or loss of CFA. Thus, inhibition, absence, or loss of c
      Mpl expression as in the c-Mpl(-) CD34(+) subset of cells is the likely cause of
      CFA inhibition. Further, CFA of the CD34(+) cells segregates with their c-Mpl
      expression. Therefore, c-Mpl may play a role in hematopoietic inhibition during
      HIV-1 infection, and control of its expression levels may aid in hematopoietic
      recovery and thereby reduce the incidence of cytopenias occurring in infected
      individuals.

PMID- 15452261
TI  - An N-terminal amphipathic helix in hepatitis C virus (HCV) NS4B mediates membrane
      association, correct localization of replication complex proteins, and HCV RNA
      replication.
AB  - Like other positive-strand RNA viruses, hepatitis C virus (HCV) is believed to
      replicate its RNA in association with host cell cytoplasmic membranes. Because of
      its association with such membranes, NS4B, one of the virus's nonstructural
      proteins, may play an important role in this process, although the mechanistic
      details are not well understood. We identified a putative N-terminal amphipathic
      helix (AH) in NS4B that mediates membrane association. Introduction of site
      directed mutations designed to disrupt the hydrophobic face of the AH abolishes
      the AH's ability to mediate membrane association. An AH in NS4B is conserved
      across HCV isolates. Completely disrupting the amphipathic nature of NS4B's N
      terminal helix abolished HCV RNA replication, whereas partial disruption resulted
      in an intermediate level of replication. Finally, immunofluorescence studies
      revealed that HCV replication complex components were mislocalized in the AH
      disrupted mutant. These results identify a key membrane-targeting domain which
      can form the basis for developing novel antiviral strategies.

PMID- 15452262
TI  - Macaque model for severe acute respiratory syndrome.
AB  - Rhesus and cynomolgus macaques were challenged with 10(7) PFU of a clinical
      isolate of the severe acute respiratory syndrome (SARS) coronavirus. Some of the
      animals developed a mild self-limited respiratory infection very different from
      that observed in humans with SARS. The macaque model as it currently exists will
      have limited utility in the study of SARS and the evaluation of therapies.

PMID- 15452263
TI  - Persistent infection with primate foamy virus type 1 increases human
      immunodeficiency virus type 1 cell binding via a Bet-independent mechanism.
AB  - We report that human T cells persistently infected with primate foamy virus type
      1 (PFV-1) display an increased capacity to bind human immunodeficiency virus type
      1 (HIV-1), resulting in increased cell permissiveness to HIV-1 infection and
      enhanced cell-to-cell virus transmission. This phenomenon is independent of HIV-1
      receptor, CD4, and it is not related to PFV-1 Bet protein expression. Increased
      virus attachment is specifically inhibited by heparin, indicating that it should
      be mediated by interactions with heparan sulfate glycosaminoglycans expressed on
      the target cells. Given that both viruses infect similar animal species, the
      issue of whether coinfection with primate foamy viruses interferes with the
      natural course of lentivirus infections in nonhuman primates should be
      considered.

PMID- 15452264
TI  - Visualization by live-cell microscopy of disruption of ND10 during herpes simplex
      virus type 1 infection.
AB  - ND10 structures are disrupted during herpes simplex virus type 1 (HSV-1)
      infection by viral regulatory protein ICP0. The significance of this effect
      remains controversial, partly because of a report that high-level expression of
      the major ND10 promyelocytic leukemia (PML) protein precludes ND10 disruption yet
      does not inhibit HSV-1 infection. Here we demonstrate dramatic reorganization of
      ND10 during HSV-1 infection by live-cell microscopy, even in the presence of
      overexpressed PML.

PMID- 15452265
TI  - Resolution of primary severe acute respiratory syndrome-associated coronavirus
      infection requires Stat1.
AB  - Intranasal inhalation of the severe acute respiratory syndrome coronavirus (SARS
      CoV) in the immunocompetent mouse strain 129SvEv resulted in infection of
      conducting airway epithelial cells followed by rapid clearance of virus from the
      lungs and the development of self-limited bronchiolitis. Animals resistant to the
      effects of interferons by virtue of a deficiency in Stat1 demonstrated a markedly
      different course following intranasal inhalation of SARS CoV, one characterized
      by replication of virus in lungs and progressively worsening pulmonary disease
      with inflammation of small airways and alveoli and systemic spread of the virus
      to livers and spleens.

PMID- 15452266
TI  - Thogoto virus lacking interferon-antagonistic protein ML is strongly attenuated
      in newborn Mx1-positive but not Mx1-negative mice.
AB  - The Thogoto virus ML protein suppresses interferon synthesis in infected cells.
      Nevertheless, a virus mutant lacking ML remained highly pathogenic in standard
      laboratory mice. It was strongly attenuated, however, in mice carrying the
      interferon-responsive Mx1 gene found in wild mice, demonstrating that enhanced
      interferon synthesis is protective only if appropriate antiviral effector
      molecules are present. Our study shows that the virulence-enhancing effects of
      some viral interferon antagonists may escape detection in conventional animal
      models.

PMID- 15452267
TI  - Modulation by morphine of viral set point in rhesus macaques infected with simian
      immunodeficiency virus and simian-human immunodeficiency virus.
AB  - Six rhesus macaques were adapted to morphine dependence by injecting three doses
      of morphine (5 mg/kg of body weight) for a total of 20 weeks. These animals along
      with six control macaques were infected intravenously with mixture of simian
      human immunodeficiency virus KU-1B (SHIV(KU-1B)), SHIV(89.6P), and simian
      immunodeficiency virus 17E-Fr. Levels of circulating CD4(+) T cells and viral
      loads in the plasma and the cerebrospinal fluid were monitored in these macaques
      for a period of 12 weeks. Both morphine and control groups showed precipitous
      loss of CD4(+) T cells. However this loss was more prominent in the morphine
      group at week 2 (P = 0.04). Again both morphine and control groups showed
      comparable peak plasma viral load at week 2, but the viral set points were higher
      in the morphine group than that in the control group. Likewise, the extent of
      virus replication in the cerebral compartment was more pronounced in the morphine
      group. These results provide a definitive evidence for a positive correlation
      between morphine and levels of viral replication.

PMID- 15452268
TI  - Efficient replication of severe acute respiratory syndrome coronavirus in mouse
      cells is limited by murine angiotensin-converting enzyme 2.
AB  - Replication of viruses in species other than their natural hosts is frequently
      limited by entry and postentry barriers. The coronavirus that causes severe acute
      respiratory syndrome (SARS-CoV) utilizes the receptor angiotensin-converting
      enzyme 2 (ACE2) to infect cells. Here we compare human, mouse, and rat ACE2
      molecules for their ability to serve as receptors for SARS-CoV. We found that,
      compared to human ACE2, murine ACE2 less efficiently bound the S1 domain of SARS
      CoV and supported less-efficient S protein-mediated infection. Rat ACE2 was even
      less efficient, at near background levels for both activities. Murine 3T3 cells
      expressing human ACE2 supported SARS-CoV replication, whereas replication was
      less than 10% as efficient in the same cells expressing murine ACE2. These data
      imply that a mouse transgenically expressing human ACE2 may be a useful animal
      model of SARS.

PMID- 15452269
TI  - Heterologous human immunodeficiency virus type 1 priming-boosting immunization
      strategies involving replication-defective adenovirus and poxvirus vaccine
      vectors.
AB  - We compared the human immunodeficiency virus type 1 (HIV-1)-specific cellular
      immune responses elicited in nonhuman primates by HIV-1 gag-expressing
      replication-defective adenovirus serotype 5 (Ad5) or poxvirus vectors, used
      either alone or in combination with each other. The responses arising from a
      heterologous Ad5 priming-poxvirus boosting regimen were significantly greater
      than those elicited by homologous regimens with the individual vectors or by a
      heterologous poxvirus priming-Ad5 boosting regimen. The heterologous Ad5 priming
      poxvirus boosting approach may have potential utility in humans as a means of
      inducing high levels of cellular immunity.

PMID- 15452270
TI  - Four EBNA2 domains are important for EBNALP coactivation.
AB  - EBNA2 transcriptional activation and regulated EBNALP coactivation are critical
      for Epstein-Barr virus-infected primary B-lymphocyte growth transformation.
      EBNALP coactivation requires the EBNA2 acidic activation domain (E2AD); EBNALP
      can bind to E2AD. EBNALP has now been found to bind less well to EBNA2 amino
      acids 1 to 58, which has been identified to be a second transcriptional
      activation domain, E2AD2. E2AD2 was specifically coactivated by EBNALP. Moreover,
      E2AD, E2AD2, EBNA2 RG domain, and the intermediate domain between RG and E2AD had
      significant roles in EBNA2-mediated activation and EBNALP coactivation.

PMID- 15452271
TI  - Myristoylation of the RING finger Z protein is essential for arenavirus budding.
AB  - The arenavirus small RING finger Z protein is the main driving force of
      arenavirus budding. The primary structure of Z is devoid of hydrophobic
      transmembrane domains, but both lymphocytic choriomeningitis virus (LCMV) and
      Lassa fever virus Z proteins accumulate near the inner surface of the plasma
      membrane and are strongly membrane associated. All known arenavirus Z proteins
      contain a glycine (G) at position 2, which is a potential acceptor site for a
      myristoyl moiety. Metabolic labeling showed incorporation of [(3)H]myristic acid
      by wild-type Z protein but not by the G2A mutant. The mutation G2A eliminated Z
      mediated budding. Likewise, treatment with the myristoylation inhibitor 2
      hydroxymyristic acid inhibited Z-mediated budding, eliminated formation of virus
      like particles, and caused a dramatic reduction in virus production in LCMV
      infected cells. Budding activity was restored in G2A mutant Z proteins by the
      addition of the myristoylation domain of the tyrosine protein kinase Src to their
      N termini. These findings indicate N-terminal myristoylation of Z plays a key
      role in arenavirus budding.

PMID- 15452272
TI  - Selection and evolution of NTP-specific aptamers.
AB  - ATP occupies a central position in biology, for it is both an elementary building
      block of RNA and the most widely used cofactor in all living organisms. For this
      reason, it has been a recurrent target for in vitro molecular evolution
      techniques. The exploration of ATP-binding motifs constitutes both an important
      step in investigating the plausibility of the 'RNA world' hypothesis and a
      central starting point for the development of new enzymes. To date, only two RNA
      motifs that bind ATP have been characterized. The first one is targeted to the
      adenosine moiety, while the second one recognizes the 'Hoogsteen' face of the
      base. To isolate aptamers that bind ATP in different orientations, we selected
      RNAs on an affinity resin that presents ATP in three different orientations. We
      obtained five new motifs that were characterized and subsequently submitted to a
      secondary selection protocol designed to isolate aptamers specific for
      cordycepin. Interestingly, all the ATP-binding motifs selected specifically
      recognize the sugar-phosphate backbone region of the nucleotides. Three of the
      aptamers show some selectivity for adenine derivatives, while the remainder
      recognize any of the four nucleotides with similar efficiency. The
      characteristics of these aptamers are discussed along with implications for in
      vitro molecular evolution.

PMID- 15452273
TI  - Pdr3 is required for DNA damage induction of MAG1 and DDI1 via a bi-directional
      promoter element.
AB  - In order to understand how gene regulation is achieved in eukaryotes in response
      to DNA damage, we used budding yeast as a model lower eukaryotic organism and
      investigated the molecular events leading to the expression of two closely
      clustered damage-inducible genes, MAG1 and DDI1. MAG1 and DDI1 are co-activated
      by a shared 8 bp repeat sequence, UAS(DM). In this study, we screened a yeast
      genomic library, identified Pdr3 as the transcriptional activator and
      demonstrated in vivo and in vitro that Pdr3 binds UAS(DM). Pdr3 is required for
      the activation of a number of genes encoding membrane efflux pumps and deletion
      of PDR3 results in reduced basal-level expression and loss of DNA damage
      induction of MAG1 and DDI1. Interestingly, Pdr1, another transcriptional
      activator homologous to Pdr3 that is also required for the activation of
      multidrug-resistance genes, is not involved in the regulation of MAG1 and DDI1
      expression, although it may also bind to UAS(DM). Deletion of PDR3 does not
      affect the expression of other well-documented DNA damage-inducible genes; hence,
      yeast DNA damage-inducible genes appear to have distinct effectors although to a
      certain extent they share a common regulatory pathway mediated by DNA damage
      checkpoints.

PMID- 15452274
TI  - A yeast arginine specific tRNA is a remnant aspartate acceptor.
AB  - High specificity in aminoacylation of transfer RNAs (tRNAs) with the help of
      their cognate aminoacyl-tRNA synthetases (aaRSs) is a guarantee for accurate
      genetic translation. Structural and mechanistic peculiarities between the
      different tRNA/aaRS couples, suggest that aminoacylation systems are unrelated.
      However, occurrence of tRNA mischarging by non-cognate aaRSs reflects the
      relationship between such systems. In Saccharomyces cerevisiae, functional links
      between arginylation and aspartylation systems have been reported. In particular,
      it was found that an in vitro transcribed tRNAAsp is a very efficient substrate
      for ArgRS. In this study, the relationship of arginine and aspartate systems is
      further explored, based on the discovery of a fourth isoacceptor in the yeast
      genome, tRNA4Arg. This tRNA has a sequence strikingly similar to that of tRNAAsp
      but distinct from those of the other three arginine isoacceptors. After
      transplantation of the full set of aspartate identity elements into the four
      arginine isoacceptors, tRNA4Arg gains the highest aspartylation efficiency.
      Moreover, it is possible to convert tRNA4Arg into an aspartate acceptor, as
      efficient as tRNAAsp, by only two point mutations, C38 and G73, despite the
      absence of the major anticodon aspartate identity elements. Thus, cryptic
      aspartate identity elements are embedded within tRNA4Arg. The latent aspartate
      acceptor capacity in a contemporary tRNAArg leads to the proposal of an
      evolutionary link between tRNA4Arg and tRNAAsp genes.

PMID- 15452275
TI  - DNA adopts normal B-form upon incorporation of highly fluorescent DNA base
      analogue tC: NMR structure and UV-Vis spectroscopy characterization.
AB  - The influence of the highly fluorescent tricyclic cytosine base analogue (tC) on
      duplex DNA conformation is investigated. The duplex properties are characterized
      by absorbance and circular dichroism (CD) for all combinations of neighbouring
      bases to tC, and an NMR structure is determined for one tC-containing sequence.
      For the oligonucleotides with one tC incorporated instead of cytosine, the
      melting temperature is increased on average by 2.7 degrees C above that for the
      unmodified ones. CD spectra are practically identical for modified and unmodified
      sequences, indicating an unperturbed B-DNA conformation. The NMR structure
      determination of the self-complementary sequence 5'-CTC(tC)ACGTGGAG shows a DNA
      conformation consistent with B-form for the whole duplex. The root-mean-square
      distance for the nucleotides of the eight central base pairs between the 10
      structures with lowest CYANA target functions and a mean structure is 0.45 +/-
      0.17 A. The NMR data confirm correct base pairing for tC by the observation of
      both intrastrand and interstrand imino proton NOEs. Altogether, this suggests
      that tC works well as a cytosine analogue, i.e. it is situated in the base stack,
      forming hydrogen bonds with G in the complementary strand, without distorting the
      DNA backbone conformation. This first example of an artificial, highly
      fluorescent DNA base that does not perturb the DNA conformation could have
      valuable applications for the study of the structure and dynamics of nucleic acid
      systems.

PMID- 15452276
TI  - Genome-wide analysis of alternative pre-mRNA splicing in Arabidopsis thaliana
      based on full-length cDNA sequences.
AB  - We mapped RIKEN Arabidopsis full-length (RAFL) cDNAs to the Arabidopsis thaliana
      genome to search for alternative splicing events. We used 278,734 full-length and
      3'/5' terminal reads of the sequences of 220,214 RAFL cDNA clones for the
      analysis. Eighty-nine percent of the cDNA sequences could be mapped to the genome
      and were clustered in 17,130 transcription units (TUs). Alternative splicing
      events were found in 1764 out of 15,214 TUs (11.6%) with multiple sequences. We
      collected full-length cDNA clones from plants grown under various environmental
      conditions or from various organs. We then analyzed the correlation between
      alternative splicing events and environmental stress conditions. Alternative
      splicing profiles changed according to environmental stress conditions and the
      various developmental stages of plant organs. In particular, cold-stress
      conditions affected alternative splicing profiles. The change in alternative
      splicing profiles under cold stress may be mediated by alternative splicing and
      transcriptional regulation of splicing factors.

PMID- 15452277
TI  - DNA polymerase beta overexpression stimulates the Rad51-dependent homologous
      recombination in mammalian cells.
AB  - Overexpression of DNA polymerase beta (polbeta), an error-prone DNA repair
      enzyme, has been shown to result in mutagenesis, aneuploidy and tumorigenesis. To
      further investigate the molecular basis leading to cancer-associated genetic
      changes, we examined whether the DNA polbeta could affect homologous
      recombination (HR). Using mammalian cells carrying an intrachromosomal
      recombination marker we showed that the DNA polbeta overexpression increased the
      HR mostly by enhancing gene conversion. Concomitantly, we observed the generation
      of DNA strand breaks as well as a DNA polbeta-dependent formation of Rad51 foci.
      The stimulation of HR was abolished by the coexpression of a dominant negative
      form of Rad51, suggesting that the Rad51 was involved in the increased HR events.
      The expression of different DNA polbeta mutants lacking polymerase activity did
      not result in HR stimulation, indicating that the DNA synthesis activity of DNA
      polbeta was related to this phenotype. These results provide new insights into
      the molecular mechanisms of the genetic instability observed in DNA polbeta
      overexpressing tumour cells.

PMID- 15452278
TI  - Method for direct discrimination of intra- and intermolecular hydrogen bonds, and
      characterization of the G(:A):G(:A):G(:A):G heptad, with scalar couplings across
      hydrogen bonds.
AB  - Discrimination of intra- and intermolecular hydrogen bonds in a symmetric
      multimer has not been accomplished yet, although such discrimination would
      provide a crucial basis for construction of the multimeric architecture of
      nucleic acids by NMR. We have developed a direct and unambiguous method for such
      discrimination involving the use of scalar couplings across hydrogen bonds. The
      method has been validated with a symmetric dimer of d(GGGCTTTTGGGC), for which
      the structure including both intra- and intermolecular hydrogen bonds was already
      reported. This has demonstrated that our method can clearly discriminate these
      two kinds of hydrogen bonds. Then, the method was applied to a symmetric dimer of
      d(GGAGGAGGAGGA) and has provided decisive information on its multimeric
      architecture. Additionally, the values for scalar couplings across hydrogen bonds
      for G:G and G:A base pairs in the G(:A):G(:A):G(:A):G heptad formed by
      d(GGAGGAGGAGGA) were determined for the first time. This determination has
      provided an insight into the nature of the heptad.

PMID- 15452279
TI  - A general role of the DNA glycosylase Nth1 in the abasic sites cleavage step of
      base excision repair in Schizosaccharomyces pombe.
AB  - One of the most frequent lesions formed in cellular DNA are abasic
      (apurinic/apyrimidinic, AP) sites that are both cytotoxic and mutagenic, and must
      be removed efficiently to maintain genetic stability. It is generally believed
      that the repair of AP sites is initiated by the AP endonucleases; however, an
      alternative pathway seems to prevail in Schizosaccharomyces pombe. A mutant
      lacking the DNA glycosylase/AP lyase Nth1 is very sensitive to the alkylating
      agent methyl methanesulfonate (MMS), suggesting a role for Nth1 in base excision
      repair (BER) of alkylation damage. Here, we have further evaluated the role of
      Nth1 and the second putative S.pombe AP endonuclease Apn2, in abasic site repair.
      The deletion of the apn2 open reading frame dramatically increased the
      sensitivity of the yeast cells to MMS, also demonstrating that the Apn2 has an
      important function in the BER pathway. The deletion of nth1 in the apn2 mutant
      strain partially relieves the MMS sensitivity of the apn2 single mutant,
      indicating that the Apn2 and Nth1 act in the same pathway for the repair of
      abasic sites. Analysis of the AP site cleavage in whole cell extracts of wild
      type and mutant strains showed that the AP lyase activity of Nth1 represents the
      major AP site incision activity in vitro. Assays with DNA substrates containing
      base lesions removed by monofunctional DNA glycosylases Udg and MutY showed that
      Nth1 will also cleave the abasic sites formed by these enzymes and thus act
      downstream of these enzymes in the BER pathway. We suggest that the main function
      of Apn2 in BER is to remove the resulting 3'-blocking termini following AP lyase
      cleavage by Nth1.

PMID- 15452280
TI  - The shape of things to come.

PMID- 15452281
TI  - Slippery slopes, wonder drugs, and cosmetic neurology: the neuroethics of
      enhancement.

PMID- 15452282
TI  - Pure autonomic failure: an immaculate misconception?

PMID- 15452283
TI  - Association of genetic loci: replication or not, that is the question.

PMID- 15452284
TI  - Practice parameter: treatment of postherpetic neuralgia: an evidence-based report
      of the Quality Standards Subcommittee of the American Academy of Neurology.
AB  - A systematic review of the literature on postherpetic neuralgia was performed.
      The authors identified studies using the National Library of Medicine's Medline
      database and Cochrane Library database. The authors determined absolute reduction
      rate, number needed to treat (NNT), 95% CI for NNT, and number needed to harm
      (NNH) for successful therapies of postherpetic neuralgia. Tricyclic
      antidepressants, gabapentin, pregabalin, opioids, and lidocaine patch were found
      to be effective in reducing the pain of postherpetic neuralgia.

PMID- 15452285
TI  - Cosmetic neurology: the controversy over enhancing movement, mentation, and mood.
AB  - Advances in cognitive neuroscience and neuropharmacology are yielding exciting
      treatments for neurologic diseases. Many of these treatments are also likely to
      have uses for people without disease. Here, I review the ways in which medicine
      might make bodies and brains function better by modulating motor, cognitive, and
      affective systems. These potential "quality of life" interventions raise ethical
      concerns, some related to the individual and others related to society. Despite
      these concerns, I argue that major restraints on the development of cosmetic
      neurology are not likely. Neurologists and other clinicians are likely to
      encounter patient-consumers who view physicians as gatekeepers in their own
      pursuit of happiness.

PMID- 15452286
TI  - Motor signs during the course of Alzheimer disease.
AB  - BACKGROUND: Motor signs (MOSIs) are common in Alzheimer disease (AD) and may be
      associated with rates of cognitive decline, mortality, and cost of care.
      OBJECTIVE: To describe the progression and identify predictors of individual
      MOSIs in AD. METHODS: A cohort of 474 patients with AD at early stages was
      followed semiannually for up to 13.1 years (mean 3.6 years) in five centers in
      Europe and the United States. MOSIs were rated using a standardized portion of
      the Unified Parkinson's Disease Rating Scale. Overall, 3,030 visits/assessments
      of MOSIs (average 6.4/patient) were performed. Prevalence and incidence rates
      were calculated, and cumulative risk graphs were plotted for individual non-drug
      induced MOSI domains. Rates of change over time taking into account potential
      covariates were also estimated. With use of each MOSI domain as outcome in Cox
      models, predictors of MOSI incidence were identified. RESULTS: At least one MOSI
      was detected in 13% of patients at first examination and in 36% for the last
      evaluation. Total MOSI score increased at an annual rate of 3% of total possible
      score. Rates of annual change for speech/facial expression (4%), rigidity
      (2.45%), posture/gait (3.9%), and bradykinesia (3.75%) were of similar magnitude,
      and their occurrence increased from first (3 to 6%) to last (22 to 29%)
      evaluation. Tremor was less frequent throughout the course of the disease (4% at
      first and 7% at last evaluation) and worsened less (0.75% increase/year).
      CONCLUSIONS: Most motor signs occur frequently and progress rapidly in Alzheimer
      disease. Tremor is an exception in that it occurs less frequently and advances at
      slower rates.

PMID- 15452287
TI  - NINDS AIREN neuroimaging criteria do not distinguish stroke patients with and
      without dementia.
AB  - OBJECTIVE: To determine the utility of the neuroimaging component within the
      National Institute of Neurological Disorders and Stroke (NINDS) Association
      Internationale pour la Recherche et l'Enseignement en Neurosciences (AIREN)
      criteria for vascular dementia for distinguishing between patients with and
      without dementia in the context of cerebrovascular disease. METHOD: One hundred
      twenty-five poststroke patients age > or =75 (27 with and 98 without poststroke
      dementia) from representative hospital-based stroke registers in the North East
      of England were evaluated using a 1.5 T MR scanner. The proportion of patients
      with and without poststroke dementia meeting the imaging component of the NINDS
      AIREN criteria was determined, and hippocampal atrophy (measured using the
      Schelten scale) was compared between the two groups. RESULTS: There were no
      significant differences between the patients with and without poststroke dementia
      on any criteria of the imaging parameters within the NINDS AIREN criteria. In
      addition, there were no significant differences in the number or size of cortical
      or subcortical infarcts between the two groups, with 13 patients without dementia
      having cortical infarcts >50 mm. Patients with dementia had greater hippocampal
      atrophy (right: Mann-Whitney U test, Z = 2.5, p = 0.01; left: Mann-Whitney U
      test, Z = 2.5, p = 0.01). CONCLUSION: The neuroimaging component of the NINDS
      AIREN criteria does not distinguish between older patients with and without
      poststroke dementia.

PMID- 15452288
TI  - In vivo evidence of cerebellar atrophy and cerebral white matter loss in
      Huntington disease.
AB  - OBJECTIVE: To investigate the regional pattern of white matter and cerebellar
      changes, as well as subcortical and cortical changes, in Huntington disease (HD)
      using morphometric analyses of structural MRI. METHODS: Fifteen individuals with
      HD and 22 controls were studied; groups were similar in age and education.
      Primary analyses defined six subcortical regions, the gray and white matter of
      primary cortical lobes and cerebellum, and abnormal signal in the cerebral white
      matter. RESULTS: As expected, basal ganglia and cerebral cortical gray matter
      volumes were significantly smaller in HD. The HD group also demonstrated
      significant cerebral white matter loss and an increase in the amount of abnormal
      signal in the white matter; occipital white matter appeared more affected than
      other cerebral white matter regions. Cortical gray and white matter measures were
      significantly related to caudate volume. Cerebellar gray and white matter volumes
      were both smaller in HD. CONCLUSIONS: The cerebellum and the integrity of
      cerebral white matter may play a more significant role in the symptomatology of
      HD than previously thought. Furthermore, changes in cortical gray and cerebral
      white matter were related to caudate atrophy, supporting a similar mechanism of
      degeneration.

PMID- 15452289
TI  - Diabetes mellitus and progression of rigidity and gait disturbance in older
      persons.
AB  - BACKGROUND: Parkinsonian-like signs, including rigidity, gait disturbance, and
      bradykinesia, are common and progressive in old age and are associated with
      morbidity and mortality. Few risk factors for these signs have been identified.
      Diabetes mellitus, also a common chronic condition in old age and known to be
      associated with physical and neurologic disability, may be associated with
      parkinsonian-like signs. OBJECTIVE: To examine the relation of diabetes to four
      parkinsonian-like signs. METHODS: Participants were 822 older Catholic clergymen
      and women who were without clinically diagnosed Parkinson disease or dementia at
      baseline. For up to 9 years, they had uniform annual evaluations, which included
      a modified version of the motor portion of the Unified Parkinson's Disease Rating
      Scale, from which previously established measures of four specific parkinsonian
      like signs were derived. Participants were evaluated for the presence of
      diabetes, based on direct medication inspection and history. RESULTS: Diabetes
      was present in 128 (15.6%) participants. In random effects models controlling for
      age, sex, and education, diabetes was associated with worsening rigidity (p <
      0.01) and gait (p < 0.05), over an average of 5.6 years of follow-up, but not
      with change in bradykinesia or tremor. The presence of stroke did not
      substantially affect the association of diabetes with rigidity but reduced the
      association of diabetes with gait to a trend (p = 0.08). CONCLUSION: Diabetes may
      be a previously unrecognized risk factor for progression of parkinsonian-like
      signs in older persons.

PMID- 15452290
TI  - Mortality in epilepsy: driving fatalities vs other causes of death in patients
      with epilepsy.
AB  - OBJECTIVES: To estimate the risk to public safety posed by drivers with epilepsy,
      the authors compared annual totals and disease-specific risk for fatal crashes
      associated with seizures and other medical conditions. They compared individual
      risks for fatal crashes due to seizures and other causes of mortality in patients
      with epilepsy. METHODS: The authors analyzed Multiple-Cause of Mortality data
      files from death certificates provided by the National Center for Health
      Statistics (NCHS) for the years 1995-97. They analyzed International
      Classification of Diseases-9 codes for underlying causes of death and other major
      conditions and determined disease-specific rates of fatal crashes associated with
      seizures and other medical conditions. RESULTS: An average of 44,027 US drivers
      died annually as a result of motor vehicle crashes during 1995-97; however, only
      86 (0.2%, range 82 to 97) of these deaths were associated with seizures in
      mortality reports. The incidence rate of fatal crashes for patients with seizures
      was 2.3 times the rate for patients with cardiovascular and hypertensive diseases
      and 4.6 times the rate for patients with diabetes. The proportionate mortality
      ratio for motor vehicle crashes in patients with seizures was low (0.2); most
      patients with epilepsy died of common cardiovascular and systemic disorders.
      CONCLUSION: Fatal driver crashes due to seizures are uncommon. This finding
      supports the current public policy of permitting patients whose seizures are
      controlled to drive.

PMID- 15452291
TI  - Depression and comorbidity in community-based patients with epilepsy or asthma.
AB  - OBJECTIVES: To assess the frequency of depression symptoms, quality of life, and
      disability in a community-based sample of epilepsy (EPI), asthma, and healthy
      control (NCH) subjects, and the relationship of depression with EPI-specific
      aspects of quality of life, social concerns, antiepileptic drug-related side
      effects, and employment. METHODS: Mail survey with depression (Center for
      Epidemiology Studies-Depression Scale [CES-D]), quality of life (Short Form [SF]
      36), and Sheehan Disability (SDS) scales to 775 EPI, 395 asthma, and 362 NCH
      subjects. EPI subjects completed Quality of Life in Epilepsy-89 (QOLIE-89),
      Social Concerns Index, Adverse Events Profile, and employment questions. RESULTS:
      A total of 36.5% EPI, 27.8% asthma, and 11.8% NCH were positive on CES-D (p <
      0.001). EPI had the most prior consultations and treatments for depression but
      38.5% of EPI-CES-D+ and 43.7% of asthma-CES-D+ were never previously evaluated
      for depression. EPI subjects had worse quality of life on SF-36 subscales and
      greater SDS disability but were similarly disabled as asthma subjects in the
      presence of depression. Among EPI subjects, CES-D-based depression was
      significantly associated with being female, being younger, lower income, worse
      QOLIE-89 scores, more SDS disability, more social concerns, more adverse drug
      events, less past-month employment, and fewer working days. CONCLUSIONS:
      Depression is common in community-based epilepsy and asthma patients, and is
      associated with diverse impairments.

PMID- 15452292
TI  - Ictal neocortical slowing in temporal lobe epilepsy.
AB  - BACKGROUND: Temporal lobe epilepsy (TLE) may affect brain regions outside the
      temporal lobe, causing impaired neocortical function during seizures. METHODS:
      The authors selected 11 consecutive patients with mesial TLE and hippocampal
      sclerosis who underwent intracranial EEG monitoring and had no seizures during a
      follow-up period of at least 1 year after temporal lobe resection. Secondarily
      generalized seizures were excluded, and up to three seizures were analyzed per
      patient (31 seizures total). Electrode contacts were assigned to one of nine
      cortical regions based on MRI surface reconstructions. EEG during seizures was
      analyzed for specific patterns including low-voltage fast (LVF), rhythmic
      polyspike, spike-wave, irregular slowing, and postictal suppression. RESULTS:
      Mesial and lateral temporal contacts on the side of seizure onset showed
      significant increases in ictal patterns such as LVF and polyspike activity,
      followed by postictal suppression. Bilateral frontal and ipsilateral parietal
      cortex exhibited large amplitude irregular slow waves during seizures. This
      frontoparietal slowing persisted into the postictal period. Perirolandic and
      occipital cortex were relatively spared. These EEG patterns were accompanied by
      bland staring, minor automatisms, and unresponsiveness or amnesia in the majority
      of patients studied. CONCLUSIONS: Prominent irregular slowing occurs in bilateral
      frontal and ipsilateral parietal association cortex during and after temporal
      lobe seizures. EEG slowing in the frontoparietal association cortex may signify
      physiologic impairment that contributes to widespread altered cerebral function
      during partial seizures.

PMID- 15452293
TI  - Correlating lamotrigine serum concentrations with tolerability in patients with
      epilepsy.
AB  - OBJECTIVE: To correlate lamotrigine (LTG) serum concentrations (levels) with
      tolerability in patients with epilepsy. METHODS: The charts of 811 outpatients
      with epilepsy who had received LTG and were seen at the Columbia Comprehensive
      Epilepsy Center after January 1, 2000, were reviewed. Data gathered included
      levels, dosage, duration of use, concomitant antiepileptic drugs (AEDs), clinical
      toxicity, specific side effects, and efficacy. Rates of toxicity, specific side
      effects, and efficacy were calculated and correlated with serum levels. RESULTS:
      In total, 3,731 LTG levels were recorded. A regimen was categorized as toxic if
      the patient experienced side effects that led to a dosage change or
      discontinuation of LTG. Of 3,919 AED regimens, 9.4% were toxic and 30.7% of
      patients had at least one toxic regimen. Toxicity increased with increasing LTG
      levels (p < 0.0001): With levels <5.0 microg/mL, 7% of patients were toxic; with
      levels of 5 to 10 microg/mL, 14%; with 10 to 15 microg/mL, 24%; with 15 to 20
      microg/mL, 34%; and with >20 microg/mL, 59%. The correlation between levels and
      tolerability was independent of concurrent medication. Increasing efficacy, as
      measured by seizure freedom for a 6-month period, occurred up to levels of >20
      microg/mL. CONCLUSIONS: There is a correlation between LTG serum level and
      tolerability, independent of the use of other AEDs. Adverse effects requiring a
      dose change are uncommon with the most frequently encountered LTG concentrations
      (<10 microg/mL) and occur in only 7.4% of patients at levels obtained during the
      majority of clinical trials (<5 microg/mL). An initial target range of 1.5 to 10
      microg/mL is suggested, though higher levels, up to >20 microg/mL, are often
      tolerated and can lead to additional efficacy in refractory patients.

PMID- 15452294
TI  - Status epilepticus after the initial diagnosis of epilepsy in children.
AB  - OBJECTIVES: To determine the risk and predictors of status epilepticus in
      children after they have been diagnosed with epilepsy. METHODS: In a prospective
      community-based cohort study of 613 children, the occurrence of status
      epilepticus after the initial diagnosis of epilepsy was ascertained. Parents were
      called every 3 months, and interval medical records were reviewed every 6 months.
      Predictors of primary interest included a history of status before the diagnosis
      of epilepsy, age at onset, underlying etiology, and epilepsy syndrome. Data were
      analyzed with chi2 tests, Kaplan-Meier analyses, and Cox proportional hazards
      models. RESULTS: Of 613 children followed a median of 8.0 years, 58 (9.5%) had >
      or =1 episode of status epilepticus during follow-up evaluation. The first
      episode occurred a median of 2.5 years after initial diagnosis (range, <1 month
      to 8.8 years). A history of previous status epilepticus was strongly associated
      with subsequent status epilepticus (18/56 [32.1%] vs 40/557 [7.2%]; p < 0.0001).
      Younger age at onset and symptomatic etiology contributed independently to the
      risk of status epilepticus. Mortality was higher in children with status
      epilepticus before diagnosis, largely secondary to underlying cause. CONCLUSIONS:
      Status epilepticus occurs in approximately 10% of children after initial
      diagnosis of epilepsy. Status epilepticus before initial diagnosis, young age at
      onset, and symptomatic etiology independently influence the risk of status
      epilepticus. In those without status epilepticus before diagnosis, the risk is
      modest and is realized over a prolonged period. For children at highest risk,
      maintaining abortive therapy in the home may be a reasonable precaution.

PMID- 15452295
TI  - Language cortex activation in normal children.
AB  - OBJECTIVE: To describe a protocol for use in young children and adolescents for
      determining language representation. METHODS: We performed 130 fMRI studies in 48
      children and 17 adults. Verb generation (VG) and orthographic lexical retrieval
      (OLR) were used. The localization and lateralization of activation was rated
      visually. Regional voxel counts measured asymmetry and extent of activation.
      RESULTS: Activation was predominantly left-lateralized (children 85%, adults
      94%), and there was no difference in the localization of activation for either
      paradigm. Children's typical sites of activation included mesial (96%), inferior
      (94%) and middle frontal (92%) gyri, the inferior (85%) and superior (65%)
      temporal cortex, and the cerebellum (67%). Less frequently activated sites were
      insular (50%) and posterior parietal (48%) cortices. Quantitative asymmetry index
      scores and visual inspection of laterality were concordant. Greater quantitative
      asymmetry for VG than OLR occurred in children. Laterality was not related to
      age, sex, task proficiency, or handedness. Frontal region voxel counts lower in
      children than adults and left sided counts correlated with task proficiency.
      CONCLUSIONS: Language fMRI can be performed in young children using resources
      available to clinical centers. The similarity in frequency of left language
      lateralization between children and adults suggests that language representation
      establishes early in development. The reduced amount of frontal region of
      interest activation in task-specific regions in children may reflect different
      levels of ability. However, the left-right distribution of activation does not
      appear to depend on task performance or age. These normative data provide a basis
      for decisions about language laterality in pediatric patients.

PMID- 15452296
TI  - ABILHAND-Kids: a measure of manual ability in children with cerebral palsy.
AB  - OBJECTIVE: To develop a clinical tool for measuring manual ability (ABILHAND
      Kids) in children with cerebral palsy (CP) using the Rasch measurement model.
      METHODS: The authors developed a 74-item questionnaire based on existing scales
      and experts' advice. The questionnaire was submitted to 113 children with CP (59%
      boys; mean age, 10 years) without major intellectual deficits (IQ > 60) and to
      their parents, and resubmitted to both groups after 1 month. The children's and
      parents' responses were analyzed separately with the WINSTEPS Rasch software to
      select items presenting an ordered rating scale, sharing the same discrimination,
      and fitting a unidimensional scale. RESULTS: The final ABILHAND-Kids scale
      consisted of 21 mostly bimanual items rated by the parents. The parents reported
      a finer perception of their children's ability than the children themselves,
      leading to a wider range of measurement, a higher reliability (R = 0.94), and a
      good reproducibility over time (R = 0.91). The item difficulty hierarchy was
      consistent between the parents and the experts. The ABILHAND-kids measures are
      significantly related to school education, type of CP, and gross motor function.
      CONCLUSIONS: ABILHAND-Kids is a functional scale specifically developed to
      measure manual ability in children with CP providing guidelines for goal setting
      in treatment planning. Its range and measurement precision are appropriate for
      clinical practice.

PMID- 15452297
TI  - Clinical and genetic heterogeneity of branching enzyme deficiency (glycogenosis
      type IV).
AB  - BACKGROUND: Glycogen storage disease type IV (GSD-IV) is a clinically
      heterogeneous autosomal recessive disorder due to glycogen branching enzyme (GBE)
      deficiency and resulting in the accumulation of an amylopectin-like
      polysaccharide. The typical presentation is liver disease of childhood,
      progressing to lethal cirrhosis. The neuromuscular form of GSD-IV varies in onset
      (perinatal, congenital, juvenile, or adult) and severity. OBJECTIVE: To identify
      the molecular bases of different neuromuscular forms of GSD-IV and to establish
      possible genotype/phenotype correlations. METHODS: Eight patients with GBE
      deficiency had different neuromuscular presentations: three had fetal akinesia
      deformation sequence (FADS), three had congenital myopathy, one had juvenile
      myopathy, and one had combined myopathic and hepatic features. In all patients,
      the promoter and the entire coding region of the GBE gene at the RNA and genomic
      level were sequenced. RESULTS: Nine novel mutations were identified, including
      nonsense, missense, deletion, insertion, and splice-junction mutations. The three
      cases with FADS were homozygous, whereas all other cases were compound
      heterozygotes. CONCLUSIONS: This study expands the spectrum of mutations in the
      GBE gene and confirms that the neuromuscular presentation of GSD-IV is clinically
      and genetically heterogeneous.

PMID- 15452298
TI  - Warfarin, hematoma expansion, and outcome of intracerebral hemorrhage.
AB  - BACKGROUND: Warfarin increases mortality of intracerebral hemorrhage (ICH). The
      authors investigated whether this effect reflects increased baseline ICH volume
      at presentation or increased ICH expansion. METHODS: Subjects were drawn from an
      ongoing prospective cohort study of ICH outcome. The effect of warfarin on
      baseline ICH volume was studied in 183 consecutive cases of supratentorial ICH
      age > or = 18 years admitted to the emergency department over a 5-year period.
      Baseline ICH volume was determined using computerized volumetric analysis. The
      effect of warfarin on ICH expansion (increase in volume > or = 33% of baseline)
      was analyzed in 70 consecutive cases in whom ICH volumes were measured on all
      subsequent CT scans up to 7 days after admission. Multivariable analysis was used
      to determine warfarin's influence on baseline ICH, ICH expansion, and whether
      warfarin's effect on ICH mortality was dependent on baseline volume or subsequent
      expansion. RESULTS: There was no effect of warfarin on initial volume. Predictors
      of larger baseline volume were hyperglycemia (p < 0.0001) and lobar hemorrhage (p
      < 0.0001). Warfarin patients were at increased risk of death, even when
      controlling for ICH volume at presentation. Warfarin was the sole predictor of
      expansion (OR 6.2, 95% CI 1.7 to 22.9) and expansion in warfarin patients was
      detected later in the hospital course compared with non-warfarin patients (p <
      0.001). ICH expansion showed a trend toward increased mortality (OR 3.5, 95% CI
      0.7 to 8.9, p = 0.14) and reduced the marginal effect of warfarin on ICH
      mortality. CONCLUSIONS: Warfarin did not increase ICH volume at presentation but
      did raise the risk of in-hospital hematoma expansion. This expansion appears to
      mediate part of warfarin's effect on ICH mortality.

PMID- 15452299
TI  - Restless legs syndrome and pregnancy.
AB  - OBJECTIVE: To perform a large and detailed epidemiologic study on restless legs
      syndrome (RLS) during pregnancy and the puerperium. METHODS: A structured
      clinical interview, assessing symptoms since the beginning of pregnancy, was
      performed to a population of 642 pregnant women at the time of delivery and at
      follow-up evaluation (1, 3, and 6 months after delivery). Main hematologic tests
      were also evaluated. A woman was considered affected if she met the International
      RLS Study Group criteria for RLS diagnosis. RESULTS: Twenty-six percent of women
      were affected by RLS during their pregnancy. The disease was strongly related to
      the third trimester of pregnancy and tended to disappear reaching the time of
      delivery. Affected women presented lower values of hemoglobin and mean
      corpuscular volume compared with healthy subjects (both groups received the same
      supplemental iron and folate therapy). CONCLUSIONS: Pregnancy is associated with
      transient restless legs syndrome.

PMID- 15452300
TI  - Clinical and laboratory assessment of distal peripheral nerves in Gulf War
      veterans and spouses.
AB  - BACKGROUND: The prevalence of symptoms suggesting distal symmetric polyneuropathy
      (DSP) was reported to be higher among deployed veterans (DV) to the Persian Gulf
      in 1990-1991 than to control non-deployed veterans (NDV). The authors therefore
      compared the prevalence of DSP by direct examination of DV and their spouses to
      control NDV and spouses. METHODS: The authors performed standardized neurologic
      examinations on 1,061 DV and 1,128 NDV selected from a cohort of veterans who
      previously participated in a national mail and telephone survey. Presence of DSP
      was evaluated by history, physical examination, and standardized
      electrophysiologic assessment of motor and sensory nerves. Similar examinations
      were performed without electrophysiologic tests in 484 DV spouses and 533 NDV
      spouses. Statistical analyses were performed with appropriate adjustments for the
      stratified sampling scheme. RESULTS: No differences between adjusted population
      prevalence of DSP in DV and NDV were found by electrophysiology (3.7% vs 6.3%, p
      = 0.07), by neurologic examination (3.1% vs 2.6%, p = 0.60), or by the methods
      combined (6.3% vs 7.3%, p = 0.47). Excluding veterans with non-military service
      related diseases that may cause DSP did not alter outcomes. DV potentially
      exposed to neurotoxins from the Khamisiyah ammunition depot explosion did not
      significantly differ in DSP prevalence compared to non-exposed DV. The prevalence
      of DSP in DV spouses did not differ from NDV spouses (2.7% vs 3.2%, p = 0.64).
      CONCLUSIONS: Neither veterans deployed during the Gulf War era nor their spouses
      had a higher prevalence of DSP compared to NDV and spouses.

PMID- 15452301
TI  - MRI in acute intermittent maple syrup urine disease.

PMID- 15452302
TI  - The bioavailability of IV methylprednisolone and oral prednisone in multiple
      sclerosis.
AB  - Oral prednisone (1)might be a convenient, inexpensive alternative to IV
      methylprednisolone (IVMP) if the bioequivalent dose was known. We compared the
      total amount of steroid absorbed after 1250 mg oral prednisone vs 1 gram IVMP in
      16 patients with multiple sclerosis (MS). At 24 hours, the mean area under the
      concentration-time curve (AUC), the main component of bioavailability, did not
      differ between groups (p = 0.122). This suggests that the amount of absorbed
      corticosteroid is similar after either steroid at these doses.

PMID- 15452303
TI  - Plasma exchange for severe optic neuritis: treatment of 10 patients.
AB  - The authors reviewed a series of 10 consecutive patients treated with plasma
      exchange (PE) for acute, severe optic neuritis (ON) largely unresponsive to
      previous high-dose IV glucocorticosteroids. PE was associated with an improvement
      of visual acuity according to the study criteria in 7 of 10 patients. On follow
      up, three of these patients continued to improve, two remained stable, and two
      had worsened again. PE may be beneficial as an escalating treatment in a subset
      of patients with severe ON. A controlled trial is warranted.

PMID- 15452304
TI  - Bias in parental transmission of the HLA-DR3 allele in Sardinian multiple
      sclerosis.
AB  - The authors analyzed the female: male (F:M) ratio according to the HLA-DRB1-DQB1
      genotype in a cohort of multiple sclerosis (MS) patients from Sardinia, where the
      disease is associated with DR3 and DR4. In the whole cohort of 1,097 patients,
      F:M ratio was 2.24; however, it was 2.88 in DR3/DR3 and 2.52 in DR3/DRX (X#DR3
      and DR4) individuals. Parental transmission of DR3 and DR4, assessed in a set of
      565 case-parent triads, showed evidence of paternal inheritance of DR3 in
      affected women, thus explaining the excess of females in the DR3 category.

PMID- 15452305
TI  - Association of an ABCB1 gene haplotype with pharmacoresistance in temporal lobe
      epilepsy.
AB  - The multidrug transporter P-glycoprotein is suspected of contributing to
      pharmacoresistance in temporal lobe epilepsy (TLE). To assess the role of
      functional variations in its coding gene (ABCB1) the authors genotyped 210
      patients with TLE who were stratified according to their degree of drug
      resistance. They identified a common haplotype that when present in the
      homozygous state significantly increased the risk for pharmacoresistance.

PMID- 15452306
TI  - Failure to confirm association of a polymorphism in ABCB1 with multidrug
      resistant epilepsy.
AB  - Alteration of ATP-binding cassette subfamily B member 1 transporter (ABCB1) can
      plausibly cause drug-resistant epilepsy as it influences brain penetration of
      drugs. The CC genotype at the ABCB1 C3435T polymorphism was reported to be
      associated with multidrug resistance. A replication study in 401 drug-resistant
      and 208 drug-responsive subjects with epilepsy showed no significant association
      between the CC genotype and drug-resistant epilepsy. The authors suggest the
      initial association may have arisen by chance.

PMID- 15452307
TI  - Autonomic failure as the initial presentation of Parkinson disease and dementia
      with Lewy bodies.
AB  - The authors report the clinical and postmortem neuropathologic findings of two
      patients, one with Parkinson disease (PD) and one with dementia with Lewy bodies
      (DLB), both of whom initially sought treatment for isolated autonomic failure.
      These cases suggest that neurodegeneration in PD and DLB may begin outside the
      CNS in autonomic postganglionic neurons, a finding with potential diagnostic and
      therapeutic implications.

PMID- 15452308
TI  - Glabellar and palmomental reflexes in Parkinsonian disorders.
AB  - The authors examined the glabellar reflex and the palmomental reflex in 100
      subjects, including patients with Parkinson disease (n = 41), patients with
      progressive supranuclear palsy (n = 12), patients with multiple system atrophy (n
      = 7), and healthy, age-matched, controls (n = 40). The study provides evidence
      that these reflexes, particularly glabellar reflex, are relatively sensitive
      signs of parkinsonian disorders, but they lack specificity as they do not
      differentiate among the three most common parkinsonian disorders.

PMID- 15452309
TI  - Acetaminophen in the treatment of headaches associated with dipyridamole-aspirin
      combination.
AB  - The authors assessed the prevalence of headaches following extended-release
      dipyridamole/aspirin combination (DAC), and the efficacy of acetaminophen in the
      treatment of these headaches. Following DAC, 38.7% of the participants developed
      headaches. The headaches were self-limited (69.4% placebo efficacy in 2 hours)
      and the incidence markedly declined over time. Acetaminophen was no more
      effective than placebo in the acute and preemptive treatment of these headaches.

PMID- 15452310
TI  - Hemorrhagic infarction in white matter following acute carbon monoxide poisoning.
AB  - Hemorrhage complicating acute carbon monoxide poisoning is usually confined to
      the basal ganglia. The authors report three people with acute carbon monoxide
      poisoning manifesting selective or prominent white matter involvement complicated
      by hemorrhagic infarction on CT and MRI in one and by subcortical T2*-weighted
      MRI abnormality in all three.

PMID- 15452311
TI  - ApoE epsilon4 allele is associated with incidental hallucinations and delusions
      in patients with AD.
AB  - Of 135 patients with Alzheimer disease (AD), 56 without psychiatric symptoms at
      the first visit were followed for a mean period of 51.9 +/- 10.3 months to
      identify incident psychiatric symptoms. The hazard ratios of ApoE epsilon4 allele
      in developing psychiatric symptoms were calculated by Cox regression hazard
      analyses. The presence of the ApoE epsilon4 allele carried a 19.0-fold risk for
      developing hallucinations and a 3.4-fold risk for delusions.

PMID- 15452312
TI  - Evidence of kinesin heavy chain (KIF5A) involvement in pure hereditary spastic
      paraplegia.
AB  - Hereditary spastic paraplegias (HSPs) are characterized by progressive lower
      extremity spasticity due to an axonal degeneration of motor and sensory neurons.
      We report a four-generation pedigree segregating an autosomal dominant phenotype
      for HSP and showing a linkage to the SPG10 locus, coding for Kinesin family
      member 5A. Subsequent to a denaturing high performance liquid chromatography
      (dHPLC) mutation screening we found a new missense mutation 838C>T (R280C) at an
      invariant arginine residue in a region involved in the microtubule binding
      activity.

PMID- 15452313
TI  - Familial myopathy with tubular aggregates associated with abnormal pupils.
AB  - The authors describe familial tubular aggregate myopathy associated with abnormal
      pupils. Four family members from two generations had myopathy and pupillary
      abnormalities. The myopathologic findings consisted of tubular aggregates in many
      fibers but predominantly type I fibers.

PMID- 15452314
TI  - Mutant ubiquitin UBB+1 is accumulated in sporadic inclusion-body myositis muscle
      fibers.
AB  - Mutant ubiquitin (UBB+1), a product of "molecular misreading," is toxic to cells
      because its ubiquitinated form inhibits the proteasome, contributing to
      accumulation of misfolded proteins and their ensuing toxicity. The authors
      demonstrate in 10 sporadic inclusion body myositis (s-IBM) muscle biopsies that
      UBB+1 is accumulated in aggregates containing amyloid-beta and phosphorylated
      tau. In s-IBM, UBB+1 may be pathogenic by inhibiting proteasome, thereby
      promoting accumulation of cytotoxic misfolded amyloid-beta and phosphorylated
      tau.

PMID- 15452315
TI  - LAMA2 loss-of-function mutation in a girl with a mild congenital muscular
      dystrophy.
AB  - The authors report a girl with autosomal recessive congenital muscular dystrophy
      linked to chromosome 6 (MDC1A) who carries a homozygous out-of-frame deletion in
      exon 56 of the LAMA2 gene but has a mild phenotype. She is still ambulant at age
      13 years, shows white matter abnormalities on MRI, and traces of laminin alpha2
      in her muscle biopsy with one of three antibodies used. This patient suggests
      that modulating factors can be associated with a less severe clinical phenotype
      in MDC1A.

PMID- 15452316
TI  - Spontaneous dissection of carotid and coronary arteries.
AB  - The authors report a case of spontaneous dissection of both carotid arteries,
      followed by spontaneous dissection of the left anterior descending coronary
      artery after a few days. No major abnormalities of collagen production were
      found. This case may be underlain by a dysplasia of common precursors of the
      carotid and coronary walls.

PMID- 15452317
TI  - Effectiveness of vagus nerve stimulation in epilepsy patients: a 12-year
      observation.
AB  - A retrospective review of the safety, tolerability, and efficacy of vagus nerve
      stimulation (VNS) in 48 patients with intractable partial epilepsy was performed.
      Side effects were few and mild to moderate. Mean seizure frequency decreased by
      26% after 1 year, 30% after 5 years, and 52% after 12 years with VNS treatment.

PMID- 15452318
TI  - Intracranial EEG study of seizure-associated nose wiping.
AB  - The authors studied the relation between seizure-associated nose wiping (NW) and
      intracerebral EEG data in 32 patients. NW was more frequent in mesial temporal
      lobe seizures (TLSs; 65%) than in other TLSs (36%; p < 0.05) and in frontal lobe
      seizures (3%; p < 0.0001). It was associated with the presence of an amygdala
      discharge at seizure onset (p < 0.05) and with the recording of an ictal low
      voltage fast activity within that structure (p < 0.05), supporting the role of an
      amygdala dysfunction in the pathophysiology of NW.

PMID- 15452319
TI  - Mogul-clonus.

PMID- 15452320
TI  - Hypertensive encephalopathy: BP lowering complicated by posterior circulation
      ischemic stroke.

PMID- 15452321
TI  - Tacrolimus leukoencephalopathy: a neuropathologic confirmation.

PMID- 15452322
TI  - Natural history of conservatively treated meningiomas.

PMID- 15452323
TI  - Gene-gene interaction between interleukin-6 and interleukin-10 reduces AD risk.

PMID- 15452324
TI  - Childhood epilepsy, familial hemiplegic migraine, cerebellar ataxia, and a new
      CACNA1A mutation.

PMID- 15452325
TI  - Sensory exam with a quantitative tuning fork: rapid, sensitive and predictive of
      SNAP amplitude.

PMID- 15452326
TI  - Treatment of autoimmune myasthenia gravis.

PMID- 15452327
TI  - Association of APOE polymorphisms with disease severity in MS is limited to
      women.

PMID- 15452328
TI  - The utility of MRI in suspected MS: report of the Therapeutics and Technology
      Assessment Subcommittee.

PMID- 15452329
TI  - Syndrome resembling PSP after surgical repair of ascending aorta dissection or
      aneurysm.

PMID- 15452330
TI  - Liver injury associated with the beta-interferons for MS.

PMID- 15452331
TI  - Patient page. The risk of fatal car crashes in people with epilepsy.

PMID- 15452332
TI  - High-throughput screening using label-free technologies.

PMID- 15452333
TI  - Cellular dielectric spectroscopy: a powerful new approach to label-free cellular
      analysis.
AB  - The past decade has seen a number of significant changes in identifying higher
      quality lead compounds earlier in the drug discovery process. Cell-based assay
      technologies yielding high-content information have emerged to achieve this goal.
      Although most of these systems are based on fluorescence detection, this article
      describes the development and application of an innovative cellular assay
      technology based on radio frequency spectrometry and bioimpedance measurements.
      Using this technique, the authors have discovered a link between cellular
      bioimpedance changes and receptor-mediated signal transduction events. By
      performing dielectric spectroscopy of cells across as pectrum of frequencies (1
      KHz to 110 MHz), a series of receptor-specific, frequency-dependent impedance
      patterns is collected. These raw data patterns are used to determine the identity
      of the cellular receptor-signaling pathway being tested and to quantify
      stimulation endpoints and kinetics. The authors describe the application of this
      technology to the analysis of ligand-induced cellular responses mediated by the 3
      major classes of G-protein-coupled receptors (GPCRs) and protein tyrosine kinase
      receptors. This single assay platform can be used with ease to monitor G(s),
      G(i), and G(q) GPCRs without the need for chimeric or promiscuous G-proteins,
      fluorophors, or tagged proteins. In contrast to other methods of monitoring
      cellular signal transduction, this approach provides high information content in
      a simplified, noninvasive, and biologically relevant fashion.

PMID- 15452334
TI  - Label-free assays on the BIND system.
AB  - Screening of biochemical interactions becomes simpler, less expensive, and more
      accurate when labels, such as fluorescent dyes, radioactive markers, and
      colorimetric reactions, are not required to quantify detected material. SRU
      Biosystems has developed a biosensor technology that is manufactured on
      continuous sheets of plastic film and incorporated into standard microplates and
      microarray slides to enable label-free assays to be performed with high
      throughput, high sensitivity, and low cost per assay. The biosensor incorporates
      a narrow band guided-mode resonance reflectance filter, in which the reflected
      color is modulated by the attachment/detachment of biochemical material to the
      surface. The technology offers 4 orders of linear dynamic range and uniformity
      within a plate, with a coefficient of variation of 2.5%. Using conventional
      biochemical immobilization surface chemistries, a wide range of assay
      applications are enabled. Small molecule screening, cell
      proliferation/cytotoxicity, enzyme activity screening, protein-protein
      interaction, and cell membrane receptor expression are among the applications
      demonstrated.

PMID- 15452335
TI  - Label-free protein and pathogen detection using the atomic force microscope.
AB  - The atomic force microscope (AFM) uses a sharp micron-scale tip to scan and
      amplify surface features, providing exceptionally detailed topographical
      information with magnification on the order of x10(6). This instrument is used
      extensively for quality control in the computer and semiconductor industries and
      is becoming a progressively more important tool in the biological sciences.
      Advantages of the AFM for biological application include the ability to obtain
      information in a direct, label-free manner and the ability to image in solution,
      providing real-time data acquisition under physiologically relevant conditions. A
      novel application of the AFM currently under development combines its surface
      profiling capabilities with fixed immuno-capture using antibodies immobilized in
      a nanoarray format. This provides a distinctive platform for direct, label-free
      detection and characterization of viral particles and other pathogens.

PMID- 15452336
TI  - SpeedScreen: The "missing link" between genomics and lead discovery.
AB  - SpeedScreen is a novel, label-free, in-solution, affinity-based selection
      methodology for high-throughput screening (HTS) developed at Novartis Pharma. The
      SpeedScreen protocol comprises in-solution affinity selection, followed by size
      exclusion chromatography in combination with microbore-liquid
      chromatography/electrospray-ionization mass spectrometry (micro-LC/ESI-MS). The
      authors describe the basic concept behind assay development, HTS, and data
      analysis with the SpeedScreen technology. Advantages and limitations of
      SpeedScreen compared to alternative screening technologies are discussed, and an
      example is given from a SpeedScreen campaign applying this innovative affinity
      selection concept in HTS.

PMID- 15452337
TI  - Comparison of the usefulness of the MTT, ATP, and calcein assays to predict the
      potency of cytotoxic agents in various human cancer cell lines.
AB  - Cell viability assays are important tools in oncological research and clinical
      practice to assess the tumor cell sensitivity of individual patients. The purpose
      of this study was to demonstrate the comparability of 3 widely used assays (MTT,
      ATP, calcein assays) by principal component analysis. The study included 4
      different cytostatics (cisplatin, docetaxel, doxorubicin, vinblastine) and 3
      different human cancer cell lines (MCF-7, A2780, doxorubicin resistant A2780adr).
      Ninety-three percent of the total variance of all variables included in the
      principal component analysis (resulting from 3 cell lines and 3 assays) could be
      explained by 1 principal component. Factor loadings were > 0.937 except for the
      variable MTT-A2780adr, which was 0.872. These results indicate the similarity of
      the 3 assays. A 2nd principal component analysis included literature data and
      showed accordance of data from this study and the literature. The MTT assay was
      further improved as a high-throughput screening-capable assay. The ATP assay is
      able to detect effects of cytostatics already after 1 h incubation. The
      determination of resistance factors allowed to differentiate cytostatics into P
      gp or non-P-gp substrates. In conclusion, this study provides improved microplate
      reader-based cell viability assays and sets a statistically solid basis for a
      future comparison of data obtained in different laboratories by any of the 3
      assays.

PMID- 15452338
TI  - Development and automation of a 384-well cell fusion assay to identify inhibitors
      of CCR5/CD4-mediated HIV virus entry.
AB  - This article describes the automation of an in vitro cell-based fusion assay for
      the identification of novel inhibitors of receptor mediated HIV-1 entry. The
      assay utilises two stable cell lines: one expressing CD4, CCR5 and an LTR
      promoter/beta-galactosidase reporter construct, and the other expressing gp160
      and tat. Accumulation of beta-galactosidase can only occur following fusion of
      these two cell lines via the gp160 and receptor mediators, as this event
      facilitates the transfer of the tat transcription factor between the two cell
      types. Although similar cell fusion systems have been described previously, they
      have not met the requirements for HTS due to complexity, throughput and reagent
      cost. The assay described in this article provides significant advantage, as (a)
      no transfection/infection events are required prior to the assay, reducing the
      potential for variability, (b) cells are mixed in solution, enhancing fusion
      efficiency compared to adherent cells, (c) miniaturization to low volume enables
      screening in 384-well plates; and (d) online cell dispensing facilitates
      automated screening. This assay has been employed to screen approximately 650,000
      compounds in a singleton format. The data demonstrate that the assay is robust,
      with a Z' consistently above 0.6, which compares favourably with less complex
      biochemical assays.

PMID- 15452339
TI  - Utilization of fluorescence polarization and time resolved fluorescence resonance
      energy transfer assay formats for SAR studies: Src kinase as a model system.
AB  - High-throughput screening (HTS), a major component of lead identification, often
      utilizes fluorescence-based assay technologies. For example, HTS kinase assays
      are formatted using a variety of fluorescence-based assay technologies including,
      but not limited to, dissociation enhanced lanthanide fluoroimmunoassay (DELFIA),
      time-resolved fluorescence resonance energy transfer (TR-FRET), and fluorescence
      polarization (FP). These assays offer tremendous advantages such as a
      nonradioactive format, ease of automation, and excellent reproducibility.
      Fluorescence-based assays frequently used for lead identification can also be
      useful for structure activity relationship (SAR) studies during lead
      optimization. An important issue when assessing an assay to be used for SAR is
      the ability of the assay to discriminate high-affinity small molecule inhibitors
      (pM-nM) from low-affinity inhibitors (microM-mM). The purpose of this study was
      to utilize HTS-friendly assay formats for SAR by developing TR-FRET, FP, and
      DELFIAassays measuring Src kinase activity and to define the theoretical lower
      limit of small molecule inhibitor detection achievable with these assay formats.
      The authors show that 2 homogeneous assay formats, TR-FRET and FP, allowed for
      the development of Src kinase assays with a lower limit of detection of K(i) =
      0.01 nM. This study indicates that assay technologies typically used for HTS can
      be used during lead optimization by providing quantitative measurements of
      compound activity critical to driving SAR studies.

PMID- 15452340
TI  - Correlation of high-throughput pregnane X receptor (PXR) transactivation and
      binding assays.
AB  - Pregnane X receptor (PXR) transactivation and binding assays have been developed
      into high-throughput assays, which are robust and reproducible (Z' > 0.5). For
      most compounds, there was a good correlation between the results of the
      transactivation and binding assays. EC(50) values of compounds in the
      transactivation assay correlated reasonably well with their IC(50) values in the
      binding assay. However, there were discrepancies with some compounds showing high
      binding affinity in the binding assay translated into low transactivation. The
      most likely cause for these discrepancies was an agonist-dependent relationship
      between binding affinity and transactivation response. In general, compounds that
      bound to human PXR and transactivated PXR tended to be large hydrophobic
      molecules.

PMID- 15452341
TI  - Molecular dynamics studies of ground state and intermediate of the
      hyperthermophilic indole-3-glycerol phosphate synthase.
AB  - Indole-3-glycerol phosphate synthase catalyzes the terminal ring closure step in
      tryptophan biosynthesis. In this paper, we compare the results from molecular
      dynamics (MD) simulations of enzyme-bound substrate at 298, 333, 363, and 385 K
      and the enzyme-bound intermediate at 385 K, solvated in TIP3P water box with a
      CHARMM force field. Results from MD simulations agree with experimental studies
      supporting the observation that Lys-110 is the general acid. Based on its
      location in the active site during the MD simulations, Glu-210 warrants
      classification as the general base instead of the previously proposed Glu-159. We
      find that the relative population of the reactive enzyme-substrate Michaelis
      conformers [near attack conformers (NACs)] with temperature correlates well
      (correlation coefficient of 0.96) with the relative activity of this thermophilic
      enzyme. At higher temperature, the enzyme-substrate electrostatic interaction
      favors the binding of the substrate in NAC conformation, whereas, at lower
      temperature, the substrate is distorted and bound in a nonreactive conformation.
      This change is reflected in the approximately 1,100-fold increase in population
      of NACs at 385 K relative to 298 K. The easily determined population of NACs at
      given temperature tells much about the thermophilic property of the enzyme. Thus,
      the hyperthermophilic enzyme has evolved to have optimum activity at high
      temperatures, and, with lowering of the temperature, the electrostatic
      interaction at the active site is enhanced and the structure is deformed. This
      model can be regarded as a general explanation for the activity of
      hyperthermophilic enzymes.

PMID- 15452342
TI  - Biochemical identification of Argonaute 2 as the sole protein required for RNA
      induced silencing complex activity.
AB  - RNA interference is carried out by the small double-stranded RNA-induced
      silencing complex (RISC). The RISC-bound small RNA guides the RISC complex to
      identify and cleave mRNAs with complementary sequences. The proteins that make up
      the RISC complex and cleave mRNA have not been unequivocally defined. Here, we
      report the biochemical purification of RISC activity to homogeneity from
      Drosophila Schnieder 2 cell extracts. Argonaute 2 (Ago-2) is the sole protein
      component present in the purified, functional RISC. By using a bioinformatics
      method that combines sequence-profile analysis with predicted protein secondary
      structure, we found homology between the PIWI domain of Ago-2 and endonuclease V
      and identified potential active-site amino acid residues within the PIWI domain
      of Ago-2.

PMID- 15452343
TI  - Systematic investigation of protein phase behavior with a microfluidic
      formulator.
AB  - We demonstrated a microfluidic device for rapidly generating complex mixtures of
      32 stock reagents in a 5-nl reactor. This "formulation chip" is fully automated
      and allows thousands of experiments to be performed in a single day with minimal
      reagent consumption. It was applied to systematically study the phase behavior of
      the protein xylanase over a large and complex chemical space. For each chemical
      formulation that demonstrated a pronounced effect on solubility, the protein
      phase behavior was completely mapped in the chip, generating a set of empirical
      phase diagrams. This ab initio phase information was used to devise a rational
      crystallization screen that resulted in 72-fold improvement in successful
      crystallization hits compared with conventional sparse matrix screens. This
      formulations tool allows a physics-based approach to protein crystallization that
      may prove useful in structural genomics efforts.

PMID- 15452344
TI  - A nuclear receptor corepressor transcriptional checkpoint controlling activator
      protein 1-dependent gene networks required for macrophage activation.
AB  - The nuclear receptor corepressor (NCoR) and the related factor known as silencing
      mediator of retinoic acid and thyroid hormone receptor (SMRT) are essential
      components of multiprotein complexes that mediate active repression by unliganded
      nuclear receptors. Recent studies suggest that NCoR and SMRT can interact with
      and exert repressive effects on several other classes of DNA-binding
      transcription factors, but the physiological importance of these interactions has
      not been established. Here, investigation of endogenous transcriptional programs
      regulated by NCoR in macrophages reveals that NCoR acts as a transcriptional
      checkpoint for activator protein (AP)-1-dependent gene networks that regulate
      diverse biological processes including inflammation, cell migration, and collagen
      catabolism, with loss of NCoR, resulting in derepression of AP-1 target genes.
      The NCoR corepressor complex imposes an active block of exchange of c-Jun for c
      Jun/c-Fos heterodimers, with targeted deletion of the c-Jun locus, resulting in
      loss of NCoR complexes from AP-1 target genes under basal conditions. The
      checkpoint function of NCoR is relieved by signal-dependent phosphorylation of c
      Jun, which directs removal of NCoR/HDAC3/TBL1/TBLR1 complexes through recruitment
      of a specific ubiquitylation complex, as a prerequisite to the default binding of
      c-Jun/c-Fos heterodimers and transcriptional activation. The requirement for a
      checkpoint function to achieve the appropriate dynamic range of transcriptional
      responses to inflammatory signals is likely to be used by other signal-dependent
      transcription factors that regulate diverse homeostatic and developmental
      processes.

PMID- 15452345
TI  - Correlation between tumor regression and T cell responses in melanoma patients
      vaccinated with a MAGE antigen.
AB  - The cancer-germline gene MAGE-3 codes for tumor-specific antigens recognized on
      many tumors by T lymphocytes. A MAGE-3 antigen presented by HLA-A1 has been used
      in several vaccination trials on metastatic melanoma patients. Only a small
      minority of patients have shown evidence of tumor regression. Attempts to
      correlate the tumor rejections with the cytotoxic T lymphocyte (CTL) response
      against the vaccine have been hampered by the low level of these responses. In
      noncancerous individuals, the frequency of the T cell precursors against antigen
      MAGE-3.A1 is approximately 4 x 10(-7) CD8 T cells. The diversity of the T cell
      receptor repertoire of these anti-MAGE-3.A1 precursors was analyzed in one
      individual. The results indicate that it is very likely that the repertoire
      comprises >100 clonotypes. On this basis, it is possible to use not only the
      frequency of CTL precursors in the blood but also the presence of dominant
      clonotypes to ascertain in patients the existence of anti-MAGE-3.A1 responses as
      low as 10(-6) of CD8. With this approach, we observed a correlation between tumor
      regression and anti-MAGE-3.A1 CTL responses in patients vaccinated with a
      recombinant virus encoding the antigen and also in patients vaccinated with
      peptide-pulsed dendritic cells. In contrast, for patients showing tumor
      regression after vaccination with peptide alone, CTL responses were almost never
      observed. It is possible that even those CTL responses that are below our present
      detection level can trigger a sequence of events that leads to tumor regression.

PMID- 15452346
TI  - Elementary inequalities that involve two nonnegative vectors or functions.
AB  - We report 96 inequalities with common structure, all elementary to state but many
      not elementary to prove. If n is a positive integer, a = (a1,..., an) and b =
      (b1,..., bn) are arbitrary vectors in R(+)n=[0,infinity)n, and rho(mij) is the
      spectral radius of an n x n matrix with elements m(ij), then, for example:
      [equation: see text]. The second inequality is obtained from the first inequality
      by replacing min with max and x with + and by reversing the direction of the
      inequality. The third inequality is obtained from the first by replacing the
      summation by the spectral radius. The fourth inequality is obtained from the
      first by taking each summand as a coefficient in a quadratic form. The fifth
      inequality is obtained from the first by replacing both outer summations by
      products, min by x, x by +, and the nonnegative vectors a and b by nonnegative
      measurable functions f and g. The proofs of these inequalities are mysteriously
      diverse.

PMID- 15452347
TI  - Regulatory potential and control of Foxp3 expression in newborn CD4+ T cells.
AB  - Thymectomy at day 3 after birth leads to autoimmune disease in some genetic
      backgrounds. Disease is thought to be caused by the lack/paucity of regulatory T
      cells. We show that 3-day-old mice already contain a significant compartment of
      Foxp3-expressing CD25(+)CD4(+) splenocytes. Whereas, in adult spleen, the subsets
      of regulatory T cells (CD25(+) and/or CD103(+)) express high amounts of Foxp3
      mRNA, in 3-day-old mice, both thymic and splenic CD25(+)CD4(+) T cell subsets
      express lower amounts of Foxp3 mRNA, and CD103(+) cells are barely detected. In
      adult day 3-thymectomized mice, the CD25(+)CD4(+) T cell subset is
      overrepresented (most of the cells being CD103(+)) and expresses high amounts of
      Foxp3 mRNA, independent of the development of autoimmune gastritis. These cells
      control inflammatory bowel disease and the homeostatic expansion of lymphocytes.
      This study demonstrates that the peripheral immune system of newborn mice is
      endowed of a remarkable regulatory potential, which develops considerably in the
      absence of thymic supply.

PMID- 15452348
TI  - Spatial memory, recognition memory, and the hippocampus.
AB  - There is wide agreement that spatial memory is dependent on the integrity of the
      hippocampus, but the importance of the hippocampus for nonspatial tasks,
      including tasks of object recognition memory is not as clear. We examined the
      relationship between hippocampal lesion size and both spatial memory and object
      recognition memory in rats. Spatial memory was impaired after bilateral dorsal
      hippocampal lesions that encompassed 30-50% total volume, and as lesion size
      increased from 50% to approximately 100% of total hippocampal volume, performance
      was similarly impaired. In contrast, object recognition was intact after dorsal
      hippocampal lesions that damaged 50-75% of total hippocampal volume and was
      impaired only after larger lesions that encompassed 75-100% of hippocampal
      volume. Last, ventral hippocampal lesions that encompassed approximately 50% of
      total hippocampal volume impaired spatial memory but did not affect object
      recognition memory. These findings show that the hippocampus is important for
      both spatial memory and recognition memory. However, spatial memory performance
      requires more hippocampal tissue than does recognition memory.

PMID- 15452349
TI  - Masking and scrambling in the auditory thalamus of awake rats by Gaussian and
      modulated noises.
AB  - This paper provides a look at how modulated broad-band noises modulate the
      thalamic response evoked by brief probe sounds in the awake animal. We
      demonstrate that noise not only attenuates the response to probe sounds (masking)
      but also changes the temporal response pattern (scrambling). Two brief probe
      sounds, a Gaussian noise burst and a brief sinusoidal tone, were presented in
      silence and in three ongoing noises. The three noises were targeted at activating
      the auditory system in qualitatively distinct ways. Dynamic ripple noise,
      containing many random tone-like elements, is targeted at those parts of the
      auditory system that respond well to tones. International Collegium of
      Rehabilitative Audiology noise, comprised of the sum of several simultaneous
      streams of Schroeder-phase speech, is targeted at those parts of the auditory
      system that respond well to modulated sounds but lack a well defined response to
      tones. Gaussian noise is targeted at those parts of the auditory system that
      respond to acoustic energy regardless of modulation. All noises both attenuated
      and decreased the precise temporal repeatability of the onset response to probe
      sounds. In addition, the modulated noises induced context-specific changes in the
      temporal pattern of the response to probe sounds. Scrambling of the temporal
      response pattern may be a direct neural correlate of the unfortunate experience
      of being able to hear, but not understand, speech sounds in noisy environments.

PMID- 15452350
TI  - Distinct ontogenic and regional expressions of newly identified Cajal-Retzius
      cell-specific genes during neocorticogenesis.
AB  - Cajal-Retzius (CR) cells are early-generated transient neurons and are important
      in the regulation of cortical neuronal migration and cortical laminar formation.
      Molecular entities characterizing the CR cell identity, however, remain largely
      elusive. We purified mouse cortical CR cells expressing GFP to homogeneity by
      fluorescence-activated cell sorting and examined a genome-wide expression profile
      of cortical CR cells at embryonic and postnatal periods. We identified 49 genes
      that exceeded hybridization signals by >10-fold in CR cells compared with non-CR
      cells at embryonic day 13.5, postnatal day 2, or both. Among these CR cell
      specific genes, 25 genes, including the CR cell marker genes such as the reelin
      and calretinin genes, are selectively and highly expressed in both embryonic and
      postnatal CR cells. These genes, which encode generic properties of CR cell
      specificity, are eminently characterized as modulatory composites of voltage
      dependent calcium channels and sets of functionally related cellular components
      involved in cell migration, adhesion, and neurite extension. Five genes are
      highly expressed in CR cells at the early embryonic period and are rapidly down
      regulated thereafter. Furthermore, some of these genes have been shown to mark
      two distinctly different focal regions corresponding to the CR cell origins. At
      the late prenatal and postnatal periods, 19 genes are selectively up-regulated in
      CR cells. These genes include functional molecules implicated in synaptic
      transmission and modulation. CR cells thus strikingly change their cellular
      phenotypes during cortical development and play a pivotal role in both
      corticogenesis and cortical circuit maturation.

PMID- 15452351
TI  - Restoration of an absent G1 arrest and protection from apoptosis in embryonic
      stem cells after ionizing radiation.
AB  - Response to DNA damage and cell-cycle regulation differ markedly between
      embryonic stem (ES) cells and somatic cells. ES cells require exquisitely
      sensitive mechanisms to maintain genomic integrity and do so, in part, by
      suppressing spontaneous mutation. Spontaneous mutation frequency in somatic cells
      is approximately 10(-4) compared with 10(-6) for ES cells. ES cells also lack a
      G(1) checkpoint and are hypersensitive to IR and other DNA-damaging agents. These
      characteristics facilitate apoptosis and the removal of cells with a mutational
      burden from the population, thereby keeping the population free of damaged cells.
      Here, we identify signaling pathways that are compromised and lead to a natural
      absence of aG(1) arrest in ES cells after DNA damage. The affected pathways are
      those mediated by p53 and p21 and by ATM, Chk2, Cdc25A, and Cdk2. In ES cells,
      Chk2 kinase is not intranuclear as in somatic cells but is sequestered at
      centrosomes and is unavailable to phosphorylate Cdc25A phosphatase and cause its
      degradation. Although ectopic expression of Chk2 does not rescue the p53/p21
      pathway, its expression is sufficient to allow it to phosphorylate Cdc25A,
      activate downstream targets, restore a G(1) arrest, and protect the cell from
      apoptosis.

PMID- 15452352
TI  - Identification of a major locus for age-related cortical cataract on chromosome
      6p12-q12 in the Beaver Dam Eye Study.
AB  - Age-related cataracts are one of the leading causes of visual impairment and
      blindness among the elderly worldwide. Among age-related cataracts, cortical
      opacities rank as the second most common type; however, little is known about
      their molecular pathogenesis or genetics. To identify susceptibility loci for
      cortical cataracts, we genotyped a subset of families (102 families; n = 224 sib
      pairs) from the Beaver Dam Eye Study and performed a model-free genome-wide
      linkage analysis for markers linked to a quantitative measure of cortical
      opacity. We obtained evidence for linkage at marker D1S1622 on chromosome 1p35 (P
      < 0.0002) and at marker D6S1053 on 6q12 (P < 0.00008) in the initial scan. Five
      additional regions on 1q31, 2p24, 2q11, 4q28, and 15q13 that are suggestive of
      linkage (P < or = 0.01 or logarithm of the likelihood ratio > or = 1.18) were
      observed. The region on chromosomes 6p12-q12 was selected for fine mapping, and
      the intermarker distance was reduced to 3 cM by adding 11 markers in the interval
      between D6S1017 and D6S1021. After fine mapping, significant evidence of linkage
      remained on chromosome 6p12-q12 at D6S1053 (P < 0.00005). The current genome scan
      for age-related cortical cataracts may lead to identification of novel genes,
      because few regions identified in the current scan have previously been
      implicated in congenital or age-related cataracts.

PMID- 15452353
TI  - Exercises in prognostication: crystal structures and protein folding.

PMID- 15452354
TI  - Foxa2 is required for transition to air breathing at birth.
AB  - Toward the end of gestation in mammals, the fetal lung undergoes a process of
      differentiation that is required for transition to air breathing at birth.
      Respiratory epithelial cells synthesize the surfactant proteins and lipids that
      together form the pulmonary surfactant complex necessary for lung function.
      Failure of this process causes respiratory distress syndrome, a leading cause of
      perinatal death and morbidity in newborn infants. Here we demonstrate that
      expression of the forkhead gene Foxa2 in respiratory epithelial cells of the
      peripheral lung controls pulmonary maturation at birth. Newborn mice lacking
      Foxa2 expression in the lung develop severe pulmonary disease on the first day of
      life, with all of the morphological, molecular, and biochemical features of
      respiratory distress syndrome in preterm infants, including atelectasis, hyaline
      membranes, and the lack of pulmonary surfactant lipids and proteins. RNA
      microarray analysis at embryonic day 18.5 demonstrated that Foxa2-regulated
      expression of a group of genes mediating surfactant protein and lipid synthesis,
      host defense, and antioxidant production. Foxa2 regulates a complex pulmonary
      program of epithelial cell maturation required for transition to air breathing at
      birth.

PMID- 15452355
TI  - Long-range intramolecular signaling in a tRNA synthetase complex revealed by pre
      steady-state kinetics.
AB  - Pre-steady-state kinetic studies of Escherichia coli glutaminyl-tRNA synthetase
      conclusively demonstrate the existence of long-distance pathways of communication
      through the protein-RNA complex. Measurements of aminoacyl-tRNA synthesis reveal
      a rapid burst of product formation followed by a slower linear increase
      corresponding to k(cat). Thus, a step after chemistry but before regeneration of
      active enzyme is rate-limiting for synthesis of Gln-tRNA(Gln). Single-turnover
      kinetics validates these observations, confirming that the rate of the chemical
      step for tRNA aminoacylation (k(chem)) exceeds the steady-state rate by nearly 10
      fold. The concentration dependence of the single-turnover reaction further
      reveals that the glutamine K(d) is significantly higher than the steady-state
      K(m) value. The separation of binding from catalytic events by transient kinetics
      now allows precise interpretation of how alterations in tRNA structure affect the
      aminoacylation reaction. Mutation of U35 in the tRNA anticodon loop decreases
      k(chem) by 30-fold and weakens glutamine binding affinity by 20-fold,
      demonstrating that the active-site configuration depends on enzyme-tRNA contacts
      some 40 A distant. By contrast, mutation of the adjacent G36 has very small
      effects on k(chem) and K(d) for glutamine. Together with x-ray crystallographic
      data, these findings allow a comparative evaluation of alternative long-range
      signaling pathways and lay the groundwork for systematic exploration of how
      induced-fit conformational transitions may control substrate selection in this
      model enzyme-RNA complex.

PMID- 15452356
TI  - Measuring single-molecule nucleic acid dynamics in solution by two-color filtered
      ratiometric fluorescence correlation spectroscopy.
AB  - This work presents a general method for determining single-molecule
      intramolecular dynamics in biomolecules by using a reporter fluorophore, whose
      fluorescence is quenched or partially quenched as a result of intramolecular
      motion, and a remote observer fluorophore. These fluorophores were excited
      independently with two different lasers, and the ratio of the two fluorophores'
      fluorescence was calculated. The time-varying ratio was then filtered to reduce
      contributions from molecules outside the overlapped laser volume and then
      correlated. The rates of opening and closing of a DNA hairpin were measured by
      using both fluorescence correlation spectroscopy and this method for comparison.
      We found at 50 pM, where molecules were studied one by one as they diffused
      through the probe volume, we obtained accurate opening and closing rates and
      could also measure dynamic heterogeneity. To demonstrate applicability to a more
      complex biological molecule we then probed intramolecular motions in the dimer of
      a human telomerase RNA fragment (hTR(380-444)), in the presence of an excess of
      monomer. The motion was found to occur on the time scale of 180-750 micros and
      slowed with increasing magnesium ion concentration. Blocking experiments using
      complementary oligonucleotides suggested that the motion involves substantial
      changes in dimer tertiary structure. This method appears to be a general method
      for selectively studying intramolecular motion in large biomolecules or
      complexes.

PMID- 15452357
TI  - Treatment of surfactant-damaged skin in humans with creams of different pH
      values.
AB  - Skin surface has an acidic pH, whereas the body's internal environment maintains
      a near-neutral pH. The physiological role of the 'acidic mantle' and the function
      of the pH gradient throughout the stratum corneum remain unexplained. The pH
      gradient has been suggested to activate enzymes responsible for the maintenance
      of the skin barrier function and to facilitate the desquamation process in the
      stratum corneum. The aim of the study was to investigate the influence of pH of a
      moisturizing cream on barrier recovery in surfactant-damaged human skin.
      Volunteers had their skin damaged with sodium lauryl sulphate and treated those
      areas with the cream, adjusted to either pH 4.0 or 7.5. The study did not prove
      the superiority of a cream of pH 4.0 to a cream of pH 7.5 regarding promotion of
      skin barrier recovery, since no significant differences (p > 0.05) were found in
      transepidermal water loss, blood flow and skin capacitance between the treated
      areas.

PMID- 15452358
TI  - Brain but not spinal NR2B receptor is responsible for the anti-allodynic effect
      of an NR2B subunit-selective antagonist CP-101,606 in a rat chronic constriction
      injury model.
AB  - In order to examine the site of action of an NR2B subtype-selective NMDA
      antagonist CP-101,606, we investigated its analgesic effect in a rat model of
      neuropathic pain at various routes of administration. Mechanical allodynia was
      induced by chronic constriction injury (CCI) of the sciatic nerve in male Sprague
      Dawley rats. Subcutaneous treatment of the animals with CP-101,606 at 10 mg/kg
      significantly inhibited CCI-induced mechanical allodynia. Intracerebroventricular
      injection of CP-101,606 at 10, 30 and 100 nmol also inhibited the mechanical
      allodynia in a dose-dependent manner, the statistically significant effect being
      achieved at the highest dose tested (100 nmol) without producing any behavioral
      abnormalities. However, intrathecal injection of CP-101,606 at a dose of 300 nmol
      failed to inhibit CCI-induced allodynia. A receptor binding assay using rat
      forebrain and spinal cord membrane preparations demonstrated that [3H]CP-101,606
      bound to the brain NR2B receptor with a greater extent compared to the spinal
      cord one. These findings suggest that the anti-allodynia effect of CP-101,606 is
      ascribable to blockade of NR2B receptors at the brain, but not at the spinal
      cord. In contrast, intrathecal injection of a non-selective NMDA antagonist,
      memantine, significantly inhibited CCI-induced mechanical allodynia at a dose of
      300 nmol, indicating the difference in the site of action between the non
      selective NMDA antagonist and the NR2B-specific NMDA antagonist.

PMID- 15452359
TI  - Novel PPARgamma agonists GI 262570, GW 7845, GW 1929, and pioglitazone decrease
      calcium channel function and myogenic tone in rat mesenteric arteries.
AB  - Novel non-thiazolidinedione, tyrosine-derived peroxisome proliferator-activated
      receptor gamma agonists, GI 262570, GW 7845, GW 1929, developed by
      GlaxoSmithKline (GSK) along with pioglitazone and nisoldipine, were studied on
      currents through L-type voltage-dependent calcium channels (VDCC) in freshly
      isolated smooth muscle cells from mesenteric arteries, and on the diameter of
      pressurized mesenteric arteries in vitro. Using Ba2+ (10 mmol/l) as the charge
      carrier through VDCC, the half-inhibition constants (IC50) for GI 262570, GW
      7845, GW 1929, and pioglitazone were 2.0 +/- 0.5, 3.0 +/- 0.5, 5.0 +/- 0.7, and
      10.0 +/- 0.8 mumol/l, respectively. For arterial diameter measurements the IC50
      values for GI 262570, GW 7845, GW 1929, and pioglitazone were 2.4, 4.1, 6.3, and
      13.9 mumol/l, respectively. Each GSK compound and pioglitazone was effective at
      inhibiting VDCC and relaxing pressurized arteries, suggesting that the
      vasodilation of resistance arteries could be explained by the inhibition of
      calcium entry through VDCC.

PMID- 15452360
TI  - Modulation of urokinase-type plasminogen activator by transforming growth factor
      beta1 in acetaldehyde-activated hepatic stellate cells.
AB  - The aim of this study was to determine whether transforming growth factor-beta1
      (TGF-beta1) induces the synthesis, release and gene expression of urokinase-type
      plasminogen activator (uPA) in hepatic stellate cells. In addition to stimulating
      collagen production, TGF-beta1 induced the morphological and phenotypical changes
      characteristic of hepatic stellate cell activation. However, these changes
      accentuated in cells previously activated with acetaldehyde. TGF-beta1 increased
      to 2-fold uPA activity in lysates from quiescent cells, and to 3.5-fold in
      activated cells, and induced uPA gene expression to the same extent in both
      activated and non-activated cells. TGF-beta1 had a modest stimulatory action on
      the release of uPA into the conditioned medium, but reduced acetaldehyde-induced
      release, as demonstrated by Western blot analysis. In accord, whereas TGF-beta1
      produces no effect on uPA activity in the conditioned media from quiescent cells,
      it significantly reduces the stimulatory action of acetaldehyde. These results
      show that the activity and gene expression of uPA are regulated by both
      acetaldehyde and TGF-beta1 and that the proteolytic activity in the extracellular
      space is reduced by the influence of TGF-beta1. Further studies on the molecular
      mechanisms responsible for the regulation of the plasminogen system by TGF-beta1
      and other molecules in the presence of acetaldehyde will contribute to a better
      understanding of the processes involved in fibrogenesis.

PMID- 15452361
TI  - Montelukast, a cysteinyl leukotriene receptor-1 antagonist, dose- and time
      dependently protects against focal cerebral ischemia in mice.
AB  - Our previous studies showed that cysteinyl leukotriene receptor-1 (CysLT1)
      antagonist pranlukast has a neuroprotective effect on cerebral ischemia in rats
      and mice. However, whether the neuroprotective effect of pranlukast is its
      special action or a common action of CysLT1 receptor antagonists remains to be
      clarified. This study was performed to determine whether montelukast, another
      CysLT1 receptor antagonist, has the neuroprotective effect on focal cerebral
      ischemia in mice, and to observe its dose- and time-dependent properties.
      Permanent focal cerebral ischemia was induced by middle cerebral artery occlusion
      (MCAO). Montelukast was injected intraperitoneally either as multiple doses (once
      a day for 3 days and 30 min before MCAO) or as a single dose (at 30 min before,
      30 min after, or 1 h after MCAO), respectively, and pranlukast and edaravone were
      used as controls. The neurological deficits, infarct volumes, brain edema, neuron
      density, and Evans blue extravasation in the brain were determined 24 h after
      MCAO. Pretreatments with multiple doses or a single dose of montelukast (0.1 and
      1.0 mg/kg) before MCAO significantly attenuated all the ischemic insults. Post
      treatment with a single dose of montelukast (0.1 and 1.0 mg/kg) at 30 min after
      MCAO also significantly decreased brain edema and infarct volume, but not
      neurological deficits. However, post-treatment with a single dose of montelukast
      at 1 h after MCAO had no significant effect. Pranlukast showed the same effects
      as montelukast, but edaravone attenuated the ischemic insults only with multiple
      doses before MCAO. Thus, montelukast has a dose- and time-dependent
      neuroprotective effect on permanent focal cerebral ischemia in mice, with an
      effective dose range of 0.1-1.0 mg/kg and a therapeutic window of 30 min. These
      findings further support the therapeutic potential of CysLT1 receptor antagonists
      in the treatment of cerebral ischemia at earlier phases.

PMID- 15452362
TI  - Therapeutic potential of new Pt(II) and Ru(III) triazole-pyrimidine complexes
      against Leishmania donovani.
AB  - We have already established an in vitro culture system using murine macrophages
      infected with Leishmania donovani in which the time course of parasite growth is
      determined quantitatively. We adopted this system for the screening of three
      triazole-pyrimidine derivatives that would ideally prove to be effective against
      L. donovani with no toxicity to the host cell. Amphotericin B deoxycholate was
      used as the standard drug and gave a IC50 value of 3.89 microg/ml. The three
      triazole-pyrimidine compounds assayed have been reported to be potent growth
      inhibitors of L. donovani promastigote and amastigote stages. Compounds SPIV and
      SPVI exhibited the highest toxicity for extracellular forms of parasites, with
      IC50 values of 19.95 and 21.61 microg/ml, respectively. The triazole-pyrimidine
      SPV, although to a lower degree, also showed pronounced effects against
      promastigote forms with IC50 of 33.14 microg/ml. Drug activity was higher against
      amastigote than against promastigote stages. The compounds SPIV and SPVI
      interfered with the synthesis of macromolecules, affecting primarily DNA at the
      lower concentration tested (5 microg/ml), while SPV also showed interference,
      though to a lesser extent, and at a higher concentration (15 microg/ml) the
      percentage of inhibition rose considerably. The synthesis or RNA and proteins was
      also depressed significantly by these compounds at administration rates of 15
      microg/ml. Ultrastructural alterations were evident in the main organelles of L.
      donovani (nucleus, kinetoplast, mitochondria), after the addition of the three
      compounds at a concentration of 5 microg/ml, to the in vitro culture. The in
      vitro promastigote forms of L. donovani can degrade glucose to carbon dioxide,
      and part of the carbon skeleton of the glucose is excreted as end metabolites.
      The excretion of these metabolites, mainly acetate, was also inhibited by the
      three compounds assayed, suggesting that this could be due to a direct effect on
      some of the enzymes related to this fermentation pathway or to the inhibition
      exerted by the compounds on enzyme synthesis.

PMID- 15452363
TI  - Reversal of experimental myoglobinuric acute renal failure in rats by quercetin,
      a bioflavonoid.
AB  - The occurrence of acute renal failure (ARF) following rhabdomyolysis has been put
      at between 10 and 40% of cases, and accounts for between 3 and 15% of all cases
      of ARF. Reactive oxygen intermediates have been demonstrated to play an
      etiological role in myoglobinuric renal failure. This study was performed to
      explore the protective effect of quercetin, a bioflavonoid, in an experimental
      model of myoglobinuric ARF in rats. Four groups of rats were employed in this
      study: group 1 served as control, group 2 was given 50% glycerol (8 ml/kg, i.m.),
      group 3 was given glycerol + quercetin (2 mg/kg, i.p.), and group 4 was given
      glycerol + DMSO (the solvent for quercetin, 5 ml/kg, i.p.). Renal injury was
      assessed by measuring serum creatinine, blood urea nitrogen, creatinine and urea
      clearance. The oxidative stress was measured by renal malondialdehyde levels,
      reduced glutathione levels and by enzymatic activity of catalase, glutathione
      reductase, and superoxide dismutase. Glycerol administration resulted in a marked
      renal oxidative stress, significantly deranged the renal functions as well as
      renal cytoarchitecture. All these factors were significantly improved by
      quercetin treatment. Because of its radical-scavenging and iron-chelating
      properties, quercetin protected the kidney against the glycerol-induced oxidative
      stress and resultant renal dysfunction. Based on these results, this study
      confirms the role of oxidative stress and demonstrates the renoprotective
      potential of quercetin in this rhabdomyolysis-mimicking model.

PMID- 15452364
TI  - Role of potassium channels in the frequency-dependent activity of regenerating
      nerves.
AB  - After a peripheral nerve injury, ion channel organization and the electrical
      properties of nerve fibers drastically change during the regeneration process.
      The present study was designed to compare the frequency-dependent characteristics
      of regenerating nerves in the presence of 4-aminopyridine (4-AP) and
      tetraethylammonium (TEA). The results showed that increasing the stimulus
      frequency produced a greater impulse blockade (frequency-dependent block--FDB)
      and distinct hyperpolarizing afterpotentials (HAPs) in regenerating nerves. In
      particular, regenerating sciatic nerves 15 days post-crush (dpc) were more
      sensitive to the frequency-dependent stimulations than 38-dpc and intact nerves
      in the presence or absence of drugs. The frequency-dependent effects of TEA on
      the compound action potentials (CAPs) appeared when TEA was applied to 4-AP
      treated nerves. This shows that TEA-sensitive channels may not be masked by the
      myelin. 4-AP was here found to have more pronounced frequency-dependent effects
      on regenerating nerves than on intact nerves. Delayed depolarization (in 38-dpc:
      22.6 +/- 1.3 mV and 47.52 +/- 3.63 ms, in intact: 12.0 +/- 1.9 mV and 88.51 +/-
      4.72 ms) elicited by 4-AP resulted in an increase in FDBs and HAP amplitudes.
      These results suggest that 4-AP-sensitive channels may play important roles in
      frequency-dependent nerve conduction. Consequently, regenerating or myelin
      damaged nerves are more sensitive to repetitive firing with or without drug. An
      understanding of the frequency-dependent properties of regenerating nerves may be
      of value in the treatment of the nerve diseases.

PMID- 15452365
TI  - Effects of modulation of the NO/cGMP pathway in tumor cell lines derived from the
      upper airway tract.
AB  - Nitric oxide (NO) is known to be expressed in a variety of cell types and exert
      its effects through autocrine and paracrine mechanisms. To characterize the
      NO/cGMP pathway in tumor cells of the upper airway tract, we studied the cell
      lines Detroit 562, FaDu and FAT7. Using isoform-specific antibodies, we were
      unable to detect expression of NO synthases in the above-mentioned cells lines.
      To evaluate whether tumor cells respond to NO, we exposed cells to the NO donor
      sodium nitroprusside (SNP). Stimulation of Detroit 562 and FaDu with SNP (10
      micromol/l to 1 mmol/l) led to a concentration-dependent increase in cGMP
      accumulation. In addition, incubation of cells with SNP, but not 8 Br-cGMP,
      reduced Detroit 562 cell number. As exposure of cells to SNP decreased (3)H
      thymidine incorporation without inducing DNA fragmentation, we attributed the
      observed decrease in cell number to inhibition of cell proliferation rather than
      induction of apoptosis. On the other hand, exposure of Detroit 562 to high
      concentrations of SNP (1 mmol/l) led to apoptosis and increased the release of
      vascular endothelial growth factor. We conclude that, although human cell lines
      derived from the upper airway tract do not produce NO, they respond to NO
      released by neighboring cells and that exposure to NO exerts an anti
      proliferative/apoptotic effect that is independent of cGMP generation.

PMID- 15452366
TI  - Comparison of the inhibitory efficacy of four belladonna drugs on
      gastrointestinal movement and cognitive function in food-deprived mice.
AB  - Belladonna drugs, scopolamine (Sco), atropine (Atr), anisodine (AT(3)), and
      anisodamine (Ani), frequently used for gastrointestinal motility disorders often
      produce adverse effects on the central nervous system. In the present work, these
      drugs (0.05, 0.5, 5, and 50 micromol kg(-1), i.p.) were evaluated for their
      potential to inhibit gastrointestinal motility and cognition in mice. Results
      showed that the maximum inhibitory rates of Sco, Atr, AT(3), and Ani on gastric
      emptying and small intestinal movement were 29.78, 40.69, 12.30, and 17.99% and
      51.98, 58.46, 46.51, and 46.22%, respectively. The affinities of Sco, Atr, AT(3),
      and Ani for muscarinic receptors in the whole mice were 1.62, 1.48, 2.28, and
      1.11 micromol kg(-1) for the stomach or 0.30, 1.12, 0.59, and 1.14 micromol kg(
      1) for the small intestine, respectively. The minimal effective doses for
      impairing avoidance-response learning were 5 micromol kg(-1) for Sco, Atr, or
      AT(3) and 50 micromol kg(-1) for Ani. The initial doses for insulting the
      avoidance-response memory or open-field memory were 0.5, 5, 5, and 50 micromol
      kg(-1) or 5, 5, 5, and >50 micromol kg(-1) for Sco, Atr, AT(3), and Ani,
      respectively. We conclude that the relative susceptibility of the mouse's tissue
      or function capacities towards the inhibitory effects of belladonna drugs is
      small intestine > stomach > avoidance-response memory > avoidance-response
      learning > open-field memory.

PMID- 15452367
TI  - Treatment with buserelin, an agonist of gonadotropin-releasing hormone,
      suppresses ovarian hyperstimulation syndrome induced in rabbits.
AB  - Human menopausal gonadotropin (hMG, 75 IU/body/day) and a gonadotropin-releasing
      hormone (GnRH) agonist buserelin (1, 10, 100 microg/kg/day) were simultaneously
      administered to female rabbits by the subcutaneous route for 7 days, and the
      effects on organ weights, plasma hormones and weight of ascitic fluid were
      examined. Treatment with hMG increased the ovarian weight, plasma estradiol and
      weight of ascites, thus indicating that ovarian hyperstimulation syndrome had
      been induced. Simultaneous treatment with buserelin decreased the changes induced
      by hMG. GnRH agonists can thus be surmised to reduce the severity of ovarian
      hyperstimulation syndrome in the rabbit. However, caution is needed when
      extrapolating the results of this rabbit model to humans.

PMID- 15452368
TI  - Modulatory effect of the PDE-5 inhibitor sildenafil in diabetic neuropathy.
AB  - Diabetic neuropathy is one of the most frequent peripheral neuropathies
      associated with hyperalgesia and hyperesthesia. Besides alteration in the levels
      of neurotransmitter, alteration in the neuronal nitric oxide synthase (nNOS) is a
      key factor in the pathogenesis of diabetic neuropathy. The present study was
      aimed at evaluating the role of PDE-5 inhibitor on nociception in streptozotocin
      induced diabetes in animal models of nociception (writhing assay in mice and paw
      hyperalgesia test in rats). Diabetic animals showed a significant decrease in
      pain threshold as compared to non-diabetic animals in both tests, indicating
      diabetes induced hyperalgesia in mice and rats. The PDE-5 inhibitor, sildenafil,
      significantly increased the pain threshold in both diabetic and non-diabetic
      animals. However, L-NAME, a non-specific NOS inhibitor and methylene blue (MB), a
      guanylate cyclase inhibitor blocked the antinociceptive effect. The per se
      administration of L-NAME or MB augmented the hyperalgesic response in diabetic
      animals with little or no effect in non-diabetic animals, indicating the
      alteration of NO-cGMP pathway in diabetes. The results in the present study
      demonstrate that the decreased nNOS-cGMP system may play a crucial role in the
      pathogenesis of diabetic neuropathy.

PMID- 15452369
TI  - Possible role of dexamethasone in sensitizing the beta-2-adrenergic receptor
      system in vivo in calves during concomitant treatment with clenbuterol.
AB  - Beta(2)-Agonists blunt the function of the beta-adrenoceptor G-protein adenylate
      cyclase-signalling system, whereas glucocorticoids reverse the agonist-mediated
      diminished beta-adrenergic responses; however, these effects have not been
      reported in vivo in calf lymphocytes. In this study, we first investigated the
      presence of the beta(2)-adrenergic receptors on calf lymphocytes, and second we
      tested the effects of either clenbuterol alone or in combination with
      dexamethasone on receptor expression and function (isoproterenol-induced
      intracellular adenosine 3',5'-cyclic monophosphate (cAMP) formation) in vivo. (-)
      [(125)I]-Iodocyanopindolol (ICYP) binding to intact calf lymphocytes was rapid,
      saturable (maximal number of binding sites 987 +/- 89 ICYP-binding sites/cell, n
      = 4) and of high affinity (K(D) value 17.23 +/- 2.8 pmol/l, n = 4). These binding
      sites were of the beta(2)-subtypes of adrenoceptors as indicated by the fact that
      beta-agonists inhibited ICYP binding with an order of potency: (-)-isoproterenol
      > (-)-adrenaline > (-)-noradrenaline. Furthermore, the selective beta(2)
      adrenoceptor antagonist ICI 118.551 was about >1,500 times more potent in
      inhibiting ICYP binding than was the beta(1)-selective adrenoceptor antagonist
      CGP 20712A. Consequently, calves were treated with clenbuterol (1.0 microg/kg
      b.i.d., i.v.) for 9 days alone or simultaneously with dexamethasone (0.1 mg/kg,
      i.v., once a day for 4 days). Clenbuterol decreased the number of lymphocyte
      beta(2)-adrenergic receptors by about 40-50% after only 48 h of drug
      administration. This was accompanied by a decrement in isoproterenol-induced
      lymphocyte cAMP formation. Upon application of both drugs, dexamethasone restored
      the clenbuterol-mediated decrease in beta(2)-adrenoceptors and cAMP production.
      Dexamethasone elevated the number of beta(2)-adrenoceptors and cAMP almost 1.5-
      to 2-fold at 24 h of drug administration, an effect that persisted for up to 24 h
      following drug withdrawal. Neither clenbuterol nor the combination with
      dexamethasone had an influence on the affinity of the receptor for the ligand.
      The present results demonstrate that dexamethasone in vivo upregulates the number
      and function of calf lymphocyte beta(2)-adrenoceptors, and thus enhances the
      sensitivity of the beta(2)-adrenoceptor signal-transduction pathway for
      clenbuterol during concomitant treatment with both drugs.

PMID- 15452370
TI  - Analysis of the effects of halothane on Gi-coupled muscarinic M2 receptor
      signaling in Xenopus oocytes using a chimeric G alpha protein.
AB  - Metabotropic G protein-coupled receptors have recently been recognized as targets
      for anesthetics and analgesics. In particular, G(q)-coupled receptors such as
      muscarinic M(1) receptors (M(1)R) and 5-hydroxytryptamine (5-HT) type 2A
      receptors have been reported to be targets for anesthetics. Much less is known,
      however, about the effects of anesthetics on G(i)-coupled receptors. Here we
      report a method to analyze functions of G(i)-coupled receptors in Xenopus oocytes
      expressing a chimeric G alpha protein. A chimeric G alpha(q) protein G
      alpha(qi5), which contains carboxy-terminus five amino acids of G alpha(i),
      enables G(i)-coupled receptors to couple to Gq-coupled receptor-mediated
      downstream pathways such as activation of phospholipase C. We determined
      acetylcholine (ACh)-induced Ca(2+)-activated Cl(-) currents in Xenopus oocytes
      coexpressing G(i)-coupled muscarinic M(2)receptors (M(2)R) with the chimeric G
      alpha(qi5). Although ACh did not induce any currents in oocytes expressing M(2)R
      alone, it caused robust Cl(-) currents in oocytes coexpressing M(2)R with G
      alpha(qi5). The EC(50) of the ACh-induced Cl(-) current mediated through G
      alpha(qi5) was 0.2 micromol/l, which was 2.2 times higher than that of the ACh
      induced G protein-activated inwardly rectifying K(+) currents activated by G beta
      gamma subunits liberated from endogenously expressed G alpha(i) in Xenopus
      oocytes. Other G(i)-coupled somatostatin type 2, 5-HT(1A) and delta-opioid
      receptors, when coexpressed with G alpha(qi5) in oocytes, also caused robust
      Ca(2+)-activated Cl(-) currents. In oocytes coexpressing M(2)R and G alpha(qi5),
      a volatile anesthetic halothane inhibited M(2)R-induced Cl(-) currents in a
      concentration-dependent manner with the IC(50) of 1.1 mmol/l, suggesting that
      halothane inhibits M(2)R-induced cellular responses at clinically relevant
      concentrations. Treatment with the protein kinase C inhibitor GF109203X produced
      a 3.5-fold enhancement of the initial Cl(-) currents induced by 1 micromol/l ACh
      in oocytes expressing M(2)R and G(qi5). The rate of halothane-induced inhibition
      of Cl(-) currents elicited by ACh, however, was not changed in such oocytes
      pretreated with GF109203X. These findings suggest that halothane inhibits the
      M(2)R-induced signaling by acting at sites other than PKC activity. Collectively
      these findings suggest that the use of oocyte expressing G alpha(qi5) would be
      helpful to examine the effects of anesthetics or analgesics on the function of
      G(i)-coupled receptors in the Xenopus oocyte expression system.

PMID- 15452371
TI  - Expression of S100A4 and Met: potential predictors for metastasis and survival in
      early-stage breast cancer.
AB  - BACKGROUND: To formulate individually tailored therapy for patients with early
      stage breast cancer, it is necessary to identify biomarkers for predicting
      metastasis and survival. METHODS: A homogeneous cohort of 92 T1-2N0M0 breast
      carcinoma patients with a long-term follow-up were divided into two groups: the
      metastasis group (n = 41) and the disease-free group (n = 51). We evaluated the
      ability of risk discrimination of six biomarkers, including S100A4, Met, bcl-2,
      p53, survivin, and HER-2/neu, in early-stage breast cancer. RESULTS: In multiple
      logistic regression analysis, only S100A4 expression (odds ratio = 5.37, p =
      0.008) and Met expression (odds ratio = 6.91, p = 0.002) were independent
      predictors of distant relapse. Multivariate Cox models showed S100A4 and Met
      expressions were associated with 10-year disease-free survival (DFS) (risk ratio
      3.2 and 4.0, respectively); however, tumor size and histological grade were not
      significant predictors. The 10-year DFS of T1-2N0M0 patients was 55.4%. T1-2N0M0
      patients with S100A4-positive tumors had a significantly worse 10-year DFS than
      those with S100A4-negative tumors (29.0 vs. 68.9 %, p = 0.001). The 10-year DFS
      in T1-2N0M0 patients with Met-negative tumors was 82.4 vs. 39.7% if Met
      expression was positive (p = 0.0002). S100A4, but not Met, was still a
      significant predictor of 10-year DFS in T1N0M0 breast carcinoma patients (p =
      0.02). For the T2N0M0 subgroup, both S100A4 and Met were significantly correlated
      with survival. The 10-year DFS of T2N0M0 patients with S100A4-negative and Met
      negative tumors was 92.3%; in those with S100A4-positive and Met-positive tumors,
      however, it was only 11.8%. CONCLUSIONS: S100A4 expression is an indicator of a
      poor prognosis for T1N0M0 breast cancer. In addition, the combination of S100A4
      and Met expression gives the best risk group discrimination in the T2N0M0
      subgroup. S100A4 expression appears to be an earlier step in the metastatic
      progression compared to Met expression in early-stage breast carcinoma.

PMID- 15452372
TI  - Development of a cancer pain assessment tool in Korea: a validation study of a
      Korean version of the brief pain inventory.
AB  - OBJECTIVE: The aim of this study was to validate the Korean version of the Brief
      Pain Inventory (BPI-K), a pain assessment tool that has been validated in several
      languages. METHODS: The sample consisted of 132 patients in Seoul who had
      recurrent or metastatic cancer and who expressed pain. The Korean version of the
      Beck Depression Inventory (BDI-K), the Eastern Cooperative Oncology Group (ECOG)
      performance status score, the Pain Management Index (PMI), and the PMI-Revised
      (PMI-R) were used to further validate the BPI-K. RESULTS: Cronbach alphas,
      computed for the pain interference and pain severity item, were 0.93 and 0.85,
      respectively. Confirmatory factor analysis of the BPI-K items showed a two-common
      factor solution for the BPI-K, consistently demonstrated in other language
      versions of the BPI. The mean pain interference score was more correlated with
      the BDI-K scale (r = 0.44) and ECOG (r = 0.39) than the mean pain severity score.
      Seventy-four percent of the patients in the Seoul sample had inadequate analgesia
      using the PMI. CONCLUSION: The BPI-K is a valid and useful instrument for
      assessing cancer pain and pain impact in Korea.

PMID- 15452373
TI  - FLEP chemotherapy for alpha-fetoprotein-producing gastric cancer.
AB  - OBJECTIVE: This study aimed at comparing the efficacy of FLEP chemotherapy in the
      treatment of stage IV AFP-producing gastric cancer and stage IV non-AFP-producing
      gastric cancer. METHODS: Between 1989 and 2002, 57 patients with stage IV
      inoperable gastric cancer were given a combination of chemotherapy with 5
      fluorouracil (5-FU), leucovorin (LV), etoposide (VP-16) and cis
      diamminedichloroplatinum (CDDP) (designated as FLEP). In the two groups
      classified histologically according to AFP positivity, the rate of response and
      conversion to surgery, disease-free and overall survival were compared. The
      disease-free and overall survival in the two groups was compared by a log-rank
      test. RESULTS: Patients of the AFP-producing group had a significantly better
      response rate (70 vs. 31.9%, p = 0.03) and a better conversion rate (40 vs.
      12.8%, p = 0.04) than those of the non-AFP-producing group. Patients of the AFP
      producing group also had a significantly better disease-free and overall survival
      (p = 0.02) than those of the non-AFP-producing group. AFP-producing gastric
      cancer was identified as an independent prognostic factor. CONCLUSION: FLEP
      chemotherapy was more effective for stage IV AFP-producing gastric cancer than in
      stage IV non-AFP-producing gastric cancer. Preoperative FLEP chemotherapy
      improved the prognosis of AFP-producing gastric cancer because of downstaging.

PMID- 15452374
TI  - Coexpression of Gas6/Axl in human ovarian cancers.
AB  - OBJECTIVES: Gas6, the protein product of the growth arrest-specific gene 6
      (gas6), a member of the vitamin K-dependent protein family, was identified as a
      ligand for the Axl/Sky family of receptor tyrosine kinases. The aim is to study
      for the presence of Gas6 and its receptor Axl and Sky related to specific growth
      in the ovarian cancers, and to evaluate their plausible growth potential and
      mechanism. METHODS: In ovarian cancers of 90 cases, the histoscores and mRNA
      levels of Gas6, Axl and Sky were determined by immunohistochemistry and
      competitive reverse transcription-polymerase chain reaction-Southern blot
      analysis using the recombinant RNA, respectively. RESULTS: The histoscores and
      mRNA levels of Gas6 and Axl in ovarian cancers were significantly higher than in
      normal ovaries, regardless of histopathological type or clinical stage of ovarian
      cancers. CONCLUSIONS: Gas6/Axl pathway could play a role in the complex events
      taking place during the early changes of ovarian cancer progression.

PMID- 15452375
TI  - Establishment and characterization of a novel human pancreatic cancer cell line
      (SUIT-4) metastasizing to lymph nodes and lungs in nude mice.
AB  - A new tumor cell line (SUIT-4) derived from ascites of a patient with carcinoma
      of the pancreas has been established in tissue culture and in nude mice, and
      maintained for over 7 years. In tissue culture, the cells grew as a confluent
      monolayer with piling up of cells in some areas. The population doubling time
      during the exponential phase of the cell growth was 43.9 h in vitro. Chromosome
      count ranged from 63 to 68 with a modal number of 67. Subcutaneous injection of
      cultured cells into the flanks of nude mice resulted in tumor formation with a
      doubling time of 88.8 h. Histopathologically, xenografts in nude mice were
      moderately differentiated tubular adenocarcinoma, and the tumor cells showed
      spontaneous metastasis to the regional lymph nodes in 6 of 21 nude mice and to
      the lung in 4 of 21. Transmission electron microphotographs confirmed the ductal
      cell origin of the carcinoma and revealed that the cells had abundant
      mitochondria and lysosomes. SUIT-4 cells released carcinoembryonic antigen (3.08
      x 10(2) ng/1 x 10(6) cells/24 h) and carbohydrate antigen 19-9 (4.75 x 10(4) U/1
      x 10(6) cells/24 h) during exponential cell growth in vitro. Reverse
      transcriptase-polymerase chain reaction studies revealed that SUIT-4 cells
      expressed matrix metalloproteinases 1, 3, 7, 10 and 14.

PMID- 15452376
TI  - Valosin-containing protein (p97) and Ki-67 expression is a useful marker in
      detecting malignant behavior of pancreatic endocrine neoplasms.
AB  - OBJECTIVE: To determine the prognostic value of valosin-containing protein (VCP)
      expression and the Ki-67 labeling index (LI) in pancreatic endocrine neoplasms
      (PENs), the present analysis was employed. METHODS: The Ki-67 LI and VCP
      expression at the mRNA and protein level were evaluated in 32 patients (12 male
      and 20 female) with PENs aged from 22 to 73 years (median 49 years). VCP staining
      intensity in tumor cells was categorized as weaker (level 1) or equal to stronger
      (level 2) compared to nontumorous islet cells. Ki-67 LI was divided into two
      categories: level 1, Ki-67 LI < 5%, and level 2, > or = 5%. RESULTS: Five cases
      (15.6%) showed level 1 and 25 (84.4%) level 2 VCP expression by
      immunohistochemistry. A significant association was observed between VCP
      expression and the malignant behavior of PENs (p < 0.01). All level 1 VCP tumors
      were benign PENs. Quantitative reverse transcription polymerase chain reaction
      analysis showed higher VCP mRNA expression in malignant PENs (n = 5) than benign
      cases (n = 5) (p < 0.05). For Ki-67 LI, 28 cases (87.5%) showed level 1 and 4
      (12.5%) level 2 expression. All patients with level 2 Ki-67 LI had metastasis.
      CONCLUSION: VCP expression analysis and Ki-67 LI are useful prognosticators for
      PENs.

PMID- 15452377
TI  - Translocation t(11;18)(q21;q21) is not predictive of response to chemotherapy
      with 2CdA in patients with gastric MALT lymphoma.
AB  - BACKGROUND: t(11;18)(q21;q21) resulting in the API2-MALT1 fusion transcript is an
      exclusive finding in extranodal marginal zone B-cell lymphoma of mucosa
      associated lymphoid tissue (MALT lymphoma). While it has recently been
      demonstrated as a negative predictor for gastric MALT lymphoma undergoing
      eradication of Helicobacter pylori, nothing is known about the relation between
      t(11;18)(q21;q21) status and response to chemotherapy. We have therefore
      performed a retrospective analysis of t(11;18)(q21;q21) in patients undergoing
      chemotherapy with the nucleoside analogue cladribine (2CdA) for gastric MALT
      lymphoma. PATIENTS AND METHODS: Eighteen cases of gastric MALT lymphoma treated
      with 2CdA were reviewed, and 17 could be investigated for t(11;18)(q21;q21) by
      reverse-transcription polymerase chain reaction and fluorescence in situ
      hybridization. t(11;18)(q21;q21) was correlated with response to chemotherapy.
      RESULTS: Of the 17 patients with gastric MALT lymphoma treated with 2CdA, 9 were
      at stage IE, 2 at stage IIE and 6 at stage IV. Eight cases with stage IE lymphoma
      were first treated with H. pylori eradication, but none of them showed
      histological regression during a minimum follow-up of 12 months, and they were
      subsequently treated with primary chemotherapy. One patient received chemotherapy
      due to absence of H. pylori infection. Another patient initially rated as stage
      IE whose gastric lymphoma did not respond developed spread to the lung during
      follow-up after eradication. All the remaining 13 cases were treated by
      chemotherapy at the time of diagnosis. Out of these 17, 8 patients (47%) were
      found to carry t(11;18)(q21;q21). One patient, who was negative for
      t(11;18)(q21;q21), progressed during chemotherapy and died 5 months after
      initiation of treatment. One patient each with and without t(11;18)(q21; q21) had
      a partial response lasting for 14 and >18 months, respectively. One
      t(11;18)(q21;q21)-positive patient had stable disease for >16 months. The
      remaining patients achieved a complete remission (CR) following treatment; 6 were
      positive for t(11;18)(q21;q21), while the remaining 6 were negative. Two patients
      [1 positive and 1 negative for t(11;18)(q21;q21), respectively] have developed a
      local relapse following CR and were salvaged by radiotherapy. CONCLUSION: Our
      findings suggest that the presence of the API2-MALT1 fusion transcript resulting
      from t(11;18)(q21;q21) does not adversely affect the response of gastric MALT
      lymphoma to chemotherapy with 2CdA. 2CdA appears to be an attractive agent for
      treatment of gastric MALT lymphoma unresponsive to H. pylori eradication,
      including those positive for t(11;18)(q21;q21).

PMID- 15452378
TI  - Cell growth inhibition and gene expression induced by the histone deacetylase
      inhibitor, trichostatin A, on human hepatoma cells.
AB  - OBJECTIVE: Histone deacetylase (HDAC) inhibitors have been reported to induce
      cell growth arrest, apoptosis and differentiation in tumor cells. The effect of
      the HDAC inhibitor, trichostatin A (TSA), on hepatoma cells, however, has not
      been well studied. In this study, we examined cell viability and gene expression
      profile in hepatoma cell lines treated with TSA. METHODS: To study cell growth
      inhibition and induction of apoptosis by TSA on human hepatoma cell lines
      including HuH7, Hep3B, HepG2, and PLC/PRF/5, cells were treated with TSA at
      various concentrations and analyzed by the 3-(4, 5-dimethyl-2-thiazolyl)-2H
      tetrazolium bromide (MTT) and TUNEL assays, respectively. Changes in gene
      expression profile after exposure to TSA were assessed using a cDNA microarray
      consisting of 557 distinct cDNA of cancer-related genes. The levels of acetylated
      histones were examined by the chromatin immunoprecipitation (ChIP) assay using
      anti-acetylated histone H3 or H4 antibody. RESULTS: The MTT assay demonstrated
      that TSA showed cell growth inhibition not only in a concentration-dependent but
      also a time-dependent manner on all cell lines studied. The TUNEL assay also
      revealed the potential of TSA to induce apoptosis. The microarray analysis
      revealed that 8 genes including collagen type 1, alpha2 (COL1A2), insulin-like
      growth factor binding protein 2 (IGFBP2), integrin, alpha7 (ITGA7), basigin
      (BSG), quiescin Q6 (QSCN6), superoxide dismutase 3, extracellular (SOD3), nerve
      growth factor receptor (NGFR), and p53-induced protein (PIG11) exhibited
      substantial induction (ratio >2.0) after TSA treatment in multiple cell lines.
      ChIP assay, in general, showed a good correlation between the expression level of
      mRNA and levels of acetylated histones in these upregulated genes. CONCLUSIONS:
      This study showed cell growth inhibition and the gene expression profile in
      hepatoma cell lines exposed to TSA. The alteration in levels of acetylated
      histones was closely associated with expression of specific cancer-related genes
      in hepatoma cells.

PMID- 15452379
TI  - Attachment of human colon cancer cells to vascular endothelium is enhanced by N
      acetylglucosaminyltransferase V.
AB  - Expression of N-acetylglucosaminyltransferase V (GnT-V) in colon cancer has been
      shown to be related to hematogenous metastasis and poor prognosis. To investigate
      the mechanism by which cancer cells expressing GnT-V metastasize to distant
      organs, we established GnT-V-overexpressing DLD-1 and WiDr cells (human colon
      cancer cell lines) by transfecting them with a GnT-V expression vector.
      Attachment to endothelial cells expressing E-selectin was studied, and expression
      of the E-selectin ligand, sialyl Lewis x, in colon cancer cells was investigated.
      Both of the cell lines showed reduced adhesion to fibronectin as compared with
      mock transfectants. In contrast, attachment to human umbilical vein endothelial
      cells expressing E-selectin was significantly enhanced by GnT-V expression (p <
      0.01). Sialyl Lewis x is a ligand for E-selectin and a marker for poor prognosis
      of colon cancer. Its synthesis in cells has been shown to involve GnT-V. We
      demonstrated that expression of sialyl Lewis x in colon cancer cells was induced
      by GnT-V expression. These results suggest that GnT-V induces sialyl Lewis x
      expression and leads colon cancer cells to metastasize by enhancing their ability
      to attach to vascular endothelium in distant organs, such as liver or lung.
      Inhibition of GnT-V activity may prevent metastasis in colon cancer patients with
      high sialyl Lewis x expression.

PMID- 15452380
TI  - Clear cell renal cell carcinoma associated with bilateral atypical acute
      posterior multifocal placoid pigment epitheliopathy.
AB  - BACKGROUND/OBJECTIVE: Clear cell renal cell carcinoma (CCRCC) is a malignant
      neoplasm frequently associated with an increase in circulating immune complexes
      (CIC). Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) is a
      disease involving the chorioretinal structures of the eye, and it is commonly
      observed in association with several immunogenic disorders. We report here the
      clinical association between humoral immunologic modifications during tumoral
      diseases (long-standing CIC increase) and chorioretinal changes resembling
      atypical APMPPE. CASE REPORT: A 52-year-old white male affected by metastatic
      CCRCC is described. Histopathologic review of his surgically removed organs
      (kidney and lung), periodical laboratory immunologic tests and ophthalmologic
      examinations, including fluorescein and indocyanine green angiographies, were
      performed. RESULTS: The patient underwent total left nephrectomy (May 1997) and
      total left pneumonectomy (March 2001) for the presence of stage III CCRCC and
      CCRCC lung metastasis, respectively. On both occasions, postoperative
      immunotherapy was started. From June 1997 to February 2003, laboratory analyses
      demonstrated the presence of marked CIC peaks. During the follow-up period, an
      atypical APMPPE pattern, complicated by asynchronous choroidal
      neovascularization, occurred in both eyes. CONCLUSIONS: Long-standing tumorous
      disease, through a pathogenic mechanism triggered by CIC spreading, can be
      responsible, over time, for a progressive choroidal occlusive microangiopathy
      (atypical APMPPE pattern), associated with a high risk of poor visual outcome.
      Therefore, bilateral APMPPE could be related to a systemic disease able to
      increase CIC levels.

PMID- 15452381
TI  - 5-Fluorouracil-induced coronary spasm: may inhibition of hyperpolarization
      factors produced by CYP2C enzymes be the cause?

PMID- 15452382
TI  - Raynaud's phenomenon and endothelial dysfunction in end-stage renal disease
      patients treated with hemodialysis.
AB  - BACKGROUND/AIMS: Steal syndrome is a well-known complication of arteriovenous
      shunt placement. Increased frequency of Raynaud's phenomenon (RP) especially
      concerning shunt limb is reported among hemodialysis (HD) patients. The aim of
      the study was to assess the relation of impairment of peripheral circulation
      diagnosed with cold stress test (CST) and thermography to the AV shunt location
      and markers of endothelial dysfunction in HD patients. METHODS: The study group
      comprised 21 patients (6 male, 15 female, mean age 32.6 +/- 15.0 years) treated
      with HD for a mean of 69 +/- 54 months. 10 healthy individuals (4 male, 6 female,
      mean age 38.6 +/- 14.7 years) served as controls. The diagnosis of RP was made
      upon the results of thermographic measurements during CST. Von Willebrand factor
      activity and antigen, endothelin-1 and plasma total homocysteine (tHcy) were
      measured in all subjects. RESULTS: RP was found significantly more often in HD
      patients than in controls: 11/21 vs. 1/10 (p = 0.04). RP occurred in both hands
      in 7/11 (64%) patients. tHcy was higher in HD patients than in the controls (31.7
      +/- 13.9 vs. 10.9 +/- 3.2 microg/l, p < 0.0001). tHcy and von Willebrand factor
      antigen were significantly higher in the RP-positive than RP-negative patients or
      controls. CONCLUSION: Small vessel dysfunction diagnosed as positive RP is a
      frequent finding in HD patients. It seems that endothelial injury rather than AV
      shunt steal syndrome is responsible for development of RP in HD patients.

PMID- 15452383
TI  - Angiotensin II receptor modulation of renal vascular resistance and
      neurotransmission in young and adult spontaneously hypertensive rats.
AB  - BACKGROUND/AIMS: Angiotensin (Ang) II modulates vascular resistance and
      sympathetic neurotransmission through Ang II type 1 (AT1) receptors. Recent
      studies reported an involvement of AT2 receptors. We investigated whether AT2
      receptors participate in modulation of vascular resistance and sympathetic
      neurotransmission in spontaneously hypertensive rats (SHR). METHODS: Kidneys of 6
      and 16-week-old normotensive (WKY) and SHR were isolated and perfused. RESULTS:
      Noradrenaline release induced by renal nerve stimulation (RNS) was increased in
      SHR (WKY: 1,837 +/- 128, SHR: 2,310 +/- 192 pg/g). Ang I- and II-induced pressor
      responses and enhancement of noradrenaline release were greater in SHR than in
      WKY. Pressor responses to Ang I and II were greater in adult compared with young
      SHR. The AT1 receptor antagonist EXP3174 (0.1 microM) blocked Ang I- and II
      induced renal vasoconstriction and noradrenaline release to RNS in both strains.
      In contrast, the selective AT2 receptor antagonist PD 123319 (1 microM) had no
      influence in young and adult WKY and SHR. CONCLUSION: Ang I and II had a greater
      impact on renal vascular resistance and neurotransmission in SHR, which was more
      pronounced in adult SHR. All effects are mediated by the AT1 receptor and no
      modulatory influence of the AT2 receptor could be found.

PMID- 15452384
TI  - Hypokalemia and alkalosis in adipsic hypernatremia are not associated with
      hyperaldosteronism.
AB  - Idiopathic adipsic hypernatremia (AH) is a rare disorder associated with
      hypokalemia and alkalosis. Hypokalemic alkalosis has been presumed to be
      secondary to hyperaldosteronism. We evaluated plasma renin activity, serum
      aldosterone, serum and urine electrolytes in a 17-year-old patient with AH on
      several occasions. Despite evidence of mild dehydration, serum Na >160 and K
      <3.2, aldosterone levels were suppressed and plasma renin activity was not
      elevated. Urine Na and K were not conserved. We also examined electrolyte and
      hormone levels in previously reported cases of AH. Aldosterone levels were not
      increased in any of the cases when measured. Renin secretion was increased in 2
      patients. Among the compiled cases serum K was inversely correlated with serum Na
      (r = -0.73, p < 0.002, n = 15). Hypokalemia and alkalosis occurring in AH are not
      associated with secondary hyperaldosteronism. Patients with AH may have chronic
      renal losses of potassium leading to hypokalemia and alkalosis.

PMID- 15452385
TI  - Genotype-phenotype correlation in patients suspected of having Sotos syndrome.
AB  - BACKGROUND: Deletions and mutations in the NSD1 gene are the major cause of Sotos
      syndrome. We wanted to evaluate the genotype-phenotype correlation in patients
      suspected of having Sotos syndrome and determine the best discriminating
      parameters for the presence of a NSD1 gene alteration. METHODS: Mutation and
      fluorescence in situ hybridization analysis was performed on blood samples of 59
      patients who were clinically scored into 3 groups. Clinical data were compared
      between patients with and without NSD1 alterations. With logistic regression
      analysis the best combination of predictive variables was obtained. RESULTS: In
      the groups of typical, dubious and atypical Sotos syndrome, 81, 36 and 0% of the
      patients, respectively, showed NSD1 gene alterations. Four deletions were
      detected. In 23 patients (2 families) 19 mutations were detected (1 splicing
      defect, 3 non-sense, 7 frameshift and 8 missense mutations). The best predictive
      parameters for a NSD1 gene alteration were frontal bossing, down-slanted
      palpebral fissures, pointed chin and overgrowth. Higher incidences of feeding
      problems and cardiac anomalies were found. The parameters, delayed development
      and advanced bone age, did not differ between the 2 subgroups. CONCLUSIONS: In
      our patients suspected of having Sotos syndrome, facial features and overgrowth
      were highly predictive of a NSD1 gene aberration, whereas developmental delay and
      advanced bone age were not.

PMID- 15452386
TI  - Partial androgen insensitivity syndrome and t(X;5): are there upstream regulatory
      elements of the androgen receptor gene?
AB  - BACKGROUND/AIMS: Two half-brothers with similar malformed genitals, who both
      inherited a maternally derived t(X;5)(q13;p15) translocation, have a phenotype
      consistent with partial androgen sensitivity syndrome. The aim was to identify
      the gene disrupted by the X chromosome breakpoint. METHODS: The breakpoint was
      localized using fluorescence in situ hybridization to metaphase spreads of the
      translocation. RESULTS: The breakpoint on the X chromosome of the X;5
      translocation was localized to a 30-kb region. This region does not contain any
      identified genes or transcripts. However, the breakpoint is approximately 134 kb
      from the 5' end of the androgen receptor (AR) gene. CONCLUSIONS: Genetic defects
      of the AR gene are collectively called androgen insensitivity syndrome and
      include a range of phenotypes from normal males, often with associated sterility,
      to XY females. The phenotype seen in the males with the t(X;5) is consistent with
      this syndrome. The analysis of the chromosomal abnormality suggests that this
      translocation may remove one or more upstream regulatory elements of the AR gene
      that are essential for its normal expression and its role in typical external
      masculinization.

PMID- 15452387
TI  - A tale of medical shopping or the hazards of repetitious cytological screening of
      the cervix.
AB  - A 65-year-old woman had on her own initiative three cervical smears taken at very
      short intervals. The second smear was taken only 1 day after the first one. It
      contained necrotic cellular material with atypia due to the scraping on the day
      before; it was at first mistakenly interpreted as showing malignant features.
      This led to the performance of various diagnostic procedures, and a considerably
      greater cost for the medical insurance system.

PMID- 15452388
TI  - Do the recently modified pacemaker guidelines for neurocardiogenic syncope also
      apply to young patients? Analysis based on five-year follow-up of israeli
      soldiers with syncope and a positive tilt test.
AB  - To assess the classification of neurocardiogenic syncope (NCS) as a IIA
      indication for pacemaker implantation in the recent American College of
      Cardiology/American Heart Association Task Force on Practice Guidelines/North
      American Society for Pacing and Electrophysiology guidelines, we performed chart
      reviews and follow-up interviews in a cohort of 45 consecutive young Israeli
      soldiers (age 18-24 years) with a history of syncope (mean of 9 prior syncopal
      episodes) and a positive tilt test treated with drug therapy. Asystole longer
      than 5 s during tilt testing occurred in 11 patients. Five years later, we found
      that only 2 patients were still taking medications, only 1 patient (2%) still
      reported frequent syncopal or near-syncopal episodes and 3 patients (7%) had rare
      symptoms (no more than one syncopal episode during the past 2 years), while the
      remaining 40 (89%) were symptom free off medications. Thus, NCS in young
      patients, even with prolonged asystole during tilt testing, a history of frequent
      syncopal episodes and other high- risk factors described in the guidelines, is
      often a self-limiting disorder, perhaps stress related or situational in nature;
      an overwhelming number of patients become asymptomatic and stop taking
      medications within 1-2 years. These patients do not require long-term therapy;
      thus, our data would suggest that the IIA pacing indication for NCS should be
      restricted to older patients.

PMID- 15452389
TI  - Lower limb compression bandaging is effective in preventing signs and symptoms of
      seating-induced postural hypotension.
AB  - BACKGROUND AND AIMS: Data concerning postural hypotension (PH) induced by
      transition from supine to sitting position are scarce and measures for its
      prevention have not been investigated. Our objective was to assess the preventive
      role of lower limb compression bandaging on PH and associated manifestations in
      older inpatients when seated from lying position. METHODS: In a randomized
      crossover study, 61 patients aged >65 years were enrolled. Following bed rest
      lasting >36 h, each patient was seated and studied for 2 consecutive days,
      unbandaged or bandaged. PH was defined as a fall of >/=20 mm Hg and/or >/=10 mm
      Hg in systolic/diastolic blood pressure, respectively. Compression bandages were
      applied along both legs before seating; the pressure was approximately 30 mm Hg.
      Blood pressure, heart rate, O(2) saturation, dizziness and palpitations were
      recorded prior to and 1, 3, and 5 min following seating. RESULTS: Prevalence of
      PH was identical in the unbandaged versus bandaged state (55.7%). However,
      dizziness, palpitations, accelerated heart rate and decreased O(2) saturation
      over 5 min were more prevalent in the unbandaged versus bandaged state (p < 0.01,
      <0.001, <0.05, <0.001, respectively). In the unbandaged state, presence versus
      absence of PH was associated with significantly greater incidence of
      palpitations, tachycardia and decline of O(2) saturation over time (p < 0.04,
      <0.03, <0.03, respectively). In the bandaged state, O(2) saturation over 5 min
      tended to rise irrespective of PH, but mean values were higher in patients
      without PH (p < 0.02). CONCLUSIONS: Lower limb compression bandaging does not
      reduce the incidence of PH. However, associated manifestations are largely
      prevented.

PMID- 15452390
TI  - Glycoprotein IIb/IIIa inhibitor-associated thrombocytopenia: clinical predictors
      and effect on outcome.
AB  - Glycoprotein IIb/IIIa inhibitors are used as an adjunct to antiplatelet therapy
      in percutaneous coronary intervention to reduce postprocedural enzyme elevations.
      Previous studies have shown a risk for thrombocytopenia that is associated with
      these agents. We sought to evaluate the incidence and outcomes of glycoprotein
      IIb/IIIa inhibitor-associated thrombocytopenia in an unselected series of
      patients undergoing percutaneous coronary intervention. We reviewed 984
      interventions performed on 908 subjects over a specific time period. Glycoprotein
      IIb/IIIa inhibitors were used in 58.8% of cases. Their use increased from 38 to
      82% during the study period (p < 0.0001). The incidence of glycoprotein IIb/IIIa
      inhibitor-associated thrombocytopenia was 5.4%. The occurrence of
      thrombocytopenia was not associated with higher age, gender or ethnicity. The
      preprocedural platelet count was not associated with induced thrombocytopenia
      (237 +/- 76 vs. 209 +/- 68 x 10(3), p > 0.05). The occurrence of thrombocytopenia
      was not associated with increased in-hospital mortality, 1-year mortality,
      myocardial infarction or revascularization, but was associated with a hospital
      stay twice as long as in those patients without thrombocytopenia (5.6 +/- 11.3
      vs. 2.1 +/- 2.2 days, p < 0.001). Of the 5.4% of patients who developed
      thrombocytopenia, only 2 patients (7.1%) required platelet or blood cell
      transfusion.

PMID- 15452391
TI  - Brain natriuretic peptide levels fall rapidly after cardioversion of atrial
      fibrillation to sinus rhythm.
AB  - BACKGROUND: Brain natriuretic peptide (BNP) levels have been reported to fall
      following cardioversion of atrial fibrillation (AF). The mechanism for the fall
      in BNP has not been elucidated and the potential confounding effects of sedation
      have not been investigated. Sedation may alter BNP levels via its effects on
      loading conditions. Accordingly, we studied whether BNP levels change shortly
      after cardioversion and attempted to control for possible effects of sedation.
      METHODS: BNP levels were obtained before and after cardioversion in patients with
      AF and in a control group of patients undergoing intravenous conscious sedation
      for transesophageal echocardiography. RESULTS: BNP levels dropped (260 +/- 255
      vs. 190 +/- 212 pg/ml, p < 0.05) 40 min after cardioversion, decreasing in 33 of
      41 subjects who achieved sinus rhythm. By contrast, mean BNP did not fall in
      subjects in whom cardioversion was not successful. The change in BNP level was
      not related to the degree of change in heart rate. No control subject experienced
      a change in cardiac rhythm; BNP levels increased (195 +/- 407 vs. 238 +/- 458
      pg/ml, p < 0.05) in 18/22 subjects after sedation. Baseline BNP levels were
      elevated in subjects with AF, and BNP levels were elevated in parallel with heart
      failure symptoms. CONCLUSIONS: The rapid fall in BNP after cardioversion (1) may
      reflect prompt hemodynamic improvement associated with rhythm change and (2) does
      not appear to be due to the effects of sedation.

PMID- 15452392
TI  - Diurnal variation of soluble E- and P-selectin, and intercellular adhesion
      molecule-1 in patients with and without coronary artery disease.
AB  - BACKGROUND: The more frequent onset of acute coronary syndromes (ACS) in the
      morning has been known for a long time. Diurnal changes of fibrinolysis such as
      lower activity of tissue plasminogen activator and higher activity of plasminogen
      activator inhibitor-1 (PAI-1) in the morning has been demonstrated previously and
      correspond with the manifestation of ACS. Less is known about the diurnal
      variation of soluble adhesion molecules as markers of endothelial or platelet
      activity in patients with coronary artery disease (CAD). PATIENTS AND METHODS: 80
      patients with a history of myocardial infarction and/or chest pain with positive
      exercise testing admitted for elective coronary angiography were studied. 10 had
      normal findings on coronary angiography (control group), 70 patients had at least
      one or more stenoses >/=50% of the diameter of an epicardial vessel. None of the
      patients suffered from acute inflammation, connective or tumor disease. Blood
      samples were drawn at 7:00 a.m. and at 7:00 p.m. at rest and plasma concentration
      of soluble P-selectin (sP-selectin), E-selectin (sE-selectin), intercellular
      adhesion molecule-1 (sICAM-1) and acute-phase proteins were measured by ELISA.
      RESULTS: In both groups, no diurnal variation was found in sE-selectin and sICAM
      1. sP-selectin levels were significantly higher in the evening (CAD group: 149.8
      +/- 54.5 vs. 172.2 +/- 68.8 ng/ml, p < 0.001; control: 148.7 +/- 75.5 vs. 187.5
      +/- 96.3 ng/ml, p = 0.001, Wilcoxon test). CONCLUSION: We have demonstrated
      diurnal variation of sP-selectin in patients with CAD. We conclude that high sP
      selectin values in the evening represent the shed forms of the morning membrane
      bound P-selectin.

PMID- 15452393
TI  - Effects and safety of intracoronary thrombectomy using transradial application of
      the PercuSurge distal balloon protection system in patients with early or recent
      myocardial infarction.
AB  - BACKGROUND: Distal embolization and no reflow are likely during primary
      percutaneous coronary intervention (PCI) on the large infarct-related artery
      (IRA), which mostly contains high-burden thrombus formation (HBTF) and plaque
      burden. Mechanical devices to prevent distal atheroembolism may be of importance
      for preserving reperfusion and microvascular integrity in IRA. METHODS AND
      RESULTS: Between May 2002 and December 2002, transradial application (TRA) of the
      PercuSurge GuardWire device with 7-french arterial sheath was performed in 39
      consecutive patients who experienced early (>12 h and </=7 days) or recent (>7
      days and <14 days) myocardial infarction (MI) associated with large IRA (vessel
      size >/=3.5 mm with HBTF; group 1). Between January 2001 and April 2002, 64
      consecutive patients who had early or recent MI associated with HBTF in IRA of a
      vessel size >/=3.5 mm received TRA of PCI with adjunctive tirofiban therapy but
      without using the adjunctive PercuSurge GuardWire device (group 2). The
      angiographic and clinical outcomes of both groups were compared in a
      chronologically consecutive manner. The procedural success rate and post-PCI
      myocardial blush grades were significantly higher in group 1 than in group 2
      patients (all p values <0.05), whereas a combined incidence of vascular and
      bleeding complications and 30-day major adverse cardiac events (defined as death,
      reinfarction and repeated PCI of IRA) were significantly higher in group 2 than
      in group 1 patients (all p values <0.05). CONCLUSIONS: Our data suggested that
      TRA using the PercuSurge GuardWire device during PCI for patients with early or
      recent MI and HBTF in IRA was safe and feasible. This mechanical device provided
      more additional benefit to patients in this clinical setting than a combination
      of conventional PCI and tirofiban therapy.

PMID- 15452394
TI  - Clinical association between renal insufficiency and positive troponin I in
      patients with acute coronary syndrome.
AB  - BACKGROUND: Whether renal insufficiency (RI) influences troponin levels in
      patients with acute coronary syndromes (ACS) is controversial. We attempted to
      determine whether there is an association between RI and troponin I (TnI)
      elevation in patients presenting with ACS. METHODS: We studied 764 consecutive
      patients with ACS admitted to our institution from January 1999 to June 2000.
      Patients were identified prospectively and data were collected through chart
      review of all cases with an admission diagnosis of ACS. In order to assess the
      relationship of TnI and RI, we calculated the creatinine clearance (Cr-Cl) for
      all patients. We conducted an analysis of variance comparing TnI in quintiles of
      patients with lowest to highest Cr-Cl. RESULTS: Among 764 patients, 173 patients
      had a discharge diagnosis of ST elevation myocardial infarction and 591 had non
      ST elevation myocardial infarction. There was no correlation between peak TnI
      levels and renal function as measured by Cr-Cl in the entire cohort with ACS and
      in the subgroups with ST elevation myocardial infarction and non ST elevation
      myocardial infarction. CONCLUSIONS: This large cohort study demonstrates that
      there appears to be no association between RI and positive TnI in patients with
      ACS.

PMID- 15452395
TI  - Color Doppler tissue velocity imaging demonstrates significant asynchronous
      regional left ventricular contraction and relaxation in patients with bundle
      branch block and heart failure compared with control subjects.
AB  - Bundle branch block in patients with severe heart failure (HF) may result in
      asynchronous regional left ventricular (LV) contraction. Colour Doppler tissue
      velocity imaging (c-TVI) allows tissue velocity profiles to be measured with a
      resolution of 10 ms. Normal subjects (n = 30) showed a synchronous regional
      longitudinal LV pattern of movement, and HF patients with bundle branch block (n
      = 30) showed asynchronous contraction and relaxation patterns which were
      quantified by c-TVI as ranging from -22 to 19 ms. This asynchronous LV
      contraction probably contributes to the deterioration of LV function in HF
      patients.

PMID- 15452396
TI  - Acquired left ventricular hypertrabeculation/noncompaction in mitochondriopathy.

PMID- 15452397
TI  - Recurrent thrombophlebitis in a colon cancer patient with C677T heterozygous
      genotype for MTHFR treated with 5-fluorouracil-based adjuvant chemotherapy.

PMID- 15452398
TI  - Activity of nadifloxacin (OPC-7251) and seven other antimicrobial agents against
      aerobic and anaerobic Gram-positive bacteria isolated from bacterial skin
      infections.
AB  - BACKGROUND AND METHODS: The in vitro activity of nadifloxacin (OPC-7251), a novel
      topical fluoroquinolone, was assessed and compared with those of ofloxacin,
      oxacillin, flucloxacillin, cefotiam, erythromycin, clindamycin, and gentamicin
      against 144 Gram-positive bacteria: 28 Staphylococcus aureus, 10 Streptococcus
      spp., 68 coagulase-negative staphylococci (CNS), 36 Propionibacterium acnes, and
      2 Propionibacterium granulosum strains. All strains originated from bacterial
      infected skin disease and were isolated from patients with impetigo, secondary
      infected wounds, folliculitis and sycosis vulgaris, and impetiginized dermatitis.
      In vitro susceptibility of all clinical isolates was tested by agar dilution
      procedure and minimum inhibitory concentrations (MICs) were determined. RESULTS:
      Nadifloxacin was active against all aerobic and anaerobic isolates. MIC(90) (MIC
      at which 90% of the isolates are inhibited) was 0.1 microg/ml for S. aureus, 0.78
      microg/ml for both Streptococcus spp. and CNS, and 0.39 microg/ml for
      Propionibacterium spp. On the other hand, resistant strains with MICs exceeding
      12.5 mug/ml were found in tests with the other antibiotics. For both CNS and
      Propionibacterium acnes, MIC(90) values > or =100 microg/ml were demonstrated for
      erythromycin. Ofloxacin, cefotiam, erythromycin, clindamycin and gentamicin
      exhibited MIC(90) values < or =1 microg/ml for some bacterial species tested.
      Both oxacillin and flucloxacillin were active against all investigated bacterial
      species with MIC(90) values < or =1 microg/ml. CONCLUSION: In summary,
      nadifloxacin, a topical fluoroquinolone, was found to be highly active against
      aerobic and anaerobic bacteria isolated from patients with infected skin disease,
      and seems to be a new alternative for topical antibiotic treatment in bacterial
      skin infections.

PMID- 15452399
TI  - Activity of levofloxacin and ciprofloxacin in combination with cefepime,
      ceftazidime, imipenem, piperacillin-tazobactam and amikacin against different
      Pseudomonas aeruginosa phenotypes and Acinetobacter spp.
AB  - BACKGROUND: Combination therapy is used to widen the antimicrobial spectrum,
      minimize toxicity and prevent the emergence of resistant mutants. METHODS:
      Synergy between levofloxacin or ciprofloxacin and ceftazidime, cefepime,
      imipenem, piperacillin-tazobactam and amikacin was evaluated by checkerboard
      assay with 55 strains and by time-kill curves with 8 strains of Pseudomonas
      aeruginosa and Acinetobacter spp. RESULTS: In the checkerboard assay, synergy and
      additivity were the most frequent effects observed among all the combinations
      against P. aeruginosa and Acinetobacter spp., with no significant differences
      between the two fluoroquinolones. No antagonism was observed. In the time-kill
      curves, synergy was evidenced against all the tested strains, at least for one
      combination at one of the time points considered. Levofloxacin and ciprofloxacin
      combined with ceftazidime, as well as levofloxacin plus amikacin, were
      synergistic for all the strains tested. CONCLUSION: Combinations of
      fluoroquinolones with beta-lactams or amikacin show an enhanced activity against
      P. aeruginosa and Acinetobacter spp.

PMID- 15452400
TI  - Resuscitation of depressed newborn infants with ambient air or pure oxygen: a
      meta-analysis.
AB  - BACKGROUND: It is discussed whether depressed newborn infants should be
      resuscitated with room air or 100% O2. OBJECTIVE: To perform a systematic review
      and meta-analysis including studies that report resuscitation of depressed newly
      born infants with 21 or 100% O2. METHODS: Inclusion criterion was randomized or
      pseudo-randomized, blinded or not, studies of depressed newborn infants
      resuscitated with either 21 or 100% O2. The literature was searched in
      Medline/Pubmed/EMBASE and The Cochrane library databases. All identified studies
      were included. RESULTS: Five studies fulfilled the inclusion criterion in which
      881 infants were resuscitated with 21% O2 and 856 with 100% O2. Neonatal
      mortality was 8.0 vs. 13.0% in the 21 and 100% O2 groups respectively, OR 0.57,
      95% CI 0.42-0.78. In term infants neonatal mortality was 5.9% in the 21% O2 group
      and 9.8% in the 100% O2 group, OR 0.59, 95% CI 0.40-0.87. The figures for the
      premature infants were very similar. In infants with 1-min Apgar score <4, OR for
      neonatal mortality was 0.81 (95% CI 0.54-1.21). Apgar score at 5 min and heart
      rate at 90 s were significantly higher, and time to first breath significantly
      earlier in infants given 21% O2 compared with 100% O2. CONCLUSIONS: A systematic
      review and meta-analysis demonstrated that neonatal mortality is significantly
      reduced when depressed newly born infants are resuscitated with ambient air
      instead of pure oxygen. For infants with low 1-min Apgar score (<4), no
      significant difference in neonatal mortality was found. Recovery was faster in
      infants resuscitated with 21% O2 than 100% O2.

PMID- 15452401
TI  - Malanga (Xanthosoma sagittifolium) and purslane (Portulaca oleracea) leaves
      reduce oxidative stress in vitamin A-deficient rats.
AB  - AIM: This study examined the ability of tropical vegetables to reduce oxidative
      stress induced by vitamin A deficiency. METHODS: Vitamin A-deficient male Wistar
      rats were divided into four groups which were treated for 30 days with different
      diets: AIN-93G vitamin A-deficient diet (DD), DD supplemented with pure beta
      carotene (beta-D) and DD supplemented with malanga (Xanthosoma sagittifolium)
      (MD) or purslane (Portulaca oleracea) (PD) leaves as the only source of vitamin
      A. The thiobarbituric acid-reactive substances (TBARS), reduced (GSH) and
      oxidized (GSSG) glutathione, and antioxidant enzyme activities were determined in
      the heart and liver. RESULTS: The rats fed beta-D, MDand PD showed liver and
      heart TBARS concentrations lower than did DD rats. The liver GSH concentration of
      beta-D, MD and PD rats was lower compared to DD rats. The heart GSSG
      concentration of the vegetable groups was significantly lower than in DD rats.
      Liver and heart catalase activities were not significantly different among the
      groups, nor was heart glutathione peroxidase (GPX) activity, however the beta-D
      rats showed the highest liver GPX activity. There was no difference in liver
      glutathione-S-transferase level among the groups, while heart activity was higher
      in rats fed the vegetable leaves. CONCLUSION: This study evidences that the
      ingestion of purslane or malanga leaves may have a protective effect against
      oxidative stress caused by vitamin A deficiency.

PMID- 15452402
TI  - Physiological and chronobiological changes during Ramadan intermittent fasting.
AB  - BACKGROUND AND AIMS: During the month of Ramadan, Moslems refrain from drinking
      and eating between sunrise and sunset. This review aimed to analyze the effects
      of Ramadan fasting on physiological and behavioral variables in healthy subjects.
      METHODS: Articles included in this paper were taken from Medline, three
      international congresses on health and Ramadan, and in several cases from local
      journals. RESULTS: Ramadan fasting did not dramatically affect the metabolism of
      lipids, carbohydrates and proteins, or the daily mean of hormonal serum levels.
      An increase in serum urea and uric acid was frequently reported and this could be
      attributed to dehydration during this month. Some changes, such as the increase
      of HDL and apoprotein A1, and the decrease in LDL, could be beneficial for the
      cardiovascular system. However, the chronobiological studies have shown that
      Ramadan fasting affects the circadian distribution of body temperature, cortisol,
      melatonin and glycemia. The amplitude of most of these rhythms decreased and the
      acrophase shifted. Nocturnal sleep, daytime alertness and psychomotor performance
      were decreased. CONCLUSION: The major changes during Ramadan fasting are
      chronobiological and behavioral. They could be responsible for the high incidence
      of road traffic accidents and the reduction of working hours during the month of
      Ramadan.

PMID- 15452403
TI  - Vitamin D insufficiency and deficiency in chronic kidney disease. A single center
      observational study.
AB  - BACKGROUND: Kidney disease has been identified as a risk factor for vitamin D
      deficiency in hospitalized patients, and low levels of 25-hydroxyvitamin D have
      been suggested to be a risk factor for hyperparathyroidism in patients with
      chronic kidney disease (CKD). However, little is known about the magnitude of
      vitamin D deficiency in patients with CKD living in the United States. METHODS:
      In this regard, we examined the levels of 25(OH)D in 43 patients with CKD and
      serum creatinine between 1 and 5 mg/dl (calculated glomerular filtration rate 111
      11 ml/min per 1.73 m2) as well as in 103 patients undergoing hemodialysis.
      RESULTS: In the predialysis patients, we found that 37 of the 43 patients (86%)
      had suboptimal levels of vitamin D (<30 ng/ml). Regression analysis indicated
      that there was a negative correlation between 25(OH)D and intact parathyroid
      hormone (PTH). Alkaline phosphatase showed a similar but less sensitive
      relationship. Serum albumin levels correlated with 25(OH)D levels. In contrast to
      findings reported in normal individuals, the levels of calcitriol correlated with
      those of 25(OH)D in the patients with CKD. In the group undergoing maintenance
      hemodialyis, we found that 97% of the patients had vitamin D levels in the
      suboptimal range, and there was no correlation of 25(OH)D levels with either PTH
      or serum albumin values. These data indicate that vitamin D insufficiency and
      deficiency are highly prevalent in patients with CKD and may play a role in the
      development of hyperparathyroidism. The functional significance of low levels of
      25(OH)D in patients with stage 5 CKD remains to be determined.

PMID- 15452404
TI  - Dialyzing a patient with human immunodeficiency virus infection: what a
      nephrologist needs to know.
AB  - The percentage of dialysis centers that have reported dialyzing human
      immunodeficiency virus (HIV)-infected patients increased from 11% in 1985 to 37%
      in 2000. Being primary care physicians for the dialysis patients, nephrologists
      are frequently confronted with the management of HIV-infected dialysis patients
      especially in urban centers. The aims of the present review are to discuss issues
      that are unique to HIV infection and end-stage renal disease, and to provide
      dialysis caretakers with sufficient information to help them optimize care and
      improve outcomes of these patients. Issues related to the choice of renal
      replacement therapy, vascular access, management of anemia, vaccination, and
      antiretroviral therapies are discussed in detail.

PMID- 15452405
TI  - Anemia and diabetes.
AB  - World Health Organization statistics identify 150 million people with diabetes
      mellitus worldwide and suggest that this figure may double by 2025. In countries
      with a western lifestyle, the number of patients admitted for renal replacement
      therapy with diabetes as a co-morbid condition has increased significantly up to
      three to four times in a period of 10 years. Diabetes and renal failure are thus
      tightly linked diseases, and so is anemia. However, whether anemia may be
      worsened and/or directly, at least in part, caused by diabetes is not clearly
      elucidated yet. In this article, we review the prevalence, pathophysiology and
      consequences of anemia in diabetic patients.

PMID- 15452406
TI  - Hyaluronic acid in the treatment and prevention of skin diseases: molecular
      biological, pharmaceutical and clinical aspects.
AB  - The glycosaminoglycan hyaluronic acid (HA), or hyaluronan, is a major component
      of the extracellular matrix of skin, joints, eye and many other tissues and
      organs. In spite of its simple structure, HA demonstrates remarkable rheological,
      viscoelastic and hygroscopic properties which are relevant for dermal tissue
      function. Biological activities in skin, however, are also due to its interaction
      with various binding proteins (hyaladherins). Due to an influence on signaling
      pathways, HA is involved in the wound-healing process and scarless fetal healing.
      Increased HA concentrations have been associated with inflammatory skin diseases.
      In clinical trials, topical application of HA improved wound healing; in
      particular, acute radioepithelitis, venous leg ulcers or diabetic foot lesions
      responded to HA treatment. Moreover, as a topical drug delivery system for
      diclofenac, an HA gel has recently been approved for the treatment of actinic
      keratoses. Finally, chemical modifications led to new HA derivates and
      biomaterials, which may be introduced into therapy in the future. Therefore,
      ongoing research offers new horizons for the therapeutic use of this
      glycosaminoglycan which has been regarded as an inert structural component until
      recently.

PMID- 15452407
TI  - Penciclovir cream--improved topical treatment for herpes simplex infections.
AB  - Human herpesviruses can be found worldwide and cause many viral infections in
      immunocompetent as well as in immunocompromised patients. Herpes simplex virus
      (HSV) diseases can be the cause of life-threatening disease, especially in
      neonates. After initial infection, HSV persists latently in host neurons with the
      risk of periodical reactivation over a lifetime. The development of acyclovir, a
      potent and specific nucleoside inhibitor of the herpes DNA polymerase, was a
      milestone in the history of antiviral drugs in the late 1970s. During the last
      decades a better understanding of the replication and disease-causing state of
      HSV types 1 and 2 has been achieved enabling the development of new and potent
      antiviral compounds. In the mid-1990s, for example, valacyclovir and famciclovir
      were launched as prodrugs of acyclovir with improved bioavailability. Despite the
      numerous drugs available for the systemic treatment of HSV infections, the
      topical application of a cream containing an antiviral agent is still the most
      convenient method of treating herpes simplex labialis/facialis in the general
      population. For some time, the topical standard treatment for recurrent HSV
      infections has been acyclovir cream, despite the fact that the evidence for
      efficacy in recurrent episodes has been equivocal. Penciclovir, a novel acyclic
      nucleoside analogue, has demonstrated efficacy against HSV types 1 and 2 and
      seems to have a pharmacological advantage due to a prolonged half-life of its
      active form in HSV-infected cells. This review discusses and compares the topical
      treatment modalities available for HSV infections. As a conclusion, different
      studies are available that have shown that it is possible to reduce viral
      replication and hasten lesion resolution with 1% penciclovir treatment beyond the
      prodromal phase of the HSV infection. Comparing data of topical treatment with
      acyclovir and penciclovir revealed a superiority for penciclovir cream showing a
      significant decrease in time to lesion healing, lesion area and pain. While
      systemic acyclovir or valacyclovir may be valid drugs especially for HSV
      prophylaxis, 1% penciclovir cream should be preferred as topical treatment since
      there are good therapeutic results independent of the phase of development of
      herpetic eruptions.

PMID- 15452408
TI  - Integrated sun protection factor: a new sun protection factor based on free
      radicals generated by UV irradiation.
AB  - The present work uses the initial step of the whole cascade of biological effects
      in the skin, the creation of free radicals by means of UVA/UVB radiation, to
      develop a total sun protection factor. Until now, existing in vivo indices have
      not been fully satisfying: SPF only reflects protection from UVB light, and
      persistent pigment darkening is restricted to the UVA part of the sun spectrum.
      The quantitative measurement of free radicals generated in human skin biopsies by
      means of electron spin resonance X-band spectroscopy allows to determine a new
      total SPF. This new sun protection index covers all UVA/UVB wavelengths taking
      into account their effects in the epidermis as well as the dermis. Use of skin
      biopsies avoids exposure of human volunteers to potentially harmful radiations.
      The new index is always practically equal or lower than the in vivo SPF depending
      on the level of a product's UVA/UVB photoprotection balance. With this, we
      propose to name this new protection index 'integrated sun protection factor'.

PMID- 15452409
TI  - Ectoin: an effective natural substance to prevent UVA-induced premature
      photoaging.
AB  - With the help of a new 'UVA stress model', it was shown that Ectoin protects the
      skin from the effects of UVA-induced cell damage in a number of different ways.
      Using cell cultures, high-performance thin-layer chromatography, gel
      electrophoresis mobility shift assays, reverse transcriptase polymerase chain
      reaction, ion exchange chromatography and UV spectroscopy, it was demonstrated
      that the UVA-induced second messenger release, transcription factor AP-2
      activation, intercellular adhesion molecule-1 expression and mitochondrial DNA
      mutation could be prevented. The results obtained clearly demonstrate that Ectoin
      counteracts the effects of UVA-induced and accelerated skin aging at different
      cell levels.

PMID- 15452410
TI  - The combined effects of extracts containing carotenoids and vitamins E and C on
      growth and pigmentation of cultured human melanocytes.
AB  - In the present study, we investigated the effects of tomato extract (TE)
      containing lycopene and palm fruit extract (PE) rich in carotenoids on the growth
      and pigmentation of melanocyte cultures of Caucasian origin. The extracts were
      tested at different concentrations and in combination with vitamins E and C.
      Melanocytes with basic and increased (tyrosine-induced) pigmentation were treated
      in short-term and long-term experiments. Prevention of UVA-induced DNA damage was
      studied by using the comet assay. Melanocytes with stimulated melanin production
      showed reduced growth. Incubation of the cells with TE/PE (20/4 microg/ml) in
      combination with 35 microM vitamin E and 100 microM vitamin C (COMB 20/4) reduced
      this growth inhibition, especially in the long-term cultures. Increased
      production of melanin pigment was obtained when the cells were treated with 2.5 x
      and 10 x higher concentrations of the TE/PE and the same concentration of
      vitamins E and C (COMB 50/10 and 200/40). Reduced DNA damage was found after UVA
      irradiation in cells preincubated with COMB 50/10. The results indicate that the
      presence of carotenoids from TE and PE in combination with vitamins E and C may
      influence growth and pigmentation in melanocyte monocultures. Depending on the
      concentration of the carotenoid mixtures, their presence may provide some
      protection against the melanogenic intermediates and/or exogenous DNA damage.

PMID- 15452411
TI  - Dead but highly dynamic--the stratum corneum is divided into three hydration
      zones.
AB  - Topically applied water exerts mechanical stress on individual corneocytes as
      well as on the whole stratum corneum (SC), resulting in an alteration of barrier
      function. In this study we used complete skin biopsies and showed that the SC
      reacts to water stress as a highly optimized and well-regulated structure against
      osmotic changes. Following a relatively new cryo-processing protocol for cryo
      SEM, it is possible to reliably maintain and investigate the hydrated state of
      the SC and individual corneocytes after treatment with solutions of different
      ionic strength. Treatment with distilled water results in swelling of SC cells
      together with formation of massive water inclusions between adjacent cell layers.
      Treatment with 5-20% NaCl reveals three different hydration zones within the SC:
      Corneocytes near the live-dead transition zone can swell to nearly double their
      thickness. The second zone is the most compact, as the corneocytes here show the
      smallest thickness variation with all treatments. Within the outermost zone,
      again a massive swelling and loosening of intracellular filament packing can be
      observed. We therefore conclude that the SC itself is subdivided into three
      functional zones with individual water penetration and binding potentials. Since
      the second zone remains nearly unaffected by water stress, we propose that this
      zone hosts the functional SC barrier.

PMID- 15452412
TI  - Molecular analysis of the effect of topical imiquimod treatment of HPV 2/27/57
      induced common warts.
AB  - Imiquimod is effective in the treatment of genital warts and clinical studies
      suggest activity against common warts as well. We have analyzed the effect of
      topical imiquimod on gene expression and virus load in human papilloma virus
      (HPV) 2/27/57-induced common warts. mRNA was extracted from keratinocyte culture,
      from normal skin, from three untreated common warts and from three common warts
      treated topically with 5% imiquimod cream twice daily. Differential gene
      expression was demonstrated by RT-PCR and by cDNA microarray hybridization. We
      further analyzed viral DNA content in scales from three superficially pared
      imiquimod-treated warts by real-time PCR. Comparison of normal skin with wart
      tissue revealed that HPV 2/27/57 infection led to an induction of IL-6, IL-10 and
      interferon-gamma inducible protein (IP10) and to an up-regulation of TGF-beta. We
      could further detect expression of PCTAIRE-3, WNT2B, frizzled-3, notch-2, notch-4
      and BRCA2 in normal skin and common warts. Analysis of imiquimod-treated warts
      demonstrated that imiquimod enhanced IL-6 expression and induced IL-8, GM-CSF,
      MRP-8 and MRP-14. It could also be shown that imiquimod led to an infiltration of
      wart tissue with macrophages and to a strong decrease of viral copy number in
      warts within 3 months of treatment. Our data thus provide molecular proof of
      principle for imiquimod treatment of cutaneous common warts.

PMID- 15452413
TI  - Neuropsychological correlates of the PANSS Cognitive Factor.
AB  - OBJECTIVE: Factor analytic studies of the Positive and Negative Syndrome Scale
      (PANSS) have consistently isolated a factor that is frequently labeled as
      'cognitive'. The present study sought to further explore the factor by examining
      the relationships between 4 versions of the cognitive factor and a set of
      neuropsychological tests. METHOD: Thirty-seven inpatients diagnosed with
      schizophrenia or schizoaffective disorder were assessed with the PANSS and
      neuropsychological measures. RESULTS: Verbal intelligence and verbal memory were
      found to be most closely associated with cognitive factor scores. A global rating
      of illness severity showed greater relationships to cognitive variables than any
      cognitive factor. CONCLUSIONS: The PANSS cognitive factor may reflect verbal
      ability and memory, but is not sufficiently comprehensive to be considered as a
      replacement for direct assessment of cognitive functioning.

PMID- 15452414
TI  - Effects of 2,3-butanedione monoxime on induction of action potential bursts in
      central snail neurons: direct and indirect modulations of ionic currents.
AB  - The effects of 2,3-butanedione monoxime (BDM) on induction of action potential
      bursts were studied pharmacologically on the RP4 central neuron of giant African
      snail (Achatina fulica Ferussac). The effect of okadaic acid on the neuron was
      also tested. The RP4 neuron showed a spontaneous firing of action potential.
      Okadaic acid (1 micromol/l) did not alter the frequency of spontaneous action
      potential while BDM (3 mmol/l) reversibly elicited bursts of potential (BoP) of
      the RP4 neuron. The BoP elicited by BDM (3 mmol/l) were reversed 20 min after
      incubation with diazoxide (500 micromol/l) while the BoP were not altered in
      preparations treated with okadaic acid and BDM. The BDM-elicited BoP were not
      inhibited after administration with (a) hexamethonium (100 micromol/l), (b)
      atropine (1 mmol/l), (c) d-tubocurarine (100 micromol/l), (d) prazosin (100
      micromol/l), (e) propranolol (100 micromol/l), (f) calcium-free solution, (g)
      high K(+) (12 mmol/l) or (h) with high Mg(2+) (30 mmol/l) solutions. The BDM
      elicited BoP were inhibited by pretreatment with KT-5720 (10 micromol/l) or H89
      (10 micromol/l), the protein kinase A inhibitors. However, the BoP were not
      affected after application of chelerythrine (10 micromol/l) or Ro 31-8220 (10
      micromol/l), the protein kinase C inhibitors. Voltage-clamped studies revealed
      that BDM elicited a negative slope resistance (NSR) at membrane potentials
      between -50 and -10 mV. The NSR was not detectable at the same membrane potential
      in control RP4 neuron. It is suggested that the BoP elicited by BDM were not due
      to (1) the synaptic effects of neurotransmitters; (2) the activation of
      cholinergic, adrenergic receptors, or (3) phosphatase activity of the neuron. The
      BDM-elicited BoP were dependent on the protein kinase A related cAMP in the
      neuron and the delayed outward K(+) current may contribute to the BDM-elicited
      BoP.

PMID- 15452415
TI  - m-CPP, a 5-HT2C receptor agonist that modifies the perfusion pressure of the
      hindquarter vascular bed of anesthetized rat.
AB  - In the present work we studied the actions of the intra-arterial administration
      of meta-chlorophenylpiperazine (m-CPP - a 5-HT(2C) receptor agonist) in the
      hindquarters of the anesthetized rat. The lowest doses used (0.001, 0.01, 0.1,
      0.25 and 0.5 microg/kg) induced vasodilatation whereas the highest doses produced
      vasoconstriction (1, 6.25, 12.5 and 25 microg/kg). Both vasodilatation and
      vasoconstriction were inhibited by the 5-HT(1,2 )receptor antagonist
      methiothepin, whereas the 5-HT(2 )receptor antagonist ritanserin blocked only the
      vasoconstrictor responses. 1-[4-(1-Adamantanecarboxamido)butyl]-4-(2
      methoxyphenyl)piperazine (a 5-HT(1A) receptor antagonist) and ICI 118,551 (a
      beta(2)-receptor antagonist) failed to modify the vasodilator responses of m-CPP.
      Both BRL 15572 (a 5-HT(1D) receptor antagonist) and GR 55562 (a 5-HT(1B) receptor
      antagonist) only partially inhibited this action. Our data reveal that m-CPP
      induces the 5-HT(1 )and/or non-specific vasodilator effect and 5-HT(2)
      vasoconstrictor effects in the hindquarter vascular bed of the rat.

PMID- 15452430
TI  - Resolution and sensitivity of high field nuclear magnetic resonance spectroscopy.
AB  - The arrival of very high field magnets and cryogenic circuitries, and the
      development of relaxation-optimized pulse sequences have added powerful tools for
      increasing sensitivity and resolution in NMR studies of biomacromolecules. The
      potential of these advances is not fully realized in practice, however, since
      current experimental protocols do not permit sufficient data sampling for optimal
      resolution in the indirect dimensions. Here we analyze quantitatively how
      increasing resolution in indirect dimensions affects the S/N ratio and compare
      this with currently used sampling routines. Optimal resolution would require
      sampling up to approximately 3 R (2)(-1), and the S/N reaches a maximum at
      approximately 1.2 R (2)(-1). Currently used data acquisition protocols rarely
      sample beyond 0.4 R (2)(-1), and extending evolution times would result in
      prohibitively long experiments. We show that a general solution to this problem
      is to use non-uniform sampling, where only a small subset of data points in the
      indirect sampling space are measured, and possibly different numbers of
      transients are collected for different evolution times. Coupled with modern
      methods of spectrum analysis, this strategy delivers substantially improved
      resolution and/or reduced measuring times compared to uniform sampling, without
      compromising sensitivity. Higher resolution in the indirect dimensions will
      facilitate the use of automated assignment programs.

PMID- 15452431
TI  - Mars -- robust automatic backbone assignment of proteins.
AB  - MARS a program for robust automatic backbone assignment of (13)C/(15)N labeled
      proteins is presented. MARS does not require tight thresholds for establishing
      sequential connectivity or detailed adjustment of these thresholds and it can
      work with a wide variety of NMR experiments. Using only (13)C(alpha)/(13)C(beta)
      connectivity information, MARS allows automatic, error-free assignment of 96% of
      the 370-residue maltose-binding protein. MARS can successfully be used when data
      are missing for a substantial portion of residues or for proteins with very high
      chemical shift degeneracy such as partially or fully unfolded proteins. Other
      sources of information, such as residue specific information or known assignments
      from a homologues protein, can be included into the assignment process. MARS
      exports its result in SPARKY format. This allows visual validation and
      integration of automated and manual assignment.

PMID- 15452432
TI  - Backbone assignment of proteins with known structure using residual dipolar
      couplings.
AB  - A prerequisite for NMR studies of protein-ligand interactions or protein dynamics
      is the assignment of backbone resonances. Here we demonstrate that protein
      assignment can significantly be enhanced when experimental dipolar couplings
      (RDCs) are matched to values back-calculated from a known three-dimensional
      structure. In case of small proteins, the program MARS allows assignment of more
      than 90% of backbone resonances without the need for sequential connectivity
      information. For bigger proteins, we show that the combination of sequential
      connectivity information with RDC-matching enables more residues to be assigned
      reliably and backbone assignment to be more robust against missing data.
      Structural or dynamic deviations from the employed 3D coordinates do not lead to
      an increased error rate in RDC-supported assignment. RDC-enhanced assignment is
      particularly useful when chemical shifts and sequential connectivity only provide
      a few reliable assignments.

PMID- 15452433
TI  - A novel way of amino acid-specific assignment in (1)H-(15)N HSQC spectra with a
      wheat germ cell-free protein synthesis system.
AB  - For high-throughput protein structural analyses, it is indispensable to develop a
      reliable protein overexpression system. Although many protein overexpression
      systems, such as ones utilizing E. coli cells, have been developed, a lot of
      proteins functioning in solution still were synthesized as insoluble forms.
      Recently, a novel wheat germ cell-free protein synthesis system was developed,
      and many of such proteins were synthesized as soluble forms. This means that the
      applicability of this protein synthesis method to determination of the functional
      structures of soluble proteins. In our previous work, we synthesized (15)N
      labeled proteins with this wheat germ cell-free system, and confirmed this
      applicability on the basis of the strong similarity between the (1)H-(15)N HSQC
      spectra for native proteins and the corresponding ones for synthesized ones. In
      this study, we developed a convenient and reliable method for amino acid
      selective assignment in (1)H-(15)N HSQC spectra of proteins, using several
      inhibitors for transaminases and glutamine synthase in the process of protein
      synthesis. Amino acid selective assignment in (1)H-(15)N HSQC spectra is a
      powerful means to monitor the features of proteins, such as folding,
      intermolecular interactions and so on. This is also the first direct experimental
      evidence of the presence of active transaminases and glutamine synthase in wheat
      germ extracts.

PMID- 15452434
TI  - From NMR chemical shifts to amino acid types: investigation of the predictive
      power carried by nuclei.
AB  - An approach to automatic prediction of the amino acid type from NMR chemical
      shift values of its nuclei is presented here, in the frame of a model to
      calculate the probability of an amino acid type given the set of chemical shifts.
      The method relies on systematic use of all chemical shift values contained in the
      BioMagResBank (BMRB). Two programs were designed, one (BMRB stats) for extracting
      statistical chemical shift parameters from the BMRB and another one (RESCUE2) for
      computing the probabilities of each amino acid type, given a set of chemical
      shifts. The Bayesian prediction scheme presented here is compared to other
      methods already proposed: PROTYP RESCUE and PLATON and is found to be more
      sensitive and more specific. Using this scheme, we tested various sets of nuclei.
      The two nuclei carrying the most information are C(beta) and H(beta), in
      agreement with observations made in Grzesiek and Bax, 1993. Based on four nuclei:
      H(beta), C(beta), C(alpha) and C', it is possible to increase correct predictions
      to a rate of more than 75%. Taking into account the correlations between the
      nuclei chemical shifts has only a slight impact on the percentage of correct
      predictions: indeed, the largest correlation coefficients display similar
      features on all amino acids.

PMID- 15452435
TI  - Enhanced spectral resolution in RNA HCP spectra for measurement of (3)J(C2'P) and
      (3)J(C4'P) couplings and (31)P chemical shift changes upon weak alignment.
AB  - The 'out-and-back' 3D HCP experiment, using gradient- and sensitivity-enhanced
      detection, provides a convenient method for assignment of the (31)P NMR spectra
      and accurate measurement of the (31)P chemical shifts of ribonucleic acids. The
      (13)C resolution in such spectra can be doubled, at the cost of a 50% reduction
      in sensitivity, by combining (13)C evolution during the (13)C-[(31)P] de- and
      rephasing periods. The multiple connectivities observable for a given (31)P,
      including correlations to the intranucleotide C5'H(2) and C4'H groups, and the
      C2'H, C3'H and C4'H groups of the preceding nucleotide, permit independent
      measurements of the (31)P shift. The (13)C spectrum of these groups is typically
      crowded for an RNA molecule in isotropic solution and overlap becomes more
      problematic in media used to achieve partial alignment. However, many of these
      correlations are resolvable in the combined-evolution HCP spectrum. The
      difference in (31)P chemical shift between isotropic solution and a medium
      containing liquid crystalline Pf1 provides information on the orientation of
      phosphate groups. The intensities measured in the 3D HCP spectrum, obtained for
      an isotropic sample, yield values for the (3)J(C2'P) and (3)J(C4'P) couplings,
      thereby providing important restraints for the backbone torsion angles epsilon
      and beta. The experiments are illustrated for a uniformly (13)C-enriched, 24
      residue stem-loop RNA sequence, and results for the helical stem region show
      close agreement between observed Deltadelta((31)P) values and those predicted for
      a model A-form RNA helix when using a uniform (31)P CSA tensor. This confirms
      that Deltadelta((31)P) values can be used directly as restraints in refining
      nucleic acid structures.

PMID- 15452436
TI  - QSim, a program for NMR simulations.
AB  - We present QSim, a program for simulation of NMR experiments. Pulse sequences are
      implemented and analyzed in QSim using a mouse driven interface. QSim can handle
      almost any modern NMR experiment, using multiple channels, shaped pulses, mixing,
      decoupling, phase-cycling and pulsed field gradients. Any number of spins with
      any spin quantum number can, in theory, be used in simulations. Relaxation is
      accounted for during all steps of pulse sequences and relaxation interference
      effects are supported. Chemical kinetics between any numbers of states can be
      simulated. Both classical and quantum mechanical calculations can be performed.
      The result of a simulation can be presented either as magnetization as a function
      of time or as a processed spectrum.

PMID- 15452437
TI  - Characterisation of a mobile protein-binding epitope in the translocation domain
      of colicin E9.
AB  - The 61 kDa colicin E9 protein toxin enters the cytoplasm of susceptible cells by
      interacting with outer membrane and periplasmic helper proteins, and kills them
      by hydrolysing their DNA. The membrane translocation function is located in the N
      terminal domain of the colicin, with a key signal sequence being a pentapeptide
      region that governs the interaction with the helper protein TolB (the TolB box).
      Previous NMR studies (Collins et al., 2002 J. Mol. Biol. 318, 787-804) have shown
      that the N-terminal 83 residues of colicin E9, which includes the TolB box, is
      largely unstructured and highly flexible. In order to further define the
      properties of this region we have studied a fusion protein containing residues 1
      61 of colicin E9 connected to the N-terminus of the E9 DNase by an eight-residue
      linking sequence. 53 of the expected 58 backbone NH resonances for the first 61
      residues and all of the expected 7 backbone NH resonances of the linking sequence
      were assigned with 3D (1)H-(13)C-(15)N NMR experiments, and the backbone dynamics
      of these regions investigated through measurement of (1)H-(15)N relaxation
      properties. Reduced spectral density mapping, extended Lipari-Szabo modelling,
      and fitting backbone R(2) relaxation rates to a polymer dynamics model identifies
      three clusters of interacting residues, each containing a tryptophan. Each of
      these clusters is perturbed by TolB binding to the intact colicin, showing that
      the significant region for TolB binding extends beyond the recognized five amino
      acids of the TolB box and demonstrating that the binding epitope for TolB
      involves a considerable degree of order within an otherwise disordered and
      flexible domain. Abbreviations : Im9, the immunity protein for colicin E9; E9
      DNase, the endonuclease domain of colicin E9; HSQC, heteronuclear single quantum
      coherence; ppm, parts per million; DSS, 2,2-(dimethylsilyl)propanesulfonic acid;
      TSP, sodium 3-trimethylsilypropionate; T(1 - 61)-DNase fusion protein, residues 1
      61 of colicin E9 connected to the N-terminus of the E9 DNase by an eight residue
      thrombin cleavage sequence.

PMID- 15452438
TI  - 1H, (13)C and (15)N chemical shift assignments of the D2 domain of the fibroblast
      growth factor receptor.

PMID- 15452439
TI  - (1)H, (13)C and (15)N resonance assignments of the antifreeze protein cfAFP-501
      from spruce budworm at different temperatures.

PMID- 15452440
TI  - Assignment of (1)H, (13)C and (15)N resonances of the Escherichia coli YojN
      histidine-phosphotransferase (HPt) domain.

PMID- 15452441
TI  - (1)H, (13)C and (15)N NMR assignment of the homodimeric poplar phloem type II
      peroxiredoxin.

PMID- 15452442
TI  - (1)H, (13)C and (15)N assignments for the Archaeglobus fulgidis protein AF2095.

PMID- 15452443
TI  - Backbone (1)H, (13)C and (15)N resonance assignment of the N-terminal domain of
      human eRF1.

PMID- 15452444
TI  - (1)H, (15)N and (13)C backbone and side chain assignments of PSD-95 PDZ3 protein.

PMID- 15452445
TI  - TROSY-driven NMR backbone assignments of the 381-residue nucleotide-binding
      domain of the Thermus Thermophilus DnaK molecular chaperone.

PMID- 15452446
TI  - Breast self-examination: take all you can get out of it!

PMID- 15452447
TI  - Leptin and prostate: implications for cancer prevention--overview of genetics and
      molecular interactions.
AB  - Leptin's relation with obesity has been clearly demonstrated while its role in
      oncobiology is still largely unknown. Epidemiological studies on serum leptin
      provide valuable though controversial data, while in vitro studies consistently
      show leptin's angiogenic and proliferative potential in cancer. Leptin's activity
      is mediated by tissue-specific receptors, differentially expressed in organs such
      as the prostate. The molecular cascades triggered by leptin result in prostatic
      cell proliferation and angiogenic activity, thus linking the hormone mainly to
      prostate cancer prognosis. This review also addresses leptin's metabolic
      interactions with cytokines, growth factors or hormones, establishing perceptive
      pathways leading to carcinogenesis or prostate cancer progression and metastasis.
      Better understanding of these mechanisms may help in the development of new and
      more effective treatments for prostate cancer. The consolidation of leptin
      molecular genetics profile in prostate cancer patients may help to create
      susceptibility groups in normal individuals, facilitating a preventive dietary
      intervention or strategies for chemoprevention. We hypothesize that the balance
      between androgen and leptin levels may facilitate the increase in the ratio of
      androgen-independent prostate cancer cells to androgen-dependent cells in the
      tumour.

PMID- 15452448
TI  - Breast self-examination: longitudinal predictors of intention and subsequent
      behaviour.
AB  - This study analysed in a longitudinal design the relationship between past breast
      self-examination (BSE) behaviour, determinants, intention and future BSE
      behaviour in a population of adult Dutch women. Past behaviour and psychosocial
      determinants were assessed at T1, followed 6 weeks later (T2) with the assessment
      of the intention to perform BSE monthly. Half a year after the first measurement
      the current BSE behaviour was assessed by means of a telephone survey (T3) (total
      end response 78%, n=364). The questionnaires included BSE behaviour, intention,
      attitude (pros and cons of BSE, anticipated regret, moral obligation), social
      influence (support, modelling) and self-efficacy. Other background variables
      assessed were past BSE behaviour, and demographics. Although 81% of the women
      stated that they performed BSE, only 41% of the women performed BSE correctly.
      Women who performed BSE correctly differed from women who did not on all
      psychosocial determinants assessed a half year earlier, with the exception of
      anticipated regret. Stepwise multiple regression analyses showed that the
      psychosocial determinants explained 51% of the variance in intention to perform
      BSE, assessed 6 weeks later; past behaviour accounted for 2% of extra explained
      variance. Logistic regression analyses showed that past behaviour, the
      psychosocial determinants and intention were significant predictors of correct
      BSE behaviour a half year later (Nagelkerke's total explained variance was 47%).
      It was concluded that misperceptions of correct BSE behaviour was highly
      prevalent. Both the psychosocial determinants as well as past behaviour were
      important predictors of intention to perform BSE and subsequent BSE behaviour.

PMID- 15452449
TI  - Incidence, mortality and survival from prostate cancer in Cuba, 1977-1999.
AB  - Prostate cancer is currently one of the most common malignancies in Cuba, as
      worldwide. The present article analyses the burden of prostate cancer in Cuba.
      Cancer incidence, survival and mortality rates by province and age group were
      obtained from the National Cancer Registry and Mortality System from 1977 to
      1999. The incidence of prostate cancer has been rapidly increasing in the last 10
      years. In 1999 an incidence rate of 34.9 per 100,000 men was observed. Prostate
      cancer mortality is surpassed only by mortality due to lung cancer. An increase
      with successive diagnostic periods can be seen in all age groups. Geographical
      variations in the distribution of incidence and mortality rates in the country
      were also detected, with no major change in the diagnostic procedures. Our data
      suggest that the increased prostate cancer incidence represents a real increase
      in the number of patients with clinical disease.

PMID- 15452450
TI  - Practice of opportunistic prostate-specific antigen screening in Italy: data from
      the Health Search database.
AB  - The effectiveness of prostate-specific antigen (PSA) testing for opportunistic
      screening of prostate cancer is not yet well established, although this practice
      seems to be widely accepted. To estimate the opportunistic use of PSA by general
      practitioners (GPs) in Italy, we conducted a survey by querying the Health Search
      (HS) database, which collects clinical records from a representative sample of
      the Italian population. Clinical computerized data from 320 GPs and 221,557 male
      patients were analysed. Among total requests for PSA, 3% were linked to prostate
      cancer, 18% to a urological disease or symptom and 79% were not linked to any
      urological condition (opportunistic screening). Opportunistic screening was used
      for 31.4% of subjects over 50 with a significant (P<0.0001) difference between
      geographical areas (36.4% north, 33.5% central regions, 22.9% south and isles).
      This distribution was very similar to prostate cancer prevalence as it resulted
      from the HS data. PSA testing practice showed an increase over the years (12.7%
      of men over 50 in 2000, 14.3% in 2001 and 15.9% in 2002). In conclusion, the
      practice of opportunistic screening of prostate cancer seems to be extensively
      adopted by Italian GPs and is becoming more and more popular, although to date it
      is not supported by strong scientific evidence.

PMID- 15452451
TI  - Monitoring stage-specific trends in melanoma incidence across Europe reveals the
      need for more complete information on diagnostic characteristics.
AB  - Cutaneous malignant melanoma has been characterized by rapid and steady increases
      in incidence and mortality in white populations. Some reports mentioned declining
      trends in the mean thickness of these tumours, but other studies suggested a
      stable incidence of thick melanomas. The aim of this study was to describe the
      stage distribution of melanomas across Europe, with particular reference to
      temporal trends. Twenty-three cancer registries provided data sets containing
      information on stage and histology, 21 of which were used for a general
      description and nine for trends analyses. Despite a preponderance of missing
      data, interesting patterns emerged: a less favourable stage distribution in
      populations with relatively low incidence, but high case-fatality rates, and a
      favourable trend in stage and histology distribution over time, including a shift
      from later to earlier stages in recent years. Early detection campaigns raising
      awareness for thin lesions can potentially improve melanoma survival rates.
      Monitoring of stage-specific trends in melanoma incidence can assess the impact
      of such interventions. This paper demonstrates the potential utility of high
      quality, timely cancer registry data in pursuing such public health objectives
      and addresses the need for more complete information on diagnostic features of
      melanoma patients. This will allow more informative evaluations of preventive
      strategies.

PMID- 15452452
TI  - An integrated evaluation of socioeconomic and clinical factors in the survival
      from childhood acute lymphoblastic leukaemia: a study in Greece.
AB  - An evaluation of the role of socioeconomic factors in the survival of children
      with leukaemia, controlling for major clinical prognostic indicators, has been
      attempted in very few studies and the role of these factors may be different in
      various cultural settings. Our investigation aims to study the independent role
      of socioeconomic factors on the prognosis of childhood acute lymphoblastic
      leukaemia (ALL) in Greece. During a 7-year period (1996-2002) 293 cases of
      incident ALL were diagnosed and followed up in four Childhood Haematology
      Oncology Units, which covered over half of all childhood ALL cases nationwide. At
      the time of diagnosis, information concerning age, gender, maternal schooling,
      maternal marital status, sibship size, distance of residence from the treating
      centre, attendance of day care centre and clinical information was recorded. The
      influence of these factors on survival was studied by modelling the data through
      Cox's proportional-hazards regression. After adjustment for clinical prognostic
      factors, children of mothers who were not currently married, were of low
      educational level or were living far from the treating centre tended to have
      lower survival (P-values 0.02, 0.14 and 0.08, respectively). There was also
      evidence that two factors that are predictive of disease occurrence, that is
      sibship size and attendance of day care centre, may also predict survival (P
      values 0.04 and 0.26, respectively). In conclusion, socioeconomic factors are
      likely to influence survival from ALL at least in some sociocultural contexts.
      Moreover, there is evidence that factors that could affect incidence of ALL
      through modulation of herd immunity may also have prognostic implications for
      this disease.

PMID- 15452453
TI  - Clinical and biochemical features of sporadic and hereditary phaeochromocytomas:
      an analysis of 41 cases investigated in a single endocrine centre.
AB  - The aims of this study were to estimate the prevalence of phaeochromocytomas
      among adrenal tumours and to analyse the clinical and biochemical features of
      sporadic and hereditary tumours. Our series of 609 adrenal tumours evaluated
      between January 1995 and July 2003 was reviewed. Catecholamine content in
      phaeochromocytoma tissues was also determined and correlated with clinical
      behaviour and biochemical parameters of patients. Forty-one (6.7%) of the 609
      patients had phaeochromocytomas, of which 28 were sporadic (25 benign and three
      malignant) and 13 (all benign) were associated with hereditary diseases (multiple
      endocrine neoplasia type 2A in seven cases from four unrelated families carrying
      mutations of the RET gene, von Hippel-Lindau disease in two unrelated cases with
      mutations of the VHL gene, and type 1 neurofibromatosis in four unrelated cases).
      Bilateral tumours were found in three patients with hereditary syndromes and in
      one sporadic case. Tumour diameter was slightly but not significantly greater in
      patients with hereditary than in those with sporadic tumours. Systolic but not
      diastolic blood pressure was significantly higher in patients with sporadic
      compared with those with hereditary tumours, but comparison of other clinical
      data and biochemical parameters indicated an absence of significant differences
      in the mean age, presenting symptoms, heart rate, or fasting serum glucose
      levels. Tissue catecholamine content measured in 8 sporadic and 5 hereditary
      phaeochromocytomas was highly variable and it failed to show significant
      differences between hereditary and sporadic tumours. These results indicate a
      high proportion of hereditary diseases among patients with phaeochromocytomas.
      Genetic and clinical testing for hereditary diseases may be of great help to
      offer an appropriate treatment, follow-up and family screening for these
      patients.

PMID- 15452454
TI  - Inhibition of DMBA/croton oil-induced two-stage mouse skin carcinogenesis by
      diphenylmethyl selenocyanate.
AB  - Selenium, an essential micronutrient, is associated with antioxidant functions,
      physiological defence mechanisms against different diseases including several
      types of cancers. Search for new selenium compounds with more chemopreventive
      activities and lesser toxicities are in progress. In the present study, the
      antioxidative roles of a synthetic organoselenium compound, diphenylmethyl
      selenocyanate, were evaluated against 7,12-dimethylbenz(a)anthracene
      (DMBA)/croton oil-induced two-stage mouse skin carcinogenesis model. The compound
      was administered orally in carcinogen-induced mice in two different non-toxic
      doses: 2 mg/kg body weight and 3 mg/kg body weight. Significant inhibition in the
      incidence of papilloma formation (58-80%) as well as in the cumulative number of
      papilloma per papilloma-bearing mouse were observed in the treated groups as
      compared with the carcinogen control group. The compound was also found to
      significantly upregulate different phase II detoxifying enzymes in liver cytosol
      such as glutathione-S-transferase (P<0.01), catalase (P<0.01) and superoxide
      dismutase (SOD) (P<0.01) when measured after 15 days and also after 12 weeks of
      first DMBA treatment. Lipid peroxidation measured as the thiobarbituric acid
      reactive substances in liver microsomes was significantly inhibited (P<0.05) in a
      dose-dependent manner by diphenylmethyl selenocyanate. Thus the compound exerts
      its chemopreventive activity by reducing papilloma formation during chemically
      induced carcinogenesis, which in turn, may be through modulating the level of
      lipid peroxidation and phase II detoxifying enzyme system at the doses evaluated.

PMID- 15452455
TI  - Suppressive effects of nitric oxide production and inducible nitric oxide
      synthase (iNOS) gene expression by Calystegia soldanella methanol extract on
      lipopolysaccharide-activated RAW 264.7 cells.
AB  - Since nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS) has
      been found to be involved in various pathophysiological processes, including
      inflammation and carcinogenesis, the modulators of NO synthesis or expression
      have been considered as potential anti-inflammatory and cancer chemopreventive
      agents. In this study, to procure the iNOS inhibitors from natural products, we
      evaluated 57 methanol extracts of natural products including Korean indigenous
      plants for the inhibition of NO formation on lipopolysaccharide (LPS)-activated
      mouse macrophage-like RAW 264.7 cells. As a result, several extracts including
      those from Actinodaphne lancifolia, Calystegia soldanella, Caryratia japonica,
      Citrus dachibana, Dystaenia takeshimana, Erysimum aurantiacum, Hovenia undulata,
      Stewartia koreana and Viburnum awabuki showed potent inhibitory activities of NO
      production (>70% inhibition at the test concentration of 40 microg/ml). In
      particular, the extract of Calystegia soldanella showed a potential inhibition of
      NO production in a dose-dependent manner (IC50=4.3 microg/ml). Subsequent study
      also exhibited that the extract of Calystegia soldanella significantly suppressed
      iNOS protein and gene expression in a dose-dependent manner. These results
      suggest that Calystegia soldanella might be a new potential candidate for
      developing an iNOS inhibitor from natural products and also could be warranted
      for further elucidation of active principles for the development of new anti
      inflammatory and/or cancer chemopreventive agents.

PMID- 15452456
TI  - Biomarkers in non-small cell lung cancer prevention.
AB  - Identification of biomarkers is one of the most promising approaches for the
      detection of early malignant or even premalignant lesions with the chance of
      diagnosing early stages of non-small cell lung cancer that could be treated
      curatively. Alterations of chromosomes (3p, 5q, 9p), genes (Rb, C-myc, C-mos,
      hTERT), proteins (p16, p53, K-ras, hnRNP A2/B1, MCM2, EGFR, erbB-2, erbB-3, erbB
      4) and others can be found in lung cancer. Some of these occur at early stages of
      the disease and few could serve as potential screening markers. The actual
      literature is reviewed and the relevance of the different biomarkers for early
      lung cancer detection is discussed.

PMID- 15452457
TI  - On the technicalities of discovering and applying protein biomarkers for cancer
      prevention.
AB  - Primary prevention of cancer is one of the key approaches used to combat cancer.
      By identifying people at high risk of developing cancer, it becomes possible to
      develop intervention efforts on prevention rather than treatment. Prevention
      includes avoiding exposure to known cancer-causing agents, enhancement of host
      defence mechanisms, modifying lifestyle and chemoprevention. The latter is the
      use of specific agents to suppress or reverse carcinogenesis and thereby prevent
      the development of cancers. Understanding primary molecular events in tumour
      development is therefore the key. The causes of cancer first produce reversible
      changes in the target cells, and a long interval is expected between cancer
      induction and the presentation of disease. Up to now, we had no reliable
      biomarkers to monitor these primary events, to select high-risk groups and
      individuals likely to get cancer, and to monitor preventive treatments or
      strategies to normalize these markers and prevent the individual from getting
      cancer. Recent developments in proteomic research, however, promise to deliver on
      these major needs. We here describe the technological armatorium of, and the
      recent advances in the field of protein biomarker discovery and discuss the
      future use of protein biomarkers for (1) reliable identification of high-risk
      groups; (2) clinical guidance of preventive strategies; and (3) elucidation of
      the mechanism of action for novel (natural product) prevention therapies and
      regimens.

PMID- 15452458
TI  - Mediterranean diet and cancer risk.
AB  - Various aspects of the Mediterranean diet are considered favourable with regard
      to cancer risk. These aspects were analysed using data from a series of case
      control studies conducted in northern Italy between 1983 and 2001 on over 12,000
      cases of 20 cancer sites and 10,000 controls. For most epithelial cancers, the
      risk decreased with increasing vegetable and fruit consumption, with odds ratios
      (OR) between 0.3 and 0.7 for the highest versus the lowest tertile. Subjects
      reporting frequent red meat intake showed ORs above unity for several common
      neoplasms. Conversely, fish (and consequently, n-3 fatty acids) tended to be
      another favourable dietary indicator. Wholegrain food intake was related to
      reduced risk of several types of cancer, particularly of the upper digestive
      tract, probably on account of its high fibre content. Fibres were in fact found
      to be protective with regard to colorectal and other selected cancers. In
      contrast to wholegrain, refined grain intake, and consequently glycaemic load,
      was associated with an increased risk of different types of cancer, including
      those of the upper digestive tract, colorectum, breast and endometrium. These
      results thus suggest that a low-risk diet for cancer entails increasing
      vegetables and fruit, reducing meat, but also refined carbohydrate consumption.
      Furthermore, olive oil and other unsaturated fats, which may be a unique common
      characteristic of the Mediterranean diet, should be preferred to animal and
      saturated fats. A score summarizing the major characteristics of the
      Mediterranean diet was inversely and consistently related to the risk of selected
      cancer sites. Regular consumption of pizza, one of the most typical Italian
      foods, showed a reduced risk of digestive tract cancers. Pizza could however
      simply be an indicator of a typical Italian diet.

PMID- 15452459
TI  - Mediterranean diet and longevity.
AB  - While several investigations have focused on the association between individual
      foods and nutrients upon the development of chronic diseases, few have examined
      the role that entire dietary patterns may play in health and disease. A dietary
      pattern generally considered to have beneficial health effects is that of the
      Mediterranean diet. In this paper, five cohort studies exploring the association
      of Mediterranean diet with overall mortality and hence longevity are reviewed. A
      number of conclusions can be drawn. First, there appears to exist sufficient
      evidence that diet does indeed influence longevity. Secondly, an optimal diet for
      the prevention of both coronary heart disease and cancer is likely to extensively
      overlap with the traditional Mediterranean diet. It is not yet clear which
      components in the Mediterranean diet are more important for its apparent health
      effects, but olive oil, plant foods and moderate wine consumption are likely
      candidates.

PMID- 15452460
TI  - Report of the International Digestive Disease Alliance, New Orleans 2004--in
      collaboration with the OMED Colorectal Cancer Screening Committee.

PMID- 15452461
TI  - Report of the OMED Colorectal Cancer Screening Committee Meeting, New Orleans,
      2004--in collaboration with the IDCA.

PMID- 15452463
TI  - Generic levothyroxine.

PMID- 15452464
TI  - Gemifloxacin (factive).

PMID- 15452465
TI  - Cinacalcet (sensipar).

PMID- 15452466
TI  - Two-dimensional strain-a novel software for real-time quantitative
      echocardiographic assessment of myocardial function.
AB  - OBJECTIVES: We sought to assess the feasibility of 2-dimensional strain, a novel
      software for real-time quantitative echocardiographic assessment of myocardial
      function. METHODS: Conventional and a novel non-Doppler-based echocardiography
      technique for advanced wall-motion analysis were performed in 20 patients with
      myocardial infarction and 10 healthy volunteers from the apical views. Two
      dimensional strain is on the basis of the estimation that a discrete set of
      tissue velocities are present per each of many small elements on the ultrasound
      image. This software permits real-time assessment of myocardial velocities,
      strain, and strain rate. These parameters were also compared with Doppler tissue
      imaging measurements in 10 additional patients. RESULTS: In all, 80.3% of infarct
      and 97.8% of normal segments could be adequately tracked by the software. Peak
      systolic strain, strain rate, and peak systolic myocardial velocities, calculated
      from the software, were significantly higher in the normal than in the infarct
      segments. In the 10 additional patients, velocities, strain, and strain rate
      obtained with the novel software were not significantly different from those
      obtained with Doppler tissue imaging. CONCLUSION: Two-dimensional strain can
      accomplish real-time wall-motion analysis, and has the potential to become a
      standard for real-time automatic echocardiographic assessment of cardiac
      function.

PMID- 15452467
TI  - Myocardial contrast echocardiography predicts left ventricular remodelling after
      acute myocardial infarction.
AB  - BACKGROUND: We investigated whether the extent of residual myocardial viability
      demonstrated by myocardial contrast echocardiography (MCE) predicts the degree of
      left ventricular (LV) remodelling after acute myocardial infarction as assessed
      by cardiovascular magnetic resonance. METHODS: Accordingly, 25 patients underwent
      MCE 5 to 7 days after acute myocardial infarction followed by cardiovascular
      magnetic resonance assessment of LV end-diastolic volume, LV end-systolic volume,
      and LV ejection fraction. A contrast perfusion index was calculated within the
      infarct-related territory. RESULTS: LV end-diastolic and end-systolic volumes
      were significantly smaller (138 +/- 38 vs 188 +/- 43 mL, P =.008, and 86 +/- 35
      vs 119 +/- 49 mL, P =.01, respectively) and LV ejection fraction was
      significantly higher (52 +/- 5.4 vs 31.5 +/- 3.2%, P> =.02) in patients showing
      good myocardial viability (contrast perfusion index </= 1.5) compared with those
      without viability. MCE was the only multivariate predictor of LV volumes and LV
      ejection fraction at 2 weeks and 6 months. CONCLUSIONS: The extent of residual
      myocardial viability as demonstrated by MCE predicts the degree of LV remodelling
      after acute myocardial infarction.

PMID- 15452468
TI  - Early impairment of myocardial blood flow reserve in men with essential
      hypertension: a quantitative myocardial contrast echocardiography study.
AB  - OBJECTIVE: Aims of this study were to: (1) demonstrate whether quantitative
      myocardial contrast echocardiography could detect an index of myocardial blood
      flow reserve through the analysis of refilling curves generated by microbubble
      transit into myocardium both at rest and after vasodilatation induced by
      dipyridamole; and (2) explore with this method myocardial microcirculatory
      function in two different models (ie, patients with essential hypertension and
      control subjects). METHODS: Two groups of strictly age-matched men were studied
      (case-control study): 12 patients who were adults (28.2 +/- 0.2 years) and
      asymptomatic with never-treated essential hypertension, a mild degree of left
      ventricular hypertrophy, and normal left ventricular function; and 12 control
      subjects. Quantitative myocardial contrast echocardiography was performed in all
      study participants. We used second-generation ultrasound microbubbles as
      echocardiography contrast agent. Real-time color-coded power modulation was
      performed with a phased-array system interfaced to a S3 transducer (1.3-3.6 MHz).
      RESULTS: In control subjects there was little increase in myocardial blood volume
      (30%) between basal and hyperemic status (P <.05); in patients with hypertension
      this parameter increased by 22% (P <.05). Myocardial blood velocity increased
      after dipyridamole by 270% in control subjects (P <.01), whereas for patients
      with hypertension this parameter increased only by 150% (P <.02). The index of
      myocardial blood flow reserve was significantly lower for patients with
      hypertension than in control subjects (3.3 +/- 0.3 vs 4.4 +/- 0.3, respectively;
      P <.01). CONCLUSION: Results of our study documented that myocardial
      microcirculation in young adult patients with hypertension showed an early
      impairment in the vasodilatation capacity of the resistance arterioles under
      dipyridamole-induced hyperemia, as demonstrated by a reduction of myocardial
      blood flow reserve. Myocardial blood velocity increased after dipyridamole
      induction in control subjects, whereas patients with hypertension showed a
      significantly lesser increase. Myocardial blood flow reserve was significantly
      lower for patients with hypertension because of an early impairment in
      vasodilatation capacity of resistance arterioles under dipyridamole-induced
      hyperemia.

PMID- 15452469
TI  - Comparison of peak and postexercise treadmill echocardiography with the use of
      continuous harmonic imaging acquisition.
AB  - OBJECTIVES: We sought to compare the feasibility and accuracy of peak and
      postexercise treadmill echocardiography with the use of continuous harmonic
      imaging capture. BACKGROUND: Previous work has demonstrated the superiority of
      peak exercise echocardiography (EE) as compared with post-EE for the diagnosis of
      coronary artery disease (CAD). However, most of these studies used fundamental
      imaging and view-per-view acquisition systems. Technical advantages in stress
      echocardiography include harmonic imaging and continuous imaging capture.
      METHODS: The study group included 650 patients (423 men; 60 +/- 12 years) who
      were submitted to peak and postexercise treadmill echocardiography. RESULTS:
      Postexercise images were acquired within 55 seconds after exercise (28 +/- 10).
      The number of segments visualized in each view were similar at peak and post-EE
      except for the parasternal short-axis view, which was better qualified at
      postexercise. For analysis of diagnostic capability we included 312 patients: 195
      were included on the basis of having had an EE and a coronary angiography,
      whereas 117 patients with pretest probability of CAD < 10% who had atypical chest
      pain or were asymptomatic were also included and considered as having no CAD. CAD
      (>/=50% stenosis) was confirmed in 159 patients. Positive EE was defined as
      ischemia or necrosis. Sensitivity for CAD was higher with peak imaging (92% vs
      77%, P <.001), with similar specificity (78% vs 87%, P = not significant) and
      accuracy (85% vs 82%, P = not significant). CONCLUSION: Peak treadmill EE is
      technically feasible and has higher sensitivity for CAD than posttreadmill EE.
      Therefore, in the clinical setting, peak EE should be performed for diagnostic
      purposes.

PMID- 15452470
TI  - Comparison of image quality between a narrow caliber transesophageal
      echocardiographic probe and the standard size probe during intraoperative
      evaluation.
AB  - BACKGROUND: Transesophageal echocardiography (TEE) has become an integral part of
      the evaluation and monitoring of patients during cardiac operation. Until
      recently, the smallest TEE probe with multiplane imaging measured 13 mm in
      diameter. This size is now standard for adult TEE probes. Recently, a new TEE
      probe has become available (MiniMulti TEE probe, Philips Medical Systems,
      Andover, Mass), which has a diameter of 8 mm. Although using a smaller probe is
      attractive, the quality of images it generates when used in adults has not yet
      been examined. OBJECTIVE: The purpose of this study was to compare TEE studies
      done with both probes. METHODS: After informed consent was obtained, full
      intraoperative TEE studies were performed in 20 patients with a small pediatric
      probe. The study was then repeated using a standard adult probe. The studies were
      read in random order by two experienced echocardiographers blinded to probe used.
      For each study, 18 anatomic cardiac structures and 5 Doppler patterns were
      subjectively graded as excellent (1), good (2), fair (3), or poor (4) in quality.
      The average score for each structure or Doppler profile was computed for each
      probe. RESULTS: The average score for all findings was lower (better) for the
      adult TEE probe (1.4 +/- 0.4 vs 1.7 +/- 0.4; P =.003). When each finding was
      compared separately, several cardiac structures (left ventricle [LV],
      pericardium, right ventricle [RV], interatrial septum, left atrium, left atrial
      appendage, mitral valve, aortic valve) had better scores with the adult probe,
      and the differences for the LV and RV were larger than those for the other
      findings (LV scores differed by 0.7, P =.0004; RV scores differed by 0.5, P
      =.01). There was no significant difference between probes when evaluating venous
      structures (coronary sinus, superior vena cava, pulmonary vein), the thoracic
      aorta, or the right atrium or tricuspid valve. In addition, Doppler patterns were
      not significantly different with the two probes. There were two findings that
      were missed with the small probe and seen with the adult probe (one aortic plaque
      and one left atrial appendage thrombus). CONCLUSIONS: In the adult, the larger
      probe provides better images, particularly of the RV and LV. In addition,
      important findings may be missed with the smaller probe. However, if the adult
      probe cannot be passed, the pediatric probe is a reasonable alternative.

PMID- 15452471
TI  - A different method for measuring mitral valve area with special emphasis on
      concomitant aortic regurgitation: A new application of proximal isovelocity
      surface area method.
AB  - Measurement of mitral valve area is still a challenge for the echocardiographers.
      Each method has its own limitations. In this study we assessed a different method
      and compared it with the other methods. The study included 50 consecutive
      patients with mitral stenosis. The reference method was planimetry. The suggested
      method was compared with the pressure half-time method, proximal isovelocity
      surface area method with and without angular correction, and the continuity
      method. There was a good correlation between each method and planimetry. The
      suggested method had the best correlation both for patients with and without
      aortic regurgitation. The pressure half-time method and continuity method
      overestimated the mitral valve area for patients with aortic regurgitation,
      whereas proximal isovelocity surface area method without angular correction
      overestimated the area in all patients. In conclusion, this method has very good
      correlation with planimetry. It can be used both in patients with and without
      aortic regurgitation.

PMID- 15452472
TI  - Agitated saline versus polygelatine for the echocardiographic assessment of
      patent foramen ovale.
AB  - BACKGROUND: The choice of the optimal echo contrast agent could be of relevance
      for the detection of a patent foramen ovale (PFO). This study compares agitated
      saline solution and oxypolygelatine (OXY) with respect to their ability to detect
      a PFO. METHODS: A total of 34 patients (13 women, age 45 +/- 16 years) underwent
      both transthoracic and transesophageal echocardiography. The appearance of
      contrast and the presence of a PFO was assessed visually and by acoustic
      densitometry for both agents. RESULTS: The sensitivity of the detection of a PFO
      (22 patent, 65%) was 71% with saline versus 84.6% for OXY. Maximum, mean acoustic
      densitometry grayscale intensity values and the duration of opacification was
      significantly higher for OXY versus saline for all chambers. CONCLUSIONS: OXY has
      superior echo properties that translate into a higher sensitivity for the
      detection of a PFO. The choice of the optimal agent must be considered for
      clinical routine and research studies.

PMID- 15452473
TI  - Regional functional depression immediately after ventricular septal defect
      closure.
AB  - Left ventricular ejection is depressed immediately after repair of ventricular
      septal defect (VSD). Postrepair functional depression seen after VSD closure
      could result from a reduction in preload. However, other mechanisms could be at
      work. Functional depression could also be caused by closure of a low-impedance
      path for left ventricular ejection, the introduction of a stiff akinetic patch,
      or the operation itself. We reasoned that functional depression mediated by
      changes in preload or afterload should symmetrically affect end-diastole and end
      systole, whereas depression resulting from changes in septal mechanics should be
      localized. We, therefore, performed segmental wall-motion analysis on
      intraoperative echocardiograms from patients undergoing VSD and atrial septal
      defect repair. After VSD closure, there was an asymmetric change in left
      ventricular end-systolic segment length and a decrease in fractional segment
      shortening localized to the septal and lateral walls, whereas patients with
      atrial septal defect had a symmetric increase in fractional shortening. These
      results suggest that acute functional depression after VSD repair is a result of
      localized impairment of septal function.

PMID- 15452474
TI  - Echocardiographic features of atrial myocarditis with giant cells: a case report.
AB  - We report a case of restrictive cardiomyopathy in which a distinct endothelial
      thickening of the atrial wall and pulmonary vein orifices was noted on
      transesophageal echocardiography. Echocardiographically guided endomyocardial
      biopsy of the thickening revealed an inflammatory infiltrate that was rich in
      giant cells and provided important clues about an underlying immune mechanism for
      the pathogenesis. Positive results from the antineutrophil cytoplasmic
      autoantibody assay supported the diagnosis of Wegener's granulomatosis. After
      immunosuppressive therapy, the endomyocardial thickening completely resolved, but
      the restrictive cardiomyopathy did not reverse.

PMID- 15452475
TI  - Electric dissociation within left atrial appendage diagnosed by Doppler
      echocardiography.
AB  - We describe a patient who presented with a transient ischemic event in whom
      transesophageal echocardiography showed presence of an accessory lobe within the
      left atrial appendage that was in atrial fibrillation by pulsed wave Doppler when
      the left and right atrial appendages, pulmonary vein, and right atria were in
      sinus rhythm.

PMID- 15452476
TI  - Left ventricular intracardiac metastatic germ cell tumor presenting with
      hemorrhagic cerebrovascular event.
AB  - We describe an unusual case of a 26-year-old man admitted with respiratory
      distress and found to have testicular cancer metastatic to the lung and heart.
      Twelve days after admission, the patient experienced multiple hemorrhagic
      strokes. Echocardiography demonstrated testicular cancer metastatic to the septal
      surface of the left ventricle of the heart with presumed embolization to the
      cerebrovascular region. The patient received chemotherapy and radiation therapy
      to the areas of tumor mass with subsequent resolution of tumor burden. This is
      the first reported case of metastasis from embryonal carcinoma of the testis to
      the left ventricle of the heart.

PMID- 15452477
TI  - Total anomalous pulmonary venous return involving drainage above, below, and to
      the heart: a mixed bag.

PMID- 15452478
TI  - American Society of Echocardiography recommendations for use of echocardiography
      in clinical trials.

PMID- 15452479
TI  - Trabeculation and left ventricular hypertrabeculation/noncompaction.

PMID- 15452480
TI  - Pain management: a growing awareness of the issue.

PMID- 15452481
TI  - Elephants in the corner.

PMID- 15452482
TI  - Alcohol screening tool.

PMID- 15452483
TI  - Rapid sequence intubation kit.

PMID- 15452484
TI  - Challenge to CEN radioactive contamination review question.

PMID- 15452486
TI  - Once upon a time: ED staffing should reflect complex, comprehensive care and not
      just the census.

PMID- 15452519
TI  - A 60-year-old man with pneumothorax and subcutaneous air after vomiting.

PMID- 15452520
TI  - Reducing pain in ED patients during lumbar puncture: the efficacy and feasibility
      of iontophoresis, collaborative approach.
AB  - INTRODUCTION: This study examined the efficacy and feasibility of a collaborative
      iontophoresis procedure for dermal anesthesia prior to lumbar puncture (LP) in
      adult ED patients. METHODS: Patients were randomized to receive lidocaine by
      iontophoresis or needle infiltration. Emergency nurses and physicians completed a
      collaborative LP procedure in those randomized to iontophoresis. Usual care was
      provided for needle infiltration subjects. Pain was assessed at 3 points using an
      11-point numeric rating scale to measure pain, and provider satisfaction was
      recorded. RESULTS: Ninety subjects completed the protocol: infiltration group (n
      = 48) and iontophoresis group (n = 42). Subjects in the lidocaine infiltration
      group reported significantly more pain (mean, 4.1A+/-2.6) than subjects in the
      iontophoresis group (mean, 0.9A+/-1.6) ( t82 = 1.26, P =.000). There was no
      significant difference between the pain experienced during the lumbar puncture by
      both groups. Mean pain score during LP was 3.7 (+/-2.7) for iontophoresis
      compared to 3.4 (+/-2.9) for infiltration. More iontophoresis subjects (18 or
      43.9%) required "rescue" lidocaine than infiltration subjects (12 or 24.5%) (chi
      square 1 =3.79, P =.0515). Providers reported greater satisfaction with the
      collaborative procedure compared to physician administered lidocaine infiltration
      and anecdotally reported that iontophoretic anesthesia administration does not
      obscure anatomical landmarks, as needle infiltration can. Time for completion of
      dermal anesthesia using the iontophoretic procedure was longer than time for
      completion of dermal anesthesia using the lidocaine infiltration procedure (12A+/
      12 min vs 2A+/-1.7 min); however, no statistically significant difference in
      total LP time or ED length of stay was found. NURSING IMPLICATIONS: Dermal
      anesthesia by lidocaine iontophoresis in patients undergoing an LP with emergency
      nurses and physicians working in collaboration during the procedure takes longer,
      but decreases the pain of administering anesthesia, increases provider
      satisfaction, and fosters collaborative practice in the emergency setting.
      Iontophoretic administration of anesthesia for LP is now an option for dermal
      anesthesia in our emergency department.

PMID- 15452521
TI  - Implementation of an ED protocol for pain management at triage at a busy Level I
      trauma center.

PMID- 15452522
TI  - A shift from demerol (meperidine) to dilaudid (hydromorphone) improves pain
      control and decreases admissions for patients in sickle cell crisis.

PMID- 15452523
TI  - Clinical policy: evidence-based approach to pharmacologic agents used in
      pediatric sedation and analgesia in the emergency department.

PMID- 15452524
TI  - Knowledge assessment and preparation for the Certified Emergency Nurses
      Examination.

PMID- 15452525
TI  - The Rhode Island nightclub fire: the story from the perspective of an on-duty ED
      nurse.

PMID- 15452526
TI  - Made a med error? Tell everyone!

PMID- 15452527
TI  - Tips for managing pain more effectively.

PMID- 15452528
TI  - Total airway obstruction by a mucous plug relieved with extreme positive
      pressure: case report of a pediatric patient.

PMID- 15452530
TI  - An informal discussion of emergency nurses' current clinical practice: what's new
      and what works.

PMID- 15452531
TI  - Avoiding disastrous outcomes with rapid intravenous push medications.

PMID- 15452532
TI  - Pediatric spinal immobilization: C-spines, car seats, and color-coded collars.

PMID- 15452538
TI  - Preparing ED staff for a JCAHO survey: innovative strategies to update staff.

PMID- 15452539
TI  - Severe headache in a 62-year-old woman seen at an immediate care center.

PMID- 15452540
TI  - A 17-year-old girl with severe groin pain and an inability to ambulate during a
      gymnastics competition.

PMID- 15452541
TI  - New drugs of abuse update: Foxy Methoxy.

PMID- 15452542
TI  - Motor vehicle crashes among the elderly: advocates cite the need for mandatory
      retesting of elderly drivers.

PMID- 15452543
TI  - The pupil examination in the trauma patient.

PMID- 15452544
TI  - Exercises in critical thinking at triage: prioritizing patients with similar
      acuities.

PMID- 15452545
TI  - ProjectHelping Hands: medical mission organization increases educational focus
      with village health care provider seminar in Caranavi, Bolivia.

PMID- 15452546
TI  - Antibodies to CD20 and MHC class II antigen bound to B-lymphoma cells accumulate
      in shed cytoplasmic fragments.
AB  - Antibodies (Abs) to CD20 and MHC class II antigen were found to exhibit a novel
      processing pathway after binding to the surface of RL B-lymphoma cells. The Abs
      were 'excreted' as a part of large cytoplasmic fragments. These fragments formed
      at cell-cell junctions, but gentle dispersal of the cells, to form a single-cell
      suspension of high viability, caused the release of most of the fragments. This
      process also occurred in Raji cells and in three other B-lymphoma cell lines (of
      seven tested). Six B-lymphoblastoid cell lines tested did not form these objects.
      Once they were recognised, the fragments could be identified in cell preparations
      by phase contrast microscopy or after staining with Wright's stain. They were
      induced by the binding of certain Abs, but not by most Abs bound to the cell
      surface. The mode of formation, detailed morphology and function of these
      cytoplasmic fragments remain to be determined. They are similar in many respects
      to the lymphoglandular bodies that have been described by pathologists for many
      years, which are characteristic of B-cell lymphoma, but which have not previously
      been described in cell lines. This type of Ab processing, if it occurs in
      patients, will have an impact on the therapeutic use of these Abs.

PMID- 15452547
TI  - Pyridoxal phosphatase is a novel cancer autoantigen in the central nervous
      system.
AB  - Autoantibodies against many proteins are common in sera from patients with
      various types of cancer. These antibodies are sometimes involved in the
      development of conditions associated with cancer, such as paraneoplastic
      neurologic disorders. We used a human brain cDNA expression library and serum
      from a paraneoplastic neurologic disorder patient to search for new autoantigens
      in the nervous system. Pyridoxal phosphatase was identified as a novel
      autoantigen. Expression studies showed that pyridoxal phosphatase was strongly
      expressed in various parts of the central nervous system. Sera contained
      antibodies against pyridoxal phosphatase in 22 of 243 (9.1%) patients with lung
      cancer and eight of 113 (7.1%) with other forms of cancer vs two of 88 (2.3%)
      healthy control subjects. In addition, 2-4% of patients with different autoimmune
      diseases had autoantibodies against pyridoxal phosphatase. None of the
      antipyridoxal phosphatase-positive patients were known to have a paraneoplastic
      neurologic disorder. Hence, autoantibodies against pyridoxal phosphatase
      correlate with cancer but not necessarily with the subset of patients with
      paraneoplastic neurological disorders although serum from such a patient was used
      to screen the cDNA library. This study showed that yet another enzyme involved in
      pyridoxal 5'-phosphate metabolism is an autoantigen. Thus, pyridoxal 5'-phosphate
      seems to be a common denominator for autoantigens involved in autoimmune
      diseases.

PMID- 15452548
TI  - Targeting the p53-MDM2 interaction to treat cancer.
AB  - The tumour suppressor p53 is a transcription factor with powerful antitumour
      activity that is controlled by its negative regulator MDM2 (mouse double minute
      2, also termed HDM2 in humans) through a feedback mechanism. MDM2, which is
      overproduced in many tumours, binds p53 and inhibits its function by modulating
      its transcriptional activity and stability. Activation of p53 in tumour cells by
      inhibiting its physical interaction with MDM2 has been in the focus of cancer
      drug discovery. However, development of nonpeptidic MDM2 antagonists turned out
      to be challenging. Recently, the first potent and selective small-molecule
      antagonists of MDM2, the Nutlins, have been identified. Studies with Nutlins
      provided in vitro and in vivo proof-of-principle for targeting p53-MDM2
      interaction for cancer therapy.

PMID- 15452549
TI  - Characterisation of molecular events following cisplatin treatment of two curable
      ovarian cancer models: contrasting role for p53 induction and apoptosis in vivo.
AB  - The detailed molecular basis and determinants of in vivo tumour sensitivity to
      conventional anticancer agents remain unclear. We examined the cellular and
      molecular consequences of cisplatin treatment using two ovarian tumour xenograft
      models that had not been previously adapted to culture in vitro. Both xenografts
      were curable with clinically relevant multiple doses of cisplatin. Following a
      single dose of cisplatin (6 mg kg(-1) i.p.) growth delays of 25 and 75 days were
      obtained for pxn100 and pxn65, respectively. This difference in response was not
      due to differences in DNA damage. Pxn100 tumours had a functional p53 response
      and a wild-type p53 sequence, whereas pxn65 harboured a mutant p53 and lacked a
      functional p53 response. Microarray analysis revealed the induction of p53
      regulated genes and regulators of checkpoint control and apoptosis in pxn100
      tumours following cisplatin-treatment. By contrast, there was no p53-dependent
      response and only limited changes in gene expression were detected in the pxn65
      tumours. TUNEL analysis demonstrated high levels of apoptosis in the pxn100
      tumours following cisplatin treatment, but there was no detectable apoptosis in
      the pxn65 tumours. Our observations show that a marked in vivo response to
      cisplatin can occur via p53-dependent apoptosis or independently of p53 status in
      human ovarian xenografts.

PMID- 15452550
TI  - Phase I dose-escalation trial of irinotecan with continuous infusion 5-FU first
      line, in metastatic colorectal cancer.
AB  - This single-centre phase I trial was designed to determine the maximum tolerated
      dose of irinotecan and the recommended dose to use in combination with a fixed
      dose of 5-fluorouracil (5-FU) administered as a protracted venous infusion, for
      the first-line treatment of metastatic colorectal cancer (CRC). Tolerability and
      efficacy were secondary end points. In all, 22 patients, median age 57 years,
      were treated with escalating, weekly doses of irinotecan (50, 75, 100 and 85 mg
      m(-2)) in combination with 250 mg m(-2) 5-FU administered as a continuous
      infusion. All patients had measurable disease. The combination was well tolerated
      up to an irinotecan dose of 75 mg m(-2). However, three out of five patients at
      the 100 mg m(-2) irinotecan dose level had their dose reduced due to multiple
      grade 2 toxicities, and eventually one patient stopped treatment due to grade 3
      diarrhoea and multiple grade 2 toxicities. Subsequent patients were recruited at
      an irinotecan dose level of 85 mg m(-2). The overall response rate was 55%,
      comprising one complete and 11 partial responses (PRs). Six patients also
      achieved sustained stable disease (SD), giving a clinical benefit (complete
      response/PR/SD) response of 82%. The median duration of response was 238 days
      (8.5 months) and median time to progression was 224 days (8.0 months). Two
      patients who achieved PRs underwent partial hepatectomies. Thus, irinotecan (85
      mg m(-2)) combined with a continuous infusion of 5-FU (250 mg m(-2)) is an active
      and well-tolerated regimen for the treatment of metastatic CRC. It represents an
      effective treatment for patients who require close supervision and support,
      throughout their initial exposure to chemotherapy for this disease, and this dose
      combination was recommended for an ongoing phase II study.

PMID- 15452551
TI  - Phase I and pharmacokinetic study of XR11576, an oral topoisomerase I and II
      inhibitor, administered on days 1-5 of a 3-weekly cycle in patients with advanced
      solid tumours.
AB  - XR11576 is an oral topoisomerase I and II inhibitor. The objectives of this phase
      I study were to assess the dose-limiting toxicities (DLTs), to determine the
      maximum tolerated dose (MTD) and to describe the pharmacokinetics (PKs) of
      XR11576 when administered orally on days 1-5 every 3 weeks to patients with
      advanced solid tumours. Patients were treated with escalating doses of XR11576 at
      doses ranging from 30 to 180 mg day(-1). For PK analysis, plasma sampling was
      performed during the first and second courses of treatment and XR11576
      concentrations were assayed using a validated high-performance liquid
      chromatographic assay with mass spectrometric detection. In all, 21 patients
      received a total of 47 courses. The MTD was reached at 180 mg day(-1), with
      diarrhoea and fatigue as DLT. Nausea and vomiting, although not qualifying for
      DLT, was ubiquitous. Only in combination with an extensive prophylactic
      antiemetic regimen consisting of a combination of both dexamethasone and a 5HT3
      antagonist was treatment with XR11576 at 120 mg day(-1) tolerable. The systemic
      exposure of XR11576 increased more than proportionally with increasing dose, with
      a large interpatient variability. No objective responses were seen; four patients
      experienced stable disease for periods of 12-30 weeks. In this study, the DLTs of
      XR11576 were diarrhoea and fatigue. The recommended dose for phase II studies of
      XR11576 is 120 mg administered orally, on days 1-5 every 21 days. Alternative
      regimens are currently being explored.

PMID- 15452552
TI  - Identification of single-nucleotide polymorphisms of the human neurokinin 1
      receptor gene and pharmacological characterization of a Y192H variant.
AB  - Neurokinin receptors in the central nervous system are involved in the neural
      circuitry of anxiety, depression and emesis. This has led to the development of
      nonpeptidic NK1 receptor antagonists as therapeutic agents. Clinical trials have
      shown that NK1 receptor antagonists have efficacy in chemotherapy-induced emesis
      and depression. Sequence polymorphisms can potentially influence the efficacy of
      drugs in patient populations and are an important consideration in the drug
      development process. To identify DNA sequence variants in the NK1 receptor,
      comparative DNA sequencing was performed on a population of 93 individuals. In
      total, 19 single-nucleotide polymorphisms (SNPs) were identified with one SNP
      (g.78351T>C) resulting in a tyrosine to histidine substitution at residue 192
      (Y192H). The Y192H variant was expressed using site-directed mutagenesis and was
      characterized with respect to affinity, receptor kinetics, functional calcium
      response and receptor internalization. In all cases the Y192H variant was found
      to display properties similar to those of the wild-type receptor.

PMID- 15452553
TI  - Lower frequency of CYP2C9*2 in Mexican-Americans compared to Spaniards.
AB  - Interethnic differences in cytochrome P450 polymorphism might be responsible, at
      least in part, for the variations in drug disposition between ethnic groups. Of
      the various CYP2C9 alleles, CYP2C9*2 and CYP2C9*3 have been reported to have
      altered catalytic activities compared to the wild-type CYP2C9*1. The present
      study is aimed at analysing the CYP2C9 polymorphism in a Mexican-American
      compared with a Spanish population. Differences between the two populations of
      healthy volunteers, Mexican-Americans (n=98 subjects) and Spaniards (n=102
      subjects), regarding the CYP2C9 allele frequencies have been found. CYP2C9
      genotypes among the studied Mexican-American population are in equilibrium. The
      95% CI were, respectively, 0.81-0.90 for CYP2C9*1 (n=169), 0.05-0.13 for CYP2C9*2
      (n=16) and 0.031-0.10 for CYP2C9*3 (n=11). CYP2C9*4, *5 and *6 were found in none
      of the studied subjects. The frequency of CYP2C9*2 was lower among Mexican
      Americans compared to Spaniards (P<0.05). The obtained frequency of CYP2C9
      alleles is compatible with the genomic assembly of the constitutive potential
      ethnic origin of this population, and supports the need of pharmacogenetic
      studies for optimizing the recommended drug dosages to Mexican-Americans.

PMID- 15452554
TI  - Principles and results of high-intensity focused ultrasound for localized
      prostate cancer.
AB  - Focused ultrasound holds promise in a large number of therapeutic applications.
      It has long been known that high-intensity focused ultrasound (HIFU) can kill
      tissue through coagulative necrosis. However, it is only in recent years that
      practical clinical applications are becoming possible, with the development of
      high-power ultrasound arrays and noninvasive monitoring methods. In the last
      decade, HIFU have been adapted and used to treat localized prostate cancer and it
      is now commercially available in Europe. In this article, preclinical studies and
      clinical development of prostate HIFU as well as early clinical results from our
      center and international studies are reviewed. Early results demonstrated that
      prostate HIFU is efficient to obtain local control for low- and intermediate-risk
      localized prostate cancer; however, long-term follow-up is still needed to
      estimate the efficacy of prostate HIFU in terms of specific cancer mortality.
      This makes HIFU a viable alternative in patients not candidate for radical
      therapy.

PMID- 15452555
TI  - 5alpha-Androstane-3alpha,17beta-diol activates pathway that resembles the
      epidermal growth factor responsive pathways in stimulating human prostate cancer
      LNCaP cell proliferation.
AB  - 5alpha-Androstane-3alpha,17beta-diol (3alpha-diol) is considered to have no
      androgenic effects in androgen target organs unless it is oxidized to 5alpha
      dihydrotestosterone (5alpha-DHT). We used microarray and bioinformatics to
      identify and compare 3alpha-diol and 5alpha-DHT responsive gene in human prostate
      LNCaP cells. Through a procedure called 'hypervariable determination', a similar
      set of 30 responsive genes involving signal transduction, transcription
      regulation, and cell proliferation were selected in 5alpha-DHT-, 3alpha-diol-,
      and epidermal growth factor (EGF)-treated samples. F-means cluster and networking
      procedures showed that the responsive pattern of these genes was more closely
      related between 3alpha-diol and EGF than between 5alpha-DHT and 3alpha-diol
      treatments. We conclude that 3alpha-diol is capable of stimulating prostate cell
      proliferation by eliciting EGF-like pathway in conjunction with androgen receptor
      pathway.

PMID- 15452556
TI  - The politics of science.

PMID- 15452557
TI  - Grabbing E2 by the tail.

PMID- 15452558
TI  - Double duty.

PMID- 15452559
TI  - Out of hot water.

PMID- 15452560
TI  - Arginine methylation signals mRNA export.

PMID- 15452561
TI  - RNA editing of a human potassium channel modifies its inactivation.

PMID- 15452563
TI  - The ATP switch model for ABC transporters.
AB  - ABC transporters mediate active translocation of a diverse range of molecules
      across all cell membranes. They comprise two nucleotide-binding domains (NBDs)
      and two transmembrane domains (TMDs). Recent biochemical, structural and genetic
      studies have led to the ATP-switch model in which ATP binding and ATP hydrolysis,
      respectively, induce formation and dissociation of an NBD dimer. This provides an
      exquisitely regulated switch that induces conformational changes in the TMDs to
      mediate membrane transport.

PMID- 15452564
TI  - The promise of stem cells.

PMID- 15452565
TI  - Brain scam?

PMID- 15452567
TI  - Dopamine: should I stay or should I go now?

PMID- 15452568
TI  - Ancient viral protein enrages astrocytes in multiple sclerosis.

PMID- 15452569
TI  - Antisense inhibition of reward learning.

PMID- 15452570
TI  - Moving to a different beat.

PMID- 15452571
TI  - Francis crick 1916-2004.

PMID- 15452572
TI  - The sexual brain.

PMID- 15452573
TI  - Ethics and social policy in research on the neuroscience of human sexuality.
AB  - The potential benefits of neuroscientific research into sexuality are great, but
      neuroscientists must participate in debates over the social, forensic and
      therapeutic implications of their findings. If serious research in sexuality is
      to be supported by the public, researchers must continue to earn society's trust
      with responsible and thoughtful presentation of their work.

PMID- 15452574
TI  - Sexual differentiation of the vertebrate nervous system.
AB  - Understanding the mechanisms that give rise to sex differences in the behavior of
      nonhuman animals may contribute to the understanding of sex differences in
      humans. In vertebrate model systems, a single factor-the steroid hormone
      testosterone-accounts for most, and perhaps all, of the known sex differences in
      neural structure and behavior. Here we review some of the events triggered by
      testosterone that masculinize the developing and adult nervous system, promote
      male behaviors and suppress female behaviors. Testosterone often sculpts the
      developing nervous system by inhibiting or exacerbating cell death and/or by
      modulating the formation and elimination of synapses. Experience, too, can
      interact with testosterone to enhance or diminish its effects on the central
      nervous system. However, more work is needed to uncover the particular cells and
      specific genes on which testosterone acts to initiate these events.

PMID- 15452575
TI  - The neural basis of puberty and adolescence.
AB  - The pubertal transition to adulthood involves both gonadal and behavioral
      maturation. A developmental clock, along with permissive signals that provide
      information on somatic growth, energy balance and season, time the awakening of
      gonadotropin releasing hormone (GnRH) neurons at the onset of puberty. High
      frequency GnRH release results from disinhibition and activation of GnRH neurons
      at puberty onset, leading to gametogenesis and an increase in gonadal steroid
      hormone secretion. Steroid hormones, in turn, both remodel and activate neural
      circuits during adolescent brain development, leading to the development of
      sexual salience of sensory stimuli, sexual motivation, and expression of
      copulatory behaviors in specific social contexts. These influences of hormones on
      reproductive behavior depend in part on changes in the adolescent brain that
      occur independently of gonadal maturation. Reproductive maturity is therefore the
      product of developmentally timed, brain-driven and recurrent interactions between
      steroid hormones and the adolescent nervous system.

PMID- 15452576
TI  - The neurobiology of pair bonding.
AB  - A neurobiological model for pair-bond formation has emerged from studies in
      monogamous rodents. The neuropeptides oxytocin and vasopressin contribute to the
      processing of social cues necessary for individual recognition. Mesolimbic
      dopamine is involved in reinforcement and reward learning. Concurrent activation
      of neuropeptide and dopamine receptors in the reward centers of the brain during
      mating results in a conditioned partner preference, observed as a pair bond.
      Differential regulation of neuropeptide receptor expression may explain species
      differences in the ability to form pair bonds. These and other studies discussed
      here have intriguing implications for the neurobiology of social attachment in
      our own species.

PMID- 15452578
TI  - Human endogenous retrovirus glycoprotein-mediated induction of redox reactants
      causes oligodendrocyte death and demyelination.
AB  - Human endogenous retroviruses (HERVs) constitute 8% of the human genome and have
      been implicated in both health and disease. Increased HERV gene activity occurs
      in immunologically activated glia, although the consequences of HERV expression
      in the nervous system remain uncertain. Here, we report that the HERV-W encoded
      glycoprotein syncytin is upregulated in glial cells within acute demyelinating
      lesions of multiple sclerosis patients. Syncytin expression in astrocytes induced
      the release of redox reactants, which were cytotoxic to oligodendrocytes.
      Syncytin-mediated neuroinflammation and death of oligodendrocytes, with the
      ensuing neurobehavioral deficits, were prevented by the antioxidant ferulic acid
      in a mouse model of multiple sclerosis. Thus, syncytin's proinflammatory
      properties in the nervous system demonstrate a novel role for an endogenous
      retrovirus protein, which may be a target for therapeutic intervention.

PMID- 15452577
TI  - Essential role of Ca2+-binding protein 4, a Cav1.4 channel regulator, in
      photoreceptor synaptic function.
AB  - CaBP1-8 are neuronal Ca(2+)-binding proteins with similarity to calmodulin (CaM).
      Here we show that CaBP4 is specifically expressed in photoreceptors, where it is
      localized to synaptic terminals. The outer plexiform layer, which contains the
      photoreceptor synapses with secondary neurons, was thinner in the Cabp4(-/-) mice
      than in control mice. Cabp4(-/-) retinas also had ectopic synapses originating
      from rod bipolar and horizontal cells tha HJt extended into the outer nuclear
      layer. Responses of Cabp4(-/-) rod bipolars were reduced in sensitivity about 100
      fold. Electroretinograms (ERGs) indicated a reduction in cone and rod synaptic
      function. The phenotype of Cabp4(-/-) mice shares similarities with that of
      incomplete congenital stationary night blindness (CSNB2) patients. CaBP4 directly
      associated with the C-terminal domain of the Ca(v)1.4 alpha(1)-subunit and
      shifted the activation of Ca(v)1.4 to hyperpolarized voltages in transfected
      cells. These observations indicate that CaBP4 is important for normal synaptic
      function, probably through regulation of Ca(2+) influx and neurotransmitter
      release in photoreceptor synaptic terminals.

PMID- 15452579
TI  - Tuning curve sharpening for orientation selectivity: coding efficiency and the
      impact of correlations.
AB  - Several studies have shown that the information conveyed by bell-shaped tuning
      curves increases as their width decreases, leading to the notion that sharpening
      of tuning curves improves population codes. This notion, however, is based on
      assumptions that the noise distribution is independent among neurons and
      independent of the tuning curve width. Here we reexamine these assumptions in
      networks of spiking neurons by using orientation selectivity as an example. We
      compare two principal classes of model: one in which the tuning curves are
      sharpened through cortical lateral interactions, and one in which they are not.
      We report that sharpening through lateral interactions does not improve
      population codes but, on the contrary, leads to a severe loss of information. In
      addition, the sharpening models generate complicated codes that rely extensively
      on pairwise correlations. Our study generates several experimental predictions
      that can be used to distinguish between these two classes of model.

PMID- 15452580
TI  - Rhythmic arm movement is not discrete.
AB  - Rhythmic movements, such as walking, chewing or scratching, are phylogenetically
      old motor behaviors found in many organisms, ranging from insects to primates. In
      contrast, discrete movements, such as reaching, grasping or kicking, are
      behaviors that have reached sophistication primarily in younger species,
      particularly primates. Neurophysiological and computational research on arm motor
      control has focused almost exclusively on discrete movements, essentially
      assuming similar neural circuitry for rhythmic tasks. In contrast, many
      behavioral studies have focused on rhythmic models, subsuming discrete movement
      as a special case. Here, using a human functional neuroimaging experiment, we
      show that in addition to areas activated in rhythmic movement, discrete movement
      involves several higher cortical planning areas, even when both movement
      conditions are confined to the same single wrist joint. These results provide
      neuroscientific evidence that rhythmic arm movement cannot be part of a more
      general discrete movement system and may require separate neurophysiological and
      theoretical treatment.

PMID- 15452581
TI  - Recording spikes from a large fraction of the ganglion cells in a retinal patch.
AB  - To understand a neural circuit completely requires simultaneous recording from
      most of the neurons in that circuit. Here we report recording and spike sorting
      techniques that enable us to record from all or nearly all of the ganglion cells
      in a patch of the retina. With a dense multi-electrode array, each ganglion cell
      produces a unique pattern of activity on many electrodes when it fires an action
      potential. Signals from all of the electrodes are combined with an iterative
      spike sorting algorithm to resolve ambiguities arising from overlapping spike
      waveforms. We verify that we are recording from a large fraction of ganglion
      cells over the array by labeling the ganglion cells with a retrogradely
      transported dye and by comparing the number of labeled and recorded cells. Using
      these methods, we show that about 60 receptive fields of ganglion cells cover
      each point in visual space in the salamander, consistent with anatomical
      findings.

PMID- 15452582
TI  - Land of promise: challenges and opportunities for research in South Africa.

PMID- 15452586
TI  - Association analysis of mild mental impairment using DNA pooling to screen 432
      brain-expressed single-nucleotide polymorphisms.
AB  - We hypothesize that mild mental impairment (MMI) represents the low extreme of
      the same quantitative trait loci (QTLs) that operate throughout the distribution
      of intelligence. To detect QTLs of small effect size, we employed a direct
      association strategy by genotyping 432 presumably functional nonsynonymous single
      nucleotide polymorphisms (nsSNPs) identified from public databases on DNA pools
      of 288 cases and 1025 controls. In total, 288 MMI cases were identified by in
      home administration of McCarthy Scales of Children's Abilities to 836 twin pairs
      selected from a community sample of more than 14 000 children previously screened
      for nonverbal cognitive delay using parentally administered tests. Controls were
      selected from the community sample representing the full range of nonverbal
      intelligence. SNPs showing at least 7% allele frequency differences between case
      and control DNA pools were tested for their association with the full range of
      nonverbal intelligence using five DNA subpools, each representing quintiles of
      the normal quantitative trait scores from the 1025 controls. SNPs showing linear
      associations in the expected direction across quintiles using pooled DNA were
      individually genotyped for the 288 cases and 1025 controls and analyzed using
      standard statistical methods. One SNP (rs1136141) in HSPA8 met these criteria,
      yielding a significant (P=0.036) allelic frequency difference between cases and
      controls for individual genotyping and a significant (P=0.013) correlation within
      the control group that accounts for 0.5% of the variance. The present SNP
      strategy combined with DNA pooling and large samples represents a step towards
      identifying QTLs of small effect size associated with complex traits in the
      postgenomic era when all functional polymorphisms will be known.

PMID- 15452587
TI  - Sex-specific association between bipolar affective disorder in women and GPR50,
      an X-linked orphan G protein-coupled receptor.
AB  - GPR50 is an orphan G protein-coupled receptor (GPCR) located on Xq28, a region
      previously implicated in multiple genetic studies of bipolar affective disorder
      (BPAD). Allele frequencies of three polymorphisms in GPR50 were compared in case
      control studies between subjects with BPAD (264), major depressive disorder (MDD)
      (226), or schizophrenia (SCZ) (263) and ethnically matched controls (562).
      Significant associations were found between an insertion/deletion polymorphism in
      exon 2 and both BPAD (P=0.0070), and MDD (P=0.011) with increased risk associated
      with the deletion variant (GPR50(Delta502-505)). When the analysis was restricted
      to female subjects, the associations with BPAD and MDD increased in significance
      (P=0.00023 and P=0.0064, respectively). Two other single-nucleotide polymorphisms
      (SNPs) tested within this gene showed associations between: the female MDD group
      and an SNP in exon 2 (P=0.0096); and female SCZ and an intronic SNP (P=0.0014).
      No association was detected in males with either MDD, BPAD or SCZ. These results
      suggest that GPR50(Delta502-505), or a variant in tight linkage disequilibrium
      with this polymorphism, is a sex-specific risk factor for susceptibility to
      bipolar disorder, and that other variants in the gene may be sex-specific risk
      factors in the development of schizophrenia.

PMID- 15452588
TI  - The role of allogeneic transplantation in high-risk acute myelogenous leukemia.
AB  - Patients with high-risk acute myelogenous leukemia (AML) in first remission are
      at increased risk for disease recurrence and are often considered for allogeneic
      bone marrow transplantation (BMT) if there is a suitable HLA-identical sibling
      donor. Analysis of results from randomized clinical trials comparing different
      treatment strategies for patients with AML (chemotherapy, autologous BMT, and
      allogeneic BMT) suggests that allogeneic BMT may be a superior treatment modality
      for patients in the high-risk subgroup. Interpretation of clinical trial results,
      however, is problematic due to poor compliance with transplant options, absence
      of studies specifically designed to addresses this question, and ongoing
      redefinition of the high-risk subgroup. Alternative allogeneic transplant
      approaches to reduce toxicity from graft-versus-host disease and enhance graft
      versus-leukemia reactivity may offer therapeutic promise in this patient
      population.

PMID- 15452590
TI  - The health behaviours of secondary school students in New South Wales 2002.

PMID- 15452591
TI  - Effect of blockers of potential-dependent and calcium-activated K+-channels on
      facilitation of neuromuscular transmission.
AB  - Rhythmic stimulation of nerve-muscle preparation of frog sternal muscle bathed in
      low-Ca(2+) saline increased the release of neurotransmitter (facilitation) and
      modified the shape of extracellular response of nerve terminal (decreased phase
      III amplitude). Iberiotoxin and 4-aminopyridine modified the dynamics these
      processes. We conclude that inactivation of potential-dependent K(+)-channels and
      activation of calcium-dependent K(+)-channels in frog motor nerve terminals
      during rhythmic activity modulate Ca(2+) influx into nerve terminals and
      contribute into facilitation of neurotransmitter secretion. The degree of these
      mechanisms depends on the rate of synaptic rhythmic activity.

PMID- 15452592
TI  - Biochemical indexes of the skin and blood melatonin concentration in rats during
      acute stress and treatment with exogenous melatonin.
AB  - We studied the effect of acute stress on serum melatonin concentration, content
      of major components in the connective tissue (uronic acids, hexosamines, and
      hydroxyproline), and beta-galactosidase activity in the skin of rats with
      different activity in the open-field test receiving intraperitoneal injections of
      physiological saline or melatonin. Acute stress intensified catabolism of
      carbohydrate components and affected characteristics of the main skin
      biopolymers. The content of uronic acids in connective tissue carbohydrates
      decreased. Collagen structures of the skin underwent less pronounced changes. The
      observed changes were similar in behaviorally active and passive animals.
      Administration of melatonin increased the contents of uronic acids and
      hexosamines in the skin. Pretreatment with melatonin prevented the decrease in
      the content of glycosaminoglycans in rat skin during acute stress.

PMID- 15452593
TI  - Morphological and functional state of rat ovaries in early and late periods after
      administration of platinum cytostatics.
AB  - Experiments on Wistar rats showed that cisplatin and carboplatin induced similar
      morphological alterations in the ovaries. Both agents reduced the number of
      structural and functional elements, but the effect of cisplatin was more
      pronounced. Morphological changes observed in the early period after injection of
      the preparations were accompanied by prolongation of the estrous cycle, which was
      longer in rats treated with carboplatin. Partial and reversible sterility was
      observed in females at the early terms after cisplatin treatment.

PMID- 15452594
TI  - Mechanisms of pefloxacin-induced pain.
AB  - In electrophysiological and behavioral experiments on rats we studied the effects
      of pefloxacin, a member of fluoroquinolone family, on the nociceptive system.
      Intraperitoneal injection of pefloxacin (80 mg/kg) decreased the thresholds of
      nociceptive response to noxious stimulation in the hot-plate test. In addition,
      it decreased the threshold of the late component of nociceptive flexor reflex.
      Intrathecal application of pefloxacin in a dose of 20 microg provoked allodynia,
      while the higher dose of 400 microg induced behavioral pattern characteristic of
      central pain syndrome. It was hypothesized that pain induced by pefloxacin
      results from disturbances in GABAergic inhibition in the central subdivisions of
      the nociceptive system.

PMID- 15452595
TI  - Serotoninergic nervous system of the heart and abdominal organs during functional
      load and pathology.
AB  - We studied the involvement of serotoninergic system into postprandial motility of
      the stomach and small intestine and into the development of experimental
      myocarditis and stomach ulcer. Gradual increase in activity of this system was
      observed under pathological conditions.

PMID- 15452596
TI  - Half-life of leu-enkephalin in the serum of infants of the first year of life on
      different types of feeding: relationship with temperament.
AB  - The half-life of leu-enkephalin in the serum of infants aged under 1 year is
      significantly shorter than in adults. In girls leu-enkephalin half-life is
      significantly longer than in boys. The half-life of leu-enkephalin is different
      in infants on breast and formula feeding. Nine characteristics of temperament in
      infants of the first year of life were determined using EITQ and ITQ
      questionnaires. Serum leu-enkephalin half-life directly correlated with
      temperament characteristics (activity, perception, threshold), but not with the
      level psychomotor development.

PMID- 15452597
TI  - Effect of neonatal handling in rats with hereditary stress-induced arterial
      hypertension (NISAG rats).
AB  - NISAG rats were subjected to handling on days 1-21 after birth. Blood pressure
      and plasma corticosterone concentration were measured in 6-month-old handled and
      control NISAG rats at rest and under stress conditions. Animal behavior was
      studied in the open-field test. Handling had no effect on body weight and
      relative weights of the heart and adrenal glands. In rats subjected to handling,
      changes in blood pressure and adrenal cortex produced by acute emotional stress
      (30-min restriction) were less pronounced than in control animals. Handled rats
      demonstrated less fear in a new environment and exhibited high exploratory
      activity in the open-field test. Our findings suggest that neonatal handling
      reduces stress reactivity and decreases the severity of hypertension in adult
      NISAG rats.

PMID- 15452598
TI  - Human neural stem cells normalize rat behavior after hypoxia.
AB  - Transplants of cultured neural stem cells from human brain survived, retained
      multipotent activity, and produced a neuroprotective effect on degenerating
      neurons in the brain of adult rats subjected to hypoxic hypoxia. They normalized
      animal behavior and improved conditioning in two-way avoidance response paradigm
      in a shuttle box.

PMID- 15452599
TI  - Free radical oxidation and catalytic activity of aconitate hydratase in rat liver
      under normal conditions and during toxic hepatitis.
AB  - We observed intensification of free radical oxidation, decrease in activity, and
      changes in catalytic properties of aconitate hydratase in the liver of rats with
      toxic hepatitis. The total yield and maximum flash intensity of
      biochemiluminescence increased by 2.2 and 1.7 times, respectively. Differences
      were revealed in the regulation of aconitate hydratase activity with Fe(2+),
      Ca(2+), H(2)O(2), and oxidized and reduced glutathione in the liver of rats with
      toxic hepatitis and control animals.

PMID- 15452600
TI  - Effect of low-energy laser irradiation on the area of experimental myocardial
      infarction, lipid peroxidation, and hemoglobin affinity for oxygen.
AB  - The mechanism of antiischemic effect of low-energy laser radiation was studied in
      rats with experimental myocardial infarction taking into consideration the effect
      of laser on hemoglobin affinity for oxygen and intensity of lipid peroxidation.
      Low-energy laser irradiation for 15 min in vitro decreased the area of myocardial
      infarction, slightly reduced hemoglobin affinity for oxygen, and inhibited lipid
      peroxidation. Short-term low-energy laser irradiation did not reduce the area of
      necrosis, initiated lipid peroxidation, and increased superoxide dismutase
      activity.

PMID- 15452601
TI  - Fibrinogen and its oxidized form induce interleukin-8 [correction of interleukin
      2] production in cultured endothelial cells of human vessels.
AB  - Oxidized fibrinogen was more potent than native fibrinogen in inducing
      interleukin-8 production in primary culture of human endothelial cells. The
      optimal concentration of oxidized fibrinogen was 3 mg/ml. The optimal time of UV
      irradiation was 17 min. Secretion of interleukin-8 was maximum during culturing
      of endothelial cells in a serum-free medium.

PMID- 15452602
TI  - Identification of exocytosis mediator proteins in peripheral blood neutrophils of
      patients with chronic myeloid leukemia.
AB  - We demonstrated expression of plasma membrane proteins (syntaxin-4 and syntaxin
      6) and specific/gelatinase granule membrane proteins (SNAP-25 and VAMP-2) in the
      peripheral blood neutrophils of patients with chronic myeloid leukemia. VAMP-1
      associated with membranes of azurophilic and specific/gelatinase granules was
      absent in peripheral blood neutrophils of patients with chronic myeloid leukemia.
      Decreased capacity of neutrophils to exocytosis in chronic myeloid leukemia is
      probably caused by the absence of VAMP-1 in these cells.

PMID- 15452603
TI  - Effects of low-intensity ultrahigh frequency electromagnetic radiation on
      inflammatory processes.
AB  - Low-intensity ultrahigh frequency electromagnetic radiation (42 GHz, 100
      microW/cm(2)) reduces the severity of inflammation and inhibits production of
      active oxygen forms by inflammatory exudate neutrophils only in mice with
      inflammatory process. These data suggest that some therapeutic effects of
      electromagnetic radiation can be explained by its antiinflammatory effect which
      is realized via modulation of functional activity of neutrophils in the focus of
      inflammation.

PMID- 15452604
TI  - Binding of Fc receptors on blood T and B cells with IgG from healthy cows and
      cows with chronic lympholeukemia.
AB  - Pure population of T and B cells was obtained by a combined method consisting in
      lymphocyte fractionation through Nylon wool and precipitation of E-rosettes in
      17% Verograffin density gradient. Scatchard analysis showed that T and B cells
      isolated from the blood of healthy cattle bind similar quantities of IgG
      molecules. Binding of IgG to Fc receptors of T and B cell isolated from animals
      with chronic lympholeukemia increases. The expression of Fc receptors for IgG is
      changed in cattle with chronic lympholeukemia.

PMID- 15452605
TI  - Requirement and criteria of adequate vitamin supply in healthy newborns.
AB  - Studies of the relationship between urinary excretion of vitamins and their daily
      intake in healthy newborns showed that babies aged 3-10 days should receive 30 mg
      vitamin C, 0.24 mg vitamin B(2), and 0.13 mg vitamin B(1). The criteria of
      adequate vitamin C, B(1), and B(2) supply evaluated by their urinary excretion
      are 220.0, 0.7, and 1.4 mg/g excreted creatinine, respectively.

PMID- 15452606
TI  - Composition of protein-peptide complex of human fetal and rabbit juvenile
      tissues.
AB  - The composition of the protein-peptide complex of cryopreserved human fetal
      tissues and juvenile tissues of newborn rabbits was studied by spectrophotometric
      and chromatographic methods (liquid, thin layer, and reaction paper
      chromatography).

PMID- 15452607
TI  - Effect of dimephosphone (monophosphonate) on the course of pregnancy and fetal
      development in rats.
AB  - Dimephosphone injected on days 1-19 of gestation did not cause fetal death and
      specific abnormalities in rats and did not modulate sex differentiation of
      fetuses. Morphological study of fetal liver revealed no pathological changes.

PMID- 15452608
TI  - Modification of biological activity of lipopolysaccharide in the complex with
      chitosan.
AB  - In the complex with chitosan, lipopolysaccharide partially lost its ability to
      induce lymphokines tumor necrosis factor and interleukin-8, but retained
      immunostimulating properties and increased phagocytic function of macrophages by
      improving digestion of bacteria.

PMID- 15452609
TI  - Effect of monoamine oxidase gene knockout on dopamine metabolism in mouse brain
      structures.
AB  - Experiments were performed on knockout Tg8 mice lacking monoamine oxidase A gene
      that plays a major role in dopamine catabolism. The study by the method of high
      performance liquid chromatography revealed considerable regional differences in
      the contents of dopamine and its metabolite dihydroxyphenylacetic acid in brain
      structures of these animals. Tg8 mice differed from the parent C3H/HeJ strain by
      low level of dihydroxyphenylacetic acid in the striatum, midbrain, hypothalamus,
      and hippocampus and high concentration of dopamine in the striatum. No
      differences were revealed in the contents of dopamine and dihydroxyphenylacetic
      acid in the frontal cortex and amygdala. The 2.4-4.8-fold decrease in the content
      of dihydroxyphenylacetic acid in various brain structures was not accompanied by
      changes in dopamine concentration. These data reflect the effective compensation
      for deficiency of dopamine metabolism. Our results suggest that monoamine
      oxidases A and B and catechol-O-methyltransferase play different roles in
      dopamine metabolism in various brain structures.

PMID- 15452610
TI  - Expression of surface lymphocyte markers in various courses of gastrointestinal
      tumors.
AB  - Expression of activation antigens increased in patients with gastrointestinal
      tumors of various clinical courses. The count of CD25+ and CD71+ lymphocytes was
      high in patients with favorable course of non-progressive tumors. The increase in
      the expression of activation markers probably reflects adequate functional
      activity of the immune system in patients with tumors.

PMID- 15452611
TI  - Effect of peptide preparation epithalamin on circadian rhythm of epiphyseal
      melatonin-producing function in elderly people.
AB  - Circadian rhythm of plasma melatonin concentrations in healthy elderly subjects
      was studied before and after a course treatment with Epithalamin (peptide
      preparation from the pineal gland). Epithalamin modulated the melatonin-producing
      function of the pineal gland. During the dark period plasma melatonin
      concentration increased in subjects with initially lowered activity of the pineal
      gland, while in subjects with normal epiphyseal function plasma melatonin
      concentration tended to decrease.

PMID- 15452612
TI  - Initial morphofunctional asymmetry of the adrenal glands in CBA/Lacy mice.
AB  - We performed morphological examination of the adrenal glands from intact CBA/Lacy
      mice. Morphometry, histochemistry, and electron microscopy revealed predominance
      of functional activity of the right adrenal gland. This phenomenon was associated
      with adaptive state of the animals. The observed differences are probably related
      to specific pattern of functioning of paired organs determined during
      embryogenesis.

PMID- 15452613
TI  - Autoradiographic study of parasympathetic paragangliomas (chemodectomas) of the
      neck.
AB  - Study of the morphofunctional characteristics of chemodectomas of the neck by
      photoautoradiography (semithin sections) showed the absence of protein-producing
      and proliferative activity in light and dark tumor cells against the background
      of strained biosynthetic processes in stromal cells. Invasion of capillary walls
      by tumor cells with their release into the capillary lumen is a prerequisite for
      metastases of these tumors.

PMID- 15452614
TI  - Pathomorphological criteria for cardiosclerosis and angioarchitectonics of the
      hypertrophic myocardium in hypertensive heart.
AB  - We performed a pathomorphological study of 200 hearts with cicatricial changes
      from patients died from hypertensive disease. Most postinfarction scars in men
      were transmural and localized in the anterior and posterior wall of the left
      ventricle and in the interventricular septum. Non-transmural scars were revealed
      in the lateral wall (primarily in women). Pathognomonic changes in the
      architectonics of the heart included reduction of regional blood flow and
      segmentary, discontinuously extended, and diffusely extended atherosclerotic
      obstruction. Changes in the index of blood supply to the myocardium corresponded
      to pronounced decrease in vascularization of the hypertrophic left ventricle. A
      correlation was found between the index of blood supply to the myocardium and
      mean systolic and diastolic blood pressure. Therefore, the coronary bed did not
      satisfy the demands of hypertensive heart with cicatricial changes.

PMID- 15452615
TI  - Ultrastructural evidence of invasive activity of Vibrio cholerae.
AB  - The development of experimental cholera in suckling rabbits is associated with
      typical cholerogenic syndrome: the presence of Vibrio cholerae in the blood, bile
      (in 60 and 70% cases, respectively), small and large intestine (in 100% cases).
      Simultaneously with enterocyte desquamation and increased permeability of the
      blood-enterocyte barrier, the vibrios are released into villous stroma and then
      into the microcirculatory bed. the zot toxin is involved in the mechanism of
      Vibrio cholerae invasion, the corresponding gene is present in the genome of the
      studied strain.

PMID- 15452616
TI  - Psoriasis associated with opisthorchiasis under conditions of anthelmintic
      therapy.
AB  - Biopsy specimens from patients with psoriasis concomitant with chronic
      opisthorchiasis were examined. Severe clinical course of combined disease was
      associated with degenerative changes in epidermocytes, keratinization disorders,
      and diffuse inflammatory cell infiltration of the derma. Combined therapy
      including anthelmintic agents produced a positive effect: decreased the degree of
      acanthosis, increased intracellular regeneration of epidermocytes, and suppressed
      inflammatory reaction of the derma and hyperplasia of immunocompetent cells.
      These data attested to an important role of opisthorchiasis in the pathogenesis
      of psoriatic disease.

PMID- 15452617
TI  - Effects of cytoflavin and neuronol on morphological changes in the brain and
      survival of rats with ischemic disturbances in cerebral blood flow.
AB  - Cytoflavin and neuronol produce vasoactive and neuroprotective effects in rats
      with cerebral ischemia. Vasoactive activity of neuronol was higher than that of
      cytoflavin. These differences were most pronounced at the level of
      microcirculation. Test preparations were equally potent in producing the
      neuroprotective effect. Cytoflavin and neuronol markedly decreased the mortality
      rate of animals. Over the first 6 h of ischemia the relative effectiveness of
      cytoflavin was higher than that of neuronol. However, neuronol exceeded
      cytoflavin in the relative effectiveness during the follow-up period (days 1-21).

PMID- 15452618
TI  - Immunohistochemical study of fetal stem/progenitor cells from human brain
      transplanted into traumatized spinal cord of adult rats.
AB  - Neural stem/progenitor cells from human fetal brain were grown in a tissue
      culture and transplanted into traumatized spinal cord of adult rats. The behavior
      and differentiation of transplanted cells were studied morphologically by means
      of histological and immunohistochemical methods and confocal microscopy. Human
      neural stem/progenitor cells were viable for not less than 3 months. They
      migrated and differentiated into neurons and glia in the traumatized spinal cord
      of adult rats.

PMID- 15452619
TI  - Roller organotypic cultures of postnatal rat retina.
AB  - Floating retinal sections from 7-12-day-old rats form ball-shaped retinal bodies
      during roller culturing. Histological studies of serial sections of retinal
      bodies showed that their outer surface is formed by the retina completely
      retaining organotypic cytoarchitectonics. Some retinal bodies have laminar
      structure consisting of several layers of the retina. At the initial stages of
      culturing some retinal bodies contain a cavity, which later is completely
      obliterated due to the growth of axons of ganglion cells and migration of glial
      cells and fibroblasts. This study demonstrated the possibility of long-term
      survival, differentiation, and in vitro axonal regeneration of ganglion cells,
      the main retinal efferent neurons, which can provide the basis for investigation
      of pathology and drug correction of injuries and stimulation of regeneration of
      these cells in experimental glaucoma models.

PMID- 15452620
TI  - Schizophrenic electrons in ruthenium-based oxides.
AB  - Ruthenium and oxygen form many ternary compounds in which the Ru 4d states and O
      2p states are strongly hybridized. In some such compounds, this hybridization
      leads to the loss of local magnetic moment character for the Ru, and in others it
      does not. The factors that determine which is the case are often subtle and
      poorly understood. The richness of structure types seen in ternary Ru oxides
      leads to a corresponding richness in electronic and magnetic properties. This
      article briefly describes the author's current views on these materials.

PMID- 15452621
TI  - Various strategies to tune the ionic/electronic properties of electrode
      materials.
AB  - This Perspective highlights, through several snapshot examples, the importance of
      electrochemically-driven redox reactions in tuning the electronic/ionic as well
      as magnetic properties of 3d-metal-based inorganic compounds through a careful
      control of the metal oxidation state. Although such redox reactions usually imply
      the electron-ionic duality, they can be extended to insulating compounds
      (LiFePO(4)) or semiconductors (CoO) as long as we can combine electrochemistry at
      the nanoscale to reduce diffusion and migration limitations, and provide the
      compounds with electrons through metallic coating techniques. A thorough
      investigation of the composition-structure-property relationships of the
      Li(x)CoO(2) system, through the assembly of LiCoO(2)/Li electrochemical cells has
      led to the identification of the CoO(2) phase, whose property and stability are
      discussed in terms of cationic-anionic redox competition, thus bearing some
      similarity with the high T(c) cuprate superconductors. Such a d-sp redox
      competition could have structural and electronic consequences. Encouraged by the
      recently reported superconductivity in Na(x)CoO(2);yH(2)O phase, the room
      temperature Li(x)CuO(2) phase diagram was reinvestigated through Li-driven
      electrochemical reactions. A solid solution domain was unravelled but
      superconductivity was not evident. With Cu-based materials such as
      Cu(2.33)V(4)O(11), we have shown the feasibility of a new reversible Li
      electrochemically-driven copper extrusion/insertion process, owing to the
      enhanced copper diffusion within the structure.

PMID- 15452622
TI  - Basic materials physics of transparent conducting oxides.
AB  - Materials displaying the remarkable combination of high electrical conductivity
      and optical transparency already from the basis of many important technological
      applications, including flat panel displays, solar energy capture and other opto
      electronic devices. Here we present the basic materials physics of these
      important materials centred on the nature of the doping process to generate n
      type conductivity in transparent conducting oxides, the associated transition to
      the metallic (conducting) state and the detailed properties of the degenerate
      itinerant electron gas. The aim is to fully understand the origins of the basic
      performance limits of known materials and to set the scene for new or improved
      materials which will breach those limits for new-generation transparent
      conducting materials, either oxides, or beyond oxides.

PMID- 15452623
TI  - Electronic phase separation in transition metal oxide systems.
AB  - Electronic phase separation is increasingly getting recognized as a phenomenon of
      importance in understanding the magnetic and electron transport properties of
      transition metal oxides. The phenomenon dominates the rare-earth manganates of
      the formula Ln(1-x)A(x)MnO(3)(Ln = rare earth and A = alkaline earth) which
      exhibit ferromagnetism and metallicity as well as charge-ordering, depending on
      the composition, size of A-site cations and external factors such as magnetic and
      electric fields. We discuss typical phase separation scenarios in the manganates,
      with particular reference to Pr(1-x)Ca(x)MnO(3)(x= 0.3-0.4), (La(1
      x)Ln(x))(0.7)Ca(0.3)MnO(3)(Ln = Pr, Nd, Gd and Y) and Nd(0.5)Sr(0.5)MnO(3).
      Besides discussing the magnetic and electron transport properties, we discuss
      electric field effects. Rare-earth cobaltates of the type Pr(0.7)Ca(0.3)CoO(3)
      and Gd(0.5)Ba(0.5)CoO(3) also exhibit interesting magnetic and electron transport
      properties which can be understood in terms of phase separation.

PMID- 15452624
TI  - Hydrogen in oxides.
AB  - The paper reviews the history and present understanding of protons in oxides;
      their defect chemistry, thermodynamics, and transport. Focus is put on
      correlations between hydration thermodynamics and other materials properties
      which may help to predict proton uptake and proton conduction in oxides. Also
      effects of defect association and the particular problem of high grain boundary
      resistance in high temperature proton conductors are addressed. In the second
      part, a number of experimental observations attributed to the presence of hydride
      ions under mildly reducing conditions are discussed in relation to the
      unlikelihood that general thermodynamic considerations predict of finding these
      species under such conditions.

PMID- 15452625
TI  - Spin dimer and classical spin analyses of the ordered magnetic structures of
      alkali iron pyrophosphates NaFeP(2)O(7) and LiFeP(2)O(7).
AB  - The magnetic oxides NaFeP(2)O(7) and LiFeP(2)O(7), made up of FeO(6) octahedra
      containing high-spin Fe(3+)(d(5)) ions, undergo a three-dimensional
      antiferromagnetic ordering at low temperatures. The strengths of various Fe-O...O
      Fe super-superexchange interactions of NaFeP(2)O(7) and LiFeP(2)O(7) were
      estimated on the basis of spin dimer analysis to probe the nature of their
      ordered magnetic structures. It is found that the critical factor governing the
      strength of a Fe-O...O-Fe super-superexchange interaction is not the Fe...Fe
      distance but the O...O distance. Using the spin exchange parameters thus
      obtained, the total spin exchange interaction energies were calculated for
      various ordered spin arrangements of NaFeP(2)O(7) and LiFeP(2)O(7) on the basis
      of classical spin analysis to confirm that the observed magnetic structures are
      the magnetic ground states.

PMID- 15452626
TI  - Phase separation in manganites induced by orbital-ordering strains.
AB  - Doped manganite perovskites AMnO(3) exhibit a rich variety of electronic
      properties, resulting from the interplay of charge (Mn(3+)/Mn(4+)), spin (Mn
      magnetic moment) and orbital (Mn(3+) Jahn-Teller distortion) degrees of freedom.
      Magnetisation measurements and ESR spectra have been used to study a series of
      eight AMnO(3) perovskites, in which the A cation sites are occupied by a
      distribution of 70% trivalent lanthanide and 30% divalent Ca, Sr or Ba ions.
      These all have a mean A cation radius of 1.20 Angstrom but different values of
      the cation size variance sigma(2). A change from orbital disorder to order
      (cooperative Jahn-Teller distortions) was previously found in the insulating
      regime at sigma(2) = approximately 0.005 Angstrom(2). This work has shown that co
      existence of the orbitally ordered and disordered phases is found in sigma(2)=
      0.0016-0.0040 Angstrom(2) samples, with a difference of 40 K between their Curie
      temperatures. This is ascribed to competition between orbital ordering and
      microstructural lattice strains. At larger sigma(2) > 0.005 Angstrom(2), the
      orbital ordering strains are dominant and only this phase is observed. This
      intermediate temperature phase segregation is one of many strain-driven
      separation phenomena in manganites.

PMID- 15452627
TI  - The pyrochlore family -- a potential panacea for the frustrated perovskite
      chemist.
AB  - Many known complex oxides of general formula A(2)B(2)X(7) adopt the pyrochlore
      structure, a key structure-type that has been shown to demonstrate a vast range
      of useful physical properties. Areas currently of much interest with respect to
      pyrochlores, include metal-insulator transitions, magnetic frustration/spin ices,
      magnetoresistance, superconductivity, ferroelectrics, O/F ionic conductivity,
      mixed conductivity, pigments and catalysis. We present some recent results on
      three types of pyrochlore materials that show unusual magnetic, optical and
      electronic behaviours associated with subtle structural and compositional
      changes. High-resolution powder neutron diffraction studies of the
      superconducting Cd(2)Re(2)O(7) and the ferroelectric Cd(2)Nb(2)O(7) have been
      undertaken on material cooled below room temperature. Both Cd(2)Re(2)O(7) and
      Cd(2)Nb(2)O(7) exhibit small structure distortions, in each case involving a
      distortion from a cubic unit cell, on cooling below approximately 180 K and
      possible models that can be used to describe the low-temperature structures and
      associated atomic displacements are developed and described in this article. A
      range of materials of the general formula Ca(1-x)Ln(x)TaO(2-x)N(1+x), x= 0.5 and
      x= 1, Ln = La-Yb have been synthesised and shown to adopt pyrochlore and/or
      perovskite structures. The absorption spectra of these materials are discussed in
      terms of their structures and compositions.

PMID- 15452628
TI  - Li(+) ion conductivity in rock salt-structured nickel-doped Li(3)NbO(4).
AB  - Two mechanisms of doping Li(3)NbO(4), which has an ordered, rock salt
      superstructure, have been established. In the "stoichiometric mechanism", the
      overall cation-to-anion ratio is maintained at 1:1 by means of the substitution
      3Li(+) + Nb(5+) --> 4Ni(2+). In the "vacancy mechanism", Li(+) ion vacancies are
      created by means of the substitution 2Li(+) --> Ni(2+). Solid solution ranges
      have been determined for both mechanisms and a partial phase diagram constructed
      for the stoichiometric join. On the vacancy join, the substitution mechanism has
      been confirmed by powder neutron diffraction; associated with lithium vacancy
      creation, a dramatic increase in Li(+) ion conductivity occurs with increasing Ni
      content, reaching a value of 5 x 10(-4) Omega(-1) cm(-1) at 300 degrees C for
      composition x= 0.1 in the formula Li(3-2x)Ni(x)NbO(4). This is the first example
      of high Li(+) ion conductivity in complex oxides with rock salt-related
      structures.

PMID- 15452629
TI  - Solid-state NMR study of the anionic conductor Ca-doped Y(2)Ti(2)O(7).
AB  - Doping the pyrochlore (Y(2)Ti(2)O(7)) with the Ca(2+) has been reported to
      improve the oxygen ionic conductivity. (17)O and (89)Y solid-state NMR has been
      used in work reported here to probe the local environment of the oxygen and
      yttrium sites in these materials. Although the conductivity of these materials is
      only moderate, variable-temperature, one-dimensional (17)O NMR experiments and
      two-dimensional (17)O magnetization exchange spectroscopy show that oxygen-ion
      jumps occur between the oxygen sites nearby titanium. Motion at ambient
      temperatures involves the O1 and local environments created by the Ca(2+) doping;
      motion does not involve the O2 oxygen site coordinated to four yttrium ions.

PMID- 15452630
TI  - Structure and inter-phase stability in solvent-free low-dimensional polymer
      electrolytes with high lithium conductivity.
AB  - Two Williamson procedures for the synthesis of the amphiphilic polymers
      poly[2,5,8,11,14-pentaoxapentadecamethylene(5-alkyloxy-1,3-phenylene)]I(abbrev.
      CmO5) are compared. Method X gives polyether-esters; method Y gives pure
      polyethers. In both, a dehydration reaction gives rise to CmO5-CmO1 copolymers.
      Two-phase systems of I with polyoxytetramethylene and polyoxytrimethylene
      copolymers (II) and LiBF(4) have been prepared with and without an interfacial
      stabiliser copolymer III. Highest and most stable conductivities (>5 x 10(-4) S
      cm(-1) at ambient) with low temperature dependence were observed with III, but I
      from method Y showed a tendency to phase separate at ambient.

PMID- 15452631
TI  - Doping and defect association in AZrO(3) (A = Ca, Ba) and LaMO(3) (M = Sc, Ga)
      perovskite-type ionic conductors.
AB  - Computer simulation techniques have been used to investigate the defect chemistry
      of perovskite-structured ionic conductors based upon AZrO(3)(A = Ca, Ba) and
      LaMO(3)(M = Sc, Ga). Our studies have examined dopant site-selectivity, oxide ion
      migration and dopant-defect association at the atomic level. The energetics of
      dopant incorporation in AZrO(3) show strong correlation with ion size. We predict
      Y(3+) to be one of the most favourable dopants for BaZrO(3) on energetic grounds,
      which accords with experimental work where this cation is the commonly used
      acceptor dopant for effective proton conduction. Binding energies for hydroxy
      dopant pairs in BaZrO(3) are predicted to be favourable with the magnitude of the
      association increasing along the series Y < Yb < In < Sc. This suggests that
      proton mobility would be very sensitive to the type of acceptor dopant ion
      particularly at higher dopant levels. Oxygen vacancy migration in LaScO(3) is via
      a curved pathway around the edge of the ScO(6) octahedron. Dopant-vacancy
      clusters comprised of divalent dopants (Sr, Ca) at the La site have significant
      binding energies in LaScO(3), but very low energies in LaGaO(3). This points to
      greater trapping of the oxygen vacancies in doped LaScO(3), perhaps leading to
      higher activation energies at increasing dopant levels in accord with the
      available conductivity data.

PMID- 15452632
TI  - What variable-pressure variable-temperature measurements are telling us about ion
      transport in glass.
AB  - Variable-pressure, variable-temperature (VPVT) measurements of ionic conductivity
      in typical inorganic (sodium aluminoborate and lithium-sodium phosphate) glasses
      provide information concerning two independent activation parameters: the
      activation energy (E(A) = - R d ln sigma T/d(1/T)) and the activation volume
      (V(A) = - RT d ln sigma/dP). In single-cation glasses there is no simple link
      between E(A) and V(A). The strong increase in E(A) seen with decreasing alkali
      content is not paralleled by an increase in V(A). However, in mixed cation
      glasses, maxima are observed in both E(A) and V(A). To account for these
      observations, a new model is being developed where ion transport is limited by a
      shortage of available volume. In this model, the measured V(A) values represent
      the volumes of opened up 'target sites', the larger values observed in mixed
      cation glasses providing evidence for the coupled motion of unlike ions. The
      extent of this pairwise coupling increases with increasing temperature.

PMID- 15452633
TI  - Simulating surface diffusion and surface growth in ceramics.
AB  - We examine the movement of ion pairs on the surfaces of simple oxides. Using
      temperature-accelerated dynamics the elementary processes involved are identified
      and the activation energies of these used as input to kinetic Monte Carlo
      simulations. Results are presented for the motion of BaO and SrO ion pairs on the
      (100) surfaces of BaO and SrO, respectively, and the formation of island pairs on
      these surfaces is studied. The simulations reveal the importance of exchange
      mechanisms in surface diffusion and growth of oxides. The importance of such
      reactions has been recognised previously for metallic surfaces but not for ionic
      systems, where it has been assumed that ionic surface diffusion is surface
      diffusion via the hopping motion of ion pairs from one surface site to another.
      Exchange mechanisms can dominate transport processes both on terraces and steps
      for both homoepitaxial and heteroepitaxial growth. We suggest the unavoidable
      mixing when an exchange mechanism operates must be considered when attempting to
      grow sharp interfaces in oxide nanostructures.

PMID- 15452634
TI  - The interdependence of defects, electronic structure and surface chemistry.
AB  - In this article we present three diverse applications of first-principles
      simulations to problems of materials chemistry and chemical physics. Their common
      characteristic is that they are essentially problems of the relationships among
      atomic structures and the properties they promote in real materials and real
      applications. The studies are on transition-metal oxide surface chemistry, the
      reactivity and electronic structure of sp(2)-bonded carbon systems, and defects
      and electrochromic properties in WO(3). In these demanding applications we must
      have concern for how realistic our model systems are and how well current
      implementations of DFT perform, and we comment on both.

PMID- 15452635
TI  - Phosphorus carbides: theory and experiment.
AB  - The recent finding that radio frequency plasma activation of CH(4)/PH(3) gas
      mixtures can yield films with P : C ratios < or = 3 has served to trigger further
      research into new 'phosphorus carbide' materials. Theoretical and experimental
      results relating to periodic and amorphous materials, respectively, are presented
      here: (i) The electronic structure and stability of different crystalline
      phosphorus carbide P(x)C(y) phases have been studied using first-principles
      density-functional theory. Calculations have been carried out for P(4)C(3+8 n)
      (n= 0-4), PC, and PC(3) and the most likely periodic structures examined in
      detail. Particular attention is paid to the composition PC(3), for which there
      are several possibilities of similar energy. (ii) Recent experimental efforts
      have involved use of pulsed laser ablation methods to produce hydrogen-free
      phosphorus carbide thin films. Mechanically hard, electrically conducting diamond
      like carbon films containing 0- approximately 26 at.% P have been deposited on
      both Si and quartz substrates by 193 nm PLA of graphite/phosphorus targets
      (containing varying percentages of phosphorus), at a range of substrate
      temperatures (T(sub)= 298-700 K), in vacuum, and analysed via laser Raman and X
      ray photoelectron spectroscopy.

PMID- 15452636
TI  - Evolution of structure, transport properties and magnetism in ternary lithium
      nitridometalates Li(3-x-y)M(x)N, M = Co, Ni, Cu.
AB  - The structures, magnetism and ion transport properties of the ternary nitrides
      Li(3-x-y)M(x)N (M = Co, Ni, Cu; y= lithium vacancy) were examined by powder X-ray
      diffraction, solid-state NMR and SQUID magnetometry. Doping levels are achieved
      up to x approximately = 0.4 for M = Cu and Co, but much higher substitution
      levels (x approximately =1) are obtained in the Li-Ni-N system. Transition metals
      substitute for Li at the Li(1) interplanar site and the ensuing lithium vacancies
      are disordered within the [Li(2)N] planes. High substitution levels in the Li-Ni
      N system lead to the formation of ordered phases. Diffusion parameters, including
      activation energies, correlation times and diffusion coefficients, were obtained
      from variable-temperature solid-state NMR measurements in several ternary
      compounds. SQUID magnetometry shows significant variations of the electronic
      properties with dopant and x. The properties of the ternary nitrides can be
      rationalised in terms of the identity of the dopant and the structural
      modifications arising from the substitution process.

PMID- 15452637
TI  - Computer modelling of mixed metal fluorides for optical applications.
AB  - This paper describes a new computational method for predicting the optical
      behaviour of doped inorganic materials. There is considerable interest in using
      inorganic materials in photonic devices, and in many cases, the optical
      properties of these materials depend on doping by ions such as those from the
      rare earth series. Among the inorganic materials of interest are the mixed metal
      fluorides (e.g. BaLiF(3), BaY(2)F(8), YLiF(4), LiCaAlF(6), LiSrAlF(6)), doped
      with trivalent rare earth ions. The paper describes the use of Mott-Littleton
      calculations to determine the optimum location for dopant ions, followed by
      crystal field calculations which make direct use of the output of the Mott
      Littleton calculations to calculate the optical properties of the dopant ion
      taking into account its symmetry and the positions of the surrounding ions,
      including any vacancies or interstitial ions present by virtue of charge
      compensation. It is then possible to predict whether a given dopant ion at a
      particular site in a material will have favourable optical properties.

PMID- 15452638
TI  - Oxide ion diffusion in optimised LAMOX materials.
AB  - A series of optimised materials in the family with parent compound La(2)Mo(2)O(9)
      have been studied using the isotope exchange depth profile technique and SIMS
      analysis. The data collected indicate that the oxide ion diffusion coefficients
      in both the parent compound and optimised materials are significantly higher than
      those reported for any of the fluorite structured electrolyte materials, with a
      peak value for the La(1.7)Gd(0.3)Mo(2)O(9) composition of 1.41 x 10(-6) cm(2) s(
      1) at 800 degrees C. Further, it was found that the substitution of isotopic
      oxygen into the ceramic was limited in dry atmospheres but significantly enhanced
      in a H(2)(18)O/(16)O atmosphere, in common with recent reports on the
      diffusion/exchange behaviour of the BIMEVOX class of oxide ion conductors.

PMID- 15452639
TI  - Doping strategies to optimise the oxide ion conductivity in apatite-type ionic
      conductors.
AB  - The apatite-type phases, La(9.33+x)(Si/Ge)(6)O(26+3x/2), have recently been
      attracting considerable interest as potential electrolytes for solid oxide fuel
      cells. In this paper we report results from a range of doping studies in the Si
      based systems, aimed at determining the key features required for the
      optimisation of the conductivities. Systems examined have included alkaline earth
      doping on the rare earth site, and P, B, Ga, V doping on the Si site. By suitable
      doping strategies, factors such as the level of cation vacancies and oxygen
      excess have been investigated. The results show that the oxide ion conductivities
      of these apatite systems are maximised by the incorporation of either oxygen
      excess or cation vacancies, with the former producing the best oxide ion
      conductors. In terms of samples containing cation vacancies, conductivities are
      enhanced by doping lower valent ions, Ga, B, on the Si site. The presence of
      higher valent ions on these sites, e.g. P, appears to inhibit the incorporation
      of excess oxygen within the channels, and so limits the maximum conductivity that
      can be obtained. Overall the results suggest that the tetrahedral sites play a
      key role in the conduction properties of these materials, supporting recent
      modelling studies, which have suggested that these tetrahedra aid in the motion
      of the oxide ions down the conduction channels by co-operative displacements.

PMID- 15452640
TI  - Influence of synthesis route on the properties of doped lanthanum cobaltite and
      its performance as an electrochemical reactor for the partial oxidation of
      natural gas.
AB  - La(0.6)Sr(0.4)Co(0.2)Fe(0.8)O(3-delta)(LSCF) perovskite powders have been
      synthesised by solid-state reaction, co-precipitation, drip pyrolysis and citrate
      gel routes, and characterised using XRF, XRD, SEM and BET. Co-precipitation using
      oxalic acid or aqueous ammonia as precipitant failed to achieve the correct
      chemical composition. Perovskite structures were achieved in all other cases.
      Surface areas ranging from 0.6 to 17.4 m(2) g(-1) were obtained, which was
      reflected in the different microstructures observed. The citrate gel product
      exhibited a convoluted network morphology resulting in its large surface area.
      Thin-walled (approximately 200 microm) tubular membranes have been manufactured
      from the LSCF powders using viscous plastic processing. The tubes have been
      characterised using a custom-built gas analysis rig with on-line mass
      spectrometry. Porosity levels of the membranes were found to be very low (<0.1%).
      The spontaneous oxygen flux across the tubular membranes was determined as a
      function of temperature. Oxygen permeation rates ranged from 0.1 to 0.3 micromol
      cm(-2) s(-1) at 1273 K. The catalytic behaviour of the LSCF tubes towards methane
      oxidation has been studied using temperature programmed reaction and conventional
      catalytic measurements. The tubes favoured combustion reactions, with smaller
      amounts of partial oxidation and oxidative coupling products observed. Powder
      coatings have been incorporated to establish the effect of increasing surface
      area.

PMID- 15452641
TI  - Structure and reactivity of V(2)O(5): bulk solid, nanosized clusters, species
      supported on silica and alumina, cluster cations and anions.
AB  - Vanadyl bond dissociation energies are calculated by density functional theory
      (DFT). While the hybrid (B3LYP) functional results are close to the available
      reference data, gradient corrected functionals (BP86, PBE) yield large errors
      (about 50 to 100 kJ mol(-1)), but reproduce trends correctly. PBE calculations on
      a V(20)O(62)H(24) cluster model for the (001) surface of V(2)O(5) crystals
      virtually reproduce periodic slab calculations. The low bond dissociation energy
      (formation of oxygen surface defect) of 113 kJ mol(-1)(B3LYP) is due to
      substantial structure relaxations leading to formation of V-O-V bonds between the
      V(2)O(5) layers of the crystal. This relaxation cannot occur in polyhedral
      (V(2)O(5))(n) clusters and also not for V(2)O(5) species supported on silica or
      alumina (represented by cage-type models) for which bond dissociation energies of
      250-300 kJ mol(-1) are calculated. The OV(OCH(3))(3) molecule and its dimer are
      also considered. Radical cations V(2)O(5)(+) and V(4)O(10)(+) have very low bond
      dissociation energies (22 and 14 kJ mol(-1), respectively), while the
      corresponding radical anions have higher dissociation energies (about 330 kJ mol(
      1)) than the neutral clusters. The bond dissociation energies of the closed shell
      V(3)O(7)(+) cation (165 kJ mol(-1)) and the closed shell V(3)O(8)(-) anion (283
      kJ mol(-1)) are closest to the values of the neutral clusters. This makes them
      suitable for gas phase studies which aim at comparisons with V(2)O(5) species on
      supporting oxides.

PMID- 15452642
TI  - Rubidium doped zeolite rho: structure and microwave conductivity of a metallic
      zeolite.
AB  - Large crystallites of high purity zeolite rho were synthesized by controlled
      monitoring of the aging and heating period of the mother gel. The microwave
      conductivity of Rb-rho doped with up to 20 Rb atoms per unit cell was measured
      over the temperature range 15-300 K, and the structures of three of the samples
      were examined through Rietveld analysis of powder neutron diffraction data. At
      low concentrations of rubidium dopant the observed microwave responses were
      dominated by polarization effects. In the sample Rb(17)/Rb-rho a strongly
      temperature-dependent electronic contribution to the conductivity was observed
      above approximately =150 K. In Rb(20)/Rb-rho, conductivities in the range 1.5-2.3
      Sm(-1) were observed between 15 and 300 K. This residual conductivity at 15 K,
      unprecedented in a zeolite, indicates that the sample is indeed metallic;
      however, the values of conductivity measured are low in comparison to
      conventional metals and comparable to those of doped semiconductors. The
      evolution of the conducting behaviour is discussed in relation both to observed
      structural and to possible electronic changes occurring within the samples on
      metal doping.

PMID- 15452643
TI  - Structural and electrical characterisation of Li(2)O : TiO(2) : SnO(2) : P(2)O(5)
      electrolyte glass.
AB  - Glasses of general formula 50Li(2)O : xSnO(2) : (10 -x)TiO(2) : 40P(2)O(5)(0.0 <
      or = x < or = 10) were investigated by differential scanning calorimetry, X-ray
      diffraction and ac impedance, (31)P solid-state NMR and IR spectroscopies. Three
      isotropic resonances can be identified in the (31)P NMR spectra, which have been
      assigned to various phosphate species. Analysis of the ratios of integrated
      intensities in the (31)P spectra leads to models for the Ti and Sn coordination
      environments. Both TiO(2) and SnO(2) are found to be predominantly network
      forming with Ti and Sn proposed to be in five- and four-coordinate environments
      respectively. Analysis of ac impedance spectra collected at low temperatures
      reveals two forms of permittivity dispersion, viz: high frequency conductivity
      dispersion and Cole-Cole type relaxation of permittivity. The activation energy
      of the relaxation frequency of the permittivity dispersion is equal to that of
      the dc conductivity, which is consistent with cooperative motion of lithium ions.
      The results also suggest that the observed increase in conductivity with
      temperature appears to be mainly due to an increase in mobility rather than
      increase in carrier concentration.

PMID- 15452644
TI  - Expanded fullerides and electron localisation -- lithium-rich ammoniated C(60)
      phases.
AB  - The synthesis and characterisation of alkali metal fullerides with complex
      counterions consisting of ammonia ligands coordinated to lithium cations is
      discussed. The body-centred cubic packing and accompanying low density of
      fulleride anions produces localisation of the t(1u) outer electrons of the
      fulleride anions. This is demonstrated by the electronic behaviour of the x = 3
      and 5 members of the series, the latter representing the first detailed study of
      the electronic behaviour of a localised electron fulleride with five electrons
      per anion.

PMID- 15452645
TI  - Lattice collapse in mixed-valence samarium fulleride Sm(2.75)C(60) at high
      pressure.
AB  - Sm(2.75)C(60) displays large negative thermal expansion behaviour in the
      temperature range 4.2-32 K at ambient pressure as a result of a quasi-continuous
      valence change from the larger Sm(2+) towards the smaller Sm(2.3+) ion. Here we
      use the powder synchrotron X-ray diffraction technique at ambient temperature and
      elevated pressures to study the compression behaviour in the pressure range 0-6
      GPa. An abrupt hysteretic phase transition, accompanied by a dramatic volume
      decrease (approximately =6.0%) and a change in colour from black to golden was
      found at approximately =4 GPa induced by a sudden Sm valence transition from +2.3
      towards +3. Such behaviour is typical of highly correlated Kondo insulators like
      SmS and makes Sm(2.75)C(60) the first known molecular-based member of this
      fascinating class of materials.

PMID- 15452646
TI  - Transport numbers from hydrogen concentration cells over different oxides under
      oxidising and reducing conditions.
AB  - Partial hydrogen ion conductivity in acceptor doped CaTiO(3), BaCeO(3) and ZrO(2)
      and nominally undoped BaTiO(3) and TiO(2) has been investigated by transport
      number measurements using the hydrogen concentration cell/EMF method in wet
      atmospheres as a function of pO(2)(10(-20)-1 atm) at 800 or 1000 [degree]C. All
      oxides investigated, except ZrO(2), show minor proton conductivity in oxidising
      atmospheres. Earlier indications of apparent negative charge transport by
      hydrogen under reducing conditions and high temperatures in SrTiO(3) samples have
      been reproduced for all the investigated oxides including ZrO(2).

PMID- 15452647
TI  - Dalton Discussion No. 7: Ionic and electronic properties of solids.

PMID- 15452648
TI  - Raphanus sativus (Radish): their chemistry and biology.
AB  - Leaves and roots of Raphanus sativus have been used in various parts of the world
      to treat cancer and as antimicrobial and antiviral agents. The phytochemistry and
      pharmacology of this radish is reviewed. The structures of the compounds isolated
      and identified are listed and aspects of their chemistry and pharmacology are
      discussed. The compounds are grouped according to structural classes.

PMID- 15452649
TI  - Management of nitrogen through the use of leaf color chart (LCC) and soil plant
      analysis development (SPAD) or chlorophyll meter in rice under irrigated
      ecosystem.
AB  - A field experiment was conducted in a farmer"s field in the district of Nadia,
      West Bengal, India to study the management of N through leaf color chart (LCC)
      and soil plant analysis development (SPAD) or chlorophyll meter in rice (cv. IET
      4094) during the Kharif (wet season) of 2001-2002 and 2002-2003 by taking the
      treatment combinations based on different levels of N at fixed schedule and
      through LCC and SPAD. The experimental soil (0-15 cm) had pH 7.33; organic C
      0.43%; available N 408.70 kg ha(-1); available P 6.92 kg ha(-1); and available K
      66.31 kg ha(-1). The results of LCC and SPAD or chlorophyll meter for the N
      management in rice show that values of both LCC and SPAD significantly increased
      with an increasing level of N. The mean values of LCC and SPAD varied from 3.19
      5.31 and 27.36-39.26, respectively, in rice. The results show that the amount of
      N can be saved as 20-42.5 and 27.5-47.5 kg N ha(-1) through the use of LCC and
      SPAD in rice over the fixed-timing N treatment T7 where 150 kg N ha(-1) was
      applied in three (3) splits without reduction in the yield. The SPAD- and LCC
      treated N plot showed higher N-use efficiency over fixed-scheduling N treatment
      in rice. The results further show that SPAD value of 37 and LCC value of 5 have
      been proved to be superior treatments over SPAD (35) and LCC (4) for the best
      management of N in rice in an Inceptisol.

PMID- 15452650
TI  - Diastematomyelia: a case with familial aggregation of neural tube defects.
AB  - Intrauterine neural tube defects, meningomyelocele, and diastematomyelia are
      developmental errors at different stages of the closure of the neural tube. The
      familial aggregation of these neural tube defects is not previously reported in
      the literature and should make one think about a common embryogenesis and a
      possible common mechanism of etiopathogenesis leading to anomalies at different
      stages of this embryogenesis. This paper presents a 12-year-old Turkish boy with
      diastematomyelia who was suspected with a demonstrative dermatologic finding
      without any neurologic sign and diagnosed with magnetic resonance imaging (MRI).
      He has a positive family history of a stillbirth with neural tube defect, an
      exitus with meningomyelocele, and an epileptic child in his female siblings.

PMID- 15452651
TI  - [Shock trauma room management of pelvic injuries. A systematic review of the
      literature].
AB  - OBJECTIVE: Injuries to the pelvis may occur as a life threatening situation which
      then requires immediate surgical treatment. A review of the literature represents
      the range of current recommendations. METHODS: Clinical trials were
      systematically collected (Medline, Cochrane and hand searches) reviewed and
      classified into evidence levels (1 to 5 according to the Oxford system). RESULTS:
      According to the literature there is a consent that immediate resuscitation and
      surgical intervention is essential in complex pelvic fractures. In contrast the
      way of emergency stabilization of the pelvis (fixateur externe or c-clamp) is
      still under discussion as well as the radiological diagnostic (x-ray or CT) and
      the way of bleeding control (tamponade or embolization). CONCLUSION: Emergency
      management of pelvic fractures means treatment of a life threatening injury in
      first place. Although there are different methods that can be used, they all
      follow the same principle of resuscitation and mechanical stabilization of the
      pelvis in parallel.

PMID- 15452652
TI  - [Diagnosis and immediate therapeutic management of limb injuries. A systematic
      review of the literature].
AB  - OBJECTIVE: Limb injuries are often underestimated in the diagnostic procedures
      initiated in the resuscitation room. Missed diagnosis is therefore a frequent
      consequence in this issue. A systematic analysis of evidence-based procedures was
      therefore investigated in this paper. METHODS: Clinical trials were
      systematically collected (Medline, Cochrane and hand searches) and classified
      into evidence levels (1 to 5 according to the Oxford system). RESULTS: Following
      admission of a multiple trauma patient vital functions have to be established in
      first priority. After stabilization a systematic clinical investigation and
      consecutive specific radiological procedures should rule out extremity injuries.
      These are the only evidence-based criteria leading to a complete detection of all
      limb injuries. All other aspects are only based on clinical experience or the
      opinion of expert committees. CONCLUSION: The quality of shock room management is
      mostly dependent on the experience of the " trauma team" (and especially of the
      trauma leader). Guidelines and specific trauma algorithms can provide a helpful
      instrument in this issue.

PMID- 15452653
TI  - [Principles of callus distraction].
AB  - Callus distraction is based on the principle of regenerating bone by continuous
      distraction of proliferating callus tissue. It has become the standard treatment
      of significant leg shortening and large bone defects. Due to many problems and
      complications, exact preoperative planning, operative technique and careful
      postoperative follow-up are essential. External fixators can be used for all
      indications of callus distraction. However, due to pin tract infections, pain and
      loss of mobility caused by soft tissue transfixation, fixators are applied in
      patients with open growth plates, simultaneous lengthening with continuous
      deformity corrections, and increased risk of infection. Distraction over an
      intramedullary nail allows removal of the external fixator at the end of
      distraction before callus consolidation (monorail method). The intramedullary
      nail protects newly formed callus tissue and reduces the risk of axial deviation
      and refractures. Recently developed, fully intramedullary lengthening devices
      eliminate fixator-associated complications and accelerate return to normal daily
      activities. This review describes principles of callus distraction, potential
      complications and their management.

PMID- 15452654
TI  - [Priority-oriented shock trauma room management with the integration of multiple
      view spiral computed tomography].
AB  - In major trauma it is essential to immediately recognize and treat life
      threatening problems and conditions. Most trauma protocols reserve the use of
      computed tomography for the secondary survey, as patients cannot be attended to
      during the examination and must be transferred from the emergency room to the CT
      suite. The relevant reduction in the scanning time of multidetector computed
      tomography (MDCT) or multislice computed tomography (MSCT) justifies its use as
      the major diagnostic adjunct for primary trauma survey and initial resuscitation.
      According to our ATLS((R))-based trauma algorithm, the multidetector scanner
      situated in the emergency department is utilized immediately after the correction
      of respiratory problems to detect causes of bleeding or intracranial hematomas.
      In a prospective series a total of 125 consecutive major trauma patients were
      evaluated. After focused sonography in trauma (FAST) and plain chest films in
      intubated patients, whole body MDCT was performed. By retrieving data from our
      trauma registry and a picture archiving and communication system (PACS), time
      from trauma room admission to the end of head CT scan for the entire MDCT study
      and calculation of multiplanar reconstruction (MPR) was analyzed. Additionally,
      relevant complications such as untreated tension pneumothorax or circulatory
      arrest during MDCT examination were recorded. The time from admission to the
      trauma room until completion of head CT scan without contrast was 21:12 min
      (median, IQR 18:13-27:52). The entire contrast-enhanced MDCT study, including
      pilot scan and contrast application, required 6:08 min (median, IQR 4:33-8:14)
      with a total scanning time of 0:59 min (median, IQR 0:55-1:03). MPR calculation
      of the spine and bony pelvis was performed in 11:37 min (median, IQR 8:03-16:41).
      A relevant life-threatening complication due to CT scanning during primary trauma
      survey was not observed in the 125 cases (0/125 CI 95% 0%-3%). Complete
      diagnostic imaging can be performed within 30 min after trauma room admission by
      using MDCT. During the primary survey, treatment of the patient is interrupted
      just for the few minutes of the CT scan and contrast application. An adequate
      survey of injuries can be achieved earlier and a targeted therapy can be
      initiated ahead of time. Integration of MDCT scanners in the primary trauma
      survey provides a high standard of imaging in a very short time without
      endangering the patient. When dealing with multiple casualties, MDCT could be
      used also as an accurate and time-efficient means of hospital triage to diagnose
      and prioritize patients and to plan further surgical interventions and intensive
      care.

PMID- 15452655
TI  - [The importance of Advanced Trauma Life Support (ATLS) in the emergency room].
AB  - INTRODUCTION: There is clinical evidence, that a standardized management of
      trauma patients in the emergency room improves outcome. METHODS: The ATLS
      training course teaches a systematic approach to the trauma patient in the
      emergency room. The aim is a rapid and accurate assessment of the patient's
      physiologic status, the treatment according to priorities and the decision making
      if transfer to a trauma center is necessary. The German Trauma Society has taken
      over the course concept from the American College of Surgeons (ACS) and is
      authorized to organize ATLS courses in Germany. RESULTS: A standardized
      management in the emergency room helps to prevent secondary injury, to realize
      timing as a relevant factor in the initial treatment and to assure a high
      standard of care. The ATLS course provides the participant with knowledge, skills
      and attitudes and is open to doctors of all specialties involved in the initial
      management of severely injured patients. CONCLUSION: ATLS teaches a standardized
      and established approach to the trauma patient in the emergency room. It has been
      transferred to 46 countries and the content is reviewed regularly to consider new
      scientific evidence. Germany has the chance to participate in this international
      standard of care and to introduce own experiences into the review process.

PMID- 15452657
TI  - [A rapid review of the minimum quality problems using total knee arthroplasty as
      an example. Where do the magical threshold values come from?].
AB  - We set out to clarify whether in hospitals with a large volume morbidity and
      mortality rates after total knee arthroplasty (TKA) can be improved, whether the
      effects are consistent, and whether minimum recommendable caseloads can be
      inferred. We conducted a systematic review using MEDLINE, EMBASE, CENTRAL, and
      CINAHL and performed a hand search without restrictions on language or
      publication types. We identified 1406 citations, of which 13 studies including
      1,110,962 patients met our inclusion criteria. Of these, six studies explored the
      same administrative data source. Five studies enrolling 448,897 were eligible for
      quantitative analysis. All studies corresponded to evidence level 2b (prospective
      or retrospective cohort study with >80% follow-up). We found homogeneous results
      about hospital mortality. Between 2551 and 821 TKA must be performed by high
      volume rather than by low-volume providers to prevent 1 extra death. Absolute
      event rates are notably small.

PMID- 15452656
TI  - [Decision making and and priorities for surgical treatment during and after shock
      trauma room treatment].
AB  - OBJECTIVE: Concepts for optimal surgical treatment of the patient with blunt
      multiple injuries are being evaluated on the basis of the current literature.
      METHODS: Clinical trials were systematically collected (Medline, Cochrane and
      hand searches) and classified into evidence levels (1 to 5 according to the
      Oxford system). RESULTS: The posttraumatic clinical course is divided into four
      different periods: acute-, primary-, secondary- und tertiary period. The first
      and second period are important for life saving surgery and the stabilization of
      major fractures. After the cardiorespiratory systems have been stabilized, the
      following priorities have been formulated: head, face, spine, abdomen,
      extremities. To restrict the degree of operative burden on the patient it appears
      to be necessary to limit the duration of initial surgery to less than 6 hours. In
      patients at high risk to develop posttraumatic complications-"borderline
      patients"-it appears safer to perform only temporary fixation of major fractures.
      CONCLUSIONS: Three different factors determine the clinical course after
      polytrauma: Trauma represents the first hit, followed by the therapy-induced
      burden (second hit). In addition, the third hit is represented by the individual
      response. An evaluation of the clinical status by immunologic monitoring can be
      performed in order to assess the patient's status.

PMID- 15452658
TI  - [Evidence of shock trauma room care].

PMID- 15452659
TI  - [Deficiencies in the practical management of certain emergency situations.
      Improvement in the emergency medical qualifications through practice oriented
      course concepts].

PMID- 15452660
TI  - Neuronal control of turtle hindlimb motor rhythms.
AB  - The turtle, Trachemys scripta elegans, uses its hindlimb during the rhythmic
      motor behaviors of walking, swimming, and scratching. For some tasks, one or more
      motor strategies or forms may be produced, e.g., forward swimming or
      backpaddling. This review discusses experiments that reveal characteristics of
      the spinal neuronal networks producing these motor behaviors. Limb-movement
      studies show shared properties such as rhythmic alternation between hip flexion
      and hip extension, as well as variable properties such as the timing of knee
      extension in the cycle of hip movements. Motor-pattern studies show shared
      properties such as rhythmic alternation between hip flexor and hip extensor motor
      activities, as well as variable properties such as modifiable timing of knee
      extensor motor activity in the cycle of hip motor activity. Motor patterns also
      display variations such as the hip-extensor deletion of rostral scratching.
      Neuronal-network studies reveal mechanisms responsible for movement and motor
      pattern properties. Some interneurons in the spinal cord have shared activities,
      e.g., each unit is active during more than one behavior, and have distinct
      characteristics, e.g., each unit is most excited during a specific behavior.
      Interneuronal recordings during variations support the concept of modular
      organization of central pattern generators in the spinal cord.

PMID- 15452661
TI  - Scattered micronodular high density lung opacities due to mercury embolism.

PMID- 15452662
TI  - Use of ultrasound in the detection of intestinal drug smuggling.

PMID- 15452664
TI  - Visual estimation of the global myocardial extent of hyperenhancement on delayed
      contrast-enhanced MRI.
AB  - MRI with paramagnetic contrast agent allows the assessment of the extent of
      myocardial tissue injury after infarction. Visual segmental scoring has been
      widely used to define the transmural extent of myocardial infarction, but no
      attempt has been made to use visual scores in order to assess the percentage of
      the whole myocardium infarcted. By summing all the segmental scores using a 17
      segment model, a global index of the size of the infarcted myocardium is easily
      obtained. The entire left ventricle of 60 patients with a recent myocardial
      infarction was scanned using an ECG-gated gradient echo sequence after injection
      of gadolinium contrast agent. The global score was defined as the sum of the
      scores on each segment, and expressed as a percentage of the maximum possible
      score. This index was compared with a planimetric evaluation of hyperenhancement,
      expressed as a percentage of the left ventricle myocardial volume. There is a
      good correlation between the two methods (r=0.91; y=1.06x+0.20), and the Bland
      Altman plot shows a high concordance between the two approaches (mean of the
      differences =1.45%). A visual approach based on a 17-segment model can be used to
      evaluate the global myocardial extent of the hyperenhancement with similar
      results to planimetry.

PMID- 15452665
TI  - Detection, visualization and evaluation of anomalous coronary anatomy on 16-slice
      multidetector-row CT.
AB  - Early identification and evaluation of relatively frequent anomalous coronary
      anatomy is quite relevant because of the occurrence of sudden cardiac death or
      related symptoms of myocardial ischemia. Selective coronary angiography (CAG) is
      invasive, expensive and cannot always provide the required information
      adequately. Recently, non-invasive imaging techniques such as magnetic resonance
      imaging and multidetector-row computed tomography (MDCT) have been shown to
      provide a good anatomical view of the coronary artery tree. This study aims to
      demonstrate the value of 16-MDCT for evaluation of anomalous coronary anatomy. In
      13 patients scanned using 16-MDCT, six different coronary anomalies were
      diagnosed [two absent left main, one single vessel left coronary artery (LCA),
      three LCA originating from the right (two with interarterial course), six right
      coronary artery originating from the left, one double left anterior descending
      (LAD)]. Mean diagnostic quality, recorded by two observers using a 5-point scale
      (1= non-diagnostic to 5= excellent diagnostic quality), resulted in a mean score
      of 3.73 (SD 1.19) without any non-diagnostic result. MDCT offers an accurate
      diagnostic modality to visualize the origin and course of anomalous coronary
      arteries by a three-dimensional display of anatomy. Shortcomings in CAG can be
      overcome by the use of contrast-enhanced MDCT.

PMID- 15452666
TI  - Allogeneic stem cell transplantation for the treatment of lysosomal and
      peroxisomal metabolic diseases.
AB  - This is a review of the clinical responses and prospectus of new therapies
      following use of allogeneic hematopoietic stem cell transplantation for the
      treatment of the following disorders: Hurlers syndrome (MPS 1-H), globoid cell
      leukodystrophy (GLD; Krabbes disease), adrenoleukodystrophy, metachromatic
      leukodystrophy, Wolmans disease, I-cell disease (mucolipidosis II; MLS-II), alpha
      mannosidosis, fucosidosis, Niemann-Pick B/A disease, Slys disease (MPS VII),
      Gauchers disease (Gaucher-II-III), Battens disease, Farbers disease, Sanfilippo
      syndrome (MPS-III), Hunters disease (MPS-II), Maroteaux-Lamy syndrome (MPS-VI),
      and aspartylglucosaminuria (AGU). Over 500 patients with lysosomal and
      peroxisomal metabolic storage diseases due to deficiency of primary enzymes have
      been treated with hematopoietic stem cell transplantation since the initial
      patient was treated a quarter of century ago. Normal enzymatic activity has been
      robust and continuous over these years without the need for any medication. Proof
      of principle has been reported for multiple positive effects including that of
      the reconstruction of the central nervous system. Furthermore, the excellent
      engraftment rate along with significantly diminished graft-vs-host-disease needs
      to be emphasized. The genetic diseases enumerated above have remarkable
      differences from those discussed elsewhere in this issue of Seminars in
      Immunopathology. Each has a greater genetic heterogeneity. Misdiagnosis resulting
      in delay of treatment and further decline of function and ultimate quality of
      life occurs almost all the time. Neonatal screening of these diseases will be
      mandatory to vastly improve outcomes. Plans are being implemented to use dried
      blood spots on filter paper, as is commonly done for many other genetic diseases.
      Many new therapies are being adopted which should enhance positivity and
      acceptance of treatment by hematopoietic stem cell transplantation.

PMID- 15452667
TI  - Staurosporine-induced G2/M arrest in primary effusion lymphoma BCBL-1 cells.
AB  - Staurosporine, an inhibitor of protein kinase C, is a potential antitumor drug
      and its derivatives are used as anticancer drugs in clinical trials. Human
      herpesvirus 8 (HHV-8) is implicated in all forms of Kaposi's sarcoma (KS),
      primary effusion lymphoma (PEL), and multicentric Castleman's disease (MCD),
      indicating it to be a DNA tumor virus. It is difficult to culture cell lines
      derived from KS patients; we therefore used a cell line derived from PEL (BCBL-1)
      to investigate whether staurosporine affects the HHV-8-related tumors. Our
      results show that staurosporine treatment reduces the cell viability of BCBL-1
      cells and causes cell cycle arrest in the G2/M phase. The G2/M arrest was
      associated with the decrease in the expression of Cdc2 and cyclin B. Furthermore,
      the induction of the HHV-8 lytic cycle was not observed under the staurosporine
      treatment.

PMID- 15452668
TI  - Concomitant zoster myelitis and cerebral leukemia relapse after stem cell
      transplantation.

PMID- 15452669
TI  - Enteropathy-associated T-cell lymphoma without a prior diagnosis of coeliac
      disease: diagnostic dilemmas and management options.
AB  - Enteropathy-associated T-cell lymphoma (EATL) ultimately develops in 7-10% of
      patients with long-standing coeliac disease. In patients without a prior
      diagnosis of coeliac disease this is a very rare disorder, and the diagnosis in
      such cases is often difficult and delayed due to the non-specific nature of the
      symptoms and a very low index of clinical suspicion. Standard anti-lymphoma
      therapies have minimal utility in patients with EATL, and their prognosis is
      poor. An added difficulty is the high risk of intestinal perforation especially
      with the commencement of treatment due to the multifocal nature of bowel disease
      and poor underlying nutrition and tissue integrity. To illustrate these problems
      and provide an example of how these issues may be addressed, we report the case
      of a patient with EATL who was completely asymptomatic from unsuspected
      underlying coeliac disease and presented initially with back pain followed by
      bowel obstruction. He was treated with gut rest with total parenteral nutrition
      before commencing an intensive chemotherapy regimen [hyper-CVAD
      (cyclophosphamide, vincristine, doxorubicin, and dexamethasone)] and is currently
      well in ongoing complete remission 34 months later.

PMID- 15452670
TI  - Imaging of unstable atherosclerotic lesions.

PMID- 15452671
TI  - Cardiac metaiodobenzylguanidine activity can predict the long-term efficacy of
      angiotensin-converting enzyme inhibitors and/or beta-adrenoceptor blockers in
      patients with heart failure.
AB  - PURPOSE: Although the benefits of treatment with angiotensin-converting enzyme
      (ACE) inhibitors and beta-blockers are well known, no method has as yet been
      established to predict the efficacy of drug therapy. This study tested whether
      cardiac 123I-metaiodobenzylguanidine (MIBG) activity is of prognostic value and
      can predict the improvement in heart failure patients resulting from treatment
      with ACE inhibitors and/or beta-blockers. METHODS: Following quantification of
      the heart-to-mediastinum ratio (HMR) of MIBG activity, 88 patients with heart
      failure who were treated with ACE inhibitors and/or beta-blockers (treated group)
      and 79 patients with heart failure who were treated conventionally without the
      aforementioned agents, and who served as controls, were followed up for 43 months
      with a primary endpoint of cardiac death. RESULTS: The treated group had a
      significantly lower prevalence of cardiac death and a significantly lower
      mortality at 5 years compared with the control group (15% vs 37% and 21% vs 42%,
      p<0.05, respectively). Multivariate analysis revealed that significant predictors
      were HMR, age, nitrate use and ventricular tachycardia for the treated group, and
      HMR, nitrate use and NYHA class for the control group. The drug treatment
      significantly reduced mortality from 36% to 12% when HMR was 1.53 or more and
      from 53% to 37% when HMR was less than 1.53. The reduction in risk of mortality
      within 5 years in patients without a severe MIBG defect (67%) was twice that in
      patients with such a defect (32%) (p<0.05). CONCLUSION: The reduction in
      mortality risk achieved by using ACE inhibitors and/or beta-blockers is
      associated with the severity of impairment of cardiac MIBG uptake. Cardiac MIBG
      activity can consequently be of long-term prognostic value in predicting the
      effectiveness of such treatment in patients with heart failure.

PMID- 15452672
TI  - What is the source of the skeletal affinity of 99mTc-V-DMSA?

PMID- 15452673
TI  - A new method to determine the structure of the metal environment in
      metalloproteins: investigation of the prion protein octapeptide repeat Cu(2+)
      complex.
AB  - Since high-intensity synchrotron radiation is available, "extended X-ray
      absorption fine structure" spectroscopy (EXAFS) is used for detailed structural
      analysis of metal ion environments in proteins. However, the information acquired
      is often insufficient to obtain an unambiguous picture. ENDOR spectroscopy allows
      the determination of hydrogen positions around a metal ion. However, again the
      structural information is limited. In the present study, a method is proposed
      which combines computations with spectroscopic data from EXAFS, EPR, electron
      nuclear double resonance (ENDOR) and electron spin echo envelope modulation
      (ESEEM). From EXAFS a first picture of the nearest coordination shell is derived
      which has to be compatible with EPR data. Computations are used to select
      sterically possible structures, from which in turn structures with correct H and
      N positions are selected by ENDOR and ESEEM measurements. Finally, EXAFS spectra
      are re-calculated and compared with the experimental data. This procedure was
      successfully applied for structure determination of the Cu(2+) complex of the
      octapeptide repeat of the human prion protein. The structure of this octarepeat
      complex is rather similar to a pentapeptide complex which was determined by X-ray
      structure analysis. However, the tryptophan residue has a different orientation:
      the axial water is on the other side of the Cu.

PMID- 15452674
TI  - An in situ hybridization and immunofluorescence study of GABA(A) and GABA(B)
      receptors in the vestibular nuclei of the intact and unilaterally
      labyrinthectomized rat.
AB  - We investigated whether the production of the sixteen subunits of the GABA(A)
      receptors and of the different variants of GABA Breceptors are modulated in rat
      medial vestibular nuclei (MVN) following unilateral labyrinthectomy. Specific
      alpha1-6, beta1-3, gamma1-3 and delta GABA(A) and GABA(B) B1 and B2receptor
      radioactive oligonucleotides were used for in situ hybridization to probe
      sections of rat vestibular nuclei. Specific antibodies against alpha1, beta2,
      beta3 and gamma2 subunits of GABA(A) receptors and against GABA( B)receptors were
      also used to detect a potential protein expression modulation. No asymmetry was
      observed by autoradiography in the intact and deafferented MVN at any time (5 h
      to 8 days) following the lesion and for any of the oligonucleotide probes used.
      Also, no difference in the alpha1, beta2, beta3 and gamma2 of the GABA(A) and in
      the GABA(B) receptor immunohistochemical signal could be detected between the
      intact and deafferented vestibular nuclei at any time following the lesion. Our
      data suggest that GABA(A) and GABA Breceptor density changes most probably were
      not involved in the early stage of the vestibular compensation process, i.e., in
      the restoration of a normal resting discharge of the deafferented vestibular
      neurons and consequently in the recovery of a normal posture and eye position.

PMID- 15452675
TI  - Ipsilateral and contralateral motor inhibitory control in musical and
      vocalization tasks.
AB  - The inhibitory motor control mechanisms in human singing and vocalization are not
      well understood. Using transcranial magnetic stimulation (TMS), we show that
      singing resulted in right-sided prolongation of ipsilateral silent period and
      bilateral reduction in contralateral silent period. Reading led to reduced
      contralateral silent period duration with right-sided TMS only, but no
      significant inhibitory changes, both ipsilateral and contralateral, were evident
      with humming. The findings support the presence of enhanced interhemispheric
      inhibitory motor interaction during singing, as opposed to reading tasks, in
      dynamic word generation coupled with production of melody.

PMID- 15452676
TI  - Determination of human IgG by solid-substrate room-temperature phosphorescence
      immunoassay based on an antibody labeled with nanoparticles containing rhodamine
      6G luminescent molecules.
AB  - Luminescent 50-nm silicon dioxide nanoparticles containing both types of
      rhodamine 6G (R; particles denoted R-SiO2) were synthesized by the sol-gel
      method. In the presence of Pb(Ac)2 as a heavy atom perturber the particle can
      emit the intense and stable room-temperature phosphorescence (RTP) signal of R on
      a polyamide membrane, with lambda(ex)max/ lambda(em)max=470/635 nm for R. Our
      research indicates that the specific immune reaction between goat-anti-human IgG
      antibody labeled with R-SiO2 and human IgG can be carried out quantitatively on a
      polyamide membrane, and the phosphorescence intensity was enhanced after the
      immunoreaction. Thus a new method for solid-substrate room-temperature
      phosphorescence immunoassay (SS-RTP-IA) for determination of human IgG was
      established on the basis of antibody labeled with the nanoparticles containing
      binary luminescent molecules. The linear range of this method is 0.0624-20.0 pg
      spot(-1) of human IgG (corresponding to a concentration range of 0.156-50.0 ng
      mL(-1), sample volume 0.40 microL spot(-1)). The regression equations of the
      working curves are DeltaIp = 71.27+7.208 m(IgG) (pg spot(-1)) (r = 0.9996).
      Detection limits calculated as 3 Sb/k are 0.022 pg spot(-1). Compared with the
      same IA using fluorescein isothiocyanate (FITC) as the marker the new method was
      more sensitive and had a wider linear range. After elevenfold replicate
      measurement RSD are 4.5 and 3.6% for samples containing 0.156 and 50.0 ng mL(-1)
      IgG, respectively. This method is sensitive, accurate, and of high precision.

PMID- 15452677
TI  - Analysis of inorganic mercury species associated with airborne particulate
      matter/aerosols: method development.
AB  - This paper describes a method for speciation of Hg associated with airborne
      particulate matter. This method uses a mini-sampler for sample collection and
      analysis, thermal desorption for separating Hg species, and inductively coupled
      plasma mass spectrometry (ICP-MS) for identification and quantification of Hg.
      Coal fly ash spiked with different Hg compounds (e.g. Hg0, HgCl2, HgO, and HgS)
      was used for qualitative calibration. A standard reference material with a
      certified value for Hg concentration was used to evaluate the method. When the
      temperature of the furnace was programmed at a linear rate of increase of 50
      degrees min(-1), different Hg compounds could clearly be separated. Three
      airborne particulate matter samples were collected in parallel in Toronto, ON,
      Canada and analyzed using this method. Reproducible results were obtained and
      Hg0, HgCl2, HgO, and HgS species from these samples were detected.

PMID- 15452678
TI  - Ozone monitoring in a Mediterranean forest using diffusive and continuous
      sampling.
AB  - Ambient ozone was measured in a forest in Castelporziano (Italy) characterised by
      the prevailing presence of Holm-oak trees (Quercus ilex L.) from June to November
      2003. Two methods for measuring ozone were used: long-term monitoring using
      diffusive samplers at three heights within the canopy, and continuous monitoring
      at two heights using the UV method. Results for one week mean ozone levels above
      and below the canopy from the diffusive samplers were compared to those obtained
      using the automatic analyser at the same levels. A good correlation between the
      two sampling techniques was found. Continuous monitoring showed a daily cycle
      with a midday maximum and a nocturnal minimum. While the forest floor
      consistently had the lowest ozone concentration, there were no differences during
      most daytime hours. The midday maximum is clearly due to downward mixing with O3
      rich air from above. The night-time ozone decay within the canopy is the result
      of dry deposition of O3 and most likely due to reaction with biogenically
      produced NO. AOT40 within and above the canopy mostly exceeded the critical
      levels.

PMID- 15452679
TI  - Monitoring the degradation and solubilisation of butyltin compounds during in
      vitro gastrointestinal digestion using "triple spike" isotope dilution GC-ICP-MS.
AB  - An in vitro gastrointestinal digestion approach in combination with species
      specific isotope dilution analysis has been employed for the first time to study
      the transformation reactions as well as the solubilisation of butyltin species
      throughout a simulated human digestion. Different sample preparation procedures
      were assayed in order to avoid problems derived from lack of isotope
      equilibration between the endogenous and the isotopically-enriched added species.
      A "triple spike" approach, which can be used to calculate the corrected
      concentrations of mono-, di-, and tributyltin (MBT, DBT and TBT, respectively),
      as well as six interconversions, was employed throughout this work. In order to
      calculate and compare the species degradation factors, a triple spike solution
      containing each butyltin species enriched in a different isotope was added to the
      simulated gastric and intestinal fluids before the digestion procedures in the
      presence and in the absence of a solid biological matrix (commercial mussel
      tissue). Additionally, by analysing the soluble and insoluble fractions resulting
      from the simulated digestion of a commercial mussel tissue (gastric and gastric
      plus intestinal digestion), total mass balances for each butyltin compound could
      be derived. For this purpose, the isotopically-enriched species were added after
      the enzymatic digestions in order to avoid problems derived from lack of isotope
      equilibration. The mass balances provided information not only about the
      solubilisation but also about the degradation of the butyltin species during the
      digestion procedures. Good agreement between the degradation factors calculated
      under all experiments performed in this work and between those reported in
      previous works were obtained. The most serious degradation observed was that of
      DBT to produce MBT, whereas slight degradations of TBT and MBT were detected.
      Moreover, a worrying 61% of the original total butyltin content present in a
      commercial mussel tissue was found to be solubilised after complete simulated
      gastrointestinal digestion, with minimal degradation of TBT.

PMID- 15452680
TI  - Multiresidue analysis of phenylurea herbicides in environmental waters by
      capillary electrophoresis using electrochemical detection.
AB  - A rapid multiresidue method has been developed for the analysis of seven
      phenylurea herbicides in the presence of two s-triazines in environmental waters.
      A simple end-column electrochemical detector was used in combination with a
      commercially-available capillary electrophoresis instrument with UV detection.
      The determination of phenylurea pesticides using micellar electrokinetic
      capillary chromatography with electrochemical detection represents the first such
      determination that has been reported. In both detection systems, linear ranges
      were obtained for the seven phenylurea herbicides at concentrations lower than
      2.0x10(-5) mol l(-1), in 0.020 mol l(-1) phosphoric acid at pH 7.0 and containing
      0.020 mol l(-1) of sodium dodecylsulfate, in order to obtain selectivity in the
      additional separation by a micellar distribution process. Under these conditions
      a detection limit lower than 5.0x10(-6) mol l(-1) (0.25 pmol of pesticide) was
      achieved for most of them. The pesticides were resolved in less than 30 min.

PMID- 15452681
TI  - Effects of isradipine on methamphetamine-induced changes in attentional and
      perceptual-motor skills of cognition.
AB  - RATIONALE: While the effects of d-amphetamine in increasing performance have been
      established, there is a paucity of information on the effects of methamphetamine
      on cognition in drug-naive subjects, and no published information on the effects
      of intravenous methamphetamine administration in dependent individuals. The
      dihydropyridine-class calcium channel antagonist, isradipine, has been posited as
      a putative treatment to prevent methamphetamine-associated hypertensive crisis
      and its sequelae. Yet, isradipine's effects on cognitive performance in
      methamphetamine-dependent individuals are not known. OBJECTIVE: Since individuals
      whose dependence on methamphetamine is attributable to the need to enhance
      performance may be loath to take a cognition-impairing medication, even for the
      treatment of life-threatening hypertensive crisis, it would be important to
      determine isradipine's effects on performance. METHODS: We therefore examined in
      a blinded, placebo-controlled, crossover design the cognitive effects of low and
      high doses of intravenous methamphetamine (15 mg and 30 mg, respectively) in both
      the presence and absence of isradipine. RESULTS: Intravenous d-methamphetamine
      produced dose-dependent increases in attention, concentration, and psychomotor
      performance. Isradipine, both with and without methamphetamine, had a modest
      effect to decrease attention. CONCLUSION: Our results do not support the further
      testing of isradipine as a medication for improving the cognitive impairments
      that have been associated with chronic methamphetamine use.

PMID- 15452682
TI  - Paroxetine combined with a 5-HT(1A) receptor antagonist reversed reward deficits
      observed during amphetamine withdrawal in rats.
AB  - RATIONALE: "Diminished interest or pleasure" in rewarding stimuli is an affective
      symptom of amphetamine withdrawal and a core symptom of depression. An
      operational measure of this symptom is elevation of brain stimulation reward
      thresholds during drug withdrawal. Data indicated that increasing serotonin
      neurotransmission by co-administration of the selective serotonin reuptake
      inhibitor (SSRI) fluoxetine and the serotonin-1A receptor antagonist p-MPPI
      reversed reward deficits observed during drug withdrawal (Harrison et al. 2001).
      OBJECTIVES: We tested the hypothesis that increased serotonergic and
      noradrenergic neurotransmission, using the SSRI paroxetine which also inhibits
      noradrenaline reuptake, would alleviate affective aspects of amphetamine
      withdrawal. METHODS: A discrete-trial, current-threshold, self-stimulation
      procedure was used to assess brain reward function. The effects of paroxetine and
      p-MPPI alone and in combination were assessed in non-drug-withdrawing animals. We
      assessed also the effects of paroxetine and p-MPPI alone and in combination on
      reward deficits associated with amphetamine withdrawal. RESULTS: Paroxetine or p
      MPPI alone had no effect on thresholds, while the co-administration of p-MPPI (3
      mg/kg) and paroxetine (1.25 mg/kg) elevated thresholds in non-withdrawing rats.
      Amphetamine withdrawal resulted in threshold elevations. The co-administration of
      p-MPPI and paroxetine reduced the duration of amphetamine-withdrawal-induced
      reward deficits. CONCLUSIONS: Increased serotonergic and noradrenergic
      neurotransmission decreased reward function in non-withdrawing rats, while the
      same treatment reversed reward deficits associated with amphetamine withdrawal.
      Considering that paroxetine acts on both the serotonin and noradrenaline
      transporter, these results indicate that the affective symptoms of amphetamine
      withdrawal, similar to non-drug-induced depressions, may be, in part, mediated
      through reduced serotonergic and noradrenergic neurotransmission.

PMID- 15452683
TI  - Flumazenil-precipitated withdrawal in healthy volunteers following repeated
      diazepam exposure.
AB  - RATIONALE: Parametric preclinical studies of the benzodiazepine antagonist
      flumazenil have contributed to the understanding of the physical dependence
      associated with chronic benzodiazepine use. However, few parametric studies have
      been conducted in human participants. OBJECTIVE: This study was designed to
      assess the effect of duration of benzodiazepine exposure on the intensity of
      flumazenil-precipitated withdrawal in healthy volunteers. METHOD: Participants
      were randomly assigned to receive either oral diazepam (15 mg/70 kg; n=10) or
      placebo (n=8) capsules nightly for 28 days. Effects of flumazenil (1 mg/70 kg,
      intravenously administered) were assessed in challenge sessions conducted before
      capsule ingestion, and after 1, 7, 14, and 28 days of capsule ingestion. RESULTS:
      Flumazenil produced a profile of participant-rated effects consistent with
      benzodiazepine withdrawal that peaked immediately after completion of the 5-min
      flumazenil injection and rapidly dissipated thereafter. The magnitude of these
      effects was comparable after 7, 14, and 28 days of diazepam. Flumazenil also
      produced modest elevations in blood pressure and decreases in skin temperature in
      the diazepam group, both of which were sustained throughout the approximate 60
      min session. CONCLUSIONS: These findings support previous human research studies
      indicating that flumazenil precipitates withdrawal after short chronic exposure
      to benzodiazepines and suggests that duration of exposure does not influence the
      intensity of withdrawal beyond the first week of exposure.

PMID- 15452684
TI  - Risperidone diminishes cocaine-induced craving.

PMID- 15452685
TI  - Time course of the effects of the serotonin-selective reuptake inhibitor
      sertraline on central and peripheral serotonin neurochemistry in the rhesus
      monkey.
AB  - RATIONALE: Fundamental questions remain regarding the actions of the selective
      serotonin reuptake inhibitors (SSRIs). OBJECTIVES: To examine the time course of
      central and peripheral neurochemical effects of sertraline (SER) in non-human
      primates. METHODS: SER (20 mg/kg, p.o.) or placebo were administered daily for 4
      weeks to two groups of six young adult male rhesus monkeys. Both groups received
      placebo during a 3-week baseline lead-in period and for 6 weeks after
      discontinuation. Blood and cisternal cerebrospinal fluid (cCSF) samples were
      obtained on days -21, -14, -7, 0, +3, +7, +14, +21, +28, +35 and +70. RESULTS: In
      animals receiving SER, mean (+/-SD) levels of cCSF serotonin (5-HT) increased
      from 38.6+/-9.0 pg/ml at baseline to 128+/-46.4 pg/ml during treatment (paired
      t=4.17, P=0.014). Concentrations of cCSF 5-HT were 290% of baseline on day 0 (+3
      h), ranged from 260% to 436% of baseline during treatment, and returned to
      baseline 7 days after discontinuation. Levels of cCSF 5-hydroxyindoleacetic acid
      declined to 51+/-2.0% of baseline by day +3 and remained at similarly reduced
      levels during treatment. Plasma drug levels and decrements in platelet 5-HT were
      similar to those seen in patients. CONCLUSIONS: SER rapidly and substantially
      increases cCSF levels of 5-HT in primates, the extent of elevation is relatively
      constant during prolonged administration, and values return to baseline shortly
      after discontinuation. The results suggest that response latency for SSRIs in
      depression is not due to gradually increasing brain extracellular fluid 5-HT
      levels and tend not to support theories that posit SSRI response latency as being
      due to autoreceptor desensitization, transporter downregulation, or drug
      accumulation.

PMID- 15452686
TI  - Rolipram reduces the inotropic tachyphylaxis of glucagon in rat ventricular
      myocardium.
AB  - Glucagon increases cardiac contractility through G(s) protein-coupled glucagon
      receptors, but the inotropic responses fade. The fade could be due to receptor
      desensitisation or to the action of phosphodiesterases (PDE), or to both
      mechanisms. We investigated the effects of the PDE4 inhibitor rolipram (1 microM)
      on the inotropic and cAMP-responses to glucagon in paced right ventricular strips
      of the rat heart. Responses to the partial agonist dobutamine, mediated through
      beta(1)-adrenoceptors, were studied for comparison. Glucagon increased
      contractility (-logEC(50)M=7.3 for maximum responses with E(max)=32% of the
      response to 9 mM Ca(2+)), but the responses tended to fade (-logEC(50)M=7.1 for
      faded responses with E(max)=11.5%). Dobutamine (-logEC(50)M=5.8, E(max)=56%)
      produced positive inotropic effects that did not fade. Rolipram did not affect
      basal contractility and cAMP levels. Rolipram enhanced the contractile responses
      to glucagon and reduced fade (-logEC(50)M=7.5 and 7.3 with E(max)=74% and 45% for
      maximum and faded responses respectively). The response to glucagon (0.1 microM)
      completely faded in the absence of rolipram, but only partially faded and then
      remained stable in the presence of rolipram (1 microM). Rolipram enhanced
      contractile responses to dobutamine (-logEC(50)M=6.0, E(max)=75%). Dobutamine (3
      microM), but not glucagon (0.1 microM), increased tissue levels of cAMP.
      Consistent with the inotropic data, rolipram caused glucagon to augment cAMP and
      enhanced the effects of dobutamine. Thus, PDE4 activity limits the responses
      mediated through both glucagon receptors and beta(1)-adrenoceptors. PDE4
      catalysed hydrolysis of cAMP contributes to the inotropic tachyphylaxis of
      glucagon.

PMID- 15452687
TI  - Epsilon protein kinase C lengthens the quiescent period between spontaneous
      contractions in rat ventricular cardiac myocytes and trabecula.
AB  - We have observed a lengthening of the duration between spontaneous cardiac
      contractions under conditions that preferentially activate the epsilon protein
      kinase C (epsilonPKC) isozyme. Therefore, we investigated whether this response
      could be selectively mediated by epsilonPKC in neonatal cardiac myocytes (NCMs)
      and adult rat ventricular trabeculae. Contraction of NCMs was monitored using
      light scattering techniques and trabecular force generation was monitored in
      tissue baths using a force transducer. The involvement of the epsilonPKC isozyme
      was confirmed using an epsilonPKC-selective translocation inhibitor and Western
      blot translocation assays. In NCMs 3 nM 4-beta phorbol 12-myristate-13-acetate
      (PMA) treatment preferentially activates (translocates) epsilonPKC. In this study
      3 nM 4-beta PMA induced a 2-fold increase in contractile amplitude and a
      approximately 14-fold increase in the quiescent period between contractions in
      NCMs. Extracellular adenosine 5'-triphosphate (ATP) also enhanced contractile
      amplitude by 1.7-fold and the quiescent period duration by 8-fold. The
      enhancement of quiescent period duration was attenuated by an epsilonPKC
      selective translocation inhibitor. To investigate these relationships in intact
      myocardium, we studied spontaneously beating adult rat ventricular trabecula. In
      these fibers contractile amplitude was only modestly enhanced; however, the
      quiescent period was lengthened by 4.5-fold following a 15-min exposure to 3 nM 4
      beta PMA. 4-beta PMA treatment also promoted arrhythmogenesis and increased the
      association of epsilonPKC with the particulate fraction in these fibers. Our
      results suggest that epsilonPKC may influence a specific phase of ventricular
      myocyte spontaneous beating. A better understanding of epsilonPKC modulation of
      spontaneous cardiac contraction may improve our understanding of the molecular
      events contributing to ventricular automaticity.

PMID- 15452688
TI  - Epidemiology of hip fractures in 2002 in Rabat, Morocco.
AB  - Hip fracture has never been studied before, either in Morocco or in the adjacent
      countries of the south bank of the Mediterranean Sea. The aim of this study was
      to investigate the incidence rate of hip fracture in 2002 in Rabat Province, a
      large area in the northwest of The Kingdom of Morocco, by the use of register
      information and medical records collected from the five public hospitals of the
      region. The hip fracture data were restricted to cervical or trochanteric types.
      There was a total of 150 hip fractures (83 in women and 67 in men) in the over-50
      year-old population in the Province of Rabat during 2002. The age-adjusted 1-year
      cumulative incidence of hip fracture was 52.1/100,000 [95% confidence interval
      (CI) 40.9-63.3/100,000] in women and 43.7/100,000 (95% CI 33.3-52.2/100,000) in
      men. The standardized incidence rate against the 1985 US population was
      80.7/100,000 (95% CI 78.5-93.0/100,000) for women and 58.5/100,000 (95% CI 47.9
      68.1/100,000) for men. The mean (standard deviation) age of patients with a hip
      fracture was 70.7 (9.4) years for women and 70.4 (10.0) years for men. The
      overall female-to-male ratio of hip fracture was 1.19 for age-adjusted hip
      fracture incidence and 1.30 for standardized incidence. A marked increase in
      incidence rate was found for both men and women with increasing age, becoming
      exponential after the age of 50 years. The mean age for hip fracture was 70.7
      (9.4) years in women and 70.4 (10.0) years in men (P > 0.05). Women had a
      cervical-to-trochanteric ratio of 0.97 compared to men, at 1.03. The
      characteristics of hip fractures described in this study suggest that fragility
      fractures occur in North Africa, although substantially less frequently than in
      most European, North American and Asian countries but more frequently than sub
      Saharan African countries, in agreement with the north-south gradient observed in
      the epidemiology of osteoporosis. The low incidence of hip fragility fracture
      rate is most likely the result of reduced longevity in Morocco.

PMID- 15452689
TI  - The efficacy of acute administration of pamidronate on the conservation of bone
      mass following severe burn injury in children: a double-blind, randomized,
      controlled study.
AB  - Bone loss is a known complication of severe burn injury. It is, in part, due to
      increased endogenous glucocorticoids that contribute to the reduction in bone
      formation and osteoblast differentiation, hypercalciuria secondary to
      hypoparathyroidism, and vitamin D deficiency. In this study we attempted to
      prevent post-burn bone loss by acute intravenous administration of the
      bisphosphonate pamidronate. We enrolled 43 children, with burns of > 40% total
      body surface area, in a randomized, double-blind, placebo-controlled study,
      administering the study drug within 10 days of burn injury and again 1 week
      later. Dual energy X-ray absorptiometry was performed prior to drug therapy, at
      hospital discharge and at 6 months post-burn. Urine specimens were obtained at
      baseline and discharge for determination of calcium and free deoxypyridinoline.
      Blood was obtained along with the urine specimens for measurement of intact
      parathyroid hormone (iPTH) and ionized calcium (Ca) levels. Following doxycycline
      labeling, intra-operative iliac crest bone biopsies were obtained, and bone
      histomorphometry was determined. At time of discharge there were no differences
      in total body bone mineral content (BMC), but lumbar spine BMC was significantly
      higher in the pamidronate group (P < 0.005). By 6 months post-burn the
      differences in lumbar spine BMC persisted, but, now, total body BMC was
      significantly higher in the pamidronate group (P < 0.05). Bone histomorphometry
      and levels of urine Ca and free deoxypyridinoline failed to show significant
      increases in bone formation or decreases in bone resorption. Pamidronate did not
      exacerbate the hypocalcemia in burn patients. In summary, acute intravenous
      pamidronate administration following burns may help to preserve bone mass,
      perhaps by inhibiting the glucocorticoid-induced apoptosis of osteoblasts and
      osteocytes.

PMID- 15452690
TI  - Cortical and trabecular bone density and structure in anorexia nervosa.
AB  - The aim of the study was to examine bone density and architecture with three
      different measurement methods in a sample of young women with anorexia nervosa
      (AN) and in an age-matched control group of women. Three-dimensional periphery
      quantitative computer tomography (3D-pQCT) at the ultradistal radius, a new
      technology providing measures of cortical and trabecular bone density and
      architecture, was performed, as well as quantitative ultrasound (QUS) at the
      heel, and dual energy X-ray absorptiometry (DXA) at the spine and hip. Thirty-six
      women with AN aged 18-30 years (mean duration of AN: 5.8 years) and 30 age
      matched women were assessed. Bone mineral density measured by DXA at the spine
      and hip, and broadband ultrasound attenuation measured by QUS at the heel were
      significantly lower in patients than controls. 3D-pQCT demonstrated a highly
      significant deficit in the absolute number of bone trabecules and a significant
      reduction of cortical thickness. Severity of underweight was significantly
      associated with bone deficits at the hip measured by DXA. 3D-pQCT revealed mostly
      deficits of cortical bone related with age of onset of eating disorder. Using
      three different methods to measure bone density and bone structure at the hip,
      spine, heel and ultradistal radius, significant deficits in bone mineral density
      both in trabecular and cortical bone, as well in trabecular structure could be
      demonstrated in the AN patients.

PMID- 15452691
TI  - Voiding function in pregnancy and puerperium.
AB  - Bladder function changes significantly in pregnancy. This study prospectively
      examined voiding function in a nulliparous cohort. A total of 200 nulliparous
      women were seen twice during pregnancy and 2-5 months postpartum. Flowmetry,
      ultrasound estimation of residual urine and translabial ultrasound of bladder
      neck mobility were evaluated. The Liverpool nomograms were used to calculate
      maximum and average flow rate (MFR and AFR) centiles. Flowmetry was available on
      186 women at 6-18 weeks, 165 women at 32-39 weeks and 162 women 2-5 months
      postpartum. Voided volumes decreased from 253 to 180 ml during pregnancy
      (p<0.001), increasing again to 198 ml postpartum. MFR centiles increased during
      pregnancy [from 49 (SD 28) to 58 (SD 29), p=0.003], and this trend continued
      postpartum [to 61.8 (SD 26.8), p<0.001]. Changes correlated weakly but
      significantly with changes in several parameters of bladder neck mobility (e.g.
      urethral rotation and MFR centiles, r=0.182, p=0.027). MFR and AFR centiles
      increase in pregnancy and with childbirth, and increases correlate weakly with
      changes in bladder neck mobility.

PMID- 15452692
TI  - An ambispective observational study in the safety and efficacy of posterior
      colporrhaphy with composite Vicryl-Prolene mesh.
AB  - There is increasing evidence to show that the use of surgical meshes reduces
      recurrence rates of hernia repair and anterior vaginal wall prolapse. The aim of
      this study was to determine the safety and efficacy of posterior colporrhaphy
      with mesh in patients with posterior vaginal prolapse. An ambispective
      observational study involving 90 patients was conducted with retrospective chart
      review and prospective subjective and objective assessments at the end of a 1
      year study period. Apart from 2 of 90 (2.2%) minor hematoma incidents, there was
      no other major perioperative morbidity. Prevalence of common prolapse complaints
      of vaginal lump sensation, constipation, defecation difficulty and dyspareunia
      all improved significantly postoperatively (p<0.001). Surgical correction was
      achieved in 27 of 31 (83.9%) at 6 months and beyond. There was no mesh infection
      but minor vaginal mesh protrusion was found in 7 of 90 (7.8%) patients at 6-12
      weeks and 4 of 31 (12.9%) patients at 6 months and beyond. All these were treated
      easily with trimming without the need of mesh removal. We conclude that posterior
      colporrhaphy with mesh is effective in treating posterior vaginal prolapse in
      short term.

PMID- 15452693
TI  - Preferred plasma volume expanders for critically ill patients: results of an
      international survey.
AB  - OBJECTIVE: Criteria for plasma volume expander selection in critically ill
      patients remain controversial. This study evaluated preferences of intensivists
      regarding plasma volume expanders. DESIGN: International survey using a 75-item
      questionnaire. PARTICIPANTS AND SETTING: All members of the European and French
      Societies of Intensive Care Medicine (n=2,415 in 1,610 adult ICUs in Europe and
      elsewhere) were invited to participate, and 577 (24%) working in 515 ICUs (32%)
      returned completed questionnaires. RESULTS: Among respondents, 17% used
      crystalloids alone as their first-choice strategy, 18% colloids alone, and 65%
      both. Colloids alone were often chosen in patients with cirrhosis (42%),
      coagulation disorders (42%), or adult respiratory distress syndrome (39%); and
      crystalloids in patients with dehydration (85%), drug overdose (59%), or acute
      renal failure (49%). First-line plasma expanders were as follows: isotonic
      crystalloids (81%), starches (55%), gelatins (35%), albumin (7%), plasma (6%),
      dextrans (4%), and hypertonic crystalloids (2%). Colloids alone were used more
      frequently in the United Kingdom (40%), starches in Germany (81%) and The
      Netherlands (66%), and gelatins in the United Kingdom (68%). The main factors
      behind preferences for first-line plasma volume expanders were time to volume
      loss correction, duration of effect, adverse events, and cost. CONCLUSIONS:
      Colloids are widely used as first-line treatment, usually in combination with
      crystalloids. Starches are the most widely used colloids in Europe, where albumin
      use is declining. However, strategies vary widely across clinical situations and
      countries.

PMID- 15452694
TI  - [Tissue engineering of the urinary bladder].
AB  - In tissue engineering of the urinary bladder with autologous cell
      transplantation, high differentiation of the cells cultivated in vitro on
      biocompatible membranes is essential for the functionality of the tissue
      constructs after implantation. The terminal differentiation of superficial
      urothelial cells has a key role because of the barrier function of these cells
      against urine. The aim of this study was to determine optimized conditions for
      the creation of terminally differentiated urothelium to cover large membrane
      surfaces. This can bring us closer to the goal of using functioning tissue
      constructs in clinical trials.

PMID- 15452695
TI  - [CTA of carotid artery with different scanner types].
AB  - Noninvasive modalities like CTA are increasingly replacing selective angiography
      in the evaluation of carotid artery stenosis. Dedicated scan protocols and
      contrast injection techniques are mandatory for the morphological assessment of
      carotid artery stenosis. These protocols need to be adapted to different scanner
      types. The delineation of plaque components and the residual lumen is improved
      with high resolution scan protocols and dedicated reconstruction algorithms. The
      exact delineation of in-stent stenosis remains limited. Standardization of
      postprocessing is crucial in order to attain reproducible results. Multislice
      spiral CT allows reliable grading of carotid artery stenosis. Relevant venous
      opacification and pulsation artifacts have to be expected with 4-slice scanners,
      the short scan time of the latest CT scanners minimize these problems.

PMID- 15452696
TI  - [Stents in the treatment of intracranial atherosclerotic stenoses].
AB  - The treatment of intracranial atherosclerotic stenoses, which account for 10-15%
      of all ischemic strokes, is technically feasible for few years by the use of new
      flexible stent devices. Especially patients who fail best medical treatment have
      a poor prognosis and stenting becomes a reasonable treatment option. Herein we
      discuss treatment concepts and the principles of stent placement against the
      background of epidemiology and pathophysiologic basics.

PMID- 15452698
TI  - Energetic expenditure during vocalization in pups of the subterranean rodent
      Ctenomys talarum.
AB  - Theoretical signaling models predict that to be honest, begging vocalizations
      must be costly. To test this hypothesis, oxygen consumption was measured during
      resting and begging (i.e., vocalizing) activities in pups of the subterranean
      rodent Ctenomys talarum by means of open-flow respirometry. No statistical
      differences in individual oxygen consumption between resting and calling pups
      ranging in age from day 2 to day 20 were found. Given these data, begging calls
      of C. talarum could not be considered as honest advertisements of offspring need,
      contrary to what suggested by the behavioral observations of the mother and pups
      during the nestling period.

PMID- 15452697
TI  - [Diagnostic evaluation of carotid artery stenoses with multislice CT angiography.
      Review of the literature and results of a pilot study].
AB  - BACKGROUND: The accurate evaluation of carotid artery stenoses is important for
      therapeutic decision making. Catheter digital subtraction angiography (DSA) still
      represents the gold standard, while the advent of multislice CT (MSCT) has led to
      improved temporal and spatial resolutions of CTA. MATERIAL AND METHODS: In a
      pilot study, we investigated 14 diseased vessels in 9 symptomatic patients (7m,
      2f; mean age 60.7+/-10,9 years) comparing biplanar DSA with standardized 16-slice
      MS-CTA. The degree of stenosis was evaluated in a consensus reading following
      modified NASCET criteria. RESULTS: DSA demonstrated 4 occlusions, 5 high-grade
      stenoses (>70%) and 5 lower-grade stenoses (<70%). One dissecting, infrapetrous
      stenosis was not adequately quantified by CTA due to a close topographic relation
      to the skull base. In the carotid bifurcation (n=13), an excellent correlation
      was demonstrated between DSA and CTA with a correlation coefficient of 0.99.
      CONCLUSION: MS-CTA has a good diagnostic potential in the evaluation of carotid
      artery stenoses. Larger studies will need to demonstrate the relative diagnostic
      value for different subtypes of stenosis and for different reader experience
      levels.

PMID- 15452699
TI  - Gastroliths in Yanornis: an indication of the earliest radical diet-switching and
      gizzard plasticity in the lineage leading to living birds?
AB  - Yanornis martini is an Early Cretaceous basal ornithurine bird. Its fish-eating
      diet was previously recognized from a discrete mass of disarticulated fish
      remains discovered in its abdominal region. A new complete and articulated
      specimen of Yanornis martini preserves abundant in-situ gastroliths such as have
      been associated with a herbivorous diet. We suggest that the occurrence of
      gastroliths in this specimen, fish remains in a second, and the lack of
      gastroliths in three others, is consistent with diet-switching in Yanornis
      martini. Incompatibility of the preserved data with explanations of the grit as
      an artifact of preservation or result of accidental ingestion is discussed. This
      discovery indicates the earliest presence of intermittent diet change (and
      associated gizzard plasticity) observed in extant birds seasonally and in
      response to changes in available food sources.

PMID- 15452700
TI  - Pheromone-modulated behavioral suites influence colony growth in the honey bee
      (Apis mellifera).
AB  - The success of a species depends on its ability to assess its environment and to
      decide accordingly which behaviors are most appropriate. Many animal species,
      from bacteria to mammals, are able to communicate using interspecies chemicals
      called pheromones. In addition to exerting physiological effects on individuals,
      for social species, pheromones communicate group social structure. Communication
      of social structure is important to social insects for the allocation of its
      working members into coordinated suites of behaviors. We tested effects of long
      term treatment with brood pheromone on suites of honey bee brood rearing and
      foraging behaviors. Pheromone-treated colonies reared significantly greater brood
      areas and more adults than controls, while amounts of stored pollen and honey
      remained statistically similar. Brood pheromone increased the number of pollen
      foragers and the pollen load weights they returned. It appeared that the
      pheromone-induced increase in pollen intake was directly canalized into more
      brood rearing. A two-way pheromone priming effect was observed, such that some
      workers from the same age cohorts showed an increased and extended capacity to
      rear larvae, while others were recruited at significantly younger ages into
      pollen-specific foraging. Brood pheromone affected suites of nursing and foraging
      behaviors allocating worker and pollen resources associated with an important
      fitness trait, colony growth.

PMID- 15452702
TI  - Signal transduction pathways linking polyamines to apoptosis.
AB  - Polyamines are important multifunctional cellular components and are classically
      considered as mediators of cell growth and division. Recently polyamines have
      been also implicated in cell death. Now it appears that polyamines are bivalent
      regulators of cellular functions, promoting proliferation or cell death depending
      on the cell type and on environmental signals. This review draws a picture about
      the role of polyamines in signalling pathways related to apoptotic cell death and
      the proposed molecular targets of these polycations at the level of the apoptotic
      cascade. Solid evidence indicates that polyamines may affect the mitochondrial
      and postmitochondrial phases of apoptosis, by modulating cytochrome c release
      from mitochondria and activation of caspases. Recently, polyamines have been also
      implicated in the regulation of the premitochondrial phase of apoptosis, during
      which upstream apoptotic signal transduction pathways are activated. The studies
      reviewed here suggest that polyamines may participate in loops involving
      interaction with signal transduction pathways and activation/expression of
      proteins that may control cell death or cell growth.

PMID- 15452701
TI  - The evolutionary processes of mitochondrial and chloroplast genomes differ from
      those of nuclear genomes.
AB  - This paper first introduces our present knowledge of the origin of mitochondria
      and chloroplasts, and the organization and inheritance patterns of their genomes,
      and then carries on to review the evolutionary processes influencing
      mitochondrial and chloroplast genomes. The differences in evolutionary phenomena
      between the nuclear and cytoplasmic genomes are highlighted. It is emphasized
      that varying inheritance patterns and copy numbers among different types of
      genomes, and the potential advantage achieved through the transfer of many
      cytoplasmic genes to the nucleus, have important implications for the evolution
      of nuclear, mitochondrial and chloroplast genomes. Cytoplasmic genes transferred
      to the nucleus have joined the more strictly controlled genetic system of the
      nuclear genome, including also sexual recombination, while genes retained within
      the cytoplasmic organelles can be involved in selection and drift processes both
      within and among individuals. Within-individual processes can be either intra- or
      intercellular. In the case of heteroplasmy, which is attributed to mutations or
      biparental inheritance, within-individual selection on cytoplasmic DNA may
      provide a mechanism by which the organism can adapt rapidly. The inheritance of
      cytoplasmic genomes is not universally maternal. The presence of a range of
      inheritance patterns indicates that different strategies have been adopted by
      different organisms. On the other hand, the variability occasionally observed in
      the inheritance mechanisms of cytoplasmic genomes reduces heritability and
      increases environmental components in phenotypic features and, consequently,
      decreases the potential for adaptive evolution.

PMID- 15452703
TI  - Spinal muscle forces, internal loads and stability in standing under various
      postures and loads--application of kinematics-based algorithm.
AB  - This work aimed to evaluate trunk muscle forces, internal loads and stability
      margin under some simulated standing postures, with and without external loads,
      using a nonlinear finite element model of the T1-S1 spine with realistic
      nonlinear load-displacement properties. A novel kinematics-based algorithm was
      applied that exploited a set of spinal sagittal rotations, initially calculated
      to minimize balancing moments, to solve the redundant active-passive system. The
      loads consisted of upper body gravity distributed along the spine with or without
      200 N held in the hands, either in the front of the body or on the sides.
      Nonlinear and linear stability/perturbation analyses at deformed, stressed
      configurations with a linear stiffness-force relationship for muscles identified
      the system stability and critical muscle stiffness coefficient. Predictions were
      in good agreement with reported measurements of posture, muscle EMG and
      intradiscal pressure. Minimal changes in posture (posterior pelvic tilt and
      lumbar flattening) substantially influenced muscle forces, internal loads and
      stability margin. Addition of 200 N load in front of the body markedly increased
      the system stability, global muscle forces, and internal loads, which reached
      anterior shear and compression forces of approximately 500 N and approximately
      1,200 N, respectively, at lower lumbar levels. Co-activation in abdominal muscles
      (up to 3% maximum force) substantially increased extensor muscle forces, internal
      loads and stability margin, allowing a smaller critical muscle coefficient. A
      tradeoff existed between lower internal loads in passive tissues and higher
      stability margins, as both increased with greater muscle activation. The strength
      of the proposed model is in accounting for the synergy by simultaneous
      consideration of passive structure and muscle forces under applied postures and
      loads.

PMID- 15452704
TI  - Radiographic outcome of vertebral bone bruise associated with fracture of the
      thoracic and lumbar spine in adults.
AB  - Bone bruising associated with long bone injury is a defined entity with known
      radiological, pathologic and clinical features. Vertebral bone bruise (VBB) has
      been described through magnetic resonance imaging (MRI) of the injured spine, but
      to date the consequences of this entity are unknown. The objective of this
      retrospective study was to describe the plain radiographic outcome of MRI-defined
      VBB associated with thoracic and lumbar spine fracture in adults, and to assess
      whether VBBs caused abnormalities of the bone-implant interface at instrumented
      levels. Levels of VBB were identified through analysis of the full spine MRI in a
      consecutive series of adult patients admitted to a spinal injuries unit for
      thoracic and lumbar spine fractures. The anterior wedge angles (AWAs) of thoracic
      and lumbar vertebrae demonstrating VBB were measured on radiographs taken at time
      of injury and at follow-up. Abnormalities of the bone--implant interface were
      recorded at instrumented levels associated with VBB on follow-up radiographs.
      Thirty VBBs were identified in 18 adult patients who had suffered 21 vertebral
      fractures. At an average follow-up of 19 months (range, 12--30 months), the mean
      AWAs of the VBB vertebrae at the time of injury and at the most recent follow-up
      were 3.5 degrees and 3.8 degrees , respectively (p=0.33, paired t-test). A total
      of 12 out of 30 (40%) bruised levels were instrumented in 13 out of 18 (72%)
      operated patients. No bone--implant interface failure was observed at these
      levels. It is concluded that VBB associated with thoracic and lumbar vertebral
      fracture in adult patients does not appear to cause significant progressive
      vertebral deformity or bone--implant interface failure.

PMID- 15452705
TI  - The orphan G-protein-coupled receptor GPR19 is expressed predominantly in
      neuronal cells during mouse embryogenesis.
AB  - G-protein-coupled receptors (GPCRs) are characterized by seven transmembrane
      domains and constitute the largest and structurally best-conserved family of
      signaling molecules. They are present in a diversity of organs and tissues and
      are involved in virtually all physiological processes. Here we report the
      expression of GPR19, an orphan GPCR, during mouse embryonic development and in
      the adult brain. Transcripts of GPR19 were detected early in embryonic
      development and were prominent in tissues of neuroectodermal origin. With ongoing
      differentiation, the localization of GPR19 transcripts became restricted to
      distinct regions of the developing brain, and the overall signal intensity
      declined in parallel. In the adult mouse, GPR19 showed high levels of
      transcription in several regions of the brain, including the olfactory bulb, the
      hippocampus, hypothalamic nuclei, and the cerebellum, and in testis. Lower levels
      of GPR19 expression were detected in heart, liver, and kidney. These data suggest
      that, amongst several other functions in the adult organism, GPR19 probably
      exerts its most characteristic effects during the early development of the
      nervous system.

PMID- 15452706
TI  - Eutopic endometrium and peritoneal, ovarian and bowel endometriotic tissues
      express a different profile of matrix metalloproteinases-2, -3 and -11, and of
      tissue inhibitor metalloproteinases-1 and -2.
AB  - Endometriosis is subsequent to the ability of endometrial glands to invade normal
      tissues. Matrix metalloproteinases (MMPs)--enzymes that mediate normal tissue
      turnover, including endometrial breakdown during menstruation-appear to be
      involved in this invasive process. Here, we examined the immunohistochemical
      expression of MMP-2, MMP-3, MMP-11, tissue inhibitor metalloproteinase (TIMP)-1
      and TIMP-2 in endometrium from women with (n=9) or without endometriosis (n=18)
      in comparison with peritoneal (n=20), ovarian (n=20) and colorectal endometriosis
      (n=20). Women with endometriosis showed decreased endometrial MMP-2 expression
      compared with women without endometriosis (mean+/-SD positive cells: 24.3+/-28.3%
      and 69.3+/-12.1%), together with loss of MMP-3 expression (0 versus 17.5%+/
      20.2). MMP-11, TIMP-1 and TIMP-2 expression was similar in the two groups.
      Endometrial MMP-2, -3 and -11 expression and TIMP-1 and -2 expression were
      similar in women with endometriosis and in those with peritoneal endometriosis.
      MMP-2, -3 and -11 expression was higher in colorectal endometriosis than in
      ovarian and peritoneal endometriosis. TIMP-2 expression was lower in colorectal
      endometriosis (P=0.0002) and ovarian endometriotic cysts (P=0.003) than in
      peritoneal endometriosis. TIMP-1 expression did not vary according to the
      location of endometriotic lesions. These results suggest that MMP-2 and -3 and
      TIMP-2 may be involved in the pathogenesis of endometriosis. Interestingly, MMP-2
      and -3 overexpression was related to the infiltrative nature of endometriotic
      lesions, with possible sequential expression from peritoneal to colorectal
      endometriosis.

PMID- 15452707
TI  - Structure of the cinnamyl-alcohol dehydrogenase gene family in rice and promoter
      activity of a member associated with lignification.
AB  - Analysis of lignification in rice has been facilitated by the availability of the
      recently completed rice genome sequence, and rice will serve as an important
      model for understanding the relationship of grass lignin composition to cell wall
      digestibility. Cinnamyl-alcohol dehydrogenase (CAD) is an enzyme important in
      lignin biosynthesis. The rice genome contains 12 distinct genes present at nine
      different loci that encode products with significant similarity to CAD. The rice
      gene family is diverse with respect to other angiosperm and gymnosperm CAD genes
      isolated to date and includes one member (OsCAD6) that contains a peroxisomal
      targeting signal and is substantially diverged relative to other family members.
      Four closely related family members (OsCAD8A-D) are present at the same locus and
      represent the product of a localized gene duplication and inversion. Promoter
      reporter gene fusions to OsCAD2, an orthologue of the CAD gene present at the bm1
      (brown midrib 1) locus of maize, reveal that in rice expression is associated
      with vascular tissue in aerial parts of the plant and is correlated with the
      onset of lignification. In root tissue, expression is primarily in the cortical
      parenchyma adjacent to the exodermis and in vascular tissue.

PMID- 15452708
TI  - Regulation of NaPi-IIa mRNA and transporter protein in chronic renal failure:
      role of parathyroid hormone (PTH) and dietary phosphate (Pi).
AB  - Chronic renal failure (CRF) is associated with a high fractional phosphate
      excretion (FEPi), secondary hyperparathyroidism, and resistance to parathyroid
      hormone (PTH). This study was undertaken to characterize the role of PTH and
      dietary Pi in the regulation of PTH/PTH-related peptide receptor (PTHrP-R) mRNA
      and NaPi-IIa mRNA and protein in CRF. The following groups of rats were studied:
      (1) sham-operated (control); (2) CRF: 6 weeks after 5/6 nephrectomy (NPX); (3)
      NPX and parathyroidectomy (NPX + PTX); (4) NPX rats fed a low-Pi diet (NPX + LP);
      (5) sham-operated rats fed a low-Pi diet (control + LP); (6) sham-operated after
      PTX (control + PTX). Expression of NaPi-IIa mRNA and PTH/PTHrP-R mRNA was
      determined in the renal cortex by Northern hybridization. NaPi-IIa protein
      abundance was determined in cortical brush border membranes by immunoblotting. In
      NPX rats creatinine clearance decreased to 40 +/- 4%, PTH/PTHrP-R mRNA to 52.1 +/
      2% and NaPi-IIa mRNA to 41.2 +/- 5.5% of control. The PTH/PTHrP-R and NaPi-IIa
      mRNA in the NPX + PTX and NPX + LP group was similar to that in NPX. NaPi-IIa
      protein abundance was reduced in NPX compared with control, but was increased
      dramatically in NPX + PTX and NPX + LP compared to NPX, paralleled by a decrease
      in FEPi. These findings suggest that the elevated FEPi in CRF is maintained by
      decreased NaPi-IIa mRNA and NaPi-IIa protein abundance. In contrast, the observed
      decrease in FEPi with PTX or LP diet in CRF is mediated, at least partly, by
      increased NaPi-IIa protein abundance with no change in NaPi-IIa mRNA, suggesting
      post-transcriptional regulation of the NaPi-IIa transporter.

PMID- 15452709
TI  - Novel outwardly rectifying anion conductance in Xenopus oocytes.
AB  - We describe a novel, strongly outwardly rectifying anion current in Xenopus
      laevis oocytes, that we have named I(Cl,Or)- The properties of I(Cl,Or) are
      different from those of any other anion conductance previously described in these
      cells. Typically, I(Cl,Or) amplitude was small when extracellular Cl- (Cle) was
      the permeant anion. However, when Cle was replaced by lyotropic anions I(Cl,Or)
      became evident as a time-independent current. (ICl,Or) was voltage dependent and
      showed a remarkable outwards rectification with little or no inwards tail
      current. The relative selectivity sequence determined from current amplitudes
      was: SCN- > or = ClO4- > I- > Br- > or = NO3- > Cl- x I(Cl,Or) was insensitive to
      Gd3+ but was blocked by micromolar concentrations of niflumic acid, DIDS or Zn2+.
      Furthermore, I(Cl,Or) was not affected by buffering intracellular Ca2+ with
      BAPTA. Low extracellular pH inhibited I(Cl,Or) with a pK of 5.8. We propose that
      I(Cl,Or) might result from activation of endogenous ClC-5-like Cl- channels
      present in Xenopus oocytes.

PMID- 15452710
TI  - Targeted in vivo expression of proteins in the calyx of Held.
AB  - The calyx of Held serves as a model for synaptic transmission in the mammalian
      central nervous system. While offering unique access to the biophysics of
      presynaptic function, studies addressing the molecular mechanisms of
      neurotransmitter exocytosis in this model have been mainly limited to
      pharmacological interventions. To overcome this experimental limitation we used
      stereotaxic delivery of viral gene shuttles to rapidly and selectively manipulate
      protein composition in the calyx terminal in vivo. Sindbis or Semliki Forest
      viruses encoding enhanced green fluorescent protein (EGFP) were injected into the
      ventral cochlear nucleus (VCN) of rats (postnatal days 7-21) and yielded bright
      fluorescence in cells of the VCN, including globular bushy cells with their axon
      and calyx terminal. Fluorescence imaging and three dimensional reconstructions
      visualized developmental changes in calyx morphology. Small cytoplasmic and
      synaptic vesicle proteins were successfully overexpressed in the calyx. We
      extended two-photon microscopy to obtain simultaneous fluorescence and infrared
      scanning gradient contrast images, allowing for efficient patch-clamp recordings
      from EGFP-labelled calyces in acute brain slices (postnatal days 9-14).
      Recordings of spontaneous miniature excitatory postsynaptic currents and short
      term depression in synapses overexpressing EGFP or synaptophysin-EGFP revealed
      normal synaptic function. Thus, Sindbis and Semliki Forest virus-directed
      overexpression of proteins in the calyx of Held provides a new avenue for
      molecular structure-function studies of mammalian central synapses.

PMID- 15452711
TI  - The Kv4.2 N-terminal restores fast inactivation and confers KChlP2 modulatory
      effects on N-terminal-deleted Kv1.4 channels.
AB  - The N-terminal end of the subunits of the voltage-gated K+ channel Kv1.4 is
      essential for their rapid N-type inactivation, but removal of the entire Kv4.2 N
      terminus slows inactivation only moderately. In this study, we investigated the
      effect of substituting the Kv4.2 N-terminal for that of Kv1.4 subunits. Despite
      the minor role of the Kv4.2 N-terminal in Kv4.2 inactivation and the limited
      degree of amino acid identity between Kv1.4 and Kv4.2 N-terminals, attachment of
      the Kv4.2 N-terminal to inactivation-deficient, N-terminal-deleted Kv1.4 subunits
      restored rapid inactivation. The Kv4.2 N-terminal/N-deleted Kv1.4 chimeric
      construct had inactivation kinetics like those of Kv4.2, inactivation voltage
      dependence resembling Kv1.4 and recovery from inactivation substantially faster
      than wild-type Kv1.4. Acceleration of reactivation appeared to be due to the
      ability of chimeric channels to recover from inactivation without passing through
      the open state. Co-expression of wild-type Kv1.4 with the K+ channel interacting
      protein-2 (KChIP2) did not alter Kvl.4 properties, but co-expression of KChIP2
      with Kv4.2 N-terminal/N-deleted Kv1.4 chimeric subunits significantly increased
      current expression and slowed inactivation without altering the rate of recovery
      from inactivation. We conclude that substitution of the Kv4.2 N-terminal for that
      of Kv1.4 transfers a variety of properties of Kv4.2, including inactivation time
      dependence, accelerated recovery from inactivation and interaction with KChIP2,
      to Kv1.4, indicating the ability of Kvl.4 subunits to display these properties
      and the sufficiency of the Kv4.2 N-terminal to convey them.

PMID- 15452712
TI  - Novel adenoviral vectors coding for GFP-tagged wtCFTR and deltaF508-CFTR:
      characterization of expression and electrophysiological properties in A549 cells.
AB  - E1/E3-deleted adenoviral vectors expressing an N-terminal green fluorescent
      protein (GFP) reporter gene fused to either wtCFTR (H5.040CMVEGFP-wtCFTR) or
      deltaF508-CFTR (H5.040CMVEGFP-deltaF508CFTR) were generated. To characterize the
      expression and activity, A549 cells were infected with vectors expressing GFP
      tagged and non-tagged forms of CFTR and deltaF508CFTR. CFTR activity was assayed
      in cell-attached and excised patches. For H5.040CMVEGFP-wtCFTR, forskolin
      dependent outward current was observed in cell-attached patches from 56 of 67 GFP
      positive cells. Single-channel conductances, open probability, mean open and mean
      closed time values for GFP-CFTR and CFTR were not significantly different. After
      excision, GFP-CFTR activity required ATP and exhibited a linear I-V relationship.
      For H5.040CMVEGFP-deltaF508CFTR, media were supplemented with 5 mM butyrate 16 h
      after infection. Forskolin-dependent outward current was observed in cell
      attached patches from 21 of 30 butyrate-treated GFP-positive cells and 0 of 8 GFP
      positive cells without butyrate. Single-channel conductances, open probability,
      mean open and mean closed time values for GFP-deltaF508CFTR and deltaF508CFTR
      were not significantly different. However, the increase in open probability with
      genistein was significantly smaller for GFP-deltaF508CFTR than for deltaF508CFTR.
      In excised patches, GFP-deltaF508CFTR activity required ATP and exhibited a
      linear I-V relationship. Despite the consistent detection of GFP-CFTR and GFP
      deltaF508CFTR channels in the plasma membrane by patch clamping, GFP fluorescence
      was observed only in intracellular regions and was not altered by butyrate. The
      data show that high levels of functional GFP-tagged CFTR channels can be
      expressed with these adenoviral vector constructs.

PMID- 15452713
TI  - Osmotic regulation of renal betaine transport: transcription and beyond.
AB  - Cells in the kidney inner medulla are routinely exposed to high extracellular
      osmolarity during normal operation of the urinary concentrating mechanism. One
      adaptation critical for survival in this environment is the intracellular
      accumulation of organic osmolytes to balance the osmotic stress. Betaine is an
      important osmolyte that is accumulated via the betaine/gamma-aminobutyric acid
      transporter (BGT1) in the basolateral plasma membrane of medullary epithelial
      cells. In response to hypertonic stress, there is transcriptional activation of
      the BGT1 gene, followed by trafficking and membrane insertion of BGT1 protein.
      Transcriptional activation, triggered by changes in ionic strength and water
      content, is an early response that is a key regulatory step and has been studied
      in detail. Recent studies suggest there are additional post-transcriptional
      regulatory steps in the pathway leading to upregulation of BGT1 transport, and
      that additional proteins are required for membrane insertion. Reversal of this
      adaptive process, upon removal of hypertonic stress, involves a rapid efflux of
      betaine through specific release pathways, a reduction in betaine influx, and a
      slower downregulation of BGT1 protein abundance. There is much more to be learned
      about many of these steps in BGT1 regulation.

PMID- 15452714
TI  - Protein and gene expression of Ca2+ channel isoforms in murine colon: effect of
      inflammation.
AB  - L-Type voltage-dependent Ca2+ channels (L-VDCC) mediate calcium influx in
      response to membrane depolarization and regulate intracellular processes such as
      contraction, secretion, neurotransmission, and gene expression. Colonic
      inflammation significantly attenuates calcium currents in smooth muscle; however,
      the basis for this remains unclear. In this study we examined the protein and
      mRNA expression of two isoforms of Ca(v)1.2, encoded by either exon la or 1b.
      Both isoforms were detected by Western blots, immunohistochemistry and RT-PCR in
      smooth muscle cells. Neither the protein nor mRNA expression measured by real
      time PCR of either isoforms was affected in colonic myocytes from dextran sulfate
      sodium-treated mice. In whole-cell voltage-clamp experiments, the amplitude of
      the calcium currents were decreased by almost 70% by inflammation. The calcium
      channel currents were attenuated by 50 +/- 3% by the c-src kinase specific
      inhibitor, PP2, in control cells but only 19 +/- 7% in cells from inflamed mice.
      These studies suggest that decreased calcium channel currents following colonic
      inflammation are not due to decreased expression but may result from altered
      regulation by the non-receptor cellular tyrosine kinase, c-src kinase.

PMID- 15452715
TI  - High glucose concentrations stimulate human monocyte sodium/hydrogen exchanger
      activity and modulate atherosclerosis-related functions.
AB  - In the present study, the effect of high (20 mM) glucose concentrations on human
      monocyte sodium/hydrogen exchanger (NHE1) activity, scavenger receptor CD36
      expression, cell adhesion, and cell migration have been investigated. Incubation
      with high glucose concentrations caused an increase in NHE1 activity, as
      estimated by internal pH and sodium-uptake measurements. This effect was specific
      for glucose, since it was not observed when monocytes were incubated in the
      presence of 20 mM of galactose, fructose, or mannitol. In addition, the
      activation of sodium uptake was inhibited by ethylisopropyl amiloride (EIPA),
      phloretine and cytochalasine B, and calphostin C. High glucose concentrations
      also increased the expression of CD36 receptors on the surface of monocytes and
      positively influenced monocyte migration and adhesion to laminin. EIPA added
      together with glucose counteracted these effects. The data of the present study
      suggest that a high glucose concentration can influence atherosclerosis-related
      monocyte functions via NHE1 activation.

PMID- 15452716
TI  - Concurrent measurements of the free cytosolic concentrations of H+ and Na+ ions
      with fluorescent indicators.
AB  - We report a method for the concurrent measurement of intracellular [Na+] ([Na+
      ]i) and pH (pHi) in cells co-loaded with SBFI, a Na+-sensitive fluorophore, and
      either carboxy SNARF-1 or SNARF-5F, H+-sensitive fluorophores. With the optical
      filters specified, fluorescence emissions from SBFI and either SNARF derivative
      were sufficiently distinct to allow the accurate measurement of [Na+]i and pHi in
      rat hippocampal neurons. Neither the Na+ sensitivity of SBFI nor the pH
      sensitivities of carboxy SNARF-1 or SNARF-5F was affected by the presence of a
      SNARF derivative or SBFI, respectively. In addition, the calibration parameters
      obtained in neurons single-loaded with SBFI, carboxy SNARF-1 or SNARF-5F were not
      significantly influenced by the presence of a second fluorophore. In contrast to
      the established weak sensitivity of SBFI for protons, both SNARF derivatives
      appeared essentially insensitive to changes in [Na+]i. The utility of the
      technique was demonstrated in neurons co-loaded with SBFI and SNARF-5F, which was
      found to have a lower p Ka in situ than carboxy SNARF-1. There were no
      significant differences in the changes in [Na+]i and pHi observed in response
      either to intracellular acid loads imposed by the NH4+ prepulse technique or to
      transient periods of anoxia in neurons single-loaded with SBFI or SNARF-5F or co
      loaded with both probes. The findings support the feasibility of using SBFI in
      conjunction with either carboxy SNARF-1 or SNARF-5F to concurrently and
      accurately measure [Na+]i and pHi.

PMID- 15452717
TI  - Information coding and oscillatory activity in synfire neural networks with and
      without inhibitory coupling.
AB  - When a population spike (pulse-packet) propagates through a feedforward network
      with random excitatory connections, it either evolves to a sustained stable level
      of synchronous activity or fades away (Diesmann et al. in Nature 402:529-533
      1999; Cateau and Fukai Neur Netw 14:675-685 2001). Here I demonstrate that in the
      presence of noise, the probability of the survival of the pulse-packet (or,
      equivalently, the firing rate of output neurons) reflects the intensity of the
      input. Furthermore, inhibitory coupling between layers can result in quasi-
      periodic alternation between several levels of firing activity. These results are
      obtained by analyzing the evolution of pulse-packet activity as a Markov chain.
      For the Markov chain analysis, the output of the chain is a linear mapping of the
      input into a lower-dimensional space, and the eigenvalues and eigenvectors of the
      transition matrix determine the dynamics of the evolution. Synchronous
      propagation of firing activity in successive pools of neurons are simulated in
      networks of integrate-and-fire and compartmental model neurons, and, consistent
      with the discrete Markov process, the activation of each pool is observed to be
      predominantly dependent upon the number of cells that fired in the previous pool.
      Simulation results agree with the numerical solutions of the Markov model. When
      inhibitory coupling between layers are included in the Markov model, some
      eigenvalues become complex numbers, implying oscillatory dynamics. The
      quasiperiodic dynamics is validated with simulation with leaky integrate-and-fire
      neurons. The networks demonstrate different modes of quasiperiodic activity as
      the inhibition or excitation parameters of the network are varied.

PMID- 15452719
TI  - Gender dimorphism influences extracellular matrix expression and regeneration of
      muscular tissue in mdx dystrophic mice.
AB  - Mdx mouse, the animal model of Duchenne muscular dystrophy, lacks dystrophin and
      develops an X-linked recessive inflammatory myopathy characterized by
      degeneration of skeletal muscle fibers and connective tissue replacement. The
      present work aimed to assess whether gender dimorphism in mdx mice would
      influence skeletal muscle pathology at ages corresponding to main histological
      changes in the microenvironment of muscular tissue: myonecrosis, regeneration,
      and fibrosis. At the height of myonecrosis (6 weeks postnatal), skeletal muscles
      of male mdx mice showed increased sarcolemmal permeability, numerous inflammatory
      foci, and marked deposition of the extracellular matrix components (ECM) type I
      collagen and laminin. In contrast, age-matched mdx females showed mild ECM
      deposition, discrete myonecrosis, but increased numbers of regenerating fibers
      expressing the satellite cell marker NCAM. In contrast ovariectomized mdx females
      showed decreased numbers of regenerating fibers. Older (24 and 48 weeks
      postnatal) mdx females showed extensive fibrosis with increased sarcolemmal
      permeability and marked deposition of ECM components than corresponding males.
      These results suggest a role for female hormones in the control of myonecrosis
      probably by promoting regeneration of muscular tissue and mitigating inflammation
      especially at ages under the critical influence of sex hormones.

PMID- 15452720
TI  - Lanreotide treatment in a patient with interferon-associated Graves'
      ophthalmopathy.
AB  - BACKGROUND: We report a case of Graves' ophthalmopathy (GO) developed after the
      administration of interferon-alpha for chronic hepatitis C. METHODS: The GO was
      treated with lanreotide. RESULTS: A 47-year-old female patient presented with
      euthyroid GO with spontaneous retrobulbar pain, eyelid edema, conjunctival
      injection and eyelid retraction of the right eye and conjunctival injection of
      the left eye 6 months after administration of interferon-alpha for chronic
      hepatitis C. Orbital computed tomography revealed no involvement of extraorbital
      muscles and no increase in retrobulbar adipose tissue. Only soft tissue was
      involved. These symptoms subsided after 12 weeks of lanreotide treatment, except
      right eyelid retraction, which, however, disappeared later during follow-up.
      CONCLUSION: The use of interferon-alpha may be complicated by GO and lanreotide
      might be considered for GO if patients cannot accept steroid therapy.

PMID- 15452718
TI  - Oxygen free radicals and redox biology of organelles.
AB  - The presence and supposed roles of reactive oxygen species (ROS) were reported in
      literature in a myriad of instances. However, the breadth and depth of their
      involvement in cellular physiology and pathology, as well as their relationship
      to the redox environment can only be guessed from specialized reports. Whatever
      their circumstances of formation or consequences, ROS seem to be conspicuous
      components of intracellular milieu. We sought to verify this assertion, by
      collecting the available evidence derived from the most recent publications in
      the biomedical field. Unlike other reviews with similar objectives, we centered
      our analysis on the subcellular compartments, namely on organelles, grouped
      according to their major functions. Thus, plasma membrane is a major source of
      ROS through NAD(P)H oxidases located on either side. Enzymes of the same class
      displaying low activity, as well as their components, are also present free in
      cytoplasm, regulating the actin cytoskeleton and cell motility. Mitochondria can
      be a major source of ROS, mainly in processes leading to apoptosis. The protein
      synthetic pathway (endoplasmic reticulum and Golgi apparatus), including the
      nucleus, as well as protein turnover, are all exquisitely sensitive to ROS
      related redox conditions. The same applies to the degradation pathways
      represented by lysosomes and peroxisomes. Therefore, ROS cannot be perceived
      anymore as a mere harmful consequence of external factors, or byproducts of
      altered cellular metabolism. This may explain why the indiscriminate use of anti
      oxidants did not produce the expected "beneficial" results in many medical
      applications attempted so far, underlying the need for a deeper apprehension of
      the biological roles of ROS, particularly in the context of the higher cellular
      order of organelles.

PMID- 15452721
TI  - Visual improvement during psychophysical training in an adult amblyopic eye
      following visual loss in the contralateral eye.
AB  - BACKGROUND: Recent publications have demonstrated neural plasticity in adult
      amblyopes subjected to psychophysical training based on perceptual learning. The
      purpose of this case report is to present rarely available prospective data of
      visual acuity development in a strabismic amblyope undergoing psychophysical
      training and pleoptic treatment after loss of function of the non-amblyopic eye.
      METHODS: The design is a prospective, observational and interventional case
      report. Visual acuity was tested monthly, with constant optical correction. The
      60-year-old female patient participated in a psychophysical training implemented
      in our laboratory, and in pleoptic treatment. RESULTS: Slow functional
      improvement of the amblyopic eye was observed during a period of 10 months, both
      in the tests used for training and in visual acuity: single optotypes increased
      by 4 chart lines, crowded optotypes by 2-3 lines. CONCLUSIONS: To our knowledge,
      this is the first report of the new approach of perceptual learning in an adult
      amblyope after loss of vision in the contralateral eye. Our results represent
      further evidence that the visual system of adult amblyopes preserves a certain
      degree of neural plasticity, whether spontaneous or enhanced by training.
      Furthermore, that plasticity in adults is limited, and early diagnosis and
      treatment of amblyopia must remain the primary goal.

PMID- 15452722
TI  - Mutations in the gene coding for guanylate cyclase-activating protein 2 (GUCA1B
      gene) in patients with autosomal dominant retinal dystrophies.
AB  - BACKGROUND: We investigated mutations in the gene coding for guanylate-cyclase
      activating protein 2 (GCAP2), also known as GUCA1B gene, in Japanese patients
      with retinitis pigmentosa (RP) and tried to identify phenotypic characteristics
      associated with mutations in the gene. SUBJECTS AND METHODS: Genomic DNA samples
      from 63 unrelated patients with autosomal dominant retinitis pigmentosa (ADRP)
      and 33 patients with autosomal recessive retinitis pigmentosa (ARRP) were
      screened by single-strand conformational polymorphism analysis followed by direct
      sequencing. Clinical features associated with a mutation were demonstrated by
      visual acuity, visual field testing, fundus photography, and electroretinography.
      RESULTS: A novel transitional mutation converting GGA to AGA at codon 157 (G157R)
      was identified. This mutation has been found in three index patients from three
      independent families. Phenotypic examination of seven members of the three
      families revealed that this mutation was associated with RP with or without
      macular involvement in five members, macular degeneration in one member, and
      asymptomatic normal phenotype in one member. In addition, previously unknown
      polymorphic changes including V29V, Y57Y, T87I, and L180L were identified.
      CONCLUSIONS: A racial difference exists in the spectrum of mutations and/or
      polymorphisms in the GCAP 2 gene between British and Japanese populations. Our
      findings suggest that the mutation in the GCAP 2 gene can cause one form of
      autosomal dominant retinal dystrophy, with variable phenotypic expression and
      incomplete penetrance.

PMID- 15452724
TI  - Bilateral corneal perforation in familial amyloidotic polyneuropathy.
AB  - PURPOSE: We report the progression of bilateral central perforating ulceration in
      the cornea of a patient with familial amyloidotic polyneuropathy (FAP), also
      known as hereditary Portuguese amyloidosis, who received two corneal grafts in an
      interval of 6 years. The pathology of the original host and the grafted cornea is
      described. METHODS: Overall histology and immunolocalization of transthyretin,
      amyloid beta (Abeta), and epithelial and inflammatory markers were performed.
      RESULTS: Corneal sensitivity and tear film were reduced. The grafted but not the
      original tissue contained amyloid deposits with transthyretin immunoreactivity.
      Epithelial and stromal thinning was accentuated in the graft, with epithelial
      dysplasia, hyperproliferation, and parakeratosis. Abundance of basement membrane
      material in hyperproliferative regions suggested recurrent attempts of wound
      healing. Activated keratocytes, ingrowth of vessels, infiltrated inflammatory,
      and immune cells reflect both acute and chronic inflammation. CONCLUSION: Amyloid
      deposits may progressively reduce corneal sensitivity and damage epithelium and
      stroma. Corneal neuropathy, together with impaired tear film, may entail the
      pathology of dry eyes as a bystander effect, contributing to exacerbation of
      epithelial injury, deregulated proliferation, and parakeratosis. Once
      established, both acute and chronic inflammation may sustain progression of the
      corneal pathology.

PMID- 15452725
TI  - The role of perforin-mediated apoptosis in lichen planus lesions.
AB  - Lichen planus is recognized as a T-cell-mediated disease. Histologically, it is
      characterized by the formation of colloid bodies representing apoptotic
      keratinocytes. The apoptotic process mediated by CD8(+) cytotoxic T lymphocytes
      (CTLs) and NK cells mainly involves two distinct pathways: the perforin/granzyme
      pathway and the Fas/FasL pathway. So far, little is known regarding the role of
      perforin-mediated apoptosis in lichen planus. In the present study, the
      expression and distribution of perforin, T and NK cell subsets in the epidermis
      and dermis of lesional and nonlesional lichen planus skin were studied. Skin
      biopsy specimens from lesional and nonlesional skin of ten patients with lichen
      planus and eight healthy persons were analysed by immunohistochemistry.
      Significant accumulation of T cells, particularly of CD4(+) and CD8(+) subsets,
      was found in both epidermis and dermis of lichen planus lesions compared with
      nonlesional and healthy skin. There were no significant differences in the
      incidence of NK cells (CD16(+) and CD56(+)) between lesional, nonlesional and
      healthy skin. Perforin expression was significantly upregulated in the epidermis
      of lichen planus lesions. In conclusion, accumulation of perforin(+) cells in the
      epidermis of lichen planus lesions suggest a potential role of perforin in the
      apoptosis of basal keratinocytes.

PMID- 15452726
TI  - Modulation of endothelial dysfunction and apoptosis: UVA1-mediated skin
      improvement in systemic sclerosis.
AB  - UVA1-mediated effects regarding vascular dysregulation as a primary pathogenetic
      factor of systemic sclerosis skin lesions have so far not been investigated. Pre-
      and posttherapy skin biopsies of four patients were evaluated
      immunohistochemically for angiostatic, angiogenic and angioapoptotic features.
      Immunohistochemistry revealed a partial pretherapy loss of endothelial CD31 and
      CD34 expression accompanied by a posttherapy increase of CD34(+) cells.
      Simultaneously, VEGF and M30 CytoDEATH immunolabeling demonstrated UVA1-induced
      neovascularization and decreased endothelial apoptosis. Our results suggest that
      UVA1 irradiation exerts its positive effects by a modulation of endothelial
      regulation/transformation beside the proposed induction of T cell apoptosis and
      collagenases.

PMID- 15452727
TI  - Abdominal cystic mass in infancy--in utero perforated Meckel's diverticulum?
AB  - Meckel's diverticulum occurs in 2% of the population. Of these, 4% may present as
      intestinal bleeding, intussusception, diverticulitis, volvulus, or perforation at
      any age, including neonates. We describe a 3-month-old baby whose giant Meckel's
      diverticulum had probably perforated in utero, leading to the formation of a
      large intra-abdominal pseudocyst.

PMID- 15452728
TI  - Thickening of the internal anal sphincter in idiopathic constipation in children.
AB  - Thickening of the internal anal sphincter (IAS) is observed in chronic idiopathic
      constipation (IC) and solitary rectal ulcer syndrome (SRUS), where it has been
      correlated with the presence and severity of rectal intussusception.
      Alternatively, thickened IAS may be a feature of the obstructed megarectum in a
      similar way to the hypertrophy of bladder neck seen in dyssynergic bladders. The
      aim of this study was to investigate the significance of thickening of the IAS in
      children with chronic IC and to determine any association between the thickened
      IAS and anorectal manometry findings and patient's symptoms. A total of 144
      children were admitted for investigations and treatment of chronic IC and
      evaluated prospectively between April 2001 and April 2003. IAS thickness was
      measured by endosonography using B&K axial endosonic probe type 1850 with a 10
      MHz rotating transducer. The thickness of IAS was measured at 3, 6, and 9
      o'clock, and the mean value of the three measurements was used for analysis.
      Functional assessment was done by anorectal manometry pressure studies under
      ketamine anaesthesia. A validated symptom score (SS) was used to assess the
      severity of symptoms. The sum of SS ranged between 0 and 65. Spearman's rho two
      tailed test was used to correlate the thickness of IAS with patients' symptoms
      and anorectal manometry findings. Results were expressed as median and range and
      p-value of less than 0.05 was considered significant. Of 144 children, 84 were
      boys, median age 8.1 years (range 3.1-15). Soiling was present in 137 (94%)
      patients, delay in defecation in 132 (91%), and a palpable megarectum on
      abdominal examination in 117 (80%). The median duration of symptoms and duration
      of laxative treatment were 4 years (range 0.3-14.5) and 3.3 years (0.2-13.5),
      respectively. The average severity score for soiling, delay in defecation,
      palpable megarectum, and the total SS were 8 (range 0-10), 5 (0-10), 2 (0-12),
      and 33 (11-51), respectively. The median thickness of IAS was 0.9 mm (range 0.3
      2.8) and the median resting anal sphincter pressure was 54 mmHg (19-107). The
      median amplitudes of rectal and anal sphincter contraction were 3 mmHg (1-25) and
      9 mmHg (1-35), respectively. The thickness of IAS correlated significantly with
      total symptom severity score (r=0.31, p=0.0001), soiling score (r=0.28, p=0.001),
      megarectum score on abdominal palpation (r=0.29, p=0.001), size of megarectum on
      manometry (r=0.36, p=0.0001), amplitude of rectal contraction (r=0.23, p=0.007),
      and age of patient (r=0.55, p=0.0001). There was also a significant correlation
      between the amplitude of rectal and anal sphincter contraction (r=0.32,
      p=0.0001). There was no correlation between thickness of IAS and resting anal
      sphincter pressure and amplitude of anal sphincter contraction on anorectal
      manometry study. A total of 24 children had myectomy of thickened and overactive
      IAS in addition to the medical treatment of their chronic IC. The histology
      examination of myectomy specimen with eosin and haematoxylin staining and
      histochemical acetylcholine esterase staining showed smooth muscle fibres and
      ganglion cells. Thickening of IAS correlates significantly with duration and
      severity of symptoms, size of megarectum, and amplitude of rectal contraction.
      The pathogenesis is secondary to the continuous presence of faeces in the rectum,
      resulting in chronic abnormal stimulus to the IAS, which leads to hypertrophic
      changes in the rectum wall and IAS.

PMID- 15452729
TI  - Uncommon case of a cystic papillary meningioma in an adolescent.
AB  - INTRODUCTION: Meningiomas, especially papillary meningiomas, are rare tumours in
      childhood and adolescence. They are histologically classified as atypical. CASE
      REPORT: We present a 15-year-old girl with a cystic papillary meningioma
      extending from the infratentorial to the supratentorial region extracranially.
      After a two-stage gross total resection combined with fractionated radiotherapy
      of a small residual tumour in the infratemporal fossa, the clinical course was
      stable for at least 4 years. Then a new infratentorial cystic papillary
      meningioma with a histological change in tumour malignancy was recognised within
      only 1 year. DISCUSSION: Besides the rare histology of a cystic papillary
      meningioma in an adolescent, the case is remarkable due to the considerable
      extent of the tumour and the irregular course with rapid regrowth and change into
      malignancy after an initially stable and benign course. For a comparison, the
      current literature is reviewed and discussed with regard to sex and age
      distribution, histopathological features, clinical course and therapeutical
      options.

PMID- 15452730
TI  - Chiari malformation type I associated with familial spastic paraplegia: report of
      a surgically treated case.
AB  - CASE REPORT: We describe the case of a 7-year-old girl with Chiari malformation
      type I (CMI) and concomitant familial spastic paraplegia (FSP), who exhibited
      spastic gait disturbance. She also showed poor results on the standing tolerance
      test using thermography, which evaluates autonomic nerve function. The patient
      was subjected to posterior fossa decompression and cervical 1 (C1) laminectomy
      for CMI based on the result of the standing tolerance test. After the operation
      her gait disturbance and autonomic nerve dysfunction improved. DISCUSSION:
      Although no cases of CMI and concomitant FSP have been reported, due to the fact
      that autonomic nerve dysfunction is one of CMI symptoms but never FSP, the
      diagnosis of autonomic nerve dysfunction of CMI using the standing tolerance test
      played an important role in selecting the surgical procedure for this case.

PMID- 15452732
TI  - A mathematical model for the growth of the abdominal aortic aneurysm.
AB  - We present the first mathematical model to account for the evolution of the
      abdominal aortic aneurysm. The artery is modelled as a two-layered, cylindrical
      membrane using nonlinear elasticity and a physiologically realistic constitutive
      model. It is subject to a constant systolic pressure and a physiological axial
      prestretch. The development of the aneurysm is assumed to be a consequence of the
      remodelling of its material constituents. Microstructural 'recruitment' and fibre
      density variables for the collagen are introduced into the strain energy density
      functions. This enables the remodelling of collagen to be addressed as the
      aneurysm enlarges. An axisymmetric aneurysm, with axisymmetric degradation of
      elastin and linear differential equations for the remodelling of the fibre
      variables, is simulated numerically. Using physiologically determined parameters
      to model the abdominal aorta and realistic remodelling rates for its
      constituents, the predicted dilations of the aneurysm are consistent with those
      observed in vivo. An asymmetric aneurysm with spinal contact is also modelled,
      and the stress distributions are consistent with previous studies.

PMID- 15452731
TI  - Immunotherapy for malignant gliomas: emphasis on strategies of active specific
      immunotherapy using autologous dendritic cells.
AB  - REVIEW: In this review, we discuss immunotherapy for malignant gliomas. EMPHASIS:
      The emphasis is on the novel strategy of active specific immunotherapy using
      dendritic cells as antigen-presenting cells, especially its theoretical concepts
      and advantages, specific requirements, critical issues, pre-clinical and early
      clinical experience. Dendritic cell vaccination is situated in the diversity of
      other immunotherapeutical approaches. FURTHER DISCUSSION: Future directions,
      challenges, and drawbacks will be discussed.

PMID- 15452733
TI  - Willingness to pay for dental fear treatment. Is supplying dental fear treatment
      socially beneficial?
AB  - The aim of this paper is to discuss the social desirability of supplying dental
      fear treatment in addition to dental treatment using the results from a treatment
      programme for patients with severe dental fear. The programme consisted of three
      different dental fear treatments: Cognitive therapy, applied relaxation and
      nitrous oxide sedation, in addition to dental treatment. To evaluate the effects
      of uncertainty on the patients' benefits from the programme, we elicited their
      willingness to pay, both before and after receiving treatment, since we expected
      patients to be uncertain about the outcome of the dental fear treatment. We found
      that the social desirability of the treatment was very sensitive to uncertainty.
      While only 24% of the patients were willing to pay the actual cost of the
      treatment before attending, 71% were willing to pay afterwards. This implies that
      many patients who would benefit from the treatment ex post are not willing to pay
      the cost of the treatment ex ante, and will thus not receive any treatment unless
      it is subsidized.

PMID- 15452734
TI  - Discrete choice experiments in health economics. For better or for worse?
AB  - One method that is increasingly being used in health economics to elicit stated
      preferences concerning health matters is the discrete choice experiment (DCE).
      This editorial explores four sets of issues facing researchers who wish to employ
      DCE techniques: (a) normative issues about how data from DCE studies might be
      used to inform policy, (b) psychological issues concerning the meaningfulness of
      the data generated, (d) technical issues relating to how the data are generated
      and (d) issues relating to the generalisability of the data from DCE studies.
      Given current uncertainties surrounding these issues, it is our view that more
      caution and greater circumspection towards DCE is appropriate at this stage.

PMID- 15452735
TI  - A method for cross-sector priority setting. Gaps and hypotheses in malaria
      research: Tanzania.
AB  - This study proposes a new priority setting method for identifying critical
      information gaps in a multisector system. The method uses graph-theoretical
      concepts and principles of systems theory in characterizing the underlying
      information structure of the system. Its application is illustrated in the
      context of malaria control in Tanzania, drawing on the findings of a workshop
      held in October 2003 in Dar es Salaam. The workshop identified two critical
      pathways, EVHA and EVHPA, which warrant better understanding. The first suggests
      that the malaria research should generate information on the effects of
      environmental changes (E) on vector ecology (V) and then on the effects of V on
      human health (H) and then on the effects of H on agriculture (A). Interpreted
      likewise, the second pathway additionally points to the need for information on
      the effects of socioeconomic conditions (P) on A.

PMID- 15452736
TI  - A note on the impact of hours worked on mortality in OECD countries.
AB  - We investigate whether an increase in hours worked per employed person raises the
      total mortality rate in a sample of 23 OECD countries. We build on earlier
      research but extend the analysis by introducing the number of hours worked per
      employed as an additional regressor. Contrary to our expectations, we found that
      an increase in the number of hours worked actually has significantly negative
      effect on mortality rate, even controlling for income. Although one explanation
      may be that fluctuations in hours of work is in fact in this setting more a
      measure of the capacity use rate of the economy than a measure of how stressful
      work is for individuals who are working, more research on the topic is needed to
      find a plausible explanation for the observed phenomenon.

PMID- 15452737
TI  - The high cost of medicines in Ireland. Is it time to change the pricing
      mechanism?
AB  - This study compared the prices of prescription medicines in Ireland to those in
      other countries to determine potential cost savings on the largest community drug
      scheme if an alternative pricing mechanism were adopted. The analysis covered a
      sample of 39 drugs (44.8% of the total ingredient cost) selected from the top 70
      drugs in order of total ingredient cost. Potential cost savings ranged from Euro
      20.73 million if a Danish price were adopted, to Euro 16.23 million for the
      average European price, to Euro 6.82 million for the UK price. The estimated
      savings were statistically significant for the Danish and average European price
      but not for the UK price. This study demonstrates the high ex-wholesale price of
      prescription medications in Ireland.

PMID- 15452738
TI  - Examining the quality of health economic analyses submitted to the Pharmaceutical
      Benefits Board in Sweden. The first year.
AB  - This study assessed the quality of health economic documentation submitted to the
      Pharmaceutical Benefits Board (PBB) in Sweden. Two different instruments were
      used in the evaluation: the PBB checklist, which was constructed by the authors
      from the PBB guidelines for health economic evaluations, and the QHES, a
      validated quality assessment instrument. Some areas that seem especially
      problematic, or where the quality was particularly low are identified and
      discussed. Also, we present the cost per quality-adjusted life-year that the
      companies have presented and how this related to the PBBs decisions.

PMID- 15452739
TI  - Approval times and the safety of new pharmaceuticals.
AB  - This study examined the relationship between the approval times for new
      pharmaceuticals and the number of adverse drug reactions reported to the Swedish
      Medical Products Agency. Yearly time-series data concerning the number of adverse
      drug reactions, as well as data concerning prices and quantities sold for 25
      pharmaceutical substances during the period 1972-1996 were used. The results show
      that shorter approval times are associated with more adverse drug reactions, but
      also that the effects are quite small.

PMID- 15452740
TI  - Direct medical costs of monitoring and treating patients with Takayasu arteritis
      in Italy.
AB  - The study provides the first overall estimate of the costs of Takayasu arteritis
      (TA) monitoring and treatment in Italy and highlights the differences in cost
      components across defined subgroups of patients. We estimated resource
      consumption and direct costs from the Italian National Health Service
      perspective. We conducted a multicenter, prospective study in 12 medical
      departments. All the 67 patients recruited met the American College of
      Rheumatology 1990 criteria for the classification of TA and were followed up for
      1 year. For the purpose of analysis they were divided into two groups: "active
      TA" (patients who had taken at least one drug specific for TA treatment, i.e.,
      corticosteroids and/or cytotoxics), and "inactive TA" (all the remaining
      patients). The average cost per year was Euro 4,079. Patients with active TA
      (Euro 5,055) had a significantly higher mean cost per year than those with
      inactive TA (Euro 1,328). In particular, significant differences were found for
      costs in general practitioner consultations, laboratory tests, and hospital
      admissions. These findings suggest that patients not only experience more
      complications requiring hospital admissions but also see general practitioners
      more often during the active stage of the disease, presumably in order to obtain
      a prescription for laboratory tests.

PMID- 15452741
TI  - Health care provider payment mechanisms in the new EU members of Central Europe
      and the Baltic states. Current reforms, incentives, and challenges.

PMID- 15452742
TI  - Modeling the economic burden of diseases imputable to stress at work.
AB  - This study evaluated the costs of work-related stress in France. Three illnesses-
      cardiovascular diseases, depression, musculoskeletal diseases and back pain--that
      may result from exposure to stress are identified and the proportions of cases
      attributable to the risk factor are calculated from epidemiological studies. Two
      methodological hypotheses allow us to provide complementary evaluations of the
      social cost of occupational stress and raise the ethical questions inherent in
      the choice of methodology. For the year 2000 our model shows that of a working
      population of 23.53 million in France some 310,000-393,400 persons (1.3-1.7%)
      were affected by illnesses attributable to work-related stress, and that 2,300
      3,600 persons died as a result of their illness. Work-related stress costs
      society between Euro 1,167 million and Euro 1,975 million in France, or 14.4
      24.2% of the total spending of social security occupational illnesses and work
      injuries branch.

PMID- 15452743
TI  - Consumer preferences in social health insurance.
AB  - Allowing consumers greater choice of health plans is believed to be the key to
      high quality and low costs in social health insurance. This study investigates
      consumer preferences (361 persons, response rate 43%) for hypothetical health
      plans which differed in 12 characteristics (premium, deductibles, no-claim
      discount, extension of insurance and financial services, red tape involved,
      medical help-desk, choice of family physicians and hospitals, dental benefits,
      physical therapy benefits, benefits for prescription drugs and homeopathy). In
      90% the health plan with the most attractive characteristics was preferred,
      indicating a predominantly rational kind of choice. The most decisive
      characteristics for preference were: complete dental benefits, followed by zero
      deductibles, and free choice of hospitals.

PMID- 15452744
TI  - The risk-adjusted vision beyond casemix (DRG) funding in Australia. International
      lessons in high complexity and capitation.
AB  - Hospitals throughout the world using funding based on diagnosis-related groups
      (DRG) have incurred substantial budgetary deficits, despite high efficiency. We
      identify the limitations of DRG funding that lack risk (severity) adjustment for
      State-wide referral services. Methods to risk adjust DRGs are instructive. The
      average price in casemix funding in the Australian State of Victoria is policy
      based, not benchmarked. Average cost weights are too low for high-complexity DRGs
      relating to State-wide referral services such as heart and lung transplantation
      and trauma. Risk-adjusted specified grants (RASG) are required for five high
      complexity respiratory, cardiology and stroke DRGs incurring annual deficits of
      $3.6 million due to high casemix complexity and government under-funding despite
      high efficiency. Five stepwise linear regressions for each DRG excluded non
      significant variables and assessed heteroskedasticity and multicollinearlity.
      Cost per patient was the dependent variable. Significant independent variables
      were age, length-of-stay outliers, number of disease types, diagnoses, procedures
      and emergency status. Diagnosis and procedure severity markers were identified.
      The methodology and the work of the State-wide Risk Adjustment Working Group can
      facilitate risk adjustment of DRGs State-wide and for Treasury negotiations for
      expenditure growth. The Alfred Hospital previously negotiated RASG of $14 million
      over 5 years for three trauma and chronic DRGs. Some chronic diseases require
      risk-adjusted capitation funding models for Australian Health Maintenance
      Organizations as an alternative to casemix funding. The use of Diagnostic Cost
      Groups can facilitate State and Federal government reform via new population
      based risk adjusted funding models that measure health need.

PMID- 15452745
TI  - Pricing of pharmaceuticals. Assessing the pricing potential by a pricing matrix
      model.
AB  - Pricing and reimbursement of new pharmaceuticals have been based until recently
      on the traditional clinical trial outcomes (efficacy, safety, and quality
      parameters) used for registration. Now we can distinguish various additional data
      requirements which relate to the use of the drug in real daily practice. The most
      important new data requirements are effectiveness, cost-effectiveness, and
      budgetary impact. A main question is how much the impact is of the various types
      of data in the pricing and reimbursement process. The objective of this
      contribution is to present a method for quantifying this type of uncertainty in
      order to develop a more solid pricing and reimbursement strategy for a new
      innovative drug. The concepts are illustrated for a new hypothetical
      antidepressant drug in The Netherlands. This method is based on the analytic
      hierarchy process (AHP) concept which measures decision makers' preferences for
      the critical success factors. This study shows that the AHP concept may be
      applied to the pricing and reimbursement environment. The method may be used to
      assess the pricing potential of a new drug, considering the various data
      requirements in the reimbursement process.

PMID- 15452747
TI  - Genetic screening, health care and the insurance industry. Should genetic
      information be made available to insurers?
AB  - The potential use of genetic tests in insurance has raised concerns about
      discrimination and individuals losing access to health care either because of
      refusals to test for treatable diseases, or because test-positives cannot afford
      premiums. Governments have so far largely sought to restrict the use of genetic
      information by insurance companies. To date the number of tests available with
      significant actuarial value is limited. However, this is likely to change,
      raising more clearly the question as to whether the social costs of adverse
      selection outweigh the social costs of individuals not accessing health care for
      fear of the consequences of test information being used in insurance markets. In
      this contribution we set out the policy context and model the potential trade
      offs between the losses faced by insurers from adverse selection by insurees
      (which will increase premiums reducing consumer welfare) and the detrimental
      health effects that may result from persons refusing to undergo tests that could
      identify treatable health conditions. It argues that the optimal public policy on
      genetic testing should reflect overall societal benefit, taking account of these
      trade-offs. Based on our model, the factors that influence the outcome include:
      the size of and value attached to the health gains from treatment; deterrent
      effects of a disclosure requirement on testing for health reasons; incidence of
      the disease; propensity of test-positives to adverse select; policy value adverse
      selectors buy in a non-disclosure environment; and price elasticity of demand for
      insurance. Our illustrative model can be used as a benchmark for developing other
      scenarios or incorporating real data in order to address the impact of different
      policies on disclosure and requirement to test.

PMID- 15452748
TI  - Price-cost margin in the pharmaceutical industry. Empirical evidence from
      Finland.
AB  - This contribution estimates the price-cost margin in the Finnish pharmaceutical
      industry. The estimation is based on the method developed by Hall who shows that
      under constant returns to scale total factor productivity growth depends on the
      growth of output-capital ratio if the market is imperfectly competitive.
      Measurement of the price-cost margin is based on this theoretical result. We
      utilize data on the Finnish pharmaceutical industry. The data cover the years
      1975-1999 and include information on output, labor hours, and capital stock. The
      results show that the estimated price-cost margin is in the range 0.59-0.67,
      which is close to the estimates obtained in the United States market.

PMID- 15452749
TI  - Model for simulation of HIV/AIDS and cost-effectiveness of preventing non
      tuberculous mycobacterial (MAC)-disease.
AB  - Because most HIV-infected patients die of diseases caused by opportunistic
      pathogens, the prevention of these infections is an important clinical issue.
      Cost-containment in the healthcare system is a subject of high priority in public
      debate. Methods to determine cost-effectiveness of different therapeutic
      strategies are therefore needed to obtain valid data as the basis for decisions
      on cost reduction without a decrease in the quality of care. A disease state
      transition model based on a Markov process was developed to simulate the natural
      history of HIV infection and the acquired immunodeficiency syndrome (AIDS). Using
      this model survival time and treatment costs for every patient can be estimated
      and the results of alternative medications compared. We determined the cost
      effectiveness (per life-year saved, LYS) of different strategies for prevention
      of Mycobacterium avium complex infections in AIDS patients whose treatment
      regimens include protease inhibitors. The cost-effectiveness ratios for treatment
      strategies vary from 13,510 euro to 46,152 euro per LYS without protease
      inhibitors and from 22,309 euro to 51,336 euro with protease inhibitors. When
      azithromycin, clarithromycin, and rifabutin were compared, azithromycin was the
      most cost-effective medication for preventing M. avium complex. The results were
      stable against a wide range of parameter variations concerning costs and
      incidence rates.

PMID- 15452750
TI  - Potential cost-effectiveness of a family-based program in mild Alzheimer's
      disease patients.
AB  - Alzheimer's disease (AD) is a chronic and progressive neurodegenerative disease
      characterized by a progressive deterioration in cognitive functions. AD will have
      a major impact on public health in the coming decades. The objective of this
      study was to evaluate the potential cost-effectiveness of a cognitive-behavioral
      family intervention (CBFI) program in patients with mild Alzheimer's disease in
      Finland. A second-order Monte Carlo technique was used to simulate the
      effectiveness of the intervention in AD patients and their informal caregivers
      over the course of 5 years. A Bayesian approach was applied to answer the
      question: how likely is it that the CBFI program is cost-effective? Based on
      existing information, the incremental net health benefit of the CBFI program is
      positive with over 0.9 probability, which indicates that the CBFI program has the
      highest probability of being optimal by providing greater net benefits than
      current practice. Furthermore, changes in the health-related quality of life of
      the caregivers were insensitive to AD patients' disease stage and settings of
      care. From the methodological point of view, the acceptability curve with a
      Bayesian approach provides a flexible way to characterize uncertainty surrounding
      cost-effectiveness parameters.

PMID- 15452751
TI  - Economic evaluation of a combined DTPa, hepatitis B, polio, Hib vaccine.
      Potential impact of the introduction of Infanrix-Hexa in the French childhood
      immunisation schedule.
AB  - A new hexavalent combination vaccine, Infanrix-HEXA, including a recombinant
      hepatitis B vaccine in addition to the vaccines for diphtheria, tetanus,
      pertussis, poliomyelitis, and Haemophilus influenzae type B, has recently become
      available in France. The objectives of this study were to: (1) estimate the break
      even price of Infanrix-Hexa for the National Sickness Fund; (2) evaluate its
      potential impact on vaccine coverage for hepatitis B and the corresponding budget
      impact. The public price of Infanrix-HEXA associated with a break-even point
      would be 53.77 euro. Our analyses suggested that other estimates based on a
      societal perspective including opportunity and indirect costs remained close to
      this value. The annual additional reimbursed cost of protecting an infant against
      the risk of hepatitis B would be 28.20 euro per child, or about 21 million euro
      for an annual cohort of 760,000 births (total cost, 35 million euro). The number
      of infants protected against hepatitis B could increase from 230,000 in the
      current situation to about 600,000.

PMID- 15452752
TI  - An empirical analysis of the demand for physician services across the European
      Union.
AB  - This paper presents parameter estimates for physician service equations using the
      "European Community Household Panel" for 12 countries covering the period 1994
      1996. The focus is on two specific points: (1) the identification of behavioural
      similarities and differences in the demand for health services across the 12
      countries; (2) the variability in demand for health services represented through
      a joint model for all countries. We found that there are significant differences
      among countries, although there are also similarities in the effect of variables
      such as health stock, labour situation or family structure. An important fraction
      of the variability in the demand for health services across countries could be
      explained by differences in age, income and the role of general practitioners as
      gatekeepers in the public health system. We found some evidence of induced demand
      in the decision to visit a specialist and in the number of such visits.

PMID- 15452753
TI  - Economic growth, longevity and the epidemiological transition.
AB  - This paper integrates investments in health to a standard growth model where
      physical and human capital investments are the combined engines of growth. It
      shows the existence of two distinct health regimes separated by an
      "epidemiological transition." The various patterns of this transition identified
      in the epidemiological literature can be mapped into the model. The model also
      leads to the important hypothesis that the epidemiological transition may induce
      an economy to switch to a modern growth regime.

PMID- 15452754
TI  - Dynamic competition in pharmaceuticals. Patent expiry, generic penetration, and
      industry structure.
AB  - This paper investigates patterns of industrial dynamics and competition in the
      pharmaceutical industry, with particular reference to the consequences of patent
      expiry in different countries. We focus on the competition at the level of single
      chemical entities, distinguishing between original brands and generic products.
      Quarterly data, spanning from July 1987 to December 1998, on sales of
      pharmaceutical products in four countries (USA, UK, Germany, and France)
      constitute the basis of our analysis. All the products containing major molecules
      whose patent expiration date lies between 1986 and 1996 are included in our
      sample. We show how diffusion of generics is linked to the characteristics of the
      market and investigate how price dynamics of original products are affected by
      generic competition. Our empirical investigation shows that the dynamics of drug
      prices and the competition by generic drugs vary significantly across countries.
      This heterogeneity notwithstanding, a clear distinction seems to emerge. On the
      one hand, systems that rely on market-based competition in pharmaceuticals
      promote a clear distinction between firms that act as innovators and firms that
      act as imitators after patent expiry. Here, original products enjoy premium
      prices and exclusivity profits under patent protection, and face fierce price
      competition after patent expiry. On the other hand, in systems that rely on
      administered prices, penetration by generic drugs tends to be rather limited. Its
      descriptive and preliminary nature notwithstanding, our analysis seems to have
      relevant implications at different levels of generality, especially for Europe.

PMID- 15452755
TI  - The European Network of Health Economic Evaluation Databases (EURO NHEED)
      Project.
AB  - This paper provides a first outline of the European Network of Health Economic
      Evaluation Databases (EURO NHEED) project. The project is funded by the European
      Commission and will implement, in 7 European centres based in France, Germany,
      Italy, The Netherlands, Spain, Sweden and the United Kingdom, databases on the
      economic evaluation of healthcare interventions. The network will be based on two
      existing and well-established resources, namely the UK's NHS Economic Evaluation
      Database (NHS EED), and France's Connaissances et Decision en EConomie de la
      Sante (CODECS) database. EURO NHEED will initially cover 17 European countries
      and will provide its users with bibliographic records, detailing the main
      characteristics of all included studies. In addition, structured abstracts will
      be provided for articles identified as full economic evaluations (cost-benefit,
      cost-effectiveness or cost-utility), which will offer a detailed critique of the
      findings and the methodology used. These databases will be accessible free of
      charge on the Internet. The EURO NHEED project is the first attempt to develop
      such a resource on a multi-national basis. The project will bring together Health
      Economists and Information Scientists from the European Union and beyond and is
      anticipated to facilitate a number of benefits and advances in the field of
      Health Economics. These include harmonisation and increased understanding of the
      theory and methodology of economic evaluation in healthcare, the interpretation
      of the generalisability of studies to target settings, and the influence of
      healthcare system variations among the European countries. The project will
      therefore advance the state of the art in collecting, summarising, critiquing and
      disseminating economic evaluations of healthcare conducted within Europe.

PMID- 15452756
TI  - Economic evaluation of gemcitabine in the treatment of pancreatic cancer in the
      UK. How important is quality of life?

PMID- 15452757
TI  - Pricing and reimbursement of drugs in Ireland.
AB  - Expenditure on healthcare in Ireland, which is mainly derived from taxation, has
      increased considerably in recent years to an estimated 9.2 billion euro in 2003.
      Pharmaceuticals account for approximately 10% of total healthcare expenditure.
      Approximately one-third of patients receive their medications free of charge
      whilst the remaining two-thirds are subject to a co-payment threshold of 78 euro
      per month, i.e. 936 euro per year. The price of medications in Ireland is linked
      to those of five other member states where the price to the wholesaler of any
      medication will not exceed the lesser of the currency-adjusted wholesale price in
      the United Kingdom or the average of wholesale prices in Denmark, France,
      Germany, The Netherlands and the United Kingdom. A price freeze at the
      introduction price has been in existence since 1993. Despite the price freeze,
      expenditure on medicines on the community drugs scheme has increased from 201
      million euro in 1993 to 898 million euro in 2002. The two main factors
      contributing to the increased expenditure on medicines include "product mix", the
      prescribing of new and more expensive medication, and "volume effect" comprising
      growth in the number of prescription items. Changing demographics and the
      extension of the General Medical Services (GMS) Scheme to provide free medicines
      for all those over the age of 70 years have also contributed. Prior to
      reimbursement under the community drugs schemes, a medicine must be included in
      the GMS code book or positive list. A demonstration of cost-effectiveness is not
      a pre-requisite for reimbursement.

PMID- 15452758
TI  - Hospital funding and competition.

PMID- 15452759
TI  - Evaluating the effect of care programs for elderly persons with dementia on
      caregiver's well-being.
AB  - This contribution provides an econometric evaluation of the impact of two
      innovative care programs for elderly persons with dementia (day-care centers and
      group-living) on the well-being of the primary caregiver of patients. For this
      evaluation we use data from a survey conducted in six European countries in 1998.
      The results show that after adjusting for selection bias day-care centers have a
      positive impact for a specific part of the population. They also reveal a
      rationing mechanism in the access to group-living.

PMID- 15452760
TI  - Direct medical costs unequivocally related to diabetes in Italian specialized
      centers.
AB  - This study estimated the resource utilization and direct medical costs in Italian
      diabetes centers (DCs). Hospital admissions for major chronic complications were
      not considered since DCs deliver primary care and follow up only complications
      unequivocally related to diabetes-acute complications and diabetic foot. The
      multicenter, prospective, observational study involving 31 Italian DCs included a
      total of 1,910 patients classified into eight prognostic groups by type of
      diabetes (types 1 and 2), metabolic control (HbA1c >7.5%, HbA1c < or =7.5%) and
      age (< or =60, >60). The average total cost of type 1 diabetes per patient per
      year ranged from 762 euro in group 2 (age < or =60, HbA1c >7.5%) to 1,060 euro in
      group 4 (age >60, HbA1c >7.5%), and that the cost of type 2 diabetes from 423
      euro in group 5 (age < or =60, HbA1c < or =7.5%) to 613 euro in group 8 (age >60,
      HbA1c >7.5%). The study brought to light the wide variability in the single cost
      components across clinically defined groups of patients. The cost of diabetes
      management in the strict sense was significantly affected by the type of diabetes
      and metabolic control.

PMID- 15452761
TI  - Direct medical costs of age-related macular degeneration in Italian hospital
      ophthalmology departments. A multicenter, prospective 1-year study.
AB  - This study calculated the resource utilization and direct medical costs related
      to age-related macular degeneration (AMD). We conducted a multicenter
      observational study in 1999 in seven hospital ophthalmology departments in
      northern and central Italy. A total of 476 patients aged over 50 years with the
      diagnoses were classified into three prognostic groups: (a) drusen (23.7%), (b)
      geographic atrophy (16.4%), and (c) retinal changes associated with choroidal
      neovascularization (CNV) (59.9%). In addition to the costs reimbursed by the
      Italian National Health Service, we estimated also patients' out of pocket
      expenses. The mean cost per patient per year was 383.2 euro; patients with CNV
      were by far the most costly (540.1 euro, vs. 158.1 euro for drusen and 147.9 euro
      for geographic atrophy). Hospital costs and diagnostics were the main cost
      determinants. Services directly paid for by patients (private consultations and
      OTCs) amounted to 46.5 euro for patients with CNV, 50.3 euro for drusen, and 68.8
      euro for geographic atrophy. The major finding of the study was that the presence
      of CNV involved higher expenditure than drusen or geographic atrophy. This
      suggests that the costs of AMD rise significantly with the severity of the
      illness.

PMID- 15452762
TI  - Priority setting for pharmaceuticals. The use of health economic evidence by
      reimbursement and clinical guidance committees.
AB  - Authorities in a number of countries rely increasingly on cost-effectiveness
      analysis to determine reimbursement status or clinical guidance for
      pharmaceuticals. This study compared the use of health economic evidence across
      five reimbursement committees (Australia, Ontario and British Columbia in Canada,
      Finland, and France) and one clinical guidance committee (England and Wales).
      Health economic evidence was found to support decision making, although cost
      effectiveness is less important in some identifiable situations. Since the
      relative importance of cost-effectiveness varies, it will be difficult to
      implement a single explicit threshold. Further research may make patterns of
      decision making, distributional concerns, and the importance of different
      criteria more transparent, which would help to narrow the gap between the theory
      and practice of health economic evaluations. While the use of health economic
      evidence and the outcome of decision making are similar across committees, there
      is presently only limited knowledge to what extent prescribing patterns are
      influenced by decisions.

PMID- 15452763
TI  - Economic valuation of informal care. An overview of methods and applications.
AB  - Informal care makes up a significant part of the total amount of care provided to
      care recipients with chronic and terminal diseases. Still, informal care is often
      neglected in economic evaluations of health care programs. Probably this is
      related to the fact that the costs of informal care are to an important extent
      related to time inputs by relatives and friends of care recipients and time is
      not easy to value. Development of theoretically sound, yet easily applicable
      valuation methods is therefore important since ignoring the costs of informal
      care may lead to undesirable shifts between formal and informal care. Moreover,
      there is increasing evidence that providing informal care may lead to health
      problems for the caregiver, both in terms of morbidity and mortality. Until now
      these health effects have not been incorporated in economic evaluations. More
      attention for the identification and valuation of the full costs and (health)
      effects of informal care for the informal caregiver seems needed therefore. This
      contribution presents a critical evaluation of the available methods to
      incorporate informal care in economic evaluations.

PMID- 15452764
TI  - The burden of varicella in Germany. Potential risks and economic impact.
AB  - Varicella (chickenpox) has traditionally been regarded as a benign, inevitable
      disease of childhood. In Germany information on the clinical and economic impact
      of varicella is limited. This study assessed the health risks and economic burden
      of varicella with a special focus on the relevance of complications as a cost
      driver. We used an age-structured, dynamic infectious disease model for the
      spread of infection in the German population combined with a module modeling the
      course of disease and medical management in the case of infection. Model input
      data were derived mainly from a retrospective epidemiological survey of 1,334
      varicella cases in Germany. This survey included detailed information on
      outpatient care, complications, inpatient treatment, and sick leave. In the base
      case analysis the model predicted approx. 740,000 varicella cases per year. Some
      40,000 experienced complications, of which 5,700 required inpatient care. Total
      annual costs for payers, i.e., sickness funds, was 78 million euro, the largest
      portion of which was due to the significant coverage of work loss costs incurred
      by parents caring for their sick children ("Kinderpflegekrankengeld"). For the
      society total annual costs were 187.5 million euro, 82% of which was indirect.
      Complications account for disproportionate 32% (25%) of cost from the payers'
      (societal) perspective. However, the vast majority of costs are due to
      uncomplicated cases. The burden of varicella in Germany is thus significant, not
      only in terms of morbidity but also from an economic viewpoint. Vaccination
      strategies targeting groups with high risk of complications might fail to reduce
      the considerable burden of varicella substantially. Routine vaccination against
      varicella would be a meaningful measure to reduce the burden of VZV infection in
      Germany.

PMID- 15452765
TI  - Do costs of varicella justify routine infant vaccination? Pharmacoeconomic and
      clinical considerations.

PMID- 15452766
TI  - Economic evaluation and survival analysis of immunoglobulin adsorption in
      patients with idiopathic dilated cardiomyopathy.
AB  - Idiopathic dilated cardiomyopathy (DCM) is a life-threatening heart disease and a
      major reason for heart transplantations. The medical efficacy of immunoadsorption
      (IA) for DCM patients has been demonstrated in initial clinical studies. This
      prospective matched-case control study examined 5-year survival rates, direct
      medical costs, and cost-effectiveness in Germany (n=34) from a health-care system
      perspective. In a cost-effectiveness analysis costs per life year gained were
      calculated. Patients treated with IA showed a greater survival rate: 5-year
      survival rate in the intervention group was 82% vs. 41% in controls. Log rank
      statistics after Kaplan-Meier analysis of cumulated survival probability were
      highly significant. Initial intervention costs for IA were found to be 28,400
      euro per patient treated. Direct medical costs for a 5-year follow-up were
      128,600 euro per patient treated with IA and 75,500 euro in controls. Considering
      only the actual survival time we calculated annual treatment costs of 24,900 euro
      in the IA group and 28,900 euro in controls. The cost-effectiveness ratio
      expressed in costs per life year gained was 34,400 euro. This is the first
      controlled study to perform 5-year survival analysis and economic evaluation of
      this new emerging technology for patients with DCM. Although high initial
      treatment costs for IA are incurred, the significantly better survival rates lead
      to reasonable costs per live year gained.

PMID- 15452767
TI  - Comparison of estimated medical costs among patients who are defined as having
      rheumatoid arthritis using three different standards.
AB  - Accurate estimation of medical care costs raises a host of challenging issues. We
      examined whether pure administrative claims data without clinical validation of
      diagnosis allow reasonable estimation of disease-related costs in rheumatoid
      arthritis (RA). Three patient groups were examined: patients with clinically
      confirmed RA (group A, n=338), patients with likely RA (administrative claims
      data reported the diagnosis of RA and patients were treated with disease
      modifying antirheumatic drugs, DMARDs; group B, n=303), and patients with
      possible RA (same as group B but patients had no DMARD treatment; group C,
      n=685). The payer's perspective was taken for this analysis. Only direct costs
      were included in the analysis. Cost data and data for several covariates were
      obtained from a major German statutory health insurance plan, the AOK
      Niedersachsen. A patient-per-patient microcosting approach was performed. A
      repeated measures, fixed effects model was applied to examine differences between
      the three study groups. Mean+/-SEM annual RA-related direct costs were euro
      2,017+/-183 per patient-year in group A, euro 1,763+/-192 in group B, and euro
      805+/-58 in group C. Outpatient (inpatient) costs were euro 1,636 (328) in group
      A, euro 1344 (340) in group B, and euro 546 (136) in group C. DMARD costs were by
      far the single most important cost driver in groups A and B. The difference in
      total RA-related direct cost between groups A and B was not significant whereas
      the differences between groups A and C (group B and C respectively), were
      significant. Pure administrative claims data allowed for an accurate estimate of
      disease-related costs in RA patients that received DMARD therapy. However, the
      high number of patients for whom administrative claims data listed the diagnosis
      RA, but no DMARD treatment was given poses a challenge for further research.

PMID- 15452768
TI  - Economic burden of head and neck cancer. A literature review.
AB  - This literature review presents the economics of head and neck cancer (HNC), the
      world's sixth most common neoplasm. HNC economics is complicated by the
      involvement of multiple body sites, multiple medical specialties, and multiple
      treatment modalities. Economic analyses of HNC published in English between 1990
      and 2002 were identified from electronic data sources. Additional studies were
      identified manually from bibliographies of retrieved articles. Study
      characteristics and findings were analyzed. We identified 51 studies that
      reported original cost data. Most were cost-identification or cost-comparison
      studies; only one evaluated cost-effectiveness. Few assessed the overall economic
      burden of HNC or cost effectiveness of current treatments, thus making
      appropriate comparisons impossible. Systematic measurement of the cost of HNC and
      its treatment in existing practice settings would be valuable. Inclusion of
      economic components in clinical trials and the conduct of retrospective or
      prospective observational studies, such as patient registries, would yield
      important new information.

PMID- 15452769
TI  - Chained time trade-off and standard gamble methods. Applications in oesophageal
      cancer.
AB  - It may be difficult to value palliative health states using health state
      valuation methods such as the time trade-off (TTO) and standard gamble (SG) where
      health states are traditionally valued relative to perfect/good health and death.
      Chained methods have been developed to help in this context. However, few studies
      have compared the values produced by chained TTO and SG methods. To address this
      issue, a study was conducted to measure the health state values associated with
      oesophageal cancer using chained TTO and SG techniques. The methods were found to
      be acceptable amongst the sample respondents, who had previously been treated for
      oesophageal cancer. There were no significant differences between the health
      state values produced by the TTO and the SG methods. Within each method, however,
      there were significant differences between the health states valued. It is
      concluded that the use of health state valuation techniques such as the TTO and
      SG is feasible amongst people with a history of oesophageal cancer.

PMID- 15452770
TI  - Comparative diagnostic performance of two commercial rapid tests for malaria in a
      non-endemic area.
AB  - In the study reported here, the diagnostic performance of two new rapid tests for
      the diagnosis of malaria was evaluated in symptomatic patients in a non-endemic
      area. Of 557 consecutive patients, 109 (19.6%) had documented malaria. For the
      NOW ICT MALARIA P.f./P.v. (Binax, Portland, ME, USA) and OptiMAL IT (Diamed,
      Cressier, Switzerland) tests, respectively, sensitivity values were 96.3% and
      79.8% (P-value, 0.0001), and specificity values were 98.8% and 98.4%. The NOW ICT
      test did not detect two of 80 Plasmodium falciparum infections, and it generated
      false-positive results for five patients. The OptiMAL IT test failed to detect
      ten of the P. falciparum infections, and it generated seven false-positive
      results. The results suggest that these rapid diagnostic tests for malaria may be
      useful, but they cannot replace microscopic examination of blood films.

PMID- 15452775
TI  - A theoretical study of myoglobin working as a nitric oxide scavenger.
AB  - The mechanism for the reaction between nitric oxide (NO) and O(2) bound to the
      heme iron of myoglobin (Mb), including the following isomerization to nitrate,
      has been investigated using hybrid density functional theory (B3LYP). Myoglobin
      working as a NO scavenger could be of importance, since NO reversibly inhibits
      the terminal enzyme in the respiration chain, cytochrome c oxidase. The
      concentration of NO in the cell will thus affect the respiration and thereby the
      synthesis of ATP. The calculations show that the reaction between NO and the heme
      bound O(2) gives a peroxynitrite intermediate whose O-O bond undergoes a
      homolytic cleavage, forming a NO(2) radical and myoglobin in the oxo-ferryl
      state. The NO(2) radical then recombines with the oxo-ferryl, forming heme-bound
      nitrate. Nine different models have been used in the present study to examine the
      effect on the reaction both by the presence and the protonation state of the
      distal His64, and by the surroundings of the proximal His93. The barriers going
      from the oxy-Mb and nitric oxide reactant to the peroxynitrite intermediate and
      further to the oxo-ferryl and NO(2) radical are around 10 and 7 kcal/mol,
      respectively. Forming the product, nitrate bound to the heme iron has a barrier
      of less than approximately 7 kcal/mol. The overall reaction going from a free
      nitric oxide and oxy-Mb to the heme bound nitrate is exergonic by more than 30
      kcal/mol.

PMID- 15452776
TI  - IR and Raman study on the interactions of the 5'-GMP and 5'-CMP phosphate groups
      with Mg(II), Ca(II), Sr(II), Ba(II), Cr(III), Co(II), Cu(II), Zn(II), Cd(II),
      Al(III) and Ga(III).
AB  - The chief motive behind this research is the interest provoked by the presence of
      metal ions as necessary stabilizers of the negative charges of phosphate groups
      in nucleic acids. The effect that the presence of different metal ions produces
      on the band principally assigned to the nu(s) PO(3)(2-) mode has been studied
      using FT-IR and FT-Raman spectroscopy. The results obtained reveal the diagnostic
      capacity of these techniques in determining the type of metal ion interaction
      with respect to the mononucleotides that form DNA and RNA, providing a tool for
      improving the knowledge of the stabilizing or destabilizing effects of these ions
      on such macromolecules. The metal complexes of the ribonucleotides 5'-CMP and 5'
      GMP with Mg(II), Ca(II), Sr(II), Ba(II), Cr(III), Co(II), Cu(II), Zn(II), Cd(II),
      Al(III) and Ga(III) were obtained in this study. After studying and analyzing the
      IR and Raman spectra of all these complexes and comparing them with the spectra
      of the corresponding disodium salts, it was verified that, independently of the
      type of nucleotide involved, the presence of the metal in the vicinity of the
      phosphate group produces an alteration in the aforementioned nu(s) PO(3)(2-)
      band. This effect is related to the type of interaction that the phosphate group
      has with the metal. Three components are observed: (1) one near 983-975 cm(-1)
      (detectable in IR and Raman), associated with phosphate groups in an
      electrostatic type of interaction with the metal ion, separated by two or more
      water molecules; (2) another near 989-985 cm(-1) (only in IR), associated with
      phosphate groups in indirect interaction through the water molecules of the
      coordination sphere of the metal ions; and (3) the IR and Raman bands near 1014
      1001 cm(-1), which represent phosphate groups directly bonded to the metal ion.
      These results are supported by the behavior of 5'-CMP in aqueous solution in the
      presence of Mg(II) ions.

PMID- 15452778
TI  - Endoscopic diagnosis and treatment of upper gastrointestinal tumors.

PMID- 15452777
TI  - Solution structure of T4moC, the Rieske ferredoxin component of the toluene 4
      monooxygenase complex.
AB  - Toluene 4-monooxygenase, a four-protein complex from Pseudomonas mendocina KR1,
      catalyzes the NADH- and O(2)-dependent hydroxylation of toluene to form p-cresol.
      The solution structure of the 112-amino-acid Rieske ferredoxin component, T4moC,
      was determined from 2D and 3D (1)H, (13)C, and (15)N NMR data. The structural
      model was refined through simulated annealing by molecular dynamics in torsion
      angle space with input from 1650 experimental restraints, including 1264 inter
      proton distance restraints obtained from NOEs, 247 non-redundant intra-residue
      NOEs, 26 hydrogen bond restraints, and 113 dihedral angle ( phi, psi) restraints.
      The 20 calculated conformers that best satisfied the input restraints were
      submitted to refinement in explicit solvent to improve the stereochemical
      quality. With exclusion of ill-defined N- and C-terminal segments (Ser2; His111
      Ser112) and residues near to the [2Fe-2S] cluster, the atomic root mean square
      deviation for the 20 conformers with respect to the mean coordinates was 1.09 A
      for the backbone and 1.60 A for all non-hydrogen atoms. The T4moC structure
      consists of 10 beta-strands arranged in the three anti-parallel beta-sheet
      topology observed in all Rieske [2Fe-2S] domain proteins. The S(gamma) of Cys45
      and Cys64 and the N(delta1) of His47 and His67 provide the ligands to the [2Fe
      2S] cluster of T4moC. (1)H-(15)N HSQC measurements show that both His47
      N(epsilon2) and His67-N(epsilon2) are protonated at the pH of the NMR
      experiments. Comparisons are made between the present NMR structure, previous
      paramagnetic NMR studies of T4moC, and the X-ray structures of other members of
      the Rieske protein family.

PMID- 15452779
TI  - Endoscopic retrograde cholangiopancreatography.

PMID- 15452780
TI  - Detachable snare versus epinephrine injection in the prevention of
      postpolypectomy bleeding: a randomized and controlled study.
AB  - BACKGROUND AND STUDY AIMS: Several endoscopic techniques have been developed to
      prevent bleeding after the removal of large pedunculated polyps. PATIENTS AND
      METHODS: From January 1995 to December 2002, 488 consecutive patients with
      pedunculated colorectal polyps, the heads of which were larger than 10 mm in
      diameter, were randomly assigned to three groups. In group A (163 patients),
      detachable snares were placed at the base of the stalk and standard snares were
      then used for polypectomy. In group B (161 patients), the polyp stalk was
      injected with a 0.01 % epinephrine solution before conventional snare
      polypectomy. Group C (a control group including 164 patients) underwent
      conventional snare polypectomy without preventive measures. Early (< 24 h) and
      late (> 24 h - 30 days) bleeding complications were assessed. Each group was
      divided into two subgroups relative to the polyp size (polyps 1.0 - 1.9 cm and
      polyps > or = 2 cm). RESULTS: Overall bleeding complications occurred after 4.3 %
      of the polypectomies. Bleeding was successfully controlled in all patients, and
      no blood transfusions were required. There were three cases of bleeding in group
      A (1.8 %), five in group B (3.1 %), and 13 in group C (7.9 %). Early bleeding was
      more frequent than late bleeding (15 vs. six patients). In polyps > or = 2 cm
      (207 patients), postpolypectomy bleeding occurred in 14 patients (6.7 %): two
      (2.7 %) in the detachable snare group, two (2.9 %) in the epinephrine injection
      group, and 10 (15.1 %) in the control group. CONCLUSIONS: These results show that
      polypectomy of large pedunculated polyps is associated with a higher incidence of
      bleeding. Particularly in polyps larger than 2 cm, preventive measures can
      significantly reduce bleeding complications after polypectomy. This can be
      achieved with similar efficacy either by placing Endoloops or by injecting
      epinephrine.

PMID- 15452781
TI  - Multicenter retrospective evaluation of capsule endoscopy in clinical routine.
AB  - BACKGROUND AND STUDY AIMS: The small bowel is anatomically difficult to examine;
      disease conditions are rarely located in it, but can be serious. Neither
      conventional radiography nor push enteroscopy has sufficient sensitivity and
      specificity to detect distinct lesions. Wireless capsule endoscopy can
      theoretically allow imaging of the entire small bowel, with only minimal
      discomfort for the patient. PATIENTS AND METHODS: Between November 2001 and May
      2003, 191 patients received 195 capsules. Data were collected retrospectively
      from consecutive patients in three centers. The indications for capsule endoscopy
      were obscure or occult bleeding, suspected Crohn's disease, or other reasons in
      151, 25, and 15 patients, respectively. The clinical outcome after 6 months was
      evaluated on the basis of interviews with patients or relatives. RESULTS:
      Visualization of the entire small bowel was adequate in 78.4 % of the
      examinations. The colon was not reached in 16.9 % of cases, and there were minor
      technical problems in 4.6 %. Relevant pathological findings were identified in
      56.2 % of 151 patients with obscure bleeding or iron-deficiency anemia (64 % of
      whom received blood transfusions). The most common findings were angiodysplasia
      in 39.7 % of cases and ulcers of the small bowel in 7.3 %. In addition,
      individual cases of tumors and parasitic worms were detected. Seven of the 25
      patients with suspected Crohn's disease (28 %) had the disease confirmed. Three
      of five patients with polyposis syndrome of the colon were found to have polyps
      in the small bowel. CONCLUSIONS: Wireless capsule endoscopy can be recommended as
      part of the routine work-up in patients with obscure bleeding or iron-deficiency
      anemia. In patients with Crohn's disease, the method may be helpful in
      establishing or ruling out the diagnosis.

PMID- 15452782
TI  - The value of capsule endoscopy in pediatric patients with a suspicion of Crohn's
      disease.
AB  - BACKGROUND AND STUDY AIMS: The aim of this study was to assess the safety and
      usefulness of capsule endoscopy (CE) in pediatric patients with a suspicion of
      Crohn's disease. PATIENTS AND METHODS: CE was used in 12 patients (four girls,
      eight boys; age 12-16; weight range 43-87 kg). The indication was a clinical
      suspicion of Crohn's disease not confirmed with traditional methods. Gastroscopy,
      colonoscopy, and small-bowel follow-through examinations were carried out in all
      of the patients, without any diagnostic findings. Ileoscopy was possible in 50 %
      of the patients, and the ileal mucosa and biopsies were normal in all cases.
      RESULTS: The capsule was easily swallowed by all of the patients. They all
      excreted the capsule normally, and no complications were observed in any case. CE
      identified lesions suggestive of Crohn's disease in seven of the 12 (58.3 %), and
      the majority of the lesions were in the ileum. CONCLUSIONS: CE is safe in
      pediatric patients over 12 years of age. The procedure appears to be a very
      useful diagnostic tool in children with Crohn's disease.

PMID- 15452783
TI  - Missed diagnoses in patients with upper gastrointestinal cancers.
AB  - BACKGROUND AND STUDY AIMS: A few studies have been published on cancers missed at
      previous endoscopy, but detailed analyses of the causes for failure were lacking.
      The aims of our study were to determine the incidence of and causes for failure
      to detect oesophageal and gastric cancers after referral of patients to a
      surgical endoscopy unit. PATIENTS AND METHODS: Out of a consecutive series of 305
      patients diagnosed with oesophageal and gastric cancers, we retrospectively
      identified patients who had undergone an endoscopy within 3 years before the
      diagnosis. The timing of previous endoscopies, indications for endoscopy,
      endoscopic findings and the number of biopsy specimens taken were recorded.
      Missed diagnoses were categorized as either definitely or possibly missed and the
      reasons for failure were documented. RESULTS: Of the 305 patients, 30 (9.8 %) had
      undergone a minimum of one endoscopy within the previous 3 years, 20 (67 %) of
      these within the previous 1 year. Sinister symptoms were present at the time of
      previous endoscopies in 75 % of patients with oesophageal cancer (n = 16) and in
      57.2 % of patients with gastric cancer (n = 14). In 56 % of the patients with
      oesophageal cancers the initial diagnosis was oesophagitis or benign stricture;
      in 71.4 % of the patients with gastric cancers the initial diagnosis was
      gastritis, ulcer or "suspicious lesion". Among those patients with a definitely
      missed diagnosis (7.2 %), endoscopist errors accounted for the majority of
      failures (73 %) and the remainder were due to pathologist errors (27 %).
      CONCLUSIONS: Missed cancers were a frequent finding in patients with oesophageal
      and gastric cancer who had undergone previous endoscopy, and errors by the
      endoscopists accounted for the majority of missed lesions. This study emphasizes
      the importance of identifying signs of early cancers and of having a low
      threshold for performing multiple biopsies of any suspicious-looking lesion.

PMID- 15452784
TI  - Causes and treatment of recurrent dysphagia after self-expanding metal stent
      placement for palliation of esophageal carcinoma.
AB  - BACKGROUND AND STUDY AIMS: Recurrent dysphagia frequently complicates the
      palliative treatment of esophageal cancer with self-expanding metal stents.
      Strategies for repeat interventions and subsequent outcomes have not been
      adequately reported to date. PATIENTS AND METHODS: A total of 216 patients
      underwent placement of a self-expanding metal stent (Ultraflex, n = 75; Flamingo
      Wallstent, n = 71; Z-stent, n = 70) for malignant dysphagia, and were followed up
      prospectively. The causes of stent-related recurrent dysphagia, the intervals
      after first stent placement, and the procedures used for repeat intervention and
      their outcomes were evaluated. RESULTS: Seventy-four episodes of stent-related
      recurrent dysphagia occurred in 63 patients (29 %), mainly due to tumor
      overgrowth (n = 30; median 129 days), stent migration (n = 26; median 92 days)
      and food bolus obstruction (n = 16; median 80 days). Stent migration occurred
      more frequently ( P = 0.05), whereas tumor overgrowth occurred less frequently (
      P = 0.05) with Ultraflex stents in comparison with Flamingo Wallstents and Z
      stents. Tumor overgrowth was treated in 25 patients mainly by a second stent (n =
      19) and was effective in 23 of the 25 patients (92 %). Five patients received no
      further treatment. Stent migration was treated by placing a second stent (n =
      14), repositioning the migrated stent (n = 7), other treatments (n = 3), or no
      further treatment (n = 2), and treatment was effective in 20 of 24 (83 %)
      patients. Food bolus obstruction was treated by endoscopic stent clearance in all
      patients. Repeat intervention for stent-related recurrent dysphagia improved the
      dysphagia score from a median of 3 to 1 ( P < 0.001). The median survival period
      after repeat treatment was 68 days. CONCLUSIONS: Recurrent dysphagia occurs in
      almost one-third of patients after stent placement. Repeat interventions for
      stent-related recurrent dysphagia are effective in over 90 % of patients. New
      innovations in stent design are needed to reduce the risk of stent-related
      recurrent dysphagia.

PMID- 15452785
TI  - Removal of a foreign body from the upper gastrointestinal tract with a flexible
      endoscope: a prospective study.
AB  - BACKGROUND AND STUDY AIMS: There have so far been no prospective studies on the
      value of flexible endoscopy for removing foreign bodies in the upper
      gastrointestinal tract. This study presents a clinical analysis of accidents with
      foreign bodies and prospectively evaluates the effectiveness of flexible
      endoscopy for removing them. PATIENTS AND METHODS: A total of 105 cases of
      foreign-body ingestion in the upper gastrointestinal tract were evaluated, 29
      (27.6 %) in children and 76 (72.4 %) in adults. Thirty patients (28.5 %) had
      esophageal strictures. RESULTS: Thirty-nine of the foreign bodies (37.1 %)
      consisted of food and 66 (62.9 %) were not food-related. The success rate of
      foreign-body extraction using only a conventional flexible endoscope and
      accessories for treatment was 98.0 %, and with only a polypectomy snare and rat
      toothed forceps it was 91.2 %. Complications at the moment of foreign-body
      removal occurred in nine patients (8.6 %); there was only one (1 %) esophageal
      perforation. The incidence of complications related to the duration of foreign
      body impaction was six (10.5 %) with foreign bodies impacted for up to 24 h, 13
      (52.0 %) for those impacted for 24-48 h, and three (60.0 %) for those impacted
      for 48-72 h ( P < 0.05). CONCLUSIONS: The flexible endoscope is an effective and
      safe device for removing foreign bodies from the upper gastrointestinal tract,
      with a high success rate using only the polypectomy snare and the rat-toothed
      forceps as accessories. If foreign-body impaction lasts for more than 24 h, there
      is a significant increase in the incidence of complications.

PMID- 15452786
TI  - Photodynamic therapy in normal pig stomach: protective effect of octreotide.
AB  - BACKGROUND AND STUDY AIMS: Many factors, such as oxygen and vasculature, are
      involved in the cytotoxic effect of photodynamic therapy (PDT). It is known that
      somatostatin and its analog octreotide decrease the splanchnic blood flow and
      have multiple inhibitory effects in different functions of the peptic system. The
      aim of this experimental study was to assess the effect of octreotide
      administration on PDT outcome in normal pig stomach. METHODS: 28 healthy pigs,
      randomly assigned to two groups, A and B, were studied. Pigs in both groups were
      sensitized with 0.3 mg/kg intravenous meta-tetra (hydroxyphenyl) chlorin (m
      THPC), and 48 hours later light of wavelength 650 nm was delivered from a 50-mW
      diode laser for 300 s (energy fluence 15 J/cm (2)) through a gastroscope to the
      gastric mucosa. Group A underwent PDT without octreotide and group B had PDT with
      administration of octreotide. At 72 h after light delivery, all the animals were
      sacrificed for macroscopic and histological evaluation of the irradiated site.
      RESULTS: The macroscopic images and the histology of the stomach PDT lesions
      (inflammation, ulceration, necrosis) showed significantly less severity in the
      group of animals with octreotide injection (group B). In this group, full
      thickness necrosis was observed in 28.5 %, compared with over 71.4 % in group A;
      this was statistically significant ( P < 0.05). CONCLUSION: Octreotide may have a
      modulating effect on m-TPHC PDT in normal gastric tissue in pigs, probably due to
      alterations of hemodynamics in the stomach and to suppression of the inflammatory
      process.

PMID- 15452787
TI  - Preventing postpolypectomy bleeding: obligatory and optional steps.

PMID- 15452788
TI  - Endoscopic ultrasound-guided fine-needle aspiration of celiac lymph nodes.

PMID- 15452789
TI  - Squamous reepithelialization after circumferential endoscopic mucosal resection
      of superficial carcinoma arising in Barrett's esophagus.
AB  - Recent reports on the results of endoscopic ablation of Barrett's mucosa have
      been promising, particularly when total mucosal ablation is coupled with
      aggressive acid-suppression treatment using high-dose proton-pump inhibitor
      therapy. There is also a considerable literature on reepithelialization after
      ablative treatments in Barrett's esophagus. This report describes a case of
      multifocal superficial adenocarcinoma arising in Barrett's mucosa that was
      successfully treated with total circumferential endoscopic mucosal resection,
      with a subsequent follow-up of more than 2 years. This is the first report
      describing the process of squamous reepithelialization after endoscopic mucosal
      resection in Barrett's esophagus.

PMID- 15452790
TI  - The role of video capsule endoscopy in the diagnosis of digestive diseases: a
      review of current possibilities.
AB  - Video capsule endoscopy represents a significant advance in the investigation of
      intestinal diseases. The performance of the procedure and indications are
      reviewed here in order to establish guidelines for its use, in accordance with
      current knowledge from the published literature. Capsule endoscopy is performed
      in patients who have fasted for 12 h, but who are allowed to drink 2 h after and
      to eat 4 h after ingesting the capsule. Software features highlighting suspected
      blood and allowing simultaneous viewing of two images reduce the time required to
      review the findings, as well as improving the diagnostic yield. Pacemakers and
      other electrical medical devices are no longer a contraindication to the
      procedure. Indications that have been validated include obscure digestive
      bleeding, intestinal lesions related to nonsteroidal anti-inflammatory drugs, and
      familial polyposis. Capsule endoscopy frequently detects intestinal lesions in
      patients with Crohn's disease and could become the first-choice examination in
      patients with suspected Crohn's disease after conventional endoscopic
      investigations. Other indications currently under evaluation include celiac
      disease, pediatric indications, and examination of other parts of the
      gastrointestinal tract.

PMID- 15452791
TI  - ESGE guidelines for quality control in servicing and repairing endoscopes.

PMID- 15452792
TI  - Endoscopic resection of early rectal carcinoid tumor.

PMID- 15452793
TI  - Limitations of cyanoacrylate injection in the treatment of gastric fundal
      varices.

PMID- 15452795
TI  - Heterotopic gastric mucosa of the rectum.

PMID- 15452796
TI  - Technique for endoscopic hemostasis of a bleeding peptic ulcer in a gastrostomy
      patient.

PMID- 15452797
TI  - Endoscopic removal of a ureterosigmoidal polyp.

PMID- 15452798
TI  - Video capsule endoscopy in a patient with a Billroth II gastrectomy and obscure
      bleeding.

PMID- 15452799
TI  - Common variable immunodeficiency: endoscopic and pathological findings.

PMID- 15452800
TI  - Endoscopic diagnosis of leukemia in a child with acute abdominal pain.

PMID- 15452801
TI  - Lifelong learning: a passion for the art of surgery.

PMID- 15452803
TI  - Effect of surgical reduction of the tongue on dentofacial structure following
      mandibular setback.
AB  - PURPOSE: The objective of this study was to examine the effect of partial
      glossectomy on skeletal stability and postoperative changes after mandibular
      setback. PATIENTS AND METHODS: Sagittal split ramus osteotomy with semirigid
      fixation was performed in 21 patients with tongue reduction surgery (tongue
      reduction group) and was performed in 19 patients without tongue reduction
      (control group). Lateral cephalograms were evaluated preoperatively, immediately
      postoperatively, and 1 year postoperatively, to analyze the maxillomandibular
      relation and soft tissue morphology. RESULTS: The results in both groups
      suggested that posterior and downward movement of the hyoid bone and narrowing of
      the upper pharyngeal airway at the tongue base were evident immediately
      postoperatively and rebounded to their original position 1 year after surgery.
      The tongue reduction had an effect to prevent narrowing of the posterior airway
      space and a tendency to reduce clockwise rotation of the mandible after the
      setback, but there was no significant difference between the 2 groups in the
      horizontal and vertical changes of incisal position at 1 year. CONCLUSION:
      Adaptation of the hyoid bone position and tongue mass to the altered environment
      after setback surgery may preclude the necessity for downsizing the tongue
      against the relapse in patients with normal tongue morphology.

PMID- 15452802
TI  - Neurosensory changes after liquid nitrogen cryotherapy.
AB  - PURPOSE: The study goal was to evaluate neurosensory changes after liquid
      nitrogen cryotherapy in the management of mandibular lesions in close proximity
      to the inferior alveolar nerve. PATIENTS AND METHODS: The design of the study was
      a retrospective review. Sixteen patients with posterior mandibular lesions (15
      odontogenic keratocysts and 1 fibromyxoma) in close proximity to the inferior
      alveolar nerve were treated with a standardized enucleation and cryotherapy
      technique. Postoperative evaluation included patients report of symptoms and
      formal neurosensory testing. RESULTS: All patients had altered sensation in the
      distribution of the inferior alveolar nerve immediately after cryotherapy. Two
      patients experienced anesthesia, and the remaining 14 patients showed
      paresthesia. The average time for return or improvement in sensation was 91 days
      (range, 6 to 235 days). The average time of follow-up was 2.6 years (range, 0.5
      to 7.3 years). At the time of last follow-up, no patients had anesthesia or
      dysesthesia. Four patients had full return of sensation and 12 patients had
      paresthesia. No patients reported significant difficulty from abnormal nerve
      function. All 16 patients experienced some return of sensation; 9 patients had
      full or near full return of sensation. CONCLUSIONS: Based on these results, the
      combination of enucleation and liquid nitrogen cryotherapy produces minimal
      alteration of inferior alveolar nerve function.

PMID- 15452805
TI  - Results of extracapsular dissection of pleomorphic adenoma of parotid gland.
AB  - PURPOSE: Current opinion that extracapsular dissection is in fact a euphemism for
      enucleation prompted us to retrospectively identify all patients in whom the
      extracapsular dissection technique was used and to critically assess the value of
      this technique. PATIENTS AND METHODS: The study includes all patients who
      underwent extracapsular dissection of parotid pleomorphic adenoma from 1979 to
      2002 in our department (Department of Surgical Oncology, Medical University of
      Lodz, Poland). Ninety-eight cases were evaluated. Mean tumor diameter was 3.6 cm
      (range, 1.5 to 10 cm; median, 3 cm). RESULTS: In 8 cases (8/98; 8.2%) local
      recurrence was observed. For the entire group, the probability of living 10 years
      without the recurrence of the disease was 0.58. The lowest probability of local
      recurrence was found in patients with tumors larger than 4 to 6 cm in diameter.
      In these cases, the extensiveness of resection was similar to superficial
      parotidectomy, which could explain the result. In 13 cases (13/98; 13.3%)
      capsular exposure was found and consequently microscopic disease was present at
      the excision margins. In 7 cases (7/98; 7.1%) capsular rupture took place during
      surgery. The persistent paresis of facial nerve was observed in 8 cases (8/98;
      8.2%). CONCLUSION: Extracapsular dissection of pleomorphic adenoma is a very
      demanding technique. Inevitable eventual clinical errors (eg, incomplete
      resection) lead to unacceptably high incidences of recurrences and complications.
      We do not advise this technique for the treatment of pleomorphic adenoma.

PMID- 15452804
TI  - Efficacy of steroid treatment for sensory impairment after orthognathic surgery.
AB  - PURPOSE: Steroid hormones are therapeutic for motor and/or sensory dysfunctions
      caused by nerve injury. However, the timing for giving such medicine is unclear.
      This study aimed to estimate the efficacy of steroid treatment and determine an
      appropriate start time after sensory impairment. PATIENTS AND METHODS: Twenty
      seven patients with sensory impairment who received orthognathic surgery were
      classified into groups called 1W (n = 6), 3W (n = 6), or 6W (n = 8) group on the
      basis of start time for steroid treatment, being 1 week, 3 weeks, or 6 weeks
      after surgery, respectively, and a no steroid treatment (NST) group (a control
      group) (n = 6) that did not receive treatment for 10 to 12 weeks after surgery.
      Sensory impairment was diagnosed if postoperative first week mechanical-touch
      threshold was over 4.0 as measured by Semmes aesthesiometer. Prednisolone
      treatment was administered orally to patients at 30 mg for 7 days, 15 mg for 4
      days, and 5 mg for 3 days. Mechanical-touch threshold and thermal perceptions
      were compared before and after treatment. RESULTS: At 1 week postoperatively,
      there were no significant differences in mechanical-touch threshold among the 4
      groups (analysis of variance, P >.05). Changes in mechanical-touch threshold in
      the 1W group showed no significant improvement (analysis of variance, P >.05),
      but in the 3W and 6W groups, there were significant differences compared with the
      NST group (Dunns methods, P <.05). CONCLUSIONS: Steroid treatment for sensory
      impairment after orthognathic surgery has the potential to accelerate recovery
      and it appears desirable to start treatment later than 1 week postoperatively.

PMID- 15452806
TI  - Tumors of the submandibular gland: clinicopathologic analysis of 23 patients.
AB  - PURPOSE: Tumors of the submandibular gland are rare, comprising less than 2% of
      head and neck neoplasia. Both benign and malignant lesions show a mild
      symptomatology, resulting in late presentation and in advanced stage of disease.
      The purpose of this article was to report our experience in treating
      submandibular gland neoplasia during the last 10 years. PATIENTS AND METHODS: The
      medical records of all patients with histologically confirmed epithelial tumors
      of the submandibular gland were retrospectively reviewed. This review found 23
      patients with 9 benign and 14 malignant tumors. The collection of data included
      demographic data, diagnostic procedures, operative and pathology reports,
      complications, additional treatment, and follow-up. RESULTS: There were 10 men
      and 13 women with a mean age of 60 years. Pleomorphic adenoma was the most
      frequently encountered benign tumor; adenocarcinoma and adenoid cystic carcinoma
      had an equal presentation in the malignant group of patients. Eleven of the 14
      patients with malignant tumors presented in advanced stages of disease (stage III
      and IV). Surgery was the sole treatment for the benign tumors. There were no
      recurrences. In the majority of cases, patients with malignant tumors were
      treated with surgery and postoperative radiotherapy. Eight patients died during
      the follow-up period, giving a mortality rate of 61.5%. CONCLUSION: Benign
      submandibular gland tumors manifest a mild course of disease, and local excision
      along with the gland is a safe and effective method of treatment. Malignant
      tumors have a poor symptomatology that results in late diagnosis. Radical surgery
      and postoperative radiotherapy is the treatment of choice. Prognosis depends on
      the histopathology and biologic behavior of the specific type of malignant tumor.

PMID- 15452807
TI  - Craniomaxillofacial fractures during recreational baseball and softball.
AB  - PURPOSE: Baseball and softball are leading causes of sports-related facial trauma
      in the United States. We review our institutional experience (Strong Memorial
      Hospital, Rochester, NY) with these injuries and discuss measures to reduce their
      incidence. PATIENTS AND METHODS: We review our institutions experience with
      facial fractures sustained during the course of a softball or baseball game over
      a 12-year period. A total of 38 patients were identified and medical records
      analyzed for patient demographics, type of impact, and fracture location.
      RESULTS: The male-to-female ratio was 3.2:1; mean age was 24.2 years, with 17
      (45%) of the injuries occurring in the pediatric population. The majority of the
      injuries were caused by direct impact with the ball (68%), while player-player
      collisions (18%) and impact from a swung bat (13%) were responsible for the
      remaining injuries. There were a total of 39 fractures; 18 fractures (46%)
      involved the midface (level 2), skull (level 1) fractures accounted for 12 (31%),
      while 9 (23%) were mandibular (level 3) fractures. CONCLUSION: With 68% of the
      injuries resulting from a ball impact, we endorse the recommendations of the
      Consumer Product Safety Commission for the use of low-impact National Operating
      Committee on Standards for Athletic Equipment-approved baseballs and softballs
      for youth and recreational leagues.

PMID- 15452808
TI  - Management of mandibular third molar extraction sites to prevent periodontal
      defects.
AB  - PURPOSE: Persistent periodontal defects on the distal aspect of the mandibular
      second molar (M2) is a reported complication of mandibular third molar (M3)
      extraction. The purpose of this study was to measure the efficacy of
      demineralized bone powder (DBP) or guided-tissue regeneration therapy (GTR
      therapy) in preventing periodontal defects on the distal aspect of the M2
      following M3 extraction. MATERIALS AND METHODS: We implemented a single-blind,
      randomized, controlled clinical trial composed of a sample of subjects > or = 26
      years of age who required extraction of bilateral M3s. The primary predictor
      variable was treatment group. Each subject was randomly assigned to receive
      either DBP or GTR therapy. Within subjects, 1 M3 site was randomly selected to be
      the experimental site and the opposite M3 served as a control and was permitted
      to heal without intervention. The primary outcome variable was the change in
      attachment levels (AL) and probing depths (PD) on the disto-buccal aspect of M2
      between T 0 (immediate preoperatively) and T 4 (26 weeks postoperatively).
      Appropriate sample size estimates, descriptive, bivariate, and multivariate
      statistics were computed. RESULTS: Twelve subjects in the DBP group and 12
      subjects in the GTR-therapy group completed the study. For both treatment and
      control sites, between T 0 and T 4, there were statistically significant
      improvements in AL (> or = 2.2 mm; P <.001) and PD (> or = 2.6 mm; P <.001).
      Within-subjects comparisons showed no significant differences in AL or PD between
      treatment and control M3 sites ( P > or =.3) at T 0 or T 4. CONCLUSION: The
      results of this study suggest that attachment levels and probing depths improve
      after M3 removal. In this sample, DBP or GTR therapy did not offer predictable
      benefit over no treatment.

PMID- 15452809
TI  - Contralateral neck recurrence of squamous cell carcinoma of oral cavity and
      oropharynx.
AB  - PURPOSE: Contralateral neck failure after therapy for squamous cell carcinoma of
      the oral cavity and oropharynx has rarely been studied in detail. We aimed to
      examine the pattern and outcome of contralateral neck relapse and possible
      predictive clinicopathologic factors. PATIENTS AND METHODS: Seventy-three
      patients undergoing surgery for cancer of oral cavity/oropharynx with curative
      intent were recruited from the hospital head and neck cancer registry. The age,
      gender, tumor site, primary tumor laterality, TNM status, clinical N status,
      pathologic T status, ipsilateral pathologic N status, tumor stage, status of
      residual disease, histopathologic differentiation, postoperative radiotherapy,
      local relapse, distant relapse, extracapsular spread of lymph node metastasis and
      neck dissection were evaluated for association with contralateral neck relapse.
      RESULTS: Seven patients developed ipsilateral, 5 patients developed
      contralateral, and 3 patients developed bilateral neck recurrence after therapy.
      Only 1 patient with contralateral or bilateral neck relapse survived after
      salvage therapy. Ipsilateral positive nodal status was the only significant
      clinicopathologic parameter associated with contralateral neck relapse, which
      occurred rather commonly in well-lateralized tumors. CONCLUSION: Contralateral
      and ipsilateral neck relapses are similar in occurrence. Pathologic positive
      nodal status is associated with a higher incidence of contralateral neck relapse.
      Aggressive and comprehensive adjuvant radiotherapy to the neck plus close
      surveillance in the first 2 years postoperatively might curtail the frequency and
      mortality due to contralateral neck failure.

PMID- 15452810
TI  - Evaluation of maxillary sinus after treatment of midfacial fractures.
AB  - PURPOSE: Maxillary sinuses are the most frequently injured anatomic region of the
      facial skeleton in midfacial fractures. The purpose of this study was to evaluate
      the patients with maxillary sinus wall fractures using clinical examinations,
      maxillofacial computed tomography (CT), and cranial bone single-photon emission
      tomography (SPECT) and to interpret the results of these examinations to evaluate
      the indications of surgical intervention or drainage for maxillary sinus after
      maxillary sinus wall fractures. MATERIALS AND METHODS: The results of
      examinations of 15 patients with maxillary sinus fractures who were treated for
      midfacial fractures were evaluated. Follow-up examinations were performed in the
      range of 3 to 47 months after surgery (average, 19.8 months). The patients ranged
      in age from 10 to 45 years, with an average age of 31.6 years. There were 11 male
      and 4 female patients. Seven patients had Le Fort II fractures, 6 patients had
      tripod zygomatic fractures, 1 patient had infraorbital fracture, and 1 patient
      had zygomatic arch fracture. Operative procedure was performed in all cases. To
      evaluate maxillary sinus after surgery, maxillofacial computed tomography (CT),
      cranial bone SPECT, and maxillary sinusitis evaluation form were used in all
      patients. RESULTS: Maxillofacial CT scans were related to sinusitis in 9 patients
      who had positive complaints for sinusitis. The cranial bone SPECT showed positive
      uptake at the fractured sites in 8 patients, minimal uptake in 2 patients, and
      normal uptake in 5 patients. CONCLUSIONS: Clinical examination, maxillofacial CT,
      and cranial bone SPECT are the most reliable methods available today for the
      diagnosis and follow-up of complications of maxillary sinus fractures.

PMID- 15452811
TI  - Clinical application of magnetic resonance sialographic 3-dimensional
      reconstruction imaging and magnetic resonance virtual endoscopy for salivary
      gland duct analysis.
AB  - PURPOSE: In a previous study, we showed that the new and fast sequence 3
      dimensional (3D)-fast asymmetric spin-echo sequencing could be applied in
      magnetic resonance (MR) sialographic 3D reconstruction imaging of the parotid
      gland ducts and in producing virtual endoscopic views of the parotid gland with
      MR data. MATERIALS AND METHODS: In the present study, we examined the clinical
      application of these MR sialographic 3D reconstruction imaging and virtual
      endoscopy of the salivary gland ducts using MR data sets with 3D-fast asymmetric
      spin-echo sequencing. RESULTS: The MR sialographic 3D reconstruction images
      showed a complete view in the branch paths from all angles, and the MR virtual
      endoscopic views showed conditions in the endoluminal tracts of the large
      branches in 20 patients with salivary gland duct abnormalities, including Sjogren
      syndrome, cyst, tumor, sialadenitis, and salivary calculi. CONCLUSION: The
      clinical use of MR sialographic 3D reconstruction imaging and MR virtual
      endoscopy for salivary gland ducts may enhance understanding of the 3D
      relationship between the ducts and the surrounding tissue, as well as the
      endoluminal circumstance within ducts. Possible future applications abound, and
      further investigation in this field is expected.

PMID- 15452812
TI  - Advantages of intraoral verticosagittal ramus osteotomy in skeletofacial
      deformity patients with temporomandibular joint disorders.
AB  - PURPOSE: This preliminary study was performed to clarify the usefulness of
      intraoral verticosagittal ramus osteotomy (IVSRO) in patients with
      temporomandibular joint (TMJ) disorders. PATIENTS AND METHODS: We examined 34
      sides in 19 consecutive patients with dentofacial deformities with TMJ
      dysfunction undergoing IVSRO. Preoperatively, 15 patients had TMJ sounds
      bilaterally and 4 had sounds unilaterally. Five sides in 3 patients had pain in
      the TMJ, and 4 sides in 3 patients had masticatory muscle pain. The TMJ symptoms,
      including TMJ sounds, pain in the TMJ, and masticatory muscle pain in each
      patient, were assessed clinically before and approximately 12 months after IVSRO.
      Magnetic resonance imaging was also performed to determine joint status,
      including determination of the positions of the condyle and disc. RESULTS: The
      symptoms of the TMJ after 12 months of orthodontic treatment showed marked
      improvements, with the disappearance of the TMJ sounds in 94% of the sides
      examined. Pain in the TMJ improved in 4 of 5 sides, and pain of the masticatory
      muscle improved in 3 of 4 sides. With regard to the relative positions of the
      condyle and disc on magnetic resonance imaging, 6 of 8 joints and 5 of 7 joints
      showed improvement in anterior disc displacement with and without reduction,
      respectively. The direction and mean amount of movement in the distal segment
      were 8 mm in setback, 4 mm in advance, and 5 mm counterclockwise. CONCLUSION:
      IVSRO is potentially as useful for the treatment of TMJ disorders in orthognathic
      surgery patients as is intraoral vertical ramus osteotomy, and IVSRO can be used
      selectively in cases in which intraoral vertical ramus osteotomy is
      contraindicated.

PMID- 15452813
TI  - Micromorphology of sialoliths in submandibular salivary gland: a scanning
      electron microscope and X-ray diffraction analysis.
AB  - PURPOSE: Sialoliths are common in the submandibular gland and its duct system.
      The exact cause of formation of a sialolith is still a matter of debate. The aim
      of this study was to analyze 6 sialoliths ultrastructurally to determine their
      development mechanism in the submandibular salivary glands. MATERIALS AND
      METHODS: Six sialoliths retrieved from the hilus and duct of the submandibular
      salivary glands of 6 patients with sialadenitis were analyzed ultrastructurally
      by scanning electron microscope and x-ray diffractometer. RESULTS: Scanning
      electron microscope revealed mainly irregular, partly rudely hexagonal, needle
      like and plate-shaped crystals. The cross-section from the surface to the inner
      part of the sialoliths showed no organic material. X-ray diffraction showed that
      the sialoliths were composed of hydroxyapatite crystals. Energy dispersive x-ray
      microanalysis showed that all of the samples contained high levels of Ca and P,
      and small amounts of Mg, Na, Cl, Si, Fe, and K. CONCLUSION: The main structures
      of the submandibular sialoliths were found to be hydroxyapatite crystals. No
      organic cores were observed in the central parts of the sialoliths. In accordance
      with these preliminary results, sialoliths in the submandibular salivary glands
      may arise secondary to sialadenitis, but not via a luminal organic nidus.

PMID- 15452814
TI  - Biomechanical evaluation of the pins of a mandibular external distractor.
AB  - PURPOSE: Our goal was to establish whether the pins of an external distractor
      were capable of overcoming tissue resistance to distraction. MATERIALS AND
      METHODS: The study was carried out in 2 parts. The first part of the study
      determined the bending rigidity of the distractors pins. To accomplish this, the
      distractor was installed on the mandible of a stereolithographic model using 4
      regular 2.0-mm steel pins. An osteotomy was not performed. The distractor was
      activated using a torque gauge, and the bending rigidity of the pins was
      recorded. The second part of the study determined the tissue resistance to
      mandibular distraction using fresh cadavers. Six cadavers were divided into 2
      groups to determine tissue resistance to angular and linear distraction,
      respectively. The devices used to measure tissue resistance were a modified
      external multiplanar distractor and a torque gauge. RESULTS: In the
      anteroposterior direction, the tissue resistance to linear distraction clearly
      exceeded the bending rigidity of the pins for the first 7.5 mm of activation.
      After this, the opposite was true. In the vertical direction, the tissue
      resistance clearly exceeded the bending rigidity of the pins for the first 8.0 mm
      of activation. After this, the opposite was true. For the first 15.0 degrees of
      angular distraction in the sagittal plane, the tissue resistance was almost
      identical to the bending rigidity of the pins. After this, the tissue resistance
      significantly exceeded the bending rigidity of the pins. For the first 7.0
      degrees of angular distraction in the transverse plane, the tissue resistance was
      marginally greater than the bending rigidity of the pins. After this, the bending
      rigidity of the pins increased significantly. CONCLUSION: The 2.0-mm steel pins
      used in most external multiplanar distractors are not capable of overcoming the
      tissue resistance to linear or angular distraction.

PMID- 15452815
TI  - Lesion in the maxilla with a multicystic appearance.

PMID- 15452816
TI  - Endoscopic open reduction and internal rigid fixation of subcondylar fractures.

PMID- 15452817
TI  - Traditional versus endoscope-assisted open reduction with rigid internal fixation
      (ORIF) of adult mandibular condyle fractures: a review of the literature
      regarding current thoughts on management.

PMID- 15452818
TI  - Biomaterials for reconstruction of the internal orbit.

PMID- 15452819
TI  - Evaluation of ocular changes secondary to blowout fractures.
AB  - There has been extensive debate over the standard of care of orbital fractures.
      Entrapment, diplopia, and hypoglobus, with or without enophthalmos, are the most
      common clinical indications for surgical intervention. Evaluation of these
      injuries is often limited in the early postinjury period because of edema. In
      assessing the severity of the injury, the clinician often uses parameters such as
      changes in visual acuity, patient-reported diplopia, gross changes in globe
      position, and an evaluation of the extraocular muscles. Many of these parameters
      are only grossly assessed and therefore are not specifically documented and
      tracked. The decision to proceed with surgical intervention may be based only on
      these gross clinical findings. The purpose of this article is to present a
      reliable and repeatable method for evaluating the degree of diplopia and the
      globe position of the orbital trauma patient by describing the use of the double
      Maddox rod test (Wilson Ophthalmic, Mustang, OK) and Hertel exophthalmometer
      (Wilson Ophthalmic). These methods can provide sequential documentation of the
      progression of the injury and help better define the need for surgical
      intervention and to follow the postoperative course.

PMID- 15452820
TI  - Simon P. Hullihen and the origin of orthognathic surgery.

PMID- 15452821
TI  - Venous malformation of the orbit.

PMID- 15452822
TI  - Secondary correction of malocclusion after treatment of maxillofacial trauma.

PMID- 15452823
TI  - Parotid area lymphangioma in an adult: case report.

PMID- 15452824
TI  - Severe corneal edema after temporomandibular joint reconstruction: report of a
      case.

PMID- 15452826
TI  - Low density of membrane particles in auditory hair cells of lizards and birds
      suggests an absence of somatic motility.
AB  - Hair cells are the mechanoreceptive cells of the vertebrate lateral line and
      inner ear. In addition to their sensory function, hair cells display motility and
      thus themselves generate mechanical energy, which is thought to enhance
      sensitivity. Two principal cellular mechanism are known that can mediate hair
      cell motility in vitro. One of these is based on voltage-dependent changes of an
      intramembrane protein and has so far been demonstrated only in outer hair cells
      of the mammalian cochlea. Correlated with this, the cell membranes of outer hair
      cells carry an extreme density of embedded particles, as revealed by freeze
      fracturing. The present study explored the possibility of membrane-based motility
      in hair cells of nonmammals, by determining their density of intramembrane
      particles. Replicas of freeze-fractured membrane were prepared from auditory hair
      cells of a lizard, the Tokay gecko, and a bird, the barn owl. These species were
      chosen because of independent evidence for active cochlear mechanics, in the form
      of spontaneous otoacoustic emissions. For quantitative comparison, mammalian
      inner and outer hair cells, as well as vestibular hair, cells were reevaluated.
      Lizard and bird hair cells displayed median densities of 2,360 and 1,880
      intramembrane particles/microm2, respectively. This was not significantly
      different from the densities in vestibular and mammalian inner hair cells;
      however, it was about half the density in of mammalian outer hair cells. This
      suggests that nonmammalian hair cells do not possess high densities of motor
      protein in their membranes and are thus unlikely to be capable of somatic
      motility.

PMID- 15452827
TI  - Distribution of zincergic neurons in the mouse forebrain.
AB  - Synaptically released zinc is thought to play an important role in neuronal
      signaling by modulating excitatory and inhibitory receptors and intracellular
      signaling proteins. Consequently, neurons that release zinc have been implicated
      in synaptic plasticity underlying learning and memory as well as
      neuropathological processes such as epilepsy, stroke, and Alzheimer's disease. To
      characterize the distribution of these neurons, investigators have relied on a
      technique that involves the retrograde transport of zinc-selenium crystals from
      axonal boutons to the cell bodies of origin. However, one major problem with this
      method is that labeling of cell bodies is obscured by high levels of staining in
      synaptic boutons, particularly within forebrain structures where this staining is
      most intense. Here, we used a modification of the retrograde labeling method that
      eliminates terminal staining for zinc, thereby enabling a clear and comprehensive
      description of these neurons. Zincergic neurons were found in all cerebral
      cortical regions and were arranged in a distinct laminar pattern, restricted to
      layers 2/3, 5, and 6 with no labeling in layer 4. In the hippocampus, labeling
      was present in CA1, CA3, and the dentate gyrus but not in CA2. Labeled cell
      bodies were also observed in most amygdaloid nuclei, anterior olfactory nuclei,
      claustrum, tenia tecta, endopiriform region, lateral ventricle, lateral septum,
      zona incerta, superior colliculus, and periaqueductal gray. Moreover, retrograde
      labeling was also noted in the dorsomedial and lateral hypothalamus, regions that
      previously were thought to be devoid of neurons with a zincergic phenotype.
      Collectively these data show that zincergic neurons comprise a large population
      of neurons in the murine forebrain and will provide an anatomical framework for
      understanding the functional importance of these neurons in the mammalian brain.

PMID- 15452828
TI  - Localization and connectivity of the lateral amygdala in anuran amphibians.
AB  - On the basis of chemoarchitecture and gene expression patterns in the amphibian
      amygdaloid complex, new subdivisions have been proposed and compared with their
      counterparts in amniotes. Thus, a portion of the ventral pallium of anurans has
      been tentatively named "lateral amygdala" (LA) and compared with the basolateral
      complex of mammals. To strengthen the putative homology, we have analyzed the
      pattern of afferent and efferent connections of the LA in the anurans Rana perezi
      and Xenopus laevis. Tract-tracing techniques with dextran amines were used under
      in vivo and in vitro conditions. The results showed important connections with
      the main olfactory bulb, via the lateral olfactory tract. In addition, abundant
      intratelencephalic connections, via the rostral branch of the stria terminalis,
      were revealed, involving mainly the basal ganglia, septal nuclei, bed nucleus of
      the stria terminalis, and especially other amygdaloid nuclei. Nontelencephalic
      connections were found from the dorsal thalamus and parabrachial area and, in
      particular, from the hypothalamus through the caudal branch of the stria
      terminalis. All these results strongly suggest that the LA in anurans is a
      multimodal area in the ventral pallium that shares many hodological features with
      the amygdaloid ventropallial derivatives of the basolateral complex of amniotes.

PMID- 15452829
TI  - Twitch and nontwitch motoneuron subgroups in the oculomotor nucleus of monkeys
      receive different afferent projections.
AB  - Motoneurons in the primate oculomotor nucleus can be divided into two categories,
      those supplying twitch muscle fibers and those supplying nontwitch muscle fibers.
      Recent studies have shown that twitch motoneurons lie within the classical
      oculomotor nucleus (nIII), and nontwitch motoneurons lie around the borders.
      Nontwitch motoneurons of medial and inferior rectus are in the C group
      dorsomedial to nIII, whereas those of inferior oblique and superior rectus lie
      near the midline are in the S group. In this anatomical study, afferents to the
      twitch and nontwitch subgroups of nIII have been anterogradely labeled by
      injections of tritiated leucine into three areas and compared. 1) Abducens
      nucleus injections gave rise to silver grain deposits over all medial rectus
      subgroups, both twitch and nontwitch. 2) Laterally placed vestibular complex
      injections that included the central superior vestibular nucleus labeled
      projections only in twitch motoneuron subgroups. However, injections into the
      parvocellular medial vestibular nucleus (mvp), or Y group, resulted in labeled
      terminals over both twitch and nontwitch motoneurons. 3) Pretectal injections
      that included the nucleus of the optic tract (NOT), and the olivary pretectal
      nucleus (OLN), labeled terminals only over nontwitch motoneurons, in the
      contralateral C group and in the S group. Our study demonstrates that twitch and
      nontwitch motoneuron subgroups do not receive identical afferent inputs. They can
      be controlled either in parallel, or independently, suggesting that they have
      basically different functions. We propose that twitch motoneurons primarily drive
      eye movements and nontwitch motoneurons the tonic muscle activity, as in gaze
      holding and vergence, possibly involving a proprioceptive feedback system.

PMID- 15452830
TI  - Differential localization and expression of the Cdk9 42k and 55k isoforms.
AB  - Cdk9, a member of the cyclin-dependent kinase family, is the catalytic subunit of
      P-TEFb, a protein kinase complex that stimulates transcriptional elongation.
      Cdk9, complexed with its regulatory partner cyclin T1, serves as the cellular
      mediator of the transactivation function of the HIV Tat protein. There are two
      known isoforms of Cdk9: a 42 kDa protein (42k, originally identified as PITALRE)
      and a more recently identified 55 kDa form (55k). To investigate possible
      functional differences between the two isoforms, we examined their kinase
      activities, their subcellular distributions, and their expression levels in
      primary cells relevant to HIV infection. Both isoforms were found to hyper
      phosphorylate the carboxyl-terminal domain of the largest subunit of RNA
      polymerase II and displayed identical phosphorylation patterns with 144 peptide
      substrates. Epitope-tagged transiently-expressed Cdk9 42k localized diffusely in
      the nucleoplasm, while Cdk9 55k accumulated in the nucleolus. In primary
      undifferentiated monocytes, Cdk9 55k expression was not detected although 42k was
      present at high levels; however, 55k expression was induced upon macrophage
      differentiation. In primary lymphocytes, the levels of 55k decreased or remained
      steady following activation, while the levels of 42k increased. The promoter for
      42k was significantly stronger than that of 55k in HeLa cells, and only the 42k
      promoter was responsive to activation signals in primary lymphocytes. These
      results indicate that expression of the 42k and 55k isoforms is differentially
      regulated and suggest that functional differences between the 42k and 55k
      isoforms of Cdk9 are likely to depend on access to substrates based on their
      differential subcellular localization and expression patterns.

PMID- 15452831
TI  - Activation of mitochondrial lactate uptake by flavone induces apoptosis in human
      colon cancer cells.
AB  - Lactate production from glucose even in the presence of oxygen is a
      characteristic of cancer cell metabolism and an important feature for tumor
      progression. Here, we describe that an increased uptake of lactate into
      mitochondria of HT-29 human colon cancer cells by treatment of cells with the
      flavonoid flavone is associated with an increased production of mitochondrial
      superoxide anions and apoptotic cell death. In search of the mitochondrial
      transporter that could promote enhanced lactate uptake and energetic flow through
      the electron transport chain, we used fluorescein as a model substrate. Flavone
      increased fluorescein uptake at pH 7.4 into mitochondria of HT-29 cells almost
      tenfold while lactate inhibited uptake significantly. Uptake of fluorescein in
      the absence or presence of flavone was strongly increased by lowering pH from 7.4
      to 6.0 and almost abolished by the protonophore carbonyl cyanide m
      chlorophenylhydrazone (CCCP). The lactate-sensitive part of fluorescein transport
      was completely blocked by p-chloromercuribenzenesulfonic acid (pCMBS), a specific
      inhibitor of the monocarboxylate transporter-1 (MCT-1) that by Western blotting
      and immunofluorescence was identified in mitochondria of HT-29 cells. Finally,
      lactate increased and pCMBS inhibited the flavone-induced generation of
      mitochondrial O2-* radicals and in turn blunted the apoptotic response. In
      conclusion, our studies provide evidence that flavone reverts the metabolic
      phenotype of transformed colonocytes towards a phenotype characteristic for
      normal cells. Transformed colonocytes, however, seem especially vulnerable to O2
      *, produced in mitochondria as a consequence of these metabolic alterations, and
      respond with the induction of apoptosis.

PMID- 15452832
TI  - Invasive aspergillosis in patients with solid tumors.
AB  - Invasive aspergillosis (IA) has been reported only rarely among patients with
      solid tumors. In the current study, the authors retrospectively identified 13
      episodes of definite or probable IA (using European Organization for Research and
      Treatment of Cancer criteria) occurring in patients with solid tumors who were
      treated between 1994-2003. Nine patients had pulmonary IA and three patients were
      found to have IA of the brain. Seven patients (54%) had primary or metastatic
      brain tumors and 6 patients (46%) received systemic steroids within 30 days prior
      to the diagnosis of IA. The majority of patients (69%) had a lymphocyte count <
      500/microL but only 1 patient was neutropenic within the 30 days before the
      diagnosis of IA was made. Nodular infiltrates and cavities were the most common
      radiologic findings. Seven patients (54%) responded to antifungal treatment.

PMID- 15452833
TI  - Uterine serous and grade 3 endometrioid carcinomas: is there a survival
      difference?
AB  - BACKGROUND: Serous components within endometrial carcinoma are reportedly poor
      prognosticators. However, to the authors' knowledge the percentage of tumors
      which must be comprised of a serous component in order to affect outcome is
      unknown. The authors compared overall survival (OS) in women with endometrial
      carcinomas comprised of various percentages of uterine serous carcinoma (USC)
      with that of women with International Federation of Gynecology and Obstetrics
      (FIGO) Grade 3 endometrioid carcinoma (G3EC) to determine whether outcomes varied
      between these two poorly differentiated histologies. METHODS: Data concerning
      women with either G3EC or USC who were diagnosed between January 1990 and
      November 2000 were collected retrospectively. Cases were reviewed to confirm
      diagnosis and estimate the fraction of tumor comprised of USC. Variables assessed
      included patient age and race, tumor stage, and lymphovascular space invasion.
      Associations between variables were tested using the Fisher exact test. The
      Kaplan-Meier method was used to evaluate OS with comparisons performed using the
      log-rank test. RESULTS: Fifty-two women with G3EC and 87 women with USC were
      identified. The OS of women with tumors comprised of > 50% USC was found to be
      significantly worse compared with women with G3EC (hazard ratio [HR] of 2.4; 95%
      confidence interval [95% CI], 1.2-5.2). Women with USC were more likely to
      present with extrauterine disease (odds ratio of 2.2; 95% CI, 1.1-4.5). The 5
      year survival rate for women with G3EC was 75% compared with 41% for women with
      tumors that were > 50% USC (P = 0.01). There was a significant trend toward a
      worse OS in women with even 10% USC compared with women with G3EC. CONCLUSIONS:
      USC involving > 50% of an endometrial carcinoma was found to be predictive of
      worse OS compared with the OS of women with G3EC. In patients with early-stage
      disease, a trend toward a worse prognosis was found to exist when USC comprised
      even 10% of a tumor. Investigation into the treatment of endometrial carcinoma
      should include and document tumors with any percentage comprised of USC.

PMID- 15452834
TI  - Prognostic factors and long-term survivorship in patients with recurrent or
      metastatic carcinoma of the head and neck.
AB  - BACKGROUND: The current study was conducted to identify prognostic factors and
      report the characteristics of long-term survivors in patients with recurrent or
      metastatic carcinoma of the head and neck who were treated with cisplatin-based
      combination chemotherapy in two randomized, Phase III trials conducted by the
      Eastern Oncology Cooperative Group (ECOG) (E1393 and E1395). METHODS: The authors
      analyzed prognostic factors for response and survival by combining data from the
      E1393 trial, which compared cisplatin plus paclitaxel at two dose levels, with
      data from the E1395 trial, which compared cisplatin plus paclitaxel with
      cisplatin plus 5-fluorouracil (5-FU), using logistic regression and Cox
      regression models. RESULTS: A total of 399 eligible patients were included. The
      median follow-up was 4.7 years. The 1-year overall survival (OS) rate for all
      patients was 32%, the median OS was 7.8 months, and the objective response rate
      was 32%. On multivariate analysis, the following were found to be independent
      unfavorable predictors of objective response: weight loss of > 5%, an ECOG
      performance status of 1 (vs. 0), residual disease at the primary tumor site, a
      primary tumor site other than the oropharynx, prior radiation therapy (RT) (P =
      0.056), and well/moderate tumor cell differentiation (P = 0.067). Independent
      unfavorable prognostic factors for OS were weight loss, an ECOG performance
      status of 1 (vs. 0), well/moderate tumor cell differentiation, a primary tumor in
      the oral cavity or hypopharynx, and prior RT. The following were found to be
      independent unfavorable prognostic factors for time to disease progression:
      well/moderate tumor cell differentiation, a oral cavity or hypopharyngeal primary
      tumor, and prior RT. Patients with < or = 2 adverse prognostic factors were
      reported to have a median OS of 1 year, whereas patients with 3-5 adverse
      prognostic factors were found to have a median OS of 0.5 years (P < 0.0001).
      Forty-nine patients (12%) survived for > or = 2 years and 6 patients were alive
      at 5 years. Two-year survivors were more likely to have achieved an objective
      response to chemotherapy, have poor tumor cell differentiation, be white, have an
      ECOG performance status of 0, and have received no prior RT. CONCLUSIONS:
      Clinical parameters and tumor cell differentiation appear to be strong
      pretreatment predictors of outcome in patients with carcinoma of the head and
      neck and should be considered in the design of future randomized trials. A small
      percentage of patients with recurrent head and neck carcinoma can achieve long
      term survival.

PMID- 15452835
TI  - Cross-sectional and longitudinal comparisons of health-related quality of life
      between patients with prostate carcinoma and matched controls.
AB  - BACKGROUND: Prostate carcinoma and treatments affect health-related quality of
      life (HRQOL). The authors prospectively compared prostate and general HRQOL
      between prostate carcinoma cases and an age-matched and ethnicity-matched control
      group. METHODS: The case cohort consisted of 293 men with localized prostate
      carcinoma who were selected randomly from the population-based New Mexico Tumor
      Registry, and the control cohort consisted of 618 men who were selected randomly
      from administrative databases and matched for age and ethnicity. Subjects
      completed a baseline survey of demographics, socioeconomic status, comorbidity,
      and prostate and general HRQOL. Also, 210 cases (71.7%) and 421 controls (67.8%)
      completed a follow-up survey 5 years later. Multinomial logistic regression
      models compared baseline characteristics as well as 5-year general HRQOL outcomes
      measured by selected domains of the Medical Outcomes Study SF-36. The authors
      used a mixed-model repeated-measures analysis of variance and multinomial
      regression analyses to compare longitudinal changes in urinary, bowel, and sexual
      function between groups. RESULTS: At baseline, patients with prostate carcinoma
      had better urinary control and sexual function than controls. Over 5 years,
      sexual function declined significantly among controls, although urinary function
      remained stable. However, patients with cancer subsequently reported significant
      declines in both domains and were left with much worse function and more bother
      than controls. Bowel function and general HRQOL were similar for both groups at
      follow-up. CONCLUSIONS: Prostate carcinoma treatment led to significant 5-year
      declines in urinary and sexual function that far exceeded age-related changes in
      controls. Patients with cancer had significantly worse function and more bother
      than controls for these disease-specific domains of HRQOL. Bowel function and
      general HRQOL were not affected by cancer status.

PMID- 15452836
TI  - Systematic review of adjuvant care for women with Stage I ovarian carcinoma.
AB  - BACKGROUND: Several adjuvant care interventions to treat women with Stage I
      ovarian carcinoma have been studied. The aim of the current systematic review was
      to determine the optimal strategy for adjuvant care for women with Stage I
      ovarian carcinoma. METHODS: A systematic search was conducted to find randomized
      controlled trials published between 1965 and April 2004 that examined adjuvant
      therapy (e.g., chemotherapy and radiotherapy) for women with Stage I ovarian
      carcinoma. RESULTS: Thirteen randomized controlled trials were identified that
      compared adjuvant therapies for women with Stage I ovarian carcinoma. Eight of
      these trials reported results only for patients with Stage I disease. The
      majority of patients in the five randomized trials that compared adjuvant
      chemotherapy with no chemotherapy did not receive lymphadenectomy as part of
      their surgical staging. The pooled results for Stage I patients indicated a
      survival benefit (relative risk [RR], 0.74; 95% confidence interval [CI], 0.58
      0.94; P = 0.01), and a benefit in terms of a reduced risk of developing disease
      recurrence (RR, 0.70; 95% CI, 0.58-0.86; P = 0.0004) favoring adjuvant
      chemotherapy. Platinum-based adjuvant chemotherapy was reported to improve
      overall 5-year survival (absolute survival difference 8%; 95% CI, 2-12%; hazard
      ratio, 0.67; 95% CI, 0.50-0.90; P = 0.008). CONCLUSIONS: Adjuvant platinum-based
      chemotherapy for women with Stage I ovarian carcinoma improved survival and
      reduced the risk of recurrent disease. The optimally staged group accounted for
      approximately 10% of women with Stage I disease. The role of adjuvant
      chemotherapy in optimally staged patients (especially those with good prognostic
      factors) has not been assessed adequately.

PMID- 15452837
TI  - Effects of prasterone on disease activity and symptoms in women with active
      systemic lupus erythematosus.
AB  - OBJECTIVE: To determine whether prasterone administration results in improvement
      or stabilization of systemic lupus erythematosus (SLE) disease activity and its
      symptoms. METHODS: Women with active SLE were treated with prasterone 200 mg/day
      plus standard SLE treatments or with placebo plus standard SLE treatments for up
      to 12 months in this randomized, double-blind investigation conducted at 27
      centers. Standard SLE treatments included prednisone (</=10 mg/day),
      antimalarials, and immunosuppressive agents; dosages were required to be stable
      for >/=6 weeks prior to enrollment and remain unchanged during protocol
      treatment. Responders were patients who experienced no clinical deterioration and
      had improvement or stabilization over the duration of the study in 2 disease
      activity measures (the SLE Disease Activity Index [SLEDAI] and the Systemic Lupus
      Activity Measure) and 2 quality of life measures (patient's global assessment and
      the Krupp Fatigue Severity Scale). RESULTS: A total of 381 women with SLE were
      enrolled. Among patients with clinically active disease at baseline (SLEDAI score
      >2), 86 of 147 in the prasterone group (58.5%) demonstrated improvement or
      stabilization without clinical deterioration, as compared with 65 of 146 in the
      placebo group (44.5%) (P = 0.017). Acne and hirsutism were reported in 33% and
      16%, respectively, of the prasterone group and in 14% and 2%, respectively, of
      the placebo group (P < 0.05 for both comparisons). However, most cases of acne
      and hirsutism were mild and did not require withdrawal from therapy. Myalgias and
      oral stomatitis were reported less frequently in the prasterone group (22% and
      15%, respectively) than in the placebo group (36% and 23%, respectively) (P <
      0.05 for both comparisons). Serum levels of high-density lipoprotein cholesterol,
      triglycerides, and C3 complement significantly decreased, while levels of
      testosterone and, to a lesser extent, estradiol increased in the prasterone
      group. CONCLUSION: In adult women with active SLE, administration of prasterone
      at a dosage of 200 mg/day improved or stabilized signs and symptoms of disease
      and was generally well tolerated.

PMID- 15452838
TI  - The keratins and their disorders.
AB  - Diseases caused by mutations in gene encoding keratin intermediate filaments (IF)
      are characterized by a loss of structural integrity in the cells expressing those
      keratins in vivo. This is manifested as cell fragility, compensatory epidermal
      hyperkeratosis, and keratin filament aggregation in some affected tissues.
      Keratin disorders are a novel molecular category including quite different
      phenotypes such as epidermolysis bullosa simplex (EBS), bullous congenital
      ichthyosiform erthroderma (BCIE), pachyonychia congenital (PC), steatocystoma
      multiplex, ichthyosis bullosa of Siemens (IBS), and white sponge nevus (WSN) of
      the orogenital mucosa.

PMID- 15452839
TI  - Multi-drug therapy in amyotrophic lateral sclerosis: combinations of multiple,
      untested drugs should not be used at this time.

PMID- 15452840
TI  - Multi-drug therapy in amyotrophic lateral sclerosis: the case for a multi-drug
      approach.

PMID- 15452841
TI  - Cardiac and skeletal muscle involvement in myotonic dystrophy type 2 (DM2): a
      quantitative 31P-MRS and MRI study.
AB  - In myotonic dystrophy type 2 (DM2/PROMM), cardiac muscle involvement is usually
      more benign than in DM1, but clinically severe cardiomyopathy has been reported
      in some patients. Using a novel method of magnetic resonance spectroscopy (MRS),
      we examined the left ventricular myocardium and the left gastrocnemius muscle in
      11 unselected DM2/PROMM patients without overt cardiac disease. Data on cardiac
      morphology and function were obtained by gradient echo two-dimensional cine
      magnetic resonance imaging (MRI); no significant differences were found between
      DM2 patients and healthy controls, but using a median split approach older
      patients showed mildly increased left ventricular (LV) volumes, i.e., 59%
      increase of end-systolic volume index (ESVI) and 35% increase of end-diastolic
      volume index (EDVI), and an increase of LV mass (26%). On cardiac MRS, DM2/PROMM
      patients showed a reduction of phosphocreatine (PCr) and adenosine triphosphate
      (ATP) by 25 and 20% compared to matched healthy controls. No significant
      differences were found between younger and older patients. In skeletal muscle of
      the DM2 patients, no significant decrease of PCr and ATP concentrations was
      found. However, in older patients, who commonly show overt hip flexor muscle
      weakness, we observed reduced values for PCr and ATP. Our MRS and MRI findings
      reveal evidence for subclinical cardiomyopathy in DM2/PROMM patients without
      overt heart disease. Future prospective studies are needed to clarify the risk of
      developing overt cardiac disease in DM2 and to define prognostic factors.

PMID- 15452842
TI  - Single motor unit variability with threshold stimulation in patients with
      amyotrophic lateral sclerosis and normal subjects.
AB  - Repetitive nerve stimulation often shows responses with an abnormal decrement in
      patients with amyotrophic lateral sclerosis (ALS), suggesting instability of the
      neuromuscular junction; however, the pathophysiology and response characteristics
      of this instability are not clear. We evaluated response variability of 47 single
      motor units from 16 patients with ALS and 51 units from 10 normal subjects,
      acquired by delivering threshold stimuli sporadically at 0.5 HZ or less. In
      addition, in 46 other different single motor units obtained from 21 patients with
      ALS, variability was studied at both 1- and 3-HZ stimulation rates. Motor units
      from patients with ALS were significantly more variable than those from normal
      subjects, even when their larger amplitude was accounted for. This increased
      variability was not rate dependent. Response variability is a critical measure in
      the statistical method of motor unit number estimation and is attributed to
      variability in the number of units activated; the fact that variability of single
      motor units varies with disease state may be a potentially confounding factor in
      the application of the technique.

PMID- 15452843
TI  - Brachial plexopathies: classification, causes, and consequences.
AB  - The brachial plexus, which is the most complex structure of the peripheral
      nervous system, supplies most of the upper extremity and shoulder. The high
      incidence of brachial plexopathies reflects its vulnerability to trauma and the
      tendency of disorders involving adjacent structures to affect it secondarily. The
      combination of anatomic, pathophysiologic, and neuromuscular knowledge with
      detailed clinical and ancillary study evaluations provides diagnostic and
      prognostic information that is important to clinical management. Since most
      brachial plexus disorders do not involve the entire brachial plexus but, rather,
      show a regional predilection, a regional approach to assessment of plexopathies
      is necessary.

PMID- 15452844
TI  - Degradation and metabolism of mometasone furoate in humans: influence of
      reversible, sequential metabolism, and ionic strength.

PMID- 15452845
TI  - Applications of model beta-hairpin peptides.
AB  - In recent years, beta-hairpin peptides have been studied in great detail. Much of
      the focus has been on the thermodynamic stability of beta-hairpin structure.
      Structural measurements have been conducted with nuclear magnetic resonance, with
      additional information obtained from circular dichroism, Fourier transform
      infrared, and molecular dynamic simulation studies. Point mutations, both in the
      beta-strands and in the turn region, have systematically explored the role of
      turn sequence, side-chain-side-chain interactions, intramolecular hydrogen
      bonding, and beta-strand length on beta-hairpin peptide conformational stability.
      In addition to studying the elements of structural stability independently, the
      cooperative nature of the individual components to combine to form the overall
      structure has also been investigated. Because the beta-hairpin peptides often
      spontaneously form their conformation, they have begun to serve as models for
      studying peptide binding and therapeutic agents.

PMID- 15452846
TI  - Alpha-1-acid glycoprotein directly affects the pharmacokinetics and the analgesic
      effect of methadone in the rat beyond protein binding.
AB  - Methadone is a basic drug highly bound to alpha1-acid glycoprotein (AGP), a
      plasma protein that increases in several pathological situations. Our aims were
      to evaluate the processes (pharmacokinetics-PK and/or pharmacodynamics-PD)
      associated with changes of methadone analgesia under conditions of increased AGP,
      and whether these changes are dependent on binding, secondary to a pathology, or
      directly attributable to AGP. AGP levels, in rats, were increased by two
      different methods: (a) experimental inflammation with turpentine oil (TP), and
      (b) by directly infusing the protein (exo-AGP). Both had a corresponding control
      group. Tail-flick analgesia and PK were evaluated after methadone dose (0.35
      mg/kg i.v.). Bicompartmental PK parameters as well as interanimal and assay
      variabilities were estimated using NONMEM. The relationship between Cp and
      analgesic effect (PD) was analyzed with WINNONLIN. AGP levels in both pretreated
      groups (TP and exo-AGP) were significantly increased, and the unbound fraction
      (fu) was decreased, compared to controls. All PK parameters were lower in the
      pretreated groups, but in exo-AGP the difference was maintained even when
      corrected by fu. Paradoxically, also in exo-AGP the analgesic effect was
      practically nonexistent, although the unbound Cp remained high, possibly
      associated to a change in the PD. AGP appears responsible for alterations in both
      PK and PD, beyond protein binding and inflammatory processes.

PMID- 15452847
TI  - [R,S]-Ethambutol dihydrochloride: variable-temperature studies of a dimorphic
      system with very similar packing.
AB  - The two polymorphs (Forms I and II) of [R,S]-ethambutol dihydrochloride transform
      enantiotropically and reversibly in a single-crystal-to-single-crystal phase
      transformation mode. These structurally very similar forms have been
      characterized and their thermodynamic relationship has been investigated by
      variable-temperature solid-state carbon-13 nuclear magnetic resonance, variable
      temperature powder X-ray diffraction, differential scanning calorimetry, and
      optical microscopy. The nuclear magnetic resonance results are compared with
      those for the two polymorphs of the [S,S] diastereomer with known structures.

PMID- 15452848
TI  - Ca2+ influx into identified leech neurons induced by 5-hydroxytryptamine.
AB  - The role of 5-hydroxytryptamine (5-HT, serotonin) in the control of leech
      behavior is well established and has been analyzed extensively on the cellular
      level; however, hitherto little is known about the effect of 5-HT on the
      cytosolic free calcium concentration ([Ca(2+)](i)) in leech neurons. As
      [Ca(2+)](i) plays a pivotal role in numerous cellular processes, we investigated
      the effect of 5-HT on [Ca(2+)](i) (measured by Fura-2) in identified leech
      neurons under different experimental conditions, such as changed extracellular
      ion composition and blockade of excitatory synaptic transmission. In pressure
      (P), lateral nociceptive (N1), and Leydig neurons, 5-HT induced a [Ca(2+)](i)
      increase which was predominantly due to Ca(2+) influx since it was abolished in
      Ca(2+)-free solution. The 5-HT-induced Ca(2+) influx occurred only if the cells
      depolarized sufficiently, indicating that it was mediated by voltage-dependent
      Ca(2+) channels. In P and N1 neurons, the membrane depolarization was due to
      Na(+) influx through cation channels coupled to 5-HT receptors, whereby the dose
      dependency suggests an involvement in excitatory synaptic transmission. In Leydig
      neurons, 5-HT receptor-coupled cation channels seem to be absent. In these cells,
      the membrane depolarization activating the voltage-dependent Ca(2+) channels was
      evoked by 5-HT-triggered excitatory glutamatergic input. In Retzius, anterior
      pagoda (AP), annulus erector (AE), and median nociceptive (N2) neurons, 5-HT had
      no effect on [Ca(2+)](i).

PMID- 15452849
TI  - Segment-specific muscle degeneration is triggered directly by a steroid hormone
      during insect metamorphosis.
AB  - During metamorphosis of the hawkmoth, Manduca sexta, some larval muscles
      degenerate while others are respecified for new functions. In larvae, accessory
      planta retractor muscles (APRMs) are present in abdominal segments 1 to 6 (A1 to
      A6). APRMs serve as proleg retractors in A3 to A6 and body wall muscles in A1 and
      A2. At pupation, all APRMs degenerate except those in A2 and A3, which are
      respecified to circulate hemolymph in pupae. The motoneurons that innervate
      APRMs, the APRs, likewise undergo segment-specific programmed cell death (PCD),
      as a direct, cell-autonomous response to the prepupal peak of ecdysteroids. The
      segment-specific patterns of APR and APRM death differ. The present study tested
      the hypothesis that APRM death is a direct, cell-autonomous response to the
      prepupal peak of ecdysteroids. Prevention of the prepupal peak prevented APRM
      degeneration, and replacement of the peak by infusion of 20-hydroxyecdysone
      restored the correct segment-specific pattern of APRM degeneration. Surgical
      denervation of APRMs did not perturb their segment-specific degeneration at
      pupation, indicating that signals from APRs are not required for the muscles'
      segment-specific responses to ecdysteroids. The possibility that instructive
      signals originate from APRMs' epidermal attachment points was tested by treating
      the epidermis with a juvenile hormone analog to prevent pupal development. This
      manipulation likewise did not alter APRM fate. We conclude that both the muscles
      and motoneurons in this motor system respond directly and cell-autonomously to
      prepupal ecdysteroids to produce a segment-specific pattern of PCD that is
      matched to the functional requirements of the pupal body.

PMID- 15452850
TI  - Opiate modulation of monoamines in the chick forebrain: possible role in
      emotional regulation?
AB  - Numerous studies have shown that the opiate system is crucially involved in
      emotionally guided behavior. In the present study, we focussed on the medio
      rostral neostriatum/hyperstriatum ventrale (MNH) of the chick forebrain. This
      avian prefrontal cortex analogue is critically involved in auditory filial
      imprinting, a well-characterized juvenile emotional learning event. The high
      density of mu-opiate receptors expressed in the MNH led to the hypothesis that mu
      opiate receptor-mediated processes may modulate the glutamatergic, dopaminergic,
      and/or serotonergic neurotransmission within the MNH and thereby have a critical
      impact on filial imprinting. Using microdialysis and pharmaco-behavioral
      approaches in young chicks, we demonstrated that: the systemic application of the
      mu-opiate receptor antagonist naloxone (5, 50 mg/kg) significantly increased
      extracellular levels of 5-HIAA and HVA; the systemic application of the specific
      mu-opiate receptor agonist DAGO (5 mg/kg) increased the levels of HVA and
      taurine, an effect that was antagonized by simultaneously applied naloxone (5
      mg/kg); the local application of DAGO (1 mM) had no effects on 5-HIAA, HVA,
      glutamate, and taurine, however, the effects of systemically injected naloxone (5
      mg/kg) were abolished by simultaneously applied DAGO (1 mM); the systemic
      application of naloxone (5 mg/kg) increased distress behavior (measured as the
      duration of distress vocalization during separation from the peer group). These
      results are in line with our hypothesis that the mu-opiate receptor-mediated
      modulation of serotonergic and dopaminergic neurotransmission alters the
      emotional and motivational status of the animal and thereby may play a modulatory
      role during filial imprinting in the newborn animal.

PMID- 15452851
TI  - Growth cones turn and migrate up an immobilized gradient of the laminin IKVAV
      peptide.
AB  - Growth cone navigation is guided by extrinsic environmental proteins, called
      guidance cues. Many in vitro studies have characterized growth cone turning up
      and down gradients of soluble guidance cues. Although previous studies have shown
      that axonal elongation rates can be regulated by gradients of surface-bound
      molecules, there are no convincing demonstrations of growth cones turning to
      migrate up a surface-bound gradient of an adhesive ligand or guidance cue. In
      order to test this mode of axonal guidance, we used a photo-immobilization
      technique to create grids and gradients of an adhesive laminin peptide on
      polystyrene culture dish surfaces. Chick embryo dorsal root ganglia (DRGs) were
      placed on peptide grid patterns containing surface-bound gradients of the IKVAV
      containing peptide. DRG growth cones followed a path of surface-bound peptide to
      the middle of a perpendicularly oriented gradient with a 25% concentration
      difference across 30 microm. The majority of growth cones turned and migrated up
      the gradient, turning until they were oriented directly up the gradient. Growth
      cones slowed their migration when they encountered the gradient, but growth cone
      velocity returned to the previous rate after turning up or down the gradient.
      This resembles in vivo situations where growth cones slow at a choice point
      before changing the direction of axonal extension. Thus, these results support
      the hypothesis that mechanisms of axonal guidance include growth cone orientation
      by gradients of surface-bound adhesive molecules and guidance cues.

PMID- 15452852
TI  - Cellular and molecular characterization of early and late retinal stem
      cells/progenitors: differential regulation of proliferation and context dependent
      role of Notch signaling.
AB  - Retinal stem cells/progenitors that define the evolutionarily conserved early and
      late stages of retinal histogenesis are known to have distinct competence to give
      rise to stage-specific retinal cell types. However, the information regarding
      their innate proliferative behavior and phenotypic potential in terms of
      generating neurons and glia is lacking. Here we demonstrate that, like their
      counterparts in other central nervous system (CNS) regions during early and late
      stages of embryonic development, the early and late retinal stem
      cells/progenitors display different proliferative response to fibroblast growth
      factor 2 (FGF2) and epidermal growth factor (EGF) and bias towards generating
      neurons or glia. Although the former predominantly generate neurons, the latter
      are partial towards giving rise to glia. Transcription profiling identified
      classes of genes that are differentially expressed in early and late retinal stem
      cells/progenitors in proliferating conditions and suggested that the distinct
      proliferative response to FGF2 and EGF is likely due to differential expression
      of FGF receptor 1 (FGFR1) and EGF receptor (EGFR). However, the proliferative
      maintenance of retinal stem cells/progenitors is likely to include other
      signaling pathways such as those mediated by insulin-like growth factors (IGFs)
      and stem cell factor (SCF). Transcription profiling of early and late retinal
      stem cells/progenitors in proliferating and differentiating conditions suggested
      a context dependent role for Notch signaling, which may constitute one of the
      mechanisms underlying the stage-dependent phenotypic potential of retinal stem
      cells/progenitors.

PMID- 15452853
TI  - Fine-structural analysis and connexin expression in the retina of a transgenic
      model of Huntington's disease.
AB  - Recent studies indicate that the visual system appears more frequently affected
      in polyglutamine diseases than expected previously. Here, we investigated retinal
      degenerations in adult transgenic R6/2 mice, a model for Huntington's disease
      (HD). Light microscopical analysis revealed retinal dystrophy all over the
      retina, with central areas showing major effects. Electron microscopical analysis
      showed strong degenerations of outer and inner photoreceptor segments, shrinkage
      of photoreceptor cell somata, and signs of degeneration in photoreceptor
      terminals in the outer plexiform layer. Terminal deoxynucleotidyl transferase
      mediated dUTP nick end labeling showed hints of apoptosis. Mutant huntingtin and
      ubiquitin were expressed in all classes of retinal neurons, the pigment
      epithelium, and to a minor extent in neuropil structures. For investigating
      possible links to functional impairments in the rod-cone pathway, expression
      levels of three connexins (Cx) were compared in R6/2 and wildtype mice retinae.
      In R6/2 mice, expression of Cx36, the major neuronal connexin in the retina, was
      slightly reduced in the outer plexiform layer, indicating affected photoreceptor
      terminals as detected at the electron microscopical level. In contrast, Cx45, a
      putative neuronal connexin in the retina, was remarkably reduced in the inner
      plexiform layer of R6/2 mice. This result corresponded to fainter signals of Cx45
      mRNA as documented by in situ hybridization and to a lower level of mCx45 cDNA as
      obtained by polymerase chain reaction after reverse transcription, suggesting
      functional deficits in spatial processing of Cx45-mediated gap junction coupling
      due to transgene-induced retinal degenerations. Thus, it is important to clarify
      the meaning of visual involvement in HD.

PMID- 15452854
TI  - Experience-dependent activation of extracellular signal-related kinase (ERK) in
      the olfactory bulb.
AB  - Protein kinase-mediated signaling cascades play a fundamental role in translating
      extracellular signals into cellular responses in CNS neurons. The mitogen
      activated protein kinase / extracellular signal-regulated kinase (MAPK/ERK)
      pathway participates in regulating diverse neuronal processes such as
      proliferation, differentiation, survival, synaptic efficacy, and long-term
      potentiation by inducing cAMP-response element (CRE)-mediated gene transcription.
      Central olfactory structures show plasticity throughout the lifespan, but the
      role of the MAPK/ERK pathway in odor-evoked activity has yet to be determined.
      Therefore, we examined the effect of odorant exposure and early postnatal
      deprivation on ERK activity. We found that odor stimulation induced ERK
      phosphorylation, that activation of the ERK pathway was decreased with early
      postnatal deprivation, and that ERK phosphorylation was subsequently increased by
      restoring stimulation. Further, locations of ERK activation in bulbar neurons
      after exposure to single odorants corresponded to odor-evoked activity patterns
      found with other measures of activity in the bulb. Finally, due to the
      cytoplasmic location of pERK, activated dendrites belonging to the primary
      excitatory output neurons of the bulb were observed following a single odor
      exposure. The results indicate that the MAPK/ERK pathway is activated by odorant
      stimulation and may play an important role in developmental sensory plasticity in
      the olfactory bulb.

PMID- 15452855
TI  - Expression of dopamine and vesicular monoamine transporters and differential
      vulnerability of mesostriatal dopaminergic neurons.
AB  - Numerous studies suggest that the dopamine transporter (DAT), responsible for
      dopamine reuptake, may act as a vulnerability factor in the pathogenesis of
      Parkinson's disease (PD) and the vesicular monoamine transporter (VMAT2),
      responsible for its vesicular storage, as a neuroprotective factor. However, the
      relevance of each on the differential vulnerability of midbrain DA cells remains
      unknown. Here we studied the relationship between the expression pattern (mRNA
      and protein) of both transporters and the differential vulnerability of midbrain
      DA cells in a model of PD (intracerebroventricular injection of 6-OHDA in rats)
      and in monkey and human midbrain. Our results revealed that the expression
      patterns for VMAT2 mRNA and protein and DAT mRNA are similar, with the highest
      levels in the rostromedial region of substantia nigra (SNrm), followed by the
      caudoventral region of SN (SNcv), the ventral tegmental area and pigmented
      parabrabraquial nucleus (VTA/PBP), and finally the linear and interfascicular
      nuclei (Li/IF). In contrast, the expression of DAT protein in rats, monkeys, and
      humans followed a caudoventrolateral-to-rostrodorsomedial decreasing gradient
      (SNcv > SNrm > VTA/PBP > Li/IF), matching the degeneration profile observed after
      intracerebroventricular injection of 6-OHDA and in PD. In addition, DAT blockade
      made all midbrain DA cells equally resistant to 6-OHDA. These data indicate that
      DAT protein levels, but not DAT mRNA levels, are closely related to the
      differential vulnerability of midbrain DA cells and that this relationship is
      unaffected by the relative levels of VMAT2. Furthermore, the difference between
      DAT mRNA and protein profiles suggests internuclear differences in its
      posttransductional regulation.

PMID- 15452856
TI  - Expression of Cux-1 and Cux-2 in the subventricular zone and upper layers II-IV
      of the cerebral cortex.
AB  - Little is known about how neurons in the different layers of the mammalian
      cerebral cortex are specified at the molecular level. Expression of two
      homologues of the Drosophila homeobox Cut gene, Cux-1 and Cux-2, is strikingly
      specific to the pyramidal neurons of the upper layers (II-IV) of the murine
      cortex, suggesting that they may define the molecular identity of these neurons.
      An antibody against Cux-1 labels the nucleus of most of the postmitotic upper
      layer neurons but does not label parvoalbumin-positive cortical interneurons that
      derive from the medial ganglionic eminence. Cux-1 and Cux-2 represent early
      markers of neuronal differentiation; both genes are expressed in postmitotic
      cortical neurons from embryonic stages to adulthood and in the proliferative
      regions of the developing cortex. In precursors cells, Cux-1 immunoreactivity is
      weak and diffuse in the cytoplasm and nucleus of ventricular zone (VZ) cells,
      whereas it is nuclear in the majority of bromodeoxyuridine (BrdU)-positive
      subventricular zone (SVZ) dividing cells, suggesting that Cux-1 function is first
      activated in SVZ cells. Cux-2 mRNA expression is also found in the embryonic SVZ,
      overlapping with BrdU-positive dividing precursors, but it is not expressed in
      the VZ. A null mutation in Pax-6 disrupts Cux-2 expression in the SVZ and Cux-1
      and Cux-2 expression in the postmigratory cortical neurons. Thus, these data
      support the existence of an intermediate neuronal precursor in the SVZ dedicated
      to the generation of upper layer neurons, marked specifically by Cux-2. The
      patterns of expression of Cux genes suggest potential roles as determinants of
      the neuronal fate of the upper cortical layer neurons.

PMID- 15452857
TI  - Expression patterns of basic helix-loop-helix transcription factors define
      subsets of olfactory progenitor cells.
AB  - Direct damage to the olfactory epithelium by inhalation of the olfactotoxin
      methyl bromide activates a population of multipotent globose basal cells, which
      reconstitute all depleted cell populations. Because members of the basic helix
      loop-helix family of transcription factors are known to regulate neurogenesis and
      cell production, we performed in situ hybridization to examine the expression of
      several members of that family during the recovery of the rat olfactory
      epithelium after methyl bromide lesion. The numbers of basal cells expressing the
      proneural transcriptional activators Mash1, Neurogenin1, and NeuroD all fall
      precipitously 1 day after lesion. Mash1 levels begin to recover by 2 days,
      Neurogenin1 and NeuroD by 3 days, and substantial numbers of neurons reappear by
      4 days. The antineurogenic factor Hes1 is limited to the sustentacular cells of
      the unlesioned olfactory epithelium and to the adjoining respiratory epithelium.
      Immediately after methyl bromide lesion, but not at any time after bulbectomy, a
      large fraction of residual, marker-confirmed globose basal cells initiate
      expression of Hes1. Subsequently, the Hes1-positive cells lose their association
      with the basal lamina, shift apically, and differentiate into sustentacular
      cells. In contrast, Hes5 is expressed by a small subset of globose basal cells
      and by olfactory ensheathing glia in the normal mucosa; Hes5 label disappears
      from both transiently after lesion. In sum, the recovery of the neuronal
      population after peripheral lesion recapitulates the sequence of transcription
      factor expression observed during embryonic development of the epithelium.
      Moreover, expression of Hes1 marks that population of globose basal cells
      committed to making sustentacular cells after methyl bromide lesion.

PMID- 15452858
TI  - Separation and determination of two sesquiterpene lactones in Radix inulae and
      Liuwei Anxian San by microemulsion electrokinetic chromatography.
AB  - A novel microemulsion electrokinetic chromatography (MEEKC) method for separating
      and determining two sesquoterpene lactones, alantolactone (AL) and
      isoalantolactone (IAL), in Radix inulae and Liuwei Anxian San has been developed.
      The effects of several important factors such as internal organic phases,
      concentration of microemulsion, concentration of acetonitrile, injection time and
      running voltage were systematically investigated to determine the optimum
      conditions. The optimum microemulsion system was composed of n-hexane (0.32%
      w/w), SDS (1.24% w/w), 1-butanol (2.64% w/w), acetonitrile (10% w/w) and 10 mm
      sodium tetraborate buffer (85.80% w/w, pH 9.2). The applied voltage was 20 kV.
      The analytes were detected at 214 nm. Regression equations revealed linear
      relationships (correlation coefficients 0.9950 for AL and 0.9946 for IAL) between
      the peak area of each analyte and the concentration. The limits of detection
      (defined as a signal-to-noise ratio of about 3) were approximately 0.45 microg/mL
      for AL and 0.56 microg/mL for IAL. The levels of the analytes were successfully
      determined with recoveries ranging from 98.2 to 104.3%. Furthermore, a simple and
      effective extraction method, with methanol in an ultrasonic water bath for 60
      min, was used for sample preparing. Also, MEEKC was compared with micellar
      electrokinetic chromatography (MEKC) and shown better separation results.

PMID- 15452859
TI  - Genetics of pigmentary disorders.
AB  - The genetic and molecular bases of various types of congenital pigmentary
      disorders have been classified in the past 10 years, as follows: (1) disorders of
      melanoblast migration in the embryo from the neural crest to the skin:
      piebaldism; Waardenburg syndrome 1-4 (WS1-WS4); dyschromatosis symmetrica
      hereditaria. (2) Disorders of melanosome formation in the melanocyte: Hermansky
      Pudlak syndrome 1-7 (HPS1-7); Chediak-Higashi syndrome 1 (CHS1). (3) Disorders of
      melanin synthesis in the melanosome: oculocutaneous albinism 1-4 (OCA1-4). (4)
      Disorders of mature melanosome transfer to the tips of the dendrites Griscelli
      syndrome 1-3 (GS1-3). These disorders are presented and their gene mutations and
      pathogenesis are discussed.

PMID- 15452860
TI  - Molecular genetics of the ichthyoses.
AB  - The ichthyoses are a large, clinically, genetically, and etiologically
      heterogeneous group of disorders of cornification due to abnormal differentiation
      and desquamation of the epidermis. Although they differ in clinical features,
      inheritance, and structural and biochemical abnormalities of the epidermis, they
      often pose a diagnostic challenge. For each of the 12 ichthyoses and related
      disorders described here, the major disease genes have been identified and
      genotype-phenotype correlation have begun to emerge. The molecular findings
      reveal the functional importance and interactions of many different epidermal
      proteins and metabolic pathways, including major structural proteins (keratins,
      loricrin), enzymes involved in lipid metabolism (transglutaminase 1,
      lipoxygenases, fatty aldehyde dehydrogenase, steroid sulfatase,
      glucocerebrosidase, Delta8-Delta7 sterol isomerase, 3beta-hydroxysteroid
      dehydrogenase), and protein catabolism (LEKTI), peroxisomal transport and
      processing (Peroxin 7 receptor, Phytanoyl-CoA hydroxylase) and DNA repair
      (proteins of the transcription repair complex). This review highlights the
      spectacular advances in the molecular genetics and biology of heritable
      ichthyoses over the past decade. It illustrates the power of molecular
      diagnostics for refining disease classification, providing prenatal diagnosis,
      improving genetic counseling, and clinical management.

PMID- 15452861
TI  - Enantioselective conjugate addition of dialkylzinc and diphenylzinc to enones
      catalyzed by a chiral copper(I) binaphthylthiophosphoramide or
      binaphthylselenophosphoramide ligand system.
AB  - The enantioselective conjugate addition of dialkylzinc or diphenylzinc to enones
      was catalyzed by a copper(I)-axially chiral binaphthylthiophosphoramide or
      binaphthylselenophosphoramide ligand system at room temperature (20 degrees C) or
      0 degrees C, affording the Michael adducts in high yields with excellent ee for
      cyclic and acyclic enones. The enantioselectivity and reaction rate achieved here
      are one of the best results yet for the Cu-catalyzed conjugate addition to
      enones. It was revealed that this series of chiral phosphoramides was a novel
      type of S,N-bidentate ligands on the basis of (31)P NMR and (13)C NMR
      spectroscopic investigations. The mechanism of this asymmetric conjugate addition
      system has been investigated as well. We found that the acidic proton of
      phosphoramide in these chiral ligands play a significant role in the formation of
      the active species. A bimetallic catalytic process has been proposed on the basis
      of previous literature. The linear effect of product ee and ligand ee further
      revealed that the active species is a monomeric Cu(I) complex bearing a single
      ligand [Cu(I):ligand 1:1].

PMID- 15452862
TI  - Electron spin resonance spectroscopy reveals alpha-phenyl-N-tert-butylnitrone
      spin-traps free radicals in rat striatum and prevents haloperidol-induced vacuous
      chewing movements in the rat model of human tardive dyskinesia.
AB  - The typical antipsychotic drug haloperidol causes vacuous chewing movements (VCM)
      in rats, which are representative of early-Parkinsonian symptoms or later-onset
      extrapyramidal side effects of tardive dyskinesia (TD) in humans. Haloperidol
      (HP) has been hypothesized to potentiate increases in oxidative stress or free
      radical-mediated levels of toxic metabolites in rat striatum while simultaneous
      upregulating dopamine (DA)-D2 receptors leading to presumed DA supersensitivity.
      Alpha(alpha)-Phenyl-N-tert-butylnitrone (PBN) is an antioxidant used to combat
      oxidative stress and measure increases in PBN spin-adduct activity. Thus, the aim
      of this study was to investigate whether VCMs are related to upregulation of DA
      D2 receptors or to increased levels of free radicals produced during oxidative
      stress, and whether PBN had any protective effects. Rats received daily chronic
      (28 day) i.p. injections of saline, haloperidol (2 mg/kg), PBN (150 mg/kg), or
      haloperidol + PBN. The VCM model was used to measure extrapyramidal side effects
      of drug treatments. Electron spin resonance (ESR) spectroscopy was performed to
      compare concentrations of free radical species in rats receiving injections of HP
      + PBN. To examine the upregulation of DA-D2 receptors, binding assays were
      carried out to assess the increase in DA-D(2) receptor numbers with respect to
      VCMs following treatment of rats injected with HP, PBN, and HP + PBN. Results of
      these experiments show that HP-induced VCMs in rats results from increases in
      oxidative cellular events and may not be related to increases in striatal DA-D(2)
      receptors.

PMID- 15452863
TI  - Differences in the cellular distribution of D1 receptor mRNA in the hippocampus
      of bipolars and schizophrenics.
AB  - Several lines of evidence have pointed to a role of the dopamine system in the
      pathophysiology of schizophrenia. A recent postmortem study demonstrated a
      selective decrease of tyrosine hydroxylase fibers on pyramidal neurons in sector
      CA2 in the hippocampus of schizophrenics. Although both brain imaging and
      postmortem studies have examined the distribution of the D1 receptor in the
      prefrontal and cingulate cortex, no study to date has examined its expression of
      mRNA using a high-resolution autoradiographic approach. In order to further
      assess whether the regulation of the dopamine D1 receptor is altered in
      hippocampal neurons in this disorder, we used in situ hybridization (ISH) to
      measure the expression of messenger RNA for this receptor in the dentate gyrus
      and sectors CA1-4. Both the number of cells expressing D1 mRNA and the amount of
      expression per cell were measured in 15 schizophrenic, 15 bipolar disorder, and
      15 normal control subjects. The results show a significant (21%) and selective
      decrease in D1 mRNA expression in sector CA3 of schizophrenic subjects. First
      degree relatives of schizophrenics did not show any differences in either the
      expression of D1 mRNA per cell or the number of cells expressing this mRNA when
      compared to a separate group of normal controls matched for age and PMI. Subjects
      with bipolar disorder also showed a significant (25%) and selective increase of
      D1 mRNA expression in sector CA2. Other hippocampal sectors did not show
      significant changes. These findings in schizophrenics and bipolars were also
      associated with inverse changes in the overall number of neurons expressing D1
      mRNA in sectors CA3 and CA2, respectively. This study shows diagnosis-specific
      changes in D1 mRNA expression in the hippocampus of schizophrenic versus bipolar
      subjects and suggests that this neuromodulatory system may show distinct changes
      in the pathophysiology of the two disorders.

PMID- 15452864
TI  - L-arginine increases dopamine transporter activity in rat striatum via a nitric
      oxide synthase-dependent mechanism.
AB  - Literature reports suggest that nitric oxide (NO) participates in the regulation
      of dopaminergic neurotransmission, possibly through interaction with cysteine
      residues of the dopamine transporter (DAT). Rotating disk electrode voltammetry
      was used to measure dopamine (DA) transport in rat striatum to determine if 1)
      the nitric oxide synthase (NOS) substrate, L-arginine (L-Arg), could affect DAT
      activity; 2) L-Arg-dependent effects on DAT activity could be blocked by NOS and
      guanylate cyclase inhibitors, a NO scavenger, DA, and cocaine; 3) a NO donor
      could affect DAT activity; and 4) L-Arg could protect the DAT from a sulfhydryl
      agent. L-Arg increased DAT activity by increasing V(max). NOS inhibitors (S
      ethylisothiourea and S-isopropylisothiourea), a NO scavenger (2-(4-carboxyphenyl)
      4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide), DA, and cocaine blocked the L-Arg
      effect. The guanylate cyclase inhibitor, 1H-(1,2,4)-oxadiazolo[4,3a]quinoxalin-1
      one, did not. The NO donor, S-nitroso-N-acetylpenicillamine, decreased DAT
      activity and L-Arg protected the DAT from the effects of the sulfhydryl agent N
      ethylmaleimide. These results suggest that L-Arg, via NO, may play a role in
      regulating DAT activity in rat striatum by increasing the V(max) of DA transport.
      Furthermore, it is suggested that the effects of L-Arg on DAT activity may be due
      to modification of the DAT itself, possibly via the NO-mediated modification of
      DAT cysteine residues. Finally, NO produced from L-Arg may affect the DAT
      differently than NO from NO donors. These results further the notion that
      dopaminergic neurotransmission may be regulated by changes in DAT activity caused
      by L-Arg and NOS.

PMID- 15452865
TI  - Role of locus coeruleus alpha1-adrenoceptors in motor activity in rats.
AB  - The question of whether or not the locus coeruleus (LC) participates in the
      control of motor activity has been controversial due to difficulties in
      demonstrating permanent motor deficits after neurotoxic lesions of this nucleus
      or of the dorsal noradrenergic bundle (DNB). In the present experiments it was
      shown in rats that acute local blockade (with terazosin) or stimulation (with
      phenylephrine) of LC alpha(1)-adrenoceptors respectively blocked or stimulated
      exploratory behavior in a novel cage and the home cage. Moreover, previous lesion
      of the DNB by i.p. DSP4 abolished the behavioral changes to local LC alpha(1)
      receptor manipulation but did not affect motor activity in the novel or home cage
      by itself. These findings are consistent with the hypothesis that the intact LC
      does contribute to motor activity control, exerted in part by its alpha(1)
      receptors; however, the permanent loss of this nucleus is compensated for by
      remaining CNS motor structures.

PMID- 15452866
TI  - Effects of birth insult and stress at adulthood on excitatory amino acid
      receptors in adult rat brain.
AB  - Birth complications involving fetal hypoxia and stress at adulthood, which are
      risk factors for schizophrenia, can produce alterations in subcortical dopamine
      (DA) function in rat models. As adults, rats born either by cesarean section (C
      section) or by C-section with added global anoxia show increased stress-induced
      DA release from nucleus accumbens and increased amphetamine-induced locomotion,
      compared to vaginally born controls. Moreover, stress at adulthood interacts with
      these birth insults to modulate DA receptor and transporter levels. Glutamatergic
      transmission at the level of the nucleus accumbens, prefrontal cortex, and
      hippocampus are known to modulate subcortical DA activity. Thus, altered
      excitatory amino acid (EAA) function might contribute to the dopaminergic changes
      observed in rats after birth insult and/or stress at adulthood. To test this
      possibility, rats born vaginally, by C-section, or by C-section with 15 min of
      anoxia, were either repeatedly stressed (15 min of tail pinch daily for 5 days)
      at adulthood or received no stress, and levels of EAA receptor binding were
      measured by ligand autoradiography in limbic brain regions. As adults, rats born
      by C-section showed increases in AMPA receptor binding in nucleus accumbens
      shell, NMDA receptor binding in cingulate cortex, and kainate receptor binding in
      the hippocampal CA1 region. Anoxic rats showed increases in CA1 kainate receptor
      and anterior olfactory NMDA receptor binding. Stress at adulthood increased AMPA
      receptor binding in several regions of prefrontal cortex and reduced NMDA
      receptor binding in infralimbic cortex and dentate gyrus, across all birth
      groups. Two instances of interactions between birth insult and stress at
      adulthood were observed. Stress reduced cingulate cortex NMDA receptor binding
      and increased olfactory tubercle kainate receptor binding only in C-sectioned
      animals, but not in controls. The possibility that the observed EAA receptor
      changes contribute to dopaminergic dysfunction in these animal models is
      discussed, in light of known glutamate-DA interactions.

PMID- 15452867
TI  - Cortical dopamine D2 receptors in type 1 and 2 alcoholics measured with human
      whole hemisphere autoradiography.
AB  - Alcoholism has been associated with lower density of striatal dopamine (DA) D(2)
      receptors, but there is much less data on cortical DA D(2) receptors. We
      evaluated the [(125)I]epidepride binding to DA D(2) receptors in Cloninger type 1
      and 2 alcoholics and controls in frontal, temporal, and anterior cingulate
      cortices by using human postmortem whole hemispheric autoradiography, which
      provides high-resolution images corresponding to positron emission tomographic
      (PET) studies. Type 1 alcoholics had lower and type 2 alcoholics had higher DA
      D(2) receptor density in all cortical areas compared to controls. Although the
      results did not reach statistical significance, the effect sizes were high. The
      DA D(2) receptor density in type 2 alcoholics decreased statistically
      significantly with age, and after correcting for age the binding values also fell
      below the level of controls. A statistically non-significant tendency towards a
      decrease of cortical DA D(2) receptors was seen in controls, whereas in the type
      1 alcoholic group no consistent correlation or even tendency towards increase
      with age was observed. Our results give preliminary evidence that DA D(2)
      receptors in cortical areas may be lower among both groups of alcoholics, but not
      necessarily of same magnitude as in subcortical structures. The rapid decline of
      cortical DA D(2) receptors among type 2 alcoholics may have some relevance to
      their antisociality, because this trait tends to diminish with age. The absence
      of correlation or even tendency towards increase of cortical DA D(2) receptors
      with age seen in type 1 alcoholics may give further evidence that they have a pre
      existing dopaminergic deficit. However, these results especially regarding aging
      effect must be considered as preliminary due to the different age-range of type 2
      alcoholics compared to two other groups.

PMID- 15452868
TI  - Development and validation of the Unified Multiple System Atrophy Rating Scale
      (UMSARS).
AB  - We aimed to develop and validate a novel rating scale for multiple system atrophy
      (Unified Multiple System Atrophy Rating Scale-UMSARS). The scale comprises the
      following components: Part I, historical, 12 items; Part II, motor examination,
      14 items; Part III, autonomic examination; and Part IV, global disability scale.
      For validation purposes, 40 MSA patients were assessed in four centers by 4
      raters per center (2 senior and 2 junior raters). The raters applied the UMSARS,
      as well as a range of other scales, including the Unified Parkinson's Disease
      Rating Scale (UPDRS) and the International Cooperative Ataxia Rating Scale
      (ICARS). Internal consistency was high for both UMSARS-I (Crohnbach's alpha =
      0.84) and UMSARS-II (Crohnbach's alpha = 0.90) sections. The interrater
      reliability of most of the UMSARS-I and -II items as well as of total UMSARS-I
      and -II subscores was substantial (k(w) = 0.6-0.8) to excellent (k(w) > 0.8).
      UMSARS-II correlated well with UPDRS-III and ICARS (rs > 0.8). Depending on the
      degree of the patient's disability, completion of the entire UMSARS took 30 to 45
      minutes. Based on our findings, the UMSARS appears to be a multidimensional,
      reliable, and valid scale for semiquantitative clinical assessments of MSA
      patients.

PMID- 15452869
TI  - Transgenic expression of Cre recombinase from the tyrosine hydroxylase locus.
AB  - Catecholaminergic neurons are affected in several neurological and psychiatric
      diseases. Tyrosine hydroxylase (TH) is the first, rate-limiting enzyme in
      catecholamine synthesis. We report a knockin mouse expressing Cre-recombinase
      from the 3'-untranslated region of the endogenous Th gene by means of an internal
      ribosomal entry sequence (IRES). The resulting Cre expression matches the normal
      pattern of TH expression, while the pattern and level of TH are not altered in
      the knockin mouse. Crossings with two different LacZ reporter mice demonstrated
      Cre-mediated genomic recombination in TH expressing tissues. In addition, LacZ
      was found in some unexpected cell populations (including oocytes), indicating
      recombination due to transient developmental TH expression. Our novel knockin
      mouse can be used for generation of tissue-specific or general knockouts
      (depending on scheme of crossing) in mice carrying genes flanked by loxP sites.
      This knockin mouse can also be used for tracing cell lineages expressing TH
      during development.

PMID- 15452870
TI  - Mouse zinc transporter 1 gene provides an essential function during early
      embryonic development.
AB  - The SLC30 family of cation diffusion transporters includes at least nine members
      in mammals, most of which have been documented to play a role in zinc transport.
      The founding member of this family, Znt1, was discovered by virtue of its ability
      to efflux zinc from cells and to protect them from zinc toxicity. However, its
      physiological functions remain unknown. To address this issue, mice with targeted
      knockout of the Znt1 gene were generated by homologous recombination in embryonic
      stem cells. Heterozygous Znt1 mice were viable. In contrast, homozygous Znt1 mice
      died in utero soon after implantation due to a catastrophic failure of embryonic
      development. Although extraembryonic membranes formed around these embryos, the
      embryo proper failed to undergo morphogenesis past the egg cylinder stage and was
      amorphous by d9 of pregnancy. Expression of the Znt1 gene was detected
      predominantly in trophoblasts and in the maternal deciduum during the
      postimplantation period (d5 to d8). The failure of homozygous Znt1 embryos to
      develop could not be rescued by manipulating maternal dietary zinc (either excess
      or deficiency) during pregnancy. However, embryos in Znt1 heterozygous females
      were approximately 3 times more likely to develop abnormally when exposed to
      maternal dietary zinc deficiency during later pregnancy than were those in
      wildtype females. These studies suggest that Znt1 serves an essential function of
      transporting maternal zinc into the embryonic environment during the egg cylinder
      stage of development, and further suggest that Znt1 plays a role in zinc
      homeostasis in adult mice.

PMID- 15452871
TI  - Generation of a conditional allele of the CBP gene in mouse.
AB  - CREB-binding protein (CBP) is an important transcriptional cofactor for various
      intracellular signaling pathways, including Ca(2+)- and cAMP-mediated gene
      activation. The loss of one CBP allele causes the human Rubinstein-Taybi
      syndrome, which is characterized by mental retardation and other severe
      developmental defects. Deletion of both CBP alleles in the mouse leads to early
      embryonic lethality. To address the function of CBP in late embryogenesis and in
      adult physiology, a floxed CBP allele (CBP(fl)) was generated. Using the Cre/loxP
      recombination system, CBP function was disrupted in principal forebrain neurons
      by breeding with a transgenic CaMKIIalpha-Cre mouse line to obtain
      CBP(fl/fl;CaMKIIalphaCre) mice. These mice contain CBP(stop523) alleles
      specifically in principal forebrain neurons, presumably resulting in the
      production of a truncated CBP protein unable to interact with a number of
      transcription factors, including phosphorylated CREB.

PMID- 15452872
TI  - The Drosophila RNA-binding protein Lark is required for the organization of the
      actin cytoskeleton and Hu-li tai shao localization during oogenesis.
AB  - Elimination of maternal expression of the Drosophila RNA-binding protein Lark
      results in female sterility. Here we show that this is due to a requirement
      during oogenesis. Developing oocytes from lark(1) germline clones (GLCs) are
      often smaller than normal due to defects in nurse cell cytoplasmic "dumping."
      Late-stage egg chambers from lark(1) GLCs contain low levels of cortical and ring
      canal associated actin and completely lack nurse cell cytoplasmic F-actin
      bundles, suggesting the "dumping" phenotype is due to a defect in the actin
      cytoskeleton. Localization of Hu-li tai shao (Hts) protein, a component of ring
      canals, is also disrupted in these mutants. In addition to the dumpless
      phenotype, we observed a buildup of late-stage egg chambers, a phenotype that
      correlates with the decrease in egg-laying observed in the mutants. We postulate
      that this phenotype is due to defects in the cytoskeletal integrity of eggs since
      retained and oviposited eggs are fragile and often deflated. These mutant
      phenotypes are likely due to disruption of an RNA-binding function of Lark as
      similar phenotypes were observed in flies carrying specific RNA-binding domain
      mutations. We propose that Lark functions during oogenesis as an RNA-binding
      protein, regulating mRNAs required for nurse cell transport or apoptosis.

PMID- 15452873
TI  - RNAi-mediated inhibition of gene function in the follicle cell layer of the
      Drosophila ovary.
AB  - RNA-mediated interference (RNAi) has been reported to be an effective reverse
      genetic approach for studying gene function in various organisms. To assess RNAi
      as a means of examining genes expressed in ovarian follicle cells for their
      involvement in embryonic dorsal-ventral patterning, we tested the ability of
      transgenically expressed double-stranded RNA (dsRNA) directed against the dorsal
      group gene windbeutel to generate phenotypic effects in the progeny of expressing
      females. We observed that expression in follicle cells under the control of Gal4
      transcribed from the strong and widely expressed alphaTub84B or Actin5C promoters
      led to efficient dorsalization of progeny embryos. Surprisingly, a variety of
      strongly expressed follicle cell-specific Gal4 enhancer trap lines failed to
      elicit an RNAi phenotype in combination with the windbeutel-specific dsRNA. These
      results stress the importance of careful choice of expression system and of
      conditions for use in transgenic RNAi-mediated studies of gene function.

PMID- 15452874
TI  - Generation of novel conditional and hypomorphic alleles of the Smad2 gene.
AB  - Smad2 is an intracellular mediator of the transforming growth factor beta
      signaling (TGFbeta) pathway. It has been previously shown that, in the mouse,
      ablation of functional Smad2 results in embryonic lethality due to gastrulation
      defects. To circumvent the early lethality and study the spatially and temporally
      specific functions of Smad2, we utilized the Cre-loxP system to generate a Smad2
      conditional allele. Here we show that a conditional allele, Smad2(flox), was
      generated. In this allele, exons 9 and 10 are flanked by loxP sites and the gene
      is functionally wildtype. Cre-mediated recombination results in a deletion allele
      which phenocopies our previously reported Smad2(DeltaC) null mutation. To
      generate this conditional allele, we first made a targeted mutation which
      introduced a floxed neo cassette into intron 10. This allele (Smad2(3loxP))
      functions hypomorphically when placed opposite a null allele, and unlike the
      other published Smad2 hypomorphic allele, can be maintained in the homozygous
      state.

PMID- 15452877
TI  - The Journal of Gene Medicine European Society of Gene Therapy Young Investigator
      Award 2004.

PMID- 15452878
TI  - Interferon-alpha and antisense K-ras RNA combination gene therapy against
      pancreatic cancer.
AB  - Interferon alpha (IFN-alpha) is used worldwide for the treatment of a variety of
      cancers. For pancreatic cancer, recent clinical trials using IFN-alpha in
      combination with standard chemotherapeutic drugs showed some antitumor activity
      of the cytokine, but the effect was not significant enough to enlist pancreatic
      cancer as a clinically effective target of IFN-alpha. In general, an improved
      therapeutic effect and safety are expected for cytokine therapy when given in a
      gene therapy context, because the technology would allow increased local
      concentrations of this cytokine in the target sites. In this study, we first
      examined the antiproliferative effect of IFN-alpha gene transduction into
      pancreatic cancer cells. The expression of IFN-alpha effectively induced growth
      suppression and cell death in pancreatic cancer cells, an effect which appeared
      to be more prominent when compared with other types of cancers and normal cells.
      Another strategy we have been developing for pancreatic cancer targets its
      characteristic genetic aberration, K-ras point mutation, and we reported that the
      expression of antisense K-ras RNA significantly suppressed the growth of
      pancreatic cancer cells. When these two gene therapy strategies are combined, the
      expression of antisense K-ras RNA significantly enhanced IFN-alpha-induced cell
      death (1.3- to 3.5-fold), and suppressed subcutaneous growth of pancreatic cancer
      cells in mice. Because the 2',5'-oligoadenylate synthetase/RNase L pathway, which
      is regulated by IFN and induces apoptosis of cells, is activated by double-strand
      RNA, it is plausible that the double-strand RNA formed by antisense and
      endogenous K-ras RNA enhanced the antitumor activity of IFN-alpha. This study
      suggested that the combination of IFN-alpha and antisense K-ras RNA is a
      promising gene therapy strategy against pancreatic cancer.

PMID- 15452879
TI  - Electrotransfer of human IL-1Ra into skeletal muscles reduces the incidence of
      murine collagen-induced arthritis.
AB  - BACKGROUND: It has previously been demonstrated that high levels of gene
      expression in skeletal muscles can be achieved after direct in vivo
      electrotransfer of naked plasmid DNA. The purpose of this study is to examine the
      potential of in vivo electroporation of plasmid DNA encoding human IL-1Ra for the
      prevention of murine collagen-induced arthritis (CIA). METHODS: DBA/1 mice were
      injected in gastrocnemius muscles with plasmid DNA followed by in vivo
      electroporation. To uncover the optimum conditions of gene transfer, various
      electric field strengths and different amounts of plasmid DNA were applied. Calf
      muscles around the injected areas were investigated with histological methods for
      damage to muscle tissue. The levels of human IL-1Ra expression in the injected
      area and also in the serum were determined with ELISA for human IL-1Ra. Based on
      these data, the effects of electrotransfer of plasmid DNA were tested using the
      murine CIA model. DBA/1 mice were immunized with bovine collagen type II at the
      base of the tail. On day 21, mice were given a booster injection with the same
      antigen. Mice were divided into two groups on day 26. One group of mice received
      plasmid containing the IL-1Ra cDNA sequence, while control mice were given
      plasmid lacking the IL-1Ra coding sequence. The incidence of arthritis was
      evaluated by macroscopic analysis, histological analysis, and the levels of
      inflammatory cytokines. RESULTS: IL-1Ra expression increased as a function of the
      electrical field strength and the amount of DNA. 200 V/cm (eight pulses; 20 ms
      per pulse; 1 Hz) and 15 microg of plasmid DNA per mouse were found to be optimum
      for gene transfer. After in vivo electroporation, gene expression in both muscle
      and serum increased gradually, reaching a peak value on day 10. Significant
      levels of human IL-1Ra expression were maintained for 20 days. Macroscopic
      analysis showed that the onset of CIA was significantly inhibited by direct
      electrotransfer of plasmid DNA encoding human IL-1Ra. Histological analysis of
      knee joints showed that the incidence of arthritis in knee joints was also
      prevented. The levels of mouse IL-1beta and IL-12 in paws were significantly
      lower in the group treated with IL-1Ra than those in the control group.
      CONCLUSIONS: These results demonstrate that direct electrotransfer of plasmid
      containing the human IL-1Ra cDNA sequence to skeletal muscle can reduce the
      incidence of CIA in mice.

PMID- 15452880
TI  - The modulatory effects of ellagic acid and vitamin E succinate on TCDD-induced
      oxidative stress in different brain regions of rats after subchronic exposure.
AB  - The effects of ellagic acid (EA) and vitamin E succinate (VES) on 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD)-induced oxidative stress in different brain
      regions of rats have been studied after subchronic exposure to the compounds.
      TCDD was administered to groups of rats at a dose of 46 ng/kg/day for 90 days. EA
      and VES were administered to groups of rats, either separately or simultaneously
      with TCDD, every other day for 90 days. At the end of the treatment period,
      animals were sacrificed and brains were dissected to cerebral cortex (Cc),
      hippocampus (H), cerebellum (C), and brain stem (Bs), and were assayed for
      production of superoxide anion (SA), lipid peroxidation (LP), and DNA single
      strand breaks (SSBs). While TCDD administration to rats resulted in significant
      production of SA, LP, and DNA SSBs in Cc and H, simultaneous administration of
      VES or EA with the xenobiotics resulted in significant protection against those
      effects. The results also indicate that VES provided a better protyection against
      TCDD-induced effects in brains when compared with EA.

PMID- 15452881
TI  - Update on olfactory mucosal metabolic enzymes: age-related changes and N
      acetyltransferase activities.
AB  - We have expanded previous observations on olfactory metabolic enzymes by
      examining the content of various metabolic enzymes in the olfactory mucosa of the
      male Long-Evans rat at different ages. Age-related changes in metabolic enzyme
      content may be related to changes in susceptibility to toxicants with age and may
      also contribute to altered odorant perception in the elderly. While some enzymes
      did not vary over the age range examined, decreases in the microsomal content of
      other enzymes were observed. While mRNA for acetyltransferase enzymes has
      previously been described in olfactory mucosa, the markedly higher activity of
      olfactory acetyltransferases compared to liver had not previously been described.
      Acetyltransferases are important in the metabolism of drugs and toxicants that
      are aromatic amine derivatives and may contribute to the bioactivation of rodent
      olfactory mucosal carcinogens such as 2,6-dimethylaniline and alachlor. These
      studies show that the olfactory mucosa varies in its metabolic capacity with age,
      and characterize another class of metabolic enzymes in the olfactory mucosa, both
      of which may impact significantly on responses to toxicants and therapeutic
      agents in the nasal cavity.

PMID- 15452882
TI  - Protective effect of caffeic acid phenethyl ester (CAPE) on lipid peroxidation
      and antioxidant enzymes in diabetic rat liver.
AB  - The aim of this study was to examine the effect of caffeic acid phenethyl ester
      (CAPE) on lipid peroxidation (LPO) and the activities of antioxidant enzymes such
      as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH
      Px) in the liver of streptozotocin (STZ)-induced diabetic rats. Twenty-seven rats
      were randomly divided into three groups: group I, control non-diabetic rats (n =
      9); group II, STZ-induced, untreated diabetic rats (n = 8); group III, STZ
      induced, CAPE-treated diabetic rats (n = 10), which were intraperitoneally
      injected with CAPE (10 microM kg(-1) day(-1)) after 3 days followed by STZ
      treatment. The liver was excised after 8 weeks of CAPE treatment, the levels of
      malondialdehyde (MDA) and the activities of SOD, CAT, and GSH-Px in the hepatic
      tissues of all groups were analyzed. In the untreated diabetic rats, MDA markedly
      increased in the hepatic tissue compared with the control rats (p < 0.0001).
      However, MDA levels were reduced to the control level by CAPE. The activities of
      SOD, CAT, and GSH-Px in the untreated diabetic group were higher than that in the
      control group (p < 0.0001). The activities of SOD and GSH-Px in the CAPE-treated
      diabetic group were higher than that in the control group (respectively, p <
      0.0001, p < 0.035). There were no significant differences in the activity of CAT
      between the rats of CAPE-treated diabetic and control groups. Rats in the CAPE
      treated diabetic group had reduced activities of SOD and CAT in comparison with
      the rats of untreated diabetic group (p < 0.0001). There were no significant
      differences in the activity of GSH-Px between the rats of untreated diabetic and
      CAPE-treated groups. It is likely that STZ-induced diabetes caused liver damage.
      In addition, LPO may be one of the molecular mechanisms involved in STZ-induced
      diabetic damage. CAPE can reduce LPO caused by STZ-induced diabetes.

PMID- 15452883
TI  - Lead-induced oxidative stress and hematological alterations and their response to
      combined administration of calcium disodium EDTA with a thiol chelator in rats.
AB  - The therapeutic efficacy of calcium disodium ethylenediaminetetracetic acid
      (CaNa(2)EDTA) and the two thiol chelators, 2,3-dimercaptopropane 1-sulfonate
      (DMPS) and monoisoamyl dimercaptosuccinic acid (MiADMSA) was studied, both
      individually and in combination, in reducing lead concentration in blood and soft
      tissues and in restoring lead induced altered biochemical variables in rats.
      Exposure to subacute dose of lead implicated a critical role of reactive oxygen
      species (ROS) and oxidative stress in altering the normal values of these
      variables. Exposure to lead caused a significant inhibition of blood delta
      aminolevulinic acid dehydratase (ALAD), an important enzyme in the haem synthesis
      pathway and glutathione (GSH) level. These changes were also accompanied by
      inhibition of ALAD activity in kidney, delta-aminolevulinic acid synthase (ALAS)
      activities in liver and changes in platelet counts in whole blood suggesting
      disturbed haem synthesis pathway. Lead exposure also led to a pronounced
      depletion of brain GSH contents, superoxide dismutase (SOD) activity, an increase
      in thiobarbituric acid reactive substances (TBARS), and activity of glutathione S
      transferase (GST). Specific activities of membrane-bound enzymes,
      acetylcholinesterase (AChE) and monoamine oxidase (MAO), were significantly
      inhibited on lead exposure. These biochemical changes were correlated with
      increased uptake of lead in blood and soft tissues. Post lead exposure treatment
      with MiADMSA in particular provided significant recovery in altered biochemical
      variables besides significant depletion of tissue lead burden. Treatment with
      CaNa(2)EDTA and DMPS individually had only moderate beneficial effects on tissue
      oxidative stress, although they were equally effective in the removal of tissue
      lead burden. Tissue zinc and copper levels did not depict any significant
      depletion, although changes like marked depletion of zinc following CaNa(2)EDTA
      and copper after MiADMSA administration were of some concern. Combined
      administration of CaNa(2)EDTA, particularly with MiADMSA, was the most effective
      treatment protocol compared to all other treatments. It can be concluded from our
      present results that combined therapy with CaNa(2)EDTA and MiADMSA proved
      significantly better in restoring biochemical and clinical variables over
      monotherapy with these chelating agents against subacute lead exposure in adult
      rats.

PMID- 15452884
TI  - Molecular cloning, genomic organization and functional characterization of a new
      short-chain potassium channel toxin-like peptide BmTxKS4 from Buthus martensii
      Karsch(BmK).
AB  - Scorpion venom contains many small polypeptide toxins, which can modulate Na(+),
      K(+), Cl(-), and Ca(2+) ion-channel conductance in the cell membrane. A full
      length cDNA sequence encoding a novel type of K(+)-channel toxin (named BmTxKS4)
      was first isolated and identified from a venom gland cDNA library of Buthus
      martensii Karsch (BmK). The encoded precursor contains 78 amino acid residues
      including a putative signal peptide of 21 residues, propeptide of 11 residues,
      and a mature peptide of 43 residues with three disulfide bridges. BmTxKS4 shares
      the identical organization of disulfide bridges with all the other short-chain
      K(+)-channel scorpion toxins. By PCR amplification of the genomic region encoding
      BmTxKS4, it was shown that BmTxKS4 composed of two exons is disrupted by an
      intron of 87 bp inserted between the first and the second codes of Phe (F) in the
      encoding signal peptide region, which is completely identical with that of the
      characterized scorpion K(+)-channel ligands in the size, position, consensus
      junctions, putative branch point, and A+T content. The GST-BmTxKS4 fusion protein
      was successfully expressed in BL21 (DE3) and purified with affinity
      chromatography. About 2.5 mg purified recombinant BmTxKS4 (rBmTxKS4) protein was
      obtained by treating GST-BmTxKS4 with enterokinase and sephadex chromatography
      from 1 L bacterial culture. The electrophysiological activity of 1.0 microM
      rBmTxKS4 was measured and compared by whole cell patch-clamp technique. The
      results indicated that rBmTxKS4 reversibly inhibited the transient outward K(+)
      current (I(to)), delayed inward rectifier K(+) current (I(k1)), and prolonged the
      action potential duration of ventricular myocyte, but it has no effect on the
      action potential amplitude. Taken together, BmTxKS4 is a novel subfamily member
      of short-strain K(+)-channel scorpion toxin.

PMID- 15452885
TI  - A cyclic peptide, L1AD3, induces early signs of apoptosis in human leukemic T
      cell lines.
AB  - L1AD3 is a small cyclic synthetic peptide designed to resemble the first loop of
      a cobra venom cytotoxin. Instead of inducing membrane disruption similar to that
      caused by the parent toxin, L1AD3 promotes extensive and unusually rapid
      apoptosis in leukemic T-cells without making the plasma membrane permeable to
      small fluorescent dyes. Within 4 h, micromolar concentrations of L1AD3 almost
      totally inhibit thymidine incorporation, and ATP levels decrease significantly.
      By contrast, normal human white blood cells are not affected by L1AD3, nor is
      heart cell function affected by it. If L1AD3 kills by interacting with targets
      that are different from those of currently applied agents, this peptide, or a
      derivative of it, could become a useful adjunct for cancer chemotherapy.

PMID- 15452886
TI  - Quantitative analysis of total mitochondrial DNA: competitive polymerase chain
      reaction versus real-time polymerase chain reaction.
AB  - An efficient and effective method for quantification of small amounts of nucleic
      acids contained within a sample specimen would be an important diagnostic tool
      for determining the content of mitochondrial DNA (mtDNA) in situations where the
      depletion thereof may be a contributing factor to the exhibited pathology
      phenotype. This study compares two quantification assays for calculating the
      total mtDNA molecule number per nanogram of total genomic DNA isolated from human
      blood, through the amplification of a 613-bp region on the mtDNA molecule. In one
      case, the mtDNA copy number was calculated by standard competitive polymerase
      chain reaction (PCR) technique that involves co-amplification of target DNA with
      various dilutions of a nonhomologous internal competitor that has the same primer
      binding sites as the target sequence, and subsequent determination of an
      equivalence point of target and competitor concentrations. In the second method,
      the calculation of copy number involved extrapolation from the fluorescence
      versus copy number standard curve generated by real-time PCR using various
      dilutions of the target amplicon sequence. While the mtDNA copy number was
      comparable using the two methods (4.92 +/- 1.01 x 10(4) molecules/ng total
      genomic DNA using competitive PCR vs 4.90 +/- 0.84 x 10(4) molecules/ng total
      genomic DNA using real-time PCR), both inter- and intraexperimental variance were
      significantly lower using the real-time PCR analysis. On the basis of
      reproducibility, assay complexity, and overall efficiency, including the time
      requirement and number of PCR reactions necessary for the analysis of a single
      sample, we recommend the real-time PCR quantification method described here, as
      its versatility and effectiveness will undoubtedly be of great use in various
      kinds of research related to mitochondrial DNA damage- and depletion-associated
      disorders.

PMID- 15452887
TI  - Microarrays in biology and medicine.
AB  - The remarkable speed with which biotechnology has become critical to the practice
      of life sciences owes much to a series of technological revolutions. Microarray
      is the latest invention in this ongoing technological revolution. This technology
      holds the promise to revolutionize the future of biology and medicine unlike any
      other technology that preceded it. Development of microarray technology has
      significantly changed the way questions about diseases and/or biological
      phenomena are addressed. This is because microarrays facilitate monitoring the
      expression of thousands of genes or proteins in a single experiment. This
      enormous power of microarrays has enabled scientists to monitor thousands of
      genes and their products in a given living organism in one experiment, and to
      understand how these genes function in an orchestrated manner. Obtaining such a
      global view of life at the molecular level was impossible using conventional
      molecular biological techniques. However, despite all the progress made in
      developing this technology, microarray is yet to reach a point where all data are
      obtained, analyzed, and shared in a standardized fashion. The present article is
      a brief overview of microarray technologies and their applications with an
      emphasis on DNA microarray.

PMID- 15452888
TI  - Mycobacterium sp., Rhodococcus erythropolis, and Pseudomonas putida behavior in
      the presence of organic solvents.
AB  - This work aimed at studying the behavior and tolerance of Mycobacterium sp. NRRL
      B-3805, Rhodococcus erythropolis DCL14 and Pseudomonas putida S12 cells in the
      presence of various concentrations of water miscible (ethanol, butanol, and
      dimethylformamide, up to 50% v/v) and water immiscible solvents (dodecane, bis(2
      ethylhexyl) phthalate and toluene, up to 5% v/v). When incubated in the presence
      of these solvents, the cells were found to have lower tolerance to butanol and
      toluene than to the remaining solvents. Nevertheless, the concentrations of
      solvents endured by the tested strains show that they are quite solvent-tolerant,
      confirming their potential as biocatalysts in nonconventional systems.
      Microscopic observation of samples showed that the hydrophobic Mycobacterium sp.
      and R. erythropolis cells were able to aggregate to protect the population under
      stress conditions. Comparison of the results obtained at the single cell level by
      fluorescence microscopy and colony development on agar plates indicated that the
      primary effects of most solvents tested were on the cell membrane and replicating
      capability of the cells.

PMID- 15452889
TI  - Wide-range length metrology by dual-imaging-unit atomic force microscope based on
      porous alumina.
AB  - A new dual-imaging-unit atomic force microscope (DIU-AFM) was developed for wide
      range length metrology. In the DIU-AFM, two AFM units were combined, one as a
      reference unit, and the other a test one. Their probes with Z piezo elements and
      tips were horizontally set in parallel at the same height to reduce errors due to
      geometric asymmetry. An XY scanner was attached to an XY block that was able to
      move in the X direction with a step of about 500 nm. A standard porous alumina
      film was employed as the reference sample. Both reference sample and test sample
      were installed at the center of the XY scanner on the same surface and were
      simultaneously imaged. The two images had the same lateral size, and thus the
      length of the test sample image could be accurately measured by counting the
      number of periodic features of the reference one. The XY block together with the
      XY scanner were next moved in the X direction for about 1.5 microm and a second
      pair of reference and test images were obtained by activating the scanner. In
      this way, a series of pairs of images were acquired and could be spliced into two
      wide-range reference and test images, respectively. Again, the two spliced images
      were of the same size and the length of test image was measured based on the
      reference one. This article presents a discussion about the structure and control
      of the DIU-AFM system. Some experiments were carried out on the system to
      demonstrate the method of length calculation and measurement. Experiments show a
      satisfactory result of wide-range length metrology based on the hexagonal
      features of the porous alumina with a periodic length of several tens of
      nanometers. Using this method the DIU-AFM is capable of realizing nanometer-order
      accuracy length metrology when covering a wide range from micron to several
      hundreds of microns, or even up to millimeter order.

PMID- 15452890
TI  - Multidimensional long-term time-lapse microscopy of in vitro peripheral nerve
      regeneration.
AB  - In order to test the effectiveness of a new advanced time-lapse microscopy
      imaging and image processing and analysis system, and to do quantitative and
      qualitative temporal analyses of in vitro peripheral nerve regeneration, long
      term time-lapse imaging of cultures of mouse dorsal root ganglia (DRGs) was
      performed. DRGs were placed in a Petri dish, covered with collagen gel, their
      attached peripheral nerves were cut in the middle, creating a gap, and the dish
      was filled with culture medium. Six preparations were kept on the time-lapse
      imaging system, which provides a suitable incubation environment and enables to
      capture images from multiple coordinates at x,y,z axes at desired time intervals
      for 13 days. In general, the time-lapse imaging system proved quite stable and
      efficient, although some improvements are certainly required. Two main components
      of peripheral nerve regeneration, outgrowth of axons and activities of resident
      cells, were examined. Axons started to grow during the first hour of incubation
      with a 16.5 microm/h rate and showed the slowest rates (0.7 microm/h) on days 8
      and 9, after which they resumed higher speeds again. The first cell came out of
      the proximal end of the cut nerve on the second day and it was a Schwann cell
      (SC), which was the prominent cell type in the preparations throughout the
      experiment. SCs were higher in number (83.15% of all cells) but slower in
      migration (3.4 vs. 7.3 microm/h, P < 0.001) than other cells. Other observed
      characteristics of axonal outgrowth and cellular activity and interactions
      between axons and the cells are discussed.

PMID- 15452891
TI  - Ultrastructural and immunocytochemical analyses of opioid treatment effects on
      PC3 prostatic cancer cells.
AB  - Some opioid peptides are able to inhibit the growth of human prostatic cancer
      cells; in particular, the [D-Ala(2),D-Leu(5)] enkephalin (DADLE) reduces PC3 cell
      growth. In order to understand how DADLE decreases cell proliferation, we
      investigated, by electron microscopy, its effects on PC3 cellular components. PC3
      cells were incubated with DADLE and processed for both ultrastructural morphology
      and immunoelectron microscopy. Some cells were incubated with BrU to determine
      the transcriptional rate. BrU and DADLE molecules were detected by immunogold
      techniques and the labeling was quantitatively evaluated. Modifications of some
      cytoplasmic and nuclear components were observed in DADLE-treated cells.
      Moreover, treated cells incorporated lower amounts of BrU than control cells.
      DADLE molecules were located in the cytoplasm and in the nucleus, especially on
      mRNA transcription and early splicing sites. Our data suggest that DADLE is able
      to slow down the synthetic activity of PC3 cells, perhaps interfering with
      nuclear functions.

PMID- 15452892
TI  - Improvement of microanatomical research by combining corrosion casts with MicroCT
      and 3D reconstruction, exemplified in the circulatory organs of the woodlouse.
AB  - A SkyScan-1072 high-resolution desktop microtomograph was used to visualize the
      3D morphology of the circulatory system of Porcellio scaber (Crustacea,
      Malacostraca, Isopoda) at the micrometer level. Prior to MicroCT investigation,
      the circulatory system was injected with a fast-hardening resin, permitting a
      better contrast of the vascular structures that are normally hollow after
      fixation. Stacks of tomographic images were used to reconstruct the circulatory
      system three-dimensionally. The spatial resolution achieved by the microtomograph
      is about 3.5 microm. The technique provides detailed tomographic images of the
      inner organs and makes precise 3D reconstructions of the circulatory system in
      arthropods possible. The results were compared with conventional histological
      data. MicroCT permits a high number of specimens to be screened in a short time,
      which is essential for the improvement of modern morphological research in a
      cladistic framework. Histological techniques, however, are still essential for
      gathering information at the cellular level.

PMID- 15452893
TI  - The switch mechanism of the cell death mode from apoptosis to necrosis in
      menadione-treated human osteosarcoma cell line 143B cells.
AB  - Time-dependent changes in the cell death mode from apoptosis to necrosis were
      studied in cultured 143B cells treated with menadione, an anti-cancerous drug,
      excluding a possible involvement of "secondary necrosis." The population of
      apoptotic cells judged by FITC-Annexin V and propidium iodide (PI) double
      staining reached its maximum at 6 hours after 100 microM menadione treatment
      followed by an abrupt decrease thereafter, while that of necrotic cells
      continuously increased reaching 90% at 24 hours. Electron microscopically, cells
      attached to the culture dish at 6 hours after the treatment consisted of two
      different types of cells: cells with typical apoptotic features occupying the
      major population and those with condensed nuclei and swollen cytoplasm. Cells
      attached to the culture dish at 8 hours after the treatment consisted exclusively
      of those with condensed nuclei and swollen cytoplasm. Mitochondria in these cells
      showed various structural changes: those swollen to various degrees with
      deposition of flocculent densities, or those with highly condensed matrix.
      Distinct decreases both in intracellular levels of ATP and caspase-3-like
      activities and remarkable elevations of intracellular levels of superoxide, which
      were partly suppressed by NAD(P)H oxidase inhibitors, occurred at 6 hours after
      the treatment. These results may suggest that distinct increases of the
      intracellular level of superoxide derived from plasma membrane NAD(P)H oxidase
      besides that from mitochondria have triggered the transition of cell death mode
      from apoptosis to necrosis. Transition of highly condensed mitochondria to
      extremely swollen ones may reflect necrotic processes in menadione-treated cells.
      The present study strongly suggests that time-dependent study is essential using
      the electron microscopic technique to analyze detailed processes in the changes
      of the cell death mode.

PMID- 15452894
TI  - A new role for chondrocytes as non-professional phagocytes. An in vitro study.
AB  - Chondrocytes are capable of engulfing latex particles, cell detritus, and
      necrotic and apoptotic remains in vitro. It is conceivable that chondrocytes
      might be involved in the clearance by phagocytosis of different materials within
      the cartilage. In fact, so far there is no evidence for the presence of
      "professional phagocytes" (macrophages and neutrophils) in this tissue.
      Chondrocyte suspensions obtained from rat knees and hips were cultured to assess
      phagocytosis of latex particles (1 microm), articular cartilage detritus, and
      necrotic and apoptotic chondrocyte remains (induced by VP-16 1 mM). We observed
      that chondrocytes phagocytosed latex particles as evaluated by confocal
      microscopy and flow cytometry. In addition, we observed that chondrocytes
      phagocytosed articular cartilage detritus and necrotic and apoptotic VP-16
      induced-chondrocytes, as observed by bright field microscopy and transmission
      electron microscopy.

PMID- 15452895
TI  - Expression of VEGFR-3 and 5'-nase in regenerating lymphatic vessels of the
      cutaneous wound healing.
AB  - The vascular endothelial growth factor-C (VEGF-C), a specific lymphangiogenic
      growth factor, raises new questions and perspectives in studying lymphatic
      development and regeneration. Wound healing skins in mice were processed for 5'
      nucleotidase (5'-Nase) and VEGFR-3 (the receptor of VEGF-C) histochemical
      staining to distinguish lymphatics from blood capillaries and to analyze
      lymphangiogenesis. In the wounds of 3-5 days after injury, anti-VEGFR-3
      immunopositive signals unevenly appeared in 5'-Nase-positive lymphatic vessels in
      the subcutaneous tissue. A few small circular and irregular lymphatic-like
      structures with VEGFR-3 expression scattered in the dermal and subcutaneous
      tissues. Between days 7 and 15 of the wounds, numerous accumulated vasculatures
      were stained for 5'-Nase and PECAM-1, extending irregularly along the wound edge.
      Von Willebrand factor was expressed in the endothelial cells of blood vessels and
      lymphatics in the subcutaneous tissue. Ultrastructural changes of lymphatic
      vessels developed at different stages, from lymphatic-like structures to newly
      formed lymphatic vessels with an extremely thin and indented wall. Endothelial
      cells of the lymphatic vessel were eventually featured by typical intercellular
      junctions, which deposited with reaction products of VEGFR-3 and 5'-Nase-cerium
      but lacked VEGF-C expression. The present findings indicate that VEGF-C-induced
      lymphangiogenesis occurs from the subcutaneous to the dermis along the wound
      healing edge, especially in the dermal-subcutaneous transitional area, favorable
      to growth of regenerating lymphatic vessels.

PMID- 15452896
TI  - Anticipating loss and other temporal stressors predict traumatic stress symptoms
      among partners of metastatic/recurrent breast cancer patients.
AB  - This study examined pre- and post-loss levels of posttraumatic stress symptoms
      (intrusion and avoidance) in partners of metastatic/recurrent breast cancer
      patients, and the relationship of these symptoms to past, current, and
      anticipatory stressors. The results indicate that 34% (17/50) of the partners
      experienced clinically significant symptom levels prior to the patients' deaths.
      Prior to loss, partners' symptoms were positively associated with their current
      level of perceived stress and anticipated impact of the loss; whereas following
      loss, partners' symptoms were predicted by higher pre-loss levels of symptoms,
      past family deaths, and anticipated impact of the loss. Limitations and treatment
      implications of the present research and directions for future research are
      discussed.

PMID- 15452897
TI  - Malignant effusions: from diagnosis to biology.
AB  - Serous effusions are a frequently encountered clinical manifestation of
      metastatic disease, with breast, ovarian, and lung carcinomas and malignant
      mesothelioma (MM) leading the list. Recently, extensive research has resulted in
      expansion of the antibody panel that is available for effusion diagnosis, thereby
      reducing the risk for error. Despite this progress, relatively little has been
      done in way of understanding the biology of cancer cells in effusions, especially
      those of nonovarian origin. The diagnosis of a malignant effusion signifies
      disease progression and is associated with a worse prognosis regardless of the
      tumor site of origin. However, survival is much more variable with ovarian cancer
      compared with other tumors. Furthermore, cancer cells of different origins differ
      considerably in their biology and have unique phenotypic and genotypic
      characteristics. This review summarizes the current knowledge in this field and
      presents a model for the study of tumor metastasis and disease progression,
      through large comparative studies of malignant cells in effusions, primary
      tumors, and solid metastases. The case also is made for potential applications of
      this rapidly evolving body of knowledge in the diagnosis, classification, and
      prediction of biological behavior of processes resulting in cryptic effusions at
      the clinical level.

PMID- 15452898
TI  - Immunocytochemical staining of p16INK4a protein from conventional Pap test and
      its association with human papillomavirus infection.
AB  - The p16INK4a protein is immunocytochemically detected in liquid-based (LB)
      specimens as a diagnostic marker of cervical dysplasia and neoplasia. Its up
      regulation is promoted by high-risk human papillomavirus (HR-HPV) infection. We
      aimed to detect p16INK4a on conventional Papanicolaou (Pap) test (CPT) slides and
      to determine the relationship between its overexpression and HR-HPV infection.
      CPT and LB Pap test (LBPT) slides (165 samples of each) were examined by
      immunocytochemical staining for p16INK4a. After polymerase chain reaction (PCR),
      HPV-DNA was genotyped by dot blot hybridization. The CPT slides displayed more
      numerous dispersed squamous cells and LBPT slides had a clearer background.
      Positive p16INK4a on CPT occurred in 0% (0/30), 52.5% (21/40), 54.3% (19/35),
      100% (30/30), and 100% (30/30) in normal, atypical squamous cells of undetermined
      significance (ASCUS), low-grade squamous intraepithelial lesions (LSILs), high
      grade SILs (HSILs), and squamous cell carcinomas (SCCs) cases, respectively. LBPT
      slides showed comparable results but were less sensitive. HPV-DNA was detected in
      86.7, 70, 45, 57.14, and 10% in SCCs, HSILs, ASCUS, LSILs, and normal cervical
      cells, respectively. Because HR-HPV was identified in all HPV+ samples of high
      grade dysplasia (HSILs and SCCs) and all positive p16INK4a samples infected with
      HR-HPV, the association of p16INK4a overexpression with HR-HPV infection was
      confirmed. This study suggests that immunocytochemical staining of p16INK4a on
      CPT slides is convenient and cost-effective for cervical cancer screening by the
      detection of dysplastic cells infected with HR-HPV.

PMID- 15452899
TI  - Simultaneous medullary carcinoma of the thyroid gland and Hodgkin's lymphoma in
      bilateral lymph nodes of the neck: a potential pitfall in fine-needle aspiration
      cytology.
AB  - The clinicopathological features and the cytological findings of Hodgkin's
      lymphoma (HL) and medullary carcinoma (MC) of the thyroid gland are described
      appearing simultaneously in different organs of the cervical region of the same
      patient. Although the cytological features of both entities are well known, the
      rare clinical presentation and the epithelium-like Hodgkin and Reed-Sternberg
      (HRS) cells of the syncytial variant of HL led to an erroneous cytological
      diagnosis of metastatic carcinoma of the upper aerodigestive tract.

PMID- 15452901
TI  - Oncocytic parathyroid adenoma: problem in cytological diagnosis.
AB  - Parathyroid lesions, which may occur within the thyroid, may clinically simulate
      thyroid nodules. Fine-needle aspiration (FNA) of these presumably "thyroid
      nodules" can lead to misinterpretation of cytomorphological findings because of
      similarities in cytological features of neoplastic and nonneoplastic parathyroid
      and thyroid lesions. This might be true especially for oncocytic parathyroid
      adenomas and parathyroid adenomas with prominent oncocytic component that,
      although rare, tend to be large and often are associated with minimal
      hyperparathyroidism. We report two cases of this type of clinically "silent"
      parathyroid adenomas that on FNA were diagnosed as Hurthle cell thyroid neoplasm.

PMID- 15452900
TI  - A morphologic and statistical comparative study of small-cell carcinoma and non
      Hodgkin's lymphoma in fine-needle aspiration biopsy material from lymph nodes.
AB  - Small-cell carcinoma (SmC) and high-grade non-Hodgkin's lymphoma (NHL) are
      aggressive neoplasms that require prompt diagnosis and treatment. An immediate
      diagnosis can be obtained using fine-needle aspiration biopsy (FNAB) material
      from lymph nodes (LNs), which are clinically or radiologically suspicious for
      tumor involvement. However, in aspirates from LNs, the cytologic distinction of
      SmC from NHL can be challenging. The purpose of this study was to evaluate the
      usefulness of various cytologic features that can be used during a rapid on-site
      evaluation to differentiate these two entities. Twenty-seven metastatic SmC and
      50 NHLs cases diagnosed by FNAB of LNs were reviewed. All NHL diagnoses (neck,
      29; abdomen, 9; axilla, 6; groin, 5; and parotid, 1) were confirmed with tissue
      sections, flow cytometry, or immunohistochemistry. These cases were classified as
      follicular, 21 (42%); diffuse large B cell, 13 (26%); small lymphocytic, 7 (14%);
      mantle cell, 4 (8%); anaplastic large cell, 2 (4%); and 1 each (2%), Burkitt,
      lymphoplasmacytic, and peripheral T-cell lymphomas. Immunochemistry confirmed the
      cytologic diagnoses of all SmC cases (neck, 16; mediastinum, 9; abdomen, 1; and
      axilla, 1) with either positive chromogranin or synaptophysin. All specimens were
      reviewed independently by three cytopathologists who were unaware of the original
      diagnoses. The presence and proportion of single (noncohesive) tumor cells,
      lymphoglandular bodies, nuclear fragments, paranuclear blue inclusions, nuclear
      molding, evenly dispersed fine-granular chromatin, crush artifact, and
      composition of cell clusters (monomorphic vs. polymorphic) were statistically
      evaluated. The presence of evenly dispersed fine-granular chromatin, paranuclear
      blue inclusions, and nuclear fragments was each statistically significant in
      differentiating SmC when compared with NHL (P < 0.01). The remaining features
      were not significant in distinguishing SmC from NHL in LN aspirates. The
      identification of distinct cytologic findings such as evenly dispersed fine
      granular chromatin, paranuclear blue inclusions, and nuclear fragments can be a
      valuable aid to accurately diagnose and differentiate metastatic SmC from NHL in
      FNAB preparations from LNs.

PMID- 15452902
TI  - Primary intraosseous (central) salivary gland neoplasms in jaw bones: report of a
      mucoepidermoid carcinoma of the mandible diagnosed by fine-needle aspiration
      cytology.
AB  - A case of intraosseous (central) mucoepidermoid carcinoma of the mandible
      diagnosed by fine-needle aspiration (FNA) cytology, with the diagnosis confirmed
      by surgical resection of the tumor is presented. Mucoepidermoid carcinoma is the
      most common histotype of malignant and benign salivary gland tumors, which
      occasionally arise within the facial bones of mandible and maxilla, besides their
      ordinary derivation from the major and minor salivary glands of the head and neck
      regions. This case is unusual in that although tumors of the jaws abound, only
      rare reports of intraosseous salivary gland-type lesions sampled by FNA exist.
      The current concepts exploring the intraosseous derivation of salivary gland
      tumors are presented and certain points on FNA technic for adequate sampling of
      such lesions are related.

PMID- 15452903
TI  - Inflammatory pseudotumor: a diagnostic dilemma in cytopathology.
AB  - Inflammatory pseudotumor (IPT) is a rare space-occupying lesion of unknown
      etiology that can mimic malignancy on clinicoradiological and pathological
      examination. A review of the cytopathology archives at The Johns Hopkins Hospital
      identified 12 cases from eight patients with histologically proven IPT (lung,
      seven patients; liver, five patients). There were six men and two women with an
      age range of 28-84 yr (mean age, 59 yr). Presenting complaints of IPT of the lung
      included shortness of breath and hemoptysis, and in cases of IPT of the liver
      complaints included abdominal pain and elevated liver function tests (LFTs). All
      cases were found to have mass lesions suspicious for a neoplasm on radiographic
      examination. Cytological specimens consisted of fine-needle aspiration (FNA;
      seven specimens) and bronchial brush/wash (five specimens). Diagnostic accuracy
      of cytology for IPT was low (5/12, 42%). IPT showed hypercellular smears (on FNA)
      with an admixture of various cell types including inflammatory cells with
      predominance of plasma cells, fibroblastic proliferation, granulation tissue
      formation, and atypical-appearing histiocytes with enlarged nuclei and
      intranuclear inclusions. Fibroblastic proliferation with mitoses may mimic
      mesenchymal neoplasms. Cytomorphology is nonspecific and IPT usually is a
      diagnosis of exclusion.

PMID- 15452904
TI  - Cytological diagnosis of cystic brain tumors: a retrospective study of 88 cases.
AB  - The stereotaxic aspiration of cystic brain tumors is performed to provide cyst
      decompression and/or to facilitate surgical resection. The purpose of our study
      was to determine the diagnostic value of brain cyst fluid cytology, especially in
      clinically suspected recurrent tumors with no histological follow-up (HF), when a
      diagnosis is most needed. We reviewed the cytological diagnoses of 88 aspirates
      from 70 patients with cystic brain tumors between 1995 and 2001, of which 31 had
      a prior known malignancy including 18 primary brain tumors (PBTs) and 13
      adenocarcinomas (ACAs). Sixty-nine of 88 aspirates were obtained
      intraoperatively. Nineteen of 88 aspirates were obtained from 10 patients with
      recurrent or persistent cystic brain tumors (8 patients with PBT and 2 patients
      with ACA), with available clinicoradiological correlation (magnetic resonance
      imaging/computed tomography [MRI/CT] scans) in 13 of them. The 88 aspirates were
      classified in three categories: 28 positive (32%), 15 atypical (17%), and 45
      negative (51%). Eight of 28 positive cases (5 case of PBT, 2 cases of ACA, and 1
      case of melanoma) were given a nonspecific diagnosis of malignant neoplasm (9% of
      all cases). Fifteen of 28 positive cases (6 cases of PBT, 8 cases of ACA, and 1
      case of melanoma) were diagnosed correctly and confirmed by HF (17% of all
      cases). Four of 28 cases were ACA diagnosed solely by cytology (<4% of all
      cases). One neurocytoma (1/28) case was mistaken for an oligodendroglioma despite
      cell blocks (CBs) and immunophenotyping (IPT) (<1% of all cases). Eleven of 15
      atypical cases were 8 cases of PBT, 2 cases of ACA, and 1 case of postoperative
      change (PC). Four of 15 atypical cases (from three patients with suspected PBT
      recurrence) could not be further characterized by CB/IPT and had no HF. Twenty
      seven of 45 negative cases were falsely negative (23 cases of PBT, 3 cases of
      ACA, and 1 case of malignant neoplasm); 11/45 cases were PC, and 7/45 (from five
      patients with clinically suspected tumor recurrence) cases had no HF. Cytological
      evaluation of brain cyst fluid is not a reliable means of diagnosing cystic brain
      neoplasms (including recurrences) due to a high false negative rate and a low
      sensitivity. Most of the negative or atypical cases (68% of all cases) were
      recurrent PBT of glial origin that may not be prone to exfoliate. These
      cytological specimens consisted of lysed blood, obscuring inflammatory cells, and
      degenerated diagnostic cells if any, yielding inconclusive results.

PMID- 15452905
TI  - Hepatic angiomyolipoma: report of two cases with emphasis on smear cytomorphology
      and the use of cell block with immunohistochemical stains.
AB  - Angiomyolipoma is a benign mesenchymal lesion that occurs most commonly in the
      kidney. Its occurrence in the liver is relatively rare. We report two cases of
      hepatic angiomyolipoma diagnosed by ultrasound-guided, needle aspiration biopsy.
      One of the patients was a previously healthy 62-yr-old woman who presented with a
      hepatic mass incidentally during a healthy examination. The other patient was a
      67-yr-old man, a victim of chronic hepatitis C, who was found to have a hepatic
      tumor in the right lobe during regular follow-up. Cytologic preparations of the
      two hepatic masses showed some mature adipocytes admixed with clusters of
      variable-sized mesenchyme-like cells with fibrillar cytoplasm and indistinct
      cytoplasmic borders. Some of the cells were round to oval and others were spindle
      shaped with oval, cigar-shaped or elongated nuclei. The nuclear chromatin was
      fine and some cells showed round nucleoli. No thick-walled blood vessels were
      noted in the cytological smears. In the cell block preparations, a mixture of
      thick-walled blood vessels, mature adipose tissue, and bundles of variable-sized
      smooth muscle cells were noted. The spindle or epithelioid smooth muscle cells
      were positive for vimentin, alpha-smooth muscle actin, and human melanoma black
      (HMB)-45 but negative for desmin and S100 protein in immunohistochemical stains.
      The purpose of the current study is to describe cytological features of this
      lesion with differential diagnosis because pathologists may be called on to
      render a diagnosis on needle aspiration. HMB-45 has been proved to be a sensitive
      marker for the smooth muscle component of angiomyolipoma. Cell block preparations
      assisted with immunohistochemical staining should be emphasized for definite
      diagnosis. Although a surgical procedure may still be necessary once a diagnosis
      of angiomyolipoma is made, treatment may be tailored for a less aggressive
      procedure than for malignant hepatic nodules.

PMID- 15452906
TI  - Particle disease: cytopathologic findings of an unusual case.
AB  - Particle disease is a rare lesion that results from an inflammatory response due
      to wear debris-induced osteolysis following arthroplasty. Particles resulting
      from the wear debris cause macrophage activation and phagocytosis. Particle
      disease often leads to joint loosening and implant failure. Radiologically, it
      often results in a well-defined osteolytic lesion-mimicking tumor. A 68-year-old
      man who presented with chronic hip pain following total hip replacement was
      studied by fine-needle aspiration. An ultrasound-guided aspiration revealed
      hypercellular smears consisting predominantly of proliferating mesenchymal cells,
      foamy macrophages, inflammatory cells, and background acellular debris. Numerous
      multinucleated giant cells were observed as well. Differential diagnosis includes
      primary or metastatic clear-cell tumors.

PMID- 15452907
TI  - Metastases in the pancreas from nonhematologic neoplasms: report of 20 cases
      evaluated by fine-needle aspiration.
AB  - We reviewed fine-needle aspiration (FNA) samples of metastatic tumor in the
      pancreas from nonhematologic neoplasms over a 5-year period. In 1,050 total
      procedures, 20 metastases were diagnosed: 9 renal-cell carcinomas (RCCs), 3
      melanomas, 2 pulmonary small-cell carcinomas, 2 breast carcinomas, 1 prostate
      carcinoma, 1 colon adenocarcinoma, 1 pulmonary squamous-cell carcinoma, and 1
      gastrointestinal stromal tumor. A wide range of latency from primary diagnosis
      was noted; the longest was RCC at 12.6 years (range, 5-28). Sites of involvement
      were: 13 heads, 4 bodies, and 3 tails. Eighteen cases presented as a solitary
      mass. The average size was 4.7 cm (range, 1.5-9.8), and a case of RCC (9.8 cm)
      was the largest. In seven cases, the clinical and radiographic impression was of
      a pancreatic primary. We conclude that metastases to the pancreas are rarely
      diagnosed by FNA and may clinically mimic a pancreatic primary.

PMID- 15452908
TI  - Cytological criteria for the diagnosis of intraductal hyperplasia, ductal
      carcinoma in situ, and invasive carcinoma of the breast.
AB  - The advent of mammography screening presents a diagnostic challenge to the
      cytopathologist as an increasing proportion of breast lesions requiring
      investigation will be nonpalpable and up to 40% will be accounted for by atypical
      intraductal hyperplasia and ductal carcinoma in situ, as opposed to previously,
      when these lesions represented less than 10% of palpable tumors. We studied 133
      fine-needle aspirates from breast tumors and found that nuclear morphology,
      myoepithelial cells, signs of invasion, and degree of cellular dissociation are
      among the most potent factors discriminating between benign epithelial
      proliferations, atypical intraductal hyperplasia, ductal carcinoma in situ, and
      invasive carcinoma.

PMID- 15452909
TI  - Fine-needle aspiration cytology in tuberculous lymphadenitis of patients with and
      without HIV infection.
AB  - A study of the cytologic features and role of fine-needle aspiration cytology
      (FNAC) in tuberculous lymphadenitis (TBL) of 21 patients with HIV (group 1) and
      21 patients without HIV (group 2) infection was undertaken. Four cytologic
      patterns were observed, of which necrotizing lymphadenitis (42.9%) and
      necrotizing suppurative lymphadenitis (28.6%) were predominant in group 1 while
      necrotizing granulomatous lymphadenitis (47.7%) and granulomatous lymphadenitis
      (23.8%) were more common in group 2. No pattern was found specific for either
      group. Zeihl-Neelsen-stained cytology smears of group 1 showed a much higher
      percentage of positively (61.9%) and a higher density of acid-fast bacilli than
      group 2. Definitive diagnoses of TBL on FNAC could be provided in 61.9% of group
      1 as against 9.5% of group 2. The need for culture or biopsy for definitive
      diagnosis was higher in group 2. In suspected TBL, diagnostic efficacy can be
      improved and the need for surgical biopsy reduced if material collected on FNA is
      also used for culture.

PMID- 15452911
TI  - Nutritional status of malignant cells and their morphometry.

PMID- 15452910
TI  - Leiomyosarcoma of the urinary bladder: a diagnostic challenge in urine cytology.
AB  - Most of the available data in the literature describe the cytomorphological
      features of exfoliated malignant epithelial cells in urine. There are no
      established diagnostic features that characterize the morphology of exfoliated
      malignant mesenchymal tumor in urine. Here we highlight the problems in the
      diagnosis of these groups of tumors. The presence of discohesive atypical cells
      which lack features of an epithelial nature should make one suspicious of this
      group of tumors.

PMID- 15452912
TI  - Endoscopic ultrasound guided fine-needle aspiration diagnosis of Hodgkin's
      disease in an unusual location.

PMID- 15452913
TI  - Surveys: a tool to provoke thought and identify areas of need.

PMID- 15452914
TI  - Transfusion management strategies: a survey of practicing pediatric
      hematology/oncology specialists.
AB  - BACKGROUND: Little is known about the criteria used by pediatric oncologists for
      the transfusion of red blood cells and platelets to pediatric oncology patients.
      PROCEDURE: Data regarding red blood cell and platelet transfusion practices were
      collected with an internet-based survey of physician members of the American
      Society for Pediatric Hematology/Oncology (ASPH/O). Respondents were asked to
      define platelet and red blood cell transfusion thresholds in a variety of
      clinical scenarios, and to describe criteria for dealing with cytomegalovirus
      (CMV) transmission from blood products, platelet dosing strategies, and
      prevention of RhD alloimmunization. RESULTS: The overall response rate was 31.4%
      (264 of 841). Of the respondents, 76% indicated that their institution had
      defined criteria for acceptable transfusion practice; of these respondents, 114
      (57%) indicated that there were special guidelines for pediatric oncology
      patients. Examination of the distribution of threshold platelet counts and
      hemoglobin levels that would prompt transfusion indicated a wide range of
      transfusion practice in commonly encountered clinical scenarios. Similar
      variability in practice was evident in platelet dosing strategies, CMV prevention
      strategies, and in the use of anti-D in RhD-negative patients who received RhD
      positive platelets. CONCLUSIONS: This current survey demonstrates that
      transfusion practices vary widely among pediatric hematology/oncology specialists
      and that prospective clinical trials may be necessary to determine optimal
      criteria for blood product support in pediatric oncology patients.

PMID- 15452915
TI  - Intramedullary spinal cord astrocytomas in children.

PMID- 15452916
TI  - How did the horned lizard get its horns?

PMID- 15452917
TI  - How did the horned lizard get its horns?

PMID- 15452918
TI  - World Allergy Organization guidelines for prevention of allergy and allergic
      asthma.

PMID- 15452919
TI  - Additive genetic relationships between heifer pregnancy and scrotal circumference
      in Nellore cattle.
AB  - To estimate heritability (h2) for yearling heifer pregnancy and to estimate the
      genetic correlation between heifer pregnancy and scrotal circumference, 18,145
      records of Nellore heifers exposed to breeding at an age of approximately 14 mo
      and 25,466 records of contemporary young bulls were analyzed. Heifer pregnancy
      was considered as a categorical trait, with the value 1 (success) assigned to
      heifers that were pregnant after rectal palpation approximately 60 d after the
      end of a 90-d breeding season and the value 0 (failure) otherwise. A single-trait
      animal model for heifer pregnancy and a two-trait animal model including heifer
      pregnancy and scrotal circumference were used. Contemporary groups were defined
      in two ways: including (CG2) or not including (CG1) weaning management of the
      heifer. Heritability estimates obtained by Method R in single-trait analyses were
      0.68 +/- 0.09 and 0.61 +/- 0.10 using CG1 and CG2 definitions, respectively.
      Heritability estimates for two-trait analyses were 0.69 +/- 0.09 (CG1) and 0.63
      +/- 0.08 (CG2) for heifer pregnancy and 0.57 +/- 0.03 (both CG) for scrotal
      circumference. The genetic correlation estimates between the two traits were 0.20
      +/- 0.12 (CG1) and 0.20 +/- 0.13 (CG2). Based on the results of this study, EPD
      for heifer pregnancy can be used to select bulls for the production of precocious
      daughters and will be more effective than selecting on scrotal circumference EPD
      in Nellore cattle. However, scrotal circumference can be incorporated in a two
      trait analysis to increase the accuracy of prediction for heifer pregnancy EPD
      for young bulls. Using contemporary group without heifer weaning management gave
      higher h2 and, for two-trait analysis, converged more quickly.

PMID- 15452920
TI  - Effect of supplemental vitamin D3 concentration on concentrations of calcium,
      phosphorus, and magnesium relative to protein in subcellular components of the
      longissimus and the distribution of calcium within longissimus muscle of beef
      steers.
AB  - The effect of supplementing diets with various levels of vitamin D3 to provide 0,
      0.5, 1, and 5 million IU/(steer x d) for 8 d before slaughter on the mineral
      content and localization of Ca in LM and muscle fragments was studied during the
      postmortem aging process. Twelve feedlot steers of three biological types were
      given access to the four levels of vitamin D for 8 d before slaughter.
      Differential centrifugation techniques were used to determine the concentrations
      of minerals relative to protein in different muscle fragments on d 3 and 21
      postmortem. Electron microscopy visualization of bound Ca indicated that vitamin
      D3 mobilized Ca from the sarcoplasmic reticulum and transverse tubule system into
      the myofibrils. Bound Ca was concentrated near the Z-line at the A-band/I-band
      juncture within the sarcomere. Supplementing steers with 1 and 5 million
      IU/(steer x d) of vitamin D3 increased (P < 0.05) Ca, P, and Mg concentrations
      per unit of protein in the cytosol. Soluble cytosolic Ca concentrations were
      greater (P < 0.05) on d 21 than on d 3 postmortem only when steers were
      supplemented with 5 million IU/d. Concentrations of Ca, P, and Mg in isolated
      tissues were increased (P < 0.05) in nuclei and myofibrilar proteins by
      supplementing steers with 1 and 5 million IU/ (steer x d) of vitamin D3. All
      supplemental vitamin D3 treatments also increased (P < 0.001) Mg concentrations
      in the cytosol, regardless of aging treatment, and increased Mg concentrations (P
      < 0.04) within the mitochondria at d 3 postmortem. Thus, supplementation of
      feedlot steers with vitamin D3 at levels of 0.5 to 5 million IU/(steer x d)
      increased Ca concentrations within respiring muscle, resulting in increased bound
      tissue Ca concentrations. When the respiring muscle was converted to meat, the
      increased bound tissue Ca resulting from vitamin D3 treatment released Ca
      concentrations into the cytosol during aging (P < 0.05). Results of this study
      indicate that vitamin D3 supplementation increased total cytosolic Ca, P, and Mg
      concentrations in meat.

PMID- 15452921
TI  - Effect of adenine arabinoside on severe Herpesvirus hominis infections in man.
      1973.

PMID- 15452922
TI  - [Treatment concepts for glioma are always case-to-case decisions. Individuality
      determines success].

PMID- 15452923
TI  - An authoritative teaching.

PMID- 15452924
TI  - The PVS is not necessarily fatal.

PMID- 15452925
TI  - On a careful case-by-case basis.

PMID- 15452926
TI  - President's Council on Bioethics: reproduction and responsibility.

PMID- 15452927
TI  - Initial reactions to the Pope's March 20, 2004 allocution.

PMID- 15452928
TI  - Mercy and autonomy: the failure of Battin's justification for euthanasia.

PMID- 15452929
TI  - Irrationality of the irrationality argument against suicide.

PMID- 15452930
TI  - Utilitarian pessimism, human dignity, and the vegetative state: a practical
      analysis of the papal allocution.

PMID- 15452931
TI  - Pope John Paul II on nutrition and hydration: a change of Catholic teaching?

PMID- 15452932
TI  - Non-heart-beating organ donation and Catholic ethics.

PMID- 15452933
TI  - Terri Schiavo and the Catholic connection.

PMID- 15452934
TI  - On life-sustaining treatments and the vegetative state: scientific advances and
      ethical dilemmas.

PMID- 15452935
TI  - Considerations on the scientific and ethical problems related to the vegetative
      state.

PMID- 15452936
TI  - Access to emergency contraception.

PMID- 15452937
TI  - The weight of chronic pelvic pain.

PMID- 15452938
TI  - Motivation, attitudes and experience of donation: a follow-up of women donating
      eggs in assisted conception treatment.
AB  - This paper reports a follow-up of 39 women who had donated eggs to an assisted
      conception unit. Their experience of donation and their motivation and attitudes
      were assessed. Comparisons were made with a group of semen donors who were
      attending a second unit. Female and male donors donated for altruistic reasons
      and neither group wished to have contact with recipients or donor offspring or
      have their identity revealed. Female donors were more involved in the donation
      process and more interested in the outcome of donation. They also appeared to be
      more motivated by 'helping' than male donors. The sample of female donors
      contained a small group of women who were donating to sisters and friends. In
      comparison with anonymous donors, these women reported more effects upon the
      family and issues of secrecy and openness were more apparent. The results are
      discussed in the light of previous studies and the legal framework for donation
      in the UK. Attention is drawn to the lack of social psychological analyses in
      this controversial medical area.

PMID- 15452939
TI  - Abstracts of the American College of Rheumatology 68th annual meeting and the
      Association of Rheumatology Health Professionals 39th annual meeting. October 16
      21, 2004, San Antonio, Texas, USA.

PMID- 15452940
TI  - Abstracts from the 8th Annual Scientific Meeting of the Heart Failure Society of
      America. September 12-15, 2004.

PMID- 15452941
TI  - Abstracts of the 1st Joint ISPD/EuroPD Congress on Peritoneal Dialysis.
      Amsterdam, The Netherlands, August 28-31, 2004.

PMID- 15452942
TI  - Study suggests statins for diabetics with healthy LDL cholesterol levels.

PMID- 15452943
TI  - Five diseases drive much of U.S. health spending rise.

PMID- 15452945
TI  - Abstracts of the 52nd Annual Scientific Meeting of the Irish Gerontological
      Society. 10-11 September 2004, University of Limerick.

PMID- 15452944
TI  - Most hospitals lack enough procedure volume to spot surgical quality problems.

PMID- 15452946
TI  - Abstracts of the 40th Annual Meeting of the European Association for the Study of
      Diabetes. Munich, Germany, 5-9 September 2004.

PMID- 15452947
TI  - Gap in drug coverage often causes lapses in adherence to drug regimen, study
      shows.

PMID- 15452948
TI  - Abstracts for the XIIth World Congress of Psychiatric Genetics. Dublin, Ireland,
      9-13 October 2004.

PMID- 15452949
TI  - Abstracts of the Congress of Nephrology 2004 joint scientific meeting. September
      18-21, 2004, Basel.

PMID- 15452950
TI  - Abstracts of the 37th Annual Meeting of the Society for the Study of
      Reproduction. August 1-4, 2004, Vancouver, Canada.

PMID- 15452951
TI  - Hazard or help?

PMID- 15452952
TI  - Slow recovery in Peru.

PMID- 15452953
TI  - Prediction of the disulfide-bonding state of cysteines in proteins at 88%
      accuracy.

PMID- 15452954
TI  - Redox and photoactive dendrimers in solution and on surfaces.

PMID- 15452955
TI  - Ion channel based on artificial receptors.

PMID- 15452956
TI  - Nuclear medicine makes news at SNM Annual Meeting.

PMID- 15452957
TI  - Michael J. Welch receives Cassen Award.

PMID- 15452958
TI  - Patch clamping moves to chips.

PMID- 15452959
TI  - Aebersold Award presented to Hank F. Kung.

PMID- 15452960
TI  - Alavi achievements recognized with de Hevesy Award.

PMID- 15452961
TI  - Integrated proteomics systems bring the pieces together.

PMID- 15452962
TI  - Changes in the world of biomedical research are moving the field of "personalized
      medicine" from concept to reality.

PMID- 15452963
TI  - Abstracts of the XXIII annual European Society of Regional Anesthesia Congress.
      Athens, Greece, 8-11 September 2004.

PMID- 15452964
TI  - Abstracts of the 2004 APS Translational Research Conference: Immunological and
      Pathophysiological Mechanisms in Inflammatory Bowel Disease. September 8-11,
      2004, Colorado, USA.

PMID- 15452965
TI  - Abstracts of the 2004 APS Intersociety Meeting: The Integrative Biology of
      Exercise. October 6-9, 2004, Austin, Texas, USA.

PMID- 15452966
TI  - Official 2004-2005 directory of members of the Texas Dental Association.

PMID- 15452967
TI  - [Congress of the Association of Epidemiologists of French-Speaking Language
      (ADELF). Bordeaux, France, 15-17 September 2004. Abstracts].

PMID- 15452968
TI  - Abstracts of the European Association for Vision and Eye Research. September 24
      27, 2004, Vilamoura, Portugal.

PMID- 15452969
TI  - Abstracts from the 7th International ISSX Meeting. August 29-September 2, 2004.
      Vancouver, Canada.

PMID- 15452970
TI  - [Abstracts of the French Radiology Meeting (JFR). October 2-6, 2004, Paris,
      France].

PMID- 15452971
TI  - Abstracts of the 7th World Congress of Psycho-Oncology. August 25-28, 2004,
      Copenhagen, Denmark.

PMID- 15452972
TI  - Characterization by FTIR spectroscopy of the photoreduction of the primary
      quinone acceptor QA in photosystem II.
AB  - Molecular changes associated with the photoreduction of the primary quinone
      acceptor Qa of photosystem II have been characterized by Fourier transform
      infrared spectroscopy. This reaction was light-induced at room temperature on
      photosystem II membranes in the presence of hydroxylamine and diuron. A positive
      signal at 1478 cm-1 is assigned to the C---O stretching mode of the semiquinone
      anion, and can be correlated to the negative C=O mode(s) of the neutral QA at
      1645 cm-1 and/or 16 cm-1. Analogies with bacterial reaction center are found in
      the amide I absorption range at 1672 cm-1, 1653 cm-1 and 1630 cm-1. The
      stabilization of QA- does not result from a large protein conformation change,
      but involves perturbations of several amino acid vibrations. At 1658 cm-1, a
      negative feature sensitive to 1H-2H exchange is tentatively assigned to a NH2
      histidine mode, while tryptophan D2252 could contribute to the signal at
      1560/1550 cm-1.

PMID- 15452974
TI  - Abstracts of the 6th Congress of the European Federation of National Associations
      of Orthopaedics and Traumatology. Helsinki, Finland, 4-10 June 2003.

PMID- 15452973
TI  - LACTRIMS 2004. Abstracts of the Latin American Committee for Treatment and
      Research in Multiple Sclerosis. Iguassu Falls, Brazil, August 25-28, 2004.

PMID- 15452975
TI  - Ferredoxin-dependent methane formation from acetate in cell extracts of
      Methanosarcina barkeri (strain MS).
AB  - Cell extracts of Methanosarcina barkeri grown on acetate catalyzed the conversion
      of acetyl-CoA to CO2 and CH4 at a specific rate of 50 nmol min-1 mg-1. When
      ferredoxin was removed from the extracts by DEAE-Sephacel anion exchange
      chromatography, the extracts were inactive but full activity was restored upon
      addition of purified ferredoxin from M. barkeri or from Clostridium pasteurianum.
      The apparent Km for ferredoxin from M. barkeri was determined to be 2.5 M. A
      ferredoxin dependence was also found for the formation of CO2, H2 and
      methylcoenzyme M from acetyl-CoA, when methane formation was inhibited by
      bromoethanesulfonate. Reduction of methyl-coenzyme M with H2 did not require
      ferredoxin. These and other data indicate that ferredoxin is involved as electron
      carrier in methanogenesis from acetate. Methanogenesis from acetyl-CoA in cell
      extracts was not dependent on the membrane fraction, which contains the
      cytochromes.

PMID- 15452976
TI  - Tissue-specific and differential expression of prothymosin alpha gene during rat
      development.
AB  - We have analyzed the RNA expression of prothymosin alpha (ProT alpha) gene during
      rat development in several tissues and compared it to that of two proteins
      related to cell proliferation: proliferating cell nuclear antigen (PCNA)/cyclin
      and histone H3 (H3). The expression of ProT alpha gene was found to be regulated
      in a developmental and tissue-specific manner. The mRNA levels of ProT alpha
      followed a similar time-course in liver, brain, kidney, and testis, being highly
      increased in the early periods of postnatal development. However, in thymus ProT
      alpha mRNA showed only moderate changes throughout development. Our findings
      suggest that ProT alpha participates in developmental processes like cell
      proliferation and/or differentiation.

PMID- 15452977
TI  - [Algorithm development for airway management].

PMID- 15452978
TI  - [How can one miss the correction local perfusion?].

PMID- 15452979
TI  - [Methods and instrumentation--intubation and intubation devices].

PMID- 15452980
TI  - [Progress in the prevention of typhoid fever in China].

PMID- 15452981
TI  - [Advances in the research on the epidemiology of occupational accidents].

PMID- 15452982
TI  - [Progress in the study of epidemiology of maternal-infant transmission of AIDS
      virus].

PMID- 15452983
TI  - Life without glasses.

PMID- 15452984
TI  - [Early identification of patients with acute pancreatitis at risk of critical
      deterioration: a multiparameter case-control study].
AB  - The aim of the study was the early identification of patients with acute
      pancreatitis who subsequently developed critical complications. All patients
      admitted to a surgical ward for acute pancreatitis were recruited into the study.
      The severity of acute pancreatitis was assessed using Ranson and Balthazar
      scores. Patients transferred to the intensive care unit (Group A) were matched
      with patients with the same scores who did not require intensive care treatment
      (Group B). Several clinical and biochemical variables were compared between the
      two groups. A total of 221 patients were recruited (110 m, 121 f; mean age: 60.6
      years; range: 17-94 years). Group A included 13 patients (7 m, 6 f; mean age:
      59.6 +/- 13.5 years; range: 35-76), whereas Group B included 27 patients (11 m,
      16 f; mean age 60.8 +/- 5.5 years; range: 44-93). Only glycaemia, pH, white cell
      count and body mass index differed between the two groups. The mortality rates
      were 31% in Group A and 7.4% in Group B, respectively (P<0.005) In the logistic
      regression analysis, only body mass index continued to show a significant
      difference. In this population of patients with acute pancreatitis, only body
      mass index proved capable of identifying patients at risk of critical
      complications.

PMID- 15452986
TI  - [Laparoscopic Heller myotomy with angle of His reconstruction: an alternative
      technique to partial fundoplication in the treatment of achalasia].
AB  - The aim of the study was to assess laparoscopic myotomy associated with angle of
      His reconstruction as an antireflux procedure in the treatment of achalasia.
      Thirty-one patients underwent a laparoscopic Heller myotomy; in 17 cases this was
      combined with an anterior partial funduplication, while in 14 cases the angle of
      His was reconstructed as an antireflux procedure. No postoperative morbidity or
      mortality were recorded in either group. and no statistical significance was
      found between the two groups in terms of recurrent dysphagia, postoperative
      reflux or medical therapy. In conclusion, enhancing the angle of His as an
      antireflux mechanism proved as effective as partial anterior fundoplication in
      reducing the incidence of recurrent achalasia.

PMID- 15452985
TI  - [Hiatal hernia, gastro-oesophageal reflux and oesophagitis: videofluorographic,
      endoscopic and histopathological correlation].
AB  - The aim of the study was to evaluate the correlation between hiatal hernia and
      gastro-oesophageal reflux and related histological abnormalities in patients
      without endoscopic oesophagitis. A consecutive series of 78 patients with a
      history of gastro-oesophageal reflux symptoms and hiatal hernia, as defined by
      videofluorography combined with a water siphon test, underwent
      oesophagogastroduodenoscopy and multiple biopsies. Hiatal hernia was confirmed
      endoscopically in 99% of cases. The water siphon test was positive for reflux in
      72% of cases. At endoscopy 42% of patients had oesophagitis and/or Barrett's
      oesophagus and 58% had no lesions. In the group without endoscopic lesions, at
      histology oesophagitis-related alterations were found in 98% and intestinal
      metaplasia in 27%. In conclusion, this study shows that symptomatic gastro
      oesophageal reflux patients with radiologically defined hiatal hernia should
      undergo endoscopy with multiple biopsies above the squamocolumnar junction, even
      when endoscopy is normal. This is in order to detect histological gastro
      oesophageal-reflux-related alterations, above all, when a positive water siphon
      test is also present, owing to its known correlation with intestinal metaplasia.

PMID- 15452987
TI  - [Digital cineradiology in the diagnosis and surgical treatment of pharyngo
      oesophageal junction motor disorders].
AB  - The aim of the study was to report our experience with the use of radiology in
      functional disorders of the cricopharyngeal muscle and their surgical therapy
      using digital cineradiology. Five-hundred and seventy dysphagic patients
      underwent dynamic study of the oral and pharyngeal phases of swallowing
      (Videofluoroscopic Swallowing Study, VFSS). A motor disorder of the
      cricopharyngeal muscle was diagnosed by videofluorography in 19 patients: the
      disorder was mild in 8, moderate in 7 and severe in 4. Two of these underwent
      cricopharyngeal myotomy, with an improvement in their dysphagia and swallowing
      mechanisms. VFSS provides a morphological and functional view of the aero
      digestive tracts: this is essential in the diagnosis of cricopharyngeal
      dysfunction and is capable of revealing the related laryngeal penetration and
      tracheal aspiration. VFSS must always include an oesophageal phase study because
      of the known clinical and physico-pathological correlations between the gastro
      oesophageal junction and the upper oesophageal sphincter. On the basis of our
      experience we believe that VFSS could be used as a primary investigation,
      followed by motility studies, and that it may be a useful complementary procedure
      both in the diagnosis of pharyngo-oesophageal junction motor disorders and with a
      view to surgical indications.

PMID- 15452989
TI  - [PATE 2000 Sorrento: a modern, effective instrument for defining haemorrhoids. A
      multicentre observational study conducted in 930 symptomatic patients].
AB  - In 2000, the Italian Society of Coloproctology and the UCP (Coloproctology Units)
      devised a new haemorrhoid classification system, named PATE 2000 Sorrento, which
      is capable of defining all the main characteristics of the disease. Any new
      system should be able to predict the real extent of hemorrhoids by means of a
      specific index in order to help physicians in choosing the best therapeutic
      option. The authors present the results of a national multicentre study of 930
      patients with symptomatic haemorrhoids. Nineteen patients (2%) could not be
      classified with the old haemorrhoid classification, while PATE 2000 Sorrento
      proved successful in classifying all patients. The difference was statistically
      significant. The new classification enables us to establish a specific score for
      the disease. In order to better evaluate the clinical impact of the scores
      obtained with PATE 2000 Sorrento, the authors analyzed the correlation between
      the score itself and the therapy chosen by each individual centre. The highest
      scores always corresponded to the choice of surgical hemorrhoidectomy, while in
      the case of lower values each centre seemed to be in doubt between medical
      therapy and other less invasive procedure such as sclerotherapy or rubber band
      ligation. These data were statistically significant (P < 0.0001). On the basis of
      our findings, PATE 2000 Sorrento seems to confirm its scientific and clinical
      relevance and could be a useful tool for the choice of the best treatment for
      each individual patient.

PMID- 15452988
TI  - Locally advanced thyroid cancer: therapeutic options.
AB  - The authors report on their experience in the management of thyroid cancer, with
      specific regard to advanced disease. Thyroid carcinomas behave differently
      according to: pathology, sex, age, grading and size. Differentiated lesions have
      a favourable outlook, while for less-differentiated tumours the prognosis is
      dismal. Extent of resection, lymphectomy technique and management of advanced
      disease remain matters of debate. Of particular interest are those neoplasms
      invading the upper aerodigestive tract, characterised by a worse prognosis in the
      case of differentiated tumours (1-6%), indicating an exceedingly aggressive
      behaviour in what is usually a slowly evolving disease. Surgery, with a curative
      intent or for palliation, is mandatory. The tumour progressively invades the
      tracheal lumen and is seldom manageable by alternative, non-surgical methods, and
      in any case only for short periods of time. Total thyroidectomy with tracheal
      resection and anastomosis is the surgical technique of choice and, when combined
      with radiometabolic therapy and/or external radiotherapy, yields survival data
      comparable with those relating to less advanced differentiated lesions. Tracheal
      stents and tracheotomy improve the quality of life. Laser therapy is indicated in
      cases of asphyxia, and as a preliminary step with a view to subsequent radical or
      palliative treatments.

PMID- 15452990
TI  - [Tubulo-villous rectal tumours. Results of surgical resection in relation to
      histotype (30 years' experience)].
AB  - Adenomas of the rectum are frequently found during endoscopic examination. We
      report on our 30 years of experience with the treatment of tubulo-villous
      adenomas based on histotype. Between 1971 and 2001, 104 villous tumours of the
      rectum were treated surgically. The patients' average age was 65 years. These
      were sessile tumours in 69% of cases, pedunculated in 17.5% and flowing tumours
      in 13.5%. The mean tumour size was 3 cm. They were associated with colon cancer
      in 15% of cases and with polyadenoma in 10%. They were located in the rectum
      within 0 to 6 cm of the anal margin in half the cases. These tumours were treated
      by local excision in 74 cases and by wide excision in 30 cases. The malignant
      potential of the tumours was 30%, including 10% invasive malignancy. There were
      no surgical fatalities, but a 6% medical fatality rate was registered. There was
      a 20% complication rate related to the surgical technique. Twenty patients were
      lost to follow-up. Out of 84 villous tumours, monitored over a mean survival
      period of 6.5 years, there were 24 recurrences: 18 underwent endoscopic excision
      and in 6 cases a wide resection. The various tumour resection techniques and the
      operative indications of variable difficulty are presented. It would seem, at
      present, that total resection of the rectum with a colo-anal anastomosis is the
      best treatment for large flowing villous tumours occupying almost the entire
      rectum. Thorough preoperative examination and the mastering of various surgical
      procedures should allow the most suitable choice of treatment for each individual
      case.

PMID- 15452991
TI  - Complex anal fistula surgery: personal experience.
AB  - Personal experience with the treatment cryptogenic complex anal fistulas over the
      10-year period from 1993 to 2002 is reported. Such fistulas accounted for 54 out
      of 255 fistulas observed (21.1%). Accurate anatomo-pathological classification,
      based on the connections between the fistulas and the sphincter and the
      musculature of the pelvic floor, is mandatory, as is thorough preoperative
      evaluation of ano-rectal function and of the risk of faecal incontinence. The
      surgical strategies used, in relation to the different kinds of complex fistulas
      treated, are schematically reported. A mixed technique consisting in fistulectomy
      fistulotomy with setons was particularly preferred, because of the risk related
      to immediate dissection of the sphincter, especially when concurrent risk factors
      are present. As regards the results obtained, the surgical outcome consisted in
      healing in 49/54 cases (90.7%) as against recurrence or persistence of the
      fistula in 5/54 (9.3%). Minor complications occurred in 6/54 (11.1%); no major
      complications were observed and no cases of permanent faecal incontinence were
      reported. In conclusion, the surgical choice in cases of complex fistulas must
      lead to definitive, radical treatment of the lesion, at the same time avoiding
      irreversible anal incontinence due to severe lesions to the sphincter.

PMID- 15452992
TI  - [New abdominal wall reconstruction technique with a plastic-rehabilitative intent
      (back pain improvement)].
AB  - Many abdominal wall reconstruction techniques have generally failed to pay
      attention to a number of anatomical considerations concerning the continuity of
      the thoraco-lumboabdominal fascia that envelops the dorsal and ventral muscles.
      We have introduced a new surgical technique (round mesh) developed to improve the
      abdominal wall weakness or pathology (hernia, laparocele) with the aim of
      restoring the muscular synergy between the anterior and posterior trunk
      compartments, thus improving sacroiliac stability, posture, and standing effort
      endurance. One hundred patients of both sexes were enrolled in this
      investigation. All were affected by abdominal wall impairment, frank hernia or
      laparocele, and had been complaining of lumbar and sciatic pain for long periods
      without any definite intervertebral disk pathology. They underwent pre- and
      postoperative subjective and objective evaluation and insertion of a prefascial
      polypropylene mesh with a posterior martingale that passes across the spine and
      paravertebral muscles, ending in two wider rectangles that are criss-crossed
      ventrally and finally sutured to the iliopubic brim. All the patients improved
      either subjectively or objectively with the round mesh procedure. This new
      technique is particularly useful in cases of reduction or impairment of the recti
      abdominis, transverse and oblique muscles, because simple suture and plication of
      these muscles is no guarantee of long-term functional restoration.

PMID- 15452993
TI  - [Disposable isostatic anal retractor: results of a clinical assessment].
AB  - In this paper the authors present the technical characteristics and clinical
      results of a new anal retractor designed and produced by them. This new
      instrument, made of disposable material, allows the proctologist to operate
      completely alone thanks to a system of rotating rings which are fixed directly to
      the patient's legs by means of Velcro bands. Twenty consecutive patients with
      proctological diseases have been operated on to date with the new device. No
      complications were registered in our series. The rotation movement and overall
      stability of the retractor were judged sufficient in 6 cases and good in 14.
      Opening of the device proved asymmetrical in 20% of the cases without this
      affecting the surgical technique. Our surgical team considered the prototype
      ideal, and the operative space available to the surgeon much greater than with
      previous retractor models. No limitations have been observed in treating any of
      the proctological diseases. The possibility of performing sutures in the anal
      canal was judged to be good. In conclusion, our new anal retractor would appear
      to guarantee greater autonomy in proctological surgery with much better clinical
      and therapeutic results and lower costs.

PMID- 15452994
TI  - [Laparoscopic treatment of incisional hernia with Parietex mesh. Preliminary
      results and review of the literature].
AB  - Conventional surgery for incisional hernia carries a postoperative morbidity and
      recurrence rate of more than 12%. The aim of this study was to report our
      experience with the laparoscopic treatment of incisional hernia with the use of a
      composite mesh (Parietex, Sofradim, Celbio). The median duration of the operation
      was 135 minutes. In one patient peritonitis from small bowel perforation occurred
      on postoperative day 2 and required emergency surgery. The median postoperative
      hospital stay was 3 days. No complications were observed over a median follow-up
      period of 12 months. The goal of the laparoscopic treatment of incisional hernia
      is to decrease the incidence of local complications and the recurrence rate which
      are seen with traditional open surgery. To this should be added all the
      advantages of minimally invasive surgery in terms of decreased postoperative
      pain, length of hospital stay, and sick leave.

PMID- 15452995
TI  - [Anatomical thyroid abnormalities. Quadrilobate thyroid gland: a case report and
      review of the literature].
AB  - Abnormalities of the thyroid gland and of some adjacent structures arouse
      interest because of their surgical implications. One need only think of a non
      recurrent laryngeal nerve, of thyroid hemiagenesis or of a quadrilobate thyroid
      gland, as in the case described here. To the best of the authors' knowledge, no
      similar reports of such a case are present in the medical literature. The patient
      was a 37-year-old woman suffering from Graves' disease. The abnormality was
      detected only during surgical examination and consisted in two lobes divided by a
      cleft on each side and joined by an isthmus. After a number of considerations
      regarding the anatomical details of this case and a review of the literature, the
      authors attempt to give an embryological interpretation and formulate the
      hypothesis that the second lateral lobe could be a development of the widely
      studied and controversial embryological anlage, the so-called "lateral thyroid".

PMID- 15452996
TI  - [Hashimoto's thyroiditis and medullary carcinoma in the same gland: a purely
      random occurrence?].
AB  - In this paper the authors describe the case of 64-year-old woman who had been
      suffering from poorly defined thyroid disease for 30 years and Hashimoto's
      thyroiditis for 3 years, with recent detection of high serum calcitonin and CEA.
      Her family history was negative for endocrinological diseases and her general
      medical history was not significant for any diseases, except for mild
      hypertension. There were no pathological findings at physical examination.
      Cervical ultrasound showed 2 nodular lesions of the right lobe of the thyroid and
      the isthmus. FNABs of these nodules were performed under ultrasound control and
      proved non-diagnostic. The patient underwent total thyroidectomy. Intra-operative
      frozen sections were negative for cancer. Definitive histological examination was
      positive for medullary carcinoma of the right thyroid lobe (diameter 0.6 cm) in
      Hashimoto's thyroiditis. The association between thyroid cancers deriving from
      follicular cells and Hashimoto's thyroiditis is documented in the literature and
      would appear to determine a better prognosis. Cases such as the one presented in
      this paper, however, are rare and it is debated whether lymphocyte infiltration
      may predispose to the onset of medullary carcinoma or whether it is a defence
      against the tumour.

PMID- 15452997
TI  - Percutaneous drainage and surgery for splenic abscess: a case report.
AB  - Splenic abscess is a rare clinical entity; however, thanks to the refinement of
      diagnostic techniques and to the increase of population at risk its presence is
      discovered more frequently. In our ward we evaluated a patient by ematochimical
      and bacteriological exams and abdomen CT. After antibiotical therapy and
      percutaneous drainage the patient was discharged on the fifteenth day. One month
      later the patient returned to our emergency room: for the presence of two
      intrasplenic lesions; he underwent splenectomy. Six month after the operation,
      the patient was healty. The two methods (surgery and radiological drainage)
      cannot be compared because the indications are different. Therefore a
      progressively invasive therapeutic approach would appear to be indicated. If this
      not successful, splenectomy performed whit laparoscopic or laparotomic techniques
      should follow.

PMID- 15452998
TI  - Solitary necrotic nodule of the liver: diagnostic and therapeutic considerations
      regarding a case.
AB  - Solitary necrotic nodule is a rare benign lesion of the liver of unknown
      aetiology, which as a result of its radiological features can be misdiagnosed as
      a necrotic tumour. We believe that surgical exploration with a limited liver
      resection and an extemporary examination of the specimen is the best strategy for
      this rare type of lesion.

PMID- 15452999
TI  - Hepatocarcinoma, gallstone disease and gallbladder carcinoma: a case report of a
      rare incidental association.
AB  - We report a rare case of a patient operated on with a diagnosis of hepatic tumour
      and gallstone disease, which postoperatively was found to be a hepatocellular
      carcinoma associated with a gallbladder carcinoma. Spiral CT at admission showed
      only a hepatic mass in the 4th segment, compatible with hepatocellular carcinoma
      and gallbladder lithiasis. Cholecystectomy was performed followed by a wedge
      resection of the 4th segment of the liver. The histopathological examination
      revealed a well-differentiated hepatocellular carcinoma and, surprisingly, an
      adenocarcinoma of the gallbladder confined to the mucosa. The association of a
      hepatocellular carcinoma and gallbladder adenocarcinoma is extremely rare. This
      association, together with an analysis of the literature showing the increased
      incidence of gallstones in cirrhotic patients and the consequent greater surgical
      risk when undergoing subsequent cholecystectomy after liver resection, would
      suggest that cholecystectomy should be performed routinely during liver resection
      for hepatocellular carcinoma or cirrhosis, even for minor resections and when
      there are no evident signs of gallbladder disease.

PMID- 15453000
TI  - Wireless capsule endoscopy in a case of small bowell obstruction: not always
      contraindicated.
AB  - Wireless capsule endoscopy is a new diagnostic technique used especially for
      investigating the entire small bowel. Recent studies have demonstrated its
      superior ability to detect and evaluate small bowel lesions compared to other
      radiological examinations. Performing video capsule endoscopy is regarded as
      contraindicated when an intestinal occlusion is documented. We present a case of
      hidden intestinal bleeding which underwent wireless capsule endoscopy and was
      treated successfully despite documented ileal stenosis.

PMID- 15453001
TI  - [Carney's syndrome: a case report].
AB  - The peculiar aspects of the clinico-pathological picture and surgical treatment
      of Carney's syndrome, a rare morbid association of multiple non-epithelial
      neoplasms of the stomach, lung and chromaffin tissue, are focused on and
      discussed on the basis of the observation of a clinical case. The patient was a
      22-year-old male with a multiple stromal tumour of the stomach, oesophageal
      leiomyoma, a left thoracic terato-chondroid neoplasm and gallbladder adenomyoma,
      surgically treated in two stages: laparotomy for gastric resection and
      cholecystectomy followed by left thoracotomy for resection of the intrathoracic
      neoplasm and excision of the oesophageal leiomyoma. The postoperative course was
      characterised by low morbidity and healing was monitored by means of thorough
      follow-up examinations. The case reported here is classed among the variants of
      Carney's classical triad. A knowledge of the pathological associations of these
      uncommon tumours and their natural history is of great importance for
      implementing appropriate diagnostic and therapeutic protocols.

PMID- 15453002
TI  - [Intralobar pulmonary sequestration: a case report].
AB  - The authors report a case of intralobar pulmonary sequestration diagnosed
      accidentally in a 64-year-old woman. The patient subsequently underwent surgery.
      The authors were prompted by this fairly rare case to describe and discuss its
      anatomopathological, clinical, diagnostic and therapeutic aspects.

PMID- 15453003
TI  - Special delivery: when the pills "absolutely, positively" can't be delivered at
      home.
AB  - The practice of storing and dispensing medications by providers at an inner city
      neighborhood health center that serves predominantly ethnic minority clients was
      terminated due to accreditation regulations. This practice promoted adherence
      since many clients did not want to receive medications by mail at home due to
      confidentiality concerns or were unwilling to present to their local pharmacy due
      to fear of discrimination related to HIV status. The purpose of this paper is to
      describe an alternative means to access HIV medications in a safe and supportive
      environment for clients confronted with cultural and social barriers through a
      unique collaboration between an HIV specialty care program and HIV specialty
      pharmacy.

PMID- 15453004
TI  - Context and common ground: cultural adaptation of an intervention for minority
      HIV infected individuals.
AB  - Understanding social contextual mediators of risk in HIV/AIDS prevention and
      promoting cultural adaptation of clinical interventions have evolved from new
      priorities set forth by the National Institutes of Health (NIH) on ecological
      validity and translational research (NIH, 2001). Thus, emphasis is placed on
      linguistically and culturally translating promising interventions "for and with"
      new populations to serve the realities of the particular group. The purpose of
      this paper is to describe the process involved in developing culturally sensitive
      interventions to strengthen the ecological validity of a cognitive behavioral
      stress management (CBSM) intervention for HIV+ individuals.

PMID- 15453005
TI  - Mothers' voices: culturally diverse mothers' experiences talking with their
      children about HIV/AIDS.
AB  - A qualitative analysis of culturally diverse mothers' experiences communicating
      with their children about HIV/AIDS following their participation in a nationally
      renowned prevention and education program illuminated some of the challenges and
      surprises these women encountered. Excerpts of "Mothers' Voices" illustrate the
      themes that emerged through data analysis. Implications and applications to other
      contexts are provided.

PMID- 15453006
TI  - Culturally relevant HIV interventions: transcending ethnicity.
AB  - Over the last 2 years, the co-authors produced an HIV prevention film for teens
      in collaboration with four African American women living with HIV. However, there
      were initially concerns that the experiences and prevention messages in the film
      would not be relevant to women of other cultures and ethnic backgrounds.
      Pretesting of the film was completed with African American and Latina teen girls;
      adult women who were HIV providers of various ethnicities and cultures; and adult
      Latina, Cape Verdean, and White women as well as adult Haitian men and women.
      Findings indicated that cultural relevance was strong for individuals who shared
      gender identity and socioeconomic status.

PMID- 15453007
TI  - Unmet need: what justifies the search for a new antidepressant?
AB  - The burden of major depressive disorder is huge, as is clearly documented by
      World Health Organization data. A major component of this burden is the episodic
      nature of depression. Depressive episodes may be precipitated by stress and if
      left untreated can become episodic, recurrent, and chronic. Hippocampal atrophy
      may be a consequence of chronic depression, but antidepressants and mood
      stabilizers have been suggested to prevent or reverse this damage. Adequate
      treatment is essential for preventing depression from becoming chronic.
      Unfortunately, current antidepressant treatments fall short of being adequate for
      many patients. Shortcomings such as low remission/high treatment-resistance
      rates, slow onset of action, side effects, and drug-drug interactions influence
      patient adherence, which may be as low as 56% after the first 3 months of
      treatment. Since many patients may need long-term antidepressant treatment, new
      antidepressants need to be developed that are effective, tolerable, and safe and
      that improve maintenance of wellness.

PMID- 15453008
TI  - Factors contributing to failed trials of new agents: can technology prevent some
      problems?
AB  - For psychiatry to contribute to the development of the next generation of
      antidepressant pharmacotherapies, effective use of clinical trial methods is as
      critical as innovation in neurochemical research. Results from clinical trials on
      the efficacy of a new drug can be obscured by methodological problems. Accurate
      diagnosis and precise measurement of the clinical symptoms during conduct of the
      clinical trials are crucial to obtaining interpretable outcomes. As tools that
      reliably diagnose disorders and assess symptoms become available, computer
      administration of rating instruments may improve the accuracy of clinical trial
      results. This article describes methodological factors that can confound study
      outcomes and discusses the potential for interactive voice response (IVR)
      technology to address some of these problems.

PMID- 15453009
TI  - Can monoamine-based therapies be improved?
AB  - Monoamine-based therapies that selectively target serotonin, norepinephrine, or
      dopamine uptake are effective as antidepressants. However, many depressed
      patients do not achieve remission with these single-action agents. Treatment
      strategies that target more than one neurotransmitter, either through
      augmentation, combination treatment, or the development of single agents with
      dual or triple reuptake mechanisms, may prove to be even more effective than
      traditional antidepressants and merit further research.

PMID- 15453010
TI  - Beyond monoamine-based therapies: clues to new approaches.
AB  - Advances in antidepressant therapy have resulted in agents with fewer serious
      side effects than, for example, nonselective monoamine oxidase inhibitors and
      tricyclic antidepressants. Nonetheless, these newer agents are far from the
      ideal. Many of the drawbacks associated with these newer agents--slow onset, low
      rate of response, and low rate of remission--are likely to be mechanism related.
      In order to overcome these problems, researchers must either improve upon these
      traditional, biogenic amine-based mechanisms or explore nontraditional
      mechanisms. Strategies for improving biogenic amine-based antidepressants include
      the so-called serotonin augmentation strategy and the broad spectrum agent that
      simultaneously blocks reuptake at the serotonin, norepinephrine, and dopamine
      transporters. Two nontraditional approaches employ modulation of glutamate
      receptor function. At face value, these glutamate-based approaches (N-methyl-D
      aspartate [NMDA] antagonists and alpha-amino-3-hydroxy-5-methyl-4-isoxazole
      propionic acid [AMPA] receptor potentiators) appear diametrically opposed.
      However, these 2 mechanisms may ultimately impact similar cellular endpoints.

PMID- 15453011
TI  - Studying new antidepressants: if there were a light at the end of the tunnel,
      could we see it?
AB  - This commentary began with the proposition that the SSRIs have become the
      standard of comparison for new antidepressants. It is also suggested that the
      conventional wisdom that all antidepressants are equally effective is no longer
      true. Rather, it is asserted that the same factors that have compromised the
      sensitivity of RCTs to detect drug-placebo differences similarly have impaired
      discriminations between effective and even more effective antidepressants. In
      order to have the power to make such a distinction, an RCT may need to enroll 300
      or more patients per cell. Few studies thus have adequate statistical power.
      Alternatively, conclusions can be drawn from quantitative methods that combine
      data from groups of smaller studies. The relative merits and limitations of 2
      strategies used to examine the results of comparative studies, meta-analysis and
      pooled analysis, were discussed. The former method is preferred when there are a
      large number of relevant RCTs; however, failure to include unpublished data from
      all relevant studies may inflate results. The latter method, unless biased by
      selective inclusion of studies or marked heterogeneity of results, is preferred
      when there are only a handful of comparable studies. Although the task of
      selecting among a number of good choices remains more clinical art than science,
      quantitative methods are now available to help determine if there are clinically
      meaningful differences in antidepressant efficacy. The conventional RCT provides
      a low power telescope for visualizing differences between effective medications.
      If there were a light at the end of the tunnel, it would be difficult to see it.
      Until methods that can improve the ability to discriminate between an active
      antidepressant and a placebo are identified and implemented, the ability to see
      modest differences necessitates the use of statistical methods such as meta
      analysis and pooled analysis of original data.

PMID- 15453012
TI  - Molar extraction and utility arches.

PMID- 15453013
TI  - The fixed sagittal appliance.

PMID- 15453014
TI  - Intraoral orthotics for treatment of TMD.

PMID- 15453015
TI  - Why some cases of mandibular advancement fail.

PMID- 15453016
TI  - Use of the BEST-BITE anterior discluder for the treatment of migraine headache: a
      case study.

PMID- 15453017
TI  - The promise.

PMID- 15453018
TI  - Contexts for the study of the economic influence of nursing diagnoses on patient
      outcomes.
AB  - PURPOSE: To examine the historical, legal/ organizational, informatics, clinical,
      economic, and policy contexts underlying economic consequences of nursing
      diagnoses on patient outcomes. DATA SOURCES: Published literature, online
      material. DATA SYNTHESIS: Nursing diagnoses influence diagnostic-specific patient
      outcomes and other outcome variables such as length of hospital stay, morbidity,
      and mortality. CONCLUSIONS: Examination of the economic ramifications of nursing
      diagnosis on patient outcomes can be facilitated using standardized language and
      databases containing nursing-sensitive measures.

PMID- 15453019
TI  - Diagnostic-specific outcomes and nursing effectiveness research.
AB  - PURPOSE: To review the use of diagnosis-specific outcomes in health care and
      nursing. DATA SOURCES: Published literature, information databases. DATA
      SYNTHESIS: The need to identify nursing diagnosis-specific outcomes is necessary
      in order to expand nursing's knowledge base and identify the cost-effectiveness
      of nursing interventions. CONCLUSIONS: Outcomes work needs to be done across
      settings where care is provided. PRACTICE IMPLICATIONS: Outcomes information is
      necessary to identify the cost and impact of nursing interventions.

PMID- 15453020
TI  - [Is non alcoholic steatohepatitis (NASH) part of the metabolic syndrome?].
AB  - The metabolic syndrome is one of the most common disease of our era that may
      cause numerous complications. There are some studies showing the need to take
      attention to the hepatic manifestation of the metabolic syndrome besides its
      already well-known consequences. In most of the cases there are histopathological
      evidences for the presence of fatty liver and mainly non alcoholic
      steatohepatitis. These conditions can lead to hepatic cirrhosis, hepatic failure
      or even to hepatocellular carcinoma. The risk of these consequences is the
      greater the more severe the metabolic syndrome is and the more components of it
      are included. All these emphasise the importance of examining the hepathological
      status of the patients suffering from the metabolic syndrome.

PMID- 15453021
TI  - [Endobronchial ultrasonography in postintubation tracheal stenosis].
AB  - INTRODUCTION: The correct evaluation of the tracheal wall's structure is
      necessary for the management of postintubation tracheal stenosis (PTS).
      Endobronchial ultrasonography (EBUS) is suitable for visualisation of layers of
      the tracheal wall and the assessment of cartilages' damage. AIM: The authors
      assessed the usefulness of EBUS in the anatomical characterization of PTS and in
      the decision making in its therapy. PATIENTS, METHODS: Between March 2002, and
      September 2003, 22 patients with PTS were examined by bronchoscopy together with
      EBUS. RESULTS: 13 patients had complex stenosis and from them destruction of
      tracheal cartilage was demonstrated in 5 patients. Of them bronchoscopic
      intervention resulted in only short term symptom free period in 3 patients.
      CONCLUSION: The destruction of tracheal cartilage detected by EBUS might be an
      indication for an early surgical intervention. According to author's results EBUS
      can be a useful method in evaluation of PTS.

PMID- 15453022
TI  - [Fetal renal ultrasound investigation in toxaemic pregnancies].
AB  - INTRODUCTION: A relationship was sought between renal hyperechogenicity and the
      hypoxic state of fetuses. MATERIAL AND METHODS: 120 pathological pregnancies were
      examined between the 28th and 36th weeks. The echogenicity of the fetal kidneys
      was examined with Combison 530 3D ultrasound equipment fitted with a 3-5 MHz
      transabdominal transducer. The serum kidney and liver functions and plasma
      electrolytes of the mothers were examined and blood was collected from the
      pulsating umbilical artery for determination of the same serum parameters. After
      delivery, the physical condition of the neonates was followed and their kidneys
      were examined with the same ultrasound equipment within the first 5 days.
      RESULTS: There was a significant difference between the cases with fetal renal
      hyperechogenicity and without it for the pathological neonatal clinical outcome
      (chi-square test with Yates correction, p < 0.01). There were significantly more
      intrauterine retarded fetuses (6 cases, 40%) in cases with fetal renal
      hyperechogenicity, than in the control group (3 cases, 3%). The mode of delivery
      was caesarean section in 7 cases (46%) in group with fetal renal
      hyperechogenicity, while it were 6 cases (6%) in control group. The risk for
      pathological outcome is 6 times more in cases with fetal renal hyperechogenicity.
      CONCLUSION: The results demonstrate that fetuses exhibiting renal
      hyperechogenicity in pathological pregnancies require particularly careful
      obstetric control and neonatological consultation. It is important that
      hyperechogenic cases be admitted to a perinatal intensive care unit. Fetal renal
      hyperechogenicity is considered to be associated with an enhanced risk of adverse
      perinatal outcome.

PMID- 15453023
TI  - [Informed consent: a pragmatic view].
AB  - The author highlights some pragmatic aspects of informed consent that could help
      to bridge the gap between the currently valid legal requirements and the
      practical realities of providing medical information in Hungarian health-care
      settings. One of the crucial point of informed consent is whether the patient
      properly understood the provided medical information. Consequently, effective
      communication becomes an inevitable condition of providing informed consent. The
      results and insights coming from psychological research--concerning lay
      understanding of medical information, of the readability of consent forms, and
      especially of the lay understanding of statistical information, and risk
      communication--could help to create a better practice of medical communication
      that could satisfy both ethical and legal requirements. The author argues as well
      for creating more concrete and practically oriented guidelines concerning
      informed consent that would also help to increase the quality of medical
      information giving. These might help us approach the medical ideal that was
      conceptualised in the doctrine of informed consent.

PMID- 15453024
TI  - [Waardenburg syndrome].
AB  - The authors discuss the case of a patient suffering from an auditory-pigmentary
      syndrome. The patient in whom the Waardenburg syndrome had never been diagnosed
      before was observed because of another disease, which quite frequently causes
      hearing loss in childhood. In a short review of the literature, the authors
      describe the other components of the syndrome and the recent information about
      the genetic background of the disease.

PMID- 15453025
TI  - [Treatment of tension headache with depression].

PMID- 15453026
TI  - [Treatment of common cold].

PMID- 15453027
TI  - [Biological markers of hepatocellular carcinoma].
AB  - Hepatocellular carcinoma is a rapidly fatal tumor. The only hope for a cure lies
      in early diagnosis. It follows that an effective screening strategy should be
      used in high-risk populations. Screening currently relies on tumor markers such
      as alfa fetoprotein (AFP) and imaging modalities. Because the AFP assay lacks
      sensitivity and specificity in patient with small tumors, other serum markers are
      being evaluated.

PMID- 15453028
TI  - [Digestive parasitism in Sousse area. Results of a 16 years retrospective study].
AB  - To report the prevalence and type of intestinal parasites together with their
      kinetics in Sousse region. Our retrospective study concern data from the
      examination of 56,268 stool samples and 7552 tape tests, performed in the
      laboratory of parasitology of F. Hached Sousse hospital from 1st January 1987 up
      to 31 December 2002. We observed an overall parasite prevalence of 31.5%. Most
      common parasites were protozoa, Giardia lamblia, Dientamoeba fragilis and
      Blastocystis hominis being the most frequently encountered. Helminths consisted
      mainly of Enterobias vermicularis (35.86% positive tape tests) and Hymenolepis
      nanus. The kinetics data analysis showed an important decrease in the prevalence
      of Giardia lamblia, the other feco-oral transmitted flagellates and Hymenolepis
      nanus. In contrast, Dientamoeba fragilis and Blastocystis hominis prevalences
      increased. The prevalence of the amoeba showed a slight decrease. Intestinal
      parasites remain quite common in Sousse region, even though their epidemiological
      patterns are changing. Factors inducing these changes need to be investigated in
      order to plan efficient control measures.

PMID- 15453029
TI  - [Situations of conversion during laparoscopic cholecystectomy: series of 300
      cholecystectomies].
AB  - Laparoscopy is the "gold standard" for cholecystectomy, wherever it can happen
      that the surgeon must converse to laparotomy. The authors report 300 cases of
      laparoscopic cholecystectomy; the conversion rate was 9%; for cholecystitis
      (19%), cystic hemorrhage (3.7%) common bile duct (7.4%) and failure of material
      (11%). It resort from that study that laparoscopic cholecystectomy is safe,
      wherever it keeps some limits and conversion still remains a security and don't
      be assimilated to a failure.

PMID- 15453030
TI  - [Apport of serum vitamin B12 determination in the diagnosis of deficiency: about
      95 cases].
AB  - Vitamin B12 belong a group of cobalamins. It's known to be an enzymatic cofactor
      of many metabolic reactions essentially in the synthesis of DNA. Damage of
      deficiency are various essentially hematologic and neurologic. Macrocytic anaemia
      constitute the main disorder of vitamin B12 deficiency. However, Vitamin B12
      deficiency is common in the elderly with neuropsychiatric disorders whether
      macrocytic anaemia is present or not as its development may come later. In a
      study we investigate 95 patients aged 21 to 85 years (29 men, 20 women) with
      symptoms of vitamin B12 deficiency. First, vitamin B12 serum were measured by
      immuno enzymatic method (MEIA Abbott). Values were classified among 4 categories
      characterised on manufacture norms; low: 41 cases, unspecified: 19 cases, normal:
      13 cases and high: 22 cases. Secondly, the concordance between Vitamin B12 serum,
      clinical history and evolution were evaluated. The Kappa index established showed
      a satisfactory result (= 0.97).

PMID- 15453031
TI  - [Evaluation of electrocardiogram's interpretation in the emergency department].
AB  - The aim of this study was to determine the concordance of emergency physicians'
      and cardiologists' interpretations of emergency department (ED)
      electrocardiograms (ECG) and to evaluate the impact of ECG misinterpretation on
      patient management. From December 1993 to April 1994 one hundred ninety five ECG
      interpretations (3.3% of all consultants) were registered prospectively using a
      programmed-response data sheet. A second blinded interpretation by a cardiologist
      was performed and compared with the emergency physicians' interpretations. The
      overall concordance between emergency physicians' and cardiologist ECG
      interpretations was observed in 149 (76%) cases (kappa = 0.41). The concordance
      rate was lower in abnormal ECGs (kappa = 0.19). CONCLUSION: In our study, the
      quality of ECG interpretation by ED physicians is satisfactory and the rare
      misinterpretations have minimal clinical impact.

PMID- 15453032
TI  - [Pancreaticogastric anastomosis after pancreatic resection. About 40 cases].
AB  - The risk of pancreaticojejunal anastomosis fistulization represents the main
      factor of mortality and morbidity after pancreatic resection. The
      pancreatogastrostomy represents a technical alternative that can be achieved
      easily. The purpose of our study is to report our experience of this technique
      and to analyse respectively 40 pancreactogastric anastomosis after 29 cephalic
      duodenopancreatectomies and 11 corporeocaudal pancreatectomies. The operative
      sequelae have been characterized by 5 cases (12.5%) of digestive hemorrhages, 3
      cases (7.5%) of pancreatic fistula, 3 cases (7.5%) of intra-abdominal bleeding
      and a lymphorrhagia (2.5%). The operative mortality rate was about 5% (2 cases).
      These results are similar to the results reported in the literature by the users
      of this technique.

PMID- 15453033
TI  - [Acute renal failure due to drugs in diabetics patients].
AB  - Acute renal failure (ARF) in patients with diabetes mellitus is frequent. It is
      caused by several factors notably drugs. Our retrospective study includes 20
      cases of ARF induced by drugs in diabetic patients. Eleven men and 9 women with
      mean age of 55.2 years (17-71 years) were enrolled in the study. Type 2 diabetes
      mellitus was found in 18 cases and type 1 in 2 cases. Risk factors found are age
      more than 70 years in 17 cases, pre-existent renal failure in 17 cases,
      dehydratation in 6 cases, and drug association in 9 cases. In our study diuretics
      used solely or in association with other drugs were found to be the essential
      cause of ARF. ACE was noted in 5 cases, gentamycin in 2 cases, non-steroidal
      antiinflammatory drugs in 1 case, colimycin in 1 case and radiographic contrast
      media in 4 cases. Symptoms of hypersensitivity are fever in 3 cases, itchiness in
      2 case, hepatic dysfunction in 7 case, and hypereosinophilia in 3 cases. Oliguria
      was observed in 11 patients. Eight patients were dialyzed. Renal function
      recovery is total in 9 case and partial in 9 others. Two patients having oliguria
      died. CONCLUSION: Diuretics are the first cause of drug-induced ARF in diabetic
      patients. This ARF worsens the renal prognosis for these patients. Oliguria is
      high risk of mortality.

PMID- 15453034
TI  - [Echocardiography under perfusion with dobutamine. Experience of Tunisian
      cardiologic service. About 70 cases].
AB  - We report a prospective study which began on February 1st, 1999. 70 consecutive
      and non selected patients got dobutamine stress echocardiography. The major
      indication, in 53% of cases, was detection of coronary disease in patients
      suffering from chest pain but whose stress testing were not conclusive.
      Dobutamine was continuously and intravenously administered at doses ranging from
      5 to 40 microg. Maximal dose was obtained in 73% of cases. The most frequent
      reason that led us to stop the test was the reach of the target cardiac frequency
      (85 of FMT). We observed 7 severe rhythmic complications (2 auricular
      fibrillation, 1 flutter, 2 episodes of frequent and polymorphic ESV, 2 TVNS). One
      patient presented a myocardial infarction during dobutamine echography whereas
      the basic kinetics was normal. 26 patients got a coronarography within 3 days
      following echography. Stress echography detected a significant coronary stenosis
      (> or = 50%), with a sensitivity of 86%, a specificity of 83% and a precision in
      the diagnosis of 84%.

PMID- 15453035
TI  - [Non-specific interstitial pneumonia (NIP): diagnosis and prognosis].
AB  - The non-specific interstitial pneumonia (NIP) is an idiopathic diffuse
      interstitial pneumonia. It is recently reported by Katzenstein and Fiorelli in
      1994. The clinical features are mild comparing with usual interstitial pneumonia
      and its histological features include a predominant degree of interstitial
      inflammation and a rare areas of honey combing, the lesions are temporally
      uniform. We reported a case of 32 year-old woman with non-specific interstitial
      pneumonia. The diagnosis was based on histological criteria. The authors discuses
      the diagnosis and the prognosis of this recent entity.

PMID- 15453036
TI  - [Bronchectasis in Horton's disease: fortuitous association?].
AB  - Respiratory manifestations in Horton's disease are uncommon. We report the case
      of 63 year-old man with Horton disease diagnosed 2 months before, who was
      hospitalised for fever, deterioration in general health, cough and hemoptysis.
      Chest X-ray showed an infiltrate in the right upper lobe and bilateral cystic
      opacities predominant on basal suggesting bronchectasis who was confirmed
      secondary in CT-scan. Even though cortico sensible clinical manifestations and
      radiologic infiltrate were previously described in Horton's disease, association
      with bronchectasis was never been reported in literature and her etio pathogenic
      mechanism must be clarified.

PMID- 15453037
TI  - [Endometrial stromal nodule: a case report].
AB  - The endometrial stromal nodule is the rarest of the endometrial stromal tumours.
      It is a benign tumour composed of well-differentiated endometrial stromal cells
      arranged as a well-circumscribed nodule with smooth, non invasive margins. We
      describe a case of uterine stromal nodule occurring in a 45-year-old woman with
      history of menometrorrhagia in which case ultrasonography conclude to a
      leiomyoma. Epidemiology, pathologic aspects, differential diagnosis, treatment
      and prognosis are reviewed.

PMID- 15453038
TI  - [Multicentric extrahepatic bile ducts carcinoma. Clinical presentation,
      pathologic features and management].
AB  - Extrahepatic bile ducts carcinoma (EHBC) arises usually in the upper third of the
      biliary tract. They are rarely multicentric associated or not to a gallbladder
      carcinoma. We report the case of a 53 years man operated for a head pancreas.
      Laparatomy revealed a tumour of the middle common bile duct extending to the
      cystic duct. Histologically it was a multicentric carcinoma of variable types
      occurring in several sites of the biliary tract. Patient had undergone a simple
      resection without any complications 9 months later. Although EHBC are
      morphologically similar to those of the gallbladder, their risk factors,
      epidemiology and treatment are different. Prognosis depends on proximal
      involvement of perihilar bile ducts which makes the treatment only palliative.

PMID- 15453039
TI  - [Fatal miliary tuberculosis following treatment with Infliximab].
AB  - We report the first Tunisian case of miliary tuberculosis in a patient who
      received Infliximab for Crohn's disease with uretrorectal and ano-perineal
      fistula developed 4 weeks after the start of treatment. We suggest that diagnosis
      of latent tuberculosis infection is important before treatment with Infliximab is
      initiated and that antituberculous medication must be prescribed immediately in
      case of occurrence of unexplained fever after treatment with Infliximab.

PMID- 15453040
TI  - [Diagnostic and prognostic values of troponins in acute coronary syndromes].
AB  - Coronary disease is a frequent clinical entity which, in some cases, makes a
      difficult diagnostic problem. However, the very big revolution realised these
      last decades in both diagnostics and therapeutics, improved management of these
      patients. Troponins which are specific and sensitive biomarkers of myocardial
      damage were evaluated in several domains, especially in acute coronary diseases.
      We purpose to clarify diagnostic and prognostic place of these markers in acute
      coronary disease in order to optimize their clinical use.

PMID- 15453041
TI  - [Molecular study of Fanconi anemia in Tunisia].
AB  - Fanconi anemia (FA) is an autosomal recessive rare disease characterized by
      progressive pancytopenia, congenital malformations and predisposition to acute
      myeloid leukemia. Fanconi anemia is genetically heterogeneous, with at least
      eight complementation groups of FA (FAA to FAD2). In order to characterize the
      molecular defects underlying FA in Tunisia, fourty-one families were genotyped
      with microsatellite markers linked to known FA gene. Haplotype analysis and
      homozygosity mapping showed that 92% of these families belong to FAA group. We
      demonstrated the effectiveness of the molecular analysis for a better selection
      of bone marrow graft donor and for the evaluation of chimerism after bone marrow
      transplantation. This study also allows genetic counselling for FA family
      members.

PMID- 15453042
TI  - [Accidental caustic ingestion in Tunisian child. Study of 330 cases].
AB  - We studied retrospectively 330 cases of caustic product ingestion at the child
      collected in the pediatric department of Sousse (CHU Sahloul and CHU Farhat
      Hached) during eight years (1993-2000). It is about 194 boys and 136 girls (sex
      ratio to 1.42/1) aged of 4 months at 14 years (middle age at 3 years and 5
      months). Concerned products are dominated by the water of bleach (55.7%) dilute
      essentially (49%), caustic soda (27.9%), diluent of painting (8.5%), potash
      (2.7%) and the acidic products (2.2%). Endoscopy showed oeso-gastric lesions in
      89% of cases: oesophagitis stage I (73.5%), stage IIa (11%), stage IIb (4%),
      stage III (11.2%) and an inflammatory stenose case of straightaway. The
      associated gastric lesions have been found in 15.1% of the cases. The recovery
      was the rule for all patient presenting a benign oesophagitis. The 46 cases of
      severe oesophogitis have been treated according two protocols: --A group (n=1 ),
      treated by parenteral food with treatment by antibiotics (1993-1994). --B group
      (n=35), treated by high dose of corticosteroids (Methyl-prednisolone) aiming to
      warn esophageal stenosis (1995-2000). Three patients of the A group and five of
      the B group developed stenosis with statistically meaningful difference (p=0.44).
      Among these eight patients, six required oesophagoplasty and two had a good
      evolution after esophageal dilation.

PMID- 15453043
TI  - [HbA1c in the monitoring of type 1 diabetic patients].
AB  - We conducted this study to determine quality of glycemic control in patients with
      type 1 diabetes, based on evaluation of mean HbA1c. We enrolled 125 patients with
      type 1 diabetes who were hospitalized during the period from December 1998 to
      December 2001. Glycemic control was evaluated on mean of HbA1c in 82 patients and
      on mean of fasting glycemia values in 43 patients. Mean HbA1c was 9.9%. Mean of
      plasma fasting glycemia was 11 mmol/l. 22% of patients were perfectly or good
      controlled (HbA1c < or = 7% or HbA1c 7-7.5%). 12% had a moderate control (HbA1c
      7.5 et 9%) and finally 66% of patients had a worse control (HbA1c > 9%). There
      was an excellent correlation between HbA1c and mean fasting glycemic values (p =
      0.00028). Most of patients had unsatifactory control. We stressed on the absolute
      necessity of intensified insulin therapy and self-monitoring blood glucose.

PMID- 15453044
TI  - [Breech presentation: vaginal delivery or planned caesarean section?].
AB  - Breech delivery is a high risk situation because of its numerous dystocies. The
      most serious is the last head retention. The authors realized a retrospective
      study concerning 347 patients who had given birth to a newborn child in breech
      presentation during a period of 4 years. RESULTS: The vaginal delivery was
      associated in a significant way to an excess of obstetric traumatisms (5.5%)
      versus caesarean section (0.5%) and this even after strict selection of vaginal
      delivery's conditions (P = 0.00453). The rate of the newborn child having Apgar's
      score < 7 in 5 min was higher in case of vaginal delivery (17.39%) than caesarean
      section's birth (3.48%). Corrected neonatal mortality is higher in the group of
      vaginal delivery than caesarean section's group (34% versus 0.49%, P = 0.02553).
      There is no significant difference of maternal morbidity between caesarean
      section and vaginal delivery group (P = 4.65). Vaginal delivery is associated to
      an excess of morbidity and neonatal mortality even after strict selection of the
      candidates of the vaginal delivery.

PMID- 15453045
TI  - [Seasonal depressive disorder: a controlled study in Tunisian psychiatric
      sample].
AB  - Seasonal affective disorder is considered as a clinical subtype of major
      depression. The criteria for seasonal pattern has been recently described in the
      international classification of mental disorders. The aim of this study was to
      compare the clinical characteristics of patients with major depression and with a
      seasonal and a non seasonal pattern. The study was conducted at the psychiatric
      ward at Monastir university hospital. 16 inpatients with major depression and
      seasonal pattern, diagnosed with DSM-IV criteria, were matched in age, sex and
      diagnostic sub-type to 32 inpatients with non seasonal mood disorders. Clinical
      symptoms and short term course during the most recent depressive episode were
      obtained. The onset of the depression with seasonal pattern was frequently in
      winter. It was marked by significantly higher rates of anxiety. The patients with
      seasonal depression had significantly higher rates of dysphoria, atypical
      vegetative symptomatology and lower rates of psychotic characteristics and
      suicidal thoughts. No differences were found as to the psychiatric family
      histories or the age at the first depressive episode. This study could focus of
      the novel psychiatric entity and may lead to the development of the genetic and
      neurobiologic research related to seasonal affective disorder.

PMID- 15453046
TI  - [For a better promotion of the breast-feeding].
AB  - OBJECTIVE: Breast feeding has many advantages. Our objective is to determine
      influential factors on duration of exclusive breast feeding until 6 months of age
      and total breast feeding until 2 years. METHODS: A retrospective transversal
      study was made on 271 mothers of children aged between 2 and 5 years. The
      objective of study was to determinate factors which influence duration of
      exclusive and total breastfeeding. Epi-info was used to size and to analyse
      results, odds ratio and confiding intervals were calculated. Logistic regression
      method was also used. RESULTS AND COMMENTS: Duration of exclusive breastfeeding
      was longer when mother instruction was less than higher school (3.4 months versus
      2.9 months, p < 0.01), if there were not any maternal complications on
      breastfeeding period (4.3 months versus 3.1 months, p < 0.001). Duration of total
      breast feeding was longer when cow milk was introduced later and child sucking
      was important (more than 6 times a day). There was no correlation between weight
      and length of children and duration of breastfeeding. CONCLUSION: We recommend
      promotion of breastfeeding.

PMID- 15453047
TI  - [Common bile duct injuries during laparoscopic cholecystectomy].
AB  - Laparoscopic cholecystecmy is the preferred method for removing the Gall bladder.
      The most frequent intra-operative complications are by for related to the biliary
      tract: wounds, section. From September 1995 to August 2001, the authors have
      realized 1570 cases of laparoscopic cholecystectomy. There were 3 lesions of the
      common bile duct. Most of those complications are directly proportional to the
      operators experience. Their prevention depends on a perfect technics,
      understanding of the mechanisms and no hesitation in converting to conventional
      laparotomy whenever difficulties are encountered.

PMID- 15453048
TI  - [Gaucher's disease uncovered late].
AB  - Gaucher's disease is an uncommon inborn recessive autosomal disease, due to a
      deficient activity of the lysosomal enzyme beta glucocerebrosidase. This disease
      is usually diagnosed in the first or second decade of life with the arising of
      bone pains, splenomegaly and hemorragic manifestations due to thrombocytopenia.
      When the enlarged spleen is not evident, or after splenectomy, patients may be
      mis-identified as having Gaucher's disease. We present here two cases of elderly
      patients aged 70 and 46 years respectively, in whom the disease was a surprising
      finding of bone marrow examination, during check up for pancytopenia.

PMID- 15453049
TI  - [Multiple lymphomatous polyposis of the gastrointestinal tract: a Tunisian case].
AB  - Multiple lymphomatous polyposis is a distinctive primary gastrointestinal
      lymphoma which endoscopical, histopathological et immunophenotypical
      characteristics are well known. This lymphoma is rare and its prognosis is bad
      because of frequency of stage IV patients. We report the case of a 75-year-old
      male patient with multiple lymphomatous polyposis affecting the rectum, the colon
      and the stomach associated with an involvement of lymphadenopathies, bone marrow
      and liver. Treatment by chemotherapy was ineffective and patient dead after 3
      sessions of CEOP protocol.

PMID- 15453050
TI  - [Indications and results of vitrectomy in Terson syndrome].
AB  - Terson syndrome or vitreal hemorrhage associated with subdural hemorrhage is a
      rare condition. The goal of our work through a retrospective series of 3 cases (4
      eyes) is to study clinical characteristics as well as adequate moment of surgery.
      All our patients had unilateral or bilateral visual impairement secondary to
      cerebral lesion. Ophtalmologic exam showed an intravitreal hemorrhage. Two of our
      patients were operated by vitrectomy, the third case had a spontaneous resorption
      of intravitreal hemorrhage and no surgery was performed. Functional prognosis
      depends on neuro-ophtalmologic sequellas. Ophtalmic exam is essential in cerebral
      hemorrhage. For intravitreal hemorrhage spontaneous resorption is frequent and
      vitrectomy must be delayed.

PMID- 15453051
TI  - [Abscess of obturator internal muscle].
AB  - The abscess of obturator internal muscle is a rare disorder. The literature
      states only sporadic cases. Because of its rarity, the diagnosis is often late.
      Indeed, the presence of functional disability of the lower limb associated to a
      made septic syndrome evoke in the first of all, arthritis of the hip. We bring
      back (report) an observation illustrating the difficulties and the delay
      diagnosis of an abscess of the obturator internal muscle. It is about a ten year
      old girl having consulted for a septic syndrome with functional disability of the
      hip. The patient having been treated (handled) at the beginning for a cold of the
      hip. Secondarily she was operated for septic arthritis of the hip. The surgical
      investigation showed it self negative. It is only to the pelvien scanner realized
      after ten days of hospitalization that the diagnostic of abscess was reserved.
      The evolution has been favourable after surgical drainage and antibiotherapie.

PMID- 15453052
TI  - Acute cholangitis caused by intra-biliary rupture of pancreatic hydatid cyst.
AB  - A case of intra-biliary rupture of pancreatic hydatid cyst is presented. The site
      of the cyst in the pancreatic head, cholangitis, the advanced age of patient,
      previous history of cholecystectomy, liver hydatidosis and gastrectomy for ulcer
      disease, led to diagnostic and therapeutic difficulties. As in some cases of
      intra-biliary rupture of the liver hydatid cyst, surgical treatment of this
      pancreatic hydatid cyst included evacuation of cystic contents through
      choledocotomy and biliary-enteric anastomosis with uneventful postoperative
      course.

PMID- 15453053
TI  - [Epidemiologic features of myocardial infarction in young patients].
AB  - Acute myocardial infarction (AMI) in persons under the age of 45 years is
      uncommon. To determine the clinical features in young patients presenting with
      AMI, we include 38 patients with mean age 35 years who survive from myocardial
      infarction. This disease is almost associated with cardiovascular risk factors,
      the most common of which are tobacco abuse (90%) and diabetes (20%). The coronary
      arteries are most often normal (40%) or single vessel (33%). In hospital
      complications are the same as in the older adult but the prognosis seems to be
      better.

PMID- 15453054
TI  - Social work practice with people with disabilities: are we doing enough?

PMID- 15453055
TI  - Factors associated with self-worth in young people with physical disabilities.
AB  - Having a positive sense of self is associated with success for children and
      adults, with and without disabilities. This article reports on a cross-sectional
      study examining the correlates of global self-worth for 85 young people (ages
      eight to 23) with spina bifida (a condition present at birth) or spinal cord
      injury (an acquired condition). Significant correlations were found between
      perceptions of self-worth and age, perceived social support of close friends, and
      perceived social support from parents. Regression analysis revealed that
      perceived social support from parents was a stronger predictor of self-worth than
      gender, age, or diagnosis (onset of disability). Implications of this study for
      social work practice are discussed.

PMID- 15453056
TI  - Personal assistance providers' mistreatment of disabled adults.
AB  - This article describes a survey of 84 adults with disabilities who received
      personal assistance with activities of daily living from family members, informal
      providers, or agency personnel. Results showed that 30 percent reported
      mistreatment from their primary provider, and 61 percent reported mistreatment by
      another provider. Verbal abuse, physical abuse, and theft or extortion were the
      most common forms of mistreatment by primary providers. Verbal abuse, neglect,
      poor care, and theft were the most common forms of mistreatment by other
      providers. Adults with lower incomes were the most likely to experience
      mistreatment. Male providers were more likely to mistreat, as were providers who
      were inexperienced and who provided more than 50 hours of care per week.

PMID- 15453057
TI  - Medicaid managed care, substance abuse treatment, and people with disabilities:
      review of the literature.
AB  - Most states enroll individuals with disabilities who receive Supplemental
      Security Income (SSI) in Medicaid managed care plans. The impact of managed care
      on these individuals, especially those with substance abuse disorders, is not
      well understood. A review of the literature related to substance abuse,
      disability, and Medicaid managed care suggests that substance abuse is a serious
      issue for individuals with disabilities. More research is needed to determine how
      the substance abuse treatment needs of individuals with disabilities can be met
      through Medicaid managed care. The authors identified topics for a research
      agenda on the needs of individuals with disabilities who also experience co
      occurring substance abuse disorders. Implications for social work policy and
      practice are discussed.

PMID- 15453058
TI  - Counseling, support, and advocacy for clients who stutter.
AB  - Fluency disorders are communicative disabilities that can lead to psychosocial
      and emotional issues. The most prevalent of these disorders is stuttering. People
      who stutter may cope with stigmatization and discrimination throughout their
      lives as a result of misconceptions and misinformation about the disability's
      etiology and manifestations. Mental health professionals have contributed to
      these negative experiences by their lack of knowledge about stuttering. This
      article provides information on the physical, psychological, and social causal
      factors and implications of fluency disorders, so that social workers can engage
      in ethical practice to alleviate the mental anguish of their clients who stutter
      and enable them to reach their full potential. An advocacy role with other
      professionals, such as educators and speech-language pathologists, is described.

PMID- 15453059
TI  - Living with paraplegia: tensions and contradictions.
AB  - Although it is well established that paraplegia results in dramatic lifestyle
      changes, little is understood about living in the community with paraplegia,
      especially from the perspective of the person with paraplegia. To develop insight
      into this experience, in-depth, personal interviews were conducted with seven
      individuals with paraplegia who had been living back in the community for less
      than two years. Qualitative analysis of their transcribed interviews suggests
      that the transitional process revolved around their struggle to reposition
      themselves in a holististic way that reflects the injury while moving beyond it.
      Four interrelated challenges textured the experience: maintaining an identity
      beyond the medical; contending with the stigma of difference; addressing the
      invisible work of day-to-day living; and balancing independence and dependence.
      Implications for practice are discussed.

PMID- 15453060
TI  - Home health care utilization: a review of the research for social work.
AB  - The author reviewed the literature to identify the variables associated with home
      health care utilization using the Andersen-Newman model as a framework for
      analysis. Sixty-four studies published between 1985 and 2000 were identified
      through PUBMED, Sociofile, and PsycINFO databases. Home health care was defined
      as in-home skilled nursing, homemaker, mobile meals, home health aide, physical
      therapy, occupational therapy, or social work services. The review indicates that
      the client most likely to use home health care is elderly, has a high number of
      ADL/IADL impairments, lives alone, has a low level of informal support, and has
      Medicaid coverage. In the presence of informal support or when care recipients
      live with others, the initiation of formal services may be delayed until physical
      impairment of the care recipient is severe or caregiver burden is high.
      Implications for social work practice and research are discussed.

PMID- 15453061
TI  - A multidimensional assessment of children with chronic physical conditions.

PMID- 15453062
TI  - The compression of morbidity: implications for social work.

PMID- 15453063
TI  - Mentoring at every level. Mentoring others--and being mentored--enhances growth
      at every career stage.

PMID- 15453065
TI  - Revenue cycle acceleration: implementing electronic attachment of claims
      documents.

PMID- 15453064
TI  - The do's of IT strategic planning.

PMID- 15453066
TI  - CEO/CNO relationships: survey findings.

PMID- 15453067
TI  - Beyond HIPAA: ethics in the e-health arena. Ethical guidelines help ensure that
      credible health information appears on the Internet.

PMID- 15453068
TI  - Choosing an IT vendor.

PMID- 15453069
TI  - Maximizing physician recruitment programs.

PMID- 15453070
TI  - Developing patient-based marketing strategies.

PMID- 15453071
TI  - The real value of governance reform.

PMID- 15453072
TI  - Raising awareness. ACHE affiliate-led hospitals participate in cover the
      uninsured week.
AB  - ACHE affiliate-led hospitals participate in Cover the Uninsured Week.

PMID- 15453073
TI  - Understanding pay-for-performance programs.

PMID- 15453074
TI  - Using power and authority. Effective use of power is critical to your success,
      regardless of your position.

PMID- 15453075
TI  - Attracting healthcare's higher-ups. How can your chapter encourage senior-level
      executive participation?

PMID- 15453076
TI  - Picture archiving and communication systems.
AB  - Picture archiving and communication systems (PACS) are highly versatile data
      storage and retrieval systems that facilitate the transfer of digital images and
      patient data throughout a healthcare enterprise. Typically, they process images
      from diagnostic imaging modalities and are interfaced to radiology information
      systems (RISs) and hospital information systems (HISs) to improve overall
      workflow. For this Evaluation, we tested six PACS from six suppliers. Ideally, a
      PACS should allow the healthcare facility to achieve a fully automated workflow,
      in which patient image data is shared seamlessly from one system to another
      within a single electronic medical record (EMR). Although our testing found that
      this ideal has not yet been completely realized, many of the evaluated systems
      have taken significant steps in that direction. This Evaluation was limited to
      radiology PACS; however, more and more facilities are considering single PACS
      solutions to cover the needs of all their imaging departments.

PMID- 15453077
TI  - Pediatric defibrillation and AEDs.

PMID- 15453078
TI  - Hazard report. Patient injury or death could result from improper use of U.S.
      Surgical helical tacks.

PMID- 15453079
TI  - Hazard report. Ensuring sufficient disinfectant uptake during automated
      disinfection for hemodialysis machines.

PMID- 15453080
TI  - Hazard report. Inspection can prevent handle failures on Datascope intra-aortic
      balloon pumps.

PMID- 15453081
TI  - Factors affecting the resolution of surgical video systems.

PMID- 15453082
TI  - Measuring community preferences for public mental health services: pilot test of
      a mail survey method.
AB  - This study tested the feasibility of a simple mail survey approach to measuring
      community preferences for mental health services. A 38 item survey detected
      statistically significant differences in preferences for four central goals,
      finding that community members most value Focus on the Severely Mentally Ill,
      followed by Community Safety and Environment, Service Quality and Original
      Community Mental Health Goals. Some procedural problems were encountered that
      reduced the response rates, however, the study yielded information that suggests
      improved procedures for future surveys. Simple mail surveys appear to offer a
      potentially affordable, efficient way to assess community service priorities.

PMID- 15453083
TI  - Stigmatizing attitudes about mental illness and allocation of resources to mental
      health services.
AB  - This study tests a social psychological model (Skitka & Tetlock, 1992). Journal
      of Experimental Social Psychology, 28, 491-522; [1993]. Journal of Personality &
      Social Psychology, 65, 1205-1223 stating that policy maker decisions regarding
      the allocation of resources to mental health services are influenced by their
      attitudes towards people with mental illness and treatment efficacy. Fifty four
      individuals participated in a larger study of education about mental health
      stigma. Participants completed various measures of resource allocation
      preferences for mandated treatment and rehabilitation services, attributions
      about people with mental illness, and factors that influence allocation
      preferences including perceived treatment efficacy. Results showed significant
      attitudinal correlates with resource allocation preferences for mandated
      treatment, but no correlates to rehabilitation services. In particular, people
      who pity people with mental illness as well as those that endorse coercive and
      segregated treatments, were more likely to rate resource allocation to mandated
      care as important. Perceived treatment efficacy was also positively associated
      with resource allocation preferences for mandated treatment. A separate
      behavioral measure that involved donating money to NAMI was found to be inversely
      associated with blaming people for their mental illness and not being willing to
      help them. Implications of these findings on strategies that seek to increase
      resources for mental health programs are discussed.

PMID- 15453084
TI  - Differences in the indicators of depressive symptoms among a community sample of
      African-American and Caucasian older adults.
AB  - Depression among older adults is a major public health concern in the U.S. Yet,
      time and again this condition goes undiagnosed, or attributed to other causes.
      Despite being treatable, few individuals older than age 65 are treated for this
      disorder. Using a community sample of 404 African-American and Caucasian older
      adults, the aim of this study was to identify the sources of racial group
      variance in self-reports of depressive symptoms. Descriptive and multivariate
      analyses reveal no racial/ethnic differences in the mean level of depressive
      symptoms, but differences in the correlates of self-reported depression, as well
      as differences in the distribution of individual indicators of depressive
      symptoms.

PMID- 15453085
TI  - Impact of multi-agency employment services on employment rates.
AB  - Adults with severe and persistent mental illness who received employment services
      through mental health and/or vocational rehabilitation programs had higher
      employment rates than individuals who did not receive any employment services.
      Individuals who received services from both programs had significantly higher
      employment rates than individuals who received services from only one program.
      Results indicate that employment services had a greater relative effect on older
      clients and clients with a schizophrenia diagnosis than on other individuals.
      This state-wide study relied exclusively on analysis of
      administrative/operational databases that provide the employment rates for both
      recipients of vocational services and other clients.

PMID- 15453086
TI  - Utility of the behavioral model in predicting service utilization by individuals
      suffering from severe mental illness and homelessness.
AB  - This study compared the effectiveness of the behavioral model to predict two
      service utilization variables: case manager visits and total services used.
      Nearly 4000 individuals who were homeless and suffered from severe mental illness
      provided data for the study. Enabling variables explained more variance of both
      service utilization variables than predisposing or need variables. Social support
      from professionals was the strongest predictor for both service utilization
      variables.

PMID- 15453087
TI  - Utilization of psychiatric services integrated with primary care by persons of
      color with HIV in the inner city.
AB  - We identify the psychiatric diagnoses and utilization patterns of HIV-positive
      persons of color who received culturally responsive mental health services
      integrated into a community medical clinic. Ninety-three patients were referred
      and 86% (n = 80) appeared for at least one encounter. Hispanics, compared with
      African-Americans, and HIV patients, compared with AIDS patients, were more
      likely to receive psychotropic prescriptions. Patients with six or more visits
      were defined as high utilizers: they comprised 27.5% of the patients but used
      67.3% of the services. Development of a broader range of psychiatric
      interventions that address diagnoses, utilization, and psychotropics will better
      meet these patients' needs.

PMID- 15453088
TI  - Assessing psychiatric patients for violence.
AB  - Managing violent patients is a dilemma that every clinician faces. This article
      reviews the current literature and assesses the evidence on the management of
      violent patients in the clinical setting. Risk factors (dispositional,
      historical, contextual and clinical) and early warning signs of violence will be
      outlined. Understanding these issues will facilitate the short-term prediction
      and prevention of violence in clinical settings. Interventions have been
      categorized for use according to the urgency of the situation. This degree of
      urgency has been designated as either potential, imminent or emergent violence.
      Special considerations that may alter the management of violence will be
      delineated. Specifically, we will highlight issues related to gender, age and
      mental retardation. Aspects of professional training in regards to the management
      of the violent patient will be underscored as well. Finally, the review of the
      literature has led to a decision tree that can inform the reader in the evidence
      based management of the violent patient. This decision tree is offered to the
      busy practitioner as a practical clinical tool for using evidence based practices
      in managing violent patients.

PMID- 15453089
TI  - Cyclooxygenase-2 (COX-2) in inflammatory and degenerative brain diseases.
AB  - Cyclooxygenase (COX) catalyses the first committed step in the synthesis of
      prostanoids, a large family of arachidonic acid metabolites comprising
      prostaglandins, prostacyclin, and thromboxanes, and is a major target of non
      steroidal anti-inflammatory drugs (NSAIDs). COX exists as constitutive and
      inducible isoforms. COX-2 is the inducible isoform, rapidly expressed in several
      cell types in response to growth factors, cytokines, and pro-inflammatory
      molecules. Since its discovery in the early 1990s, COX-2 has emerged as a major
      player in inflammatory reactions in peripheral tissues. By extension, COX-2
      expression in brain has been associated with pro-inflammatory activities, thought
      to be instrumental in neurodegenerative processes of several acute and chronic
      diseases. However, 2 major aspects should be borne in mind. First, in the central
      nervous system, COX-2 is expressed under normal conditions and contributes to
      fundamental brain functions, such as synaptic activity, memory consolidation, and
      functional hyperemia. Second, "neuroinflammation" is a much more controlled
      reaction than inflammation in peripheral tissues, and in many cases is triggered
      and sustained by activation of resident cells, particularly microglia. In spite
      of the intense research of the last decade, the evidence of a direct role of COX
      2 in neurodegenerative events is still controversial. This article will review
      new data in this area, focusing on some major human neurological diseases, such
      as multiple sclerosis, amyotrophic lateral sclerosis, Parkinson disease,
      Creutzfeldt-Jakob disease, and Alzheimer disease. Furthermore, the emerging role
      of COX-2 in behavioral and cognitive functions will be discussed.

PMID- 15453090
TI  - Staging of argyrophilic grains: an age-associated tauopathy.
AB  - We have reported that the ambient gyrus is the site with the greatest
      accumulation of argyrophilic grains (AGs) and that the degeneration of the
      ambient gyrus is responsible for dementia with grains. Here we analyzed 1,405
      serial autopsy cases from 2 hospitals and detected AGs only in cases older than
      56 years of age. The distribution of AGs followed a stereotypic regional pattern.
      Thus, we propose the following staging paradigm: stage I: AGs restricted to the
      ambient gyrus and its vicinity; stage II: AGs more apparent in the anterior and
      posterior medial temporal lobe, including the temporal pole, as well as the
      subiculum and entorhinal cortex; and stage III: abundant AGs in the septum,
      insular cortex, and anterior cingulate gyrus, accompanying spongy degeneration of
      the ambient gyrus. Sixty-three of 65 (96.9%) argyrophilic grain stage III cases
      without other dementing pathology were classified as 0.5 or higher in the
      clinical dementia rating. Forty-seven of 50 dementia with grains cases (94%) were
      stage III and 3 were stage II. No association with apoE genotyping was detected.
      Our study further confirms that dementia with grains is an age-associated
      tauopathy with relatively uniform distribution and may independently contribute
      to cognitive decline in the elderly.

PMID- 15453091
TI  - Long-term denervation in humans causes degeneration of both contractile and
      excitation-contraction coupling apparatus, which is reversible by functional
      electrical stimulation (FES): a role for myofiber regeneration?
AB  - Over the last 30 years there has been considerable interest in the use of
      functional electrical stimulation (FES) to restore movement to the limbs of
      paralyzed patients. Spinal cord injury causes a rapid loss in both muscle mass
      and contractile force. The atrophy is especially severe when the injury involves
      lower motoneurons because many months after spinal cord injury, atrophy is
      complicated by fibrosis and fat substitution. In this study we describe the
      effects of long-term lower motoneuron denervation of human muscle and present the
      structural results of muscle trained using FES. By means of an antibody for
      embryonic myosin, we demonstrate that many regenerative events continue to
      spontaneously occur in human long-term denervated and degenerated muscle (DDM).
      In addition, using electron microscopy, we describe i) the overall structure of
      fibers and myofibrils in long-term denervated and degenerated muscle, including
      the effects of FES, and ii) the structure and localization of calcium release
      units, or triads; the structures reputed to activate muscle contraction during
      excitation-contraction coupling (ECC). Both apparatus undergo disarrangement and
      re-organization following long-term denervation and FES, respectively. The poor
      excitability of human long-term DDM fibers, which extends to the first periods of
      FES training, may be explained in terms of the spatial disorder of the ECC
      apparatus. Its disorganization and re-organization following long-term
      denervation and FES, respectively, may play a key role in the parallel
      disarrangement and re-organization of the myofibrils that characterize
      denervation and FES training. The present structural studies demonstrate that the
      protocol used during FES training is effective in reverting long-term denervation
      atrophy and dystrophy. The mean fiber diameter in FES biopsies is 42.2 +/- 14.8
      SD (p < 0.0001 vs DDM 14.9 +/- 6.0 SD); the mean percentile of myofiber area of
      the biopsy is 94.3 +/- 5.7 SD (p < 0.0001 vs DDM 25.7 +/- 23.7 SD); the mean
      percentile fat area is 2.1 +/- 2.4 SD (p < 0.001 vs DDM 12.8 +/- 12.1 SD); and
      the mean percentile connective tissue area is 3.6 +/- 4.6 SD (p < 0.001 vs DDM
      61.6 +/- 20.1 SD). In DDM biopsies more than 50% of myofibers have diameter
      smaller than 10 microm, while the FES-trained subjects have more that 50% of
      myofibers larger than 30 microm. The recovery of muscle mass seems to be the
      result of both a size increase of the surviving fibers and the regeneration of
      new myofibers.

PMID- 15453092
TI  - Axon mediated interneuron migration.
AB  - Mammalian forebrain development requires extensive cell migration for cells to
      reach their appropriate location in the adult brain. Defects in this migration
      result in human malformations and neurologic deficits. Thus, understanding the
      mechanisms underlying normal cell migration during development is essential to
      understanding the pathogenesis of human malformations. Radial glia are known to
      support radial cell migration, while axons have been proposed as substrate for
      some non-radially migrating cells. Herein we have directly tested the hypothesis
      that axons can support non-radial cell migration. One population of cells known
      to migrate non-radially is the inhibitory interneurons that move from the
      ganglionic eminence to the cerebral cortex. We first show that early born
      GABAergic cells colocalize with TAG-1-positive (TAG-1+) axons, while later born
      cells colocalize with intermediate weight neurofilament-positive, TAG-1-negative
      (TAG-1-) processes, suggesting temporal differences in substrate specificities.
      We next developed an in vitro assay that allows us to observe cell migration on
      axons in culture. Using this assay we find that early born medial ganglionic
      eminence-derived interneurons migrate preferentially on TAG-1+ axons, while later
      born cells only migrate on neurofilament-positive/TAG-1- processes. These data
      provide the first direct evidence that ganglionic eminence cells migrate on axons
      and that there is an age-dependent substrate preference. Furthermore, the assay
      developed and characterized herein provides a robust method to further study the
      molecular substrates and guidance cues of axonophilic cell migration in neural
      development.

PMID- 15453093
TI  - A role for interferon-gamma in focal cerebral ischemia in mice.
AB  - The pro-inflammatory cytokine interferon-gamma (IFNgamma) has traditionally been
      associated with inflammatory CNS disease and more recently with ischemia-induced
      pathology. Using a murine model of focal cerebral ischemia, we found no evidence
      for induction of IFNgamma mRNA after permanent middle cerebral artery occlusion.
      In addition, we found that mice deficient in IFNgamma or IFNgamma receptors
      developed neocortical infarcts similar in size to those in wild type. In
      contrast, MBP promoter-IFNgamma-transgenic mice consistently developed
      significantly larger infarcts than non-transgenic mice. Because IFNgamma is a
      potent activator of microglia-macrophages, we investigated the involvement of
      microglial-macrophage-derived TNF in the larger infarcts. Numbers of TNF mRNA
      expressing microglia-macrophages and levels of TNF mRNA and TNF in IFNgamma
      transgenic and non-transgenic mice were similar. Furthermore, the ischemic brain
      damage in IFN-gamma-transgenic mice was unaffected by recombinant soluble TNF
      receptor I. Taken together, the data argues against a role for IFNgamma in
      cerebral ischemia under normal conditions. However, when present, IFNgamma
      significantly exacerbates ischemia-induced brain damage by mechanisms that appear
      to be independent of TNF or synergistic neurotoxic interactions of IFNgamma and
      TNF Irrespective of the mechanism(s) involved, this enhancing effect of IFNgamma
      on ischemia-induced neurotoxicity may need to be considered in diseases where
      immune IFNgamma is involved, such as multiple sclerosis.

PMID- 15453094
TI  - Arachidonylethanolamide induces apoptosis of human glioma cells through vanilloid
      receptor-1.
AB  - The anti-tumor properties of cannabinoids have recently been evidenced, mainly
      with delta9-tetrahydrocannabinol (THC). However, the clinical application of this
      drug is limited by possible undesirable side effects due to a broad expression of
      cannabinoid receptors (CB1 and CB2). An attractive field of research therefore is
      to identify molecules with more selective tumor targeting. This is particularly
      important for malignant gliomas, considering their poor prognosis and their
      location in the brain. Here we investigated whether the most potent endogenous
      cannabinoid, arachidonylethanolamide (AEA), could be a candidate. We observed
      that AEA induced apoptosis in long-term and recently established glioma cell
      lines via aberrantly expressed vanilloid receptor-1 (VR1). In contrast with their
      role in THC-mediated death, both CB1 and CB2 partially protected glioma against
      AEA-induced apoptosis. These data show that the selective targeting of VR1 by AEA
      or more stable analogues is an attractive research area for the treatment of
      glioma.

PMID- 15453095
TI  - Activated microglia initiate motor neuron injury by a nitric oxide and glutamate
      mediated mechanism.
AB  - Recent studies suggest that motor neuron (MN) death may be non-cell autonomous,
      with cell injury mediated by interactions involving non-neuronal cells, such as
      microglia and astrocytes. To help define these interactions, we used primary MN
      cultures to investigate the effects of microglia activated by lipopolysaccharide
      or IgG immune complexes from patients with amyotrophic lateral sclerosis.
      Following activation, microglia induced MN injury, which was prevented by a
      microglial iNOS inhibitor as well as by catalase or glutathione. Glutamate was
      also required since inhibition of the MN AMPA/kainate receptor by CNQX prevented
      the toxic effects of activated microglia. Peroxynitrite and glutamate were
      synergistic in producing MN injury. Their toxic effects were also blocked by CNQX
      and prevented by calcium removal from the media. The addition of astrocytes to
      cocultures of MN and activated microglia prevented MN injury by removing
      glutamate from the media. The protective effects could be reversed by inhibiting
      astrocytic glutamate transport with dihydrokainic acid or pretreating astrocytes
      with H2O2. Astrocytic glutamate uptake was also decreased by activated microglia
      or by added peroxynitrite. These data suggest that free radicals released from
      activated microglia may initiate MN injury by increasing the susceptibility of
      the MN AMPA/kainate receptor to the toxic effects of glutamate.

PMID- 15453096
TI  - Role of Ang1 and its interaction with VEGF-A in astrocytomas.
AB  - Angiopoietins (Ang1 and Ang2) modulate the activity of the endothelial cell (EC)
      specific receptor tyrosine kinase Tie2, which together with vascular endothelial
      growth factor (VEGF-A) and its EC-specific receptors, VEGFR1 and VEGFR2, regulate
      normal physiological vessel development. The functional role of angiopoietins in
      tumor angiogenesis, in particular astrocytoma angiogenesis, remains unclear. In
      this study, we focus on the specific contribution of Ang1 to the vascular growth
      of glioblastoma multiforme (GBM) and its interactive role with VEGF-A.
      Subcutaneous and intracranial GBM xenografts were generated using 3 established
      astrocytoma cell lines (U87, U373, and U343) that were transfected to stably over
      express Ang1. GBM xenografts were also generated to express low levels of VEGF-A
      and high Angl. We found that Ang1 increases the vascular growth of both
      subcutaneous and intracranial xenografts of GBM by approximately 3-fold. However,
      the increased vascular growth was only seen in xenografts with concurrent VEGF-A
      elevation, since decreasing VEGF-A expression resulted in a loss of the pro
      angiogenic growth advantage seen with Ang1. Collectively, our data suggest that
      Ang1 regulates GBM vascularity in a VEGF-A dependent manner, synergizing the
      initial pro-angiogenic response that is triggered by VEGF-A and promoting the
      vascular growth of GBM.

PMID- 15453098
TI  - Teens, drugs, and sadness. Is a combo of pills and talking the best remedy for
      depression?

PMID- 15453097
TI  - Developmental lag in superoxide dismutases relative to other antioxidant enzymes
      in premyelinated human telencephalic white matter.
AB  - Periventricular leukomalacia (PVL) involves free radical injury to developing
      oligodendrocytes (OLs), resulting from ischemia/reperfusion, particularly between
      24 and 32 gestational weeks. Using immunocytochemistry and Western blots, we
      tested the hypothesis that this vulnerability to free radical toxicity results,
      in part, from developmental lack of superoxide dismutases (SOD)-1 and -2,
      catalase, and glutathione peroxidase (GPx) in the telencephalic white matter of
      the human fetus. During the period of greatest PVL risk and through term (> or =
      37 weeks), expression of both SODs (for conversion of O2- to H2O2) significantly
      lagged behind that of catalase and GPx (for breakdown of H2O2), which, in
      contrast, superseded adult levels by 30 gestational weeks. Our data indicate that
      a developmental "mismatch" in the sequential antioxidant enzyme cascade likely
      contributes to the vulnerability to free radical toxicity of the immature
      cerebral white matter, which is "unprepared" for the transition from a hypoxic
      intrauterine to an oxygen-rich postnatal environment. All enzymes, localized to
      astrocytes and OLs, had higher-than-adult expression at 2 to 5 postnatal months
      (peak of myelin sheath synthesis), suggesting an adaptive mechanism to protect
      against lipid peroxidation during myelin sheath (lipid) synthesis. The previously
      unrecognized dissociation between the expression of the SODs and that of catalase
      and GPx in the fetal period has potential implications for future antioxidant
      therapy in PVL.

PMID- 15453099
TI  - Gambling: the hidden addiction.

PMID- 15453100
TI  - The road less travelled: moving from distribution to determinants in the study of
      gambling epidemiology.
AB  - This article reviews the current status of gambling epidemiology studies and
      suggests that it is time to move from general population-prevalence research
      toward the investigation of risk and protective factors that influence the onset
      of gambling disorders. The study of incidence among vulnerable and resilient
      populations is a road yet to be taken. In this review, we briefly introduce the
      history of the field and thoroughly review the epidemiologic research on
      disordered gambling before providing a critical assessment of the current
      diagnostic tools. Overall, the extant research shows that disordered gambling is
      a relatively stable phenomenon throughout the world. Given that certain segments
      of the population (for example, adolescents and substance users) have elevated
      prevalence rates, we suggest focusing future prevalence studies on groups with
      apparently increased vulnerability. Moreover, we suggest that, for the field of
      gambling studies to progress, researchers need to take the road less travelled
      and examine more carefully the onset and determinants of disordered gambling.
      That said, given the problems with the current diagnostic screens, investigators
      need to refine their theoretical concepts and the epidemiologic tools used to
      examine them before the field can travel down this new road.

PMID- 15453101
TI  - Assessing and treating problem gambling: empirical status and promising trends.
AB  - OBJECTIVE: Ways to clinically assess and treat problem gambling evolve as our
      knowledge about this disorder increases. This paper summarizes current knowledge
      about treating problem gambling and describes developments in the assessment,
      psychology, and biology of problem gambling that may be important for treatment.
      METHODS: We reviewed recent published literature reporting advances in the
      assessment, psychology, and biology of problem gambling. We retained for review
      only controlled clinical trials in which subjects were randomized to either
      psychological or pharmacologic treatment. RESULTS: Although several gambling
      treatments were found to be efficacious, support for any specific treatment
      modality is still limited. Cognitive-behavioural treatments were most effective.
      Although diagnostic assessment has improved, there are still very few measures of
      gambling-related variables. The contribution to gambling of sex, concurrent
      psychiatric disorders, cognitive distortions, and impulsivity has been described.
      Evidence implicating decision-making areas of the cortex and disturbances in
      serotonin and dopamine functioning has been reviewed. Available evidence for a
      genetic contribution to problem gambling is weak. CONCLUSIONS: Improvements in
      the methodology of gambling-treatment research were discussed to advance the
      clinical approach to this disorder. Developments in the area of assessment,
      psychology, and biology of gambling should inform clinical approaches to a
      greater degree than they currently do. We identified the need to study different
      types of gambling separately, rather than combining them, as an important goal.

PMID- 15453102
TI  - Preventing postpartum depression part II: A critical review of nonbiological
      interventions.
AB  - OBJECTIVE: To critically review the literature to determine the current state of
      scientific knowledge concerning the prevention of postpartum depression (PPD)
      from a nonbiological perspective. METHODS: Databases searched for this review
      include Medline, PubMed, Cinahl, PsycINFO, Embase, ProQuest, the Cochrane
      Library, and the World Health Organization Reproductive Health Library. Studies
      selected were peer-reviewed English-language articles published between January
      1, 1966, and December 31, 2003. Criteria used to evaluate the interventions were
      derived from the standardized methodology developed by the Canadian Task Force on
      Preventive Health Care. RESULTS: Twenty-nine studies that met criteria were
      examined. These included studies evaluating interpersonal psychotherapy,
      cognitive-behavioural therapy, psychological debriefing, antenatal classes,
      intrapartum support, supportive interactions, continuity of care, antenatal
      identification and notification, early postpartum follow-up, flexible postpartum
      care, educational strategies, and relaxation with guided imagery. CONCLUSIONS:
      While this review demonstrates that no specific approach can be strongly
      recommended for clinical practice, many explicit research implications have been
      highlighted. To further address PPD as a public health problem, it is critical to
      include ethnically and socioeconomically diverse women in research efforts
      examining the differences among depression symptoms, intervention response rates,
      and health service use.

PMID- 15453103
TI  - Continuity of care in mental health services: toward clarifying the construct.
AB  - OBJECTIVE: To clarify "continuity of care" (COC), a construct associated with the
      delivery of services for persons suffering from severe and persistent mental
      illness (SPMI), with attention to the service recipient's perception of COC.
      METHOD: The study involved a systematic appraisal of the literature on COC,
      supplemented by interviews with 36 SPMI patients and their families. Statements
      highlighting attributes of COC were extracted from both sources. RESULTS:
      Comments by patients and families corresponded to descriptions of COC in the
      mental health literature. Attribute classifications by independent teams of
      judges showed good consistency. The following 4 attribute domains of the COC
      construct were identified: service delivery, accessibility, relationship base,
      and individualized care. CONCLUSIONS: Service recipients' perceptions of COC
      overlapped with representations of the construct in the mental health literature.
      The qualitative inquiry resulted in a draft, 47-item, self-report questionnaire
      for use in studies of interventions designed to facilitate COC.

PMID- 15453104
TI  - The boundary between borderline personality disorder and bipolar disorder:
      current concepts and challenges.
AB  - OBJECTIVE: The boundary between borderline personality disorder (BPD) and bipolar
      disorder (BD) is a controversial subject. Clinically, it can be difficult to
      diagnose patients who present with both affective instability and impulsivity.
      This paper reviews concepts and challenges related to the overlap of these
      disorders. METHODS: A Medline search was conducted, using the key words
      borderline personality disorder, bipolar disorder, affective disorder, and
      personality disorder. Reference lists from articles generated were also used.
      Publications from the last 20 years were considered. RESULTS: Studies demonstrate
      a greater cooccurrence between these 2 disorders than between BPD and other Axis
      I disorders or between BD and other Axis II disorders. Some authors suggest that
      many patients diagnosed with BPD are better described as having BD, that the
      bipolar classification is too narrow, or that BPD should be considered a variant
      of affective disorders. Others present evidence supporting BPD as a valid
      construct. Hypotheses about the relation between the 2 disorders and suggestions
      for clinical practice are offered. CONCLUSIONS: There appears to be sufficient
      evidence to consider BPD to be a valid diagnosis. Both disorders apply to
      heterogeneous populations, and their characteristics require further
      clarification. In diagnostically challenging situations, careful consideration of
      a patient's longitudinal history is essential. Future research will be important
      to ensure that our diagnostic classifications reflect clinically useful entities.

PMID- 15453105
TI  - Selective serotonin reuptake inhibitor and venlafaxine use in children and
      adolescents with major depressive disorder: a systematic review of published
      randomized controlled trials.
AB  - OBJECTIVE: This review critiques published randomized placebo-controlled trials
      pertaining to the efficacy and safety of selective serotonin reuptake inhibitors
      (SSRIs) and venlafaxine in the treatment of major depressive disorder in children
      and adolescents. METHOD: Medline was searched for articles meeting defined
      inclusion criteria. The following key terms were used: depressive disorders,
      antidepressive agents, fluoxetine, paroxetine, sertraline, citalopram,
      fluvoxamine, venlafaxine, child, and adolescent. RESULTS: Six articles met
      inclusion criteria. Only 2 studies claim efficacy by significant results in
      primary outcomes; both have since been contested in further analysis. Not one
      study adequately examines safety, particularly with respect to whether a link
      exists between antidepressant use and induction of suicidal ideation or attempts.
      CONCLUSION: Published studies on SSRI or venlafaxine use in children and
      adolescents are inconclusive with respect to safety and efficacy, owing to
      inappropriate claims of efficacy, lack of improvement in global functioning
      scores, nonstandardized data collection regarding adverse effects, exclusion of
      suicidal subjects in the recruitment process, grouping of children and
      adolescents together, small sample sizes, conflict of interest posed by
      pharmaceutical company sponsorship, and publishing bias. Future investigators
      should consider these factors when developing study designs.

PMID- 15453106
TI  - Twenty-year course of schizophrenia: the Madras Longitudinal Study.
AB  - OBJECTIVE: To follow up 90 first-episode schizophrenia patients after 20 years
      and to study the course of symptomatology, work, social functioning, and pattern
      of illness during this period. METHODS: The Present State Examination and the
      Psychiatric and Personal History Schedule were administered at fixed points
      during follow-up. The measures adopted to ensure a good follow-up rate (67%)
      after 20 years under adverse conditions are described. RESULTS: Complete data
      were obtained from 61 subjects; 16 had died, and 13 could not be traced. After 20
      years, 5 patients had recovered completely, and another 5 were continuously ill.
      Most of the cohort had multiple relapses with or without complete remission
      between them. The Global Assessment of Functioning Scale showed that symptoms and
      social functioning in this sample approximated results from developing countries
      and were much better than those of developed nations. There were not many sex
      differences. Marriage and occupational rates were higher than those observed in
      many published reports. CONCLUSIONS: This is one of the few long-term follow-up
      studies from the developing world. It reveals a pattern of course and functioning
      distinctly better than that found in many such studies from the developed
      nations.

PMID- 15453107
TI  - Attention-deficit hyperactivity disorder in a sample of Omani schoolboys.

PMID- 15453108
TI  - Effective use of olanzapine for obsessive-compulsive symptoms in a patient with
      bipolar disorder.

PMID- 15453109
TI  - Monoamine oxidase inhibitors and subarachnoid hemorrhage.

PMID- 15453110
TI  - Beyond haloperidol: teaching emergency medicine residents to manage acute
      agitation and aggression in the emergency department.

PMID- 15453111
TI  - Hypothalamic-pituitary-adrenal function and preventing major depressive episodes.

PMID- 15453112
TI  - A Romanian adoptee's journey from latency age to adolescence.

PMID- 15453113
TI  - [Non-alcoholic liver steatorrhea secondary to clozapine].

PMID- 15453114
TI  - Re: A case-control study on psychological symptoms in sleep apnea-hypopnea
      syndrome.

PMID- 15453115
TI  - [Fever, coughing and/or wheezing in young children: consider the possibility of
      foreign body aspiration].
AB  - Three children, 2 girls aged 1.5 and 3 years and a 2-year-old boy, experienced
      coughing, wheezing and/or fever for several days or weeks. The first girl was
      treated for asthma, the other two children for pneumonia. Because the symptoms
      persisted in all three children after treatment was started, the diagnosis of
      foreign body aspiration was suggested and confirmed by bronchoscopy. The foreign
      body was removed during the bronchoscopy and in the boy, a mucosal lesion in the
      piriform fossa was sutured. Thereafter, all the children recovered completely. In
      children with persistent coughing, wheezing or fever despite treatment for
      pneumonia or asthma and in absence of a characteristic acute incident, foreign
      body aspiration should be considered.

PMID- 15453116
TI  - [Amphotericin B: the end of an era].
AB  - For 45 years, amphotericin B has been the drug of choice for the treatment of
      invasive mycoses. Because of its severe toxicity, lipid-associated formulations
      of amphotericin B have been developed. Although comparative trials are scarce,
      there appears to be no convincing advantage of these new formulations in terms of
      efficacy. The lipid-associated amphotericins are significantly less nephrotoxic
      than conventional amphotericin B, although there are major differences in the
      infusion-related toxicity of the various lipid-associated preparations. The
      current armamentarium of azoles and echinocandins for the treatment of invasive
      mycoses has only left a very minor role for both conventional and lipid
      associated amphotericin B in the treatment of a few specific, rare mycoses.

PMID- 15453117
TI  - [Long-acting insulin analogs: progressing slowly].
AB  - In the last few years short-acting insulin analogs have become increasingly
      popular. Their introduction has unmasked serious deficiencies in the capacity of
      isophane insulin to provide a stable basal insulinaemia. The long-acting insulin
      analogs, insulin glargine and insulin detemir, have been developed as
      alternatives to isophane insulin. Insulin glargine has a long duration of action
      and has demonstrated its usefulness in diabetes type 2, specifically a lower
      incidence of (nocturnal) hypoglycaemia compared to isophane insulin, in clinical
      practice. Insulin detemir has a very low variability in absorption and also seems
      to reduce the risk of nocturnal hypoglycaemia in diabetes type 1. More studies
      are, however, needed. Because of the higher costs of these novel insulins, the
      decision to switch a patient from isophane insulin to an insulin analog has to be
      made on an individual basis.

PMID- 15453118
TI  - [Chemotherapy for metastased non-small cell lung cancer].
AB  - Only a select group of patients with metastased non-small cell lung cancer are
      eligible for treatment with chemotherapy. The standard treatment for patients
      with a good performance score, and possibly also for those with physical
      limitations as a consequence of the disease, is chemotherapy consisting of
      cisplatin or carboplatin in combination with a third-generation cytotoxic agent
      together with maximum supportive care. The optimal duration of this chemotherapy
      treatment is at least 3 to 4 cures, less in the case of disease progression. For
      older patients (> 70 years) with a good performance score, chemotherapy with
      maximum supportive care is the standard treatment. However, which form of
      chemotherapy should be given is not yet clear. Symptomatic improvement is
      important for improving the quality of life. For patients with tumour relapse or
      disease progression after first-line chemotherapy who still have a good
      performance score, the standard treatment is once again chemotherapy with maximum
      supportive care, as this improves the chance of survival and quality of life, and
      is possibly cost effective.

PMID- 15453119
TI  - [Long acting insulin analogs: possibly more stable glucose regulation].
AB  - A better diabetes regulation seems possible, with the aid of the recently
      available insulin analogs than with isophane insulin, for patients with diabetes
      mellitus type 1 or 2. The glycaemic regulation can be improved and/or the chances
      of hypoglycaemia can be reduced by reduced variability in the resorption of
      (insulin glargine) or by binding to the serum albumin (insulin detemir). With
      poor regulation it seems possible to bring about a substantial HbA1c reduction
      without an increase in hypoglycaemic incidents, and with reasonable to good
      regulation to achieve a reduction of the number of hypoglycaemias whilst HbA1c
      remains the same.

PMID- 15453120
TI  - [New developments in antifungal therapy: fluconazole, itraconazole, voriconazole,
      caspofungin].
AB  - The azole antifungal voriconazole and the echinocandin caspofungin have recently
      become available for the treatment of invasive mycoses. Fluconazole remains the
      drug of choice for candidemia, except for infections with one of the resistent
      species such as Candida krusei and some strains of Candida glabrata. In these
      cases, as well as in patients who cannot tolerate azoles in connection with side
      effects or drug interactions, caspofungin is an attractive alternative.
      Voriconazole has become the drug of choice for severe invasive aspergillosis.
      Itraconazole is a good alternative for milder and chronic forms of aspergillosis.
      The use of conventional amphotericin B will be limited by the availability of the
      new drugs. In view of their high costs, the lipid-bound forms of amphotericin B
      will usually be given only as salvage therapy in case of failure, in patients who
      are unable to tolerate either conventional amphotericin or one of the newer
      agents, and for the treatment of zygomycosis.

PMID- 15453121
TI  - [Diagnostic image (203). A woman with hypercalcaemia and osteolytic lesions
      caused by primary hyperparathyroidism].
AB  - A 76-year-old woman presented with hypercalcaemia and osteolytic lesions, caused
      by primary hyperparathyroidism.

PMID- 15453122
TI  - [Thyrotoxic crisis in a patient with Graves' disease].
AB  - A 33-year-old man presented with diarrhoea, dyspnoea, palpitations, fever and
      shock. One year and a half before admission, Graves'-hyperthyroidism had been
      diagnosed, for which he was treated with thiamazole and levothyroxine as block
      replacement therapy. A diagnosis of thyrotoxic crisis, precipitated by lack of
      compliance with antithyroid drug therapy and possibly an underlying infection,
      was made. Euthyroidism was achieved with propylthiouracil, potassium iodide,
      corticosteroids and propranolol. However, the propylthiouracil had to be stopped
      due to agranulocytosis, after which hyperthyroidism recurred. An emergency
      thyroidectomy was then performed; the patient recovered completely. Thyrotoxic
      crisis is a rare, potentially life-threatening disease in patients with
      underlying un(der)treated hyperthyroidism. It is characterised by fever,
      tachycardia, and neurological and gastrointestinal symptoms.

PMID- 15453123
TI  - [Salmonella osteomyelitis in a child with sickle cell disease].
AB  - In an eight-months-old girl with sickle cell disease, osteomyelitis due to
      Salmonella arizona was diagnosed. Osteomyelitis caused by Salmonella species is
      rare in children. However, in patients with sickle cell disease it is the
      responsible pathogen in more than 50% of cases. The differentiation between, the
      much more common, bone crisis and osteomyelitis in sickle cell patients is often
      difficult. Ultrasound and bone marrow scans may be helpful. It is not known why
      Salmonella causes osteomyelitis in patients with sickle cell disease. What is
      clear, however, is that osteomyelitis usually occurs shortly after a preceding
      bone crisis. Empiric antibiotic treatment of osteomyelitis in patients with
      sickle cell disease should include coverage for Salmonella species. The patient
      described was initially treated with cefuroxime and gentamicin, but once the
      culture result was known this was switched to amoxicillin. As new infection foci
      later occurred in the bone the treatment was switched to ceftriaxone i.v. which
      was later substituted by ciprofloxacin orally. With this all of the skeletal
      abnormalities were fully corrected.

PMID- 15453124
TI  - [Non-respiratory cyanosis in the newborn].

PMID- 15453125
TI  - [Diagnostic image (192). A man with intermittent gross hematuria].

PMID- 15453126
TI  - [Clinical reasoning and decision making in practice. A depressive foreign woman
      with symptoms of malaise].

PMID- 15453127
TI  - [Genetic research with stored human tissue: a coding procedure with optimal use
      of information and protection of privacy].

PMID- 15453128
TI  - [Are patients with mechanical heart valves allowed to have a MRI?].

PMID- 15453129
TI  - [Continuous military-and-medical education in modern conditions].

PMID- 15453130
TI  - [On evaluation of treatment-and-diagnostic work conducted in the troop link of
      military service].

PMID- 15453131
TI  - [Expert work during technogenic extreme situations (Report II)].
AB  - The article is devoted to the organizational principles of work of expert
      institutions and its subdivisions with reference to technogenic catastrophes with
      mass victims. The problems of interactions of representatives from different
      structures and departments made busy with the work at the place of event are
      discussed in terms of forensic medicine. Special attention is paid to the
      problems of expert institution readiness for work under conditions of extreme
      situations depending on the medical-and-tactical characteristics of damage focus.

PMID- 15453132
TI  - [The specialized medical aid improvement for treating the wounded and patients of
      microsurgical profile].
AB  - On the base of restorative surgery Center of Vishnevsky Central Military Clinical
      Hospital the department was developed. The main direction of its work is the
      treatment of sequelae of extremity gunshot injuries accompanied with defects of
      soft tissues, bony structures, tendinous-and-ligamentous apparatus, neurovascular
      fascicles, etc. During the period from January 1990 to December 2003 387
      casualties and patients (in whom 423 surgical interventions were performed) were
      investigated and treated. It was possible to decrease the incidence of
      complications that influenced on fighting pathology final outcome in 8.5 times,
      to reduce the treatment period in 1.5 times. The number of cases of patient
      dismiss underwent the microsurgical interventions was twice less. These values
      were compared with those obtained in the wounded underwent the conventional
      plastic operations ("Filatov pedicle", "Italian" plasty, autodermoplasty, etc.)
      at the stage of rendering the qualified surgical aid during the period of
      military operation in Afghanistan (1979-1989).

PMID- 15453133
TI  - [Metabolic syndrome: modern approaches to diagnosis and treatment principles].

PMID- 15453134
TI  - [Microbial eczema: clinical picture, pathogenesis and treatment principles].

PMID- 15453135
TI  - [The specific features of malaria clinical course debut in servicemen arrived in
      tropics from non-malariogenic regions].
AB  - The specific features of initial period of vivax and tropical malaria were
      defined with the help of clinical-and-laboratory methods in two groups of
      servicemen (70 persons in each group) differed by the period of stay in tropics.
      For comparison 30 similar patients, the tropics inhabitants, were investigated.
      In local inhabitants the course of all forms of malaria was rather mild with
      development of disease characteristic paroxysms in most of them. The reverse
      correlation of disease severity and period of servicemen' stay in tropics was
      revealed. For both forms of malaria the migrants compared with local inhabitants
      had the prodromal period and initial fever without typical paroxysms. The
      following debuts of malaria were revealed in servicemen: the frequent (influenza
      like, arthralgia-like, gastrointestinal, bronchopneumonic, typhoid-like) and the
      rare (abdominal and painful, cerebral: meningeal and comatose, dysentery-like,
      tuberculosis-like, hemorrhagic). The shown features of malaria initial period in
      servicemen caused difficulties in its early diagnosis.

PMID- 15453136
TI  - [Express-assessment of body functional state conducted in submariners].

PMID- 15453137
TI  - [The military-and-medical education in Samara is 50 years].

PMID- 15453138
TI  - [Medical care quality improvement in multipurpose hospital].

PMID- 15453139
TI  - Organizational wisdom.
AB  - In recent years, much theoretical and empirical attention has focused on wisdom
      as a psychological construct. The development of wisdom is viewed as a positive
      aspect of aging, but also has a complement to more traditionally-studied domains
      of intelligence. Two studies, involving a total of 327 adults, examined how our
      understanding of the construct might be furthered by its application into
      specific, problematic contexts, and by having its utility assessed. This
      involved: 1) development of an instrument that related the elements of wisdom to
      the context of work organizations; 2) identification of the primary ways in which
      wisdom contributes to well-being in work organizations; and 3) identification of
      types of organizations (organizational cultures) most likely to need and value
      wise persons of influence in their midst. Results suggest that wisdom is of
      greatest consequence when it fills an important gap in what is offered by the
      organization's (or society's) formal structure. Where the culture has developed
      more formal institutions, structure, and principles to guide its activities and
      ensure fairness in how people are treated, there may be less need for informal
      sources of organizational wisdom.

PMID- 15453140
TI  - Socialization or social structure: investigating predictors of attitudes toward
      filial responsibility among Chinese urban youth from one- and multiple-child
      families.
AB  - This study explores the influence of familial and social factors on the maturing
      cohort of China's one-child generation students' attitudes toward filial
      responsibilities. Based on survey data collected in 1997 and 1998 among 777
      Chinese young adults, this research found that family economic conditions had a
      significant impact on young adults' attitudes; higher family income was
      positively related to respondents' willingness toward accepting filial
      responsibility; higher educational levels, though positively related to
      respondents' attitudes toward xiao, were negatively related to their commitment
      to parent care when they foresaw job and care conflicts. Family socialization was
      not found to enhance young adults' attitudes toward filial responsibility.
      Sharing the same household with grandparents and having dependent grandparents in
      the family were negatively associated with respondents' sense of obligation for
      parental care. Further, only children born after the one-child policy
      implementation scored lower than other children in their willingness to provide
      parental care when they foresaw job and care conflicts. The author argues that
      social structure, rather than socialization, plays an increasingly important role
      in shaping one-child generation students' attitudes toward filial responsibility
      in China, and will continue to do so in the future.

PMID- 15453141
TI  - Individual differences in the effects of disease and disability on depressive
      symptoms: the role of age and subjective health.
AB  - Each person is affected by disease and disability differently. This study
      examined the role of age and subjective perception of health in determining the
      links of depressive symptoms with disease and disability among older adults of
      different ages. The hypothesized effects of age and subjective health were tested
      using 252 older adults divided into three age groups (i.e., 60s, 80s, and 100s).
      Two major findings emerged. First, individuals with advanced old age had higher
      levels of health problems, as expected. However, their perceptions of health and
      depressive symptoms were less affected by disability when compared to the younger
      old. Second, regardless of age, the effects of disease and disability on
      depressive symptoms were mediated through subjective health. Findings suggest age
      differences in the consequences of health problems, and the importance of
      subjective perception to bridge physical and mental health. Issues such as age
      differences within older populations, the resilience of centenarians, and the
      intervening roles of subjective health are further discussed.

PMID- 15453142
TI  - Aging and categorization: could relevant pieces of information reduce older
      persons' inhibitory deficit?
AB  - The goal of this study was to reduce the inhibitory deficit on the elderly by
      creating "optimizing conditions" in a categorization task. It was hypothesized
      that increasing the number of relevant pieces of information would reduce the
      difficulty associated with processing irrelevant information on a categorization
      task, since the number of relevant solutions to solve the problem would increase,
      while the total number of pieces of information to be processed would remain the
      same. This hypothesis was tested on 27 young adults and 30 elderly people using a
      task requiring the matching of a stimulus figure to one of the two response
      figures having one or more attributes in common with the stimulus. In line with
      previous findings, the results indicated an age-related inhibitory decline.
      However, consistent with the hypothesis, as the number of relevant attributes
      increased, the performance of elderly people improved and response times
      decreased, supporting the notion of latent cognitive resources.

PMID- 15453143
TI  - Longitudinal effects of social support on the health and functioning of older
      women with heart disease.
AB  - This study examined the effects of: 1) four dimensions of social support, 2) the
      number of close social ties, and 3) marital status on the physical and
      psychological health and functioning of 471 women aged 60 years and over with
      heart disease. Linear mixed models were used to assess the impact of each
      baseline social relations predictor on health outcomes at four-, 12-, and 18
      month follow-up intervals. A second set of models examined the association
      between change in support variables over time with concomitant change in health
      outcomes. Results indicated that baseline emotional/ informational support,
      positive social interaction, affectionate support, tangible support, number of
      close friends and relatives, and marital status all significantly predicted (p <
      .05) one or more health outcomes over time. Increases in positive social
      interaction and emotional support over time were significantly associated with
      concurrent improvement in all self-reported physical and psychological health
      outcomes. Interventions that enhance the availability of emotional/informational
      support and promote social interaction are needed for this population.

PMID- 15453144
TI  - [Hepatitis B (acute and chronic)].

PMID- 15453145
TI  - [Fibromyalgia and working ability--experience of a rheumatological appreciation
      center].
AB  - Fibromyalgia is a painful syndrome frequently leading to a rheumatological
      expertise. Between January 1998 and August 2003, 260 medical appraisals were
      carried out in the department. Forty-three people matched the fibromyalgia
      classification criteria proposed by the American College of Rheumatology. This
      number represents a twofold increase compared to the period ranging from 1968 to
      1997. One quarter were men. The group of people with fibromyalgia (Exp. FM+) was
      compared with a group of patients undergoing a similar evaluation without
      fibromyalgia (Exp. FM-), matched for age and sex. There were no differences
      concerning the demographic characteristics nor increase in obesity, heart rate or
      decreased blood pressure in the Exp. FM+ group. In people mentioning back pain,
      Waddell tests for a non organic origin of the pain tended to be more present in
      this group. There were no more triggering events, heavy labor workers or a
      decreased education level in the Exp. FM+ group. Fatigue, sadness, irritability
      and evocation of suicide were more frequently noted in the fibromyalgia group.
      People with work disablement higher than 50% were no more numerous in the Exp.
      FM+ group. Similarly, the working ability level in the last job or in an
      appropriated job was not decreased in the Exp. FM+ group. In this study,
      comparison between people with and without fibromyalgia yielded no great
      differences and working ability was regarded to be equivalent.

PMID- 15453146
TI  - [The role of interventional pain therapy in palliative care].
AB  - The effective treatment of severe pain requires a multimodal approach with a
      thorough knowledge of the pharmacological properties of the individual drugs. Non
      opioid analgesics are surprisingly effective and compare well to opioids. Due to
      the pain-induced changes in the spinal cord, the resulting tolerance and the
      specific effect of tumor mediators on the pain process, an effective treatment
      strategy requires in 10-30% of the tumor patients in the last weeks of their life
      an interventional approach to pain management. The common techniques involve
      neuroaxial delivery of local anaesthetics and opioids. There has been an abundant
      experience with these techniques in the perioperative setting. The indications
      are uncontrollable pain states and/or severe side effects of pain therapy
      including the cognitive deterioration with high dose opioids. The complications
      are mainly technical and are mostly due to catheter obstruction or disconnection.
      The increasing use of elastomeric pumps reduces the weight of the reservoir and
      allows the patient an easy adjustment of the flow rate.

PMID- 15453147
TI  - [Is GHB use in Switzerland on the rise?].

PMID- 15453148
TI  - [A 59-year old patient with herpes zoster V1-V2].

PMID- 15453149
TI  - [The fire bush (Hamelia) heats the bacteria].

PMID- 15453151
TI  - The politicization of medicine.

PMID- 15453150
TI  - [A better dying? Beginning of modern hospice movements and their historical
      provisions].

PMID- 15453152
TI  - Utility of MELD and Child-Turcotte-Pugh scores and the Canadian waitlisting
      algorithm in predicting short-term survival after liver transplant.
AB  - BACKGROUND: The Model for End-Stage Liver Disease (MELD) and Child-Turcotte-Pugh
      (CTP) scores are important predictors for survival after liver transplantation
      (LT). The objective of this study was to compare the utility of MELD and CTP
      scores with Canadian waitlisting algorithm in transplantation (CanWAIT) status
      for predicting 90-day survival after LT. METHODS: Retrospectively, we analyzed
      all 228 liver transplants performed in adults by the Atlantic Liver Transplant
      Program since 1985. These cases included combined transplants, retransplants and
      those after fulminant liver failure. MELD and CTP scores were calculated, and
      CanWAIT status and waiting time on the day of LT determined. We used c-statistic
      for 90-day outcome as the endpoint (survival), comparing areas under the receiver
      operating characteristic (ROC) curves for MELD and CTP scores and CanWAIT status.
      RESULTS: Mean (and standard deviation [SD]) MELD score was 18 (SD 12); CTP score,
      10 (SD 3); and waiting time, 97 (SD 132) days. At the time of LT, 54% were in
      CanWAIT status 1; 4% in 1T; 14% in 2; 11% in 3; 6% in 3F; 4% in 4; and 7% in
      status 4F. Overall 90-day survival was 80% (95% confidence interval [CI] 75%
      85%), exceeding the predicted survival by MELD scale with transplant of only 51%
      (CI 47%-55%). By c-statistic, CanWAIT is a clinically relevant predictor of 90
      day outcomes in LT. By multivariate regression analysis, only CanWAIT status and
      age were found to have independent associations for short-term outcomes after LT.
      INTERPRETATION: CanWAIT status stratifies LT patients better and predicts short
      term outcome more accurately than MELD or CTP scores, and so should not be
      replaced by MELD or CTP scores. This observation should be confirmed by a
      prospective and multicentre study in Canada.

PMID- 15453153
TI  - Introduction to the special theme issue on psychosocial issues in disasters and
      terrorism.

PMID- 15453154
TI  - Overview of the psychosocial impact of disasters.
AB  - The psychosocial sequelae can be intense and of long duration in the aftermath of
      natural and technological disasters, as well as terrorist attacks. Post-traumatic
      stress symptoms and full syndrome disorder, depression, anxiety, somatic
      complaints, and excessive alcohol use have been demonstrated consistently,
      particularly following large-scale disasters. This paper examines the
      psychological research conducted at various intervals after extensive natural
      disasters, the Three Mile Island and Chernobyl technological accidents, and
      recent terrorist events in the United States. Factors predictive of the emergence
      of emotional distress and psychological and physical problems following a
      disaster also are discussed.

PMID- 15453155
TI  - Psychological impact of disasters and terrorism on children and adolescents:
      experiences from Australia.
AB  - Recent acts of terrorism have emphasised the need for research to further
      establish not only the nature of the impact of disaster and terrorism on the
      population, but also further define methods of effective intervention. Those
      affected, and often overlooked, include children and adolescents, yet, our
      knowledge of the impact upon the younger members of our community is limited. The
      literature is evolving, and there are a small number of valuable studies that can
      inform a response to the mental health needs of this younger population. This
      article reviews some of the psychological impacts of disaster and terrorism upon
      children and adolescents, and considers both risk and protective factors. The
      importance of a developmental approach to children's understanding of disaster,
      particularly death and the nature of grief and loss are discussed as is the
      distinction between the phenomenology of bereavement and trauma. Family and
      community support are highlighted as protective factors, and a number of recent,
      valuable recommendations for intervention including psychological first aid and
      cognitive-behavioral therapy are described. Finally, the complex role of the
      media and the degree that children should be exposed to images of violence and
      disaster is considered. Disasters, whether they are natural or human-made always
      will be with us. It is necessary that a public-health approach that not only
      prepares for such scenarios, but responds by maximising the use of existing
      systems and agency linkages, is taken.

PMID- 15453156
TI  - When disaster strikes: responding to the needs of children.
AB  - When a disaster strikes, parents are quick to seek out the medical advice and
      reassurance of their primary care physician, pediatrician, or in the case of an
      emergency, an emergency department physician. As physicians often are the first
      line of responders following a disaster, it is important that they have a
      thorough understanding of children's responses to trauma and disaster and of
      recommended practices for screening and intervention. In collaboration with
      mental health professionals, the needs of children and families can be addressed.
      Policy-makers and systems of care hold great responsibility for resource
      allocation, and also are well-placed to understand the impact of trauma and
      disaster on children and children's unique needs in such situations.

PMID- 15453157
TI  - Minimizing casualties in biological and chemical threats (war and terrorism): the
      importance of information to the public in a prevention program.
AB  - The most effective means of defending against biological or chemical warfare,
      whether in war or as a result of terror, is the use of primary prevention. The
      main goal of such a prevention program is to minimize the human loss by reducing
      the number of casualties (fatalities, physical wounds, and psychological injury).
      A secondary objective is to prevent the widespread sense of helplessness in the
      general population. These two aims complement each other. The more the public is
      active in defending itself, rather than viewing itself as helpless, the lesser
      the expected number of casualties of any kind. In order to achieve these two
      goals, educating the civilian population about risk factors and pointing out
      appropriate defensive strategies is critical. In the absence of an effective
      prevention program and active participation by the public, there is a high risk
      for massive numbers of physical and psychological casualties. An essential
      ingredient of any preventive program, which ultimately may determine the success
      or failure of all other protective actions, is early, gradual dissemination of
      information and guidance to the public, so that citizens can become active
      participants in the program. The public needs to be given information concerning
      the nature of the threat and effective methods of coping with it, should an
      unconventional attack occur. Lack of such adaptive behavior (such as wearing
      protective gear) is likely to bring about vast numbers of physical and
      psychological casualties. These large numbers may burden the medical, political,
      and public safety systems beyond their ability to manage. Failure to provide
      reasonable prevention and effective interventions can lead to a destruction of
      the social and emotional fabric of individuals and the society. Furthermore,
      inadequate preparation, education, and communication can result in the
      development of damaging mistrust of the political and military leadership,
      disintegration of social and political structures, and perhaps, even risk the
      collapse of the democracy.

PMID- 15453158
TI  - The traumatic process: conceptualization and treatment.
AB  - Traumatic stress stems from a threat to an individual's or a group's very
      existence. The impact of the existential threat may be compounded by an inability
      to cope, which affects the perception of helplessness and loss of lawfulness. A
      model is proposed in which the traumatic process is conceptualized to develop
      through three stages: (1) alert; (2) impact; and (3) post-trauma. In this model,
      treatment of traumatic stress emphasizes the need to control and expand life, and
      to achieve lawfulness and meaningfulness. In the proposed model of treatment,
      there are essential differences at each of the stages of the traumatic process:
      (1) primary prevention at the stage of alert focuses on planning strategies for
      coping; (2) secondary prevention at the stage of impact is based on forward
      treatment and debriefing; and (3) tertiary treatment at the post-trauma stage
      attends to coping with internal chaos and arbitrariness.

PMID- 15453159
TI  - Integration of disaster mental health services with emergency medicine.
AB  - Despite limited resources, emergency medical settings will be called upon to play
      many roles in the context of disasters and terrorist attacks that are related to
      preparedness, surveillance, mental health services delivery, and staff care. Such
      settings are a central capture site for those individuals likely to be at highest
      risk for developing mental health and functional problems. Because much of the
      potential harm to survivors of disaster or terrorism (and their families) will be
      related to their mental health and role functioning, preparedness requires the
      active integration of behavioral health into emergency medicine in every
      component of disaster response. There are many challenges of doing this
      including: (1) finding ways to integrate activities of the medical care,
      emergency response, and public health systems; (2) determining whether an
      incident has actually occurred; (3) making differential diagnoses and managing
      other aspects of initial medical needs; and (4) coping with the risks associated
      with system overload and failure. Delivery of direct mental health care must
      include: (1) survivor and family education; (2) identification and referral of
      those requiring immediate care and follow-up; (3) group education and support
      services; and (4) individual counseling. In order for effective response to
      occur, the integration of psychosocial care into disaster response must occur
      prior to the disaster itself, and will depend on effective collaboration between
      medical and mental health care providers. At workplaces, emergency medical care
      centers must ensure that staff and their families are properly trained and
      supported with regard to their disaster functions and encouraged to develop
      personal/family disaster plans.

PMID- 15453160
TI  - Disaster and terrorism: Cognitive-Behavioral interventions.
AB  - The mental health effects of disaster and terrorism have moved to the forefront
      in the recent past following the events of 11 September 2001 in the United
      States. Although there has been a protracted history by mental health researchers
      and practitioners to study, understand, prevent, and treat mental health problems
      arising as a result of disasters and terrorism, there still is much to learn
      about the effects and treatment of trauma. Continued communication among disaster
      workers, first-response medical personnel, and mental health professionals is
      part of this process. This paper outlines current knowledge regarding the
      psychological effects of trauma and best cognitive-behavioral practices used to
      treat trauma reactions. More specifically, the information presented is a summary
      of Cognitive-Behavioral Therapy (CBT) interventions that are relevant for
      responding to and dealing with the aftermath of disasters.

PMID- 15453161
TI  - Acute psychological impact of disaster and large-scale tauma: limitations of
      traditional interventions and future practice recommendations.
AB  - Nearly everyone will experience emotional and psychological distress in the
      immediate aftermath of a disaster or other large-scale traumatic event. Although
      extremely upsetting and disruptive, the reaction is understood best as a human
      response to inordinate adversity, which in the majority of cases remits over time
      without formal intervention. Nevertheless, some people experience sustained
      difficulties. To prevent chronic post-traumatic difficulties, mental health
      professionals provide early interventions soon after traumatic exposure. These
      interventions typically take the form of single-session debriefings, which have
      been applied routinely following disasters. The research bearing on these
      traditional forms of early crisis interventions has shown that, although well
      received by victims, there is no empirical support for their continued use.
      However, promising evidence-based, early interventions have been developed, which
      are highlighted. Finally, traumatic bereavement and complicated grief in
      survivors of disasters, an area largely neglected in the field, is discussed.

PMID- 15453162
TI  - Vicarious traumatization: potential hazards and interventions for disaster and
      trauma workers.
AB  - Disaster and trauma workers often disregard their own reactions and needs when
      focusing on caring for those directly exposed to traumatic events. This article
      discusses the concept of vicarious traumatization, a form of post-traumatic
      stress response sometimes experienced by those who indirectly are exposed to
      traumatic events. It includes an examination of how vicarious trauma reactions
      are experienced across different professions, and suggestions on how to limit or
      prevent vicarious traumatization. The authors review self-care strategies as well
      as training and organizational considerations that may be beneficial for
      individuals and organizations to address.

PMID- 15453163
TI  - Disaster intervention: long-term psychosocial benefits in Armenia.
AB  - This paper describes a unique situation in which disaster intervention following
      a massive earthquake led to significant, uninterrupted, psychosocial benefits to
      the entire country, and an intervention program that continues to evolve. The
      mental health program initially provided service to the victims, and then,
      training to local professionals during which personnel simultaneously conducted
      clinical research. Members of the mental health team made a life-long commitment
      to the country, and continue their activities to expand its impact on public
      health policy. The difficult history and life circumstances of the Armenian
      people provided the opportunity for disaster interventions to have extensive
      psychosocial benefits.

PMID- 15453164
TI  - Preventing after-effects of disaster trauma: the information and support centre.
AB  - This paper describes the establishment and activities of the Information and
      Support Centres developed in Norway in the aftermath of large-scale accidents and
      disasters between 1980 and 1990. The function of these Centres is to provide
      rapid, authoritative information and psychosocial support services for the next
      of-kin of disaster victims, including the families of those missing. By gathering
      together those affected by a particular event, the Centres provide a setting in
      which individuals and families can support each other. The activities of the
      psychosocial team include triage for mental-health emergencies, orienting
      survivors to immediately available local services, communication with family,
      friends, and community, and other forms of psychological first aid. The
      psychosocial team also provides linkages to local health, clergy, and other local
      resources that are near to the family's home and could provide continued care if
      necessary.

PMID- 15453165
TI  - The challenges facing mental health programs for post-conflict and refugee
      communities.
AB  - The majority of refugees and communities exposed to warfare and oppression live
      in low-income countries with few resources or special skills. Yet,
      epidemiological studies have identified high levels of traumatic stress reactions
      in such populations. These stress reactions can be intensified by harsh policies
      aimed at deterring survivors from seeking refuge in technologically advanced
      societies. The scale of the problem of mass violence and displacement creates
      formidable challenges for mental health professionals in their efforts to develop
      practical frameworks for responding to the extensive needs of displaced persons.
      In this article, a model is proposed for low-income, post-conflict countries,
      based on a two-tiered formulation. At the eco-social level, mental health
      professionals can play a supportive, but not a lead, role in facilitating
      recovery of core adaptive systems that hasten natural recovery from stress for
      the majority of the population. Where small-scale, community mental health
      services are established, the emphasis should be on assisting persons and their
      families who are at greatest survival and adaptive risk. Training and promotion
      of local workers to assume leadership in such programs are essential. In
      technologically advanced societies in which refugees are in a minority, torture
      and trauma services can focus more specifically on traumatic stress reactions,
      acculturation, and resettlement. In a historical epoch in which displaced persons
      are facing particularly harsh treatment, there is a pressing need for consensus
      amongst mental health professionals in advocating for their needs.

PMID- 15453166
TI  - Using ethnographic methods in the selection of post-disaster, mental health
      interventions.
AB  - This paper describes a short, ethnographic study approach for understanding how
      people from non-Western cultures think about mental health and mental health
      problems, and the rationale for using such an approach in designing and
      implementing mental health interventions during and after disasters. It describes
      how the resulting data can contribute to interventions that are more acceptable
      to local people, and therefore, more effective and sustainable through improved
      community support.

PMID- 15453167
TI  - Ethnic differences in symptoms of post-traumatic stress after the Exxon Valdez
      oil spill.
AB  - INTRODUCTION: Previous studies have reported ethnic differences in the prevalence
      of post-traumatic stress disorder (PTSD), but the reasons for these differences
      remain unclear. HYPOTHESIS: Ethnic differences in the prevalence of PTSD may
      reflect ethnic differences in (1) exposure to traumatic events; (2) appraisal of
      such event as traumatic; and (3) culturally-determined responses to standardized
      diagnostic instruments, reflecting differences in cultural meanings associated
      with physical symptoms and idioms of distress. METHODS: Ethnic differences in
      risk factors and factor structures of PTSD symptoms were examined in 188 Alaskan
      Natives and 371 Euro-Americans exposed to the Exxon-Valdez oil spill in 1989.
      RESULTS: High levels of social disruption were associated with PTSD one year
      after the oil spill in both ethnic groups. However, low family support,
      participation in spill clean-up activities, and a decline in subsistence
      activities were significantly associated with PTSD in Alaskan Natives, but not in
      Euro-Americans. Factor analysis of the Diagnostic Interview Schedule PTSD
      subscale revealed five factors for both ethnic groups. However, the items
      comprising these factors were dissimilar. CONCLUSIONS: These results suggest that
      social disruption is sufficiently traumatic to be associated with symptoms of
      post-traumatic stress, but that a diagnosis of PTSD must take into consideration
      local interpretations of these symptoms.

PMID- 15453168
TI  - The San Diego East County school shootings: a qualitative study of community
      level post-traumatic stress.
AB  - INTRODUCTION: Within one month (March 2001), two separate incidents of school
      shootings occurred at two different high schools within the same school district
      in San Diego's East County. OBJECTIVE: To examine community-wide expressions of
      post-traumatic distress resulting from the shootings that may or may not fulfill
      DSM-IV criteria for post-traumatic stress disorder (PTSD), but which might
      interfere with treatment and the prevention of youth violence. METHODS: A
      qualitative study was undertaken using Rapid Assessment Procedures (RAP) in four
      East San Diego County communities over a six-month period following the two
      events. Semi-structured interviews were conducted with 85 community residents
      identified through a maximum variation sampling technique. Interview transcripts
      were analyzed by coding consensus, co-occurrence, and comparison, using text
      analysis software. RESULTS: Three community-wide patterns of response to the two
      events were identified: (1) 52.9% of respondents reported intrusive reminders of
      the trauma associated with intense media coverage and subsequent rumors, hoaxes,
      and threats of additional acts of school violence; (2) 44.7% reported efforts to
      avoid thoughts, feelings, conversations, or places (i.e., schools) associated
      with the events; negative assessment of media coverage; and belief that such
      events in general cannot be prevented; and (3) 30.6% reported anger, hyper
      vigilance, and other forms of increased arousal. Twenty-three (27.1%) respondents
      reported symptoms of fear, anxiety, depression, drug use, and psychosomatic
      symptoms in themselves or others. CONCLUSIONS: School shootings can precipitate
      symptoms of post-traumatic stress disorder at the community level. Such symptoms
      hinder the treatment of individuals with PTSD and the implementation of effective
      prevention strategies and programs.

PMID- 15453169
TI  - Risk factors for adolescent alcohol use following a natural disaster.
AB  - INTRODUCTION: On 29 March 1998, a series of category F-3 and F-4 tornadoes caused
      wide-spread destruction in four rural southern Minnesota counties in the United
      States. Extensive research has examined the impact of disaster exposure on
      adults' psychological functioning, including alcohol use. However, there has been
      little research on potential risk factors for adolescents' alcohol use following
      disaster exposure. HYPOTHESIS: It was hypothesized that demographic variables
      such as age and gender, prior drinking involvement, extent of prior trauma
      history, level of disaster exposure, and current disaster-related, post-traumatic
      stress disorder (PTSD) symptomatology would predict alcohol use among
      adolescents. METHODS: Six months following a natural disaster, survey data were
      collected from 256 adolescents assessing these factors. Risk factors for
      adolescents' alcohol use were identified using hierarchical, multiple regression
      and logistic regression analyses. RESULTS: Greater age, prior drinking
      involvement, and the extent of prior trauma history were significantly associated
      with higher levels of binge drinking. Prior trauma history and current levels of
      disaster-related PTSD symptomatology were significant risk factors for
      adolescents' report of increases in their alcohol consumption since the tornado.
      CONCLUSION: In general, the extent of trauma exposure was associated with greater
      binge drinking among adolescents. Similar to adults, post-traumatic stress
      symptoms experienced in the aftermath of a disaster can lead to increased alcohol
      consumption among adolescents.

PMID- 15453170
TI  - Health disparities affecting African American.

PMID- 15453171
TI  - ACU column 15.3 (August 2004).

PMID- 15453172
TI  - Structural violence and racial disparity in HIV transmission.
AB  - Among women of color in the United States, infection with the human
      immunodeficiency virus (HIV) is rising. Most of the research on this topic,
      however, has focused on individual-level risk factors, which do not fully explain
      racial or ethnic differences in infection rates. This article uses structural
      violence as a conceptual framework to examine ecological-level risk factors
      leading to disparate rates of heterosexually transmitted HIV among women of color
      in Syracuse, New York. Three ecological pathways to disproportionate infection
      are discussed: community rates of infection, concurrent partnerships, and
      increased vulnerability. The discussion of the pathways considers the following
      macro-level risk factors: disproportionate incarceration rates of African
      American men, residential segregation, gang turf, constraints on access to
      sexually transmitted disease services, an African American sex ratio in which
      women outnumber men, social norms stigmatizing homosexuality, and commercial
      sales of douching products. The authors argue that health care providers and
      policy analysts must address ecological-level risk factors for HIV transmission
      in underserved communities.

PMID- 15453173
TI  - Medical debt and consumer credit counseling services.

PMID- 15453174
TI  - Health risk and promotion behaviors in refugee populations.
AB  - Refugees resettling in the U.S. are generally low-income and underserved by
      health promotion interventions. To begin to address refugee health promotion
      issues, this study describes health behaviors of newly arrived (less than 90
      days) adult refugees in the U.S. The methods used were retrospective description
      of clients from one refugee health screening program. The sample consisted of
      adult refugees (n=591), men and women, from Cuba, Bosnia, Vietnam, Kosovo, Iran,
      Iraq, and other countries. Rates of overweight were highest among Bosnians and
      lowest among Vietnamese. Cubans reported the most physical activity and Kosovars
      the least. Rates of smoking were highest among Bosnians and lowest among Cubans.
      Older refugees were more overweight and reported less physical activity and more
      smoking than younger adults. In some cases, different refugee groups have similar
      health promotion needs, while in others needs differ. This baseline descriptive
      data supports calls for further health promotion research and interventions in
      refugee populations.

PMID- 15453175
TI  - Opportunities for outreach: Medicaid participation among children in Ohio.
AB  - This research seeks to determine individual and household differences between
      children who enrolled in Medicaid and the Children's Health Insurance Program
      (CHIP) and children who did not. In addition, the study investigates the specific
      reasons that families provided for not enrolling their children in Medicaid/CHIP.
      Data from the 1998 Ohio Family Health Survey were used to determine individual
      and household differences between children who were enrolled in Medicaid and CHIP
      and children who were not. Findings show that lower household income, parental
      unemployment, parental health insurance, and younger (child) age, were associated
      with greater participation in Medicaid/CHIP among eligible children in Ohio.
      Children in poorer health and those who resided in counties with higher levels of
      expenditures on outreach were also more likely to be enrolled. Findings from this
      study suggest a substantial need to increase awareness about program eligibility
      and to develop creative outreach strategies aimed at reaching nontraditional
      Medicaid families.

PMID- 15453176
TI  - Breast and cervical cancer screening among Mississippi Delta women.
AB  - The purpose of the study was to determine breast and cervical cancer screening
      among women living in the Mississippi Delta region. Using data from the
      Behavioral Risk Factor Surveillance System for 1999--2000, we determined the
      prevalence of mammography (women 40 years and older, n = 6,028) and Pap testing
      (women 18 years and older, n = 6,502) within the past 2 or 3 years, respectively.
      We examined predictors of testing and compared results with those for women
      living elsewhere in the United States. Among Delta women, 69.4% (95% confidence
      interval [CI] 67.9% to 70.9%) had a mammogram and 85.5% (95% CI 84.3% to 86.6%) a
      Pap test. Mammography prevalence was lower among black and white Delta women than
      among black and white women elsewhere. Pap testingwas lower among older (65 years
      and older) Delta women or women who did not visit a doctor within the past year
      than among their counterparts elsewhere. Additional interventions are needed to
      meet the goals of Healthy People 2010 for all women.

PMID- 15453177
TI  - Mammography rescreening among women of diverse ethnicities: patient, provider,
      and health care system factors.
AB  - This study identified patient, provider, and health care system factors that
      influenced mammography rescreening among non-insured, racial/ethnic minority
      women. Data were collected using a stratified-clustered random sample survey of
      1,050 women of five racial/ethnic groups (Latina, Chinese, Filipina, African
      American, and Caucasian) and 102 primary care clinical sites. Women received
      screening services through two no-cost screening programs in California. Chi
      square tests were used to assess bivariate associations and multiple logistic
      regressions were used to compute adjusted odds ratios and 95% confidence
      intervals. Mammography rescreening was associated with living in the United
      States longer; having higher education levels, better health care access, a
      history of breast problems, and favorable perceptions of mammography; obtaining
      regular Pap screening and hormone replacement therapy; having had better
      communication with clinicians; and attending clinics that conducted in-reach
      activities. This study suggests that simply removing financial barriers is not
      enough to improve mammography rescreening among underserved women.

PMID- 15453178
TI  - Availability of and access to medical services among HIV-infected inmates
      incarcerated in North Carolina county jails.
AB  - This study assessed human immunodeficiency virus (HIV)-related services in county
      jails and staff perceptions of HIV-infected inmates and their care. A statewide
      telephone questionnaire was administered to detention officers and health care
      workers providing medical services in North Carolina jails. Eighty-five percent
      of participating facilities employed one or more on-site medical personnel,
      including physicians (51%), physician assistants (14%), and nurses (71%). Only
      25% of jails tested more than one inmate for HIV per month. In 75% of jails,
      initial medical screening was performed in a common area. Officers administered
      medical screening forms at 93% of jails and distributed medications at 81%.
      Ninety-three percent of officers and 94% of medical staff agreed with this
      statement: "If an inmate is taking medications in jail, other inmates will know
      about it." Overall, our data indicate that few North Carolina jail inmates are
      tested for HIV. Greater protection of confidentiality may improve screening and
      treatment of HIV-infected inmates.

PMID- 15453179
TI  - Perinatal health service use by women released from jail.
AB  - Few studies have examined health care access for the growing population of
      pregnant women who cycle in and out of urban jails. The present study compared
      use of Medicaid-funded perinatal services for births to women who were in jail
      during pregnancy and births to women who had been in jail, but not while
      pregnant. Jail contact during pregnancy increased the likelihood women would
      receive prenatal care (odds ratio [OR] = 5.95; 95% confidence interval [CI] 2.18
      16.23) and maternity support services (OR = 1.80; 95% CI 1.12-2.88), but was
      associated with fewer total prenatal and support visits. Jail contact during a
      previous pregnancy was associated with fewer prenatal care visits, more support
      service visits, and longer time receiving case management. Jail settings can
      become a place of coordination between public health and criminal justice
      professionals to ensure that pregnant women receive essential services following
      release. Service coordination may increase women's engagement in health services
      during future pregnancies, with or without subsequent incarceration.

PMID- 15453180
TI  - Providers' perspectives and beliefs regarding transition to adult care for
      adolescents with sickle cell disease.
AB  - Until recently, few children with chronic illnesses such as sickle cell disease
      (SCD) lived past late adolescence. Substantial reductions in mortality mean a
      growing number of adolescents with SCD reach adulthood. Consensus among
      researchers and health care providers (HCP) from multiple disciplines is that
      critical attention to and more empirical research on the transition from
      pediatric to adult care is needed. We address the following questions: (1) How do
      pediatric and adult providers demonstrate involvement in transition? (2) What is
      expected of adolescents when they move to adult care? and (3) Do providers think
      there is a need for a systematic transition program? A cross-sectional, multi
      format survey research study utilizing open-ended and forced-choice questions was
      conducted to compare responses between pediatric and adult providers from
      multiple disciplines. Data were collected from 227 HCP in three waves.
      Significant bivariate results (p < 0.05) reflected differing opinions regarding
      transition expectations and program need, especially among female providers,
      those practicing in urban areas, and providers who treat both adolescent and
      adult clients in comparison with their counterparts. Discussion includes
      implications for program development, social service and public health practice,
      and future research.

PMID- 15453181
TI  - Patterns of hospital-based pediatric care across diverse ethnicities: the case of
      pneumonia.
AB  - Few studies have evaluated racial disparities with respect to process and outcome
      measures for pneumonia. We evaluated disparities with respect to process measures
      in addition to clinical and financial outcome measures in a pediatric population
      from 0 to 18 years of age. The data showed that minority populations were
      admitted at younger ages and were more likely to be admitted through the
      emergency department than their white counterparts. Substantial variation exists
      with respect to patterns of care and outcomes for pneumonia in pediatric patients
      among different ethnic/racial groups. Differences in outcomes may be associated
      with several factors, including variations in quality of care across different
      hospital settings, characteristics related to disease severity among different
      ethnic groups, and other unidentified factors. Further research is needed to
      clearly define how differences with respect to quality of care, access to care,
      disease severity, and care-seeking behaviors contribute to differences in
      outcomes across different ethnic groups.

PMID- 15453182
TI  - Patient health status and appointment keeping in an urban community health
      center.
AB  - This study examines the relationship between patient health status and the
      likelihood of missing appointments in a community health center serving low
      income patients. Medical records of 465 adult patients scheduled to be seen
      during one week in February 1999 were audited for an 18-month period. Seventy
      three percent of patients failed to keep one or more appointments; 43% missed one
      or two; 30% missed three or more. Health status measures significantly associated
      with missing appointments included depression (p = 0.03), anxiety/panic disorder
      (p = 0.03), and using tobacco (p = <0.001). Linear regression analysis indicated
      that the number of appointments scheduled and of diagnosed psychological
      conditions, as well as patient age were significant predictors of missed
      appointments. Patient appointment keeping is predictable; definable, measurable
      characteristics of patients can contribute to setting priorities for customizing
      interventions.

PMID- 15453183
TI  - Recent progress in microbial cultivation techniques.
AB  - Recent advances in the improvement of microbial cultivation are reviewed, with
      emphasis on biochemical engineering techniques as a means of obtaining high
      production rate of bioproduct. Possible uses of high cell density culture include
      their use in food industry as well as in the production of new medicines and in
      biotechnology. Concentration of microorganisms using a hollow fiber membrane or
      centrifuge, and increase in cell density by controlling the pH, dissolved oxygen,
      or carbon source concentrations of the culture broth with control algorithms are
      discussed. In a culture of filamentous microorganisms the mycelial morphology is
      hard to define and it is difficult to quantify its amount, and this is one of the
      bottlenecks hampering the improvement of production rate. Specific features of
      mycelial cultivation in the presence of highly pulpy mycelia and entangled
      pellets are scrutinized by visual inspection through a microscope that is linked
      to a computer, and using software that can characterize the mycelial morphology.
      Image analysis technology for analyzing the mycelial image captured by a digital
      camera is a potential tool for morphological analysis, including analysis of the
      morphological development of filamentous microorganisms.

PMID- 15453184
TI  - Clarification of interactions among microorganisms and development of co-culture
      system for production of useful substances.
AB  - Co-culture systems containing two microorganisms for the production of useful
      substances are described. We developed a novel co-culture system composed of two
      fermentors and two microfiltration modules. The proposed co-culture system
      allowed regulation of the dissolved oxygen concentration at a level suitable for
      an individual microorganism in each fermentor, as well as the successful exchange
      of culture medium between two fermentors. By co-culture, using a combination of
      Pichia stipitis and Saccharomyces cerevisiae, ethanol was produced efficiently
      from a mixture of glucose and xylose. Moreover, the useful probiotic cells were
      simultaneously produced with a high productivity by our co-culture using a
      combination of Bifidobacterium and Propionibacterium. Kefiran production by
      Lactobacillus kefiranofaciens alone under the culture conditions, established by
      mimicking the presence and activities of yeast cells in kefir grains, was also
      investigated. The results obtained showed that under the culture conditions
      established by mimicking the actions of yeast cells on L. kefiranofaciens in
      kefir grains, the amount of kefiran produced was enhanced, even when the lactic
      acid bacterium alone was used.

PMID- 15453185
TI  - High rate production of hydrogen/methane from various substrates and wastes.
AB  - To treat soluble and solid wastes and recover energy from them, high rate methane
      fermentation, especially using the UASB (upflow anaerobic sludge blanket)
      reactor, and hydrogen fermentation using various microorganisms and microbial
      consortia have been investigated intensively in Japan. In this chapter, recent
      works on high rate methane fermentation in Japan are reviewed, focusing on: 1)
      basic studies into the applicability of the UASB reactor for various substrates
      such as propionate, lactate, ethanol, glucose and phenol; 2) its applications to
      unfeasible conditions, such as lipid and protein containing wastes, low
      temperature and high salt-containing wastes; 3) progress made in the field of
      advanced UASB reactors, and; 4) research into methane fermentation from solid
      wastes, such as from cellulosic materials, municipal sewage sludge, and mud
      sediments. Following this, although hydrogen fermentation with photosynthetic
      microorganisms or anaerobic bacteria was researched, for this review we have
      focused on fermentative hydrogen production using strictly or facultative
      anaerobes and microbial consortia in Japan, since high rate production of
      hydrogen-methane via a two-stage process was judged to be more attractive for
      biological hydrogen production and wastewater treatments.

PMID- 15453186
TI  - Bacterial capsular polysaccharide and sugar transferases.
AB  - Capsular polysaccharides (CPs) of several pathogenic bacteria are thought to be
      good materials for the development of new therapeutic reagents. These
      polysaccharides can be used as vaccines against infection of pathogenic bacteria
      and are also useful as inhibitors for disease caused by aberrant and abnormal
      cell-cell interaction, such as cancer metastasis and inflammation. Since
      bacterial CPs are diverse in structure and these bacteria have a variety of sugar
      transferases responsible for the synthesis of CPs, bacterial CP synthesis (cps)
      genes have attracted much interest as a source of glycosyltransferases useful for
      glycoengineering. In this review, we describe physiological effects of the
      bacterial CPs on mammalian cells, and the structure and function of the cps
      genes, by focusing on group B streptococci, Streptococcus agalactiae type Ia and
      Ib, that produce high-molecular weight polysaccharides consisting of the
      following pentasaccharide repeating units: -->4)-[alpha-D-NeupNAc-(2-->3)-beta-D
      Galp-(1-->4)-beta-D-GlcpNAc-(1-->3)]-beta-D-Galp-(1-->4)-beta-D-Glcp-(1--> and -
      >4)-[alpha-D-NeupNAc-(2-->3)-beta-D-Galp-(1-->3)-beta-D-GlcpNAc-(1-->3)]-beta-D
      Galp-(1-->4)beta-D-Glcp-(1-->, respectively.

PMID- 15453187
TI  - Bacterial sterilization and intracellular protein release by a pulsed electric
      field.
AB  - Several biotechnological applications of high-voltage pulsed electric field (PEF)
      are introduced. Electrical breakdown or disruption of a biological membrane by
      PEF is understood to occur by electromechanical compression, which results in the
      formation of transmembrane pores. If the total area of induced pores is small in
      relation to the total surface area of the membrane, the pores are able to close
      again mainly through the diffusion of the lipid molecules and rearrangement of
      the proteins (reversible disruption). If the total area of the pores becomes
      unfavorably large, the membrane is no longer able to repair these perturbations
      (irreversible disruption), and that results in sterilization. We have
      investigated effective sterilization by using PEF-induced irreversible disruption
      of biological membranes. The treatment temperature or growth temperature was
      found to have a great effect on PEF sterilization. The shape of the treatment
      chamber also proved important for effective PEF sterilization. Therefore, a
      number of reactors having novel structures were developed. We have also verified
      that this PEF-induced reversible disruption could be utilized for the selective
      release of intracellular proteins from yeast and certain gene-engineered
      Escherichia coli. The secretion of periplasmic protein from E. coli was achieved
      during cultivation.

PMID- 15453188
TI  - Cell-free protein synthesis systems: increasing their performance and
      applications.
AB  - The Escherichia coli cell-free protein synthesis system can now be used for
      various proteins that need special requirements, such as disulfide bond formation
      between intra- and inter-molecules, hetero-dimerization, and specific chaperons.
      In addition, a novel protein library construction method termed "SIMPLEX" has
      been developed. Some applications with SIMPLEX are described. A highly efficient
      eukaryotic cell-free translation system using wheat germ extract has also been
      developed. An advanced framework for a rapid eukaryotic gene expression and
      analysis is shown.

PMID- 15453189
TI  - Enzymatic synthesis of structured lipids.
AB  - Structured lipids (SLs) are defined as lipids that are modified chemically or
      enzymatically in order to change their structure. This review deals with
      structured triacylglycerols (STGs) and structured phospholipids (SPLs). The most
      typical STGs are MLM-type STGs, having medium chain fatty acids (FAs) at the 1-
      and 3-positions and a long chain fatty acid at the 2- position. MLM-type STGs are
      synthesized by: 1) 1,3-position-specific lipase-catalyzed acyl exchange of TG
      with FA or with FA ethylester (FAEt); 2) 1,3-position-specific lipase-catalyzed
      acylation of glycerol with FA, giving symmetric 1,3-diacyl-sn-glycerol, followed
      by chemical acylation at the sn-2 position, and; 3) 1,3-position-specific lipase
      catalyzed deacylation of TG, giving 2-monoacylglycerol, followed by reacylation
      at the 1- and 3-positions with FA or with (FAEt). Enzymatic preparation of SPLs
      requires: 1) acyl group modification, and 2) head group modification of
      phospholipids. Acyl group modification is performed using lipases or
      phospholipase A2-mediated transesterification or ester synthesis to introduce
      arbitrary fatty acid to phospholipids. Head group modification is carried out by
      phospholipase D-catalyzed transphosphatidylation. A wide range of compounds can
      be introduced into the polar head of phospholipids, making it possible to prepare
      various SPLs.

PMID- 15453190
TI  - Bioprocess monitoring using near-infrared spectroscopy.
AB  - Near-infrared spectroscopy (NIR) is a nondestructive analytical technique that
      has been used for simultaneous prediction of the concentrations of several
      substrates, products and constructs in mixtures sampled from fermentation
      processes. In this chapter, we discuss applications of NIR for the monitoring of
      bioprocesses involving rice vinegar, compost, glycolipid, L-glutamic acid, lactic
      acid fermentation, mushroom cultivation, and Koji production. This includes
      detailed discussion of applications of NIR to process management of rice vinegar
      fermentation and compost fermentation. In the present study, absorbance at
      wavelengths between 400 and 2500 nm was measured at 2 nm intervals. To obtain
      calibration equations, multiple linear regression (MLR) was performed on NIR
      spectral data and conventional analysis values of a calibration sample set. To
      validate these calibration equations, they were used to calculate concentrations
      of a prediction sample set, which were then compared with concentrations measured
      by conventional methods. There was excellent agreement between the results of the
      conventional method and those of the NIR method, when both were used to analyze
      culture broth of rice vinegar fermentation and solid-state fermented compost.
      These results indicate that NIR is a useful method for monitoring and control of
      bioprocesses.

PMID- 15453191
TI  - Metabolic flux analysis based on 13C-labeling experiments and integration of the
      information with gene and protein expression patterns.
AB  - The recent progress on metabolic systems engineering was reviewed, in particular
      focusing on the metabolic flux analysis (MFA) based on the isotopomer
      distribution obtained using NMR and/or GC-MS. After the brief explanation of how
      to estimate the metabolic flux distribution (MFD) based on 13C-labeling
      experiments, the metabolic regulation analysis was made based on the protein
      expression patterns obtained by two-dimensional electrophoresis (2DE) together
      with enzyme activity data, and the gene expression patterns obtained by RT-PCR
      analysis. The particular application was considered for Escherichia coli. The
      effect of culture conditions such as different carbon sources (glucose,
      gluconate, glycerol, acetate, etc.) and different dissolved oxygen (DO)
      concentration, etc. on the metabolism was investigated. The effect of some single
      gene knockout such as pgi-, pyk-, and gnd- was also investigated. It was found to
      be quite useful to integrate the information obtained from metabolic flux
      analysis, gene and protein expressions as well as intracellular metabolite
      concentrations to understand the overall picture of metabolic regulation.

PMID- 15453192
TI  - Application of knowledge information processing methods to biochemical
      engineering, biomedical and bioinformatics fields.
AB  - In biochemical and biomedical engineering fields there are a variety of phenomena
      with many complex chemical reactions, in which many genes and proteins affect
      transcription or enzyme activity of others. It is difficult to analyze and
      estimate many of these phenomena using conventional mathematical models. Recently
      some knowledge information processing methods, such as the artificial neural
      network (ANN), fuzzy reasoning, fuzzy neural network (FNN), fuzzy adaptive
      resonance theory (fuzzy ART) and the genetics algorithm (GA), were developed in
      the computer science field and have been applied to analysis in a variety of
      research fields. In this chapter, these methods will be briefly reviewed. Next,
      the application of these methods in the biochemical field will be introduced,
      instancing two examples in actual industrial processes. In addition, the
      application in the biomedical and bioinformatics field as another attractive
      field will be reviewed. Two examples are our research such as the prediction of
      prognosis for cancer patients from DNA microarray data using FNN and gene
      clustering for DNA microarray data using fuzzy ART.

PMID- 15453193
TI  - Large-scale production of hairy root.
AB  - Many products of interest are synthesized in organized tissues, but not formed in
      suspension or callus culture. Therefore, most attention has been focused on root
      cultures. The transgenic plant,"hairy root", has brought us to dramatic
      improvements in growth rate and high content of desirable products. Since the
      roots are quite different from callus in morphology, the culture manner should be
      explored independently. By providing a growth environment, an elite hairy root
      can be a more attractive plant. Both of strain selection to generate more
      competent plants in breeding and engineering development are necessary to
      overcome various limitations. In this chapter the engineering issues involved in
      using hairy root culture are discussed, as follows. 1. Measurement of cell
      concentration on line, and a designing bioreactors for hairy root in liquid
      culture. 2. High cell density culture and its kinetic parameters. 3. Secretion of
      target products. 4. The micropropagation of the regenerated hairy root by means
      of artificial seed system. In some cases where callus and suspension culture show
      negligible productivity, organ culture will be necessary to achieve good
      formation. This study on hairy root culture indicates one of the best attempts to
      the recovery of products from the organ culture in plant biotechnology.

PMID- 15453194
TI  - Large-scale micropropagation system of plant cells.
AB  - Plant micropropagation is an efficient method of propagating disease-free,
      genetically uniform and massive amounts of plants in vitro. The scale-up of the
      whole process for plant micropropagation should be established by an economically
      feasible technology for large-scale production of them in appropriate
      bioreactors. It is necessary to design suitable bioreactor configuration which
      can provide adequate mixing and mass transfer while minimizing the intensity of
      shear stress and hydrodynamic pressure. Automatic selection of embryogenic calli
      and regenerated plantlets using image analysis system should be associated with
      the system. The aim of this chapter is to identify the problems related to large
      scale plant micropropagation via somatic embryogenesis, and to summarize the
      micropropagation technology and computer-aided image analysis. Viscous additive
      supplemented culture, which is including the successful results obtained by us
      for callus regeneration, is also introduced.

PMID- 15453195
TI  - Development of culture techniques of keratinocytes for skin graft production.
AB  - The in vitro cultures of human tissues have attracted a great deal of medical
      attention as a promising technique for repairing defective tissues in vivo. In
      the last decade many companies have been established for supplying the
      regenerated grafts by means of tissue cultures of skin, cartilage, bone and so
      on. From the viewpoint of biochemical engineering, however, the culture systems
      for these tissues are not so sophisticated nor so programmed as the submerged
      culture systems developed for microorganisms. In manufacturing skin grafts, for
      instance, the raw materials of cells harvested from patients are heterogeneous,
      and the products of cultured tissues vary in the required size for individual
      epithelial sheets. Therefore, a reliable and robust process is desired for the
      production of cultured tissues with high reproducibility and quality. This review
      focuses on the strategies for developing the culture processes of keratinocytes
      targeting the epithelial sheet production, including (i) the introduction of
      culture techniques for keratinocyte cells and survey of skin graft production as
      it is, (ii) construction of kinetic model of cell growth, (iii) evaluation of
      cell properties based on image-analyzing techniques, and (iv) design of
      bioreactor system.

PMID- 15453196
TI  - Transgenic birds for the production of recombinant proteins.
AB  - Transgenic birds were expected to be an excellent transgenic bioreactor for the
      production of recombinant pharmaceutical proteins. However, the only successful
      transgenic bioreactors have been based on mammals. We have developed two key
      techniques for obtaining transgenic birds. For bird embryo culture, we identified
      that the low rate of hatchability of cultured embryos is caused by limited oxygen
      and calcium availability. In quail embryo culture using a chicken eggshell as a
      culture vessel, hatchability increased to 80% by the supplement of calcium
      lactate in addition to oxygen aeration. A fully artificial vessel for quail
      embryo culture using a gas-permeable Teflon membrane was also designed. Although
      the hatchability was lower than that of cultures using a surrogate eggshell, we
      succeeded in hatching of bird embryos using a fully artificial vessel. For
      transgene introduction, a replication-defective pantropic retroviral vector based
      on Moloney murine leukemia virus (MoMLV) pseudotyped with vesicular stomatitis
      virus G protein (VSV-G) was injected to laid embryos at the blastodermal stage,
      and the embryos were hatched in vitro to generate G0 birds. The viral vector
      sequence was detected in the tissues of all G0 birds. The germ-line transmission
      efficiency was more than 80%. Plural copies of the transgene were inserted into
      the genome of G1 transgenic progeny.

PMID- 15453197
TI  - Functional magnetic particles for medical application.
AB  - Magnetic particles for medical applications have been developed by many
      researchers. Since magnetic particles have unique magnetic features not present
      in other materials, they can be applied to special medical techniques.
      Separation, immunoassay, magnetic resonance imaging (MRI), drug delivery, and
      hyperthermia are enhanced by the use of magnetic particles. Magnetite cationic
      liposomes (MCLs), one of the groups of cationic magnetic particles, can be used
      as carriers to introduce DNA into cells since their positively charged surface
      associates with the negatively charged DNA. MCLs can also be used as heat
      mediators for cancer therapy. Magnetic particles conjugated with tumor-specific
      antibodies have enabled tumor-specific contrast enhancement in MRI. In addition,
      antibody-conjugated magnetic particles were shown to target renal cell carcinoma
      cells, and are applicable to the hyperthermic treatment of carcinomas. It was
      also found that the hyperthermic treatment using magnetic particles induced an
      antitumor immunity. Thus, the use of magnetic particles with their unique
      features will further improve medical techniques.

PMID- 15453198
TI  - Study results: employer-based coverage of genetic counseling services.
AB  - Because advances in genetic medicine are likely to affect the cost and delivery
      of employer-sponsored health care, plan managers require a basic understanding of
      related services. By describing and analyzing a survey of health plan managers,
      the author shows where they may need more information about genetic services in
      order to negotiate coverage and make informed purchasing decisions. Given these
      current information gaps, genetic counselors may be helpful to health plan
      managers by providing information and quality assurance about genetic medicine as
      it continues to integrate itself into medical practice and as plan managers seek
      cost-containment approaches in the face of rising health care costs.

PMID- 15453199
TI  - "Any Willing Provider" laws not preempted by Employee Retirement Income Security
      Act (ERISA). Kentucky Association of Health Plans, Inc. et. al. v. Miller,
      Commissioner, Kentucky Department of Insurance.
AB  - "Any Willing Provider" laws are not preempted by ERISA because they are state
      laws regulating insurance if they are (1) specifically directed toward entities
      engaged in insurance and (2) substantially affect the risk-pooling arrangement
      between the insurer and the insured. Thus, a state may prohibit health
      maintenance organizations (HMOs) from creating exclusive "provider networks" of
      doctors, hospitals and other health care providers by excluding other providers
      who are "willing and able" to comply with all the HMO's contractual terms if the
      law meets the new two-prong test established by the Supreme Court in this case.
      The Court made a "clean break" from using the McCarran-Ferguson Act factors for
      determining whether certain practices constitute "the business of insurance,"
      when deciding when they regulate insurance for purposes of ERISA preemption.

PMID- 15453200
TI  - Disability plans--treating physician rule. Black & Decker Disability Plan v.
      Nord.
AB  - ERISA does not require the administrator of an employee welfare plan to give
      special deference to a claimant's treating physician's opinion for purposes of
      determining eligibility for disability benefits. Nevertheless, administrators may
      not arbitrarily refuse to credit a claimant's treating physician's opinion or any
      other reliable evidence.

PMID- 15453201
TI  - Social Security disability insurance benefits-eligibility. Barnhart, Commissioner
      of Social Security v. Walton.
AB  - SSA's interpretation of the Social Security Act and its regulation requiring that
      eligibility for benefits requires that an applicant be both impaired and unable
      to engage in substantial gainful activity (work) for at least 12 months was
      permitted by the act and the regulation was lawful. SSA was entitled to the
      benefit of hindsight, and even though an individual might have been awarded
      benefits under the act if the decision were made before the end of 12 months
      because the impairment and inability to work could be expected to last at least
      12 months, it could deny benefits when it makes its decision after 12 months from
      the onset of the impairment and knows the applicant was able to work after 11
      months.

PMID- 15453202
TI  - ADA--covered entities--shareholder-directors as employees. Clackamas
      Gastroenterology Associates v. Deborah Wells.
AB  - Control is the touchstone for determining whether an individual is an employee
      for the purpose of determining if a business entity is a "covered entity" subject
      to Americans with Disabilities Act (ADA). Thus, if shareholder-directors operate
      independently and manage the business, they are proprietors and not employees,
      but if they are subject to the firm's control, they are employees. All the
      incidents of the relationship must be considered with no one factor being
      decisive. The Equal Employment Opportunity Commission's (EEOC's) six relevant
      factors provide the guidelines.

PMID- 15453203
TI  - VEBAs--ordinary and necessary expenses--deductions and constructive dividends.
      Neonatology Associates, P.A. v. Commissioner of Internal Revenue.
AB  - Contributions made by professional medical corporations into voluntary employee
      benefit program plans (VEBAs), which were well in excess of the cost of the term
      life insurance provided to the participants, were not ordinary and necessary
      business expenses, and the distributions of surplus cash to owner physicians upon
      conversion to individual policies constituted constructive dividends taxable to
      the individual taxpayers.

PMID- 15453204
TI  - Medicare--substitute HMOs--reimbursement from other insurance. Care Choices HMO
      v. Engstrom.
AB  - The federal statute that permits Medicare-substitute HMOs to seek reimbursement
      from other insurers does not provide the HMOs with a private federal remedy for
      reimbursement. It permits Medicare-substitute HMOs to provide in their policies
      that they are entitled to reimbursement in cases where other insurance, such as
      the third-party liability insurance of a party responsible for causing an injury,
      is available. The HMO must sue in state court for its contractual right to
      reimbursement. It may not sue in federal court under the federal statute that
      merely allows it to provide for reimbursement in their policies.

PMID- 15453205
TI  - When and how to use ABNs.

PMID- 15453206
TI  - No doctor is a data island.

PMID- 15453207
TI  - This piece of paper can boost your income.

PMID- 15453208
TI  - Bargain healthcare stocks worth buying.

PMID- 15453209
TI  - Tailoring practice guidelines for real patients.

PMID- 15453210
TI  - Beware the "advisory board" scam.

PMID- 15453211
TI  - When a parent can't live at home.

PMID- 15453212
TI  - My patients' best e-resource? Me.

PMID- 15453213
TI  - Managing petty cash is no petty matter.

PMID- 15453214
TI  - Doctors and the FTC: advice from an insider.

PMID- 15453215
TI  - It's not just what we say.

PMID- 15453216
TI  - How to handle conflict.

PMID- 15453217
TI  - Liability for nursing home care.

PMID- 15453218
TI  - Choice ideas. Fighting shy.

PMID- 15453219
TI  - The HSJ barometer...primary care trust chief executives.

PMID- 15453220
TI  - US-style commissioning. Raising Arizona.
AB  - Strategic health authorities can learn a lot about strategic vision from
      Arizona's healthcare cost containment system. The Arizona commissioners have
      greater power than primary care trusts to push through new and more effective
      models of community care. Commissioner/provider relations can be fraught as
      health plans hold out for big discounts.

PMID- 15453221
TI  - Mental health. Joined-up working.

PMID- 15453222
TI  - Finite element analysis of an osseointegrated stepped screw dental implant.
AB  - An osseointegrated stepped screw dental implant was evaluated using 2-dimensional
      finite element analysis (FEA). The implant was modeled in a cross section of the
      posterior human mandible digitized from a computed tomography (CT) generated
      patient data set. A 15-mm regular platform (RP) Branemark implant with equivalent
      length and neck diameter was used as a control. The study was performed under a
      number of clinically relevant parameters: loading at the top of the transmucosal
      abutment in vertical, horizontal, and 45 degrees oblique 3 orientations. Elastic
      moduli of the mandible varied from a normal cortical bone level (13.4 GPa) to a
      trabecular bone level (1.37 GPa). The study indicated that an oblique load and
      elastic moduli of the cortical bone are important parameters to the implant
      design optimization. Compared with the cylindrical screw implant, the maximum von
      Mises stress of the stepped screw implant model was 17.9% lower in the trabecular
      bone-implant area. The study also showed that the stepped screw implant is
      suitable for the cortical bone modulus from 10 to 13.4 GPa, which is not
      necessarily as strict as the Branemark implant, for which a minimum 13.4 GPa
      cortical bone modulus is recommended.

PMID- 15453223
TI  - The use of ballclip attachments with an implant-supported primary-secondary bar
      overdenture.

PMID- 15453224
TI  - Implant plastic surgery: a review and rationale.
AB  - Implant dentistry has been established as a predictable treatment modality with
      high clinical success rates. Esthetic considerations of implant restorations have
      been gaining increased interest over the years. The role of periodontal plastic
      surgical procedures in the creation and maintenance of peri-implant soft tissue
      heights to facilitate better esthetics has become more popular. The available
      plastic surgery procedures and their clinical applications are reviewed in this
      article. Emphasis is placed on factors to consider for proper case selection and
      ideal treatment planning.

PMID- 15453225
TI  - Reversible and irreversible peri-implant lesions: report and etiopathogenic
      analysis of 7 cases.
AB  - The purpose of this report is to review the aberrations in the integration
      process of cylindrical endosseous implants, though such aberrations are seldom
      observed. These issues are treated according to the following scheme: (1)
      infectious lesions, which consist of peri-implantitis, intraosseous infectious
      foci, and septic voids; (2) transitory lesions; (3) lesions related to occlusal
      overload; and (4) healing defects. In this report, we illustrate these categories
      with patient histories and discuss the clinical findings and etiopathogenies.

PMID- 15453226
TI  - An instrument for the optimal guiding of osseointegrated dental implants.
AB  - The purpose of this study was to design an instrument for the optimal guiding of
      osseointegrated implants intraoperatively to achieve parallelism or desired
      angulations. Seven patients (4 males and 3 females) were enrolled in the
      investigation. They ranged in age from 44 to 61 years. Using an instrument
      designed by the senior author that permitted optimal guiding of the osteotomy
      instruments (33 Osteofix Oy, Oulu, Finland) we placed in these patients, root
      form, single stage implants. The difference in angulations between the first and
      the remaining implants was measured using the abutment replicas on the working
      models. It was found that the mean deviation angle between the first and the
      adjacent implant replicas was 2.2 degrees (SD = 0.4 degrees). The largest
      deviation angles were 2.3 degrees (SD = 0.5 degrees) and 3.1 degrees (SD = 0.8
      degrees). The study indicated that the instrument had been designed in a
      functional manner and that all implants in such relationships can be inserted
      into their desired positions, either parallel to one another or with the desired
      angle for the planned prostheses.

PMID- 15453227
TI  - Leadership: the professional responsibility of all RNs.

PMID- 15453228
TI  - ANNA's ESRD Education Day promotes legislative understanding of kidney disease
      care.

PMID- 15453229
TI  - Writing and designing readable patient education materials.
AB  - Functional illiteracy is a problem often overlooked by nurses. Although the
      average adult in the United States cannot read above the eighth-grade level, most
      patient education materials are written on a high-school or college reading
      level. If patients cannot read educational materials, then there is little hope
      of them using or understanding the information. Strategies for improving the
      readability of education materials specific to the needs of nephrology patients
      are discussed in this article.

PMID- 15453230
TI  - Self-management, knowledge, and functioning and well-being of patients on
      hemodialysis.
AB  - Past research suggests that patients' self-management behavior and knowledge
      about their condition/treatment may impact functioning and well-being. Specific
      self-management activities used by patients on hemodialysis have included
      cooperative/participatory and protective/proactive strategies. In this cross
      sectional study, measures of self-management and knowledge were administered to
      372 patients on hemodialysis-from 17 dialysis facilities. Findings suggest that
      the patients studied were low self-managers. The most commonly used self
      management strategies were the cooperative/participatory activities of self-care
      during hemodialysis and shared responsibility in care. Multiple linear regression
      showed self-care during hemodialysis to be positively associated with physical
      functioning, measured by the SF-12 Physical Component Summary (PCS-12) scale.
      Age, diabetes, and two protective/proactive strategies (selective symptom
      management and assertive self-advocacy) were negatively associated with the PCS
      12. Selective symptom management was also negatively associated with mental
      health functioning measured by the SF-12 Mental Component Summary (MCS-12),
      whereas patient knowledge of kidney disease/treatment was positively associated
      with the MCS-12. Because past research has shown the SF-36 PCS and the MCS scores
      to be associated with mortality and hospitalizations, using
      cooperative/participatory self-management behaviors, minimizing the need for
      protective/proactive strategies, and increasing patients' knowledge of kidney
      disease may have long-term benefits.

PMID- 15453231
TI  - Nephrology nurses in a new role: diagnostic and interventional nephrology.
AB  - Diagnostic and interventional nephrology is a growing subspecialty of nephrology.
      Increasingly, procedural care of nephrology patients is being managed by
      nephrologists trained in this area. As a result, new opportunities have been
      created for nephrology nurses as they assist these interventionists in the
      administration of care in diagnostic and interventional nephrology. This article
      describes the components of a diagnostic and interventional nephrology program,
      the initiation of such a program at a university center, and the role of
      nephrology nursing personnel in this rapidly developing area.

PMID- 15453232
TI  - Renal regulation of extracellular fluid volume and osmolality.
AB  - In order for our body cells to function properly, they must be surrounded in
      extracellular fluid that is relatively constant with regard to osmolality. The
      kidneys, in concert with neural and endocrine input, regulate the volume and
      osmolality of the extracellular fluid by altering the amount of sodium and water
      excreted. This is accomplished primarily through alterations in sodium and water
      reabsorption, the mechanisms of which differ within each nephron segment.

PMID- 15453233
TI  - The role of real-time ultrasound and physical examination measurements in
      placement of cuffed-tunneled hemodialysis catheters.
AB  - The portability of non-invasive ultrasound has resulted in an expansion of its
      utilization into a variety of clinical settings. Since ultrasound is recommended
      for initial vein cannulation during catheter placement, it is conceivable that
      ultrasound may also be used to verify catheter position. The purpose of this
      study was to evaluate the feasibility of tunneled hemodialysis catheter placement
      without the use of fluoroscopy. Determination of appropriate catheter length
      using physical exam measurements and verification of correct placement using
      portable ultrasound were examined. A total of 61 subjects, 31 with and 30 without
      a tunneled hemodialysis catheter underwent echocardiographic examination using
      the SonoSite 180PLUS (HCU; Bothell, WA) portable ultrasound. The investigator,
      using dynamic ultrasound imaging, was able to identify correct position in 30 of
      the 31 subjects with catheters. Still echocardiographic images were reviewed by
      two cardiologists and determined to be inconclusive. Physical examination
      measurements correlated well with the interventional radiologist guide-wire
      measurements (p < .01; r = 0.65) and concluded to be a useful method for
      determining appropriate cuffed catheter length.

PMID- 15453234
TI  - Stress among nephrology nurses in Northern Ireland.
AB  - This qualitative study was designed to explore the perception of stress of
      nephrology nurses within a major nephrology center in Northern Ireland. The
      information was collated from a sample of 10 nurses through semi- structured
      taped interviews. The findings indicate that stress was derived from the
      following categories: job content, resource issues, professional concerns,
      professional working relationships, and extrinsic factors. The coping mechanisms
      adopted by these nurses are also discussed. The actual dialogue of the nurses is
      included to provide depth and substance to the categories and themes, and a
      discussion is presented of the relationship of these findings to theory. These
      findings have relevant implications for nursing practice, nursing education, and
      nursing administration.

PMID- 15453235
TI  - Adherence to the dialysis prescription: partnering with patients for improved
      outcomes.
AB  - Nonadherence is common in the U.S. dialysis population. No single strategy has
      been definitely proven to yield universal and/or lasting improvements in
      adherence. However, using a patient-centered approach, including the removal of
      barriers to adherence, ongoing education, and cognitive behavioral strategies,
      may generate increased opportunities for patients and the nephrology staff to
      improve both adherence and outcomes.

PMID- 15453236
TI  - A family decision to discontinue dialysis treatment for a parent: an advanced
      practice nurse (APN) guided process.
AB  - Nephrology APNs play a major role in every aspect of caring for dialysis patients
      and often assume a leadership role with respect to patient and/or family
      concerns. It is always difficult to witness individuals and families struggle
      with making end-of-life decisions for a loved one. The middle-range theory of
      caregiver stress offers a way to utilize the RAM in the context of family
      caregiver experiences with a chronically ill relative. Additionally, there are a
      number of tools, such as the RPA/ASN guidelines, available for the APN working in
      nephrology. These guidelines provide a structured, systematic pathway for
      creating a plan of action. In the case of A.G., the intended outcomes were
      achieved largely due to the leadership role of the CNS in ensuring that there was
      a coordinated, dedicated, and comprehensive renal team approach. There were open
      lines of communication evident between all disciplines and the family throughout
      A.G.'s illness. His family received the full benefit of all available resources,
      and was able to make an informed decision with regard to the care of their
      father. Support was provided for the patient and his family at the end of life,
      culminating in a good death.

PMID- 15453237
TI  - What is the responsibility of the nephrology nurse when the patient is
      chronically late? Nephrology nurses must follow the Nightingale Pledge.

PMID- 15453238
TI  - What is the responsibility of the nephrology nurse when the patient is
      chronically late? Nephrology nurses deserve respect.

PMID- 15453240
TI  - Peritoneal dialysis fact sheet.

PMID- 15453239
TI  - IV iron administration in a peritoneal dialysis clinic.

PMID- 15453241
TI  - Making a difference in end-of-life decisions.
AB  - In summary, this process is painful for family and caregivers, particularly after
      an extended relationship as the one experienced above. It requires a strong
      commitment on the part of the health care team who embrace a dignified end-of
      life process and the decisions that must be made. The health care team that cared
      so well for S.R. in life was able to assist and be part of his dignified closure.

PMID- 15453242
TI  - Health insurance: who's covered?

PMID- 15453243
TI  - Physicians as partners.

PMID- 15453244
TI  - The total service experience.

PMID- 15453245
TI  - Private matters.

PMID- 15453246
TI  - Make it personal.

PMID- 15453247
TI  - Model behavior.

PMID- 15453248
TI  - Start small--think big.

PMID- 15453249
TI  - Steering clear of bandwagons.

PMID- 15453250
TI  - The RFID revolution.

PMID- 15453251
TI  - Doctors on display.

PMID- 15453252
TI  - Take it to the next level.

PMID- 15453253
TI  - A primer on organ donation.

PMID- 15453254
TI  - A jurisprudential analysis of government intervention and prenatal drug abuse.

PMID- 15453255
TI  - Property interests in cadaverous organs: changes to Ohio anatomical gift law and
      the erosion of family rights.

PMID- 15453256
TI  - The right to refuse: a call for adequate protection of a pharmacist's right to
      refuse facilitation of abortion and emergency contraception.

PMID- 15453257
TI  - Resolving disputes over excess frozen embryos through the confines of property
      and contract law.

PMID- 15453258
TI  - Can Cleveland Clinic Health System be trusted: whether a proposed merger or
      acquisition by Cleveland Clinic Health System will substantially impair the
      competitive health care market in northeast Ohio resulting in a violation of
      federal antitrust statutes.

PMID- 15453259
TI  - Influence of hypotonic shock on glutamate and GABA uptake in rat brain
      synaptosomes.
AB  - Hyponatremia leads to hyperexcitability of neurons, seizures, and coma. It is
      well established that uptake of neurotransmitters is a sodium-dependent process.
      Therefore, we suggest that inhibition of neurotransmitter uptake can lead to the
      clinical manifestations of hyponatremia. Decreasing of sodium concentration down
      to 92 mM in incubation medium, which corresponds to lowering the osmolarity down
      to 230 mOsm/l, leads to a 45% decrease in glutamate uptake and a 46% decrease in
      gamma-aminobutyric acid (GABA) uptake. However, this effect was mediated by the
      nonspecific lowering of osmolarity rather than by decreasing sodium
      concentration. Hypotonic shock was able to reduce glutamate uptake in the
      presence of protein kinase inhibitors staurosporine and genistein, the
      phosphatase inhibitor okadaic acid, the phosphatidylinositol 3-kinase inhibitor
      wortmannin, and cytoskeleton modulators colchicine and cytochalasin B. Therefore,
      we suggest that intracellular signaling is not mediating the effect of osmolarity
      reduction on neurotransmitter uptake.

PMID- 15453260
TI  - Alkalinization-induced changes in intracellular calcium in rat spinal cord
      neurons.
AB  - It is well-known that pH changes can influence a lot of cellular processes. In
      this work, we have specifically studied the influence of alkalinization, which
      can be developed in spinal cord neurons during hyperventilation (respiratory
      alkalosis) and chronic renal failure (metabolic alkalosis) on calcium
      homeostasis. Application of Tyrode solution with increased pH (pH = 8.8) to
      secondary sensory neurons isolated from rat spinal dorsal horn induced elevation
      of intracellular free calcium concentration in the cytosol ([Ca2+]i) if applied
      after membrane depolarization. Repetitive application of alkaline solution led to
      disappearance of such elevations. Depletion of endoplasmic reticulum (ER) calcium
      stores by 30 mM caffeine almost completely blocked the effect of elevated
      extracellular pH. If caffeine-induced [Ca2+]i transients were evoked during
      alkalinization, their amplitudes were decreased by 41%. Preapplication of 500 nM
      ionomycin resulted in disappearance of alkalinization-induced [Ca2+]i transients,
      whereas prolonged applications (for 20 min) of 200 nM thapsigargin, a blocker of
      Ca2+ ATPase of the endoplasmic reticulum, resulted in disappearance of the rapid
      phase of the [Ca2+]i transients induced by alkalinization. Preapplication of the
      mitochondrial protonophore CCCP (10 microM) also induced changes in the
      alkalinization-induced calcium response--it lost its peak and was transformed
      into an irregular wave terminating in several seconds. The data obtained indicate
      that alkalinization induces an increase of [Ca2+]i level in the investigated
      neurons via a combined action of both intracellular Ca2+-accumulating structures-
      the endoplasmic reticulum and mitochondria. This suggestion was supported by
      morphological data that both structures in these neurons are tightly connected
      and may interact during release of accumulated calcium ions.

PMID- 15453261
TI  - Fos expression in the rat brain after intraperitoneal injection of Staphylococcus
      enterotoxin B and the effect of vagotomy.
AB  - The current study was designed to locate the neuronal activation in rat brain
      following intraperitoneal injection of Staphylococcus enterotoxin B (SEB) and
      observe the consequence of preliminary subdiaphragmatic vagotomy on SEB-induced
      brain Fos expression to clarify the role of the vagus nerve in sensation and
      transmission of abdominal SEB stimulation. The results showed that
      intraperitoneal SEB (1 mg/kg) induced a robust Fos expression in widespread brain
      areas. A significant increase of Fos immunoreactive cells were observed in the
      solitary tract nucleus, locus ceruleus, lateral parabrachial nucleus,
      ventrolateral part of central gray, medial amygdaloid nucleus, central amygdaloid
      nucleus, ventromedial part of thalamus, dorsomedial part of thalamus,
      hypothalamic paraventricular nucleus, lateral habenula, and lateral septum
      nucleus following SEB challenge. In hypothalamic paraventricular nucleus, in
      addition to the dense Fos expression in the parvocellular portion, some Fos
      positive cells were also observed in the anterior magnocellular nucleus of the
      complex. Double immunofluorescence studies showed that these Fos-immunoreactive
      cells were mostly oxytocinergic. The results also showed that subdiaphragmatic
      vagotomy largely attenuated, but not totally abrogated, the brain Fos expression
      induced by abdominal administration of SEB. Our data suggest that peripheral SEB
      stimulation can induce activation of neurons in widespread brain areas and that
      the vagus plays a crucial role in transmitting the signal of abdominal immune
      stimulation to the brain.

PMID- 15453262
TI  - Exposure of rat optic nerves to nitric oxide causes protein S-nitrosation and
      myelin decompaction.
AB  - This study investigates the effect of nitric oxide (NO) on both the chemical
      modifications of CNS proteins and the architecture of the myelinated internode.
      Incubation of rat optic nerves for 2 h with 1 mM concentration of the NO-donors S
      nitroso-N-acetyl-penicillamine (SNAP), ethyl-2-[hydroxyimino]-5-nitro-3
      hexeneamide (NOR-3), and 4-phenyl-3-furoxan carbonitrile (PFC) led to
      decompaction of myelin at the level of the intraperiod line (IPL). In contrast,
      incubation with 1 mM sodium nitroprusside, which slowly releases NO, sodium
      nitrite, and N-nitrosopyrrolidine failed to cause myelin disassembly. This
      suggests that free NO and/or some of its direct oxidation products (e.g., N2O3)
      are the active molecular species. NO-induced alterations in myelin architecture
      could not be assigned to protein or lipid degradation, lipid peroxidation, ATP
      depletion, calcium uptake, protein nitration, protein carbonylation, and nerve
      depolarization. NO-treatment, however, resulted in the S-nitrosation of a number
      of proteins. In myelin, one of the major S-nitrosated substrates was identified
      as proteolipid protein (PLP), an abundant cysteine-rich protein that is
      responsible for IPL stabilization. Peripheral nervous system myelin, whose
      stability depends on proteins other than PLP, was not decompacted upon incubation
      of sciatic nerves with SNAP. It is proposed that NO-mediated nitrosation of
      sulfhydryl groups is likely to interfere with the normal function of PLP and
      other important CNS myelin proteins leading to the structural demise of this
      membrane. These findings are relevant to multiple sclerosis and other
      inflammatory demyelinating disorders where both excessive NO production and
      myelin instability are known to occur.

PMID- 15453263
TI  - Local perfusion of nicotine differentially modulates somatodendritic dopamine
      release in the rat ventral tegmental area after nicotine preexposure.
AB  - We examined the effects of nicotine perfusion into the ventral tegmental area
      (VTA) on extracellular dopamine (DA) levels in rats using in vivo microdialysis.
      Local perfusion with nicotine for 80 min (10-100 microM) modestly increased
      (approximately 105-131% of basal) the extracellular DA levels in the VTA of rats
      that had been pretreated with saline for 5 days. In animals that had been
      pretreated with nicotine for 5 days (0.3 mg/kg, s.c.), perfusion with nicotine
      for 80 min (10-100 microM) dose-dependently increased the extracellular DA levels
      in the VTA of rats and did so to a greater extent than in saline-pretreated
      animals (125-171% of basal). Co-perfusion through the dialysis probe with 100
      microM mecamylamine, a nonselective nicotinic acetylcholine receptor (nAChR)
      antagonist, or 100 microM dihydro-beta-erythroidine, a high affinity and
      competitive nAChR antagonist, attenuated the enhancement of extracellular DA
      levels produced by 100 microM nicotine alone. These results suggest that local
      nicotine challenge potentiated the somatodendritic DA release after nicotine
      preexposure by stimulation of high-affinity nAChRs in the VTA.

PMID- 15453264
TI  - Kinetics of extracellular nitroxide radical and glutamate levels in the
      hippocampus of conscious rats: cautionary note to the application of nitroxide
      radical on clinical arena.
AB  - Recently, novel applications of the nitroxide radicals have been proposed as
      antioxidant and anti-cancer agents. In view of the significance of nitroxide
      radical as a potential pharmaceutical agent for various applications in
      biological systems, it will be important to investigate further whether nitroxide
      radicals have a neurotoxicity or not. Blood-brain barrier permeable nitroxide
      radical, 3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (PCAM; five
      membered ring nitroxide radical) would provide us more important information to
      explore the neuronal excitotoxicity of nitroxide radicals on the central nervous
      system. Every rat injected with PCAM showed limbic seizure with secondary
      generalization. PCAM administration resulted in neuronal cell loss in CA1 area,
      which is closely associated with the neurotoxicity of endogenous glutamate and
      nitroxide itself. More detailed studies on their possible toxicity of nitroxide
      radicals will be needed before the prospect of moving nitroxide from the
      experimental to the clinical arena when nitroxide radicals would be used for CNS
      disease in future.

PMID- 15453265
TI  - Repeated restraint stress alters hippocampal glutamate uptake and release in the
      rat.
AB  - Glutamatergic mechanisms are thought to be involved in stress-induced changes of
      brain function, especially in the hippocampus. We hypothesized that alterations
      caused by the hormonal changes associated with chronic and acute stress may
      affect glutamate uptake and release from hippocampal synaptosomes in Wistar rats.
      It was found that [3H]glutamate uptake and release by hippocampal nerve endings,
      when measured 24 h after 1 h of acute restraint, presented no significant
      difference. The exposure to repeated restraint stress for 40 days increased
      neuronal presynaptic [3H]glutamate uptake as well as basal and K+-stimulated
      glutamate release when measured 24 h after the last stress session. Chronic
      treatment also caused a significant decrease in [3H]glutamate binding to
      hippocampal membranes. We suggest that changes in the glutamatergic system are
      likely to take part in the mechanisms involved in nervous system plasticity
      following repeated stress exposure.

PMID- 15453266
TI  - Gadolinium inhibition of ecto-nucleoside triphosphate diphosphohydrolase activity
      in Torpedo electric organ.
AB  - Ecto-nucleoside triphosphate diphosphohydrolases (E-NTPDases) are widely
      expressed enzymes implicated in the modulation of nucleotide cell signaling. They
      dephosphorylate either ATP or ADP in the presence of divalent cations, and
      efforts have been made to identify efficient inhibitors. E-NTPDase activity has
      been described in Torpedo electric organ electrocytes. We show here that
      gadolinium, an established blocker of stretch-activated channels, efficiently
      inhibits E-NTPDase activity of Torpedo electric organ (Ki = 3 microM for ATPase)
      as well as apyrase from potato tuber, frequently used in inhibition experiments.
      To our knowledge, gadolinium is the most potent inhibitor described to date for
      both membrane-bound and soluble E-NTPDases.

PMID- 15453267
TI  - Parkin transcript variants in rat and human brain.
AB  - Alternative splicing has an important role in expanding protein diversity. We
      have identified complementary DNA species from adult rat and fetal human brain
      encoding seven new splice variants of parkin, a gene mutated in autosomal
      recessive juvenile parkinsonism (ARJP). Alternative splicing affects almost all
      previously characterized exons, plus 3 new exons of 72, 156, and 180 nucleotides.
      This creates the potential to express hundreds of different isoforms. The encoded
      parkin isoforms have different amino acid composition, post-translational
      modifications, and, most important, molecular architectures. They diverge for the
      presence or absence of the ubiquitin-like domain, one or two C3HC4 ring fingers,
      the in-between ring fingers (IBR) domain, and a thiol proteases active site,
      which has not been previously characterized. Distinct expression patterns occur
      in primary cultures of neuronal and glial cells. Extensive splicing of parkin
      produces regional and structural diversity and may have important implications
      for the pathogenetic mechanisms underlying ARJP.

PMID- 15453268
TI  - Dual effect of diazepam on cGMP levels in rat brain slices.
AB  - The effect of diazepam on NO-mediated cGMP synthesis was studied in rat brain
      slices. It was found that diazepam dose-dependently decreased cGMP synthesis in
      cerebellar slices, with an inhibition of 90% at 1 mM diazepam. cGMP levels in the
      presence of diazepam were not restored to control levels by the addition of 0.1
      mM sodium nitroprusside, whereas the decrease in cerebellar cGMP levels induced
      by 0.1 mM L-NAME was restored by the simultaneous application of NO-donors. In
      addition to the decrease of cGMP levels in neuronal structures induced by 1 mM
      diazepam, we observed increased cGMP immunoreactivity in glial cells in the
      cerebellum, the hippocampus, and the cerebral cortex. The significance of this
      observation is discussed.

PMID- 15453269
TI  - Cyclooxygenase-3 gene expression in Alzheimer hippocampus and in stressed human
      neural cells.
AB  - The cyclooxygenase (COX) superfamily of prostaglandin synthase genes encode a
      constitutively expressed COX-1, an inducible, highly regulated COX-2, and a COX-3
      isoform whose RNA is derived through the retention of a highly structured, G + C
      rich intron 1 of the COX-1 gene. As generators of oxygen radicals, lipid
      mediators, and the pharmacological targets of nonsteroidal anti-inflammatory
      drugs (NSAIDs), COX enzymes potentiate inflammatory neuropathology in Alzheimer's
      disease (AD) brain. Because COX-2 is elevated in AD and COX-3 is enriched in the
      mammalian CNS, these studies were undertaken to examine the expression of COX-3
      in AD and in [IL-1beta + Abeta42]-triggered human neural (HN) cells in primary
      culture. The results indicate that while COX-2 remains a major player in
      propagating inflammmation in AD and in stressed HN cells, COX-3 may play
      ancillary roles in membrane-based COX signaling or when basal levels of COX-1 or
      COX-2 expression persist.

PMID- 15453270
TI  - Uptake and metabolism of serotonin by ependymal primary cultures.
AB  - Serotonin uptake and metabolism was studied in ependymal primary cultures.
      Serotonin uptake was facilitated by two different systems, one of which was the
      neuronal serotonin transporter SERT, exhibiting a Vmax value of 3.8+/-0.1 pmol x
      min(-1) x (mg protein)(-1) and an apparent Michaelis-Menten constant of 0.41+/
      0.03 microM. The main product of metabolism was 5-hydroxyindole acetic acid,
      which resulted from the action of monoamine oxidase A. This enzyme showed a
      maximal rate of 0.85+/-0.02 nmol x min(-1) x (mg protein)(-1) and a Michaelis
      Menten constant of 78+/-5 microM. Ependymal cells were able to dispose of
      extracellular serotonin with initial rates of approximately 600 pmol x min(-1) x
      (mg protein)(-1) and of 4 pmol x min(-1) x (mg protein)(-1) when challenged with
      500 microM and 1 microM extracellular serotonin, respectively. Ependymal cells
      are concluded to facilitate the "sink" action of the CSF by removing waste
      compounds upon passing of the fluid from the parenchymal extracellular space into
      the ventricular system.

PMID- 15453271
TI  - Structure-related oxidative damage in rat brain after acute and chronic
      electroshock.
AB  - The role of oxidative stress in electroconvulsive therapy-related effects is not
      well studied. The purpose of this study was to determine oxidative stress
      parameters in several brain structures after a single electroconvulsive seizure
      or multiple electroconvulsive seizures. Rats were given either a single
      electroconvulsive shock or a series of eight electroconvulsive shocks. Brain
      regions were isolated, and levels of oxidative stress in the brain tissue
      (cortex, hippocampus, striatum and cerebellum) were measured. We demonstrated a
      decrease in lipid peroxidation and protein carbonyls in the hippocampus,
      cerebellum, and striatum several times after a single electroconvulsive shock or
      multiple electroconvulsive shocks. In contrast, lipid peroxidation increases both
      after a single electroconvulsive shock or multiple electroconvulsive shocks in
      cortex. In conclusion, we demonstrate an increase in oxidative damage in cortex,
      in contrast to a reduction of oxidative damage in hippocampus, striatum, and
      cerebellum.

PMID- 15453272
TI  - Thyroid hormone influences antioxidant defense system in adult rat brain.
AB  - The objective of the current study was to find out whether thyroid hormone
      influences antioxidant defense parameters of rat brain. Several oxidative stress
      and antioxidant defense parameters of mitochondrial (MF) and post-mitochondrial
      (PMF) fractions of cerebral cortex (CC) of adult rats were compared among
      euthyroid (control), hypothyroid [6-n-propylthiouracil (PTU)-challenged], and
      hyperthyroid (T3-treatment to PTU-challenged rats) states. Oxidative stress
      parameters, such as thiobarbituric acid-reactive substances (TBA-RS) and protein
      carbonyl content (PC), in MF declined following PTU challenge in comparison to
      euthyroid rats. On the other hand, when PTU-challenged rats were treated with T3,
      a significant increase in the level of oxidative stress parameters in MF was
      recorded. Hydrogen peroxide content of MF as well as PMF of CC was elevated by
      PTU-challenge and brought to normal level by subsequent treatment of T3. Although
      mitochondrial glutathione (reduced or oxidized) status did not change following
      PTU challenge, a significant reduction in oxidized glutathione (GSSG) level was
      noticed in PMF following the treatment. T3 administration to PTU-challenged rats
      had no effect on mitochondrial glutathione status. Total and CN-resistant
      superoxide dismutase (SOD) activities in MF of CC augmented following PTU
      challenge. CN-resistant SOD activity did not change when PTU-challenged rats were
      treated with T3. Although CN-sensitive SOD activity of PMF remained unaltered in
      response to PTU challenge, its activity increased when PTU-challenged rats were
      treated with T3. Catalase activity in PMF of CC of PTU-challenged rats increased,
      whereas the activity was decreased when hypothyroid rats were treated with T3.
      Similarly, total and Se-dependent glutathione peroxidase (GPx) activities of MF
      increased following PTU challenge and reduced following administration of T3. Se
      independent GPx activity of MF and PMF and glutathione reductase activity of PMF
      decreased following PTU challenge and did not change further when rats were
      treated with T3. On the other hand, glutathione S-transferase activity of MF and
      PMF of CC did not change following PTU challenge but decreased below detectable
      level following T3 treatment. Results of the current investigation suggest that
      antioxidant defense parameters of adult rat brain are considerably influenced by
      thyroid states of the body.

PMID- 15453273
TI  - Life-long effects of perinatal asphyxia on stress-induced proteins and dynamin 1
      in rat brain.
AB  - In previous work, we have shown that perinatal asphyxia (PA) in the rat leads to
      life-long neurotransmitter deficits and impairment of cognitive functions and
      behavior. This observation made us examine protein expression in hippocampus of
      rats with PA at the end of the life span. We applied a well-documented and
      characterized animal model of PA. Pups, normoxic and asphyxiated for 20 min, were
      brought up until the age of 24 months and then were sacrificed. Hippocampal
      tissue was dissected from the brains, and proteins were run on two-dimensional
      gel electrophoresis with in-gel digestion and subsequent identification of
      proteins by MALDI-TOF followed by quantification of protein spots by specific
      software. In hippocampus of rats with PA, the stress proteins protein disulfide
      isomerase A3 precursor and stress-induced phosphoprotein-1 were significantly
      increased, whereas the microtubule-associated protein dynamin-1 was significantly
      reduced. Increased stress protein levels may represent long-term effects of PA
      or, alternatively, could reflect conditioning of the stress protein machinery
      known to occur as a neuroprotective principle following hypoxic-ischemic
      conditions. Decreased dynamin-1 levels may be considered as a long-term effect on
      the exocytotic system possibly reflecting or leading to impaired neuronal
      transport and vesicle-trafficking in PA of the rat of advanced age.

PMID- 15453274
TI  - Nicotine-induced changes in neurotransmitter levels in brain areas associated
      with cognitive function.
AB  - Nicotine, one of the most widespread drugs of abuse, has long been shown to
      impact areas of the brain involved in addiction and reward. Recent research,
      however, has begun to explore the positive effects that nicotine may have on
      learning and memory. The mechanisms by which nicotine interacts with areas of
      cognitive function are relatively unknown. Therefore, this paper is part of an
      ongoing study to evaluate regional effects of nicotine enhancement of cognitive
      function. Nicotine-induced changes in the levels of three neurotransmitters,
      dopamine (DA), serotonin (5-HT), norepinepherine (NE), their metabolites,
      homovanillic acid (HVA), dihydroxyphenylacetic acid (DOPAC), 5
      hydroxyindoleacetic acid (5-HIAA), and their precursor, L-DOPA, were evaluated in
      the ventral and dorsal hippocampus (VH and DH), prefrontal and medial temporal
      cortex (PFC and MTC), and the ventral tegmental area (VTA) using in vivo
      microdialysis in awake, freely moving, male Sprague-Dawley rats. The animals were
      treated with acute nicotine (0.5 mg/kg, s.c.) halfway through the 300-min
      experimental period. The reuptake blockers, desipramine (100 microM) and
      fluoxetine (30 microM), were given to increase the levels of NE and 5-HT so that
      they could be detected. Overall, a nicotine-induced DA increase was found in some
      areas, and this increase was potentiated by desipramine and fluoxetine. The two
      DA metabolites, HVA and DOPAC, increased in all the areas throughout the
      experiments, both with and without the inhibitors, indicating a rapid metabolism
      of the released DA. The increase in these metabolites was greater than the
      increase in DA. 5-HT was increased in the DH, MTC, and VTA in the presence of
      fluoxetine; its metabolite, 5-HIAA, was increased in the presence and absence of
      fluoxetine. Except in the VTA, NE levels increased to a similar extent with
      desipramine and fluoxetine. Overall, nicotine appeared to increase the release
      and turnover of these three neurotransmitters, which was indicated by significant
      increases in their metabolites. Furthermore, DA, and especially HVA and DOPAC,
      increased for the 150 min following nicotine administration; 5-HT and NE changes
      were shorter in duration. As gas chromatography experiments showed that nicotine
      levels in the brain decreased by 75% after 150 min, this may indicate that DA is
      more susceptible to lower levels of nicotine than 5-HT or NE. In conclusion,
      acute nicotine administration caused alterations in the levels of DA, 5-HT, and
      NE, and in the metabolism of DA and 5-HT, in brain areas that are involved in
      cognitive processes.

PMID- 15453275
TI  - [Studies of viral hepatitis before the discovery of hepatitis B virus].

PMID- 15453276
TI  - [Virion structure of hepatitis B virus].

PMID- 15453277
TI  - [Mechanisms of HBV replication].

PMID- 15453278
TI  - [Structure and function of HBV-DNA].

PMID- 15453279
TI  - [Function of HBV proteins and control of HBV replication].

PMID- 15453280
TI  - [HBV-related proteins as a marker of viral replication].

PMID- 15453281
TI  - [Mutations in pre-C/C, pre-S/S and X regions of hepatitis B virus].

PMID- 15453282
TI  - [Mutations in the epsilon sequences of hepatitis B virus].

PMID- 15453283
TI  - [YMDD motif and its significance].

PMID- 15453284
TI  - [HB vaccine escape mutant].

PMID- 15453285
TI  - [Recent advance in the study of immunopathobiology of hepatitis B virus infection
      using HBV transgenic mice].

PMID- 15453286
TI  - [Mechanism of hepatitis B virus infection in human hepatocytes].

PMID- 15453287
TI  - [Mechanism of immune surveillance against HBV infection].

PMID- 15453288
TI  - [HBV-specific immune response in hepatocyte destruction].

PMID- 15453289
TI  - [The role of dysfunction of dendritic cells in hepatitis B virus persistent
      infection].

PMID- 15453290
TI  - [Hepatitis/hepatocellular carcinoma and OPN/Eta-1].

PMID- 15453291
TI  - [Variation in HBV antigen presentation with HLA typing and course of hepatitis B
      virus infection].

PMID- 15453292
TI  - [Immunological tolerance to hepatitis B surface antigen].

PMID- 15453293
TI  - [Seroconversion of HBs antigen to anti-HBs].

PMID- 15453294
TI  - [Mechanisms of hepatitis B e antigen seroconversion from the aspect of viral
      mutation].

PMID- 15453295
TI  - [Anti-HBs escape mutants--implication of neutralization escape and diagnostic
      escape].

PMID- 15453296
TI  - [Mechanism of hepatitis B surface antigen disappearance from and reappearance in
      the serum of patients with chronic HBV infection].

PMID- 15453297
TI  - [Persistent infection of HBV--host-related factors and viral factors].

PMID- 15453298
TI  - [Hepatitis B viral infection and apoptosis].

PMID- 15453299
TI  - [HBs antigen, HBs antibody (anti-HBs)].

PMID- 15453300
TI  - [HBe antigen and HBe antibody].

PMID- 15453301
TI  - [Detection of hepatitis B core antibody (including IgM and IgA class
      antibodies)].

PMID- 15453302
TI  - [PreS antigen].

PMID- 15453303
TI  - [Hepatitis B virus specific DNA polymerase activity as a sensitive marker of
      viral replication].

PMID- 15453304
TI  - [Quantitation of HBV-DNA].

PMID- 15453305
TI  - [Determination of hepatitis B surface antigen subtypes].

PMID- 15453306
TI  - [Genotyping of hepatitis B virus by PCR using type-specific primers and
      geographic distribution of the genotypes].

PMID- 15453307
TI  - [Genotyping of hepatitis B virus genome by RFLP].

PMID- 15453308
TI  - [Differentiation of hepatitis B virus genotypes by ELISA using monoclonal
      antibodies].

PMID- 15453309
TI  - [Hepatitis B viral mutation and its clinical significance].

PMID- 15453310
TI  - [Detection of lamivudine-resistant hepatitis B virus].

PMID- 15453311
TI  - [Epidemiology of HBV: the trend from 1970 to the present].

PMID- 15453312
TI  - [Molecular epidemiology of hepatitis B virus].

PMID- 15453313
TI  - [Perinatal HBV infection and prevention of mother-to-infant transmission].

PMID- 15453314
TI  - [Intra-familial transmission of hepatitis B virus ( between husband and wife)].

PMID- 15453315
TI  - [Hepatitis B virus infection as an STD].

PMID- 15453316
TI  - [HBV infection in hospital and its prevention].

PMID- 15453317
TI  - [Hepatitis B immune serum globulin].

PMID- 15453318
TI  - [Efficacy of HB vaccine].

PMID- 15453319
TI  - [Asymptomatic carrier of hepatitis B virus--implication and mechanism of the
      occurrence].

PMID- 15453320
TI  - [Natural course and prognosis in asymptomatic carriers of hepatitis B virus].

PMID- 15453321
TI  - [Hepatitis B virus genotypes and mutations in asymptomatic carriers].

PMID- 15453322
TI  - [Management of asymptomatic HBV carriers].

PMID- 15453323
TI  - [Clinical view of acute hepatitis B].

PMID- 15453324
TI  - [Advances in the treatment of acute hepatitis B].

PMID- 15453325
TI  - [Clinical remarks on HBV subacute hepatitis and fulminant hepatitis].

PMID- 15453326
TI  - [Viral factors and host factors in pathogenesis of fulminant hepatitis, type B].

PMID- 15453327
TI  - [Fulminant hepatitis caused by HBV and superinfection by other hepatitis
      viruses].

PMID- 15453328
TI  - [Prediction of fulminant hepatitis in severe acute hepatitis B].

PMID- 15453329
TI  - [Clinical study of fulminant hepatitis B in infants caused by mother-to-infant
      infection].

PMID- 15453330
TI  - [Recent advances in the treatment of fulminant hepatitis B].

PMID- 15453331
TI  - [Introduction to chronic hepatitis type B].

PMID- 15453332
TI  - [Histopathological characteristics and clinical significance of New Inuyama
      Classification in chronic hepatitis B].

PMID- 15453333
TI  - [Clinical manifestations of hepatitis B virus genotypes].

PMID- 15453334
TI  - [Long-term outcome and prognostic factors for chronic hepatitis type B].

PMID- 15453335
TI  - [Long-term history of chronic hepatitis B virus infection in children].

PMID- 15453336
TI  - [Treatment and selection criteria for chronic hepatitis B].

PMID- 15453337
TI  - [Interferon therapy for chronic hepatitis B].

PMID- 15453338
TI  - [Lamivudine therapy for chronic hepatitis B].

PMID- 15453339
TI  - [Efficacy and problems in combination therapy using lamivudine and interferon for
      chronic hepatitis B].

PMID- 15453340
TI  - [Combination therapy of lamivudine and HB vaccine for the treatment of chronic
      hepatitis B].

PMID- 15453341
TI  - [Antiviral treatment of chronic hepatitis B with adefovir dipivoxil].

PMID- 15453342
TI  - [Entecavir therapy against hepatitis B].

PMID- 15453343
TI  - [Corticosteroid withdrawal therapy in patients with chronic hepatitis B virus
      infection].

PMID- 15453344
TI  - [Clinical aspects of liver cirrhosis, type B].

PMID- 15453345
TI  - [Development of cirrhosis after chronic hepatitis B].

PMID- 15453346
TI  - [Current status of treatment for HBV-related cirrhosis].

PMID- 15453347
TI  - [Liver transplantation for hepatitis B virus cirrhosis].

PMID- 15453348
TI  - [Molecular mechanism of HBV-related hepatocarcinogenesis].

PMID- 15453349
TI  - [Aberration in HBV genome and hepatocellular carcinoma].

PMID- 15453350
TI  - [Epidemiology of HBV related hepatocellular carcinoma in Japan].

PMID- 15453351
TI  - [Clinicopathological study of juvenile hepatocellular carcinoma with hepatitis B
      virus infection].

PMID- 15453352
TI  - [Hepatitis delta virus (HDV) virions, HDV-RNA and HDV related proteins].

PMID- 15453353
TI  - [Replication of hepatitis delta virus].

PMID- 15453354
TI  - [Divergence and heterogeneity of HDV-RNA sequences in Japan].

PMID- 15453355
TI  - [HDV genomic change and pathogenesis].

PMID- 15453356
TI  - [Hepatitis delta (D) virus infection: general aspects of epidemiology, infection
      modes and clinical picture].

PMID- 15453357
TI  - [Detection of HDV antigen and antibody].

PMID- 15453358
TI  - [Detection of HDV-RNA].

PMID- 15453359
TI  - [Structure of HAV particle].

PMID- 15453360
TI  - [Structure and function of HAV genome (RNA)].

PMID- 15453361
TI  - [Hepatitis A virus genotypes].

PMID- 15453362
TI  - [Specific and non-specific host defense system against hepatitis A virus (HAV)
      and mechanism of HAV infection].

PMID- 15453363
TI  - [Epidemic hepatitis A in Japan: background and actions to be taken].

PMID- 15453364
TI  - [Introduction to hepatitis A].

PMID- 15453365
TI  - [Association between severity of hepatitis A and variations in hepatitis A viral
      RNA].

PMID- 15453366
TI  - [Anti HAV test].

PMID- 15453367
TI  - [Detection of HAV-RNA].

PMID- 15453368
TI  - [Recurrence of hepatitis A].

PMID- 15453369
TI  - [Clinical features and pathogenesis of fulminant hepatitis caused by HAV].

PMID- 15453370
TI  - [Epidemiology and prevention of hepatitis A].

PMID- 15453371
TI  - [Hepatitis A vaccine--present condition and future problems].

PMID- 15453372
TI  - [Immune serum globulin (ISG) and its usefulness for prevention of hepatitis A].

PMID- 15453373
TI  - [Structure of HEV].

PMID- 15453374
TI  - [Structure and function of HEV genome].

PMID- 15453375
TI  - [Genetic diversity and mutation of hepatitis E virus].

PMID- 15453376
TI  - [Epidemiology of hepatitis E].

PMID- 15453377
TI  - [Hepatitis E as a zoonosis].

PMID- 15453378
TI  - [Clinical features of acute hepatitis E in Sapporo].

PMID- 15453379
TI  - [Outline of hepatitis E].

PMID- 15453380
TI  - [Detection of antibodies of HEV].

PMID- 15453381
TI  - [Detection of HEV-RNA].

PMID- 15453382
TI  - [Hepatitis E vaccine].

PMID- 15453383
TI  - [Molecular biology of TTV].

PMID- 15453384
TI  - [TT virus marker].

PMID- 15453385
TI  - [Clinical aspects of TTV infection].

PMID- 15453386
TI  - [Molecular biology of GBV-C/HGV].

PMID- 15453387
TI  - [GBV-C/HGV related viral marker and its detection].

PMID- 15453388
TI  - [GBV-C/HGV].

PMID- 15453389
TI  - [Molecular biology of SEN virus].

PMID- 15453390
TI  - [Detection of SEN-V].

PMID- 15453391
TI  - [Epidemiology of SEN virus infection--prevalence of SEN virus infection and its
      background in Japan].

PMID- 15453392
TI  - [Clinical features of SEN virus infection].

PMID- 15453393
TI  - Noninvasive positive pressure ventilation in treatment of non-COPD related acute
      respiratory failure cases.
AB  - We used Noninvasive Positive Pressure Ventilation (NPPV) in nine patients with
      acute respiratory failure (ARF), not related to chronic obstructive pulmonary
      disease (COPD). After separating the nine patients into a hypercapnic group (five
      patients) and a non-hypercapnic group (four patients), we investigated its
      effectiveness in physiological improvement and avoiding intubation. Dyspnea,
      physiological findings and ABG improved rapidly in both groups without serious
      adverse effects. The intubation avoidance rate was 66.7% (6 of 9) in total, and
      80% in the hypercapnic group and 50% in the non-hypercapnic group. The ratio of
      PaO2 to FiO2 (P/F ratio) increased during NPPV in most cases where intubation
      could be avoided. It is worthwhile to use NPPV as a bridging therapy between O2
      therapy and invasive ventilation in patients with non-COPD related ARF,
      regardless of the existence of hypercapnia. Careful monitoring of the P/F ratio
      and complications is needed to make an appropriate decision whether avoiding
      intubation will be possible or not.

PMID- 15453394
TI  - Relationship between intratumoral hemorrhage and overexpression of vascular
      endothelial growth factor (VEGF) in pituitary adenoma.
AB  - The authors investigated the relationship between hemorrhage and the expression
      of vascular endothelial growth factor (VEGF) in pituitary adenomas. The subjects
      were 39 patients with pituitary adenomas. Surgically obtained tumor tissue was
      immunohistochemically stained using antibodies against VEGF, CD-34, Ki-67, and
      anterior pituitary hormones. The expression of VEGF was graded as 0, 1+, and 2+.
      The relationship between intratumoral hemorrhage and factors such as tumor size,
      Ki-67 labeling indices, number of CD-34 positive vessels, and VEGF expression was
      examined by multivariate analysis. High-grade VEGF expression was the sole
      independent factor correlated with intratumoral hemorrhage. The number of CD-34
      positive vessels had no effect on the incidence of hemorrhage in patients with
      pituitary adenomas. In conclusion, a positive relationship between VEGF
      expression and hemorrhage in pituitary adenoma was observed. The patho-mechanical
      significance of this correlation is under investigation.

PMID- 15453395
TI  - Eyelid lengthening combined with penetrating keratoplasty for exposure
      keratopathy in Graves' ophthalmopathy--a case report.
AB  - Upper eyelid retraction is a well-known component of Graves' disease. With
      greater degrees of retraction, corneal exposure is usually increased. We report
      here on a patient with corneal perforation following exposure keratopathy due to
      upper eyelid retraction. The patient was treated with penetrating keratoplasty
      and an upper eyelid lengthening procedure using Goretex dura substitute as an
      interpositional graft material. The exposure keratopathy resolved postoperatively
      and this condition has been maintained for 45 months since the operation, with a
      good cosmetic outcome and symmetry of the palpebral fissures.

PMID- 15453396
TI  - Natural resource management to offset greenhouse gas emissions.

PMID- 15453397
TI  - Carbon stocks and projections on public forestlands in the United States, 1952
      2040.
AB  - Approximately 37% of forestlands in the conterminous United States are publicly
      owned; they represent a substantial area of potential carbon sequestration in US
      forests and in forest products. However, large areas of public forestlands
      traditionally have been less intensively inventoried than privately owned
      forests. Thus, less information is available about their role as carbon sinks. We
      present estimates of carbon budgets on public forestlands of the 48 conterminous
      states, along with a discussion of the assumptions necessary to make such
      estimates. The forest carbon budget simulation model, FORCARB2, makes estimates
      for US forests primarily based on inventory data. We discuss methods to develop
      consistent carbon budget estimates from inventory data at varying levels of
      detail. Total carbon stored on public forestlands in the conterminous US
      increased from 16.3 Gt in 1953 to the present total of 19.5 Gt, while area
      increased from 87.1 million hactares to 92.1 million hactares. At the same time
      the proportion of carbon on public forestlands relative to all forests increased
      from 35% to 37%. Projections for the next 40 years depend on scenarios of
      management influences on growth and harvest.

PMID- 15453398
TI  - Projecting large-scale area changes in land use and land cover for terrestrial
      carbon analyses.
AB  - One of the largest changes in US forest type areas over the last half-century has
      involved pine types in the South. The area of planted pine has increased more
      than 10-fold since 1950, mostly on private lands. Private landowners have
      responded to market incentives and government programs, including subsidized
      afforestation on marginal agricultural land. Timber harvest is a crucial
      disturbance affecting planted pine area, as other forest types are converted to
      planted pine after harvest. Conversely, however, many harvested pine plantations
      revert to other forest types, mainly due to passive regeneration behavior on
      nonindustrial private timberlands. We model land use and land cover changes as a
      basis for projecting future changes in planted pine area, to aid policy analysts
      concerned with mitigation activities for global climate change. Projections are
      prepared in two stages. Projected land use changes include deforestation due to
      pressures to develop rural land as the human population expands, which is a
      larger area than that converted from other rural lands (e.g., agriculture) to
      forestry. In the second stage, transitions among forest types are projected on
      land allocated to forestry. We consider reforestation, influences of timber
      harvest, and natural succession and disturbance processes. Baseline projections
      indicate a net increase of about 5.6 million ha in planted pine area in the South
      over the next 50 years, with a notable increase in sequestered carbon. Additional
      opportunities to expand pine plantation area warrant study of landowner behavior
      to aid in designing more effective incentives for inducing land use and land
      cover changes to help mitigate climate change and attain other goals.

PMID- 15453399
TI  - Monitoring forest carbon sequestration with remote sensing and carbon cycle
      modeling.
AB  - Sources and sinks of carbon associated with forests depend strongly on the
      management regime and spatial patterns in potential productivity. Satellite
      remote sensing can provide spatially explicit information on land cover, standage
      class, and harvesting. Carbon-cycle process models coupled to regional climate
      databases can provide information on potential rates of production and related
      rates of decomposition. The integration of remote sensing and modeling thus
      produces spatially explicit information on carbon storage and flux. This
      integrated approach was employed to compare carbon flux for the period 1992-1997
      over two 165-km2 areas in western Oregon. The Coast Range study area was
      predominately private land managed for timber production, whereas the West
      Cascades study area was predominantly public land that was less productive but
      experienced little harvesting in the 1990s. In the Coast Range area, 17% of the
      land base was harvested between 1991 and 2000. Much of the area was in relatively
      young, productive-age classes that simulations indicate are a carbon sink. Mean
      annual harvest removals from the Coast Range were greater than mean annual net
      ecosystem production. On the West Cascades study area, a relatively small
      proportion (< 1%) of the land was harvested and the area as a whole was
      accumulating carbon. The spatially and temporally explicit nature of this
      approach permits identification of mechanisms underlying land base carbon flux.

PMID- 15453400
TI  - Grassland management activity data: current sources and future needs.
AB  - Estimates of potential and actual C sequestration require areal information about
      various types of management activities. Forest surveys, land use data, and
      agricultural statistics contribute information enabling calculation of the
      impacts of current and historical land management on C sequestration in biomass
      (in forests) or in soil (in agricultural systems). Unfortunately little
      information exists on the distribution of various management activities that can
      impact soil C content in grassland systems. Limited information of this type
      restricts our ability to carry out bottom-up estimates of the current C balance
      of grasslands or to assess the potential for grasslands to act as C sinks with
      changes in management. Here we review currently available information about
      grassland management, how that information could be related to information about
      the impacts of management on soil C stocks, information that may be available in
      the future, and needs that remain to be filled before in-depth assessments may be
      carried out. We also evaluate constraints induced by variability in information
      sources within and between countries. It is readily apparent that activity data
      for grassland management is collected less frequently and on a coarser scale than
      data for forest or agricultural inventories and that grassland activity data
      cannot be directly translated into IPCC-type factors as is done for IPCC
      inventories of agricultural soils. However, those management data that are
      available can serve to delineate broad-scale differences in management activities
      within regions in which soil C is likely to change in response to changes in
      management. This, coupled with the distinct possibility of more intensive surveys
      planned in the future, may enable more accurate assessments of grassland C
      dynamics with higher resolution both spatially and in the number management
      activities.

PMID- 15453401
TI  - Deriving grassland management factors for a carbon accounting method developed by
      the Intergovernmental Panel on Climate Change.
AB  - Grassland management affects soil organic carbon (SOC) storage and can be used to
      mitigate greenhouse gas emissions. However, for a country to assess emission
      reductions due to grassland management, there must be an inventory method for
      estimating the change in SOC storage. The Intergovernmental Panel on Climate
      Change (IPCC) has developed a simple carbon accounting approach for this purpose,
      and here we derive new grassland management factors that represent the effect of
      changing management on carbon storage for this method. Our literature search
      identified 49 studies dealing with effects of management practices that either
      degraded or improved conditions relative to nominally managed grasslands. On
      average, degradation reduced SOC storage to 95% +/- 0.06 and 97% +/- 0.05 of
      carbon stored under nominal conditions in temperate and tropical regions,
      respectively. In contrast, improving grasslands with a single management activity
      enhanced SOC storage by 14% +/- 0.06 and 17% +/- 0.05 in temperate and tropical
      regions, respectively, and with an additional improvement(s), storage increased
      by another 11% +/- 0.04. We applied the newly derived factor coefficients to
      analyze C sequestration potential for managed grasslands in the U.S., and found
      that over a 20-year period changing management could sequester from 5 to 142 Tg C
      yr(-1) or 0.1 to 0.9 Mg C ha(-1) yr(-1), depending on the level of change. This
      analysis provides revised factor coefficients for the IPCC method that can be
      used to estimate impacts of management; it also provides a methodological
      framework for countries to derive factor coefficients specific to conditions in
      their region.

PMID- 15453402
TI  - Response of organic and inorganic carbon and nitrogen to long-term grazing of the
      shortgrass steppe.
AB  - We investigated the influence of long-term (56 years) grazing on organic and
      inorganic carbon (C) and nitrogen (N) contents of the plant-soil system (to 90 cm
      depth) in shortgrass steppe of northeastern Colorado. Grazing treatments included
      continuous season-long (May-October) grazing by yearling heifers at heavy (60-75%
      utilization) and light (20-35% utilization) stocking rates, and nongrazed
      exclosures. The heavy stocking rate resulted in a plant community that was
      dominated (75% of biomass production) by the C4 grass blue grama (Bouteloua
      gracilis), whereas excluding livestock grazing increased the production of C3
      grasses and prickly pear cactus (Opuntia polycantha). Soil organic C (SOC) and
      organic N were not significantly different between the light grazing and
      nongrazed treatments, whereas the heavy grazing treatment was 7.5 Mg ha(-1)
      higher in SOC than the nongrazed treatment. Lower ratios of net mineralized N to
      total organic N in both grazed compared to nongrazed treatments suggest that long
      term grazing decreased the readily mineralizable fraction of soil organic matter.
      Heavy grazing affected soil inorganic C (SIC) more than the SOC. The heavy
      grazing treatment was 23.8 Mg ha(-1) higher in total soil C (0-90 cm) than the
      nongrazed treatment, with 68% (16.3 Mg ha(-1)) attributable to higher SIC, and
      32% (7.5 Mg ha(-1)) to higher SOC. These results emphasize the importance in
      semiarid and arid ecosystems of including inorganic C in assessments of the mass
      and distribution of plant-soil C and in evaluations of the impacts of grazing
      management on C sequestration.

PMID- 15453403
TI  - An approach for estimating soil carbon using the National Nutrient Loss Database.
AB  - Agricultural lands have the potential to contribute to greenhouse gas mitigation
      by sequestering organic carbon within the soil. Credible and consistent estimates
      will be necessary to design programs and policies to encourage management
      practices that increase carbon sequestration. Because a nationwide survey of soil
      carbon by the wide range of natural resources and management conditions of the
      United States is prohibitively expensive, a simulation modeling approach must be
      used. The National Nutrient Loss Database (NNLD) is a modeling and database
      system designed and built jointly by the USDA- Natural Resources Conservation
      Service (NRCS) and Texas A&M University to provide science-based inferences on
      environmental impacts from changes in agricultural management practices and
      programs at the regional and national level. Currently, the NNLD simulates 16
      crops and covers approximately 1.35 x 10(8) ha. For estimating soil carbon
      sequestration, the database will be populated with approximately 1.5 x 10(6)
      field-level model runs using the EPIC (Environmental Policy Impact Calculator)
      model, which includes newly incorporated carbon equations consistent with those
      in the Century model. Each run will represent a unique situation defined by
      state, crop, climate, soil, irrigation type, conservation practice, tillage
      system, and nutrient management treatment (nutrient rate, application frequency,
      application timing, and manure category). Results are to be assigned to specific
      National Resource Inventory points (NRI) to simulate regional and national
      baselines. In this article we present the modeling approach and discuss the
      strengths and limitations.

PMID- 15453404
TI  - Carbon Management Response curves: estimates of temporal soil carbon dynamics.
AB  - Measurement of the change in soil carbon that accompanies a change in land use
      (e.g., forest to agriculture) or management (e.g., conventional tillage to no
      till) can be complex and expensive, may require reference plots, and is subject
      to the variability of statistical sampling and short-term variability in weather.
      In this paper, we develop Carbon Management Response (CMR) curves that could be
      used as an alternative to in situ measurements. The CMR curves developed here are
      based on quantitative reviews of existing global analyses and field observations
      of changes in soil carbon. The curves show mean annual rates of soil carbon
      change, estimated time to maximum rates of change, and estimated time to a new
      soil carbon steady state following the initial change in management. We
      illustrate how CMR curves could be used in a carbon accounting framework while
      effectively addressing a number of potential policy issues commonly associated
      with carbon accounting. We find that CMR curves provide a transparent means to
      account for changes in soil carbon accumulation and loss rates over time, and
      also provide empirical relationships that might be used in the development or
      validation of ecological or Earth systems models.

PMID- 15453405
TI  - Multiple benefits of carbon-friendly agricultural practices: empirical assessment
      of conservation tillage.
AB  - This study empirically estimates the multiple benefits of a subsidy policy that
      would offer payments to farmers in return for the adoption of conservation
      tillage, and compares the outcomes of alternative targeting designs for such a
      policy. The least-cost incentive payment policy schemes are simulated for the
      State of Iowa by using the data for roughly 12,000 National Resource Inventory
      (NRI) points. We use an economic conservation tillage adoption model to evaluate
      the costs of adoption and a physical process simulation model (EPIC) to estimate
      the environmental benefits due to adoption at each of the NRI points. Two
      targeting options are considered. We assess the costs and environmental
      consequences of a practice-based policy instrument (which maximizes the acres of
      land in conservation tillage, regardless of its level of environmental benefits)
      and contrast it to a performance-based instrument (which yields the highest
      amount of environmental benefits per dollar spent). Carbon sequestration in
      agricultural soils, reduction of soil erosion by wind and water, and the
      reduction in nitrogen runoff are considered as possible targets for the
      performance-based instruments. We find that the practice-based instrument
      provides high proportions of the four benefits relative to the policies that
      target the benefits directly, especially at the higher policy budget levels.
      Similarly, we estimate that targeting one of the four benefits individually
      provides high percentages of the other benefits as compared with the amounts of
      the benefits obtainable if they were targeted directly.

PMID- 15453406
TI  - Carbon sequestration in dryland ecosystems.
AB  - Drylands occupy 6.15 billion hectares (Bha) or 47.2% of the world's land area. Of
      this, 3.5 to 4.0 Bha (57%-65%) are either desertified or prone to
      desertification. Despite the low soil organic carbon (SOC) concentration, total
      SOC pool of soils of the drylands is 241 Pg (1 Pg = petagram = 10(15)g = 1
      billion metric ton) or 15.5% of the world's total of 1550 Pg to 1-meter depth.
      Desertification has caused historic C loss of 20 to 30 Pg. Assuming that two
      thirds of the historic loss can be resequestered, the total potential of SOC
      sequestration is 12 to 20 Pg C over a 50-year period. Land use and management
      practices to sequester SOC include afforestation with appropriate species, soil
      management on cropland, pasture management on grazing land, and restoration of
      degraded soils and ecosystems through afforestation and conversion to other
      restorative land uses. Tree species suitable for afforestation in dryland
      ecosystems include Mesquite, Acacia, Neem and others. Recommended soil management
      practices include application of biosolids (e.g., manure, sludge), which enhance
      activity of soil macrofauna (e.g., termites), use of vegetative mulches, water
      harvesting, and judicious irrigation systems. Recommended practices of managing
      grazing lands include controlled grazing at an optimal stocking rate, fire
      management, and growing improved species. The estimated potential of SOC
      sequestration is about 1 Pg C/y for the world and 50 Tg C/y for the U.S. This
      potential of dryland soils is relevant to both the Kyoto Protocol under UNFCCC
      and the U.S. Farm Bill 2002.

PMID- 15453407
TI  - A brief overview of carbon sequestration economics and policy.
AB  - This article provides an overview of the issues and challenges involved in
      analyzing the costs and program design for carbon sequestration. The first
      section examines some of the pitfalls of comparing the results of carbon
      sequestration cost studies and suggests some simple ways in which analysts could
      make their results more useful. The pitfalls in comparing studies include
      different definitions for the summary statistic "dollars per ton," differences in
      the type of costs that are estimated, and differences in underlying assumptions
      regarding program design and implementation. Future cost studies will benefit
      from improved treatment of leakage, general equilibrium interactions, and public
      finance interactions. The second section reviews issues related to the
      implementation of a carbon sequestration program, including which policy tools
      are available and which have received the most attention, some of the challenges
      for using those policy tools, and one alternative that has received little
      attention, but may become necessary. The discussion also provides an overview and
      analysis of the bills introduced in the last two congresses and considers the
      general policy implications of those proposals.

PMID- 15453408
TI  - Trade-based carbon sequestration accounting.
AB  - This article describes and illustrates an accounting method to assess and compare
      "early" carbon sequestration investments and trades on the basis of the number of
      standardized CO2 emission offset credits they will provide. The "gold standard"
      for such credits is assumed to be a relatively riskless credit based on a CO2
      emission reduction that provides offsets against CO2 emissions on a one-for-one
      basis. The number of credits associated with carbon sequestration needs to
      account for time, risk, durability, permanence, additionality, and other factors
      that future trade regulators will most certainly use to assign "official" credits
      to sequestration projects. The method that is presented here uses established
      principles of natural resource accounting and conventional rules of asset
      valuation to "score" projects. A review of 20 "early" voluntary United States
      based CO2 offset trades that involve carbon sequestration reveals that the
      assumptions that buyers, sellers, brokers, and traders are using to characterize
      the economic potential of their investments and trades vary enormously. The
      article develops a "universal carbon sequestration credit scoring equation" and
      uses two of these trades to illustrate the sensitivity of trade outcomes to
      various assumptions about how future trade auditors are likely to "score" carbon
      sequestration projects in terms of their "equivalency" with CO2 emission
      reductions. The article emphasizes the importance of using a standard credit
      scoring method that accounts for time and risk to assess and compare even
      unofficial prototype carbon sequestration trades. The scoring method illustrated
      in this article is a tool that can protect the integrity of carbon sequestration
      credit trading and can assist buyers and sellers in evaluating the real economic
      potential of prospective trades.

PMID- 15453409
TI  - A new approach to the link between identity and relative deprivation in the
      perspective of ageism and retirement.
AB  - Although the work force is aging, views regarding older workers remain negative.
      As a result, complaints of discrimination on the basis of age have increased.
      This situation prompts the following questions: what leads aging workers to
      acknowledge disparities between younger workers and themselves, and what are the
      consequences for aging workers of integrating into their self-image some of the
      characteristics commonly associated with their cohort? These questions are
      examined in light of a new approach to the link between identity and relative
      deprivation. The following hypotheses were included in a predictive model: the
      more individuals include characteristics of their group into their self
      descriptions, the more they experience personal deprivation when comparing their
      own situation to that of younger workers. These feelings, in turn, affect them
      during retirement in terms of lowered self-esteem and decreased satisfaction with
      their life. This model was tested among 149 young retirees. Hypotheses were
      confirmed, and it was shown that end-of-career experiences have an impact on the
      situation of young retirees. The more individuals integrated characteristics of
      aging workers, the more they felt personally deprived as a result of invidious
      comparisons with young co-workers. The latter also had a negative impact on self
      esteem and life satisfaction. Implications of results and new avenues of research
      are discussed herein.

PMID- 15453410
TI  - The volunteer and the sannyasin: archetypes of retirement in America and India.
AB  - Cultures differ in their models of the life course, including the number and the
      content of the stages through which people are expected to pass. Among those
      societies that recognize a period of retirement, the developmental tasks and
      opportunities that older individuals face are shaped by cultural ideas about
      morality, spirituality, passion, and fulfillment. This article examines two
      archetypes for retirement: the American volunteer, and the Indian sannyasin or
      "renouncer." Drawing on ethnographic data from a study of American retirees and
      descriptions of spiritual seekers in India, it considers the social roles these
      ideal types play, their self and their public images, the congruence between
      cultural expectations and their actual experiences, and the underlying values
      these people embody. It suggests that while older American volunteers view
      retirement as an entitlement, they also stress their obligation to use free time
      to pay back their society for the benefits they have enjoyed. They thus add a
      moral dimension to a period often stereotypically characterized by a "busy ethic"
      and a mindframe of self-indulgence. India's sannyasins, however, enter a life
      stage of social withdrawal and spiritual pursuit after years of fulfilling their
      adult commitments to family and community. Yet, in their self-denial and
      renunciation of worldly engagements, they model for others the religious rewards
      that can follow after leading a dutiful life. These archetypes of aging thus
      bring out their cultures' contrasting emphases on inner- versus outer
      directedness, self-development versus self-effacement, and personal freedom
      versus social responsibility.

PMID- 15453411
TI  - Knowledge of aging and life satisfaction among older adults.
AB  - Four hundred young-, middle-, and old-old adults responded to a battery of
      quizzes dealing with life satisfaction and objective aging knowledge in the
      physical, psychological, and social domains. Analyses incorporated domains of
      aging knowledge, life satisfaction, age, gender, and demographic variables. Both
      means difference and regression analyses were computed. Significant age group,
      gender, and life satisfaction differences were found for the three aging
      knowledge domains. For successive age groups, knowledge of aging decreased, with
      females knowing less than males. The greater knowledge of aging, the higher the
      life satisfaction. The demographic variables education, financial status, health,
      living arrangement, and volunteerism were significant covariates for knowledge of
      aging. Results from this study indicate that knowledge of aging in specific
      domains varies among older adult age groups and is associated with life
      satisfaction.

PMID- 15453412
TI  - The transition to retirement: stages and factors that influence retirement
      adjustment.
AB  - A set of older workers from the Raleigh-Durham-Chapel Hill, North Carolina
      metropolitan area were followed from pre-retirement to 24 months post-retirement
      in order to explore stages in retirement and the impact of social psychological,
      social background, and gender factors on the retirement adjustment. First, we
      found general support for Atchley's model of retirement adjustment (1976).
      Second, the factors that influence retirement adjustment in the data analysis
      revealed that: 1) pre-retirement self-esteem and friend identity meanings, as
      well as pension eligibility, increased positive attitudes toward retirement at
      six months, 12 months, and 24 months post-retirement; 2) retirement planning and
      voluntary retirement increased positive attitudes toward retirement earlier, but
      not later, in the first two years of retirement; 3) poor health decreased
      positive attitudes toward retirement later rather than earlier in the first two
      years of retirement; and 4) there were only limited gender effects.

PMID- 15453413
TI  - Comparison between the adsorption behaviors of an organic cation and an organic
      anion on several reversed-phase liquid chromatography adsorbents.
AB  - Adsorption data of an organic cation (propranololium chloride) and an organic
      anion (sodium 1-naphthalene sulfonate) were measured by frontal analysis on two
      RPLC adsorbents, Symmetry-C18 and XTerra-C18, with aqueous solutions of methanol
      as the mobile phases. The influence of supporting neutral salts on the adsorption
      behavior of these two ions are compared. The Henry constants are close (H
      approximately 5). The four sets of isotherm data are all well accounted for using
      the bi-Moreau model. However, the isotherms of the two ions behave differently at
      high concentrations. The initial behaviors of all the isotherms are
      antilangmuirian but remain so in a much wider concentration range for the cation
      than for the anion, due to its stronger adsorbate-adsorbate interactions on the
      low-energy adsorption sites. The retention times of both ions increase with
      increasing concentration of neutral salt in the mobile phase, suggesting the
      formation of ion-pair complexes, with Cl- for the cation and with Na+ for the
      anion. The adsorbate-adsorbate interactions vanish in the presence of salt and
      the bi-Moreau isotherm model tends toward a bi-Langmuir model. Differences in
      adsorption behavior are also observed between the cation and the anion when
      bivalent inorganic anions and cations, respectively, are dissolved in the mobile
      phase. High concentration band profiles of 1-naphthalene sulfonic acid are
      langmuirian, except in the presence of a trivalent cation, while those of
      propranolol are antilangmuirian under certain conditions even with uni- or
      divalent cations.

PMID- 15453414
TI  - An improved method for the analysis of major antioxidants of Hibiscus esculentus
      Linn.
AB  - Major antioxidants of aqueous ethanol extract from Lady's Finger (Hibiscus
      esculentus Linn) were systematically investigated in this study. Firstly, high
      performance liquid chromatography (HPLC) was applied to identify antioxidant
      peaks in a sample by spiking the sample extract with 2,2'-azino-bis-(3
      ethylbenzothiazoline-6-sulfonic acid) (ABTS) free radical, which was prepared
      from manganese dioxide and ABTS. Secondly, in order to identify the elution
      period of major antioxidant peaks, the antioxidant capacities of different
      fractions from solid-phase extraction (SPE) were measured, and the chromatograms
      of fractions were also recorded. Lastly, multiple mass spectrometry (MS(n)) was
      used to elucidate the possible chemical structures of antioxidants, and nuclear
      magnetic resonance (NMR) was further applied for structure confirmation. The
      major antioxidant compounds in lady's finger were identified to be quercetin
      derivatives and (-)-epigallocatechin using HPLC-MS and HPLC-MS(n) (n = 2-4)
      techniques. It was found that about 70% of total antioxidant activity was
      contributed by four quercetin derivatives. The structures of major antioxidants,
      which were isolated by semi-preparative RP-HPLC with two tandem C18 columns, were
      further confirmed using UV-vis absorption spectroscopy and 13C NMR spectra.
      Quercetin 3-O-xylosyl (1''' --> 2'') glucoside, quercetin 3-O-glucosyl (1''' -->
      6'') glucoside, quercetin 3-O-glucoside and quercetin 3-O-(6''-O-malonyl)
      glucoside were first identified and characterized as major antioxidants in lady's
      finger.

PMID- 15453415
TI  - Determination of aflatoxins B1, G1, B2 and G2 in medicinal herbs by liquid
      chromatography-tandem mass spectrometry.
AB  - An easy method for the determination of aflatoxins B1, G1, B2 and G2 in Rhammus
      purshiana by LC coupled to mass spectrometry has been developed. Aflatoxins were
      extracted with a mixture of methanol and water and then it was purified by solid
      phase clean-up using a polymeric sorbent, not described previously, for the
      determination of these toxins. The eluted extract was injected into the
      chromatographic system using a reversed-phase C18 short column with an isocratic
      mobile phase composed of methanol-water (30:70). A single-quadruple mass
      spectrometry using an electrospray ionization source operating in the positive
      ion mode was used to detect aflatoxins due to derivatization presenting several
      disadvantages. Recoveries of the full analytical procedure were 110% for
      aflatoxin B1, 89% for aflatoxin B2, 81% for aflatoxin G1 and 77% for aflatoxin
      G2. Detection limit (S/N = 3) was 10 ng and quantification limit (S/N = 10) was
      25 ng, calculated as amount in medicinal herb.

PMID- 15453416
TI  - Hydroxyapatite-based immobilized metal affinity adsorbents for protein
      purification.
AB  - The employment of metal ion-charged hydroxyapatite for the one-step purification
      of poly(His)-tagged recombinant proteins was investigated. Fe(III) showed the
      highest selectivity toward the poly(His)-tagged D-hydantoinase and the best
      operation stability. The optimal selectivity was observed in 20 mM pH 8.0 buffer
      containing 150 mM NaCl and 50 mM NaF. The adsorbed poly(His)-tagged enzyme could
      be quantitatively recovered from hydroxyapatite with 150 mM pH 8.0 phosphate
      buffer. The capacity of Fe(III)-loaded hydroxyapatite for poly(His)-tagged D
      hydantoinase was 4.9 mg/g hydroxyapatite, comparable to commercial agarose-based
      Ni-NTA adsorbents. Under optimal conditions, a D-hydantoinase preparation with a
      purity above 95% from crude cellular lysate could be obtained with the one-step
      purification process employing Fe(III)-loaded hydroxyapatite. The application of
      Fe(III)-loaded hydroxyapatite for the purification of poly(His)-tagged N-acetyl-D
      glucosamine 2-epimerase under denaturing conditions was also demonstrated. These
      results demonstrate that hydroxyapatite is a promising adsorbent for immobilized
      metal affinity chromatography.

PMID- 15453417
TI  - Liquid chromatography-electrospray quadrupole ion-trap mass spectrometry of nine
      pesticides in fruits.
AB  - A liquid chromatographic method, with electrospray ionization tandem mass
      spectrometry (LC-ESI-MS-MS), has been developed for determining acrinathrin,
      carbosulfan, cyproconazole, lambda-cyhalothrin, kresoxim methyl, pyrifenox,
      pyriproxyfen, propanil, and tebufenpyrad in fruits. The ions prominent in ESI
      spectra were [M + H]+ and [M + Na]+. In the mass analyzer, collision-induced
      dissociation fragmentation involved common pathways, for example, product ions of
      [M + H]+ resulted from the cleavage of the carbamic group or an oxygen bound. The
      utility of the method is demonstrated by the analysis of crude extracts obtained
      by matrix solid-phase dispersion (MSPD) using C18 as dispersant and
      dichloromethane-methanol as eluent, and by solid-liquid extraction (SLE) with
      ethyl acetate and anhydrous sodium sulfate. Mean recoveries ranged from 51.5 to
      108%, with relative standard deviations <16%, were obtained for MSPD and from 59
      to 101% with relative standard deviation <17% for SLE. However, for most
      compounds, limits of quantification are better by SLE (0.01-4.4 mg kg(-1)) than
      by MSPD (0.05-2 mg kg(-1)). During the validation process, the procedure was
      tested for matrix effects, blanks and stability of the system. Considerably
      matrix effects in the ESI ionization process were detected by comparing standard
      calibration, and matrix calibration. Because of this, detected residues were
      quantified from interpolation against calibration data obtained using matrix
      matched standards.

PMID- 15453418
TI  - Isolation and purification of inflacoumarin A and licochalcone A from licorice by
      high-speed counter-current chromatography.
AB  - High-speed counter-current chromatography (HSCCC) technique in semi-preparative
      scale has been applied to isolate and purify bioactive flavone compounds from the
      ethanol extract of Glycyrrhiza inflata Bat., a particular plant species of
      licorice. HSCCC separation was performed with a two-phase solvent system composed
      of n-hexane-chloroform-methanol-water (5:6:3:2, v/v) by eluting the lower mobile
      phase at a flow rate of 1.8 ml/min and a revolution speed of 800 rpm.
      Purification was performed with a two-phase solvent system composed of n-hexane
      chloroform-methanol-water (1.5:6:3:2, v/v) by eluting the lower mobile phase at a
      flow-rate of 1.5 ml/min and a revolution speed of 800 rpm. Two major flavone
      peaks: inflacoumarin A and licochalcone A were collected and the respective
      yields of the peaks amount to 6 mg (8.6%, w/w) and 8 mg (11.4%, w/w) from 70 mg
      of the crude extract sample. The purities of inflacoumarin A and licochalcone A
      reached 99.6% and 99.1%, respectively, after a sequential purification run. The
      structures of inflacoumarin A and licochalcone A were positively confirmed by 1H
      NMR and 13C NMR, 1H-13C-COSY, UV, FT-IR and electron ionization MS analyses.

PMID- 15453419
TI  - Efficient method to locate double bond positions in conjugated trienes.
AB  - The double bond positions of 11 conjugated trienes were unambiguously located
      through a simple derivatization method amenable to nanogram-scale analyses. The
      trienes were reacted with the powerful dienophile 4-methyl-1,2,4-triazoline-3,5
      dione (MTAD), and the mass spectra of the resulting cycloadducts exhibited large
      diagnostic fragments which allowed the unequivocal location of the double bonds
      in the parent triene in most cases. Catalytic hydrogenation of the cycloadducts
      produced saturated compounds with characteristic mass spectral fragments from
      which the positions of the trienes in the parent compounds could be readily
      confirmed. Application of the method was demonstrated by the microscale
      identification of two conjugated triene and one conjugated diene components from
      extracts of the sex pheromone gland of the saturniid moth Automeris cecrops
      pamina.

PMID- 15453420
TI  - Development of a static headspace gas chromatographic/mass spectrometric method
      to analyze the level of volatile contaminants biodegradation.
AB  - Volatile compound biodegradation analysis usually requires the time-consuming
      step of extraction of the analytes from the matrix using organic solvents or
      costly radioactive-compounds. Thus, it is desirable to have a simple and fast
      technique to generate a good evaluation of bacterial biodegradation. The goal of
      this research was to develop a methodology on the basis of static headspace-gas
      chromatography/mass spectrometry (HS-GC/MS) to evaluate the level of volatile
      contaminant biodegradation. The effects of the following parameters were studied:
      temperature and time of equilibration. The biodegradation experiments were
      carried out with bacteria inoculation in mineral media in presence of volatile
      hydrocarbon compounds (toluene, p-xylene, nonane and naphthalene). Autoclaved
      inoculates were used as control and reference sample. The optimal headspace
      conditions were observed when the vials were heated at 80 degrees C for 20 min,
      the syringe at 81 degrees C and an injection volume of 0.4 mL was used. This
      methodology has the advantage of being relative free from matrix effects.

PMID- 15453421
TI  - Further solid-phase microextraction-gas chromatography-mass spectrometry
      applications: "on-fibre" and aqueous photodegradation of nitro musks.
AB  - Photodegradation kinetics of four nitro musks (musk xylene, musk tibetene, musk
      ketone and musk moskene) in solid-phase microextraction (SPME) fibres ("photo
      SPME") and in an aqueous system were studied by means of gas chromatography-mass
      spectrometry (MS) detection. Musks fragrances were extracted from aqueous
      solutions using SPME fibres that subsequently were exposed to different UV
      irradiation times, generating photoproducts easily characterized by their mass
      spectra. Aqueous photodegradation studies followed by SPME were also performed
      and compared to photo-SPME. The same fourteen photoproducts have been detected in
      both media. The potential of this approach to readily calculate apparent rate
      constants (from 10(-4) to 10(-3) s(-1)), half-life times (from 3 to 32 min) and
      reaction orders (n = 1) in both media is stated. The main photoreaction
      determined was photocyclization, but products of photoreduction and
      photorearrangement have also been detected. Tentative photodegradation pathways
      for musk moskene and musk tibetene are proposed for the first time.

PMID- 15453422
TI  - Liquid-phase microextraction of tributyltin and triphenyltin coupled with gas
      chromatography-tandem mass spectrometry. Comparison between 4-fluorophenyl and
      ethyl derivatizations.
AB  - This paper describes the liquid-phase microextraction (LPME) of tributyltin (TBT)
      and triphenyltin coupled with gas chromatography-tandem mass spectrometry. The 4
      fluorophenylation and ethylation reactions were used for the derivatization of
      the organotins. For the two derivatizations, the LPME parameters such as organic
      solvent, stirring rate, temperature, extraction time and the other additional
      conditions were examined. Using pure water, the calibration curves, method
      detection limits (MDLs) and reproducibilities (RSDs) of the two derivatizations
      were compared under the respective optimized procedures. The 4-fluorophenyl
      derivatization, which showed a lower MDL (0.36 ng/l) and better reproducibility
      (RSD = 11% at 10 ng/l) for TBT, was applied to the analysis of seawater. The TBT
      was detected in the range from 1.1 to 2.0 ng/l in the seawater samples collected
      in Osaka Bay.

PMID- 15453423
TI  - Liquid-liquid extraction followed by solid-phase extraction for the determination
      of lipophilic pesticides in beeswax by gas chromatography-electron-capture
      detection and matrix-matched calibration.
AB  - Analytical methods for the simultaneous analysis of lindane, chlorpyriphos, z
      chlorfenvinphos, endosulfan A and B, 4,4'-DDE, 4,4'-TDE, acrinathrine,
      bromopropylate, tetradifon, coumaphos and fluvalinate in pure beeswax samples are
      studied. For the analysis of bleached beeswaxes, a liquid-liquid extraction with
      acetonitrile followed by a clean-up on polymeric cartridges is the best option in
      terms of recovery and precision. However, some interferences that hinder the
      identification and quantification of important varroacides are found when non
      bleached beeswaxes are analyzed. The analysis of all compounds in the latter
      samples require a clean-up by coupling an ODS cartridge before the polymeric
      cartridge. Considerations about the influence of the matrix in the quantitative
      analysis by a classical external standard calibration are also made and the use
      of a matrix-matched calibration is advised. Recoveries resulted to be about 100%
      with coefficients of variation between 10% and 20% (n = 5) for concentrations of
      0.5 and 5 mg/kg.

PMID- 15453424
TI  - Retention characteristics of porous graphitic carbon in subcritical fluid
      chromatography with carbon dioxide-methanol mobile phases.
AB  - Numerous relationships usually used in high-performance liquid chromatography
      (HPLC) for describing the retention on porous graphitic carbon (PGC) have been
      applied in subcritical fluid chromatography, with CO2-methanol mobile phases. As
      reported in HPLC, octanol-water partition coefficient failed to fit the
      retention, whereas satisfactory results were obtained with the sum of partial
      negative charges. A better fit was reached by using the solvation parameter
      model, allowing a better understanding of the interactions developed between the
      solute, the stationary and the mobile phases. Results show that the dominant
      contribution to retention was given by the polarizability (E) and the volume (V),
      while the hydrogen-bond basicity (B) was not selected in the retention model,
      whatever the methanol content. The increase in methanol percentage favours the
      retention decrease, mainly through the volume for hydrophobic compounds, and
      through the hydrogen-bond acidity for polar compounds.

PMID- 15453425
TI  - Chiral separation of bupivacaine enantiomers by capillary electrophoresis partial
      filling technique with human serum albumin as chiral selector.
AB  - Capillary electrophoresis (CE) is a powerful technique for enantiomer separations
      due to its intrinsic high separation efficiencies, speed of analysis, low reagent
      consumption and small sample requirements. However, some chiral selectors present
      strong background UV absorption providing high detection limits. The present
      paper deals with the application of the partial-filling technique to the
      separation of bupivacaine enantiomers by capillary electrophoresis using human
      serum albumin (HSA) as chiral selector. In this procedure the cationic surfactant
      cetyltrimethylammonium bromide (CTAB) was used as a dinamic capillary coating in
      order to reduce the electro-osmotic flow and detect both bupivacaine enantiomers
      out of the chiral selector plug. Several experimental conditions such as CTAB
      concentration, pH, HSA concentration and plug length, background electrolyte
      concentration, temperature and voltage were studied. Under the selected
      conditions it is possible to detect the separated enantiomers out of the HSA plug
      in less than 4 min using 50 mM Tris pH 8 as background electrolyte with 50 microM
      CTAB, at 30 degrees C and using a separation voltage of 25 kV. The proposed
      methodology was then validated for analytical purposes and applied to the
      analysis of pharmaceutical preparations commercially available. The results
      obtained with the proposed methodology were in good agreement with those declared
      by the manufacturers. The simplicity, sample throughput, accuracy,
      reproducibility and low cost of the proposed method make it suitable for the
      control of the enantiomeric composition of bupivacaine in pharmaceuticals.

PMID- 15453426
TI  - Analysis of some cytokinins in coconut (Cocos nucifera L.) water by micellar
      electrokinetic capillary chromatography after solid-phase extraction.
AB  - Micellar electrokinetic capillary chromatography (MECC) was developed for the
      separation of cytokinins including trans-zeatin, trans-zeatin-O-glucoside,
      dihydrozeatin, dihydrozeatin-O-glucoside, meta-topolin riboside, N6
      isopentenyladenine and N6-benzylaminopurine. Under the optimum conditions, i.e. a
      combination of 10 mM phosphate and 10 mM borate as the running buffer containing
      50 mM sodium dodecyl sulphate at pH 10.4, the separation of seven cytokinin
      standards was accomplished within 11 min. The C18 solid-phase extraction (SPE)
      method was used to pre-concentrate the putative cytokinins present in the coconut
      water. Following which, the eluate was further purified using mixed mode Oasis
      MCX SPE columns and this additional step helps to reduce matrix interference
      during MECC. After the two solid-phase extraction steps, the optimized MECC
      method was able to screen for certain cytokinins (zeatin-O-glucoside and
      dihydrozeatin-O-glucoside) present in coconut water. After this screening, the
      presence of zeatin-O-glucoside and dihydrozeatin-O-glucoside in coconut water was
      further confirmed by independent high-performance liquid chromatography and
      liquid chromatography-mass spectrometry experiments.

PMID- 15453427
TI  - Cationic vesicles as chiral selector for enantioseparations of nonsteroidal
      antiinflammatory drugs by micellar electrokinetic chromatography.
AB  - A vesicle-forming chiral cationic surfactant (1R,2S)-(-)-N-dodecyl-N-methyl
      ephedrinium bromide was evaluated as a pseudo-stationary phase in micellar
      electrokinetic chromatography (MEKC) for enantioseparation of eight non-steroidal
      anti-inflammatory drugs e.g., carprofen, flurbiprofen, fenoprofen, ibuprofen,
      indoprofen, ketoprofen, naproxen and suprofen by capillary electrophoresis. The
      effects of varying experimental conditions such as pH and concentration of
      surfactant in the running buffer on the enantiomer separation of the drugs are
      reported. A mixture of five of the above drugs was separated and each
      enantiomeric pair was also separated simultaneously in a single run by use of the
      surfactant. The strong electrostatic interactions between the analytes and the
      vesicles seemed to have a major role in the enantiomeric separation of the
      profens.

PMID- 15453428
TI  - Determination of methyl tert-butyl ether in gasoline: a comparison of three fast
      methods based on mass spectrometry.
AB  - A high-speed quantitative analysis of methyl tert-butyl ether (MTBE) using three
      different methods with mass spectrometry detection has been performed. The first
      method is based on fast chromatography and required an analysis time of 5.23 min
      per sample, although a certain period (6 min) was necessary for the initial
      measurement conditions to be regained prior to analysing the next sample. The
      other two are non-separative methods and are based on direct injection and
      headspace generation. The analysis times were 1.5 and 3.5 min, respectively,
      although in the latter case an additional period of time was required to extract
      volatiles from the sample. The analytical characteristics of all three methods
      are highly satisfactory in terms of linearity, lack of fit, precision and
      accuracy. The methods were applied to the determination of MTBE in different
      gasoline samples. The non-separative methods afforded slightly higher
      concentrations than those found when fast chromatography was used; this is due to
      the presence of other minor components that contribute to the abundance of the
      ion at m/z 73, characteristic of MTBE. We propose a correction that removes this
      error very satisfactorily and allows the same results to be obtained with all
      three methodologies proposed.

PMID- 15453429
TI  - [Geriatrics and internal medicine].

PMID- 15453430
TI  - [What is your diagnosis? Tachycardia with wide QRS complexes].

PMID- 15453431
TI  - [Fall risk factors and fall injuries in hospitalized elderly patients].
AB  - Fall Risk Factors have been analysed (RAI-MDS-System) in a population of
      patients, who were hospitalised between 1995 and 2000 in a geriatric department
      of a community hospital. In multivariate analysis, viseral-problems, incontinence
      and depression were fall-protective factors, whereas problems with transfer, the
      use of assistive walking-aids, female gender and age were fall risk-factors. No
      independent contribution to the fall-risk was delivered by memory-impairment,
      problems in decision-making, low body-mass-index, the use of more than three
      medications and the use of restraints. Fall injuries were analysed in a patient
      population (n = 218), that was hospitalized in the year 2001 in the geriatric
      department of a community hospital after a fall. The analysis showed an enormous
      heterogenicity of the injury-patterns: 58.7% of the fall-patients suffered from a
      fracture, 10.6% of them had more than one fracture, 34% suffered from other
      injuries. 77 surgical interventions were performed. The mean length of stay of
      the fall-patients was 4.5 days higher than the mean of all geriatric patients.

PMID- 15453432
TI  - [Sensible anticancer treatment in the very old].
AB  - Significant numerical increase of elderly people augments in parallel the number
      of geriatric oncological situations. It is thus necessary to bridge between two
      apparently divergent worlds. This will allow to look at and evaluate the elderly
      cancer person with the accuracy of the specialist while remaining at the
      appropriate distance ordered by the geriatrician eye. It becomes then possible to
      undertake diagnostic and therapeutic manoeuvres in the respect of everybody's
      individuality. This contributes to maintain the best quality of life possible
      until the end. Pater(mater)nalism is to be abandoned and knowledge is to be
      shared. Daily interdisciplinarity, humanitarian spirit and ethical sensibility
      are essentials tools to make this enterprise a success.

PMID- 15453433
TI  - [Infections in the elderly].
AB  - Demographic aging is now well established. Thus, infections in the elderly will
      continue to become an increasingly important public health issue. Infections are
      not only more frequent in the elderly, but they also have distinct properties.
      Infectious diseases of the elderly are distinct with respect to epidemiology,
      clinical presentation, treatment, and outcome. Theses specificities are explained
      through a variety of factors, including the ageing process itself, but also
      comorbidities, sociological and environmental factors. Geriatric infectious
      diseases is likely to develop as an increasingly important branch of geriatrics
      and infectious disease.

PMID- 15453434
TI  - [Pharmacokinetics and pharmacodynamices in the elderly].
AB  - Pharmacokinetic and dynamic alterations, the appearance of multiple illnesses
      which are treated with polypharmacy and, possibly as a consequence of
      polypharmacy, impaired compliance with drug therapy are associated with a higher
      incidence of drug-drug interactions and adverse drug reactions in geriatric
      patients. The most important among these alterations are discussed and possible
      solutions are presented.

PMID- 15453435
TI  - [Diagnosis and treatment of vascular dementia].
AB  - Vascular dementia is the second cause of dementia after Alzheimer's disease. It
      is a broad term which includes dementia due to: single or multiple infarcts
      related to large vessel disease, subcortical ischemic pathology linked to small
      vessel disease, hemorrhages, and hypoperfusion. Furthermore, vascular and
      Alzheimer lesions often coexist leading to a mixed dementia. The diagnosis should
      be considered in the presence of dementia, clinical or neuroradiological signs of
      cerebrovascular disease and a plausible link between the two. Newly identified
      preventive strategies and encouraging results of recent trials using
      cholinesterase inhibitors or memantine suggest therapeutic potential.

PMID- 15453436
TI  - [Renal replacement therapy in octogenarians].

PMID- 15453437
TI  - [Erection help from the rain forest?].

PMID- 15453438
TI  - [Told story (stories): brain death from the viewpoint of the actors].

PMID- 15453439
TI  - Single- or multiple-tooth implant restoration on the same arch.

PMID- 15453440
TI  - Ways to recover from work-induced stress.
AB  - For most health professionals, stress goes with the job. It is also a factor for
      many clients and families. This article explains recent thinking on recovery from
      work-related stress and outlines some everyday strategies to help.

PMID- 15453441
TI  - Value children, value child care.
AB  - Evidence suggests that quality child care is good for children, good for parents
      and good for society, but there is a shortage of day-care places and not all
      parents who want one can afford it. The workforce who undertake the day care of
      young children deserve greater recognition for what they do and should be well
      trained and well rewarded.

PMID- 15453442
TI  - Newborn screening for medium chain acyl-CoA dehydrogenase deficiency (MCADD) in
      the UK.
AB  - The Department of Health and the National Screening Committee are funding a new
      newborn screening service for the rare inherited disorder medium chain acyl-CoA
      dehydrogenase deficiency, otherwise known as MCADD. Screening commenced as a
      pilot programme on 1 March 2004 from six laboratories in England. An evaluation
      study following all positive cases of MCADD from this first two-year pilot period
      will continue for a further three years to measure the overall effectiveness of
      screening for MCADD in the UK. This article reviews the background to the
      introduction of the pilot programme and describes the features and complications
      of MCADD, including the diagnosis and management.

PMID- 15453443
TI  - What do we know about... diabetes and obesity in adults and children?
AB  - The increased incidence of diabetes is linked with the rising incidence of
      obesity in adults and children in the UK. The National Framework for diabetes has
      identified obesity as the most significantly modifiable risk factor for type 2
      diabetes. In this article, two specialist dietitians and a specialist nurse
      discuss exercise and diet in the prevention and management of diabetes in adults
      and children, with particular reference to obesity and type 2 diabetes.

PMID- 15453444
TI  - Children with special needs--1: What choices do parents have?
AB  - In the first of two articles, a health visitor for special needs children
      discusses the limitations of choices open to parents of a child with
      disabilities. Both the child and the family often suffer restricted opportunities
      and rigid attitudes from health and education authorities. Provision of care is
      often a lottery. The author outlines new policies for improving choice, taking
      parents' wishes into account and providing more co-ordinated services.

PMID- 15453445
TI  - Liberating the talents: school nurses, the sexual health agenda and the future.

PMID- 15453447
TI  - The future of CDHPs: the only thing constant is change?

PMID- 15453446
TI  - Desire to expand, launch clinics outpaces federal funding.

PMID- 15453448
TI  - [Thermoregulation in Chiroptera].

PMID- 15453449
TI  - [Homeostasis of sodium and potassium ions in lamprey Lampetra fluviatilis:
      influence ion transport and metabolic blockers and ionophores. ].

PMID- 15453450
TI  - [Comparative study of substate-inhibitory specificity of brain cholinesterase of
      Pacific Salmonidae].

PMID- 15453451
TI  - [Temperature and pH influence on proteinases activity of fish intestinal mucose
      and enteric microflora].

PMID- 15453452
TI  - [Differential involvement of central l-glutamate receptors of non-NMDA subtype in
      associative training honey bee Apis mellifera. ].

PMID- 15453453
TI  - [Hypothermal effects of physiology of honey bee Apis mellifera queens].

PMID- 15453454
TI  - [Influence of NO-synthase inhibitors on embryonal development of sea urchins].

PMID- 15453455
TI  - [Influence of small doses of thyroliberin and vasopressin on memory processes of
      European hedgehog Erinaceus europaeus ( Insectivora, Erinaceidae)].

PMID- 15453456
TI  - [Characteristics of visceral and somatomotoric interactions in young rats during
      changes of adrenergic structures activity. ].

PMID- 15453457
TI  - [Conditional reflexive reaction of passive avoidance of rat males and females
      exposed to hypoxia during different stages of prenatal development].

PMID- 15453458
TI  - [Blood supply of organs during rest in rodents with different body weight].

PMID- 15453459
TI  - [The study of relaxation mechanisms in blood vessels differ in density and type
      of innervation in rats].

PMID- 15453460
TI  - [Otolithic membrane evolution. Otolithic membrane structure in amphibia and
      reptiles. ].

PMID- 15453461
TI  - [Age dynamic of body weight and longevity oh human life].

PMID- 15453462
TI  - [Monoclonal antibody detection of Coelenterata and Echinodermata antigens].

PMID- 15453464
TI  - IMRT bundling myths.
AB  - Payment for IMRT planning bundles, or includes, many services represented by
      other procedure codes when performed on the same date. As a result, radiation
      therapy providers must maintain an awareness of bundling edits and coding
      guidelines to ensure complete and accurate reimbursement for this advanced
      technology.

PMID- 15453465
TI  - Promoting high-quality comprehensive cancer care.

PMID- 15453466
TI  - Strategic planning--implementation planning.

PMID- 15453467
TI  - Supporting research in nursing leads to evaluation tool for cerebellar toxicity.
AB  - Evidenced-based practice allows nurses to provide quality patient care while
      meeting the increasing demands of today's healthcare environment. Transitioning
      nurses to an evidence-based practice requires administrative support, education,
      collaboration, and a willingness to change from all levels of healthcare
      providers as shown in an example from a Midwestern community medical center.

PMID- 15453468
TI  - Investing in the future: mentoring next generation leaders.
AB  - The American Academy of Medical Administrators of Tennessee (AAMA-TN) Chapter has
      established a graduate level internship program for individuals interested in a
      career in health care management. One such internship included involvement in a
      variety of programs such as Cancer Answer Evenings, National Cancer Survivor Day,
      community-wide skin cancer screenings, and submission of an R-25 Federal Grant,
      the Tennessee Comprehensive Cancer Control Plan.

PMID- 15453469
TI  - Letter to the editor: management of bacterial burden in cattle by TiO2 from
      grazing.

PMID- 15453470
TI  - Physicochemical and kinetic properties of purified sheep's milk xanthine
      oxidoreductase.
AB  - Xanthine oxidoreductase (XOR) was purified for the first time from sheep's milk.
      The ultraviolet-visible absorption spectrum was essentially identical to those of
      the corresponding bovine, human, and goats' milk enzymes and showed an A280/A450
      ratio of 5.35 +/- 0.24, indicating a high degree of purity. Like milk XOR from
      other species, sheep's milk enzyme showed a single band on SDS-PAGE corresponding
      to a subunit with approximate Mr 150,000. Xanthine oxidase activity of purified
      sheep's milk XOR (0.69 +/- 0.04 micromole urate min(-1) mg(-1)) was low relative
      to that of the bovine milk enzyme (1.83 +/- 0.02 micromole urate min(-1) mg(-1)),
      but higher than those of human or goats' milk XOR. As in the latter 2 cases, the
      low activity of sheep's milk XOR can be attributed to its relatively low
      molybdenum content (0.18 atoms per subunit), compared with that of the bovine
      milk enzyme (0.56 atoms Mo per subunit). Consistent with this, NADH oxidase
      activity of sheep's milk XOR was similar to that of enzymes purified from bovine,
      human, or goats' milk. The presence of desulpho-enzyme in sheep's milk XOR was
      demonstrated by resulfuration experiments, whereby xanthine oxidase activity was
      increased by approximately 75%.

PMID- 15453471
TI  - Impact of autolytic, proteolytic, and nisin-producing adjunct cultures on
      biochemical and textural properties of cheddar cheese.
AB  - The effect of incorporating a highly autolytic strain (Lactobacillus delbrueckii
      subsp. bulgaricus UL12) a proteolytic strain (Lactobacillus casei subsp. casei
      L2A), or a nisin Z-producing strain (Lactococcus lactis, subsp. lactis biovar
      diacetylactis UL719) into Cheddar cheese starter culture (Lactococcus lactis KB
      and Lactococcus cremoris KB) on physicochemical and rheological properties of the
      resultant cheeses was examined. Cheeses were ripened at 7 degrees C and analyzed
      over a 6-mo period for viable lactococcal and lactobacilli counts, pH, titratable
      acidity (TA), lipolysis, proteolysis, and textural characteristics. The
      combination of the nisin-producing strain and autolytic adjuncts significantly
      increased the production of water-soluble nitrogen, free amino acids, and free
      fatty acids. The effect of Lc. diacetylactis UL719 alone or of Lb. casei L2A on
      water-soluble nitrogen and free amino acid contents were also significant,
      whereas their effect on free fatty acids was not. Viable counts of Lb. bulgaricus
      UL12 were significantly reduced in the presence of Lc. diacetylactis UL719.
      Lactobacilli-containing cheeses showed significantly lower values for hardness,
      fracturability, and springiness. It could be concluded that the addition of Lb.
      bulgaricus UL12 together with a nisin-producing strain produces a greater
      increase in cheese proteolysis and an improvement in Cheddar cheese texture.

PMID- 15453472
TI  - Detection of milk mixtures in Halloumi cheese.
AB  - A capillary electrophoresis method has been applied to the detection of illegal
      addition of milk from goat and/ or cow in Halloumi cheese, traditionally made
      with sheep milk. The electrophoretic profiles of the casein from Halloumi cheeses
      have revealed that caprine para-kappa-casein and bovine alphas1-casein peaks
      point to the presence of low percentages of goat's and/or cow's milk added to
      Halloumi cheese. Stepwise multiple linear regression has been used to predict
      these percentages with a standard error of the estimation of 2.14%. The
      analytical method combined with the statistical application is valid for the
      prediction of percentages higher than 2% of goat's and percentages of 5% of cow's
      milk added to the cheese either in fresh or ripened cheese. The standard error of
      estimation was higher for the prediction of cow's milk than for goat's milk.

PMID- 15453473
TI  - Sensory shelf life of dulce de leche.
AB  - The objectives of this research were to determine the sensory cutoff points for
      dulce de leche (DL) critical descriptors, both for defective off-flavors and for
      storage changes in desirable attributes, and to estimate the shelf life of DL as
      a function of storage temperature. The critical descriptors used to determine the
      cutoff points were plastic flavor, burnt flavor, dark color, and spreadability.
      Linear correlations between sensory acceptability and trained panel scores were
      used to determine the sensory failure cutoff point for each descriptor. To
      estimate shelf life, DL samples were stored at 25, 37, and 45 degrees C. Plastic
      flavor was the first descriptor to reach its cutoff point at 25 degrees C and was
      used for shelf-life calculations. Plastic flavor vs. storage time followed zero
      order reaction rate. Shelf-life estimations at different temperatures were 109 d
      at 25 degrees C, 53 d at 37 degrees C, and 9 d at 45 degrees C. The activation
      energy, necessary to calculate shelf lives at different temperatures, was 14,370
      +/- 2080 cal/mol.

PMID- 15453474
TI  - Hydrolysis of lactose in whey permeate for subsequent fermentation to ethanol.
AB  - Fermentation of lactose in whey permeate directly into ethanol has had only
      limited commercial success, as the yields and alcohol tolerances of the organisms
      capable of directly fermenting lactose are low. This study proposes an
      alternative strategy: treat the permeate with acid to liberate monomeric sugars
      that are readily fermented into ethanol. We identified optimum hydrolysis
      conditions that yield mostly monomeric sugars and limit formation of fermentation
      inhibitors such as hydroxymethyl furfural by caramelization reactions. Both
      lactose solutions and commercial whey permeates were hydrolyzed using inorganic
      acids and carbonic acid. In all cases, more glucose was consumed by secondary
      reactions than galactose. Galactose was recovered in approximately stoichiometric
      proportions. Whey permeate has substantial buffering capacity-even at high
      partial pressures (>5500 kPa[g]), carbon dioxide had little effect on the pH in
      whey permeate solutions. The elevated temperatures required for hydrolysis with
      CO2-generated inhibitory compounds through caramelization reactions. For these
      reasons, carbon dioxide was not a feasible acidulant. With mineral acids
      reversion reactions dominated, resulting in a stable amount of glucose released.
      However, the Maillard browning reactions also appeared to be involved. By
      applying Hammet's acidity function, kinetic data from all experiments were
      described by a single line. With concentrated inorganic acids, low reaction
      temperatures allowed lactose hydrolysis with minimal by-product formation and
      generated a hexose-rich solution amenable to fermentation.

PMID- 15453475
TI  - Antibacterial activity of lactophoricin, a synthetic 23-residues peptide derived
      from the sequence of bovine milk component-3 of proteose peptone.
AB  - A synthetic peptide of 23 residues corresponding to the carboxyterminal 113 to
      135 region of component-3 of proteose peptone (PP3) has been investigated with
      regard to its antibacterial properties. This cationic amphipathic peptide that we
      refer to as lactophoricin, displayed a growth-inhibitory activity against both
      gram-positive and gram-negative bacteria. For most of the strains tested,
      bacterial growth was observed in the presence of lactophoricin except for
      Streptococcus thermophilus. In that case, lactophoricin exhibited a minimum
      inhibitory concentration of 10 microM and a minimum lethal concentration of 20
      microM. No hemolysis of human red blood cells was detected for peptide
      concentrations between 2 to 200 microM, indicating that lactophoricin would be
      noncytotoxic when used in this concentration range.

PMID- 15453476
TI  - Partial characterization of dextran-degrading enzyme obtained from blue cheese.
AB  - Degradation of dextran beads was observed when the water-soluble fraction of a
      blue cheese extract was applied to the top of a Sephadex G-150 or G-200 column.
      This phenomenon suggests the presence of a specific enzyme that can hydrolyze
      dextran. After removal of casein components from the blue cheese fraction,
      ammonium sulfate treatment and gel filtration chromatography were performed to
      isolate the enzyme fraction. The enzymatic products were analyzed by thin-layer
      chromatography and gel filtration chromatography and identified as
      isomaltooligosaccharides. The isoelectric point of this enzyme fraction was
      approximately 4.9, as determined by isoelectric focusing using Rotofor, and the
      molecular weight of the fraction was 65 kDa, as estimated by sodium dodecyl
      sulfate (SDS)-PAGE. Optimum pH for enzymatic activity was 5.0 to 5.3. A partial N
      terminal amino acid sequence of 20 residues was determined to be
      ATPDEWRSRSIYFMLTDRGA from an enzyme fraction further purified by ion-exchange
      chromatography and native PAGE. This sequence showed a maximum homology of 80%
      with alpha-amylase or Taka amylase that originated from various microorganisms.

PMID- 15453477
TI  - Selection and properties of Streptococcus thermophilus mutants deficient in
      urease.
AB  - Natural variations of the urea content of milk have a detrimental effect on the
      regularity of acidification by Streptococcus thermophilus strains used in dairy
      processes. The aim of the present study was to select urease-deficient mutants of
      S. thermophilus and to investigate their properties. Using an improved screening
      medium on agar plates, mutants were selected from 4 different parent strains
      after mutagen treatment and by spontaneous mutation. Most mutants were stable and
      had a phage sensitivity profile similar to that of their parent strain. Some of
      them contained detrimental secondary mutations, as their acidifying activity was
      lower than that of the parent strain cultivated in the presence of the urease
      inhibitor flurofamide. The proportion of this type of mutant was much lower among
      spontaneous mutants than among mutants selected after mutagen treatment.
      Utilization of urease-deficient mutants in dairy processes may have several
      advantages, such as an increase in acidification, an improved regularity of
      acidification, and a lower production of ammonia in whey.

PMID- 15453478
TI  - Nomenclature of the proteins of cows' milk--sixth revision.
AB  - This report of the American Dairy Science Association Committee on the
      Nomenclature, Classification, and Methodology of Milk Proteins reviews changes in
      the nomenclature of milk proteins necessitated by recent advances of our
      knowledge of milk proteins. Identification of major caseins and whey proteins
      continues to be based upon their primary structures. Nomenclature of the
      immunoglobulins consistent with new international standards has been developed,
      and all bovine immunoglobulins have been characterized at the molecular level.
      Other significant findings related to nomenclature and protein methodology are
      elucidation of several new genetic variants of the major milk proteins,
      establishment by sequencing techniques and sequence alignment of the bovine
      caseins and whey proteins as the reference point for the nomenclature of all
      homologous milk proteins, completion of crystallographic studies for major whey
      proteins, and advances in the study of lactoferrin, allowing it to be added to
      the list of fully characterized milk proteins.

PMID- 15453479
TI  - Effect of milking pipeline height on machine milking efficiency and milk quality
      in sheep.
AB  - This experiment studied the effect of milking pipeline height (mid- vs. low-level
      milking system) on milking efficiency and milk composition. The experiment was of
      8 wk duration: 2 wk preexperimental period and 6 wk experimental, in crossover
      design (2 x 2). Ewes were milked in a 2 x 12 milking parlor with 2 milking
      pipelines set at a milking vacuum of 36 kPa with a pulsation rate of 180
      cycle/min and ratio of 50%. Height of the milkline had no effect on yield of milk
      at the time of milking, yield after stripping, milk composition, SCC, and number
      of teatcup fall-offs. Nor did milkline height have any effect on milk lipolysis
      or on the distribution of fatty acids. The level of free fatty acids was higher
      in evening than in morning milk (60.5 vs. 25.6 mg/L). Likewise, the increase in
      the degree of lipolysis between the receiver (40.4 mg/L) and the refrigeration
      tank (45.8 mg/L) underlines the importance of the milk delivery line design. The
      parameters (time and flow rate) that define the first peak in the milk emission
      kinetics were statistically different between lines, so care must be taken when
      comparing milk emission curves from both types of pipeline.

PMID- 15453480
TI  - Hormonal and lactational responses to growth hormone-releasing hormone treatment
      in lactating Japanese Black cows.
AB  - Ten multiparous lactating Japanese Black cows (beef breed) were used to evaluate
      the effects of bovine growth hormone-releasing hormone (GHRH) analog on milk
      yield and profiles of plasma hormones and metabolites. The cows received 2
      consecutive 21-d treatments (a daily s.c. injection of 3-mg GHRH analog or
      saline) in a 2 (group) x 2 (period) Latin square crossover design. The 5 cows in
      group A received GHRH analog during period 1 (from d 22 to 42 postpartum) and
      saline during period 2 (from d 57 to 77 postpartum), and those in group B
      received saline and GHRH analog during periods 1 and 2, respectively. Mean milk
      yield decreased in saline treated compared with that during the 1-wk period
      before treatment 7.4 and 19.1% during periods 1 (group B) and 2 (group A),
      respectively. Treatment with GHRH analog increased milk yield 17.4% (period 1,
      group A) and 6.3% (period 2, group B). Treatment with GHRH analog induced higher
      basal plasma concentrations of growth hormone (GH), insulin-like growth factor-1
      (IGF-1), insulin, and glucose compared with saline-treated cows. In glucose
      challenge, the GHRH analog-treated beef cows had greater insulin secretion than
      the saline-treated beef cows. In insulin challenge, however, there were no
      significant differences in the areas surrounded by hypothetical lines of basal
      glucose concentrations and glucose response curves between GHRH analog- and
      saline-treated cows. These results demonstrate that GHRH analog treatment
      facilitates endogenous GH secretion in lactating Japanese Black cows, leading to
      increases in milk yield and plasma concentrations of IGF-1, insulin, and glucose.

PMID- 15453481
TI  - Bacterial populations on teat ends of dairy cows housed in free stalls and bedded
      with either sand or sawdust.
AB  - The main objectives of the experiment were: 1) to compare bacterial populations
      of mastitis-causing organisms on the teats of lactating dairy cattle housed on
      sand and sawdust bedding and, 2) to examine the relationship between bacterial
      counts present in the 2 bedding types with those on teat ends. Sixteen lactating
      Holstein cows were housed on either sand or sawdust-bedded free stalls using a
      crossover design with 3 wk per bedding type. Bedding samples were collected on d
      0 (prior to animals lying on the bedding), 1, 2, and 6. Teat ends were sampled
      prior to the morning milking on d 1, 2, and 6. All samples were analyzed to
      determine coliform, Klebsiella spp., and Streptococcus spp. populations. There
      were 2 times more coliforms and 6 times more Klebsiella bacteria on teat ends of
      cows housed on sawdust compared with those housed on sand. In contrast, there
      were 10 times more Streptococcus spp. bacteria on teat ends of cows when housed
      on sand compared with sawdust. In both sawdust and sand bedding, coliforms,
      Klebsiella and Streptococcus counts increased over each experimental week,
      although patterns varied with bedding and bacteria type. Bacterial counts on teat
      ends were correlated with bacterial counts in sawdust (r = 0.47, 0.69, and 0.60
      for coliforms, Klebsiella spp., and streptococci, respectively) and in sand (r =
      0.35 for coliforms and r = 0.40 for Klebsiella spp.). In conclusion, coliforms
      and Klebsiella spp. on teat ends were more numerous when cows were housed on
      sawdust bedding, but Streptococcus spp. were more numerous on teat ends of cows
      housed on sand.

PMID- 15453482
TI  - Automatic milking and grazing--effects of distance to pasture and level of
      supplements on milk yield and cow behavior.
AB  - In an automatic milking system, 45 cows were divided into groups that grazed on a
      mixed grass sward (Poa Pratensis and Festuca Pratensis) at different distances
      from the barn: near pasture (NP) at 50 m between the barn and the pasture and
      distant pasture (DP) at 260 m between the barn and the pasture. For both of these
      treatments, 3 kg of dry matter (DM) from supplementary grass silage were offered
      in the barn. The third treatment group grazed together under the DP treatment but
      was offered an ad libitum supply of grass silage in the barn (DP + S). Cows were
      also fed concentrates in relation to requirements (average 7 kg/d per cow).
      During the period from June 5 to July 13 (Period 1), cows in the NP group had a
      higher milk yield (29.1 kg) than did cows in the DP group (26.4 kg) and had a
      higher milking frequency compared with the other groups, 2.5 vs. 2.3 and 2.3
      milkings/d, respectively. During August, cows in group DP + S had a lower milking
      frequency (2.1 milkings/d) compared with the two groups on lower supplementation
      (2.5 milkings/d). In Period 1, all groups spent approximately 20% of their time
      grazing, but after mid July groups DP and DP + S decreased the time they spent
      grazing to around 10%; cows in group NP continued to graze as before. Thus,
      longer distances to pasture may lead to decreases in milk yield, milking
      frequency, and grazing time of cows in an automatic milking system. The higher
      level of silage supplementation (group DP + S) did not result in a significantly
      higher milk yield compared with herd-mates (DP) also grazing the more distant
      pasture.

PMID- 15453483
TI  - Cortisol in saliva and plasma of cattle after ACTH administration and milking.
AB  - Interest in the measurement of salivary cortisol has increased recently because
      saliva can be easily collected before and after an imposed stress. This study
      evaluated the relationship between plasma and salivary concentrations of cortisol
      following ACTH administration in calves (experiment 1) and machine milking of
      adult cows (experiment 2). A catheter was inserted into the jugular vein of all
      animals 72 h before the beginning of experiments. Blood and saliva samples were
      collected before and after ACTH administration (0.6 IU/kg BW) in calves or before
      and after machine milking of cows. Using a cotton swab, each saliva sample was
      taken immediately following the blood sample. In general, cortisol profiles were
      similar in plasma and saliva and correlated in both experiments; however, plasma
      concentrations were significantly higher than salivary concentrations. In
      addition, the differences between cortisol concentrations measured in saliva and
      plasma within each experiment varied substantially between animals and samples.
      Furthermore, in experiment 2, nearly 10% of salivary samples were below limits of
      detection. The sharp peaks in cortisol after ACTH administration in both the
      plasma and saliva were reflected adrenal stimulation. In addition, increases in
      cortisol in response to milking in both the plasma and saliva suggest that
      salivary sampling is a reliable option when studying cortisol responses to normal
      physiological events.

PMID- 15453484
TI  - Changes in milk composition as affected by subclinical mastitis in goats.
AB  - The mechanism of the effects of subclinical mastitis (SM) at the glandular level
      in dairy goats on milk yield and its composition as expressed in curd yield (Yc)
      was studied. Twenty-five Israeli goats of various crossbreeds were chosen; one
      udder half was naturally infected with identified coagulase-negative
      staphylococci, and the contralateral gland was free of bacteria. The milk yield
      of the infected halves was significantly lower than that of the uninfected ones.
      Somatic cell count and N-acetyl-beta-D-glucosaminidase activity were
      significantly higher in the infected halves. The lactose concentration in the
      infected glands was significantly lower than that in the uninfected ones, casein
      concentrations did not differ, and the whey protein and albumin concentrations
      were significantly higher in the infected glands. Plasmin activity was
      significantly higher in the infected glands, whereas plasminogen activity was
      undetectable. Concentrations of Ca2+ did not differ, whereas Ca2+ activity was
      significantly lower in the infected glands. The proteose peptone concentration
      was 1.5 times as great in the infected glands as in the uninfected ones. The Yc
      was significantly lower in the infected halves, and clotting time was
      significantly longer. The mechanisms of the effects of SM on milk yield and Yc in
      goats and sheep are discussed and compared.

PMID- 15453485
TI  - Influence of prepartum pirlimycin hydrochloride or penicillin-novobiocin therapy
      on mastitis in heifers during early lactation.
AB  - A study was conducted in 2 dairy research herds to determine whether prepartum
      therapy of heifer mammary glands with penicillin-novobiocin or pirlimycin
      hydrochloride was effective for reducing the percentage of heifers and mammary
      quarters infected with mastitis pathogens during early lactation. Almost 96% of
      Jersey heifers (67 of 70) and 71.3% of quarters (199 of 279) were infected 14 d
      before expected calving. Of the quarters infected at 14 d before expected
      parturition, 75% (54 of 72) were uninfected following treatment with penicillin
      novobiocin; 87% (61 of 70) were uninfected following treatment with pirlimycin,
      and 56% (32 of 57) were uninfected in the untreated negative control group. The
      majority of intramammary infections in Jersey heifers were due to coagulase
      negative staphylococci (61%), Streptococcus species, primarily Streptococcus
      uberis (19%), and Staphylococcus aureus (8%). Almost 73% of Holstein heifers (40
      of 55) and 34.3% of mammary quarters (73 of 213) were infected 14 d before
      expected calving. Of the quarters infected at 14 d before expected parturition,
      76% (19 of 25) were uninfected following treatment with penicillin-novobiocin;
      59% (17 of 29) were uninfected following treatment with pirlimycin, and 26% (5 of
      19) were uninfected in the untreated negative control group. The majority of
      intramammary infections in Holstein heifers were due to coagulase-negative
      staphylococci (44%) and Staph. aureus (30%). In both herds, the bacteriological
      cure rate was significantly higher in heifer mammary glands treated with
      penicillin-novobiocin or pirlimycin hydrochloride than in untreated controls.
      Prepartum therapy of heifer mammary glands with penicillin-novobiocin or
      pirlimycin hydrochloride significantly reduced the percentage of heifers and
      quarters infected with mastitis pathogens during early lactation.

PMID- 15453486
TI  - The effect of preventive trimming on weight bearing and force balance on the
      claws of dairy cattle.
AB  - Claw disorders and lameness in dairy cattle are an increasing problem of the
      modern dairy industry. To prevent claw disorders from evolving from the
      subclinical to the clinical stage, trimming is the management practice most
      routinely applied. The goal of preventive trimming (Toussaint-Raven method) is to
      promote natural loading by increasing the weight-bearing contact area of the
      claws and improving the balance between the medial and lateral claw. The
      biomechanical effect of preventive claw trimming was investigated with the aid of
      pressure distribution and ground reaction force recordings of the standing cow
      sampled simultaneously at 250 Hz. It appeared that preventive trimming of the
      hind limbs (n = 10) brought the claws slightly more in balance. Before trimming,
      80% of the total force is taken up by the lateral claw and 20% by the medial
      claw. After trimming, this becomes 70 to 30%, respectively. Thereby, a
      significant increase in the weight-bearing contact area from 27.5 to 40.0 cm2 was
      achieved, resulting in a significant decrease in average pressure. However, the
      claws remained subjected to unaltered, high maximum pressures after trimming. The
      suggestion was made that the main focus of claw trimming should not be force
      balance; instead, a reduction of local maximum pressures at the contact area
      should be targeted in such a way that the strongest parts of the claw capsule
      (i.e., the wall) will be subjected to the highest pressures.

PMID- 15453487
TI  - Evaluation of a colostrum supplement, with or without trypsin inhibitor, and an
      egg protein milk replacer for dairy calves.
AB  - Forty-eight Holstein bull calves were assigned to a 2 x 2 x 2 factorial
      arrangement in a completely randomized block design. Main effects were colostrum
      versus a serum-derived colostrum supplement, 0 versus 1 g of trypsin inhibitor
      added at the initial 2 feedings, and milk replacer containing 0 or 50% CP from
      whole egg. Calves were bled at 0, 6, 12, 18, and 24 h after birth for
      determination of serum immunoglobulin (Ig). G. Serum IgG concentrations were
      lower in calves consuming the colostrum supplement compared with calves consuming
      colostrum. Apparent efficiency of absorption of IgG was similar. Trypsin
      inhibitor did not affect IgG concentrations or absorption of IgG. Calves were fed
      either milk replacer for 28 to 35 d (preweaning phase) and weaned when they
      consumed 0.7 kg of starter grain for 2 consecutive days. The postweaning phase
      was from weaning to d 56. Feeding colostrum supplement resulted in higher fecal
      scores postweaning (1.90 vs. 1.58) and overall (1.85 vs. 1.65) and fewer days
      medicated preweaning (5.1 vs. 2.2 d) and postweaning (3.9 vs. 1.9 d) and overall
      (9.0 vs. 4.2 d). Calves were treated for upper respiratory tract infections and
      diarrhea. Dry matter intake and weaning age were not affected by treatment.
      Postweaning (1.69 vs. 1.2 kg) and overall (1.22 vs. 1.0 kg), calves that received
      colostrum and egg milk replacer consumed more dry matter and starter.
      Postweaning, calves fed colostrum and egg milk replacer had similar or greater
      body weight and gains compared with calves fed colostrum and milk protein milk
      replacer. Preweaning, feed efficiency was greater for calves fed colostrum (0.44
      vs. 0.34), trypsin inhibitor (0.42 vs. 0.36), and milk protein milk replacer
      (0.48 vs. 0.30) compared with calves fed colostrum supplement, no trypsin
      inhibitor, and egg milk replacer, respectively. Trypsin inhibitor increased feed
      efficiency postweaning. Calves fed trypsin inhibitor and milk protein milk
      replacer were more efficient preweaning and overall than calves fed trypsin
      inhibitor and egg milk replacer. Results indicate that the blood derived
      colostrum supplement did not provide as much IgG as colostrum (4.55 g/L vs. 14.6
      g/L, respectively), that feeding 1.0 g of trypsin inhibitor did not enhance serum
      IgG concentrations, and that the egg milk replacer-fed calves fed colostrum
      performed nearly as well as calves fed colostrum and the milk protein milk
      replacer.

PMID- 15453488
TI  - Comparison of analytical methods and the influence of milk components on milk
      urea nitrogen recovery.
AB  - The objectives of this study were to compare analytical instruments used in
      independent laboratories to measure milk urea nitrogen (MUN) and determine
      whether any components in milk affect the recovery of MUN. Milk samples were
      collected from 100 Holstein cows fed one ration in a commercial dairy herd with a
      rolling herd average of 9500 kg. Half of each sample was spiked with 4 mg/dL of
      urea N, while the other half was not, to determine recovery. Both milk samples
      (spiked and not spiked) were sent to 14 independent laboratories involved in the
      MUN Quality Control Program through National Dairy Herd Improvement Association
      and analyzed for MUN, fat, protein, lactose, somatic cell count (SCC), and total
      solids. The laboratories analyzed MUN using CL-10 (n = 3), Skalar (n = 2),
      Bentley (n = 3), Foss 4000 (n = 3) or Foss 6000 (n = 3) systems. When recovery of
      MUN was evaluated among the 5 analytical methods, the mean recoveries for the
      Bentley, Foss 6000, and Skalar systems were 92.1 (SE = 2.76%), 95.4 (SE = 10.1%),
      and 95.1% (SE = 7.61%), respectively, and did not differ from each other.
      However, MUN recovery was 85.0% (SE = 2.8%) for the CL-10 system and 47.1% (SE =
      9.9%) for the Foss 4000 system, both of which differed from the other 3 systems.
      Recoveries from Foss 4000, Foss 6000, and Skalar varied among laboratories using
      the same instrument. As initial MUN concentration increased, recovery decreased
      using the Bentley and CL-10 systems. Increasing milk fat resulted in a decrease
      in recovery using the Foss 6000 system. For 4 of the 5 methods, recovery of MUN
      was not associated with specific milk components. Recovery of MUN was
      inconsistent for laboratories using the Foss 4000 and the Foss 6000 method and
      using these systems may result in an overestimation or underestimation of MUN.

PMID- 15453489
TI  - Altering dietary cation-anion difference in lactating dairy cows to reduce
      phosphorus excretion to the environment.
AB  - Four early-lactating dairy cows were randomly allocated to 4 diets with dietary
      cation-anion difference [DCAD; (Na + K) - (Cl- + S2-) mEq/100 g dry matter)]
      values of +14, +18, +24, and +45. Diets were formulated to be isoenergetic and
      isonitrogenous, and supplied similar levels of P (0.46%) and Ca (0.77%). The
      salts, MgCl2, MgSO4, K2CO3, and NaHCO3 were used to alter DCAD. The main
      objective of the study was to ascertain whether a decrease in DCAD would reduce
      fecal P excretion in lactating dairy cattle. The experiment was conducted as a 4
      x 4 Latin square design with 21-d periods. During the last 5 d, diets were
      offered at a restricted level and samples of blood, milk, feces, and urine were
      collected. Measures of acid-base status of the cows were linearly related to
      DCAD, but the animals did not experience metabolic acid stress. Neither fecal P
      nor urinary P was affected by DCAD, and there was no change in overall P balance.
      Plasma P tended to increase and blood concentrations of ionized Ca were enhanced
      as DCAD decreased; P excretion in milk showed a quadratic response to DCAD. Milk
      yield and milk composition were unaffected by changes in DCAD. Although DCAD may
      have influenced P homeostasis in lactating cows, there was no evidence that,
      within the range of + 14 to + 45 mEq/ 100 g dry matter, DCAD could be used as a
      nutritional strategy to reduce manure P from dairy cattle.

PMID- 15453490
TI  - Conjugated linoleic acid increases in milk when cows fed fish meal and extruded
      soybeans for an extended period of time.
AB  - The objective of this study was to determine the effect of feeding a conjugated
      linoleic acid (CLA) stimulating diet for an extended period of time on milk cis
      9, trans-11 CLA and vaccenic acid (VA) concentrations. Twenty cows (16 Holstein
      and 4 Brown Swiss) were divided into 2 groups (n = 10 per treatment) for a 10-wk
      study. Cows in group 1 were fed a traditional corn-soybean-basal diet (control),
      while those in group 2 were fed a blend of 0.5% fish oil from fish meal and 2%
      soybean oil from extruded soybeans (FMESB) to achieve higher milk fat cis-9,
      trans-11 CLA and VA. Diets were formulated to contain 18% CP and were composed
      (dry matter basis) of 50% concentrate mix, 25% corn silage, and 25% alfalfa hay.
      Dry matter intake was not affected by diet. Milk production increased in cows fed
      the FMESB diet. Milk fat and milk protein percentages decreased with the FMESB
      diet; however, milk fat and protein yields were not affected by treatments. Milk
      fat cis-9, trans-11 CLA and VA concentration (g/100 of fatty acids) and yield
      (g/d) were 2.5-fold greater for cows fed the FMESB diet over the 10 wk of fat
      supplementation. For cows fed the FMESB diet, contents of milk fat cis-9, trans
      11 CLA and VA gradually increased from the first week of fat supplementation,
      reached the highest concentrations in wk 3, then gradually decreased during wk 4
      and 5 and then remained relatively constant until wk 10. The concentration of cis
      9, trans-11 CLA and VA from the control diet was relatively constant over the 10
      wk of fat supplementation. Concentrations of cis-9, trans-11 CLA and VA in milk
      fat can be increased within a week by feeding a blend of fish meal and extruded
      soybeans, and that increase remains relatively constant after wk 5 of fat
      supplementation.

PMID- 15453491
TI  - Glucose metabolism in lactating cows in response to isoenergetic infusions of
      propionic acid or duodenal glucose.
AB  - A bibliographical study showed that increasing supplies of glucogenic nutrients
      lead to a curvilinear increase in milk and protein yield. Increased post-hepatic
      glucose availability may be involved in the increase in milk yield. In the
      present experiment, 5 dairy cows were arranged in a 5 x 5 Latin square design to
      compare the respective effects of 2 amounts of either duodenal glucose or ruminal
      propionic acid (C3) on glucose metabolism. Treatment consisted of a grass silage
      based diet supplemented with glucogenic nutrients infused into the rumen as a
      mixture of volatile fatty acids (control) or C3 (6.5 and 13 mol/d) or as glucose
      (3.4 and 6.9 mol/d) infused into the duodenum. Treatments were isoenergetic and
      isonitrogenous and contained 100 and 115% of energy and protein requirements,
      respectively, according to the Institut National de la Recherche Agronomique.
      Glucose appearance rate (Ra) tended to increase with the level of infusions of
      both glucogenic materials and with the high dose of duodenal glucose. Plasma
      insulin-like growth factor-I (IGF-I) concentration increased with the infusion of
      glucogenic materials compared with the control and was significantly higher with
      glucose than with C3 treatments. This experiment did not indicate whether the
      increased Ra was the key mechanism to increased milk yield because milk yield
      only tended to increase and the standard error for Ra was high. With the high
      dose of glucose infused into the duodenum, the Ra increase was greater than the
      increased lactose production in milk. Because of that connection, IGF-I may also
      be involved by favoring the glucose utilization by the mammary gland.

PMID- 15453492
TI  - Effects of feeding rations with genetically modified whole cottonseed to
      lactating Holstein cows.
AB  - Two experiments were conducted to evaluate dry matter intake (DMI), milk yield,
      and milk composition from feeding rations that contained different sources of
      genetically modified whole cottonseed to Argentinean Holstein dairy cows. Twenty
      four lactating multiparous Argentinean Holstein dairy cows were used in 2
      experiments with a replicated 4 x 4 Latin square design, with cows averaging 565
      kg body weight and 53 d in milk at the beginning of the experiments. Treatments
      in Experiment 1 were: Bollgard cotton containing the cry1Ac gene, Bollgard II
      cotton containing cry1Ac and cry2Ab genes, Roundup Ready cotton containing the
      cp4 epsps gene, and a control nongenetically modified but genetically similar
      cottonseed. In Experiment 2, two commercial sources, a parental control line, and
      the transgenic cotton containing both cry1Ac and cp4 epsps genes were used as
      treatments. All cows received the same total mixed ration but with different
      whole cottonseed sources. Cottonseed was included to provide 2.50 kg per cow
      daily (dry matter [DM] basis) or about 10% of the total diet DM. The ingredient
      composition of the total mixed ration was 32% alfalfa hay, 28% corn silage, 22%
      corn grain, 17% soybean meal, and 2% minerals and vitamins. In addition, genomic
      DNA was extracted from a subset of milk samples and analyzed by polymerase chain
      reaction followed by Southern blot hybridization for small fragments of the
      cry1Ac transgene and an endogenous cotton gene, acp1. No sample was positive for
      transgenic or plant DNA fragments at the limits of detection for the assays
      following detailed data evaluation criteria. The DMI, milk yield, milk
      composition, body weight, and body condition score did not differ among
      treatments. Cottonseed from genetically modified varieties used in these studies
      yielded similar performance in lactating dairy cows when compared to non
      transgenic control and reference cottonseed.

PMID- 15453493
TI  - Preterm as compared with full-term neonatal calves are characterized by
      morphological and functional immaturity of the small intestine.
AB  - Intestinal diseases in neonatal calves may be due to morphological and functional
      immaturity. We have studied histomorphology, crypt cell proliferation rates
      (based on incorporation of 5-bromo-2'-deoxyuridine into DNA), presence of
      apoptotic cells (based on terminal deoxynucleotidyl transferase-mediated X-dUTP
      nick end labeling), and brush border enzyme activities in preterm calves (277 d
      of gestation), euthanized on d 1 (P0) or 8 (P8), and in full-term calves (290 d
      of gestation), euthanized on d 1 (F0) or 8 (F8). Vacuolated epithelial cells were
      present in ileum of P0 and F0 but not in P8 and F8. During the first 8 d, villus
      sizes, crypt depths, and proliferation rates of crypt cells in the small
      intestine of preterm calves did not significantly change. In contrast, in full
      term calves during the first 8 d, villus sizes in jejunum decreased, crypt depths
      increased in small intestine and colon, and crypt cell proliferation increased in
      duodenum and jejunum. Submucosal thickness in jejunum was highest in P0, but in
      ileum it increased with gestational age and feeding. Gestational age x feeding
      interactions indicated increased activities of aminopeptidase N and reduced
      lactase activities only in F8 and reduced dipeptidylpeptidase IV activities only
      in P8. In conclusion, in preterm calves the small intestinal epithelium was
      immature and brush border enzyme activities differed in part from those in full
      term calves.

PMID- 15453494
TI  - Dietary supplements for lactating goats by polyunsaturated fatty acid-rich
      protected fat. Effects after supplement withdrawal.
AB  - The objective of this study was to investigate the persistence of the effects of
      supplements after they were withdrawn. Two groups of 12 goats were maintained
      under semiextensive breeding conditions; they were fed indoors with a concentrate
      with alfalfa hay and olivetree leaves. Goats were in their sixth month of
      lactation at initiation of the study. During the first month of the trials, the
      concentrate supplied to the goats was either nonsupplemented (group 1) or
      supplemented with 9% polyunsaturated fatty acids (PUFA)-rich protected fat (group
      2). After this period, the 2 groups were given the nonsupplemented until the
      average daily production of milk per animal within each group had decreased to
      300 g or less. The fat supplementation supplied increased milk production and
      also improved fat and protein yield. These effects persisted after the supplement
      was withdrawn. The supplement, moreover, produced noticeable changes in the fatty
      acids profile of the milk fat, namely a reduction in the concentration of
      saturated fatty acids and an increase in that of PUFA. In contrast to the effects
      on milk production and on the yield of its main constituents, the effects on fat
      composition disappeared when the supplement was withdrawn.

PMID- 15453495
TI  - Urea synthesis by ruminal epithelial and duodenal mucosal cells from growing
      sheep.
AB  - The objective was to determine whether ruminant gut tissues have the capability
      to synthesize urea in a short-term incubation. Mixed primary cell cultures
      containing ruminal epithelial (REC) or duodenal mucosal cells (DMC) were isolated
      from growing sheep (n = 4) fed a mixed forage-concentrate diet. Cells were
      incubated (90 min) in a Krebs salts-based buffer with either acetate (5 mM) or
      propionate (5 mM) plus a combination of substrate intermediates (5 mM) for urea
      synthesis: arginine, aspartate + citrulline (AspC), aspartate + ornithine +
      ammonia (AspON), or AspON + N-carbamoylglutamate (AspONG) in a 2 x 4 factorial
      arrangement of treatments. Volatile fatty acid, propionate vs. acetate, did not
      influence net urea synthesis. For REC, net urea synthesis (nmoles x (10(6)
      cells)(-1) x 90 min(-1)) was greatest with Arg (54.5 +/- 6.3) followed by AspC
      (4.6 +/- 1.1) and AspONG (3.6 +/- 1.4). For DMC, net urea synthesis for Arg (2.1
      +/- 0.7) and AspONG (1.9 +/- 0.7) treatments was greater than for AspC (0.3 +/-
      0.7) and AspON (-0.6 +/- 0.7) treatments. Thus, for both REC and DMC, arginase
      activity appeared to be sufficient for catabolism of arginine to urea.
      Furthermore, greater urea synthesis from ammonia, ornithine and aspartate in the
      presence of the N-acetylglutamate analogue suggests that carbamoyl phosphate
      synthetase is probably rate-limiting for urea synthesis and ammonia
      detoxification by ruminant gut tissues.

PMID- 15453496
TI  - Influence of pooled colostrum or colostrum replacement on IgG and evaluation of
      animal plasma in milk replacer.
AB  - Newborn Holstein (n = 48) and Jersey (n = 30) calves were studied to compare
      absorption of immunoglobulin G (IgG) from maternal colostrum (n = 39) or
      colostrum replacement containing an Ig concentrate derived from bovine serum (n =
      39). Calves were also fed milk replacer with (n = 38) or without (n = 40) animal
      plasma (20% of crude protein) to 29 d of age to determine effect of plasma
      protein on IgG status, health, and growth. Calves were fed maternal colostrum or
      colostrum replacement at 1.5 and 13.5 h of age and provided a total of 250 or 249
      and 180 or 186 g of IgG for Holsteins and Jerseys fed maternal colostrum or
      colostrum replacement, respectively. Milk replacer (12.5% DM) was fed at 31% of
      metabolic birth weight (2 feedings/d). Plasma was sampled at 0 h, 24 h, and
      weekly to determine IgG by turbidimetric immunoassay. At blood collection, calves
      were weighed and measured to determine growth. Health scores, fecal scores, and
      grain intake were measured daily. Plasma IgG at 24 h did not differ between
      calves fed maternal colostrum (13.78 +/- 0.39 g/ L) and colostrum replacement
      (13.96 +/- 0.38 g/L). Average daily gain, withers height, hip height, body
      length, heart girth, health, and incidence of diarrhea were not different between
      treatment groups. Calves fed maternal colostrum used feed more efficiently than
      calves fed colostrum replacement. Plasma IgG and performance were not affected by
      the addition of animal plasma to milk replacer. The colostrum replacement used in
      this study provided adequate IgG for newborn calves. Animal plasma was an
      acceptable source of protein but did not enhance growth or immunity under the
      conditions of this study.

PMID- 15453497
TI  - The energy content of wet corn distillers grains for lactating dairy cows.
AB  - Forty-five energy balances were completed with 12 multiparous, lactating Holstein
      cows in a study designed to determine the energy content of wet corn distillers
      grains. Treatments were applied in a repeated switchback design and consisted of
      total mixed diets containing 31.4% corn silage, 18.4% alfalfa hay, and either
      30.7% rolled corn and 16.7% soybean meal or 17.0% rolled corn and 31.2% wet corn
      distillers grains (dry matter basis). Replacement of corn and soybean meal with
      wet corn distillers grains reduced dry matter intake 10.9% but did not affect
      milk production. Neither digestible nor metabolizable energy were affected by
      diet composition. Heat and milk energy output did not differ by diet, but body
      energy retained was 2.8 Mcal/d less in cows fed the wet corn distillers grains
      diet. Multiple regression estimates of maintenance metabolizable energy
      requirement and partial efficiencies of metabolizable energy used for lactation
      and body energy deposition did not differ by diet. Pooled estimates were 136.2,
      0.66, and 0.85, kcal of metabolizable energy/ body weight0.75 per day,
      respectively. Calculated by difference, wet corn distillers grains was estimated
      to contain 4.09, 3.36, and 2.27 Mcal/kg of dry matter as digestible,
      metabolizable, and lactational net energy, respectively. These energy estimates
      were 7 to 11% and 10 to 15%, respectively, greater than those reported for dried
      corn distillers grains by the 1989 and 2001 dairy NRC publications.

PMID- 15453498
TI  - Effect of sodium laurate on ruminal fermentation and utilization of ruminal
      ammonia nitrogen for milk protein synthesis in dairy cows.
AB  - A crossover design trial with 4 ruminally and duodenally cannulated lactating
      dairy cows was conducted to study the effect of sodium laurate on ruminal
      fermentation, nutrient digestibility, and milk yield and composition. The daily
      dose of sodium laurate (0, control or 240 g/cow, LA) was divided in 2 equal
      portions and introduced directly into the rumen through the cannula before
      feedings. Ruminal samples (29 in 114 h) were analyzed for fermentation variables
      and protozoal counts. Sodium laurate had no effect on ruminal pH and total and
      individual volatile fatty acids concentrations. Ruminal ammonia concentration,
      ammonia N pool size, and the irreversible loss of ammonia N were unaffected by
      treatment. Compared to control, protozoal counts were reduced by 91% by LA.
      Carboxymethylcellulase and xylanase activities of ruminal fluid were decreased
      (by 40 and 36%, respectively), and amylase activity was not affected by LA
      compared with control. Flow of microbial N to the duodenum was reduced by LA. Dry
      matter intake and apparent total tract digestibility of dry matter, organic
      matter, crude protein, neutral detergent fiber, and acid detergent fiber were not
      different between the 2 treatments. Milk yield, fat-corrected milk yield, milk
      fat and protein concentrations and yields, and milk urea N content were not
      affected by treatment. Sodium laurate did not affect transfer of ruminal ammonia
      15N into bacterial or milk protein. In conclusion, LA at approximately 0.3% of
      the rumen weight reduced ruminal protozoal population and had a negative effect
      on fibrolytic activities of ruminal fluid and microbial protein flow to the
      intestine. Treatment had no other significant effects on ruminal fermentation,
      total tract digestibility, or transfer of ruminal ammonia-15N into milk protein.

PMID- 15453499
TI  - Effects of supplemental yeast (Saccharomyces cerevisiae) culture on rumen
      development, growth characteristics, and blood parameters in neonatal dairy
      calves.
AB  - Yeast (Saccharomyces cerevisiae) culture was added to a texturized calf starter
      at 0 (control), 1, or 2% of dry matter to determine effects on intake, growth,
      blood parameters, and rumen development. Seventy-five Holstein calves (38 male;
      37 female) were started on the experiment at 2 +/- 1 d of age and were studied
      for 42 d. Starter intake was measured, and fecal scoring was conducted daily.
      Growth and blood parameter measurements were recorded at weekly intervals. A
      subset of 6 male calves (2 per treatment) was euthanized at 5 wk of age, and
      rumen tissue was sampled for rumen epithelial growth measurements. An additional
      6 male calves were euthanized at 6 wk of age for rumen epithelial growth
      measurements. Inclusion of yeast culture at 2% of the starter ration
      significantly increased starter and total dry matter intake, average daily gain,
      and daily hip width change when compared with the control treatment. Average
      daily gain was improved by 15.6% for the 2% yeast treatment. Daily change in hip
      height was also significantly greater for calves receiving 2% supplemental yeast
      culture than for calves receiving 1%. No significant treatment differences were
      observed for any other variables. These data suggest that the addition of yeast
      culture in a dairy calf starter at 2% enhances dry matter intake and growth and
      slightly improves rumen development in dairy calves.

PMID- 15453500
TI  - Effects of monensin on ruminal forage degradability and total tract diet
      digestibility in lactating dairy cows during grain-induced subacute ruminal
      acidosis.
AB  - The effects of monensin premix supplementation on ruminal pH characteristics and
      forage degradability, and total tract diet digestibility during grain-induced
      subacute ruminal acidosis (SARA) in lactating dairy cows receiving a total mixed
      ration were investigated. Six multiparous, rumen-fistulated Holstein cows were
      used in a 2-treatment, 2-period (5 wk per period) crossover design. During wk 5
      (d 29 to 35) of each period, SARA was induced using a grain challenge model, and
      ruminal pH was measured continuously using indwelling pH probes. Ruminal
      degradation of corn silage and alfalfa haylage was determined using the in situ
      (nylon bag) technique, and total tract diet digestibility was determined by total
      fecal collection during wk 5. Monensin supplementation did not affect dry matter
      intake, milk yield, and composition, and ruminal pH characteristics under these
      experimentally induced SARA conditions. Rates of ruminal forage fiber
      degradability were similar between control and monensin-treated cows; however,
      monensin supplementation increased total tract fiber digestion. This study
      indicates that monensin altered total tract nutrient digestion by increasing
      fiber digestion at postruminal sites.

PMID- 15453501
TI  - A comparison of instruments and laboratories used to measure milk urea nitrogen
      in bulk-tank milk samples.
AB  - The objective of this study was to compare the instruments and laboratories that
      are currently used for analysis of milk urea nitrogen (MUN) for bulk-tank milk
      samples. Two replicate samples from each bulk tank on 10 different dairy farms
      were sent to 12 Dairy Herd Improvement Association (DHIA) laboratories throughout
      the US for MUN analysis. Two laboratories used 2 different methods for MUN
      analysis for a total of 14 analyses on 20 samples (n = 280). Values of MUN were
      analyzed using a random effects model with farm, laboratory, and farm x
      laboratory variance components. Greater than 98% of the variance in measured MUN
      was attributed to farm-to-farm variance for analysis of MUN by the Bentley, CL
      10, Foss 6000, and Skalar instruments. However, for the laboratories using the
      Foss 4000 system, <60% of the variance in MUN was attributed to farm-to-farm
      variance. Laboratories using the Bentley, CL 10, Foss 6000, and Skalar
      instruments provided slightly different results for MUN analysis, but >95% of
      sample measurements fell within 1.75 mg/ dL of each other. The laboratories using
      Foss 4000 differed from each other, and 95% of samples fell within 5 mg/dL of the
      CL 10 measurement. Laboratories using the Foss 4000 instrument did not
      consistently provide measurements of MUN that were similar to each other or to
      the measurements of the other instruments.

PMID- 15453502
TI  - Effects of feeding micronized and extruded flaxseed on ruminal fermentation and
      nutrient utilization by dairy cows.
AB  - Four lactating Holstein cows with ruminal and duo-denal cannulas were used in a 4
      x 4 latin square design to determine the effects of feeding heat-treated flaxseed
      on ruminal fermentation and site and extent of nutrient utilization. Four diets
      were formulated: a control diet with no flaxseed, a raw flaxseed diet (RF), a
      micronized flaxseed diet (MF), and an extruded flaxseed diet (EF). Flaxseed diets
      contained 12.6% flaxseed (dry matter [DM] basis). Ruminal pH, NH3 N, and total
      concentration of volatile fatty acids were not affected by dietary treatments.
      However, feeding flaxseed decreased the molar proportion of acetate and increased
      that of propionate. Flaxseed supplementation had no effect on ruminal digestion
      of DM, organic matter (OM), neutral detergent fiber (NDF), crude protein (CP),
      fatty acids (FA), and gross energy. However, ruminal digestion of acid detergent
      fiber (ADF) was lower for cows fed the flaxseed diets than for cows fed the
      control diet. Feeding flaxseed tended to increase post-ruminal and total tract
      digestibilities of DM, OM, NDF, and gross energy. Feeding heat-treated flaxseed
      diets relative to RF had no effect on ruminal, post-ruminal, and total tract
      nutrient digestibilities. Cows fed EF had higher ruminal and lower post-ruminal
      digestibilities of DM, OM, ADF, CP, and FA than cows fed MF. However, total tract
      digestibilities were similar for the 2 heat treatments. It was concluded that
      flaxseed supplementation improved total tract nutrient utilization with no
      adverse effects on ruminal fermentation. Extrusion failed to protect flaxseed
      from ruminal digestion. However, micronization can be used to increase the
      ruminal undegraded protein value of flaxseed.

PMID- 15453503
TI  - Diurnal variation in ruminal pH on the digestibility of highly digestible
      perennial ryegrass during continuous culture fermentation.
AB  - Dairy cows grazing high-digestibility pastures exhibit pronounced diurnal
      variation in ruminal pH, with pH being below values considered optimal for
      digestion. Using a dual-flow continuous culture system, the hypothesis that
      minimizing diurnal variation in pH would improve digestion of pasture when pH was
      low, but not at a higher pH, was tested. Four treatments were imposed, with pH
      either allowed to exhibit normal diurnal variation around an average pH of 6.1 or
      5.6, or maintained at constant pH. Digesta samples were collected during the last
      3 d of each of four, 9-d experimental periods. A constant pH at 5.6 compared with
      a constant pH of 6.1 reduced the digestibility of organic matter (OM), neutral
      detergent (NDF), and acid detergent fiber (ADF) by 7, 14, and 21%, respectively.
      When pH was allowed to vary (averaging 5.6), digestion of OM, NDF, and ADF were
      reduced by 15,30, and 36%, respectively, compared with pH varying at 6.1. There
      was little difference in digestion parameters when pH was either constant or
      varied with an average pH of 6.1. However, when average pH was 5.6, maintaining a
      constant pH significantly increased digestion of OM, NDF, and ADF by 5, 25, and
      24% compared with a pH that exhibited normal diurnal variation. These in vitro
      results show that gains in digestibility and potential milk production can be
      made by minimizing diurnal variation in ruminal pH, but only when ruminal pH is
      low (5.6). However, larger gains in productivity can be achieved by increasing
      average daily ruminal pH from 5.6 to 6.1.

PMID- 15453504
TI  - Effect of liquid flavor supplementation of the diet on dairy cows in the
      transition period.
AB  - A 9-wk trial was conducted to study the performance of 24 Holstein cows during
      the transition period (3 wk prepartum to 6 wk postpartum). Cows were assigned to
      either a control or liquid-flavored (0.52 mL/kg of feed) total mixed ration in a
      randomized complete block design. The diets contained corn silage, alfalfa
      haylage, cottonseed, and a grain mix based on ground corn and soybean meal. Cows
      were fed to ensure 10% orts, and the diet provided (on a dry matter basis) 13%
      crude protein, 32% acid detergent fiber, 44% neutral detergent fiber, and 1.54
      Mcal/kg of NEL prepartum and 17.5% crude protein, 30% acid detergent fiber, 40%
      neutral detergent fiber, and 1.57 Mcal/kg of NEL postpartum. An additional 2.3 kg
      of alfalfa hay was fed during the first 5 d postpartum. Weekly means of dry
      matter intake (DMI), milk yield, milk protein, milk fat, SNF, somatic cell
      counts, and body weight (BW) were analyzed using a repeated measures procedure.
      There was no effect of treatment on these variables, and least squares means were
      16.9 and 15.7 kg/d for DMI, 38 and 35.3 kg/d for milk yield, 3.10 and 3.11% for
      milk protein, 3.69 and 3.74% for milk fat, 8.37 and 8.16% for SNF, 1.99 x 10(5)
      and 4.33 x 10(5) for somatic cell count, and 631 and 651 kg for BW for cows fed
      control and flavored diets, respectively. Individual cow daily DMI data were
      fitted to an exponential model describing pre- and postpartum feed consumption
      [DMI = a - b x e(-c x t), where DMI was measured in kg, a = asymptotic DMI, b =
      potential fractional increase in DMI, c = fractional rate of increase in DMI, and
      t = days prior to calving or days in milk]. Fractional rates of increase in DMI
      were similar: 0.139 and 0.123/d for control and flavored diets, respectively.
      Data for both groups were separately analyzed using multiple regression with 3.5%
      fat-corrected milk as the dependent variable and BW and DMI as independent
      variables. More BW was mobilized per unit increase in 3.5% fat-corrected milk in
      cows fed the control than in cows fed the flavored diet. Cows fed the control
      diet tended to be in more negative energy balance during early lactation than
      cows fed the flavored diet. It was concluded that feeding flavor improved energy
      balance of cows in early lactation and may reduce the risk of health or
      reproductive problems.

PMID- 15453505
TI  - Effects of milk urea nitrogen and other factors on probability of conception of
      dairy cows.
AB  - The objective of this study was to evaluate the relationships between milk urea
      nitrogen (MUN) and other factors and the probability of conception in dairy cows.
      Data were retrieved from the Lancaster Dairy Herd Improvement Association (DHIA).
      A total of 713 dairy herds and 10,271 dairy cows were included in the study.
      Logistic regression was used to determine the within-herd effects of MUN, milk
      production, lactation number, and breeding season on the probability of
      conception for each of 3 services. Within herds, MUN displayed a slight negative
      association with probability of conception at first service. For example, there
      was a 2- to 4-percentage unit decrease in conception rate at first service with a
      10-mg/dL increase in MUN. In among-herd regression analysis, there was no effect
      of MUN on probability of conception. These results suggest that MUN may be
      related to conditions affecting reproduction of individual cows within a herd.
      Diet formulation usually would affect MUN equally among all cows at a similar
      stage of lactation in a herd. Because there was no effect of MUN among herds,
      diet formulation did not appear to affect conception rate.

PMID- 15453506
TI  - Increasing amounts of conjugated linoleic acid progressively reduces milk fat
      synthesis immediately postpartum.
AB  - Mixed conjugated linoleic acid (CLA) isomers decrease milk fat synthesis during
      established lactation, but their ability to cause milk fat depression (MFD)
      immediately postpartum remains unclear. Multiparous Holstein cows (n = 19) were
      randomly assigned to 1 of 4 doses of rumen-protected (RP) CLA supplements (0,
      200, 400, and 600 g/d); each dose provided equal amounts of fatty acids by
      replacing and balancing treatments with an RP supplement of palm fatty acid
      distallate. Doses provided a total of 468 g fatty acids/d and 0, 62, 125, or 187
      g of mixed CLA isomers/d, respectively. The CLA supplement contained a variety of
      CLA isomers: 5.4% trans-8, cis-10; 6.3% cis-9, trans-11; 7.9% trans-10, cis-12;
      and 8.2% cis-11, trans-13 CLA. Each group received treatments from approximately 
      10 to 21 d relative to calving. To improve palatability and ensure complete
      consumption, doses were mixed with equal amounts of steam-flaked corn and dried
      molasses; one-half the supplement was fed at 0600 h, and the remaining supplement
      was fed at 1800 h. Milk yield and individual feed intake were recorded daily, and
      milk samples were obtained from each cow every 2nd day (at both milkings)
      starting on d 1 postpartum. There were no differences in dry matter intake (17.1
      kg/d), milk yield (34.2 kg/d), protein content (3.74%), lactose content (4.61%),
      or yield of milk protein or lactose. The CLA supplementation decreased overall
      milk fat content in a dose-responsive manner (4.57, 3.97, 3.32, and 3.10,
      respectively), and milk fat yield displayed the same progressive decline. The
      dose-dependent decrease in milk fat content was evident during wk 1 and became
      highly significant during wk 2 and 3. The milk fat yield response pattern was
      similar, and by d 21, the highest RP-CLA supplement decreased milk fat content
      and yield by 49 and 56%, respectively. These data clearly indicate RP-CLA can
      markedly (40 to 50%) induce MFD immediately postpartum without negatively
      affecting other production parameters.

PMID- 15453507
TI  - Derivation and calculation of approximate reliabilities and daughter yield
      deviations of a random regression test-day model for genetic evaluation of dairy
      cattle.
AB  - Test-day milk, fat, protein yield, and somatic cell score (SCS) were analyzed
      separately using data from the first 3 lactations and a random regression model.
      Data used in the model were from Austria, Germany, and Luxembourg and from
      Holstein, Red, and Jersey dairy cattle. For reliability approximation, a multiple
      trait effective daughter contribution (MTEDC) method was developed under general
      multiple trait models, including random regression test-day models, by extending
      the single-trait daughter equivalents concept. The MTEDC was applied to the very
      large dairy population, with about 15.5 million animals. The calculation of
      reliabilities required less computer memory than the corresponding iteration
      program and a significantly lower computing time equivalent to 24 rounds of
      iteration. A formula for daughter-yield deviations was derived for bulls under
      multiple-trait models. Reliability associated with daughter-yield deviations was
      approximated using the MTEDC method. Both the daughter-yield deviation formula
      and associated reliability method were verified in a simulation study using the
      random regression test-day model. Correlations of lactation daughter-yield
      deviations with estimated breeding values calculated from a routine genetic
      evaluation were 0.996 for all bulls and 0.95 for young bulls having only
      daughters with short lactations.

PMID- 15453508
TI  - Estimated heterogeneity of phenotypic variance of test-day yield with a
      structural variance model.
AB  - First-lactation test-day milk, fat, and protein yields from New York, Wisconsin,
      and California herds from 1990 through 2000 were adjusted additively for age and
      lactation stage. A random regression model with third-order Legendre polynomials
      for permanent environmental and genetic effects was used. The model included a
      random effect with the same polynomial regressions for 2 yr of calvings within
      herd (herd-time effect) to provide herd-specific lactation curves that can change
      every 2 yr. (Co)variance components were estimated using expectation-maximization
      REML simultaneously with phenotypic variances that were modeled using a
      structural variance model. Maximum heritability for test-day milk yield was
      estimated to be approximately 20% around 200 to 250 d in milk; heritabilities
      were slightly lower for test-day fat and protein yields. Herd-time effects
      explained 12 to 20% of phenotypic variance and had the greatest impact at start
      of lactation. Variances of test-day yields increased with time, subclass size,
      and milking frequency. Test month had limited influence on variance. Variance
      increased for cows in herds with low and high milk yields and for early and late
      lactation stages. Repeatabilities of variances observed for a given class of
      herd, test-day, and milking frequency were 14 to 17% across nested variance
      subclasses based on lactation stage.

PMID- 15453509
TI  - Genetic parameters for test-day electrical conductivity of milk for first
      lactation cows from random regression models.
AB  - Electrical conductivity (EC) of milk has been introduced as an indicator trait
      for mastitis during the last few decades. The correlation of EC to mastitis, easy
      access to EC data, and the low cost of recording are properties that make EC a
      good indicator trait for mastitis. In this study, EC was measured daily during
      the lactation and available from 2101 first-lactation Holstein cows in 8 herds in
      the United States. Data were analyzed with an animal model that included herd
      test-day, age at calving and days in milk (DIM) as fixed effects, and random
      additive genetic and permanent environmental effects. A repeatability model and 5
      random regression (RR) models with increasing order of Legendre polynomials were
      used. The goodness of fit for the different models was evaluated based on several
      tests. Our results indicate that the best model was a RR model with a fourth
      order Legendre polynomial for both additive genetic and permanent environmental
      effects. Heritability estimates obtained with this model were from 0.26 to 0.36.
      Due to the relatively high heritability obtained for EC of milk, EC might be a
      potential indicator trait to use in a breeding program designed to reduce the
      incidence of mastitis.

PMID- 15453510
TI  - Prediction of daily milk, fat, and protein production by a random regression test
      day model.
AB  - Test-day genetic evaluation models have many advantages compared with those based
      on 305-d lactations; however, the possible use of test-day model (TDM) results
      for herd management purposes has not been emphasized. The aim of this paper was
      to study the ability of a TDM to predict production for the next test day and for
      the entire lactation. Predictions of future production and detection of outliers
      are important factors for herd management (e.g., detection of health and
      management problems and compliance with quota). Because it is not possible to
      predict the herd-test-day (HTD) effect per se, the fixed HTD effect was split
      into 3 new effects: a fixed herd-test month-period effect, a fixed herd-year
      effect, and a random HTD effect. These new effects allow the prediction of future
      production for improvement of herd management. Predicted test-day yields were
      compared with observed yields, and the mean prediction error computed across
      herds was found to be close to zero. Predictions of performance records at the
      herd level were even more precise. Discarding herds enrolled in milk recording
      for <1 yr and animals with very few tests in the evaluation file improved
      correlations between predicted and observed yields at the next test day
      (correlation of 0.864 for milk in first-lactation cows as compared with a
      correlation of 0.821 with no records eliminated). Correlations with the observed
      305-d production ranged from 0.575 to 1 for predictions based on 0 to 10 test-day
      records, respectively. Similar results were found for second and third lactation
      records for milk and milk components. These findings demonstrate the predictive
      ability of a TDM.

PMID- 15453511
TI  - A multiple-component analysis of US dairy trade.
AB  - This paper develops a multiple component-based methodology to account for imports
      and exports of dairy products and products with a significant dairy content. More
      specifically, it accounts for imports, exports, and net trade for all dairy
      products on the basis of milk fat, protein, other solids, and moisture. This
      approach provides a less biased method of assessing the amount of dairy imports
      entering the US than the USDA's milk equivalent conversions.

PMID- 15453512
TI  - Description and validation of the Moorepark Dairy System Model.
AB  - A stochastic budgetary simulation model of a dairy farm was developed to allow
      investigation of the effects of varying biological, technical, and physical
      processes on farm profitability. The model integrates animal inventory and
      valuation, milk supply, feed requirement, land and labor utilization, and
      economic analysis. A key model output is the estimated distribution of farm
      profitability, which is a function of total receipts from milk, calves, and cull
      cows less all variable and fixed costs (including an imputed cost for labor). An
      application of the model was demonstrated by modeling 2 calving patterns: a mean
      calving date of February 24 (S1) and a mean calving date of January 27 (S2).
      Monte Carlo simulation was used to determine the influence of variation in milk
      price, concentrate cost, and silage quality on farm profitability under each
      scenario. Model validation was conducted by comparing the results from the model
      against data collected from 21 commercial dairy farms. The net farm profit with
      S1 was 53,547 euros, and that with S2 was 51,687 euros; the annual EU milk quota
      was 468,000 kg, and farm size was 40 ha. Monte Carlo simulation showed that the
      S1 scenario was stochastically dominant over the S2 scenario. Sensitivity
      analyses showed that farm profit was most sensitive to changes in milk price. The
      partial coefficients of determination were 99.2, 0.7, and 0.1% for milk price,
      concentrate cost, and silage quality, respectively, in S1; the corresponding
      values in S2 were 97.6, 2.3, and 0.1%. Validations of the model showed that it
      could be used with confidence to study systems of milk production under Irish
      conditions.

PMID- 15453513
TI  - Somatoform disorders after temporal lobectomy.
AB  - OBJECTIVE: Depression, anxiety, and psychosis are the most frequent psychiatric
      disorders after epilepsy surgery. The only new-onset somatoform disorder reported
      postoperatively is conversion disorder. We identified 10 patients who developed
      somatoform disorder other than nonconversion epileptic seizures after anterior
      temporal lobectomy. METHOD: We retrospectively reviewed the charts of 325
      anterior temporal lobectomy and 125 extratemporal surgeries between 1991 and
      2000. RESULTS: Seven of the patients developed undifferentiated somatoform
      disorder after anterior temporal lobectomy, 1 had pain and body dysmorphia,
      another had pain disorder, and another had body dysmorphia alone, but none were
      found after extratemporal surgeries (chi-square = 3.93; P < or = 0.05).
      Somatoform disorder was significantly more common in right anterior temporal
      lobectomy (n = 9) than left anterior temporal lobectomy (n = 1) (chi-square =
      6.5; P < or = 0.025). CONCLUSIONS: Our findings suggest that right temporal
      resection contributes to the development of somatoform disorders in our patients
      and that right temporal dysfunctions may contribute to idiopathic somatoform
      disorders.

PMID- 15453514
TI  - Differential effect of right and left basal ganglionic infarctions on procedural
      learning.
AB  - OBJECTIVE: To assess the effect of ischemic infarctions affecting the basal
      ganglia (BG) region on a series of procedural learning tasks. BACKGROUND: The
      basal ganglia hypothesis of procedural learning is a matter of debate. As most of
      the relevant research so far is based on examination of patients suffering from
      Parkinson disease, this inconsistency might reflect either lesion heterogeneity
      existing in this pathologic group or the heterogeneity of the procedural learning
      tasks. METHOD: Twelve patients with lesions confined to the right (BGr), 10 to
      the left (BGI) BG region, and 15 matched controls participated in the study.
      Three procedural learning tasks were used: Tower of Hanoi Puzzle, Mirror Reading,
      and Porteus Mazes. Declarative memory and general intelligence were also tested.
      RESULTS: Verbal declarative memory was impaired in the BG1 group. For each
      procedural learning task, baseline performance and learning rate were analyzed.
      Tower of Hanoi Puzzle: Baseline performance of the BG1 group was impaired
      compared with the other groups. The BGr group was the only group that did not
      improve over learning trials. MR: Baseline performance of the BGr group was
      impaired compared with the other groups. The groups' learning rate did not differ
      significantly. Porteus Mazes: Baseline performance of both patient groups was
      impaired compared with that of the control group. Learning rate over repetitive
      trials of the same maze was impaired in the BGr group. However, the transfer of
      procedural learning to a newly exposed maze was impaired in the BG1 group.
      CONCLUSIONS: First, right and left basal ganglia play different roles in
      different procedural learning tasks. Second, procedural learning is not a unitary
      capacity subserved by any single neural mechanism.

PMID- 15453515
TI  - Clock drawing errors in dementia: neuropsychological and neuroanatomical
      considerations.
AB  - OBJECTIVES: A clock drawing test scoring system is presented to explore the
      neuropsychological/neuroanatomic components underlying clock drawing in patients
      initially diagnosed with Alzheimer disease, ischemic vascular dementia associated
      with white matter alterations, and Parkinson disease. METHODS: Fourteen clock
      drawing test errors were scored to create 4 clock drawing test subscales that
      assess different underlying cognitive operations. RESULTS: In the command
      condition, errors on the Time subscale were correlated with impairment on
      executive control measures. In the copy condition, errors on the
      Perseveration/Pull to Stimulus subscale was also correlated with executive
      control measures. Patients presenting with mild (low) magnetic resonance imaging
      white matter alterations, significant (high) white matter alterations, and
      Parkinson disease were compared. In the command condition, the low white matter
      alterations group made fewer total errors than the Parkinson disease group. In
      the copy condition, the low white matter alterations group made fewer errors on
      the Time, Spatial Layout, and Perseveration/Pull to Stimulus clock drawing test
      subscales than the high white matter alterations or Parkinson disease groups. Few
      differences were noted between the high white matter alterations and Parkinson
      disease groups. DISCUSSION: Our data suggest that heavy demands on executive
      control associated with the interruption of large-scale cortical-subcortical
      neural networks underlie impairment in clock drawing in mild dementia.

PMID- 15453516
TI  - Cerebral correlates of varying ages of emotional memories.
AB  - OBJECTIVE: The purpose of the present study was to investigate the cerebral
      correlates of varying ages of emotional memories using quantitative
      electroencephalography. BACKGROUND: Recollection of emotional memories has often
      been used as a method of inducing emotional arousal in studies seeking to
      investigate the cerebral correlates of emotional arousal. However, the specific
      effects of the ages of the memories recalled on resulting changes in cerebral
      activity have not been investigated. METHOD: A total of 16 female undergraduates
      were asked to recollect an angry memory while quantitative electroencephalography
      was recorded. Following recollection, they were further asked to indicate the age
      of the memory recalled. RESULTS: The results indicated that significant
      correlations existed between ages of angry memories and changes in the magnitude
      of low beta (13 to 21 Hz) and high beta (21 to 32 Hz) at the right frontal, left
      temporal, and bilateral parietal regions of the brain. CONCLUSIONS: The results
      support an integration of the spreading activation and parallel distributed
      processing models of memory in predicting the cerebral effects of varying ages of
      emotional memories. Further, given the present findings, it may be important for
      investigators to determine the ages of the memories recalled so as to control or
      otherwise account for the effects of this potentially confounding variable.

PMID- 15453517
TI  - Effect of anxiolytics on cognitive flexibility in problem solving.
AB  - OBJECTIVE: Our purpose is to examine the effect of different classes of
      anxiolytics on cognitive flexibility. BACKGROUND: Situational stressors and
      anxiety impede performance on "creativity" tests requiring cognitive flexibility.
      Noradrenergic agents have been shown to modulate cognitive flexibility as
      assessed by performance on anagrams. To determine whether these findings on
      noradrenergic modulation of cognitive flexibility are specific to the
      noradrenergic system or are a nonspecific anxiety effect, we compared the effects
      of propranolol, lorazepam, and placebo on the anagram task. METHODS: Subjects
      attended 3 test sessions. Prior to each session, subjects were given 1 of the 3
      drugs. As in previous research, the natural log of the solution latency of each
      test item was summed for each test session and compared across drug conditions.
      RESULTS: For subjects able to solve the anagrams, solution times after
      propranolol, but not lorazepam, were significantly lower than after placebo.
      CONCLUSIONS: Therefore, this suggests that the phenomenon of noradrenergic
      modulation of cognitive flexibility does not result from a nonspecific anxiolytic
      effect, but rather is specific to the noradrenergic system.

PMID- 15453518
TI  - Verbal memory errors and symptoms in schizophrenia.
AB  - OBJECTIVE: To extend and test hypotheses linking positive and negative symptoms
      to selective aspects of verbal memory in schizophrenia. BACKGROUND: Verbal memory
      includes the ability to discriminate and prevent the intrusion of irrelevant
      information into recall and recognition. This ability has been proposed as a
      cognitive process that differentially mediates positive and negative symptoms.
      METHOD: Four error discrimination and 1 general recall memory index from the
      California Verbal Learning Test as well as general ability (IQ) and sex were used
      as predictors of symptom ratings in 55 schizophrenia patients within a regression
      framework. RESULTS: Intrusion errors during free recall contributed significantly
      to the prediction equation for negative symptoms (Brief Psychiatric Rating
      Scale). In contrast, positive symptoms and general psychopathology were not
      predicted by any of the discrimination indices. However, general recall memory
      (California Verbal Learning Test total words trials 1-5) contributed
      significantly to the prediction of general psychopathology and marginally to the
      prediction of negative symptoms. CONCLUSIONS: Impaired recall memory predicts
      levels of nonspecific psychopathology in schizophrenia. Negative symptoms
      associate with low intrusion error rates, but there is no evidence of an
      association between elevated errors and positive symptoms.

PMID- 15453519
TI  - Primacy and recency effects found using affective word lists.
AB  - This experiment tested hypotheses linking the right cerebral regulation of
      hostility and affective verbal learning. First, patterns of recall for positive,
      negative, and neutral affective list learning among high- and low-hostile
      individuals were examined. It was expected that low-hostiles would recall more
      items from the positive list and that high-hostiles would recall more words from
      the negative affective list. Also, independent of groups, it was expected that
      there would be a primacy effect for negative words and a recency effect for
      positive words. Exploratory analyses examined the relation between hostility and
      primacy and recency effects on the positive and negative word lists. High- and
      low-hostile participants (n = 65) completed the positive list learning task, the
      negative list learning task, or the neutral list learning task. Data analyses
      revealed no significant difference between the high- and low-hostile groups on
      the different affective lists. However, results of the present investigation
      reliably demonstrated the predicted primacy and recency effects. There was a
      primacy effect for the negative affective list and a recency effect for the
      positive affective list. These findings are consistent with previous research
      investigating the acquisition pattern of affective verbal learning.

PMID- 15453520
TI  - A pilot safety study of repetitive transcranial magnetic stimulation (rTMS) in
      Tourette's syndrome.
AB  - OBJECTIVE: We designed a randomized, blinded, crossover study to assess safety
      and test whether transcranial magnetic stimulation at specific regions and
      frequencies might modify tics. We administered repetitive transcranial magnetic
      stimulation over prefrontal cortex or motor cortex, with either fast or slow
      repetitive transcranial magnetic stimulation, to 8 Tourette's syndrome patients.
      METHODS: Over 5 days, we applied repetitive transcranial magnetic stimulation at
      110% of the motor threshold over left motor cortex (twice) or left prefrontal
      cortex (twice), using either 1 Hz or 15 Hz transcranial magnetic stimulation, or
      sham transcranial magnetic stimulation (once). RESULTS: All 8 subjects completed
      the study with minimal side effects and no worsening of tics or other involuntary
      movements. Ignoring site and frequency, tic symptoms improved significantly over
      the week of the study. The study design does not allow one to address whether
      this was due to the presence or frequency of transcranial magnetic stimulation or
      to nonspecific factors involved in study participation. CONCLUSIONS: Repetitive
      transcranial magnetic stimulation at these sites, doses, and use parameters
      appears to be safe in adults with Tourette's syndrome. Further studies using
      repetitive transcranial magnetic stimulation in Tourette's syndrome are
      warranted, using balanced parallel designs.

PMID- 15453521
TI  - Obsessive-compulsive disorder secondary to bilateral frontal damage due to a
      closed head injury.
AB  - OBJECTIVE: To describe a patient who exhibited obsessive-compulsive disorder and
      frontal lobe dysfunction signs after a closed head trauma. BACKGROUND: Recent
      evidence indicates that frontal-subcortical circuits are involved in the
      pathogenesis of primary obsessive-compulsive disorder. There are a number of case
      reports of secondary obsessive-compulsive disorder after lesions involving
      certain parts of these circuits. METHOD: Clinical examinations, cognitive and
      behavioral assessments, and-lesion analysis based on magnetic resonance imaging
      were conducted. RESULTS: The patient displayed marked obsessive-compulsive
      behavior along with hyperorality and apathy. Magnetic resonance imaging showed
      symmetrical frontal-polar abnormal signal intensity. Topographic lesion analysis
      revealed involvement of Brodmann areas 11, 10, 24, 25, and 32. CONCLUSIONS: The
      patient presented in this report had both frontal lobe dysfunction signs and
      obsessive-compulsive disorder secondary to bilateral frontal damage due to a
      closed head injury. The etiological significance of head injury and frontal lobe
      involvement in obsessive-compulsive disorder is discussed in the context of the
      clinical and neuroimaging findings and of previous series of brain injured
      patients.

PMID- 15453522
TI  - Intracranial spread of Merkel cell carcinoma through intact skull.
AB  - We report an unusual case of Merkel cell carcinoma presenting as a frontal scalp
      mass with apparent invasion into underlying brain parenchyma through grossly
      intact calvaria. Despite wide local excision, craniectomy, intracranial tumor
      resection, and postoperative adjuvant irradiation, widespread systemic metastases
      resistant to chemotherapy developed, and the patient died 9 months after surgery.
      This case report confirms that Merkel cell carcinoma of the head and neck,
      already known to be an aggressive tumor, has the capacity for rapid intracranial
      extension. We propose that in this case, the mechanism of intracranial metastasis
      was via communicating veins rather than through bone destruction or systemic
      metastasis. Appropriate preoperative imaging should be carried out to define the
      extent of this tumor when it is adjacent to the skull. We found contrast-enhanced
      magnetic resonance imaging to be superior to computed tomography for defining
      soft tissue extent and marrow space involvement within underlying bone.

PMID- 15453523
TI  - Midline maxillary odontogenic keratocyst.
AB  - Odontogenic keratocysts are odontogenic cysts of the jaw, usually the mandible.
      We present a recurrent case in the maxilla. Immunohistochemical staining is
      necessary to distinguish the entity from other cystic lesions of the jaw, and
      aggressive surgical management is required.

PMID- 15453524
TI  - Bronchogenic cysts of the neck in adults.
AB  - Bronchogenic cysts are congenital sacs that result from maldevelopment of the
      primitive foregut. Although they occur predominantly in the chest, there are
      reports of lesions in extrathoracic locations. The majority of reported
      bronchogenic cysts located in the neck are found in the pediatric population; a
      review of the literature reveals few reports of bronchogenic cysts of the neck
      among adults. The diagnosis of a bronchogenic cyst relies on the histology and
      location of the lesion. Here, we review our experience in the diagnosis and
      management of 2 adult patients with pathologically proven bronchogenic cysts.
      Both patients presented with solitary neck masses that proved to be bronchogenic
      cysts on histologic examination. Our purpose is to define the histopathologic and
      clinical characteristics of bronchogenic cysts and discuss the features that
      distinguish them from other cervical cysts. In conclusion, congenital
      bronchogenic cysts can occur in the neck of adults and should be considered in
      the differential diagnosis of cystic cervical masses in adults, as well as
      children.

PMID- 15453525
TI  - Splaying of the carotid bifurcation caused by a cervical sympathetic chain
      schwannoma.
AB  - Splaying of the carotid bifurcation revealed by an imaging study is usually
      indicative of a carotid body tumor, but there are other possibilities. To promote
      awareness of a cervical sympathetic chain schwannoma as another cause of splaying
      of the carotid bifurcation, we present a case of cervical sympathetic chain
      schwannoma, with an additional 7 cases in the English-language literature, and
      discuss the relationship between the great vessels of the neck and a carotid body
      tumor or a schwannoma of the cervical sympathetic chain or vagus nerve from an
      anatomic viewpoint. We conclude that splaying of the carotid bifurcation with
      hypervascularity suggests a carotid body tumor, whereas in cases without
      hypervascularity, a cervical sympathetic chain schwannoma is another possibility.
      Vagus nerve schwannomas can separate the internal jugular vein and internal
      carotid artery, but seldom widen the carotid bifurcation.

PMID- 15453526
TI  - Varicella-zoster virus DNA level and facial paralysis in Ramsay Hunt syndrome.
AB  - We have investigated whether the copy number of varicella-zoster virus (VZV) in
      saliva correlates with the clinical symptoms in patients with Ramsay Hunt
      syndrome. A real-time quantitative polymerase chain reaction assay was used to
      examine the VZV DNA copy number in saliva samples from 37 patients. We detected
      VZV DNA in 6 of the 7 patients with oropharyngeal zoster lesions (86%) and in 17
      of the 30 patients who had zoster lesions only on the skin (57%). Patients with
      oropharyngeal zoster lesions had a high VZV load in their saliva, and the
      difference between the copy number in patients with oropharyngeal zoster lesions
      and those without was around 10,000 copies per 50 microL. In addition, patients
      with oropharyngeal zoster lesions showed worse recovery of facial function than
      those without. It seems that the VZV DNA level in saliva reflects the kinetics of
      viral reactivation in the facial nerve, as well as in the oropharyngeal
      epithelium, in patients with Ramsay Hunt syndrome.

PMID- 15453527
TI  - Total facial paralysis after vestibular schwannoma surgery: probability of
      regaining normal function.
AB  - The aim of the present study was to ascertain the precise fraction of vestibular
      schwannoma cases that recover to normal function after postoperative total facial
      nerve paralysis and to compare our results with those presented in the
      literature. This was a retrospective case review of 631 cases. Among the 132
      cases with immediate postoperative facial nerve palsy (House Brackmann [HB] grade
      VI), only 2 (1.5%) recovered to normal function (HB grade I). In an attempt to
      compare our results with those of other series in the literature, we found a
      large variation in the incidence of recovery of this group of patients to grade
      I, ranging from 0% to 50%. Our analysis of the reported data revealed widely
      varying methods of data collection and presentation, making a scientifically
      valid comparison particularly difficult. According to our data, complete (HB
      grade I) or near-complete (HB grade II) facial nerve function recovery from an
      immediate postoperative grade VI palsy is extremely rare.

PMID- 15453528
TI  - Biphasic ceramics and fibrin sealant for bone reconstruction in ear surgery.
AB  - Bone reconstruction is still a matter of concern in middle ear surgery despite
      the large number of surgical techniques proposed. A composite made of biphasic
      calcium phosphate ceramic granules mixed with human fibrin sealant, forming a
      moldable material that is easy to set for bone reconstruction, has been used with
      success over a 16-year period for reconstruction of the posterior canal wall or
      for mastoid obliteration. In a retrospective series of 72 ears with long-term
      follow-up (average follow-up of 46 months), regular microscopic examination, and
      computed tomographic controls, we have evaluated this bone reconstruction
      technique for radical mastoidectomy cavities or the closed technique. The bone
      reconstruction material provided an immediate anatomic reconstruction that
      remains stable and is well tolerated over the long term. A slight leakage of
      granules in the meatus was initially observed in several patients with transient
      aseptic otorrhea. Fifty-seven ears were followed up for 1 year or more.
      Satisfactory clinical results with complete regression of the mucous membrane
      disease were found in 82.4% of the patients, with perfect stability of the
      material in 65%. We did not observe any cases of recurrent cholesteatoma in or
      behind the filling material. Eighteen biopsies were performed between 8 and 84
      months after surgery during a second surgical step performed for functional
      purposes or for recurrent cholesteatoma; 17 of the 18 cases showed
      osteointegration of the filling material. After a 16-year experiment, we consider
      this technique to be a highly satisfactory procedure that could be extended to
      other situations of bone reconstruction.

PMID- 15453529
TI  - Horizontal canal benign positional vertigo.
AB  - The existence of horizontal canal benign positional vertigo (BPV) was predicted
      from temporal bone studies in 1973, but was not clinically confirmed until later.
      In this series of 300 patients with BPV, 35 (12%) were identified as having the
      horizontal canal variant. The essential features are the onset of vertigo when
      the patient assumes a supine position and bidirectional horizontal nystagmus as
      the head is turned from side to side. In one third it appeared as a canal
      "conversion" in patients undergoing repositioning treatment for posterior canal
      BPV. The mechanism can be canalithiasis or cupulolithiasis. Repositioning
      treatment is a 360 degrees horizontal head and body rotation that has a high
      success rate if the symptomatic ear is correctly identified.

PMID- 15453530
TI  - Audiovestibular evolution in a patient with multiple sclerosis.
AB  - Multiple sclerosis is characterized by the presence of multiple plaques within
      the central nervous system, manifesting as remission and exacerbation of
      neurologic dysfunction over variable time courses. We present the case of a 20
      year-old woman. Before treatment, her auditory brain stem response (ABR) test
      revealed bilateral prolongation. A caloric test showed canal paresis of the right
      ear and a normal response on the left. A vestibular evoked myogenic potential
      (VEMP) test displayed an absent response in the right ear and a delayed response
      in the left. A magnetic resonance imaging (MRI) scan demonstrated multiple
      diffuse high signal lesions in the hemispheres, brain stem, and cerebellum. Six
      months after treatment, the demyelinating plaques were shown to have resolved
      spontaneously on MRI. Recovery of caloric responses was anticipated. Bilateral
      prolongation of ABRs remained, but the VEMP test disclosed a normal response in
      the right ear and a delayed response in the left. Accordingly, in addition to
      MRI, caloric tests and ABR and VEMP tests are useful in monitoring the evolution
      of audiovestibular function in patients with multiple sclerosis.

PMID- 15453531
TI  - Pulsatile tinnitus cured by mastoidectomy.
AB  - Tinnitus of venous origin is a rare occurrence. It represents roughly half of
      cases of vascular tinnitus. The choice of treatment is not easy, even when the
      diagnosis is certain. Reassurance of the patient is often sufficient.
      Nevertheless, a surgical treatment is sometimes performed--usually ligature of
      the internal jugular vein. We present the case of a patient with a right venous
      pulsatile tinnitus and a history of 5 years of ineffective medical and surgical
      treatments. Ligature of the internal jugular vein was not chosen in this case: a
      computed tomographic scan showed filled mastoid cells, and mastoidectomy was
      performed instead. The tinnitus disappeared immediately after surgery and has not
      recurred during a 2-year follow-up. The bilateral preoperative sensorineural and
      conductive hearing loss also disappeared. Pulsatile tinnitus of venous origin is
      usually treated with ligature of the internal jugular vein. Mastoidectomy is an
      interesting alternative in selected cases.

PMID- 15453532
TI  - Effect of corticosteroid on salicylate-induced morphological changes of isolated
      cochlear outer hair cells.
AB  - Our previous studies showed that pretreatment with corticosteroids, which
      inhibits release of arachidonic acid (precursor of prostaglandins and
      leukotrienes), partially prevented salicylate-induced hearing loss in vivo. The
      purpose of this study was to determine the effect of pretreatment with
      corticosteroid (dexamethasone sodium phosphate) on isolated cochlear outer hair
      cells (OHCs) exposed to salicylate in vitro. Isolated OHCs from the chinchilla
      cochlea were exposed to salicylate with or without pretreatment with
      dexamethasone. Images were stored and analyzed on the Image program. The OHCs
      exposed to salicylate demonstrated a significant shortening in cell length. The
      OHCs exposed to salicylate after pretreatment with dexamethasone exhibited no
      significant change in cell length. We conclude that corticosteroid treatment of
      isolated OHCs is effective in blocking the morphological changes induced by
      salicylate. This study gives additional evidence that salicylate ototoxicity is
      mediated by alteration in the levels of arachidonic acid metabolites.

PMID- 15453533
TI  - Internal jugular vein tumor thrombus associated with thyroid carcinoma.
AB  - Thyroid carcinoma usually presents as an asymptomatic thyroid nodule. Thyroid
      cancer may show microscopic vascular invasion; however, internal jugular vein
      tumor thrombus is a rare complication of thyroid cancer. A unique case of
      internal jugular vein tumor thrombus associated with thyroid carcinoma is
      presented and discussed.

PMID- 15453534
TI  - Laryngeal amyloidosis: localized versus systemic disease and update on diagnosis
      and therapy.
AB  - The clinical and pathological characteristics, possibility of systemic disease,
      and effect of local therapy were studied in laryngeal amyloidosis. Records of all
      patients with localized laryngeal amyloidosis in a single tertiary referral
      center were examined retrospectively at diagnosis and after local therapy. Of 188
      new patients with amyloidosis between 1990 and 2003, 5 patients had localized
      laryngeal amyloidosis. A sixth patient with localized laryngeal amyloidosis
      turned out to have systemic AL (immunocyte-derived) amyloidosis 8 years later.
      Free light chains were found in this patient, as well as in 1 of the other 5
      patients. Amyloid interfering with laryngeal or airway function was removed
      during microlaryngoscopy with a carbon dioxide laser or cold endoscopic excision.
      The best results were seen when glottic deposits were removed by cold endoscopic
      excision, and supraglottic deposits by a carbon dioxide laser. Four patients had
      recurrent disease. A systematic workup, including measurement of free light
      chains, helps to rule out systemic disease.

PMID- 15453535
TI  - Locally advanced thyroid carcinoma.
AB  - Patients with locally advanced thyroid carcinoma were studied to document
      survival, posttreatment vocal cord function, and dysphagia. A retrospective
      medical record review collected patient data recorded, including age, gender, and
      tumor-specific data. The outcome data collected included vocal cord function,
      presence of a tracheotomy or feeding tube, and the presence or absence of
      dysphagia. I studied 95 patients with surgically managed thyroid cancer. Forty
      three patients had locally invasive disease and/or recurrent disease. During a
      median follow-up of 5 years, 18% of the patients with invasive cancer died of
      disease. The patients with completely resected invasive cancers had a
      significantly better survival rate than did the patients with microscopic
      residual disease. I conclude that complete resection of invasive disease provides
      a survival advantage and should be accomplished if speech and swallowing can be
      preserved. Most patients can obtain local control with minimal morbidity, and
      they rarely die of local disease.

PMID- 15453536
TI  - Surface electromyographic activity in total laryngectomy patients following
      laryngeal nerve transfer to neck strap muscles.
AB  - Hands-free triggering and pitch control would improve electrolarynx devices,
      which are inconvenient to use and sound unnatural. The present study tested the
      strategy of salvaging voice-related neural signals for hands-free electrolarynx
      control either by transferring cut recurrent laryngeal nerves (RLNs) to
      denervated neck strap muscles or by preserving strap muscles with their normal
      innervation. An RLN nerve transfer was performed at the time of total
      laryngectomy in 8 individuals, and in 5 of these subjects, strap muscles with
      intact ansa cervicalis innervation were also preserved for comparison. Neck
      surface electromyography performed over the strap muscles was used periodically
      for more than 1 year on phonatory and nonphonatory tasks. Signals were eventually
      obtained in all subjects from both RLN-innervated and ansa-innervated strap
      muscles that correlated with speech production. After 1 year, RLN-driven signals
      were larger than ansa-driven signals in magnitude, and their timing appeared
      better correlated with intended phonation. The results show that neck surface
      electromyography is an effective control source for hands-free electrolarynx
      activation, and that RLN transfer may provide the best approach for obtaining
      phonation-related activity.

PMID- 15453537
TI  - Apnea spells in an infant with vallecular cyst.

PMID- 15453538
TI  - Calming restless legs.

PMID- 15453539
TI  - Treatment of the obstructive sleep apnea/hypopnea syndrome: the effect on blood
      pressure.

PMID- 15453540
TI  - A piece of the surgical puzzle.

PMID- 15453541
TI  - On measurement consistency and other hobgoblins.

PMID- 15453542
TI  - The diurnal rhythm of hypocretin in young and old F344 rats.
AB  - STUDY OBJECTIVES: Hypocretins (HCRT-1 and HCRT-2), also known as orexins, are
      neuropeptides localized in neurons surrounding the perifornical region of the
      posterior hypothalamus. These neurons project to major arousal centers in the
      brain and are implicated in regulating wakefulness. In young rats and monkeys,
      levels of HCRT-1 are highest at the end of the wake-active period and lowest
      toward the end of the sleep period. However, the effects of age on the diurnal
      rhythm of HCRT-1 are not known. DESIGN: To provide such data, cerebrospinal fluid
      (CSF) was collected from the cisterna magna of young (2-month-old, n = 9), middle
      aged (12 months, n = 10), and old (24 months, n = 10) F344 rats at 4-hour
      intervals, (beginning at zeitgeber [ZT]0, lights on). CSF was collected once from
      each rat every 4 days at 1 ZT point. After collecting the CSF at all of the time
      points, the rats were kept awake by gentle handling for 8 hours (ZT 0-ZT8), and
      the CSF was collected again at the end of the sleep-deprivation procedure. HCRT-1
      levels in the CSF were determined by radioimmunoassay SETTINGS: Basic
      neuroscience research lab. MEASUREMENTS AND RESULTS: Old rats had significantly
      less HCRT-1 in the CSF versus young and middle-aged rats (P < .002) during the
      lights-on and lights-off periods and over the 24-hour period. In old rats,
      significantly low levels of HCRT-1 were evident at the end of the lights-off
      period (predominantly wake-active period). The old rats continued to have less
      HCRT-1 even after 8 hours of prolonged waking. Northern blot analysis did not
      show a difference in pre-proHCRT mRNA between age groups. CONCLUSIONS: In old
      rats there is a 10% decline in CSF HCRT-1 over the 24-hour period. Functionally,
      if there is less HCRT-1, which our findings indicated, and there is also a
      decline in HCRT receptor mRNA, as has been previously found, then the overall
      consequence would be diminished action of HCRT at target sites. This would
      diminish the waking drive, which in the elderly could contribute to the increased
      tendency to fall asleep during the normal wake period.

PMID- 15453543
TI  - Characterization of the sleep-wake patterns in mice lacking fatty acid amide
      hydrolase.
AB  - STUDY OBJECTIVES: Oleamide and anandamide are fatty acid amides implicated in the
      regulatory mechanisms of sleep processes. However, due to their prompt catabolism
      by fatty acid amide hydrolase (FAAH), their pharmacologic and behavioral effects,
      in vivo, disappear rapidly. To determine if, in the absence of FAAH, the
      hypnogenic fatty acid amides induce an increase of sleep, we characterized the
      sleep-wake patters in FAAH-knockout mice [FAAH (-/-)] before and after sleep
      deprivation. DESIGN: FAAH (-/-), FAAH (+/-), and FAAH (+/+) mice were implanted
      chronically for sleep, body temperature (Tb), and locomotor activity (LMA)
      recordings. Sleep-wake states were recorded during a 24-hour baseline session
      followed by 8 hours of sleep deprivation. Recovery recordings were done during
      the 16 hours following sleep deprivation. Total amount of wake, slow-wave sleep,
      and rapid eye movement sleep were calculated and compared between genotypes. The
      electroencephalographic spectral analysis was performed by fast Fourier transform
      analysis. Telemetry recordings of Tb and LMA were carried out continuously during
      4 days under baseline conditions. SETTING: N/A. PATIENTS OR PARTICIPANTS: FAAH (
      /-) mice and their heterozygote (+/-) and control (+/+) littermates were used.
      INTERVENTIONS: Sleep deprivation. MEASUREMENTS AND RESULTS: FAAH (-/-) mice
      possess higher values of slow-wave sleep and more intense episodes of slow-wave
      sleep than do control littermates under baseline conditions that are not related
      to differences in Tb and LMA. A rebound of slow-wave sleep and rapid eye movement
      sleep as well an increase in the levels of slow-wave activity were observed after
      sleep deprivation in all genotypes. CONCLUSION: These findings support the role
      of fatty acid amides as possible modulators of sleep and indicate that the
      homeostatic mechanisms of sleep in FAAH (-/-) mice are not disrupted.

PMID- 15453544
TI  - Prostaglandin D synthase (beta-trace) in healthy human sleep.
AB  - STUDY OBJECTIVES: The prostaglandin D system plays an important role in animal
      sleep. In humans, alterations in the prostaglandin D system have been found in
      diseases exhibiting sleep disturbances as a prominent symptom, such as
      trypanosoma infection, systemic mastocytosis, bacterial meningitis, major
      depression, or obstructive sleep apnea. Assessment of this system's activity in
      relation to human physiologic sleep was the target of the present study. DESIGN:
      Serum concentrations of lipocalin-type prostaglandin D synthase (L-PGDS, former
      beta-trace), and plasma levels of the pineal hormone melatonin were measured in
      20 healthy humans (10 women, 10 men; aged: 23.3 +/- 2.39 years) at 4-hour
      intervals over a period of 5 days and nights, which included physiologic sleep,
      rapid eye movement sleep deprivation, and total sleep deprivation. In addition,
      the serum L-PGDS and plasma melatonin levels of 6 subjects were determined under
      conditions of bright white (10,000 lux) or dark red light (< 50 lux) in a
      crossover design during total sleep deprivation. Nocturnal blood sampling was
      performed by a through-the-wall tube system. L-PGDS was measured by an automated
      immunonephelometric assay, and melatonin was analyzed by direct radioimmunoassay.
      RESULTS: Serum L-PGDS concentrations showed marked time-dependent changes with
      evening increases and the highest values at night (P < .0005). This nocturnal
      increase was suppressed during total sleep deprivation (P < .05), independent of
      external light conditions and melatonin secretion. Rapid eye movement sleep
      deprivation had no impact on circulating L-PGDS levels. CONCLUSIONS: The
      circadian L-PGDS pattern and its suppression by total sleep deprivation indicate
      an interaction of the prostaglandin D system and human sleep regulation. L-PGDS
      measurements may well provide new insights into physiologic and pathologic sleep
      regulation in humans.

PMID- 15453545
TI  - Reduction of transcallosal inhibition upon awakening from REM sleep in humans as
      assessed by transcranial magnetic stimulation.
AB  - STUDY OBJECTIVES: The aim of the study is to assess, in humans, transcallosal
      inhibition upon awakening from rapid eye movement (REM) and non-REM sleep, by
      paired-pulse transcranial magnetic stimulation (TMS). DESIGN: During the daytime,
      a baseline session of motor evoked potentials (MEPs) was recorded. During the
      nighttime, the TMS sessions were administered just before sleep onset and upon
      awakenings from REM and stage 2 sleep, both in the early and final part of night.
      SETTING: The sleep research laboratory at the University of Rome "La Sapienza."
      PARTICIPANTS: Ten right-handed subjects participated in the experiment for 4
      consecutive sleep-recording nights. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS:
      During the daytime, a robust transcallosal inhibition was found; the MEP
      amplitude reduction ranged from 35% to 40%. During the nighttime, a decrease of
      transcallosal inhibition from right-to-left motor cortex, as compared to that
      from left-to-right motor cortex, was observed. The direct assessment of MEP
      changes, as a function of sleep stage and of the time of night, pointed to a drop
      of transcallosal inhibition after awakening from REM sleep. Therefore, the
      inhibitory activity of transcallosal fibers observed after non-REM awakening
      almost disappeared after REM sleep awakenings. CONCLUSIONS: The drastic drop of
      transcallosal inhibition after awakenings from REM sleep represents the first
      evidence in humans of a change of interhemispheric connectivity mediated by the
      corpus callosum during this sleep stage and may open new avenues for a better
      understanding of some aspects of sleep mechanisms (ie, dreaming function and
      dream mentation).

PMID- 15453546
TI  - Risk-taking behavior: effects of ethanol, caffeine, and basal sleepiness.
AB  - STUDY OBJECTIVES: This study examined the effects of ethanol, caffeine, and basal
      sleepiness on a laboratory measure of risk-taking behavior, the Stop Light Task.
      The aims were to determine whether sleepiness and ethanol degrade psychomotor
      speed and risky choice and whether caffeine attenuates these effects. DESIGN:
      Mixed design with participants chosen for basal level of sleepiness and each
      assessed under 4 conditions presented in a Latin-square crossover design.
      PARTICIPANTS: Thirteen healthy adult volunteers aged 21 to 35 years.
      INTERVENTIONS: Participants received ethanol 0.5 g/kg and caffeine placebo,
      ethanol 0.5 g/kg and caffeine 150 mg, ethanol 0.5 g/kg and caffeine 300 mg, or a
      dual (ethanol-caffeine) placebo between 9:00 am and 9:30 am. MEASUREMENTS: The
      Multiple Sleep Latency Test (MSLT) was used to determine basal level of
      sleepiness. Subjects completed the Stop Light Task about 60 to 90 minutes after
      drug administration to assess psychomotor speed and risky choices. RESULTS: Seven
      subjects were classified as Alert (MSLT = 12.6 +/- 2.0 minutes) and 6 Sleepy
      (MSLT = 8.1 +/- 1.0 minutes). Sleepy compared to Alert subjects did not differ in
      psychomotor speed overall. Ethanol significantly slowed psychomotor speed
      relative to placebo, and ethanol-caffeine combinations attenuated this effect.
      Consistent with previous studies using the Stop Light Task, higher response
      requirements (FR15-FR50) and higher point loss probability (12.5%, 37.5%, 100%)
      significantly decreased risky choice, across sleepiness and treatment conditions.
      Alert subjects made "go" (primary measure of risk-taking) choices more often at
      lower response requirements and less often at higher response requirements,
      relative to Sleepy subjects. Ethanol did not significantly affect "go" choices
      but did produce changes in "go" choices as a function of response requirement.
      Given their more optimal pattern of choice behavior, Alert subjects gained
      significantly more money than Sleepy subjects; ethanol and caffeine combinations
      did not significantly affect money earned. CONCLUSIONS: These data suggest that
      sleepiness moderates risky choice such that Alert subjects have improved choice
      "acuity." Also, under conditions where risk-taking depends on responding rapidly
      (like the Stop Light Task), ethanol may also impair responding and caffeine may
      attenuate this effect.

PMID- 15453547
TI  - Hypnotic efficacy of zaleplon for daytime sleep in rested individuals.
AB  - STUDY OBJECTIVES: The primary objective of this study was to determine whether
      zaleplon (10 mg) effectively promoted sleep during the daytime in well-rested
      individuals when compared to placebo. A secondary objective was to see if, while
      not expected, the use of zaleplon impacted the performance of well-rested
      individuals upon awakening. DESIGN: Repeated measures with 2 within-subject
      factors: drug (placebo/zaleplon) and trial (hourly testing during waking hours).
      Polysomnographic variables were recorded during a 3.5-hour nap following drug
      administration. Performance measures and subjective reports were collected during
      every waking trial of each session. SETTING: The study was conducted at the
      Chronobiology and Sleep Laboratory located at Brooks Air Force Base.
      PARTICIPANTS: Twelve participants, 6 men and 6 women. INTERVENTIONS: 10-mg
      zaleplon or placebo capsules, single afternoon dose. Drug administration was
      counterbalanced and double-blinded. MEASUREMENTS AND RESULTS: Zaleplon allowed
      participants to obtain significantly more slow-wave sleep than under placebo.
      There was also a trend for participants under zaleplon to accomplish a greater
      amount of sleep than under placebo. Performance was not adversely impacted
      following a 3.5-hour daytime sleep under zaleplon, nor were any undesirable
      symptoms induced. CONCLUSIONS: Zaleplon improves sleep quality when used by
      rested individuals to accomplish daytime sleep.

PMID- 15453548
TI  - Effects of gamma-hydroxybutyrate (GHB) on vigilance states and EEG in mice.
AB  - STUDY OBJECTIVES: Gamma-hydroxybutyrate (GHB) is an endogenous neuromodulator
      that appears to have wide-ranging effects on vigilance and behavior. In the
      present study, we examined the effects of GHB on sleep-wake behavior and EEG in
      mice. In addition, we measured effects of GHB on body temperature and arousal or
      stress hormones. DESIGN: Adult male BALB/c mice were implanted with
      electroencephalographic and electromyographic electrodes to record vigilance
      states and an intraperitoneal transmitter to record body temperature. After
      recovery from surgery and habituation to the recording procedure, the mice were
      intraperitoneally injected with saline or GHB (50, 150 or 250 mg/kg) half an hour
      after light onset. Blood samples to measure effects of GHB on corticosterone and
      prolactin levels were collected in a separate group of mice. SETTING: N/A
      PATIENTS: N/A INTERVENTIONS: N/A RESULTS: At the lowest dose, GHB had no
      conspicuous effects on behavioral vigilance and electroencephalogram, nor on body
      temperature and endocrine measures. At the 2 higher doses, GHB induced a short
      period of electroencephalographic hypersynchrony in parallel to complete
      behavioral inactivity, an unnatural flat body posture, and nonresponsiveness to
      stimulation. After the highest dose of GHB, this state of reduced vigilance was
      associated with a decrease in body temperature, while prolactin and
      corticosterone levels were strongly increased. CONCLUSIONS: The results do not
      indicate a clear sleep-promoting effect of GHB in mice, but, at higher doses, it
      caused electroencephalographic hypersynchronization together with a coma-like
      state.

PMID- 15453549
TI  - Ropinirole decreases periodic leg movements and improves sleep parameters in
      patients with restless legs syndrome.
AB  - STUDY OBJECTIVES: Polysomnographic study evaluating the efficacy of ropinirole
      for the treatment of patients with restless legs syndrome (RLS) suffering from
      periodic leg movements in sleep (PLMS). DESIGN: Double-blinded, placebo
      controlled, parallel-group study. SETTING: 15 tertiary referral centers in the
      USA. PARTICIPANTS: 65 patients with RLS and PLMS. INTERVENTIONS: Ropinirole (0.25
      4.0 mg per day) or placebo for 12 weeks. MEASUREMENTS AND RESULTS: Data from 59
      patients were included in the primary endpoint analysis. PLMS per hour decreased
      more with ropinirole (48.5 to 11.8), compared with placebo (35.7 to 34.2;
      adjusted treatment difference: -27.2; 95% confidence interval [CI]: -39.1, -15.4;
      P < .0001). Periodic limb movements with arousal per hour decreased from 7.0 to
      2.5 with ropinirole but increased from 4.2 to 6.0 with placebo (adjusted
      treatment difference: -4.3, 95% CI: -7.6, -1.1; P = .0096). Periodic limb
      movements while awake per hour decreased from 56.5 to 23.6 with ropinirole but
      increased from 46.6 to 56.1 with placebo (adjusted treatment difference: -39.5;
      95% CI: -56.9, -22.1; P < .0001). Ropinirole treatment significantly improved
      patients' ability to initiate sleep (P < .05) and the amount of Stage 2 sleep
      compared with placebo (P < .001). There were also non-significant trends toward
      increases in total sleep time and sleep efficiency. Sleep adequacy (measured on
      the subjective Medical Outcomes Study sleep scale) was significantly improved
      with ropinirole treatment (adjusted treatment difference: 12.1; 95% CI: 1.1,
      23.1; P = .0316). In contrast, the placebo group showed a greater increase in
      Stage 3/4 sleep (P < .01). No serious adverse events occurred in either group.
      CONCLUSIONS: Ropinirole is effective in the treatment of both the sleep and
      waking symptoms of RLS.

PMID- 15453550
TI  - Genetic and environmental influences in sleep-disordered breathing in older male
      twins.
AB  - STUDY OBJECTIVES: To estimate the extent to which genetic factors contribute to
      the variation in several indices of sleep-disordered breathing in elderly male
      twins. DESIGN AND SETTING: A biometric genetic study based on data from
      unattended Edentrace recordings in a sample of elderly male twins. PARTICIPANTS:
      122 World War II male veteran twin pairs, including 68 monozygotic pairs aged
      78.9 (+/- 2.7) years and 54 dizygotic pairs aged 78.4 (+/- 2.4) years.
      INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: The average (+/- SD) respiratory
      disturbance index for this sample was 17.2 +/- 14.5, the average (+/- SD) oxygen
      desaturation index was 18.8 +/- 16.4, and the average (+/- SD) minimum SaO2 level
      was 79.6 +/- 8.1%. Intraclass twin-pair correlations for log-transformed
      respiratory disturbance index were 0.59 in monozygotic pairs and 0.36 in
      dizygotic pairs. For oxygen desaturation index, intraclass correlations were 0.44
      in monozygotic pairs and 0.24 in dizygotic pairs. For minimum SaO2, intraclass
      correlations were 0.38 and 0.11, respectively. Maximum likelihood estimates of
      heritability with associated 95% confidence intervals were 37% [22%, 52%] for
      respiratory disturbance index, 36% [19%, 53%] for oxygen desaturation index, and
      10% [0%, 30%] for minimum SaO2. Adjustments of sleep-disordered breathing
      measures for age, body mass index, and waist and neck circumference had minimal
      effect on estimates of heritability. CONCLUSIONS: The present data indicate that
      sleep-disordered breathing, even in old age, is determined, in part, by genetic
      factors.

PMID- 15453551
TI  - Using a wrist-worn device based on peripheral arterial tonometry to diagnose
      obstructive sleep apnea: in-laboratory and ambulatory validation.
AB  - STUDY OBJECTIVES: To assess the accuracy of a wrist-worn device (Watch_PAT 100)
      to diagnose obstructive sleep apnea in the home. DESIGN: Participants completed 2
      overnight diagnostic studies with the test device: 1 night in the laboratory with
      concurrent polysomnography and 1 night in the home with only the Watch_PAT. The
      order of the laboratory and home study nights was random. The frequency of
      respiratory events on the PSG was quantified using indexes based on 2 definitions
      of hypopnea: the respiratory disturbance index (RDI) using American Academy of
      Sleep Medicine Task Force criteria for clinical research, also referred to as the
      Chicago criteria (RDI.C), and the Medicare guidelines (RDI.M). The Watch_PAT RDI
      (PAT RDI) and oxygen desaturation index (PAT ODI) were then evaluated against the
      polysomnography RDI.C and RDI.M, respectively, for both Watch_PAT diagnostic
      nights, yielding IN-LAB and HOME-LAB comparisons. SETTING: Sleep laboratory
      affiliated with a tertiary-care academic medical center. PATIENTS: 30 patients
      referred with suspected OSA. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: The
      polysomnography and PAT measures were compared using the mean [2 SD] of the
      differences and the intra-class correlation coefficient (ICC). The receiver
      operator characteristic curve was used to assess optimum sensitivity and
      specificity and calculate likelihood ratios. For the IN-LAB comparison, there was
      high concordance between RDI.C and PAT RDI (ICC = 0.88, mean difference 2.5
      [18.9] events per hour); RDI.M and PAT ODI (ICC = 0.95, mean difference 1.4
      [12.9] events per hour; and sleep time (ICC = 0.70, mean difference 7.0 [93.1]
      minutes) between the test device and PSG. For the HOME-LAB comparison, there was
      good concordance between RDI.C and PAT RDI (ICC = 0.72, mean difference 1.4
      [30.1] events per hour) and RDI.M and PAT ODI (ICC = 0.80, mean difference 1.6
      [26.4] events per hour) for the test device and PSG. Home studies were performed
      with no technical failures. CONCLUSIONS: In a population of patients suspected of
      having obstructive sleep apnea, the Watch_PAT can quantify an ODI that compares
      very well with Medicare criteria for defining respiratory events and an RDI that
      compares favorably with Chicago criteria for defining respiratory events. The
      device can be used with a low failure rate for single use in the lab and home for
      self-administered testing.

PMID- 15453552
TI  - Oral appliance therapy reduces blood pressure in obstructive sleep apnea: a
      randomized, controlled trial.
AB  - STUDY OBJECTIVE: To investigate the short-term effect (4 weeks) of oral appliance
      therapy for obstructive sleep apnea on blood pressure. DESIGN: Randomized,
      controlled, crossover trial. SETTING: Multidisciplinary sleep disorders clinic in
      a university teaching hospital. PATIENTS: Sixty-one patients diagnosed with
      obstructive sleep apnea on polysomnography (apnea hypopnea index > or = 10 per
      hour and at least 2 of the following symptoms--daytime sleepiness, snoring,
      witnessed apneas, fragmented sleep; age > 20 years; and minimum mandibular
      protrusion of 3 mm). INTERVENTION: A mandibular advancement splint (MAS) and
      control oral appliance for 4 weeks each. MEASUREMENTS AND RESULTS:
      Polysomnography and 24-hour ambulatory blood pressure monitoring were carried out
      at baseline and following each 4-week intervention period. Patients showed a 50%
      reduction in mean apnea hypopnea index with MAS compared with the control and a
      significant improvement in both minimum oxygen saturation and arousal index.
      There was a significant reduction with the MAS in mean (+/- SEM) 24-hour
      diastolic blood pressure (1.8 +/- 0.5 mmHg) compared with the control (P = .001)
      but not in 24-hour systolic blood pressure. Awake blood-pressure variables were
      reduced with the MAS by an estimated mean (+/- SEM) of 3.3 +/- 1.1 mmHg for
      systolic blood pressure (P = .003) and 3.4 +/- 0.9 mmHg for diastolic blood
      pressure (P < .0001). There was no significant difference in blood pressure
      measured asleep. CONCLUSION: Oral appliance therapy for obstructive sleep apnea
      over 4 weeks results in a reduction in blood pressure, similar to that reported
      with continuous positive airway pressure therapy.

PMID- 15453553
TI  - Lateral pharyngoplasty versus uvulopalatopharyngoplasty: a clinical,
      polysomnographic and computed tomography measurement comparison.
AB  - STUDY OBJECTIVE: To compare the lateral pharyngoplasty procedure with
      uvulopalatopharyngoplasty (UPPP) in the treatment of obstructive sleep apnea
      hypopnea syndrome (OSAHS). DESIGN: Prospective randomized study. SETTING:
      Academic tertiary center. PATIENTS: Twenty-seven adults with OSAHS originally
      selected for treatment with UPPP. INTERVENTIONS: Patients were randomly assigned
      to 2 groups: in one group, we performed the lateral pharyngoplasty (15 cases),
      and in the other, we did the UPPP (12 cases). MEASUREMENTS AND RESULTS: We
      compared treatment outcomes through the evaluation of OSAHS-related symptoms and
      the analysis of polysomnographic tests and computed tomography measurements of
      pharyngeal airway. The lateral pharyngoplasty group achieved a statistically
      greater reduction in body weight, excessive daytime sleepiness, and apnea
      hypopnea index. In addition, only in this group did we observe a statistically
      significant increase in the amount of deep sleep stages and improvement in
      morning headaches. Patients from the UPPP group did not present significant
      changes in the polysomnographic parameters. Pharyngeal airway measurement
      outcomes were similar in both groups and did not reflect the clinical and
      polysomnographic differences we observed. CONCLUSIONS: Lateral pharyngoplasty
      produces better clinical and polysomnographic outcomes in the treatment of OSAHS
      than does UPPP, without resultant differences in the cross-sectional measurements
      of the pharyngeal airway between these treatments.

PMID- 15453554
TI  - Validation of a new system of tracheal sound analysis for the diagnosis of sleep
      apnea-hypopnea syndrome.
AB  - STUDY OBJECTIVES: To evaluate the validity of a novel method of using tracheal
      sound analysis for the diagnosis of sleep apnea-hypopnea syndrome. DESIGN:
      Retrospective analysis in consecutive patients. SETTING: A sleep clinic in a
      general hospital. PATIENTS: A total of 383 patients who were referred for
      suspected sleep apnea-hypopnea syndrome and underwent diagnostic polysomnography
      with sufficient quality. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Ordinary
      polysomnography with simultaneous tracheal sound recording was performed. The
      apnea-hypopnea index (AHI) was calculated as the number of apnea and hypopnea
      events per hour of sleep. Tracheal sounds were digitized and recorded as power
      spectra. An automated computer program detected transient falls (TS-dip) in the
      time series of moving average of the logarithmic power of tracheal sound. We
      defined the tracheal sound-respiratory disturbance index (TS-RDI) as the number
      of TS-dips per hour of examination. We also calculated the oxygen desaturation
      index (the number of SaO2 dips of at least 4% per hour of examination). The TS
      RDI highly correlated with AHI (r = 0.93). The mean (+/- SD) difference between
      the TS-RDI and AHI was -8.4 +/- 10.4. The diagnostic sensitivity and specificity
      of the TS-RDI when the same cutoff value was used as for AHI were 93% and 67% for
      the AHI cutoff value of 5 and 79% and 95% for the AHI cutoff value of 15. The
      agreement between the TS-RDI and AHI was better than that between the oxygen
      desaturation index and AHI. CONCLUSIONS: The fully automated tracheal sound
      analysis demonstrated a relatively high performance in the diagnosis of sleep
      apnea-hypopnea syndrome. We think that this method is useful for the portable
      monitoring of sleep apnea-hypopnea syndrome.

PMID- 15453555
TI  - Mandibular dimensions in children with obstructive sleep apnea syndrome.
AB  - OBJECTIVE: We hypothesized that mandibular size may play a role in the etiology
      of obstructive sleep apnea syndrome (OSAS) in children, since a smaller mandible
      may reduce airway size. We used magnetic resonance imaging to determine the
      mandible dimensions of children with OSAS. DESIGN: Case control study. SETTING:
      Tertiary-care pediatric hospital. PARTICIPANTS: Twenty-four subjects (mean age
      4.9 +/- 1.7 years) with mild to moderate OSAS (Apnea Index 3.5 +/- 5.1), and 24
      matched controls (mean age 4.9 +/- 1.8 years). INTERVENTION: Magnetic resonance
      imaging of the upper airway under sedation. MEASUREMENTS: Eight measurements were
      obtained from a 3-dimensional segmentation of the mandible using 3DVIEWNIX
      software. Measurements included length, height, width, midsymphysis menti angle,
      angle of mandible, enclosure area, surface area, and volume. Descriptive
      comparisons using Student t test and multivariate analyses of variance were
      performed. RESULTS: Individual measurement comparisons revealed no significant
      differences between groups. Multivariate analysis showed a lower bound of a 95%
      confidence interval for an effect size measure for "general mandibular size,"
      including all 6 linear, the area, and the volume measurements, to be -0.25.
      CONCLUSION: Our study shows that a smaller mandible is not a feature in children
      with OSAS who do not have apparent craniofacial abnormalities.

PMID- 15453556
TI  - Daytime sleepiness and alertness in patients with Parkinson disease.
AB  - STUDY OBJECTIVES: The goal of the study was to objectively measure daytime
      sleepiness and alertness in patients undergoing treatment for idiopathic
      Parkinson disease (PD) and assess potential contributing factors. DESIGN:
      Prospective study. SETTING: An accredited sleep disorders center in a university
      based medical center in a large urban area. PATIENTS: Twenty consecutive subjects
      with idiopathic PD were recruited from a tertiary-care movement disorders clinic.
      INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Patients underwent polysomnography,
      with a Multiple Sleep Latency Test (MSLT) and a Maintenance of Wakefulness Test
      (MWT) on the following day. Forty-seven percent of the sample was pathologically
      sleepy according to the MSLT, but only 26% had abnormal MWT scores. There was
      also a different pattern of correlations between predictors of sleepiness and
      MSLT and MWT scores. Percentage of stage 1 sleep had the largest correlation with
      MSLT (-0.42), while pergolide equivalents had the largest correlation with MWT (
      0.70). CONCLUSIONS: In this sample of subjects with PD, severe daytime sleepiness
      was common and was related to poor sleep quality. Daytime alertness as measured
      by the MWT was impaired as medication burden increased.

PMID- 15453557
TI  - Subjective and objective sleepiness in monozygotic twins discordant for chronic
      fatigue syndrome.
AB  - STUDY OBJECTIVE: To examine the association of chronic fatigue syndrome (CFS)
      with measures of objective and subjective sleepiness. DESIGN: Monozygotic co-twin
      control study. SETTING: Academic medical center. PATIENTS AND PARTICIPANTS:
      Twenty monozygotic twin pairs discordant for CFS. INTERVENTIONS: N/A.
      MEASUREMENTS AND RESULTS: All twins completed an Epworth Sleepiness Scale (ESS),
      4 Stanford Sleepiness Scales (SSS), and underwent a standard 4-nap multiple sleep
      latency test. We compared the ESS scores, average SSS scores, and average sleep
      latency in CFS and healthy twins. The CFS twins reported more sleepiness as
      measured by mean scores on the ESS (10.9 vs 8.2; 95% confidence interval [CI] =
      0.3-5.5; P = .03) and the SSS (3.4 versus 2.1; 95% CI = 0.7-1.9; P < .001). The
      mean sleep latency on the Multiple Sleep Latency Test was not significantly
      different between the CFS and healthy twins (8.9 vs 10.0 minutes; 95% CI -4.4
      1.7; P = .33). Mean SSS scores increased among the CFS twins and decreased among
      healthy twins from nap 1 to nap 4 (P < .001). The individual ESS scores and mean
      sleep latencies on the Multiple Sleep Latency Test were negatively correlated for
      all the twins (Pearson's r = - 0.40; P = .01), with a slightly stronger
      association among the healthy twins (Pearson's r = -0.42, P = .07) than the CFS
      twins (Pearson's r = -0.36, P = .15). CONCLUSIONS: CFS twins reported
      significantly more subjective sleepiness than their healthy co-twins despite
      similar nonpathologic mean sleep latencies on the Multiple Sleep Latency Test.
      Patients with CFS may mistake their chronic disabling fatigue for sleepiness.

PMID- 15453558
TI  - An epidemiologic study of self-reported sleep problems among Japanese
      adolescents.
AB  - STUDY OBJECTIVE: To examine the prevalence and correlates of sleep problems in
      Japanese adolescents. DESIGN AND SETTING: The survey was designed as a cross
      sectional sampling. The targets of the survey were junior and senior high schools
      throughout Japan. Sample schools were selected by stratified cluster sampling.
      Self-reported anonymous questionnaires were sent to sample schools for all
      students to fill out. PARTICIPANTS: A total of 107,907 adolescents responded, and
      106,297 questionnaires were subjected to analysis. MEASUREMENTS AND RESULTS: The
      overall prevalences of sleep problems in the month preceding the questionnaire
      were difficulty initiating sleep (boys: 15.3%, girls: 16.0%); nocturnal sleep
      duration less than 6 hours (boys: 28.7%, girls: 32.6%); excessive daytime
      sleepiness (boys: 33.3%, girls: 39.2%), and subjectively insufficient sleep
      (boys: 38.1%, girls: 39.0%). Multiple logistic regression analysis showed that
      female sex, being a senior high-school student, and having an unhealthy lifestyle
      (psychological stress, smoking, and drinking alcohol) were risk factors for sleep
      problems. CONCLUSION: Self-reported sleep problems in Japanese adolescents were
      common and were associated with multiple factors. There is a need for health
      education directed at solving sleep problems in Japanese adolescents.

PMID- 15453559
TI  - The measurement of sleep by actigraphy: direct comparison of 2 commercially
      available actigraphs in a nonclinical population.
AB  - STUDY OBJECTIVES: To compare 2 commercially available actigraphs. DESIGN:
      Subjects wore the Actiwatch L and the Basic Mini-Motionlogger for 2 nights.
      SETTING: Naturalistic. PARTICIPANTS: 20 healthcare workers aged 24 to 64 years.
      MEASUREMENTS: Measures included sleep latency, total sleep time, wake after sleep
      onset, and sleep efficiency. Actiwatch L data were analyzed at 3 sensitivity
      settings. RESULTS: The Mini-Motionlogger reported more total sleep time, less
      wake after sleep onset, and greater sleep efficiency than the Actiwatch L set at
      high sensitivity. It also reported more wake after sleep onset than the Actiwatch
      L set at low sensitivity. CONCLUSIONS: Both devices achieved similar overall
      performance when the Actiwatch L was set at medium sensitivity.

PMID- 15453560
TI  - The effect of measurement unreliability on sleep and respiratory variables.
AB  - INTRODUCTION: Unreliability associated with scoring sleep variables is a
      potentially problematic issue in clinical and research studies. When scoring
      unreliability is unrecognized, it can contribute to the following: increase
      variability in the measures of interest, decrease a study's ability to detect
      important relationships, attenuate correlation coefficients, and increase
      clinical trial costs. METHODS: This paper first models the relationship between
      scoring variability and reliability in commonly studied sleep variables. The
      paper then models the relationship between unreliability and sample size
      requirements and statistical power. Standard methods are used to model
      reliability using the intraclass correlation coefficient. RESULTS: The analysis
      shows that when scoring unreliability is minimized (i.e., scoring reliability is
      maximized), correlation coefficients are more robust, sample size requirements
      are reduced, statistical power is increased, and clinical trial costs are
      reduced. DISCUSSION: When scoring unreliability is recognized, research studies
      can compensate by increasing the number of research subjects studied; however, it
      is at the cost of increasing the costs of research and exposing greater numbers
      of subjects to possible study risks. An effective solution is to implement
      rigorous initial and ongoing training efforts to maintain high inter-rater and
      intra-rater reliability coefficients.

PMID- 15453561
TI  - Pathophysiology of upper airway obstruction: a developmental perspective.
AB  - The obstructive sleep apnea syndrome (OSAS) occurs in patients of all ages, from
      the premature infant to the elderly. Much remains unknown about the
      pathophysiology of the syndrome. However, research suggests that OSAS in all age
      groups is due to a combination of both anatomic airway narrowing and abnormal
      upper airway neuromotor tone. The anatomic predisposing factors for OSAS differ
      over the lifespan. However, a smaller upper airway is noted in all age groups and
      probably predisposes to airway collapse during sleep. Despite the known anatomic
      factors, such as craniofacial anomalies, obesity, and adenotonsillar hypertrophy,
      that contribute to OSAS throughout life, a clear anatomic factor cannot always be
      identified. This suggests that alterations in upper airway neuromotor tone also
      play an important role in the etiology of OSAS. Infants and children are less
      likely than adults to arouse in response to upper airway obstruction and do not
      compensate for prolonged increases in inspiratory resistive load. The overall
      ventilatory drive is probably normal in patients of all ages with OSAS. However,
      upper airway neuromotor tone and reflexes during sleep vary with age and are
      increased in normal infants and children compared to adults, perhaps as a
      compensatory response for their relatively narrow airway. This compensatory
      response appears to be blunted in children with OSAS. Further research is needed
      to fully understand the complexities of upper airway structure and function
      during both normal development and disease.

PMID- 15453562
TI  - Hypnotic medication: shed light not heat!

PMID- 15453563
TI  - The use of the dopamine-receptor partial agonist aripiprazole in the treatment of
      restless legs syndrome.

PMID- 15453564
TI  - Obesity is an important risk factor for sleep disordered breathing in children
      with Down syndrome.

PMID- 15453565
TI  - Tongue-muscle training by intraoral electrical neurostimulation is not a
      treatment option for sleep-disordered breathing.

PMID- 15453566
TI  - Optimizing sedation and analgesia in mechanically ventilated patients--an
      evidence-based approach.
AB  - Critically ill, mechanically ventilated patients experience pain and anxiety
      related to a number of factors, including underlying disease processes, invasive
      procedures, therapeutic devices, immobility, and even routine nursing care such
      as turning and positioning. Failure to provide adequate analgesia and sedation
      has been shown to have detrimental physiological consequences, including an
      increase in sympathetic nervous activity and ventilator dyssynchrony (Young,
      Knudsen, Hilton & Reves, 2000). Over-sedation has also given rise to concerns
      related to prolongation of mechanical ventilation, intensive care unit (ICU)
      length of stay, and cost. The challenge for the ICU team is to provide comfort
      while avoiding the consequences of both over- and under-sedation. New strategies
      show promise and focus on a team approach for the management of sedation and
      analgesia in critically ill, mechanically ventilated patients. These strategies
      include the use of sedation protocols, which incorporate nurse-driven dose
      titration directives, sedation scoring systems, and daily interruption of
      sedative infusions. This article provides a review of three recent studies
      evaluating these new approaches to the administration of sedation and analgesia
      in the adult ICU.

PMID- 15453567
TI  - I'm trying to heal...noise levels in a pediatric intensive care unit.
AB  - The literature demonstrates clearly that most intensive care units exceed the
      standard recommendations for noise levels in hospitals, and that high noise
      levels have negative impacts on patients and staff. The purpose of this study was
      to evaluate the level of noise in a PICU and compare it to the recommendations of
      international bodies. We outline recommendations to promote the awareness of this
      problem and suggest strategies to decrease the level of noise in a PICU. The
      orientations of these strategies are threefold: 1) architectural-acoustic design,
      2) equipment design and, most importantly, 3) staff education.

PMID- 15453568
TI  - A study of a complex ARDS patient.
AB  - With a high percentage of ICU patients suffering from ARDS from a direct or
      indirect lung injury, successful therapy and treatment modalities are important
      for all of us to know. It is our hope, as critical care professionals, to assist
      the patient through the course of this complication and prevent further lung
      injury related to the increasing oxygen demands, high positive pressure
      ventilation, and high volumes. When traditional methods of improving ventilation
      fail, we do have the options of proning our patients and/or trying high frequency
      oscillating ventilation to optimize oxygen exchange. The authors outline the
      course of events surrounding the care of a young patient with ARDS over 44 days
      in ICU. Proning, high frequency ventilation, and the use of steroids played a
      role in the recovery of Mr. M. Aggressive nursing care helped minimize the
      complications from these treatments and aided in the psychosocial aspects of a
      challenging family dynamic.

PMID- 15453569
TI  - [Molecular epidemiology and human genome project].

PMID- 15453570
TI  - Ascophyllum nodosum supplementation: a preharvest intervention for reducing
      Escherichia coli O157:H7 and Salmonella spp. in feedlot steers.
AB  - Ascophyllum nodosum (Tasco-14) decreased the prevalence of enterohemorrhagic
      Escherichia coli (EHEC) O157:H7 in animals fed prior to harvest. Tasco-14 was
      supplemented on a 2% dry matter basis 14 days prior to harvest to determine its
      effects on EHEC and Salmonella spp. prevalence. Two hundred mixed crossbred
      steers and heifers (Bos indicus x Bos taurus), in a large commercial finishing
      facility, served as experimental units. Treatment (TRT, n = 100) animals received
      a steam-rolled corn-based diet containing 2% Tasco-14 on a dry matter basis, and
      control (CON, n = 100) animals received only the steam-rolled corn-based diet.
      Hide swabs and fecal samples were obtained for EHEC and Salmonella spp.
      evaluations. Animals were sampled 1 day prior to (d - 1) the feeding of Tasco-14
      and immediately following exsanguinations. The prevalence of EHEC O157 on hide
      swabs and in fecal samples (P = 0.0001 and P < 0.0001, respectively) and the
      prevalence of EHEC O157:H7 on hide swabs and in fecal samples (P < 0.0001 and P <
      0.0001, respectively) was reduced by 33 and 36% from d - 1 levels on TRT hide
      swabs and by 9 and 11% in TRT fecal samples. The prevalence of EHEC O157 and EHEC
      O157:H7 was reduced by 33 and 36% from d - 1 levels on TRT hide swabs and by 9
      and 11% in TRT fecal samples. The prevalence of Salmonella spp. on hide swabs did
      not change for TRT animals (P = 0.64). CON animals showed an increase in
      Salmonella spp. prevalence (P < 0.0001) from d - 1 feeding levels on hide swabs.
      The prevalence of Salmonella spp. increased in both TRT and CON fecal samples
      when compared to d - 1 levels (P = 0.002). However, TRT samples exhibited a lower
      (P < 0.05) postfeeding prevalence of Salmonella spp. in fecal samples than did
      CON samples. Results from this study indicate that 2% Tasco-14 supplementation in
      feedlot cattle diets reduces EHEC O157 and EHEC O157:H7 prevalence on hide swabs
      and in fecal samples and may suppress increases in Salmonella spp.

PMID- 15453571
TI  - Effect of prechill fecal contamination on numbers of bacteria recovered from
      broiler chicken carcasses before and after immersion chilling.
AB  - Paired carcass halves were used to test whether fecal contamination of skin
      during processing of broiler chickens can be detected by increased bacterial
      counts in samples taken before and after immersion chilling. In each of three
      trials, six freshly defeathered and eviscerated carcasses were cut in half, and a
      rectangle (3 by 5 cm) was marked with dots of ink on the breast skin of each
      half. One half of each pair was chosen randomly, and 0.1 g of freshly collected
      feces was spread over the rectangle with a spatula. After 10 min, both halves
      were sprayed with tap water for 10 to 15 s until feces could no longer be seen in
      the marked area. Both halves were sampled with a 1-min carcass rinse and were
      then put in a paddle chiller with other eviscerated carcasses for 45 min to
      simulate industrial immersion chilling. Immediately after chilling, each carcass
      half was subjected to another 1-min rinse, after which the skin within the
      rectangle was aseptically removed from the carcass halves and stomached. Rinses
      of fecally contaminated halves had significantly higher Enterobacteriaceae
      immediately before chilling, but there were no differences in coliform and
      Escherichia coli counts. After chilling, there were no differences in
      Enterobacteriaceae, coliform, and E. coli counts in rinse or skin samples from
      the paired carcass halves. Correlations were generally poor between counts in
      rinse and skin samples but were significant between prechill and postchill rinses
      for both control and fecally contaminated halves. Correlations were also
      significant between counts in rinses of control and contaminated halves of the
      same carcass after chilling. Bacterial counts in postchill carcass rinses did not
      indicate that fecal contamination occurred before chilling.

PMID- 15453572
TI  - Prevalence and number of Salmonella in irish retail pork sausages.
AB  - A national Salmonella control program in the pork industry was enacted in Ireland
      in August 2002. This study was undertaken as part of a larger project
      investigating the role of pork as a source of human salmonellosis in Ireland. The
      objective of this survey was to assess the prevalence of Salmonella in Irish pork
      sausage at retail level. Samples, comprising branded prepacked sausages and loose
      sausages from supermarket meat counters and butcher shops, were collected from
      selected retail sites in four cities from October to December 2001 and from June
      to August 2002. A three-tube most-probable-number method was used to enumerate
      Salmonella in a selected number of samples that were positive by enrichment.
      Salmonella serotypes were detected in 4.4 and 1.7% of samples at each of the
      respective sampling periods, a level similar to those reported in other U.S. and
      U.K. studies. Isolates were characterized by serotype, phage type, and
      antimicrobial susceptibility. Eighteen (70%) were resistant to at least one
      antimicrobial, and 15 (58%) were resistant to four or more antimicrobials. Most
      of the isolates exhibited resistance to tetracycline. Five different phage types
      were detected. DT104 was the predominant phage type among Salmonella Typhimurium
      isolates. This study revealed that multidrug-resistant salmonellae are present in
      a proportion of Irish sausages and that further risk analysis work is necessary
      in order to quantify the risk posed to public health.

PMID- 15453573
TI  - Effect of spices and organic acids on the growth of Clostridium perfringens
      during cooling of cooked ground beef.
AB  - This study evaluated the effect of organic acids and spices, alone or combined,
      on Clostridium perfringens growth in cooked ground beef during alternative
      cooling procedures. Ground beef was inoculated with a three-strain cocktail of C.
      perfringens (ATCC 10388, NCTC 8238, and NCTC 8239) at 2 log spores per g and
      prepared following an industrial recipe (10% water, 1.5% sodium chloride, and
      0.5% sodium triphosphate [wt/wt]). Treatments consisted of the base meat plus
      combinations of commercial solutions of sodium lactate or sodium citrate (0 or
      2%, wt/wt) with chili, garlic and herbs, curry, oregano, or clove in commercial
      powder form (0 or 1%, wt/wt). Untreated meat was used as a control. Vacuum
      packaged samples of each treatment were cooked (75 degrees C for 20 min) and
      cooled from 54.4 to 7.2 degrees C in 15, 18, or 21 h. Spore counts were estimated
      after inoculation, cooking, and cooling. All treatments containing sodium citrate
      reduced the population of C. perfringens about 0.38 to 1.14 log units during each
      of the three cooling procedures. No sodium citrate and spice treatment
      combinations showed antagonisms or synergisms. Regardless of the cooling time,
      the control ground beef or treatments with any of the five spices alone supported
      C. perfringens growth above the U.S. Department of Agriculture stabilization
      guidelines of 1 log unit. Except for the 21-h cooling period, addition of sodium
      lactate prevented C. perfringens growth over 1 log unit. Depending on the cooling
      time and spice, some combinations of sodium lactate and spice kept C. perfringens
      growth below 1 log unit.

PMID- 15453574
TI  - Inactivation of Listeria innocua in nisin-treated salmon (Oncorhynchus keta) and
      sturgeon (Acipenser transmontanus) caviar heated by radio frequency.
AB  - Recent regulatory concerns about the presence of the pathogen Listeria
      monocytogenes in ready-to-eat aquatic foods such as caviar has prompted the
      development of postpackaging pasteurization processes. However, caviar is heat
      labile, and conventional pasteurization processes affect the texture, color, and
      flavor of these foods negatively. In this study, chum salmon (Oncorhynchus keta,
      2.5% total salt) caviar or ikura and sturgeon (Acipenser transmontanus, 3.5%
      total salt) caviar were inoculated with three strains of Listeria innocua in
      stationary phase at a level of more than 10(7) CFU/g. L innocua strains were used
      because they exhibit an equivalent response to L monocytogenes for many
      physicochemical processing treatments, including heat treatment. The products
      were treated by immersion in 500 IU/ml nisin solution and heat processed (an 8-D
      process without nisin or a 4-D process with 500 IU/ml nisin) in a newly developed
      radio frequency (RF; 27 MHz) heating method at 60, 63, and 65 degrees C. RF
      heating along with nisin acted synergistically to inactivate L. innocua cells and
      total mesophilic microorganisms. In the RF-nisin treatment at 65 degrees C, no
      surviving L. innocua microbes were recovered in sturgeon caviar or ikura. The
      come-up times in the RF-heated product were significantly lower compared with the
      water bath-heated caviar at all treatment temperatures. The visual quality of the
      caviar products treated by RF with or without nisin was comparable to the
      untreated control.

PMID- 15453575
TI  - Combining pediocin (ALTA 2341) with postpackaging thermal pasteurization for
      control of Listeria monocytogenes on frankfurters.
AB  - Frankfurters packaged in 1-link, 5-link, or 10-link packages were surface
      inoculated with a five-strain mixture of Listeria monocytogenes (3.40 or 5.20 log
      CFU/g) after treatments with 3,000 arbitrary units (AU) or 6,000 AU pediocin (in
      ALTA 2341) per link. The frankfurters were vacuum packaged, after which the
      packages were heated in hot water at 71, 81, or 96 degrees C for 30, 60, or 120
      s. L. monocytogenes was enumerated following the treatments. Selected treatments
      were subsequently evaluated during storage at 4, 10, and 25 degrees C for up to
      12 weeks. L. monocytogenes was reduced by all treatments, but 81 degrees C or
      more for at least 60 s in combination with pediocin (Pdn-6000) was necessary to
      achieve a 50% reduction of initial inoculations. Heat treatments were most
      effective for 1-link packages and least effective for 10-link packages. Little or
      no growth of L. monocytogenes occurred on frankfurters for 12 weeks at 4 or 10
      degrees C, and for 12 days at 25 degrees C. Generally, the treatments mentioned
      above did not significantly (P > 0.05) affect the sensory qualities of
      frankfurters. Therefore, pediocin (in ALTA 2341) in combination with
      postpackaging thermal treatment offers an effective treatment combination for
      improved control of L. monocytogenes on frankfurters.

PMID- 15453576
TI  - Combining pediocin with postpackaging irradiation for control of Listeria
      monocytogenes on frankfurters.
AB  - Frankfurters, in 1-link, 5-link, or 10-link packages, were surface inoculated
      with a five-strain mixture of Listeria monocytogenes (3.40 or 5.20 log CFU/g)
      after treatment with 3,000 arbitrary units (AU) or 6,000 AU of pediocin (in ALTA
      2341) per link. The frankfurters were vacuum packaged, after which the 1-link and
      5-link packages were irradiated at 1.2 or 2.3 kGy and the 10-link packages were
      irradiated at 1.4 or 3.5 kGy. L. monocytogenes was enumerated following the
      treatments. Selected treatments were subsequently evaluated during storage at 4,
      10, and 25 degrees C for up to 12 weeks. Combination of pediocin with
      postpackaging irradiation at 1.2 kGy or more was necessary to achieve a 50%
      reduction of L. monocytogenes on frankfurters in 1-link or 5-link packages. The
      combination of 6,000 AU of pediocin and irradiation at 2.3 kGy or more was
      effective in all package sizes for inhibition of the pathogen for 12 weeks at 4
      or 10 degrees C. There was a synergistic effect between pediocin and irradiation
      for inhibition of L. monocytogenes. Storage at 4 degrees C enhanced the
      antilisterial effects of the treatment combinations, with little or no growth of
      the pathogen in 1-link or 5-link packages during 12 weeks of storage. In general,
      these treatments did not affect the sensory quality of frankfurters.

PMID- 15453577
TI  - Surface pasteurization of whole fresh cantaloupes inoculated with Salmonella
      poona or Escherichia coli.
AB  - Numerous outbreaks of salmonellosis by Salmonella Poona have been associated with
      the consumption of cantaloupe. Commercial washing processes for cantaloupe are
      limited in their ability to inactivate or remove this human pathogen. Our
      objective was to develop a commercial-scale surface pasteurization process to
      enhance the microbiological safety of cantaloupe. Populations of indigenous
      bacteria recovered from cantaloupes that were surface pasteurized at 96, 86, or
      76 degrees C for 2 to 3 min were significantly (P < 0.05) lower than those of the
      controls. Whole cantaloupes, surface inoculated with Salmonella Poona RM 2350 or
      Escherichia coli ATCC 25922 to a final cell concentration of ca. 5 log CFU/cm2
      were stored at 4 degrees C or room temperature (RT = 19+/-1 degrees C) for up to
      72 h before processing. Treatments at 76 degrees C for 2 to 3 min at 24 h
      postinoculation resulted in a reduction in excess of 5 log CFU/cm2 of Salmonella
      Poona and E. coli populations. Cantaloupes that were surface pasteurized and
      stored at 4 degrees C for 21 days retained their firmness qualities and had no
      visible mold growth compared with the controls, which became soft and moldy.
      These results indicate that surface pasteurization will enhance the
      microbiological safety of cantaloupes and will extend the shelf life of this
      commodity as well. Storage of untreated inoculated cantaloupes at RT for 24 to 72
      h postinoculation caused a significant (P < 0.05) increase in Salmonella Poona
      and E. coli populations compared with storage at 4 degrees C. This indicates that
      cantaloupes should be refrigerated as soon as possible following harvest to
      suppress the growth of any possible contaminant on the rind.

PMID- 15453578
TI  - Effect of thermoultrasonication on Salmonella enterica serovar Enteritidis in
      distilled water and intact shell eggs.
AB  - The combined effects of simultaneous application of ultrasonic waves and heat
      treatment (thermoultrasonication) on the survival of a strain of Salmonella
      enterica Enteritidis was studied in both distilled water and intentionally
      contaminated intact eggs immersed in water. Although minor differences were
      observed between parameters obtained for thermoultrasonic treatment of bacteria
      suspended in water and those attached to the shell egg, the thermoultrasonication
      effects were considered to be of the same level in the range of temperatures
      assayed (52 to 58 degrees C). This combined process presented a clearly higher
      killing effect than the heat treatment alone. It decreased the decimal reduction
      times (D-values) by 80 to 55%, respectively, in the range of temperatures for
      heat treatment when the organism was suspended in water, which means a 99.5%
      reduction (5D to >2D) of the original bacterial load versus a 90% reduction for
      the heat treatment alone. The practical implications of the phenomenon are
      discussed.

PMID- 15453579
TI  - A quantitative analysis of cross-contamination of Salmonella and Campylobacter
      spp. via domestic kitchen surfaces.
AB  - Epidemiological data indicate that cross-contamination during food preparation in
      the home contributes noticeably to the occurrence of foodborne diseases. To help
      prevent such occurrences, the inclusion of a cross-contamination model in
      exposure assessments would aid in the development and evaluation of interventions
      used to control the spread of pathogenic bacteria. A quantitative analysis was
      carried out to estimate the probability of contamination and the levels of
      Salmonella and Campylobacter spp. on salads as a result of cross-contamination
      from contaminated chicken carcasses via kitchen surfaces. Data on the prevalence
      and numbers of these bacteria on retail chicken carcasses and the use of unwashed
      surfaces to prepare foods were collected from scientific literature. The rates of
      bacterial transfer were collected from laboratory experiments and literature. A
      deterministic approach and Monte Carlo simulations that incorporated input
      parameter distributions were used to estimate the contamination of the product.
      The results have shown that the probability of Campylobacter spp. contamination
      on salads is higher than that of Salmonella spp., since both the prevalence and
      levels of Campylobacter spp. on chicken carcasses are higher than those of
      Salmonella spp. It is realistic to expect that a fraction of the human exposure
      to Campylobacter spp., in particular, originates from cross-contamination in
      private kitchens during food handling. The number of human campylobacteriosis
      cases could be reduced either by reducing the degree of Campylobacter spp.
      contamination on chicken carcasses or by improving the hygiene in private
      kitchens. To eliminate the cross-contamination route, it is important to use
      separate surfaces or to properly wash the surfaces during the preparation of raw
      and cooked foods or ready-to-eat foods.

PMID- 15453580
TI  - Load of polycyclic aromatic hydrocarbons in edible vegetable oils: importance of
      alkylated derivatives.
AB  - The presence of polycyclic aromatic hydrocarbons (PAHs) has been studied in
      different samples of olive oil, extra virgin olive oil, and refined seed oils. A
      high number of PAHs have been found, with a wide range of molecular weights and
      in concentrations that are high or even very high compared with the data obtained
      by other authors, especially in the seed oils. Among the PAHs identified, more
      than half are alkylated compounds, which account for the major part of the total
      PAH concentration in some of the samples. The total PAH concentrations in olive
      oils and extra virgin olive oils are similar, but the former present a higher
      proportion of heavy PAHs than the latter. The seed oils, in general, have much
      higher concentrations than the different types of olive oil and their PAH
      profiles are different. One of the olive oil samples exhibited a PAH distribution
      similar to that observed in olive pomace oil, suggesting possible adulteration.
      These data reveal that, in some cases, PAH profile provides useful information in
      relation to the possible origin of the contamination. We also observed large
      differences in PAH distribution between oils with the same label but from
      different batches. PAHs with varying degrees of carcinogenicity have been
      identified in all the samples, including benzo[a]pyrene, although this PAH was
      identified neither in the extra virgin olive oils nor in two of the seed oil
      samples.

PMID- 15453581
TI  - Angiotensin I-converting enzyme inhibitory activity of peptides derived from egg
      white proteins by enzymatic hydrolysis.
AB  - The hydrolysis of crude egg white with pepsin, trypsin, and chymotrypsin produced
      peptides with angiotensin-converting enzyme (ACE) inhibitory properties. These
      peptides were mainly derived from the proteolysis of ovalbumin. The most active
      hydrolysates were obtained after treatment with pepsin (50% inhibitory
      concentration [IC50], 55.3 microg/ml), with the fraction having a molecular mass
      lower than 3,000 Da giving the highest ACE inhibitory activity (IC50, 34.5
      microg/ml). Nine subfractions were collected from the fraction with a molecular
      mass lower than 3,000 Da using semipreparative reversed-phase high-performance
      liquid chromatography. Considerable ACE inhibitory activity (IC50 < 40 microg/ml)
      was found in three of them. These subfractions were analyzed by reversed-phase
      high-performance liquid chromatography-tandem mass spectrometry, and 14 peptides
      were identified. These sequences were synthesized, and their ACE inhibitory
      activities were measured. Among the identified peptides, two novel sequences with
      potent ACE inhibitory activity were found. The amino acid sequences of these
      inhibitors were identified as Arg-Ala-Asp-His-Pro-Phe-Leu and Tyr-Ala-Glu-Glu-Arg
      Tyr-Pro-Ile-Leu and showed IC50 values of 6.2 and 4.7 microM, respectively.

PMID- 15453582
TI  - Transfer of spinal cord material to subsequent bovine carcasses at splitting.
AB  - During the slaughter process, cattle carcasses are split by sawing centrally down
      the vertebral column, resulting in contamination of each half with spinal cord
      material. Using a novel method based on a real-time PCR assay, we measured saw
      mediated tissue transfer among carcasses. Up to 2.5% of the tissue recovered from
      each of the five subsequent carcasses by swabbing the split vertebral face came
      from the first carcass to be split; approximately 9 mg was spinal cord tissue.
      Under controlled conditions in an experimental abattoir, between 23 and 135 g of
      tissue accumulated in the saw after splitting five to eight carcasses. Of the
      total tissue recovered, between 10 and 15% originated from the first carcass, and
      between 7 and 61 mg was spinal cord tissue from the first carcass. At commercial
      plants in the United Kingdom, between 6 and 101 g of tissue was recovered from
      the saw, depending on the particular saw-washing procedure and number of
      carcasses processed. Therefore, if a carcass infected with bovine spongiform
      encephalopathy were to enter the slaughter line, the main risk of subsequent
      carcass contamination would come from the tissue debris that accumulates in the
      splitting saw. This work highlights the importance of effective saw cleaning and
      indicates that design modifications are required to minimize the accumulation of
      spinal cord tissue debris and, hence, the risk of cross-contamination of
      carcasses.

PMID- 15453583
TI  - Correlation of heavy metal concentrations with various factors in canned liver
      paste products using multivariate statistical strategies.
AB  - The content of Cu, Fe, Mn, Zn, Co, Cr, Ni, and Pb were determined in 496 samples
      of heat-treated canned liver pastes by atomic absorption spectrometry. Canned
      samples were classified according to the presence or absence of coated varnish on
      the inner side of the can. For each sample, two subsamples were taken: one from
      the area in contact with the side of the can, the other from the center of the
      container. Univariate (correlation, box and whisker) and multivariate (quality
      control charts, principal component analysis, and factor analysis) statistical
      techniques were applied to detect the presence of outliers and for exploratory
      data analysis. No significant differences (P < 0.05) were found between the
      subsamples considered, presence or absence of coated varnish, the sampling areas,
      or countries of origin. The multivariate analysis allows for the interpretation
      of grouping tendencies in samples. Cr, Ni, and Pb were associated with presence
      or absence of oxide in the can, and the essential metals (Fe, Cu, Zn, and Co)
      were associated with the kind of can. The samples tended to differentiate
      according to the type of container.

PMID- 15453584
TI  - Validated sandwich enzyme-linked immunosorbent assay for casein and its
      application to retail and milk-allergic complaint foods.
AB  - Cows' milk is a commonly allergenic food. Cross-contamination of milk proteins
      into nondairy, kosher-pareve foods prepared on shared processing equipment can
      cause severe, life-threatening reactions in milk-allergic individuals. A sandwich
      type enzyme-linked immunosorbent assay (ELISA; 96-well plate format) was
      developed for the detection of undeclared casein in foods. Rabbit anti-casein
      antibodies were used as the capture reagent. Food samples and standards were
      ground, extracted in 0.01 M phosphate-buffered saline, clarified by
      centrifugation, and added to the wells. Goat anti-casein antibodies were employed
      as the detector antibody, and the amount of antibody bound was determined with a
      commercial rabbit anti-goat immunoglobulin conjugated to alkaline phosphatase,
      with subsequent substrate reaction. Antibodies developed were specific to casein,
      with no cross-reaction observed with 30 foods and food ingredients. Non-milk
      containing products such as fruit juices, fruit juice bars, sorbets, and dark and
      pareve-labeled chocolate were purchased from June 2002 through June 2003. In
      addition, samples allegedly causing eight milk-allergic consumer complaints were
      analyzed. The ELISA had a detection limit of less than 0.5 ppm of casein. The
      casein content in the analyzed foods ranged from less than 0.5 ppm to more than
      40,000 ppm casein; undeclared casein residues were found in all of the samples
      implicated in allergic reactions. The levels of milk contamination in some of the
      other surveyed products could also be hazardous for milk-allergic consumers. This
      ELISA method provides a useful quality control tool for the food industry and
      could also be used as a validation of kosher-pareve status.

PMID- 15453585
TI  - Antioxidant activity of peptides derived from egg white proteins by enzymatic
      hydrolysis.
AB  - This work reports the antioxidant activity of peptides produced by enzymatic
      hydrolysis of crude egg white with pepsin. Four peptides included in the protein
      sequence of ovalbumin possessed radical scavenging activity higher than that of
      Trolox. The hydrolysate of egg white with pepsin for 3 h was previously found to
      exhibit a strong angiotensin I-converting enzyme (ACE) inhibitory activity in
      vitro. The combined antioxidant and ACE inhibition properties make it a very
      useful multifunctional preparation for the control of cardiovascular diseases,
      particularly hypertension. No correlation was found between antioxidant and ACE
      inhibitory activities. However, the peptide Tyr-Ala-Glu-Glu-Arg-Tyr-Pro-Ile-Leu,
      which was a strong ACE inhibitor (50% inhibitory concentration, 4.7 microM) also
      exhibited a high radical scavenging activity (oxygen radical absorbance capacity
      fluorescein value, 3.8 micromol of Trolox equivalent per micromol of peptide) and
      delayed the low-density lipoprotein lipid oxidation induced by Cu2+ at a
      concentration of approximately 0.16 mg/mg of low-density lipoprotein. Present
      results support that antioxidant peptides and amino acids not only act
      individually, but also cooperatively and synergistically.

PMID- 15453586
TI  - Experimental use of 2-nitropropanol for reduction of Salmonella Typhimurium in
      the ceca of broiler chicks.
AB  - The effect of 2-nitropropanol (2NPOH) administration on Salmonella enterica
      serovar Typhimurium in experimentally infected chicks was determined. Chicks
      orally challenged with 10(6) CFU/ml of a novobiocin- and naladixic acid-resistant
      Salmonella Typhimurium at 6 days of age were divided into three groups receiving
      0 (control), 6.5, and 13 mg 2NPOH per bird (experiment 1) or four groups
      receiving 0 (control), 13, 65, and 130 mg 2NPOH per bird (experiment 2).
      Treatments were administered orally 1 day post-Salmonella challenge. Cecal
      contents collected at necropsy 24 and 48 h after treatment were subjected to
      bacterial and volatile fatty acid (VFA) analysis. In experiment 1, concentrations
      (mean+/-SD log CFU per g) of Salmonella were reduced (P < 0.05) in the group
      administered 13 mg 2NPOH per bird at both the 24- and 48-h samplings compared
      with the controls (2.58+/-2.10 versus 4.64+/-1.79 and 2.88+/-2.78 versus 5.03+/
      2.42 at 24 and 48 h, respectively). In experiment 2, mean+/-SD populations of
      Salmonella were reduced (P < 0.05) in all groups receiving 2NPOH compared with
      untreated controls (3.65+/-2.01, 3.39+/-2.42, and 3.47+/-1.55 at 13, 65, and 130
      mg, respectively, versus 6.09+/-1.02). Propionate concentrations were reduced (P
      < 0.05) by the 13-mg 2NPOH per bird treatment. Total VFA concentrations from the
      group treated with 13 mg 2NPOH per bird were lower (P < 0.05) by 48, but not 24,
      hours posttreatment than those from the group treated with 6.5 mg 2NPOH per bird.
      These results demonstrate the inhibitory activity of 2NPOH against Salmonella
      Typhimurium in vivo.

PMID- 15453587
TI  - Antibiotic resistance and virulence traits of enterococci isolated from Baylough,
      an Irish artisanal cheese.
AB  - Eight representative Enterococcus strains from a collection of over 600
      previously isolated from an Irish artisanal cheese were subjected to phenotypic
      and genotypic analysis of antibiotic resistance and virulence properties. Genes
      encoding resistance to tetracycline (tet(M) and tet(L)) and/or erythromycin
      (erm(B)) were detected in five strains. In addition, all strains contained two or
      more of the virulence genes tested (agg, gel, cyl, esp, ace, efaAfs, and efaAfm).
      Further investigation into the transferability and environmental dissemination of
      these resistance and virulence traits will allow risk assessment and safety
      evaluation of artisanal cheeses.

PMID- 15453588
TI  - Antibacterial effect of water-soluble arrowroot (Puerariae radix) tea extracts on
      foodborne pathogens in ground beef and mushroom soup.
AB  - Antimicrobial activity of water-soluble arrowroot tea extract was evaluated
      against Escherichia coli O157:H7, Salmonella enterica Serotype Enteritidis,
      Listeria monocytogenes, and Staphylococcus aureus in ground beef and mushroom
      soup. The concentrations of arrowroot tea used were 0, 3, and 6% (wt/wt) for
      ground beef and 0, 1, 5, and 10% (wt/vol) for mushroom soup. Samples without tea
      extract were considered controls. Each sample was stored for 0, 1, 3, 5, and 7
      days at 7 degrees C for ground beef and for 0, 1, 3, and 5 days at 35 degrees C
      for mushroom soup. On each sampling time, proper dilutions were spread plated on
      each pathogen-specific agar. Viable cell counts of each pathogen were performed
      after incubation at 35 degrees C for 24 to 48 h. For ground beef, Salmonella
      Enteritidis and L. monocytogenes were slightly suppressed by approximately 1.5
      log, compared with the control, on day 7 at 3 and 6% arrowroot tea treatment. For
      mushroom soup, all test pathogens were suppressed by 6.5, 4.7, 3.4, and 4.3 log
      at 5% and 6.0, 4.7, 5.0, and 4.3 log at 10% against E. coli O157:H7, Salmonella
      Enteritidis, L. monocytogenes, and S. aureus, respectively, compared with the
      control on day 5. Mushroom soup with 1% arrowroot tea also showed 2.3- and 2.7
      log growth suppression of Salmonella Enteritidis and S. aureus, respectively,
      compared with the control on day 5. This study showed that the use of arrowroot
      tea would effectively inhibit the microbial growth of both gram-negative and gram
      positive foodborne pathogens in various foods, especially liquid foods.

PMID- 15453589
TI  - Kitchen practices used in handling broiler chickens and survival of Campylobacter
      spp. on cutting surfaces in Kampala, Uganda.
AB  - Cross-contamination during food preparation has been identified as an important
      factor associated with foodborne illnesses. Handling practices used during
      preparation of broiler chickens in 31 fast-food restaurants and 86 semisettled
      street stands (street vendors) were assessed by use of a standard checklist.
      These establishments used wood, plastic, or metal cutting surfaces during the
      preparation of broiler chickens. The survival of Campylobacter spp. on kitchen
      cutting surfaces was determined by inoculating approximately 10(6) CFU of
      Campylobacter jejuni onto sterile plastic, wooden, and metal cutting boards. The
      concentrations of the organisms were then assessed in triplicate on each type of
      cutting board over a 3-h period using standard microbiological methods for
      thermophilic Campylobacter spp. In 87% of food establishments, the same work area
      was used for preparation of raw and cooked chicken, and in 68% of these
      establishments the same cutting boards were used for raw and cooked chicken. None
      of the establishments applied disinfectants or sanitizers when washing contact
      surfaces. Campylobacter spp. survived on wooden and plastic but not on metal
      cutting boards after 3 h of exposure. The handling practices in food preparation
      areas, therefore, provide an opportunity for cross-contamination of Campylobacter
      spp. to ready-to-eat foods.

PMID- 15453590
TI  - A rapid method for determining the antimicrobial activity of novel natural
      molecules.
AB  - Preservatives used in the Agro-food industries may be of natural origin or
      obtained chemically. Because of the increasing interest of consumers in food
      products that contain only natural ingredients, studies on preservative molecules
      of natural origin, such as organic acids or peptides, have been reported in the
      past several years. Such studies, which require numerous assays, may be limited
      by the large amount of molecules required. Microscale assays provide an
      opportunity for testing natural components available in low quantity. This study
      examined a rapid method that used microplates for the evaluation of anti
      microbial substances. The method was validated using five foodborne pathogens. It
      required a low amount of product and was convenient for the determination of
      correlations between the bacterial growth inhibition and concentration of the
      antimicrobial substance.

PMID- 15453591
TI  - ComBase: a common database on microbial responses to food environments.
AB  - The advancement of predictive microbiology relies on available data that describe
      the behavior of microorganisms in different environmental matrices. For such
      information to be useful to the predictive microbiology research community, data
      must be organized in a manner that permits efficient access and data retrieval.
      Here, we describe a database protocol that encompasses observations of bacterial
      responses to food environments, resulting in a database (ComBase) for predictive
      microbiology purposes. The data included in ComBase were obtained from
      cooperating research institutes and from the literature and are publicly
      available via the Internet.

PMID- 15453592
TI  - Food consumption data in microbiological risk assessment.
AB  - The 1st International Conference on Microbiological Risk Assessment: Foodborne
      Hazards was held in July 2002. One of the goals of that conference was to
      evaluate the current status and future needs and directions of the science of
      microbial risk assessment. This article is based in part on a talk presented at
      that meeting. Here, we review the types of food consumption data available for
      use in microbial risk assessments and address their strengths and limitations.
      Consumption data available range from total population summary data derived from
      food production statistics to detailed information, derived from national food
      consumption surveys, about the types and amounts of food consumed at the
      individual level. Although population summary data are available for most
      countries, detailed data are available for a limited number of countries and may
      only be available in summary format. Despite the relatively large amount of
      detailed information collected by these national surveys, information crucial to
      microbial risk assessments, such as the specific types of foods, the eating
      patterns of susceptible populations, or an individual's propensity for consuming
      high-risk foods (e.g., eating undercooked hamburgers, raw shellfish, or
      temperature-abused foods), are not collected during these surveys.

PMID- 15453593
TI  - Effect of chemicals on the microbial evolution in foods.
AB  - In contrast with most chemical hazardous compounds, the concentration of food
      pathogens changes during processing, storage, and meal preparation, making it
      difficult to estimate the number of microorganisms or the concentration of their
      toxins at the moment of ingestion by the consumer. These changes are attributed
      to microbial proliferation, survival, and/or inactivation and must be considered
      when exposure to a microbial hazard is assessed. The number of microorganisms can
      also change as a result of physical removal, mixing of food ingredients,
      partitioning of a food product, or cross-contamination (M. J. Nauta. 2002. Int.
      J. Food Microbiol. 73:297-304). Predictive microbiology, i.e., relating these
      microbial evolutionary patterns to environmental conditions, can therefore be
      considered a useful tool for microbial risk assessment, especially in the
      exposure assessment step. During the early development of the field (late 1980s
      and early 1990s), almost all research was focused on the modeling of microbial
      growth over time and the influence of temperature on this growth. Later, modeling
      of the influence of other intrinsic and extrinsic parameters garnered attention.
      Recently, more attention has been given to modeling of the effects of chemicals
      on microbial inactivation and survival. This article is an overview of different
      applied strategies for modeling the effect of chemical compounds on microbial
      populations. Various approaches for modeling chemical growth inhibition, the
      growth-no growth interface, and microbial inactivation by chemicals are reviewed.

PMID- 15453594
TI  - Draft risk assessment of the public health impact of Escherichia coli O157:H7 in
      ground beef.
AB  - An assessment of the risk of illness associated with Escherichia coli O157:H7 in
      ground beef was drafted in 2001. The exposure assessment considers farm,
      slaughter, and preparation factors that influence the likelihood of humans
      consuming ground beef servings containing E. coli O157:H7 and the number of cells
      in a contaminated serving. Apparent seasonal differences in prevalence of cattle
      infected with E. coli O157:H7 corresponded to seasonal differences in human
      exposure. The model predicts that on average 0.018% of servings consumed during
      June through September and 0.007% of servings consumed during the remainder of
      the year are contaminated with one or more E. coli O157:H7 cells. This exposure
      risk is combined with the probability of illness given exposure (i.e., dose
      response) to estimate a U.S. population risk of illness of nearly one illness in
      each 1 million (9.6 x 10(-7)) servings of ground beef consumed. Uncertainty about
      this risk ranges from about 0.33 illness in every 1 million ground beef servings
      at the 5th percentile to about two illnesses in every 1 million ground beef
      servings at the 95th percentile.

PMID- 15453595
TI  - An epidemiologic critique of current microbial risk assessment practices: the
      importance of prevalence and test accuracy data.
AB  - Data deficiencies are impeding the development and validation of microbial risk
      assessment models. One such deficiency is the failure to adjust test-based
      (apparent) prevalence estimates to true prevalence estimates by correcting for
      the imperfect accuracy of tests that are used. Such adjustments will facilitate
      comparability of data from different populations and from the same population
      over time as tests change and the unbiased quantification of effects of
      mitigation strategies. True prevalence can be estimated from apparent prevalence
      using frequentist and Bayesian methods, but the latter are more flexible and can
      incorporate uncertainty in test accuracy and prior prevalence data. Both
      approaches can be used for single or multiple populations, but the Bayesian
      approach can better deal with clustered data, inferences for rare events, and
      uncertainty in multiple variables. Examples of prevalence inferences based on
      results of Salmonella culture are presented. The opportunity to adjust test-based
      prevalence estimates is predicated on the availability of sensitivity and
      specificity estimates. These estimates can be obtained from studies using
      archived gold standard (reference) samples, by screening with the new test and
      follow-up of test-positive and test-negative samples with a gold standard test,
      and by use of latent class methods, which make no assumptions about the true
      status of each sampling unit. Latent class analysis can be done with maximum
      likelihood and Bayesian methods, and an example of their use in the evaluation of
      tests for Toxoplasma gondii in pigs is presented. Guidelines are proposed for
      more transparent incorporation of test data into microbial risk assessments.

PMID- 15453596
TI  - Intraspecies variability in the dose-response relationship for Salmonella
      Enteritidis associated with genetic differences in cellular immune response.
AB  - To evaluate the effects of differences in host cellular immunity, we studied the
      dose-response relationship for infection with Salmonella enterica serovar
      Enteritidis (SE) in two different rat strains, skewed towards T helper 1 (Th1,
      Lewis rats) or T helper 2 (Th2, Brown Norway rats) immunoregulation. Rats were
      exposed orally to different doses of SE after overnight starvation and
      neutralization of gastric acid. Animals were observed for clinical signs of
      disease, fecal excretion and SE load in spleen and cecum, histopathology of the
      cecum, hematology, and cellular and humoral immune responses. Exponential dose
      response models were used for binary or continuous outcomes to analyze the
      experimental data. Cytokine patterns, antibody isotypes, and contact
      hypersensitivity tests confirmed that Lewis rats are Th1 prone, whereas Brown
      Norway rats are Th2 prone. The probability of infection per single SE cell was
      approximately 100 times higher in Brown Norway rats than in Lewis rats. Cellular
      immune responses were more pronounced in Lewis rats but antibody responses were
      higher in Brown Norway rats. When infected, colonization levels and inflammation
      are highest in the intestinal tract of Th2 skewed rats, but systemic infection is
      more intense in Th1 skewed rats. Successful colonization by only one or two SE
      clones resulted in a marked increase of neutrophil counts by a factor of two to
      three in both rat strains.

PMID- 15453597
TI  - Microbiological risk assessment in developing countries.
AB  - Microbiological risk assessment (MRA) has been evolving at the national and
      international levels as a systematic and objective approach for evaluating
      information pertaining to microbiological hazards in foods and the risks they
      pose. This process has been catalyzed by international food trade requirements to
      base sanitary measures on sound scientific evidence and appropriate risk
      assessments. All countries, including developing countries, need to understand
      and use MRA. MRA is resource intensive, as has been demonstrated by some of the
      the assessments undertaken in industrialized countries. However, when used in the
      appropriate circumstances MRA offers many benefits. The process of undertaking
      MRA improves the understanding of key issues, enables an objective evaluation of
      risk management options, and provides a scientific justification for actions.
      Although the gap between developing countries and some industrialized countries
      is quite extensive with regard to MRA, many developing countries recognize the
      need to at least understand and move toward using MRA. This process requires
      development of infrastructure and enhancement of scientific and technical
      expertise while making optimal use of limited resources. International
      organizations, such as the Food and Agriculture Organization of the United
      Nations, are in a position to provide countries with guidance, training,
      information resources, and technical assistance to develop and/or strengthen food
      safety infrastructure. Enhanced cooperation and collaboration at all levels are
      needed for such efforts to be successful and to ensure that MRA, as a food safety
      tool, is available to all countries.

PMID- 15453598
TI  - Archiving of food samples from restaurants and caterers--quantitative profiling
      of outbreaks of foodborne salmonellosis in Japan.
AB  - The Ministry of Health, Labor and Welfare (former MHW) of Japan issued a
      Directive in 1997 advising restaurants and caterers to freeze portions of both
      raw food and cooked dishes for at least 2 weeks. This system has been useful for
      determining vehicle foods at outbreaks. Enumeration of bacteria in samples of
      stored food provide data about pathogen concentrations in the implicated food.
      Data on Salmonella concentrations in vehicle foods associated with salmonellosis
      outbreaks were collected in Japan between 1989 and 1998. The 39 outbreaks that
      occurred during this period were categorized by the settings where the outbreaks
      took place, and epidemiological data from each outbreak were summarized.
      Characteristics of outbreak groups were analyzed and compared. The effect of new
      food-storage system on determination of bacterial concentration was evaluated.
      Freezing and nonfreezing conditions prior to microbial examination were compared
      in the dose-response relationship. Data from outbreaks in which implicated foods
      had been kept frozen suggested apparent correlation between the Salmonella dose
      ingested and the disease rate. Combined with results of epidemiological
      investigation, quantitative data from the ingested pathogen could provide
      complete dose-response data sets.

PMID- 15453599
TI  - Application of elements of microbiological risk assessment in the food industry
      via a tiered approach.
AB  - Food safety control is a matter for concern for all parts of the food supply
      chain, including governments that develop food safety policy, food industries
      that must control potential hazards, and consumers who need to keep to the
      intended use of the food. In the future, food safety policy may be set using the
      framework of risk analysis, part of which is the development of (inter)national
      microbiological risk assessment (MRA) studies. MRA studies increase our
      understanding of the impact of risk management interventions and of the
      relationships among subsequent parts of food supply chains with regard to the
      safety of the food when it reaches the consumer. Application of aspects of MRA in
      the development of new food concepts has potential benefits for the food
      industry. A tiered approach to applying MRA can best realize these benefits. The
      tiered MRA approach involves calculation of microbial fate for a product and
      process design on the basis of experimental data (e.g., monitoring data on
      prevalence) and predictive microbiological models. Calculations on new product
      formulations and novel processing technologies provide improved understanding of
      microbial fate beyond currently known boundaries, which enables identification of
      new opportunities in process design. The outcome of the tiered approach focuses
      on developing benchmarks of potential consumer exposure to hazards associated
      with new products by comparison with exposure associated with products that are
      already on the market and have a safe history of use. The tiered prototype is a
      tool to be used by experienced microbiologists as a basis for advice to product
      developers and can help to make safety assurance for new food concepts
      transparent to food inspection services.

PMID- 15453600
TI  - Concepts and tools for predictive modeling of microbial dynamics.
AB  - Description of microbial cell (population) behavior as influenced by dynamically
      changing environmental conditions intrinsically needs dynamic mathematical
      models. In the past, major effort has been put into the modeling of microbial
      growth and inactivation within a constant environment (static models). In the
      early 1990s, differential equation models (dynamic models) were introduced in the
      field of predictive microbiology. Here, we present a general dynamic model
      building concept describing microbial evolution under dynamic conditions.
      Starting from an elementary model building block, the model structure can be
      gradually complexified to incorporate increasing numbers of influencing factors.
      Based on two case studies, the fundamentals of both macroscopic (population) and
      microscopic (individual) modeling approaches are revisited. These illustrations
      deal with the modeling of (i) microbial lag under variable temperature conditions
      and (ii) interspecies microbial interactions mediated by lactic acid production
      (product inhibition). Current and future research trends should address the need
      for (i) more specific measurements at the cell and/or population level, (ii)
      measurements under dynamic conditions, and (iii) more comprehensive
      (mechanistically inspired) model structures. In the context of quantitative
      microbial risk assessment, complexity of the mathematical model must be kept
      under control. An important challenge for the future is determination of a
      satisfactory trade-off between predictive power and manageability of predictive
      microbiology models.

PMID- 15453601
TI  - Risk assessment prediction from genome sequences: promises and dreams.
AB  - The application of bacterial genomics opens new avenues of research on foodborne
      pathogens. Foodborne pathogens must be able to colonize their hosts and survive
      transmission from host to host. Different groups of genes are involved in the
      processes of survival, colonization, and virulence, and such genes are potential
      targets for risk assessment and intervention strategies. Filtering from genome
      sequences the genes relevant to these processes is a major challenge, and
      although many tools are already available for analyses, this type of data mining
      is just beginning. For the simplest application, gene comparison, it is important
      to know how gene function, for instance in virulence, is being defined and
      tested. In other genomic applications, reserachers look for specific properties
      or characteristics of (virulence) genes to identify novel gene candidates. Each
      approach has pitfalls, and gene candidates must be tested in the lab to confirm
      their function. Models for colonization and virulence are available for most
      although not all pathogens. Models for survival and stress responses are needed
      to increase the utilization of genomic approaches to risk assessment. Here, I
      discuss how genome sequences are likely to help in microbial risk assessment of
      foodborne pathogens and how dreams may become promises.

PMID- 15453602
TI  - Initiating and managing risk assessments within a risk analysis framework:
      FDA/CFSAN'S practical approach.
AB  - Management of risk analysis involves the integration and coordination of
      activities associated with risk assessment, risk management, and risk
      communication. Risk analysis is used to guide regulatory decision making,
      including trade decisions at national and international levels. The U.S. Food and
      Drug Administration Center for Food Safety and Applied Nutrition (CFSAN) formed a
      working group to evaluate and improve the quality and consistency of major risk
      assessments conducted by the Center. Drawing on risk analysis experiences, CFSAN
      developed a practical framework for initiating and managing risk assessments,
      including addressing issues related to (i) commissioning a risk assessment, (ii)
      interactions between risk managers and risk assessors, and (iii) peer review.

PMID- 15453603
TI  - Antimicrobial resistance risk assessment in food safety.
AB  - Microbiological risk assessments generally focus on estimating adverse human
      health risks from exposures to human pathogenic microbes. The assessment of
      potential human health risks posed by pathogens that have acquired resistance to
      antimicrobial drugs is a new application of risk assessment that is closely
      related to microbiological risk assessment. Antimicrobial resistance risk
      assessment is a risk analyticalprocess that focuses on resistance determinants as
      hazardous agents that might lead to drug-resistant microbial infections in humans
      exposed to bacteria carrying the determinants. Antimicrobial-resistant infections
      could occur directly from actively inavading or opportunistic pathogens or
      indirectly from the transfer of resistance genes to other bacteria. Here, we
      discuss risk assessment models that might be employed to estimate risks from drug
      resistant bacteria in the animal food pathway and the types of models and data
      that may be used for microbiological risk assessments or antimicrobial resistance
      risk assessments.

PMID- 15453604
TI  - 1st International Conference on Microbiological Risk Assessment: foodborne
      hazards--what we heard.

PMID- 15453606
TI  - The healing touch.

PMID- 15453605
TI  - Government funding & hospital planning: partners in preparedness.

PMID- 15453607
TI  - Health care's most wired. A wired exchange.
AB  - There was a time when innovation in health care information technology meant
      being at the cutting edge of managerial systems. Hospitals made significant
      investments in financially oriented technology. In the past five years, the
      investment in clinical IT appears to have outstripped the investment in
      managerial systems, including enterprise resource planning aimed at improving the
      supply chain.

PMID- 15453608
TI  - The borrowers: tracking loaner instruments and implants.

PMID- 15453609
TI  - Can we talk? Hospitals combine technologies to increase communication.

PMID- 15453610
TI  - Stats. Standard practice.

PMID- 15453611
TI  - Impairment of spermatogenesis leading to infertility.
AB  - Highly differentiated spermatozoa are generated through multiple cellular and
      molecular processes maintained by Sertoli cells. The cellular events associated
      with germ cells include proliferation, protein folding and transportation, as
      well as sequential changes in chromatin and cell organelles. These processes are
      strictly controlled by the expression of specific genes, including transcription
      and DNA replication/repair. This complex spermatogenesis is impaired by a
      mutation such as gene knockout, which leads to a variety of morphological and
      functional abnormalities found in mature spermatozoa. An overview of
      spermatogenesis impairment induced by gene knockout is provided in the present
      review.

PMID- 15453612
TI  - Periodic pattern formation in reaction-diffusion systems: an introduction for
      numerical simulation.
AB  - The aim of the present review is to provide a comprehensive explanation of Turing
      reaction-diffusion systems in sufficient detail to allow readers to perform
      numerical calculations themselves. The reaction-diffusion model is widely studied
      in the field of mathematical biology, serves as a powerful paradigm model for
      self-organization and is beginning to be applied to actual experimental systems
      in developmental biology. Despite the increase in current interest, the model is
      not well understood among experimental biologists, partly because appropriate
      introductory texts are lacking. In the present review, we provide a detailed
      description of the definition of the Turing reaction-diffusion model that is
      comprehensible without a special mathematical background, then illustrate a
      method for reproducing numerical calculations with Microsoft Excel. We then show
      some examples of the patterns generated by the model. Finally, we discuss future
      prospects for the interdisciplinary field of research involving mathematical
      approaches in developmental biology.

PMID- 15453613
TI  - GABAergic signaling in the developing cerebellum.
AB  - In the adult central nervous system (CNS), GABA is a predominant inhibitory
      neurotransmitter that regulates glutamatergic activity. Recent studies have
      revealed that GABA serves as an excitatory transmitter in the immature CNS and
      acts as a trophic factor for brain development. Furthermore, synaptic
      transmission by GABA is also involved in the expression of higher brain
      functions, such as memory, learning and anxiety. These results indicate that GABA
      plays various roles in the expression of brain functions and GABAergic roles
      change developmentally in accordance with alterations in GABAergic transmission
      and signaling. We have investigated morphologically the developmental changes in
      the GABAergic transmission system and the key factors important for the formation
      of GABAergic synapses and networks using the mouse cerebellum, which provides an
      ideal system for the investigation of brain development. Here, we focus on GABA
      and GABA(A) receptors in the developing cerebellum and address the processes of
      how GABA exerts its effect on developing neurons and the mechanisms underlying
      the formation of functional GABAergic synapses.

PMID- 15453614
TI  - Serine proteases regulating synaptic plasticity.
AB  - A number of molecules have been postulated to be involved in long-term
      potentiation, an experimental model for learning and short-term memory. Although
      the molecular mechanisms of the long-term potentiation have been considerably
      well understood, it is not yet known why and how real memory can last very long
      with outstanding stability. A mechanical change of synaptic morphology at
      acquisition, consolidation and retention of memory is hypothesized to explain
      long-lasting memory. Changes in the synaptic morphology may be due, at least in
      part, to local extracellular proteolysis of cell adhesion and extracellular
      matrix molecules. Some extracellular serine proteases of the Clan PA family may
      modulate synaptic adhesion and associate with long-term potentiation and learning
      behavior. In the present review, candidate proteases that are involved in the
      hippocampal memory are overviewed.

PMID- 15453615
TI  - Immunocytochemistry of keratan sulfate proteoglycan and dermatan sulfate
      proteoglycan in porcine tooth-germ dentin.
AB  - Keratan sulfate proteoglycan and dermatan sulfate proteoglycan have been reported
      to inhibit collagen fibrillogenesis. We investigated their distribution in order
      to evaluate the role of proteoglycan in dentinogenesis. Specimens of porcine
      tooth-germ dentin and erupted teeth were the materials on which antibodies to
      keratin sulfate and dermatan sulfate proteoglycan were used. Predentin was found
      to be positive for both antibodies and the reaction ceased in the calcification
      front. Uniformly thick collagen fibrils (30-70 nm in diameter) were distributed
      in the predentin matrix, which would become intertubular dentin in the future.
      Both antibodies reacted positively along these fibrils. In contrast, along the
      surface layer of dentin in the tooth germ and that in erupted teeth, collagen
      fibrils of 10-300 nm in diameter were noted occasionally in dentinal tubules
      whose odontoblastic processes had disappeared and these heterogeneous fibrils
      were negative for both antibodies. Our findings suggest that keratan sulfate
      proteoglycan and dermatan sulfate proteoglycan distributed in the predentin
      inhibit calcification of collagen fibrils in the uncalcified matrix and disappear
      in the calcification front. It is further suggested that keratan sulfate
      proteoglycan and dermatan sulfate proteoglycan distributed along collagen fibrils
      in the predentin matrix maintain uniform thickness, whereas collagen fibrils in
      dentinal tubules varied in thickness because of the absence of involvement of
      both proteoglycans. Therefore, keratan sulfate proteoglycan and dermatan sulfate
      proteoglycan were thought to be involved in both calcification and matrix
      formation.

PMID- 15453616
TI  - Reduction of formaldehyde concentrations in the air and cadaveric tissues by
      ammonium carbonate.
AB  - The reduction of formaldehyde by ammonium carbonate was examined in cadavers and
      in vitro. Formaldehyde concentrations in the air (10 cm above human cadavers) and
      in various cadaveric tissues were measured with or without perfusion of ammonium
      carbonate solution into formaldehyde-fixed cadavers. Air samples were monitored
      using Kitagawa gas detector tubes. For measurement of formaldehyde in tissues,
      muscles and organs were cut into small pieces and tissue fluids were separated
      out by centrifugation. These specimen fluids were diluted, supplemented with 3
      methyl-2-benzothiazolinone hydrazone hydrochloride and quantified by
      spectrophotometry. In five cadavers without ammonium carbonate treatment, the
      formaldehyde concentrations in the air above the thorax and in various tissue
      fluids were 1.2-3.0 p.p.m. and 0.15-0.53%, respectively. Arterial reperfusion of
      saturated ammonium carbonate solution (1.0, 1.5 or 2.0 L) into five formaldehyde
      fixed cadavers successfully reduced the formaldehyde levels, both in the air (0.5
      1.0 p.p.m.) and in various tissue fluids (0.012-0.36%). In vitro experiments
      demonstrated that formaldehyde concentrations decreased, first rapidly and then
      gradually, with the addition of ammonium carbonate solution into fluids
      containing formaldehyde. It was confirmed that formaldehyde reacted with the
      ammonium carbonate and was thereby changed into harmless hexamethylenetetramine.
      The application of ammonium carbonate solution via intravascular perfusion and,
      if necessary, by infusion into the thoracic and peritoneal cavities, injection
      into muscles and spraying on denuded tissues can be anticipated to reduce
      formaldehyde to satisfactorily low levels in cadaveric tissues and, consequently,
      in the air, which may provide safe and odorless dissecting rooms.

PMID- 15453617
TI  - Arterial supply and biliary drainage of the dorsal liver: a dissection study
      using controlled specimens.
AB  - Liver surgeons favor using the entity called the 'dorsal liver' (i.e. the caudate
      lobe and other paracavally located liver parenchyme of segments 7 and 8).
      According to minute dissection of 48 livers, we describe the territories of the
      left/right portal veins, hepatic ducts and hepatic arteries in the dorsal liver.
      In the caudate lobe, the right hepatic artery, rather than the left hepatic
      artery (23/48 vs 19/48 for right vs left, respectively), tended to supply the
      'left' portal vein territory. Similarly, paradoxical drainage patterns, such as
      the right hepatic duct draining the left portal vein territory, were found in
      seven of 48 livers. In the territory of the hilar bifurcation, right hepatic
      artery dominance was also evident and various bile drainage patterns were found.
      These included double drainage by the bilateral hepatic ducts (3/48) and drainage
      into the confluence of bilateral ducts (6/48). In contrast, the arterial supply
      and biliary drainage of the paracavally located parenchyme of segments 7 and 8
      usually depended on the proper segmental arteries and ducts and their variations
      were within the range of those found in other parts of the right lobe. Therefore,
      the dorsal liver concept may not be anatomical but, rather, simply aimed at
      usefulness in surgery. Nevertheless, clear subdivision of the caudate lobe
      according to biliary drainage and/or arterial supply seemed difficult because of
      the paradoxical relatioships among the portal vein, hepatic artery and bile duct.
      Consequently, the present results support extended surgery based on the dorsal
      liver concept for carcinomas involving the caudate lobe.

PMID- 15453618
TI  - On unknown bone bridge and foramen of the atlas.
AB  - The atlas of a 52-year-old male Japanese cadaver, which had been removed and
      macerated, presented a bilateral unknown bone bridge forming a foramen (Case 1).
      The bone bridge connected the ponticulus lateralis (PL) and posterior (PP) to
      form an oval foramen between the superior roots of both ponticuli. The atlas of a
      69-year-old male Japanese cadaver was found to have similar variations in situ
      (Case 2). In this case, the right bone bridge connected the superior root of the
      incomplete PL and the inferior root of the also incomplete PP to form a long
      ellipsoid foramen opening medially. The medial opening of the foramen was closed
      by a ligamentous connective tissue in situ. The condylar emissary vein passed
      this complete foramen to join the cervical epidural venous plexus. The similar
      bilateral foramen in case 1 was supposed to pass the same vein as in case 2. The
      bone bridge between the two ponticuli and the resulting foramen mentioned above
      have not been described previously, as far as we know. We propose that these
      structures be called the ponticulus interponticularis atlantis and the foramen
      atlantoideum interponticulare, respectively.

PMID- 15453619
TI  - International Association for Hospice and Palliative Care (IAHPC): working to
      improve access to palliative care.

PMID- 15453620
TI  - Methods for assessment of cognitive failure and delirium in palliative care
      patients: implications for practice and research.
AB  - The most commonly encountered clinical conditions presenting with cognitive
      failure (CF) are delirium, dementia and amnestic disorders. Of these, delirium is
      probably the most prevalent in palliative care, and it is potentially reversible.
      Thus, improvement in diagnostics seems warranted. The objectives of this review
      were to examine the methods for assessment of CF and delirium in palliative care.
      Twenty-two studies were reviewed: 64% were published in 2000 or later. Twelve
      reports focused on delirium, six on CF, while the remaining four assessed
      confusion (2), hallucinations and general psychological morbidity. Median sample
      size was 100 (20393). Ten different instruments were used: The Mini Mental State
      Exam was used in 13 studies. Five studies were validation reports of new or
      existing instruments. The term CF is an imprecise description of a loss in one or
      more of the cognitive functions. The interchangeable use of CF as a description
      of specific diagnoses should be avoided, as this contributes to prevalence rates
      that are not representative. Assessment tools that discriminate between the
      different diagnostic entities presenting with CF should be used in future
      studies.

PMID- 15453621
TI  - Evolving spinal analgesia practice in palliative care.
AB  - Intraspinal analgesia can be helpful in some patients with intractable pain. Over
      15 years palliative care professionals evolved their spinals policy through a
      repeated series of evaluations, discussions and literature reviews. One hundred
      intraspinal lines were then reviewed. Notable changes in policy were the switch
      from epidurals to intrathecals, and the insertion of lines during working hours
      rather than as emergencies. Our efficacy, and frequency of adverse effects, is
      equal or better to published studies. Key issues in reducing adverse effects were
      the improved care of the spinal line exit site, a change from bolus
      administration to continuous infusions, and modifying line insertion techniques.
      Current policy is to use continuous infusions of diamorphine and bupivacaine in a
      1:5 ratio through externalized intrathecal lines. The lines are effective in
      approximately two thirds of patients and can be kept in place for up to 18
      months. The policy continues to be updated and common documentation is now in
      place.

PMID- 15453622
TI  - A retrospective review of the use of alfentanil in a hospital palliative care
      setting.
AB  - Alfentanil is becoming an alternative to diamorphine when parental opioids are
      required, especially in the presence of renal insufficiency. Its pharmacokinetic
      properties suggest that tolerance may be rapidly induced, whilst concomitant
      administration of drugs that interfere with the cytochrome P450 system may alter
      its metabolism. This retrospective audit looked at the use of subcutaneous
      alfentanil in a palliative care setting over a 21-month period. Forty-eight out
      of the 81 notes identified were available for analysis. Alfentanil was used for a
      median of 9 days (range 1-81) with median increase in dose of 80% (range 0
      1125%). No significant correlation was found between duration of infusion and
      dose escalation. In addition no significant correlation was found between dose
      escalation and concomitant drugs that either inhibited or induced the P450
      system. This is the first study to investigate the use of relatively long-term
      use of parenteral alfentanil. The results suggest that neither tolerance nor
      concomitant drug administration is of clinical significance in the dose
      escalation.

PMID- 15453623
TI  - Topical benzydamine cream and the relief of pressure pain.
AB  - OBJECTIVE: To determine whether topical benzydamine hydrochloride 3% cream is
      more effective than placebo in reducing pain related to pressure areas in
      palliative care patients. DESIGN: Randomized double-blind, placebo-controlled
      trial. SETTING: Three specialist palliative care units in the north of England,
      with local ethical committee approval for all sites. SUBJECTS: Hospice in
      patients with pain related to pressure areas. INTERVENTIONS: A single application
      of either benzydamine hydrochloride 3% cream or placebo cream to the painful
      pressure area. MAIN OUTCOME MEASURES: Pain assessed using 100 mm VAS, an 11-point
      numerical pain score and a five-point pain relief score. RESULTS: There was no
      statistically significant difference between topical benzydamine hydrochloride 3%
      cream and placebo cream in reducing pain related to pressure areas in palliative
      care patients. CONCLUSIONS: This study does not demonstrate a statistically
      significant difference between the two treatments. However the study does provide
      reliable information with respect to the use of different pain measurement tools
      in late-stage palliative patients. It also provides information regarding the
      baseline characteristics of this group of patients which may be useful in the
      planning of any future similar studies.

PMID- 15453624
TI  - Systematic review of the problems and issues of accessing specialist palliative
      care by patients, carers and health and social care professionals.
AB  - OBJECTIVES: To determine the problems and issues of accessing specialist
      palliative care by patients, informal carers and health and social care
      professionals involved in their care in primary and secondary care settings. DATA
      SOURCES: Eleven electronic databases (medical, health-related and social science)
      were searched from the beginning of 1997 to October 2003. Palliative Medicine
      (January 1997-October 2003) was also hand-searched. STUDY SELECTION: Systematic
      search for studies, reports and policy papers written in English. DATA
      EXTRACTION: Included papers were data-extracted and the quality of each included
      study was assessed using 10 questions on a 40-point scale. RESULTS: The search
      resulted in 9921 hits. Two hundred and seven papers were directly concerned with
      symptoms or issues of access, referral or barriers and obstacles to receiving
      palliative care. Only 40 (19%) papers met the inclusion criteria. Several
      barriers to access and referral to palliative care were identified including lack
      of knowledge and education amongst health and social care professionals, and a
      lack of standardized referral criteria. Some groups of people failed to receive
      timely referrals e.g., those from minority ethnic communities, older people and
      patients with nonmalignant conditions as well as people that are socially
      excluded e.g., homeless people. CONCLUSIONS: There is a need to improve education
      and knowledge about specialist palliative care and hospice care amongst health
      and social care professionals, patients and carers. Standardized referral
      criteria need to be developed. Further work is also needed to assess the needs of
      those not currently accessing palliative care services.

PMID- 15453625
TI  - Equity of access to adult hospice inpatient care within north-west England.
AB  - There is a growing debate about the question of equity of access to hospice and
      palliative care services. Even countries with relatively well developed
      palliative care systems are considered to have problems of access and inequity of
      provision. Despite these concerns, we still lack a relevant evidence base to
      serve as a guide to action. We present an analysis of access to adult hospice
      inpatient provision in the north-west region of England that employs Geographical
      Information Systems (GIS). Measures of the possible demand for, and supply of,
      hospice inpatient services are used to determine the potential accessibility of
      cancer patients, assessed at the level of small areas (electoral wards). Further,
      the use of deprivation scores permits an analysis of the equity of access to
      adult inpatient hospice care, leading to the identification of areas where
      additional service provision may be warranted. Our research is subject to a
      number of caveats--it is limited to inpatient hospice provision and does not
      include other kinds of inpatient and community-based palliative care services.
      Likewise, we recognise that not everyone with cancer will require palliative care
      and also that palliative care needs exist among those with nonmalignant
      conditions. Nevertheless, our methodology is one that can also be applied more
      generally.

PMID- 15453626
TI  - Emotional burden of nurses in palliative sedation therapy.
AB  - BACKGROUND: Palliative sedation therapy is often required in terminally ill
      cancer patients, and may cause emotional burden for nurses. The primary aims of
      this study were 1) to clarify the levels of nurses' emotional burden related to
      sedation, and 2) to identify the factors contributing to the burden levels.
      METHODS: A questionnaire survey of 3187 nurses, with a response rate of 82%.
      RESULTS: Eighty-two percent of the nurses (n = 2607) had clinical experience in
      continuous-deep sedation. Thirty per cent reported that they wanted to leave
      their current work situation due to sedation-related burden (answering
      occasionally, often, or always). Also, 12% of the nurses stated that being
      involved in sedation was a burden, 12% that they felt helpless when patients
      received sedation, 11% that they would avoid a situation in which they had to
      perform sedation if possible, and 4% that they felt what they had done was of no
      value when they performed sedation. The higher nurse-perceived burden was
      significantly associated with shorter clinical experience, nurse-perceived
      insufficient time in caring for patients, lack of common understanding of
      sedation between physicians and nurses, team conference unavailability, frequent
      experience of conflicting wishes for sedation between patient and family, nurse
      perceived inadequate interpersonal skills, belief that it was difficult to
      diagnose refractory symptoms, belief that sedation would hasten death, belief
      that sedation was ethically indistinguishable from euthanasia, nurse-perceived
      inadequate coping with their own grief, and nurses' personal values contradictory
      to sedation therapy. CONCLUSIONS: A significant number of nurses felt serious
      emotional burden related to sedation. To relieve nurses' emotional burden, we
      encourage 1) management efforts to reduce work overload, 2) a team approach to
      resolving conflicting opinions, especially between physicians and nurses, 3) co
      ordination of early patient-family meetings to clarify their preferred end-of
      life care, 4) education and training about sedation specifically focused on
      interpersonal skills, systematic approaches to diagnosing refractory symptoms,
      minimum life-threatening potency in sedation, and ethical principals
      differentiating sedation from euthanasia, and 5) exploring nurses' personal
      values through the patient-centered principle.

PMID- 15453627
TI  - A prospective study to determine the association between physical symptoms and
      depression in patients with advanced cancer.
AB  - Depression is a common symptom in patients with advanced cancer and patients who
      are depressed may also have physical symptoms which are difficult to palliate and
      which improve as their depression is appropriately treated. This study was
      carried out to determine if there was an association between depression and
      physical symptoms in patients with advanced cancer and to establish whether a
      seven-item verbal rating scale asking patients to verbally rate the severity of
      physical symptoms together with low mood could be used to screen for depression.
      The scale was validated against a semi-structured clinical interview according to
      DSM IV criteria. Seventy-four patients participated with an age range of 28-92
      years. All patients had an ECOG performance status of two or three. The
      prevalence of major depression in this study was found to be 27% (95% C.I. 17
      37%). The mean score on the verbal rating scale was 28.77 (median score 29.5)
      (95% C.I., 26.23 - 31.31; range 0-65). A cut-off of > or = 30 gave a sensitivity
      of 65% and specificity of 59%, with positive and negative predictive values of
      37% and 82% respectively. The verbal mood item alone had an optimal cut-off point
      of 3, with a sensitivity of 80% and specificity of 43%. Patients diagnosed as
      being depressed according to psychiatric interview rated each symptom higher than
      nondepressed patients. The verbal mood item and total verbal rating score
      correlated with a high significance (rs = 0.607, P < 0.01), implying a
      relationship between a patient's subjective mood state and other symptoms. Both
      using the verbal scale and asking patients to verbally rate their mood alone had
      poor efficacy as a screening tool. However, there is a close association between
      physical symptoms and the presence of depression in palliative care patients.

PMID- 15453628
TI  - Thoughts of patients with advanced heart failure on dying.
AB  - OBJECTIVE: To explore, over a one-year period, the ideas and attitudes of
      patients with end-stage cardiac failure concerning dying. DESIGN: Prospective
      longitudinal multiple case study using qualitative interview techniques.
      PARTICIPANTS: Thirty-one patients from two hospitals who fulfilled one or more of
      the following criteria: NYHA III or IV, ejection fraction < 25%, at least one
      hospitalization for heart failure. MAIN OUTCOMES: Statements of patients with
      advanced heart failure, expressed in semi-structured interviews, concerning the
      quality of dying and medical decisions at the end of life. RESULTS: Many
      respondents only thought about death during exacerbations. Mentioned aspects of
      appropriate dying include: a degree of usefulness, prognostic knowledge,
      appropriate duration and mental awareness. Few respondents were in favour of
      euthanasia or suicide, but all wanted life-prolonging treatment to be withheld or
      withdrawn when appropriate. CONCLUSIONS: Our study found some elements of
      'appropriate dying' that differ from other studies and that are relatively
      specific for advanced heart failure. The tendency of patients not to think about
      death raises ethical concerns.

PMID- 15453629
TI  - A case series of inferior vena cava stenting for lower limb oedema in palliative
      care.
AB  - Inferior vena caval obstruction (IVCO) is an occasional cause of lower limb
      oedema in palliative care patients with metastatic malignancy. We present five
      cases who underwent IVC stenting for symptomatic relief. Four of the five cases
      had significant reduction in their oedema but three of these four patients died
      within two weeks of the procedure. The procedure itself is described and the
      appropriateness of this intervention in patients with end-stage disease is
      discussed.

PMID- 15453630
TI  - In-hospital death of cancer patients in a medical centre in Taiwan: comparison
      between hospice and acute wards.

PMID- 15453631
TI  - Repair of cytokine-induced DNA damage in cultured rat islets of Langerhans.
AB  - Treatment of cultured rat pancreatic islets of Langerhans with the combined
      cytokines interleukin-1beta (IL-1beta), interferon gamma (IFN gamma) and tumour
      necrosis factor alpha (TNF alpha) leads to DNA damage including strand breakage.
      We have investigated the nature of this damage and its repairability. When islets
      are further incubated for 4 h in fresh medium, the level of cytokine-induced
      strand breakage remains constant. If the nitric oxide synthase inhibitor N(G)
      monomethyl-L-arginine (NMMA) is present during cytokine treatment, then strand
      breakage is prevented. If NMMA is added following, rather than during,the
      cytokine treatment and islets are incubated for 4 h, further nitric oxide
      synthesis is prevented and most cytokine-induced strand breaks are no longer
      seen. To investigate DNA repair following cytokine treatment, cells were
      transferred to fresh medium and incubated for 4 h in the presence of hydroxyurea
      (HU) and 1-beta-D-arabinosyl cytosine (AraC), as inhibitors of strand rejoining.
      In the presence of these inhibitors there was an accumulation of strand breaks
      that would otherwise have been repaired. However, when further nitric oxide
      synthesis was inhibited by NMMA, significantly less additional strand breakage
      was seen in the presence of HU and AraC. We interpret this, as indicating that
      excision repair of previously induced base damage did not contribute
      significantly to strand breakage. Levels of oxidised purines, as indicated by
      formamidopyrimidine glycosylase (Fpg) sensitive sites, were not increased in
      cytokine-treated islets. We conclude that in these primary insulin-secreting
      cells: (a) the DNA damage induced by an 18h cytokine treatment is prevented by an
      inhibitor of nitric oxide synthase, (b) much of the damage is in the form of
      apparent strand breaks rather than altered bases such as oxidised purines, (c)
      substantial repair is ongoing during the cytokine treatment and this repair is
      not inhibited in the presence of nitric oxide.

PMID- 15453632
TI  - alpha-lipoic acid inhibits endotoxin-stimulated expression of iNOS and nitric
      oxide independent of the heat shock response in RAW 264.7 cells.
AB  - The heat shock response protects against sepsis-induced mortality, organ injury,
      cardiovascular dysfunction, and apoptosis. Several inducers of the heat shock
      response, such as hyperthermia, sodium arsenite, and pyrollidine dithiocarbonate,
      inhibit NF-kappaB activation and nitric oxide formation. The antioxidant lipoic
      acid (LA) has recently been found to inhibit NF-kappaB activation and nitric
      oxide formation. We therefore tested the hypothesis that LA induces a heat shock
      response. To test this hypothesis, we determined whether exposure to LA affects
      expression of both heat shock protein 70 (HSP-70) and nuclear heat shock factor-1
      (HSF-1) in lipopolysaccharide (LPS) stimulated macrophages. LA and hyperthermia
      attenuated LPS-induced increases in nuclear NF-kappaB, iNOS protein, and media
      nitrite concentrations. LPS and hyperthermia increased HSP-70 concentrations 8
      fold and 20-fold, respectively. No effect of LA treatment alone on HSP-70 protein
      expression was detected. Likewise, no effect of LA on HSF-1 protein expression
      was detected. These data suggest that LA inhibits LPS-induced activation of iNOS
      in macrophages independent of the heat shock response.

PMID- 15453633
TI  - The influence of extracorporeal circulation on the susceptibility of erythrocytes
      to oxidative stress.
AB  - Extracorporeal circulation (ECC), a necessary and integral part of cardiac
      surgery, can itself induce deleterious effects in patients. The pathogenesis of
      diffuse damage of several tissues is multifactorial. It is believed that
      circulation of blood extracorporeally through plastic tubes causes a whole body
      inflammatory response and a severe shear stress to blood cells. The aim of this
      study was to evaluate the level of oxidative stress and its deleterious effect on
      red blood cell (RBC) before (pre-ECC), immediately after (per-ECC) and 24 h after
      an ECC (24 h post-ECC). Several indicators of extracellular oxidative status were
      evaluated. The ascorbyl free radical (AFR) was directly measured in plasma using
      electron spin resonance (ESR) spectroscopy and expressed with respect to vitamin
      C levels in order to obtain a direct index of oxidative stress. Allophycocyanin
      assay was also used to investigate the plasma antioxidant status (PAS). Indirect
      parameters of antioxidant capacities of plasma such as vitamin E, thiol and uric
      acid levels were also quantified. RBC alterations were evaluated through
      potassium efflux and carbonyl levels after action of AAPH, a compound generating
      carbon centered free radicals. No changes in plasma uric acid and thiols levels
      were observed after ECC. However, vitamin E levels and PAS were decreased in per
      ECC and 24h post-ECC samples. Vitamin C levels were significantly lower in 24 h
      post-ECC and the AFR/ vitamin C ratio was increased. Differences in results had
      been noted when measurements took account of hemodilution. Increases of uric acid
      and thiols levels were observed after ECC. Vitamin E levels were not modified.
      However after hemodilution correction a significant decrease of vitamin C level
      was noted in 24 h post-ECC samples as compared to per-ECC sample. Whatever the
      way of measurement, vitamin C levels decreased suggesting the occurrence of ECC
      induced-oxidative stress. Concerning RBC, in the absence of AAPH, extracellular
      potassium remained unchanged between pre-, per- and 24 h post-ECC. AAPH induced a
      significant increase in extracellular potassium and carbonyls levels of RBC
      membranes, which was not modified by ECC. These results suggest the absence of
      alterations of RBC membrane during ECC despite the occurrence of disturbances in
      PAS. Such protection is of particular importance in a cell engaged in the
      transport of oxygen and suggests that RBC are equipped with mechanisms affording
      a protection against free radicals.

PMID- 15453634
TI  - Concentrations of pentosidine, an advanced glycation end-product, in umbilical
      cord blood.
AB  - Advanced glycation end-products (AGEs) are formed over several weeks to months by
      non-enzymatic glycation and oxidation ("glycoxidation") reactions between
      carbohydrate-derived carbonyl groups and protein amino groups, known as the
      Maillard reaction. Pentosidine is one of the best-characterized AGEs and is
      accepted as a satisfactory marker for glycoxidation in vivo. The present study
      was intended to measure pentosidine concentrations in umbilical cord blood from
      newborns with various gestational ages using our recently established high
      performance liquid chromatography method [Tsukahara, H. et al. (2003) Pediatr.
      Res. 54, 419-424]. Our study demonstrates, for the first time, that pentosidine
      is detected in most of the umbilical blood samples. This study also shows that
      the umbilical blood concentrations of pentosidine are considerably lower than
      normal adult values, but that they increase with gestation progression and fetal
      growth. Umbilical pentosidine concentrations were significantly elevated in
      newborns of mothers with preeclampsia compared to those of mothers without
      preeclampsia. We conclude that accumulation of AGEs and oxidative stress occurs
      in fetal tissues and organs in utero at the early stage of human life and that
      their accumulation is augmented in the maternal preeclampsic condition.

PMID- 15453635
TI  - Melatonin prevents oxidative stress and hepatocyte cell death induced by
      experimental cholestasis.
AB  - The induction of oxidative stress precedes liver injury during experimental
      obstructive jaundice (OJ). In this sense, different evidences suggest that
      melatonin (MEL), as antioxidant, may be useful in the protection against
      apoptosis and necrosis during experimental cholestasis. In addition, we will also
      assess if MEL-dependent protection is related to a recovery of antioxidant status
      disturbances induced by OJ. Cholestasis was achieved by double ligature and
      sectioning of the principal bile duct. MEL was injected intraperitoneally (500
      microg/kg/day). Lipid peroxidation was evaluated by the measurement of
      malondialdehyde (MDA) content in liver. Different parameters related to
      antioxidant status, such as reduced glutathione (GSH), glutathione peroxidase
      (GPx), catalase and superoxide dismutase (SOD) were determined in liver. Liver
      injury was assessed by alanine amino-transferase (ALT) in serum, histological
      examination, DNA fragmentation and TUNEL assay. The activation of perisinusoidal
      stellate cells was evaluated by immunohistochemical measurement of alpha-smooth
      muscle actin in liver sections. The induction of OJ increased all the parameters
      related to apoptosis and necrosis in liver. The induction of liver injury was
      associated with stellate cell activation, as well as an increase in MDA (p <
      0.0001) and a reduction in GSH, GPx, catalase and SOD content (p < 0.0001) in
      liver. MEL reduced hepatic apoptosis and necrosis (p < 0.004) with a significant
      improvement in all oxidative stress markers. In conclusion, our results showed
      that MEL recovered the antioxidant status and reduced apoptosis and necrosis
      induced by experimental cholestasis.

PMID- 15453636
TI  - Effect of aminoethylcysteine ketimine decarboxylated dimer, a natural sulfur
      compound present in human plasma, on tert-butyl hydroperoxide-induced oxidative
      stress in human monocytic U937 cells.
AB  - Aminoethylcysteine ketimine decarboxylated dimer (AECK-DD) is a natural sulphur
      compound present in human plasma and urine and in mammalian brain. Recently, it
      has been detected in many common dietary vegetables. The aim of the present study
      was to evaluate the ability of AECK-DD to affect cellular response of U937 human
      monocytic cells to tert-butyl hydroperoxide-induced oxidative stress. AECK-DD was
      incorporated into cells, as confirmed by GC-MS analyses, without any cytotoxic
      effect. A 24 h treatment with 50 and 250 microM AECK-DD resulted in the
      incorporation of 0.10 +/- 0.01 and 0.47 +/- 0.08ng AECK-DD x 10(6) cells,
      respectively. U937 cells pretreated with AECK-DD (in the range 4-100 microM)
      showed an increased resistance to tert-butyl hydroperoxide-induced necrotic
      death, as revealed by a higher percent of survival measured at all incubation
      times with respect to control cells. Moreover, the protective effect exhibited by
      AECK-DD is significantly stronger with respect to that obtained with other common
      antioxidants (N-acetyl cysteine and trolox) and comparable, although somewhat
      higher, to that of vitamin E. This effect seems to be due to the ability of AECK
      DD to reduce glutathione depletion and to inhibit lipid peroxidation during tert
      butyl hydroperoxide treatment. It can be concluded that AECK-DD protects cultured
      human monocytic cells against tert-butyl hydroperoxide-induced oxidative stress
      and subsequent cell death, likely through an antioxidant action inside the cell.
      Due to its presence in both human plasma and urine, AECK-DD may play a role in
      the modulation of oxidative processes in vivo.

PMID- 15453637
TI  - 1,4-dihydropyridines: reactivity of nitrosoaryl and nitroaryl derivatives with
      alkylperoxyl radicals and ABTS radical cation.
AB  - In the present paper, a direct quenching of radical species by a number of
      synthesized nitrosoaryl 1,4-dihydropyridines and their parent nitroaryl 1,4
      dihydropyridines was determined in aqueous media at pH 7.4. These two series of
      compounds were compared with the C-4 unsubstituted 1,4-dihydropyridines
      derivatives and the corresponding C-4 aryl substituted 1,4-dihydropyridines
      derivatives. Kinetic rate constants were assessed by UV-Vis spectroscopy.
      Nitrosoaryl derivatives were more reactive than the parent nitroaryl 1,4
      dihydropyridines. Our results strongly support the assumption that the reactivity
      between the synthesized 1,4-dihydropyridines derivatives with alkylperoxyl
      radicals involves electron transfer reactions, which is documented by the
      presence of pyridine as final product of reaction and the complete oxidation of
      the nitroso group to give rise the nitro group in the case of the nitrosoaryl 1,4
      dihydropyridines derivatives.

PMID- 15453638
TI  - Singlet oxygen-induced attenuation of growth factor signaling: possible role of
      ceramides.
AB  - Singlet oxygen, an electronically excited form of molecular oxygen, is a primary
      mediator of the activation of stress-activated protein kinases elicited by
      ultraviolet A (UVA; 320-400 nm). Here, the effects of singlet oxygen (1O2) on the
      extracellular signal-regulated kinase (ERK) 1/2 and Akt/protein kinase B pathways
      were analyzed in human dermal fibroblasts. While basal ERK 1/2 phosphorylation
      was lowered in cells exposed to either 1O2, UVA or photodynamic treatment, Akt
      was moderately activated by photochemically generated 1O2 in a phosphoinositide 3
      kinase (PI3K)-dependent fashion, resulting in the phosphorylation of glycogen
      synthase kinase-3 (GSK3). The activation of ERK 1/2 and Akt as induced by
      stimulation with epidermal growth factor (EGF) or platelet-derived growth factor
      (PDGF) was inhibited by 1O2 generated intracellularly upon photoexcitation of
      rose Bengal (RB). Photodynamic therapy (PDT)-induced apoptosis is known to be
      associated with increased formation of ceramides. Likewise, both 1O2 and UVA
      induced ceramide generation in human skin fibroblasts. The attenuation of EGF-
      and PDGF-induced activation of ERK 1/2 and Akt by 1O2 was mimicked by stimulation
      of fibroblasts with the cell-permeable C2-ceramide. Interestingly, EGF-induced
      tyrosine phosphorylation of the EGF receptor was strongly attenuated by 1O2 but
      unimpaired by C2-ceramide, implying that, although ceramide formation may mediate
      the above attenuation of ERK and Akt phosphorylation induced by 1O2, mechanisms
      beyond ceramide formation exist that mediate impairment of growth factor
      signaling by singlet oxygen. In summary, these data point to a novel mechanism of
      1O2 toxicity: the known 1O2-induced activation of proapoptotic kinases such as
      JNK and p38 is paralleled by the prevention of activation of growth factor
      receptor-dependent signaling and of anti-apoptotic kinases, thus shifting the
      balance towards apoptosis.

PMID- 15453639
TI  - A comparison of the effects of ocular preservatives on mammalian and microbial
      ATP and glutathione levels.
AB  - The aim of this study was to investigate the mechanism of action of the
      preservative sodium chlorite (NaClO2), and the relationship with intracellular
      glutathione depletion. A detailed comparison of the dose responses of two
      cultured ocular epithelial cell types and four species of microorganism was
      carried out, and comparisons were also made with the quaternary ammonium compound
      benzalkonium chloride (BAK), and the oxidant hydrogen peroxide (H2O2). The
      viability of mammalian and microbial cells was assessed in the same way, by the
      measurement of intracellular ATP using a bioluminescence method. Intracellular
      total glutathione was measured by reaction with 5,5'-dithiobis-2-nitrobenzoic
      acid in a glutathione reductase-dependent recycling assay. BAK and H2O2 caused
      complete toxicity to conjunctival and corneal epithelial cells at approximately
      25 ppm, in contrast to NaClO2, where > 100 ppm was required. The fungi Candida
      albicans and Alternaria alternata had a higher resistance to NaClO2 than the
      bacteria Staphyloccus aureus and Pseudomonas aeruginosa, but the bacteria were
      extremely resistant to H2O2. NaClO2 caused substantial depletion of intracellular
      glutathione in all cell types, at concentrations ranging from < 10 ppm in
      Pseudomonas, 25-100 ppm in epithelial cells, to > 500 ppm in fungal cells. The
      mechanisms of cytotoxicity of NaClO2, H2O2 and BAK all appeared to differ. NaClO2
      was found to have the best balance of high antibacterial toxicity with low ocular
      toxicity. The lower toxicity of NaClO2 to the ocular cells, compared with BAK and
      H2O2, is in agreement with fewer reported adverse effects of application in the
      eye.

PMID- 15453640
TI  - Vitamin E protects DNA from oxidative damage in human hepatocellular carcinoma
      cell lines.
AB  - Expression of multiple drug resistant (MDR) phenotype and over-expression of P
      glycoprotein (P-gp) in the human hepatocellular carcinoma (HCC) cell clone
      P1(0.5), derived from the PLC/PRF/5 cell line (P5), are associated with strong
      resistance to oxidative stress and a significant (p < 0.01) increase in
      intracellular vitamin E content as compared with the parental cell line. This
      study evaluates the role of vitamin E in conferring resistance to drugs and
      oxidative stress in P1(0.5) cells. Parental drug-sensitive cells, P5, were
      incubated in alpha-tocopherol succinate (alpha-TS, 5 microM for 24 h) enriched
      medium to increase intracellular vitamin E content to levels comparable to those
      observed in P1(0.5) cells at basal conditions. Susceptibility to lipid
      peroxidation and oxidative DNA damage were assessed by measuring the
      concentration of thiobarbituric-reactive substances (TBARS) and 8-hydroxy-2'
      deoxyguanosine (8-OHdG) at basal and after experimental conditions. Cell capacity
      to form colonies and resistance to doxorubicin were also studied. P5 cells,
      treated with alpha-TS, became resistant to ADP-Fe3+ and to ionizing radiation
      induced lipid peroxidation as P1(0.5) cells. Exposure to ADP-Fe3+ or ionizing
      radiation increased TBARS and the 8-OHdG content in the P5 cells, while vitamin E
      enrichment abolished these effects. Irradiation doses at 5 cGy increased TBARS
      and 8-OHdG. They also inhibited cell capacity to form colonies in the untreated
      P5 cells. Incubation with alpha-TS fully reverted this effect and significantly
      (p < 0.01) reduced the inhibitory effect of cell proliferation induced by
      irradiation doses at >500 cGy. Resistance to doxorubicin was not affected by
      alpha-TS. These observations demonstrate the role of vitamin E in conferring
      protection from lipid peroxidation, ionizing radiation and oxidative DNA damage
      on the human HCC cell line. They also rule out any role of P-gp over-expression
      as being responsible for these observations in cells with MDR phenotype
      expression.

PMID- 15453641
TI  - Hesperetin: a potent antioxidant against peroxynitrite.
AB  - Peroxynitrite (ONOO-) is a reactive oxidant formed from superoxide (*O2(-)) and
      nitric oxide (*NO), that can oxidize several cellular components, including
      essential protein, non-protein thiols, DNA, low-density lipoproteins (LDL), and
      membrane phospholipids. ONOO- has contributed to the pathogenesis of diseases
      such as stroke, heart disease, Alzheimer's disease, and atherosclerosis. Because
      of the lack of endogenous enzymes to thwart ONOO- activation, developing a
      specific ONOO- scavenger is remarkably important. In this study, the ability of
      hesperetin (3',5,7-trihydroxy-4-methoxyflavanone) to scavenge ONOO- and to
      protect cells against ONOO- and ROS was investigated. The data gained show that
      hesperetin can efficiently scavenge authentic ONOO- . In spectrophotometric
      analysis, the data revealed that hesperetin led to declined ONOO- -mediated
      nitration of tyrosine through electron donation. Hesperetin exhibited significant
      inhibition on the nitration of bovine serum albumin (BSA) by ONOO- in a dose
      dependent manner. Hesperetin also manifested cytoprotection from cell damage
      induced by ONOO- and ROS. The present study suggests that hesperetin is a
      powerful ONOO- scavenger and promotes cellular defense activity in the protection
      against ONOO- involved diseases.

PMID- 15453642
TI  - Global polio eradication initiative.

PMID- 15453643
TI  - Validation of neonatal tetanus elimination in Andhra Pradesh, India.

PMID- 15453644
TI  - African trypanosomiasis or sleeping sickness--fact-sheet.

PMID- 15453645
TI  - Preserving the educational environment.

PMID- 15453646
TI  - Advancements in dentistry: digital radiography and its application--Part III,
      resolution.

PMID- 15453647
TI  - Direct applications of a nanocomposite resin system: Part 1--The evolution of
      contemporary composite materials.
AB  - The delivery of functional, aesthetic restorations has been simplified by the
      introduction of contemporary composite materials. The most recent innovation in
      composite resin technology is the revolutionary application of nanocomposite
      theories in restorative materials. Contemporary nanocomposite materials deliver
      increased aesthetics, strength, and durability, combining scientific principles
      for increased longevity. This article discusses the application of nanocomposite
      resin systems and demonstrates the historical perspective of composite resin
      technologies in restorative treatment. The second installment to this series will
      address the clinical applications of such a system in the anterior region.
      LEARNING OBJECTIVES: This article addresses material selection considerations
      that must be addressed when selecting an appropriate direct restorative material.
      Upon reading this article, the reader should: Understand the historical
      background and application of nanocomposite materials. Be aware of the clinical
      implications of a nanocomposite resin system.

PMID- 15453648
TI  - Replacement of single missing molar teeth with dental implants.

PMID- 15453649
TI  - Simplifying the management of sequential dental loss with single-stage implants:
      a case study.

PMID- 15453650
TI  - Predictable provisionalization: achieving psychological satisfaction, form, and
      function.
AB  - The dentition is the foundation of the human face and is far more than just a
      masticatory apparatus. The smile, which is the definition of humankind, crosses
      all gender, age, cultural, and religious boundaries to express emotion. When
      enhancing or restoring a smile with aesthetic dentistry, the provisionalization
      phase is critical in conveying information regarding function, occlusion,
      phonetics, and the patient's expectations among the members of the restorative
      team. This presentation details a predictable process for rapidly fabricating
      provisional restorations with optimal fit and performance. LEARNING OBJECTIVES:
      This article describes the role of provisionalization and a protocol for
      fabrication of temporary prostheses for optimal results. Upon reading this
      article, the reader should: Understand the role of provisionalization on the
      surrounding soft and hard tissue structures. Recognize the role
      provisionalization plays in patient education and communication.

PMID- 15453651
TI  - Restoring the intraradicular space with direct composite resins: fiber-reinforced
      post-and-core system.

PMID- 15453652
TI  - Polymerization shrinkage of restorative composite resins.

PMID- 15453653
TI  - Five factors to be considered when restoring endodontically treated teeth.
AB  - Maintenance of tooth integrity and strength is critical to the longevity of any
      restoration. Endodontic treatment inherently requires reduction of supportive
      tooth structure to provide access and shape and clean the root canal system.
      Restorative modalities following root canal therapy must provide sufficient
      strength for the prosthetic material and tooth structures. This article presents
      several considerations in the treatment of endodontically compromised teeth to
      ensure clinical success. LEARNING OBJECTIVES: This article discusses relevant
      considerations in the restoration of endodontically treated teeth. Upon reading
      this article, the reader should: Understand the factors that affect the strength
      of an endodontically treated tooth. Recognize the available restorative options
      following root canal therapy.

PMID- 15453654
TI  - [As Mary, called to care].

PMID- 15453655
TI  - [The law of transplantation: (non-)pertinent questions].

PMID- 15453656
TI  - [Mental health and psychiatric nursing. Various contributions to its history in
      Portugal].

PMID- 15453657
TI  - [Globalization: risks and benefits].

PMID- 15453658
TI  - [Problems regarding the good in nursing practice].

PMID- 15453659
TI  - [Changes in sleep patterns in COPD. A new vital sign in the surveillance of
      individuals with chronic obstructive pulmonary disease].

PMID- 15453660
TI  - [Don't give up].

PMID- 15453661
TI  - [A day in orl/urol nursing at the Dona Estefania Hospital].

PMID- 15453662
TI  - [Alternatives to physical restraint in the elderly].

PMID- 15453663
TI  - [Irma Cecilia Maio. Advanced Nursing School of S. Vicente de Paulo].

PMID- 15453664
TI  - [Cycle of bioethics discussions. School of Medical Sciences of Lisbon].

PMID- 15453665
TI  - Effects of grain sampling procedures on fusarium mycotoxin assays in wheat
      grains.
AB  - Fusarium mycotoxins are increasingly studied agronomically, chemically, and
      pathologically in the context of food safety, as a means of preventing new major
      health crises. Reliable mycotoxin techniques and sampling procedures are required
      for assessment of the effects of different sources of variation on grain
      mycotoxin content in agronomic experiments. Analyses were performed with the aim
      of formulating guidelines for grain sampling to increase the reliability of grain
      mycotoxin measurement in agronomic experiments. Two toxins in wheat samples,
      deoxynivalenol and nivalenol, were targeted. With a nested linear mixed model, it
      was estimated that the uncertainty of nivalenol determination was low (+/-15
      microg/kg), whereas that for deoxynivalenol determination was higher (+/-38
      microg/kg). It was also found that grinding of the grain decreased the
      variability of the results. Moreover, despite the heterogeneity in grain
      mycotoxin content across a given field, it was shown that heads can be harvested
      manually for agronomic experiments provided that sampling is representative
      (evenly distributed over the entire plot area). Finally, delaying the assay until
      after harvest was found to affect the results obtained and should therefore be
      avoided.

PMID- 15453666
TI  - Discrimination of olives according to fruit quality using Fourier transform Raman
      spectroscopy and pattern recognition techniques.
AB  - Fourier transform Raman spectroscopy combined with pattern recognition has been
      used to discriminate olives of different qualities. They included samples of
      sound olives, olives with frostbite, olives that have been collected from the
      ground, fermented olives, and olive samples with diseases. Milled olives were
      measured in a dedicated sample cup, which was rotated during spectrum
      acquisition. A preliminary study of the data set structure was performed using
      hierarchical cluster analysis and principal component analysis. Two supervised
      pattern recognition techniques, K-nearest neighbors and soft independent modeling
      of class analogy (SIMCA), were tested using a "leave-a-fourth-out" cross
      validation procedure. SIMCA provided the best results, with prediction abilities
      of 95% for sound, 93% for frostbite, 96% for ground, and 92% for fermented
      olives. The olive samples with diseases (too few to define a class) were included
      in the validation and recognized as not belonging to any class. None of the
      damaged olive samples was wrongly predicted to the class of sound olives. With
      this approach a selection of sound olives for the production of high-quality
      virgin olive oil can be achieved.

PMID- 15453667
TI  - Quantitative examination of oxidized polyphenol-protein complexes.
AB  - We quantitatively examined interactions between polyphenols and proteins under
      oxidizing conditions, using radiolabeled 1,2,3,4,6-penta-O-galloyl-d
      glucopyranose (PGG) and bovine serum albumin (BSA) as model compounds. We tested
      NaIO(4), 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation
      (ABTS.+), and 2,2'-azobis(isobutyramidine) dihydrochloride (AAPH) as model
      oxidants and used sodium dodecyl sulfate to disrupt noncovalent PGG-BSA
      interactions after the oxidation. We used trichloroacetic acid to isolate the PGG
      BSA products after oxidation for radiochemical quantitation. NaIO(4) and ABTS.+
      oxidized PGG-BSA complexes more rapidly than AAPH. Using NaIO(4) as the oxidant,
      we found that soluble oxidized PGG-BSA complexes formed rapidly and were
      converted to insoluble complexes if PGG was present in excess over BSA.

PMID- 15453668
TI  - Early detection of fungal growth in bakery products by use of an electronic nose
      based on mass spectrometry.
AB  - This paper presents the design, optimization, and evaluation of a mass
      spectrometry-based electronic nose (MS e-nose) for early detection of unwanted
      fungal growth in bakery products. Seven fungal species (Aspergillus flavus,
      Aspergillus niger, Eurotium amstelodami, Eurotium herbariorum, Eurotium rubrum,
      Eurotium repens, and Penicillium corylophillum) were isolated from bakery
      products and used for the study. Two sampling headspace techniques were tested:
      static headspace (SH) and solid-phase microextraction (SPME). Cross-validated
      models based on principal component analysis (PCA), coupled to discriminant
      function analysis (DFA) and fuzzy ARTMAP, were used as data treatment. When
      attempting to discriminate between inoculated and blank control vials or between
      genera or species of in vitro growing cultures, sampling based on SPME showed
      better results than those based on static headspace. The SPME-MS-based e-nose was
      able to predict fungal growth with 88% success after 24 h of inoculation and 98%
      success after 48 h when changes were monitored in the headspace of fungal
      cultures growing on bakery product analogues. Prediction of the right fungal
      genus reached 78% and 88% after 24 and 96 h, respectively.

PMID- 15453669
TI  - NMR and HPLC-UV profiling of potatoes with genetic modifications to metabolic
      pathways.
AB  - Metabolite profiling has been carried out to assess the compositional changes
      occurring in potato tubers after genetic modifications have been made to
      different metabolic pathways. Most major features in the (1)H NMR and HPLC-UV
      profiles of tuber extracts have been assigned. About 40 GM lines and controls
      belonging to 4 groups of samples (derived from cv. Record or cv. Desiree and
      modified in primary carbon metabolism, starch synthesis, glycoprotein processing,
      or polyamine/ethylene metabolism) were analyzed. Differences were assessed at the
      level of whole profiles (by PCA) or individual compounds (by ANOVA). The most
      obvious differences seen in both NMR and HPLC-UV profiles were between the two
      varieties. There were also significant differences between two of the four
      Desiree GM lines with modified polyamine metabolism and their controls. Compounds
      notably affected were proline, trigonelline, and numerous phenolics. However,
      that modification gave rise to a very abnormal phenotype. Certain lines from the
      other groups had several compounds present in significantly higher or lower
      amounts compared to the control, but the differences in mean values amounted to
      no more than a 2-3-fold change: in the context of variability in the whole data
      set, such changes did not appear to be important.

PMID- 15453670
TI  - Determination of carotenoid stereoisomers in commercial dietary supplements by
      high-performance liquid chromatography.
AB  - A method for the determination of beta-carotene, lutein, and zeaxanthin including
      their cis-isomers and alpha-carotene in commercial dietary supplements by HPLC
      has been developed. The study comprises 11 oral dosage forms, including 9 soft
      gelatin capsules, 1 dragee, and 1 effervescent tablet formulation. The capsule
      content was extracted with an acetone-hexane mixture, and the gelatin shell was
      digested with papain to release carotenoids that had migrated into the coat.
      Sample preparation for tablets and dragees was carried out as described for the
      capsule content. Extraction recoveries exemplified for all-trans-beta-carotene
      and all-trans-lutein were 95 +/- 5% and 93 +/- 2%, and 95 +/- 2% and 79 +/- 5%
      after enzymatic treatment, respectively. Apart from all-trans-beta-carotene, its
      9-cis- and 13-cis-isomers were detected in all samples, whereas no evidence for
      cis-isomerization of lutein and zeaxanthin could be obtained. Migration of
      carotenoids into the shells was only observed in the case of beta-carotene. With
      the exception of one preparation, the beta-carotene contents determined exceeded
      the dosage specified on the label by up to 48%, which results from stability
      overages necessary to compensate for losses during storage.

PMID- 15453671
TI  - New mannose-binding lectin isolated from the rhizome of Sarsaparilla Smilax
      glabra Roxb. (Liliaceae).
AB  - A new mannose-binding lectin, designated SGM2, was isolated from the rhizome of a
      Chinese medicinal herb Smilax glabra (also known as sarsaparilla in general) by
      saline extraction, ammonium sulfate precipitation and fractionation, and affinity
      chromatography on fetuin- and mannose-agarose. SGM2 is shown to have a molecular
      mass of 37 kDa on gel filtration and 12.5 kDa on SDS-PAGE, indicating that it is
      a trimeric protein composed of three identical subunits. When the first 30 amino
      acid residues at the N-terminal were compared, SGM2 had approximately 40%
      homology with those of some other monocots. SGM2 had the property of
      hemagglutinating activity toward rabbit erythrocytes, which could be reversed by
      mannose and mannose polymers. SGM2 exhibited antiviral activities against both
      herpes simplex virus type 1 (HSV-1) and respiratory syncytial virus (RSV) with
      the same EC(50) of 8.1 microM.

PMID- 15453672
TI  - Anthraquinones isolated from Cassia tora (Leguminosae) seed show an antifungal
      property against phytopathogenic fungi.
AB  - The fungicidal activities of Cassia tora extracts and their active principles
      were determined against Botrytis cineria, Erysiphe graminis, Phytophthora
      infestans, Puccinia recondita, Pyricularia grisea, and Rhizoctonia solani using a
      whole plant method in vivo and were compared with synthetic fungicides and three
      commercially available anthraquinones. The responses varied with the plant
      pathogen tested. At 1 g/L, the chloroform fraction of C. tora showed a strong
      fungicidal activity against B. cinerea, E. graminis, P. infestans, and R. solani.
      Emodin, physcion, and rhein were isolated from the chloroform fraction using
      chromatographic techniques and showed strong and moderate fungicidal activities
      against B. cinerea, E. graminis, P. infestans, and R. solani. Furthermore, aloe
      emodin showed strong and moderate fungicidal activities against B. cinerea and R.
      solani, respectively, but did not inhibit the growth of E. graminis, P.
      infestans, P. recondita, and Py. grisea. Little or no activity was observed for
      anthraquinone and anthraquinone-2-carboxylic acid when tested at 1 g/L.
      Chlorothalonil and dichlofluanid as synthetic fungicides were active against P.
      infestans and B. cinerea at 0.05 g/L, respectively. Our results demonstrate the
      fungicidal actions of emodin, physcion, and rhein from C. tora.

PMID- 15453673
TI  - Relevance of carnosic acid concentrations to the selection of rosemary,
      Rosmarinus officinalis (L.), accessions for optimization of antioxidant yield.
AB  - Methods were developed to identify and select accessions of rosemary, Rosmarinus
      officinalis (L.), producing optimum antioxidant activity. Extracts from 12
      different rosemary accessions, using three solvents of varying polarity, were
      assayed for their antioxidant activity, and their major antioxidant compounds
      were identified and quantified by high-performance liquid chromatography (HPLC).
      Carnosic acid concentrations were correlated with (i) the free radical scavenging
      activity of these extracts, as measured by the 2,2-diphenyl-1-picrylhydrazyl
      assay (adjusted R(2) = 77.3%) and (ii) their inhibition of linoleic acid
      oxidation, as measured by the beta-carotene assay (adjusted R(2) = 44.1%). The
      correlation was broadly confirmed by the production of volatile aldehydes as
      measured by the hexanal assay. The variation of carnosic acid concentrations in
      extracts of 29 accessions, grown in field trials at three sites in England, was
      determined.

PMID- 15453674
TI  - Phytochemicals and antioxidant properties in wheat bran.
AB  - Bran samples of seven wheat varieties from four different countries were examined
      and compared for their phytochemical compositions and antioxidant activities.
      Phenolic acid composition, tocopherol content, carotenoid profile, and total
      phenolic content were examined for the phytochemical composition of wheat bran,
      whereas the measured antioxidant activities were free radical scavenging
      properties against 2,2-diphenyl-1-picrylhydrazyl radical, radical cation 2,2'
      azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt, peroxide
      radical anion O(2)(.-), and oxygen radical and chelating capacities. The results
      showed that the tested wheat bran samples differed in their phytochemical
      compositions and antioxidant properties. Ferulic acid, with a concentration range
      of 99-231 microg/g, was the predominant phenolic acid in all of the tested bran
      samples and accounted for about 46-67% of total phenolic acids on a weight basis.
      The concentrations for alpha-, delta-, and gamma- tocopherols were 1.28-21.29,
      0.23-7.0, and 0.92-6.90 microg/g, respectively. In addition, lutein and
      cryptoxanthin were detected in all of the tested bran samples with levels of 0.50
      1.80 and 0.18-0.64 microg/g, respectively. Zeaxanthin was detected in the six
      bran samples, and the greatest zeaxanthin concentration of 2.19 microg/g was
      observed in the Australian general purpose wheat bran. Beta-carotene was detected
      in four of the tested bran samples at a range of 0.09-0.40 microg/g. These data
      suggest that wheat and wheat bran from different countries may differ in their
      potentials for serving as dietary sources of natural antioxidants.

PMID- 15453675
TI  - Isolation and properties of a Kunitz-type protein inhibitor obtained from
      Pithecellobium dulce seeds.
AB  - We report for the first time the isolation and characterization of a protease
      inhibitor from the seeds of Pithecellobium dulce, which is a Leguminosae tree
      native to Mexico. The purification of the P. dulce trypsin inhibitor (PDTI) was a
      direct process. After its extraction (pH 8.0) and precipitation (80%
      (NH(4))(2)SO(4)), the pH was adjusted to 4.0, the supernatant was loaded onto a
      CM-Sepharose column, and a single peak of trypsin inhibitory activity was eluted
      (CM-TIA). The main component of CM-TIA was PDTI, a protein composed of two
      polypeptide chains joined by disulfide bridge(s), with a pI of 4.95 and a
      molecular weight determined by electrospray mass spectrometry of 19 614 Da. The N
      terminal sequence of PDTI has the highest similarity with the seed inhibitor of
      Acacia confusa. PDTI lacks chymotrypsin inhibitory activity. A low rate of
      cytotoxicity of CM-TIA toward RINm5F cells contrasted with a high rate of the
      active fraction G75-TIA (gel filtration chromatography; LC(50) of 0.04 mg/mL).

PMID- 15453676
TI  - Effects of commercial anthocyanin-rich extracts on colonic cancer and
      nontumorigenic colonic cell growth.
AB  - Commercially prepared grape (Vitis vinifera), bilberry (Vaccinium myrtillus L.),
      and chokeberry (Aronia meloncarpa E.) anthocyanin-rich extracts (AREs) were
      investigated for their potential chemopreventive activity against colon cancer.
      The growth of colon-cancer-derived HT-29 and nontumorigenic colonic NCM460 cells
      exposed to semipurified AREs (10-75 microg of monomeric anthocyanin/mL) was
      monitored for up to 72 h using a sulforhodamine B assay. All extracts inhibited
      the growth of HT-29 cells, with chokeberry ARE being the most potent inhibitor.
      HT-29 cell growth was inhibited approximately 50% after 48 h of exposure to 25
      microg/mL chokeberry ARE. Most importantly, the growth of NCM460 cells was not
      inhibited at lower concentrations of all three AREs, illustrating greater growth
      inhibition of colon cancer, as compared to nontumorigenic colon cells. Extracts
      were semipurified and characterized by high-pressure liquid chromatography,
      spectrophotometry, and colorimetry. Grape anthocyanins were the glucosylated
      derivatives of five different anthocyanidin molecules, with or without p-coumaric
      acid acylation. Bilberry contained five different anthocyanidins glycosylated
      with galactose, glucose, and arabinose. Chokeberry anthocyanins were cyanidin
      derivatives, monoglycosylated mostly with galactose and arabinose. The varying
      compositions and degrees of growth inhibition suggest that the anthocyanin
      chemical structure may play an important role in the growth inhibitory activity
      of commercially available AREs.

PMID- 15453677
TI  - Sensitive PCR analysis of animal tissue samples for fragments of endogenous and
      transgenic plant DNA.
AB  - An optimized DNA extraction protocol for animal tissues coupled with sensitive
      PCR methods was used to determine whether trace levels of feed-derived DNA
      fragments, plant and/or transgenic, are detectable in animal tissue samples
      including dairy milk and samples of muscle (meat) from chickens, swine, and beef
      steers. Assays were developed to detect DNA fragments of both the high copy
      number chloroplast-encoded maize rubisco gene (rbcL) and single copy nuclear
      encoded transgenic elements (p35S and a MON 810-specific gene fragment). The
      specificities of the two rbcL PCR assays and two transgenic DNA PCR assays were
      established by testing against a range of conventional plant species and
      genetically modified maize crops. The sensitivities of the two rbcL PCR assays
      (resulting in 173 and 500 bp amplicons) were similar, detecting as little as 0.08
      and 0.02 genomic equivalents, respectively. The sensitivities of the p35S and MON
      810 PCR assays were approximately 5 and 10 genomic equivalents for 123 bp and 149
      bp amplicons, respectively, which were considerably less than the sensitivity of
      the rbcL assays in terms of plant cell equivalents, but approximately similar
      when the higher numbers of copies of the chloroplast genome per cell are taken
      into account. The 173 bp rbcL assay detected the target plant chloroplast DNA
      fragment in 5%, 15%, and 53% of the muscle samples from beef steers, broiler
      chickens, and swine, respectively, and in 86% of the milk samples from dairy
      cows. Reanalysis of new aliquots of 31 of the pork samples that were positive in
      the 173 bp rbcL PCR showed that 58% of these samples were reproducibly positive
      in this same PCR assay. The 500 bp rbcL assay detected DNA fragments in 43% of
      the swine muscle samples and 79% of the milk samples. By comparison, no
      statistically significant detections of transgenic DNA fragments by the p35S PCR
      assay occurred with any of these animal tissue samples.

PMID- 15453678
TI  - Production of bioavailable flavonoid glucosides in fruit juices and green tea by
      use of fungal alpha-L-rhamnosidases.
AB  - Flavonoid glucosides have been reported to be more bioavailable than their
      rutinoside counterparts. The aim of this study is to describe a first step in the
      use of alpha-L-rhamnosidases (RhaA and RhaB) from Aspergillus aculeatus as a way
      to produce functional beverages based on their potentially increased flavonoid
      bioavailability. Blackcurrant juice (BCJ), orange juice (OJ), and green tea
      infusion (GT) were incubated with either RhaA or RhaB at 30 degrees C for 10 h.
      Aliquots of controls and enzyme-treated samples were taken at different time
      points and analyzed by high-performance liquid chromatography-photodiode-array
      detector-mass spectrometry of daughter fragments (HPLC-DAD-MS-MS). Both RhaA and
      RhaB selectively catalyze in situ the removal of terminal rhamnosyl groups in the
      three beverages despite the heterogeneity of assay conditions such as different
      rutinosides and pH. Incubation of the three beverages with the two rhamnosidases
      resulted in a hyperbolic decrease in the flavonoid rutinosides (anthocyanins in
      BCJ, flavanones in OJ, and flavonols in GT) and a concomitant increase in their
      flavonoid glucoside counterparts. The time required for conversion of 50% of the
      rutinoside into the corresponding flavonoid glucoside ranged from 30 min (RhaB
      rutin in GT) to 6 h (RhaB-delphinidin 3-rutinoside in BCJ). The results presented
      in this paper are a step forward in the use of enzyme-treated beverages as a
      source of bioavailable flavonoid glucosides.

PMID- 15453679
TI  - Study on furundu, a traditional Sudanese fermented roselle (Hibiscus sabdariffa
      L.) seed: effect on in vitro protein digestibility, chemical composition, and
      functional properties of the total proteins.
AB  - Furundu, a meat substitute, is traditionally prepared by cooking the karkade
      (Hibiscus sabdariffa L.) seed and then fermenting it for 9 days. Physicochemical
      and functional properties of raw and cooked seed and of furundu ferments were
      analyzed. Furundu preparation resulted in significant changes in karkade seed
      major nutrients. Total polyphenols and phytic acid were also reduced. The
      increase in total acidity and fat acidity coupled with a decrease in pH indicates
      microbial hydrolysis of the major nutrients; proteins, carbohydrates, and fats.
      In vitro digestibility of the seed proteins reached the maximum value (82.7%) at
      the sixth day of fermentation, but thereafter it significantly decreased. The
      effect of furundu preparation on N solubility profiles and functional properties,
      such as emulsification and foaming properties and other related parameters, is
      investigated in water and in 1 M NaCl extracts from defatted flour samples. The
      results show that cooking followed by fermentation affects proteins solubility in
      water and 1 M NaCl. The foaming capacity (FC) from the flour of raw seed
      decreased as a result of cooking. Fermentation for 9 days significantly increased
      the FC of the cooked seed, restoring the inherent value. Foam from fermented
      samples collapsed more rapidly during a period of 120 min as compared to the foam
      from raw and cooked karkade seeds; stability in 1 M NaCl was lower as compared to
      those in water. In water, the emulsion stability (ES) from the fermented samples
      was significantly higher than that of the raw seed flour. Addition of 1 M NaCl
      significantly decreased the ES of the fermented samples.

PMID- 15453680
TI  - Stable free radicals and peroxyl radical trapping capacity in red wines.
AB  - Thirty-two experimental red wines, obtained from eight cultivars and aged in
      bottles for 2 and 7 years, were examined for the presence of stable free radicals
      (SFR), for the peroxyl radical trapping capacity (PRTC), and for the
      concentrations of some important polyphenol families. Aging significantly
      increases SFR, polyphenol polymers with n > or = 5 (HMWP), and PRTC and is
      accompanied by a strong decrease of free anthocyanins. Multivariate regression
      analyses show that HMWP and SFR are independently associated with PRTC while HMWP
      and anthocyanins are independently associated with the formation of SFR. These
      results indicate that polymeric polyphenols generated from anthocyanins and
      proanthocyanidins during wine aging are able to convert highly reactive free
      radicals into nonreactive radicals through electron delocalization. The strict
      correlation between SFR and antioxidant activity that we found suggests that
      these characteristics are related to the functional properties of food.

PMID- 15453681
TI  - Instability of St. John's wort (Hypericum perforatum L.) and degradation of
      hyperforin in aqueous solutions and functional beverage.
AB  - Several bioactive botanicals including St. John's wort (SJW; Hypericum perforatum
      L.) have been used to formulate functional foods and beverages. This study aimed
      to investigate the stability of SJW components in aqueous solutions and fruit
      flavored drinks. Changes of active marker components (hypericin, pseudohypericin,
      hyperforin, and adhyperforin) as affected by pH and light exposure were
      determined by HPLC, and the degradation of hyperforin was analyzed by LC-MS/MS
      and NMR. SJW components were found to be unstable in acidic aqueous solutions.
      More changes occurred under light exposure, with hyperforin and adhyperforin
      decreasing the most. Less severe changes were observed in the drink sample as
      compared to the pH 2.65 solution. Major degradation products of hyperforin in
      acidic aqueous solutions were identified as furohyperforin, furohyperforin
      hydroperoxide, and furohyperforin isomer a. The latter was also found in the
      drink product containing SJW as an ingredient. Biological activities and
      potential quality and safety implications of these chemical changes are yet to be
      evaluated.

PMID- 15453682
TI  - Biodegradation of 3-chloro-1,2-propanediol with Saccharomyces cerevisiae.
AB  - A novel enzymatic dehalogenating activity of 3-chloro-1,2-propanediol (3-MCPD)
      with Saccharomyces cerevisiae (baker's yeast) is reported. All bioconversion
      assays were carried out under aerobic conditions, at 28 degrees C, and the
      kinetics were monitored. The biodegradation was performed at different pH values
      (6.2, 7.0, and 8.2), in the presence and absence of glucose, using racemic 3-MCPD
      at two different concentrations (7.3 micromol/L and 27 mmol/L). Optimal
      conversion (68%) of racemic (R,S)-3-MCPD at a concentration of 27 mmol/L was
      achieved after 48 h of reaction time, at pH 8.2, and in the presence of glucose.
      At a concentration of 7.3 micromol/L, 73% degradation was observed after 72 h, at
      pH 8.2 and in the absence of glucose. Under the same experimental conditions, the
      conversion of pure (S)-3-MCPD (85%) was higher than that of the (R)-enantiomer
      (60%).

PMID- 15453683
TI  - Physicochemical characterization of a new pineapple hybrid (FLHORAN41 Cv.).
AB  - The physicochemical characteristics (pH, total and soluble solids, and titratable
      acidity), sugars, organic acids, carotenoids, anthocyanins, volatile compounds,
      and cell wall polysaccharides of a new pineapple hybrid (FLHORAN41 cultivar) were
      measured throughout maturation and compared with the Smooth Cayenne cv. At full
      maturity, the FLHORAN41 cv. has a higher titratable acidity and soluble solids
      content than the Smooth Cayenne cv. The golden yellow flesh and red-orange to
      scarlet shell of ripe FLHORAN41 cv. fruits are due to carotenoid and anthocyanin
      levels that are, respectively, 2.5 and 1.5 times higher than those of the flesh
      and shell of the ripe Smooth Cayenne cv., respectively. During maturation of the
      FLHORAN41 cv., there was an increase in all classes of aroma compounds (mainly
      terpene hydrocarbons and esters), although their relative proportions were
      similar in both cultivars at full maturity. Cell wall polysaccharides undergo
      little change during maturation.

PMID- 15453684
TI  - Identification and quantification of phenolic compounds in berries of Fragaria
      and Rubus species (family Rosaceae).
AB  - High-performance liquid chromatography combined with diode array and electrospray
      ionization mass spectrometric detection was used to study soluble and insoluble
      forms of phenolic compounds in strawberries, raspberries (red and yellow
      cultivated and red wild), arctic bramble, and cloudberries. Hydroxycinnamic acids
      were present as free forms in cloudberries and mainly as sugar esters in the
      other berries. Quercetin 3-glucuronide was the typical flavonol glycoside in all
      of the berries studied. The composition of the predominant anthocyanins can be
      used to distinguish the studied red Rubus species from each other since cyanidin
      was glycosylated typically with 3-sophorose (56%) in cultivated red raspberry,
      with 3-sophorose (30%) and 3-glucose (27%) in wild red raspberry, and with 3
      rutinose (80%) in arctic bramble. Ellagic acid was present as free and
      glycosylated forms and as ellagitannins of varying degrees of polymerization.
      Comparable levels of ellagitannins were obtained by the analysis of soluble
      ellagitannins as gallic acid equivalents and by the analysis of ellagic acid
      equivalents released by acid hydrolysis of the extracts.

PMID- 15453685
TI  - Free and conjugated biogenic amines in green and roasted coffee beans.
AB  - This work reports the composition of arabica and robusta coffees in terms of
      biogenic amines. The analyses were conducted before and after acid hydrolysis
      with the aim of the determining both free and conjugated forms in green and
      roasted coffee beans. The amines (putrescine, cadaverine, serotonin, tyramine,
      spermidine, and spermine) were determined by reverse-phase high-performance
      liquid chromatography (RP-HPLC) after derivatization with dansyl chloride.
      Multivariate analyses were applied in order to evaluate the possible use of these
      amines as chemical descriptors for arabica and robusta coffees. It was found that
      putrescine, the main biogenic amine present in the green beans, could be used in
      the discrimination of the referred species. There is also some evidence that
      these compounds can be used for discrimination between green coffees subjected to
      different postharvest processes and that tyramine can be considered a chemical
      marker for Angolan robustas. The variations in biogenic amine levels after roasts
      is also discussed, but the statistical significance for species discrimination is
      reduced.

PMID- 15453686
TI  - Chemical composition and protein quality comparisons of soybeans and soybean
      meals from five leading soybean-producing countries.
AB  - Soybeans (SBs) were obtained from five leading SB-producing countries (Argentina,
      Brazil, China, India, and the United States), imported to the United States, and
      processed into soybean meal (SBM) under uniform conditions in the United States.
      SBs from China had the highest crude protein (CP) content while SBs and the
      resultant SBM from Argentina had the lowest. Additional differences in the
      quality of the SB and resultant SBM samples collected were noted. An additional
      set of SBM produced in these five countries and subjectively evaluated to be of
      low, intermediate, and high quality also were obtained and evaluated. Overall,
      SBM quality affected amino acid and mineral concentrations with differences
      existing both among and within countries. SBM produced in the United States had a
      higher CP content than SBM produced in other countries. Amino acid concentrations
      generally increased, and antinutritional factors decreased with increasing
      subjective quality assessment.

PMID- 15453687
TI  - The dissipation of tebuconazole and propiconazole in boronia (Boronia megastigma
      Nees).
AB  - The broad spectrum, systemic fungicides tebuconazole and propiconazole are used
      to control rust in boronia (Boronia megastigma Nees). Gas chromatography combined
      with either a benchtop quadrupole mass spectrometer or a high-resolution mass
      spectrometer allowed for the monitoring of both pesticides in boronia leaves,
      flowers, and concrete. Field trials were established at two sites to determine
      the rate of dissipation of tebuconazole and propiconazole in boronia. At site 1,
      two application rates of 125 and 250 g active ingredient/hectare (ai/ha)
      tebuconazole were employed. Treatments were repeated 17 days later. At harvest,
      286 days after the final application, tebuconazole was detected at levels of 0.06
      +/- 0.05 and 0.5 +/- 0.1 [mg/kg +/- standard error, on a dry matter basis (DMB)]
      in the leaves collected from plots treated with 125 and 250 g ai/ha of
      tebuconazole, respectively. The oil produced from the flowers collected at the
      final harvest had residues of tebuconazole at levels of 0.06 +/- 0.03 and 0.10 +/
      0.08 mg/kg for the 125 and 250 g ai/ha application rates, respectively. Two
      repeat applications of 125 g ai/ha propiconazole were also used at site 1.
      Residues of propiconazole were detected at 0.09 +/- 0.03 mg/kg (DMB) 286 days
      after the final application. At site 2, treatments of 125 g ai/ha of tebuconazole
      were applied twice. At harvest, 279 days after the final application of
      tebuconazole, residues were recorded at 0.30 +/- 0.09 mg/kg in the leaves (DMB)
      while the oil produced had 0.20 +/- 0.07 mg/kg.

PMID- 15453688
TI  - Milk excretion of ivermectin and moxidectin in dairy sheep: assessment of drug
      residues during cheese elaboration and ripening period.
AB  - Ivermectin (IVM) and moxidectin (MXD) are broad-spectrum endectocide
      antiparasitic drugs extensively used in food-producing animals. The patterns of
      IVM and MXD excretion in milk were comparatively characterized following their
      subcutaneous administration (200 microg.kg(-1) of body weight) to lactating dairy
      sheep. The relationship between milk excretion and plasma disposition kinetics of
      both compounds was characterized. A pool of milk collected from all of the
      animals in each experimental group was used for cheese elaboration. IVM and MXD
      residual concentrations were assessed during the cheese-making process and
      ripening period. IVM and MXD concentrations were measured in plasma, milk, and
      milk product (whey, curd, and cheese) samples using an HPLC-based methodology
      with fluorescence detection. IVM and MXD were extensively distributed from the
      bloodstream to the mammary gland, and large quantities, particularly of MXD, were
      excreted in milk. Residual concentrations of both compounds were recovered in
      milk up to 30 (IVM) and 35 (MXD) days post-treatment. The total fraction of the
      administered dose excreted in milk for MXD was significantly higher than that of
      IVM. During cheese production, the highest residual concentrations of both
      molecules were measured in the curd. Thirty-four percent of the total drug
      residue measured in the pooled milk collected from treated sheep was lost during
      the cheese-making process. The lowest residual concentrations were measured in
      the whey. IVM and MXD concentrations in the elaborated cheese tended to increase
      during the ripening period, reaching the highest residual level at 40 days of
      cheese maturation. The long persistence of milk residual concentrations of MXD
      and IVM in lactating dairy sheep and the high concentrations found in cheese and
      other milk-related products should be seriously considered before recommendation
      of the extralabel use of these antiparasitic drugs in dairy animals.

PMID- 15453689
TI  - Hydrolysis of glycosidically bound volatiles from apple leaves (Cv. Anna) by
      Aspergillus niger beta-glucosidase affects the behavior of codling moth (Cydia
      pomonella L.).
AB  - Glycosidically bound volatiles released from apple leaf extracts (cv. Anna) were
      analyzed by solid-phase microextraction-gas chromatography-mass spectrometry
      (SPME-GC-MS) and their behavioral effects on codling moth (CM) adults were
      evaluated in cage bioassays. The levels of 1-octanol, linalool, geraniol, benzyl
      alcohol, methyl salicylate, (2R,5R)-theaspirane, and (2S,5R)-theaspirane were
      significantly increased in the leaf extracts containing the Aspergillus niger
      beta-glucosidase (BGL1) compared to the extracts containing the glucoimidazole.
      The attractiveness of individual compounds to CM adults was found in the
      following decreasing order: methyl salicylate and mixture of two theaspirane
      isomers, followed by linalool and benzyl alcohol. Geraniol was found to be
      repellent to CM adults. The addition of geraniol (39.4 ng mL(-1)) to any of the
      individual volatiles or to a mixture of these attractants eliminated their
      attractiveness. Our data suggest the possible application of geraniol as a
      repellent and methyl salicylate or theaspiranes as attractants for the integrated
      control of CM in apple orchards.

PMID- 15453690
TI  - Leaching of pesticides from biobeds: effect of biobed depth and water loading.
AB  - Pesticides may be released to farmyard surfaces as a result of spillages,
      leakages, and the decontamination of tractors and sprayers. Biobeds can be used
      to intercept and treat contaminated runoff, thus minimizing losses to the
      environment. Previous studies using lined and unlined biobeds showed that water
      management was the limiting factor for both systems. While lined biobeds
      effectively retained pesticides, the system rapidly became water logged and
      degradation was slow. Studies using unlined biobeds showed that >99% of the
      applied pesticides were removed by the system, with a significant proportion
      degraded within 9 months. However, peak concentrations of certain pesticides (Koc
      < 125) were unacceptable to the regulatory authorities. These experiments were
      designed to optimize the design and management of unlined biobeds. Experiments
      performed to investigate the relationship between biobed depth and water loading
      showed that biobeds need to have a minimum depth of 1-1.5 m. The surface area
      dimension of the biobed depends on the water loading, which is controlled by the
      nature and frequency of pesticide handling activities on the farm. Leaching
      losses of all but the most mobile (Koc < 15) pesticides were <0.32% of the
      applied dose from 1.5 m deep biobeds subject to a water loading of 1175 L m(-2).
      These were reduced to <0.06% when a water loading of 688 L m(-2) was applied and
      down to <0.0001% for a water loading of 202 L m(-2). On the basis of these data,
      a 1.5 m deep biobed, subject to a maximum water loading of 1121 L m(-2) and with
      a surface area of 40 m(2) should be able to treat < or =44000 L of pesticide
      waste and washings such that the average concentration of all pesticides, other
      than those classified as very mobile, does not exceed 5 microg L(-1). This level
      of treatment can be improved by further reduction in the hydraulic loading.

PMID- 15453691
TI  - Phototransformation of carboxin in water. Toxicity of the pesticide and its
      sulfoxide to aquatic organisms.
AB  - Sunlight exposure of aqueous suspensions of carboxin (1) causes its
      phototransformation to sulfoxide 2 and minor components. Similar effects are
      observed in the presence of humic acid or nitrate or at different pH values.
      Photoproducts 2-9 were isolated by chromatographic techniques and/or identified
      by spectroscopic means. Carboxin 1 and its main photoproduct sulfoxide 2 were
      tested to evaluate acute toxicity to primary consumers typical of the aquatic
      environment: the rotifer Brachionus calyciflorus and two crustaceans, Daphnia
      magna and Thamnocephalus platyurus. Chronic tests comprised a producer, the alga
      Pseudokirchneriella subcapitata, and a consumer, the crustacean Ceriodaphnia
      dubia.

PMID- 15453692
TI  - Isomer selectivity in aquatic toxicity and biodegradation of cypermethrin.
AB  - Synthetic pyrethroids (SPs) are widely used in both agricultural and urban
      regions for insect control. Unlike many other pesticides, SPs are chiral
      compounds consisting of stereoisomers. However, occurrence of isomer selectivity
      in environmental processes is poorly understood for SPs. We evaluated isomer
      selectivity in toxicity of cypermethrin (CP) to Ceriodaphnia dubia and in its
      biodegradation by microbial isolates and in sediment. Among the eight
      enantiomers, two enantiomers (1R-cis-alphaS and 1R-trans-alphaS) were found to be
      toxic to C. dubia. Bacteria strains isolated from sediment selectively degraded
      CP diastereomers and enantiomers. The trans diastereomers were preferentially
      degraded over the cis diastereomers. Of the two active enantiomers, 1R-cis-alphaS
      was degraded slower, whereas 1R-trans-alphaS was degraded faster than the other
      stereoisomers. Similar isomer selectivity was observed during CP degradation in
      whole sediment. Since ecotoxicity is likely caused only by the biologically
      active enantiomers, knowledge on isomer selectivity may improve our understanding
      of the ecological risks of CP and analogous SPs.

PMID- 15453693
TI  - Degradation and adsorption of fosthiazate in soil.
AB  - Adsorption and degradation behavior of a pesticide in soil has a strong effect on
      its environmental fate as well as efficacy for pest control. Fosthiazate is an
      organophosphate compound that is currently under development as a nonfumigant
      nematicide. In this study, we evaluated adsorption and degradation kinetics of
      fosthiazate in three U.S. soils with different properties. Adsorption of
      fosthiazate in mineral soil was negligibly weak but appeared to increase with
      soil organic matter (OM) content. The half-life (T(1/2)) of fosthiazate ranged
      from 0.5 to 1.5 months in nonsterile soils but was prolonged to 1-3 months after
      sterilization. Degradation of fosthiazate in soil appeared to be caused by both
      chemical and microbial transformations. The persistence of fosthiazate generally
      decreased with increasing soil pH, but increased with increasing soil OM and clay
      contents. This results suggest that fosthiazate may have an enhanced leaching
      potential in acidic soils with low OM content, and its efficacy in high pH soils
      may not last as long as in neutral soils because of faster degradation.

PMID- 15453694
TI  - Relationship between procyanidin and flavor contents of cocoa liquors from
      different origins.
AB  - The flavor of eight cocoa liquors of different origins (Africa, America, and
      Asia) and different varieties (Fine grades: criollo, trinitario, and nacional.
      Bulk-basic grade: forastero.) was analyzed by headspace solid-phase
      microextraction mass spectrometry (HS-SPME-MS). Their procyanidin contents were
      quantified by HPLC-UV (280 nm). Fine varieties with short fermentation processes
      proved to contain more procyanidins, while criollo from New Guinea and forastero
      beans showed the highest aroma levels. The levels of cocoa aroma compounds formed
      during roasting are shown to vary directly with bean fermentation time and
      inversely with residual procyanidin content in cocoa liquor. Measurement of
      antioxidant activity in cocoa liquor proved to be a useful tool for assessing
      residual polyphenols.

PMID- 15453695
TI  - Flavor characterization of ripened cod roe by gas chromatography, sensory
      analysis, and electronic nose.
AB  - Characterization of the flavors of ripened roe products is of importance to
      establish a basis for a standardized product. Flavor profiles of commercially
      processed ripened roe from Iceland and Norway were studied by sensory analysis,
      gas chromatography-olfactometry (GC-O), gas chromatography-mass spectrometry (GC
      MS), and an electronic nose to characterize the headspace of ripened roe. Sensory
      analysis showed that ripened roe odor and flavor in combination with caviar
      flavor and whey/caramel-like odor give the overall positive effect of the complex
      characteristic roe flavor. Analysis of volatiles by GC-MS and electronic nose
      confirmed the presence of aroma compounds contributing to the typical ripening
      and spoilage flavors detected by the sensory analysis. Methional, 1-octen-3-ol,
      and 2,6-nonadienal were the most important compounds contributing to ripened roe
      odor. Spoilage flavors were partly contributed by 3-methyl-1-butanol and 3
      methylbutanal, which can be measured by the electronic nose and are suggested as
      quality indicators for objectively assessing the ripening of roe. Principal
      component analysis of the overall data showed that GC-O correlated well with
      sensory evaluation and the electronic nose measurements.

PMID- 15453696
TI  - Effect of fat nature and aroma compound hydrophobicity on flavor release from
      complex food emulsions.
AB  - Complex food emulsions containing either hydrogenated palm kernel oil (vegetable
      fat) or anhydrous milk fat (animal fat) were flavored by using different aroma
      compounds. The fats differed by their fatty acid and triacylglycerol compositions
      and by their melting behavior, while the aroma compounds (ethyl butanoate, ethyl
      hexanoate, methyl hexanoate, mesifurane, linalool, diacetyl, cis-3-hexen-1-ol,
      and gamma-octalactone) differed by their hydrophobicity. Application of
      differential scanning calorimetry to fat samples in bulk and emulsified forms
      indicated differences in the ratio of solid-to-liquid between temperatures
      ranging from 10 to 35 degrees C. Solid-phase microextraction coupled with GC-MS
      analysis indicated that flavor release from food emulsions containing animal or
      vegetable fat differed depending on both the fat nature and flavor compound
      hydrophobicity. The release of diacetyl was higher for emulsions containing
      animal fat, whereas the release of esters was higher for emulsions containing
      vegetable fat. The release of cis-3-hexenol, linalool, gamma-octalactone, and
      mesifurane (2,5-dimethyl-4-methoxy-(2H)-furan-3-one) was very similar for the two
      fatty systems. The above results were discussed not only in terms of aroma
      compound hydrophobicity, but also in terms of structural properties of the
      emulsions as affected by the lipid source.

PMID- 15453697
TI  - Some unusual minor volatile components of tomato.
AB  - The identities and possible origins of three minor unusual volatile components of
      tomato are discussed. These are pentyl nitrate, the first identification of a
      volatile alkyl nitrate in a fresh vegetable or fruit; 5-ethyl-2(5H)-furanone,
      which, besides its presence in tomato, was found to be a major autoxidation
      product of pure (Z)-3-hexenal; and 5-ethylcyclopentene-1-carbaldehyde, a likely
      unusual linolenic acid oxidation product.

PMID- 15453698
TI  - Influence of strawberry yogurt composition on aroma release.
AB  - The primary objective of this study was to determine how yogurt ingredients
      affect aroma release in the mouth during eating. A model strawberry flavor
      consisting of ethyl butanoate, ethyl 3-methylbutanoate, (Z)-hex-3-enol, 2
      methylbutanoic acid, 5-hexylhydro-2(3H)-furanone, and 3-methyl-3-phenylglycidic
      acid ethyl ester was added to unflavored, unsweetened yogurt that had different
      added sweeteners and hydrocolloids. In all, 12 yogurt formulations were examined
      to determine the effects of gelatin, modified food starch, pectin, sucrose, high
      fructose corn syrup, and aspartame on aroma release. Aroma release was monitored
      by breath-by-breath analysis (proton-transfer reaction-mass spectrometry) during
      eating of the test yogurts. Results showed aroma release of the ethyl butanoate,
      (Z)-hex-3-enol, and ethyl 3-methylbutanoate to be suppressed by sweeteners, with
      55 DE high-fructose corn syrup having the greatest effect. Addition of thickening
      agents had no significant effect on the aroma release profiles of the compounds
      under study.

PMID- 15453699
TI  - Inverse gas chromatographic method for measurement of interactions between soy
      protein isolate and selected flavor compounds under controlled relative humidity.
AB  - An inverse gas chromatographic (IGC) method was developed to study the binding
      interactions between selected volatile flavor compounds and soy protein isolate
      (SPI) under controlled relative humidity (RH). Three volatile probes (hexane, 1
      hexanol, and hexanal) at very low levels were used to evaluate and validate
      system performance. On the basis of the thermodynamic data and the isotherms
      measured at 0% RH, 1-hexanol and hexanal had higher binding affinities than
      hexane, which could be attributed to hydrogen-bonding interactions with SPI. At
      30% RH, 1-hexanol and hexanal were retained less than at 0% RH, indicating
      possible competition for binding sites on the SPI surface between water and
      volatile probe molecules. Results showed that the thermodynamic data determined
      were comparable to the available literature values. Use of IGC allowed for the
      rapid and precise generation of sorption isotherms. Repeatability between
      replicate injections and reproducibility across columns were very good. IGC is a
      potentially high-throughput method for the sensitive, precise, and accurate
      measurement of flavor-ingredient interactions in low-moisture food systems.

PMID- 15453700
TI  - Comparative analysis of the oil and supercritical CO2 extract of Elettaria
      cardamomum (L.) Maton.
AB  - The volatile oil of Elettaria cardamomum (L.) Maton seeds was obtained by
      supercritical CO(2) extraction (SC-CO(2)). The effect of the extraction
      conditions on the yield and composition of the resulting cardamom volatile oil
      was examined by testing two pressure values, 9.0 and 11.0 MPa; two temperatures,
      40 and 50 degrees C; two flow rate values, 0.6 and 1.2 kg/h; and two particles
      size values, 250-425 and >850 microm. The extraction conditions that gave the
      highest yield, Y (grams of extract per gram of seeds), of 5.5%, were as follows:
      pressure, 9.0 MPa; temperature, 40 degrees C; carbon dioxide flow, phi = 1.2
      kg/h; and particles sizes in the range of 250-425 microm. Waxes, recovered as
      traces, were entrapped in the first separator set at 9.0 MPa and -10 degrees C.
      The oil was recovered in the second separator working at 1.5 MPa and 10 degrees
      C. The main components were as follows: alpha-terpinyl acetate, 42.3%; 1,8
      cineole, 21.4%; linalyl acetate, 8.2%; limonene, 5.6%; and linalool, 5.4%. A
      comparison with the hydrodistilled oil, obtained at a yield of 5.0%, did not
      reveal any consistent difference. In contrast, the extract obtained using hexane,
      Y = 7.6%, showed strong composition differences. Indeed, the volatile fraction of
      the extract was made up mainly of the following: limonene, 36.4%; 1,8-cineole,
      23.5%; terpinolene, 8.6%; and myrcene, 6.6%.

PMID- 15453701
TI  - Improved separation method for highly purified lutein from Chlorella powder using
      jet mill and flash column chromatography on silica gel.
AB  - We investigated an improved method for the separation of high-purified lutein
      from a commercially available spray-dried Chlorella powder (CP) using fine
      grinding by jet mill and flash column chromatography on a silica gel.
      Saponification and extraction of lutein were enhanced 2.3-2.9-fold in jet mill
      treated CP (mean particle size, 20 microm) as compared to untreated CP (mean
      particle size, 67 microm). The carotenoid extract was dissolved in ether-hexane
      (1:1 v/v) and subjected to flash column chromatography on silica gel. A mixture
      of alpha- and beta-carotene was eluted with hexane, followed by elution with
      hexane-acetone-chloroform (7:2:1 v/v). Lutein (dark-orange band) was collected
      after the elution of an unknown colorless compound (detected based on UV
      absorbance). The purity of lutein in this fraction was over 99%, and the yield
      was 60%. The present study provides key information for obtaining highly purified
      lutein using flash column chromatography on a silica gel.

PMID- 15453702
TI  - New enzymatic method for the determination of total phenolic content in tea and
      wine.
AB  - A new spectrophotometric enzymatic method for the determination of total phenol
      content in tea and wine has been developed. The method is based on the peroxidase
      catalyzed oxidation, by hydrogen peroxide, of phenols to phenoxyl radicals, which
      can react with aromatic substrates to form intensely colored adducts. In
      comparison with the widely used Folin-Ciocalteu method, this method appears to be
      more specific and more rapid and as a whole is not affected by the common
      interfering substances such as ascorbate, citrate, and sulfite. Numerous samples
      of teas and wines were analyzed by using the new method, and the results compared
      with those obtained by using the Folin and scavenging of DPPH methods. The
      differences of the total phenols content found by applying the three methods are
      discussed in terms of the different specificities of the analytical basis.

PMID- 15453703
TI  - Distribution of exogenous delta-tocopherol between the membrane lipids and
      triacylglycerols of a cod muscle-triacylglycerol model system.
AB  - Membranes of muscle foods are more susceptible to oxidation than
      triacylglycerols. Hence, directing a lipid-soluble antioxidant into the membranes
      may reduce the oxidative deterioration of muscle tissue. The objective of this
      research was to use a model system of cod muscle and triacylglycerol to study the
      distribution of exogenous delta-tocopherol between the membranes and
      triacylglycerol fractions of muscle. When ethanol was the carrier solvent, more
      tocopherol was incorporated into the membranes than when oil was the carrier.
      Addition of tocopherol to the muscle before the triacylglycerol was added allowed
      more antioxidant to be incorporated into the membranes than for the case when the
      oil was added before the antioxidant. When the triacylglycerol was solid, the
      amount of tocopherol incorporated into the membranes was higher than if the
      triacylglycerol was liquid and the amount of tocopherol incorporated into the
      membranes was less dependent on the order of tocopherol and triacylglycerol
      addition. There was a competition between the membrane lipids and triacylglycerol
      for uptake of the delta-tocopherol. In some circumstances, some of the tocopherol
      did not enter either the membrane lipid or triacylglycerol phase.

PMID- 15453704
TI  - Phytate degradation by lactic acid bacteria and yeasts during the wholemeal dough
      fermentation: a 31P NMR study.
AB  - myo-Inositol hexaphosphate (IP6) is the main source of phosphorus in cereal
      grains, and therefore, in bakery products. Different microorganisms such as
      yeasts and lactic acid bacteria have phytase enzymes able to hydrolyze IP6 during
      the wholemeal breadmaking. In this paper, the phytase activity of Lactobacillus
      plantarum, Lactobacillus brevis, Lactobacillus curvatus, and Saccharomyces
      cerevisiae strains, isolated from southern Italian sourdoughs, is assayed using
      the (31)P NMR technique. The sourdough technology based on the use of lactic acid
      bacteria in the breadmaking is finally suggested.

PMID- 15453705
TI  - Comparison of fatty acid and polar lipid contents of tubers from two potato
      species, Solanum tuberosum and Solanum phureja.
AB  - Total and individual fatty acid contents were determined in raw tubers of four
      genotypes from each of the two species Solanum phureja and S. tuberosum. The four
      S. phureja genotypes contained statistically significantly higher concentrations
      of total fatty acids, with their average value being 37% greater than that for
      the mean of the four S. tuberosum cultivars. In both species, a total of 17 fatty
      acids were detected in quantifiable amounts, and in all genotypes the predominant
      fatty acid was linoleic followed by alpha-linolenic and palmitic acids.
      Unusually, 15-methyl hexadecanoate was present as a minor acid in both species.
      Although a number of statistically significant differences in the fatty acid
      percentage compositions were found between and within the two species, these were
      generally small. Averaged over all species and genotypes, tuber storage resulted
      in an initial small but statistically significant increase in total fatty acid
      content, but prolonged storage resulted in a fall to the initial values detected
      close to harvest. The same trend was evident for S. phureja alone (for mean
      values of all genotypes), but for S. tuberosum the total fatty acid content
      remained constant over the whole storage period. For both species, the contents
      (both as absolute levels and as percent compositions) of linoleic acid decreased
      and alpha-linolenic acid increased in tubers over the whole storage period, and
      possible mechanisms are discussed. Also, the absolute levels of these two acids
      were greater in S. phureja than in S. tuberosum, and this is discussed in
      relation to the development of flavor-related compounds during cooking. The polar
      lipids of one representative of S. tuberosum and of S. phureja were qualitatively
      similar. There were only minor differences in the polar lipid percentage
      compositions and in the corresponding fatty acid compositions of the individual
      polar lipids between the two species, although the absolute levels of the total,
      and of some individual, polar lipids were higher in S. phureja.

PMID- 15453706
TI  - ACE-inhibitory activity and structural properties of peptide Asp-Lys-Ile-His-Pro
      [beta-CN f(47-51)]. Study of the peptide forms synthesized by different methods.
AB  - Some of the most potent ACE-inhibitory peptides described in food have a proline
      at the end of their sequence, a characteristic that can cause problems in the
      synthesis procedures. In this work, we studied two different preparations of
      peptide Asp-Lys-Ile-His-Pro (DKIHP), which were obtained by two different
      synthetic procedures (Boc and Fmoc). The peptide synthesized by the Boc method
      yielded a unique conformer, containing trans-Pro, and significant ACE-inhibitory
      activity (IC(50) = 113.18 microM). The chromatographic and NMR data of this
      active conformer are reported. The peptide synthesized by Fmoc chemistry yielded
      three conformers, two of them containing trans-Pro and a third one containing cis
      Pro, and showed a lower activity (IC(50) = 577.92 microM). This was attributed to
      the presence of conformers with less (or none) activity. We have pointed out the
      importance of performing structural studies on these type of peptides before
      testing their ACE-inhibitory activity.

PMID- 15453707
TI  - Elucidation of membrane destabilization in post-mortem muscles using an
      extracellular paramagnetic agent (Gd-DTPA): an NMR study.
AB  - The effect of Gd-DTPA on the development in NMR relaxation of skeletal rabbit
      muscles post-mortem was investigated by dynamic low-field (0.47 T) relaxation
      measurements from 4 min post-mortem and until 23 h post-mortem. Twelve rabbits
      were included in the study, and half of the animals were administered 0.2 mmol of
      Gd-DTPA iv 15 min before sacrifice, while the other half was administered an
      isotonic salt solution. A significant effect of Gd-DTPA treatment corresponding
      to a 25% reduction in the T(1) relaxation time was observed. T(2) relaxation was
      decomposed into two components reflecting intra- and extracellular components
      (T(2)()alpha and T(2)()beta, respectively), and Gd-DTPA treatment was found to
      affect both components. However, around 150 min post-mortem a dramatic increase
      in the difference between control and Gd-DTPA-treated rabbits was observed in the
      relaxation time of the intracellular water population (T(2)()alpha). Electrical
      stimulation of the muscles resulted in a significantly earlier onset of the
      increased effect of Gd-DTPA on the T(2)()alpha population. The increased effect
      of Gd-DTPA treatment on the T(2)()alpha component is believed to reflect leakage
      of water from the muscle cells due to membrane destabilization, known to be
      promoted by electrical stimulation. Accordingly, the present study demonstrates
      how Gd-DTPA can be used for probing membrane integrity in post-mortem muscles
      known to be of importance for subsequent water distribution and final water
      holding capacity.

PMID- 15453708
TI  - Inhibitory actions of several natural products on proliferation of rat vascular
      smooth muscle cells induced by Hsp60 from Chlamydia pneumoniae J138.
AB  - Atherosclerosis is a vascular disorder involving inflammation, a narrowed
      vascular lumen in the entire tunica intima, and reduced elasticity of the
      arterial wall. It has been found that Hsp60 from Chlamydia pneumoniae, an
      obligate bacterial pathogen associated with atheroma lesions, mimics human Hsp60,
      thereby causing attacks by immune cells on stressed endothelial cells expressing
      endogenous Hsp60 on their surface. Furthermore, Hsp60 from C. pneumoniae has been
      shown to promote the growth of vascular smooth muscle cells (VSMCs). To explore
      probes that can be used for studying signal transduction elicited by the
      chlamydial Hsp60, we have tested several natural products for their inhibitory
      actions on the Hsp60-induced proliferation of rat arterial smooth muscle cells.
      Sesamol, vanillyl alcohol, and trans-ferulic acid exhibited moderate inhibitory
      actions on the Hsp60-induced cell proliferation; zerumbone, humulene, and
      caryophylene effectively inhibited it at low concentrations with IC(50) values of
      529, 122, and 110 nM, respectively. The results indicated that the 11-membered
      alicyclic ring is favorable for interactions with receptors involved in the Hsp60
      induced VSMC proliferation.

PMID- 15453709
TI  - Induction of apoptosis by shikonin through coordinative modulation of the Bcl-2
      family, p27, and p53, release of cytochrome c, and sequential activation of
      caspases in human colorectal carcinoma cells.
AB  - Shikonin is a main constituent of the roots of Lithospermum erythrorhizon that
      has antimutagenic activity. However, its other biological activities are not well
      known. Shikonin displayed a strong inhibitory effect against human colorectal
      carcinoma COLO 205 cells and human leukemia HL-60 cells, with estimated IC(50)
      values of 3.12 and 5.5 microM, respectively, but were less effective against
      human colorectal carcinoma HT-29 cells, with an estimated IC(50) value of 14.8
      microM. Induce apoptosis was confirmed in COLO 205 cells by DNA fragmentation and
      the appearance of a sub-G1 DNA peak, which were preceded by loss of mitochondrial
      membrane potential, reactive oxygen species (ROS) generation, cytochrome c
      release, and subsequent induction of pro-caspase-9 and -3 processing. Cleavages
      of poly(ADP-ribose) polymerase (PARP) and DNA fragmentation factor (DFF-45) were
      accompanied by activation of caspase-9 and -3 triggered by shikonin in COLO 205
      cells. Here, we found that shikonin-induced apoptotic cell death was accompanied
      by upregulation of p27, p53, and Bad and down-regulation of Bcl-2 and Bcl-X(L),
      while shikonin had little effect on the levels of Bax protein. Taken together, we
      suggested that shikonin-induced apoptosis is triggered by the release of
      cytochrome c into cytosol, procaspase-9 processing, activation of caspase-3,
      degradation of PARP, and DNA fragmentation caused by the caspase-activated
      deoxyribonuclease through the digestion of DFF-45. The induction of apoptosis by
      shikonin may provide a pivotal mechanism for its cancer chemopreventive action.

PMID- 15453710
TI  - Folate content in commercial white and whole wheat sandwich breads.
AB  - After the U.S. mandate of folic acid fortification of enriched grain products, a
      report indicated higher than expected fortification. Limited information is
      available on folic acid in enriched products. We measured the folate content in
      92 sandwich breads (46 white breads and 46 whole wheat breads) in Birmingham,
      Alabama, during 2001-2003. The mean folate content in white bread declined
      significantly from 2001 to 2002 or 2003, whereas the decline in folate content in
      whole wheat bread containing enriched flour was not significant. White bread
      contained significantly more folate than whole wheat bread containing enriched
      flour in 2001 and 2003. In 2002 and 2003, >40% of breads made of enriched flour
      contained <115 microg of folate/100 g and >70% contained <160 microg/100 g. These
      percentages were markedly higher than those in 2001. Our data suggest that folic
      acid in breads containing enriched flour declined after 2001 and monitoring of
      fortification may be necessary.

PMID- 15453711
TI  - Patterns of trichothecene production, genetic variability, and virulence to wheat
      of Fusarium graminearum from smallholder farms in Nepal.
AB  - Fusarium graminearum causes wheat head blight and contaminates grain with the
      trichothecenes 4-deoxynivalenol and nivalenol. Sequence analysis of trichothecene
      genes indicates that nivalenol production is the ancestral trait; however,
      deoxynivalenol producers occur worldwide and predominate in North and South
      America and in Europe. Analysis of a large field population (>500 strains) from
      Nepal identified three groups that were both genetically distinct and polymorphic
      for trichothecene production: SCAR1 comprising 95% deoxynivalenol producers,
      SCAR2 comprising 94% nivalenol producers, and SCAR3/5 comprising 34%
      deoxynivalenol producers/63% nivalenol producers. The ability to cause wheat head
      blight differed between SCAR groups and trichothecene chemotypes: deoxynivalenol
      producers were more virulent than nivalenol producers across all three SCAR
      groups and within the SCAR3/5 genetic background. These data support the
      hypothesis that production of deoxynivalenol rather than nivalenol confers a
      selective advantage to this important wheat pathogen.

PMID- 15453712
TI  - Occurrence of ochratoxin A in cocoa products and chocolate.
AB  - In this work, the occurrence of ochratoxin A (OTA) in 170 samples of cocoa
      products of different geographical origins was studied. An immunoaffinity column
      with HPLC separation was developed to quantify low levels of OTA in cocoa bean,
      cocoa cake, cocoa mass, cocoa nib, cocoa powder, cocoa shell, cocoa butter,
      chocolate, and chocolate cream with >80% recoveries. The method was validated by
      performing replicate analyses of uncontaminated cocoa material spiked at three
      different levels of OTA (1, 2, and 5 microg/kg). The data obtained were related
      on the acceptable safe daily exposure for OTA. The highest levels of OTA were
      detected in roasted cocoa shell and cocoa cake (0.1-23.1 microg/kg) and only at
      minor levels in the other cocoa products. Twenty-six cocoa and chocolate samples
      were free from detectable OTA (<0.10 microg/kg). In roasted cocoa powder 38.7% of
      the samples analyzed contained OTA at levels ranging from 0.1 to 2 microg/kg, and
      54.8% was contaminated at >2 microg/kg (and 12 samples at >3 microg/kg).
      Ochratoxin A was detected in cocoa bean at levels from 0.1 to 3.5 microg/kg, the
      mean concentration being 0.45 microg/kg; only one sample exceeded 2 microg/kg
      (4.7%). In contrast, 51.2% of cocoa cake samples contained OTA at levels > or =2
      microg/kg, among which 16 exceeded 5 microg/kg (range of 5-9 microg/kg). These
      results indicate that roasted cocoa powder is not a major source of OTA in the
      diet.

PMID- 15453713
TI  - Hydrolysis of the amyloid prion protein and nonpathogenic meat and bone meal by
      anaerobic thermophilic prokaryotes and streptomyces subspecies.
AB  - Transmissible spongiform encephalopathies are caused by accumulation of highly
      resistant misfolded amyloid prion protein PrPres and can be initiated by
      penetration of such pathogen molecules from infected tissue to intact organism.
      Decontamination of animal meal containing amyloid prion protein is proposed
      thanks to the use of proteolytic enzymes secreted by thermophilic bacteria
      Thermoanaerobacter, Thermosipho, and Thermococcus subsp. and mesophilic soil
      bacteria Streptomyces subsp. Keratins alpha and beta, which resemble amyloid
      structures, were used as the substrates for the screening for microorganisms able
      to grow on keratins and producing efficient proteases specific for hydrolysis of
      beta-sheeted proteic structures, hence amyloids. Secretion of keratin-degrading
      proteases was evidenced by a zymogram method. Enzymes from thermophilic strains
      VC13, VC15, and S290 and Streptomyces subsp. S6 were strongly active against
      amyloid recombinant ovine prion protein and animal meal proteins. The studied
      proteases displayed broad primary specificities hydrolyzing low molecular mass
      peptide model substrates. Strong amyloidolytic activity of detected proteases was
      confirmed by experiments of hydrolysis of PrPres in SAFs produced from brain
      homogenates of mice infected with the 6PB1 BSE strain. The proteases from
      Thermoanaerobacter subsp. S290 and Streptomyces subsp. S6 are the best candidates
      for neutralization/elimination of amyloids in meat and bone meal and other
      protein-containing substances and materials.

PMID- 15453714
TI  - Univocal demonstration of the electrochemically mediated binding of Pb2+ by a
      modified surface incorporating a TTF-based redox-switchable ligand.
AB  - A tetrathiafulvalene-based redox-switchable ligand with unprecedented
      electrochemical recognition properties for a metallic cation is described and is
      chemically immobilized onto a solid surface. The recognition properties for Pb2+
      are maintained at the solid-liquid interface. Evidence of the modulation of the
      binding affinity of the modified surface, as a function of the potential applied,
      is given by EQCM analyses and by direct measurements of residual Pb2+
      concentration in solution by atomic absorption.

PMID- 15453715
TI  - Charge-reversal amphiphiles for gene delivery.
AB  - Delivering a missing gene or a functional substitute of a defective gene has the
      potential to revolutionize current medical care. Of the two gene delivery
      approaches, viral and synthetic vectors, synthetic cationic vectors possess
      several practical advantages but suffer from poor transfection efficiency. A new
      approach to gene delivery using charge-reversal amphiphiles is described. This
      synthetic vector transforms from a cationic to an anionic amphiphile
      intracellularly. This amphiphile performs two roles: first, it binds and then
      releases DNA, and second, as an anionic multicharged amphiphile, it destabilizes
      lipid bilayers. A charge-reversal amphiphile was synthesized and fully
      characterized, including the supramolecular complex it forms with DNA. Enhanced
      gene transfection was observed using these vectors compared to current cationic
      amphiphiles.

PMID- 15453716
TI  - Hydrogen bonding on the surface of poly(2-methoxyethyl acrylate).
AB  - Hydrogen bonding on the interface and in the bulk of a poly(2-methoxyethyl
      acrylate) (PMEA) thin film has been investigated by sum frequency generation,
      infrared reflection absorption, and Raman scattering measurements in different
      kinds of solutions containing hydrogen-bonding donators. These results indicate
      that the majority of the carbonyl groups on the PMEA surface are hydrogen-bonded
      with water or ethanol molecules, while the PMEA bulk is still dominated by the
      free carbonyl group.

PMID- 15453717
TI  - Multi-maleimides bearing electron-donating chromophores: reversible fluorescence
      and aggregation behavior.
AB  - A((=))-D, [A((=))](2)-D and [A ((=))](3)-D multi-maleimides and multi
      itaconimides bearing electron-donating chromophores display a strong fluorescence
      quenching due to an intramolecular charge-transfer interaction. The electron
      accepting C=C bond plays a key role in the intramolecular quenching. For the
      isomerization of these multi-itaconimides and Michael additions of these multi
      maleimides, their emission behavior is irreversible. For the Diels-Alder
      additions of these multi-maleimides, their emission behavior is reversible due to
      the reversible opening and closing of intramolecular charge-transfer pathway.
      Tris-maleimide TMPA peripherally modified with furfural alcohol displays not only
      reversible fluorescence behavior but also reversible aggregation behavior.

PMID- 15453718
TI  - Electronic substituent effects on the cleavage specificity of a non-heme Fe(2+)
      dependent beta-diketone dioxygenase and their mechanistic implications.
AB  - Acinetobacter johnsonii acetylacetone dioxygenase (Dke1) is a non-heme Fe(II)
      dependent dioxygenase that cleaves C-C bonds in various beta-dicarbonyl compounds
      capable of undergoing enolization to a cis-beta-keto enol structure. Results from
      18O labeling experiments and quantitative structure-reactivity relationship
      analysis of electronic substituent effects on the substrate cleavage specificity
      of Dke1 are used to distinguish between two principle chemical mechanisms of
      reaction: one involving a 1,2-dioxetane intermediate and another proceeding via
      Criegee rearrangement. Oxygenative cleavage of asymmetrically substituted beta
      dicarbonyl substrates occurs at the bond adjacent to the most electron-deficient
      carbonyl carbon. Replacement of the acetyl group in 1-phenyl-1,3-butanedione by a
      trifluoro-acetyl group leads to a complete reversal of cleavage frequency from
      83% to only 8% fission of the bond next to the benzoyl moiety. The structure
      activity correlation for Dke1 strongly suggests that enzymatic bond cleavage
      takes place via nucleophilic attack to generate a dioxetane, which then
      decomposes into the carboxylate and alpha-keto-aldehyde products.

PMID- 15453719
TI  - Molecular recognition in a supramolecular hydrogel to afford a semi-wet sensor
      chip.
AB  - This communication describes a new molecular recognition chip using a semi-wet
      microenvironment provided by a self-assembled hydrogel. On the basis of the
      evidence that the molecular recognition capability of artificial chemosensors are
      practically retained even in the hydrogel compared to those in aqueous solution,
      we miniaturized the functionalized hydrogel to produce an unprecedented molecular
      recognition chip. We believe that the present noncovalent immobilization method
      is generally applicable to many chemosensors, which leads to a unique semi-wet
      sensor chip suitable to convenient and high-throughput assay to plural analytes.

PMID- 15453720
TI  - Suicide inactivation of dioldehydratase by glycolaldehyde and chloroacetaldehyde:
      an examination of the reaction mechanism.
AB  - High-level ab initio calculations have been used to study the mechanism for the
      inactivation of diol dehydratase (DDH) by glycolaldehyde or 2-chloroacetaldehyde.
      As in the case of the catalytic substrates of DDH, e.g., ethane-1,2-diol, the 5'
      deoxyadenosyl radical (Ado*) is able to abstract a hydrogen atom from both
      substrate analogues in the initial step on the reaction pathway, as evidenced by
      comparable energy barriers. However, in subsequent step(s), each substrate
      analogue produces the highly stable glycolaldehyde radical. The barrier for
      hydrogen atom reabstraction by the glycolaldehyde radical is calculated to be too
      high ( approximately 110 kJ mol-1) to allow Ado* to be regenerated and recombine
      with the cob(II)alamin radical, the latter therefore remaining tightly bound to
      DDH. As a consequence, the catalytic pathway is disrupted, and DDH becomes an
      impotent enzyme. Interconversion of equivalent structures of the glycolaldehyde
      radical via the symmetrical cis-ethanesemidione radical is calculated to require
      38 kJ mol-1. EPR indications of a symmetrical cis-ethanesemidione structure are
      likely to be the result of formation of an equilibrium mixture of glycolaldehyde
      radical structures, this equilibration being facilitated by partial deprotonation
      of the glycolaldehyde radical by the carboxylate of an amino acid residue within
      the active site of DDH.

PMID- 15453721
TI  - Shape-persistent macromolecular disks from reactive supramolecular rod bundles.
AB  - We have synthesized a coil-rod-coil molecule based on a reactive rod block that
      self-organizes into a 3-D hexagonal close-packed (hcp) bundle structure in the
      melt state. Photo-cross-linking within an aromatic bundle yielded macromolecular
      disklike objects (molecular weight of 330 kDa) with a narrow size distribution
      that was essentially the same as that of the supramolecular bundles. In addition,
      cross-linking proceeded with the retention of the 3-D hcp symmetry of the
      supramolecular bundles. The 3-D symmetry of the macromolecular objects was
      observed to recover after their isolation from the solutions and transform into
      an isotropic liquid in the bulk state in a reversible way, suggesting that the
      macromolecular objects are shape-persistent in solutions as well as an isotropic
      liquid phase of the bulk.

PMID- 15453722
TI  - A generic basis for some simple light-operated mechanical molecular machines.
AB  - A novel type of mechanical switch is described in which light-induced translation
      of a macrocycle in a [2]rotaxane quenches anthracene fluorescence. Features of
      the system include the remarkable 200:1 difference in fluorescence intensity
      between the two positional states of the molecule ( approximately 85:1 between
      one isomer and the photostationary state). In principle the same concept could be
      used for mechanically switching virtually any property that can be influenced by
      functional group proximity effects.

PMID- 15453723
TI  - Rational design of an L-histidine-derived minimal artificial acylase for the
      kinetic resolution of racemic alcohols.
AB  - This communication describes the rational design of an l-histidine-derived
      minimal artificial acylase. Our new artificial acylase, tert-butyldiphenylsilyl
      ether of N-(2,4,6-triisopropylbenzenesulfonyl)-pi(Me)-l-histidinol, is a simple
      and small molecule (molecular weight = 660) that contains only one chiral carbon
      center that originates from natural l-histidine. The kinetic acylation of racemic
      secondary alcohols induced by this compound showed an S (kfast/kslow) value of up
      to 93. A reusable polystyrene-bound artificial acylase was also developed to
      examine its practical usability.

PMID- 15453724
TI  - Mediating stochastic switching of single molecules using chemical functionality.
AB  - We have studied oligo(phenylene-ethynylene)s inserted into amide-containing
      alkanethiol self-assembled monolayers using scanning tunneling microscopy to
      demonstrate switching based on chemical functionality of the environment of the
      inserted molecules. The molecules show stability in two conductance states: an ON
      and an OFF state. We demonstrate bias-dependent switching due to hydrogen bonding
      between the inserted oligo(phenylene-ethynylene) and the matrix molecules. In
      addition, the inserted molecules exhibit fewer switching events than previously
      reported for alkanethiol matrixes, which we attribute to the rigidity of the
      hydrogen-bonded matrix.

PMID- 15453725
TI  - Diastereoselective synthesis of 2,3,6-trisubstituted tetrahydropyran-4-ones via
      Prins cyclizations of enecarbamates: a formal synthesis of (+)-ratjadone A.
AB  - Enecarbamates are shown to be excellent terminating groups for Prins
      cyclizations. A noteworthy feature of this methodology is the easy,
      stereoselective construction of the cyclization precursors by alkylation of
      metalated (E)-enecarbamates with epoxides. The stereochemistry of the resultant
      trisubstituted (E)-enecarbamates is then transferred with high fidelity to afford
      the frequently observed and biologically significant all-cis-2,3,6-trisubstituted
      tetrahydropyran substructures of naturally occurring compounds. Other substituted
      tetrahydropyrans, including 2,3,5,6-tetrasubstituted, cis-2,3-disubstituted, and
      cis-2,6-disubstituted, are also accessible. This methodology facilitated an
      exceptionally concise formal total synthesis of the nuclear export inhibitor (+)
      ratjadone A.

PMID- 15453726
TI  - High efficiency of dye-sensitized solar cells based on metal-free indoline dyes.
AB  - We now report metal-free organic dyes having a new type of indoline structure,
      which exhibits high efficiencies in dye-sensitized solar cells. The solar energy
      to current conversion efficiencies with the new indoline dye was 6.51%. Under the
      same conditions, the N3 dye was 7.89% and the N719 dye was 8.26%. The new
      indoline dye was optimized for the amount of 4-tert-butyl pyridine in the
      electrolyte and cholic acid as a coadsorbent. Subsequently, the solar energy to
      current conversion efficiencies reached 8.00%. This value was the highest
      obtained efficiency for dye-sensitized solar cells based on metal-free organic
      dyes without an antireflection layer.

PMID- 15453727
TI  - Singlet vinylcarbenes: spectroscopy and photochemistry.
AB  - The first direct spectroscopic characterization of singlet vinylcarbenes is
      reported. Several vinyl amidines were converted to the corresponding
      vinylchlorodiazirines through straightforward Graham oxidation. Irradiation of
      the diazirines at 8 K in N2 matrices gave the corresponding singlet
      vinylchlorocarbenes, which could be characterized by IR, UV/vis, and
      calculational modeling. Hence, vinylchlorocarbene, 1-methylvinylchlorocarbene,
      and 1-cyclopentenylchlorocarbene were all generated and investigated. The spectra
      are consistent with localized carbene structures compared to the very delocalized
      triplet vinylcarbenes. In all cases, the carbenes readily cyclize to the
      corresponding cyclopropenes on visible irradiation, together with H-shift in the
      parent vinylchlorocarbene. In the cyclopentenyl system, cyclization leads to a
      highly strained bicyclo[3.1.0]hexene.

PMID- 15453728
TI  - A general procedure for the esterification of carboxylic acids with diazoalkanes
      generated in situ by the oxidation of N-tert-butyldimethylsilylhydrazones with
      (difluoroiodo)benzene.
AB  - The bimolecular reaction of carboxylic acids with diazoalkanes to form esters is
      among the mildest and most efficient of organic transformations but is seldom
      used in synthesis beyond the important case of methyl esterification. This is
      largely a consequence of the inaccessibility and poor stability of higher
      diazoalkanes as substrates. In this work we describe a new method for the
      synthesis of diazoalkanes by the oxidation of N-tert-butyldimethylsilylhydrazones
      (TBSHs) with (difluoroiodo)benzene, a reagent heretofore unexplored in the
      context of hydrazone oxidation. When conducted in the presence of a carboxylic
      acid substrate, the oxidation leads to efficient esterification in situ. In
      addition to greatly extending the range of diazoalkanes that are now available
      for esterifications, this new protocol offers significant advantages with regard
      to safety, for diazo intermediates are neither isolated nor achieve appreciable
      concentrations during the reaction.

PMID- 15453729
TI  - Protein encapsulation in mesoporous silicate: the effects of confinement on
      protein stability, hydration, and volumetric properties.
AB  - On the basis of the predictions of statistical-thermodynamic models, it is
      postulated that excluded volume effects may play a significant role in the
      stability, interaction, and function of proteins. We studied the effects of
      confinement on protein un/refolding and stability. Our approach was to
      encapsulate a model protein, RNase A, in a mesoporous silica, MCM-48, with
      glasslike wall structure and with well-defined pores to create a crowded
      microenvironment. To the best of our knowledge, this is the first report where
      pressure perturbation and differential scanning calorimetric techniques are
      employed to evaluate the stability, hydration, and volumetric properties of the
      confined protein. A drastic increase in protein stability ( approximately 30
      degrees C increase in unfolding temperature) is observed. The increase in
      stability is probably not only due to a restriction in conformational space
      (excluded volume effect due to nonspecific interactions) but also due to an
      increased strength of hydration of the protein within the narrow silica pores.

PMID- 15453730
TI  - 2,3-Dihydroimidazo[1,2-a]pyridines: a new class of enantioselective acyl transfer
      catalysts and their use in kinetic resolution of alcohols.
AB  - The long-known, but previously unexplored 2,3-dihydroimidazo[1,2-a]pyridine
      (DHIP) has been shown to be a competent acyl transfer catalyst. Its chiral 2
      phenyl derivatives obtainable in two steps from commercially available starting
      materials have proved to be effective acylation catalysts, giving high levels of
      enantioselectivity (s = 20-85) in kinetic resolution of secondary benzylic
      alcohols. A transition state model explaining the observed selectivity has been
      proposed.

PMID- 15453731
TI  - Group-selective ring-closing enyne metathesis: concentration-dependent
      selectivity profile of alkynylsilyloxy-tethered dienynes.
AB  - Highly group-selective ring-closing metathesis of alkynylsilyloxy-tethered
      dienynes was achieved by using Grubbs first- and second-generation catalyst. The
      remarkable selectivity increase at higher concentration for differentiating
      between two alkene moieties in nearly identical steric and stereoelectronic
      environments is believed to be the result of a higher ring-closure rate for
      smaller-sized ring formation under rapid pre-equilibration of the two alkylidene
      species generated from either alkene moiety.

PMID- 15453732
TI  - A new class of CVD precursors to metal borides: Cr(B3H8)2 and related
      octahydrotriborate complexes.
AB  - Treatment of CrCl3 with sodium octahydrotriborate, NaB3H8, affords a thermally
      unstable purple liquid thought to be a chromium(III) hydride of stoichiometry
      CrH(B3H8)2. This hydride converts rapidly at room temperature to the chromium(II)
      complex Cr(B3H8)2, which adopts a square-planar structure in which four hydrogen
      atoms form the coordination sphere of the chromium atom. This chromium(II)
      species forms six-coordinate Lewis base adducts Cr(B3H8)2L2, where L is Et2O,
      thf, or PMe3; the first two of these adopt trans geometries, whereas the latter
      is cis. Volatile Cr(B3H8)2 is the first homoleptic transition metal complex of
      the octahydrotriborate anion, and it readily forms CrB2 thin films by CVD at 250
      degrees C.

PMID- 15453733
TI  - A general bifunctional catalyst for the anti-Markovnikov hydration of terminal
      alkynes to aldehydes gives enzyme-like rate and selectivity enhancements.
AB  - A new, bifunctional catalyst for anti-Markovnikov hydration of terminal alkynes
      to aldehydes (6) allows practical room-temperature hydration of alkyl-substituted
      alkynes. Other outstanding features include near-quantitative aldehyde yields
      from both alkyl- and aryl-substituted alkynes and wide functional group
      tolerance. The uncatalyzed rate of alkyne hydration is measured for the first
      time, showing the enzyme-like rate and selectivity enhancements of aldehyde
      formation by 6. For aldehyde formation, an uncatalyzed rate <1 x 10-10 mol h-1
      means a half-life >600 000 years. The catalyzed rate is up to 23.8 mol (mol 6)-1
      h-1 and 10 000:1 ratio in favor of aldehyde. Changes in rate and selectivity
      induced by 6 are thus >2.4 x 1011 and 300 000, respectively.

PMID- 15453734
TI  - Dispersion of the third-order nonlinear optical properties of an organometallic
      dendrimer(1).
AB  - The dispersion of cubic nonlinearity in the organometallic dendrimer 1,3,5-(3,5
      {trans-[(dppe)2(4-O2NC6H4CC)RuCC]}2C6H3CCC6H4-4-CC)3C6H3 can be understood in
      terms of an interplay of two-photon absorption and absorption saturation. Simple
      dispersion relations reproduce the behavior of both the real and imaginary
      components of the hyperpolarizability.

PMID- 15453735
TI  - Catalytic asymmetric hydroxymethylation of silicon enolates using an aqueous
      solution of formaldehyde with a chiral scandium complex.
AB  - Catalytic asymmetric hydroxymethylation of silicon enolates has been achieved. In
      this reaction, an aqueous solution of formaldehyde can be used to realize an easy
      and safe procedure, and high enantioselectivities have been obtained. This is the
      first example of catalytic asymmetric reactions in aqueous media with a chiral
      scandium complex.

PMID- 15453736
TI  - A diamondoid network of tetrakis(acetamidato)dirhodium in mixed oxidation states
      linked by mu4-iodide having a 10(5) enhancement of its electrical conductivity by
      water molecules of hydration.
AB  - A mixed oxidation-state (Rh24+ and Rh25+) compound, [{Rh2(acam)4}2I]n.6nH2O
      (Hacam = acetamide), has been synthesized. The compound has a nonpenetrating
      diamondoid arrangement of {Rh2(acam)4} units linked by mu4-iodides. All of the
      dirhodium units are crystallographically equivalent, as are all of the iodide
      atoms. The magnetic susceptibility of this compound shows that one-half of the
      Rh2 units are in the Rh25+ oxidation state with one odd electron and the other
      half in the closed-shell Rh24+ state. Its electrical conductivity is 1.4 x 10-3 S
      cm-1 (pellets, room temperature) and oscillates over the range of 105 orders of
      magnitude during dehydration-rehydration cycles of interstitial water molecules.

PMID- 15453737
TI  - Highly syndiospecific polymerization of styrene catalyzed by allyl lanthanide
      complexes.
AB  - Allylic complexes of lanthanides bearing a fluorenyl-based ligand are active
      single-component catalysts for the polymerization of styrene, giving highly
      syndiotactic polymers (rrrr > 99%) with low to high molecular weight (Mn = 8000
      135 000) and narrow polydispersities (Mw/Mn = 1.25-2.1).

PMID- 15453738
TI  - A unique reaction pathway of fluorine-substituted ethyl groups on Cu(111):
      successive alpha,alpha-fluoride elimination.
AB  - Fluorine-substituted ethyl groups on Cu(111) were generated by thermal scission
      of the C-I bond in the adsorbed C2F5I. Temperature-programmed reaction
      spectrometry observed a novel pathway resulting in the evolution of C4F6 above
      400 K. Among the various isomers, this product was identified as hexafluro-2
      butyne. Although abstraction of two fluorine atoms from the starting Cu-CF2CF3
      was required, Cu-CCF3 (trifluoroethylidyne) was favored over Cu-CF=CF2
      (trifluorovinyl) as the intermediate because this ethyl-ethylidyne-butyne pathway
      was suppressed on a Cu(100) surface devoid of the key threefold hollow binding
      sites for ethylidyne. Once formed, perfluoroethylidyne readily coupled to afford
      a tightly surface-bound hexafluoro-2-butyne up to 400 K. Therefore, the C-F bonds
      adjacent to the metal were found to be more susceptible to the bond activation,
      leading the chemisorbed perfluoroethyl to eliminate two F atoms successively from
      the alpha-carbon. This preference for alpha-elimination rather than beta
      elimination (the most favorable route in hydrocarbons) may be quite general for
      metal surface-mediated reactions involving fluorinated alkyl groups.

PMID- 15453739
TI  - Unique oxidative metal-metal bond formation of linearly aligned tetranuclear Rh
      Mo-Mo-Rh clusters.
AB  - Reaction of Mo2(pyphos)4 (1) with [RhCl(CO)2]2 followed by treatment of excess
      amounts of tBuNC resulted in the clean formation of [Mo2Rh2(tBuNC)4(pyphos)4](X)2
      (4a; X = Cl). The X-ray diffraction study as well as spectroscopic analyses of 4c
      (X = BPh4) implied that there is no direct sigma-bonding interaction between each
      Rh(I) atom and the Mo2 core. Each Rh(I) atom in 4 can be oxidized concurrently by
      2 equiv of [Cp2Fe]PF6 to afford [Mo2Rh2(Cl)2(tBuNC)4(pyphos)4](PF6)2 (5) along
      with the formation of two Mo-Rh(II) single bonds and the reduction of the bond
      orders of the Mo-Mo moiety.

PMID- 15453740
TI  - Palladium-catalyzed copolymerization of ethene with acrolein dimethyl acetal:
      catalyst action and deactivation.
AB  - Acrolein dimethyl acetal (ADMA) can be copolymerized with ethene using a cationic
      alpha-diimine palladium chelate catalyst to yield branched copolymers. Catalyst
      deactivation occurs via methanol elimination to give an inert eta3-1-methoxyallyl
      palladium species. This process can be retarded by the addition of an aliquot of
      methanol to the reaction mixture, increasing overall catalyst productivity.

PMID- 15453741
TI  - Fe/Cr- and Co/Cr-mediated catalytic asymmetric 2-haloallylations of aldehydes.
AB  - The first example to couple aldehydes and 3-bromo-2-halopropenes in a catalytic
      asymmetric manner is reported. The coupling reaction is effected by the use of a
      chiral sulfonamide-Cr complex (prepared in situ from 1d, CrBr3, Fe(III) or from
      Co(II), Et3N, and Mn), TMSCl, and 2,6-lutidine. The method reported here is
      operationally simple and scalable, furnishing 3-halohomoallylic alcohols with a
      synthetically useful level of enantiomeric excess.

PMID- 15453742
TI  - Alkenes from terminal epoxides using lithium 2,2,6,6-tetramethylpiperidide and
      organolithiums or grignard reagents.
AB  - E-Alkenes (including arylated alkenes, dienes, and allylsilanes) are efficiently
      prepared by alpha-deprotonation of terminal epoxides using lithium 2,2,6,6
      tetramethylpiperidide, followed by in situ trapping with organolithiums or
      Grignard reagents.

PMID- 15453743
TI  - A highly stable short alpha-helix constrained by a main-chain hydrogen-bond
      surrogate.
AB  - Herein we describe a strategy for the preparation of artificial alpha-helices
      involving replacement of one of the main-chain hydrogen bonds with a covalent
      linkage. To mimic the C=O...H-N hydrogen bond as closely as possible, we
      envisioned a covalent bond of the type C=X-Y-N, where X and Y are two carbon
      atoms connected through an olefin metathesis reaction. Our results demonstrate
      that the replacement of a hydrogen bond between the i and i + 4 residues at the N
      terminus of a short peptide with a carbon-carbon bond results in a highly stable
      constrained alpha-helix at physiological conditions as indicated by CD and NMR
      spectroscopies. The advantage of this strategy is that it allows access to short
      alpha-helices with strict preservation of molecular recognition surfaces required
      for biomolecular interactions.

PMID- 15453744
TI  - Measuring Bronsted acid densites in zeolite HY with diphosphine molecules and
      solid state NMR spectroscopy.
AB  - The use of 31P MAS NMR spectroscopy, combined with diphenyldiphosphine
      Ph2P(CH2)nPPh2 probe molecules with two basic groups (n = 1, 3, and 6,
      corresponding to maximum P-P separations of approximately 3.0, 5.6, and 9.4 A,
      respectively), to investigate both acidities and distances between Bronsted acid
      sites in zeolite HY (Si/Al = 2.6) is demonstrated in this communication. More
      than 90% of the Ph2P(CH2)6PPh2 molecules are doubly protonated on zeolite HY at a
      loading level of 12 molecules per unit cell, indicating that there are at least
      12 pairs of Bronsted acid sites about 9 A apart. Similarly, experiments involving
      Ph2P(CH2)3PPh2 show that there are only six pairs of Bronsted acid sites
      separated by a distance of 6 A. Only approximately 60% of the Ph2PCH2PPh2
      molecules were doubly protonated for a loading level of 4 molecules/unit cell, as
      not all of the Bronsted acid sites were sufficiently acidic to protonate both
      ends of this molecule. 31P 2D double quantum NMR spectroscopy was used to confirm
      the spectral assignments.

PMID- 15453745
TI  - Membrane-bound protein in giant vesicles: induced contraction and growth.
AB  - Cell-sized giant vesicles, produced by electroformation, were composed of
      phospholipids and zein (a hydrophobic protein that occupied a substantial
      percentage of the vesicle surface). Addition of sodium dodecyl sulfate removed
      the protein into the bulk phase, which led to a shrinkage of the vesicles. The
      vesicle bilayers were able to heal themselves from the damage caused by the
      departure of the zein, allowing the bilayers to maintain their spherical
      morphology. Giant vesicle growth was also observed when the following components
      were mixed (all four being necessary): (a) negatively charged giant vesicles, (b)
      membrane-incorporated zein, (c) positively charged submicroscopic vesicles
      (almost 103 times smaller than the giant vesicles), and (d) sodium dodecyl
      sulfate. The simplest mechanism consistent with literature data involves
      electrostatically promoted binding of the small vesicles (weakened by the
      surfactant) onto the giant vesicle surface, followed by the merging of membranes
      at protein-induced "fusion hot spots". The "feeding" of small vesicles by giant
      vesicles then leads to growth.

PMID- 15453746
TI  - A diruthenium-substituted polyoxometalate as an electrocatalyst for oxygen
      generation.
AB  - Transition metal heteropolyanions have been used to catalyze a variety of organic
      oxidations but have not previously been used for O2 generation, despite sharing
      some structural similarities with dioxoruthenium water-oxidation catalysts. In
      this study, we report that the di-Ru-substituted polyoxometalate (POM)
      [Ru2Zn2(H2O)2(ZnW9O34)2]14- can be used to catalyze the electrochemical
      generation of O2. By comparing the behavior of this compound to that observed
      using a mono-Ru-substituted POM catalyst, we show that adjacent Ru sites are
      necessary to observe O2 generation. These observations suggest a reaction pathway
      involving two Ru-bound oxygen species combining to form O2 and are consistent
      with the accepted mechanism of electrochemical oxygen evolution. Finally,
      analysis of the observed electrode kinetics yields a Tafel slope of roughly 120
      mV, which is similar to values reported previously for perovskite anodes.

PMID- 15453747
TI  - Cascade reactions of substituted 1,2,4-triazines: rapid access to nitrogen
      containing polycycles.
AB  - A new and straightforward methodology for the construction of complex nitrogen
      containing polycycles has been developed. This methodology exploits easily
      prepared 1,2,4-triazines as substrates for a pericyclic reaction cascade, forming
      the polycycles in good to excellent yield in a single operation.

PMID- 15453748
TI  - Oxidative rearrangement processes in the biosynthesis of gilvocarcin V.
AB  - Gilvocarcin V (GV), an antitumor agent produced by Streptomyces griseoflavus Go
      3592 and various other streptomycetes, is the most important representative of
      the distinct family of benzo[d]naphtho[1,2-b]pyran-6-one aryl C-glycoside
      antibiotics, which show excellent antitumor activity and a remarkably low
      toxicity. The most intriguing step of its biosynthesis is an oxidative
      rearrangement cascade, in which the C-5/C-6 of an angucyclinone precursor bond is
      broken. Although this oxidative cleavage is essential for the formation of GV's
      unique chromophore and for GV's biological activity, and is likely to occur
      similarly in the biosyntheses of other angucyclinone-derived antibiotics, such as
      the kinamycins and the jadomycins, it is only poorly understood. Herein we report
      various experiments which shed light onto this intriguing oxidative cleavage
      reaction. These include incorporation studies with 18O-labeled precursors and the
      isolation and structure determination of novel intermediates of gilvocarcin
      biosynthesis accumulated by mutants, in which two genes encoding monooxygenases
      responsible for the C-C-bond cleavage of the gilvocarcin pathway, gilOI and
      gilOIV, were deleted through targeted PCR.

PMID- 15453749
TI  - Mechanism of substitution reaction on sp2-carbon center with lithium
      organocuprate.
AB  - Theory and experiments suggest that the substitution reaction of a lithium
      dialkylcuprate(I) with an alkenyl bromide takes place through a pi-complex
      (cuprio(III)cyclopropane) that directly breaks down to the alkenylated product
      rather than via a conventional three-centered transition state. This mechanism is
      consistent with the broader mechanistic picture of the organocuprate reactions
      and accounts for the retentive stereochemistry and the kinetic isotope effect
      observed in the experiments.

PMID- 15453750
TI  - Binding control and stoichiometry of ferrocenyl dendrimers at a molecular
      printboard.
AB  - Ferrocenyl-functionalized PPI dendrimers of generations 1-5 were adsorbed at self
      assembled monolayers of heptathioether-functionalized beta-cyclodextrin (betaCD)
      on gold. The dendrimers form stable supramolecular assemblies at the betaCD host
      surface having multivalent supramolecular interactions and could be
      electrochemically desorbed from the surface. Using cyclic voltammetry, the
      stoichiometries of the dendrimers at the surface could be determined for all
      generations, which were quantitatively confirmed for generations 1 and 2 by
      surface plasmon resonance titrations.

PMID- 15453751
TI  - Combining light-harvesting and charge separation in a self-assembled artificial
      photosynthetic system based on perylenediimide chromophores.
AB  - Self-assembly of robust perylenediimide chromophores is used to produce an
      artificial light-harvesting antenna structure that in turn induces self-assembly
      of a functional special pair that undergoes ultrafast, quantitative charge
      separation. The structure consists of four 1,7-(3',5'-di-tert
      butylphenoxy)perylene-3,4:9,10-perylene-3,4:9,10-bis(carboximide) (PDI) molecules
      attached to a single 1,7-bis(pyrrolidin-1-yl)perylene-3,4:9,10-perylene-3,4:9,10
      bis(carboximide) (5PDI) core, which self-assembles to form (5PDI-PDI4)2 in
      toluene. The system is characterized using both structural methods (NMR, SAXS,
      mass spectroscopy, and GPC) and photophysical methods (UV-vis, time-resolved
      fluorescence, and femtosecond transient absorption spectroscopy). Energy transfer
      from (PDI)2 to (5PDI)2 occurs with tau = 21 ps, followed by excited-state
      symmetry breaking of 1*(5PDI)2 to produce 5PDI*+-5PDI*- quantitatively with tau =
      7 ps. The ion pair recombines with tau = 420 ps. Electron transfer occurs only in
      the dimeric system and does not occur in the disassembled monomer, thus mimicking
      both antenna and special pair function in photosynthesis.

PMID- 15453753
TI  - Fluoride-facilitated deuterium exchange from DMSO-d6 to polyamide-based
      cryptands.
AB  - Multiple deuterium exchange between DMSO-d6 and amide hydrogens in two hexaamido
      cryptand fluoride receptors has been verified by 19F and 2H NMR and FAB mass
      spectral studies. Structural results for one of the complexes indicate a
      tricapped trigonal prism hydrogen bond coordination geometry around an
      encapsulated fluoride, with hydrogen bonds from fluoride to six amide and three
      phenyl hydrogens.

PMID- 15453752
TI  - Ultrasensitive electrocatalytic DNA detection at two- and three-dimensional
      nanoelectrodes.
AB  - Electrochemical DNA detection systems are an attractive approach to the
      development of multiplexed, high-throughput DNA analysis systems for clinical and
      research applications. We have engineered a new class of nanoelectrode ensembles
      (NEEs) that constitute a useful platform for biomolecular electrochemical
      sensing. High-sensitivity DNA detection was achieved at oligonucleotide
      functionalized NEEs using a label-free electrocatalytic assay. Attomole levels of
      DNA were detected using the NEEs, validating the promise of nanoarchitectures for
      ultrasensitive biosensing.

PMID- 15453754
TI  - In situ cryocrystallization of diphenyl ether: C-H...pi mediated polymorphic
      forms.
AB  - Polymorphism in diphenyl ether has been identified during in situ crystallization
      via single-crystal X-ray diffraction. Only weak inter- and intramolecular C
      H...pi interactions control the packing of the molecules in both crystal forms
      monoclinic centrosymmetric (P21/n) in form I and orthorhombic noncentrosymmetric
      (P212121) in form II.

PMID- 15453755
TI  - Self-assembly of phospholipid molecules at a Au(111) electrode surface.
AB  - We described the first scanning tunneling microscopy study of spreading
      unilamellar vesicles of 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine (DMPC)
      at a Au(111) electrode surface. At the initial stage of the film formation, the
      molecular resolution images revealed that DMPC molecules are adsorbed flat with
      the acyl chains oriented parallel to the surface. The molecules assemble into
      double rows by aligning the acyl chains in the nearest neighbor direction of the
      reconstructed Au(111) surface and assuming a 90 +/- 10 degrees angle with respect
      to line of the molecular row. After approximately 30 min, this film is
      transformed into a hemimicellar state with long rows characteristic for the
      formation of hemicylindrical surface micelles. At hydrophilic surfaces such as
      glass, spreading of vesicles involves adsorption, rupture, and sliding of a
      single bilayer on a lubricating film of the solvent. We have provided the first
      evidence that a different mechanism is involved in spreading the vesicles at
      gold. The molecules released by rupture of vesicles self-assemble into an ordered
      film, and the assembly is controlled by the chain-substrate interaction.

PMID- 15453756
TI  - Alpha-helical peptides are not protonated at the N-terminus in the gas phase.
AB  - DFT/AM1 ONIOM calculations using B3LY/D95** indicate that protonations of alpha
      helical alaN (N = 14, 17) occur preferentially at the COOH and C=O groups near
      the COOH terminus of the peptides. Protonations at the N-termini lead to local
      helical unraveling. The preference for protonation at or near the COOH terminus
      increases with N. Hydration should relatively favor the N-protonated structures,
      but at the expense of further unraveling. Since alpha-helices in proteins often
      form "bundles" that are not well-hydrated, the C=O groups at the ends of these
      helices might be readily protonated.

PMID- 15453757
TI  - Biscopper complexes of meso-aryl-substituted hexaphyrin: gable structures and
      varying antiferromagnetic coupling.
AB  - The copper metalation into the hexaphyrins is accompanied by large structural
      changes to give four complexes exhibiting gable structures and varying
      antiferromagnetic couplings.

PMID- 15453758
TI  - Control of viscoelasticity using redox reaction.
AB  - The viscoelasticity of a fluid was tuned with the Faradaic reaction of (11
      ferrocenylundecyl)trimethylammonium bromide (FTMA), a "redox-switchable"
      surfactant. An aqueous solution of the reduced form of FTMA exhibited a
      remarkable viscoelasticity in the presence of sodium salicylate (NaSal) because
      of the formation of three-dimensional entanglement of wormlike micelles.
      Electrolytic oxidation of FTMA caused the viscosity of the system to dramatically
      decrease and the elasticity to disappear. This drastic decrease in
      viscoelasticity arose from the disruption of wormlike micelles. This novel
      electrorheological phenomenon is expected to be applicable to ink for inkjet
      printers, the electrochemically controlled release of substances entrapped in
      wormlike micelles of FTMA, and fluid flow rate control using electric signals.

PMID- 15453759
TI  - Tapping mode AFM evidence for an amorphous reticular phase in a condensation
      cured hybrid elastomer: alpha,omega
      dihydroxypoly(dimethylsiloxane)/poly(diethoxysiloxane)/fumed silica
      nanoparticles.
AB  - A new surface phenomenon is reported for hybrid nanocomposites comprising (1) a
      low Tg poly(dimethylsiloxane) (PDMS) phase cross-linked by (2) a siliceous phase
      (SP) generated by in situ hydrolysis/condensation of poly(diethoxysiloxane)
      (PDES), and (3) fumed silica nanoparticles (FSN). After ambient temperature cure,
      tapping mode atomic force microscopy (TM-AFM) easily reveals near-surface FSN.
      For nanocomposites with higher PDES content, FSN surprisingly "disappear" after a
      further cure at 100 degrees C. The observation is explained by further
      condensation of extant siliceous fragments creating an amorphous reticular phase,
      which acts as a mechanical barrier between the FSN and the AFM tip.

PMID- 15453760
TI  - Reorganization and growth of metastable alpha-N2 critical nuclei into stable beta
      N2 crystals.
AB  - We report on results on the crystal nucleation and growth of nitrogen. Using
      molecular dynamics simulations, we show that while nucleation proceeds into the
      metastable alpha-phase (i.e., the crystalline phase associated with the lowest
      free energy barrier of formation), growth of the crystallite proceeds through a
      reorganization of the nucleus into the thermodynamically stable beta-phase.

PMID- 15453761
TI  - Efficient enantioselective synthesis of functionalized tetrahydropyrans by Ru
      catalyzed asymmetric ring-opening metathesis/cross-metathesis (AROM/CM).
AB  - An efficient method for enantioselective synthesis of highly functionalized
      pyrans (up to 98% ee) through Ru-catalyzed asymmetric ring-opening
      metathesis/cross-metathesis is described. Reactions are promoted by a recyclable
      chiral Ru-chloride or a new chiral Ru-iodide complex; the latter catalyst is less
      efficient but gives rise to significantly higher levels of enantioselectivity.
      Catalytic reactions can be performed in undistilled solvent and with a wide range
      of substrates, including those that contain secondary and tertiary alcohols.
      Representative regioselective functionalizations that highlight the utility of
      the catalytic method are also presented.

PMID- 15453762
TI  - Analysis of the conserved P9-G10.1 metal-binding motif in hammerhead ribozymes
      with an extra nucleotide inserted between A9 and G10.1 residues.
AB  - Hammerhead ribozymes (Rz) have catalytically important tandem G:A pairs in the
      core region, and we recently demonstrated that the P9-G10.1 motif (a sheared-type
      G:A pair with a guanine residue on the 3' side of the adenine residue) with
      several flanking base pairs is sufficient for capture of divalent cations, such
      as Mg(2+) and Cd(2+) ions that are important to maintain full activities (Tanaka
      et al. J. Am. Chem. Soc. 2002, 124, 4595-4601; Tanaka et al. J. Am. Chem. Soc.
      2004, 126, 744-752). We also found that mutant hammerhead ribozymes that have an
      additional G residue inserted between A9 and G10.1 residues (the metal-binding P9
      G10.1 motif) have significant catalytic activities. In this study, we demonstrate
      that the hammerhead ribozymes are capable of maintaining the catalytically
      competent structure even when the tandem, sheared-type G:A pairs were perturbed
      by an insertion of an additional nucleotide, whereas the chirality of the
      phosphorothioate at the P9 position significantly influenced the enzymatic
      activity for both the natural and G-inserted ribozymes.

PMID- 15453763
TI  - Accelerated color change of gold nanoparticles assembled by DNAzymes for simple
      and fast colorimetric Pb2+ detection.
AB  - The combination of high metal selectivity of DNAzymes with the strong distance
      dependent optical properties of metallic nanoparticles has presented considerable
      opportunities for designing colorimetric sensors for metal ions. We previously
      communicated a design for a colorimetric lead sensor based on the assembly of
      gold nanoparticles by a Pb(2+)-dependent DNAzyme. However, heating to 50 degrees
      C followed by a cooling process of approximately 2 h was required to observe the
      color change. Herein we report a new improved design that allows fast (<10 min)
      detection of Pb(2+) at ambient temperature. This improvement of sensor
      performance is a result of detailed studies of the DNAzyme and nanoparticles,
      which identified "tail-to-tail" nanoparticle alignment, and large (42 nm
      diameter) nanoparticle size as the major determining factors in allowing fast
      color changes. The optimal conditions for other factors such as temperature (35
      degrees C) and concentrations of the DNAzyme (2 microM), its substrate (3 nM),
      and NaCl (300 mM) have also been determined. These results demonstrate that
      fundamental understanding of the DNAzyme biochemistry and nanoparticle science
      can lead to dramatically improved colorimetric sensors.

PMID- 15453764
TI  - Chemoenzymatic synthesis and high-throughput screening of an aminoglycoside
      polyamine library: identification of high-affinity displacers and DNA-binding
      ligands.
AB  - Chemoenzymatic parallel synthesis and high-throughput screening were employed to
      develop a multivalent aminoglycoside-polyamine library for use as high-affinity
      cation-exchange displacers and DNA-binding ligands. Regioselective lipase
      catalyzed acylation, followed by chemical aminolysis, was used to generate vinyl
      carbonate and vinyl carbamate linkers, respectively, of the aminoglycosidic
      cores. These were further derivatized with polyamines, leading to library
      generation. A parallel batch-displacement assay was employed to identify the
      efficacy of the library candidates as potential displacers for protein
      purification. Using this approach, low-molecular-mass displacers with affinities
      higher than those previously observed have been identified. The aminoglycoside
      polyamine library was also screened for DNA binding efficacy using an ethidium
      bromide displacement assay. These highly cationic molecules exhibited strong DNA
      binding properties and may have potential for enhanced gene delivery.

PMID- 15453765
TI  - Magnetic circular dichroism and cobalt(II) binding equilibrium studies of
      Escherichia coli methionyl aminopeptidase.
AB  - Equilibrium dialysis of methionyl aminopeptidase from Escherichia coli (EcMetAP)
      monitored by atomic absorption spectrometry and magnetic circular dichroism (MCD)
      shows that the enzyme binds up to 1.1 +/- 0.1 equiv of Co(2+) in the metal
      concentration range likely to be found in vivo. The dissociation constant, K(d),
      is estimated to be between 2.5 and 4.0 microM. Analysis of the temperature and
      magnetization behavior of the two major peaks in the MCD spectrum at 495 and 567
      nm suggests that these transitions arise from Co(2+) with different ground
      states. Ligand field calculations using AOMX are used to assign the 495 nm peak
      to Co(2+) in the 6-coordinate binding site and the 567 nm peak to Co(2+) in the 5
      coordinate site. This is further supported by the fact that the binding affinity
      of the Co(2+) associated with the 567 nm peak is enhanced when the pH is
      increased from 7.5 to 9.0, consistent with having an imidazole ligand from a
      histidine amino acid residue. On the basis of the MCD intensities, it is
      estimated that, when the 5-coordinate site is fully occupied, 0.1 equiv of cobalt
      is in the 6-coordinate site. Even when the cobalt concentration is very low,
      there is a small fraction of binuclear sites in EcMetAP formed through
      cooperative binding between the 5- and 6-coordinate Co(2+) ions. The
      magnetization behavior of the 6-coordinate Co(2+) MCD peak is consistent with an
      isolated pseudo-Kramer doublet ground state, suggesting that the cobalt ions in
      the binuclear sites are not magnetically coupled.

PMID- 15453766
TI  - Substituent-dependent photoinduced intramolecular charge transfer in N-aryl
      substituted trans-4-aminostilbenes.
AB  - The photochemical behavior of trans-4-(N-arylamino)stilbene (1, aryl = 4
      substituted phenyl) in solvents more polar than THF is strongly dependent on the
      substituent in the N-aryl group. This is attributed to the formation of a twisted
      intramolecular charge transfer (TICT) state for those with a methoxy (1OM),
      methoxycarbonyl (1CO), or cyano (1CN) substituent but not for those with a methyl
      (1Me), hydrogen (1H), chloro (1Cl), or trifluoromethyl (1CF) substituent. On the
      basis of the ring-bridged model compounds 3-6, the TICT states for 1CN and 1CO
      result from the twisting of the anilino-benzonitrilo C-N bond, but for 1OM it is
      from the twisting of the stilbenyl-anilino C-N bond, both of which are distinct
      from the TICT states previously proposed for N,N-dimethylaminostilbenes.

PMID- 15453767
TI  - Ultrathin polymer film formation by collision-induced cross-linking of adsorbed
      organic molecules with hyperthermal protons.
AB  - A new synthetic approach for the formation of ultrathin polymer films with
      customizable properties was developed. In this approach, the kinematic nature of
      proton collisions with simple organic molecules condensed on a substrate is
      exploited to break C-H bonds preferentially. The subsequent recombination of
      carbon radicals gives a cross-linked polymer thin film, and the selectivity of C
      H cleavage preserves the chemical functionalities of the precursor molecules. The
      nature and validity of the method are exemplified with theoretical results from
      ab initio molecular dynamics calculations and experimental evidence from a
      variety of characterization techniques. Its applicability is demonstrated by the
      synthesis of ultrathin polymer films with precursor molecules such as
      dotriacontane, docosanoic acid, poly(acrylic acid) oligomer, and polyisoprene.
      The approach is fundamentally different from conventional chemical synthesis as
      it involves an unusual mix of physical and chemical processes including charge
      exchange, projectile penetration, kinematics, collision-induced dissociation,
      inelastic energy transfer, chain transfer, and chain cross-linking.

PMID- 15453768
TI  - Thiyl radical-mediated cleavage of allylic C-N bonds: scope, limitations, and
      theoretical support to the mechanism.
AB  - Thiols mediate the radical isomerization of allylic amines into enamines. The
      reaction results in the cleavage of the allylic C-N bond, after treatment with
      aqueous HCl. The mechanism involves the abstraction of an allylic hydrogen alpha
      to nitrogen by thiyl radical, followed by a return hydrogen transfer from the
      thiol to the carbon gamma to nitrogen in the intermediate allylic radical. The
      scope and limitations of the reaction with respect to the nature of the thiol, to
      the structure of the allylic chain, and to the nature of the substituents at
      nitrogen were investigated. The experimental results were interpreted on the
      ground of DFT calculations of the C-Halpha BDE in the starting allylic amines,
      and of the C-Hgamma BDE in the resulting enamines. The efficiency of the initial
      hydrogen transfer is the first requirement for the reaction to proceed. A balance
      must be found between the S-H BDE and the two above-mentioned C-H BDEs. The
      incidence of stereoelectronic factors was analyzed through NBO calculations
      performed on the optimized geometries of the starting allylic amines. Additional
      calculations of the transition structures and subsequent tracing of the reaction
      profiles were performed for the abstraction of Halpha from both the allyl and the
      prenyl derivatives by p-TolS(*). The latter allowed us to estimate the rate
      constant for the abstraction of hydrogen by thiyl radical from an N-prenylamine
      and an N-allylamine.

PMID- 15453769
TI  - Fate of diradicals in the caldera: stereochemistry of thermal stereomutation and
      ring enlargement in cis- and trans-1-cyano-2(E)-propenylcyclopropanes.
AB  - This study of thermally induced stereomutation and ring enlargement in both (-)
      trans-1-cyano-2(E)-propenylcyclopropane [(-)-trans-1] and (+)-cis-1-cyano-2(E)
      propenylcyclopropane [(+)-cis-1] to cyclopentenes definitively contraindicates
      the usefulness of Woodward-Hoffmann rules of orbital symmetry as a theoretical
      basis for predicting the stereochemistry of the products. From both
      diastereomers, the same (+)-trans-4-cyano-3-methylcyclopentene [(+)-trans-2] is
      the major product among the four diastereomeric products, "allowed" and formally
      the result of a single internal rotation of the cyano-bearing carbon atom from (
      )-trans-1, "forbidden" and the result of zero internal rotations from (+)-cis-1.
      Stereomutation and ring enlargement are discussed in detail in terms of
      rotational propensity, thermodynamic preference, and the possible role of
      diradicals in transit and diradicals as intermediates in a caldera.

PMID- 15453770
TI  - Cycloalkene ozonolysis: collisionally mediated mechanistic branching.
AB  - Master equation calculations on a computational potential energy surface reveal
      that collisional stabilization at atmospheric pressure becomes important in the
      gas-phase ozonolysis of endocyclic alkenes for a carbon number between 8 and 15.
      Because the reaction products from endocyclic ozonolysis are tethered, this
      system is ideal for consideration of collisional energy transfer, as chemical
      activation is confined to a single reaction product. Collisional stabilization of
      the Criegee intermediate precedes collisional stabilization of the primary
      ozonide by roughly an order of magnitude in pressure. The stabilization of the
      Criegee intermediate leads to a dramatic transformation in the dominant oxidation
      pathway from a radical-forming process at low carbon number to a secondary
      ozonide-forming process at high carbon number. Secondary ozonide formation is
      important even for syn-isomer Criegee intermediates, contrary to previous
      speculation. We use substituted cyclohexenes as analogues for atmospherically
      important mono- and sesquiterpenes, which are major precursors for secondary
      organic aerosol formation in the atmosphere. Combining these calculations with
      literature experimental data, we conclude that the transformation from chemically
      activated to collisionally stabilized behavior most probably occurs between the
      mono- and sesquiterpenes, thus causing dramatically different atmospheric
      behavior.

PMID- 15453771
TI  - Conformational effects on glycoside reactivity: study of the high reactive
      conformer of glucose.
AB  - The effect of conformation on glycoside reactivity was investigated by studying
      the hydrolysis of a selection of 3,6-anhydroglucosides as models for glucose in
      the highly reactive (1)C(4) conformation. Methyl 3,6-anhydro-beta-D
      glucopyranoside was found to hydrolyze 200-400 times faster than methyl
      glucosides in the (4)C(1) conformation, while methyl 3,6-anhydro-beta-D
      galactopyranoside, which is in the B(1,4) conformation, was less reactive than
      methyl beta-D-galactopyranoside. Methyl (3,6-anhydro-beta-D-glucopyranosyl)-(1 -
      > 6)-alpha-D-glucopyranoside, methyl (3,6-anhydro-alpha-D-glucopyranosyl)-(1 -->
      6)-alpha-D-glucopyranosyl-(1 --> 6)-alpha-D-glucopyranoside, and methyl (3,6
      anhydro-beta-D-glucopyranosyl)-(1 --> 6)-alpha-D-glucopyranosyl-(1 --> 6)-alpha-D
      glucopyranoside were prepared and found to react selectively at the anhydro
      residue. The finding that (1)C(4) conformers of glucosides are highly reactive
      species is in accordance with and supports previous results showing that axial OH
      groups are less electron withdrawing than equatorial OH groups.

PMID- 15453772
TI  - Hydrogen bonded oligohydrazide foldamers and their recognition for saccharides.
AB  - This paper describes the synthesis and characterization of the first series of
      hydrogen bonding-driven hydrazide foldamers and their recognition for alkyl
      saccharides in chloroform. Oligomers 1, 2-4, 5, 6, and 7, which contain one, two,
      four, six, or twelve repeated dibenzoyl hydrazide residues, respectively, have
      been prepared. The rigid and planar conformations of 1 and 2 or 4 have been
      established with X-ray analysis and (1)H NMR spectroscopy, whereas the folding
      and helical conformations of 5-7 have been evidenced by the 1D and 2D (1)H NMR
      and IR spectroscopy and molecular mechanics calculations. Molecular mechanics
      calculations also revealed that 5, 6, and 7 possess a rigid cavity with size of
      ca. 10.6 to 11.1 A, and half of the carbonyl groups in the folding conformations
      are orientated inwardly inside the cavity. (1)H NMR and CD experiments revealed
      that 5-7 efficiently complex alkylated mono- and disaccharides 32-35 in
      chloroform. The association constants (K(assoc)) of the complexes have been
      determined with the (1)H NMR and fluorescent titration methods. The energy
      minimized conformation of 6.34 has been obtained with molecular mechanics
      calculation. The hydrazide-based folding structures described here represent
      novel examples of hydrogen bonding-driven foldamers that act as artificial
      receptors for selective molecular recognition.

PMID- 15453773
TI  - A highly efficient, preorganized macrobicyclic receptor for halides based on
      CH... and NH...anion interactions.
AB  - The preorganized, macrobicyclic azaphane (1) exhibits remarkable strong,
      selective fluoride binding comparable to the most effective bis(tren) cryptands
      despite binding anions via only three NH groups coupled with three CH hydrogen
      bond donors. The lower intrinsic affinity of CH donors is compensated by the high
      degree of preorganization exhibited by azacyclophane 1. Compound 1 is prepared
      via a tripod-tripod cyclization reaction between 1,3,5-tris-bromomethyl-benzene
      and an aliphatic tripodal hexatosylated polyamine, followed by the reduction of
      the resulting bicyclic tosylamine. The crystal structures of the bicyclic
      tosylamine 2 and four macrobicyclic polyammonium halide salts of 1 are reported.
      X-ray studies revealed the formation of inclusive 1:1 complexes of 1 with
      fluoride, chloride, bromide, and iodide. Potentiometric titrations showed very
      high binding constants for fluoride and chloride with a F(-)/Cl(-) selectivity of
      more than five logarithmic units. The final geometry of the anion cryptates is
      largely determined by optimization of NH and CH...anion interactions coupled with
      unfavorable anion-pi repulsion for the larger anions.

PMID- 15453774
TI  - Tuning organogels and mesophases with phenanthroline ligands and their copper
      complexes by inter- to intramolecular hydrogen bonds.
AB  - A novel family of highly functionalized molecules consisting of a central 4
      methyl-3,5-diacylaminobenzene platform linked in close proximity to the methyl
      group by two lateral aromatic rings each equipped with two long alkoxy chains has
      been rationally designed. The presence of amide tethers and a chelating
      phenanthroline fragment connected via an ester dipole formed a new class of
      gelating reagents and mesomorphic materials. A few of these compounds have the
      tendency to form macromolecule-like aggregates through noncovalent interactions
      in hydrocarbon solvents and were found to exhibit thermotropic cubic mesophases.
      In light of the X-ray molecular structure of the methoxy ligand, an infinite
      network maintained by intermolecular hydrogen bonds as well as by pi-pi stacking
      of the phenyl subunits was evidenced. FT-IR studies confirm that the common
      driving force for aggregation in the organogels and microsegregation in the
      mesophase is the occurrence of a tight intermolecular H-bonded network that does
      not persist in diluted solution. This situation is switched when the ligands are
      interlocked by a copper(I) cation. A strong intramolecular H-bond confirmed by X
      ray diffraction of a single crystal for the methoxy case provides very stable
      complexes but inhibits the gelation of the solvents. Heating the complexes
      bearing long paraffin chains (n = 12 and 16) in the dried state leads to a self
      organization into a columnar liquid-crystalline phase in which the columns are
      arranged along a 2D oblique symmetry as deduced from powder XRD experiments. In
      this case, the complexes with the appended counteranions self-assemble in a
      specific way to form columns. A striking observation is that the intramolecular
      hydrogen bond persists in the mesophase as it does in solution without any
      evidence of an extended network. As far as we are aware, these ligands and
      complexes are rare examples in which organogelation and thermotropic mesomorphic
      behavior could be observed in parallel with molecules bearing a chelating
      platform. Due to the synthetic availability of the 4-methyl-3,5
      diacylaminobenzene core and the simplicity by which the chelating platforms can
      be graphed, this methodology represents a practical alternative to the production
      of functionalized organogelators and mesomorphic materials.

PMID- 15453775
TI  - Amine attack on coordinated alkenes: an interconversion from anti-Markovnikoff to
      Markovnikoff products.
AB  - A sequence of alkene complexes of platinum, PtCl(2)(PPh(3))(alkene) (alkene =
      ethylene, propene, 1-butene, cis-2-butene, 1-hexene, 1-octene, and 1-decene), has
      been prepared. These complexes are characterized by NMR spectroscopy, including
      assignment of each proton, and X-ray crystal structures of the 1-propene and 1
      hexene complexes. Each complex was reacted with diethylamine. For the 1-hexene, 1
      octene, and 1-decene complexes, the amine displaces the alkene. For the smaller
      alkenes, the diethylamine nucleophilically attacks the coordinated alkene. For
      propene and 1-butene, the low-temperature addition leads to the anti-Markovnikoff
      nucleophilic attack, which slowly converts at room temperature to the
      Markovnikoff product. The transformation from anti-Markovnikoff to Markovnikoff
      addition occurs without diethylamine dissociation.

PMID- 15453776
TI  - Solvent-equilibrated ion pairs from carbene fragmentation reactions.
AB  - [R(+) OC Cl(-)] ion pairs were generated in methanol/dichloroethane solutions,
      with R(+) as the 1-bicyclo[2.2.2]octyl, 1-adamantyl, or 3-homoadamantyl cation.
      Ion pairs were produced either by the direct fragmentation of
      alkoxychlorocarbenes (ROCCl), with R = 1-bicyclo[2.2.2]octyl, 1-adamantyl, or 3
      homoadamantyl, or by the ring expansion-fragmentation of R'CH(2)OCCl, with R' = 1
      norbornyl, 3-noradamantyl, or 1-adamantyl. Correlations of the [ROMe]/[RCl]
      product ratios as a function of the mole fraction of MeOH in dichloroethane
      showed that the homoadamantyl chloride ion pairs, produced by either the direct
      or ring expansion-fragmentations, were identical, solvent- and anion
      equilibrated, and precursor independent. Laser flash photolysis experiments gave
      20-30 ps as the time required for solvent equilibration and precursor
      independence. Methanol/chloride selectivities of the (less-stable) 1-adamantyl
      chloride and 1-bicyclo[2.2.2]octyl chloride ion pairs were not independent of
      their ROCCl or R'CH(2)OCCl precursors. Computational studies provided transition
      states for the fragmentations and for the structures of the ion pairs.

PMID- 15453777
TI  - Total synthesis of (+)-brasilenyne. Application of an intramolecular silicon
      assisted cross-coupling reaction.
AB  - The first enantioselective total synthesis of (+)-brasilenyne (1) has been
      achieved in 19 linear steps, with 5.1% overall yield from l-(S)-malic acid. The
      construction of the oxonin core containing a 1,3-cis,cis diene unit was
      accomplished with a tandem ring-closing metathesis/silicon-assisted
      intramolecular cross-coupling reaction. In addition, a key propargylic
      stereogenic center was created through a novel, highly diastereoselective ring
      opening of a 1,3-dioxolanone promoted by TiCl(4). This reaction proceeded through
      an oxocarbenium ion intermediate and the asymmetric induction was fully
      controlled by l-malic acid residue. The C(8) stereogenic center was set by a
      reagent-controlled asymmetric allylboration.

PMID- 15453778
TI  - Electrochemically controlled chemically reversible transformation of alpha
      tocopherol (vitamin E) into its phenoxonium cation.
AB  - Alpha-tocopherol (alpha-TOH) can be electrochemically oxidized in CH(3)CN
      containing Bu(4)NPF(6) in a chemically reversible two-electron/one-proton (ECE)
      process to form the phenoxonium cation (alpha-TO(+)) that is stable for at least
      several hours at 243 K. In the presence of up to approximately 1% CF(3)SO(3)H,
      alpha-TO(+) exists in equilibrium with the alpha-tocopherol cation radical (alpha
      TOH(+)(*)), whereas at concentrations between approximately 1-3% CF(3)SO(3)H the
      electrochemical oxidation of alpha-TOH occurs by close to one-electron to form
      alpha-TOH(+)(*).alpha-TOH(+)(*) can be further oxidized in a one-electron process
      to form the alpha-tocopherol dication (alpha-TOH(2+)). The identity and stability
      of the phenolic cationic compounds were determined by a combination of
      electrochemical (cyclic voltammetry and controlled potential electrolysis) and in
      situ spectroscopic (UV-vis-NIR, FTIR, EPR, and NMR) analysis.

PMID- 15453779
TI  - Alkylating agents stronger than alkyl triflates.
AB  - A new class of potent electrophilic "R(+)" alkylating agents has been developed
      using weakly nucleophilic carborane anions as leaving groups. These reagents,
      R(CHB(11)Me(5)X(6)) (R = Me, Et, and i-Pr; X = Cl, Br), are prepared via
      metathesis reactions with conventional alkylating agents such as alkyl triflates,
      using the high oxophilicity of silylium ion-like species, Et(3)Si(carborane), as
      the driving force to obtain increased alkyl electrophilicity. The crystal
      structure of the isopropyl reagent, i-Pr(CHB(11)Me(5)Br(6)), has been determined,
      revealing covalence in the alkyl-carborane bonding. This contrasts with the free
      i-Pr(+) carbocation observed when the anion is less coordinating (e.g.
      Sb(2)F(11)(-)) or with tertiary alkyl centers, as in [tert-butyl][carborane]
      salts. In solution, the reagents exist as equilibrating isomers with the alkyl
      group at the 7-11 or 12 halide positions of the CB(11) icosahedral carborane
      anion. These alkylating agents are so electrophilic that they (a) react with
      alkanes at or below room temperature via hydride extraction to produce carbenium
      ions, (b) alkylate benzene without a Friedel-Crafts catalyst to give arenium
      ions, and (c) alkylate electron-deficient phosphorus compounds that are otherwise
      inert to conventional alkylating agents such as methyl triflate.

PMID- 15453780
TI  - Synthesis of alkylated deoxynojirimycin and 1,5-dideoxy-1,5-iminoxylitol
      analogues: polar side-chain modification, sulfonium and selenonium heteroatom
      variants, conformational analysis, and evaluation as glycosidase inhibitors.
AB  - The syntheses of N-alkylated deoxynojirimycin and 1,5-dideoxy-1,5-iminoxylitol
      derivatives having either a D- or an L-erythritol-3-sulfate functionalized N
      substituent are reported. The alkylating agent used was a cyclic sulfate
      derivative, whereby selective attack of the nitrogen atom at the least hindered
      primary center afforded the desired ammonium salt. In aqueous solution, these
      salts were configurationally labile at the ammonium center. Sulfonium and/or
      selenonium analogues of the ammonium salts were prepared by analogous reactions.
      The chalcogen salts were obtained as mixtures of diastereomers, separable in some
      cases, differing only in the stereochemistry at the configurationally stable
      sulfur or selenium atoms. Proof of configuration and conformation of each
      compound was obtained by detailed NMR experiments. The compounds are six-membered
      ring analogues of salacinol, a known sulfonium-salt glucosidase inhibitor.
      Evaluation of the target compounds for enzyme inhibition of the glucosidase
      enzyme glucoamylase G2 indicated that these compounds were either inactive or, at
      best, only weak inhibitors of maltose hydrolysis.

PMID- 15453781
TI  - Development of a zinc ion-selective luminescent lanthanide chemosensor for
      biological applications.
AB  - Detection of chelatable zinc (Zn(2+)) in biological studies has attracted much
      attention recently, because chelatable Zn(2+) plays important roles in many
      biological systems. Lanthanide complexes (Eu(3+), Tb(3+), etc.) have excellent
      spectroscopic properties for biological applications, such as long luminescence
      lifetimes of the order of milliseconds, a large Stoke's shift of >200 nm, and
      high water solubility. Herein, we present the design and synthesis of a novel
      lanthanide sensor molecule, [Eu-7], for detecting Zn(2+). This europium (Eu(3+))
      complex employs a quinolyl ligand as both a chromophore and an acceptor for
      Zn(2+). Upon addition of Zn(2+) to a solution of [Eu-7], the luminescence of
      Eu(3+) is strongly enhanced, with high selectivity for Zn(2+) over other
      biologically relevant metal cations. One of the important advantages of [Eu-7] is
      that this complex can be excited with longer excitation wavelengths (around 340
      nm) as compared with previously reported Zn(2+)-sensitive luminescent lamthanide
      sensors, whose excitation wavelength is at too high an energy level for
      biological applications. The usefulness of [Eu-7] for monitoring Zn(2+) changes
      in living HeLa cells was confirmed. This novel Zn(2+)-selective luminescent
      lanthanide chemosensor [Eu-7]should be an excellent lead compound for the
      development of a range of novel luminescent lanthanide chemosensors for
      biological applications.

PMID- 15453782
TI  - Spectroscopic and computational studies of the azide-adduct of manganese
      superoxide dismutase: definitive assignment of the ligand responsible for the low
      temperature thermochromism.
AB  - A variety of spectroscopic and computational techniques have been used to examine
      the thermochromic transition previously reported for the oxidized state of Mn
      dependent superoxide dismutase from E. coli in the presence of substrate analog
      azide (N(3)-Mn(3+)SOD).[Whittaker, M. M.; Whittaker, J. W. Biochemistry 1996, 35,
      6762-6770.] Although previous spectroscopic studies had shown that this
      thermochromic event corresponds to a change in coordination number of the active
      site Mn(3+) ion from 6 to 5 as temperature is increased, the ligand that
      dissociates in this conversion had yet to be identified. Through the use of
      electronic absorption, circular dichroism (CD), and magnetic CD (MCD)
      spectroscopies, both d-->d and ligand-to-metal charge-transfer (LMCT) transition
      energies have been determined for native Mn(3+)SOD (possessing a five-coordinate
      Mn(3+) center) and Y34F N(3)-Mn(3+)SOD (forming a six-coordinate N(3)-Mn(3+)
      adduct at all temperatures). These two systems provide well-defined reference
      points from which to analyze the absorption and CD data obtained for N(3)
      Mn(3+)SOD at room temperature (RT). Comparison of excited-state spectroscopic
      data reveals that Mn(3+)SOD and RT N(3)-Mn(3+)SOD exhibit virtually identical d-
      >d transition energies, suggesting that these two species possess similar
      geometric and electronic structures and, thus, that azide does not actually
      coordinate to the active-site Mn(3+) ion at RT. However, resonance Raman spectra
      of both N(3)-Mn(3+)SOD and Y34F N(3)-Mn(3+)SOD at 0 degrees C exhibit azide
      related vibrations, indicating that azide does interact with the active site of
      the native enzyme at this temperature. To gain further insight into the nature of
      the azide/Mn(3+) interaction in RT N(3)-Mn(3+)SOD, several viable active-site
      models designed to promote either dissociation of coordinated solvent, Asp167, or
      azide were generated using DFT computations. By utilizing the time-dependent DFT
      method to predict absorption spectra for these models of RT N(3)-Mn(3+)SOD, we
      demonstrate that only azide dissociation is consistent with experimental data.
      Collectively, our spectroscopic and computational data provide evidence that the
      active site of N(3)-Mn(3+)SOD at RT exists in a dynamic equilibrium, with the
      azide molecule either hydrogen-bonded to the second-sphere Tyr34 residue or
      coordinated to the Mn(3+) ion. These results further highlight the role that
      second-sphere residues, especially Tyr34, play in tuning substrate (analog)/metal
      ion interactions.

PMID- 15453783
TI  - Unusual Ar-H/Rh-H J(HH) NMR coupling in complexes of rhodium(III): experimental
      evidence and theoretical support for an eta1-arene structure.
AB  - The synthesis and structural properties of three new hydridorhodium(III)
      complexes are reported. Hydrogenolysis of the cyclometalated rhodium dichloride
      complexes [RhCl(2)[(S,S)-benbox(Me(2))]] (2a-c) leads to formation of the new
      complexes [RhCl(2)(H)[(S,S)-ip-benbox(Me(2))H]] (3a-c) in 45% to 85% yield.
      Compounds 3a-c were found to have unusual features by NMR spectroscopy: in
      particular, downfield shifted aryl proton resonances (8.88-9.03 ppm) that were
      coupled to the rhodium hydride resonances. Using X-ray crystallographic studies,
      a variety of solid- and solution-state characterization techniques, and DFT
      calculations, these features were attributed to the presence of weak pi-type
      eta(1)-arene interactions in 3a-c.

PMID- 15453784
TI  - Single-molecule magnets: preparation and properties of low symmetry [Mn4O3(O2CPh
      R)4(dbm)3] complexes with S = 9/2.
AB  - The preparation and properties of [Mn(4)O(3)(O(2)CPh-R)(4)(dbm)(3)] (R = H, p-Me,
      p-OMe, and o-Cl; dbm(-) is the anion of dibenzoylmethane) single-molecule magnets
      (SMMs) with virtual C(S) symmetry are reported. They were prepared by controlled
      potential electrolysis in 26-80% yields. The structures comprise a distorted
      cubane core of virtual C(S) symmetry, in contrast to the other, more common
      complexes of this type with virtual C(3)(V) symmetry. Solid-state magnetic
      susceptibility data establish the complexes have S = 9/2 ground-state spins, and
      ac susceptibility studies indicate they are single-molecule magnets (SMMs).
      Magnetization vs dc field sweeps below 1.00 K reveal hysteresis loops confirming
      a SMM, with a very large step at zero applied field diagnostic of fast quantum
      tunneling of magnetization (QTM) through the anisotropy barrier. The fast QTM
      rate suggested a significant rhombic ZFS parameter E, as expected from the low
      (virtual C(S)) symmetry. This was confirmed by high-frequency electron
      paramagnetic resonance spectroscopy on polycrystalline and single-crystal
      studies. The results confirm the importance of symmetry on the QTM rates.

PMID- 15453785
TI  - Ca(2.5)Sr(0.5)GaMn2O8: diamagnetic Ga in control of the structural and electronic
      properties of a bilayered manganate.
AB  - The temperature dependence of the crystal structure and electronic properties of
      brownmillerite-like Ca(2.5)Sr(0.5)GaMn(2)O(8) has been studied by neutron powder
      diffraction and muSR spectroscopy. The results show that short-range 2D magnetic
      order begins to develop within the perovskite-like bilayers of MnO(6) octahedra
      approximately 50 K above the 3D Neel temperature of approximately 150 K. The
      bilayers show a structural response to the onset of magnetism throughout this
      temperature range whereas the GaO(4) layers that separate the bilayers only
      respond below the 3D ordering temperature. XANES spectroscopy shows that the
      sample contains Mn(3+) and Mn(4+) cations in a 1:1 ratio, and the behavior in the
      region of the Neel transition is interpreted as a local charge ordering. Electron
      diffraction and high-resolution electron microscopy have been used to show that
      the local microstructure is more complex than the average structure revealed by
      neutron diffraction, and that microdomains exist in which the GaO(4) tetrahedra
      show different orientations. It is argued that the bonding requirements of
      diamagnetic gallium control the electronic behavior within the perovskite-like
      bilayers.

PMID- 15453786
TI  - Frustrated beta-chloride elimination. Selective arene alkylation by alpha
      chloronorbornene catalyzed by electrophilic metallocenium ion pairs.
AB  - Single-site polymerization catalysts generated in situ via activation of
      Cp*MMe(3) (Cp* = C(5)Me(5); M = Ti, Zr), (CGC)MMe(2) (CGC =
      C(5)Me(4)SiMe(2)NBu(t)(); M = Ti, Zr), and Cp(2)ZrMe(2) with
      Ph(3)C(+)B(C(6)F(5))(4)(-) catalyze alkylation of aromatic molecules (benzene,
      toluene) with alpha-chloronorbornene at room temperature, to regioselectively
      afford the 1:1 addition products exo-1-chloro-2-arylnorbornane (aryl = C(6)H(5)
      (1a), C(6)H(4)CH(3) (1b)) in good yields. Analogous deuterium-labeled products
      exo-1-chloro-2-aryl-d(n)-norbornane-7-d(1) (aryl-d(n) = C(6)D(5) (1a-d(6)),
      C(6)D(4)CD(3) (1b-d(8))) are obtained via catalytic arylation of alpha
      chloronorbornene in either benzene-d(6) or toluene-d(8). Isolated ion-pair
      complexes such as (CGC)ZrMe(toluene)(+)B(C(6)F(5))(4)(-) and
      Cp(2)ThMe(+)B(C(6)F(5))(4)(-) also catalyze the reaction of alpha
      chloronorbornene in toluene-d(8) to give 1b-d(8) in good yields, respectively.
      Small quantities of the corresponding bis(1-chloronorbornyl)aromatics 2 are also
      obtained from preparative-scale reactions. These reactions exhibit turnover
      frequencies exceeding 120 h(-1) (for the Cp*TiMe(3)/Ph(3)C(+)B(C(6)F(5))(4)(-)
      catalyzed system), and chlorine-free products are not observed. Compounds 1 and 2
      were characterized by (1)H, (2)H, (13)C, and 2D NMR, GC-MS, and elemental
      analysis. The aryl group exo-stereochemistry in 1a and 1b is established using
      (1)H-(1)H COSY, (1)H-(13)C HMBC, and (1)H-(1)H NOESY NMR, and is further
      corroborated by X-ray analysis of the product 1,4-bis(exo-1-chloro-2
      norbornyl)benzene (2a). Control experiments and reactivity studies on each
      component step suggest a mechanism involving participitation of the metal
      electrophiles in the catalytic cycle.

PMID- 15453787
TI  - Molecular understanding of the formation of surface zirconium hydrides upon
      thermal treatment under hydrogen of [([triple bond]SiO)Zr(CH2tBu)3] by using
      advanced solid-state NMR techniques.
AB  - The reaction of [([triple bond]SiO)Zr(CH(2)tBu)(3)] with H(2) at 150 degrees C
      leads to the hydrogenolysis of the zirconium-carbon bonds to form a very reactive
      hydride intermediate(s), which further reacts with the surrounding siloxane
      ligands present at the surface of this support to form mainly two different
      zirconium hydrides: [([triple bond]SiO)(3)Zr-H] (1a, 70-80%) and [([triple
      bond]SiO)(2)ZrH(2)] (1b, 20-30%) along with silicon hydrides, [([triple
      bond]SiO)(3)SiH] and [([triple bond]SiO)(2)SiH(2)]. Their structural identities
      were identified by (1)H DQ solid-state NMR spectroscopy as well as reactivity
      studies. These two species react with CO(2) and N(2)O to give, respectively, the
      corresponding formate [([triple bond]SiO)(4-x)Zr(O-C(=O)H)(x)] (2) and hydroxide
      complexes [([triple bond]SiO)(4-x)Zr(OH)(x)] (x = 1 or 2 for 3a and 3b,
      respectively) as major surface complexes.

PMID- 15453788
TI  - Deuterium-labeling and NMR study of the dearomatization of N-alkyl-N
      benzyldiphenylphosphinamides through anionic cyclization: ortho and benzylic
      lithiation directed by complex-induced proximity effects.
AB  - The mechanism of the anionic cyclization dearomatizing reaction of N-benzyl-N
      methyldiphenylphosphinamide (1) upon treatment with s-BuLi in tetrahydrofuran
      (THF) at -90 degrees C has been analyzed by deuterium-labeling and natural
      abundance multinuclear magnetic resonance ((1)H, (2)H, (7)Li, (13)C, (31)P)
      studies. In the absence of coordinating cosolvents such as
      hexamethylphosphoramide (HMPA), eight major anionic species were identified,
      which allowed us to unravel the pathway of the metalation reaction. In agreement
      with the complex-induced proximity effect (CIPE) mechanism, the sequence of
      transformations emerging from this study involves the coordination of the lithium
      base to the P=O group of 1 to give four dimeric precomplexes whose NMR data are
      consistent with structures Va/Vb and VIIIa/VIIIb. The diastereomers Va/Vb are the
      precursors of the monomeric benzylic anion II, whereas the VIIIa/VIIIb
      diastereomers are assumed to undergo ortho deprotonation leading to anions I.
      Translocation from the ortho anion to the benzylic one is not observed.
      Intramolecular conjugate addition of anion II to the P-phenyl rings happens in a
      reversible way, affording the monomeric dearomatized anions III, IV, VI, and VII.
      The reaction progresses to yield a mixture containing only the species I, III,
      and IV. HMPA acts as a catalyst for the ortho-to-benzylic translocation and
      anionic cyclization reactions. Two-dimensional (2D) (7)Li,(31)P[(1)H] shift
      correlations and (7)Li[(31)P] NMR spectra proved to be crucial for the structural
      assignment of the anionic species. These techniques also demonstrated the
      diastereotopicity of the two achiral ligands involved in a dimer with s-BuLi (Vb)
      owing to the slow configuration inversion of the carbanion center.

PMID- 15453789
TI  - Biomimetic enantioselective total synthesis of (-)-siccanin via the Pd-catalyzed
      asymmetric allylic alkylation (AAA) and sequential radical cyclizations.
AB  - (-)-Siccanin (1), a natural product possessing significant antifungal properties,
      was synthesized enantioselectively via a biomimetic route. This synthetic route
      features two sequential radical cyclizations: a Ti(III)-mediated radical
      cyclization of epoxyolefin 48 to construct the B-ring, and a Suarez reaction to
      establish the tetrahyrofuran ring. Chiral chroman moiety of siccanin was prepared
      based on our recent development of the Pd-catalyzed asymmetric allylic alkylation
      (AAA) of phenol trisubstituted allyl carbonates. Several other members of the
      siccanin family were also synthesized including siccanochromenes A (2), B (3), E
      (6), F (7), and the methyl ether of siccanochromene C (55). These studies may
      shed light on the biosynthesis of this novel family of compounds.

PMID- 15453790
TI  - Catalytic asymmetric allylation of ketones and a tandem asymmetric
      allylation/diastereoselective epoxidation of cyclic enones.
AB  - A simple procedure is reported for the catalytic asymmetric allylation of
      ketones, utilizing titanium tetraisopropoxide, BINOL, 2-propanol additive, and
      tetraallylstannane as allylating agent. A variety of ketone substrates, including
      acetophenone derivatives and alpha,beta-unsaturated cyclic enones, reacted to
      form tertiary homoallylic alcohols in good yields (67-99%) and with high levels
      of enantioselectivity (generally >80%). A novel one-pot enantioselective
      allylation/diastereoselective epoxidation has also been introduced. Thus, upon
      completion of the allyl addition to conjugated cyclic enones, 1 equiv of tert
      butyl hydroperoxide is added and the directed epoxidation of the allylic double
      bond ensues to afford the epoxy alcohol with high diastereoselectivity.

PMID- 15453791
TI  - Spectroscopic demonstration of a large antisymmetric exchange contribution to the
      spin-frustrated ground state of a D3 symmetric hydroxy-bridged trinuclear Cu(II)
      complex: ground-to-excited state superexchange pathways.
AB  - The magnetic and electronic properties of a spin-frustrated ground state of an
      antiferromagnetically coupled 3-fold symmetric trinuclear copper complex (TrisOH)
      is investigated using a combination of variable-temperature variable-field
      magnetic circular dichroism (VTVH MCD) and powder/single-crystal EPR. Direct
      evidence for a low-lying excited S = (1)/(2) state from the zero-field split
      ground (2)E state is provided by the nonlinear dependence of the MCD intensity on
      1/T and the nesting of the VTVH MCD isotherms. A consistent zero-field splitting
      (Delta) value of approximately 65 cm(-1) is obtained from both approaches. In
      addition, the strong angular dependence of the single-crystal EPR spectrum, with
      effective g-values from 2.32 down to an unprecedented 1.2, requires in-state spin
      orbit coupling of the (2)E state via antisymmetric exchange. The observable EPR
      intensities also require lowering of the symmetry of the trimer structure, likely
      reflecting a magnetic Jahn-Teller effect. Thus, the Delta of the ground (2)E
      state is shown to be governed by the competing effects of antisymmetric exchange
      (G = 36.0 +/- 0.8 cm(-1)) and symmetry lowering (delta = 17.5 +/- 5.0 cm(-1)). G
      and delta have opposite effects on the spin distribution over the three metal
      sites where the former tends to delocalize and the latter tends to localize the
      spin of the S(tot) = (1)/(2) ground state on one metal center. The combined
      effects lead to partial delocalization, reflected by the observed EPR parallel
      hyperfine splitting of 74 x 10(-4) cm(-1). The origin of the large G value
      derives from the efficient superexchange pathway available between the ground
      d(x2-y2) and excited d(xy) orbitals of adjacent Cu sites, via strong sigma-type
      bonds with the in-plane p-orbitals of the bridging hydroxy ligands. This study
      provides significant insight into the orbital origin of the spin Hamiltonian
      parameters of a spin-frustrated ground state of a trigonal copper cluster.

PMID- 15453792
TI  - Structure-reactivity relationships in oxidative carbon-carbon bond forming
      reactions: a mild and efficient approach to stereoselective syntheses of 2,6
      disubstituted tetrahydropyrones.
AB  - Homobenzylic ethers with pendent enol acetate nucleophiles undergo highly
      efficient cleavage reactions followed by 6-endo cyclizations to form 2,6
      disubstituted tetrahydropyrones with excellent stereocontrol at room temperature
      in the presence of the mild oxidant ceric ammonium nitrate. Cyclizations proceed
      through either stabilized or nonstabilized oxocarbenium ions. Structure
      reactivity relationships are presented to provide a predictive guide for the
      design of radical cation cleavage processes. Unique sequences for preparing
      cyclization substrates based on stereoselective Lewis acid mediated acetal
      openings have been developed for the synthesis of complex substrates that are
      suitable for applications to the synthesis of biologically active natural
      products.

PMID- 15453793
TI  - Strong exchange interactions between two radicals attached to nonaromatic spacers
      deduced from magnetic, EPR, NMR, and electron density measurements.
AB  - A nitronyl-nitroxide (NIT) biradical D-NIT2 linked by a single double bond has
      been engineered and investigated in the solid state by a combination of X-ray
      diffraction, magnetic susceptibility measurement, EPR, as well as solid-state
      (1)H and (13)C NMR spectroscopies, and experimental electron density
      distribution. All techniques reveal that a double bond is a very efficient
      coupling unit for exchange interactions between two radical moieties. Using a
      Bleaney-Bowers model dimer (H = -JS(1)S(2)), a singlet-triplet energy gap of J = 
      460 K was found with the singlet state being the ground state. This very strong
      intramolecular interaction was confirmed by EPR measurements in CH(2)Cl(2)
      solution (6 10(-4) M) or dispersed in a polymer matrix at low concentration. In
      keeping with these unusual interactions, solid-state NMR signals of the biradical
      were found to be considerably less shifted than those found for related
      monoradicals. Temperature-dependent solid-state (13)C NMR spectra of D-NIT2
      confirmed the very strong intramolecular coupling constant (J = -504 K). The
      electron density distribution of D-NIT2 was measured by high resolution X-ray
      diffraction, which also revealed that this biradical is an ideally conjugated
      system. The in-depth characterization includes the deformation maps and the
      observed electron density ellipticities, which exhibit a pronounced sigma-pi
      character of the O-N-C=C-N-O cores in keeping with an efficient electronic
      delocalization along the alkene spacer.

PMID- 15453794
TI  - Acidities in cyclohexanediols enhanced by intramolecular hydrogen bonds.
AB  - Equilibrium gas-phase acidities of the six isomeric cyclohexanediols were
      measured in a Fourier transform ion cyclotron resonance mass spectrometer.
      Although all six cyclohexanediols have the same functional groups and similar
      structures, the acidities vary over 11 kcal/mol. This large difference is due
      mostly to the balance between hydrogen bonding and geometric strain. To
      understand the origins of the acidity differences in more detail, the
      conformations and energetics of the cyclohexanediols were studied using density
      functional theory, which gave good agreement with the experimental acidities.
      Finally, methanol-methoxide and methanol-methanol interactions were used as a
      model for the hydrogen bonding.

PMID- 15453795
TI  - Gas-phase synthesis, submillimeter spectra, and precise structure of monomeric,
      solvent-free CuCH3.
AB  - The most-studied organocopper, methylcopper (CH(3)Cu), has been synthesized for
      the first time as a monomer, free of other ligands or coordinated solvent, and
      detected using millimeter-wave rotational spectroscopy. The molecule was created
      in the gas phase by the reaction of copper vapor and several different
      precursors, including CH(4) and tetramethylsilane. An obvious symmetric top
      pattern was observed, indicative of C(3)(v) symmetry. For confirmation,
      rotational spectra of four isotopically substituted species, (65)Cu(12)CH(3),
      (63)Cu(12)CD(3), (63)Cu(13)CH(3), and (65)Cu(13)CH(3), were recorded as well,
      following large-scale syntheses of specifically labeled precursors. From this
      data set, accurate spectroscopic constants and a structure for CH(3)Cu were
      derived. The r(m)((2)) geometry shows the shortest alkyl carbon-copper(I) bond
      length known (1.8809 A) and a rather large H-C-H angle in the methyl group
      (109.88 degrees). The measured rotational and distortion constants are well
      reproduced by QCISD calculations. This study should allow further refinement of
      theoretical calculations on methylcopper and other organocopper derivatives,
      which are valuable synthetic intermediates in organic chemistry.

PMID- 15453796
TI  - First-principles calculation of the 17O NMR parameters in Ca oxide and Ca
      aluminosilicates: the partially covalent nature of the Ca-O bond, a challenge for
      density functional theory.
AB  - We apply density functional theory (DFT) to the calculation of the (17)O NMR
      parameters in Ca and Mg oxides and aluminosilicates. We study the accuracy of the
      Perdew, Burke, and Ernzerhof (PBE) generalized-gradient approximation to DFT in
      the description of these systems and the origin of the experimentally observed
      large dependence of the (17)O chemical shift on the alkaline earth ion. We find
      that (i) the partially covalent nature of the Ca-O bond has a huge impact on the
      O chemical shifts. The Ca-O covalence alone explains why in Ca oxides and
      aluminosilicates the (17)O chemical shifts are much more deshielded than those of
      the corresponding Mg compounds. (ii) The Ca-O covalence is overestimated by the
      PBE functional. Thus PBE-DFT is not able to reproduce the measured (17)O NMR
      parameters in Ca oxide and Ca aluminosilicates. (iii) It is possible to correct
      for the PBE-DFT deficiency in a simple and transferable way and to predict very
      accurate (17)O NMR parameters. Such accuracy allows us to assign the (17)O NMR
      spectra of two important model systems: the grossite aluminate (CaAl(4)O(7)) and
      the wollastonite (CaSiO(3)) silicate.

PMID- 15453797
TI  - Density functional theory studies of the [2]rotaxane component of the Stoddart
      heath molecular switch.
AB  - The central component of the programmable molecular switch recently demonstrated
      by Stoddart and Heath is [2]rotaxane, which consists of a cyclobis(paraquat-p
      phenylene) shuttle (CBPQT(4+))(PF(6)(-))(4) (the ring) encircling a finger and
      moving between two stations, tetrathiafulvalene (TTF) and 1,5-dioxynaphthalene
      (DNP). As a step toward understanding the mechanism of this switch, we report
      here its electronic structure using two flavors of density functional theory
      (DFT): B3LYP/6-31G and PBE/6-31G. We find that the electronic structure of
      composite [2]rotaxane can be constructed reasonably well from its parts by
      combining the states of separate stations (TTF and DNP) with or without the
      (CBPQT)(PF(6))(4) shuttle around them. That is, the "CBPQT@TTF" state,
      (TTF)(CBPQT)(PF(6))(4)-(DNP), is described well as a combination of the
      (TTF)(CBPQT)(PF(6))(4) complex and free DNP, and the "CBPQT@DNP" state, (TTF)
      (DNP)(CBPQT)(PF(6))(4), is described well as a combination of free TTF and the
      (DNP)(CBPQT)(PF(6))(4) complex. This allows an aufbau or a "bottom-up" approach
      to predict the complicated [n]rotaxanes in terms of their components. This should
      be useful in designing new components to lead to improved properties of the
      switches. A critical function of the (CBPQT(4+))(PF(6)(-))(4) shuttle in
      switching is that it induces a downshift of the frontier orbital energy levels of
      the station it is on (TTF or DNP). This occurs because of the net positive
      electrostatic potential exerted by the CBPQT(4+) ring, which is located closer to
      the active station than the four PF(6)(-)'s. This downshift alters the relative
      position of energy levels between TTF and DNP, which in turn alters the electron
      tunneling rate between them, even when the shuttle is not involved directly in
      the actual tunneling process. Based on this switching mechanism, the "CBPQT@TTF"
      state is expected to be a better conductor since it has better aligned levels
      between the two stations. A second potential role of the (CBPQT(4+))(PF(6)(-))(4)
      shuttle in switching is to provide low-lying LUMO levels. If the shuttle is
      involved in the actual tunneling process, the reduced HOMO-LUMO gap (from 3.6 eV
      for the isolated finger to 1.1 eV for "CBPQT@TTF" or to 0.6 eV for "CBPQT@DNP"
      using B3LYP) would significantly facilitate the electron tunneling through the
      system. This might occur in a folded conformation where a direct contact between
      free station and the shuttle on the other station is possible. When this becomes
      the main switching mechanism, we expect the "CBPQT@DNP" state to become a better
      conductor because its HOMO-LUMO gap is smaller and because its HOMO and LUMO are
      localized at different stations (HOMO exclusively at TTF and LUMO at CBPQT
      encircling DNP) so that the HOMO-to-LUMO tunneling would be through the entire
      molecule of [2]rotaxane. Thus an essential element in designing these switches is
      to determine the configuration of the molecules (e.g., through self-assembled
      monolayers or incorporation of conformation stabilizing units).

PMID- 15453798
TI  - On the interpretation of residual dipolar couplings as reporters of molecular
      dynamics.
AB  - The analysis of residual dipolar couplings from an ensemble of conformations to
      extract molecular dynamics is intricate. The very mechanism that is necessary to
      perturb overall molecular tumbling to generate nonvanishing residual dipolar
      couplings gives rise to convoluted data. The measured values are essentially
      weighted averages over conformations. However, the weights are not simply the
      populations of conformations. Consequently, the observed order parameter is not
      exactly the true measure of motion. In the case of paramagnetic alignment, the
      apparent order parameter is expected to depend on the number of torsions that
      separate the locus of interest from the paramagnetic site. In the case of
      alignment due to steric obstruction, the uneven selection of conformations by
      their differing Saupe order matrices leads to a bias in the residual dipolar
      couplings-probed molecular dynamics.

PMID- 15453799
TI  - H-bonding patterns in the platinated guanine-cytosine base pair and guanine
      cytosine-guanine-cytosine base tetrad: an electron density deformation analysis
      and AIM study.
AB  - The atoms in molecule theory (AIM) and electronic structure analysis are applied
      together to investigate H-bonding patterns in metalated nucleobase complexes. The
      influence of Pt on the intra GC base pair H-bonding has been found to reduce
      intra base pair H-bonding of N4(C)...O6(G) in the platinated GC pair and GCGC
      tetrad. The relaxation of geometry constrains in metalated nucleobases is found
      to be decisively important in the formation of novel molecular architectures from
      nucleobases and metal entities. The incorporation of the platinum in the GCGC
      tetrad benefits the formation of the unique CH...N (H5(C)...N1(G)) hydrogen bond
      pattern in the tetrad by offering improved geometric constraints rather than
      through changing the electronic properties around the H5(C) and N1(G) sites.
      Platination at the N7 of guanine reduces the deprotonation energy considerably.

PMID- 15453800
TI  - Water-assisted reaction mechanism of monozinc beta-lactamases.
AB  - Hybrid Car-Parrinello QM/MM calculations are used to investigate the reaction
      mechanism of hydrolysis of a common beta-lactam substrate (cefotaxime) by the
      monozinc beta-lactamase from Bacillus cereus (BcII). The calculations suggest a
      fundamental role for an active site water in the catalytic mechanism. This water
      molecule binds the zinc ion in the first step of the reaction, expanding the zinc
      coordination number and providing a proton donor adequately oriented for the
      second step. The free energy barriers of the two reaction steps are similar and
      consistent with the available experimental data. The conserved hydrogen bond
      network in the active site, defined by Asp120, Cys221, and His263, not only
      contributes to orient the nucleophile (as already proposed), but it also guides
      the second catalytic water molecule to the zinc ion after the substrate is bound.
      The hydrolysis reaction in water has a relatively high free energy barrier, which
      is consistent with the stability of cefotaxime in water solution. The modeled
      Michaelis complexes for other substrates are also characterized by the presence
      of an ordered water molecule in the same position, suggesting that this mechanism
      might be general for the hydrolysis of different beta-lactam substrates.

PMID- 15453801
TI  - A comparative analysis of localized and propagating surface plasmon resonance
      sensors: the binding of concanavalin a to a monosaccharide functionalized self
      assembled monolayer.
AB  - A comparative analysis of the properties of two optical biosensor platforms: (1)
      the propagating surface plasmon resonance (SPR) sensor based on a planar, thin
      film gold surface and (2) the localized surface plasmon resonance (LSPR) sensor
      based on surface confined Ag nanoparticles fabricated by nanosphere lithography
      (NSL) are presented. The binding of Concanavalin A (ConA) to mannose
      functionalized self-assembled monolayers (SAMs) was chosen to highlight the
      similarities and differences between the responses of the real-time angle shift
      SPR and wavelength shift LSPR biosensors. During the association phase in the
      real-time binding studies, both SPR and LSPR sensors exhibited qualitatively
      similar signal vs time curves. However, in the dissociation phase, the SPR sensor
      showed an approximately 5 times greater loss of signal than the LSPR sensor. A
      comprehensive set of nonspecific binding studies demonstrated that this signal
      difference was not the consequence of greater nonspecific binding to the LSPR
      sensor but rather a systematic function of the Ag nanoparticle's nanoscale
      structure. Ag nanoparticles with larger aspect ratios showed larger dissociation
      phase responses than those with smaller aspect ratios. A theoretical analysis
      based on finite element electrodynamics demonstrates that this results from the
      characteristic decay length of the electromagnetic fields surrounding Ag
      nanoparticles being of comparable dimensions to the ConA molecules. Finally, an
      elementary (2 x 1) multiplexed version of an LSPR carbohydrate sensing chip to
      probe the simultaneous binding of ConA to mannose and galactose-functionalized
      SAMs has been demonstrated.

PMID- 15453802
TI  - On the role of the conserved aspartate in the hydrolysis of the phosphocysteine
      intermediate of the low molecular weight tyrosine phosphatase.
AB  - The usual rate-determining step in the catalytic mechanism of the low molecular
      weight tyrosine phosphatases involves the hydrolysis of a phosphocysteine
      intermediate. To explain this hydrolysis, general base-catalyzed attack of water
      by the anion of a conserved aspartic acid has sometimes been invoked. However,
      experimental measurements of solvent deuterium kinetic isotope effects for this
      enzyme do not reveal a rate-limiting proton transfer accompanying
      dephosphorylation. Moreover, base activation of water is difficult to reconcile
      with the known gas-phase proton affinities and solution phase pK(a)'s of aspartic
      acid and water. Alternatively, hydrolysis could proceed by a direct nucleophilic
      attack by a water molecule. To understand the hydrolysis mechanism, we have used
      high-level density functional methods of quantum chemistry combined with
      continuum electrostatics models of the protein and the solvent. Our calculations
      do not support a catalytic activation of water by the aspartate. Instead, they
      indicate that the water oxygen directly attacks the phosphorus, with the
      aspartate residue acting as a H-bond acceptor. In the transition state, the water
      protons are still bound to the oxygen. Beyond the transition state, the barrier
      to proton transfer to the base is greatly diminished; the aspartate can abstract
      a proton only after the transition state, a result consistent with experimental
      solvent isotope effects for this enzyme and with established precedents for
      phosphomonoester hydrolysis.

PMID- 15453803
TI  - Accurate and efficient method for predicting thermochemistry of polycyclic
      aromatic hydrocarbons - bond-centered group additivity.
AB  - A self-consistent estimation method for the thermochemical properties of
      polycyclic aromatic hydrocarbons (PAH) is presented. This method is based on
      enthalpies of formation (DeltaHf(degrees), entropies (S(degrees)298, and heat
      capacities (C(degrees)p obtained from B3LYP/6-31G(d) calculations of the total
      energies and frequencies for 139 PAHs, including C(60) and C(70) fullerenes. The
      enthalpies of formation were calculated using an optimized set of homodesmic
      reactions given the available experimental DeltaHf(degrees) of PAHs. The
      theoretical entropies were compared with the existing experimental entropies, and
      some inconsistencies in the experimental data were identified. The estimation
      method presented here is a systematic extension of the widely employed atom
      centered group additivity method originally proposed by Benson. This new method
      is based on bond-centered groups that define bonds linking two atom-centered
      groups and specify the size of the rings to which they belong. In addition, a
      term to describe the resonance energy is included. The thermochemical properties
      of PAHs up to C(70) fullerene are estimated with a mean average deviation of 2.8
      kcal mol(-1) in DeltaHf(degrees), 0.7 cal K(-1) mol(-1) in S(degrees)298, and
      about 0.5 cal K(-1) mol(-1) in the C(degrees)p. This bond-centered group
      additivity method for the thermochemical properties of PAHs significantly expands
      both the range of systems that can be estimated and the accuracy of the
      estimations. The results of this work also allow us to assess the quality of
      available experimental data. For example, there are strong indications that the
      literature DeltaHf(degrees)of benzo[k]fluoranthene is about 10 kcal mol(-1) too
      low.

PMID- 15453804
TI  - Excited-state proton transfer reactions of 10-hydroxycamptothecin.
AB  - Time-resolved and steady-state emission characterization of 10
      hydroxycamptothecin reveals a rich but less complex proton-transfer behavior than
      its parent hydroxyquinoline. The electronic effect of the additional electron
      withdrawing ring makes the excited-state both less basic and more acidic than the
      parent and adds to the class of high-acidity excited-state proton donors in
      photochemistry and photobiology.

PMID- 15453805
TI  - Serum interleukin-8 is elevated in men with prostate cancer and bone metastases.
AB  - Aalinkeel et al. (1) have recently reported that gene expression of angiogenic
      factors correlates with metastatic potential of prostate cancer cells. The
      rationale for the study of Aalinkeel et al. is that a variety of growth factors,
      among them interleukin-8 (il-8), can induce angiogenesis (2). Further,
      parathyroid hormone related peptide (PTHrP) acts to induce il-8 production in
      prostate cancer cells via an intracrine pathway independent of its classical
      nuclear localization sequence. This novel pathway could mediate the effects of
      PTHrP on the progression of prostate cancer (3). We measured il-8 in the serum of
      39 men with biopsy-proven prostate cancer. Their average age was 69 +/- 9 (mean
      +/- SD). Serum il-8 was measured with an automated chemiluminometric high
      sensitivity il-8 protein assay (Immulite, Diagnostic Products Corporation, Los
      Angeles, CA). We noted a significant elevation of il-8 in men with bone
      metastases, diagnosed by Tc-99 MDP bone scan, when compared to men with localized
      disease (Figure 1). Aalinkeel et al. found that il-8 was significantly higher in
      the more metastatic PC-3 and DU-145 prostate cancer cell lines, when compared to
      the poorly metastatic LnCAP cells. The results of our study of il-8 in men with
      prostate cancer support the findings of Aalinkeel et al. Therefore, new anti
      angiogenic therapies targeting specific genes controlling prostate tumor
      metastasis may be of benefit in treating prostate cancer.

PMID- 15453806
TI  - Cassette-based digital mammography.
AB  - Over the past several years, digital mammography systems have been installed
      clinically across North America in small but growing numbers. A photostimulable
      phosphor-based full-field digital mammography image was evaluated in this
      investigation. Commonly known as computed radiography (CR), its use closely
      mimics the screen-film mammography paradigm. System performance using modulation
      transfer function (MTF) and detective quantum efficiency (DQE) metrics show
      MTF(2.5 mm(-1)) = 0.5, DQE(2.5 mm(-1)) = 0.3, and MTF(5.0 mm(-1)) = 0.2, DQE(5.0
      mm(-1)) = 0.05, for a 26 kVp beam, 0.03 mm molybdenum tube filtration, 4.5 cm
      tissue attenuation, and 15 mR incident exposure to the detector. Slightly higher
      DQE values were measured at 32 kVp with 0.025 mm rhodium tube filtration. CR
      mammography advantages include the ability to use existing mammography machines,
      where multiple rooms can be converted to "digital" operation, which allows
      overall cost savings compared to integrated digital mammography systems. Chief
      disadvantages include the labor-intensive handling of the cassettes prior to and
      after the imaging exam, lack of a direct interface to the x-ray system for
      recording technique parameters, and relatively slow processing time. Clinical
      experience in an IRB-approved research trial has suggested that digital
      mammography with photostimulable storage phosphors and a dedicated CR reader is a
      viable alternative to conventional screen-film mammography.

PMID- 15453807
TI  - Luminance and contrast performance of liquid crystal displays for mammographic
      applications.
AB  - Liquid crystal displays (LCDs) are gradually replacing cathode-ray tubes (CRTs)
      as the primary means of electronic display of digital radiographs. The transition
      from CRT to LCD is fueled by advantages of the LCD technology such as enhanced
      maximum luminance and smaller form factor. This transition is expected to extend
      to digital mammography as well. The purpose of this study was to report the on
      axis luminance and contrast performance of five medical-grade LCDs in terms of
      compliance with the DICOM grayscale display function (GSDF) and AAPM TG18
      guidelines. The display devices included two 3 Mpx monochrome LCDs (Planar Dome
      C3, and NDS 20.8" Nova), two 5 Mpx monochrome LCDs (NDS 21.3" Nova, and Totoku
      ME511L), and one 9 Mpx color LCD (IBM T221). The on-axis luminance values were
      measured at all 8-bit driving levels using the TG18-LN test patterns and a
      baffled luminance meter and the results averaged. The luminance data were
      analyzed according to the AAPM TG18 methodology. The measured L(min), L(max),
      mean DeltaJND/Deltap, and maximum local deviation in DeltaJND/Deltap from GSDF,
      kappa(256), ranged within 0.43-0.87 cd/m(2), 263-715 cd/m(2), 2.15-2.72, and 0.79
      1.46 intervals, respectively. While the values varied notably between different
      devices, all devices conformed to the TG18 criteria for primary class displays in
      terms of on-axis luminance response, and thus judged suitable for mammographic
      applications from on-axis luminance standpoint. Notwithstanding the findings,
      other factors such as matrix size, angular response, and color functionality
      should further be taken into consideration.

PMID- 15453808
TI  - Computerized detection of mass lesions in digital breast tomosynthesis images
      using two- and three dimensional radial gradient index segmentation.
AB  - Initial results for a computerized mass lesion detection scheme for digital
      breast tomosynthesis (DBT) images are presented. The algorithm uses a radial
      gradient index feature for the initial lesion detection and for segmentation of
      lesion candidates. A set of features is extracted for each segmented partition.
      Performance of two- and three dimensional features was compared. For gradient
      features, the additional dimension provided no improvement in classification
      performance. For shape features, classification using 3D features was improved
      compared to the 2D equivalent features. The preliminary overall performance was
      76% sensitivity at 11 false positives per exam, estimated based on DBT image data
      of 21 masses. A larger database will allow for further development and
      improvement in our computer aided detection scheme.

PMID- 15453809
TI  - Evaluation of intra- and inter-fraction motion in breast radiotherapy using
      electronic portal cine imaging.
AB  - Breast irradiation is one of the most challenging problems in radiotherapy due to
      the complex shape of the target volume, proximity of radiation sensitive normal
      structures and breathing motion. It was the aim of the present study to use
      electronic portal imaging (EPI) during treatment to determine intra- and inter
      fraction motion in patients undergoing radiotherapy and to correlate the
      magnitude of motion with patient specific parameters. EPI cine images were
      acquired from the medial tangential fields of twenty radiotherapy patients on a
      minimum of 5 days each over the course of their treatment. The treatments were
      administered using 10 MV X-rays and dynamic wedges on a Varian Clinac 2100CD
      linear accelerator. Depending on the incident dose and the angle of the wedge,
      between 4 and 16 images could be acquired in one session using an EPI device
      based on liquid ionization chambers (Varian). The border between lung and chest
      wall could be easily detected in all images and quantitative measurements were
      taken for the amount of lung in the field and the distance of the breast tissue
      from the field edges. Inter-fraction variability was found to be about twice as
      large as intra-fraction variability. The largest variability was detected in
      cranio/caudal direction (intra-fraction: 1.3 +/- 0.4 mm; inter-fraction: 2.6 +/-
      1.3 mm) while the lung involvement varied by 1.1 +/- 0.2 mm and 1.8 +/- 0.6 mm
      intra- and inter-fraction, respectively. This indicates that the effect of
      breathing motion on the amount of radiated lung was not of major concern in the
      patients studied. Of other patient specific parameters such as body weight,
      breast separation, field size and location of the target, only increasing age was
      significantly correlated with larger inter-fraction motion. Acquisition of EPI
      cine loops proved to be a quick and easy technique to establish the amount of
      patient movement during breast radiotherapy. The relatively small variability
      found in the present pilot study justifies considerations for more conformal dose
      delivery.

PMID- 15453810
TI  - Quantitative assessment of tumor vasculature and response to therapy in kaposi's
      sarcoma using functional noninvasive imaging.
AB  - Two noninvasive methods, thermography and laser Doppler imaging (LDI), were
      assessed for their ability to quantitatively assess parameters of vascularity in
      lesions of HIV-associated Kaposi's sarcoma (KS). Thermography and LDI images of a
      representative KS lesion were recorded in 16 patients and compared to normal skin
      either adjacent to the lesion or on the contralateral side. Eleven of the 16
      patients had greater than 0.5 degrees C increased temperature and 12 of the 16
      patients had increased flux (measured by LDI) as compared to normal skin. There
      was a strong correlation between these two parameters (R = 0.81, p < 0.001). In
      ten patients, measurements were obtained prior to therapy and after receiving a
      regimen of liposomal doxorubicin and interleukin-12. After 18 weeks of therapy,
      temperature and blood flow of the lesions were significantly reduced from the
      baseline (p = 0.004 and 0.002 respectively). These techniques hold promise to
      assess physiologic parameters in KS lesions and their changes with therapy.

PMID- 15453811
TI  - Enhanced cell growth inhibition following PTEN nonviral gene transfer using
      polyethylenimine and photochemical internalization in endometrial cancer cells.
AB  - PTEN is a tumor suppressor gene mapped on chromosome 10q23.3 and encodes a dual
      specificity phosphatase. PTEN has major implication in PI3 kinase (PI3K) signal
      transduction pathway and negatively controls PI3 phosphorylation. It has been
      reported to be implicated in cell cycle progression and cell death control
      through inhibition of PI3K-Akt signal transduction pathway and in the control of
      cell migration and spreading through its interaction with focal adhesion kinase.
      Somatic mutations of PTEN are frequently detected in several cancer types
      including brain, prostate and endometrium with more than 30% of tumor tissue
      specimens bearing PTEN mutations and/or deletions. Because of its high frequency
      of mutations and its important function as tumor suppressor gene, PTEN is a good
      candidate for gene therapy. Inducible expression of PTEN has been also reported.
      In cancer cells bearing PTEN abnormalities, the reversion of PTEN function by
      external gene transfer becomes more and more investigated in cancer treatment
      research. Several technologies including the photochemical internalization (PCI)
      and aiming at improving the transfection efficiency have been reported. PCI is an
      innovative procedure based on light-induced delivery of macromolecules such as
      DNA, proteins and other therapeutic molecules from endocytic vesicles to the
      cytosol of target cells. PCI has been reported to enhance the gene delivery
      potential of viral and nonviral vectors. The present study was designed to
      evaluate the influence of photochemical internalization on polyethylenimine (PEI)
      mediated PTEN gene transfer and its effects on the cellular viability in Ishikawa
      endometrial cancer cells bearing PTEN abnormalities. PCI was found to
      significantly (P < 0.01) enhance PTEN mRNA expression (4.2 fold increase).
      Subsequently, following PEI-mediated PTEN gene transfer, the restoration of the
      PTEN protein expression was observed. As a consequence, significant cell growth
      inhibition (44%) was observed in Ishikawa endometrial cells. Using PCI for PEI
      mediated PTEN gene transfer was found to further enhance PTEN mRNA and protein
      expression as well as PTEN-related cell growth inhibition reaching 89%.

PMID- 15453812
TI  - Gene therapy applications of viral vectors.
AB  - Viral vectors have frequently been applied in gene therapy with the final goal of
      treating various diseases in the areas of neurology, neurodegeneration, metabolic
      disease, and cancer. Vectors have been engineered based on AAV, adenoviruses,
      alphaviruses, herpes simplex viruses, lentiviruses, and retroviruses. Some
      vectors are suitable for short-term episomal transgene expression, whereas others
      are integrated into the host cell genome to provide long-term expression.
      Additionally, hybrid vectors with favorable features from different viruses have
      been developed. Therapeutic genes of choice have typically been toxic genes such
      as thymidine kinase, pro-apoptotic genes like Bax, and immunostimulatory genes
      (for instance, interleukin-12). A large number of animal studies have
      demonstrated proof of concept of viral gene therapy. Many types of viral vectors
      have been employed in more than 700 clinical trials that have been carried out or
      are currently in progress.

PMID- 15453813
TI  - The use of gene therapy in cancer research and treatment.
AB  - Gene therapy involves identifying a gene of interest and then manipulating the
      expression of this gene through a variety of techniques. Here we specifically
      address gene therapy's role in cancer research. This paper will encompass
      thoroughly investigated techniques such as cancer vaccines and suicide gene
      therapy and the latest advancements in and applications of these techniques. It
      will also cover newer techniques such as Antisense Oligonucleotides and small
      interfering RNAs and how these technologies are being developed and used. The use
      of gene therapy continues to expand in cancer research and has an integral role
      in the advancement of cancer treatment.

PMID- 15453814
TI  - Near infrared spectroscopy and imaging to probe differences in water content in
      normal and cancer human prostate tissues.
AB  - The content of water in cancerous and normal human prostate in vitro tissues was
      shown to be different using near infrared (NIR) spectroscopy. The water
      absorption peaks at 1444 nm and 1944 nm are observed in both types of prostate
      tissues. The measurements show that less water is contained in cancerous tissues
      than in normal tissues. The OH stretching vibrational overtone mode at 1444 nm
      and other water overtone modes provide key spectroscopic fingerprints to detect
      cancer in prostate tissue. Transmission and backscattered spectral imaging were
      measured in cancer and normal prostate tissues. The degree of polarization for
      700 nm, 800 nm, 1200 nm, and 1450 nm is larger for normal than for cancer
      tissues. The knowledge about water content offers a potential as a diagnostic
      tool to better determine and image cancer in prostate and in other tissues types
      such as breast and cervix using the absorption from vibrational overtones of
      H(2)O molecules in the NIR.

PMID- 15453815
TI  - Effects of high intensity focused ultrasound on vascular endothelial growth
      factor in melanoma bearing mice.
AB  - This study was to investigate the effects of high intensity focused ultrasound on
      vascular endothelial growth factor. A B16 melanoma model was adopted in our
      study. Melanoma bearing mice were randomly divided into two groups: HIFU group
      and surgery group. While the control group was only injected with isovolumetric
      normal saline solution and treated as the surgery group. We detected VEGF both in
      tissues and sera through immunohistochemical method and ELISA respectively.
      Tissues were sampled pre- and at the 3rd day post-operation in HIFU group and
      blood samples were taken pre- and at the 1st, 3rd, and 7th day post-operation in
      all the groups. As a result, in the tissues, VEGF was expressed in 80% melanomas,
      but none was detected in the targeted area after HIFU treatment. In the sera,
      there was a decreasing tendency of serum-VEGF concentrations in group HIFU and
      surgery after operation, while that in the control group increased after
      operation. The levels in the HIFU group on day 1, 3, and 7 postoperatively were
      all lower than that in the surgery group respectively (79.16 pg/ml vs 91.59
      pg/ml; 33.64 pg/ml vs 49.39 pg/ml; 30.37 pg/ml vs 46.68 pg/ml), but there wasn't
      any significant difference (P > 0.05). So HIFU can destroy VEGF in the targeted
      area and maybe have less of an effect on serum-VEGF than surgery.

PMID- 15453816
TI  - Biomarkers for risk assessment in molecular epidemiology of cancer.
AB  - One out of four deaths in the USA is due to cancer. Identification of populations
      at risk of developing cancer is important as it provides opportunities for
      prevention and treatment of cancer. Biomarkers are measurable indicators of
      exposure effects and susceptibility or disease state, and are used to understand
      the mechanisms of cancer progression. In recent molecular epidemiology studies
      genomic, proteomic, and epigenomic markers have been utilized which exhibit high
      sensitivity and specificity for different tumor types and can be assayed in
      biofluids and other specimens collected by non-invasive technologies. The current
      challenges and future directions in the field are discussed in this article.

PMID- 15453817
TI  - Transvenous cryoablation of cardiac arrhythmias.
AB  - This study reports on the acute and long-term results of cryoablation in patients
      with supraventricular and ventricular tachycardia. One hundred fifty nine
      patients with cardiac arrhythmias (147 with supraventricular and 12 with
      ventricular tachycardia) were consecutively enrolled in our institution to
      undergo trnasvenous cryoablation with a new cryotechnology system (CryoCor trade
      mark ). This cryoablation system consists of a console, an articulating arm
      housing a pre-cooler, and a disposable sterile steerable bipolar 10-fr catheter.
      The N(2)O is used as a main refrigerant. The acute and chronic outcomes (after 15
      months for patients with supraventricular tachycardia and 9 months for patients
      with ventricular tachycardia) were comparable to those using radiofrequency
      energy. From this study we concluded that transvenous cryoablation is a safe and
      effective therapy for the treatment of cardiac arrhythmias.

PMID- 15453820
TI  - Purification and initial characterization of a putative blue light-regulated
      phosphodiesterase from Escherichia coli.
AB  - The Escherichia coli protein YcgF contains a photosensory flavin adenine
      dinucleotide (FAD)-binding BLUF domain covalently linked to an EAL domain, which
      is predicted to have cyclic-di-guanosine monophosphate (GMP) phosphodiesterase
      activity. We have cloned, overexpressed and purified this protein, which we refer
      to as blue light-regulated phosphodiesterase (Blrp) for its putative activity.
      Blrp undergoes a reversible photocycle after exposure to light in which the
      spectrum of its photostationary state and kinetics of recovery of the dark state
      are similar to those of the isolated BLUF domain of the AppA protein. Unlike the
      AppA BLUF domain, the chromophore environment in the context of full-length Blrp
      is asymmetric, and the protein does not undergo any detectable global changes on
      exposure to blue light. When overexpressed in E. coli, Blrp copurifies with
      certain proteins which suggests that it plays a protective role in response to
      oxidative stress. Predicted proteins from Klebsiella pneumoniae and from a
      bacterium in the Sargasso Sea are similar to E. coli Blrp in both their BLUF and
      EAL domains, which suggests that blue light sensing in these bacteria may follow
      similar pathways.

PMID- 15453821
TI  - Multiplex polymerase chain reaction analysis of UV-A- and UV-B-induced delayed
      and early mutations in V79 Chinese hamster cells.
AB  - We previously reported that approximately 10% of V79 Chinese hamster fibroblast
      populations clonally derived from single cells immediately after irradiation with
      either ultraviolet B (UV-B, 290-320 nm, mainly 311 nm) or ultraviolet A (UV-A,
      320-400 nm, mainly 350-390 nm) radiation exhibit genomic instability. The
      instability is revealed by relatively high mutation frequencies in the
      hypoxanthine phosphoribosyl transferase (hprt) gene up to 23 cell generations
      after irradiation. These delayed mutant clones exhibited higher levels of
      oxidative stress than normal cells. Therefore, persistently increased oxidative
      stress has been proposed as a mechanism for UV-induced genomic instability. This
      study investigates whether this mechanism is reflected in the deletion spectrum
      of delayed mutant clones. Eighty-eight percent of the delayed mutant clones
      derived from UV-A-irradiated populations were found to have total deletion of the
      hprt gene. Correspondingly, 81% of UV-A-induced early mutations (i.e. detected
      shortly after irradiation) also had total deletions. Among delayed UV-B-induced
      mutant clones, 23% had total deletions and 8% had deletion of one exon, whereas
      all early UV-B events were either point mutations or small deletions or
      insertions. In conclusion, the multiplex polymerase chain reaction deletion
      screen showed that there were explicit differences in the occurrence of large
      gene alterations between early and delayed mutations induced by UV-B radiation.
      For UV-A radiation the deletion spectra were similar for delayed and early
      mutations. UV-A radiation is, in contrast to UV-B radiation, only weakly absorbed
      by DNA and probably induces mutation almost solely via production of reactive
      oxygen species. Therefore, the present results support the hypothesis that
      persistent increase in oxidative stress is involved in the mechanism of UV
      induced genomic instability.

PMID- 15453822
TI  - Global forecast model to predict the daily dose of the solar erythemally
      effective UV radiation.
AB  - A worldwide forecast of the erythemally effective ultraviolet (UV) radiation is
      presented. The forecast was established to inform the public about the expected
      amount of erythemally effective UV radiation for the next day. Besides the
      irradiance, the daily dose is forecasted to enable people to choose the
      appropriate sun protection tools. Following the UV Index as the measure of global
      erythemally effective irradiance, the daily dose is expressed in units of UV
      Index hours. In this study, we have validated the model and the forecast against
      measurements from broadband UV radiometers of the Robertson-Berger type. The
      measurements were made at four continents ranging from the northern polar circle
      (67.4 degrees N) to the Antarctic coast (61.1 degrees S). As additional quality
      criteria the frequency of underestimation was taken into account because the
      forecast is a tool of radiation protection and made to avoid overexposure. A
      value closer than one minimal erythemal dose for the most sensitive skin type 1
      to the observed value was counted as hit and greater deviations as
      underestimation or overestimation. The Austrian forecast model underestimates the
      daily dose in 3.7% of all cases, whereas 1.7% results from the model and 2.0%
      from the assumed total ozone content. The hit rate could be found in the order of
      40%.

PMID- 15453828
TI  - Crystal structure of human carbonic anhydrase II at 1.95 A resolution in complex
      with 667-coumate, a novel anti-cancer agent.
AB  - CA (carbonic anhydrase) catalyses the reversible hydration of carbon dioxide into
      bicarbonate, and at least 14 isoforms have been identified in vertebrates. The
      role of CA type II in maintaining the fluid and pH balance has made it an
      attractive drug target for the treatment of glaucoma and cancer. 667-coumate is a
      potent inhibitor of the novel oncology target steroid sulphatase and is currently
      in Phase 1 clinical trials for hormone-dependent breast cancer. It also inhibits
      CA II in vitro. In the present study, CA II was crystallized with 667-coumate and
      the structure was determined by X-ray crystallography at 1.95 A (1 A=0.1 nm)
      resolution. The structure reported here is the first for an inhibitor based on a
      coumarin ring and shows ligation of the sulphamate group to the active-site zinc
      at 2.15 A through a nitrogen anion. The first two rings of the coumarin moiety
      are bound within the hydrophobic binding site of CA II. Important residues
      contributing to binding include Val-121, Phe-131, Val-135, Leu-141, Leu-198 and
      Pro-202. The third seven-membered ring is more mobile and is located in the
      channel leading to the surface of the enzyme. Pharmacokinetic studies show
      enhanced stability of 667-coumate in vivo and this has been ascribed to binding
      of CA II in erythrocytes. This result provides a structural basis for the
      stabilization and long half-life of 667-coumate in blood compared with its rapid
      disappearance in plasma, and suggests that reversible binding of inhibitors to CA
      may be a general method of delivering this type of labile drug.

PMID- 15453829
TI  - Electrochemical redox transformations of T1 and T2 copper sites in native
      Trametes hirsuta laccase at gold electrode.
AB  - Mediatorless, electrochemically driven, redox transformations of T1 (type 1) and
      T2 copper sites in Trametes hirsuta laccase were studied by cyclic voltammetry
      and spectroelectrochemical redox titrations using bare gold electrode. DET
      (direct electron transfer) between the electrode and the enzyme was observed
      under anaerobic conditions. From analysis of experimental data it is concluded
      that the T2 copper site is in DET contact with gold. It was found that electron
      transfer between the gold surface and the T1 copper site progresses through the
      T2 copper site. From EPR measurements and electrochemical data it is proposed
      that the redox potential of the T2 site for high-potential 'blue' laccase is
      equal to about 400 mV versus NHE (normal hydrogen electrode) at pH 6.5. The
      hypothesis that the redox potentials of the T2 copper sites in low- and high
      potential laccases/oxidases from totally different sources might be very similar,
      i.e. approx. 400 mV, is discussed.

PMID- 15453830
TI  - FHL3 negatively regulates human high-affinity IgE receptor beta-chain gene
      expression by acting as a transcriptional co-repressor of MZF-1.
AB  - The high-affinity IgE receptor FcepsilonRI plays a key role in triggering
      allergic reactions. We recently reported that human FcepsilonRI beta-chain gene
      expression was down-regulated by a transcription factor, MZF-1, through an
      element in the fourth intron. In the present study, we found that this
      transcriptional repression by MZF-1 required FHL3 (four and a half LIM domain
      protein 3) as a cofactor. Yeast two-hybrid and immunoprecipitation assays
      demonstrated that FHL3 bound MZF-1 in vitro and in vivo. Overexpression of FHL3
      in KU812 cells suppressed the beta-chain promoter activity through the element in
      the fourth intron in an MZF-1-dependent manner. Furthermore, results from pull
      down assays and gel-filtration chromatography employing nuclear extracts
      indicated that MZF-1 and FHL3 formed a complex of high molecular mass with some
      additional proteins in the nucleus. Granulocyte-macrophage colony-stimulating
      factor, which was reported to decrease FcepsilonRI expression, induced the
      accumulation of FHL3 in the nucleus, in accordance with the repressive role of
      FHL3 in beta-chain gene expression.

PMID- 15453831
TI  - Adenoviral mediated gene transfer of PDGF-B enhances wound healing in type I and
      type II diabetic wounds.
AB  - We have shown that the genetically diabetic mouse (C57BLKS/J-m+/+Lepr(db)) has a
      wound healing and neovascularization deficit associated with an inability to
      recruit endothelial precursor cells (EPCs) to the wound. This may account for a
      fundamental mechanism in impaired diabetic wound healing. We hypothesized that
      the adenoviral mediated overexpression of platelet-derived growth factor-B (PDGF
      B) would enhance wound healing, improve neovascularization, and recruit EPCs to
      the epithelial wound in three diabetic mouse models. Eight-mm full-thickness
      flank wounds were made in db/db, nonobese NOD/Ltj, streptozotocin, and C57BLKS/J
      mice. Wounds were treated with either 1 x 10(8) PFU Ad-PDGF-B or Ad LacZ or
      phosphate buffered saline solution. Wounds harvested at seven days were analyzed
      for epithelial gap, blood vessel density, granulation tissue area, and EPCs per
      high powered field. All three diabetic models have a significant wound healing
      and neovascularization defect compared to C57BLKS/J controls. Adenoviral-PDGF-B
      treatment significantly enhanced epithelial gap closure in db/db, streptozotocin,
      and nonobese NOD/Ltj mice as compared to diabetic phosphate buffered saline
      solution or Ad LacZ controls. A similar increase in the formation of granulation
      tissue and vessel density was also observed. All three models had reduced levels
      of GATA-2 positive EPCs in the wound bed that was corrected by the adenoviral
      mediated gene transfer of PDGF. EPC recruitment was positively correlated with
      neovascularization and wound healing. Three different diabetic models have a
      wound healing impairment and a decreased ability to recruit EPCs. The vulnerary
      effect of adenoviral mediated gene therapy with PDGF-B significantly enhanced
      wound healing and neovascularization in diabetic wounds. The PDGF-B mediated
      augmentation of EPC recruitment to the wound bed may be a fundamental mechanism
      of these results.

PMID- 15453832
TI  - Calmodulin-myosin light chain kinase inhibition changes fibroblast-populated
      collagen lattice contraction, cell migration, focal adhesion formation, and wound
      contraction.
AB  - Wound healing requires fibroblast migration, synthesis of new extracellular
      matrix, and organization of that matrix, all of which depend upon myosin ATPase
      activation and subsequent cytoplasmic actin-myosin contraction. Myosin ATPase
      activity is optimized by phosphorylation of myosin light chain at serine 19.
      Several different signaling pathways can perform that phosphorylation, the focus
      here is calcium saturated calmodulin dependent -myosin light chain kinase (CaM
      MLCK). It is proposed that CaM-MLCK phosphorylation of myosin light chain and
      subsequent myosin ATPase activation affects granulation tissue fibroblast
      behavior and contributes to wound contraction. Myosin ATPase activity generates
      actin-myosin contraction within fibroblasts. Myosin ATPase activity is involved
      in ATP-induced cell contraction, the generation of focal adhesions, fibroblast
      migration, fibroblast populated collagen lattice (FPCL) contraction, and wound
      contraction. The MLCK inhibitors ML-9 and ML-7 inhibited ATP-induced cell
      contraction, fibroblast migration, FA formation, and FPCL contraction. The
      calmodulin inhibitors W7 and fluphenazine blocked rat open wound contraction. In
      addition, fluphenazine delayed re-epithelialization. These findings support the
      idea that fibroblast CaM-MLCK activity is essential for tissue repair. We
      speculate that inhibition of CaM-MLCK may reduce or prevent detrimental fibrotic
      contracture.

PMID- 15453833
TI  - Factor XIII V34L polymorphism modulates the risk of chronic venous leg ulcer
      progression and extension.
AB  - Low Factor XIII (FXIII) activity has been reported in the blood of patients with
      chronic venous leg ulcer (CVU). In vivo studies have described increased wound
      healing in CVU patients treated with FXIII concentrate, and in vitro studies have
      shown increased regenerative capacity in FXIII-treated fibroblasts. In addition,
      a common G-to-T polymorphism in the FXIIIA-subunit gene (V34L) significantly
      increases the activity and modifies the cross-linking properties of the FXIII
      molecule and this variant has been investigated as a protective factor against
      thrombosis, a recognized risk factor for CVU establishment. Therefore, the role
      of FXIII levels, FXIII V34L, FVR506Q, and FIIG20210A, common gene polymorphisms
      in the pathogenesis of CVU was investigated. Ninety-one patients with CVU and 195
      healthy controls (91 of them sex- and age-matched) were PCR-genotyped for the
      FXIIIV34L, FVR506Q, and FIIG20210A substitutions and FXIIIA-subunit levels were
      determined by immuno-electrophoresis. The extent of the venous ulcer surface in
      patients was measured by computer software. The allele frequency and the genotype
      distribution of the FXIII polymorphism did not show significant differences
      between the whole group of cases and controls as well as prothrombin variants
      did. On the contrary, the FVR506Q variant (FV Leiden) allele was more frequent in
      patients, yielding a significant OR value of 5.93 (95 percent CI, 1.83-19.17; p=
      0.003). Considering only CVU cases secondary to a post-thrombotic syndrome (n=
      24), FV Leiden yielded a greater OR value of 16.08 (95 percent CI, 4.33-59.6; p <
      0.0001). When the CVU cases were stratified by the three possible FXIII
      genotypes, a significant trend toward a lower mean value of the ulcerated area
      was clearly evident as the number of the polymorphic alleles (L34) increased in
      the genotype of patients (VV = 11.9 cm(2,)+/- 23.6; VL = 6.1 cm(2,)+/- 6.9; LL =
      4.1 cm(2,)+/- 2.8; p= 0.01). On the other hand, FXIIIA antigen levels were
      similar between CVU cases and matched controls, but 11 percent of cases had FXIII
      deficiency (FXIIIA </= 0.65 U/ml; p= 0.003) and they showed a greater mean
      extension of the lesion if compared with the remaining cases without FXIIIA
      deficiency (14.5 cm(2), +/- 20.2 vs. 9.0 cm(2), +/- 6.3; p= 0.08). We conclude
      that FXIII antigen levels and FXIII V34L polymorphism may play a crucial role in
      the complex cascade of CVU pathophysiology, being significantly related to the
      CVU progression and extension because of the direct effects they have on the
      FXIII molecular activity.

PMID- 15453834
TI  - Modulation of scar tissue formation using different dermal regeneration templates
      in the treatment of experimental full-thickness wounds.
AB  - The recovery of skin function is the goal of each burn surgeon. Split-skin graft
      treatment of full-thickness skin defects leads to scar formation, which is often
      vulnerable and instable. Therefore, the aim of this study was to analyze wound
      healing and scar tissue formation in acute full-thickness wounds treated with
      clinically available biopolymer dermal regeneration templates. Full-thickness
      wounds (3 x 3 cm) on both flanks of Gottingen mini pigs (n= 3) were treated with
      split-thickness skin graft alone or in combination with a 1-ethyl-3-(3
      dimethylaminopropyl)-carbodiimide (EDC) cross-linked-collagen scaffold, Integra,
      or a polyethyleneglycol terephthalate-polybutylene terephthalate (PEGT/PBT)
      scaffold. The wounds (n= 12 per group) were examined weekly for six weeks to
      evaluate graft take, contraction (planimetry), and cosmetic appearance.
      Histologic samples taken after one and six weeks were used to assess scaffold
      angiogenesis, biocompatibility, and scar tissue quality. In all wounds, one week
      postwounding graft take was between 93 and 100 percent. The control wound,
      treated with split-skin graft, showed little granulation tissue formation,
      whereas the EDC-collagen treated wounds showed two to three times more
      granulation tissue formation. The collagen scaffold was completely degraded
      within one week. The Integra and PEGT/PBT scaffolds showed angiogenesis only
      through two-thirds of the scaffold, which resulted in loss of integrity of the
      epidermis. Only basal cells survived, proliferated, and regenerated a fully
      differentiated epidermis within three weeks. Granulation thickness was comparable
      to collagen scaffold-treated wounds. After six weeks, control wounds showed a
      wound contraction of 27.2 +/- 6.1 percent, Integra-treated wounds 34.6 +/- 6.4
      percent, collagen scaffold-treated wounds 38.1 +/- 5.0 percent, and PEGT/PBT
      scaffold-treated wounds 54.5 +/- 3.9 percent. The latter wounds had significantly
      more contraction than wounds of other treatment groups. Microscopically, the
      control and collagen scaffold-treated wounds showed an immature scar tissue that
      was two times thicker in the EDC-collagen treated wounds. The Integra-treated
      wounds showed nondegraded collagen scaffold fibers with partly de novo dermal
      tissue formation and partly areas with giant cells and other inflammatory cells.
      The PEGT/PBT scaffold was almost completely degraded. Scaffold particles were
      phagocytosized and degraded intracellularly by clusters of macrophages. The scar
      tissue was in the early phase of ECM remodeling. In conclusion, this study showed
      that the rate of dermal tissue formation and scarring is influenced by the rate
      of scaffold angiogenesis, degradation, and host response induced by the scaffold
      materials.

PMID- 15453835
TI  - Histologic evaluation of skin-derived and collagen-based substrates implanted in
      palatal wounds.
AB  - Tissue shortage complicates the surgery of cleft lip and palate anomalies and the
      healing of defects on the palate impairs growth of the dento-alveolar complex due
      to scar tissue formation. Implantation of substitutes into the wound area might
      overcome this adverse effect. The aim of this study was to compare the tissue
      response to three collagen-based (collagen type I substrate alone, or collagen
      coated with elastin or chondroitin-6-sulfate) and two skin-derived substrates
      (unprocessed dermis and AlloDerm) after implantation into 12 dogs. Histology was
      performed at 3, 10, and 20 days postsurgery. We showed that all substrates were
      well tolerated. However, it is unclear whether AlloDerm was rapidly degraded or
      if it was sequestrated. There was no elastin or collagen present in these wounds.
      All collagen-based substrates showed good epithelial regeneration, although
      heparan sulfate (JM 403) was absent. Wounds treated with the collagen-based
      substrates contained fewer myofibroblasts at 20 days postsurgery and the type III
      collagen fibers in the immature scar tissue were more randomly oriented than in
      an untreated wound. In conclusion, palatal wounds with a dermal substrate heal
      with fewer indications of scar tissue formation and evoke only a mild
      inflammatory reaction, which is preferred over the tissue reaction in an
      untreated wound.

PMID- 15453836
TI  - Fascial fibroblast kinetic activity is increased during abdominal wall repair
      compared to dermal fibroblasts.
AB  - Abdominal wall fascial wound healing failure is a common clinical problem for
      general surgeons, manifesting in early postoperative fascial dehiscence as well
      as delayed development of incisional hernias. We previously reported that
      abdominal wall fascial incisions normally recover breaking strength faster than
      simultaneous dermal incisions in a rodent model. The accelerated fascial repair
      was associated with greater fibroblast cellularity within fascial wounds and
      increased wound collagen deposition. The current study was designed to determine
      whether accelerated fascial healing is the result of increased fascial fibroblast
      kinetic activity as measured by a more efficient fibroblast phenotype for binding
      to and remodeling a collagen matrix. Using a new model of abdominal wall repair,
      fibroblast cell cultures were developed from uninjured and wounded fascia and
      compared to dermal fibroblasts in order to define the fibroproliferative kinetic
      properties of abdominal wall fibroblasts. Fascial wound fibroblasts produced a
      more efficient and greater overall collagen lattice compaction compared to dermal
      fibroblasts. Acute fascial wound fibroblasts also showed enhanced cell
      proliferation compared to dermal fibroblasts but no significant differences in
      collagen production when normalized to cell number. These results suggest that
      fascial fibroblasts express distinct acute repair phenotypes and therefore a
      specific mechanism for fascial repair following injury.

PMID- 15453837
TI  - Complex epithelial-mesenchymal interactions modulate transforming growth factor
      beta expression in keloid-derived cells.
AB  - Keloids are proliferative dermal growths representing a pathologic wound healing
      response. We have previously demonstrated that coculture of fibroblasts derived
      from either keloid or normal skin have an elevated proliferation rate when
      cocultured with keloid-derived keratinocytes vs. normal keratinocytes. In these
      studies, we examined the contribution of transforming growth factor-beta (TGF
      beta) to this phenomenon using a two-chamber coculture system. Fibroblast
      proliferation in coculture was slower with the addition of a pan-TGF-beta
      neutralizing antibody. Keloid keratinocytes in coculture expressed more TGF
      beta1, -beta3, and TGF-beta receptor 1 than normal keratinocytes. Keloid
      fibroblasts cocultured with keloid keratinocytes expressed more mRNA for TGF
      beta1, -beta2, TGF-beta receptor 1, and Smad2. Keloid fibroblasts also produced
      more type I collagen, connective tissue growth factor, and insulin-like growth
      factor-II/mannose-6-phosphate receptor when cocultured with keloid keratinocytes
      vs. normal keratinocytes. Levels of total and activated TGF-beta activity
      increased when fibroblasts were cocultured with keratinocytes, correlating with
      the changes in transcriptional activity of TGF-beta. In conclusion, we find a
      complex paracrine interaction regulates TGF-beta mRNA expression and activation
      between keratinocytes and fibroblasts. These data suggest that keloid
      pathogenesis may result from both an increased TGF-beta production and activation
      by the keloid keratinocyte, and elevated TGF-beta expression, utilization, and
      signaling in keloid fibroblasts.

PMID- 15453838
TI  - Expression of transforming growth factor-beta and extracellular matrix by human
      peritoneal mesothelial cells and by fibroblasts from normal peritoneum and
      adhesions: effect of Tisseel.
AB  - We have previously shown that fibroblasts obtained from adhesions produce greater
      amounts of transforming growth factor-beta 1 (TGF-beta1) and extracellular matrix
      (ECM) molecules than normal fibroblasts isolated from normal peritoneum. The
      purpose of the current studies was to examine the effect of Tisseel (Baxter
      Healthcare Corporation, Glendale, CA), a fibrin sealant containing fibrinogen,
      aprotinin (a protease inhibitor), thrombin, and CaC1(2), on TGF-beta1 and ECM
      production by human peritoneal mesothelial cells, normal peritoneal fibroblasts,
      and adhesion fibroblasts. Multiplex reverse transcription-polymerase chain
      reaction using beta-actin as a housekeeping gene was used to determine mRNA
      levels of TGF-beta1 and ECM in these cells at 6, 12, 24, and 48 hours under
      normoxic conditions in the following treatment groups : fibrin sealant (Tisseel)
      alone; fibrin sealant with the two components diluted 1 : 2; fibrin sealant with
      the sealer protein component reconstituted without aprotinin (a protease
      inhibitor); fibrin sealant with the sealer protein component reconstituted
      without aprotinin (and both components diluted 1 : 2); fibrin sealant components
      diluted to physiologic concentrations; and control (culture media). The test
      compositions had little effect on TGF-beta1 mRNA expression in mesothelial cells
      and normal peritoneal fibroblasts, but resulted in a marked reduction of TGF
      beta1 from adhesion fibroblasts. Expression of type I collagen by human
      peritoneal mesothelial cells was not detected; the compositions reduced type I
      collagen mRNA expression by both types of fibroblasts. Type III collagen was
      detected at six hours, and increased approximately 50 percent by culturing for 48
      hours. Tisseel at full strength and with both components diluted 1 : 2 initially
      increased type III collagen mRNA levels; in contrast, type III collagen mRNA
      levels were reduced in mesothelial cells by the fibrin sealant without aprotinin
      at both concentrations and at physiologic concentrations. In both types of
      fibroblasts, the Tisseel compositions reduced type III collagen mRNA expression.
      Fibronectin mRNA were transiently reduced at six hours by approximately 50
      percent in the presence of the Tisseel components, but then returned to control
      levels. Fibronectin mRNA levels were not altered in normal peritoneal
      fibroblasts, but were reduced by all but the physiologic concentration in
      adhesion fibroblasts. Tisseel may modulate human peritoneal mesothelial cell,
      normal peritoneal fibroblast, and adhesion fibroblast function. These results
      suggest that fibrin sealant prepared from the Tisseel kit without aprotinin has
      the ability to reduce ECM and TGF-beta1 mRNA levels, especially from adhesion
      fibroblasts, which may indicate a role in reduction of postoperative adhesion
      development.

PMID- 15453839
TI  - K+ channel inhibition accelerates intestinal epithelial cell wound healing.
AB  - Restitution is the process by which superficial interruptions in the
      gastrointestinal mucosa are repaired by the flattening and spreading of
      epithelial cells surrounding the damage. During this process, mucosal epithelial
      cells undergo extensive reshaping and cytoskeletal remodeling. K(+) channels,
      located primarily on the basolateral surface of gut epithelial cells, are central
      to both actin polymerization, via their control of membrane potential, and cell
      volume regulation. We questioned whether K(+) channels are involved in
      restitution using an in vitro model of intestinal epithelium, monolayers of the
      human colon carcinoma cell line T84. We report that pharmacologic K(+) channel
      inhibition accelerates wound healing in T84 cell monolayers. Both Ca(++)
      dependent and constitutively active channels are involved, as indicated by the
      sensitivity to clotrimazole, charybdotoxin, and barium. The ability of
      clotrimazole to accelerate wound resealing was also observed in Caco-2 cell
      sheets. Pharmacologic stimulation of K(+) channel activity had no effect on the
      repair rate. Analysis of the resealing process by time lapse and confocal
      microscopy revealed that K(+) channel inhibitors abolished the initial wound
      retraction, briefly accelerated the repair rate, and altered the shape of the
      cell sheet abutting the injury during the early phase of resealing. We
      hypothesize that K(+) channel inactivation interrupts the coregulation of f-actin
      polymerization and volume control that is initiated by the healing process.

PMID- 15453840
TI  - Fluorescence imaging of reepithelialization from skin explant cultures on
      acellular dermis.
AB  - Reconstituted skin models are valuable tools in studies of cutaneous biology
      although they are not generally devised to visualize and quantify the time course
      of reepithelialization. We describe a skin explant culture technique coupled with
      vital microscopy allowing sequential imaging of epithelial outgrowth while
      maintaining the tissue in culture. Radial expansion of neo-epidermis was
      initiated from a 2-mm skin punch biopsy explanted onto acellular human dermis and
      maintained at the air-liquid interface in serum-containing keratinocyte medium.
      Microscopic viewings and surface area measurements of newly formed epidermis were
      performed repeatedly using fluorescein-based cell staining and subsequent image
      analysis. The labeling and visualization procedures did not interfere with neo
      epidermal growth or tissue architecture. In order to appraise the versatility of
      the model, we studied the effect of epidermal growth factor supplementation on
      the course of skin resurfacing as related to tissue morphology and proliferative
      activity over a 10-day cultivation period. Exogenous epidermal growth factor at
      10 ng/ml increased the radial outgrowth rate (mean, + 13.3 percent),
      papillomatosis index (+ 19.2 percent), epithelial thickness (+ 49.8 percent), and
      fraction of Ki-67 positive basal cells (+ 18.4 percent) in neo-epidermis produced
      from a biopsy of normal human skin. The contribution of this miniaturized and
      convenient format for concurrent studies of dynamic and qualitative features of
      neo-epidermis should be a useful complement to existing assays of
      epidermalization.

PMID- 15453844
TI  - Marius Tscherning (1854-1939): his life and work in optical physiology.
AB  - BACKGROUND: This article is based on Tscherning's papers, scientific protocols
      and letters and the many original instruments kept in the Medical History Museum
      in Copenhagen, Denmark. HISTORY: In 1884, after his thesis concerning the
      frequency of myopia in Denmark, Tscherning became adjunct director of the
      ophthalmological laboratory at the Sorbonne University in Paris. He was called
      back to Denmark in 1910 and appointed professor of ophthalmology and head of the
      Eye Department, Rigshospitalet. He continued to work scientifically as emeritus
      from 1925. ACHIEVEMENTS: Tscherning published about 100 scientific papers, mainly
      concerning optical physiology (i.e. the aetiology of myopia, entoptic phenomena,
      Purkinje pictures, the polygonal pattern provoked by corneal rubbing, etc.). He
      studied the law of Listing and projections depending on torsion of the eye and
      invented the ophthalmophacometer, which measures the changes that occur in the
      front and back curvatures of the crystalline lens during accommodation.
      Tscherning also studied aberration and calculated and constructed forward bulging
      periscopic (punctal) spectacle lenses. In addition, he studied colour sense, dark
      vision and adaptation.

PMID- 15453845
TI  - Have choroidal and ciliary body melanomas changed during the period 1955-2000?
AB  - PURPOSE: To establish whether the presentation of choroidal and ciliary body
      melanomas and patient survival have changed during the period 1955-2000. METHOD:
      The study included 209 unselected patients (97 men, 112 women) from Arhus County
      during the period 1955-2000. The median age at treatment was 64 years (range 26
      88 years). The disease course from first symptom through clinical and
      histopathological findings to death was described in a historical follow-up
      design. Time trends were evaluated. RESULTS: Treatment modality changed over time
      from enucleation to an almost equal distribution between enucleation and
      radiation brachytherapy. The age at treatment, or, alternatively, at diagnosis,
      increased significantly (p = 0.04). No significant time trend was seen for
      largest basal tumour diameter (p = 0.08) or tumour height (p = 0.27). The
      clinical and histopathological findings did not show any consistent time trends.
      No significant time trend was found for melanoma-specific survival (p = 0.96) or
      overall survival (p = 0.33). CONCLUSION: No consistent time trends were seen in
      clinical and histopathological tumour presentation and survival in patients with
      choroidal or ciliary body melanomas. The increase in age at treatment was in line
      with an increase in life expectancy in Denmark.

PMID- 15453846
TI  - Prognostic factors for survival after enucleation for choroidal and ciliary body
      melanomas.
AB  - PURPOSE: To evaluate prognostic factors for the survival of patients treated by
      enucleation for choroidal and ciliary body melanomas. METHODS: The study included
      293 consecutive patients (147 men and 146 women) treated by enucleation for a
      choroidal or ciliary body melanoma during the period 1955-2000. The median age at
      treatment was 61 years (range 26-88 years). Clinical and histopathological
      findings, vital status at October 1st, 2002, and cause of death were registered.
      Prognostic factors for survival were evaluated by univariate and multivariate Cox
      proportional hazards analysis and by Kaplan-Meier survival analysis. RESULTS:
      Follow-up was complete. The median follow-up time was 6.2 years (range 21 days to
      43.4 years) and the median potential follow-up time was 25.7 years (range 1.9
      47.7 years). In multivariate Cox proportional hazards analysis an increased risk
      of melanoma-related death was found for largest basal diameter (n = 264, p <
      0.001, mortality rate ratio (RR) = 1.09 for continuous parameter in mm), anterior
      tumour margin at the iris/ciliary body versus choroid (p < 0.001, RR = 2.22), and
      non-spindle cell type versus spindle cell (p = 0.047, RR = 1.45). An increased
      risk of death from all causes was found for men versus women (n = 266, p = 0.02,
      RR = 1.41), high age (p < 0.001, RR = 1.41 for continuous parameter in 10-year
      age groups), largest basal diameter (p < 0.001, RR = 1.07), anterior tumour
      margin at the iris/ciliary body (p = 0.02, RR = 1.52), and non-spindle cell type
      (p = 0.04, RR = 1.34). CONCLUSION: The risk of melanoma-related death after
      enucleation for a choroidal or ciliary body melanoma was high for tumours with
      large basal diameter, of non-spindle cell type and anterior location. Additional
      risk factors for death from all causes were male sex and high age.

PMID- 15453847
TI  - The occurrence and causes of registered blindness in diabetes patients in Arhus
      County, Denmark.
AB  - PURPOSE: To report the occurrence of registered blindness among diabetes patients
      in Arhus County, Denmark during 1993-2002. METHODS: Data were obtained from a
      database of 7527 diabetes patients, which included all patients in the county who
      had been treated for or had experienced visual loss due to diabetic retinopathy
      since 1992. Of these, 1949 had type 1 diabetes and represented 90% of the type 1
      diabetes patient population in the county, and 5459 had type 2 diabetes and
      represented 40% of the type 2 diabetes patient population in the county. RESULTS:
      The point prevalence of legal blindness was 0.6% for type 1 and 1.5% for type 2
      diabetes patients at January 1st, 2003. In type 1 diabetes patients, the major
      cause of blindness was proliferative diabetic retinopathy (PDR) (66.2% of all
      blind eyes); in type 2 diabetes patients the major causes were age-related
      macular degeneration (21.9%), PDR (18.0%) and diabetic maculopathy (DMac)
      (18.5%). During 1993-2002 there was a significant decrease in the number of blind
      eyes secondary to PDR (p = 0.008) in type 1 diabetes patients, and a significant
      increase in the number of blind eyes secondary to DMac (p = 0.005) in type 2
      diabetes patients. CONCLUSION: The major challenge in reducing diabetes-related
      blindness is related to the detection and treatment of an increased incidence of
      diabetic maculopathy in type 2 diabetes patients.

PMID- 15453848
TI  - Position of anterior capsulorhexis and posterior capsule opacification.
AB  - PURPOSE: To evaluate whether the position of the anterior continuous curvilinear
      capsulorhexis influences the rate of posterior capsule opacification (PCO).
      METHODS: A total of 119 patients, aged 61-86 years, underwent cataract surgery
      with phacoemulsification performed by a single surgeon. The patients were
      randomized to implantation with either a silicone intraocular lens (IOL) (SI40NB,
      Allergan) or an AcrySof IOL (MA60BM, Alcon). Three years after surgery, the rate
      of PCO was analysed using the evaluation of posterior capsule opacification
      computer software (EPCO). The results were related to the capsulorhexis position,
      which was assessed with a retroillumination photograph. RESULTS: If the
      capsulorhexis was located partially or completely off the optics of the IOL,
      compared to totally on the IOL, significantly more PCO was found (p = 0.0014).
      When comparing within each IOL type, patients with AcrySof IOLs were found to
      have significantly less PCO when the capsulorhexis was totally on the optic (p =
      0.0048). This difference was also significant in the silicone group (p = 0.041).
      CONCLUSION: A relatively small and central capsulorhexis allowing for the
      complete covering of the IOL optics by the rhexis edges seems to protect against
      PCO in cataract surgery, with both round-edged silicone IOLs and sharp-edged
      hydrophobic acrylic IOLs.

PMID- 15453849
TI  - An objective method to define outlier optical coherence tomograms and
      repeatability of retinal nerve fibre layer measurements.
AB  - PURPOSE: To compare the variation in thickness and reflectivity of the retinal
      nerve fibre layer (RNFL), circumferentially and on repeated testing. METHODS: In
      24 normal eyes and 38 eyes with different optic neuropathies or retinopathies,
      third-party optical coherence tomography (OCT) software defined the RNFL border
      based on the reflectivity pattern across the retina and also provided
      measurements of the mean reflectivity and total retinal thickness in addition to
      RNFL thickness. A new Gaussian filtering method was implemented so that the
      weight of the applied filter was varied for each of five individually repeated
      scans until an optimum weight filter was determined. RESULTS: The scans requiring
      the highest weight filter could be identified as 'outlier' scans that contained
      measurement or alignment artifacts. There was no difference in the weights of
      filtering needed for normal and abnormal eyes. The RNFL thickness and
      reflectivity, and retinal thickness were highly correlated with one another in
      normal and abnormal eyes. CONCLUSIONS: A new Gaussian filtering routine was
      devised that not only defined the most reproducible substructure of the RNFL for
      a given patient's eye, but also provided a new method of quantifying measurement
      variability and identification of scans with measurement or alignment artifacts.

PMID- 15453850
TI  - Refractive change after transscleral fixation of posterior chamber intraocular
      lenses in the absence of capsular support.
AB  - PURPOSE: To report the refractive change that occurred over 12 years after
      secondary transscleral fixation of posterior chamber intraocular lenses (PC
      IOLs). METHODS: A total of 21 patients who underwent transscleral fixation of PC
      IOLs were studied. We were able to follow 15 eyes of 15 patients for more than 12
      years. We evaluated refractive change in each patient for 12 years after the
      operation. RESULTS: The spherical refractive equivalent was -0.95 +/- 2.21 D
      immediately after the operation, -1.16 +/- 2.28 D after 2 years and -1.37 +/-
      1.94 D after 12 years. CONCLUSION: There were few changes in the spherical
      refractive equivalent up to 12 years after the operation.

PMID- 15453851
TI  - Using the KM visual acuity chart for more reliable evaluation of amblyopia
      compared to the HVOT method.
AB  - PURPOSE: To evaluate a new letter matching visual acuity (VA) chart (the KM
      chart) for children aged 5-7 years, designed as a Monoyer-based chart, in order
      to obtain a better consistency between school and preschool VA recordings.
      METHODS: Visual acuities were assessed using three methods: the HVOT, KM and
      Monoyer charts. Comparisons were made between the KM method versus the HVOT and
      Monoyer methods, respectively. Children with normal vision and with different
      degrees of amblyopia were investigated. RESULTS: Visual acuity levels appeared
      significantly higher in children with amblyopia when tested with the HVOT chart
      than when tested with the KM chart. Visual acuities obtained with the Monoyer and
      KM methods were comparable. The difference between the Monoyer and KM methods on
      the one hand, and the HVOT method on the other, can be explained by the fact that
      the HVOT chart elicits less crowding effect than the other two charts.
      CONCLUSIONS: Visual acuity in children with amblyopia might be overestimated if
      the HVOT test alone is used to assess vision. Use of the HVOT chart, therefore,
      should be restricted to the 3.5-4.5 years age group, for whom the KM chart is
      somewhat too difficult. In our opinion the KM chart should be preferred for use
      with older preschool children because it shows good consistency with the Monoyer
      chart.

PMID- 15453852
TI  - Excessive maternal caffeine exposure during pregnancy is cataractogenic for
      neonatal crystalline lenses in rats: a biomicroscopic and histopathologic study.
AB  - PURPOSE: To investigate histologically the influence of maternal caffeine
      exposure during pregnancy in vivo on crystalline lenses in neonatal rats.
      METHODS: Experimentally naive, female Wistar-albino rats (200-220 g) were mated
      with adult male rats over 2 days for copulation. After confirming pregnancy with
      a vaginal smear method, 50 gravid rats (dams) were randomly divided into five
      groups (n = 10 in each), consisting of one control and four experimental groups.
      Groups 1, 2 and 3 experimental dams were treated with intraperitoneal (i.p.)
      caffeine at doses of 25, 50 and 100 mg/kg/day, respectively, during pregnancy
      from gestational day 9 through to day 21. Group 4 dams were treated with caffeine
      in distilled water in a gavage at a dose of 50 mg/kg/day. Group 5 control dams
      were given i.p. saline solution daily for the same period. After normal delivery,
      the eyes were examined by slit-lamp biomicroscopy. The neonates were then killed
      by decapitation at postnatal days 1 or 30 and the eyes removed for
      histopathologic investigation of the lenses. RESULTS: Group 1 and control eyes
      had normal anterior lens capsules with a single layer of anterior cuboidal
      epithelial cells, regularly oriented cortical and nuclear lens fibres, and a
      clear posterior lens capsule with no lining epithelial cells behind the equator.
      In the remaining groups, histopathologic findings suggesting cataractogenesis
      included eosinophilic degeneration, lens fibre cell swelling and liquefaction,
      central lens fibres with retained nuclei, and prominent epithelial cells lining
      the posterior lens capsule behind the equator. Moreover, some lenses in group 3
      had immature cataract on slit-lamp biomicroscopic examination at postnatal day
      30. CONCLUSION: Excessive maternal caffeine exposure during pregnancy had
      cataractogenic effects on developing crystalline lenses in newborn rat eyes, both
      macroscopically and histopathologically. If an appropriate dose of caffeine can
      be identified, caffeine-induced cataract formation may be used as a new
      experimental cataract model in animal studies.

PMID- 15453853
TI  - Vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 in the
      regulation of corneal neovascularization and wound healing.
AB  - PURPOSE: To study the change in expression of vascular endothelial growth factor
      (VEGF) and its receptor VEGFR-2 in the rabbit cornea and limbus following a
      penetrating, central corneal alkali burn. The influence of different cells on
      VEGF and VEGFR-2 expression was studied by excluding granulocytes from the wound
      area. METHODS: Fourteen New Zealand white rabbits were subjected to a
      penetrating, 5-mm diameter, central corneal alkali burn in one eye under general
      anaesthesia. Seven of the rabbits were given injections of fucoidin for 36 hours.
      The rabbits were killed after 36 hours and the corneas were excised with a sclera
      rim and prepared for immunohistochemistry. RESULTS: Both VEGF and VEGFR-2 are
      strongly expressed in the frontline of repopulating epithelial, stromal and
      endothelial cells during wound healing, irrespective of granulocyte presence.
      Vascular endothelial cells express VEGF strongly after injury, but only in the
      presence of granulocytes. CONCLUSION: Corneal neovascularization requires the
      presence of granulocytes to stimulate vascular endothelial cells. During wound
      healing in this area, VEGF is a factor that stimulates proliferation and
      migration and that is not influenced by granulocytes.

PMID- 15453854
TI  - Ascorbic acid reversibly inhibits proliferation of retinal pigment epithelial
      cells.
AB  - PURPOSE: Proliferation control in adult retinal pigment epithelial (ARPE) cells
      is an essential factor in the clinical management of proliferative
      vitreoretinopathy (PVR). Factors which inhibit PVR and which are without toxic
      potential are therefore of interest in controlling proliferation. The aim of the
      present study was to gain insight into a possible function of high intraocular
      ascorbic acid levels as a physiological modulator of proliferation. METHODS:
      Adult retinal pigment epithelial cells were incubated in vitro with increasing
      concentrations of ascorbic acid (0.5-4 mmol, pH 7.4). Cell proliferation was
      assayed by the bromide-deoxy-uridine (BrdU) assay. The culture medium (CM)
      containing ascorbic acid was replaced with normal CM and the recovery of
      proliferation was measured after 24 hours. In order to be able to distinguish
      between proliferation inhibition, apoptosis, necrosis and recovery of
      proliferation, we performed TUNEL assays and fluorescence analysis cell-counter
      (FAC) analysis. RESULTS: Ascorbic acid significantly inhibits ARPE cell
      proliferation if it is present in concentrations above 2 mmol. Proliferation
      resumed in all ARPE cell cultures after pre-incubation with ascorbic acid,
      indicating that direct toxicity of ascorbic acid is a negligible factor. The time
      point and extent of recovery in proliferation was dependent on the initial
      ascorbic acid concentration. Fluorescence-labelled cell counts on apoptosis
      markers (FAC) data showed some induction of apoptosis and necrosis after
      incubation with 4 mmol ascorbic acid. CONCLUSIONS: Ascorbic acid has a dose
      dependent influence on the proliferation of vital ARPE cells. This possibly
      reflects the role of ascorbic acid at a physiological level within the vitreous
      cavity in preventing proliferative vitreoretinopathy (PVR). These findings may
      stimulate the development of new strategies in the clinical treatment of PVR.

PMID- 15453855
TI  - The protein kinase C system in focal adenitis of the lacrimal gland in the non
      obese diabetic mouse model for Sjogren's syndrome.
AB  - PURPOSE: Non-obese diabetic (NOD) mice develop an autoimmune exocrinopathy
      characterized by hyposecretion of saliva and acinar cell atrophy. As the protein
      kinase C (PKC) system is involved in the signal transduction pathways associated
      with primary secretion and acinar cell differentiation and growth, the PKC
      profile was analysed in NOD mice. METHODS: Lacrimal glands from BALB/c, NOD, NOD
      scid and transgenic NOD x interferon-gamma (IFN-gamma) mice were analysed for
      their PKC profiles using antibodies against several conventional (alpha, beta,
      gamma), novel (delta, epsilon, theta) and atypical (iota, lambda) PKC isoforms
      using the Streptavidin/HRP (horseradish peroxidase) method. RESULTS: Acinar cells
      in BALB/c control mice expressed two conventional (alpha, beta) and two atypical
      (iota, lambda) PKC isoforms. In NOD and transgenic NOD x IFN-gamma mice the same
      isoforms were more strongly expressed. NOD scid mice lacked all other PKC
      isoforms except PKC lambda. CONCLUSIONS: Co-expression of several PKC isoforms in
      single cell type may be necessary for transcriptional activation and agonist
      induced secretory responses. Hyposecretion in NOD mice was paradoxically
      associated with up-regulation of the PKC system. This may be associated with a
      deranged signal transduction per se rather than with the immune-inflammation, as
      the transgenic NOD x IFN-gamma mice showed similar PKC profiles. The NOD model
      does not reproduce lack/consumption of PKC II and PKC as in Sjogren's syndrome.
      This may be because the receptor autoantibodies in mice are directed against the
      adrenergic, not muscarinic, receptors. Lack and/or low level PKC expression in
      NOD scid mouse may explain the excessive acinar cell apoptosis in this model.

PMID- 15453856
TI  - Optical coherence tomography of a peripheral retinal schisis with an outer
      retinal layer break.

PMID- 15453857
TI  - External ophthalmomyiasis caused by Dermatobia hominis. A retrospective study of
      nine cases and a review of the literature.
AB  - PURPOSE: To report nine cases of external ophthalmomyiasis caused by Dermatobia
      hominis. METHODS: Retrospective, non-comparative, interventional case series.
      Participants consisted of patients (n = 9) presenting at Cayenne Hospital between
      1968 and 2003. The location and number of larvae, the larval stage, and the
      medical and surgical procedures applied were studied in each case. RESULTS: Seven
      patients had palpebral myiasis (including one with three larvae) and two had
      conjunctival myiasis. Every patient had palpebral oedema. The larval respiratory
      pore was located on the palpebral skin or free margin or on the conjunctiva.
      Movements were present within the lesion in at least three patients. Petroleum
      ointment or ivermectine solution was used in at least four patients to smother or
      kill the larvae. Extraction under local anaesthesia was possible in six patients,
      while three required general anaesthesia. CONCLUSION: Several larvae may be
      present in a patient. Topical ivermectine may help to kill the larvae before
      extraction is attempted.

PMID- 15453858
TI  - Transpupillary thermotherapy for the treatment of subfoveal choroidal
      neovascularization associated with age-related macular degeneration.
AB  - OBJECTIVE: To evaluate the efficacy of transpupillary thermotherapy (TTT) for the
      treatment of choroidal neovascularization (CNV) secondary to age-related macular
      degeneration (AMD). DESIGN: Prospective, non-randomized, non-masked, case
      selected series. METHODS: All patients with subfoveal CNV due to AMD and initial
      visual acuity (VA) between 6/9 and 6/60 were offered the opportunity to undergo
      TTT. Recruited subjects were treated using a diode laser (810 nm) with a beam
      size of 1.2-3.0 mm and power settings of 460-1200 mW. Treatment was applied for
      60 seconds in a subthreshold manner. MAIN OUTCOME MEASURES: Differences in VA and
      changes in the angiographic appearance of CNV. RESULTS: Thirty-one
      occult/predominantly occult and five classic/predominantly classic membranes were
      treated with TTT and were followed-up for a mean of 6.0 +/- 1.2 months. Following
      an average of 1.5 +/- 0.7 (range 1-4) laser sessions, VA remained stable ( -1 to
      +1 Snellen line) in 24 (66.7%) eyes, improved by > 1 line in two (5.6%) eyes and
      decreased significantly (> or = 2 Snellen lines) in 10 (27.8%) eyes.
      Angiographically confirmed closure of CNV was detected in 22 (61.1%) patients.
      Membranes persisted in 11 (30.6%) eyes and recurred in three (8.3%) eyes. There
      was no association between reduction, elimination or persistence of angiographic
      leakage of CNV and change in VA after treatment (p = 0.347). CONCLUSIONS:
      Transpupillary thermotherapy may be effective at preserving vision and reducing
      CNV leakage in a number of patients with exudative AMD. Further studies are
      required to compare TTT with the natural course of subfoveal CNV and alternative
      treatment options.

PMID- 15453859
TI  - Unilateral diabetic macular oedema secondary to central retinal vein congestion.
AB  - PURPOSE: To describe two cases of strictly unilateral diabetic retinopathy with
      macular edema where the precipitating factor appears to have been retinal venous
      congestion. METHODS: Retrospective interventional case study. RESULTS:
      Examination of fundus photographic records demonstrated generalized venous
      dilation in the affected eyes years in advance of the development of unilateral
      diabetic macular edema. Relentless progression of edema and visual loss followed
      despite retinal photocoagulation treatment and ultimately the affected eyes in
      both patients developed central retinal vein occlusion. The fellow eyes in both
      patients remained without retinopathy throughout the period of observation.
      CONCLUSION: The sequential and strictly unilateral appearance of retinal venous
      dilation, diabetic macular edema, and central retinal vein occlusion in diabetic
      patients without fellow-eye retinopathy suggests that venous congestion induced
      the progression from hyperglycemic insult to vascular injury in the affected
      eyes. Presumably, diabetes may cause retinal vascular dysfunction that results in
      little or no vascular damage unless venous congestion is present. This supports
      that venous congestion and increased sensitivity to congestion are important
      components of the pathogenesis of diabetic macular edema.

PMID- 15453860
TI  - Skin burn, bilateral iridocyclitis and amnesia following a lightning injury.
AB  - PURPOSE: To describe a case of lightning injury restricted to the eyes and facial
      skin. METHODS: Case history describing the clinical examination of a 54-year-old
      woman. RESULTS: Following a lightning stroke the patient suffered from a sharply
      demarcated facial skin burn and bilateral iridocyclitis with raised intraocular
      pressure. Initially she had amnesia regarding the incident. She recovered on
      symptomatic treatment, with dry eyes as the only sequela. CONCLUSION: We suggest
      that a lightning current travelled over the outside of the patient's body
      facilitated by her wet raincoat, a so-called flash-over. Thereby, she was spared
      from more severe injury, and only the exposed areas of the face and eyes were
      affected.

PMID- 15453861
TI  - Neurosarcoidosis mimicking Sjogren's syndrome.
AB  - PURPOSE: To describe a patient with a long disease history who was finally
      diagnosed with neurosarcoidosis and to discuss the reasons behind the delayed
      diagnosis. CASE REPORT: A 58-year-old man with sick sinus syndrome and
      bradycardia, which was treated with a pacemaker, developed first right and then
      left facial palsy. Subsequently, multiple cranial nerve palsies developed and
      later spontaneously resolved. Neurosarcoidosis was suspected at that stage, but
      excluded because the patient had no typical sarcoid lung changes, his serum and
      cerebrospinal fluid angiotensin converting enzyme activity levels were normal and
      a computed tomography scan disclosed no central nervous system changes. During
      follow-up, the patient developed extremely dry eyes and mouth, suggesting
      Sjogren's syndrome. Rheumatology consultation did not reveal any autoimmune or
      visceral features typical of Sjogren's syndrome and autoantibodies were negative.
      However, both labial salivary gland and conjunctival biopsies revealed non
      caseating granulomas, and neurosarcoidosis was diagnosed. CONCLUSIONS:
      Neurosarcoidosis is a relatively rare disease with a somewhat poor longterm
      prognosis in one-third of cases, although the neurological manifestations often
      diminish or disappear in response to glucocorticoid treatment. Diagnosis is often
      a clinical challenge, especially in the absence of pulmonary changes or other
      features typical of sarcoidosis. The labial salivary gland and conjunctiva
      provide helpful biopsy sites for histopathological confirmation of the diagnosis.

PMID- 15453862
TI  - Pneumocephalus and presumed meningitis following inconspicuous penetrating
      periocular trauma.
AB  - PURPOSE: To report a case of serious intracranial complications in an adolescent
      youth following a seemingly trivial periocular injury. METHODS: An adolescent
      youth was examined and discharged after a small penetrating injury to his left
      medial canthus. He later presented with blurred vision, nausea and mild pyrexia
      and underwent a computed tomography (CT) scan of the head and orbits as well as a
      lumbar puncture. RESULTS: The CT scan revealed a fracture in the cribriform plate
      of the ethmoid bone and the medial orbital wall, as well as pneumocephalus. The
      lumbar puncture revealed 3000 white cells/mm3 in the cerebrospinal fluid (CSF).
      After treatment with meningitic doses of intravenous antibiotics, a significant
      improvement was noted. CONCLUSIONS: A CT scan, instead of an ordinary head
      radiograph, may be considered as a first-choice mode of diagnosis in evaluating
      even inconspicuous penetrating periocular wounds. Early administration of
      meningitic doses of antibiotics may significantly improve prognosis.

PMID- 15453863
TI  - An unusual pathogen causing microbial keratitis.
AB  - INTRODUCTION: We report a rare case of Mycobacterium fortuitum affecting the
      corneal graft of a patient 6 years post-graft, possibly associated with contact
      lens use. CONCLUSIONS: This case shows the need for careful microbiological
      techniques when dealing with patients presenting with microbial keratitis. It
      must be kept in mind that unusual and slow growing organisms may also be
      responsible for corneal ulceration. If a slow growing organism is suspected, a
      microbiological diagnosis may not be forthcoming for weeks. Misidentification of
      the responsible pathogen may further complicate management for the clinicians.
      Cases such as these, which may not respond to medical therapy as expected, may
      prove a difficult therapeutic challenge to physicians.

PMID- 15453864
TI  - Optical coherence tomography in a case of Bietti's crystalline dystrophy.
AB  - PURPOSE: To demonstrate the cross-sectional morphology in crystalline
      retinopathy. METHODS: A 24-year-old woman with Bietti's crystalline dystrophy
      (BCD) and bilaterally decreased vision and nyctalopia was examined by optical
      coherence tomography (OCT). RESULTS: Fundus examination demonstrated numerous
      reflective, yellow-white crystalline deposits scattered throughout the posterior
      pole and midperipheral retina. Optical coherence tomography disclosed an
      abnormally level of high reflectivity in red to orange colours throughout the
      entire neuroretina, retinal pigment epithelium (RPE) and choroid. The RPE
      choriocapillaris complex was thickened and hyper-reflective, corresponding with
      dense crystalline deposits. CONCLUSION: The observed uncommon hyper-reflectivity
      in BCD relates to the deposition of numerous infiltrates. In vivo investigations
      by OCT confirmed histological studies that a crystalline retinopathy corresponds
      with numerous infiltrates in the retina, RPE and choroid. The RPE and choroid
      have intensive hyper-reflection and may be the primary location of the disease.

PMID- 15453865
TI  - Functional and anatomic results of macular hole surgery complicated by massive
      indocyanine green subretinal migration.
AB  - PURPOSE: To report the functional and anatomic results of macular hole (MH)
      surgery complicated by massive subretinal migration of indocyanine green (ICG)
      dye. DESIGN: Interventional case report. METHODS: We performed standard pars
      plana vitrectomy surgery for a stage 3, senile idiopathic MH. After posterior
      vitreous detachment and vitreous removal, we instilled 2 ml of ICG (0.5%, 270
      mOsm); the surgery was complicated by diffuse subretinal migration of the ICG dye
      but peeling of the internal limiting membrane (ILM) was performed (despite the
      obvious difficulties from the low contrast between the green-stained ILM
      overlying a green-stained subretinal space) and the rest of the procedure was
      completed with a final injection of 16% C3F8. RESULTS: Post-surgical optical
      coherence tomography confirmed the anatomic closure of the MH. Digital
      photography with the excitation and barrier filters for ICG showed a striking
      autofluorescence along the inferior vascular arcade, which remained intense 7
      months after surgery. Despite the massive subretinal migration of ICG, visual
      acuity (VA) improved to 20/30. CONCLUSIONS: This is the first report of VA
      recovery despite massive subretinal migration of ICG dye during MH surgery.
      Subretinal migration of ICG dye may be a potential complication during MH
      surgery; this should alert the surgeon to limit its use, despite the possible
      absence of clinically apparent toxic effects.

PMID- 15453866
TI  - Enhanced S-cone syndrome in a Japanese family with a nonsense NR2E3 mutation
      (Q350X).
AB  - PURPOSE: To describe the clinical characteristics of a Japanese male patient with
      enhanced S-cone syndrome (ESCS) and investigate the existence of mutations in the
      NR2E3 gene, which encodes a photoreceptor cell-specific nuclear receptor.
      METHODS: Fundus examinations, fluorescein angiography, colour vision tests,
      spectral sensitivity, and full-field and spectral electroretinography were
      performed. Mutation screening of the NR2E3 gene was performed with polymerase
      chain reaction (PCR) amplification and direct sequencing. RESULTS: We identified
      a novel homozygous mutation (c.1048C > T), that converts glutamine (CAA) to a
      termination codon (TAA) at amino acid position 350. The subject's unaffected
      parents were heterozygous for the mutation, consistent with autosomal recessive
      transmission. The electroretinographic findings revealed that the patient had
      neither rod nor 30-Hz flicker responses but did have cone responses with large a
      wave and low b-wave amplitudes, similar to the rod-plus-cone responses, and also
      substantial short wavelength-sensitive (S) cone and extremely diminished
      long/middle wavelength-sensitive (L/M) cone responses. In the right eye, spectral
      sensitivity in the fovea revealed both functional S-cone and remarkably reduced L
      and M-cone sensitivities, which was compatible with the decreased visual acuity
      (VA) and red/green colour vision defects noted in this eye. In contrast, the
      patient had good VA and normal red/green colour vision in the left eye.
      CONCLUSION: The nonsense mutation results in a truncated NR2E3 protein lacking 61
      amino acids within the ligand-binding domain (LBD) that consists of 190 amino
      acids of the C-terminus end. Therefore, null function of the LBD is likely to
      cause ESCS in the patient. The clinical findings for this patient suggest that
      his left eye, with its functional L/M- and S-cones, was at an earlier stage of
      the syndrome than his right eye.

PMID- 15453867
TI  - First case of post-conception Verteporfin exposure: pregnancy and neonatal
      outcome.
AB  - PURPOSE: To assess pregnancy and neonatal outcomes in a woman accidentally
      exposed to Verteporfin photodynamic therapy in the third week of pregnancy.
      METHODS: Post-conception counselling and prospective follow-up by telephone
      interview at Telefono Rosso (Teratology Information Service) were carried out.
      The baby was examined at birth and at 26 months. RESULTS: The outcome of the
      pregnancy was normal and a healthy female child with a normal birthweight was
      born. The baby's follow-up was normal at 26 months. CONCLUSIONS: This is the
      first reported case of a childbearing woman being accidentally exposed to
      Verteporfin during pregnancy. No fetal or neonatal adverse effects were
      documented.

PMID- 15453868
TI  - Visual dysfunction and methotrexate.

PMID- 15453869
TI  - Keratoglobus surgery: penetrating keratoplasty redux.

PMID- 15453870
TI  - A case of lymphangiectasia haemorrhagica conjunctivae following
      phacoemulsification.

PMID- 15453871
TI  - Choroidal neovascular membrane associated with malignant melanoma presenting as
      angle closure glaucoma.

PMID- 15453872
TI  - A case of ocular ochronosis and chronic open-angle glaucoma: merely coincidental?

PMID- 15453873
TI  - Nevocellular nevus of the palpebral conjunctiva.

PMID- 15453874
TI  - Large congenital posterior staphylomas.

PMID- 15453875
TI  - Vitreous opacities in a case of familial amyloidotic polyneuropathy associated
      with a transthyretin Lys 54.

PMID- 15453876
TI  - Chronic prephthisical ocular hypotony treated by intravitreal triamcinolone
      acetonide.

PMID- 15453878
TI  - Urogynecology today and in the future.

PMID- 15453879
TI  - Introduction of a new surgical procedure for treatment of female urinary
      incontinence.

PMID- 15453880
TI  - Postpartum urinary retention.

PMID- 15453881
TI  - A systematic review of the effects of estrogens for symptoms suggestive of
      overactive bladder.
AB  - OBJECTIVE: To perform a systematic review of the effects of estrogen therapy on
      symptoms suggestive of overactive bladder (OAB) in postmenopausal women.
      MATERIALS AND METHODS: This analysis involved a literature review of Medline,
      Excerpta Medica, and the Science Citation Index and a manual search of popular
      urology, gynecology, gerontology, and primary care medicine journals from January
      1969 to December 1999. Articles had to include estrogen and placebo treatment
      groups, published or original data presented at a scientific meeting and report
      symptoms suggestive of OAB. This search identified 11 randomized trials and
      included a total of 430 subjects. Thirty-six subjects who participated in two
      crossover studies received both estrogen and placebo and thus are counted twice,
      therefore 236 received estrogen therapy and 230 were placebo controls. Estrogen
      was administered systemically or locally as estriol, estradiol, conjugated
      estrogen, or estradiol and estriol. A meta-analysis of these studies was
      performed for all estrogen therapies and then separately for systemic and local
      therapies. RESULTS: Overall, estrogen therapies were associated with
      statistically significant improvements in all outcome variables: diurnal
      frequency (P = 0.0011), nocturnal frequency (P = 0.0371), urgency (P = 0.0425),
      number of incontinence episodes (P = 0.0002), first sensation to void (P =
      0.0001), and bladder capacity (P = 0.0018). Local therapies had statistically
      significant beneficial effects on all outcome variables. However, systemic
      therapies were only associated with significant improvements in incontinence
      episodes and first sensation to void while nocturnal frequency actually worsened.
      CONCLUSION: Estrogen therapy may be effective in alleviating the symptoms
      suggestive of OAB. Local administration may be the most beneficial route of
      administration.

PMID- 15453882
TI  - A new retropubic suspension operation technique for transvaginal Burch operation,
      using newly developed equipment.
AB  - BACKGROUND: Genuine stress urinary incontinence is a very common pathologic
      condition among women. In order to operate this, different techniques have been
      introduced. Here, a new technique is described for the operation of genuine
      stress urinary incontinence with newly developed equipment. The present technique
      offers more advantages than previous techniques introduced by different authors.
      With this technique, the duration of operation and of the recovery period are
      both shorter than with previous techniques. All patients had symptoms and signs
      of stress urinary loss. We performed multichannel cystometry preoperatively to
      all patients. METHOD: A special valve is used with reflector having 97%
      reflection capacity for transvaginal burch operation technique. Twenty five women
      (n = 25) having genuine stress urinary incontinence were taken under transvaginal
      Burch bladder neck suspension operation with fixation of suspension sutures to
      the Cooper (iliopectineal) ligament. RESULTS: Following urodynamic workup 6
      months after the surgery, one out of the 25 patients (4%) was diagnosed to have
      genuine stress incontinence, while one patient (4%) were diagnosed as having
      urinary stress incontinence and detrussor instability. One patient was found to
      be wet postoperatively due to only detrussor instability (4%). There were no
      significant differences pre- and postoperatively regarding capacity, residual
      volume, pressure rise on filling or standing, or maximal voiding pressure or peak
      flow rate.

PMID- 15453883
TI  - How important is TVT location?
AB  - BACKGROUND: The tension-free vaginal tape (TVT) is claimed to be a midurethral
      procedure, but data on sling placement are scarce to date. The aim of this study
      was to investigate tape position and mobility and correlate this with
      postoperative symptoms of bladder dysfunction. METHODS: One hundred and forty-one
      women 5 weeks to 2.1 years (mean 0.66 years) after TVT placement took part in a
      prospective clinical observational study. Appointments consisted of standardized
      symptom questionnaire, clinical stress test flowmetry and translabial ultrasound.
      The main outcome measures were patient symptoms, subjective satisfaction and
      cure/improvement. Paired t-test and anova statistics were employed for
      continuous, normally distributed parameters. RESULTS: Tape position varied from
      30 mm above to 12.7 mm below the symphysis at rest and between 15 mm above to
      18.7 mm below the symphysis on Valsalva. The horizontal distance of the tape from
      the symphysis pubis was weakly associated with recurrent stress incontinence (p =
      0.048). More cranial tapes were weakly associated with urge incontinence (p =
      0.03), frequency (p = 0.048) and symptoms of voiding dysfunction (p = 0.029).
      There was no association between tape placement and patient satisfaction or
      subjective cure/improvement. CONCLUSIONS: Position and mobility of the TVT vary
      markedly. This may be explained by varying degrees of dissection, localization of
      incisions and the preoperative degree of anterior vaginal wall prolapse. However,
      variations in placement seem to have relatively little effect on symptoms.

PMID- 15453884
TI  - Urinary tract infection in the users of depot-medroxyprogesterone acetate.
AB  - BACKGROUND: The effects of progesterone on muscle tone, peristalsis of the ureter
      and also urinary vasculature may cause urinary tract infection (UTI) in women who
      use depot-medroxyprogesterone acetate (DMPA) for contraception. METHODS: In a
      cohort study, 200 women who chose DMPA for contraception were compared with 200
      women who used the withdrawal method for urinary infection and urological
      symptoms after 3 months of consumption. RESULTS: The rate of urinary infection
      and urological symptoms in the study group were higher than in the control group
      (p = 0.018, p < 0.0001, respectively). The most common microorganism that caused
      urinary infection was Escherichia coli. Among the 10 cases who suffered UTI in
      the case group, there were six women who had UTI in the previous pregnancy as
      well. CONCLUSION: We do not recommended administering depot-medroxyprogesterone
      acetate for contraception in women with a history of urinary tract infection in a
      previous pregnancy.

PMID- 15453885
TI  - Is stress urinary incontinence a familial condition?
AB  - BACKGROUND: Stress urinary incontinence (SUI) is a common problem of
      multifactorial origin. Some authors have claimed that it has a familial
      predisposition. This study was undertaken to investigate the prevalence of SUI
      among first-degree relatives of 154 women who had been operated on for this
      disorder and of 100 women without SUI. METHODS: This report is concerned with a
      questionnaire-based, case-control study. A total of 154 women who had undergone
      operations for SUI and 100 women who denied having SUI were included. A
      comparison was made of 413 first-degree relatives of incontinent women and 372
      first-degree relatives of continent women according to the demographic
      characteristics, obstetric and gynecologic history and risk factors for SUI. The
      prevalence of SUI was investigated among the relatives. Furthermore, the
      characteristics of the women who had SUI operation were compared according to the
      continence state of their families. RESULTS: The prevalence of SUI was 71.4%
      among mothers and 24.6% among sisters of operated women compared with 40.3% among
      mothers and 11.6% among sisters of continent women (p < 0.05). Furthermore, the
      age at which symptoms began was significantly lower in the members of the
      'incontinent families' (p < 0.001). CONCLUSIONS: The relatives of incontinent
      women displayed a higher prevalence of SUI than the relatives of continent women.
      Although this condition has a multifactorial origin, the familial aggregation of
      SUI and the appearance of symptoms at younger ages in women with a family history
      of SUI suggest that heredity may play a significant role.

PMID- 15453886
TI  - Sphincter rupture and anal incontinence after first vaginal delivery.
AB  - BACKGROUND: The aim of this prospective study was to establish the incidence of
      anal incontinence and sphincter defects after first vaginal delivery. METHODS: A
      total of 99 nulliparous and pregnant women were examined prospectively 4 weeks
      (mean) before delivery and 4 months (mean) after delivery. Of the study
      population, 75 (76%) women had vaginal delivery and 24 (24%) had cesarean
      section. Vacuum extraction was necessary in 20 (20%) cases. The symptoms of anal
      incontinence were asked about using a standard questionnaire. Clinical
      examination, endoanal ultrasound (EAUS) and anal manometry were performed before
      and after delivery. RESULTS: The symptoms of mild anal incontinence, mainly gas
      incontinence, increased after vaginal delivery more than after cesarean section
      (P < 0.032). Occult anal sphincter defects were noted in 17 (23%) of the 75 women
      after vaginal delivery by using EAUS. After vacuum extraction, anal sphincter
      defects were noted in nine (45%) out of 20 women. No new sphincter defects were
      found in the cesarean section group. The maximal squeezing pressures were
      significantly decreased in the patients with external anal sphincter (EAS)
      defects (P = 0.0025). Vacuum extraction leads to more sphincter defects but does
      not significantly increase anal incontinence or decrease mean anal sphincter
      pressures. CONCLUSIONS: The first vaginal delivery can result in occult sphincter
      defects and the use of vacuum extraction increases the risk.

PMID- 15453887
TI  - Risk of postpartum urinary incontinence associated with pregnancy and mode of
      delivery.
AB  - AIM: The aim was to estimate the postpartum urinary incontinence (PP UI) impact
      of precursory UI during pregnancy (PR UI) and delivery performed by cesarean
      section (CS) vs. vaginal childbirth (VC). METHODS: Among the members of two
      population samples, in total 8610 women aged 20-59 years, 1232 had their first
      childbirth and 642 their second childbirth within 13-120 months prior to
      responding to a questionnaire that included information on PR UI occurrence, mode
      of delivery and PP UI occurrence. RESULTS: CS was applied in 12.2% of first
      childbirths, and 87.8% thus delivered vaginally; PR UI during the pregnancy
      leading to the first childbirth was reported by 15.6%, and a total of 26.3%
      reported PP UI. An increased PP UI occurrence was reported following VC (28.3%
      vs. 12.0% in women undergoing CS, p < 0.001) and after PR UI (first childbirth,
      66.7% vs. 18.8% in women not reporting PR UI, p < 0.0001). Among cases of PP UI
      following the first childbirth, 56.1% and 69.5% of cases could be attributed to
      PR UI and VC, respectively. CONCLUSIONS: The highest PP UI risks were found among
      women complaining of PR UI, which manifested itself as a crucial, independent
      precursor of PP UI. Because of the high frequency of VC, more than seven out of
      10 cases of UI following the first childbirth, however, seemed to be attributable
      to VC. The present data did not lend significant support to the assumption that
      the PP UI risk is also lowered after a subsequent delivery by CS.

PMID- 15453888
TI  - Symptoms of stress incontinence 1 year after childbirth: prevalence and
      predictors in a national Swedish sample.
AB  - BACKGROUND: The aims of the present study were to describe the prevalence of
      stress incontinence, as described by women themselves, 1 year after childbirth in
      a national sample of Swedish-speaking women, and to identify possible predictors.
      METHODS: A cohort study, including 2390 women recruited from 593 antenatal
      clinics in Sweden during three 1-week periods evenly spread over 1 year (1999
      2000), representing 53% of women eligible for the study and 75% of those who
      consented to participate. Data were collected by means of questionnaires in early
      pregnancy, 2 months and 1 year after the birth, and from the Swedish Medical
      Birth Register. RESULTS: One year after the birth, 22% of the women had symptoms
      of stress incontinence but only 2% said it caused them major problems. The
      strongest predictor was urinary incontinence (overall leakage) 4-8 weeks after a
      vaginal delivery (OR 5.5, CI 95% 4.1-7.4) as well as after a cesarean section (OR
      11.9, CI 95% 2.9-48.1). Other predictors in women with a vaginal delivery were:
      multiparity (OR 1.4; CI 95% 1.1-1.8), obesity (OR 1.6; CI 95% 1.1-2.4) and
      constipation 4-8 weeks postpartum (OR 1.4; CI 95% 1.1-1.9). CONCLUSION: Stress
      incontinence 1 year after childbirth is a common symptom, which could possibly be
      reduced by identifying women with urinary leakage at the postnatal check-up.

PMID- 15453889
TI  - Tension free vaginal tape: a procedure for all ages.
AB  - OBJECTIVE: To assess the success and complications of the tension free vaginal
      tape (TVT) procedure in different age groups. PATIENTS AND METHODS: This
      prospective long-term study of 179 consecutive cases of urodynamically confirmed
      urinary incontinence that had had the TVT procedure was conducted from March 1999
      to December 2002 at a District General Hospital. To assess whether outcome was
      influenced by the patient's age, the patients were divided into three age groups:
      group A (30-49 years old), group B (50-69 years old) and group C (70-90 years
      old). Operative details and early and late complications were recorded, and
      patients were followed up with clinic visits at 6 weeks and 6 months and a
      quality of life questionnaire was completed at 1 year. RESULTS: Of the 179
      patients included in the study, 53 (29.6%) were in group A, 91 (50.8%) in group B
      and 35 (19.5%) in group C. The subjective cure rate for the patients was 84.9%,
      81.3% and 85.3% in groups A, B and C, respectively. A significant improvement in
      symptoms was reported by 3.8%, 14.3% and 8.6% women, respectively. The failure
      rate was 11.3%, 4.4% and 5.7%, respectively. The intraoperative complication rate
      was 5.6%. The overall postoperative complication rate was 29.6%. A total of 86.2%
      of the patients were treated as day cases. Patients who had intraoperative
      complications or initial voiding difficulties (i.e. those patients requiring
      "in/out" catheterization before spontaneous voiding was established) were in
      hospital for 1-2 days. CONCLUSIONS: Our data showed better subjective cure rates
      and substantial improvement rates without any significant increase in
      intraoperative complications with increasing age. Postoperative complications of
      urgency and vaginal wall erosion were more common in the older aged patients but
      were easily resolved. Hospital stay and recovery period were short, making TVT a
      suitable procedure for all ages.

PMID- 15453891
TI  - Transient urinary retention and chronic neuropathic pain associated with genital
      herpes simplex virus infection.
AB  - BACKGROUND: Genital herpes (GH) causes genital ulcer disease, severe transient
      pain, and often paresthesias. Whether or not GH can cause urinary retention or
      chronic neuropathic pain is not well known. METHODS: We present two
      immunocompetent patients with GH associated with neuropathic symptoms. We also
      review the literature on GH and associated neurologic problems. RESULTS: Patient
      1 had primary herpes simplex virus (HSV)-2 infection with transient urinary
      retention and chronic bilateral neuropathic pain in the sacral area. Patient 2
      had recurrent HSV-1 associated with unitaleral chronic neuropathic pain in the
      sacral area. Although transient urinary retention associated with GH is not
      uncommon, chronic neuropathic pain has not been reported previously. CONCLUSIONS:
      Our cases show that chronic neuropathic pain, that is "pain initiated or caused
      by a primary lesion or dysfunction in the nervous system," can follow genital HSV
      infection.

PMID- 15453890
TI  - Stress urinary incontinence 4 years after the first delivery: a retrospective
      cohort survey.
AB  - BACKGROUND: Our aim was to estimate the prevalence of stress urinary incontinence
      4 years after the first delivery and analyze its risk factors. METHODS: A
      retrospective cohort survey was conducted in a French university hospital. The
      669 primiparous women who delivered in our department in 1996 a singleton in a
      vertex position between 37 and 41 weeks of amenorrhea were included. A mailed
      questionnaire was sent 4 years after the indexed delivery. The main outcome
      measure was stress urinary incontinence 4 years after the first delivery.
      RESULTS: Three hundred and seven women replied, 274 had moved and 88 did not
      respond. Four years after the first delivery, prevalence of stress urinary
      incontinence was 29% (89/307). According to multiple logistic regression
      analysis, the independent risk factors were urine leakage before the first
      pregnancy [odds ratio (OR) 18.7; 95% confidence interval (CI) 3.6-96.4], urine
      leakage during the first pregnancy (OR 2.5; 95% CI 1.3-4.8), duration of first
      labor > or = 8 h (OR 3.1; 95% CI 1.7-5.7), mother's age > 30 years at the first
      delivery (OR 2.4; 95% CI 1.4-4.2) and cesarean section at the first delivery (OR
      0.3; 95% CI 0.1-0.9). CONCLUSION: Our results suggest that stress urinary
      incontinence after pregnancy arises from a multifactorial condition. The main
      risk factors are: age, previous incontinence (before or during the first
      pregnancy), prolonged labor and vaginal delivery.

PMID- 15453892
TI  - Combined genital prolapse repair reinforced with a polypropylene mesh and tension
      free vaginal tape in women with genital prolapse and stress urinary incontinence:
      a retrospective case-control study with short-term follow-up.
AB  - BACKGROUND: To evaluate the tension-free vaginal tape (TVT) in both stress
      urinary incontinence (SUI) and occult SUI as an associated procedure at the time
      of tension-free polypropylene mesh repair for the treatment of genitourinary
      prolapse. METHODS: Forty-eight consecutive women undergoing surgery for genital
      prolapse and concurrent SUI from November 1999 to September 2002. Preoperatively,
      SUI was symptomatic in 29 women and occult in 19, with a positive stress test
      during repositioning of the prolapse. All patients had urethral hypermobility and
      none had intrinsic sphincter deficiency. The cystocele repair was performed in
      all patients according to the technique of tension-free polypropylene mesh.
      Twenty-six women had an associated TVT and 22 had no associated procedure for SUI
      (control group). The main outcome measures were postoperative SUI, voiding
      dysfunction, and recurrence of prolapse. RESULTS: The median follow-up was 20 +/-
      10.1 months (range 7-41). Patient characteristics and preoperative urodynamic
      evaluation were similar in the two groups. In patients with preoperative SUI,
      postoperative SUI occurred in 1/15 of the TVT group (6.7%) vs. 5/14 (35.7%) in
      the control group (p < 0.05), and voiding dysfunction occurred in 2/15 patients
      of the TVT group (13.3%) vs. 0/14 in the control group (p > 0.05). In patients
      with preoperative occult SUI, postoperative SUI occurred in 0/11 of the TVT group
      vs. 1/8 (12.5%) in the control group (p > 0.05), and voiding dysfunction occurred
      in 3/11 patients of the TVT group (27.3%) vs. 0/8 in the control group (p <
      0.05). Anatomic success on prolapse was 88.5% (23/26) and 86.4% (19/22) in the
      TVT and the control group, respectively (p > 0.05). CONCLUSION: In patients with
      preoperative SUI, TVT is more efficient than prosthetic cystocele repair alone to
      prevent postoperative SUI, without differences in voiding dysfunction. In
      patients with preoperative occult SUI, prosthetic cystocele repair is as
      efficient as TVT, with a decreased risk of voiding dysfunction.

PMID- 15453893
TI  - Urinary complications and sexual function after the tension-free vaginal tape
      procedure.
AB  - OBJECTIVE: The purpose of this prospective study was to evaluate urinary and
      sexual function after the tension-free vaginal tape (TVT) support procedure for
      stress urinary incontinence (SUI). METHODS: Between January 1999 and July 2002 a
      total of 71 patients underwent comprehensive examination including urodynamics
      and a mailed self-administered questionnaire for assessment of voiding and sexual
      function before and after treatment of SUI by TVT. RESULTS: Based on objective
      findings TVT was considered as curative in 48 patients (87.3%). Comparison of
      preoperative and postoperative urodynamic evidence demonstrated a significant
      outflow obstruction (<12 ml/s) in 19 patients (34.5%). A significant decrease in
      peak urinary flow during voiding (p < 0.001) was also observed. Of the 55 women
      (78.5%) who responded to the questionnaire before and after TVT, 42 (76.3%)
      reported satisfaction with the outcome. Postoperatively, 60% of patients reported
      voiding difficulty, 47.2% complained of urgency, and 32.7% of frequency.
      Regarding sexual function 20% reported impairment after surgery including
      dyspareunia in 14.5% (none preoperatively vs. eight postoperatively, <0.01) and
      loss of libido in 5.4%. CONCLUSION: The TVT procedure is an effective treatment
      for SUI. However, it can lead to postoperative voiding and sexual impairment.

PMID- 15453894
TI  - The prevalence of stress urinary incontinence among women operated on for
      abdominal wall hernias.
AB  - The high co-occurrence of an abdominal wall hernia (AWH) and stress urinary
      incontinence (SUI) suggests that there is a common factor in the etiopathogenesis
      of these disorders in these patients.

PMID- 15453895
TI  - Sexual function in women before and after suburethral sling operation for stress
      urinary incontinence: a retrospective questionnaire study.
AB  - BACKGROUND: The aim of this questionnaire study dealing with women with stress
      urinary incontinence was to find out what influence incontinence and operation
      for incontinence in the form of tension-free vaginal tape (TVT) or intravaginal
      slingplasty operation (IVS) had on the patient's sexuality and if there were any
      adverse effects on sexuality after the operation. METHODS: Eighty-four patients
      were operated on from April 1998 to September 2002. A questionnaire was sent to
      all patients with questions concerning their sexuality before and after the
      operation. RESULTS: Sixty-seven patients (81%) answered the questionnaire. Before
      the operation 53 patients (79%) were sexually active and 26 patients (49%)
      experienced incontinence during intercourse. Only one patient (0.01%) stated the
      incontinence as the reason for not being sexually active. No patients developed
      de novo incontinence during intercourse after the operation. Half of the patients
      who were cured of their incontinence during intercourse experienced a better
      sexual life. Five patients (7%) cited reduced libido after the operation and two
      patients (3%) felt the operation to be the cause. CONCLUSION: Among sexually
      active women with stress urinary incontinence referred for suburethral sling
      operation 49% experienced incontinence during intercourse and half of the cured
      patients in this group experienced a better sexual life after the operation.
      Incontinence affects sexual life to a great extend. Two patients (4%) experienced
      less libido after the operation and found the operation to be the cause of this.
      The risk of deterioration of sexual life after the operation is very small.
      Further investigation into this subject is needed.

PMID- 15453896
TI  - Reproducibility and validity of simple questions to identify urinary incontinence
      in elderly women.
AB  - BACKGROUND: Epidemiologic studies are dependent on simple and valid questions to
      assess the prevalence and type of urinary incontinence. OBJECTIVE: To examine the
      reproducibility and validity of two standardized questions seeking to identify
      stress and urge incontinence among elderly women. METHODS: A random sample of 421
      women 75 years or older living in the center of Odense, Denmark, were invited to
      participate, and 223 (53%) accepted a first interview in their home. A sample of
      154 women were selected for a second interview with the same questions [accepted
      by 144 (94%)]. The second visit also included a long open interview about
      incontinence and was followed by a prospective registration of leakages. RESULTS:
      In the first interview 39% (95% confidence interval (CI) 34-47%) of the elderly
      women reported incontinence. The reliability of the questions was acceptable
      [kappa of 0.81 (95% CI 0.34-0.89)] with percent agreement of 90% (95% CI 84-95%)
      between first and second interviews for all incontinence (stress and/or urge).
      When the open interview was used as a "gold standard," the questions showed
      acceptable validity: a sensitivity of 0.91 (95% CI 0.86-0.96) and a specificity
      of 0.86 (95% CI 0.80-0.92) for all incontinence. CONCLUSION: Standardized
      questions about incontinence give reproducible answers and produce information
      that is comparable to a long open interview.

PMID- 15453897
TI  - The effect of home biofeedback training on stress incontinence.
AB  - BACKGROUND: To compare the effectiveness of pelvic floor training (PFT) with the
      aid of a home biofeedback device to PFT alone for urodynamic stress urinary
      incontinence (SUI) in women after a 1-year follow-up. METHODS: A randomized study
      comparing two conservative interventions was conducted in an outpatient clinic of
      a university hospital. Thirty-five consecutive women were randomized to either
      the PFT with home biofeedback group or the PFT alone group. The intensive
      training period lasted 12 weeks. After 1 year, 33 women could be evaluated
      according to the protocol. At the 1-year visit pelvic floor muscle activity was
      measured and the need for surgical intervention was evaluated. Logistic
      multivariate analysis was used to predict response to the PFT. RESULTS: In the
      home biofeedback training group 11/16 (68.8%) avoided surgery vs. 10/19 (52.6%)
      in the PFT alone group. The difference was not statistically significant. In the
      nonoperated home biofeedback group the increase in pelvic floor muscle activity
      (p = 0.005 in supine, p = 0.005 in standing) and the decrease in leakage index (p
      = 0.05) was significant after 12 weeks and pelvic floor activity remained
      constant. By contrast, in the nonoperated PFT group the increase in pelvic floor
      muscle activity after 12 weeks predicted a good result for conservative
      treatment. CONCLUSIONS: This randomized controlled trial suggests that the home
      biofeedback method in PFT has a good success rate of 68.8%. The change achieved
      in leakage index after 12 weeks of training predicted an effective outcome for
      conservative treatment.

PMID- 15453898
TI  - Genetic and environmental influences on urinary incontinence: a Danish population
      based twin study of middle-aged and elderly women.
AB  - BACKGROUND: Familial clustering has been reported for urinary incontinence
      (stress and urge), but different etiologies for the two types of incontinence
      have been suggested. OBJECTIVE: The aim of this study was to estimate the
      relative influence of genetic and environmental factors on stress, urge, and
      mixed incontinence among elderly and middle-aged women. METHODS: This is a
      population-based classical twin study of 1168 female twin pairs [548 monozygotic
      (MZ) and 620 dizygotic (DZ)] from a middle-aged (46-68 years) and an old (70-94
      years) cohort identified in the Danish Twin Registry. Urinary incontinence was
      assessed with the help of two validated questions identifying stress and urge
      incontinence in interviews. RESULTS: For urge incontinence, the tetrachoric
      correlation was significantly higher for MZ twins, compared to that for DZ twin
      pairs in both middle-aged [0.51 (95% CI: 0.26-0.71) versus -0.22 (95% CI: -0.59
      0.18)] and elderly [0.50 (95% CI: 0.27-0.68) versus 0.28 (95% CI: 0.02-0.42)],
      indicating genetic effects. The heritability of urge incontinence was 42% (95%
      CI: 16-63%) among middle-aged women and 49% (95% CI: 29-65%) among the elderly.
      Moreover, mixed incontinence had a substantial genetic component. The role of
      genetic factors was less clear in stress incontinence. CONCLUSIONS: Genetic
      factors play a substantial role in the development of urge and mixed
      incontinence, whereas the role of genetic factors in stress incontinence is less
      prominent.

PMID- 15453899
TI  - The relationship between clinical parameters and health-related quality of life
      as measured by the 15D in incontinent women before and after treatment.
AB  - BACKGROUND: The purpose of this study was to correlate the clinical parameters
      with a health-related quality of life (HRQoL) measure and to describe the change
      of HRQoL caused by treatment and its modifying factors among urinary incontinent
      women. METHODS: Eighty-two incontinent women, referred to a tertiary gynecologic
      department, underwent clinical evaluation to establish diagnosis and severity of
      urinary incontinence (UI) and completed the generic 15D HRQoL instrument. Sixty
      nine women were re-evaluated 13 months after treatment. RESULTS: Compared to age
      matched female general population, the HRQoL of urinary incontinent women was
      significantly lower. Urge or mixed incontinence impairs HRQoL more than stress
      incontinence. The 15D scores correlated poorly with urodynamics, frequency/volume
      chart findings, and the amount of urine leakage. Among patients with stress UI
      (SUI), the HRQoL after treatment was the same as in the age-matched general
      female population. Among women with urge or mixed UI, the HRQoL improved
      significantly after treatment but did not reach the HRQoL level of women with SUI
      at baseline. In stepwise regression analysis, lower the 15D score at baseline and
      bigger the decrease in urine leakage, greater was the change in HRQoL for the
      better. CONCLUSION: There was a modest correlation of incontinence severity
      measures with quality of life impairment. The challenge for the future will be to
      improve the success of treatment for women with urge UI. The generic 15D appears
      to be sensitive to detect change in HRQoL due to treatment of UI women.

PMID- 15453900
TI  - Anal incontinence after obstetric sphincter tears: incidence in a Norwegian
      county.
AB  - BACKGROUND: Anal sphincter tears during vaginal delivery are a major cause of
      anal incontinence. We wanted to assess the incidence in a Norwegian county where
      primary repairs are performed in four hospitals using similar per- and
      postoperative protocol for the treatment of such injuries. METHODS: A postal
      questionnaire was distributed to all women who underwent primary repair of
      obstetric sphincter tears in the years 1999 and 2000 in the county of More and
      Romsdal. Symptoms of incontinence and fecal urgency were recorded. Incontinence
      was assessed using the Pescatori score system. RESULTS: Clinically detected
      sphincter tears occurred in 180 of 5123 vaginal deliveries (3.5%). The
      questionnaire was returned by 156 women (87%). Six women were excluded. Median
      follow-up was 25 months (range 4-39). Incontinence was reported by 88 women
      (59%), restricted to flatus incontinence in 53 cases (35%). Fecal urgency without
      incontinence was reported by 14 women (9%). Sixty-three women (42%) reported de
      novo moderate to severe symptoms. There was no difference in outcome whether the
      sphincter injury was partial or complete. Mean Pescatori score was 3.7 in women
      who felt disabled compared with 2.9 in women who did not feel disabled by their
      incontinence (P < 0.001). Of 29 women who felt disabled, only three had sought
      medical attention. Fifty-eight women (39%) had received no information about the
      sphincter tear before discharge. CONCLUSION: Anal incontinence is common after
      both partial and complete obstetric sphincter tears. Information before discharge
      is deficient, and women avoid seeking medical attention when incontinence
      develops.

PMID- 15453901
TI  - Clinical and histological safety assessment of rectocele repair using collagen
      mesh.
AB  - AIM: To clinically and histologically evaluate inflammatory response following
      rectocele repair using porcine collagen mesh. METHODS: Seventeen patients
      underwent rectocele repair using porcine collagen mesh. Inflammatory response was
      assessed by clinical and histological inflammatory grading pre- and
      postoperatively. Postoperative body temperature, complications and hospital stay
      was compared with 15 patients undergoing posterior colporraphy. RESULTS:
      Postoperative clinical examination did not demonstrate any inflammatory reaction.
      There were no significant changes in fibroblast count (P = 0.43), connective
      tissue density grading (P = 0.54), macrophage count (P = 0.20), inflammatory cell
      count (P = 0.48), total cell count (P = 0.51), or inflammatory grading (P = 0.87)
      postoperatively compared with preoperative values. Body temperature was
      significantly elevated for both the study and control group, although higher for
      the study group, postoperatively day 1 (P < 0.001). There were no significant
      differences in hospital stay and postoperative complications. CONCLUSION: Porcine
      collagen mesh was not associated with an adverse inflammatory response at
      clinical or histological evaluation and appears to be a safe material when used
      for rectocele repair.

PMID- 15453902
TI  - Peroperative bladder injury during hysterectomy for benign disorders.

PMID- 15453903
TI  - Urine culture at removal of indwelling catheter after elective gynecologic
      surgery: is it necessary?

PMID- 15453904
TI  - Treatment of recurrent genuine stress incontinence by shortening previously
      implanted tension-free vaginal tape.

PMID- 15453906
TI  - Hide and seek: the secret identity of the phosphatidylserine receptor.
AB  - Phosphatidylserine on the dying cell surface helps identify apoptotic cells to
      phagocytes, which then engulf them. A candidate phagocyte receptor for
      phosphatidylserine was identified using phage display, but the phenotypes of
      knockout mice lacking this presumptive receptor, as well as the location of the
      protein within cells, cast doubt on the assignment of this protein as the
      phosphatidylserine receptor.

PMID- 15453907
TI  - Isolation of suppressor genes that restore retrovirus susceptibility to a virus
      resistant cell line.
AB  - BACKGROUND: Genetic selections in mammalian cell lines have recently been
      developed for the isolation of mutant cells that are refractory to infection by
      retroviruses. These selections have been used to recover lines that block early
      postentry stages of infection, either before reverse transcription or before
      nuclear entry. The mechanisms of action of these blocks remain unknown. RESULTS:
      We have devised a method for the selection of genes from cDNA libraries that
      suppress the block to virus infection, and so restore virus susceptibility. The
      protocol involves the transformation of pools of resistant cells by cDNA
      expression libraries, followed by the selection for rare virus-sensitive cells,
      using multiple rounds of selection after infection by marked viral vector
      genomes. The suppressor genes were then recovered from these virus sensitive
      cells, and their ability to restore virus susceptibility was confirmed by
      reintroduction of these cDNAs into the resistant line. CONCLUSIONS: The
      identities of these genes provide insights into the mechanism of virus resistance
      and will help to define new pathways used during retrovirus infection. The
      methods for gene isolation developed here will also permit the identification of
      similar suppressors that modify or override other recently identified virus
      resistance genes.

PMID- 15453908
TI  - Chromosome loops arising from intrachromosomal tethering of telomeres occur at
      high frequency in G1 (non-cycling) mitotic cells: Implications for telomere
      capture.
AB  - BACKGROUND: To investigate potential mechanisms for telomere capture the spatial
      arrangement of telomeres and chromosomes was examined in G1 (non-cycling) mitotic
      cells with diploid or triploid genomes. This was examined firstly by directly
      labelling the respective short arm (p) and long arm subtelomeres (q) with
      different fluorophores and probing cell preparations using a number of
      subtelomere probe pairs, those for chromosomes 1, 3, 4, 5, 6, 7, 9, 10, 12, 17,
      18, and 20. In addition some interstitial probes (CEN15, PML and SNRPN on
      chromosome 15) and whole chromosome paint probes (e.g. WCP12) were jointly
      hybridised to investigate the co-localization of interphase chromosome domains
      and tethered subtelomeres. Cells were prepared by omitting exposure to colcemid
      and hypotonic treatments. RESULTS: In these cells a specific interphase
      chromosome topology was detected. It was shown that the p and q telomeres of the
      each chromosome associate frequently (80% pairing) in an intrachromosomal manner,
      i.e. looped chromosomes with homologues usually widely spaced within the nucleus.
      This p-q tethering of the telomeres from the one chromosome was observed with
      large (chromosomes 3, 4, 5), medium sized (6, 7, 9, 10, 12), or small chromosomes
      (17, 18, 20). When triploid nuclei were probed there were three tetherings of p-q
      subtelomere signals representing the three widely separated looped chromosome
      homologues. The separate subtelomere pairings were shown to coincide with
      separate chromosome domains as defined by the WCP and interstitial probes. The
      20% of apparently unpaired subtelomeric signals in diploid nuclei were partially
      documented to be pairings with the telomeres of other chromosomes. CONCLUSIONS: A
      topology for telomeres was detected where looped chromosome homologues were
      present at G1 interphase. These homologues were spatially arranged with respect
      to one-another independently of other chromosomes, i.e. there was no chromosome
      order on different sides of the cell nuclei and no segregation into haploid sets
      was detected. The normal function of this high frequency of intrachromosomal
      loops is unknown but a potential role is likely in the genesis of telomere
      captures whether of the intrachromosomal type or between non-homologues. This
      intrachromosomal tethering of telomeres cannot be related to telomeric or
      subtelomeric sequences since these are shared in varying degree with other
      chromosomes. In our view, these intrachromosomal telomeric tetherings with the
      resulting looped chromosomes arranged in a regular topology must be important to
      normal cell function since non-cycling cells in G1 are far from quiescent, are in
      fact metabolically active, and these cells represent the majority status since
      only a small proportion of cells are normally dividing.

PMID- 15453909
TI  - Effect of time of administration on cholesterol-lowering by psyllium: a
      randomized cross-over study in normocholesterolemic or slightly
      hypercholesterolemic subjects.
AB  - BACKGROUND: Reports of the use of psyllium, largely in hypercholesterolemic men,
      have suggested that it lowers serum cholesterol as a result of the binding of
      bile acids in the intestinal lumen. Widespread advertisements have claimed an
      association between the use of soluble fibre from psyllium seed husk and a
      reduced risk of coronary heart disease. Given the purported mechanism of
      cholesterol-lowering by psyllium, we hypothesized that there would be a greater
      effect when psyllium is taken with breakfast than when taken at bedtime.
      Secondarily, we expected to confirm a cholesterol-lowering effect of psyllium in
      subjects with "average" cholesterol levels. METHODS: Sixteen men and 47 women
      ranging in age from 18 to 77 years [mean 53 +/- 13] with LDL cholesterol levels
      that were normal or slightly elevated but acceptable for subjects at low risk of
      coronary artery disease were recruited from general gastroenterology and low risk
      lipid clinics. Following a one month dietary stabilization period, they received
      an average daily dose of 12.7 g of psyllium hydrophilic mucilloid, in randomized
      order, for 8 weeks in the morning and 8 weeks in the evening. Change from
      baseline was determined for serum total cholesterol, LDL, HDL and triglycerides.
      RESULTS: Total cholesterol for the "AM first" group at baseline, 8 and 16 weeks
      was 5.76, 5.77 and 5.80 mmol/L and for the "PM first" group the corresponding
      values were 5.47, 5.61 and 5.57 mmol/L. No effect on any lipid parameter was
      demonstrated for the group as a whole or in any sub-group analysis. CONCLUSION:
      The timing of psyllium administration had no effect on cholesterol-lowering and,
      in fact, no cholesterol-lowering was observed. Conclusions regarding the
      effectiveness of psyllium for the prevention of heart disease in the population
      at large may be premature.

PMID- 15453910
TI  - Dietary analysis and patterns of nutritional supplement use in normal and age
      related macular disease affected subjects: a prospective cross-sectional study.
AB  - BACKGROUND: Poor diet is thought to be a risk factor for many diseases, including
      age-related macular disease (ARMD), which is the leading cause of blind
      registration in those aged over 60 years in the developed world. The aims of this
      study were 1) to evaluate the dietary food intake of three subject groups:
      participants under the age of 50 years without ARMD (U50), participants over the
      age of 50 years without ARMD (O50), and participants with ARMD (AMD), and 2) to
      obtain information on nutritional supplement usage. METHODS: A prospective cross
      sectional study designed in a clinical practice setting. Seventy-four
      participants were divided into three groups: U50; 20 participants aged < 50
      years, from 21 to 40 (mean +/- SD, 37.7 +/- 10.1 years), O50; 27 participants
      aged > 50 years, from 52 to 77 (62.7 +/- 6.8 years), and ARMD; 27 participants
      aged > 50 years with ARMD, from 55 to 79 (66.0 +/- 5.8 years). Participants were
      issued with a three-day food diary, and were also asked to provide details of any
      daily nutritional supplements. The diaries were analysed using FoodBase 2000
      software. Data were input by one investigator and statistically analysed using
      Microsoft Excel for Microsoft Windows XP software, employing unpaired t-tests.
      RESULTS: Group O50 consumed significantly more vitamin C (t = 3.049, p = 0.005)
      and significantly more fibre (t = 2.107, p = 0.041) than group U50. Group ARMD
      consumed significantly more protein (t = 3.487, p = 0.001) and zinc (t = 2.252, p
      = 0.029) than group O50. The ARMD group consumed the highest percentage of
      specific ocular health supplements and the U50 group consumed the most
      multivitamins. CONCLUSIONS: We did not detect a deficiency of any specific
      nutrient in the diets of those with ARMD compared with age- and gender-matched
      controls. ARMD patients may be aware of research into use of nutritional
      supplementation to prevent progression of their condition.

PMID- 15453911
TI  - Using email reminders to engage physicians in an Internet-based CME intervention.
AB  - BACKGROUND: Engaging practicing physicians in educational strategies that
      reinforce guideline adoption and improve the quality of healthcare may be
      difficult. Push technologies such as email offer new opportunities to engage
      physicians in online educational reinforcing strategies. The objectives are to
      investigate 1) the effectiveness of email announcements in engaging recruited
      community-based primary care physicians in an online guideline reinforcement
      strategy designed to promote Chlamydia screening, 2) the characteristics of
      physicians who respond to email announcements, as well as 3) how quickly and when
      they respond to email announcements. METHODS: Over a 45-week period, 445
      recruited physicians received up to 33 email contacts announcing and reminding
      them of an online women's health guideline reinforcing CME activity.
      Participation was defined as physician log-on at least once to the website. Data
      were analyzed to determine participation, to compare characteristics of
      participants with recruited physicians who did not participate, and to determine
      at what point and when participants logged on. RESULTS: Of 445 recruited
      physicians with accurate email addresses, 47.2% logged on and completed at least
      one module. There were no significant differences by age, race, or specialty
      between participants and non-participants. Female physicians, US medical
      graduates and MDs had higher participation rates than male physicians,
      international medical graduates and DOs. Physicians with higher baseline
      screening rates were significantly more likely to log on to the course. The first
      10 emails were the most effective in engaging community-based physicians to
      complete the intervention. Physicians were more likely to log on in the afternoon
      and evening and on Monday or Thursday. CONCLUSIONS: Email course reminders may
      enhance recruitment of physicians to interventions designed to reinforce
      guideline adoption; physicians' response to email reminders may vary by gender,
      degree, and country of medical training. Repetition of email communications
      contributes to physician online participation.

PMID- 15453912
TI  - Randomised controlled trial of gabapentin in Complex Regional Pain Syndrome type
      1 [ISRCTN84121379].
AB  - BACKGROUND: Complex Regional Pain Syndrome type one (CRPS I) or formerly Reflex
      Sympathetic Dystrophy (RSD) is a disabling syndrome, in which a painful limb is
      accompanied by varying symptoms. Neuropathic pain is a prominent feature of CRPS
      I, and is often refractory to treatment. Since gabapentin is an anticonvulsant
      with a proven analgesic effect in various neuropathic pain syndromes, we sought
      to study the efficacy of the anticonvulsant gabapentin as treatment for pain in
      patients with CRPS I. METHODS: We did a randomized double blind placebo
      controlled crossover study with two three-weeks treatment periods with gabapentin
      and placebo separated by a two-weeks washout period. Patients started at random
      with gabapentin or placebo, which was administered in identical capsules three
      times daily. We included 58 patients with CRPS type 1. RESULTS: Patients reported
      significant pain relief in favor of gabapentin in the first period. Therapy
      effect in the second period was less; finally resulting in no significant effect
      combining results of both periods. The CRPS patients had sensory deficits at
      baseline. We found that this sensory deficit was significantly reversed in
      gabapentin users in comparison to placebo users. CONCLUSIONS: Gabapentin had a
      mild effect on pain in CRPS I. It significantly reduced the sensory deficit in
      the affected limb. A subpopulation of CRPS patients may benefit from gabapentin.

PMID- 15453913
TI  - Single nucleotide polymorphisms in the apolipoprotein B and low density
      lipoprotein receptor genes affect response to antihypertensive treatment.
AB  - BACKGROUND: Dyslipidemia has been associated with hypertension. The present study
      explored if polymorphisms in genes encoding proteins in lipid metabolism could be
      used as predictors for the individual response to antihypertensive treatment.
      METHODS: Ten single nucleotide polymorphisms (SNP) in genes related to lipid
      metabolism were analysed by a microarray based minisequencing system in DNA
      samples from ninety-seven hypertensive subjects randomised to treatment with
      either 150 mg of the angiotensin II type 1 receptor blocker irbesartan or 50 mg
      of the beta1-adrenergic receptor blocker atenolol for twelve weeks. RESULTS: The
      reduction in blood pressure was similar in both treatment groups. The SNP C711T
      in the apolipoprotein B gene was associated with the blood pressure response to
      irbesartan with an average reduction of 19 mmHg in the individuals carrying the C
      allele, but not to atenolol. The C16730T polymorphism in the low density
      lipoprotein receptor gene predicted the change in systolic blood pressure in the
      atenolol group with an average reduction of 14 mmHg in the individuals carrying
      the C-allele. CONCLUSIONS: Polymorphisms in genes encoding proteins in the lipid
      metabolism are associated with the response to antihypertensive treatment in a
      drug specific pattern. These results highlight the potential use of
      pharmacogenetics as a guide for individualised antihypertensive treatment, and
      also the role of lipids in blood pressure control.

PMID- 15453914
TI  - Microarrays for global expression constructed with a low redundancy set of 27,500
      sequenced cDNAs representing an array of developmental stages and physiological
      conditions of the soybean plant.
AB  - BACKGROUND: Microarrays are an important tool with which to examine coordinated
      gene expression. Soybean (Glycine max) is one of the most economically valuable
      crop species in the world food supply. In order to accelerate both gene discovery
      as well as hypothesis-driven research in soybean, global expression resources
      needed to be developed. The applications of microarray for determining patterns
      of expression in different tissues or during conditional treatments by dual
      labeling of the mRNAs are unlimited. In addition, discovery of the molecular
      basis of traits through examination of naturally occurring variation in hundreds
      of mutant lines could be enhanced by the construction and use of soybean cDNA
      microarrays. RESULTS: We report the construction and analysis of a low redundancy
      'unigene' set of 27,513 clones that represent a variety of soybean cDNA libraries
      made from a wide array of source tissue and organ systems, developmental stages,
      and stress or pathogen-challenged plants. The set was assembled from the 5'
      sequence data of the cDNA clones using cluster analysis programs. The selected
      clones were then physically reracked and sequenced at the 3' end. In order to
      increase gene discovery from immature cotyledon libraries that contain abundant
      mRNAs representing storage protein gene families, we utilized a high density
      filter normalization approach to preferentially select more weakly expressed
      cDNAs. All 27,513 cDNA inserts were amplified by polymerase chain reaction. The
      amplified products, along with some repetitively spotted control or 'choice'
      clones, were used to produce three 9,728-element microarrays that have been used
      to examine tissue specific gene expression and global expression in mutant
      isolines. CONCLUSIONS: Global expression studies will be greatly aided by the
      availability of the sequence-validated and low redundancy cDNA sets described in
      this report. These cDNAs and ESTs represent a wide array of developmental stages
      and physiological conditions of the soybean plant. We also demonstrate that the
      quality of the data from the soybean cDNA microarrays is sufficiently reliable to
      examine isogenic lines that differ with respect to a mutant phenotype and thereby
      to define a small list of candidate genes potentially encoding or modulated by
      the mutant phenotype.

PMID- 15453915
TI  - Strengths and weaknesses of EST-based prediction of tissue-specific alternative
      splicing.
AB  - BACKGROUND: Alternative splicing contributes significantly to the complexity of
      the human transcriptome and proteome. Computational prediction of alternative
      splice isoforms are usually based on EST sequences that also allow to approximate
      the expression pattern of the related transcripts. However, the limited number of
      tissues represented in the EST data as well as the different cDNA construction
      protocols may influence the predictive capacity of ESTs to unravel tissue
      specifically expressed transcripts. METHODS: We predict tissue and tumor specific
      splice isoforms based on the genomic mapping (SpliceNest) of the EST consensus
      sequences and library annotation provided in the GeneNest database. We further
      ascertain the potentially rare tissue specific transcripts as the ones
      represented only by ESTs derived from normalized libraries. A subset of the
      predicted tissue and tumor specific isoforms are then validated via RT-PCR
      experiments over a spectrum of 40 tissue types. RESULTS: Our strategy revealed
      427 genes with at least one tissue specific transcript as well as 1120 genes
      showing tumor specific isoforms. While our experimental evaluation of
      computationally predicted tissue-specific isoforms revealed a high success rate
      in confirming the expression of these isoforms in the respective tissue, the
      strategy frequently failed to detect the expected restricted expression pattern.
      The analysis of putative lowly expressed transcripts using normalized cDNA
      libraries suggests that our ability to detect tissue-specific isoforms strongly
      depends on the expression level of the respective transcript as well as on the
      sensitivity of the experimental methods. Especially splice isoforms predicted to
      be disease-specific tend to represent transcripts that are expressed in a set of
      healthy tissues rather than novel isoforms. CONCLUSIONS: We propose to combine
      the computational prediction of alternative splice isoforms with experimental
      validation for efficient delineation of an accurate set of tissue-specific
      transcripts.

PMID- 15453916
TI  - Long branch attraction, taxon sampling, and the earliest angiosperms: Amborella
      or monocots?
AB  - BACKGROUND: Numerous studies, using in aggregate some 28 genes, have achieved a
      consensus in recognizing three groups of plants, including Amborella, as
      comprising the basal-most grade of all other angiosperms. A major exception is
      the recent study by Goremykin et al. (2003; Mol. Biol. Evol. 20:1499-1505), whose
      analyses of 61 genes from 13 sequenced chloroplast genomes of land plants nearly
      always found 100% support for monocots as the deepest angiosperms relative to
      Amborella, Calycanthus, and eudicots. We hypothesized that this conflict reflects
      a misrooting of angiosperms resulting from inadequate taxon sampling,
      inappropriate phylogenetic methodology, and rapid evolution in the grass lineage
      used to represent monocots. RESULTS: We used two main approaches to test this
      hypothesis. First, we sequenced a large number of chloroplast genes from the
      monocot Acorus and added these plus previously sequenced Acorus genes to the
      Goremykin et al. (2003) dataset in order to explore the effects of altered
      monocot sampling under the same analytical conditions used in their study. With
      Acorus alone representing monocots, strongly supported Amborella-sister trees
      were obtained in all maximum likelihood and parsimony analyses, and in some
      distance-based analyses. Trees with both Acorus and grasses gave either a well
      supported Amborella-sister topology or else a highly unlikely topology with 100%
      support for grasses-sister and paraphyly of monocots (i.e., Acorus sister to
      "dicots" rather than to grasses). Second, we reanalyzed the Goremykin et al.
      (2003) dataset focusing on methods designed to account for rate heterogeneity.
      These analyses supported an Amborella-sister hypothesis, with bootstrap support
      values often conflicting strongly with cognate analyses performed without
      allowing for rate heterogeneity. In addition, we carried out a limited set of
      analyses that included the chloroplast genome of Nymphaea, whose position as a
      basal angiosperm was also, and very recently, challenged. CONCLUSIONS: These
      analyses show that Amborella (or Amborella plus Nymphaea), but not monocots, is
      the sister group of all other angiosperms among this limited set of taxa and that
      the grasses-sister topology is a long-branch-attraction artifact leading to
      incorrect rooting of angiosperms. These results highlight the danger of having
      lots of characters but too few and, especially, molecularly divergent taxa, a
      situation long recognized as potentially producing strongly misleading molecular
      trees. They also emphasize the importance in phylogenetic analysis of using
      appropriate evolutionary models.

PMID- 15453917
TI  - A population-based statistical approach identifies parameters characteristic of
      human microRNA-mRNA interactions.
AB  - BACKGROUND: MicroRNAs are approximately 17-24 nt. noncoding RNAs found in all
      eukaryotes that degrade messenger RNAs via RNA interference (if they bind in a
      perfect or near-perfect complementarity to the target mRNA), or arrest
      translation (if the binding is imperfect). Several microRNA targets have been
      identified in lower organisms, but only one mammalian microRNA target has yet
      been validated experimentally. RESULTS: We carried out a population-wide
      statistical analysis of how human microRNAs interact complementarily with human
      mRNAs, looking for characteristics that differ significantly as compared with
      scrambled control sequences. These characteristics were used to identify a set of
      71 outlier mRNAs unlikely to have been hit by chance. Unlike the case in C.
      elegans and Drosophila, many human microRNAs exhibited long exact matches (10 or
      more bases in a row), up to and including perfect target complementarity. Human
      microRNAs hit outlier mRNAs within the protein coding region about 2/3 of the
      time. And, the stretches of perfect complementarity within microRNA hits onto
      outlier mRNAs were not biased near the 5'-end of the microRNA. In several cases,
      an individual microRNA hit multiple mRNAs that belonged to the same functional
      class. CONCLUSIONS: The analysis supports the notion that sequence
      complementarity is the basis by which microRNAs recognize their biological
      targets, but raises the possibility that human microRNA-mRNA target interactions
      follow different rules than have been previously characterized in Drosophila and
      C. elegans.

PMID- 15453918
TI  - cuticleDB: a relational database of Arthropod cuticular proteins.
AB  - BACKGROUND: The insect exoskeleton or cuticle is a bi-partite composite of
      proteins and chitin that provides protective, skeletal and structural functions.
      Little information is available about the molecular structure of this important
      complex that exhibits a helicoidal architecture. Scores of sequences of cuticular
      proteins have been obtained from direct protein sequencing, from cDNAs, and from
      genomic analyses. Most of these cuticular protein sequences contain motifs found
      only in arthropod proteins. DESCRIPTION: cuticleDB is a relational database
      containing all structural proteins of Arthropod cuticle identified to date. Many
      come from direct sequencing of proteins isolated from cuticle and from sequences
      from cDNAs that share common features with these authentic cuticular proteins. It
      also includes proteins from the Drosophila melanogaster and the Anopheles gambiae
      genomes, that have been predicted to be cuticular proteins, based on a Pfam motif
      (PF00379) responsible for chitin binding in Arthropod cuticle. The total number
      of the database entries is 445: 370 derive from insects, 60 from Crustacea and 15
      from Chelicerata. The database can be accessed from our web server at
      http://bioinformatics.biol.uoa.gr/cuticleDB. CONCLUSIONS: CuticleDB was primarily
      designed to contain correct and full annotation of cuticular protein data. The
      database will be of help to future genome annotators. Users will be able to test
      hypotheses for the existence of known and also of yet unknown motifs in cuticular
      proteins. An analysis of motifs may contribute to understanding how proteins
      contribute to the physical properties of cuticle as well as to the precise nature
      of their interaction with chitin.

PMID- 15453919
TI  - Few amino acid positions in rpoB are associated with most of the rifampin
      resistance in Mycobacterium tuberculosis.
AB  - BACKGROUND: Mutations in rpoB, the gene encoding the beta subunit of DNA
      dependent RNA polymerase, are associated with rifampin resistance in
      Mycobacterium tuberculosis. Several studies have been conducted where minimum
      inhibitory concentration (MIC, which is defined as the minimum concentration of
      the antibiotic in a given culture medium below which bacterial growth is not
      inhibited) of rifampin has been measured and partial DNA sequences have been
      determined for rpoB in different isolates of M. tuberculosis. However, no model
      has been constructed to predict rifampin resistance based on sequence information
      alone. Such a model might provide the basis for quantifying rifampin resistance
      status based exclusively on DNA sequence data and thus eliminate the requirements
      for time consuming culturing and antibiotic testing of clinical isolates.
      RESULTS: Sequence data for amino acid positions 511-533 of rpoB and associated
      MIC of rifampin for different isolates of M. tuberculosis were taken from studies
      examining rifampin resistance in clinical samples from New York City and
      throughout Japan. We used tree-based statistical methods and random forests to
      generate models of the relationships between rpoB amino acid sequence and
      rifampin resistance. The proportion of variance explained by a relatively simple
      tree-based cross-validated regression model involving two amino acid positions
      (526 and 531) is 0.679. The first partition in the data, based on position 531,
      results in groups that differ one hundredfold in mean MIC (1.596 micrograms/ml
      and 159.676 micrograms/ml). The subsequent partition based on position 526, the
      most variable in this region, results in a > 354-fold difference in MIC. When
      considered as a classification problem (susceptible or resistant), a cross
      validated tree-based model correctly classified most (0.884) of the observations
      and was very similar to the regression model. Random forest analysis of the MIC
      data as a continuous variable, a regression problem, produced a model that
      explained 0.861 of the variance. The random forest analysis of the MIC data as
      discrete classes produced a model that correctly classified 0.942 of the
      observations with sensitivity of 0.958 and specificity of 0.885. CONCLUSIONS:
      Highly accurate regression and classification models of rifampin resistance can
      be made based on this short sequence region. Models may be better with improved
      (and consistent) measurements of MIC and more sequence data.

PMID- 15453920
TI  - 40th Annual Meeting of the American Society of Clinical Oncology June 2004 New
      Orleans, Louisiana.

PMID- 15453921
TI  - Rituximab Improves Rate and Duration of Chemotherapy-Induced Remissions in
      Indolent and Aggressive Non-Hodgkin's Lymphoma.

PMID- 15453922
TI  - The impact of conventional and high-dose therapy for lymphoma on fertility.
AB  - The impact of chemotherapy on gonadal function is an important issue for younger
      patients surviving lymphoma. This article reviews the effects on fertility of
      conventional and intensive-dose chemotherapy regimens with or without radiation
      therapy. In general, conventional dose regimens such as ABVD
      (doxorubicin/bleomycin/vinblastine/decarbazine) and CHOP21
      (cyclophosphamide/doxorubicin/vincristine/prednisone) are not sterilizing, but
      data are limited on the effects of newer aggressive regimens such as BEACOPP
      (bleomycin/etoposide/doxorubicin/cyclophosphamide/vincristine/procarbazine/predni
      one), CHOP14, and CHOP/etoposide. Infertility after myeloablative transplant
      conditioning is common but not invariable. The role of prechemotherapy
      gonadotrophin-releasing hormone agonists and antagonists for the prevention of
      gonadal damage is under evaluation. In addition, new techniques for sperm and
      oocyte retrieval offer the prospect of improved fertility after sterilizing
      treatment. Management guidelines for patients undergoing nonmyeloblative and
      myeloablative therapy are presented, addressing additional issues such as
      contraception during and after the administration of cytotoxics and the
      importance of gynecologic and endocrine follow-up in determining the need for
      short- and long-term hormone replacement therapy.

PMID- 15453923
TI  - Pathology of primary cutaneous B-cell lymphomas: diagnosis and classification.
AB  - The skin is the second most common extranodal site for non-Hodgkin's lymphomas.
      Therefore, hematologists, pathologists, and dermatologists need to be familiar
      with these lymphomas. Primary cutaneous B-cell lymphomas are less common than T
      cell lymphomas but have received much attention in the past few years. Their
      typical clinical and pathologic features are becoming clear. However, there is
      still some disagreement in terminology and characteristics of these lymphomas
      between the World Heath Organization (WHO) classification and the European
      Organisation for Research and Treatment of Cancer (EORTC) proposal for primary
      cutaneous lymphomas. This review will focus on the features of primary cutaneous
      B-cell lymphomas, compare and contrast areas of discordance between the WHO and
      EORTC systems, and outline areas for further investigation.

PMID- 15453924
TI  - Yttrium 90-labeled ibritumomab tiuxetan radioimmunotherapy produces high response
      rates and durable remissions in patients with previously treated B-cell lymphoma.
AB  - We report updated time-to-event variables of a phase III randomized study
      comparing yttrium 90-labeled ibritumomab with rituximab standard therapy in 143
      rituximab-naive patients with relapsed or refractory low-grade, follicular, or
      transformed CD20+ non-Hodgkin's lymphoma (NHL). Most patients (79%) had
      follicular lymphoma. Patients were randomized to receive a single intravenous
      (I.V.) dose of 90Y ibritumomab tiuxetan 0.4 mCi/kg (n = 73) or rituximab 375
      mg/m2 I.V. weekly for 4 doses (n = 70). The radioimmunotherapy group was
      pretreated with 2 rituximab doses (250 mg/m2) to improve biodistribution and one
      dose of Indium 111-labeled ibritumomab tiuxetan for imaging. The overall response
      rate was 80% versus 56% (P = 0.002) and complete response (CR)/CR unconfirmed
      (CRu) rates were 34% for 90Y ibritumomab tiuxetan versus 20% for rituximab. With
      a median follow-up of 44 months, the data are mature as all ongoing patients in
      both groups exceeded the median Kaplan-Meier estimated time to progression (TTP),
      duration of response (DR), and time to next therapy. Although this study was not
      powered to detect differences in time-to-event variables, the results from this
      randomized trial demonstrate trends toward longer median TTP (15 vs. 10.2 months;
      P = 0.07), DR (16.7 vs. 11.2 months; P = 0.44) and time to next therapy (21.1 vs.
      13.8 months; P = 0.27) in follicular NHL patients treated with 90Y ibritumomab
      tiuxetan compared with the rituximab control arm. In patients achieving a CR/CRu,
      the median TTP was 24.7 months for patients treated with 90Y ibritumomab tiuxetan
      compared with 13.2 months for rituximab-treated patients (P = 0.41), and ongoing
      responses of > 5 years have been observed. These results confirm that 90Y
      ibritumomab tiuxetan produces high response rates and durable remissions in
      patients with previously treated low-grade, follicular, and transformed NHL.

PMID- 15453925
TI  - Progress in the prognosis of adult Hodgkin's lymphoma in the past 35 years
      through clinical trials in Argentina: a GATLA experience.
AB  - The purpose of this study was to evaluate the trends in complete remission (CR)
      rate, disease-free survival (DFS), and overall survival (OS) through 35 years of
      Grupo Argentino de Tratamiento de la Leucemia Aguda (GATLA) clinical trials. A
      total of 1,254 adult patients with Hodgkin's Lymphoma were evaluated according to
      seven consecutive protocols. This 35-year study was divided into three phases.
      The patients in the first phase (1968-1985) were treated with CVPP
      (cyclophosphamide/vinblastine/procarbazine/prednisone) plus involved-field
      radiotherapy (IFRT). In the CVPP regimen, cyclophosphamide and vinblastine were
      administered intravenously on day 1 and prednisone and procarbazine were
      administered orally on days 1-14 every 28 days. The second phase (1986-1996) used
      mainly reinforced CVPP with cyclophosphamide and vinblastine on days 1-8 plus
      IFRT. The third phase (1997-2003) used
      ABVD(doxorubicin/bleomycin/vinblastine/dacarbazine) plus IFRT. In clinical stage
      I/II, the CR rate was 86% in 252 patients treated in the first phase and DFS and
      OS were 57% and 78% at 5 years and 50% and 71% at 10 years. The second phase had
      148 patients with clinical stage I/II disease, and the CR rate was 91%, 5-year
      DFS and OS were 78% and 90%, and 10-year DFS and OS were 70% and 83%. The third
      phase had 182 patients with clinical stage I/II disease, and the CR rate was 95%,
      5-year DFS and OS were 87% and 96%, and 10-year DFS and OS were not reached. The
      statistical difference was P = 0.016 in terms of CR and P < 0.001 in terms of DFS
      and OS. In the first phase of 394 patients with clinical stage III/IV disease,
      the CR rate was 71%, DFS and OS at 5 years were 37% and 62%, and DFS and OS at 10
      years were 32% and 53%. In the second phase of 164 patients with clinical stage
      III/IV disease, the CR rate was 84%, DFS and OS at 5 years were 66% and 80%, and
      DFS and OS at 10 years were 60% and 75%. In the third phase of 114 patients with
      clinical stage III/IV disease, the CR rate was 88% and DFS and OS at 5 years were
      60% and 90%. The DFS and OS were not reached at 10 years. The differences among
      the 3 phases in CR, DFS and OS were highly significant (P < 0.001).

PMID- 15453926
TI  - Results of a phase II multicenter trial of single-agent gemcitabine in patients
      with relapsed or chemotherapy-refractory Hodgkin's lymphoma.
AB  - This study's objective was to determine the efficacy and safety of gemcitabine in
      patients with relapsed or chemotherapy-refractory Hodgkin's lymphoma (HL). Twenty
      nine patients were enrolled. Eight of the first 10 patients received intravenous
      gemcitabine (1250 mg/m2) days 1, 8, and 15 every 4 weeks. Two patients withdrew
      consent before treatment. Because of toxicity, the remaining 19 patients received
      1000 mg/m2 on days 1 and 8 every 3 weeks. Of the 29 treated patients, 16 (55.2%)
      were male, the median age was 43 years (range, 20.9-77.3), and 89.7% of them were
      white. Twelve patients (41.4%) had an Eastern Cooperative Oncology Group
      performance status (PS) of 0, 14 (48.3%) had a PS of 1, and 3 (10.3%) had a PS of
      2. All patients had >/= 2 prior chemotherapy regimens. Eighteen patients (62%)
      had a relapse following bone marrow transplantation. Of 27 evaluable patients, 6
      (22%) had partial response, 14 (52%) had stable disease, and 7 (26%) had
      progressive disease. The median time to progression for all patients was 6.4
      months (range, 1.1-21.9). The median survival for all patients was 26.9 months
      (range, < 1-28.4). All patients have discontinued treatment because of disease
      progression or relapse. Grade >/= 3 toxicity occurred in 14 patients (48.3%):
      thrombocytopenia (33.3%), neutropenia (29.6%), anemia (7.4%), increased alanine
      aminotransferase, reduced cardiac function, and fever (3.7% for each event). This
      study confirms the activity of gemcitabine in relapsed and highly refractory HL.
      Dose and schedule may be modified in the future to optimize responses. As
      gemcitabine is active in highly refractory/relapsed HL, future studies should
      consider incorporating gemcitabine in combination regimens as first-line therapy
      for patients with high-risk HL.

PMID- 15453927
TI  - Dose-intense cyclophosphamide and etoposide for patients with refractory or high
      risk non-Hodgkin's lymphoma.
AB  - A retrospective review was performed on the toxicity and response to one cycle of
      dose-intense cyclophosphamide/etoposide, followed by consolidation in patients
      with refractory or previously untreated, high-risk non-Hodgkin's lymphoma (NHL).
      Fifty-five patients with refractory NHL and 13 with untreated, high-risk NHL were
      administered one cycle of daily cyclophosphamide 1.5 g/m2 intravenously on days 1
      4 and etoposide 300 mg/m2 intravenously every 12 hours on days 1-3. Responders
      then received other consolidated regimens. Twenty-seven percent of patients with
      refractory disease had moderate or severe stomatitis, and 44% had moderate or
      severe infections with 6 (11%) dying of this complication. Similar complication
      rates were noted in the previously untreated, high-risk group, but there was no
      treatment-related mortality. The overall response rate to this one cycle of
      therapy was 31% in the refractory group, with 18% complete response and 13%
      partial response. The overall response rate in the previously untreated, high
      risk group was 69%, with 54% complete and 15% partial responses. In responders,
      the 2-year event-free survival was 27% in the refractory group and 56% in high
      risk group. Dose-intense cyclophosphamide/etoposide has promising efficacy;
      however, nonhematologic toxicity can be considerable. The better tolerance, high
      response rate, and encouraging 2-year survival of this regimen in combination
      with further dose-dense consolidation in patients with high-risk NHL are
      encouraging.

PMID- 15453928
TI  - Mutational status of IgVH genes consistent with antigen-driven selection but not
      percent of mutations has prognostic impact in B-cell chronic lymphocytic
      leukemia.
AB  - Mutational status of immunoglobulin heavy-chain variable-region (IgVH) genes,
      along with CD38 expression, is a prognostic marker in B-cell chronic lymphocytic
      leukemia (B-CLL). Configuration of IgVH genes displaying > 2% mismatch has been
      shown to correlate with longer survivals. In a series of 64 B-CLLs, we failed to
      confirm the prognostic value of the IgVH gene mutational status by using the
      suggested cutoff. However, the IgVH mutational status maintained its prognostic
      value only when evidence of antigen-driven selection could be documented. This
      was accomplished by applying statistical methods aimed at evaluating a
      significant skewing of replacement mutations from framework to complementary
      determining regions, as it occurs during germinal center differentiation of B
      cells. These data caution against wide application of the 2% somatic mutation
      cutoff as a prognostic determinant without demonstration of antigen-driven
      selection.

PMID- 15453929
TI  - Can[18F] fluorodeoxyglucose positron emission tomography replace bone marrow
      biopsy in staging of malignant lymphoma?

PMID- 15453930
TI  - Non-Hodgkin's lymphoma in the microarray era.

PMID- 15453931
TI  - A prospective, open-label safety and efficacy study of combination treatment with
      melphalan, arsenic trioxide, and ascorbic acid in patients with relapsed or
      refractory multiple myeloma.

PMID- 15453932
TI  - Is it useful to divide level VA of the neck into two sections?

PMID- 15453933
TI  - Garnett Passe and Rodney Williams Memorial Lecture: New clinical tests of
      unilateral vestibular dysfunction.
AB  - Vertigo is caused by unilateral vestibular dysfunction. Unilateral vestibular
      dysfunction represents either vestibular overactivity as benign positional
      vertigo or underactivity as in labyrinthitis or both, at different times, as in a
      Meniere's attack. Unilateral dysfunction could also be central rather than
      peripheral, such as in a lateral medullary syndrome. Unilateral vestibular
      dysfunction could affect any of the five different sensory areas in the
      labyrinth, the three semicircular canals and the two otoliths, or their brainstem
      connections. For rigorous diagnosis of the cause of vertigo, ideally one would
      have robust, reproducible, quantitative vestibular function tests sensitive to
      dysfunction of each of the five sensory regions in each ear. In working towards
      this ideal we have, over the last 15 years, developed three new vestibular
      function tests: (1) impulsive tests of individual semicircular canal function,
      (2) evoked potential tests of saccular function and (3) subjective visual
      horizontal tests of utricular function. The physiological rationale of these
      three tests is reviewed as well as the interpretation of their results in various
      diseases.

PMID- 15453934
TI  - Endoscopic stapling of pharyngeal pouch.
AB  - The relatively new technique of endoscopic stapling in the surgical management of
      pharyngeal pouch has gained widespread popularity over the last few years. The
      technique seems to be the procedure of choice as it is easier and quicker to
      perform and has a lower morbidity compared with open techniques. We present here
      an overview of the current evidence provided by a literature search performed by
      Ovid MEDLINE on literature published between January 1993 and May 2003 on
      endoscopic stapling of pharyngeal pouch. Several case series have been reported
      on various aspects of the surgery. The modifications in technique, peri-operative
      care, success rate, complications and recurrence are summarized, based on
      observational analytical case series. There were no randomized controlled trials
      comparing this approach to any other endoscopic or open surgical techniques for
      pharyngeal pouch.

PMID- 15453935
TI  - Canalplasty for severe external auditory meatus exostoses.
AB  - Exostoses of the external auditory meatus is a well known condition which
      infrequently requires surgical correction. However, the stenosis caused by severe
      exostosis can affect quality of life considerably and may require surgical
      intervention. Canalplasty, in such a situation, is a valid and effective
      management option. In our series the commonest indication for surgery was
      recurrent otitis externa. The detailed surgical technique is described and a
      retrospective analysis of 65 such procedures is presented. There were only two
      significant complications, both post-operative stenosis, requiring further
      corrective surgery. In conclusion, canalplasty for the exostosis of the external
      auditory meatus is a safe surgical option.

PMID- 15453936
TI  - Long-term outcome of modified radical mastoidectomy.
AB  - The primary aim of treatment of cholesteatoma is to attain a dry, safe, stable
      ear, free of disease. Maintaining or improving hearing is important but the
      pursuit of a hearing result should not compromise this primary aim. This study
      reviews the long-term outcome of 133 patients, suffering from advanced disease,
      who underwent modified radical mastoidectomy between 1995 and 2000. Of these, 49
      per cent had had previous mastoid surgery elsewhere. A dry, waterproof ear was
      attained in 95 per cent of patients. In 77 per cent of patients, hearing was
      unchanged or improved. In this period, there were two cases of significant post
      operative loss in bone conduction, including one dead ear secondary to
      suppurative labyrinthitis. There were epithelial pearls on follow up in two per
      cent. These results indicate that when properly performed, modified radical
      mastoidectomy provides safe surgical access and clears disease with low
      recurrence rates while mostly maintaining or improving hearing.

PMID- 15453937
TI  - Association between osteoporosis and otosclerosis in women.
AB  - Similarities between osteoporosis and otosclerosis have been noted, including a
      similar association with the COL1A1 gene. Herein, the authors explore the
      possible clinical relationship between these two common disorders of bone. In
      this retrospective study, the medical charts of 100 women aged 50 through 75
      years who had undergone stapedectomy for otosclerosis were reviewed and the
      prevalence of osteoporosis in these women was noted. Similarly, the prevalence of
      osteoporosis was determined in a control group of 100 women aged 50 to 75 years
      with presbycusis. Fifteen of 100 women with otosclerosis had a concomitant
      diagnosis of osteoporosis as compared with four of 100 women with presbycusis,
      yielding a significant clinical association (p = 0.007) between otosclerosis and
      osteoporosis. This study suggests an association between otosclerosis and
      osteoporosis, providing impetus and justification for future prospective clinical
      studies and related research.

PMID- 15453938
TI  - Increasing annual incidence of vestibular schwannoma and age at diagnosis.
AB  - During the last 26 years the annual number of diagnosed vestibular schwannomas
      (VS) has been increasing. The aim of this study is to describe and analyse this
      increase. Since 1976, 1446 new cases of VS have been diagnosed at the authors'
      centre. Special focus was on the age at diagnosis, the localization and the size
      of the tumour. The size of the tumour was registered as either intrameatal or
      with the largest extrameatal diameter. The annual number of diagnosed VS has
      increased from 26 in 1976 to 101 in 2001. The size of the diagnosed tumours has
      decreased from a median of 35 mm in 1979 to 10 mm in 2001. In the first years
      large and giant tumours dominated, in contrast to recent years in which
      intrameatal and small tumours dominated. The median age at the time of diagnosis
      has been almost unchanged through the period (median 55 years). If the decreasing
      size of the tumour and the increasing incidence of VS can be explained only by
      earlier diagnosis and easier access to magnetic resonance (MR) scanning it should
      be expected that the median age at the time of diagnosis would decrease
      simultaneously. In this study, the median age at the time of diagnosis has been
      almost unchanged throughout the 26-year period. This paradox can be explained by
      the fact that, with easier access to MR scanning, the examination has been
      offered also to elderly patients, in whom the small and intrameatal tumours
      dominate.

PMID- 15453939
TI  - Endoscopic dacrocystorhinostomy: long-term results and evolution of surgical
      technique.
AB  - This study evaluated the long-term results of endoscopic dacrocystorhinostomy
      (DCR) performed as a day-case procedure under local anaesthesia. It assessed the
      patient satisfaction with the procedure by retrospective review and a
      questionnaire survey. Seventy patients were referred for endoscopic DCR to the
      senior author between 1997 and 2000. A success rate of 92 per cent was achieved
      at three months and it was possible to perform 85 per cent of cases under local
      anaesthetic; 91 per cent were discharged on the same day. Long-term follow up by
      postal survey revealed that the watering eye had improved following surgery in 83
      per cent (follow up range = eight to 66 months; mean = 28.6 months). Eighty-eight
      per cent were satisfied with the tolerability of the procedure under local
      anaesthesia. The authors describe changes in technique, which evolved with their
      experience of the procedure. Endoscopic dacrocystorhinostomy can be performed
      safely and successfully as a day-case procedure under local anaesthesia with
      excellent results and with great satisfaction to the patients.

PMID- 15453940
TI  - Detection of laryngeal carcinoma and epithelial hyperplastic laryngeal lesions
      via a rapid-access dysphonia clinic.
AB  - Recent government initiatives in the UK have focused on streamlining oncology
      services by reducing waiting times between urgent referral, assessment and
      treatment of patients with possible cancer. The performance of the Quick Early
      Diagnosis Dysphonia Clinic of the Queen Elizabeth Hospital, Birmingham, between
      May 1997 and April 2001 was reviewed. Of 721 patients reviewed, 123 (17 per cent)
      had clinically suspicious laryngeal lesions. Thirteen cases of epithelial
      hyperplastic laryngeal lesions and 27 laryngeal malignancies were diagnosed.
      There was no statistical link between early cancer detection and assessment
      within two weeks of referral. However, rapid-access clinics for dysphonia serve
      an important role in the reassurance and multidisciplinary management of patients
      with persistent hoarseness. Greater financial commitments are necessary to
      achieve compliance with objectives for a maximum two-week wait for patients with
      suspected laryngeal malignancy.

PMID- 15453941
TI  - Frontal sinus obliteration.
AB  - This article highlights the indications for frontal sinus obliteration and
      suggests some intra-operative points to aid the surgeon in performing the
      operative procedure. It also reiterates the three principal points that need to
      be followed. There must be: (1) Meticulous removal of all visible mucosa and the
      inner bony cortex of the sinus wall. (2) Permanent occlusion of the nasofrontal
      duct. (3) The correct choice of material for the obliteration.

PMID- 15453942
TI  - Granuloma annulare presenting as multiple nodules on the pinna.
AB  - Granuloma annulare is a benign, idiopathic, inflammatory dermatosis characterized
      clinically by dermal papules and annular plaques. We describe the case of a 40
      year-old man who presented with a long history of multiple nodules on the left
      pinna. Histological examination revealed the typical necrobiotic granulomas of
      granuloma annulare. The condition predominantly affects the extremities of
      children and young adults; cases involving the pinna are extremely rare. Nodular
      lesions are common in otolaryngological practice, and this case illustrates the
      need for careful clinical assessment and appropriate biopsy in diagnosing lesions
      of the outer ear

PMID- 15453943
TI  - Bony overgrowth onto fixture component of a bone-anchored hearing aid.
AB  - An eight-year-old boy with Treacher Collins syndrome was fitted with a bone
      anchored hearing aid. The audiometric result was excellent. Two years later, the
      abutment began to loosen and could not be tightened. It was thought that a new
      fixture would be required, with loss of use of the aid for three months. At
      surgery, bone was found to be growing over the hexagonal joint between fixture
      and abutment. A simple and rapid solution to this problem is described.

PMID- 15453944
TI  - Topical vancomycin for chronic suppurative otitis media with methicillin
      resistant Staphylococcus aureus otorrhoea.
AB  - There has been a steady increase in the number of cases of methicillin-resistant
      Staphylococcus aureus (MRSA) otorrhoea; this is a growing concern. The purpose of
      this study was to evaluate the efficacy of topical vancomycin treatment in
      patients with MRSA otorrhoea. Fifty-five patients with MRSA otorrhoea were
      prospectively enrolled into the study. Thirty-five patients were treated with
      vancomycin eardrops as outpatients. The concentration of the locally prepared
      vancomycin solution was 25 mg/ml. The dose of vancomycin was two drops three
      times daily for 10 days. As a control group, 20 patients were treated with
      gentamicin 0.3% solution. Data were analysed by the Mann-Whitney U test to
      compare the efficacy of vancomycin eardrops and gentamicin eardrops. In the
      vancomycin group, the otorrhoea was significantly reduced in 33 ears (94%); in
      the gentamicin group, in four ears (20 per cent); this reduction was
      statistically significant (P < 0.03). The use of topical vancomycin treatment was
      effective for patients with MRSA otorrhoea refractory to conventional antibiotic
      treatment.

PMID- 15453945
TI  - Laryngeal cleft type I: a novel method of repair using Bioplastique.
AB  - The authors report a novel treatment of a case of type I laryngeal cleft
      diagnosed in an adult. They describe a technique of endoscopic obliteration of
      the posterior commissure defect. Initially, a test implant of starch and
      adrenaline was used, followed by permanent staged injections of Bioplastique to
      the posterior commissure. This rare congenital anomaly usually presents in
      childhood but late presentation should be considered when adults present with
      lifelong dysphonia especially when associated with gastro-oesophageal reflux
      disease.

PMID- 15453946
TI  - Exceptionally elevated creatine kinase levels in a laryngectomized patient:
      hypothyroid myopathy.
AB  - We present a laryngectomized patient with unspecific complaints of fatigue whose
      laboratory findings were out of proportion with the clinical presentation. The
      enormously high blood levels of creatine kinase (CPK) (8000 IU/l, normal range 30
      190 IU/l) and thyroid-stimulating hormone (100 mU/l, normal range 0.5-4.5 mU/l)
      led to diagnosis and treatment of and recovery from hypothyroid myopathy.
      Hypothyroidism reduces the ability of the muscle to maintain its adequate
      energetic economy, via several suggested mechanisms. This may lead to injury
      (myopathy) that allows enzymes such as CPK to leak out of cells and causes
      elevation of their serum levels. To our knowledge, this is the first reported
      case of a patient previously treated for head and neck cancer who developed
      hypothyroid myopathy, presenting with exceptionally elevated CPK levels. This is
      noteworthy, since hypothyroidism may be easily avoided by a comprehensive follow
      up of patients treated for head and neck cancer.

PMID- 15453947
TI  - Somatostatin analogues have no role in the treatment of advanced differentiated
      thyroid cancer.
AB  - Somatostatins are neuropeptides that have a downregulatory effect on various
      physiological processes. Their use in the management of certain endocrine tumours
      is well recognized. Their use in thyroid cancer is not established, although
      there is some evidence to suggest that they have a role in advanced metastatic
      disease. We report a case of a patient with advanced metastatic follicular
      thyroid cancer which demonstrated strong octreotide uptake with reduced avidity
      for I(131). Treatment with the somatostatin analogue octreotide, however, failed
      to achieve a significant response. We feel this case is important as it suggests
      that although octreotide provides a useful further imaging modality in
      differentiated thyroid cancer, it has no therapeutic role.

PMID- 15453948
TI  - Tracheal haemangioma: case report.
AB  - A case of lobular capillary haemangioma of the trachea is presented. The patient
      gave a history of foreign body sensation in the throat and multiple episodes of
      haemoptysis. The chest X-ray was normal. A spiral computed tomograph (CT) with
      three-dimensional reconstruction revealed a small tracheal mass in the antero
      lateral wall of the trachea, which was excised by endoscopy. The
      histopathological diagnosis was lobular capillary haemangioma, a rare, benign
      tumour of the trachea. A high index of suspicion with the spiral CT finding was
      responsible for early diagnosis of the tumour.

PMID- 15453949
TI  - Total necrosis of tongue due to severe haemorrhage.

PMID- 15453950
TI  - A novel method for replacement of a blocked fine-bore nasogastric tube.

PMID- 15453951
TI  - Type of drug abuse in patients with psychogenic cough.

PMID- 15453953
TI  - Alemtuzumab in peripheral T-cell malignancies.
AB  - The humanized monoclonal antibody CAMPATH-1H (alemtuzumab) binds to the CD52
      antigen, a glycoprotein that is widely expressed on normal and malignant B- and T
      lymphocytes. Over the past 5 years, a number of trials have demonstrated that
      alemtuzumab has clinical activity in mature T-cell diseases such as T-cell
      prolymphocytic leukemia (T-PLL) and cutaneous T-cell lymphoma (CTCL). In heavily
      pretreated relapsed/refractory patients alemtuzumab induced responses in more
      than two thirds of T-PLL and more than 50% of CTCL patients. Responding patients
      had improved survival compared to nonresponders. Alemtuzumab is particularly
      effective in clearing malignant lymphocytes from peripheral blood and bone marrow
      and may therefore facilitate stem-cell transplantation (SCT) in selected
      patients. The toxicity profile for the antibody is acceptable; the major
      complications are infusional reactions, which generally subside after the first 1
      2 weeks of therapy, and prolonged lymphopenia associated with reactivation of
      viruses. These can be minimized by careful monitoring and the use of prophylactic
      therapy. Future studies will be directed toward: alternative routes
      (subcutaneous) and schedules of administration; use as first-line therapy;
      combination strategies with conventional chemotherapy; and use of alemtuzumab to
      purge minimal residual bone-marrow disease prior to SCT.

PMID- 15453954
TI  - Improved tumor targeting of radiolabeled RGD peptides using rapid dose
      fractionation.
AB  - Arginine-glycine-aspartic acid (RGD) peptides preferentially bind to alphavbeta3
      integrin, an integrin expressed on newly formed endothelial cells and on various
      tumor cells. When labeled with beta-emitting radionuclides, these peptides can be
      used for peptide-receptor radionuclide therapy of malignant tumors. These studies
      aimed to investigate whether tumor targeting and tumor therapy could be optimized
      by dose fractionation. The RGD-peptide DOTA-E-[c(RGDfK)]2 was labeled with 111In
      for biodistribution experiments and with 90Y for therapy experiments. In mice
      with NIH:OVCAR-3 ovarian carcinoma xenografts, optimal tumor uptake was obtained
      at peptide doses up to 1.0 microg (4.8 %ID/g). A peptide dose of 5 microg,
      required to administer the maximum tolerable dose (MTD) 90Y-DOTA-E-[c(RGDfK)]2,
      was administered as 5 portions of 1.0 microg. Tumor uptake of the fifth portion
      was significantly higher than that of the single 5.0 microg portion (3.3 %ID/g
      versus 2.1 %ID/g). The therapeutic efficacy of 37 MBq 90Y-DOTA-E-[c(RGDfK)]2 (1 x
      5.0 microg) was compared with that of 37 MBq administered in five equal portions
      (5 x 1.0 microg). No difference in tumor growth between the fractionated and the
      nonfractionated therapy was observed. In conclusion, dose fractionation resulted
      in higher radiation doses. However, therapeutic efficacy of the radiolabeled
      peptide was not significantly improved by dose fractionation.

PMID- 15453955
TI  - A theoretical approach for T-lymphocyte monitoring of autologous cancer vaccine
      therapy using autologous HLA-class I and HLA-class II constructs.
AB  - It is desirable to have in vitro surrogate endpoints that reflect changes in
      cellular immunity in patients who are undergoing treatment with anticancer,
      autologous, tumor-cell vaccines. The tetramer assay appears to be useful for
      monitoring T-lymphocyte responses to a single, specific, known tumor peptide
      antigen, but cell-based vaccines may express multiple tumor-associated antigens
      that are important in a host immune response to their own cancer. We describe a
      hypothetical alternative to the standard artificial tetramer assay, that has the
      potential to detect CD4+ and CD8+ T-lymphocytes that react with any peptides
      expressed in the context of HLA-class I or HLA-class II. Such an assay should
      enable monitoring for specific T-lymphocyte antitumor activity in patients being
      treated with patient specific, autologous, tumor-cell vaccines.

PMID- 15453956
TI  - Influence of glutathione depletion on plasma membrane cholesterol esterification
      and on Tc-99m-sestamibi and Tc-99m-tetrofosmin uptakes: a comparative study in
      sensitive U-87-MG and multidrug-resistant MRP1 human glioma cells.
AB  - In our previous studies, we demonstrated a possible effect of cellular
      glutathione (GSH) depletion on plasma-membrane permeability and fluidity in
      glioma-cell lines. We therefore investigated the effect of GSH modulation on
      accumulation of two radiotracers, Tc-99m-sestamibi (MIBI) and Tc-99m-tetrofosmin
      (TFOS), and on plasma-membrane cholesterol content in sensitive U-87-MG and
      resistant U-87-MG-CIS and U-87-MG-MEL (MRP1 positive) human glioma-cell lines.
      GSH depletion was mediated by BSO pretreatment and addition of N-acetylcysteine
      reversed the effect. MIBI and TFOS uptakes, total cholesterol, and cholesteryl
      ester contents were evaluated under each condition. In contrast with TFOS, MIBI
      accumulation was inversely proportional to the cell multidrug resistance
      phenotype. Similar cholesterol contents were observed in all cell lines,
      demonstrating that MRP1 did not modify lipid membrane composition. A decrease of
      intracellular GSH allows an increase of plasma-membrane cholesterol and a
      decrease of cholesteryl-ester content, which in turn results in spectacular TFOS
      uptake. The GSH status of the cells plays an important role in the plasma
      membrane cholesterol composition and TFOS uptake, which appears to be
      particularly sensitive to this modification. In contrast with MIBI, TFOS is not
      an MRP1 probe in glioma cells, and therefore appears to be a suitable tracer in
      this indication.

PMID- 15453957
TI  - Ginger (Zingiber officinale Rosc.), a dietary supplement, protects mice against
      radiation-induced lethality: mechanism of action.
AB  - The radioprotective effect of hydroalcoholic extract of ginger rhizome (Zingiber
      officinale; ZOE) was studied in mice administered 250 mg/kg ZOE orally using oral
      gavage once daily for 5 consecutive days before exposure to 6, 7, 8, 9, 10, or 11
      Gy of gamma-radiation. The animals were monitored daily up to 30 days
      postirradiation for the development of symptoms of radiation sickness and
      mortality. Pretreatment of mice with ZOE reduced the severity of symptoms of
      radiation sickness and mortality at all the exposure doses and also increased the
      number of survivors in a ZOE + irradiation group compared to the concurrent
      double-distilled water + irradiation group. The ZOE treatment protected mice
      against gastrointestinal-related deaths as well as bone-marrow-related deaths.
      The dose-reduction factor was found to be 1.2. The administration of ZOE after
      exposure to irradiation was not effective, as no survivors lasted up to 30 days
      postirradiation. Reducing the administration schedule to 3 days or increasing the
      schedule to 7 days was not as effective compared to a 5 consecutive days'
      schedule. The irradiation of animals resulted in a dose-dependent elevation in
      the lipid peroxidation, while depletion in the glutathione (GSH) contents
      occurred on day 31 postirradiation. Treatment of mice with ZOE before irradiation
      caused a significant depletion in lipid peroxidation followed by a significant
      elevation in GSH concentration in the livers of mice at 31 days postirradiation.
      The mechanism of action of ZOE was determined by evaluating its free-radical
      scavenging capability. Ginger was found to scavenge *OH, O2*- and ABTS*+ radicals
      in a dose-dependent manner in vitro. The drug was nontoxic up to a dose of 1500
      mg/kg body weight, the highest drug dose that could be tested for acute toxicity.

PMID- 15453958
TI  - [18F]3'-deoxy-3'-fluorothymidine-PET in NHL patients: whole-body biodistribution
      and imaging of lymphoma manifestations--a pilot study.
AB  - OBJECTIVE: The nucleoside 3'-deoxy-3'-fluorothymidine (alovudine) is an antiviral
      agent accumulating in proliferating cells. We prospectively evaluated the
      biodistribution of the PET tracer [18F]3'-deoxy-3'-fluorothymidine (FLT) and its
      value in detecting manifestations of non-Hodgkin's lymphoma (NHL). METHODS: In
      this pilot study, 7 patients (6 male, 1 female) with indolent NHL (2), NHL in
      transformation (2) or aggressive NHL (3) were examined. Patients received initial
      staging or restaging with an interval of at least 10 weeks between therapy and
      positron emission tomography (PET). Mean doses of 324 +/- 165 MBq FLT were
      injected intravenously. Static PET scans were performed 50-70 minutes after
      application. Maximum standardized uptake values (SUV) of organs and NHL
      manifestations were calculated. FLT-positive lesions were verified by biopsies (3
      lesions) or aspiration smears (5 lesions in 4 patients). RESULTS:
      Biodistribution: The tracer accumulated physiologically in hematopoietic marrow
      and in the liver. It was renally excreted. SUV of organs 1 hour after injection
      were: bones with hematopoietic marrow, 9.9 +/- 4.7; liver, 5.2 +/- 1.0; kidneys,
      4.0 +/- 1.7; spleen, 3.0 +/- 1.2; bones without hematopoietic marrow, 1.9 +/-
      1.1; lungs, 0.8 +/- 0.3. NHL manifestations: In 7 patients, diagnosis was
      verified as true positive by histology/cytology. Maximum lymphoma SUV of FLT
      positive lesions were 6 for the indolent group and 8-11 for lymphoma in
      transformation. In the aggressive group, SUV were 6, 14, and 17. The low SUV in
      this group was found in a highly proliferate large-cell anaplastic lymphoma
      combined with marked sclerosis of 30%. CONCLUSIONS: In this pilot study, FLT-PET
      was suitable in the imaging of NHL manifestations. In NHL with normal
      cellularity, FLT accumulated more intensely in aggressive NHL and NHL in
      transformation than in indolent NHL. Bones with hematopoietic marrow and the
      liver were the organs with the highest physiological uptake.

PMID- 15453959
TI  - Assessment of therapeutic tumor response using 99mtc-ethylenedicysteine
      glucosamine.
AB  - PURPOSE: The aim of this study was to evaluate 99mTc-ethylenedicysteine
      glucosamine (EC-DG) for the assessment of tumor growth. METHOD: To evaluate
      whether 99mTc-EC-DG is involved in cell nuclei activity, in vitro thymidine
      incorporation, and cell-cycle assays of EC-DG were conducted using lung and
      breast cancer cells. Biodistribution of 99mTc-EC-DG in lung tumor-bearing mice
      (0.5-4 hours, 1 Ci/mouse, i. v.) was used to estimate the radiation-absorbed
      dose. Autoradiograms of 99mTc-EC-DG and 18F-FDG were compared in nude mice
      bearing uterine sarcoma. Rabbits inoculated with VX-2 cells were imaged with
      99mTc-EC-DG and 99mTc-EC. For therapeutic assessment studies, scintigraphic
      imaging studies with 99mTc-EC-DG in mammary tumor-bearing rats were conducted at
      various days after treatment with paclitaxel and cisplatin. The imaging findings
      were correlated immunohistochemical assays (mRNA expression, apoptosis, and cell
      cycle changes in tumor), and flow cytometry analysis was performed. RESULTS: In
      vitro cellular uptake assays indicated that cell nuclei activity could be
      assessed by 99mTc-EC-DG. Scintigraphy and autoradiograms in animal models
      demonstrated that the tumor could be clearly visualized by 99mTc-EC-DG. The
      efficacy of paclitaxel and cisplatin treatment in rodent models could be assessed
      using tumor/muscle ratios. Immunohistochemical staining indicated a reduced
      expression of bFGF and an increased apoptosis and cell-cycle changes after
      paclitaxel and cisplatin treatment. CONCLUSION: 99mTc-EC-DG is involved in cell
      nuclei activity and could assess the therapeutic tumor response.

PMID- 15453960
TI  - Tracers to monitor the response to chemotherapy: in vitro screening of four
      radiopharmaceuticals.
AB  - OBJECTIVES: It has been postulated that radiopharmaceuticals can be used to
      predict the therapeutic response to (chemo)therapy, which could lead to
      individualized treatment regimens. In this study, 18F-deoxyglucose, 99mTc
      tetrofosmin, 125I-deoxyuridineribose, and 125I-methyltyrosine were tested for
      this purpose. METHODS: The uterine sarcoma cell line MES-SA (MDR-) and its
      multidrug resistant variant, MES-SA/Dx5 (MDR+), were used. The MDR+ cells express
      high levels of P-glycoprotein, which makes them relatively resistant to various
      chemotherapeutic agents. Cells were cultured in the presence of escalating
      concentrations of doxorubicin, and the cellular uptake of the
      radiopharmaceuticals was determined. RESULTS: Decreasing 18F-deoxyglucose uptake
      at escalating doxorubicin concentrations reflected the chemosensitivity of the
      cells: 18F-deoxyglucose uptake in the MDR- cells was reduced to 40% of the
      baseline level in the presence of 1 microM of doxorubicin, compared to 74% in the
      MDR+ cells. The 125I-deoxyuridineribose uptake in MDR- cells was reduced to 2% of
      the baseline level when cultured at a concentration of 1 microM of doxorubicin,
      while this was 79% in the MDR+ cells. The same trend was observed with 125I
      methyltyrosine. The enhanced doxorubicin chemosensitivity of MDR+ cells in the
      presence of verapamil, a modulator of P-glycoprotein, was reflected by the
      reduced uptake of 18F-deoxyglucose, 125I-deoxyuridineribose, and 125I
      methyltyrosine. Furthermore, baseline 99mTc-tetrofosmin uptake in MDR+ cells was
      more than six-fold lower than in MDR- cells. CONCLUSION: In the presence of
      doxorubicin, the uptake of 18F-deoxyglucose, 125I-deoxyuridineribose and, to a
      lesser extent, 125I-methyltyrosine is more pronouncedly reduced in MDR- cells
      than in MDR+ cells. The reversal of doxorubicin-resistance of MDR+ cells by
      verapamil was also reflected by the uptake of 18F-deoxyglucose, 125I
      deoxyuridineribose, and 125I-methyltyrosine. 99mTc-tetrofosmin uptake reflected P
      glycoprotein expression without exposure to doxorubicin.

PMID- 15453961
TI  - Pharmacokinetics and tumor targeting of 131I-labeled F(ab')2 fragments of the
      chimeric monoclonal antibody G250: preclinical and clinical pilot studies.
AB  - INTRODUCTION: Clinical and animal studies of chimeric monoclonal antibody G250
      (moAb cG250) for the targeting of clear-cell renal cell carcinoma (RCC), to date,
      have been with the intact IgG form. To determine whether F(ab')2 fragments are
      more suited for radioimmunotherapy (RIT) than intact IgG, biodistribution
      experiments in nude mice were performed, and a pilot study in RCC patients was
      carried out. In these studies, the biodistribution, pharmacokinetics, and tumor
      targeting characteristics of 131I-cG250-F(ab')2 fragments were determined.
      METHODS: The biodistribution of intact IgG and F(ab')2 fragments (moAb cG250) was
      directly compared in mice with subcutaneous (s.c.) RCC xenografts that were
      coinjected with 125I-cG250-IgG and 131I-cG250-F(ab')2 fragments. Groups of 5 mice
      were dissected at 1, 2, 3, 5, and 7 days postinjection (p.i.). The activity in
      tumor and normal tissues was expressed as the percentage of the injected dose per
      gram (%ID/g). Five (5) patients with evidence of primary RCC on computed
      tomography (CT) and scheduled for nephrectomy received a diagnostic infusion of
      150 MBq 131I-cG250-F(ab')2. At various time points after injection of the
      antibody preparation (5 minutes, 3 hours, and 1, 2, 3, and 4 days), whole-body
      gamma camera images were acquired. After surgery, histology was determined and
      immunohistochemistry was performed. The scintigraphic images were analyzed
      visually and quantitatively. Radioactivity in whole-body, normal tissues and
      primary RCC was calculated and expressed as %ID. RESULTS: In mice, 131I-cG250
      F(ab')2 fragments cleared faster from the blood and other tissues, and absolute
      uptake in tumor (3.4 +/- 0.9 %ID/g at 24 hours p.i.) and normal tissues was
      considerably lower compared to intact 125I-cG250. However, the tissue-to-blood
      ratios for both antibody preparations were similar for most tissues and at most
      time points. The results in patients corresponded with the results of the studies
      in mice. The 131I-cG250-F(ab')2 fragments cleared rapidly from the blood and
      body. The half-life of the distribution and elimination phase (t(1/2)alpha and
      t(1/2)beta) in blood of RCC patients were 4.8 +/- 0.9 hours and 29.0 +/- 3.3
      hours, respectively. At 4 days p.i., whole-body activity was 20%ID. Faint
      visualization of tumor was observed in only 2 of 5 patients. CONCLUSIONS: In
      mice, the tissue-to-blood ratios were similar for intact IgG and the 131I-cG250
      F(ab')2 fragments for most tissues and at most time points, although absolute
      uptake in all tissues was considerably lower for the F(ab')2 fragments. In
      patients with primary RCC, tumorous kidney tissue was faintly visualized with
      131I-cG250-F(ab')2 fragments. The intact IgG form of cG250 appears to be more
      suitable than cG250-F(ab')2 fragments for targeting clear-cell RCC.

PMID- 15453962
TI  - Follow-up results of a phase II study of ibritumomab tiuxetan radioimmunotherapy
      in patients with relapsed or refractory low-grade, follicular, or transformed B
      cell non-Hodgkin's lymphoma and mild thrombocytopenia.
AB  - This report presents updated time-to-event variables from a multicenter phase II
      trial of reduced-dose 90Y ibritumomab tiuxetan in patients with relapsed or
      refractory low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma
      (NHL) and mild thrombocytopenia (platelet counts of 100 to 149 x 10(9)
      platelets/L). Patients received a single course of ibritumomab tiuxetan
      radioimmunotherapy, with 90Y ibritumomab tiuxetan administered at 0.3 mCi/kg
      (compared to a standard dose of 0.4 mCi/kg). In 30 patients, the overall response
      rate was 83%, with complete responses (confirmed [CR] and unconfirmed [CRu]) of
      47%. Median follow-up time is currently 36.5 months (range: 7.5-54.9+ months).
      Median duration of response was 11.5 months (range: 1.0-53.9 months), median time
      to progression was 9.4 months (range: 1.7-54.8+ months), and median time to next
      lymphoma therapy was 14.6 months (range: 2.3-54.9 months). Median overall
      survival time has not yet been reached. Long-term responses, defined as time to
      progression of 12 months or greater, have been seen in 14 of 30 patients (47%)
      overall, and 12 of 14 CR/CRu patients (86%). Toxicities were primarily
      hematologic and reversible. No additional long-term adverse events have been
      observed in the follow-up period, and treatment did not preclude subsequent
      lymphoma therapies.

PMID- 15453963
TI  - Quantitative imaging of yttrium-86 PET with the ECAT EXACT HR+ in 2D mode.
AB  - The radionuclide 86Y potentially allows for the precise assessment of tissue
      radioactivity biodistribution and, thus, extrapolation of a therapeutic dose of
      90Y-labeled compounds. A method to obtain quantitative images from 86Y-PET
      measurements after a background correction and a recalibration is presented.
      Cylinder and body phantom measurements with 18 F and 86Y using an ECAT EXACT HR+
      tomograph were performed in 2D mode. A second-order series expansion is used to
      correct for the background of spurious coincidences in the sinogram. A
      recalibration of the positron emission tomography (PET) system, depending on the
      ratio of true coincidences and singles, is implemented. The correction for the
      nonannihilation coincidences with a second-order series expansion significantly
      improves the accuracy of quantitation: The lesion-to-background ratio is
      reproduced, and the variation of the activity concentration in the homogeneous
      background regions of the phantoms is smaller than 5%. The apparent activities in
      cold inserts of various densities is reduced to less than 15% of the
      concentration in the active region. The recalibration of the system works with a
      relative error of 0.2% +/- 2.4%. In conclusion, the used approximations lead to
      improved uniformity and quantitative accuracy in 86Y-PET measurements with the
      ECAT EXACT HR+.

PMID- 15453964
TI  - Comparative biodistribution of potential anti-glioblastoma conjugates [111In]DTPA
      hEGF and [111In]Bz-DTPA-hEGF in normal mice.
AB  - EGF-receptors (EGFR) are overexpressed in gliomas, as well as in tumors of
      breast, lung, and urinary bladder. For this reason, EGFR may be an attractive
      target for both visualization and therapy of malignant tumors using radioactive
      nuclides. Natural ligand of EGFR, epidermal growth factor (EGF) is a small 53
      amino-acid protein. Low molecular weight of EGF may enable better intratumoral
      penetration in comparison to antibodies. [111In]DTPA-EGF was proposed for the
      targeting of glioblastoma and breast cancer, and its tumor-seeking properties
      were confirmed in animal studies. The aim of this study was to evaluate how the
      substitution of heptadentate DTPA for octadentate benzyl-DTPA (Bz-DTPA) effects
      the biodistribution of indium-labeled human EGF (hEGF) in normal NMRI mice.
      [111In]DTPA-hEGF and [111In]Bz-DTPA-hEGF, obtained by the coupling of ITC-benzyl
      DTPA to hEGF, were injected into the tail vein. At 0.5, 1, 4, and 24 hours
      postinjection, the animals were sacrificed, and radioactivity in different organs
      was measured. The blood clearance of both conjugates was fast. The uptake of both
      conjugates in the liver, spleen, stomach, pancreas, intestines, and submaxillary
      gland was most likely receptor-mediated. The uptake in a majority of organs was
      similar. However, indium uptake in the case of [111In]DTPA-hEGF was significantly
      higher in the kidneys and bones. In conclusion, [111In]Bz-DTPA-hEGF seems to have
      more favourable in vivo distribution in comparison to [111In]DTPA-hEGF.

PMID- 15453968
TI  - The cerebellum and English grammatical morphology: evidence from production,
      comprehension, and grammaticality judgments.
AB  - Three neuropsychological experiments on a group of 16 cerebellar patients and 16
      age- and education-matched controls investigated the effects of damage to the
      cerebellum on English grammatical morphology across production, comprehension,
      and grammaticality judgment tasks. In Experiment 1, participants described a
      series of pictures previously used in studies of cortical aphasic patients. The
      cerebellar patients did not differ significantly from the controls in the total
      number of words produced or in the proportion of closed-class words. They did
      differ to a marginally significant extent in the production of required articles.
      In Experiment 2, participants identified the agent in a series of aurally
      presented sentences in which three agency cues (subject-verb agreement, word
      order, and noun animacy) were manipulated. The cerebellar patients were less
      affected than the controls were by the manipulation of subject-verb agreement to
      a marginally significant extent. In Experiment 3, participants performed a
      grammaticality judgment task on a series of aurally presented sentences. The
      cerebellar patients were significantly less able to discriminate grammatical and
      ungrammatical sentences than the controls were, particularly when the error was
      of subject-verb agreement as opposed to word order. The results suggest that
      damage to the cerebellum can result in subtle impairments in the use of
      grammatical morphology, and are discussed in light of hypothesized roles for the
      cerebellum in language.

PMID- 15453969
TI  - Dissociating confidence and accuracy: functional magnetic resonance imaging shows
      origins of the subjective memory experience.
AB  - Successful memory typically implies both objective accuracy and subjective
      confidence, but there are instances when confidence and accuracy diverge. This
      dissociation suggests that there may be distinct neural patterns of activation
      related to confidence and accuracy. We used event-related functional magnetic
      resonance imaging to study the encoding of novel face--name associations,
      assessed with a postscan memory test that included objective measures of accuracy
      and subjective measures of confidence. We showed specific neural activity in the
      left inferior prefrontal cortex associated with trials when subjects expressed
      high confidence that they had chosen the correct name for the face and made a
      correct identification. Moreover, we found that this region was also associated
      with imparting high confidence when subjects chose the incorrect name. However,
      medial temporal lobe regions showed activity only for high-confidence correct
      trials. Many functional magnetic resonance imaging studies have shown that the
      medial temporal lobe and left prefrontal regions are particularly important for
      the successful formation of memories by using a combination of subjective and
      objective measures. Our findings suggest that these regions may be differentially
      involved in the objective and subjective components of memory and that the
      origins of confidence-accuracy dissociations may be related to incomplete
      activation of the neural pattern seen in successful encoding. These findings may
      also aid understanding of eyewitness misidentifications and memory distortions.

PMID- 15453970
TI  - Cortical regions for judgments of emotions and personality traits from point
      light walkers.
AB  - Humans are able to use nonverbal behavior to make fast, reliable judgments of
      both emotional states and personality traits. Whereas a sizeable body of research
      has identified neural structures critical for emotion recognition, the neural
      substrates of personality trait attribution have not been explored in detail. In
      the present study, we investigated the neural systems involved in emotion and
      personality trait judgments. We used a type of visual stimulus that is known to
      convey both emotion and personality information, namely, point-light walkers. We
      compared the emotion and personality trait judgments made by subjects with brain
      damage to those made by neurologically normal subjects and then conducted a
      lesion overlap analysis to identify neural regions critical for these two tasks.
      Impairments on the two tasks dissociated: Some subjects were impaired at emotion
      recognition, but judged personality normally; other subjects were impaired on the
      personality task, but normal at emotion recognition. Moreover, these
      dissociations in performance were associated with damage to specific neural
      regions: Right somatosensory cortices were a primary focus of lesion overlap in
      subjects impaired on the emotion task, whereas left frontal opercular cortices
      were a primary focus of lesion overlap in subjects impaired on the personality
      task. These findings suggest that attributions of emotional states and
      personality traits are accomplished by partially dissociable neural systems.

PMID- 15453971
TI  - Deficits for semantics and the irregular past tense: a causal relationship?
AB  - The regular and irregular past tense has become a focus for recent debates about
      the structure of the language processing system, asking whether language
      functions are subserved by different neural and functional mechanisms or whether
      all processes can be accommodated within a single unified system. A critical
      claim of leading single mechanism accounts is that the relationship between an
      irregular stem and its past tense form is primarily semantic and not
      morphological in nature. This predicts an obligatory relationship between
      semantic performance and access to the irregular past tense, such that a semantic
      deficit necessarily leads to impairments on the irregulars. We tested this claim
      in a series of studies probing the comprehension and production of regular and
      irregular past tense forms in four semantic dementia patients, all of whom had
      profound semantic deficits. In two elicitation tasks and one auditory priming
      study, we found that three out of the four patients did not have a deficit for
      the irregular past tense, in spite of their semantic deficits. This argues
      against the view that the relationship between irregular past tense forms and
      their stems is primarily semantic, and more generally against the single system
      claim that morphological structure can be captured solely based on phonological
      and semantic relationships.

PMID- 15453972
TI  - Neural bases of talker normalization.
AB  - To recognize phonemes across variation in talkers, listeners can use information
      about vocal characteristics, a process referred to as "talker normalization." The
      present study investigates the cortical mechanisms underlying talker
      normalization using fMRI. Listeners recognized target words presented in either a
      spoken list produced by a single talker or a mix of different talkers. It was
      found that both conditions activate an extensive cortical network. However,
      recognizing words in the mixed-talker condition, relative to the blocked-talker
      condition, activated middle/superior temporal and superior parietal regions to a
      greater degree. This temporal-parietal network is possibly associated with
      selectively attending and processing spectral and spatial acoustic cues required
      in recognizing speech in a mixed-talker condition.

PMID- 15453973
TI  - Judging time intervals using a model of perceptuo-motor control.
AB  - Estimating a time interval and temporally coordinating movements in space are
      fundamental skills, but the relationships between these different forms of
      timing, and the neural processes that they incur, are not well understood. While
      different theories have been proposed to account for time perception, time
      estimation, and the temporal patterns of coordination, there are no general
      mechanisms which unify these various timing skills. This study considers whether
      a model of perceptuo-motor timing, the tau(GUIDE), can also describe how certain
      judgements of elapsed time are made. To evaluate this, an equation for
      determining interval estimates was derived from the tau(GUIDE) model and tested
      in a task where participants had to throw a ball and estimate when it would hit
      the floor. The results showed that in accordance with the model, very accurate
      judgements could be made without vision (mean timing error -19.24 msec), and the
      model was a good predictor of skilled participants' estimate timing. It was
      concluded that since the tau(GUIDE) principle provides temporal information in a
      generic form, it could be a unitary process that links different forms of timing.

PMID- 15453974
TI  - Neural correlates of retrieval orientation: effects of study-test similarity.
AB  - ERPs elicited by correctly classified unstudied items in tests of yes/no
      recognition memory were used to investigate the neural correlates of retrieval
      cue processing. Items in Experiment 1 consisted of pictures and their
      corresponding names, allowing study and test material to be factorially crossed
      in four separate study-test cycles. The ERPs elicited by unstudied pictures and
      words were, in each case, more negative-going when the study material belonged to
      the alternative rather than the same class of items. These findings demonstrate
      that previously reported ERP "retrieval orientation effects" depend on
      differences in similarity between study and test items, and not on the form of
      the sought for material. In Experiments 2a and 2b, study materials were auditory
      words and pictures, and the test items were visual words. In both experiments,
      ERPs elicited by unstudied test words were more negative-going when pictures
      rather than auditory words were the study material. Thus, ERP retrieval
      orientation effects do not depend on the employment of a copy cue condition. It
      is proposed that the effects reflect differences in the processing necessary to
      maximize overlap between cue and memory representations.

PMID- 15453975
TI  - Maturation of white matter is associated with the development of cognitive
      functions during childhood.
AB  - In the human brain, myelination of axons continues until early adulthood and is
      thought to be important for the development of cognitive functions during
      childhood. We used diffusion tensor MR imaging and calculated fractional
      anisotropy, an indicator of myelination and axonal thickness, in children aged
      between 8 and 18 years. Development of working memory capacity was positively
      correlated with fractional anisotropy in two regions in the left frontal lobe,
      including a region between the superior frontal and parietal cortices. Reading
      ability, on the other hand, was only correlated with fractional anisotropy in the
      left temporal lobe, in the same white matter region where adults with reading
      disability are known to have lower fractional anisotropy. Both the temporal and
      the frontal regions were also correlated with age. These results show that
      maturation of white matter is an important part of brain maturation during
      childhood, and that maturation of relatively restricted regions of white matter
      is correlated with development of specific cognitive functions.

PMID- 15453976
TI  - Development of brain mechanisms for processing orthographic and phonologic
      representations.
AB  - Developmental differences in the neurocognitive networks for lexical processing
      were examined in 15 adults and 15 children (9- to 12-year-olds) using functional
      magnetic resonance imaging (fMRI). The lexical tasks involved spelling and
      rhyming judgments in either the visual or auditory modality. These lexical tasks
      were compared with nonlinguistic control tasks involving judgments of line
      patterns or tone sequences. The first main finding was that adults showed greater
      activation than children during the cross-modal lexical tasks in a region
      proposed to be involved in mapping between orthographic and phonologic
      representations. The visual rhyming task, which required conversion from
      orthography to phonology, produced greater activation for adults in the angular
      gyrus. The auditory spelling task, which required the conversion from phonology
      to orthography, also produced greater activation for adults in the angular gyrus.
      The greater activation for adults suggests they may have a more elaborated
      posterior heteromodal system for mapping between representational systems. The
      second main finding was that adults showed greater activation than children
      during the intra-modal lexical tasks in the angular gyrus. The visual spelling
      and auditory rhyming did not require conversion between orthography and phonology
      for correct performance but the adults showed greater activation in a system
      implicated for this mapping. The greater activation for adults suggests that they
      have more interactive convergence between representational systems during lexical
      processing.

PMID- 15453977
TI  - The effect of phonological repetition on cortical magnetic responses evoked by
      visually presented words.
AB  - Neuroimaging studies have reported that the left superior temporal cortical area
      is activated by visually presented words. In the present study, we recorded
      cortical magnetic responses evoked by visual words and examined the effect of
      phonological repetition (e.g., hair-hare) on left superior temporal cortical
      activity, using pairs of homophonic Japanese words as stimuli. Unlike English,
      Japanese has a large number of homophone pairs with a totally different
      orthography. By taking advantage of this feature of the Japanese writing system,
      the effect of phonological repetition can be solely examined without being
      confounded by the effect of orthographic similarity. Magnetic responses were
      recorded over the bilateral temporal sites of the brain while subjects silently
      read words. The words were presented one by one; a quarter of them was
      immediately followed by a homophonic word. Clear magnetic responses in the
      latency range of 300-600 msec were observed in the left hemisphere, and the
      responses to the homophones were smaller than those to the first presented words.
      In the right hemisphere, clear responses were not consistently recorded in the
      same latency range, and no effect of phonological repetition was observed. The
      sources of the responses recorded over the left hemisphere were estimated to be
      in the left superior temporal cortical area adjacent to the auditory cortex and
      the source strength as well as the magnetic responses showed a reduction by
      phonological repetition. This result suggests that the activity in the left
      superior temporal cortical area is associated with access to the phonological
      representation of words.

PMID- 15453978
TI  - An event-related fMRI study of exogenous orienting: supporting evidence for the
      cortical basis of inhibition of return?
AB  - This event-related fMRI experiment examined the neural substrates of exogenous
      visuospatial attention. Exogenous attention produces a biphasic response pattern
      denoted by facilitation at short cue-target intervals and inhibition of return
      (IOR) at longer intervals. Whereas the volitional orienting of attention has been
      well described in the literature, the neural systems that support exogenous
      facilitation and IOR in humans are relatively unknown. In direct comparisons to
      valid facilitation trials, valid IOR trials produced unique foci of activation in
      the right posterior parietal, superior temporal, middle temporal, middle
      occipital, anterior cingulate, and dorsal medial thalamic areas. Valid IOR trials
      also resulted in activation of motor exploratory and frontal areas previously
      associated with inhibition and oculomotor control. In contrast, invalid IOR
      compared to facilitation trials only activated anterior cortical structures.
      These results provide support for both attentional and oculomotor theories of IOR
      and suggest that IOR may be mediated by two networks. One network may mediate the
      inhibitory bias following an exogenous cue, whereas a separate network may be
      activated when a response must be made to stimuli that appear in inhibited
      locations of space.

PMID- 15453979
TI  - Anticipating words and their gender: an event-related brain potential study of
      semantic integration, gender expectancy, and gender agreement in Spanish sentence
      reading.
AB  - Recent studies indicate that the human brain attends to and uses grammatical
      gender cues during sentence comprehension. Here, we examine the nature and time
      course of the effect of gender on word-by-word sentence reading. Event-related
      brain potentials were recorded to an article and noun, while native Spanish
      speakers read medium- to high-constraint Spanish sentences for comprehension. The
      noun either fit the sentence meaning or not, and matched the preceding article in
      gender or not; in addition, the preceding article was either expected or
      unexpected based on prior sentence context. Semantically anomalous nouns elicited
      an N400. Gender-disagreeing nouns elicited a posterior late positivity (P600),
      replicating previous findings for words. Gender agreement and semantic congruity
      interacted in both the N400 window--with a larger negativity frontally for double
      violations--and the P600 window--with a larger positivity for semantic anomalies,
      relative to the prestimulus baseline. Finally, unexpected articles elicited an
      enhanced positivity (500-700 msec post onset) relative to expected articles.
      Overall, our data indicate that readers anticipate and attend to the gender of
      both articles and nouns, and use gender in real time to maintain agreement and to
      build sentence meaning.

PMID- 15453980
TI  - Context-dependent deactivation of the amygdala during pain.
AB  - The amygdala has been implicated in fundamental functions for the survival of the
      organism, such as fear and pain. In accord with this, several studies have shown
      increased amygdala activity during fear conditioning and the processing of fear
      relevant material in human subjects. In contrast, functional neuroimaging studies
      of pain have shown a decreased amygdala activity. It has previously been proposed
      that the observed deactivations of the amygdala in these studies indicate a
      cognitive strategy to adapt to a distressful but in the experimental setting
      unavoidable painful event. In this positron emission tomography study, we show
      that a simple contextual manipulation, immediately preceding a painful
      stimulation, that increases the anticipated duration of the painful event leads
      to a decrease in amygdala activity and modulates the autonomic response during
      the noxious stimulation. On a behavioral level, 7 of the 10 subjects reported
      that they used coping strategies more intensely in this context. We suggest that
      the altered activity in the amygdala may be part of a mechanism to attenuate pain
      related stress responses in a context that is perceived as being more aversive.
      The study also showed an increased activity in the rostral part of anterior
      cingulate cortex in the same context in which the amygdala activity decreased,
      further supporting the idea that this part of the cingulate cortex is involved in
      the modulation of emotional and pain networks.

PMID- 15453981
TI  - Brain signatures of syntactic and semantic processes during children's language
      development.
AB  - Developmental aspects of language comprehension were investigated using event
      related brain potentials. Children between the ages of 6 and 13 listened to
      passive sentences that were correct, semantically incorrect, or syntactically
      incorrect, and data in each condition were compared with those of adults. For
      semantic violations, adults demonstrated a negativity (N400), as did children,
      but the latency decreased with age. For syntactic violations, adults displayed an
      early left anterior negativity (ELAN) and a late centro-parietal positivity
      (P600). A syntactic negativity and a late positivity were also present for
      children between 7 and 13 years, again with latency decreasing with age. Six-year
      olds, in contrast, did not demonstrate an ELAN effect, but a late, reduced P600
      pattern for the syntactic violation condition. In the early time window, the 6
      year-olds displayed a widely distributed negativity that was larger for the
      correct than for the syntactically incorrect condition. These data indicate that
      the neurophysiological basis for semantic processes during auditory sentence
      comprehension does not change dramatically between early childhood and adulthood.
      Syntactic processes for passive sentences appear to differ between early and late
      childhood, at least with respect to those processes reflected in the ELAN
      component. As there is evidence that the ELAN reflects highly automatic structure
      building processes, we conclude that these processes are not yet established at
      age 7, but gradually develop toward adult-like processing during late childhood.

PMID- 15453982
TI  - Continuous versus intermittent cerebrospinal fluid drainage after severe
      traumatic brain injury in children: effect on biochemical markers.
AB  - Drainage of cerebrospinal fluid (CSF) is routinely used in the treatment of
      severe traumatic brain injury (TBI), either continuously or intermittently in
      response to increases in intracranial pressure (ICP). There has been little study
      of the effect of CSF drainage method on the biochemistry, pathophysiology or
      outcome of TBI in adults or children. Having previously reported that a variety
      of markers of injury or repair increase in CSF after severe TBI, we chose to
      evaluate directly the effect of CSF drainage method on the biochemistry and
      volume of CSF drained as well as ICP. We hypothesized that concentrations of
      these markers would be similar in CSF drained continuously vs intermittently. We
      compared CSF levels of markers of neuronal injury (neuron specific enolase,
      [NSE]), glial injury (s100B), inflammation (interleukin-6 [IL-6]), and
      regeneration (vascular endothelial growth factor [VEGF]) (measured by ELISA) in
      80 CSF samples from 19 severely injured children whose CSF was drained
      continuously (n = 13) versus intermittently (n = 6) as part of standard care in
      two institutions. Compared to continuous CSF drainage, intermittent drainage of
      CSF was associated with twofold greater CSF concentrations of NSE, s100B, IL-6
      and VEGF (p < 0.05) and with about half the volume of CSF removal than continuous
      drainage (p = 0.002). The resulting elimination (concentration x volume) of these
      biochemicals, however, was not influenced by drainage method. Patients treated
      with continuous drainage had lower mean ICPs than those with intermittent
      drainage (13.6 +/- 0.69 vs. 21.8 +/- 0.95 mm Hg, p < 0.0001). We conclude that
      the method of CSF drainage greatly affects concentrations of CSF markers after
      TBI and may influence ICP. The influence of method on CSF marker concentration
      must be kept in mind when interpreting studies of CSF biomarkers. The striking
      difference in biomarker concentration, CSF volume drained, and ICP suggests the
      need for a randomized trial directly comparing these two approaches in infants
      and children with severe TBI.

PMID- 15453983
TI  - Assessment of the macrophage marker quinolinic acid in cerebrospinal fluid after
      pediatric traumatic brain injury: insight into the timing and severity of injury
      in child abuse.
AB  - This study measured quinolinic acid (QUIN), a macrophage-microglia derived
      neurotoxin, in the cerebrospinal fluid (CSF) of children after non-inflicted and
      inflicted traumatic brain injury (nTBI, iTBI), and correlated QUIN concentrations
      with age, mechanism of injury (nTBi vs. iTBI), Glasgow Coma Scale (GCS) score and
      6-month Glasgow Outcome Score. One hundred fifty-two CSF samples were collected
      from 51 children with severe TBI (GCS < or = 8). CSF was collected at the time an
      intraventricular catheter was placed and daily thereafter. QUIN concentration was
      measured by gas chromatography-mass spectroscopy. Patients ranged in age from 2
      months to 16 years. Eleven children (22%) had iTBI. Initial and peak CSF QUIN
      concentrations were higher in patients with iTBI versus nTBI after adjusting for
      time after injury and GCS. Despite the lack of a history of trauma in 82% of
      children with iTBI, 100% had a peak QUIN concentration of >100 nM. There was a
      significant increase in the CSF concentrations of QUIN following severe nTBI and
      iTBI in children. Higher initial and peak QUIN concentrations after iTBI may be
      due to severity of injury, young age, and/or delay in seeking medical care, which
      allows for increased secondary injury.

PMID- 15453984
TI  - Inaccurate early assessment of neurological severity in head injury.
AB  - Intubation, which requires sedation and myorelaxants, may lead to inaccurate
      neurological evaluation of severely head-injured patients. Aims of this study
      were to describe the early clinical evolution of traumatic brain injured (TBI)
      patients admitted to intensive care unit (ICU), to identify cases of over
      estimated neurological severity, and to quantify the risk factors for this over
      estimation. A total of 753 TBI patients consecutively admitted to ICU of three
      academic neurosurgical hospitals (NSH) were assessed. Cases whose severity was
      potentially over-estimated were identified by four criteria and indicated as
      "mistakenly severe" (MS): (1) no surgical intracranial masses; (2) could not
      follow commands at neurological assessment; (3) were dismissed from the ICU in <
      or =3 days to a regular ward; and (4) had regained the ability to obey commands.
      A total of 675 patients were intubated and/or sedated-paralyzed at the post
      stabilization evaluation. In all, 304 patients had surgically treated
      intracranial masses. Among the 449 non-surgical cases, 58 patients fulfilling the
      criteria for MS were identified. The main features distinguishing MS from truly
      severe cases were younger age, higher Glasgow Coma Scale (GCS) score at all time
      points, Marshall classification of Computerized Tomographic (CT) scan mostly
      Diffuse Injury I and II, fewer pupillary abnormalities, and a lower frequency of
      hypoxia, hypotension, and extra-cranial injuries. In a certain proportion of non
      surgical TBI patients, mostly intubated and sedated, neurological examination is
      difficult and severity can be over-estimated. Risk factors for this inaccurate
      evaluation can be identified, and clinical decisions should be based on further
      examination.

PMID- 15453985
TI  - Differential gene expression in hippocampus following experimental brain trauma
      reveals distinct features of moderate and severe injuries.
AB  - Microarray technology was employed to determine the differential pattern of gene
      expression within the hippocampus as a result of traumatic brain injury (TBI).
      The validity of the microarray data was confirmed using real-time RT-PCR.
      Following either moderate or severe lateral fluid percussion injury, rats were
      studied 0.5, 4, and 24 h after injury. In general, animals exhibited mRNA up or
      down regulation of approximately 10% of the genes studied. However, it was clear
      that the pattern of gene expression was influenced by both the severity of injury
      and the time after injury at which animals were studied. For example, genes
      encoding molecules for cellular signaling, synaptic plasticity, metabolism, ion
      channels and transporters were up regulated following severe injury, but down
      regulated following moderate injury. Furthermore, moderate injury was associated
      with an increasing number of responsive genes as a function of time post-injury.
      However, animals sustaining a severe level of injury exhibited decreasing number
      of responsive genes during the same post-injury period. The different patterns of
      gene expression between injury severity and across time after the insult suggests
      that the pathophysiological cascade induced by TBI is accompanied by a molecular
      response which, like the other aspects of the cellular response for survival, may
      indicate a "molecular window" that may offer an opportunity for therapeutic
      interventions involving gene therapy. Our results also suggest that fundamentally
      different pathophysiological processes or cascades may be induced by different
      severities of injury.

PMID- 15453986
TI  - The protective effect of cyclosporin A upon N-acetylaspartate and mitochondrial
      dysfunction following experimental diffuse traumatic brain injury.
AB  - Pre- and post-injury Cyclosporin A (CsA) administration has shown neuroprotective
      properties by ameliorating mitochondrial damage. The aim of this study was to
      assess the effect of CsA upon N-acetylaspartate (NAA) reduction and ATP loss, two
      sensitive markers of mitochondrial dysfunction and bioenergetic impairment. Adult
      male Sprague-Dawley rats were exposed to impact acceleration traumatic brain
      injury (2 m/450 g) and randomized into the following experimental groups:
      intrathecal CsA/vehicle treated (n = 12), intravenous CsA/vehicle treated (n =
      18) and sham (n = 12). Intrathecal treatment consisted of post-injury (30 min)
      cisternal bolus of CsA or Vehicle (0.15 mL, 10 mg/kg). Intravenous administration
      consisted of 30 min post-injury continuous 1 hour infusion of either 20 or 35
      mg/kg CsA or Vehicle. Quantitative HPLC analysis of whole brain samples was
      performed 6 h post-injury for levels of NAA and ATP. Following intrathecal
      delivery CsA demonstrated significant neuroprotection blunting a 30% NAA
      reduction (p < 0.001) and restoring 26% of the ATP loss (p < 0.005). The 20 mg/kg
      intravenous dose failed to ameliorate the biochemical damages while the 35 mg/kg
      dosage showed 36% NAA recovery and 39% ATP restoration (p < 0.001). In
      conclusion, CsA is capable of restoring ATP and blunting NAA reduction.
      Intravenous infusion of 35 mg/kg appears to be the optimal therapeutic strategy
      in this model. These findings contribute to the notion that CsA achieves
      neuroprotection, preserving mitochondrial function, and provides a rationale for
      the assessment of CsA in the clinical setting where MR spectroscopy can monitor
      NAA and ATP in brain-injured patients.

PMID- 15453987
TI  - Oxygen free radical-dependent activation of extracellular signal-regulated kinase
      mediates apoptosis-like cell death after traumatic brain injury.
AB  - Mitogen-activated protein kinase (MAPK) cascades are membrane-to-nucleus
      signaling modules that recently have been implicated as mediators of cellular
      injury. In this study, we investigated the involvement of the MAP kinase p44/p42
      (extracellular signal-regulated kinase [ERK1/2]) in traumatic brain injury (TBI)
      in rats. There was a strong increase in activated, phosphorylated ERK 1/2 (p-ERK
      1/2) protein at 10 min up to 24 h after the injury. Expression of p-ERK occurred
      in cells identified as neurons, astrocytes, and microglia. Most of the cells
      expressing p-ERK were TUNEL positive at later time points. Treatment with the MEK
      inhibitor U0126 or the free radical scavenger S-PBN, both with neuroprotective
      properties in TBI, attenuated the early activation of ERK and resulted in less
      activation of caspase-3 and subsequent DNA fragmentation. Post-treatment with
      U0126 resulted in a significant decrease (-60%) in cortical cavity size and
      cortical atrophy at 2 weeks after trauma. Overall, the results suggest that ERK
      activation is initiated by increased oxygen radical activity and that
      overactivation of ERK sets off secondary cell death mechanisms in TBI. Clinical
      studies are warranted to evaluate the concept of MEK inhibition in head-injured
      patients.

PMID- 15453988
TI  - Cell-specific upregulation of survivin after experimental traumatic brain injury
      in rats.
AB  - In this study, we examined the expression and cellular localization of survivin
      and proliferating cell nuclear antigen (PCNA) after controlled cortical impact
      traumatic brain injury (TBI) in rats. There was a remarkable and sustained
      induction of survivin mRNA and protein in the ipsilateral cortex and hippocampus
      of rats after TBI, peaking at five days post injury. In contrast, both survivin
      mRNA and protein were virtually undetectable in craniotomy control animals.
      Concomitantly, expression of PCNA was also significantly enhanced in the
      ipsilateral cortex and hippocampus of these rats with similar temporal and
      spatial patterns. Immunohistochemistry revealed that survivin and PCNA were co
      expressed in the same cells and had a focal distribution within the injured
      brain. Further analysis revealed a frequent co-localization of survivin and GFAP,
      an astrocytic marker, in both the ipsilateral cortex and hippocampus, while a
      much smaller subset of cells showed co-localization of survivin and NeuN, a
      mature neuronal marker. Neuronal localization of survivin was observed
      predominantly in the ipsilateral cortex and contralateral hippocampus after TBI.
      PCNA protein expression was detected in both astrocytes and neurons of the
      ipsilateral cortex and hippocampus after TBI. Collectively these data demonstrate
      that the anti-apoptotic protein survivin, previously characterized in cancer
      cells, is abundantly expressed in brain tissues of adult rats subjected to TBI.
      We found survivin expression in both astrocytes and a sub-set of neurons. In
      addition, the expression of survivin was co-incident with PCNA, a cell cycle
      protein. This suggests that survivin may be involved in regulation of neural cell
      proliferative responses after traumatic brain injury.

PMID- 15453989
TI  - Comparison of tetrahydrobiopterin and L-arginine on cerebral blood flow after
      controlled cortical impact injury in rats.
AB  - The purpose of this study was to compare the effects of L-arginine and
      tetrahydrobiopterin administration on post-traumatic cerebral blood flow (CBF)
      and tissue levels of NO in injured brain tissue. Rats were anesthetized with
      isoflurane. Mean blood pressure, intracranial pressure, cerebral blood flow using
      laser Doppler flowmetry (LDF) and brain tissue nitric oxide (NO) concentrations
      were measured prior to, and for 2 h after a controlled cortical impact injury. L
      arginine, 300 mg/kg, tetrahydrobiopterin, 10 mg/kg, or equal volume of saline was
      given at 5 min after injury. In the saline-treated animals, LDF decreased to 34
      +/- 4% of baseline values after injury. NO concentration also decreased by
      approximately 20 pmol/ml from baseline values. L-arginine and tetrahydrobiopterin
      administration both resulted in a significant preservation of tissue NO
      concentrations and an improvement in LDF, compared to control animals given
      saline. These studies demonstrate that tetrahydrobiopterin administration has a
      beneficial effect on cerebral blood flow that is similar to L-arginine
      administration, and may suggest that depletion of tetrahydrobiopterin plays a
      role in the post-traumatic hypoperfusion of the brain.

PMID- 15453990
TI  - Altered NO function contributes to impairment of uPA and tPA cerebrovasodilation
      after brain injury.
AB  - Urokinase (uPA) and tissue plasminogen activator (tPA) are serine proteases
      implicated in fibrinolysis, but their role in the regulation of the
      cerebrovascular response to brain trauma has not been investigated. This study
      was designed to (1) characterize the cerebrovascular activity of uPA and tPA, (2)
      investigate the role of nitric oxide (NO) in uPA and tPA vascular activity, and
      (3) characterize the effect of fluid percussion brain injury (FPI) on vascular
      responses to uPA and tPA. The closed cranial window technique in chloralose
      anesthetized newborn pigs was used to measure pial artery diameter and collect
      CSF for radioimmunoassay (RIA) of cGMP concentration. Topical uPA (10(-9), 10(-7)
      M) elicited pial artery dilation that was blunted by the NO synthase inhibitor, L
      NNA (10(-6) M) (8 +/- 1% and 13 +/- 1 vs. 3 +/- 1% and 7 +/- 2%, respectively).
      Vasodilation in response to uPA was associated with an increase in CSF cGMP
      concentration (645 +/- 20, 865 +/- 39 and 1088 +/- 33 fmol/mL cGMP for control,
      uPA 10(-9), 10(-7) M, respectively). Similar data were obtained for tPA. Pial
      artery dilation to uPA was blunted following FPI (7 +/- 1% and 12 +/- 1% vs. 3 +/
      1% and 6 +/- 1%, respectively), while uPA-associated release of cGMP was blocked
      (677 +/- 45, 909 +/- 53, and 1110 +/- 55 vs. 283 +/- 10, 316 +/- 18, and 333 +/-
      26 fmol/mL for control, uPA 10(-9), 10(-7) M before and after FPI, respectively).
      Similar data were obtained for tPA. These data show that uPA and tPA produce pial
      artery dilation in an NO-dependent manner. FPI blunted uPA and tPA induced pial
      artery dilation as well as the associated release of cGMP. These data suggest
      therefore that altered NO function contributes to the impairment of uPA and tPA
      cerebrovasodilation after brain injury.

PMID- 15453991
TI  - Cerebral pressure autoregulation is intact and is not influenced by hypothermia
      after traumatic brain injury in rats.
AB  - In head-injured patients and experimental traumatic brain injury (TBI), important
      cerebrovascular abnormalities include decreases in cerebral blood flow (CBF) and
      impairment of cerebral pressure autoregulation. We evaluated CBF and pressure
      autoregulation after fluid percussion injury (FPI) and hypothermia in rats with
      the hypothesis that hypothermia would ameliorate changes in posttraumatic CBF.
      Male Sprague-Dawley rats, intubated and mechanically ventilated, were prepared
      for parasagittal FPI (1.8 atm) and laser Doppler CBF flow (LDF) measurement. The
      abdominal aorta was cannulated for rapid removal and reinfusion of blood.
      Baseline autoregulatory testing in all groups consisted of LDF measurements at
      normothermia and a mean arterial pressure (MAP) of 100 mm Hg, followed by
      randomly ordered changes of MAP to 80, 60, and 40 mm Hg. Animals were then
      randomized to one of five groups: normothermic control without FPI; normothermia
      with FPI; hypothermic control (32 degrees C) without FPI; hypothermia initiated
      before FPI; and hypothermia initiated immediately after FPI injury. For each
      group, a complete, randomly ordered autoregulatory sequence was performed at 30
      and 60 min after FPI or sham TBI. In a second study, rats were prepared
      identically, maintained at normothermic temperatures and autoregulation was
      tested before and after TBI using a set of randomly ordered levels of hypotension
      or using progressive reductions in MAP (i.e., 80, 60, 40 mm Hg) with the
      hypothesis that the technical manner and timing of decreasing of the blood
      pressure would effect CBF after TBI. Due to high acute mortality, the group in
      which hypothermia was induced before FPI was excluded from the analysis. At
      baseline, autoregulation was similar in all groups. There was no change in CBF or
      autoregulation in the normothermic control group at 30 and 60 min. In the other
      groups at 30 and 60 min, there was a similar, statistically significant decrease
      in absolute CBF (i.e., a decrease of 27-57% of baseline values), but pressure
      autoregulation was intact except at the lowest blood pressure tested at 60 min,
      where there was a slight improvement in the hypothermic group. Thus, in these
      experiments, absolute CBF decreased with hypothermia and FPI, while neither
      hypothermia nor FPI significantly altered autoregulation. In the second study,
      autoregulatory function was not different before TBI when comparing random and
      sequential blood pressure changes, but, when comparing the groups after TBI at
      the 60 mm Hg blood pressure level, CBF was significantly lower in the sequential
      group than in the random order group. This suggests that the mechanism of
      creating hypotension, whether random or sequential, significantly affects the
      measurement of CBF and autoregulation after TBI in rats.

PMID- 15453992
TI  - Transplantation of Schwann cells and olfactory ensheathing glia after spinal cord
      injury: does pretreatment with methylprednisolone and interleukin-10 enhance
      recovery?
AB  - Methylprednisolone (MP) and interleukin-10 (IL-10) are tissue protective acutely
      after spinal cord injury (SCI); their combination offers additive protection
      (Takami et al., 2002a). Our study examined if acute administration of MP (30
      mg/kg i.v. at 5 min, and 2 and 4 h after injury) and IL-10 (30 mg/kg i.p. at 30
      min after injury) increases the efficacy of Schwann cell (SC) or SC plus
      olfactory ensheathing glia (SC/OEG) grafts transplanted into rat thoracic cord 1
      week after contusive injury. Efficacy was determined by histology, anterograde
      and retrograde tracing, immunohistochemistry for gliosis and specific nerve
      fibers, and several behavioral tests. Administration of MP/IL-10 or SC or SC/OEG
      transplantation significantly increased the total volume of a 9-mm segment of
      cord encompassing the injury site at 12 weeks. The combination of either SC or
      SC/OEG transplantation with MP/IL-10 most significantly reduced cavitation. The
      individual treatments all significantly increased the volume of normal-appearing
      tissue compared to injury-only controls; however, significant decreases in the
      volume of normal-appearing tissue were seen when MP/IL-10 and cell grafts were
      combined compared to MP/IL-10 alone. SC/OEG grafts were effective in promoting
      serotonergic fiber growth into the graft and led to more reticulospinal fibers
      caudal to the graft; combination with MP/IL-10 did not further increase fiber
      number. Only the combination of MP/IL-10 with SC/OEG transplants significantly
      improved gross locomotor performance (BBB scores) over injury-only controls.
      MP/IL-10 given prior to SC-only transplants, however, worsened behavioral
      outcome. Because beneficial effects of MP/IL-10 were not always additive when
      combined with cell transplantation, we need to understand (1) how tissue
      protective agents may transform the milieu of the injured spinal cord to the
      benefit or detriment of later transplanted cells and (2) whether neuroprotectants
      need to be re-administered at the time of cell grafting or less invasive
      transplantation techniques employed to reduce damage to tissue spared by an
      earlier protection strategy.

PMID- 15453993
TI  - Higher calpastatin levels correlate with resistance to calpain-mediated
      proteolysis and neuronal apoptosis in juvenile rats after spinal cord injury.
AB  - While the average age for patients admitted with spinal cord injury is 32 years,
      patients under the age of 16 account for 5% of spinal cord injured persons. For
      these younger patients, an increased mortality up to 24 h post-injury has been
      reported, however, survivors may regain more function than their adult
      counterparts, suggesting that age may play a role in injury tolerance. While the
      use of growth factors as a therapy for spinal cord injury is well researched, the
      response of the developing cord to secondary injury has not been thoroughly
      investigated. Following spinal cord injury, Ca(2+) influx can activate enzymes
      such as calpain, a Ca(2+)-dependent protease, which plays a role in the
      pathogenesis of spinal cord injury in rats. The present investigation revealed
      that following spinal cord injury, calpain upregulation was significantly less
      (15.3%) in the 21-day-old rats than in either 45-day-old (70%) or 90-day-old
      (99.6%) rats, as shown by Western blot and in situ immunofluorescent studies.
      Expression of the endogenous calpain inhibitor, calpastatin, was significantly
      higher in juvenile rats than adult rats. Juvenile rats with spinal cord injury
      also showed a reduced Bax:Bcl-2 ratio (4:1 vs. 6:1), reduced caspase-3 staining,
      reduced myelin loss (3% vs. 18%), and less neuronal DNA damage, as compared to
      older rats. These results suggest that increased calpastatin levels found in
      juvenile rats muted calpain activity and neuronal apoptosis, following spinal
      cord injury.

PMID- 15453994
TI  - Poly(ADP-ribose) polymerase activity contributes to peroxynitrite-induced spinal
      cord neuronal cell death in vitro.
AB  - Peroxynitrite, which has been implicated in secondary neuronal damage resulting
      from spinal cord injury, is capable of mediating several toxic interactions
      including inducing DNA strand breaks and activating the nuclear enzyme, poly (ADP
      ribose) polymerase (PARP). In the present study we have tested the hypothesis
      that peroxynitrite-induced cell death in spinal cord injury is due to activation
      of PARP. Initially we examined whether peroxynitrite exerts toxic effects on
      primary cultures of spinal cord neurons and then determined whether the spinal
      cord neuronal cell death triggered by peroxynitrite was associated with PARP
      activation. Peroxynitrite dose-dependently reduced the viability of spinal cord
      neurons in vitro. Furthermore, peroxynitrite exposure markedly increased the
      number of DNA strand breaks in primary spinal cord neurons, resulting in
      activation of PARP. To identify whether PARP activation plays a direct role in
      peroxynitrite-induced neurotoxicity we assessed the effects of the PARP
      inhibitors, nicotinamide, 3-aminobenzamide and 5-iodo-6-amino-1,2 benzopyrone on
      cell viability in spinal cord neurons exposed to peroxynitrite. The presence of
      the PARP inhibitors in the cultures not only inhibited peroxynitrite-induced PARP
      activity in spinal cord neurons but also protected the cells from the deleterious
      actions of peroxynitrite. Therefore, our results demonstrate that peroxynitrite
      exerts toxic effects on spinal cord neurons in vitro at least in part through a
      PARP-dependent pathway.

PMID- 15453997
TI  - Sleep disturbance after rapid ascent to moderate altitude among infants and
      preverbal young children.
AB  - Rapid ascent to high altitude is known to result in sleep disturbances among
      adults. No data exist regarding the effects of altitude exposure on sleep in
      children. The objective of this study was to determine the effect of rapid ascent
      to moderate altitude on sleep in infants and young children. In this prospective
      study, each child served as his or her own control. Each subject was studied over
      7 days and nights. On days 1 and 2, children were studied at home (1601 m), day 3
      at a hotel without ascent (travel control), day 4 at home, days 5 and 6 at a
      hotel after ascent (3109 m), and day 7 at home. Since increased motion is a
      characteristic of sleep disturbance among infants and young children, continuous
      measurements of motion were made using an ankle-mounted Actigraph. Thirty
      children, 17 girls and 13 boys, with a median age of 16.5 months (range = 4 to 33
      months) participated in the study. Significant changes in the activity counts,
      reflecting a sleep disturbance during nocturnal sleep, were noted between the
      travel control night (20.9 +/- 1.9) and the first night at altitude (29.4 +/-
      2.5): p < 0.01. This sleep disturbance is most significant during the first night
      at altitude and may be similar to sleep disturbance with altitude exposure seen
      in adults.

PMID- 15453998
TI  - Physiological basis for recommendations regarding exercise during pregnancy at
      high altitude.
AB  - Although exercise during pregnancy has been shown to be safe and is now
      recommended by the American College of Obstetricians and Gynecologists and the
      Society of Obstetricians and Gynaecologists of Canada for all healthy women,
      little is known about the combined effects of high altitude and exercise during
      pregnancy. Due to a paucity of experimental data, recommendations regarding
      exercise during pregnancy at elevations >/=1600 m must be based on synthesis of
      available information regarding the independent effects of high altitude and
      exercise on uteroplacental oxygen delivery. Maternal hyperventilation and
      elevated blood hemoglobin concentration maintain resting arterial oxygen content
      at or above sea-level values. During exercise, however, arterial hemoglobin
      saturation falls, lowering the oxygen content. Resting uterine artery blood flow
      is lower in residents at 3100 m than at 1600 m, and flow is likely to decrease
      further during exercise, in proportion to the intensity and duration. The
      combined reduction in arterial oxygen content and uterine artery flow suggest
      that fetal oxygen delivery is compromised during exercise at altitude. Anemia,
      which should be defined according to altitude-adjusted criteria, will further
      diminish oxygen delivery. Clinicians may wish to monitor patient hemoglobin
      concentration more frequently and adopt a more conservative stance regarding
      exercise during pregnancy for both residents and visitors of altitudes >/=1600 m.

PMID- 15453999
TI  - Prediction of susceptibility to acute mountain sickness by SaO2 values during
      short-term exposure to hypoxia.
AB  - Prediction of the development of acute mountain sickness (AMS) in individuals
      going to high altitudes is still a matter of debate. Whereas some studies found
      that subjects with a blunted hypoxic ventilatory response (HVR) are predisposed
      to AMS, others did not. However, the HVR has often been determined under very
      acute (5 to 10 min) isocapnic hypoxia without consideration of the subsequent
      hypoxic ventilatory decline (HVD), and the assessment of AMS susceptibility was
      based on a single altitude exposure. Therefore, the aim of the present study was
      to evaluate the relationship between the individual arterial oxygen saturation
      (Sa(O2)) after a 20- to 30-min exposure to poikilocapnic hypoxia and the AMS
      susceptibility based on repeated observations. A total of 150 healthy male and
      female mountaineers (ages: 42 +/- 13 yr), 63 of whom had known susceptibility to
      AMS and 87 of whom never suffered from AMS, were exposed to various degrees of
      normobaric and hypobaric hypoxia. Sa(O2) values were taken by finger
      pulseoximetry after 20 to 30 min of hypoxic exposure. Sa(O2) values after 20 to
      30 min of hypoxia were on average 4.9% lower in subjects susceptible to AMS than
      in those who were not. Logistic regression analysis revealed altitude-dependent
      Sa(O2) values to be predictive for AMS susceptibility. Based on the derived
      model, AMS susceptibility was correctly predicted in 86% of the selected
      individuals exposed to short-term hypoxia. In conclusion, Sa(O2) values after 20
      to 30 min of exposure to normobaric or hypobaric hypoxia represent a useful tool
      to detect subjects highly susceptible to AMS.

PMID- 15454000
TI  - Pulse oximetry in the diagnosis of acute mountain sickness.
AB  - Acute mountain sickness (AMS) is a common condition in individuals who travel to
      altitudes over 2000 m. While AMS is an important public health problem, no
      measurements can reliably support or predict the diagnosis with any degree of
      confidence. We therefore set out to study whether pulse oximetry data are
      associated with AMS. We studied 169 subjects who had recently arrived by foot at
      3080 m. Subjects completed a demographic survey, which collected data on ascent
      profiles and AMS symptoms. Resting arterial oxygen saturation and pulse rate were
      then measured using finger pulse oximetry. Forty-six subjects (27%) had AMS,
      using the Lake Louise score. Only pulse rate was significantly associated with
      the presence of AMS (OR: 1.4; 95% CI, 1.1 to 1.9; p < 0.05, backwards stepwise
      logistical regression). A trend showed worse AMS diagnoses were associated with
      higher mean pulse rates (p < 0.05, ANOVA linear weighted analysis). While some
      previous studies have shown an association between decreased oxygen saturation
      and acute mountain sickness at altitude, our results did not demonstrate such an
      association. The utility of pulse oximetry remains limited in the diagnosis of
      AMS. We recommend further study to determine the possible utility of pulse rate
      in the diagnosis and prediction of AMS.

PMID- 15454001
TI  - Severity and pattern of injury in survivors of alpine fall accidents.
AB  - Few data are available on the medical aspects of fall accidents in mountainous
      terrain. Therefore, we report the severity and pattern of injury in 97 survivors
      of a major fall in Alpine terrain. Twenty-eight of 97 victims (29%) had severe or
      critical multisystem trauma, with an injury severity score >/=14, the incidence
      increasing to 23 out of 28 (82%) in individuals with falls exceeding 50 m.
      Fractures of the extremities and the sacropelvic region (n = 55) were the most
      common injuries. Seventeen of 21 spine fractures (81%) occurred in the
      thoracolumbar region. Rib fractures were found in 17 victims, in eight of them
      (47%) with an accompanying pneumothorax. Critical head trauma with a Glasgow Come
      Scale below 9 was rather uncommon (n = 6); abdominal visceral injuries were rare
      (n = 2). The pattern of injury observed in our study suggests a feet- or side
      first body position at impact in the majority of individuals surviving Alpine
      fall accidents. Furthermore, it indicates a direct impact, rather than
      deceleration type mechanism of injury. Because of the high incidence of severe
      multisystem trauma, major fall in Alpine terrain should be used as triage
      criterion for the dispatch of an advanced trauma life support unit and direct
      transfer of the victim to a trauma center. Considering the high incidence of
      fractures, measures for adequate immobilization and analgesia will generally be
      necessary before the difficult evacuation from the site of the accident can be
      started.

PMID- 15454002
TI  - Energy intake during a typical Himalayan trek.
AB  - People taking part in commercial treks are exposed to high altitude (HA) while
      eating ad libitum, a situation that has been related to under eating and body
      weight loss. We investigated this phenomenon in westerners taking part in a
      typical Himalayan trek. Body weight, energy intake (EI), macronutrient
      composition of the diet, and acute mountain sickness symptoms (AMS) were measured
      in seven healthy individuals (aged 45 +/- 12 yr and BMI 24.6 +/- 4.4 kg/m(2))
      during a 19-day trek to Makalu Base Camp. Comparisons were made between three
      periods of the trek: a 5-day climb below 2500 m (low altitude 1: LA1), an 8-day
      period between 3500 m and 5200 m (high altitude: HA), and a 4-day descent below
      2500 m (low altitude 2: LA2). Body weight was significantly reduced at the end of
      the trek (p < 0.01). A decrease in total EI was observed at HA (p < 0.05). This
      was followed by an increase in EI upon return to LA2 (p < 0.001). Neither EI nor
      macronutrient composition of the diet was associated with the presence of AMS. In
      conclusion, a decrease in EI was observed in HA, which does not seem to be
      macronutrient specific.

PMID- 15454003
TI  - Prelude to Everest: Alexander M. Kellas and the 1920 high altitude scientific
      expedition to Kamet.
AB  - Following his untimely death due to illness during the early stages of the first
      Mount Everest Reconnaissance Expedition in 1921, Alexander M. Kellas has received
      relatively little attention in either mountaineering or scientific literature. He
      remains an obscure figure despite his noteworthy contributions to high altitude
      physiology and exploration. He can be considered not only one of the finest
      exploratory Himalayan mountaineers in history, but also the first person to apply
      state-of-the-art knowledge of high altitude physiology to field investigations at
      altitudes over 6000 m. By the time of his death, it is extremely likely that
      Kellas had spent more time above 6000 m than anyone on Earth, undertaking no
      fewer than eight Himalayan expeditions between 1907 and 1921. This article
      revisits and examines in some detail the most ambitious high altitude
      physiological field study undertaken through the second decade of the 20th
      century, A. M. Kellas and Henry T. Morshead's 1920 Kamet Expedition. This
      undertaking by Kellas and Morshead was unique because it specifically emphasized
      investigation of the practical difficulties inherent in climbing at very high
      altitudes. During this endeavor, Kellas carried out the first rigorous tests of
      the value of supplementary oxygen for climbing at high altitude. The results of
      the field studies conducted during the 1920 Kamet Expedition provided strong
      support for the use of supplementary oxygen at high altitude. However, after
      Kellas died on the approach march to Everest the following year, the British
      mountaineering establishment did not again have a similar proponent or exponent
      of extreme altitude field research until physiologist Griffith Pugh once again
      took up the challenge in the early 1950s.

PMID- 15454004
TI  - Altitude-induced hypertension in bi-landers.

PMID- 15454005
TI  - [Immediate loading of dental implants in partialful edentulous and edentulous
      jaws].
AB  - OBJECTIVE: To investigate the clinical feasibility and technical characteristics
      of immediate loading and to access the short-term clinical results of treatment.
      METHODS: This study included 3 completely edentulous patients and 24 patients who
      were partially edentulous from March 1999 to December 2003. 21 implants were
      immediately loaded and provided support for mandibular overdenture for 3 fully
      edentulous patients. 30 implants were placed in 21 partially edentulous patients
      and implants were immediate loaded in edentulous mandibular providing support for
      fixed provisional prosthesis within 6 months. Then, metal-ceramic crowns were
      completed. All patients were followed up by 1, 3, 6, 12 months and the patients
      were checked every 12 months. RESULTS: A total of 42 implants were loaded
      immediately. From March 1999 to December 2003, no implants were lost during
      follow-up (range 3 to 49 months, mean of 28 months). No infections, nerve or
      sinus damage or other sequelae occurred. No implants exhibited peri-implant
      radiolucencies. Moreover, immediate loading seems to increase the ossification of
      the alveolar bone around endosseous implants. Patients were satisfied with the
      treatment. CONCLUSIONS: The data and the experience described in this study
      indicate that immediate loading with restorations using appropriate surgical and
      restorative techniques can predicate the completely edentulous and partially
      edentulous mandible in some cases. Further study is needed to determine the long
      term result of immediately loaded implants.

PMID- 15454006
TI  - [Using platelet-rich plasma (PRP) to improve bone regeneration in implant bone
      defect].
AB  - OBJECTIVE: To evaluate the result of bone regeneration due to using PRP in
      combination with beta-TCP in bone defect adjacent to oral implantation. METHODS:
      Ten patients (6 males, 4 females, with an average age of 49.6 years) participated
      in this study. Seven of them underwent maxillary sinus augmentations, and 3
      underwent GBR for peri-implant bone defects. PRP + beta-TCP was used in 4 cases
      and beta-TCP in other 6 as control. X-ray examinations were carried out prior to
      operation and in 1 week, at 3 months, 6 months after operation. After 4 - 6
      months, 3 biopsy specimens were obtained at the time of the second stage
      operation in each group. RESULTS: Bone grafts healed well without any infection
      in all cases. Radiographs showed that bone grafts integrated together with the
      bone. The histological result showed that new bone was formed among particles of
      beta-TCP in both groups, but in PRP + beta-TCP group denser and better arranged
      woven bone was observed, and more new bone was formed into the micropores of the
      particles. CONCLUSIONS: The result in this study implied that PRP in combination
      with beta-TCP can improve bone regeneration in bone defect adjacent to oral
      implantation.

PMID- 15454007
TI  - [The inhibitory effect of human endostatin gene on tumor growth of tongue
      squamous cell carcinoma].
AB  - OBJECTIVE: To investigate the expression of transfected human endostatin (hES)
      gene in tongue squamous cell carcinoma (TSCC) and its inhibitory effects on the
      growth of tumor cells in vivo. METHODS: Lipofectamine-mediated hES gene was
      transferred into Tca8113 cells, selected with Blasticidin S; The stable
      transfected cells were inoculated in BALB/c mice, and then the growth of
      xenografts was observed. The hES and vascular endothelial growth factor (VEGF)
      protein expression of xenografts was detected by S-P immuno-histochemical assay.
      We also detected the microvessel density (MVD) of xenografts with Weidern's
      method and apoptotic index of the tumor cells by flow cytometry (FCM). RESULTS:
      The hES protein expression of xenografts in experimental group was significantly
      higher than that in control group (P < 0.01), while the expression of VEGF
      protein was on the other way round (P < 0.01). MVD counting of xenografts in
      experimental group was lower than that in control group (P < 0.01). The mean
      apoptotic level of the tumor cells in control group was also lower than in
      experimental group (P < 0.01). In addition, the inhibitory rate to growth of
      xenografts induced by hES transfection was 78.9%. CONCLUSIONS: hES gene can be
      transferred into TSCC cells and then induce corresponding protein expression
      efficiently in xenograft model, resulting in significantly inhibitory effects on
      the xenografts in vivo.

PMID- 15454008
TI  - [Study of the relative factors of the biological behavior of pleomorphic adenoma
      in parotid].
AB  - OBJECTIVE: To study the growth way of parotid pleomorphic adenoma and the
      relative factors. METHODS: The histological slides of 97 cases of the primary
      parotid pleomorphic adenoma were examined for the state of intra-capsule
      infiltration and extra-infiltration. The relative relationships between the
      infiltration state and the histological type, relative amount of various
      components, size and course of the tumor were analysed to investigate the growth
      way and relative factors. RESULTS: 1. There were more chances to develop
      infiltration of tumor in which the major content was epithelium. The tumor was
      severer with the increasing of epithelium, and decreasing of mucous content and
      elongation of course of the disease. 2. The limitation of the extra-envelop
      infiltration and budding was 0.085 - 0.210 mm, so, the boundary of partial
      parotidectomy should be away from the 1 cm envelop. CONCLUSION: The growth way of
      parotid pleomorphic adenoma is related to the histological types and characters,
      relative amount of various components and the course of the tumor.

PMID- 15454009
TI  - [Prospective study on results of the surgical crown lengthening and its
      associated factors].
AB  - OBJECTIVE: To observe the results of surgical crown lengthening procedure and the
      factors which affected the success of the surgery. METHODS: Crown lengthening
      surgery was performed on 27 teeth. The distance between margin of tooth and bone
      crest (MT-B) was obtained greater than 4 mm during the surgeries on 10 teeth
      which were considered as satisfying group. The other 17 teeth were as temporized
      group with MT-B < or = 3 mm. The position of the tooth margin was evaluated
      before surgery, immediately after suturing, and at 4 - 6 weeks after surgery. The
      occlusal force and tooth mobility were measured immediately after restoration, at
      3 and 6 months after surgery. RESULTS: MT-B was obtained > or = 4 mm and all
      margins and sites of the teeth were exposed in satisfying group (10/10). At least
      1 site with MT-B < 3 mm in temporized group in which there still were 11 sites
      (16%) in 5 teeth (29%) with subgingival tooth margin at 4 - 6 weeks after
      surgery. There were more teeth showing increased mobility in temporized group
      (12/17) than in satisfying group (1/10) after surgery (P < 0.05). The occlusal
      force of the teeth after surgery and restoration in temporized group was
      significantly lower than that of their counterpart teeth (P < 0.01), but it was
      not the case in satisfying group (P > 0.05). CONCLUSIONS: It is suggested that
      ideal exposure of tooth margin could be obtained if 4 mm from tooth margin to
      alveolar crest could be created during the crown lengthening surgery. The teeth
      both with 4 - 5 mm subgingival margin sites and factors limiting surgical
      performance are not the suitable indications for the surgical crown lengthening.

PMID- 15454010
TI  - [Effects of minocycline on biobehavior of human periodontal ligament cells in
      vitro].
AB  - OBJECTIVE: To evaluate the influence of minocycline on the proliferation and
      biosynthesis of human periodontal ligament cells (HPDLCs) in vitro. METHODS:
      Various concentrations of minocycline (1, 5, 20, 100, 500, 2 500 mg/L) were added
      to the medium of cultured HPDLCs respectively. After co-incubated for 2 days,
      cell morphology was observed under reverse microscope, cell proliferation
      activity was assayed using MTT, the total amount of protein was detected with
      Coumassie Bright Blue method and DNA synthesis was measured by (3)H-TdR. RESULTS:
      The presence of minocycline not exceeding 500 mg/L in the medium resulted in no
      morphological change of HPDLCs. Moreover, at a concentration range of 5 to 100
      mg/L, minocycline significantly enhanced the proliferative activity and
      biosynthesis of HPDLCs (P < 0.01). However, higher concentration (2 500 mg/L) not
      only changed cell morphology under microscope, but also significantly inhibited
      cellular activity. CONCLUSIONS: The results suggest that proper doses of
      minocycline could promote biobehavior of HPDLCs, while higher concentrations of
      minocycline had cytotoxic effect which may intervene affect tissue repair and
      regeneration.

PMID- 15454011
TI  - [De novo salivary malignant myoepithelioma: pathologic diagnosis of 19 cases].
AB  - OBJECTIVE: To study the pathological characteristics of salivary malignant
      myoepithelioma with characteristic multinodular architecture. METHODS: To observe
      the histologic and cytologic characteristics of 19 cases of de novo salivary
      malignant myoepithelioma with multinodular growth pattern. Immunohistochemistry
      of calponin, SMA, S-100, GFAP, cytokeratin, PCNA was done on 11 cases and
      ultrastructure was observed on 3 cases. RESULTS: 19 tumors presented
      characteristic multinodular growth pattern, mostly accompanied by central
      necrosis. Neoplastic nests invaded the surrounding normal tissue and tumor cells
      displayed a variety of pleomorphism. Epitheliod cell was the most predominant
      cell type. Tumor-related extracellular matrix formation was revealed among tumor
      cells. Immunohistochemical staining demonstrated that the tumor cells were
      positive for calponin, SMA, S-100, GFAP, AE1/AE3, CKH and PCNA. Myofilaments were
      found in neoplastic cell cytoplasm under the electron microscope. CONCLUSION:
      Histologic and cytologic observation, immunostaining and ultrastructural study
      all supported the myoepithelial and malignant nature of the tumor.

PMID- 15454012
TI  - [Epstein-Barr virus infection in benign lymphoepithelial lesions with malignant
      transformation of salivary glands].
AB  - OBJECTIVE: To examine the role of Epstein-Barr virus (EBV) infection in benign
      lymphoepithelial lesions with malignant transformation of salivary glands.
      METHODS: 2 cases benign lymphoepithelial lesions with focal malignant
      transformation (BLEL-FMT), 14 cases of malignant lymphoepithelial lesion (MLEL)
      and 4 cases of benign lymphoepithelial lesion (BLEL) of salivary glands, 4 cases
      of nonspecific chronic sialadenitis were examined. Sections were cut from the
      paraffin blocks and performed in situ hybridization (ISH) for EBV encoded small
      RNA-1 (EBER-1) using 30-base synthesized oligonucleotide probe and polymerase
      chain reaction (PCR) for BamHI-W regein of EBV DNA (123 bp). RESULTS: In ISH,
      strong signals for EBER-1 were obtained in most of epithelial cell nuclei in
      examined specimens of BLEL-FMT, no matter in benign or malignant areas and in all
      specimens of MLEL (14/14), PCR demonstrated a DNA fragment of 123 kbp in 2 cases
      of BLEL-FMT and 12 cases of MLEL (12/14). In contrast, there were no significant
      ISH/PCR signals in examined BLEL and nonspecific chronic sialadenitis.
      CONCLUSIONS: A few cases of MLEL may arise from BLEL and EBV may plays an
      important role in the pathogenesis of BLEL-FMT of salivary glands.

PMID- 15454013
TI  - [Expression of a disintegrin-like and metalloproteinase protein 8 and 12 in the
      giant cell lesions of jaw].
AB  - OBJECTIVE: To detect the expression of a disintegrin-like and metalloproteinase
      (ADAM) 8 and 12 gene in the giant cell lesions of jaw and to study their effects
      on the histogenesis of cells in these lesions. METHODS: ADAM8 and ADAM12 was
      detected by immunohistochemistry (SP) in 40 paraffin-embedded specimens of
      central giant cell lesions of jaw, 10 peripheral giant cell lesions, 9
      cherubisms, 6 aneurysmal bone cysts. RESULTS: ADAM8 and ADAM12 were positive in
      the cytomembrane and cytoplasm of all multinucleated giant cells and some round
      mononuclear cells of the lesions; ADAM12 was positive for some spindle
      mononuclear stromal cells in central and peripheral giant cell lesions.
      CONCLUSIONS: Multinucleated giant cells probably originated from the fusion of
      the round mononuclear cells, and ADAM8 and ADAM12 were involved in this process.
      In addition, ADAM12 might play a role in the maturation of spindle mononuclear
      stromal cells.

PMID- 15454014
TI  - [Human cytomegalovirus inhibits proliferation of duct epithelial cells of human
      salivary gland].
AB  - OBJECTIVE: To investigate the effects of human cytomegalovirus (HCMV) on the
      proliferation of duct epithelial cells of human salivary gland (HSG). METHODS:
      The expression of proliferating cell nuclear antigen (PCNA) and p53 were studied
      in 11 cases of parotid cytomegalic inclusive disease (PCID) using
      immunohistochemical staining method. The effects of human cytomegalovirus (HCMV)
      on the proliferation of HSG were investigated by MTT method in vitro. The
      expression of PCNA in HSG infected by HCMV was examined using immunocytochemical
      staining and Western blotting. RESULTS: PCNA was expressed weakly in most of
      megalic inclusion cells which were positive for HCMV, while all the megalic
      inclusion cells were p53 negative in all 11 cases of PCID. HCMV inhibited
      proliferation of HSG in vitro in a time dependent and dose dependent manner. Down
      regulation of PCNA was shown in infected cells. CONCLUSION: HCMV inhibits
      proliferation of HSG and down-regulation of PCNA may be an expression of the
      inhibition.

PMID- 15454015
TI  - [Effects of post material on stress distribution in dentine].
AB  - OBJECTIVE: To investigate stress distribution of different material restored post
      cores in dentine and provide a theoretical guidance for clinical use. METHODS: A
      three-dimensional finite element model of maxillary central incisor restored with
      post-core and PFM crown was constructed by SCT scan technology. Based on this
      model, stress distribution in dentine was analyzed before and after post-core
      restorations with 6 different materials, including cast Ni-Cr alloy, cast
      titanium alloy, cast gold alloy, glass fiber reinforced composite, polythene
      fiber reinforced composite, and common composite resin. RESULTS: When the tooth
      was restored with cast Ni-Cr alloy post and PFM crown, the maximum tensile stress
      and Von Mises stress in dentin at post apex increased 152% and 162% respectively,
      compared with a tooth restored only with PFM crown. If polythene fiber reinforced
      composite was used as post material, the stress distribution did not
      significantly change. When the other materials were used for the post, the stress
      distribution changed greatly. The elastic modulus of post-core materials affected
      the stress distribution pattern in dentine. CONCLUSION: The materials with
      elastic modulus similar to that of dentin, such as polythene fiber reinforced
      composite, may be suitable for post restoration.

PMID- 15454016
TI  - [The experimental study on sol-gel technique of coating titanium].
AB  - OBJECTIVE: The aim of this study was to establish sol-gel technique of coating
      titanium on the surface of Ni-Cr alloy (PFM) in order to enhance corrosion
      resistance and reduce corrosive rate in oral cavity. METHODS: The sol-gel
      technique included four steps: (1) pre-treatment; (2) preparation of sol; (3)
      coating; (4) heat treatment. Elements on the surface of Ni-Cr alloy were analyzed
      with X-ray photoelectron spectroscopy. RESULTS: After coating Ti, the surface of
      Ni-Cr alloy looked light golden without particles, blisters and fragments.
      Besides Ni and Cr, titanium was found on surface of Ni-Cr alloy after coating.
      With Ar(+) ion carving-corrosion figure, the thickness of titanium was about 20 -
      80 microm. CONCLUSION: With sol-gel technique, titanium could be coated on the
      surface of Ni-Cr alloy.

PMID- 15454017
TI  - [Study on the metabolism of cartilage matrix by the chondrocytes in
      osteoarthritic condylar cartilage].
AB  - OBJECTIVE: To study the characteristics of cellular metabolism of mandibular
      condylar chondrocytes in repairing state of osteoarthrosis and investigate its
      role in the pathogenesis of the disease. METHODS: Temporomandibular joint
      osteoarthrosis model of rabbits was created by the partial resection of joint
      disc and confirmed with histological diagnosis. The chondrocytes were harvested
      from osteoarthritic condylar cartilage in the repairing state and cultured in
      vitro under the monolayer culture condition. The cellular expression of
      cartilaginous matrix protein, collagenase and growth factors between the
      osteoarthritic chondrocytes and the normal controls were measured with RT-PCR
      technique to outline the basic feature of the osteoarthritic cells. RESULTS: The
      cultured cells were confirmed as chondrocytes with their ability of expression of
      collagen type II and Aggrecan. In the reactive repairing state of osteoarthrosis,
      the chondrocytes showed the imbalance of expression of ECM proteins, and
      increased expression of collagenase and endogenous growth factors such as IGF-1
      and TGF-beta1. CONCLUSIONS: This study found the active anabolism of the
      chondrocytes within the osteoarthritic condylar cartilage and the imbalance
      synthesis of cartilage matrix. These repairing attempts by the osteoarthritic
      chondrocytes may be impossible to restore the primary homeostasis within the
      condylar cartilage.

PMID- 15454018
TI  - [Effect of orthopedic premaxillary retrution on craniofacial development in
      animal model].
AB  - OBJECTIVE: To observe the whole process of cranio-maxillofacial development of an
      animal model with bilateral premaxillary clefts, after being exerted with
      premaxillary retro-pressing forces. METHODS: Experimental rabbits with
      premaxillary clefts and without clefts were exerted with retro-pressing forces
      respectively. Roentgenographic cephalometric analysis and different
      investigations of premaxillary suture were performed during the whole
      craniofacial development. RESULTS: The longitudinal cephalometric analysis showed
      that a temporary retarding effect of mid-facial growth existed. The hindrance of
      maxillary growth potentiality did not occur in spite of being exerted retro
      pressing force as to this experimental extent. CONCLUSIONS: (1) Infant rabbit
      combined with the designed retro-pressing appliance is an ideal experimental
      model for quantitative study of active orthopedic treatment of protruding
      premaxilla. (2) Using active preoperative orthopedics to reposit the protruding
      premaxilla of bilateral cleft palate is a reasonable and effective approach.

PMID- 15454019
TI  - [Heterotopic chondrogenesis of human adipose tissue-derived stromal cells loading
      on alginate gel].
AB  - OBJECTIVE: To isolate and chondro-inductive culture of human adipose tissue
      derived stromal cells and to study their heterotopic chondrogenesis by loading
      them on alginate gel. METHODS: Liposuction human adipose tissues were minced and
      digested with collagenase type I. The obtained stromal cells were primarily
      cultured in BGJb medium for ten days. Secondary harvested cells were cultured in
      DMEM-F12 medium supplemented with 10%FBS, 6.25 mg/L insulin, 10 mg/L TGF-beta1,
      50 mg/L of freshly prepared L-ascorbate for 14 days. After in vitro assay of
      chondrogenic phenotypes, the cells at density of 10(10)/L were mixed with 1.2%
      alginate sodium and 102 mmol/L CaCl(2). The cross-linking cell-alginate gel were
      injected into four BALB/C athymic mice subcutaneously (1 ml for each mouse).
      Meanwhile, the auto-controls were set by injecting equal dose of simple alginate
      gel and pure cells in two opposite buttocks of the same mouse subcutaneously. Two
      mice were sacrificed at fourth and eighth week postoperatively and all samples
      were removed, fixed, embedded in paraffin and cut into sections of 5 micro m
      thick. HE staining, Alcian blue and modified Masson's trichrome staining were
      employed to observe chondrogenesis histologically. RESULTS: Alcian blue and
      immunocytochemical staining revealed chondroitin sulfate and collagen II in cell
      matrix after having been chondro-inductive cultured for 14 days. At intervals of
      fourth and eighth week, heterotopic chondrogenesis is (cartilage formed) within
      cell-alginate injected sites were found in all mice but negatively in auto
      controls. Histologically the hypertrophic chondrocytes were among cartilage
      matrix in different staining. All alginate gel and solitory cells absorbed within
      two to three weeks postoperatively in auto-controls. CONCLUSION: It seems that
      stromal cells derived from human adipose tissue presents a potential for
      chondrogenic differentiation.

PMID- 15454020
TI  - [Expression of cathepsin K and IL-6 mRNA in root-resorbing tissue during tooth
      movement in rats].
AB  - OBJECTIVE: To investigate the expression and the localization of Cathepsin K and
      IL-6 mRNA in root-resorbing tissue and to elucidate the molecular changes and
      mechanism of root resorption induced by tooth movement. METHODS: Rats were
      subject to experimental tooth movement to induce root resorption. In situ
      hybridization was performed to identify the cells in root-resorbing tissue that
      produced Cathepsin K or IL-6 the difference of CK mRNA or IL-6 mRNA expression
      between root resorption group and control group was calculated by t-test.
      RESULTS: Cathepsin K mRNA was highly and selectively expressed in multinuclear
      odontoclast and IL-6 mRNA expressed in fibroblast, osteoblast, osteocyte and
      cementoblast. The expression of Cathepsin K mRNA and IL-6 mRNA in root-resorbing
      tissue increased evidently compared with the normal periodontium. CONCLUSIONS:
      Odontoclast in the root-resorbing tissue expresses Cathepsin K mRNA that
      participates in proteolysis during root resorption. IL-6 plays a very important
      role in the root resorption as a multifunctional cytokine.

PMID- 15454021
TI  - [The changes of subgingival microbials during periodontal maintenance in patients
      with gingivitic and wearing fixed orthodontic appliances].
AB  - OBJECTIVE: To investigate the microbiological changes of subgingival microbials
      in patients with gingivitis and wearing fixed orthodontic appliances. METHODS: 48
      subjects (10 to 17 years old) with gingivitis, and wearing fixed orthodontic
      appliances, were divided randomly into three groups (placebo, NS and CH). Placebo
      group had normal saline mouthrinse; only and no oral hygiene instruction (OHI).
      The NS group had OHI and normal saline mouthrinse; The CH group had OHI and 0.12%
      chlorhexidine gluconate mouthrinse. Bacterial examinations were carried out on
      baseline, one week, one month and three months after scaling. The bacterial
      examination was carried out. The percentage of coccus, bacillus and spirochete
      was calculated. RESULTS: In placebo group and NS group, the percentage of coccus
      increased up to the third examination then dropped down. The spirochete's
      percentage changed inversely. CH group maintained an increasing trend in coccus'
      percentage and decreasing trend in spirochete's percentage. The percentage
      changes of coccus and bacillus between placebo group and CH group are
      statistically significant (P < 0.05). CONCLUSIONS: During the three-month
      examination, the CH group had better microbiologic change than the other two
      groups.

PMID- 15454022
TI  - [Maintain the persistent development status for private dental clinics].

PMID- 15454023
TI  - [Endodontics: special problems and management].

PMID- 15454024
TI  - [Candidates review guide on oral and maxillofacial surgery (1)].

PMID- 15454025
TI  - [Candidates review guide on oral and maxillofacial surgery (2)].

PMID- 15454026
TI  - [Candidates review guide on periodontology].

PMID- 15454027
TI  - [Influencing factors on distraction osteogenesis].

PMID- 15454028
TI  - [Advances research of periodontal disease and preterm low birth weight
      deliveries].

PMID- 15454029
TI  - [The application of functional magnetic resonance imaging on mastication
      research].

PMID- 15454034
TI  - [Rationally to diagnose and treat uveitis].

PMID- 15454035
TI  - [Increased expression of Fas and FasL mRNA in peripheral blood lymphocytes in
      Vogt-Koyanagi-Harada syndrome].
AB  - OBJECTIVE: To evaluate the expression of Fas and FasL messenger RNA (mRNA) in
      peripheral blood lymphocytes and its possible role in the pathogenesis of Vogt
      Koyanagi-Harada syndrome. METHODS: Blood samples were obtained from 16 patients
      with Vogt-Koyanagi-Harada syndrome and 19 healthy individuals from January to
      June, 2000. Total RNA was extracted from peripheral blood lymphocytes. cDNA was
      prepared from RNA with oligo d(T)(18) and M-MuLV reverse transcriptase. The
      expression of Fas mRNA and FasL mRNA in peripheral blood lymphocytes was
      determined using fluorescent quantitative polymerase chain reaction (FQ-PCR).
      Amplification was carried out through 32 cycles, 30 seconds denaturation at 93
      degrees C, 30 seconds annealing at 58 degrees C, and 45 seconds primer extension
      at 72 degrees C. The final extension time was 7 minutes. RESULTS: The expression
      of Fas mRNA on peripheral blood lymphocytes [(1.6 +/- 2.0) x 10(6)] was
      significantly higher than that of the controls [(5.7 +/- 2.0) x 10(5)] (t = 4.50,
      P < 0.05). The mRNA expression of FasL on peripheral blood lymphocytes [(1.8 +/-
      1.5) x 10(6)] was also higher than that of the controls [(4.8 +/- 3.5) x 10(5)]
      (t = 9.57, P < 0.05). CONCLUSIONS: A high level of Fas mRNA and FasL mRNA
      expression in activated peripheral blood lymphocytes is observed in patients with
      Vogt-Koyanagi-Harada syndrome. These long-persisted activated lymphocytes may be
      responsible for the perpetuation and recurrence of Vogt-Koyanagi-Harada syndrome.

PMID- 15454036
TI  - [Quantitative determination of aqueous flare and cells in the eyes of patients
      with inflammation of anterior uvea].
AB  - OBJECTIVE: To quantify aqueous flare and cells in the eyes of patients with
      inflammation of anterior uvea by FC-2000 laser flare cell meter (LFCM), and to
      compare these results with those obtained with slit lamp microscopy. METHODS:
      Aqueous flare and cells of 194 eyes of 110 patients with inflammation of anterior
      uvea and 52 eyes of 52 healthy subjects were graded into 0, 1+, 2+, 3+ and 4 +
      scale based on a previously described system using slit lamp microscopy. LFCM was
      also used for evaluation of aqueous flare and cells. RESULTS: All eyes in normal
      individuals were graded as "0" scale of both flare and cells by silt lamp
      microscopy. Flare of grade 0, 1+ and 2+ were noted in 74, 98 and 18 eyes, and
      cell of grade 0, 1+, 2+, 3+ and 4+ were noted in 124, 26, 19, 14 and 11 eyes in
      uveitis patients, respectively. LFCM examination revealed that the mean flare
      values in uveitis eyes with flare of grade 0, 1+ and 2+ were 7.9, 29.5 and 189.0
      photon count/ms, respectively. In patients with flare of grade 3+ and 4+, LFCM
      readings were unreliable because of increased background noise. There was
      significant correlation between slit lamp examination and the laser flare
      measurement for flare of grade 0, 1+ and 2+ (r = 0.75, P < 0.001). The mean flare
      values were significantly higher in patients with flare of grade 0, 1+ and 2+
      than that in normal controls (5.3 pc/ms) (t = 5.872, P < 0.05). The mean cell
      numbers in the eyes with cell of grade 0, 1+, 2+, 3+ and 4+ were 1.5, 12.1, 33.9,
      84.9 and 193.1 count/0.5 mm(3), respectively. The results of slit lamp
      examination showed significant correlation with laser cell counts measurement (r
      = 0.72, P < 0.001). The mean cell numbers were significantly higher in uveitis
      patients than that in normal controls (0.9 count/0.5 mm(3)) (t = 7.351, P <
      0.05). CONCLUSIONS: Our results indicate that LFCM is able to evaluate precisely
      the mild and moderate breakdown of blood aqueous barrier and inflammation of the
      anterior uvea tract, therefore it provides an important parameter for the
      treatment of anterior uveitis.

PMID- 15454037
TI  - [Long-term effect of combined penetrating keratoplasty and pars plana vitrectomy
      with temporary keratoprosthesis].
AB  - OBJECTIVE: To evaluate the long-term effect of combined penetrating keratoplasty,
      pars plana vitrectomy and temporary keratoprosthesis for the treatment of
      complicated anterior and posterior segment diseases. METHODS: Combined
      penetrating keratoplasty and pars plana vitrectomy were performed in 107 eyes
      with temporary keratoprosthesis. The mean follow-up period was 13 months. Visual
      acuity, graft transparency, intraocular pressure and vitreoretinal anatomic
      status were examined during the follow-up. The criteria of success of the
      operation included a transparent graft, reattached retina and normal intraocular
      pressure with or without medication. RESULTS: Ninety-two eyes. 86.0%) could be
      preserved after the operation, including 78 eyes (72.9%) with clear graft,
      reattached retina and normal intraocular pressure. Graft rejection occurred in 34
      eyes (31.8%), atrophy of the eye in 13 eyes (12.2%) and secondary glaucoma in 15
      eyes (14.0%). The success rate for re-attachment of the retina was higher in eyes
      without pre-operative proliferative vitreoretinopathy. CONCLUSIONS: Combined
      penetrating keratoplasty and pars plana vitrectomy with temporary
      keratoprosthesis appear to be effective in the treatment of severe ocular injury.
      Decompensation of corneal endothelium function and proliferative
      vitreoretinopathy are the main causes for failure of the operation.

PMID- 15454038
TI  - [Reconstruction of rabbit corneal stroma using tissue engineering technique].
AB  - OBJECTIVE: Reconstruct corneal stroma by tissue engineering. METHODS: Primary
      corneal stromal cells were isolated from newborn rabbit cornea. When the cultured
      cells reaching confluence, the stromal cells were mixed with polyglycolic acid
      (PGA) to form a cell-scaffold construct. After 1 week in vitro culture, the
      constructs were implanted into mother rabbit corneal stroma. Parts of corneal
      stromal cells were transfected with GFP gene as mark of transplanted cells.
      Tissues were harvested at 8 weeks for transmission electron microscopy (TEM),
      histology and Western blot evaluation. In control, PGA alone was implanted into
      the other cornea. RESULTS: The engineered corneal stroma became transparent
      gradually over a period of 8 weeks. The histology of engineered stromal lamellar
      was relatively similar to that of natural one, no significant differences were
      found in the diameter of cornea collagen fiber [(29.4 +/- 4.7) nm] in
      experimental rabbits compared with control [(28.5 +/- 3.5) nm], Student's t-test:
      P = 0.1316 > 0.05. TEM demonstrated that collagen fibrils deposited in engineered
      stroma had a similar diameter compared to that of normal counterpart. In
      addition, Western blot showed the positive expression of type I collagen in the
      collagen fibrils. In contrast, no new stroma tissue was formed when PGA alone
      implanted. A green colored stroma was observed when engineered with GFP-labeled
      cells under fluorescence light microscope. CONCLUSION: The results demonstrate
      that nearly transparent corneal stroma can be obtained by the technique of cornea
      engineering.

PMID- 15454039
TI  - [Expression of vascular endothelial growth factor and its receptor in
      experimental choroidal neovascularization in rat].
AB  - OBJECTIVE: To study the expressions of vascular endothelial growth factor and its
      receptor FLK1 in krypton laser-induced choroidal neovascularization (CNV) in
      Brown Norway rat. METHODS: Thirty anesthetized male Brown Norway rats received
      krypton laser (647 nm, 360 mW, 50 micro m, 0.05 s) to induce CNV. Fundus
      fluorescein angiography examinations were performed just before euthanasia on
      days 3, 7, 14, 21, 28 and 56 after laser photocoagulation. The retina was
      processed for histopathology analysis. VEGF mRNA, VEGF and FLK1 expressions were
      demonstrated using in situ hybridization and immunohistochemistry staining
      respectively. RESULTS: VEGF mRNA expression was mainly observed in the vascular
      endothelial cells, the ganglion cells, the inner nuclear layers, the retinal
      pigment epithelial cells in normal retina and the vascular endothelial cells of
      normal choroid of BN rat. VEGF mRNA expressed in the vascular endothelial cells,
      the ganglion cells, the inner nuclear layers, lesion of outer nuclear layers in
      retina on days 3 after photocoagulation, but CNV wasn't detected. The level of
      VEGF mRNA expression in retina was decreased after 3 days (P < 0.01). CNV was
      firstly observed on day 7 after photocoagulation by FFA and histopathology. The
      area and density of positively stained cells for VEGF mRNA in CNV were increased
      during the development of CNV (P < 0.01) and no significant change after days 21
      (P > 0.05). FLK1 was detected in the vascular endothelial cells, the ganglion
      cells of normal retina and the vascular endothelial cells of choroid. The
      staining of FLK1 was positive in laser induced CNV after days 7, the level of the
      receptor expression was increased during the development of CNV (P < 0.01) and
      was not significantly changed after days 21 (P > 0.05). CONCLUSIONS: VEGF and its
      receptor FLK1 accumulation and combination in the lesion of retina and choroid
      are related to choroidal neovascularization induced by laser.

PMID- 15454040
TI  - [Inhibiting proliferation of cultured rat lens epithelial cells by bFGF antisense
      oligonucleotides and their liposomes].
AB  - OBJECTIVE: To evaluate the effects of basic fibroblast growth factor (bFGF)
      antisense oligonucleotides and their liposomes on the proliferation of cultured
      rat lens epithelial cells (LECs). METHODS: The rat LECs were cultured and bFGF
      antisense oligonucleotides (AONs), sense oligonucleotides (SONs), AON liposomes,
      SON liposomes were added to second passage of cells supplied with DMEM while
      empty liposomes served as controls. MTT assay was used to examine the
      proliferation of LECs, and RT-PCR was performed to quantify bFGF mRNA expression
      in LECs 24 h after treatment. RESULTS: The Shapes of rat LECs were polygonal
      after 24 h in culture. Cell confluence was reached in 2 - 3 weeks. After
      subculture, confluence was occurred in 1 - 2 weeks. The results of MTT assay were
      showed that the absorption (A) value of bFGF AONs was 0.138 +/- 0.074, and that
      of bFGF SONs and DMEM control were 0.325 +/- 0.097 and 0.370 +/- 0.079,
      respectively. The A value of AONs was significantly less than SONs and DMEM alone
      (P = 0.024, P = 0.005). The absorption (A) value of bFGF AON liposomes was 0.128
      +/- 0.032, and that of bFGF SON liposomes and liposomes alone were 0.238 +/-
      0.120 and 0.348 +/- 0.017. The absorption (A) value of AON liposomes was not
      significantly different from that of liposomes negative control (P = 0.000). By
      RT-PCR, the amounts of PCR product for bFGF AONs, SONs and DMEM control were 0.33
      micro g, 0.99 micro g, 0.85 micro g. The amounts of PCR product of bFGF AON
      liposomes, SON liposomes and liposomes only were 0.23 micro g, 0.48 micro g, 0.56
      micro g. CONCLUSIONS: The proliferation of cultured rat LECs is inhibited by the
      treatment of the antisense oligonucleotides, the inhibition is correlated with
      decreased expression of bFGF mRNA.

PMID- 15454041
TI  - [Organ culture for preservation of the cornea: human umbilical cord serum versus
      fetal bovine serum].
AB  - OBJECTIVE: To evaluate the changes of porcine corneal endothelium, the
      morphology, histology, ultrastructure, enzymes activity and metabolism of the
      cornea induced by organ culture with two different media containing fetal bovine
      serum (FBS) or human umbilical cord serum (HCS). METHODS: Fifty pairs of porcine
      corneas were preserved at 31 degrees C for 7, 14, 21, 28 days. One cornea of each
      pair was cultivated in medium I containing 10% FBS (group 1); the other one was
      stored in medium II containing 10% HCS (group 2). Thirteen fresh porcine corneas
      served as controls. All stored corneas were dehydrated for 24 hours. Twelve
      corneas from each group were evaluated each week, including the morphology,
      histology and enzyme histochemical staining of the cornea. Scanning electron
      microscopy was performed on one cornea from each group at 14 and 28 days and
      compared with the fresh cornea. pH value, glucose and lactate concentration of
      the culture media before and after culture were examined. Microbiological
      evaluation was also performed. RESULTS: Endothelium evaluation did not differ
      statistically between the two groups of porcine corneas. The morphological
      endothelium study showed some alterations such as pleomorphism. After 28 days of
      cultivation, the mean cell losses of endothelium were 10.98% and 10.85% in medium
      I and medium II stored corneas, respectively. There were no statistical
      differences of the histology, ultrastructure and enzymes activity of corneas
      between the two groups. The histological study showed corneal swelling and
      epithelial sloughing after preservation. Scanning electron microscopy showed an
      intact endothelial layer in all corneas. Enzyme histochemical staining showed
      vigorous enzyme activity in the corneal epithelium and endothelium. Enzyme
      activity in stroma decreased with preservation time. Corneas showed good glucose
      metabolism. Incidence of contamination was 6% for storage medium. CONCLUSIONS:
      The corneal endothelium can maintain a good viability for 4 weeks in these two
      organ culture media. HCS can replace FBS in the organ culture medium.

PMID- 15454042
TI  - [Receptor mediated endocytosis of retinal pigment epithelial cell].
AB  - OBJECTIVE: To evaluate the possibility and mechanism of the turnover of the
      negatively charged macromolecule by retinal pigment epithelial (RPE) cells.
      METHODS: Cultured porcine RPE eye cups were incubated with fluorescence labeled
      formaldehyde treated serum albumin (F-FSA), a classical ligand for scavenger
      receptors. The endocytosis of F-FSA by RPE cells under different conditions was
      evaluated systematically by fluorescent microscopy and electron microscopy.
      RESULTS: The amount of F-FSA ingested by RPE cells depends on the incubation time
      and the concentration of ligand. Similar ligands compete for the binding site of
      RPE cells. Small vesicles containing F-FSA are noticed in the cytosol of RPE
      cells as demonstrated by electron microscopy. CONCLUSION: The RPE cells can
      effectively ingest negatively charged macromolecules, possibly by scavenger
      receptor mediated endocytosis.

PMID- 15454043
TI  - [Effect of cytokine and sandostatin on collagen synthesis and expression of
      procollagen mRNA by lens epithelial cells].
AB  - OBJECTIVE: To study the effects of epidermal growth factor (EGF), interleukin-1
      (IL-1), interferon-gamma (IFN-gamma) and sandostatin on collagen synthesis and
      expression of types I and III procollagen mRNA by bovine lens epithelial cells in
      vitro. METHODS: Cells were plated in 96-well tissue culture plates. After
      attached, serum-free medium containing EGF 10(-2) - 10(2) ng/ml, IL-1 10 - 10(5)
      ng/ml, sandostatin 10(-11) - 10(-7) mol/L and IFN-gamma 10 - 10(5) U/ml were
      added into the plates. Collagen synthesis was measured with (3)H-proline
      incorperation, and expression of procollagen mRNA was detected with Northern
      blot. RESULTS: EGF 10(-1) - 10(2) ng/ml and IL-1 10(2) - 10(5) ng/ml obviously
      promoted collagen synthesis. EGF 1 ng/ml and IL-1 10(3) ng/ml increased the
      expression of types I and III procollagen mRNA. IFN-gamma 10(3) - 10(5) ng/ml and
      sandostatin 10(-10) - 10(-7) mol/L decreased collagen synthesis. IFN-gamma 10(3)
      U/ml and sandostatin 10(-9) mol/L decreased the expression of types I and III
      procollagen mRNA. CONCLUSIONS: EGF and IL-1 may enhance the occurrence of
      posterior capsular opacification, they affect types I and III procollagen gene
      expression at transcription level. IFN-gamma and sandostatin might be used to
      prevent the occurrence of posterior capsular opacification.

PMID- 15454044
TI  - [Comparison of microinjection methods for subretinal RPE transplantation in the
      rat].
AB  - OBJECTIVE: To compare iatrogenic damage to the host eye caused by different
      injection techniques for transplantation RPE into the subretinal space of Lewis
      rats. METHODS: A total of 45 eyes from Lewis rats were divided into three groups
      and immortalized hTERT-RPE1 cells (clontechniques) transfected with green
      fluorescent protein (GFP) was injected into the subretinal space. The injection
      was given by using Hamilton syringe, Eppendorf repeat micro-pipettor, or a
      pediatric syringe infusion pump in different groups respectively. Iatrogenic
      damage to the host eye was evaluated by light microscopy. RESULTS: No damage to
      the host eye was observed in 12 of 15 eyes injected with the syringe infusion
      pump. In contrast, severe or mild damage was detected in 14 of 15 eyes after
      injections using either the Hamilton syringe or the Eppendorf micro-pipettor.
      CONCLUSIONS: The syringe infusion pump minimizes iatrogenic damage to the host
      eye during RPE transplantation into the subretinal space of the rat. The slow and
      controlled fluid infusion provided by the low-geared electric motor of the pump
      is presumably beneficial during the surgical procedure.

PMID- 15454045
TI  - [Subretinal transplantation of genetically modified human retinal pigment
      epithelium cells delay photoreceptor degeneration and functional deterioration in
      rats].
AB  - OBJECTIVE: To investigate whether subretinal transplantation of genetically
      modified human retinal pigment epithelium cells can rescue photoreceptor
      degeneration in RCS rats. METHODS: A spontaneously derived adult human retinal
      pigment epithelium (RPE) cell line (CRL-2302) was infected by gfp retrovirus,
      then transfected by liposome mediated CNTF expression plasmid transfer. Around 1
      x 10(5) genetic modified cells were injected to subretinal space of the right eye
      at 4 - 5 weeks old, the left eye was left without injection or injected with PBS
      as controls. RESULTS: The GFP expression cells under the retina were observed
      from 1 to 6 weeks after transplantation. Histologic and ultrastructural
      assessment demonstrated substantial sparing of photoreceptors and correction of
      RPE phagocytosis defect. Electrophysiological assessment revealed an increased
      sensitivity of treated eyes to white light. CONCLUSION: The results demonstrate
      that potential of genetically modified RPE cells for ultimate application in
      therapeutic transplantation strategies for human retinal degenerative diseases.

PMID- 15454054
TI  - [Recovery of vision acuity is critical following macular surgery].

PMID- 15454055
TI  - [To be circumspect about undertaking extensive retinomomy or retinectomy].

PMID- 15454056
TI  - [Influence of membrane dissection and en bloc excision on the outcome of vitreous
      surgery in proliferative diabetic retinopathy].
AB  - OBJECTIVE: Compare membrane dissections and en bloc membranectomy in vitrectomy
      of proliferative diabetic retinopathy. METHODS: Retrospective comparative (non
      randomized) interventional study. 296 eyes of 276 patients with fibrovascular
      proliferation in diabetic retinopathy performed by vitrectomy from 1996
      approximately 2000 were analyzed. 201 eyes complicated with vitreous hemorrhages
      in different severity, 110 eye with traction retinal detachment. We used membrane
      dissection in 110 eyes and en bloc excision in 186 eyes. Follow up time required
      more than 4 months, for the silicone oil temponade eyes required 3 months after
      silicone oil removal. The iatrogenic holes, postoperative hemorrhages, rubeosis
      iridis and visual improvement were compared in the same intraocular temponade for
      membrane dissections and en bloc excision, as well as visual acuity > 0.1.
      RESULTS: There is no statistic significant difference in age, sex and type of
      fibrovascular proliferations for both groups. Membrane dissection techniques
      showed a lower incidence of iatrogenic breaks (35.5%) than that in en bloc
      membranectomy techniques, no significant difference in postoperative vitreous
      hemorrhages and visual improvement for both techniques. CONCLUSION: Both
      techniques showed no difference to visual results and postoperative
      complications, but membrane dissection techniques can decrease the formation of
      iatrogenic breaks.

PMID- 15454057
TI  - [The recovery of the visual function and morphological closure of the idiopathic
      macular hole after vitrectomy].
AB  - OBJECTIVE: To investigate the relation of the visual function recovery and the
      postoperative form of the idiopathic macular holes. METHODS: 38 eyes with macular
      holes which were closed after one surgery were selected and were grouped into
      type of complete healed, partial healed and no healed by Optical Coherent
      Tomography (OCT). Scanning Laser Ophthalmoscope (SLO) examination were performed
      preoperatively and 1 month, 3 months and 6 months postoperatively to detect the
      sensitivity, areas of absolute scotoma, relative scotoma and central visual
      acuity. RESULTS: Among type of complete healed group and type of partial healed
      group 6 months after vitrectomy the central vision, sensitivity, areas of
      absolute scotoma and relative scotoma had statistical significant improvement.
      The central vision and sensitivity improved postoperatively and areas of absolute
      scotoma and relative scotoma had no significant changes in type of no healed
      group. The extent of improvement of vision, sensitivity, absolute scotoma in type
      of complete healed group was more greater than type of partial healed group and
      no healed group. The fovea configuration of stage II macular holes was easier to
      recover completely. CONCLUSIONS: The recovery of the normal curvature of macular
      fovea is positive to the improvement of the visual function. The better the fovea
      contour recover, the more significantly the visual function improve. The early
      stage of macular holes (stage II) could get better improvement of visual
      function.

PMID- 15454058
TI  - [Differentiation of human embryonic retinal cells in vitro].
AB  - OBJECTIVE: To study the conditions to induce differentiation of human embryonic
      retinal cells (HRCs) in vitro. METHODS: HRCs were isolated from neural retinas of
      16th-20th week of gestation embryo and cultured in serum-free media. Retinal cell
      differentiation was induced by serum-containing media and by the mouse retinal
      pigment epithelium (RPE) eye cup whick mimic the retinal environment in vivo. The
      expression of Nestin and several differentiated retinal cell markers was
      investigated by immunostaining. Real time RT-PCR analysis was used to evaluate
      the mRNA level of nestin gene in HRCs and differentiated retinal cells. RESULTS:
      HRCs cultured in serum-containing medium can differentiate into glial cell (GFAP
      positive), ganglion cell (Thy1 positive) and bipolar cell (PKCalpha positive).
      HRCs cultured in mouse RPE eye cup can also express photoreceptor marker
      rhodopsin and amacrine marker syntaxin. Nestin downregulate significantly in
      differentiated HRCs. CONCLUSION: RPE appeares to play an important role in the
      differentiation of retinal photoreceptors and amacrine cells in vitro.

PMID- 15454059
TI  - [In vitro experimental study of the effects of different introcular irrigating
      solutions on the viability of rat retinal neuron cells].
AB  - OBJECTIVE: To observe the effects of different introcular irrigating solutions on
      the viability of retinal neuron cells, their antioxidant ability, and to find the
      ideal introcular irrigating solution. METHODS: Retinal neuron cells from Sprague
      Dawley rats (postnatal 1 - 3 days) were cultured in the 4 different introcular
      irrigating solutions which were BSS plus, BSS plus + drugs (tobramycin1.6 ten
      thousand unit/L, desamethasone 16 mg/L and adnephrin 1 mg/L), new irrigating
      solution and lactated Ringer's solution + drugs. Cell viability was determinated
      by MTT [3,(4,5-Dimethylthiazol-2-yl)2,5-diphenyl-tetrazolium bromide] assay, LDH
      release was tested by LDH assay and apoptotic cell death was evaluated by the
      TUNEL (TdT-mediated dUTP nick-end labeling) assay after retinal neuron cells were
      cultured in the different introcular irrigating solutions for 4, 12, 24, 48
      hours. MDA (malondialdehyde) production was tested after the cells exposed to 30
      micro mol/L H(2)O(2) for 4 hours. All data was analyzed in Dunnett's ANOVA way.
      RESULTS: The cell viability was decreased and the rate of LDH released and cell
      apoptosis was increased. These effects were shown to be time-dependent for the
      same solution. At the same time point, the effects on cellular survive was
      variable in deferent introcular irrigating solutions, BSS plus is the lowest, BSS
      plus + drugs and modified irrigating solution are midst, and lactated Ringer's
      solution + drugs is the highest. The result of MDA assay showed that both BSS
      plus and modified irrigating solution can inhibit the oxidative damage induced by
      H(2)O(2). CONCLUSION: Modified introcular irrigating solution may be an better
      introcular irrigating solution according to its little effect on cell viability,
      its antioxidant function and lower cost.

PMID- 15454060
TI  - [An experimental study on dissolving and detaching vitreoretinal interface with
      enzymes].
AB  - OBJECTIVE: To investigate the safety dosage of intravitreal injection of Plasmin,
      Hyaluronidase and their combination and to evaluate their efficacy in the
      formation of posterior vitreous detachment (PVD) through animal experiments.
      METHODS: Eight rabbits each were randomly assigned to one of six groups and one
      eye of each rabbit were experimental eye, the other is control eye. The position
      of drug injection was in posterior 1/3 of vitreous before papillary. The drug
      injection groups were assigned as following: the first group-Hyaluronidase 20 IU
      (0.1 ml BSS), the second group-Hyaluronidase 30 IU (0.1 ml BSS), the third group
      Plasmin 1 IU (0.1 ml BSS), the forth group-Plasmin 2 IU (0.1 ml BSS), the fifth
      group-Plasmin 3 IU (0.1 ml BSS), the sixth group- Hyaluronidase 20 IU (0.05 ml
      BSS) combined with Plasmin 1 IU (0.05 ml BSS); the control eyes were injected
      with BSS (0.1 ml) at the same position. The experimental rabbits were followed
      for 2 weeks, and in this period all eyes were examined with slit-lamp
      biomicroscopy, +90 D preset lens, indirect ophthalmoscope, electroretinography, B
      scan, and optical coherence tomography. After two weeks, the animals were killed
      and the eyes enucleated. Scan electron and light microscopy were performed.
      RESULTS: Hyaluronidase concentration of 20 IU, Plasmin concentration of 1 IU and
      their combination didn't produce inflammatory response and retinal toxicity in
      the experimental eyes. 30 IU Hyaluronidase and 2 IU Plasmin both caused mild
      inflammatory response in the vitreous without retinal histological changes, while
      the latter caused a reversible decrease in the ERG b-wave. 3 IU of Plasmin caused
      severe inflammatory response with retinal histological and electroretinographic
      changes. In safety dosage neither Hyaluronidase nor Plasmin alone were successful
      in producing completely posterior vitreous detachment (PVD), but the latter can
      produce partial PVD. The combination of Plasmin (1 IU) and Hyaluronidase (20 IU)
      was effective on producing completely PVD without retinal toxicity. CONCLUSION:
      20 IU of Hyaluronidase and 1 IU of Plasmin are safe to retina and others
      structures in the eyes without any toxicity. Posterior vitreous injection of
      Hyaluronidase (20 IU) combined with Plasmin (1 IU) can produce complete posterior
      vitreous detachment.

PMID- 15454061
TI  - [Morphologic characteristics of cornea in Fuchs endothelial dystrophy observed by
      confocal microscopy].
AB  - OBJECTIVE: To analyze the image of corneas with Fuchs endothelial dystrophy using
      confocal microscopy in vivo. METHODS: Central corneas of 38 eyes (19 patients
      aged 33 approximately 76 years) were examined using scanning slit confocal
      microscopy in vivo after being diagnosed with Fuchs endothelial dystrophy. They
      were divided into two groups namely symptomatic (19 eyes) and asymptomatic (19
      eyes). The control group comprised of 30 normal eyes. The images were analyzed
      visually for morphology of corneas and the densities of cells, as well as the
      diameter of the guttae and the corneal nerves were counted by NAVIS software.
      RESULTS: (1) In the symptomatic groups, confocal microscopy revealed guttae in 19
      eyes. The diameter of the guttae ranged from 20 to 60 micro m. The density of
      endothelial cells was statistically significant compared with the control group
      (t = 18.74, P < 0.01). Descemet's membrane was thickened in 9 eyes. Dark bands
      6.0 approximately 10.8 micro m in diameter were detected in 14 eyes. All eyes
      showed a diffuse increased light reflection in the stroma.17 eyes exhibited an
      abnormal Bowman's layer: multiple focal bright reflection. 10 eyes revealed
      normal corneal nerves. The differences between posterior and anterior keratocyte
      densities in the control and study groups were not statistically significantly
      different (t = 0.854, 1.173; P = 0.38, 0.24 respectively). (2) In the
      asymptomatic groups, less number of guttae could be seen in the endothelial
      layer. The diameter of the guttae was 15 approximately 40 micro m. The densities
      of endothelial cells were not significantly different compared with control group
      (t = 1.998, P = 0.053). Other layers of the cornea exhibited no other abnormal
      phenomenon. The densities of endothelial cells between symptomatic and
      asymptomatic groups were statistically significantly different (t = 8.352, P <
      0.01). CONCLUSIONS: Morphologic characteristics of cornea are observed by
      confocal microscopy in Chinese patients with Fuchs endothelial dystrophy.
      Preliminary results demonstrate that there is no significant difference between
      Chinese and western patients. Confocal microscopy allows to diagnose Fuchs
      dystrophy and visualize endothelial cells within the swollen cornea. And it is
      especially useful for patients whose endothelial cells can not be seen with non
      contact specular microscopy.

PMID- 15454062
TI  - [Effects after orthokeratology on corneal topography and monochromic wavefront
      aberration].
AB  - OBJECTIVE: To assess the corneal topography and monochromatic wavefront
      aberration among subjects using orthokeratology. Changes of ocular optical
      quality and related visual functions induced by corneal topography were studied.
      METHODS: Twenty-five young myopic subjects (50 eyes) were recruited with myopia
      from -1.75 approximately -4.75 D. Orthokeratology lens were fitted at the initial
      visit with overnight wear program. Subjective refraction, corrective visual
      acuity, corneal topography and slit lamp examination were performed before and 1
      day, 1 week, 2 weeks, 4 weeks, 8 weeks and 12 weeks after the fitting of
      orthokeratology lens. The monochromic wavefront aberration was measured in
      initial visit and after 12 weeks. RESULT: The best corrected visual acuity was
      reduced significantly from (-0.0628 +/- 0.0286) LogMAR (before orthokeratology)
      to -0.0120 +/- 0.0318 (12 weeks after orthokeratology) (F = 17.821, P < 0.001).
      Root-mean-square (RMS) of wavefront aberration increased significantly from
      (0.5766 +/- 0.4771) micro m (before orthokeratology) to (1.3731 +/- 0.8039) micro
      m (12 weeks after orthokeratology) (F = 36.513, P < 0.001). RMS of Zernike
      function of each order was increased as well. The rate of eccentric in posterior
      surface of corneal increased significantly after the using of orthokeratology
      lens. CONCLUSIONS: Orthokeratology is one of the effective methods for reducing
      myopia temporarily. However, the best corrected visual acuity is decreased after
      using of orthokeratology. The increase of aberration induced by orthokeratology
      can be the cause of reduction of ocular optical quality.

PMID- 15454063
TI  - [Effect of phacoemulsification versus extracapsular extraction on visual acuity:
      a meta-analysis].
AB  - OBJECTIVE: To examine the efficacy of phacoemulsification (Phaco) versus
      extracapsular extraction (ECCE) on visual acuity. METHODS: 9 cases related with
      Phaco and ECCE were retrieved from PubMED and Chinese biomedical data base. The
      combinability of the studies was assessed in terms of clinical and statistical
      criteria. Treatment effect was measured as risk difference between
      phacoemulsification and extracapsular extraction. Pooled estimates were analyzed
      with computer according to a random-effects model. RESULTS: A total of 1192
      patients were included in 9 trials. The pooled risk differences of visual acuity
      0.5 or better after surgery one week or 3 month were 24% (95% CI is 10% - 37%),
      20% (95% CI is 14% - 25%) respectively. The complications extracapsular
      extraction rates (36.8%) of phacoemulsification was lower than extracapsular
      extraction (62.1%). CONCLUSIONS: Phacoemulsification is a safer and reliable
      surgery for restoration of visual acuity in patients with cataract, and is
      superior to extracapsular cataract extraction.

PMID- 15454064
TI  - [High expression of catalase inhibiting of activated oxygen-induced apoptosis of
      len epithelial cell apoptosis].

PMID- 15454065
TI  - [Application evaluation of endoscopic surgery in proliferative diabetic
      retinopathy ].

PMID- 15454066
TI  - [Study on the establishment of image information network in ophthalmology ].

PMID- 15454067
TI  - [Acute pancreatitis complicated with retino-choroidal disease--long-term follow
      up study of a case].

PMID- 15454068
TI  - [Phacoemulsification complicated with suprachoroidal hemorrhage--report of 5
      cases].

PMID- 15454069
TI  - [Long-term polymethylmethacrylate contact lens wear--a case report].

PMID- 15454070
TI  - [Bilateral orbital varicose vein complicated with right eyelid hemorrhage. a case
      report].

PMID- 15454071
TI  - [The pathogenesis of retinal ganglia cell apoptosis induced by glaucoma].

PMID- 15454072
TI  - [Diagnosis and treatment of allergic conjunctivitis].

PMID- 15454073
TI  - Francis Crick (1916-2004).

PMID- 15454074
TI  - The power of pumping together; deconstructing the engine of a DNA replication
      machine.
AB  - The replicative DNA helicase lies at the heart of the eukaryotic replication
      machine, yet how it works remains puzzling. New structures of the viral
      replicative helicase SV40 T antigen suggest that a novel concerted mode of
      nucleotide binding and hydrolysis powers conformation changes and DNA unwinding.

PMID- 15454075
TI  - Neuronal differentiation: TOR and insulin receptor pathways set the tempo.
AB  - Target of rapamycin (TOR) and insulin receptor pathways regulate growth in
      metazoans. A recent study reveals a novel role for these pathways in controlling
      the timing of neuronal differentiation during Drosophila development, thus
      allowing a tight coordination between growth and differentiation programs.

PMID- 15454076
TI  - PGC-1alpha: turbocharging mitochondria.
AB  - PGC-1alpha plays essential and diverse functions in the control of metabolism
      ranging from mitochondrial biogenesis and respiration to hepatic gluconeogenesis
      and muscle fiber-type switching. In a paper in this issue of Cell, the
      characterization of PGC-1alpha(-/-) mice illustrates these pleiotropic functions
      and reveals an unexpected role for PGC-1alpha in the brain.

PMID- 15454078
TI  - Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including
      arrhythmia and autism.
AB  - Ca(V)1.2, the cardiac L-type calcium channel, is important for excitation and
      contraction of the heart. Its role in other tissues is unclear. Here we present
      Timothy syndrome, a novel disorder characterized by multiorgan dysfunction
      including lethal arrhythmias, webbing of fingers and toes, congenital heart
      disease, immune deficiency, intermittent hypoglycemia, cognitive abnormalities,
      and autism. In every case, Timothy syndrome results from the identical, de novo
      Ca(V)1.2 missense mutation G406R. Ca(V)1.2 is expressed in all affected tissues.
      Functional expression reveals that G406R produces maintained inward Ca(2+)
      currents by causing nearly complete loss of voltage-dependent channel
      inactivation. This likely induces intracellular Ca(2+) overload in multiple cell
      types. In the heart, prolonged Ca(2+) current delays cardiomyocyte repolarization
      and increases risk of arrhythmia, the ultimate cause of death in this disorder.
      These discoveries establish the importance of Ca(V)1.2 in human physiology and
      development and implicate Ca(2+) signaling in autism.

PMID- 15454077
TI  - Sculpting the proteome with AAA(+) proteases and disassembly machines.
AB  - Machines of protein destruction-including energy-dependent proteases and
      disassembly chaperones of the AAA(+) ATPase family-function in all kingdoms of
      life to sculpt the cellular proteome, ensuring that unnecessary and dangerous
      proteins are eliminated and biological responses to environmental change are
      rapidly and properly regulated. Exciting progress has been made in understanding
      how AAA(+) machines recognize specific proteins as targets and then carry out ATP
      dependent dismantling of the tertiary and/or quaternary structure of these
      molecules during the processes of protein degradation and the disassembly of
      macromolecular complexes.

PMID- 15454079
TI  - Architecture of the hin synaptic complex during recombination: the recombinase
      subunits translocate with the DNA strands.
AB  - Most site-specific recombinases can be grouped into two mechanistically distinct
      families. Whereas tyrosine recombinases exchange DNA strands through a Holliday
      intermediate, serine recombinases such as Hin generate double-strand breaks in
      each recombining partner. Here, site-directed protein crosslinking is used to
      elucidate the configuration of protein subunits and DNA within the Hin synaptic
      complex and to follow the movement of protein subunits during DNA strand
      exchange. Our results show that the protein interface mediating synapsis is
      localized to a region within the catalytic domains, thereby positioning the DNA
      strands on the outside of the Hin tetrameric complex. Unexpected crosslinks
      between residues within the dimerization helices provide evidence for a
      conformational change that accompanies DNA cleavage. We demonstrate that the Hin
      subunits, which are linked to the cleaved DNA ends by serine-phosphodiester
      bonds, translocate between synapsed dimers to exchange the DNA strands.

PMID- 15454080
TI  - Mechanisms of conformational change for a replicative hexameric helicase of SV40
      large tumor antigen.
AB  - The large tumor antigen (LTag) of simian virus 40, an AAA(+) protein, is a
      hexameric helicase essential for viral DNA replication in eukaryotic cells. LTag
      functions as an efficient molecular machine powered by ATP binding and hydrolysis
      for origin DNA melting and replication fork unwinding. To understand how ATP
      binding and hydrolysis are coupled to conformational changes, we have determined
      high-resolution structures ( approximately 1.9 A) of LTag hexamers in distinct
      nucleotide binding states. The structural differences of LTag in various
      nucleotide states detail the molecular mechanisms of conformational changes
      triggered by ATP binding/hydrolysis and reveal a potential mechanism of concerted
      nucleotide binding and hydrolysis. During these conformational changes, the
      angles and orientations between domains of a monomer alter, creating an "iris"
      like motion in the hexamer. Additionally, six unique beta hairpins on the channel
      surface move longitudinally along the central channel, possibly serving as a
      motor for pulling DNA into the LTag double hexamer for unwinding.

PMID- 15454081
TI  - The CREB coactivator TORC2 functions as a calcium- and cAMP-sensitive coincidence
      detector.
AB  - Elevations in circulating glucose and gut hormones during feeding promote
      pancreatic islet cell viability in part via the calcium- and cAMP-dependent
      activation of the transcription factor CREB. Here, we describe a signaling module
      that mediates the synergistic effects of these pathways on cellular gene
      expression by stimulating the dephosphorylation and nuclear entry of TORC2, a
      CREB coactivator. This module consists of the calcium-regulated phosphatase
      calcineurin and the Ser/Thr kinase SIK2, both of which associate with TORC2.
      Under resting conditions, TORC2 is sequestered in the cytoplasm via a
      phosphorylation-dependent interaction with 14-3-3 proteins. Triggering of the
      calcium and cAMP second messenger pathways by glucose and gut hormones disrupts
      TORC2:14-3-3 complexes via complementary effects on TORC2 dephosphorylation;
      calcium influx increases calcineurin activity, whereas cAMP inhibits SIK2 kinase
      activity. Our results illustrate how a phosphatase/kinase module connects two
      signaling pathways in response to nutrient and hormonal cues.

PMID- 15454082
TI  - MTA3 and the Mi-2/NuRD complex regulate cell fate during B lymphocyte
      differentiation.
AB  - The transcriptional repressor BCL-6 regulates B lymphocyte cell fate during the
      germinal center reaction by preventing terminal differentiation of B lymphocytes
      into plasma cells until appropriate signals are received. Here, we report a
      cofactor, MTA3, a cell type-specific subunit of the corepressor complex Mi
      2/NuRD, for BCL-6-dependent cell fate determination. MTA3 is expressed in the
      same pattern in germinal centers as BCL-6. BCL-6 physically interacts with Mi
      2/NuRD and this interaction is sensitive to BCL-6 acetylation status. Depletion
      of MTA3 by RNAi impairs BCL-6-dependent repression and alters the cell-specific
      transcriptional pattern characteristic of the B lymphocyte. Remarkably, exogenous
      expression of BCL-6 in a plasma cell line leads, in an MTA3-dependent manner, to
      repression of plasma cell-specific transcripts, reactivation of the B cell
      transcriptional program, expression of B lymphocyte cell surface markers, and
      reprogramming of cell fate.

PMID- 15454083
TI  - Temporal control of differentiation by the insulin receptor/tor pathway in
      Drosophila.
AB  - Multicellular organisms must integrate growth and differentiation precisely to
      pattern complex tissues. Despite great progress in understanding how different
      cell fates are induced, it is poorly understood how differentiation decisions are
      temporally regulated. In a screen for patterning mutants, we isolated alleles of
      tsc1, a component of the insulin receptor (InR) growth control pathway. We find
      that loss of tsc1 disrupts patterning due to a loss of temporal control of
      differentiation. tsc1 controls the timing of differentiation downstream or in
      parallel to the RAS/MAPK pathway. Examination of InR, PI3K, PTEN, Tor, Rheb, and
      S6 kinase mutants demonstrates that increased InR signaling leads to precocious
      differentiation while decreased signaling leads to delays in differentiation.
      Importantly, cell fates are unchanged, but tissue organization is lost upon loss
      of developmental timing controls. These data suggest that intricate developmental
      decisions are coordinated with nutritional status and tissue growth by the InR
      signaling pathway.

PMID- 15454084
TI  - Mammalian Ryk is a Wnt coreceptor required for stimulation of neurite outgrowth.
AB  - The Ryk receptor belongs to the atypical receptor tyrosine kinase family. It is a
      new member of the family of Wnt receptor proteins. However, the molecular
      mechanisms by which the Ryk receptor functions remain unknown. Here, we report
      that mammalian Ryk, unlike the Drosophila Ryk homolog Derailed, functions as a
      coreceptor along with Frizzled for Wnt ligands. Ryk also binds to Dishevelled,
      through which it activates the canonical Wnt pathway, providing a link between
      Wnt and Dishevelled. Transgenic mice expressing Ryk siRNA exhibit defects in axon
      guidance, and Ryk is required for neurite outgrowth induced by Wnt-3a and in the
      activation of T cell factor (TCF) induced by Wnt-1. Thus, Ryk appears to play a
      crucial role in Wnt-mediated signaling.

PMID- 15454085
TI  - The PLETHORA genes mediate patterning of the Arabidopsis root stem cell niche.
AB  - A small organizing center, the quiescent center (QC), maintains stem cells in the
      Arabidopsis root and defines the stem cell niche. The phytohormone auxin
      influences the position of this niche by an unknown mechanism. Here, we identify
      the PLETHORA1 (PLT1) and PLT2 genes encoding AP2 class putative transcription
      factors, which are essential for QC specification and stem cell activity. The PLT
      genes are transcribed in response to auxin accumulation and are dependent on
      auxin response transcription factors. Distal PLT transcript accumulation creates
      an overlap with the radial expression domains of SHORT-ROOT and SCARECROW,
      providing positional information for the stem cell niche. Furthermore, the PLT
      genes are activated in the basal embryo region that gives rise to hypocotyl,
      root, and root stem cells and, when ectopically expressed, transform apical
      regions to these identities. Thus, the PLT genes are key effectors for
      establishment of the stem cell niche during embryonic pattern formation.

PMID- 15454086
TI  - Defects in adaptive energy metabolism with CNS-linked hyperactivity in PGC-1alpha
      null mice.
AB  - PGC-1alpha is a coactivator of nuclear receptors and other transcription factors
      that regulates several metabolic processes, including mitochondrial biogenesis
      and respiration, hepatic gluconeogenesis, and muscle fiber-type switching. We
      show here that, while hepatocytes lacking PGC-1alpha are defective in the program
      of hormone-stimulated gluconeogenesis, the mice have constitutively activated
      gluconeogenic gene expression that is completely insensitive to normal feeding
      controls. C/EBPbeta is elevated in the livers of these mice and activates the
      gluconeogenic genes in a PGC-1alpha-independent manner. Despite having reduced
      mitochondrial function, PGC-1alpha null mice are paradoxically lean and resistant
      to diet-induced obesity. This is largely due to a profound hyperactivity
      displayed by the null animals and is associated with lesions in the striatal
      region of the brain that controls movement. These data illustrate a central role
      for PGC-1alpha in the control of energy metabolism but also reveal novel systemic
      compensatory mechanisms and pathogenic effects of impaired energy homeostasis.

PMID- 15454087
TI  - Combinatorial marking of cells and organelles with reconstituted fluorescent
      proteins.
AB  - Expression of GFP and other fluorescent proteins depends on cis-regulatory
      elements. Because these elements rarely direct expression to specific cell types,
      GFP production cannot always be sufficiently limited. Here we show that
      reconstitution of GFP, YFP, and CFP previously split into two polypeptides yields
      fluorescent products when coexpressed in C. elegans. Because this reconstitution
      involves two components, it can confirm cellular coexpression and identify cells
      expressing a previously uncharacterized promoter. By choosing promoters whose
      expression patterns overlap for a single cell type, we can produce animals with
      fluorescence only in those cells. Furthermore, when one partial GFP polypeptide
      is fused with a subcellularly localized protein or peptide, this restricted
      expression leads to the fluorescent marking of cellular components in a subset of
      cells.

PMID- 15454088
TI  - Characterization of acetylcholinesterase expression and secretion during
      osteoblast differentiation.
AB  - Although best known for its role in cholinergic signalling, a substantial body of
      evidence suggests that acetylcholinesterase (AChE) has multiple biological
      functions. Previously, we and others identified AChE expression in areas of bone
      that lacked expression of other neuronal proteins. More specifically, we
      identified AChE expression at sites of new bone formation suggesting a role for
      AChE as a bone matrix protein. We have now characterised AChE expression,
      secretion and adhesive function in osteoblasts. Using Western blot analysis, we
      identified expression of two AChE species in osteoblastic cells, a major species
      of 68 kDa and less abundant species of approximately 55 kDa. AChE colocalised
      with the Golgi apparatus in osteoblastic cells and was identified in osteoblast
      conditioned medium. Further analyses revealed differentiation-dependent secretion
      by osteoblasts, with AChE secretion levels corresponding with alkaline
      phosphatase activity. AChE expression by osteoblastic cells was also found to be
      regulated by mechanical strain both in vitro and in vivo. Finally, we
      investigated the possibility of a functional role for AChE in osteoblast
      adhesion. Using specific inhibitors, blockade of sites thought to be responsible
      for AChE adhesive properties caused a concentration-dependent decrease in
      osteoblastic cell adhesion, suggesting that AChE is involved in regulating cell
      matrix interactions in bone.

PMID- 15454089
TI  - Sclerostin promotes the apoptosis of human osteoblastic cells: a novel regulation
      of bone formation.
AB  - A null mutation in the SOST gene is associated with sclerosteosis, an inherited
      disorder characterized by a high bone mass phenotype. The protein product of the
      SOST gene, sclerostin, is a bone morphogenetic protein (BMP) antagonist that
      decreases osteoblast activity and reduces the differentiation of
      osteoprogenitors. We sought to delineate the mechanism by which sclerostin
      modulated osteoblastic function by examining the effects of the protein on
      differentiating cultures of human mesenchymal stem cells (hMSC). Sclerostin
      significantly decreased alkaline phosphatase (ALP) activity and the proliferation
      of hMSC cells. In addition, hMSC cells treated with sclerostin displayed a marked
      increase in caspase activity. Elevated levels of fragmented histone-associated
      DNA in these cells were detected by ELISA and by TUNEL staining. Other BMP
      antagonists including noggin, Chordin, Gremlin, and Twisted gastrulation did not
      affect caspase activity. The sclerostin-mediated increase in caspase activity was
      blocked by caspase-1 and caspase-3 inhibitors. Sclerostin-induced changes in ALP
      activity and the survival of hMSC cells were partially restored by BMP-6,
      suggesting the involvement of additional growth factors. These findings show that
      sclerostin selectively controls the apoptosis of bone cells. The ability of
      sclerostin to interact with important growth factors such as BMPs likely serves
      as the basis by which it modulates the survival of osteoblasts. By making these
      growth factors unavailable for cell function, sclerostin promotes the apoptosis
      of bone cells, providing a novel level of control in the regulation of bone
      formation.

PMID- 15454090
TI  - Age at first oral contraceptive use as a major determinant of vertebral bone mass
      in female endurance athletes.
AB  - It was the aim of this retrospective analysis to examine the influence of low
      dose monophasic oral contraceptives (OCs) on bone mineral density (BMD) of the
      femoral neck and of the spine in young female endurance athletes. Data on
      training intensity, dietary intake, menarche, menstrual cycle disorders, years of
      OC use, and age at first OC use were determined by a self-report questionnaire.
      Only athletes performing regular endurance exercise for more than 3 years with
      more than 3 h of exercise per week were included in this study and underwent a
      clinical assessment including measurement of weight, height, spine, and hip BMD
      by dual-energy X-ray absorptiometry, and collection of a blood sample. The data
      from 75 regularly exercising endurance athletes aged 18-35 years (26.5 +/- 4.8
      years) were initially included in this analysis. Six athletes were later excluded
      due to oligo-/amenorrhea. Subjects were allocated into the OC group when they
      reported OC use for more than 3 years in women younger than 22 years of age, or
      when they reported OC use for more than 50% of the time after menarche in women
      aged 22-35 years. There were no differences in age, weight, height, body mass
      index (BMI), body fat, menarche, training intensity, age at start of training, or
      any serum parameters between OC users (n = 31) and control subjects (n = 38).
      However, OC users had 7.9% lower spine BMD and 8.8% lower proximal femur BMD (P <
      0.01 for both sites). When the relationship between BMD of the spine and OC use
      was further analyzed by a stepwise model of multiple regression analysis using OC
      years, age at OC initiation, BMI, and menarche as independent variables, age at
      first OC use was found to be the best predictor of vertebral BMD, while the only
      significant predictor of femoral neck BMD was BMI. We conclude that OC use is
      associated with decreased BMD of the spine and the femoral neck in female
      endurance athletes, and that early age at initiation of OC use may be an
      important risk factor for low peak bone mass in young women.

PMID- 15454091
TI  - Adiponectin and its receptors are expressed in bone-forming cells.
AB  - Adiponectin has until now been considered to be synthesized and secreted
      exclusively by the adipose tissue, and is reported to influence energy
      homeostasis and insulin sensitivity. It is also known that body weight is
      positively correlated with increased bone mineral density and decreased fracture
      risk. The mechanisms explaining this relation, however, are not completely
      understood. We report a link between adiponectin and bone homeostasis by
      demonstrating transcription, translation, and secretion of adiponectin, as well
      as expression of its receptors, AdipoR1 and AdipoR2, in bone-forming cells. We
      show that adiponectin and the receptors are expressed in primary human
      osteoblasts from femur and tibia. The phenotype of bone cells was confirmed by
      the high expression levels of alkaline phosphatase, collagen type 1, osteocalcin,
      and CD44, and the formation of mineralization nodules. Immunostaining with
      monoclonal antibodies also demonstrated the presence of adiponectin in human
      osteosarcoma cells and normal osteoblasts. Both mRNA expression and secretion of
      adiponectin to the medium increased during differentiation of human osteoblasts
      in culture. The adiponectin mRNA level increases in osteoblasts cultured 3 and 7
      days in the presence of dietary fatty acids and supplementation of culture medium
      with recombinant adiponectin enhances the proliferation of murine osteoblasts.
      The regulation and detailed function of adiponectin in bone still remains
      obscure, but our findings suggest a functional role in bone homeostasis. If so,
      adiponectin may provide an important signal linking fat and body weight to bone
      density.

PMID- 15454092
TI  - Spontaneous differentiation of mesenchymal stem cells obtained from fetal rat
      circulation.
AB  - Mesenchymal stem cells (MSCs) are thought to be multipotential, capable of
      differentiating into multiple lineages. We attempted to characterize rat cells
      derived from fetal circulating blood (FCBCs) that displayed a fibroblastic
      morphology and differentiated into osteoblastic and chondrocytic lineages.
      Notably, they differentiated into a chondrocyte-specific phenotype on plastic
      culture dishes in medium supplemented only with 10% fetal bovine serum (FBS)
      without the use of a three-dimensional culture substrate. Bone marrow-derived
      cells did not convey such phenotypic expression under the same conditions. The
      characteristic features of these cells were analyzed by reverse transcription
      polymerase chain reaction, immunohistological and von Kossa staining, and by
      immuno-dot blotting. In one population, expression of collagen types II and X was
      detected in differentiated cells at the same levels as observed in chondrocytes
      derived from rat rib cartilage. In another population, parathyroid hormone
      receptor, alkaline phosphatase, and osteocalcin were also expressed at levels
      almost equal to those observed in long bone-derived osteoblasts. After 3 weeks in
      culture, extensively condensed cell masses, stained with anti-type II collagen
      antibody, could be distinguished histologically from small, multilayered, von
      Kossa-positive nodules, which stained with anti-osteocalcin, but not with anti
      type II collagen antibody. In addition, the FCBCs differentiated into adipogenic
      cells in the presence of methyl-isobutyl xanthine, dexamethasone, insulin, and
      indomethacin. These cells expressed PPARgamma2 mRNA and accumulated lipid
      vesicles detectable by Oil red-O staining. Our findings suggest that FCBCs have
      the potential to readily differentiate into multiple lineages and that they are
      distinct from mesenchymal stem cells derived from bone marrow or circulating
      blood from more mature and adults in their spontaneous differentiation in the
      absence of specific factors such as transforming growth factor-beta (TGF-beta) or
      dexamethasone, or a three-dimensional culture environment.

PMID- 15454093
TI  - Long-term effects of neridronate on human osteoblastic cell cultures.
AB  - Bisphosphonates (BPs) are widely used in the treatment of a variety of bone
      related diseases, particularly where the bone turnover is skewed in favor of
      osteolysis. The mechanisms by which BPs reduce bone resorption directly acting on
      osteoclasts are now largely clarified even at molecular level. Researches
      concerning the BP's effects on osteoblast have instead shown variable results.
      Many in vitro studies have reported positive effects on osteoblasts proliferation
      and mineralization for several BPs; however, the observed effects differ,
      depending on the variety of different model system that has been used.
      OBJECTIVES: We have investigated if neridronate, an aminobisphosphonate suitable
      for pulsatory parenteral administration, could have an effect on human
      osteoblastic proliferation and differentiation in vitro. METHODS: We have
      investigated whether prolonged addition of neridronate (from 10(-3) to 10(-11) M)
      to different human osteoblasts cultures, obtained from 14 different bone
      specimens, could affect the cells number, the endogenous cellular alkaline
      phosphatase (ALKP) activity, and the formation of mineralized nodules. RESULTS:
      Our results show that neridronate does not negatively affect in vitro the
      viability, proliferation, and cellular activity of normal human osteoblasts even
      after a long period addition of the drug (20 days) at concentrations equal or
      lower than 10(-5) mol/l (therapeutic dose). In addition, neridronate seems to
      enhance the differentiation of cultured osteoblasts in mature bone-forming cells.
      A maximum increase of alkaline phosphatase activity (+50% after 10 days; P <
      0.01) and mineralized nodules (+48% after 20 days; P < 0.05) was observed in
      cultures treated with neridronate 10(-8) M. CONCLUSIONS: These results encourage
      the use of neridronate in long-term therapy of demineralizing metabolic bone
      disorders.

PMID- 15454094
TI  - Histochemical evaluation for the biological effect of menatetrenone on
      metaphyseal trabeculae of ovariectomized rats.
AB  - To evaluate the biological effects of vitamin K2 (menatetrenone, MK-4) on
      ovariectomy (OVX)-induced bone loss, we have examined histological alterations of
      femoral metaphyses of sham-operated (sham group), ovariectomized (OVX group), and
      MK-4 dietary-supplemented OVX (MK-4 group; 50 mg/kg per day) female Fischer rats
      1, 2, 5, and 8 weeks after OVX. In the first week, rats of the OVX and MK-4
      groups showed discontinuous trabeculae compared with sham-operated rats. At 2
      weeks after OVX, the OVX rats revealed many large tartrate resistant acid
      phosphatase (TRAP)-positive osteoclasts, while osteoclasts in the MK-4-treated
      rats were similar in size to those of the sham group. At 5 weeks, the OVX and MK
      4 groups revealed fragmented trabeculae in femoral metaphyses. The cartilage
      matrix was partially exposed due to stimulated bone resorption in the OVX group,
      but not in the MK-4 group. After 8 weeks, the OVX rats had little metaphyseal
      trabeculae, whereas the MK-4-treated rats had maintained short trabeculae.
      Despite the presence of intense alkaline phosphatase-positive osteoblasts on
      trabeculae in the MK-4 group, TRAP-positive osteoclasts were flattened without
      developing ruffled borders. Therefore, MK-4 appeared to lessen the increase in
      osteoclastic bone resorption induced by OVX, as well as to maintain the
      accelerated osteoblastic activity. It is of importance to identify the target
      cells for MK-4 in bone. Autoradiography localized [3H]-labeled MK-4 mainly in
      osteoblasts and adjacent bone matrices, but not in osteoclasts, indicating that
      MK-4 targets osteoblasts. Thus, MK-4 appears to target osteoblasts, consequently
      inhibiting bone loss induced by ovariectomy.

PMID- 15454095
TI  - Response of the osteocyte syncytium adjacent to and distant from linear
      microcracks during adaptation to cyclic fatigue loading.
AB  - Cyclic loading induces fatigue in bone and initiates a complex, functionally
      adaptive response. We investigated the effect of a single period of fatigue on
      the histologic structure and biomechanical properties of bone. The ulnae of 40
      rats were subjected to cyclic fatigue (-6000 microepsilon) unilaterally until 40%
      loss of stiffness developed, followed by 14 days of adaptation. The contralateral
      ulna served as a treatment control (n = 20 rats), and a baseline loaded/non
      loaded group (n = 20 rats/group) was included. Bones from 10 rats/group were
      examined histologically and the remaining bones (10 rats/group) were tested
      mechanically. The following measurements were collected: volumetric bone mineral
      density (vBMD); ultimate force (Fu); stiffness (S); energy-to-failure (U);
      cortical area (Ct.Ar); microcrack density (Cr.Dn); microcrack mean length
      (Cr.Le); microcrack surface density (Cr.S.Dn); osteocyte density (Ot.N/T.Ar and
      Ot.N/TV); bone volume fraction (B.Ar/T.Ar); resorption space density
      (Rs.N/Ct.Ar); and maximum and minimum area moments of inertia (IMAX and IMIN).
      Using confocal microscopy, the bones were examined for diffuse matrix injury,
      canalicular disruption, and osteocyte disruption. The adapted bones had increased
      B.Ar, IMAX, and IMIN in the mid-diaphysis. Fatigue loading decreased structural
      properties and induced linear microcracking. At 14 days, adaptation restored
      structural properties and microcracking was partially repaired. There was a
      significant nonlinear relationship between Ot.N/T.Ar and B.Ar/T.Ar during
      adaptation. Disruption of osteocytes was observed adjacent to microcracks
      immediately after fatigue loading, and this did not change after the period of
      adaptation. In fatigue-loaded bone distant from microcracks, diffuse matrix
      injury and canalicular disruption were often co-localized and were increased in
      the lateral (tension) cortex. These changes were partially reversed after
      adaptation. Loss of canalicular staining and the presence of blind-ends in
      regions with matrix injury were suggestive of rupture of dendritic cell
      processes. Taken together, these data support the general hypothesis that the
      osteocyte syncytium can respond to cyclic loading and influence targeted
      remodeling during functional adaptation. Changes in the appearance of the
      osteocyte syncytium were found in fatigue-loaded bone with and without linear
      microcracks. We hypothesize that the number of dendritic cell processes that
      experience load-related disruption may determine osteocyte metabolic responses to
      loading and influence targeted remodeling.

PMID- 15454096
TI  - Transplantation of marrow-derived mesenchymal stem cells and platelet-rich plasma
      during distraction osteogenesis--a preliminary result of three cases.
AB  - Clinical results of distraction osteogenesis with transplantation of marrow
      derived mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP) were
      reviewed in three femora and two tibiae of the two patients with achondroplasia
      and one patient with congenital pseudarthrosis of the tibia. MSCs derived from
      the iliac crest were cultured with osteogenic supplements and differentiated into
      osteoblast-like cells. PRP, which is known to contain several growth factors and
      coagulate immediately by a minute introduction of thrombin and calcium, was
      prepared just before transplantation. Culture-expanded osteoblast-like cells and
      autologous PRP were injected into the distracted callus with the thrombin-calcium
      mixture so that the PRP gel might develop within the injected site.
      Transplantation of MSCs and PRP was done at the lengthening and consolidation
      period in each patient. The target lengths were obtained in every leg without
      major complications and the average healing index was 23.0 days/cm (18.8-26.9
      days/cm). Although these results are still preliminary, transplantation of
      osteoblast-like cells and PRP, which seemed to be a safe and minimally invasive
      cell therapy, could shorten the treatment period by acceleration of bone
      regeneration during distraction osteogenesis.

PMID- 15454097
TI  - Adaptation of mechanical, morphological, and biochemical properties of the rat
      growth plate to dose-dependent voluntary exercise.
AB  - Mechanical loading has been shown to modulate longitudinal bone growth and
      cellular activity of the growth plate. Nevertheless, limited and controversial
      results exist regarding the effect of exercise on a physiological level on the
      growth plate. The present study investigated whether dose-dependent voluntary
      exercise has an influence on morphological, biochemical, and mechanical factors
      of the distal femoral growth plate of immature rats. Female growing Sprague
      Dawley rats were randomly assigned to a unlimited exercise group (UE, n = 10), a
      limited exercise group (LE, n = 10), and a sedentary control group (CON, n = 10).
      The exercise groups were trained voluntarily in a running wheel for 8 weeks. The
      UE group could use the running wheel every time, whereas the LE group had timely
      restricted (50%) access. After sacrifice, the right femur was prepared for
      histomorphometric analysis and immunohistochemical staining of the distal growth
      plate. Mechanical testing was carried out on the distal growth plate of the left
      femur in shear direction. At the end of the study, the UE group had a
      significantly lower body mass than the CON group. There was no significant
      difference in overall femoral length between the groups. The height of the growth
      plate and the proliferation zone was significantly greater in the CON group than
      in both exercise groups. Only the LE group had a significantly lower hypertrophic
      zone and matrilin-3 staining pattern than the CON group. Osteonectin was located
      in the matrix of the upper hypertrophic zone in the UE group, whereas the LE and
      CON group showed more chondrocytes in the hypertrophic and lower proliferation
      zones stained for osteonectin, suggesting a higher level of mineralization in the
      growth plate of the UE group. No variations of mechanical properties of the
      distal femoral growth plate were detected. These results clearly demonstrate
      adaptations of morphology and biochemical parameters to the dose of running
      exercise, which do not result in significant differences in mechanical properties
      or bone length between the UE, LE, and CON groups.

PMID- 15454098
TI  - The relative contribution of cysteine proteinases and matrix metalloproteinases
      to the resorption process in osteoclasts derived from long bone and scapula.
AB  - It has been suggested that functional heterogeneity exists between osteoclasts
      from different bone sites. This could be exploited to design therapeutics that
      would selectively inhibit bone resorption only at compromised sites. To further
      investigate the existence of functional differences between osteoclasts from
      different bone sites we assessed whether osteoclasts isolated from
      intramembranous bone differ from osteoclasts isolated from endochondral bone in
      the extent that they utilize cysteine proteinases and matrix metalloproteinases
      to degrade the organic matrix of bone. The differential involvement of the two
      classes of proteases was assessed by analyzing dose-dependent effects of the
      matrix metalloproteinase inhibitor, CT-1746, and of the cathepsin inhibitor, E64,
      on bone resorption. Osteoclasts isolated from the scapula (intramembranous) and
      long bones (endochondral) of newborn New Zealand white rabbits were seeded on
      cortical bovine bone slices in the presence or absence of inhibitors. Resorptive
      activity was evaluated by measuring the number and area of resorption pits and by
      measuring the release of collagen degradation products in the culture medium. In
      the absence of inhibitors, scapular osteoclasts and long bone osteoclasts had
      similar activity based on these criteria. The resorptive activity of scapular
      osteoclasts was inhibited to a greater extent by the MMP inhibitor CT-1746 than
      by the cysteine proteinase inhibitor E64. Conversely, resorption by osteoclasts
      derived from long bones was inhibited to a greater degree by the cysteine
      proteinase inhibitor. These results strongly suggest that there are functional
      differences between dispersed osteoclasts derived from the scapula and long
      bones, with scapular osteoclasts utilizing matrix metalloproteinases to a greater
      extent than cysteine proteinases and long bone osteoclasts using cysteine
      proteinases to a greater extent than matrix metalloproteinases.

PMID- 15454099
TI  - Sensitivity analysis of a novel mathematical model identifies factors determining
      bone resorption rates.
AB  - The development of pharmaceutical treatments for bone disease can be enhanced by
      computational models that predict their effects on resorption and rates of
      remodeling. Therefore, a simple mathematical model was formulated to simulate
      erosion depth and duration of resorption, using Michaelis-Menten (M-M) equations
      to describe changing rates of cellular activity during the two phases of bone
      resorption. The model was based on histomorphometric data and cellular
      interactions that occur in the bone microenvironment cited from the literature.
      Availability of bone substrate for osteoclastic activity during Phase I was
      assumed to be limited by the ratio of RANKL (ligand for receptor activator for
      nuclear factor kappaB) to osteoprotegerin (OPG) ('effective RANKL'). The required
      presence of marrow stromal cell produced macrophage-colony stimulating factor (M
      CSF) for osteoclast action was represented as a factor equal to 1 for healthy
      bone. Growth factors released from the matrix during Phase I were assumed to
      cause two negative feedback effects: (1) the inhibitory effect of transforming
      growth factor-beta1 (TGFbeta1)-induced production of OPG by marrow osteoblast
      stromal cells, reducing effective RANKL; (2) the apoptosis of osteoclast nuclei
      assumed to occur at high concentrations of TGFbeta. This signaled the end of
      Phase I. During Phase II, cellular activity to remove the collagen fibrils left
      behind by osteoclasts was also simulated by Michaelis-Menten kinetic equations.
      Results of sensitivity analysis revealed variation in resorption depth and
      duration to fluctuate within 6% and 7% of the baseline value for changes in most
      input parameters. However, resorption depth was reduced and the duration of
      resorption lengthened by both a decrease in matrix TGFbeta and an increase the
      apoptotic threshold. Furthermore, the duration of resorption, but not erosion
      depth, was sensitive to changes in the maximum rate of cellular activity during
      removal of collagen fibrils. This mathematical model, which simulates the
      changing rates of cellular activity, has identified factors that reduce the
      duration and depth of resorption. It also suggests new targets for modeling
      therapeutic intervention to slow the rate of bone remodeling.

PMID- 15454100
TI  - Bone mineralization density and femoral neck fragility.
AB  - The traditional view of osteoporotic fractures is that they result from a
      reduction in bone mass combined with alterations in the micro-architecture. Apart
      from the effects of bone remodeling, the material properties of the remaining
      bone are thought to be unaffected. To test this, we compared the degree of matrix
      mineralization in femoral neck biopsies taken from cases of intracapsular hip
      fracture with age- and sex-matched postmortem controls. Whole femoral neck
      biopsies from seven female hip fracture cases (72-90 years) and nine controls (68
      94 years) were embedded in methylmethacrylate, and sections stained with
      Solochrome Cyanin R for analysis of osteoid. The blocks were then diamond micro
      milled, carbon coated, and analyzed for the degree of matrix mineralization using
      halogenated dimethacrylate standards for quantitative backscattered electron
      (qBSE) imaging (20 kV, entire block face, sampling interval 5 microm). The BSE
      gray scale was adjusted such that 0 corresponds to an electron backscattering
      coefficient of 0.1159 (approximately 1.70 g/ml) and 255-0.1519 (approximately
      2.18 g/ml). Remodeling and mineralization data were analyzed for both the whole
      biopsy face and on a regional (anterior; inferior, posterior, or superior) basis.
      Over the whole biopsy, the level of mineralization was lower in the cases than
      the postmortem controls (-2.8%, P < 0.05). In both cases and controls, cortical
      mineralization was higher in the inferior (compressive) region compared with
      superior (tensile) region (P < 0.05). Mineralization was lower in all regions of
      the cases (inferior: -3.3%; posterior: -3.1%; anterior: -2.7%; superior: -1.6%)
      compared to the controls. Mineralization density in cancellous bone was not
      regionally dependent but was lower in the fracture cases (-3.5%; P = 0.001).
      Although there were weak relationships between osteoid formation (%O.Ar/B.Ar) and
      the mean level of mineralization in both cortical (P = 0.068) and cancellous (P <
      0.01) bone, adjustment for this did not markedly affect the case-control
      differences. In conclusion, this study has shown that in cases of intracapsular
      hip fracture, matrix mineralization is reduced in the femoral neck. Unexpectedly,
      in view of the likely role of mild to moderate vitamin D deficiency osteopathy in
      hip fracture, this decreased mineralization was independent of osteoid indices
      and therefore potentially independent of bone age. This raises the possibility
      that alterations in the bone matrix such as excessive glycation or changes in the
      composition of the collagen fibrils affect its mineralization in hip fracture
      cases.

PMID- 15454101
TI  - Effects of parathyroidectomy on lead mobilization from bone in patients with
      primary hyperparathyroidism.
AB  - Since lead (Pb) accrued from environmental exposure accumulates in bone with a
      half life time between 6 and 10 years, a release of bone Pb into the circulation
      and/or urine (PbU) should be expected in diseases with increased bone metabolism
      such as hyperparathyroidism. We studied 60 patients with primary
      hyperparathyroidism (pHPT, 50 women, 10 men, aged 61.4 +/- 10.6 and 64.1 +/- 9.9
      years, respectively) (a) before, (b) 1-6 months, and (c) 6-12 months after
      parathyroidectomy. Besides lead in blood (PbB) and lead in 24-h urine samples
      (PbU), parathyroid hormone (PTH), serum Ca2+, osteocalcin (OC), phosphate (PO4),
      and serum pyridinoline cross-linked telopeptide (cTP) were determined. Control
      data were determined in 20 healthy age-matched subjects. As expected, Ca2+
      decreased after parathyroidectomy. Mean PbB in patients with pHPT was in the same
      range as in controls. A decrease of PbB after parathyroidectomy was found in the
      interval beyond 6 months. In contrast, mean PbU initially increased after surgery
      (3.05 +/- 1.94 vs. 4.25 +/- 2.65 microg/l, P = 0.004) and was not different
      beyond 6 months in comparison with preoperative values at (c). Investigating only
      patients with PTH < 150 ng/l, no significant PbB or PbU alterations were detected
      before and after parathyroidectomy. In patients with PTH > 150 ng/l, the decrease
      of PbB at (c) was more pronounced as was the increase of PbU at (b). In these
      patients, PbB and OC as well as PbB and cTP were correlated preoperatively. In
      conclusion, our data show that in environmentally lead-exposed (by food or by
      pollution) hyperparathyroid individuals, there is no hazardous PbB release from
      bone. The preoperative correlation between PbB and OC in pHPT patients with PTH >
      150 ng/l provides evidence that in fact there is a Pb release from bone into the
      blood-pool by bone remodeling. The increase of PbU after parathyroidectomy is
      suspected to be caused by PTH-dependent Pb accumulation in the kidney, which
      seems to be restored with decreasing PTH. Moreover, our data confirm prior
      findings that bone remodeling seems to be normalized 6 months after
      parathyroidectomy.

PMID- 15454102
TI  - Bone response to mechanical loading in adult rats with collagen-induced
      arthritis.
AB  - To elucidate the effects of inflammation on the response of bone to mechanical
      stress, we performed experiments using a rat with collagen-induced arthritis
      (CIA) model. Six-month-old female Wistar rats were used in the experiment. Bovine
      type II collagen sensitization and additional sensitization after 1 week were
      preformed in all CIA groups. Loads were applied using a four-point bending
      device. The right tibia was loaded in both CIA and control (CONT) groups at 35 N
      (low groups), 40 N (medium groups), or 47 N (high groups) for 36 cycles at 2 Hz
      three times per week for 3 weeks. Histomorphometrical data were collected from
      the periosteal and endosteal surfaces of the tibia in all rats. The tibia
      periosteal surface was subdivided into lateral and medial surfaces. Formation
      surface (FS), mineral apposition rate (MAR) and bone formation rate (BFR) were
      calculated. At lateral surface of periosteal surface, all three parameters showed
      significant differences between the loaded and nonloaded tibiae. All these
      parameters were significantly lower in CIA groups than in CONT groups, and
      interaction was seen between applied loading and CIA. There was a significant
      correlation between peak strain and the right-left difference of FS in the CONT
      groups. At medial surface of periosteal surface, there were force-related
      increase in FS, MAR, and BFR on the loaded side in both CIA and CONT groups,
      except MAR in the CONT group. All three parameters showed significant differences
      between the loaded and nonloaded tibiae. At endocortical surface, force-related
      increase was observed only in FS on the loaded side in CONT groups, and FS was
      significantly higher on the loaded side than the nonloaded side. CIA lowered all
      three parameters significantly. We examined the response to mechanical loading on
      the tibia in untreated CONT rats and rats with CIA by bone histomorphometry, and
      found that arthritis suppressed bone formation induced by mechanical loading.

PMID- 15454103
TI  - Methylenetetrahydrofolate reductase polymorphism interacts with riboflavin intake
      to influence bone mineral density.
AB  - Bone mineral density is a complex trait regulated by an interaction between
      genetic and environmental factors. Recent studies have identified a functional
      polymorphism affecting codon 677 of the methylenetetrahydrofolate reductase
      (MTHFR) gene that is associated with reduced bone mineral density (BMD) in
      Japanese and Danish postmenopausal women and increased risk of fracture in
      elderly Danish women. Since dietary B vitamins can influence circulating
      homocysteine (tHcy) levels, we examined the relationship among MTHFR genotype, B
      complex vitamins (folate, vitamin B12, vitamin B6 and riboflavin), BMD, and rate
      of change in BMD in a longitudinal study of 1241 Scottish women aged 45-54 years,
      at the time of initial study, who were followed up for a mean (SD) of 6.6 (0.7)
      years. There was no significant association between BMD and either MTHFR genotype
      or B complex vitamins when examined separately. However, we detected a
      significant interaction among quartile of energy-adjusted riboflavin intake,
      MTHFR 'TT' genotype, and BMD (P = 0.01 for baseline FN BMD, P = 0.02 for follow
      up FN BMD). Increasing dietary riboflavin intake correlated with LS BMD and FN
      BMD in homozygotes for the MTHFR 'T' allele, which remained significant for FN
      after adjustment for confounders (r = 0.192, P = 0.036 for baseline; r = 0.186, P
      = 0.043 at follow-up) but not in the other genotypes. This raises the possibility
      that riboflavin intake and MTHFR genotype might interact to regulate BMD. Further
      work is required to determine if this association holds true for other
      populations and ethnic groups.

PMID- 15454104
TI  - The relationship between lean body mass and bone mineral content in paediatric
      health and disease.
AB  - INTRODUCTION: The correct interpretation of DXA data is critical to the diagnosis
      and management of children with suspected bone disease. This study examines the
      various influences on bone mineral content (BMC), as measured by dual-energy X
      ray absorptiometry (DXA). MATERIALS AND METHODS: Six hundred and forty-six
      healthy school children and forty-three children with chronic diseases, aged 5-18
      years, had their lumbar spine and whole body measured using a Lunar DPX-L DXA
      scanner. RESULTS: Stepwise linear regression identified lean body mass (LBM) as
      the strongest single predictor of BMC in the lumbar spine and the total body. A
      significant gender difference was observed in the relationship between BMC and
      LBM with girls having significantly more bone per unit LBM from 9 years of age in
      the spine and 13 years of age in the total body. To investigate the relationship
      between LBM and BMC in children with chronic disease, a two-stage algorithm based
      upon calculation of Z scores from the normative data was applied. Stage 1
      assessed LBM for height and stage 2 assessed BMC for LBM. Ten children with
      spinal muscular atrophy had a mean LBM for height Z score of -1.8(1.4) but a mean
      BMC for LBM Z score of 1.2(1.3) indicating their primary abnormality was reduced
      muscle mass (sarcopenia) with no evidence of osteopenia. In contrast, 21 children
      with osteogenesis imperfecta had a mean LBM for height Z score of 0.4(1.7) but a
      mean BMC for LBM Z score of -2.5(1.8) indicating normal LBM for size but
      significantly reduced BMC for LBM (i.e. osteopenia) confirming a primary bone
      abnormality. A third group consisting of 12 children with low trauma fractures
      demonstrated little evidence of sarcopenia [mean LBM for height Z score 
      1.1(2.1)] but significant osteopenia [mean BMC for LBM Z score -1.9(1.5)].
      CONCLUSION: The results from this study demonstrate how the relationship between
      height and lean body mass, and lean body mass and bone mineral content can be a
      useful method of diagnosing osteoporosis in children and how the relationships
      can be used to identify if the primary abnormality is in muscle or bone.

PMID- 15454105
TI  - Sexual dimorphism of the femoral neck during the adolescent growth spurt: a
      structural analysis.
AB  - Before puberty, there are only small sex differences in body shape and
      composition. During adolescence, sexual dimorphism in bone, lean, and fat mass
      increases, giving rise to the greater size and strength of the male skeleton. The
      question remains as to whether there are sex differences in bone strength or
      simply differences in anthropometric dimensions. To test this, we applied hip
      structural analysis (HSA) to derive strength and geometric indices of the femoral
      neck using bone densitometry scans (DXA) from a 6-year longitudinal study in
      Canadian children. Seventy boys and sixty-eight girls were assessed annually for
      6 consecutive years. At the femoral neck, cross-sectional area (CSA, an index of
      axial strength), subperiosteal width (SPW), and section modulus (Z, an index of
      bending strength) were determined, and data were analyzed using a hierarchical
      (random effects) modeling approach. Biological age (BA) was defined as years from
      age at peak height velocity (PHV). When BA, stature, and total-body lean mass (TB
      lean) were controlled, boys had significantly higher Z than girls at all maturity
      levels (P < 0.05). Controlling height and TB lean for CSA demonstrated a
      significant independent sex by BA interaction effect (P < 0.05). That is, CSA was
      greater in boys before PHV but higher in girls after PHV. The coefficients
      contributing the greatest proportion to the prediction of CSA, SPW, and Z were
      height and lean mass. Because the significant sex difference in Z was relatively
      small and close to the error of measurement, we questioned its biological
      significance. The sex difference in bending strength was therefore explained by
      anthropometric differences. In contrast to recent hypotheses, we conclude that
      the CSA-lean ratio does not imply altered mechanosensitivity in girls because
      bending dominates loading at the neck, and the Z -lean ratio remained similar
      between the sexes throughout adolescence. That is, despite the greater CSA in
      girls, the bone is strategically placed to resist bending; hence, the bones of
      girls and boys adapt to mechanical challenges in a similar way.

PMID- 15454106
TI  - Bone metabolism in galactosemia.
AB  - Classical galactosemia is an autosomal recessively inherited disorder of
      galactose metabolism. Treatment consists of life-long dietary restriction of
      galactose. Despite treatment, long-term complications occur such as a decreased
      bone mineral density (BMD). A decreased BMD might be the result of either dietary
      deficiencies secondary to the galactose-restricted diet or unknown intrinsic
      factors. In this study, 40 children with classical galactosemia (13 males and 27
      females, aged 3-17 years) on dietary treatment were included to gain insight in
      the bone metabolism of galactosemics. We found weight and height Z scores
      significantly decreased in galactosemics. Mean areal BMD Z scores of lumbar spine
      and of femoral neck as measured by Dual energy X-ray Absorptiometry (DXA) were 
      0.6 (P < 0.001) and -0.3 (P = 0.066), respectively. Mean volumetric BMD of the
      femoral neck was significant lower in galactosemics (P < 0.001). The recommended
      dietary allowances (RDA) for calcium, magnesium, zinc, vitamin D, and protein
      were met in all patients. Mean serum levels of calcium, phosphate, magnesium,
      zinc, 1,25-dihydroxy vitamin D (1,25OHD), parathormone (PTH), 17-beta estradiol,
      bone alkaline phosphatase (BAP), and under-carboxylated osteocalcin (ucOC) were
      normal. Serum levels of IGF-1 Z score, carboxylated osteocalcin (cOC), N-terminal
      telopeptide (NTX), and C-terminal telopeptide (CTX) were significantly lower in
      galactosemics than in control subjects. The different bone markers were strongly
      correlated. The low levels of IGF-1 Z score, formation marker cOC, and resorption
      markers NTX and CTX suggest a decreased bone metabolism in galactosemics.

PMID- 15454107
TI  - Increased bone density associated with DLX3 mutation in the tricho-dento-osseous
      syndrome.
AB  - Tricho-dento-osseous syndrome (TDO) (OMIM #190320) is an autosomal dominant
      disorder characterized and named for the three most commonly affected tissues
      hair, teeth, and bones. Common to all individuals with TDO studied to date is a
      four base-pair deletion in the DLX3 gene on chromosome 17q21. This mutation is
      associated with a variable bone phenotype that includes alteration in
      intramembranous bone formation in the skull. The purpose of this study was to
      characterize and compare endochondral bone phenotypes and variability at central
      and peripheral locations of the skeleton by evaluating bone density in
      individuals having the same DLX3, 4 bp DEL,NT3198 mutation (OMIM 600525) and non
      affected family members using dual-energy x-ray absorptiometry (DEXA). Thirty
      four individuals (20 TDO-affected and 14 non-affected) participated in this
      prospective study. All participants were evaluated for the DLX3 mutation
      associated with TDO. All subjects received DEXA scans at common, literature
      supported osteoporotic test regions including: (1) non-dominant distal
      radius/ulna, (2) femoral neck, and (3) lumbar spine L2-4. There was a significant
      increase (P < 0.05) in bone mineral density in TDO-affected individuals compared
      with control individuals at each test region. The markedly increased bone density
      in individuals having the DLX3, 4 bp DEL,NT3198 mutation shows that this
      alteration affects both endochondral and intramembranous bone formation and
      suggests that the DLX3 gene is important in bone formation and/or homeostasis of
      the appendicular skeleton.

PMID- 15454108
TI  - Does hip strength measures account for the difference in hip fracture incidence
      between the Chinese and Caucasian populations?

PMID- 15454110
TI  - Effect of Tinospora cordifolia on the cytokine profile of angiogenesis-induced
      animals.
AB  - The antiangiogenic activity of Tinospora cordifolia was studied using in vivo as
      well as in vitro models. In vivo antiangiogenic activity was studied using B16F10
      melanoma cell-induced capillary formation in animals. Intraperitoneal
      administration of the extract at a concentration of 20 mg/kg significantly
      inhibited the tumour directed capillary formation induced by melanoma cells.
      Analysis of the serum cytokine profile showed a drastic increase of
      proinflammatory cytokines such as IL-1beta, IL-6, TNF-alpha, granulocyte monocyte
      colony stimulating factor (GM-CSF) and the direct endothelial cell proliferating
      agent vascular endothelial cell growth factor (VEGF) in the angiogenesis-induced
      control animals. Administration of Tinospora extract could differentially
      regulate these cytokine's elevation. The differential regulation is further
      evidenced by the increased production of antiangiogenic agents IL-2 and tissue
      inhibitor of metalloprotease-1 (TIMP-1) in the B16F10-injected, extract-treated
      animals. Moreover, using an in vitro rat aortic ring assay, it was observed that
      the extract at nontoxic concentrations inhibited the production of proangiogenic
      factors from B16F10 melanoma cells. Direct treatment of the extract also inhibits
      the microvessel outgrowth from the aortic ring. Hence, the observed
      antiangiogenic activity of the plant T. cordifolia is related, at least in part,
      to the regulation of the levels of these cytokines and growth factors in the
      blood of the angiogenesis-induced animal.

PMID- 15454111
TI  - Bovine dialyzable leukocyte extract protects against LPS-induced, murine
      endotoxic shock.
AB  - The pathophysiology of endotoxic shock is characterized by the activation of
      multiple pro-inflammatory genes and their products which initiate the
      inflammatory process. Endotoxic shock is a serious condition with high mortality.
      Bovine dialyzable leukocyte extract (bDLE) is a dialyzate of a heterogeneous
      mixture of low molecular weight substances released from disintegrated leukocytes
      of the blood or lymphoid tissue obtained from homogenized bovine spleen. bDLE is
      clinically effective for a broad spectrum of diseases. To determine whether bDLE
      improves survival and modulates the expression of pro-inflammatory cytokine genes
      in LPS-induced, murine endotoxic shock, Balb/C mice were treated with bDLE (1 U)
      after pretreatment with LPS (17 mg/kg). The bDLE improved survival (90%),
      suppressed IL-10 and IL-6, and decreased IL-1beta, TNF-alpha, and IL-12p40 mRNA
      expression; and decreased the production of IL-10 (P<0.01), TNF-alpha (P<0.01),
      and IL-6 (P<0.01) in LPS-induced, murine endotoxic shock. Our results demonstrate
      that bDLE leads to improved survival in LPS-induced endotoxic shock in mice,
      modulating the pro-inflammatory cytokine gene expression, suggesting that bDLE is
      an effective therapeutic agent for inflammatory illnesses associated with an
      unbalanced expression of pro-inflammatory cytokine genes such as in endotoxic
      shock, rheumatic arthritis and other diseases.

PMID- 15454112
TI  - Differential expression of dendritic cell markers by all-trans retinoic acid on
      human acute promyelocytic leukemic cell line.
AB  - Dendritic cells (DCs) are the most potent antigen-presenting cells (APCs) for
      naive T cells and play an important role in cancer immunology. All-trans retinoic
      acid (ATRA) is known to be a differentiating agent in the treatment of acute
      promyelocytic leukemia (APL). In this study, we investigated whether ATRA can
      differentiate the retinoic acid (RA)-sensitive promyelocytic leukemic cell line,
      NB4, to DC-like cells and whether these differentiated cells can activate T
      cells. NB4 cells were differentiated to myeloid cells by 4, 6, and 8 days of ATRA
      treatment. NB4 cells up-regulated markers found in DCs, including HLA-DR,
      costimulatory molecules (CD80 and CD86), adhesion molecules (CD40), and chemokine
      receptors (CCR6) when cultured for 8 days in the presence of 1 microM ATRA.
      Upregulation of CD83 was also detected on the surface of ATRA-treated NB4 cells
      versus untreated cells. The addition of cytokines alone, such as GM-CSF or CD40
      ligand, did not affect the expression of CD83 in untreated NB4 cells but they up
      regulated CD83 in ATRA-treated cells. CD11b was coexpressed with CD80, CD83, and
      CD86 in ATRA-treated NB4 cells. In a functional assay, ATRA-treated NB4 cells
      stimulated T cell proliferation when challenged with Staphylococcus enterotoxin
      B. These results suggest that the differentiation of NB4 cells by ATRA causes the
      cells to express DC markers, and that ATRA-differentiated NB4 cells are able to
      present antigens to T cells.

PMID- 15454113
TI  - Phosphatidic acid and tumor necrosis factor-alpha induce the expression of CD83
      through mitogen activated protein kinase pathway in a CD34+ hematopoietic
      progenitor cell line, KG1.
AB  - To elucidate the signaling pathways involved in the expression of CD83, which is
      linked to the differentiation and maturation states of dendritic cells, we
      examined the effect of phosphatidic acid (PA) on the expression of CD83 in KG1, a
      CD34(+) hematopoietic progenitor cell. In the presence of tumor necrosis factor
      (TNF)-alpha, PA but not lyso-PA up-regulated CD83 on KG1 cells. Moreover, PA and
      TNF-alpha-induced expression of CD83 was slightly increased by propranolol, an
      inhibitor of PA phosphohydrolase but was unaffected by phospholipase A2
      inhibitor. PA and TNF-alpha increased the phosphorylation of extracellular signal
      regulated kinase (ERK)-1/2, p38-kinase, and c-Jun N-terminal kinase (JNK) by
      Western blotting. However, the up-regulation of CD83 by PA/TNF-alpha on KG1 was
      significantly abrogated by PD98059, a specific inhibitor of ERK kinase, but was
      enhanced by SP600125, a JNK inhibitor. Bis-indolylmaleimide, an inhibitor of
      protein kinase C, partially blocked the up-regulation of CD83 and ERK
      phosphorylation induced by PA and TNF-alpha. Moreover, the incubation of KG1
      cells with phorbol ester and TNF-alpha for 5 days increased the protein level of
      phospholipase D. These results suggest that PA and TNF-alpha induce the up
      regulation of CD83 and that their action is regulated by ERK and JNK.

PMID- 15454114
TI  - Study of interaction between the polyoxidonium immunomodulator and the human
      immune system cells.
AB  - Polyoxidonium (PO) is a high-molecular weight physiologically active compound
      with pronounced immunomodulating activity, an N-oxidized polyethylene-piperazine
      derivative. The aim of our work was to study cellular and molecular mechanisms of
      the action of PO on the human peripheral blood leukocytes. By means of flow
      cytometry it was established that the binding of fluorescein-isothiocyanate
      labeled PO (FITC-labeled PO) occurs more rapidly with monocytes and neutrophils
      than with lymphocytes (7- to 8-fold weaker as compared with monocytes). Using
      colloidal gold-labeled PO and electron microscopy it was shown with that the
      preparation penetrates into leukocytes by endocytosis. PO is localized in
      endoplasmic vesicles of cellular cytosol. Analysis of one of the crucial signal
      transducer, the intracellular Ca(2+), performed with the Fluo-3 fluorescent dye,
      showed that PO does not induce Ca(2+) mobilization from the intracellular calcium
      stores and influx of extracellular Ca(2+). The study of the intracellular
      hydrogen peroxide (H(2)O(2)) production with the 2',7'-dichlorfluorescein
      indicator demonstrated that PO significantly increases the level of intracellular
      H(2)O(2) in monocytes and neutrophils, however, this increase is much less as
      compared with phorbol myristate acetate stimulation. The analysis of
      immunomodulating effect produced by PO proved its stimulating activity on some
      cytokines production in vitro, e.g. interleukin 1beta (IL-1beta), tumor necrosis
      factor (TNF)-alpha and IL-6. A dose-dependent increase in the intracellular
      killing by blood phagocytes was established under the action of PO.

PMID- 15454115
TI  - Effects and mechanisms of FR167653, a dual inhibitor of interleukin-1 and tumor
      necrosis factor, on adjuvant arthritis in rats.
AB  - Effects and mechanisms of FR167653, 1-[7-(4-fluorophenyl)-1,2,3,4-tetrahydro-8-(4
      pyridyl)pyrazolo[5,1-c][1,2,4] triazin-2-yl]-2-phenylethanedione sulfate
      monohydrate, a dual inhibitor of interleukin-1 (IL-1) and tumor necrosis factor
      alpha (TNF-alpha), on rat adjuvant arthritis (AA) was investigated. Complete
      Freund's adjuvant was used to induce AA in rats. Secondary paw swelling of AA
      rats was measured, and polyarthritis index was scored. Synoviocytes were
      separated by the method of collagenase and DNase digestion. Synoviocytes
      proliferation was assayed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide (MTT) assay. TNF-alpha, IL-1 and interleukin-10 (IL-10) production of
      synoviocytes was measured with ELISA. The expression of IL-10 mRNA of
      synoviocytes was determined using RT-PCR. There were significant secondary
      inflammatory reactions in AA rats, which accompanied with the decrease of body
      and immune organs weight simultaneously. The administration of FR167653 (4, 12,
      36 mg/kg, subcutaneously (s.c.)) inhibited the inflammatory response and restored
      the weight of body and immune organs of AA rats. Synoviocytes proliferation of AA
      rats significantly increased, and the levels of TNF-alpha and IL-1 in
      supernatants of synoviocytes in AA rats were also elevated compared with the sham
      group. The administration of FR167653 (4, 12, 36 mg/kg, s.c.) reduced the above
      changes significantly. In contrast to TNF-alpha and IL-1, IL-10 production and
      the level of its mRNA of synoviocytes in AA rats were apparently decreased.
      FR167653 (4, 12, 36 mg/kg, s.c.) markedly increased IL-10 in synoviocytes at
      protein and transcription level. The results indicated that FR167653 had a
      beneficial effect on rats AA due to modulating inflammatory cytokines production
      of synoviocytes, which played a crucial role in pathogenesis of this disease.

PMID- 15454116
TI  - Glycyrrhizin and related compounds down-regulate production of inflammatory
      chemokines IL-8 and eotaxin 1 in a human lung fibroblast cell line.
AB  - Glycyrrhizin (GL) is known to have various immunomodulating activities and has
      long been used clinically as an anti-allergic and anti-hepatitis agent. While the
      potency of GL against lung inflammatory diseases has been expected, the effect of
      GL on the lung has been poorly understood. Lung fibroblasts are known as a potent
      producer of inflammatory chemokines, IL-8 and eotaxin 1, by which neutrophils and
      eosinophils are strongly attracted during inflammation. Therefore, we studied the
      effects of GL on the production of these chemokines using a human fetal lung
      fibroblast cell line, HFL-1, stimulated with TNF-alpha and IL-4. Moreover, we
      examined the structure-activity relationships of GL to explore more beneficial
      compounds. 18alpha,beta-GL inhibited IL-8 dose-dependently and inhibited eotaxin
      1 slightly. 18alpha,beta-Glycyrrhetic acid (GA) did not inhibit IL-8 but
      inhibited eotaxin 1. The effect of 18alpha,beta-glycyrrhetic acid monoglucuronide
      (MGA) resembled that of 18alpha,beta-GL but was weaker. Both 3beta-[(2-O-beta-D
      glucopyranuronosyl-beta-D-glucopyranuronosyl)oxy]-18beta-11-deoxo-olean-12-en-30
      oic acid (11-deoxo-GL) and 3beta-[(2-O-beta-D-glucopyranuronosyl-beta-D
      glucopyranuronosyl)oxy]-olean-11,13,(18)-dien-30-oic acid (hetero-GL) exhibited
      inhibitory activity with significant cytotoxicity. 3beta-[(2-O-beta-D
      Glucopyranuronosyl-beta-D-glucopyranuronosyl)oxy]-18beta-olean-9,12-dien-30-oic
      acid (homo-GL) did not have cytotoxicity but its activity was mild like that of
      18alpha,beta-GL. 3beta-[(2-O-beta-d-Glucopyranuronosyl-beta-D
      glucopyranuronosyl)oxy]-olean-11,13(18)-dien-30-ol (hetero-30-OH-GL) and 3beta
      [(2-O-beta-D-glucopyranuronosyl-beta-D-glucopyranuronosyl)oxy]-18beta-olean-9,12
      dien-30-ol (homo-30-OH-GL) showed potent inhibitory effects, at concentrations
      lower than 18alpha,beta-GL with no significant cytotoxicity. These results
      suggest that GL-related compounds are effective in reducing chemokine production
      and that GL-modified compounds including hetero-30-OH-GL and homo-30-OH-GL appear
      most beneficial in view of their inhibitory capacity with less cytotoxicity.

PMID- 15454117
TI  - Immune stimulating properties of a novel polysaccharide from the medicinal plant
      Tinospora cordifolia.
AB  - An alpha-D-glucan (RR1) composed of (1-->4) linked back bone and (1-->6) linked
      branches with a molecular mass of >550 kDa and exhibiting unique immune
      stimulating properties is isolated and characterized from the medicinal plant
      Tinospora cordifolia. This novel polysaccharide is noncytotoxic and
      nonproliferating to normal lymphocytes as well as tumor cell lines at 0-1000
      microg/ml. It activated different subsets of the lymphocytes such as natural
      killer (NK) cells (331%), T cells (102%), and B cells (39%) at 100 microg/ml
      concentration. The significant activation of NK cells is associated with the dose
      dependent killing of tumor cells by activated normal lymphocytes in a functional
      assay. Immune activation by RR1 in normal lymphocytes elicited the synthesis of
      interleukin (IL)-1beta (1080 pg/ml), IL-6 (21,833 pg/ml), IL-12 p70 (50.19
      pg/ml), IL-12 p40 (918.23 pg/ml), IL-18 (27.47 pg/ml), IFN- gamma (90.16 pg/ml),
      tumor necrosis factor (TNF)-alpha (2225 pg/ml) and monocyte chemoattractant
      protein (MCP)-1 (2307 pg/ml) at 100 microg/ml concentration, while it did not
      induce the production of IL-2, IL-4, IL-10, interferon (IFN)-alpha and TNF-beta.
      The cytokine profile clearly demonstrates the Th1 pathway of T helper cell
      differentiation essential for cell mediated immunity, with a self-regulatory
      mechanism for the control of its overproduction. RR1 also activated the
      complements in the alternate pathway, demonstrated by a stepwise increase in C3a
      des Arg components. Incidentally, RR1 stimulation did not produce any oxidative
      stress or inducible nitric oxide synthase (iNOS) in the lymphocytes or any
      significant increase in nitric oxide production. The water solubility, high
      molecular mass, activation of lymphocytes especially NK cells, complement
      activation, Th1 pathway-associated cytokine profile, together with a low level of
      nitric oxide synthesis and absence of oxidative stress confer important
      immunoprotective potential to this novel alpha-D-glucan.

PMID- 15454118
TI  - Evaluation of immunotoxic and immunodisruptive effects of inorganic arsenite on
      human monocytes/macrophages.
AB  - A trivalent inorganic arsenic, arsenite, has been causing chronic inflammation in
      humans through the consumption of contaminated well water. The total peripheral
      blood arsenic concentrations of chronic arsenic-exposed patients, who had
      inflammatory-like immune responses, are less than 1 microM, thus, nM
      concentrations may be very important regarding the chronic inflammatory effects
      by arsenite. However, there are few reports about the biological effects of low
      concentrations of arsenite in mammalian cells, especially in normal immune
      effector cells. In this study, we examined whether arsenite has any biological
      and/or toxicological effects on the differentiation of human peripheral blood
      monocytes into macrophages using the colony-stimulating factor (CSF) in vitro
      compared with that of other metallic compounds, and found that arsenite
      sensitively inhibited the CSF-induced in vitro maturation of monocytes into
      macrophages at nM levels, and it also induced small, nonadhesive and CD14
      positive abnormal macrophage generation from monocytes with granulocyte
      macrophage CSF (GM-CSF) at 50-500 nM without cell death. The addition of other
      metallic compounds, including chromium, selenium, mercury, cadmium, nickel,
      copper, zinc, cobalt, manganese and other human pentavalent arsenic metabolites,
      such as inorganic arsenate, monomethylarsonic acid and dimethylarsinic acid,
      could not induce the same abnormal cell generation from monocytes with CSFs at
      any concentration and any additional time schedules; they showed only simple
      cytolethality in monocytes and macrophages at n-mM levels accompanied by cell
      death. This work may have implications in the arsenic-induced chronic
      inflammation in humans.

PMID- 15454119
TI  - Nicotine could augment adhesion molecule expression in human endothelial cells
      through macrophages secreting TNF-alpha, IL-1beta.
AB  - Nicotine, the major immunomodulatory components of cigarette smoking, is among
      the leading risk factors in atherosclerosis and various other diseases. The
      subject of this study is to observe how nicotine affects the function of
      macrophages and vascular endothelial cells. The changes of nicotine on releasing
      of cytokines from Ana-1 were detected by radio-immunoassay (RIA) or enzyme-link
      immunosorbent assay (ELISA). The adhesion of monocytes to human umbilical vein
      endothelial cells (HUVECs) with Ana-1 supernatant-activated was evaluated through
      adhesion experiments. ELISA and RT-PCR methods examined expression of soluble
      adhesion molecular protein and their mRNA. Which cytokines in Ana-1 supernatant
      affecting HUVECs ability to express adhesion molecular were tested by adhesion
      blockade analysis and ELISA. The results showed TNF-alpha, IL-1beta could reach
      the peak with 0.06mM nicotine treated for 24 and 12 h on Ana-1, respectively, but
      IL-8 and IFN-gamma had no significant alter. Adhesion experiments proved
      treatment of HUVECs with supernatant of Ana-1 for 24 h obviously augmented the
      adhesion of monocytes to HUVECs. ELISA and PCR demonstrated expression of soluble
      intracellular adhesion molecule-1 protein (sICAM-1) increased sharply at 24 h,
      while soluble vascular cell adhesion molecule-1 protein (sVCAM-1) and soluble
      endothelial selectin protein (sE-selectin) rose at 9 h; ICAM-1, VCAM-1 and E
      selectin mRNA had a similar tendency. Treatment of HUVECs with anti-TNF-alpha,
      anti-IL-1beta antibodies pre-neutralized supernatant of Ana-1 could block
      monocytes adhesion. In conclusion, our findings suggest that nicotine could
      augment macrophages releasing TNF-alpha and IL-1beta, furthermore TNF-alpha and
      IL-1beta could up-regulate the expression of adhesion molecule and increase
      adhesion of monocytes to HUVECs. These might be one of the reasons that leaded to
      endothelial dysfunction.

PMID- 15454120
TI  - Concentration-dependent activity of mometasone furoate and dexamethasone on blood
      eosinophils isolated from atopic children: modulation of Mac-1 expression and
      chemotaxis.
AB  - Treatment of asthma with corticosteroids results in downregulation of
      eosinophilic airway inflammation. We evaluated in vitro the activity of an
      "inhaled" corticosteroid, mometasone furoate (MF), and of a "systemic"
      corticosteroid, dexamethasone (DEX), on eosinophil functions, i.e. adhesion
      molecule expression and cell chemotaxis. Partially purified blood eosinophils
      were obtained from 18 asthmatic subjects sensitized to house dust mites. The
      expression of the macrophage antigen (Mac)-1 (CD11b/CD18) was measured by
      specific monoclonal antibody (mAb) staining and flow cytometry analysis at
      baseline or after stimulation with N-formyl-methionyl-leucyl-phenylalanine (fMLP)
      or with recombinant human (rh) granulocyte macrophage-colony stimulating factor
      (GM-CSF) plus a mAb anti-human (ah) IgE low affinity receptor [FcepsilonRII or
      CD23]. Cell chemotaxis toward the complement fragment 5a (C5a) or rh interleukin
      (IL)-5 was evaluated in Boyden microchambers by light microscopy. Eosinophils
      showed a significant increase in Mac-1 expression after activation with fMLP or
      with rh GM-CSF plus ah CD23 mAbs (p<0.05, each comparison) and a remarkable
      chemotactic response to both C5a or rh IL-5 (p<0.001, each comparison). To test
      the inhibitory activity of MF and DEX on eosinophil functions, the cells were
      preincubated for 3 h with four concentrations (0.1, 1, 10 and 100 nM) of each of
      the two drugs, before being activated by fMLP or by rh GM-CSF plus ah CD23 mAbs
      or tested with C5a or with rh IL-5. Independently of the stimulus used, both Mac
      1 expression and eosinophil migration were effectively downregulated by
      preincubation with MF or DEX at 1, 10 and 100 nM (p<0.05). The inhibitory
      activity on cell chemotaxis in response to both C5a or with rh IL-5 was higher
      for MF than DEX, but only at the highest concentration tested (p<0.05, each
      comparison). These data demonstrate that concentrations of MF similar to those
      obtained in vivo are highly effective in inhibiting eosinophil functions involved
      in airway inflammation.

PMID- 15454121
TI  - Para-Bromophenacyl bromide alleviates airway hyperresponsiveness and modulates
      cytokines, IgE and eosinophil levels in ovalbumin-sensitized and -challenged
      mice.
AB  - Airway hyperresponsiveness, airway eosinophilia and increased IgE levels in serum
      are the important characteristic features of asthma. We evaluated the potential
      of para-Bromophenacyl bromide (PBPB), a known phospholipase A(2) inhibitor, on
      allergen-induced airway hyperresponsiveness in a mouse model. We sensitized and
      challenged mice with ovalbumin (OVA) to develop airway hyperresponsiveness as
      assessed by airway constriction and airway hyperreactivity (AHR) to methacholine
      (MCh) induced by allergen. The mice were orally treated with PBPB (0.1, 1 and 10
      mg/kg) during or after OVA-sensitization and OVA-challenge to evaluate its
      protective or reversal effect on airway constriction and AHR to MCh.
      Determination of OVA-induced airway constriction and AHR to MCh were performed by
      measuring specific airway conductance (SGaw) using non-invasive dual-chamber
      whole body-plethysmography. We observed that PBPB (1 mg/kg) significantly reduced
      OVA-induced airway constriction and AHR to MCh (p<0.01). PBPB (1 mg/kg) treatment
      significantly inhibited PLA(2) activity in the BAL fluid. Cytokine analysis of
      the BAL fluid revealed that PBPB caused an increase in interferon-gamma (IFN
      gamma) (p<0.02) and a decrease in interleukin-4 (IL-4) (p<0.05) and interleukin-5
      (IL-5) (p<0.05) levels. The OVA-specific serum IgE levels (p<0.01) and the BAL
      eosinophils (p<0.001) were also reduced significantly. Thus, PBPB is capable of
      modulating allergen induced cytokine levels and serum IgE levels, and alleviating
      allergen induced airway hyperresponsiveness and eosinophils in mice. These data
      suggest that PBPB could be useful in the development of novel agents for the
      treatment of allergen induced airway hyperresponsiveness.

PMID- 15454122
TI  - Haemato-biochemical and immuno-pathophysiological effects of chronic toxicity
      with synthetic pyrethroid, organophosphate and chlorinated pesticides in broiler
      chicks.
AB  - Haemato- biochemical and immuno-pathophysiological changes following feeding of
      broiler chicks with 20 ppm fenvalerate (synthetic pyrethroid, SP), 2 ppm
      monocrotophos (organophosphate, OP) and 2 ppm endosulfan (chlorinated
      hydrocarbon, CH) were studied. Four groups of broiler birds (30 each) were fed
      poultry mash without (control) or mixed with pesticides for 8 weeks. Blood
      glucose, serum globulin and acetyl cholinesterase (AChE) activity level were
      decreased (P<0.01) in all treated groups compared to control, but not the serum
      albumin and BUN. The total ATPase activity was enhanced (P<0.01) in fenvalerate
      and monocrotophos than birds in control group. Body weight, total erythrocyte
      count, packed cell volume, haemoglobin, eosinophil and monocyte count did not
      show any changes. Total leucocytes and T-lymphocyte count was lower (P<0.01) in
      all treated groups as compared to control group. B-cell count (P<0.01), mean 2-4
      dinitrofluorobenzene (DNFB) dermal sensitivity score and splenic indices from
      graft vs. host reaction (P<0.05) were decreased in fenvalarate and endosulfan but
      the values for monocrotophos were intermediate between control and other treated
      groups. Pesticide intoxication reduced nitroblue tetrazolium (NBT) positive cells
      (active splenic macrophages) (P<0.05) and spleen weight (P<0.01). Whereas bursal
      weight was reduced only with endosulfan, thymic weight was reduced on endosulfan
      and fenvalerate-treated feed. Microscopic examination of these organs further
      revealed atrophy/hypoplasia, decrease in the size of follicles with depletion of
      lymphocytes and haemorrhages in thymus. The study concludes that the chronic
      exposure of chicks to small amount of SP, OP and CH pesticide leads to
      deleterious effects on metabolism and immune system of birds.

PMID- 15454123
TI  - Felty's syndrome.
AB  - Felty's syndrome (FS) comprises a triad of rheumatoid arthritis (RA), neutropenia
      and splenomegaly, occurring in less than 1% of RA patients. Clinically it is
      characterized by severe joint destruction contrasting with moderate or absent
      joint inflammation and severe extra-articular disease, including a high frequency
      of rheumatoid nodules, lymphadenopathy, hepatopathy, vasculitis, leg ulcers, skin
      pigmentation etc. Recurrent bacterial infections are mostly due to the severe,
      otherwise unexplained neutropenia. The cause of neutropenia lies in both
      decreased granulopoiesis and increased peripheral destruction of granulocytes.
      Recurrent infections may lead to increased mortality. Spontaneous remission of
      the syndrome also occurs. Over 95% of FS patients are positive for rheumatoid
      factor (RF), 47-100% are positive for antinuclear antibody (ANA), and 78% of
      patients have the HLA-DR4*0401 antigen. Some 30% of FS patients have large
      granular lymphocyte (LGL) expansion. LGL expansion associated with uncomplicated
      RA is immunogenetically and phenotypically very similar to but clinically
      different from FS. Neutropenia of FS can be effectively treated with disease
      modifying anti-rheumatic drugs (DMARDs), the widest experience being with
      methotrexate (MTX). Results of treatment with granulocyte colony-stimulating
      factor (G-CSF) are encouraging, but there is no experience with other biological
      agents. Splenectomy results in immediate improvement of neutropenia in 80% of the
      patients, but the rate of infection decreases to a lesser degree.

PMID- 15454124
TI  - Palindromic rheumatism and other relapsing arthritis.
AB  - Patients with recurrent or relapsing arthritis are frequently seen in
      rheumatological practice. Besides crystal arthritis, the most frequent cause of
      recurrent arthritis, there are several diseases that may present clinically as
      intermittent mono- or polyarthritis. Palindromic rheumatism is the paradigm of
      this type of condition, but other diseases such as systemic autoinflammatory
      disorders (periodic fever syndromes), Whipple's disease, arthritis associated
      with hyperlipidemia, intermittent hydrarthrosis and other diseases should be
      taken into account in the differential diagnosis of patients with recurrent
      arthritis. In this chapter, we discuss recent developments in these diseases with
      special emphasis on palindromic rheumatism, a common condition whose close
      relationship with rheumatoid arthritis remains intriguing.

PMID- 15454125
TI  - Adult-onset Still's disease.
AB  - Adult-onset Still's disease (AOSD) is a systemic inflammatory disorder of unknown
      etiology and pathogenesis. AOSD is a rare condition, usually presenting with high
      fever accompanied by systemic manifestations. The disease is a heterogeneous
      pathological entity with a range of etiologies, manifestations and prognosis.
      There is no single diagnostic test for AOSD; rather, the diagnosis is based upon
      clinical criteria such as arthralgia, fever, skin rash, lymphadenopathy, and
      hepatosplenomegaly. Determination of the procalcitonin level and the biological
      response to empirical corticosteroid therapy generally helps the diagnosis, while
      immune-serology, as a 'screening' test, will not add meaningful information in
      most cases. Treatment consists of anti-inflammatory medications. Non-steroid anti
      inflammatory drugs have limited efficacy, corticosteroid therapy and disease
      modifying antirheumatic drugs are usually required. Novel therapeutic approaches,
      such as anti-tumor necrosis factor blockade and stem cell transplantation, are
      promising. In this chapter we present clinical and laboratory parameters of 18
      patients diagnosed with AOSD at our institution between 1997 and 2003, and review
      the literature.

PMID- 15454126
TI  - Drug-induced autoimmunity.
AB  - Drug induced autoimmune syndromes have been recognized for many years. The
      classical presentation is that of drug-induced lupus, a generally milder version
      of the idiopathic disorder that is associated with production of antihistone
      antibodies. This pattern is now changing, in part due to the many new drugs that
      have been introduced into clinical practice for treatment of autoimmune diseases,
      including both conventional pharmaceuticals and biologicals. The number and
      complexity of drug-induced autoimmune syndromes has increased, and many are now
      associated with autoantibodies that have been classically defined as limited to
      idiopathic disease states. Furthermore, some of these drug-induced syndromes have
      life-threatening complications, so that recognition of drug-induced disease has
      become more difficult at a time when it is more urgent to establish a correct
      diagnosis. Many reports are limited to case descriptions, and few controlled
      investigations have been carried out. Nevertheless, it is possible to derive an
      approach to considering possible mechanisms by which these processes may take
      place. This chapter will consider these proposed mechanisms, using some of the
      implicated drugs to illustrate possible pathogenetic pathways.

PMID- 15454127
TI  - Reactive arthritis.
AB  - Reactive arthritis is an infectious disease which may be initiated by several
      microbes in genetically susceptible hosts. The best known predisposing genetic
      factor is HLA-B27, but the mechanisms behind its action are still elusive.
      Worldwide agreement exists regarding the general guidelines in the diagnosis,
      differential diagnosis and management, even though official diagnostic criteria
      are not yet available. Several studies indicate that antibiotics are effective
      only if started before the immunological mechanisms of pathogenesis have been
      turned on. However, recent observations suggest that a 3-month course of
      antibiotics may diminish the late risk of chronic sequelae, especially in HLA-B27
      positive patients with reactive arthritis.

PMID- 15454128
TI  - Polymyalgia rheumatica.
AB  - Polymyalgia rheumatica (PMR) is an inflammatory condition of unknown etiology
      characterized by aching and stiffness in the shoulder and in the pelvic girdles
      and neck. In the past, PMR was considered a manifestation of giant cell arteritis
      (GCA) or a variant of elderly-onset rheumatoid arthritis (EORA). The current
      diagnostic criteria for PMR were empirically formulated by clinical experts who
      had studied the disease extensively. Arthroscopic, radioisotopic and magnetic
      resonance imaging studies all have indicated the presence of a synovitis in
      proximal joints and periarticular structures. The synovitis is probably
      responsible for the musculoskeletal symptoms in PMR. The prominence assigned to
      the proximal symptoms has probably overshadowed the less well recognized and more
      variable distal musculoskeletal manifestations which are present in about half of
      the cases. A normal erythrocyte sedimentation rate does not exclude a diagnosis
      of PMR. C-reactive protein and interleukin-6 seem to be more sensitive indicators
      of disease activity both at diagnosis and during relapse/recurrence.
      Corticosteroids are the drugs of choice for treating PMR. A course of treatment
      of 1-2 years is often required. However, some patients have a chronic, relapsing
      course and require low doses of corticosteroids for several years. Large,
      multicenter, double-blind, placebo-controlled studies are required to define the
      role of methotrexate and anti-TNF-alpha agents as corticosteroid-sparing drugs in
      PMR.

PMID- 15454129
TI  - Relapsing polychondritis.
AB  - Relapsing polychondritis (RP) is a rare multisystem autoimmune disease of unknown
      origin characterized by recurrent episodes of inflammation and progressive
      destruction of cartilaginous tissues. Elastic cartilage of the ears and nose,
      hyaline cartilage of peripheral joints, vertebral fibrocartilage and
      tracheobronchial cartilage, as well as proteoglycan-rich structures of the eye,
      heart, blood vessels or inner ear may all be affected. In most patients RP
      manifests in a fluctuating but progressive course which eventually results in a
      significant shortening of life expectancy. The relatively uncommon occurrence,
      the unknown etiopathogenesis, the ambiguous clinical pattern, as well as the
      variety in its course and response to therapy may all contribute to the
      difficulties the physician must overcome when managing RP. Beside describing the
      main features of RP and seven clinical cases of our own, in the present review we
      focus on recent findings in the etiopathogenesis and novel treatment options.

PMID- 15454130
TI  - Erosive osteoarthritis.
AB  - Erosive osteoarthritis (EOA) is believed to be a clinically uncommon subset of
      generalized osteoarthritis (OA) characterized by a clinical course, which is
      frequently aggressive. The diagnosis of EOA is accepted only for patients meeting
      American College of Rheumatology clinical criteria for OA of the hand and showing
      radiographic aspects of articular surface erosions. Conditions to be considered
      in the differential diagnosis include primarily nodal generalized OA, psoriatic
      arthritis and rheumatoid arthritis. It is possible to find erosive changes
      resembling EOA in endocrine diseases, microcrystal-induced diseases, chronic
      renal diseases, autoimmune diseases and others. Despite the absence of a clear
      etiology, immunogenetic studies are useful in identifying a possible
      predisposition to developing EOA in some subjects. No definitive therapeutic
      approach to EOA has been reported. It is reasonable to assume that in the
      presence of a symptomatic EOA our therapeutic approach should differ from that
      used for common, nodal, non-EOA.

PMID- 15454131
TI  - Multicentric reticulohistiocytosis.
AB  - Multicentric reticulohistiocytosis (MR) is an uncommon disease with joint and
      cutaneous manifestations most commonly affecting women in middle age. The
      diagnosis must be confirmed by the histological evidence of typical mononuclear
      histiocytes and multinucleated giant cells. Many conditions have been described
      in association with MR, and the clinician should be aware that in many cases the
      disease is associated with malignancy. This eventuality must be accurately ruled
      out. If the typical nodular manifestations are missing at the onset, the
      arthritic complaints-usually localized but not confined to the interphalangeal
      joints-may be confused with those of more common rheumatic disorders. At this
      stage, a careful clinical and radiological evaluation may offer the key to the
      correct diagnosis. The natural course of the disease may develop into a severe,
      destructive arthropathy and disfiguring cutaneous lesions. In these cases an
      aggressive treatment with immunosuppressive drugs is strongly recommended. On the
      basis of recent reports, anti-tumor necrosis factor alpha agents and alendronate
      may also be added to the list of the drugs used in the treatment of this disease.

PMID- 15454133
TI  - Telerounding and patient satisfaction after surgery.
AB  - BACKGROUND: Technologic advances in communications have facilitated the
      development and diffusion of telemedicine. Most applications have focused on
      remote outpatient management of medical conditions. We assessed the impact of
      introducing remote video conferencing during the immediate postoperative period
      (telerounds) on patient-reported satisfaction with their hospitalization. STUDY
      DESIGN: Between October 2002 and June 2003,85 patients undergoing elective
      laparoscopic or percutaneous urologic procedures were enrolled in a trial testing
      the impact of telerounds on patients' satisfaction with their hospitalization.
      Participants were entered into one of three postoperative care arms: standard
      once-daily attending bedside rounds; standard once-daily attending level bedside
      rounds plus one afternoon telerounding visit; or a substitution of one daily
      bedside round with a robotic telerounding visit. Participants completed a
      validated patient satisfaction survey 2 weeks after hospital discharge. RESULTS:
      Eighty-five individuals (100% response rate) completed the questionnaire. With
      responses dichotomized to "excellent" or "other," patients in the telerounding
      arm demonstrated statistically substantial improvements in ratings of examination
      thoroughness, quality of discussions about medical information, postoperative
      care coordination, and attending physician availability. Patients in the robotic
      telerounding arm indicated considerably higher satisfaction with regard to
      physician availability. After adjusting for age differences, ratings of each of
      the previously listed aspects of care remained notably improved in the
      telerounding arm. CONCLUSIONS: Telerounding either as an additional visit or as a
      substituted bedside visit is associated with increased patient satisfaction in
      postoperative care. This type of interaction appears to acceptably facilitate
      physician communication with hospitalized patients.

PMID- 15454134
TI  - Hospital costs associated with surgical complications: a report from the private
      sector National Surgical Quality Improvement Program.
AB  - BACKGROUND: The National Surgical Quality Improvement Project (NSQIP) has reduced
      morbidity rates in Veterans Affairs Hospitals. As the NSQIP methods move to
      private-sector hospitals, funding responsibilities will shift to the medical
      center. The objective of the current study was to calculate hospital costs
      associated with postoperative complications, because reducing morbidity may
      offset the costs of using the NSQIP. STUDY DESIGN: Patient data were obtained
      from a single private-sector center involved in the NSQIP from 2001 to 2002
      (n=1,008). Cost data were derived from the hospital's internal cost-accounting
      database (TSI; Transitions Systems Inc). Total hospital costs associated with
      both minor complications and major complications were calculated. Multiple linear
      regression was used to determine the cost of each type of complication after
      adjusting for patient characteristics. RESULTS: Rates of minor complications
      (6.3%, 64 events) and major complications (6.6%, 67 events) were similar. Median
      hospital costs were lowest for patients without complications (4,487 dollars)
      compared with those with minor (14,094 dollars) and major complications (28,356
      dollars) (p<0.001). After adjusting for differences in patient characteristics,
      major complications were associated with an increase of 11,626 dollars (95% CI,
      9,419 dollars to 13,832 dollars; p<0.001). Minor complications were not
      associated with increased costs in the adjusted analysis. CONCLUSIONS: Given the
      substantial costs associated with major postoperative complications, reducing
      morbidity may provide sufficient cost savings to offset the resources needed to
      participate in the private-sector expansion of the NSQIP.

PMID- 15454135
TI  - Liver cirrhosis in patients undergoing laparotomy for trauma: effect on outcomes.
AB  - BACKGROUND: There is little published work on the effect of cirrhosis on outcomes
      in trauma patients undergoing laparotomy. The aim of this study was to evaluate
      the risk of death or serious complications in cirrhotic trauma patients
      undergoing laparotomy as compared with that in a similar group of patients
      without cirrhosis. STUDY DESIGN: During a 12-year period, there were 46 patients
      with the diagnosis of liver cirrhosis made during laparotomy for trauma. Each
      patient was matched with two noncirrhotic controls on the basis of 7 criteria:
      age (>55, </=55 years), gender, mechanism of injury (blunt, penetrating), Injury
      Severity Score (</=15, 16-25, >25), head Abbreviated Injury Score (<3, >/=3),
      chest Abbreviated Injury Score (<3, >/=3), and abdominal Abbreviated Injury Score
      (<3, >/=3). Six cirrhotic patients were excluded because matching was not
      possible. The remaining 40 patients were matched with 80 noncirrhotic control
      patients selected from a pool of 4,771 patients who had trauma laparotomies.
      Outcomes included mortality, ARDS, pneumonia, renal failure, abdominal sepsis,
      disseminated intravascular coagulopathy, ICU and hospital stay, and hospital
      charges. Outcomes between the two study groups were compared with conditional
      logistic analysis. Hazard ratio (95% CI) and adjusted p value with the stepdown
      Bonferroni method were derived. RESULTS: The overall mortality in the cirrhotic
      group was significantly higher than that in the matched noncirrhotic group (45%
      versus 24%, hazard ratio: 7.60 [2.00, 28.94], p = 0.021). Mortality in patients
      with Injury Severity Score </=15 was 29% in the cirrhotic group and 5% in the
      noncirrhotic group (p = 0.013) and in patients with Injury Severity Score 16-25,
      mortality was 56% and 11%, respectively (p = 0.024). The incidence of any of the
      predetermined complications was 45% in the cirrhotic group and 23% in the
      noncirrhotic group (p = 0.110). The mean surgical ICU stay was 11.5 days and 6.6
      days, respectively (p = 0.037), and the mean hospital charges were $141,210 and
      $72,884, respectively (p = 0.031). CONCLUSIONS: Cirrhotic trauma patients
      undergoing laparotomy are at high risk of serious complications and death, even
      after fairly minor injuries. This group of patients should be admitted to the ICU
      for close monitoring and aggressive management irrespective of the severity of
      injuries.

PMID- 15454136
TI  - Impact of gastric bypass operation on survival: a population-based analysis.
AB  - BACKGROUND: Bariatric procedures are increasingly performed but their impact on
      survival is unknown. STUDY DESIGN: We evaluated short- and longterm mortality
      rates of patients undergoing gastric bypass on a population level compared with a
      nonoperated cohort of patients with morbid obesity in a retrospective study,
      using the Washington State Comprehensive Hospital Abstract Reporting System
      database and the Vital Statistics database. The study included all patients (age
      18 to 65 years) from 1987 to 2001 who underwent gastric bypass with ICD-9
      diagnostic codes for obesity. The comparator group included patients of similar
      age with a diagnosis of obesity or morbid obesity who did not have a bariatric
      procedure. Survival analysis was used to determine the association of surgeon
      experience on 30-day mortality and of the procedure on survival while controlling
      for age, gender, and comorbidity index. RESULTS: Of the 66,109 obese patients we
      evaluated, 3,328 had a bariatric procedure. Incidence of the procedure increased
      from 0.7 to 10.6 per 100,000 from 1987 to 2001, with a 2.5-fold increase in
      incidence rate of the procedure in the years after 1996 (incidence rate ratio,
      2.5; 95% CI, 2.4 to 2.7). Thirty-day mortality was 1.9% and was associated with
      surgical inexperience. Within the surgeon's first 19 procedures the odds of death
      within 30 days were 4.7 times higher (95% CI, 1.2 to 18.2) than at later points
      in a surgeon's case order. At 15 years followup, 16.3% of nonoperated patients
      had died as compared with 11.8% of patients who had the bariatric procedure. When
      survival was compared beginning 1 year after the procedure, the adjusted hazard
      for death was 33% lower than that of nonoperated patients (hazard ratio 0.67; 95%
      CI, 0.54 to 0.85). CONCLUSIONS: Thirty-day mortality after gastric bypass is
      higher than previously reported and closely linked to surgeon inexperience. A
      modest overall survival benefit was associated with the procedure but a marked
      survival advantage was noted for patients who survive to the first postoperative
      year.

PMID- 15454137
TI  - Gastric carcinoids in patients with hypergastrinemia.
AB  - BACKGROUND: Hypergastrinemia in patients with pernicious anemia is a major
      regulator contributing to enterochromaffin-cell hyperplasia and, ultimately, to
      gastric carcinoids. STUDY DESIGN: Between 1990 and 2003, we studied 8 women and
      10 men with pernicious anemia and gastric carcinoids; their mean age was 50
      years. Serum gastrin levels ranged from 740 to 4,000 pg/mL (mean 1,000 pg/mL).
      Six patients underwent antrectomy, four total gastrectomy, and eight endoscopic
      resection or biopsy. During the same period, 22 patients with Zollinger-Ellison
      tumors and hypergastrinemia (20 men and 2 women, mean age 49 years) had no
      gastric carcinoids, but 1 of 7 patients with Zollinger-Ellison and multiple
      endocrine neoplasia (MEN1) tumors had hypergastrinemia and gastric carcinoids.
      RESULTS: Mean followup for pernicious anemia patients was 6 years after
      antrectomy and 1 to 10 years after endoscopic resection or biopsy. Tumor
      regression was observed in one patient after antrectomy and one patient after
      biopsy. There were no deaths in this group in spite of lymph node metastasis in
      two patients. The patient with Zollinger-Ellison and MEN1 syndrome has been
      followed 3 years after diagnosis and 2 years after total gastrectomy.
      CONCLUSIONS: Gastric carcinoids are indolent tumors occurring with increasing
      frequency in patients with pernicious anemia. Antrectomy or biopsy and
      observation are preferred methods of treatment. Total gastrectomy is reserved for
      patients with extensive tumor involvement of the gastric wall or for emergency
      bleeding.

PMID- 15454138
TI  - Voice changes after thyroidectomy without recurrent laryngeal nerve injury.
AB  - BACKGROUND: Injury of the inferior laryngeal nerve is not the only cause of voice
      alteration after thyroidectomy; many patients notice minimal changes immediately
      after operation, without evidence of inferior laryngeal nerve damage. We
      hypothesized that there may be other causes for voice modification, such as
      injuries of the superior laryngeal nerve, prethyroid strap muscles, and
      cricothyroid muscles. We describe voice changes after total thyroidectomy,
      without inferior laryngeal nerve injury, using a computer program to objectively
      compare different patterns of voice. STUDY DESIGN: Forty-six consecutive patients
      who underwent total thyroidectomy were studied between March 1997 and December
      1999. Acoustic voice analysis was performed preoperatively and at the second,
      fourth, and sixth postoperative months using a microphone adapted to a personal
      computer. Parameters measured were intensity of the voice (Shimmer) and
      fundamental frequency (Fo). RESULTS: No complications occurred during operation
      or in the postoperative period. Voice fatigue during phonation was the most
      common symptom after thyroidectomy. Forty patients (87%) stated that their voices
      had changed since the operation, and common complaints were voice alteration
      while speaking loudly, changes in voice pitch, and voice disorder while singing.
      Changes in the Fo and Shimmer values in smokers versus nonsmokers were similar
      (Fo overall, p = 0.56; Shimmer overall, p = 0.66), as were the same parameters in
      benign and malignant pathologies (Fo overall, p = 0.66; Shimmer overall, p =
      0.67). CONCLUSIONS: Voice changes after uncomplicated thyroidectomy occur and can
      be objectively measured. This is important in the preoperative counseling of
      patients before thyroidectomy, for ethical and legal purposes.

PMID- 15454139
TI  - Intradermal radioisotope is superior to peritumoral blue dye or radioisotope in
      identifying breast cancer sentinel nodes.
AB  - BACKGROUND: Sentinel lymph node (SLN) mapping and biopsy have emerged as the
      technique of choice for axillary staging of breast cancer. Several methods have
      been developed to identify SLNs, including peritumoral or intradermal injection
      of isosulfan blue dye or technetium sulfur colloid (TSC). We hypothesize that
      intradermal TSC is the optimal mapping technique and can be used alone to
      identify SLNs. STUDY DESIGN: From March 1997 through January 2001, 180 women with
      T1 and T2 invasive breast cancer and clinically negative axilla underwent SLN
      mapping and biopsy. Peritumoral TSC was injected in 74 patients, 62 of whom also
      received peritumoral blue dye. Intradermal TSC (above tumor) was performed in 94
      patients, 76 of whom also received peritumoral blue dye. Technetium-rich nodes
      were identified intraoperatively using a hand-held gamma probe and blue nodes
      were identified visually. Hematoxylin- and eosin-stained SLN sections were
      examined by light microscopy for breast cancer metastases. RESULTS: Overall, the
      SLN mapping procedures were successful in 91% of patients. Peritumoral and
      intradermal TSC were successful in identifying SLNs in 78% and 97% of patients,
      respectively. Peritumorally injected isosulfan blue was successful in identifying
      83% of SLNs. Intradermal TSC was found to be superior to peritumoral TSC and
      peritumoral blue dye in identifying SLNs (p = 0.00094, chi-squared, and p =
      0.020, ANOVA). CONCLUSIONS: SLN mapping by intradermal TSC has a significantly
      higher success rate than peritumoral TSC or blue dye. There was minimal benefit
      in identifying additional SLNs with addition of peritumoral blue dye to
      intradermal TSC. So, SLN mapping and biopsy using intradermal-injected TSC can be
      used alone to effectively stage the axilla for breast cancer.

PMID- 15454140
TI  - Insurance status and race represent independent predictors of undergoing
      laparoscopic surgery for appendicitis: secondary data analysis of 145,546
      patients.
AB  - BACKGROUND: Studies have shown that racial and socioeconomic differences lead to
      inequality in access to health care. It is unknown whether insurance status and
      race affect the choice of surgical treatment for patients presenting with
      appendicitis. STUDY DESIGN: Patients with primary ICD-9 procedure codes for
      laparoscopic and open appendectomy were selected from the 1998, 1999, and 2000
      Nationwide (US) Inpatient Samples. The primary predictor variables were insurance
      status (private, Medicare, Medicaid, other) and race (Caucasian, African
      American, Hispanic, other). Multiple logistic regression models were used to
      assess whether insurance status and race are associated with the choice of
      surgical procedure for patients presenting with appendicitis. RESULTS: Discharge
      abstracts of 145,546 patients were used for our analyses. There were 32,407
      patients (22.3%) who underwent laparoscopic appendectomy and 113,139 patients
      (77.7%) who had open appendectomy. Although 24.2% of privately insured patients
      underwent laparoscopic appendectomy, only 16.9% of Medicare patients, 17.4% of
      Medicaid patients, and 19.6% of patients in the "other" insurance category were
      treated using the laparoscopic procedure (p < 0.001). Caucasian patients
      underwent laparoscopic surgery in 24.8%, African Americans in 18.6%, Hispanics in
      19.6%, and other ethnicities in 18.8% of patients (p < 0.001). Compared with the
      Medicaid subset, and after adjusting for potential confounders such as age,
      gender, race, patient comorbidity, median ZIP code income, hospital location and
      teaching status, and presence of abscess or perforation, privately insured
      patients (odds ratio [OR] = 1.26, 95% [CI [1.20, 1.33], p < 0.001) and Medicare
      patients (OR = 1.17, 95% CI [1.05, 1.30], p = 0.004) were significantly more
      likely to undergo laparoscopic surgery. Caucasian patients (OR = 1.42, 95% CI
      [1.33, 1.51], p < 0.001) and Hispanics (OR = 1.12, 95% CI [1.04, 1.20], p =
      0.002) were significantly more likely to have laparoscopic appendectomy, compared
      with African Americans, even after adjusting for the previously mentioned
      confounders and insurance status. CONCLUSIONS: Even after adjusting for potential
      confounders, insurance status and race are marked independent predictors of
      having laparoscopic surgery in patients treated for appendicitis in this sample.

PMID- 15454143
TI  - The future of wound healing: pursuing surgical models in transgenic and knockout
      mice.
AB  - BACKGROUND: Transgenic and knockout technologies have made determination of the
      molecular basis of wound healing possible. But there is no comprehensive or
      standardized approach to the investigation of wound healing in the mouse. A
      convention is proposed for assessing the multiple dimensions of wound healing. An
      approach to phenotyping a transgenic or knockout animal in a reproducible fashion
      is presented using this convention. STUDY DESIGN: Age- and gender-matched
      wildtype and knockout mice were characterized using six parameters of wound
      healing: epithelialization, granulation tissue formation, contraction, tensile
      strength, angiogenesis, and response to ischemia. Six surgical (four standard and
      two impaired) models were designed and used to quantitate these parameters. These
      models can be combined to efficiently maximize the data from any given subject.
      RESULTS: Each model leads to a rapid yield of results, with an average turnover
      of 4.9 days (range 3 to 7 days), and morbidity and mortality were minimal. A
      combinatorial approach elucidates the precise wound repair deficit of any
      subject. A case example is presented. CONCLUSIONS: Six surgical models
      investigating pertinent wound healing parameters are available. A factorial
      approach of quantitative wound healing assays maximizes data gathered from any
      one animal, minimizing the number of transgenic and knockout subjects needed;
      finely dissects molecular pathways of wound healing; and rapidly phenotypes a
      particular genetically altered mouse. We propose a standardized approach to wound
      healing assays that will elucidate critical cellular and molecular mechanisms and
      potential therapies.

PMID- 15454144
TI  - The preischemic combination of the sodium-hydrogen exchanger inhibitor cariporide
      and the adenosine agonist AMP579 acts additively to reduce porcine myocardial
      infarct size.
AB  - BACKGROUND: We tested whether the combination of two known cardioprotective
      agents, the type-1 sodium-hydrogen exchanger inhibitor cariporide plus the
      adenosine A(1)/A(2a) receptor agonist AMP579 ([1S-[1a,2b,3b, 4a(S*)]]-4-[7-[[2-(3
      chloro-2-thienyl)-1-methylpropyl]amino]-[(3)H]-imidazo[4,5-b]pyridyl-3
      yl]cyclopentane carboxamide), acted additively to reduce myocardial infarct size.
      STUDY DESIGN: Pigs underwent 1 hour of coronary artery occlusion and 3 hours
      reperfusion. Vehicle-treated controls were compared with animals treated before
      ischemia with low-dose and high-dose cariporide and AMP579, and low-dose
      cariporide plus AMP579. The effects of both agents, alone and in combination,
      were also tested in isolated porcine polymorphonuclear neutrophils (PMNs). The
      PMN respiratory burst was induced with phorbol 12-myristate 13-acetate and
      quantified by the increase in 2',7'-dichlorofluorescein fluorescence, measured by
      flow cytometry. RESULTS: Infarct size in the control pigs was 65 +/- 1% of the
      area at risk. Cariporide dose-dependently reduced infarct size to 39 +/- 2% and
      24 +/- 3% in the low- and high-dose groups, respectively. Infarct size was 54 +/-
      3% in the low-dose AMP579 group and 47 +/- 3% with high dose. The combination of
      low doses of cariporide and AMP579 reduced infarction to 25 +/- 6% of the area at
      risk. In the PMN studies, cariporide and AMP579 alone had no effect on 2',7'
      dichlorofluorescein fluorescence, but the combination of the two agents reduced
      the PMN 2',7'-dichlorofluorescein increase to 79 +/- 5% of the vehicle control
      response. CONCLUSIONS: The preischemic combination of low doses of cariporide and
      AMP579 decreased myocardial infarct size more than either agent used alone in low
      concentration, indicating an additive effect of the two agents. Given the effects
      that cariporide plus AMP579 combination exerted on PMN activity, it appears that
      this combination has the potential to reduce PMN-mediated effects during
      myocardial reperfusion.

PMID- 15454145
TI  - Endotoxin reduces CD95-induced neutrophil apoptosis by cIAP-2-mediated caspase-3
      degradation.
AB  - BACKGROUND: Reduced apoptosis of neutrophil granulocytes (PMN) contributes to
      pathogenesis of systemic inflammatory response syndrome, sepsis, and multiple
      organ dysfunction syndrome. The intracellular inhibitor of apoptosis proteins has
      been shown to inhibit activated caspase-3. We investigated the turnover dynamics
      of cIAP-2 mRNA and caspase-3 protein in a neutrophil ex vivo model of sepsis.
      STUDY DESIGN: PMN (1 x 10(6)/mL) from 7 healthy volunteers were preincubated with
      endotoxin (lipopolysaccharide [LPS], 1 microg/mL) for 5 hours, followed by an
      additional hour with or without the proteasome inhibitor (30 microM), before
      incubation with or without agonistic CD95 antibody (100 ng/mL) for another 16
      hours. Apoptosis was quantified by Annexin-V and propidium iodide staining by
      flow cytometry (using a fluorescence-activated cell sorter). Caspase-3 activity
      was determined by DEVD-afc-cleavage assay. Expression of ubiquitinated caspase-3
      and cIAP-2 protein was detected by Western blot analysis and cIAP-2 mRNA by
      reverse transcriptase-polymerase chain reaction. RESULTS: Within 2 hours LPS
      induced cIAP-2 mRNA and protein. In addition, LPS increased ubiquitination of
      activated caspase-3. LPS significantly (p < 0.05) reduced spontaneous (66.1 +/-
      2.3% to 24.8 +/- 4.8%) and CD95-induced (90.8 +/- 0.9% to 64.3 +/- 4.2%)
      apoptosis and caspase-3 activation. Inhibition of the proteasome completely
      abolished the antiapoptotic effect of LPS on spontaneous (52.6 +/- 2.4%) and CD95
      induced (88.7 +/- 2.6%) apoptosis and degradation of caspase-3. CONCLUSIONS:
      Induction of cIAP-2 by endotoxins and accelerated degradation of activated
      caspase-3 by the proteasome might be responsible for reduced apoptosis in PMN
      during sepsis.

PMID- 15454146
TI  - Comparison of bench test evaluations of surgical skill with live operating
      performance assessments.
AB  - BACKGROUND: Attempts at assessing surgical proficiency have generally used
      laboratory simulation to evaluate skill. The aim of this study was to compare
      technical ability as measured on a bench simulation with actual operative
      performance. STUDY DESIGN: Twenty-two general surgeons and trainees were
      recruited: consultants (n = 4), specialist registrars (n = 14), and senior house
      officers (n = 4). They were assessed while performing a saphenofemoral dissection
      on an anesthetized patient in the operating theater, and performing the same
      procedure on an inanimate model within the laboratory. The Objective Structured
      Assessment of Technical Skill method, consisting of a 7-parameter global rating
      (maximum score 35) and 17-point step-by-step checklist (maximum score 17) was
      used to measure performance in both environments. Face, content, and construct
      validity of the synthetic model were established as part of this study. RESULTS:
      There was a significant relationship between technical skill as measured on the
      bench test model and performance within the operating theater with respect to
      both global rating (Spearman correlation coefficient 0.824, p < 0.001; alpha
      coefficient 0.89) and checklist ratings (r = 0.514, p < 0.02; alpha coefficient
      0.68) rating assessments. Global rating scores correlated with experience for
      both operative (r = 0.822, p < 0.001) and bench (r = 0.515, p < 0.05) settings.
      There was no difference in level of measured performance between operating
      theater and bench model (global rating mean 23.25 +/- 6.66 versus 23.75 +/- 5.62,
      respectively; paired t-test p = 0.559). CONCLUSIONS: Assessment of technical
      skill using inanimate procedural simulation translates to actual surgical
      performance within the operating theater. This further validates use of bench
      test evaluations to measure surgical technical ability.

PMID- 15454147
TI  - Sildenafil citrate alleviates pulmonary hypertension after hypoxia and
      reoxygenation with cardiopulmonary bypass.
AB  - BACKGROUND: Sudden reoxygenation of hypoxic neonates undergoing cardiac operation
      exacerbates the systemic inflammatory response to cardiopulmonary bypass
      secondary to reoxygenation injury, worsening cardiopulmonary dysfunction. Reports
      suggest sildenafil decreases pulmonary hypertension and may affect myocardial
      function. Sildenafil's efficacy for treating postbypass cardiopulmonary
      dysfunction remains unknown. STUDY DESIGN: Fourteen neonatal piglets (5 to 7 kg)
      underwent 90 minutes of hypoxia, 60 minutes of reoxygenation with cardiopulmonary
      bypass, and 120 minutes of recovery. Six animals received 50 mg oral sildenafil
      and eight received saline at hypoxia. Data are presented as mean +/- SD. RESULTS:
      Sildenafil prevented the high pulmonary vascular resistance observed in controls
      (controls baseline 81 +/- 37 dynes. s/cm(5) versus recovery 230 +/- 93 dynes.
      s/cm(5), p = 0.004; sildenafil baseline 38 +/- 17 dynes. s/cm(5) versus recovery
      101 +/- 60 dynes. s/cm(5), p = 0.003). Despite lower pulmonary vascular
      resistance after sildenafil, arterial endothelin-1 (ET-1) was increased in both
      groups (control baseline 1.3 +/- 0.5 pg/mL versus recovery 4.5 +/- 3.7 pg/mL, p =
      0.01; sildenafil baseline 1.3 +/- 0.3 pg/mL versus recovery 9.8 +/- 4.9 pg/mL, p
      = 0.003). Intravenous nitric oxide (NO) levels were preserved after sildenafil
      treatment (sildenafil baseline 340 +/- 77 nM versus recovery 394 +/- 85 nM). IV
      NO levels in controls were decreased when compared with baseline (control
      baseline 364 +/- 83 nM versus recovery 257 +/- 97 nM, p = 0.028). Although levels
      of exhaled NO decreased in both groups, the sildenafil-treated animals had higher
      levels of exhaled NO when compared with controls at the end of recovery (0.6 +/-
      0.4 parts per billion versus 1.8 +/- 0.9 parts per billion, respectively, p =
      0.029). CONCLUSIONS: Sildenafil alleviated pulmonary hypertension after
      reoxygenation with cardiopulmonary bypass. Despite increased ET-1 levels,
      pulmonary vascular resistance was lower with sildenafil treatment, suggesting
      sildenafil's effect on the pulmonary vasculature is capable of countering
      vasoconstriction by ET-1. Further study into the role of sildenafil in
      perioperative therapy and its interactions with ET-1 are warranted.

PMID- 15454148
TI  - Impact of mandatory resident work hour limitations on medical students' interest
      in surgery.
AB  - BACKGROUND: The number of US medical students applying for general surgery
      residency has been declining. Recent studies have shown that the issue of
      "controllable lifestyle" has become a critical factor in medical students'
      decision-making process. We postulate that widespread implementation of resident
      work hour limitations would bolster medical students' interest in pursuing
      surgical careers. STUDY DESIGN: Students from New York University School of
      Medicine were surveyed about their attitudes toward work hour limitations and its
      effect on their interest in pursuing a surgical residency. One hundred thirty-two
      students participated. RESULTS: Nearly 95% of respondents believed that work hour
      limitations were a positive change and, if all other factors were equal, they
      would choose a training program that used work hour limitations over one that did
      not. The most common reasons cited in favor of limits were improvements in
      resident lifestyle (42%) and patient safety (34%). Fifty-three percent of
      respondents indicated that presence of work hour limitations alone would increase
      their interest in considering a surgical residency and only 2% of medical
      students indicated that it would lessen their interest in surgery. Not
      surprisingly, intellectual interest in a specialty was the most important factor
      in choosing a residency for 86% of students. Nevertheless, work hour limitations
      were designated a higher priority than future salary by 55% of medical students.
      CONCLUSIONS: The presence of work hour limitations has a positive impact on
      medical students' interest in surgery. Widespread implementation of work hour
      limitations may bolster the number of applications for surgical residency.

PMID- 15454149
TI  - Prognostic value of resident clinical performance ratings.
AB  - BACKGROUND: This study investigated the concurrent and predictive validity of end
      of-rotation (EOR) clinical performance ratings. STUDY DESIGN: Surgeon EOR ratings
      of residents were collected and compared with end-of-year (EOY) progress
      decisions and to EOR and EOY confidential judgments of resident ability to
      provide patient care without direct supervision. RESULTS: Eighty percent to 85%
      of EOR ratings were Excellent or Very Good. Five percent or fewer were Fair or
      Poor. Almost all residents receiving Excellent or Very Good EOR ratings also
      received positive EOR judgments about ability to provide patient care without
      direct supervision. Residents rated Fair or Poor received negative EOR judgments
      about ability to provide patient care without direct supervision. As the
      cumulative percent of Good, Fair, and Poor EOR ratings increased, the number of
      residents promoted without stipulations at the end of the year decreased and the
      percentage of faculty members who judged the residents capable of providing
      effective patient care without direct supervision at the end of the year
      declined. All residents receiving 40% or more EOR ratings below Very Good had
      stipulations associated with their promotion. CONCLUSIONS: Despite use of
      descriptive anchors on the scale, clinical performance ratings have no direct
      meaning. Their meaning needs to be established in the same manner as is done in
      setting normal values for diagnostic tests, ie, by establishing the relationship
      between EOR ratings and practice outcomes.

PMID- 15454150
TI  - Intestinal malrotation-not just the pediatric surgeon's problem.

PMID- 15454151
TI  - Owen H Wangensteen, Jerome A Urban, and the pursuit of extraaxillary lymph node
      metastases from breast cancer.

PMID- 15454152
TI  - A report on accrual rates for elderly and minority-ethnicity cancer patients to
      clinical trials of the American College of Surgeons Oncology Group.
AB  - BACKGROUND: Incidence and mortality rates for cancers vary by ethnic background
      and patient age. Accrual of diverse patient populations to cancer clinical trials
      is essential in order to ensure that findings related to new management
      strategies can be generalized. The goal of this study was to evaluate accrual
      patterns for patients participating in the American College of Surgeons Oncology
      Group (ACOSOG) cancer protocols. Ethnic diversity among clinical trial
      investigators may also influence accrual patterns, so the ethnic background of
      the ACOSOG membership was also evaluated. STUDY DESIGN: Demographics for the
      patients registered on ACOSOG breast, thoracic, and colorectal clinical trials
      were evaluated and compared with data on the general population and the cancer
      population in the United States. Accrual patterns for patients from other
      reported cancer clinical trials were also presented, and the self-reported ethnic
      distribution of the ACOSOG membership was analyzed. RESULTS: Distribution of
      African Americans, Hispanic Americans, and Asian Americans to the ACOSOG breast
      and colorectal clinical trials was relatively proportionate to the cancer
      population. African Americans were underrepresented in the thoracic clinical
      trials, and this disparity was partially offset by data on the proportion of
      African Americans with stage-eligible lung cancer. Accrual rates for patients age
      65 years and older were better than those reported by most other clinical
      trialists. CONCLUSIONS: Elderly patients are successfully recruited into surgical
      clinical trials, and this will provide important data for future analyses
      regarding cancer outcomes in this growing population of cancer patients.
      Aggressive outreach to minority-ethnicity cancer patients for accrual into
      clinical trials should continue.

PMID- 15454153
TI  - Surgical excision of the hemivertebra in congenital scoliosis.

PMID- 15454154
TI  - Disseminated plasmablastic lymphoma.

PMID- 15454155
TI  - Reconstruction of middle hepatic vein using a rotating left hepatic vein flap.

PMID- 15454156
TI  - Biliary reconstruction using the cystic duct in right lobe living donor liver
      transplantation.

PMID- 15454157
TI  - Ibn Zuhr and experimental tracheostomy and tracheotomy.

PMID- 15454159
TI  - Use of statewide administrative database in assessing a regional trauma system.

PMID- 15454160
TI  - Protection of an esophageal anastomotic site.

PMID- 15454162
TI  - Major hepatectomy with simultaneous pancreatectomy.

PMID- 15454164
TI  - Giant fibroids.

PMID- 15454166
TI  - Clinical impact of cytokine gene polymorphisms in heart and lung transplantation.

PMID- 15454167
TI  - Mechanical Circulatory Support Device Database of the International Society for
      Heart and Lung Transplantation: second annual report--2004.

PMID- 15454168
TI  - Enhanced clinical utility of de novo cyclosporine C2 monitoring after lung
      transplantation.
AB  - BACKGROUND: The 2-hour post-cyclosporine (CyA) dose concentration (C2) is favored
      as the best single-point correlate of CyA area-under-the-concentration curve. CyA
      nephrotoxicity is a prominent cause of renal dysfunction that affects 38% of lung
      transplant (LTx) recipients at 5 years. METHODS: We assessed the utility of de
      novo C2 monitoring after LTx by comparing 2 sequential groups of 18 bilateral LTx
      recipients followed with traditional de novo trough CyA (C0) monitoring and de
      novo C2 monitoring, respectively. Target C0 levels were 450 microg/liter and 250
      microg/liter at 1 week and 3 months (3/12). Target C2 levels were 1,200
      microg/liter and 800 microg/liter. Groups were matched for anthropometrics and
      diagnoses. Baseline serum creatinine (Cr) was lower in the C0 group than in the
      C2 group (65 +/- 17 vs 81 +/- 21 micromol/liter, p = 0.02). RESULTS: At 3 months,
      survival for both groups was 100%, but the C0 group had a greater increase in Cr
      from baseline (90 +/- 54% vs 33 +/- 23%, p < 0.001) despite similar CyA dosage
      (6.6 +/- 3.8 vs 6.5 +/- 2.9 mg/kg/day, p = 0.94). There was no difference in
      forced expiratory volume in 1 second (% predicted) (71 +/- 16 vs 69 +/- 14, p =
      0.68), mean acute vascular rejection score per patient (2.61 +/- 2.12 vs 1.44 +/-
      1.72, p = 0.079), mean bronchial rejection score per patient (3.72 +/- 1.81 vs
      2.83 +/- 1.58, p = 0.126) or rate of infection (1.85 vs 1.79 events per 100
      patient-days). CONCLUSIONS: De novo C2 monitoring, which reduces both the risk of
      CyA toxicity and the risk of sub-therapeutic dosing, is a safe and effective
      technique for short-term preservation of renal function after LTx.

PMID- 15454169
TI  - Pediatric heart transplantation for anthracycline cardiomyopathy: cancer
      recurrence is rare.
AB  - BACKGROUND: Although anthracycline therapy is invaluable for treating neoplastic
      disorders, morbidity includes severe cardiomyopathy that leads to heart
      transplantation. This multicenter study describes the course of children who
      experienced anthracycline cardiomyopathy (ACM) and who subsequently required
      heart transplantation. METHODS: We reviewed transplant databases/registries at 4
      pediatric heart transplant centers to identify children with ACM who were listed
      for heart transplantation. We reviewed medical records to determine cancer
      therapy, clinical course, and outcome. RESULTS: Eighteen patients were listed,
      and 17 underwent transplantation. Mean age at cancer diagnosis was 6.0 years (SD,
      3.7). The mean anthracycline dose was 361 mg/m2 (SD, 110). The median time from
      cancer diagnosis to listing for heart transplantation was 9.2 years (range, 0.4
      15.2 years). Six transplantations were performed in patients who had disease-free
      intervals of <5 years. Two patients were lost to follow-up, and 8 are alive at
      4.9 years (SD, 2.0; range, 1.3-7.4 years) after transplantation. Seven patients
      died at 4.7 years (SD, 2.0; range, 1.2-7.1 years) after transplantation. One
      patient had recurrent cancer. One-, 2- and 5-year survivals were 100%, 92%, and
      60%, respectively. CONCLUSIONS: Cardiomyopathy that progresses to the need for
      heart transplantation occurs in patients receiving a wide range of cumulative
      anthracycline doses. The time from chemotherapy to ACM varies. Outcomes after
      transplantation are acceptable, and cancer recurrence is rare. Reconsideration of
      the 5-year disease-free wait period is warranted.

PMID- 15454170
TI  - Cardiotropic viruses in the myocardium of children with end-stage heart disease.
AB  - BACKGROUND: Transplantation has become a lifesaving procedure for children with
      end-stage heart failure. The long-term outcome for children who undergo
      transplantation has been of considerable interest, but the causes of graft
      failure and death are largely unknown, and the role of pre-transplant viral
      infection is unclear. METHODS: Myocardial samples from 80 explanted hearts from
      children with end-stage heart disease caused by congenital heart disease (CHD),
      cardiomyopathy, or chronic rejection were analyzed using polymerase chain
      reaction and reverse-transcriptase polymerase chain reaction for cardiotropic
      viruses using virus-specific primers. We used immunohistochemical analysis of
      cytoskeletal proteins to evaluate myocyte architecture. RESULTS: We identified
      parvoviral genomes in 6 patients (3 with CHD and 3 with cardiomyopathy). We
      detected no other viruses. Immunohistochemistry showed normal staining for key
      components of the cytoskeleton/sarcolemma, sarcomere, and nuclear membrane in the
      6 virus-positive samples. The clinical outcome of these children was worse (4
      long-term survivors, but 2 deaths) than for individuals without the genome.
      CONCLUSIONS: Detecting viruses within the myocardium at the point of end-stage
      heart failure is not common, regardless of the primary pathology. However, the
      presence of viruses may result in poor outcome for the patient.

PMID- 15454171
TI  - Bronchoalveolar lavage cytokine profile in a cohort of lung transplant
      recipients: a predictive role of interleukin-12 with respect to onset of
      bronchiolitis obliterans syndrome.
AB  - BACKGROUND: Bronchiolitis obliterans syndrome is the main long-term complication
      of lung transplantation that limits survival of lung transplant patients. Its
      pathophysiologic mechanisms are still poorly understood but it seems to result
      from a chronic immunologic/inflammatory insult leading to excessive
      fibroproliferation. The aim of this longitudinal study of 44 lung recipients was
      to determine whether a number of bronchoalveolar lavage and clinical variables
      are associated with a higher risk of developing bronchiolitis obliterans
      syndrome. METHODS: Bronchoalveolar lavage studies involved assessment of several
      cytokines including: interleukin-8, monocyte chemoattractant protein-1, regulated
      upon-activation normal T cell expressed and secreted (RANTES), gamma-interferon,
      interleukin-12, interleukin-10 and transforming growth factor-beta. RESULTS: The
      predictivity of bronchoalveolar lavage (BAL) features with respect to onset of
      bronchiolitis obliterans syndrome was assessed by the Cox regression model. Among
      clinical variables, bacterial and viral infections were found to significantly
      predict occurrence of bronchiolitis obliterans syndrome (hazard ratio [HR] for
      bacterial infection: 13.044, 95% confidence interval [CI] 1.34 to 126.69, p =
      0.027; HR for viral infections: 4.88, 95% CI 1.004 to 22.87, p = 0.05). Among BAL
      variables, only IL-12 was significantly predictive of bronchiolitis obliterans
      syndrome (HR 0.956, 95% CI 0.901 to 1.01, p = 0.03). In addition, in a sub-group
      cross-sectional analysis, bronchiolitis obliterans syndrome patients were
      compared with clinically stable patients, and significant increases in median
      levels of interleukin-8 and monocyte chemoattractant protein-1 BAL fluid were
      detected. CONCLUSIONS: These findings support the contention that interleukin-12
      plays a role in the modulation of the local pro-/anti-fibrotic balance of
      allograft airways.

PMID- 15454172
TI  - Administration of a tumor necrosis factor inhibitor at the time of myocardial
      infarction attenuates subsequent ventricular remodeling.
AB  - BACKGROUND: Tumor necrosis factor (TNF) causes myocardial extracellular matrix
      remodeling and fibrosis in myocardial infarction and chronic heart failure
      models. Pre-clinical and clinical trials of TNF inhibition in chronic heart
      failure have shown conflicting results. This study examined the effects of the
      administration of a TNF inhibitor immediately after myocardial infarction on the
      development of heart failure. METHODS: Lewis rats underwent coronary artery
      ligation and then received either intravenous etanercept (n = 14), a soluble
      dimerized TNF receptor that inhibits TNF, or saline as control (n = 13).
      Leukocyte infiltration into the infarct borderzone was evaluated 4 days post
      ligation in 7 animals (etanercept = 4, control = 3). After 6 weeks, the following
      parameters were evaluated in the remaining animals: cardiac function with a
      pressure-volume conductance catheter, left ventricular (LV) geometry, and
      borderzone collagenase activity. RESULTS: Etanercept rats had significantly less
      borderzone leukocyte infiltration 4 days post-infarction than controls (10.7 +/-
      0.5 vs 18.0, +/-2.0 cells/high power field; p < 0.05). At 6 weeks, TNF inhibition
      resulted in significantly reduced borderzone collagenase activity (110 +/- 30 vs
      470 +/- 140 activity units; p < 0.05) and increased LV wall thickness (2.1 +/-
      0.1 vs 1.8 +/- 0.1 mm, p < 0.05). Etanercept rats had better systolic function as
      measured by maximum LV pressure (84 +/- 3 mm Hg vs 68 +/- 5 mm Hg, p < 0.05) and
      the maximum change in left ventricular pressure over time (maximum dP/dt) (3,110
      +/- 230 vs 2,260 +/- 190 mm Hg/sec, p < 0.05), and better diastolic function as
      measured by minimum dP/dt (-3,060 +/- 240 vs -1,860 +/- 230 mm Hg/sec; p < 0.05)
      and the relaxation time constant (14.6 +/- 0.6 vs 17.9 +/- 1.2 msec; p < 0.05).
      CONCLUSIONS: TNF inhibition after infarction reduced leukocyte infiltration and
      extracellular matrix turnover and preserved cardiac function.

PMID- 15454173
TI  - Acceptance of related and unrelated cardiac allografts in neonatally tolerized
      mice is cardio-specific and transferable by regulatory CD4+ T cells.
AB  - BACKGROUND: Non-donor-specific cardiac allograft acceptance is induced in C3H/He
      (C3H; H-2k) recipients injected as neonates with allogeneic BALB/c (BALB; H-2d)
      fetal liver cells (FLC). This occurs despite intact reactivity to donor-type and
      third-party alloantigens in in vitro assays and skin transplants. To investigate
      a role for regulatory T cells, we performed adoptive transfer studies and
      specifically assessed CD4+ and CD4- T cells. METHODS: Three cell populations
      (splenocytes, CD4+, CD4-) derived from neonatally-treated mice with accepted
      C57BL/6 (B6; H-2b) third-party cardiac grafts were adoptively transferred into
      sub-lethally-irradiated C3H mice. Reconstituted mice were challenged with B6
      cardiac grafts, B6 skin grafts, or unrelated cardiac grafts. Separated cells were
      assessed in vitro. RESULTS: B6, BALB, and NZW (H-2z) graft acceptance was
      transferred by unfractionated splenocytes. CD4+ cells transferred B6 graft
      acceptance (85% survival > 100 days). CD4- cells, unfractionated cells from naive
      or only irradiated mice, and unfractionated cells from neonatally-treated non
      transplanted C3H mice rejected grafts within 35 days. No inoculum induced skin
      graft acceptance. Co-cultured assays confirmed the suppressive function of CD4+
      cells in vitro. CONCLUSIONS: Cardiac allograft acceptance in our model is
      regulated by CD4+ cells. The regulatory cell population is induced by the cardiac
      graft itself and mediates in vivo cardiac graft acceptance in a tissue-specific
      but not donor-strain-specific manner.

PMID- 15454174
TI  - Inhibition of alloresponse by a human trophoblast non-coding RNA suppressing
      class II transactivator promoter III and major histocompatibility class II
      expression in murine B-lymphocytes.
AB  - BACKGROUND: Trophoblasts are a model of natural allograft tolerance. A unique
      characteristic is the complete lack of expression of all classic major
      histocompatibility (MHC) antigens. We cloned a human trophoblast non-coding RNA
      (TncRNA) that suppresses MHC class II expression through inhibition of the class
      II transactivator (CIITA) promoter. We assessed the functional affects of TncRNA
      on an alloresponse and dissected the functional domain on CIITA promoter III.
      METHODS: Murine B-cell line A20 was transfected with TncRNA. Class II suppressed
      clones were selected and characterized by flow cytometry and Northern analysis.
      The clones were then subjected to lymphocyte proliferation assay to assess the
      stimulation of T-lymphocytes. CIITA promoter III-luciferase reporter plasmids
      were used with TncRNA plasmids in co-transfection assays; 5'-end deletion
      plasmids were used to dissect the promoter. RESULTS: Significant suppression of I
      Ad expression was seen. Northern blot scans demonstrated 84% to 93% suppression
      of class II transcripts. Lymphocyte proliferation assay demonstrated a 50% and
      64% inhibition of lymphocyte stimulation in the 2 clones, compared to A20 wild
      type. Dissection of promoter III indicated that an area between bp -152 to -107
      contains the functional site of TncRNA. CONCLUSION: Human TncRNA is active across
      species lines and significantly inhibits allogenic response to B-cells. There is
      concurrent suppression of constitutive class II expression in TncRNA clones
      mediated through a defined region of CIITA promoter III.

PMID- 15454175
TI  - A prospective study of continuous intravenous milrinone therapy for status IB
      patients awaiting heart transplant at home.
AB  - BACKGROUND: We performed a prospective study to determine the feasibility and
      safety of continuous intravenous milrinone therapy administered at home in
      patients listed as Status IB for heart transplant. METHODS: Patients who were
      Status IB could participate if they met specific criteria including an optimal
      dose of milrinone < or =0.5 microg/kg/min, presence of an implantable
      cardioverter-defibrillator (ICD), and no other serious comorbidity. The primary
      end-point of the study was survival to transplant. Hospitalizations, quality of
      life and cost comparisons were assessed. RESULTS: From May 1999 through October
      2002, a total of 60 patients (51 men, 9 women), aged 55.5 +/- 8.4 years, entered
      the study. Before milrinone therapy, cardiac index was 1.98 +/- 0.66
      liters/min/m2 and peak oxygen consumption was 11.4 +/- 2.6 ml/kg/min. Mean time
      in the study was 160.1 +/- 151.8 days. Fifty-three patients (88.3%) underwent
      heart transplant. There were only 2 deaths during the study. There were 89
      hospital admissions in 46 patients over the 43-month follow-up period; 58 of
      these admissions were for heart failure. There were 6 episodes of ICD firing for
      ventricular tachycardia. Quality-of-life measures in a sub-group of patients
      significantly improved 1 month after discharge. Substantial estimated cost
      savings occurred. CONCLUSIONS: Continuous intravenous milrinone therapy can be
      safely administered at home in selected patients with advanced heart failure who
      are listed for transplant. This strategy may be an acceptable alternative to
      prolonged hospitalization for patients dependent on continuous inotropic support.
      Re-hospitalization is to be expected. An implantable cardioverter-defibrillator
      should be present due to the incidence of ventricular tachycardia.

PMID- 15454176
TI  - Early expression of adhesion molecules after lung transplantation: evidence for a
      role of aggregated P-selectin-positive platelets in human primary graft failure.
AB  - BACKGROUND: Primary graft failure (PGF) secondary to ischemia-reperfusion injury
      is the main cause of death in the first month after lung transplantation. The aim
      of this study was to identify early cellular and immunologic events associated
      with PGF in human lung transplants. METHODS: Induction of P-selectin, E-selectin
      and intercellular adhesion molecule-1 (ICAM-1) and evaluation of leukocytes and
      platelets accumulation were investigated in 18 post-reperfusion surgical
      specimens of lung allografts by an immunohistochemical technique. RESULTS:
      Selectins were restricted to the venular plexus after reperfusion as in the
      normal lung, whereas ICAM-1 was induced in all cases on alveolar capillaries.
      Numerous polymorphonuclear cells (18 of 18 cases) and aggregated platelets (7 of
      18 cases) were identified along the venular plexus after reperfusion. Compared
      with the other patients, those with aggregated P-selectin-positive platelets were
      characterized by a longer duration of mechanical ventilation (p < 0.01), a lower
      PaO2/FiO2 ratio (p < 0.01) and the presence of radiologic edema (p < 0.05) within
      the first 3 post-operative days. CONCLUSIONS: We showed in the reperfused lung a
      distinct expression of adhesion molecules on venous and capillary pulmonary
      endothelia that may influence the role of leukocytes and platelets during the
      early course of transplantation. Furthermore, the knowledge of an association
      between the presence of P-selectin-positive platelet aggregates and PGF criteria
      might have implications for graft management and therapeutic strategies.

PMID- 15454177
TI  - Heterotopic rat heart transplantation: severe loss of glutathione in 8-hour
      ischemic hearts.
AB  - BACKGROUND: Tissue damage caused by reactive oxygen species (ROS) formed during
      ischemia/reperfusion seems to be an important risk factor in the failure of
      transplanted hearts. Although endogenous anti-oxidants protect the myocardium
      against free radical attack under physiologic conditions, their capacity may
      become limited during severe oxidative stress. Thus, we investigated the effect
      of 8-hour cold ischemia on the myocardial anti-oxidative defense system in a
      heterotopic rat heart transplantation model. METHODS: Lewis rat hearts were
      subjected to 30 or 480 minutes of 4 degrees C cold ischemia in Bretschneider
      cardioplegic solution with or without transplantation and reperfusion (30 or 240
      minutes) into F344 recipients. Activity levels of superoxide dismutase, catalase,
      glutathione peroxidase, glutathione reductase and glutathione S-transferase
      (GST), and concentrations of glutathione (GSH), glutathione disulfide (GSSG) and
      lipid hydroperoxides (LOOH) were analyzed in heart homogenates. For histology,
      cross-sections of the ventricles were stained with hematoxylin-eosin. RESULTS:
      Except for GST, enzyme activities and GSSG concentration increased and the
      glutathione redox ratio (GSH/GSH + 2GSSG) significantly decreased in 480-minute
      ischemic hearts compared with those with 30-minute ischemia. Reperfusion
      dramatically decreased both GSH and GSSG and increased LOOH formation but without
      severe histopathologic findings in the transplants. Applying a tree-structured
      classifier technique, GSH and LOOH were identified as significant features
      indicative of transplantation-induced oxidative stress. CONCLUSIONS: In the
      present study severe loss of glutathione and formation of LOOH indicated
      transplantation-induced oxidative stress in the rat heart; therefore, alterations
      of these parameters may hint at relevant deficits in the myocardial anti
      oxidative defense and may also predict subsequent tissue damage.

PMID- 15454178
TI  - Depression in pediatric patients before and 1 year after heart or heart-lung
      transplantation.
AB  - BACKGROUND: Although depression is a significant psychiatric condition of
      childhood and adolescence and those with a chronic medical problem are at
      increased risk for developing depression, the prevalence of depression in
      children and adolescents undergoing heart and heart-lung transplantation has not
      been addressed. However, the role of psychosocial factors, such as mood state, in
      determining outcome is being increasingly acknowledged. METHODS: The Mood and
      Feelings Questionnaire, a rating scale of depressive symptoms, was administered
      to 58 children before transplantation and to 46 children after transplantation,
      with 24 completing both assessments. To compare children's and parents' ratings,
      both child and parent versions, with corresponding items, were utilized. RESULTS:
      Pre-transplant, the mean score on the child measure was significantly higher (p <
      0.001) than that on the parent measure, with 24% and 21% on the child and parent
      measures, respectively, obtaining scores indicative of depression. Parents of
      children with acquired heart disease rated their children as having significantly
      more depressive symptoms than parents of children with congenital heart disease
      or cystic fibrosis. After transplantation, there was a reduction in mean scores
      on both the child and parent questionnaires and the pre-transplant differences
      between the different diagnostic groups were no longer apparent. Over time the
      numbers obtaining scores indicative of depression decreased by approximately 50%.
      CONCLUSIONS: Transplantation is associated with a reduction in the prevalence of
      depressive symptomatology. The role of original diagnosis in the manifestation of
      depression both before and after transplantation requires further investigation.

PMID- 15454179
TI  - Parent-reported health status after pediatric thoracic organ transplant.
AB  - BACKGROUND: Thoracic organ transplantation is a life-changing event for a child
      and family from both a physical and a psychosocial perspective. Accurate pre
      transplantation counseling and effective post-transplantation follow-up depend on
      a good understanding of post-transplantation health status, especially as
      perceived by families. METHODS: The Child Health Questionnaire-Parent Form 50
      (CHQ-P50), an instrument that assesses parent-reported health status of pediatric
      patients, was administered to 47 pediatric thoracic organ transplant recipients
      (41 heart, 6 lung) 5 to 18 years of age. RESULTS: Transplant recipients scored
      lower on the Physical Health Summary (PhS) score than the general population, as
      evidenced by a lower median score (50.6 vs 55.1, p < 0.0001) and a difference in
      the distribution of quartiles (p = 0.001), skewed toward the lower quartiles of
      the general population. The distribution of PhS scores in transplant recipients
      was comparable to scores of 3 groups of pediatric patients with other chronic
      health conditions (juvenile rheumatoid arthritis, epilepsy and asthma). The
      distribution of the Psychosocial Health Summary (PsS) scores was similar to that
      of the general population, but the median score was lower (51.5 vs 53.2, p =
      0.02). Transplant patients clearly scored lower than the general population on 4
      of 12 sub-scales, including those assessing general health, physical functioning,
      family activities and parental emotional impact. No difference was found in sub
      scales reflecting self-esteem, mental health, behavior, pain, peer interactions,
      family cohesion or parental time demands. CONCLUSIONS: Thoracic organ
      transplantation in children ages 5 to 18 years is associated with an ongoing
      deficit in parent-perceived physical health status.

PMID- 15454180
TI  - Sideroblastic anemia due to linezolid in a patient with a left ventricular assist
      device.
AB  - An acquired form of sideroblastic anemia has been described in association with
      several drugs, especially anti-microbial agents. A case of sideroblastic anemia
      is presented in a patient with a left ventricular assist device drive-line
      infection who was receiving linezolid, an antibiotic used for serious infections
      with gram-positive organisms. This patient's anemia resolved after
      discontinuation of the drug; he subsequently underwent an uncomplicated
      orthotopic heart transplant with no recurrence of anemia. As linezolid has been
      shown to have hematologic side effects, blood count monitoring is recommended in
      patients receiving this drug for long-term therapy.

PMID- 15454181
TI  - Limitations of listing criteria for heart transplantation in the United States:
      call for a critical review.

PMID- 15454183
TI  - Evaluation of an anti-rPA IgG ELISA for measuring the antibody response in mice.
AB  - A recombinant protective antigen (rPA)-based enzyme-linked immunosorbent assay
      (ELISA) was developed to measure the serological response of female A/J mice
      after inoculation with the new rPA-based anthrax vaccine. Several fundamental
      parameters of the ELISA were evaluated: specificity, precision, accuracy,
      linearity, and stability. Experimental results suggested that the quantitative
      anti-rPA IgG ELISA could be used to measure antibody levels in female A/J mice
      and may be useful as a potency assay to monitor consistency of manufacture of a
      rPA-based vaccine for planned clinical trials.

PMID- 15454184
TI  - Analysis of site-specific glycosylation in recombinant human follistatin
      expressed in Chinese hamster ovary cells.
AB  - Follistatin (FS), a glycoprotein, plays an important role in cell growth and
      differentiation through the neutralization of the biological activities of
      activins. In this study, we analyzed the glycosylation of recombinant human FS
      (rhFS) produced in Chinese hamster ovary cells. The results of SDS-PAGE and MALDI
      TOF MS revealed the presence of both non-glycosylated and glycosylated forms. FS
      contains two potential N-glycosylation sites, Asn95 and Asn259. Using mass
      spectrometric peptide/glycopeptide mapping and precursor-ion scanning, we found
      that both N-glycosylation sites were partially glycosylated. Monosaccharide
      composition analyses suggested the linkages of fucosylated bi- and triantennary
      complex-type oligosaccharides on rhFS. This finding was supported by mass
      spectrometric oligosaccharide profiling, in which the m/z values and elution
      times of some of the oligosaccharides from rhFS were in good agreement with those
      of standard oligosaccharides. Site-specific glycosylation was deduced on the
      basis of the mass spectra of the glycopeptides. It was suggested that biantennary
      oligosaccharides are major oligosaccharides located at both Asn95 and Asn259,
      whereas the triantennary structures are present mainly at Asn95.

PMID- 15454185
TI  - A microassay for measurement of Fc function of human immunoglobulin preparations
      by using tetanus toxoid as antigen.
AB  - In order to minimize possible adverse reactions, the functional integrity of
      proteins in products derived from human plasma has to be unaffected by methods of
      preparation and storage conditions. Numerous biologically relevant functions of
      IgG, a major component of immunoglobulin for intravenous use preparations (IVIG),
      rely on the integrity of Fc fragments. Manufacturers are obliged to prove that Fc
      mediated functions are maintained in IVIG preparations. The European
      Pharmacopoeia's monograph proposes a Rubella antigen-based test for Fc function
      of immunoglobulins. We present a modification of the proposed method achieved by
      using more convenient and readily available tetanus toxoid as an alternative
      antigen target and by adapting the procedure for the use on microtitre plates,
      thus greatly enhancing its feasibility and sample throughput. The test conditions
      were optimized so that batch-to-batch variability in tetanus antibody content did
      not influence the result. The precision of the test was within +/- 5%. By using
      this test, we compared Fc functionality of 9 commercial IVIG-7S preparations,
      which were prepared by using different virus inactivation/removal approaches. No
      significant differences between them have been found.

PMID- 15454186
TI  - The implications of using mutagenic primers in combination with Taq polymerase
      having proofreading activity.
AB  - Polymerases with proofreading activity provide high fidelity PCR amplifications.
      In this study we examined the consequences of using a Taq polymerase with
      proofreading activity, such as Optimase Taq polymerase, in combination with 4
      different mutagenic reverse primers for the amplification of a 345-bp FII PCR
      product. The amplifications were performed with Optimase Taq polymerase
      (Transgenomic), and Taq DNA polymerase-recombinant (Invitrogen), without
      proofreading activity. Mutation screening was carried out by DHPLC and
      restriction fragment analysis. The usage of Optimase Taq polymerase results in
      complete reversion of the first and second mutated nucleotide introduced at the
      3' end of the mutagenic reverse primer. It also partially reverses the missense
      nucleotide introduced in the third position of the mutagenic primer and leads to
      misleading DHPLC and restriction fragment analysis patterns. Nevertheless it
      cannot perform such an activity when an abnormal nucleotide is introduced in the
      fourth position.

PMID- 15454187
TI  - Evaluation of the bacterial endotoxin test for quantification of endotoxin
      contamination of porcine vaccines.
AB  - We investigated the application of the bacterial endotoxin test for the
      quantification of the endotoxin contamination of various commercial porcine
      vaccines. In endotoxin-spiked samples, Freund's complete adjuvant and aluminum
      hydroxide gel adjuvant failed to interfere with the results of the endotoxin
      test, and both recovery ratios were within the permissible range mentioned in the
      Japanese Pharmacopoeia. At the various dilutions tested, none of the adjuvants in
      commercial porcine vaccines caused noteworthy interference in the test. In
      addition, none of the 39 samples of porcine vaccines approved in Japan induced an
      interfering effect in the endotoxin test. Our findings suggest that the bacterial
      endotoxin test using endotoxin-specific Limulus amoebocyte lysate (LAL) can
      detect endotoxin contamination in commercial porcine vaccines containing either
      oil or aluminum adjuvants.

PMID- 15454188
TI  - Functional integrity of intravenous immunoglobulin following irradiation with a
      virucidal dose of gamma radiation.
AB  - Although intravenous immunoglobulins (IVIG) and other plasma therapeutics have
      had a relatively good safety record, improved methods for viral clearance are
      constantly being evaluated and incorporated into new manufacturing processes.
      Gamma irradiation has been used routinely to assure sterility of healthcare
      products and medical devices, but it has not been applied successfully as a viral
      inactivation method for biologics. We examine whether virucidal doses of gamma
      irradiation (50 kGy) can be delivered to a manufacturing intermediate form of
      IVIG, a fractionated plasma paste, with negligible effect on structural and
      functional integrity of purified IgG product. Immunoglobulins from paste were
      examined for radiation-induced damage by SDS-PAGE and ELISAs utilizing viral
      antigens specific for rubella, CMV and mumps. Fc domain integrity was assessed by
      immunoblotting, quantitatively comparing the binding of irradiated and non
      irradiated materials to cell surface Fcgamma receptors, and by employing
      quantitative RT-PCR to study the kinetics of accumulation of mRNA for the immune
      modulatory cytokines IL-1alpha, IL-1beta, IL-4, IL-8, IFNgamma, and TNFalpha. The
      results demonstrate that Fab and Fc domains of IVIG remain essentially intact and
      functional after gamma irradiation to virucidal doses, suggesting that this
      method could be used to enhance the safety of IVIG products.

PMID- 15454189
TI  - Seventh WHO informal consultation on standards for cytokines, growth factors and
      endocrinological substances.

PMID- 15454190
TI  - Breast cancer patients' experiences on endocrine therapy: monitoring with a
      checklist for patients on endocrine therapy (C-PET).
AB  - Women with hormone responsive breast cancer routinely receive endocrine therapy.
      There is growing evidence that patients experience significant side effects.
      Between 1996 and 1998, all patients on endocrine therapy for adjuvant or advanced
      breast cancer, attending the Edinburgh Breast Unit, were invited to complete a
      checklist for patients on endocrine therapy. This simple form, designed as a
      communication aid, was completed by patients before their consultation. 708
      patients (age 28-93) completed 1060 forms. These forms were analysed in order to
      gain a better understanding of the side effects experienced. Most patients were
      on tamoxifen (n = 524), with 103 on anastrazole and 35 on megestrol acetate.
      Common symptoms experienced were hot flushes, sweats and weight gain. Symptoms
      varied according to the patients' ages and the setting in which they received
      endocrine treatment. Pre-menopausal women were more likely to experience problems
      with flushes, sweats, weight gain and reduced libido.

PMID- 15454191
TI  - Characteristics and outcome of 1755 operable breast cancers in women over 70
      years of age.
AB  - From 1981 to 1995, 1755 patients aged 70 years or over who had nonmetastatic
      unilateral breast carcinoma received curative local or regional treatment in our
      institute. Median follow-up was 8 years. The median age of these patients was 75
      years (range: 70-94), and 86% were under 81 years of age. Tumors were classed as
      T3-4 in 24% of them; 18% had N1b/N2 tumors, and in 12% grade 3 disease was
      present. Only 19% were both ER and PR negative. The S phase fraction was <5% in
      79% of patients. In 1046 patients (60%) modified radical mastectomy was
      performed, while 20% underwent lumpectomy and in 20% radiotherapy was the only
      treatment administered. Adjuvant endocrine therapy was given in 463 (26%) cases,
      and only 3% of patients received chemotherapy. The median overall survival time
      was 121 months. The overall cancer-related death rate was 49%. The 10-year
      disease-free survival (DFS) rate was 64%, and the 10-year local relapse rate was
      14%. Prognostic factors determined on univariate analysis were tumor size,
      clinical nodal status (ER and PR), and grade. No significant difference in
      outcome was observed between mastectomy and conservative treatment. Parameters
      for which correlations with DFS were found on multivariate analysis were clinical
      nodal status (P < 0.0001), tumor size (P < 0.0001), ER (P < 0.0001), and PR (P =
      0.04). Breast cancer in elderly women is frequently hormone-dependent (81%) with
      a low proliferation index. Prognostic factors are the same as in younger
      postmenopausal patients. More than 50% of these patients died from a cause other
      than their breast cancer.

PMID- 15454192
TI  - Breast cancer on the Internet: the quality of Swedish breast cancer websites.
AB  - The aim of this study was to investigate the quality of Swedish-language breast
      cancer information available on the Internet. The questions explored were the
      extent and type of breast cancer information available, the coverage and
      correctness of that information, and whether the websites fulfilled the European
      Commission quality criteria for health-related websites. Three search engines
      were used to find websites containing medical information on breast cancer. An
      oncologist then evaluated the 29 relevant sites. Only seven of these were judged
      suitable for breast cancer patients. The coverage and correctness of the medical
      information varied considerably. None of the websites fulfilled the European
      Commission quality criteria. Therefore, considerable effort will be required
      before the Internet can serve as a valuable and up-to-date source of information
      on breast cancer for both professionals and laypersons. Our findings broadly
      match the results of earlier studies of English-language websites.

PMID- 15454193
TI  - Overexpression of Bmi-1 oncoprotein correlates with axillary lymph node
      metastases in invasive ductal breast cancer.
AB  - The modulation of Bmi-1 is observed in several tumor tissues, and its heightened
      protein level is suspected to be involved in tumorigenesis by acting as a
      transcriptional repressor in the INK4a/ARF locus. To elucidate the modulation of
      Bmi-1 in invasive ductal breast cancers, we examined its transcript and protein
      levels. The bmi-1 mRNA level by reverse transcription-polymerase chain reaction
      (RT-PCR) showed that it was significantly up-regulated in 28 specimens out of 33
      breast carcinoma tissues compared with those of non-neoplastic tissues just
      adjusted to tested specimens. Immunohistochemical staining for Bmi-1 also showed
      that 44 specimens out of 71 breast carcinoma tissues (62%) had strong positive
      signals with a more intense staining pattern in the invading fronts than in the
      central portions of primary invasive breast cancers. Univariate and multivariate
      analyses showed that a high level of Bmi-1 expression was significantly
      correlated with axillary lymph node metastases and positive estrogen receptor
      status. These findings suggested that Bmi-1 might be involved in the tumor
      progression and metastasis of invasive ductal breast cancer.

PMID- 15454194
TI  - Infiltrating lobular carcinoma--a comparison of diagnosis, management and outcome
      with infiltrating duct carcinoma.
AB  - The treatment and outcomes for 182 patients with lobular carcinoma were compared
      with 1612 patients with infiltrating ductal carcinoma managed concurrently at The
      Strathfield Breast Centre. The lobular carcinomas were larger (P < 0.0001) but of
      lower grade (P < 0.0001). Diagnosis with mammography and FNA was less sensitive
      in ILC (mammography P = 0.0002, FNA P < 0.0001). Although similar numbers of
      patients underwent initial attempted conservation, patients with ILC were more
      likely to have positive margins at attempted breast conservation surgery and the
      final mastectomy rate was higher (58.2% ILC versus 47% IDC, P = 0.0041). Of the
      patients who had successful conservation, the local recurrence rates for ILC
      (3.9%) were equivalent to the patients with IDC (5.3%). There was no significant
      difference in overall survival (90% ILC, 87% IDC, median follow-up 3.6 years ILC,
      4.3 years IDC) or disease free survival (87.9% ILC, 81.6% IDC). Although
      mastectomy is more likely to be necessary to obtain clear margins, breast
      conservation therapy is reasonable in patients with infiltrating lobular
      carcinoma where clear margins can be obtained.

PMID- 15454195
TI  - Cryoablation of benign breast tumors: evolution of technique and technology.
AB  - We report on improvements in cryoprobe design and techniques of cryoablation as a
      minimally invasive alternative to open surgery for the treatment of benign breast
      tumors. In the study, which was conducted in 12 centers, 124 lesions in 102
      patients were monitored for a period of 12 months after cryoablation. Two
      different treatment techniques were used: Double HI FREEZE and Tailored Freeze.
      In patients treated with the Tailored Freeze technique significantly better
      results were recorded 12 months after the procedure: the median reduction in
      tumor volume was 91%, 73% of all tumors treated were nonpalpable, 84% of lesions
      less than 2.5 cm in maximum diameter were nonpalpable, and none of the 31
      mammograms performed yielded abnormal findings. Patient satisfaction was good to
      excellent in 92% of the patients. The safety profile of this technique was
      excellent; all complications were minor. Evolution of cryoablation freezing
      techniques, coupled with improvements in cryoprobe design, has resulted in
      significant improvements in both safety and effectiveness.

PMID- 15454196
TI  - Lipoma of the breast: a diagnostic dilemma.
AB  - Lipoma of the breast often causes diagnostic and therapeutic uncertainty.
      Clinically it may be difficult to distinguish a lipoma from other conditions.
      Fine-needle aspiration cytology (FNAC) is often not helpful. Both mammography and
      ultrasound scanning are often negative. For the present study, 108 women with a
      clinical diagnosis of lipoma were enrolled prospectively. The clinical diagnosis
      of lipoma was found to be incorrect in 25.0% of these cases. Mammography and
      ultrasound revealed a lipoma in only 3.0% and 21.0%, respectively. FNAC revealed
      only fat cells in 74.0% of cases. In all, only 9 patients (11.4%) fulfilled the
      triple diagnostic criteria, theoretically making tumour excision mandatory in the
      remaining cases. Our proposal for management is for any clinical diagnosis of
      lipoma to be confirmed by either FNAC revealing fat cells or a core biopsy
      consistent with a lipoma. The mammogram and the ultrasound need not necessarily
      demonstrate a lipoma, but obviously must not show anything to raise the suspicion
      of malignancy at the site. If these criteria are met it is not necessary to
      excise the tumour.

PMID- 15454197
TI  - Syringomatous adenoma of the nipple.
AB  - Infiltrating syringomatous adenoma (SA) of the nipple is a rare but distinct
      benign clinical entity affecting the breast. It needs to be included in the
      differential diagnosis of patients who present with a lump in the nipple/areola
      complex. It is similar histologically to a syringoma, a benign tumour originating
      in the ducts of the dermal sweat glands, and importantly needs to be
      distinguished from a tubular carcinoma. SA of the nipple is locally infiltrating
      but is not known to metastasise. It often presents as a subareolar lesion with
      clinical, mammographic and ultrasound findings suspicious for malignancy. Whilst
      it may be possible to suspect the diagnosis on fine needle cytology, core biopsy
      or excisional biopsy is usually required to establish the diagnosis. There is a
      tendency to recurrence if excision is incomplete. The following is a case report,
      literature review and discussion of the surgical management options available in
      this unusual condition.

PMID- 15454198
TI  - Metastatic intramammary lymph nodes as the primary presenting sign of breast
      cancer.
AB  - Intramammary lymph nodes (IMLNs) are not uncommon, and are likely to be more
      frequently identified with the wider use of mammography and breast ultrasound.
      IMLNs could be invaded by breast cancer influencing the prognosis and the
      management of patients. The aim of this study is to present the very rare
      phenomenon of metastatic involvement of these nodes from an occult breast cancer.

PMID- 15454199
TI  - Cisplatin plus vinorelbine (PVn) as a salvage regimen for refractory breast
      cancer.
AB  - Breast cancer is regarded as a systemic disease even when tumors are completely
      resected. In patients with advanced breast cancer the overall prognosis is poor,
      but the disease is not uniformly fatal. Vinorelbine has proved to be effective
      when given as a single agent in this setting. Since it has a moderate to severe
      myelotoxic effect, a combination of vinorelbine with cisplatin, which is a weak
      myelotoxic drug, is ideal for the treatment of patients with advanced disease. In
      this paper, we report on a patient with advanced breast cancer who attained
      complete response of 14 months duration to a cisplatin/vinorelbine combination
      after progression during treatment with paclitaxel and doxorubicin.

PMID- 15454200
TI  - Gigantic Paget disease of the breast.
AB  - A rare case of gigantic Paget disease is presented. Surgical treatment and
      reconstructive issues are discussed in detail.

PMID- 15454201
TI  - Gynaecomastia and the plant product "Tribulis terrestris".
AB  - Gynaecomastia is the commonest benign breast condition seen in men. It is well
      recognised that certain drugs that alter the normal sex hormonal profile in the
      body can induce gynaecomastia. Recently, an increasing use of androgenic-anabolic
      steroids among young men especially body-builders has increased the incidence of
      gynaecomastia. We report a case of a young weight-trainer who developed
      gynaecomastia due to oral intake of a herbal tablet which he used as a steroid
      alternative for body-building.

PMID- 15454202
TI  - Pseudo-angiomatous stromal hyperplasia presenting as a breast mass: imaging
      findings in three patients.
AB  - The authors review the mammographic, ultrasonographic and magnetic resonance (MR)
      imaging findings in each of three patients with a breast tumor corresponding to
      the characteristics of pseudo-angiomatous stromal hyperplasia (PASH). Imaging
      findings are indistinguishable from those of the more common type of
      fibroadenoma, and they are categorised as BIRADS type 3 lesions (probably benign
      lesions). Their benign condition and behaviour compared with other similar cases,
      allows the recommendation that surgical excision be avoided, and the patients
      monitored with periodic follow-up. The diagnosis can be confidently established
      by sampling with a breast core biopsy in the case of any doubt about whether the
      lesion is benign if the patient is anxious.

PMID- 15454203
TI  - Primary breast lymphoma in a male patient.
AB  - Primary lymphoma of the male breast is extremely rare. We report a case of a
      diffuse large B-cell lymphoma in a male patient. A 67-year-old man presented with
      a palpable mass in the right breast and ipsilateral axillary lymphadenopathy. At
      operation a 6 x 5 x 4-cm mass was excised, and a frozen section demonstrated
      malignancy. A modified radical mastectomy was then performed, together with
      axillary lymph node clearance. Histological examination established the diagnosis
      of a primary non-Hodgkin's lymphoma of the breast. The patient was referred for
      chemotherapy and died a year later from systemic disease involving the adrenals.
      The importance of early diagnosis is emphasized; this should be based on an
      excisional biopsy or aspiration cytology. As patients with primary breast
      lymphoma (PBL) have a better prognosis than those with carcinoma of the breast or
      patients with extranodal lymphomas, a multidisciplinary approach including
      surgery, radiotherapy, and chemotherapy when needed would result in a more
      favorable outcome.

PMID- 15454204
TI  - Secretory breast cancer in a 7.5-year old boy.
AB  - Breast cancer is extremely rare in children, and consequently no consensus has
      been reached on the optimal treatment modalities. The medical history and
      treatment plan for a 7.5-year old male breast cancer patient is described.
      Radical mastectomy with sentinel node biopsy was performed in October 2002. As no
      malignant cells were detected in the sentinel node, and no BRCA1-2 mutations were
      detected, no further radio- or chemotherapy was performed. A "wait-and-see"
      policy was decided on. Further treatment will be given if this becomes necessary
      with the development of metastases.

PMID- 15454205
TI  - Synthesis and enzymatic evaluation of xanthine oxidase-activated prodrugs based
      on inhibitors of thymidine phosphorylase.
AB  - A series of xanthine oxidase-activated prodrugs of known inhibitors of thymidine
      phosphorylase has been designed and synthesised to introduce tumour selectivity.
      These prodrugs were oxidised by xanthine oxidase at C-2 and/or C-4 of the uracil
      ring to generate the desired TP inhibitor.

PMID- 15454206
TI  - Synthesis and structure-activity relationships of indole and benzimidazole
      piperazines as histamine H(4) receptor antagonists.
AB  - We describe the structure-activity relationships for a series of ligands
      structurally related to the recently identified (5-chloro-1H-indol-2-yl)-(4
      methyl-piperazin-1-yl)-methanone (1) as histamine H(4) receptor (H(4)R)
      antagonists. Furthermore, we identified related benzimidazoles as novel lead
      compounds for the H(4)R. The ligands have been evaluated by radioligand
      displacement studies and functional assays for their interaction with both the
      human histamine H(3) and H(4) receptors and exhibit pK(i) values up to 7.5 at the
      human H(4)R.

PMID- 15454207
TI  - Optimizing the antibacterial activity of a lead structure discovered by "SAR by
      MS" technology.
AB  - We report on lead optimization of a compound that was originally discovered to
      bind bacterial 23S rRNA near the L11 binding site and inhibit translation in
      vitro, but lacked detectable antibacterial activity. In this study, we were able
      to generate compounds with antibacterial activity against Gram-negative and Gram
      positive pathogens, including a methicillin-resistant S. aureus strain.

PMID- 15454208
TI  - SAR and factor IXa crystal structure of a dual inhibitor of factors IXa and Xa.
AB  - Modifications to the P4 moiety and pyrazole C3 substituent of factor Xa inhibitor
      SN-429 provided several new compounds, which are 5-10nM inhibitors of factor IXa.
      An X-ray crystal structure of one example complexed to factor IXa shows that
      these compounds adopt a similar binding mode to that previously observed with
      pyrazole inhibitors in the factor Xa active site both with regard to how the
      inhibitor binds and the position of Tyr99.

PMID- 15454209
TI  - 5-Amidinoindoles as dual inhibitors of coagulation factors IXa and Xa.
AB  - Structural features of a 5-amidinoindole inhibitor of factor Xa, which displayed
      modest inhibition of factor IXa were varied to increase potency and improve
      selectivity for factor IXa.

PMID- 15454210
TI  - Design and synthesis of 4-phenyl piperidine compounds targeting the mu receptor.
AB  - Small molecule mu agonists based on the 4-phenyl piperidine scaffold were
      designed and synthesized to further investigate the therapeutic potential of
      loperamide analogs. The resulting compounds show excellent agonistic activity
      towards the human mu receptor with interesting SAR trends within the series.

PMID- 15454211
TI  - Novel aryloxy-8-azabicyclo[3.2.1]oct-3-enes with 5-HT transporter and 5-HT1A
      affinity.
AB  - Joining aryl 8-azabicyclo[3.2.1]oct-3-enes with aryloxyethanes and
      aryloxypropanes produces novel series of compounds 11 and 12 with potent 5-HT-T
      affinity and moderately potent 5-HT(1A) affinity. Moreover, several of these
      compounds possess functional 5-HT(1A) antagonism. Optimal compounds are, 4
      indolyloxyethane 21, 4-indolyloxypropanes 25, and 27, which possess potent 5-HT-T
      affinity (5-HT-T K(i): 21: 1.2nM, 25: 0.54nM, 27: 0.38nM) and good 5-HT(1A)
      affinity/antagonism (5-HT(1A)K(i), [(35)S]GTPgammaS: E(max) (%): 21: 111.1nM, 0%;
      25: 173.2nM, 0%; 27: 107nM, 0%).

PMID- 15454212
TI  - Synthesis and structure-activity investigation of iodinated arylhydantoins and
      arylthiohydantoins for development as androgen receptor radioligands.
AB  - A series of side-chain derivatives of the arylhydantoin RU 58841 and the
      arylthiohydantoin RU 59063, wherein the aromatic trifluoromethyl group was
      replaced with iodine, was synthesized for possible development as radioiodinated
      androgen receptor (AR) ligands. Derivatives containing the cyanomethyl,
      methoxyethyl and propenyl side-chains displayed moderately high affinity (K(i)=20
      59nM) towards the rat AR. Side-chains containing bulky lipophilic groups such as,
      benzyl and phenylpropyl, were poorly tolerated (K(i)>219nM). Superior AR binding
      affinities (0.71nM<K(i)<11nM) were displayed by arylhydantoins and
      arylthiohydantoin derivatives containing hydroxybutyl or methyl side-chains. The
      latter compounds are potential candidates for development as radioiodinated AR
      ligands.

PMID- 15454213
TI  - Synthesis and antiproliferative activity of 2-aryl-4-oxo-thiazolidin-3-yl-amides
      for prostate cancer.
AB  - We have previously described serine amide phosphates (SAPs) as a novel class of
      cytotoxic agents for prostate cancer. Several of them showed potent cytotoxicity
      against human prostate cancer cell lines, but were not selective in non-tumor
      cells. To improve the selectivity and further enhance the potency, we designed a
      new series of 2-aryl-4-oxo-thiazolidin-3-yl amides. The current work describes
      synthesis, SAR, and biological evaluation of these compounds for their ability to
      inhibit the growth of prostate cancer cells. The antiproliferative effects of
      synthesized compounds were examined in five human prostate cancer cell lines (DU
      145, PC-3, LNCaP, PPC-1, and TSU), and in RH7777 cells (negative controls). From
      this study, three potent compounds (8, 20, and 21) have been detected, which are
      effective in killing prostate cancer cells with improved selectivity compared to
      SAPs.

PMID- 15454214
TI  - Dipeptidyl aspartyl fluoromethylketones as potent caspase inhibitors: SAR of the
      N-protecting group.
AB  - This article describes the synthesis and biological evaluation of a group of N
      protected Val-Asp-fmk as caspase inhibitors. The protecting group was found to
      contribute to caspase-3 inhibiting activity, and compounds with a large group
      such as Cbz are more active than compounds with a small group such as Ac.
      Compounds with more hydrophobic protecting groups were found to be more active in
      cell apoptosis protection assays, probably due to increased cell permeability.
      MX1122, 2,4-di-Cl-Cbz-Val-Asp-fmk, is identified as a potent broad-spectrum
      caspase inhibitor and is selective for caspases versus other proteases, with good
      activity in the cell apoptosis protection assays as well as good efficacy in the
      mouse liver apoptosis model.

PMID- 15454215
TI  - More potent linear peptide inhibitors of mammalian ribonucleotide reductase.
AB  - Mammalian ribonucleotide reductase (mRR) is a chemotherapeutic target. The enzyme
      is composed of two subunits (mR1 and mR2) and is inhibited by Ac-FTLDADF (denoted
      P7), corresponding to the C-terminus of mR2, which disrupts mRR quaternary
      structure by competing with mR2 for binding to mR1. The tripeptide FmocWFF acts
      similarly. Here we report on the use of small, focused libraries to identify Fmoc
      derivatives of tetra and hexapeptides having comparable or considerably higher
      activities than P7 toward inhibition of mRR.

PMID- 15454216
TI  - Design and synthesis of 1-(4-benzoylphenyl)imidazole derivatives as new potent 20
      HETE synthase inhibitors.
AB  - Structural modification of the novel 20-HETE synthase inhibitor 1 (IC(50) 310nM)
      is described. Introduction of a side chain with a carboxylic acid at the terminal
      position to 1 resulted in increased ability to inhibit human renal microsomal
      production of 20-HETE (7c: IC(50) 7.9nM), with good selectivity toward CYP2D6 and
      cyclooxygenases (COX)-1 and -2.

PMID- 15454217
TI  - Substrate analogs for the investigation of deoxyxylulose 5-phosphate
      reductoisomerase inhibition: synthesis and evaluation.
AB  - Deoxyxylulose 5-phosphate (DXP) analogs were synthesized and evaluated as
      alternative substrates and inhibitors of recombinant Synechocystis PCC6803 DXP
      reductoisomerase (DXR; EC 1.1.1.267). Five of the compounds tested (1,2-dideoxy-D
      threo-3-hexulose 6-phosphate, 1-deoxy-l-ribulose 5-phosphate, 2S,3R
      dihydroxybutyramide 4-phosphate, 4S-hydroxypentan-2-one 5-phosphate, and 3S
      hydroxypentan-2-one 5-phosphate) acted as relatively weak competitive inhibitors
      when compared to fosmidomycin. A sixth compound, 3R,4S-dihydroxy-5
      oxohexylphosphonic acid, served as an alternate substrate, as has recently been
      reported for the same compound with Escherichia coli DXR.

PMID- 15454218
TI  - Fluorescent sodium ion indicators based on the 1,7-diaza-15-crown-5 system.
AB  - A series of novel sodium ion-sensitive fluorescent reagents suitable for
      biological applications is described. The chelator nitrogen atom substituents
      affect the selectivity and affinity of cation binding, while the nature of the
      fluorophore determines the type of fluorescent response to metal ion chelation.

PMID- 15454219
TI  - Synthesis and activity of novel analogs of hemiasterlin as inhibitors of tubulin
      polymerization: modification of the A segment.
AB  - Analogs of hemiasterlin (1) and HTI-286 (2), which contain various aromatic rings
      in the A segment, were synthesized as potential inhibitors of tubulin
      polymerization. The structure-activity relationships related to stereo- and regio
      chemical effects of substituents on the aromatic ring in the A segment were
      studied. Analogs, which carry a meta-substituted phenyl ring in the A segment
      show comparable activity for inhibition of tubulin polymerization to 2, as well
      as in the cell proliferation assay using KB cells containing P-glycoprotein,
      compared to those of 1 and 2.

PMID- 15454220
TI  - Alkyl lysophosphatidic acid and fluoromethylene phosphonate analogs as
      metabolically-stabilized agonists for LPA receptors.
AB  - We describe an efficient method for the synthesis of alkyl lysophosphatidic acid
      (LPA) analogs as well as alkyl LPA mono- and difluoromethylene phosphonate
      analogs. Each alkyl LPA analog was evaluated for subtype-specific LPA receptor
      agonist activity using a cell migration assay for LPA(1) activation in cancer
      cells and an intracellular calcium mobilization assay for LPA(2) and LPA(3)
      activation. Alkyl LPAs induced pronounced cell migration activity with equivalent
      or higher potency than sn-1-oleoyl LPA, while the alkyl LPA fluoromethylene
      phosphonates proved to be less potent agonists in this assay. However, each alkyl
      LPA analog activated Ca(2+) release by activation of LPA(2) and LPA(3) receptors.
      Interestingly, the absolute configuration of the sn-2 hydroxyl group of the alkyl
      LPA analogs was not recognized by any of the three LPA receptors. The use of
      alkyl LPA analogs further expands the scope of structure-activity studies, which
      will better define LPA-LPA receptor interactions.

PMID- 15454221
TI  - Allosteric potentiators of the metabotropic glutamate receptor 2 (mGlu2). Part 1:
      Identification and synthesis of phenyl-tetrazolyl acetophenones.
AB  - We have identified and synthesized a series of aryl-tetrazoyl acetophenones as
      positive allosteric potentiators of the metabotropic glutamate receptor 2.
      Structure activity relationship studies directed toward improving the potency and
      level of potentiation led to the discovery of 22 (EC(50)=93nM, 128%
      potentiation).

PMID- 15454222
TI  - HCV NS5B polymerase-bound conformation of a soluble sulfonamide inhibitor by 2D
      transferred NOESY.
AB  - HCV NS5B RNA-dependent RNA polymerase (NS5B) is essential for viral replication
      and is therefore considered a target for antiviral drug development. From our
      ongoing screening effort in the search for new anti-HCV agents, a novel inhibitor
      1 with low microM activity against the HCV NS5B polymerase was identified. SAR
      analysis indicated the optimal substitution pattern required for activity, for
      example, carboxylic acid group at 2-position of thiophene ring. We describe the
      steps taken to identify and solve the bioactive conformation of derivative 6
      through the use of the transferred NOE method (trNOE).

PMID- 15454223
TI  - Three new compounds from the plant Lippia alva as inhibitors of chemokine
      receptor 5 (CCR5).
AB  - The 70% aqueous methanol extract of the Peruvian plant Lippia alva (Verbenaceae)
      was found to contain three novel compounds, 1, 2, and 3, which were identified as
      inhibitors of the chemokine receptor CCR5. The structures of 1-3 were established
      based on extensive NMR studies. Compounds 1-3 inhibited CCR5 receptor signaling
      as measured by a calcium mobilization assay with IC(50) values of 5.5, 6.0, and
      7.2 microg/mL, respectively.

PMID- 15454224
TI  - Novel histone deacetylase inhibitors: cyclic tetrapeptide with trifluoromethyl
      and pentafluoroethyl ketones.
AB  - Cyclic tetrapeptides containing trifluoromethyl and pentafluoroethyl ketone as
      zinc binding functional group were synthesized as potent HDAC inhibitors.
      Evaluation by human HDAC inhibition assay and p21 promoter assay showed that
      these inhibitors are promising anticancer agents.

PMID- 15454225
TI  - Bis[3-(4'-substituted phenyl)prop-2-ene]disulfides as a new class of
      antihyperlipidemic compounds.
AB  - A series of bis[3-(4'-substituted phenyl)prop-2-ene]disulfides were prepared and
      their hypolipidemic activities were examined in hypercholesterolemic Wistar rats.
      Introduction of an electron withdrawing group to the phenyl ring in the parent
      compound led to the identification of compound 8 as a potent and efficacious
      hypolipidemic agent.

PMID- 15454226
TI  - Synthesis of some newer analogues of substituted dibenzoyl phenol as potent anti
      inflammatory agents.
AB  - Benzoylation of hydroxybenzophenones 1a-f affords substituted benzoyl phenyl
      benzoates 3a-f, which on Fries rearrangement using microwave irradiation led to a
      facile synthesis of solely dibenzoyl phenols 4a-f in excellent yield. The newly
      synthesized compounds were screened for their anti-inflammatory activity and were
      compared with standard drugs. Out of the compounds studied, the compound 4e
      showed more potent activity than the standard drugs at all doses tested.

PMID- 15454227
TI  - In vitro plasma protein binding and aqueous aggregation behavior of astaxanthin
      dilysinate tetrahydrochloride.
AB  - The tetrahydrochloride salt of astaxanthin di-L-lysinate (lys(2)AST) is a highly
      water-dispersible astaxanthin-amino acid conjugate, with an aqueous
      dispersibility of > or = 181.6 mg/mL. The statistical mixture of stereoisomers
      has been well characterized as an aqueous-phase superoxide anion scavenger,
      effective at micromolar (microM) concentrations. In the current study, the
      aqueous aggregation behavior and in vitro plasma protein binding [with fatty-acid
      free human serum albumin (HSA) and alpha(1)-acid glycoprotein (AGP)] were
      investigated with a suite of techniques, including circular dichroism (CD) and UV
      vis spectroscopy, ultrafiltration, competitive ligand displacement, and
      fluorescence quenching. Induced CD bands obtained in Ringer buffer solution of
      HSA demonstrated high affinity monomeric binding of the compound at low ligand
      per protein (L/P) ratios (in aqueous solution alone the carotenoid molecules
      formed card-pack aggregates). The binding constant ( approximately 10(6)M(-1))
      and the binding stoichiometry (approximately 0.2 per albumin molecule) were
      calculated from CD titration data. CD displacement and ultrafiltration
      experiments performed with marker ligands of HSA indicated that the ligand
      binding occurred at a site distinct from the main drug binding sites of HSA
      (i.e., Sites I and II). At intermediate L/P ratios, both monomeric and aggregated
      ("chirally complexed") binding occurred simultaneously at distinct sites of the
      protein. At high L/P ratios, chiral complexation predominantly occurred on the
      asymmetric protein template. The tentative location of the chirally-complexed
      aggregation on the HSA template was identified as the large interdomain cleft of
      HSA, where carotenoid derivatives have been found to bind previously. Only weak
      binding to AGP was observed. These results suggest that parenteral use of this
      highly potent, water-dispersible astaxanthin-amino acid conjugate will result in
      plasma protein association, and plasma protein binding at sites unlikely to
      displace fatty acids and drugs bound at well-characterized binding sites on the
      albumin molecule.

PMID- 15454228
TI  - Design, synthesis, and activity of 4-quinolone and pyridone compounds as nonthiol
      containing farnesyltransferase inhibitors.
AB  - As a part of our efforts to identify potent inhibitors of farnesyltransferase
      (FTase), modification of the structure of tipifarnib through structure-based
      design was undertaken by replacing the 2-quinolones with 4-quinolones and
      pyridones, and subsequent relocation of the D-ring to the N-methyl group on the
      imidazole ring. This study has yielded a novel series of potent and selective
      FTase inhibitors. The X-ray structure of tipifarnib (1) in complex with FTase was
      described.

PMID- 15454229
TI  - Synthesis and activity of 1-aryl-1'-imidazolyl methyl ethers as non-thiol
      farnesyltransferase inhibitors.
AB  - A series of imidazole-containing methyl ethers (4-5) have been designed and
      synthesized as potent and selective farnesyltransferase inhibitors (FTIs) by
      transposition of the D-ring to the methyl group on the imidazole of the
      previously reported FTIs 3. Several compounds such as 4h and 5b demonstrate
      superior enzymatic activity to the current benchmark compound tipifarnib (1) with
      IC(50) values in the lower subnanomolar range, while maintaining excellent
      cellular activity comparable to tipifarnib. The compounds are characterized as
      being simple, easier to make, and possess no chiral center involved.

PMID- 15454230
TI  - Camptothecin analogs with bulky, hydrophobic substituents at the 7-position via a
      Grignard reaction.
AB  - By developing a new synthetic procedure for introduction of side chains onto the
      camptothecin ring system, we were able to achieve the preparation of a number of
      analogs bearing bulky, hydrophobic groups directly attached to the 7-position.
      These include 7-tert-butylcamptothecin, 7-benzylcamptothecin and the
      corresponding 10,11-methylenedioxycamptothecins. This method involves the
      reaction of an appropriate orthoaminobenzonitrile with various Grignard reagents
      to give the corresponding orthoaminoketones. Friedlander condensation of the
      latter with the key tricyclic ketone leads to 7-substituted camptothecin analogs.
      We report the activity of these compounds as topoisomerase I poisons and their
      ability to inhibit growth of selected tumor cell lines.

PMID- 15454231
TI  - A novel series of p38 MAP kinase inhibitors for the potential treatment of
      rheumatoid arthritis.
AB  - A novel p38 MAP kinase inhibitor structural class was discovered through
      selectivity screening. The rational analogue design, synthesis and structure
      activity relationship of this series of bis-amide inhibitors is reported. The
      inhibition in vitro of human p38alpha enzyme activity and lipopolysaccharide
      induced tumour necrosis factor-alpha release is described for the series. The
      activity in vivo and pharmacokinetic properties are exemplified for the more
      potent analogues.

PMID- 15454232
TI  - Novel, potent and selective anilinoquinazoline and anilinopyrimidine inhibitors
      of p38 MAP kinase.
AB  - SAR studies led to the identification of 4-(3-benzoylamino-6-methyl
      anilino)quinazolines as potent and selective inhibitors of p38 MAP kinase.
      Further optimisation led to the identification of a series of 4-(3-benzoylamino-6
      methyl-anilino)pyrimidines as potent inhibitors of the p38 MAP kinase signalling
      pathway in vitro and in vivo.

PMID- 15454233
TI  - Benzothienyloxy phenylpropanamines, novel dual inhibitors of serotonin and
      norepinephrine reuptake.
AB  - A series of benzothienyloxy propylamines have been prepared and are demonstrated
      to be inhibitors of both serotonin and norepinephrine reuptake.

PMID- 15454234
TI  - Synthesis and biological evaluation of thiazolidine-2,4-dione and 2,4-thione
      derivatives as inhibitors of translation initiation.
AB  - In an effort to generate novel translation initiation inhibitors for cancer
      therapy, a series of 2'-benzyloxy-5'-substituted-5-benzylidene-thiazolidine-2,4
      thione and dione derivatives was synthesized and evaluated for activity in
      translation initiation specific assays. Several candidates of the 5-benzylidene
      thiazolidine-2,4-diones (3c, 3d, and 3f) and -thiones (2b, 2e, and 2j), inhibit
      cell growth with low microM GI(50) mediated by inhibition of translation
      initiation, which involves partial depletion of intracellular Ca(2+) stores and
      strong phosphorylation of eIF2alpha.

PMID- 15454235
TI  - Small molecule inhibitors of the CCR2b receptor. Part 1: Discovery and
      optimization of homopiperazine derivatives.
AB  - N,N'-Disubstituted homopiperazine derivatives have been discovered as CC
      chemokine receptor 2b (CCR2b) inhibitors with submicromolar activity in the CCR2b
      binding assay. A 4-substituted benzyl group on one homopiperazine nitrogen was an
      important moiety for binding affinity to the CCR2b receptor. The SAR for CCR2b
      binding affinity correlated inversely with the sigma factor of the functional
      group on this benzyl moiety. Introduction of hydroxy groups to appropriate
      positions in the 3,3-diphenylpropyl group on the other homopiperazine nitrogen
      increased CCR2b binding activity. The synthesis of an informer library to search
      for alternative substructures is also described.

PMID- 15454236
TI  - Small molecule antagonists of the CCR2b receptor. Part 2: Discovery process and
      initial structure-activity relationships of diamine derivatives.
AB  - Structure-activity relationships (SAR) of a weakly active class of CCR2b
      inhibitors were utilized to initiate a lead evolution program employing the Drug
      Discovery Engine. Several alternative structural series have been discovered that
      display nanomolar activity in the CCR2b binding and CCR2b-mediated chemotaxis
      assays.

PMID- 15454237
TI  - Effect of gamma-hydroxypropano deoxyguanosine, the major acrolein-derived adduct,
      on monomolecular quadruplex structure of telomeric repeat d(TTAGGG)(4).
AB  - The three oligodeoxyribonucleotides (ODNs) a-c, having the telomeric repeat
      d(TTAGGG)(4) sequence and incorporating gamma-hydroxypropano deoxyguanosine at
      different positions, were synthesized. Gel electrophoresis and CD analyses
      indicated that the ODNs assume monomolecular quadruplex structures in Na+ and in
      K+ buffers. The T(m) values, obtained by CD melting experiments, showed that the
      presence of the acrolein-dG adduct into the ODN b decreases the thermal stability
      of the monomolecular quadruplex structure in Na+ solution, whereas for a and c no
      significant effect could be detected in the same experimental conditions. On the
      contrary, all ODNs a-d show the same behaviour in K+ buffer. These findings are
      briefly discussed.

PMID- 15454238
TI  - Microbial oxidation of terfenadine and ebastine into fexofenadine and
      carebastine.
AB  - The oxidation of tert-butyl-phenyl group of title compounds by some
      microorganisms was studied. We have optimized the conditions of culture to
      increase the formation of acid metabolites and to avoid the formation of side
      products. We showed that an oxidative activity is induced by soybean peptones in
      Streptomyces platensis. The biologically active compounds, fexofenadine and
      carebastine, are produced in good yield (86-95%) by Absidia corymbifera.

PMID- 15454239
TI  - Carbonic anhydrase inhibitors: synthesis and inhibition of cytosolic/tumor
      associated carbonic anhydrase isozymes I, II, and IX with sulfonamides
      incorporating 1,2,4-triazine moieties.
AB  - A series of benzenesulfonamide derivatives incorporating triazine moieties in
      their molecules was obtained by reaction of cyanuric chloride with sulfanilamide,
      homosulfanilamide, or 4-aminoethylbenzenesulfonamide. The dichlorotriazinyl
      benzenesulfonamides intermediates were subsequently derivatized by reaction with
      various nucleophiles, such as water, methylamine, or aliphatic alcohols (methanol
      and ethanol). The library of sulfonamides incorporating triazinyl moieties was
      tested for the inhibition of three physiologically relevant carbonic anhydrase
      (CA, EC 4.2.1.1) isozymes, the cytosolic hCA I and II, and the transmembrane,
      tumor-associated hCA IX. The new compounds reported here inhibited hCA I with
      K(I)s in the range of 75-136nM, hCA II with K(I)s in the range of 13-278nM, and
      hCA IX with K(I)s in the range of 0.12-549nM. The first hCA IX-selective
      inhibitors were thus detected, as the chlorotriazinyl-sulfanilamide and the bis
      ethoxytriazinyl derivatives of sulfanilamide/homosulfanilamide showed selectivity
      ratios for CA IX over CA II inhibition in the range of 166-706. Furthermore, some
      of these compounds have subnanomolar affinity for hCA IX, with K(I)s in the range
      0.12-0.34nM. These derivatives are interesting candidates for the development of
      novel unconventional anticancer strategies targeting the hypoxic areas of tumors.
      Clear renal cell carcinoma, which is the most lethal urologic malignancy and is
      both characterized by very high CA IX expression and chemotherapy
      unresponsiveness, could be the leading candidate of such novel therapies.

PMID- 15454240
TI  - Carbonic anhydrase inhibitors. Inhibition of the newly isolated murine isozyme
      XIII with anions.
AB  - The inhibition of the newly discovered cytosolic carbonic anhydrase (CA, EC
      4.2.1.1) isozyme XIII of murine origin (mCA XIII) has been investigated with a
      series of anions, such as the physiological ones (bicarbonate, chloride), or the
      metal complexing anions (cyanate, cyanide, azide, hydrogen sulfide, etc),
      nitrate, nitrite, sulfate, sulfamate, sulfamide as well as with phenylboronic and
      phenylarsonic acids. The best mCA XIII inhibitors were cyanate, thiocyanate,
      cyanide and sulfamide, with K(I)-s in the range of 0.25microM-0.74 mM, whereas
      fluoride, iodide, azide, carbonate and hydrogen sulfide were less effective (K(I)
      s in the range of 3.0-5.5mM). The least effective inhibitors were sulfate,
      chloride and bicarbonate (K(I)-s in the range of 138-267 mM). The affinity of mCA
      XIII for anions is very different from that of the other cytosolic isozymes (hCA
      I and II) or the mitochondrial isozyme hCA V. This resistance to inhibition by
      the physiological anions bicarbonate and chloride suggests an evolutionary
      adaptation of CA XIII to the presence of high concentrations of such anions
      (e.g., in the reproductive tract of both female and male), and the possible
      participation of this isozyme (similarly to CA II, CA IV and CA V) in metabolons
      with proteins involved in the anion exchange and transport, such as the anion
      exchangers (AE1-3) or the sodium bicarbonate co-transporter (NBC1 and NBC3)
      proteins, which remain to be identified.

PMID- 15454241
TI  - New N-pyridinyl(methyl)-indolalkanamides acting as topical inflammation
      inhibitors.
AB  - The authors have described the synthetic way to new N
      pyridinyl(methyl)indolylpropanamides acting as non acidic NSAIDs.
      Pharmacomodulation was carried out at N-1 and C-5 of the indole ring and at the
      level of the propanamide chain. N-(pyridin-3-ylmethyl)-3-[5-chloro-1-(4
      chlorobenzyl)-indol-3-yl]propanamide 32 represents one of the most potent
      compounds evaluated in the TPA-induced mouse ear swelling assay, with a level of
      activity higher than that of ibuprofen and comparable to that of dexamethasone.

PMID- 15454242
TI  - Identification of 2,3-diaryl-pyrazolo[1,5-b]pyridazines as potent and selective
      cyclooxygenase-2 inhibitors.
AB  - GW406381 (8), currently undergoing clinical evaluation for the treatment of
      inflammatory pain is a member of a novel series of 2,3-diaryl-pyrazolo[1,5
      b]pyridazine based cyclooxygenase-2 (COX-2) inhibitors, which have been shown to
      be highly potent and selective. Several examples of the series, in addition to
      possessing favourable pharmacokinetic profiles and analgesic activity in vivo,
      have also demonstrated relatively high brain penetration in the rat compared with
      the clinically available compounds, which may ultimately prove beneficial in the
      treatment of pain.

PMID- 15454243
TI  - Early mortality rates: a tool for phase III trials or for changing standard
      practice?

PMID- 15454244
TI  - A new international framework for palliative care.
AB  - In spite of recent advances in anti-cancer treatments, most adult cancer patients
      still ultimately die from their disease. There should therefore be free access to
      palliative care around the clock and seven days a week, for all cancer patients,
      as a fundamental human right. At present, the implementation of palliative care
      and patients' access to it are inconsistent across Europe and many other parts of
      the world. The World Health Organisation (WHO) made an important advance in 1986
      by first defining palliative care and, then updating this definition in 2002.
      However, this definition could benefit from further refinement in order to
      reflect the increasing multi-professional specialisation in this subject, and to
      recognise the different models for delivering this type of care. We recommend
      that palliative care should be defined as follows: Palliative care is the person
      centred attention to symptoms, psychological, social and existential distress in
      patients with limited prognosis, in order to optimise the quality of life of
      patients and their families or close friends. Based on this definition, we
      propose two further types of palliative care which reflect the reality of how
      palliative care is actually delivered: Basic palliative care is the standard of
      palliative care which should be provided by all healthcare professionals, in
      primary or secondary care, within their normal duties to patients with life
      limiting disease. Specialised palliative care is a higher standard of palliative
      care provided at the expert level, by a trained multi-professional team, who must
      continually update their skills and knowledge, in order to manage persisting and
      more complex problems and to provide specialised educational and practical
      resources to other non-specialised members of the primary or secondary care
      teams. If a patient has difficult symptoms which cannot be controlled by his/her
      current healthcare team, he/she has a right to be referred, and the current
      healthcare provider has an obligation to refer, to the local palliative care
      team. Important priorities to ensure the standardisation of, and uniform access
      to, palliative care for all cancer patients include: Integration of palliative
      care services with the primary care and oncology teams. Establishment of a
      specialised palliative care service in each major cancer centre. Establishment of
      educational programmes covering palliative care for undergraduates, oncologists,
      primary care team members and specialists training in palliative care. Support
      for research using appropriate methodologies to underpin the scientific basis of
      palliative care. Establishment of quality assurance programmes. Recognition of
      palliative medicine as a medical specialty. Establishment of academic centres of
      excellence with chairs of palliative medicine and palliative care nursing.
      Removal of unnecessary restrictions on all drugs which are proven to be of
      benefit in symptom control, especially improving access to strong opioids.
      Improved information for patients and family carers to allow them to make choices
      and exercise autonomy.

PMID- 15454245
TI  - EORTC guidelines for the use of erythropoietic proteins in anaemic patients with
      cancer.
AB  - Anaemia is frequently diagnosed in patients with cancer, yet it is difficult to
      identify a single cause due to its multifactorial aetiology. We conducted a
      systematic literature review (1996-2003) to produce evidence-based guidelines on
      the use of erythropoietic proteins in anaemic patients with cancer (see ). Level
      I evidence exists for a positive impact of erythropoietic proteins on haemoglobin
      (Hb) levels when administered to patients with chemotherapy-induced anaemia or
      anaemia of chronic disease, when used to prevent cancer anaemia, in patients
      undergoing cancer surgery and following allogeneic bone marrow transplantation.
      The Hb level at which erythropoietic protein therapy should be initiated is
      difficult to determine as it varied between studies; a large number of Level I
      studies in patients with chemotherapy-induced anaemia or anaemia of chronic
      disease enrolled patients with a Hb concentration </=105 g/L, but none compared
      the effect of different baseline Hb levels on the response to treatment.
      Similarly, several studies defined the target Hb concentration as 120-130 g/L
      following treatment with erythropoietic proteins, but none specifically addressed
      the correlation between target Hb level and clinical benefit in a randomised
      fashion. Level I evidence shows that red blood cell (RBC) transfusion
      requirements are significantly reduced with erythropoietic protein therapy in
      patients with chemotherapy-induced anaemia or when used to prevent cancer anaemia
      (approximately 20% reduction compared with controls). We found indirect Level I
      and III evidence that patients with chemotherapy-induced anaemia or anaemia of
      chronic disease initially classified as non-responders to standard doses proceed
      to respond to treatment following a dose increase (absolute increases in response
      rate ranged from 8% to 18%). However, none of these studies examined the effect
      on response rates of a longer treatment period at the lower dose, or performed a
      randomised comparison of a dose increase versus an unchanged dose. There is Level
      I evidence to show that quality-of-life (QOL) is significantly improved in
      patients with chemotherapy-induced anaemia and in those with anaemia of chronic
      disease, particularly in patients achieving a Hb response to erythropoietic
      protein therapy. There are insufficient data to determine the effect on survival
      following treatment with erythropoietic proteins in conjunction with chemotherapy
      or radiotherapy. There is Level I evidence that dosing of erythropoietic proteins
      less frequently than three times per week (TIW) is efficacious when used to treat
      chemotherapy-induced anaemia or prevent cancer anaemia. There is Level III
      evidence that initial doses of erythropoietic proteins considered to be higher
      than current standard practice produce higher haematological responses in
      patients with chemotherapy-induced anaemia or anaemia of chronic disease. Level I
      evidence demonstrates that several baseline patient parameters (e.g., low
      endogenous erythropoietin [EPO] concentration, age <60 years, Hb concentration
      >/=90 g/L) impact upon the response to erythropoietic proteins when used to treat
      chemotherapy-induced anaemia or prevent cancer anaemia. Evidence indicates that
      endogenous EPO concentration impacts on response in patients with
      lymphoproliferative malignancies, but is not a valid parameter in patients with
      solid tumours. There is Level I evidence that fixed doses of erythropoietic
      proteins can be used at the start of therapy to treat patients with chemotherapy
      induced anaemia, but maintenance doses should be titrated individually. There is
      no evidence that pure red cell aplasia (PRCA) occurs following treatment with
      erythropoietic proteins in patients with chemotherapy-induced anaemia or when
      used prophylactically in patients with cancer. There is Level I evidence that the
      risk of thromboembolic events and hypertension are slightly elevated in patients
      with chemotherapy-induced anaemia receiving erythropoietic proteins. Level I
      evidence supports the effectiveness of erythropoietic proteins to prevenroteins
      to prevent anaemia in non-anaemic cancer patients receiving chemotherapy or
      radiotherapy or in those undergoing cancer surgery. However, these are non
      licensed indications and we do not currently recommend the prophylactic use of
      erythropoietic proteins to prevent anaemia in patients who have normal Hb values
      at the start of treatment. Additional trials are warranted, especially on the
      issues of iron replacement and cost-effectiveness of erythropoietic protein
      therapy, as well as on tumour response/progression and survival.

PMID- 15454246
TI  - The ubiquitin-mediated protein degradation pathway in cancer: therapeutic
      implications.
AB  - The highly conserved eukaryotic ubiquitin-proteasome system (UP-S) plays a
      pivotal role in protein homeostasis and is critical in regulating normal and
      cancer-related cellular processes. The hierarchical nature of the UP-S provides a
      rich source of molecular targets for specific intervention and has therefore
      arisen as a promising approach to innovative anticancer therapies. The first in
      class proteasome inhibitory agent Bortezomib (Velcade) has recently obtained
      regulatory approval for the treatment of multiple myeloma. Ubiquitin-mediated
      degradation is a complex process that is comprised of well defined steps
      involving ubiquitin-activating enzymes (E1s), ubiquitin-conjugating enzymes (E2s)
      and ubiquitin ligases (E3s). Although a single E1 activates the ubiquitin
      conjugation machinery, a large number of E2 conjugating enzymes and E3 ligases
      are now known to exist. Proteins tagged with ubiquitin are subsequently
      recognised by the proteasome for digestion and fragmentation. The enzymatic
      nature, multitude of E3s and their specific substrate recognition predestines
      them as therapeutic targets. This article will review known inhibitors of the
      proteasome and their molecular mechanisms as well as ongoing developments and
      promising avenues for targeting substrate-specific E3 ligases that are likely to
      yield a new class of therapeutics that will serve and complement the
      armamentarium of anticancer drugs.

PMID- 15454247
TI  - Sixty-day all-cause mortality rates in patients treated for gastrointestinal
      cancers, in randomised trials, at the Royal Marsden Hospital.
AB  - The aim of this study was to determine the 60-day all-cause mortality rate,
      during chemotherapy, for patients with oesophagogastric, pancreatic, and
      colorectal cancer. We analysed 1720 patients that were treated within randomised
      trials. The minimum follow-up period was > 60 days. Sixty-day mortality and 95%
      Confidence Intervals (CI) were calculated from the Kaplan-Meier survival curves.
      Causes of death were classified as treatment-related, disease-related or vascular
      syndrome-induced deaths. Patients with oesophagogastric cancer that could not
      tolerate a cis-platinum-containing regimens were treated with infused 5
      fluorouracil (5FU)+/-mitomycin-C (MMC). The 60-day mortality rate depends upon
      the site of the primary tumour and the disease status (adjuvant versus advanced).
      The rate of treatment- and vascular syndrome-induced deaths was </=1.8%. For
      patients with advanced disease, most of the early deaths were disease-related. In
      adjuvant colorectal cancer, one patient died within 60 days (myocardial
      infarction). This study provides a benchmark for assessing the safety of regimens
      used in these disease settings.

PMID- 15454248
TI  - Change in histological grade in locally recurrent soft tissue sarcomas.
AB  - Histological examination of locally recurrent soft tissue sarcomas usually
      reveals an appearance similar to that of the original tumour. Occasionally,
      however, recurrent sarcomas appear more or less malignant histologically than the
      initial lesion. The goals of this paper were to identify the frequency with which
      this phenomenon occurs, factors that predict for a change in grade and to
      determine if this change is associated with a different prognosis from other
      patients with local recurrence. From a large sarcoma database, 124 patients with
      local recurrence were identified. These patients were distributed into groups who
      had no change in histological grade, increased histological grade or decreased
      histological grade on local recurrence. Increased grade occurred approximately
      20% of the time, whereas decreased grade occurred in 7% of cases. A histological
      diagnosis of myxofibrosarcoma was predictive of an increase in histological grade
      on local recurrence. An increase in histological grade with local recurrence was
      not associated with a poorer survival.

PMID- 15454249
TI  - French version of FACT-G: validation and comparison with other cancer-specific
      instruments.
AB  - The aim of this study was to assess the validity of the French version of the
      Functional Assessment of Cancer Therapy - General (FACT-G), and to compare its
      psychometric properties with those of two other cancer-specific quality of life
      questionnaires, European Organisation for Research and Treatment of Cancer
      Quality of Life - Core 30 (EORTC QLQ-C30) and Functional Living Index - Cancer
      (FLIC). Two hundred and twenty three patients with breast or colorectal cancer
      completed the FACT-G questionnaire in French followed by (in random order) the
      QLQ-C30 and FLIC. An additional 87 patients with head and neck (H&N) cancer
      completed the FACT-H&N followed by the QLQ-C30 and H&N-Besancon. The French
      version of FACT-G was internally consistent, and its reproducibility was
      excellent. FACT-G Physical Well-Being and global scores correlated with all QLQ
      C30 subscales. There was evidence of discriminant validity. Compared with the
      other tools, FACT-G included a statistically significantly higher proportion of
      items patients considered to be confusing or upsetting. Patients with breast or
      colorectal cancer expressed a preference for QLQ-C30. Use of the specific H&N
      additional items increased the responsiveness to change of FACT-G. The French
      version of FACT-G is valid and has psychometric properties similar to those of
      FLIC and QLQ-C30.

PMID- 15454250
TI  - Risk factors for catheter-related thrombosis in cancer patients.
AB  - We investigated the risk factors for venous thrombosis in cancer patients with
      implantable ports undergoing chemotherapy. One hundred and seventy one ports were
      placed in a central ("chest ports") and 84 in a peripheral vein ("arm ports"),
      181 received prophylactic nadroparin and 10 coumarin. Clinically overt thrombosis
      was confirmed by ultrasound or angiography. Catheter-related thrombosis incidence
      without anticoagulants was 28% in arm and 33% in chest ports, but with
      anticoagulants this was 32% in arm and only 1% in chest ports (odds ratio (OR)
      34.8 95% confidence interval (CI) 7.3-165). Left-sided placement compared with
      right-sided and catheter tip position in the superior vena cava compared with
      right atrium were associated with a 3.5 respectively 2.6-fold increased risk.
      Thrombosis was associated with elevated homocysteine levels (OR=3.8, 95% CI 1.3
      11.3), but not with factor V Leiden or prothrombin 20210A gene mutations, or high
      concentration of factor VIII, IX or XI. Prophylaxis with anticoagulants is
      recommended for chest, but not for arm ports. Determination of plasma
      homocysteine levels may identify patients at an increased risk for thrombosis.

PMID- 15454251
TI  - Clinical and psychometric validation of a questionnaire module, the EORTC QLQ-STO
      22, to assess quality of life in patients with gastric cancer.
AB  - The purpose of this study was to define the measurement properties and clinical
      validity of the European Organisation for Research and Treatment of Cancer
      (EORTC) questionnaire module to assess health-related quality of life (HRQL) in
      gastric cancer. The EORTC gastric cancer module, QLQ-STO 22, was administered
      with the QLQ-C30, core questionnaire, to 219 patients undergoing treatment with
      curative or palliative intent before and after treatment. Reliability and
      validity of the module was tested and patients' debriefing comments analysed.
      Compliance rates were high, questionnaires well accepted and less than 4% of
      items had missing data. Multi-trait scaling analyses and face validity refined
      the module to five scales and four single items. Scales distinguished between
      clinically distinct groups of patients and demonstrated treatment-induced changes
      over time. Test-retest scores demonstrated good reliability. The EORTC QLQ-STO 22
      demonstrates psychometric and clinical validity that supports its use to
      supplement the EORTC QLQ-C30 to assess quality of life in patients with gastric
      cancer undergoing surgery, surgery and chemoradiotherapy, palliative
      chemotherapy, palliative surgery and best supportive care.

PMID- 15454252
TI  - Protein kinase C alpha expression in normal breast, ductal carcinoma in situ and
      invasive ductal carcinoma.
AB  - The purpose of this study was to determine if Protein Kinase C alpha (PKC alpha)
      is altered in expression or localisation in normal breast, ductal carcinoma in
      situ (DCIS) and invasive ductal carcinoma (IDC). We obtained 14 mixed cases of
      invasive ductal carcinoma (IDC) and DCIS, 36 pure DCIS cases and 25 cases of
      normal breast. The sections were stained immunohistochemically for PKC alpha
      expression. Staining was cytoplasmic. The results showed a progressive reduction
      in staining intensity from normal breast to invasive ductal carcinoma. The
      staining pattern was heterogeneous in the cytoplasm of DCIS and IDC, but
      homogeneous in the cytoplasm of normal breast ductal epithelium. Interestingly,
      mitotic cells and cells with aberrant nuclear morphology showed increased
      cytoplasmic staining in DCIS and IDC. PKC alpha activity is altered in dividing
      or abnormal cells, but overall expression is reduced in IDC. This raises the
      possibility of an alteration in the subcellular localisation of PKC alpha which
      may relate to changes in desmosomal adhesive state.

PMID- 15454253
TI  - Phase II study of high-dose cyclophosphamide in relapsing and/or resistant
      hepatoblastoma in children: a study from the SIOPEL group.
AB  - The study sought to evaluate the response to cyclophosphamide (CPM) in
      hepatoblastoma (HB). Patients with a refractory or relapsing HB after first-line
      therapy as per SIOPEL 2 and 3 protocols were eligible. All patients were to
      receive two courses of CPM 2 g/m(2) on days 1 and 2 at 3-week intervals. Eighteen
      patients were included; 17 were evaluable for response. Prior treatment was
      cisplatinum alone (1 patient) or cisplatinum-carboplatin-doxorubicin (17
      patients). The disease status at the beginning of CPM was: progressive during
      first-line treatment (10 patients), persistent unresectable disease at the end of
      the protocol (2 patients), relapse (6 patients). Tumour response was partial
      response (1 patient), stable disease (1 patient), progressive disease (15
      patients) and not evaluable in one. All patients died, 17 of progressive disease
      and one of surgery complications. The low response rate (1/17) led the SIOPEL
      group to conclude that single-agent CPM is not effective for the treatment of
      relapsing or refractory HB.

PMID- 15454254
TI  - Symptom interval in young people with bone cancer.
AB  - Symptom interval (SI), the time from first symptom/sign to diagnosis and
      initiation of treatment, appears to be principally influenced by tumour biology.
      Whether the age of the patient, patient delay, professional delay and access to
      health professionals influences the SI in bone tumours was investigated in this
      study. 115 patients with newly diagnosed osteosarcoma and Ewing's sarcoma were
      retrospectively reviewed. The median total SI for all bone tumours was 3.8 months
      (range 1-46 months). Patients older than 12 years had a longer SI (P = 0.05) and
      more patient delays (P = 0.02). Total SI and professional delays were longer if
      the General Practitioner was first seen compared with an Accident and Emergency
      Consultant (P = 0.02 and 0.02, respectively). However, SI did not influence
      overall and event-free survival in this series. Bone tumour patients have long
      SIs that are significantly affected by age and local health-care support systems.
      Early referral to specialists would help to alleviate anxiety and distress to the
      patient and family, even if currently delay does not influence outcome.

PMID- 15454255
TI  - Methotrexate inhibits the glyoxalase system in vivo in children with acute
      lymphoid leukaemia.
AB  - The inhibition of glyoxalase I leads to antitumour activity through the
      accumulation of methylglyoxal. Our earlier observations suggested that
      methotrexate (MTX) may affect the glyoxalase system. This prompted a serial study
      of the drug on this metabolic pathway. Ten children with acute lymphoid leukaemia
      (ALL), admitted to our department between January 2002 and July 2003, were
      enrolled. Plasma D-lactate was assayed before, 24 and 72 h after the start of
      four consecutive MTX infusions (5 g/m(2)/24 h) in each patient. Inhibition of
      glyoxalase I was tested in vitro, using human erythrocyte lysates and yeast
      enzyme. The elevated initial plasma D-lactate levels (P<0.02) fell significantly
      (P<0.001) in response to 24 h MTX infusions. In vitro, MTX, folic and folinic
      acids inhibited the activity of glyoxalase I. Thus, MTX seems to affect the alpha
      oxoaldehyde metabolism in vivo, as a likely consequence of glyoxalase I
      inhibition. This action probably contributes to the anticancer activity and
      toxicity of the drug.

PMID- 15454256
TI  - The European Cancer Anaemia Survey (ECAS): a large, multinational, prospective
      survey defining the prevalence, incidence, and treatment of anaemia in cancer
      patients.
AB  - The European Cancer Anaemia Survey (ECAS) was conducted to prospectively evaluate
      the prevalence, incidence and treatment of anaemia (haemoglobin <12.0 g/dL) in
      European cancer patients, including the relationship of mild, moderate and severe
      anaemia to performance status. Patients were evaluated for up to 6 months. Data
      (N=15367) included demographics, tumour type, performance status, haemoglobin
      levels, cancer treatments and anaemia treatments. Prevalence of anaemia at
      enrollment was 39.3% (haemoglobin <10.0 g/dL, 10%), and 67.0% during the survey
      (haemoglobin <10.0 g/dL, 39.3%). Low haemoglobin levels correlated significantly
      with poor performance status. Incidence of anaemia was 53.7% (haemoglobin <10.0
      g/dL, 15.2%). Anaemia was treated in 38.9% of patients (epoetin, 17.4%;
      transfusion, 14.9%; and iron, 6.5%). Mean haemoglobin to initiate anaemia
      treatment was 9.7 g/dL. Anaemia prevalence and incidence in cancer patients are
      high. Anaemia significantly correlates with poor performance status and many
      anaemic patients are not treated.

PMID- 15454257
TI  - Standard cancer patient population for age standardising survival ratios.
AB  - Standard adult cancer patients populations are derived in this paper as a tool
      for the calculation of age-standardised cancer survival figures. Previously used
      standards in survival analysis have been site- and/or study-specific. Here,
      multivariate methods have been used to define the smallest possible number of
      general standard cancer patient populations which are simple to use and provide
      standardised survival values close to the raw ones for the largest possible
      number of cancer sites. The analysis was based on data for over 1.1 million
      cancer patients included in the EUROCARE-2 study. The proposed standard
      populations consist of three age distributions, appropriate for cancers with
      incidence patterns: (1) increasing with age - the vast majority of cancers; (2)
      broadly constant with age and (3) mainly affecting young adults. The three
      standard distributions are presented by both broad and five-year age classes. The
      latter can be used to determine which of the three standards would be used for
      sites not included in the cluster analysis because their survival is generally
      calculated in unusual age groups. Overall, standard 1 is appropriate for over 91%
      of cases, standard 2 for just over 7%, and standard 3 for less than 2%. The
      proposed standards were tested on European (EUROCARE-2 and EUROCARE-3) and US
      (Surveillance, Epidemiology and End Results Program, SEER) relative survival
      data. There was very good correspondence between the raw (population weighted)
      and age-standardised survival figures.

PMID- 15454258
TI  - An alternative approach to age adjustment of cancer survival rates.
AB  - The measures of cancer prognosis most commonly reported by cancer registries are
      5- or 10-year absolute or relative survival rates. Because cancer survival rates
      often vary by the age of cancer patients, and because the age structure of cancer
      patients often varies between populations, age adjustment is crucial for
      comparative analyses of cancer survival rates. However, traditional age
      adjustment often breaks down for long-term survival rates, particularly for
      sparse data, and it may provide inconsistent results for relative survival rates,
      even if age adjustment is made to the study population's own age distribution. In
      this manuscript, we propose an alternative approach to age adjustment of both
      absolute and relative survival rates to overcome both the practical and
      conceptual problems inherent in traditional age adjustment. We outline the
      computational realisation of this approach, and we give an empirical illustration
      of its application using data from the nationwide Finnish Cancer Registry.

PMID- 15454259
TI  - Galectin-3 - an emerging prognostic indicator in advanced head and neck
      carcinoma.
AB  - Galectin-3, is a multifunctional effector. It is the only chimera-type member of
      the galectin family of endogenous lectins, which share specificity with beta
      galactosides and have a jelly-roll-like folding pattern. It's activity profile
      includes modulation of cell-cell and cell-extracellular matrix interactions and
      the regulation of proliferation and apoptosis/anoikis. While lectin
      histochemistry with plant/invertebrate proteins is routine practice and
      immunohistochemical analysis of endogenous lectins has been thoroughly examined,
      the application of an endogenous lectin as a marker is presently primarily a
      promising concept. The aims of our study were to test galectin-3 as a technical
      probe and to correlate staining by the tissue lectin, localising accessible
      ligands in situ, to clinicopathological characteristics and the prognosis of
      patients (relapse-free and overall survival) in advanced head and neck squamous
      cell cancer. We measured galectin-3-dependent staining in 53 surgically resected
      oropharyngeal and laryngeal cancer specimens (stage III or IV). Patients were
      divided into two groups based on a threshold of 5% positivity in the tumour cell
      population. The patient's degree of positivity was significantly correlated with
      their level of differentiation and keratinisation and lack of lymph node
      involvement (P=0.0001, P=0.0007 and P=0.0224, respectively). Periods of relapse
      free and overall survival were significantly shortened when the tumour population
      failed to meet the positivity criterion, i.e. to harbour ligands for the
      endogenous lectin (P=0.0039 and P=0.0259, respectively). We conclude that (a)
      studies with an endogenous lectin as a marker are technically feasible and (b)
      detection of accessible galectin-3-specific ligands is an independent prognostic
      marker in advanced head and neck squamous cell cancer with therapeutic potential.
      Of note, histochemical application of an endogenous effector after its
      purification and labelling may bear relevance beyond the galectins.

PMID- 15454260
TI  - Stage-specific inhibition of mammary carcinogenesis by 1alpha-hydroxyvitamin D5.
AB  - Active metabolites of vitamin D are well recognised as cancer chemopreventive and
      chemotherapeutic agents. However, they are toxic at effective concentrations.
      Earlier, we reported that a non-toxic analogue of vitamin D, 1alpha
      hydroxyvitamin D5(1alpha(OH)D5), inhibited carcinogen-induced mammary lesion
      formation in mouse mammary organ cultures (MMOC) and in N-methyl-N-nitrosourea
      (MNU)-induced rat mammary carcinogenesis. In the present study, we determined if
      1alpha (OH)D5 action is selective during the initiation or promotion phases in
      MMOC and in vivo. In MMOC, 1 microM 1alpha (OH)D5 suppressed both ovarian hormone
      dependent and -independent mammary lesions by more than 60%. Inhibition of
      alveolar lesions was observed only during the promotion stage (p=0.0016). In a
      7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinogenesis experiment,
      1alpha (OH)D5 (40 microg/kg diet) inhibited cancer incidence by 37.5% (p<0.05) if
      1alpha (OH)D5 was present in food during the promotion phase (+1 to end).
      However, a D5-supplemented diet during the initiation phase (-2 to +1 week) did
      not provide any protection. These results clearly show, for the first time, that
      the effects of vitamin D may be mediated selectively during the promotion or
      progression phases of carcinogenesis.

PMID- 15454261
TI  - Titin isoform changes in rat myocardium during development.
AB  - Developmental changes in the alternative splicing patterns of titin were observed
      in rat cardiac muscle. Titin from 16-day fetal hearts consisted of a single 3710
      kDa band on SDS agarose gels, and it disappeared by 10 days after birth. The
      major adult N2B isoform (2990 kDa) first appeared in 18-day fetal hearts and its
      proportion in the ventricle increased to approximately 85% from 20 days of age
      and older. Changes in three other intermediate-sized N2BA isoform bands also
      occurred during this same time period. The cDNA sequences of fetal cardiac, adult
      ventricle, and adult soleus were different in the PEVK and alternatively spliced
      middle Ig domain. Extensive heterogeneity in splice patterns was found in the
      N2BA PEVK region. The extra length of the fetal titin isoforms appeared to be due
      to both a greater number of middle Ig domains expressed plus the inclusion of
      more PEVK exons. Passive tension measurements on myocyte-sized fragments
      indicated a significantly lower tension in neonate versus adult ventricles at
      sarcomere lengths greater than 2.1 microm, consistent with the protein and cDNA
      sequence results. The time course of the titin isoform switching was similar to
      that occurring with myosin and troponin I during development.

PMID- 15454262
TI  - Pax9 is required for filiform papilla development and suppresses skin-specific
      differentiation of the mammalian tongue epithelium.
AB  - The epidermis is a derivative of the surface ectoderm. It forms a protective
      barrier and specific appendages including hair, nails, and different eccrine
      glands. The surface ectoderm also forms the epithelium of the oral cavity and
      tongue, which develop a slightly different barrier and form different appendages
      such as teeth, filiform papillae, taste papillae, and salivary glands. How this
      region-specific differentiation is genetically controlled is largely unknown. We
      show here that Pax9, which is expressed in the epithelium of the tongue but not
      in skin, regulates several aspects of tongue-specific epithelial differentiation.
      In Pax9-deficient mice filiform papillae lack the anterior-posterior polarity, a
      defect that is associated with temporal-spatial changes in Hoxc13 expression.
      Barrier formation is disturbed in the mutant tongue and genome-wide expression
      profiling revealed that the expression of specific keratins (Krt), keratin
      associated proteins, and members of the epidermal differentiation complex is
      significantly down-regulated. In situ hybridization demonstrated that several
      'hard' keratins, Krt1-5, Krt1-24, and Krt2-16, are not expressed in the absence
      of Pax9. Notably, specific 'soft' keratins, Krt2-1 and Krt2-17, normally weakly
      expressed in the tongue but present at high levels in skin and in
      orthokeratinized oral dysplasia are up-regulated in the mutant tongue epithelium.
      This result indicates a partial trans-differentiation to an epithelium with skin
      specific characteristics. Together, our findings show that Pax9 regulates
      appendage formation in the mammalian tongue and identify Pax9 as an important
      factor for the region-specific differentiation of the surface ectoderm.

PMID- 15454263
TI  - Abdominal-B is essential for proper sexually dimorphic development of the
      Drosophila gonad.
AB  - Sexual dimorphism requires the integration of positional information in the
      embryo with the sex determination pathway. Homeotic genes are a major source of
      positional information responsible for patterning along the anterior-posterior
      axis in embryonic development, and are likely to play a critical role in sexual
      dimorphism. Here, we investigate the role of homeotic genes in the sexually
      dimorphic development of the gonad in Drosophila. We have found that Abdominal-B
      (ABD-B) is expressed in a sexually dimorphic manner in the embryonic gonad.
      Furthermore, Abd-B is necessary and sufficient for specification of a sexually
      dimorphic cell type, the male-specific somatic gonadal precursors (msSGPs). In
      Abd-B mutants, the msSGPs are not specified and male gonads now resemble female
      gonads with respect to these cells. Ectopic expression of Abd-B is sufficient to
      induce formation of extra msSGPs in additional segments of the embryo. Abd-B
      works together with abdominal-A to pattern the non-sexually dimorphic somatic
      gonad in both sexes, while Abd-B alone specifies the msSGPs. Our results indicate
      that Abd-B acts at multiple levels to regulate gonad development and that Abd-B
      class homeotic genes are conserved factors in establishing gonad sexual
      dimorphism in diverse species.

PMID- 15454264
TI  - Myosin VI plays a role in cell-cell adhesion during epithelial morphogenesis.
AB  - Myosin VI is an unconventional Myosin that has been implicated in vesicle
      transport and membrane trafficking. We isolated lethal mutants of Myosin VI,
      which lack protein once maternal supplies have been utilised during
      embryogenesis. Dorsal closure, where there is a ring of Myosin VI at the edge of
      the migrating epithelial sheet, is often abnormal. The sheet of migrating cells
      is irregular, rather than a smooth epithelium and cells begin to detach. Some
      embryos hatch into larvae, containing detached cells loose in the haemolymph.
      Myosin VI is crucial for correct cell morphology and maintenance of adhesive
      cellular contacts within epithelial cell layers.

PMID- 15454265
TI  - Melanophore sublineage-specific requirement for zebrafish touchtone during neural
      crest development.
AB  - The specification, differentiation and maintenance of diverse cell types are of
      central importance to the development of multicellular organisms. The neural
      crest of vertebrate animals gives rise to many derivatives, including pigment
      cells, peripheral neurons, glia and elements of the craniofacial skeleton. The
      development of neural crest-derived pigment cells has been studied extensively to
      elucidate mechanisms involved in cell fate specification, differentiation,
      migration and survival. This analysis has been advanced considerably by the
      availability of large numbers of mouse and, more recently, zebrafish mutants with
      defects in pigment cell development. We have identified the zebrafish mutant
      touchtone (tct), which is characterized by the selective absence of most neural
      crest-derived melanophores. We find that although wild-type numbers of
      melanophore precursors are generated in the first day of development and migrate
      normally in tct mutants, most differentiated melanophores subsequently fail to
      appear. We demonstrate that the failure in melanophore differentiation in tct
      mutant embryos is due at least in part to the death of melanoblasts and that tct
      function is required cell autonomously by melanoblasts. The tct locus is located
      on chromosome 18 in a genomic region apparently devoid of genes known to be
      involved in melanophore development. Thus, zebrafish tct may represent a novel as
      well as selective regulator of melanoblast development within the neural crest
      lineage. Further, our results suggest that, like other neural crest-derived
      sublineages, melanogenic precursors constitute a heterogeneous population with
      respect to genetic requirements for development.

PMID- 15454266
TI  - Touchtone promotes survival of embryonic melanophores in zebrafish.
AB  - An outstanding problem in the study of vertebrate development is the
      identification of the genes that direct neural crest precursor cells to adopt and
      maintain specific differentiated cell fates. In an effort to identify such genes,
      we have carried out a mutagenesis screen in zebrafish and isolated mutants that
      lack neural crest-derived melanophores. In this manuscript we describe the
      phenotype of one such mutant, touchtone(b722) (tct), and the map position of the
      gene it defines. Analysis of expression of dopachrome tautomerase (dct) and
      microphthalmia (mitfa) suggests that melanophore precursors are specified
      normally in homozygous tct mutants. However, differentiated melanophores are
      pale, small, and about half of them have disappeared by 48 h of development,
      apparently by cell death. We show that melanophores require Tct function cell
      autonomously. Signals from the receptor tyrosine kinase receptor C-kit are
      essential for survival of melanophores in zebrafish and mammals. However,
      differences in the phenotypes of tct and c-kit homozygous mutants, and an absence
      of interaction between c-kit and tct heterozygotes, suggest that Tct functions
      independently of the C-kit pathway. Other neural crest derivatives, including
      other pigment cell types, appear normal in tct mutants. Interestingly, tct mutant
      embryos undergo a temporary period of near complete paralyzis during the second
      day of development, although markers of axons of motor and sensory neurons look
      normal in this period. A fraction of tct(b722) mutants survive to adulthood, but
      mutant adults are small, indicating a role for Tct in post-larval growth. The tct
      gene maps to a small interval near a telomere of chromosome 18. Thus, we have
      identified a zebrafish gene that when mutated produces semi-viable offspring and
      that may serve as a model of human diseases that have both pigmentation and
      neurological symptoms.

PMID- 15454267
TI  - Drosophila non-muscle alpha-actinin is localized in nurse cell actin bundles and
      ring canals, but is not required for fertility.
AB  - The single copy Drosophila alpha-actinin gene is alternatively spliced to
      generate three different isoforms that are expressed in larval muscle, adult
      muscle and non-muscle cells, respectively. We have generated novel alpha-actinin
      alleles, which specifically remove the non-muscle isoform. Homozygous mutant
      flies are viable and fertile with no obvious defects. Using a monoclonal antibody
      that recognizes all three splice variants, we compared alpha-actinin distribution
      in wild type and mutant embryos and ovaries. We found that non-muscle alpha
      actinin was present in young embryos and in the embryonic central nervous system.
      In ovaries, non-muscle alpha-actinin was localized in the nurse cell subcortical
      cytoskeleton, cytoplasmic actin cables and ring canals. In the mutant, alpha
      actinin expression remained in muscle tissues, but also in a subpopulation of
      epithelial cells in both embryos and ovaries. This suggests that various
      populations of non-muscle cells regulate alpha-actinin expression in different
      ways. We also show that ectopically expressed adult muscle-specific alpha-actinin
      localizes to all F-actin containing structures in the nurse cells in the absence
      of endogenous non-muscle alpha-actinin.

PMID- 15454268
TI  - Cellular mechanisms of sex determination in the red-eared slider turtle,
      Trachemys scripta.
AB  - In all vertebrates sex determination is the step at which development of a testis
      or ovary is initiated in the bipotential gonad. Although Mus musculus and the red
      eared slider turtle, Trachemys scripta, use different mechanisms to initiate
      organogenesis of the testis (the Y-linked gene, Sry, in the mouse vs. the
      incubation temperature of the egg in the turtle), the structure of the adult
      testis is strikingly similar. We have identified several cellular mechanisms
      involved in testis organogenesis in mouse. Here we investigated whether these
      cellular mechanisms are conserved in T. scripta downstream of the temperature
      dependent switch. Cell tracing experiments indicated that the coelomic epithelium
      in T. scripta contributes precursors for Sertoli cells and interstitial cells as
      in mouse. However, we detect no male-specific mesonephric cell migration, a
      process required for the de novo testis cord-forming process in mouse. In
      contrast to mouse gonads, where no cord structure is discernible until after the
      divergence of testis development, we find that primitive sex cords continuous
      with the coelomic epithelium exist in all T. scripta gonads from the earliest
      bipotential stages examined. We conclude that typical testis architecture results
      from the maintenance and elaboration of primitive sex cords in T. scripta rather
      than the assembly of de novo structures as in mouse.

PMID- 15454269
TI  - Asymmetric Nodal expression in the mouse is governed by the combinatorial
      activities of two distinct regulatory elements.
AB  - In all vertebrates, invariant left/right (L/R) positioning and organization of
      the internal viscera is controlled by a conserved pathway. Nodal, a member of the
      TGFbeta superfamily is a critical upstream component responsible for initiating
      L/R axis determination. Asymmetric Nodal expression in the node preceeds and
      foreshadows morphological L/R asymmetry. Here we address the mechanism of Nodal
      activation in the left LPM by studying the function of a novel enhancer element,
      the AIE. We show this element is exclusively active in cells of the left lateral
      plate mesoderm (LPM) and is not itself responding to Nodal asymmetry. To test the
      hypothesis that this element may initiate asymmetric Nodal expression in the LPM,
      we deleted it from the mouse germ line. Mice homozygous for the AIE deletion
      (Nodal(deltaaie/deltaaie)) show no defects. However, we find that the AIE
      contributes to regulating the level of asymmetric Nodal activity; analysis of
      transheterozygous embryos (Nodal(deltaaie/null)) shows reduced Nodal expression
      in the left LPM associated with a low penetrance of L/R defects. Our findings
      point to the existence of two independent pathways that control Nodal expression
      in the left LPM.

PMID- 15454270
TI  - Introduction to the serial review on paraoxonases, oxidative stress, and
      cardiovascular diseases.

PMID- 15454271
TI  - Paraoxonases 1, 2, and 3, oxidative stress, and macrophage foam cell formation
      during atherosclerosis development.
AB  - Paraoxonases PON1 and PON3, which are both associated in serum with HDL, protect
      the serum lipids from oxidation, probably as a result of their ability to
      hydrolyze specific oxidized lipids. The activity of HDL-associated PON1 seems to
      involve an activity (phospholipase A2-like activity, peroxidase-like activity,
      lactonase activity) which produces LPC. To study the possible role of PON1 in
      macrophage foam cell formation and atherogenesis we used macrophages from control
      mice, from PON1 knockout mice, and from PON1 transgenic mice. Furthermore, we
      analyzed PON1-treated macrophages and PON1-transfected cells to demonstrate the
      contribution of PON1 to the attenuation of macrophage cholesterol and oxidized
      lipid accumulation and foam cell formation. PON1 was shown to inhibit cholesterol
      influx [by reducing the formation of oxidized LDL (Ox-LDL), increasing the
      breakdown of specific oxidized lipids in Ox-LDL, and decreasing macrophage uptake
      of Ox-LDL]. PON1 also inhibits cholesterol biosynthesis and stimulates HDL
      mediated cholesterol efflux from macrophages. PON2 and PON3 protect against
      oxidative stress, with PON2 acting mainly at the cellular level. Whereas serum
      PON1 and PON3 were inactivated under oxidative stress, macrophage PON2 expression
      and activity were increased under oxidative stress, probably as a compensatory
      mechanism against oxidative stress. Intervention to increase the paraoxonases
      (cellular and humoral) by dietary or pharmacological means can reduce macrophage
      foam cell formation and attenuate atherosclerosis development.

PMID- 15454272
TI  - Paraoxonase 1 and atherosclerosis: is the gene or the protein more important?
AB  - The oxidation of low-density lipoprotein (LDL) is centrally involved in the
      initiation and progression of atherosclerosis. High-density lipoprotein (HDL)
      paraoxonase 1 (PON1) retards the oxidation of LDL and is a major
      antiatherosclerotic component of HDL. The PON1 gene contains a number of
      functional polymorphisms in both the coding and the promoter regions, which
      affect either the level or the substrate specificity of PON1. Genetic case
      control and prospective studies conducted to date have produced confusing
      results. Meta-analysis of these studies indicates no simple relationship between
      the PON1 polymorphisms and the presence of coronary heart disease (CHD). However,
      at the present moment in time, it seems that PON1 status, i.e., activity and/or
      concentration, is more closely related to CHD, and indeed, PON1 has shown to be
      an independent risk factor for CHD in a prospective study, compared to the
      genetic polymorphisms. PON1 levels can also be modulated by
      environmental?lifestyle and possibly pharmaceutical factors. Larger, better
      designed, preferably prospective studies are needed to determine further the
      association of PON1 genetic polymorphisms and status with CHD.

PMID- 15454273
TI  - Mass spectrometric methods for the determination of flavonoids in biological
      samples.
AB  - There is an ever-increasing interest in the biological effects of the
      bioflavonoids, members of the large group of plant polyphenols. Because of the
      aromatic character of these compounds, they have been analyzed by several
      chromatographic methods. In the case of high-performance liquid chromatography,
      they are readily detected by their ultraviolet absorbance or electrochemical
      properties. More evidence that the bioflavonoids undergo extensive metabolism
      during uptake from the gut and distribution around the body and in specific
      tissues is accumulating. In addition, free radical products at sites of
      inflammatory processes react with bioflavonoids and their metabolites, generating
      important new compounds of as yet unknown properties. For these reasons, careful
      examination of the chemical nature of bioflavonoids and their products in
      biological systems is absolutely required. Combination of mass spectrometry with
      the various chromatographic methods has proved to be highly successful in this
      regard. This review of the literature on the bioflavonoids is focused on the
      methods that are currently available for their qualitative and quantitative
      analysis by mass spectrometry and covers the period 2001-2003. Emphasis is placed
      on the description and value of existing methods, followed by an examination of
      emerging technologies.

PMID- 15454274
TI  - Dark chocolate consumption increases HDL cholesterol concentration and chocolate
      fatty acids may inhibit lipid peroxidation in healthy humans.
AB  - Cocoa powder is rich in polyphenols and, thus, may contribute to the reduction of
      lipid peroxidation. Our aim was to study the effects of long-term ingestion of
      chocolate, with differing amounts of polyphenols, on serum lipids and lipid
      peroxidation ex vivo and in vivo. We conducted a 3 week clinical supplementation
      trial of 45 nonsmoking, healthy volunteers. Participants consumed 75 g daily of
      either white chocolate (white chocolate, WC group), dark chocolate (dark
      chocolate, DC group), or dark chocolate enriched with cocoa polyphenols (high
      polyphenol chocolate, HPC group). In the DC and HPC groups, an increase in serum
      HDL cholesterol was observed (11.4% and 13.7%, respectively), whereas in the WC
      group there was a small decrease (-2.9%, p < 0.001). The concentration of serum
      LDL diene conjugates, a marker of lipid peroxidation in vivo, decreased 11.9% in
      all three study groups. No changes were seen in the total antioxidant capacity of
      plasma, in the oxidation susceptibility of serum lipids or VLDL + LDL, or in the
      concentration of plasma F2-isoprostanes or hydroxy fatty acids. Cocoa polyphenols
      may increase the concentration of HDL cholesterol, whereas chocolate fatty acids
      may modify the fatty acid composition of LDL and make it more resistant to
      oxidative damage.

PMID- 15454275
TI  - MnSOD antisense treatment and exercise-induced protection against arrhythmias.
AB  - Exercise provides protection against ischemia-reperfusion (I-R)-induced
      arrhythmias, myocardial stunning, and infarction. An exercise-induced increase in
      myocardial manganese superoxide dismutase (MnSOD) activity has been reported to
      be vital for protection against infarction. However, whether MnSOD is essential
      for exercise-induced protection against ventricular arrhythmias is unknown. We
      determined the effects of preventing the exercise-induced increase in MnSOD
      activity on arrhythmias during I-R resulting in myocardial stunning. Male rats
      remained sedentary or were subjected to successive bouts of endurance exercise.
      During in vivo myocardial I-R, the incidence of arrhythmias was significantly
      lower in the exercise-trained rats than in the sedentary rats as evidenced by the
      arrhythmia. When exercised rats were pretreated with antisense oligonucleotides
      directed against MnSOD, protection from arrhythmias was attenuated. Moreover, I-R
      resulted in significant increases in nitro-tyrosine (NT) in the sedentary group.
      Exercise abolished this I-R-induced NT formation but this protection was
      unchanged by antisense treatment. Protein carbonyls were increased by I-R, but
      neither exercise nor antisense treatment impacted carbonyl formation. These data
      demonstrate that an exercise-induced increase in MnSOD activity is important for
      protection against arrhythmias. The mechanism by which MnSOD provides protection
      does not appear to be linked to protein nitrosylation or oxidation.

PMID- 15454276
TI  - Protection against iron- and hydrogen peroxide-dependent cell injuries by a novel
      synthetic iron catalase mimic and its precursor, the iron-free ligand.
AB  - Hydrogen peroxide is involved in many types of cell injury and exerts most of its
      injurious effects in conjunction with chelatable iron. We previously described a
      synthetic nonporphyrin iron-containing catalase mimic, TAA-1/Fe. Its ligand TAA-1
      was designed for application in biological systems in which it is supposed to
      fulfill a dual task: it should chelate cellular labile iron and thus form the
      active catalase mimic, thereby decreasing levels of redox-active iron and
      enhancing the degradation of hydrogen peroxide. Here, we tested these novel
      compounds in cellular systems, i.e., in cultured hepatocytes and liver
      endothelial cells. Both the iron complex, i.e., the complete mimic, and the
      ligand, i.e., the putative precursor of this mimic, provided protection against
      endothelial cell injury induced by exogenous hydrogen peroxide. Furthermore, the
      ligand--but not (or less so) the complex--strongly protected both cell types
      against iron-dependent hypothermic injury and hepatocytes against iron-induced
      cell injury and against iron-dependent, histidine-induced injury. Together, these
      results demonstrate that the putative catalase mimic precursor TAA-1 is able to
      protect cells against iron- and/or hydrogen peroxide-dependent cell injuries and
      that--in line with our initial concept--it is likely to exert its protection by
      both iron chelation and hydrogen peroxide degradation.

PMID- 15454277
TI  - Peroxynitrite inhibits relaxation and induces pulmonary artery muscle contraction
      in the newborn rat.
AB  - Nitric oxide (NO) reacts with superoxide anion to form the peroxynitrite anion
      (ONOO-), a molecule with pulmonary vasodilator properties in the adult rat. The
      purpose of this study was to compare the effects of ONOO- on intrapulmonary
      arteries from the newborn (days 4-7), juvenile (day 14), and adult rat. Following
      thromboxane A2 (TXA2) analogue (U46619) prestimulation, newborn vessels were more
      sensitive to ONOO- -induced muscle contraction, compared to both the juvenile and
      the adult vessels. Peroxynitrite-induced contraction in newborn vessels was
      abrogated by ibuprofen, an endothelin B-receptor blocker (A-192621), or a rho
      kinase-specific inhibitor (Y27632) (all p < 0.01). Following KCl stimulation and
      TXA2 receptor blockade, ONOO- induced NO-dependent muscle relaxation in newborn
      vessels via stimulation of the endothelial and inducible nitric oxide synthases.
      However, in the presence of ONOO-, the pulmonary artery relaxation response to
      endothelium-dependent stimulation was significantly reduced (p < 0.01). Finally,
      newborn but not adult pulmonary arteries exposed to ONOO- showed a 10-fold
      increase in 8-isoprostane production, a possible mediator of ONOO- -induced
      contraction. We conclude that exposure to ONOO- results in a unique response in
      newborn intrapulmonary arteries characterized by increased 8-isoprostane
      generation, which we believe is responsible for its vasoconstrictor effect. This
      unique response potentially renders the newborn more susceptible to ONOO- 
      induced pulmonary hypertension than older animals.

PMID- 15454278
TI  - Ascorbic acid in nasal and tracheobronchial airway lining fluids.
AB  - Ascorbic acid (AA) is thought to be an important antioxidant in the respiratory
      tract, whose regulation is yet to be fully characterized. We investigated whether
      AA in respiratory tract lining fluids (RTLFs) can be augmented by oral
      supplementation with AA. Plasma, nasal lavage fluids (NLFs), induced sputum (IS),
      and saliva were analyzed for AA immediately before and 2 h after ingestion of 2 g
      of AA in 13 healthy subjects. Concentrations of AA (median and range) were 52.5
      (16.0-88.5), 2.4 (0.18-4.66), 2.4 (0.18-6.00), and 0.55 (0.18-18.90) micromol/l,
      respectively. Two hours after ingestion of AA, plasma AA increased 2-fold (p =
      .004), NLF AA increased 3-fold (p = .039), but IS and saliva AA did not increase.
      As AA concentrations in saliva and tracheobronchial secretions were low compared
      with other common extracellular components (such as urate), we evaluated the fate
      of AA in these fluids. Addition of AA to freshly obtained saliva or IS resulted
      in rapid depletion, which could be largely prevented or reversed by sodium azide
      or dithiothreitol. These findings suggest that oxidant-producing systems in
      saliva and airway secretions, such as heme peroxidases and other oxidizing
      substances, rapidly consume AA. Whereas oral supplementation resulted in
      detectable increases of AA in NLFs, its levels in tracheobronchial lining fluid,
      as measured by IS, were unaffected and remained relatively low, suggesting that
      AA may play a less significant antioxidant role in this compartment as compared
      with most other extracellular compartments.

PMID- 15454279
TI  - Contribution of reactive oxygen species to the regulation of Glut1 in two
      hemopoietic cell lines differing in cytokine sensitivity.
AB  - Glucose transport activity and its possible regulation by reactive oxygen species
      in two Glut1-expressing megakaryocytic cell lines, MO7e and B1647, differing in
      cytokine sensitivity were compared. Results show that: (1) In MO7e cells, glucose
      transport rate increased in response to thrombopoietin, granulocyte-macrophage
      colony-stimulating factor, or stem cell factor, due to a decreased Km. (2) A
      higher Vmax value was determined in B1647 cells, owing to the relative higher
      abundance of Glut1 on the plasmalemma; in these cells no change in glucose
      transport rate was observed on cytokine treatment. (3) The basal level of
      intracellular ROS was higher in B1647 than in M07e cells, where ROS production
      was enhanced upon cytokine exposure. (4) Basal or stimulated ROS production and
      Glut1 activity were significantly reduced by pretreating both cell lines with EUK
      134, a superoxide dismutase and catalase mimetic. (5) In MO7e cells, EUK-134
      brought back to control levels the Km values obtained on cytokine treatment,
      whereas in B1647 cells the antioxidant drastically reduced Vmax by decreasing the
      Glut1 content of the plasma membrane. Our data suggest that differences in acute
      regulation of glucose transport activity in the two cell lines may be related to
      differences in amplitude and spatial organization of ROS production.

PMID- 15454280
TI  - Effect of endocrine disruptor para-nonylphenol on the cell growth and oxygen
      radical generation in Escherichia coli mutant cells deficient in catalase and
      superoxide dismutase.
AB  - para-Nonylphenol (NP) had previously been found to have strong suppressive
      effects of growth of bacterial and yeast cells, and these effects were associated
      with NP-induced generation of radical oxygen species (ROS). In the present study,
      we determined that wild-type strains of Escherichia coli (CSH 7, SY-11, and IFO
      3545) were resistant to NP compared with other sensitive microorganisms reported
      previously. To elucidate the relationship between NP-induced ROS generation and
      cell growth inhibition in more detail, we analyzed the effect of NP on cell
      growth and survival of wild-type and mutant E. coli strains deficient in ROS
      scavenging enzymes such as catalase and superoxide dismutase (SOD). The SOD
      deficient strain QC 774 (sod A- and sod B-) was much more sensitive to NP than
      wild-type (CSH 7) and catalase-deficient (UM 1 kat E- and kat G-) strains. As a
      comparative experiment, when hydrogen peroxide was applied to the same growth and
      survival assays, UM 1 cells were more sensitive to hydrogen peroxide than QC 774
      and CSH 7. A chemiluminescence (CHL) experiment using MCLA (2-methyl-6-Lf
      methylphenyl]-3,7-dihydroimidazc [1,2-alpha] pyrazin-3-one) reflecting
      predominantly superoxide generation showed that NP caused marked CHL generation
      in QC 774 cells, but not in CSH 7 and UM 1 cells. However, the CHL experiment
      using L-012 reflecting predominantly hydroxyl radical and hypochlorite did not
      exhibit significant CHL generation in QC 774 cells at the same concentrations of
      NP. Furthermore, supplementation with SOD prevented NP-induced ROS generation and
      cell survival inhibition of QC 774 cells, but the catalase and metal-chelating
      agent deferoxamine did not have significant effects. These results suggest that
      one of the primary actions of NP in cells is the generation of superoxide which
      may be responsible for NP-induced cell growth inhibition.

PMID- 15454281
TI  - Vitamin C inhibits hypoxia-induced damage and apoptotic signaling pathways in
      cardiomyocytes and ischemic hearts.
AB  - Reactive oxygen species play a central role in myocardial ischemic injury and are
      a target for therapeutic intervention. Vitamin C is an essential antioxidant yet
      difficult to deliver in pharmacologic concentration to the myocardium. We found
      that adult rat cardiomyocytes accumulate vitamin C by transporting
      dehydroascorbic acid (DHA), the oxidized form of vitamin C, but do not transport
      ascorbic acid. Loading cells with vitamin C by DHA treatment resulted in
      resistance to hypoxia- and hypoxia/reoxygenation-induced cell death associated
      with the quenching of reactive oxygen species. When rats were injected with DHA
      before coronary occlusion, the ascorbic acid content in the heart was six to
      eight times higher than in untreated controls and myocardial infarction was
      reduced by 62%. DHA also provided significant protection when administered
      intravenously 2 h after coronary occlusion. In cardiomyocytes subjected to
      hypoxia/reoxygenation, DHA treatment resulted in decreased apoptosis associated
      with inhibition of Bax expression, caspase-3 activation, and cytochrome c
      translocation into the cytoplasm. DHA treatment also inhibited Jak2, STAT1, and
      STAT5 phosphorylation, and increased STAT3 phosphorylation, in hypoxic
      cardiomyocytes and ischemic myocardial tissue. Our findings suggest that DHA may
      be useful as a cardioprotectant in ischemic heart disease.

PMID- 15454282
TI  - 4-Hydroxynonenal regulates 26S proteasomal degradation of alcohol dehydrogenase.
AB  - The lipid peroxidation product 4-hydroxynonenal (4-HNE) has been shown to
      interfere with protein function. The goal of this study was to determine the
      effects of substrate modification by 4-HNE on protein degradation. Equine liver
      alcohol dehydrogenase (ADH, EC 1.1.1.1) treated with 2-fold molar excess 4-HNE
      was degraded by a rabbit reticulocyte lysate (RRL) system approximately 1.5-fold
      faster than control, while treatment with concentrations up to 100-fold molar
      excess aldehyde were inhibitory to degradation. Involvement of the 26S proteasome
      (EC 3.4.99.46) was demonstrated through the use of specific proteasome and ATPase
      inhibitors, and confirmed by measuring the extent of ADH polyubiquitination.
      Tryptic digestion and LC/MS analysis of 4-HNE-treated ADH identified modification
      of two zinc chelating Cys residues. Through molecular modeling experiments a
      conformational shift in both zinc-containing regions was predicted, with an
      approximate doubling of the distance between the structural zinc and its
      respective chelating residues. Modification of residues in the active site zinc
      binding motif resulted in less pronounced alteration in protein structure. The
      data presented here demonstrate accelerated ubiquitination and proteasomal
      degradation of ADH modified with 4-HNE, and suggest a conformational change after
      4-HNE docking as a mechanism behind these observations.

PMID- 15454283
TI  - Antioxidant effect of simvastatin is not enhanced by its association with alpha
      tocopherol in hypercholesterolemic patients.
AB  - Among the pleiotropic effects of statins, their antioxidant action may be
      involved in their protective effects. Thus, we investigated the antioxidant
      effect of simvastatin, associated or not with alpha-tocopherol, on levels of
      electronegative low-density lipoprotein (LDL-), nitrotyrosine, thiols
      (homocysteine, glutathione, cysteine, methionine), and lipid-soluble antioxidants
      in blood plasma of hypercholesterolemic subjects. In this study, 25
      hypercholesterolemic subjects were treated for 2 months with simvastatin (20
      mg/day) and with simvastatin (20 mg/day) + alpha-tocopherol (400 IU/day).
      Concentrations of thiols were determined by high-performance capillary
      electrophoresis-laser-induced fluorescene. Lipid-soluble antioxidants were
      determined by HPLC, and LDL-, and nitrotyrosine by ELISA. Simvastatin,
      independent of its association with alpha-tocopherol, reduced plasma
      concentrations of LDL-, nitrotyrosine, total cholesterol, and LDL cholesterol and
      the LDL cholesterol/HDL cholesterol ratio. Neither simvastatin nor simvastatin
      plus alpha-tocopherol altered plasma levels of the thiols analyzed. alpha
      Tocopherol did not change the antioxidant effect of simvastatin on the levels of
      LDL- and nitrotyrosine in hypercholesterolemic subjects. The reduction of LDL-
      and nitrotyrosine by simvastatin seems to be related to the pleiotropic effects
      of this statin, and it may have an important protective effect against
      endothelial dysfunction and atherosclerosis.

PMID- 15454284
TI  - Urinary excretion of DNA repair products correlates with metabolic rates as well
      as with maximum life spans of different mammalian species.
AB  - Using recently developed methodology, which includes HPLC prepurification
      followed by GC/MS with isotope dilution, we analyzed urinary excretion of
      possible repair products of oxidative DNA damage-8-oxo-7,8-dihydroguanine (8
      oxoGua), 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), and 5
      (hydroxymethyl)uracil (5-HMUra)-in mammalian species that substantially differ in
      metabolic rate and longevity, namely, mice, rats, rabbits, dogs, pigs, and
      humans. We found highly significant, positive correlations between specific
      metabolic rates of the animals studied and their excretion rates for all the
      modifications analyzed with respective r values for the lesions of (8-oxoGua) r =
      .891, p < .01; (8-oxodG) r = .998, p < .001; and (5-HMUra) r = .949, p < .005.
      However, only 8-oxoGua significantly correlates negatively with maximum life span
      (MLSP) (r = -.928, p < .01). Despite substantial differences in MLSP between
      humans and pigs (120 and 27 years, respectively), the rates of excretion of all
      measured modifications were very similar. The urinary levels of all measured
      modifications found in our study for mouse and humans account respectively for
      about 34,000 and 2800 repaired events per average cell, per 24 h. It is therefore
      possible that the high metabolic rate in mice (or other short-lived animals) may
      be responsible for severe everyday oxidative DNA insults that may be accumulated
      faster than in long-lived species.

PMID- 15454285
TI  - HSP25 protects skeletal muscle cells against oxidative stress.
AB  - Reactive oxygen species (ROS) may cause skeletal muscle degeneration in a number
      of pathological conditions. Small heat shock proteins (HSPs) have been found to
      confer resistance against ROS in different cell types; however, the importance of
      their antioxidant function in skeletal muscle cells remains to be determined. In
      the present study, differentiation of skeletal myoblasts resulted in protection
      against hydrogen peroxide-induced cell death and protein oxidation. This
      differentiation-induced resistance to oxidative stress was associated with
      increased protein expression of HSP25, increased glutathione levels, and
      glutathione peroxidase activity, but little change in catalase activity.
      Overexpression of HSP25 in stably transfected myoblasts produced dose-dependent
      protection against hydrogen peroxide-induced damage that was associated with
      increased glutathione levels and glutathione peroxidase activity. Inhibition of
      glutathione synthesis with buthionine sulfoximine abrogated the protection
      induced by HSP25 overexpression. These findings indicate that HSP25 may play a
      key role in regulating the glutathione system and resistance to ROS in skeletal
      muscle cells.

PMID- 15454286
TI  - Nitric oxide protects anterior pituitary cells from cadmium-induced apoptosis.
AB  - Cadmium (Cd2+) is a potent toxic metal for both plants and animals. Chronic
      exposure to low doses of Cd2+ results in damage to several organs. We have
      previously reported that Cd2+ induces apoptosis in anterior pituitary cells by a
      caspase- and oxidative stress-dependent mechanism. Nitric oxide (NO) synthesis is
      affected by Cd2+ in several systems. NO has been shown to be either
      cytoprotective or cytotoxic in many systems. The aim of this study was to
      evaluate the possible participation of NO in the cytotoxic effect of Cd2+ on rat
      anterior pituitary cells. Cell viability was evaluated by mitochondrial
      dehydrogenase activity assay and confirmed by microscopy, studying nuclear
      morphology. Here we show that DETA NONOate ((Z)-1-[2 (2-aminoethyl)-N-(2
      ammonioethyl)amino]diazen-1-ium-1,2-diolate), a long-term NO donor, at
      concentrations below 0.5 mM, reduces nuclear condensation and fragmentation and
      reverses the decrease in cellular activity induced by Cd2+. Cd2+, by itself,
      induced NO synthesis, and inhibition of this synthesis enhanced Cd2+
      cytotoxicity. NO also prevented caspase-3 activation and lipidic peroxidation
      induced by Cd2+. The NO/cGMP pathway does not seem to be involved in the
      cytoprotective effect of NO. These results indicate that NO has a cytoprotective
      role in Cd2+ -induced apoptosis, suggesting that endogenous NO could have a
      physiological role in protecting anterior pituitary cells.

PMID- 15454287
TI  - Mitochondrial nitric oxide metabolism in rat muscle during endotoxemia.
AB  - In this study, heart and diaphragm mitochondria produced 0.69 and 0.77 nmol
      nitric oxide (NO)/min mg protein, rates that account for 67 and 24% of maximal
      cellular NO production, respectively. Endotoxemia and septic shock occur with an
      exacerbated inflammatory response that damages tissue mitochondria. Skeletal
      muscle seems to be one of the main target organs in septic shock, showing an
      increased NO production and early oxidative stress. The kinetic properties of
      mitochondrial nitric oxide synthase (mtNOS) of heart and diaphragm were
      determined. For diaphragm, the KM values for O2 and L-Arg were 4.6 and 37 microM
      and for heart were 3.3 and 36 microM. The optimal pH for mtNOS activity was 6.5
      for diaphragm and 7.0 for heart. A marked increase in mtNOS activity was observed
      in endotoxemic rats, 90% in diaphragm and 30% in heart. Diaphragm and heart
      mitochondrial O2*- and H2O2 production were 2- to 3-fold increased during
      endotoxemia and Mn-SOD activity showed a 2-fold increase in treated animals,
      whereas catalase activity was unchanged. One of the current hypotheses for the
      molecular mechanisms underlying the complex condition of septic shock is that the
      enhanced NO production by mtNOS leads to excessive peroxynitrite production and
      protein nitration in the mitochondrial matrix, causing mitochondrial dysfunction
      and contractile failure.

PMID- 15454288
TI  - Protein-bound kynurenine is a photosensitizer of oxidative damage.
AB  - Human lens proteins become progressively modified by tryptophan-derived UV filter
      compounds in an age-dependent manner. One of these compounds, kynurenine,
      undergoes deamination at physiological pH, and the product binds covalently to
      nucleophilic residues in proteins via a Michael addition. Here we demonstrate
      that after covalent attachment of kynurenine, lens proteins become susceptible to
      photo-oxidation by wavelengths of light that penetrate the cornea. H2O2 and
      protein-bound peroxides were found to accumulate in a time-dependent manner after
      exposure to UV light (lambda > 305-385 nm), with shorter-wavelength light giving
      more peroxides. Peroxide formation was accompanied by increases in the levels of
      the protein-bound tyrosine oxidation products dityrosine and 3,4
      dihydroxyphenylalanine, species known to be elevated in human cataract lens
      proteins. Experiments using D2O, which enhances the lifetime of singlet oxygen,
      and azide, a potent scavenger of this species, are consistent with oxidation
      being mediated by singlet oxygen. These findings provide a mechanistic
      explanation for UV light-mediated protein oxidation in cataract lenses, and also
      rationalize the occurrence of age-related cataract in the nuclear region of the
      lens, as modification of lens proteins by UV filters occurs primarily in this
      region.

PMID- 15454289
TI  - Kinetic analysis of thapsigargin-induced thymocyte apoptosis.
AB  - Thapsigargin addition to thymocytes increased cytosolic Ca2+ by a factor of 8.5
      with a time for half maximal effect (t1/2) of 2.5 min. Calcium signaling
      increased mitocondrial and endoplasmic reticulum nitric oxide synthase (NOS)
      activities by five and six times, with t1/2 of 16 and 48 min, respectively,
      followed by increases of 140% in intracellular [H2O2], 73% in hydroperoxide
      content, and 250% in thiobarbituric reactive substance content, with t1/2 of 13,
      27, and 30 min, respectively. Mitochondrial dysfunction followed, and was
      characterized by decreased respiratory control, membrane depolarization, and
      decrease cytochrome c content release, processes with t1/2 of 101, 129, and 133
      min, respectively. Increased UDP-GT gene expression, observed by mRNA synthesis,
      and the enzymatic activity of this protein had t1/2 of 52 and 187 min,
      respectively. These events were followed by caspase-3 activation (t1/2 = 210 min)
      and DNA laddering (t1/2 = 260 min) at the completion of the cell death program.
      Preincubation of thymocytes with NOS inhibitors (NG-methyl-L-arginine and L
      Nomega-nitro-L-arginine methylester) halted the whole process through inhibition
      of mitochondrial and endoplasmic reticulum NOS activities and of DNA laddering.

PMID- 15454290
TI  - Oxidative stress and depletion of hepatic long-chain polyunsaturated fatty acids
      may contribute to nonalcoholic fatty liver disease.
AB  - Human nonalcoholic fatty liver disease (NAFLD) associated with obesity is
      characterized by depletion of hepatic n-3 long-chain polyunsaturated fatty acids
      (LCPUFA), with lower LCPUFA product/precursor ratios and higher 18:1n-9 trans
      levels in adipose tissue, both in patients with steatosis and in those with
      steatohepatitis. These changes point to modification of gene expression, with
      decreased fatty acid oxidation and triacylglycerol export and enhanced lipid
      synthesis, thereby leading to fat accumulation in the liver. Changes in oxidative
      stress-related parameters indicate a moderate enhancement in the pro-oxidant
      status of the liver in steatosis, which is further exacerbated in
      steatohepatitis. It is proposed that oxidative stress plays a dual role in NAFLD
      by contributing to steatosis due to higher peroxidation of LCPUFA, in addition to
      defective fatty acid desaturation and diet imbalance, and by promoting
      progression of steatosis to steatohepatitis, features that might involve changes
      in the activity of transcriptional mediators.

PMID- 15454291
TI  - In vitro inhibition of human neutrophil elastase by oleic acid albumin
      formulations from derivatized cotton wound dressings.
AB  - Human neutrophil elastase (HNE) is elevated in chronic wounds. Oleic acid albumin
      formulations that inhibit HNE may be applicable to treatment modalities for
      chronic wounds. Oleic acid/albumin formulations with mole ratios of 100:1, 50:1,
      and 25:1 (oleic acid to albumin) were prepared and found to have dose response
      inhibition properties against HNE. The IC50 values for inhibition of HNE with
      oleic acid/albumin formulations were 0.029-0.049 microM. Oleic acid/albumin (BSA)
      formulations were bound to positively and negatively charged cotton wound
      dressings and assessed for elastase inhibition using a fiber bound formulation in
      an assay designed to mimic HNE inhibition in the wound. Cotton derivatized with
      both carboxylate and amine functional groups were combined with oleic
      acid/albumin formulations at a maximum loading of 0.030 mg oleic acid + 0.14 mg
      BSA/mg fiber. The IC50 values for inhibition of HNE with oleic acid/albumin
      formulations bound to derivatized cotton were 0.26-0.42 microM. Release of the
      oleic acid/albumin formulation from the fiber was measured by measuring oleic
      acid levels with quantitative GC analysis. Approximately, 35-50% of the fiber
      bound formulation was released into solution within the first 15 min of
      incubation. Albumin was found to enhance the rate of elastase hydrolysis of the
      substrate within a concentration range of 0.3-50 g/L. The acceleration of HNE
      substrate hydrolysis by albumin required increased concentration of inhibitor in
      the formulation to obtain complete inhibition of HNE. Oleic acid formulations
      prepared with albumin enable transport, solubility and promote dose response
      inhibition of HNE from derivatized cotton fibers under aqueous conditions
      mimicking the chronic wound.

PMID- 15454292
TI  - Influence of the solvent composition on the aerosol synthesis of pharmaceutical
      polymer nanoparticles.
AB  - Spherical, Eudragit L100 polymer nanoparticles with and without a ketoprofen drug
      were prepared by a novel aerosol flow reactor method. In this method, the polymer
      solution is sprayed to form nanosized droplets followed by the evaporation of a
      solvent. A purpose of the work was to explore the effect of solvent, solvent
      mixture, and co-solute (ketoprofen) on the formation of polymer particle, and
      particularly on particle morphology. The solvents used, i.e. ethanol, THF,
      toluene, and water, were selected according to their vapor pressure and
      dissolution capability for the polymer. At the polymer concentration range from
      0.2 to 1.5 g/l of the starting solution, the geometric number mean diameters
      (GMD) of the particles increased from 75 to 130 nm and from 65 to 100 nm from the
      solutions of ethanol and THF, respectively. Particle morphology was observed by a
      scanning electron microscope (SEM). Particles changed from collapsed to irregular
      via spherical shape in the course of the decreasing solubility of the polymer in
      the medium. This is critically dependent on the solvent evaporation rate as well
      as the solute solubility, i.e. fast evaporative removal of solvent results in
      collapsed particles whereas low solubility results in irregular particles.
      Interplay between the vapor pressure of the solvents and the polymer solubility
      in the medium made possible to prepare particles with more complicated structures
      such as shriveled and blistery structures. The particle morphology as detected by
      SEM did not change when 10 wt.% of ketoprofen was added to the precursor
      solution.

PMID- 15454293
TI  - Bioequivalence determination of topical ketoprofen using a dermatopharmacokinetic
      approach and excised skin penetration.
AB  - Ketoprofen is a photolabile drug. The aim of the present study was to compare the
      bioavailability of ketoprofen in a photo-stabilised formulation with a gel
      without photoprotection using a new dermatopharmacokinetic tape-stripping model
      and an established ex vivo penetration method using human skin. Analyses of the
      stratum corneum showed that during the first 45 min about 12 microg/cm2
      ketoprofen was absorbed into the skin from the formulations. The area under the
      ketoprofen content-time curve (AUC0-6 h) for the ratio photo-stabilised
      gel/transparent gel was 73% with a 90% confidence interval (CI) 65-83. The rate
      of penetration of ketoprofen through isolated skin was approximately 0.2
      microg/cm2 h for both formulations. AUC0-36 h for the ratio was 84% with 90% CI
      64-105. Thus, the two methods did not disagree in terms of relative efficacy of
      the two gels. However, the difference obtained in vivo was statistically
      significant, whereas no significant data arise from the ex vivo study. Comparing
      the amount of ketoprofen in the skin after 45 min with the amount penetrated
      through the excised skin during 36 h, suggests a change in the thermodynamic
      activity of ketoprofen during the exposure. A supersaturated formulation may well
      have been formed initially due to evaporation of ethanol.

PMID- 15454294
TI  - Surfactant vesicle-mediated delivery of DNA vaccines via the subcutaneous route.
AB  - Compared to naked DNA immunisation, entrapment of plasmid-based DNA vaccines into
      liposomes by the dehydration-rehydration method has shown to enhance both
      humoural and cell-mediated immune responses to encoded antigens administered by a
      variety of routes. In this paper we have compared the potency of lipid-based and
      non-ionic surfactant based vesicle carrier systems for DNA vaccines after
      subcutaneous immunisation. Plasmid pI.18Sfi/NP containing the nucleoprotein (NP)
      gene of A/Sichuan/2/87 (H3N2) influenza virus in the pI.18 expression vector was
      incorporated by the dehydration-rehydration method into various vesicle
      formulations. The DRV method, entailing mixing of small unilamellar vesicles
      (SUV) with DNA, followed by dehydration and rehydration, yielded high DNA vaccine
      incorporation values (85-97% of the DNA used) in all formulations. Studies on
      vesicle size revealed lipid-based systems formed cationic submicron size vesicles
      whilst constructs containing a non-ionic surfactant had significantly large z
      average diameters (>1500 nm). Subcutaneous vesicle-mediated DNA immunisation
      employing two DRV(DNA) formulations as well as naked DNA revealed that humoural
      responses (immunoglobulin total IgG, and subclasses IgG1 and 1gG2a) engendered by
      the plasmid encoded nucleoprotein were substantially higher after dosing twice,
      28 days apart with 10 microg DRV-entrapped DNA compared to naked DNA. Comparison
      between the lipid and non-ionic based vesicle formulations revealed no
      significant difference in stimulated antibody production. These results suggest
      that, not only can DNA be effectively entrapped within a range of lipid and non
      ionic based vesicle formulations using the DRV method but that such DRV vesicles
      containing DNA may be a useful system for subcutaneous delivery of DNA vaccines.

PMID- 15454295
TI  - Effect of cell-surface glycosaminoglycans on cationic carrier combined with low
      MW PEI-mediated gene transfection.
AB  - Glycosaminoglycans (GAGs) are negatively charged polysaccharides that are found,
      e.g. on cell surface. GAGs have been reported to influence gene transfection. We
      have previously reported that cationic lipid-mediated gene transfection can be
      improved by combining a small polyethylenimine (PEI) with cationic lipids. In the
      present study, we examined if GAGs have any effect on the synergism of small PEIs
      and other cationic carriers. We used wild-type CHO (GAG+) and pgsB-618 cells (GAG
      ). Transfection efficiency was studied using lacZ and GFP reporter genes. We
      found that GAGs decreased the overall level of transgene expression in a reagent
      dependent manner, but the synergism caused by low-MW PEIs was less affected.
      There were no major differences between cell lines in cellular uptake or
      intracellular localization of plasmids when measured with flow cytometry and
      confocal microscopy, respectively. In conclusion, cell-surface GAGs interfere
      with transfection efficiency of different cationic reagents, but that is not
      necessarily related to the synergy of small PEIs and cationic lipids.

PMID- 15454296
TI  - The crystallisation of a model hydrophobic drug (terfenadine) following exposure
      to humidity and organic vapours.
AB  - Terfenadine was selected as a model drug as it readily converts to the amorphous
      form, is chemically stable and is hydrophobic. Amorphous terfenadine beads were
      exposed to water vapour (different RH values) and the change in crystallinity was
      monitored using isothermal microcalorimetry. It was found that a small amount of
      the surface crystallised and then the process stopped (after about 9 weeks even
      though storage continued for ca. 2 years). The self-limiting crystallisation was
      due to water having limited access to the surface, believed to be at certain
      cracks and pores. Water sorption data were modelled such that it was possible to
      compare rates of sorption at different RH values and on fresh and aged material.
      It was shown that sorption was slower with reducing RH and also much slower on
      aged samples that had relaxed and reduced the size of surface defects. Mixtures
      of ethanol and water yielded a vapour that produced increasing rates of
      crystallisation as the ethanol content increased, but which only crystallised the
      outer surface of the beads and not the core. A mixture of ethanol and n-propanol
      caused complete crystallisation, because the propanol was sufficiently
      hydrophobic to absorb throughout the bead and lower Tg. An isothermal
      microcalorimetry method was described that allowed quantification of the
      amorphous content. The work has demonstrated the complexity of the
      crystallisation of hydrophobic amorphous materials when exposed to various
      vapours.

PMID- 15454297
TI  - Effect of hydroxypropyl-beta-cyclodextrin-complexation and pH on solubility of
      camptothecin.
AB  - The influence of both pH and complexation by hydroxypropyl-beta-cyclodextrin (HP
      beta-CD) on the overall solubility of camptothecin (CPT) was studied, with
      particular focus on the equilibrium between its lactone- and carboxylate-form.
      Phase solubility studies at therapeutically relevant pH values (pH 5.5-7.0) and
      physiologically acceptable HP-beta-CD-concentrations (0-25% (w/v)) were
      performed, and amounts of solubilized CPT quantified by HPLC. The solubility of
      CPT increased with both increasing pH and HP-beta-CD-concentration. The apparent
      complexation constant (KC) decreased with increasing pH (245 M(-1) at pH 5.5; 184
      M(-1) at pH 7.0). The lactone-carboxylate equivalence point shifted from a pH
      value of 6.8-7.0 and 7.1 with 0, 10 and 25% HP-beta-CD, respectively. The lactone
      carboxylate-ratios from the equilibrium study were applied to the phase
      solubility data, and the lactone- and carboxylate concentrations at 0, 10 and 25%
      HP-beta-CD calculated. Separate complexation constants (KC) for the carboxylate
      CPT and lactone-CPT could thus be derived, and found to be 113 +/- 7 and 260 +/-
      18 M(-1), respectively. This allows the prediction of amounts of both lactone-
      and carboxylate-CPT solubilized at any HP-beta-CD concentration and pH
      combination.

PMID- 15454298
TI  - Anomalous effect of compression pressure on the brittle fracture tendency of
      alpha-cellulose tablets.
AB  - The effect of varying the compression pressure on the brittle fracture tendency
      of alpha-cellulose and lactose tablets has been investigated. Tablet tensile
      strength, (T), packing fraction, (Pf), and brittle fracture index (BFI) were
      determined at different compression pressures (0.82, 1.22 and 1.63 MPa). In
      another aspect of the study, alpha-cellulose and tapioca powders were mixed in
      various proportions to obtain powders of varying plastoelasticity. Their
      tableting characteristics T, Pf and BFI were also determined at the different
      compression pressures. The polymer, alpha-cellulose displayed the characteristics
      of plastic compression--a low BFI but high T and Pf values while lactose
      displayed the characteristics of elastic compression--a high BFI but low T and Pf
      values. The degree of plastic compression decreased as the proportion of tapioca
      in the powder mixture increased from 0 to 50% w/w. Higher concentrations of
      tapioca >50% produced crumbly tablets at all compression pressures, thus
      indicating that tapioca is highly elastic. Increase in the compression pressure
      caused an increase in the BFI values of lactose tablets, 0.39-0.76 but a decrease
      in the BFI values of alpha-cellulose tablets, 0.38-0.09. This decrease became
      less pronounced as the plasticity of the powder mixtures decreased. The
      difference in the response of the tablets to the change in compression pressure
      relates to the difference in the plastoelasticity of the materials tested.

PMID- 15454299
TI  - A novel formulation technique for metered dose inhaler (MDI) suspensions.
AB  - Metered dose inhalers (MDIs) are a widely used dosage form for pulmonary delivery
      of anti-asthmatic drugs. However, with the phase-out of chlorofluorocarbon (CFC)
      propellants and need to switch to the alternative pharmaceutically approved
      hydrofluoroalkane (HFA) propellants, the MDI formulator was faced with several
      technical challenges. Product components such as valves and elastomers needed to
      re-designed, and, due to the limited solubility of the commonly used surfactants
      in the HFA propellants, novel surfactants were developed or co-solvents were used
      to bring the conventional surfactants into solution. This paper describes a novel
      formulation approach for HFA based metered-dose inhalers. A physically stable
      micro-suspension of the model drug, budesonide, was formulated by an in situ
      precipitation process using a hydrophilic stabilizer in the propellant system. A
      network-like structure of the precipitated drug and excipient was formed and
      resulted in physically stable suspensions in which the solid phase remained
      suspended in the propellant system for several weeks. Through life dose
      uniformity testing of MDI units containing formulations of budesonide produced by
      the novel process, was consistent and within the limits specified by the FDA
      draft guidance on metered dose inhalers. The fine particle fraction of the
      budesonide formulations showed a dependence on formulation composition and
      aerosol hardware (canister and actuator) illustrating flexibility in optimizing
      the product using this novel in situ formulation technique.

PMID- 15454300
TI  - Approaches to determine the enthalpy of crystallisation, and amorphous content,
      of lactose from isothermal calorimetric data.
AB  - Amorphous lactose will crystallise rapidly if its glass transition temperature is
      reduced below its storage temperature. This is readily achieved by storing
      samples at ambient temperature and a relative humidity (RH) of greater than 50%.
      If the sample is monitored in an isothermal microcalorimeter as it crystallises,
      the heat changes associated with the event can be measured; indeed this is one of
      the methods used to quantify the amorphous content of powders and formulations.
      However, variations in the calculation methods used to determine these heat
      changes have led to discrepancies in the values reported in the literature and
      frequently make comparison of data from different sources difficult. Data
      analysis and peak integration software allow the selection and integration of
      specific areas of complex traces with great reproducibility; this has led to the
      observation that previously ignored artefacts are in fact of sufficient magnitude
      to affect calculated enthalpies. In this work a number of integration
      methodologies have been applied to the analysis of amorphous spray-dried lactose,
      crystallised under 53 or 75% RH at 25 degrees C. The data allowed the selection
      of a standard methodology from which reproducible heat changes could be
      determined. The method was subsequently applied to the analysis of partially
      amorphous lactose samples (containing 1-100% (w/w) amorphous content) allowing
      the quantification limit of the technique to be established. It was found that
      the best approach for obtaining reproducible results was (i) to crystallise under
      an RH of 53%, because this slowed the crystallisation response allowing better
      experimental measurement and (ii) to integrate all the events occurring in the
      ampoule, rather than trying to select only that region corresponding to
      crystallisation, since it became clear that the processes occurring in the cell
      overlapped and could not be deconvoluted. The technique was able to detect
      amorphous contents as low as 1% (w/w), using this integration strategy, although
      it was observed that the calibration plot constructed showed a negative deviation
      from linearity. It is suggested that such non-ideal behaviour results from the
      formation of varying ratios of alpha-lactose monohydrate, anhydrous alpha-lactose
      and anhydrous beta-lactose.

PMID- 15454301
TI  - Modified push-pull osmotic system for simultaneous delivery of theophylline and
      salbutamol: development and in vitro characterization.
AB  - An oral osmotic system which can deliver theophylline and salbutamol sulphate
      simultaneously for extended period of time was developed and characterized in a
      view to reduce the problems associated with the multidrug therapy of asthma.
      Simple controlled porosity osmotic pump contained both drugs (in freely soluble
      form) did not provide satisfactory extended release of theophylline. A modified
      two-layered, push-pull osmotic system was developed by using the basic designs of
      various oral osmotic pumps, such as controlled porosity osmotic pump (CPOP),
      elementary osmotic pump (EOP) and push-pull osmotic pump (PPOP). Scanning
      electron microscopy of cellulose acetate coating membrane after dissolution
      revealed that 25% (w/w) of sorbitol can be used as an optimized concentration of
      pore forming agent with 25% (w/w) of plasticizer, which was kept constant.
      Formulations were initially developed for theophylline and the release was
      optimized by using two different soluble forms of theophylline with varying
      amount of hydrophilic polymer mixture in upper layer and polyethylene oxide
      (expandable hydrogel) in lower layer. Further, the release of salbutamol sulphate
      was optimized by keeping the drug in upper or lower layer or both layers. In
      vitro release studies showed satisfactory controlled release profiles of both
      drugs. The release profiles of both drug statistically compared with respective
      marketed controlled release formulations. An optimized system was selected to
      study the effect of concentration of pore forming agent and orifice diameter on
      the release of both drugs.

PMID- 15454302
TI  - The role of solid nanoparticle technology in the parenteral delivery of poorly
      water-soluble drugs.
AB  - Water insolubility has always been a key obstacle in pharmaceutical formulation,
      affecting formulation stability and drug bioavailability. Approaches for
      achieving complete dissolution often have disadvantages associated with the large
      quantities of required excipients. Small-particle suspensions (200 nm-2 microm),
      consisting essentially of pure drug, require only a minimum amount of surface
      active agent for stabilization. Such suspensions may be formulated for rapid
      dissolution, thus achieving pharmacokinetic properties similar to those of a
      solution, or drug insolubility may be leveraged to afford prolonged in vivo
      release. In both situations, higher dosing may be possible than with a drug
      solution. This may afford enhanced efficacy at reduced excipient concentrations
      with potentially less toxicity. We present a brief introduction to the
      pharmaceutical technology of pure submicron drug particles in relationship to
      other dosage forms, and study examples are presented to underscore the potential
      benefits of this approach in parenteral delivery.

PMID- 15454303
TI  - Investigation on the flow behavior of dispersions of solid triglyceride
      nanoparticles.
AB  - The flow behavior of low concentrated dispersions of solid lipid nanoparticles
      consisting of either trimyristin, tripalmitin or tristearin and different ionic
      and nonionic stabilizer blends were investigated using a rheometer with cone and
      plate apparatus and an Ubbelohde type capillary viscometer. The data demonstrate
      a remarkable influence of the matrix material, the stabilizer composition and the
      presence of small amounts of sodium chloride on the formulations' rheological
      properties. A significant increase in dispersion viscosity was found in the
      triglyceride sequence trimyristin < tripalmitin < tristearin. This effect can be
      clearly attributed to an increase in particle shape anisometry with increasing
      length of the lipid's fatty acid chains. Surfactants, which are present during
      the crystallization of the dispersed lipid seem to have an additional effect on
      the nanoparticle shape. Beyond this, ionic surfactants and other salts affect the
      dispersion viscosity by altering the dimension of the electrical double layer
      ("second electroviscous effect").

PMID- 15454304
TI  - The effect of PAMAM dendrimer generation size and surface functional group on the
      aqueous solubility of nifedipine.
AB  - The aim of this study was to investigate the effect of low generation (G0-G3)
      ethylenediamine (EDA) core poly(amidoamine) (PAMAM) dendrimers on the aqueous
      solubility of nifedipine. The aqueous solubility of nifedipine was measured in
      the presence of dendrimers at 30 degrees C in Tris buffers at pH 4, 7, and 10
      using the traditional rotary bottle method. Results showed that generation size,
      surface functional group and the pH of the aqueous media determined the aqueous
      solubility of nifedipine and that solubility profiles were of the Higuchi AL
      type. Both amine and ester terminated dendrimers caused the highest increase in
      nifedipine solubility at pH 7. The order in which the dendrimers increased the
      solubility at pH 7 was G2.5 > G3 > G1.5 > G2 > or = G0.5 > G1 > G0. In addition,
      at each pH, the solubility of nifedipine was greater in the presence of ester
      terminated dendrimers compared to the amine-terminated dendrimers possessing the
      same number of surface functional groups. The pH and surface functional group
      dependent increase in nifedipine solubility caused by the dendrimers was likely
      due to changes in the degree of protonation of the dendrimers. A decrease in the
      protonation of dendritric amines was expected to promote hydrogen bond formation
      between the tertiary amines within the dendrimer cavity and the nifedipine
      molecule.

PMID- 15454305
TI  - Modulatory effect of gentisic acid on the augmentation of biochemical events of
      tumor promotion stage by benzoyl peroxide and ultraviolet radiation in Swiss
      albino mice.
AB  - The present study was carried out to study the effect of gentisic acid (2,5
      dihydroxybenzoic acid (2,5-DHBA)) on the tumor promotion related events of
      carcinogenesis in murine skin. Benzoyl peroxide (BPO) (20 mg/0.2 ml/animal) and
      ultraviolet radiations (UVR) (0.420 J/m2/s) were used to induce tumor promotion
      response and oxidative stress and caused significant depletion in the
      detoxification and antioxidant enzyme armory with concomitant elevation in
      malondialdehyde (MDA) formation, hydrogen peroxide (H2O2) generation, ornithine
      decarboxylase (ODC) activity and unscheduled DNA synthesis. However, gentisic
      acid pretreatment at two different doses restored the levels of the above said
      parameters (P < 0.05) in a dose-dependent manner except in the case of ODC
      activity. Therefore, we propose that it might suppress the promotion stage via
      inhibition of oxidative stress but may not affect the polyamine biosynthetic
      pathway.

PMID- 15454306
TI  - Enhancement of genotoxic effects in the comet assay with human blood samples by
      aphidicolin.
AB  - The comet assay (single cell gel electrophoresis) has become increasingly used in
      human biomonitoring. In its standard version at pH > 13, DNA lesions such as DNA
      double-strand breaks (DSB), DNA single strand breaks (SSB) and alkali-labile
      sites (ALS) lead to increased DNA migration. Besides DNA damage, strand break
      formation during excision repair can also increase DNA migration. Inhibitors of
      DNA repair have been shown to enhance the DNA effects of mutagens and the use of
      repair inhibitors has been proposed for human biomonitoring studies to increase
      the sensitivity of the comet assay. To further evaluate the usefulness of such an
      approach we performed an experimental study with human blood and tested the
      enhancing effect of aphidicolin (APC) on DNA effects induced by different
      mutagens. Our results clearly show that APC enhances the genotoxic effects of
      benzo[a]pyrene diolepoxide (BPDE), bischloroethylnitrosurea (BCNU) and methyl
      methanesulfonate (MMS), but has no significant effect on gamma radiation-induced
      DNA effects. The enhancing effect is seen in unstimulated and PHA-stimulated
      blood, indicating repair activity under both conditions but the effect is
      stronger in stimulated blood. Our results indicate that APC can be used to
      increase the sensitivity of the comet assay towards a broad spectrum of induced
      primary DNA lesions and support the usefulness of this approach. However, for
      human biomonitoring, a sensitive protocol still has to be established.

PMID- 15454307
TI  - Polychlorinated biphenyl mixtures (Aroclors) induce apoptosis via Bcl-2, Bax and
      caspase-3 proteins in neuronal cell cultures.
AB  - Polychlorinated biphenyls (PCBs) are a group of persistent and widely dispersed
      environmental pollutants, some of which may be neurotoxic. In the present study,
      we have investigated the effect of PCB commercial mixtures (Aroclors) on neuronal
      cell cultures by assessing cell viability and apoptotic cell death. We have
      combined morphological and biochemical techniques to establish the relevance of
      apoptosis in neuronal cell death induced by Aroclors. Treatment with both Aroclor
      1248 and Aroclor 1260 caused the loss of cell viability and accelerated apoptosis
      both in a concentration- and time-dependent manner. However, the extent of
      apoptosis resulted greater for Aroclor 1248 than for Aroclor 1260. This is
      correlated with the loss of cell viability since Aroclor 1248 is more cytotoxic.
      The apoptosis induced by Aroclors involves the increase of caspase-3 activity. To
      correlate the caspase-3 activity with respect to changes in protein processing,
      caspase-3 precursor protein (procaspase-3) was evaluated by Western blot
      analysis. Also, Bcl-2 and Bax protein were assessed in order to elucidate the
      cell death machinery induced in cortical neuronal cell cultures by Aroclor 1248.
      The results indicate that the increase in Aroclor-induced apoptosis correlates
      with a reduction in the expression of antiapoptotic Bcl-2 and an increase in the
      expression of proapoptotic Bax. These results suggest that, with our experimental
      conditions, Aroclors induce apoptosis in primary cultures of cortical neurons via
      proteins of the Bcl-2 and caspase families.

PMID- 15454308
TI  - Reduction of chrysotile asbestos-induced genotoxicity in human peripheral blood
      lymphocytes by garlic extract.
AB  - Asbestos fibers are well known environmental carcinogen, however, the underlying
      mechanisms of their action have still not clearly been identified. Asbestos is
      capable of depleting glutathione and generating reactive oxygen species (ROS),
      which are important mediators of damage in biological system. Asbestos-induced
      mutagenecity, may be mediated by the generation. It is known that a number of
      scavengers and antioxidants attenuate asbestos-induced ROS release. Furthermore,
      it is known that garlic, contains numerous sulfur compounds and glutathione
      precursors which act as antioxidants and also demonstrate anticarcinogenic
      properties. The aim of this study was to investigate whether garlic extract has
      any influence on asbestos-mediated genotoxicity. As an assay system, we applied
      the micronucleus assay, sister chromatid exchanges, and chromosomal aberrations
      with human peripheral blood lymphocytes, which has already been used to analyze
      the genotoxicity of asbestos fibers. Our results indicate that garlic extract,
      when administered to the lymphocytes cell culture simultaneously with chrysotile
      reduced the rates of micronucleus formation, sister chromatid exchanges, and
      chromosomal aberrations significantly. We conclude that garlic extract may be an
      efficient, physiologically tolerable quencher of asbestos-mediated genotoxicity.

PMID- 15454309
TI  - High sucrose consumption potentiates the sub-acute cadmium effect on Na+/K+ 
      ATPase but not on delta-aminolevulinate dehydratase in mice.
AB  - High sucrose consumption and sub-acute cadmium effects on delta-ALA-D activity,
      Na+/K+ -ATPase activity, and lipid peroxidation were studied in different tissues
      of mice. Experimental groups were control, high sucrose (200 g/L), cadmium (5
      mg/kg/day, subcutaneously, two consecutive doses in different days in each week,
      during 4 weeks), and sucrose plus cadmium. There was a significant increase in
      TBARS levels for spleen and liver in cadmium and sucrose plus cadmium groups.
      Testicular delta-ALA-D activity of cadmium and sucrose plus cadmium-treated
      animals was significantly inhibited, whereas the enzyme activity increased in
      blood (cadmium and sucrose plus cadmium groups) and spleen (sucrose plus cadmium
      group). Na+/K+ -ATPase activity was significantly decreased in brain and kidney
      of sucrose plus cadmium-treated animals. Our data indicate that sub-acute cadmium
      treatment inhibits significantly testicular delta-ALA-D activity, demonstrating
      the prevalent cadmium effect in vivo on reproductive systems. Furthermore, high
      sucrose consumption and sub-acute cadmium treatment have interactive effects on
      cerebral and renal Na+/K+ -ATPase, showing that a short-term intake of high
      quantity of sucrose can aggravate the toxicity of Cd2+.

PMID- 15454310
TI  - Oltipraz, 3H-1,2-dithiole-3-thione, and sulforaphane induce overlapping and
      protective antioxidant responses in murine microglial cells.
AB  - Oltipraz (OPZ) is a known inducer of glutathione S-transferases and a mechanism
      based inhibitor of cytochrome P450 1A2. Given the detoxification characteristics
      of this compound, the transcriptional effects of OPZ, along with the related
      naturally occurring compounds 3H-1,2-dithiole-3-thione (D3T) and sulforaphane
      (SF), were examined by gene expression profiling in murine BV-2 microglial cells,
      a neuronal macrophage cell type that mediates inflammatory responses in the
      brain. We show that the three compounds generate largely overlapping
      transcriptional changes in genes that are associated with detoxification and
      antioxidant responses. In addition, induction of an antioxidant/detoxification
      response in the microglial cells by OPZ, D3T, or SF was also able to protect
      cells from H2O2 -induced toxicity and to attenuate the production of reactive
      oxygen species in response to lipopolysaccharide treatment of cells. These
      results show that OPZ, D3T, and SF activate overlapping changes in gene
      expression and that they can regulate detoxification/antioxidant responses in
      multiple cells types, including cell types known to have a role in the production
      of oxidative stress.

PMID- 15454311
TI  - Minimal influence of metallothionein over-expression on nickel carcinogenesis in
      mice.
AB  - Metallothionein (MT) is a metal-binding protein associated with tolerance to
      metals and oxidative stress. Nickel is a metal carcinogen potentially acting
      through oxidative attack on critical biomolecules. We investigated the role of MT
      in nickel carcinogenesis using MT-transgenic mice that constitutively over
      express MT-I in all tissues tested. Groups of 25 male MT-transgenic and wild type
      (C57BL/6; WT) mice received intramuscular injections of nickel subsulfide (Ni3S2)
      in both thighs at doses of 0 (control), 0.5, or 1.0 mg/site at 12 weeks of age
      and were observed for 104 weeks. Injection site tumors (ISTs; primarily
      fibrosarcomas) started occurring 45 weeks after nickel injection and IST
      incidence was similar in the WT (control - 0%, 0.5 mg/site - 20%, 1.0 mg/site -
      40%) and MT-transgenic mice (control - 0%, 0.5mg/site - 28%, 1.0mg/site - 29%.).
      At the 0.5 mg/site dose the average time to IST in MT-transgenic mice was
      approximately 13 weeks shorter than in WT mice. Spontaneous lung tumors developed
      in 25% of control WT mice but none developed in control MT-transgenic mice. A
      nickel dose-related trend for increased lung tumors occurred in MT-transgenic
      mice but not in WT mice. Thus, the over-expression of MT did not significantly
      mitigate the carcinogenic response to nickel.

PMID- 15454312
TI  - Morphological changes and oxidative stress in rat prostate exposed to a non
      carcinogenic dose of cadmium.
AB  - Cadmium chloride is an environmental toxicant implicated in human prostate
      carcinogenesis. The mechanism of its toxicity is far from fully understood. This
      study evaluates the effect of exposure to an oral non-carcinogenic dose of
      cadmium (15 ppm in drinking water for three months) on different parameters of
      the ventral prostatic lobe of normal and exposed rats. We analyzed the histology
      by optic light microscopy, activities of antioxidant enzymes (CAT, SOD, GPx and G
      6-PDH), expression of iNOS and COX-2 by Western blot, expression of MT-I, MT-II,
      IGF-I, IGF-BP5 and rtert by RT-PCR. Histological changes were found: the height
      of the cells decreased, acinar lumen were enlarged and they lost the typical
      invaginations. Lipoperoxidation was increased in the Cd group and the antioxidant
      enzymes changed their activities: SOD increased, CAT and G-6-PDH decreased and
      GPx did not show variations. iNOS and COX-2 did not change their expressions. MT
      I and IGF-BP5 mRNA increased while MT-II, IGF-I and rtert did not show
      variations. Cd exposure induces important morphological changes in the prostate,
      which could be a consequence of lipoperoxidation and oxidative stress, which are
      not related to iNOS and COX-2. The histology suggests an involution state of the
      gland, confirmed by the expression of IGF-I, IGF-BP5 and rtert.

PMID- 15454313
TI  - Monostrain, multistrain and multispecies probiotics--A comparison of
      functionality and efficacy.
AB  - This literature review was carried out to make a comparison of functionality and
      efficacy between monostrain, multistrain and multispecies probiotics. A
      monostrain probiotic is defined as containing one strain of a certain species and
      consequently multistrain probiotics contain more than one strain of the same
      species or, at least of the same genus. Arbitrarily, the term multispecies
      probiotics is used for preparations containing strains that belong to one or
      preferentially more genera. Multispecies probiotics were superior in treating
      antibiotic-associated diarrhea in children. Growth performance and particularly
      mortality in broilers could be improved with multistrain probiotics. Mice were
      better protected against S. Typhimurium infection with a multistrain probiotic. A
      multispecies probiotic provided the best clearance of E. coli O157:H7 from lambs.
      Rats challenged with S. Enteritidis showed best post-challenge weight gains when
      treated with a multispecies probiotic. Possible mechanisms underlying the
      enhanced effects of probiotic mixtures are discussed. It is also emphasized that
      strains used in multistrain and multispecies probiotics should be compatible or,
      preferably, synergistic. The design and use of multistrain and multispecies
      probiotics should be encouraged.

PMID- 15454314
TI  - The 'buttery' attribute of wine--diacetyl--desirability, spoilage and beyond.
AB  - The diketone, diacetyl, is a major flavour metabolite produced by lactic acid
      bacteria (LAB). Of the LAB associated with wine, Oenococcus oeni is encouraged
      during the malolactic (ML) fermentation, a biodeacidification of wine during
      which the metabolism of diacetyl occurs. Diacetyl, which imparts a buttery aroma
      and flavour to many fermented foods and beverages, is a key flavour compound of
      most fermented dairy products. In wine, diacetyl has important stylistic
      implications. The biosynthesis of diacetyl is dependent upon citric acid
      metabolism and diacetyl is an intermediate metabolite which can be further
      reduced to acetoin and the alcohol, 2,3-butanediol. This review will focus on the
      sensory perception, metabolism, genetics and analysis of diacetyl during wine
      production. The extensive knowledge of diacetyl metabolism in dairy LAB is used
      to enhance the understanding of diacetyl metabolism of wine LAB. Factors which
      can effect the formation and concentration of diacetyl in wine are discussed.
      These include malolactic bacterial strain, wine chemical and physical parameters
      (pH, temperature, citric acid, sulfur dioxide, aeration) and the presence of
      yeast lees. Finally, the affects of other wine components, such as phenolics, are
      discussed.

PMID- 15454315
TI  - Release of macromolecules by Saccharomyces cerevisiae during ageing of French
      flor sherry wine "Vin jaune".
AB  - The French flor sherry wine "Vin jaune" spends 6 years and 3 months in the same
      barrel under a yeast velum. Because of temperature variations in the cellars,
      this velum sinks partially into the wine and a deposit of dead yeasts cells
      accumulates in the bottom of the barrels, favouring the formation of new velum.
      Growth and autolysis occur simultaneously. This study investigated the evolution
      of macromolecules released by yeasts during the ageing of "Vin jaune" in a model
      system closely simulating winemaking. It was observed that the release of
      macromolecules during the formation of the velums by living yeasts was low but
      greatly increased when the velums fell and yeast viability decreased. The release
      of macromolecules was then due to the autolysis of dead cells. Analysis of
      macromolecules during ageing revealed that they contained 73.3-78.5% neutral
      sugars and 6-7% proteins according to the ageing stage. Their amino acid
      composition did not change during ageing. A high content of serine and threonine
      commonly involved in O-glycosidic linkages present in yeast mannoproteins was
      observed. Throughout ageing, the mannose and glucose contents of macromolecules
      increased but the ratio of polymeric mannose to glucose decreased. Size exclusion
      chromatography showed that mannoproteins released in wine were partially
      hydrolysed by yeast beta-1,3-glucanases freed in wine.

PMID- 15454316
TI  - A RAPD-based survey of thermophilic bacilli in milk powders from different
      countries.
AB  - Twenty-eight milk powders from 18 different countries were examined for the
      number and type of contaminating thermophilic bacilli. Of 742 isolates examined,
      96.8% were assigned to the same strains of bacilli as previously found in New
      Zealand powders. The dominant isolate was Anoxybacillus flavithermus strain C
      followed by Bacillus licheniformis strain F. The former was also prevalent in New
      Zealand powders and the results demonstrate that A. flavithermus represents a
      widespread contaminant, seemingly ubiquitous in factories producing milk powder.
      The presence of thermophilic strains of Geobacillus stearothermophilus and to a
      lesser extent of Bacillus subtilis in milk powders was reconfirmed.

PMID- 15454317
TI  - Characterization of lytic enzyme activities of Lactobacillus gasseri with special
      reference to autolysis.
AB  - Lactobacillus gasseri JCM 1130 and JCM 1131(T) exhibited autolytic activity in
      agar containing autoclaved cells of each strain as substrate. By zymogram
      analysis of JCM 1131(T), two lytic bands with apparent molecular masses of 54.5
      and 35 kDa, were detected. Similarly, JCM 1130 yielded two lytic bands with
      apparent molecular masses of 35 and 33.5 kDa. In simple buffers as well, JCM
      1131(T) suffered a drastic decrease in cell turbidity, but JCM 1130 did not
      undergo the decrease. The optimal pH for autolysis of JCM 1131(T) was in the
      range of 6.0-7.0, and the lysis was completely inhibited at pH 4-5. The lysis of
      JCM 1131(T) was suppressed by NaCl, in a concentration-dependent way. When
      subjected to UV irradiation or mitomycin C (MMC) treatment, cultures of both
      strains elicited conspicuous turbidity decrease after 2-4 h of growth, suggesting
      the occurrence of prophage induction. The 35-kDa lytic band of JCM 1131(T) and
      the 33.5-kDa protein of JCM 1130 were considerably increased by UV irradiation.

PMID- 15454318
TI  - Effect of treatment with Trichoderma harzianum Rifai formulated in invert
      emulsion on postharvest decay of apple blue mold.
AB  - Conidia of Trichoderma harzianum were formulated in invert emulsion (water-in-oil
      type) at a concentration of 6.0 x 10(7) conidia/ml of the formulation. Treatments
      with conidia in the formulated emulsion and conidia in sterile distilled water
      were conducted to assess the effect on Penicillium expansum Link inoculated on
      apple fruits. Comparisons were made with control treatments of an uninoculated
      emulsion and uninoculated distilled water. The T. harzianum-containing emulsion
      significantly (P <or= 0.05) reduced the decay-lesion diameter compared to the T.
      harzianum-containing water or the uninoculated emulsion or distilled water
      controls (17.5, 25.7, 34.0, and 34.2 mm, respectively). Significant differences
      (P <or= 0.05) were also obtained between means of percent reduction in decay
      lesion diameter relative to sterile distilled water control in the treatments
      with formulated and nonformulated conidia and control with uninoculated invert
      emulsion (48.8%, 24.8%, and 0.6%, respectively). Mean time period needed for
      sporulation of P. expansum was significantly (P <or= 0.05) increased when the
      treatments with formulated T. harzianum conidia were applied in comparison with
      the other types of treatments (14.2 versus 12.2, 9.0, and 8.8 days, respectively,
      for the other treatments). However, no significant differences (P <or= 0.05) were
      obtained in means of decay-lesion diameter or in means of time period needed for
      sporulation of P. expansum in the control treatments (uninoculated invert
      emulsion versus sterile distilled water). This indicates that the effect of the
      formulation ingredients on decay-lesion development of P. expansum or its
      sporulation was not significant. A significant (P <or= 0.05) long period of
      protection from P. expansum infection (up to 2 months) was also obtained when
      unwounded apple fruits were dipped for 30-s period in formulated T. harzianum
      conidia before being inoculated by P. expansum compared to the wounded fruits.
      This indicates the importance of the latter type of treatment in protecting apple
      fruits from blue mold infection for long time at postharvest stage without
      refrigeration.

PMID- 15454319
TI  - Statistical evaluation of mathematical models for microbial growth.
AB  - The aim of this study was to evaluate the suitability of several mathematical
      functions for describing microbial growth curves. The nonlinear functions used
      were: three-phase linear, logistic, Gompertz, Von Bertalanffy, Richards, Morgan,
      Weibull, France and Baranyi. Two data sets were used, one comprising 21 growth
      curves of different bacterial and fungal species in which growth was expressed as
      optical density units, and one comprising 34 curves of colony forming units
      counted on plates of Yersinia enterocolitica grown under different conditions of
      pH, temperature and CO(2) (time-constant conditions for each culture). For both
      sets, curves were selected to provide a wide variety of shapes with different
      growth rates and lag times. Statistical criteria used to evaluate model
      performance were analysis of residuals (residual distribution, bias factor and
      serial correlation) and goodness-of-fit (residual mean square, accuracy factor,
      extra residual variance F-test, and Akaike's information criterion). The models
      showing the best overall performance were the Baranyi, three-phase linear,
      Richards and Weibull models. The goodness-of-fit attained with other models can
      be considered acceptable, but not as good as that reached with the best four
      models. Overall, the Baranyi model showed the best behaviour for the growth
      curves studied according to a variety of criteria. The Richards model was the
      best-fitting optical density data, whereas the three-phase linear showed some
      limitations when fitting these curves, despite its consistent performance when
      fitting plate counts. Our results indicate that the common use of the Gompertz
      model to describe microbial growth should be reconsidered critically, as the
      Baranyi, three-phase linear, Richards and Weibull models showed a significantly
      superior ability to fit experimental data than the extensively used Gompertz.

PMID- 15454320
TI  - Effectiveness of lemon juice, vinegar and their mixture in the elimination of
      Salmonella typhimurium on carrots (Daucus carota L.).
AB  - Lemon juice, vinegar and the mixture of lemon juice and vinegar (1:1) were tested
      for their effectiveness in reducing the counts of inoculated Salmonella
      typhimurium (approximately 6 and 3 log cfu/g) on carrots. Treatment of carrot
      samples with lemon juice vinegar alone for different exposure times (0, 15, 30
      and 60 min) caused significant reductions ranging between 0.79-3.95 and 1.57-3.58
      log cfu/g, respectively, while the number of pathogens was reduced to an
      undetectable level after 30-min treatment by combined used lemon juice vinegar.

PMID- 15454321
TI  - Evidence on the role of protein biosynthesis in the induction of heat tolerance
      of Lactobacillus rhamnosus GG by pressure pre-treatment.
AB  - It was the aim of this work to evaluate, whether and to which extent heat
      resistance of Lactobacillus rhamnosus GG is affected by mild pressure treatments
      prior to exposure to lethal temperatures, such as during spray-drying. It was
      observed that cells pressure pre-treated at 100 MPa at 37 degrees C for 10 min
      showed higher survival than untreated cells when exposed to heat challenge at 60
      degrees C. To gain more insights on the cellular mode of action of pressure
      induced heat tolerance, flow cytometric analysis was applied in combination with
      functional dye LIVE/DEAD BacLight bacterial viability kit. Dot plot analysis
      showed that a lower degree of membrane damage was observed at pressure pre
      treated cells upon heat treatment at 60 degrees C for 3 min. Evaluation of heat
      inactivation kinetics of cells pressure treated in the presence of
      chloramphenicol, a protein synthesis inhibitor, pointed out the potential
      contribution of pressure-induced protein biosynthesis in the enhancement of
      bacterial heat tolerance.

PMID- 15454322
TI  - The sensitivities and specificities of total plasma protein and plasma fibrinogen
      for the diagnosis of traumatic reticuloperitonitis in cattle.
AB  - We performed a prospective clinical study to select cut-off points for total
      plasma protein (TPP) and plasma fibrinogen (PF) to differentiate between
      traumatic reticuloperitonitis (TRP) and other gastrointestinal diseases with
      similar clinical signs, and to estimate the dependence and accuracy of TPP and PF
      when used in series or in parallel. TPP and PF were estimated preoperatively by
      refractometry in 93 cattle with TRP and 65 cattle with gastrointestinal diseases
      such as vagus indigestion (n = 16), liver abscesses (n = 17), omasal impaction (n
      = 19) and Johne's disease (n = 13). Three different cut-off points were selected
      by two-graph receiver-operating characteristic (TG-ROC) analysis for TPP and PF.
      Conditional covariances were calculated as a measure of dependence between
      sensitivities and specificities of TPP and PF. The cut-off points of 7.22, 7.78
      and 8.82g/dl for TPP and 622, 691 and 766mg/dl for PF were suggested by TG-ROC
      based on different requirements of test performances. There was moderate negative
      dependence between sensitivities of TPP and PF at the 8.82g/dl and 766mg/dl cut
      off points, and mild negative dependence between their specificities at the
      7.78g/dl and 691mg/dl cut-off points, respectively. Acceptable accuracy (98 or
      86% specificity with 62 or 88% sensitivity, respectively) was obtained with
      serial interpretation of the tests.

PMID- 15454323
TI  - Spatial risk assessment of herd sero-status of Aujeszky's disease in a county in
      Hungary.
AB  - A Geographic Information System (VetEpiGIS) was used to analyze the ADV
      (Aujeszky's disease virus) sero-status in large-scale pig units regarding certain
      geographical features in a county of southern Hungary. The ADV sero-statuses were
      collected from all swine units in Csongrad county in 1998-2000. The units'
      coordinates were combined with a vector graphical digital map of the county, with
      a resolution of 1:100,000. Logistic regression tested the associations between
      sero-status of large-scale units and presence of topographical features, other
      units and villages in the neighborhood. "Neighborhood" was defined by circular
      zones with radius 1-10km around the unit (in 1km increments; one logistic
      regression for each radius). The following topographical features showed
      significant positive association with the ADV seropositivity: lake (3km OR: 5.7;
      5km OR: 7.5; 6km OR: 6.1; 10km OR: 5.4) and highway (5km OR: 4.2; 6km OR: 5.3).
      Other features had negative association with ADV seropositivity: forest (3km OR:
      0.13; 4km OR: 0.15; 5km OR: 0.15; 6km OR: 0.10; 7km OR: 0.10; 8km OR: 0.23) and
      uninfected large-scale unit (4km OR: 0.07; 5km OR: 0.27; 6km OR: 0.32; 7km OR:
      0.31).

PMID- 15454324
TI  - Participatory diagnosis of a heat-intolerance syndrome in cattle in Tanzania and
      association with foot-and-mouth disease.
AB  - A heat-intolerance (HI) syndrome in cattle in Tanzania was suspected to be
      associated with previous, clinical foot-and-mouth disease (FMD). A participatory
      appraisal (PA) method called "matrix scoring" was used to explore livestock
      keeper perceptions of association between HI and cattle diseases. A PA method
      called 'proportional piling' was used to estimate herd incidence of FMD and other
      diseases, herd incidence of HI, and association between HI and other cattle
      diseases. Use of matrix scoring and proportional piling with pastoral Maasai
      informants demonstrated association between FMD and HI. With agropastoral Sukuma
      informants, the matrix-scoring method did not indicate an association between FMD
      and HI, whereas the proportional piling method indicated a weak association.
      Results were supported by calculation of positive predictive values for herder
      diagnosis of HI and FMD. Clinical examination of cattle by veterinarians was used
      to confirm HI cases and detection of antibody to non-structural proteins of FMD
      virus was used to confirm previous clinical FMD.

PMID- 15454325
TI  - Predicted quantitative effect of logistic slaughter on microbial prevalence.
AB  - Logistic slaughter is an intervention measure intended to reduce cross
      contamination during slaughter by slaughtering contaminated units (=(groups of)
      animals) last. This paper describes a simple mathematical model which predicts
      the prevalences of contaminated units after logistic and random-order slaughter.
      The effect of logistic slaughter is the difference between these prevalences. The
      model assumes that uncontaminated units can become contaminated by contaminated
      units that were slaughtered before them; the contributions of contaminated units
      are independent. It also assumes that a slaughterhouse is uncontaminated at the
      start of the day and that a unit that is contaminated before slaughter also is
      contaminated after slaughter. The model was analysed using numerical simulations;
      for a selection of cases, analytical formulas can be derived and are presented.
      Contamination of broiler flocks with Salmonella was used as a case study. Even
      for this simple model, data availability is a problem leading to uncertain
      parameter estimates. An average cross-contamination scenario predicts that the
      beneficial effect of logistic slaughter is as low as 9.1%, which casts doubt on
      its usefulness as an intervention measure. The case study produced these general
      model results: the effect of logistic slaughter increases with the probability of
      cross-contamination between units; with the length of the slaughter queue; and
      with sensitivity (the probability of a positive test from a unit contaminated at
      the start of slaughter). However, the effect is small if the prevalence of
      contaminated units before slaughter is low or high.

PMID- 15454326
TI  - Salmonella Dublin infection in dairy cattle: risk factors for becoming a carrier.
AB  - Long-term Salmonella Dublin carrier animals harbor the pathogen in lymph nodes
      and internal organs and can periodically shed bacteria through feces or milk, and
      contribute to transmission of the pathogen within infected herds. Thus, it is of
      great interest to reduce the number of new carrier animals in cattle herds. An
      observational field study was performed to evaluate factors affecting the risk
      that dairy cattle become carrier animals after infection with Salmonella Dublin.
      Based on repeated sampling, cattle in 12 Danish dairy herds were categorized
      according to course of infection, as either carriers (n = 157) or transiently
      infected (n = 87). The infection date for each animal was estimated from fecal
      excretion and antibody responses. The relationship between the course of
      infection (carrier versus transiently infected) and risk factors were analyzed
      using a random effect multilevel, multivariable logistic regression model. The
      animals with the highest risk of becoming carriers were heifers infected between
      the age of 1 year and 1st calving, and cows infected around the time of calving.
      The risk was higher in the first two quarters of the year (late Winter to
      Spring), and when the prevalence of potential shedders in the herd was low. The
      risk also varied between herds. The herds with the highest risk of carrier
      development were herds with clinical disease outbreaks during the study period.
      These findings are useful for future control strategies against Salmonella
      Dublin, because they show the importance of optimized calving management and
      management of heifers, and because they show that even when the herd prevalence
      is low, carriers are still being produced. The results raise new questions about
      the development of the carrier state in cattle after infection with low doses of
      Salmonella Dublin.

PMID- 15454327
TI  - Risk factors for the herd-level bacteriologic prevalence of Salmonella in Belgian
      slaughter pigs.
AB  - Herd-level risk factors for salmonellosis in pigs were investigated in a cross
      sectional study on 62 Belgian farrow-to-finish pig herds belonging to one
      slaughterhouse cooperative. Data concerning housing and ventilation, management,
      hygiene, biosecurity, production parameters, feeding, disease control and
      transport to the slaughterhouse were collected during a herd visit by means of a
      questionnaire. The percentage of positive animals in a slaughterhouse delivery,
      as determined by qualitative Salmonella isolation in the mesenteric lymph nodes
      taken from 30 slaughter pigs, was the outcome variable. All samples were taken in
      4 different slaughterhouses. Variables first were submitted to a univariable
      analysis using a logistic mixed regression model, with herd as random effect.
      Variables which were related to the Salmonella prevalence (P < 0.05) were
      analysed further in a multivariable model. The clustering of Salmonella infection
      within a pen also was studied in a generalised mixed model with pen as random
      effect. Salmonella isolates were identified by serotype. In 57 (92%) of the
      herds, at least one sample was found positive for Salmonella. The median
      percentage of positive Salmonella samples per delivery was 64% (range: 0-100%).
      In the multivariable model, only type of floor was related significantly to the
      prevalence: 100% (95% CI 88-100) for herds with <50% slatted floors to 54% (36
      70) for herds with fully slatted floors. The results from the analysis should be
      interpreted with care because only 62 herds were included in the study.
      Clustering between pigs from the same pen could not be demonstrated (variance +/-
      S.D.: 0.11 +/- 0.16). S. typhimurium (30%) and S. derby (20%) were most common
      among the 23 different serotypes that were found.

PMID- 15454328
TI  - Comparison of management practices between Ohio, USA dairy farms participating in
      whole-herd Johne's disease testing programs and those not participating.
AB  - The purpose of our mail survey was to compare the adoption of management
      practices recommended for Johne's disease (JD) control between herds involved in
      whole-herd testing programs versus those that do not routinely test the entire
      herd for JD. A questionnaire consisted of 38 closed-ended questions that inquired
      about: general herd characteristics; management practices related to JD control;
      changes that occurred within the last 5 years regarding management practices
      recommended for the control of JD; producer knowledge of JD; the perceived
      infection status of the herd by the producer; and herd JD-testing history. The
      questionnaire was mailed to 810 Ohio dairy producers in September 2002; 266
      questionnaires were returned (32.8% response). We used univariable logistic
      regression models to assess the relationship between whole-herd testing status
      (TESTING versus NON-TESTING) and each management practice, each change in
      management practice and producer knowledge about JD. Because it is conceivable
      that only producers who believe their herds to be infected would be motivated to
      adopt the management practices recommended for control of JD, the comparisons
      were repeated with models that controlled for producer-perceived infection
      status. Of the 20 management practices recommended for JD control that we
      evaluated, 7 differed between TESTING and NON-TESTING herds. Additionally,
      TESTING herds more-frequently reported adopting changes within the past 5 years
      relative to NON-TESTING herds with respect to 7 of 9 management practices
      evaluated. Producers with TESTING herds also reported greater familiarity with JD
      than those with NON-TESTING herds.

PMID- 15454329
TI  - Herd-level seroprevalence and risk-mapping of bovine hypodermosis in Belgian
      cattle herds.
AB  - Our objective was to determine the seroprevalence of Hypoderma spp. and to
      develop a spatial model describing the risk surface of warble-fly infection in
      Belgian cattle herds (adjusting for herd size, herd type, local temperature,
      rainfall, relative air humidity and land-cover). This survey was carried out in
      390 selected herds of all types (dairy, mixed and beef) from December 1997 to
      March 1998, which were included in a national infectious bovine rhinotracheitis
      and paratuberculosis (Johne's-disease) survey. All animals >24 months old were
      blood sampled and an ELISA was used on pooled serum samples (10 animals per
      pool). The herd seroprevalence was 48.7% (95% confidence interval: 43.6-53.8);
      positive herds were mainly in the south of the country and along the North Sea
      coast. The logistic multiple-regression model of herd-level seropositivity
      indicated that mixed-type and beef-cattle herds have more than four-fold and two
      fold increases in the odds of being Hypoderma-positive, respectively, compared
      with dairy herds.

PMID- 15454330
TI  - Vaccination coverage and epidemiological parameters of the owned-dog population
      in Thungsong District, Thailand.
AB  - Canine rabies vaccination is delivered in Thungsong District, Thailand, as an
      annual campaign between March 1 and 31, and also at other times through private
      veterinary clinics, para-veterinarians and health-care staff residing in the
      villages. The current questionnaire-interview survey was conducted between June
      23 and July 18, 2002 to determine: rabies-vaccination coverage amongst the owned
      dog population; basic dog-population information; and community awareness about
      rabies. The modified expand programme on immunization cluster-survey method was
      used to collect information about dog demography and management characteristics.
      Household knowledge about rabies and sources of rabies information were assessed.
      Vaccinated dogs were identified from vaccine certificates or owner reports
      confirmed by vaccinators. Seventy percent (95%CI 62-78) of 364 eligible owned
      dogs were vaccinated within the 6 months prior to data collection. Of these 255
      vaccinated dogs, 44, 21, 13, 17 and 5% were vaccinated through the annual
      vaccination campaign, veterinary clinics, para-veterinarians, other vaccinators
      and owners, respectively. Fifty-four percent of households owned dogs. The sex
      ratio in dogs was 2 males per female; the dog: human ratio was 1: 4.6 with an
      average of 0.9 dogs per household (1.7 dogs per dog-owning household). Most dogs
      roamed freely and these were less likely to be vaccinated compared to dogs being
      kept on premises or on a leash. Almost all households were aware of rabies and
      the need for dog rabies vaccination as a control method. Seventy-six percent
      believed that rabies only occurred in summer. There was little awareness about
      cat rabies amongst households. Vaccination coverage in the total dog population
      clearly has not yet reached the 80% target level set by Thailand's official
      rabies-control programme. Improved effectiveness of the owned-dog rabies
      vaccination campaigns in each community is needed-perhaps by more community
      education about dog management or by better management of ownerless dogs.

PMID- 15454331
TI  - Leptospiral infection and seropositivity in rodents.

PMID- 15454333
TI  - Ontogenetic migration of the mental foramen in Neandertals and modern humans.
AB  - Since the nineteenth century, researchers have noted that Neandertal and modern
      human adults differ in mental foramen position, although the ontogenetic changes
      in the position of this feature have only recently come under the scrutiny of
      paleoanthropologists. Research on mental foramen position has focused on whether
      this feature is inferior to a particular tooth. However, tooth position may not
      be a reliable indicator of mental foramen position because of variability in
      tooth size within and between taxa and during eruption events. As opposed to
      observing the mental foramen with respect to the postcanine teeth, we examined
      linear distances from the mental foramen to other mandibular landmarks. Modern
      human adults may appear truncated, or paedomorphic, in mental foramen position
      with respect to Neandertal adults. However, infants of the two taxa differ
      substantially in anterior mandibular form. The initial differences in the shape
      of the mental region may be related to the embryological position of the mental
      foramen in modern humans and its role in the development of the mental trigone.
      The shape changes that accrue thereafter, possibly from faster mandibular growth
      rates in Neandertals, further distinguish the adults from one another. Although
      mandibular shape differences exist from early infancy onwards, adults of the two
      taxa are broadly similar in bi-mental foramen breadth with respect to mandibular
      size. For this reason, qualitative assessments of mental foramen position may
      provide less taxonomic information than previously thought.

PMID- 15454334
TI  - Estimating human long bone cross-sectional geometric properties: a comparison of
      noninvasive methods.
AB  - Cross-sectional properties (areas, second moments of area) have been used
      extensively for reconstructing the mechanical loading history of long bone
      shafts. In the absence of a fortuitous break or available computed tomography
      (CT) facilities, the endosteal and/or periosteal boundaries of a bone may be
      approximated using alternative noninvasive methods. The present study tests
      whether cross-sectional geometric properties of human lower limb bones can be
      adequately estimated using two such techniques: the ellipse model method (EMM),
      which uses biplanar radiography alone, and the latex cast method (LCM), which
      involves molding of the subperiosteal contour in combination with biplanar
      radiography to estimate the contour of the medullary canal. Results of both
      methods are compared with "true" cross-sectional properties calculated by direct
      sectioning. The study sample includes matched femora and tibiae of 50 Pecos
      Pueblo Amerindians. Bone areas and second moments of area were calculated for the
      midshaft femur and tibia and proximal femoral diaphysis in each individual.
      Percent differences between methods were derived to evaluate directional
      (systematic) and absolute (random) error. Multiple regression was also used to
      investigate the sources of error associated with each method. The results
      indicate that while the LCM shows generally good correspondence to the true cross
      sectional properties, the EMM generally overestimates true parameters. Regression
      equations are provided to correct this overestimation, and, when applied to
      another sample, are shown to significantly improve estimates for the femoral
      midshaft, although corrections are less successful for the other section
      locations. Our results suggest that the LCM is an adequate substitute for
      estimating cross-sectional properties when direct sectioning and CT are not
      feasible. The EMM is a reasonable alternative, although the bias inherent in the
      method should be corrected if possible, especially when the results of the study
      are to be compared with data collected using different methods.

PMID- 15454335
TI  - Influences of limb proportions and body size on locomotor kinematics in
      terrestrial primates and fossil hominins.
AB  - During locomotion, mammalian limb postures are influenced by many factors
      including the animal's limb length and body mass. Polk (2002) compared the gait
      of similar-sized cercopithecine monkeys that differed limb proportions and found
      that longer-limbed monkeys usually adopt more extended joint postures than
      shorter-limbed monkeys in order to moderate their joint moments. Studies of
      primates as well as non-primate mammals that vary in body mass have demonstrated
      that larger animals use more extended limb postures than smaller animals. Such
      extended postures in larger animals increase the extensor muscle mechanical
      advantage and allow postures to be maintained with relatively less muscular
      effort (Polk, 2002; Biewener 1989). The results of these previous studies are
      used here to address two anthropological questions. The first concerns the
      postural effects of body mass and limb proportion differences between
      australopithecines and members of the genus Homo. That is, H. erectus and later
      hominins all have larger body mass and longer legs than australopithecines, and
      these anatomical differences suggest that Homo probably used more extended
      postures and probably required relatively less muscular force to resist gravity
      than the smaller and shorter-limbed australopithecines. The second question
      investigates how animals with similar size but different limb proportions differ
      in locomotor performance. The effects of limb proportions on gait are relevant to
      inferring postural and locomotor differences between Neanderthals and modern Homo
      sapiens which differ in their crural indices and relative limb length. This study
      demonstrates that primates with relatively long limbs achieve higher walking
      speeds while using lower stride frequencies and lower angular excursions than
      shorter-limbed monkeys, and these kinematic differences may allow longer-limbed
      taxa to locomote more efficiently than shorter-limbed species of similar mass.
      Such differences may also have characterized the gait of Homo sapiens in
      comparison to Neanderthals, but more experimental data on humans that vary in
      limb proportions are necessary in order to evaluate this question more
      thoroughly.

PMID- 15454336
TI  - Human size evolution: no evolutionary allometric relationship between male and
      female stature.
AB  - In many animal groups, sexual size dimorphism tends to be more pronounced in
      species with large body size. Similarly, in a previous cross-cultural analysis,
      male and female stature in humans were shown to be positively allometrically
      related, indicating a similar relationship where populations with larger stature
      were more dimorphic. In this study, we re-examine the hypothesis of an allometric
      relationship between the sexes using phylogenetic methodology. First, however, we
      tested whether there exist phylogenetic signals in male and female stature. Data
      on mean stature from 124 human populations was gathered from the literature. A
      phylogenetic test showed that male and female stature were significantly
      associated with phylogeny. These results indicate that comparative methods that
      to some degree incorporate genetic relatedness between populations are crucial
      when analyzing human size evolution in a cross-cultural context. Further, neither
      non-phylogenetic nor phylogenetic analyses revealed any allometric relationship
      between male and female stature. Thus, we found no support for the idea that
      sexual dimorphism increases with increasing stature in humans.

PMID- 15454337
TI  - Occurrence of Theropithecus sp. in the Late Villafranchian of Southern Italy and
      implication for Early Pleistocene "out of Africa" dispersals.
AB  - Three cervical vertebrae of a large primate have been identified in the revision
      of the faunal assemblage collected during the late '70s from fissure fillings in
      the area known as Pirro Nord in southern Italy. By size the three vertebrae are
      comparable to the large fossil species Theropithecus oswaldi, however we prefer
      here to attribute the remains to Theropithecus sp. The Pirro Nord Theropithecus
      represents the second finding outside of Africa of this genus in association with
      Megantereon whitei, after the site of 'Ubeidiya. The biochronology of Pirro Nord
      faunal assemblage demonstrates that the arrival into Europe of Theropithecus
      occurred earlier than thought: in the range of approx 1.6-1.3 Ma. The
      identification of an European "African assemblage" (Theropithecus associated with
      Megantereon whitei) has consequences for interpretation of an "out of Africa"
      (genus Homo) event around the Plio-Pleistocene transition.

PMID- 15454338
TI  - Protective effects of SP600125 a new inhibitor of c-jun N-terminal kinase (JNK)
      and extracellular-regulated kinase (ERK1/2) in an experimental model of cerulein
      induced pancreatitis.
AB  - Extracellular regulated kinases (ERK1/2) and c-Jun N-terminal Kinases (JNK), are
      generally considered to play a key role in signal transduction pathways activated
      by a wide range of stimuli. We studied the effects of SP600125, a novel inhibitor
      of both JNK and ERK1/2, in male C57/BL6 mice given with an hyper-stimulating dose
      of cerulein (50 microg/kg for each of four injections at hourly intervals) to
      elicit secretagogue-induced pancreatitis. A control group received four intra
      peritoneal injections of 0.9% saline at hourly intervals. Animals were randomized
      to receive either SP600125 (15 mg/kg i.p. administered 2 h before and 30 min
      after the first injection of cerulein) or its vehicle (1 ml/kg of a 10% DMSO/NaCl
      solution). A group of animals was killed 30 minutes after the last cerulein
      injection to evaluate pancreatic JNK and ERK1/2 activation by Western Blot
      analysis. Another group was sacrificed 2 hours after the last cerulein injection
      to evaluate serum lipase and amylase levels, pancreas oedema, pancreatic content
      of Tumor Necrosis Factor-alpha (TNF-alpha) and Intercellular adhesion molecule-1
      (ICAM-1) and the histological alterations. SP600125 inhibited almost totally JNK
      activation (90%) and partially ERK1/2 activation (45%), reduced the serum lipase
      and amylase levels and the degree of oedema, blunted the increased pancreatic
      content of TNF-alpha and ICAM-1 and protected against the histological damage.
      Our data confirm that both JNK and ERK1/2 activation plays a key role in acute
      pancreatitis and that SP600125 may represent a potential therapeutic approach to
      the treatment of patients at high risk of developing this life-threatening
      condition.

PMID- 15454339
TI  - Clinical studies on the effect of Neem (Azadirachta indica) bark extract on
      gastric secretion and gastroduodenal ulcer.
AB  - We have shown earlier that Neem (Azadirachta indica) bark aqueous extract has
      potent antisecretory and antiulcer effects in animal models and has no
      significant adverse effect (Bandyopadhyay et al., Life Sciences, 71, 2845-2865,
      2002). The objective of the present study was to investigate whether Neem bark
      extract had similar antisecretory and antiulcer effects in human subjects. For
      this purpose, a group of patients suffering from acid-related problems and
      gastroduodenal ulcers were orally treated with the aqueous extract of Neem bark.
      The lyophilised powder of the extract when administered for 10 days at the dose
      of 30 mg twice daily caused a significant (p < 0.002) decrease (77%) in gastric
      acid secretion. The volume of gastric secretion and its pepsin activity were also
      inhibited by 63% and 50%, respectively. Some important blood parameters for organ
      toxicity such as sugar, urea, creatinine, serum glutamate oxaloacetate
      transaminase, serum glutamate pyruvate transaminase, albumin, globulin,
      hemoglobin levels and erythrocyte sedimentation rate remained close to the
      control values. The bark extract when taken at the dose of 30-60 mg twice daily
      for 10 weeks almost completely healed the duodenal ulcers monitored by barium
      meal X-ray or by endoscopy. One case of esophageal ulcer (gastroesophageal reflux
      disease) and one case of gastric ulcer also healed completely when treated at the
      dose of 30 mg twice daily for 6 weeks. The levels of various blood parameters for
      organ toxicity after Neem treatment at the doses mentioned above remained more or
      less close to the normal values suggesting no significant adverse effects. Neem
      bark extract thus has therapeutic potential for controlling gastric
      hypersecretion and gastroesophageal and gastroduodenal ulcers.

PMID- 15454340
TI  - Fas/CD95 is associated with glucocorticoid-induced osteocyte apoptosis.
AB  - Prolonged use of glucocorticoids is associated with decreased bone formation,
      increased resorption and osteonecrosis, through direct and indirect effects on
      the activity and viability of bone effector cells, osteoblasts and osteoclasts,
      and osteocytes. This study has investigated molecular pathways implicated in
      Dexamethasone-induced apoptosis of osteocytes, using a cell line and primary
      chicken cells. MLO-Y4 osteocytes were pre-treated with several bisphosphonates
      representing a range of anti-resorptive activities and conformation/structure
      relationships, and were subsequently challenged with Dexamethasone. Apoptotic
      cells were detected at various times after treatment using morphological and
      biochemical criteria. Dex was shown to induce apoptosis associated with the
      Fas/CD95 death receptor and in a caspase 8 dependent manner. The apoptotic
      response was inhibited by all variants of the BP molecules, including those with
      reduced anti-resorptive activity, indicating that Dex-induced apoptosis is
      independent of anti-osteoclastic activity. Dex-induced apoptosis was associated
      with a transient increase in phosphorylated ERK 1/2 and was blocked by the ERK
      inhibitor UO126. In addition, both UO126 and BPs decreased localization of Fas to
      the cell membrane. ERK activation by PMA did not induce death or Fas
      upregulation, suggesting that Fas may be important for the induction of apoptosis
      and the existence of an additional factor activated by Dex which enables the
      cooperation between the Dex-activated ERK and Fas pathways, during apoptosis of
      osteocytes. Furthermore, upregulation of death and Fas was not accompanied by
      upregulation of FasL, pointing to the possible existence of FasL-independent Fas
      associated death in these cells.

PMID- 15454341
TI  - Effects of leptin and neuropeptide-Y on transcript levels of thyrotropin beta and
      common alpha subunits of rat pituitary cells in vitro.
AB  - Leptin and neuropeptide-Y (NPY) are indicated to play a role in hypothalamo
      pituitary-thyroid (HPT) axis in relation to regulation of energy homeostasis
      mediated through acting at hypothalamic synthesis and release of thyrotropin
      (TSH)-releasing hormone (TRH). Whether leptin and NPY also act at pituitary level
      in HPT axis remains unknown. This study aimed at investigating whether or not
      leptin and NPY exert actions at pituitary in modulation of transcript levels of
      TSHbeta and the common pituitary glycoprotein hormone alpha (PGHalpha) subunits.
      The dispersed pituitary cells from 6 wk old male Wistar rats were incubated with
      or without TRH, leptin or NPY of 10(-8) M and 10(-10) M for 6 h at 37 degrees C
      in medium-199 under aeration of 95% O2 and 5% CO2. The mRNA levels of TSHbeta and
      PGHalpha subunits of the incubated cells were measured by reverse transcription
      polymerase chain reaction. The results revealed that leptin stimulated, while NPY
      inhibited, TSHbeta mRNA levels in a dose-related manner. Both leptin and NPY
      increased alpha subunit mRNA levels. It is demonstrated for the first time that
      both leptin and NPY exert a direct action at rat pituitary affecting steady-state
      levels of mRNA of TSHbeta and PGHalpha subunits. The present study supports that
      both leptin and NPY act at the pituitary as well besides the hypothalamus in HPT
      axis in relation to regulation of energy homeostasis.

PMID- 15454342
TI  - Induction of HL-60 apoptosis by ethyl acetate extract of Cordyceps sinensis
      fungal mycelium.
AB  - The cultivated mycelium of a Cordyceps sinensis (Cs) fungus was sequentially
      extracted by petroleum ether, ethyl acetate (EtOAc), ethanol and water. The EtOAc
      extract showed the most potent cytotoxic effect against the proliferation of
      human premyelocytic leukemia cell HL-60, with an ED50 < or = 25 microg/ml for 2
      day treatment. The EtOAc extract induced the characteristic apoptotic symptoms in
      the HL-60 cells, DNA fragmentation and chromatin condensation, occurring within 6
      8 h of treatment at a dose of 200 microg/ml. The activation of caspase-3 and the
      specific proteolytic cleavage of poly ADP-ribose polymerase were detected during
      the course of apoptosis induction. These results suggest that the Cs mycelium
      extract inhibited the cancer cell proliferation by inducing cell apoptosis.

PMID- 15454343
TI  - Link between free radicals and protein kinase C in glucose-induced alteration of
      vascular dilation.
AB  - Development of vascular complications in diabetes has been linked to the quality
      of glucose regulation and characterized by endothelial dysfunction. The exact
      mechanism behind vascular complications in diabetes is poorly understood.
      However, alteration of nitric oxide (NO) biosynthesis or bioactivity is strongly
      implicated and the mechanism behind such alterations is still a subject for
      research investigations. In the present study, we tested the hypothesis that
      glucose-induced attenuation of vascular relaxation involves protein kinase C
      (PKC)-linked generation of free radicals. Vascular relaxation to acetylcholine
      (ACh; 10(-9)-10(-5) M), isoproterenol (10(-9)-10(-5) M), or NO donor, sodium
      nitropruside (SNP; 10(-9)-10(-6) M) was determined in phenylephrine (PE, 10(-7)
      M) pre-constricted aortic rings from Sprague-Dawley rats in the presence or
      absence of 30 mM glucose (30 min), L-nitro-arginine methyl ester (L-NAME; 10(-4)
      M for 15 min), a NO synthase inhibitor, or xanthine (10(-5) M), a free radical
      generator. ACh dose-dependently caused relaxation that was attenuated by L-NAME,
      glucose, or xanthine. Pre-incubation (15 min) of the rings with vitamin C (10(-4)
      M), an antioxidant or calphostin C (10(-6) M), a PKC inhibitor, restored the ACh
      responses. However, high glucose had no significant effects on SNP or
      isoproterenol-induced relaxation. ACh-induced NO production by aortic ring was
      significantly reduced by glucose or xanthine. The reduced NO production was
      restored by pretreatment with vitamin C or calphostin C in the presence of
      glucose, but not xanthine. These data demonstrate that oxidants or PKC contribute
      to glucose-induced attenuation of vasorelaxation which could be mediated via
      impaired endothelial NO production and bioavailability. Thus, pathogenesis of
      glucose-induced vasculopathy involves PKC-coupled generation of oxygen free
      radicals which inhibit NO production and selectively inhibit NO-dependent
      relaxation.

PMID- 15454344
TI  - In vivo identification and characterization of binding sites for selective
      serotonin reuptake inhibitors in mouse brain.
AB  - The present study was undertaken to identify and characterize in vivo binding
      sites of selective serotonin reuptake inhibitors (SSRIs) in the mouse brain by
      using [3H]paroxetine as radioligand. Relatively higher concentration of
      [3H]paroxetine was detected in the whole brain (minus cerebellum) than in the
      plasma of mice after the i.v. injection of the radioligand, and the half-life
      (t1/2) of elimination was much slower. The in vivo specific [3H]paroxetine
      binding in the mouse brain after the i.v. injection was defined as the difference
      of particulate-bound radioactivity between the whole brain and cerebellum, and it
      was dose-dependently attenuated by oral or intraperitoneal administration of
      fluoxetine (8.68-116 micromol/kg). Furthermore, oral administration of
      fluvoxamine, fluoxetine, paroxetine and sertraline at the pharmacologically
      relevant doses reduced significantly (25-94%) in vivo specific [3H]paroxetine
      binding in the cerebral cortex, striatum, hippocampus, thalamus and midbrain of
      mice, and their significant decreases were observed up to at least 8 h
      (fluvoxamine), 24 h (fluoxetine), and 12 h (paroxetine and sertraline) later. The
      value of area under the curve (AUC) for decrease in [3H]paroxetine binding vs.
      time in each brain region was largest for fluoxetine among these SSRIs, due to
      the relatively longer-lasting occupation of brain serotonin transporter. The AUC
      value in mouse brain after oral administration of each SSRI was 1.2-3.2 times
      greater in the thalamus and midbrain than in the cerebral cortex, striatum and
      hippocampus. Thus, the present study has revealed that [3H]paroxetine may be a
      suitable radioligand for in vivo characterization of brain binding sites and
      pharmacological effects of SSRIs.

PMID- 15454345
TI  - Inhibitory effects of TRK-820 on systemic skin scratching induced by morphine in
      rhesus monkeys.
AB  - The inhibitory effects of kappa-opioid receptor agonists on systemic skin
      scratching induced by the intravenous administration of morphine, a micro-opioid
      receptor agonist, were investigated in rhesus monkeys. Intravenous pretreatment
      with kappa-opioid receptor agonists, either TRK-820 at 0.25 and 0.5 microg/kg or
      U-50488H at 64 and 128 microg/kg, inhibited systemic skin scratching induced by
      morphine at 1 mg/kg, i.v. in a dose-dependent manner. By the intragastric route,
      apparent inhibitory effects on morphine-induced systemic skin scratching were
      evident following pretreatment with TRK-820 at 4 microg/kg but not with U-50488H
      from 512 to 2048 microg/kg. These results suggest that TRK-820 produces
      antipruritic effects on i.v. morphine-induced systemic skin scratching and is
      more readily absorbed intragastrically than is U-50488H, resulting in high
      bioavailability in the intragastric route.

PMID- 15454346
TI  - The role of endogenous cannabinoids in the hypothalamo-pituitary-adrenal axis
      regulation: in vivo and in vitro studies in CB1 receptor knockout mice.
AB  - Exogenous cannabinoids affect multiple hormonal systems including the hypothalamo
      pituitary-adrenocortical (HPA) axis. These data suggest that endogenous
      cannabinoids are also involved in the HPA control; however, the mechanisms
      underlying this control are poorly understood. We assessed the role of endogenous
      cannabinoids in the regulation of the HPA-axis by studying CB1 receptor knockout
      (KO) and wild type (WT) mice. Basal and novelty stress-induced plasma levels of
      adrenocorticotropin (ACTH) and corticosterone were higher in CB1-KO than in WT
      mice. We investigated the involvement of the pituitary in the hormonal effects of
      CB1 gene disruption by studying the in vitro release of ACTH from anterior
      pituitary fragments using a perifusion system. Both the basal and corticotropin
      releasing hormone (CRH)-induced ACTH secretion were similar in CB1-KO and WT
      mice. The synthetic glucocorticoid, dexamethasone suppressed the CRH-induced ACTH
      secretion in both genotypes; thus, the negative feedback of ACTH secretion was
      not affected by CB1 gene disruption. The cannabinoid agonist, WIN 55,212-2 had no
      effects on basal and CRH-stimulated ACTH secretion by anterior pituitary slices.
      In our hands, the disruption of the CB1 gene lead to HPA axis hyperactivity, but
      the pituitary seems not to be involved in this effect. Our data are consistent
      with the assumption that endogenous cannabinoids inhibit the HPA-axis via
      centrally located CB1 receptors, however the understanding of the exact
      underlying mechanism needs further investigation.

PMID- 15454347
TI  - Reflective and impulsive determinants of social behavior.
AB  - This article describes a 2-systems model that explains social behavior as a joint
      function of reflective and impulsive processes. In particular, it is assumed that
      social behavior is controlled by 2 interacting systems that follow different
      operating principles. The reflective system generates behavioral decisions that
      are based on knowledge about facts and values, whereas the impulsive system
      elicits behavior through associative links and motivational orientations. The
      proposed model describes how the 2 systems interact at various stages of
      processing, and how their outputs may determine behavior in a synergistic or
      antagonistic fashion. It extends previous models by integrating motivational
      components that allow more precise predictions of behavior. The implications of
      this reflective-impulsive model are applied to various phenomena from social
      psychology and beyond. Extending previous dual-process accounts, this model is
      not limited to specific domains of mental functioning and attempts to integrate
      cognitive, motivational, and behavioral mechanisms.

PMID- 15454348
TI  - The individual within the group: balancing the need to belong with the need to be
      different.
AB  - Many theorists have wrestled with the notion of how people balance their need to
      be included in social groups with their need to be different and distinctive.
      This question is particularly salient to researchers from the social identity
      perspective, who have traditionally viewed individual differentiation within
      groups as being inimical to group identification. In this article we present a
      number of strategies that people can use to balance their need to belong and
      their need to be different, without violating social identity principles. First,
      drawing from optimal distinctiveness theory, we discuss 4 ways in which the need
      for belonging and the need to be different can be resolved by maximizing group
      distinctiveness. We then discuss 4 ways in which it is possible to achieve
      individual differentiation within a group at the same time demonstrating group
      identification. These strategies are discussed and integrated with reference to
      recent empirical research and to the social identity perspective.

PMID- 15454349
TI  - PERSON: a general model of interpersonal perception.
AB  - A general theoretical model of interpersonal perception called PERSON
      (personality, error, residual, stereotype, opinion, and norm) is developed. This
      model reparameterizes a weighted-average model (WAM; Kenny, 1991; Kenny,
      Albright, Malloy, & Kashy, 1994) into six components. Two of those components
      refer to categorical information and 4 to behavioral information. Based on a
      formal model, for which parameters are estimated from previous research studies,
      several implications are developed. The PERSON model can explain the low level of
      consensus in person perception, the fact that consensus does not increase with
      greater acquaintance, the strong stability of interpersonal judgment, the
      overconfidence effect, and the fact that short-term judgments are sometimes as
      accurate as long-term judgments. The PERSON model generally predicts that
      acquaintance is not as important in person perception as generally thought.

PMID- 15454350
TI  - A conceptual review of decision making in social dilemmas: applying a logic of
      appropriateness.
AB  - Despite decades of experimental social dilemma research, "theoretical integration
      has proven elusive" (Smithson & Foddy, 1999, p. 14). To advance a theory of
      decision making in social dilemmas, this article provides a conceptual review of
      the literature that applies a "logic of appropriateness" (March, 1994) framework.
      The appropriateness framework suggests that people making decisions ask
      themselves (explicitly or implicitly), "What does a person like me do in a
      situation like this? " This question identifies 3 significant factors:
      recognition and classification of the kind of situation encountered, the identity
      of the individual making the decision, and the application of rules or heuristics
      in guiding behavioral choice. In contrast with dominant rational choice models,
      the appropriateness framework proposed accommodates the inherently social nature
      of social dilemmas, and the role of rule and heuristic based processing.
      Implications for the interpretation of past findings and the direction of future
      research are discussed.

PMID- 15454351
TI  - It's beyond my control: a cross-temporal meta-analysis of increasing externality
      in locus of control, 1960-2002.
AB  - Two meta-analyses found that young Americans increasingly believe their lives are
      controlled by outside forces rather than their own efforts. Locus of control
      scores became substantially more external (about.80 standard deviations) in
      college student and child samples between 1960 and 2002. The average college
      student in 2002 had a more external locus of control than 80% of college students
      in the early 1960s. Birth cohort/time period explains 14% of the variance in
      locus of control scores. The data included 97 samples of college students (n =
      18,310) and 41 samples of children ages 9 to 14 (n = 6,554) gathered from
      dissertation research. The results are consistent with an alienation model
      positing increases in cynicism, individualism, and the self-serving bias. The
      implications are almost uniformly negative, as externality is correlated with
      poor school achievement, helplessness, ineffective stress management, decreased
      self-control, and depression.

PMID- 15454352
TI  - Supplemental beta-carotene, smoking, and urinary F2-isoprostane excretion in
      patients with prior early stage head and neck cancer.
AB  - Supplemental beta-carotene has been shown to increase lung cancer risk in recent
      chemoprevention trials, especially in current smokers. Several possible
      mechanisms for this effect have been suggested based upon in vitro and animal
      studies, but mechanistic data from human studies to explain the excess risk are
      lacking. beta-Carotene has both antioxidant and prooxidant effects in vitro;
      therefore, we evaluated whether or not high-dose supplemental beta-carotene might
      have prooxidant effects in vivo, especially in current smokers taking high-dose
      supplemental beta-carotene for several years (median 4.0 yr). Urine samples (n =
      55 total) were collected from both smokers and nonsmokers participating in a
      multiyear randomized chemoprevention trial of supplemental beta-carotene (50
      mg/day) versus placebo. Samples were analyzed by GC/MS for total isoprostanes and
      for 8-iso-prostaglandin F2 (8-iso-PGF2), stable end products of lipid
      peroxidation in vivo. Smokers had higher levels of both total isoprostanes and 8
      iso-PGF2. Smokers and nonsmokers randomized to beta-carotene had nonsignificantly
      lower concentrations of total isoprostanes and of 8-iso-PGF2 [mean +- SD 8-iso
      PGF2/ml = 2.00 +- 1.72 (placebo smoker); 1.72 +- 1.66 (beta-carotene smoker);
      1.22 +- 0.68 (placebo nonsmoker); 0.97 +- 0.62 (beta-carotene nonsmoker)]. These
      results indicate that supplemental beta-carotene, even when given at high doses
      for many years, does not have prooxidant effects in either smokers or nonsmokers,
      as measured by urinary excretion of F2-isoprostanes.

PMID- 15454353
TI  - RE-AIM: evidence-based standards and a Web resource to improve translation of
      research into practice.
AB  - BACKGROUND: Health services data indicate that under present conditions evidence
      based medical and preventive practices are not consistently implemented in
      clinical practice and affect the quality of care provided to patients. Operating
      with similar conditions and resources, it is unlikely that evidence-based
      behavioral medicine (EBBM) practices will be more successfully implemented.
      PURPOSE: In this article we propose ways to help improve the implementation of
      EBBM practice. METHODS: This article describes the RE-AIM (Reach,
      Efficacy/Effectiveness, Adoption, Implementation, and Maintenance) framework that
      is available on a free-use Web site (http://www.re-aim.org), which offers
      practical research translation tools, resources, and support for program
      planners, community leaders, and researchers. The material located at www.re
      aim.org can be used to help anticipate and overcome likely barriers to
      dissemination and to estimate eventual public health impact. RESULTS: Data on Web
      site utilization and lessons learned thus far in its implementation are
      presented. CONCLUSIONS: Scientists and public health leaders should devote
      greater attention to reporting practice-oriented issues such as generalizability,
      breadth of application, and pragmatic and setting or contextual issues in
      addition to the current focus on internal validity issues. We hope that this and
      similar efforts will assist EBBM interventions to have broader applications, be
      consistently implemented, and be sustained.

PMID- 15454354
TI  - Research to practice: international dissemination of evidence-based behavioral
      medicine.
AB  - BACKGROUND: In recent years, there has been a dramatic rise in the global
      prevalence of chronic conditions. Cancer, diabetes, cardiovascular diseases
      chronic lung disorders, and their common behavioral risk factors are escalating
      rapidly in developing countries, many of which are still struggling with
      infectious diseases and poor health system infrastructures. PURPOSE: This article
      examines the role that behavioral medicine can play to improve global health.
      METHODS: The World Health Organization's Innovative Care for Chronic Conditions
      Framework provides a model for identifying areas for behavioral medicine
      influence, including patient-provider interactions, organization of health care,
      community mobilization, and national policy and financing. RESULTS: Behavioral
      medicine has a large role to play in international health. Examples from around
      the world are provided. CONCLUSIONS: Because behavior is the product of
      multilevel, multifactoral determinants, there are many areas of influence for
      behavioral medicine specialists who want to contribute to global health. By
      focusing attention internationally, with special attention toward the needs of
      developing countries, the field of behavioral medicine will be not only
      responding to its global responsibilities but also repositioning itself to be
      increasingly relevant for the 21st century.

PMID- 15454355
TI  - Physical activity, cardiovascular disease, and medical expenditures in U.S.
      adults.
AB  - BACKGROUND: Physical inactivity is an established independent risk factor for
      cardiovascular disease (CVD), the leading cause of death and disability among
      U.S. adults. Information on the economic impact of CVD associated with inactivity
      is lacking, however, although it is needed to attract more resources for
      preventing CVD and promoting physical activity. PURPOSE: The objective of this
      study was to estimate the direct medical expenditures of CVD associated with
      inactivity. METHODS: A population-based analysis of direct medical expenditure
      was performed by linking the 1996 Medical Expenditure Panel Survey to the 1995
      National Health Interview Survey. The study participants were adults (N = 2,472;
      ages > or = 19 years; not pregnant) in the noninstitutionalized, civilian
      population in 1996. Medical expenditures associated with inactivity were derived
      by comparing the medical expenditures between population groups stratified by
      physical activity and CVD status. RESULTS: In 1996, the prevalence of physical
      inactivity was 47.5%. The overall prevalence of CVD was 21.5% (16.7% in active
      persons, 23.6% in inactive persons, and 49.5% in persons with physical
      limitations). In this population, there were 7.3 million CVD cases. 1.1 million
      of them (15.3%) were associated with inactivity. The total medical expenditure of
      persons with CVD was US 41.3 billion dollars, of which US 5.4 billion dollars
      (13.1%) was associated with inactivity. Applying these percentages to the total
      health and economic burdens of CVD in the United States, there were 9.2 million
      CVD cases (US 23 .7 billion dollars direct medical expenditure) associated with
      inactivity in 2001. CONCLUSIONS: The high economic burden of inactivity
      associated CVD demonstrates the need to promote physical activity among U.S.
      adults.

PMID- 15454356
TI  - Results of Mujeres Felices por ser Saludables: a dietary/breast health randomized
      clinical trial for Latino women.
AB  - BACKGROUND: Data are limited on the efficacy of health-focused interventions for
      young, low-acculturated Latino women. Because breast cancer is the most commonly
      diagnosed cancer and the most common cause of cancer mortality in this
      population, combined interventions that address both early detection and dietary
      patterns could help reduce both morbidity and mortality associated with breast
      cancer in this underserved population. PURPOSE: Mujeres Felices por ser
      Saludables was randomized intervention study designed to assess the efficacy of
      an 8-month combined dietary and breast health intervention to reduce fat and
      increase fiber intake as well as to increase the frequency and proficiency of
      breast self-examination (BSE) and reduce anxiety related to BSE among Latinas.
      METHODS: Blocked randomization in blocks of 6 was used to randomize 256 20- to 40
      year-old Latinas to the intervention (n = 127) or control group (n = 129). The
      intervention group attended an 8-month multicomponent education program designed
      specifically for low-acculturated Latinas. The control group received mailed
      health education material on a schedule comparable to the intervention. A total
      of 195 women (76.2%) completed both the baseline and 8-month follow-up
      interviews. RESULTS: The intervention and control groups were similar on baseline
      sociodemographic characteristics. At the 8-month follow up, the intervention
      group reported lower dietary fat (P < .001) and higher fiber intake (p = .06); a
      higher proportion reported practicing BSE at the recommended interval (p < .001)
      and showed improved BSE proficiency (p < .001) compared to the control group. BSE
      related anxiety was low for both groups at baseline, and no difference in
      reduction was observed. CONCLUSIONS: This project provides a successful model for
      achieving dietary change and improving breast health behavior in young, low
      acculturated Latinas.

PMID- 15454357
TI  - Effects of an oncologist's recommendation to exercise on self-reported exercise
      behavior in newly diagnosed breast cancer survivors: a single-blind, randomized
      controlled trial.
AB  - BACKGROUND: Increased attention has focused on exercise as a quality of life
      intervention for breast cancer survivors during and after adjuvant therapy.
      PURPOSE: Our objective was to examine the effects of an oncologist's
      recommendation to exercise on self-reported exercise behavior in newly diagnosed
      breast cancer survivors attending their first adjuvant therapy consultation.
      METHODS: Using a single-blinded, 3-armed, randomized controlled trial, 450 breast
      cancer survivors were randomly assigned to receive an oncologist exercise
      recommendation only, an oncologist exercise recommendation plus referral to an
      exercise specialist, or usual care. The primary outcome was self-reported total
      exercise (in metabolic equivalent [MET] hours per week) at 5 weeks
      postconsultation. RESULTS: The follow-up assessment rate was 73% (329 of 450).
      Intention-to-treat analysis based on participants with follow-up data indicated a
      significant difference in total exercise in favor of the recommendation-only
      group over the usual care group (mean difference, 3.4 MET hr per week; 95%
      confidence interval [CI], 0.7-6.1 MET hr per week; p = .011). There was no
      significant difference between the recommendation-plus-referral group and the
      usual care group (mean difference, 1.5 MET hr per week; 95% CI, -1.0 to 4.0 MET
      hr per week; p = .244). Ancillary "on-treatment" analyzes showed that
      participants who recalled an exercise recommendation reported significantly more
      total exercise than participants who did not recall an exercise recommendation
      (mean difference, 4.1 MET hr per week: 95% CI, 1.9-6.4 MET hr per week; p <
      .001). CONCLUSIONS: Our findings suggest that an oncologist recommendation may
      increase exercise behavior in newly diagnosed breast cancer survivors,
      particularly if it is recalled 1 week after the recommendation.

PMID- 15454358
TI  - Effects of Hatha yoga and African dance on perceived stress, affect, and salivary
      cortisol.
AB  - BACKGROUND: Dance and yoga have been shown to produce improvements in
      psychological well-being. PURPOSE: The aim of this study was to examine some of
      the psychological and neuroendocrine response to these activities. METHODS: Sixty
      nine healthy college students participated in one of three 90-min classes:
      African dance (n = 21), Hatha yoga (n= 18), or a biology lecture as a control
      session (n = 30). Before and after each condition participants completed the
      Perceived Stress Scale (PSS), completed the Positive Affect and Negative Affect
      Schedule, and provided a saliva sample for cortisol. RESULTS: There were
      significant reductions in PSS and negative affect (ps < .0001) and Time x
      Treatment interactions (ps < .0001) such that African dance and Hatha yoga showed
      significant declines, whereas there was no significant change in biology lecture.
      There was no significant main effect for positive affect (p = .53), however there
      was a significant interaction effect (p < .001) such that positive affect
      increased in African dance, decreased in biology lecture, and did not change
      significantly in Hatha yoga. There was a significant main effect for salivary
      cortisol (p < .05) and a significant interaction effect (p < .0001) such that
      cortisol increased in African dance, decreased in Hatha yoga, and did not change
      in biology. Changes in cortisol were not significantly related to changes in
      psychological variables across treatments. There was 1 significant interaction
      effect (p = .04) such that change in positive affect and change in cortisol were
      negatively correlated in Hatha yoga but positively correlated in Africa dance and
      biology. CONCLUSIONS: Both African dance and Hatha yoga reduced perceived stress
      and negative affect. Cortisol increased in African dance and decreased in Hatha
      yoga. Therefore, even when these interventions produce similar positive
      psychological effects, the effects may be very different on physiological stress
      processes. One factor that may have particular salience is that amount of
      physiological arousal produced by the intervention.

PMID- 15454359
TI  - Factors supporting quality of life over time for individuals with amyotrophic
      lateral sclerosis: the role of positive self-perception and religiosity.
AB  - BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neuromuscular
      disease with no known cure. Maintaining quality of life (QOL) as the disease
      progresses is an important treatment goal. PURPOSE: the purpose of this study is
      to identify factors that support QOL as ALS progresses. METHODS: Changes in QOL
      were monitored in 162 individuals with ALS at 3- to 4-month intervals. Forty-nine
      of the participants survived in the study for over 1 year and were included in a
      longitudinal comparison. The 49 long-term participants were younger and stronger
      at Time 1 than were the participants who died before reaching the 1-year point.
      The McGill Quality of Life Scale demonstrated a high and stable QOL despite
      physical deterioration. RESULTS: Patients maintained a positive self-perception
      of their health despite the physical deterioration. Over time, self-perception of
      health and religiosity were shown to be significantly correlated with QOL.
      CONCLUSIONS: Results support the need for better instrumentation to enable future
      studies to more precisely measure multiple dimensions of ALS-related QOL, to
      identify reference points for self-ratings of both health and QOL, and to capture
      the religious and spiritual mechanisms related to QOL as individuals face the end
      of life.

PMID- 15454360
TI  - Moderating effects of perceived racism on John Henryism and blood pressure
      reactivity in Black female college students.
AB  - BACKGROUND: Relative to other ethnic groups in the United States Blacks have
      disproportionately higher rates of hypertension. Research suggest that perceived
      racism might moderate the relation between such Pearson variables as John
      Henryism and cardiac/vascular functioning. PURPOSE: This study examined the
      possible moderating influence of perceived racism on the John Henryism reactivity
      relation in a sample of 117 Black female college students (M age = 26.10 years,
      SD = 8.83). METHODS: Blood pressure was measured before and during a speaking
      task. John Henryism and perceived racism were assessed via self-report. RESULTS:
      Hierarchial regression analyses revealed that John Henryism was inversely related
      to systolic blood pressure reactivity (p = .007). These analyses also indicated
      that John Henryism and perceived racism interacted to predict both systolic (p =
      .007) and diastolic blood pressure reactivity (p = .0005). Follow-up regression
      analyses indicated that John Henryism was unrelated to systolic and diastolic
      blood pressure reactivity for women high in perceived racism (ps > .62) and was
      inversely associated with systolic and diastolic blood pressure reactivity for
      women low in perceived racism (ps < .01). CONCLUSIONS: The findings highlight the
      importance of examining the potential moderating effects of ethnically relevant
      situation factors when exploring the relation of John Henryism to blood pressure
      reactivity.

PMID- 15454361
TI  - Mothers' perceptions of benefit following pediatric stem cell transplantation: a
      longitudinal investigation of the roles of optimism, medical risk, and
      sociodemographic resources.
AB  - BACKGROUND: This longitudinal study investigated the course and predictors of
      benefit finding among 144 mothers of children undergoing hematopoietic stem cell
      transplantation (HSCT), a severely stressful and life-threatening medical
      procedure. PURPOSE: Children's medical risk and mothers' dispositional optimism
      and sociodemographic resources were examined as predictors of benefit finding.
      The association between benefit finding and mothers' psychosocial adaptation was
      also investigated. METHODS: Assessments occurred during hospitalization for HSCT
      (Time 1 [T1]) and 6 months later (Time 2 [T2]). RESULTS: Hierarchial multiple
      regression analyses revealed that predictors of benefit finding differed
      systematically across assessments, with optimism and medical risk predicting
      benefit finding at both time points but sociodemographic resources predicting
      only T2 benefit findings. Benefit finding did not predict psychosocial adaptation
      until optimism was considered as a moderator of their relation: T1 benefit
      finding was positively associated with T2 adaptation only for mothers high in
      optimism. CONCLUSION: The need for longitudinal research on posttrauma adaptation
      and the utility of considering the natural history of the trauma are discussed.

PMID- 15454362
TI  - Social constraints and distress among women at familial risk for breast cancer.
AB  - BACKGROUND: Despite literature finding support for the social cognitive
      processing model, which suggests that social constraints are related to distress,
      few studies have examined possible mediators of this effect; none have examined
      this relation among women with family histories of breast cancer (FH+). PURPOSE:
      This study was designed to examine possible effects of social constraints on
      psychological distress among FH+ women. METHODS: Six FH+ women (M age = 39.2
      years) completed self-report measures of social constraints, avoidance, and
      general and cancer-specific distress. RESULTS: Multiple regression analyses
      revealed that social constraints were significantly related to both cancer
      specific and general distress and that avoidance partially mediated the relation
      between social constraints and both types of distress. CONCLUSIONS: Theoretical
      and clinical implications of these findings are discussed.

PMID- 15454363
TI  - [Parasitological resistance of Plasmodium falciparum to antimalarial drugs: what
      physicians should keep in mind].
AB  - Plasmodium falciparum drug resistance has considerably modified the attitude of
      physicians in terms of malaria case management. However, a bad understanding of
      the resistance phenomenon can lead to non-appropriate therapeutic and/or public
      health practices. The objective of this paper was to contribute to clarify the
      concept of parasitological resistance by analysing the different types of
      resistance observed in vivo. We showed through some examples that the precision
      of in vivo parasitological results depends on the type of microscopical technique
      used. We also showed that the classification system into resistance levels RI,
      RII, and RIII does not correspond to an increase in the resistance of the
      parasite itself but rather to an increase in the proportion of the resistant
      strains compared to the sensitive ones circulating in a given population. Mutant
      strains are circulating in low proportions as long as there is no selective drug
      pressure. They can be first detected in vitro and, later on, when their
      proportion increase, they are detected in vivo, first in non-immune subjects and
      later in semi-immune subjects. Therefore, the role of the host immunity is
      important in malaria drug resistance. To conclude, increasing use of antimalarial
      drugs (especially in monotherapy) cannot thwart the resistance, but rather leads
      to the selection of mutants strains. As the proportion of the mutant strains
      increases compared to the sensitive (wild) ones, it will reach the microscopic
      detection level and then, the clinical level. It is important that physicians
      involved in malaria case management understand these notions in order to avoid
      non-appropriate therapeutic decisions.

PMID- 15454364
TI  - [Antimalaria drug delivery in pharmacies in non-severe malaria treatment. A
      survey on the quality of the treatment: the case of Bouake (Cote d'Ivoire)].
AB  - In order to assess the action scheme of the National Program against Malaria, a
      study has been conducted in 25 pharmacies in Bouake an area of high malaria
      transmission. The kind and quality of malaria treatments suggested by medical
      personnel, pharmacy sellers and used in automedication have been studied. The
      results proved that chloroquine is the molecule most delivered (25.7%) in private
      pharmacies. The parasitological diagnosis is scarcely requested by medical
      personnel. As in automedication, posological mistakes are relatively frequent
      with medical and pharmacy personnel (29.3%). The duration of the treatment is not
      specified in 14.2% of cases. Training and information actions must be reinforced
      for a better care of malaria.

PMID- 15454365
TI  - [Spinal tuberculosis. Epidemiologic and diagnostic aspects: a study of 28
      clinical observations].
AB  - OBJECTIVE: To rapidly diagnose spinal tuberculosis in order to improve its
      prognosis. METHODS: A retrospective study of 28 clinical observations of patients
      treated in the neurosurgery department of Yopougon's University Teaching Hospital
      during a 7-year period (January 1994-December 2000). The diagnosis of spinal
      tuberculosis was established based on clinical, radiological microbiological and
      histologic arguments. RESULTS: The mean age of the patients is 40 years (from 5
      to 75 years of age). The typical spondylodiscitis was the commonest form observed
      (22 cases) with paravertebral abcess (4 cases). Retropharyngeal abcess was noted
      in two cases. One case of spondylitis was observed. In two cases, there were a
      spondylodiscal lesion associated with neural arch lesion. CT scan was helpful in
      determining the extent of the lesions whereas standard radiography was normal.
      CONCLUSION: The diagnosis is difficult because of the atypical form of spinal
      tuberculosis. These forms need differential diagnosis with spine tumors.

PMID- 15454366
TI  - [Epidemiology of pain in Gabon].
AB  - The authors report on a prospective survey which took place from January 1999 to
      December 2000 - the epidemiology of pain in Gabon - to determine its distribution
      in the population. Ninety-eight women and eighty-four men aged 17 to 80 years old
      (mean age: 50) who consulted at the pain clinic were included in the study, a
      majority of the patients being aged between 21 and 60 years. Lower back pains and
      gonalgias secondary to osteo-arthritis or arthritis were more common in the North
      of the country, where the patients represented 57.7% of the sample, these two
      previous localisations along with cephalagias accounting for 52.7% of the motives
      for the visits. Thoracic and abdominal pains common in both men and women in the
      South were psychological. Patients working in the tertiary sector represented
      45.3% of the patients, those of the secondary sector 24.4%, and those of the
      primary 20.3%. The non-steroidal anti-inflammatory analgesics (NSAI) associated
      with WHO grade 1 and 2 analgesics were effective in 50% of cases, some of whom
      also needed steroidal articular infiltration. Psychological pains were soothed by
      amitriptyline. A specific training of doctors and paramedics in pain treatment is
      necessary to improve care and assistance in this area.

PMID- 15454367
TI  - [Emergency obstetrical hysterectomy: about 58 cases at Libreville Hospital
      Centre].
AB  - OBJECTIVE: To evaluate the incidence, indications and prognosis of this surgery
      in our daily practice in order to suggest preventive action. PATIENTS AND METHOD:
      This is a retrospective study over a period of 10 years, from January 1, 1992 to
      December 31, 2001. Using patient's documents, parameters have been analysed as
      followed: age, parity, antecedent of uterine surgery, indications, surgery
      technique, foeto-maternal prognosis. RESULTS: The frequency of this intervention
      is 0.07%. The average age of patients was 31 years and the average parity was 6.
      The indications were: 44 cases of haemorrage (76%) and 14 cases of post-abortum
      infection (24%). Sub-total hysterectomy was performed on all the patients. We
      have observed 14 cases of maternal death (24%) and 24 cases of foetal death
      (57%). CONCLUSION: The frequency of this surgery is weak in our daily practice,
      compared with other Black African countries. But foeto-maternal prognosis is
      severe. A better sensibilisation of the population on prenatal consultations
      benefits and the setting up of a real national strategy of obstetrical emergency
      care constitute a means to prevent this type of surgery.

PMID- 15454368
TI  - [The prepayment scheme in Rwanda (I): analysis of a pilot experiment].
AB  - Rwanda has made the setting up of a prepayment scheme a priority in its health
      sector reform in order to make health services more financially accessible to the
      population. A pilot study was carried out in three districts. The yearly family
      subscription charge was fixed at 7.9 US dollars, which covers care delivered at
      Health Centre level as well as some services at the hospital. The beneficiaries
      and providers mention difficulties in order to mobilise the subscription charges
      all at a time, the insufficiency of the offer of services at the hospital and the
      absence of involvement of the political authorities in the process. The Ministry
      of Health did initiate the experiment but the choice of the privileged pilot
      districts prevents results from being extrapolated to the country taken as a
      whole with a view to a possible extension at a later stage. Given the relatively
      short time in which it has taken place, the population could neither understand
      the contingency and solidarity issues implied nor have the opportunity to feel
      personally involved in the system. As a conclusion, the study advocates the
      continuation of the experiment with a reinforcement of the coordination which
      should take the weak points identified into account.

PMID- 15454369
TI  - [The prepayment scheme in Rwanda (II): membership and use of services by
      beneficiaries].
AB  - In Rwanda, the Ministry of Health is rebuilding the health sector destroyed
      during the genocide while trying to guarantee the financial accessibility of the
      population to the services through the setting up of a prepayment scheme.
      Membership remains low in the three pilot districts where the prepayment scheme
      was introduced four years before (15,6%). In two of these districts, the curative
      consultation and maternity utilisation has increased appreciably. The members of
      the prepayment scheme make greater use of the services than the rest of the
      population. There is a significantly higher prepayment scheme membership among
      households with a relatively high income and those with a large family (more than
      5 family members). Overall, non-members of the prepayment scheme spend more on
      health services than members do. There are indications that developing the
      prepayment scheme would be very useful for the people in Rwanda if specific
      strategies geared to the poor were set up.

PMID- 15454370
TI  - [Hospitalization charges for patients in the Neurology Department of Lome
      Teaching Hospital].
AB  - For many years the cost of health care in sub-Saharan Africa was largely covered
      by the State. But in September 1987, in view of the economical problems those
      countries had to face, the WHO regional committee adopted the "Bainako's
      Initiative" resolution. This meant that from then on everybody was to pay for
      their health expenses. The purpose of this prospective study which was conducted
      from March 1, 1996 to February 28, 1999 among 316 patients was to assess
      hospitalization charges incurred for patients in the Neurology Department of Lome
      Teaching Hospital with a view to improve the quality of the services provided and
      the accessibility of care. A questionnaire was used and every expense relating to
      the hospitalization of each patient was recorded on a daily basis. The average
      cost is 389,586 (48,485 FCFA for an average stay of 19.7 (2.5 days. This average
      cost is 19 times the minimal monthly salary of a state employee. It can be broken
      down as follows: Accommodation costs represent 52%, medical acts and tests 20.3%
      while drug costs amount to 21.2% and accompanist expenses represent 6.5%. The
      average cost of HIV-infected patients is 635,017 (190,624 FCFA for an average
      stay of 57 (12.9 days. The average cost of HIV-negative patients is 257,354
      (12,837 FCFA for an average stay of 24.4 (1.8 days. To improve the quality of the
      services and the accessibility of care, it is necessary to prescribe and make
      drugs available in their generic form. After a few days in hospital, some
      disabling diseases as strokes, myelopathy and myopathy should be treated at home
      to reduce the length of stay in hospital or in cheaper places such as prolonged
      accommodation centres.

PMID- 15454371
TI  - [Blood transfusion safety in a limited resources setting: the elaboration of a
      rational National Blood Policy in Togo].
AB  - The demand for blood transfusion is high in subSaharan Africa because of the high
      prevalence of the anemia especially due to malaria and obstetrical damage.
      Providing a safe and confident system of transfusion requires more and more
      resources when, in developing countries, these are in fact limited. With a double
      view to improve the coverage in blood transfusion and ensure the security of
      blood products, the Ministry of Health of Togo launched in 1999 a series of
      operations for setting up a rational National Blood Transfusion Policy. The
      following steps were undertaken. A two-week situation analysis of the blood
      transfusion sector highlighted the lack of sector regulation, the multiplicity of
      blood unit production centres (n = 33 for a country of 56,000 km(2)) that could
      endanger the security of the products especially in limited resources conditions,
      the inadequacy in quality management in all areas of blood transfusion
      (insufficiency of human resources, equipment and supply, lack of procedures,
      etc.) and the lack of an information system on blood transfusion for
      retrospective survey and planning. The draft of the National Blood Transfusion
      Policy was then written in a week by two national consultants in accordance with
      the findings of the situation analysis. It was validated during a three-day
      multidisciplinary workshop and an ultimate validation was made by an
      international consultant in order to assess the adequacy of the options
      considered to the country's specific setting. The options retained for developing
      the Togolese blood transfusion sector development and which are consigned in the
      National Blood Transfusion Policy are as follows: development and implementation
      of blood transfusion regulations; reorganisation of the National Transfusion
      System by reducing it to 3 blood unit production centres: one in Lome (the
      capital town), one in the centre of the country (Sokode, 480 km from Lome), and
      one in the Northern part (Dapaong, 870 km from Lome); setting up of a system of
      blood collection, storage and distribution around these centres; promotion of
      voluntary and anonymous blood donation; promotion of quality assurance in the
      system and of good blood prescription practice; development and implementation of
      an appropriate and simple information system for better management;
      identification of a sustainable and equitable financing system in which the State
      must play a key role. The implementation of the National Blood Policy; and in
      particular the achievement of its goals requires: i) permanent State commitment;
      ii) the building of a rational action plan - with a financing framework for all
      blood transfusion partners; and iii) regular program evaluation.

PMID- 15454372
TI  - [An immunisation coverage survey in the Kouilou area of Congo-Brazzaville].
AB  - An internal review of the expanded program of immunisation undertaken on the
      basis of daily data collected over the past five years from 1993 to 1997 in the
      region of Kouilou revealed a weak coverage level for all the antigens, associated
      with a strong dropout rate. In August 1999, a vaccination coverage survey was
      carried out on three strata of the Kouilou area in order to determine the
      proportion of children vaccinated by antigens. The method used is that of
      sampling clusters. It concerned 663 children aged between 12 and 23 months chosen
      among 30 urban, 30 periurban and 30 rural clusters. The BCG scar was found in
      82.8% children while 71.8% had received the third dose of VIP-OPV. Some 62.6%
      were immunised against measles. Within the region, the coverage rates varied from
      87.9 to 57.1% for BCG; 80.3 to 41% for DTP-OPV3 and 7.3 to 41% for measles. A
      considerable variation of dropout rates was observed at area level: 8.9 to 14.7%
      for DTP-OPV3 and 9 to 11% for measles immunisation. The average interval observed
      between VPT-OVP 1 and VPT-OVP 2 was, respectively, 6.1 and 6.2 weeks in urban
      areas against 6.4 and 6.9 weeks in periurban areas. On the other hand in rural
      zones, the interval was of 7.6 weeks between VPT-OVP and DPT-OPV2 and of 10.1
      weeks between DPT-OVP2 and DPT-OVP3. The median interval was of 5 weeks for the
      different DPT-OVP doses in all the strata. The vaccination card was found in 90%
      of cases in urban areas, 96% in urban zones and 55% in rural zones. The coverage
      level attained per antigen is satisfactory, but remains to be strengthened.
      Dropout rates are high enough and they should be corrected. Follow-up actions
      should focus on raising a strong awareness for vaccination in rural areas.
      Besides, the vaccination of target populations living in remote areas by way of
      mobile and outreach strategies could improve the immunisation coverage rate.

PMID- 15454373
TI  - Repair of mycotic coronary aneurysm without cardiopulmonary bypass: case report.
AB  - Mycotic aneurysms of the coronary arteries are extremely rare, with 15 cases
      reported. We report the successful treatment of a mycotic aneurysm of the left
      anterior descending coronary artery by coronary artery bypass grafting with
      aneurysm ligation and resection without the use of cardiopulmonary bypass.

PMID- 15454374
TI  - A long-term porcine model for evaluation of prosthetic heart valves.
AB  - BACKGROUND: Animal experimental testing is imperative for preclinical evaluation
      of prosthetic heart valves and implantation techniques. Because human and pig
      cardiovascular structures including mitral valves show remarkable anatomical
      similarity, these animals are good candidates for preclinical testing. Previous
      attempts to establish such long-term models were hampered by both intra- and
      postoperative difficulties. Our aim was to overcome these difficulties to develop
      a porcine model for mitral valve replacement (MVR) and furthermore to investigate
      the practical feasibility of 3 chordal reconstruction procedures. METHODS:
      Sixteen 60-kg pigs were allocated to undergo 1 of 3 surgical procedures, (1)
      preservation of the entire subvalvular apparatus (n = 8), (2) preservation of the
      secondary chordae only (n = 4), or (3) excision of the native valve and papillary
      resuspension with sutures (n = 4). St. Jude Medical valves (29 mm) were implanted
      during extracorporeal circulation and cold cardioplegic arrest. Postoperative
      anticoagulation was administered by subcutaneous heparin injections. RESULTS:
      Fourteen animals survived 1 month, thriving and without signs of heart failure.
      One animal was euthanized due to irreversible bleeding in the tracheal tube, and
      another animal died on the third postoperative day owing to valve thrombosis.
      CONCLUSION: A practically feasible long-term porcine model of MVR has been
      established. Because the pig is superior to other species with respect to
      anatomical and physiological similarity to humans, we consider this model as an
      optimal platform for experimental preclinical testing of heart valve prostheses.

PMID- 15454375
TI  - Magnetic resonance imaging to detect acute cerebral events in on-pump and hybrid
      pump patients.
AB  - BACKGROUND: Conventional cardiopulmonary bypass results in cerebral ischemic
      sequelae that may be reduced with hybrid pump technologies, such as the
      CardioVention system (CardioVention, Santa Clara, CA, USA). CardioVention differs
      from conventional bypass in that it has a novel air elimination module and
      reduced membrane surface area and priming volume. This preliminary study tested
      whether this pump confers neurological safety advantages over conventional
      bypass. METHODS: Ten patients were studied, with 6 assigned to on-pump coronary
      artery bypass grafting and 4 to the CardioVention system. No patients had any
      stroke history. Within 72 hours postsurgery, each underwent diffusion-weighted
      magnetic resonance imaging, a sensitive test for cerebral ischemic events.
      RESULTS: Two on-pump patients (33%) had postoperative findings on imaging, but
      none of the CardioVention patients demonstrated comparable changes ( P =.47). No
      patients had symptoms of acute stroke. CONCLUSION: Postoperative magnetic
      resonance imaging showed a trend toward a greater rate of ischemic events in
      patients undergoing traditional on-pump surgery. These preliminary findings
      suggest that hybrid pump technologies, such as the CardioVention system, may
      attenuate the risk of short-term neurological complications. Future studies are
      indicated to confirm these subclinical ischemic changes and to correlate them
      with long-term neurocognitive changes.

PMID- 15454376
TI  - Giant left atrial myxoma in a patient with mitral insufficiency: case report.
AB  - We describe a 57-year-old female patient with left atrial giant myxoma and
      peroperative defined mitral insufficiency who underwent surgery with a diagnosis
      of a left atrial myxoma without accompanying mitral insufficiency. Although no
      clinical findings of mitral insufficiency were noticed preoperatively, after
      myxoma resection moderate mitral insufficiency was observed during surgery.
      Mitral insufficiency was repaired with annuloplasty. The patient recovered
      without complication.

PMID- 15454377
TI  - Intraoperative and postoperative variables associated with strokes following
      cardiac surgery.
AB  - BACKGROUND: Strokes are a devastating complication of coronary artery bypass
      grafting (CABG) surgery. Previous work from 1992 to 2000 determined the principal
      mechanism of strokes occurring secondary to CABG. In the present study, we
      quantified the association between intraoperative and postoperative variables and
      stroke mechanisms while adjusting for patient and disease characteristics.
      METHODS: We conducted a prospective study of 13,897 patients who underwent
      isolated CABG in northern New England from 1992 to 2000. Data were collected on
      patient and disease characteristics, intraoperative and postoperative care, and
      outcomes. Strokes were classified as embolic, hypoperfusion, and mixed
      (hemorrhage, lacunar, thrombotic, other, multiple, and unclassified). We
      quantified the association between the intraoperative and postoperative treatment
      and course variables and the stroke mechanism while adjusting for patient and
      disease characteristics. Patients without strokes served as the reference group
      for the determination of odds ratios (OR). RESULTS: Variables associated with
      embolic strokes included cardiopulmonary bypass time greater than 2 hours versus
      less than 1 hour (OR, 1.5; ptrend.03) and postoperative atrial fibrillation (OR,
      2.4; P <.001). The risk of hypoperfusion strokes was increased with the duration
      of cardiopulmonary bypass (OR, 6.4; ptrend.01) and postoperative atrial
      fibrillation (OR, 5.4; P <.001). Postoperative atrial fibrillation was associated
      with the risk of mixed strokes (OR, 1.7; P =.04). CONCLUSIONS: After we adjusted
      for preoperative factors, postoperative atrial fibrillation and increasing
      duration of cardiopulmonary bypass remained significant predictors of embolic and
      hypoperfusion strokes, although to differing degrees. Prevention and management
      of atrial fibrillation and avoidance of prolonged exposure to extracorporeal
      circulation may offer leverage areas for the improvement of stroke outcomes.

PMID- 15454378
TI  - Skeletonized radial artery grafting: one-year patency rate.
AB  - BACKGROUND: The skeletonized radial artery harvesting technique has routinely
      been used in our institute. Its clinical outcome is acceptable; however, the
      graft patency rate at 1 year has not been reported. METHODS: Between July 1,
      2003, and October 31, 2002, 50 consecutive patients underwent isolated coronary
      artery bypass using skeletonized radial artery grafts in our hospital. There were
      no hospital deaths or perioperative myocardial infarctions. All patients
      completed follow-up by November 2003. Twenty of these patients (18 asymptomatic
      volunteers and 2 symptomatic patients) underwent coronary angiography at 1 year,
      and the results were analyzed. RESULTS: At a mean (+/-SD) follow-up period of 1.2
      +/- 0.2 years, there were no deaths. Two patients developed angina due to graft
      occlusion (1 in the radial artery and another in the gastroepiploic artery).
      Twenty-one radial artery grafts and 36 distal anastomoses with radial artery
      grafts were evaluated by angiography at 1 year (0.9 +/- 0.1 years). There was 1
      radial artery graft occlusion affecting 1 distal anastomosis, giving a perfect
      graft patency rate of 95.2% (20/21) and a perfect anastomosis patency rate of
      97.2% (35/36). The patient with the occluded radial artery graft had a history of
      peripheral vascular disease and diabetes. There were no graft stenoses or string
      signs. CONCLUSION: At our limited follow-up, the results of using skeletonized
      radial artery grafts are excellent. Extensive skeletonization will not affect the
      graft patency rate or early graft spasm. Careful examinations of the radial
      artery grafts in patients with a history of peripheral artery disease and
      diabetes are mandated.

PMID- 15454379
TI  - Intramyocardial CD34+ cell transplantation combined with off-pump coronary artery
      bypass grafting.
AB  - This report describes a new therapeutic approach for severe ischemic heart
      disease, intramyocardial transplantation of autologous bone marrow-derived CD34 +
      cells combined with off-pump coronary artery bypass grafting (CABG). CD34 is
      widely known as a cell surface antigen expressed on hematopoietic stem cells, and
      recent experimental studies have shown that CD34 + cells include endothelial
      progenitor cells. We used the Isolex 300i magnetic cell selection system to
      separate CD34 + cells from bone marrow cells. This report describes the first
      case treated with the combination of off-pump CABG and cell transplantation for
      therapeutic angiogenesis and myocardial regeneration. The transplantation of
      autologous bone marrow-derived CD34 + cells improved perfusion of the ungraftable
      ischemic area.

PMID- 15454381
TI  - Calculated reduction aortoplasty for dilatation of the ascending aorta associated
      with aortic valve replacement.
AB  - BACKGROUND: Previous studies have advocated reduction aortoplasty to normalize
      the diameter of a moderately dilated ascending aorta associated with aortic valve
      disease. One of the reported techniques is the shawl lapel aortoplasty, which we
      have adopted and modified by setting a simple set of calculations. We present our
      midterm results. METHODS: Between February 1996 and February 2004, 25 patients
      underwent reduction aortoplasty during replacement of their aortic valves.
      Concomitant cardiac procedures were performed in 11 patients. Eighteen patients
      had predominantly severe aortic valve stenosis and 7 patients moderate to severe
      aortic valve insufficiency. Ascending aortic aneurysm size ranged from 43 to 50
      mm, measured echocardiographically. In one small sized patient the aorta was 38
      mm. Following their discharge patients were instructed to have control
      echocardiograms every 6 months for the first postoperative year and then
      annually. They were interviewed by telephone annually to date. RESULTS: There
      were no hospital deaths. Twenty-four patients were alive at follow-up, at 2 to 96
      months (average 2.9 years). There was one late death, 2 years postoperatively.
      The first follow-up transthoracic echocardiogram performed at a mean of 6.2
      months postoperatively (range, 1-11 months), as well as the subsequent annual
      echocardiograms in all patients, showed no evidence of further enlargement of the
      ascending aorta, compared to the reduced diameter obtained during the initial
      operation. The first 3 patients of this study remained essentially unchanged
      postoperatively, with only a minor reduction of their aortic diameter.
      CONCLUSIONS: The shawl lapel technique based on simple calculations, used as a
      diameter-reduction strategy for ascending aortic dilatation encountered during
      aortic valve replacement, is an efficacious method with excellent medium-term
      results.

PMID- 15454382
TI  - Candida albicans endocarditis and a review of fungal endocarditis: case report.
AB  - Endocarditis due to fungal etiology is rare, but it is the most severe form of
      infective endocarditis. Fungal endocarditis is commonly complicated by systemic
      embolizations, and the difficulty in isolating the fungi with routine blood
      cultures complicates the diagnostic process. In these culture-negative cases of
      endocarditis, etiologic diagnosis is made with histopathologic examination of the
      cardiac valve, embolic materials, and systemic ulcers. In this case report, the
      presented patient with fungal endocarditis and its neurologic complications was
      treated with a surgical and medical approach.

PMID- 15454383
TI  - Infected aortic pseudoaneurysm at the site of a proximal mechanical anastomosic
      connector following off-pump coronary artery bypass grafting: case report.
AB  - We describe a patient who underwent off-pump coronary artery bypass graft surgery
      performed with an aortic connector. The patient developed a malignant deep
      sternal wound infection that subsequently led to an aortic pseudoaneurysm at the
      site of proximal anastomosis.

PMID- 15454384
TI  - Aneurysm of aortocoronary saphenous vein graft: case report and literature
      review.
AB  - True aneurysms of aortocoronary saphenous vein bypass grafts are a relatively
      rare complication of bypass surgery, but because the complications of thrombosis,
      embolization, or rupture are potentially fatal, this condition requires immediate
      surgical intervention. We describe a 78-year-old man who had undergone coronary
      bypass 15 years previously and who presented with a saphenous vein graft that was
      severely degenerated and aneurysmally enlarged throughout its course, measuring
      as much as 5 to 6 cm in certain locations. Redo coronary artery bypass grafting
      using the right and left internal thoracic arteries and resection of the aneurysm
      were performed. We also present a review of the literature regarding diagnosis,
      management, and treatment of this condition.

PMID- 15454385
TI  - Oral anticoagulation therapy in children: successfully controlled by self
      management.
AB  - BACKGROUND: Children with congenital heart disease and who are on oral
      anticoagulation therapy present special challenges due to, for example, rapid
      fluctuations in international normalized ratio (INR) values, interruption in
      daily life due to frequent hospital/doctor visits, and difficulties and pain to
      the child in the performance of venipuncture. We hypothesize that oral
      anticoagulation therapy can be successfully controlled by self-management for
      this subset of patients. The aim of this study was to assess the treatment
      quality of self-managed oral anticoagulation therapy as the proportion of time
      within the therapeutic INR target range in children with congenital heart
      disease. METHODS: Children (N = 22) with a mean age of 10.6 years (range, 1.8
      18.6 years) and their parents were trained in home blood analysis of INR and in
      coumarin dosage adjustment. After training, the children were monitored by weekly
      INR measurements. The therapeutic range in target INR values was +/-0.5. The
      indications for initiating oral anticoagulation therapy were the presence of a
      mechanical heart valve (n = 16) and total cavopulmonary connection (n = 6). The
      children had no physical restrictions. RESULTS: The mean observation time was 3.6
      years (range, 0.9-5.8 years), and the total number of patient-years was 75.4. The
      patients were within the therapeutic INR target range for a median of 73.1%
      (range, 30.3%-91.0%) of the observation time. Two children died for reasons not
      related to the oral anticoagulation therapy. None of the patients experienced
      thromboembolic or bleeding complications requiring doctor intervention.
      CONCLUSION: Self-management of oral anticoagulation therapy is safe and provides
      a good quality of treatment for selected children with congenital heart disease.

PMID- 15454386
TI  - Editorial: Women and heart disease.

PMID- 15454387
TI  - A new technical approach for sternal closure with suture anchors (Dogan
      technique).
AB  - OBJECTIVES: Various methods for sternal approximation have been described
      previously. Some patients undergoing these procedures are at risk for sternal
      dehiscence and mediastinitis. We used a different method, with a suture anchor
      system, for median sternotomy closure as an alternate technique in patients with
      a high risk of postoperative sternal dehiscence and sternal nonunion. MATERIAL
      AND METHOD: Suture anchor systems have been developed principally for the
      fixation of tendons or ligaments to the bone. We first used the suture anchor
      system for median sternotomy closure, although it has been frequently used in
      various orthopedic surgical procedures. In this report, we describe the use,
      after fresh cadaveric tests, of an alternative technique in a patient undergoing
      coronary artery bypass grafting. RESULTS: There were no complications due to the
      suture anchor device, and successful application was performed for sternotomy
      fixation after surgical procedure in a patient. The standard techniques have
      several disadvantages, such as osteomyelitis, chondritis, cutting into the
      sternum and sternal dehiscence, prolonged hospitalization, and increased
      mortality and morbidity due to the listed complications, but these devices may
      protect the wire from cutting into the sternal bone. CONCLUSION: We propose
      suture anchors for reapproximation of the sternum to decrease the complications
      related to surgical steel wires. We therefore consider this technique to be easy,
      safe, and effective in patients with diabetes mellitus or severe osteoporosis
      considered to have risk for sternal dehiscence postoperatively. Another advantage
      of this suture system is that the titanium wire makes it more magnetic resonance
      compatible than systems using surgical steel wire.

PMID- 15454388
TI  - Experience with various surgical options for the treatment of atrial
      fibrillation.
AB  - BACKGROUND: New alternatives exist using various energy sources and lesion lines
      for the surgical treatment of atrial fibrillation (AF). The efficacy of these
      options compared to the cut-and-sew maze III procedure is unknown. METHODS: From
      August 1996 to August 2003, 79 patients have undergone a procedure for AF, with
      70 patients currently more than 3 months postsurgery. The patients (58
      continuous, 12 paroxysmal) underwent a surgical procedure for AF, lone AF (12)
      and with concomitant procedures (58). Techniques included cut and sew (23),
      bipolar radiofrequency (RF) (28) and unipolar-RF (10), and cryothermy (9).
      Lesions included maze III (46), pulmonary vein isolation (16), and pulmonary vein
      isolation plus mitral annular connecting line only (8). RESULTS: Follow-up was
      complete in 58 (83%) of 70 patients at a mean time of 595 +/- 750 days (range, 24
      2530 days). The operative mortality was 0% in lone AF patients and 7.1% (5/70) in
      patients undergoing concomitant procedures. Need for perioperative pacemaker was
      22.9%. Overall, normal sinus rhythm (NSR) was restored in 82.7% of patients, with
      success in 83.3% (10/12) lone procedures and 82.6% (38/46) concomitant procedures
      ( P = NS); the rate of continuous AF was 85.1% (40/47) and SR with paroxysmal
      fibrillation was 72.7% (8/11) ( P = NS). Traditional maze was successful in 80.6%
      (29/36) patients, pulmonary vein isolation was successful 93.3% (14/15), and left
      sided maze in 71.4% (5/7) ( P = NS). Cut and sew procedures were successful in
      88.2% (15/17), RF-bipolar in 84.0% (21/25), RFunipolar in 77.8% (7/9), and
      cryothermy in 71.4% (5/7) ( P = NS). Energy source, lesion set, AF duration, and
      lone/concomitant procedure were the factors subjected to logistic regression
      analysis. No factors were predictive of achieving postoperative NSR. CONCLUSIONS:
      Our early experience with newer surgical techniques employing different energy
      sources and fewer incision lines suggests that the success rate may approach the
      results obtained with traditional cut-and-sew Cox-maze III procedures.

PMID- 15454389
TI  - Mitral valve operations through standard and smaller incisions.
AB  - OBJECTIVE: Evaluate the operative results of mitral valve repair (MVV) and mitral
      valve replacement (MVR) performed through standard and smaller incisions.
      METHODS: From January 1997 through December 2002, 821 consecutive patients
      underwent mitral valve operation. Of these procedures, 475 were MVV and 346 were
      MVR. A logistic regression model was developed to identify the risk factors for
      early mortality and to evaluate the effect of replacement versus repair and
      standard versus small incision. RESULTS: Replacement patients were older, more
      likely New York Heart Association (NYHA) class III or IV, more likely female, and
      had more frequent previous median sternotomy and stroke (all P <.05). The mitral
      diagnoses in the 2 groups were markedly different. Prolapse and ischemia
      dominated the repairs, whereas calcific and rheumatic diagnoses required
      replacement. There were 667 concomitant procedures performed on these patients,
      most commonly coronary artery bypass graft (229), aortic valve replacement (170),
      maze (79), and tricuspid valve (TV) repair/replacement (73). Thirty-three
      patients (4.0%) died in the postoperative period, 2.3% after repair and 6.4%
      after replacement ( P <.01). Endocarditis (4/17), calcific disease (7/73), and
      ischemic disease (9/121) accounted for 26% of patients and 60% of deaths.
      Multivariate regression analysis identified NYHA class, emergent status,
      concomitant TV operation, and history of renal failure, but not repair versus
      replacement, as independent risk factors predicting mortality. We estimated that
      356 of the 821 patients (43%) were candidates for small-incision operations, the
      others were excluded by the need for concomitant procedure or other cause. A
      total of 205/356 (57%) actually underwent small-incision operations, all with
      central cannulation and standard techniques. From 1997-1999, 32% of eligible
      patients were so treated, but from 2000-2002, with increasing surgeon experience,
      this percentage rose significantly to 71% ( P <.01). Eligible patients who
      underwent small-incision operation were younger and had lower NYHA
      classifications, lower preoperative creatinine, and shorter length of stay (all P
      <.01) than those who had standard incisions. Cross-clamp time, perfusion time,
      and mortality rate were not significantly different. CONCLUSIONS: The mortality
      rate for MV operations is concentrated among a few diagnoses. In some patients
      surgery may be approached safely through smaller incisions without introducing
      new elements of operative risk.

PMID- 15454390
TI  - Human organic anion transporter MRP4 (ABCC4) is an efflux pump for the purine end
      metabolite urate with multiple allosteric substrate binding sites.
AB  - The end product of human purine metabolism is urate, which is produced primarily
      in the liver and excreted by the kidney through a well-defined basolateral blood
      to-cell uptake step. However, the apical cell-to-urine efflux mechanism is as yet
      unidentified. Here, we show that the renal apical organic anion efflux
      transporter human multidrug resistance protein 4 (MRP4), but not apical MRP2,
      mediates ATP-dependent urate transport via a positive cooperative mechanism (K(m)
      of 1.5 +/- 0.3 mM, V(max) of 47 +/- 7 pmol x mg(-1) x min(-1), and Hill
      coefficient of 1.7 +/- 0.2). In HEK293 cells overexpressing MRP4, intracellular
      urate levels were lower than in control cells. Urate inhibited methotrexate
      transport (IC50 of 235 +/- 8 microM) by MRP4, did not affect cAMP transport,
      whereas cGMP transport was stimulated. Urate shifted cGMP transport by MRP4 from
      positive cooperativity (K(m) and V(max) value of 180 +/- 20 microM and 58 +/- 4
      pmol x mg(-1) x min(-1), respectively, Hill coefficient of 1.4 +/- 0.1) to single
      binding site kinetics (K(m) and V(max) value of 2.2 +/- 0.9 mM and 280 +/- 50
      pmol x mg(-1) x min(-1), respectively). Finally, MRP4 could transport urate
      simultaneously with cAMP or cGMP. We conclude that human MRP4 is a unidirectional
      efflux pump for urate with multiple allosteric substrate binding sites. We
      propose MRP4 as a candidate transporter for urinary urate excretion and suggest
      that MRP4 may also mediate hepatic export of urate into the circulation, because
      of its basolateral expression in the liver.

PMID- 15454391
TI  - Omi/HtrA2 protease mediates cisplatin-induced cell death in renal cells.
AB  - Omi/HtrA2 is a mitochondrial proapoptotic serine protease that is able to induce
      both caspase-dependent and caspase-independent cell death. After apoptotic
      stimuli, Omi is released to the cytoplasm where it binds and cleaves inhibitor of
      apoptosis proteins. In this report, we investigated the role of Omi in renal cell
      death following cisplatin treatment. Using primary mouse proximal tubule cells,
      as well as established renal cell lines, we show that the level of Omi protein is
      upregulated after treatment with cisplatin. This upregulation is followed by the
      release of Omi from mitochondria to the cytoplasm and degradation of XIAP.
      Reducing the endogenous level of Omi protein using RNA interference renders renal
      cells resistant to cisplatin-induced cell death. Furthermore, we show that the
      proteolytic activity of Omi is necessary and essential for cisplatin-induced cell
      death in this system. When renal cells are treated with Omi's specific inhibitor,
      ucf-101, they become significantly resistant to cisplatin-induced cell death. Ucf
      101 was also able to minimize cisplatin-induced nephrotoxic injury in animals.
      Our results demonstrate that Omi is a major mediator of cisplatin-induced cell
      death in renal cells and suggest a way to limit renal injury by specifically
      inhibiting its proteolytic activity.

PMID- 15454392
TI  - 17beta-Estradiol replacement improves renal function and pathology associated
      with diabetic nephropathy.
AB  - The protective factor of female gender appears to be lost in diabetes; the
      incidence of diabetes and its complications, including diabetic nephropathy, are
      equal in women and men. This study examined the effects of estrogen deficiency by
      ovariectomy (OVX) and replacement with 17beta-estradiol (OVX+E2) on renal
      function and pathology in the nondiabetic (ND) and streptozotocin (STZ)-induced
      diabetic (D) rat kidneys for 12 wk. Diabetes was associated with an increase in
      urine albumin excretion (UAE; ND, 0.39 +/- 0.03; D, 5.9 +/- 0.8 mg/day; P <
      0.001), decrease in creatinine clearance (CrCl; ND, 0.69 +/- 0.03; D, 0.43 +/-
      0.09 mg x min(-1) x 100 g body wt(-1); P < 0.05), increase in the index of
      glomerulosclerosis [GSI; ND, 0.01 +/- 0.01; D, 0.15 +/- 0.04 arbitrary units
      (AU); P < 0.01], tubulointerstitial fibrosis (TIFI; ND, 0.04 +/- 0.04; D, 0.68 +/
      0.2 AU; P < 0.01), and transforming growth factor-beta (TGF-beta) protein
      expression (ND, 0.61 +/- 0.02; D, 1.25 +/- 0.07 AU; P < 0.01). In the D group,
      the severity of these changes was augmented with OVX (UAE, 8.1 +/- 0.6 mg/day;
      CrCl, 0.40 +/- 0.04 mg x min(-1) x 100 g body wt(-1); GSI, 0.29 +/- 0.04 AU;
      TIFI, 0.90 +/- 0.06 AU; TGF-beta, 1.26 +/- 0.10 AU), whereas E2 replacement
      attenuated these changes (UAE, 6.3 +/- 0.8 mg/day; CrCl, 0.66 +/- 0.03 mg x min(
      1) x 100 g body wt(-1); GSI, 0.06 +/- 0.02 AU; TIFI, 0.36 +/- 0.08 AU; TGF-beta,
      0.57 +/- 0.08 AU). We conclude that E2 deficiency increases the severity of renal
      disease in a diabetic animal model and that E2 replacement is renoprotective by
      attenuating the decline in renal function and pathology associated with diabetes.

PMID- 15454394
TI  - Receptor tyrosine kinases mediate epithelial Na(+) channel inhibition by
      epidermal growth factor.
AB  - Epidermal growth factor (EGF) decreases Na(+) reabsorption across distal nephron
      epithelia. Activity of the epithelial Na(+) channel (ENaC) is limiting for Na(+)
      transport in this portion of the nephron. Abnormal ENaC activity and EGF
      signaling are both associated with polycystic kidney disease localized to the
      distal nephron. We tested here whether EGF and other ligands for receptor
      tyrosine kinases (RTK) decrease ENaC activity. EGF markedly and quickly decreased
      ENaC activity. The RTK inhibitor erbstatin blocked EGF actions on ENaC and when
      added alone increased channel activity, uncovering basal suppression by
      endogenous RTK. The protein tyrosine phosphatase inhibitor vanadate, similar to
      EGF, decreased ENaC activity. Growth factors and vanadate decreased ENaC activity
      by decreasing open probability. ENaC was not phosphorylated in response to EGF,
      indicating that intermediary proteins transduce the inhibitory signal from the
      EGF receptor (EGFR) to ENaC. We find that neither MAPK 1/2 nor c-Src is signaling
      intermediaries between EGFR and ENaC. Inhibition of ENaC paralleled decreases in
      plasma membrane phosphatidylinositol 4,5-bisphosphate levels [PtdIns(4,5)P(2)]
      and was abolished by clamping PtdIns(4,5)P(2). We conclude that EGF and other
      ligands for RTK decrease ENaC open probability by decreasing membrane
      PtdIns(4,5)P(2) levels.

PMID- 15454393
TI  - Phosphatonin washout in Hyp mice proximal tubules: evidence for
      posttranscriptional regulation.
AB  - X-linked hypophosphatemia is the most common inherited form of rickets. It is
      characterized by renal phosphate wasting, leading to hypophosphatemia and an
      inappropriately normal or low serum level of 1,25(OH)2 vitamin D. Previous
      studies have pointed to a circulating factor or phosphatonin-inhibiting phosphate
      transport by decreasing mRNA of the proximal tubule NaP(i) cotransporter NaPi-2A.
      The present study examined the hypothesis that there was also posttranscriptional
      regulation of the NaPi-2A cotransporter in Hyp mice proximal tubules and whether
      the phosphate transport defect in Hyp mice persisted when they were studied in
      vitro. We found that the rate of phosphate transport in Hyp mice was <50% that in
      C57/B6 control mice. While phosphate transport remained stable during incubation
      with time in C57/B6 mice proximal tubules, it increased from 0.46 +/- 0.47 to
      1.83 +/- 0.40 pmol x mm(-1) x min(-1) in Hyp proximal tubules (P < 0.01)
      consistent with phosphatonin washout in Hyp proximal tubules perfused in vitro.
      This time-dependent increase in phosphate transport was still observed in the
      presence of cycloheximide. There was also a reduction of proximal tubule apical
      NaPi-2A expression from Hyp mice compared with C57/B6 mice using single-tubule
      immunohistochemistry. Using immunohistochemistry, we demonstrate an increase in
      apical expression of the NaPi-2A transporter in proximal tubules perfused in
      vitro in Hyp mice even in the presence of bath cycloheximide. The increase in
      apical expression of the NaPi-2A transporter in proximal tubules perfused in
      vitro in Hyp mice was blocked by colchicine. These data are consistent with a
      rapidly reversible posttranscriptional defect in Hyp mice causing a reduction in
      phosphate transport.

PMID- 15454395
TI  - Inhibition of ROMK potassium channel by syntaxin 1A.
AB  - ROMK potassium channels are present in the cortical collecting duct (CCD) of the
      kidney and serve as apical exit pathways for K+ secretion in this nephron
      segment. K+ secretion in the CCD is regulated by multiple factors. In this study,
      we show that syntaxin 1A, but not syntaxin 3 or 4, inhibited whole cell ROMK
      currents in Xenopus laevis oocytes. Syntaxin 1A, but not syntaxin 3 or 4,
      interacted with the COOH-terminal cytoplasmic domain of ROMK in intro.
      Coexpression with synaptobrevin 2 reversed inhibition of whole cell ROMK currents
      by syntaxin 1A. In excised inside-out membranes of oocytes, application of fusion
      proteins containing the cytoplasmic region of syntaxin 1A to the cytoplasmic face
      caused a dose-dependent inhibition of ROMK. We further examined regulation of the
      K+ channels in the CCD by syntaxin 1A. Application of botulinum toxin C1 to the
      excised inside-out membranes of the CCD caused an increase in the activity of K+
      channels. In contrast, application of toxin B had no effects. These results
      suggest that syntaxin 1A causes a tonic inhibition of the K+ channels in the
      apical membrane of the CCD. Binding of synaptobrevin 2 to syntaxin 1A during
      docking and fusion of transport vesicles to the plasma membranes of CCD may lead
      to activation of these channels.

PMID- 15454396
TI  - Weight loss through ileal transposition is accompanied by increased ileal hormone
      secretion and synthesis in rats.
AB  - Bariatric surgeries, such as gastric bypass, result in dramatic and sustained
      weight loss that is usually attributed to a combination of gastric volume
      restriction and intestinal malabsorption. However, studies parceling out the
      contribution of enhanced intestinal stimulation in the absence of these two
      mechanisms have received little attention. Previous studies have demonstrated
      that patients who received intestinal bypass or Roux-en-Y surgery have increased
      release of gastrointestinal hormones. One possible mechanism for this increase is
      the rapid transit of nutrients into the intestine after eating. To determine
      whether there is increased secretion of anorectic peptides produced in the distal
      small intestine when this portion of the gut is given greater exposure to
      nutrients, we preformed ileal transpositions (IT) in rats. In this procedure, an
      isolated segment of ileum is transposed to the jejunum, resulting in an
      intestinal tract of normal length but an alteration in the normal distribution of
      endocrine cells along the gut. Rats with IT lost more weight (P < 0.05) and
      consumed less food (P < 0.05) than control rats with intestinal transections and
      reanastomosis without transposition. Weight loss in the IT rats was not due to
      malabsorption of nutrients. However, transposition of distal gut to a proximal
      location caused increased synthesis and release of the anorectic ileal hormones
      glucagon-like peptide-1 (GLP-1) and peptide YY (PYY; P < 0.01). The association
      of weight loss with increased release of GLP-1 and PYY suggests that procedures
      that promote gastrointestinal endocrine function can reduce energy intake. These
      findings support the importance of evaluating the contribution of
      gastrointestinal hormones to the weight loss seen with bariatric surgery.

PMID- 15454397
TI  - Comparison of cellular and medium insulin and GABA content as markers for living
      beta-cells.
AB  - Experimental and therapeutic use of islet cell preparations could benefit from
      assays that measure variations in the mass of living beta-cells. Because
      processes of cell death can be followed by depletion and/or discharge of cell
      specific substances, we examined whether in vitro conditions of beta-cell death
      resulted in changes in tissue and medium content of insulin and of gamma
      aminobutyric acid (GABA), two beta-cell-specific compounds with different
      cellular localization and turnover. Exposure of rat purified beta-cells to
      streptozotocin (5 mM, 120 min) or to the nitric oxide donor GEA-3162 (GEA; 50
      microM, 120 min) caused 80% necrosis within 24 h; at the end of this period,
      cellular insulin content was not significantly decreased, but cellular GABA
      content was reduced by 70%; when cultured at basal glucose (6 mM), the toxin
      exposed cells did not discharge less insulin but released 80% less GABA in the
      period 8-24 h. As in rat beta-cell purification, GABA comigrated with insulin
      during human islet cell isolation. Twenty-four hours after GEA (500 microM, 120
      min), human islet cell preparations exhibited 90% dead cells and a 45 and 90%
      reduction, respectively, in tissue insulin and GABA content; in the period 9-24
      h, insulin discharge in the medium was not reduced, but GABA release was
      decreased by 90%. When rat beta-cells were cultured for 24 h with nontoxic
      interleukin (IL)-1beta concentrations that suppressed glucose-induced insulin
      release, cellular GABA content was not decreased and GABA release increased by
      90% in the period 8-24 h. These data indicate that a reduction in cellular and
      medium GABA levels is more sensitive than insulin as a marker for the presence of
      dead beta-cells in isolated preparations. Pancreatic GABA content also rapidly
      decreased after streptozotocin injection and remained unaffected by 12 h of
      hyperglycemia. At further variance with insulin, GABA release from living beta
      cells depends little on its cellular content but increases with IL-1beta-induced
      alterations in beta-cell phenotype.

PMID- 15454398
TI  - Differential expression of Kv4 pore-forming and KChIP auxiliary subunits in rat
      uterus during pregnancy.
AB  - Regulation of voltage-gated K(+) (K(v)) channel expression may be involved in
      controlling contractility of uterine smooth muscle cells during pregnancy.
      Functional expression of these channels is not only controlled by the levels of
      pore-forming subunits, but requires their association with auxiliary subunits.
      Specifically, rapidly inactivating K(v) current is prominent in myometrial cells
      and may be carried by complexes consisting of Kv4 pore-forming and KChIP
      auxiliary subunits. To determine the molecular identity of the channel complexes
      and their changes during pregnancy, we examined the expression and localization
      of these subunits in rat uterus. RT-PCR analysis revealed that rat uterus
      expressed all three Kv4 pore-forming subunits and KChIP2 and -4 auxiliary
      subunits. The expression of mRNAs for these subunits was dynamically and region
      selectively regulated during pregnancy. In the corpus, Kv4.2 mRNA level increased
      before parturition, whereas the expression of Kv4.1 and Kv4.3 mRNAs decreased
      during pregnancy. A marked increase in KChIP2 mRNA level was also seen at late
      gestation. In the cervix, the expression of all three pore-forming and two
      auxiliary subunit mRNAs increased at late gestation. Immunoprecipitation followed
      by immunoblot analysis indicated that Kv4.2-KChIP2 complexes were significant in
      uterus at late pregnancy. Kv4.2- and KChIP2-immunoreactive proteins were present
      in both circular and longitudinal myometrial cells. Finally, Kv4.2 and KChIP2
      mRNA levels were similarly elevated in pregnant and nonpregnant corpora of one
      side-conceived rats. These results suggest that diffusible factors coordinate the
      pregnancy-associated changes in molecular compositions of myometrial Kv4-KChIP
      channel complexes.

PMID- 15454399
TI  - Heart-type fatty acid-binding protein reciprocally regulates glucose and fatty
      acid utilization during exercise.
AB  - The role of heart-type cytosolic fatty acid-binding protein (H-FABP) in mediating
      whole body and muscle-specific long-chain fatty acid (LCFA) and glucose
      utilization was examined using exercise as a phenotyping tool. Catheters were
      chronically implanted in a carotid artery and jugular vein of wild-type (WT, n =
      8), heterozygous (H-FABP(+/-), n = 8), and null (H-FABP(-/-), n = 7) chow-fed
      C57BL/6J mice, and mice were allowed to recover for 7 days. After a 5-h fast,
      conscious, unrestrained mice were studied during 30 min of treadmill exercise
      (0.6 mph). A bolus of [(125)I]-15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid
      and 2-deoxy-[(3)H]glucose was administered to obtain rates of whole body
      metabolic clearance (MCR) and indexes of muscle LCFA (R(f)) and glucose (R(g))
      utilization. Fasting, nonesterified fatty acids (mM) were elevated in H-FABP(-/-)
      mice (2.2 +/- 0.9 vs. 1.3 +/- 0.1 and 1.3 +/- 0.2 for WT and H-FABP(+/-)). During
      exercise, blood glucose (mM) increased in WT (11.7 +/- 0.8) and H-FABP(+/-) (12.6
      +/- 0.9) mice, whereas H-FABP(-/-) mice developed overt hypoglycemia (4.8 +/-
      0.8). Examination of tissue-specific and whole body glucose and LCFA utilization
      demonstrated a dependency on H-FABP with exercise in all tissues examined.
      Reductions in H-FABP led to decreasing exercise-stimulated R(f) and increasing
      R(g) with the most pronounced effects in heart and soleus muscle. Similar results
      were seen for MCR with decreasing LCFA and increasing glucose clearance with
      declining levels of H-FABP. These results show that, in vivo, H-FABP has
      reciprocal effects on glucose and LCFA utilization and whole body fuel
      homeostasis when metabolic demands are elevated by exercise.

PMID- 15454400
TI  - Acetyl-CoA provision and the acetyl group deficit at the onset of contraction in
      ischemic canine skeletal muscle.
AB  - We examined the effects of increasing acetylcarnitine and acetyl-CoA availability
      at rest, independent of pyruvate dehydrogenase complex (PDC) activation, on
      energy production and tension development during the rest-to-work transition in
      canine skeletal muscle. We aimed to elucidate whether the lag in PDC-derived
      acetyl-CoA delivery toward the TCA cycle at the onset of exercise can be overcome
      by increasing acetyl group availability independently of PDC activation or is
      intimately dependent on PDC-derived acetyl-CoA. Gracilis muscle pretreated with
      saline or sodium acetate (360 mg/kg body mass) (both n = 6) was sampled
      repeatedly during 5 min of ischemic contraction. Acetate increased
      acetylcarnitine and acetyl-CoA availability (both P < 0.01) above control at rest
      and throughout contraction (P < 0.05), independently of differences in resting
      PDC activation between treatments. Acetate reduced oxygen-independent ATP
      resynthesis approximately 40% (P < 0.05) during the first minute of contraction.
      No difference in oxygen-independent ATP resynthesis existed between treatments
      from 1 to 3 min of contraction; however, energy production via this route
      increased approximately 25% (P < 0.05) above control in the acetate-treated group
      during the final 2 min of contraction. Tension development was approximately 20%
      greater after 5-min contraction after acetate treatment than in control (P <
      0.05). In conclusion, at the immediate onset of contraction, when PDC was largely
      inactive, increasing cellular acetyl group availability overcame inertia in
      mitochondrial ATP regeneration. However, after the first minute, when PDC was
      near maximally activated in both groups, it appears that PDC-derived acetyl-CoA,
      rather than increased cellular acetyl group availability per se, dictated
      mitochondrial ATP resynthesis.

PMID- 15454401
TI  - Effects of two familial hypertrophic cardiomyopathy mutations in alpha
      tropomyosin, Asp175Asn and Glu180Gly, on the thermal unfolding of actin-bound
      tropomyosin.
AB  - Differential scanning calorimetry was used to investigate the thermal unfolding
      of native alpha-tropomyosin (Tm), wild-type alpha-Tm expressed in Escherichia
      coli and the wild-type alpha-Tm carrying either of two missense mutations
      associated with familial hypertrophic cardiomyopathy, D175N or E180G. Recombinant
      alpha-Tm was expressed with an N-terminal Ala-Ser extension to substitute for the
      essential N-terminal acetylation of the native Tm. Native and Ala-Ser-Tm were
      indistinguishable in our assays. In the absence of F-actin, the thermal unfolding
      of Tm was reversible and the heat sorption curve of Tm with Cys-190 reduced was
      decomposed into two separate calorimetric domains with maxima at approximately 42
      and 51 degrees C. In the presence of phalloidin-stabilized F-actin, a new
      cooperative transition appears at 46-47 degrees C and completely disappears after
      the irreversible denaturation of F-actin. A good correlation was found to exist
      between the maximum of this peak and the temperature of half-maximal dissociation
      of the F-actin/Tm complex as determined by light scattering experiments. We
      conclude that Tm thermal denaturation only occurs upon its dissociation from F
      actin. In the presence of F-actin, D175N alpha-Tm shows a melting profile and
      temperature dependence of dissociation from F-actin similar to those for wild
      type alpha-Tm. The actin-induced stabilization of E180G alpha-Tm is significantly
      less than for wild-type alpha-Tm and D175N alpha-Tm, and this property could
      contribute to the more severe myopathy phenotype reported for this mutation.

PMID- 15454402
TI  - Room temperature spectrally resolved single-molecule spectroscopy reveals new
      spectral forms and photophysical versatility of aequorea green fluorescent
      protein variants.
AB  - It is known from ensemble spectroscopy at cryogenic temperatures that variants of
      the Aequorea green fluorescent protein (GFP) occur in interconvertible
      spectroscopically distinct forms which are obscured in ensemble room temperature
      spectroscopy. By analyzing the fluorescence of the GFP variants EYFP and EGFP by
      spectrally resolved single-molecule spectroscopy we were able to observe
      spectroscopically different forms of the proteins and to dynamically monitor
      transitions between these forms at room temperature. In addition to the
      predominant EYFP B-form we have observed the blue-shifted I-form thus far only
      seen at cryogenic temperatures and have followed transitions between these forms.
      Further we have identified for EYFP and for EGFP three more, so far unknown,
      forms with red-shifted fluorescence. Transitions between the predominant forms
      and the red-shifted forms show a dark time which indicates the existence of a
      nonfluorescent intermediate. The spectral position of the newly-identified red
      shifted forms and their formation via a nonfluorescent intermediate hint that
      these states may account for the possible photoactivation observed in bulk
      experiments. The comparison of the single-protein spectra of the red-shifted EYFP
      and EGFP forms with single-molecule fluorescence spectra of DsRed suggest that
      these new forms possibly originate from an extended chromophoric pi-system
      analogous to the DsRed chromophore.

PMID- 15454403
TI  - Controlled ablation of microtubules using a picosecond laser.
AB  - The use of focused high-intensity light sources for ablative perturbation has
      been an important technique for cell biological and developmental studies. In
      targeting subcellular structures many studies have to deal with the inability to
      target, with certainty, an organelle or large macromolecular complex. Here we
      demonstrate the ability to selectively target microtubule-based structures with a
      laser microbeam through the use of enhanced yellow fluorescent protein (EYFP) and
      enhanced cyan fluorescent protein (ECFP) variants of green fluorescent protein
      fusions of tubule. Potorous tridactylus (PTK2) cell lines were generated that
      stably express EYFP and ECFP tagged to the alpha-subunit of tubulin. Using
      microtubule fluorescence as a guide, cells were irradiated with picosecond laser
      pulses at discrete microtubule sites in the cytoplasm and the mitotic spindle.
      Correlative thin-section transmission electron micrographs of cells fixed one
      second after irradiation demonstrated that the nature of the ultrastructural
      damage appeared to be different between the EYFP and the ECFP constructs
      suggesting different photon interaction mechanisms. We conclude that focal
      disruption of single cytoplasmic and spindle microtubules can be precisely
      controlled by combining laser microbeam irradiation with different fluorescent
      fusion constructs. The possible photon interaction mechanisms are discussed in
      detail.

PMID- 15454404
TI  - More than a monolayer: relating lung surfactant structure and mechanics to
      composition.
AB  - Survanta, a clinically used bovine lung surfactant extract, in contact with
      surfactant in the subphase, shows a coexistence of discrete monolayer islands of
      solid phase coexisting with continuous multilayer "reservoirs" of fluid phase
      adjacent to the air-water interface. Exchange between the monolayer, the
      multilayer reservoir, and the subphase determines surfactant mechanical
      properties such as the monolayer collapse pressure and surface viscosity by
      regulating solid-fluid coexistence. Grazing incidence x-ray diffraction shows
      that the solid phase domains consist of two-dimensional crystals similar to those
      formed by mixtures of dipalmitoylphosphatidylcholine and palmitic acid. The
      condensed domains grow as the surface pressure is increased until they coalesce,
      trapping protrusions of liquid matrix. At approximately 40 mN/m, a plateau exists
      in the isotherm at which the solid phase fraction increases from approximately 60
      to 90%, at which the surface viscosity diverges. The viscosity is driven by the
      percolation of the solid phase domains, which depends on the solid phase area
      fraction of the monolayer. The high viscosity may lead to high monolayer collapse
      pressures, help prevent atelectasis, and minimize the flow of lung surfactant out
      of the alveoli due to surface tension gradients.

PMID- 15454405
TI  - MAPK cascade possesses decoupled controllability of signal amplification and
      duration.
AB  - The three important characteristics of the output signal of mitogen activated
      protein kinase (MAPK) cascade are time delay between stimulus and response,
      amplitude gain, and duration of the output signal. In this study, we performed a
      sensitivity analysis on the computational model of epidermal growth factor
      receptor (EGFR) activated MAPK cascade developed by Schoeberl and co-workers (1)
      to identify the sensitive steps of the pathway affecting these characteristics.
      We show that the signaling network is sensitive in a decoupled manner, which
      provides the ability to control its output amplitude and duration one at a time.
      Signal duration is found sensitive only to the phosphatase reactions at the MEK
      level. In contrast, signal amplitude is found most sensitive to the phosphatase
      reactions at the ERK level. Time delay is found to be a robust characteristic of
      the system.

PMID- 15454406
TI  - Which is better for cDNA-microarray-based classification: ratios or direct
      intensities.
AB  - MOTIVATION: There are two general methods for making gene-expression microarrays:
      one is to hybridize a single test set of labeled targets to the probe, and
      measure the background-subtracted intensity at each probe site; the other is to
      hybridize both a test and a reference set of differentially labeled targets to a
      single detector array, and measure the ratio of the background-subtracted
      intensities at each probe site. Which method is better depends on the variability
      in the cell system and the random factors resulting from the microarray
      technology. It also depends on the purpose for which the microarray is being
      used. Classification is a fundamental application and it is the one considered
      here. RESULTS: This paper describes a model-based simulation paradigm that
      compares the classification accuracy provided by these methods over a variety of
      noise types and presents the results of a study modeled on noise typical of cDNA
      microarray data. The model consists of four parts: (1) the measurement equation
      for genes in the reference state; (2) the measurement equation for genes in the
      test state; (3) the ratio and normalization procedure for a dual-channel system;
      and (4) the intensity and normalization procedure for a single-channel system. In
      the reference state, the mean intensities are modeled as a shifted exponential
      distribution, and the intensity for a particular gene is modeled via a normal
      distribution, Normal(I, alphaI), about its mean intensity I, with alpha being the
      coefficient of variation of the cell system. In the test state, some genes have
      their intensities up-regulated by a random factor. The model includes a number of
      random factors affecting intensity measurement: deposition gain d, labeling gain,
      and post-image-processing residual noise. The key conclusion resulting from the
      study is that the coefficient of variation governing the randomness of the
      intensities and the deposition gain are the most important factors for
      determining whether a single-channel or dual-channel system provides superior
      classification, and the decision region in the alpha-d plane is approximately
      linear.

PMID- 15454407
TI  - CIS: compound importance sampling method for protein-DNA binding site p-value
      estimation.
AB  - MOTIVATION: A key aspect of transcriptional regulation is the binding of
      transcription factors to sequence-specific binding sites that allow them to
      modulate the expression of nearby genes. Given models of such binding sites, one
      can scan regulatory regions for putative binding sites and construct a genome
      wide regulatory network. In such genome-wide scans, it is crucial to control the
      amount of false positive predictions. Recently, several works demonstrated the
      benefits of modeling dependencies between positions within the binding site. Yet,
      computing the statistical significance of putative binding sites in this scenario
      remains a challenge. RESULTS: We present a general, accurate and efficient method
      for computing p-values of putative binding sites that is applicable to a large
      class of probabilistic binding site and background models. We demonstrate the
      accuracy of the method on synthetic and real-life data. AVAILABILITY: The
      procedure for scanning DNA sequences and computing the statistical significance
      of putative binding site scores is available upon request at
      http://compbio.cs.huji.ac.il/CIS/ CONTACT: nir@cs.huji.ac.il.

PMID- 15454408
TI  - A graph-theoretic approach for the separation of b and y ions in tandem mass
      spectra.
AB  - MOTIVATION: Ion-type identification is a fundamental problem in computational
      proteomics. Methods for accurate identification of ion types provide the basis
      for many mass spectrometry data interpretation problems, including (a) de novo
      sequencing, (b) identification of post-translational modifications and mutations
      and (c) validation of database search results. RESULTS: Here, we present a novel
      graph-theoretic approach for solving the problem of separating b ions from y ions
      in a set of tandem mass spectra. We represent each spectral peak as a node and
      consider two types of edges: type-1 edge connecting two peaks probably of the
      same ion types and type-2 edge connecting two peaks probably of different ion
      types. The problem of ion-separation is formulated and solved as a graph
      partition problem, which is to partition the graph into three subgraphs,
      representing b, y and others ions, respectively, through maximizing the total
      weight of type-1 edges while minimizing the total weight of type-2 edges within
      each partitioned subgraph. We have developed a dynamic programming algorithm for
      rigorously solving this graph partition problem and implemented it as a computer
      program PRIME (PaRtition of Ion types in tandem Mass spEctra). The tests on a
      large amount of simulated mass spectra and 19 sets of high-quality experimental
      Fourier transform ion cyclotron resonance tandem mass spectra indicate that an
      accuracy level of approximately 90% for the separation of b and y ions was
      achieved. AVAILABILITY: The executable code of PRIME is available upon request.
      CONTACT: xyn@bmb.uga.edu.

PMID- 15454409
TI  - Modelling cellular systems with PySCeS.
AB  - The Python Simulator for Cellular Systems (PySCeS) is an extendable research tool
      for the numerical analysis and investigation of cellular systems. AVAILABILITY:
      PySCeS is distributed as Open Source Software under the GNU General Public
      Licence and is available for download from http://pysces.sourceforge.net CONTACT:
      bgoli@sun.ac.za.

PMID- 15454410
TI  - Improving promoter prediction for the NNPP2.2 algorithm: a case study using
      Escherichia coli DNA sequences.
AB  - MOTIVATION: Although a great deal of research has been undertaken in the area of
      promoter prediction, prediction techniques are still not fully developed. Many
      algorithms tend to exhibit poor specificity, generating many false positives, or
      poor sensitivity. The neural network prediction program NNPP2.2 is one such
      example. RESULTS: To improve the NNPP2.2 prediction technique, the distance
      between the transcription start site (TSS) associated with the promoter and the
      translation start site (TLS) of the subsequent gene coding region has been
      studied for Escherichia coli K12 bacteria. An empirical probability distribution
      that is consistent for all E.coli promoters has been established. This
      information is combined with the results from NNPP2.2 to create a new technique
      called TLS-NNPP, which improves the specificity of promoter prediction. The
      technique is shown to be effective using E.coli DNA sequences, however, it is
      applicable to any organism for which a set of promoters has been experimentally
      defined. AVAILABILITY: The data used in this project and the prediction results
      for the tested sequences can be obtained from
      http://www.uow.edu.au/~yanxia/E_Coli_paper/SBurden_Results.xls CONTACT:
      alh98@uow.edu.au.

PMID- 15454411
TI  - Seq2Struct: a resource for establishing sequence-structure links.
AB  - Several methods for establishing cross-links between Protein Data Bank (PDB)
      structures or Structural Classification of Proteins (SCOP) domains and Swiss-Prot
      + TrEMBL sequences (or vice versa) rely on database annotations. Alternatively,
      sequence alignment procedures can be used. In this study, we describe Seq2Struct,
      a web resource for the identification of sequence-structure links. The resource
      consists of an exhaustive collection of annotated links between Swiss-Prot +
      TrEMBL and PDB + SCOP database entries. Links are based on pre-established highly
      reliable thresholds and stored in a relational database, which has been enhanced
      using annotations derived from Swiss-Prot, PDB, SCOP, GOA and DSSP databases. The
      Seq2Struct database contents, supported by a WWW web interface, can be queried
      both online and downloaded. AVAILABILITY: The Seq2Struct resource, with related
      documentation, is available at http://surface.bio.uniroma2.it/seq2struct/
      CONTACT: seq2struct@cbm.bio.uniroma2.it.

PMID- 15454412
TI  - Weighted analysis of microarray gene expression using maximum-likelihood.
AB  - MOTIVATION: The numerical values of gene expression measured using microarrays
      are usually presented to the biological end-user as summary statistics of spot
      pixel data, such as the spot mean, median and mode. Much of the subsequent data
      analysis reported in the literature, however, uses only one of these spot
      statistics. This results in sub-optimal estimates of gene expression levels and a
      need for improvement in quantitative spot variation surveillance. RESULTS: This
      paper develops a maximum-likelihood method for estimating gene expression using
      spot mean, variance and pixel number values available from typical microarray
      scanners. It employs a hierarchical model of variation between and within
      microarray spots. The hierarchical maximum-likelihood estimate (MLE) is shown to
      be a more efficient estimator of the mean than the 'conventional' estimate using
      solely the spot mean values (i.e. without spot variance data). Furthermore, under
      the assumptions of our model, the spot mean and spot variance are shown to be
      sufficient statistics that do not require the use of all pixel data. The
      hierarchical MLE method is applied to data from both Monte Carlo (MC) simulations
      and a two-channel dye-swapped spotted microarray experiment. The MC simulations
      show that the hierarchical MLE method leads to improved detection of differential
      gene expression particularly when 'outlier' spots are present on the arrays.
      Compared with the conventional method, the MLE method applied to data from the
      microarray experiment leads to an increase in the number of differentially
      expressed genes detected for low cut-off P-values of interest.

PMID- 15454413
TI  - arrayMagic: two-colour cDNA microarray quality control and preprocessing.
AB  - arrayMagic is a software package for quality control and preprocessing of two
      colour cDNA microarray data. The automated analysis pipeline comprises data
      import, normalization, replica merging, quality diagnostics and data export. The
      script-based processing combines reproducibility and flexibility at high
      throughput and provides quality-assured and preprocessed microarray data to high
      level follow-up analysis. AVAILABILITY: The R package arrayMagic is available
      with BSD license at http://www.bioconductor.org CONTACT: a.buness@dkfz.de
      SUPPLEMENTARY INFORMATION: The package contains documentation in the form of
      manual pages and a vignette with a guided tour of a typical workflow.

PMID- 15454414
TI  - An efficient Monte Carlo approach to assessing statistical significance in
      genomic studies.
AB  - MOTIVATION: Multiple hypothesis testing is a common problem in genome research,
      particularly in microarray experiments and genomewide association studies.
      Failure to account for the effects of multiple comparisons would result in an
      abundance of false positive results. The Bonferroni correction and Holm's step
      down procedure are overly conservative, whereas the permutation test is time
      consuming and is restricted to simple problems. RESULTS: We developed an
      efficient Monte Carlo approach to approximating the joint distribution of the
      test statistics along the genome. We then used the Monte Carlo distribution to
      evaluate the commonly used criteria for error control, such as familywise error
      rates and positive false discovery rates. This approach is applicable to any data
      structures and test statistics. Applications to simulated and real data
      demonstrate that the proposed approach provides accurate error control, and can
      be substantially more powerful than the Bonferroni and Holm methods, especially
      when the test statistics are highly correlated.

PMID- 15454415
TI  - Transmembrane peptide-induced lipid sorting and mechanism of Lalpha-to-inverted
      phase transition using coarse-grain molecular dynamics.
AB  - Molecular dynamics results are presented for a coarse-grain model of 1,2-di-n
      alkanoyl-sn-glycero-3-phosphocholine, water, and a capped cylindrical model of a
      transmembrane peptide. We first demonstrate that different alkanoyl-length lipids
      are miscible in the liquid-disordered lamellar (Lalpha) phase. The transmembrane
      peptide is constructed of hydrophobic sites with hydrophilic caps. The
      hydrophobic length of the peptide is smaller than the hydrophobic thickness of a
      bilayer consisting of an equal mixture of long and short alkanoyl tail lipids.
      When incorporated into the membrane, a meniscus forms in the vicinity of the
      peptide and the surrounding area is enriched in the short lipid. The meniscus
      region draws water into it. In the regions that are depleted of water, the
      bilayers can fuse. The lipid headgroups then rearrange to solvate the newly
      formed water pores, resulting in an inverted phase. This mechanism appears to be
      a viable pathway for the experimentally observed Lalpha-to-inverse hexagonal
      (HII) peptide-induced phase transition.

PMID- 15454416
TI  - Models of the structure and voltage-gating mechanism of the shaker K+ channel.
AB  - In the preceding, accompanying article, we present models of the structure and
      voltage-dependent gating mechanism of the KvAP bacterial K+ channel that are
      based on three types of evidence: crystal structures of portions of the KvAP
      protein, theoretical modeling criteria for membrane proteins, and biophysical
      studies of the properties of native and mutated voltage-gated channels. Most of
      the latter experiments were performed on the Shaker K+ channel. Some of these
      data are difficult to relate directly to models of the KvAP channel's structure
      due to differences in the Shaker and KvAP sequences. We have dealt with this
      problem by developing new models of the structure and gating mechanism of the
      transmembrane and extracellular portions of the Shaker channel. These models are
      consistent with almost all of the biophysical data. In contrast, much of the
      experimental data are incompatible with the "paddle" model of gating that was
      proposed when the KvAP crystal structures were first published. The general
      folding pattern and gating mechanisms of our current models are similar to some
      of our earlier models of the Shaker channel.

PMID- 15454417
TI  - Geometric and material determinants of patterning efficiency by
      dielectrophoresis.
AB  - Dielectrophoretic (DEP) forces have been used extensively to manipulate,
      separate, and localize biological cells and bioparticles via high-gradient
      electric fields. However, minimization of DEP exposure time is desirable, because
      of possible untoward effects on cell behavior. Toward this goal, this article
      investigates the geometric and material determinants of particle patterning
      kinetics and efficiency. In particular, the time required to achieve a steady
      state pattern is theoretically modeled and experimentally validated for a planar,
      interdigitated bar electrode array energized in a standing-wave configuration.
      This measure of patterning efficiency is calculated from an improved Fourier
      series solution of DEP force, in which realistic boundary conditions and a finite
      chamber height are imposed to reflect typical microfluidic applications. The
      chamber height, electrode spacing, and fluid viscosity and conductivity are
      parameters that profoundly affect patterning efficiency, and optimization can
      reduce electric field exposure by orders of magnitude. Modeling strategies are
      generalizable to arbitrary electrode design as well as to conditions where DEP
      force may not act alone to cause particle motion. This improved understanding of
      DEP patterning kinetics provides a framework for new advances in the development
      of DEP-based biological devices and assays with minimal perturbation of cell
      behavior.

PMID- 15454418
TI  - Torque generation by the Fo motor of the sodium ATPase.
AB  - Based on recent structural and functional findings, we have constructed a
      mathematical model for the sodium-driven Fo motor of the F1Fo-ATPase from the
      anaerobic bacterium Propionigenium modestum. The model reveals the
      mechanochemical principles underlying the Fo motor's operation, and explains all
      of the existing experimental data on wild-type and mutant Fo motors. In
      particular, the model predicts a nonmonotonic dependence of the ATP hydrolysis
      activity on the sodium concentration, a prediction confirmed by new experiments.
      To explain experimental observations, the positively charged stator residue
      (R227) must assume different positions in the ATP synthesis and hydrolysis
      directions. This work also illustrates how to extract a motor mechanism from
      dynamical experimental observations in the absence of complete structural
      information.

PMID- 15454419
TI  - The complex kinetics of protein folding in wide temperature ranges.
AB  - The complex protein folding kinetics in wide temperature ranges is studied
      through diffusive dynamics on the underlying energy landscape. The well-known
      kinetic chevron rollover behavior is recovered from the mean first passage time,
      with the U-shape dependence on temperature. The fastest folding temperature T0 is
      found to be smaller than the folding transition temperature Tf. We found that the
      fluctuations of the kinetics through the distribution of first passage time show
      rather universal behavior, from high-temperature exponential Poissonian kinetics
      to the relatively low-temperature highly non-exponential kinetics. The transition
      temperature is at Tk and T0 < Tk < Tf. In certain low-temperature regimes, a
      power law behavior at long time emerges. At very low temperatures (lower than
      trapping transition temperature T < T0/(4 approximately 6)), the kinetics is an
      exponential Poissonian process again.

PMID- 15454420
TI  - Uniform sampling of steady-state flux spaces: means to design experiments and to
      interpret enzymopathies.
AB  - Reconstruction of genome-scale metabolic networks is now possible using multiple
      different data types. Constraint-based modeling is an approach to interrogate
      capabilities of reconstructed networks by constraining possible cellular behavior
      through the imposition of physicochemical laws. As a result, a steady-state flux
      space is defined that contains all possible functional states of the network.
      Uniform random sampling of the steady-state flux space allows for the unbiased
      appraisal of its contents. Monte Carlo sampling of the steady-state flux space of
      the reconstructed human red blood cell metabolic network under simulated
      physiologic conditions yielded the following key results: 1), probability
      distributions for the values of individual metabolic fluxes showed a wide variety
      of shapes that could not have been inferred without computation; 2), pairwise
      correlation coefficients were calculated between all fluxes, determining the
      level of independence between the measurement of any two fluxes, and identifying
      highly correlated reaction sets; and 3), the network-wide effects of the change
      in one (or a few) variables (i.e., a simulated enzymopathy or fixing a flux range
      based on measurements) were computed. Mathematical models provide the most
      compact and informative representation of a hypothesis of how a cell works. Thus,
      understanding model predictions clearly is vital to driving forward the iterative
      model-building procedure that is at the heart of systems biology. Taken together,
      the Monte Carlo sampling procedure provides a broadening of the constraint-based
      approach by allowing for the unbiased and detailed assessment of the impact of
      the applied physicochemical constraints on a reconstructed network.

PMID- 15454421
TI  - Downhill kinetics of biomolecular interface binding: globally connected scenario.
AB  - We study the kinetics of the biomolecular binding process at the interface using
      energy landscape theory. The global kinetic connectivity case is considered for a
      downhill funneled energy landscape. By solving the kinetic master equation, the
      kinetic time for binding is obtained and shown to have a U-shape curve-dependence
      on the temperature. The kinetic minimum of the binding time monotonically
      decreases when the ratio of the underlying energy gap between native state and
      average non-native states versus the roughness or the fluctuations of the
      landscape increases. At intermediate temperatures, fluctuations measured by the
      higher moments of the binding time lead to non-Poissonian, non-exponential
      kinetics. At both high and very low temperatures, the kinetics is nearly
      Poissonian and exponential.

PMID- 15454422
TI  - Optimizing genetic circuits by global sensitivity analysis.
AB  - Artificial genetic circuits are becoming important tools for controlling cellular
      behavior and studying molecular biosystems. To genetically optimize the
      properties of complex circuits in a practically feasible fashion, it is necessary
      to identify the best genes and/or their regulatory components as mutation targets
      to avoid the mutation experiments being wasted on ineffective regions, but this
      goal is generally not achievable by current methods. The Random Sampling-High
      Dimensional Model Representation (RS-HDMR) algorithm is employed in this work as
      a global sensitivity analysis technique to estimate the sensitivities of the
      circuit properties with respect to the circuit model parameters, such as rate
      constants, without knowing the precise parameter values. The sensitivity
      information can then guide the selection of the optimal mutation targets and
      thereby reduce the laboratory effort. As a proof of principle, the in vivo
      effects of 16 pairwise mutations on the properties of a genetic inverter were
      compared against the RS-HDMR predictions, and the algorithm not only showed good
      consistency with laboratory results but also revealed useful information, such as
      different optimal mutation targets for optimizing different circuit properties,
      not available from previous experiments and modeling.

PMID- 15454423
TI  - Conformational flexibility of the MHC class I alpha1-alpha2 domain in peptide
      bound and free states: a molecular dynamics simulation study.
AB  - Major histocompatibility complex class I proteins play a key role in the
      recognition and presentation of peptide antigens to the host immune system. The
      structure of various major histocompatibility complex class I proteins has been
      determined experimentally in complex with several antigenic peptides. However,
      the structure in the unbound (empty) form is not known. To study the
      conformational dynamics of the empty major histocompatibility complex class I
      molecule comparative molecular dynamics simulations have been performed starting
      from the crystal structure of a peptide bound class I peptide-binding domain in
      the presence and absence of a peptide ligand. Simulations including the bound
      peptide stayed close to the experimental start structure at both simulation
      temperatures (300 and 355 K) during the entire simulation of 26 ns. Several
      independent simulations in the absence of peptide indicate that the empty domain
      may not adopt a single defined conformation but is conformationally significantly
      more heterogeneous in particular within the alpha-helices that flank the peptide
      binding cleft. The calculated conformational dynamics along the protein chain
      correlate well with available spectroscopic data and with the observed site
      specific sensitivity of the empty class I protein to proteolytic digestion.
      During the simulations at 300 K the binding region for the peptide N-terminus
      stayed close to the conformation in the bound state, whereas the anchor region
      for the C-terminus showed significantly larger conformational fluctuations. This
      included a segment at the beginning of the second alpha-helix in the domain that
      is likely to be involved in the interaction with the chaperone protein tapasin
      during the peptide-loading process. The simulation studies further indicate that
      peptide binding at the C- and N-terminus may follow different mechanisms that
      involve different degrees of induced conformational changes in the peptide
      binding domain. In particular binding of the peptide C-terminus may require
      conformational stabilization by chaperone proteins during peptide loading.

PMID- 15454424
TI  - Effects of the geometry of the immunological synapse on the delivery of effector
      molecules.
AB  - Recent experiments focusing on the function of the immunological synapse formed
      between a T cell and an antigen-presenting cell raise many questions about its
      purpose. We examine the proposal that the close apposition of the cell membranes
      in the central region of the synapse acts to focus T-cell secretions on the
      target cell, thus reducing the effect on nearby cells. We show that the
      efficiency of targeted T-cell responses to closely apposed cells is only weakly
      dependent on the distance between the cells. We also calculate effective
      (diffusion-limited) rates of binding and unbinding for molecules secreted within
      the synapse. We apply our model to the stimulation of B cells by secreted
      interleukin-4 (IL-4), and find that very few molecules of IL-4 need be released
      to essentially saturate the IL-4 receptors on the B-cell surface.

PMID- 15454425
TI  - Studies of proton translocations in biological systems: simulating proton
      transport in carbonic anhydrase by EVB-based models.
AB  - Proton transport (PTR) processes play a major role in bioenergetics and thus it
      is important to gain a molecular understanding of these processes. At present the
      detailed description of PTR in proteins is somewhat unclear and it is important
      to examine different models by using well-defined experimental systems. One of
      the best benchmarks is provided by carbonic anhydrase III (CA III), because this
      is one of the few systems where we have a clear molecular knowledge of the rate
      constant of the PTR process and its variation upon mutations. Furthermore, this
      system transfers a proton between several water molecules, thus making it highly
      relevant to a careful examination of the "proton wire" concept. Obtaining a
      correlation between the structure of this protein and the rate of the PTR process
      should help to discriminate between alternative models and to give useful clues
      about PTR processes in other systems. Obviously, obtaining such a correlation
      requires a correct representation of the "chemistry" of PTR between different
      donors and acceptors, as well as the ability to evaluate the free energy barriers
      of charge transfer in proteins, and to simulate long-time kinetic processes. The
      microscopic empirical valence bond (Warshel, A., and R. M. Weiss. 1980. J. Am.
      Chem. Soc. 102:6218-6226; and Aqvist, J., and A. Warshel. 1993. Chem. Rev.
      93:2523-2544) provides a powerful way for representing the chemistry and
      evaluating the free energy barriers, but it cannot be used with the currently
      available computer times in direct simulation of PTR with significant activation
      barriers. Alternatively, one can reduce the empirical valence bond (EVB) to the
      modified Marcus' relationship and use semimacroscopic electrostatic calculations
      plus a master equation to determine the PTR kinetics (Sham, Y., I. Muegge, and A.
      Warshel. 1999. Proteins. 36:484-500). However, such an approximation does not
      provide a rigorous multisite kinetic treatment. Here we combine the useful
      ingredients of both approaches and develop a simplified EVB effective potential
      that treats explicitly the chain of donors and acceptors while considering
      implicitly the rest of the protein/solvent system. This approach can be used in
      Langevin dynamics simulations of long-time PTR processes. The validity of our new
      simplified approach is demonstrated first by comparing its Langevin dynamics
      results for a PTR along a chain of water molecules in water to the corresponding
      molecular dynamics simulations of the fully microscopic EVB model. This study
      examines dynamics of both models in cases of low activation barriers and the
      dependence of the rate on the energetics for cases with moderate barriers. The
      study of the dependence on the activation barrier is next extended to the range
      of higher barriers, demonstrating a clear correlation between the barrier height
      and the rate constant. The simplified EVB model is then examined in studies of
      the PTR in carbonic anhydrase III, where it reproduces the relevant experimental
      results without the use of any parameter that is specifically adjusted to fit the
      energetics or dynamics of the reaction in the protein. We also validate the
      conclusions obtained previously from the EVB-based modified Marcus' relationship.
      It is concluded that this approach and the EVB-based model provide a reliable,
      effective, and general tool for studies of PTR in proteins. Finally in view of
      the behavior of the simulated result, in both water and the CA III, we conclude
      that the rate of PTR in proteins is determined by the electrostatic energy of the
      transferred proton as long as this energy is higher than a few kcal/mol.

PMID- 15454426
TI  - How does averaging affect protein structure comparison on the ensemble level?
AB  - Recent algorithmic advances and continual increase in computational power have
      made it possible to simulate protein folding and dynamics on the level of
      ensembles. Furthermore, analyzing protein structure by using ensemble
      representation is intrinsic to certain experimental techniques, such as nuclear
      magnetic resonance. This creates a problem of how to compare an ensemble of
      molecules with a given reference structure. Recently, we used distance-based root
      mean-square deviation (dRMS) to compare the native structure of a protein with
      its unfolded-state ensemble. We showed that for small, mostly alpha-helical
      proteins, the mean unfolded-state Calpha-Calpha distance matrix is significantly
      more nativelike than the Calpha-Calpha matrices corresponding to the individual
      members of the unfolded ensemble. Here, we give a mathematical derivation that
      shows that, for any ensemble of structures, the dRMS deviation between the
      ensemble-averaged distance matrix and any given reference distance matrix is
      always less than or equal to the average dRMS deviation of the individual members
      of the ensemble from the same reference matrix. This holds regardless of the
      nature of the reference structure or the structural ensemble in question. In
      other words, averaging of distance matrices can only increase their level of
      similarity to a given reference matrix, relative to the individual matrices
      comprising the ensemble. Furthermore, we show that the above inequality holds in
      the case of Cartesian coordinate-based root-mean-square deviation as well. We
      discuss this in the context of our proposal that the average structure of the
      unfolded ensemble of small helical proteins is close to the native structure, and
      demonstrate that this finding goes beyond the above mathematical fact.

PMID- 15454427
TI  - Osmophobic effect of glycerol on irreversible thermal denaturation of rabbit
      creatine kinase.
AB  - Protein stability plays an extremely important role not only in its biological
      function but also in medical science and protein engineering. Osmolytes provide a
      general method to protect proteins from the unfolding and aggregation induced by
      extreme environmental stress. In this study, the effect of glycerol on protection
      of the model enzyme creatine kinase (CK) against heat stress was investigated by
      a combination of spectroscopic method and thermodynamic analysis. Glycerol could
      prevent CK from thermal inactivation and aggregation in a concentration-dependent
      manner. The spectroscopic measurements suggested that the protective effect of
      glycerol was a result of enhancing the structural stability of native CK. A
      further thermodynamic analysis using the activated-complex theory suggested that
      the effect of glycerol on preventing CK against aggregation was consistent with
      those previously established mechanisms in reversible systems. The osmophobic
      effect of glycerol, which preferentially raised the free energy of the activated
      complex, shifted the equilibrium between the native state and the activated
      complex in favor of the native state. A comparison of the inactivation rate and
      the denaturation rate suggested that the protection of enzyme activity by
      glycerol should be attributed to the enhancement of the structural stability of
      the whole protein rather than the flexible active site.

PMID- 15454428
TI  - A model of voltage gating developed using the KvAP channel crystal structure.
AB  - Having inspected the crystal structure of the complete KvAP channel protein, we
      suspect that the voltage-sensing domain is too distorted to provide reliable
      information about its native tertiary structure or its interactions with the
      central pore-forming domain. On the other hand, a second crystal structure of the
      isolated voltage-sensing domain may well correspond to a native open
      conformation. We also observe that the paddle model of gating developed from
      these two structures is inconsistent with many experimental results, and suspect
      it to be energetically unrealistic. Here we show that the isolated voltage
      sensing domain crystal structure can be docked onto the pore domain portion of
      the full-length KvAP crystal structure in an energetically favorable way to
      create a model of the open conformation. Using this as a starting point, we have
      developed rather conventional models of resting and transition conformations
      based on the helical screw mechanism for the transition from the open to the
      resting conformation. Our models are consistent with both theoretical
      considerations and experimental results.

PMID- 15454429
TI  - Asymmetry in membrane responses to electric shocks: insights from bidomain
      simulations.
AB  - Models of myocardial membrane dynamics have not been able to reproduce the
      experimentally observed negative bias in the asymmetry of transmembrane potential
      changes (DeltaVm) induced by strong electric shocks delivered during the action
      potential plateau. The goal of this study is to determine what membrane model
      modifications can bridge this gap between simulation and experiment. We conducted
      simulations of shocks in bidomain fibers and sheets with membrane dynamics
      represented by the LRd'2000 model. We found that in the fiber, the negative bias
      in DeltaVm asymmetry could not be reproduced by addition of electroporation only,
      but by further addition of hypothetical outward current, Ia, activated upon
      strong shock-induced depolarization. Furthermore, the experimentally observed
      rectangularly shaped positive DeltaVm, negative-to-positive DeltaVm ratio
      (asymmetry ratio) = approximately 2, electroporation occurring at the anode only,
      and the increase in positive DeltaVm caused by L-type Ca2+-channel blockade were
      reproduced in the strand only if Ia was assumed to be a part of K+ flow through
      the L-type Ca2+-channel. In the sheet, Ia not only contributed to the negative
      bias in DeltaVm asymmetry at sites polarized by physical and virtual electrodes,
      but also restricted positive DeltaVm. Inclusion of Ia and electroporation is thus
      the bridge between experiment and simulation.

PMID- 15454430
TI  - Phase resetting and phase locking in hybrid circuits of one model and one
      biological neuron.
AB  - To determine why elements of central pattern generators phase lock in a
      particular pattern under some conditions but not others, we tested a theoretical
      pattern prediction method. The method is based on the tabulated open loop
      pulsatile interactions of bursting neurons on a cycle-by-cycle basis and was
      tested in closed loop hybrid circuits composed of one bursting biological neuron
      and one bursting model neuron coupled using the dynamic clamp. A total of 164
      hybrid networks were formed by varying the synaptic conductances. The prediction
      of 1:1 phase locking agreed qualitatively with the experimental observations,
      except in three hybrid circuits in which 1:1 locking was predicted but not
      observed. Correct predictions sometimes required consideration of the second
      order phase resetting, which measures the change in the timing of the second
      burst after the perturbation. The method was robust to offsets between the
      initiation of bursting in the presynaptic neuron and the activation of the
      synaptic coupling with the postsynaptic neuron. The quantitative accuracy of the
      predictions fell within the variability (10%) in the experimentally observed
      intrinsic period and phase resetting curve (PRC), despite changes in the burst
      duration of the neurons between open and closed loop conditions.

PMID- 15454431
TI  - Ion permeation through the alpha-hemolysin channel: theoretical studies based on
      Brownian dynamics and Poisson-Nernst-Plank electrodiffusion theory.
AB  - Identification of the molecular interaction governing ion conduction through
      biological pores is one of the most important goals of modern electrophysiology.
      Grand canonical Monte Carlo Brownian dynamics (GCMC/BD) and three-dimensional
      Poisson-Nernst-Plank (3d-PNP) electrodiffusion algorithms offer powerful and
      general approaches to study of ion permeation through wide molecular pores. A
      detailed analysis of ion flows through the staphylococcal alpha-hemolysin channel
      based on series of simulations at different concentrations and transmembrane
      potentials is presented. The position-dependent diffusion coefficient is
      approximated on the basis of a hydrodynamic model. The channel conductance
      calculated by GCMC/BD is approximately 10% higher than (electrophysiologically
      measured) experimental values, whereas results from 3d-PNP are always 30-50%
      larger. Both methods are able to capture all important electrostatic interactions
      in equilibrium conditions. The asymmetric conductance upon the polarity of the
      transmembrane potential observed experimentally is reproduced by GCMC/BD and 3d
      PNP. The separation of geometrical and energetic influence of the channel on ion
      conduction reveals that such asymmetries arise from the permanent charge
      distribution inside the pore. The major determinant of the asymmetry is
      unbalanced charge in the triad of polar residues D127, D128, and K131. The
      GCMC/BD or 3d-PNP calculations reproduce also experimental reversal potentials
      and permeability rations in asymmetric ionic solutions. The weak anionic
      selectivity of the channel results from the presence of the salt bridge between
      E111 and K147 in the constriction zone. The calculations also reproduce the
      experimentally derived dependence of the reversible potential to the direction of
      the salt gradient. The origin of such effect arises from the asymmetrical
      distribution of energetic barriers along the channel axis, which modulates the
      preferential ion passage in different directions.

PMID- 15454432
TI  - Molecular dynamics simulation of amyloid beta dimer formation.
AB  - Recent experiments with amyloid beta (Abeta) peptide indicate that formation of
      toxic oligomers may be an important contribution to the onset of Alzheimer's
      disease. The toxicity of Abeta oligomers depends on their structure, which is
      governed by assembly dynamics. Due to limitations of current experimental
      techniques, a detailed knowledge of oligomer structure at the atomic level is
      missing. We introduce a molecular dynamics approach to study Abeta dimer
      formation. 1), We use discrete molecular dynamics simulations of a coarse-grained
      model to identify a variety of dimer conformations; and 2), we employ all-atom
      molecular mechanics simulations to estimate thermodynamic stability of all dimer
      conformations. Our simulations of a coarse-grained Abeta peptide model predicts
      10 different planar beta-strand dimer conformations. We then estimate the free
      energies of all dimer conformations in all-atom molecular mechanics simulations
      with explicit water. We compare the free energies of Abeta(1-42) and Abeta(1-40)
      dimers. We find that 1), dimer conformations have higher free energies compared
      to their corresponding monomeric states; and 2), the free-energy difference
      between the Abeta(1-42) and the corresponding Abeta(1-40) dimer conformation is
      not significant. Our results suggest that Abeta oligomerization is not
      accompanied by the formation of thermodynamically stable planar beta-strand
      dimers.

PMID- 15454433
TI  - Rheology and ultrasound scattering from aggregated red cell suspensions in shear
      flow.
AB  - The shear flow dynamics of reversible red cell aggregates in dense suspensions
      were investigated by ultrasound scattering, to study the shear disruption
      processes of Rayleigh clusters and examine the effective mean field approximation
      used in microrheological models. In a first section, a rheo-acoustical model, in
      the Rayleigh scattering regime, is proposed to describe the shear stress
      dependence of the low frequency scattered power in relation to structural
      parameters. The fractal scattering regime characterizing the anisotropic
      scattering from flocs of size larger than the ultrasound wavelength is further
      discussed. In the second section, we report flow-dependent changes in the low
      frequency scattering coefficient in a plane-plane flow geometry to analyze the
      shear disruption processes of hardened or deformable red cell aggregates in
      neutral dextran polymer solution. Rheo-acoustical experiments are examined on the
      basis of the rheo-acoustical model and the effective medium approximation. The
      ability of ultrasound scattering technique to determine the critical
      disaggregation shear stress and to give quantitative information on particle
      surface adhesive energy is analyzed. Lastly, the shear-thinning behavior of
      weakly aggregated hardened or deformable red cells is described.

PMID- 15454434
TI  - A model of the putative pore region of the cardiac ryanodine receptor channel.
AB  - Using the bacterial K+ channel KcsA as a template, we constructed models of the
      pore region of the cardiac ryanodine receptor channel (RyR2) monomer and
      tetramer. Physicochemical characteristics of the RyR2 model monomer were compared
      with the template, including homology, predicted secondary structure, surface
      area, hydrophobicity, and electrostatic potential. Values were comparable with
      those of KcsA. Monomers of the RyR2 model were minimized and assembled into a
      tetramer that was, in turn, minimized. The assembled tetramer adopts a structure
      equivalent to that of KcsA with a central pore. Characteristics of the RyR2 model
      tetramer were compared with the KcsA template, including average empirical
      energy, strain energy, solvation free energy, solvent accessibility, and
      hydrophobic, polar, acid, and base moments. Again, values for the model and
      template were comparable. The pores of KcsA and RyR2 have a common motif with a
      hydrophobic channel that becomes polar at both entrances. Quantitative
      comparisons indicate that the assembled structure provides a plausible model for
      the pore of RyR2. Movement of Ca2+, K+, and tetraethylammonium (TEA+) through the
      model RyR2 pore were simulated with explicit solvation. These simulations suggest
      that the model RyR2 pore is permeable to Ca2+ and K+ with rates of translocation
      greater for K+. In contrast, simulations indicate that tetraethylammonium blocks
      movement of metal cations.

PMID- 15454435
TI  - Consequences of molecular-level Ca2+ channel and synaptic vesicle colocalization
      for the Ca2+ microdomain and neurotransmitter exocytosis: a monte carlo study.
AB  - Morphological and biochemical studies indicate association between voltage-gated
      Ca2+ channels and the vesicle docking complex at vertebrate presynaptic active
      zones, which constrain the separation between some Ca2+ channels and vesicles to
      20 nm or less. To address the effect of the precise geometrical relationship
      among the vesicles, the Ca2+ channel, and the proteins of the release machinery
      on neurotransmitter release, we developed a Monte Carlo simulation of Ca2+
      diffusion and buffering with nanometer resolution. We find that the presence of a
      vesicle as a diffusion barrier alters the shape of the Ca2+ microdomain of a
      single Ca2+ channel around the vesicle. This effect is maximal in the vicinity of
      the vesicle and depends critically on the vesicle's distance from the
      plasmalemma. Ca2+-sensor(s) for release would be exposed to markedly different
      [Ca2+], varying by up to 13-fold, depending on their position around the vesicle.
      As a result, the precise position of Ca2+-sensor(s) with respect to the vesicle
      and the channel can be critical to determining the release probability. Variation
      in the position of Ca2+-sensor molecule(s) and their accessibility could be an
      important source of heterogeneity in vesicle release probability.

PMID- 15454436
TI  - Coupled motions between pore and voltage-sensor domains: a model for Shaker B, a
      voltage-gated potassium channel.
AB  - A high-resolution crystal structure of KvAP, an archeabacterial voltage-gated
      potassium (Kv) channel, complexed with a monoclonal Fab fragment has been
      recently determined. Based on this structure, a mechanism for the activation
      (opening) of Kv channels has been put forward. This mechanism has since been
      criticized, suggesting that the resolved structure is not representative of the
      family of voltage-gated potassium channels. Here, we propose a model of the
      transmembrane domain of Shaker B, a well-characterized Kv channel, built by
      homology modeling and docking calculations. In this model, the positively charged
      S4 helices are oriented perpendicular to the membrane and localized in the groove
      between segments S5 and S6 of adjacent subunits. The structure and the dynamics
      of the full atomistic model embedded in a hydrated lipid bilayer were
      investigated by means of two large-scale molecular dynamics simulations under
      transmembrane-voltage conditions known to induce, respectively, the resting state
      (closed) and the activation (opening) of voltage-gated channels. Upon activation,
      the model undergoes conformational changes that lead to an increase of the
      hydration of the charged S4 helices, correlated with an upward translation and a
      tilting of the latter, concurrently with movements of the S5 helices and the
      activation gate. Although small, these conformational changes ultimately result
      in an alteration of the ion-conduction pathway. Our findings support the
      transporter model devised by Bezanilla and collaborators, and further underline
      the crucial role played by internal hydration in the activation of the channel.

PMID- 15454437
TI  - Modulation of Kv4.2 channel expression and gating by dipeptidyl peptidase 10
      (DPP10).
AB  - The dipeptidyl aminopeptidase-like protein DPPX (DPP6) associates with Kv4
      potassium channels, increasing surface trafficking and reconstituting native
      neuronal ISA-like properties. Dipeptidyl peptidase 10 (DPP10) shares with DPP6 a
      high amino acid identity, lack of enzymatic activity, and expression
      predominantly in the brain. We used a two-electrode voltage-clamp and oocyte
      expression system to determine if DPP10 also interacts with Kv4 channels and
      modulates their expression and function. Kv4.2 coimmunoprecipitated with HA/DPP10
      from extracts of oocytes heterologously expressing both proteins. Coexpression
      with DPP10 and HA/DPP10 enhanced Kv4.2 current by approximately fivefold without
      increasing protein level. DPP10 also remodeled Kv4.2 kinetic and steady-state
      properties by accelerating time courses of inactivation and recovery (taurec: WT
      = 200 ms, +DPP10 = 78 ms). Furthermore, DPP10 introduced hyperpolarizing shifts
      in the conductance-voltage relationship (approximately 19 mV) as well as steady
      state inactivation (approximately 7 mV). The effects of DPP10 on Kv4.1 were
      similar to Kv4.2; however, distinct biophysical differences were observed.
      Additional experiments suggested that the cytoplasmic N-terminal domain of DPP10
      determines the acceleration of inactivation. In summary, DPP10 is a potent
      modulator of Kv4 expression and biophysical properties and may be a critical
      component of somatodendritic ISA channels in the brain.

PMID- 15454438
TI  - Exchange of gating properties between rat cx46 and chicken cx45.6.
AB  - Cx46 and Cx50 are coexpressed in lens fiber cells where they form fiber-fiber gap
      junctions. Recent studies have shown that both proteins play a critical role in
      maintaining lens transparency. Although both Cx46 and Cx50 (or its chicken
      ortholog, Cx45.6) show a high degree of sequence homology, they exhibit marked
      differences in gap junctional channel gating, unitary gap junctional channel
      conductance, and hemichannel gating. To better understand which regions of the
      protein are responsible for these functional differences, we have constructed a
      series of chimeric Cx46-Cx45.6 gap junctional proteins in which a single
      transmembrane or intracellular domain of Cx45.6 was replaced with the
      corresponding domain of Cx46, expressed them in Xenopus oocyte pairs or N2A
      cells, and examined the resulting gap junctional conductances. Our results showed
      that four out of six of the chimeras induced high levels of gap junctional
      coupling. Of these chimeras, only Cx45.6-46NT showed significant changes in
      voltage-dependent gating properties. Exchanging the N-terminus had multiple
      effects. It slowed the inactivation kinetics of the macroscopic junctional
      currents so that they resembled those of Cx46, reduced the voltage sensitivity of
      the steady-state junctional conductance, and decreased the conductance of single
      gap junctional channels. Additional point mutations identified a uniquely
      occurring arginine in the N-terminus of Cx46 as the main determinant for the
      change in voltage-dependent gating.

PMID- 15454439
TI  - K+ activation of kir3.1/kir3.4 and kv1.4 K+ channels is regulated by
      extracellular charges.
AB  - K+ activates many inward rectifier and voltage-gated K+ channels. In each case,
      an increase in K+ current through the channel can occur despite a reduced driving
      force. We have investigated the molecular mechanism of K+ activation of the
      inward rectifier K+ channel, Kir3.1/Kir3.4, and the voltage-gated K+ channel,
      Kv1.4. In the Kir3.1/Kir3.4 channel, mutation of an extracellular arginine
      residue, R155, in the Kir3.4 subunit markedly reduced K+ activation of the
      channel. The same mutation also abolished Mg2+ block of the channel. Mutation of
      the equivalent residue in Kv1.4 (K532) abolished K+ activation as well as C-type
      inactivation of the Kv1.4 channel. Thus, whereas C-type inactivation is a
      collapse of the selectivity filter, K+ activation could be an opening of the
      selectivity filter. K+ activation of the Kv1.4 channel was enhanced by acidic pH.
      Mutation of an extracellular histidine residue, H508, that mediates the
      inhibitory effect of protons on Kv1.4 current, abolished both K+ activation and
      the enhancement of K+ activation at acidic pH. These results suggest that the
      extracellular positive charges in both the Kir3.1/Kir3.4 and the Kv1.4 channels
      act as "guards" and regulate access of K+ to the selectivity filter and, thus,
      the open probability of the selectivity filter. Furthermore, these data suggest
      that, at acidic pH, protonation of H508 inhibits current through the Kv1.4
      channel by decreasing K+ access to the selectivity filter, thus favoring the
      collapse of the selectivity filter.

PMID- 15454440
TI  - Interaction of melittin with membrane cholesterol: a fluorescence approach.
AB  - We have monitored the organization and dynamics of the hemolytic peptide melittin
      in membranes containing cholesterol by utilizing the intrinsic fluorescence
      properties of its functionally important sole tryptophan residue and circular
      dichroism spectroscopy. The significance of this study is based on the fact that
      the natural target for melittin is the erythrocyte membrane, which contains high
      amounts of cholesterol. Our results show that the presence of cholesterol
      inhibits melittin-induced leakage of lipid vesicles and the extent of inhibition
      appears to be dependent on the concentration of membrane cholesterol. The
      presence of cholesterol is also shown to reduce binding of melittin to membranes.
      Our results show that fluorescence parameters such as intensity, emission
      maximum, and lifetime of membrane-bound melittin indicate a change in polarity in
      the immediate vicinity of the tryptophan residue probably due to increased water
      penetration in presence of cholesterol. This is supported by results from
      fluorescence quenching experiments using acrylamide as the quencher. Membrane
      penetration depth analysis by the parallax method shows that the melittin
      tryptophan is localized at a relatively shallow depth in membranes containing
      cholesterol. Analysis of energy transfer results using melittin tryptophan
      (donor) and dehydroergosterol (acceptor) indicates that dehydroergosterol is not
      randomly distributed and is preferentially localized around the tryptophan
      residue of membrane-bound melittin, even at the low concentrations used. Taken
      together, our results are relevant in understanding the interaction of melittin
      with membranes in general, and with cholesterol-containing membranes in
      particular, with possible relevance to its interaction with the erythrocyte
      membrane.

PMID- 15454441
TI  - The range and shielding of dipole-dipole interactions in phospholipid bilayers.
AB  - In molecular dynamics simulations of lipid bilayers, the structure is sensitive
      to the precise treatment of electrostatics. The dipole-dipole interactions
      between headgroup dipoles are not long-ranged, but the area per lipid and,
      through it, other properties of the bilayer are very sensitive to the detailed
      balance between the perpendicular and in-plane components of the headgroup
      dipoles. This is affected by the detailed properties of the cutoff scheme or if
      long-range interactions are included by Ewald or particle-mesh Ewald techniques.
      Interaction between the in-plane components of the headgroup dipoles is
      attractive and decays as the inverse sixth power of distance. The interaction is
      screened by the square of a dielectric permittivity close to the value for water.
      Interaction between the components perpendicular to the membrane plane is
      repulsive and decays as the inverse third power of distance. These interactions
      are screened by a dielectric permittivity of the order 10. Thus, despite the
      perpendicular components being much smaller in magnitude than the in-plane
      components, they will dominate the interaction energies at large distances.

PMID- 15454442
TI  - Using the atomic force microscope to study the interaction between two solid
      supported lipid bilayers and the influence of synapsin I.
AB  - To measure the interaction between two lipid bilayers with an atomic force
      microscope one solid supported bilayer was formed on a planar surface by
      spontaneous vesicle fusion. To spontaneously adsorb lipid bilayers also on the
      atomic force microscope tip, the tips were first coated with gold and a monolayer
      of mercapto undecanol. Calculations indicate that long-chain hydroxyl terminated
      alkyl thiols tend to enhance spontaneous vesicle fusion because of an increased
      van der Waals attraction as compared to short-chain thiols. Interactions measured
      between dioleoylphosphatidylcholine, dioleoylphosphatidylserine, and
      dioleoyloxypropyl trimethylammonium chloride showed the electrostatic double
      layer force plus a shorter-range repulsion which decayed exponentially with a
      decay length of 0.7 nm for dioleoylphosphatidylcholine, 1.2 nm for
      dioleoylphosphatidylserine, and 0.8 nm for dioleoyloxypropyl trimethylammonium
      chloride. The salt concentration drastically changed the interaction between
      dioleoyloxypropyl trimethylammonium chloride bilayers. As an example for the
      influence of proteins on bilayer-bilayer interaction, the influence of the
      synaptic vesicle-associated, phospholipid binding protein synapsin I was studied.
      Synapsin I increased membrane stability so that the bilayers could not be
      penetrated with the tip.

PMID- 15454443
TI  - Anomalous diffusion in a gel-fluid lipid environment: a combined solid-state NMR
      and obstructed random-walk perspective.
AB  - Lateral diffusion is an essential process for the functioning of biological
      membranes. Solid-state nuclear magnetic resonance (NMR) is, a priori, a well
      suited technique to study lateral diffusion within a heterogeneous environment
      such as the cell membrane. Moreover, restriction of lateral motions by lateral
      heterogeneities can be used as a means to characterize their geometry. The goal
      of this work is to understand the advantages and limitations of solid-state NMR
      exchange experiments in the study of obstructed lateral diffusion in model
      membranes. For this purpose, simulations of lateral diffusion on a sphere with
      varying numbers and sizes of immobile obstacles and different percolation
      properties were performed. From the results of these simulations, two-dimensional
      31P NMR exchange maps and time-dependent autocorrelation functions were
      calculated. The results indicate that the technique is highly sensitive to
      percolation properties, total obstacle area, and, within certain limits, obstacle
      size. A practical example is shown, namely the study of the well-characterized
      DMPC-DSPC binary mixture. The comparison of experimental and simulated results
      yielded obstacle sizes in the range of hundreds of nanometers, therefore bridging
      the gap between previously published NMR and fluorescence recovery after
      photobleaching results. The method could also be applied to the study of membrane
      protein lateral diffusion in model membranes.

PMID- 15454444
TI  - Effect of variations in the structure of a polyleucine-based alpha-helical
      transmembrane peptide on its interaction with phosphatidylethanolamine Bilayers.
AB  - High-sensitivity differential scanning calorimetry and Fourier transform infrared
      spectroscopy were used to study the interaction of a cationic alpha-helical
      transmembrane peptide, acetyl-Lys2-Leu24-Lys2-amide (L24), and members of the
      homologous series of zwitterionic n-saturated diacyl phosphatidylethanolamines
      (PEs). Analogs of L24, in which the lysine residues were replaced by 2,3
      diaminopropionic acid (acetyl-DAP2-Leu24-DAP2-amide (L24DAP)) or in which a
      leucine residue at each end of the polyleucine sequence was replaced by a
      tryptophan (Ac-K2-W-L22-W-K2-amide (WL22W)), were also studied to investigate the
      roles of lysine side-chain snorkeling and aromatic side-chain interactions with
      the interfacial region of phospholipid bilayers. The gel/liquid-crystalline phase
      transition temperature of the PE bilayers is altered by these peptides in a
      hydrophobic mismatch-independent manner, in contrast to the hydrophobic mismatch
      dependent manner observed previously with zwitterionic phosphatidylcholine (PC)
      and anionic phosphatidylglycerol (PG) bilayers. Moreover, all three peptides
      reduce the phase transition temperature to a greater extent in PE bilayers than
      in PC and PG bilayers, indicating a greater disruption of PE gel-phase bilayer
      organization. Moreover, the lysine-anchored L24 reduces the phase transition
      temperature, enthalpy, and the cooperativity of PE bilayers to a much greater
      extent than DAP-anchored L24DAP, whereas replacement of the terminal leucines by
      tryptophan residues (Ac-K2-W-L22-W-K2-amide) only slightly attenuates the effects
      of this peptide on the chain-melting phase transition of the host PE bilayers.
      All three peptides form very stable alpha-helices in PE bilayers, but small
      conformational changes occur in response to mismatch between peptide hydrophobic
      length and gel-state lipid bilayer hydrophobic thickness. These results suggest
      that the lysine snorkeling plays a significant role in the peptide-PE
      interactions and that cation-pi-interactions between lysine and tryptophan
      residues may modulate these interactions. Altogether, these results suggest that
      the lipid-peptide interactions are affected not only by the hydrophobic mismatch
      between these peptides and the host lipid bilayer but also by the electrostatic
      and hydrogen-bonding interactions between the positively charged lysine residues
      at the termini of these peptides and the polar headgroups of PE bilayers.

PMID- 15454445
TI  - Dynamic molecular structure of DPPC-DLPC-cholesterol ternary lipid system by spin
      label electron spin resonance.
AB  - The hydrated ternary lamellar lipid mixture of dipalmitoyl-PC/dilauroyl
      PC/cholesterol (DPPC/DLPC/Chol) has been studied by electron spin resonance (ESR)
      to reveal the dynamic structure on a molecular level of the different phases that
      exist and coexist over virtually the full range of composition. The spectra for
      more than 100 different compositions at room temperature were analyzed by
      nonlinear least-squares fitting to provide the rotational diffusion rates and
      order parameters of the end-chain labeled phospholipid 16-PC. The ESR spectra
      exhibit substantial variation as a function of composition, even though the
      respective phases generally differ rather modestly from each other. The Lalpha
      and Lbeta phases are clearly distinguished, with the former exhibiting
      substantially lower ordering and greater motional rates, whereas the well-defined
      Lo phase exhibits the greatest ordering and relatively fast motional rates.
      Typically, smaller variations occur within a given phase. The ESR spectral
      analysis also yields phase boundaries and coexistence regions which are found to
      be consistent with previous results from fluorescence methods, although new
      features are found. Phase coexistence regions were in some cases confirmed by
      observing the existence of isosbestic points in the absorption mode ESR spectra
      from the phases. The dynamic structural properties of the DPPC-rich Lbeta and
      DLPC-rich Lalpha phases, within their two-phase coexistence region do not change
      with composition along a tie-line, but the ratio of the two phases follows the
      lever rule in accordance with thermodynamic principles. The analysis shows that
      16-PC spin-label partitions nearly equally between the Lalpha and Lbeta phases,
      making it a useful probe for studying such coexisting phases. Extensive study of
      two-phase coexistence regions requires the determination of tie-lines, which were
      approximated in this study. However, a method is suggested to accurately
      determine the tie-lines by ESR.

PMID- 15454446
TI  - Stalk phase formation: effects of dehydration and saddle splay modulus.
AB  - One of the earliest lipid intermediates forming in the course of membrane fusion
      is the lipid stalk. Although many aspects of the stalk hypothesis were elaborated
      theoretically and confirmed by experiments it remained unresolved whether stalk
      formation is always an energy consuming process or if there are conditions where
      the stalks are energetically favorable and form spontaneously resulting in an
      equilibrium stalk phase. Motivated by a recent breakthrough experiments we
      analyze the physical factors determining the spontaneous stalk formation. We show
      that this process can be driven by interplay between two factors: the elastic
      energy of lipid monolayers including a contribution of the saddle splay
      deformation and the energy of hydration repulsion acting between apposing
      membranes. We analyze the dependence of stalk formation on the saddle splay
      (Gaussian) modulus of the lipid monolayers and estimate the values of this
      modulus based on the experimentally established phase boundary between the
      lamellar and the stalk phases. We suggest that fusion proteins can induce stalk
      formation just by bringing the membranes into close contact, and accumulating, at
      least locally, a sufficiently large energy of the hydration repulsion.

PMID- 15454447
TI  - Structural calorimetry of main transition of supported DMPC bilayers by
      temperature-controlled AFM.
AB  - Atomic force microscopy at high temperature resolution (DeltaT < or approximately
      0.1 K) provided a quantitative structural calorimetry of the transition from the
      fluid (Lalpha)- to the gel (Pbeta')-phase of supported
      dimyristoylphosphatidylcholine bilayers. Besides a determination of the main
      transition temperature (T0) and the van't Hoff transition enthalpy (DeltaHvH),
      the structural analysis in the nm-scale at T close to T0 of the ripple phase
      allowed an experimental estimation of the area of cooperative units from small
      lipid domains. Thereby, the corresponding transition enthalpy (DeltaH) of single
      molecules could be determined. The lipid organization and the corresponding
      parameters T0 and DeltaHvH (DeltaH) were modulated by heptanol or external Ca2+
      and compared with physiological findings. The size of the cooperative unit was
      not significantly affected by the presence of 1 mM heptanol. The observed linear
      relationship of DeltaHvH and T0 was discussed in terms of a change in heat
      capacity.

PMID- 15454448
TI  - The force exerted by a muscle cross-bridge depends directly on the strength of
      the actomyosin bond.
AB  - Myosin produces force in a cyclic interaction, which involves alternate tight
      binding to actin and to ATP. We have investigated the energetics associated with
      force production by measuring the force generated by skinned muscle fibers as the
      strength of the actomyosin bond is changed. We varied the strength of the
      actomyosin bond by addition of a polymer that promotes protein-protein
      association or by changing temperature or ionic strength. We estimated the free
      energy available to generate force by measuring isometric tension, as the free
      energy of the states that precede the working stroke are lowered with increasing
      phosphate. We found that the free energy available to generate force and the
      force per attached cross-bridge at low [Pi] were both proportional to the free
      energy available from the formation of the actomyosin bond. We conclude that the
      formation of the actomyosin bond is involved in providing the free energy driving
      the production of isometric tension and mechanical work. Because the binding of
      myosin to actin is an endothermic, entropically driven reaction, work must be
      performed by a "thermal ratchet" in which a thermal fluctuation in Brownian
      motion is captured by formation of the actomyosin bond.

PMID- 15454449
TI  - Sequence-dependence of the energetics of opening of at basepairs in DNA.
AB  - Proton exchange and nuclear magnetic resonance spectroscopy are being used to
      characterize the energetics of opening of AT/TA basepairs in the DNA dodecamer 5'
      d(GCTATAAAAGGG)-3'/5'-d(CCCTTTTATAGC)-3'. The dodecamer contains the TATA box of
      the adenovirus major late promoter. The equilibrium constants for opening of each
      basepair are measured from the dependence of the exchange rates of imino protons
      on ammonia concentration. The enthalpy, entropy, and free energy changes in the
      opening reaction of each basepair are determined from the temperature dependence
      of the exchange rates. The results reveal that the opening enthalpy changes
      encompass a wide range of values, namely, from 17 to 29 kcal/mol. The largest
      values are observed for the AT basepairs in 7th and 8th positions. These values,
      and the exchange rates of the corresponding imino protons, suggest that these two
      basepairs open in a single concerted reaction. The enthalpy changes for opening
      of the central six basepairs are correlated to the opening entropy changes. This
      enthalpy-entropy compensation minimizes the variations in the opening free
      energies among these central basepairs. Deviations from the enthalpy-entropy
      compensation pattern are observed for basepairs located close to the ends of the
      duplex structure, suggesting a different mode of opening for these basepairs.

PMID- 15454450
TI  - Twisting and untwisting a single DNA molecule covered by RecA protein.
AB  - We study dsDNA-RecA interactions by exerting forces in the pN range on single DNA
      molecules while the interstrand topological state is controlled owing to a
      magnetic tweezers setup. We show that unwinding a duplex DNA molecule induces
      RecA polymerization even at moderate force. Once initial polymerization has
      nucleated, the extent of RecA coverage still depends on the degree of
      supercoiling: exerting a positive or negative torsional constraint on the fiber
      forces partial depolymerization, with a strikingly greater stability when
      ATPgammaS is used as a cofactor instead of ATP. This nucleofilament's sensitivity
      to topology might be a way for the bacterial cell to limit consumption of
      precious RecA monomers when DNA damage is addressed through homologous
      recombination repair.

PMID- 15454451
TI  - Differences between EcoRI nonspecific and "star" sequence complexes revealed by
      osmotic stress.
AB  - The binding of the restriction endonuclease EcoRI to DNA is exceptionally
      specific. Even a single basepair change ("star" sequence) from the recognition
      sequence, GAATTC, decreases the binding free energy of EcoRI to values nearly
      indistinguishable from nonspecific binding. The difference in the number of
      waters sequestered by the protein-DNA complexes of the "star" sequences TAATTC
      and CAATTC and by the specific sequence complex determined from the dependence of
      binding free energy on water activity is also practically indistinguishable at
      low osmotic pressures from the 110 water molecules sequestered by nonspecific
      sequence complexes. Novel measurements of the dissociation rates of noncognate
      sequence complexes and competition equilibrium show that sequestered water can be
      removed from "star" sequence complexes by high osmotic pressure, but not from a
      nonspecific complex. By 5 Osm, the TAATTC "star" sequence complex has lost almost
      90 of the approximately 110 waters initially present. It is more difficult to
      remove water from the CAATTC "star" sequence complex. The sequence dependence of
      water loss correlates with the known sequence dependence of "star" cleavage
      activity.

PMID- 15454452
TI  - Evidence for a novel mechanism of time-resolved flavin fluorescence
      depolarization in glutathione reductase.
AB  - Time-resolved flavin fluorescence anisotropy studies on glutathione reductase
      (GR) have revealed a remarkable new phenomenon: wild-type GR displays a rapid
      process of fluorescence depolarization, that is absent in mutant enzymes lacking
      a nearby tyrosine residue that blocks the NADPH-binding cleft. Fluorescence
      lifetime data, however, have shown a more rigid active-site structure for wild
      type GR than for the tyrosine mutants. These results suggest that the rapid
      depolarization in wild-type GR originates from an interaction with the flavin
      shielding tyrosine, and not from restricted reorientational motion of the flavin.
      A novel mechanism of fluorescence depolarization is proposed that involves a
      transient charge-transfer complex between the tyrosine and the light-excited
      flavin, with a concomitant change in the direction of the emission dipole moment
      of the flavin. This interaction is likely to result from side-chain relaxation of
      the tyrosine in the minor fraction of enzyme molecules in which this residue is
      in an unsuitable position for immediate fluorescence quenching at the moment of
      excitation. Support for this mechanism is provided by binding studies with NADP+
      and 2'P-5'ADP-ribose that can intercalate between the flavin and tyrosine and/or
      block the latter. Fluorescence depolarization analyses as a function of
      temperature and viscosity confirm the dynamic nature of the process. A comparison
      with fluorescence depolarization effects in a related flavoenzyme indicates that
      this mechanism of flavin fluorescence depolarization is more generally
      applicable.

PMID- 15454453
TI  - Time-resolved detection of sensory rhodopsin II-transducer interaction.
AB  - The dynamics of protein conformational change of Natronobacterium pharaonis
      sensory rhodopsin II (NpSRII) and of NpSRII fused to cognate transducer (NpHtrII)
      truncated at 159 amino acid sequence from the N-terminus (NpSRII-DeltaNpHtrII)
      are investigated in solution phase at room temperature by the laser flash
      photolysis and the transient grating methods in real time. The diffusion
      coefficients of both species indicate that the NpSRII-DeltaNpHtrII exists in the
      dimeric form in 0.6% dodecyl-beta-maltopyranoside (DM) solution. Rate constants
      of the reaction processes in the photocycles determined by the transient
      absorption and grating methods agree quite well. Significant differences were
      found in the volume change and the molecular energy between NpSRII and NpSRII
      DeltaNpHtrII samples. The enthalpy of the second intermediate (L) of NpSRII
      DeltaNpHtrII is more stabilized compared with that of NpSRII. This stabilization
      indicates the influence of the transducer to the NpSRII structure in the early
      intermediate species by the complex formation. Relatively large molecular volume
      expansion and contraction were observed in the last two steps for NpSRII.
      Additional volume expansion and contraction were induced by the presence of
      DeltaNpHtrII. This volume change, which should reflect the conformational change
      induced by the transducer protein, suggested that this is the signal transduction
      process of the NpSRII-DeltaNpHtrII.

PMID- 15454454
TI  - Single-molecule spectroscopy selectively probes donor and acceptor chromophores
      in the phycobiliprotein allophycocyanin.
AB  - We report on single-molecule fluorescence measurements performed on the
      phycobiliprotein allophycocyanin (APC). Our data support the presence of a
      unidirectional Forster-type energy transfer process involving spectrally
      different chromophores, alpha84 (donor) and beta84 (acceptor), as well as of
      energy hopping amongst beta84 chromophores. Single-molecule fluorescence spectra
      recorded from individual immobilized APC proteins indicate the presence of a red
      emitting chromophore with emission peaking at 660 nm, which we connect with
      beta84, and a species with the emission peak blue shifted at 630 nm, which we
      attribute to alpha84. Polarization data from single APC trimers point to the
      presence of three consecutive red emitters, suggesting energy hopping amongst
      beta84 chromophores. Based on the single-molecule fluorescence spectra and
      assuming that emission at the ensemble level in solution comes mainly from the
      acceptor chromophore, we were able to resolve the individual absorption and
      emission spectra of the alpha84 and beta84 chromophores in APC.

PMID- 15454455
TI  - Unfolding of ubiquitin studied by picosecond time-resolved fluorescence of the
      tyrosine residue.
AB  - The photophysics of the single tyrosine in bovine ubiquitin (UBQ) was studied by
      picosecond time-resolved fluorescence spectroscopy, as a function of pH and along
      thermal and chemical unfolding, with the following results: First, at room
      temperature (25 degrees C) and below pH 1.5, native UBQ shows single-exponential
      decays. From pH 2 to 7, triple-exponential decays were observed and the three
      decay times were attributed to the presence of tyrosine, a tyrosine-carboxylate
      hydrogen-bonded complex, and excited-state tyrosinate. Second, at pH 1.5, the
      water-exposed tyrosine of either thermally or chemically unfolded UBQ decays as a
      sum of two exponentials. The double-exponential decays were interpreted and
      analyzed in terms of excited-state intramolecular electron transfer from the
      phenol to the amide moiety, occurring in one of the three rotamers of tyrosine in
      UBQ. The values of the rate constants indicate the presence of different unfolded
      states and an increase in the mobility of the tyrosine residue during unfolding.
      Finally, from the pre-exponential coefficients of the fluorescence decays, the
      unfolding equilibrium constants (KU) were calculated, as a function of
      temperature or denaturant concentration. Despite the presence of different
      unfolded states, both thermal and chemical unfolding data of UBQ could be fitted
      to a two-state model. The thermodynamic parameters Tm = 54.6 degrees C, DeltaHTm
      = 56.5 kcal/mol, and DeltaCp = 890 cal/mol//K, were determined from the unfolding
      equilibrium constants calculated accordingly, and compared to values obtained by
      differential scanning calorimetry also under the assumption of a two-state
      transition, Tm = 57.0 degrees C, DeltaHm= 51.4 kcal/mol, and DeltaCp = 730
      cal/mol//K.

PMID- 15454456
TI  - Crystallization mechanisms of hemoglobin C in the R state.
AB  - Crystallization of the mutated hemoglobin, HbC, which occurs inside red blood
      cells of patients expressing betaC-globin and exhibiting the homozygous CC and
      the heterozygous SC (in which two mutant beta-globins, S and C, are expressed)
      diseases, is a convenient model for processes underlying numerous condensation
      diseases. As a first step, we investigated the molecular-level mechanisms of
      crystallization of this protein from high-concentration phosphate buffer in its
      stable carbomonoxy form using high-resolution atomic force microscopy. We found
      that in conditions of equilibrium with the solution, the crystals' surface
      reconstructs into four-molecule-wide strands along the crystallographic a (or b)
      axis. However, the crystals do not grow by the alignment of such preformed
      strands. We found that the crystals grow by the attachment of single molecules to
      suitable sites on the surface. These sites are located along the edges of new
      layers generated by two-dimensional nucleation or by screw dislocations. During
      growth, the steps propagate with random velocities, with the mean being an
      increasing function of the crystallization driving force. These results show that
      the crystallization mechanisms of HbC are similar to those found for other
      proteins. Therefore, strategies developed to control protein crystallization in
      vitro may be applicable to pathology-related crystallization systems.

PMID- 15454457
TI  - Direct discrimination between models of protein activation by single-molecule
      force measurements.
AB  - The limitations imposed on the analyses of complex chemical and biological
      systems by ensemble averaging can be overcome by single-molecule experiments.
      Here, we used a single-molecule technique to discriminate between two generally
      accepted mechanisms of a key biological process--the activation of proteins by
      molecular effectors. The two mechanisms, namely induced-fit and population-shift,
      are normally difficult to discriminate by ensemble approaches. As a model, we
      focused on the interaction between the nuclear transport effector, RanBP1, and
      two related complexes consisting of the nuclear import receptor, importin beta,
      and the GDP- or GppNHp-bound forms of the small GTPase, Ran. We found that
      recognition by the effector proceeds through either an induced-fit or a
      population-shift mechanism, depending on the substrate, and that the two
      mechanisms can be differentiated by the data.

PMID- 15454458
TI  - Correct diffusion coefficients of proteins in fluorescence correlation
      spectroscopy. Application to tubulin oligomers induced by Mg2+ and Paclitaxel.
AB  - In view of recent warnings for artifacts in fluorescence correlation
      spectroscopy, the diffusion coefficient of a series of labeled proteins in a wide
      range of molecular mass (43-670 kD) was determined and shown to be correct with
      respect to published values and the theory. Fluorescence correlation spectroscopy
      was then applied to the study of fluorescently labeled tubulin and its
      oligomerization in vitro induced by Mg2+ ions, paclitaxel, and a fluorescent
      derivative of paclitaxel (Flutax2). By applying relations derived from the theory
      of Oosawa, we were able to determine the association constant of the oligomers
      induced by Mg2+. With Flutax2 our experiments show that at nanomolar
      concentration, the fluorescent derivative is able to recruit tubulin dimers and
      to form oligomers of defined size. Flutax2 does not bind to microtubules
      preformed with paclitaxel, but it becomes preferentially incorporated into
      microtubules when Flutax2 oligomers are preformed, and microtubule formation is
      induced by paclitaxel addition. This shows that their incorporation into
      microtubules is faster than the displacement of the prebound drug. Experiments
      using fluorescently labeled tubulin and (unlabeled) paclitaxel confirm the
      induction of tubulin oligomers at limiting paclitaxel concentrations.

PMID- 15454459
TI  - Tertiary structure predictions on a comprehensive benchmark of medium to large
      size proteins.
AB  - We evaluate tertiary structure predictions on medium to large size proteins by
      TASSER, a new algorithm that assembles protein structures through rearranging the
      rigid fragments from threading templates guided by a reduced Calpha and side
      chain based potential consistent with threading based tertiary restraints.
      Predictions were generated for 745 proteins 201-300 residues in length that cover
      the Protein Data Bank (PDB) at the level of 35% sequence identity. With
      homologous proteins excluded, in 365 cases, the templates identified by our
      threading program, PROSPECTOR_3, have a root-mean-square deviation (RMSD) to
      native < 6.5 angstroms, with >70% alignment coverage. After TASSER assembly, in
      408 cases the best of the top five full-length models has a RMSD < 6.5 angstroms.
      Among the 745 targets are 18 membrane proteins, with one-third having a predicted
      RMSD < 5.5 A. For all representative proteins less than or equal to 300 residues
      that have corresponding multiple NMR structures in the Protein Data Bank,
      approximately 20% of the models generated by TASSER are closer to the NMR
      structure centroid than the farthest individual NMR model. These results suggest
      that reasonable structure predictions for nonhomologous large size proteins can
      be automatically generated on a proteomic scale, and the application of this
      approach to structural as well as functional genomics represent promising
      applications of TASSER.

PMID- 15454460
TI  - Protein stiffening and entropic stabilization in the subdenaturing limit of
      guanidine hydrochloride.
AB  - Subdenaturing concentrations of guanidine hydrochloride (GdnHCl) stabilize
      proteins. For ferrocytochrome c the stabilization is detected at subglobal level
      with no measured change in global stability. These deductions are made by
      comparing observed rates of thermally driven ferrocytochrome cHCO reactions with
      global unfolding rates of ferrocytochrome c measured by stopped flow and NMR
      hydrogen exchange in the presence of a wide range of GdnHCl concentrations at pH
      7, 22 degrees C.

PMID- 15454461
TI  - Kinetics of intermolecular interaction during protein folding of reduced
      cytochrome c.
AB  - Kinetics of intermolecular interaction between reduced cytochrome c (Cyt c)
      protein and solvent during the protein-refolding process is studied by monitoring
      the time dependence of apparent diffusion coefficient (D) using the pulsed-laser
      induced transient grating technique. The refolding was triggered by photoinduced
      reduction of unfolded Fe(III) Cyt c in 3.5 M guanidine hydrochloride (GdnHCl)
      solution and the change in the diffusion coefficient was monitored in time
      domain. The relationship between D and the protein conformations under
      equilibrium condition were investigated at various GdnHCl concentrations using a
      photolabeling reagent. The time dependence of the observed transient grating
      signal was analyzed using these data and two models: a continuous change model of
      the intermolecular interaction and a two-state model. It was found that the TG
      signals in various time ranges can be consistently reproduced well by the two
      state model. The dynamics of D is expressed well by a single exponential function
      with a rate constant of 22 +/- 7 s(-1) in a whole time range. The folding process
      of Cyt c is discussed based on these observations.

PMID- 15454462
TI  - LexA-DNA bond strength by single molecule force spectroscopy.
AB  - The SOS system of Escherichia coli is coordinated by two proteins: LexA, a
      repressor protein of several unlinked genes, and the coprotease RecA. As known to
      date LexA controls 31 genes with slightly different DNA binding motifs allowing
      for a variable degree of repression from one gene to the other. Besides the SOS
      system LexA plays an important role in the regulation of transcription. The
      protein regulates transcription by using particular motifs to bind DNA, the helix
      turn-helix motif. Here, we employed AFM-based single molecule force spectroscopy
      to characterize the interaction of LexA protein with two different DNA motifs:
      recA and yebG. We measured the dissociation rates to be 0.045 s(-1) for recA and
      0.13 s(-1) for yebG, respectively, which is in accordance with the predicted
      higher affinity between LexA-recA compared to LexA-yebG. The widths of the
      binding potentials were determined to be 5.4 +/- 1 angstroms and 4.9 +/- 0.5
      angstroms, respectively. This short-ranged potential is characteristic for a
      stiff hydrogen-bonding network between protein and DNA. The unbinding occurs in a
      breakup rather than a gradual sliding.

PMID- 15454463
TI  - Atomic model of the Thermus thermophilus 70S ribosome developed in silico.
AB  - The ribosome is a large molecular complex that consists of at least three
      ribonucleic acid molecules and a large number of proteins. It translates genetic
      information from messenger ribonucleic acid and makes protein accordingly. To
      better understand ribosomal function and provide information for designing
      biochemical experiments require knowledge of the complete structure of the
      ribosome. For expanding the structural information of the ribosome, we took on
      the challenge of developing a detailed Thermus thermophilus ribosomal structure
      computationally. By combining information derived from the low-resolution x-ray
      structure of the 70S ribosome (providing the overall fold), high-resolution
      structures of the ribosomal subunits (providing the local structure), sequences,
      and secondary structures, we have developed an atomic model of the T.
      thermophilus ribosome using a homology modeling approach. Our model is
      stereochemically sound with a consistent single-species sequence. The overall
      folds of the three ribosomal ribonucleic acids in our model are consistent with
      those in the low-resolution crystal structure (root mean-square differences are
      all <1.9 angstroms). The large overall interface area (approximately 2500
      angstroms2) of intersubunit bridges B2a, B3, and B5, and the inherent flexibility
      in regions connecting the contact residues are consistent with these bridges
      serving as anchoring patches for the ratcheting and rolling motions between the
      two subunits during translocation.

PMID- 15454464
TI  - A bending mode analysis for growing microtubules: evidence for a velocity
      dependent rigidity.
AB  - Microtubules are dynamic protein polymers that continuously switch between
      elongation and rapid shrinkage. They have an exceptional bending stiffness that
      contributes significantly to the mechanical properties of eukaryotic cells.
      Measurements of the persistence length of microtubules have been published since
      10 years but the reported values vary over an order of magnitude without an
      available explanation. To precisely measure the rigidity of microtubules in their
      native growing state, we adapted a previously developed bending mode analysis of
      thermally driven shape fluctuations to the case of an elongating filament that is
      clamped at one end. Microtubule shapes were quantified using automated image
      processing, allowing for the characterization of up to five bending modes. When
      taken together with three other less precise measurements, our rigidity data
      suggest that fast-growing microtubules are less stiff than slow-growing
      microtubules. This would imply that care should be taken in interpreting rigidity
      measurements on stabilized microtubules whose growth history is not known. In
      addition, time analysis of bending modes showed that higher order modes relax
      more slowly than expected from simple hydrodynamics, possibly by the effects of
      internal friction within the microtubule.

PMID- 15454465
TI  - Birth and growth kinetics of brome mosaic virus microcrystals.
AB  - The early steps of crystal nucleation and growth in Brome Mosaic virus and
      polyethylene glycol mixtures were analyzed using time-resolved x-ray scattering
      (at the European Synchrotron Radiation Facility, Grenoble, France). The system
      was chosen as a crystallization model since the phase diagram of the
      macromolecule/polymer mixture was known to present, at high polymer
      concentration, a solid, precipitated phase made of the synchronized formation of
      a large number of microcrystals. The precipitation and crystallization of the
      samples was induced by the controlled mixing of virus and polymer using a stopped
      flow device. Appearance and growth of Bragg diffraction peaks were used to follow
      the crystal nucleation and growth as a function of time, virus and polymer
      concentration, and polymer size. In all samples, the crystallization starts after
      a few seconds and proceeds for approximately 1-20 min until there is almost no
      virus left in the solution. The crystalline system was found to be face-centered
      cubic, with a unit cell size of 391 angstroms. The data analysis allowed us to
      show the presence of viruses in only two states, in solution or in crystals,
      revealing that the formation of periodic order proceeds without any detectable
      intermediate amorphous state.

PMID- 15454466
TI  - Using single-particle tracking to study nuclear trafficking of viral genes.
AB  - The question of how genetic materials are trafficked in and out of the cell
      nucleus is a problem of great importance not only for understanding viral
      infections but also for advancing gene-delivery technology. Here we demonstrate a
      physical technique that allows gene trafficking to be studied at the single-gene
      level by combining sensitive fluorescence microscopy with microinjection. As a
      model system, we investigate the nuclear import of influenza genes, in the form
      of ribonucleoproteins (vRNPs), by imaging single vRNPs in living cells in real
      time. Our single-particle trajectories show that vRNPs are transported to the
      nuclear envelope by diffusion. We have observed heterogeneous interactions
      between the vRNPs and nuclear pore complexes with dissociation rate constants
      spanning two orders of magnitude. Our single-particle tracking experiments also
      provided new insights into the regulation mechanisms for the nuclear import of
      vRNPs: the influenza M1 protein, a regulatory protein for the import process,
      downregulates the nuclear import of vRNPs by inhibiting the interactions between
      vRNPs and nuclear pore complexes but has no significant effect on the transport
      properties of vRNPs. We expect this single-particle tracking approach to find
      broad application in investigations of genetic trafficking.

PMID- 15454467
TI  - Secondary structure and secondary structure dynamics of DNA hairpins complexed
      with HIV-1 NC protein.
AB  - Reverse transcription of the HIV-1 RNA genome involves several complex nucleic
      acid rearrangement steps that are catalyzed by the HIV-1 nucleocapsid protein
      (NC), including for example, the annealing of the transactivation response (TAR)
      region of the viral RNA to the complementary region (TAR DNA) in minus-strand
      strong-stop DNA. We report herein single-molecule fluorescence resonance energy
      transfer measurements on single immobilized TAR DNA hairpins and hairpin mutants
      complexed with NC (i.e., TAR DNA/NC). Using this approach we have explored the
      conformational distribution and dynamics of the hairpins in the presence and
      absence of NC protein. The data demonstrate that NC shifts the equilibrium
      secondary structure of TAR DNA hairpins from a fully "closed" conformation to
      essentially one specific "partially open" conformation. In this specific
      conformation, the two terminal stems are "open" or unwound and the other stems
      are closed. This partially open conformation is arguably a key TAR DNA
      intermediate in the NC-induced annealing mechanism of TAR DNA.

PMID- 15454468
TI  - Evidence and implications of inhomogeneity in tectorial membrane elasticity.
AB  - The motion of the tectorial membrane (TM) with respect to the reticular lamina
      subserves auditory function by bending the outer hair cell bundles and inducing
      fluid flows that shear the inner hair bundles in response to sound energy. Little
      is currently known about its intrinsic elasticity or about the relation between
      the mechanical properties and function of the membrane. Here we subdivide the TM
      into three longitudinal regions and five radial zones and map the shear modulus
      of the TM using atomic force microscopy, and present evidence that the TM
      elasticity varies radially, after the distribution of type A collagen fibrils.
      This is seen most dramatically as a decrease in shear modulus in the neighborhood
      of the sensory hair cells; we argue that this inhomogeneity of properties not
      only protects the hair bundles but also increases the energy efficiency of the
      vibrational shearing during sound transduction.

PMID- 15454469
TI  - Imaging coronary artery microstructure using second-harmonic and two-photon
      fluorescence microscopy.
AB  - The microstructural basis for the mechanical properties of blood vessels has not
      been directly determined because of the lack of a nondestructive method that
      yields a three-dimensional view of these vascular wall constituents. Here, we
      demonstrate that multiphoton microscopy can be used to visualize the
      microstructural basis of blood vessel mechanical properties, by combining
      mechanical testing (distension) of excised porcine coronary arteries with
      simultaneous two-photon excited fluorescence and second-harmonic generation
      microscopy. Our results show that second-harmonic generation signals derived from
      collagen can be spectrally isolated from elastin and smooth muscle cell two
      photon fluorescence. Two-photon fluorescence signals can be further characterized
      by emission maxima at 495 nm and 520 nm, corresponding to elastin and cellular
      contributions, respectively. Two-dimensional reconstructions of spectrally fused
      images permit high-resolution visualization of collagen and elastin fibrils and
      smooth muscle cells from intima to adventitia. These structural features are
      confirmed by coregistration of multiphoton microscopy images with conventional
      histology. Significant changes in mean fibril thickness and overall wall
      dimension were observed when comparing no load (zero transmural pressure) and
      zero-stress conditions to 30 and 180 mmHg distension pressures. Overall, these
      data suggest that multiphoton microscopy is a highly sensitive and promising
      technique for studying the morphometric properties of the microstructure of the
      blood vessel wall.

PMID- 15454470
TI  - Polarized fluorescence resonance energy transfer microscopy.
AB  - Current methods for fluorescence resonance energy transfer (FRET) microscopy of
      living cells involve taking a series of images with alternating excitation colors
      in separate camera exposures. Here we present a new FRET method based on
      polarization that requires only one camera exposure and thereby offers the
      possibility for better time resolution of dynamic associations among subcellular
      components. Polarized FRET (p-FRET) uses a simultaneous combination of excitation
      wavelengths from two orthogonally polarized sources, along with an emission
      channel tri-image splitter outfitted with appropriate polarizers, to concurrently
      excite and collect fluorescence from free donors, free acceptors, and FRET pairs.
      Based upon the throughput in each emission channel as premeasured on pure samples
      of each of the three species, decoupling of an unknown sample's three polarized
      fluorescence images can be performed to calculate the pixel-by-pixel
      concentrations of donor, acceptor, and FRET pairs. The theory of this approach is
      presented here, and its feasibility is experimentally confirmed by measurements
      on mixtures of cyan fluorescent protein (CFP), citrine ((Cit) a yellow
      fluorescent protein variant), and linked fusion proteins (CFP-L16-Cit, CFP-L7
      Cit, CFP-L54-Cit) in living cells. The effects of shot noise, acceptor
      polarization, and FRET efficiency on the statistical accuracy of p-FRET
      experimental results are investigated by a noise-simulation program.

PMID- 15454471
TI  - Vesicle encapsulation studies reveal that single molecule ribozyme
      heterogeneities are intrinsic.
AB  - Single-molecule measurements have revealed that what were assumed to be identical
      molecules can differ significantly in their static and dynamic properties. One of
      the most striking examples is the hairpin ribozyme, which was shown to exhibit
      two to three orders of magnitude variation in folding kinetics between molecules.
      Although averaged behavior of single molecules matched the bulk solution data, it
      was not possible to exclude rigorously the possibility that the variations around
      the mean values arose from different ways of interacting with the surface
      environment. To test this, we minimized the molecules' interaction with the
      surface by encapsulating DNA or RNA molecules inside 100- to 200-nm diameter
      unilamellar vesicles, following the procedures described by Haran and coworkers.
      Vesicles were immobilized on a supported lipid bilayer via biotin-streptavidin
      linkages. We observed no direct binding of DNA or RNA on the supported bilayer
      even at concentrations exceeding 100 nM, indicating that these molecules do not
      bind stably on the membrane. Since the vesicle diameter is smaller than the
      resolution of optical microscopy, the lateral mobility of the molecules is
      severely constrained, allowing long observation periods. We used fluorescence
      correlation spectroscopy, nuclease digestion, and external buffer exchange to
      show that the molecules were indeed encapsulated within the vesicles. When
      contained within vesicles, the natural form of the hairpin ribozyme exhibited 50
      fold variation in both folding and unfolding rates in 0.5 mM Mg2+, which is
      identical to what was observed from the molecules tethered directly on the
      surface. This strongly indicates that the observed heterogeneity in dynamic
      properties does not arise as an artifact of surface attachment, but is intrinsic
      to the nature of the molecules.

PMID- 15454472
TI  - A fast global fitting algorithm for fluorescence lifetime imaging microscopy
      based on image segmentation.
AB  - Global fitting algorithms have been shown to improve effectively the accuracy and
      precision of the analysis of fluorescence lifetime imaging microscopy data.
      Global analysis performs better than unconstrained data fitting when prior
      information exists, such as the spatial invariance of the lifetimes of individual
      fluorescent species. The highly coupled nature of global analysis often results
      in a significantly slower convergence of the data fitting algorithm as compared
      with unconstrained analysis. Convergence speed can be greatly accelerated by
      providing appropriate initial guesses. Realizing that the image morphology often
      correlates with fluorophore distribution, a global fitting algorithm has been
      developed to assign initial guesses throughout an image based on a segmentation
      analysis. This algorithm was tested on both simulated data sets and time-domain
      lifetime measurements. We have successfully measured fluorophore distribution in
      fibroblasts stained with Hoechst and calcein. This method further allows second
      harmonic generation from collagen and elastin autofluorescence to be
      differentiated in fluorescence lifetime imaging microscopy images of ex vivo
      human skin. On our experimental measurement, this algorithm increased convergence
      speed by over two orders of magnitude and achieved significantly better fits.

PMID- 15454473
TI  - Direct comparison of the spread area, contractility, and migration of balb/c 3T3
      fibroblasts adhered to fibronectin- and RGD-modified substrata.
AB  - Native proteins are often substituted by short peptide sequences. These peptides
      can recapitulate key, but not all biofunctional properties of the native
      proteins. Here, we quantify the similarities and differences in spread area,
      contractile activity, and migration speed for balb/c 3T3 fibroblasts adhered to
      fibronectin- (FN) and Arg-Gly-Asp (RGD)-modified substrata of varying surface
      density. In both cases spread area has a biphasic dependence on surface ligand
      density (sigma) with a maximum at sigma approximately 200 molecules/microm2,
      whereas the total traction force increases and reaches a plateau as a function of
      sigma. In addition to these qualitative similarities, there are significant
      quantitative differences between fibroblasts adhered to FN and RGD. For example,
      fibroblasts on FN have a spread area that is on average greater by approximately
      200 microm2 over a approximately 40-fold change in sigma. In addition,
      fibroblasts on FN exert approximately 3-5 times more total force, which reaches a
      maximum at a value of sigma approximately 5 times less than for cells adhered to
      RGD. The data also indicate that the differences in traction are not simply a
      function of the degree of spreading. In fact, fibroblasts on FN (sigma
      approximately 2000 microm(-2)) and RGD (sigma approximately 200 microm(-2)) have
      both similar spread area (approximately 600 microm2) and migration speed
      (approximately 11 microm/h), yet the total force production is five times higher
      on FN than RGD (approximately 0.05 dyn compared to approximately 0.01 dyn). Thus,
      the specific interactions between fibroblasts and FN molecules must inherently
      allow for higher traction force generation in comparison to the interactions
      between fibroblasts and RGD.

PMID- 15454474
TI  - Biomechanics of Schlemm's canal endothelial cells: influence on F-actin
      architecture.
AB  - Aqueous humor drains from the eye through Schlemm's canal, a small endothelial
      lined collecting duct. Schlemm's canal endothelial cells may be important in
      controlling the pressure within the eye (and hence are of interest in glaucoma),
      and are subject to an unusual combination of shear stress and a basal-to-apical
      pressure gradient. We sought to characterize this biomechanical environment and
      determine its effects on F-actin architecture in situ. A theoretical model of
      flow in Schlemm's canal was used to estimate shear stresses applied to
      endothelial cells by flowing aqueous humor. Alignment of Schlemm's canal
      endothelial cells in human eyes was quantified by scanning electron microscopy. F
      actin architecture was visualized by fluorescent labeling and compared for
      closely adjacent cells exposed to different biomechanical environments. We found
      that, despite the relatively low flow rate of aqueous humor, shear stresses
      experienced by Schlemm's canal endothelial cells could reach those in the
      arterial system. Schlemm's canal endothelial cells showed a statistically
      significant preferential alignment, consistent with a shear-mediated effect.
      Schlemm's canal endothelial cells subjected to a basal-to-apical pressure
      gradient due to transendothelial flow showed a prominent marginal band of F-actin
      with relatively few cytoplasmic filaments. Adjacent cells not subject to this
      gradient showed little marginal F-actin, with a denser cytoplasmic random
      network. We conclude that Schlemm's canal endothelial cells experience
      physiologically significant levels of shear stress, promoting cell alignment. We
      speculate that this may help control the calibre of Schlemm's canal. F-actin
      distribution depends critically on the presence or absence of transendothelial
      flow and its associated pressure gradient. In the case of this pressure gradient,
      mechanical reinforcement around the cell periphery by F-actin seems to be
      critical.

PMID- 15454475
TI  - Force generation by cytoskeletal filament end-tracking proteins.
AB  - Force generation in several types of cell motility is driven by rapidly
      elongating cytoskeletal filaments that are persistently tethered at their
      polymerizing ends to propelled objects. These properties are not easily explained
      by force-generation models that require free (i.e., untethered) filament ends to
      fluctuate away from the surface for addition of new monomers. In contrast,
      filament end-tracking proteins that processively advance on filament ends can
      facilitate rapid elongation and substantial force generation by persistently
      tethered filaments. Such processive end-tracking proteins, termed here filament
      end-tracking motors, maintain possession of filament ends and, like other
      biomolecular motors, advance by means of 5'-nucleoside triphosphate (NTP)
      hydrolysis-driven affinity-modulated interactions. On-filament NTP
      hydrolysis/phosphate release yields substantially more energy than that required
      for driving steady-state assembly/disassembly of free filament ends (i.e.,
      filament treadmilling), as revealed by an energy inventory on the treadmilling
      cycle. The kinetic and thermodynamic properties of two simple end-tracking
      mechanisms (an end-tracking stepping motor and a direct-transfer end-tracking
      motor) are analyzed to illustrate the advantages of an end-tracking motor over
      free filament-end elongation, and over passive end-trackers that operate without
      the benefit of NTP hydrolysis, in terms of generating force, facilitating rapid
      monomer addition, and maintaining tight possession of the filament ends. We
      describe an additional cofactor-assisted end-tracking motor to account for
      suggested roles of cofactors in the affinity-modulated interactions, such as
      profilin in actin-filament end-tracking motors and EB1 in microtubule end
      tracking motors.

PMID- 15454476
TI  - Enforced detachment of red blood cells adhering to surfaces: statics and
      dynamics.
AB  - We investigated the mechanical strength of adhesion and the dynamics of unbinding
      of red blood cells to solid surfaces. Two different situations were tested: 1),
      native red blood cells nonspecifically adhered to glass surfaces coated with
      positively charged polymers and 2), biotinylated red blood cells specifically
      adhered to glass surfaces decorated with streptavidin, which has a high binding
      affinity for biotin. We used micropipette manipulation for forming and
      subsequently breaking the adhesive contact through a stepwise micromechanical
      procedure. Analysis of cell deformations provided the relation between force and
      contact radius, which was found to be in good agreement with theoretical
      predictions. We further demonstrated that the separation energy could be
      precisely derived from the measure of rupture forces and the cell shape. Finally,
      the dynamics of detachment was analyzed as a function of the applied force and
      the initial size of the adhesive patch. Our experiments were supported by
      original theoretical predictions, which allowed us to correlate the measured
      separation times with the molecular parameters (e.g., activation barrier,
      receptor-ligand characteristic length) derived from force measurements at the
      single bond level.

PMID- 15454477
TI  - Estimating the sensitivity of mechanosensitive ion channels to membrane strain
      and tension.
AB  - Bone adapts to its environment by a process in which osteoblasts and osteocytes
      sense applied mechanical strain. One possible pathway for the detection of strain
      involves mechanosensitive channels and we sought to determine their sensitivity
      to membrane strain and tension. We used a combination of experimental and
      computational modeling techniques to gain new insights into cell mechanics and
      the regulation of mechanosensitive channels. Using patch-clamp electrophysiology
      combined with video microscopy, we recorded simultaneously the evolution of
      membrane extensions into the micropipette, applied pressure, and membrane
      currents. Nonselective mechanosensitive cation channels with a conductance of 15
      pS were observed. Bleb aspiration into the micropipette was simulated using
      finite element models incorporating the cytoplasm, the actin cortex, the plasma
      membrane, cellular stiffening in response to strain, and adhesion between the
      membrane and the micropipette. Using this model, we examine the relative
      importance of the different cellular components in resisting suction into the
      pipette and estimate the membrane strains and tensions needed to open
      mechanosensitive channels. Radial membrane strains of 800% and tensions of 5 10(
      4) N.m(-1) were needed to open 50% of mechanosensitive channels. We discuss the
      relevance of these results in the understanding of cellular reactions to
      mechanical strain and bone physiology.

PMID- 15454478
TI  - Q-band EPR of the S2 state of photosystem II confirms an S = 5/2 origin of the X
      band g = 4.1 signal.
AB  - Disagreement has remained about the spin state origin of the g = 4.1 EPR signal
      observed at X-band (9 GHz) from the S2 oxidation state of the Mn cluster of
      Photosystem II. In this study, the S2 state of PSII-enriched membrane fragments
      was examined at Q-band (34 GHz), with special interest in low-field signals.
      Light-induced signals at g = 3.1 and g = 4.6 were observed. The intensity of the
      signal at g = 3.1 was enhanced by the presence of F- and suppressed by the
      presence of 5% ethanol, indicating that it was from the same spin system as the X
      band signal at g = 4.1. The Q-band signal at g = 4.6 was also enhanced by F-, but
      not suppressed by 5% ethanol, making its identity less clear. Although it can be
      accounted for by the same spin system, other sources for the signal are
      considered. The observation of the signal at g = 3.1 agrees well with a previous
      study at 15.5 GHz, in which the X-band g = 4.1 signal was proposed to arise from
      the middle Kramers doublet of a near rhombic S = 5/2 system. Zero-field splitting
      values of D = 0.455 cm(-1) and E/D = 0.25 are used to simulate the spectra.

PMID- 15454479
TI  - Adsorption of divalent cations on DNA.
AB  - The distribution of divalent ions in semidilute solutions of high-molecular-mass
      DNA containing both sodium chloride and strontium chloride in near-physiological
      conditions is studied by small-angle x-ray scattering and by small-angle neutron
      scattering. Both small-angle neutron scattering and small-angle x-ray scattering
      reveal a continuous increase in the scattering intensity at low q with increasing
      divalent ion concentration, while at high q the scattering curves converge. The
      best fit to the data is found for a configuration in which DNA strands of cross
      sectional radius 10 angstroms are surrounded by a counterion sheath of outer
      radius approximately 13.8 angstroms, independent of the strontium chloride
      concentration. When the strontium chloride is replaced by calcium chloride,
      similar results are obtained, but the thickness of the sheath increases when the
      divalent salt concentration decreases. These results correspond in both cases to
      partial localization of the counterions within a layer that is thinner than the
      effective Debye screening length.

PMID- 15454480
TI  - Leukotriene B4 plays a pivotal role in CD40-dependent activation of chronic B
      lymphocytic leukemia cells.
AB  - Biosynthesis of leukotrienes (LTs) occurs in human myeloid cells and B
      lymphocytes. However, the function of leukotrienes in B lymphocytes is unclear.
      Here, we report that B-cell chronic lymphocytic leukemia (B-CLL) cells produce
      leukotriene B(4), and that specific leukotriene biosynthesis inhibitors
      counteracted CD40-dependent activation of B-CLL cells. Studies on the expression
      of the high-affinity receptor for LTB(4) (BLT1) by flow cytometry analysis showed
      that the receptor was expressed, to a varying degree, in all investigated B-CLL
      clones. At a concentration of 100 nM, the drugs BWA4C (a specific 5-lipoxygenase
      inhibitor) and MK-886 (a specific 5-lipoxygenase activating protein inhibitor)
      markedly inhibited CD40-induced DNA synthesis (45% and 38%, respectively) and
      CD40-induced expression of CD23, CD54, and CD150. Addition of exogenous LTB(4)
      (150 nM) almost completely reversed the effect of the inhibitors on DNA synthesis
      and antigen expression. Taken together, the results of the present study suggest
      that leukotriene biosynthesis inhibitors may have a therapeutic role in B-CLL.

PMID- 15454481
TI  - Final adult height of patients who received hematopoietic cell transplantation in
      childhood.
AB  - Growth impairment and growth hormone (GH) deficiency are complications after
      total body irradiation (TBI) and hematopoietic cell transplantation (HCT). To
      determine the impact of GH therapy on growth, the final heights of 90 GH
      deficient children who underwent fractionated TBI and HCT for malignancy were
      evaluated. Changes in height standard deviation (SD) from the diagnosis of GH
      deficiency to the achievement of final height were compared among 42 who did and
      48 who did not receive GH therapy. At HCT, GH-treated patients were younger (P =
      .001), more likely to have undergone central nervous system irradiation (P =
      .007), and shorter (P = .005) than patients who did not receive GH therapy. After
      HCT, GH deficiency was diagnosed at 1.5 years (range, 0.8-9.5 years) for GH
      treated and 1.2 years (range, 0.9-8.8 years) for nontreated patients. GH therapy
      was associated with significantly improved final height in children younger than
      10 years at HCT (P = .0001), but GH therapy did not impact the growth of older
      children. Girls (P = .0001) and children diagnosed with acute myelogenous
      leukemia (AML), chronic myelogenous leukemia (CML), or myelodysplastic syndromes
      (MDS) (compared with acute lymphoblastic leukemia [ALL] or non-Hodgkin lymphoma
      [NHL]; P = .02) also showed more rapid growth than their counterparts. These data
      demonstrate that GH therapy improves the final height of young children after
      fractionated TBI.

PMID- 15454482
TI  - Cannabis-induced cytotoxicity in leukemic cell lines: the role of the cannabinoid
      receptors and the MAPK pathway.
AB  - Delta9-Tetrahydrocannabinol (THC) is the active metabolite of cannabis. THC
      causes cell death in vitro through the activation of complex signal transduction
      pathways. However, the role that the cannabinoid 1 and 2 receptors (CB1-R and CB2
      R) play in this process is less clear. We therefore investigated the role of the
      CB-Rs in mediating apoptosis in 3 leukemic cell lines and performed microarray
      and immunoblot analyses to establish further the mechanism of cell death. We
      developed a novel flow cytometric technique of measuring the expression of
      functional receptors and used combinations of selective CB1-R and CB2-R
      antagonists and agonists to determine their individual roles in this process. We
      have shown that THC is a potent inducer of apoptosis, even at 1 x IC(50)
      (inhibitory concentration 50%) concentrations and as early as 6 hours after
      exposure to the drug. These effects were seen in leukemic cell lines (CEM, HEL
      92, and HL60) as well as in peripheral blood mononuclear cells. Additionally, THC
      did not appear to act synergistically with cytotoxic agents such as cisplatin.
      One of the most intriguing findings was that THC-induced cell death was preceded
      by significant changes in the expression of genes involved in the mitogen
      activated protein kinase (MAPK) signal transduction pathways. Both apoptosis and
      gene expression changes were altered independent of p53 and the CB-Rs.

PMID- 15454483
TI  - Quantitative analysis of nucleoside transporter and metabolism gene expression in
      chronic lymphocytic leukemia (CLL): identification of fludarabine-sensitive and 
      insensitive populations.
AB  - Resistance to fludarabine is observed in the clinic, and molecular predictive
      assays for benefit from chemotherapy are required. Our objective was to determine
      if expression of nucleoside transport and metabolism genes was associated with
      response to fludarabine therapy in patients with chronic lymphocytic leukemia
      (CLL). CLL cells from 56 patients were collected prior to treatment with
      fludarabine. Quantitative reverse transcriptase-polymerase chain reaction (RT
      PCR) was performed on sample RNA to determine the relative levels of mRNA of 3
      nucleoside transporters that mediate fludarabine uptake (human equilibrative
      nucleoside transporter 1 [hENT1], human equilibrative nucleoside transporter 2
      [hENT2], and human concentrative nucleoside transporter 3 [hCNT3]), deoxycytidine
      kinase (dCK), and 3 5'-nucleotidases (ecto-5'nucleotidase [CD73],
      deoxynucleotidase-1 [dNT-1], and cytoplasmic high-Km 5-nucleotidase [CN-II]). Two
      dimensional hierarchical cluster analysis of gene expression identified 2
      distinct populations of CLL. Cluster 2 patients experienced a 3.4-fold higher
      risk of disease progression than cluster 1 patients (P = .0058, log-rank
      analysis). Furthermore, independent analysis of the individual genes of interest
      revealed statistically significant differences for risk of disease progression
      (adjusted hazard ratios [HRs]) with underexpression of dNT-1 (HR = 0.45; P =
      .042), CD73 (HR = 0.40; P = .022), and dCK (HR = 0.0.48; P = .035), and
      overexpression of hCNT3 (HR = 4.7; P = .0007) genes. Subjects with elevated hCNT3
      expression experienced a lower complete response rate to fludarabine therapy (11%
      vs 69%; P = .002). No hCNT3-mediated plasma membrane nucleoside transport was
      detected in CLL samples expressing hCNT3 message, and hCNT3 protein was localized
      to the cytoplasm with immunohistochemical and confocal microscopy.

PMID- 15454484
TI  - Chemokine receptor expression in EBV-associated lymphoproliferation in hu/SCID
      mice: implications for CXCL12/CXCR4 axis in lymphoma generation.
AB  - The mechanisms by which intraperitoneal injection of peripheral blood mono
      nuclear cells (PBMCs) from Epstein-Barr virus (EBV)-seropositive donors into
      severe combined immunodeficient (SCID) mice gives rise to lymphomas (hu/SCID
      tumors) are far from clear. This study addressed whether chemokine receptors and
      their ligands could be implicated in this experimental model. CXCR4 was found to
      be highly expressed in hu/SCID tumors; surface expression of CXCR4 was
      prevalently limited to a tumor cell subset poorly expressing CD23, whereas the
      CXCR4 ligand, CXCL12, was predominantly expressed by the tumor subpopulation
      expressing CD23. In vitro inhibition of this autocrine/paracrine CXCL12/CXCR4
      axis significantly inhibited lymphoma proliferation and survival. Furthermore,
      CXCL12 was expressed in cells recovered from the mouse peritoneal cavity early
      after PBMC transfer as well as by EBV-transformed B cells but not by resting or
      activated B lymphocytes; also, lymphoma development was associated with a
      dramatic increase in the levels of murine CXCL12 present in the peritoneal
      cavity. Finally, antagonizing the CXCL12/CXCR4 axis in vivo strongly counteracted
      lymphoma development. These studies demonstrate that CXCL12 expression may be
      associated with EBV infection and suggest that the CXCR4/CXCL12 axis may
      participate in the EBV-associated lymphomagenesis process in immunodeficient
      hosts.

PMID- 15454485
TI  - Mortality in sickle cell patients on hydroxyurea therapy.
AB  - The efficacy of hydroxyurea (HU) and its role in the reduction in mortality in
      sickle cell patients has been established. Nevertheless, many patients still die
      of complications of this disease while on HU. Of the 226 patients treated with HU
      at our center, 38 died (34 of sickle cell-related causes). Acute chest syndrome
      (ACS) was the most common (35%) cause of death. Deceased and surviving patients
      did not differ significantly in average HU dose, baseline fetal hemoglobin (Hb
      F), or maximum Hb F response. However, the deceased patients were significantly
      older when HU was instituted, were more anemic, and more likely to have BAN or
      CAM haplotypes. They also had significantly higher serum blood-urea-nitrogen
      (BUN) and creatinine levels. Sickle cell patients who die while on HU therapy may
      represent a subgroup of older patients, possibly with more severe disease and
      more severe organ damage. Such patients need early identification and prompt HU
      institution.

PMID- 15454486
TI  - Imatinib mesylate (STI-571) enhances antigen-presenting cell function and
      overcomes tumor-induced CD4+ T-cell tolerance.
AB  - Tumor antigen-specific T-cell tolerance imposes a significant barrier to the
      development of effective therapeutic cancer vaccines. Bone marrow-derived antigen
      presenting cells (APCs) are critical in the induction of this unresponsive state.
      Here we show that in vitro treatment of APCs with the tyrosine kinase inhibitor,
      imatinib mesylate (STI-571), enhances the activation of naive antigen-specific T
      cells and restores the responsiveness of tolerant T cells from tumor-bearing
      hosts. Furthermore, in vivo treatment with STI-571 not only prevented the
      induction of tolerance in tumor-specific CD4(+) T cells, preserving their
      responsiveness to a subsequent immunization, but also resulted in enhanced
      vaccine efficacy. These findings demonstrate that tolerance to tumor antigens is
      not an insurmountable obstacle and points to modulation of APC function as a
      promising strategy in the immunotherapy of cancer.

PMID- 15454487
TI  - IL-8 and its CXCR1 and CXCR2 receptors participate in the control of
      megakaryocytic proliferation, differentiation, and ploidy in myeloid metaplasia
      with myelofibrosis.
AB  - Myeloproliferation, myelofibrosis, and neoangiogenesis are the 3 major intrinsic
      pathophysiologic features of myeloid metaplasia with myelofibrosis (MMM). The
      myeloproliferation is characterized by an increased number of circulating CD34+
      progenitors with the prominent amplification of dystrophic megakaryocytic (MK)
      cells and myeloid metaplasia in the spleen and liver. The various biologic
      activities of interleukin 8 (IL-8) in hematopoietic progenitor proliferation and
      mobilization as well as in neoangiogenesis prompted us to analyze its potential
      role in MMM. We showed that the level of IL-8 chemokine is significantly
      increased in the serum of patients and that various hematopoietic cells,
      including platelets, participate in its production. In vitro inhibition of
      autocrine IL-8 expressed by CD34+ cells with either a neutralizing or an
      antisense anti-IL-8 treatment increases the proliferation of MMM CD34(+)-derived
      cells and stimulates their MK differentiation. Moreover, addition of neutralizing
      anti-IL-8 receptor (CXC chemokine receptor 1 [CXCR1] or 2 [CXCR2]) antibodies to
      MMM CD34+ cells cultured under MK liquid culture conditions increases the
      proliferation and differentiation of MMM CD41+ MK cells and restores their
      polyploidization. Our results suggest that IL-8 and its receptors participate in
      the altered MK growth that features MMM and open new therapeutic prospects for
      this still incurable disease.

PMID- 15454488
TI  - Functional defect of regulatory CD4(+)CD25+ T cells in the thymus of patients
      with autoimmune myasthenia gravis.
AB  - Thymus-derived CD4(+)CD25+ regulatory T (Treg) cells are essential for the
      maintenance of immunologic self-tolerance. Despite their critical role in the
      active suppression of experimental autoimmune disorders, little is known about
      their involvement in human autoimmune diseases. Myasthenia gravis (MG) is a CD4+
      T cell-dependent autoimmune disease and the thymus is assumed to be the
      initiation site. To identify possible defects in the Treg cells in MG, we
      analyzed CD4(+)CD25+ cells in thymi from patients with MG compared to those from
      healthy subjects. We found a normal CD4(+)CD25+ number but a severe functional
      defect in their regulatory activity together with a decreased expression of the
      transcription factor, Foxp3, which is essential for T-cell regulatory function.
      The phenotypic analysis of CD4(+)CD25+ thymocytes revealed an increased number of
      activated effector cells with strong Fas expression in patients with MG. However,
      whatever their level of Fas, CD4(+)CD25+ thymocytes from patients with MG
      remained unable to suppress the proliferation of responding cells, indicating
      that the impaired Treg cell function is not due to contamination by activated
      effector T cells. These data are the first to demonstrate a severe functional
      impairment of thymic Treg cells in MG, which could contribute to the onset of
      this autoimmune disease.

PMID- 15454489
TI  - A novel celecoxib derivative, OSU03012, induces cytotoxicity in primary CLL cells
      and transformed B-cell lymphoma cell line via a caspase- and Bcl-2-independent
      mechanism.
AB  - Chronic lymphocytic leukemia (CLL) is an incurable adult leukemia characterized
      by disrupted apoptosis. OSU03012 is a bioavailable third-generation celecoxib
      derivative devoid of cyclooxygenase-2 inhibitory activity that potently induces
      apoptosis in prostate cancer cell lines and is being developed as an anticancer
      therapy in the National Cancer Institute (NCI) Rapid Access to Intervention
      Development (RAID) program. We assessed the ability of OSU03012 to induce
      apoptosis in primary CLL cells and the mechanism by which this occurs. The LC50
      (lethal concentration 50%) of OSU03012 at 24 hours was 7.1 microM, and this
      decreased to 5.5 microM at 72 hours. Additionally, we have demonstrated that
      OSU03012 mediates apoptosis by activation of the intrinsic, mitochondrial pathway
      of apoptosis but also activates alternative cell death pathways that are caspase
      independent. The early activation of both caspase-dependent and -independent
      pathways of apoptosis is novel to OSU03012 and suggests it has great potential
      promise for the treatment of CLL. Moreover, unlike the great majority of
      therapeutic agents used to treat leukemia or other forms of cancer, OSU03012
      induces cell death entirely independent of bcl-2 expression. Overall, these data
      provide justification for further preclinical development of OSU03012 as a
      potential therapeutic agent for CLL.

PMID- 15454490
TI  - SPI-CI and SPI-6 cooperate in the protection from effector cell-mediated
      cytotoxicity.
AB  - Tumors have several mechanisms to escape from the immune system. One of these
      involves expression of intracellular anticytotoxic proteins that modulate the
      execution of cell death. Previously, we have shown that the serine protease
      inhibitor (serpin) SPI-6, which inactivates the cytotoxic protease granzyme B
      (GrB), is capable of preventing cytotoxic T lymphocyte (CTL)-mediated apoptosis.
      Despite its potent antiapoptotic activity, SPI-6 does not prevent membranolysis
      induced by cytotoxic lymphocytes. We now provide evidence that several colon
      carcinoma cell lines do resist membranolysis and that this protection is
      dependent on SPI-6 but also requires expression of a closely related serpin
      called SPI-CI (serine protease inhibitor involved in cytotoxicity inhibition).
      Expression of SPI-CI is absent from normal colon but observed in placenta,
      testis, early during embryogenesis, and in cytotoxic lymphocytes. SPI-CI encodes
      a chymotrypsin-specific inhibitor and irreversibly interacts with purified
      granzyme M. Moreover, SPI-CI can protect cells from purified perforin/GrM-induced
      lysis. Our data therefore indicate that SPI-CI is a novel immune escape molecule
      that acts in concert with SPI-6 to prevent cytotoxic lymphocyte-mediated killing
      of tumor cells.

PMID- 15454491
TI  - Regulated interaction of the Fanconi anemia protein, FANCD2, with chromatin.
AB  - DNA damage activates the monoubiquitination of the Fanconi anemia (FA) protein,
      FANCD2, resulting in the assembly of FANCD2 nuclear foci. In the current study,
      we characterize structural features of FANCD2 required for this intranuclear
      translocation. We have previously identified 2 normal mRNA splice variants of
      FANCD2, one containing exon 44 sequence at the 3' end (FANCD2-44) and one
      containing exon 43 sequence (FANCD2-43). The 2 predicted FANCD2 proteins differ
      in their carboxy terminal 24 amino acids. In stably transfected FANCD2(-/-)
      fibroblasts, FANCD2-44 and FANCD2-43 proteins were monoubiquitinated on K561.
      Only FANCD2-44 corrected the mitomycin C (MMC) sensitivity of the transfected
      cells. We find that monoubiquitinated FANCD2-44 was translocated from the soluble
      nuclear compartment into chromatin. A mutant form of FANCD2-44 (FANCD2-K561R) was
      not monoubiquitinated and failed to bind chromatin. A truncated FANCD2 protein
      (Exon44-T), lacking the carboxy terminal 24 amino acids encoded by exon 44 but
      retaining K561, and another mutant FANCD2 protein, with a single amino acid
      substitution at a conserved residue within the C-terminal 24 amino acids
      (D1428A), were monoubiquitinated. Both mutants were targeted to chromatin but
      failed to correct MMC sensitivity. Taken together, our results indicate that
      monoubiquitination of FANCD2 regulates chromatin binding and that D1428 within
      the carboxy terminal acidic sequence encoded by exon 44 is independently required
      for functional complementation of FA-D2 cells. We hypothesize that the carboxy
      terminus of FANCD2-44 plays a critical role in sensing or repairing DNA damage.

PMID- 15454492
TI  - Influence of CD33 expression levels and ITIM-dependent internalization on
      gemtuzumab ozogamicin-induced cytotoxicity.
AB  - Gemtuzumab ozogamicin (GO; Mylotarg), a novel immunoconjugate used for treatment
      of acute myeloid leukemia (AML), contains the humanized anti-CD33 antibody
      (hP67.6) as a carrier to facilitate cellular uptake of the toxic calicheamicin
      gamma(1) derivative. By use of lentivirus-mediated gene transfer to manipulate
      CD33 expression in myeloid cell lines that normally lack CD33 (murine 32D cells)
      or have very low levels of CD33 (human OCI-AML3 and KG-1a cells), we here show a
      quantitative relationship between CD33 expression and GO-induced cytotoxicity.
      The CD33 cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs)
      control internalization of antibody bound to CD33. Disruption of the ITIMs by
      introduction of point mutations not only prevented effective internalization of
      antibody-bound CD33 but also significantly reduced GO-induced cytotoxicity.
      Together, our data imply a pivotal role of both the number of CD33 molecules
      expressed on the cell surface and the amount of internalization of CD33 following
      antibody binding for GO-induced cytotoxicity and suggest novel therapeutic
      approaches for improvement of clinical outcome of patients treated with GO.

PMID- 15454493
TI  - Identification of cooperative genes for NUP98-HOXA9 in myeloid leukemogenesis
      using a mouse model.
AB  - The chromosomal translocation t(7; 11)(p15;p15), observed in human myeloid
      leukemia, results in a NUP98 and HOXA9 gene fusion. We generated a transgenic
      mouse line that specifically expressed the chimeric NUP98-HOXA9 gene in the
      myeloid lineage. While only 20% of the transgenic mice progressed to leukemia
      after a latency period, myeloid progenitor cells from nonleukemic transgenic mice
      still exhibited increased proliferative potential. This suggested that the NUP98
      HOXA9 fusion induced a preleukemic phase, and other factors were required for
      complete leukemogenesis. NUP98-HOXA9 expression promoted the onset of retrovirus
      induced BXH2 myeloid leukemia. This phenomenon was used to identify cooperative
      disease genes as common integration sites (CISs). Meis1, a known HOX cofactor,
      was identified as a CIS with a higher integration frequency in transgenic than in
      wild-type BXH2 mice. By the same means we identified further 4 candidate
      cooperative genes, Dnalc4, Fcgr2b, Fcrl, and Con1. These genes cooperated with
      NUP98-HOXA9 in transforming NIH 3T3 cells. The system described here is a
      powerful tool to identify cooperative oncogenes and will assist in the
      clarification of the multistep process of carcinogenesis.

PMID- 15454494
TI  - Targeting NF-kappaB activation via pharmacologic inhibition of IKK2-induced
      apoptosis of human acute myeloid leukemia cells.
AB  - Acute myeloid leukemia (AML) cells are characterized by a constitutive and
      abnormal activation of the nuclear factor-kappaB (NF-kappaB) transcription
      factor. This study, conducted in vitro on 18 patients, shows that targeting the
      IKB kinase 2 (IKK2) kinase with the specific pharmacologic inhibitor AS602868 to
      block NF-kappaB activation led to apoptosis of human primary AML cells. Moreover,
      AS602868 potentiated the apoptotic response induced by the current
      chemotherapeutic drugs doxorubicin, cytarabine, or etoposide (VP16). AS602868
      induced cell death was associated with rupture of the mitochondrial transmembrane
      potential and activation of cellular caspases. NF-kappaB inhibition did not
      affect normal CD34+ hematopoietic precursors, suggesting that it could represent
      a new adjuvant strategy for AML treatment.

PMID- 15454496
TI  - Looking without listening: is audition a prerequisite for normal development of
      visual attention during infancy?
AB  - Potential effects of auditory and other communicative experience on development
      of visual attention were investigated for four groups of infants at 9, 12, and 18
      months of age. Participants included 20 deaf infants with deaf mothers, 19 deaf
      infants with hearing mothers, 21 hearing infants with hearing mothers, and 20
      hearing infants with deaf mothers. Infants' hearing status alone did not
      associate with patterns of visual attention. Deaf infants with deaf mothers
      showed significantly longer times in the most advanced attention state
      (coordinated joint) than did deaf infants with hearing mothers. However, other
      aspects of experience were associated with group differences. Both deaf and
      hearing children with deaf mothers who signed spent more time onlooking (or
      watching) their mothers than did children (deaf or hearing) with hearing mothers.
      Hearing children with hearing mothers spent more time looking at objects than did
      children with deaf mothers. Despite these differences in time in various
      attention states, the general trajectory of development of each of the attention
      states was similar across groups. Results indicate that early visual attention is
      associated with and potentially influenced by a complex interaction of
      maturation, communicative experiences, and other developing skills.

PMID- 15454495
TI  - Prospective observational study on the incidence of medication errors during
      simulated resuscitation in a paediatric emergency department.
AB  - OBJECTIVES: To characterise the incidence and nature of medication errors during
      paediatric resuscitations. DESIGN: A prospective observational study of simulated
      emergencies. SETTING: Emergency department of a tertiary paediatric hospital.
      PARTICIPANTS: Teams that included a clinician who commonly leads "real"
      resuscitations, at least two assisting physicians, and two or three paediatric
      nurses. INTERVENTIONS: The teams conducted eight mock resuscitations, including
      ordering medications. Exercises were videotaped and drugs ordered and
      administered during the resuscitation were recorded. Syringes and drugs prepared
      during the resuscitation were collected and analysed for concentrations and
      actual amounts. MAIN OUTCOME MEASURES: Number and type of drug errors. RESULTS:
      Participants gave 125 orders for medications. In 21 (17%) of the orders the exact
      dose was not specified. Nine dosing errors occurred during the ordering phase. Of
      these errors, five were intercepted before the drug reached the patient. Four 10
      fold errors were identified. In nine (16%) out of 58 syringes analysed, measured
      drug concentrations showed a deviation of at least 20% from the ordered dose. A
      large deviation (at least 50%) from the expected dose was found in four (7%)
      cases. CONCLUSIONS: Medication errors commonly occur during all stages of
      paediatric resuscitation. Many errors could be detected only by analysing syringe
      content, suggesting that such errors may be a major source of morbidity and
      mortality in resuscitated children.

PMID- 15454497
TI  - Conversations between deaf children and their hearing mothers: pragmatic and
      dialogic characteristics.
AB  - We examined communication between hearing mothers and their deaf or hearing
      children longitudinally at child-ages 22 months and 3 years. Specifically, we
      analyzed both the effects of child deafness and developmental change on pragmatic
      and dialogic characteristics of communication. From 22 months to 3 years, deaf
      and hearing children's communicative skills improved similarly along some
      dimensions: as they grew older, both deaf and hearing children increased the
      amount they communicated, became increasingly responsive to their mothers'
      attentional focus, and were responsible for initiating a higher proportion of the
      dyads' conversations. On the other hand, deaf children were less skilled at
      maintaining topics, and the pragmatic function of their communication was more
      likely to be unclear compared to hearing children. Deaf children were also more
      likely to direct their mothers and less likely to ask questions than hearing
      children. Communication by hearing mothers was primarily examined to determine
      the degree to which they controlled the interactions. Overall, mothers of deaf
      children were only more controlling along one dimension. Mothers of deaf children
      used more response controls than mothers of hearing children. However, the
      majority of measures suggested they did not exert more topic or turn-taking
      controls than did mothers of hearing children. In addition, mothers of deaf and
      hearing children seemed equally sensitive to their children's communication
      abilities. Communication by mothers of both deaf and hearing children changed in
      similar ways as their children developed. Most of the differences in
      communication by mothers of deaf and hearing children seemed attributable to the
      deaf children's linguistic delays. The results suggest that intervention efforts
      should be focused on fostering linguistic development and not general
      communication skills or changing maternal conversational control.

PMID- 15454498
TI  - Promoting social competence in deaf students: the effect of an intervention
      program.
AB  - The aim of this study was to determine the effects of a social skills training
      program on the social skills and social behaviors of deaf children in a
      mainstream setting. The study used a pretest/posttest design. The participants
      consisted of 18 severely and profoundly hearing-impaired children (ages ranged
      from 9;1 to 13;6) who were enrolled in three elementary schools in the Canary
      Islands. Results indicated that the intervention succeeded in improving students'
      social problem-solving skills, especially in making comprehensible the steps
      implied in the solution of interpersonal problems; the intervention also led to
      significant improvement of deaf students' assertive behavior as rated by their
      teachers and by themselves. Significant differences in social or academic
      integration as judged by companions in a sociometric questionnaire were not
      found.

PMID- 15454499
TI  - The Stanford Achievement Test, 9th Edition: National Norming and Performance
      Standards for Deaf and Hard-of-Hearing Students.
AB  - This article presents a rich context of information for interpreting Stanford
      Achievement Test scores and for describing the achievement of deaf and hard-of
      hearing students. The publisher's national norming of the Stanford Achievement
      Test provides a context of actual performance of hearing students. The
      publisher's Performance Standards provide a context of expectations for hearing
      students as determined by a panel of experts. The Gallaudet Research Institute's
      norming of the test on a national sample of deaf and hard-of-hearing students
      provides a context of test performance by this special population. A smaller
      subsample of the deaf and hard-of-hearing students who take the same test levels
      as hearing students provides an additional reference group with respect to the
      Performance Standards. Information from these sources is brought together into
      two graphical contexts to address these questions: Can the normative data from
      the publisher's national standardization of the test with hearing students, and
      the normative data from the GRI's national norming of the test with deaf and hard
      of-hearing students provide a useful context for the interpretation of individual
      test scores? Can they provide a useful way to examine achievement of groups of
      students? Can the new Performance Standards defined by the test publisher offer a
      useful context for test score interpretation for high-achieving deaf and hard-of
      hearing students?

PMID- 15454500
TI  - A developmental model applied to problems of deafness.
AB  - From the Editors: This article represents another in our series of "classics"
      that helped to shape the field of deaf studies and deaf education. The article
      first appeared as Chapter Two in Sound and Sign: Childhood Deafness and Mental
      Health, H. S. Schlesinger and K. P. Meadow (1972), Berkeley: University of
      California Press. The book reported pioneering research and clinical mental
      health services at the Langley Porter Neuropsychiatric Institute, University of
      California, San Francisco. For current readers, some of the language may seem out
      of date, and the Editors have made several minor modifications to ensure that
      readers fully recognize the original intention of the author. (Such modifications
      are indicated by square brackets or ellipses for contemporary purposes, but the
      intentions of the original all have been maintained, and Editors' notes are
      indicated as such to distinguish them from the Authors' notes.) Nevertheless,
      many of the ideas are fresh and important. Indeed, some passages serve as
      particular reminders of significant changes in opportunities for and attitudes
      about Deaf people over the past three decades. Many of these changes resulted
      directly from the work of Dr. Schlesinger and her colleagues.

PMID- 15454501
TI  - All in the family.

PMID- 15454502
TI  - Deaf parents and their hearing children.
AB  - The focus of this review article is on families with Deaf parents and hearing
      children. We provide a brief description of the Deaf community, their language,
      and culture; describe communication patterns and parenting issues in Deaf
      parented families, examine the role of the hearing child in a Deaf family and how
      that experience affects their functioning in the hearing world; and discuss
      important considerations and resources for families, educators, and health care
      and service providers.

PMID- 15454503
TI  - The pragmatic skills of profoundly deaf children.
AB  - This study investigated the ability of normally hearing students and two groups
      of profoundly deaf students, one using oral and one using signed communication,
      to employ a series of pragmatic skills required for effective face-to-face
      interaction. Specifically considered were the ability of listeners to request
      clarification, the ability of speakers to respond to requests, and the strategies
      speakers use at times of communication breakdown. Differences were found between
      the two groups suggesting that the profoundly deaf students had difficulty
      consistently using appropriate, productive pragmatic behaviors in their face-to
      face dyadic interactions.

PMID- 15454504
TI  - Theory of Mind: Deaf and Hearing Children's Comprehension of Picture Stories and
      Judgments of Social Situations.
AB  - We compared 20 prelingually profoundly deaf adolescents (age: 11-16 years) and 20
      matched, hearing adolescents on a picture-sequencing task and on a social
      judgment test. In addition, we also tested 14 younger deaf children (age: 6-10
      years) and compared their data with those from 20 hearing peers as well as those
      from the older deaf participants on the picture-sequencing task. The results from
      this study did not provide evidence for the hypothesis that deaf adolescents
      possess significantly poorer knowledge about social reasoning than age-matched
      hearing peers, but it did present further additional support for Peterson and
      Siegal's (1995) conversational hypothesis: a proposal that a deprivation in
      conversations about mental states leads to an impairment in the development of an
      awareness of mental states in the younger deaf children.

PMID- 15454505
TI  - The impact of sign language on the cognitive development of deaf children: the
      case of theories of mind.
AB  - The ability to attribute false beliefs (i.e., demonstrate theory of mind) by 155
      deaf children between 5 and 8 years of age was compared to that of 39 hearing
      children ages 4 to 6. The hypotheses under investigation were (1) that linguistic
      features of sign language could promote the development of theories of mind and
      (2) that early exposure to language would allow an easier access to these
      theories. Deaf children were grouped according to their communication mode and
      the hearing status of their parents. The results obtained in three false belief
      tasks supported the hypotheses: effective representational abilities were
      demonstrated by deaf children of deaf parents, whereas those born to hearing
      parents appeared delayed in that regard, with differences according to their
      communication mode.

PMID- 15454506
TI  - Enhancing the Induction Skill of Deaf and Hard-of-Hearing Children with Virtual
      Reality Technology.
AB  - Many researchers have found that for reasoning and reaching a reasoned
      conclusion, particularly when the process of induction is required, deaf and hard
      of-hearing children have unusual difficulty. The purpose of this study was to
      investigate whether the practice of rotating virtual reality (VR) three
      dimensional (3D) objects will have a positive effect on the ability of deaf and
      hard-of-hearing children to use inductive processes when dealing with shapes.
      Three groups were involved in the study: (1) experimental group, which included
      21 deaf and hard-of-hearing children, who played a VR 3D game; (2) control group
      I, which included 23 deaf and hard-of-hearing children, who played a similar two
      dimensional (2D) game (not VR game); and (3) control group II of 16 hearing
      children for whom no intervention was introduced. The results clearly indicate
      that practicing with VR 3D spatial rotations significantly improved inductive
      thinking used by the experimental group for shapes as compared with the first
      control group, who did not significantly improve their performance. Also, prior
      to the VR 3D experience, the deaf and hard-of-hearing children attained lower
      scores in inductive abilities than the children with normal hearing, (control
      group II). The results for the experimental group, after the VR 3D experience,
      improved to the extent that there was no noticeable difference between them and
      the children with normal hearing.

PMID- 15454507
TI  - Computer and information technology access for deaf individuals in developed and
      developing countries.

PMID- 15454508
TI  - Tactile Contact by Deaf and Hearing Mothers During Face-to-Face Interactions With
      Their Infants.
AB  - Tactile contact with an infant plays an important role (though one largely
      overlooked by researchers until recently) in the development of synchronous
      interactive dialogues between caregiver and child. Dyads in which one or both
      partners are deaf present a unique opportunity to examine the use of touch as a
      means of optimizing or enhancing communication when the number of available
      sensory channels is restricted. Touch in these dyads may play an important role
      in eliciting visual attention, in alerting the infant that signed communication
      is forthcoming, in assisting the infant to achieve emotional regulation, or in
      simply maintaining contact even when the deaf child has looked away from the
      partner. The data presented here represent one attempt to investigate the role of
      touch in relation to deaf infants and deaf parents, for whom it may play a
      particularly salient role. Both deaf and hearing mothers were observed in
      videotaped face-to-face interactions with their infants (also either deaf or
      hearing); maternal behavior was coded for each event during which mothers
      initiated tactile contact with the infant and was classified according to
      intensity, location on the infant's body, and type of touch (e.g., active vs.
      passive). Results of this study indicate that deaf mothers may be especially
      responsive to the tactile needs of their deaf infants, as shown by qualitative
      differences in their behavioral interactions with 6- and 9-month-olds. However,
      hearing mothers with deaf infants also appear to be incorporating more active
      forms of touch in their interactions, although they tend to rely on longer
      durations of tactile contact than do the deaf mothers.

PMID- 15454509
TI  - Parental Involvement in Deaf Children's Education Programs as a Predictor of
      Child's Language, Early Reading, and Social-Emotional Development.
AB  - This study examined the impact of school-based, teacher-rated parental
      involvement on four child outcomes: language development, early reading skills,
      and positive and negative measures of social-emotional development. The 28
      children were assessed for outcomes between 9 to 53 months post-graduation from a
      birth-to-3 early intervention (EI) program for children with hearing loss. Other
      factors included in the study were child's hearing loss, mother's education
      level, mother's current communication skills with her child, and maternal use of
      additional services beyond those offered by the early intervention program or the
      child's school program. Parental involvement in children's school-based education
      program is a significant positive predictor to early reading skills but shares
      considerable variance with maternal communication skill for this outcome. In this
      study, maternal communication skills and the child's hearing loss were the
      strongest predictors for language development. Maternal use of additional
      services was the strongest predictor to poorer social-emotional adjustment. The
      study's findings indicate that although parental involvement in their deaf
      child's school-based education program can positively contribute to academic
      performance, parental communication skill is a more significant predictor for
      positive language and academic development. Factors associated with parental
      involvement, maternal communication, and use of additional services are explored
      and suggestions are offered to enhance parental involvement and communication
      skills.

PMID- 15454510
TI  - Approaches to studying in deaf and hearing students in higher education.
AB  - We conducted a survey to compare the responses of 149 deaf students and 121
      hearing students taking the same courses to a shortened and adapted version of
      the Approaches to Studying Inventory. In general, the impact of deafness on
      approaches to studying was relatively slight, and deaf students appeared to be at
      least as capable as hearing students of engaging with the underlying meaning of
      the materials to be learned. We used factor analysis to identify eight scales,
      and differences between the two groups were statistically significant on four of
      these scales. Discriminant analysis indicated that deaf students found it more
      difficult to relate ideas on different topics and that this was more marked in
      those who preferred to communicate using sign. However, deaf students were more
      likely than hearing students to adopt a critical approach and to analyze the
      internal structure of the topics studied.

PMID- 15454511
TI  - Academic and Social Benefits of a Co-enrollment Model of Inclusive Education for
      Deaf and Hard-of-Hearing Children.
AB  - Deaf and hard-of-hearing (d/hh) students are traditionally educated within self
      contained programs at residential or special day schools, within self-contained
      or resource classrooms in public schools, or within regular education classrooms
      with support provided by an itinerant teacher. The co-enrollment model offers a
      promising alternative in which these students are educated within a regular
      education classroom composed of both d/hh and hearing students and team-taught by
      a teacher of the deaf and a regular education teacher. This article examines the
      development of one such program and the social and academic performance of the
      d/hh students within the program. Data on social interaction between d/hh and
      hearing classmates suggest that specific instructional strategies that promoted
      students' sign language development, identified d/hh students as "sign language
      specialists" and grouped d/hh and hearing students during academic activities
      resulted in increased interaction between these two groups of students. Stanford
      Achievement Test scores in the areas of reading vocabulary, reading
      comprehension, mathematical problem solving and procedures indicate that although
      d/hh students scored below the national normative hearing group, reading
      comprehension levels exceeded the national normative sample of d/hh students
      during both years two and three of the program. We discuss the challenges of
      implementing a co-enrollment program.

PMID- 15454512
TI  - On creating a workable signing environment: deaf and hearing perspectives.
AB  - This article studies teams of service providers in education and psychiatric
      services, in which a substantial number of both deaf and hearing people work
      together as colleagues. It focuses specifically on the challenges involved in
      cooperatively creating a signing work environment. Using a methodology that draws
      on the principles of ethnography, it identifies and explores the meaning
      constructions associated with signing at work, from deaf and hearing
      perspectives. Data were collected through interviews in three organizations all
      in the United Kingdom: two specialist psychiatric units for deaf adults and a
      school for deaf children. Forty-one informants participated (20 deaf, 21
      hearing). Results show that from a deaf perspective, hearing people's use of sign
      language in their presence at work is closely associated with demonstrating
      personal respect, value, and confidence, and hearing colleagues' willingness to
      sign is more significant than their fluency. From a hearing perspective, results
      demonstrate that sign language use at work is closely associated with change,
      pressure, and the questioning of professional competence. The challenges involved
      in improving deaf/hearing relations are perceived from a deaf perspective as
      largely person-centered, and from a hearing perspective as primarily language
      centered. The significance of organizational factors such as imbalances in power
      and status between deaf and hearing colleagues is explored in relation to the
      findings.

PMID- 15454513
TI  - A treatise on signed and spoken language in early 19th century deaf education in
      america.

PMID- 15454514
TI  - Principles and practices of literacy development for deaf learners: a historical
      overview.
AB  - Since the very beginning of formal approaches to deaf education, the development
      of literacy has been a priority issue. The history of educational initiatives in
      this area is entwined with the history of prevailing attitudes and practices
      toward the impact of deafness on the development of deaf children more generally.
      In particular, arguments about whether a visual input (reading) can take the
      place of a diminished auditory input and whether educators should accommodate or
      seek to ameliorate the effects of the special linguistic characteristics of deaf
      learner-readers have resulted in a wide variety of practices and perspectives.
      These varied practices and perspectives continue to have impacts on current
      educational debate and practice. This article provides a brief historical
      overview of these educational endeavors, noting the enduring questions and issues
      that remain for the field to address.

PMID- 15454515
TI  - How Do Children Who Can't Hear Learn to Read an Alphabetic Script? A Review of
      the Literature on Reading and Deafness.
AB  - I review the literature on reading and deafness, focusing on the role of three
      broad factors in acquisition and skilled reading: the method of encoding print;
      language-specific knowledge (i.e., English); and general language knowledge. I
      explore the contribution of three communication systems to reading: spoken
      language, English-based sign, and American Sign Language. Their potential
      contribution to literacy is mediated by four parameters on which they differ:
      codability, structural isomorphism, accessibility, and processibility. Finally, I
      discuss the implications for additional research as well as for education.

PMID- 15454516
TI  - Reading optimally builds on spoken language: implications for deaf readers.
AB  - Reading is not merely "language by eye." Rather, it builds fundamentally on
      primary language processes. For hearing readers, this means that spoken language
      processes, including phonological processes, are critical to high achievement in
      reading. We examine the implications of this fact for deaf readers by considering
      the relationship between language and reading and by reviewing the research on
      the use of phonology by deaf readers. The research, although mixed in its
      results, suggests that the use of phonology is associated with higher levels of
      reading skill among deaf readers. We examine related questions, including the
      additional semantic and visual strategies available to deaf readers, how some
      deaf readers gain access to the spoken structure of language, and implications
      for how to improve reading achievement.

PMID- 15454517
TI  - Children's Difficulties in Text Comprehension: Assessing Causal Issues.
AB  - In this article we consider the difficulties of children who have a specific
      reading comprehension problem. Our earlier work has shown that good and poor
      comprehenders differ, in particular, in their ability to make inferences,
      integrate information in text, understand story structure, and monitor their
      understanding. We outline some studies that illustrate the poor comprehenders'
      problems and present two studies that use a comprehension-age match design to
      explore the direction of causality between comprehension skill and other
      abilities. We also present data from the first and second stages of a
      longitudinal study, when the children were 7 to 8 and 8 to 9 years old. Multiple
      regression analyses show that a number of factors predict significant variance in
      comprehension skill even after "general ability" factors such as IQ and
      vocabulary have been taken into account. These findings suggest that, not only
      can children have comprehension problems in the absence of word recognition
      problems, but that distinctly different skills predict variance in word
      recognition and variance in comprehension. The data support the view that single
      word reading skills and the ability to build integrated text representations make
      independent contributions to overall reading ability. We discuss the implications
      of these findings for our understanding of children's problems in text
      comprehension, for deaf readers, and for remediation.

PMID- 15454518
TI  - Morphographic analysis as a word identification strategy for deaf readers.
AB  - This review of theoretical and research literature develops a rationale for
      morphographic analysis as a principal component of instruction on word
      identification for deaf students. The word identification process is
      conceptualized with regard to visually accessible morphographic components of
      text, including definition of the variables involved in morphographic analysis.
      Evidence accumulated from varied sources is presented to support this rationale
      for another approach to reading with deaf students. The conclusion outlines
      implications for instructional intervention and for future research.

PMID- 15454519
TI  - The Use of ASL to Support the Development of English and Literacy.
AB  - The purpose of this article is to review research dealing with the use of ASL in
      teaching English and literacy. I review some of the literature (and direct
      readers to additional sources) that indicates that early learning of ASL need not
      create concerns for future development of English structure, speech, or other
      cognitive skills. I also suggest ways in which ASL can contribute directly to
      developing more of the highlevel skills needed for fluent reading and writing.
      The global benefit of learning ASL as a first language is that it creates a
      standard bilingual situation in which teachers and learners can take advantage of
      one language to assist in acquiring the other and in the transfer of general
      knowledge. As part of this discussion, I compare English and ASL as natural
      languages for similarities and differences.

PMID- 15454521
TI  - Advances in literacy research and practice.

PMID- 15454520
TI  - Enhancing Science Literacy for All Students With Embedded Reading Instruction and
      Writing-to-Learn Activities.
AB  - Reading and writing in science have been frequently maligned but infrequently
      studied since the 1960s move toward hands-on science. Current interest in the
      printed-based language arts in science is supported by contemporary educational
      reforms and the realization that simply doing more hands-on activities may not
      improve meaningful learning. Students need opportunities to consolidate their
      science experiences and to contrast their understandings with the interpretations
      of the science establishment. Science literacy means that students learn about
      the "big" ideas of science and how to inform and persuade others about these
      ideas. This article attempts to sketch a substantive framework for using science
      reading and science writing with deaf students based on research and informed
      practice with hearing students.

PMID- 15454522
TI  - Constitutional hyperrecombinability and its consequences.

PMID- 15454523
TI  - Co-infection weakens selection against epistatic mutations in RNA viruses.
AB  - Co-infection may be beneficial in large populations of viruses because it permits
      sexual exchange between viruses that is useful in combating the mutational load.
      This advantage of sex should be especially substantial when mutations interact
      through negative epistasis. In contrast, co-infection may be detrimental because
      it allows virus complementation, where inferior genotypes profit from superior
      virus products available within the cell. The RNA bacteriophage phi6 features a
      genome divided into three segments. Co-infection by multiple phi6 genotypes
      produces hybrids containing reassorted mixtures of the parental segments. We
      imposed a mutational load on phi6 populations by mixing the wild-type virus with
      three single mutants, each harboring a deleterious mutation on a different one of
      the three virus segments. We then contrasted the speed at which these epistatic
      mutations were removed from virus populations in the presence and absence of co
      infection. If sex is a stronger force, we predicted that the load should be
      purged faster in the presence of co-infection. In contrast, if complementation is
      more important we hypothesized that mutations would be eliminated faster in the
      absence of co-infection. We found that the load was purged faster in the absence
      of co-infection, which suggests that the disadvantages of complementation can
      outweigh the benefits of sex, even in the presence of negative epistasis. We
      discuss our results in light of virus disease management and the evolutionary
      advantage of haploidy in biological populations.

PMID- 15454524
TI  - Analysis of Deinococcus radiodurans's transcriptional response to ionizing
      radiation and desiccation reveals novel proteins that contribute to extreme
      radioresistance.
AB  - During the first hour after a sublethal dose of ionizing radiation, 72 genes were
      upregulated threefold or higher in D. radiodurans R1. Thirty-three of these loci
      were also among a set of 73 genes expressed in R1 cultures recovering from
      desiccation. The five transcripts most highly induced in response to each stress
      are the same and encode proteins of unknown function. The genes (ddrA, ddrB,
      ddrC, ddrD, and pprA) corresponding to these transcripts were deleted, both alone
      and in all possible two-way combinations. Characterization of the mutant strains
      defines three epistasis groups that reflect different cellular responses to
      ionizing radiation-induced damage. The ddrA and ddrB gene products have
      complementary activities and inactivating both loci generates a strain that is
      more sensitive to ionizing radiation than strains in which either single gene has
      been deleted. These proteins appear to mediate efficient RecA-independent
      processes connected to ionizing radiation resistance. The pprA gene product is
      not necessary for homologous recombination during natural transformation, but
      nevertheless may participate in a RecA-dependent process during recovery from
      radiation damage. These characterizations clearly demonstrate that novel
      mechanisms significantly contribute to the ionizing radiation resistance in D.
      radiodurans.

PMID- 15454525
TI  - Does crossover interference count in Saccharomyces cerevisiae?
AB  - We previously proposed a "counting model" for meiotic crossover interference, in
      which double-strand breaks occur independently and a fixed number of
      noncrossovers occur between neighboring crossovers. Whereas in some organisms
      (group I) this simple model alone describes the crossover distribution, in other
      organisms (group II) an additional assumption--that some crossovers lack
      interference--improves the fit. Other differences exist between the groups: Group
      II needs double-strand breaks and some repair functions to achieve synapsis,
      while repair in group I generally occurs after synapsis is achieved; group II,
      but not group I, has recombination proteins Dmc1, Mnd1, and Hop2. Here we report
      experiments in msh4 mutants that are designed to test predictions of the revised
      model in a group II organism. Further, we interpret these experiments, the above
      mentioned differences between group I and II meiosis, and other data to yield the
      following proposal: Group II organisms use the repair of leptotene breaks to
      promote synapsis by generating double-Holliday-junction intermediates that lock
      homologs together (pairing pathway). The possible crossover or noncrossover
      resolution products of these structures lack interference. In contrast, for both
      group I and group II, repair during pachytene (disjunction pathway) is associated
      with interference and generates only two resolution types, whose structures
      suggest that the Holliday junctions of the repair intermediates are unligated. A
      crossover arises when such an intermediate is stabilized by a protein that
      prevents its default resolution to a noncrossover. The protein-binding pattern
      required for interference depends on clustering of sites that have received, or
      are normally about to receive, meiotic double-strand breaks.

PMID- 15454526
TI  - Gene conversion and crossing over along the 405-kb left arm of Saccharomyces
      cerevisiae chromosome VII.
AB  - Gene conversions and crossing over were analyzed along 10 intervals in a 405-kb
      region comprising nearly all of the left arm of chromosome VII in Saccharomyces
      cerevisiae. Crossover interference was detected in all intervals as measured by a
      reduced number of nonparental ditypes. We have evaluated interference between
      crossovers in adjacent intervals by methods that retain the information contained
      in tetrads as opposed to single segregants. Interference was seen between
      intervals when the distance in the region adjacent to a crossover was <
      approximately 35 cM (90 kb). At the met13 locus, which exhibits approximately 9%
      gene conversions, those gene conversions accompanied by crossing over exerted
      interference in exchanges in an adjacent interval, whereas met13 gene conversions
      without an accompanying exchange did not show interference. The pattern of
      exchanges along this chromosome arm can be represented by a counting model in
      which there are three nonexchange events between adjacent exchanges; however,
      maximum-likelihood analysis suggests that approximately 8-12% of the crossovers
      on chromosome VII arise by a separate, noninterfering mechanism.

PMID- 15454527
TI  - Heterochromatin spreading at yeast telomeres occurs in M phase.
AB  - Heterochromatin regulation of gene expression exhibits epigenetic inheritance, in
      which some feature of the structure is retained and can reseed formation in new
      cells. To understand the cell-cycle events that influence heterochromatin
      assembly and maintenance in budding yeast, we have conducted two types of
      experiments. First we have examined the kinetics of heterochromatin spreading at
      telomeres. We have constructed a strain in which the efficient silencing of a
      telomere-linked URA3 gene depends on the inducible expression of the Sir3
      silencing factor. Prior studies determined that S-phase passage was required for
      the establishment of silencing at the HM loci in yeast. We find that
      establishment of silencing in our strain occurs at a point coincident with
      mitosis and does not require S-phase passage. In addition, we find that passage
      through mitosis is sufficient to establish silencing at the HML locus in a strain
      bearing a conditional allele of SIR3. Finally, we have also assessed the
      stability of yeast heterochromatin in the absence of the cis-acting elements
      required for its establishment. We show that silencing is stable through S phase
      in the absence of silencers and therefore possesses the ability to self-propagate
      through DNA replication. However, silencing is lost in the absence of silencers
      during progression through M phase. These experiments point to crucial events in
      mitosis influencing the assembly and persistence of heterochromatin.

PMID- 15454528
TI  - Abortive transposition by a group II intron in yeast mitochondria.
AB  - Group II intron homing in yeast mitochondria is initiated at active target sites
      by activities of intron-encoded ribonucleoprotein (RNP) particles, but is
      completed by competing recombination and repair mechanisms. Intron aI1 transposes
      in haploid cells at low frequency to target sites in mtDNA that resemble the exon
      1-exon 2 (E1/E2) homing site. This study investigates a system in which aI1 can
      transpose in crosses (i.e., in trans). Surprisingly, replacing an inefficient
      transposition site with an active E1/E2 site supports <1% transposition of aI1.
      Instead, the ectopic site was mainly converted to the related sequence in donor
      mtDNA in a process we call "abortive transposition." Efficient abortive events
      depend on sequences in both E1 and E2, suggesting that most events result from
      cleavage of the target site by the intron RNP particles, gapping, and
      recombinational repair using homologous sequences in donor mtDNA. A donor strain
      that lacks RT activity carries out little abortive transposition, indicating that
      cDNA synthesis actually promotes abortive events. We also infer that some
      intermediates abort by ejecting the intron RNA from the DNA target by forward
      splicing. These experiments provide new insights to group II intron transposition
      and homing mechanisms in yeast mitochondria.

PMID- 15454529
TI  - Increase in Ty1 cDNA recombination in yeast sir4 mutant strains at high
      temperature.
AB  - Transposition of the Ty1 element of the yeast Saccharomyces cerevisiae is
      temperature sensitive. We have identified a null allele of the silent information
      regulator gene SIR4 as a host mutant that allows for transposition at high
      temperature. We show that the apparent increase in transposition activity in sir4
      mutant strains at high temperature is dependent on the RAD52 gene and is thus
      likely resulting from an increase in Ty1 cDNA recombination, rather than in IN
      mediated integration. General cellular recombination is not increased at high
      temperature, suggesting that the increase in recombination at high temperature in
      sir4 mutants is specific for Ty1 cDNA. Additionally, this high-temperature Ty1
      recombination was found to be dependent on functional Sir2p and Sir3p. We
      speculate that the increase in recombination seen in sir4 mutants at high
      temperature may be due to changes in chromatin structure or Ty1 interactions with
      chromosomal structures resulting in higher recombination rates.

PMID- 15454530
TI  - Exo1 and Rad24 differentially regulate generation of ssDNA at telomeres of
      Saccharomyces cerevisiae cdc13-1 mutants.
AB  - Cell cycle arrest in response to DNA damage depends upon coordinated interactions
      between DNA repair and checkpoint pathways. Here we examine the role of DNA
      repair and checkpoint genes in responding to unprotected telomeres in budding
      yeast cdc13-1 mutants. We show that Exo1 is unique among the repair genes tested
      because like Rad9 and Rad24 checkpoint proteins, Exo1 inhibits the growth of
      cdc13-1 mutants at the semipermissive temperatures. In contrast Mre11, Rad50,
      Xrs2, and Rad27 contribute to the vitality of cdc13-1 strains grown at permissive
      temperatures, while Din7, Msh2, Nuc1, Rad2, Rad52, and Yen1 show no effect. Exo1
      is not required for cell cycle arrest of cdc13-1 mutants at 36 degrees but is
      required to maintain arrest. Exo1 affects but is not essential for the production
      of ssDNA in subtelomeric Y' repeats of cdc13-1 mutants. However, Exo1 is critical
      for generating ssDNA in subtelomeric X repeats and internal single-copy
      sequences. Surprisingly, and in contrast to Rad24, Exo1 is not essential to
      generate ssDNA in X or single-copy sequences in cdc13-1 rad9Delta mutants. We
      conclude that Rad24 and Exo1 regulate nucleases with different properties at
      uncapped telomeres and propose a model to explain our findings.

PMID- 15454531
TI  - Division of labor among the yeast Sol proteins implicated in tRNA nuclear export
      and carbohydrate metabolism.
AB  - SOL1, the founding member of the S. cerevisiae SOL family, was previously
      identified as a multi-copy suppressor of the los1 defect in tRNA-mediated
      nonsense suppression. Here we report that the four-member SOL family is not
      essential and that individual family members appear to have distinct functions.
      SOL1-SOL4 are homologous to genes encoding 6-phosphogluconolactonase (6Pgl)
      involved in the pentose phosphate pathway. Both Sol3p and Sol4p affect this
      activity. However, Sol4p does not act as a los1 multi-copy suppressor. In
      contrast, neither Sol1p nor Sol2p, both of which correct the los1 defect in
      nonsense suppression, possess detectable 6Pgl activity. Rather, Sol1p and Sol2p
      appear to function in tRNA nuclear export as sol1 and sol2 mutants possess
      elevated levels of nuclear tRNA. Members of the Sol protein family appear to have
      different subcellular distributions. Thus, Sol3p and Sol4p likely function in
      carbohydrate metabolism, while Sol1p and Sol2p appear to have roles in tRNA
      function and nuclear export, thereby defining an unusual protein family whose
      individual members are biochemically distinct and spatially dispersed.

PMID- 15454532
TI  - Functional distinction between Cln1p and Cln2p cyclins in the control of the
      Saccharomyces cerevisiae mitotic cycle.
AB  - Cln1p and Cln2p are considered as equivalent cyclins on the basis of sequence
      homology, regulation, and functional studies. Here we describe a functional
      distinction between the Cln1p and Cln2p cyclins in the control of the G1/S
      transition. Inactivation of CLN2, but not of CLN1, leads to a larger-than-normal
      cell size, whereas overexpression of CLN2, but not of CLN1, results in smaller
      than-normal cells. Furthermore, mild ectopic expression of CLN2, but not of CLN1,
      suppresses the lethality of swi4swi6 and cdc28 mutant strains. In the absence of
      Cln1p, the kinetics of budding, initiation of DNA replication, and activation of
      the Start-transcription program are not affected; by contrast, loss of Cln2p
      causes a delay in bud emergence. A primary role for Cln2p but not for Cln1p in
      budding is reinforced by the observation that only the cln2 mutation is synthetic
      lethal with a cdc42 mutation, and only the cln2 mutant strain is hypersensitive
      to latrunculin B. In addition, we found that Cln1p showed a more prominent
      nuclear staining than Cln2p. Finally, chimeric proteins composed of Cln1p and
      Cln2p revealed that Cln2p integrity is required for its functional specificity.

PMID- 15454533
TI  - Shared forces of sex chromosome evolution in haploid-mating and diploid-mating
      organisms: Microbotryum violaceum and other model organisms.
AB  - It is usually posited that the most important factors contributing to sex
      chromosome evolution in diploids are the suppression of meiotic recombination and
      the asymmetry that results from one chromosome (the Y) being permanently
      heterozygous and the other (the X) being homozygous in half of the individuals
      involved in mating. To distinguish between the roles of these two factors, it
      would be valuable to compare sex chromosomes in diploid-mating organisms and
      organisms where mating compatibility is determined in the haploid stage. In this
      latter group, no such asymmetry occurs because the sex chromosomes are equally
      heterozygous. Here we show in the fungus Microbotryum violaceum that the
      chromosomes carrying the mating-type locus, and thus determining haploid-mating
      compatibility, are rich in transposable elements, dimorphic in size, and carry
      unequal densities of functional genes. Through analysis of available complete
      genomes, we also show that M. violaceum is, remarkably, more similar to humans
      and mice than to yeast, nematodes, or fruit flies with regard to the differential
      accumulation of transposable elements in the chromosomes determining mating
      compatibility vs. the autosomes. We conclude that restricted recombination,
      rather than asymmetrical sheltering, hemizygosity, or dosage compensation, is
      sufficient to account for the common sex chromosome characteristics.

PMID- 15454534
TI  - GLD-3 and control of the mitosis/meiosis decision in the germline of
      Caenorhabditis elegans.
AB  - Germ cells can divide mitotically to replenish germline tissue or meiotically to
      produce gametes. In this article, we report that GLD-3, a Caenorhabditis elegans
      Bicaudal-C homolog, promotes the transition from mitosis to meiosis together with
      the GLD-2 poly(A) polymerase. GLD-3 binds GLD-2 via a small N-terminal region
      present in both GLD-3S and GLD-3L isoforms, and GLD-2 and GLD-3 can be co
      immunoprecipitated from worm extracts. The FBF repressor binds specifically to
      elements in the gld-3S 3'-UTR, and FBF regulates gld-3 expression. Furthermore,
      FBF acts largely upstream of gld-3 in the mitosis/meiosis decision. By contrast,
      GLD-3 acts upstream of FBF in the sperm/oocyte decision, and GLD-3 protein can
      antagonize FBF binding to RNA regulatory elements. To address the relative
      importance of these two regulatory mechanisms in the mitosis/meiosis and
      sperm/oocyte decisions, we isolated a deletion mutant, gld-3(q741), that removes
      the FBF-binding site from GLD-3L, but leaves the GLD-2-binding site intact.
      Animals homozygous for gld-3(q741) enter meiosis, but are feminized. Therefore,
      GLD-3 promotes meiosis primarily via its interaction with GLD-2, and it promotes
      spermatogenesis primarily via its interaction with FBF.

PMID- 15454535
TI  - A screen for genes that interact with the Drosophila pair-rule segmentation gene
      fushi tarazu.
AB  - The pair-rule gene fushi tarazu (ftz) of Drosophila is expressed at the
      blastoderm stage in seven stripes that serve to define the even-numbered
      parasegments. ftz encodes a DNA-binding homeodomain protein and is known to
      regulate genes of the segment polarity, homeotic, and pair-rule classes. Despite
      intensive analysis in a number of laboratories, how ftz is regulated and how it
      controls its targets are still poorly understood. To help understand these
      processes, we conducted a screen to identify dominant mutations that enhance the
      lethality of a ftz temperature-sensitive mutant. Twenty-six enhancers were
      isolated, which define 21 genes. All but one of the mutations recovered show a
      maternal effect in their interaction with ftz. Three of the enhancers proved to
      be alleles of the known ftz protein cofactor gene ftz-f1, demonstrating the
      efficacy of the screen. Four enhancers are alleles of Atrophin (Atro), the
      Drosophila homolog of the human gene responsible for the neurodegenerative
      disease dentatorubral-pallidoluysian atrophy. Embryos from Atro mutant germ-line
      mothers lack the even-numbered (ftz-dependent) engrailed stripes and show strong
      ftz-like segmentation defects. These defects likely result from a reduction in
      Even-skipped (Eve) repression ability, as Atro has been shown to function as a
      corepressor for Eve. In this study, we present evidence that Atro is also a
      member of the trithorax group (trxG) of Hox gene regulators. Atro appears to be
      particularly closely related in function to the trxG gene osa, which encodes a
      component of the brahma chromatin remodeling complex. One additional gene was
      identified that causes pair-rule segmentation defects in embryos from homozygous
      mutant germ-line mothers. The single allele of this gene, called bek, also causes
      nuclear abnormalities similar to those caused by alleles of the Trithorax-like
      gene, which encodes the GAGA factor.

PMID- 15454536
TI  - Virulence, multiple infections and regulation of symbiotic population in the
      Wolbachia-Asobara tabida symbiosis.
AB  - The density and regulation of microbial populations are important factors in the
      success of symbiotic associations. High bacterial density may improve
      transmission to the next generation, but excessive replication could turn out to
      be costly to the host and result in higher virulence. Moreover, differences in
      virulence may also depend on the diversity of symbionts. Using the maternally
      transmitted symbiont Wolbachia, we investigated how bacterial density and
      diversity are regulated and influence virulence in host insects subject to
      multiple infection. The model we used was the wasp Asobara tabida that naturally
      harbors three different Wolbachia strains, of which two are facultative and
      induce cytoplasmic incompatibility, whereas the third is necessary for the host
      to achieve oogenesis. Using insect lines infected with different subsets of
      Wolbachia strains, we show that: (i) some traits of A. tabida are negatively
      affected by Wolbachia; (ii) the physiological cost increases with the number of
      co-infecting strains, which also corresponds to an increase in the total
      bacterial density; and (iii) the densities of the two facultative Wolbachia
      strains are independent of one another, whereas the obligatory strain is less
      abundant when it is alone, suggesting that there is some positive interaction
      with the other strains.

PMID- 15454537
TI  - stall-mediated extrinsic control of ovarian follicle formation in Drosophila.
AB  - Complex patterns of morphogenesis require intricate coordination of multiple,
      regulatory processes that control cellular identities, shapes, and behaviors,
      both locally and over vast distances in the developing organism or tissue.
      Studying Drosophila oogenesis as a model for tissue morphogenesis, we have
      discovered extraovarian regulation of follicle formation. Clonal analysis and
      ovary transplantation have demonstrated that long-range control of follicle
      individualization requires stall gene function in cells outside of the ovary.
      Although tissue nonautonomous regulation has been shown to govern follicle
      maturation and survival, this is the first report of an extraovarian pathway
      involved in normal follicle formation.

PMID- 15454539
TI  - An AFLP-based interspecific linkage map of sympatric, hybridizing Colias
      butterflies.
AB  - Colias eurytheme and C. philodice are sister species with broad sympatry in North
      America. They hybridize frequently and likely share a significant portion of
      their genomes through introgression. Both taxa have been ecologically well
      characterized and exploited to address a broad spectrum of evolutionary issues.
      Using AFLP markers, we constructed the first linkage map of Colias butterflies.
      The map is composed of 452 markers spanning 2541.7 cM distributed over 51 linkage
      groups (40 major groups and 11 small groups with 2-4 markers). Statistical tests
      indicate that these AFLP markers tend to cluster over the map, with the
      coefficient of variation of interval sizes being 1.236 (95% C.I. is 1.234-1.240).
      This nonrandom marker distribution can account for the nonequivalence between the
      number of linkage groups and the actual haploid chromosome number (N = 31). This
      study presents the initial step for further marker-assisted research on Colias
      butterflies, including QTL and introgression analyses. Further investigation of
      the genomes will help us understand better the roles of introgression and natural
      selection in the evolution of hybridizing species and devise more appropriate
      strategies to control these pests.

PMID- 15454538
TI  - SNR1 (INI1/SNF5) mediates important cell growth functions of the Drosophila
      Brahma (SWI/SNF) chromatin remodeling complex.
AB  - SNR1 is an essential subunit of the Drosophila Brahma (Brm) ATP-dependent
      chromatin remodeling complex, with counterparts in yeast (SNF5) and mammals
      (INI1). Increased cell growth and wing patterning defects are associated with a
      conditional snr1 mutant, while loss of INI1 function is directly linked with
      aggressive cancers, suggesting important roles in development and growth control.
      The Brm complex is known to function during G1 phase, where it appears to assist
      in restricting entry into S phase. In Drosophila, the activity of DmcycE/CDK2 is
      rate limiting for entry into S phase and we previously found that the Brm complex
      can suppress a reduced growth phenotype associated with a hypomorphic DmcycE
      mutant. Our results reveal that SNR1 helps mediate associations between the Brm
      complex and DmcycE/CDK2 both in vitro and in vivo. Further, disrupting snr1
      function suppressed DmcycEJP phenotypes, and increased cell growth defects
      associated with the conditional snr1E1 mutant were suppressed by reducing DmcycE
      levels. While the snr1E1-dependent increased cell growth did not appear to be
      directly associated with altered expression of G1 or G2 cyclins, transcription of
      the G2-M regulator string/cdc25 was reduced. Thus, in addition to important
      functions of the Brm complex in G1-S control, the complex also appears to be
      important for transcription of genes required for cell cycle progression.

PMID- 15454540
TI  - A genetic screen for dominant modifiers of a cyclin E hypomorphic mutation
      identifies novel regulators of S-phase entry in Drosophila.
AB  - Cyclin E together with its kinase partner Cdk2 is a critical regulator of entry
      into S phase. To identify novel genes that regulate the G1- to S-phase transition
      within a whole animal we made use of a hypomorphic cyclin E mutation, DmcycEJP,
      which results in a rough eye phenotype. We screened the X and third chromosome
      deficiencies, tested candidate genes, and carried out a genetic screen of 55,000
      EMS or X-ray-mutagenized flies for second or third chromosome mutations that
      dominantly modified the DmcycEJP rough eye phenotype. We have focused on the
      DmcycEJP suppressors, S(DmcycEJP), to identify novel negative regulators of S
      phase entry. There are 18 suppressor gene groups with more than one allele and
      several genes that are represented by only a single allele. All S(DmcycEJP)
      tested suppress the DmcycEJP rough eye phenotype by increasing the number of S
      phases in the postmorphogenetic furrow S-phase band. By testing candidates we
      have identified several modifier genes from the mutagenic screen as well as from
      the deficiency screen. DmcycEJP suppressor genes fall into the classes of: (1)
      chromatin remodeling or transcription factors; (2) signaling pathways; and (3)
      cytoskeletal, (4) cell adhesion, and (5) cytoarchitectural tumor suppressors. The
      cytoarchitectural tumor suppressors include scribble, lethal-2-giant-larvae
      (lgl), and discs-large (dlg), loss of function of which leads to neoplastic
      tumors and disruption of apical-basal cell polarity. We further explored the
      genetic interactions of scribble with S(DmcycEJP) genes and show that hypomorphic
      scribble mutants exhibit genetic interactions with lgl, scab (alphaPS3-integrin-
      cell adhesion), phyllopod (signaling), dEB1 (microtubule-binding protein-
      cytoskeletal), and moira (chromatin remodeling). These interactions of the
      cytoarchitectural suppressor gene, scribble, with cell adhesion, signaling,
      cytoskeletal, and chromatin remodeling genes, suggest that these genes may act in
      a common pathway to negatively regulate cyclin E or S-phase entry.

PMID- 15454541
TI  - Duplicative and conservative transpositions of larval serum protein 1 genes in
      the genus Drosophila.
AB  - Interspecific comparative molecular analyses of transposed genes and their
      flanking regions can help to elucidate the time, direction, and mechanism of gene
      transposition. In the Drosophila melanogaster genome, three Larval serum protein
      1 (Lsp1) genes (alpha, beta and gamma) are present and each of them is located on
      a different chromosome, suggesting multiple transposition events. We have
      characterized the molecular organization of Lsp1 genes in D. buzzatii, a species
      of the Drosophila subgenus and in D. pseudoobscura, a species of the Sophophora
      subgenus. Our results show that only two Lsp1 genes (beta and gamma) exist in
      these two species. The same chromosomal localization and genomic organization,
      different from that of D. melanogaster, is found in both species for the Lsp1beta
      and Lsp1gamma genes. Overall, at least two duplicative and two conservative
      transpositions are necessary to explain the present chromosomal distribution of
      Lsp1 genes in the three Drosophila species. Clear evidence for implication of
      snRNA genes in the transposition of Lsp1beta in Drosophila has been found. We
      suggest that an ectopic exchange between highly similar snRNA sequences was
      responsible for the transposition of this gene. We have also identified the
      putative cis-acting regulatory regions of these genes, which seemingly transposed
      along with the coding sequences.

PMID- 15454542
TI  - Identification of a locus under complex positive selection in Drosophila simulans
      by haplotype mapping and composite-likelihood estimation.
AB  - The recent action of positive selection is expected to influence patterns of
      intraspecific DNA sequence variation in chromosomal regions linked to the
      selected locus. These effects include decreased polymorphism, increased linkage
      disequilibrium, and an increased frequency of derived variants. These effects are
      all expected to dissipate with distance from the selected locus due to
      recombination. Therefore, in regions of high recombination, it should be possible
      to localize a target of selection to a relatively small interval. Previously
      described patterns of intraspecific variation in three tandemly arranged, testes
      expressed genes (janusA, janusB, and ocnus) in Drosophila simulans included all
      three of these features. Here we expand the original sample and also survey
      nucleotide polymorphism at three neighboring loci. On the basis of recombination
      events between derived and ancestral alleles, we localize the target of selection
      to a 1.5-kb region surrounding janusB. A composite-likelihood-ratio test based on
      the spatial distribution and frequency of derived polymorphic variants
      corroborates this result and provides an estimate of the strength of selection.
      However, the data are difficult to reconcile with the simplest model of positive
      selection, whereas a new composite-likelihood method suggests that the data are
      better described by a model in which the selected allele has not yet gone to
      fixation.

PMID- 15454543
TI  - Dose-sensitive autosomal modifiers identify candidate genes for tissue autonomous
      and tissue nonautonomous regulation by the Drosophila nuclear zinc-finger
      protein, hindsight.
AB  - The nuclear zinc-finger protein encoded by the hindsight (hnt) locus regulates
      several cellular processes in Drosophila epithelia, including the Jun N-terminal
      kinase (JNK) signaling pathway and actin polymerization. Defects in these
      molecular pathways may underlie the abnormal cellular interactions, loss of
      epithelial integrity, and apoptosis that occurs in hnt mutants, in turn causing
      failure of morphogenetic processes such as germ band retraction and dorsal
      closure in the embryo. To define the genetic pathways regulated by hnt, 124
      deficiencies on the second and third chromosomes and 14 duplications on the
      second chromosome were assayed for dose-sensitive modification of a temperature
      sensitive rough eye phenotype caused by the viable allele, hntpeb; 29 interacting
      regions were identified. Subsequently, 438 P-element-induced lethal mutations
      mapping to these regions and 12 candidate genes were tested for genetic
      interaction, leading to identification of 63 dominant modifier loci. A subset of
      the identified mutants also dominantly modify hnt308-induced embryonic lethality
      and thus represent general rather than tissue-specific interactors. General
      interactors include loci encoding transcription factors, actin-binding proteins,
      signal transduction proteins, and components of the extracellular matrix.
      Expression of several interactors was assessed in hnt mutant tissue. Five genes-
      apontic (apt), Delta (Dl), decapentaplegic (dpp), karst (kst), and puckered (puc)
      -are regulated tissue autonomously and, thus, may be direct transcriptional
      targets of HNT. Three of these genes--apt, Dl, and dpp--are also regulated
      nonautonomously in adjacent non-HNT-expressing tissues. The expression of several
      additional interactors--viking (vkg), Cg25, and laminin-alpha (LanA)-is affected
      only in a nonautonomous manner.

PMID- 15454544
TI  - Quantitative trait loci affecting life span in replicated populations of
      Drosophila melanogaster. I. Composite interval mapping.
AB  - Composite interval mapping was used to identify life-span QTL in F2 progeny of
      three crosses between different pairs of inbred lines. Each inbred line was
      derived from a different outbred population that had undergone long-term
      selection for either long or short life span. Microsatellite loci were used as
      genetic markers, and confidence intervals for QTL location were estimated by
      bootstrapping. A minimum of 10 QTL were detected, nine of which were located on
      the two major autosomes. Five QTL were present in at least two crosses and five
      were present in both sexes. Observation of the same QTL in more than one cross
      was consistent with the hypothesis that genetic variation for life span is
      maintained by balancing selection. For all QTL except one, allelic effects were
      in the direction predicted on the basis of outbred source population. Alleles
      that conferred longer life were always at least partially dominant.

PMID- 15454545
TI  - Quantitative trait loci affecting life span in replicated populations of
      Drosophila melanogaster. II. Response to selection.
AB  - Three selection experiments were used to identify chromosome regions that contain
      QTL affecting late-life and early-life fitness in Drosophila melanogaster. The
      selection experiments were initiated by crossing pairs of inbred lines that had
      been derived from outbred laboratory populations that had different mean life
      spans. QTL regions were located by association with microsatellite markers that
      showed significant selection responses. Regions between recombination map
      positions 54 and 81 on chromosome 2, between 0 and 30 on chromosome 3, and near
      locations 49 and 81 on chromosome 3 had the strongest support as locations of
      life-span QTL. There was good general agreement between the life-span QTL regions
      that were identified by selection and those that were identified in a companion
      recombination mapping experiment that used the same fly stocks. Many marker loci
      responded in opposite directions to selection for late- and early-life fitness,
      indicating negative genetic correlations or trade-offs between those traits.
      Indirect evidence suggested that some negative genetic correlations were due to
      antagonistic pleiotropy.

PMID- 15454546
TI  - Identification and characterization of genes involved in embryonic crystal cell
      formation during Drosophila hematopoiesis.
AB  - Parallels between vertebrate and Drosophila hematopoiesis add to the value of
      flies as a model organism to gain insights into blood development. The Drosophila
      hematopoietic system is composed of at least three classes of terminally
      differentiated blood cells: plasmatocytes, crystal cells, and lamellocytes.
      Recent studies have identified transcriptional and signaling pathways in
      Drosophila involving proteins similar to those seen in human blood development.
      To identify additional genes involved in Drosophila hematopoiesis, we have
      conducted a P-element-based genetic screen to isolate mutations that affect
      embryonic crystal cell development. Using a marker of terminally differentiated
      crystal cells, we screened 1040 P-element-lethal lines located on the second and
      third chromosomes and identified 44 individual lines that affect crystal cell
      development. Identifying novel genes and pathways involved in Drosophila
      hematopoiesis is likely to provide further insights into mammalian hematopoietic
      development and disorders.

PMID- 15454547
TI  - The genetic basis of male fertility in relation to haplodiploid reproduction in
      Leptopilina clavipes (Hymenoptera: Figitidae).
AB  - Traits under relaxed selection are expected to become reduced or disappear
      completely, a process called vestigialization. In parthenogenetic populations,
      traits historically involved in sexual reproduction are no longer under selection
      and potentially subject to such reduction. In Leptopilina clavipes, thelytokous
      (parthenogenetic) populations are infected by Wolbachia bacteria. Arrhenotokous
      populations do not harbor Wolbachia. When antibiotics are applied to infected
      females, they are cured from their infection and males arise. Such males are
      capable of producing offspring with uninfected females, but with lower
      fertilization success than sexual males. This can be attributed to the lack of
      selection on male fertility in thelytokous lines. In this study we used this
      variation in L. clavipes male fertility to determine the genetic basis of this
      trait. Males from cured thelytokous populations were crossed to females from
      uninfected populations. Using AFLP markers, a genetic linkage map was generated,
      consisting of five linkage groups and spanning a total distance of 219.9 cM. A
      single QTL of large effect (explaining 46.5% of the phenotypic variance) was
      identified for male fertility, which we call male fertility factor (mff). We
      discuss possible mechanisms underlying the effect of mff, as well as mechanisms
      involved in vestigialization of traits involved in sexual reproduction.

PMID- 15454548
TI  - Linkage maps of microsatellite DNA markers for the Pacific oyster Crassostrea
      gigas.
AB  - We constructed male and female consensus linkage maps for the Pacific oyster
      Crassostrea gigas, using a total of 102 microsatellite DNA markers typed in 11
      day-old larvae from three families. We identified 11 and 12 linkage groups in the
      male and female consensus maps, respectively. Alignment of these separate maps,
      however, suggests 10 linkage groups, which agrees with the haploid chromosome
      number. The male linkage map comprises 88 loci and spans 616.1 cM, while the
      female map comprises 86 loci and spans 770.5 cM. The male and the female maps
      share 74 loci; 2 markers remain unlinked. The estimated coverages for the
      consensus linkage maps are 79% for the male and 70-75% for the female, on the
      basis of two estimates of genome length. Ninety-five percent of the genome is
      expected to lie within 16 and 21 cM of markers on the male and female maps,
      respectively, while 95% of simulated minimum distances to the male and female
      maps are within 10.1 and 13.6 cM, respectively. Females have significantly more
      recombination than males, across 118 pairs of linked markers in common to the
      parents of the three families. Significant differences in recombination and
      orders of markers are also evident among same-sex parents of different families
      as well as sibling parents of opposite sex. These observations suggest that
      polymorphism for chromosomal rearrangements may exist in natural populations,
      which could have profound implications for interpreting the evolutionary genetics
      of the oyster. These are the first linkage maps for a bivalve mollusc that use
      microsatellite DNA markers, which should enable them to be transferred to other
      families and to be useful for further genetic analyses such as QTL mapping.

PMID- 15454549
TI  - A microsatellite genetic linkage map for Xiphophorus.
AB  - Interspecies hybrids between distinct species of the genus Xiphophorus are often
      used in varied research investigations to identify genomic regions associated
      with the inheritance of complex traits. There are 24 described Xiphophorus
      species and a greater number of pedigreed strains; thus, the number of potential
      interspecies hybrid cross combinations is quite large. Previously, select
      Xiphophorus experimental crosses have been shown to exhibit differing
      characteristics between parental species and among the hybrid fishes derived from
      crossing them, such as widely differing susceptibilities to chemical or physical
      agents. For instance, genomic regions harboring tumor suppressor and oncogenes
      have been identified via linkage association of these loci with a small set of
      established genetic markers. The power of this experimental strategy is related
      to the number of genetic markers available in the Xiphophorus interspecies cross
      of interest. Thus, we have undertaken the task of expanding the suite of easily
      scored markers by characterization of Xiphophorus microsatellite sequences. Using
      a cross between Xiphophorus maculatus and X. andersi, we report a linkage map
      predominantly composed of microsatellite markers. All 24 acrocentric chromosome
      sets of Xiphophorus are represented in the assembled linkage map with an average
      intergenomic distance of 7.5 cM. Since both male and female F1 hybrids were used
      to produce backcross progeny, these recombination rates were compared between
      "male" and "female" maps. Although several genomic regions exhibit differences in
      map length, male- and female-derived maps are similar. Thus Xiphophorus, in
      contrast to zebrafish, Danio rerio, and several other vertebrate species, does
      not show sex-specific differences in recombination. The microsatellite markers we
      report can be easily adapted to any Xiphophorus interspecies and some
      intraspecies crosses, and thus provide a means to directly compare results
      derived from independent experiments.

PMID- 15454550
TI  - Gene expression intensity shapes evolutionary rates of the proteins encoded by
      the vertebrate genome.
AB  - Natural selection leaves its footprints on protein-coding sequences by modulating
      their silent and replacement evolutionary rates. In highly expressed genes in
      invertebrates, these footprints are seen in the higher codon usage bias and lower
      synonymous divergence. In mammals, the highly expressed genes have a shorter gene
      length in the genome and the breadth of expression is known to constrain the rate
      of protein evolution. Here we have examined how the rates of evolution of
      proteins encoded by the vertebrate genomes are modulated by the amount
      (intensity) of gene expression. To understand how natural selection operates on
      proteins that appear to have arisen in earlier and later phases of animal
      evolution, we have contrasted patterns of mouse proteins that have homologs in
      invertebrate and protist genomes (Precambrian genes) with those that do not have
      such detectable homologs (vertebrate-specific genes). We find that the intensity
      of gene expression relates inversely to the rate of protein sequence evolution on
      a genomic scale. The most highly expressed genes actually show the lowest total
      number of substitutions per polypeptide, consistent with cumulative effects of
      purifying selection on individual amino acid replacements. Precambrian genes
      exhibit a more pronounced difference in protein evolutionary rates (up to three
      times) between the genes with high and low expression levels as compared to the
      vertebrate-specific genes, which appears to be due to the narrower breadth of
      expression of the vertebrate-specific genes. These results provide insights into
      the differential relationship and effect of the increasing complexity of animal
      body form on evolutionary rates of proteins.

PMID- 15454551
TI  - Microsatellite mutation models: insights from a comparison of humans and
      chimpanzees.
AB  - Using genomic data from homologous microsatellite loci of pure AC repeats in
      humans and chimpanzees, several models of microsatellite evolution are tested and
      compared using likelihood-ratio tests and the Akaike information criterion. A
      proportional-rate, linear-biased, one-phase model emerges as the best model. A
      focal length toward which the mutational and/or substitutional process is
      linearly biased is a crucial feature of microsatellite evolution. We find that
      two-phase models do not lead to a significantly better fit than their one-phase
      counterparts. The performance of models based on the fit of their stationary
      distributions to the empirical distribution of microsatellite lengths in the
      human genome is consistent with that based on the human-chimp comparison.
      Microsatellites interrupted by even a single point mutation exhibit a twofold
      decrease in their mutation rate when compared to pure AC repeats. In general,
      models that allow chimps to have a larger per-repeat unit slippage rate and/or a
      shorter focal length compared to humans give a better fit to the human-chimp data
      as well as the human genomic data.

PMID- 15454552
TI  - Interactions between imprinting effects in the mouse.
AB  - Mice with uniparental partial or complete disomies for any one of 11 identified
      chromosomes show abnormal phenotypes. The abnormalities, or imprinting effects,
      can be attributable to an incorrect dosage of maternal or paternal copies of
      imprinted gene(s) located within the regions involved. Here we show that
      combinations of partial disomies may result in interactions between imprinting
      effects that seemingly independently affect fetal and/or placental growth in
      different ways or modify neonatal and postnatal imprinting effects. Candidate
      genes within the regions have been identified. The findings are generally in
      accord with the "conflict hypothesis" for the evolution of genomic imprinting but
      do not clearly demonstrate common growth axes within which imprinted genes may
      interact. Instead, it would seem that any gene that represses or limits
      embryonic/fetal growth to the advantage of the mother--by any developmental means
      -will have been subject to evolutionary selection for paternal allele repression.
      Likewise, any gene that favors embryonic/fetal development at consequent cost to
      the mother--by any developmental means--will have faced selection for maternal
      allele repression. The classical Igf2-Igf2r axis may therefore be unique. The
      findings involve reinterpretation of older imprinting data and consequently
      revision of the mouse imprinting map.

PMID- 15454553
TI  - Radiation hybrid mapping of the species cytoplasm-specific (scsae) gene in wheat.
AB  - Radiation hybrid (RH) mapping is based on radiation-induced chromosome breakage
      and analysis of chromosome segment retention or loss using molecular markers. In
      durum wheat (Triticum turgidum L., AABB), an alloplasmic durum line [(lo) durum]
      has been identified with chromosome 1D of T. aestivum L. (AABBDD) carrying the
      species cytoplasm-specific (scsae) gene. The chromosome 1D of this line
      segregates as a whole without recombination, precluding the use of conventional
      genome mapping. A radiation hybrid mapping population was developed from a
      hemizygous (lo) scsae--line using 35 krad gamma rays. The analysis of 87
      individuals of this population with 39 molecular markers mapped on chromosome 1D
      revealed 88 radiation-induced breaks in this chromosome. This number of
      chromosome 1D breaks is eight times higher than the number of previously
      identified breaks and should result in a 10-fold increase in mapping resolution
      compared to what was previously possible. The analysis of molecular marker
      retention in our radiation hybrid mapping panel allowed the localization of scsae
      and 8 linked markers on the long arm of chromosome 1D. This constitutes the first
      report of using RH mapping to localize a gene in wheat and illustrates that this
      approach is feasible in a species with a large complex genome.

PMID- 15454554
TI  - Population genetic evidence for rapid changes in intraspecific diversity and
      allelic cycling of a specialist defense gene in Zea.
AB  - Two patterns of plant defense gene evolution are emerging from molecular
      population genetic surveys. One is that specialist defenses experience stronger
      selection than generalist defenses. The second is that specialist defenses are
      more likely to be subject to balancing selection, i.e., evolve in a manner
      consistent with balanced-polymorphism or trench-warfare models of host-parasite
      coevolution. Because most of the data of specialist defenses come from
      Arabidopsis thaliana, we examined the genetic diversity and evolutionary history
      of three defense genes in two outcrossing species, the autotetraploid Zea
      perennis and its most closely related extant relative the diploid Z.
      diploperennis. Intraspecific diversity at two generalist defenses, the protease
      inhibitors wip1 and mpi, were consistent with a neutral model. Like previously
      studied genes in these taxa, wip1 and mpi harbored similar levels of diversity in
      Z. diploperennis and Z. perennis. In contrast, the specialist defense hm2 showed
      strong although distinctly different departures from a neutral model in the two
      species. Z. diploperennis appears to have experienced a strong and recent
      selective sweep. Using a rejection-sampling coalescent method, we estimate the
      strength of selection on Z. diploperennis hm2 to be approximately 3.0%, which is
      approximately equal to the strength of selection on tb1 during maize
      domestication. Z. perennis hm2 harbors three highly diverged alleles, two of
      which are found at high frequency. The distinctly different patterns of diversity
      may be due to differences in the phase of host-parasite coevolutionary cycles,
      although higher hm2 diversity in Z. perennis may also reflect reduced efficacy of
      selection in the autotetraploid relative to its diploid relative.

PMID- 15454555
TI  - Linkage disequilibrium mapping of yield and yield stability in modern spring
      barley cultivars.
AB  - Associations between markers and complex quantitative traits were investigated in
      a collection of 146 modern two-row spring barley cultivars, representing the
      current commercial germ plasm in Europe. Using 236 AFLP markers, associations
      between markers were found for markers as far apart as 10 cM. Subsequently, for
      the 146 cultivars the complex traits mean yield, adaptability (Finlay-Wilkinson
      slope), and stability (deviations from regression) were estimated from the
      analysis of variety trial data. Regression of those traits on individual marker
      data disclosed marker-trait associations for mean yield and yield stability.
      Support for identified associations was obtained from association profiles, i.e.,
      from plots of P-values against chromosome positions. In addition, many of the
      associated markers were located in regions where earlier QTL were found for yield
      and yield components. To study the oligogenic genetic base of the traits in more
      detail, multiple linear regression of the traits on markers was carried out,
      using stepwise selection. By this procedure, 18-20 markers that accounted for 40
      58% of the variation were selected. Our results indicate that association mapping
      approaches can be a viable alternative to classical QTL approaches based on
      crosses between inbred lines, especially for complex traits with costly
      measurements.

PMID- 15454556
TI  - Comparative mapping in the Pinaceae.
AB  - A comparative genetic map was constructed between two important genera of the
      family Pinaceae. Ten homologous linkage groups in loblolly pine (Pinus taeda L.)
      and Douglas fir (Pseudotsuga menziesii [Mirb.] Franco) were identified using
      orthologous expressed sequence tag polymorphism (ESTP) and restriction fragment
      length polymorphism (RFLP) markers. The comparative mapping revealed extensive
      synteny and colinearity between genomes of the Pinaceae, consistent with the
      hypothesis of conservative chromosomal evolution in this important plant family.
      This study reports the first comparative map in forest trees at the family
      taxonomic level and establishes a framework for comparative genomics in Pinaceae.

PMID- 15454557
TI  - Population genetics of polymorphism and divergence for diploid selection models
      with arbitrary dominance.
AB  - We develop a Poisson random-field model of polymorphism and divergence that
      allows arbitrary dominance relations in a diploid context. This model provides a
      maximum-likelihood framework for estimating both selection and dominance
      parameters of new mutations using information on the frequency spectrum of
      sequence polymorphisms. This is the first DNA sequence-based estimator of the
      dominance parameter. Our model also leads to a likelihood-ratio test for
      distinguishing nongenic from genic selection; simulations indicate that this test
      is quite powerful when a large number of segregating sites are available. We also
      use simulations to explore the bias in selection parameter estimates caused by
      unacknowledged dominance relations. When inference is based on the frequency
      spectrum of polymorphisms, genic selection estimates of the selection parameter
      can be very strongly biased even for minor deviations from the genic selection
      model. Surprisingly, however, when inference is based on polymorphism and
      divergence (McDonald-Kreitman) data, genic selection estimates of the selection
      parameter are nearly unbiased, even for completely dominant or recessive
      mutations. Further, we find that weak overdominant selection can increase, rather
      than decrease, the substitution rate relative to levels of polymorphism. This
      nonintuitive result has major implications for the interpretation of several
      popular tests of neutrality.

PMID- 15454558
TI  - Multivariate character process models for the analysis of two or more correlated
      function-valued traits.
AB  - Various methods, including random regression, structured antedependence models,
      and character process models, have been proposed for the genetic analysis of
      longitudinal data and other function-valued traits. For univariate problems, the
      character process models have been shown to perform well in comparison to
      alternative methods. The aim of this article is to present an extension of these
      models to the simultaneous analysis of two or more correlated function-valued
      traits. Analytical forms for stationary and nonstationary cross-covariance
      functions are studied. Comparisons with the other approaches are presented in a
      simulation study and in an example of a bivariate analysis of genetic covariance
      in age-specific fecundity and mortality in Drosophila. As in the univariate case,
      bivariate character process models with an exponential correlation were found to
      be quite close to first-order structured antedependence models. The simulation
      study showed that the choice of the most appropriate methodology is highly
      dependent on the covariance structure of the data. The bivariate character
      process approach proved to be able to deal with quite complex nonstationary and
      nonsymmetric cross-correlation structures and was found to be the most
      appropriate for the real data example of the fruit fly Drosophila melanogaster.

PMID- 15454559
TI  - Estimating the degree of saturation in mutant screens.
AB  - Large-scale screens for loss-of-function mutants have played a significant role
      in recent advances in developmental biology and other fields. In such mutant
      screens, it is desirable to estimate the degree of "saturation" of the screen
      (i.e., what fraction of the possible target genes has been identified). We
      applied Bayesian and maximum-likelihood methods for estimating the number of loci
      remaining undetected in large-scale screens and produced credibility intervals to
      assess the uncertainty of these estimates. Since different loci may mutate to
      alleles with detectable phenotypes at different rates, we also incorporated
      variation in the degree of mutability among genes, using either gamma-distributed
      mutation rates or multiple discrete mutation rate classes. We examined eight
      published data sets from large-scale mutant screens and found that credibility
      intervals are much broader than implied by previous assumptions about the degree
      of saturation of screens. The likelihood methods presented here are a
      significantly better fit to data from published experiments than estimates based
      on the Poisson distribution, which implicitly assumes a single mutation rate for
      all loci. The results are reasonably robust to different models of variation in
      the mutability of genes. We tested our methods against mutant allele data from a
      region of the Drosophila melanogaster genome for which there is an independent
      genomics-based estimate of the number of undetected loci and found that the
      number of such loci falls within the predicted credibility interval for our
      models. The methods we have developed may also be useful for estimating the
      degree of saturation in other types of genetic screens in addition to classical
      screens for simple loss-of-function mutants, including genetic modifier screens
      and screens for protein-protein interactions using the yeast two-hybrid method.

PMID- 15454560
TI  - Sequencing complex diseases With HapMap.
AB  - Determining the patterns of DNA sequence variation in the human genome is a
      useful first step toward identifying the genetic basis of a common disease. A
      haplotype map (HapMap), aimed at describing these variation patterns across the
      entire genome, has been recently developed by the International HapMap
      Consortium. In this article, we present a novel statistical model for directly
      characterizing specific sequence variants that are responsible for disease risk
      based on the haplotype structure provided by HapMap. Our model is developed in
      the maximum-likelihood context, implemented with the EM algorithm. We perform
      simulation studies to investigate the statistical properties of this disease
      sequencing model. A worked example from a human obesity study with 155 patients
      was used to validate this model. In this example, we found that patients carrying
      a haplotype constituted by allele Gly16 at codon 16 and allele Gln27 at codon 27
      genotyped within the beta2AR candidate gene display significantly lower body mass
      index than patients carrying the other haplotypes. The implications and
      extensions of our model are discussed.

PMID- 15454561
TI  - Toward a theory of marker-assisted gene pyramiding.
AB  - We investigate the best way to combine into a single genotype a series of target
      genes identified in different parents (gene pyramiding). Assuming that
      individuals can be selected and mated according to their genotype, the best
      method corresponds to an optimal succession of crosses over several generations
      (pedigree). For each pedigree, we compute the probability of success from the
      known recombination fractions between the target loci, as well as the number of
      individuals (population sizes) that should be genotyped over successive
      generations until the desired genotype is obtained. We provide an algorithm that
      generates and compares pedigrees on the basis of the population sizes they
      require and on their total duration (in number of generations) and finds the best
      gene-pyramiding scheme. Examples are given for eight target genes and are
      compared to a reference genotype selection method with random mating. The best
      gene-pyramiding method combines the eight targets in three generations less than
      the reference method while requiring fewer genotypings.

PMID- 15454562
TI  - Simultaneous estimation of haplotype frequencies and quantitative trait
      parameters: applications to the test of association between phenotype and
      diplotype configuration.
AB  - The analysis of the haplotype-phenotype relationship has become more and more
      important. We have developed an algorithm, using individual genotypes at linked
      loci as well as their quantitative phenotypes, to estimate the parameters of the
      distribution of the phenotypes for subjects with and without a particular
      haplotype by an expectation-maximization (EM) algorithm. We assumed that the
      phenotype for a diplotype configuration follows a normal distribution. The
      algorithm simultaneously calculates the maximum likelihood (L0max) under the null
      hypothesis (i.e., nonassociation between the haplotype and phenotype), and the
      maximum likelihood (Lmax) under the alternative hypothesis (i.e., association
      between the haplotype and phenotype). Then we tested the association between the
      haplotype and the phenotype using a test statistic, -2 log(L0max/Lmax). The above
      algorithm along with some extensions for different modes of inheritance was
      implemented as a computer program, QTLHAPLO. Simulation studies using single
      nucleotide polymorphism (SNP) genotypes have clarified that the estimation was
      very accurate when the linkage disequilibrium between linked loci was rather
      high. Empirical power using the simulated data was high enough. We applied
      QTLHAPLO for the analysis of the real data of the genotypes at the calpain 10
      gene obtained from diabetic and control subjects in various laboratories.

PMID- 15454563
TI  - Stress and survival of aging Escherichia coli rpoS colonies.
AB  - In Escherichia coli, the expression of the RpoS regulon is known to be crucial
      for survival in liquid cultures during stationary phase. By measuring cell
      viability and by transcriptome analysis, here we show that rpoS cells as well as
      wild-type cells survive when they form colonies on solid media.

PMID- 15454564
TI  - Importance of the Sir3 N terminus and its acetylation for yeast transcriptional
      silencing.
AB  - The N-terminal alanine residues of the silencing protein Sir3 and of Orc1 are
      acetylated by the NatA Nalpha-acetyltransferase. Mutations demonstrate that the N
      terminus of Sir3 is important for its function. Sir3 and, perhaps, also Orc1 are
      the NatA substrates whose lack of acetylation in ard1 and nat1 mutants explains
      the silencing defect of those mutants.

PMID- 15454565
TI  - A novel yeast mutation, rad52-L89F, causes a specific defect in Rad51-independent
      recombination that correlates with a reduced ability of Rad52-L89F to interact
      with Rad59.
AB  - We isolated a novel rad52 mutation, rad52-L89F, which specifically impairs
      recombination in rad51Delta cells. rad52-L89F displays phenotypes similar to
      rad59Delta and encodes a mutant protein impaired in its ability to interact with
      Rad59. These results support the idea that Rad59 acts in homologous recombination
      via physical interaction with Rad52.

PMID- 15454566
TI  - Functional analysis of Drosophila melanogaster gene regulatory sequences by
      transgene coplacement.
AB  - The function of putative regulatory sequences identified by comparative genomics
      can be elucidated only through experimentation. Here the effectiveness of using
      heterologous gene constructs and transgene coplacement to characterize regulatory
      sequence function is demonstrated. This method shows that a sequence in the Adh
      3'-untranslated region negatively regulates expression, independent of gene or
      chromosomal context.

PMID- 15454567
TI  - On the distribution of temporal variations in allele frequency: consequences for
      the estimation of effective population size and the detection of loci undergoing
      selection.
AB  - The effective population size (Ne) is frequently estimated using temporal changes
      in allele frequencies at neutral markers. Such temporal changes in allele
      frequencies are usually estimated from the standardized variance in allele
      frequencies (Fc). We simulate Wright-Fisher populations to generate expected
      distributions of Fc and of Fc (Fc averaged over several loci). We explore the
      adjustment of these simulated Fc distributions to a chi-square distribution and
      evaluate the resulting precision on the estimation of Ne for various scenarios.
      Next, we outline a procedure to test for the homogeneity of the individual Fc
      across loci and identify markers exhibiting extreme Fc-values compared to the
      rest of the genome. Such loci are likely to be in genomic areas undergoing
      selection, driving Fc to values greater (or smaller) than expected under drift
      alone. Our procedure assigns a P-value to each locus under the null hypothesis
      (drift is homogeneous throughout the genome) and simultaneously controls the rate
      of false positive among loci declared as departing significantly from the null.
      The procedure is illustrated using two published data sets: (i) an experimental
      wheat population subject to natural selection and (ii) a maize population
      undergoing recurrent selection.

PMID- 15454568
TI  - Gene dosage balance in cellular pathways: implications for dominance and gene
      duplicability.

PMID- 15454569
TI  - Tetraspanin CD82 controls the association of cholesterol-dependent microdomains
      with the actin cytoskeleton in T lymphocytes: relevance to co-stimulation.
AB  - T-cell activation is initiated by the concerted engagement of the T-cell receptor
      and different co-stimulatory molecules, and requires cytoskeleton-dependent
      membrane dynamics. Here, we have studied the relationships between tetraspanins,
      cytoskeleton and raft microdomains, and their relevance in T-cell signaling.
      Localization studies and density-gradient flotation experiments indicate that
      part of tetraspanins localizes in raft microdomains linked to the actin
      cytoskeleton. First, partial coalescence of lipid raft is triggered by
      tetraspanin cross-linking and results in large caps in which F-actin also
      concentrates. Second, the amount of tetraspanins, which are recovered in the
      cholesterol-dependent insoluble fractions of low and intermediate density, and
      which appears to be membrane vesicles by electron microscopy, is under
      cytoskeletal influence. Disruption of actin filaments enhances the amount of
      tetraspanins recovered in typical raft fractions, whereas F-actin-stabilizing
      agents induce the opposite effect. Our data also reveal that CD82 constitutes a
      link between raft domains and the actin cytoskeleton, which is functionally
      relevant. First, tetraspanin signaling induces a selective translocation of CD82
      from detergent-resistant membrane fractions to the cytoskeleton-associated
      pellet. Second, all functional effects linked to CD82 engagement, such as
      adhesion to culture plates, formation of actin bundles and early events of
      tyrosine phosphorylation, are abolished, or strongly reduced, by cholesterol
      depletion. We also show that dynamic relocalization of CD82 and F-actin at the
      periphery of the immune synapse is induced upon contact of T cells with antigen
      presenting cells. This suggests that the tetraspanin web might participate in the
      membrane dynamics required for proper T-cell signaling. More generally, the
      interaction of tetraspanins with raft domains and with the actin cytoskeleton
      might relate with their role in many cellular functions as membrane organizers.

PMID- 15454570
TI  - p73 competes with co-activators and recruits histone deacetylase to NF-Y in the
      repression of PDGF beta-receptor.
AB  - We investigated mechanisms of the p73alpha-mediated repression of the platelet
      derived growth factor beta-receptor (PDGFRB) promoter caused by its interaction
      with NF-Y. Treatment of cells with the histone deacetylase (HDAC) inhibitor,
      Trichostatin A, increases PDGFRB promoter activity through the CCAAT motif and
      counteracts the repression caused by p73alpha. Activation of the PDGFRB promoter
      by the co-activator p300 also occurs through the CCAAT motif. Expression of
      p73alpha counteracts both p300- and P/CAF-mediated activation of the PDGFRB
      promoter, and expression of p300 or P/CAF attenuates the p73alpha-mediated
      repression of the promoter activity. In concordance, p73alpha decreases the p300
      mediated acetylation of NF-YC, p300 competes with p73alpha for binding NF-YB, and
      P/CAF competes with p73alpha for binding NF-YB and NF-YC. Furthermore, p73alpha,
      but not the oncogenic DeltaNp73alpha, binds directly to HDAC1. We performed
      chromatin immunoprecipitation with antibodies against p73, DeltaNp73, NFYB, p300
      and HDAC1 at different periods after serum stimulation in serum-starved NIH3T3
      cells. A marked decrease of DeltaNp73, NF-YB and p300 was detected 6 hours after
      serum stimulation when the expression of PDGFRB decreased. Conversely, HDAC1 was
      found bound at its maximum and the anti-p73 detecting both TAp73 and DeltaNp73
      was found at all time points, indicating that p73, but not DeltaNp73, remains
      bound at this time. Double immunofluorescence staining of TAp73 and HDAC1
      revealed that both of these molecules exist in the nucleus at this time point,
      supporting the presence of endogenous interaction. These results suggest that p73
      and DeltaNp73 behave as physiological regulators for the transcription of the
      PDGFRB promoter.

PMID- 15454571
TI  - Maternal UNC-45 is involved in cytokinesis and colocalizes with non-muscle myosin
      in the early Caenorhabditis elegans embryo.
AB  - The Caenorhabditis elegans UNC-45 protein contains tetratricopeptide repeats and
      a domain with similarity to fungal proteins, and it differentially colocalizes
      with myosin heavy chain B in the body wall muscles of adult worms. Although it is
      essential for normal myosin filament assembly in body wall muscle development,
      strong mutants show a previously unexplained maternal effect. We show here that
      the UNC-45 protein is maternally contributed and is present in all cells of the
      early embryo whereas zygotic UNC-45 expression is only detected in the developing
      muscle cells. Embryos produced from adults with reduced germline expression of
      UNC-45 exhibit cytokinesis defects suggesting that UNC-45 has a novel role in the
      early embryo in addition to muscle development. Yeast two-hybrid screens show
      that UNC-45 can directly interact with NMY-2, a non-muscle type II myosin, and
      UNC-45 and NMY-2 colocalize at cell boundaries in early embryos. Localization of
      UNC-45 at these boundaries is dependent upon the presence of NMY-2. Our results
      suggest that UNC-45 interacts with more than one type of myosin and functions in
      the embryo to regulate cytoplasmic myosin assembly and/or stability during
      cytokinesis.

PMID- 15454572
TI  - Disruption of the cingulin gene does not prevent tight junction formation but
      alters gene expression.
AB  - Cingulin, a component of vertebrate tight junctions, contains a head domain that
      controls its junctional recruitment and protein interactions. To determine
      whether lack of junctional cingulin affects tight-junction organization and
      function, we examined the phenotype of embryoid bodies derived from embryonic
      stem cells carrying one or two alleles of cingulin with a targeted deletion of
      the exon coding for most of the predicted head domain. In homozygous (-/-)
      embryoid bodies, no full-length cingulin was detected by immunoblotting and no
      junctional labeling was detected by immunofluorescence. In hetero- and homozygous
      (+/- and -/-) embryoid bodies, immunoblotting revealed a Triton-soluble,
      truncated form of cingulin, increased levels of the tight junction proteins ZO-2,
      occludin, claudin-6 and Lfc, and decreased levels of ZO-1. The +/- and -/-
      embryoid bodies contained epithelial cells with normal tight junctions, as
      determined by freeze-fracture and transmission electron microscopy, and a biotin
      permeability assay. The localization of ZO-1, occludin and claudin-6 appeared
      normal in mutant epithelial cells, indicating that cingulin is not required for
      their junctional recruitment. Real-time quantitative reverse-transcription PCR
      (real-time qRT-PCR) showed that differentiation of embryonic stem cells into
      embryoid bodies was associated with up-regulation of mRNAs for several tight
      junction proteins. Microarray analysis and real-time qRT-PCR showed that cingulin
      mutation caused a further increase in the transcript levels of occludin, claudin
      2, claudin-6 and claudin-7, which were probably due to an increase in expression
      of GATA-6, GATA-4 and HNF-4alpha, transcription factors implicated in endodermal
      differentiation. Thus, lack of junctional cingulin does not prevent tight
      junction formation, but gene expression and tight junction protein levels are
      altered by the cingulin mutation.

PMID- 15454573
TI  - Tetraspanin protein (TSP-15) is required for epidermal integrity in
      Caenorhabditis elegans.
AB  - Epidermal integrity is essential for animal development and survival. Here, we
      demonstrate that TSP-15, a member of the tetraspanin protein family, is required
      for epithelial membrane integrity in Caenorhabditis elegans. Reduction of tsp-15
      function by mutation or by RNA interference elicits abnormalities of the
      hypodermis, including dissociation of the cuticle and degeneration of the
      hypodermis. Lethality during molting often results. Examination of GFP transgenic
      animals, genetic mosaic analysis and rescue assays revealed that TSP-15 functions
      in hyp7, a large syncytium that composes most of the hypodermis. Assays with a
      membrane-impermeable dye or leakage analysis of a hypodermal-specific marker
      indicate that the barrier function of the hypodermal membrane is impaired owing
      to the loss or reduction of TSP-15. These results indicate that TSP-15 functions
      in the maintenance of epithelial cell integrity.

PMID- 15454574
TI  - Subnuclear distribution of the largest subunit of the human origin recognition
      complex during the cell cycle.
AB  - In eukaryotes, initiation of DNA replication requires the activity of the origin
      recognition complex (ORC). The largest subunit of this complex, Orc1p, has a
      critical role in this activity. Here we have studied the subnuclear distribution
      of the overexpressed human Orc1p during the cell cycle. Orc1p is progressively
      degraded during S-phase according to a spatio-temporal program and it never
      colocalizes with replication factories. Orc1p is resynthesized in G1. In early
      G1, the protein is distributed throughout the cell nucleus, but successively it
      preferentially associates with heterochromatin. This association requires a
      functional ATP binding site and a protein region partially overlapping the bromo
      adjacent homology domain at the N-terminus of Orc1p. The same N-terminal region
      mediates the in vitro interaction with heterochromatin protein 1 (HP1).
      Fluorescence resonance energy transfer (FRET) experiments demonstrate the
      interaction of human Orc1p and HP1 in vivo. Our data suggest a role of HP1 in the
      recruitment but not in the stable association of Orc1p with heterochromatin.
      Indeed, the subnuclear distribution of Orc1p is not affected by treatments that
      trigger the dispersal of HP1.

PMID- 15454576
TI  - Mechanical stress induces profound remodelling of keratin filaments and cell
      junctions in epidermolysis bullosa simplex keratinocytes.
AB  - The outer epidermal layer of the skin is an epithelium with remarkable protective
      barrier functions, which is subject to pronounced physical stress in its day-to
      day function. A major candidate component for absorbing this stress is the K5/K14
      keratin intermediate filament network. To investigate the part played by keratins
      in stress resilience, keratinocyte cell lines were subjected to mechanical
      stress. Repeated stretch and relaxation cycles over increasing time produced
      reproducible changes in the configuration of the keratin network. When wild-type
      cells were compared with cells carrying a keratin mutation associated with severe
      epidermolysis bullosa simplex-type skin fragility, the mutant keratin filaments
      were unable to withstand the mechanical stress and progressively fragmented
      yielding aggregates and novel ring structures. The cell junctions into which the
      keratin filaments are normally anchored also progressively disassembled, with all
      components tested of the cytoplasmic plaques becoming relocated away from the
      membrane and onto the keratin rings, while integral membrane receptors integrins
      and cadherins remained at the plasma membrane. The results suggest that
      maintenance of desmosomes and hemidesmosomes may require some tension, normally
      mediated by keratin attachments.

PMID- 15454575
TI  - Xin repeats define a novel actin-binding motif.
AB  - Xin is a protein that is expressed during early developmental stages of cardiac
      and skeletal muscles. Immunolocalization studies indicated a peripheral
      localization in embryonic mouse heart, where Xin localizes with beta-catenin and
      N-cadherin. In adult tissues, Xin is found primarily in the intercalated discs of
      cardiomyocytes and the myotendinous junctions of skeletal muscle cells, both
      specialized attachment sites of the myofibrillar ends to the sarcolemma. A large
      part of the Xin protein consists of unique 16 amino acid repeats with unknown
      function. We have investigated the characteristics of the Xin repeats by
      transfection experiments and actin-binding assays and ascertained that, upon
      expression in cultured cells, these repeats bind to and stabilize the actin-based
      cytoskeleton. In vitro co-sedimentation assays with skeletal muscle actin
      indicated that they not only directly bind actin filaments, but also have the
      capability of arranging microfilaments into networks that sediment upon low-speed
      centrifugation. Very similar repeats were also found in 'Xin-repeat protein 2'
      (XIRP2), a novel protein that seems to be expressed mainly in striated muscles.
      Human XIRP2 contains 28 Xin repeats with properties identical to those of Xin. We
      conclude that the Xin repeats define a novel, repetitive actin-binding motif
      present in at least two different muscle proteins. These Xin-repeat proteins
      therefore constitute the first two members of a novel family of actin-binding
      proteins.

PMID- 15454577
TI  - The GIN4 family kinase, Cdr2p, acts independently of septins in fission yeast.
AB  - Two relatives of the GIN4 protein kinase family, Cdr1p and Cdr2p, exist in the
      yeast Schizosaccharomyces pombe. Although in Saccharomyces cerevisiae GIN4
      related kinases influence septin ring organization and septin rings influence the
      localization and function of GIN4-related protein kinases, it is unknown whether
      this relationship is conserved in S. pombe. Here, we have probed the relationship
      between Cdr2p activity and septins and find that Cdr2p and septins are
      functionally independent. Cdr2p localizes in a cortical band overlying the
      nucleus during interphase, whose dimension is proportional to cell length, and to
      a medial ring structure in late mitosis. Both localizations are septin
      independent and disrupted by treatment with filipin. Structure/function analysis
      indicates that the intracellular targeting domain of Cdr2p is largely contained
      within its non-catalytic C-terminus. Cdr2 protein kinase activity, while
      unimportant for its localization, is critical for its cell cycle function. Our
      data indicate that Cdr2p functions at two positions within the cell at discrete
      cell cycle stages to influence the timing of mitotic entry and cytokinesis,
      respectively.

PMID- 15454578
TI  - Increased importin-beta-dependent nuclear import of the actin modulating protein
      CapG promotes cell invasion.
AB  - CapG (gCap39) is a ubiquitous gelsolin-family actin modulating protein involved
      in cell signalling, receptor-mediated membrane ruffling, phagocytosis and
      motility. CapG is the only gelsolin-related actin binding protein that localizes
      constitutively to both nucleus and cytoplasm. Structurally related proteins like
      severin and fragmin are cytoplasmic because they contain a nuclear export
      sequence that is absent in CapG. Increased CapG expression has been reported in
      some cancers but a causal role for CapG in tumour development, including invasion
      and metastasis, has not been explored. We show that moderate expression of green
      fluorescent protein-tagged CapG (CapG-EGFP) in epithelial cells induces invasion
      into collagen type I and precultured chick heart fragments. Nuclear export
      sequence-tagged CapG-EGFP fails to induce invasion, whereas point mutations in
      the nuclear export sequence permitting nuclear re-entry restore cellular
      invasion. Nuclear import of CapG is energy-dependent and requires the cytosolic
      receptor importin beta but not importin alpha. Nuclear CapG does not possess
      intrinsic transactivation activity but suppresses VP16 transactivation of a
      luciferase reporter gene in a dose-dependent manner. Furthermore, invasion
      requires signalling through the Ras-phosphoinositide 3-kinase pathway and Cdc42
      or RhoA, but not Rac1. We show for the first time active nuclear import of an
      actin binding protein, and our findings point to a role for nuclear CapG in
      eliciting invasion, possibly through interfering with the cellular transcription
      machinery.

PMID- 15454579
TI  - Macroscopic folding and replication of the homogeneously staining region in late
      S phase leads to the appearance of replication bands in mitotic chromosomes.
AB  - The chromosomal G/R bands are alternating domains differing in their nucleotide
      sequence biases. The bands are also related to the time of replication: pulse
      labeling during S phase makes the replication sites as visible as replication
      bands that are close to the G/R bands in mitotic chromosomes. We previously
      showed that a plasmid bearing a mammalian replication origin efficiently
      generated a chromosomal homogeneously staining region (HSR). Here, we analyze the
      replication of this artificial HSR and show that it was replicated at the last
      stage of S phase. The HSR was composed of plasmid repeats only; nonetheless, we
      found that replication sites pulse-labeled during late S phase appeared as bands
      in the mitotic HSR and their number was dependent on the length of the HSR.
      Therefore, replication bands might not arise from sequence information per se. To
      understand the chronological order of appearance of replication sites, we
      performed a double pulse-chase experiment using IdU and CldU. Replication of the
      entire HSR required 100-120 minutes. During this period, the replicated sites
      appeared as bands at the first and last stages, but in between were apparently
      scattered along the entire HSR. An analysis of S-phase nuclei revealed that the
      replication started at the periphery of the globular HSR domain, followed by
      initiation in the internal domain. The replicated HSR appeared as a ring or a
      pair of extended spirals in late G2-phase nuclei. To account for these findings,
      we present a model in which the HSR is folded as a coiled-coil structure that is
      replicated from the outside to the inside in S phase nuclei.

PMID- 15454580
TI  - Microarray analyses identify molecular biomarkers of Atlantic salmon macrophage
      and hematopoietic kidney response to Piscirickettsia salmonis infection.
AB  - Piscirickettsia salmonis is the intracellular bacterium that causes salmonid
      rickettsial septicemia, an infectious disease that kills millions of farmed fish
      each year. The mechanisms used by P. salmonis to survive and replicate within
      host cells are not known. Piscirickettsiosis causes severe necrosis of
      hematopoietic kidney. Microarray-based experiments with QPCR validation were used
      to identify Atlantic salmon macrophage and hematopoietic kidney genes
      differentially transcribed in response to P. salmonis infection. Infections were
      confirmed by microscopy and RT-PCR with pathogen-specific primers. In infected
      salmon macrophages, 71 different transcripts were upregulated and 31 different
      transcripts were downregulated. In infected hematopoietic kidney, 30 different
      transcripts were upregulated and 39 different transcripts were downregulated. Ten
      antioxidant genes, including glutathione S-transferase, glutathione reductase,
      glutathione peroxidase, and cytochrome b558 alpha- and beta-subunits, were
      upregulated in infected macrophages but not in infected hematopoietic kidney.
      Changes in redox status of infected macrophages may allow these cells to tolerate
      P. salmonis infection, raising the possibility that treatment with antioxidants
      may reduce hematopoietic tissue damage caused by this rickettsial infection. The
      downregulation of transcripts involved in adaptive immune responses (e.g., T cell
      receptor alpha-chain and C-C chemokine receptor 7) in infected hematopoietic
      kidney but not in infected macrophages may contribute to infection-induced kidney
      tissue damage. Molecular biomarkers of P. salmonis infection, characterized by
      immune-relevant functional annotations and high fold differences in expression
      between infected and noninfected samples, may aid in the development of anti
      piscirickettsial vaccines and therapeutics.

PMID- 15454581
TI  - DNA microarray analysis of gene expression in alveolar epithelial cells in
      response to TNFalpha, LPS, and cyclic stretch.
AB  - Recent evidence suggests that alveolar epithelial cells (AECs) may contribute to
      the development, propagation, and resolution of acute lung injury (ALI)/acute
      respiratory distress syndrome (ARDS). Proinflammatory cytokines, pathogen
      products, and injurious mechanical ventilation are important contributors of
      excessive inflammatory responses in the lung. In the present study, we used cDNA
      microarrays to define the gene expression patterns of A549 cells (an AEC line) in
      the early stages of three models of pulmonary parenchymal cell activation: cells
      treated with tumor necrosis factor-alpha (TNFalpha) (20 ng/ml),
      lipopolysaccharide (LPS, 1 microg/ml), or cyclic stretch (20% elongation) for
      either 1 h or 4 h. Differential gene expression profiles were determined by gene
      array analysis. TNFalpha induced an inflammatory response pattern, including
      induction of genes for chemokines, inflammatory mediators, and cell surface
      membrane proteins. TNFalpha also increased genes related to pro- and anti
      apoptotic proteins, signal transduction proteins, and transcriptional factors.
      TNFalpha further induced a group of genes that may form a negative feedback loop
      to silence the NFkappaB pathway. Stimulation of AECs with mechanical stretch
      changed cell morphology and activated Src protein tyrosine kinase. The
      combination of TNFalpha plus stretch enhanced or attenuated expression of
      multiple genes. LPS decreased microfilament polymerization but had less impact on
      NFkappaB translocation and gene expression. Results from this study indicate that
      AECs can tailor their response to different stimuli or/and combination of stimuli
      and subsequently play an important role in acute inflammatory responses in the
      lung.

PMID- 15454582
TI  - Stability of sufentanil citrate with levobupivacaine HCl in NaCl 0.9% infusion
      after microwave freeze-thaw treatment.
AB  - BACKGROUND: Sufentanil is a powerful central anesthetic and analgesic of the
      opiate family that can be used with levobupivacaine for epidural administration.
      Advance preparation of intravenous solution could be useful to improve quality,
      time management, and cost-savings of drug delivery. OBJECTIVE: To investigate how
      freezing, long-term storage, and microwave thawing can affect the stability of
      sufentanil citrate and levobupivacaine HCl in NaCl 0.9% (saline) (w/v) polyvinyl
      chloride (PVC) bags. METHODS: The stability of 5 bags of solution containing
      sufentanil 500 microg and levobupivacaine 625 mg per 500 mL of saline solution in
      PVC bags was studied after freezing for 4 months at -30 degrees C, thawing in a
      microwave oven with a validated cycle, and storage at 4 degrees C. The
      concentrations of the drugs were measured by HPLC using a reversed-phase column,
      a mobile phase consisting of 18% acetonitrile (v/v) in tertabutyl ammonium
      hydrogen sulfate buffer 0.03 M pH 3.00 +/- 0.05, and UV detection at 235 nm for
      sufentanil and 260 nm for levobupivacaine. Visual inspection and pH measurement
      were also performed. RESULTS: No color change or precipitation was observed.
      Sufentanil and levobupivacaine were stable for at least 70 days at 4 degrees C
      after freezing and thawing. Throughout this period, the 95% lower confidence
      limit of the concentration-time profile remained >90% of the initial
      concentration. During this period, the pH value remained stable. CONCLUSIONS:
      Within the limits defined here, a mixture of sufentanil citrate and
      levobupivacaine HCl may be prepared in advance and kept frozen.

PMID- 15454583
TI  - A community-based educational intervention to improve antithrombotic drug use in
      atrial fibrillation.
AB  - BACKGROUND: Despite evidence that antithrombotics are effective in reducing the
      risk of stroke in atrial fibrillation (AF), they remain underused. OBJECTIVE: To
      perform a controlled trial of a comprehensive educational program promoting the
      rational prescribing of antithrombotics for stroke prevention in AF. METHODS: The
      intervention was conducted in Southern Tasmania, Australia, using Northern
      Tasmania as a control area. General practitioners were sent locally produced
      guidelines on stroke risk stratification and antithrombotic drug use in AF, which
      were followed by academic detailing visits. Outcomes were measured using
      evaluation feedback from the general practitioners, and drug utilization data
      were provided by a series of patients presenting to the hospital with an
      admission diagnosis of AF and dispensing of antithrombotic therapy under the
      Australian Pharmaceutical Benefits Scheme. RESULTS: During the educational
      intervention, 272 guidelines were mailed and, subsequently, 162 general
      practitioners were visited and the guidelines discussed. Hospital admission data
      before and after the intervention revealed a significant increase in the use of
      warfarin in patients at high risk of stroke (33% vs 46% of eligible patients; p <
      0.05). Analysis of prescription data for warfarin also indicated that the
      increase in use of warfarin within the intervention region was significantly
      greater than for the control region (p < 0.001). CONCLUSIONS: The educational
      program described here led to a significant increase in the prescribing of
      warfarin for stroke prevention in patients with AF.

PMID- 15454584
TI  - Auditory hallucinations elicited by combined meclizine and metaxalone use at
      bedtime.

PMID- 15454585
TI  - Progression of myelodysplasia during low-dose methotrexate therapy in rheumatoid
      arthritis.

PMID- 15454586
TI  - Enhancing pharmacist involvement in weight management--time to get with the
      program.

PMID- 15454587
TI  - Anecdote bad, story good.

PMID- 15454588
TI  - Interview with Dame Rosemary Rue.

PMID- 15454589
TI  - Policies for disease prevention in Germany in the European context: a comparative
      analysis.
AB  - BACKGROUND: In Europe important differences exist concerning policies for the
      prevention of common diseases. In most cases these cannot be explained by the
      underlying epidemiology. However, successful policies should have a measurable
      effect on disease epidemiology. There has been little research comparing the
      effect of national preventive policies on disease-specific mortality. OBJECTIVES:
      To describe the mortality trends for three health problems representing the three
      levels of prevention in Germany and in selected European countries, which are of
      interest for the disease under question. To relate epidemiological trends to
      preventive policies at the national level and at the level of the European Union
      (EU). METHODS: Comparison of age-standardized mortality rates for road traffic
      accidents, cervical cancer and diabetes mellitus in the period 1970-2002, using
      routine data. Analysis of disease-specific prevention policies in countries that
      deviate from the general trend in the EU, with a special focus on developments in
      Germany. RESULTS: The development of mortality rates during the last 30 years for
      road traffic accidents, cervical cancer and diabetes mellitus varied
      substantially across Europe. Although the evidence linking specific public
      policies to epidemiological trends is sparse and often limited to ecological
      studies, a number of epidemiological changes can be plausibly linked to specific
      policies in the countries concerned. CONCLUSION: Successful preventive policies
      exist for all health problems reviewed. The current status of implementation of
      these policies can only be interpreted in the historical and political context of
      the countries concerned. The role of epidemiology to guide health policy
      decisions is under-utilized, as is the regulatory framework for disease and
      injury prevention at the level of the EU. Less formal policy measures such as
      European clinical guidelines are equally scarce. More rigorous comparative health
      services research is needed to formulate evidence-based policies for disease
      prevention.

PMID- 15454590
TI  - Establishment and evaluation of a smoking cessation clinic in Hong Kong: a model
      for the future service provider.
AB  - BACKGROUND: In the West, the effectiveness of smoking cessation programmes is
      well established. Smoking cessation programmes in the East are rare. We evaluated
      a pilot smoking cessation health centre (SCHC) of the Hong Kong Council on
      Smoking and Health (COSH). METHODS: The clinic operated 3 days a week from 6 to 9
      pm. Smokers were recruited mainly by low cost publicity. Trained counsellors
      provided individual counselling and a 1 week free supply of nicotine replacement
      therapy (NRT). The programme was evaluated in terms of process, outcome and cost.
      RESULTS: During August 2000 to January 2002, 2212 calls were received through the
      clinic hotline and 1203 smokers attended the clinic. Eight hundred and forty-one
      were successfully followed up at 12 months. Based on intention-to-treat analysis,
      the 7 day point prevalence quit rate at 12 months (not smoking any cigarette
      during the past 7 days at the 12 month follow-up) was 27 per cent (95 per cent
      confidence interval, CI 25-30 per cent). The average cost per quitter was USD 339
      (USD 440 including NRT cost for a 1 week free supply). Other benefits included
      training of healthcare workers and medical students, organization of seminars,
      health talks and self-help groups, and promotion of research and training.
      CONCLUSION: This first evaluation of a clinic-based smoking cessation service in
      Asia showed that the service was acceptable to Chinese smokers. The quit rate in
      this pilot part-time clinic is comparable to those of full-time and better funded
      clinics in the West. A part-time smoking cessation clinic is a promising model
      for piloting smoking cessation services in the East.

PMID- 15454591
TI  - Prevalence and awareness of risk factors and behaviours of coronary heart disease
      in an urban population of Karachi, the largest city of Pakistan: a community
      survey.
AB  - OBJECTIVES: To estimate the prevalence and awareness of risk factors and risk
      behaviours of coronary heart disease (CHD) in the lower middle class residing in
      urban localities of Karachi, a mega city of Pakistan. METHODS: The design
      consisted of a cross-sectional community based survey in the lower middle class
      urban localities of Karimabad, Garden and Kharardar in Karachi, Pakistan. One
      thousand four hundred adults (18 years and above) registered with the Aga Khan
      Development Network (AKDN) participated in the survey. Life style, self-reported
      risk variables, blood pressure and anthropometric measurements were recorded.
      RESULTS: Prevalence of hypertension, high cholesterol and diabetes were 38.5,
      10.7 and 9.1 per cent, respectively. 52.2 per cent of the sample was overweight
      or obese; 64.8 per cent never exercised; 11.9 per cent had two or more major risk
      factors of CHD. CONCLUSION: The communities studied showed a very high prevalence
      of hypertension, obesity and a sedentary life style. Despite a high literacy
      rate, awareness regarding CHD risk factors was low. This underlines the need for
      measures to increase awareness regarding CHD and its risk factors and a healthy
      lifestyle in the developing countries.

PMID- 15454592
TI  - How physically active are South Asians in the United Kingdom? A literature
      review.
AB  - BACKGROUND: Moderate physical activity is protective against coronary heart
      disease (CHD) and diabetes, both important public health problems among UK South
      Asian (Indian, Pakistani and Bangladeshi) ethnic groups. We assessed the evidence
      that physical activity is lower in South Asian groups than in the general
      population. METHODS: We carried out a systematic literature review of studies
      describing levels of physical activity and fitness in UK South Asians using
      MEDLINE, EMBASE, the Cochrane databases, hand searching of relevant journals and
      review of reference lists. RESULTS: We identified 12 studies in adults and five
      in children. Various methods were used to assess physical activity and fitness,
      but all the studies reported lower levels among South Asian groups. The
      differences were substantial, particularly among women and older people. For
      example, the Health Survey for England found that Indian, Pakistani and
      Bangladeshi men were 14, 30 and 45 per cent less likely than the general
      population to meet current guidelines for physical activity. Limited information
      was provided about translation and adaptation of questionnaires. CONCLUSION:
      Levels of physical activity were lower in all South Asian groups than the general
      population and patterns of activity differed. No studies used validated measures.
      Insufficient attention has been paid to issues of cross-cultural equivalence.
      With these caveats, low levels of physical activity among UK South Asian ethnic
      groups may contribute to their increased risk of diabetes and CHD. Closer
      attention to validity, translation and adaptation is necessary to monitor changes
      and assess the effectiveness of interventions to increase physical activity.

PMID- 15454593
TI  - Gender differences in management after acute myocardial infarction: not 'sexism'
      but a reflection of age at presentation.
AB  - OBJECTIVE: To test whether women receive less intensive treatment and fewer risk
      stratification tests following acute myocardial infarction (MI), than men.
      METHODS: A retrospective study of medical records in all district general
      hospitals and tertiary referral centres for cardiology in Wales was performed.
      Patients (n = 1595, of which 989 were men) admitted to hospital over 4 months
      with a diagnosis of acute MI had their case notes reviewed for treatment,
      stratification of risk factors and secondary prevention. Data were analysed for
      differences in treatment between men and women and whether these could be
      attributed to age at presentation. RESULTS: Women were older than men at
      presentation [mean age 75 (SD 11) versus 66 (12) years, p < 0.01]; fewer women
      received thrombolysis (34 versus 44 per cent) and low molecular weight heparin
      (63 versus 71 per cent) (both p < 0.001); and women had higher 30 day mortality
      (28 versus 17 per cent, p < 0.001). Fewer women received cardiac catheterization,
      investigations to identify high risk, drugs for secondary prevention on discharge
      and referral to cardiac rehabilitation. However, intensities of treatment,
      investigation and secondary prevention were strongly related to age and, after
      adjusting for age, gender differences remained only for thrombolysis and exercise
      testing. CONCLUSION: Although women receive fewer investigations and treatments
      than men, this potential gender bias can be explained by age. The lower use of
      treatment and investigation among older patients draws attention to the lack of
      direct evidence of effectiveness for these patients. Further studies are needed
      to confirm effectiveness of investigations and treatments in older patients.

PMID- 15454594
TI  - Impact of the introduction of fee for service payments on types of minor surgical
      procedures undertaken by general practitioners: observational study.
AB  - The 1990 general practitioners (GPs) contract introduced item of service payment
      for minor surgery, payable for six categories of procedure. Early review showed
      no substitution of cheaper procedures for more expensive treatments. Detailed
      payment data from six Health Authorities for the period 1993-2000 show an 11 per
      cent increase in claims, largely accounted for by the rise in cautery,
      incorporating cryotherapy. Cryotherapy is no more effective at treating warts
      than cheap commercially available products, but is quite profitable for GPs. This
      is yet another example of item of service payment distorting treatment
      priorities. The new GP contract, and the initiative to develop GPs with special
      interests in dermatology and minor surgery, will allow primary care trusts to
      develop minor surgery undertaken by appropriately skilled and experienced GPs,
      and which reflects the needs of the population.

PMID- 15454595
TI  - Why has antibiotic prescribing for respiratory illness declined in primary care?
      A longitudinal study using the General Practice Research Database.
AB  - BACKGROUND: Antibiotic prescribing by general practitioners (GPs) increased in
      the 1980s and peaked in 1995. Prescribing volumes subsequently fell by over a
      quarter between 1995 and 2000, mostly accounted for by reduced antibiotic
      prescribing for acute respiratory illnesses. We aimed to investigate changes in
      consultation rates and the proportion of consultations with antibiotics
      prescribed for different types of respiratory tract infections. METHODS: Data
      were derived from 108 UK general practices, covering a mean of 642,685 patients,
      reporting data to the General Practice Research Database (GPRD) continuously
      between 1994 and 2000. OUTCOME MEASURES: annual age- and sex-standardized
      consultation rates for 11 different acute respiratory infections per 1000
      registered patients and proportions of these consultations resulting in an
      antibiotic prescription. RESULTS: The standardized consultation rate for 'any
      respiratory infection' declined by 35 per cent from 422 to 273 per 1000
      registered patients, per year. The largest relative reductions in consultation
      rates were observed for 'common cold' (50 per cent), 'laryngitis' (43 per cent)
      and 'sore throat' (43 per cent). The standardized proportion of consultations
      that resulted in an antibiotic prescription for 'any respiratory infection'
      declined from 79 per cent in 1994 to 67 per cent in 2000. The largest relative
      reductions in antibiotic prescribing rates occurred in patients recorded as
      suffering from 'influenza' (52 per cent), 'upper respiratory tract infections'
      (33 per cent) and 'laryngitis' (30 per cent). Overall, antibiotic prescriptions
      for all acute respiratory infections declined by 45 per cent. CONCLUSION: The
      reduction in antibiotic prescribing in common respiratory infections between 1994
      and 2000 has occurred partly because GPs are prescribing antibiotics less
      frequently when patients consult but mainly because there are fewer consultations
      with these conditions. Further work should aim to understand the reasons for the
      decline in consultations for respiratory infections and whether further
      reductions in antibiotic prescribing are feasible.

PMID- 15454596
TI  - Continuity within primary palliative care: an audit of general practice out-of
      hours co-operatives.
AB  - BACKGROUND: The transfer of information between general practitioners (GPs) and
      their out-of-hours providers on vulnerable patient groups is essential to ensure
      continuity of care. This will be critical when, in 2006, NHS Direct will triage
      and route all out-of-hours calls. This study investigates the current use of
      information handover systems for palliative care patients within four out-of
      hours co-operatives. METHODS: Paper records of all 13,460 contacts during August
      2002 were scrutinized. Using a standardized data extraction form we recorded
      details on all palliative or terminal contacts, and the existence of information
      handover. RESULTS: Across the four co-operatives, 2.1 per cent of all calls were
      from palliative care patients; co-operatives held handover information for
      between one (1.2 per cent) and 13 (32.5 per cent) of these patients. CONCLUSION:
      The systems in place to alert these co-operatives to the needs of palliative care
      patients are currently under-utilized. As services move towards an integrated
      approach, scrutiny of information transfer systems and encouragement of GPs and
      district nurses to update information, may help to ensure better continuity of
      care

PMID- 15454597
TI  - Opportunities for prevention of 'clinically significant' knee pain: results from
      a population-based cross sectional survey.
AB  - BACKGROUND: There is little UK-based evidence on the prevalence and predictors of
      knee pain associated with disability across all adult ages. We aimed to estimate
      the prevalence of 'clinically significant' knee pain, identify and assess the
      population impact of independent risk factors, and estimate levels of healthcare
      need. METHODS: A cross-sectional survey of three general practice populations was
      conducted. Adults (n = 5752) were mailed a screening questionnaire (phase I).
      Those reporting predominant or isolated knee pain were sent a detailed
      questionnaire (phase II), with a further sub-sample invited for clinical
      examination (phase III). Logistic regression was used to identify independent
      risk factors and population attributable fractions were calculated. RESULTS: The
      1 month period prevalence of 'all reported' knee pain was 19 per cent, of which
      about a third was disabling and a fifth intense and disabling. Obesity,
      deprivation and South Asian ethnicity were each associated with a 3-4-fold
      increased risk of knee pain with disability (after age/sex adjustment). The
      attributable fraction estimate for raised body mass index (BMI) was 36 per cent
      (27-44 per cent) - the population impact of being overweight was greater than
      that of being obese. Thirteen per cent of all adults reported a previous primary
      care consultation, 7 per cent reported previous secondary care referral for knee
      pain, and 4.5 per cent (2.7-6.2 per cent) of the adult population were currently
      receiving or in need of specialist treatment. CONCLUSION: The high population
      impact of being overweight (BMI 25-29) or obese (BMI 30 or more) has implications
      for primary prevention. The estimates of previous healthcare usage, and of levels
      of met and unmet need, are useful for healthcare planning.

PMID- 15454598
TI  - Antenatal screening for HIV; are those who refuse testing at higher risk than
      those who accept testing?
AB  - BACKGROUND: The UK Department of Health recommends that all pregnant women are
      offered screening for infection with human immunodeficiency virus (HIV) and had
      encouraged maternity units to achieve uptake targets of 90 per cent by the end of
      2002. Many maternity units fail to meet this target and there is concern that
      those women who are still refusing testing may include a higher proportion of
      women at high risk of infection. In consequence, those infected with HIV are not
      being identified and are not receiving the antiviral treatment, which would be of
      benefit to them and reduce the risk of transmission of HIV to their babies.
      METHODS: A retrospective audit of HIV screening uptake in women who were found to
      be infected with hepatitis B virus (HBV) and in those who were not infected with
      HBV was carried out in order to explore further the characteristics of
      'acceptors' and 'refusers' of HIV screening. RESULTS: The overall uptake rate of
      HIV screening in the West Midlands population served by the National Blood
      Service was 60 per cent in 2001 and 74 per cent in 2002. The prevalence of HBV
      infection was found to be twice as high (0.39 per cent) in those who had refused
      an HIV test compared with those who had accepted a test (0.21 per cent) (p =
      0.022). CONCLUSION: There is good evidence that women refusing HIV antenatal
      screening have a higher prevalence of another blood-borne virus, indicating
      clearly that further effort must be made to increase the screening uptake and
      fully integrate HIV screening with other antenatal tests.

PMID- 15454599
TI  - What are the most appropriate methods of surveillance for monitoring an emerging
      respiratory infection such as SARS?
AB  - Effective surveillance is necessary for the successful management of emerging
      infection. It allows public health protection measures such as contact tracing
      and isolation to be put in place. This study aimed to find the most appropriate
      surveillance method for a disease like SARS. Existing surveillance methods were
      evaluated against a set of new criteria in a qualitative manner. Influenza and
      tuberculosis (TB) surveillance were used as models. A literature search was
      undertaken to find relevant evidence. The results show that TB surveillance is
      more appropriate than influenza surveillance as a model because it is more
      complete in its reporting. Clinician-based reporting is better than laboratory
      based because it is more timely. The results suggest a clinician-based
      notification system would be the most appropriate form of surveillance for a
      disease like SARS for public health purposes.

PMID- 15454600
TI  - Uptake for cervical screening by ethnicity and place-of-birth: a population-based
      cross-sectional study.
AB  - Previous research indicates low screening uptake among South Asian women. We
      aimed to generate contemporary evidence of uptake by ethnicity using the
      screening records of eligible women resident in Manchester (n = 72613). Uptake
      among South Asians was lower than among other women, a difference explained by
      area- and practice-level confounding. A higher proportion of South Asians were
      recorded as 'never screened', an effect only partially explained by confounding.
      In practices with relatively large South Asian populations, uptake was higher
      among South Asians. Women born in a diverse range of overseas countries had
      uptake rates below 60 per cent and approximately a third of women born overseas
      were recorded as 'never screened'. If comprehensive coverage is to be achieved in
      inner city areas attention should now focus on the needs of a diverse range of
      ethnic minority groups other than South Asians. The routine collection of
      ethnicity data in primary care is also indicated.

PMID- 15454601
TI  - From efficacy to effectiveness: case studies in unemployment research.
AB  - There have been few attempts to implement and disseminate programmes to address
      the psychological health impact of unemployment despite the burden of this
      problem upon public health and health services. One approach that has
      demonstrated efficacy in promoting both psychological health and employment for
      this group is based upon the principles of cognitive behavioural therapy (CBT).
      We have been involved in three interventions based upon CBT to improve the
      psychological health of people who are unemployed, delivered through existing
      service structures in Australia: employment support agencies, general practice
      and mental health services. In this paper, we examine our experiences in
      conducting research within these service organizations using a framework for
      collaboration between researchers and services based upon intersectoral action.
      While effective collaboration can facilitate the implementation of research
      within systems, poor collaboration can impact upon the integrity of research
      designs. In our experience, it was the capacity of service organizations to
      address the psychological health impact of unemployment in particular that had a
      significant effect upon adoption of the intervention. Service organizations did
      not have structures to support the rigorous evaluation of interventions nor did
      they have funding arrangements that facilitated effective collaboration on
      research to address psychological issues. The dissemination of evidence-based
      interventions like CBT to populations of people who are unemployed in Australia
      is hindered by the absence of an accessible and appropriate system through which
      to address the psychological health impact of unemployment.

PMID- 15454602
TI  - The challenges of systematically reviewing public health interventions.

PMID- 15454603
TI  - Communicable Disease and Health Protection Quarterly Review: January to March
      2004. From the Health Protection Agency, Communicable Disease Surveillance
      Centre.

PMID- 15454604
TI  - Reducing inequalities in non-fatal accidents in England.

PMID- 15454605
TI  - Risk of congenital anomalies near the Byker waste combustion plant.

PMID- 15454607
TI  - Situational awareness in public health.

PMID- 15454608
TI  - Significant social class gradient in breast cancer types and the outcome of
      potentially unnecessary mastectomies.

PMID- 15454609
TI  - HBV vaccination should be performed in service centres for drug users: an Italian
      experience.

PMID- 15454610
TI  - Reverse transcriptase at bacterial telomeres.

PMID- 15454611
TI  - Biography of Erin K. O'Shea.

PMID- 15454612
TI  - Biography of Vernon M. Ingram.

PMID- 15454613
TI  - Imaging of rheumatoid arthritis: can MR imaging be used to monitor cellular
      response of disease?

PMID- 15454614
TI  - Quality and safety revolution in health care.

PMID- 15454615
TI  - Learning theory in radiology education.

PMID- 15454616
TI  - Supplemental oxygen causes increased signal intensity in subarachnoid
      cerebrospinal fluid on brain FLAIR MR images obtained in children during general
      anesthesia.
AB  - PURPOSE: To prospectively test the hypothesis that high levels of the fraction of
      inspired oxygen (Fio(2)) during general anesthesia cause subarachnoid
      cerebrospinal fluid (CSF) hyperintensity during fluid-attenuated inversion
      recovery (FLAIR) magnetic resonance (MR) imaging. MATERIALS AND METHODS: At brain
      MR imaging during general anesthesia with propofol, two FLAIR sequences were
      performed in 20 children with American Society of Anesthesiologists physical
      status classification system grades of 3 or lower. The first FLAIR sequence was
      performed with the child breathing 100% oxygen; the second was performed with the
      child breathing 30% oxygen. CSF signal intensity was quantified on a three-point
      ordinal scale (0 = hypointense to brain parenchyma, 1 = isointense to brain
      parenchyma, 2 = hyperintense to brain parenchyma) by a pediatric neuroradiologist
      who was blinded to the Fio(2) level. The Wilcoxon signed rank test was used to
      determine if CSF hyperintensity was correlated with Fio(2). RESULTS: CSF
      hyperintensity was present in all 20 children (age range, 1.9-16.7 years; 12
      children were boys) when the Fio(2) was 100%. The hyperintensity partially or
      completely disappeared in the basilar cisterns (P <.001) and cerebral sulcal
      subarachnoid space (P <.001) after Fio(2) was reduced from 100% to 30%.
      CONCLUSION: These findings are consistent with the hypothesis that increased
      arterial oxygen tension and consequently increased CSF Po(2) resulting from
      administration of high Fio(2) during general anesthesia are responsible for the
      increased CSF signal intensity noted on brain FLAIR MR images.

PMID- 15454617
TI  - The dural tail sign.

PMID- 15454619
TI  - Case 75: erythropoietic hemochromatosis.

PMID- 15454620
TI  - Measurement of serum calcium concentration after administration of
      gadoversetamide in dogs.
AB  - PURPOSE: To measure serum calcium concentration with three different analytic
      methods after administration of gadoversetamide and three other gadolinium
      chelates in dogs. MATERIALS AND METHODS: Six dogs were injected with 0.1-, 0.3-,
      1.0-, and 3.0-mmol/kg doses of gadoversetamide; 1.0-mmol/kg doses of gadodiamide,
      gadopentetate, and gadoteridol; and a 6-mL/kg dose of saline. Baseline blood
      samples were collected before injection; 5, 15, 30, and 60 minutes after each
      treatment; and 2, 4, 6, 12, and 24 hours after each treatment. Serum calcium
      levels were measured with inductively coupled plasma mass spectrometry, an
      arzenazo III dye assay, and an orthocresolphalthalin (OCP) complexone system.
      Analysis of variance coupled with the Dunnett procedure was used to compare serum
      calcium concentrations at different time points after injection with baseline
      values. RESULTS: Administration of gadoversetamide caused no decrease in serum
      calcium levels, as measured with inductively coupled plasma mass spectrometry or
      arzenazo III analytic techniques. In contrast, OCP assays showed a significant (P
      <.05) decrease in serum calcium values after administration of gadoversetamide.
      The decrease in serum calcium values peaked immediately after injection, and
      serum calcium values quickly returned to baseline. Injection of gadodiamide
      caused a significant (P <.05) decrease in the value of serum calcium when
      analyzed with the OCP technique but not when analyzed with inductively coupled
      plasma mass spectrometry or arzenazo III assays. In contrast, administration of
      gadopentetate or gadoteridol produced no significant change in serum calcium
      values, regardless of analytic method. CONCLUSION: Gadoversetamide and
      gadodiamide caused a transient artifact in measurement of serum calcium levels
      with an OCP assay but not with an arzenazo III technique or inductively coupled
      plasma mass spectrometry. The presence of gadopentetate or gadoteridol in the
      blood did not affect measurement of serum calcium levels.

PMID- 15454621
TI  - Abdominal aortic aneurysm: contrast-enhanced US for missed endoleaks after
      endoluminal repair.
AB  - PURPOSE: To evaluate contrast material-enhanced ultrasonography (US) for
      depiction of endoleaks after endovascular abdominal aortic aneurysm repair (or
      endovascular aneurysm repair [EVAR]) in patients with aneurysm enlargement and no
      evidence of endoleak. MATERIALS AND METHODS: From November 1998 to February 2003,
      112 patients underwent EVAR. At follow-up, duplex US and biphasic multi-detector
      row computed tomographic (CT) angiography were performed. In 10 patients (group
      A), evident aneurysm enlargement was observed, with no evidence of complications,
      at both CT angiography and duplex US. Group A patients, 10 men (mean age, 69.6
      years +/- 10 [standard deviation]), underwent US after intravenous bolus
      injection of a second-generation contrast agent, with continuous low-mechanical
      index (0.01-0.04) real-time tissue harmonic imaging. Group B patients, 10 men
      (mean age, 71.3 years +/- 8.2) with aneurysm shrinkage and no evidence of
      complications, and group C patients, 10 men (mean age, 73.2 years +/- 6) with CT
      angiographic evidence of endoleak, underwent contrast-enhanced US. Digital
      subtraction angiography (DSA) was performed in groups A and C. Endoleak detection
      and characterization were assessed with imaging modalities used in groups A-C; at
      contrast-enhanced US, time of detection of endoleak, persistence of sac
      enhancement, and morphology of enhancement were evaluated. RESULTS: In group A,
      contrast-enhanced US depicted one type I, six type II, one type III, and two
      undefined endoleaks that were not detected at CT angiography. All leakages were
      characterized by slow and delayed echo enhancement detected at longer than 150
      seconds after contrast agent administration. DSA results confirmed findings in
      all patients; percutaneous treatment was performed. In group B, contrast-enhanced
      US did not show echo enhancement; in group C, results with this modality
      confirmed findings at CT angiography and DSA. CONCLUSION: Contrast-enhanced US
      depicts endoleaks after EVAR, particularly when depiction fails with other
      imaging modalities.

PMID- 15454622
TI  - Sixteen-detector row CT of abdomen and pelvis: study for optimization of Z-axis
      modulation technique performed in 153 patients.
AB  - PURPOSE: To retrospectively determine the optimal noise indexes required to
      obtain diagnostically acceptable computed tomographic (CT) images of the abdomen
      and pelvis with z-axis modulation. MATERIALS AND METHODS: Ninety-five patients
      underwent 16-section multi-detector row CT of the abdomen and pelvis with z-axis
      modulation at noise indexes of 10.5, 11.0, 11.5, and 12.0 HU with 10-380 mA.
      Subsequently, 58 patients were scanned at noise indexes of 12.5 and 15.0 HU with
      75-380 mA. The weights of all subjects were recorded, and transverse and
      anteroposterior diameters were measured. The CT images were evaluated for
      abnormalities and graded for image quality in terms of noise and diagnostic
      acceptability by using a five-point scale. Objective noise in the liver
      parenchyma was measured, and the tube current was recorded at each section in all
      153 patients. Statistical analyses were performed to determine the appropriate
      noise index and to assess the effect of patient weight and abdominal diameters on
      image noise and diagnostic acceptability at different noise indexes. Tube current
      time products (in milliampere seconds) at various noise indexes were compared
      with those at CT previously performed without z-axis modulation. RESULTS: No
      significant difference in subjective image noise or diagnostic acceptability was
      found at noise indexes of 10.5-15.0 HU (P =.14), and objective noise was
      significantly inferior only at a noise index of 15.0 HU (P =.009). Compared with
      CT scanning at a 10.5-HU noise index, CT scanning at 12.5- and 15.0-HU noise
      indexes yielded, respectively, 10.0% and 41.3% reductions in radiation exposure.
      Patient weight and abdominal diameters affected subjective image quality.
      CONCLUSION: Use of a 15.0-HU noise index at 75-380 mA results in acceptable
      subjective image noise and diagnostic acceptability but significantly greater
      objective image noise at routine abdominal-pelvic CT. For greater image quality
      demands, a noise index of 12.5 HU results in acceptable image quality and a 19.6%
      reduction in radiation exposure.

PMID- 15454623
TI  - CT colonography with computer-aided detection: automated recognition of ileocecal
      valve to reduce number of false-positive detections.
AB  - The ileocecal valve (ICV) is a common cause of false-positive detections of
      polyps at computed tomographic (CT) colonography with computer-aided detection
      (CAD). The authors developed a CAD algorithm for differentiating the ICV from a
      true polyp and evaluated this algorithm by using two colonoscopy-confirmed CT
      colonography data sets. Data sets 1 and 2 consisted of the data obtained at CT
      colonographic examinations performed in 20 and 40 patients, respectively. Forty
      of these patients had at least one polyp 1 cm or larger. For data set 1, the
      proposed ICV recognition algorithm eliminated three of nine (33%; 95% confidence
      interval [CI]: 8%, 70%) false-positive CAD detections that were attributable to
      the ICV and none of the true-positive polyp detections. For data set 2, with use
      of identical parameters, the algorithm eliminated 11 of 18 (61%; 95% CI: 36%,
      83%) false-positive detections that were attributable to the ICV and none of the
      true-positive detections. The thresholds used to recognize the ICV were a mean
      internal CT attenuation of less than -124 HU and a volume of greater than 1.5
      cm(3). The proposed algorithm successfully recognized the ICV and eliminated it
      in some cases. This result is clinically important because, by reducing the
      frequency of a common cause of false-positive detections, this algorithm may
      improve the efficiency of physicians who use CAD.

PMID- 15454624
TI  - Pancreatic transplants: noninvasive evaluation with secretin-augmented mr
      pancreatography and MR perfusion measurements--preliminary results.
AB  - Feasibility of secretin-augmented magnetic resonance (MR) pancreatography and
      dynamic contrast material-enhanced MR measurements for evaluation of functional
      status of pancreatic allografts was determined by quantifying the excretion and
      perfusion of the grafts. Ten patients were included prospectively before
      pancreatic transplantation. Dynamic T2-weighted sequences after secretin
      stimulation and dynamic contrast-enhanced T1-weighted gradient-echo sequences
      were performed. Area under the curve and maximum signal intensity-to-time ratio
      were determined in selected regions of interest. Biochemical parameters, Doppler
      ultrasonography, and/or surgery were standards for final diagnosis. Patients with
      normal outcome (n = 7) produced 236 mL +/- 104 (standard deviation) of pancreatic
      juice, and patients with dysfunctional grafts (n = 3) produced 42 mL +/- 25. Area
      under the curve and maximum signal intensity-to-time ratio provided thresholds of
      0.5 and 0.3, respectively, for distinction between functional and dysfunctional
      grafts. Secretin-augmented MR pancreatography combined with MR perfusion
      measurements may aid in differentiation between patients with and those without
      graft dysfunction.

PMID- 15454625
TI  - Automatic dose reduction should not mask needs for individual dose reduction.

PMID- 15454626
TI  - Importance of using controls in in vivo experiments.

PMID- 15454627
TI  - Hepatitis D-related cirrhosis and risk of hepatocellular carcinoma development.

PMID- 15454628
TI  - Transgluteal approach for percutaneous drainage of deep pelvic abscesses: how to
      avoid injury to vital structures.

PMID- 15454629
TI  - Cell signaling and the genesis of neuropathic pain.
AB  - Damage to the nervous system can cause neuropathic pain, which is in general
      poorly treated and involves mechanisms that are incompletely known. Currently
      available animal models for neuropathic pain mainly involve partial injury of
      peripheral nerves. Multiple inflammatory mediators released from damaged tissue
      not only acutely excite primary sensory neurons in the peripheral nervous system,
      producing ectopic discharge, but also lead to a sustained increase in their
      excitability. Hyperexcitability also develops in the central nervous system (for
      instance, in dorsal horn neurons), and both peripheral and spinal elements
      contribute to neuropathic pain, so that spontaneous pain may occur or normally
      innocuous stimuli may produce pain. Inflammatory mediators and aberrant neuronal
      activity activate several signaling pathways [including protein kinases A and C,
      calcium/calmodulin-dependent protein kinase, and mitogen-activated protein
      kinases (MAPKs)] in primary sensory and dorsal horn neurons that mediate the
      induction and maintenance of neuropathic pain through both posttranslational and
      transcriptional mechanisms. In particular, peripheral nerve lesions result in
      activation of MAPKs (p38, extracellular signal-regulated kinase, and c-Jun N
      terminal kinase) in microglia or astrocytes in the spinal cord, or both, leading
      to the production of inflammatory mediators that sensitize dorsal horn neurons.
      Activity of dorsal horn neurons, in turn, enhances activation of spinal glia.
      This neuron-glia interaction involves positive feedback mechanisms and is likely
      to enhance and prolong neuropathic pain even in the absence of ongoing peripheral
      external stimulation or injury. The goal of this review is to present evidence
      for signaling cascades in these cell types that not only will deepen our
      understanding of the genesis of neuropathic pain but also may help to identify
      new targets for pharmacological intervention.

PMID- 15454630
TI  - Working status among Dutch patients with rheumatoid arthritis: work disability
      and working conditions.
AB  - OBJECTIVES: To assess work disability and variables associated with work
      disability among Dutch patients with rheumatoid arthritis (RA). METHODS: A
      questionnaire on working status was filled out by 296 patients of working age.
      Employment and work disability rates adjusted for age and sex from the Dutch
      population were determined using indirect standardization. Cox proportional
      hazard analysis was used to assess baseline predictors of work disability in a
      subgroup of patients (n = 195). RESULTS: After a mean disease duration of 4.3 yr,
      patients had a 0.78 (95% CI 0.67-0.88) chance of being employed and a 2.14 (95%
      CI 1.75-2.54) risk of being work disabled when compared with the Dutch
      population. Functional disability and job type at the start of the disease were
      predictors of future work disability. In total, 48 (37%) currently employed
      patients had changed their working conditions, of which reduced working hours
      (46%), reduced pacing of work (42%) and help from colleagues (49%) were the most
      important alterations. Of the 60 work disabled patients without a paid job, only
      11 patients (18%) would be willing to work again. CONCLUSION: This study shows
      that the adjusted employment rates were lower and that work disability rates were
      higher in patients with RA when compared with the general Dutch population. In
      addition, a substantial number of employed patients had to change their working
      conditions due to RA. Only a minority of work disabled RA patients was willing to
      return to the paid labour force.

PMID- 15454631
TI  - Adenosine and methotrexate polyglutamate concentrations in patients with juvenile
      arthritis.
AB  - OBJECTIVE: In contrast to the anti-proliferative properties of high-dose
      methotrexate (MTX) its anti-inflammatory mechanism of action in rheumatic
      diseases has been attributed to increased adenosine accumulation, most likely
      caused by long-lived intracellular MTX polyglutamates. The aim of this study was
      to assess adenosine concentrations in MTX-treated and untreated children and to
      relate it to MTX polyglutamate concentration measured in erythrocytes and to the
      therapeutic efficacy. METHODS: Adenosine and MTX-polyglutamate concentrations in
      erythrocytes (EMTX) were assessed in venous blood samples taken before the next
      MTX dose in 30 patients treated long-term for juvenile idiopathic arthritis (JIA)
      and in 16 untreated matched controls. The blood concentration of adenosine was
      measured by the liquid chromatography/tandem mass spectrometry (LC-MS/MS) method
      and EMTX by an enzymatic assay. Therapeutic efficacy was assessed using the
      preliminary definition of improvement in JIA patients. RESULTS: Mean blood
      adenosine concentration in MTX-treated patients was 48.05 nmol/l (s.d. 10.1) vs
      49.6 nmol/l (s.d. 12.5) in untreated controls (P=0.55). Mean EMTX was 215.56
      nmol/l (s.d. 212.9). No significant correlation was found between adenosine
      concentrations and MTX dose or EMTX (P=0.8 and 0.6, respectively). Adenosine
      concentration did not differ in clinical responders when compared with non
      responders (P=0.9). CONCLUSIONS: We have shown that there is no impact of
      effective MTX dose represented by EMTX on blood adenosine concentration in JIA
      patients. If MTX anti-inflammatory action is mediated by adenosine it is likely
      that local release of adenosine at inflamed tissues is responsible for its action
      which may not be reflected by sustained increase of its blood concentration.

PMID- 15454632
TI  - The oocyte and its role in regulating ovulation rate: a new paradigm in
      reproductive biology.
AB  - Ovulation rate in mammals is determined by a complex exchange of hormonal signals
      between the pituitary gland and the ovary and by a localised exchange of hormones
      within ovarian follicles between the oocyte and its adjacent somatic cells. From
      examination of inherited patterns of ovulation rate in sheep, point mutations
      have been identified in two oocyte-expressed genes, BMP15 (GDF9B) and GDF9.
      Animals heterozygous for any of these mutations have higher ovulation rates (that
      is, + 0.8-3) than wild-type contemporaries, whereas those homozygous for each of
      these mutations are sterile with ovarian follicular development disrupted during
      the preantral growth stages. Both GDF9 and BMP15 proteins are present in
      follicular fluid, indicating that they are secreted products. In vitro studies
      show that granulosa and/or cumulus cells are an important target for both growth
      factors. Multiple immunisations of sheep with BMP15 or GDF9 peptide protein
      conjugates show that both growth factors are essential for normal follicular
      growth and the maturation of preovulatory follicles. Short-term (that is, primary
      and booster) immunisation with a GDF9 or BMP15 peptide-protein conjugate has been
      shown to enhance ovulation rate and lamb production. In summary, recent studies
      of genetic mutations in sheep highlight the importance of oocyte-secreted factors
      in regulating ovulation rate, and these discoveries may help to explain why some
      mammals have a predisposition to produce two or more offspring rather than one.

PMID- 15454633
TI  - Fyn kinase-tubulin interaction during meiosis of rat eggs.
AB  - Prior to fertilization, the spindle of vertebrate eggs must remain stable and
      well organized during the second meiotic meta-phase arrest (MII). In a previous
      study we have determined that the completion of meiosis is a Src family kinase
      (SFK)-dependent event. In the current study we have used the SFK inhibitors,
      SU6656 and PP2, and demonstrated that inhibition of SFKs caused the formation of
      a disorganized spindle. The observation that proper organization of an MII
      spindle is an SFK-dependent process, combined with our previous finding that Fyn
      kinase is localized at the microtubules (MTs), prompted us to examine the
      potential role of Fyn in MT signaling. Our results show an association between
      Fyn and tubulin, the ability of Fyn to phosphorylate tubulin in vitro and
      stimulation of meiosis completion by injection of a constitutively active form of
      Fyn (CAF). We suggested that SFKs mediate significant functions during the
      organization of the MII spindle. In view of CAF injection experiments, and of the
      pronounced concentration of Fyn kinase at the spindle, we propose that Fyn may
      play an important role in some aspects of the spindle functions, possibly those
      involving the MTs.

PMID- 15454634
TI  - Development of mouse-specific contraceptive vaccines: infertility in mice
      immunized with peptide and polyepitope antigens.
AB  - Mouse-specific immunocontraceptive peptides have been identified in mouse
      proteins with key roles in reproduction from sequence comparisons to other
      species and tested for efficacy as immunocontraceptive antigens. Peptides were
      derived from granulocyte-macrophage colony-stimulating factor (GMCSF), the
      placental 27 kDa heat-shock protein (HSP), leukemia inhibitory factor receptor
      (LIFR), oviduct glycoprotein (OGP), proliferin (PLF), prolactin (PRL), sperm
      protein SP56 and mouse zona pellucida subunits 1 and 3 (ZP1, ZP3). Fertility of
      female BALB/c mice was reduced after immunization with several peptides either
      conjugated to a carrier protein or in the form of recombinant polyepitopes. The
      most effective conjugated peptides (SP56, GMCSF and PRL) induced peptide-specific
      serum antibodies and reduced fertility by 50%. Fertility of mice was also reduced
      after immunization with polyepitope antigens containing up to five different
      peptides fused to maltose-binding protein, but antibodies were not produced
      against all the encoded peptides. The most effective polyepitope antigen
      (containing PLF, SP56, ZP1 and ZP3 peptides) reduced fertility by 50% but induced
      only SP56 and ZP1 antibodies. We demonstrate that lack of antibody response to a
      given peptide epitope (ZP3) can be overcome if repeated copies are used in the
      polyepitope antigen construct, but the effect varies between mouse strains. We
      conclude that infertility induced in mice with a range of peptide-based vaccines
      is dependent on antigen formulation and genetic factors but does not necessarily
      correlate with peptide-specific antibody levels. In light of these results,
      strategies to improve the efficacy of peptide-based antifertility vaccines are
      discussed.

PMID- 15454635
TI  - The role of calcium/calmodulin-dependent protein kinase II on the inactivation of
      MAP kinase and p34cdc2 kinase during fertilization and activation in pig oocytes.
AB  - The objective of this study was to investigate the role of calmodulin-dependent
      protein kinase II (CaMKII) during fertilization in the pig. Since it has been
      reported that CaMKII is involved in the capacitation and acrosome reaction of
      spermatozoa, we tested whether supplementation with the CaMKII inhibitor, KN-93,
      in the fertilization medium affected sperm penetration. The results showed that
      the addition of KN-93 in the fertilization medium significantly reduced the rate
      of sperm penetration into oocytes. However, pre-treatment with KN-93 before in
      vitro fertilization (i.v.f.) did not significantly affect sperm penetration, but
      it did affect pronuclear formation in a dose-dependent manner. In the oocytes pre
      treated with KN-93 before i.v.f. and then co-cultured with spermatozoa without
      the drug, the decrease in p34cdc2 kinase and the cyclin B1 level were
      significantly suppressed as compared with those in penetrated oocytes without
      treatment with KN-93. However, the decrease in MAP kinase activity was not
      affected by KN-93. Additional treatment with KN-93 after Ca2+ ionophore treatment
      also inhibited the reduction in p34cdc2 kinase activity and the cyclin B1 level,
      but not MAP kinase activity. Treatment with KN-92, an inactive KN-93 analogue,
      did not significantly affect sperm penetration and pronuclear formation. In
      conclusion, the activation of CaMKII by artificial stimuli or sperm stimulated
      the disruption of cyclin B1 and the inactivation of p34cdc2 kinase, but did not
      affect MAP kinase inactivation during oocyte activation in pigs.

PMID- 15454636
TI  - Interrelationships among follicles during the common-growth phase of a follicular
      wave and capacity of individual follicles for dominance in mares.
AB  - The changing diameter interrelationships among follicles during the interval from
      emergence to deviation (common-growth phase) were studied in 59 mares. All
      follicles of > or =6.0 mm were ablated 10 days after ovulation. The four largest
      follicles of the postablation wave were ranked D1, D2, D3 and D4 at the expected
      beginning of deviation (D1 > or = 20.0 mm), according to descending diameter. The
      four follicles were also ranked independently, according to order of emergence at
      6.0-6.9 mm as E1 (first to emerge), E2, E3 and E4. The follicles emerged during
      1.3 +/- 0.1 to 3.1 +/- 0.1 days, and expected deviation began 6.5 +/- 0.1 days
      after ablation. The frequency of emerging follicles becoming the largest follicle
      at the beginning of deviation was different (P < 0.0001; chi-square test) among
      follicles E1 (61%), E2 (25%), E3 (9%) and E4 (5%). There were no differences in
      growth rates among the four follicles throughout the common-growth phase
      (overall, 2.8 +/- 0.04 mm/day). The differences in diameters between follicles E1
      and E2 were similar between 3 days (2.7 +/- 0.2 mm) and 6 days (2.9 +/- 0.4 mm)
      after ablation. In controls and after ablation of D1; D1 and D2; or D1, D2 and D3
      at the expected beginning of deviation, the largest remaining follicle became
      dominant in 26 of 34 mares (76%). In 10 of 15 mares (67%), the second-largest
      follicle became dominant when the largest follicle was ablated 1 or 2 days after
      the expected beginning of deviation. Results indicated the following: 1) the
      first follicle to emerge maintained its diameter advantage in most mares and
      average diameter growth rates were similar among the four follicles throughout
      the common-growth phase; 2) the hypothesis was supported that the capacity for
      dominance is similar among the four largest follicles at the beginning of
      deviation, but dominance by a smaller follicle is blocked when a larger follicle
      is present; and 3) the second-largest follicle retained the capacity for
      dominance in most mares for as long as 2 days after the beginning of deviation.

PMID- 15454637
TI  - The human corpus luteum: which cells have progesterone receptors?
AB  - Studies comparing the regressing corpus luteum with the rescued corpus luteum
      have demonstrated that human chorionic gonadotrophin (hCG) has effects on cell
      types that do not express hCG receptors. As progesterone synthesis is hCG
      dependent and the corpus luteum has been shown to express genomic progesterone
      receptors, progesterone is a candidate molecule for these paracrine effects. This
      study aimed to define the cellular localisation of progesterone receptors in the
      human corpus luteum using dual-staining immunohistochemistry for genomic
      progesterone receptors and specific cellular markers. Well-characterised corpora
      lutea (n = 12) from different stages of the luteal phase were studied. The same
      distribution was observed in all corpora lutea examined. The steroidogenic cells
      (3beta-hydroxysteroid dehydrogenase positive) and both theca-lutein (17alpha
      hydroxylase positive) and granulosa-lutein (aromatase positive) express
      progesterone receptors, as do stromal fibroblasts (vimentin positive, fibroblast
      antigen positive). Vascular endothelial cells (CD31 positive), pericytes (alpha
      smooth muscle actin positive), macrophages (CD68 positive) and fibroblasts within
      the central clot do not express nuclear progesterone receptors. Progesterone is a
      candidate messenger molecule for the effects of hCG on the matrix
      metalloproteinase-producing stromal fibroblasts. Some of the effects of hCG on
      steroidogenic cells may be mediated by progesterone, but its effects on blood
      vessels and macrophages require alternate paracrine signalling mechanisms. In
      addition, there appears to be at least two fibroblast populations in the corpus
      luteum.

PMID- 15454638
TI  - Endometrial expression of calbindin (CaBP)-d28k but not CaBP-d9k in primates
      implies evolutionary changes and functional redundancy of calbindins at
      implantation.
AB  - The endometrium is hostile to embryo implantation except during the 'window of
      receptivity'. A change in endometrial gene expression is required for the
      development of receptivity. Calbindin-d9k (CaBP-d9k) and calbindin-d28k (CaBP
      d28k) are proteins possessing EF-hand motifs which have high affinity for Ca2+
      ions. Previously, it has been demonstrated that, in mouse endometrium, the
      expression of both calbindins is highly regulated during implantation and that
      both proteins play critical but functionally redundant roles at implantation.
      This study was the first to determine the expression of these two calbindins in
      the human and rhesus monkey endometrium. Initial RT-PCR analysis demonstrated
      that CaBP-d28k but not CaBP-d9k mRNA expression is detectable in the endometrium
      of both species. Western blot analysis confirmed the presence of immuno-reactive
      CaBP-d28k protein in the primate endometrium. Furthermore, the endometrial
      expression pattern of CaBP-d28k mRNA and protein was examined by Northern blot
      analysis and immunohistochemistry respectively in both species across the
      menstrual cycle and during early pregnancy. Semi-quantitative statistical
      analysis of the immunohistochemistry results revealed that, in the human, CaBP
      d28k protein expression was maximal in luminal and glandular epithelium during
      the mid-secretory phase, coinciding with the time when the endometrium is
      receptive to embryo implantation. Expression in rhesus monkey showed a similar
      trend. These results suggest that, in the primate endometrium, only CaBP-d28k is
      expressed and that the specific regulation of this calbindin is potentially
      important for the establishment of uterine receptivity.

PMID- 15454639
TI  - Number of conceptuses in utero affects porcine fetal muscle development.
AB  - Unmodified, third parity, control sows (CTR; n = 30) or sows subjected to
      unilateral oviduct ligation before breeding (LIG; n = 30), were slaughtered at
      either day 30 or day 90 of gestation and used to determine the effects of numbers
      of conceptuses in utero on prenatal, and particularly muscle fibre, development.
      Ovulation rate, number of conceptuses in utero, placental and fetal size, and
      (day 90 sows) fetal organ and semitendinosus muscle development were recorded.
      Tubal ligation reduced (P < 0.05) the number of viable embryos at day 30 and
      fetuses at day 90. Placental weight at day 30 and day 90, and fetal weight at day
      90, were lower (P < 0.05) in CTR sows. All body organs except the brain were
      lighter, and the brain:liver weight ratio was higher in CTR fetuses (P < 0.05),
      indicative of brain sparing and intrauterine growth restriction in fetuses from
      CTR sows. Muscle weight, muscle cross-sectional area and the total number of
      secondary fibres were also lower (P < 0.05) in CTR fetuses. The number of primary
      fibres, the secondary:primary muscle fibre ratio, and the distribution of myosin
      heavy chain-Ibeta, -IIa, fetal and embryonic isoforms did not differ between
      groups. Thus, even the relatively modest uterine crowding occurring naturally in
      CTR sows negatively affected placental and fetal development and the number of
      secondary muscle fibres. Consequences of more extreme crowding in utero on fetal
      and postnatal development, resulting from changing patterns of early embryonic
      survival, merit further investigation.

PMID- 15454640
TI  - Embryonic exposure to oestrogen causes eggshell thinning and altered shell gland
      carbonic anhydrase expression in the domestic hen.
AB  - Eggshell thinning among wild birds has been an environmental concern for almost
      half a century. Although the mechanisms for contaminant-induced eggshell thinning
      are not fully understood, it is generally conceived to originate from exposure of
      the laying adult female. Here we show that eggshell thinning in the domestic hen
      is induced by embryonic exposure to the synthetic oestrogen ethynyloestradiol.
      Previously we reported that exposure of quail embryos to ethynyloestradiol caused
      histological changes and disrupted localization of carbonic anhydrase in the
      shell gland in the adult birds, implying a functional disturbance in the shell
      gland. The objective of this study was to examine whether in ovo exposure to
      ethynyloestradiol can affect eggshell formation and quality in the domestic hen.
      When examined at 32 weeks of age, hens exposed to ethynyloestradiol in ovo (20
      ng/g egg) produced eggs with thinner eggshells and reduced strength (measured as
      resistance to deformation) compared with the controls. These changes remained 14
      weeks later, confirming a persistent lesion. Ethynyloestradiol also caused a
      decrease in the number of shell gland capillaries and in the frequency of shell
      gland capillaries with carbonic anhydrase activity. These data suggested that a
      disrupted carbonic anhydrase expression was involved in the mechanism for the
      oestrogen-induced eggshell thinning found in this study. The results support our
      hypothesis that eggshell thinning in avian wildlife can result from a structural
      and functional malformation in the shell gland, induced by xeno-oestrogen
      exposure during embryonic development.

PMID- 15454641
TI  - Characterization of endothelin-1 and nitric oxide generating systems in corpus
      luteum-derived endothelial cells.
AB  - Endothelium-derived endothelin-1 (ET-1) and nitric oxide (NO) are pivotal
      regulators of corpus luteum (CL) function. To have a better insight into their
      synthesis and action, members of the ET system (ET-1, ET converting enzyme (ECE
      1) isoforms a-d, ETA and ETB receptors) along with NO synthase (NOS) isoforms-
      endothelial (e)NOS and inducible (i)NOS--were quantified in CL-derived
      endothelial cells (CLEC). The expression of these genes in microvascular CLEC,
      obtained by lectin-coated magnetic beads, was compared with cells removed from
      the luteal microenvironment and maintained in culture for different durations,
      and with endothelial cells (EC) derived from a large blood vessel (i.e. bovine
      aortic endothelial cells, BAEC). The profile of gene expression in the different
      EC types was determined by quantitative real-time PCR. Freshly isolated EC from
      mid-cycle CL exhibited high ET-1 receptor expression (both ETA and ETB), low ET-1
      synthesizing ability (both prepro (pp) ET-1 and ECE-1), but elevated iNOS - the
      high throughput NOS isoform. The distinct phenotype of CLEC was lost soon after
      an overnight culture. ETA and ETB receptor levels declined, ppET-1 levels
      increased while iNOS was reduced. These changes were extenuated during long-term
      culture of CLEC. The general pattern of gene expression in BAEC and long-term
      cultured CLEC was similar yet some differences, reminiscent of freshly isolated
      CLEC, remained: ECE-1c, ETB receptor and NOS isoforms were expressed differently
      in BAEC as compared with lines of CLEC. This study suggests that the luteal
      microenvironment is necessary to sustain the selective phenotype of its resident
      endothelial cells. The inverse relationship between ppET-1 and iNOS observed in
      freshly isolated CLEC and in cultured cells is physiologically significant and
      suggests that ET-1 and NO may modulate the production of each other.

PMID- 15454642
TI  - Effects of re-immunization of heifers against inhibin on hormonal profiles and
      ovulation rate.
AB  - To study the effect of re-immunization against inhibin on ovarian response and
      hormonal profiles, Japanese beef heifers (n = 5) were re-immunized three times
      with inhibin vaccine (recombinant ovine inhibin alpha-subunit in oil emulsion,
      125 microg ml(-1)) one year after the primary immunization. Control heifers (n =
      5) were injected with placebo (Montanide: Marcol adjuvant alone). Oestrous cycles
      were synchronized by using prostaglandin F2alpha (PGF2alpha) and ovarian response
      was monitored daily by ultrasonography. Blood samples were collected by jugular
      venipuncture for assessment of hormonal levels and inhibin antibody titres. In
      contrast to controls, inhibin re-immunized heifers generated antibodies against
      inhibin rapidly reaching a peak level 9 days after the first booster injection.
      The mean concentrations of FSH in re-immunized cows increased significantly in
      comparison with controls. In addition, there was a significant increase in
      oestradiol-17beta and progesterone levels in re-immunized cows compared with
      controls. Inhibin re-immunized heifers had a significant increase in small (> or
      =4 < 7 mm), medium (> or =7 < 10 mm) and large (> or =10 mm in diameter) sized
      follicles. Moreover, the mean ovulation rate was 5.0 +/- 1.1 after the third
      booster injection in re-immunized heifers compared with control heifers (single
      ovulation). These results clearly demonstrate that re-immunization of inhibin can
      be used to enhance ovarian follicular development and ovulation rate.
      Furthermore, the great number of follicles is a potential source of oocytes that
      could be harvested for in vitro fertilization and embryo transfer programmes.

PMID- 15454643
TI  - Chemotherapy for advanced lung cancer: is the glass half full or half empty?

PMID- 15454644
TI  - The HRCT scan pursuing real life pathology.

PMID- 15454645
TI  - Pi MZ and COPD: will we ever know?

PMID- 15454646
TI  - Environmental allergen exposure, sensitisation and asthma: from whole populations
      to individuals at risk.

PMID- 15454647
TI  - Chemotherapy versus supportive care in advanced non-small cell lung cancer:
      improved survival without detriment to quality of life.
AB  - BACKGROUND: In 1995 a meta-analysis of randomised trials investigating the value
      of adding chemotherapy to primary treatment for non-small cell lung cancer
      (NSCLC) suggested a small survival benefit for cisplatin-based chemotherapy in
      each of the primary treatment settings. However, the meta-analysis included many
      small trials and trials with differing eligibility criteria and chemotherapy
      regimens. METHODS: The aim of the Big Lung Trial was to confirm the survival
      benefits seen in the meta-analysis and to assess quality of life and cost in the
      supportive care setting. A total of 725 patients were randomised to receive
      supportive care alone (n = 361) or supportive care plus cisplatin-based
      chemotherapy (n = 364). RESULTS: 65% of patients allocated chemotherapy (C)
      received all three cycles of treatment and a further 27% received one or two
      cycles. 74% of patients allocated no chemotherapy (NoC) received thoracic
      radiotherapy compared with 47% of the C group. Patients allocated C had a
      significantly better survival than those allocated NoC: HR 0.77 (95% CI 0.66 to
      0.89, p = 0.0006), median survival 8.0 months for the C group v 5.7 months for
      the NoC group, a difference of 9 weeks. There were 19 (5%) treatment related
      deaths in the C group. There was no evidence that any subgroup benefited more or
      less from chemotherapy. No significant differences were observed between the two
      groups in terms of the pre-defined primary and secondary quality of life end
      points, although large negative effects of chemotherapy were ruled out. The
      regimens used proved to be cost effective, the extra cost of chemotherapy being
      offset by longer survival. CONCLUSIONS: The survival benefit seen in this trial
      was entirely consistent with the NSCLC meta-analysis and subsequent similarly
      designed large trials. The information on quality of life and cost should enable
      patients and their clinicians to make more informed treatment choices.

PMID- 15454648
TI  - Relationship between peripheral airway dysfunction, airway obstruction, and
      neutrophilic inflammation in COPD.
AB  - BACKGROUND: Considerable research has been conducted into the nature of airway
      inflammation in chronic obstructive pulmonary disease (COPD) but the relationship
      between proximal airways inflammation and both dynamic collapse of the peripheral
      airways and HRCT determined emphysema severity remains unknown. A number of
      research tools have been combined to study smokers with a range of COPD
      severities classified according to the GOLD criteria. METHODS: Sixty five
      subjects (11 healthy smokers, 44 smokers with stage 0-IV COPD, and 10 healthy non
      smokers) were assessed using lung function testing and HRCT scanning to quantify
      emphysema and peripheral airway dysfunction and sputum induction to measure
      airway inflammation. RESULTS: Expiratory HRCT measurements and the
      expiratory/inspiratory mean lung density ratio (both indicators of peripheral
      airway dysfunction) correlated more closely in smokers with the severity of
      airflow obstruction (r = -0.64, p<0.001) than did inspiratory HRCT measurements
      (which reflect emphysema severity; r = -0.45, p<0.01). Raised sputum neutrophil
      counts also correlated strongly in smokers with HRCT indicators of peripheral
      airway dysfunction (r = 0.55, p<0.001) but did not correlate with HRCT indicators
      of the severity of emphysema. CONCLUSIONS: This study suggests that peripheral
      airway dysfunction, assessed by expiratory HRCT measurements, is a determinant of
      COPD severity. Airway neutrophilia, a central feature of COPD, is closely
      associated with the severity of peripheral airway dysfunction in COPD but is not
      related to the overall severity of emphysema as measured by HRCT.

PMID- 15454649
TI  - Chronic obstructive pulmonary disease in alpha1-antitrypsin PI MZ heterozygotes:
      a meta-analysis.
AB  - BACKGROUND: Severe alpha(1)-antitrypsin deficiency, usually related to
      homozygosity for the protease inhibitor (PI) Z allele, is a proven genetic risk
      factor for chronic obstructive pulmonary disease (COPD). The risk of COPD in PI
      MZ heterozygous individuals is controversial. METHODS: A search of MEDLINE from
      January 1966 to May 2003 identified studies that examined the risk of COPD in PI
      MZ individuals and studies that measured forced expiratory volume in 1 second
      (FEV(1)) in heterozygotes. RESULTS: In 16 studies that reported COPD as a
      categorical outcome, the combined odds ratio (OR) for PI MZ versus PI MM (normal
      genotype) was 2.31 (95% CI 1.60 to 3.35). The summary OR was higher in case
      control studies (OR 2.97; 95% CI 2.08 to 4.26) than in cross sectional studies
      (OR 1.50; 95% CI 0.97 to 2.31) and was attenuated in studies that adjusted for
      cigarette smoking (OR 1.61; 95% CI 0.92 to 2.81). In seven studies that reported
      FEV(1) as a continuous outcome there was no difference in mean FEV(1) between PI
      MM and PI MZ individuals. CONCLUSIONS: Case-control studies showed increased odds
      of COPD in PI MZ individuals, but this finding was not confirmed in cross
      sectional studies. Variability in study design and quality limits the
      interpretation. These results are consistent with a small increase in risk of
      COPD in all PI MZ individuals or a larger risk in a subset. Future studies that
      adjust for smoking and include other COPD related phenotypes are required to
      conclusively determine the risk of COPD in PI MZ heterozygotes.

PMID- 15454650
TI  - Decreased expression of interleukin 13 in human lung emphysema.
AB  - BACKGROUND: The overexpression of interferon (IFN)gamma or interleukin (IL)-13 in
      the adult murine lung induces the development of changes that mirror human lung
      emphysema. METHODS: IL-13 and IFNgamma expression was determined in lung samples
      from five groups of PATIENTS: severe emphysema without alpha(1)-antitrypsin
      deficiency (SE+, n = 10); severe emphysema with alpha(1)-antitrypsin deficiency
      (SE-, n = 5); mild localised emphysema (ME, n = 8); non-emphysema smokers (NE-S,
      n = 9), and non-emphysema non-smokers (NE-NS, n = 11). Lung IL-13 and IFNgamma
      mRNA were analysed by RT-PCR. Lung concentrations of IL-13 protein were assessed
      by ELISA. RESULTS: The expression of IFNgamma mRNA was similar in patients with
      or without emphysema. IL-13 mRNA was markedly decreased in the SE+ group compared
      with the SE- (p = 0.04), ME (p = 0.02), and non-emphysema groups (p = 0.01). IL
      13 mRNA correlated with forced expiratory volume in 1 second (r = 0.5, p = 0.04)
      and arterial oxygen tension (r = 0.45, p = 0.03) in emphysema patients. In
      contrast to the non-emphysematous lung, IL-13 protein was below the detection
      limit of the assay in most emphysematous lung homogenates. CONCLUSION: The lung
      IL-13 content is reduced in patients with severe emphysema without alpha(1)
      antitrypsin deficiency.

PMID- 15454651
TI  - Early allergen exposure, skin prick responses, and atopic wheeze at age 5 in
      English children: a cohort study.
AB  - BACKGROUND: For many years it has been assumed that the risk of childhood
      respiratory allergies is related to allergen exposures in early life. There are,
      however, few prospective data in support. We aimed to examine this relationship
      in a representative cohort of children born in Ashford, Kent (UK). METHODS: 625
      children (94% of those eligible) were followed from birth to the age of 5.5 years
      at which time 552 underwent skin prick testing to extracts of house dust mite and
      cat fur allergens. Maternal reports of wheeze in the last year were collected by
      interview. These outcomes were related to individual domestic concentrations of
      Der p 1 and Fel d I allergens estimated from dust collection at the age of 8
      weeks. RESULTS: 10% of children were sensitised to house dust mite or cat at age
      5.5 years; 7% had atopic wheeze. No significant relationships between allergen
      exposure and either sensitisation or wheeze were found but, on examination, the
      exposure-response relationships for both allergens and for each outcome rose
      steeply at low levels of exposure and were attenuated at high levels of exposure.
      These patterns were modified by paternal atopy and by birth order. CONCLUSIONS:
      There are no linear relationships between early allergen exposure and the
      induction of childhood respiratory allergy; rather, the risks of IgE
      sensitisation and asthma rise at very low levels of exposure and are attenuated
      thereafter. These patterns are influenced by parental atopy and birth order.
      These findings suggest important gene-environment interactions in the development
      of atopy and asthma and imply that reductions in domestic allergen exposure alone
      are unlikely to have a major impact in decreasing the incidence of these diseases
      in childhood.

PMID- 15454652
TI  - Airway inflammation in children with difficult asthma: relationships with airflow
      limitation and persistent symptoms.
AB  - BACKGROUND: The effective management and development of new treatments for
      children with difficult asthma requires investigation of the underlying airway
      pathology and its relationships with persistent symptoms and airflow limitation.
      METHODS: The density of immunologically distinct inflammatory cells and cells
      expressing interleukin (IL)-4, IL-5, and RANTES was determined in paraffin
      embedded endobronchial biopsy specimens from 27 children with difficult asthma (6
      16 years) following treatment with systemic corticosteroids. Eleven non-asthmatic
      children (7-16 years) acted as controls. Reticular basement membrane (RBM)
      thickness was also recorded and forced expiratory volume in 1 second (FEV(1)) and
      exhaled nitric oxide (FE(NO)) measured, the latter in asthmatic children only.
      RESULTS: RBM thickness was greater in the asthmatic than the control group
      (median (range) 7.4 (3.1-11.1) v 5.1 (3.5-7.5) microm, p = 0.02). No other
      significant tissue difference was seen, nor was there a difference between
      asthmatic subjects with daily symptoms after systemic corticosteroids and those
      who became asymptomatic. CD4+ T lymphocyte density was higher in asthmatic
      subjects with persistent airflow limitation (post-bronchodilator FEV(1)<80%
      predicted) than in those without (9.1 (5.5-13.6) v 3.5 (0.6-34.9)%, p = 0.027).
      Analysing all asthmatic subjects together, there were negative correlations
      between CD4+ T lymphocytes and both pre-bronchodilator FEV(1) (r = -0.57 (95% CI 
      0.79 to -0.23), p = 0.002) and post-bronchodilator FEV(1) (r = -0.61 (95% CI 
      0.81 to -0.29), p<0.001). There were no significant correlations between FE(NO)
      and inflammatory cells of any type. CONCLUSION: In children with difficult asthma
      treated with systemic corticosteroids, persistent airflow limitation is
      associated with a greater density of CD4+ T lymphocytes in endobronchial biopsy
      specimens.

PMID- 15454653
TI  - Soluble CD86 protein in serum samples of patients with asthma.
AB  - BACKGROUND: Previous studies have reported that soluble (s) CD86 is involved in
      the initiation of the immune response. A study was undertaken to investigate the
      concentrations of sCD86 in serum samples from patients with bronchial asthma and
      to determine the cell origin of sCD86. METHODS: Serum sCD86 concentrations were
      measured in 52 asthmatic subjects and 25 non-atopic normal volunteers using an
      enzyme linked immunosorbent assay, and the relationship of serum sCD86
      concentrations to asthma severity and to total and differential white cell counts
      was analysed. Each type of white blood cell was purified and cultured in vitro to
      determine the cell origin of serum sCD86. RESULTS: Serum samples from patients
      with an acute asthma exacerbation had much higher levels of sCD86 (585.4 (20.5)
      IU/ml) than those from stable asthmatics (479.6 (15.7) IU/ml, p<0.001) and
      healthy individuals (435.1 (13.8) IU/ml, p<0.001), and there was no difference
      between the latter two groups (p = 0.079). In asthmatic subjects the serum sCD86
      level was inversely correlated with airway responsiveness, forced expiratory
      volume in 1 second, and with arterial carbon dioxide tension. In addition, the
      serum sCD86 level was positively correlated with numbers of lymphocytes,
      eosinophils, monocytes, but not neutrophils. The in vitro experiments indicated
      that sCD86 was produced by monocytes. CONCLUSIONS: The serum sCD86 protein level
      was significantly increased in asthmatic subjects during an exacerbation and
      correlated with the severity of asthma. sCD86 is most probably derived from
      monocytes in the peripheral blood.

PMID- 15454654
TI  - Linkage/association study of a locus modulating total serum IgE on chromosome
      14q13-24 in families with asthma.
AB  - BACKGROUND: A study was undertaken to validate a locus modulating total serum IgE
      levels on 14q13-24. METHODS: A linkage and association study was performed
      between total serum IgE and a panel of seven microsatellites which map to the
      14q13-24 region in 69 families with asthma recruited from Leeds, UK. RESULTS: Non
      parametric, multipoint, sib pair analysis showed no evidence of genetic linkage
      between the quantitative trait "log IgE" and any of the tested markers. However,
      a significant association was observed between locus D14S63 (14q23) and total
      serum IgE (p = 0.017). Allelic analysis showed an association between low total
      IgE and allele 157 of D14S63 (p = 0.01, OR = 0.63, 95% CI 0.44 to 0.90).
      Modelling of allele 157 genotypes as a continuous covariate indicated evidence of
      a significant inverse linear trend across the three genotypes where 157
      homozygotes had the lowest mean log IgE (p = 0.045). Association of D14S63 with
      log IgE was confirmed in the analysis of a combined dataset of 53 families from
      Southampton, UK and the 69 families from Leeds (total 122 families). An
      association was observed at the locus level (p = 0.022) and the allelic level
      where allele 165 showed an association with high total IgE (p = 0.001, OR = 3.79,
      95% CI 1.54 to 9.7) and allele 157 showed an association with low total IgE (p =
      0.041, OR = 0.77, 95% CI 0.6 to 0.99). The transmission disequilibrium test was
      positive for allele 165 (p<0.05) and negative for allele 157 (p>0.05).
      CONCLUSIONS: Despite the lack of linkage, the findings of this study support the
      previous observation of a gene(s) at 14q23 that modulates total serum IgE.

PMID- 15454655
TI  - Operating characteristics of the negative expiratory pressure technique in
      predicting obstructive sleep apnoea syndrome in snoring patients.
AB  - BACKGROUND: This study examines the operating characteristics of the expiratory
      flow response to a negative pressure (NEP) applied to the mouth in the prediction
      of obstructive sleep apnoea syndrome (OSAS) in snoring patients. METHODS: Two
      hundred and thirty eight patients with normal spirometric values were studied.
      Full laboratory polysomnography was performed and an NEP of -5 cm H(2)O was
      applied in the sitting and supine positions. RESULTS: A significant correlation
      was found between the degree of flow limitation measured by NEP in both positions
      (expressed as the percentage of the expired tidal volume over which NEP induced
      flow did not exceed spontaneous flow) and the apnoea-hypopnoea index (AHI). This
      correlation was significantly higher in the supine position (p<0.0001) where an
      expiratory flow limitation cut off value of >/=27.5% of the tidal volume produced
      a sensitivity of 81.9% and a specificity of 69.1% in predicting OSAS. CONCLUSION:
      These findings show that the degree of instability of the upper airway measured
      by NEP is correlated with the severity of OSAS. NEP had moderate sensitivity and
      specificity and may be useful in predicting OSAS in a clinic based population.

PMID- 15454656
TI  - Six month radiological and physiological outcomes in severe acute respiratory
      syndrome (SARS) survivors.
AB  - BACKGROUND: The long term physiological and radiological outcomes of SARS
      survivors and their possible determinants are uncertain. METHODS: SARS survivors
      in a follow up clinic in a regional hospital underwent high resolution computed
      tomography (HRCT) of the thorax and lung function tests 6 months after admission
      to hospital. The associations between the clinical and demographic data of the
      patients and the physiological and radiological outcomes were examined. RESULTS:
      Fifty seven patients took part in the study. Lung function abnormalities were
      detected in 43 patients (75.4%), with restrictive defects (n = 16) being most
      common (28.1%). Radiological abnormalities of any degree were detected in 43
      patients (75.4%). Only the use of pulse corticosteroids was associated with the
      presence of CT abnormalities (p = 0.043, OR 6.65, 95% CI 1.06 to 41.73).
      CONCLUSIONS: Physiological and radiological abnormalities are still present in a
      considerable proportion of SARS survivors at 6 months.

PMID- 15454657
TI  - Association of bronchial hyperresponsiveness and lung function with C-reactive
      protein (CRP): a population based study.
AB  - BACKGROUND: C-reactive protein (CRP), a marker of systemic inflammation, is a
      powerful predictor of adverse cardiovascular events. Respiratory impairment is
      also associated with cardiovascular risk. Although some studies have found an
      inverse relationship between lung function and markers of systemic inflammation,
      only one study has reported a relationship between lung function and CRP levels.
      In contrast, little is known about the relationship between bronchial
      hyperresponsiveness (BHR) and systemic inflammation. The association between lung
      function and CRP and between BHR and CRP has been investigated. METHODS: As part
      of the European Community Respiratory Health Survey follow up study serum CRP
      levels, forced expiratory volume in 1 second (FEV(1)), and BHR to methacholine
      (>/=20% decrease in FEV(1) to <4 mg methacholine) were measured in 259 adults
      aged 28-56 years free of cardiovascular disease or respiratory infection.
      RESULTS: Mean (SD) FEV(1) (adjusted for age, sex, height, and smoking status) was
      lower in subjects with a high CRP level (high tertile) (3.29 (0.44) l/s v 3.50
      (0.44) l/s; p<0.001) and BHR was more frequent (41.9% v 24.9%; p = 0.005) than in
      subjects with lower CRP levels (low+middle tertiles). Similar results were
      obtained when the potential confounding factors were taken into account. Similar
      patterns of results were found in non-smokers and in non-asthmatic subjects.
      CONCLUSIONS: Increased CRP levels are strongly and independently associated with
      respiratory impairment and more frequent BHR. These results suggest that both
      respiratory impairment and BHR are associated with a systemic inflammatory
      process.

PMID- 15454658
TI  - Respiratory health status of Australian veterans of the 1991 Gulf War and the
      effects of exposure to oil fire smoke and dust storms.
AB  - BACKGROUND: Since the 1991 Gulf War concerns have been raised about the effects
      on veterans' health of exposures to Kuwaiti oil fire smoke and to dust storms.
      METHODS: A cross sectional study compared 1456 Australian Gulf War veterans with
      a randomly sampled military comparison group (n = 1588). A postal questionnaire
      asked about respiratory conditions, exposures, medications, tobacco use,
      demographic characteristics, and military service details. During a medical
      assessment, spirometric tests and a physical examination were performed and a
      respiratory questionnaire was administered. RESULTS: The response rate for the
      Gulf War veteran group was 80.5% and for the comparison group 56.8%. Australian
      Gulf War veterans had a higher than expected prevalence of respiratory symptoms
      and respiratory conditions suggesting asthma (OR 1.4; 95% CI 1.1 to 1.9) and
      bronchitis first diagnosed since the Gulf War (OR 1.9; 95% CI 1.2 to 3.1) but did
      not have poorer lung function or more ventilatory abnormalities than the
      comparison group. Veterans who reported exposure to oil fire smoke had slightly
      poorer forced vital capacity (difference between means -0.10 l; 95% CI -0.18 to 
      0.03) and those exposed to dust storms had a slightly better peak expiratory flow
      rate (difference between means 12.0 l/min; 95% CI 0.6 to 23.4) than veterans who
      did not report exposure. Veterans who were in the Gulf at or after the start of
      the oil fires had more respiratory conditions suggesting asthma (OR 1.7; 95% CI
      1.0 to 2.9) than those who completed their deployment before this time.
      CONCLUSIONS: Increased self-reporting of respiratory symptoms, asthma, and
      bronchitis by veterans was not reflected in poorer lung function. The findings do
      not suggest major long term sequelae of exposure to oil fire smoke or dust
      storms.

PMID- 15454660
TI  - Respiratory bronchiolitis associated interstitial lung disease (RB-ILD): a case
      of an acute presentation.
AB  - Respiratory bronchiolitis associated interstitial lung disease (RB-ILD) is a
      recently described clinicopathological entity that occurs almost exclusively in
      current heavy cigarette smokers. Few cases have been reported in the literature
      and no studies have been carried out on the effect of treatment, which currently
      consists of smoking cessation with or without corticosteroids. We report the
      first case of an acute presentation of histologically proven RB-ILD in a young
      cigarette smoker whose diagnosis and management proved to be difficult. Smoking
      cessation alone was found to be inadequate so management was combined with
      corticosteroid therapy.

PMID- 15454659
TI  - alpha1-Antitrypsin deficiency . 6: new and emerging treatments for alpha1
      antitrypsin deficiency.
AB  - Alpha-1-antitrypsin (AAT) deficiency is a genetic condition that increases the
      risk of developing lung and liver disease, as well as other associated
      conditions. Most treatment of affected individuals is not specifically directed
      at AAT deficiency but focuses on the resultant disease state. The only currently
      available specific therapeutic agent-namely, intravenous augmentation with plasma
      derived AAT protein-is marketed in a limited number of countries. Treatments
      aimed at correcting the underlying genetic abnormality, supplementing or
      modifying the gene product, and halting or reversing organ injury are now
      beginning to emerge. These innovative approaches may prove effective at modifying
      or eliminating diseases association with AAT deficiency.

PMID- 15454661
TI  - A rare presentation of a ruptured bronchial artery aneurysm.

PMID- 15454662
TI  - Introduction to stroke genomics.
AB  - Translation of the explosion in knowledge of acute ischemic stroke into
      satisfactory treatment regimens has yet to happen. At present tPA, intra-arterial
      prourokinase and low-molecular-weight heparin form the vanguard for therapeutic
      intervention, yet these treatments have a limited therapeutic window. Part of
      this expansion in understanding has been driven by the contribution of stroke
      genetics and genomics. However, despite the enormous preclinical and clinical
      information of receptors, enzymes, second messenger systems, and so forth, that
      are implicated in stroke pathophysiology, delivery of novel drug treatment has
      been slow. This introductory chapter discusses the multiple sources of clinical
      and preclinical genetic information. It will describe the importance of
      integrating expression information into multiple preclinical models with temporal
      and spatial roles in lesion pathology and, furthermore developing an
      understanding of function in the clinic before claiming a role in ischemic
      stroke. The goal of such a holistic integration of information is to increase the
      yield from current datasets of gene expression and ultimately to help expand the
      choice of treatment available to the physician and patient.

PMID- 15454663
TI  - Choice, methodology, and characterization of focal ischemic stroke models: the
      search for clinical relevance.
AB  - To develop novel neuroprotective or neurorestorative agents for clinical
      application, the appropriate selection and characterization of preclinical focal
      stroke models is required to provide confidence in predicting therapeutic
      efficacy. Compelling evidence for novel therapies derived from the pathological
      and functional consequences of models of cerebral ischemia in the rat (and higher
      species) is an essential prerequisite before large expensive clinical trials are
      begun. This chapter provides an overview of focal ischemic models, with an
      emphasis on objective functional assessment of pathological mechanisms and
      efficacy of novel therapeutic strategies. The ability to predict functional
      consequences from structural abnormalities is a critical theme that can be
      extrapolated from the preclinical to the clinical setting, in that certain brain
      regions are inextricably linked to specific behavioral functions. This underlying
      approach is highly relevant, as monitoring the dynamic pathological and
      functional changes attributed to focal stroke will reveal new insights into novel
      mechanisms and targets that play a role in the evolution of cell death and
      impaired function. The utility of novel genomic technologies that are aligned
      with methods to determine structure-function relationships in preclinical models
      will facilitate a greater understanding of the pathophysiological process and
      potentially generate new targets that may ultimately be used to predict or offer
      clinical benefit.

PMID- 15454664
TI  - Mutant animal models of stroke and gene expression: the stroke-prone
      spontaneously hypertensive rat.
AB  - The recent completion of the Human Genome Project provides the potential to
      advance our knowledge of pathogenesis and identify the gene(s) associated with
      particular diseases. However, using human DNA to correlate individual genomic
      variations with particular disorders such as stroke will be extremely challenging
      because of the large number of variables within an individual, and across
      different populations. Mutant animal models of stroke such as the stroke-prone
      spontaneously hypertensive rat (SHRSP) provide the scientist with genetic
      homogeneity, not possible within a human population, to aid our search for
      causative genes. This chapter describes the methods our group have employed to
      study the genetic heritability of stroke sensitivity in the SHRSP. Sections are
      included on quantitative trait loci, mapping, and congenic strain construction
      for the identification of genetic determinants of stroke sensitivity in the
      SHRSP.

PMID- 15454665
TI  - Gene therapy in neurological disease.
AB  - Advances in the area of stroke and other neurodegenerative disorders have
      identified a variety of molecular targets for potential therapeutic intervention.
      The use of modified viral vectors has now made it possible to introduce foreign
      DNA into central nervous system cells, permitting overexpression of the protein
      of interest. A particular advantage of the herpes simplex system is that the
      herpes virus is neurotropic and is therefore suited for gene therapy to the
      nervous system. The vectors used by our group to date utilize an amplicon-based
      bipromoter system, which permits expression of both the gene of interest and a
      reporter gene. Using this strategy, we have been successful in transferring
      potentially neuroprotective genes to individual central nervous system cells.
      Using this approach, it is possible to show that gene therapy both before and
      after insult is feasible. Some limitations of this technique exist, the main one
      being delivery and extent of transfection. Although application to clinical
      stroke is probably remote, viral vector-mediated gene therapy provides a unique
      and powerful tool in the study of molecular mechanisms involved in brain injury.

PMID- 15454666
TI  - Stem cell transplantation after middle cerebral artery occlusion.
AB  - Stem cell lines have been and are being developed to treat damage in the central
      nervous system after stroke. Stem cells are able to migrate to areas of damage
      and to differentiate into neurons and glia. Grafts of murine stem cells have been
      shown to promote recovery from behavioral dysfunction after stroke. We have
      developed protocols to optimize behavioral testing, animal recovery, and stem
      cell delivery after middle cerebral artery occlusion. In this chapter we discuss
      study protocols aimed at integrating in vitro preparation of cells, small animal
      surgery, behavioral testing batteries, and histological analysis.

PMID- 15454667
TI  - Endogenous brain protection: models, gene expression, and mechanisms.
AB  - Almost all injurious stimuli, when applied below the threshold of producing
      injury, activate endogenous protective mechanisms that significantly decrease the
      degree of injury after subsequent injurious stimuli. For example, a short
      duration of ischemia (i.e., ischemic preconditioning [PC]) can provide
      significant brain protection to subsequent long-duration ischemia (i.e., ischemic
      tolerance [IT]). PC/IT has recently been shown in human brain, suggesting that
      learning more about these endogenous neuroprotective mechanisms could help
      identify new approaches to treat patients with stroke and other central nervous
      system disorders/injury. This chapter provides a brief overview of PC/IT
      research, illustrates the types of data that can be generated from in vivo and in
      vitro models to help us understand gene and protein expression related to induced
      neuroprotective mechanisms, and emphasizes the importance of future research on
      this phenomenon to help discover new mechanisms and targets for the medical
      treatment of brain and other end-organ injuries.

PMID- 15454668
TI  - Production of transgenic and mutant mouse models.
AB  - Manipulation of the rodent genome by deliberately inserting (transgenic) or
      removing (knockout) a gene of interest or indeed by selectively breeding animals
      with a spontaneous or random mutation producing a trait of interest has been
      developed over several years. Mouse "fanciers" have been selectively breeding
      interesting mice since the turn of the last century to produce a plethora of
      different background strains of the common house mouse (Mus musculus). Rat
      (Rattus norvegicus) strain development has also proceeded with selective
      breeding, although the range of strains is more limited. The deliberate and
      targeted manipulation of the mouse genome has been with us for over two decades,
      with the rat genome a more recent addition, and yet this technology has been
      limited to a very narrow range of genes. With the complete mapping of the mouse
      genome (and the rat genome soon to follow), the powerful techniques of transgenic
      and knockout rodent production can be applied to the numerous genes whose
      expression is altered in existing stroke models.

PMID- 15454669
TI  - 3-nitropropionic acid model of metabolic stress: assessment by magnetic resonance
      imaging.
AB  - 3-Nitropropionic acid (3-NPA) is a potent mitochondrial inhibitor that can be
      administered systemically to create a progressive and localized striatal
      neurodegeneration mimicking many of the pathological features of Huntington's
      disease and other forms of metabolic compromise such as cerebral ischemia, carbon
      monoxide poisoning, and hypoglycemia. Here we describe a method to produce 3-NPA
      induced lesions using the systemically administered toxin. We also describe
      magnetic resonance imaging methods to allow assessment of lesion severity over
      time within the same animal.

PMID- 15454670
TI  - Practicalities of genetic studies in human stroke.
AB  - Considerable evidence suggests genetic factors are important in the pathogenesis
      of multifactorial stroke. However, studies identifying the underlying genes have
      been largely disappointing. This chapter reviews the different approaches and
      their relative merits. It is likely stroke is a polygenic disorder and that
      underlying genes may interact within environmental risk factors. Stroke itself is
      a syndrome caused by a number of different pathologies, which may result from
      different genetic predispositions. Therefore accurate stroke subtyping is likely
      to be important in identifying genetic associations. Previous studies have
      suffered from small sample size, lack of adequate phenotyping, and poor case
      control matching. The most popular approach to identifying genes in human
      polygenic ischemic stroke has been the candidate gene approach. The relative
      merits of this approach are discussed. More recently this has been extended to
      family-based association studies. Linkage-based approaches have been used less
      although current studies are implementing the affected-sibling-pair method. In
      the future genome-wide association studies are likely to become more widely used.

PMID- 15454671
TI  - Evaluation of the interactions of common genetic mutations in stroke.
AB  - Stroke is a common entity. It is the third leading cause of death and the leading
      cause of adult disability in the developed world. More than 110 heritable
      disorders, more than 175 genetic loci, and more than 2050 unique mutations
      predisposing to stroke are known. Although ischemic stroke can result from merely
      one gene defect (and a number of clearly defined mendelian hereditary disorders
      do lead to stroke), the interaction of unfavorable genetic factors such as the
      Leiden V, methylenetetrahydrofolate reductase (MTHFR) 677TT, apolipoprotein E
      (ApoE) 4, and angiotensin-converting enzyme (ACE) D/D genotypes, which alone are
      not major risk factors, can in specific patterns exert a synergistic effect on
      certain clinical risk factors. This chapter discusses how to evaluate these
      interactions and the interpretation of findings.

PMID- 15454672
TI  - Technologies of disease-related gene discovery using preclinical models of
      stroke.
AB  - Stroke is a clinically defined neurological syndrome characterized by rapidly
      progressing symptoms and signs of focal loss of cerebral function. The
      initiation, propagation, and maturation of ischemic stroke are associated with de
      novo expression of multiple genes in endogenous brain tissues and infiltrated
      inflammatory cells. This chapter provides an overview for the use of state-of-the
      art molecular biological approaches to investigate de novo gene expression in
      animal models of focal stroke, including subtractive cDNA library screening, mRNA
      differential display, suppression subtractive hybridization, representational
      difference analysis, serial analysis of gene expression, and microarrays.
      Identification of stroke-related gene expression will facilitate the
      understanding of the molecular basis of stroke pathogenesis and may provide a
      novel therapeutic intervention of the disease.

PMID- 15454673
TI  - Quantitative analysis of gene transcription in stroke models using real-time RT
      PCR.
AB  - Many researchers have sought to study changes in gene expression in preclinical
      models of stroke. These range from in vitro models of ischemia, neuronal death,
      and regeneration to in vivo animal models aimed at replicating pathologies and
      regenerative processes typical of the clinical situation. In all such models,
      changes in gene expression occur, which may be assessed by measuring the
      abundance of the mRNA transcribed from particular genes of interest. The advent
      of real-time reverse-transcriptase polymerase chain reaction (RT-PCR) has vastly
      improved the sensitivity and accuracy of mRNA detection and is now the method of
      choice in many studies. Although this is a relatively simple and rapid technique,
      it has a number of pitfalls, especially in experimental design and data analysis.
      In this chapter we describe a detailed experimental protocol for real-time RT-PCR
      detection of mRNA transcripts, as used in the rat permanent middle cerebral
      artery occlusion model. We also discuss methods for analysis and interpretation
      of the resulting data.

PMID- 15454674
TI  - Effective analysis of genomic data.
AB  - High-throughput biotechnology has enabled genome-wide investigation of gene
      expression and has the potential to identify genes that have a role to play in
      focal cerebral ischemia, as well as many other interventions. The advent of this
      technology has also led to the generation of large amounts of expensive and
      complex expression data. One of the major problems with the generation of so much
      data is locating and extracting the relevant information to aid target
      identification and interpretation effectively and reliably. Statistical
      involvement is vital. Not only does it help to ensure effective extraction of
      information from the data, it also increases the likelihood that the data
      collected will embody the information about the differential expression of
      interest in the first place. The goal of this chapter is to recommend an
      effective process for investigating gene expression data. There are five stages
      in this process that we believe lead to reliable results when routinely applied
      to an expression dataset, once it has been appropriately generated and collected:
      (1) biological problem definition and design selection; (2) data examination,
      "preprocessing," and reexamination; (3) data analysis step I: screening for
      differentially expressed genes; (4) data analysis step II: verifying differential
      expression; and (5) biological verification, interpretation, and communication.

PMID- 15454675
TI  - Bioinformatic approaches to assigning protein function from novel sequence data.
AB  - The current pace of functional genomic initiatives and genome sequencing projects
      has provided researchers with a bewildering array of sequence and biological data
      to analyze. The disease system-driven approach to identifying key genes
      frequently identifies nucleotide and protein sequences for which the gene and
      protein function are not known in sufficient detail to allow informed follow-up.
      Using a range of bioinformatic tools and sequence-based clues, most of unassigned
      sequences can now be annotated. This chapter takes as an example an unannotated
      expressed sequence tag, describing how to identify its related gene, and how to
      annotate the encoded protein using sequence, profile, and structure-based
      annotation methodologies.

PMID- 15454676
TI  - Pragmatic target discovery from novel gene to functionally defined drug target:
      the interleukin-1 story.
AB  - The pro-inflammatory cytokine interleukin-1 (IL-1) has been proposed as a
      mediator of the acute neurodegenerative changes that occur following stroke. This
      is based largely on experimental studies in rodents, in particular the marked
      reduction in ischemic cell death seen when IL-1 receptor antagonist (IL-1ra) is
      administered. Mechanisms of IL-1 action remain largely unknown, but they may
      involve complex effects on many cells including microglia, astrocytes, neurons,
      and endothelial cells. In light of this, IL-1ra is currently under consideration
      as a potential treatment for stroke and other neurodegenerative conditions.

PMID- 15454677
TI  - Selecting appropriate animal models and experimental designs for endocrine
      disruptor research and testing studies.
AB  - Evidence that chemicals in the environment may cause developmental and
      reproductive abnormalities in fish and wildlife by disrupting normal endocrine
      functions has increased concern about potential adverse human health effects from
      such chemicals. US laws have now been enacted that require the US Environmental
      Protection Agency (EPA) to develop and validate a screening program to identify
      chemicals in food and water with potential endocrine-disrupting activity. EPA
      subsequently proposed an Endocrine Disruptor Screening Program that uses in vitro
      and in vivo test systems to identify chemicals that may adversely affect humans
      and ecologically important animal species. However, the endocrine system can be
      readily modulated by many experimental factors, including diet and the genetic
      background of the selected animal strain or stock. It is therefore desirable to
      minimize or avoid factors that cause or contribute to experimental variation in
      endocrine disruptor research and testing studies. Standard laboratory animal
      diets contain high and variable levels of phytoestrogens, which can modulate
      physiologic and behavioral responses similar to both endogenous estrogen as well
      as exogenous estrogenic chemicals. Other studies have determined that some
      commonly used outbred mice and rats are less responsive to estrogenic substances
      than certain inbred mouse and rat strains for various estrogen-sensitive
      endpoints. It is therefore critical to select appropriate biological models and
      diets for endocrine disruptor studies that provide optimal sensitivity and
      specificity to accomplish the research or testing objectives. An introduction is
      provided to 11 other papers in this issue that review these and other important
      laboratory animal experimental design considerations in greater detail, and that
      review laboratory animal and in vitro models currently being used or evaluated
      for endocrine disruptor research and testing. Selection of appropriate animal
      models and experimental design parameters for endocrine disruptor research and
      testing will minimize confounding experimental variables, increase the likelihood
      of replicable experimental results, and contribute to more reliable and relevant
      test systems.

PMID- 15454678
TI  - Commentary: setting aside tradition when dealing with endocrine disruptors.
AB  - In 1996, the US Congress directed the Environmental Protection Agency to produce
      screens and assays to detect estrogenic and other endocrine-disrupting chemicals
      in food and water. To date, there are none. Years have been wasted in attempts to
      utilize traditional toxicological approaches to solve the problem, when in
      retrospect, it is now apparent that the delay in part stems from the reluctance
      to attack the problem with entirely new approaches. To develop new testing
      protocols, it is necessary to set aside much of the dogma of toxicology and to
      begin again with open minds. A few pertinent examples are provided concerning
      what has been overlooked and what needs to be done. In particular, it is
      necessary to give close attention to the selection of animal strain and diet,
      factors that were only loosely controlled historically when one takes into
      consideration what has been learned in the last decade. Vast numbers of animals
      have been sacrificed, and more will be sacrificed, in futile attempts to validate
      assays and to develop safety standards unless knowledge gained over the past
      decade concerning the sensitivity and complexity of the endocrine system is taken
      into consideration.

PMID- 15454679
TI  - Selecting the appropriate rodent diet for endocrine disruptor research and
      testing studies.
AB  - Selecting the optimum diet for endocrine disruptor (ED) research and testing
      studies in rodents is critical because the diet may determine the sensitivity to
      detect or properly evaluate an ED compound. Dietary estrogens can profoundly
      influence many molecular and cellular event actions on estrogen receptors and
      estrogen-sensitive genes. The source, concentration, relative potency, and
      significance of dietary estrogens in rodent diets are reviewed, including dietary
      factors that focus specifically on total metabolizable energy and phytoestrogen
      content, which potentially affect ED studies in rodents. Research efforts to
      determine dietary factors in commercially available rodent diets that affect
      uterotrophic assays and the time of vaginal opening in immature CD-1 mice are
      summarized. A checklist is provided of important factors to consider when
      selecting diets for ED research and testing studies in rodents. Specific
      metabolizable energy levels are recommended for particular bioassays. Discussions
      include the between-batch variation in content of the phytoestrogens daidzein and
      genistein, the effects of total metabolizable energy and phytoestrogens on the
      timing (i.e., acceleration) of vaginal opening, and increased uterine weight in
      immature CD-1 mice. It is concluded that rodent diets differ significantly in
      estrogenic activity primarily due to the large variations in phytoestrogen
      content; therefore animal diets used in all ED studies should ideally be free of
      endocrine-modulating compounds.

PMID- 15454680
TI  - Laboratory animal science issues in the design and conduct of studies with
      endocrine-active compounds.
AB  - The use of rodent models for research and testing on endocrine-active compounds
      necessitates an awareness of a number of laboratory animal science issues to
      standardize bioassay methods and facilitate reproducibility of results between
      laboratories. These issues are not unique to endocrine research but are
      particularly important in this field due to the complexities and
      interdependencies of the endocrine system, coupled with the inherently sensitive
      and variable nature of physiological endpoints. Standardization of animal models
      and the control of animal environments depend on the establishment of strong
      scientific partnerships between research investigators and laboratory animal
      scientists. Laboratory animal care and use programs are becoming increasingly
      complex and are constantly changing, fueled in part by technological advances,
      changes in regulations concerning animal care and use, and economic pressures.
      Since the early 1980s, many institutions have moved to centralization of animal
      facility operations concomitant with numerous changes in housing systems, barrier
      concepts, equipment, and engineering controls of the macro- and microenvironment.
      These and other changes can have an impact on animals and the conduct of
      endocrine experiments. Despite the potential impact of animal care and use
      procedures on research endpoints, many investigators are surprisingly naive to
      the animal facility conditions that can affect in vivo studies. Several key
      animal care and use issues that are important to consider in endocrine
      experiments with rodent models are described.

PMID- 15454681
TI  - Use of the laboratory rat as a model in endocrine disruptor screening and
      testing.
AB  - The screening and testing program the US Environmental Protection Agency (EPA) is
      currently developing to detect endocrine-disrupting chemicals (EDCs) is
      described. EDCs have been shown to alter the following activities: hypothalamic
      pituitary-gonadal (HPG) function; estrogen, androgen, and thyroid hormone
      synthesis; and androgen and estrogen receptor-mediated effects in mammals and
      other animals. The value and limitations of mammalian in vivo assays are
      described that involve the use of the laboratory rat, the EPA Endocrine Disruptor
      Screening and Testing Advisory Committee species of choice. The discussion
      includes the evaluation of high-priority chemicals positive in the Tier 1
      Screening (T1S) battery, and of subsequent testing in the Tier 2 (T2) battery,
      with additional short-term screening assays proposed for use in T1.5 to eliminate
      any uncertainty about T1S results. Descriptions include the in vivo uterotropic
      assay, which detects estrogens and antiestrogens; the pubertal female assay,
      which assesses steroidogenesis, antithyroid activity, antiestrogenicity, and HPG
      function; and the Hershberger assay, which detects the weight of androgen
      dependent tissues in castrate-immature-male rats (antiandrogens). Of the several
      alternative mammalian in vivo assays proposed, a short-term pubertal male rat
      assay appears most promising for inclusion in T1 or T1.5. An additional in utero
      lactational screening protocol is being evaluated, but appears to be better
      suited for T1.5 or T2 due to the size, complexity, and duration of the assay. The
      adult intact male assay, also proposed as an alternative for T1, attempts to
      identify EDCs in a hormonal battery, but has limited value as a screen due to
      lack of sensitivity and specificity. For Tier 2 testing, the number of endocrine
      sensitive endpoints and offspring (F1) examined in multigenerational tests must
      be thoughtfully expanded for EDCs on a mode-of-action-specific basis, with
      consideration given to tailoring T2 based on the results of T1S.

PMID- 15454682
TI  - Animal models and studies of in utero endocrine disruptor effects.
AB  - The rate of organ and system development in mammals, including humans, is most
      rapid during the prenatal period. Perturbations of the endocrine system during
      this period can have profound effects on later anatomy, physiology, behavior, and
      the onset of disease. Endocrine-disrupting compounds can cause perturbations
      during fetal development by mimicking or blocking natural hormones. In
      experimental studies, compounds that mimic estrogens and those that block
      androgen action have been shown to have a number of long-term effects. Among
      these effects are the acceleration of puberty onset, increased incidence of adult
      cancers such as vaginal and prostate cancers, and alterations in sexually
      dimorphic anatomy, physiology, and behavior. Laboratory animal models continue to
      play a crucial role in identifying endocrine disruptors, determining their mode
      of action, and demonstrating their consequences.

PMID- 15454683
TI  - Behavioral effects of endocrine-disrupting substances: phytoestrogens.
AB  - A major source of endocrine-disrupting substances, usually not considered in
      laboratory animal experiments, is the diet used in research investigations. Soy
      represents the main protein source in almost all natural-ingredient commercially
      available formulated diets. Soy-derived isoflavones are the most abundant and in
      many ways the most studied phytoestrogens, and phytoestrogens (isoflavones) are
      known endocrine disruptors. Research is reviewed that identifies the
      physiological and behavioral endocrine-disrupting effects of dietary
      phytoestrogens (isoflavones) in animal diets, including most of the isoflavones,
      which are in a glycoside form and biologically inactive, and those in the
      gastrointestinal tract, which are biologically active. The isoflavones genistein
      and daidzein have similar molecular weights and structural characteristics to
      that of 17-beta estradiol, which may enable them to exert estrogenic and
      antiestrogenic properties are described and characterized. Daidzein can be
      further metabolized to the potent and abundant molecule equol, which in rodents
      is produced in very large amounts and represents the major circulating metabolite
      among all biologically active isoflavones. Equol has the unique and important
      ability to specifically bind 5 alpha-dihydro-testosterone, and to act in turn to
      inhibit the action of this potent androgen. The specific influence of dietary soy
      phytoestrogens on consumptive, learning and memory, and anxiety-related behaviors
      is identified. Regulatory behaviors such as food and water intake, adipose
      deposition and leptin, and insulin levels affected by dietary isoflavones are
      also discussed.

PMID- 15454684
TI  - Estrogen receptor knockout mice as a model for endocrine research.
AB  - The biological effects of estrogen in mammalian target tissues are important for
      multiple organ systems including the male and female reproductive tract and the
      neuroendocrine, skeletal, and cardiovascular systems. Numerous physiological
      effects of estradiol are modulated by the estrogen receptor (ER), a Class I
      member of the nuclear receptor superfamily. However, more recent studies have
      also implicated nongenomic effects of estrogen, which may involve a membrane
      binding site. The two forms of the ER are the classical estrogen receptor-alpha
      (ERalpha) and the more recently discovered estrogen receptor-beta (ERbeta). Gene
      targeting techniques were used to generate mice lacking either functional ERalpha
      (alphaERKO), ERbeta (betaERKO), or both ERs (alphabetaERKO) to provide a model
      for evaluating estrogen receptor action. These knockout models provide a unique
      tool to study the effects of estrogen in the context of the whole animal and to
      discern the role of each ER in various tissues. The reproductive phenotypes as
      well as some of the nonreproductive phenotypes of the different ERKO models are
      summarized.

PMID- 15454685
TI  - Factors considered in using birds for evaluating endocrine-disrupting chemicals.
AB  - Documented effects on fish and wildlife populations, coupled with evidence from
      human poisonings, epidemiology, and experimental toxicology, led to the formation
      of the Endocrine Disruptor Screening Program within the US Environmental
      Protection Agency. The main objectives of the program are to validate and
      implement the screens and tests that have been proposed for evaluating possible
      endocrine-disrupting activity of chemicals. An avian two-generation test is one
      of the recommended higher tier tests currently undergoing prevalidation. The
      advantages and disadvantages of the two species of quail considered as
      candidates, the northern bobwhite (Colinus virginianus) and the Japanese quail
      (Coturnix japonica), are described as well as the basis for final selection of
      the Japanese quail. Among the numerous considerations necessary for ultimately
      optimizing a two-generation test method using birds, the following key factors
      are discussed: the number of birds used in the test, when to begin exposure of
      the P generation, selection and exposure of the F1 generation, and endpoints.

PMID- 15454686
TI  - Small fish models for identifying and assessing the effects of endocrine
      disrupting chemicals.
AB  - Endocrine-disrupting chemicals (EDCs), particularly those that affect the
      hypothalamic-pituitary-gonadal (HPG) axis of vertebrates, have become a focus of
      regulatory screening and testing throughout the world. Small fish species,
      principally the fathead minnow (Pimephales promelas), Japanese medaka (Oryzias
      latipes), and zebrafish (Danio rerio), are used as model organisms for several of
      these testing programs. Fish are appropriate models for testing EDCs, not only
      from the perspective of existing ecological impacts, but also in terms of species
      extrapolation. Specifically, there is a significant degree of conservation of
      basic aspects of the HPG axis across vertebrates, which provides a technically
      robust basis for using results from fish tests to predict likely modes/mechanisms
      of action of potential EDCs in other vertebrates. Different experimental
      designs/endpoints for partial- and full-life cycle tests with fish that enable a
      consideration of a broad range of EDCs are described. Examples of results with
      specific chemicals in tests with the fathead minnow, medaka, and zebrafish are
      presented and discussed in terms of sensitivity and specificity for different
      classes of EDCs.

PMID- 15454687
TI  - Use and role of invertebrate models in endocrine disruptor research and testing.
AB  - Historically, invertebrates have been excellent models for studying endocrine
      systems and for testing toxic chemicals. Some invertebrate endocrine systems are
      well suited for testing chemicals and environmental media because of the ease of
      using certain species, their sensitivity to toxic chemicals, and the broad choice
      of models from which to choose. Such assays will be useful in identifying
      endocrine disruptors to protect invertebrate populations and as screening systems
      for vertebrates. Hormone systems are found in all animal phyla, although the most
      simple animals may have only rudimentary endocrine systems. Invertebrate
      endocrine systems use a variety of types of hormones, including steroids,
      peptides, simple amides, and terpenes. The most well-studied hormone systems are
      the molting and juvenile hormones in insects, the molting hormones in
      crustaceans, and several of the neurohormones in molluscs and arthropods. These
      groups offer several options for assays that may be useful for predicting
      endocrine disruption in invertebrates. A few invertebrate phyla offer predictive
      capabilities for understanding vertebrate endocrine-disrupting chemicals. The
      echinoderms, and to a lesser extent molluscs, have closer evolutionary
      relationships with the vertebrates than the arthropods and these phyla. The
      recently identified estrogen receptor structure within the genome of the marine
      gastropod, Aplysia, indicates that the estrogens, and probably the basic steroid
      receptor, are quite old evolutionarily. This review of the recent literature
      confirms the effects of some endocrine-disrupting chemicals on invertebrates-
      tributyltin on snails, pesticides on insects and crustaceans, and industrial
      compounds on marine animals.

PMID- 15454688
TI  - In vitro models in endocrine disruptor screening.
AB  - The public and scientific concern that chemicals present in the human diet and
      the environment and their ability to disrupt the normal hormonal milieu in humans
      and wildlife have become a high-profile international issue. In 1998, the
      Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC) convened by
      the Environmental Protection Agency (EPA) recommended a tiered testing approach
      for the evaluation of estrogen, androgen, and thyroid-related effects of some
      87,000 commercial chemicals and environmental contaminants. The function of this
      committee concluded with its final report, and the further implementation of the
      recommended testing strategy has now been carried forward with the assistance of
      the Endocrine Disruptor Methods Validation Subcommittee. The function of this
      body is to provide advice to the EPA on scientific and technical issues related
      specifically to the conduct of studies required for the validation of assays
      proposed by the EDSTAC as part of the tiered screening program. The EDSTAC
      recommended and alternative screening batteries encompass four in vitro mammalian
      assays. The current methodologies and validation status of the proposed in vitro
      EDSTAC assays are discussed and consist of estrogen/androgen receptor binding,
      estrogen/androgen gene transactivation, and minced testis, and one alternate
      (placental aromatase) in vitro screening assay.

PMID- 15454689
TI  - Documentation of immune profile of microglia through cell surface marker study in
      glioma model primed by a novel cell surface glycopeptide T11TS/SLFA-3.
AB  - STATEMENT OF THE PROBLEM: The sheep erythrocyte membrane glycoprotein T11TS/SLFA
      3 can form a ligand-receptor complex with CD2 present on immunocyte and exert
      stimuli for activation and proliferation. Regression of brain tumor with the
      application of T11TS indicates the probable role of microglia, the chief
      immunomodulatory cell within the brain compartment. In the present study
      microglial activation and immunophenotypic modulation were assessed in T11TS
      treated brain tumor-bearing animal models. Rat glioma models induced by chemical
      carcinogen ENU were treated with three consecutive doses of T11TS. Microglial
      cells from brain were isolated and assessed through E-rosette formation, SEM and
      FACS for CD2, MHC class II, CD25, and CD4. The preliminary indication of presence
      of CD2 on microglia through E-rosette formation was confirmed by SEM and FACS.
      MHC class II and CD2 single and double positive subpopulations exist, and their
      expression is also modulated in different doses of T11TS. A general trend of
      highest receptor saturation and microglial activation, measured through the
      activation marker CD25 and CD4 expression, was observed in 2nd dose of T11TS
      administration, which was then dampened via a complex immune feedback mechanism
      in the 3rd dose.

PMID- 15454690
TI  - Identification of receptors responsible for binding of the mannose specific
      lectin to the gut epithelial membrane of the target insects.
AB  - The sap-sucking homopteran insects, commonly known as aphids and leafhoppers are
      responsible for a huge amount of lost productivity of mustard, chickpea, cabbage,
      rice and many other important crops. Due to their unique feeding habits and
      ability to build up a huge population in a very short time, they are very
      difficult to control. The objective of the ongoing program is to develop insect
      resistant crop species through genetic engineering techniques to combat the yield
      losses, which necessitates the identification of appropriate control elements. In
      this direction, mannose-binding 25 kDa lectins have been purified from leaves of
      garlic, Diffenbachia sequina and tubers of Colocasia esculanta. The purified
      lectins have been analyzed in SDS-PAGE. The effectiveness of these lectins
      against chickpea aphids, mustard aphids and green leaf hoppers of rice have been
      tested. The LC(50) value of each lectin against different insects had been
      monitored [1,2]. Through immunolocalization analysis, the binding of the lectin
      had been demonstrated at the epithelial membrane of the midgut of the lectin
      treated insects [1]. Receptor proteins of brush border membrane vesicle (BBMV) of
      the target insects, responsible for binding of the lectin to the midgut of the
      epithelial layer have been purified and analyzed through ligand assay.
      Biochemical studies have been undertaken to investigate the lectin-receptor
      interaction at molecular level.

PMID- 15454691
TI  - Identification of 9-O-acetylated sialoglycans on peripheral blood mononuclear
      cells in Indian Visceral Leishmaniasis.
AB  - Although the existence of O -acetylated sialic acids is well known, it is only in
      recent years that steady refinement of analytical techniques have enabled
      detailed mapping of their structural diversity [1]. Fluorimetric analysis of
      peripheral blood mononuclear cells (PBMC) of patients with Visceral Leishmaniasis
      (VL) showed six fold increase in the percentage of surface 9-O-acetylated
      sialoglycoconjugates (9-O-AcSGs) as compared to normal human donors. Using
      Achatinin-H, a 9-O-acetyl sialic acid- binding lectin, an enhanced presence of 9
      O-AcSGs in an alpha2 --> 6 linkage was demonstrated by flow cytometry; abolition
      of its binding by pretreatment with a recombinant 9-O-acetylesterase corroborated
      the presence of this glycotope. Western blotting of PBMC from VL patients
      indicated the presence of five O-acetylated sialoglycans corresponding to 144,
      65, 56, 36 and 19 kDa as compared to 144 and 36 kDa in normal individuals. Taken
      together our data indicates that during active disease, there is an
      overexpression of 9AcSGs on the surface of PBMC of VL patients, thus opening up
      new research avenues wherein the expression of this biomarker could be exploited
      to monitor the clinical status of VL patients.

PMID- 15454692
TI  - Variations in binding characteristics of glycosylated human C-reactive proteins
      in different pathological conditions.
AB  - C-reactive protein (CRP) is a clinically important classic acute phase pentameric
      protein. It is thought to play an important role in immunomodulation. Earlier
      reports convincingly demonstrated that human CRP is differentially glycosylated
      in different pathological conditions. Although CRP is considered to be a
      clinically important molecule, changes in binding characteristics with
      appropriate ligands with respect to glycosylation remain unexplored. In an effort
      to demonstrate that these glycosylated molecular variants are capable of
      modulating their binding activity with different ligands, CRPs were affinity
      purified from six different clinical samples. Variable amounts of linkage
      specific sialic acid derivatives were found in these CRPs with varying tryptophan
      contents. Differential binding patterns with antibodies against human CRP, human
      IgG, and other ligands like fibronectin, fetuin, and asialofetuin indicated that
      the purified CRPs differed significantly in their lectin-like interactions. Thus,
      we have convincingly demonstrated that differentially induced CRPs exhibited
      variable binding characteristics. These results may have far reaching practical
      applications for understanding acute phase responses.

PMID- 15454693
TI  - Prediction of 3-D structures of fucose-binding proteins and structural analysis
      of their interaction with ligands.
AB  - The importance of fucose-binding proteins stems from the presence of fucose as
      terminal sugars in H and Lewis (a) blood groups. Recently, the structure of a
      complex between Anguilla anguilla agglutinin (AAA) and alpha-L-fucose has been
      worked out at 1.9 A resolution. The structure of AAA characterizes the novel fold
      of an entire lectin family. In the present study, molecular modeling techniques
      have been used to identify new proteins that can provide a similar fucose binding
      module in the newly discovered genomic sequences using the above mentioned
      structural information. We modeled 3-D structures of three such proteins, namely,
      ebiP5322 protein of Anopheles gambiae, a pentraxin of Xenopus laevis, and the fw
      gene product of Drosophila melanogaster. alpha-L-fucose was docked in the binding
      pockets of the modeled structures followed by energy minimization and molecular
      dynamic runs to obtain the most probable structures of the complexes. Properties
      of these modeled complexes were studied to examine the nature of physicochemical
      forces involved in the complex formation and compared with AAA-alpha-L-fucose
      complex. It was found that ebiP5322 protein of A. gambiae and the pentraxin of X.
      laevis can provide a fucose-binding fold similar to AAA. We studied structures of
      four protein-fucose complexes to examine the electrostatic potential surfaces
      around the binding site and concluded that a highly positive-charged surface was
      not a necessary condition of fucose-binding.

PMID- 15454694
TI  - Recombinant viral sialate-O-acetylesterases.
AB  - Viral O-acetylesterases were first identified in several viruses, including
      influenza C viruses and coronaviruses. These enzymes are capable of removing
      cellular receptors from the surface of target cells. Hence they are also known as
      "receptor destroying" enzymes. We have cloned and expressed several recombinant
      viral O-acetylesterases. These enzymes were secreted from Sf9 insect cells as
      chimeric proteins fused to eGFP. A purification scheme to isolate the recombinant
      O-acetylesterase of influenza C virus was developed. The recombinant enzymes
      derived from influenza C viruses specifically hydrolyze 9-O-acetylated sialic
      acids, while that of sialodacryoadenitis virus, a rat coronavirus related to
      mouse hepatitis virus, is specific for 4-O-acetylated sialic acid. The
      recombinant esterases were shown to specifically de-O-acetylate sialic acids on
      glycoconjugates. We have also expressed esterase knockout proteins of the
      influenza C virus hemagglutinin-esterase. The recombinant viral proteins can be
      used to unambiguously identify O-acetylated acids in a variety of assays.

PMID- 15454695
TI  - Apoptosis of human carcinoma cells in the presence of potential anti-cancer
      drugs: III. Treatment of Colo-205 and SKBR3 cells with: cis -platin, Tamoxifen,
      Melphalan, Betulinic acid, L-PDMP, L-PPMP, and GD3 ganglioside.
AB  - Breast cancer is the most common type of cancer, predominantly among women over
      20, whereas colo-rectal cancer occurs in both men and women over the age of 50.
      Chemotherapy of both cancers affect rapidly growing normal as well as cancer
      cells. Cancer cells are non-apoptotic. Seven anti-cancer agents (cis -platin,
      Tamoxifen, Melphalan, Betulinic acid, D-PDMP, L-PPMP, and GD3) have been tested
      with human breast (SKBR3) and colon (Colo-205) carcinoma cells for their
      apoptotic effect and found to be positive by several assay systems. Colo-205
      cells were obtained from ATCC, and the SKBR3 cells were a gift from the Cleveland
      Clinic. All of these six agents killed those two cell lines in a dose-dependent
      manner. In the early apoptotic stage (6 h), these cells showed only a flopping of
      phosphatidylserine on the outer lamella of the plasma membranes as evidenced by
      the binding of a novel fluorescent dye PSS-380. After 24 h of the treatment,
      those apoptotic cells showed damage of the plasma as well as the nuclear membrane
      as evidenced by binding of propidium iodide to the nuclear DNA. DNA laddering
      assay viewed further breakdown of DNA by 1% agarose gel electrophoresis analysis.
      It is concluded that during apoptosis the signaling by Mitochondrial Signaling
      Pathway (MSP) is stimulated by some of these agents. Caspase 3 was activated with
      the concomitant appearance of its p17 polypeptide as viewed by Westernblot
      analyses. Incorporation of radioactivity from [U-(14)C]-L-serine in total
      sphingolipid mixture was observed between 2 and 4 micromolar concentrations of
      most of the agents except ci s-platin. However, apoptosis in carcinoma cells in
      the presence of cis -platin is induced by a caspase 3 activation pathway without
      any increase in synthesis of ceramide.

PMID- 15454696
TI  - Glycosphingolipids and mitochondria: role in apoptosis and disease.
AB  - Glycosphingolipids (GSLs) comprise a class of lipids with important structural
      and signaling functions. Synthesized from ceramide in the Golgi, they are
      subsequently distributed to different compartments, most predominantly in the
      plasma membrane where they integrate signaling platforms. A recently
      characterized trafficking of ganglioside GD3 (GD3), a GSLs with two sialic-acid
      residues, to mitochondria has revealed a novel function of this lipid as a death
      effector. In addition to the interaction of GD3 with mitochondria recruiting
      these organelles to apoptotic pathways, GD3 disables survival paths dependent on
      NF-kappaB, thus favoring the balance towards cell death. The present review
      gathers the evidence documenting this emerging function of GSLs in cell death and
      their involvement in pathological states.

PMID- 15454697
TI  - Inflammatory cytokines released from the facet joint tissue in degenerative
      lumbar spinal disorders.
AB  - STUDY DESIGN: A prospective study of surgical cases of degenerative lumbar spinal
      disorders demonstrated inflammatory cytokines in the facet joint tissue.
      OBJECTIVE: To quantify various inflammatory cytokines released from the facet
      joint tissue in surgical cases of degenerative lumbar spinal disorders. SUMMARY
      OF BACKGROUND DATA: In degenerative lumbar spinal disorders, pain is often caused
      by osteoarthritis of a facet joint. There are inflammatory mediators such as
      prostaglandins and leukotrienes in facet joint tissue in lumbar spinal
      degeneration. However, no reports have studied if there are also inflammatory
      cytokines in the facet joint, which generated arthropathic changes in
      degenerative lumbar spinal disorder and if pain is caused by chemical factors
      associated with inflammation such as inflammatory cytokines. METHODS: Forty
      patients with degenerative lumbar disorders who had undergone operative treatment
      were included in this study. Fifty-five joint cartilages and 67 synovia were
      harvested from the lumbar facet joints in responsible intervertebral levels of
      patients. There were 24 male and 16 female subjects with average ages of 50 and
      67 years, respectively, in 11 cases of lumbar disc herniation and 29 cases of
      lumbar spinal canal stenosis. Using ELISA and CLEIA methods, joint cartilage and
      synovial tissues were harvested during surgery from the facet joint at the
      responsible upper levels to measure IL-1beta, TNF-alpha, and IL-6 in individual
      tissues. RESULTS: IL-1beta was detected in joint cartilage and synovium in both
      groups and its positive reaction rate was higher in LSCS than in LDH. There was
      no difference in IL-1beta concentration in cartilage tissue between the two
      groups. There was TNF-alpha in the synovium of LSCS. IL-6 was high in joint
      cartilage and synovium in both groups. The concentration was significantly higher
      in LSCS than in LDH. CONCLUSIONS: There are inflammatory cytokines in facet joint
      tissue at high levels in degenerative lumbar spinal disorders. Inflammatory
      cytokines have a higher concentration rate in lumbar spinal canal stenosis than
      in lumbar disc herniation. This finding suggests that inflammatory cytokines in
      degenerated facet joints may have some relation to the cause of pain in
      degenerative lumbar disorders.

PMID- 15454698
TI  - Biomechanical analysis of anterior poly-methyl-methacrylate reconstruction
      following total spondylectomy for metastatic disease.
AB  - STUDY DESIGN: Three reconstruction options were evaluated biomechanically
      following total spondylectomy using human cadaveric spine specimens. OBJECTIVES.:
      To evaluate and compare the stability of combined anterior and posterior fixation
      incorporating poly-methyl-methacrylate with alternative accepted reconstruction
      techniques. SUMMARY OF BACKGROUND DATA: Total spondylectomy represents the most
      radical option for decompression in metastatic spinal cord compression. Poly
      methyl-methacrylate is considered a useful adjunct in spinal column stabilization
      and arthrodesis; however, there is little published biomechanical data to support
      its use in this setting. METHODS: Ten fresh-frozen human cadaveric spines (T9-L3)
      were used. After intact analysis, a total spondylectomy was performed at T12.
      Three potential reconstruction techniques were tested for their ability to
      restore stiffness to the specimen: 1) multilevel posterior pedicle screw
      instrumentation from T10-L2; 2) anterior instrumentation (ATL Z plate II) and rib
      graft at T11-L1 with multilevel posterior pedicle screw instrumentation from T10
      L2; and 3) anterior cement (Simplex P) and pins construct (T12) with multilevel
      posterior pedicle screw instrumentation from T10-L2. Each of the three potential
      reconstruction techniques was tested on each specimen in random order using
      nondestructive testing under load control. RESULTS: Only combined stabilization
      techniques (e.g., anterior instrumentation and rib graft with multilevel
      posterior pedicle screw instrumentation and anterior cement-and-pins construct
      with multilevel posterior pedicle screw instrumentation) restored stiffness to a
      level equivalent to or higher than that of the intact spine in all loading modes
      (P < 0.05). Anterior cement-and-pins construct with multilevel posterior pedicle
      screw instrumentation provided more stability to the specimen than anterior
      instrumentation and rib graft with multilevel posterior pedicle screw
      instrumentation in compression and flexion testing (P < 0.05). Posterior
      instrumentation alone did not restore stiffness to the intact level in
      compression and flexion testing (P < 0.005). CONCLUSIONS: Combined anterior and
      posterior reconstruction using a cement construct provides equal to or more
      stability than the intact spine in all testing modes. Posterior stabilization
      alone is an inferior method of reconstruction following total spondylectomy. Poly
      methyl-methacrylate has the advantage over traditional anterior reconstruction
      techniques in that it can be inserted using a posterior approach.

PMID- 15454699
TI  - Muscle activation strategies and symmetry of spinal loading in the lumbar spine
      with scoliosis.
AB  - STUDY DESIGN: Biomechanical analysis of muscle and spinal forces in a lumbar
      spine with scoliosis. OBJECTIVES: To calculate spinal loading asymmetry and its
      dependence on muscle activation strategy. SUMMARY OF BACKGROUND DATA: It is
      commonly assumed that a spine with scoliosis experiences greater loading on the
      concave side and that this asymmetric loading causes asymmetric growth and
      progression of deformity. However, neither the magnitude of the asymmetric
      loading imposed on the spine as a function of the scoliosis curve nor the
      resulting mechanically altered vertebral growth and disc remodeling have been
      quantified. METHODS: Spinal loading was estimated in a lumbar spine model with
      increasing degrees of scoliosis. External loading was each of three pure moments
      or forces acting at T12, with magnitudes of either 50% or 75% of maximum effort.
      For each external loading, the muscle activation patterns were determined with
      each of three different muscle activation strategies in an optimization model: 1)
      minimize the sum of cubed muscle stresses; 2) minimize spinal asymmetric load
      (i.e., "follower load"); and 3) reverse the spinal load asymmetry (increased
      compression on convex side) at the level of the apex. RESULTS: The first strategy
      produced loading that tended to increase the curve magnitude, with the resultant
      force acting at up to 15 mm lateral to the intervertebral disc center. Both
      Strategies 2 and 3 had increased muscle stress averaging between 42% and 75%.
      CONCLUSIONS: We speculate that individuals with scoliosis can adopt different
      muscle activation strategies and that these strategies may determine whether or
      not the spinal loading causes scoliosis progression during growth. Muscle
      activation patterns generating spinal loading that does not promote curve
      progression during growth have greater physiologic cost.

PMID- 15454700
TI  - Patients with neck pain demonstrate reduced electromyographic activity of the
      deep cervical flexor muscles during performance of the craniocervical flexion
      test.
AB  - STUDY DESIGN: Cross-sectional study. OBJECTIVE: The present study compared
      activity of deep and superficial cervical flexor muscles and craniocervical
      flexion range of motion during a test of craniocervical flexion between 10
      patients with chronic neck pain and 10 controls. SUMMARY OF BACKGROUND DATA:
      Individuals with chronic neck pain exhibit reduced performance on a test of
      craniocervical flexion, and training of this maneuver is effective in management
      of neck complaints. Although this test is hypothesized to reflect dysfunction of
      the deep cervical flexor muscles, this has not been tested. METHODS: Deep
      cervical flexor electromyographic activity was recorded with custom electrodes
      inserted via the nose and fixed by suction to the posterior mucosa of the
      oropharynx. Surface electrodes were placed over the superficial neck muscles
      (sternocleidomastoid and anterior scalene). Root mean square electromyographic
      amplitude and craniocervical flexion range of motion was measured during five
      incremental levels of craniocervical flexion in supine. RESULTS: There was a
      strong linear relation between the electromyographic amplitude of the deep
      cervical flexor muscles and the incremental stages of the craniocervical flexion
      test for control and individuals with neck pain (P = 0.002). However, the
      amplitude of deep cervical flexor electromyographic activity was less for the
      group with neck pain than controls, and this difference was significant for the
      higher increments of the task (P < 0.05). Although not significant, there was a
      strong trend for greater sternocleidomastoid and anterior scalene
      electromyographic activity for the group with neck pain. CONCLUSIONS: These data
      confirm that reduced performance of the craniocervical flexion test is associated
      with dysfunction of the deep cervical flexor muscles and support the validity of
      this test for patients with neck pain.

PMID- 15454701
TI  - Efficacy of infliximab for disc herniation-induced sciatica: one-year follow-up.
AB  - STUDY DESIGN: An open-label trial. OBJECTIVES: To test the long-term efficacy of
      infliximab, a monoclonal antibody against tumor necrosis factor-alpha (TNF
      alpha), in disc herniation-induced sciatica. SUMMARY OF BACKGROUND DATA: Our
      recent trial indicated that a single infusion of 3 mg/weight-kg of infliximab
      produced a rapid curative effect in disc herniation-induced sciatica. Here, we
      describe the 1-year effect of a 3 mg/kg of infliximab in these 10 patients and
      our experience with a lower dose of 1 mg/kg of infliximab for the same indication
      in 2 additional patients. METHODS: Patients with severe sciatica were treated
      with a single infusion of infliximab, 3 mg/weight-kg in 10 patients and 1 mg/kg
      in 2 patients, intravenously over 2 hours. The outcomes (leg and back pain on a
      100-mm visual scale, Oswestry disability, clinical signs) were assessed at 1
      week, 2 weeks, 1 month, 3 months, 6 months, and 1 year after the infusion. The
      outcomes with 3 mg/kg of infliximab were compared to 62 patients who received
      periradicular saline for sciatica in a previous trial. The resorption rate of
      disc herniations from baseline to 1 year was compared between infliximab and
      control groups. RESULTS: The response to 1 mg/kg of infliximab for leg pain was
      good only in 1 of the 2 patients treated, whereas the response to 3 mg/kg of
      infliximab for leg pain was sustained in most patients over the 1-year follow-up.
      The 1-year response significantly favored 3 mg/kg of infliximab over
      periradicular saline in leg pain (P = 0.005) and disability (P = 0.003).
      Neurologic abnormalities normalized more comprehensively in the infliximab group
      (P = 0.001). Reduction in disc herniation volume did not differ between the
      infliximab-treated patients and controls. CONCLUSIONS: The results showed that
      the beneficial effect of a single infusion of 3 mg/kg of infliximab for
      herniation-induced sciatica is sustained in most patients over a 1-year follow-up
      period. Furthermore, infliximab does not seem to interfere with the spontaneous
      resorption of disc herniations.

PMID- 15454702
TI  - Primary and secondary osteoporosis' incidence of subsequent vertebral compression
      fractures after kyphoplasty.
AB  - STUDY DESIGN: Retrospective review of prospective database. OBJECTIVES: Define
      the incidence of adjacent and remote fractures after kyphoplasty vertebral
      augmentation, and identify vulnerable subpopulations at increased risks. SUMMARY
      OF BACKGROUND DATA: Painful osteoporotic compression fractures can be effectively
      treated with methyl methacrylate vertebral augmentation, but the effect of
      intervention on the generation of future remote and adjacent fractures has not
      been identified. No paper has analyzed the association of long-term steroid use
      to subsequent compression fractures. METHODS: A total of 175 patients were
      treated for compression fractures, from October 1999 to November 2001, 60
      patients were excluded due to insufficient follow-up (less than 3 months) or
      malignancy related fracture. The remaining 115 patients' charts and radiographs
      were then individually analyzed. New fractures were identified based on changes
      from baseline imaging studies (). Demographic information, vertebral levels
      treated, adjacent fractures, and remote fractures underwent statistical analyzed
      (P < 0.05). RESULTS: A total of 225 vertebral bodies were treated in 115 patients
      using the kyphoplasty technique; of those, 26 patients developed 34 subsequent
      compression fractures. The mean follow-up was 11 months (range, 3-33 months). The
      incidence of subsequent fracture per procedure per kyphoplasty was 15.1% (34 of
      225), overall incidence per patient was 22.6% (26 of 115). There were 80 patients
      with primary osteoporosis and 35 patients with secondary steroid-induced
      osteoporosis. These populations were similar in terms of demographics, single or
      multiple sites, along with two or three adjacent levels treated. Seventeen of the
      26 (65%) patients with subsequent fracture had secondary steroid-induced
      osteoporosis, while only 9 of the 26 (35%) patients had primary osteoporosis.
      Therefore, the incidence of post-kyphoplasty VCF in the primary osteoporotic
      patient was 11.25% (9 of 80) and the incidence in the steroid-induced
      osteoporotic patient was 48.6% (17 of 35). This increased fracture rate in the
      steroid-dependent patients was significant (P < 0.0001), along with adjacent
      fractures (12 of 19 on steroids, P = 0.0009), and remote fractures (7 of 9 on
      steroids, P = 0.027). CONCLUSIONS: Steroid-induced compression fractures appear
      to have an increased incidence of subsequent fractures after the kyphoplasty
      procedure. The kyphoplasty protocol with concurrent medical osteoporotic regimen
      does not appear to increase, and may serve to reduce, the incidence of remote and
      adjacent fractures for primary osteoporotic fractures.

PMID- 15454703
TI  - Prolotherapy injections for chronic low back pain: a systematic review.
AB  - STUDY DESIGN: A systematic review of randomized and quasi-randomized controlled
      trials. OBJECTIVES: To determine the efficacy of prolotherapy injections in
      adults with chronic low back pain. SUMMARY OF BACKGROUND DATA: Prolotherapy is an
      injection-based treatment for chronic low back pain. Proponents of prolotherapy
      suggest that some back pain stems from weakened or damaged ligaments. Repeatedly
      injecting them with irritant solutions is thought to strengthen the ligaments and
      reduce pain and disability. Prolotherapy protocols usually include co
      interventions to enhance the effectiveness of the injections. METHODS: The
      authors searched MEDLINE, EMBASE, CINAHL, and Science Citation Index up to
      January 2004, and the Cochrane Controlled Trials Register 2004, issue 1, and
      consulted content experts. Both randomized and quasi-randomized controlled trials
      comparing prolotherapy injections to control injections, either alone or in
      combination with other treatments, were included. Studies had to include measures
      of pain and disability before and after the intervention. Two reviewers
      independently selected the trials and assessed them for methodologic quality.
      Treatment and control group protocols varied from study to study, making meta
      analysis impossible. RESULTS: Four studies, all of high quality and with a total
      of 344 participants, were included. All trials measured pain and disability
      levels at 6 months, three measured the proportion of participants reporting a
      greater than 50% reduction in pain or disability scores from baseline to 6
      months. Two studies showed significant differences between the treatment and
      control groups for those reporting more than 50% reduction in pain or disability.
      Their results could not be pooled. In one, co-interventions confounded
      interpretation of results; in the other, there was no significant difference in
      mean pain and disability scores between the groups. In the third study, there was
      little or no difference between groups in the number of individuals who reported
      more than 50% improvement in pain and disability. The fourth study reporting only
      mean pain and disability scores showed no differences between groups.
      CONCLUSIONS: There is conflicting evidence regarding the efficacy of prolotherapy
      injections in reducing pain and disability in patients with chronic low back
      pain. Conclusions are confounded by clinical heterogeneity among studies and by
      the presence of co-interventions. There was no evidence that prolotherapy
      injections alone were more effective than control injections alone. However, in
      the presence of co-interventions, prolotherapy injections were more effective
      than control injections, more so when both injections and co-interventions were
      controlled concurrently.

PMID- 15454704
TI  - Subgroups of positive discs on discography.
AB  - STUDY DESIGN: Retrospective study of pressure-controlled discography (PCD) in
      patients with chronic low back pain (CLBP). OBJECTIVES: Define the distribution
      of disc pain thresholds and determine, using an analytical model, if a false
      positive subgroup could be identified. SUMMARY OF BACKGROUND DATA: The
      characteristics of the distribution of disc pain thresholds may allow
      identification of subgroups within a population. METHODS: Disc pain thresholds
      were determined using PCD in patients with CLBP referred for discography. An
      analytical model and previously published data from an asymptomatic group were
      used to determine the distribution of false-positive discs. RESULTS: A total of
      838 discs from 253 patients were studied. Regression analysis demonstrated no
      significant association between levels from patients with CLBP with more than one
      positive disc. The distribution of discography pain thresholds from the patients
      with CLBP revealed two distinct groups: contact-sensitive (CS) and pressure
      sensitive (PS). Discs in the CS group have a pain threshold of 0 psi, indicating
      that contact between the contrast and the disc provokes pain. Discs in the PS
      group have a pain threshold of > 0 psi, demonstrating that internal pressure must
      be generated to provoke pain. PS discs consist of moderately and minimally
      sensitive subgroups, with overlapping distributions. The minimally sensitive
      subgroup corresponds to false-positive discs. At 50 psi, the probability of a
      false-positive disc is 100%, at 25 psi 50%, at 19 psi 25%, and at 14 psi 10%.
      CONCLUSIONS: Discography should be performed under pressure control, as doing so
      allows the pain threshold of discs to be quantified, and the probability that a
      disc is false-positive estimated.

PMID- 15454705
TI  - Value of magnetic resonance imaging and discography in determining the level of
      cervical discectomy and fusion.
AB  - STUDY DESIGN: The correlation between magnetic resonance imaging and discography
      of the cervical spine in degenerative disc disease was studied. In addition, the
      results of cervical discectomy and fusion were evaluated. OBJECTIVES: To compare
      the value of cervical magnetic resonance imaging versus discography in selecting
      the level for discectomy and fusion and to evaluate the surgical outcome. SUMMARY
      OF BACKGROUND DATA: The value of magnetic resonance imaging and discography in
      patients with cervical discogenic pain is less clear. Also, the status of a
      hypointense signal (dark) cervical disc and/or a small herniated disc on magnetic
      resonance imaging has not been determined. METHODS: The magnetic resonance
      imaging studies and discography followed by computed tomography in 55 patients
      with cervical discogenic pain were evaluated. Surgical planning was based on the
      complete information of clinical symptoms, magnetic resonance imaging, and
      discography as well as computed tomography discography. Anterior cervical
      discectomy and keystone fusion was performed. Postoperative pain relief was
      assessed by the patients, and the follow-up radiographs were viewed by an
      independent reviewer. The overall surgical outcome was evaluated using Odom's
      criteria. RESULTS: There were 161 disc levels that successfully underwent
      cervical discography with 79 positive levels. A positive discography result was
      found in 63% of dark (hypointense signal) discs and 45% of speckled discs. Fifty
      nine percent of small herniated discs and 59% of torn discs had a positive
      discography, respectively. There were 100 abnormal cervical discs on magnetic
      resonance imaging. Magnetic resonance imaging had a false-positive rate of 51%
      and a false-negative rate of 27%. Successful cervical fusion was achieved in 95%
      of patients, and the overall satisfactory result was 76%. CONCLUSIONS: Magnetic
      resonance imaging can identify most of the painful discs but still has relatively
      high false-negative and false-positive rates. There is a high chance that
      hypointense signal and small herniated discs are the pain generators, but they
      are not always symptomatic. Discography can save the levels from being
      unnecessarily fused. The combination of clinical symptoms, magnetic resonance
      imaging, and discography provides the most information for decision making and
      can improve the management of cervical discogenic pain.

PMID- 15454707
TI  - MR aortography and serum cholesterol levels in patients with long-term
      nonspecific lower back pain.
AB  - STUDY DESIGN: A cross-sectional analysis of the feeding arteries of the lumbar
      spine and cholesterol levels on patients with long-term nonspecific lower back
      pain. OBJECTIVES: To evaluate whether occlusion of lumbar and middle sacral
      arteries or serum cholesterol levels are associated with lower back pain and/or
      with disc degeneration. SUMMARY OF BACKGROUND DATA: Atherosclerosis in the wall
      of the abdominal aorta usually develops at the ostia of branching arteries and
      the bifurcation, and may obliterate orifices of lumbar and middle sacral
      arteries. Obstruction of these arteries causes ischemia in the lumbar spine and
      may result in back symptoms and disc degeneration. METHODS: MR aortography and
      cholesterol blood tests were performed on 51 patients with long-term lower back
      pain without specific findings (i.e., spinal or nerve root compression) in
      regular lumbar MR images. The patients ranged from 35 to 70 years of age (mean
      age, 56 years). Serum cholesterol and low-density lipoprotein (LDL) cholesterol
      levels were measured. To assess symptoms and disability NASS low back Outcome
      Instrument was used. RESULTS: Twenty-nine (78%) of 37 men and 11 (77%) of 14
      women showed occluded lumbar and/or middle sacral arteries. The prevalence of
      occluded arteries was 2.5 times more than in subjects of corresponding age group
      in a Finnish necropsy material. Twenty-three (62%) men and seven (50%) women had
      significant disc degeneration. Disc degeneration was associated with occluded
      lumbar/middle sacral arteries (P = 0.035). Patients with occluded arteries or
      significant disc degeneration did not complain more severe symptoms than those
      without, whereas patients with above normal serum LDL cholesterol scored higher
      in neurogenic symptoms (P = 0.031) and complained more often severe pain (P =
      0.049) than those with normal LDL cholesterol. CONCLUSIONS: The study indicates
      that lumbar and middle sacral arteries are often occluded in patients with
      nonspecific long-term lower back pain. Occlusion of these arteries may also be
      associated with disc degeneration.

PMID- 15454708
TI  - Transcranial electrical stimulation as predictor of elicitation of intraoperative
      muscle-evoked potentials.
AB  - STUDY DESIGN: Preoperative electrophysiological and neurologic findings from
      patients with cervical myelopathy were evaluated statistically to determine their
      predictive value relative to the success of eliciting intraoperative motor-evoked
      potentials. OBJECTIVES: To determine which preoperative variables accurately
      predicted the success of eliciting an intraoperative muscle-evoked potential.
      SUMMARY OF BACKGROUND DATA: Motor-evoked potential recorded from the muscles
      after transcranial electrical stimulation is one of the most widely used methods
      for intraoperative spinal cord monitoring. However, motor-evoked potentials
      recorded from lower limb muscles are not detectable in patients with severe
      cervical myelopathy. Therefore, it is helpful to know the probability of the
      intraoperative transcranial electrical stimulation-motor evoked potential
      elicitation before the operation. METHODS: There were 38 patients with cervical
      myelopathy. Before the operation, motor-evoked potentials following transcranial
      magnetic stimulation were recorded from the flexor hallucis brevis, and central
      motor conduction times were measured. Neurologic function was evaluated using the
      Japanese Orthopedic Association score. During the operation, transcranial
      electrical stimulation-motor evoked potential from the flexor hallucis brevis was
      recorded. The Japanese Orthopedic Association score, threshold intensity of
      magnetic stimulation, and central motor conduction times were statistically
      evaluated for their potential of being predictors. RESULTS: The intraoperative
      transcranial electrical stimulation-motor evoked potential was detectable in all
      cases in which the preoperative transcranial magnetic stimulation-motor evoked
      potential was elicited by a lower intensity than 50% of the maximum output of the
      stimulator. Therefore, simultaneous use of other methods of monitoring should be
      considered in such cases that need higher output. However, the Japanese
      Orthopedic Association score or central motor conduction times were not useful
      criteria. CONCLUSIONS.: The threshold intensity of the preoperative transcranial
      magnetic stimulation-motor evoked potential was helpful in predicting elicitation
      of the intraoperative transcranial electrical stimulation-motor evoked potential.

PMID- 15454709
TI  - Relevance of aerobic capacity measurements in the treatment of chronic work
      related spinal disorders.
AB  - STUDY DESIGN: Prospective cohort study of rehab program completers, comparing
      aerobic capacity data of chronic lumbar spinal disorder patients (CLSD) to that
      of chronic cervical spinal disorder (CCSD), collected from a tertiary care
      facility. OBJECTIVE: We evaluated whether CLSD is associated with different pre-
      and postrehabilitation aerobic capacity deficits than CCSD, and whether such
      deficits affect functional restoration outcomes. SUMMARY OF BACKGROUND DATA:
      Chronic spinal disorder patients are thought to lose aerobic fitness as a
      component of the deconditioning syndrome. Patients with CLSD often restrict
      aerobic activities because of back or leg pain, while CCSD patients generally do
      so to a lesser degree. We hypothesized that those with CLSD would have greater
      deficits in tests of aerobic fitness than patients with CCSD both before and
      after treatment. METHODS: From a consecutive cohort of 683 patients with work
      related spinal disorders, two groups were identified: patients with CLSD (n =
      504; age 40.1 years; 68% male); and patients with CCSD (n = 179; 41.3 years; 43%
      male). All patients completed an intensive, medically supervised functional
      restoration program. Before and after the program, patients completed a
      submaximal bicycle ergometer aerobic capacity test and a psychosocial test
      battery. A structured clinical interview to determine socioeconomic outcomes was
      conducted 1 year after the program completion. RESULTS: Of CLSD patients 33% and
      11% of CCSD patients (P < 0.001) either failed to produce any torque or could not
      complete at least 2 stages on the bicycle on preprogram tests (invalid tests).
      However, all patients had valid bicycle tests at program completion. Nearly two
      thirds of the subjects with initially invalid tests in the lumbar group failed to
      develop any torque, while only one-third of subjects with invalid tests of the
      cervical group had a similar result. Thus, CLSD is associated with greater
      prerehabiliation aerobic fitness deficits than CCSD. Overall, there was no
      significant change in pre to postrehab aerobic capacities for the initially valid
      test subjects. The initially invalid test subjects achieved similar
      postrehabilitation scores compared to the valid test subjects, although CLSD
      patients with initially valid tests performed slightly better at the posttest.
      Socioeconomic outcomes were the same one year after the program for valid and
      invalid test subjects. CLSD patients had higher preprogram self reports of
      disability. The subgroup of the initially invalid test subjects that produced no
      torque whatsoever (19.3% of CLSD and 3.9% of CCSD) did not differ from the
      subgroup that failed to complete 2 stages in the pretest of aerobic performance
      on depression. They had higher pretest self-reported disability. CONCLUSIONS:
      Although mean aerobic fitness levels for all patients improved during
      rehabilitation, the improvement is almost entirely accounted for by initially
      invalid tests becoming valid. Aerobic capacity testing measured with submaximal
      bicycle ergometry may frequently be invalid when fear-avoidance limits effort,
      particularly in CLSD. Psychosocial fear-avoidance, as it applies to bicycle
      ergometry, can be overcome in virtually all patients motivated to complete a
      tertiary rehabilitation program. As such, prerehabilitation aerobic capacity
      testing is a poor differentiator of postrehabilitation outcomes.

PMID- 15454711
TI  - Correlation between pre-employment screening X-ray finding of spondylolysis and
      sickness absenteeism due to low back pain among policemen of the Israeli police
      force.
AB  - STUDY DESIGN: A historical prospective case/control study of the significance and
      correlation between pre-employment findings of L5-S1 spondylolysis and sickness
      absenteeism due to low back pain among police officers. OBJECTIVES: Examining the
      importance of pre-employment lumbar spine radiographs as a prediction of work
      absenteeism. SUMMARY OF BACKGROUND DATA: Spondylolysis is a defect in the pars
      interarticularis. Its etiology remains controversial, it is a common condition
      among young athletes, and it carries genetic predisposition. Although described
      mostly as an incidental radiographic finding in the adult population,
      spondylolysis is implicated as a contributing factor to low back pain, although
      the cause-and-effect relation is not clear. METHODS: One hundred and sixty-nine
      police officers with L5-S1 spondylolysis were identified out of 3988 examined.
      Incidence density of sickness absenteeism due to low back pain was calculated for
      the patients and the controls. The Cox's proportional hazard model was used for
      comparison between the two groups, controlling for possible confounding
      variables. RESULTS: Similar incidence of sickness absenteeism due to low back
      pain was found among the patients and controls. The total duration of sickness
      absenteeism, however, was 2.7 times higher in the spondylolysis group than the
      controls. Prevalence of spondylolysis is origin specific, denoting genetic
      predisposition to this condition. Total sickness absenteeism not related to low
      back pain was not significantly different between the two study groups.
      CONCLUSIONS: There is low predictive value of pre-employment lumbar spine
      radiograph as a screening tool predicting sickness absenteeism due to low back
      pain. Spondylolysis, however, may increase the duration of sickness absenteeism
      in patients with low back pain.

PMID- 15454712
TI  - Survey of general practitioner, family physician, and chiropractor's beliefs
      regarding the management of acute whiplash patients.
AB  - STUDY DESIGN: Questionnaire Survey. OBJECTIVE: The purpose of this study was to
      survey the whiplash management beliefs for practicing general practitioners,
      family physicians, and chiropractors. SUMMARY OF BACKGROUND DATA: Many treatments
      are prescribed by general practitioners, family physicians, and chiropractors for
      acute whiplash, but to date no survey of management beliefs for acute whiplash
      has been reported. METHODS: A total of 483 physicians and 123 chiropractors in
      the urban setting of Edmonton, Alberta, Canada were asked to participate by
      completing a questionnaire with 24 items designed to assess management beliefs
      regarding acute whiplash. RESULTS: A total of 362 physicians (75%) and 88
      chiropractors (72%) completed the survey. Only 1% of physicians and none of the
      chiropractors believed that whiplash patients should be prescribed bed rest until
      almost all their pain goes away. As well, only 1% of physicians and none of the
      chiropractors believed that patients with acute whiplash should not return to
      work until almost all their pain goes away. More than 89% of physicians and 76%
      of chiropractors believed that encouragement of maintaining normal activities,
      even if they hurt, is important in the recovery from whiplash. Also, 91% of
      physicians and 84% of chiropractors agreed that exercise therapy was effective in
      acute whiplash patients. Physicians are more likely to have negative feelings
      about treating patients who have whiplash, were more likely to believe there was
      nothing physically wrong with many patients with chronic whiplash, and agree that
      nonsteroidal anti-inflammatory drugs and muscle relaxants are effective in acute
      whiplash. Chiropractors are more likely to agree that traction, transcutaneous
      electrical nerve stimulation, manipulation, massage, and acupuncture are
      effective in acute whiplash. CONCLUSIONS: Physicians and chiropractors generally
      hold beliefs that are consistent with the current evidence regarding the most
      helpful approaches to acute whiplash, although chiropractors were more likely to
      be supportive of passive therapy methods.

PMID- 15454713
TI  - Interrelationships between pain, disability, general health, and quality of life
      and associations with work-related and individual factors: a study among workers
      on sickness absence for 2 to 6 weeks for musculoskeletal complaints.
AB  - STUDY DESIGN: A cross-sectional study. OBJECTIVES: To measure interrelationships
      among pain, functional disability, general health, and overall quality of life
      for workers on sickness absence for 2 to 6 weeks due to musculoskeletal
      complaints, and to assess the impact of work-related and individual
      characteristics on these different health dimensions. The results of this study
      will contribute to a better understanding of the relationship between health and
      functional disability. SUMMARY OF BACKGROUND DATA: When choosing a patient-based
      outcome measure, different health dimensions must be considered. For
      musculoskeletal complaints, four health dimensions are important: pain,
      disability, general health, and overall quality of life. Improvement at one
      dimension does not necessarily correlate with better health on another dimension.
      Moreover, correlations between different dimensions may be influenced by
      individual and environmental factors. However, it is not known whether these
      factors influence different health dimensions differently. METHODS: A total of
      218 workers on sickness absence for 2 to 6 weeks due to musculoskeletal
      complaints completed a questionnaire on four different health dimensions and work
      related and environmental factors. RESULTS: Moderate correlations (r < 0.50)
      among measures of pain, disability, general health, and quality of life were
      found. These health dimensions were not influenced by work-related physical and
      psychosocial workload, suggesting no impact of recall bias in studies for work
      related musculoskeletal complaints. Self-perceived ability to return to work
      within 6 weeks explained 21% to 26% of the outcomes on pain and disability and
      contributed less to the generic measures of health. CONCLUSION: Within a
      population of workers on sickness absence for 2 to 6 weeks, specific dimensions
      of pain and disability seem to be more appropriate measures of health than
      generic instruments of general health and quality of life.

PMID- 15454714
TI  - Are children's backpack weight limits enough? A critical review of the relevant
      literature.
AB  - STUDY DESIGN: Literature review. OBJECTIVE: To examine the epidemiologic,
      physiologic, and biomechanical literature that has contributed to the suggested
      weight limit of 10 to 15% body weight for children's backpacks. SUMMARY OF
      BACKGROUND DATA: The majority of children use a backpack to transport their
      belongings to and from school on a daily basis; however, controversy exists over
      the safety of backpack use and backpack loads. METHODS: A thorough review of the
      literature was completed to examine the appropriateness of the suggested weight
      limits and to determine future areas of research needed to increase the safety of
      children's backpacks. RESULTS: Epidemiologic, physiologic, and biomechanical data
      support the suggested weight limit of 10% to 15% body weight. CONCLUSIONS.: Based
      on the current literature, the value of 10% to 15% body weight is a justified
      weight limit; however, further research is required to determine the association
      between backpack use and injury and how the factors of load, backpack design, and
      personal characteristics, such as physical fitness, interact and influence the
      adaptations required when carrying a backpack.

PMID- 15454715
TI  - Results in the operative treatment of elderly patients with spinal meningiomas.
AB  - STUDY DESIGN: Thirty consecutive patients over 70 years of age who were operated
      on for spinal meningiomas are presented to assess surgical criteria and
      postoperative outcome. OBJECTIVES: To assess the outcome of surgically treated
      spinal meningiomas in patients in their eighth or ninth decade of life and to
      analyze the possible role of some prognostic factors. SUMMARY OF BACKGROUND DATA:
      The ageing of the population in the industrial nations has led to increased
      findings of benign spinal tumors, namely meningiomas, in the elderly. These slow
      growing tumors may prevent these patients from leading an autonomous life. Little
      is known about the outcome of spinal meningioma surgery in patients of 70 years
      or older because the number of these patients, although increasing, is still
      small. METHODS: Thirty consecutive patients over 70 years of age (mean age, 77.1
      years) were operated on for spinal meningiomas between 1986 and 2001. The
      preoperative neurologic status of the patients was graded with the Solero score,
      and the general health conditions were staged according to the American Society
      of Anesthesiology classification. Total tumor removal was achieved in 27
      patients. The follow-up period ranged from 17 to 173 months (mean, 62.7 months).
      RESULTS: There was no operative mortality, and morbidity was not significant.
      Although not significant, neurologic outcome was better in patients with a low
      preoperative Solero score than those with a high one (P = 0.06). Clinical outcome
      was not influenced by the duration of symptoms before surgery or preoperative
      American Society of Anesthesiology classification. No recurrence was observed
      during the follow-up period. CONCLUSIONS: Neurologic outcome following surgery
      was favorable in the vast majority of patients, with no mortality or significant
      morbidity. Surgery is the only treatment in elderly patients with symptomatic
      spinal meningiomas, even those with a poor preoperative neurologic condition,
      whenever there is an acceptable risk from an anesthesiological point of view.

PMID- 15454717
TI  - Re: Yelland M, Glasziou P, Bogduk N, et al. Prolotherapy injections, saline
      injections and exercises for chronic low-back pain: a randomized trial. Spine
      2004;29:9-16.

PMID- 15454718
TI  - Re: Ruf M, Melcher R, Harms J. Transoral reduction and osteosynthesis C1 as a
      function-preserving option in the treatment of unstable Jefferson fractures.
      Spine 2004;29:823-7.

PMID- 15454720
TI  - Re: Maheshwari PR, Naga AM, Prasad SS, et al. Avascular necrosis of spine: a rare
      appearance. Spine 2004;29:E119-22.

PMID- 15454721
TI  - Posterior augmentation of an anterior lumbar interbody fusion: minimally invasive
      fixation versus pedicle screws in vitro.
AB  - STUDY DESIGN: An in vitro biomechanical comparison of four posterior fixation
      techniques in the setting of an anterior lumbar interbody fusion (ALIF).
      OBJECTIVE: To compare the initial stability, in terms of range of motion and
      neutral zone, provided by pedicle screws, facet screws, translaminar facet
      screws, and H-graft plus interspinous cables in the presence of an anteriorly
      placed femoral ring allograft. SUMMARY OF BACKGROUND DATA: Pedicular fixation has
      been used to increase ALIF fusion rates but has also been linked with increased
      morbidity. Alternative posterior fixation options are available, but
      comprehensive biomechanical comparisons of these techniques do not exist.
      METHODS.: Twelve cadaveric lumbar motion segments were loaded to 5 Nm in
      unconstrained flexion-extension, lateral bending, and axial torsion. Specimens
      were tested intact, after ALIF, and after applying pedicle screws, translaminar
      screws, facet screws, and H-graft plus cables. The resulting neutral zones and
      ranges of motion were measured. RESULTS: The mean (+/-SEM) range of motion for
      each construct in flexion-extension was as follows: intact: 6.39 degrees (+/-0.47
      degrees); ALIF alone: 3.31 degrees (+/-0.22 degrees); (ALIF+) pedicle screws: 0.6
      degrees (+/-0.06 degrees); facet screws: 0.75 degrees (+/-0.12 degrees);
      translaminar screws: 0.61 degrees (+/-0.09 degrees); and H-graft: 1.74 degrees
      (+/-0.26 degrees). Pedicle, translaminar facet, and facet screws significantly
      decreased range of motion and neutral zone compared to ALIF alone in flexion
      extension, lateral bending, and axial torsion (all at P < 0.04, except
      translaminar screws in torsion neutral zone where P = 0.09). H-graft
      decreasedflexion-extension range of motion and neutral zone only (P < 0.01) and
      resulted in a significantly greater neutral zone than pedicle and facet screws in
      torsion and lateral bending neutral zones (P < 0.03). CONCLUSIONS: In the ALIF
      setting, facet screw and translaminar screw techniques, which may be associated
      with less morbidity than pedicle screws clinically, provided initial posterior
      stabilization similar to pedicular fixation in this in vitro study.

PMID- 15454722
TI  - Reliability of spinal palpation for diagnosis of back and neck pain: a systematic
      review of the literature.
AB  - STUDY DESIGN: A systematic review. OBJECTIVES: To determine the quality of the
      research and assess the interexaminer and intraexaminer reliability of spinal
      palpatory diagnostic procedures. SUMMARY OF BACKGROUND DATA: Conflicting data
      have been reported over the past 35 years regarding the reliability of spinal
      palpatory tests. METHODS: The authors used 13 electronic databases and manually
      searched the literature from January 1, 1966 to October 1, 2001. Forty-nine (6%)
      of 797 primary research articles met the inclusion criteria. Two blinded,
      independent reviewers scored each article. Consensus or a content expert
      reconciled discrepancies. RESULTS: The quality scores ranged from 25 to 79/100.
      Subject description, study design, and presentation of results were the weakest
      areas. The 12 highest quality articles found pain provocation, motion, and
      landmark location tests to have acceptable reliability (K = 0.40 or greater), but
      they were not always reproducible by other examiners under similar conditions. In
      those that used kappa statistics, a higher percentage of the pain provocation
      studies (64%) demonstrated acceptable reliability, followed by motion studies
      (58%), landmark (33%), and soft tissue studies (0%). Regional range of motion is
      more reliable than segmental range of motion, and intraexaminer reliability is
      better than interexaminer reliability. Overall, examiners' discipline, experience
      level, consensus on procedure used, training just before the study, or use of
      symptomatic subjects do not improve reliability. CONCLUSION: The quality of the
      research on interreliability and intrareliability of spinal palpatory diagnostic
      procedures needs to be improved. Pain provocation tests are most reliable. Soft
      tissue paraspinal palpatory diagnostic tests are not reliable.

PMID- 15454723
TI  - Detection of a dural defect by cinematic magnetic resonance imaging and its
      selective closure as a treatment for a spinal extradural arachnoid cyst.
AB  - STUDY DESIGN: We document a giant spinal extradural arachnoid cyst treated by
      selective closure of the dural defect. It was diagnosed using cinematic magnetic
      resonance imaging (cine-MRI). OBJECTIVE: To demonstrate the effectiveness of
      selective closure of the dural defect as a treatment for a spinal extradural
      arachnoid cyst. SUMMARY OF BACKGROUND DATA: The standard treatment for a spinal
      extradural arachnoid cyst is total resection of the cyst wall, if possible, and
      the closure of the communication site, if any, between the cyst and the
      subarachnoid space, after an extensive laminectomy. To our knowledge, selective
      closure of the dural defect through minimal laminotomy with little cyst resection
      has not been reported. METHODS: A 29-year-old woman presented with right leg
      muscle weakness and was diagnosed with an extradural arachnoid cyst ranging from
      spinal regions T11 to L3 using MRI. Myelography demonstrated that the cyst
      communicated with the subarachnoid space. Cine-MRI showed a pulsating flow
      voiding on the left side of level L1, suggesting the location of the
      communication site. Fenestration of the T12-L1 region was performed, preserving
      the spinous processes and the facet joints. A small dural rent was found on the
      left side of level L1. This was closed using small clips. RESULTS: MRI 12 days
      later demonstrated that the cyst had shrunk dramatically. It had disappeared
      completely by 4 months. The patient's muscle weakness improved gradually, and she
      was almost complaint-free 6 months after the operation. CONCLUSIONS: Selective
      closure of the dural defect based on cine-MRI will be useful for treating
      extradural arachnoid cysts.

PMID- 15454724
TI  - Prolonged retraction on the normal common carotid artery induced lethal stroke
      after cervical spine surgery.
AB  - STUDY DESIGN: Case report. OBJECTIVE: To report a previously undescribed
      complication of prolonged retraction on the normal common carotid artery after
      anterior cervical spine surgery. SUMMARY OF BACKGROUND DATA: Previous study
      showed that prolonged retraction could decrease the blood flow of the common
      carotid artery during anterior cervical spine surgery. A case report revealed
      that prolonged retraction could induce the formation of thrombosis in the
      atherosclerotic common carotid artery. METHODS: Notes review. Computed tomography
      of the brain was performed on the first and the fourth postoperative day. Carotid
      Doppler ultrasound and transcranial Doppler ultrasound were performed to evaluate
      the left common carotid artery and the left intracranial cerebral arteries.
      RESULTS: After lengthy anterior cervical spinal surgery, the patient did not
      regain his consciousness during the stay in the postoperative care unit. Large
      infarction of left cerebral hemisphere was revealed by computed tomography. The
      patient died on the seventh postoperative day of perioperative lethal stroke.
      CONCLUSION: We suggest that prolonged retraction, even on the normal common
      carotid artery, could induce lethal stroke after anterior cervical spine surgery.
      We recommend that retractor should be placed carefully and cerebral perfusion
      should be maintained adequately.

PMID- 15454725
TI  - The unique complications of coccidioidomycosis of the spine: a detailed time line
      of disease progression and suppression.
AB  - STUDY DESIGN: A case report is presented. OBJECTIVE: We report a detailed time
      line of disease progression and suppression in a patient with disseminated
      Coccidioidomycosis of the spine. The importance of consistent and thorough
      treatment to prevent disease recurrence is underscored. SUMMARY OF BACKGROUND
      DATA: Coccidioides immitis is a dimorphic fungus that lives as a saprophyte in
      arid, alkaline soils and as a parasite in the tissues of its host. Endemic to the
      arid soil of the American Southwest and Central and South America, its disease
      prevalence is increasing. There are 100,000 new infections diagnosed each year,
      of which 34% are symptomatic. Of the symptomatic individuals 5-10% will develop a
      serious pulmonary infection and of those that have a serious infection less than
      1% will develop chronic pulmonary disease and/or extrapulmonary dissemination.
      METHODS: A 36-year-old black woman with a 3-year history of recent migration to
      the desert Southwest and a family history of sarcoidosis presented to her primary
      care physician with shortness of breath and a cough of 2 months' duration. An
      anterior-posterior radiograph revealed bilateral hilar lymphadenopathy and
      sarcoidosis was diagnosed. The patient was placed on oral prednisone and
      progressively worsened. She was referred to the Orthopedic Clinic with a
      complaint of severe back pain. RESULTS: Plain radiographs of the lumbar spine
      revealed lytic erosion of the sacral promontory. Computed tomography confirmed
      the sacral lesion in addition to revealing involvement of the fifth lumbar
      vertebral body. Over the ensuing years the patient underwent a course of
      operative and chemotherapeutic therapies. She endured numerous complications of
      the disease, one of which is being reported for the first time. Control of her
      disease has been accomplished through radical surgical debridement, spinal
      stabilization with concomitant local and systemic chemotherapy. CONCLUSIONS: The
      prevalence and distribution of Coccidioidomycosis is increasing as is the
      likelihood of seeing its often unique and bizarre clinical manifestations and
      complications. If included in the differential diagnosis, the disease can be
      recognized earlier and the likelihood of numerous complications can be avoided.
      Once bony involvement is diagnosed a regimen of aggressive surgical debridement
      as well as consistent chemotherapy must be employed if remission and/or
      eradication of the illness are sought.

PMID- 15454728
TI  - Regulation of CYP3A4 by the bile acid receptor FXR: evidence for functional
      binding sites in the CYP3A4 gene.
AB  - CYP3A4, the most abundant cytochrome P450 in human liver, is responsible for the
      metabolism of numerous xenobiotics and endobiotics. CYP3A4 expression is highly
      variable and is induced by numerous compounds of exogenous and endogenous origin,
      including elevated concentrations of secondary bile acids via the pregnane X
      receptor (PXR). We show that physiological concentrations of the primary bile
      acid chenodeoxycholic acid regulate the expression of CYP3A4 via the bile acid
      receptor FXR. Experiments performed in vitro in different cell culture systems,
      gel-mobility shift assays and experiments performed in vivo in transgenic mice
      lacking FXR or PXR and treated with the synthetic FXR agonist GW4064 were
      undertaken to study the implication of FXR in the regulation of CYP3A. Our data
      provide evidence for the presence of two functional FXR recognition sites located
      in a 345-bp element within the 5'-flanking region of CYP3A4. Mutational analysis
      of these sites and experiments in transgenic mice lacking FXR or PXR support the
      relevance of FXR activation for CYP3A regulation. Thus, whereas elevated
      concentrations of precursors of bile acids and secondary bile acids induce CYP3A
      via PXR, primary bile acids can modulate the expression of CYP3A via FXR. These
      findings may explain elevated CYP3A expression in cholestasis and part of the
      variability of drug responsiveness and toxicity between individuals.

PMID- 15454729
TI  - Identification and characterization of the FMO2 gene in Rattus norvegicus: a good
      model to study metabolic and toxicological consequences of the FMO2 polymorphism.
AB  - BACKGROUND: In lung of many animal species flavin-containing monooxygenase 2
      (FMO2) is a 535-amino acid residues drug-metabolizing enzyme. In humans FMO2
      exhibits a genetic polymorphism. The major allele encodes a truncated FMO2, the
      minor allele a full-length FMO2. In laboratory rats we previously reported a FMO2
      gene encoding a truncated FMO2 (432-AA residues). In these strains, a double
      deletion leads to the appearance of a premature stop codon. All laboratory rat
      strains were derived from the same wild ancestor, Rattus norvegicus. METHODS: A
      PCR-based method able to specifically recognize either the wild-type or the
      mutant allele was developed to investigate a putative FMO2 polymorphism in a
      population of wild rats. The FMO2 gene was analyzed in 42 wild rats. RESULTS: A
      genetic FMO2 polymorphism similar to that described in humans was found in R.
      norvegicus. We observed three different genotypes: homozygotes for the wild-type
      FMO2 (33.3%), homozygotes for the mutant FMO2 (38.1%) and heterozygotes (28.6%).
      Comparative FMO2 mRNA and protein expressions in lungs were studied by reverse
      transcription-PCR and western blotting. FMO2 mRNA expression was identical
      between the three groups. In contrast, major differences in the expression of
      FMO2 protein were detected. FMO2 was strongly expressed in lungs of homozygotes
      for the wild-type FMO2, faintly expressed in lungs of heterozygotes and non
      expressed in lungs of homozygotes for the mutant FMO2. Comparative catalytic
      properties of lung microsomes were studied by the determination of the
      oxygenation of methimazole. FMO2 genetic polymorphism was associated with major
      differences in the S-oxidative metabolism.

PMID- 15454730
TI  - Functional polymorphism of human glutathione transferase A3: effects on
      xenobiotic metabolism and steroid biosynthesis.
AB  - The alpha class glutathione transferase GSTA3-3 is involved in steroid
      biosynthesis and the metabolism of some xenobiotics. A bioinformatics approach
      was utilized to identify novel coding region polymorphisms in the glutathione
      transferase A3 gene (GSTA3). We describe an I71L polymorphism in GSTA3 that
      occurs at a low frequency in African populations. The activity of the leucine
      containing isoform was significantly reduced in a range of glutathione
      conjugating reactions due to a diminished affinity for reduced glutathione,
      indicating that this allele could be implicated in disease caused by oxidative
      stress in steroidogenic tissue. By contrast, the delta(5)-androsten-3,17-dione
      isomerase activity of GSTA3-3 was not affected by this substitution, indicating
      that there is no direct effect on steroid synthesis. However, the L71 isoform
      displayed diminished stability at 45 degrees C. If this relative instability is
      mirrored in vivo, testosterone and progesterone synthesis may be affected in
      individuals carrying this allele.

PMID- 15454731
TI  - The effect of variable CYP3A5 expression on cyclosporine dosing, blood pressure
      and long-term graft survival in renal transplant patients.
AB  - OBJECTIVE: Cyclosporine is extensively metabolized by cytochrome-P450 3A (CYP3A)
      enzymes in the liver and intestine including the CYP3A5 isoenzyme. CYP3A5 is also
      expressed in the kidney and has been implicated in blood pressure regulation.
      Appreciable expression of CYP3A5 occurs in carriers of the CYP3A5*1 allele, while
      the CYP3A5*3 allele is associated with low expression. We tested whether the
      presence of the CYP3A5*1 allele in renal transplant recipients and in donor
      kidneys influences cyclosporine dose requirements, blood pressure and long-term
      graft survival in renal transplant patients during chronic treatment with a
      cyclosporine-based immunosuppressive regimen. METHODS: We studied 399 Caucasian
      patients from our single-center registry with stable graft function for more than
      10 weeks after transplantation. The genotypes for CYP3A5*1/*3 were determined by
      a TaqMan PCR method. Cyclosporine dose requirements, blood pressure and graft
      survival were analyzed in relation to the presence or absence of the CYP3A5*1
      allele in recipients and donor kidneys. RESULTS: The CYP3A5*1 allele was found in
      15.5% of the recipients and in 11.8% of the donor kidneys. The recipient CYP3A5*1
      allele had no effect on cyclosporine dose and blood concentrations at trough with
      and without dose-adjustment. Blood pressure, number of antihypertensive compounds
      used for treatment and graft survival evaluated by Kaplan-Meier curves and Cox
      regression analysis were also not affected by the CYP3A5*1 allele either in
      recipients or donor kidneys. CONCLUSIONS: Cyclosporine dose requirements, blood
      pressure and long-term renal graft survival are not influenced by the CYP3A5*1
      allele in Caucasian patients.

PMID- 15454732
TI  - Angiotensin II type I receptor gene and myocardial infarction: tagging SNPs and
      haplotype based association study. The Beijing atherosclerosis study.
AB  - OBJECTIVES: The present study aimed to assess the effect of haplotype variation
      in angiotensin II type I receptor (AGTR1) gene on the risk of myocardial
      infarction (MI) in Chinese males. METHODS: We used 48 patients to identify the
      putative functional polymorphisms in AGTR1 gene by direct sequencing. The program
      tagSNPs was used to identify an optimal set of tagging single nucleotide
      polymorphisms (SNPs). These selected SNPs were then genotyped in 419 male
      patients with MI and 400 age-matched male controls. The program haplo.stats was
      used to investigate the relationship between the haplotypes and MI. RESULTS:
      Sixteen polymorphisms in AGTR1 gene were identified. Based on the linkage
      disequilibrium pattern among these SNPs, six polymorphisms, SNP1, SNP6-SNP7 and
      SNP13-SNP15, were selected as haplotype tagging SNPs and further genotyped.
      Single SNP analyses indicated that the SNP1, SNP6 and SNP13 were significantly
      associated with MI, adjusted for covariates. Haplotype-based association analyses
      identified the frequency of haplotype AGATAA was lower in cases than in controls
      (P = 0.006). In comparison, three haplotypes (AAATAA, TAGCAA and AAACAG) were
      found to significantly increase the risk of MI with adjusted odds ratio equal to
      1.33, 1.75 and 2.64, respectively (P = 0.029, 0.026 and 0.015). CONCLUSIONS: Our
      study suggests that common genetic variations in the AGTR1 gene may affect the
      risk of MI in Chinese males, and that there might be several functional variants
      in AGTR1 gene and the combined effect of these variants seemed to have a larger
      effect on the risk of MI in Chinese males.

PMID- 15454733
TI  - Association between a polymorphism in cysteinyl leukotriene receptor 2 on
      chromosome 13q14 and atopic asthma.
AB  - OBJECTIVE: Cysteinyl leukotriene receptor 2 (CYSLTR2) is one of the receptors for
      the cysteinyl leukotrienes (CYSLTs), which cause bronchoconstrictions, vascular
      hyperpermeability and mucus hypersecretion in asthmatic patients. CYSLTR1
      antagonists have been shown to be effective in the treatment of chronic asthma.
      CYSLTR2 is located approximately 300 kb from D13S153, which is reportedly linked
      to asthma in several populations. We characterized the genomic structure of
      humans CYSLTR2, determined the putative major promoter region and conducted
      association studies pertaining to polymorphisms in CYSLTR2 and asthma. METHODS
      AND RESULTS: We identified three novel exons in the 5' untranslated region of
      CYSLTR2 by rapid amplification of cDNA ends and identified eight novel
      polymorphisms in CYSLTR2 by direct sequencing. A transmission disequilibrium test
      with 137 Japanese asthmatic families revealed that the -1220A > C polymorphism is
      associated with the development of asthma (P = 0.0066). In addition, a
      polymorphism in the putative promoter region caused different promoter activities
      in vitro. CONCLUSION: Our results suggest that CYSLTR2 is one of the genes that
      contributes to susceptibility to asthma in the Japanese population.

PMID- 15454734
TI  - Increased levels of aflatoxin-albumin adducts are associated with CYP3A5
      polymorphisms in The Gambia, West Africa.
AB  - OBJECTIVES: Major risk factors for hepatocellular carcinoma (HCC) are hepatitis
      viruses and exposure to aflatoxins, including aflatoxin B1 (AFB1). The mutagenic
      effect of AFB1 results from hepatic bioactivation to AFB1-exo-8,9-epoxide. This
      is in part catalysed by CYP3A5, an enzyme expressed polymorphically. We
      investigated the role of CYP3A5 polymorphisms in the formation of AFB1-exo-8,9
      epoxide in The Gambia, a population exposed to high aflatoxin levels. METHODS:
      Common CYP3A5 polymorphisms were identified in an African-American population.
      Subsequently, 288 Gambian subjects were genotyped and CYP3A5 activity predicted
      using haplotypes of the three variant loci (CYP3A5*3, *6 and *7) associated with
      decreases in protein expression. CYP3A5 expression was then compared to aflatoxin
      albumin (AF-alb) adduct, a biomarker of AFB1 bioactivation; data were also
      analysed in relation to expression of other aflatoxin-metabolizing enzymes.
      RESULTS: CYP3A5 haplotypes reflecting high CYP3A5 protein expression were
      associated with increased AF-alb. Compared to individuals with predicted low
      expression those predicted to express CYP3A5 from one allele displayed 16.1%
      higher AF-alb (95% CI: -2.5, 38.2, P = 0.093) and homozygous expressers displayed
      23.2% higher AF-alb levels (95% CI: -0.01, 52.0, P = 0.051). The effect of the
      CYP3A5 polymorphism was strongest in individuals with low CYP3A4 activity with a
      70.1% increase in AF-alb (95% CI: 11.8, 158.7, P < 0.05) in high compared to low
      expressers. A similar effect was observed for individuals with null alleles of
      GSTM1, which conjugates the AFB1-exo-8,9-epoxide to reduced glutathione.
      CONCLUSIONS: The CYP3A5 polymorphism is associated with increased levels of the
      mutagenic AFB1-exo-8,9-epoxide, particularly in individuals with low CYP3A4, and
      this may modulate individual risk of HCC.

PMID- 15454735
TI  - Identification of deletion-junction site of CYP2A6*4B allele lacking entire
      coding region of CYP2A6 in Japanese.

PMID- 15454736
TI  - A novel CYP2C9 variant that caused erroneous genotyping in a patient on warfarin
      therapy.

PMID- 15454737
TI  - Pediatric rapid sequence intubation: incidence of reflex bradycardia and effects
      of pretreatment with atropine.
AB  - BACKGROUND: The American College of Emergency Physicians (ACEP) recommends
      atropine as adjunctive therapy to prevent reflex bradycardia prior to
      laryngoscopy/tracheal intubation (L/TI) in pediatric patients. OBJECTIVE: To
      describe the incidence of reflex bradycardia and its relationship to the
      administration of atropine during L/TI in a Pediatric Emergency Department.
      DESIGN/METHODS: A retrospective cohort study was designed through review of
      records of all patients who received L/TI in the ED at an urban children's
      hospital from January 1997 to March 2001. Patients meeting inclusion criteria
      were placed into cohorts defined by whether they had received atropine prior to
      L/TI or not. RESULTS: One hundred sixty-three patients received L/TI during the
      study period. One hundred forty-three patients met inclusion criteria. Sixty
      eight patients received atropine (atropine group) prior to L/TI. Seventy-two
      percent of atropine group patients met ACEP criteria for atropine pretreatment.
      Seventy-five patients did not receive atropine pretreatment (no-atropine group).
      Forty-three percent of no-atropine group patients met ACEP criteria for
      pretreatment with atropine. The atropine group was younger [mean 22.5 vs. 36.4
      months, P = 0.003, 95% CI (-28.5, 0.70)], averaged the same number of intubation
      attempts [1.6 vs. 1.5, P = 0.941, 95% CI 0.1 (-0.3,0.4)], and had normal or
      elevated HR for age prior to L/TI (mean 159 bpm). Hypoxia occurred more often in
      the atropine group [28% vs. 16%, P = 0.046, 95% CI for difference (0.3, 27.1)].
      Bradycardia was noted in 6 patients during L/TI; 3 in the atropine group and 3 in
      the no-atropine group. CONCLUSION: Atropine is not routinely administered prior
      to L/TI in this pediatric ED. Pretreatment with atropine did not prevent
      bradycardia in all cases. These data suggest that use of atropine prior to L/TI
      may not be required for all pediatric patients. Some patients will experience
      bradycardia regardless of atropine pretreatment.

PMID- 15454738
TI  - Salbutamol via metered-dose inhaler with spacer versus nebulization for acute
      treatment of pediatric asthma in the emergency department.
AB  - OBJECTIVES: To assess the effectiveness of salbutamol delivered via a metered
      dose inhaler with spacer versus a nebulizer for acute asthma treatment in the
      pediatric emergency department. METHODS: All consecutive children younger than 14
      years old who required treatment of acute asthma exacerbation in the emergency
      department during May 2002 (prospective cohort, n = 321) and May
      2001(retrospective cohort, n = 259) were included. Inhaled salbutamol was
      administered by metered-dose inhaler with a spacer (and a face mask in children
      younger than 2 years old) in the prospective cohort and by nebulizer in the
      retrospective cohort. RESULTS: There were no significant differences between the
      two cohorts in the mean (+/-SD) age (44.50 +/- 38.64 vs. 48.37 +/- 43.55 months)
      and asthma treatment, arterial oxygen saturation (96.34 +/- 2.12% vs. 96.19 +/-
      6.32%), and heart rate (123.71 +/- 23.63 vs. 129.41 +/- 34.55 beats/min) before
      emergency department consultation. The number of doses of inhaled bronchodilators
      was also similar (1.42 +/- 1.01 vs. 1.45 +/- 0.98) as well as the number of
      children that required a stay in the observation unit, admission to the hospital,
      or returned for medical care. The overall mean length of stay in the emergency
      department was slightly shorter in the prospective cohort (82 +/- 48 vs. 89 +/-
      52 minutes). CONCLUSIONS: The administration of bronchodilators using a metered
      dose inhaler with spacer is an effective alternative to nebulizers for the
      treatment of children with acute asthma exacerbations in the emergency
      department.

PMID- 15454739
TI  - 9-1-1 responses for shopping cart and stroller injuries.
AB  - BACKGROUND: On average, 24,000 children a year are treated in the emergency
      departments (EDs) for shopping cart injuries, with over 650 children a year
      requiring hospital admission. The authors sought to evaluate the incidence and
      outcomes of children in the community evaluated by paramedics because they were
      injured in shopping cart or stroller-related incidences. METHODS: Retrospective
      design in which prehospital patients records were searched for all patients under
      14 years old who were injured in an incident involving a shopping cart or
      stroller and were responded to by paramedics. Records were reviewed for
      demographics, injury type, and disposition. RESULTS: During the 3 1/2 year study
      period, a total of 241 cases were identified with 120 being shopping cart-related
      and 121 stroller-related. The most frequent ages for stroller injuries were 0 to
      6 months and for shopping cart injuries was one year of age. Falls were the most
      common mechanism of injury, 70.3% for shopping carts and 47.5% for strollers,
      with head injuries accounting for 53% and 59% of the primary injuries in each
      group. An additional 12% and 18% suffered primary facial injuries. 77% of
      patients were transported by paramedics to an ED for evaluation, with 19% of
      parents signing out against medical advice. 8.2% were admitted to the hospital
      and there were no deaths. CONCLUSIONS: Shopping cart and stroller-related
      injuries are a common mechanism of injury for pediatric patients responded to by
      paramedics. This is an area which continued parental education is needed.

PMID- 15454740
TI  - Planning Emergency Medical Services for Children in Bolivia: part 2-results of a
      Rapid Assessment Procedure.
AB  - OBJECTIVE: To obtain social and cultural data about factors affecting the
      development of Emergency Medical Services for Children (EMS-C) in La Paz,
      Bolivia. The points-of-view of potential consumers and providers were sought.
      METHODS: A Rapid Assessment Procedure (RAP) was conducted. RAP is a qualitative
      ethnographic technique that permits delineation of social, cultural, and
      behavioral themes about a population based on members' lived experience. In-depth
      interviews and participant-observation provide rapid information and enhance the
      likelihood of successful implementation of interventions and services before
      major investments in infrastructure. RESULTS: Information collected from
      providers, administrators, and consumers revealed 4 themes affecting EMS-C: (1)
      Nature of injuries and illnesses in the Emergency Department-root causes were
      held to be related to the physical and emotional effects of poverty; (2)
      "Inappropriate" use-health care providers and consumers differed in their
      identification of valid reasons for utilizing EMS-C; (3) Coordination,
      organization, and standardization of care-both groups keenly felt their absence;
      and (4) Training and specialization-particularly the provider respondents felt
      that EMS-C would require radical changes in the training system. An expected
      theme, Prevention and Advocacy, did not emerge; respondents did not appear to
      feel that health care providers had any role in affecting public policy.
      CONCLUSIONS: RAP methodology provided a detailed picture of current EMS-C in La
      Paz, including viewpoints from all major stakeholders. This information will be
      used to support the development of Emergency Medicine programs that are locally
      driven, culturally appropriate, and socially feasible.

PMID- 15454741
TI  - Clinical experience of removing aerodigestive tract foreign bodies with rigid
      endoscopy in children.
AB  - OBJECTIVES: This study was undertaken to document the aerodigestive tract foreign
      body accidents among children, and to investigate the circumstances surrounding
      these events. METHODS: A review of the charts of pediatric patients admitted with
      the definitive or suspicious diagnosis of aerodigestive tract foreign bodies was
      carried out in the period between January 1, 1998 to December 31, 2002. RESULTS:
      There were 53 eligible children; 39 boys and 14 girls, with an age range of 7
      months to 14 years. Food items were the most common airway foreign bodies and
      coins were the most common esophageal foreign bodies. Among the 32 patients who
      underwent bronchoscopy, no foreign body was identified in 9 patients. Among the
      21 patients who underwent esophagoscopy, foreign body was removed in 19 patients.
      In 2 cases, large foreign bodies which we could not extract with forceps were
      pushed into the stomach. CONCLUSIONS: Foreign bodies in the airway and esophagus
      constitute a constant hazard in all age groups, which demands immediate approach
      and management. Although the rigid endoscopic removal of aerodigestive foreign
      bodies was successful in this series, the most effective treatment of foreign
      body accidents is their prevention.

PMID- 15454742
TI  - Elevated cardiac troponin I in a 9-week-old infant.
AB  - Myocardial ischemia in children is generally not suspected when they present to
      an emergency department with congestive heart failure. However, the opposite
      holds true for an adult patient. Elevated cardiac troponin is a specific
      biochemical marker for myocardial damage for both adults and children, however,
      they have not been routinely used in children at risk for myocardial damage. A
      case is presented of an infant with a complex congenital heart defect with
      congestive heart failure who was found to have an elevated cardiac troponin.
      Infants at risk for myocardial damage should have an evaluation of cardiac
      markers, as infants with elevated levels are prone to dysrhythmias or worsening
      cardiac function and thus warrant closer observations and therapy.

PMID- 15454743
TI  - Food allergy presenting as a "septic"-appearing infant.

PMID- 15454744
TI  - An unusual presentation of peritonsillar abscess.

PMID- 15454745
TI  - Acute hearing loss after airbag deployment.
AB  - Hearing loss from airbag deployment after motor vehicle crashes has been
      documented multiple times in the adult population, but rarely in the pediatric
      population. We report a case of significant sensorineural hearing loss following
      airbag deployment in a pediatric patient who presented to the ED on the day of
      the crash. This report highlights the need for pediatric physicians to be aware
      of the potential of minor to significant hearing loss in patients who present for
      medical evaluation after airbag deployment in motor vehicle crashes and to be
      aware of the importance of follow-up in these children.

PMID- 15454746
TI  - I woke up, "my whole stomach hurts".

PMID- 15454747
TI  - Evidence-based approach to the diagnosis of appendicitis in children.

PMID- 15454749
TI  - Preventing medical errors in pediatric emergency medicine.

PMID- 15454750
TI  - ED overcrowding-meeting many needs.

PMID- 15454751
TI  - ECGs in the ED.

PMID- 15454753
TI  - Giants and near giants in otolaryngology.

PMID- 15454752
TI  - Vestibular effects of cochlear implantation.
AB  - OBJECTIVES/HYPOTHESIS: Cochlear implantation (CI) carries with it the potential
      risk for vestibular system insult or stimulation with resultant dysfunction. As
      candidate profiles continue to evolve and with the recent development of
      bilateral CI, understanding the significance of this risk takes on an increasing
      importance. STUDY DESIGN: Between 1997 to 2001, a prospective observational study
      was carried out in a tertiary care medical center to assess the effects of
      unilateral CI on the vestibular system. METHODS: Assessment was performed using
      the dizziness handicap inventory (DHI), vestibulo-ocular reflex (VOR) testing
      using both alternate bithermal caloric irrigations (ENG) and rotational chair
      generated sinusoidal harmonic accelerations (SHA), and computerized dynamic
      platform posturography (CDP) at preoperative, 1-month, 4-month, 1-year and 2-year
      postimplantation visits. CI was carried out without respect to the preoperative
      vestibular function test results. RESULTS: Specifically, 86 patients were entered
      into the study after informed consent. For the group as a whole, pair wise
      comparisons revealed few significant differences between preoperative and
      postoperative values for VOR testing (ENG and SHA) at any of the follow-up
      intervals. Likewise, DHI testing was also unchanged except for significant
      reductions (improvements) in the emotional subcategory scores at both the 4-month
      and 1-year intervals. CDP results demonstrated substantial improvements in
      postural sway in the vestibular conditions (5 and 6) as well as composite scores
      with the device "off" and "on" at the 1-month, 4-month, 1-year, and 2-year
      intervals. Device activation appeared to improve postural stability in some
      conditions. Excluding those patients with preoperative areflexic or hyporeflexic
      responses in the implanted ear (total [warm + cool] caloric response <or= 15
      deg/s), substantial reductions (>or=21 deg/s maximum slow phase velocity) in
      total caloric response were observed for 8 (29%) patients at the 4-month
      interval. These persisted throughout the study period. These changes were
      accompanied by significant low frequency phase changes on SHA testing confirming
      a VOR insult. Of interest, no significant changes were detected in the DHI or
      CDP, and there were no effects of age, sex, device manufacturer, or etiology of
      hearing loss (HL) for these patients. CONCLUSIONS: Unilateral CI rarely results
      in significant adverse effects on the vestibular system as measured by the DHI,
      ENG, SHA, and CDP. On the contrary, patients that underwent CI experienced
      significant improvements in the objective measures of postural stability as
      measured by CDP. Device activation in music appeared to have an additional
      positive effect on postural stability during CDP testing. Although VOR testing
      demonstrated some decreases in response, patients did not suffer from disabling
      vestibular effects following CI. The mechanism underlying these findings remains
      speculative. These findings should be considered in counseling patients about CI.

PMID- 15454754
TI  - Conflicts of interest in medical publishing.

PMID- 15454755
TI  - Auditory brainstem response versus magnetic resonance imaging for the evaluation
      of asymmetric sensorineural hearing loss.
AB  - OBJECTIVES/HYPOTHESIS: Auditory brainstem response (ABR) testing and magnetic
      resonance imaging (MRI) are compared for the evaluation of patients with
      asymmetric sensorineural hearing loss (SNHL). MRI with gadolinium administration
      is the current gold standard for identifying retrocochlear lesions causing
      asymmetric SNHL. The study seeks to determine the sensitivity and specificity of
      ABR in screening for possible retrocochlear pathology. Most important among SNHL
      etiologies are neoplastic lesions such as vestibular schwannomas,
      cerebellopontine angle (CPA) tumors, as well as multiple sclerosis, stroke, or
      other rare nonneoplastic causes. The study results will allow the author to
      recommend a screening algorithm for patients with asymmetric SNHL. STUDY DESIGN:
      The study is a multi-institutional, institutional review board approved,
      prospective, nonrandomized comparison of ABR and MRI for the evaluation of
      patients with asymmetric SNHL. METHODS: Three hundred twelve patients (between
      the ages of 18 and 87) with asymmetric SNHL completed the study. Asymmetric SNHL
      was defined as 15 dB or greater asymmetry in two or more frequencies or 15% or
      more asymmetry in speech discrimination scores (SDS). These patients
      prospectively underwent both ABR and MRI. The ABR and MRI were interpreted
      independently in a blinded fashion. In addition to the ABR and MRI results, a
      variety of clinical and demographic data were collected. RESULTS: Thirty-one
      (9.94%) patients of the study population of 312 were found on MRI to have lesions
      causing their SNHL. Of the 31 patients with causative lesions on MRI there were
      24 vestibular schwannomas, 2 glomus jugulare tumors, 2 ectatic basilar arteries
      with brainstem compression, 1 petrous apex cholesterol granuloma, 1 case of
      possible demyelinating disease, and 1 parietal lobe mass. Twenty-two of the 31
      patients had abnormal ABRs, whereas 9 patients (7 with small vestibular
      schwannomas) had normal ABRs. This gives an overall false-negative rate for ABR
      of 29%. The false-positive rate was found to be 76.84%. Sensitivity of ABR as a
      screening test was 71%, and specificity was 74%. CONCLUSIONS: Ten percent of
      patients with asymmetric SNHL (by this study's criteria) are likely to have
      causative lesions found on MRI. Although the recently reported annual incidence
      of vestibular schwannoma in the general population is 0.00124%, for patients with
      asymmetric SNHL in this study, the incidence was 7.7% (nearly 4 orders of
      magnitude higher). ABR has been demonstrated to have low sensitivity and
      specificity in the evaluation of these patients and cannot be relied on as a
      screening test for patients with asymmetric SNHL. Keeping the use of MRI
      conditional on the results of ABR will annually result in missed or delayed
      diagnosis of causative lesions in 29 patients per 1,000 screened. The author
      recommends abandoning ABR as a screening test for asymmetric SNHL and adoption of
      a focused MRI protocol as the screening test of choice (within certain
      guidelines).

PMID- 15454756
TI  - Factors predicting patient perception of dysphonia caused by benign vocal fold
      lesions.
AB  - OBJECTIVES/HYPOTHESIS: To assess factors that may be predictive of patient
      perception of dysphonia severity, as quantified by the Voice Handicap Index (VHI)
      score. We hypothesize that 1) level of vocal demand; 2) auditory-perceptual
      evaluation of dysphonia severity; and 3) vocal function, as defined by phonatory
      glottal closure and mucosal wave vibration, are the most significant predictors
      of VHI score. STUDY DESIGN: : Retrospective review of 100 patients with benign
      vocal fold lesions. METHODS: Variables assessed for predictive value to VHI score
      are level of vocal demands, auditory-perceptual evaluation of dysphonia severity,
      integrity of mucosal wave vibration and phonatory glottal closure, lesion type,
      duration of current complaint, smoking, age, and sex. Harmonic to noise ratio was
      assessed in a subset of 50 patients. RESULTS: Patients with routine voice use had
      significantly lower VHI scores than those with more intensive (nonsinging/acting)
      vocal demands. Patients who quit smoking had greater VHI scores than those who
      currently smoke or never started. Patients with long-standing dysphonia tended to
      have lower VHI scores than those with shorter duration vocal complaints. Auditory
      perceptual assessment of dysphonia severity and harmonic to noise ratio were weak
      predictors of VHI score. Age, sex, lesion type, phonatory glottal closure, and
      mucosal wave vibration were not significant predictors of VHI score. CONCLUSIONS:
      Patient perception of dysphonia severity is independent of many factors commonly
      assessed during the evaluation of voice disorders. It appears to be an important
      independent element in the assessment of the effect of a benign vocal fold lesion
      and critical to therapeutic decision-making.

PMID- 15454757
TI  - Diagnosis of pneumonia with an electronic nose: correlation of vapor signature
      with chest computed tomography scan findings.
AB  - OBJECTIVES/HYPOTHESIS: The electronic nose is a sensor of volatile molecules that
      is useful in the analysis of expired gases. The device is well suited to testing
      the breath of patients receiving mechanical ventilation and is a potential
      diagnostic adjunct that can aid in the detection of patients with ventilator
      associated pneumonia. STUDY DESIGN: A prospective study. METHODS: We performed a
      prospective study of patients receiving mechanical ventilation in a surgical
      intensive care unit who underwent chest computed tomography (CT) scanning. A
      single attending radiologist reviewed the chest CT scans, and imaging features
      were recorded on a standardized form. Within 48 hours of chest CT scan, five sets
      of exhaled gas were sampled from the expiratory limb of the ventilator circuit.
      The gases were assayed with a commercially available electronic nose. Both linear
      and nonlinear analyses were performed to identify correlations between imaging
      features and the assayed gas signatures. RESULTS: Twenty-five patients were
      identified, 13 of whom were diagnosed with pneumonia by CT scan. Support vector
      machine analysis was performed in two separate analyses. In the first analysis,
      in which a training set was identical to a prediction set, the accuracy of
      prediction results was greater than 91.6%. In the second analysis, in which the
      training set and the prediction set were different, the accuracy of prediction
      results was at least 80%, with higher accuracy depending on the specific
      parameters and models being used. CONCLUSION: The electronic nose is a new
      technology that continues to show promise as a potential diagnostic adjunct in
      the diagnosis of pneumonia and other infectious diseases.

PMID- 15454758
TI  - Restoration of the orbital aesthetic subunit in complex midface defects.
AB  - OBJECTIVES/HYPOTHESIS: Although various options exist for restoration of the
      orbital defect in complex craniofacial resections, the aesthetic appearance and
      functional result of the orbit are optimized when the bony orbital architecture,
      orbital volume, and facial contour are specifically addressed. The study
      describes an approach using free tissue transfer for restoration of the native
      orbital aesthetic subunit. STUDY DESIGN: Retrospective case series. METHODS:
      Nineteen patients (male-to-female ratio, 14:5; mean age, 52 y [age range, 8-79
      y]) in the study period between 1997 and 2001 had orbital defects that could be
      classified into one of the following categories: 1) orbital exenteration cavities
      only, 2) orbital exenteration cavities with resection of less than 30% of the
      bony orbital rim, or 3) radical orbital exenteration cavities with resection of
      overlying skin and bony malar eminence. Group 1 had reconstructions with
      fasciocutaneous forearm flaps; group 2, with osseocutaneous forearm flaps; and
      group 3, with osseocutaneous scapula flaps. RESULTS: Eighteen of 19 patients
      achieved a closed orbital reconstruction with restoration of the orbital
      aesthetic subunit. Among 16 patients with more than 4 months of follow-up, 10
      patients had minimal or no resulting facial contour deformity and 8 patients
      engaged in social activities outside the home on a frequent basis. Five of the
      nine patients who were working before their surgery were able to return to work.
      CONCLUSION: Patients with complex midface defects involving the orbit can undergo
      free tissue transfer and have successful restoration of the native orbital
      aesthetic subunit without an orbital prosthesis.

PMID- 15454759
TI  - Cochlear implantation in adults with prelingual deafness. Part II. Underlying
      constraints that affect audiological outcomes.
AB  - OBJECTIVES/HYPOTHESIS: To discuss the underlying physiological and anatomical
      constraints on audiological performance of late-implanted prelingually deafened
      adult cochlear implant patients. STUDY DESIGN: Retrospective review. METHODS:
      Published literature on the topic of auditory pathway responses to prolonged
      congenital deafness was reviewed. In particular, the authors sought to identify
      the anatomical and physiological changes that take place in both the peripheral
      and central auditory pathways in response to prolonged deafness, as well as how
      they are altered by chronic electrical stimulation. RESULTS: The currently
      available evidence suggests that the colonization of the auditory cortex by other
      sensory modalities is the main limiting factor in postimplantation performance,
      not the pathological degenerative changes of the auditory nerve, cochlear
      nucleus, or auditory midbrain. CONCLUSION: The reviewed evidence, although
      circumstantial, suggests that emphasizing aurally based educational programs
      before (with hearing aids) and after cochlear implantation could reduce the
      cortical colonization phenomenon and potentially improve postimplantation
      audiological performance of patients with long-term prelingual deafness.

PMID- 15454760
TI  - Diagnosis and management of post-traumatic vertigo.
AB  - OBJECTIVES/HYPOTHESIS: Patients with post-traumatic vertigo can be difficult to
      treat secondary to the chronicity of their symptoms. Patients can have
      peripheral, central, and combined vestibular deficits. Furthermore, no
      comprehensive guidelines exist for returning these patients to work. The
      objectives of the study were to discuss diagnosis, management techniques, and
      guidelines for returning these patients to work. STUDY DESIGN: Retrospective
      analysis of a tertiary referral neurotology and balance clinic. METHODS: Between
      July 1997 and July 2003, 2390 patients with chief complaints of vertigo and/or
      dizziness were analyzed. Of these, 16 patients met the requirements for inclusion
      in the study, including head trauma and/or concussion and residual vertigo. Their
      inpatient and outpatient charts, imaging studies, audiograms, vestibular tests,
      and physical therapy evaluations were reviewed. All patients had at least 6
      months of follow-up. RESULTS: There were 5 women and 11 men, with an average age
      of 42 years. Five patients had symptoms consistent with traumatic perilymphatic
      fistulas, and two patients had symptoms consistent with post-traumatic Meniere's
      syndrome. Surgical therapy was not beneficial in relieving dysequilibrium.
      Balance testing results did not predict return-to-work status. Eleven patients
      were not allowed to return to work in any capacity, two patients were allowed to
      return to work with limited duties, and three patients were allowed to return to
      work with no restrictions. CONCLUSION: Post-traumatic vertigo can result in
      chronic symptoms. Balance testing did not predict the ability of patients to
      return to work. Surgical intervention might not control patient symptoms. Many
      patients were unable to return to work.

PMID- 15454761
TI  - Cine magnetic resonance imaging: evaluation of persistent airway obstruction
      after tonsil and adenoidectomy in children with Down syndrome.
AB  - OBJECTIVE/HYPOTHESIS: Although usually successful, not all obstructive sleep
      apnea is cured by removal of the tonsils and adenoids (T&A). This is particularly
      true in children with Down syndrome and craniofacial anomalies. This is because
      of the multiple levels of obstruction in their airways, with obstruction present
      not only at the level of the tonsils and adenoids but also from base of tongue
      obstruction, soft palate collapse, and hypopharyngeal collapse. The cine magnetic
      resonance image (MRI) is useful in evaluating the upper airway in those patients
      who have not achieved a normal polysomnogram after T&A surgery. STUDY DESIGN:
      Prospective case series. METHODS: Fifteen children with Down syndrome who had
      previously undergone a T&A but continued to have abnormal postoperative
      polysomnograms underwent a cine MRI with fast gradient cine MRI images. RESULTS:
      The cine MRI identified different areas and levels of obstruction that ultimately
      affected the children's treatment courses. Recurrent adenoid tissue,
      glossoptosis, soft palate collapse, hypopharyngeal collapse, and enlarged lingual
      tonsils were identified. The results as well as several illustrative cases are
      presented. CONCLUSION: Cine MRI evaluates upper airway obstruction in children
      who may have multiple sources of obstruction causing their obstructive sleep
      apnea. This is particularly helpful in children with Down syndrome and
      craniofacial anomalies. This technology is useful in all children with complex
      upper airway obstruction.

PMID- 15454762
TI  - Wegener's granulomatosis presenting as unilateral parotid enlargement.
AB  - OBJECTIVE: Major salivary gland enlargement is a rare presenting symptom of
      Wegener's granulomatosis. The unrecognized occurrence of this entity can delay
      diagnosis, leading to increased morbidity from disease progression. This report
      discusses the clinical features and diagnostic testing of salivary gland
      enlargement secondary to Wegener's granulomatosis to differentiate it from other,
      more common, salivary gland diseases. STUDY DESIGN: A case report of a single
      subject with unilateral parotid gland enlargement secondary to Wegener's
      granulomatosis. METHODS: A review of the clinical course, diagnostic studies, and
      histopathology related to the presenting disease. RESULTS: A 54-year-old male was
      evaluated for a 6-week history of progressive right parotid enlargement and pain
      unresponsive to antimicrobial therapy. Computed tomography scans showed diffuse,
      unilateral parotid swelling without enhancement and without a mass lesion or
      sialolith. Multiple open biopsies from the gland were necessary to demonstrate
      the presence of necrotizing granulomatous inflammation with vasculitis. Elevated
      antineutrophil cytoplasmic autoantibody, cytoplasmic pattern (c-ANCA) titers
      confirmed Wegener's granulomatosis. Hemoptysis and acute renal failure requiring
      hemodialysis developed shortly after diagnosis but eventually resolved after the
      initiation of corticosteroids and cyclophosphamide. CONCLUSIONS: Unilateral
      parotid enlargement is a rare presentation of Wegener's granulomatosis. A high
      level of clinical suspicion should prompt biopsy and testing of c-ANCA when
      initial studies or empirical treatment fails to lead to a proper diagnosis. Early
      treatment may prevent the development of other serious systemic complications
      such as renal failure.

PMID- 15454763
TI  - Temporal bone fractures: traditional classification and clinical relevance.
AB  - OBJECTIVES/HYPOTHESIS: The objectives were to evaluate the clinical relevance of
      traditional temporal bone radiographic descriptors and to investigate the
      efficacy of an alternative fracture classification scheme. STUDY DESIGN:
      Retrospective consecutive case series. METHODS: Charts and computed tomography
      scans representing 155 temporal bone fractures at a level I trauma center were
      reviewed. Fracture types were correlated with clinical presentation and outcomes.
      RESULTS: The traditional classification system (i.e., longitudinal, transverse,
      or mixed) correlated poorly with clinical findings such as facial nerve weakness
      and cerebrospinal fluid leakage. It also had limited utility in predicting
      conductive hearing loss and sensorineural hearing. An alternative schema
      distinguishing petrous from nonpetrous involvement demonstrated better
      correlation with these measures. Cerebrospinal fluid leak was 1.1 times more
      common in transverse than in longitudinal fractures but was 9.8 times more common
      in petrous than in nonpetrous fractures. Similarly, facial nerve injury more
      strongly correlated with fractures through the petrous temporal bone than did the
      other fracture types. Sensorineural hearing loss did not correlate with the
      transverse fracture classification but was significantly more prevalent in
      petrous fractures. Likewise, conductive hearing loss did not correlate with
      longitudinal fractures but was four times more common in the "middle ear"
      subcategory of nonpetrous fractures. CONCLUSION: Traditional temporal bone
      fracture descriptions correlate poorly with clinical findings. However, simply
      distinguishing petrous from nonpetrous involvement demonstrates significant
      correlation with the occurrence of serious sequelae of temporal bone fractures.
      Subcategories of mastoid and middle ear involvement further refine this
      classification schema to correlate with minor complications. This simple,
      radiographically based scheme better focuses clinical resources and attention
      toward more likely sequelae.

PMID- 15454764
TI  - Laryngeal amyloidosis in 10 patients.
AB  - OBJECTIVES: Review the location, symptoms, treatment, and outcomes in 10
      consecutive laryngeal amyloid (LA) patients. STUDY DESIGN: Pre and retrospective
      evaluation after treatment. METHODS: Analysis of visual and phonatory pathology
      and detailed description of surgery. RESULTS: Amyloid on the undersurface of both
      true vocal cords (TVCs) was found in two cases, uni- or bilaterally submucosally
      in the false vocal cords (FVCs) in eight cases, extending down into the lateral
      TVC in four cases, or on the undersurface of the TVCs as well in one case. The
      chief complaint was hoarseness and not shortness of breath. The amyloid was
      resected with a CO2 laser by way of microdirect laryngoscopy (MDL) on one side at
      a time to try to prevent anterior commissure scarring. Removal of most of the FVC
      improved the voice, but removal of the whole FVC to the inner thyroid
      perichondrium was found to be necessary to avoid recurrence from supraglottic
      deposits. Removal of at least 2 mm of the upper edge of a 3 to 4 mm thick
      submucosal deposit to the thyroarytenoid (TA) muscle along with the overlying
      mucosa on at least one side was necessary to improve hoarseness when amyloid was
      present on the undersurface of both TVCs. Partial regrowth occurred in a few
      months to years after partial removal. Seven patients had had one to seven prior
      removals. Any hard amyloid in the lateral TVC (floor of ventricle) as an inferior
      extension from FVC amyloid needed to be at least partially removed to avoid
      hoarseness from a convex vocal cord. The voice improved postoperatively in all
      patients. Follow-up after the first operation was 6 months to 16 years, with an
      average of 6.5 years. Four FVC patients required re-excision on the same side
      after the first operation, but none has required a third removal as of yet.

PMID- 15454765
TI  - Central effects of residual hearing: implications for choice of ear for cochlear
      implantation.
AB  - OBJECTIVES/HYPOTHESIS: The study tested the hypothesis that among patients with
      similar levels of residual hearing in the nonimplanted ear, speech perception
      outcome is the same whether or not the implanted ear has profound or severe
      levels of hearing loss. STUDY DESIGN: Retrospective. METHODS: Levels of hearing
      loss in postlingually deafened adults who had cochlear implantation at Johns
      Hopkins University (Baltimore, MD) between 1991 and 2002 were classified
      according to pure-tone averages as bilateral severe (n = 20), severe-profound
      (severe in one ear and profound in the other) (n = 23), and bilateral profound (n
      = 43). There was no significant difference in the age at onset and duration of
      deafness among the three patient groups. Individuals in the bilateral severe and
      severe-profound groups had comparable levels of severe hearing loss in their
      nonimplanted ears, whereas those in severe-profound and bilateral profound groups
      had comparable levels of profound hearing loss in their implanted ears. Speech
      perception performance was evaluated using words from the Consonant Nucleus
      Consonant word list, Hearing in Noise Test sentences in quiet, and Central
      Institute for the Deaf sentences through recorded presentation at 70 dB sound
      pressure level (SPL). RESULTS: Despite the profound hearing loss of the implanted
      ear in the asymmetrical group, there was no significant difference in mean speech
      perception scores compared with the bilateral severe group within the first year
      after implant surgery. By comparison, the bilateral profound group had lower
      speech perception results compared with patients with residual hearing in one or
      both ears. CONCLUSION: The study results suggest that implantation of the
      profoundly deafened ear does not diminish the functional advantage conferred by
      residual hearing in a patient with asymmetrical hearing loss. Therefore, the
      central auditory pathway may be the site at which persistent auditory function
      has its most beneficial effects.

PMID- 15454766
TI  - Role of intrathyroidal calcifications detected on ultrasound as a marker of
      malignancy.
AB  - OBJECTIVES: Clinically palpable thyroid nodules are present in between 4% and 7%
      of the population, with only a small percentage of those harboring malignancy.
      Thus, it is important to find a cost-effective way to determine which nodules are
      more likely to be malignant. The purpose of this study was to evaluate the use of
      intrathyroidal calcifications detected on ultrasound as a risk factor for
      malignancy. STUDY DESIGN: Retrospective chart review. METHODS: One hundred fifty
      nine patients with thyroid disease were included in this study. Patients were
      selected from a thyroid ultrasound (TUS) database. Charts were then reviewed, and
      only those patients who had a preoperative TUS and underwent surgery for tissue
      diagnosis were included. RESULTS: Of the 159 patients, 66 (41.5%) were diagnosed
      with cancer. Of those with malignancy, 52 (78.8%) had calcifications noted on
      TUS. Ninety-three of the patients were diagnosed with benign pathology. Of those
      93 patients, 36 (38.7%) had TUS findings consistent with calcifications, whereas
      57 (61.3%) did not. Statistical analysis using a chi-square test showed a strong
      association between cancer status and calcification, with P <.001. In our study,
      calcifications on TUS had a sensitivity of 78.8% and a specificity of 61.3%, with
      an odds ratio of 5.88. CONCLUSION: The presence of calcifications detected on TUS
      should alert the physician for the possibility of malignancy, and further work-up
      should be pursued. This information may be used to improve the sensitivity of
      other diagnostic tests such as fine needle aspiration biopsies. Given the
      relatively low sensitivity and specificity of the test, its use alone as a marker
      of malignancy is limited, but it may be used in combination with other known risk
      factors and tests to decide on the most appropriate treatment plan.

PMID- 15454767
TI  - Tamoxifen therapy for Riedel's thyroiditis.

PMID- 15454768
TI  - Pediatric hemophilic pseudotumor of the paranasal sinus.
AB  - OBJECTIVES/HYPOTHESIS: Hemophilic pseudotumors are rare clinical entities in
      otolaryngology. An unusual case of a pediatric hemophilic pseudotumor of the
      paranasal sinus in a previously undiagnosed hemophiliac is presented. STUDY
      DESIGN: Case report. METHODS: A 6-month-old, otherwise healthy boy was admitted
      for evaluation of a rapidly expanding left-sided cheek mass. The patient's
      initial presentation, imaging workup, and intraoperative and postoperative
      courses are discussed. RESULTS: Imaging workup revealed a large, heterogeneous,
      dense lesion in the patient's left-side maxillary sinus with distortion of the
      orbital floor and hard palate. Because of the concern for an aggressive
      malignancy, a biopsy was performed. After a Caldwell-Luc approach, a large amount
      of greenish fluid leaked from an otherwise empty maxillary sinus. The patient
      continued to bleed from his intraoral incision postoperatively and required two
      packed erythrocyte transfusions. Subsequent hematological testing led to a
      diagnosis of severe hemophilia type A with factor VIII levels less than 1% of
      normal. After treatment with recombinant coagulation factors hemostasis was
      achieved, and the patient clinically improved. CONCLUSION: The study presents the
      first report of a pediatric hemophilic pseudotumor in the paranasal sinuses
      leading to a diagnosis of hemophilia. It is a rare entity characterized by a
      cycle of repeated hemorrhage with subsequent encapsulation of the coagulum
      leading to pressure-induced distortion of adjacent bone. In the correct clinical
      setting, hemophilic pseudotumor should be considered in the differential
      diagnosis of a rapidly expanding mass in children.

PMID- 15454769
TI  - A study on the frequency of olfactory dysfunction.
AB  - OBJECTIVES/HYPOTHESIS: Goals of the study were to evaluate the frequency of
      olfactory dysfunction in a large representative population without sinonasal
      complaints and to investigate the extent to which general pathological
      conditions, medications, and aging influence olfaction. STUDY DESIGN:
      Prospective. METHODS: Results based on an odor identification test ("Sniffin'
      Sticks") were reported from 1240 subjects. The subjects presented themselves to
      an otorhinolaryngology outpatient clinic with relatively mild and transitory
      complaints unrelated to the upper airways. A detailed otorhinolaryngological
      examination in combination with a standardized interview further ascertained that
      these patients had no rhinological problems or symptoms relating to sinonasal
      disease. RESULTS: Apart from the confirmation of the effects of age, gender, and
      certain otorhinolaryngological diseases on the sense of smell, the study results
      revealed that certain general diseases (liver diseases, nonotolaryngological
      cancers) appear to influence olfactory function, whereas other diseases or
      disorders have little or no impact on olfaction (hypertension, cardiovascular
      problems). CONCLUSION: The data in the study revealed that olfactory dysfunction
      among subjects under 65 years of age is more frequent than previously reported.

PMID- 15454770
TI  - Malignant odontogenic tumors: a 22-year experience.
AB  - OBJECTIVES/HYPOTHESIS: Malignant odontogenic tumors are exceedingly rare and
      arise from odontogenic epithelial residues and odontogenic cysts in the jaw
      bones. Odontogenic malignancies have various origins. Some develop directly from
      the remnants of odontogenic epithelium left after completion of dental
      development; others may result from malignant transformation of a benign
      odontogenic cyst or ameloblastoma. These lesions are usually locally aggressive
      with radical surgery being the primary mode of treatment. Because of their
      rarity, much of the existing information about malignant odontogenic tumors with
      regard to their origin, clinicopathological features, biological behavior, and
      therapeutics is derived from case reports or small series. The study represents
      one of the largest series of malignant odontogenic tumors compiled in a single
      institution. STUDY DESIGN: Retrospective 22-year review from an Academic Medical
      Center. METHODS: Twenty cases of reported malignant odontogenic tumors were
      diagnosed in the authors' institution between 1981 and 2002. All pathological
      slides were reviewed to reconfirm diagnosis. Malignancy was confirmed based on
      the following criteria: histological findings of infiltrative growth, atypical
      cytological features, and focal necrosis or clear evidence of distant metastatic
      spread. Patient age, race, sex, treatment and outcome were recorded on chart
      review. RESULTS: Of the twenty reported cases, only nine were actually found to
      be malignant tumors on re-evaluation. These consisted of four cases of malignant
      ameloblastomas, two cases of ameloblastic carcinoma, one case of malignant
      Pindborg tumor (calcifying epithelial odontogenic tumor), one case of odontogenic
      ghost cell carcinoma, and one case of squamous cell carcinoma arising in an
      odontogenic keratocyst. The racial demographics were six Caucasian patients, one
      African American patient, and two Asian patients; seven men and two women
      represented the gender distribution. Tumors of six cases were located in the
      mandible, and of three cases, in the maxilla. All cases were treated with radical
      surgical excision. Two patients died of their disease, three patients were alive
      and free of disease, and four patients were lost to follow-up. CONCLUSION:
      Malignant odontogenic tumors are rare. They require a multidisciplinary team to
      determine proper treatment. Long-term surveillance is mandatory and is
      accomplished by routine physical examinations, along with serial radiographic
      imaging.

PMID- 15454771
TI  - Effects of ascorbic acid on oxidative system and transient evoked otoacoustic
      emissions in rabbits exposed to noise.
AB  - OBJECTIVES/HYPOTHESIS: The objective was to investigate the effects of both noise
      exposure and ascorbic acid on oxidative status and hearing thresholds of rabbits.
      STUDY DESIGN: Randomized prospective animal study comparing oxidative parameters
      and otoacoustic emissions in two rabbit groups exposed to noise. One group was
      given ascorbic acid, the other group was not given any treatment. METHODS: Two
      groups of rabbits were used in the study; each group had six rabbits. The six
      rabbits in the first group were not given any treatment, whereas 500 mg
      intramuscular ascorbic acid twice daily for 2 1/2 days was given to the six
      rabbits in the second group. Transient evoked otoacoustic emissions were recorded
      in all animals before and after noise exposure. Total protein sulfhydryl groups,
      carbonyl contents, and malondialdehyde levels, as well as erythrocyte
      glutathione, superoxide dismutase, and catalase enzyme levels, were measured in
      all rabbits. All the rabbits were exposed to noise (100 dB sound pressure level,
      1000 Hz, 1 h), and transient evoked otoacoustic emissions were recorded again.
      RESULTS: When oxidative parameters before noise exposure were compared,
      erythrocyte glutathione and catalase enzyme levels were detected to be higher in
      the second group (P <.05). In the first group of rabbits after noise exposure,
      total protein sulfhydryl groups were found to be reduced (P <.05), whereas plasma
      carbonyl contents and malondialdehyde levels were elevated significantly (P
      <.05). In this group, erythrocyte glutathione, superoxide dismutase, and catalase
      enzyme levels were low (P <.05). In the second group, which was given ascorbic
      acid, total protein sulfhydryl groups were reduced (P <.05), whereas plasma
      carbonyl contents and malondialdehyde levels did not change (P >.05) following
      noise exposure. In the second group, erythrocyte glutathione and catalase enzyme
      levels were reduced (P <.05), but superoxide dismutase levels did not change (P
      >.05). Transient evoked otoacoustic emissions after noise exposure were weak in
      both groups, but reproducibility and signal-to-noise ratios were higher in the
      second group (P <.05). CONCLUSION: Ascorbic acid treatment inhibited both lipid
      peroxidation and oxidative damage of proteins in rabbits exposed to noise. The
      study data suggest, at least, that oxidative status should be included in the
      physiopathology of noise-induced hearing loss; in addition, a brief application
      of ascorbic acid before noise exposure appeared to play a protective role for
      cochlea.

PMID- 15454772
TI  - Amplitude effects on electrocochleography outcomes.
AB  - OBJECTIVE: Electrocochleography measures in humans were examined to determine
      factors affecting results. STUDY DESIGN: Retrospective study. METHODS: Analysis
      was performed on data from 479 patients seen from 1998 to 2002 who underwent
      electrocochleography with a tympanic membrane electrode. Measures from click
      evoked electrocochleography (the summating potential to action potential ratio
      [SP/AP]) were compared with tone evoked electrocochleography (the SP amplitude).
      RESULTS: Findings indicate a strong correlation between click and tone measures
      if the AP from click measures was over 1 microV (P <.001), but no significant
      correlation between these measures if the AP was under 1 microV. Results were
      also analyzed with respect to patient hearing sensitivity and final diagnosis.
      CONCLUSION: Tympanic membrane electrocochleography is more efficacious when the
      AP from click stimulation is over 1 microV.

PMID- 15454773
TI  - Bag-1 expression as a prognostic factor in tongue squamous cell carcinomas.
AB  - OBJECTIVES: To investigate the prognostic significance of the antiapoptotic
      protein Bag-1. In addition, the relationship between Bag-1 expression, other
      apoptosis-related and proliferative parameters. STUDY DESIGN: Eighty-five
      randomly selected patients with T1 to T4 oral tongue squamous cell carcinomas
      (SCC) were studied. METHODS: Sections from diagnostic, formalin-fixed, paraffin
      embedded specimens were stained immunohistochemically to detect Bag-1 protein.
      RESULTS: Bag-1 expression correlated positively with apoptosis-related parameters
      such as Bcl-2 expression (P =.001) and proliferation-related parameters including
      Ki-67, mean argyrophilic nucleolar organizer regions (mAgNOR), and the percentage
      of AgNOR (pAgNOR) (P =.0117, P =.0257, and P =.0008, respectively). Correlation
      with Bag-1 expression and T classification (P =.0362), N classification (P
      =.0284), and clinical stage (P =.0117) was also found. In addition, Bag-1
      expression was associated with the carbohydrate epitopes H-antigen and Le (P
      =.0004 and P =.0011, respectively). No correlation was found between Bag-1
      expression and p53 accumulation, Bax expression, or apoptotic index (AI).
      However, a combined score of Bcl-2 and Bag-1 expression was inversely associated
      with AI (P =.046). Patients with tumors expressing high Bag-1 values had a
      shortened disease-specific survival time when compared with those with low Bag-1
      values (P =.0017). A two-parameter combination between Bag-1 expression and Bax
      expression or AI, respectively, revealed an enhanced prognostic potential (P
      <.0001) when compared with single parameters. CONCLUSION: Correlation between Bag
      1 expression and other biologic variables revealed that Bag-1 might be involved
      in several biologic processes including apoptosis and cell proliferation. The
      expression of Bag-1 protein, particularly in combination with Bax expression or
      AI, respectively, has prognostic value in oral tongue SCC.

PMID- 15454774
TI  - Early development of the nose in human embryos: a stereomicroscopic and
      histologic analysis.
AB  - OBJECTIVES/HYPOTHESIS: To analyze the morphologic features of the nose in the
      human embryo from the 4th to 8th developmental week according to Carnegie stage.
      STUDY DESIGN: Stereomicroscopic and histologic analysis of the morphology of the
      human embryo. METHODS: A total of 27 cases of embryos, ranging from Carnegie
      stage 13 to 23, were analyzed. The external morphology was observed with a
      stereomicroscope, photographed, and analyzed. The histologic features were
      observed with a light microscope in the horizontally transected specimens stained
      with hematoxylin-eosin. RESULTS: The nasal placode was observed in stage 13, and
      it became flat or even concave in stage 14. In stage 15, the nasal pit was
      formed. In stage 16, the nasal sac and nasal fin were observed. In stage 17, the
      oronasal membrane was formed by thinning of the nasal fin. In stage 18, the
      primitive choana was established by a rupture of the oronasal membrane. In stage
      19, the lateral palatine process projected vertically below the level of the
      tongue. The cartilaginous nasal capsule was formed in stage 20. In stage 21, the
      olfactory area was localized to the upper portion of the lateral nasal wall and
      the nasal septum. In stage 22, the lateral palatine process developed in a
      somewhat horizontal orientation. In stage 23, the premaxilla and primitive choana
      were formed. CONCLUSIONS: The development of the nose is most active from
      Carnegie stage 13 to 19, which corresponds to the end of the fourth embryonic
      week to the end of the seventh week. Thus, this period is considered to be the
      most important period in human nasal embryonic development.

PMID- 15454775
TI  - Assessment of salivary flow rate: biologic variation and measure error.
AB  - OBJECTIVE: To investigate the applicability of the swab method in the measurement
      of salivary flow rate in multiple-handicap drooling children. To quantify the
      measurement error of the procedure and the biologic variation in the population.
      STUDY DESIGN: Cohort study. METHODS: In a repeated measurements design, a
      baseline series of salivary flow rates were obtained from 45 children. The within
      subject SD (SW) was calculated to express the measurements error according to a
      procedure introduced by Bland and Altman. RESULTS: Two hundred twenty-four
      samples (mean 0.40 mL/min, SD 0.19 mL/min) were obtained and analyzed. The
      results of this study indicate that consistent scores were obtained at subsequent
      measurements, and good parity existed between the two measurements of salivary
      flow rate at each session. The SW could be estimated (0.11 mL/min), which was
      applied to quantify the specific variation of the salivary flow rate in our
      population. CONCLUSION: According to Bland and Altman, the SW, which is a
      quantification of the measurement error and biologic variation, was found to be a
      useful tool to evaluate the obtained baseline salivary flow rate measurements.
      The swab method can be used to evaluate salivary flow rates in drooling children
      with cerebral palsy during interventional studies that aim to reduce saliva
      production.

PMID- 15454776
TI  - OK-432 therapy for cervical lymphangioma.
AB  - OBJECTIVE: To describe our experience with sclerosing treatment of lymphangiomas
      in the head and neck region by intralesional injections of OK-432. STUDY DESIGN:
      Case series. METHODS: Patients with the diagnosis of a macrocystic-type cervical
      lymphangioma were treated by one to three intralesional injections of OK-432
      (0.01 mg of OK-432/1 mL of lymphangioma fluid, up to a maximum of 0.2 mg in the
      first injection and 0.3 mg in the second or third injections). All injections
      were performed under ultrasound guidance. Children were injected under sedation.
      RESULTS: Eleven patients were treated with injections of OK-432: 7 children and 4
      adults. They were followed up for a period of 5 to 68 (mean 30) months. Eight
      (73%) patients had complete or subcomplete resolution of the lymphangioma after
      one or two injections. In three (27%) cases, no response was obtained (2 cases)
      or the lymphangioma recurred (1 case) after two to three injections. In two
      cases, surgical excision was performed. There was no evidence of fibrosis around
      the cysts. There were no complications to OK-432 injections. CONCLUSION:
      Intralesional injection of OK-432 is an effective treatment modality for
      macrocystic-type lymphangiomas in the head and neck region. It has no
      complications, and surgical excision in case of failure is not compromised by
      fibrosis. Sclerosing of macrocystic-type lymphangiomas with OK-432 should
      therefore be considered before surgical excision.

PMID- 15454777
TI  - Quality and safety in a complex world: why systems science matters to
      otolaryngologists.
AB  - Almost all modern medical care is delivered in the setting of many overlapping
      systems. Each system may consist of multiple providers and in most cases
      electronic and mechanical components. Even "simple" outpatient care is delivered
      by teams of providers, administrators, and devices. Critically ill inpatients are
      cared for in extraordinarily complex systems with hundreds of human and non-human
      elements. The science of complex systems has exploded in recent decades, and
      there is a large body of knowledge about how such systems function effectively or
      ineffectively. Many principles of systems science are simple to understand and
      apply, but few Otolaryngologists are well educated about them. A basic knowledge
      of systems science will greatly improve the Otolaryngologist's ability to
      function in complex health care systems and to provide the best care for his or
      her patients.

PMID- 15454778
TI  - Predicting decannulation outcomes after distraction osteogenesis for syndromic
      micrognathia.
AB  - OBJECTIVES: To characterize the airway anatomy by upper endoscopy in children
      with syndromal mandibular hypoplasia and to determine whether predistraction
      endoscopy is predictive of the likelihood of successful outcomes after mandibular
      distraction. STUDY DESIGN: Retrospective chart review. METHODS: Assessment of the
      upper airway by subsites was qualitatively extrapolated into a devised 4-point
      scale. Upper airways were characterized and evaluated in patients on the basis of
      decannulation outcomes after distraction. RESULTS: Of the 20 patients, 12 were
      decannulated, and 6 remain tracheostomy dependent. The average compiled
      preoperative airway obstruction scores in decannulated patients (2.25) compared
      with those who failed decannulation (2.36) was not statistically significant (P
      =.291). A significant change after distraction was noted only at the levels of
      the oropharynx and supraglottis (P <.001). The average airway scores at these
      subsites in decannulated patients improved from a mean of 3.46 to 2.17 (P =.002).
      In patients who failed decannulation, the pre- and postdistraction scores also
      improved from 3.92 to 2.50 (P =.026). Analysis of the average postdistraction
      airway scores in decannulated patients (2.17) compared with failures (2.5) failed
      to reveal a significant difference (P =.375), suggesting that some patients
      remain tracheostomy dependent despite adequate mandibular expansion. Preoperative
      airway scores in the two groups were statistically equivocal and, therefore, not
      predictive of the likelihood of decannulation. CONCLUSIONS: Preoperative airway
      endoscopy alone is not predictive of the likelihood of successful decannulation
      after distraction osteogenesis. Comparison of the airway patency after
      distraction revealed statistically equivocal airway caliber, suggesting that some
      children fail to advance to decannulation despite adequate mandibular
      distraction.

PMID- 15454779
TI  - Immunoglobulin E to staphylococcal and streptococcal toxins in patients with
      chronic sinusitis/nasal polyposis.
AB  - BACKGROUND: The role of infectious agents and their contribution to the
      inflammation in chronic sinusitis/nasal polyposis (CS/NP) is not clear.
      Staphylococcal and streptococcal toxins have superantigen activity and have been
      implicated in inflammatory conditions such as atopic dermatitis, psoriasis, and
      asthma. OBJECTIVE: We investigated the presence of immunoglobulin (Ig)E
      antibodies to staphylococcal and streptococcal toxins in the serum of individuals
      with CS/NP. METHOD: IgE antibodies to staphylococcal exotoxins, A, B, and toxic
      shock syndrome toxin-1 and streptococcal pyrogenic exotoxin A, B, and C were
      measured in 23 individuals with CS/NP before functional endoscopic sinus surgery
      and in controls (7 atopic and 6 nonatopic) individuals without chronic sinusitis.
      Presence of IgE to the toxins was also correlated with disease severity on sinus
      computed tomography (CT) scans. RESULTS: Staphylococcal and streptococcal toxin
      specific IgE antibodies were detected in 18 of 23 (78%) and 7 of 21 (33.3%)
      patients, respectively. None of the controls had IgE to the staphylococcal or
      streptococcal toxins (P <.0001). There was no association between radiographic
      severity of sinus disease and the presence of IgE antibody to the toxins.
      CONCLUSION: A significantly greater proportion of CS/NP patients had IgE to
      staphylococcal or streptococcal toxins. Evidence of IgE antibodies directed
      against staphylococcal and streptococcal toxins in the sera of patients with
      CS/NP suggests a potential role of these toxins with established superantigen
      effects in the pathogenesis of CS/NP.

PMID- 15454780
TI  - mRNA for genes associated with antigen presentation are expressed by human middle
      meatal epithelial cells in culture.
AB  - OBJECTIVES/HYPOTHESIS: Although the mechanisms underlying the initiation and
      maintenance of inflammation in chronic rhinosinusitis are poorly understood, the
      activation of memory T cells within the nasal mucosa is thought to play an
      important role. T-cell activation requires specialized antigen processing and
      presentation of antigen by immunocompetent cells in the context of cell surface
      immune molecules. The purpose of this study was to investigate the expression of
      such molecules by human sinonasal epithelial cells grown in culture at the air
      liquid interface (ALI). METHODS: Middle meatal epithelium was obtained from six
      patients undergoing endoscopic sinus surgery. Dissociated epithelial cells were
      grown to confluence in serum-free, defined medium and transferred to filter
      inserts for culture at the ALI. Cells were harvested at 2 and 21 days of growth
      at the ALI and processed for real-time polymerase chain reaction (PCR). The
      presence and relative abundance of constitutively expressed mRNA for human
      leukocyte antigen (HLA)-B, HLA-DR, B7 to 1, B7 to 2, B7-H2, B7-H3, and cathepsin
      D were assessed. RESULTS: After 2 days at the ALI, middle meatal epithelial cells
      demonstrated expression of genes for each of the antigen processing associated
      genes tested. The expression of HLA-B and HLA-DR increased significantly with
      cellular maturation at the ALI. Expression of HLA-DR and B7 to 1 increased with
      cytokine stimulation. CONCLUSIONS: Primary human epithelial cells obtained from
      the middle meatus express genes associated with antigen presentation function.
      The pattern of gene expression is modulated by cytokine stimulation and changes
      as the cells differentiate at the ALI. These findings suggest that mature middle
      meatal epithelial cells have the cellular machinery to interact with T cells and
      therefore may be direct participants in the modulation of T-cell activity in
      chronic sinusitis.

PMID- 15454781
TI  - Endoscopic management of cerebrospinal fluid rhinorrhea.
AB  - PURPOSE: Most anterior skull base defects causing cerebrospinal fluid (CSF)
      rhinorrhea can be readily approached using endoscopic techniques when surgical
      repair is necessary. We present our data from endoscopic repair of CSF rhinorrhea
      with long-term follow-up. METHODS: Retrospective data analysis of patients that
      were diagnosed with anterior skull base CSF rhinorrhea and underwent endoscopic
      repair at a tertiary institution. Data were analyzed to determine the etiology
      and location of CSF leaks. Diagnostic techniques, surgical techniques, and
      surgical outcomes were reviewed. RESULTS: Ninety-two patients were diagnosed with
      CSF rhinorrhea and underwent endoscopic repair over a 12-year period. Forty-eight
      were males, and 44 were females. The average age was 49 (range 6-81) years.
      Average follow-up was 25 months, with a range of 12 to 82 months. The etiology of
      CSF leak was prior endoscopic sinus surgery in 23 patients (25%), idiopathic in
      19 (21%), neurosurgery in 17 (18%), trauma in 18 (20%), and the presence of
      meningocele/encephalocele in 11 patients (12%). The most common location of the
      defect was the sphenoid sinus (n = 36, 39%), followed by ethmoid roof (n-27,
      29%), and cribriform plate (n = 24, 26%). Endoscopic repair was initially
      successful in 78 (85%) patients. Seven additional patients underwent successful
      revision endoscopic repair for an overall success rate of 92% (n = 85). Five (6%)
      large skull base defects were eventually repaired by neurosurgery using open
      intracranial techniques. No major complications were encountered. CONCLUSION: The
      intranasal endoscopic approach is an effective and safe technique in the surgical
      management of anterior skull base CSF rhinorrhea. Long-term success rate in our
      patient population was 92%.

PMID- 15454782
TI  - Relationships of craniofacial morphology and body mass index with sleep
      disordered breathing in Japanese men.
AB  - OBJECTIVE/HYPOTHESIS: Obesity is an established risk factor for sleep-disordered
      breathing, but the impact of craniofacial morphology is uncertain. The aim of
      this study was to assess the impact of craniofacial morphology and body weight on
      sleep-disordered breathing in Japanese men. STUDY DESIGN: A cross-sectional
      study. METHODS: We measured body mass index, seven cephalometric variables, and
      3% oxygen desaturation index recorded by a pulse oximeter in 313 Japanese men
      aged 20 to 65 years who attended a sleep clinic. We defined craniofacial score as
      the sums of quartile points (0-3) for distance from sella to nasion and that from
      hyoid bone to mandibular plane. RESULTS: The mean value of 3% oxygen desaturation
      index and odds ratios of 3% oxygen desaturation index 15 or greater progressively
      increased with craniofacial score as well as body mass index. Multivariate odds
      ratios associated with craniofacial score were higher in men with body mass index
      25.0 kg/m or greater (odds ratio = 4.2, 95% confidence interval [CI] = 2.1-8.6)
      than in men with lower body mass index (odds ratio = 1.6, 95% CI = 0.7-3.6).
      CONCLUSIONS: Our results imply the importance of cephalometric assessment in
      overweight patients.

PMID- 15454783
TI  - Stress as a trigger of attacks in Meniere's disease. A case-crossover study.
AB  - BACKGROUND: Meniere's disease is defined as the presence of recurrent,
      spontaneous episodic vertigo, hearing loss (HL), aural fullness, and tinnitus.
      The occurrence of attacks is unpredictable. The etiology is still unknown, but
      the disease has a pathologic correlate in hydropic distension of the
      endolymphatic system. Earlier studies have shown increased incidence of stress on
      the same day as vertigo attacks, but it has not been determined whether stress
      occurring on the day of the vertiginous episode came before or after the onset of
      the vertigo. METHODS: A case-crossover study including 46 patients with active
      Meniere's disease. MAIN OUTCOME MEASURE: Relative risks with 95% confidence
      intervals (CI). FINDINGS: During the study period, 153 Meniere's attacks were
      reported. Twenty-four (52%) of the 46 patients reported attacks. Twelve of the
      153 (8%) attacks occurred within 3 hours after exposure to emotional stress. The
      relative risk of having an attack was 5.10 (95% CI 2.37-10.98) during 3 hours
      after being exposed to emotional stress. Twenty-nine percent of the patients with
      attacks had at least one attack after exposure to emotional stress. For mental
      stress, the relative risk was 4.16 (95% CI 1.46-11.83) and the hazard period 1
      hour, but only five attacks were exposed. No excess risk was found after physical
      stress. INTERPRETATION: Being exposed to emotional stress increases the risk of
      getting an attack of Meniere's disease during the next hour, and the hazard
      period is possibly extended up to 3 hours.

PMID- 15454784
TI  - Measuring quality of life in children with adenotonsillar disease with the Child
      Health Questionnaire: a first U.K. study.
AB  - OBJECTIVE: To validate the Child Health Questionnaire (CHQ) and assess the
      quality of life of inner-city British children with adenotonsillar disease.
      METHODS: The primary caregiver of a consecutive series of 43 patients referred
      for adenotonsillar disease to a pediatric otolaryngology clinic completed the
      Child Health Questionnaire. Questionnaires were analyzed for data quality and
      completeness, items/scale correlation, internal consistency and discriminant
      validity, interscale correlation, reliability estimates and external validity.
      RESULTS: CHQ demonstrated excellent measuring characteristics in our population.
      In a comparison with healthy children, 11 out of 15 measures of quality of life
      were significantly depressed in our sample. Compared with children with
      rheumatoid arthritis, scores were equivalent in most areas, with the exception of
      the global health subscale and overall physical score, where our sample scored
      significantly lower. CONCLUSION: The CHQ (PF 28 version) is an accurate and
      reliable way of assessing the impact of adenotonsillar disease on the quality of
      life in children in Britain. This appears to be quite significant in most aspects
      of a child's life.

PMID- 15454785
TI  - Reduction of salivary flow with botulinum toxin: extended report on 33 patients
      with drooling, salivary fistulas, and sialadenitis.
AB  - OBJECTIVES/HYPOTHESIS: The aim of the study was the evaluation of the clinical
      data of 33 patients who had had drooling attributable to various diseases,
      salivary fistulas, and sialadenitis and had been treated with injection of
      botulinum toxin type A (Botox). A controlled follow-up study documenting
      efficiency, possible side effects, and duration of the effect of treatment was
      also performed. STUDY DESIGN: Retrospective clinical evaluation. METHODS: Thirty
      three patients with drooling attributable to head and neck carcinoma,
      neurodegenerative diseases, stroke, or idiopathic hypersalivation or with
      salivary fistula or chronic sialadenitis received injections of 20 to 65 U
      botulinum toxin type A into salivary glands under sonographic control. The entire
      salivary flow rate and the output per minute of the salivary analytes
      thiocyanate, total protein, alpha-amylase, acid phosphatase, kallikrein, and
      immunoglobulin A were measured at various times before and after injection. The
      patients were examined with regard to severity of their symptoms, including
      sonographic control investigation of their cephalic salivary glands. RESULTS:
      Twenty-six patients (79% of all patients) reported a distinct improvement of
      their symptoms after toxin injection. Seven patients noted a return of high
      salivation rates and requested a second injection after 4 to 7 months. Duration
      of toxin effect varied widely among individuals. In general, salivary flow rates
      and thiocyanate output dropped sharply within 1 week after injection and had
      increased again after a period of 12 to 16 weeks. Conversely, amylase outputs
      increased during this period, whereas the outputs of the other analytes remained
      roughly constant. Sonography did not reveal any major changes in salivary gland
      parenchyma, and side effects were not noted. CONCLUSION: Reduction of salivary
      flow in patients with drooling, salivary fistulas, or chronic sialadenitis by
      local injection of botulinum toxin type A into the salivary glands proved to be a
      dependable therapy for these disorders, as shown in the present extended report
      on 33 patients. Side effects were not observed. The effect of toxin application
      lasted for approximately 3 months. Based on their results, the authors recommend
      botulinum toxin injection as the therapy of choice in patients with the problem
      of drooling.

PMID- 15454786
TI  - A new approach to the reconstruction of extensive congenital midline nasal
      defects.

PMID- 15454787
TI  - Microstereo-laryngoscopic lipoinjection: practical considerations.

PMID- 15454788
TI  - Extensive supraclavicular dissection for thyroid malignancy.

PMID- 15454789
TI  - Integrating emergency general surgery with a trauma service: impact on the care
      of injured patients.
AB  - BACKGROUND: There has been considerable discussion on the national level on the
      future of trauma surgery as a specialty. One of the leading directions for the
      field is the integration of emergency general surgery as a wider and more
      attractive scope of practice. However, there is currently no information on how
      the addition of an emergency general surgery practice will affect the care of
      injured patients. We hypothesized that the care of trauma patients would be
      negatively affected by adding emergency general surgery responsibilities to a
      trauma service. METHODS: Our institution underwent a system change in August
      2001, where an emergency general surgery (ES) practice was added to an
      established trauma service. The ES practice included emergency department and in
      house consultations for all urgent surgical problems except thoracic and vascular
      diseases. There were no trauma staff changes during the study period. Trauma
      registry data (demographics, injuries, injury severity, and procedures) and
      performance improvement data (peer-review judgments for all identified errors,
      denied days, audit filters, and deaths) were abstracted for two 15-month periods
      surrounding this system change. Chi-square, Fisher's exact, and t tests provided
      between-group comparisons. RESULTS: The trauma staff evaluated a total of 5,874
      patients during the 30-month study. There were 1,400 (51%) trauma admissions in
      the pre-ES group and 1,504 (48%) in the post-ES group, of which 1,278 and 1,434,
      respectively, met severity criteria for report to our statewide database
      (Pennsylvania Trauma Outcome Study [PTOS]). There were 163 (12.7% of PTOS) deaths
      in the pre-ES group compared with 171 (11.9% PTOS) deaths in the post-ES group (p
      = not significant [NS]). There was one death determined to be preventable by the
      peer review process for the pre-ES group, and none in the post-ES group. Both
      groups had 10 potentially preventable deaths, with the remaining mortalities
      being categorized as nonpreventable (p = NS). Unexpected deaths by TRISS
      methodology were 36 (2.8%) and 41 (2.9%) for the two groups, respectively (p =
      NS). There was no difference in the number of provider-specific complications
      between the groups (23, [1.8%] vs. 19 [1.3%], p = NS). The addition of emergency
      surgery has resulted in an additional average daily workload of 1.3 cases and 1.2
      admissions. CONCLUSION: Despite an increase in trauma volume over the study
      period, the addition of emergency surgery to a trauma service did not affect the
      care of injured patients. The concept of adding emergency surgery
      responsibilities to trauma surgeons appears to be a valid way to increase
      operative experience without compromising care of the injured patient.

PMID- 15454790
TI  - Blunt renal injuries in children can be managed nonoperatively: outcome in a
      consecutive series of patients.
AB  - BACKGROUND: Nonoperative management of radiographically defined solid organ
      injuries has proven highly successful in children with blunt splenic and hepatic
      injuries. The role of nonoperative management protocols is less well defined for
      blunt renal injuries. The purpose of this study was to review the management and
      outcome of a consecutive series of children with blunt renal injury. METHODS: The
      trauma registry from a Level I pediatric trauma center was reviewed to identify
      all children (age < 19 years) who were treated for a blunt renal injury for the
      period January 1995 through December 2002. Demographic, anatomic, physiologic,
      management, and outcome data were analyzed. RESULTS: For the 8 years of review,
      101 children with a blunt renal injury were identified, including 95 with
      accessible and complete data. The renal injury population had a mean age of 10.4
      years (range, 0.5-18 years) and was 72.6% male. The renal injuries were
      distributed as follows: grade 1, n = 22; grade 2, n = 40; grade 3, n = 20; grade
      4, n = 11; and grade 5, n = 2. Hematuria was present in 88.1% of children (in
      whom urinalysis results were available). Four children had underlying congenital
      renal anomalies. The mean hospital length of stay and intensive care unit stay
      were 6.0 and 2.6 days, respectively. Overall, 5 children (5.3%) required
      laparotomy, including 1 nephrectomy (isolated grade 4 injury) and 1 renorrhaphy,
      for an overall renal salvage rate of 98.9%. In children with isolated renal
      injuries (n = 48), one child (2.1%) required laparotomy. Seven children required
      adjunctive urologic procedures (ureteral stenting, n = 5; cystoscopy/cystogram, n
      = 2). There were seven deaths (7.4% overall; five because of head injury and two
      because of severe abdominal bleeding at presentation). CONCLUSION: A nonoperative
      management strategy was advantageous and successful in pediatric blunt renal
      injuries (94.7% successful nonoperative rate, 98.9% renal salvage rate).
      Adjunctive urologic procedures (e.g., ureteral stenting) were beneficial in
      selected cases.

PMID- 15454791
TI  - A note on the disjointed nature of the injury severity score.
AB  - OBJECTIVE: The Injury Severity Score (ISS) is widely used for anatomic severity
      assessments. The ISS is the sum of the squares of a patient's three worst
      Abbreviated Injury Scale (AIS) severities (1-6) from three specified body
      regions. The set of three AIS severities (including 0s) is called a "triplet."
      ISS values of 9, 17, 18, 25, 26, 27, 29, 33, 34, 41, and 50 can originate from
      two unique triplets, but it is not clear whether the mortalities of the triplets
      are equal. A related question regards the monotonicity of the ISS, that is,
      whether mortality increases with successive values of ISS. This study sought to
      compare the mortality of equivalent ISS values from different triplets and to
      evaluate whether ISS is a monotonic function of mortality. METHODS: The ISS, its
      corresponding three-digit triplet, and the ICISS (an International Classification
      of Diseases, Ninth Revision-based competing score) were calculated for 361,381
      National Trauma Data Bank patients. Fisher's exact tests were used to test for
      mortality differences between triplets that yield the same ISS. Plots of
      mortality by score value were produced to visually assess the monotonicity of the
      ICISS and the ISS. RESULTS: Six of the 11 triplet pairs had mortalities that
      differed by greater than 20%, with the largest difference being 32% for an ISS of
      25 (triplets 0, 0, 5 and 0, 3, 4). Two other values (9 and 17) have triplet pairs
      whose mortality differences are less but still statistically different. The ISS
      is markedly nonmonotonic and is characterized by large spikes in mortality for
      successive ISS values. Plots of the ICISS show it to be largely monotonic.
      CONCLUSION: The ISS is a nonmonotonic, triplet-dependent function of mortality.
      Those who persist in using the ISS to describe populations or make risk
      adjustments should do so cautiously, being sure to account for triplet type.
      These suspect ISS values appear in approximately 25% of cases.

PMID- 15454792
TI  - Computer-assisted communication for critically ill patients: a pilot study.
AB  - BACKGROUND: Critically ill nonverbal patients often have limited means of
      communication through eye-blinking, communication cards, and occasionally
      writing. We evaluated a novel computer communication device to determine its
      clinical utility as an alternative form of communication between patients and
      hospital staff. METHODS: We conducted a prospective pilot study to evaluate a
      communication system (LifeVoice) for intubated nonverbal trauma patients.
      Patients and hospital staff completed questionnaires regarding product
      satisfaction and utility on days 1, 3, and 7. RESULTS: Patients (n = 35) felt the
      system assisted them in obtaining their needs (>90%). Hospital staff (n = 42)
      felt the device improved patient care (96%) and comfort (91%). CONCLUSION: The
      system evaluated offers an effective alternative to traditional means of
      communication in the intensive care unit. Computer-assisted communication
      improves patient comfort and allows advanced patient participation in medical
      care. Further studies will determine whether this modality objectively improves
      patient care by promoting a higher degree of safety and reducing medical errors.

PMID- 15454793
TI  - Reevaluating the management and outcomes of severe blunt liver injury.
AB  - BACKGROUND: The purpose of this study was to identify risk factors that predict
      the need for operative management (OM) of severe blunt liver injury. We also
      sought to determine the impact of interventional angiography (Ang) in the
      treatment and outcomes of these patients. METHODS: Patients with blunt liver
      injuries of grade IV or higher were retrospectively reviewed for their
      demographics, hemodynamics, blood product requirements, laboratory and radiologic
      data, hospital course, and outcomes. RESULTS: Forty-four patients underwent OM.
      They had a significantly higher Injury Severity Score (ISS) and lower Glasgow
      Coma Scale score (p = 0.004), a lower systolic blood pressure (p = 0.002) and a
      higher heart rate (p = 0.02), and higher fluid and transfusion requirements (p <
      0.001) than those treated without OM. Their mortality rate was 66%; 59% of deaths
      were from uncontrolled bleeding. Initial platelet count and fluid requirements at
      4 hours were independent predictors of the need for OM. Ang was performed in 48
      patients. Patients who were treated without Ang required more fluids (p = 0.03)
      and more packed red blood cells (p = 0.02) at 4 hours. Patients requiring both OM
      and Ang had a higher complication rate (p = 0.02) and longer intensive care unit
      and hospital length of stay (p < 0.001) than those who had OM alone, but
      mortality was the same (p = 0.1). Patients treated nonoperatively had longer
      intensive care unit (p = 0.006) and hospital stays (p < 0.05) if they required
      Ang, but mortality was the same. The only survival advantage to the use of Ang
      was when Ang alone was compared with OM alone. CONCLUSION: Select high-grade
      injuries can be successfully managed nonoperatively. Initial platelet count and
      crystalloid fluid use at 4 hours predict the need for OM. Patients requiring OM
      are less stable and have substantial mortality but often do not die as a result
      of uncontrolled bleeding. Ang has a role in stable patients who do not require OM
      initially but does not improve outcome in patients who require OM.

PMID- 15454794
TI  - Evaluating an inclusive trauma system using linked population-based data.
AB  - BACKGROUND: Federal and professional programs require "inclusive" trauma systems.
      We wished to evaluate an inclusive trauma system using administrative data
      combined from multiple sources. METHODS: Ambulance reports, outpatient/inpatient
      discharge data, and/or death certificates were obtained for persons with injury
      diagnoses who received hospital services and/or died in Maine during 1998 to
      2000. Records were unduplicated and joined using probabilistic record-linkage
      software. Case outcomes, determined from one or more linked records, included
      place of hospitalization, discharge status, and 30-day mortality. RESULTS: Per
      100,000 population annually, 11,100 injured persons were treated and released,
      573 were admitted, and 51.3 died. Trauma centers received 37.0% of major cases
      directly and another 15.4% in transfer; 51.4% of injury deaths occurred without
      medical intervention, 21.2% occurred in trauma centers, 20.4% occurred in other
      hospitals, and 7.0% occurred after discharge from a hospital. Database queries
      produced comparative hospital statistics and identification of questionable
      outcomes. CONCLUSION: Record linkage allows inexpensive description of an
      inclusive trauma system and may contribute to quality improvement.

PMID- 15454795
TI  - Cumulative radiation dose caused by radiologic studies in critically ill trauma
      patients.
AB  - BACKGROUND: Critically ill trauma patients undergo many radiologic studies, but
      the cumulative radiation dose is unknown. The purpose of this study was to
      estimate the cumulative effective dose (CED) of radiation resulting from
      radiologic studies in critically ill trauma patients. METHODS: The study group
      was composed of trauma patients at an urban Level I trauma center with surgical
      intensive care unit length of stay (LOS) greater than 30 days. The radiology
      records were reviewed. A typical effective dose per study for each type of plain
      film radiograph, computed tomographic scan, fluoroscopic study, and nuclear
      medicine study was used to calculate CED. RESULTS: Forty-six patients met
      criteria. The mean surgical intensive care unit and hospital LOS were 42.7 +/-
      14.0 and 59.5 +/- 28.5 days, respectively. The mean Injury Severity Score was
      32.2 +/- 15.0. The mean number of studies per patient was 70.1 +/- 29.0 plain
      film radiographs, 7.8 +/- 4.1 computed tomographic scans, 2.5 +/- 2.6
      fluoroscopic studies, and 0.065 +/- 0.33 nuclear medicine study. The mean CED was
      106 +/- 59 mSv per patient (range, 11-289 mSv; median, 104 mSv). Among age,
      mechanism, Injury Severity Score, and LOS, there was no statistically significant
      predictor of high CED. The mean CED in the study group was 30 times higher than
      the average yearly radiation dose from all sources for individuals in the United
      States. The theoretical additional morbidity attributable to radiologic studies
      was 0.78%. CONCLUSION: From a radiobiologic perspective, risk-to-benefit ratios
      of radiologic studies are favorable, given the importance of medical information
      obtained. Current practice patterns regarding use of radiologic studies appear to
      be acceptable.

PMID- 15454796
TI  - Methylene blue enhancement of resuscitation after refractory hemorrhagic shock.
AB  - BACKGROUND: Methylene blue has been used to treat hypovolemic states. This study
      evaluated prehospital resuscitation after refractory hemorrhagic shock with a
      combination of methylene blue and limited-volume lactated Ringer's solution.
      METHODS: After blood loss to a mean arterial pressure of 50 mm Hg in canines,
      refractory hemorrhagic shock was defined as minimal hemodynamic response to
      phenylephrine. Differential protocols included no treatment (control), methylene
      blue bolus, limited-volume lactated Ringer's solution, and combined methylene
      blue/lactated Ringer's solution therapies. Hemodynamic parameters were collected
      at baseline, during shock, during refractory hemorrhagic shock, and 30, 60, 90,
      and 120 minutes after treatment. Radiolabeled microspheres were used to measure
      end-organ perfusion and oxygen delivery. RESULTS: Methylene blue/lactated
      Ringer's resuscitation improved prehospital survival (p < 0.05), mean arterial
      pressure and cardiac output (p < 0.05), vital end-organ blood flow and oxygen
      delivery (p < 0.05), and decreased serum lactate levels (p < 0.05), as compared
      with the methylene blue and lactated Ringer's single therapies. CONCLUSIONS:
      Resuscitation after refractory hemorrhagic shock using a combination of methylene
      blue and limited-volume lactated Ringer's solution improves prehospital survival
      and hemodynamic stability and reduces ischemic damage in an acute setting. This
      form of therapy has been proved useful as a temporizing measure for resuscitation
      after refractory hemorrhagic shock in a canine model and warrants further study
      for its application to the hemorrhagic trauma patient.

PMID- 15454797
TI  - Acute respiratory distress syndrome criteria in trauma patients: why the
      definitions do not work.
AB  - BACKGROUND: The international consensus definitions for acute respiratory
      distress syndrome (ARDS) have formed the basis for recruitment into randomized,
      controlled trials and, more recently, standardized the protocols for ventilatory
      treatment of acute lung injury. Although possibly appropriate for sepsis-induced
      ARDS, these criteria may not be appropriate for posttraumatic ARDS if the disease
      patterns are widely divergent. This study tests the hypothesis that standard ARDS
      criteria applied to the trauma population will capture widely disparate forms of
      acute lung injury and are too nonspecific to identify a population at risk for
      prolonged respiratory failure and associated complications. METHODS: Patients
      with and Injury Severity Score > or = 16 ventilated for > 12 hours were
      prospectively enrolled. Clinical data, including elements of cardiovascular,
      renal, hepatic, hematologic, neurologic, and pulmonary function, were collected
      daily. Two hundred fifty-four patients were enrolled over a 36-month period, of
      whom 70 met the consensus definitions of ARDS. Patients from whom support was
      withdrawn within 48 hours were excluded. The remaining 61 patients were
      stratified into two groups on the basis of intubation (n = 12) days. RESULTS:
      There was considerable disparity in severity and clinical course. A mild, limited
      form of ARDS was characterized by earlier onset (group 1, 2 days; group 2, 4
      days; p = 0.002), fewer intubation days (7 days vs. 28 days; p < 0.001), and less
      severe derangements in lung mechanics. A significant difference between the two
      groups was also seen in systemic inflammatory response syndrome score, incidence
      of sepsis, and incidence of multiple organ failure. CONCLUSION: The criteria for
      ARDS, when applied to the trauma population, capture a widely disparate group and
      has poor specificity for identifying patients at risk. Recruitment of trauma
      patients for ARDS studies or preemptive ventilatory management based solely on
      these criteria may be ill-advised.

PMID- 15454798
TI  - The effects of transforming growth factor-beta neutralization on postburn humoral
      immunity.
AB  - BACKGROUND: Burn injury induces immunosuppression, which is associated with an
      increased susceptibility to infection. Our laboratory has demonstrated that burn
      injury also impairs humoral immunity. We reported that burn injury enhanced
      expression of transforming growth factor-beta (TGF-beta) mRNA and that exogenous
      TGF-beta further impaired humoral immunity. The objective of this study was to
      clarify the role of TGF-beta on humoral immunity after burn injury with a
      neutralizing experiment. METHODS: Twelve BALB/c mice were randomly divided into
      two groups: sham and burn. Anesthetized mice received a 20% full-thickness burn
      or sham injury. The murine splenocytes containing 1.5 x 10 cells/mL were cultured
      with 2.5 microg/mL of lipopolysaccharide with or without 0.5 ng/mL of TGF-beta or
      1 microg/mL of anti-TGF-beta neutralizing antibody, if necessary. Concentrations
      of immunoglobulin (Ig) M in the cell culture supernatant were determined by
      enzyme-linked immunosorbent assay and the number of IgM-secreting cells in the
      culture was measured by enzyme-linked immunospot assay. RESULTS: After 2-day
      culture, neutralization of TGF-beta dramatically restored IgM synthesis after
      burn injury. After 5-day culture, however, it restored IgM concentration but
      failed to restore a number of IgM-secreting cells. CONCLUSION: This neutralizing
      experiment demonstrated that TGF-beta is one of the inhibitors of IgM synthesis
      after burn injury. However, neutralization of TGF-beta was not enough to
      completely restore humoral immunity after burn injury. Investigation of the
      mechanism of impaired IgM synthesis after burn injury should be continued.

PMID- 15454799
TI  - Radiographic characteristics of postinjury splenic autotransplantation: avoiding
      a diagnostic dilemma.
AB  - BACKGROUND: Splenic autotransplantation after postinjury splenectomy has been
      advocated to augment the immune response to infection and prevent overwhelming
      postsplenectomy sepsis. Postoperative computed tomographic (CT) scans in patients
      undergoing splenic autotransplantation reveal multiple intra-abdominal fluid
      collections that may appear similar to abscesses. This presents a diagnostic
      dilemma. In the past, one of our patients underwent percutaneous drainage of such
      collections that were sterile, and one patient required operative evacuation of
      infected implants. The purpose of this study was to determine whether there is a
      characteristic radiographic appearance of splenic implants, whether this
      appearance changes with time, and whether implants can be differentiated from
      abdominal abscesses. STUDY DESIGN: Patients at our Level I trauma center who
      underwent operative therapy for splenic injury from January 1995 to May 2002 were
      identified using our trauma registry. Charts were reviewed and CT scans read in a
      blinded fashion by a radiologist. RESULTS: During the study period, 505 patients
      were admitted for splenic trauma. One hundred forty-five patients (29%) required
      operative intervention for splenic injuries. Splenorrhaphy was performed in 27
      patients and splenectomy was required in 118 patients. Twenty-three patients had
      splenic autotransplantation into the omentum, of whom 11 underwent postoperative
      CT scanning for clinical suspicion of intra-abdominal abscess. On average, 2.7
      scans were obtained per patient, ranging from 4 to 113 days postoperatively.
      Imaging revealed low-density fluid collections in the anterior abdomen in 10 of
      11 patients. Time-related radiographic changes (early rim enhancement and late
      shrinkage) of the implants were noted, but splenic implants lacked surrounding
      omental fat stranding or other inflammatory changes typical of an abscess. The
      patient with infected splenic implants had air bubbles within the fluid
      collections, a characteristic finding of an abscess. CONCLUSION: Autotransplanted
      splenic tissue may resemble an abscess on CT scanning, but splenic implants have
      distinct and time-related characteristic findings. Recognition of these unique
      features may allow differentiation of a splenic implant from an abscess, thus
      avoiding unwarranted intervention.

PMID- 15454800
TI  - High-frequency percussive ventilation: an alternative mode of ventilation for
      head-injured patients with adult respiratory distress syndrome.
AB  - BACKGROUND: Adult respiratory distress syndrome develops in up to 20% of patients
      with severe head injury. This complicates the treatment of head-injured patients
      because lung-protective strategies such as high positive end-expiratory pressure
      (PEEP) and permissive hypercapnia may increase intracranial pressure (ICP) and
      reduce cerebral perfusion pressure. The use of high-frequency percussive
      ventilation (HFPV) is an alternate mode of ventilation that may improve
      oxygenation for head-injured patients while also lowering ICP. METHODS: Clinical
      data were collected retrospectively over a 1-year period. Patients were included
      if they had a severe traumatic brain injury with a Glasgow Coma Score (GCS) of 8
      or lower, a ventriculostomy drain for ICP measurement and cerebral spinal fluid
      drainage, and adult respiratory distress syndrome. Patients were switched from
      conventional mechanical ventilation to HFPV at the discretion of the attending
      trauma surgeon. Data for partial pressure of oxygen to fraction of inspired
      oxygen (PF) ratio, peak inspiratory pressure (PIP), ICP, partial pressure of
      carbon dioxide level (PCO2), PEEP, and mean airway pressure were compared before
      and then 4 and 16 hours after institution of HFPV therapy. RESULTS: A total of 10
      patients met study criteria. Data were expressed as mean +/- standard error.
      There was an increase in PF ratio (91.8 +/- 13.2 vs. 269.7 +/- 34.6; p < 0.01),
      PEEP (14 +/- 2.5 vs. 16 +/- 3.5), and mean airway pressure (20.4 +/- 4.8 vs. 23.6
      +/- 6.8) 16 hours after institution of HFPV. There was a decrease in ICP (30.9 +/
      3.4 vs. 17.4 +/- 1.7; p < 0.01), PC02 (37.7 +/- 4.1 vs. 32.7 +/- 1.1; p < 0.05),
      and PIP (49.4 +/- 10 vs. 41 +/- 7.9; p < 0.05) at 16 hours. Overall mortality was
      10%. CONCLUSIONS: Therapy with HFPV produced a significant improvement in
      oxygenation with a concomitant reduction in ICP during the first 16 hours. This
      therapy may represent an important new method for the management of adult
      respiratory distress syndrome among head-injured trauma patients, although the
      long-term outcome of HFPV still needs evaluation.

PMID- 15454801
TI  - Building a better fluid for emergency resuscitation of traumatic brain injury.
AB  - Hextend (HEX) is a colloid solution that is FDA-approved for volume expansion
      during surgery. ATL-146e is a novel adenosine A2A receptor agonist that has anti
      inflammatory, neuroprotective, and coronary vasodilator properties. Three series
      of experiments were designed to evaluate the therapeutic potential of HEX+/-ATL
      146e for emergency resuscitation from traumatic brain injury (TBI) + hemorrhagic
      hypotension. METHODS: In the first two studies in vivo, anesthetized, ventilated
      pigs (30-45 kg) received a fluid percussion TBI, 45% arterial hemorrhage, and 30
      minutes shock period. In Series 1, resuscitation consisted of unlimited
      crystalloid (n = 8) or HEX (n = 8) to correct systolic arterial pressure >100 mm
      Hg and heart rate <100 bpm for the first 60 minutes ("emergency phase"), and then
      maintain cerebral perfusion pressure (CPP) > 70 mm Hg for 60-240 minutes. In
      Series 2 (n = 31), resuscitation consisted of a 1 L bolus of HEX + ATL-146e (10
      ng/kg/min, n = 10) or HEX +placebo (n = 10) followed by crystalloid to the same
      endpoints. In Series 3 in vivo, the hemodynamic response evoked by 0, 10, 50, or
      100 ng/kg/min ATL-146e was measured before or 60 minutes after HEX resuscitation
      from 45% hemorrhage. RESULTS: Following TBI+hemorrhage, there were 4/22 deaths in
      series 1 and 11/31 deaths in series 2. In those alive at 30 minutes, mean
      arterial pressure, cardiac index, mixed venous O2 saturation, and cerebral venous
      O2 saturation were all reduced by 40-60%, while heart rate and lactate were
      increased 2-5 fold. With no resuscitation (n = 2), there was minimal hemodynamic
      compensation and progressive acidosis. Upon resuscitation, these values corrected
      but intracranial pressure progressively rose from <5 mm Hg to 15-20 mm Hg. Series
      1: With HEX (n = 8) versus crystalloid (n = 8), CPP was less labile, acid/base
      was maintained, and the fluid requirement was reduced by 60% (all p < 0.05)
      Series 2: With ATL-146e (n = 10) versus placebo (n = 10), stroke volume and
      cardiac output were improved by 40-60%, and the fluid requirement was reduced by
      30% (all p < 0.05). Series 3: ATL-146e caused a dose-related increase (p < 0.05)
      in stroke volume after, but not before, hemorrhage. The effects on pre-load,
      afterload, and heart rate were similar before and after hemorrhage. CONCLUSIONS:
      HEX alone is a safe and efficacious low volume alternative to initial crystalloid
      resuscitation after TBI. An adenosine A2A agonist combined with 1 L of HEX safely
      and effectively counteracted a decrease in cardiac performance noted after
      TBI+hemorrhage without causing hypotension or bradycardia.

PMID- 15454802
TI  - Application of a granular mineral-based hemostatic agent (QuikClot) to reduce
      blood loss after grade V liver injury in swine.
AB  - BACKGROUND: Uncontrolled hemorrhage is a leading cause of death in cases of
      trauma. Many products currently are under development to control traumatic
      bleeding. One such Food and Drug Administration (FDA)-approved product is
      QuikClot. This study determined the efficacy of QuikClot, a hemostatic agent, in
      reducing blood loss and mortality in a standardized model of severe liver injury
      as well as the consequences of its use. METHODS: Swine received either QuikClot
      or gauze treatment after induction of grade V liver injuries. Hemostasis, blood
      loss, resuscitation volume, 60-minute survival, and peak tissue temperatures were
      measured. RESULTS: Hemostasis was improved with QuikClot (p < 0.05), and
      resuscitation volume was consequently reduced (p < 0.05). Posttreatment blood
      loss was reduced (p < 0.01) with QuikClot (1,397 mL), as compared with gauze
      (5,338 mL). The survival rate was seven of eight in the QuikClot group and one of
      eight in the gauze group (p < 0.01). Peak temperature at the tissue interface was
      increased (p < 0.01) with QuikClot (93.3 +/- 10.5 degrees C), as compared with
      gauze (37.5 +/- 6.5 degrees C). QuikClot use was associated with both macro- and
      microscopic tissue damage caused by the exothermic reaction. CONCLUSION: QuikClot
      provides hemostasis and decreased mortality in this model of severe liver injury.
      The beneficial aspects of QuikClot treatment must, however, be balanced against
      the tissue-damaging effects of the exothermic reaction.

PMID- 15454803
TI  - Is a restrictive transfusion strategy safe for resuscitated and critically ill
      trauma patients?
AB  - BACKGROUND: An analysis from the prospective multicenter randomized controlled
      trial (Transfusion Requirements in Critical Care Trial) compared the use of
      restrictive and liberal transfusion strategies with resuscitated critically ill
      trauma patients. METHODS: Critically ill trauma patients with a hemoglobin
      concentration less than 90 g/L within 72 hours of admission to the intensive care
      unit were randomized to a restrictive (hemoglobin concentration, 70 g/L) or
      liberal (hemoglobin concentration, 100 g/L) red blood cell transfusion strategy.
      RESULTS: The baseline characteristics in the restrictive (n = 100) and liberal (n
      = 103) transfusion groups were comparable. The average hemoglobin concentrations
      (82.7 +/- 6.2 g/L vs. 104.3 +/- 12.2 g/L; p < 0.0001) and the red blood cell
      units transfused per patient (2.3 +/- 4.4 vs. 5.4 +/- 4.3; p < 0.0001) were
      significantly lower in the restrictive group than in the liberal group. The 30
      day all-cause mortality rates in the restrictive group were 10%, as compared with
      9% in the liberal group (p = 0.81). The presence of multiple organ dysfunction
      (9.2 +/- 6.3 vs. 9.0 +/- 6.0; p = 0.81), the changes in multiple organ
      dysfunction from baseline scores adjusted for death (1.2 +/- 6.1 vs. 1.9 +/- 5.7;
      p = 0.44), and the length of stay in the intensive care unit (9.8 +/- 8.1 vs.
      10.2 +/- 8.7 days; p = 0.73) and hospital (31.4 +/- 17.1 vs. 33.7 +/- 17.7 days;
      p = 0.34) also were similar between the restrictive and liberal transfusion
      groups. CONCLUSIONS: A restrictive red blood cell transfusion strategy appears to
      be safe for critically ill multiple-trauma patients. A randomized controlled
      trial would provide the appropriate level of evidence with regard to the daily
      use of blood in this population of patients.

PMID- 15454804
TI  - Increased susceptibility to oxidant injury in hepatocytes from rats with intra
      abdominal hypertension.
AB  - BACKGROUND: Intra-abdominal hypertension leads to visceral organ hypoperfusion,
      and subsequent decompression may cause ischemia-reperfusion, releasing toxic
      metabolites. This study focuses on the effect of intra-abdominal hypertension on
      hepatic antioxidant store and the susceptibility of hepatocytes to oxidant
      injury. METHODS: Sprague-Dawley rats (150-180 g) were acclimatized to an
      environment for 3 days and then divided into two groups according to challenge
      based on intra-abdominal pressure (0 and 30 cm H2O for control and experimental
      groups, respectively). After a 90-minute challenge, the rats underwent immediate
      laparotomy for decompression; after a further 30 minutes, one fragment of liver
      from the lingual lobe (>0.1 g) was excised to measure glutathione (GSH) in vivo
      before portal vein perfusion. After hepatocyte isolation (viability rate > 85%),
      the cell density was set at 1 x 10/mL for each well. The samples were cultured in
      an incubator for 12 hours, after which varying concentrations of t-butyl
      hydroperoxide (TBHP) (0.0, 0.5, 1.0, and 2.0 mmol/L) were added into the wells.
      After another 5-hour incubation, the total store of intracellular GSH in vitro
      (GSHVT) and the hepatocyte survival rates were measured for different groups of
      TBHP challenge using GSH assay and MTT kits. RESULTS: The control and
      experimental groups consisted of 10 and 8 rats, respectively, that successfully
      completed the entire experimental procedure. Compared with the control group, the
      in vivo GSH store was significantly reduced after the intra-abdominal pressure
      challenge (mean +/- SE, 968.1 +/- 63.5 vs. 1,581.0 +/- 115.3 nmol/g of protein; p
      = 0.001). After the hepatocyte isolation, the GSHVT stores at various TBHP
      concentrations in the experimental rats were also similarly and significantly
      decreased relative to the control animals (894.4 +/- 56.4, 804.2 +/- 118.4, 586.9
      +/- 86.6, and 410.2 +/- 87.4 nmol/g of protein vs. 1,282.2 +/- 112.0, 1,156.6 +/-
      91.0, 995.2 +/- 92.7, and 866.8 +/- 62.4 nmol/g of protein for TBHPs of 0.0, 0.5,
      1.0, and 2.0 mmol/L, respectively; all p < 0.05). Moreover, from photocytometry,
      the hepatocyte survival rates were significantly reduced for the experimental
      rats compared with the control animals after challenge with various TBHP
      concentrations (survival was 100%, 91.1%, 81.3%, and 72.8% vs. 100%, 99.2%,
      95.0%, and 88.2%, respectively, for TBHPs of 0.0, 0.5, 1.0, and 2.0 mmol/L; p <
      0.05 for the last two). CONCLUSION: This animal study demonstrated that intra
      abdominal hypertension and subsequent decompression deplete the total in vivo GSH
      store in rat livers, probably via the mechanism of ischemia-reperfusion injury,
      and the GSHVT after hepatocyte isolation, which makes the isolated hepatocytes of
      rats more susceptible to oxidant challenge.

PMID- 15454805
TI  - Profile of chest trauma in a level I trauma center.
AB  - BACKGROUND: Chest injuries are seen with increasing frequency in urban hospitals.
      The profile of chest injuries depends on the size of the hospital and the level
      of trauma center. The data regarding the true incidence of chest trauma are
      scant. METHODS: One thousand three hundred fifty-nine consecutive patients seen
      at a Level I trauma center were analyzed. The nature of injury, methods of
      treatment, and morbidity and mortality were recorded in a prospective manner and
      analyzed retrospectively. Multiple logistic regression analysis was used to
      determine the independent predictors of mortality after chest trauma. RESULTS:
      The overall mortality was 9.41%. Low Glasgow Coma Scale score, older age,
      presence of penetrating chest injury, long bone fractures, fracture of more than
      five ribs, and liver and spleen injuries were independent predictors of death
      after chest trauma. A model was created for predicting the mortality based on
      various factors. CONCLUSION: Most chest injuries can be treated with simple
      observation. Only 18.32% of patients required tube thoracostomy and 2.6% needed
      thoracotomy. Low Glasgow Coma Scale score and advanced age are the most
      significant independent predictors of mortality.

PMID- 15454806
TI  - Thoracic aortic injury in motor vehicle crashes: the effect of impact direction,
      side of body struck, and seat belt use.
AB  - BACKGROUND: Using in-depth, real-world motor vehicle crash data from the United
      States and the United Kingdom, we aimed to assess the incidence and risk factors
      associated with thoracic aorta injuries. METHODS: De-identified National
      Automotive Sampling System Crashworthiness Data System (U.S.) and Co-operative
      Crash Injury Study (U.K.) data formed the basis of this retrospective analysis.
      Logistic regression was used to assess the level of risk of thoracic aorta injury
      associated with impact direction, seat belt use and, given the asymmetry of the
      thoracic cavity, whether being struck toward the left side of the body was
      associated with increased risk in side-impact crashes. RESULTS: A total of 13,436
      U.S. and 3,756 U.K. drivers and front seat passengers were analyzed. The
      incidence of thoracic aorta injury in the U.S. and U.K. samples was 1.5% (n =
      197) and 1.9% (n = 70), respectively. The risk was higher for occupants seated on
      the side closest to the impact than for occupants involved in frontal impact
      crashes. This was the case irrespective of whether the force was applied toward
      the left (belted: relative risk [RR], 4.6; 95% confidence interval [CI], 2.9-7.1;
      p < 0.001) or the right side (belted: RR, 2.6; 95% CI, 1.4-5.1; p < 0.004) of the
      occupant's body. For occupants involved in side-impact crashes, there was no
      difference in the risk of thoracic aorta injury whether the impacting force was
      applied toward the left or toward the right side of the occupant's body. Seat
      belt use provided a protective benefit such that the risk of thoracic aorta
      injury among unbelted occupants was three times higher than among belted
      occupants (RR, 3.0; 95% CI, 2.2-4.3; p < 0.001); however, the benefit varied
      across impact direction. Thoracic aorta injuries were found to be associated with
      high impact severity, and being struck by a sports utility vehicle relative to a
      passenger vehicle (RR, 1.7; 95% CI, 1.2-2.3; p = 0.001). CONCLUSION: Aortic
      injuries have been conventionally associated with frontal impacts. However,
      emergency clinicians should be aware that occupants of side-impact crashes are at
      greater risk, particularly if the occupant was unbelted and involved in a crash
      of high impact severity.

PMID- 15454807
TI  - Street bikes versus dirt bikes: a comparison of injuries among motorcyclists
      presenting to a regional trauma center.
AB  - BACKGROUND: This study sought to compare the spectrum of injuries and outcomes
      between off-road and on-road motorcyclists. METHODS: Demographic information,
      accident location, helmet use, anatomic injuries, physiologic data, length of
      stay, transfusions, operations, Injury Severity Scores, and determination of
      death were abstracted for a consecutive cohort of patients over a 5-year period.
      RESULTS: There were no significant differences between off-road motorcyclists (n
      = 376) and on-road motorcyclists (n = 371) in terms of helmet use, loss of
      consciousness, initial systolic blood pressure, initial Glasgow Coma Scale,
      initial Revised Trauma Score, or hand, wrist, forearm, arm, clavicle, foot,
      ankle, femur, pelvis, spinal, or head injuries. On-road motorcyclists were
      significantly more likely, however, to require transfusions (p < 0.025); sustain
      blunt chest, abdominal, or skin trauma; or die (p < 0.05). CONCLUSIONS: On-road
      motorcyclists are more likely to sustain blunt abdominal trauma, blunt chest
      trauma, skin trauma, and death than off-road motorcyclists.

PMID- 15454808
TI  - Clinical and functional results after floating shoulder injuries.
AB  - BACKGROUND: Good results have been reported with both operative and nonoperative
      treatment of floating shoulder, and discussions about an appropriate therapy of
      this rare entity are controversial because of small numbers of patients. METHODS:
      Seventeen patients with a floating shoulder were retrospectively evaluated. The
      treatment was nonoperative in eight patients and operative in nine. All patients
      were clinically examined and standard shoulder radiographs were obtained at the
      time of follow-up. RESULTS: All fractures healed. Five patients in the
      nonoperative and five patients in the operative group showed good to excellent
      results. The associated injuries influence the outcome of these patients
      significantly. CONCLUSION: Nondisplaced or less displaced floating shoulders are
      expected to give good results after nonoperative treatment. If mostly heavy
      associated injuries allow it, significantly displaced fractures should be treated
      operatively.

PMID- 15454809
TI  - Acute shortening: modular treatment modality for severe combined bone and soft
      tissue loss of the extremities.
AB  - BACKGROUND: Acute shortening, using the Ilizarov technique followed by
      progressive lengthening, is one of the methods used to deal with complex
      fractures combined with severe soft tissue injuries. METHODS: We have summarized
      12 patients who underwent acute shortening and stabilization using the Ilizarov
      frame. Nine of them underwent progressive lengthening to restore the length. For
      three patients, angulation of the bone segments was performed to save them from
      excessive bone debridement. RESULTS: Total wound closure and bone regeneration
      were achieved in all our patients. Five patients had pin-tract infection without
      involvement of the bone, and no major complications were noted. CONCLUSION: Using
      this technique, we found some advantages. First, there is less need for free and
      local flaps. Second, there is a decrease in the operating time and donor-site
      morbidity (important for patients with multiple organ trauma). Third, it provides
      a good option for restoring defects in severe cases with combined bone and soft
      tissue defects in the same session. Fourth, its implementation for short bone
      defects (< 3 cm) gives acceptable aesthetic and functional results. Fifth,
      angulation of the segments and subsequent graduated correction of misalignment
      reduces the length of shortening needed in patients with severe soft tissue loss
      by sparing the bone from unnecessary debridement. Sixth, it permits definitive
      treatment using an external fixator device, enabling the possibility of early
      functional loading. On the basis of our experience, we suggest adopting this
      method for functional limb salvage after extensive complex high-energy injuries.

PMID- 15454810
TI  - Motion generated in the unstable spine during hospital bed transfers.
AB  - BACKGROUND: The purpose of this study was to compare the motion generated when
      executing the bed transfer procedure in cadavers with unstable lower cervical
      spines. METHODS: Five cadavers received a global instability at the C5-6 level.
      Each cadaver was moved with and without a rigid cervical collar. The amount of
      translation resulting from the bed transfer was measured. RESULTS: Statistical
      analysis revealed no difference in spinal movement between treatments (with or
      without a collar). Anterior/posterior (AP) and medial/lateral motions were
      similar in magnitude and much higher than longitudinal motion. CONCLUSIONS: There
      was very little resistance to motion in the AP and lateral directions. Thus, it
      may not be surprising that no difference in the amount of motion was noted
      between transfers conducted by skilled hands with or without a collar. Current
      hospital transfer techniques have the potential to inflict an unacceptably large
      displacement on an unstable spine.

PMID- 15454811
TI  - Influence of the incompletely erupted lower third molar on mandibular angle and
      condylar fractures.
AB  - BACKGROUND: Several studies have shown an increased risk of mandibular angle
      fractures by the presence of the lower third molar (M3), especially the
      incompletely erupted M3. The presence of M3s might influence condylar fractures,
      which is one of the most common fracture sites, as well as the angle fracture.
      METHODS: Six hundred ninety-two mandibular sides among 346 patients with
      mandibular fracture were analyzed. They were classified into two groups according
      to the presence of incompletely erupted M3s and were analyzed according to
      fracture site, age, and cause of injury. RESULTS: Among these patients with
      mandibular fractures, the frequency of occurrence of the mandibular angle
      fracture was higher in the group with incompletely erupted M3s (p < 0.0001) and
      that of the condylar fracture was higher in the group without it (p < 0.001).
      CONCLUSION: The result of this retrospective investigation shows that an
      incompletely erupted M3 decreases the risk of condylar fractures and increases
      the risk of mandibular angle fractures.

PMID- 15454812
TI  - Granulocyte colony-stimulating factor has differing effects comparing
      intravascular versus extravascular models of sepsis.
AB  - BACKGROUND: Previously, neutrophil stimulation with granulocyte colony
      stimulating factor (G-CSF) pretreatment increased survival rates in canines
      challenged with intraperitoneal or intrabronchial Escherichia coli and in rats
      challenged with intrabronchial Staphylococcus aureus. We investigated whether G
      CSF pretreatment would be beneficial with intravascular challenge in these
      models. METHODS: Animals were randomized to G-CSF or placebo pretreatment
      followed by intravenous E. coli challenge in canines (n = 24) or intravenous or
      intrabronchial S. aureus challenge in rats (n = 273). All animals were treated
      with antibiotics. RESULTS: In canines, G-CSF before intravenous E. coli did not
      decrease mortality rates (7 of 12 [58%] G-CSF vs. 5 of 12 [42%] controls), which
      contrasted with prior reductions during extravascular infection (10 of 35 [29%] G
      CSF vs. 37 of 65 [57%] controls). Consistent with the present and previously
      published studies in canines, in rats, G-CSF decreased mortality rates with
      intrabronchial S. aureus (22 of 90 [24%] G-CSF vs. 26 of 51 [51%] controls, p =
      0.009) but did not decrease them with intravenous infection (34 of 67 [50%] G-CSF
      vs. 27 of 65 [42%] controls, p = 0.2) in patterns that were very different (p =
      0.005 for the effects of G-CSF with intravascular vs. intrabronchial S. aureus).
      CONCLUSION: In contrast to extravascular infection, sepsis with intravascular E.
      coli in canines and S. aureus in rats may not provide a compartmentalized nidus
      of bacteria on which G-CSF-stimulated neutrophils can exert a beneficial
      antimicrobial effect. Extrapolated clinically, a proinflammatory agent like G-CSF
      may be most beneficial with sepsis related primarily to a compartmentalized
      extravascular site of infection.

PMID- 15454813
TI  - Firearms and suicide in the northeast.
AB  - BACKGROUND: A central question in suicide research is whether firearm
      availability increases the overall number of suicides rather than the proportion
      of suicides from guns. METHODS: Seven state health departments supplied mortality
      and hospital discharge data for all suicides and nonfatal hospitalized suicide
      attempts between 1996 and 2000. Firearm prevalence measures came from the
      Behavioral Risk Factor Survey Surveillance. Pearson correlation coefficients and
      associated chi statistics were used to quantify the relation between firearm
      prevalence and rates of suicide; ordinary least squares regression was used to
      explore whether the relation could be explained by differences across states in
      attempt rates or method-specific case fatality rates. RESULTS: Firearm prevalence
      was positively related to the suicide rate, even after controlling for rates of
      attempted suicide, and could not be accounted for by differences in method
      specific case fatality rates. CONCLUSION: When it comes to suicide, the
      availability of household firearms matters-a lot.

PMID- 15454814
TI  - Massive haemorrhage from hepatic laceration with diaphragmatic laceration: a
      potential limitation of the FAST examination: case report.
AB  - This report describes the case of a multitrauma patient who had life-threatening
      intraabdominal hemorrhage with a diaphragmatic laceration. This hemorrhage
      remained undetected by serial focus assessment with sonography for trauma (FAST)
      examination. The potential for intraabdominal blood to move through a
      diaphragmatic laceration to the pleural space may limit the development of
      hemoperitoneum, rendering the FAST examination misleading or producing a false
      negative result. The use of the FAST examination is discussed along with its
      advantages and limitations.

PMID- 15454815
TI  - Blunt cardiac rupture in a patient with prior ventricular septal defect repair: a
      case report.

PMID- 15454816
TI  - Endovascular repair of blunt abdominal aortic injury: case report.

PMID- 15454817
TI  - Methemoglobinemia in a trauma patient.

PMID- 15454818
TI  - Luxatio erecta associated with a surgical neck fracture of the humerus.

PMID- 15454819
TI  - Simultaneous bilateral lower leg replantation: evaluation by different scoring
      systems--a critical analysis.

PMID- 15454820
TI  - Transoral crossbow injury: an unusual case of central nervous system foreign
      body.

PMID- 15454821
TI  - Surgical education and the residency program in Finland.

PMID- 15454822
TI  - Practice management guidelines for nutritional support of the trauma patient.

PMID- 15454823
TI  - Foreign body in the tracheobronchial tree as a complication of facial injury.

PMID- 15454824
TI  - Evidence that albumin is protective in shock.

PMID- 15454826
TI  - Surgeon-performed ultrasound for pneumothorax in the trauma suite.

PMID- 15454827
TI  - Seat belt use during pregnancy.

PMID- 15454828
TI  - Surgeon-performed thoracic sonography for ruling out pneumothorax.

PMID- 15454830
TI  - Cancer occurrence in Southeast Asian children in California.
AB  - OBJECTIVES: To estimate misclassification of ethnicity and cancer incidence in
      Southeast Asian children using the population-based California Cancer Registry.
      METHODS: Asian race/ethnicity was evaluated using lists of Asian surnames.
      Average annual incidence rates (per million) for 1988 to 1992 were calculated for
      non-Hispanic white, black, Hispanic, and Asian children (age <15 years).
      Proportional incidence ratios (PIRs) for 1988 to 1995 were used to compare
      Southeast Asian children to non-Hispanic white children. RESULTS: Of the Asian
      children, 4.2% (30/722) were misclassified by subgroup, predominantly Hmong
      listed as Laotian. The Asian cancer rate was 134.2 versus 159.2 for non-Hispanic
      whites. The germ cell tumor rate was higher in Asians (9.9) than in non-Hispanic
      whites (4.8), but the Wilms tumor rate was two-thirds lower (3.1 vs. 9.2). The
      rates of Hodgkin lymphoma and central nervous system tumors were lower (2.8 vs.
      5.6 and 20.0 vs. 33.8) in Asians than non-Hispanic whites. Compared with non
      Hispanic whites, the PIR for Wilms tumor in Southeast Asian children was reduced
      (PIR = 0.1). Southeast Asian children had increased PIRs for Burkitt lymphoma
      (PIR = 2.6) and leukemias not classified as acute lymphocytic leukemia or acute
      nonlymphocytic leukemia (PIR = 3.5). CONCLUSIONS: Accurate race/ethnicity
      classification of Southeast Asian children is a concern. Marked differences were
      found in the incidence and PIRs of specific cancers among Southeast Asian
      children, other Asian children, and other children in California.

PMID- 15454831
TI  - Oral glutamine supplementation decreases resting energy expenditure in children
      and adolescents with sickle cell anemia.
AB  - OBJECTIVES: To determine the effects of orally administered glutamine on the
      resting energy expenditure (REE) and nutritional status of children and
      adolescents with sickle cell anemia. METHODS: Twenty-seven children and
      adolescents (13 boys, 14 girls), 5.2 to 17.9 years old (median 11.0 years),
      received orally administered glutamine (600 mg/kg per day) for 24 weeks. Measures
      of REE and other nutritional parameters were compared at baseline and 24 weeks.
      RESULTS: After 24 weeks, the patients' median REE (kcal/d) decreased by 6% (P =
      0.053) as indicated by the Harris Benedict equations and by 5% (P = 0.049) as
      indicated by the modified equations. Patients with less than 90% ideal body
      weight had even greater declines in REE after 24 weeks (P < 0.03 and 0.02,
      respectively). Improvements in nutrition parameters and in two amino acids in the
      plasma were observed. CONCLUSIONS: After 24 weeks of orally administered
      glutamine, children and adolescents with sickle cell anemia had a decrease in REE
      and improvement in nutritional parameters. Those who were underweight had a
      greater decrease in REE than those of normal body weight. Lowering REE may be an
      effective way to improve the growth of these children and adolescents.

PMID- 15454832
TI  - Transcranial Doppler changes in children with sickle cell disease on transfusion
      therapy.
AB  - Transcranial Doppler (TCD) is an effective method for screening patients with
      sickle cell disease (SCD) at risk for first stroke. Its usefulness in monitoring
      children with SCD receiving transfusions has not been established. The authors
      studied 17 children with SCD evaluated with TCDs and magnetic resonance
      angiograms (MRAs) while receiving transfusion therapy. Patients with normalized
      TCDs had normal MRAs that remained normal on transfusions. Patients with
      persistently abnormal TCDs had abnormal MRAs. In these children, TCD velocities
      decreased but rarely reverted to normal. Patients with low TCD velocities (<70
      cm/s) had corresponding vasculopathy on MRA. Low velocities may be a risk factor
      for stroke and should be followed. Overall, there was good correlation between
      TCD velocity changes and MRA analysis.

PMID- 15454833
TI  - Fermented wheat germ extract reduces chemotherapy-induced febrile neutropenia in
      pediatric cancer patients.
AB  - PURPOSE: An open-label, matched-pair (by diagnosis, stage of disease, age, and
      gender) pilot clinical trial was conducted to test whether the combined
      administration of the medical nutriment MSC (Avemar) with cytotoxic drugs and the
      continued administration of MSC on its own help to reduce the incidence of
      treatment-related febrile neutropenia in children with solid cancers compared
      with the same treatments without MSC. METHODS: Between December 1998 and May
      2002, 22 patients (11 pairs) were enrolled in this study. At baseline, the
      staging of the tumors was the same in each pair (mostly pTNM = T2N0M0), with the
      exception of two cases in which patients in the MSC group had worse prognoses
      (metastasis at baseline). There were no significant differences in the average
      age of the patients, the length of treatment time (MSC) or follow-up, the number
      of patients with central venous catheters, the number of chemotherapy cycles, the
      frequency of preventive counterneutropenic interventions, or the type and dosage
      of antibiotic and antipyretic therapy used in the two groups. RESULTS: During the
      treatment (follow-up) period, there was no progression of the malignant disease,
      whereas at end-point the number and frequency of febrile neutropenic events
      significantly differed between the two groups: 30 febrile neutropenic episodes
      (24.8%) in the MSC group versus 46 (43.4%) in the control group (Wilcoxon signed
      rank test, P < 0.05). CONCLUSIONS: The continuous supplementation of anticancer
      therapies with the medical nutriment MSC helps to reduce the incidence of
      treatment-related febrile neutropenia in children with solid cancers.

PMID- 15454834
TI  - Viral infections in juvenile myelomonocytic leukemia: prevalence and clinical
      implications.
AB  - OBJECTIVES: Viral infections may complicate the diagnosis of juvenile
      myelomonocytic leukemia (JMML) in a substantial proportion of patients, but this
      possibility has not been tested in a prospective study. The authors therefore
      measured the cellular expression of the MxA protein, a reliable marker of viral
      infection, at diagnosis in children with JMML to estimate the prevalence of such
      infections. METHODS: Eighteen children, aged 1 to 69 months, who met the
      diagnostic criteria of the International JMML Working Group were prospectively
      studied. MxA expression was assessed by flow cytometric analysis of peripheral
      blood mononuclear cells stained with an antihuman MxA antibody. All data were
      obtained through the MDS Committee of the Japanese Society of Pediatric
      Hematology. RESULTS: Twelve patients (67%) had elevated levels of the MxA
      protein, with rotavirus, RS virus, or CMV infection documented in three of these
      patients. Although none of the patients had primary Epstein-Barr virus (EBV)
      infection, reactivation of the virus was strongly suspected in four children,
      including two with monosomy 7, each having increased levels of MxA. Southern blot
      analysis revealed monoclonal integration of the EBV genome into bone marrow
      mononuclear cells from one of these patients. There was no discernible
      correlation between increases in the marker protein and the presenting features
      or course of the disease. CONCLUSIONS: Viral infection may be present in two
      thirds of children with newly diagnosed JMML, but it does not constitute a basis
      for revising clinical management. The possibility that EBV or other viruses
      contribute to JMML pathogenesis by stimulating pre-exiting malignant clones
      warrants further investigation.

PMID- 15454835
TI  - Emotional, social, and behavioral functioning of children with sickle cell
      disease and comparison peers.
AB  - This research examined the emotional, social, and behavioral functioning of
      children with sickle cell disease (SCD) and classroom comparison peers from the
      perspective of primary and secondary caregivers. It was hypothesized that
      children with SCD would have more internalizing (emotional) and social problems
      and fewer externalizing (behavioral) problems than comparison peers. Caregivers
      of 70 children with SCD and 67 comparison peers completed the Child Behavior
      Checklist (CBCL) during visits to the children's homes. Relative to comparison
      peers, children with SCD were perceived by primary caregivers as having more
      total and internalizing problems and less total competence. Additionally,
      significantly more children with SCD exceeded clinical cutoffs on the CBCL. While
      caregivers of children with SCD perceive these children to be at a slightly
      elevated risk for problems across multiple domains, a significant number of
      children with SCD have problems in the clinical range. The authors recommend that
      vigorous screening programs for mental health problems should be included in the
      routine care of children with SCD, and programs of psychosocial intervention
      research should be implemented to ameliorate problems for the children at
      greatest risk.

PMID- 15454836
TI  - Platinum compound-related ototoxicity in children: long-term follow-up reveals
      continuous worsening of hearing loss.
AB  - OBJECTIVES: The purpose of this study was to evaluate the severity of hearing
      loss after cisplatin and/or carboplatin treatment in young children and to
      analyze its evolution and its relation to different therapy schedules. METHODS:
      One hundred twenty patients treated in the Pediatrics Department at the Institut
      Gustave-Roussy from 1987 to 1997 for neuroblastoma, osteosarcoma, hepatoblastoma,
      or germ cell tumors were analyzed. Median age at diagnosis was 2.6 (range 0-17)
      years. Median follow-up was 7 (1-13) years. Chemotherapy regimens contained
      cisplatin and/or carboplatin. Three patients also received high-dose carboplatin.
      Cisplatin was administered at a dose of 200 mg/m/course in 72% of cases. The
      median cumulative dose was 400 mg/m for cisplatin and 1,600 mg/m for carboplatin.
      Hearing loss of grade 2 or above, according to Brock's grading scale, was
      revealed with pure tone audiometry and behavioral techniques. RESULTS:
      Carboplatin alone was not ototoxic. Deterioration of hearing of grade 2 or above
      was observed in 37% of patients treated with cisplatin and 43% of patients
      treated with cisplatin plus carboplatin (P = NS). Fifteen percent of patients
      experienced grade 3 or 4 ototoxicity. Ototoxicity was most often observed after a
      total cisplatin dose of at least 400 mg/m. No improvement was observed with time;
      on the contrary, worsening or progression of hearing loss at lower frequencies
      was detected during follow-up. Only 5% of audiograms showed toxicity of at least
      grade 2 before the end of therapy; in contrast, this level was observed in 11% of
      early post-therapy evaluations and in 44% after more than 2 years of follow-up.
      CONCLUSIONS: Children treated with cisplatin at cumulative doses approaching 400
      mg/m require long-term surveillance to avoid overlooking hearing deficits.
      Carboplatin, at a standard dose, does not appear to be a significant risk factor
      for ototoxicity even in patients who have already been treated with cisplatin.

PMID- 15454837
TI  - X-linked chronic granulomatous disease: first report of mutations in patients of
      Argentina.
AB  - BACKGROUND: Chronic granulomatous disease (CGD) is a primary immunodeficiency due
      to absent or decreased NADPH oxidase activity in phagocytic cells. The X-linked
      form of the disease (X-CGD) arises from mutations in the CYBB gene, which encodes
      the 91-kD glycoprotein gp91(phox), the largest component of the oxidase. METHODS:
      The authors recently started the molecular characterization of X-CGD in 18
      patients reported to the Argentinean Registry of Primary Immunodeficiency
      Diseases. The authors reviewed data from clinical records to examine the
      relationship of clinical presentation and the type of mutations responsible for
      the genotype. RESULTS: The frequency and type of infections present in these
      patients were similar to prior reports. However, pulmonary tuberculosis was
      observed in the group as well as unusual complications such as eosinophilic
      cystitis, hepatic abscess with cholangitis, and chronic orchitis. Eleven
      different mutations in the CYBB gene were identified, and seven of them were
      novel. The types of mutations were intronic, single-nucleotide substitution
      resulting in nonsense or missense codons and one or two nucleotide deletions
      resulting in frameshifts. Molecular studies of 18 mothers revealed X-CGD carrier
      status in all but 2. CONCLUSIONS: No correlation existed between the type of
      mutation and the clinical phenotype of the disease: the molecular defects
      identified resulted in no expression of the flavocytochrome b558 in patients'
      neutrophils, leading to the X91(o)-CGD phenotype. The lack of gp91(phox) protein
      could explain the early onset and the severity of the clinical manifestations of
      CGD in this group of patients from Argentina.

PMID- 15454838
TI  - Pharmacokinetics of rofecoxib in children with sickle cell hemoglobinopathy.
AB  - Rofecoxib is a selective cyclooxygenase-2 (COX-2) inhibitor approved for the
      treatment of pain and arthritis in adults. It is available as a suspension, but
      there are no published pediatric pharmacokinetic data. This study characterized
      the disposition of rofecoxib in children with sickle cell hemoglobinopathy in a
      single-oral-dose, intensive pharmacokinetic study. Eight subjects aged 3 to 14
      years (mean 8.9 years, 5 boys and 3 girls) received a single oral dose of
      rofecoxib (1 mg/kg, maximum 50 mg) as a suspension. Blood samples were collected
      over 72 hours following drug administration and plasma was assayed for rofecoxib
      using high-performance liquid chromatography (HPLC). Pharmacokinetic parameters
      (peak concentration [Cmax], time to reach peak concentration [tmax], area under
      the curve [AUC], oral clearance [Cl/F], elimination half-life [t1/2]) were
      calculated using standard noncompartmental methods. The mean dose was 35.6 mg
      (range 15-50 mg). Cmax averaged 582 +/- 129 ng/mL, with a median tmax of 4.0
      hours. Secondary peaks were observed in two subjects. Two subjects were
      discharged at 12 hours, preventing characterization of elimination. In the
      remaining six subjects, Cl/F averaged 1.34 +/- 0.32 mL/min/kg, with a t1/2 of
      14.8 +/- 4.5 hours. No significant adverse events were observed. The disposition
      of rofecoxib in children appears to be similar to that in adults, with comparable
      values for Cmax, tmax, t1/2, and Cl/F.

PMID- 15454839
TI  - Hyperexcitable blink reflex preceding the diagnosis of neuroblastoma.
AB  - The diagnosis of neuroblastoma is sometimes preceded by development of a
      paraneoplastic syndrome, most commonly opsoclonus-myoclonus-ataxia (OMA). The
      authors describe a patient who developed a hyperexcitable blink reflex, without
      symptoms of OMA, prior to his oncologic diagnosis. The authors believe this may
      represent a distinct paraneoplastic process caused by increased dopaminergic
      stimulation of the blink reflex and suggest that children manifesting an
      unexplained hyperexcitable blink reflex should be screened for occult
      neuroblastoma.

PMID- 15454840
TI  - Nonketotic hyperosmolar coma associated with splenic rupture in congenital
      afibrinogenemia.
AB  - Nonketotic hyperosmolar coma is uncommon in children. Splenic rupture in
      congenital afibrinogenemia is also a rare event. The authors described a 5-year
      old girl with congenital afibrinogenemia who presented with nonketotic
      hyperosmolar coma associated with spontaneous splenic rupture. Management
      consisted of correction of the nonketotic hyperosmolar condition and increasing
      fibrinogen concentration by blood products, followed by splenectomy, resulting in
      the survival of the patient.

PMID- 15454841
TI  - Lymphoblastic leukemia with mature B-cell phenotype in infancy.
AB  - Lymphoblastic leukemias with surface immunoglobulin light chain expression and
      L1/L2 blast morphology (French-American-British Classification) are rare. The
      poor prognosis of lymphoblastic leukemia in children under 1 year of age is
      attributed largely to rearrangements involving the mixed lineage leukemia (mll,
      also known as all1, htrx, trx1, or hrx) gene that occur with increased frequency
      in this population. Mll-rearranged cases with a mature B-cell phenotype are rare.
      The authors describe an infant with mature B-cell lymphoblastic leukemia with an
      mll rearrangement and L1/L2 cytomorphology and discuss the clinical, genetic, and
      immunophenotypic features in the context of previously reported cases.

PMID- 15454842
TI  - Intravenous ketamine infusion as an adjuvant to morphine in a 2-year-old with
      severe cancer pain from metastatic neuroblastoma.
AB  - A 2.8-year-old female patient (11.6 kg) was admitted to the hospital for
      uncontrolled pain and swelling in the left leg relating to a metastatic
      neuroblastoma. Initially, her pain was managed with oral morphine 2 mg (approx.
      0.2 mg/kg) every 4 hours. Because she was quite somnolent but still in
      significant pain, analgesia was then changed to methadone 1 mg orally every 6
      hours (approximately 0.1 mg/kg/dose) and was eventually increased over 36 hours
      to 2 mg every 6 hours (approximately 0.2 mg/kg/dose). She received oral methadone
      0.6 mg (approximately 0.05 mg/kg) every 4 hours as needed for breakthrough pain.
      She continued to have severe pain and experienced side effects, including
      respiratory depression, sedation, visual hallucinations, and vomiting. An
      intravenous ketamine infusion was started at 100 microg/kg/hour. Regular opioid
      administration was ceased, but she was given intravenous morphine 0.5 to 0.75 mg
      for breakthrough pain. She required only zero to three doses of breakthrough
      morphine per day, initially. After starting the ketamine infusion, her pain
      control improved and her symptoms of opioid toxicity abated. She was more alert
      and able to partake in limited activities. As a result of pain from progressive
      disease, the ketamine infusion was increased to 200 microg/kg/hour after 6 days
      with positive results. Her condition continued to deteriorate. An intravenous
      morphine infusion was initiated 2 weeks after starting the ketamine infusion and
      was eventually increased to 50 microg/kg/hour. One week later, she died with
      reasonable pain control. This case illustrates the use of ketamine as an
      effective analgesic in an adjuvant setting in a pediatric patient with advanced
      poorly controlled cancer pain. Ketamine not only eased the child's suffering
      while preserving life but also improved her quality of life by maintaining the
      child's ability to communicate and engage in activities.

PMID- 15454843
TI  - Thymoma in children: report of two cases and review of literature.
AB  - Thymoma is an uncommon tumor of childhood. Stage of the tumor is an independent
      prognostic factor for survival. Surgery is the treatment of choice for stage I
      and stage II tumors. Chemotherapy is reserved for patients with refractory or
      metastatic disease. Thymomas are moderately radiosensitive. However, radiation
      therapy is not an attractive option for children due to its side-effects on
      developing organs. The authors describe 2 children with completely encapsulated
      thymoma who were successfully treated with surgery alone. Both patients remain
      free of disease 3 years after surgery. One of the patients also has nevus
      sebaceous. The authors also discuss the possible association between the two
      disease entities.

PMID- 15454844
TI  - Fatal hepatic failure secondary to acute herpes simplex virus infection.
AB  - Acute hepatitis with severe hepatic failure is an uncommon manifestation of
      herpes simplex virus (HSV) infection. It has been described in both
      immunocompromised and immunocompetent patients and is usually fatal. Due to the
      better survival after acyclovir treatment in a few reported cases, physicians
      need to be aware of the characteristic clinical abnormalities so that early
      diagnosis and treatment can be implemented. The authors describe an adolescent
      diagnosed with Hodgkin disease who developed fatal hepatic failure secondary to
      acute HSV. Typical signs and symptoms in patients at risk, when there is no other
      obvious cause of fulminant hepatitis, should lead to early empirical treatment
      with acyclovir.

PMID- 15454845
TI  - Parvovirus B19 infection presenting as pre-B-cell acute lymphoblastic leukemia: a
      transient and progressive course in two children.
AB  - Parvovirus B19 is the causative agent of various forms of hematologic diseases
      such as aplastic crisis in patients with hemolytic anemia, aplastic anemia,
      hypoplastic anemia, and idiopathic thrombocytopenic purpura. In addition,
      parvovirus B19 infection may precede or be associated with acute lymphoblastic
      leukemia (ALL). The authors present two cases of parvovirus B19 infection and
      bone marrow infiltration with pre-B-cell lymphoblasts; one patients was diagnosed
      as having ALL, and the other patient, with neurologic findings, showed total
      resolution of the blastic morphology and phenotype.

PMID- 15454846
TI  - Neonatal paratesticular neuroblastoma misdiagnosed as in utero torsion of testis.
AB  - Reports of neuroectodermal primary scrotal tumors are scarce. Primary
      paratesticular neuroblastomas seem even rarer, and only five infants with this
      condition have been previously described. To the authors' knowledge, this would
      be the first report of a neonatal congenital paratesticular neuroblastoma.
      However, the authors postulate that ischemic compressive features in testis could
      lead to misdiagnosis as testicular torsion and the condition could usually go
      undetected. A newborn male baby with a left scrotal tumefaction was referred to
      the authors in May 2003. Doppler ultrasonography findings were inconclusive, and
      a diagnosis of intrauterine torsion of the testis was suspected. Surgery showed a
      paratesticular mass with a small attachment to an intra-abdominal epiploon.
      Pathologic examination clearly established the diagnosis of neuroblastoma.
      Cytogenetic findings (no amplification of N-myc oncogene, aneuploidy, and no
      deletion of chromosome 1p) were favorable. As the tumor was classified as
      International Neuroblastoma Staging System stage I, no additional chemotherapy
      was administered. All markers showed a progressive decrease, and herniorrhaphy
      and orchidopexy of the contralateral side were performed at 4 months of age. The
      patient was tumor-free at 11 months follow-up.

PMID- 15454847
TI  - Alveolar rhabdomyosarcoma with concurrent metastases to bone marrow and lymph
      nodes simulating acute hematologic malignancy.

PMID- 15454848
TI  - Failure to demonstrate myocardial protective effects of the ultra short-acting
      calcium antagonist clevidipine in a closed-chest reperfusion porcine model.
AB  - Restoration of myocardial perfusion is essential in acute myocardial infarction
      for the salvaging of myocardial tissue. However, reperfusion per se can provoke
      myocardial necrosis within the jeopardized tissue. Yet, no intervention has been
      successfully applied to the clinical situation in this matter. Clevidipine, an
      ultra-short acting calcium antagonist, has, in open-chest animal models, shown to
      reduce the extent of reperfusion injury. In the present study we intended to
      reproduce those findings in a closed-chest porcine model with a clinically
      applicable set up. Pigs were subjected to balloon occlusion of the left anterior
      descending coronary artery (LAD) for 45 minutes. During 25 minutes, starting 1
      minute prior to reperfusion, clevidipine, Intralipid, or saline was infused
      antegradely into the endangered myocardium. As no significant effects on infarct
      size were achieved, the model was modified. In a second phase, different
      anesthesias were evaluated addressing the same issue. Nonetheless no significant
      effects on infarct size were observed. Different techniques of occluding LAD, in
      an open-chest model, were investigated in a third phase, and revealed no
      significant differences between the techniques. However, when comparing all the
      closed- versus open-chest models, significant reduction in infarct size by the
      use of clevidipine was only obtained in the open-chest models. We could not
      demonstrate any significant myocardial protective effect with clevidipine in our
      porcine, closed-chest, acute infarct, and reperfusion model. However, in a
      modified open-chest model we obtained significant reduction in infarct size.
      Further studies are required to explain the discrepancies.

PMID- 15454849
TI  - In vitro inhibitory effect of lercanidipine on cholesterol accumulation and
      matrix metalloproteinases secretion by macrophages.
AB  - Plaque rupture and thromboembolism play a major role in atherosclerotic acute
      syndrome. Experimental studies have demonstrated the potential direct anti
      atherosclerotic effects of calcium antagonists. We investigated the in vitro
      effect of lercanidipine (REC 15/2375), a third-generation, highly lipophilic
      calcium antagonist on cholesterol metabolism and matrix metalloproteinases
      secretion in macrophages, two functions that predispose plaques to rupture.
      Lercanidipine (10(-6)-10(-5) M) inhibited cholesterol esterification in
      macrophages and reduced cellular free and esterified cholesterol accumulation
      from acetylated LDL (63%, 62% of control P < 0.05, respectively). In addition,
      lercanidipine inhibited the release of metalloproteinases in the extracellular
      medium (50% and 95% inhibition at 10(-5) M for MMP-9 and MMP-2, respectively).
      Experiments performed with lercanidipine enantiomers or other dihydropyridine
      derivatives, endowed with different lipophilicity and affinity for calcium
      channels, indicated that the above effects could be related to the lipophilic,
      but not to the calcium channel blocking properties of these molecules. When
      cells, after exposure to the drug, were allowed to equilibrate, lercanidipine
      inhibitory action could be observed at initial concentrations as low as 10(-9) M,
      which is the actual concentration range observed in plasma in clinical settings.
      In conclusion, our data indicate that lercanidipine may exert potent anti
      atherosclerotic effects by inhibiting macrophage functions involved in plaque
      stability.

PMID- 15454850
TI  - Hyperglycemic conditions affect shape and Ca2+ homeostasis of mitochondria in
      endothelial cells.
AB  - In this study the contribution of alternating architecture and Ca2+ handling of
      mitochondria to cytosolic Ca2+ homeostasis was elucidated under normoglycemic and
      hyperglycemic (HGC) conditions in the human endothelial cell line EA.hy926.
      Exposure of endothelial cells to hyperglycemic medium elevated basal cytosolic
      free Ca2+ concentration ([Ca2+]cyto), the histamine-initiated cytosolic Ca2+
      signaling, and the mitochondrial Ca2+ content after cell stimulation. The latter
      was possibly due to the prolonged mitochondrial Ca2+ elevation in response to
      agonists found in HGC-pretreated cells. Moreover, under HGC mitochondrial free
      radical production was increased and mitochondrial shape changed from a mainly
      tubular, highly interconnected network toward multiple, isolated singular
      structures. Such changes could not be correlated with HGC-induced alterations of
      cytosolic Ca2+ signaling that became normalized with antimycin A, an inhibitor of
      the respiratory chain. These data suggest that although mitochondrial structure
      changes considerably during HGC, alterations in cytosolic Ca2+ signaling are more
      likely due to the enhanced energy status/metabolism of the mitochondria. On the
      other hand, in normoglycemic cells of unforced fragmentation of mitochondria
      yielded elevated basal [Ca2+]cyto, while the global Ca2+ signaling in response to
      histamine remained unchanged. Thus, mitochondrial architecture (ie, tubular
      versus fragmented structure) per se does not have a detectable impact on agonist
      initiated global cytosolic Ca2+ signaling, while this organelle represents an
      early target in hyperglycemia leading to alterations in cytosolic Ca2+ signaling.

PMID- 15454851
TI  - Up-regulated neuronal nitric oxide synthase compensates coronary flow response to
      bradykinin in endothelial nitric oxide synthase-deficient mice.
AB  - It has been reported that endothelium-dependent relaxations are preserved in
      isolated coronary arteries of endothelial nitric oxide synthase-deficient (eNOS-/
      ) mice with a possible involvement of nNOS. However, it remains to be examined
      whether nNOS compensates coronary flow response in a beating heart of eNOS-/-
      mice and if so, whether and where nNOS is up-regulated. Coronary flow response to
      bradykinin was examined in Langendorff-perfused hearts from WT and eNOS-/- mice.
      Bradykinin-induced coronary flow was greater in eNOS-/- mice than in WT mice, and
      indomethacin had no inhibitory effect on it. Bradykinin receptor antagonist HOE
      140 abolished the bradykinin response in both strains. Non-selective NOSs
      inhibitor L-NNA inhibited the bradykinin-induced coronary flow in both strains,
      whereas specific inhibitors of nNOS, SMTC, and 7-NI, significantly attenuated the
      coronary flow response only in eNOS-/- mice. A guanylate cyclase inhibitor ODQ
      also attenuated the bradykinin response in eNOS-/- mice. Immunohistochemistry
      revealed the presence of nNOS mainly in coronary vascular smooth muscle cells
      (VSMCs) in both strains and Western blot analysis demonstrated a marked increase
      in cardiac nNOS expression in eNOS-/- mice. These results indicate that nNOS
      compensates coronary flow response to bradykinin in eNOS-/- mice, for which up
      regulation of nNOS in VSMCs may be involved.

PMID- 15454852
TI  - Inhibitory effect of candesartan and rosuvastatin on CD40 and MMPs expression in
      apo-E knockout mice: novel insights into the role of RAS and dyslipidemia in
      atherogenesis.
AB  - BACKGROUND: There is increasing evidence of cross-talk between renin-angiotensin
      system (RAS) and dyslipidemia in atherogenesis mediated via activation of
      inflammatory cascade, involving CD40 and matrix metalloproteinases (MMPs). We
      postulated that inhibition of RAS with candesartan and dyslipidemia with
      rosuvastatin would have additive inhibitory effect on CD40 and MMPs expression
      and atherogenesis. METHODS AND RESULTS: Apo-E knockout mice were fed high
      cholesterol diet alone, or with candesartan or rosuvastatin or both. C57BL/6J
      mice on regular mice chow served as control. Twelve weeks later, apo-E knockout
      mice with high-cholesterol diet had extensive atherosclerosis, whereas C57BL/6J
      mice had no atherosclerosis. Candesartan and rosuvastatin alone decreased the
      extent of atherosclerosis. However, the combined feeding of candesartan and
      rosuvastatin reduced atherosclerosis in an additive fashion. The expression of
      CD40 and MMPs was found to be up-regulated in apo-E knockout mice. While
      candesartan and rosuvastatin each had a small inhibitory effect on the expression
      of CD40 and MMPs, the combination completely blocked the up-regulation of these
      inflammatory mediators. CONCLUSION: This study, for the first time, demonstrates
      that the combination of candesartan and rosuvastatin markedly affects the
      expression of CD40 and MMPs, resulting in a greater anti-atherosclerotic effect.

PMID- 15454853
TI  - Thyroid hormone analog, DITPA, improves endothelial nitric oxide and beta
      adrenergic mediated vasorelaxation after myocardial infarction.
AB  - This study was designed to determine if the thyroid hormone analog 3,5
      diiodothyropropionic acid (DITPA), now in clinical trials for heart failure,
      alters endothelial function after myocardial infarction (MI). Three weeks after
      MI, adult Sprague-Dawley rats were randomly assigned to DITPA (375 microg/100 g
      subcutaneous) or no treatment of 3 weeks. In MI rats, left ventricular (LV) end
      diastolic pressure and LV dP/dt decreased (P < 0.05). DITPA did not change MAP
      (87 +/- 10 versus 90 +/- 7 mm Hg) or LV end-diastolic pressure (23 +/- 3 versus
      19 +/- 9 mm Hg) but did lower (P < 0.05) LV dP/dt (4,633 +/- 797 versus 3,650 +/-
      1,236 mm Hg/s). In aortic segments from MI rats, DITPA enhanced the acetylcholine
      dependent vasorelaxation (59 +/- 11% at 10(-4) M, P < 0.05) and isoproterenol
      induced vasorelaxation (57 +/- 13% at 10(-4) M, P < 0.05). The increases in
      vasorelaxation were blocked with l-NAME and restored with L-arginine. Treatment
      with DITPA increased (P < 0.05) eNOS protein content in aortic tissue from sham
      rats (3.8 +/- 2.8 to 44.5 +/- 7.1 integrated intensity units (II)/microg) and in
      MI rats (5.3 +/- 3.4 to 28.3 +/- 8.9 II/microg). In endothelial cells, 24 hours'
      treatment with DITPA (10 microM) increased (P < 0.01) eNOS protein expression
      from 22.1 +/- 4.8 to 52.7 +/- 16.8 II/microg protein and DITPA (20 microM)
      increased eNOS to 49.1+/- 15.2 II/microg protein. The thyroid analog DITPA
      enhances endothelial nitric oxide and beta-adrenergic-mediated vasorelaxation by
      increasing nitric oxide in the vasculature.

PMID- 15454854
TI  - A protein tyrosine phosphatase inhibitor accelerates angiogenesis in a rat model
      of hindlimb ischemia.
AB  - Vascular endothelial growth factor (VEGF) receptor-2 (KDR/flk-1) has a tyrosine
      kinase domain and, once activated, induces the autophosphorylation of the
      tyrosine residues. The phosphorylated KDR/flk-1 can be a substrate for
      intracellular protein tyrosine phosphatases (PTPs). In the present study, we have
      examined whether the PTP inhibitor sodium orthovanadate (SOV) activates KDR/flk-1
      and accelerates angiogenesis in a rat model of hindlimb ischemia. The left
      femoral artery was exposed and excised to induce limb ischemia. The PTP activity
      in ischemic adductors increased, whereas SOV significantly suppressed the
      increase in the activity. Tyrosine phosphorylation of KDR/flk-1 and Akt
      phosphorylation significantly increased in the muscles injected with SOV compared
      with those injected with saline. The amount of VEGF increased in both the muscles
      injected with SOV and those injected with the saline but did not differ
      significantly. At 21 days after the induction of ischemia, immunohistochemical
      studies demonstrated that muscles injected with SOV showed significantly
      increased capillary density compared with those injected with saline. In a rat
      model of hindlimb ischemia, not only VEGF but also PTP, which might impair
      angiogenesis, increased. SOV activated KDR/flk-1 and accelerated angiogenesis.
      Thus, a PTP inhibitor can be a new drug for therapeutic angiogenesis in
      peripheral ischemic diseases.

PMID- 15454855
TI  - Inotropic and lusitropic effects induced by the inhibitory factor of the Na/Ca
      exchanger are not mediated by the beta-adrenergic activation.
AB  - Recently, an endogenous inhibitory factor (NCXIF) of the cardiac Na/Ca exchanger
      (NCX1) has been isolated, purified, and preliminary characterized. Here, we
      demonstrate that low doses of NCXIF (10(-7)10(-8) M) induce strong inotropic
      effects in the guinea and rat ventricle strips, while having no detectable
      effects in the atria even at 10(-5) M. The inotropic effects of NCXIF are species
      specific; the rat ventricle muscle is 20 to 50 times more sensitive to varying
      doses of NCXIF than the guinea pig. On the other hand the extent of maximal
      inotropic response is more prominent in the guinea pig model (up to 6-fold
      enhancement) than in the rat (up to 2-fold enhancement). The NCXIF accelerates
      the single-twitch relaxation (lusitropic effect) in dose-dependent manner,
      reaching approximately 2-fold shortening of twitch width at saturating doses. The
      dose-dependence curves of lusitropic and inotropic effects exhibit a reciprocal
      relationship, meaning that these two effects might share common mechanisms. To
      test a possible involvement of catecholamines, the effects of NCXIF were examined
      in the presence or absence of beta-adrenergic blocker, deralin. The saturating
      doses of deralin (1- 3 microM) do not alter either the NCXIF-induced acceleration
      of relaxation or twitch enhancement, meaning that the NCXIF effects cannot be
      mediated by occasional release of endogenous catecholamines. The capacity of
      NCXIF to modulate the ventricle contractility unconnectedly to the beta
      adrenergic activation may provide new rational clues for future pharmacological
      interventions.

PMID- 15454856
TI  - Timing of erythropoietin treatment for cardioprotection in ischemia/reperfusion.
AB  - Erythropoietin (EPO) is a hormone known to stimulate hematopoiesis. However,
      recent research suggests additional properties of EPO, such as protection against
      ischemia/reperfusion (I/R) injury in various tissues. We studied the effect of
      timing of EPO administration on cardioprotection during I/R in the heart. Male
      Sprague-Dawley rats were subjected to 45 minutes of coronary occlusion, followed
      by 24 hours of reperfusion. Animals were randomized to receive saline or single
      dose of EPO (5,000 IU/kg) either 2 hours before I/R, at the start of ischemia, or
      after the onset of reperfusion. The ratio of infarct area/area at risk
      (planimetry), left ventricular (LV) function (pressure development), and
      apoptosis (number of active caspase-3 positive cells) were determined after 24
      hour reperfusion. Administration of EPO during different time points resulted in
      a 19 to 23% (P < 0.05) reduction in the infarct area/area at risk, which was
      accompanied by a trend toward better LV hemodynamic parameters. Apoptosis was
      significantly attenuated in groups treated with EPO at the start of ischemia (29%
      reduction) and after the onset of reperfusion (38%), and to a lesser extent (16%)
      in the group pre-treated with EPO. Thus, in vivo administration of EPO at
      different time points protects the myocardial structure and preserves cardiac
      function during I/R. Cardioprotective effect of EPO is associated with inhibition
      of apoptosis.

PMID- 15454857
TI  - Changing characteristics of patients with vasospastic angina in the era of new
      calcium channel blockers.
AB  - In the 1980s, clinical characteristics and long-term prognosis of patients with
      vasospastic angina (VSA) were investigated; however, they remain to be updated
      after the introduction of new calcium channel blockers, benidipine and
      amlodipine, in 1990s. Our patient cohort registered 726 patients with VSA from
      January 1980 to December 2002. Before and after 1990, 138 and 527 patients were
      respectively entered in this study with a follow-up rate of 92%. Most of the
      patients were treated with calcium channel blockers, while benidipine and
      amlodipine were used in 28% and 21% of them only after 1990. Survival without
      cardiovascular events (96% versus 96%) at 5 years remained good before and after
      1990. The presence of significant coronary stenosis had a negative prognostic
      impact both before and after 1990, whereas after 1990, diabetes mellitus,
      smoking, and a history of myocardial infarction became more influential. Among
      the calcium channel blockers, benidipine showed a better prognosis. These results
      suggest that in the era of new calcium channel blockers, the prognosis of
      patients with VSA remains good with more prognostic impact of diabetes mellitus,
      smoking, and a history of myocardial infarction and that benidipine might have
      some better prognostic effects.

PMID- 15454858
TI  - p38 alpha mitogen-activated protein kinase inhibition improves cardiac function
      and reduces myocardial damage in isoproterenol-induced acute myocardial injury in
      rats.
AB  - p38 mitogen-activated protein (MAP) kinase is activated during ischemic/hypoxic
      myocardial injury. However, the role of activated p38 MAP kinase on cardiac
      function after myocardial injury is not well understood. In the present study, we
      investigated the cardioprotective effects of p38 MAP kinase inhibition in a rat
      model of acute myocardial injury, induced by subcutaneous injection of
      isoproterenol (ISO, 20 mg/kg/d for 3 days). A synthetic p38 alpha MAP kinase
      inhibitor, SD-282 (40 mg/kg) or vehicle (0.25% Tween 80 in saline) was given
      intraperitoneally twice a day for 3 days, concomitant with ISO treatment. Cardiac
      function, systolic blood pressure, gene expression including collagen I and III,
      fibronectin and COX-2, and the myocardial injury were analyzed. Results showed
      that administration of SD-282 remarkably improved ISO-induced reduction of
      cardiac function with increases in ejection fraction (P < 0.001), cardiac output
      (P < 0.05), stroke volume (P < 0.001), and cardiac index (P < 0.01). SD-282
      abolished ISO-induced reduction of systolic blood pressure (106.7 +/- 2.2 versus
      123.1 +/- 5.3 mm Hg, P < 0.05). The ISO-induced expression of COX-2, collagen I
      and III, and fibronectin genes was reduced significantly (P < 0.05 in all cases)
      by administration of SD-282. The myocardial injury induced by ISO was
      significantly reduced by the treatment of SD-282 as judged by the reduction of
      myocardial necrosis. Data suggest that p38 alpha MAP kinase may be involved in
      the pathogenesis of cardiac dysfunction in ischemic myocardial injury. Inhibition
      of this enzyme may improve cardiac function and protect myocardium from
      ischemic/hypoxic injury that occurs during ischemic heart disease.

PMID- 15454859
TI  - In vitro and in vivo antithrombotic activity of PD-198961, a novel synthetic
      factor Xa inhibitor.
AB  - PD-198961, 3-(4-5-[(2R,6S)-2,6-dimethyltetrahydro-1(2H)-pyridinyl]pentyl-3-oxo
      3,4-dihydro-2-quinoxalinyl)-4-hydroxybenzenecarboximidamide, is a novel,
      synthetic factor Xa inhibitor with a Ki of 2.7 nM against human factor Xa. The
      aim of the present study was to evaluate the pharmacokinetic profile and
      antithrombotic efficacy of PD-198961 in rabbits. When tested in vitro, PD-198961
      doubled prothrombin time (PT) and activated partial thromboplastin time (aPTT) at
      concentrations of 0.13 and 0.32 microM in human plasma, 0.2 and 0.09 microM in
      rabbit plasma, 0.3 and 0.4 microM in dog plasma, respectively. Intravenous
      administration of PD-198961 at 1 mg/kg over 30 minutes resulted in a maximal
      prolongation in PT and aPTT of 4.9 +/- 0.4 and 4.1 +/- 0.9-fold of baseline,
      respectively. The peak plasma concentration of PD-198961 was 977 +/- 96 ng/ml.
      The anticoagulant effect of PD-198961 was readily reversible; coagulation
      parameters and plasma concentration returned to near baseline 15 minutes after
      cessation of infusion. There was a good correlation between PT prolongation and
      plasma concentration of PD-198961 (r = 0.93). In an FeCl3-induced model of
      arterial thrombosis in rabbits, the antithrombotic effects of PD-198961 were
      compared with that of LB-30057, a direct thrombin inhibitor, and enoxaparin, a
      low molecular weight heparin (LMWH). PD-198961 dose dependently increased the
      time to occlusion (TTO), reduced thrombus weight (TW), and decreased the
      incidence of occlusion. When administered at 3.0 microg/kg/min IV, PD-198961
      prolonged TTO from 28 +/- 5 minutes (control) to 120 +/- 0 minutes (P < 0.001)
      and reduced TW from 9.9 +/- 1.5 mg (control) to 2.8 +/- 0.9 mg (P < 0.01). PD
      198961 also dose dependently inhibited ex vivo plasma FXa activity. At the
      highest dose tested, PD-198961 increased aPTT to 1.4 +/- 0.1-fold of baseline
      (compared with 1.5 +/- 0.1 and 2.8 +/- 0.3-fold of baseline for LB-30057 [CI
      1028] and enoxaparin, respectively), and had modest effects on bleeding time (<
      or = 2-fold). These results indicate that PD-198961 is a potent FXa inhibitor and
      an effective antithrombotic agent at doses that produce only modest changes in
      normal hemostasis.

PMID- 15454860
TI  - Prophylactic effect of intravenous nicorandil on perioperative myocardial damage
      in patients undergoing off-pump coronary artery bypass surgery.
AB  - Nicorandil, ATP sensitive potassium channel opener, is shown to reduce coronary
      events for patients with stable angina. The present study was designed to examine
      the protective potential of nicorandil for patients undergoing off-pump coronary
      artery bypass grafting. Twenty-four patients undergoing off-pump coronary artery
      bypass grafting were randomly assigned to two groups, one receiving continuous
      infusion of nicorandil (1.0 microg.kg(-1).min(-1)) (n = 12) through anesthesia to
      next day and the other receiving no nicorandil for control (n = 12). For
      assessing myocardial injury, heart type fatty acid binding protein, troponin T,
      and creatine kinase MB isoform were determined during the first 15 hours after
      reperfusion. The concentration of heart type fatty acid binding protein in the
      nicorandil group was significantly lower than that in the control group. On the
      other hand, the concentrations of troponin T and creatine kinase MB isoform in
      the nicorandil group were lower than those in the control group, but the
      differences did not reach statistical significance. Furthermore, nicorandil did
      not affect the patients' hemodynamic variables. Our data suggest that the
      infusion of nicorandil provides small myocardial protection without affecting
      hemodynamic parameters during perioperative treatment of patients undergoing off
      pump coronary artery bypass grafting.

PMID- 15454861
TI  - Acetylcholine-induced relaxation of rabbit basilar artery in vitro is rapidly
      reduced by reactive oxygen species in acute hyperglycemia: role of NADPH oxidase.
AB  - We examined the effects of acute hyperglycemia on the function of rabbit cerebral
      arteries in vitro. It was hypothesized that increased formation of reactive
      oxygen species (ROS) could occur, which could explain how hyperglycemia
      aggravates certain pathologic situations such as cerebral ischemia. Three
      millimeter basilar artery segments were incubated in either normoglycemic (NG,
      5.5 mM D-glucose) or hyperglycemic (HG, 25 mM D-glucose) solution containing
      3.10(-6) M indomethacin. After 90 minutes equilibration, a test (=T1) of
      relaxation to acetylcholine (Ach) at three concentrations was performed on
      histamine-precontracted segments. Three further identical tests were performed
      (T2-T4), after 30-minute rest periods. Ach responses in NG solution were stable,
      whereas those in HG solution, although greater at T1, fell progressively from one
      test to the next (P < 0.0001 versus NG), whereas nitroprusside responses did not
      change. In separate experiments, this time-dependent fall in Ach responses was
      significantly prevented by superoxide dismutase (SOD) plus catalase (P = 0.0003),
      but not by SOD alone. It was also significantly prevented by the NAD(P)H oxidase
      inhibitors diphenyleneiodonium (P = 0.020) and apocynin (P = 0.0179), but not by
      allopurinol (xanthine oxidase inhibitor). Control experiments with l-glucose
      ruled out a hyperosmotic or non-specific glucose effect. We conclude that, in HG
      solution in vitro, rapidly increasing ROS production largely derived from NAD(P)H
      oxidase reduced relaxation to acetylcholine. The rapidity of this effect suggests
      that the function of these arteries may be affected during brief periods of
      hyperglycemia in vivo.

PMID- 15454863
TI  - [Athetosis or dystonia?].
AB  - The term athetosis has progressively disappeared from the anglo-saxon literature
      which considers that athetosis is part of the spectrum of dystonia. These two
      clinical entities can be distinguished, however. Athetosis can be identified,
      searching for subtle semiological traits, in particular at the level of the hand.
      The earlier appearance of athetosis may be result from its onset during the early
      phases of development of the central nervous system. Despite its rarity, the
      clinical diagnosis of athetosis is important to consider from a prognostic point
      of view. Indeed, it results from brain lesions, and is therefore not a hereditary
      disorder as it may be the case for dystonia, and its evolution is relatively
      stable. The efficacy of treatments used in patients with dystonia, in particular
      high frequency pallidal stimulation, remains to be assessed in patients with
      athetosis. The concept of athetosis is still helpful in clinical practice.

PMID- 15454864
TI  - [The role of nutritional factors on the structure and function of the brain: an
      update on dietary requirements].
AB  - The brain is an organ elaborated and functioning from substances present in the
      diet. Dietary regulation of blood glucose level (via ingestion of food with a low
      glycemic index ensuring a low insulin level) improves the quality and duration of
      intellectual performance, if only because at rest the adult brain consumes 50 p.
      100 of dietary carbohydrates, 80 p. 100 of them for energy purposes. The nature
      of the amino acid composition of dietary proteins contributes to good cerebral
      function; tryptophan plays a special role. Many indispensable amino acids present
      in dietary proteins help to elaborate neurotransmitters and neuromodulators.
      Omega-3 fatty acids provided the first coherent experimental demonstration of the
      effect of dietary nutrients on the structure and function of the brain. First it
      was shown that the differentiation and functioning of cultured brain cells
      requires omega-3 fatty acids. It was then demonstrated that alpha-linolenic acid
      (ALA) deficiency alters the course of brain development, perturbs the composition
      and physicochemical properties of brain cell membranes, neurones,
      oligodendrocytes, and astrocytes (ALA). This leads to physicochemical
      modifications, induces biochemical and physiological perturbations, and results
      in neurosensory and behavioral upset. Consequently, the nature of polyunsaturated
      fatty acids (in particular omega-3) present in formula milks for infants
      (premature and term) conditions the visual and cerebral abilities, including
      intellectual abilities. Moreover, dietary omega-3 fatty acids are certainly
      involved in the prevention of some aspects of cardiovascular disease (including
      at the level of cerebral vascularization), and in some neuropsychiatric
      disorders, particularly depression, as well as in dementia, notably Alzheimer's
      disease. Their deficiency can prevent the satisfactory renewal of membranes and
      thus accelerate cerebral aging. Iron is necessary to ensure oxygenation, to
      produce energy in the cerebral parenchyma, and for the synthesis of
      neurotransmitters. The iodine provided by the thyroid hormone ensures the energy
      metabolism of the cerebral cells. The absence of iodine during pregnancy induces
      severe cerebral dysfunction, leading to cretinism. Manganese, copper, and zinc
      participate in enzymatic mechanisms that protect against free radicals, toxic
      derivatives of oxygen. The use of glucose by nervous tissue implies the presence
      of vitamin B1. Vitamin B9 preserves memory during aging, and with vitamin B12
      delays the onset of signs of dementia, provided it is administered in a precise
      clinical window, at the onset of the first symptoms. Vitamins B6 and B12, among
      others, are directly involved in the synthesis of neurotransmitters. Nerve
      endings contain the highest concentrations of vitamin C in the human body. Among
      various vitamin E components, only alpha-tocopherol is involved in nervous
      membranes. The objective of this update is to give an overview of the effects of
      dietary nutrients on the structure and certain functions of the brain.

PMID- 15454865
TI  - [Kinematic evaluation of dystonic syndromes in patients treated with deep brain
      stimulation].
AB  - INTRODUCTION: Quantification of motor functions of patients with dystonic
      syndromes treated by chronic high frequency stimulation of the internal globulus
      pallidus is a challenge. OBJECTIVE: Through a series of clinical examples this
      paper shows that kinematic analysis of movements in dystonic syndromes treated by
      deep brain stimulation (DBS) is a complement to clinical evaluation. In addition,
      it provides valuable information for early detection of improvement or impairment
      of movements associated with modifications of stimulation parameters. METHOD:
      Thirteen dystonic patients and eleven reference subjects completed three tests
      (i.e., rest: lying supine; posture: standing with arms held in front (at shoulder
      height); and alternative movements: bimanual finger-to-nose test). These tests
      were recorded with an electromagnetic system quantifying movement kinematics
      (position) in three-dimensional space. RESULTS: From the recorded data, several
      indices were developed and provided a quantitative evaluation of movements during
      each test. In addition, a clinical evaluation (BMFDRS) was also completed. No
      correlation between clinical and kinematic evaluations was found. CONCLUSION: It
      is shown that kinematic analysis is a useful complement of clinical evaluation
      and can assist clinicians in monitoring the evolution of movements in dystonic
      patients treated by DBS in a simple, reliable and valid fashion.

PMID- 15454866
TI  - [The contribution of automatic anatomical matching of sequential brain MRI scans
      in the monitoring of multiple sclerosis lesions].
AB  - INTRODUCTION: Magnetic resonance imaging (MRI) has transformed management of
      patients with multiple sclerosis. The exact contribution of brain MRI remains a
      subject of debate, but it is generally considered to provide a more specific and
      more sensitive outcome measure for monitoring purposes and for testing new
      therapies. The choice of MRI techniques, and measurement reproducibility for
      multiple sclerosis brain lesions are not defined with precision for routine
      practice. There are many sources of error when comparing successive images which
      can be overcome to some extent with repositioning and image processing
      techniques. METHODS: We evaluated the impact of image repositioning on treatment
      decision-making for twelve relapsing remitting patients. Brain MRIs were
      performed every three months for a one-year period. Two neurologists interpreted
      the non-repositioned and repositioned images giving their analysis of changes in
      the lesions visualized on the T2 sequences and their therapeutic decisions.
      RESULTS: For the first neurologist, analysis of the non-repositioned images
      yielded six patients whose lesions had worsened while for the repositioned images
      there were only three. For the second neurologist, four patients had more lesions
      with the non-repositioned images and only three with repositioning. The
      subjective interpretations were the same for the two neurologists when they used
      repositioned images. CONCLUSIONS: Comparison by two neurologists of non
      repositioned and repositioned MRI, with no other image processing, affected the
      analysis and in certain cases propositions for treatment.

PMID- 15454867
TI  - [Systemic lupus erythematosus presenting with recurrent psychiatric
      disturbances].
AB  - INTRODUCTION: There is a wide range of non-specific symptoms that can reveal
      neurolupus, sometimes making diagnosis difficult. OBSERVATION: A 29-year-old man
      presented, from 1996 to 2002, three episodes of mood disorders with hetero
      aggression, preceded by seizures, which resolved completely. Repeated
      investigations were negative except for lymphopenia, an inflammatory
      cerebrospinal fluid and some rare non-specific areas of high intensity signals in
      the white matter on the brain MRI. After a six-year course, the patient was
      considered to have a severe mood disorder related to a schizoid personality. A
      new dot-blot search for antinuclear antibodies detected anti-Sm antibodies was
      positive, leading to the diagnosis of neuropsychiatric lupus since the patient's
      symptoms fulfilling four of the American Rheumatism Association criteria
      (neuropsychiatric events, lymphopenia, antinuclear and anti-Sm antibodies). The
      patient was given monthly pulses of cyclophosphamide and remained symptom free
      one year after the last flare up. CONCLUSIONS: Lupus can rarely be revealed by
      long-standing isolated psychiatric disorders. Search for auto-antibodies, using
      highly specialized techniques (western blot, dot blot) should be a routine
      practice since antibody titres fluctuate during the course of the disease;
      elevated titres may correlate with exacerbations. Considering the prominence and
      severity of these behavior disorders, systemic diseases may often be
      misdiagnosed.

PMID- 15454868
TI  - [The presentation of childhood systemic lupus erythematosus with neurological
      symptoms: three-case reports].
AB  - INTRODUCTION: neurological symptoms occurring during childhood, especially if
      unusual or recurrent, should attract attention. METHODS: We report three cases of
      childhood lupus revealed by neurological symptoms. RESULTS: Misdiagnosis was
      frequent and time from symptom onset to diagnosis of lupus reached up to six
      months. CONCLUSION: After careful history taking and physical examination,
      complementary tests should include erythrocyte sedimentation rate, blood count,
      platelets, and in some cases an immunological study with antinuclear antibodies.

PMID- 15454869
TI  - [Contribution of corticosteroid to the treatment of pain in the acute phase of
      Guillain-Barre syndrome].
AB  - INTRODUCTION: Pain is a common problem in both adults and children with Guillain
      Barre Syndrome (GBS). Corticosteroids are rarely used in the treatment of pain in
      the course of GBS, although some authors have pointed out their value for the
      treatment of neuropathic pain. We report four patients with GBS whose pain was
      rapidly relieved by administration of corticosteroids. METHODS: We reviewed
      retrospectively a series of four patients with GBS seen from September 2001 to
      February 2003. All patients had plexual (Case 3), trunkular (case 1), radicular
      (case 2) or focal (case 4) pain. Pain was treated with corticosteroids via oral
      (cases 1 and 2) or intravenous routes (cases 3 and 4). Corticoids where used
      after failure of other analgesic agents. RESULTS: Pain relief was obtained after
      the first administration and persisted even after tapering off steroid treatment.
      No particular complication was observed during treatment course. CONCLUSION: Our
      experience suggests that controlled studies should be set up to evaluate the
      place of corticosteroid treatment for the management of pain in patients with
      GBS.

PMID- 15454870
TI  - [Polymorphism of epilepsy associated with the A3243G mutation of mitochondrial
      DNA (MELAS): reasons for delayed diagnosis].
AB  - INTRODUCTION: Mitochondrial disease is a potential diagnosis in patients with
      epilepsy beginning in childhood or adolescence with a typical polymorphic
      presentation and preponderant occipital lobe seizures. Diagnosis may however be
      delayed in some patients with long-standing disease, particularly when cardinal
      mitochondrial symptoms are missing; clinical manifestations may be dissociated
      over time leading to genetic diagnostic tests being prescribed long after disease
      onset. OBSERVATION: We report the case of a 17 year old woman in whom the
      diagnosis of lipothymic episodes, migraine, idiopathic photo-sensitive
      generalized epilepsy, and partial occipital epilepsy complicated by occipital
      epileptic status were successively proposed because of the initial clinical
      presentation and the slow disease course. Eleven years after disease onset the
      diagnosis of progressive myoclonic epilepsy was made due to the occurrence of
      myoclonic jerks with giant SEPs associated with a cerebellar syndrome,
      deterioration of psychomotor performances and diffuse slowing of EEG activity
      with pseudo-periodic bursts of delta waves. Genetic analysis showed an A3243G
      mutation of mitochondrial DNA, usually correlated with the MELAS phenotype, while
      the clinical presentation of progressive myoclonic epilepsy was more suggestive
      of MERRF. CONCLUSION: Although each of the symptoms successively observed in this
      patient has been reported in MELAS, the slow course of the disease, which is
      unusual in this mutation, the absence of stroke-like episodes, and the
      polymorphism of the epilepsy all contributed to delayed final diagnosis.

PMID- 15454871
TI  - [Multiple sclerosis with sensory disturbances and hyperhidrosis of the hand].
AB  - INTRODUCTION: Hyperhidrosis may result from brain, spinal cord or peripheral
      nervous system injuries. We report the case of a 26-year-old patient who
      presented with sensorial disorders and focal hyperhidrosis of the right hand.
      OBSERVATION: MRI revealed multiple lesions very suggestive of active
      demyelinization. A lesion in the left paramedian posterior portion of the pons
      was enhanced after gadolinium infusion. The diagnosis of multiple sclerosis was
      suggested by MRI data and oligoclonal IgG bands on cerebrospinal fluid
      electrophoresis. CONCLUSIONS: Focal hyperhidrosis may be due to a lesion of the
      crossed sympathetic inhibitory tract. Although autonomic dysfunction is common
      during the late course of multiple sclerosis this case is, to our knowledge, the
      first report of focal hyperhidrosis revealing multiple sclerosis.

PMID- 15454872
TI  - [Ataxic sensory neuropathy and Lyme disease].
AB  - INTRODUCTION: The clinical spectrum of peripheral neuropathies in Lyme disease is
      very wide. We report a case which was revealed by an ataxic sensory neuropathy.
      OBSERVATION: A 77-year-old patient presented with a subacute ataxic sensory
      neuropathy which occurred 2 weeks after a skin lesion involving the right lower
      limb. He fully recovered after specific antibiotic treatment. EMG was suggestive
      of a predominantly axonal neuropathy. Diagnosis of Lyme disease was assessed by
      progressive elevation of serum antibodies, demonstration of a lymphocytic
      meningitis and intrathecal synthesis of antibodies. CONCLUSION: Lyme disease may
      be added to the list of diseases which may induce subacute sensory neuropathies.

PMID- 15454873
TI  - [Acute, isolated and reversible paralysis of the soft palate in childhood].
AB  - INTRODUCTION: Unilateral spinal and accessory palsy is uncommon in children. The
      main problem is the extensive exploration undertaken to achieve etiological
      diagnosis. OBSERVATION: We report two cases of transitory, unilateral, spinal and
      accessory palsy, associated in one case with homolateral hemi-pharyngeal palsy,
      that occurred in two previously healthy children. RESULTS: Few reports have been
      published in the literature to date. From those two cases and data of the
      literature, we suggest that the clinical presentation results from idiopathic
      peripheral nerve palsy. CONCLUSION: Further case reports would be useful to
      confirm the benign nature of this syndrome so that complementary investigations
      may be limited in future cases with a similar presentation.

PMID- 15454874
TI  - [Acute relapse in Charcot-Marie-Tooth 1B neuropathy: can protein P0 behave like
      an autoantigen?].
AB  - INTRODUCTION: The natural history of Charcot-Marie-Tooth neuropathy is marked by
      accentuated motor and sensitive deficits suggestive of acute polyradiculoneuritis
      or, more generally, chronic inflammatory demyelinizing polyneuropathy.
      OBSERVATION: A 41-year-old woman, with Charcot-Marie-Tooth (CMT) 1B neuropathy
      associated with a P0 gene mutation, developed several episodes of ataxia which
      resolved after intravenous administration of IgG or corticosteroids. CONCLUSION:
      The sudden increase of a motor or sensitive deficit in this patient with CMT type
      I led to two hypotheses: chance association between an inherited and an
      inflammatory neuropathy, or a dysimmune inflammatory reaction, the mutated
      protein acting like an autoantigen. These two hypotheses are discussed.

PMID- 15454875
TI  - [Chronic ergotism: spinal lesion and neuropathy].
AB  - INTRODUCTION: Neuropathologic manifestations due to chronic ergotism are rare.
      OBSERVATION: We report the case of a 40-year-old patient who presented clinical
      signs and symptoms of a spinal lesion and also the symptoms of neuropathy
      involving the right sciatic nerve, more precisely the internal and external
      popliteal nerves, following ingestion of methysergide. Complete recovery was
      achieved with calcium blocker treatment. CONCLUSION: Ergotism should be
      considered in patients treated by ergot alkaloids presenting an atypical clinical
      manifestations.

PMID- 15454878
TI  - [Cadasil].

PMID- 15454879
TI  - [The diagnostic approach to and management of pes cavus].

PMID- 15454880
TI  - [Central dopamine receptors: general considerations (Part 1)].
AB  - Specific protein G-coupled receptors mediate the effects of dopamine in its
      projection areas. Five dopaminergic receptors have been cloned, characterized and
      classified in two families, the D1-like family (D1- and D5-receptor subtypes) and
      the D2-like family (D2-, D3- and D4-receptor subtypes). These five dopamine
      receptor subtypes are characterized by their diversity in terms of transduction,
      distribution, pharmacology, functions, and regulation, leading to pleiotropic
      pathophysiological and pharmacological involvements in neuropsychiatric disorders
      underlain by a deregulation of the dopaminergic system.

PMID- 15454881
TI  - Peroxidase activity within circulating neutrophils correlates with pulmonary
      phenotype in cystic fibrosis.
AB  - Excess neutrophils are present in the airways of patients with cystic fibrosis
      (CF). Myeloperoxidase (MPO) activity of acid extracts of sputum is directly
      correlated with airflow obstruction in CF patients. We hypothesized that the
      sputum MPO was derived from the MPO of neutrophils that entered the airways from
      the circulation. Active MPO without protease activity injures airways. If MPO
      activity from circulating neutrophils that emigrate into the airways of these
      patients causes increased airway epithelial permeability and mucus-gland
      secretion, then (1) those patients with greater MPO activity per circulating
      neutrophil would be more likely to produce sputum and (2) the MPO activity per
      circulating neutrophil would positively correlate with airflow obstruction. We
      determined the MPO activity for both circulating and sputum neutrophils.
      Spirometry and respiratory cultures were obtained simultaneously with blood and
      sputum samples. CF patients with more MPO activity within their circulating
      neutrophils were more likely to produce sputum ( P =.001, chi 2 test), and the
      MPO activity per circulating neutrophil was positively correlated with airflow
      obstruction as measured on the basis of the ratio of 1-second forced expiratory
      volume to forced vital capacity ( P <. 03, Kruskal-Wallace test). These
      associations were independent of age, sex, the results of respiratory-tract
      culture, or protease activity in the circulating neutrophils. MPO activity in
      circulating neutrophils from CF patients homozygotic for the deletion of
      phenylalanine at position 508 in the CF transmembrane regulator protein is
      directly related to the severity of these patients' pulmonary disease. Our
      results are consistent with the hypothesis that circulating neutrophils deliver
      active MPO to the airway, producing airway injury and airflow obstruction in
      homozygotic delF508 CF patients.

PMID- 15454882
TI  - Solubility of cholesterol in the crystal-free gallbladder bile of gallstone
      patients.
AB  - Supersaturation of bile with cholesterol is generally considered the driving
      force of cholesterol precipitation. However, in most investigations the amount of
      cholesterol crystals is included in the calculation of the cholesterol saturation
      index (CSI). We therefore studied the solubility of cholesterol in crystal-free
      gallbladder bile from gallstone patients. Our results demonstrate significantly (
      P <.05) higher CSIs (1.4 +/- 0.5 and 1.4 +/- 0.4 vs 1.1 +/- 0.4, mean +/- SD) in
      crystal-free gallbladder bile from 66 patients with cholesterol stones and 21
      patients with mixed stones compared with those in 30 patients with pigment stones
      and a significant difference ( P <.001) in the amount of cholesterol in vesicles
      (19.2% +/- 13.7% and 14.3% +/- 11.6 % vs 4.2% +/- 5.9%) and of the crystal
      observation time (COT; 1-21 days, median 2 days and 1-21 days, median 3 days, vs
      3-21 days, median 21 days). We detected a positive correlation ( r =.24, P <.01)
      between the percentage of cholesterol in vesicles and the CSI and a negative
      correlation between COT and CSI ( r = -.23, P <.02 ) and COT and the percentage
      of cholesterol in vesicles ( r = -.52, P <.001 ). However, in 14 of 30
      gallbladder-bile specimens from patients with pigment stones but in just 5 of 21
      specimens from patients with mixed stones patients and 12 of 66 specimens from
      patients with cholesterol stones, the distribution of cholesterol in different
      phases (mixed micelles, vesicles, and crystals) was within the limits of
      solubility determined in previous studies of model bile. Therefore, in addition
      to the relative composition of biliary lipids, nonlipid components exert
      considerable influence on the solubility of cholesterol in the gallbladder bile
      of gallstone patients.

PMID- 15454883
TI  - Combined search for anti-beta2-glycoprotein I and anticardiolipin antibodies in
      antiphospholipid syndrome: contribution to diagnosis.
AB  - In this study we sought to assess (1) the diagnostic value of a combined search
      for anti-beta(2)-glycoprotein (abeta(2)-GPIs) and anticardiolipin antibodies
      (aCLs) in primary (APS I) and secondary (APS II) antiphospholipid syndrome and
      (2) the influence of the beta(2)-GPI preparation in the ELISA's results. abeta(2)
      GPI and aCL concentrations were assessed in 70 patients with APS and compared
      with those in 65 patients with systemic lupus erythematosus (SLE) without
      clinical features of APS. In APS patients (38 with APS I, 32 with APS II), the
      diagnosis had to have been made at least 3 years earlier; in subjects with SLE,
      the diagnosis had to have been made at least 5 years earlier. All serum samples
      were tested for abeta(2) -GPI with the use of an in-house ELISA with an abeta(2) 
      GPI preparation from human plasma. Samples negative for abeta(2) -GPI were
      controlled with 2 additional beta(2)-GPI preparations, 1 from human serum and 1
      from bovine serum. In APS, abeta(2)-GPIs were more frequent than in SLE (76% and
      15%, respectively; P <.0001), mainly with IgG isotype and with significantly
      higher levels than those found in SLE. The specificity for APS was 92% for IgG
      abeta(2)-GPIs and 68% for IgG aCLs. The highest association with APS was found
      for the combination of the 2 markers (odds ratio 29; 95% confidence interval 10
      76; P <.0001). Among the APS patients, 6 were positive for aCL only and remained
      negative regardless of which beta 2 -GPI preparation was used; 1 patient was aCL
      negative and only positive with human beta 2 -GPI. These data emphasize the
      heterogeneity of the APS immunologic profile and the diagnostic possibilities of
      both antibodies.

PMID- 15454884
TI  - Nitric oxide acts on the mitochondria and protects human endothelial cells from
      apoptosis.
AB  - Proliferation of small blood vessels in synovial tissues is one of the pathologic
      features of rheumatoid arthritis. In this study we tested the hypothesis that
      nitric oxide (NO) protects endothelial cells (ECs) against apoptogenic agents in
      vitro. Human umbilical-vein endothelial cells (HUVECs) were cultured with and
      without NO donor S -nitro- N -acetylpenicillamine (SNAP) and further incubated in
      the presence or absence of Z-leucine-leucine-leucine-aldehyde (LLL-CHO),
      etoposide, or C2-ceramide. After cultivation, apoptosis of HUVECs was quantified
      on the basis of disruption of mitochondrial transmembrane potential (DeltaPsim),
      activation of caspases, and the presence of hypodiploid DNA-positive cells.
      Treatment of HUVECs with LLL-CHO, etoposide, or C2-ceramide induced DeltaPsim,
      activation of caspase-3, caspase-8, and caspase-9 and the appearance of
      hypodiploid DNA-positive cells. NO production in HUVECs was clearly increased by
      SNAP. Apoptotic cell death in HUVECs induced by LLL-CHO, etoposide, and C2
      ceramide was significantly suppressed by SNAP treatment. HUVECs in vitro
      expressed Bcl-2, Bcl-xL, and Bax; however, expression was not changed by SNAP
      treatment in the presence or absence of LLL-CHO, etoposide, or C2-ceramide.
      Although the molecule(s) responsible for the protective effects of NO remains to
      be identified, our data imply that NO protects HUVECs against mitochondrial
      perturbation caused by apoptogenic agents. These results suggest that NO promotes
      endothelial-cell proliferation and angiogenesis in the synovial tissues of
      patients with rheumatoid arthritis and that NO may be a therapeutic target for
      rheumatoid arthritis.

PMID- 15454885
TI  - Arterial and venous smooth-muscle cells differ in their responses to
      antiproliferative drugs.
AB  - Arteriovenous polytetrafluoroethylene (PTFE) grafts used for hemodialysis often
      fail as the result of myointimal hyperplasia with vascular smooth-muscle-cell
      (SMC) proliferation. The stenotic lesions occur primarily at the graft-vein
      anastomosis and less frequently at the graft-artery anastomosis. To explore the
      potentials of pharmacologic agents in preventing hemodialysis-graft stenosis, we
      first examined the susceptibility of venous and aortic SMCs to 3
      antiproliferative drugs. Human aortic and saphenous-vein SMCs were cultured in a
      medium containing insulin, epidermal growth factor, fibroblast growth factor, and
      fetal bovine serum. Various concentrations of dipyridamole (0-100 microg/mL),
      paclitaxel (0-100 microg/mL), and tranilast (0-300 microg/mL) were added. After
      72 hours, we subjected the cells to a mitochondrial enzymatic
      (methylthiazoletetrazolium; MTT) assay and a bromodeoxyuridine (BrdU)
      incorporation assay as a means of assessing their proliferation. Dipyridamole,
      paclitaxel, and tranilast each inhibited the proliferation of aortic and venous
      SMCs in a dose-dependent manner ( P <.0001). Approximately 90% inhibition was
      achieved at dipyridamole concentrations of 75 microg/mL and greater in both MTT
      and BrdU assays; paclitaxel and tranilast were less effective. The venous SMCs
      were substantially more susceptible to inhibition by all 3 drugs than were the
      aortic SMCs in the MTT assay. The concentrations required to produce 50%
      inhibition (IC 50 ) in the venous cells were 5.8 microg/mL (11.5 micromol/L), 9.1
      microg/mL (10.7 micromol/L), and 37.4 microg/mL (114.3 micromol/L), respectively,
      for dipyridamole, paclitaxel, and tranilast. These concentrations were
      approximately 4.2, 5.3, and 3.0 times lower, respectively, than the corresponding
      IC 50 values for the aortic cells. The differences in IC 50 between the aortic
      and venous cells for the 3 drugs were less pronounced in the BrdU assay. The
      results of this study suggest that strategies for the prevention of stenosis
      should take into account the fact that lesions at venous anastomoses of
      arteriovenous grafts may respond differently to drugs than do those at arterial
      anastomoses.

PMID- 15454886
TI  - Soluble cathepsin-L: a marker of bone resorption and bone density?
AB  - We sought to evaluate cathepsin L serum levels in the peripheral blood of
      patients with low bone density. Blood samples from 60 patients (32 osteoporotic,
      28 osteopenic) and 16 healthy controls were taken and quantitative measurements
      of cathepsin L were performed with the use of a commercially available enzyme
      linked immunosorbent assay. Dual x-ray absorptionometry measurements and serum
      levels of alkaline phosphatase, bone-specific alkaline phosphatase, osteocalcin,
      parathyroid hormone, sexual hormones, and N -terminal crosslinks of type I
      collagen were examined. Group comparisons between patients with osteoporosis and
      controls showed significant differences with respect to cathepsin L ( t = -2.839;
      df = 29; P =.008). Osteoporosis treatment decreased the serum level of cathespsin
      L in a statistically significant fashion ( P =.002). These results suggest that
      the serum level of cathepsin L can serve as a marker of bone resorption and bone
      density.

PMID- 15454887
TI  - Hospital bioterrorism preparedness linkages with the community: improvements over
      time.
AB  - BACKGROUND: Strong linkages between hospitals and community response entities
      such as fire safety, law enforcement, emergency management agencies, emergency
      medical services, public health, and local government administration are an
      essential element of overall hospital preparedness. These pre-established
      relationships enable an integrated community response during an emergency.
      METHODS: This pilot study assessed changes in linkages between hospitals and key
      community entities related to preparedness for a bioterrorism (BT) event before
      and after the events of fall 2001. A 51-item questionnaire was mailed to two
      consecutive hospital samples scheduled for accreditation surveys (April-May 2001
      and May-June 2002; n=68 and n=97 responses, respectively). On-site visits by
      surveyors verified the presence of a plan addressing bioterrorism issues.
      RESULTS: Substantial improvement in collaborative planning for surge capacity and
      lab/pharmacy issues occurred. Hospital plans that addressed BT increased
      significantly (47.1% to 90.7%), as did awareness of community BT-related plans
      (48.5% to 74.2%). Hospitals that conducted a BT-related drill increased from
      19.1% to 48.5%. CONCLUSIONS: Adequate resources are needed, but opportunities
      remain to further improve collaborative planning, such as agreements with other
      hospitals on a single media spokesperson or development of a protocol for
      pharmaceutical distribution. Additional guidance is needed on expected levels of
      performance regarding linkages.

PMID- 15454888
TI  - Assessing hospital preparedness using an instrument based on the Mass Casualty
      Disaster Plan Checklist: results of a statewide survey.
AB  - BACKGROUND: Hospitals would play a critical role in a weapon of mass destruction
      (WMD) event. The purpose of this study is to assess preparedness for mass
      casualty events in short-term and long-term hospitals in Kentucky. METHODS: All
      short-term and long-term hospitals in Kentucky were surveyed using an instrument
      based on the Mass Casualty Disaster Plan Checklist and a brief supplemental
      bioterrorism preparedness questionnaire based on a checklist developed for the
      Agency for Healthcare Research and Quality. RESULTS: Responses were received from
      116 of the 118 (98%) hospitals surveyed. Hospitals reported surge capacity equal
      to 27% of licensed beds, and virtually all respondents were engaged in planning
      for weapons of mass destruction events. However, advanced planning and
      preparation were less common. Large regional differences were observed,
      especially in the area of pharmaceutical planning. Preparedness planning in
      general and pharmaceutical management planning in particular were more advanced
      in counties participating in the Metropolitan Medical Response System Program
      (MMRS). CONCLUSIONS: Hospital mass casualty preparedness efforts were in an early
      stage of development at the time of this survey, and some critical capabilities,
      such as isolation, decontamination, and syndromic surveillance were clearly
      underdeveloped. Preparedness planning was more advanced among hospitals located
      in MMRS counties.

PMID- 15454889
TI  - The effect of semipermeable dressings on smallpox vaccine site evolution.
AB  - BACKGROUND: Many hospital systems in the United States are contemplating the
      implementation of a smallpox vaccination program. The Centers for Disease Control
      and Prevention and other organizations recommend use of occlusive dressings over
      the vaccination site of health care workers in contact with patients. Minimal
      data are available on the impact of an occlusive dressing on the evolution of the
      vaccinia inoculation site. METHODS: We conducted a prospective observational
      study in which subjects were instructed to cover their vaccination site with
      either a semipermeable dressing over gauze or gauze alone. We recorded the
      duration of semipermeable dressing use and parameters pertaining to vaccination
      site evolution, to include time until scab separation. RESULTS: The increased use
      of a semipermeable dressing is associated with increased time until scab
      separation (n = 41, r =.48, P =.001 by regression analysis). This analysis
      predicts a 9-day difference in time until scab separation between patients that
      wore semipermeable dressings 100% of the time versus not at all. No significant
      correlation was observed between semipermeable dressing use and size of maximum
      erythema, time until maximum erythema, size of erythema on day 6 or 8, nor time
      until pustule formation. CONCLUSION: Semipermeable dressing use appears to
      prolong the time until scab separation and possibly the duration of infectivity
      and risk of secondary transmission. Health care organizations may wish to
      consider this information when instituting a smallpox vaccination program.

PMID- 15454891
TI  - Impact of FDA policy change on the reuse of single-use medical devices in
      Michigan hospitals.
AB  - BACKGROUND: Reuse of single-use devices (SUDs) was a common practice in many
      health care centers in the United States. In August 2000, the FDA presented a
      guidance document indicating their policy change that meant the FDA would
      regulate centers that reprocess SUDs. OBJECTIVE: Our objective was to survey
      Michigan health care centers to determine the level of action that has been taken
      regarding this policy change and determine whether there has been a shift in the
      extent of reuse of SUDs. METHODS: We developed a telephone survey tool and
      contacted the infection control personnel in the 54 Michigan hospitals that had
      more than 200 beds. RESULTS: The response rate to the telephone survey was 48 of
      54 (89%). Prior to the FDA policy change, 46%, 17%, and 37% performed on-site,
      third-party, or no reprocessing of SUDs, respectively. Currently, 21%, 35%, and
      44% performed on-site, third-party, or no SUD reuse, respectively. The major
      shift has been to utilization of third-party reprocessors as opposed to stopping
      reuse of SUDs. In the 27 centers that currently reprocess SUDs, the most common
      items included the following: compression sleeves, 13 of 27; pulse oximeters, 8
      of 27; PTCA cardiovascular catheters, 7 of 27; and biopsy forceps, 5 of 27. There
      were 61% (11/18) that resterilized open but unused SUDs with an equal split
      between on-site versus third-party resterilization. There were 3 sites that
      stopped reprocessing SUDs completely as a result of the FDA policy change and 4
      that previously did not reprocess SUDs that started using a third-party
      reprocessor. CONCLUSIONS: The FDA policy change has impacted how SUD reprocessing
      is being performed in Michigan. Few centers (1/48) reprocessing any high or
      medium-risk SUDs on-site at the time of the survey. There has been little overall
      reduction in SUD reprocessing, but there has been a shift to use of third-party
      reprocessors.

PMID- 15454892
TI  - Direct costs of multidrug-resistant Acinetobacter baumannii in the burn unit of a
      public teaching hospital.
AB  - We conducted a case-control study to determine the attributable direct costs of
      multidrug-resistant Acinetobacter baumannii (MDRAB) in the burn unit of a public
      teaching hospital. The mean total hospital cost of patients who acquired MDRAB
      was 98,575 dollars higher than that of control patients who had identical burn
      severity of illness indices ( P <.01). These data should help infection control
      practitioners and others determine the cost-effectiveness of specific
      interventions designed to control this emerging nosocomial pathogen.

PMID- 15454893
TI  - Respiratory protection against bioaerosols: literature review and research needs.
AB  - Research on respiratory protection against biologic agents is important to
      address major concerns such as occupational safety and terrorist attack. This
      review describes the literature on respiratory protection against bioaerosols and
      identifies research gaps. Respiratory protection is a complex field involving a
      number of factors, such as the efficiency of respirator filter material; face
      piece fitting; and maintenance, storage, and reuse of respirators. Several
      studies used nonpathogenic microorganisms having physical characteristics similar
      to that of Mycobacterium tuberculosis to analyze microbial penetration through
      respirators. Some studies showed that high-efficiency particulate air (HEPA) and
      N95 filters provided a higher level of protection than dust/mist (DM) and
      dust/mist/fume (DMF) filters. Flow rate and relative humidity appear to alter the
      level of penetration of microorganisms through respirator filters. The
      relationship between microbial penetration through respirator filters and the
      aerodynamic diameter, length, or other physical characteristics of microorganisms
      remains controversial. Whether reaerosolization of bioaerosol particles should be
      a concern is unclear, given the fact that one study has demonstrated significant
      reaerosolization of 1- to 5-microm particles loaded onto respirator filters.
      Respirator maintenance, storage, and decontamination are important factors to be
      considered when reusing respirators. The respiratory protection against biologic
      warfare agents such as anthrax in military and civilian situations is described.

PMID- 15454894
TI  - Prevalence of presumptive Bacillus anthracis in the human population examined by
      nasal swabs.
AB  - Routine cultures may reveal presumptive Bacillus anthracis microorganisms in
      human samples. Our study of 1336 individuals showed the probability of
      encountering presumptively positive cultures using routine microbiologic
      examination was approximately 0.4% (5 individuals) when nasal swabs were examined
      for the following characteristics indicative of Bacillus anthracis : nonhemolytic
      ground-glass colonies retaining their shape when manipulated, nonmotile in
      testing media, and microscopically revealing spore-forming gram-positive rods.
      Confirmatory tests revealed that those cultures were of Bacillus nonanthracis
      microorganisms. The probability appears significantly high to suggest a need for
      the confirmatory tests to be available at the community laboratories. In
      addition, our study confirmed the Gram's staining method does not kill all the
      spores of the spore-forming gram-positive rods, necessitating special safety
      requirements.

PMID- 15454895
TI  - Postdischarge surveillance: the impact on surgical site infection incidence in a
      Brazilian university hospital.
AB  - OBJECTIVE: This prospective cohort study was carried out in a surgical unit of a
      university hospital in Brazil. The purpose of the study was to determine the
      incidence of surgical site infection (SSI) in patients during hospitalization and
      after discharge from the hospital. METHOD: In a sample of 630 patients who
      underwent surgical procedures, association among diagnosis of SSI (in-hospital or
      postdischarge), class of the surgery (elective or emergency), hospitalization
      period, patient's clinical condition (American Society of Anesthesiologists [ASA]
      score), classification of surgical site, and duration of surgical procedure were
      verified. RESULTS: Fifty SSIs were diagnosed while the patients were still in the
      hospital, and 140 postdischarge. Hospitalization periods >5 days and worse
      clinical condition (ASA III) were associated with a higher SSI incidence.
      Classification of SSI was not correlated to the incidence of in-hospital SSI,
      except for clean surgeries. Surgical procedures of >5 hours duration were
      correlated to SSI during hospitalization, and procedures of >2 hours duration
      correlated to a postdischarge SSI. Most SSIs (73.7%) were diagnosed
      postdischarge. CONCLUSION: Results show a high incidence of postsurgical
      infection detected during postdischarge surveillance, which suggests the need for
      postdischarge follow-ups for surgical patients.

PMID- 15454896
TI  - Epidemiologic and clinical features of a sepsis caused by methicillin-resistant
      Staphylococcus epidermidis (MRSE) in a pediatric intensive care unit.

PMID- 15454897
TI  - Nosocomial Stenotrophomonas maltophilia cross-infection: three cases in newborns.
AB  - BACKGROUND: Increased nosocomial Stenotrophomonas maltophilia infection rates in
      newborns, especially in recent years, are a significant cause for concern. These
      cases are the second case group in the literature to have been identified as
      nosocomial cross-infection with S. maltophilia in neonates. OBJECTIVE: To
      investigate the clinical, microbiological, and epidemiologic features of the
      outbreak caused by S. maltophilia in the neonatal intensive care unit within a
      period of 7 days. METHODS: Three cases with nosocomial S. maltophilia infection
      considered to be the result of cross-transmission were prospectively analyzed.
      Arbitrarily primed polymerase chain reaction (AP-PCR) performed with M13 primer
      and pulsed-field gel electrophoresis (PFGE) of genomic DNA after digestion with
      XbaI were used to determine clonal relationship among the isolates. Results S.
      maltophilia was isolated from the blood cultures of all 3 patients. Molecular
      typing confirmed that the 3 cases were epidemiologically linked. CONCLUSIONS:
      Opportunistic pathogens such as S. maltophilia can lead to major problems in
      neonates. Molecular typing is helpful to improve effective control programs for
      preventing the spread of the infection.

PMID- 15454898
TI  - Inhalational phytochemicals as possible treatment for pulmonary tuberculosis: two
      case reports.

PMID- 15454899
TI  - Nosocomial bloodstream infection surveillance in trauma centers: the lack of
      uniform standards.

PMID- 15454900
TI  - Methicillin-resistant and -sensitive Staphylococcus aureus nasal colonization of
      insulin-dependent children with juvenile onset diabetes mellitus.

PMID- 15454901
TI  - Citrobacter koseri infection and abscess associated with Harrington rods.

PMID- 15454902
TI  - Klebsiella pneumoniae bacteremia associated with a Tesio hemodialysis catheter.

PMID- 15454903
TI  - Extra charge and extra length of hospital stay attributable to postcataract
      surgery endophthalmitis.

PMID- 15454904
TI  - Proof of alleged transmission of hepatitis C virus by a conjunctival blood
      splash.

PMID- 15454905
TI  - Body image changes associated with dual-chamber pacemaker insertion in women.
AB  - PURPOSE: The study's purpose was to examine body image changes in subjects
      participating in a long-term multicenter pacemaker trial. METHODS: At study
      closeout, 383 adults, all of whom had received a dual-chamber pacemaker,
      completed questionnaires evaluating what effect their pacemaker or pacemaker site
      and scar had on them or their spouses or significant others. RESULTS: Most
      reported that their pacemaker did not change the way they or their spouses or
      significant others felt about their body (73.2% and 93.5%, respectively). Most
      (87.1%) denied feeling differently because of the pacemaker site and scar. Most
      were not concerned how their clothes fit or about wearing a swimsuit (92.0% and
      90.7%, respectively). Women were more concerned about how the pacemaker site and
      scar made them feel about their body (P =.001), clothes fitting (P =.002), and
      wearing a swimsuit (P =.004). Men were more concerned with how their spouses or
      significant others perceived them postimplantation (P =.021). CONCLUSIONS: Most
      subjects did not express undue concern about changes in body image.

PMID- 15454907
TI  - Body position change and its effect on hemodynamic and metabolic status.
AB  - OBJECTIVE: The study's objective was to examine the effect of body position on
      oxygen consumption (Vo(2)) and hemodynamics. Although gravity-dependent
      hemodynamic and pulmonary consequences are well documented, less is known about
      the effect of body positions on VO(2) and hemodynamics, which is of importance in
      critical care. DESIGN: This was a quasi-experimental study. SETTING: The setting
      was a physiology laboratory controlled for noise and temperature (21 degrees C).
      SUBJECTS: Healthy, nonsmoking subjects were studied (n = 32; 18 women and 14 men
      aged 20 +/- 0.84 years [mean +/- SD]). Outcome measures After each subject was in
      each position of interest for 10 minutes, heart rate (HR), blood pressure (BP),
      rate pressure product (RPP) (an index of myocardial Vo(2) = HR x systolic BP),
      Vo(2). min. m(2), and arterial saturation (Spo(2)) were recorded for 10 minutes
      and averaged. All testing was conducted at midday. INTERVENTIONS: Five body
      positions used in the intensive care unit were standardized and included the
      following: sitting in a firm chair with feet supported (sitting), horizontal
      supine flat position (H-S), head-down (30 degrees ) supine flat position (HD-S),
      and right- and left-side lying (90 degrees ) positions (RSL and LSL,
      respectively). RESULTS: Generally, HR, BP, RPP, and Vo(2) were highest in the
      sitting position compared with the lying positions (P <.05) and lowest in the LSL
      position (P <.05). The H-S and HD-S positions tended to affect these variables
      comparably with the exception of HR, which was lowest in the H-S position and
      significantly lower in the HD-S positions (P <.05). Both systolic and diastolic
      BP were comparable in the sitting, H-S, and HD-S positions, and significantly
      lower in the RSL and LSL positions (P <.001). Similar to mean Vo(2), the mean RPP
      tended to be reduced across positions in the following sequence: sitting, HD-S, H
      S, RSL, and LSL. Spo(2) did not change across body positions. CONCLUSIONS: These
      results yield further insight into how the adverse and beneficial effects of body
      positioning as a therapeutic intervention may be mediated through gravitational
      stress and myocardial mechanics. Such an understanding is crucial when
      prescribing body positioning to enhance oxygenation in the patient in the
      intensive care unit and to minimize its adverse effects.

PMID- 15454908
TI  - Factors related to delay times in patients with suspected acute myocardial
      infarction.
AB  - OBJECTIVE: The study's objective was to describe symptoms, symptom management,
      and patient delay times in patients seeking treatment for suspected acute
      myocardial infarction (AMI), and to find explanatory factors influencing the
      decision time. METHOD: This is a descriptive survey study including 403 Swedish
      patients with a median age of 64 years with suspected AMI. RESULTS: Altogether,
      84% of the patients suspected that the symptoms emanated from the heart. Despite
      this fact, 59% delayed going to the hospital more than 1 hour after the onset of
      symptoms. In the multiple regression analysis, a "dull pain," the patients'
      belief that it was nothing serious, and contact with the general practitioner
      were associated with prolonged delay. The decision to contact the emergency
      service shortened the delay time. CONCLUSIONS: The patient's subjective feeling
      of the severity of symptoms is an important predictor for delay times. There is
      still a need for public awareness of the appropriate responses to AMI symptoms,
      that is, to call for an ambulance instead of contacting the general practitioner.

PMID- 15454909
TI  - Short-term outcomes and their predictors for patients hospitalized with community
      acquired pneumonia.
AB  - PURPOSE: This study of patients who were hospitalized with pneumonia describes 4
      short-term outcomes and the relative value of 4 variables for predicting the
      outcomes. METHOD: We prospectively documented 4 short-term outcomes (hospital
      length of stay, discharge location, death, 30-day readmission) among 213 adults
      (mean age = 72.5 years) with pneumonia who were admitted to the hospital.
      Relationships between the Pneumonia Severity Index (PSI), preadmission walking,
      malnutrition, grip strength, and outcomes were examined with correlations and
      multiple logistic regression. RESULTS: The mean (SD) hospital stay was 8.8 (10.4)
      days. Many patients (51.6%) were not discharged to their homes; 13.6% died during
      admission or within 30 days of discharge. Of 205 patients discharged alive, 23.9%
      were readmitted within 30 days. All predictor variables correlated significantly
      with length of stay, discharge, and death. Except for grip strength, all
      predictor variables correlated significantly with readmission. Regression showed
      that the PSI contributed significantly to the prediction of all outcomes but that
      other variables also contributed (R(2) =.099 [readmitted] to.484 [discharged to
      home]). CONCLUSIONS: Because malnutrition and physical performance measures
      independently predicted or added to the PSI's prediction of untoward outcomes,
      the measures merit inclusion when assessing patients with pneumonia.

PMID- 15454910
TI  - Patients' reports of health care practitioner interventions that are related to
      communication during mechanical ventilation.
AB  - BACKGROUND: The literature supports nursing interventions to maximize
      communication in mechanically ventilated patients, yet limited research exists on
      patients' perceptions of the helpfulness of health care practitioner
      interventions to enhance communication. In addition, the level of frustration
      experienced by these patients has not been reported. Thus, further research is
      necessary to examine patients' perspectives of the helpfulness of health care
      practitioner interventions that enhance communication of the mechanically
      ventilated patient. OBJECTIVES: This study describes the level of frustration
      experienced by mechanically ventilated patients and ascertains the helpfulness of
      methods used by health care practitioners to meet the communication needs of the
      mechanically ventilated patient. METHODS: A total of 29 critically ill patients,
      extubated within the last 72 hours, were included in this descriptive study using
      qualitative and quantitative methods. Subjects participated in an average 30
      minute audiotaped interview session consisting of questions pertinent to their
      perceived level of frustration in communicating and the interventions
      practitioners used to meet their communication needs. Transcripts were analyzed
      by question and for overall themes. RESULTS: It was found that 62% of patients (n
      = 18) reported a high level of frustration in communicating their needs while
      being mechanically ventilated. There was no significant difference between the
      duration of intubation and the level of frustration (Spearman r =.109, P =.573)
      or between the diagnosis and the level of frustration (P =.932). Patients who
      received anxiolytics (n = 23, 79% of the sample) had a lower level of frustration
      (mean 3.26) than those who did not receive anxiolytics (n = 6, 21% of the sample,
      mean 4.33). This difference trended toward significance (P =.084). Patients cited
      health care practitioner behaviors, characteristics, and attributes that both
      facilitated communication (kind, informative, and physically present at the
      bedside) and impeded their ability to communicate (mechanical, inattentive, and
      "absent" from the bedside). Patients reported problems and stresses associated
      with communication difficulties that can be alleviated by the health care
      practitioner. CONCLUSIONS: Mechanically ventilated patients experience a high
      level of frustration when communicating their needs, and health care providers
      have a significant impact on the mechanically ventilated patient's experience.
      Further research is needed to explore and measure methods of facilitating
      communication that increase patient satisfaction, reduce patient anxiety, and
      obtain optimal pain management.

PMID- 15454911
TI  - Wound care pain in hospitalized adult patients.
AB  - BACKGROUND: Wound care (WC) is an important part of treatment for hospitalized
      patients with wounds. There is a paucity of data about the type or amount of pain
      patients experience during WC. OBJECTIVES: The purpose of this study is to
      describe patients' (n = 412) WC-related pain perceptions and responses, examine
      the relationships between patients' WC pain and demographic variables, and
      describe the distress associated with WC. METHODS: A repeated-measures design was
      used to examine pain before, during, and after WC in hospitalized patients (n =
      412) with wounds healing by secondary intention. RESULTS: Pain intensity was
      greatest during WC. It was most frequently described as tender, sharp, stinging,
      aching, and stabbing. Behaviors that occurred most often were no verbal response,
      no body movement, grimace, and complaints of pain. There were no differences in
      pain between genders. Nonwhites had significantly greater WC pain than whites.
      Pain during the procedure was the same in younger and older patients, and
      procedural distress was mild. CONCLUSION: Patients experience pain and distress
      with WC. Some behaviors and words consistently describe WC pain. Further work is
      warranted to refine pain assessment and management in patients undergoing WC
      procedures.

PMID- 15454912
TI  - Investigation of sudden death from Mycobacterium tuberculosis in a foreign-born
      worker at a resort hotel.
AB  - A 60 year-old man born in Central America died suddenly in the hallway of his
      residence on the grounds of a resort hotel where he worked as a dishwasher. The
      dishwashing station was in a large, poorly ventilated area where a substantial
      number of food service workers (cooks, wait staff, bus persons, dishwashers,
      supervisors, etc.) shared air space with the index patient. Several social
      contacts of the patient reported that he had been coughing for many months before
      his death. The County Department Of Health conducted a contact investigation,
      which identified 171 individuals in need of follow-up. Thirty-six percent of
      those tested in the first round were tuberculin skin test-positive; a second
      round of testing yielded a 15% (8 of 52) conversion rate.

PMID- 15454913
TI  - Pacemaker pause.

PMID- 15454914
TI  - Xanthogranulomatous pyelonephritis complicated by psoas abscess.
AB  - Xanthogranulomatous pyelonephritis is an unusual variant of chronic
      pyelonephritis. Xanthogranulomatous pyelonephritis is associated with urinary
      calculi, urinary tract obstruction, and invasion of the renal parenchyma.
      Pathologically, xanthogranulomatous pyelonephritis consists of a yellow (xantho)
      colored infiltrate in renal tissue with granulomatous formation.
      Xanthogranulomatous pyelonephritis may be distinguished from chronic
      pyelonephritis by renal size. Typically, the kidneys are enlarged in
      xanthogranulomatous pyelonephritis and are small/shrunken with chronic
      pyelonephritis. The diagnosis of xanthogranulomatous pyelonephritis is made by
      abdominal computed tomography scanning showing the characteristic "bear paw"
      sign, or findings typical for xanthogranulomatous pyelonephritis, eg, multiple
      hypo dense areas with ring-enhancing lesions. The definitive treatment for
      xanthogranulomatous pyelonephritis is antimicrobial therapy and nephrectomy. We
      present a case of xanthogranulomatous pyelonephritis complicated by psoas
      abscess.

PMID- 15454915
TI  - Preliminary evidence of the combined benefit of short-term effects of exercise
      and music on cognitive performance.

PMID- 15454918
TI  - Toll bridges.

PMID- 15454919
TI  - The interface between innate and adaptive immunity.
AB  - This focus analyzes some of the ways the innate immune system influences adaptive
      immune responses. Here the main principles and themes that govern this intricate
      relationship are discussed.

PMID- 15454920
TI  - Toll-like receptors in the pathogenesis of human disease.
AB  - Members of the Toll-like receptor (TLR) family are key regulators of both innate
      and adaptive immune responses. The function of TLRs in various human diseases has
      been investigated by comparison of the incidence of disease among people having
      different polymorphisms in genes that participate in TLR signaling. These studies
      have shown that TLR function affects several diseases, including sepsis,
      immunodeficiencies, atherosclerosis and asthma. As this body of data grows, it
      will provide new insights into disease pathogenesis as well as valuable
      information on the merits of various therapeutic options.

PMID- 15454921
TI  - The complement system in regulation of adaptive immunity.
AB  - The serum complement system, which represents a chief component of innate
      immunity, not only participates in inflammation but also acts to enhance the
      adaptive immune response. Specific activation of complement via innate
      recognition proteins or secreted antibody releases cleavage products that
      interact with a wide range of cell surface receptors found on myeloid, lymphoid
      and stromal cells. This intricate interaction among complement activation
      products and cell surface receptors provides a basis for the regulation of both B
      and T cell responses. This review highlights fundamental events, explaining how
      complement links innate and adaptive immunity as well as describing more recent
      studies on how this large family of proteins functions locally in peripheral
      lymph nodes to enhance B and T cell responses.

PMID- 15454922
TI  - Toll-like receptor control of the adaptive immune responses.
AB  - Recognition of microbial infection and initiation of host defense responses is
      controlled by multiple mechanisms. Toll-like receptors (TLRs) have recently
      emerged as a key component of the innate immune system that detect microbial
      infection and trigger antimicrobial host defense responses. TLRs activate
      multiple steps in the inflammatory reactions that help to eliminate the invading
      pathogens and coordinate systemic defenses. In addition, TLRs control multiple
      dendritic cell functions and activate signals that are critically involved in the
      initiation of adaptive immune responses. Recent studies have provided important
      clues about the mechanisms of TLR-mediated control of adaptive immunity
      orchestrated by dendritic cell populations in distinct anatomical locations.

PMID- 15454923
TI  - Interplay of natural killer cells and their receptors with the adaptive immune
      response.
AB  - Although natural killer (NK) cells are defined as a component of the innate
      immune system, they exhibit certain features generally considered characteristic
      of the adaptive immune system. NK cells also participate directly in adaptive
      immune responses, mainly by interacting with dendritic cells. Such interactions
      can positively or negatively regulate dendritic cell activity. Reciprocally,
      dendritic cells regulate NK cell function. In addition, 'NK receptors' are
      frequently expressed by T cells and can directly regulate the functions of these
      cells. In these distinct ways, NK cells and their receptors influence the
      adaptive immune response.

PMID- 15454925
TI  - Cultures and identities.

PMID- 15454926
TI  - RAPL: taking the Rap in immunity.

PMID- 15454927
TI  - Unmasking connections in transmembrane immune signaling.

PMID- 15454928
TI  - DUBbing down innate immunity.

PMID- 15454929
TI  - A polarizing situation.

PMID- 15454931
TI  - 'Good citizenship' or good business?

PMID- 15454932
TI  - The case for a global human genome epidemiology initiative.

PMID- 15454933
TI  - Phylogenetic validation of horizontal gene transfer?

PMID- 15454934
TI  - The use of genome annotation data and its impact on biological conclusions.

PMID- 15454936
TI  - Tracing microRNA patterns in mice.

PMID- 15454937
TI  - How to make an ape brain.

PMID- 15454938
TI  - Shifting insulator boundaries.

PMID- 15454939
TI  - Linking pathways in colorectal cancer.

PMID- 15454942
TI  - The use of pedigree, sib-pair and association studies of common diseases for
      genetic mapping and epidemiology.
AB  - Efforts to identify gene variants associated with susceptibility to common
      diseases use three approaches: pedigree and affected sib-pair linkage studies and
      association studies of population samples. The different aims of these study
      designs reflect their derivation from biological versus epidemiological
      traditions. Similar principles regarding determination of the evidence levels
      required to consider the results statistically significant apply to both linkage
      and association studies, however. Such determination requires explicit attention
      to the prior probability of particular findings, as well as appropriate
      correction for multiple comparisons. For most common diseases, increasing the
      sample size in a study is a crucial step in achieving statistically significant
      genetic mapping results. Recent studies suggest that the technology and
      statistical methodology will soon be available to make well-powered studies
      feasible using any of these approaches.

PMID- 15454946
TI  - Primary unilateral pulmonary hypoplasia: neonate through early childhood - case
      report, radiographic diagnosis and review of the literature.
AB  - Unilateral pulmonary hypoplasia is a rare cause of respiratory distress in the
      neonate. It is usually secondary to other causes such as diaphragmatic hernia. We
      present a case of a newborn with primary hypoplasia of the right upper lobe who
      was later found to also have tracheobronchomalacia. We describe the clinical
      course through early childhood.

PMID- 15454947
TI  - Dislodgeable foliar residues are lognormally distributed for agricultural re
      entry studies.
AB  - The Agricultural Reentry Task Force (ARTF) conducted a study to determine if
      dislodgeable foliar residues (DFR) are either normally or lognormally
      distributed. This is important because the data are used with worker exposure
      data, which generally appear to be lognormally distributed, to calculate transfer
      coefficients that will be used to assess farm worker re-entry exposure. Two
      chemicals were used for this study. Carbaryl, a moderately water-soluble
      chemical, was applied to cabbage at a rate of 2.0 lbs active ingredient/acre (lb
      ai/A), while methomyl, a highly water soluble chemical, was applied to cabbage at
      a rate of 0.9 lb ai/A. The residues were dislodged following an ARTF standardized
      procedure of collecting leaf punches and shaking in a solution of 0.01% Aerosol
      OT 75. A total of 28 samples were analyzed for each chemical. The mean+/-SD
      residue of the carbaryl samples was higher than that for methomyl (511+/-196 and
      170+/-71 mug per sample, respectively). However, several types of statistical
      analyses of the data indicated that, for both chemicals, the residues are
      lognormally distributed.

PMID- 15454948
TI  - Population differentiation within and among Asian elephant (Elephas maximus)
      populations in southern India.
AB  - Southern India, one of the last strongholds of the endangered Asian elephant
      (Elephas maximus), harbours about one-fifth of the global population. We present
      here the first population genetic study of free-ranging Asian elephants,
      examining within- and among-population differentiation by analysing mitochondrial
      DNA (mtDNA) and nuclear microsatellite DNA differentiation across the Nilgiris
      Eastern Ghats, Anamalai, and Periyar elephant reserves of southern India. Low
      mtDNA diversity and 'normal' microsatellite diversity were observed.
      Surprisingly, the Nilgiri population, which is the world's single largest Asian
      elephant population, had only one mtDNA haplotype and lower microsatellite
      diversity than the two other smaller populations examined. There was almost no
      mtDNA or microsatellite differentiation among localities within the Nilgiris, an
      area of about 15,000 km2. This suggests extensive gene flow in the past, which is
      compatible with the home ranges of several hundred square kilometres of elephants
      in southern India. Conversely, the Nilgiri population is genetically distinct at
      both mitochondrial and microsatellite markers from the two more southerly
      populations, Anamalai and Periyar, which in turn are not genetically
      differentiated from each other. The more southerly populations are separated from
      the Nilgiris by only a 40-km-wide stretch across a gap in the Western Ghats
      mountain range. These results variably indicate the importance of population
      bottlenecks, social organization, and biogeographic barriers in shaping the
      distribution of genetic variation among Asian elephant populations in southern
      India.

PMID- 15454949
TI  - Identification and mode of action of self-compatibility loci in Lolium perenne L.
AB  - The two-locus gametophytic incompatibility system in perennial ryegrass (Lolium
      perenne L.) is not always fully effective: obligate selfing of plants sieves self
      compatible pollen mutants, and self-fertility becomes fixed in subsequent
      generations. Self-compatibility (SC) was investigated in an F2 family. In vitro
      self-pollinations were analysed and recorded and plants were classified as being
      either partially or fully compatible. Distorted segregation ratios of markers on
      linkage group (LG) 5 were found, which indicate the possible presence of a
      gametophytic SC locus. Interval linkage analysis of pollen compatibility after
      selfing confirmed that this distortion was due to a locus (T) analogous to the S5
      locus of rye. However, even though markers in this region were, on average, less
      than 1 cM apart, the minimum number of plants possessing the unfavoured allele
      was never less than 6% for any marker locus. We proved that this was because of
      the presence of another SC locus, exhibiting gametophytic selection, segregating
      in this population and identified by interval mapping analysis of compatibility
      classes of in vitro self-pollinations. This locus was located on LG1, and
      probably corresponds to the S locus. We show that the T locus, a relic of a
      multilocus system, functions through interaction with the S locus: F2 segregation
      of incompatibility phenotypes and linked markers demonstrated that the S/t pollen
      genotype combination, expected to be compatible on selfing, was sometimes
      incompatible. Further evidence is presented to show that this interaction must be
      dependent on yet another locus located on LG2. A prime candidate would be the Z
      incompatibility locus.

PMID- 15454951
TI  - Retroviral vectors: new applications for an old tool.
AB  - Retroviral vectors (RVs) have been used for stable gene transfer into mammalian
      cells for more than 20 years. The most popular RVs are those derived from the
      Moloney murine leukaemia virus (MoMLV). One of their main limitations is their
      inability to transduce noncycling cells. However, they have a relatively simple
      genome and structure, are easy to use, and are relatively safe for in vivo
      applications. For the last two decades, the artificial evolution of RVs has
      paralleled evolution in their applications, which now include those as diverse as
      the generation of transgenic animals, the stable delivery of small interfering
      RNA (siRNA) and gene therapy clinical trials. Recent reports of two successful
      gene therapy clinical trials in patients with severe immunodeficiency disease in
      France and Italy, and the development of T-cell acute leukaemia in two of 10
      children participating in one of these clinical trials, demonstrate the great
      potential of RVs, but also some potential risks which may be intrinsically
      associated with their use. Basic aspects of RVs and vector production were
      reviewed in detail in a previous supplement of this journal. This article will
      first summarize some general aspects of retroviruses and RVs. Thereafter, recent
      developments in gene therapy using RVs, novel applications such as stable RNA
      interference and some other recent issues related to retroviral integration,
      including clonality studies after haematopoietic stem cell transplantation,
      retroviral tagging and insertional oncogenesis will be discussed.

PMID- 15454952
TI  - Immune responses to gene therapy vectors: influence on vector function and
      effector mechanisms.
AB  - Circumventing the immune response to the vector is a major challenge with all
      vector types. Viral vectors are the most likely to induce an immune response,
      especially those, like adenovirus and AAV, which express immunogenic epitopes
      within the organism. The first immune response occurring after vector transfer
      emerges from the innate immune system, mainly consisting in a rapid (few hours)
      inflammatory cytokines and chemokines secretion around the administration site.
      This reaction is high with adenoviral vectors and almost null with AAV. It is
      noteworthy that plasmid DNA vectors, because of CpG stimulatory islets, also
      stimulate the innate immunity via the stimulation of TLR receptors on leukocytes.
      Specific immune response leading to antibodies production and T lymphocytes
      activation also occurs within a few days after vector introduction. Capsid
      antigens are mostly responsible for specific immunity toward adenoviruses, and
      are also involved in the response against AAV. In the former case only, however,
      viral gene-encoded proteins can also be immunogenic. The pre-existing humoral
      immunity coming from early infections with wild-type AAV or adenovirus can
      prevent efficient gene transfer with the corresponding vectors. In all cases,
      some parameters like route of administration, dose, or promoter type have been
      extensively described as critical factors influencing vector immunity. Strategies
      to fight against vector-induced immunity can come from the immunology field,
      since tolerance induction or immunosuppression are a possibility. Alterations to
      vector structure have also been extensively performed to circumvent the immune
      system and thus enhance gene transfer efficiency and safety.

PMID- 15454953
TI  - Gene transfer approaches in cancer immunotherapy.
AB  - The idea of enhancing or establishing effective immune response against
      endogenously developed tumor cells is not novel. More than a hundred years ago,
      bacterial components were used to develop antitumor immune response. Later, when
      a number of immune system-effecting cytokines had been discovered, they were used
      for systemic treatment of cancer patients. However, systemic treatment often
      resulted in even negative outcome. Recent developments of genetic approaches of
      cell modifications allowed developing of modern techniques of targeted tumor cell
      elimination. In the present paper, we review modern trends of the antitumor
      response enhancement based on immunoregulatory gene transfer into different cell
      types both in vivo and in vitro. Almost all these approaches are based on the
      activation of the adaptive arm of the immune system in response to tumor cells.
      However, recent studies indicate that the innate arm of the immune system, as
      well as adaptive arm, is involved in tumor suppression. The innate immune system
      uses nonrearranging germline receptors, which could trigger cellular effector
      responses that are conditional (or instructive) to the subsequent adaptive immune
      response. Last years' viewpoints on 'self' and 'non-self' recognition and primary
      induction of the immune response have changed. The key role of lymphocytes is
      pathogen recognition and, following immune response induction, switched on the
      central role of dendritic cells in 'non-self' recognition and induction of both
      innate and adaptive responses. Moreover, innate response is supposed to be an
      essential starting point in induction of successful and effective acquired
      response. Most cancer vaccines do not have 'non-self' marks presentation due to
      their endogenous origin, thus lacking their effectiveness in the induction of the
      specific long-lasting immune response. Taking this point into consideration, we
      can conclude that to make cancer vaccine more effective we have to present tumor
      antigens, together with the molecules that can potentially activate downstream
      'non-self' recognition events not in parallel, but as a consequence of tumor
      antigen processing and presentation.

PMID- 15454954
TI  - Recombinant AAV-mediated gene transfer to the retina: gene therapy perspectives.
AB  - Retinal degenerative diseases such as retinal macular degeneration and retinitis
      pigmentosa constitute a broad group of diseases that all share one critical
      feature, the progressive apoptotic loss of cells in the retina. There is
      currently no effective treatment available by which the course of these disorders
      can be modified, and visual dysfunction often progresses to total blindness. Gene
      therapy represents an attractive approach to treating retinal degeneration
      because the eye is easily accessible and allows local application of therapeutic
      vectors with reduced risk of systemic effects. Furthermore, transgene expression
      within the retina and effects of treatments may be monitored by a variety of
      noninvasive examinations. An increasing number of strategies for molecular
      treatment of retinal disease rely on recombinant adeno-associated virus (rAAV) as
      a therapeutic gene delivery vector. Before rAAV-mediated gene therapy for retinal
      degeneration becomes a reality, there are a number of important requirements that
      include: (1) evaluation of different rAAV serotypes, (2) screening of vectors in
      large animals in order to ensure that they mediate safe and long-term gene
      expression, (3) appropriate regulation of therapeutic gene expression, (4)
      evaluation of vectors carrying a therapeutic gene in relevant animal models, (5)
      identification of suitable patients, and finally (6) manufacture of clinical
      grade vector. All these steps towards gene therapy are still being explored.
      Outcomes of these studies will be discussed in the order in which they occur,
      from vector studies to preclinical assessment of the therapeutic potential of
      rAAV in animal models of retinal degeneration.

PMID- 15454955
TI  - DNA electrotransfer: its principles and an updated review of its therapeutic
      applications.
AB  - The use of electric pulses to transfect all types of cells is well known and
      regularly used in vitro for bacteria and eukaryotic cells transformation.
      Electric pulses can also be delivered in vivo either transcutaneously or with
      electrodes in direct contact with the tissues. After injection of naked DNA in a
      tissue, appropriate local electric pulses can result in a very high expression of
      the transferred genes. This manuscript describes the evolution in the concepts
      and the various optimization steps that have led to the use of combinations of
      pulses that fit with the known roles of the electric pulses in DNA
      electrotransfer, namely cell electropermeabilization and DNA electrophoresis. A
      summary of the main applications published until now is also reported, restricted
      to the in vivo preclinical trials using therapeutic genes.

PMID- 15454956
TI  - Gene therapy for cystic fibrosis: an example for lung gene therapy.
AB  - Gene therapy is currently being evaluated for a wide range of acute and chronic
      lung diseases. The requirement of gene transfer into the individual cell types of
      the complex lung structure will very much depend on the target disease. Over the
      last decade, the gene therapy community has recognized that there is not even one
      vector that is good for all applications, but that the gene transfer agent has to
      be carefully chosen. Gene therapy is particularly attractive for diseases that
      currently do not have satisfactory treatment options and probably easier for
      monogenic disorders than for complex diseases. Cystic fibrosis (CF) fulfills
      these criteria and is therefore a good candidate for gene therapy-based
      treatment. This review will focus on CF as an example for lung gene therapy and
      discuss the progress made in this field over the last couple of years.

PMID- 15454957
TI  - Treatment of peripheral sensorineural hearing loss: gene therapy.
AB  - Noise, chemicals and genetic defects are all common causes of irreversible
      hearing loss, which at present have no cure. Gene therapy may soon be utilized in
      both the protection and the treatment of these exogenous and endogenous sources
      of hearing loss. Gene therapy technology is rapidly developing and the inner ear
      is a particularly feasible model for gene therapy. This review outlines our
      current understanding of the mechanisms behind deafness and prospects for
      treatment, discusses the inner ear model in detail and reviews the efforts that
      have been made in inner ear gene therapy. Finally, the proposed next steps will
      be discussed. The viral mediated delivery of neurotrophins and antioxidants
      offers imminent promise in preventing and treating exogenous hearing loss and
      improving cochlear implant therapy.

PMID- 15454958
TI  - Current approaches and perspectives in human keratinocyte-based gene therapies.
AB  - Inherited and acquired disorders are liable to treatment with somatic gene
      therapy. The skin, and in particular epidermal cells, are particularly suited to
      genetic manipulation and follow-up of therapeutic effects. Cutaneous gene therapy
      may be effective for skin defects and systemic abnormalities. The robust basic
      and preclinical data available today would support the application of
      keratinocyte-based gene therapy to patients.

PMID- 15454959
TI  - Use of animals in experimental research: an ethical dilemma?
AB  - Mankind has been using animals already for a long time for food, for transport
      and as companion. The use of animals in experimental research parallels the
      development of medicine, which had its roots in ancient Greece (Aristotle,
      Hippocrate). With the Cartesian philosophy in the 17th century, experiments on
      animals could be performed without great moral problems. The discovery of
      anaesthetics and Darwin's publication on the Origin of Species, defending the
      biological similarities between man and animal, contributed to the increase of
      animal experimentation. The increasing demand for high standard animal models
      together with a critical view on the use of animals led to the development of
      Laboratory Animal Science in the 1950s with Russell and Burch's three R's of
      Replacement, Reduction and Refinement as guiding principles, a field that can be
      defined as a multidisciplinary branch of science, contributing to the quality of
      animal experiments and to the welfare of laboratory animals. The increased
      interest in and concern about animal welfare issues led to legislative
      regulations in many countries and the establishment of animal ethics committees.

PMID- 15454960
TI  - Lentivirus-mediated gene transfer to the respiratory epithelium: a promising
      approach to gene therapy of cystic fibrosis.
AB  - Gene therapy of cystic fibrosis (CF) lung disease needs highly efficient delivery
      and long-lasting complementation of the CFTR (cystic fibrosis transmembrane
      conductance regulator) gene into the respiratory epithelium. The development of
      lentiviral vectors has been a recent advance in the field of gene transfer and
      therapy. These integrating vectors appear to be promising vehicles for gene
      delivery into respiratory epithelial cells by virtue of their ability to infect
      nondividing cells and mediate long-term persistence of transgene expression.
      Studies in human airway tissues and animal models have highlighted the
      possibility of achieving gene expression by lentiviral vectors, which outlasted
      the normal lifespan of the respiratory epithelium, indicating targeting of a
      'stem cell' compartment. Modification of the paracellular permeability and
      pseudotyping with heterologous envelopes are the strategies currently used to
      overcome the paucity of specific viral receptors on the apical surface of airway
      epithelial cells and to reach the basolateral surface receptors. Preclinical
      studies on CF mice, demonstrating complementation of the CF defect, offer hope
      that lentivirus gene therapy can be translated into an effective treatment of CF
      lung disease. Besides a direct targeting of the stem/progenitor niche(s) in the
      CF airways, an alternative approach may envision homing of hematopoietic stem
      cells engineered to express the CFTR gene by lentiviral vectors. In the context
      of lentivirus-mediated CFTR gene transfer to the CF airways, biosafety aspects
      should be of primary concern.

PMID- 15454961
TI  - Liver gene therapy: advances and hurdles.
AB  - Liver gene therapy is being developed as an alternative to orthotopic liver
      transplantation, which is the only effective therapy for many liver diseases. The
      liver has unique features that make it attractive for in vivo and ex vivo gene
      transfer. In vivo approach is far less invasive than ex vivo approach, although
      in most cases, host immune response directed against the transgene product and/or
      vector particles severely impairs the efficiency of gene transfer, and precludes
      long-term transgene expression after in vivo gene delivery. Ex vivo approach
      allows for an elective targeting of the hepatocytes, avoiding that the transgene
      be expressed in professional antigen-presenting, but is faced with the low in
      vitro proliferative ability of hepatocytes, and to the low in vivo liver
      repopulating ability of transplanted cells. In some specific situations where
      immune response was controlled or transplanted cells had a strong growth
      advantage over host hepatocytes, gene transfer resulted in long-term and complete
      correction of a liver genetic defect. In this review, we will outline the liver
      diseases that may benefit from gene therapy, the vector technology under
      investigation, the advances and the problems to be overcome.

PMID- 15454962
TI  - Optical imaging of in vivo gene expression: a critical assessment of the
      methodology and associated technologies.
AB  - Following and quantifying the expression of reporter gene expression in vivo is
      very important to monitor the expression of therapeutic genes in targeted tissues
      in disease models and/or to assess the effectiveness of systems of gene therapy
      delivery. Gene expression of luminescent or fluorescent proteins can be detected
      directly on living animals by simply observing the associated optical signals by
      means of a cooled charged-coupled device camera. More accurate resolution can be
      obtained with more sophisticated technologies. Time-course and quasi-quantitative
      monitoring of the expression can be obtained on a given animal and followed on a
      large time window. The present paper describes the physical and technological
      methodologies and associated problems of in vivo optical imaging. Several
      examples of in vivo detection of gene delivery are described.

PMID- 15454963
TI  - Fetal and neonatal gene therapy: benefits and pitfalls.
AB  - The current approaches to gene therapy of monogenetic diseases into mature
      organisms are confronted with several problems including the following: (1) the
      underlying genetic defect may have already caused irreversible pathological
      changes; (2) the level of sufficient protein expression to ameliorate or prevent
      the disease requires prohibitively large amounts of gene delivery vector; (3)
      adult tissues may be poorly infected by conventional vector systems dependent
      upon cellular proliferation for optimal infection, for example, oncoretrovirus
      vectors; (4) immune responses, either pre-existing or developing following vector
      delivery, may rapidly eliminate transgenic protein expression and prevent future
      effective intervention. Early gene transfer, in the neonatal or even fetal
      period, may overcome some or all of these obstacles. The mammalian fetus enjoys a
      uniquely protected environment in the womb, bathed in a biochemically and
      physically supportive fluid devoid of myriad extra-uterine pathogens. Strong
      physical and chemical barriers to infection might, perhaps, impede the frenetic
      cell division. The physical support and the biochemical support provided by the
      fetal-maternal placental interface may, therefore, minimize the onset of genetic
      diseases manifest early in life. The fetal organism must prepare itself for
      birth, but lacking a mature adaptive immune system may depend upon more
      primordial immune defences. It is the nature of these defences, and the
      vulnerabilities they protect, that are poorly understood in the context of gene
      therapy and might provide useful information for approaches to gene therapy in
      the young, as well as perhaps the mature organism.

PMID- 15454964
TI  - Gene transfer vector biodistribution: pivotal safety studies in clinical gene
      therapy development.
AB  - Techniques allowing for gene transfer vectors biodistribution investigation, in
      the frame of preclinical gene therapy development, are exposed. Emphasis is given
      on validation and test performance assessment. In the second part, specific gene
      vector distribution properties are reviewed (adenovirus, AAV, plasmid,
      retroviruses, herpes-derived vectors, germline transmission risks). The rationale
      for biodistribution by quantitative PCR, animal study and result interpretation
      is discussed. The importance and pivotal role of biodistribution study in gene
      transfer medicine development is shown through the determination of target organs
      for toxicity, germline transmission assessment and determination of risks of
      shedding and spreading of vectors in the gene transfer recipient and the
      environment.

PMID- 15454965
TI  - Recombinant adeno-associated viral (rAAV) vectors as therapeutic tools for
      Duchenne muscular dystrophy (DMD).
AB  - Duchenne muscular dystrophy (DMD) is a lethal genetic muscle disorder caused by
      recessive mutations in the dystrophin gene. The size of the gene (2.4 Mb) and
      mRNA (14 kb) in addition to immunogenicity problems and inefficient transduction
      of mature myofibres by currently available vector systems are formidable
      obstacles to the development of efficient gene therapy approaches. Adeno
      associated viral (AAV) vectors overcome many of the problems associated with
      other vector systems (nonpathogenicity and minimal immunogenicity, extensive cell
      and tissue tropism) but accommodate limited transgene capacity (<5 kb). As a
      result of these observations, a number of laboratories worldwide have engineered
      a series of microdystrophin cDNAs based on genotype-phenotype relationship in
      Duchenne (DMD) and Becker (BMD) dystrophic patients, and transgenic studies in
      mdx mice. Recent progress in characterization of AAV serotypes from various
      species has demonstrated that alternative AAV serotypes are far more efficient in
      transducing muscle than the traditionally used AAV2. This article summarizes the
      current progress in the field of recombinant adeno-associated viral (rAAV)
      delivery for DMD, including optimization of recombinant AAV-microdystrophin
      vector systems/cassettes targeting the skeletal and cardiac musculature.

PMID- 15454971
TI  - Maternal coffee drinking in pregnancy and risk of small for gestational age
      birth.
AB  - OBJECTIVE: We have analysed the association between coffee drinking before and
      during the three trimesters of pregnancy and risk of small for gestational age
      (SGA) birth. METHODS: Cases were 555 women who delivered SGA births (ie <10th
      percentile according Italian standard). The controls included 1966 women who gave
      birth at term (>/=37 weeks of gestation) to healthy infants of normal weight.
      RESULTS: In comparison with nondrinkers, the ORs for SGA birth were 1.3 (95%
      confidence interval, CI, 0.9-1.9) for consumption of four or more cups of
      coffee/day before pregnancy, and 1.2 (95% CI 0.8-1.8), 1.2 (95% CI 0.8-1.8) and
      0.9 (95% CI 0.6-1.4) for consumption of three or more cups of coffee/day during
      the first, second and third trimester of pregnancy, respectively. CONCLUSION:
      These findings were consistent in women who delivered preterm and at term births
      and were not affected by potential confounding such as smoking.

PMID- 15454972
TI  - Phylloquinone intake as a marker for coronary heart disease risk but not stroke
      in women.
AB  - OBJECTIVE: To examine the feasibility of using phylloquinone intake as a marker
      for coronary heart disease (CHD) and stroke risk in women. DESIGN AND SETTING:
      Nurses' Health Study, a prospective cohort study during 1984-2000. Dietary data
      were collected in 1984, 1986, 1990, and 1994 using a validated semiquantitative
      food frequency questionnaire. SUBJECTS: A total of 72 874 female nurses, aged 38
      65 y, without previously diagnosed angina, myocardial infarction (MI), stroke, or
      cancer at baseline. MAIN OUTCOME MEASURES: Incidence of nonfatal MI, CHD deaths,
      total CHD events, ischemic, and total strokes. RESULTS: There were 1679 CHD
      events (1201 nonfatal) and 1009 strokes (567 ischemic). After adjustment for age
      and lifestyle factors associated with cardiovascular disease risk, the
      multivariate relative risks (RR) (95% CI) of total CHD from the lowest to the
      highest quintile category of phylloquinone intake were 1 (reference), 0.80 (0.69
      0.94), 0.86 (0.74-1.00), 0.77 (0.66-0.99), and 0.79 (0.68-0.92), P for
      trend=0.01. Further adjustment for dietary intakes of saturated fat,
      polyunsaturated fat, trans fatty acids, eicosapentaenoic, and docosahexaenoic
      acids, cereal fiber, and folate attenuated the association (RR comparing extreme
      quintiles 0.84 [0.71-1.00], P for trend=0.12). Incidence rates of total or
      ischemic strokes were not associated with phylloquinone intake. CONCLUSION: The
      data suggest that high phylloquinone intake may be a marker for low CHD risk.
      Dietary and lifestyle patterns associated with phylloquinone intakes, rather than
      intake of the nutrient itself, might account for all or part of the weak
      association. .

PMID- 15454973
TI  - Central and total adiposity are lower in overweight and obese children with high
      cardiorespiratory fitness.
AB  - OBJECTIVE: To examine the influence of cardiorespiratory fitness on total and
      truncal fatness in children. It was hypothesised that high cardiorespiratory
      fitness would result in lower total and central obesity. DESIGN: Observational
      cohort study. SETTING: Primary and secondary schools in Athens, Greece. SUBJECTS:
      A total of 1362 healthy children aged 6-13 y (742 boys and 620 girls). METHODS:
      Anthropometric data (height, body mass, four skinfolds thickness) were collected
      and per cent body fat was calculated. Body mass index (BMI) sex- and age-specific
      cutoff points were used for overweight and obesity definition and children were
      placed in two groups: overweight/obese and nonoverweight. Cardiorespiratory
      fitness (CRF) was assessed with the endurance shuttle-run test. Participants were
      grouped into high (upper two quintiles) and low (lower two quintiles) CRF based
      on age and sex distributions. T-test and Mann-Whitney test were used for
      comparisons between fit and unfit children within each BMI category. RESULTS: Sum
      of skinfolds, subscapular and truncal skinfold thickness, BMI and per cent body
      fat were lower in overweight and obese youths with high CRF in comparison with
      youths at the same BMI category with low CRF (P<0.01). The beneficial effect of
      high CRF was also presented in nonoverweight children (P<0.01). The influence of
      CRF on body composition remained even after correcting body fatness for BMI.
      CONCLUSIONS: Central and total obesity were lower in overweight and obese
      children with high CRF. This is the first study to show that a high CRF may
      reduce the hazards of obesity in children.

PMID- 15454974
TI  - Long-term effect of a plant-based diet on magnesium status during pregnancy.
AB  - OBJECTIVE: To compare dietary magnesium intake and magnesium concentrations in
      serum, red blood cells (RBC) and urine during pregnancy of women habitually
      following a long-term plant-based diet and of women following an average Western
      (control) diet. DESIGN: Prospective study during pregnancy. SETTING: Giessen,
      Germany. SUBJECTS: Healthy pregnant women (n=108) in their 9-12th, 20-22nd and 36
      38th gestational week habitually following a plant-based diet for more than 3 y
      or an average Western diet. The vegetarians were subdivided into ovo-lacto
      vegetarians (n=27) and low-meat eaters (n=43). RESULTS: Significant higher
      dietary magnesium intakes were observed in pregnant women consuming a plant-based
      diet (508+/-14 mg/day for ovo-lacto vegetarians, P<0.001 and 504+/-11 mg/day for
      low-meat eaters, P<0.001) than in pregnant women consuming a control diet (412+/
      9 mg/day). Serum magnesium concentrations were similar in all diet groups whereas
      RBC magnesium was slightly higher in low-meat eaters than in controls (P=0.058).
      Urinary magnesium excretion was higher in ovo-lacto vegetarians (P=0.023),
      followed by low-meat eaters (P=0.017) when compared to the control group. During
      the third trimester of pregnancy, the frequency and the occurrence of calf cramps
      was lower in the plant-based diet group than in the control group (P=0.004 and
      0.008). CONCLUSIONS: Owing to a higher dietary magnesium intake confirmed by
      higher urinary magnesium excretion, habitual plant-based diets result in a
      slightly improved magnesium status during pregnancy and reduce the frequency of
      calf cramps during the third trimester of pregnancy compared to an average
      Western diet. Therefore, plant-based diets during pregnancy can be recommended
      with regard to magnesium supply.

PMID- 15454976
TI  - Spin.

PMID- 15454977
TI  - Open co-operation.

PMID- 15454978
TI  - Selection procedures.

PMID- 15454979
TI  - Nut and tobacco chewing.

PMID- 15454980
TI  - Tongue in cheek.

PMID- 15454981
TI  - Paternalism and tradition.

PMID- 15454989
TI  - Endodontics: Part 3. Treatment of endodontic emergencies.
AB  - The swift and correct diagnosis of emergency problems is essential when providing
      treatment, especially in a busy dental practice. A diagnosis must be made and
      appropriate treatment provided in usually just a few minutes. The sequence
      considered here encompasses problems presenting before, during and after dental
      treatment. Various diagnostic aids are considered, and some unusual presenting
      conditions discussed.

PMID- 15454990
TI  - Five mandibular incisors: an autosomal recessive trait?
AB  - A fifth mandibular incisor is a eumorphic supernumerary tooth and has rarely been
      described in the medical literature. We report here a large Lebanese
      consanguineous family where four individuals displayed five incisors in the
      anterior mandible. Such familial observation has not been previously described.
      The possibility of an autosomal recessive inheritance for this nonsyndromic trait
      is discussed.

PMID- 15454991
TI  - The advantages and disadvantages of running a clinical trial in general
      practices.
AB  - This paper reviews the experiences encountered in running a clinical trial on the
      use of a metal reinforced glass-ionomer cement in general dental practices. The
      practitioners were asked to place both the test material and amalgam in the same
      patient and to take impressions both at placement and at three recall intervals.
      Subsequently plaster casts were produced from these impressions. These were then
      assessed by three independent observers to provide evaluation of the relative
      wear of the two restoratives under evaluation. A commercial laboratory
      manufactured the models on which the three independent observers carried out the
      assessment of wear. Although the practitioners indicated they would be able to
      provide the number of restorations required in a relatively short period these
      expected numbers were never achieved. Despite recruitment of additional
      participants the trial never did achieve the number of restorations required. The
      performance of the metal reinforced glass ionomer appeared to vary dependent on
      the practitioner placing the filling. Questioning of the participants found that
      some participants were finishing the material using a method specifically
      contraindicated in the protocol for the trial, the directions supplied with the
      product, and in briefing sessions held prior to the trial. This implies that
      there can be major problems in undertaking clinical trials of this nature in the
      general dental service and has serious clinical implications for those
      contemplating this type of evaluation and for manufacturers introducing new
      products.

PMID- 15454992
TI  - Cutaneous facial sinus tract of denture-related aetiology? A case report.
AB  - A case is reported of a chronic facial sinus on the mandible. It is postulated
      that this was due to chronic mucosal trauma associated with a poorly adapted
      denture in a patient rendered immunosuppressed by poorly controlled type II
      diabetes. Previous treatment with antibiotics alone was unsuccessful. Healing was
      only achieved when antibiotics were combined with removal of the denture and
      improved diabetic control.

PMID- 15454999
TI  - Aesthetically objectionable fluorosis in the United Kingdom.
AB  - OBJECTIVES: A cross-sectional national survey to explore perceptions of dental
      fluorosis and to determine the proportion of people regarding fluorosis as
      aesthetically objectionable at differing levels of defect. METHODS: A survey
      using a multistage stratified random probability sample of 6,000 UK adult
      households. Face-to-face interviews were carried out using a structured
      questionnaire and photographs of different levels of dental fluorosis.
      Respondents were interviewed about the parameters of satisfaction, attractiveness
      and need for treatment for dental fluorosis. RESULTS: The proportion of
      respondents perceiving teeth as unattractive, unsatisfactory and requiring
      treatment increased with increasing severity of dental fluorosis. Using agreement
      between the three negative perceptions as a measure, 14% of the sample perceived
      mild dental fluorosis as aesthetically objectionable, 45% at moderate level and
      91% at severe levels. CONCLUSION: Negative perceptions of dental fluorosis were
      lower than reported previously. Three parameters were included in the approach to
      estimate aesthetically objectionable fluorosis which may provide a more realistic
      measure than those used previously. The nature of the index and the sample
      included suggest that findings of this survey provide a reasonable indicator of
      the likely impact of water fluoridation. Findings may have important implications
      for fluoridation policies in the United Kingdom and elsewhere.

PMID- 15455000
TI  - Patient expectations of emergency dental services: a qualitative interview study.
AB  - OBJECTIVE: To describe the expectations of walk-in patients seeking emergency
      dental care out-of-hours. BASIC DESIGN: Consecutive patients attending two
      emergency dental clinics at weekends were interviewed prior to seeing the
      dentist. The audio-recorded interview transcripts were analysed using the
      "framework" method of applied qualitative data analysis. SUBJECTS AND SETTING:
      Forty-four walk-in emergency dental patients at a community-based dental clinic
      and a dental hospital emergency clinic at the weekend. RESULTS: In addition to
      symptom relief, the main desired outcome for emergency dental patients may be
      informational and psychological--especially reassurance that the problem is not
      serious, and reduced uncertainty about the cause of the pain. In general,
      patients' stated expectations for specific treatments (such as antibiotics, or
      tooth extraction) were not absolute: rather, they implied these expectations were
      conditional upon the dentist deciding they were necessary. CONCLUSIONS: Emergency
      dental services, some of which are still dominantly treatment-focused, should
      reflect that many emergency dental attenders want advice and reassurance as much
      as relief from symptoms. This reinforces the importance of effective and
      sympathetic dentist-patient communication within emergency or out-of-hours
      consultations. It also implies that dentists' skills in listening, explaining and
      reassuring should be captured in any patient satisfaction or outcome measure
      designed for this patient group.

PMID- 15455001
TI  - The GKT diploma in dental sedation--a judgement.
AB  - AIMS AND OBJECTIVES: The use of sedation in the management of pain and anxiety
      for the provision of dental care is as vital to the dental profession as are
      windscreen wipers to a motor vehicle. Not for use on every patient or every
      occasion, but in times of need to wipe away the tears, and essential for
      effective work. Training in sedation techniques should be a part of the
      undergraduate curriculum, and postgraduate opportunities need to be developed to
      support this important aspect of care. This paper examines a particular training
      course provided within the Department of Sedation and Special Care Dentistry at
      GKT Dental Institute, King's College London, leading to the Diploma in Conscious
      Sedation for Dentistry (Dip.D.Sed). The aim of this study was to investigate what
      impact the course has had on the practice of sedation. Three objectives were
      defined: 1) Students' evaluation of the course; 2) Students' practice in sedation
      prior to and on completion of the course; 3) Students' involvement in sedation
      training of dentists or dental nurses following completion of the course. METHOD:
      Information was obtained by postal questionnaire from students who had attended
      the course since its inception in 1997 to 2000. RESULTS: 30 students completed
      and returned the questionnaire which represented a 100% response. There was an
      overall expression of satisfaction from students on the course content and the
      experience they had obtained. The range of experience was 70-100 treatment
      episodes over 40 clinical sessions. An increase in both the practice of sedation
      and the involvement in training (dental nurses and dentists) was also shown. The
      greatest clinical change was the increase in use of intravenous sedation by the
      students from the community dental service. CONCLUSION AND RECOMMENDATION: This
      study concluded that the objectives of the course had been achieved. The
      importance of providing training that enables the safe and effective provision of
      sedation within primary care as an operator sedationist was strengthened by this
      study. The value of an intermediate level between the two day section 63 course
      and the six month diploma course was suggested by students in this study. The
      development of a clinical attachment based on The Standard Course in Conscious
      Sedation was proposed as a possible option to fill the gap. The provision of
      postgraduate training in sedation is limited particularly in some areas of the
      UK. This problem should be addressed by increasing the opportunity for
      postgraduate training in sedation by dental schools and postgraduate deaneries.
      Work towards increasing the funding and opportunities for training in this
      important area of care needs to be undertaken.

PMID- 15455032
TI  - EGF signal propagation during C. elegans vulval development mediated by ROM-1
      rhomboid.
AB  - During Caenorhabditis elegans vulval development, the anchor cell (AC) in the
      somatic gonad secretes an epidermal growth factor (EGF) to activate the EGF
      receptor (EGFR) signaling pathway in the adjacent vulval precursor cells (VPCs).
      The inductive AC signal specifies the vulval fates of the three proximal VPCs
      P5.p, P6.p, and P7.p. The C. elegans Rhomboid homolog ROM-1 increases the range
      of EGF, allowing the inductive signal to reach the distal VPCs P3.p, P4.p and
      P8.p, which are further away from the AC. Surprisingly, ROM-1 functions in the
      signal-receiving VPCs rather than the signal-sending AC. This observation led to
      the discovery of an AC-independent activity of EGF in the VPCs that promotes
      vulval cell fate specification and depends on ROM-1. Of the two previously
      reported EGF splice variants, the longer one requires ROM-1 for its activity,
      while the shorter form acts independently of ROM-1. We present a model in which
      ROM-1 relays the inductive AC signal from the proximal to the distal VPCs by
      allowing the secretion of the LIN-3L splice variant. These results indicate that,
      in spite of their structural diversity, Rhomboid proteins play a conserved role
      in activating EGFR signaling in C. elegans, Drosophila, and possibly also in
      mammals.

PMID- 15455033
TI  - Developmental context determines latency of MYC-induced tumorigenesis.
AB  - One of the enigmas in tumor biology is that different types of cancers are
      prevalent in different age groups. One possible explanation is that the ability
      of a specific oncogene to cause tumorigenesis in a particular cell type depends
      on epigenetic parameters such as the developmental context. To address this
      hypothesis, we have used the tetracycline regulatory system to generate
      transgenic mice in which the expression of a c-MYC human transgene can be
      conditionally regulated in murine hepatocytes. MYC's ability to induce
      tumorigenesis was dependent upon developmental context. In embryonic and neonatal
      mice, MYC overexpression in the liver induced marked cell proliferation and
      immediate onset of neoplasia. In contrast, in adult mice MYC overexpression
      induced cell growth and DNA replication without mitotic cell division, and mice
      succumbed to neoplasia only after a prolonged latency. In adult hepatocytes, MYC
      activation failed to induce cell division, which was at least in part mediated
      through the activation of p53. Surprisingly, apoptosis is not a barrier to MYC
      inducing tumorigenesis. The ability of oncogenes to induce tumorigenesis may be
      generally restrained by developmentally specific mechanisms. Adult somatic cells
      have evolved mechanisms to prevent individual oncogenes from initiating cellular
      growth, DNA replication, and mitotic cellular division alone, thereby preventing
      any single genetic event from inducing tumorigenesis.

PMID- 15455034
TI  - Identification of Birds through DNA Barcodes.
AB  - Short DNA sequences from a standardized region of the genome provide a DNA
      barcode for identifying species. Compiling a public library of DNA barcodes
      linked to named specimens could provide a new master key for identifying species,
      one whose power will rise with increased taxon coverage and with faster, cheaper
      sequencing. Recent work suggests that sequence diversity in a 648-bp region of
      the mitochondrial gene, cytochrome c oxidase I (COI), might serve as a DNA
      barcode for the identification of animal species. This study tested the
      effectiveness of a COI barcode in discriminating bird species, one of the largest
      and best-studied vertebrate groups. We determined COI barcodes for 260 species of
      North American birds and found that distinguishing species was generally
      straightforward. All species had a different COI barcode(s), and the differences
      between closely related species were, on average, 18 times higher than the
      differences within species. Our results identified four probable new species of
      North American birds, suggesting that a global survey will lead to the
      recognition of many additional bird species. The finding of large COI sequence
      differences between, as compared to small differences within, species confirms
      the effectiveness of COI barcodes for the identification of bird species. This
      result plus those from other groups of animals imply that a standard screening
      threshold of sequence difference (10x average intraspecific difference) could
      speed the discovery of new animal species. The growing evidence for the
      effectiveness of DNA barcodes as a basis for species identification supports an
      international exercise that has recently begun to assemble a comprehensive
      library of COI sequences linked to named specimens.

PMID- 15455035
TI  - Effects of juvenile hormone and ecdysone on the timing of vitellogenin appearance
      in hemolymph of queen and worker pupae of Apis mellifera.
AB  - The caste-specific regulation of vitellogenin synthesis in the honeybee
      represents a problem with many yet unresolved details. We carried out experiments
      to determine when levels of vitellogenin are first detected in hemolymph of
      female castes of Apis mellifera, and whether juvenile hormone and ecdysteroids
      modulate this process. Vitellogenin levels were measured in hemolymph using
      immunological techniques. We show that in both castes the appearance of
      vitellogenin in the hemolymph occurs during the pupal period, but the timing was
      different in the queen and worker. Vitellogenin appears in queens during an early
      phase of cuticle pigmentation approximately 60h before eclosion, while in workers
      the appearance of vitellogenin is more delayed, initiating in the pharate adult
      stage, approximately 10h before eclosion. The timing of vitellogenin appearance
      in both castes coincides with a slight increase in endogenous levels of juvenile
      hormone that occurs at the end of pupal development. The correlation between
      these events was corroborated by topical application of juvenile hormone.
      Exogenous juvenile hormone advanced the timing of vitellogenin appearance in both
      castes, but caste-specific differences in timing were maintained. Injection of
      actinomycin D prevented the response to juvenile hormone. In contrast, queen and
      worker pupae that were treated with ecdysone showed a delay in the appearance of
      vitellogenin. These data suggest that queens and workers share a common control
      mechanism for the timing of vitellogenin synthesis, involving an increase in
      juvenile hormone titers in the presence of low levels of ecdysteroids.

PMID- 15455037
TI  - The nest as fortress: defensive behavior of Polybia emaciata, a mud-nesting
      eusocial wasp.
AB  - The swarm-founding wasp Polybia emaciata is unusual among eusocial Vespidae
      because it uses mud, rather than wood pulp, as its primary nest construction
      material. Polybia emaciata nests are more durable than similarly sized paper
      nests. We tested the hypothesis that the defensive behavior of this wasp may have
      been modified to take advantage of their strong nests in defense against
      vertebrate attacks. We simulated vertebrate disturbances by tapping on, and
      breathing in, P. emaciata nests and similarly sized P. occidentalis paper nests
      in the same location at the same time. Polybia emaciata responses to disturbance
      were qualitatively different from those of P. occidentalis. The latter exit the
      nest and attack, while P. emaciata workers typically fled or entered the nest,
      attacking only after repeated and extended disturbances. We conclude that durable
      nest material may permit predator avoidance behavior in P. emaciata. We compare
      the defensive responses of P. emaciata workers with those of other swarm-founding
      Vespidae, and discuss several selective forces that could cause the evolution of
      species variation in nest defense behavior.

PMID- 15455036
TI  - Substrate vibrations during acoustic signalling in the cicada Okanagana rimosa.
AB  - Males of the North American cicada Okanagana rimosa (Homoptera: Cicadidae,
      Tibicininae) emit loud airborne acoustic signals for intraspecific communication.
      Specialised vibratory signals could not be detected; however, the airborne signal
      induced substrate vibrations. Both auditory and vibratory spectra peak in the
      range from 7-10 kHz. Thus, the vibrations show similar frequency components to
      the sound spectrum within biologically relevant distances. These vibratory
      signals could be important as signals involved in mate localization and perhaps
      even as the context for the evolution of the ear in a group of parasitoid flies.

PMID- 15455038
TI  - Ninetis russellsmithi n. sp., an unusual new pholcid spider species from Malawi
      (Araneae: Pholcidae).
AB  - A new species Ninetis russellsmithi n. sp. is described from Malawi. It lacks the
      most prominent autapomorphy of pholcid spiders, the retrolateral projection of
      the cymbium (procursus). Biogeographically this species marks the first record
      for the genus in a 3000 km gap between its African congeners in Namibia and
      Tanzania.

PMID- 15455039
TI  - Behavioral responses of adult female tobacco hornworms, Manduca sexta, to
      hostplant volatiles change with age and mating status.
AB  - We present evidence for two behaviors influenced by intact, vegetative plant odor
      - upwind flight and abdomen curling - in female Manduca sexta and demonstrate the
      influence of the age and mating status of the moths on these behaviors. We
      compared the behavioral responses of laboratory-reared M. sexta. of discrete ages
      and physiological states (2,3, and 4 day old for virgin; 2 and 3 day old for
      mated) as individual moths flew upwind in a flight tunnel to a source of
      hostplant volatiles. We monitored odor-modulated flight and abdomen curling in
      the presence of volatiles released by potted hostplants. Mated 3 day old females
      exhibited the highest incidence of odor-modulated flight and abdomen curling.
      Similarly, as virgin moths aged, a greater percentage of the individuals
      displayed odor-modulated flight patterns and abdomen curling. In contrast,
      younger virgin moths exhibited high levels of abdomen curling only after contact
      with the plant.

PMID- 15455040
TI  - Zinc and Manduca sexta hemocyte functions.
AB  - Two metalloproteases have recently been linked to the immune response in
      Lepidoptera. In addition, zinc is highly important in many mammalian immune
      related functions. Because of these, we investigated the effect of zinc and two
      zinc-protease inhibitors on Manduca sexta hemocyte behavior in vitro.
      Plasmatocytes were significantly more elongated in Grace's medium supplemented
      with 100 micro m zinc chloride than in the absence of zinc. To test whether zinc
      dependent proteases were responsible for the increased length seen in the
      presence of zinc, we tested two zinc-protease inhibitors, phosphoramidon and
      bestatin. Each resulted in decreased plasmatocyte length compared to the control,
      but the distributions of lengths differed with each inhibitor. Each inhibitor
      also affected plasmatocyte network formation in vitro. This work suggests (1)
      that at least two different zinc proteases are involved in the cellular defense
      response of M. sexta, and (2) that zinc should be included in media used for in
      vitro studies of the immune response.

PMID- 15455041
TI  - Aedes aegypti ferritin heavy chain homologue: feeding of iron or blood influences
      message levels, lengths and subunit abundance.
AB  - Secreted ferritin in the mosquito, Aedes aegypti, has several subunits that are
      the products of at least two genes, one encoding a homologue of the vertebrate
      heavy chain (HCH) and the other the light chain homologue (LCH). Here we report
      the developmental and organ specific pattern of expression of the ferritin HCH
      messages and of both subunit types in control sugar-fed mosquitoes, in those
      exposed to high levels of dietary iron, and after blood feeding. When Northern
      blots were probed with a HCH cDNA, two bands were observed, representing at least
      two messages of different sizes that result from the choice of two different
      polyadenylation sites. Either raising mosquito larvae in an iron-enriched medium,
      or blood feeding adult female mosquitoes resulted in a marked increase in the HCH
      message level, particularly of the shorter message. Changes in the amount and
      length of messages and amount of ferritin subunits were studied over the life
      span of the mosquito and in different organs of female mosquitoes after blood
      feeding. The midgut of blood-fed insects is the main site of increased ferritin
      message synthesis. Ferritin protein levels also increase in midgut, fat body and
      hemolymph after blood feeding. Ferritin messages and subunits are synthesized in
      the ovaries and ferritin is found in the eggs. These observations are discussed
      in terms of translational and transcriptional control of ferritin synthesis and
      are compared to similar events in the regulation of Drosophila melanogaster
      ferritin.

PMID- 15455042
TI  - The protective nature of Chironomus luridus larval tubes against copper sulfate.
AB  - The objective of this study was to determine whether the tubes in which
      Chironomus larvae dwell protect them against chemical toxicants. A laboratory
      culture of an Israeli benthic midge, Chironomus luridus, was exposed to copper
      sulfate. Two conditions were tested in bioassay experiments: larvae within silt
      tubes and larvae without tubes. The non toxic, anionic, fluorescent dye,
      fluorescein, was used to examine the effect of sub-lethal copper sulfate
      concentrations on the permeability of cuticular, gill and gut epithelia of the
      chironomids. Increased cell permeability, which is the cause of cell damage, was
      reflected by an increase in fluorescence intensity. Following exposure to copper
      sulfate, higher fluorescence was found in different body compartments: midgut,
      hindgut, tracheal gills, fat body and muscles, and the Malpighian tubules. The
      effect was significantly higher in tube-free larvae when compared to silt tube
      dwelling larvae. We conclude that in addition to its other functions in feeding,
      respiration, and anti-predation shelter, the Chironomus luridus tube protects its
      inhabitant from toxins such as copper sulfate.

PMID- 15455043
TI  - Methods for maintaining insect cell cultures.
AB  - Insect cell cultures are now commonly used in insect physiology, developmental
      biology, pathology, and molecular biology. As the field has advanced from methods
      development to a standard procedure, so has the diversity of scientists using the
      technique. This paper describes methods that are effective for maintaining
      various insect cell lines. The procedures are differentiated between loosely or
      non-attached cell strains, attached cell strains, and strongly adherent cell
      strains.

PMID- 15455044
TI  - Purification and partial characterization of an entomopoxvirus (DLEPV) from a
      parasitic wasp of tephritid fruit flies.
AB  - An insect poxvirus [entomopoxvirus (EPV)] occurs in the poison gland apparatus of
      female Diachasmimorpha longicaudata, a parasitic wasp of the Caribbean fruit fly,
      Anastrepha suspensa and other tephritid fruit flies. The DlEPV virion is 250-300
      nm in diameter, has a "bumpy" appearance and a unipartite double stranded DNA
      genome of 290-300 kb. DlEPV DNA restriction fragment profiles differed from those
      reported for Amsacta moorei EPV (AmEPV) and Melanoplus sanguinipes EPV (MsEPV),
      the only two EPVs whose genomes have been sequenced, and from those reported for
      vaccinia (Vac), a vertebrate poxvirus (chordopoxvirus, ChPV). Blast search and
      ClustalW alignment of the amino acids deduced from the 2316 nucleotides of a
      DlEPV DNA fragment cloned from an EcoR1 genomic library revealed 75-78% homology
      with the putative DNA-directed RNA polymerases of AmEPV, MsEPV, and two ChPV
      homologs of the Vac J6R gene. Of the deduced 772 amino acids in the DlEPV
      sequence, 28.4% are conserved/substituted among the four poxviruses aligned,
      12.9% occur in at least one EPV, 6.5% in at least one ChPV, 3.1% in at least one
      EPV and one ChPV, and 49.1% occur only in DlEPV. Although the RI-36-1 fragment
      represents a portion of the gene, it contains nucleotides that encode the
      NADFDGDE consensus sequence of known DNA-directed RNA polymerases. Western blots
      using a mouse polyclonal anti-DlEPV serum recognized six major protein bands in
      combined fractions of sucrose-purified DlEPV, at least one band in homogenates of
      male and female wasps, and at least two bands in host hemolymph that contained
      DlEPV virions. A digoxigenin-labeled DlEPV genomic DNA probe recognized DNA in
      dot-blots of male and female wasps. These results confirm that DlEPV is a true
      EPV and probably a member of the Group C EPVs. Unlike other EPVs, DlEPV does not
      express the spheroidin protein. Since it also replicates in both the wasp and
      fly, members of two different insect Orders, DlEPV may represent a new EPV Group,
      or a subgroup of the Group C viruses.

PMID- 15455045
TI  - Ecdysteroid 7,9(11)-dien-6-ones as potential photoaffinity labels for ecdysteroid
      binding proteins.
AB  - Three ecdysteroid 7,9(11)-dien-7-ones (dacryhainansterone, 25
      hydroxydacryhainansterone and kaladasterone) were prepared by dehydration of the
      corresponding 11a-hydroxy ecdysteroids (ajugasterone C, turkesterone and
      muristerone A, respectively). The biological activities of the dienones in the
      Drosophila melanogaster B(II) cell bioassay, which reflect the affinity for the
      ecdysteroid receptor complex, showed that the dienones retain high biological
      activity. Irradiation at 350 nm of the ecdysteroid dienones (100 nM) with
      bacterially-expressed dipteran and lepidopteran ecdysteroid receptor proteins
      (DmEcR/DmUSP or CfEcR/CfUSP), followed by loading with [(3)H]ponasterone A
      revealed that irradiation of dacryhainansterone or kaladasterone resulted in
      blocking of >70% of the specific binding sites. Thus, ecdysteroid dienones show
      considerable potential as photoaffinity analogues for ecdysteroid binding
      proteins.

PMID- 15455046
TI  - The natural history of the arboreal ant, Crematogaster ashmeadi.
AB  - The arboreal ant, Crematogaster ashmeadi Emery (Hymenoptera: Formicidae), is the
      most dominant arboreal ant in the pine forests of the coastal plain of northern
      Florida. The majority of pine trees harbor a colony of these ants. The colonies
      inhabit multiple chambers abandoned by bark-mining caterpillars, especially those
      of the family Cossidae, in the outer bark of living pines. They also inhabit
      ground level termite galleries in the bark, often locating the queen in
      galleries. The density of chambers and ants is highest in the base of the tree
      and drops sharply with height on the trunk. Because chambers are formed in the
      inner layer of bark, they gradually move outward as more bark layers are laid
      down, eventually sloughing off the tree's outer surface. Chambers have a mean
      lifetime of about 25 yr. The abundant chambers in pine bark are excavated by a
      small population of caterpillars and accumulate over decades. Ant colonies also
      inhabit abandoned galleries of woodboring beetles in dead branches in the crowns
      of pines. Because newly mated queens found colonies in abandoned woodboring
      beetle galleries in the first dead branches that form on pine saplings, C.
      ashmeadi is dependent on cavities made by other insects throughout its life
      cycle, and does little if any excavation of its own. Mature colonies nest
      preferentially in chambers greater than 10 cm(2) in area, a relatively rare
      chamber size. In natural pine forests, this does not seem to limit the ant's
      populations. Founding queens contain about 50% fat and lose about half of their
      dry weight during the claustral period, converting approximately half of this
      lost weight into progeny. The claustral period is about 40 to 50 days at 27
      degrees C. Mature colonies contain several tens of thousands of workers (est. up
      to 80,000), and have a life expectancy of 10 to 15 years. Each colony occupies an
      entire tree, and sometimes two trees if they are close together. Within a colony,
      there is a single queen capable of laying up to 450 eggs/day during the warm
      season. Such queens weigh 12 to 18 mg, have 50 to 60 active ovarioles and 120 to
      600 vitellogenic oocytes in their ovaries. Mature colonies begin producing sexual
      brood in late April or early May. Sexual adults are present from late May through
      June. Mating flights commence in June and most sexuals have left their natal
      nests by late July. Female sexuals are an especially large investment; the
      energetic content of a single, flight-ready female sexual is almost 20 times that
      of a worker. The newly mated queen sequesters a mean of 2.64 x 10(6) sperm in her
      spermatheca, a supply that should last her for 16 years at the observed
      reproductive rates.

PMID- 15455047
TI  - The presence of the coffee berry borer, Hypothenemus hampei, in Puerto Rico: fact
      or fiction?

PMID- 15455048
TI  - Male coercion and convenience polyandry in a calopterygid damselfly.
AB  - Copulation in odonates requires female cooperation because females must raise
      their abdomen to allow intromission. Nevertheless in Calopteryx haemorrhoidalis
      haemorrhoidalis (Odonata) males commonly grasp ovipositing females and apparently
      force copulations. This has been interpreted as a consequence of extreme
      population density and male-male competition. We studied this behavior at two
      sites on a river that had different densities over three years. As predicted, at
      high densities most matings were forced (i.e. not preceded by courtship), but at
      low density most were preceded by courtship. Courtship matings were shorter at
      high density, but density did not affect the duration of forced matings. Females
      cooperated in forced matings even if they had very few mature eggs. Furthermore,
      females mated more times if they experienced higher male harassment during
      oviposition, and at low density second and subsequent matings were more likely to
      be forced. We interpret these results to mean that females engage in "convenience
      polyandry", because they gain more by accepting copulation than by resisting
      males. The results also suggest that females might trade copulations for male
      protection, because under extreme population density harassment by males is so
      intense that they can impede oviposition.

PMID- 15455049
TI  - Triacylglycerol-rich lipophorins are found in the dipteran infraorder
      Culicomorpha, not just in mosquitoes.
AB  - Lipophorin is the major hemolymph protein responsible for lipid transport between
      tissues of insects. Lipophorins from several insect species in order Diptera (the
      fruit fly Drosophila melanogaster from the suborder Brachycera, the mosquito
      Aedes aegypti; the phantom midges Chaoborus maximus and minimus; the black fly
      Simulium vittatum; the crane fly Nephrotoma abbreviata, all from the suborder
      Nematocera) were isolated and characterized. All lipophorins consisted of two
      protein subunits of approximately 240 and 75 kDa each. The density of each
      lipophorin was in the high-density lipoprotein range (1.112 to 1.128 g/ml). The
      predominant neutral lipid carried by lipophorin from insects belonging to the
      infraorder Culicomorpha was triacylglycerol. Lipophorin from the crane fly
      Nephrotoma abbreviata, which belongs to the infraorder Tipulomorpha, carried
      approximately equivalent amounts of diacylglycerol and triacylglycerol.
      Lipophorin from D. melanogaster was found to carry diacylglycerol as the
      predominant neutral lipid.

PMID- 15455050
TI  - Abstracts of the XV International Ecdysone Workshop. June 30- July 6, 2002.
      Kolymbari Crete, Greece.

PMID- 15455051
TI  - Abstracts of the Fourth International Symposium on Molecular Insect Science. May
      28-June 2, 2002. Tucson, Arizona, USA.

PMID- 15455052
TI  - A quantification of predation rates, indirect positive effects on plants, and
      foraging variation of the giant tropical ant, Paraponera clavata.
AB  - While a clear consensus is emerging that predators can play a major role in
      shaping terrestrial communities, basic natural history observations and simple
      quantifications of predation rates in complex terrestrial systems are lacking.
      The potential indirect effect of a large predatory ant, Paraponera clavata
      Fabricius (Formicidae: Ponerinae), on herbivores was determined on rainforest
      trees at La Selva Biological Station in Costa Rica and Barro Colorado Island in
      Panama. Prey and other food brought back to nests by 75 colonies of P. clavata
      were quantified, taking into account temporal, seasonal, and microhabitat
      variation for both foraging activity and composition of foraging booty. The
      dispersion and density of ant colonies and combined density with the mean amounts
      of prey retrieval were used to calculate rates of predation per hectare in the
      two forests. In addition, herbivory was measured on trees containing P. clavata
      and on trees where the ants were not foraging. Colonies at La Selva brought back
      significantly more nectar plus prey than those at Barro Colorado Island, but
      foraging patterns were similar in the two forests. At both forests, the ants were
      more active at night, and there was no significant seasonal or colonial variation
      in consumption of nectar, composition of foraging booty, and overall activity of
      the colonies. At La Selva, trees containing P. clavata colonies had the same
      levels of folivory as nearest neighbor trees without P. clavata but had
      significantly lower folivory than randomly selected trees. Predation by this ant
      was high in both forests, despite its omnivorous diet. This insect predator is
      part of potentially important top-down controls in these wet and moist forests.

PMID- 15455053
TI  - Stabilization of cucurbitacin E-glycoside, a feeding stimulant for diabroticite
      beetles, extracted from bitter Hawkesbury watermelon.
AB  - Cucurbitacins are feeding stimulants for diabroticite beetles, including corn
      rootworms and cucumber beetles, which can be added to a bait containing an
      insecticide thereby reducing the levels of other insecticide treatments needed to
      control these pests. One of them, cucurbitacin E-glycoside, is water soluble and
      easily processed from mutant bitter Hawkesbury watermelons (BHW) that express
      elevated levels of cucurbitacin. Storage of BHW extract at room temperature
      resulted in a 92% reduction of cucurbitacin E-glycoside over two months, while
      refrigeration or freezing resulted in a 60% loss of the active ingredient during
      this time. The loss of the active ingredient was correlated with an increase in
      BHW extract pH from 5 to greater than 9. The increase in pH of the BHW extracts
      at room temperature appeared to be due to the growth of certain bacteria,
      especially Bacillusspp. In refrigerated extracts, the pH remained relatively
      constant, and bacterial growth was dominated by bacteria such as Lactobacilli. An
      alternative to refrigeration is concentration of BHW extract. One means of
      concentration is spray drying, but the high sugar content of the BHW extract
      (20mg/ml glucose, 40mg/ml fructose) makes this technique impractical.
      Fermentation of the BHW extract by the yeast, Saccharomyces boulardii, eliminated
      the sugars and did not raise the pH nor alter the cucurbitacin E-glycoside
      content of the extract. Elimination of the sugars by fermentation produced an
      extract that could be successfully spray dried. BHW extract fermented by S.
      boulardii produced a higher level of feeding stimulation for spotted cucumber
      beetles in laboratory choice tests. When applied to cucumbers, there was no
      difference in control of spotted and striped cucumber beetles between baits of
      fresh or fermented juices combined with the same insecticide.

PMID- 15455054
TI  - Ecdysteroids, juvenile hormone and vitellogenesis in the cockroach Leucophaea
      maderae.
AB  - Topical application of 400 micro g of the juvenile hormone analog, methoprene, to
      females of the penultimate instar of Leucophaea maderae failed to induce
      vitellogenin synthesis. However, last instar females showed an increasing
      response level in making vitellogenin as they aged during the first half of the
      instar. In the second half of the last instar the response to methoprene declined
      to nearly zero when the prothoracic glands have become highly active. Then, a few
      days before the metamorphic molt the responsiveness reached maximal levels, i.e.,
      comparable to adult females. These data suggest that the fat body develops
      competency to produce vitellogenin during the last nymphal instar, but increasing
      titers of ecdysone then interfere with the action of methoprene and consequently
      production of vitellogenin is curtailed. When prothoracic glands from the second
      half of the last instar were implanted into adult females, the normal activation
      of the corpora allata, or their accelerated activation induced by mating, did not
      occur. Likewise, an activation of the corpora allata due to the severance of the
      NCCI was not observed when prothoracic glands had been implanted prior to such
      operations. Thus, ecdysone released by the prothoracic glands appeared to
      directly inhibit the isolated corpora allata in vivo i.e. without the mediation
      by the brain. Methoprene applied to allatectomized adult females induced
      vitellogenin synthesis in a dose dependent manner. This induction was, however,
      quantitatively reduced by implanted active prothoracic glands, particularly when
      low doses of methoprene had been applied. Methoprene higher than 5 micro g
      overcame the inhibitory potency of the implanted prothoracic glands. The effect
      of the prothoracic glands, i.e. ecdysone, appears to signal an interference with
      the action of methoprene at the target tissues, the fat body. The exposure of the
      fat body to a given juvenile hormone/ecdysone ratio dictates the apparent
      effectiveness of ecdysone. The precise mode of the interaction of juvenile
      hormone and ecdysone on the adult fat body is not known. These data show that
      ecdysone inhibits vitellogenesis by two independent mechanisms: 1) inhibition of
      the corpora allata resulting in the inhibition of juvenile hormone production and
      2) inhibition of vitellogenin synthesis by the fat body. Both of these mechanisms
      appear to be operative in immature and mature animals. However, the action of
      ecdysones on the fat body is only seen after it had acquired competency to make
      vitellogenin during the last nymphal instar.

PMID- 15455055
TI  - Decreased survival of mosquito cells after stable transfection with a Drosophila
      ecdysteroid response element: possible involvement of a 40 kDa DNA binding
      protein.
AB  - Homologous transfection systems provide a useful tool for characterizing
      promoters and other regulatory elements from cloned genes. We have used cultured
      Aedes albopictus C7-10 mosquito cells to evaluate expression of 20
      hydroxyecdysone-inducible genes. Although this cell line has previously been
      shown to synthesize components of the ecdysteroid receptor and ecdysone-inducible
      proteins, the well-characterized ecdysteroid response element (EcRE) from the
      Drosophilahsp27 promoter failed to confer a substantial 20-hydroxyecdysone
      mediated induction in transfected mosquito cells. Recovery of stably transformed
      clones was also reduced in a DNA dependent manner when the EcREs were in the
      sense orientation, relative to control plasmids lacking the EcREs or containing
      an antisense construct. Finally, when tandem EcREs were placed within the hsp70
      promoter, CAT activity was detected only after prolonged enzyme incubation,
      suggesting that the DNA interfered with cellular metabolism. In these constructs,
      we noted that the promoter DNA contained several potential binding sites for the
      activator protein-1 (AP-1) transcription factor, one of which lay between the
      tandem EcREs. On southwestern blots, a 40 kDa nuclear protein from C7-10 cells
      bound to DNA containing AP-1 sites. A DNA affinity column was used to partially
      purify the 40 kDa protein, and western analysis showed that the mosquito protein
      cross-reacted with a heterologous antibody to JUN. Likewise, mRNA from C7-10
      cells cross-hybridized with the jun cDNA from Drosophila. These results suggest
      that like estrogen, 20-hydroxyecdysone interfaces with AP-1 as a co-activator
      protein that modulates the overall hormone response.

PMID- 15455056
TI  - Extended parental care in communal social groups.
AB  - Recent developments in social insect research have challenged the need for close
      kinship as a prerequisite for the evolution of stable group living. In a model
      communal bee species, Lasioglossum (Chilalictus) hemichalceum, previous allozyme
      work indicated that groups of cooperating adult females are not relatives. Yet at
      any given time, not all group members perform the risky task of foraging. We
      previously hypothesized that tolerance for non-foragers was a component of
      extended parental care, previously known only for kin based social systems. DNA
      microsatellites were used to study colony genetic structure in order to test this
      hypothesis. Microsatellite polymorphism was substantial (He = 0.775). Overall
      intracolony relatedness, mainly of immatures, was low but significant in nine,
      late season nests (r = 0.136 +/- 0.023), indicating that broods contain five to
      six unrelated sib ships. Detailed analyses of kinship between pairs of
      individuals revealed that most pairs were unrelated and most related pairs were
      siblings. Mothers are absent for 89-91% of the developing immature females, and
      97% of developing males. Alternatively, 46% of adult females had neither sibs nor
      offspring in their nests. These findings indicate that the extended parental care
      model applies broadly to both kin based and nonkin based social systems in the
      Hymenoptera.

PMID- 15455057
TI  - Discontinuous gas exchange in a tracheate arthropod, the pseudoscorpion Garypus
      californicus: occurrence, characteristics and temperature dependence.
AB  - The discontinuous gas exchange cycle of the pseudoscorpion Garypus californicus,
      mean mass 5.9 mg, is rudimentary and is characterized by bursts of CO(2) at
      frequencies ranging from 3.6 mHz at 15 degrees C to 13.3 mHz at 35 degrees C. The
      mean volume of CO(2) emitted per burst is 3.6 micro l g(-1) at 25 degrees C,
      about a tenth of the amount emitted by tracheate arthropods with a well developed
      discontinuous gas exchange cycle. Interburst CO(2) emission is high and increases
      with temperature, reaching near 45% of total CO(2) production rate at 35 degrees
      C. No fluttering spiracle phase is evident. The metabolic rate of G. californicus
      at 25 degrees C (8.4 micro W) is typical of other arthropods. We infer from the
      high rate of interburst CO(2) emission in G. californicus that trans-spiracular
      O(2) partial pressure gradients are small and that spiracular conductance is
      correspondingly high, which may lead to high rates of respiratory water loss
      relative to arthropods with more stringent spiracular control and higher CO(2)
      buffering capacity. The typical moist, hypogeal environments and small body sizes
      of pseudoscorpions correlate well with their respiratory physiology.

PMID- 15455058
TI  - Karyotype, C- and G-band patterns and DNA content of Callimenus (=Bradyporus)
      macrogaster macrogaster.
AB  - Chromosomes and detailed karyotype information (the number, shape, relative
      length, arm ratio, centromeric index) of Callimenus (=Bradyporus) macrogaster
      macrogaster Lef. (Orthoptera: Tettigonioidea, Bradyporini) of Turkey belonging to
      the subfamily Bradyporinae are described. The diploid number of chromosomes was
      found to be 2n male symbol = 23, with 2 metacentric pairs, 2 submetacentric
      pairs, 6 acrocentric pairs. The X chromosome is metacentric. This species has a
      XX female symbol / X0 male symbol sex determining mechanism. The basic karyotype
      is complemented by a description of C- and G-banding patterns. The C-banding
      pattern in spermatogonial metaphase was characterized by the presence of
      paracentromeric C-bands in all chromosomes, and a distal C-band in chromosome 5.
      The G-banding pattern was complex. The 2C nuclear DNA content was found to be
      10.26 +/- 0.16 picograms by microspectrophotometry.

PMID- 15455059
TI  - Structure-based analysis of the ultraspiracle protein and docking studies of
      putative ligands.
AB  - The ultraspiracle protein (USP) is the insect ortholog of the mammalian retinoid
      X receptor (RXR). Fundamental questions concern the functional role of USP as the
      heterodimerization partner of insect nuclear receptors such as the ecdysone
      receptor. The crystallographic structures of the ligand binding domain of USPs of
      Heliothis virescens and Drosophila melanogaster solved recently show that helix
      12 is locked in an antagonist conformation raising the question whether USPs
      could adopt an agonist conformation as observed in RXRalpha. In order to
      investigate this hypothesis, a homology model for USP is proposed that allows a
      structural analysis of the agonist conformation of helix 12 based on the sequence
      comparison with RXR. For USP, one of the main issues concerns its function and in
      particular whether its activity is ligand independent or not. The x-ray
      structures strongly suggest that USP can bind ligands. Putative ligands have
      therefore been docked in the USP homology model. Juvenile hormones and juvenile
      hormone analogs were chosen as target ligands for the docking study. The
      interaction between the ligand and the receptor are examined in terms of the
      pocket shape as well as in terms of the chemical nature of the residues lining
      the ligand binding cavity.

PMID- 15455060
TI  - Characterization of Z/E11- and Z9-desaturases from the obliquebanded leafroller
      moth, Choristoneura rosaceana.
AB  - A (triangle up) 11-desaturase gene was cloned from the sex pheromone gland of the
      obliquebanded leafroller moth, Choristoneura rosaceana. The desaturase cDNA
      sequence spans 1300 nucleotides with an open reading frame encoding a 335 amino
      acid protein, which has 81% identity to a Z/E11-desaturase of the redbanded
      leafroller moth, Argyrotaenia velutinana. A functional assay with a pYES2 yeast
      expression system demonstrated that the (triangle up) 11-desaturase exhibits
      unusual substrate and stereospecificities in producing a Z/E11 mixture (7:1) of
      only C14 acids. A metabolic Z9-desaturase also was cloned from fat body of this
      species, and proved to be in the class that produces more Z9-16:Acid than Z9
      18:Acid.

PMID- 15455061
TI  - A single gene (yes) controls pigmentation of eyes and scales in Heliothis
      virescens.
AB  - A yellow-eyed mutant was discovered in a strain of Heliothis virescens, the
      tobacco budworm, that already exhibited a mutation for yellow scale, y. We
      investigated the inheritance of these visible mutations as candidate markers for
      transgenesis. Yellow eye was controlled by a single, recessive, autosomal factor,
      the same type of inheritance previously known for y. Presence of the recombinant
      mutants with yellow scales and wild type eyes in test crosses indicated
      independent segregation of genes for these traits. The recombinant class with
      wild type scales and yellow eyes was completely absent and there was a
      corresponding increase of the double mutant parental class having yellow scales
      and yellow eyes. These results indicated that a single factor for yellow eye also
      controlled yellow scales independently of y. This gene was named yes, for yellow
      eye and scale. We hypothesize that yes controls both eye and scale color through
      a deficiency in transport of pigment precursors in both the ommochrome and
      melanin pathways. The unlinked gene y likely controls an enzyme affecting the
      melanin pathway only. Both y and yes segregated independently of AceIn,
      acetylcholinesterase insensitivity, and sodium channel hscp, which are genes
      related to insecticide resistance.

PMID- 15455062
TI  - Storage hexamer utilization in two lepidopterans: differences correlated with the
      timing of egg formation.
AB  - Most insects produce two or more storage hexamers whose constituents and
      developmental profiles are sufficiently different to suggest specialization in
      the ways that they support metamorphosis and reproduction. Hexamerin
      specializations are compared here in the Cecropia moth (Hyalophora cecropia),
      which produces eggs during the pupal-adult molt, and the Monarch butterfly
      (Danaus plexippus), which produces eggs under long-day conditions after adult
      eclosion. In both sexes of both species, reserves of arylphorin (ArH) were
      exhausted by the end of metamorphosis. In Cecropia, the same was true for the
      high-methionine hexamerins, V-MtH and M-MtH. But in short day Monarch females 20
      30% of the pupal reserves of V-MtH and M-MtH survived metamorphosis, persisting
      until long-day conditions were imposed to stimulate egg formation. Differences in
      storage sites have been documented in other lepidopterans, with MtH reserves
      being found primarily in fat body protein granules and the ArH reserve being
      found primarily in the hemolymph. Similar differences could explain how a
      fraction of the MtH's, but not of ArH, escapes utilization during metamorphosis
      in a species with post-eclosion egg formation. No differences in utilization
      schedules were detected between V- and M-MtH, despite divergent compositions and
      antigenic reactivity.

PMID- 15455063
TI  - Distribution of ovary ecdysteroidogenic hormone I in the nervous system and gut
      of mosquitoes.
AB  - Ovary ecdysteroidogenic hormone I (OEH I) is a gonadotropin in the female
      mosquito, Aedes aegypti. Whole-mount immunocytochemistry using OEH I antisera
      revealed an extensive distribution of immunostained cells in larvae and adults of
      this mosquito comparable to that observed in the African malaria mosquito,
      Anopheles gambiae. Medial neurosecretory cells were stained in brains of larvae
      and adult Ae. aegypti. In An gambiae the lateral neurosecretory cells were
      stained more often. In both species, immunostained axons from these cells
      extended out of the brain through the neurohemal organ associated with the aorta
      and branched extensively along the midgut. Immunostained endocrine cells were
      observed in larval and adult midguts of both species. In adults, abdominal
      metameric perivisceral organs were stained. Stained axons interconnected the
      perivisceral organs and neurosecretory cells in the abdominal ganglia. Episodic
      release of OEH I from these organs was evident in female Ae. aegypti, when
      staining disappeared at 12 hours after a blood meal and returned by 48 hours to
      levels observed before and up to 2 hours after the blood meal. Two sites were
      specifically stained only in An. gambiae: an axon net around the pyloric valve in
      the hindgut of larvae and adults and a ring of endocrine cells in the cardiac
      valve in the larval midgut. The markedly similar localizations of immunostained
      cells in larvae and adults of two distantly related species indicate that OEH I,
      or a homolog, is conserved within this group of Diptera and likely has stage- and
      sex-specific functions.

PMID- 15455064
TI  - Chemical and physical analyses of wax ester properties.
AB  - Wax esters are major constituents of the surface lipids in many terrestrial
      arthropods, but their study is complicated by their diversity. We developed a
      procedure for quantifying isomers in mixtures of straight-chain saturated and
      unsaturated wax esters having the same molecular weights, using single-ion
      monitoring of the total ion current data from gas chromatography-mass
      spectrometry. We examined the biological consequences of structural differences
      by measuring the melting temperatures, T(m), of >60 synthetic wax esters,
      containing 26-48 carbon atoms. Compounds containing saturated alcohol and acid
      moieties melted at 38-73 degrees C. The main factor affecting T(m) was the total
      chain length of the wax ester, but the placement of the ester bond also affected
      T(m). Insertion of a double bond into either the alcohol or acid moiety decreased
      T(m) by approximately 30 degrees C. Simple mixtures of wax esters with n-alkanes
      melted several degrees C lower than predicted from the melting points of the
      component lipids. Our results indicate that the wax esters of primary alcohols
      that are most typically found on the cuticle of terrestrial arthropods occur in a
      solid state under physiological conditions, thereby conferring greater
      waterproofing. Wax esters of secondary alcohols, which occur on melanopline
      grasshoppers, melted >60 degrees C below primary esters of the same molecular
      weight and reduced T(m) of the total surface lipids to environmental values.

PMID- 15455065
TI  - Cross-resistance and resistance longevity as induced by bean leaf beetle,
      Cerotoma trifurcata and soybean looper, Pseudoplusia includens herbivory on
      soybean.
AB  - Cross-resistance, and longevity of resistance, induced by the bean leaf beetle,
      Cerotoma trifurcata, was studied IN the soybean PI 227687 that exhibited induced
      response in earlier studies. Bean leaf beetle adults and soybean looper,
      Pseudoplusia includens, larvae were used to induce resistance and to determine
      beetle feeding preference. Beetles were collected from soybean fields 2 to 5 days
      prior to the feeding preference test. The level of cross-resistance induced by
      soybean looper herbivory to subsequent bean leaf beetle feeding was higher when
      compared to cross-resistance induced by bean leaf beetle herbivory against
      subsequent feeding by soybean looper. Further, herbivory by the bean leaf beetle
      also induced resistance against soybean looper feeding. In the longevity study,
      leaflets from treated plants were collected 5, 10, 12, 14, 16, 20 and 25 days
      after initiation of feeding. Pairwise comparisons of leaflets from plants treated
      by bean leaf beetle herbivory with untreated plants revealed that induced
      responses were highest 14 and lowest 25 days after initiation of feeding. On
      other sampling days, levels of induced response varied with the sampling day.

PMID- 15455066
TI  - Responses of two ladybeetles to eight fungicides used in Florida citrus:
      implications for biological control.
AB  - Two ladybeetles, Cycloneda sanguinea and Harmonia axyridis, were exposed in the
      laboratory to eight fungicide formulations commonly used in citrus production in
      Florida. Both benomyl and the combination of copper and petroleum oil proved
      toxic to larvae of C. sanguinea that were exposed to concentrations corresponding
      to recommended field rates, either as leaf residues or in topical spray
      applications. Larvae of C. sanguinea also suffered significant mortality when
      exposed to neem oil as a leaf residue, but not after topical application. Larvae
      of H. axyridis exposed to these compounds completed development with the same
      success as control larvae in all trials. However, H. axyridis larvae exhibited
      slower development following exposure to leaf residues of ferbam applied at twice
      the recommended rate. Exposure to azoxystrobin as a leaf residue at twice the
      recommended concentration resulted in accelerated larval development in both
      species. No compounds appeared repellent to adult beetles of either species.
      Adult beetles of both species were observed resting on portions of filter paper
      treated with fosetyl-Al more often than on untreated, control portions.
      Azoxystrobin, ferbam and mefenoxam similarly arrested the movement of adult C.
      sanguinea, whereas benomyl and the copper and petroleum oil combination arrested
      the movement of adult H. axyridis. The differential sensitivity of the two
      coccinellid species is discussed in the context of the potential displacement of
      the indigenous C. sanguinea by the invasive H. axyridis.

PMID- 15455067
TI  - Artificial diets for rearing the Colorado potato beetle, Leptinotarsa
      decemlineata.
AB  - Colorado potato beetles have been reared successfully through 12 generations on
      artificial diets containing either 2.5% potato leaf powder or 2.5% lettuce leaf
      powder/0.75% potato leaf powder. For all but one of the treatment groups, the
      mean duration of each of the four larval stages was between 0.8 and 1.5 days
      longer than the durations exhibited by control beetles that had been fed on
      potato leaves. Maximum weights of prepupae, newly emerged adults and day 5-9
      adults were approximately 78, 80 and 82%, respectively, of the weights for
      comparable stages of control beetles. Mean percent mortality for 1(st) instars
      was two to six times higher for artificial diet-fed CPBs than for leaf-fed
      beetles. However, since pupal mortality was four times higher for control beetles
      than for beetles reared on artificial diet, mean percent total mortality (newly
      hatched through the 9 day old adult) was equivalent for leaf-fed beetles and for
      later generations of potato and Lettuce+Potato diet-fed CPBs. Hemolymph
      ecdysteroid levels and fluctuations in mature 4th instar larvae and prepupae were
      similar in controls and experimental groups. Number of hatchlings produced per
      adult pair per day (fertility) was approximately eight times greater in control
      beetles than in later generations of artificial diet-fed beetles, primarily
      because fewer egg masses were laid per day, percent hatch was lower and
      cannibalism of eggs was higher in these latter groups. Interestingly, the mean
      percent hatch, although only 68% of the control value, was 1.5 times greater for
      beetles reared on diet containing lettuce-leaf powder, and a small percentage of
      potato leaf powder, than on diet containing only potato leaf powder. Percent
      hatch was equal for beetles fed on diet containing only lettuce-leaf powder and
      those fed on potato leaves. Finally, it is noteworthy that the quality of eggs,
      as judged by the ability of the wasp parasitoid, Edovum puttleri, to parasitize
      and develop in the eggs, was similar for eggs produced by control beetles and for
      those produced by beetles fed on potato and Lettuce+Potato diets. The diets and
      rearing system described here will be useful for providing beetles on a year
      round basis for experiments designed to evaluate the effects of potential insect
      control agents, to investigate the mechanism(s) by which insects become resistant
      to control agents and for other applied and fundamental studies related to the
      control of this serious pest. The use of lettuce leaf powder in place of most of
      the potato leaf powder is especially advantageous because of the much reduced
      cost and greater availability of lettuce as compared to potato leaves.

PMID- 15455068
TI  - Individual and population variation in invertebrates revealed by Inter-simple
      Sequence Repeats (ISSRs).
AB  - PCR-based molecular markers are well suited for questions requiring large scale
      surveys of plant and animal populations. Inter-simple Sequence Repeats or ISSRs
      are analyzed by a recently developed technique based on the amplification of the
      regions between inverse-oriented microsatellite loci with oligonucleotides
      anchored in microsatellites themselves. ISSRs have shown much promise for the
      study of the population biology of plants, but have not yet been explored for
      similar studies of animals. The value of ISSRs is demonstrated for the study of
      animal species with low levels of within-population variation. Sets of primers
      are identified which reveal variation in two aphid species, Acyrthosiphon pisum
      and Pemphigus obesinymphae, in the yellow fever mosquito Aedes aegypti, and in a
      rotifer in the genus Philodina.

PMID- 15455069
TI  - A helium burst biolistic device adapted to penetrate fragile insect tissues.
AB  - To compensate for the extremely low penetration efficiency of the original
      PDS/1000-He Bio Rad biolistic device and the deleterious blast effect, design
      modifications have been made to the launching module. These modifications were
      evaluated on Bombyx mori embryos and fragile tissues, such as oocytes and
      imaginal wing disks. The original floppy macrocarrier was replaced by a rigid
      macrocarrier to avoid the effects of the helium blast. The efficiency of the gene
      gun bombardment was reinforced by the addition of a focusing nozzle. The reduced
      blast effect allowed us to carry out high-pressure shootings to small organs with
      improved penetration. This system allowed potentially all the internal embryonic
      tissues to be transfected with optimal survival rates. The new module was
      effective on tissues that are difficult to transfect, such as the epithelial wing
      disk that is covered by a peripodial membrane, and the ovarian follicle cells
      that lie under the ovariole cell membrane. The new macrocarrier allowed both an
      aqueous delivery of particles and an ethanolic dry delivery. No significant
      differences were noted between these two modes of delivery. The major improvement
      is the possibility of high pressure shooting correlated with appreciable
      penetration and a weak blast effect.

PMID- 15455070
TI  - Characterization of an endogenous gene expressed in Aedes aegypti using an orally
      infectious recombinant Sindbis virus.
AB  - Sindbis virus expression vectors have been used successfully to express and
      silence genes of interest in vivo in several mosquito species, including Aedes
      aegypti, Ae. albopictus, Ae. triseriatus,Culex pipiens, Armigeres subalbatus and
      Anopheles gambiae. Here we describe the expression of an endogenous gene,
      defensin, in Ae. aegypti using the orally infectious Sindbis virus, MRE/3'2J
      expression vector. We optimized conditions to infect mosquito larvae per os using
      C6/36Ae. albopictus cells infected with the recombinant virus to maximize virus
      infection and expression of defensin. Infection with the parental Sindbis virus
      (MRE/3'2J) did not induce defensin expression. Mosquito larvae infected by
      ingestion of recombinant Sindbis virus-infected C6/36 cells expressed defensin
      when they emerged as adults. Defensin expression was observed by western analysis
      or indirect fluorescent assay in all developmental stages of mosquitoes infected
      with MRE/3'2J virus that contained the defensin insert. The multiplicity of
      infection of C6/36 cells and the quantity of infected cells consumed by larvae
      played an important role in defensin expression. Parental viruses, missing the
      defensin insert, and/or other defective interfering virus may have contributed to
      these observations.

PMID- 15455071
TI  - The role of low levels of juvenile hormone esterase in the metamorphosis of
      Manduca sexta.
AB  - The activity of juvenile hormone esterase (JHE) in feeding fifth instar larvae of
      Manduca sexta increases gradually with larval weight and rises to a peak after
      larvae pass the critical weight when juvenile hormone secretion ceases.
      Starvation of larvae of Manduca sexta (L.) that had exceeded the critical weight
      inhibited peak levels of JHE, but did not delay entry into the wandering stage
      when larvae leave the plant in search of a pupation site. This suggests that peak
      levels of JHE may not be essential for the normal timing of metamorphosis.
      Starved larvae pupated normally, indicating the peak of JHE was not necessary for
      a morphologically normal pupation. Treatments of larvae with the selective JHE
      inhibitor O-ethyl-S-phenyl phosphoramidothiolate (EPPAT) that began immediately
      after larvae achieved the critical weight (6.0 to 6.5 grams for our strain of
      Manduca) delayed entry into the wandering stage. By contrast, EPPAT treatment of
      larvae at weights above 8.0 g had no effect on the subsequent timing of the onset
      of wandering. Therefore, although the normal timing of the onset of wandering
      does not require peak levels of JHE, it requires low to moderate levels of JHE to
      be present until larvae reach a weight of about 8.0 g.

PMID- 15455072
TI  - Tissue distribution and lipophorin transport of hydrocarbons and sex pheromones
      in the house fly, Musca domestica.
AB  - We investigated the relationship between epicuticular and internal hydrocarbons
      in the adult house fly, Musca domestica and the distribution of hydrocarbons,
      including the female sex pheromone component, (Z)-9-tricosene, in tissues.
      Internal hydrocarbons increased dramatically in relation to sexual maturation and
      were found in the hemolymph, ovaries, digestive tract, and fat body. (Z)-9
      Tricosene comprised a relatively large fraction of the hydrocarbons in the female
      carcass and hemolymph, and less so in other tissues, while other hydrocarbons
      were represented in greater amounts in the ovaries than in other tissues. It
      therefore appears that certain hydrocarbons were selectively provisioned to
      certain tissues such as the ovaries, from which pheromone was relatively
      excluded. Both KBr gradient ultracentrifugation and specific immunoprecipitation
      indicated that > 90% of hemolymph hydrocarbons were associated with a high
      density lipophorin (density = 1.09 g ml(-1)), composed of two apoproteins under
      denaturing conditions, apolipophorin I (approximately 240 kD) and apolipophorin
      II (approximately 85 kD). Our results support a predicted model (Chino, 1985)
      that lipophorin is involved in the transport of sex pheromone in M. domestica. In
      addition to delivering hydrocarbons and sex pheromones to the cuticular surface,
      we suggest that lipophorin may play an important role in an active mechanism that
      selectively deposits certain subsets of hydrocarbons at specific tissues.

PMID- 15455073
TI  - Potential factors impacting season-long expression of Cry1Ac in 13 commercial
      varieties of Bollgard cotton.
AB  - Thirteen commercial varieties of transgenic Cry1Ac Bacillus thuringiensis
      Berliner (Bt) cotton were examined across two sites in 2000 for potential factors
      that impact endotoxin expression. In all cases, two varieties (NuCOTN 33B and DP
      458B/RR, Delta & Pineland Co., Scott, MS) expressed more Cry1Ac than the other 11
      varieties in various plant structures. These two varieties share the same
      parental background (DP 5415). Furthermore, when the next generation of plants
      were tested in the greenhouse, the same varietal patterns were exhibited. These
      data strongly suggest that factors such as parental background had a stronger
      impact on the expression of Cry1Ac than the environment.

PMID- 15455074
TI  - Gene recruitment of the activated INO1 locus to the nuclear membrane.
AB  - The spatial arrangement of chromatin within the nucleus can affect reactions that
      occur on the DNA and is likely to be regulated. Here we show that activation of
      INO1 occurs at the nuclear membrane and requires the integral membrane protein
      Scs2. Scs2 antagonizes the action of the transcriptional repressor Opi1 under
      conditions that induce the unfolded protein response (UPR) and, in turn, activate
      INO1. Whereas repressed INO1 localizes throughout the nucleoplasm, the gene is
      recruited to the nuclear periphery upon transcriptional activation. Recruitment
      requires the transcriptional activator Hac1, which is produced upon induction of
      the UPR, and is constitutive in a strain lacking Opi1. Artificial recruitment of
      INO1 to the nuclear membrane permits activation in the absence of Scs2,
      indicating that the intranuclear localization of a gene can profoundly influence
      its mechanism of activation. Gene recruitment to the nuclear periphery,
      therefore, is a dynamic process and appears to play an important regulatory role.

PMID- 15455076
TI  - Genotype-dependent changes in pain thresholds in adult mice after neonatal
      treatment.
AB  - We studied the effect of neonatal treatment with pharmacological preparations
      (Semax and buspiron) and solvents (distilled water and physiological saline) on
      the pain threshold in 3-4-month-old mice of 6 genotypes. Neonatal administration
      of the solvent (nociceptive stimulation) decreased pain thresholds in DBA/2,
      101/HY, and RSB males, but not in female mice and animals of other strains.
      Neonatal administration of Semax significantly increased pain thresholds in adult
      DBA/2 and 101/HY males compared to those in animals neonatally treated with the
      solvent. Injection of buspiron in the neonatal period decreased pain thresholds
      in RLB males.

PMID- 15455077
TI  - Immunotropic effects of active immunization with serotonin-protein conjugate in
      C57BL/6 mice exposed to immobilization stress.
AB  - Immobilization stress for 14 h induced lymphopenia, hypoplasia of the thymus and
      spleen, and decrease in functional activity of T lymphocytes and macrophages in
      C57Bl/6 mice. Active induction of antibodies against serotonin during stress
      decreased functional activity of T lymphocytes and partially recovered phagocytic
      activity of peritoneal macrophages.

PMID- 15455078
TI  - Effect of lupus anticoagulant on the interaction of prothrombin with platelets.
AB  - We studied binding of (125)I-labeled prothrombin to platelets in the presence of
      circulating endogenous lupus anticoagulant. Lupus anticoagulant modulated the
      interaction and increased affinity of prothrombin for calcium-independent binding
      sites on platelets. The number of these sites decreased, while the total number
      of calcium-dependent binding sites increased. Our results indicate that lupus
      anticoagulant plays a role in the binding of prothrombin to nonactivated
      platelets.

PMID- 15455079
TI  - Amylolytic activity of small intestinal brush-border membrane in the late
      postresuscitation period.
AB  - Functional changes in the small intestinal brush-border membrane were studied in
      the late recovery period after acute fatal blood loss. Delayed recovery of enzyme
      activity in the small intestinal brush-border membrane was due to impaired
      functional topography of the digestive transport system. It was manifested in a
      shift of the proximodistal gradient toward reserve zones of the ileum.

PMID- 15455080
TI  - Immunoprotective effects of prolactin during stress-induced immune dysfunction.
AB  - We showed for the first time that prolactin stimulates the synthesis and release
      of immunomodulating cytokines and lymphocyte-activating factors (e.g.,
      interleukin-1) by peritoneal macrophages. Prolactin abolished the stress-induced
      inhibition of proliferation of peripheral blood lymphocytes and increased cell
      sensitivity to regulatory effects of interleukin-1 in the reaction of lymphocyte
      blast transformation. These data illustrate the mechanism of immunoprotective
      activity of prolactin during stress.

PMID- 15455081
TI  - Relationship between high sensitivity of suckling mice to hepatocarcinogenic and
      antiglucocorticoid effects of o-aminoazotoluene and diethylnitrosamine.
AB  - Suckling mice were more sensitive to the hepatocarcinogenic effect of various
      carcinogens compared to adult animals. After treatment with o-aminoazotoluene and
      diethylnitrosamine HNF3-DNA-binding capacity and glucocorticoid-induced liver
      tyrosine aminotransferase activity in suckling mice decreased more significantly
      than in adult animals.

PMID- 15455082
TI  - Blebbing of thymocyte plasma membrane and apoptosis are related to impairment of
      capacitance Ca2+ entry into cells.
AB  - We studied the role of disturbances in cell Ca(2+) homeostasis in plasma membrane
      blebbing and death of thymocytes. Capacitance Ca(2+) channels of the plasma
      membrane and intracellular Ca(2+) stores are involved in the induction and
      progression of changes in the membrane and cytoskeleton and apoptosis induced by
      acrylonitrile.

PMID- 15455083
TI  - Ultrastructural and cytochemical changes in the respiratory compartment of the
      lungs in rats after combined treatment with fine silicon dioxide powder and
      uridine.
AB  - Electron microscopy and cytochemical study of alveolar tissue of rat lungs were
      performed at the early stage after intratracheal treatment with fine silicon
      dioxide powder. The preparation was administered to animals receiving or not
      receiving intravenous injection of uridine. Dust particles permeated the
      cytoplasm, mitochondria, and nuclei of cells in the air-blood barrier of the
      alveoli. Uridine decreased the severity of dust-induced damage to cells and
      increased intracellular glycogen content.

PMID- 15455084
TI  - Wound-healing effect of papaya-based preparation in experimental thermal trauma.
AB  - Treatment with the phytopreparation from papaya accelerated wound healing and
      reduced the severity of local inflammation in rats with burn wounds. The effect
      of this phytopreparation can be related to an increase in the effectiveness of
      intracellular bacterial killing by tissue phagocytes due to the inhibition of
      bacterial catalase. Antioxidant activity of the preparation decreases the risk of
      oxidative damage to tissues.

PMID- 15455085
TI  - Effect of oxytocin on neuronal activity in amygdaloid nuclei in stressed rats.
AB  - The dynamics of impulse activity of amygdaloid neurons in response to intravenous
      injection of oxytocin were examined in acute experiments on random-bred albino
      rats. Oxytocin modified activity of amygdaloid neurons in intact and stressed
      rats. The dose-dependent effects of oxytocin were manifested in changes in the
      latency of neuronal responses and in rearrangement of their spike activity. The
      oxytocin-induced neuronal responses were less pronounced in cells with high
      baseline activity.

PMID- 15455086
TI  - Preclinical study of the effect of cardiotropic agents on isolated heart.
AB  - Direct effects of cardiotropic preparations on the hearts isolated from Wistar
      rats were examined. Deenergization of cardiomyocytes was modeled under conditions
      of hypoxic perfusion. Recovery of cardiac function during reperfusion was
      assessed by changes in the heart rate and contraction amplitude.

PMID- 15455087
TI  - Cytokine production by immunocompetent cells of peritoneal fluid in women with
      external genital endometriosis.
AB  - The content of some cytokines in the peritoneal fluid and the level of their in
      vitro production by peritoneal macrophages and lymphocytes were evaluated in
      women with external endometriosis. The ratio of peritoneal lymphocytes and
      macrophages in the peritoneal fluid was changed in endometriosis because of
      increased percentage of lymphoid cells and decreased content of macrophages, in
      the presence of high absolute counts of both types of cells. The cytokine status
      of women with endometriosis was characterized by higher levels of IL-1beta, TNF
      alpha, and epidermal growth factors both in the peritoneal fluid and supernatants
      of 24-h cultures of peritoneal macrophages; the content of IFN-alpha remained
      unchanged. The concentrations of IFN-gamma in the peritoneal fluid did not change
      in endometriosis, but increased in the supernatants of peritoneal lymphocyte
      cultures.

PMID- 15455088
TI  - Effect of hyperlipoproteinemia on functional activity of peritoneal macrophages
      during tumor growth.
AB  - The role of hypercholesterolemia as a factor modulating functional activity of
      macrophages during the growth of syngeneic transplanted 22a hepatoma in mice was
      studied. Starting from day 21 after inoculation of tumor cells we observed the
      development of hyperlipoproteinemia paralleled by an increase in macrophage
      activity parameters. The total serum cholesterol content and production of
      nitroxide anions by macrophages were in positive correlation on days 14-35 of
      tumor growth. We hypothesized that the development of hypercholesterolemia at the
      late stages of some tumor growth is a factor stimulating production of nitrites
      and 5'-nucleotidase activity.

PMID- 15455089
TI  - Effects of phosphoinositide cycle modifiers on apoptosis of peritoneal
      macrophages.
AB  - Hydrogen peroxide stimulates apoptosis of zymosan-activated rat peritoneal
      macrophages. Phosphoinositide cycle modifiers enhance the proapoptotic effect of
      H(2)O(2) in a concentration of 1 mM and necrosis-stimulating effect of H(2)O(2)
      in a concentration of 10 mM. Disorders in phosphoinositide metabolism and
      impaired reaction of the cell to proinflammatory agents are the cause of
      programmed cell death. Rejection of defective cells can be realized via variation
      of H(2)O(2) concentration.

PMID- 15455090
TI  - Antimetastatic effect of thymus-dependent antigen (sheep erythrocytes) in C57BL/6
      mice with Lewis carcinoma.
AB  - We revealed an antimetastatic effect of thymus-dependent corpuscular antigen
      (sheep erythrocytes) injected intravenously or intraperitoneally in sensitizing
      or high doses alone or in a complex with a course dose of cyclophosphamide to
      C57Bl/6 mice with Lewis carcinoma. Injection of the antigen appreciably reduced
      the number and volume of Lewis carcinoma metastases in the lungs, notably
      increased the therapeutic effect of cyclophosphamide, and restored hemopoiesis,
      particularly, the red blood stem suppressed by the tumor process and cytostatic
      treatment. The growth of primary tumors virtually did not change. High dose of
      sheep erythrocytes was more effective.

PMID- 15455091
TI  - Effect of liver macrophage depression on the development of liver metastases of
      HA-1 tumor in mice.
AB  - Gadolinium chloride (5 mg/kg) administered to mice 24 h before intravenous
      transplantation of HA-1 hepatoma cells decreased the volume density of tumor
      implants in the liver, reduced the intensity of degenerative and necrotic changes
      developing under the effect of growing tumor metastases, and prolonged the life
      span of tumor-bearing mice. Development of metastases was not associated with
      changes in cathepsin B activity in the liver, while activity of cathepsin L
      decreased only during the early period (4 days) after injection of gadolinium
      chloride. Injection of gadolinium chloride led to labilization of liver cell
      lysosomes because of overload with gadolinium chloride particles. The positive
      effect of gadolinium chloride was probably associated with depression of liver
      macrophages at the stage of tumor cell invasion and with subsequent migration of
      monocytes/macrophages preventing the growth of formed metastatic nodes in the
      liver.

PMID- 15455092
TI  - NO-generating compounds modify tumoritoxic effect of doxorubicin.
AB  - The effects of NO-generating compounds on the tumoritoxic effect of doxorubicin
      was evaluated by changes in DNA synthesis and apoptotic death of Ehrlich
      adenocarcinoma cells in vitro. NO donors significantly inhibited the cytotoxic
      effect of doxorubicin, which manifested in activation of DNA synthesis and
      decreased induction of apoptosis. Presumably, NO acts a factor protecting tumor
      cell DNA from the damaging effect of doxorubicin.

PMID- 15455093
TI  - Expression of argyrophilic proteins in the nucleolar organizer regions of human
      thymocytes and thymic epitheliocytes under conditions of coculturing with vilon
      and epithalon peptides.
AB  - Vilon stimulated and Epithalon suppressed the expression of argyrophilic proteins
      in nucleolar organizer regions of thymocytes and epithelial cells, stimulating or
      reducing, respectively, the formation, assembly, and transport of ribosomes into
      the cytoplasm and thus determining the intensity of protein synthesis in these
      cells. A direct mitogenic effect of Vilon was also revealed: this peptide
      promoted thymocyte transformation into proliferating blast cells.

PMID- 15455094
TI  - Electron microscopic characteristics of peripheral blood lymphocytes in children
      with infectious mononucleosis.
AB  - Infectious mononucleosis is associated with pronounced changes in surface
      architectonics of peripheral blood lymphocytes persisting during convalescence
      and remote period after the disease. The degree of these changes depends on the
      disease agent and age-specific characteristics of the body. The most pronounced
      and sustained disorders in the morphostructural organization of lymphocytes are
      caused by Epstein-Barr virus (in comparison with agents of other etiology); these
      disorders are more pronounced in children aged 7-14 years than in those aged 3-6
      years.

PMID- 15455095
TI  - Effects of pineal peptides on circadian dynamics of spermatogonia proliferation
      in albino rats.
AB  - Mitotic index of type B spermatogonia in intact animals is characterized by a
      circadian rhythm. Mitotic index increased and its circadian rhythm disappeared
      after pinealectomy. Treatment with Epithalamin for 14 days restored the circadian
      rhythm. The circadian biorhythm of spermatogonia proliferation suggests the
      presence of circadian rhythm of spermatogenesis in general and its regulation by
      the pineal gland.

PMID- 15455096
TI  - Comparative analysis of effects of various types of double-stranded RNA on
      cultured human laryngeal cancer cells.
AB  - We compared the effects of Na+ and Ca2+ double-stranded RNA on cultured human
      laryngeal cancer cells by cytomorphometry and cytophotometry. Both agents
      inhibited proliferation and other cell functions, but to a different extent: Ca2+
      double-stranded RNA was more active than Na+ double-stranded RNA.

PMID- 15455097
TI  - Effect of endothelin-1 on apoptosis, proliferation, and protein synthesis in
      cardiomyocytes of newborn albino rats.
AB  - Five intraperitoneal injections of endothelin-1 (100 microg/kg) to newborn albino
      rats on days 2-6 of life did not change the number of nuclei expressing PCNA in
      the left-ventricular myocardium. The number of nucleoli, area and perimeter of
      cardiomyocytes (isolated by the method of alkaline dissociation) increased. The
      number of myocyte nuclei in the state of apoptosis (evaluated by the TUNEL
      method) increased significantly. Presumably, partial loss of cardiomyocytes as a
      result of apoptosis activation after treatment with endothelin-1 is compensated
      by increased size and transcription activity of remaining cardiomyocytes.

PMID- 15455098
TI  - Morphofunctional changes in neurons of hippocampal fields and neocortical layers
      in rats treated with Polydan.
AB  - Light microscopy revealed four types of neurons differing by staining intensity
      and size in each of the pyramidal neuron populations in the dorsal hippocampal
      fields and layer V of the neocortical somatosensory area and in granular cells of
      the dentate fascia and stellate cells of layer II of the same cerebrocortical
      area in rats. Treatment with Polydan according to different protocols led to
      redistribution of these types of cells, which attests to stimulation of synthetic
      processes in these brain areas, rather than to similar sequence of the
      involvement of different brain areas in this process. Polydan promoted the
      increase in the mean number of nucleoli in the nuclei of neurons of all types,
      the degree of this increase being different for each type. It seems that
      morphological signs (staining intensity and number and size of nucleoli in the
      nuclei) reflect certain functional states of the neurons in the homogeneous
      populations. Presumably, various factors can stimulate transition of neurons from
      one morphofunctional status into another.

PMID- 15455099
TI  - Pathomorphological variants of midventricular obstruction of interventricular
      septum during hypertrophic cardiomyopathy.
AB  - Postmortem contrast cardiac ventriculography, coronarography, volume-mass and
      planimetric cardiometry, as well as echocardiography and pathomorphological data
      correlation technique were employed for examination of the hearts from patients
      died from hypertrophy cardiomyopathy (n=100). The following variants of
      midventricular hypertrophy of the interventricular septum (midventricular
      obstruction) were established: midleft ventricular, midright ventricular,
      midproximal, midmaximal. Isolated distal apex hypertrophy and apical hypertrophy
      were also documented. These variants and forms of cardiac pathology are
      determined by peculiar changes in geometrical structure of the septum and left
      ventricle. Multiplanar variability and mobility of interventricular septum
      combined with peculiar catenary shape promote specific abnormalities of
      intracardiac hemodynamics determining dissociation between the echocardiographic
      and pathomorphological diagnostic data and underlying the leading elements of
      patho- and thanatogenesis of hypertrophic cardiomyopathy.

PMID- 15455100
TI  - Ultrastructural changes in the cilia of experimental mice.
AB  - Mice lacking dynein arms in the cilia were examined; the strain was obtained by
      inactivation of dynein heavy chain gene in chromosome 7. The cilia of these mice
      were examined by electron microscopy and compared to the cilia of random-bred
      mice. No statistically significant differences or typical disorders in the outer
      or inner dynein arms were detected. The number of inner dynein arms was lower, in
      some cilia secondary changes presenting as swelling of the outer part of the
      ciliary membrane or formation of complex cilia were seen.

PMID- 15455101
TI  - Morphological and functional peculiarities of lymphoid cells in mice of different
      strains.
AB  - We revealed differences in quantitative composition and functional activity of
      lymphoid cells in intact mice of different strains. Cellularity and counts of
      lymphoid elements in hemopoietic and lymphoid organs, proliferative activity of T
      and B lymphocytes, and counts of CD4+ and CD8+ lymphocytes in the spleen were
      minimum in CC57W and Balb/c mice and maximum in CBA/CaLac and DBA/2 mice. The
      highest absolute content of lymphoid elements in the spleen was detected in
      Balb/c mice, while CC57W mice had the highest content of these elements in the
      thymus.

PMID- 15455102
TI  - In vitro formation of mesenchymal bone marrow islets.
AB  - We studied the formation of mesenchymal islets in the culture of bone marrow
      cells in vitro. Islet-like structures detected on day 6 of culturing contained a
      central epithelioid cell (differing from macrophages and fibroblasts) surrounded
      with round mesenchymal cells. The number of mesenchymal islets increased on days
      12-14 of culturing, but decreased to zero by the 24th day. They appeared not only
      as individual structures, but also entered the composition of colonies and formed
      assemblies with surrounding cells of different maturity. Our results show that
      mesenchymal islets serve as structural and functional units of mesenchymopoiesis.

PMID- 15455103
TI  - Effect of testosterone derivatives administered to pregnant rats on the brain of
      their offspring (delayed consequences).
AB  - We examined the offspring of rats receiving sustanon with testosterone
      derivatives on day 19 of pregnancy. At the age of 1 month, these rats differed
      from control animals in the indexes of higher nervous activity. The relative
      weight of the brain increased in 54-day-old rats receiving the hormone. Female
      rats were characterized by increased sudanophilia of the white matter in
      cerebellar hemispheres and high RNA content in layer V neurons of the parietal
      lobe, increased volume of nuclei in hippocampal neurons, weight of the ovaries
      (tendency), size of the largest follicles, and high activity of 3beta-ol-steroid
      dehydrogenase. The weight of the adrenal glands and 3beta-ol-steroid
      dehydrogenase activity in adrenocortical cells of the fascicular zone increased
      in male rats.

PMID- 15455104
TI  - Effect of rotating electromagnetic fields on proteolytic activity of pepsin in
      rats.
AB  - We studied the effect of 37-GHz electromagnetic field on proteolytic activity of
      pepsin in Wistar rats. The plane of polarization of the electromagnetic fields
      rotated in either right-handed or left-handed sense (D- and L-chirality). D
      Polarization stimulated, while L-polarization suppressed pepsin production.

PMID- 15455105
TI  - Spatial characteristics of cisterna magna in rats and novel technique for
      puncture with a stereotactic manipulator.
AB  - The actual size and sites for puncture of the cisterna magna in adult Wistar rats
      were estimated on acrylic models. We proposed a new method for obtaining
      cerebrospinal fluid from narcotized rats. This method consists in controlled
      introduction of a needle into the cisterna magna through the skin and/or dura
      mater above this structure using a stereotactic micromanipulator. Experiments on
      rats with focal and global cerebral ischemia showed that this technique ensures
      single and repeated sampling of at least 50 microl liquor not containing blood
      admixtures.

PMID- 15455106
TI  - Effect of delta-rhythm-modulated extremely high frequency electromagnetic
      radiation on rats.
AB  - Extremely high frequency electromagnetic radiation modulated with a frequency
      equal to cerebral delta-rhythm oscillations induced electrosleep in rats.

PMID- 15455107
TI  - Stimulation of vagus nerve modifies negative chronotropic and hypotensive effects
      of adenosine.
AB  - The effects of electrical stimulation of the vagus nerve on the negative
      chronotropic and hypotensive effects of adenosine were studied on adult rats.
      Intravenous injection of adenosine to control rats significantly reduced the
      heart rate and induced a transient blood pressure drop followed its increase.
      Preliminary electrical stimulation of the right vagus nerve reduced the magnitude
      and duration of adenosine-induced bradycardia and changed the dynamics of
      adenosine-induced arterial pressure perturbations.

PMID- 15455108
TI  - Contractile and electrical functions of rat heart during left ventricular
      hypertrophy.
AB  - Left ventricular hypertrophy of the hearts in Wistar rats caused by renovascular
      hypertension prolongs depolarization of epicardial surface of the ventricles and
      increases the duration of excitation phase in the left ventricular epicardium.
      Sex-related differences in changes of myocardial contractility were revealed
      during hypertrophy of the left ventricle caused by renovascular hypertension.

PMID- 15455109
TI  - Role of methionine in nocturnal melatonin peak in the pineal gland.
AB  - Methionine dose-dependently stimulated O-methylation of hydroxyindoles in the
      pineal gland and contributed to the nocturnal melatonin peak in adult male Wistar
      rats. Methionine is involved in the maintenance of diurnal rhythms by regulating
      biochemical transformations of indoles in pinealocytes. Our findings provide
      theoretical basis for new applications of methionine.

PMID- 15455110
TI  - Oxygen-dependent processes in monocytes and metabolic risk factors for
      atherogenesis.
AB  - Oxygen-dependent processes in peripheral blood monocytes were intensified in
      patients with metabolic cardiovascular syndrome. This was manifested in increased
      production of O(2)(*-) and NO. Among metabolic factors (cholesterol, low-density
      lipoprotein cholesterol, high-density lipoprotein cholesterol, triacylglycerols,
      glucose, etc.), products of glycosylation (fructosamine) and plasma
      triacylglycerols were most potent in modulating generation of O(2)(*-) and NO by
      monocytes.

PMID- 15455111
TI  - Elastic modulus of the thin filament under normal conditions and during heart
      failure.
AB  - We developed an original approach to prepare samples for electron microscopy in
      electric field allowing calculation of the Youngs modulus of the thin filament in
      a direction perpendicular to the axis of the filament (longitudinal to the
      protomer) under normal conditions and during heart failure induced by 10-day
      toxic and allergic myocarditis. Electric field stretches thin filaments in the
      transverse direction and the increase in its diameter linearly depends on the
      applied voltage. The elastic modulus was in inverse proportion to the applied
      voltage. We found that during heart failure thin filament had an extreme
      conformation and to a great extent lost its mobility.

PMID- 15455112
TI  - Age-related changes in cadmium content and oxidative modification of proteins in
      different regions of human spinal cord.
AB  - A direct correlation was found between the content of oxidative protein
      modification products in the cervical enlargement of the spinal cord and age in
      humans. We revealed a considerable increase in Cd(2+) concentrations in elderly
      and old people and an increase in Fe(2+) concentration in old people. In the
      lumbosacral enlargement Cd(2+) concentration was maximum and did not vary with
      age. The content of oxidative protein modification products significantly
      increased in the lumbosacral enlargement in older adults and old people.
      Moreover, old people had high content of Cu(2+) in the lumbosacral enlargement.
      Our findings suggest that accumulation of Cd(2+) play a role in the metabolism of
      Cu(2+) and Fe(2+), which contributes to age-related intensification of oxidative
      protein modification in the spinal cord.

PMID- 15455113
TI  - Metabolic effects of mixture containing branched-chain amino acids and taurine
      during subchronic poisoning with barbiturates.
AB  - We studied the effect of a mixture containing branched-chain amino acids and
      taurine on the pool of free amino acids and their derivatives during chronic
      phenobarbital poisoning. Subchronic barbiturate poisoning produced by daily
      intraperitoneal injection of phenobarbital caused imbalance in the content of
      some amino acids in blood plasma and liver of rats. Treatment with the mixture of
      branched-chain amino acids and taurine normalized the content of amino acids in
      the liver and blood plasma of animals with subchronic phenobarbital poisoning.
      The mixture of branched-chain amino acids and taurine corrects metabolic
      processes and normalized the peripheral pool of amino acids. Our findings extend
      the range for application of amino acids in clinical practice.

PMID- 15455114
TI  - HLDF-6 peptide relieves symptoms of abstinence syndrome during experimental opium
      abuse.
AB  - Experiments were performed on rats with opium abuse induced by chronic
      administration of morphine in increasing doses. We studied the effect of HLDF-6
      peptide on symptoms of naloxone abstinence. Repeated administration of HLDF-6
      peptide in a dose of 0.2 mg/kg 24 and 0.5 h before naloxone relieved the major
      symptoms of the abstinence syndrome. A possible neurochemical mechanism
      underlying the effect of HLDF-6 peptide is inhibition of enkephalinase A in
      structures of the endogenous antinociceptive system.

PMID- 15455115
TI  - Effect of melatonin, ascorbic acid, and succinic acid on the cumulative toxic
      effect of repeated treatment with gammafos (amifostine).
AB  - Daily treatment of outbred albino mice with gammafos in radioprotective doses of
      300 and 500 mg/kg for 4 days produced a cumulative toxic effect. This effect was
      not observed after decreasing the dose of gammafos to 100 mg/kg. Repeated peroral
      administration of melatonin and ascorbic acid in a dose of 200 mg/kg 30 min
      before treatment with gammafos reduced its cumulative toxic effect. Succinic acid
      in a dose of 100 mg/kg was ineffective under these conditions. The cumulative
      death time for 50% animals receiving gammafos alone or in combination with
      melatonin, ascorbic acid, and succinic acid was 3.08, 4.29, 4.06, and 2.97 days,
      respectively.

PMID- 15455116
TI  - Role of thrombin in activation of neurons in rat hippocampus.
AB  - The effect of thrombin, an agonist of proteinase-activated receptor (PAR) family,
      was studied on cultured rat hippocampal neurons. Thrombin in a concentration
      range of 1 pM - 10 nM induced a transitory dose-dependent increase in
      intracellular free calcium concentration. Involvement of PAR1 in neural response
      to thrombin was corroborated in experiments with TFLLRN, a selective synthetic
      peptide agonist of these receptors. In a calcium-free medium and after treatment
      with cyclopiazonic acid (inhibitor of Ca(2+)-ATPase in the endoplasmic reticulum)
      activation of PAR not only mobilized Ca(2+) from intracellular stores, but also
      induced Ca(2+) entry into the cells. Thrombin decreased Ca(2+) signal triggered
      by activation of NMDA-subtype glutamate receptors.

PMID- 15455117
TI  - Total antioxidant capacity of blood plasma from healthy donors receiving vitamin
      and mineral complex.
AB  - The total antioxidant capacity (TEAC assay) of blood plasma from healthy donors
      was studied before and after 2- and 4-week consumption of the vitamin and mineral
      complex containing the major antioxidant vitamins and cofactors of antioxidant
      enzymes. Before the treatment the donors were divided into 2 subgroups with
      initially high and low total antioxidant capacity. After 2-week course of vitamin
      and mineral complex the total antioxidant capacity considerably decreased in
      group 1 donors, but increased in group 2 donors. After 4-week course this index
      increased in donors of both subgroups and slightly surpassed the baseline level
      typical of individuals with high total antioxidant capacity.

PMID- 15455118
TI  - Dose-dependent effects and specificity of action of antibodies to endogenous
      regulators in ultralow doses.
AB  - We studied the effects of antibodies against interferon-gamma, erythropoietin,
      and tumor necrosis factor-alpha in ultralow doses on the production of endogenous
      interferon-gamma. Course peroral treatment with potentiated antibodies to
      interferon-gamma in various dilutions produced similar changes in experimental
      animals. The treatment stimulated spontaneous production of endogenous interferon
      gamma by mouse lymphocytes. It should be emphasized that antibodies to other
      cytokines in ultralow doses did not stimulate interferon-gamma production. These
      data illustrate the specificity of action of antibodies to endogenous regulators
      in ultralow doses.

PMID- 15455119
TI  - Metabolic correction of gas exchange disturbances in rats with barbiturate coma.
AB  - Krebs cycle intermediates normalized gas exchange and decreased the mortality
      rate in rats with barbiturate coma. Treatment with other substrates including
      glucose and products of glycolysis was ineffective. Oxygen inhalation had no
      effect on oxygen consumption and indexes of external respiration. Our results
      suggest that deficiency of endogenous intermediates of the Krebs cycle, but not
      disturbances in oxygen mass transfer, serves as a limiting factor for oxygen
      consumption in rats with barbiturate coma.

PMID- 15455120
TI  - Effect of M2 muscarinic receptor blockade in rats with haloperidol-produced
      catatonic syndrome.
AB  - We studied the functional role of individual subtypes of muscarinic
      cholinoceptors in the pathogenesis of neuroleptic parkinsonism in rats. Blockade
      of M4 receptors prevented the development of extrapyramidal disorders, which was
      abolished by simultaneous blockade of M2 receptors. The data suggest that various
      subtypes of muscarinic receptors are involved in the regulation of dopamine
      concentration.

PMID- 15455121
TI  - Effect of baikal skullcap extract administered alone or in combination with
      cyclophosphamide on natural cytotoxicity system in mice with Lewis lung
      carcinoma.
AB  - Baikal skullcap extract was introduced into cytostatic therapy of mice with Lewis
      lung carcinoma. This extract potentiated the antimetastatic effect of
      cyclophosphamide in mice with grafted tumors. Combined treatment with
      cyclophosphamide and extract of Baikal skullcap modulated cytotoxic activity of
      natural killer cells and peritoneal macrophages during tumor growth.

PMID- 15455122
TI  - Suppression of growth and metastasizing of T-cell lymphoma in mice infected with
      american trypanosomiasis at different stages of experimental infection.
AB  - Antitumor activity of Trypanosoma cruzi CH4 strain isolated in Mexico was
      studied. This parasite is not tumoritropic, but inhibits the growth and
      metastasizing of solid L5178Y-R lymphoma transplanted to Balb/C mice. Conditioned
      medium from cell cultures infected with this strain produced a cytostatic effect.
      Possible mechanisms of this phenomenon are discussed.

PMID- 15455123
TI  - Invasive characteristics of apathogenic Shigella flexneri 5a2c mutant obtained
      under the effect of furazolidone.
AB  - Apathogenic Shigella flexneri 5a2c mutant treated with furazolidone can infect
      eucaryotic cells. These bacteria contain no virulence genes responsible for Sh.
      flexneri invasion, which seems to be the cause of their apathogenicity. The
      capacity of bacteria to penetrate into eucaryotic cells correlates with the
      appearance of ECP 32 protease specifically cleaving actin.

PMID- 15455124
TI  - Detection of mutant Mycoplasma hominis strains resistant to 16-membered macrolide
      antibiotic josamycin in clinical samples.
AB  - The incidence of point mutations responsible for josamycin resistance was studied
      by PCR in 48 strains of M. hominis isolated from patients with bacterial
      vaginosis. Mutant M. hominis strains were detected in 48% cases.

PMID- 15455125
TI  - Regulation of ceruloplasmin gene in mammals.
AB  - A site of rat DNA (about 1800 b. p.) adjacent to the first ceruloplasmin gene
      contains, apart from regulatory sequences common for all eukaryotic promotors,
      cis-elements, which are potential binding sites for soluble nuclear receptors of
      some hormones. Sequences characteristic of genes expressed in liver cells and
      mammary gland cells during lactation were detected. Full-length fragment of this
      locus of ceruloplasmin gene (1800 b. p.) was synthesized by PCR and used in gel
      shift experiments. It was found that soluble proteins extracted from purified
      nuclei of mammary gland cells during lactation and from the liver of adult and
      newborn rats, contain proteins specifically interacting with the PCR product. A
      fragment of chromosome gene containing exons encoding the central part of rat
      ceruloplasmin was cloned in pTZ19 bacterial vector. Gel shift assay showed that
      the cloned fragment contained binding sites for specific transcription factor
      YY1, whose level in nuclear protein fractions varied during ontogeny (according
      to immunoblotting data). Monoclonal antibodies detected protein YY1 in the
      complex of cloned DNA-nuclear proteins. Possible mechanisms of tissue-specific
      regulation of ceruloplasmin gene varying during ontogeny are discussed.

PMID- 15455126
TI  - Adjuvant effect of high-frequency hyperthermia of the abdominal cavity on the
      course of transplanted leukemia in AKR mice.
AB  - The adjuvant effect of high-frequency hyperthermia of the abdominal cavity was
      studied in 2-month-old mice of highly leukemic AKR strain treated with
      cyclophosphamide. Weights of organs, parameters of the peripheral blood, and
      cytological imprints of organs were compared in experimental and control animals.
      A more pronounced antitumor effect was observed in animals exposed to
      hyperthermia. These data provide the basis for clinical use of hyperthermia of
      the abdominal cavity.

PMID- 15455127
TI  - Cross reactivity of T cell receptor on memory CD8+ cells isolated after
      immunization with allogeneic tumor cells.
AB  - Experiments on mice deficient in expression of class I major histocompatibility
      complex molecules showed that memory CD8+ cells recognizing the alloantigen by
      the direct allogeneic recognition mechanism selectively proliferated in response
      to heated allogeneic cells. Adoptive transfer of memory cells from mice
      expressing green fluorescent protein transgene to wild-type animals showed for
      the first time that long-living memory cells suppress the response of naive T
      cells and abolish their involvement in the pool of memory cells. The pool of long
      living memory T cells was obtained in vitro with heated allogeneic stimulators.
      Apart from immunizing alloantigen, this clone recognized foreign molecules of the
      major histocompatibility complex. Cloning and sequencing of rearranged regions in
      memory T cells showed that two alpha-chains and one functional beta-chain are
      rearranged in cells of this pool. Only one alpha-chain was capable of forming
      protein product, which determines expression of only one form of T cell receptor.
      Experimental data directly confirm the hypothesis about degeneracy of recognition
      of allelic products of major histocompatibility complex molecules by T cell
      receptors. Suppression of the response of naive cells by memory cells probably
      underlies a previously unknown type of polarization of the immune response and
      determines clonal dominance and peripheral selection of T lymphocytes.

PMID- 15455128
TI  - Electromagnetic oscillations as a factor modulating blood neutrophil function.
AB  - Effects of various physical factors of electromagnetic nature on the synthetic
      and phagocytic activities of neutrophils were studied in vitro on the blood of
      patients with breast cancer. We found that alternating magnetic field, low
      intensity laser, photodiod radiation, and their combinations induced mobilization
      of blood neutrophil function.

PMID- 15455129
TI  - Peptide promotes overcoming of the division limit in human somatic cell.
AB  - We previously showed that treatment of normal human diploid cells with Epithalon
      (Ala-Glu-Asp-Gly) induced expression of telomerase catalytic subunit, its
      enzymatic activity, and elongation of telomeres. Here we studied the effect of
      this peptide on proliferative potential of human fetal fibroblasts. Primary
      pulmonary fibroblasts derived from a 24-week fetus lost the proliferative
      potential at the 34th passage. The mean size of telomeres in these cells was
      appreciably lower than during early passages (passage 10). Addition of Epithalon
      to aging cells in culture induced elongation of telomeres to the size comparable
      to their length during early passages. Peptide-treated cells with elongated
      telomeres made 10 extra divisions (44 passages) in comparison with the control
      and continued dividing. Hence, Epithalon prolonged the vital cycle of normal
      human cells due to overcoming the Heyflick limit.

PMID- 15455130
TI  - Effect of epithalamin on circadian relationship between the endocrine function of
      the thymus and melatonin-producing function of the pineal gland in elderly
      people.
AB  - The effect of epithalamin on circadian rhythms of thymic serum factor titers and
      melatonin concentrations in the blood of elderly people was studied. Course
      treatment with epithalamin modulated the rhythm of the thymic endocrine function.
      The increase in the titer of thymic serum factor at night coincided with the
      increase in blood melatonin concentration and shift of its acrophase to 3.00,
      which was characteristic of young people. In elderly people with preserved
      nocturnal peak of the thymic serum factor titer before therapy the nocturnal
      (3.00) concentration of melatonin was high and did not change after drug therapy.
      The correlation between melatonin concentration and titer of thymic serum factor
      increased after epithalamin treatment.

PMID- 15455131
TI  - Effects of bioactive factors of the pineal gland on thymus function and cell
      composition of the bone marrow and spleen in mice of different age.
AB  - The effects of factors from the pineal gland on the titer of thymic serum factor
      in the supernatant of 3-h thymus stroma cultures, number of stromal precursor
      fibroblasts and CD4+ cells in the bone marrow, and CD8+ cells in the spleens of
      adult and old CBA mice were studied in vitro. Epithalamin, Epithalon, and
      melatonin appreciably increased the titer of thymic serum factor in the
      supernatant of thymus stroma cultures from mice of different age and increased
      the percentage of CD4+ cells in the bone marrow suspension from old animals in
      vitro. The percentage of CD8+ lymphocytes decreased after incubation of splenic
      cells from old mice with melatonin. The percentage of bone marrow fibroblast
      precursor cells from adult and old mice did not appreciably change after
      incubation with the preparations.

PMID- 15455132
TI  - Structural organization of the basal layer and morphofunctional characteristics
      of mouse epidermal cambial cells.
AB  - The basal layer of mouse skin epidermis consists of special structures - rosettes
      functionally arranged in zones including about 20 rosettes. The rosette contains
      a central cambial cell; after division of this cell the mother cell remains in
      the center of the rosette and the daughter cell migrated to the center of a free
      rosette. The mother and daughter cells are dipole cells (sources of electric
      field). If the disposition of mother cells is unidirectional and they predominate
      over daughter cells, the latter cells transform into other cells, i. e. are
      differentiated.

PMID- 15455133
TI  - Nitroxide synthase activity as a marker of early stages of experimental cartilage
      dysmetabolism.
AB  - Time course of nitroxide synthase activity in the knee joint cartilage was
      studied in animals with experimental anterior instability of the knee joint. A
      significant increase in nitroxide synthase activity in chondrocytes was
      paralleled by a progressive decrease in glycosaminoglycan content in the
      cartilaginous matrix and subsequent destruction of the cartilage
      cytoarchitectonics.

PMID- 15455134
TI  - Transplantation of human embryonic myoblasts and bone marrow stromal cells into
      skeletal muscle of C57BL/10J-mdx mice.
AB  - We studied expression of dystrophin in skeletal muscles of C57BL/10J-mdx mice
      after transplantation of human embryonic and fetal myoblasts and bone marrow
      stromal cells. Dystrophin-positive areas corresponding to the location of
      transplanted cell were detected in muscles of all recipient mice after
      transplantation of different cell cultures, but the distribution of dystrophin
      characteristic of normal muscle fibers was detected only after transplantation of
      embryonic myoblasts. Dystrophin distribution in muscle fibers after
      transplantation of fetal myoblasts and bone marrow stromal cells was atypical.

PMID- 15455135
TI  - Analysis of tensiograms of cerebrospinal fluid with a kinetic model.
AB  - We develop a model for estimation of the parameters of dynamic tensiometry of
      biological fluids based on equations of formal chemical kinetics. The model
      considers diffusion of low- and high-molecular compounds and conformational
      restructuring of these compounds in the surface layer. This model was tested on
      cerebrospinal fluid from patients with meningitis. Some correlations between the
      parameters of tensiometric curves and protein, chloride, neutrophil, and
      lymphocyte content in the liquor are detected.

PMID- 15455136
TI  - Deoxyribozymes: DNA catalysts for bioorganic chemistry.
AB  - Deoxyribozymes are DNA molecules with catalytic activity. For historical and
      practical reasons, essentially all reported deoxyribozymes catalyze reactions of
      nucleic acid substrates, although this is probably not a fundamental limitation.
      In vitro selection strategies have been used to identify many deoxyribozymes that
      catalyze RNA cleavage, RNA and DNA ligation, and a variety of covalent
      modification reactions of nucleic acid substrates. Many deoxyribozymes are
      capable of catalysis with substantial rate enhancements reaching up to 10(10)
      fold over background, and their very high selectivities would often be difficult
      or impossible to achieve using traditional organic synthesis approaches. This
      report summarizes the current utility and potential future applications of
      deoxyribozymes from the bioorganic chemistry perspective.

PMID- 15455137
TI  - Nature's many mechanisms for the degradation of oligosaccharides.
AB  - Recent work on the mechanistic elucidation of the polysaccharide lyases, the
      [small alpha]-1,4-glucan lyases, and the Family 4 glycosidases have demonstrated
      that nature has evolved to use elimination steps for the degradation of
      oligosaccharides. The polysaccharide lyases (E.C. 4.2.2.-) have been shown to
      cleave uronic acid-containing polysaccharides via a stepwise E1cB mechanism. The
      mechanism of the alpha-1,4-glucan lyases (E.C. 4.2.2.13) is similar to the Family
      31 glycosidases, forming a covalent glycosyl-enzyme intermediate, which is
      subsequently cleaved by an E1-like E2 mechanism. Meanwhile, the Family 4
      glycosidases (E.C. 3.2.1.6) are suggested to undergo an oxidation-elimination
      addition-reduction sequence. These three groups of enzymes are examples of stark
      contrast to the vast number of well-characterized glycosidases (E.C. 3.2.1.-),
      which utilize either the direct or double displacement mechanisms as proposed by
      Koshland over 50 years ago.

PMID- 15455138
TI  - Cryoprobe 3D NMR of acetylated ball-milled pine cell walls.
AB  - 3D NMR of solubilized ball-milled pine cell walls reveals striking details of
      lignin units, right down to differentiating stereoisomers in the polymer. Such 3D
      spectral editing therefore overcomes the need to isolate wall components to study
      their structures.

PMID- 15455139
TI  - Electrochemical quantification of high-affinity halide binding by a steroid-based
      receptor.
AB  - The strength of binding between a cholapod receptor and halide anions is
      quantified using voltammetry at the liquid/liquid interface, revealing very high
      affinities and size-selectivity peaking at chloride.

PMID- 15455140
TI  - Tetracyanoresorcin[4]arene as a pH dependent artificial acetylcholine receptor.
AB  - This communication describes the facile synthesis of tetracyanoresorcin[4]arene
      and its high and pH dependent affinities toward biologically important
      acetylcholine in the physiological pH region.

PMID- 15455141
TI  - Bromine catalyzed conversion of S-tert-butyl groups into versatile and, for self
      assembly processes accessible, acetyl-protected thiols.
AB  - The facile and efficient conversion of a tert-butyl protecting group to an acetyl
      protecting group for thiols by catalytic amounts of bromine in acetyl chloride
      and the presence of acetic acid has been developed. The fairly mild reaction
      conditions are of particular interest for new protecting group strategies for
      sulfur functionalised target structures.

PMID- 15455142
TI  - A simple solid phase diversity linker strategy using enol phosphonates.
AB  - Polymer bound lactam enol phosphonates can be easily generated using simple
      phenol on polystyrene resin. These stable, storable compounds can be released in
      a diversity cleavage strategy, using Suzuki cross coupling conditions, to provide
      2-arylenamides in moderate to good overall yields.

PMID- 15455143
TI  - The first Cu(I)-mediated nucleophilic trifluoromethylation reactions using
      (trifluoromethyl)trimethylsilane in ionic liquids.
AB  - The new ionic liquids (5a-8a) were used as reaction media for nucleophilic
      trifluoromethylation reactions of trifluoromethyl(trimethyl)silane with (1) aryl,
      allyl, benzyl, and alkyl halides in Cu(I)-mediated C-C bond formation reactions,
      and (2) carbonyl functionalities catalyzed with Ph3P or CsF. In addition,
      conversion of benzyl bromide as a model compound to benzyl fluoride was examined
      in using 6a CsF as the fluorinating reagent. The morpholinium-based ionic liquid
      (6a) stood out as an efficient solvent system comparable to organic solvents and
      superior to the other new ionic liquids prepared in this work as well as to
      [bmim]+[PF6]-. Neat reactions of N-methyloxazolidine (1), N-methylmorpholine (2),
      N-methylimidazole (3) or N-methyltriazole (4) with 2-(2-ethoxyethoxy)ethyl
      bromide (BrCH2CH2OCH2CH2OCH2CH3, ) or 2-bromoethyl methyl ether (BrCH2CH2OCH3,
      10) at 75 or 105 degrees C gave the N-(2-ethoxyethoxy)ethyl- or N-methoxyethyl
      substituted oxazolidinium, morpholinium, imidazolium and triazolium quaternary
      bromides (1a-4a, 1b-4b) which were metathesized with LiN(SO2CF3)2 to form the
      respective room-temperature liquid bis(trifluoromethanesulfonyl)amides 5a-8a and
      5b-8b in high yields with transition or melting points < -78 degrees C as
      determined by DSC. All of the ionic liquids are thermally stable to > 310 degrees
      C as determined by thermogravimetric analyses (TGA). Densities range between 1.29
      and 1.53 g cm(-3) at 25 degrees C.

PMID- 15455144
TI  - Design, synthesis, biological activity and structural analysis of cyclic peptide
      inhibitors targeting the substrate recruitment site of cyclin-dependent kinase
      complexes.
AB  - Inhibition of cyclin A- and cyclin E-associated cyclin-dependent kinase-2 (CDK2)
      activities is an effective way of selective induction of apoptotic cell death via
      the E2F pathway in tumour cells. The cyclin groove recognition motif (CRM) in the
      natural CDK-inhibitory (CDKI) tumour suppressor protein p27KIP1 was used as the
      basis for the design and synthesis of a series of cyclic peptides whose
      biological activity and structural characterisation by NMR and X-ray
      crystallography is reported. Whereas linear p27KIP1 sequence peptides were
      comparatively ineffective, introduction of side chain-to-tail constraints was
      found to be productive. An optimal macrocyclic ring size for the conformational
      constraint was determined, mimicking the intramolecular H-bonding system of p27.
      Molecular dynamics calculations of various macrocycles suggested a close
      correlation between ring flexibility and biological activity. Truncated inhibitor
      peptide analogues also confirmed the hypothesis that introduction of a cyclic
      conformational constraint is favourable in terms of affinity and potency. The
      structural basis for the potency increase in cyclic versus linear peptides was
      demonstrated through the determination and interpretation of X-ray crystal
      structures of complexes between CDK2/cylin A (CDK2A) and a constrained
      pentapeptide.

PMID- 15455145
TI  - Dissociative electron transfer to and from pyrimidine cyclobutane dimers: an
      electrochemical study.
AB  - Cyclic voltammetry was used to study the reduction and oxidation behaviour of
      several pyrimidine cyclobutane dimers mimicking UV induced lesion in DNA strands
      in polar solvents (N,N-dimethylformamide and acetonitrile). Both electron
      injection and removal to and from the dimers, respectively, lead to their
      cleavage and reformation of the monomeric base. The influence of stereochemistry
      and substitution pattern at the cyclobutane motif on the reactivity has been
      studied. It appears that the repair process always proceeds in a sequential
      fashion with initial formation of a dimer ion radical intermediate, which then
      undergoes ring opening by homolytic cleavage of the two C-C bonds. Standard redox
      potentials for the formation of both radical anion and radical cation state of
      the dimers were determined. Quantum calculations on simplified model compounds
      reveal the reason for the finding that the exergonic homolytic cleavages of the
      carbon-carbon bonds are endowed with sizeable activation barriers. The
      consequences of these mechanistic studies on the natural enzymatic repair by
      photolyase enzyme are discussed.

PMID- 15455146
TI  - [2]Rotaxanes containing pyridinium-phosphonium axles and 24-crown-8 ether wheels.
AB  - A triethylphosphonium group attached to a pyridinium ethane moiety can be used as
      an axle for the self-assembly of [2]pseudorotaxanes and [2]rotaxanes. Although
      [2]pseudorotaxane formation is limited due to the bulk of the PR4+ group,
      [2]rotaxanes can be formed utilising 24-crown-8 ether, benzo-24-crown-8 ether and
      naphtho-24-crown-8 ether. The synthesis of these [2]rotaxanes and the X-ray
      structure of the [2]rotaxane containing a 24-crown-8 ether wheel are described.
      When the crown ether contains an aromatic group two possible conformational
      isomers exist; these are identified at low temperature by 1H and 31P NMR
      spectroscopy.

PMID- 15455147
TI  - Monomeric analogues of halocidin.
AB  - Halocidin is a heterodimeric antimicrobial peptide isolated from a tunicate,
      Halocynthia aurantium. We used the most active of the two monomers, an 18 residue
      amidated peptide, as lead structure and determined the role of each amino acid
      with alanine scanning. The results obtained led to the synthesis of a first
      generation of analogues with antimicrobial activity. The selectivity towards
      bacterial versus mammalian cells has been explored, as well as the specificity
      for gram positive (Staphylococcus aureus ATCC 25923) versus gram negative
      bacteria (Escherichia coli ATCC 25922). GRAVY (grand average of hydropathicity)
      was used to analyze the results.

PMID- 15455148
TI  - Asymmetric synthesis of the cis- and trans-stereoisomers of 4-aminopyrrolidine-3
      carboxylic acid and 4-aminotetrahydrofuran-3-carboxylic acid.
AB  - The diastereoselective conjugate addition of lithium (S)-N-benzyl-N-[small alpha]
      methylbenzylamide has been successfully applied to the first asymmetric syntheses
      of cis-(3S,4R)- and trans-(3R,4R)-4-aminotetrahydrofuran-3-carboxylic acids (26%
      and 25% overall yield respectively, >98% d.e. and >97% e.e. in each case).
      Furthermore, the most efficient asymmetric synthesis to date of cis-(3R,4R)- and
      trans-(3R,4S)-4-aminopyrrolidine carboxylic acids is delineated: for cis-(3R,4R),
      four steps, >98% d.e., 52% overall yield; for trans-(3R,4S), five steps, >98%
      d.e., 50% overall yield.

PMID- 15455149
TI  - Stereoselective synthesis and structure of butalactin and lactone II isolated
      from Streptomyces species.
AB  - Butalactin (1a) and lactone II (2a) have been synthesized starting from (S)-malic
      acid and sorbic acid by a straightforward route. The absolute stereochemistry of
      1a and 2a was unambiguously established by this synthesis.

PMID- 15455150
TI  - Synthesis and binding properties of calix[4]arenes with [2 + 2'] mixed ligating
      functional groups.
AB  - A series of mixed [2 + 2'] p-tert-butylcalix[4]arene have been synthesised by
      selective 1,3-dialkylation of phenolic groups using various alkylating agents
      such as benzyl bromide, methyl iodide, ethyl bromoacetate, and 2-methoxyethyl
      tosylate. The extraction and complexation properties of the synthesized
      calixarenes towards alkali and alkaline earth metal cations have been
      investigated in acetonitrile by means of UV spectrophotometry and 1H NMR
      spectroscopy. The results show the formation of ML and/or ML2 species depending
      on the ligand and the cation. The enthalpies and entropies of complexation of
      alkali metal cations by a tetraglycol, diglycol-dibenzyl and diglycol-diester
      derivatives have been obtained from calorimetric measurements. The results
      revealed that the formation of ML species is controlled by enthalpy while the
      formation of ML2 from ML is entropy driven.

PMID- 15455151
TI  - Oligonucleotides with 2'-O-carboxymethyl group: synthesis and 2'-conjugation via
      amide bond formation on solid phase.
AB  - An efficient method for synthesis of oligonucleotide 2'-conjugates via amide bond
      formation on solid phase is described. Protected oligonucleotides containing a 2'
      O-carboxymethyl group were obtained by use of a novel uridine 3'phosphoramidite,
      where the carboxylic acid moiety was introduced as its allyl ester. This
      protecting group is stable to the conditions used in solid-phase oligonucleotide
      assembly, but easily removed by Pd(0) and morpholine treatment. 2'-O
      Carboxymethylated oligonucleotides were then efficiently conjugated on a solid
      support under normal peptide coupling conditions to various amines or to the N
      termini of small peptides to give products of high purity in good yield. The
      method is well suited in principle for the preparation of peptide-oligonucleotide
      conjugates containing an amide linkage between the 2'-position of an
      oligonucleotide and the N-terminus of a peptide.

PMID- 15455152
TI  - Photomodulation of ionic current through hemithioindigo-modified gramicidin
      channels.
AB  - Incorporation of photo-switchable amino acids into peptides and proteins offers
      prospects for the control of complex biochemical processes using light.
      Currently, only a few photo-switchable amino acids are known. We report the
      design and synthesis of a novel hemithioindigo-based amino acid and its
      incorporation into the model ion channel gramicidin. Photoisomerization of the
      hemithioindigo moiety between E and Z isomeric forms is shown to modulate ionic
      current through the channel in a predictable way. This new amino acid thus
      expands the possibilities for photo-control in diverse systems.

PMID- 15455153
TI  - Multistate properties of 7-(N,N-diethylamino)-4'-hydroxyflavylium. An example of
      an unidirectional reaction cycle driven by pH.
AB  - The synthetic flavylium salt 7-(N,N-diethylamino)-4'-hydroxyflavylium
      tetrafluoroborate gives rise in aqueous solution to a complex network of chemical
      reactions driven by pH. The system was studied by 1H NMR, single crystal X-ray
      diffraction, steady state and transient UV-Vis spectrophotometry as well as
      stopped flow. The crystal structure shows a high degree of coplanarity between
      the pyrylium system and the phenyl group in position 2. Thermodynamic and kinetic
      constants for the pH dependent network of chemical reactions were obtained. The
      introduction of an amino group in position 7 allows formation of protonated
      species leading, in particular, to a tautomeric form of the protonated cis
      chalcone, H+, whose absorption spectra is rather red shifted, in comparison with
      the correspondent protonated trans-chalcone, H+. The H+ species can be rapidly
      converted into the flavylium cation through a first order process with lifetime
      of 0.2 s at pH = 2.35. This new reaction channel confers this compound a peculiar
      behaviour in acidic media, allowing to define an unidirectional pH driven
      reaction cycle.

PMID- 15455154
TI  - Thiazolidin-4-one formation. Mechanistic and synthetic aspects of the reaction of
      imines and mercaptoacetic acid under microwave and conventional heating.
AB  - Microwave irradiation of a mixture of benzylidene-anilines and mercaptoacetic
      acid in benzene gives 1,3-thiazolidin-4-ones in very high yield (65-90%), whereas
      the same reaction performed through using the conventional method, at reflux
      temperature, requires a much longer time and gives a much lower yield (25-69%).
      This difference seems to be due to some intermediates and by-products formed
      during the conventional reaction. On the basis of 1H NMR studies, two different
      mechanisms, acting in benzene and in DMF, respectively, have been hypothesized
      for the thiazolidin-4-one system formation.

PMID- 15455155
TI  - Effect of chain length on transfection properties of spermine-based gemini
      surfactants.
AB  - The synthesis and associated structure-activity relationships for gene
      transfection of a series of spermine-derived cationic gemini surfactants
      incorporating diamino acid headgroups and either identical (symmetrical) or
      different (unsymmetrical) lipophilic tailgroups is described. Transfection
      activity is found to depend critically upon the structural elements present.

PMID- 15455156
TI  - On the structure of carotenoid iodine complexes.
AB  - Previous work on carotenoid-iodine complexes is briefly reviewed. The formation
      of iodine complexes of beta,beta-carotene and of (3R,3' R )-beta,beta-carotene
      3,3'-diol (zeaxanthin) has been studied by modern methods including UV/VIS/NIR,
      IR MS, EPR, ENDOR and NMR (1H, 1H-1H COSY, TOCSY, 2D ROESY, 1H-13C HSQC and 1H
      13C HMBC) spectroscopy, and chemical reactions monitored by HPLC, TLC and
      spectral analysis (VIS, MS, 1H NMR). beta,beta-Carotene formed a solid complex
      C40H56 x 4I with iodine in hexane and a solvent complex with lambdamax 1010 nm in
      chlorinated solvents. Iodine was not covalently bound to the carotene.
      Spectroscopic and chemical evidence is consistent with the representation of the
      beta,beta-carotene-iodine complex containing iodine in a pi complex with
      cationic/radical cationic properties. Extensive E/Z isomerisation was noted for
      all quenching products obtained in acetone, with thiosulfate, by dilution, or by
      reaction with nucleophile (MeOH). Key products obtained from the beta,beta
      carotene-iodine complex were 4',5'-didehydro-4,5'-retro-beta,beta-carotene
      (isocarotene) and 4-methoxy-beta,beta-carotene. The zeaxanthin-iodine complex was
      not suitable for a practical synthesis of (3S,3'S)-4',5'-didehydro-4,5'-retro
      beta,beta-carotene-3,3'-diol (eschscholtzxanthin).

PMID- 15455157
TI  - Sensing of remote oxyanion binding at the DNA binding domain of the molybdate
      dependent transcriptional regulator, ModE.
AB  - The molybdate-dependent transcriptional regulator ModE of Escherichia coli
      displays a large (50%) quenching of its intrinsic tryptophan fluorescence on
      binding molybdate. The changes in fluorescence have been exploited to analyse the
      binding of molybdate to ModE. Utilising site-directed mutagenesis, a series of
      phenylalanine substitutions for the three tryptophans of ModE (Trp49, Trp131 and
      Trp186) have been constructed, to yield three mono-Trp-containing derivatives.
      This has allowed an assessment to be made of the contribution of each of the
      three tryptophans to the spectral changes observed on binding molybdate; these
      are most distinctive for Trp186. Linkage between the DNA-binding and molybdate
      binding sites (some 55 angstroms apart) is shown by (a) the small, but definite,
      effect of molybdate on the fluorescence of Trp49 which is located at the DNA
      binding winged helix-turn-helix domain, and (b) the finding that the binding of
      either ligand is enhanced in the presence of the other. The studies demonstrate
      that the mono-Trp derivatives of ModE could be useful tools with which to study
      the signal transduction processes specifically associated with molybdate
      dependent transcriptional regulation and that this approach may have wider
      implications for analysis of other regulated systems.

PMID- 15455158
TI  - Halogenated 7-deazapurine nucleosides: stereoselective synthesis and conformation
      of 2'-deoxy-2'-fluoro-beta-D-arabinonucleosides.
AB  - The stereoselective syntheses of 5-halogenated 7-(2-deoxy-2-fluoro-beta-D
      arabinofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine nucleosides 3b-d, 4a-c as well as 7
      deaza-2'-deoxyisoguanosine are described. Nucleobase anion glycosylation of 2
      amino-4-chloro-7H-pyrrolo[2,3-d]pyrimidine (5) with 3,5-di-O-benzoyl-2-deoxy-2
      fluoro-alpha-D-arabinofuranosyl bromide (6) exclusively gave the beta-D-anomer,
      which was deblocked (--> 8), aminated at C4 (--> 3a) and selectively deaminated
      at C2 to yield 2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl 7-deazaisoguanine (2).
      Condensation of the 5-halogenated 4-chloro-2-pivaloylamino-7H-pyrrolo[2,3
      d]pyrimidines 9a-c with 6 furnished the N7-nucleosides 10a-c together with N2,N7
      bisglycosylated compounds 11a-c. The former was converted to the corresponding
      2,4-diamino-compounds 3b-d, and the latter was deblocked by NaOMe/MeOH to yield
      the 4-methoxy-nucleosides 4a-c. Conformational analysis of the sugar moiety of
      the nucleosides 2 and 3a-d was performed on the basis of vicinal [1H,1H] coupling
      constants. The fluorine atom in the sugar moiety shifts the sugar conformation
      from S towards N by about 10%, while the halogen substituents in the base moiety
      increase the hydrophobicity and polarizability of the nucleobases.

PMID- 15455159
TI  - Loops on loops: generation of complex scaffolded peptides presenting multiple
      cyclic fragments.
AB  - Scaffolded peptides presenting two different cyclic peptide fragments through a
      cyclic peptidomimetic scaffold in a site-selective fashion, were generated by
      stepwise solid phase synthesis and fragment condensation in parallel,
      demonstrating that either strategy is adequate to generate complex scaffolded
      peptides.

PMID- 15455160
TI  - Nonameric porphyrin assemblies--formation and intra-assembly energy transfer
      reactions.
AB  - The nonameric porphyrin assemblies constructed with the series of free base
      tetraphenylporphyrins Pn having four pyrazine moieties linked with alkyl chains
      of different lengths, (CH2)n (n = 1, 5, 9, 17, 30), and dimeric [meso-tetrakis(2
      carboxy-4-nonylphenyl)porphyrinato]zinc(II), ZnP2, show the effective light
      collection effect and the typical Forster-type energy transfer from ZnP2 to Pn.

PMID- 15455161
TI  - Combinatorial synthesis of benztropine libraries and their evaluation as
      monoamine transporter inhibitors.
AB  - A combinatorial synthesis of benztropine analogues is presented. Radical
      azidonation of 3-benzyloxy-8-azabicyclo[3.2.1]octane-8-carboxylic acid tert-butyl
      ester 3 to 3-(1-azidobenzyloxy)-8-azabicyclo[3.2.1]octane-8-carboxylic acid tert
      butyl ester 4 was used as a key step in the synthesis. This step was optimized by
      adding 10% DMF to the reaction. Reaction of 4 with phenyl magnesium bromide
      followed by Boc removal and N-methylation gave benztropine 1. Reaction of five
      component Grignard reagents with 4 was used to create a two-dimensional library
      of 25 N-normethylbenztropine analogues. Further reaction of this library with
      five alkyl bromides was carried out to create a three-dimensional library
      containing 125 compounds. Screening of the libraries towards binding and
      inhibition of uptake of the human dopamine (hDAT), serotonin (hSERT) and
      norepinephrine transporters (hNET) was carried out. None of the synthesized
      compounds were found to be stronger than benztropine, and none were selective for
      inhibition of binding over monoamine uptake.

PMID- 15455162
TI  - Attempted reduction of 1,2,3-thiadiazole-4-carboxylates with samarium/iodine in
      methanol. Unexpected ring enlargement to 1,2,5-trithiepan-4,6-dicarboxylates.
AB  - When stirred with powdered samarium and iodine in methanol at ice-cold
      temperature, ethyl 1,2,3-thiadiazole-4-carboxylate 5 underwent unusual reduction
      involving the dimeric ring enlargement with a sulfur addition, giving dimethyl
      1,2,5-trithiepan-4,6-dicarboxylates 7a,b as a cis/trans-isomeric mixture in
      acceptable yield. The 1,2,3-thiadiazole ring of 5 proved to resist reduction by
      ordinary reducing agents, where the only choice in most cases was either recovery
      of the unchanged substrate or decomposition to an intractable mixture of
      unidentified products and tar.

PMID- 15455163
TI  - Evaluation of alternative approaches for the synthesis of macrocyclic
      bisindolylmaleimides.
AB  - Approaches for the synthesis of macrocyclic bisindolylmaleimides, in which the
      indole nitrogens are linked with a tether, are described. Two alternative
      approaches were investigated: macrocyclisation in either the 'southern' (by
      adding the tether to the bisindolylmaleimide ring system) or the 'northern'
      district. With two-, three- and four-atom tethers, both of these approaches were
      unsuccessful for a wide range of attempted macrocyclisation reactions (palladium
      catalysed pi-allyl substitution, ring-closing metathesis, McMurry reaction,
      iodocyclisation, formation of a silylene derivative, substitution of an
      alpha,omega-disubstituted electrophile). The failure of all of these reactions
      was ascribed to the strained nature of the target ring system. However, with
      longer tethers (six to ten atoms), the macrocycles could prepared using either a
      ring-closing metathesis reaction or by substitution of an alpha,omega-dibromide).
      Fourteen successful macrocyclisation reactions are described; deprotection gave
      eleven macrocyclic bisindolylmaleimides in which an imide substituent had been
      removed.

PMID- 15455164
TI  - The future is near: focus on myopia.

PMID- 15455165
TI  - Biostatistics 301A. Repeated measurement analysis (mixed models).

PMID- 15455166
TI  - Chronic cough in children.
AB  - Chronic cough, defined as coughing for more than four weeks, is a common
      childhood complaint. With careful history-taking and appropriate investigations,
      a single cause can be found in most cases--these can be successfully treated.
      Although we have some understanding about the cough reflex through animal
      studies, the full mechanism and exact location of the responsible neurons in the
      human brain have not been completely elucidated. There are many causes for it but
      asthma, chronic rhinosinusitis and gastroesophageal reflux disease account for
      most of the cases. Other causes, such as dysfunctional swallowing, congenital
      anomalies and cigarette smoking, are also important. All children with chronic
      cough deserve a thorough and proper evaluation. The current review provides
      essential information for medical practitioners to approach this problem. An
      algorithm is provided to aid the diagnostic process.

PMID- 15455167
TI  - Refractive errors in medical students in Singapore.
AB  - INTRODUCTION: Refractive errors are becoming more of a problem in many societies,
      with prevalence rates of myopia in many Asian urban countries reaching epidemic
      proportions. This study aims to determine the prevalence rates of various
      refractive errors in Singapore medical students. METHODS: 157 second year medical
      students (aged 19-23 years) in Singapore were examined. Refractive error
      measurements were determined using a stand-alone autorefractor. Additional
      demographical data was obtained via questionnaires filled in by the students.
      RESULTS: The prevalence rate of myopia in Singapore medical students was 89.8
      percent (Spherical equivalence (SE) at least -0.50 D). Hyperopia was present in
      1.3 percent (SE more than +0.50 D) of the participants and the overall
      astigmatism prevalence rate was 82.2 percent (Cylinder at least 0.50 D).
      CONCLUSION: Prevalence rates of myopia and astigmatism in second year Singapore
      medical students are one of the highest in the world.

PMID- 15455168
TI  - Comparison of effectiveness of vaginal and abdominal routes in treating severe
      uterovaginal or vault prolapse.
AB  - INTRODUCTION: This study compares the efficacy of abdominal and vaginal routes in
      correcting severe uterovaginal or vault prolapses by examining their primary
      surgical outcomes. METHODS: A retrospective study was conducted on operations
      performed from March 1998 to December 2001. The classifications of uterovaginal
      prolapse and vault prolapse were based on the Halfway system. It involved 177
      women with at least grade 4 uterovaginal prolapse or grade 3 vault prolapse, and
      had undergone vaginal sacrospinous ligament fixation or abdominal sacrocolpopexy.
      The subjects were divided into two groups: 113 women who had an abdominal
      sacrocolpopexy and 64 women who had a vaginal sacrospinous ligament fixation. The
      primary surgical outcome measures was classified as cured, improved or failure
      according to our definition at their last follow-up. RESULTS: The abdominal
      sacrocolpopexy group had significantly greater intra-operative blood loss,
      operating time, haematuria, longer postoperative catheterisation and
      hospitalisation. Vaginal sacrospinous ligament fixation had more suture erosion.
      95.6 percent of women with abdominal sacrocolpopexy were cured compared to 79.7
      percent with vaginal sacrospinous ligament fixation. Five (4.4 percent) patients
      in the abdominal sacrocolpopexy group and six (9.4 percent) in the vaginal
      sacrospinous ligament fixation group defaulted their six-month follow-up with a
      mean follow-up of 18.1 months (range 0.9-48.1 months) and 13.2 months (range 1.1
      29.1 months), respectively. CONCLUSION: Abdominal sacrocolpopexy is more
      effective in correcting severe uterovaginal or vault prolapses but it is
      associated with higher intra- and post-operative morbidity compared to vaginal
      sacrospinous ligament fixation. Vaginal sacrospinous ligament fixation is
      preferred in patients with medical disorders.

PMID- 15455169
TI  - Implant contraception in Singaporean women: one decade of experience in KK
      Women's and Children's Hospital.
AB  - INTRODUCTION: The aim of this study was to assess user acceptability and
      effectiveness of implant contraception in Singaporean women. METHODS: A
      prospective study was carried out on 553 patients who received Norplant implant
      in our hospital from 1 January 1992 to 31 December 2000, and followed-up till 15
      July 2003. The patients' profile, side-effects, satisfaction and continuation
      rate of Norplant implant were studied. RESULTS: The mean age of the subjects was
      29.4 (plus or minus 5.1) years. The mean parity was 2.1 (plus or minus 1) live
      births. More than one-half (55.2 percent) of the subjects had used other methods
      of contraception before. The main reason for them to switch to implant
      contraception was convenience (63.6 percent). Of the 516 users on follow-up, the
      common side-effects were menstrual irregularity (51 percent), secondary
      amenorrhoea (9.6 percent) and weight gain (15.7 percent). 29.3 percent of users
      did not experience any side-effect. There was only one contraceptive failure,
      which may be related to drug interaction. The Pearl Index was 0.054 per hundred
      women years. There was only one serious adverse event of a patient (0.2 percent)
      who developed severe hypertension requiring treatment. The continuation rate was
      92.4 percent after one year, 80.8 percent after two years, 68.9 percent after
      three years and 58.5 percent after four years. The main reasons for early implant
      removal were side-effects and desire for future pregnancy. Re-insertion was
      carried out in 53.7 percent of users who had completed five years of Norplant
      contraception. CONCLUSION: This largest sub-dermal hormonal implant contraception
      study in multi-racial Singapore showed that Norplant contraception had a high
      degree of effectiveness with relatively high user satisfaction and continuation
      rate.

PMID- 15455170
TI  - Unusual migratory foreign body in the neck.
AB  - Reports of ingested foreign bodies penetrating the pharynx and migrating through
      the neck are rare, and mostly involved fish bones. We describe a 44-year-old man
      who was involved in a motor vehicle accident and accidentally swallowed his
      tooth. The swallowed tooth penetrated the pharynx and became lodged adjacent to
      his right thyroid gland. It was successfully removed via neck exploration and the
      patient recovered well.

PMID- 15455171
TI  - C7 fracture treated with a pedicle screw system under navigation guidance.
AB  - A 51-year-old woman with traumatic fracture-subluxation of C6-C7 vertebrae was
      treated by pedicle screw fixation. Among several methods for surgical treatment
      of the cervical spine, this technique provides a more rigid anchor to prevent
      collapsing or instability of the spinal column, particularly at the
      cervicothoracic junction. However, the risk of injuring the adjacent
      neurovascular structures cannot be completely eliminated. The characteristics of
      the cervicothoracic junction, surgical approaches and pedicle screw fixation
      techniques are emphasised.

PMID- 15455172
TI  - The significance of cystic adrenal lesions in multiple endocrine neoplasia IIB
      syndrome.
AB  - Cystic adrenal lesions are common, but cystic pheochromocytomas are rare. In the
      setting of a cystic adrenal mass in a patient with multiple endocrine neoplasia
      syndrome (MEN) IIB, the diagnosis of pheochromocytoma must be considered. We
      report a 29-year-old woman with typical phenotype of MEN IIB (marfanoid habitus,
      thick blubbery lips, mucosal ganglioneuromas) and a history of medullary thyroid
      carcinoma. She presented with headaches, palpitations and tremors. Computed
      tomography revealed a left cystic adrenal mass. The likelihood of the lesion
      being a pheochromocytoma was thought to be low due to its cystic appearance.
      However, urine ephinephrine and metanephrine levels were elevated. She underwent
      a left adrenalectomy and histological examination revealed a cystic
      pheochromocytoma.

PMID- 15455173
TI  - A medical mystery. Lead poisoning.
AB  - A 25-year-old schizophrenic man presented with abdominal pain, nausea, vomiting,
      weight loss and anaemia. He was noted to be malnourished with generalised muscle
      atrophy. Laboratory investigations showed Hb 4.7 mmol/L, MCV 80fl, bilirubin 75
      micromol/L and reticulocyte count 93 percent. Peripheral blood films showed
      anisocytosis, basophilic stippling and Cabot's rings. Electromyography confirmed
      typical motor nerve neuropathy. The clinical and laboratory findings were that of
      lead poisoning. The patient was later found to be ingesting lead-containing
      paint. He was treated with lead-chelating agents.

PMID- 15455175
TI  - The epidemiology and prevention of drowning in Singapore.

PMID- 15455178
TI  - Absorption and metabolism of genistein and its five isoflavone analogs in the
      human intestinal Caco-2 model.
AB  - The purposes of this study were to determine the effect of structural change on
      the intestinal disposition of isoflavones and to elucidate the mechanisms
      responsible for transport of phase II isoflavone conjugates. Transport and
      metabolism of six isoflavones (i.e., genistein, daidzein, glycitein,
      formononetin, biochanin A, and prunetin) were studied in the human intestinal
      Caco-2 model and mature Caco-2 cell lysate. Glucuronides were the main
      metabolites in intact Caco-2 cells for all isoflavones except prunetin, which was
      mainly sulfated. In addition, the 7-hydroxy group was the main site for
      glucuronidation whereas the 4'-hydroxy group was only one of the possible sites
      for sulfation. Glucuronidated isoflavones (except biochanin A) were preferably
      excreted to the basolateral side, whereas sulfated metabolites (except genistein
      and glycitein) were mainly excreted into the apical side. Polarized excretion of
      most isoflavone conjugates was inhibited by the multidrug resistance-related
      protein (MRP) inhibitor leukotriene C(4) (0.1 micro M) and the organic anion
      transporter (OAT) inhibitor estrone sulfate (10 micro M). When formation and
      excretion rates of isoflavones were determined simultaneously, the results showed
      that formation served as the rate-limiting step for all isoflavone conjugates
      (both glucuronides and sulfates) except for genistein glucuronide, which had
      comparable excretion and formation rates. In conclusion, the intestinal
      disposition of isoflavones was structurally dependent, polarized, and mediated by
      MRP and OAT. Formation generally served as the rate-limiting step in the cellular
      excretion of conjugated isoflavones in the Caco-2 cell culture model.

PMID- 15455180
TI  - Asparaginase inhibition of adhesion of type 1-fimbriated and P-fimbriated
      Escherichia coli to epithelial cell receptors.
AB  - The 3D structures of Fim H and PapG proteins complexed with the host carbohydrate
      receptor demonstrate that both utilize binding-pocket asparagines for contact or
      stabilization with the carbohydrate. Pretreatment of whole bacteria with
      asparaginase resulted in decreased fimbriae-mediated attachment to urinary
      epithelial cells. Enzyme treatment of bacteria pre-adhered to epithelial cells
      removed more uropathogenic E. coli than the indigenous flora attached to them.

PMID- 15455181
TI  - Whom are we treating with lipid-lowering drugs? Are we following the guidelines?
      Evidence from a population-based study: the Tromso study 2001.
AB  - OBJECTIVE: The beneficial effect of lipid-lowering drugs (LLDs) is well
      documented. Despite increasing sales of LLDs, little is known about what
      characterizes LLD users. Our objective was to describe LLD users in a general
      population according to socio-demographic factors, cardiovascular risk factors
      and coronary heart disease (CHD), and to study the achievement of cholesterol
      treatment goals according to national guidelines. METHODS: The Tromso study is a
      population-based study of chronic diseases, risk factors and drug use in the
      municipality Tromso, in north Norway. The fifth survey was conducted in 2001 and
      included 7,973 men and women (attendance rate 78.1%). Self-reported use of LLDs
      and/or proprietary LLDs was included as LLD use in the analysis. RESULTS: LLD use
      was reported in 9.6% of all women and 14.0% of all men, of whom 36.5% achieved
      the nationally recommended lipid goal. Among individuals with CHD, 49.9% of all
      women and 55.4% of all men were LLD users. The individuals with a risk condition
      (hypertension and/or diabetes) and total cholesterol level above the target of
      5.0 mmol/l and the healthy individuals with total cholesterol level >/=8.0 mmol/l
      constituted 47.2% of the study population without CHD. In this group, which was
      eligible for primary prevention, 8.0% of the women and 7.4% of the men reported
      LLD use. CONCLUSIONS: Only half of all subjects with CHD were taking a LLD. The
      large discrepancy between national recommendations and actual LLD use in primary
      prevention should be addressed in future revisions of the guidelines.

PMID- 15455182
TI  - Diclofenac systemic exposure is not increased when topical diclofenac is applied
      to ultraviolet-induced erythema.
AB  - OBJECTIVES: Diclofenac is a non-steroidal anti-inflammatory drug used for a
      variety of painful and inflammatory conditions. A new low-dose, topical-gel form
      of diclofenac sodium (diclofenac-Na) has been developed for pain relief and
      redness reduction after sunburn. The objective was to compare exposure to oral
      diclofenac-Na with the systemic exposure to diclofenac after application of the
      new topical diclofenac-Na 0.1% Emulgel gel (diclofenac-Na gel) to normal skin and
      to that with ultraviolet-induced erythema relative. METHODS: This study was an
      open, single-centre, three-period, non-randomised trial in 18 healthy Caucasian
      subjects. During the first period, 12.5 g gel (12.5 mg diclofenac-Na) was applied
      twice on a single day to normal skin. During the second period, a 25-mg
      diclofenac-Na, enteric-coated tablet was given orally three times in a single
      day. During the third period, the diclofenac-Na gel was applied, as in the first
      period, but during the early phase of an erythema induced by three times the
      ultraviolet minimal erythema dose, i.e. a first-degree sunburn associated with
      pain. During each period, venous blood samples were collected over 24 h and urine
      was collected over 72 h after first administration for the determination of
      diclofenac in plasma and urine and of 4'-OH-diclofenac in urine. RESULTS: The
      systemic exposure after topical application of 25 mg diclofenac-Na on sunburned
      skin was less than 3% that of 75 mg oral diclofenac-Na and was not increased to
      that measured on normal skin. CONCLUSION: The diclofenac-Na 0.1% Emulgel gel can
      be applied safely to sunburned skin (superficial sunburn, i.e. first degree) as
      well as to normal skin.

PMID- 15455183
TI  - Relationships between the changes of serum levels of OPG and RANKL with age,
      menopause, bone biochemical markers and bone mineral density in Chinese women
      aged 20-75.
AB  - The correlations between the serum levels of OPG, RANKL with age, menopause, bone
      markers, and bone mineral densities (BMDs) at the lumbar spine and proximal femur
      were studied in 504 pre- and postmenopausal Chinese women aged 20-75 years. We
      found that age was positively and negatively correlated with serum concentrations
      of OPG (r = 0.442, P < 0.001) and RANKL (r = -0.263, P < 0.001), respectively.
      Compared with premenopausal women, postmenopausal women showed higher serum OPG
      levels (107.6 +/- 3.0 vs 72.0 +/- 1.8 pg/ml, P < 0.001), lower serum RANKL
      concentrations (4.7 +/- 0.4 vs. 5.8 +/- 0.3 pg/ml, P < 0.001) and RANKL/OPG
      ratios (0.045 +/- 0. 004 vs. 0.099 +/- 0.008, P < 0.001). Neither serum levels of
      OPG nor RANKL or RANKL/OPG ratio correlated with BMDs after adjustment of age and
      menopause. They also showed no differences among normal, osteopenic and
      osteoporotic postmenopausal women. Serum levels of OPG were positively correlated
      with urinary excretion of NTx (r = 0.1453, P = 0.006). Serum levels of RANKL (r =
      -0.1928, P < 0.001) and RANKL/OPG ratio (r = -0.1303, P = 0.013) were inversely
      correlated with serum concentrations of OC. In multiple regression analysis, up
      to 20% variance (R(2) = 0.106-0.224) of the OPG-RANKL system in peripheral
      circulation can be explained by age, menopause and bone markers. These results
      suggest that although serum OPG and RANKL concentrations were unrelated with
      BMDs, the age- and menopause- dependent changes of serum OPG and RANKL might be a
      protective mechanism against the accelerated bone loss in postmenopausal women.

PMID- 15455184
TI  - Diffusion systems for evaluation of biomineralization.
AB  - A variety of in vitro study methods have been used to elucidate the roles of
      matrix molecules in biomineralization processes. Among these, gel diffusion
      precipitation studies have proved to be an effective tool. This methodology is
      uniquely capable of characterizing the effects of matrix molecules on
      mineralization while only using very small quantities of material. Furthermore,
      gel methods have been extended for use as a mineralization assay system to
      characterize modified matrix molecules and synthetic analogues. Here we discuss
      the advantages and limitations of gelatin, agar, agarose, and other systems for
      studying the mechanisms of biomineralization.

PMID- 15455185
TI  - Validation of thoracic quantitative computed tomography as a method to measure
      bone mineral density.
AB  - The purpose of this study was to measure precision of thoracic quantitative
      computed tomography (QCT) bone mineral density (BMD) and correlation to lumbar
      spine QCT bone density. We measured the reproducibility of thoracic QCT; two
      consecutive thoracic QCT scans of the T9, T10, and T11 vertebrae were performed
      on 95 subjects (49 females, 46 males; mean age, 62.5 years) undergoing coronary
      scanning. In order to correlate the thoracic to standard lumbar measurement, the
      subjects also underwent a lumbar QCT scan of the L1, L2, and L3 vertebrae as part
      of an abdominal aortic scanning study. The variation of thoracic BMD was assessed
      in different ethnic subgroups. Consecutive thoracic QCT measurements showed good
      agreement (r=0.98; RMS CV=5.78%). Thoracic bone density was significantly higher
      than lumbar bone density results (paired t-test, P=0.003), but the two methods
      correlated well (r=0.86). The regression equation for the relationship between
      lumbar (X) and thoracic (Y) QCT was Y=0.87X + 22.97. The standard error of
      estimate was 19.0 mg/cm3. Thoracic QCT from coronary calcium thoracic scans is
      able to measure BMD with rescan precision and regression errors that are small
      compared to the biologic variability in the population. Given the relatively
      small precision error and the reasonable correlation to lumbar BMD, an ancillary
      assessment of thoracic BMD in a cardiac scan is likely to be a useful assessment
      of bone mineral status in the general population.

PMID- 15455186
TI  - Dual energy X ray absorptiometry of ex vivo HcB/Dem mouse long bones: left are
      denser than right.
AB  - Dual energy X ray absorptiometry (DXA) has become a popular analytical technique
      in mice and other small animals. Comparative study of bone properties at
      different anatomical sites is an active area of study in model organisms. Such
      investigations require that site-specific data be generated and interpreted.
      There are no published data addressing the degree to which contralateral mouse
      bones resemble each other in the absence of an experimental intervention, nor are
      there data addressing the correlation of bone densitometry measurements between
      anatomically distant sites. To address these gaps in our knowledge, we used DXA
      to compare excised mouse femora and humeri. At the population level, left bones
      were slightly but significantly denser than right bones, with an overall adjusted
      bone mineral density (BMD) difference of 0.7 +/- 0.3 and 0.5 +/- 0.2 mg/cm2 at
      the femur and humerus, respectively. At the level of bone pairs from a single
      animal, absolute adjusted BMD disparities between the right and left sides were
      2.3 +/- 1.9 mg/cm2 at the femur and 1.7 +/- 1.4 mg/cm2 at the humerus.
      Correlation coefficients between left and right sides were 0.78 for adjusted BMD
      at both sites. The correlation coefficient between side-averaged femoral and
      humeral BMD was 0.81, but ranged between 0.70 and 0.75 when limited to
      ipsilateral or contralateral femur-humerus pairs. Our findings suggest the
      desirability of randomizing limbs for treatment in studies using contralateral
      limb controls. These observations may represent the densitometric manifestation
      of behavioral and neuroanatomical lateralization in laboratory mice.

PMID- 15455187
TI  - Paget's disease of bone in New Zealand: continued decline in disease severity.
AB  - We have reported previously that severe Paget's disease of bone had become less
      common at our center between 1973 and 1993. Data from several countries support
      the view that there are important secular trends in the prevalence and severity
      of Paget's disease. In this paper we describe recent trends in the demography of
      newly referred patients with Paget's disease to determine if the secular trend
      toward milder disease has continued. A database of all newly referred patients (n
      = 1487) with Paget's disease (1973 to 2002 inclusive, 30 years) was examined. Of
      these, 832 subjects (56%) had scintiscans. Plasma total alkaline phosphatase
      (total ALP) activity, disease extent on scintiscan, and a derived index of
      average ALP activity of pagetic bone were used as indices of severity. The number
      of new referrals with Paget's disease declined sharply from 1994 onward and is
      currently at half the rate seen 20 years earlier, while the mean age at
      presentation has progressively increased by 4 years per decade (P < 0.0001).
      Total ALP at diagnosis, disease extent on scintiscan, and the number of bones
      involved were all negatively correlated with both date of birth (P < 0.0001) and
      year of presentation (P < 0.0001), indicating that more recently born and
      presenting subjects had substantially less severe bone disease. The average
      activity of pagetic bone was only weakly correlated with year of presentation,
      but not with year of birth or age at presentation. Although there are a number of
      potential biases, these data are consistent with a continued secular trend to
      presentation in older subjects with less extensive skeletal involvement, and a
      declining prevalence of Paget's disease.

PMID- 15455188
TI  - Seven years of treatment with risedronate in women with postmenopausal
      osteoporosis.
AB  - The effects of 7 years of risedronate treatment were evaluated in a second 2-year
      extension of a 3-year vertebral fracture study in women with osteoporosis. For
      the first 5 years of the study, women received risedronate 5 mg/day or placebo
      according to the original randomization, with maintenance of blinding. All the
      women who entered into the 6-7 years extension study received risedronate 5
      mg/day. Endpoints included vertebral and nonvertebral fracture assessments,
      changes in biochemical markers of bone turnover, and bone mineral density (BMD)
      measurements. A total of 164 women (placebo/risedronate group, 81; risedronate
      group, 83) entered the 6-7 years extension study and 136 (83%) completed the
      study. Annualized incidence of new vertebral fractures during the 6-7 years was
      similar between the 2 treatment groups (3.8%). The incidence of vertebral
      fractures did not change in the 7-year risedronate group during the 6-7 years as
      compared to 4-5 years, while a significant reduction was observed in the placebo
      group that switched to risedronate treatment during years 6-7. The incidence of
      nonvertebral fractures was 7.4% and 6.0% in the placebo/risedronate and
      risedronate groups, respectively, during years 6-7. Urinary N-telopeptide
      decreased from baseline by 54% and 63% at 3 months and 7 years, respectively, in
      the risedronate group. The increases in BMD from baseline after 5 years of
      risedronate treatment were maintained or increased further during years 6-7;
      lumbar spine BMD after 5 and 7 years of risedronate treatment increased from
      baseline by 8.8% and 11.5%, respectively, for this extension study population.
      Risedronate was well tolerated and the occurrence of upper gastrointestinal
      adverse events was low. After 7 years of continuous risedronate treatment there
      were significant increases in BMD and decreases in bone turnover to within
      premenopausal levels and there was no indication of any loss of anti-fracture
      efficacy.

PMID- 15455189
TI  - N-Arylamine derivatives of 3-hydroxy-4-pyridinones: solution studies and
      bioevaluation in view of Al-detoxification roles.
AB  - A study of a series of bifunctional 3-hydroxy-4-pyridinone derivatives,
      containing side-chains with various alkyl-aryl-amine-amides as extra-functional
      groups, was conducted to assess the relevance of those groups to the Al-chelating
      affinity, the lipo-hydrophilic balance of the compounds, and 67Ga biodistribution
      in mice, in view of their potential use as Al-decorporating agents; the results
      were compared with those for the drug Deferriprone. Their acid-base properties
      and Al-chelating affinity in aqueous solution were studied by potentiometric
      techniques. These ligands form very stable tris-chelated Al complexes and the non
      chelating extra-groups are only responsible for small differences in the complex
      stability (DeltapAl< or =1.2). At physiological pH the major ligand/complex
      species have different charges, because of the different extent of protonation of
      the ligands. The introduction of the different groups induces a well-balanced
      stepwise-like lipo-hydrophilic character (-0.2 < log D(oct./water) < +1.1). The
      effect of each ligand on the biodistribution of 67Ga in overloaded mice is rapid
      blood clearance for all of them, but with different biodistribution patterns,
      namely excretion pathways and brain uptake/clearance, thus suggesting potential
      different clinical use.

PMID- 15455190
TI  - Novel separation method for highly sensitive speciation of cancerostatic platinum
      compounds by HPLC-ICP-MS.
AB  - A high-performance liquid chromatography-inductively coupled plasma mass
      spectrometry (HPLC-ICP-MS) method is presented for analysis of cisplatin,
      monoaquacisplatin, diaquacisplatin, carboplatin, and oxaliplatin in biological
      and environmental samples. Chromatographic separation was achieved on
      pentafluorophenylpropyl-functionalized silica gel. For cisplatin, carboplatin,
      and oxaliplatin limits of detection of 0.09, 0.10, and 0.15 microg L(-1),
      respectively, were calculated at m/z 194, using aqueous standard solutions. (3
      microL injection volume). The method was utilized for model experiments studying
      the stability of carboplatin and oxaliplatin at different chloride concentrations
      simulating wastewater and surface water conditions. It was found that a high
      fraction of carboplatin is stable in ultrapure water and in solutions containing
      1.5 mol L(-1) Cl-, whereas oxaliplatin degradation was increased by increasing
      the chloride concentration. In order to support the assessment of oxaliplatin eco
      toxicology, the method was tested for speciation of patient urine. The urine
      sample contained more than 17 different reaction products, which demonstrates the
      extensive biotransformation of the compound. In a second step of the study the
      method was successfully evaluated for monitoring cancerostatic platinum compounds
      in hospital waste water.

PMID- 15455191
TI  - Percutaneous penetration and metabolism of 2-butoxyethanol.
AB  - 2-Butoxyethanol (2-BE) is widely used as an industrial solvent, which may result
      in human dermal exposure within the workplace. This study compares in vivo and in
      vitro skin absorption of 2-BE using similar application regimes and determines
      the potential of skin to metabolise this chemical prior to entering the systemic
      blood circulation. Following topical application of undiluted [1-14C] 2-BE to
      occluded rat skin in vivo, 28% of the dose was absorbed after 24 h. The major
      routes of excretion included the urine (19%), expiration as carbon dioxide (6%)
      and faeces (0.4%) whilst little of the dose remained in the carcass (1.3%). Free
      2-BE (0.5%), butoxyacetic acid (8%), glucuronide conjugate (3%), sulphate
      conjugates (0.7%) and ethylene glycol (0.6%) were detected in urine. Permeation
      rates of 2-BE through unoccluded rat dermatomed skin (16%) were greater than rat
      whole skin (8%) whilst absorption through human dermatomed skin (4%) was lower
      than the rat. Absorption of undiluted 2-BE through occluded rat dermatomed skin
      in vitro (18%) most accurately predicted absorption through rat skin in vivo.
      However, 2-BE absorption (23%) was enhanced by application in methanol.
      Distribution analysis and microautoradiography demonstrated the lack of 2-BE
      accumulation within the skin in vitro or in vivo. This was reflected in the
      absence of first pass metabolism of 2-BE during percutaneous penetration through
      viable human or rat skin in vitro or rat skin in vivo, despite rat skin cytosol
      having the potential to metabolise 2-BE. In conclusion, the in vitro system
      provided a reasonable estimate of dermal absorption in vivo for the rat.
      Therefore, by extrapolation of the comparative in vitro data for human and rat
      skin in vitro, dermal absorption of 2-BE in man was about one-fifth of that in
      the rat. However, the rapid penetration through skin in vitro prevented local
      metabolism and systemic exposure after skin contact with 2-BE in vivo was likely
      to be to the parent compound. Thus, in vitro skin systems can be used to model
      dermal absorption of volatile glycol ethers, to predict how much compound enters
      the circulation and allows the toxicologist to evaluate the body burden of a
      chemical and potential systemic toxicity.

PMID- 15455192
TI  - Propanol as an end product of threonine fermentation.
AB  - Clostridium sp. strain 17cr1 was able to ferment L-threonine to propionate and
      propanol. Electrons arising in the oxidation of 2-oxobutyrate to propionyl-CoA
      were apparently used in reductive pathway leading to propanol formation. Part of
      the propionyl-CoA was used to form propionate in an ATP-forming pathway via a
      propionate kinase, so that the final ATP yield was 0.5 mol per mol of L-threonine
      metabolised. Other growth substrates were fermented mainly to acetate and
      butyrate, and the reductive formation of butyrate, from 2 mol of acetyl-CoA or
      from crotonate or 3-hydroxybutyrate, was the main route for recycling reduced
      electron carriers arising during oxidative pathways for most substrates.

PMID- 15455193
TI  - Longitudinal progression of fracture prevalence through a population of
      postmenopausal women with osteoporosis.
AB  - AIM: To determine the longitudinal progression of fractures through a population
      of osteoporotic women with no existing vertebral fractures. METHODS: The
      probability of having one or more vertebral fractures in the next year given a
      current status of 0-13 existing vertebral fractures was estimated using data from
      control patients of an osteoporosis clinical trial program. Fracture
      probabilities were used to form a transition matrix that models the change in
      fracture state from one year to the next. A Markov model was used to show the
      distribution of fracture prevalence over time for a population of women with
      osteoporosis but, initially, with no existing vertebral fractures. RESULTS: An
      osteoporotic woman without existing vertebral fractures has a 7.7% chance (95%
      CI, 5.8% to 9.9%) of having a vertebral fracture within 1 year. After 5 years,
      33% (95% CI, 25% to 41%) will have developed vertebral fractures, of which 11%
      (95% CI, 8% to 16%) will have > or =2 fractures. After 10 years, 55% (95% CI, 44%
      to 65%) will have developed vertebral fractures, of which 29% (95% CI, 22% 37%)
      will have > or =2 fractures. Each 1% absolute reduction in the annual first
      fracture risk corresponds to an approximate 4% reduction in the 5-year fracture
      incidence. Therefore, reducing the risk of first fracture from 8% to 2% reduces
      the 5-year fracture incidence from approximately 34% to approximately 10%.
      CONCLUSIONS: Fracture prevalence rapidly increases over time in a population of
      osteoporotic women despite treatment with calcium and vitamin D supplements.
      Identifying and treating patients at risk of fracture, but who have not yet
      sustained a fracture, will substantially reduce the long-term burden of
      osteoporosis.

PMID- 15455194
TI  - Alcohol intake as a risk factor for fracture.
AB  - High intakes of alcohol have adverse effects on skeletal health, but evidence for
      the effects of moderate consumption are less secure. The aim of this study was to
      quantify this risk on an international basis and explore the relationship of this
      risk with age, sex, and bone mineral density (BMD). We studied 5,939 men and
      11,032 women from three prospectively studied cohorts comprising CaMos, DOES, and
      the Rotterdam Study. Cohorts were followed for a total of 75,433 person-years.
      The effect of reported alcohol intake on the risk of any fracture, any
      osteoporotic fracture, and hip fracture alone was examined using a Poisson model
      for each sex from each cohort. Covariates examined included age and BMD. The
      results of the different studies were merged using weighted beta-coefficients.
      Alcohol intake was associated with a significant increase in osteoporotic and hip
      fracture risk, but the effect was nonlinear. No significant increase in risk was
      observed at intakes of 2 units or less daily. Above this threshold, alcohol
      intake was associated with an increased risk of any fracture (risk ratio [RR] =
      1.23; 95% CI, 1.06-1.43), any osteoporotic fracture (RR = 1.38; 95% CI, 1.16
      1.65), or hip fracture (RR = 1.68; 95% CI, 1.19-2.36). There was no significant
      interaction with age, BMD, or time since baseline assessment. Risk ratios were
      moderately but not significantly higher in men than in women, and there was no
      evidence for a different threshold for effect by gender. We conclude that
      reported intake of alcohol confers a risk of some importance beyond that
      explained by BMD. The validation of this risk factor on an international basis
      permits its use in case-finding strategies.

PMID- 15455195
TI  - Differences in hip quantitative computed tomography (QCT) measurements of bone
      mineral density and bone strength between glucocorticoid-treated and
      glucocorticoid-naive postmenopausal women.
AB  - Chronic treatment with glucocorticoids (GCs) leads to significant bone loss and
      increased risk of fractures. In chronically GC-treated patients, hip fracture
      risk is nearly 50%. The purpose of this investigation was to determine if there
      are differences in the quantities of trabecular and cortical bone and bone
      strength of the hip between GC-treated osteoporotic patients and controls.
      METHODS: Study subjects were GC-treated osteoporotic postmenopausal women, and
      controls were postmenopausal women, recruited for separate clinical trials.
      Quantitative computed tomography (QCT) and dual-energy X-ray absorptiometry (DXA)
      of the hip were obtained from all subjects. QCT outcome variables measured
      included total, cortical, and trabecular BMD of hip subregions (femoral neck and
      trochanter) and total hip. In addition, finite element modeling (FEM) was
      performed on a subset of 19 cases and 38 controls, matched on age (+/- 5 years),
      weight (+/- 5 kg), and history of hormone replacement (> 1 year use) to assess
      failure load in stance and fall loading conditions. Generalized linear models
      were used to adjust the QCT variables for covariates between groups. Multiple
      regression was performed to identify independent predictors of bone strength from
      the QCT variables. RESULTS: Compared with controls, GC-treated subjects were
      significantly (p < 0.05) younger, weighed less, and had more years of hormone
      replacement. QCT of the hip in GC-treated subjects for total femoral integral,
      cortical, and trabecular BMD averaged 4.9-23.2% (p < 0.002) less than controls,
      and similar results were seen by hip subregion including the trochanter and
      femoral neck. DXA of the total hip was 17% lower in GC subjects than controls (p
      < 0.05). Compared with controls, FEM failure load in GC subjects was 15% (p<0.05)
      and 16% (p = 0.07) lower for stance and fall loading conditions, respectively.
      Multiple regression analysis demonstrated that a combination of QCT measures was
      correlated with bone strength as measured by FEM. CONCLUSIONS: Chronic GC
      treatment in postmenopausal women resulted in significantly decreased BMD of the
      hip, measured by QCT, with loss of both trabecular and cortical bone. In
      addition, GC treatment decreased bone strength as determined by FEM. The reduced
      cortical and trabecular bone mass in the hip may contribute to the
      disproportionately high hip fracture rates observed in GC-treated subjects.

PMID- 15455196
TI  - Tubal ligation and the risk of vertebral fractures.
AB  - Osteoporosis is a major public problem. More than 35 million Americans are at
      risk of developing osteoporosis. Nearly half of all women will have an
      osteoporotic fracture in their lifetime. Tubal ligation (tubal sterilization) is
      used more than any other single method of contraception in the USA and worldwide.
      In 1995, 34.6% (approximately 7 million) of ever-married US women between ages 35
      44 years had undergone tubal ligation. Tubal sterilization may disturb ovarian
      function and be associated with more menstrual and menopausal symptoms and, thus,
      may be a risk factor for osteoporosis. The objective of this paper is to examine
      the possible association between tubal sterilization and osteoporotic fractures.
      Data are from a questionnaire mailed to a previously identified cohort of
      college/university alumnae who had graduated between 1926 and 1981. This study
      was performed during 1996 and 1997, 15 years after the initial study. The
      subjects were 3,940 women participants in the follow-up study. Their mean age was
      53.7 years at time of reporting, ranging from 37 to over 80 years. Excluding
      deaths and non-deliverables the response rate was 85%. Of the 3,940 subjects, 491
      (12.5%), and, of the ever-pregnant women, 15.5%, had undergone tubal
      sterilization (TS); 899 (22.8%) reported at least one fracture after age 20, and
      70 (1.8%) at least one vertebral fracture after age 20, which had been confirmed
      by X-ray. TS was strongly associated with self-reports of vertebral fractures
      that had been confirmed by X-ray. The multivariable adjusted odds ratios and 95%
      confidence intervals for women 50 years and over and for women 55 years and over
      were, respectively, 2.7 (1.4, 5.0) and 3.3 (1.5, 7.0). Having had any fracture
      was not significantly associated with TS: odds ratio (OR) = 1.1 for women 50
      years and older and OR = 1.3 for those 55 years and older. This epidemiological
      study in a cohort of highly educated, mostly Caucasian women shows an association
      between past tubal sterilization and self-reported X-ray-confirmed vertebral
      fractures. These results need to be confirmed in other cohorts--the
      pathophysiology of this association is worthy of further study.

PMID- 15455198
TI  - Arthroscopic meniscal repair with an absorbable screw: results and surgical
      technique.
AB  - The results of a new method for arthroscopic all-inside meniscus repair using a
      biodegradable cannulated screw (Clearfix meniscal screw) were assessed in a
      medium-term follow-up prospective study. The Clearfix meniscal screw system
      consists of delivery cannulae, screw driver, and screw implants. After tear
      debridement, a screw is located on the driver and passed through the cannula to
      the insertion site, holding the two sides of the tear together under linear
      compression. Forty-eight patients (48 repairs) with a mean age of 32.7 years were
      included in the study. Ligament stabilizing procedures were done in 39 patients
      (81%) who had anterior cruciate ligament deficient knees. Only longitudinal
      lesions in the red/red or red/white zone were repaired. Follow-up averaged 19
      months, with a range from 12 to 48 months. Patients were evaluated using clinical
      examination, the "Orthopaedische Arbeitsgemeinschaft Knie (OAK)" knee evaluation
      scheme and magnetic resonance imaging (MRI). Criteria for clinical success
      included absence of joint-line tenderness, absence of swelling and a negative
      McMurray test. Postoperatively, there were no complications directly associated
      with the device. Twelve of 48 repaired menisci (25%) were considered failures
      according to the above-mentioned criteria. According to the OAK knee evaluation
      scheme, 38 patients (79%) had an excellent or good result. MRI, however, showed
      persisting grade III or IV lesions in 35 patients (73%). Analysis showed that
      age, length of tear, and simultaneous anterior cruciate ligament reconstruction
      did not affect the clinical outcome. In contrast, risk factors for failure of
      meniscus repair are chronicity of injury, location of tear more than 3 mm from
      the meniscosynovial junction and meniscus side (medial).

PMID- 15455197
TI  - Bone density and hemoglobin levels in older persons: results from the InCHIANTI
      study.
AB  - Hypoxemia has been recognized as a risk factor for bone loss. The aim of the
      present study is to investigate the relationship of bone mass and density
      measures with anemia and hemoglobin levels in a large sample of older community
      dwelling persons. The study is based on data from 950 participants enrolled in
      the "Invecchiare in Chianti" (Aging in the Chianti area, InCHIANTI) study. All
      the analyses were performed considering continuous hemoglobin levels as well as
      the dichotomous anemia variable (defined according to WHO criteria as hemoglobin
      < 12 g/dl in women and < 13 g/dl in men). A peripheral quantitative computerized
      tomography (pQCT) scan of the right calf was performed in all participants to
      evaluate total bone density, trabecular bone density, cortical bone density, and
      the ratio between cortical and total bone area. Linear regression analyses were
      used to assess the multivariate relationship of pQCT bone measures with anemia
      and hemoglobin levels after adjustment for demographics, chronic conditions,
      muscle strength and biological variables. Participants were 75.0 (SD 6.9) years
      old. In our sample, 101 participants (10.6%) were anemic. In women, coefficients
      from adjusted linear regression analyses evaluating the association between pQCT
      bone measures (per SD increase) and hemoglobin levels/anemia showed significant
      associations of anemia with total bone density (beta = -0.335, SE = 0.163; P =
      0.04) and cortical bone density (beta = -0.428, SE = 0.160; P = 0.008).
      Relationships with borderline significance were found for the associations of
      anemia with trabecular bone density and the ratio between cortical and total bone
      area. Significant associations were found between hemoglobin levels and
      trabecular bone density (beta = 0.112, SE = 0.049; P = 0.02), total bone density
      (beta = 0.101, SE = 0.046; P = 0.03), cortical bone density (beta = 0.100, SE =
      0.046; P = 0.03) and the ratio between cortical bone and total area (beta =
      0.092, SE = 0.045; P = 0.04). In men, significant associations were found for
      hemoglobin levels with total bone density (beta = 0.076, SE = 0.036; P = 0.03)
      and cortical bone density (beta = 0.095, SE = 0.41; P = 0.02). A borderline
      significance was reported for the association between anemia and cortical bone
      density. We concluded that anemia and low hemoglobin levels are negatively and
      independently associated with bone mass and density. The bone loss associated
      with hemoglobin levels mainly occurs in the cortical bone. Women with lower
      hemoglobin levels demonstrate a higher bone loss than male counterparts.

PMID- 15455199
TI  - [Umbilical cord stromal cells (UCSC). Cells featuring osteogenic differentiation
      potential].
AB  - The identification of appropriate cell types is necessary to establish cell-based
      therapies in regenerative medicine. These cell types must (1) be available in an
      appropriate amount, (2) be easy to obtain, (3) be sufficiently expandable in
      vitro, and (4) fit to or at least be able to differentiate into the required cell
      type. Since the umbilical cord is available without any intervention and
      represents a notable amount of tissue, we consider it to be a promising source
      for isolating cells for cell-based therapies. This study demonstrates that
      umbilical cord stromal cells (UCSC), the connective tissue cells of the umbilical
      cord, can be isolated in sufficient quantities and be well expanded. UCSC feature
      phenotypic plasticity and thus are functionally similar to stem cells. UCSC can
      be differentiated into cells with osteoblastic properties (expression of alkaline
      phosphatase, formation of bone nodules). It is concluded that the umbilical cord
      should no longer be regarded as valueless tissue and be unthinkingly discarded.
      Instead, it should be considered a valuable resource for the isolation of potent
      cells for cell-based therapies, especially for treatment of bone defects.

PMID- 15455200
TI  - In the lipodystrophy associated with highly active antiretroviral therapy, pseudo
      Cushing's syndrome is associated with increased regeneration of cortisol by
      11beta-hydroxysteroid dehydrogenase type 1 in adipose tissue.
AB  - AIMS/HYPOTHESIS: Highly active antiretroviral therapy (HAART) in patients
      infected with human immunodeficiency virus (HIV) is associated with a poorly
      understood lipodystrophic and hypertriglyceridaemic syndrome, which resembles
      Cushing's syndrome, but in which plasma cortisol is not elevated. We tested the
      hypothesis that this HAART-associated lipodystrophy is explained by increased
      local regeneration of cortisol from inactive cortisone within adipose tissue,
      catalysed by the enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1).
      METHODS: In this cross-sectional study, a previously described cohort of 30 HIV
      infected patients with lipodystrophy were compared with 13 HIV-infected patients
      without lipodystrophy. Intra-abdominal and subcutaneous adipose tissue were
      quantified using magnetic resonance imaging. Gene expression in subcutaneous fat
      was measured using real-time PCR. Urine cortisol and its metabolites were
      analysed by gas chromatography/mass spectrometry. RESULTS: Patients with
      lipodystrophy had significantly higher 11beta-HSD1 mRNA concentrations (relative
      to beta2-microglobulin mRNA) in subcutaneous adipose tissue than non
      lipodystrophic patients (0.29+/-0.20 vs 0.09+/-0.07, p=0.0004) and higher ratios
      of urinary cortisol : cortisone metabolites. Adipose tissue 11beta-HSD1 mRNA
      correlated with multiple features of insulin resistance and with mRNA
      concentrations for glucocorticoid receptor and angiotensinogen.
      CONCLUSIONS/INTERPRETATION: In adipose tissue of patients with HAART-associated
      lipodystrophy, 11beta-HSD1 mRNA is increased and its concentration is correlated
      with features of insulin resistance. We suggest that increased adipose tissue
      11beta-HSD1 may explain the pseudo-Cushing's features in patients with HAART
      associated lipodystrophy, and is a potential therapeutic target.

PMID- 15455201
TI  - [Indications for the urodynamic diagnosis in adults].

PMID- 15455202
TI  - [Spondylodiscitis caused by septicemia after transrectal prostate biopsy. An
      extremely rare complication--case report].
AB  - Spondylodiscitis after prostate biopsy is a very rare complication. Only two
      cases have been published in the literature.A transrectal prostate biopsy was
      performed in a 59-year-old man. Postoperatively a septic condition with fever and
      back pain developed. The correct diagnosis was delayed because of "acute abdomen"
      and pneumonia. The spondylodiscitis with abscess formation in thoracic vertebral
      bodies was only found later and adequate and successful surgical treatment was
      performed.

PMID- 15455203
TI  - [Tissue engineering of the urethra and ureter].
AB  - Congenital or acquired disorders of the urethra or ureter often require adequate
      tissue transfer for reconstruction. A variety of biomaterials have proved to be
      useful in the reconstruction of the urethra or ureter in animal models and
      meanwhile even clinically. Innovative tissues such as acellular matrices can be
      placed in the host and function as a scaffold to allow the natural process of
      tissue regeneration. Biodegradable scaffolds can also be used as cell
      transplantation vehicles for the reconstruction of urethral or ureteral tissue.
      One of the limitations of cell-based tissue engineering techniques however is the
      difficulty of growing genitourinary-associated cells in large quantities in
      primary cultures. It can be speculated that stem cell research might help to
      overcome this specific problem in the future.

PMID- 15455204
TI  - [Embryonic and adult stem cells for tissue engineering in urology].
AB  - Stem cells are considered a possible alternative treatment for degenerative
      diseases. Parkinson's disease and diabetes mellitus may become curable using stem
      cells. The term "stem cell" is used very broadly, although it has been well
      defined. Undifferentiated cells (stem cells and progenitor cells) are isolated
      from prenatal and postnatal tissues. This review provides an overview of
      embryonic and adult stem cells and describes potential applications in the field
      of tissue engineering in urology.

PMID- 15455205
TI  - [Proximal protection systems using carotid artery stent].
AB  - Controversies as to whether or not a protection device should be used in carotid
      artery stenting exist. Currently three temporary cerebral protection devices are
      being used. These are devices with distal balloon occlusion or filtration baskets
      and proximal occlusion devices with flow reversal in the internal carotid artery.
      This article focuses on flow reversal systems and aims to give some advice as to
      which patients could benefit from their use.

PMID- 15455206
TI  - [Treatment of arteriosclerotic carotid stenosis: an overview].
AB  - Endarterectomy for extracranial carotid stenosis has proven to be the method of
      choice for symptomatic patients suffering from ischemia (NASCET, ECST). The
      effectivity of the operation for asymptomatic stenosis seems to be likely since
      the publication of the first results of the ACST trial. The safety and efficiency
      of carotid stenting has not been proven so far and has to be evaluated in
      randomized trials comparing surgery and endovascular treatment. We provide an
      overview of the current trials and try to define the role of carotid stenting.

PMID- 15455207
TI  - Scale-dependent habitat selection in migratory frugivorous passerines.
AB  - Frugivorous migrants may select fruit-rich habitats en route to attain high food
      rewards, yet their stopover behavior may also be shaped by other considerations,
      such as predation risk. During 1996-2001 we investigated autumn stopover habitat
      use of three Sylvia warblers (sylviids; S. hortensis, S. atricapilla and S.
      curruca) and three Turdidae chats (turdids; Cercotrichas galactotes, Oenanthe
      hispanica and Phoenicurus phoenicurus) in planted groves of the fruiting tree
      Pistacia atlantica in Lahav Forest, Israel, which is located at the edge of a
      desert. We used fecal analysis, a constant-effort trapping scheme and field
      observations to estimate the extent of frugivory, and bird habitat and
      microhabitat selection with regard to natural fruit and foliage densities. We
      also measured bird microhabitat selection in a set of fruit-manipulated trees. We
      trapped a total of 2,357 birds during the course of the study. Although sylviids
      exhibited higher frugivory level than turdids, both species groups exhibited a
      similar significantly positive correlation between bird and fruit densities at
      the habitat scale. However, at the microhabitat scale, sylviids selected densely
      foliated trees, whilst turdids were randomly distributed among trees. Our
      findings suggest that both species groups selected fruit-rich stopover habitats
      to take advantage of the high food availability before the demanding migration
      journey. No other mechanism except predation avoidance can explain the sylviids'
      microhabitat selection; the migrants used foliage cover to reduce bird
      detectability by raptors. We conclude that en route passerines may use staging
      habitats in a sophisticated manner, by adopting scale-related behavior with
      regard to the availability of food and refuge cover.

PMID- 15455210
TI  - Trehalose biosynthesis in Thermus thermophilus RQ-1: biochemical properties of
      the trehalose-6-phosphate synthase and trehalose-6-phosphate phosphatase.
AB  - The genes for trehalose synthesis in Thermus thermophilus RQ-1, namely otsA
      [trehalose-phosphate synthase (TPS)], otsB [trehalose-phosphate phosphatase
      (TPP)], and treS [trehalose synthase (maltose converting) (TreS)] genes are
      structurally linked. The TPS/TPP pathway plays a role in osmoadaptation, since
      mutants unable to synthesize trehalose via this pathway were less osmotolerant,
      in trehalose-deprived medium, than the wild-type strain. The otsA and otsB genes
      have now been individually cloned and overexpressed in Escherichia coli and the
      corresponding recombinant enzymes purified. The apparent molecular masses of TPS
      and TPP were 52 and 26 kDa, respectively. The recombinant TPS utilized UDP
      glucose, TDP-glucose, ADP-glucose, or GDP-glucose, in this order as glucosyl
      donors, and glucose-6-phosphate as the glucosyl acceptor to produce trehalose-6
      phosphate (T6P). The recombinant TPP catalyzed the dephosphorylation of T6P to
      trehalose. This enzyme also dephosphorylated G6P, and this activity was enhanced
      by NDP-glucose. TPS had an optimal activity at about 98 degrees C and pH near
      6.0; TPP had a maximal activity near 70 degrees C and at pH 7.0. The enzymes were
      extremely thermostable: at 100 degrees C, TPS had a half-life of 31 min, and TPP
      had a half-life of 40 min. The enzymes did not require the presence of divalent
      cations for activity; however, the presence of Co2+ and Mg2+ stimulates both TPS
      and TPP. This is the first report of the characterization of TPS and TPP from a
      thermophilic organism.

PMID- 15455211
TI  - Expression of proteasomal proteins in ten different tumor cell lines.
AB  - Controlled intracellular protein degradation is crucial for the maintenance of
      normal cell functions. An evolving concept claims that alterations in the exact
      timely degradation of proteins involved in growth control, apoptosis, signaling
      and differentiation contribute to carcinogenesis. This tightly regulated process
      is facilitated by the ubiquitin-26S proteasome system, a multi-enzyme complex,
      and inhibitors of this pathway have already been developed as potential
      anticancer agents. In order to generate proteasomal protein expression patterns
      of tumor cells and to provide an analytical tool we applied two-dimensional
      electrophoresis (2-DE) followed by mass spectrometry (MALDI-TOF-TOF with LIFT
      technology) in ten individual tumor cell lines (Saos-2; SK-N-SH; HCT-116; Caov3;
      A-549; HL60; A-673; A-375; MCF-7; HeLa) widely used in tumor research. A series
      of 39 proteasomal/proteolytic proteins was unambiguously identified by this
      proteomic approach, comprising proteins of the 20S core complex, the 19S
      regulatory complex, the 11S regulator, components of the ubiquitin pathway and
      proteases. Construction of individual protein maps by 2-DE and mass spectrometry
      provides an analytical tool and reference base for studying the pivotal
      importance of the proteasome and other proteolytic enzymes in tumor cells,
      independent of antibody availability and specificity. This preliminary database
      enables for designing studies in this area of research and reveals proteins that
      can be used as targets for new therapeutic strategies.

PMID- 15455212
TI  - Proteomic basis for the possible use of lymphocytes for metabolic screenings.
AB  - The advent of proteomics has provided a tool for the concomitant identification
      and determination of a large series of proteins using two-dimensional gel
      electrophoresis with subsequent mass spectrometrical analysis. We tried an
      approach to analyse the high abundance enzyme proteome of a lymphocytic cell
      line. Immortalised lymphocytes were grown in RPMI 1640 in the presence of
      glutamine, harvested and the 100,000 x g supernatant of the homogenate was
      applied on two-dimensional gel electrophoresis with subsequent in-gel digestion
      of protein spots and MALDI-TOF (Matrix-associated laser desorption/ionization
      mass spectroscopy) analysis of resulting peptides using specific software. A
      series of 57 metabolic enzymes were identified including enzymes of carbohydrate,
      amino acid, purine and intermediary metabolism. We are presenting a tool for the
      analysis of metabolic systems including enzyme deficiencies at the protein level
      with the advantage of unambiguous identification of proteins and thus
      complementing enzyme activity determinations.

PMID- 15455213
TI  - Proteomic identification of collagens and related proteins in human fibroblasts.
AB  - Fibroblasts are used for diagnosis of a series of metabolic diseases and are
      particularly suitable for the diagnosis of collagen disorders. We aimed to
      generate a skin fibroblast map that would be suitable for the concomitant
      determination of collagen and collagen-related proteins.A human skin fibroblast
      cell line was cultivated, homogenised, proteins extracted and subject to two
      dimensional gel electrophoresis with subsequent in-gel-digestion of protein spots
      and mass spectrometrical identification (MALDI-TOF). Collagen alpha1 (I) chain
      precursor, collagen alpha1 (III) chain precursor, collagen alpha2 (VI) precursor
      and collagen modifying enzymes prolyl 4-hydroxylase alpha-2-subunit precursor,
      procollagen-lysine 2-oxoglutarate 5-dioxygenase 1 and 2, protein disulfide
      isomerase ER-60 precursor and peptidyl-prolyl cis-trans isomerase were among the
      abundant proteins. The finding of collagen and collagen-related structures as
      well as the identification of other metabolic enzyme systems on one 2D gel may
      propose the use of this proteomic method for further characterization of collagen
      and collagen-related proteins or for preliminary screening of metabolic
      disorders.

PMID- 15455214
TI  - Gene expression profiling of parkinsonian substantia nigra pars compacta;
      alterations in ubiquitin-proteasome, heat shock protein, iron and oxidative
      stress regulated proteins, cell adhesion/cellular matrix and vesicle trafficking
      genes.
AB  - Gene expression profiling of human substantia nigra pars compacta (SNpc) from
      Parkinson's disease (PD) patients, was examined employing high density
      microarrays. We identified alterations in the expression of 137 genes, with 68
      down regulated and 69 up regulated. The down regulated genes belong to signal
      transduction, protein degradation (e.g. ubiquitin-proteasome subunits),
      dopaminergic transmission/metabolism, ion transport, protein
      modification/phosphorylation and energy pathways/glycolysis functional classes.
      Up-regulated genes, clustered mainly in biological processes involving cell
      adhesion/cytoskeleton, extracellular matrix components, cell cycle, protein
      modification/phosphorylation, protein metabolism, transcription and
      inflammation/stress (e.g. key iron and oxygen sensor EGLN1). One major finding in
      the present study is the particular decreased expression of SKP1A, a member of
      the SCF (E3) ligase complex specifically in the substantia nigra (SN) of sporadic
      parkinsonian patients, which may lead to a wide impairment in the function of an
      entire repertoire of proteins subjected to regulatory ubiquitination. These
      findings reveal novel players in the neurodegenerative scenario and provide
      potential targets for the development of novel drug compounds.

PMID- 15455215
TI  - Depressed skull fracture and epidural haematoma: an unusual post-operative
      complication of pin headrest in an adult.
AB  - Depressed skull fracture and epidural haematoma caused by pin headrest
      complicated the post-operative course in an adult, after removal of a
      parasagittal meningioma. The calvarial thickness was observed to be significantly
      reduced due to chronic high intracranial pressure. Potentially hazardous
      complications of pin headrests should not be underestimated in adults.

PMID- 15455216
TI  - Missile severances of the radial nerve. Results of 131 repairs.
AB  - BACKGROUND: Reports on missile-caused radial nerve injuries are relatively rare
      in current literature. We present the outcome after repair of such injuries as
      well as the factors influencing the result of treatment. METHODS: Prospective
      study included 131 complete missile-caused radial nerve severances repaired with
      nerve graft or direct suture. Final outcome was defined 4 years postoperatively
      at least, on the basis of motor recovery (M), EMNG recovery (E) and patient's
      judgement on the quality of outcome (P). Recovery was estimated with 0-5 points
      and final outcome was defined according to the total sum (0-15 points) as: poor,
      insufficient, good or excellent. Both the good and the excellent outcomes were
      considered as successful, and both the poor and the insufficient outcome as
      unsuccessful. RESULTS: Excellent outcome was noted in 38.2% and good outcome in
      47.3% of all patients. Average point score was 9.9 +/- 3.3 points for the whole
      series (domain of good outcome) and 6.6 +/- 3.0, 10.1 +/- 3.2 and 10.9 +/- 2.2
      points for high, intermediate and low repairs, respectively (p<0.01). Useful
      motor recovery (>or =M3), good EMNG recovery (> or =E3) and affirmative patient's
      judgement on the outcome (> or =P3) had similar frequencies for intermediate
      (83.2-89.7%) and low repairs (85.7-92.8%), but for high repairs, good EMNG
      recovery was more frequent (70%) than were useful motor recovery and affirmative
      patient's judgement (40%). Successful outcome was noted in 89.3% of direct
      sutures and in 82.7% of nerve grafts (p>0.05). Patients with a successful outcome
      had a significantly shorter nerve defect (p<0.001), shorter preoperative interval
      (p<0.001) and younger age (p<0.05) than patients with an unsuccessful outcome.
      Significant deterioration of results began with defects longer than 8 cm,
      preoperative interval longer than 6 months and age above 40 years. CONCLUSIONS:
      The outcome is significantly worse after high radial nerve repairs than after
      intermediate and low repairs. The length of nerve defect, duration of
      preoperative interval and age of the patient also influence the repair outcome.
      Correlation of motor recovery with EMNG recovery and with patient's judgement on
      the outcome is relatively good, but depends on the level of the repair.

PMID- 15455217
TI  - Pleomorphic xanthoastrocytoma of the cerebellum: illustrated review.
AB  - Although rarely, the usually benign, supratentorial, grade II astrocytic tumour
      pleomorphic xanthoastrocytoma (PXA) may arise from the cerebellum. A review of
      the published cases of these PXAs is made including the author's own case of a 40
      years-old man with a right cerebellopontine angle tumour, which recurred after a
      gross total resection. The major clinical and histopathological features of
      cerebellar PXAs are discussed, and factors playing a role in their biological
      behaviour, like post-surgical medical treatment, genetics and extent of
      leptomeningeal seeding are stressed.

PMID- 15455218
TI  - Multiple cerebral amoebic abscesses in a child.

PMID- 15455219
TI  - Lumboperitoneal shunts: are the complications acceptable?
AB  - BACKGROUND: Lumboperitoneal shunts have long been used in the treatment of benign
      intracranial hypertension, postoperative pseudomeningocele, CSF leak and
      communicating hydrocephalus. Although they can provide a rapid and effective
      resolution of the symptoms there are major disadvantages associated with their
      use. METHOD: We retrospectively analyzed the records of 21 patients who underwent
      LP shunt insertion in our institution during the study period. FINDINGS: Eighteen
      patients (85.7%) underwent at least one shunt revision with a total of 63
      revisions. Shunt related infections were observed in 7 cases and 7 patients
      developed Chiari malformation, 2 (9%) of these requiring further treatment.
      CONCLUSIONS: Despite the symptomatic control achieved with lumboperitoneal shunts
      we find the complication and revision rates unacceptably high. The technique
      should be re-evaluated and other treatment strategies considered.

PMID- 15455220
TI  - Postural intermittent headaches as the initial symptom of a cavernoma in the
      third ventricle.
AB  - Cavernous malformations (CM) occur very rarely in the ventricular system. We
      report a patient with a rare location in the third ventricle who had intermittent
      headaches as the initial symptom.

PMID- 15455221
TI  - Biomass change in an Atlantic tropical moist forest: the ENSO effect in permanent
      sample plots over a 22-year period.
AB  - There are a number of controversies surrounding both biomass estimation and
      carbon balance in tropical forests. Here we use long-term (from 1978 through
      2000) data from five 0.5-ha permanent sample plots (PSPs) within a large tract of
      relatively undisturbed Atlantic moist forest in southeastern Brazil to quantify
      the biomass increment (DeltaM(I)), and change in total stand biomass
      (DeltaM(stand)), from mortality, recruitment, and growth data for trees >/=10 cm
      diameter at breast height (DBH). Despite receiving an average of only 1,200 mm
      annual precipitation, total forests biomass (334.5+/-11.3 Mg ha(-1)) was
      comparable to moist tropical forests with much greater precipitation. Over this
      relatively long-term study, forest biomass experienced rapid declines associated
      with El Nino events, followed by gradual biomass accumulation. Over short time
      intervals that overlook extreme events, these dynamics can be misinterpreted as
      net biomass accumulation. However for the 22 years of this study, there was a
      small reduction in forest biomass, averaging -1.2 Mg ha(-1) year(-1) (+/-3.1).
      Strong climatic disturbances can severely reduce forest biomass, and if the
      frequency and intensity of these events increases beyond historical averages,
      these changing disturbance regimes have the capacity to significantly reduce
      forest biomass, resulting in a net source of carbon to the atmosphere.

PMID- 15455225
TI  - A newborn infant of a diabetic mother with refractory hypocalcaemic convulsions.

PMID- 15455226
TI  - Highly restricted pattern of connexin36 expression in chick somite development.
AB  - The gap junction protein connexin36 (CX36) has been well studied in the mature
      central nervous system, but there has been little information regarding its
      possible roles in embryonic development. We report here the isolation of the full
      length chick CX36 coding sequence (predicted M(r) 35.1 kDa) and its strikingly
      restricted pattern of gene expression in the mesoderm of the chick embryo. In
      situ hybridization experiments demonstrated CX36 expression in somites by
      embryonic day 2. The transcripts first appeared dorsomedially within the somite
      and expanded ventrolaterally to form stripes in the middle of each somite. The
      CX36 stripes fell within somitic territories enriched in MYOD and FGF8 expression
      and impoverished in PAX3 transcripts, establishing that CX36 mRNA is expressed in
      the myotome. We compared the somitic expression pattern of CX36 with those of
      three other connexins, CX42, CX43, and CX45. At embryonic day 4, CX42 transcripts
      were localized to the myotome in a pattern resembling that of CX36. In contrast,
      CX43 was enriched in the dermomyotome, and CX45 was detected in both the myotome
      and the dermomyotome. Immunoblotting using Cx36 antibodies demonstrated bands of
      identical electrophoretic mobilities in trunk and retinal homogenates, and Cx36
      immunostaining detected punctate immunoreactivity in the myotome. These results
      demonstrate that some connexins in the developing mesoderm are broadly expressed
      whereas others are highly localized, and suggest that CX36, CX42, and CX45 are
      involved in intercellular communication among developing muscle cells.

PMID- 15455227
TI  - The utility of immunohistochemical detection of DNA mismatch repair gene
      proteins.
AB  - Since the development of monoclonal antibodies against the MSH2 protein by Leach
      et al. in 1996, a series of investigations has been undertaken to determine the
      utility of immunohistochemical detection of DNA mismatch repair (MMR) gene
      proteins in the identification of hereditary or sporadic colorectal tumors with
      microsatellite instability. These studies, however, have been performed with
      different aims and on different patient populations. Interpretation of these
      immunohistochemical data relies on a thorough understanding of the biological and
      technical factors that affect the detection of MMR proteins. In this review, we
      analyze the data from the published research studies, pointing out the various
      factors affecting immunohistochemical detection of MMR proteins and projecting
      the utility of immunohistochemistry in different clinical settings.

PMID- 15455228
TI  - Malignant transformation of sialadenoma papilliferum of the palate: a case
      report.
AB  - We report a case of a 79-year-old woman with an unusual salivary gland tumor that
      developed at the junction between the soft and hard palates. The tumor consisted
      of sialadenoma papilliferum (SP) with areas of an epithelial-myoepithelial
      carcinoma (EMC) component and a high-grade carcinoma component. There were also
      transitional regions among the SP, the EMC and the high-grade carcinoma
      components. The high-grade carcinoma component, which was similar to invasive
      micropapillary carcinoma of the breast, infiltrated into the right parapharyngeal
      space and metastasized to the lungs and cervical vertebrae. The high-grade
      carcinoma cells were positively immunostained for p53 protein. SP has been
      considered to be a benign tumor with exceptionally good prognosis, and, to the
      best of our knowledge, there has never been a confirmed case of malignant SP.
      This is the first report of SP with a definite malignant component.

PMID- 15455229
TI  - Paraovarian hemangioma with immunoglobulin deposits in a patient with monoclonal
      gammopathy of uncertain significance and osteolytic lesions.

PMID- 15455230
TI  - c-KIT codon 816 mutation in a recurrent and metastatic dysgerminoma of a 14-year
      old girl: case study.
AB  - Dysgerminomas are rare female germ-cell tumors that correspond histologically and
      immunohistochemically to seminomas. Analogous to seminomas, most dysgerminomas
      respond very well to cisplatin- or carboplatin-based chemotherapy and to
      radiotherapy. KIT tyrosine kinase is crucial for normal germ-cell development,
      and its expression is observed in the majority of seminomas and dysgerminomas.
      Recently, activating KIT mutations were described in a panel of male germ-cell
      tumors [5, 10]. All mutations were localized in exon 17, encoding the second
      tyrosine kinase domain. Because receptor tyrosine kinase KIT might also be
      involved in the pathogenesis of dysgerminomas, we studied the expression and
      mutational status of a pure dysgerminoma, which was sent to our department for
      diagnostic reasons. The tumor revealed an exon 17 D816 V mutation in the c-KIT
      gene and strong KIT expression was found immunohistochemically. Clinically, the
      tumor was highly aggressive and resistant to carboplatin-based chemotherapy. Our
      case raises the question of whether exon 17 c-KIT mutations might be involved in
      the pathogenesis of dysgerminoma and whether exon 17 KIT mutations may predict
      aggressive and chemotherapy-resistant behavior of dysgerminomas.

PMID- 15455231
TI  - Factors of transforming growth factor beta signalling are co-regulated in human
      hepatocellular carcinoma.
AB  - Transforming growth factor beta (TGFbeta) is a central mitoinhibitory factor for
      epithelial cells, and alterations of TGFbeta signalling have been demonstrated in
      many different human cancers. We have analysed human hepatocellular carcinomas
      (HCCs) for potential pro-tumourigenic alterations in regard to expression of
      Smad4 and mutations and expression changes of the pro-oncogenic transcriptional
      co-repressors Ski and SnoN, as well as mRNA levels of matrix metalloproteinase-2
      (MMP2), which is transcriptionally regulated by TGFbeta. Smad4 mRNA was detected
      in all HCCs; while, using immunohistology, loss of Smad4 expression was found in
      10% of HCCs. Neither mutations in the transformation-relevant sequences nor
      significant pro-tumourigenic expression changes of the Ski and SnoN genes were
      detected. In HCC cell lines, expression of both genes was regulated, potentially
      involving phosphorylation. Ski showed a distinct nuclear speckled pattern,
      indicating recruitment to active transcription complexes. MMP2 mRNA levels were
      increased in 19% of HCCs, whereas MMP2 mRNA was not detectable in HCC cell lines,
      suggesting that MMP2 was derived only from tumour stroma cells. Transcript levels
      of Smad4, Ski, SnoN and MMP2 correlated well. These data argue against a
      significant role of Ski and SnoN in human hepatocarcinogenesis and suggest that,
      in the majority of HCCs, the analysed factors are co-regulated by an upstream
      mechanism, potentially by TGFbeta itself.

PMID- 15455232
TI  - Oncocytic carcinoma arising in Warthin tumour.

PMID- 15455233
TI  - Modulation of Na(v)1.5 by beta1-- and beta3-subunit co-expression in mammalian
      cells.
AB  - Cardiac sodium channels (Na(v)1.5) comprise a pore-forming alpha-subunit and
      auxiliary beta-subunits that modulate channel function. In the heart, beta1 is
      expressed throughout the atria and ventricles, whilst beta3 is present only in
      the ventricles and Purkinje fibers. In view of this expression pattern, we
      determined the effects of beta3 and beta1 co-expression alone, and in
      combination, on Na(v)1.5 stably expressed in Chinese hamster ovary cells. The
      current/voltage relationship was shifted -5 mV with either beta1 or beta3 co
      expression alone and -10 mV with co-expression of both beta1 and beta3. In
      addition, beta3 and beta1/beta3 co-expression accelerated macroscopic current
      decay. There were significant hyperpolarizing shifts in equilibrium gating
      relationships with co-expression of beta1 and beta3 alone and in combination. Co
      expression of beta1/beta3 together resulted in a greater hyperpolarizing shift in
      channel availability, and an increase in the slopes of equilibrium gating
      relationships. Co-expression of beta3 and beta1/beta3, but not beta1, slowed
      recovery from inactivation at -90 mV. Development of inactivation at -70 and -50
      mV was accelerated by beta-subunit co-expression alone and in combination. beta
      Subunit co-expression also reduced the late Na current measured at 200 ms. In
      conclusion, beta-subunits modulate Na(v)1.5 gating with important differences
      between co-expression of beta1 and beta3 alone and beta1/beta3 together.

PMID- 15455234
TI  - Colon cancer: survival after curative surgery.
AB  - Several new aspects have evolved during the past years concerning factors that
      influence survival in surgically and medically treated colon cancer patients that
      are relevant to the treating team for the treatment strategy and patient's
      choice. The 5-year-survival rates dependent on UICC stages/substages (I: 68%
      100%, II: 58%-90%, III: 33%-76%, IV: <5%-9%) show remarkable variations between
      published reports, surgical hospital units, individual surgeons, and continents
      (USA vs Europe). Those variations may be due to surgical techniques, training
      status, hospital and individual case volume, and, also, referral patterns and
      statistical evaluation methods. Survival times and cure rates are significantly
      improved by adjuvant chemotherapy in UICC III and in substages of UICC II (e.g.
      UICC II B) by 5%-12%, when compared with surgical controls. In three recently
      published trials standard adjuvant chemotherapy was further improved by increased
      survival rates, e.g. from 59% to 71% in stage III and IIB patients. Molecular and
      genetic factors, such as thymidylate synthase (TS), microsatellite instability
      (MSI) or loss of chromosome 18q/"DCC" might have an independent impact on
      prognosis in the spontaneous course, and TS could help to better select patients
      for adjuvant chemotherapy.

PMID- 15455235
TI  - Elastic stockings, performance and leg pain recovery in 63-year-old sportsmen.
AB  - This study was undertaken to determine whether or not elastic compression
      stockings (ECS) can be used in elderly sportsmen to increase performance and leg
      pain recovery between two maximal exercises. For 2 weeks, 12 trained elderly
      cyclists, 63 (3) years old, performed two 5-min maximal exercises, Plim1 and
      Plim2, separated by an 80-min recovery period, twice a week with a 2-day rest
      interval. During the 80-min recovery period, they randomly wore or did not wear
      grip-top ECS Ganzoni-Sigvaris. ECS exerted a 44 hPa pressure at the ankle. Blood
      lactate concentrations, hematocrit, and plasma volume were measured after a 60
      min rest and every 20 min during recovery. Leg sensations were assessed with a
      questionnaire. The decrease in maximal power between Plim1 and Plim2 was lower
      when wearing the ECS during the 80-min recovery period; when expressed as a
      percentage of Plim1, the difference reached 2.1 (1.4)%, P < 0.01. Between the two
      exercises, blood lactate concentrations and hematocrit were significantly
      decreased when wearing ECS. The increase in plasma volume was not significant.
      The 12 cyclists stated that wearing the ECS had a positive effect on their leg
      pain. Ten of the cyclists thought that it could have influenced their
      performance. However, no relationship was found between the gain in performance
      and the leg pain sensation. It was concluded that wearing ECS during an 80-min
      recovery period significantly increased subsequent performance. This was
      associated with a reduction in lactate and hematocrit.

PMID- 15455236
TI  - Acute hypervolemia does not improve arterial oxygenation in maximally exercising
      thoroughbred horses.
AB  - Recently, it was reported that acute hypervolemia improves arterial oxygen
      tension in human athletes known to experience exercise-induced arterial
      hypoxemia. Since exercise-induced arterial hypoxemia is routinely observed in
      racehorses and is known to limit performance, we examined whether pre-exercise
      induction of acute hypervolemia would similarly benefit arterial oxygenation in
      maximally exercising thoroughbred horses. Two sets of experiments, namely,
      placebo [intravenous (IV) physiological saline] and acute hypervolemia (IV 7.2%
      NaCl, causing an 18.2% expansion of plasma volume) studies were carried out in
      random order on 13 healthy, exercise-trained thoroughbred horses, 7 days apart.
      An incremental exercise protocol leading to 120 s of galloping at 14 m s(-1) on a
      3.5% uphill incline was used. Galloping at this workload elicited maximal heart
      rate and induced pulmonary hemorrhage in all horses in both treatments. In the
      placebo study, arterial oxygen tension decreased to 76.1 (2) mmHg (P<0.0001) at
      30 s of maximal exertion, but further significant changes did not occur as
      exercise duration increased to 120 s [arterial oxygen tension 72.4 (2) mmHg]. A
      significant arterial hypoxemia also developed in galloping horses in the acute
      hypervolemia study [arterial oxygen tension at 30 and 120 s was 76.7 (1.7) and
      71.9 (1.6) mmHg, respectively], but significant differences between treatments
      could not be demonstrated. In both treatments, a similar desaturation of arterial
      hemoglobin was also observed at 30 s of maximal exercise, which intensified with
      increasing exercise duration as hyperthermia, acidosis and hypercapnia
      intensified. Thus, acute expansion of plasma volume did not benefit arterial
      oxygenation in maximally exercising thoroughbred horses.

PMID- 15455237
TI  - Motor unit action potential rate and motor unit action potential shape properties
      in subjects with work-related chronic pain.
AB  - The objective of this study was to investigate differences in motor control of
      the trapezius muscle in cases with work-related chronic pain, compared to healthy
      controls. Ten cases with chronic pain and 13 controls participated in the study.
      Electromyographic (EMG) signals were recorded from the upper trapezius during
      five computer work-related tasks. Motor control was assessed using global root
      mean-square value (RMS(G)), motor unit action potential (MUAP) rate (number of
      MUAPs per second, MR) and two MUAP shape parameters, i.e. root-mean-square
      (RMS(MUAP)) and median frequency (FMED(MUAP)). MR and FMED(MUAP) were higher for
      the cases than for the controls (P < 0.05). RMS(MUAP) showed a trend for higher
      values in the chronic pain group (P < 0.13), whereas RMS(G) did not show a
      significant difference between the groups. The higher MR, FMED(MUAP) and the
      trend for higher RMS(MUAP) suggest that more high-threshold MUs contribute to low
      level computer work-related tasks in chronic pain cases. Additionally, the
      results suggest that the input of the central nervous system to the muscle is
      higher in the cases with chronic pain.

PMID- 15455238
TI  - Effect of a high-altitude expedition to a Himalayan peak (Pumori, 7,161 m) on
      plasma and erythrocyte antioxidant profile.
AB  - The effects of a high-altitude exposure were studied in six mountaineers who
      spent 3 weeks at an altitude range between 5,250 and 7,161 m after 1 week in an
      acclimatization trek (2,800-5,250 m). Blood drawn from the antecubital vein was
      collected at sea level 1 day before and 1 day after the expedition to analyse
      some haematological variables [haemoglobin (Hb), haematocrit (Htc) and red blood
      cell (RBC) count], erythrocyte antioxidant enzyme activity [superoxide dismutase
      (SOD), glutathione peroxidase (GPx) and glutathione reductase (Gr)] and membrane
      fatty acid profile [mono-unsaturated fatty acids (MUFA), polyunsaturated fatty
      acids (PUFA), saturated fatty acids (SFA), trans fatty acids (TRANS)]. Moreover,
      total antioxidant status (TAS), thiobarbituric acid reactive substances (TBARS),
      thiol protein groups (SH), SOD, GPx and Gr were measured in plasma. High-altitude
      exposure induced polycythaemia, with significant increases in RBC count (5.26%),
      Hb concentration (4.83%) and Htc (6.26%). Furthermore, a significant increase in
      plasma TBARS, SOD and Gr was observed after the expedition, whereas SH, TAS and
      GPx decreased. Erythrocyte glutathione-cycle-related antioxidant enzyme activity
      was upregulated, whereas SOD activity was maintained after the expedition. In
      addition, despite the unchanged (MUFA+PUFA)/SFA ratio, the membrane erythrocyte
      fatty acid content showed a significant increase in PUFAs and a decrease in
      TRANS, suggesting enhanced membrane fluidity. In conclusion, it seems that high
      altitude exposure, besides quantitative variations in RBC expression, induced
      plasma oxidative stress and damage, and significant changes in erythrocyte
      components, namely in antioxidant enzyme activity and membrane fatty acid profile
      that might modify RBC functionality.

PMID- 15455240
TI  - Magnification-corrected indirect biomicroscopy of the optic nerve head.
AB  - BACKGROUND: Proper use of the new Super VitreoFundus and SuperPupil XL non
      contact slit-lamp lenses for clinical disc biometry requires knowledge of their
      comparative magnification. METHODS: The optical performance of each fundus lens
      is described in terms of axial magnification, lens position, and the correction
      factor p (in degrees per millimeter) using a calibrated Gullstrand-type model eye
      adjusted for axial ametropia between -12.5 D and +12.6 D. RESULTS: The total
      change in axial magnification from myopia to hyperopia was -13.3% to +15.6%
      (Super VitreoFundus lens), and -13.9% to +14.1% (SuperPupil XL lens). When the
      fundus lens position was altered with respect to the model eye by +/-2 mm under
      myopic conditions the change in axial magnification was -5.1% to +7.7% (Super
      VitreoFundus lens), and -6.5% to +9.7% (SuperPupil XL lens). In the hyperopic
      condition the change was -3.8% to +5.8%, and -4.9% to +7.3%. Both fundus lenses
      exhibited a linear relationship between p and degree of ametropia of the model
      eye, while only the Super VitreoFundus lens displayed a constant relationship
      between p and ametropia of -5 D to +5 D. CONCLUSIONS: Using the fundus lens
      correction factor (p), the clinician may be able to estimate the dimensions of
      optic nerve head features with sufficient accuracy to allow clinical decisions to
      be made in the evaluation of patients with diagnosed or suspected glaucoma.

PMID- 15455241
TI  - Ultrasonic visualization of the effect of blinking on the lacrimal pump
      mechanism.
AB  - BACKGROUND: The role of the lacrimal sac (LS) and the medial canthal tendon in
      the lacrimal pump mechanism is controversial. This study used ultrasonic
      visualization to analyze this phenomenon. METHODS: Movements of the LS and the
      medial canthal tendon during blinking were visualized with sonography. In
      addition, the maximal profile area of the LS was measured before and after
      blinking using 15-MHz sonography in 14 individuals with a normal lacrimal
      drainage system and in six patients with lacrimal duct obstruction. RESULTS: The
      upper part of the LS could be located as an echolucent structure between the
      lacrimal bone and the medial canthal tendon. The medial canthal tendon appeared
      to compress the LS during lid closure and release the LS during lid opening. The
      measured profile area of the visible normal LS at the compression time decreased
      by 50%. The dilated LS of patients with obstruction could also be compressed by
      the orbital muscle on blinking, but the maximum area decrease was only 15.5%.
      CONCLUSION: The findings imply that the lacrimal part of the orbicularis muscle
      contracts during blinking, with the medial canthal tendon compressing the LS in a
      cranial direction. Completion of lid closure then compresses both canaliculi and
      LS, forcing the intrasacral fluid through the drainage system. The expansion of
      the LS during the opening phase of the blink causes suction, and after opening of
      the punctal areas the canaliculi and LS vacuum breaks to reload with tear fluid.
      These findings demonstrate the importance of the orbicularis muscle and the
      medial canthal tendon for the lacrimal pump mechanism during blinking.

PMID- 15455242
TI  - Detachment of the periosteum and soot staining of its underside in contact shots
      to the cerebral cranium.
AB  - Contact gunshot wounds are usually characterized by a muzzle imprint, a powder
      cavity ("pocket"), the presence of carboxyhemoglobin and often also stellate
      tears of the skin radiating from the bullet entrance hole. In shots to the
      cerebral cranium an additional sign may be observed around the bone defect: the
      periosteum is detached and reflected with soot on the underside. The frequency
      and possible causes of these periosteal findings are discussed on the basis of 68
      contact gunshot wounds from forensic autopsy material and experimental shots
      fired against the frontal bone of a slaughtered calf.

PMID- 15455243
TI  - MATP polymorphisms in Germans and Japanese: the L374F mutation as a population
      marker for Caucasoids.
AB  - Inference of the population and ancestry to which an individual belongs is
      important in forensic individualization and personal identification. In this
      study, five polymorphisms of the membrane-associated transporter protein (MATP)
      gene were investigated in German and Japanese populations. The L374F mutation was
      present at an allele frequency as high as 0.96 in the German population, whereas
      it was completely absent in the Japanese population. This extreme difference in
      allele frequency suggests that the L374F mutation is valuable as a population and
      ancestry informative marker for Caucasoids.

PMID- 15455244
TI  - Adaptive doses of irradiation-an approach to a new therapy concept for bladder
      cancer?
AB  - Radiation adaptive response in terms of induced radioresistance or
      hyperradiosensitivity, has been studied in HCV29 (human bladder epithelium) and
      RT4 (human bladder carcinoma) cell lines. After pre-irradiation doses of 0.05 Gy
      or 0.1 Gy, HCV29 cells showed induced radioresistance, whereas after pre
      irradiation doses of 0.05 Gy, 0.1 Gy, 0.2 Gy, and 0.5 Gy, the RT4 cells clearly
      showed hyperradiosensitivity. On the basis of these results, an approach has been
      developed that may lead to a concept for a new radiotherapeutic regimen of
      bladder cancer that includes protection of normal cells, on the one hand, and the
      potential of tumor cell damage, on the other hand. These findings need to be
      confirmed in further studies for the benefit of the patients.

PMID- 15455245
TI  - Local control of primary oropharyngeal malignant melanomas with limited tissue
      excision: a report of three cases.
AB  - Mucosal malignant melanomas are rare lesions, and they have different
      characteristics from their cutaneous counterparts. Since extended excisions of
      mucosal malignant melanomas located in the oropharyngeal region cause significant
      morbidity, limited surgical excision comes into consideration. Three cases of
      extensive oropharyngeal malignant melanomas were resected with 0.5-1.5-cm healthy
      tissue margins. The cases were followed for local recurrences. Case 1 applied
      radiotherapy and chemotherapy in addition to immunotherapy, and the patient is
      still alive without any local recurrences 18 months after surgery. The patient in
      case 2 underwent radiotherapy and immunotherapy and died 6 months after surgery.
      The patient in case 3 received chemotherapy in addition to immunotherapy and died
      12 months after surgery as a result of distant metastasis. All cases were without
      any local recurrences. Surgical excision with limited tumor-free tissue margins
      may be the surgery of choice to prevent morbidity associated with wide resection
      of oropharyngeal malignant melanomas if other authors also reconfirm these
      results with many more cases in the future.

PMID- 15455246
TI  - Digital rectal examination compares favourably with conventional water-soluble
      contrast enema in the assessment of anastomotic healing after low rectal
      excision: a cohort study.
AB  - BACKGROUND: Assessment of healing after low colorectal, colo-anal or ileo-pouch
      anal anastomosis is routinely performed with a water-soluble contrast enema
      (WSCE) prior to the reversal of the defunctioning stoma. Interpretation of these
      radiographs is sometimes difficult and imprecise. As these anastomoses are within
      the reach of a simple digital rectal examination (DRE), this approach is proposed
      as an effective and accurate adjunct. PATIENTS AND METHODS: This is a prospective
      cohort study recruiting patients who had undergone a low colorectal, colo-anal or
      ileo-pouch anal anastomosis with a diversion stoma. Anastomotic healing was
      assessed with a DRE in the clinic followed by the conventional WSCE. Anastomotic
      defects on digital examination and leaks on WSCEs were studied. RESULTS: There
      were 195 patients recruited with a total of 202 paired assessments from 182
      patients over 45 months. Six months after closure of the study, 174 patients had
      their stomas reversed. Thirteen examinations with WSCE showed pathology but were
      normal on digital examination (false positive rate of 6.4% for WSCE). These
      patients had their stomas reversed with no subsequent problems. Seven patients
      had an abnormal DRE but had a normal enema study (false negative rate of 3.5% for
      WSCE). These were large defects with pus and allowed the tip of the examining
      finger through. Delayed reversal of the stomas in these patients probably avoided
      continuing pelvic sepsis. The DRE was accurate in all instances except in the
      detection of a minor fistula in three patients. The sensitivity of the DRE in the
      detection of anastomotic pathology was 98.4%. CONCLUSION: The DRE yields
      additional and reliable information compared with the conventional water-soluble
      enema study in the assessment of anastomotic healing prior to stoma closure. In
      the experienced surgeon, it yielded more useful clinical information than the
      enema study.

PMID- 15455247
TI  - Triple neural tube defect--cranium bifidum with rostral and caudal spina bifida-
      live evidence of multi-site closure of the neural tube in humans.
AB  - OBJECTIVE: The coexistence of three neural tube defects (NTDs) in a single child
      is an exceptional event. A review of the literature revealed nine published
      "double" NTD cases, but no cases of "triple" NTDs have been reported to date.
      CASE REPORT: The rare case of a two-year-old boy with three distinct NTDs is
      presented. The boy had a 17x15x15-cm(3) parieto-occipital encephalocele, a small
      cervical myelomeningocele, and a 11x11x8-cm(3) thoracolumbar myelomeningocele.
      Hydrocephalus and Chiari II malformation accompanied the NTDs. All three lesions
      were surgically treated with good cosmetic results and satisfactory neurologic
      outcome. CONCLUSIONS: Current neural tube closure theories and models are
      reviewed in an attempt to better understand this extremely unusual coexistence.
      The multi-site closure model is clearly more useful in our understanding of NTDs.

PMID- 15455248
TI  - Interleukin 1beta and interleukin 6 relationship with paediatric head trauma
      severity and outcome.
AB  - BACKGROUND: Based on the known inflammatory role of interleukins (IL), we
      evaluated IL-1beta and IL-6 expressions and their association with the severity
      of traumatic brain injury (TBI; Glasgow Coma Scale [GCS]) and the outcome
      (Glasgow Outcome Score [GOS]) recorded in a paediatric population. DESIGN: The
      design was a perspective observational clinical study carried out in the
      paediatric intensive care unit of the University Hospital. METHODS: We measured
      the IL-1beta and IL-6 levels in 14 children with severe TBI (patients) and in 12
      children with obstructive hydrocephalus (control group). Cerebrospinal fluid
      (CSF) and plasma samples were collected 2 h (T1) and 24 h (T2) after TBI.
      Interleukins were assayed using the immunoenzymatic method. RESULTS: The IL-1beta
      mean level was significantly lower than the IL-6 mean level both in the CSF and
      plasma of TBI children. In the CSF, the IL-1beta level increased from 55.71+/
      72.79 pg/ml at T1 to 106.10+/-142.12 pg/ml at T2 and the IL-6 level increased
      from 405.43+/-280.28 pg/ml at T1 to 631.57+/-385.35 pg/ml at T2; a similar trend
      was observed in plasma. We found a statistically significant correlation between
      the increase in CSF and plasma interleukin levels between T1 and T2 and head
      injury severity (GCS<or=5) as well as poor outcome (GOS<or=3). CONCLUSIONS: The
      increases in IL-1beta and IL-6 expression were correlated with head injury
      severity and were indicative of poor clinical outcome, reflecting an endogenous
      neuroinflammatory response after TBI.

PMID- 15455250
TI  - Cervical meningocele in association with spinal abnormalities.

PMID- 15455253
TI  - [Characteristic features of optic nerve ganglion cells and approaches for
      neuroprotection. From intracellular to capillary processes and therapeutic
      considerations].
AB  - In many diseases associated with deterioration of the visual field and eyesight,
      optic nerve ganglion cells are at the highest risk. The clinical course of
      primary chronic open-angle glaucoma (PCOAG) is also determined by the degree of
      damage to these cells. Due to their anatomy, they are subject to extreme stress
      exerted by metabolic and microcirculatory forces. The interaction between hypoxia
      and metabolic stress leads to damage of the retinal ganglion cells. This is
      compounded by oxidative stress and age-dependent increase of advanced glycation
      end products. The following contribution gives consideration to approaches for
      delaying ganglion cell death in PCOAG, e.g., with neuroprotective agents.
      Furthermore, agents that reduce calcium influx into the cells could prevent cell
      destruction. Likewise, NMDA receptor antagonists could be effective; however,
      considerable side effects are to be feared. Antioxidants are also attributed with
      theoretical impact in combating PCOAG by preventing apoptosis. Finally, the ideal
      glaucoma medication should be well tolerated when taken orally, prevent
      destruction of retinal ganglion cells, and possess a low side effect profile.

PMID- 15455254
TI  - [Spontaneous ocular pulsation].

PMID- 15455255
TI  - The technique of ultrasound guided prostate biopsy.
AB  - This article discusses the preparations for ultrasound guided prostate biopsy,
      the conditions used and the process of performing a biopsy. The first step in
      preparing the patient is a cleansing enema before biopsy. Every author proposes
      the use of a preoperative antibiotic based prophylaxis. Differences may be found
      in the type, dosage and the duration of this preoperative application, which can
      last from 2 h to 2 days. For anaesthesia, lidocaine has been proposed, which may
      be used as a gel applied in the rectum or in the form of a prostate infiltrate.
      Quite a few colleagues administer a brief intravenous narcosis. A major debate
      goes on in respect of defining the number of biopsy samples needed. Hodge
      proposed sextant biopsy in 1989, for which we had false negative findings in 20%
      of all cases. Because of this, it has recently been suggested that eight or
      rather ten samples be taken. There are some who question even this. Twelve biopsy
      samples do offer an advantage compared to six, although in the case of eight this
      is not the case. We shall present an in depth discussion of the various opinions
      on the different numbers of biopsies samples required. For the sample site, the
      apex, the base and the middle part are proposed, and (completing the process) two
      additional samples can also be taken from the transition zone (TZ), since 20% of
      all prostate cancers originate from TZ. In case of a palpable nodule or any
      lesion made visible by TRUS, an additional, targeted, biopsy has to be performed.
      Certain new techniques like the 3-D Doppler, contrast, intermittent and others
      shall also be presented. The control of the full length of samples taken by a
      gun, as well as the proper conservation of the samples, are parts of pathological
      processing and of the technical tasks. A repeated biopsy is necessary in the case
      of PIN atypia, beyond which the author also discusses other indications for a
      repeated biopsy. We may expect the occurrence of direct postoperative
      complications and it is necessary to know how to treat these.

PMID- 15455256
TI  - Health-related quality of life of Japanese patients with overactive bladder
      treated with extended-release tolterodine or immediate-release oxybutynin: a
      randomized, placebo-controlled trial.
AB  - Overactive bladder (OAB) has a significant impact on a patient's health-related
      quality of life (HRQoL). This study assessed the HRQoL of Japanese OAB patients
      following 12 weeks' treatment with tolterodine extended release (ER) or
      oxybutynin. A total of 293 patients with symptoms of OAB were randomized for
      treatment with tolterodine ER 4 mg once daily (n=114), oxybutynin 3 mg three
      times daily (n=122) or a placebo (n=57). Treatment efficacy and safety
      assessments were made over the 12-week period. HRQoL was assessed using the
      King's Health Questionnaire (KHQ). Patients receiving tolterodine ER or
      oxybutynin showed a significant (P<0.05) improvement in the Incontinence Impact,
      Role Limitations and most other KHQ domains compared with the placebo. These
      changes in HRQoL corresponded with significant (P<0.05) improvements in
      micturition diary variables for patients receiving tolterodine ER and oxybutynin
      compared with placebo. Our findings demonstrate that Japanese OAB patients
      receiving tolterodine ER or oxybutynin experienced overall improvement in their
      quality of life.

PMID- 15455257
TI  - An efficient transformation system for chickpea (Cicer arietinum L.).
AB  - A reproducible and efficient transformation method was developed for Desi and
      Kabuli chickpeas (Cicer arietinum L.) using germinated seedlings as sources of
      explants. Slices derived from plumules were the most efficient at generating
      transformed shoots. The AGL1 Agrobacterium-treated explants were first incubated
      on thidiazuron-containing media, then selected using phosphinothricin. Resistant
      shoots were successfully transferred to soil either by grafting or in vitro
      rooting. In experiments each taking 4-9 months, a total of 41 confirmed
      transformed lines were created using embryo axis slices as source explants,
      giving a transformation frequency of 5.1%. Southern analysis and histochemical
      and leaf painting assays demonstrated integration and expression of the
      transgenes in the initial transformants and two generations of progeny.

PMID- 15455258
TI  - Effects of boron deficiency in cell suspension cultures of Populus alba L.
AB  - Cell suspension cultures of Populus alba L. (original cells) require at least 10
      microM boron for appropriate growth. Using original cells we established a cell
      line, T-5B, which can grow in a medium containing low levels of boron (5 microM).
      The level of boron localized in the cell walls of T-5B cells was one-half that
      found in the cell walls of original cells maintained in medium containing 100
      microM boron, and the level of the rhamnogalacturonan II dimer, cross-linked by a
      borate ester, also decreased in the former. The sugar composition of whole cell
      walls of the T-5B cell line was similar that of the original cells, however
      pectic polysaccharides composed of arabinose or galacturonic acid were easily
      extracted from T-5B cell walls with 50 mM trans-1,2-cyclohexanediamine-N,N,N',N'
      tetraacetic acid. Our results suggest that boron deficiency causes a weakening of
      the interaction among pectic polysaccharides due to a decrease in boron
      rhamnogalacturonanII cross-linkage.

PMID- 15455259
TI  - Induction of vascular endothelial growth factor and matrix metalloproteinase-3
      (stromelysin) by interleukin-1 in human articular chondrocytes and synoviocytes.
AB  - We investigated the effects of interleukin (IL)-1 on vascular endothelial growth
      factor (VEGF) and matrix metalloproteinase-3 (MMP-3) (stromelysin) secretion from
      chondrocytes and synoviocytes in different clinical conditions. Specifically,
      cells obtained from osteoarthritic (OA) (n = 7), rheumatoid arthritic (RA) (n =
      5), and post-traumatic (PT) (n = 5) patients were stimulated in vitro with IL
      1beta in the presence or absence of an IL-1 receptor antagonist (IL-1ra)
      (anakinra). Levels of secreted MMP-3 and VEGF were measured by enzyme-linked
      immunosorbent assay. The VEGF mRNA expression was analyzed quantitatively.
      Interleukin-1 induced both VEGF and MMP-3 secretion from all of the samples
      tested, and VEGF mRNA expression was also upregulated. Interleukin-1ra
      significantly suppressed the enhancing effect of IL-1 on MMP-3 and VEGF in both
      cell types. In conclusion, IL-1 simultaneously induces MMP-3 and VEGF production
      from chondrocytes and synoviocytes in inflammatory, degenerative, and post
      traumatic joints. Therefore, IL-1ra might be beneficial for protection from VEGF
      mediated alterations of cartilage metabolism in pathologic and physiologic
      conditions.

PMID- 15455260
TI  - Pasteurella multocida toxin as a tool for studying Gq signal transduction.
AB  - Pasteurella multocida toxin (PMT) stimulates and subsequently uncouples
      phospholipase C (PLC) signal transduction through its selective action on the
      Galphaq subunit. This review summarizes what is currently known about the
      molecular action of PMT on Gq and the resulting cellular effects. Examples are
      presented illustrating the use of PMT as a powerful tool for dissecting the
      molecular mechanisms involving pertussis toxin (PT)-insensitive heterotrimeric G
      proteins.

PMID- 15455261
TI  - Basal ganglia haematomas in non-comatose patients: subacute stereotactic
      aspiration improves long-term outcome in comparison to purely medical treatment.
AB  - This study examined whether subacute stereotactic evacuation of basal ganglia
      haematomas in primarily non-comatose patients is suitable to improve the ultimate
      outcome of this subgroup of stroke patients. Applying rigorous selection
      criteria, 56 consecutive non-comatose patients with ganglionic haematomas were
      treated stereotactically, and 1-year outcomes employing four outcome parameters
      commonly used to assess outcome were compared with those of 39 similar patients
      who were treated purely medically. No survival benefit was found in long-term
      follow-up for either surgical or conservative treatment (total mortality 16.1% vs
      28.2%; P=0.121). Among survivors, however, outcome was significantly better in
      surgical patients. Compared with medical patients, the median Glasgow Outcome
      Scale score was 1 point higher (P<0.0001) in surgical patients, and the median
      European Stroke Scale score improvement from baseline to 1-year score was
      significantly better (P<0.0001). Accordingly, the median Barthel Index score was
      significantly higher (P=0.002), and the median Modified Rankin Scale score was 1
      point lower (P<0.0001). We conclude that primarily non-comatose patients with
      basal ganglia haematomas can ultimately profit from this form of minimally
      invasive treatment.

PMID- 15455262
TI  - Empirical Bayes estimation of gene-specific effects in micro-array research.
AB  - Micro-array technology allows investigators the opportunity to measure expression
      levels of thousands of genes simultaneously. However, investigators are also
      faced with the challenge of simultaneous estimation of gene expression
      differences for thousands of genes with very small sample sizes. Traditional
      estimators of differences between treatment means (ordinary least squares
      estimators or OLS) are not the best estimators if interest is in estimation of
      gene expression differences for an ensemble of genes. In the case that gene
      expression differences are regarded as exchangeable samples from a common
      population, estimators are available that result in much smaller average mean
      square error across the population of gene expression difference estimates. We
      have simulated the application of such an estimator, namely an empirical Bayes
      (EB) estimator of random effects in a hierarchical linear model (normal-normal).
      Simulation results revealed mean-square error as low as 0.05 times the mean
      square error of OLS estimators (i.e., the difference between treatment means). We
      applied the analysis to an example dataset as a demonstration of the shrinkage of
      EB estimators and of the reduction in mean-square error, i.e., increase in
      precision, associated with EB estimators in this analysis. The method described
      here is available in software that is available at
      http://www.soph.uab.edu/ssg.asp?id=1087.

PMID- 15455263
TI  - Comprehensive association analysis of APOE regulatory region polymorphisms in
      Alzheimer disease.
AB  - Several recent case-control studies have examined the association between single
      nucleotide polymorphisms (SNPs) in the promoter region of the apolipoprotein E
      gene (APOE) and risk of Alzheimer disease (AD), with conflicting results. We
      assessed the relation between five APOE region SNPs and risk of AD in both case
      control and family-based analyses. We observed a statistically significant
      association with the +5361T allele in the overall case-control analysis (P
      value=0.04) after adjusting for the known effect of the APOE-4 allele. Further
      analysis revealed this association to be limited to carriers of the APOE-4
      allele. Age-stratified analyses in the patients with age at onset of 80 years or
      greater and age-matched controls showed that the -219T allele (P value=0.009) and
      the +113C allele (P value=0.03) are associated with increased risk of AD. Despite
      these findings, haplotype and family-based association analyses were unable to
      provide evidence that the APOE region SNPs influenced risk of AD independent of
      the APOE-4 allele. In addition to risk, we tested for association between the
      SNPs and age at onset of AD, but found no association in the case-control or
      family based analyses. In conclusion, SNPs +5361, or a SNP in strong linkage
      disequilibrium, may confer some additional risk for developing AD beyond the risk
      due to APOE-4; however, the effect independent of APOE-4 is likely to be small.

PMID- 15455264
TI  - Fine mapping of 16q-linked autosomal dominant cerebellar ataxia type III in
      Japanese families.
AB  - The autosomal dominant cerebellar ataxias (ADCAs) are a clinically and
      genetically heterogeneous group of disorders. To date, at least 11 genes and 13
      additional loci have been identified in ADCAs. Despite phenotypic differences,
      spinocerebellar ataxia 4 (SCA4) and Japanese 16q-linked ADCA type III map to the
      same region of 16q22.1. We report four Japanese families with pure cerebellar
      ataxia and a disease locus at 16q22.1. Our families yielded a peak lod score of
      6.01 at marker D16S3141. To refine the candidate region, we carried out genetic
      linkage studies in four pedigrees with a high density set of DNA markers from
      chromosome 16q22.1. Our linkage data suggest that the disease locus for 16q-ADCA
      type III is within the 1.25-Mb interval delineated by markers 17msm and CTTT01.
      We screened for mutations in 36 genes within the critical region. Our critical
      region lies within the linkage interval reported for SCA4 and for Japanese 16q
      ADCA type III. These data suggest that the ADCA that we have characterized is
      allelic with SCA4 and Japanese 16q-linked ADCA type III.

PMID- 15455265
TI  - Effects of melatonin on acute necrotizing pancreatitis in rats.
AB  - The aim of this study was to investigate the influence of melatonin on acute
      necrotizing pancreatitis (ANP) induced by glycodeoxycholic acid in rats. The
      induction of ANP resulted in significant increases in mortality rate, pancreatic
      necrosis and increased serum activity of amylase, alanine aspartate transferase
      (ALT), interleukin 6 (IL-6), lactate dehydrogenase (LDH) in bronchoalveolar
      lavage (BAL) fluid, serum concentration of urea, tissue activity of
      myeloperoxidase (MPO) and malondialdehyde (MDA) in the pancreas and lung, and
      significant decrease of concentrations of calcium, blood pressure, urine output
      and pO (2). Melatonin inhibited the changes in blood pressure, urine output, pO
      (2), serum concentration of urea, and calcium, tissue activity of MPO and MDA in
      the pancreas and lung, LDH level in BAL fluid, and partially reduced serum
      activity of IL-6. Melatonin did not change serum activity of amylase, ALT,
      pancreatic damage and the mortality rate. The use of melatonin has a limited
      value on the course of ANP. It may be useful as a supportive treatment during
      ANP.

PMID- 15455266
TI  - [Intestinal wall vascularisation in Crohn's disease].
AB  - BACKGROUND AND AIMS: In a pilot study the semi-quantitative classification of
      intestinal wall vascularisation as proposed by Limberg was evaluated. PATIENTS
      AND METHODS: 20 patients with confirmed Crohn's disease and clinical activity (10
      male, 10 female, mean age 30.0 +/- 7.72 years, range 21 - 49 years, mean time
      since onset of disease 4.6 years, range 0 - 15 years) were included. CDAI, CRP,
      ESR, and the blood count were evaluated. Two and six weeks after inclusion into
      the study these examinations were repeated. All patients were treated with anti
      inflammatory drugs. The intestinal wall thickness was measured with ultrasound.
      The vascularisation following the Limberg classification and the number of blood
      vessels per square centimetre were assessed in the power-Doppler mode. RESULTS:
      The mean length of bowel segments with increased wall thickness (> 3 mm) at the
      beginning of the study was 20.3 cm (range 5 - 50 cm), the mean intestinal wall
      diameter 5.9 mm (range 4 - 9 mm). The mean density of blood vessels in the power
      Doppler mode was 3.8 vessels/cm (2) (range 0 - 8 vessels/cm (2)), the median of
      Limberg levels was 2 (range 1 - 4). The density of blood vessels per cm (2) well
      correlated with the Limberg classification throughout the study (r = 0.2 at
      start; r = 0.94 at 1st follow-up; r = 0.91 at 2nd follow-up). CONCLUSION: The
      classification for measuring intestinal wall vascularisation semi-quantitatively
      (as proposed by Limberg) proved to be easily applicable in routine sonography.
      Besides the measurement of intestinal wall thickness, activity indices, clinical
      and laboratory parameters, it may constitute an additional means for evaluation
      of disease activity.

PMID- 15455267
TI  - [Diagnosis and therapy of ulcerative colitis: results of an evidence based
      consensus conference by the German society of Digestive and Metabolic Diseases
      and the competence network on inflammatory bowel disease].

PMID- 15455268
TI  - [Methodological basis for the development of consensus recommendations].

PMID- 15455269
TI  - [Ulcerative colitis. Clinical diagnosis].

PMID- 15455270
TI  - [Ulcerative colitis. Histological diagnosis].

PMID- 15455271
TI  - [Ulcerative colitis. Acute episode].

PMID- 15455272
TI  - [Ulcerative colitis. Nutrition].

PMID- 15455273
TI  - [Ulcerative colitis. Fulminant disease].

PMID- 15455274
TI  - [Ulcerative colitis. Chronic active course].

PMID- 15455275
TI  - [Ulcerative colitis. Maintenance therapy].

PMID- 15455276
TI  - [Ulcerative colitis. Cancer prevention].

PMID- 15455277
TI  - [Surgery in ulcerative colitis].

PMID- 15455278
TI  - [Pouchitis].

PMID- 15455279
TI  - [Extraintestinal manifestations in ulcerative colitis].

PMID- 15455280
TI  - [Immunosuppressive therapy for inflammatory bowel disease: consensus by the
      Austrian working group on IBD].
AB  - Azathioprine (AZA) or 6-mercaptopurine (6-MP) are the immunosuppressive drugs of
      choice in the treatment of inflammatory bowel disorders (IBD). Optimal dosage for
      AZA is around 2.5 mg/kg body weight and induction of remission by these drugs may
      take 6 - 7 months. Intramuscularly applied Methotrexate (MTX) is the second
      choice, while its efficacy starts earlier than that of AZA; studies assessing
      oral low-dose MTX treatment are lacking. Cyclosporin is the standard treatment in
      case of steroid-refractory severe ulcerative colitis. This drug may also be used
      in patients with severe extraintestinal manifestations of IBD. Regarding other
      immunosuppressive drugs such as mycophenolic acid or 6-thioguanine respective
      controlled clinical study data are not available. The risk of malignancy using
      immunosuppressive drugs such as AZA is low and furthermore, especially AZA and 6
      MP can be used rather safely during pregnancy.

PMID- 15455281
TI  - [Ulcerative colitis. Psychosomatics].

PMID- 15455282
TI  - [Ulcerative colitis. Complementary therapies].

PMID- 15455284
TI  - [Identification of elevated carbohydrate-deficient transferrin (CDT) serum level
      as transferrin (Tf)-D-variant by means of isoelectric focusing].
AB  - Many studies have shown carbohydrate-deficient transferrin (CDT) to be a
      sensitive and specific marker of chronic alcohol abuse. We present the case of a
      23-year-old, healthy professional soccer player who caused a car accident due to
      alcohol consumption. Several CDT test results were elevated above the laboratory
      reference range and were considered to be caused by alcohol intake at a level
      commensurate with misuse and thus license reapplication was refused. In addition,
      assuming chronic alcohol abuse, the young man suffered from increasing social
      isolation. He was finally referred to our out-patient clinic for further
      evaluation on the assumption of a liver disease. Since chronic alcohol
      consumption was denied, and there was no evidence of liver disease, a qualitative
      characterization of the transferrin isoforms was performed. Isoelectric focusing
      of serum transferrin revealed a pattern atypical for chronic alcohol intake but
      detected a genetically determined transferrin (Tf)-D-variant. The changed amino
      acid sequence caused an overlapping of transferrin isoforms with different
      degrees of sialylation, thus revealing false-positive serum CDT values.
      Determination of this Tf-D-variant heterozygosity resulted in his social
      rehabilitation and license reinstatement. Thus, where the evidence for alcohol
      dependency is either uncertain or uncorroborated, qualitative isoelectric
      focusing of transferrin is a useful method for analyzing unexplained CDT
      elevations, thus increasing the value of CDT as a marker for chronic alcoholic
      abuse.

PMID- 15455285
TI  - [Acute liver failure caused by phenprocoumon -- three case reports].
AB  - We report on three women with phenprocoumon-induced liver failure. In all three,
      jaundice was the main symptom. Liver failure was manifest 6 months after initial
      exposure to phenprocoumon in two women and 18 months in the third. None received
      corticosteroids. The course was prolonged in each patient, but all three finally
      recovered. Liver failure associated with oral anticoagulation is rare. Most
      published reports describe only individual cases. Instances of fatal outcome and
      instances requiring liver transplantation for survival have been seen. Coumarin
      treatment should be considered as a possible etiology of acute liver failure,
      even if the drug has been administered for a longer period without any previous
      problems. While cross-reactions with other coumarin substances have been
      reported, if coumarin anticoagulation is absolutely required, use of a congener
      under close monitoring seems justifiable.

PMID- 15455286
TI  - Doppler sonography in inflammatory bowel disease.
AB  - The course of chronic inflammatory bowel diseases is highly variable and
      prediction of relapse remains difficult. Doppler sonography is a newer, non
      invasive method to assess the hyperdynamic splanchnic blood flow that is
      characteristic of acute inflammation. Its role in the analysis of disease
      activity is still limited and its application restricted to specialized units.
      However, improved spatial resolution by power Doppler ultrasound, with or without
      the use of contrast agents, allows a very early detection of mucosal and
      transmural inflammatory lesions. Still more important, the repeated
      quantification of mesenteric blood flow enables the prediction of relapse at six
      months after steroid-induced remission. Future studies should clarify whether the
      combined application of available methods will allow a more calculated and
      finally more effective therapy.

PMID- 15455287
TI  - [Gastrointestinal lymphomas].
AB  - Based on new insights into aetiology and pathogenesis of gastrointestinal
      lymphomas and their histomorphological and molecular characteristics, important
      progress in their diagnostics and therapy has been made during recent years. The
      WHO has established an internationally accepted classification of
      gastrointestinal lymphomas. Although not considered therein, from the clinical
      point of view a differentiation between low- and high-grade lymphomas would seem
      to be helpful as the grade of malignancy and stage directly determine the
      therapeutic strategy. Therefore, a thorough endoscopic-bioptic technique (gastric
      mapping) and careful clinical staging is necessary. The latter should always
      include endoscopic ultrasound. Helicobacter pylori represents the decisive causal
      factor for gastric MALT lymphomas while untreated sprue is an established risk
      factor for intestinal T cell lymphomas. The therapeutic spectrum ranges from
      Helicobacter pylori eradication therapy to the well known oncological modalities,
      namely chemotherapy, radiation or surgery and their combined use. However, also a
      watch-and-wait strategy may be a good choice in the individual case (minimal
      residual disease after successful Helicobacter pylori eradication or disseminated
      stages of indolent lymphomas not offering a curative option).

PMID- 15455291
TI  - Environmental characteristics and sleep in two-month-old infants.
AB  - The study aimed at assessing possible relationship between the quality of infant
      environment and maternal reported behavioural features during sleep in 2-month
      old infants. It comprised 115 randomly selected, apparently healthy infants (50
      boys, 65 girls) from community setting who were singletons born at term with
      normal birth weight in St. Petersburg in 2001-2002. Quality of infant care was
      estimated using the "PROCESS" (Paediatric Review of Children's Environment
      Support and Stimulation) inventory enabling to measure infant's developmental
      stimulation and organisation. Infant's behaviour during sleep was assessed using
      an adapted version of the Children's Sleep Habits Questionnaire (CSHQ). The
      babies facing more developmental stimulation and from more organised environment
      less often fell asleep in parents bed (P = 0.036). Infants from more organised
      environment were more often put to sleep at the same time at night, more often
      were ready to go to sleep at bedtime and less often struggled at bed; it was more
      common with them to have right amount of sleep and to have about a same amount of
      sleep each day; less often they moved a lot during sleep and woke up in sleep.
      These associations remained significant after adjustment has been made for each
      of such potential confounders as infant's gender, weight at birth and at study,
      gestational age, Apgar score at 1 and 5 minutes, birth order, maternal age and
      education, maternal marital status, infant's feeding at birth and at study, as
      well as to their simultaneous effects. Lower environmental organisation and
      developmental stimulation may be associated with specific disadvantageous infant
      behavioural features during sleep. Infants with parentally reported sleep
      problems should be carefully considered for possible flaws in the quality of
      environment.

PMID- 15455292
TI  - [The VIP-secreting tumor as a differential diagnosis of protracted diarrhea in
      pediatrics].
AB  - BACKGROUND: Vasoactive intestinal peptide (VIP) can be produced by mature
      neurogenic tumors. Pathologically elevated VIP plasma levels cause secretory
      diarrhea with excessive loss of water and electrolytes. Despite the clinical
      severity diagnosis of a VIP-secreting tumor is often delayed and subsequently its
      extirpation as the mainstay of therapy. PATIENTS: We report on two patients with
      ganglioneuroblastoma and secretory diarrhea. We contrast the case of a 13-month
      old boy with advanced symptoms of secretory diarrhea, high VIP plasma levels, and
      late diagnosis to the case of a 14-month-old boy with mild secretory diarrhea and
      normal VIP plasma levels but positive proof of VIP in tumor tissue. Reviewing the
      literature we found 57 cases of pediatric VIP-secreting tumors. RESULTS: The
      clinical situation is characterized by the typical symptoms of secretory diarrhea
      with hypokalemia and metabolic acidosis. Histopathology predominantly reveals
      ganglioneuroblastoma or ganglioneuroma. The symptoms mostly stop after complete
      resection of the tumor whereas lack of resection is associated with elevated
      mortality rates. CONCLUSIONS: In case of prolonged therapy-resistant secretory
      diarrhea the existence of a VIP-secreting tumor should be considered. Diagnostic
      work-up should include the assessment of VIP plasma levels, catecholamines in
      urine, and appropriate imaging techniques in order to rule out or confirm the
      possibility of a VIP producing tumor.

PMID- 15455293
TI  - [Management of multiple endocrine neoplasia syndrome type 2 families in
      association with rare germline mutations of the RET proto-oncogene].
AB  - INTRODUCTION: Heredity of MEN2 syndromes is caused by a heterozygous germline
      mutation in the RET proto-oncogene. This study describes families with rare
      noncysteine codon 790/791 mutations and discusses the genotype-phenotype
      correlation plus the therapeutic options. PATIENTS AND METHODS: Forty-five
      patients with a putative sporadic MTC were screened for RET germline mutations by
      direct DNA sequencing. Family members of identified index cases underwent genetic
      analysis. Gene carriers were examined clinically and biochemicaly and underwent
      prophylactic thyroidectomy. RESULTS: Five index patients were identified. In the
      kindreds three L790F and one Y791F carriers were detected. The thyroid gland
      histology of L790F carriers revealed MTC in 2 patients and C-cell hyperplasia in
      2 additional patients. The Y791F carrier had a normal histology. CONCLUSIONS:
      Codon 790/791 mutations had diverse penetrance: prophylactic thyreoidectomy in
      children is a justifiable approach for codon 790 mutation carriers, but should
      depend on the clinical course of codon 791 carriers.

PMID- 15455294
TI  - [The ketogenic diet in German-speaking countries: update 2003].
AB  - BACKGROUND: The ketogenic diet has been used for decades to treat intractable
      childhood epilepsies. It is also the treatment of choice for GLUT1 deficiency
      syndrome and pyruvate-dehydrogenase-complex-deficiency. Recent studies have once
      again confirmed the efficiacy of the diet, but the diet is hardly known in Europe
      and has never been quite accepted as an effective treatment of childhood
      epilepsy. PATIENTS: We report retrospective data on 146 children treated with the
      ketogenic diet in Austria, Switzerland, and Germany. METHOD: In 2000 and 2002,
      standardized questionaires were sent to 13 neuropediatric departments to evaluate
      indications, effects and side effects. RESULTS: In children with refractory
      epilepsy (n = 111), 8 % became seizure-free on the diet. Seizure reduction of >
      90 % was achieved in additional 9 % of patients, a seizure reduction of 50-90 %
      in additional 14 % of patients. There was a great variability between epilepsy
      departments. All patients with GLUT1 deficiency syndrome (n = 18) and pyruvate
      dehydrogenase-complex-deficiency (n = 15) showed clinical improvement. In GLUT1
      deficiency syndrome, complete seizure control was achieved in 94 % of patients.
      Compliance was good in 82 % of all patients regardless of the indication for the
      diet. CONCLUSION: In contrast to the general restraint towards the ketogenic diet
      in Europe, our data supports its effectiveness as the treatment of choice for
      GLUT1-deficiency syndrome und pyruvate-dehydrogenase-complex-deficiency. In
      children with refractory epilepsy, the ketogenic diet matched the effect of most
      anticonvulsants and was well tolerated. These data and two workshops resulted in
      recommendations for the use of the ketogenic diet in children as a basis for a
      general diagnostic and therapeutic standards to compare and improve the use of
      the ketogenic diet in Europe.

PMID- 15455295
TI  - ["Real time"-3D-echocardiography: a valuable new tool in preoperative assessment
      of complex cardiac defects].
AB  - Evaluating complex cardiac defects in small children preoperatively requires
      multiple diagnostic procedures including echocardiography, but also the invasive
      methods such as cardiac catheterisation, computer-tomography and magnetic
      resonance imaging. We tried to assess the complex anatomy of the atrioventricular
      valves in atrioventricular septal defect using bedside real-time three
      dimensional echocardiography and comparing these results to the anatomic findings
      at the time of operation.

PMID- 15455296
TI  - [Severe drug-related skin reaction: toxic epidermal necrolysis caused by
      carbamazepine].
AB  - BACKGROUND: Drug-related skin reactions often present as macular, maculopapular
      or urticarial rashes. Severe drug eruptions are rare, with life-threatening
      events occurring in about 4 per one million persons a year. In pediatric patients
      the estimated incidence of Stevens-Johnsons-syndrome (SJS) and toxic epidermal
      necrolysis (TEN) is even lower. They are often caused by antiepileptic drugs like
      carbamazepine. CASE REPORT: A 10 (5)/ (12) year old boy of dark complexion
      suddenly developed a severe bullous skin disease six weeks after starting
      carbamazepine therapy due to focal epilepsy. Within few hours a life-threatening
      systemic inflammatory reaction occurred with subsequent respiratory failure. The
      clinical course was complicated by bacterial sepsis, bilateral thrombosis of the
      external iliacal veins and bilateral ocular symblephara. The skin healed with
      considerable pigmentary disturbance. We report the differential diagnostic and
      therapeutical features of toxic epidermal necrolysis and give a review of the
      literature.

PMID- 15455297
TI  - Hydropericardium causing sudden infant death in glycogenosis type I: osmotic
      injury due to percutaneous silastic catheterization.
AB  - BACKGROUND: The aim of this case report and the review of the literature is to
      demonstrate dangers when using peripherial silastic catheters in preterm and term
      newborns or infants. PATIENT, METHODS AND RESULTS: We report on a female infant
      with glycogenosis type I a (MIM 232200) due to glucose 6-phosphatase deficiency
      (homozygosity for R170X) and sudden infant death at the age of 9 months due to a
      rare catheter complication (hydropericardium with tamponade without perforation).
      CONCLUSION: We believe that this fatal complication was caused by local osmotic
      dysbalance due to direct contacts between atrial wall and the catheter tip. There
      is no relation known between patients with inborn errors of metabolism
      complicated by metabolic derangement and higher incidences of mechanical or non
      mechanical catheter complications.

PMID- 15455298
TI  - Coxsackie virus B 4 encephalitis in a 7 year old boy.
AB  - BACKGROUND: Enteroviruse belongs to the family of picornaviruses. They can be
      devided in 4 groups: polioviruses (Typ 1-3) enteric cythopathogenic human orphan
      (ECHO)- viruses, unclassified enteroviruses 68-71 and coxsackie viruses.
      Coxsackie virus type B can cause pharyngitis, myalgia, myocarditis and meningitis
      as well as severe neonatal infections. CASE REPORT: We report a patient with
      coxsackie type B 4 encephalitis. A 7 year old boy had 2 episodes of mental
      dizziness and consciousness disturbance. Because of he presented a visus of 70 %,
      headaches and vomiting he was admitted to our hospital. In the cerebrospinal
      fluid a coxsackie virus type B 4 could be identified. With nonspecific therapy
      the boy recovered. CONCLUSION: We concluded that coxsackie virus B 4 caused acute
      encephalitis with ophthalmological and mental symptoms and good prognosis.
      Coxsackie virus B 4 should be considered in patients with encephalitis.

PMID- 15455299
TI  - [Target-oriented tumor therapy -- proof of the principle].

PMID- 15455300
TI  - [Expression profile and prognostic significance of CD24, p53 and p21 in
      lymphomas. A tissue microarray study of over 600 non-Hodgkin lymphomas].
AB  - BACKGROUND AND OBJECTIVE: Tissue microarrays allow the simultanous, rapid and
      standardized in-situ analysis of up to 1000 different tissue samples on a single
      glass slide. We investigated the expression profil and the prognostic
      significance of CD24, p53 and p21 using a Non-Hodgkin-Lymphoma tissue microarray.
      METHODS: Over 600 well documented Non-Hodgkin-Lymphomas, consisting of 341
      diffuse large B-cell lymphomas, 86 follicular lymphomas, 81 chronic lymphatic
      leukemias/small lymphocytic lymphomas, 51 primary mediastinal diffuse large B
      cell lymphomas, 26 mantle cell lymphomas, 8 lymphoplasmocytic lymphomas, 8 T-cell
      lymphomas NOS und 2 Burkitt lymphomas were brought into array format. The
      expression of CD24, p53 and p21 was analysed semiquantitatively by
      immunohistochemistry. The immunophenotype p53+/p21- (Deltap53) was used as a
      surrogat for p53 gene mutations. The expression profile was compared to clinical
      data and the overall survival in the subgroup of diffuse large B-cell lymphomas.
      RESULTS: 91% of the analyzed Non-Hodgkin-lymphomas (473 of 522 cases) showed CD24
      positivity. CD24 Expression was not associated with survival. Deltap53 was found
      in thirteen percent of all lymphomas (70 of 539 cases), the subgroup of the
      diffuse large B-cell lymphomas demonstrated the highest Deltap53 (21%). In a
      multivariate cox regression analysis, a high international prognostic index and
      Deltap53 were independent markers of bad survival. CONCLUSION: The TMA-technology
      allows also in lymphoma research the simultanous, cost-effective and standardized
      analysis of large patient cohorts. Deltap53 revealed as an independent negative
      prognostic factor in diffuse large B-cell lymphomas. It can easily be determined
      in daily routine practice.

PMID- 15455301
TI  - [An alternative Abl-kinase inhibitor overcomes imatinib resistance mutations of
      Bcr-Abl oncogenes].
AB  - BACKGROUND AND OBJECTIVE: The tyrosinkinase inhibitor Imatinib is active in
      Philadelphia-positive (Ph+) leukemia. Mutations within the Bcr-Abl kinase domain
      represent the major cause for clinical resistance toward imatinib. We aimed to
      examine, whether the alternative Abl Kinaseinhibitor SKI-DV 2 - 43 may be capable
      of suppressing the growth of cells expressing mutant forms of Bcr-Abl. METHODS:
      The proliferation of cells expressing wild-type and mutant forms of Bcr-Abl was
      measured in the presence of imatinib or the pyrido-pyrimidine SKI-DV 2 - 43.
      RESULTS: The growth of a cell line expressing wild-type Bcr-Abl was suppressed
      with higher potency in the presence of SKI-DV 2 - 43 when compared to imatinib.
      Moreover, SKI-DV 2 - 43 effectively suppressed mutant forms of Bcr-Abl that cause
      imatinib resistance in patients. CONCLUSION: Therefore, alternative Abl kinase
      inhibitors might play an important role in the future therapy of Philadelphia
      positive leukemias.

PMID- 15455302
TI  - [Complete remission of an idiopathic hypereosinophilic syndrome while using
      imatinib].
AB  - HISTORY AND ADMISSION FINDINGS: A 47-year-old man with a hypereosinophilic
      syndrome (HES), which has been known for 20 years, was admitted to our department
      due to insufficient therapeutic response to hydroxyurea. In general, the patient
      felt well, but reported increasing neurological problems, such as ataxia, memory
      deficits and dysarthria. INVESTIGATIONS: Bone marrow assessments corroborated the
      diagnosis of a HES. However, we were not able to detect the insertional deletion
      4q12 with concomitant fusion of the FIP1L1 to the PDGFRA locus. Magnetic
      resonance imaging (MRI) indicated a granulomatous vasculitis, which was most
      likely due to the hematologic malignancy. TREATMENT AND COURSE: : Despite
      negativity for the FIP1L1-PDGFRA fusion gene, therapy was started with the
      tyrosine kinase inhibitor Imatinib. This led to a rapid normalization of
      eosinophilic granulocytes in the peripheral blood as well as in the bone marrow.
      In addition, the neurologic symptoms substantially improved. CONCLUSION: Imatinib
      provides a potent therapeutic option in FIP1L1-PDGFRA negative patients suffering
      from HES.

PMID- 15455303
TI  - [New diagnostic and therapeutic strategies for aggressive lymphomas].

PMID- 15455304
TI  - [Advances in palliative and adjuvant chemotherapy of colon cancer].

PMID- 15455305
TI  - [Therapy of chronic myelogenous leukemia in 2004].
AB  - Chronic myelogenous leukemia constitutes a clinical model for other neoplastic
      diseases. The cytogenetic hallmark of CML, the Ph chromosome with the molecular
      juxtaposition of BCR and ABL genes and the multistep pathogenesis with the stable
      chronic phase, the accelerated phase and the terminal blast crisis provide the
      background for the translation of molecular-cytogenetic findings into clinical
      practice. The systematic development of the selective BCR-ABL inhibitor imatinib
      was based on the discovery of the molecular pathogenesis of CML. Promising
      preclinical data were confirmed in phase I-III trials. Concerning hematologic and
      cytogenetic response and adverse effects imatinib is superior to interferon
      alpha. Open questions are treatment duration in patients with good response, long
      term side effects, persistence of minimal residual disease in almost all
      patients, development of resistance after long term therapy, and the efficacy of
      combination treatments. Prospective clinical trials, e. g. CML study IV of the
      German CML Study Group, should answer these questions. The impact of the various
      treatment modalities (imatinib, interferon alpha, ara-C, allogeneic stem cell
      transplantation) will be elucidated. The recruitment of newly diagnosed CML
      patients into CML-study IV is recommended.

PMID- 15455306
TI  - [Preoperative cardiovascular risk evaluation. Comment on the article from DMW
      22/2004].

PMID- 15455307
TI  - Robot-assisted remote surgery: technological advances, potential complications,
      and solutions.
AB  - Technical limitations, mostly related to the issue of time delay for transmission
      of digitized information, had prevented the development of remote surgery
      intended as performance of a complete surgical procedure from long distances. To
      overcome the issue of time delay, tests and researches performed with the joined
      effort of surgeons, robotic and telecommunication engineers convinced our group
      that use of the high-speed terrestrial network [asynchronous transfer mode (ATM)
      service], rather than satellite connections, would significantly reduce the time
      lag for transmission of data. Using ATM technology, our group demonstrated the
      feasibility of performing surgery across transoceanic distances by safely
      carrying out a laparoscopic cholecystectomy, first on an animal model and later
      (September 7, 2001), on a patient. Using ATM technology, the mean time lag for
      transmission of data and images was 155 msec despite a total round-trip distance
      of 14,000 km. Teletransmission of active surgical manipulations have the
      potential to ensure availability of surgical expertise in remote locations for
      difficult or rare operations, and improve surgical training worldwide. However,
      several limitations remain for remote surgery to become commonplace. Among these,
      the need to render ATM network available to hospitals, costs of technology,
      ethical and liability issues, and possible conflicts of jurisdictions between
      countries involved.

PMID- 15455308
TI  - Development and testing of a novel biosynthesized XCell for treating chronic
      wounds.
AB  - Biosynthesized cellulose is produced by the bacteria, Acetobacter xylinum, and
      possesses unique properties not present in other biomaterials. The material is
      formed during fermentation having a multi-layered structure composed of fine,
      nonwoven, cellulose hydrophilic fibers. This structure allows biosynthesized
      cellulose to have a high-fluid capacity, superior strength, and biocompatibility,
      which makes it suitable for topical and implantable biomedical applications.
      Initial product development of biosynthesized cellulose has focused on advanced
      wound-care applications. The product, XCell (Xylos Corporation, Langhorne, PA,
      USA), has been bioengineered to have the ability to both donate and absorb
      moisture, depending on the wound environment. Comparative bench testing has shown
      that XCell is the only wound dressing with this unique dual-fluid-handling
      capability. The product has been studied thoroughly using animal models and
      proved to be safe and biocompatible. Human clinical testing has demonstrated its
      effectiveness in providing a moist environment, essential to treating hard-to
      heal chronic wounds. The major clinical benefits of the product include: 1) help
      in removal of non-viable tissue and promotion of autolytic debridement, which
      results in increased granulation tissue; 2) cleansing of wound margins that leads
      to epithelial migration and reduction of wound size; and 3) healing of various
      types of chronic wounds.

PMID- 15455309
TI  - Impact of microscopic foreign debris on post-surgical complications.
AB  - Minute pieces of debris left in the surgical site can interfere with optimal
      wound healing. Even when these microbodies are not obvious without magnification,
      their presence can cause post-surgical complications including infections,
      amplified and prolonged inflammation, permanent tissue damage, exaggerated and
      reduced quality scarring, granulomas, adhesions, organ dysfunction, infertility,
      and other pathological consequences. This chapter reviews foreign debris
      initiated, post-surgical complications; presents associated pathological
      mechanisms; identifies sources of debris contamination; describes foreign
      microbody characteristics that can further amplify pathological responses; and
      presents recommendations for minimizing their presence.

PMID- 15455310
TI  - Radiolabeled peptides: overcoming the challenges of post-surgical patient
      management of venous thromboembolism.
AB  - The serious clinical and economic impact of venous thromboembolic (VTE) disease
      is undisputed. What concerns practitioners and researchers alike is the seeming
      inability to truly mitigate the ramification of VTE, especially in the post
      surgical or postoperative subpopulation, in whom the risk of VTE is
      disproportionately high and often asymptomatic. Ironically, current approaches to
      the diagnostic evaluation of suspected VTE patients tend to favor the application
      of anatomic modalities, either invasive or technically challenging (eg,
      venography) or the performance of which is clinically inadequate (eg,
      ultrasonography) for post-surgical/postoperative patients. These modalities'
      primary principle of detection rely on the effects or results of an intricate
      pathophysiologic process, seemingly ignoring the critical role and potentially
      better prognostic value of endogenous hemostatic mechanisms. In other words, are
      we using the correct tools to seek the appropriate types of information in
      patients with suspected VTE? Research in nuclear medicine techniques for
      detecting VTE began approximately 25 years ago. Recently, the emergence of
      radiolabeled peptides as a clinically applicable technology platform has
      encouraged a different approach to evaluating VTE. Many radiolabeled peptide
      candidates are undergoing preclinical and clinical research. Currently,only one,
      99'Tc-apcitide (AcuTect), has been approved (since 1998) for clinical use in the
      United States. The growing numbers of physicians with experience using 9mTc
      apcitide (including those who remember using "'In-fibrinogen) has fueled ongoing
      clinical research to further elucidate the benefits of this unique peptide
      technology. Consequently, significant insight has been gained from large
      prospective clinical tri-als, of which one was conducted to support the approval
      of 99mTc-apcitide in Europe. Furthermore, this insight has kindled increasing
      interest in 99'Tc-apcitide and potential new entrants into this special "
      diagnostic class" (ie, radiolabeled peptides). Unlike the more popular anatomic
      modalities, radiolabeled pep-tides circumvent many of the clinical and anatomic
      challenges to objectively and accurately diagnose VTE. The importance of an
      objective and accurate diagnosis is understood, because it is paramount to a cost
      effective treatment strategy. In addition to describing the current activities
      concerning the development and use of radiolabeled peptides for clinical
      practice, this manuscript is intended to promulgate a thought-provoking argument
      for changing our current approach to the diagnostic evaluation of VTE,which also
      may transcend the post-surgical/postoperative subpopulation.

PMID- 15455311
TI  - Telesurgery versus telemedicine in surgery--an overview.
AB  - Telemedicine, the use of telecommunications technologies to deliver health
      services over a distance, is emerging as an innovative tool for the field of
      surgery. Recent feasibility and demonstration projects have documented the
      potential of telesurgery, the performance of a surgical intervention by a surgeon
      not physically located with the patient. However, the use of telemedicine for
      surgical services expands beyond telepresence surgery to include telementoring,
      teleproctoring, teleconferencing, and teleconsulting. This chapter overviews the
      current status of telemedicine applications across the full range of surgical
      care, which include training, preoperative, operative, and postoperative follow
      up. Although telesurgery garners the most attention, the paper concludes with the
      argument that the actual mainstay for telesurgery is the telemedicine components
      offered in the continuum of surgical services.

PMID- 15455312
TI  - Robot-assisted minimally invasive surgery: the importance of human factors
      analysis and design.
AB  - Success in robotic minimally invasive surgery (MIS) has been limited despite the
      innovations in robotic technology for surgical applications. Human factors
      engineering approach to the design and implementation of this technology is major
      to improving system performance and patient safety. The engineering discipline of
      human factors involves the study of factors and development of tools that enable
      human interaction with systems in a safe and effective manner. Human factors
      contribution is important to the product design life cycle, as it supports the
      design of a product capable of supporting, extending, and transforming user work
      in a cost-effective and timely fashion. A framework for modelling the interaction
      between the surgeon and technology in MIS is presented. This approach allows for
      identification of requirements and constraints at the physical, functional, and
      cognitive levels, which in turn guides the design of the technology and its
      interface. The human factors approach is expected to increase the effectiveness
      of the technology when deployed.

PMID- 15455313
TI  - Hand-assisted laparoscopic (HAL) gastric partition with roux-en-Y intestinal
      bypass.
AB  - The surgical treatment of obesity with proximal gastric partition and Roux-en-Y
      intestinal bypass is recognized as effective in producing meaningful weight loss
      of excess body weight. Pure laparoscopic surgery has been perfected by a small
      number of surgeons in the United States. To acquire this new skill requires
      extensive training and supervision. In the hands of inexperienced operators, it
      is associated with prolonged surgery times and significant complications. Hand
      assisted laparoscopic (HAL) surgery has been developed as an alternative method
      of minimally invasive surgery that can increase the number of surgeons who can
      offer laparoscopic surgery to their obese patients while decreasing the case load
      necessary to obtain expertise. The technique and approach of HAL surgery is
      presented in detail.

PMID- 15455314
TI  - Gastric banding for clinically severe obesity: results with the Swedish band.
AB  - Parallel with the rise of the obesity pandemic, bariatric surgery is quickly
      becoming one of the most frequently performed GI procedures. In selected, well
      informed patients, restrictive surgery offers a good alternative to more complex
      malabsorption-inducing procedures. Laparoscopic gastric banding is a reversible,
      technically straightforward procedure. Both early and late complications seen
      with the original models are less common with the Swedish adjustable gastric band
      SAGB (Ethicon Endosurgery, Johnson & Johnson, Dilbeek, Belgium) engineered as a
      low-pressure device. This chapter is a review of our experience with the SAGB and
      provides an overview of current controversies regarding its place in management
      of severe obesity.

PMID- 15455315
TI  - Laparoscopic Roux-en-Y gastric bypass vs. laparoscopic adjustable gastric banding
      for treatment of morbid obesity.
AB  - Bariatric surgery is a rapidly growing discipline in General Surgery. Roux-en-Y
      gastric bypass (GBP) is currently the most commonly performed bariatric surgical
      procedure for treatment of morbid obesity in the United States (U.S). The
      laparoscopic approach to (GBP) has led to a greater acceptance for surgical
      treatment of morbid obesity by the public and, in return, more surgeons are
      becoming interested in learning laparoscopic bariatric surgery to meet the high
      demand. Laparoscopic adjustable silicone gastric banding was approved in the U.S.
      by the Food and Drug Administration (FDA) for clinical use in 2001, and is
      emerging as an alternative laparoscopic option in management of morbid obesity.
      This chapter reviews the indications, techniques, and outcomes of laparoscopic
      GBP vs. laparoscopic adjustable gastric banding. The advantages and disadvantages
      of laparoscopic adjustable gastric banding compared to laparoscopic GBP is
      discussed.

PMID- 15455316
TI  - A new technique for laparoscopic hernia repair using fibrin sealant.
AB  - The purpose of this study was to evaluate whether an adequate prosthetic mesh
      fixation in laparoscopic preperitoneal inguinal hernia repair can be achieved
      with fibrin sealant (FS) (Tisseel trade mark, Hyland/Immuno Div., Baxter
      Healthcare Corp., Deerfield, IL, USA), and compare it with stapled fixation. The
      use of staples for prosthetic mesh fixation in laparoscopic preperitoneal hernia
      repair is associated with a small but significant number of complications, mainly
      nerve injury and hematomas. An alternative method of fixation should be as
      efficient as staples in preventing graft migration. An experimental study was
      conducted using swine models to compare the efficacy of polypropylene mesh
      fixation with FS to that achieved with staples and to non-fixed mesh grafts in
      the preperitoneal groin area. Twenty-five female pigs were used in the study. In
      each pig, a prosthetic mesh was placed laparoscopically in the groin area
      bilaterally and fixed with either FS, staples, or left without fixation. The pigs
      were killed after 12 days. The following outcome measures were evaluated:
      macroscopic findings including graft alignment and motion, tensile strength
      between the grafts and surrounding tissues, and histologic findings (fibrous
      reaction and inflammatory response). The procedures were completed
      laparoscopically in 49 sites. FS was used to fix 18 grafts; 16 with staples, and
      15 were not fixed. No significant difference was noted in graft motion between
      the FS and staple groups. The non-fixed grafts had a median motion of 5 mm
      (range: 0 to 10 mm), significantly more than the FS fixed (p<0.01) and stapled
      grafts (p<0.001). No significant difference was noted in median tensile strength
      between the FS and staples groups (0.955 Kg vs. 1.03 Kg, respectively) compared
      with 0.46 Kg in the non-fixed group (p<0.01). FS triggered a significantly
      stronger fibrous reaction and inflammatory response than those observed in the
      staples and control groups. An adequate mesh fixation in the extraperitoneal
      inguinal area can be accomplished using FS, based on our experimental evidence.
      The FS is equivalent to fixation achieved by staples and superior to no fixation.
      Soft fixation with FS prevents graft migration and avoids complications
      associated with use of staples.

PMID- 15455317
TI  - Rutkow PerFix-plug repair for primary and recurrent inguinal hernias--a
      prospective study.
AB  - Surgery of the groin hernia has become more a question of the applied tension
      free, mesh technique. Whereas studies on laparascopic versus open tension-free
      hernia repair or open-mesh versus open-nonmesh repair have been performed
      sufficiently, data regarding the open tension-free plug-and-patch technique are
      rather poor. During the period from January 2001 to October 2003, we followed and
      filed 766 hernia repairs in the plug-and-patch technique of Rutkow. Follow up was
      during the hospital stay, 4 weeks, and minimally 12 months after operation. The
      main follow-up variables were complications, recurrence rate, and pain. The mean
      operating time was 37.8 +/- 15.85 (12-135) minutes. In 141 (19.3%) patients
      (n=730), the ilioinguinal nerve was resected. The 1 intraoperative complication
      that occurred was a severed small intestine. Length of hospital stay was 2.09 +/-
      1.35 (0-17) days, work leave lasted for 15.3 +/- 12.42 (0-60) days, and return to
      normal daily activities was possible within 6.54 +/- 6.86 (0-35) days. Twenty-two
      (2.9%) patients (n=766) developed a postoperative hematoma as the most common
      complication, and a reoperation was required 17 (2.2%) times during the hospital
      stay. Early complications included hematoma (3.7%), seroma (3.5%), infection
      (0.2%), necrosis of 1 testicle (0.2%), persisting scrotal swelling (1.5%),
      persisting pain (0.9%), and hypoesthesia (2.4%). Within 4 weeks, 4 (0.9%)
      patients were reoperated for 1 seroma, hematoma, infection, and testicle
      necrosis. After 605.4 +/- 154.5 (365-1018) days, the following 19 (5.7%) patient
      complaints were noted: persisting pain (2.1%), hypoesthesia (1.8%), foreign-body
      feeling (0.6%), scrotal swelling (0.6%), and 1 (0.3%) mesh dislocation. Six
      (1.8%) reoperations have been performed. The overall recurrence rate was 1.8%
      (n=6), for primary 1.5% (n=4), and 3.3% (n=2) for recurrent hernias; 96.3% of the
      patients would agree to undergo the same operation a second time. Tension-free
      repair of the inguinal hernia by the plug-and-patch technique is a quick and
      secure method that simplifies hernia surgery without compromising the high
      quality standards such as a low recurrence rate and low pain load of the patient.
      Patients had a fast recovery with a subsequent short work leave. The method is a
      simple, effective, and economical operation, suitable as a standard performed in
      local anesthesia on an out-patient basis.

PMID- 15455318
TI  - Risk of gas embolism in hand-assisted versus total laparoscopic hepatic
      resection.
AB  - Laparoscopic hepatic resection represents an alternative to open surgery in
      patients with advanced underlying hepatic disease. Management of haemorrhage and
      the risk of gas embolism are the major problems in laparoscopic liver surgery. In
      this study, safety and efficacy of liver dissection using ultrasonic energy was
      investigated in hand-assisted versus total laparoscopic surgery. The study had a
      special emphasis on evaluating the risk of gas embolism during both procedures.
      Female pigs were divided into two groups for A) total laparoscopic (n=7), and B)
      hand-assisted laparoscopic (n=7) hepatic resection. For tissue dissection, an
      ultrasound aspirator (CUSA) was used in both groups. Laparoscopic procedure was
      performed under a CO2 pneumoperitoneum (intraperitoneal pressure: 12 mmHg).
      Before dissection, a Pringle manoeuver was carried out. The anaesthetized pigs
      were monitored haemodynamically by an arterial line and Swan-Ganz catheter.
      Transoesophageal echocardiography (TEE) was performed with special attention to
      the right atrium and ventricle. Gas emboli were graded according to size and
      correlated with haemodynamic and blood-gas data. In both groups, the ultrasound
      aspirator enabled an effective tissue dissection. In total laparoscopic hepatic
      resection, TEE monitoring disclosed gas embolism in 5/7 (71%) animals. In 3/7
      (42%) animals, gas embolism was accompanied by a sequence of cardiac arrhythmia.
      No direct correlation was noted between episodes of embolism and blood-gas
      variables. None of the pigs died after episodes of embolization. In hand-assisted
      liver resection, no air embolism was noted. The internal hand impressively
      facilitated organ exposure and provided an immediate and efficient haemorrhage
      control. The use of an ultrasound aspirator system enables an effective
      laparoscopic hepatic dissection. Total laparoscopic liver dissection is at
      increased risk for gas embolism, whereas hand-assisted laparoscopic procedure
      appears to reduce this risk. Due to tactile response and facilitated retraction
      of the liver parenchyma, the hand-assisted procedure shows impressive advantages
      in laparoscopic liver surgery.

PMID- 15455319
TI  - Intraoperative ultrasonography in patients who undergo liver resection or
      transplantation for hepatocellular carcinoma.
AB  - Careful staging of hepatic tumors forms the basis of appropriate selection of,
      and is a precondition for, customized treatment. Advances in radiodiagnostic
      technology have increased the sensitivity of noninvasive liver staging by means
      of magnetic resonance imaging (MRI), computed tomography (CT), and helical CT
      (HCT). Nevertheless, surgical exploration and intraoperative ultrasonography
      (IOUS) are considered the "gold standard." The value of HCT and IOUS was
      investigated in patients who underwent orthotopic liver transplantation (OLT)
      (group A; n=23) or hepatic resection for hepatocellular carcinoma (HCC) (group B;
      n=52). In group A, the results of liver imaging (HCT performed immediately before
      OLT, IOUS) were compared with histopathological results after 3-mm slicing of the
      explanted liver. In group B, patients were evaluated by CT (n=8), HCT (n=43), MRI
      (n=18), or both, as indicated by the respective surgeon. The results were
      compared with those of surgical exploration and IOUS (n=52), as well as with the
      pathological examination of the resected liver specimen. In group A, 52 malignant
      lesions were detected by histopathology. By each of the preoperative examinations
      (IOUS, HCT), 54 lesions were suspected of being malignant. Thirteen HCCs were
      missed by HCT (for IOUS: n=4) and 15 lesions were false-positive (for IOUS: n=6).
      Thirty-nine of 52 lesions were verified to be true-positive by HCT in contrast to
      48/52 by IOUS, which resulted in sensitivities of 75% (HCT) and 92% (IOUS,
      P=0.017), respectively. In group B, the sensitivity of CT was 77%, HCT 90%, MR
      93%, and IOUS 99% (P<0.01). In 10%, the strategy of surgical treatment was
      changed because of IOUS findings. IOUS offered relevant additional information in
      6%. Even after sufficient preoperative evaluation, IOUS can provide additional
      information that frequently has a remarkable impact on surgical decision-making.
      Identification of HCC is commonly hampered by coexistent cirrhosis.
      Identification of lesions and orientation of borders to non-tumorous tissue are
      assessed reliably by IOUS. Thus, IOUS remains a mandatory tool in patients
      treated by locoregional surgical modalities such as resection, cryotherapy, and
      intraoperative ethanol instillation for HCC even after refinement of radiological
      technologies.

PMID- 15455320
TI  - Complications and sequelae of thyroidectomy and an analysis of surgeon experience
      and outcome.
AB  - Theodor Kocher is credited with refining the technique of thyroidectomy and
      reducing the incidence of postoperative hemorrhage. He also recognized the
      importance of preservation of the parathyroid glands. His accomplishments led to
      a reduction in surgical mortality, from 50% to less than 4.5%. Additional
      improvements in technique have reduced the mortality rate to near zero.
      Morbidity, however, remains a concern for surgeons who perform thyroid surgery.
      Complications and sequelae of thyroid surgery are reviewed, including recurrent
      and superior laryngeal nerve injury, temporary hypocalcemia, permanent
      hypoparathyroidism, thyroid storm, bleeding, wound infection, and hypothyroidism.
      The association between the volume of thyroidectomies performed by a surgeon and
      outcome is also discussed in this chapter.

PMID- 15455321
TI  - New endometrial ablation techniques for treatment of menorrhagia.
AB  - Endometrial ablation is an excellent alternative to hysterectomy in women with
      menorrhagia and small intramural fibroids. Preoperative evaluation, which
      includes office hysteroscopy or saline infusion sonography, is critical to
      patient management and choice of procedure. A vast array of endometrial ablation
      technology is available currently that includes balloon therapy, cryosurgery hot
      circulating saline, bipolar impedance technology, and microwave: (1) ThermaChoice
      UTB System (Gynecare, Inc., Somerville, NJ, USA), (2) Uterine Balloon Therapy
      (UBT) System, HerOption Uterine Cryoblation Therapy System (American Medical
      Systems, Inc., Minnetonka, MN, USA), (3) Hydro ThermAblator HTA System (BEI
      Medical/Boston Scientific, Natick, MA), (4) NovaSure System (Novacept, Palo Alto,
      CA, USA), and (5) Microsulis Microwave Endometrial Ablation (MEA) System
      (Microsulis Medical Ltd., Pompano Beach, FL, USA). Each method is described
      herein, and Summary of Safety and Effectiveness Data (SSED) data for each product
      are reviewed.

PMID- 15455322
TI  - Latest advances in TVT tension-free support for urinary incontinence.
AB  - The Tension-free Vaginal Tape (TVT) procedure is the first of a new generation of
      minimally invasive operations for treatment of female urinary stress
      incontinence. A new theory of the cause of stress incontinence, the "Mid-urethra
      Theory," was the basis for development of the TVT operation. Systematic,
      prospective clinical trials have proved the TVT procedure is effective and safe
      in curing stress incontinence. Assessed by strict objective and subjective
      outcome measures, cure rates of 85% were reported, with another 5%-10% being
      improved significantly. The method is equally effective in groups of patients
      with uncomplicated genuine stress incontinence, recurrent incontinence, mixed
      incontinence, and those with intrinsic sphincter deficiency. Careful prospective
      registering of complications associated with the procedure indicate complication
      rates are low when proper training is provided and the operation is performed in
      its standardized method. Five years of follow up show a cure rate of 85%, which
      indicates little decline in cure rates by time. Preliminary analysis of seven
      year results shows a cure rate of 81%.

PMID- 15455323
TI  - Endometriosis: insights into its pathogenesis and treatment.
AB  - Clinical and basic science research in endometriosis has been severely hampered
      by the lack of accurate noninvasive diagnostic tools. The advent of powerful
      genomic and proteomic technology may help elucidate the etiology and
      pathophysiology of this complex and enigmatic disease and open new avenues for
      diagnosis and treatment. Genomic techniques have demonstrated that certain gene
      products are abnormally expressed in endometriotic tissues.

PMID- 15455324
TI  - Robot-assisted sutureless minimally invasive mitral valve repair.
AB  - Our institution has performed over 100 robot-assisted mitral valve repairs. The
      procedure has shown many advantages to conventional sternotomy-based repair.
      However, the robotic approach leads to longer cross-clamp and bypass times than
      conventional sternotomy. As a result of the increased risk of myocardial damage
      and arrhythmias from lengthy arrest times, nitinol U-clips have been used in the
      laboratory and currently in patients for the tissue-annuloplasty ring
      approximation. The technology replaces the time-consuming task of knot tying, as
      well as provides better visualization during placement of the annuloplasty ring.
      The animal studies show excellent tissue incorporation. Short-term
      echocardiographic imaging shows durability without evidence of mitral stenosis or
      regurgitation. Further studies are ongoing in our patient population, and the
      data suggest shorter, more efficient and effective robot-assisted mitral valve
      repairs.

PMID- 15455325
TI  - Stent graft treatment of thoracic aortic disease.
AB  - This study was a retrospective analysis of both the efficacy and long-term
      outcome of endovascular management of thoracic aortic disease. From March 1999 to
      August 2003, 129 patients (110 males; 19 females) were enrolled. They were
      divided into four groups: aneurysms (41, 5 of which acutely ruptured, Group A),
      post-traumatic lesions (24, 14 acute and 10 chronic, Group B) and complicated
      type B dissections (42, 23 acute and 19 chronic, Group C). Twenty-two of the 129
      patients with chronic type B dissection, not suitable for endovascular treatment,
      received medical management only (Group D). All patients underwent computed
      tomography (CT) scan and angiography as preoperative assessment. Stent-graft
      systems were Talent -Medtronic, Excluder-Gore, Zenith-Cook and Endofit-Endomed,
      deployed by transesophageal echocardiography (TEE) monitoring. An optimal
      deployment with sealing of the graft was achieved in 95.3% (102/107) of the
      treated patients discharged in good condition within 6 days. Five patients (3 in
      Group A and 2 in Group C) underwent endovascular completion of the elephant trunk
      technique successfully. In 5 patients affected by atherosclerotic aneurysm, in a
      single-time procedure, we have also treated the abdominal aortic aneurysm by
      endovascular. No spinal cord injuries were observed. The follow up (average:
      20.82+/-10.01 months), performed with serial chest CT scans, was 100% complete.
      No stent-graft related complications were detected. In 2 patients with chronic
      dissection, an asymptomatic type II endoleak was detected. A total of 4 hospital
      deaths resulted in an overall operative mortality rate of 3.7%. Seven patients
      (6.5%) died during the follow-up period, whereas a 31.8% (7/22) mortality rate
      (p<0.001) was observed within the medical treatment group. Endovascular treatment
      of thoracic aortic diseases, even in the acute phase, may represent a valid
      option, especially when compared to medical therapy.

PMID- 15455326
TI  - Bentall procedures with a novel valved conduit incorporating "sinuses of
      Valsalva".
AB  - The Bentall operation is preferred when a diseased aortic valve is associated
      with a dilated or dissected ascending aorta. Composite valved grafts have been
      devised to facilitate and expedite this procedure. The initial clinical results
      of the Bentall procedure using a vascular conduit modified to incorporate
      "pseudosinuses of Valsalva," with the aim of simplifying coronary button
      anastomoses and decreasing tension upon them, is described herein. Over a period
      of 40 months since its introduction, the novel conduit has been used, for a
      Bentall procedure in 37 consecutive patients. Of this group, 31 were men and 6
      were women, with a mean age of 63.8+/-9.9 years. Five were Marfan patients, 8
      were patients after acute or chronic dissection, and 8 were patients who required
      redo procedures. In 22 patients, the modified conduit was used in association
      with a biological valve (4 stentless valve) and in 15, with a mechanical valve.
      The mean durations of CPB and X-clamp time were 117+/-32 and 88+/-22 minutes,
      respectively. No operative or late deaths occurred after a mean follow-up period
      of 20+/-12 months. This study indicates that the new vascular prosthesis appears
      to facilitate implantation by maintaining a more natural shape of the
      reconstructed aortic root.

PMID- 15455327
TI  - Distal revascularization-interval ligation (DRIL) procedure for ischemic steal
      syndrome (ISS) after arteriovenous fistula placement.
AB  - Ischemic steal syndrome (ISS) is an uncommon complication of arteriovenous (AV)
      access placement. Distal revascularization interval ligation (DRIL) is an
      alternative to preserve AV access and resolve ISS simultaneously. This case
      illustrates the problem of ISS and tissue loss, and its successful treatment
      after undergoing the DRIL procedure. Other options for management of ISS also are
      reviewed.

PMID- 15455328
TI  - Computer-assisted surgery in total knee arthroplasty:recent advances.
AB  - Computer-assisted surgery (CAS) for total knee replacement was first approved for
      use in the U.S. in 2001. Since its introduction, however, there has been a rapid
      expansion of this technology and several different types of navigation systems
      have been developed by several different manufacturers. Each new version of the
      software has incorporated increasingly sophisticated analysis modules to allow
      not only accurate alignment of the limb and component position, but also to
      assess ligament balance and knee kinematics. The purpose of this chapter is to
      review the basic elements of CAS, the author's clinical experience, and
      improvements currently being developed with this technology.

PMID- 15455329
TI  - Hybrid stem fixation in revision total knee arthroplasty (TKA).
AB  - The purpose of this study was to retrospectively compare the clinical and
      radiographic results of the Maxim Posterior Stabilized Constrained (PCS) (Biomet
      Orthopaedics, Inc., Warsaw, IN, USA) knee system using the hybrid fixation versus
      the fully cemented fixation of stems of the same length. The cohort in this study
      included 115 knees in 104 patients, with a minimum 2-year follow up
      postoperatively. All patients were evaluated with the Knee Society clinical
      rating score and roentgenographic evaluation. Of the 115 revision total knee
      arthroplasty (TKA) cases, the hybrid-fixation technique was used on both the
      femoral and tibial components of 75 (Group I-hybrid femur, hybrid tibia); the
      fully cemented technique was used on both components of 24 (Group II-cemented
      femur, cemented tibia); the hybrid-fixation technique was used on the femoral
      component and full cement on the tibial component of 13 (Group III-hybrid femur,
      cemented tibia); the femoral component was fully cemented, and tibial component
      had the hybrid-fixation technique used on 3 (Group IV-cemented femur, hybrid
      tibia). The average follow up was 44 (range: 24-126) months. At the most recent
      evaluation, the Knee Society score improved from an average preoperative value of
      51.7 to 76.7, the pain score improved from 14.0 to 33.3, and the functional score
      improved from 40.5 to 47.0. The average stem-to-canal fill ratio was 80% in the
      femur and 85% in the tibia (p<0.05). Stem-to-canal fill ratio did not appear to
      influence clinical outcome. Radiolucent lines less than 2 cm were observed more
      frequently in the hybrid-cemented stems (89%) than the fully cemented stems (58%)
      at an average 8-year follow up postoperatively (p<0.05). A lower, but not
      statistically significant, failure rate was observed in the hybrid group in
      comparison with the cemented group.

PMID- 15455330
TI  - Medial gastrocnemius flap for reconstruction of knee extensor mechanism
      disruption after total knee replacement (TKR).
AB  - This chapter describes a technique for reconstruction of the knee extensor
      mechanism disruption after total knee replacement (TKR). Disruption of the knee
      extensor mechanism is an infrequent but serious complication. The options for
      treatment include observation, bracing, fixation with sutures or staples,
      autologous-tissue augmentation with use of the semitendinosus or gracilis tendon,
      turndown of the quadriceps tendon and reconstruction with an intercalary
      allograft. These options have been associated with a high risk of complications
      and have not addressed the associated problems of contracted devascularized skin
      flaps or deficient patellar bone stock. The medial gastrocnemius flap has been
      shown to be suitable for providing soft-tissue coverage of the proximal aspect of
      the tibia, knee, and distal aspect of the femur. Historically the technique for
      reconstruction of the extensor mechanism was described for limb salvage after
      resection of proximal aspect of the tibia for malignant tumors. This described
      technique is an adaptation of such previously accepted techniques for disruption
      of the extensor mechanism after total knee arthroplasty (TKA). The use of a
      medial or an extended medial gastrocnemius flap appears to be a reliable option
      for reconstruction of a ruptured extensor mechanism after TKA.

PMID- 15455331
TI  - Patella baja and total knee arthroplasty (TKA): etiology, diagnosis, and
      management.
AB  - Patella baja, that can be divided into congenital, acquired, or a combination of
      the two, is commonly encountered in total knee arthroplasty (TKA). Congenital
      patella baja refers to a patella distal in relationship to the femoral trochlea
      and present since an early age. Acquired patella baja may occur secondary to
      distal positioning of the patella relative to the femoral trochlea or shortening
      of the patellar tendon, as a result of trauma or surgery. Patella baja also can
      occur postoperatively as a result of scarring and shortening of the patellar
      tendon, scarring of the patellar tendon to the anterior aspect of the tibia, or
      both. Another cause of acquired patella baja seen commonly in TKA is elevation of
      the joint line, referred to as pseudo-patella baja. The patella remains in a
      normal position relative to the femoral trochlea; however, the distance between
      the patella and tibia is narrowed. Pseudo-patella baja can be a result of tibial
      or femoral over-resection, which necessitates a large polyethylene insert.
      Alterations of the patello-tibial distance can occur during TKA by excessive soft
      tissue release that requires elevation of the joint to regain stability and
      placement of the patellar polyethylene component distally on the patella.
      Prevention is the easiest way to avoid potential problems with patella baja
      during TKA; however, the surgeon is often confronted with this situation during
      total knee revisions. Failure to address patella baja can lead to decreased range
      of motion (ROM), a decreased lever arm, extensor lag, impingement of the patella
      against the tibial polyethylene or tibial plate, anterior knee pain, increased
      energy expenditure, and rupture of the patellar or quadriceps tendons. Treatment
      of patella baja first depends on determining the cause and distinguishing between
      patella baja and pseudo-patella baja. Five different methods to measure patella
      baja are reviewed and include: (1) Blumensaat's line, (2) Insall-Salvati ratio,
      (3) Modified Insall-Salvati ratio, (4) Blackburne-Peel, and (5) Caton-Deschamps.
      Corrective measures include reestablishing the joint line by use of distal
      femoral augments, tibial tubercle osteotomy with proximal displacement,
      lengthening of the patellar tendon, shaving of the anterior portion of the tibial
      polyethylene, and placement of the patellar implant in a cephalad position.

PMID- 15455332
TI  - Endoscopic ACL reconstruction using stryker biosteon cross-pin femoral fixation
      and interlock cross-pin tibial fixation.
AB  - Hamstring tendon autografts have, over the past decade, increasingly become the
      graft of choice for anterior cruciate ligament (ACL) reconstructions. Studies
      have shown that multiply stranded hamstring grafts have superior biomechanical
      characteristics when compared to patellar tendon autografts. Harvests of
      hamstring tendons have been shown to cause less donor-site morbidity than the
      harvest of patellar bone-tendon-bone grafts. Historically, however, fixation
      methods for hamstring grafts have limited their successful use. Fixation for both
      the tibia and femur distant from the intra-articular portions of the graft
      decreased the stiffness of the construct. The fixation also contributed to tunnel
      widening and ganglion formation. New methods have been developed to maximize the
      mechanical strengths of hamstring grafts and optimize biological factors in
      healing of the graft to the bone tunnels. Femoral cross-pin fixation provides
      secure fixation close to the knee joint, while also allowing for placement of the
      graft in the native ACL footprint at the far posterior aspect of the
      intercondylar notch. Tibial interference screw fixation allows fixation close to
      the joint as well. Addition of the interlock pin through the interference screw
      increases pullout strength significantly. Recent advances in material science
      have led to the development of bioabsorbable implants that afford high initial
      fixation strengths while limiting subsequent complications from permanent
      hardware.

PMID- 15455333
TI  - Computer-navigated ACL reconstruction with the OrthoPilot.
AB  - Within the minimally invasive-operation techniques, small approaches are
      desirable in many fields of the surgery to reduce soft-tissue trauma; however,
      the risk exists that the surgeon will lose the general view of the topographic
      structures. The remedy lies in computer navigation with the OrthoPilot. This
      navigation system has already been used successfully for knee endoprosthesis. A
      special software was developed for use of the navigation-system, OrthoPilot, for
      ACL reconstruction. This system is capable of determining the exact optimum
      position of tunnel replacement by computer navigation. This determination is made
      by a high-precisive infra-red camera and rigid bodies fixed onto the patient. The
      experience gained in performing 150 ACL reconstructions to date demonstrates the
      ease of handling, reduction in extra operation time to a minimum of 10-15
      minutes, and only minimal trauma by fixing the rigid bodies. In all cases, an
      optimum position was documented for the tunnel replacement. Furthermore, no
      expensive pre-operation x-rays (CT scan, nuclear spin) are needed. Use of the
      computer-assisted navigation system demonstrated that femoral and tibial tunnel
      replacement can be positioned precisely. Thus, a false position of the tunnel
      replacement, the main cause of' transplant-failure, can be avoided. The
      OrthoPilot is an important support system for both less-experienced and
      experienced surgeons when performing surgical ACL revisions.

PMID- 15455334
TI  - Indications, methods, and results of cemented, hybrid, and cement-free
      implantation of THR.
AB  - THR has become one of the most widely performed operations in orthopaedic
      surgery. In Germany, more than 180,000 THRs are currently done annually with
      increasing tendency. We use four different types of endoprostheses: (1) cemented,
      (2) cement-less, (3) hybrid (cement-free implanted socket and cemented stem), and
      (4) hemi-endoprosthesis (cemented stem without socket). A total number of 600
      patients were included in a prospective follow-up study during 5 to 20 years,
      with a mean follow-up period of 10 years. The relevant question of whether to use
      a cemented, hybrid, or cement-free version of THR is, in our opinion, no longer a
      concern. All the methods have their advantages, disadvantages, indications, and
      contraindications. After the "Endler-era", significant differences are not noted
      between the groups of cemented, hybrid, and cement-less implants that impact on
      the clinical results and loosening rates.

PMID- 15455335
TI  - Navigated minimal invasive total hip arthroplasty.
AB  - All lines of development in Computer Aided Orthopaedic Surgery (CAOS) can be seen
      as critical steps in a broader effort to innovate the orthopaedic field. CAOS
      addresses the need to perfect implant placement and joint alignment. Minimally
      invasive techniques represent equally important new developments in the field of
      arthroplasty. It seems inevitable that these two fields converge. A navigation
      system for a minimally invasive approach to the hip would follow these primary
      design concepts: pure intraoperative system, planning included on plane X-rays,
      small trackers for acetabular and femoral navigation, control of leg-length
      change through implant placement as well as joint offset, kinematic test of range
      of motion (ROM).

PMID- 15455336
TI  - Advances in DVT prophylaxis and management in major orthopaedic surgery.
AB  - Every year, approximately 2 million people experience a deep venous thrombosis
      (DVT). Approximately 600,000 of these people are diagnosed with a pulmonary
      embolism and about 10% of these die. It has been established that surgery,
      anesthesia, and bed rest increase the risk of DVT, and therefore, patients who
      undergo a major lower-extremity procedure should receive prophylaxis. During the
      past 10 years, the choices of pharmacological and mechanical prophylaxis have
      increased greatly. Warfarin is probably the most widely used prophylactic method
      in the U.S., but low-molecular-weight heparin (LMWH) use has increased. Also
      available is a synthetic pentasaccharide that acts as an anti-Xa inhibitor to
      decrease DVT without increase in bleeding. All but warfarin are given by
      subcutaneous injection and require no laboratory management to adjust the
      medication. Another drug in clinical trials is a direct thrombin inhibitor taken
      orally in a fixed dose that does not require monitoring. Non-pharmacological
      prophylaxis and/or stacked modalities, although used, have not shown the efficacy
      of pharmacological prophylaxis. With the incidence of DVT reported in the range
      of 41% to 85% without prophylaxis in joint replacement and hip-fracture surgery,
      prophylaxis is warranted in all lower-extremity joint replacement and hip
      fracture patients.

PMID- 15455337
TI  - New concepts for bone fracture treatment and the Locking Compression Plate.
AB  - The operative treatment of bone fractures using plates and screws is a standard
      successful technique. Internal fixation with plates and screws leads to
      additional trauma and disturbance of the bone blood supply, which increases the
      risk of delayed union and infection. However, problems also are encountered in
      the fixation of osteoporotic bone. The locked internal fixator technique is an
      approach to optimize internal fixation. It aims at flexible elastic fixation to
      imitate spontaneous healing, including induction of callus formation. The
      technology supports what is currently called "minimally invasive plate
      osteosynthesis" (MIPO), which provides priority to biology over mechanics. An
      implant system called "Locking Compression Plate (LCP)" was developed, based on
      many years of experience with compression plating and good clinical results
      obtained with internal fixators, such as the Less Invasive Stabilization Systems
      (LISS). It combines the two treatment methods (ie, the compression plating and
      locked internal fixation methods) into one system. This chapter describes the
      basic principles of locked internal fixators and some clinical results with the
      LISS and LCP systems to illustrate the potential of these new systems.

PMID- 15455338
TI  - Viscosupplementation for treatment of osteoarthritis: from initial discovery to
      current status and results.
AB  - Viscosupplementation is a therapeutic modality based on the replacement of
      synovial fluid or exudates with an elastoviscous hyaluronan solution. The first
      clinical trials were carried out on race horses with painful osteoarthritis of
      traumatic origin. In the early 1970s, the clinical trials were extended to
      painful osteoarthritis in humans. Analgesic effects lasting longer than the
      residence time of the injected hyaluronan in joints were reported both in horses
      and humans. The hyaluronan used was a noninflammatory fraction of the molecule
      with an average molecular weight of 2-3 million at a 1% concentration. The
      analgesic effect of this elastoviscous hyaluronan solution was demonstrated in
      behavioral animal pain models. Later it was shown that the elastoviscous
      properties of hyaluronan solutions are the determining factors in reducing pain
      elicited nerve activity in both normal and inflamed cat and rat joints. It also
      was demonstrated in animal arthritis models that elastoviscous hyaluronan
      solutions promote the healing of traumatic intra-articular wounds. From the mid
      1980s, several hyaluronan preparations of greatly varying average molecular
      weight but with the same concentration were introduced as viscosupplementation
      based therapeutic agents. The elastoviscous properties of these solutions varied
      also, because of the greatly varying average molecular weights (0.5-6.0 million),
      imitating the rheological properties of either healthy or pathological synovial
      fluid. Currently, viscosupplementation products available worldwide vary greatly
      in their elastoviscous properties, and their dosage is not standardized in terms
      of frequency of injections required or in regard to the removal of exudates
      before injection. The question of which patient at what stage of the disease
      responds best with long-lasting pain relief to the many therapeutic products
      marketed with greatly varying elastoviscous properties has not yet been answered.
      At the same time, viscosupplementation was introduced, the same highly
      elastoviscous hyaluronan solutions also were applied in ophthalmic surgery as
      viscosurgical tools to protect sensitive tissues in the eye during surgery and to
      be used as soft instruments for tissue manipulation. Modified hyaluronan products
      (gels) also were introduced for augmentation of the intercellular matrix in
      tissues (viscoaugmentation) and for separating tissues to prevent adhesions and
      excessive scar formation (viscoseparation). Hyaluronan and its derivatives (gels)
      also have been used for drug delivery. The therapeutic use of highly
      elastoviscous solutions and gels of hyaluronan and its derivatives to build
      intercellular matrices for supplementation, regeneration, and developing new
      tissues introduced the concept of matrix engineering into medical practice.

PMID- 15455339
TI  - Hemi and total TMJ reconstruction using the Christensen prostheses: a
      retrospective and prospective evaluation.
AB  - This chapter further affirms the safety and efficacy of hemi and total
      temporomandibular joint (TMJ) reconstruction with the Christensen TMJ Prostheses
      (TMJ Implants, Inc., Golden, CO, USA). Hemi and total TMJ reconstruction with the
      Christensen TMJ prostheses was first introduced by Robert W. Christensen, DDS in
      1961 and 1965, respectively, and is gaining widespread acceptance as a viable
      alternative in the treatment of temporomandibular joint disorders (TMD). The
      Christensen TMJ devices have been used to treat various disorders in large
      numbers of patients, and the pertinent results of 10 years of study are reported
      in this chapter.

PMID- 15455340
TI  - Absence of EGFR mutation in the kinase domain in common human cancers besides non
      small cell lung cancer.

PMID- 15455341
TI  - Anthocyanin- and hydrolyzable tannin-rich pomegranate fruit extract modulates
      MAPK and NF-kappaB pathways and inhibits skin tumorigenesis in CD-1 mice.
AB  - Chemoprevention has come of age as an effective cancer control modality; however,
      the search for novel agent(s) for the armamentarium of cancer chemoprevention
      continues. We argue that agents capable of intervening at more than one critical
      pathway in the carcinogenesis process will have greater advantage over other
      single-target agents. Pomegranate fruit extract (PFE) derived from the tree
      Punica granatum possesses strong antioxidant and antiinflammatory properties.
      Pomegranate fruit was extracted with acetone and analyzed based on matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry and found
      to contain anthocyanins, ellagitannins and hydrolyzable tannins. We evaluated
      whether PFE possesses antitumor-promoting effects. We first determined the effect
      of topical application of PFE to CD-1 mice against 12-O-tetradecanoylphorbol-13
      acetate (TPA)-induced conventional markers and other novel markers of skin tumor
      promotion. We found that topical application of PFE (2 mg/mouse) 30 min prior to
      TPA (3.2 nmole/mouse) application on mouse skin afforded significant inhibition,
      in a time-dependent manner, against TPA-mediated increase in skin edema and
      hyperplasia, epidermal ornithine decarboxylase (ODC) activity and protein
      expression of ODC and cyclooxygenase-2. We also found that topical application of
      PFE resulted in inhibition of TPA-induced phosphorylation of ERK1/2, p38 and
      JNK1/2, as well as activation of NF-kappaB and IKKalpha and phosphorylation and
      degradation of IkappaBalpha. We next assessed the effect of skin application of
      PFE on TPA-induced skin tumor promotion in 7,12-dimethylbenz(a)anthracene
      initiated CD-1 mouse. The animals pretreated with PFE showed substantially
      reduced tumor incidence and lower tumor body burden when assessed as total number
      of tumors per group, percent of mice with tumors and number of tumors per animal
      as compared to animals that did not receive PFE. In TPA-treated group, 100% of
      the mice developed tumors at 16 weeks on test, whereas at this time in PFE
      treated group, only 30% mice exhibited tumors. Skin application of PFE prior to
      TPA application also resulted in a significant delay in latency period from 9 to
      14 weeks and afforded protection when tumor data were considered in terms of
      tumor incidence and tumor multiplicity. The results of our study provide clear
      evidence that PFE possesses antiskin-tumor-promoting effects in CD-1 mouse.
      Because PFE is capable of inhibiting conventional as well as novel biomarkers of
      TPA-induced tumor promotion, it may possess chemopreventive activity in a wide
      range of tumor models. Thus, an in-depth study to define active agent(s) in PFE
      capable of affording antitumor-promoting effect is warranted.

PMID- 15455342
TI  - Mononucleotide repeats BAT-26 and BAT-25 accurately detect MSI-H tumors and
      predict tumor content: implications for population screening.
AB  - Tumors with a defective DNA mismatch repair system (MSI-H tumors) have distinct
      molecular and clinicopathologic profiles compared with mismatch repair-proficient
      tumors and are associated with a relatively favorable prognosis. There is
      evidence to suggest that colorectal cancer patients with MSI-H tumors respond
      differently to adjuvant chemotherapy. Determination of MSI status also has
      clinical application for assisting in the diagnosis of suspected hereditary
      nonpolyposis colorectal cancer cases. For these reasons, it is becoming
      increasingly apparent that testing for MSI should be conducted routinely in human
      cancer types that frequently present with such a phenotype. BAT-26 and BAT-25 are
      mononucleotide repeats that are widely used to establish the MSI status of human
      tumors. We show here that their allelic size profiles provide an estimate of the
      percentage of contaminating normal cells in MSI-H tumors. These markers are
      sensitive enough to detect instability when the tumor cell content of a sample is
      as low as 5-10%. MSI-H tumors contain mutations in coding repeats within genes
      known to be targets for instability. In cases with low tumor cell content, no
      mutations in any of 9 coding repeats were detected. However, when these samples
      were enriched for tumor cells, mutations were detected in the same target genes.
      Thus, BAT-26 and BAT-25 markers accurately identify MSI-H tumors without prior
      need for enrichment for tumor cells and indicate which samples require further
      purification before screening for mutations in target genes for instability. Our
      results have implications for large-scale screening of cancer patients to
      determine MSI-H status and prognosis.

PMID- 15455343
TI  - Platelet-activating factor and liver metastasis of colorectal cancer.

PMID- 15455344
TI  - JTE-522, a selective cyclooxygenase-2 inhibitor, inhibits induction but not
      growth and invasion of 1,2-dimethylhydrazine-induced tubular adenocarcinomas of
      colon in rats.
AB  - We have previously demonstrated that JTE-522, a selective cyclooxygenase-2 (COX
      2) inhibitor, inhibited development of aberrant crypt foci (ACF) in rats, a
      putative preneoplastic lesion in colon, and suggested its inhibitory potential in
      rat colon carcinogenesis. To evaluate the chemopreventive properties of JTE-522,
      the present study was design to evaluate the inhibitory effects of JTE-522 on rat
      colon tumorigenesis induced by 1,2-dimethylhydrazine (DMH). Rats at 6 weeks of
      age were divided into 4 groups. One week after the start of the experiment, all
      rats received DMH by s.c. injection at a dose of 40 mg/kg body weight once a week
      for 4 successive weeks. As the initiation and postinitiation treatment groups,
      groups 1-3 were fed diets containing 0, 50, or 150 ppm JTE-522, respectively,
      from the start of the study to the end. As the postinitiation treatment group,
      group 4 was given 150 ppm JTE-522 from 1 week after the last DMH injection to the
      end of the study. Forty weeks after the start of the experiment, administration
      of 150 ppm JTE-522 during both initiation and postinitiation stages significantly
      inhibited the incidences of tubular adenocarcinomas and total carcinomas, as well
      as total tumors in the colon. The inhibitory effect of JTE-522 was most prominent
      for tubular adenocarcinomas, but was not observed in the nontubular carcinomas
      (signet-ring cell and mucinous carcinomas). Almost equal inhibitory effects on
      tubular adenocarcinomas were also observed in the rats given 150 ppm JTE-522
      during the postinitiation stage, suggesting that its major anticancer action is
      at the postinitiation phase. However, JTE-522 had no effect on the size or
      invasive extent of tubular adenocarcinomas. Furthermore, microarray analyses
      revealed that JTE-522 had no effect on gene expression levels in DMH-induced
      tubular adenocarcinomas. These findings suggest that JTE-522 possesses
      chemopreventive activity against induction but not progression of tubular
      adenocarcinomas in rat colon. In view of the significant inhibitory effects of
      JTE-522 on ACF, its major anticancer action may occur in the postinitiation stage
      but before the malignant conversion stage of DMH-induced colon carcinogenesis.

PMID- 15455345
TI  - Serum testosterone levels and breast cancer recurrence.
AB  - Prospective studies show that high serum levels of androgens and estrogens are
      associated with increased incidence of postmenopausal breast cancer. The aim of
      the present analysis was to study the prognostic value of serum testosterone,
      estradiol and related factors in postmenopausal breast cancer patients. One
      hundred and ten patients without clinical recurrence were included in the study.
      After 5.5 years of follow-up, 31 patients developed distant metastasis (16),
      local relapse (4), or contralateral breast cancer (11). The risk of adverse
      events in relation to hormone level was examined by Cox' proportional hazard
      modeling, adjusting for hormone receptor status and stage at diagnosis. Body mass
      index and serum levels of testosterone, estradiol and glucose were significantly
      higher in patients who recurred than those who did not. The hazard ratios were
      1.8 (95% CI = 0.5-6.3) for the middle and 7.2 (95% CI = 2.4-21.4) for the upper
      tertiles of baseline testosterone distribution. Other hormones had only minor
      influence on prognosis. High testosterone predicts breast cancer recurrence.
      Further studies are required to determine whether dietary or other medical
      intervention to reduce testosterone can reduce the recurrence of breast cancer.

PMID- 15455346
TI  - Transcriptome analysis of a human colorectal cancer cell line shows molecular
      targets of insulin-like growth factor-binding protein-4 overexpression.
AB  - Insulin-like growth factor II (IGF-II) is expressed commonly in colorectal
      tumors. IGF-binding protein-4 (IGFBP-4) counteracts the tumor promoting
      activities of IGF-II by binding this growth factor. We have shown previously that
      in LS1034 cells, which highly express IGF-II, overexpression of IGFBP-4 led to a
      strong reduction in proliferation, colony formation and invasive capacity. To
      investigate the effects of IGFBP-4 at the molecular level we analyzed growth
      parameters of LS1034 human colon cancer cells vs. cells expressing the murine
      IGFBP-4 (mIGFBP-4) and used a subtractive cDNA library approach in combination
      with cDNA array hybridization to detect changes in the mRNA expression profiles.
      The mRNA levels for several proteins that are known to affect important
      biological properties of neoplastic cells, such as proteolysis, proliferation and
      differentiation were altered by overexpression of IGFBP-4. Transcript levels for
      tumor markers, like the carcinoembryonic antigen-related cell adhesion molecule
      (CEACAM), were reduced by elevated mIGFBP-4. Changes at the mRNA level were
      confirmed by Western blotting for CST1 (proteolysis or protease inhibitor), COX-2
      (cell motility) and CEACAM5 (tumor marker). Furthermore, the effect of mIGFBP-4
      on apoptosis was investigated and no increase of apoptosis could be detected in
      the IGFBP-4 overexpressing LS1034 cells. Our data indicate that IGFBP-4 is
      involved in the regulation of gene products that are known or supposed to be
      important for the pathogenesis of colon cancer cells.

PMID- 15455347
TI  - Association of prostate cancer family history with histopathological and clinical
      characteristics of prostate tumors.
AB  - Genetic factors may be used not only to assess risk of prostate cancer
      development but also to evaluate prostate cancer outcomes including clinical
      prognosis, treatment methods, and treatment response. To assess the role of
      family history on prostate cancer outcomes, we evaluated tumor characteristics,
      diagnostic precursors and biochemical (prostate specific antigen) relapse-free
      survival in men with and without a family history of prostate cancer. A total of
      684 prostate cancer cases unselected for family history were identified from an
      ongoing hospital based prostate cancer case-control study between 1995 and 2002.
      Self-reported family history was grouped within the following categories: none,
      any, moderate (one affected first or second degree relative) and high (2 or more
      affected first or second degree relatives). We further considered groups defined
      by early (before age 60) and late (after age 60) age at diagnosis. Overall, tumor
      stage was not significantly associated with any (odds ratio [OR] = 1.43 95%
      confidence interval [CI] = 1.00-2.05) or moderate (OR = 1.48, 95% CI = 1.0-2.19)
      family histories. Men diagnosed before age 60, however, had higher tumor stages
      if they had any (OR = 2.19, 95% CI = 1.28-3.75) or moderate (OR = 2.15, 95% CI =
      1.2-3.9) family histories. Men diagnosed after age 60 with any family history
      were significantly more likely to experience biochemical (PSA) failure (Hazard
      ratio [HR] = 2.60, 95%CI = 1.08-6.25). Men with any and moderate family histories
      were at significantly increased risk of biochemical failure (HR = 2.49, 95%CI =
      1.25-4.95 and HR = 2.46, 95% CI = 1.17-5.16, respectively). Moderate family
      history increased probability of seminal vesicle invasion (OR = 2.14, 95%CI =
      1.06-4.34). Our results suggest that a family history of prostate cancer may be
      associated with predictors of clinical outcome in prostate cancer cases
      unselected for a family history of prostate cancer.

PMID- 15455348
TI  - Fruits, vegetables and risk of renal cell carcinoma: a prospective study of
      Swedish women.
AB  - Findings of epidemiologic studies on the relationship between fruit and vegetable
      consumption and renal cell carcinoma (RCC) risk have been inconclusive. To study
      the association between fruits and vegetables and risk of RCC in a population
      based prospective cohort study of Swedish women, we collected dietary information
      from 61,000 women age 40-76 years by a food-frequency questionnaire. During 13.4
      years of follow-up 122 women developed RCC. Cox proportional hazards models were
      used to estimate relative risks (RR) with 95% confidence interval (CI). Women
      consuming 5 or more servings of fruit and vegetables daily had a relative risk of
      0.59 (95% CI = 0.26-1.34) in comparison to them consuming less than once daily.
      When fruits and vegetables were examined separately, those who consumed more than
      75 servings per month of fruits or vegetables had multivariate relative risk of
      0.59 (95% CI = 0.27-1.25) and 0.60 (95% CI = 0.31-1.17) respectively, compared to
      those consuming 11 or less servings per month. Within the group of fruits, the
      strongest inverse association was observed for banana (p = 0.07 by Wald test).
      The risk of RCC increased monotonically with increasing intake frequencies of
      fruit juice (p-value for trend = 0.10). Within the group of vegetables, the
      strongest inverse association was observed for root vegetables (p = 0.03 by Wald
      test). The risk of RCC decreased with increasing consumption frequencies of white
      cabbage (p for trend = 0.07). Frequent consumption of salad vegetables (once or
      more per day) decreased the risk by 40% (RR = 0.60; 95% CI = 0.30-1.22), in
      comparison to no consumption. Our results suggested that high consumption of
      fruits and vegetables might be associated with reduced risk of RCC.

PMID- 15455349
TI  - C609T polymorphism of the NAD(P)H:quinone oxidoreductase I gene does not
      significantly affect susceptibility for esophageal adenocarcinoma.

PMID- 15455350
TI  - Frequent promoter hypermethylation and low expression of the MGMT gene in
      oligodendroglial tumors.
AB  - Allelic losses on the chromosome arms 1p and 19q have been associated with
      favorable response to chemotherapy and good prognosis in anaplastic
      oligodendroglioma patients, but the molecular mechanisms responsible for this
      relationship are as yet unknown. The DNA repair enzyme O(6)-methylguanine DNA
      methyltransferase (MGMT) may cause resistance to DNA-alkylating drugs commonly
      used in the treatment of anaplastic oligodendrogliomas and other malignant
      gliomas. We report on the analysis of 52 oligodendroglial tumors for MGMT
      promoter methylation, as well as mRNA and protein expression. Using sequencing of
      sodium bisulfite-modified DNA, we determined the methylation status of 25 CpG
      sites within the MGMT promoter. In 46 of 52 tumors (88%), we detected MGMT
      promoter hypermethylation as defined by methylation of more than 50% of the
      sequenced CpG sites. Real-time reverse transcription-PCR showed reduced MGMT mRNA
      levels relative to non-neoplastic brain tissue in the majority of tumors with
      hypermethylation. Similarly, immunohistochemical analysis showed either no or
      only small fractions of MGMT positive tumor cells. MGMT promoter hypermethylation
      was significantly more frequent and the percentage of methylated CpG sites in the
      investigated MGMT promoter fragment was significantly higher in tumors with loss
      of heterozygosity on chromosome arms 1p and 19q as compared to tumors without
      allelic losses on these chromosomes arms. Taken together, our data suggest that
      MGMT hypermethylation and low or absent expression are frequent in
      oligodendroglial tumors and likely contribute to the chemosensitivity of these
      tumors.

PMID- 15455351
TI  - Antitumor activity of the intratumoral injection of fowlpox vectors expressing a
      triad of costimulatory molecules and granulocyte/macrophage colony stimulating
      factor in mesothelioma.
AB  - Deficiency in costimulatory molecule expression has been implicated in the
      ability of tumors to escape immune effectors. The activity of the intratumoral
      administration of recombinant fowlpox vectors expressing a triad of costimulatory
      molecules (rF-TRICOM) was evaluated in the asbestos-induced AB12 and AC29 mouse
      models of mesothelioma. Mesothelioma cell infected with rF-TRICOM expressed high
      levels of the costimulatory molecules. Prolongation of survival was observed in
      mice receiving rF-TRICOM in AB12 and AC29 intraperitoneal models. Complete tumor
      regressions were observed in mice receiving intratumoral rF-TRICOM in the AB12
      subcutaneous tumor model. Tumor regressions were associated with the development
      of serum IgG reactivities to mesothelioma-associated determinants and specific
      systemic cytolytic activity, and responding mice were capable of rejecting tumors
      upon re-challenge. Antitumor activity was also observed in mice with established
      AB12 tumor vaccinated with irradiated rF-TRICOM-infected AB12 cells. The
      antitumor activity of intratumoral rF-TRICOM was superior to that of the
      intratumoral injection of a fowlpox vector expressing granulocyte-macrophage
      colony stimulating factor (rF-GM-CSF). AB12 and AC29 tumors were found to produce
      GM-CSF and to have substantial macrophage infiltration. Production of GM-CSF
      decreased in vivo in tumors injected with rF-TRICOM. rF-TRICOM and wild-type
      fowlpox inhibited the growth of AB12 and AC29 cells in vitro; less inhibition was
      observed with rF-GM-CSF. These results indicate that the intratumoral injection
      of rF-TRICOM has significant activity in mouse models of mesothelioma and can
      elicit a systemic antitumor immune response. The results also suggest potential
      limitations to the intratumoral administration of cytokines, such as GM-CSF, in
      mesothelioma.

PMID- 15455352
TI  - Maternal human polyomavirus infection and risk of neuroblastoma in the child.
AB  - To investigate if polyomavirus infection during pregnancy is linked to
      development of neuroblastoma in the child, serum samples of 115 index mothers
      from the pregnancy where the child eventually developed neuroblastoma were
      identified and matched with serum samples from 8 control mothers per index
      mother. The samples were tested for specific IgG and IgM antibodies to BK and JC
      virus using enzyme immunoassays based on purified yeast-expressed virus-like
      particles (VLPs). The serum samples as well as 10 neuroblastoma cell lines were
      also analyzed using Real Time (TaqMan) PCR for detection and quantification of BK
      virus DNA. The BK virus IgG seroprevalence was similar among index mothers (80%)
      and control mothers (83%) [OR 0.8; 95% confidence interval (95% CI): 0.5-1.3]. BK
      virus IgM was also not associated with neuroblastoma risk (OR was OR = 0.6; 95%
      with CI, 0.2-1.9). Also JC virus had no association, neither for IgG (OR = 0.9;
      95% CI, 0.6-1.4) nor for IgM (OR = 0.9; 95% CI, 0.4-1.9). All serum samples and
      all neuroblastoma cell lines were negative for BKV DNA. In summary, a
      comprehensive cohort using both serology and polyomavirus DNA detection found no
      evidence for association between BKV or JCV polyomaviruses and neuroblastoma.

PMID- 15455353
TI  - Epstein-Barr virus-encoded latent membrane protein 1 promotes stress-induced
      apoptosis upstream of caspase-2-dependent mitochondrial perturbation.
AB  - Previous studies have shown that Epstein-Barr virus (EBV)-encoded latent membrane
      protein 1 (LMP1) enhances etoposide-induced apoptosis in epithelial cells. Our
      study was undertaken to further dissect the modulation of tumor cell apoptosis by
      this viral protein. Using an inducible system of LMP1 expression in HeLa cells,
      we show herein that etoposide-triggered apoptosis, as evidenced by nuclear
      condensation and caspase-3 activation, is enhanced by LMP1. LMP1 also potentiates
      etoposide-induced processing and activation of caspase-2 in this model and
      enhances the dissipation of mitochondrial transmembrane potential and the release
      of cytochrome c in response to etoposide. Moreover, cisplatin-triggered
      activation of caspases 2 and 3 is potentiated upon expression of LMP1. A similar
      LMP1-mediated enhancement of cisplatin-induced caspase activation was seen upon
      stable transfection of wild-type LMP1 into the nasopharyngeal carcinoma cell
      line, TW03. Finally, using deletion mutants of LMP1 to determine the region of
      LMP1 required for apoptosis potentiation, we found that amino acids 350-386
      (located within the CTAR2 domain) were responsible for sensitizing cells to
      cisplatin. We conclude that LMP1-dependent potentiation of stress-induced
      apoptosis occurs at an early step in the apoptosis cascade, upstream of the
      activation of caspase-2, and involves the C-terminal signaling domain of LMP1.
      These findings could have important ramifications for the treatment of EBV
      associated malignancies of epithelial origin, including nasopharyngeal carcinoma.

PMID- 15455354
TI  - Involvement of the chaperone tapasin in HLA-B44 allelic losses in colorectal
      tumors.
AB  - Tumors can exhibit selective allelic losses of HLA class I antigens as part of
      altered HLA phenotypes. In colorectal tumors, the HLA class I allele most
      frequently lost is HLA-B44, although the precise mechanism responsible for this
      loss has not been described to date. From a total of 95 colorectal cryopreserved
      tumor samples, we selected (by immunohistochemical staining) 13 tumors with HLA
      B44-negative expression. Loss of heterozygosity at 6p21.3 was demonstrated to be
      the cause of the negative expression in 4 cases. In the remaining 9 cases,
      structural analyses of microdissected tissue samples of the 3 subtypes of HLA-B44
      loss in these tumors (B*4402, B*4403 and B*4405) did not reveal any mutations.
      However, all 3 subtypes of HLA-B44 presented in this study shared a common
      characteristic: the presence of an aspartic amino acid residue at position 114 in
      the HLA class I heavy chain. This residue has been described as determining
      tapasin dependence for the surface expression of these alleles and therefore for
      antigen presentation. We studied tapasin transcription by RT-PCR in these tumors
      and found tapasin downregulation in all 9 tumors samples with the HLA-B44
      negative phenotype. In contrast, tapasin was normally transcribed in HLA-B44
      positive colorectal tumors samples, as well as in 3 HLA-B44-negative laryngeal
      carcinomas and 1 bladder tumor. Defective tapasin transcription seems to be an
      alteration responsible for the absence of HLA-B44 expression in colorectal
      tumors, thus contributing to the generation of tumor immune escape phenotypes.

PMID- 15455355
TI  - Coordinated downregulation of the antigen presentation machinery and HLA class
      I/beta2-microglobulin complex is responsible for HLA-ABC loss in bladder cancer.
AB  - Downregulation of MHC class I expression is a widespread phenomenon used by tumor
      cells to escape antitumor T-cell-mediated immune responses. These alterations may
      play a role in the clinical course of the disease. The aim of our study was to
      investigate the molecular mechanism underlying the absence of HLA-class I
      molecule expression in bladder cancer cells. Microdissected tumor tissues were
      characterized by real-time quantitative PCR for the expression of HLA-ABC, beta2
      microglobulin and the members of the antigen processing machinery (APM) of HLA
      class I molecules (LMP2, LMP7, TAP1, TAP2 and tapasin). Our results showed that
      irreversible HLA loss by mutations in the beta2-microglobulin gene was not the
      cause of low HLA class I expression in bladder cancers. In contrast, we observed
      a coordinated transcription downregulation of HLA-ABC and beta2-microglobulin and
      APM genes in microdissected tumor tissue derived from bladder carcinomas. This
      mechanism may represent a major factor for the downregulation of HLA class I
      expression and in the subsequent direct recognition of cancer cells by cytolytic
      T lymphocytes. Because this regulatory mechanism is frequently reversible by IFN
      gamma treatment, we conclude that HLA class I expression should be a major
      consideration for immunotherapeutic purposes in patients with bladder cancer.

PMID- 15455356
TI  - Isoform-specific expression of 14-3-3 proteins in human lung cancer tissues.
AB  - 14-3-3 Proteins play important roles in a wide range of vital regulatory
      processes, including signal transduction, apoptosis, cell cycle progression and
      DNA replication. In mammalian cells, 7 14-3-3 isoforms (beta, gamma, epsilon,
      eta, sigma, theta and zeta) have been identified and each of these seems to have
      distinct tissue localizations and isoform-specific functions. Previous studies
      have shown that 14-3-3 protein levels are higher in human lung cancers as
      compared to normal tissues. It is unclear, however, which of the 14-3-3
      isoform(s) are overexpressed in these cancers. In our study, the levels of all
      seven 14-3-3 isoforms were examined by RT-PCR and Western blotting. We show that
      the message for only two isoforms, 14-3-3epsilon and zeta, could be detected in
      normal tissues. In lung cancer biopsies, however, four isoforms, 14-3-3beta,
      gamma, sigma, and theta;, in addition to 14-3-3epsilon and zeta, were present in
      abundance. The expression frequency of 14-3-3beta, gamma, sigma and theta;
      isoforms was 11, 10, 13 and 8 of the 14 biopsies examined, respectively. The data
      from immunohistochemical staining and Western blotting were consistent with the
      RT-PCR results. Given the prevalence of elevated 14-3-3 expression in human lung
      cancers we propose that these proteins may be involved in lung cancer
      tumorigenesis and that specific 14-3-3 proteins may be useful as markers for lung
      cancer diagnosis and targets for therapy.

PMID- 15455357
TI  - Phase II study of paclitaxel and estramustine in patients with recurrent and
      refractory non-Hodgkin lymphoma.
AB  - BACKGROUND: The current study was conducted to evaluate the efficacy of
      paclitaxel, administered weekly or once every 3 weeks, in combination with oral
      estramustine phosphate (EMP) in patients with recurrent or refractory aggressive
      non-Hodgkin lymphoma (NHL). METHODS: Between February 1996 and February 2001, 23
      patients with recurrent NHL were enrolled onto this Phase II trial. The median
      age for all patients was 65 years (range, 27-80 years). The initial 12 patients
      (who received a mean number of 2.4 prior treatments, including 1 patient who
      received a prior peripheral blood stem cell transplant) received paclitaxel at a
      dose of 175 mg/m2 given as a 3-hour intravenous infusion every 21 days. The next
      11 patients (who received a mean number of 2.8 prior treatments, including 1
      patient who received prior peripheral blood stem cell transplant) were registered
      (1 patient refused treatment) to receive paclitaxel at a dose of 80 mg/m2 as a 1
      hour intravenous infusion weekly for 6 weeks of an 8-week cycle. All patients
      received EMP at a dose of 600 mg/m2 orally per day beginning the day prior to
      each dose of paclitaxel for a total of 3 days. RESULTS: When paclitaxel was
      administered every 21 days, 4 partial responses were observed in 12 evaluable
      patients (33.3%). The median survival was 147 days. The median duration of
      response was 102 days (range, 42-127 days) and the median time to disease
      progression was 66 days. Grade 3 and Grade 4 neutropenia (according to the
      revised version of the Common Toxicity Criteria of the National Cancer Institute)
      were observed in 5 patients (42%) in this group. In an attempt to reduce the
      incidence of myelosuppression, paclitaxel dosing was changed to weekly dosing. In
      the cohort of patients receiving weekly paclitaxel, an objective response was
      reported to occur in 3 (1 complete response and 2 partial responses) of 11
      evaluable patients (27%). The median survival was 132 days (range, 33-462 days).
      The median duration of response was 64 days and the median time to disease
      progression was 57 days. There was no significant difference noted between the
      cohort receiving paclitaxel three times weekly and those receiving paclitaxel
      weekly with regard to overall survival and time to disease progression (P = 0.7
      and P = 0.8, respectively by the log-rank test). Grade 3 or 4 neutropenia was
      observed in only 2 of 11 patients (18%) in the weekly paclitaxel group. There
      were no significant differences noted in terms of thrombocytopenia, anemia,
      nausea, anorexia, or fatigue between the treatment groups. CONCLUSIONS:
      Paclitaxel given once weekly or three times weekly, in combination with oral EMP,
      was found to have comparable efficacy in patients with recurrent NHL, with an
      overall response rate of 30%. The response rate was found to be higher than that
      reported in prior studies of paclitaxel as a single agent in the treatment of
      NHL, suggesting that EMP may enhance paclitaxel efficacy in patients with NHL.
      Hematologic toxicity was diminished when paclitaxel was administered on a weekly
      schedule. The minimal myelotoxicity of weekly paclitaxel makes this a potentially
      attractive agent for combination regimens for patients with recurrent/refractory
      NHL.

PMID- 15455358
TI  - Iodine-131 metaiodobenzylguanidine treatment for metastatic carcinoid. Results in
      98 patients.
AB  - BACKGROUND: Iodine-131 metaiodobenzylguanidine (131I-MIBG) is useful for imaging
      carcinoid tumors and recently has been applied to the palliative treatment of
      metastatic carcinoid in small studies. The authors now report their results on
      the therapeutic utility of high-dose 131I-MIBG treatment in a large group of
      patients with metastatic carcinoid tumors. METHODS: The authors performed a
      retrospective review of 98 patients with metastatic carcinoid who were treated at
      their institution with 131I-MIBG over a 15-year period. Endpoints examined
      included the World Health Organization criteria for treatment response: symptoms,
      hormone (5-hydroxyindoleacetic acid [5-HIAA]) production, and clinical tumor
      response. RESULTS: Patients received a median dose of 401 +/- 202 millicuries
      (mCi) 131I-MIBG. The median survival after treatment was 2.3 years. Patients who
      experienced a symptomatic response had improved survival (5.76 years vs. 2.09
      years; P < 0.01). For the 56 patients who had 5-HIAA levels monitored, the mean
      urine 5-HIAA levels decreased significantly after 131I-MIBG treatment (126 +/-
      122 ng/mL vs. 91 +/- 125 ng/mL; P < 0.01); however, the patients with reduced 5
      HIAA levels did not experience improved survival (4.11 years vs. 3.42 years; P =
      0.2). Patients who received an initial 131I-MIBG dose > 400 mCi lived longer than
      patients who received < 400 mCi (4.69 years vs. 1.86 years; P = 0.05).
      Radiographic tumor response did not predict survival. Toxicity included
      pancytopenia, thrombocytopenia, nausea, and emesis. CONCLUSIONS: The current data
      support 131I-MIBG treatment in select patients with metastatic carcinoid who
      progress despite optimal medical management. Improved survival was predicted best
      by symptomatic response to 131I-MIBG treatment, but not by hormone or
      radiographic response.

PMID- 15455359
TI  - Pulmonary adenocarcinoma is associated with poor long-term survival after
      surgical resection. Effect of allogeneic blood transfusion.
AB  - BACKGROUND: The significance of allogeneic blood transfusion in the prognosis of
      patients with nonsmall lung carcinoma (NSCLC) remains controversial. Reports have
      suggested that patients with adenocarcinoma have a worse prognosis from cancer
      than patients with squamous cell carcinoma (SCC), but this evidence is lacking in
      NSCLC. The objective of the current study was to elucidate the correlation
      between perioperative allogeneic blood transfusion and the prognosis in patients
      with adenocarcinoma and SCC. METHODS: The study group comprised 329 consecutive
      patients (172 men and 157 women) with a mean age of 67 years who underwent lung
      resection between 1996 and 2003 in 1 unit. The clinicopathologic and survival
      data were compared between 62 patients (42.7%) with adenocarcinoma and 58
      patients (48.3%) with SCC who received a perioperative blood transfusion and 83
      patients (57.3 %) with adenocarcinoma and 126 patients (61.3%) with SCC who did
      not. RESULTS: The overall surgical mortality rate was 3.9% (13 deaths). The
      median surgical blood loss was 380 mL (range, 125-4500 mL). The mean blood
      transfusion received was 1.9 U (range, 0-8 U). The overall actuarial 1, 3, and 5
      year survival rates in the adenocarcinoma and SCC groups were 82.3%, 49.6%, and
      19.4% and 87.9%, 71.7%, and 32.7%, respectively (P = 0.021). Multivariate
      analysis demonstrated that the factors that appeared to be independent prognostic
      factors in both groups were T-classification (P < 0.001), lymph node metastasis
      (P < 0.001), and postoperative complications (P = 0.029). Perioperative blood
      transfusion was not an independent prognostic indicator in either group.
      CONCLUSIONS: The current study demonstrated that long-term survival in patients
      with adenocarcinoma of the lung was significantly worse compared with patients
      with SCC, but was independent of allogeneic perioperative blood transfusion. The
      results reaffirmed the importance of tumor invasion and lymph node involvement in
      the overall poor prognosis of these patients.

PMID- 15455360
TI  - Systematic review of sacral nerve stimulation for faecal incontinence and
      constipation.
AB  - BACKGROUND AND METHOD: This systematic review assesses the efficacy and safety of
      sacral nerve stimulation (SNS) for faecal incontinence and constipation.
      Electronic databases and selected websites were searched for studies evaluating
      SNS in the treatment of faecal incontinence or constipation. Primary outcome
      measures included episodes of faecal incontinence per week (faecal incontinence
      studies) and number of evacuations per week (constipation studies). RESULTS: From
      106 potentially relevant reports, six patient series and one crossover study of
      SNS for faecal incontinence, and four patient series and one crossover study of
      SNS for constipation, were included. After implantation, 41-75 per cent of
      patients achieved complete faecal continence and 75-100 per cent experienced
      improvement in episodes of incontinence. There were 19 adverse events among 149
      patients. The small crossover study reported increased episodes of faecal
      incontinence when the implanted pulse generator was switched off. Case series of
      SNS for constipation reported an increased frequency of evacuation. There were
      four adverse events among the 20 patients with a permanent implant. The small
      crossover study reported a reduced number of evacuations when the pulse generator
      was switched off. CONCLUSION: SNS results in significant improvement in faecal
      incontinence in patients resistant to conservative treatment. Early data also
      suggest benefit in the treatment of constipation.

PMID- 15455361
TI  - Beneficial effect of helicopter emergency medical services on survival of
      severely injured patients.
AB  - BACKGROUND: In Rotterdam, the Netherlands, a helicopter-transported medical team
      (HMT), staffed with a trauma physician, provides additional therapeutic options
      at the scene of injury. This study evaluated the influence of the HMT on the
      chance of survival of severely injured trauma victims. METHODS: This was a 2-year
      prospective observational study of consecutive adults who suffered multiple
      trauma (Injury Severity Score (ISS) 16 or more) and presented to the Erasmus
      Medical Centre emergency ward. The effect of the HMT was quantified by an odds
      ratio (OR), adjusted for confounding variables in logistic regression models.
      RESULTS: Complete data for a total of 346 patients were available for analysis.
      Two hundred and thirty-nine patients were treated by ambulance personnel alone
      and 107 received additional HMT assistance. Patients in the HMT group had
      significantly lower Glasgow Coma Scale scores (mean 8.9 versus 10.6; P = 0.001)
      and a higher ISS (mean 30.9 versus 25.3; P < 0.001). The unadjusted OR for death
      was 1.7 in favour of the group treated by ambulance staff only (OR for survival
      0.61 (95 per cent confidence interval (c.i.) 0.37 to 1.0, P = 0.048)). After
      adjustment, however, patients in the HMT group had an approximately twofold
      better chance of survival (all injuries: OR 2.2 (95 per cent c.i. 0.92 to 5.9), P
      = 0.076; blunt injuries: OR 2.8 (95 per cent c.i. 1.07 to 7.52), P = 0.036).
      CONCLUSION: The presence of the HMT may increase chances of survival for patients
      suffering multiple trauma, especially for those with blunt trauma.

PMID- 15455362
TI  - Abdominoperineal resection is associated with poor oncological outcome.
AB  - BACKGROUND: The aim of this study was to compare the operative results and
      oncological outcomes of patients who had mid or distal rectal cancer treated by
      abdominoperineal resection (APR) with those treated without sphincter ablation
      (non-APR). METHODS: Five hundred and four consecutive patients (308 men and 196
      women) with rectal cancer within 12 cm from the anal verge underwent radical
      resection with curative intent. Sharp mesorectal dissection was used. Operative
      results and long-term outcomes were compared between those treated by APR and
      those by non-APR. RESULTS: Sixty-nine patients had APR and 435 patients were
      treated with radical resection without perineal resection (anterior resection,
      419; Hartmann's operation, 16). The overall operative mortality and morbidity
      rates were 1.6 and 31.0 per cent respectively. Age, sex, duration of surgery,
      blood loss, duration of hospital stay, operative mortality and overall morbidity
      were similar in the two groups. Local recurrence was more frequent after curative
      APR than after non-APR (23 versus 10.2 per cent at 5 years; P = 0.010). Five-year
      cancer-specific survival rates after APR and non-APR were 60 and 74.0 per cent
      respectively (P = 0.006). APR was an independent factor for poor cancer-specific
      survival in multivariate analysis. CONCLUSION: Although postoperative mortality
      and morbidity rates were similar in patients with or without sphincter ablation,
      local control and survival were worse in those treated by APR.

PMID- 15455363
TI  - Resection of the rectum and total excision of the internal anal sphincter with
      smooth muscle plasty and colonic pouch for treatment of ultralow rectal
      carcinoma.
AB  - BACKGROUND: Intersphincteric resection can provide tumour-free margins for rectal
      tumours located 0-1 cm above the dentate line. However, the internal anal
      sphincter (IAS) is partially or totally resected and some degree of anal
      incontinence may develop. A novel technique of smooth muscle plasty of the IAS
      and colonic pouch construction is described, along with an assessment of
      morbidity, oncological results and functional outcome. PATIENTS AND METHODS:
      Between 1997 and 2002, 27 patients (16 men; median age 55 (range 26-75) years)
      were operated on for T2-3 N0-1 M0 rectal carcinoma located a median of 1.0 (range
      0.5-1.5) cm from the dentate line. Resection of the IAS was performed
      transanally. A smooth muscle cuff, fashioned from the muscular layer of colon,
      and a colonic pouch were used for anorectal reconstruction. RESULTS: There were
      no perioperative deaths. Anastomotic leakage developed in two patients. After a
      median follow-up of 38 (range 14-66) months no local recurrence was detected.
      Distant metastases occurred in three patients, two of whom died. Perfect
      functional outcome was achieved in 22 of 26 patients. At 6 months after surgery
      the mean(s.d.) resting anal pressure was 49(8) mmHg. CONCLUSION: In selected
      patients intersphincteric resection does not compromise the oncological result.
      The suggested anorectal reconstruction may improve the functional outcome.

PMID- 15455364
TI  - Ethical issues in identifying and recruiting participants for familial genetic
      research.
AB  - Family-based research is essential to understanding the genetic and environmental
      etiology of human disease. The success of family-based research often depends on
      investigators' ability to identify, recruit, and achieve a high participation
      rate among eligible family members. However, recruitment of family members raises
      ethical concerns due to the tension between protecting participants' privacy and
      promoting research quality, and guidelines for these activities are not well
      established. The Cancer Genetics Network Bioethics Committee assembled a
      multidisciplinary group to explore the scientific and ethical issues that arise
      in the process of family-based recruitment. The group used a literature review as
      well as expert opinion to develop recommendations about appropriate approaches to
      identifying, contacting, and recruiting family members. We conclude that there is
      no single correct approach, but recommend a balanced approach that takes into
      account the nature of the particular study as well as its recruitment goals.
      Recruitment of family members should be viewed as part of the research protocol
      and should require appropriate informed consent of the already-enrolled
      participant. Investigators should inform prospective participants why they are
      being contacted, how information about them was obtained, and what will happen to
      that information if they decide not to participate. The recruitment process
      should also be sensitive to the fact that some individuals from families at
      increased genetic risk will have no prior knowledge of their risk status. These
      recommendations are put forward to promote further discussion about the
      advantages and disadvantages of various approaches to family-based recruitment.
      They suggest a framework for considering alternative recruitment strategies and
      their implications, as well as highlight areas in need of further empirical
      research.

PMID- 15455365
TI  - Ganglioglioma in a Sotos syndrome patient with an NSD1 deletion.
AB  - Sotos syndrome, a disorder with macrocephaly, mental delay, and facial anomalies,
      has been noted to have an increased risk of neoplasia. Here, we report a patient
      with a microdeletion in nuclear receptor SET-domain-containing protein (NSD1) and
      a previously undescribed intracranial ganglioglioma.

PMID- 15455366
TI  - Acute phase lipocalin Ex-FABP is involved in heart development and cell survival.
AB  - Ex-FABP is an extracellular fatty acid binding protein, expressed during chicken
      embryo development in cartilage, muscle fibers, and blood granulocytes.
      Transfection of chondrocytes and myoblasts with anti-sense Ex-FABP cDNA results
      in inhibition of cell proliferation and apoptosis induction. Ex-FABP expression
      is dramatically enhanced by inflammatory stimuli and in pathological conditions.
      In this paper, by in situ whole mount and immunohistochemistry analysis we show
      that, at early developmental stage, Ex-FABP is diffuse in all tissues of chick
      embryos. Particularly high level of transcript and protein are expressed in the
      heart. During acute phase response (APR) induced by endotoxin LPS injection, a
      marked increase of Ex-FABP mRNA was observed in embryos, highest Ex-FABP
      expression being in heart and liver. To investigate in vivo the biological role
      of Ex-FABP, we have directly microinjected chicken embryos with antibody against
      Ex-FABP. Almost 70% of chicken embryos died and the target tissue was the heart.
      We detected in heart of the treated embryos a significant increase of apoptotic
      cells and high level of fatty acids. We propose that the accumulation of fatty
      acid, specific ligand of Ex-FABP, in the cell microenvironment is responsible of
      heart cell death, and we suggest that Ex-FABP may act as a survival protein by
      playing a role as scavenger for fatty acids.

PMID- 15455367
TI  - Thermal risks from LED- and high-intensity QTH-curing units during polymerization
      of dental resins.
AB  - The aim of this study was to test the ability of an infrared (IR) camera to
      assess temperature changes and distributions in teeth below restorations when
      quartz-tungsten-halogen (QTH) and light-emitting diode (LED) curing lights were
      used to photopolymerize the restorative material. Our hypothesis was that the
      higher power density and broader spectral distribution of the QTH source would
      cause greater increases in tooth temperature than the LED source, and that these
      differences would be best demonstrated with the IR camera. Cavities were prepared
      on human third molars and restored with a resin composite restorative material.
      The material was light-cured using three light-curing sources using several
      exposure times. The external (outside the tooth) and internal (inside the pulp
      chamber) temperature changes during polymerization of the composite material were
      recorded over 360 s with thermocouples and an IR camera. Using thermocouples the
      maximum increase in external temperature (+17.7 degrees C) was reported for the
      Swiss Master light after 20 s of curing time while the minimum temperature rise
      (+7.8 degrees C) was reported for the Freelight 2. Whereas a 2.6 degrees C
      increase in internal temperature was observed after curing 20 s with the
      Freelight 2, 7.1 degrees C was reported after 60 s of light exposure to Astralis
      10. Infrared images showed similar trends in external-internal rises in
      temperature as the thermocouples, although temperatures measured by the IR were
      generally higher. These results indicate that the higher power density QTH
      sources caused greater increases in tooth temperatures than the LED source and
      that thermocouples may underestimate the heat applied to the tooth.

PMID- 15455368
TI  - Tensile properties and biological response of poly(L-lactic acid) felt graft: an
      experimental trial for rotator-cuff reconstruction.
AB  - Poly(L-lactic acid) felt (PLLA felt) was prepared for reconstruction of the
      rotator cuff in animal models. Small changes were found in the tensile strength
      of both the cultured PLLA felt and the PLLA felt implanted on the paravertebral
      muscle of rabbits up to 16 postoperative weeks. The stiffness of the felt
      implanted on the muscle from 6 to 16 weeks showed a statistically significant
      increase. When the infraspinatus tendons of beagle dog were reconstructed with
      the PLLA felt, the ultimate strength of PLLA felt increased threefold, and the
      stiffness increased fivefold by 16 postoperative weeks compared to that of the
      initial PLLA felt. They were statistically significant (p < 0.01). All the
      implanted specimens ruptured at the junction between the bone and the PLLA felt.
      Histological examination demonstrated infiltration of fibrous tissue into the
      interstices of the PLLA felt fibers. Connection between the infraspinatus tendon
      and the PLLA felt was tight with the formed scar tissue, but the connective
      tissue between the bone and PLLA felt fibers was sparse even at 16 and 32
      postoperative weeks. A few deteriorated PLLA felt fibers were observed at 32
      postoperative weeks. It was concluded that the degradation rate of PLLA felt was
      low and the tensile recovery of the PLLA felt graft in beagle dogs was excellent.
      Thus, PLLA felt might be a useful bioabsorbable material for rotator-cuff
      reconstruction.

PMID- 15455369
TI  - Effects of different sterilization methods on the morphology, mechanical
      properties, and cytotoxicity of chitosan membranes used as wound dressings.
AB  - The aim of this work was to compare the effects induced by two different
      sterilization methods (exposure to gamma radiation or ethylene oxide) and an
      antiseptic technique (immersion in 70% ethanol aqueous solution) on the
      morphology, tensile strength, percentage of strain at break, and in vitro
      cytotoxicity to Vero cells on chitosan membranes designed for wound healing. Four
      distinct membrane compositions were evaluated, with chitosan, glycerol, and
      chitin used as components. Gamma radiation, in spite of being one of the most
      commonly employed sterilizing agents, negatively affected the morphology of
      membranes composed solely by chitosan as well as the percentage of strain at
      break of the chitosan-membranes containing glycerol on their composition.
      Moreover, its use affected the color of the chitosan membranes. The use of 70%
      ethanol aqueous solution did not change the chitosan-membrane characteristics
      significantly, but its use has limitations concerning the process scale up. With
      ethylene oxide (EtO), chitosan-membrane morphology, percentage of strain at
      break, and in vitro cytotoxicity to Vero cells were not significantly affected.
      The tensile strength of the membranes containing chitin were reduced after the
      treatment with ethylene oxide; however, the obtained values were comprised in the
      range verified for normal human skin. Therefore, because the final
      characteristics of the membranes treated with ethylene oxide are appropriate when
      considering their use as wound healing devices, and because this sterilization
      process is easily adjusted to use on an industrial scale, EtO can be considered
      the most adequate sterilizing agent for chitosan membranes. However, it should be
      considered that this chemical is associated with toxicity, flammability, and
      environmental risks, as well as with possible material contamination with
      ethylene oxide residues.

PMID- 15455370
TI  - Resin penetration through submicrometer hiatus structures: a SEM and CLSM study.
AB  - The purpose of this study was to confirm the existence of submicrometer hiatus
      structures and to examine the degree of resin penetration through these
      formations. Dentin disks 2.0 mm in thickness were sectioned from 48 human molars
      with the use of a microtome saw. Three different fifth-generation (total-etch,
      combined primer/resin) dentin adhesive systems were used to bond a light-cured,
      resin-based composite to the dentin disks (n = 16 each group). Bonded disks from
      the three groups were then sectioned. Half of each group was examined with the
      use of a scanning electron microscope (SEM) (n = 8), and the other half with the
      use of a confocal laser scanning microscope (CLSM) (n = 8). The frequency of
      submicrometer hiatus formation was recorded and documented with associated
      imaging techniques. Resin penetration within submicrometer hiati were observed in
      41.7% (10/24) of SEM specimens and 83.3% (20/24) of CLSM specimens. The location
      and size of these structures were found to be quite uniform. Submicrometer hiati
      approximated 200 microm in each of the three dentin bonding systems examined.
      Resin penetration through submicrometer hiati does not appear to be an artifact
      of desiccation. These structures were clearly identified within the hybrid layer
      of each dentin adhesive system used in this study.

PMID- 15455371
TI  - Breast cancer risk associated with genotype polymorphism of the catechol estrogen
      metabolizing genes: a multigenic study on cancer susceptibility.
AB  - Estrogen has been suggested to trigger breast cancer development via an
      initiating mechanism involving its metabolite, catechol estrogen (CE). To examine
      this hypothesis, we carried out a multigenic case-control study of 469 incident
      breast cancer patients and 740 healthy controls to define the role of important
      genes involved in the different metabolic steps that protect against the
      potentially harmful effects of CE metabolism. We studied the 3 genes involved in
      CE detoxification by conjugation reactions involving methylation (catechol-O
      methyltransferase, COMT), sulfation (sulfotransferase 1A1, SULT1A1), or
      glucuronidation (UDP-glucuronosyltransferase 1A1, UGT1A1), one (manganese
      superoxide dismutase, MnSOD) involved in protection against reactive oxidative
      species-mediated oxidation during the conversion of CE-semiquinone (CE-SQ) to CE
      quinone (CE-Q), and 2 of the glutathione S-transferase superfamily, GSTM1 and
      GSTT1, involved in CE-Q metabolism. Support for this hypothesis came from the
      observations that (i) there was a trend toward an increased risk of breast cancer
      in women harboring a greater number of putative high-risk genotypes of these
      genes (p < 0.05); (ii) this association was stronger and more significant in
      those women who were more susceptible to estrogen [no history of pregnancy or
      older (> or =26 years) at first full-term pregnancy (FFTP)]; and (iii) the risks
      associated with having one or more high-risk genotypes were not the same in women
      having experienced different menarche-to-FFTP intervals, being more significant
      in women having been exposed to estrogen for a longer period (> or =12 years)
      before FFTP. Furthermore, because CE-Q can attack DNA, leading to the formation
      of double-strand breaks (DSB), we examined whether the relationship between
      cancer risk and the genotypic polymorphism of CE-metabolizing genes was modified
      by the genotypes of DSB repair genes, and found that a joint effect of CE
      metabolizing genes and one of the two DSB repair pathways, the homologous
      recombination pathway, was significantly associated with breast cancer
      development. Based on comprehensive CE metabolizing gene profiles, our study
      provides support to the hypotheses that breast cancer can be initiated by
      estrogen exposure and that increased estrogen exposure confers a higher risk of
      breast cancer by causing DSB to DNA.

PMID- 15455372
TI  - Green tea constituent epigallocatechin-3-gallate selectively inhibits COX-2
      without affecting COX-1 expression in human prostate carcinoma cells.
AB  - Overexpression of cyclooxygenase (COX)-2 has been implicated in many pathologic
      conditions, including cancer. One practical inference of this finding is that
      sustained inhibition of COX-2 could serve as a promising target for prevention or
      therapy of cancer. Conventional nonsteroidal antiinflammatory drugs (NSAIDs) and
      recently developed COX-2-specific inhibitors have shown considerable promise in
      prevention of some forms of human cancer; however, its application is limited due
      to severe toxic side effects on normal cells. Therefore, there is a need to
      define novel, nontoxic dietary constituents with proven chemopreventive effects
      through other pathways that also possess COX-2 but not COX-1 inhibitory activity.
      Recent studies on green tea and its major polyphenolic constituent (
      )epigallocatechin-3-gallate (EGCG) have established its remarkable cancer
      preventive and some cancer therapeutic effects. Here, we show that EGCG inhibits
      COX-2 without affecting COX-1 expression at both the mRNA and protein levels, in
      androgen-sensitive LNCaP and androgen-insensitive PC-3 human prostate carcinoma
      cells. Based on our study, it is tempting to suggest that a combination of EGCG
      with chemotherapeutic drugs could be an improved strategy for prevention and
      treatment of prostate cancer.

PMID- 15455373
TI  - Reactivation of SYK expression by inhibition of DNA methylation suppresses breast
      cancer cell invasiveness.
AB  - The gene product of spleen tyrosine kinase (SYK) has been implicated in the
      suppression of breast cancer invasion. We previously reported that SYK expression
      is lost in a subset of breast cancer; primarily by methylation-mediated gene
      silencing. In our study, we explored the possibility of using a DNA
      methyltransferase inhibitor, 5-aza-2'-deoxycytidine (AZA), to suppress breast
      cancer cell invasion by restoring SYK expression. We found that AZA treatment
      reestablished the expression of SYK(L) that was accompanied by suppression of the
      invasion capacity of SYK-negative cells. This invasion inhibition was not due to
      global cellular toxicity since this treatment did not affect overall cell
      proliferation. This decreased invasiveness by AZA treatment was diminished by
      piceatannol, a SYK inhibitor, suggesting that SYK play a significant role in AZA
      inducible invasion suppression. SYK promoter hypermethylation was found
      infrequent in pathologically normal mammary tissues or benign lesions (<5%). In
      contrast, SYK methylation was frequently identified in ductal carcinoma in situ (
      approximately 45%) and invasive ductal carcinoma (47% in node-negative and 40% in
      node-positive cases), indicating that the hypermethylation of SYK occurs at a
      stage prior to the development of invasion phenotypes. All these results
      suggested a potential use of SYK methylation as a valuable biomarker to detect
      early cancerous lesions and support the use of AZA as a new reagent to the
      management of advanced breast cancer.

PMID- 15455374
TI  - Combined therapy of experimental pancreatic cancer with CYP2B1 producing cells:
      low-dose ifosfamide and local tumor irradiation.
AB  - Local therapy of pancreatic cancer with microencapsulated CYP2B1-producing cells
      and ifosfamide showed an effect both on the primary tumor and on distant
      metastatases. This possibly represents a consequence of the activation of immune
      response. Other studies have demonstrated that local tumor irradiation leads to
      the activation of the intratumoral lymphocyte infiltration. The aim of our study
      was to investigate the efficacy of the combined therapy with low-dose
      irradiation, ifosfamide and CYP2B1-producing cells. Syngenic pancreatic cancer
      was induced in 38 Lewis-rats by subcutaneous inoculation of 1 x 10(6) (DSL6A)
      tumor cells. Microencapsulated CYP2B1-producing cells were injected peritumorally
      10--12 weeks after tumor implantation. Animals were randomized to the following
      groups: 1) control (NaCl, 1 ml i.p.), 2) ifosfamide (50 mg/kg, i.p., (3x/week),
      3) local irradiation with 5 Gy and 4) ifosfamide plus irradiation. The tumor
      growth was monitored for 3 weeks. The tumor infiltration with CD4+, CD8+, NK
      cells, microvessel density and proliferation rates were investigated by
      immunohistochemistry. Cytokine plasma level for TNF-alpha were measured by ELISA.
      Seven of 9 animals in the group of combined therapy showed an objective response
      to the therapy. The therapy with ifosfamide or radiation alone showed 5 and 3
      responders, respectively. The mean tumor volume was significantly reduced after
      combined ifosfamide plus radiation therapy in the first week, whereas monotherapy
      with ifosfamide or radiation significantly decreased tumor growth earliest after
      2 and 3 weeks, respectively. The high plasma level of TNF-alpha in the control
      group was significantly reduced after combined ifosfamide/irradiation treatment.
      The lymphocyte infiltration and tumor proliferation were not significantly
      different between the groups. Microvascular density was significantly increased
      after ifosfamide and ifosfamide plus irradiation therapy. The combination of
      ifosfamide/CYP2B1-producing cells and irradiation showed an earlier therapeutical
      effect on the growth of rat pancreatic cancer than the irradiation or ifosfamide
      alone. There was no evidence of late activation of lymphocyte infiltration and
      PCNA-positive tumor cells.

PMID- 15455375
TI  - Activation of gef-h1, a guanine nucleotide exchange factor for RhoA, by DNA
      transfection.
AB  - Several oncogenes isolated by the NIH/3T3 transformation assay, i.e., dbl, dbs,
      lbc, lfc, lsc, net, ost and tim, contain a Dbl homology (DH) and a pleckstrin
      homology (PH) domain and act as GEFs (guanine nucleotide exchange factors) for
      Rho-like GTPases. In a search for genes with oncogenic potential in DNA from the
      monocytic leukaemia cell line U937, we identified an amino-terminal truncated
      form of gef-h1, a gene encoding a GEF for RhoA. These data support the idea that
      a systematic search for mutations and/or deletions of GEFs in human cancer is
      promising.

PMID- 15455376
TI  - O6-methylguanine-DNA methyltransferase methylation and TP53 mutation in malignant
      astrocytomas and their relationships with clinical course.
AB  - Epigenetic silencing of O(6)-methylguanine-DNA methyltransferase (MGMT) by
      promoter methylation can confer cancer cells with an increased sensitivity to
      alkylating chemotherapeutic agents and a higher susceptibility to TP53 transition
      mutations. The aim of our study was to assess the correlation of promoter
      methylation of the MGMT gene with TP53 mutations and the clinical characteristics
      of malignant astrocytomas. We analyzed the MGMT promoter methylation and TP53
      mutations in 45 malignant astrocytomas (16 anaplastic astrocytomas and 29
      glioblastomas multiforme) treated prospectively with 1-(4-amino-2-methyl-5
      pyrimidinyl)methyl-3-2(2-chloroethyl)-3-nitrosourea, interferon-beta and
      radiation therapy, and evaluated their clinical usefulness. MGMT promoter
      methylation was found in 17 (38%) of the 45 newly diagnosed malignant
      astrocytomas. A clear trend existed between MGMT methylation and G:C to A:T
      transition mutations of TP53 (p = 0.0596). Patients with MGMT-methylated tumors
      displayed a greater chance of responding to adjuvant therapy as compared with
      those with MGMT-unmethylated tumors (p = 0.0393). TP53 mutation was not
      significantly associated with the clinical response (p = 0.1310). While neither
      MGMT methylation nor TP53 mutation had a significant effect on prognosis of the
      whole population, the presence of MGMT methylation emerged as a significant
      predictor of a longer survival when exclusively analyzing 29 patients with
      glioblastomas multiforme. These findings highlight the importance of MGMT
      methylation as a specific predictive factor for responsiveness to nitrosourea
      chemotherapy.

PMID- 15455377
TI  - Independent and combined effects of alcohol intake, tobacco smoking and betel
      quid chewing on the risk of esophageal cancer in Taiwan.
AB  - A multicenter case-control study was conducted in northern and southern Taiwan to
      clarify the independent and combined effects of alcohol intake, tobacco smoking
      and betel quid chewing on the risk of esophageal cancer. A total of 513 patients
      with newly diagnosed and histopathologically confirmed squamous cell carcinoma of
      the esophagus and 818 gender, age and study hospital-matched controls were
      included. We found a significant dose-response relationship between the duration
      and intensity of consumption of the 3 substances and the development of this
      neoplasm in this site. Although the amount of alcohol consumed had a stronger
      effect on the risk of esophageal cancer than the number of years it was consumed,
      however, the number of years one smoked had a stronger effect on the risk than
      the amount of cigarettes consumed. The strongest risk factor of esophageal cancer
      was alcohol intake, with highest risk (OR = 13.9) being for those who consumed
      more than 900 g/day-year. Combined exposure to any 2 of 3 substances brought the
      risks up to 8.8-19.7 fold and, to all 3 substances, to 41.2-fold. A
      multiplicative interaction effect for alcohol drinkers who smoked on cancer risk
      was detected, whereas an additive interaction effect was found among drinkers who
      chewed. The combined effect of all 3 substances accounted for 83.7% of the
      attributable fraction of contracting esophageal cancer in this population. In
      conclusion, these results suggest that the intensity and the length of time
      alcohol and tobacco are used play different roles in the etiology of esophageal
      cancer. Alcohol separately interacts with tobacco and betel quid in a differently
      synergistic way in determining the development of this site of cancer.

PMID- 15455378
TI  - Prospective study of risk factors for esophageal and gastric cancers in the
      Linxian general population trial cohort in China.
AB  - Esophageal cancer incidence and mortality rates in Linxian, China are among the
      highest in the world. We examined risk factors for esophageal squamous cell
      carcinoma (ESCC), gastric cardia cancer (GCC), and gastric noncardia cancer
      (GNCC) in a population-based, prospective study of 29,584 adults who participated
      in the Linxian General Population Trial. All study participants completed a
      baseline questionnaire that included questions on demographic characteristics,
      personal and family history of disease, and lifestyle factors. After 15 years of
      follow-up, a total of 3,410 incident upper gastrointestinal cancers were
      identified, including 1,958 ESCC, 1,089 GCC and 363 GNCC. Cox proportional hazard
      models were used to estimate risks. Increased age and a positive family history
      of esophageal cancer (including ESCC or GCC) were significantly associated with
      risk at all 3 cancer sites. Additional risk factors for ESCC included being born
      in Linxian, increased height, cigarette smoking and pipe smoking; for GCC, male
      gender, consumption of moldy breads and pipe smoking; and for GNCC, male gender
      and cigarette smoking. Protective factors for ESCC included formal education,
      water piped into the home, increased consumption of meat, eggs and fresh fruits
      and increased BMI; for GCC, formal education, water piped into the home,
      increased consumption of eggs and fresh fruits and alcohol consumption; and for
      GNCC, increased weight and BMI. General socioeconomic status (SES) is a common
      denominator in many of these factors and improving SES is a promising approach
      for reducing the tremendous burden of upper gastrointestinal cancers in Linxian.

PMID- 15455379
TI  - Polymorphisms in sulfotransferases SULT1A1 and SULT1A2 are not related to
      colorectal cancer.

PMID- 15455380
TI  - EGF signalling in prostate cancer cell lines is inhibited by a high expression
      level of the endocytosis protein REPS2.
AB  - In advanced prostate cancer, cellular changes occur leading to a transition from
      androgen-dependent to androgen-independent growth. During this transition,
      proliferation of androgen-dependent prostate cancer cells becomes more and more
      dependent on growth factors, like the epidermal growth factor (EGF). Endocytosis
      of growth factor receptors, one of the mechanisms that controls growth factor
      signalling, was observed to be markedly changed in advanced metastatic prostate
      cancer. Internalisation and signalling of EGF receptors was examined in different
      prostate cancer cell lines, in relation to the expression level of the
      endocytosis-related REPS2 gene. It was observed that a high level of REPS2
      correlates with reduced EGF-internalisation. To investigate this more thoroughly,
      prostate cancer cells with inducible REPS2 expression were generated. Using these
      cells, it was found that REPS2-induction indeed results in reduction of EGF
      internalisation. Furthermore, when EGF receptor signalling was evaluated, by
      examination of mRNA expression for several EGF-responsive genes (EGF receptor,
      EGR-1, Fos and Jun), it was observed that induced expression of REPS2 exerts an
      inhibiting effect on this signalling. From these experiments, it is concluded
      that increased REPS2 expression negatively affects EGF receptor internalisation
      and subsequent signalling. Therefore, decreased REPS2 expression during prostate
      cancer progression, observed in earlier work, may result in enhanced EGF receptor
      expression and signalling, which could add to the androgen-independent state of
      advanced prostate cancer.

PMID- 15455381
TI  - Hsp90 inhibitors deplete key anti-apoptotic proteins in pediatric solid tumor
      cells and demonstrate synergistic anticancer activity with cisplatin.
AB  - Drugs that inhibit the function of heat shock protein 90 (Hsp90) are of interest
      in the treatment of pediatric cancers because these agents deplete the cellular
      levels of signaling molecules that are important for the growth and survival of
      many childhood tumors. To generate preclinical data in anticipation of clinical
      trials of Hsp90 inhibitors in children, we evaluated the effects of the Hsp90
      inhibitor geldanamycin (GA) alone and in combination with cis-platinum (II)
      diamine dichloride (cisplatin) in pediatric tumor cells. Immunoblotting
      demonstrated depletion of the Hsp90 client proteins AKT and the type 1 insulin
      like growth factor receptor (IGF1R) in a panel of pediatric tumor cell lines
      after exposure to GA. Drug exposure also led to a dramatic decrease in cell
      survival/proliferation in MYCN-amplified and non-amplified neuroblastoma cells.
      Moderate inhibition of survival/proliferation was observed in RB-deficient and
      wild-type osteosarcoma cells. Treatment of neuroblastoma and osteosarcoma cell
      lines with GA in combination with cisplatin resulted in greater than additive
      inhibition of survival/proliferation based on median dose analysis. Exposure to
      this drug combination also resulted in a marked increase in nuclear fragmentation
      as assessed by terminal deoxynucleotide transferase-mediated UTP nick end
      labeling (TUNEL) analysis. Combined exposure also abrogated the ability of GA to
      induce a cytoprotective heat shock response and resulted in Hsp90 adduct
      formation. Our findings suggest that Hsp90 inhibitors may prove useful either
      alone or as a component of multi-drug regimens in the treatment of neuroblastoma
      and osteosarcoma.

PMID- 15455382
TI  - Differential expression of protease activated receptor 1 (Par1) and pY397FAK in
      benign and malignant human ovarian tissue samples.
AB  - Protease activated receptors (PAR) form a family of G-protein coupled receptors
      (GPCR) encoding their own ligands and uniquely activated via proteolytic
      cleavage. Although proteases in general have been implicated in the remodeling of
      the extracellular tumor microenvironment, the role of cell surface receptors
      activated by proteolysis is now emerging. In our present study we investigated
      the expression pattern of protease activated receptor 1 hPar1 in ovarian
      carcinoma tissue samples. Abundant hPar1 mRNA and protein were detected in "low
      malignant potential" and in invasive carcinomas, regardless of the histological
      subtype. In contrast, no hPar1 expression was detected on the cell surface of
      normal ovarian epithelium. The differential expression pattern of hPar1 was shown
      by in situ hybridization, immunohistochemistry and semi-quantitative RT-PCR
      analyses. In early stages of ovarian carcinoma (Ia), the contra lateral normal
      ovary showed strong PAR1 expression as opposed to the lack of expression in the
      ovarian epithelium obtained from normal individuals. In parallel, we analyzed the
      expression pattern of alphavbeta5 integrin and of activated focal adhesion kinase
      (FAK), a major focal contact protein, in these tissues. Although abundant
      expression of alphavbeta5 integrin was observed in all tissues specimens
      examined, regardless of either normal or malignant, the level of activated FAK
      was differentially expressed. Phosphorylated FAK was seen in invasive ovarian
      carcinoma, but not in the normal ovarian epithelium. The abundant hPar1 levels in
      pathological malignant ovarian carcinoma is likely to transmit signals leading to
      the phosphorylation of FAK and thereby alterations in the integrin functional
      state. Altogether our data suggest that hPar1 and FAK cooperate to promote
      ovarian cancer malignancy.

PMID- 15455383
TI  - Do nonattenders in mammography screening programmes seek mammography elsewhere?
AB  - The objectives of our study were to analyse the use of diagnostic mammography
      among nonattenders and attenders in organised mammography screening in Denmark in
      2000, to assess the contamination from organised screening of noninvited age
      groups and to measure the impact of local policy on opportunistic screening. Data
      on all diagnostic mammographies performed in Denmark in 2000 and data on women
      targeted by the 2 organised mammography screening programmes in Copenhagen and
      the county of Fyn were collected. All data were linked by the Danish personal
      identification number. Information on the official policy in 2000 with regard to
      opportunistic screening was collected from all counties. The proportion of women
      using diagnostic mammography was only 1-3% for both attenders and nonattenders in
      organised mammography screening, but it was significantly higher in Copenhagen
      than in Fyn, due to availability of mammography in private clinics. The
      proportion of women using diagnostic mammography varied from 1-4% across
      counties. The official policy on access to diagnostic mammography and
      contamination from organised mammography screening of adjacent age groups had no
      impact on the use. Instead, urbanisation was positively correlated with use of
      diagnostic mammography. In conclusion, our results clearly showed that
      nonattenders in organised mammography screening programmes do not seek
      mammography outside the programme. Since a positive policy toward opportunistic
      screening did not have any effect, our results add further evidence to existing
      knowledge that the only reasonable way to achieve high mammography coverage is
      through a well-organised screening programme.

PMID- 15455384
TI  - Sequence- and schedule-dependent enhancement of zoledronic acid induced apoptosis
      by doxorubicin in breast and prostate cancer cells.
AB  - We investigated whether the combination of zoledronic acid and doxorubicin
      induced apoptosis of breast and prostate cancer cell lines, and if synergistic
      interaction was present. We investigated whether the levels of cell death altered
      depending on the sequence in which the drugs were administered and the possible
      mechanism of action responsible for the increased cell death following combined
      treatments. Breast and prostate cancer cells were treated with zoledronic acid
      alone, doxorubicin alone, or drugs in sequence (doxorubicin before, after, or
      with zoledronic acid), and the levels of apoptotic death were determined by
      evaluation of nuclear morphology. We found that clinically relevant
      concentrations of doxorubicin and zoledronic acid induced sequence- and schedule
      dependent apoptosis of breast and prostate cancer cells. For maximal apoptosis,
      cells had to be pretreated for 24 hr with doxorubicin before immediate treatment
      with zoledronic acid for 1 hr. This observation is a characteristic feature of
      cell cycle phase-specific synergistic effect. Replacing zoledronic acid with the
      nonnitrogen-containing bisphosphonate clodronate did not induce increased
      apoptosis. Induction of apoptosis was mainly via inhibition of the mevalonate
      (MVA) pathway, as addition of the MVA pathway intermediary geranylgeraniol
      inhibited the induction of apoptosis by doxorubicin followed by zoledronic acid.
      In conclusion, combined treatment of breast and prostate cancer cell lines with
      clinically relevant doses of doxorubicin and zoledronic acid induces apoptosis in
      a synergistic fashion. These findings may have relevance for the clinical
      setting, particularly breast cancer patients receiving these drugs in the
      adjuvant setting.

PMID- 15455385
TI  - High throughput functional genomics: identification of novel genes with tumor
      suppressor phenotypes.
AB  - We have used a combination of high throughput functional genomics, computerized
      database mining and expression analyses to discover novel human tumor suppressor
      genes (TSGs). A genome-wide high throughput cDNA phenotype screen was established
      to identify genes that induce apoptosis or reduce cell viability. TSGs are
      expressed in normal tissue and frequently act by reduction of growth of
      transformed cells or induce apoptosis. In agreement with that and thus serving as
      platform validation, our pro-apoptotic hits included genes for which tumor
      suppressing activities were known, such as kangai1 and CD81 antigen. Additional
      genes that so far have been claimed as putative TSGs or associated with tumor
      inhibitory activities (prostate differentiation factor, hRAS-like suppressor 3,
      DPH2L1-like and the metastasis inhibitor Kiss1) were confirmed in their proposed
      TSG-like phenotype by functionally defining their growth inhibitory or pro
      apoptotic function towards cancer cells. Finally, novel genes were identified for
      which neither association with cell growth nor with apoptosis were previously
      described. A subset of these genes show characteristics of TSGs because they (i)
      reduce the growth or induce apoptosis in tumor cells; (ii) show reduced
      expression in tumor vs. normal tissue; and (iii) are located on chromosomal (LOH
      ) loci for which cancer-associated deletions are described. The pro-apoptotic
      phenotype and differential expression of these genes in normal and malignant
      tissue make them promising target candidates for the diagnosis and therapy of
      various tumors.

PMID- 15455386
TI  - Cervical carcinoma in Algiers, Algeria: human papillomavirus and lifestyle risk
      factors.
AB  - We conducted a hospital-based case-control study in Algiers, Algeria. A total of
      198 cervical carcinoma (CC) cases (including 15 adeno- and adenosquamous
      carcinomas) and 202 age-matched control women were included. Human papillomavirus
      (HPV) DNA in cervical cells was evaluated using a PCR assay. Odds ratios and
      corresponding confidence intervals were computed by means of unconditional
      multiple logistic regression models. HPV infection was detected in 97.7% of CC
      cases and 12.4% of control women (OR = 635). Nineteen different HPV types were
      found. HPV 16 was the most common type in both CC cases and control women,
      followed by HPV 18 and 45. Twelve types (HPV 16, 18, 31, 33, 35, 39, 45, 51, 52,
      56, 66 and 73) were found as single infections in CC cases. Multiple HPV
      infections did not show a higher odds ratio for CC than single infections. In
      addition to HPV infection, husband's extramarital sexual relationships with other
      women (OR = 4.8) or prostitutes (OR = 3.2), residing in a rural environment for
      most of one's life (OR = 4.9) and indicators of poor sanitation or poor hygiene
      were the strongest risk factors for CC. Oral contraceptive use was unrelated to
      CC risk, while multiparity emerged as a significant risk factor after adjustment
      for sexual habits. Intrauterine device users showed a lower CC risk than
      nonusers. The role of major risk factors, except inside toilet, was confirmed in
      the analysis restricted to HPV-positive women. The distribution of HPV types in
      CC cases and control women in Algeria is more similar to the one found in Europe
      than the one in sub-Saharan Africa, where HPV 16 is less prevalent. A vaccine
      against HPV 16 and 18 may be effective in more than 3/4 of CCs in Algeria.

PMID- 15455387
TI  - Lower levels of nuclear beta-catenin predict for a poorer prognosis in localized
      prostate cancer.
AB  - Beta-catenin in its role as a nuclear signaling molecule has been implicated in
      prostate carcinogenesis primarily through modulation of androgen receptor
      activity. We defined the pattern of beta-catenin protein expression in the nuclei
      of normal, hyperplastic and malignant human prostate tissue and determined
      whether differences in expression were associated with disease progression and
      prognosis. Five normal prostates, 26 benign prostatic hypertrophy specimens, 232
      radical prostatectomy specimens from patients with clinically localized prostate
      cancer (PC) and 20 cases of advanced PC were assessed for beta-catenin expression
      using immunohistochemistry. Nuclear beta-catenin expression in localized PC was
      significantly lower than that in benign prostate tissue (p < 0.001) and
      significantly higher than that in advanced PC tissue (p < 0.001). In addition,
      lower levels of nuclear beta-catenin expression (< 10% of cancer cells) predicted
      for a shorter biochemical relapse-free survival in patients with localized PC (p
      = 0.008) and were inversely correlated with preoperative prostate-specific
      antigen (PSA) levels (p = 0.01). Analysis of the low-risk subgroup of patients
      with preoperative PSA levels < 10 ng/ml demonstrated that lower levels of nuclear
      beta-catenin expression (< 10% of cancer cells) again predicted for a poorer
      prognosis (p = 0.006). In conclusion, lower levels of nuclear beta-catenin
      expression are found in malignant compared to benign prostate tissue. In
      addition, lower nuclear beta-catenin expression is associated with a poorer
      prognosis in localized PC, in particular, in the low-risk subgroup of patients
      with preoperative PSA levels < 10 ng/ml. Thus, the level of nuclear beta-catenin
      expression may be of clinical utility as a preoperative prognostic marker in low
      risk localized PC.

PMID- 15455388
TI  - C-Met overexpression in node-positive breast cancer identifies patients with poor
      clinical outcome independent of Her2/neu.
AB  - Receptor tyrosine kinases play an important role in malignant transformation of
      epithelial cells by activating signal transduction pathways important for
      proliferation, invasion and metastasis. In a pilot study (n = 40), we evaluated
      expression of the c-Met and Her2/neu receptor tyrosine kinases and the c-Met
      ligand hepatocyte growth factor/scatter factor (HGF/SF) in primary breast cancers
      and their lymph node metastases using both conventional immunohistochemistry and
      confocal immunofluorescence. Neither c-Met and HGF/SF nor Her2/neu expression
      correlated with established prognostic factors such as age, lymph node
      involvement, estrogen receptor (ER), progesterone receptor (PR), tumor size, or
      grade. Both staining methods confirmed a significant correlation between c-Met
      overexpression and a high risk of disease progression. Furthermore, among tumors
      with c-Met overexpression, only 50% also overexpress Her2/neu, thus identifying a
      subset of patients with aggressive disease in addition to Her2/neu. Median
      disease-free survival in patients with c-Met overexpressing tumors was 8 months
      compared to 53 months when c-Met expression was low (p = 0.037; RR = 3.0). This
      significant impact of c-Met on tumor aggressiveness independent of Her2/neu was
      also confirmed by multivariate analysis. In conclusion, the role of c-Met
      expression as a prognostic variable and consequently as an interesting target for
      novel therapeutic approaches deserves further analysis in a larger cohort of
      patients.

PMID- 15455389
TI  - Frequent p16INK4a promoter hypermethylation in human papillomavirus-infected
      female lung cancer in Taiwan.
AB  - Inactivation of p16INK4a gene through promoter hypermethylation has been
      frequently observed in non small cell lung cancer; however, various studies have
      shown a controversial correlation between p16INK4a hypermethylation and cigarette
      smoking. Our recent report showed that human papillomarvirus (HPV) 16/18
      infections were associated with the development of nonsmoking female lung cancer
      in Taiwan and we further speculated that HPV infection may be linked with
      p16INK4a hypermethylation. To verify the influence of environmental exposure,
      including cigarette smoking, environmental carcinogen exposure and HPV infections
      on p16INK4a hypermethylation, tumors from 162 lung patients, including 67 smoking
      males, 41 nonsmoking males and 58 nonsmoking females, were subjected to p16INK4a
      hypermethylation analysis by methylation-specific PCR. As the results showed,
      p16INK4a hypermethylation was detected in 40 (59.7%) of 67 smoking male, 15
      (36.6%) of 41 nonsmoking male and 35 (60.3%) of 58 nonsmoking female lung tumors.
      This result seemed to reveal that gender and cigarette smoking both possess an
      equal influence on p16INK4a hypermethylation. This result also led to a
      speculation that HPV infection may promote p16INK4a hypermethylation in
      nonsmoking female lung cancer patients. From our data, p16INK4a hypermethylation
      frequency in nonsmoking female lung tumors with HPV infection was as high as 70%
      (30 of 43) compared to those without HPV infection (33%; 5 of 15). In fact, the
      correlation between HPV infection and p16INK4a hypermethylation was only observed
      in nonsmoking female lung tumors (p = 0.017), but not in smoking male or
      nonsmoking male lung tumors. Moreover, the reverse correlation between p16INK4a
      immunostaining and p16INK4a promoter hypermethylation was also only observed in
      nonsmoking female lung tumors. These results strongly suggested that the
      involvement of HPV infection in lung tumorigenesis of nonsmoking female cancer
      patients in Taiwan may be mediated at least in part through the increase of
      hypermethylation to cause p16INK4a inactivation.

PMID- 15455390
TI  - Increased endothelial uptake of paclitaxel as a potential mechanism for its
      antiangiogenic effects: potentiation by Cox-2 inhibition.
AB  - Paclitaxel has antiangiogenic properties, but the mechanisms for the enhanced
      sensitivity of endothelial cells (ECs) to this drug are not established. The aims
      of our study were to compare the distribution of paclitaxel into ECs with other
      cell types, to assess the effects of low doses of paclitaxel on Cox-2 expression
      and to determine the combined effects of paclitaxel and Cox-2 inhibitors on
      angiogenesis in vitro and in patients with cancer. Upon exposure to low (5 nM)
      concentrations of [3H]-paclitaxel, uptake of radioactivity was more than 5 times
      higher in ECs than other cell types. Exposing human umbilical vein ECs to low
      nanomolar (1-50 nM) concentrations of paclitaxel enhanced Cox-2 expression more
      than 2-fold, as measured by ELISA. Combined treatment with paclitaxel and the Cox
      2 inhibitor NS-398 resulted in increased antiendothelial effects as compared to
      each agent alone. To assess the biologic effects of the combined treatment in
      vivo, 4 cancer patients were treated with a prolonged intravenous infusion of
      paclitaxel (10 mg/m2/day) and the Cox-2 inhibitor celecoxib (400 mg p.o. BID),
      and plasma angiogenic activity and drug levels were measured. The treatment was
      well tolerated, providing steady-state concentrations of paclitaxel in plasma
      near 10 nM and potent plasma antiendothelial effects were observed. These
      findings suggest that antiangiogenic effects of paclitaxel may be due its
      preferential accumulation in ECs. Low dose paclitaxel in combination with a Cox-2
      inhibitor is an attractive antiangiogenic and antitumor strategy that deserves
      further evaluation in clinical trials.

PMID- 15455391
TI  - Silencing of the retinoid response gene TIG1 by promoter hypermethylation in
      nasopharyngeal carcinoma.
AB  - Tazarotene-induced gene 1 (TIG1) and Tazarotene-induced gene 3 (TIG3) are
      retinoid acid (RA) target genes as well as candidate tumor suppressor genes in
      human cancers. In our study, we have investigated the expression of TIG1 and TIG3
      in nasopharyngeal carcinoma (NPC). Loss of TIG1 expression was found in 80% of
      NPC cell lines and 33% of xenografts, whereas TIG3 was expressed in all NPC
      samples and immortalized nasopharyngeal epithelial cells. In order to elucidate
      the epigenetic silencing of TIG1 in NPC, the methylation status of TIG1 promoter
      was examined by genomic bisulfite sequencing and methylation-specific PCR (MSP).
      We have detected dense methylation of TIG1 5'CpG island in the 5 TIG1-negative
      NPC cell lines and xenograft (C666-1, CNE1, CNE2, HONE1 and X666). Partial
      methylation was observed in 1 NPC cell line HK1 showing dramatic decreased in
      TIG1 expression. Promoter methylation was absent in 2 TIG1-expressed NPC
      xenografts and the normal epithelial cells. Restoration of TIG1 expression and
      unmethylated alleles were observed in NPC cell lines after 5-aza-2'-deoxycytidine
      treatment. Moreover, the methylated TIG1 sequence was detected in 39 of 43
      (90.7%) primary NPC tumors by MSP. In conclusion, our results showed that TIG1
      expression is lost in the majority of NPC cell lines and xenografts, while
      promoter hypermethylation is the major mechanism for TIG1 silencing. Furthermore,
      the frequent epigenetic inactivation of TIG1 in primary NPC tumors implied that
      it may play an important role in NPC tumorigenesis.

PMID- 15455392
TI  - Is the proportion of infection-related cancers much greater than generally
      appreciated?

PMID- 15455393
TI  - Disturbed surround inhibition in focal hand dystonia.
AB  - Disturbances in surround inhibition could account for various movement disorders.
      Here we test the functional operation of surround inhibition in focal hand
      dystonia. Transcranial magnetic stimulation was set to be triggered by self
      initiated voluntary flexion of the index finger. During this movement, motor
      evoked potential amplitudes from the little finger muscle were significantly
      suppressed in healthy subjects but enhanced in dystonia patients. This result
      supports the idea that disturbed surround inhibition is a principal
      pathophysiological mechanism of dystonia.

PMID- 15455394
TI  - alpha-Synuclein promoter confers susceptibility to Parkinson's disease.
AB  - Familial Parkinson's disease (PD) has been linked to missense and genomic
      multiplication mutations of the alpha-synuclein gene (SNCA). Genetic variability
      within SNCA has been implicated in idiopathic PD in many populations. We now
      confirm and extend these findings, within a Belgian sample, using a high
      resolution map of genetic markers across the SNCA locus. Our study implicates the
      SNCA promoter in susceptibility to PD, and more specifically defines a minimum
      promoter haplotype, spanning approximately 15.3kb of sequence, which is
      overrepresented in patients. Our findings represent a biomarker for PD and may
      have implications for patient diagnosis, longitudinal evaluation, and treatment.

PMID- 15455395
TI  - Diabetes underlies common neurological disorders.

PMID- 15455396
TI  - A novel locus for pure recessive hereditary spastic paraplegia maps to 10q22.1
      10q24.1.
AB  - The hereditary spastic paraplegias (HSPs) are a group of clinically and
      genetically heterogeneous disorders characterized by progressive lower-limb
      spasticity. In this study, we performed linkage analysis on an autosomal
      recessive pure HSP family and mapped the disease to chromosome 10q22.1-10q24.1, a
      locus partially overlapping the existing SPG9 locus. We have either identified a
      novel locus for pure recessive HSP (SPG27), or we have found the first case of
      allelic disorders with different mode of inheritance in HSP. If the disorders are
      indeed allelic, our results have reduced the SPG9 interval by 3Mb with D10S536
      and D10S1758 as flanking markers.

PMID- 15455397
TI  - A mutation in the HSN2 gene causes sensory neuropathy type II in a Lebanese
      family.
AB  - Hereditary sensory and autonomic neuropathy (HSAN) type II is an autosomal
      recessive disorder clinically characterized by distal and proximal sensory loss
      that is caused by the reduction or absence of peripheral sensory nerves.
      Recently, a novel gene called HSN2 has been found to be the cause of HSAN type II
      in five families from Newfoundland and Quebec. Screening of this gene in an HSAN
      type II Lebanese family showed a 1bp deletion mutation found in a homozygous
      state in all affected individuals. This novel mutation supports the hypothesis
      that HSN2 is the causative gene for HSAN type II.

PMID- 15455398
TI  - Insulin signaling pathways in cortical dysplasia and TSC-tubers: tissue
      microarray analysis.
AB  - To evaluate the possible roles of the Akt/PKB-mTOR-p70S6K-S6 and cap-dependent
      translation (eIF4G) pathways in the pathogenesis of tuberous sclerosis complex
      (TSC)-associated cortical tubers and focal cortical dysplasia (FCD), we performed
      qualitative and semiquantitative immunohistochemical evaluation on surgically
      resected corticectomy specimens to detect phosphorylated molecules as activated
      downstream targets of the signaling pathways. A tissue microarray paraffin block
      was constructed from 63 archival specimens of surgically resected TSC tubers,
      FCDs with balloon cells, cortical dysplasia without balloon cells, and
      histologically normal-appearing neocortex obtained from cases with Rasmussen
      encephalitis, cystic-gliotic encephalopathy, and temporal lobe epilepsy. Abnormal
      neuroglial cells were positive for phospho-S6 and phospho-eIF4G with various
      staining intensities in FCDs and TSC tubers. Both proteins were much less
      abundantly expressed in normal-appearing neocortex. Phospho-mTOR expression was
      observed in neurons in all groups. The expression of phospho-S6 and phospho-eIF4G
      was associated with dysplastic lesions (p < 0.05), and the cytoplasmic phospho
      p70S6K expression was most specific for and abundant in TSC tubers and much less
      prominent in other groups (p < 0.01). These results suggest that constitutive
      activation of cytoplasmic p70S6K plays a pivotal role in the pathogenesis of TSC
      tubers and that FCDs possess a distinct mechanism for activation of S6 and eIF4G.

PMID- 15455399
TI  - Reduction of cortical TrkA but not p75(NTR) protein in early-stage Alzheimer's
      disease.
AB  - Degeneration of cholinergic nucleus basalis (NB) cortical projection neurons is
      associated with cognitive decline in late-stage Alzheimer's disease (AD). NB
      neuron survival is dependent on coexpression of the nerve growth factor (NGF)
      receptors p75(NTR) and TrkA, which bind NGF in cortical projection sites. We have
      shown previously a significant reduction of NB perikarya expressing p75(NTR) and
      TrkA protein during the early stages of AD. Whether there is a concomitant
      reduction in cortical levels of these receptors during the progression of AD is
      unknown. p75(NTR) and TrkA protein was evaluated by quantitative immunoblotting
      in five cortical regions (anterior cingulate, superior frontal, superior
      temporal, inferior parietal, and visual cortex) of individuals clinically
      diagnosed with no cognitive impairment (NCI), mild cognitive impairment (MCI),
      mild/moderate AD, or severe AD. Cortical p75(NTR) levels were stable across the
      diagnostic groups. In contrast, TrkA levels were reduced approximately 50% in
      mild/moderate and severe AD compared with NCI and MCI in all regions except
      visual cortex. Mini-Mental Status Examination scores correlated with TrkA levels
      in anterior cingulate, superior frontal, and superior temporal cortex. The
      selective reduction of cortical TrkA levels relative to p75(NTR) may have
      important consequences for cholinergic NB function during the transition from MCI
      to AD.

PMID- 15455400
TI  - The acute effects of glycemic control on axonal excitability in human diabetics.
AB  - In diabetic nerves, the activation of the polyol pathway and a resulting decrease
      in Na(+)-K(+) ATPase activity lead to intra-axonal Na(+) accumulation and a
      smaller Na(+) gradient across the axolemma than normal. To investigate whether
      glycemic control is associated with acutely reversible changes in axonal
      excitability and Na(+) conductance, we measured the multiple excitability indices
      (strength-duration time constant, rheobase, refractoriness, and refractory
      period) of the median motor axons of 21 diabetic patients before and after
      intensive insulin treatment. Within 4 weeks after treatment was begun, there was
      a significant improvement in nerve conduction velocities, associated with
      increased strength-duration time constant, decreased rheobase, increased
      refractoriness, and prolonged refractory periods. Assuming that the strength
      duration time constant partly reflects persistent Na(+) conductance, and that
      refractoriness/refractory periods depend on inactivation of transient Na(+)
      channels caused by prior depolarization (the influx of Na(+)), the patterns of
      changes in these indices may reflect a reduced trans-axonal Na(+) gradient during
      hyperglycemia and its restoration by glycemic control in diabetic patients.
      Measurement of the excitability indices could provide new insights into the
      pathophysiology of human diabetic neuropathy.

PMID- 15455401
TI  - Pulse-synchronous eye oscillations revealing bone superior canal dehiscence.
AB  - Superior canal dehiscence syndrome is a newly recognized syndrome characterized
      by vertigo and nystagmus induced by sound (Tullio phenomenon) or changes of
      middle ear (Hennebert sign) or intracranial pressure. We report on a patient with
      bilateral superior canal dehiscence syndrome who presented with unusual
      manifestations including pulse-synchronous vertical pendular nystagmus and
      Valsalva-induced, up and counterclockwise-beating jerk nystagmus. These unusual
      symptoms may be a clue to a better understanding of the pathophysiology of
      superior canal dehiscence syndrome. Abnormal communication between the inner ears
      and the intracranial space may explain the vertical pendular and pulse
      synchronous nystagmus, modulated by increased intracranial pressure.

PMID- 15455402
TI  - Cytochrome c oxidase biogenesis in a patient with a mutation in COX10 gene.
AB  - We report a cytochrome c oxidase (COX)-deficient patient, clinically affected
      with Leigh-like disease, with a homozygous mutation in the COX10 start codon. Two
      dimensional gel electrophoresis showed a decrease of fully assembled COX without
      the accumulation of partially assembled COX subcomplexes. Western blot analysis
      with antibodies directed to COX subunits I, II, and IV showed a decrease of these
      subunits in this patient compared with control. Overexpression of the COX10
      protein in the patient's fibroblasts proved that the detected mutation was indeed
      the disease cause.

PMID- 15455403
TI  - Familial aggregation of Parkinson's disease: The Mayo Clinic family study.
AB  - Data on the familial aggregation of Parkinson's disease (PD) remain conflicting.
      We conducted a historical cohort study of 1,001 first-degree relatives of 162
      probands with PD and of 851 relatives of 147 control probands representative of
      the population of Olmsted County, Minnesota (from 1976 through 1995). In
      addition, we studied 2,713 first-degree relatives of 411 probands with PD
      referred to the Mayo Clinic from 1996 through 2000 and 625 spouses of PD or
      control probands. Whenever possible, relatives were interviewed and screened for
      parkinsonism either directly or through a proxy, and those who screened positive
      were examined or a copy of their medical record was obtained to confirm the
      diagnosis (family study method). Thirty relatives of population-based PD
      probands, 18 relatives of population-based control probands, 65 relatives of
      referral PD probands, and 8 spouses had developed PD. Combining population-based
      with referral PD probands and population-based control probands with spouses, the
      relative risk was modestly increased (relative risk, 1.71; 95% confidence
      interval, 1.11-2.64). Relatives of probands with younger onset (</=66 years;
      first tertile) had a more significantly increased risk (relative risk, 2.62; 95%
      confidence interval, 1.66-4.15), whereas relatives of probands with later onset
      had no increased risk. The relative risk decreased when the incidence of all
      types of parkinsonism was considered.

PMID- 15455404
TI  - Brainstem pathology in DYT1 primary torsion dystonia.
AB  - DYT1 dystonia is a severe form of young-onset dystonia caused by a mutation in
      the gene that encodes for the protein torsinA, which is thought to play a role in
      protein transport and degradation. We describe, for the first time to our
      knowledge, perinuclear inclusion bodies in the midbrain reticular formation and
      periaqueductal gray in four clinically documented and genetically confirmed DYT1
      patients but not in controls. The inclusions were located within cholinergic and
      other neurons in the pedunculopontine nucleus, cuneiform nucleus, and griseum
      centrale mesencephali and stained positively for ubiquitin, torsinA, and the
      nuclear envelope protein lamin A/C. No evidence of inclusion body formation was
      detected in the substantia nigra pars compacta, striatum, hippocampus, or
      selected regions of the cerebral cortex. We also noted tau/ubiquitin
      immunoreactive aggregates in pigmented neurons of the substantia nigra pars
      compacta and locus coeruleus in all four DYT1 dystonia cases, but not in
      controls. This study supports the notion that DYT1 dystonia is associated with
      impaired protein handling and the nuclear envelope. The role of the
      pedunculopontine and cuneiform nuclei, and related brainstem brainstem
      structures, in mediating motor activity and controlling muscle tone suggests that
      alterations in these structures could underlie the pathophysiology of DYT1
      dystonia [corrected]

PMID- 15455405
TI  - mTOR cascade activation distinguishes tubers from focal cortical dysplasia.
AB  - Balloon cells (BCs) in focal cortical dysplasia (FCD) and giant cells (GCs) in
      tubers of the tuberous sclerosis complex (TSC) share phenotypic similarities.
      TSC1 or TSC2 gene mutations in TSC lead to mTOR pathway activation and
      p70S6kinase (phospho-S6K) and ribosomal S6 (phospho-S6) protein phosphorylation.
      Phospho-S6K, phospho-S6, and phospho-S6K-activated proteins phospho-STAT3 and
      phospho-4EBP1 were detected immunohistochemically in GCs, whereas only phospho-S6
      was observed in BCs. Expression of four candidate gene families (cell signaling,
      cell adhesion, growth factor/receptor, and transcription factor mRNAs) was
      assayed in single, microdissected phospho-S6-immunolabeled BCs and GCs as a
      strategy to define whether BCs and GCs exhibit differential transcriptional
      profiles. Among 60 genes, differential expression of 24 mRNAs distinguished BCs
      from GCs and only 4 genes showed similar expression profiles between BCs and GCs.
      Tuberin mRNA levels were reduced in GCs from TSC patients with TSC2 gene
      mutations but were unchanged in BCs. Phospho-S6K, -S6, -STAT3, and -4EBP1
      expression in GCs reflects loss of hamartin-tuberin-mediated mTOR pathway
      inhibition. Phospho-S6 expression alone in BCs does not support mTOR cascade
      activation in FCD. Differential gene expression profiles in BCs and GCs supports
      the hypothesis that these cell types derive by distinct pathogenic mechanisms.

PMID- 15455406
TI  - Subcutaneous octreotide in cluster headache: randomized placebo-controlled double
      blind crossover study.
AB  - Current practical evidence-based acute treatments of cluster headache are limited
      to subcutaneous and intranasal formulations of sumatriptan, and oxygen. Two small
      randomized, double-blind trials suggested efficacy of somatostatin in cluster
      headache. We sought to determine whether octreotide, a somatostatin analog, is
      effective in the abortive treatment of acute cluster headache. Patients with
      episodic and chronic cluster headache, as defined by the International Headache
      Society, were recruited to a double-blind placebo-controlled crossover study.
      Patients were instructed to treat two attacks of at least moderate pain severity,
      with at least a 24-hour break, using subcutaneous octreotide microg or matching
      placebo. The primary end point was the headache response defined as very severe,
      severe, or moderate pain becomes mild or nil, at 30 minutes. The primary end
      point was examined using a multilevel analysis approach. A total of 57 patients
      were recruited of whom 46 provided efficacy data on attacks treated with
      octreotide and 45 with placebo. The headache response rate with subcutaneous
      octreotide was 52%, whereas that with placebo was 36%. Modeling the treatment
      outcome as a binomial where response was determined by treatment, using the
      patient as the level 2 variable, and considering period effect, sex, and cluster
      headache type as other variables of interest, we found that the effect of
      subcutaneous octreotide 100 microg was significantly superior to placebo (p <
      0.01). Subcutaneous octreotide 100 microg is effective in the acute treatment of
      cluster headache when compared with placebo. Nonvasconstrictor treatment of acute
      cluster headache is possible.

PMID- 15455409
TI  - Leflunomide protects from T-cell-mediated liver injury in mice through inhibition
      of nuclear factor kappaB.
AB  - Leflunomide is a novel immunosuppressive and anti-inflammatory agent for the
      treatment of autoimmune disease. The aim of this study was to investigate whether
      leflunomide protects from liver injury induced by concanavalin A (Con A), a T
      cell-dependent model of liver damage. BALB/c mice were injected with 25 mg/kg Con
      A in the presence or absence of 30 mg/kg leflunomide. Liver injury was assessed
      biochemically and histologically. Levels of circulating cytokines and expressions
      of cytokine messenger RNA (mRNA) in the liver and the spleen were determined.
      Treatment with leflunomide markedly reduced serum transaminase activities and the
      numbers of dead liver cells. Leflunomide significantly inhibited increases in
      plasma tumor necrosis factor alpha (TNF-alpha) and interleukin 2 concentrations,
      and also reduced TNF-alpha mRNA expression in the liver after administration of
      Con A. These findings were supported by the results in which leflunomide
      administration decreased the number of T lymphocytes infiltrating the liver as
      well as inhibiting their production of TNF-alpha. Activation of nuclear factor
      kappaB (NF-kappaB), which regulates TNF-alpha production, was inhibited in the
      liver of mice treated with leflunomide, resulting in a reduction of TNF-alpha
      production from lymphocytes infiltrating the liver. In conclusion, leflunomide is
      capable of regulating T-cell-mediated liver injury in vivo and that this event
      may depend on the decrease of TNF-alpha production in the liver through
      inhibition of NF-kappaB activation caused by leflunomide.

PMID- 15455410
TI  - Histone H2AX phosphorylation induced by selective photolysis of BrdU-labeled DNA
      with UV light: relation to cell cycle phase.
AB  - BACKGROUND: The induction of DNA double-strand breaks (DSBs) in chromatin
      triggers histone H2AX phosphorylation (on Ser-139) by ATM-, ATR-, or DNA
      dependent protein kinases (DNA-PK). Phosphorylated H2AX, denoted as gammaH2AX,
      can be detected immunocytochemically using an antibody that is specific to the
      Ser-139-phosphorylated epitope. We previously reported that the induction DSBs by
      DNA topoisomerase I or II inhibitors can be monitored in individual cells by
      measuring gammaH2AX immunofluorescence (IF) by cytometry. The present study
      explored whether the detection of gammaH2AX IF can serve as a marker of the
      presence of the DNA precursor bromodeoxyuridine (BrdU) that is incorporated into
      DNA. METHODS: HeLa cells growing on microscope slides were incubated with BrdU
      for 1 h, rinsed free of the precursor, and incubated for different periods for up
      to 12 h. The cells were then briefly incubated with Hoechst 33342 (to sensitize
      BrdU-labeled DNA to ultraviolet [UV] light), irradiated with 300 nm UV light to
      photolyze BrdU-labeled DNA, transferred back into culture for an additional hour,
      and fixed. Cells were concurrently immunostained for gammaH2AX (Alexa Fluor 633)
      and cyclin A (fluorescein isothiocyanate); their DNA was counterstained with 4,6
      diamidino-2-phenylindole. The intensities of cellular far red (gammaH2AX), green
      (cyclin A), and blue (DNA) fluorescences were measured by laser scanning
      cytometry. RESULTS: After a 1-h pulse of BrdU followed by exposure to UV, nearly
      all cells with S-phase DNA content had many-fold higher gammaH2AX IF than G(1) or
      G(2)/M cells. The nonirradiated cells had minimal ("programmed") expression of
      gammaH2AX, whereas the irradiated cells incubated without BrdU had uniformly
      elevated levels of gammaH2AX IF independent of the cell cycle phase. Pulse-chase
      experiments showed that the cohort of BrdU-labeled (gammaH2AX-positive) cells
      progressed through G(2)/M and into G(1) phase after 8 and 12 h of growth in BrdU
      free medium, respectively. Bivariate analysis of gammaH2AX versus cyclin A
      expression for the gated S-phase cells showed a correlation between these
      variables, suggesting that the rate of BrdU incorporation (DNA replication)
      correlates with expression of cyclin A. CONCLUSIONS: Photolysis of BrdU-labeled
      DNA induces DSBs and leads to H2AX phosphorylation. Detection of gammaH2AX IF
      indicates the presence of the incorporated BrdU, is compatible with concurrent
      detection of other intracellular antigens, and can be used to demonstrate cell
      cycle kinetics.

PMID- 15455411
TI  - FDA/PI flow cytometry assay of complement-mediated cytotoxicity of antibodies
      generated during xenotransplantation.
AB  - BACKGROUND: A flow cytometry complement-mediated cytotoxicity assay (FCCA) using
      fluorescein diacetate (FDA) and propidium iodide (PI) to measure antibody
      dependent toxicity is useful to determine the success of xenotransplant organs.
      We evaluated the validity of different mathematical models as a measure of
      cytotoxicity in FCCA. METHODS: Sera from untreated baboons (n = 7) and from
      immunosuppressed animals (n = 5) undergoing different xenotransplantation
      protocols with pig organs were tested by endogenous FCCA and a similar assay also
      using exogenous complement, and the results were compared with those of a
      complement-dependent hemolytic assay to detect anti-pig antibodies (APHA). The
      influence of PI/FDA staining and the use of several mathematical models were
      analyzed. RESULTS: For both groups of animals, we observed high correlations
      between the endogenous and exogenous FCCA pathways and between calculations based
      on PI and FDA staining. Of the four mathematical models tested--the Von Krogh
      equation, two exponential models, and area under the curve--the Von Krogh
      equation was the most appropriate in terms of goodness of fit and concordance
      with APHA. CONCLUSIONS: FDA/PI FCCA is useful to measure endogenous and exogenous
      complement-mediated cytotoxicities, and it has advantages related to
      identification of potential new xenoantibodies. Although all four mathematical
      models produced acceptable solutions, the Von Krogh equation was the best option.

PMID- 15455412
TI  - CytometryML.

PMID- 15455413
TI  - Stereodynamic effects in the adsorption of ethylene onto a metal surface.

PMID- 15455414
TI  - Tunable, superhydrophobically stable polymeric surfaces by electrospinning.

PMID- 15455415
TI  - Activation of an autoregulated protein kinase by conditional protein splicing.

PMID- 15455416
TI  - Difluoromethyl phenyl sulfone, a difluoromethylidene equivalent: use in the
      synthesis of 1,1-difluoro-1-alkenes.

PMID- 15455417
TI  - Single-crystal hexagonal disks and rings of ZnO: low-temperature, large-scale
      synthesis and growth mechanism.

PMID- 15455418
TI  - Creation of intestine-like interior space for metal-oxide nanostructures with a
      quasi-reverse emulsion.

PMID- 15455419
TI  - Inner core structure responds to communication between nanocapsule walls.

PMID- 15455420
TI  - Linear finite "mers"--homoleptic polynuclear heavy alkaline Earth metal
      pyrazolates.

PMID- 15455421
TI  - Sensing the critical point of high-pressure mixtures.

PMID- 15455422
TI  - Hydrogen-bonded banana liquid crystals.

PMID- 15455423
TI  - The [NH3Cl]+ ion.

PMID- 15455424
TI  - Development of a ruthenium-catalyzed asymmetric epoxidation procedure with
      hydrogen peroxide as the oxidant.

PMID- 15455425
TI  - An amphotericin B-fluorescein conjugate as a powerful probe for biochemical
      studies of the membrane.

PMID- 15455426
TI  - T-shaped nets of antimony atoms in the binary antimonide Hf5SB9.

PMID- 15455427
TI  - Three-dimensional structure of large-pore mesoporous cubic Ia3d silica with
      complementary pores and its carbon replica by electron crystallography.

PMID- 15455428
TI  - Functionalized carbon nanotubes for plasmid DNA gene delivery.

PMID- 15455429
TI  - A covalent-chemistry approach to giant macromolecules and their wetting behavior
      on solid substrates.

PMID- 15455430
TI  - Nanofibers from functionalized dendritic molecules.

PMID- 15455431
TI  - The magnetic mobius strip: synthesis, structure, and magnetic studies of odd
      numbered antiferromagnetically coupled wheels.

PMID- 15455432
TI  - Iterative one-pot synthesis of oligosaccharides.

PMID- 15455433
TI  - A five-coordinate homoleptic organotitanium(III) compound.

PMID- 15455434
TI  - Evidence for the formation of an iodosylbenzene(salen)iron active intermediate in
      a (salen)iron(III)-catalyzed asymmetric sulfide oxidation.

PMID- 15455435
TI  - A molecular multiproperty switching array based on the redox behavior of a
      ferrocenyl polychlorotriphenylmethyl radical.

PMID- 15455436
TI  - Spin trapping of 13C-labeled p-benzynes generated by Masamune-Bergman cyclization
      of bicyclic nine-membered enediynes.

PMID- 15455437
TI  - In the golden age of organocatalysis.
AB  - The term "organocatalysis" describes the acceleration of chemical reactions
      through the addition of a substoichiometric quantity of an organic compound. The
      interest in this field has increased spectacularly in the last few years as
      result of both the novelty of the concept and, more importantly, the fact that
      the efficiency and selectivity of many organocatalytic reactions meet the
      standards of established organic reactions. Organocatalytic reactions are
      becoming powerful tools in the construction of complex molecular skeletons. The
      diverse examples show that in recent years organocatalysis has developed within
      organic chemistry into its own subdiscipline, whose "Golden Age" has already
      dawned.

PMID- 15455439
TI  - A novel RAB7 mutation associated with ulcero-mutilating neuropathy.
AB  - There are two known autosomal dominant genes for the hereditary ulcero-mutilating
      neuropathies: SPTLC1 (hereditary sensory neuropathy type 1) and RAB7 (Charcot
      Marie-Tooth disease type 2B). We report a family with autosomal dominant ulcero
      mutilating neuropathy, developing in the teens and characterized by ulcers,
      amputations, sensory involvement in the feet but no motor features. Sequencing
      the RAB7 gene showed a novel heterozygous A to C mutation, changing asparagine to
      threonine at codon 161. The mutation is situated adjacent to a previously
      identified valine to methionine mutation at codon 162, implying a hotspot for
      mutations in the highly conserved C terminus of RAB7.

PMID- 15455441
TI  - Rapid eye movement sleep behavior disorder in parkinsonism with parkin mutations.
AB  - Rapid eye movement sleep behavior disorder (RBD) in the setting of parkinsonism
      or dementia often reflects an underlying synucleinopathy. Lewy bodies,
      intraneuronal aggregates containing abnormal alpha-synuclein, are absent in most
      cases of parkinsonism with parkin mutations (Park2). We performed clinical
      history and video-polysomnography in 10 Park2 patients (seven men; age, 51.2 +/-
      11.6 years; parkinsonism duration, 18.3 +/- 11.2 years) and found RBD in 6. In
      all instances, RBD followed the onset of motor symptoms by several years. Our
      study shows that RBD is frequent in Park2, suggesting that mechanisms other than
      synuclein deposition can cause RBD in neurodegenerative disorders.

PMID- 15455442
TI  - Dementia in dementia with Lewy bodies may not be attributable to Alzheimer
      pathology.

PMID- 15455443
TI  - Chiral effect on a self-assembling bicopper complex.
AB  - A bicopper complex was prepared with chiral ligands. The self-assembly of the
      complex in trans-decalin differed greatly for the racemic and nonracemic ligands.
      With the latter the resulting gel formed at a lower concentration and exhibited a
      higher thermal transition temperature. A large optical activity was found in the
      nonracemic bicopper complex, which was used to probe the process of filament
      formation, i.e., the aggregation-dissociation process. The material with
      nonracemic ligands may form a longer nanoscopic filament.

PMID- 15455444
TI  - Chiral derivatives of 2-(1-naphthyl)-2-phenylacetic acid.
AB  - The spectral properties of diastereomeric esters and amides (1b-20b), derived
      from optically pure 2-(1-naphthyl)-2-phenylacetic acids (1-NPA), were
      systematically investigated. It was found that all compounds prepared exhibit the
      NMR spectral nonequivalence (Deltadelta) with regular sign distribution of
      particular groups according to the predicted model. Further, the analysis of data
      revealed that the phenyl ring is responsible for a shielding effect (upfield
      shift) instead of a naphthyl one. This conclusion is supported by the
      crystallographic analysis showing the almost ap-arrangement of the acid methine
      hydrogen atom and carbonyl group. In this arrangement, the phenyl ring faces
      toward the ester part of the molecule while the naphthyl one is orthogonal to the
      phenyl plane. Therefore, the mutual position of phenyl and alkyl groups with
      respect to the central molecule co-planarity thus determines the chemical shifts
      of the alcohol/amine substituents. The relative magnitude of the Deltadelta
      corresponds to those of Mosher's derivatives.

PMID- 15455445
TI  - Axially dissymmetric N-thioacylated (S)-(-)-1,1'-binaphthyl-2,2'-diamine ligands
      for copper-catalyzed asymmetric Michael addition of diethylzinc to alpha,beta
      unsaturated ketone.
AB  - Axially chiral thioamide ligands L5, L6, L8, L11, and bis(thioamide) ligand L13
      were prepared from the reaction of (S)-(-)-1,1'-binaphthyl-2,2'-diamine with acyl
      chlorides and phosphorus pentasulfide (P2S5). The catalytic asymmetric 1,4
      addition of diethylzinc to alpha,beta-unsaturated ketones was examined using this
      novel chiral ligand system with 28-73% ee in moderate to good yields.

PMID- 15455446
TI  - Etiological and therapeutical observations in a case of belly dancer's
      dyskinesia.
AB  - We report on the case of a woman with belly dancer's syndrome. This case
      presented two peculiarities: (1) the condition was induced by the chronic use of
      clebopride, and (2) abdominal dyskinesias showed a dramatic response to the
      application of transcutaneous electrical nerve stimulation.

PMID- 15455447
TI  - Grip force behavior during object manipulation in neurological disorders: toward
      an objective evaluation of manual performance deficits.
AB  - The control of prehensile finger forces is an essential feature of skilled manual
      performance. The basic aspects of healthy grip force behavior have been well
      documented. In healthy subjects, grip force is precisely adjusted to the
      mechanical object properties. Grip force is always slightly higher than the
      minimum necessary to prevent the object from slipping. When we move a hand-held
      object, grip force is modulated in parallel with movements-induced load
      fluctuations without an obvious delay. The absence of a temporal delay between
      grip and load force profiles suggests that the central nervous system is able to
      predict the load variations before the intended manipulation and consequently
      regulates grip force in anticipation. Feedback from the grasping fingertips is
      used to adjust the level of applied fingertip force efficiently to the actual
      loading requirements. Pathologic grip force control affects the efficiency of
      produced force and the precision of the temporal coupling between grip and load
      force profiles. Here, we review the characteristics of pathologic grip force
      behavior in various neurological disorders. Detailed examination of grip force
      control is simple and well suited for the objective evaluation of impaired motor
      function of the hand and its rehabilitation.

PMID- 15455448
TI  - Sporadic rapid-onset dystonia-parkinsonism syndrome: failure of bilateral
      pallidal stimulation.
AB  - We report on a woman who had a severe sporadic nonprogressive dystonia
      parkinsonism syndrome with rapid onset of symptoms at age 21. Secondary causes
      for dystonia were ruled out. No response to levodopa/carbidopa was seen. The
      patient fulfilled all diagnostic criteria of rapid-onset dystonia-parkinsonism,
      except for autosomal-dominant inheritance. Bilateral deep brain stimulation of
      the globus pallidus failed to alleviate her symptoms.

PMID- 15455449
TI  - Long-term safety, efficacy, dosing, and development of resistance with botulinum
      toxin type B in cervical dystonia.
AB  - Short-term studies of cervical dystonia (CD) have demonstrated botulinum toxin
      type B (Bot B) to be safe and efficacious at doses of 5,000 to 10,000 units, but
      few long-term studies have been published and the safety and efficacy of higher
      doses has not been established. Additionally, there are few studies describing
      the development of resistance to Bot B in those with and without prior resistance
      to botulinum toxin type A (Bot A). We reviewed our experience with 24 patients
      treated with Bot B for up to 64 months. Patients were treated with Bot B for 26.2
      +/- 20.4 months (range, 3-64 months) with a mean treatment dose of 14,828 +/-
      6,824 units (range, 2,500-28,000 units). At last follow-up, 12 patients
      demonstrated ongoing benefit, 8 patients had become secondarily resistant, and 4
      patients were primary nonresponders possibly due to the severity and nature of
      their CD. Nine of the 12 continued responders and 7 of the 8 secondary
      nonresponders to Bot B had prior probable or definite clinical resistance to Bot
      A. No severe adverse events related to Bot B were seen. Treatment of patients
      with severe CD who continue to show a beneficial response to Bot B injections
      commonly requires doses of 15,000 units and rarely greater than 20,000 units.
      Patients may continue to respond for up to 64 months. Prior Bot A resistance may
      be a risk factor for the development of resistance to Bot B; nevertheless, Bot B
      can be a useful long-term alternative in some Bot A-resistant CD patients.

PMID- 15455450
TI  - Finite, spherical coordination networks that self-organize from 36 small
      components.

PMID- 15455451
TI  - Three-dimensional chiral molecule-based ferrimagnet with triple-helical-strand
      structure.

PMID- 15455452
TI  - Unveiling reliable catalysts for the asymmetric nitroaldol (Henry) reaction.

PMID- 15455453
TI  - Atomic-step-templated formation of single wall carbon nanotube patterns.

PMID- 15455458
TI  - New organosilyl derivatives of the Dawson polyoxometalate [alpha2
      P2W17O61(RSi)2O]6-: synthesis and mass spectrometric investigation.
AB  - In the field of functionalized polyoxometalates, organosilyl derivatives of
      polyoxotungstate constitute a special class of hybrid organic-inorganic system.
      The first organosilyl derivative of the monovacant Dawson heteropolyoxotungstate
      [alpha2-P2W17O61]10- was obtained by three different methods. The use of two
      organosilanes as reagents enabled the preparation of the functionalized
      polyoxometalate [alpha2-P2W17O61(RSi)2O]6- in good yield. Electrospray (ESI-MS)
      and matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass
      spectrometry, and 183W, 31P, and 29Si NMR spectroscopy were used to characterize
      the composite systems. In several cases, ESI-MS analyses generated reduction
      processes which were compared to those related to [PMo11VO40]4-, the highly
      reducible Keggin polyoxometalate.

PMID- 15455459
TI  - Continuous arterial spin labeling at the human common carotid artery: the
      influence of transit times.
AB  - In evaluating the sensitivity of arterial spin labeling (CASL) and for
      quantification of perfusion, knowledge of the transit time from the labeling
      plane to the imaging slice is crucial. The purpose of the current study was to
      obtain estimates of transit times relevant under the specific experimental
      conditions of CASL in human subjects using a separate local labeling coil at the
      neck. Specifically, the post-label delay (PLD), i.e. the time between the end of
      the labeling period and the image acquisition, was varied either with or without
      additional application of crusher gradients to suppress intravascular signal
      contributions. The overall sensitivity change for varying the PLD between 1000
      and 1700 ms was low. A tissue transit time from the neck to an axial
      supraventricular section through Broca's knee was obtained by fitting the PLD
      dependence to a two-compartment model. Averaging over subjects yielded 1930 +/-
      110 ms for the tissue transit time, and 73 +/- 5 ml min(-1) 100 g(-1) for the
      cerebral blood flow. Small areas that exhibited a very high signal change upon
      labeling were indicative of regional variation in cerebral blood flow related to
      vascular anatomy.

PMID- 15455460
TI  - Proton T2 relaxation of cerebral metabolites of normal human brain over large TE
      range.
AB  - T2 of NAA, creatine and choline-containing compounds were measured in posterior
      frontal white matter and occipital grey matter in 10 healthy human volunteers.
      Decay curves comprised signals from eight TE times ranging from 30 to 800 ms with
      TR 2000 ms acquired with a PRESS sequence on a 1.5 T clinical scanner.
      Simulations were conducted to assess the precision of T2 estimates from decay
      curves comprising varying numbers and ranges of TE points. Mean and standard
      errors for T2s of NAA, creatine and choline-containing compounds were 300(8),
      169(3) and 239(4) ms in posterior frontal white matter and 256(6), 159(8) and
      249(8) ms in occipital grey matter. In vivo T2s found for choline and NAA were
      shorter than the T2s in the literature. The elevation of literature T2s is
      accounted for by the simulation results, which demonstrated that there is a bias
      towards lengthened T2s when T2 is measured with a maximum TE approximately T2.
      Concentration estimates are at risk of being underestimated if previously
      reported T2 corrections are used.

PMID- 15455461
TI  - Asymmetry analysis of cingulum based on scale-invariant parameterization by
      diffusion tensor imaging.
AB  - Current analysis of diffusion tensor imaging (DTI) is based mostly on a region of
      interest (ROI) in an image dataset, which is specified by users. This method is
      not always reliable, however, because of the uncertainty of manual specification.
      We introduce an improved fiber-based scheme rather than an ROI-based analysis to
      study in DTI datasets of 31 normal subjects the asymmetry of the cingulum, which
      is one of the most prominent white matter fiber tracts of the limbic system. The
      present method can automatically extract the quantitative anisotropy properties
      along the cingulum bundles from tractography. Moreover, statistical analysis was
      carried out after anatomic correspondence specific to the cingulum across
      subjects was established, rather than the traditional whole-brain registration.
      The main merit of our method compared to existing counterparts is that to find
      such anatomic correspondence in cingulum, a scale-invariant parameterization
      method by arc-angle was proposed. It can give a continuous and exact description
      on any segment of cingulum. More interestingly, a significant left-greater-than
      right asymmetry pattern was obtained in most segments of cingulum bundle (-50-25
      degrees), except in the most posterior portion of cingulum (25-50 degrees).

PMID- 15455462
TI  - Revisiting the role of Broca's area in sentence processing: syntactic integration
      versus syntactic working memory.
AB  - Most previous neuroimaging studies of sentence processing have associated Broca's
      area with syntactic processing; however, the exact nature of the processes
      subserved by this brain region is yet not well understood. Although some authors
      suggest that Brodmann area (BA) 44 of the left inferior frontal gyrus (i.e.,
      Broca's area) is relevant for syntactic integration processes, others claim that
      it is associated with working memory mechanisms relevant for language processing.
      To dissociate these two possible functions, the present study investigated
      hemodynamic responses elicited while participants processed German indirect wh
      questions. Activation increases were observed in left BA 44 together with
      superior temporal areas and right hemispheric homologues for sentences with
      noncanonical word order, in which a verb argument was dislocated from its
      canonical position over a relatively long distance. In these sentences, syntactic
      working memory load was assumed to be greatest. In contrast, no activation
      increase was elicited by object-initial as opposed to subject-initial sentences
      that did not differ with respect to working memory costs but with respect to
      syntactic integration costs. These data strongly suggest that Broca's area plays
      a critical role in syntactic working memory during online sentence comprehension.

PMID- 15455464
TI  - Distinguishing between heterogeneity and inefficiency: stochastic frontier
      analysis of the World Health Organization's panel data on national health care
      systems.
AB  - The most commonly used approaches to parametric (stochastic frontier) analysis of
      efficiency in panel data, notably the fixed and random effects models, fail to
      distinguish between cross individual heterogeneity and inefficiency. This
      blending of effects is particularly problematic in the World Health
      Organization's (WHO) panel data set on health care delivery, which is a 191
      country, 5-year panel. The wide variation in cultural and economic
      characteristics of the worldwide sample produces a large amount of unmeasured
      heterogeneity in the data. This study examines several alternative approaches to
      stochastic frontier analysis with panel data, and applies some of them to the WHO
      data. A more general, flexible model and several measured indicators of cross
      country heterogeneity are added to the analysis done by previous researchers.
      Results suggest that there is considerable heterogeneity that has masqueraded as
      inefficiency in other studies using the same data.

PMID- 15455465
TI  - Estimating the demand for health care with panel data: a semiparametric Bayesian
      approach.
AB  - This paper is concerned with the problem of estimating the demand for health care
      with panel data. A random effects model is specified within a semiparametric
      Bayesian approach using a Dirichlet process prior. This results in a very
      flexible distribution for both the random effects and the count variable. In
      particular, the model can be seen as a mixture distribution with a random number
      of components, and is therefore a natural extension of prevailing latent class
      models. A full Bayesian analysis using Markov chain Monte Carlo simulation
      methods is proposed. The methodology is illustrated with an application using
      data from Germany.

PMID- 15455466
TI  - Patient knowledge about drugs prescribed at primary healthcare facilities.
AB  - OBJECTIVE: Providing adequate information to the patients about their drugs is an
      essential principle of rational pharmacotherapy. This study investigates the
      knowledge of general practice patients about their drugs, since the level of
      knowledge of the patient about the medication is highly associated with the
      outcome of the therapy. METHODS: A total of 1618 patients who applied to primary
      healthcare centers in Istanbul and accepted to participate in the study were
      asked about the name(s) and effect(s) of the drug(s) on their prescriptions.
      Factors that might influence the background knowledge and perception of patients
      such as sociodemographic characteristics, drug-use habits and practitioners'
      attitudes were also questioned. Information provided by the patients was compared
      with the prescriptions. RESULTS: Only 10.9% of the respondents could recall the
      names of their drug(s) correctly. Level of education, and gender, had a positive
      impact on recalling drug names. Patients, who received a refill prescription,
      with a chronic disease, and who had self-medication before applying to the health
      center reported more accurate information. Less than half of the practitioners
      had informed their patients about the drug effects; and 7% of the patients have
      been requested to repeat the instructions and warnings about his/her
      medication(s). The patients to name their drugs correctly also knew the drug
      effects twice as much the patients who could not recall their drug(s)' name. The
      drugs which were correctly named were the ones used in chronic diseases.
      CONCLUSION: It appears that patients, particularly who are poorly educated,
      males, and who received a first prescription know little about their prescribed
      drugs. These results suggest that patients' education about drugs is an important
      issue regarding rational drug use which deserves urgent improvement.

PMID- 15455467
TI  - Simultaneous measurement of saturation and relaxation in human brain by
      repetitive magnetization transfer pulses.
AB  - Magnetization transfer (MT) by equidistant pulse trains can be described as being
      analogous to progressive partial saturation, where 'direct' saturation of water
      is amplified by MT contributions that are dependent on macromolecular content and
      differential saturation. This concept was applied to study the transition to
      steady state in the human brain using similar MT-pulses as in imaging. Up to 41
      bell-shaped MT-pulses of 12 ms duration were applied at frequency offsets between
      0.5 and 15 kHz with flip angles between 1080 and 1440 degrees . Central white and
      parietal gray matter was studied in human subjects using STEAM for localized read
      out (TE = 30 ms, TM = 13.7 ms). The apparent degree of saturation, delta(app),
      and the longitudinal relaxation of the water pool during the pulse repetition
      period (PR) were fitted to the transient behavior after signal correction for
      cerebro-spinal fluid. PR was varied between 15 and 100 ms to assess the PR
      dependence of the fitted parameters. The MT-term in delta(app) exceeded the
      direct saturation and attained its maximum at PR > or = 100 ms. The
      macromolecular pool was only partially saturated by a single MT-pulse. The offset
      may be increased to 2.5 kHz to reduce direct saturation without sacrificing MT in
      white matter. The estimated relaxation rates (1.04 +/- 0.11 s(-1) in WM; 0.76 +/-
      0.13 s(-1) in GM) were faster than are commonly observed at 1.5 T. The apparent
      saturation is a measure for MT that is not confounded by relaxation. To maximize
      MT in brain tissue, MT-pulses should be applied at PR = 100 ms or longer. At
      shorter PR, a larger steady state saturation is obtained at the cost of increased
      contributions from direct saturation. Since this accelerates the convergence, PR
      should be decreased to reach the steady state within a specified time. A faster
      transition can always be achieved at a reduced frequency offset via increased
      direct saturation.

PMID- 15455468
TI  - Metabolites from cerebrospinal fluid in aneurysmal subarachnoid haemorrhage
      correlate with vasospasm and clinical outcome: a pattern-recognition 1H NMR
      study.
AB  - Following subarachnoid haemorrhage the most significant complication is sustained
      cerebral vascular contraction (vasospasm), which may result in terminal brain
      damage from cerebral infarction. Despite this, the biochemical cause of vasospasm
      remains poorly understood. In this study, the global high-concentration
      metabolite composition of CSF has been correlated with patient outcome after
      subarachnoid haemorrhage using multivariate statistics and 1H NMR spectroscopy.
      In total, 16 patients with aneurysmal subarachnoid haemorrhage (aSAH) were
      compared with 16 control patients who required a procedure where CSF was obtained
      but did not have aSAH. Multivariate statistics readily distinguished the aSAH
      group from the heterogeneous control group, even when only those controls with
      blood contamination in the CSF were used. Using principal components analysis and
      orthogonal signal correction, vasospasm was correlated to the concentrations of
      lactate, glucose and glutamine. These pattern recognition models of the NMR data
      also predicted Glasgow Coma Score (54% within +/- 1 of the actual score on a
      scale of 1-15 for the whole patient group), Hunt and Hess SAH severity score (88%
      within +/- 1 of the actual score on a scale of 1-5 for the aSAH group) and
      cognitive outcome scores (78% within +/- 3 of the actual score on a 100% scale
      for the whole patient group). Thus, the approach allowed the prediction of
      outcome as well as confirming the presence of aSAH.

PMID- 15455469
TI  - [Progress in the study of Yersinia enterocolitica infections in China].

PMID- 15455470
TI  - [Progress in the study of Q fever in China].

PMID- 15455471
TI  - [Relation between low density lipoprotein receptor gene polymorphism, blood
      lipids, obesity and hypertension].

PMID- 15455472
TI  - [Progress in control and prevention of primary hypertension in the community
      health care center in China].

PMID- 15455473
TI  - [Prevention of plague in China in last 50 years].

PMID- 15455474
TI  - [Epidemiology of sex transmitted diseases and their control strategies in China].

PMID- 15455475
TI  - [Progress in the sero-epidemioloyg].

PMID- 15455476
TI  - Nutrition intervention in the care of persons with human immunodeficiency virus
      infection: position of the American Dietetic Association and Dietitians of
      Canada.

PMID- 15455477
TI  - Schedules of controlled substances: placement of alpha-methyltryptamine and 5
      methoxy-N,N-diisopropyltryptamine into schedule I of the Controlled Substances
      Act. Final rule.
AB  - This final rulemaking is issued by the Deputy Administrator of the Drug
      Enforcement Administration (DEA) to place alpha-methyltryptamine (AMT) and 5
      methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT) into Schedule I of the Controlled
      Substances Act (CSA). This action by the DEA Deputy Administrator is based on a
      scheduling recommendation by the Department of Health and Human Services (DHHS)
      and a DEA review indicating that AMT and 5-MeO-DIPT meet the criteria for
      placement in Schedule I of the CSA. This final rule will continue to impose the
      regulatory controls and criminal sanctions of Schedule I substances on the
      manufacture, distribution, and possession of AMT and 5-MeO-DIPT.

PMID- 15455478
TI  - Double-incision fasciotomy of the leg for decompression in compartment syndromes.
AB  - Surgical decompression remains the only effective treatment for the ischemia of
      the muscles and nerves of the leg that constitutes the principal defects in the
      compartment syndromes. Recently, partial fibulectomy has been proposed as a good
      way to decompress all four compartments instead of the older double incision.
      Both methods are effective in satisfactorily reducing intracompartmental
      pressures, as documented by our wick catheter measurements. However, the double
      incision technique is easier, faster, safer, and is the treatment of choice when
      four-compartment decompressive fasciotomy is indicated.

PMID- 15455479
TI  - [Recombinant activated Factor VII (Novo Seven) for uncontrollable hemorrhage in
      critically ill patients with multiple injuries].

PMID- 15455480
TI  - Multifocal infantile myofibromatosis and generalized fibromuscular dysplasia in a
      child: evidence for a common pathologic process?
AB  - Infantile myofibromatosis (IM) is a condition characterized by the formation of
      spindle cell tumors of skin, soft tissue, and viscera. Although small vessel
      involvement by the process is a frequently identified and indeed diagnostically
      useful histological finding, involvement of large vessels is not widely reported.
      Fibromuscular dysplasia (FMD) is a noninflammatory arteriopathy characterized by
      intimal, medial, and/or adventitial fibroplasias leading to luminal compromise
      and aneurysm formation. Although venous disease has been reported, involvement of
      arterioles and viscera has not been identified. We report a patient in whom IM
      was diagnosed, on the basis of multiple soft tissue tumors present from birth,
      who subsequently developed generalized and ultimately fatal FMD. These two
      conditions exhibit overlapping pathologic features, including pronounced intimal
      fibroplasia. Their occurrence in a single individual may provide insights into
      the pathogenesis of both conditions, suggesting that they represent part of the
      same spectrum of vascular myofibroblastic proliferations.

PMID- 15455481
TI  - MALT Lymphoma in Children: Case Report and Review of the Literature.
AB  - Mucosa-associated lymphoid tissue (MALT) lymphoma predominantly occurs in adults,
      and is rare in children. We report a case of MALT lymphoma involving minor
      salivary gland of the lip in an otherwise healthy 12-year-old boy. This is the
      second case report of MALT lymphoma of minor salivary gland in an immunocompetent
      child. Of 24 cases of MALT lymphomas in children reported in the English
      literature, parotid MALT lymphomas in human immunodeficiency virus (HIV) patients
      and H. pylori infection-associated gastric MALT lymphomas are the most common. As
      in adult cases, most MALT lymphomas in the pediatric age group are localized and
      follow an indolent clinical course, respond well to therapy, and have an
      excellent outcome.

PMID- 15455482
TI  - Melanosis of the areola in dermoscopy.

PMID- 15455483
TI  - Mycophenolate mofetil treatment of a patient with hyperglobulinemic purpura.

PMID- 15455484
TI  - [Primary adenocarcinoma of the urinary bladder: report of one case].

PMID- 15455485
TI  - Profile: Masood Hyder, UN humanitarian coordinator in North Korea.

PMID- 15455486
TI  - Sir Godfrey N. Hounsfield.

PMID- 15455487
TI  - Omalizumab as add-on therapy to inhaled steroids for asthma.
AB  - In the US, subcutaneous administration of omalizumab is indicated for adults and
      adolescents (age greater than or equal to 12 years) with allergic asthma that is
      moderate to severe and inadequately controlled with inhaled corticosteroids. In
      placebo-controlled trials, omalizumab reduces asthma exacerbations and the need
      for inhaled steroids in this group. The value of omalizumab to patients with
      severe asthma (e.g., refractory asthma) has yet to be proven. Data are lacking on
      the efficacy of omalizumab compared to add-on therapies such as inhaled long
      acting beta-2 agonists or anti-leukotriene agents. Further evaluation on
      omalizumab needs to be done in the pediatric population.

PMID- 15455488
TI  - [Izmail Fedorovich Sluchevskii (the 100th anniversary of his birth)].

PMID- 15455489
TI  - Haplotypes, SNPs and disease.

PMID- 15455490
TI  - [Cilia and cystogenesis].

PMID- 15455492
TI  - [Prevalence of mild to moderate chronic kidney disease in the general population
      of Spain. Hortega study].
AB  - BACKGROUND: Although the epidemiology of subjects with end-stage renal disease is
      well-known in Spain, the prevalence of mild to moderate chronic kidney disease
      (CKD) in the general population is unknown. In order to measure this, it is
      necessary to carry out studies in the general population including those who are
      not health service patients. During epidemiology studies, the method of measuring
      glomerular filtration rate can change significantly the measurements of the
      prevalence of mild to moderate CKD. METHODS: Between 1997 and 2000, we performed
      a multi-phase descriptive polistratified epidemiological transversal study. The
      section of public chosen was between the ages of 15 and 85 living in the health
      area of western Valladolid (Spain). We calculated creatinine clearance using four
      methods: serum creatinine concentration, creatinine clearance using 24-hour urine
      samples adjusting the volume to the expected creatinuria with the Walser
      formulas, using the Cockcroft-Gault (CG) equation and applying the Modification
      of Diet in Renal Disease (MDRD) study abbreviated formula. We classified the
      level of kidney function, according to the National Kidney Foundation-Dialysis
      Outcomes Initiative (NFK-DOQI) guidelines. RESULTS: The instances of stages 2 and
      3 CKD rise with age and are more common in women than men. This tendency is
      apparent in middle age and persons of 65 and above. Using the CG method, almost
      half the old women had a stage 3 CKD as opposed to a third of the men. If the
      measurement is performed using the abbreviated MDRD study, there are very few
      differences between the sexes. The prevalence of stage 3 CKD is similar (around
      8%) but the prevalence of stage 2 CKD rises to 60% as opposed to 36% calculated
      using the CG equation. After comparing the results obtained with those of the
      third National Health and Nutrition Examination Survey Study (see table VII), the
      measurements of stage 3 CKD using the CG formula or by means of expected
      creatininuria coincide relatively, although the prevalence of stage 2 CKD is
      higher in persons of 65 and over. If we use the abreviated MDRD study, the
      prevalences increase by more than 20%. CONCLUSIONS: The prevalence of stages 2
      and 3 CKD is clearly influenced by the method of calculation used. The prevalence
      of stage 2 CKD affects at least a third of the general population while those
      affected by stage 3 CKD are between 3.3% and 8.5%.

PMID- 15455493
TI  - [Lercanidipine in diabetic patients with renal failure].
AB  - OBJECTIVE: To evaluate the safe use of a new calcium channel blocker,
      lercanidipine, in diabetic chronic renal failure (CRF) patients. DESIGN AND
      METHODS: The study recruited 42 diabetic CRF patients (creatinine > 1.4 mg/dl for
      males, creatinine > 1.2 mg/dl for females, or creatinine clearance < 70 ml/min).
      Mean age was 68.2 +/- 9.1 years. 53.8% were males and 46.2% females. Three
      patients were type 1 diabetics and 39 ones were type II. All patients were
      receiving ACE inhibitors (67.4%) or angiotensin II antagonist (32.6%) therapy but
      they had higher blood pressure than recommended for CRF patients (130/85 mmHg).
      No patients were under diuretic treatment. Patients were clinically evaluated 1,
      3 and 6 months after starting treatment with lercanidipine. Samples for urine and
      blood examination were taken during the examination. When needed, a third drug
      was added to treatment, excluding diuretics. Creatinine clearance was measured
      using 24 h urine collection. RESULTS: BP significantly decrease from 163 +/-
      18/90 +/- 8 mmHg to 134 +/- 12/77 +/- 9 mmHg. One half of patients showed
      significant reduction of blood pressure, 26.7% reached the target blood pressure
      (< 130/85 mmHg) and 20.0% gets optimal BP control (< 130/85 mmHg). No one patient
      showed untoward effects. No edema was detected nor adverse effects related to
      vasodilatation were found. Plasmatic creatinine did not change (1.9 +/- 0.5
      baseline vs 1.8 +/- 0.5 mg/dl) and creatinine clearance increased at the end
      visit (40.1 +/- 14.5 baseline vs 45.4 +/- 18.2 ml/min) but the difference was not
      significant. Proteinuria was unchanged. CONCLUSIONS: Lercanidipine showed a good
      antihypertensive effect in diabetics CRF patients. It has a good tolerability
      profile and showed neutral effect on plasmatic lipids. Neither impairment of
      renal function nor increment in proteinuria were detected.

PMID- 15455494
TI  - [MIBI and parathyroid gland function in secondary hyperparathyroidism].
AB  - The role of the double phase parathyroid scintigraphy with MIBI in the primary
      hyperparathyroidism has been well studied. The present work analyzes the benefit
      of this image technique in the diagnosis and therapeutic approach to uremia
      associated hyperparathyroidism. We studied 18 dialysis patients with clinical and
      analytical data of hyperparathyroidism. All of them were receiving treatment with
      i.v. vitamin D. We carried out two scintigraphic studies, the first under basal
      conditions (without changes in treatment) and the second one, a week later after
      the stimulation of the parathyroid gland through the cessation of the treatment
      with vitamin D and phosphorus binders, and the use of a low-calcium dialysate. In
      the basal study, fourteen patients had a positive uptake test in at least one of
      the four glands. These patients had significantly higher PTHi levels than those
      with a negative scintigraphic study. After the stimulation test, we found a
      statistically significative rise in PHTi (644 vs 979 p < 0.001) and phosphorus
      levels (5.8 vs 7.3; p < 0.01), a slight fall in calcium levels (p = NS) and a
      statistically significative increment in the score of scintigraphic captation
      (5.5 +/- 4.5 vs 6.8 +/- 5; p < 0.05). We found a statistically significative
      correlation between the PTHi level and the score of scintigraphic uptake, in the
      basal study (r = 0.6, p < 0.01) and after stimulation (r = 0.6, p < 0.01). The
      only variable associated with the scintigraphic uptake was PTHi, justifying 31.1%
      of the variance in the first study and 32.7% in the second. In conclusion, the
      MIBI scintigraphic is a useful exploration in the uremic patient with
      hyperparathyroidism, as it predicts the functional state of the parathyroid
      glands according to uptake intensity. The stimulation test could be useful in
      planning therapy, but some of its characteristics need to be established, such as
      the precise time to reach the maximum level of parathyroid stimulation.

PMID- 15455495
TI  - [Reticulocyte response after immediate withdrawal of recombinant human
      erythropoietin in chronic hemodialysis patients].
AB  - The sudden interruption of recombinant human erythropoietin (rHuEPO) in end-stage
      renal disease (ESRD) patients leads to rapid anemization. The mechanisms of this
      phenomenon are, however, insufficiently understood. The present study examined
      the response to immediate rHuEPO withdrawal in dialysis patients. METHODS: 10
      chronic hemodialysis (HD) patients regularly receiving rHuEPO were studied.
      rHuEPO was stopped and reinitiated after 7 days. Reticulocyte profile,
      haemoglobin and haematocrit were measured at 0, 7 and 15 days. As a complementary
      study, and with the purpose of analyzying whether uremia was a relevant factor,
      10 non-uremic male Wistar rats were treated with rHuEPO. After two weeks, rHuEPO
      was withdrawn in 5 animals, and continued for 7 additional days in the remainder.
      The same variables than in the human study were determined. RESULTS: Changes in
      reticulocyte subtypes from baseline to day 7 were: total 18.2 +/- 0.9 vs 14.3 +/-
      1.8% (p < 0.06); high-fluorescence (HFR): 2.6 +/- 0.4 vs 0.75 +/- 0.2 (p <
      0.001); medium-fluorescence (MFR): 13.0 +/- 1.1 vs 6.6 +/- 0.9% (p < 0.02); and
      low-fluorescence (LFR): 84.2 +/- 1.4 vs 92.7 +/- 1% (p NS). The baseline pattern
      was recovered upon 7 days of rHuEPO reinitiation (p NS). Mean hemoglobin and
      hematocrit decreased by day 14 (p < 0.02) in spite of rHuEPO reinitiation at day
      7. In non-uremic rats, changes were similar to that in the ESRD patients.
      CONCLUSION: rHuEPO induces changes in the reticulocyte pattern, consisting in a
      reduction of immature reticulocytes. These changes appear to be independent of
      the presence of uremia. Accordingly, complete rHuEPO withdrawal in HD patients
      will cause a rapidly-developing anaemia due to an alteration in the reticulocyte
      maturation series; therefore, sudden rHuEPO interruption should be avoided
      whenever is possible. As a collateral application, the specific changes described
      herein have potential use for detecting illegal administration of rHuEPO.

PMID- 15455496
TI  - [Utility of intra-access pressure].
AB  - Monitoring of vascular access is essential for clinical evaluation on
      hemodialysis patients, detects early disfunction of access, allows adequate
      dialysis and decreases the morbidity associated. Although is demonstrated that
      intra-access pressure (IAP) is a good method of screening to evaluate arterial
      venous (AV) fistulas, its utility is uncommon because its measurement requires a
      complex system. We would like to validate the utility of IAP monitoring using a
      simplified measure of IAP and its relation with other methods of screening in
      detecting stenoses prior to thromboses of AV grafts. We studied 24 AV grafts of
      24 patients during 18 months we measured arterial pressure, mean arterial
      pressure (MAP), dynamic venous pressure, IAP, Kt/v, URR, recirculation index
      (RI), access flow and color Doppler flow, dividing the patients in two groups,
      with stenoses or not, if IAP/MAP > 0.5 and stenoses > 0.50 by Doppler we
      performed arteriography and percutaneous transluminal angioplasty with stent if
      stenoses exits. The values of IAP, MAP, RI were higher significantly in the
      stenoses group with increase of vascular access in grafts were dilation by
      angioplasty was made. All stenoses detected with IAP were confirmed by Doppler
      and arteriography but one. We conclude that IAP is an early, useful, easy,
      effective method in detecting stenoses of AV grafts prior to thrombosis.

PMID- 15455497
TI  - [Self esteem pre and post renal transplantation in Mexican adolescents].

PMID- 15455498
TI  - [Association between membranous glomerulonephritis and Crohn's disease].
AB  - We report the case of a 37 year old man who suffered from Crohn's Disease (CD),
      and was receiving treatment with mesalazine (5-ASA). Nine years after the
      diagnosis, because of detecting a slight proteinuria, a renal biopsy is made,
      being the anatomo-pathologic result compatible with membranous glomerulonephritis
      (MGN). Checking previous literature we have only found two cases reported of MGN
      in coincidence with Inflammatory Bowel Disease (IBD), one in association with
      Ulcerative Colitis and the other with Crohn's Disease in a 12 years old boy. This
      is, therefore, the second case presenting MGN associated with CD and the first in
      an adult patient.

PMID- 15455499
TI  - [Arteriovenous fistula: complication of renal biopsy. Superselective
      embolization].
AB  - The arteriovenous fistula can be a major and late complication of percutaneous
      renal biopsies of native kidneys. The incidence of arteriovenous fistulas appears
      to be low and has been infrequently mentioned in large series of biopsies
      although there are a number of individual reports. In most part of cases, no
      systemic effects of the arteriovenous fistulas were observed, so they close by
      themselves. Optimization of renal biopsy techniques aims not only at obtaining
      kidney tissue technically adequate for diagnosis, but at reducing biopsy-induced
      complications. When these complications are done, the new transvascular
      techniques can get the healing of fistula with the embolism by catheters. We
      describe the case of a 37-year-old woman who had chronic renal failure by a
      possible chronic glomerulonephritis. She developed deterioration of renal
      function after the percutaneous renal biopsy. An arteriovenous fistula of high
      flow was detected by Doppler ultrasound. Then, it was confirmed angiographically
      and closed by embolism's catheter without damage of renal tissue.

PMID- 15455500
TI  - [Membranous nephropathy associated to autoimmune thyroiditis, chronic
      pancreatitis and suprarrenal insufficiency].
AB  - A 33 year old female was admitted to the hospital to study aedema and bocio, A
      nephrotic syndrome was diagnosed and the renal biopsy demonstrated membranous
      glomerulonephritis, stage II. She was also diagnosed of Hashimoto's autoinmmune
      thyroiditis: TSH (41.5 uUl/ml), T4 (0.07 ng/dl), antithyroglobuline (1/2560) and
      antimicrosome (1/6400). Four year latter she was diagnosed of autoinmmune
      pancreatitis, without evidence of diabetes mellitus or exocrine pancreatic
      insufficiency. Eight years latter she was diagnosed of primary autoimmune
      suprarrenal insufficiency: basal cortisol: 2.7 mcg/dl, post ACTH estimulated
      cortisol: 5.6 mcg/dl, antinuclear antibody (1/160) and antiparietal (1/320). We
      present a pluriglandular autoimmune syndrome with membranous glomerulonephritis,
      thyroiditis, pancreatitis and suprarrenal insufficiency. To the best of our
      knowledge this complex syndrome has not been previously described.

PMID- 15455501
TI  - [Angioradiology as diagnosis and treatment of a pseudoaneurysm in an internal
      arteriovenous fistula].

PMID- 15455502
TI  - [Rhabdomyolysis secondary to the interaction of statins with macrolides in a
      renal transplant patient].

PMID- 15455503
TI  - [Massive hemothorax 48 hours after internal jugular vein catheterization without
      echographic guidance].

PMID- 15455504
TI  - [Concordance between the ultrasonic dilution technique and echocardiography for
      measuring cardiac output in hemodialysis patients].

PMID- 15455505
TI  - [NOS3 polymorphism and reflux nephropathy].

PMID- 15455506
TI  - [Toxic shock syndrome in 3 children].
AB  - A 16-year-old and a 10-year-old girl were admitted with general signs of illness,
      and respectively a green vaginal discharge and a panaritium. They recovered
      following antibiotic treatment and surgical relief of the panaritium. A 2-year
      old boy became ill the morning after eating tainted cold meat; he died in the
      course of the following night. In all 3 patients Staphylococcus aureus was
      incubated with the toxic-shock-toxin-1-gene and/or the enterotoxin-A-gene. These
      3 cases occurred within one year in a general hospital. TSS probably occurs more
      frequently than is generally assumed. Given that it is a life-threatening
      disease, rapid diagnosis is of major importance.

PMID- 15455507
TI  - [Report from the Health Council of the Netherlands on disputed memories].
AB  - The Health Council of the Netherlands recently has published an advisory report
      to the Minister of Health, Welfare and Sport on 'Disputed Memories'. The
      committee, which was established to formulate the report, has answered questions
      about the accessibility of memories of traumatic events, about the circumstances
      that might make memories accessible again, and about the possibility of recalling
      memories of events that were never experienced. The role of psychotherapy in
      retrieving traumatic memories is discussed extensively, leading to specific
      recommendations. In contacts with patients and law enforcement agency therapists
      are expected to refrain from judgments about the historical truth of recovered
      memories.

PMID- 15455508
TI  - [Fifty years of treating stuttering in young children].
AB  - Developmental stuttering involves a disruption in the smooth connection of sounds
      or syllables that is characterised by multiple interruptions within a word, such
      as repetitions of sounds, syllables and parts of words, elongation of words and
      blockades. During the course of the past fifty years, three phases can be
      distinguished in the management of developmental stuttering, characterised by a
      shift in stress from the environmental factors to the role of the organic, i.e.
      non-psychological, factors. Initially, the parents of toddlers and pre-school
      children were advised to pay no attention to stuttering behaviour. Then the
      problem would disappear the quickest of its own accord. After 1985, the stress
      came to be placed on reducing the level of expectations, for example by speaking
      to the child more slowly and using shorter and less complex sentences. Another
      new aspect was that the parents learned to discuss stuttering with the child in a
      sympathetic and accepting manner. Since 2000, an approach has been introduced in
      the Netherlands in which parents are taught to respond verbally to both fluent
      and non-fluent speech. Emphasis is given to rewarding fluent speech, such as in
      the Australian Lidcombe Program, but the parents are also taught to react to
      stuttered speech once in a while. At present, early treatment is accepted as a
      way of preventing chronic stuttering, even if this means that some children will
      be treated that would have recovered in any case and even though the exact yield
      is not yet clear. Clinical practice shows that early treatment almost always
      succeeds in limiting the severity of stuttering to a mild form.

PMID- 15455509
TI  - [Nutrition and health--carbohydrates, the risks to health from the postprandial
      glycaemic response and the possibilities for its manipulation].
AB  - Carbohydrates are the most important source of food-derived energy. The metabolic
      effects of different types of carbohydrate can vary considerably, partially due
      to differences in glucose and insulin response. Several studies indicate that
      postprandial hyperglycaemia is associated with an increased risk of
      cardiovascular disease in patients with diabetes mellitus. For these patients,
      and possibly also for individuals with impaired glucose tolerance as well as for
      the healthy population at large, it may be of benefit to prevent postprandial
      hyperglycaemia. In order to manipulate the postprandial glycaemic response, an
      understanding of the underlying mechanisms of this response is crucial. The
      postprandial blood glucose level is influenced by a number of factors, such as
      the amount and type of ingested carbohydrates, gastric emptying rate and
      digestion and secretion of gastrointestinal and other hormones. Different
      approaches can be chosen to prevent postprandial hyperglycaemia, including
      changes in the diet and the use of drugs that delay gastric emptying or digestion
      of carbohydrates. The administration of gastrointestinal hormones or manipulation
      of the secretion of these hormones, are also possibilities. Investigating the
      regulation of the postprandial blood-glucose concentration and its possible
      manipulation could result in new approaches to preventing postprandial
      hyperglycaemia.

PMID- 15455510
TI  - [Diagnostic image (202). A newborn with subfebrile temperature and skin lesions.
      Staphylococcal scalded skin syndrome].
AB  - A 6-day-old boy suffered from subfebrile temperature and progressive skin lesions
      with epidermolysis, due to Staphylococcus aureus: staphylococcal scalded skin
      syndrome.

PMID- 15455511
TI  - [Increased consultations and numbers of sexually transmitted diseases at the STD
      clinic of Utrecht, 1994-2002].
AB  - OBJECTIVE: To determine trends in numbers of visitors and their demographic
      characteristics, reasons for visit, number of STDs and high-risk groups. DESIGN:
      Secondary analysis of registration data. METHOD: Data of every client that
      visited the STD clinic in Utrecht, the Netherlands, were aggregated from 1994 to
      2002 in order to analyse trends. RESULTS: The number of visitors as well as the
      number of STDs rose strongly over the period investigated. The age of the
      visitors decreased. In 1994 17% of the visitors was born outside the Netherlands,
      in 2002 6%. The majority of the clients (56%) visited the STD clinic to get
      themselves tested preventively and 27% came because of symptoms. Visitors with
      symptoms or who were warned by others had a three-fold increased risk of having
      an STD. Other risk groups were: homosexual men, visitors born outside the
      Netherlands and visitors who have had an STD before. Groups with an increased
      risk of having a Chlamydia trachomatis infection were: visitors aged under 34
      years old and visitors born in Morocco, Surinam and the Antilles. The number of
      Chlamydia infections rose sharply among homosexual male visitors. CONCLUSION: The
      increase in the number of visitors and of STD requires an increase in STD
      prevention, aimed at high-risk groups. More research is needed into the limited
      help-seeking behaviour of immigrants and more attention needs to be paid to
      Chlamydia trachomatis infections among homosexual men.

PMID- 15455512
TI  - [Subcutaneous nodules with malignant presentation, but caused by infection].
AB  - Three patients, a woman aged 32, a boy aged 6.5 and a man aged 56 years,
      presented with a subcutaneous mass suggesting a malignancy: respectively a
      rubbery swelling, painful to the touch below the left scapula, a partly massive,
      partly soft swelling on the inside of the left upper leg, and a non-fluctuating
      mass near the right eighth rib, parasternally. Additional diagnostic
      investigation revealed an infectious cause: respectively Mycobacterium
      tuberculosis, Bartonella henselae and Salmonella typhi. Antimicrobial therapy was
      successful. Subcutaneous masses suspected of being a benign or malignant tumour
      are sometimes caused by an infection. The differential diagnosis is extensive.
      Sometimes the travel anamnesis yields helpful information. It is concluded that
      besides histopathological examination, microbiological investigation can play a
      major role in the evaluation of subcutaneous masses.

PMID- 15455513
TI  - [Accelerated elimination using hemoperfusion in a patient with phenobarbital
      intoxication].
AB  - A 44-year-old female was found comatose after attempting suicide. Toxicological
      screening showed phenobarbital intoxication. The patient was treated
      symptomatically. After ten days her serum level of phenobarbital still had not
      decreased and she was not clinically recovered. The patient was transferred to
      another hospital for hemoperfusion to decrease the level of phenobarbital. After
      hemoperfusion the level of phenobarbital dropped significantly and the patient
      recovered neurologically. Phenobarbital has a long elimination half-life and for
      this reason it is advisable to use means to accelerate clearance until the
      clinical condition of the patient shows improvement. Multiple-dose activated
      charcoal effects the elimination of phenobarbital. If elimination needs to be
      speeded up, then hemoperfusion can be considered. If this technique is
      unavailable, hemodialysis is a good alternative.

PMID- 15455514
TI  - [National registry and DNA-bank of patients with congenital heart disease: the
      CONCOR-project].
AB  - Although survival of patients with congenital heart disease has dramatically
      improved since surgical repair has become available, cure is seldom achieved.
      Exact data on long-term outcome are not available, however, because a national
      registry is lacking. Furthermore, little is known about the role of genetic
      defects in the development of congenital heart disease. The CONCOR-project
      (CONgenital CORvitia) has been set up to facilitate the investigation of the long
      term outcome and molecular basis of specific congenital heart defects and their
      treatment. It will also facilitate the development of an efficient organisational
      structure for the improvement of healthcare for patients with congenital heart
      disease.

PMID- 15455515
TI  - [Value of cost-utility analysis].

PMID- 15455516
TI  - [Health care usage by Moroccans and Turks compared to the indigenous Dutch
      population: no higher consumption of health care and lower medication cost].

PMID- 15455517
TI  - [Pregnancy termination in the second trimester with vaginally administered
      dinoprostone followed by intravenous sulprostone, for the indication 'foetal
      congenital defects'; results of a retrospective study].

PMID- 15455518
TI  - [Diagnostic image (188). A man suffering from a swollen and red arm].

PMID- 15455519
TI  - ['The rumbling of shaking brains'; the treatment of traumatic skull and brain
      injury in the Netherlands in the 17th century: 7 case reports from Observationes
      medicae by Nicolaes Tulp].

PMID- 15455520
TI  - [Population health in some of the Northern regions].
AB  - The conditions and dynamic changes of the most important indices related with
      population health in a number of Northern regions of the Russian Federation are
      under discussion. A conclusion is made that they are predetermined by migration
      processes, latitude effects and peculiarities of production activity.

PMID- 15455521
TI  - [Some peculiarities of the life mode in groups of persons with different-value
      orientations].

PMID- 15455522
TI  - [The vital potential of population during the market-reform period].
AB  - Estimates of the vital potential of population in the Astrakhan Region during the
      1990-2000 market reforms, which were obtained on the basis of the continuous
      statistic observations of the total number of births and deaths during the
      mentioned period as well as on the basis of demography tables and potential
      demography, are described in the paper. An evaluation of man's "weight",
      expressed in man-years, is defined with respect to age and sex. The below
      phenomena are typical of the reform time: prevalence of the share of female vital
      potential; functionality of the life potential of citizens aged 0 to 19 and 20 to
      59; a decreased role of the life potential of citizens aged 0 to 19 due to a low
      fertility; a diminished share of the life potential among able-bodied men; a
      decreased correlation index of the life potential of men versus women; a growing
      life potential in children aged above 1 year due to the paradox of the mean life
      expectancy; an increasing life potential within the age range of 10 years due to
      a dropped birth rate in the 90-ies and to the aging process because of the low
      birth rate and, correspondingly, low children's mortality rate; and compensation
      of losses in the life potential of men and women primarily due to the aging
      process.

PMID- 15455523
TI  - [A medical-and-social description of student youth in the Republic of Komi].
AB  - Ensuring a better health among youth in the North of Russia is an element of the
      unified training system of any personnel because young northerners are not only a
      basis for working activities in the northern latitudes after they graduate from
      educational facilities, they are also an important component of the country's
      intellectual potential. Definition of reasons having a positive or negative
      effect on the health of student youth under the conditions of a northern city is
      possible only if the social, domestic, natural-climatic and ecological
      characteristics of the environment are thoroughly investigated. The health
      condition of student youth is described with respect to the physical development
      parameters, morbidity with or without working (educational) disablement and to
      sociological questioning results.

PMID- 15455524
TI  - [Specificity of the physical training of children with minimal brain dysfunction
      carried out with respect to a condition of the locomotor system].

PMID- 15455525
TI  - [Specific features of the lethality rate among population in the Far East Federal
      Okrug].

PMID- 15455526
TI  - [The information degree of students at medical higher institutions on the rights
      of patients].

PMID- 15455527
TI  - [A structure of the service on prevention of occupational pathologies in a large
      industrial city].
AB  - The reform of the medical service dealing with occupational pathologies in the
      city of Kazan, introduction of new management conditions involving the market
      economy tools and emergence, in this connection, of patient-care and prevention
      facilities of different organizational-and-legal types had a negative effect on
      the health of employees occupied at hazardous and dangerous enterprises. Data
      related with the system of periodical prevention measures undertaken for the sake
      of health protection of able-bodied population are elucidated; methods of
      promoting the structure and management of the occupational-pathology service
      functioning under the conditions of a big industrial city are suggested.

PMID- 15455528
TI  - [Training of experts in family medicine].
AB  - Issues related with training of pre-graduate and postgraduate general physicians
      (family doctors) and of nurses with higher education in the field of family
      medicine at the chair of polyclinic therapy are under discussion in the paper.
      The authors believe that the quality of training of experts in the field of
      family medicine is to a great extent predetermined by the efficiency of rendering
      the primary medical-and-social care to population.

PMID- 15455529
TI  - [The medical-and-genetic training of family physician].
AB  - The development of family medicine and promotion of genetic approaches to
      maintaining the health of population are under discussion in the paper. The
      necessity of training a new generation of physicians by using special programs is
      substantiated. The system approach to the training of family doctors must
      comprise, apart from clinical disciplines, the knowledge of human genetics as of
      a leading medical-and-biological branch of science. The significance of family
      related research and analysis of pedigree (for the sake of accurate diagnosis and
      prevention of diseases) are demonstrated.

PMID- 15455530
TI  - [Main trends of marketing promotion of medical services at commercial
      institutions].

PMID- 15455531
TI  - [Promotion of the occupational-disease prevention among industry workers in a
      large industrial city located in the Republic of Tatarstan].

PMID- 15455532
TI  - [Psychological diagnostics as a method of defining the medical-and-social needs
      of teenagers].

PMID- 15455533
TI  - [The quality of small-age children monitoring in city clinics].
AB  - A special study was undertaken in three pediatric clinics of Makhachkala
      (Republic of Dagestan) for the purpose of elaborating methodological
      recommendations targeted at promoting the quality and efficiency of children
      monitoring. The quality of patient-care was studied on the basis of expert
      evaluation of 565 outpatient's cards of small-age children. The expert evaluation
      showed that the monitoring of the above category of children is up to the mark.
      Inferior nursing by physician was registered in 5.4% of cases; paramedical
      personnel failed to nurse babies of the 1st life year in 8.8% of cases. The
      regularity of children's monitoring in clinics was adhered to in above one half
      of cases; babies of the 1st life year were transferred on artificial feeding
      without strong reason in 52.9% of cases; and the time of adding additional
      feeding was not observed in 25% of cases. Methodological recommendations aimed at
      promoting the quality and efficiency of small-children monitoring in city clinics
      were elaborated on the basis of the study results.

PMID- 15455534
TI  - [Perfection of the material motivation system for medical employees].

PMID- 15455535
TI  - [Significance of modernization of the social rehabilitation system within
      promotion of the nursing care].
AB  - A specially elaborated system-module approach, that contributes to shaping, in
      medical students, the moral principles for their occupational activity, is
      suggested. A continuous humanistic-training system embracing the educational and
      pedagogic processes is elaborated; the system is a principally new type of
      orientation of medical personnel aimed at the medical-and-psychological
      adaptation and rehabilitation of elderly population.

PMID- 15455536
TI  - [Structure of surgical treatment of osteochondrosis compression complications in
      the settings of a specialized surgery center with the round-the-clock short-stay
      hospital].

PMID- 15455537
TI  - [Experience of functioning of the psychological- medical- and pedagogical
      commission at psychiatric hospital].
AB  - Psychological- medical- and pedagogical commissions (PMPC) are most often
      established at educational institutions. However, children cannot be thoroughly
      examined in educational settings in certain cases; therefore, the physicians fail
      to diagnose mental deficiency in children due to insufficiently careful
      examinations. Correspondingly, PMDCs, when established at patient-care and
      preventive facilities, ensure a more accurate diagnosis and determination of an
      intellectual-deficiency degree in children or teenager; they also provide for
      elaborating a set of psychological- medical- and pedagogical measures. The
      experience of establishing PMPC at a regional patient-care and preventive
      facility, as well as of its cooperation with educational institutions and with
      social assistance organizations and its functional peculiarities within the
      structure of the patient-care facility are analyzed in the paper. Recommendations
      are defined on cooperation between psychiatrists, psychologists, social
      activists, pedagogues and of other experts working for such commissions.

PMID- 15455538
TI  - [Socially significant morbidity of population in the Republic of Tajikistan].

PMID- 15455539
TI  - [Medical aspects related with the activities of the Charity Society for the poor
      and sick children].

PMID- 15455540
TI  - Proton magnetic resonance spectroscopic imaging of cerebral gliomas: correlation
      of metabolite ratios with histopathologic grading.
AB  - BACKGROUND: Magnetic resonance spectroscopic imaging (MRSI) can provide spatially
      encoded metabolite information and improve tissue specificity in human brains.
      The major goal of this study was to evaluate the correlation of metabolite ratios
      measured by MRSI with histopathological grading of cerebral gliomas. METHODS:
      Twenty-seven patients with cerebral gliomas were referred consecutively for pre
      surgical evaluation. The lesions included 10 grade II, 5 grade III, and 12 grade
      IV gliomas. MRSI data were acquired during the same session of conventional
      magnetic resonance imaging and analyzed in terms of N-acetylaspartate (NAA),
      creatine-phosphocreatine (Cr), choline-containing compounds (Cho), and lactate.
      RESULTS: There were significantly lower NAA/Cr and higher Cho/Cr, Cho/NAA and
      (Cho+Cr)/NAA ratios (ps < 0.001) in gliomas than in normal tissues. There were
      significantly lower NAA/Cr and higher Cho/NAA and (Cho+Cr)/NAA ratios (ps < or =
      0.05) in World Health Organization (WHO) grade III or IV gliomas than in grade II
      gliomas. A significant correlation was identified between the (Cho+Cr)/NAA ratio
      and WHO grade (p < 0.05). There was no significant metabolite difference between
      grade III and grade IV tumors (ps > 0.1), or significant difference in lactate
      occurrence rates among different grades (p = 0.26). CONCLUSIONS: Proton MRSI can
      provide in vivo information about the metabolic status of cerebral gliomas, and
      the (Cho+Cr)/NAA ratio can discriminate different grades better than other
      metabolite ratios. However, substantial overlap of metabolite ratios among
      different severities of malignancy makes it impossible to confirm the WHO grade
      of a specific cerebral glioma by using clinical MRSI.

PMID- 15455541
TI  - Comparison of multiplex polymerase chain reaction, culture, and serology for the
      diagnosis of Bordetella pertussis infection.
AB  - BACKGROUND: Accurate diagnosis of Bordetella pertussis infection is difficult.
      Polymerase chain reaction (PCR) tests are more sensitive than culture, but the
      reported sensitivity is variable. We prospectively compared the performance of
      culture, serology, and a multiplex PCR for the detection of B. pertussis.
      METHODS: A total of 193 paired nasopharyngeal (NP) swab specimens were examined
      by both culture and a multiplex PCR. Serology results were available in 103
      patients. Medical charts of the patients with discrepant laboratory findings were
      reviewed and compared with the United States Centers for Disease Control and
      Prevention (CDC) clinical case definition. RESULTS: Of the 193 specimens, 11 were
      positive on both culture and PCR, and 14 were positive on PCR only. Of the 103
      specimens with serology results, 3 were positive with all three methods, and 69
      were negative with all methods. Eleven of the 14 PCR-positive only cases and 6 of
      the 19 serology-positive only cases were defined as true pertussis cases
      according to an expanded standard which includes either (1) culture positive or
      (2) PCR or serology positive with clinical features fulfilling the CDC clinical
      case definition and the patients having received macrolides treatment for more
      than 10 days. The sensitivity and specificity of the multiplex PCR were 79% and
      98%, respectively, while those for serology were 47% and 85%, and for culture 39%
      and 100%. CONCLUSIONS: Our data confirm the superior sensitivity of the multiplex
      PCR in detection of B. pertussis, compared with conventional culture and
      serology. Clinical validation indicates that the multiplex PCR offers specific
      detection of B. pertussis from NP specimens.

PMID- 15455542
TI  - Do consumers in Taiwan need physician information?
AB  - BACKGROUND: This article was written to determine the extent of consumers' needs
      for physician information and what information consumers use in decision making
      when selecting a physician. METHODS: To collect data, a self-administered
      questionnaire was hand-delivered to 700 patients who visited the general surgery
      outpatient departments of seven hospitals during June 2003. A multiple logistic
      regression was conducted to identify the statistically significant factors
      related to patients' needs to use physician information. RESULTS: Of the
      respondents (N = 687), 74.7% felt they "greatly needed" or "needed" physician
      information. About 90% of respondents would "certainly" or "possibly" change
      physicians if the performances of their physicians shown by physician profiling
      were not as good as others. Respondents ranked the three most needed physician
      information as specialties, malpractice history, and overall patient satisfaction
      level. The multiple logistic regression showed that respondent's age, hospital
      level, personal monthly income, and whether they had compared medical care
      quality provided by neighborhood physicians had significant relationships with
      the respondent's needs for physician information after adjusting for other
      factors. CONCLUSIONS: This study found that 88.1% of respondents were in need of
      some amount of physician information. This is in light of calls for physician
      profiling from consumer-oriented organizations to assist consumers in selecting
      suitable physicians. It is recommended that the healthcare industry in Taiwan
      make a significant investment in a physician profiling system. The performance
      measures of this physician profiling system should be developed based on inputs
      from consumers, physicians, insurance companies, and researchers in this field.

PMID- 15455543
TI  - Visual results and complications after trans pars plana vitrectomy and lensectomy
      for lens dislocation.
AB  - BACKGROUND: The aim of this study is to determine the relationship between the
      cause of lens dislocation and visual outcomes with complications in patients
      undergoing trans pars plana vitrectomy (TPPV) and trans pars plana lensectomy
      (TPPL) for lens dislocation. METHODS: This retrospective study was carried out
      from July 1995 through November 2003. After excluding patients with previous
      retinal detachment or combing lens dislocation and post-TPPV/TPPL follow-up
      intervals of less than 6 months, 36 eyes from 36 patients who had undergone
      vitrectomy and lensectomy for lens subluxation or dislocation due to trauma or
      intraocular surgery were examined. Their presenting features and complications
      were recorded. The relationship between the cause of lens dislocation and visual
      outcome with complications was tested using Fisher's exact test. RESULTS: The
      cause of lens dislocation included blunt and penetrating eye trauma, and
      intraocular surgery. Final best-corrected visual acuity was 20/40 or better in
      45% of eyes in the traumatic arm and in 31% of eyes in the iatrogenic arm. Visual
      acuity improved after TPPV/TPPL in 90% of the eyes in the traumatic arm and in
      81% of the eyes in the iatrogenic arm. Of all of the eyes, 39% had significant
      complications affecting postoperative visual outcomes, including retinal
      detachment, cystoid macular edema, vitreous hemorrhage and glaucoma. CONCLUSIONS:
      There were no significant differences in visual outcomes and complications
      between the traumatic and iatrogenic arms of the study. Therefore, the cause of
      lens dislocation was not a predictor of visual outcomes. Nonetheless, posterior
      segment complications including retinal detachment and glaucoma were major causes
      of poor postoperative visual outcomes.

PMID- 15455544
TI  - Vesicoureteral reflux in hospitalized children with urinary tract infection: the
      clinical value of pelvic ectasia on renal ultrasound, inflammatory responses and
      demographic data.
AB  - BACKGROUND: The aims of this study were to determine whether renal pelvis
      dilation on ultrasound was reliable in predicting vesicoureteral reflux (VUR) and
      to assess the relationship of other clinical information of VUR in children with
      urinary tract infection (UTI). METHODS: We retrospectively reviewed clinical
      data, renal echo, and voiding cystourethrogram (VCUG) results in hospitalized
      children with their first episode of UTI, aged from 1 month to 5 years, during a
      1-year period. RESULTS: There were 114 children with 228 kidneys eligible for the
      study. Unilateral pelvis size greater than 8 mm had 2.4 (p = 0.049, 95% CI: 1.0
      5.9) and 3.7 (p = 0.025, 95% CI: 1.2-11.3) times greater risk for VUR and severe
      reflux, respectively. The sensitivity in detecting severe reflux was 27.8%, and
      the specificity was 90.5%. The positive and negative predictive values in
      suggesting severe VUR were 20.0% and 93.6%, respectively. The sum of bilateral
      pelvis sizes greater than 16 mm had higher risk for VUR and severe reflux (4.1
      and 4.6 times) and similar specificity and negative predictive value for severe
      reflux. Age, gender, C-reactive protein, leukocytosis, pyuria and acute
      pyelonephritis did not show significant relationships to the reflux. CONCLUSIONS:
      Unilateral pelvis size greater than 8 mm or the sum of the bilateral pelvis sizes
      greater than 16 mm was associated with VUR, especially severe VUR. The
      possibility of severe reflux was lower than 10% when the reverse criteria were
      applied. However, the dilation of the renal pelvis did not predict all VUR
      precisely. We concluded that VCUG should still be performed in hospitalized
      children with UTI.

PMID- 15455545
TI  - The relationship between the flexible flatfoot and plantar fasciitis:
      ultrasonographic evaluation.
AB  - BACKGROUND: The purpose of this study was to investigate the relationship between
      flexible flatfoot and plantar fasciitis. METHODS: Twenty-three subjects with
      flexible flatfoot and 23 subjects with normal arched feet were enrolled.
      Footprint analysis was used to evaluate the foot conditions in both groups to
      calculate the individual arch index. We compared the sonographic images of
      plantar fascia in the flexible flatfoot group with the normal arch group using
      high-frequency ultrasound. RESULTS: The analysis results indicated that the
      thickening of the plantar fascia in the flexible flatfoot group was significantly
      different from the normal arch group. In the flexible flatfoot group, 10 of 23
      patients (43.4%) had plantar fasciitis, but only two subjects (8.7%) in the
      normal arch group had plantar fasciitis. CONCLUSIONS: There was a higher
      incidence of plantar fasciitis in the flexible flatfoot group than the normal
      arch control group in this study.

PMID- 15455546
TI  - Anesthetic management of a patient with Alagille's syndrome undergoing living
      donor liver transplantation without blood transfusion.
AB  - Alagille's syndrome (AGS), which has five main characteristics including chronic
      cholestasis; typical peculiar facies; posterior embryotoxon; butterfly-like
      vertebral-arch defects; and cardiovascular malformations, is rarely seen in
      Taiwan, especially in a liver transplantation setting. We present the successful
      anesthetic management of a 3-year-11-month-old boy with AGS. The patient was
      anemic with a preoperative hemoglobin of 9.1 g/dl and had mild aortic stenosis
      and mild pulmonary artery stenosis. He underwent living donor liver
      transplantation without blood transfusion. The key points of successful
      anesthetic management included complete pre-operative evaluation of the
      cardiovascular system, and intra-operative maintenance of normothermia, normal
      ionized calcium, normal pH and stable hemodynamics. Surgical blood loss, ascites
      and intraoperative transudate loss were primarily replaced with 5% albumin and
      crystalloids to maintain the central venous pressure around 10 cm H2O. No blood
      transfusion was given for a hemoglobin level higher than 6-7 g/dl, but the
      intravascular volume was sufficient to maintain stable hemodynamics. Our patient
      tolerated the anemia well, it did not seem to affect the recovery of the new
      liver allograft postoperatively.

PMID- 15455547
TI  - Retrograde tibial nail for femoral shaft fracture with severe degloving injury.
AB  - We report an unusual case involving a motorcycle-vehicle collision, in which a 21
      year-old woman sustained severe bilateral lower extremity degloving injuries and
      an associated right femoral shaft fracture. The trauma team was consulted to
      treat this disastrous event. Due to extensive contamination of the open wound
      around the entry site, retrograde intramedullary nailing was chosen to fix the
      fractured femoral shaft in preference to antegrade intramedullary nailing. A
      tibial interlocking nail was used as a substitute for immediate bony
      stabilization to facilitate soft tissue debridement and subsequent
      reconstruction. The excellent range of motion achieved in the right knee joint,
      without infection, limb-length discrepancy, rotational instability or angular
      malalignment, was encouraging.

PMID- 15455548
TI  - Cavernous sinus thrombosis and cerebral infarction caused by Fusobacterium
      nucleatum infection.
AB  - We report an unusual case of fusobacterial infection with secondary intracranial
      invasion. The condition was complicated by a cavernous sinus thrombosis and
      ischemic stroke. The patient was a 63-year-old woman with no history of systemic
      disease who had undergone a tooth extraction before the onset of symptoms. She
      initially suffered from sphenomaxillary sinusitis and a cavernous sinus
      thrombosis, and subsequently developed meningitis. Cerebrospinal fluid
      examination suggested a pyogenic infection. Anaerobic culture revealed
      Fusobacterium nucleatum. However, despite immediate antibiotic therapy, her
      condition remained unstable over the next few days, and she eventually developed
      an ischemic stroke. We describe our experience in the management of this case of
      anaerobic meningitis and the unusual complication of ischemic stroke; this case
      suggests that more aggressive therapy in addition to empirical antibiotics may be
      warranted.

PMID- 15455549
TI  - Mindfulness meditation training combined with eye movement desensitization and
      reprocessing in psychotherapy of an elderly patient.
AB  - We present our experiences with an elderly patient with depression that was
      attributed to a surge of physical ailments who also had trauma-derived fear of
      having to undergo a tracheotomy. He refused pharmacotherapy and was offered
      intensive training in Mindfulness Meditation (MM) plus Eye Movement
      Desensitization and Reprocessing (EMDR) therapy during the 2 weeks of
      hospitalization. This treatment combination had not been used previously. We
      suggest that EMDR eliminated his fear of surgery, whereas MM relieved his
      depression and attendant anxiety. However, the two techniques appeared to work
      synergistically. Following his discharge, he continued to practice MM, which
      prevented the recurrence of emotional distress, and even helped to reduce its
      causative physical symptoms. We offer an explanation for the success of our
      combined treatments and discuss the potential usefulness in specific
      psychotherapeutic situations. We also propose a place for MM within general
      geriatric care, and point out the reluctance to consider the therapeutic value of
      meditation.

PMID- 15455550
TI  - [Basic principles of structural asymmetry of cortex formations in the human
      brain].
AB  - Studying the cytoarchitectonical asymmetry of human brain cortex requires using
      the new approaches and modern quantitative methods. One of the promising ways is
      analyzing relation between the macroscopic and neuronal structure of the brain.
      The present article contains original data of histological and morphological
      studies. The authors develop the concept of different degree of expression of
      asymmetry in the cortex formations of left and right hemispheres. The data on the
      principal differences of topography and types of structure of fissure and gyrus
      in different brain hemispheres are presented. Results of the analysis carried out
      enable one to show the basic criteria of peculiarities of cytoarchitecture of
      human brain cortex in the left and right hemispheres.

PMID- 15455551
TI  - [The mechanisms in NO-dependent regulation of electrical and mechanical activity
      in smooth muscles].
AB  - The role of nitric oxide (NO) and its implication in intracellular and
      intercellular signaling pathways attract an attention of many research teams up
      to now. Away of its signaling functions. NO is considered as one of the key
      molecules in maintenance of balance between the physiological and pathological
      processes due to cytoprotective and cytotoxic functions of this molecule. In this
      regard, elucidation of the NO-dependent mechanisms, involved into the
      physiological processes and pathophysiological reactions, remains an urgent
      problem of conntemporary biology and medicine. Analysis of obtained results
      establishes a relative contribution of electro- and pharmaco-mechanical coupling
      mechanisms in NO-dependent regulation of smooth muscle cels (SMC) functions. The
      authors show that elevation of intracellular Ca2+ concentration by biologically
      active substances promotes relaxing effect of NO through both voltage-dependent
      and -independent intracellular mechanisms of calcium redistribution. Namely the
      peculiarities of considered mechanisms in each certain type of SMCs cause the
      final direction of alterations in contractility and membrane potential. It has
      been shown that voltage-dependent effects of NO are mediated by suppression of
      calcium and/or sodium components and modulation of Ca2+ -dependent and ATP
      seisitive potassium components of SMC membrane permeability, Voltage-independent
      NO control of mechanical smooth muscles activity mainly is mediated by 1)
      modulation of protein kinase C (PK-C) branch of calcium signaling system, 2)
      ratio of cyclic nucleotides intracellular concentrations (cGMP/cAMP), and 3)
      directional mode of electrosilent Na+, K+, 2Cl- -cotransport. Our results show
      that the features of the myogenic effects of NO are caused by the peculiarities
      of PK-C operation in SMC.

PMID- 15455552
TI  - [Characteristic properties of thrombin neurotropic activity].
AB  - There are considered the characteristic features of thrombin functional activity
      in central and peripheral nervous system. A family of specialized membrane
      receptors--so called PARs (Proteinase Activated Receptors) and their presence in
      several parts of CNS is described. The concentration- and PAR-dependent
      neuroprotecting and injuring effects of thrombin in CNS are compared. The
      literature and original authors data are presented demonstrating the presence of
      PARs in peripheral nervous system and the ability of endogenous and exogenous
      thrombin to influence the regeneration of peripheral nerves. The perspectives of
      experimental approach are discussed, when the exogenous thrombin or peptide
      agonists of PARs are used to accelerate the nerve regeneration in vivo.

PMID- 15455553
TI  - [Regeneration of myocardium].
AB  - It has been systematized modern data on the myocardial regeneration and the
      regulation of cardiac cell proliferation in mammals and man. It has been
      performed an analysis published works which indicate that cardiomyocyte division
      and DNA synthesis in myocardial cells increase in many times during different
      pathological conditions. It has been generalized and analyzed results of
      experimental and clinical researches on the participation of stem cells in the
      regeneration of the heart. It has been present literature data on the telomeres
      and telomerase in cardiomyocytes.

PMID- 15455554
TI  - [Steroid hormones: their physiological role and diagnostic value during
      pregnancy].
AB  - Steroid hormones play a key role in the beginning, development and termination of
      gestation. This reveiw is devoted for physiological effects of estrogens,
      progesterone, cortisole, ACTH, CRH in various pregnancy events: implantation,
      fetus development, maternal adaptation and birth initiation. Priority is fixed
      for estrogens--steroids that vastly increase maternal circulating blood value,
      induce progesterone action on uterus, regulate fetal "hypothalamic-pituitary
      adrenocortical" axis, control free cortisole level in feminine blood. Diagnostic
      criterions of steroid hormone determination durijng pregnancy are presented. To
      day unconjugated estriol is the only steroid hormone that implicated in total
      pregnancy screening programs. Its concentration reduction has been noted in
      pregnancies with Dawn syndrome, some child enzyme defetcs, intrauterine growth
      retardation and fetal death incidents.

PMID- 15455555
TI  - [The report on scientific and scientific-organizational activity of Section of
      physiology of Branch of biological sciences RAS in 2003].

PMID- 15455556
TI  - [Neuroendocrinology in the Jubilee Year (on the materials of conference
      "Neuroendocrinology-2003"].

PMID- 15455557
TI  - [Traditional and new problems of physiology (to the discussion about the
      organization of 19-th Congress of Physiologists of Russia)].

PMID- 15455558
TI  - Feeling the pressure? One out of three American adults has hypertension. What you
      need to know.

PMID- 15455559
TI  - Controversial report puts JCAHO under scrutiny: is survey process flawed?

PMID- 15455560
TI  - Handling data: concurrent vs. retrospective approach.

PMID- 15455561
TI  - Are you complying with medical staff standards?

PMID- 15455562
TI  - Evidence-based design could help quality of care.

PMID- 15455563
TI  - How to boost satisfaction rates: a tale of two EDs.

PMID- 15455564
TI  - Are you doing enough to prevent infant deaths?

PMID- 15455565
TI  - Worst practices used in conducting FMEA projects. Part 2 of a two-part series.

PMID- 15455566
TI  - Protecting the wave of the future: establishing security for the electronic
      health record.

PMID- 15455567
TI  - Government issue: CHI lays the groundwork for federal data exchange.

PMID- 15455568
TI  - When the writ hits the fan: the importance of managing electronic health records
      as business documents.

PMID- 15455569
TI  - Anticipating error: identifying weak links in the electronic healthcare
      environment.

PMID- 15455570
TI  - Career opportunities in information technology.

PMID- 15455571
TI  - Overdose of privacy law creates headaches for student health clinics.

PMID- 15455572
TI  - E-environments: highlighting the role of HIM.

PMID- 15455573
TI  - Managing HIPAA as gatekeeper.

PMID- 15455574
TI  - E-HIM strategic initiative: core data sets.

PMID- 15455575
TI  - The case for portable electronic health records.

PMID- 15455576
TI  - Keeping classification in the family: WHO framework assigns systems based on
      numerous factors.

PMID- 15455577
TI  - Physicians cast wary eye at computer-assisted coding.

PMID- 15455578
TI  - HIM director on cutting edge of electronic records.

PMID- 15455579
TI  - Community-based participatory research: an approach to intervention research with
      a Native American community.
AB  - Community-based participatory research (CBPR), with its emphasis on joining with
      the community as full and equal partners in all phases of the research process,
      makes it an appealing model for research with vulnerable populations. However,
      the CBPR approach is not without special challenges relating to ethical,
      cultural, and scientific issues. In this article, we describe how we managed the
      challenges we encountered while conducting a CBPR project with a Native American
      community. We also suggest criteria that will enable evaluation of the project.

PMID- 15455580
TI  - Bridging distance and culture with a cyberspace method of qualitative analysis.
AB  - This article describes a qualitative research method that weds the cyberspace
      technology of e-mail with a phenomenological research approach. Examples are
      provided from 2 separate data sets. One data set explored the meaning of health
      for Japanese elders; the second explored Chinese nurses' experience of taking
      care of patients with severe acute respiratory syndrome. Lessons learned while
      using the cyberspace method are discussed, including guidance for organizing a
      long-distance research team, the central place of trust, and the time when e-mail
      communication demands to be supplemented with face-to-face interaction. The
      potential for bridging distance and culture with this cyberspace method is
      introduced for consideration and critique.

PMID- 15455581
TI  - Faith and feminism: how African American women from a storefront church resist
      oppression in healthcare.
AB  - It is well documented that racism in the US healthcare system, including the
      objectification and disparagement of women of color, contributes to disparities
      in health status. However, it is a mistaken notion to characterize women of color
      as unknowing victims. In this study, black feminist standpoint epistemology is
      used in methodological approach and analysis to understand how a small group of
      African American church-going women use religious beliefs to help them cope with
      and resist the racism and discriminatory objectification they encounter in
      healthcare encounters.

PMID- 15455582
TI  - Pattern, participation, praxis, and power in unitary appreciative inquiry.
AB  - This article is an explication and clarification of unitary appreciative inquiry
      based on several recent projects. Four central dimensions of the inquiry process
      are presented: pattern, participation, praxis, and power. Examples of inquiry
      projects demonstrate and illuminate the possibilities of unitary appreciative
      inquiry. The relationship of these central dimensions to experiential,
      presentational, propositional, and practical knowledge outcomes is articulated. A
      matrix framework integrating pattern, participation, praxis, and power
      demonstrates the potential for generating knowledge relevant to the lives of
      participants and creating an inquiry process worthy of human aspiration.

PMID- 15455583
TI  - Creating a synthesis of intentionality: the role of the bracketing facilitator.
AB  - The role of a bracketing facilitator during the analysis phase of
      phenomenological research is discussed. As a research colleague, a bracketing
      facilitator plays an important part in a fellow researcher's task of uncovering
      his or her constitutive relationship with the research phenomenon. The primary
      task of a bracketing facilitator is providing assistance for a colleague in
      moving away from the usual cognitive mode of thinking during data analysis and
      into a state of emotional sensitivity to personal history and experience of the
      phenomenon. A step-by-step approach to the search for personal connections is
      presented, including an example of the process of facilitating this search. A
      table of guidelines that includes specific points for the act of bracketing as
      well as the content to be bracketed is intended as a tool for the development of
      phenomenological description.

PMID- 15455584
TI  - An improved methodology for advancing nursing research: factorial surveys.
AB  - Clinical judgments and decisions are an integral component of nurse work and
      nurses are increasingly being challenged to account for their judgments and
      decisions. Nursing research is needed to help explain judgment and decision
      making in nursing, but most research in this area is almost exclusively
      characterized by descriptive studies. This article describes the use of the
      factorial survey method, which combines the explanatory power of a factorial
      experiment with the benefits of a sample survey. This hybrid technique is an
      excellent method for studying judgments and decisions across settings, roles,
      disciplines, and countries. This article outlines the steps of the method and
      demonstrates its applicability with an exemplar from a study across nurses from 3
      countries.

PMID- 15455585
TI  - Event analysis techniques.
AB  - Event analysis (EA), a qualitative research technique adapted from the fields of
      anthropology and sociology, can be used to describe and explain social
      interactions and behaviors associated with complicated clinical situations. Event
      analysis is useful in limiting the focus of data collection in complex settings
      and in obtaining and managing multiple perspectives about an event of interest
      while situating the event within appropriate social and environmental contexts.
      This article reviews contemporary uses of EA in clinical nursing research,
      describes the modification and application of EA techniques to common methods of
      data gathering (observation, interview, and document review) in clinical
      settings, and presents recommendations for conducting EA in clinical settings by
      using exemplars from a current study.

PMID- 15455586
TI  - Measuring tuberculosis: lessons from Afghanistan.

PMID- 15455587
TI  - Quality and stability of TB medicines: let the buyer beware!

PMID- 15455588
TI  - Lung cancer epidemiology and risk factors in Asia and Africa.
AB  - In industrialised countries, lung cancer is the most common form of cancer among
      males and it is growing among females. For both sexes, rates reflect smoking
      behaviours. The pattern appears to be different in Asia, particularly in China,
      where lung cancer rates in men reflect high smoking rates but high rates among
      non-smoking women appear to be related to other factors. The incidence of lung
      cancer is low in most African countries, but it is increasing. In addition to
      tobacco smoking, a number of etiological factors have been identified for lung
      cancer: indoor exposure to environmental tobacco smoke, cooking oil vapour, coal
      burning, or radon, outdoor air pollution and occupational exposure to asbestos
      and other carcinogens. Recent studies have shown that dietary factors may be
      important, with high consumption of vegetables and fruits being protective while
      preserved food and fatty food are harmful, and certain infections such as
      Mycobacterium tuberculosis, human papilloma virus and Microsporum canis are
      associated with a high risk of lung cancer. Among non-smokers, the probable role
      of genetic predisposition in lung cancer by increasing the individual's
      susceptibility to environmental carcinogens is currently being studied actively.
      As the single most important cause for lung cancer is tobacco smoke and, with
      increased sales, a major epidemic is predicted for both Asia and Africa, all
      health care professionals, government health authorities and national and
      international health organisations must join in a concerted effort against
      tobacco.

PMID- 15455589
TI  - Implementing joint TB and HIV interventions in a rural district of Malawi: is
      there a role for an international non-governmental organisation?
AB  - In a rural district in Malawi, poorly motivated health personnel, shortages of
      human and financial resources, weak dialogue between existing tuberculosis (TB)
      and human immunodeficiency virus (HIV) programmes and poor community involvement
      are constraints to establishing joint TB-HIV interventions. The presence of a non
      governmental organisation (NGO), Medecins Sans Frontieres (MSF), in the health
      care delivery system provided an opportunity to bridge some of these gaps. The
      main inputs provided by MSF included additional staff, supplementary drugs
      including antiretroviral drugs, technical assistance and infrastructure
      development. The introduction of a scheme of monthly performance-linked
      incentives for health personnel proved successful in improving their performance,
      as judged by attendance rates as well as the quality and quantity of activities.
      This initiative also provided the district management with a tool for exerting
      pressure on health staff to improve their performance. The availability of
      independent NGO funds and a logistics team for construction of new infrastructure
      allowed the rapid initiation of new interventions at the district level without
      having to wait for disbursements of funds from the central level. This introduced
      a new dynamic of decentralised operational flexibility at the district level
      which improved access to care and support for people with TB-HIV.

PMID- 15455590
TI  - A tuberculin skin test survey among Afghan children in Kabul.
AB  - SETTING: Kabul, Afghanistan, October to November 2000. OBJECTIVE: To determine
      the prevalence and the average annual risk of infection with Mycobacterium
      tuberculosis (ARTI). METHODS: A cluster sampling method was selected to carry out
      the survey. Sub-divisions of Kabul's districts were chosen, and door-to-door
      visits were carried out to register the children. The prevalence of tuberculous
      infection was determined using a cut-off point to denote infection and mixture
      analysis. The average ARTI was derived algebraically from the prevalence
      estimates. RESULTS: The tuberculin skin test was administered and read in 89% of
      registered children. Utilising a cut-off point of > or = 8 mm in duration, the
      estimated prevalence of tuberculous infection was 4.3% and the calculated average
      ARTI was 0.61%. Using mixture analysis, the average ARTI was estimated to be
      0.34% (95% credibility interval 0.23-0.54). This indicates a substantial decrease
      from the estimated ARTI of 2.55% calculated in the 1963 survey. CONCLUSIONS:
      There has been a large decrease in the risk of tuberculous infection in Kabul
      since the last assessment. The adverse situation in the past decades does not
      appear to have severely affected the epidemiological situation.

PMID- 15455591
TI  - The physical and chemical stability of anti-tuberculosis fixed-dose combination
      products under accelerated climatic conditions.
AB  - OBJECTIVE: To determine the physical and chemical stability of anti-tuberculosis
      fixed-dose combinations (FDC) of rifampicin (RMP), isoniazid (INH), pyrazinamide
      (PZA) and ethambutol (EMB) sold on the Indian market. METHODS: The products were
      stored for 3 months under ICH/WHO accelerated conditions (40 degrees C / 75% RH),
      with and without the original packaging in the presence and absence of light.
      RESULTS: The initial RMP, INH and PZA content was found to be within the range of
      90-110% of the label claim. However, the products were found to have some
      chemical instability even initially; one of the tablets also showed physical
      instability. Under accelerated conditions, the unpackaged products underwent
      severe changes, whereas both physical and chemical changes were also observed in
      the packaged formulations. The physical changes were stronger under lighted
      conditions. A significant finding is that PZA and perhaps EMB may play a
      catalytic role in the interaction between INH and RMP. CONCLUSION: This study
      suggests that, unless they are packed in barrier packaging, anti-tuberculosis FDC
      formulations should be considered unstable, and due consideration should be given
      to their development pharmaceutics, packaging and stability testing.

PMID- 15455592
TI  - Quality control of anti-tuberculosis fixed-dose combination formulations in the
      global market: an in vitro study.
AB  - OBJECTIVE: To determine the quality, and especially the dissolution properties of
      rifampicin, of fixed-dose combination (FDC) formulations of anti-tuberculosis
      agents manufactured by major market holders in the anti-tuberculosis sector and
      supplied for use in national tuberculosis control programmes. METHODS:
      Dissolution studies were performed for four formulations supplied by four
      different manufacturers in four dissolution media (0.1N and 0.01N HCl, phosphate
      buffer [PB] and 20% vegetable oil in PB), at four different agitation rates using
      USP apparatus II. The formulations were subjected to 4-week accelerated stability
      studies (40 degrees C / 75% RH) and evaluated for physical, chemical and
      dissolution stability. RESULTS: The formulations tested complied with
      pharmacopeial quality control (QC) tests. The extent of rifampicin release was
      independent of dissolution medium; however, a slight decrease in the dissolution
      rate was observed in two products. More than 75% of drug was released in 45 min
      at all agitation intensities except 30 rpm, and 20% oil in the medium reflected
      fed state. Formulations were stable in the packaging conditions recommended by
      the manufacturer for at least 4 weeks. CONCLUSIONS: The formulations tested
      passed the QC tests and were found to be stable. A decrease in the rate, although
      not the extent, of dissolution necessitated multiple point dissolution in gastric
      and intestinal pH conditions to ensure consistency in in vivo bioavailability.

PMID- 15455593
TI  - Auditing the new decentralised oral treatment regimens in Malawi.
AB  - SETTING: All 44 non-private hospitals in Malawi treating tuberculosis (TB) cases
      in which oral regimens were used allowing patients during the initial phase to
      receive directly observed treatment (DOT) from health centres or guardians at
      home. OBJECTIVES: A country-wide audit of the oral regimens to determine: 1) TB
      ward bed occupancy rates, 2) patient DOT options, 3) patients' knowledge of
      treatment and 4) treatment outcomes compared to those obtained with previous
      treatment regimens. DESIGN: Retrospective data collection using registers and
      treatment cards. Prospective interviews with patients. Inspections of TB wards.
      RESULTS: There were 1513 TB beds occupied by 807 (53%) TB patients. Over 50% of
      4793 patients registered with different types of TB chose guardian-based DOT. For
      266 patients with pulmonary TB the correct knowledge about total duration of
      treatment (45%), all three DOT options (62%) and the months for giving follow-up
      sputum (16%), was poor. There were differences in treatment outcomes between TB
      patients on oral compared with previous regimens. With oral regimens, rates of
      unknown outcome were high. CONCLUSION: Oral treatment regimens are associated
      with reduced bed occupancy rates on TB wards. However, rates of unknown outcome
      are increased, and TB control is therefore weakened.

PMID- 15455594
TI  - Design and implementation of relational databases relevant to the diverse needs
      of a tuberculosis case contact study in the Gambia.
AB  - The data requirements of a large multidisciplinary tuberculosis case contact
      study are complex. We describe an ACCESS-based relational database system that
      meets our rigorous requirements for data entry and validation, while being user
      friendly, flexible, exportable, and easy to install on a network or stand alone
      system. This includes the development of a double data entry package for
      epidemiology and laboratory data, semi-automated entry of ELISPOT data directly
      from the plate reader, and a suite of new programmes for the manipulation and
      integration of flow cytometry data. The double entered epidemiology and
      immunology databases are combined into a separate database, providing a near-real
      time analysis of immuno-epidemiological data, allowing important trends to be
      identified early and major decisions about the study to be made and acted on.
      This dynamic data management model is portable and can easily be applied to other
      studies.

PMID- 15455595
TI  - The assessment of patients' health-related quality of life during tuberculosis
      treatment in Wuhan, China.
AB  - OBJECTIVES: To validate the SF-36 questionnaire in a Chinese population and to
      assess the patients' health-related quality of life (HQoL) during tuberculosis
      (TB) treatment. DESIGN: The SF-36 (Chinese version) scores of 102 TB cases before
      treatment, after the initial phase and at the end of treatment were compared with
      those of 103 control subjects. RESULTS: The SF-36 scores were valid (internal
      consistency > 0.4) and reliable (Cronchbach's micro > 0.7). Before treatment, all
      except the role-emotional, social function and mental health scales of the TB
      patients were lower than those of the controls (P < 0.01); the patients' scores
      increased significantly during treatment (P < 0.01). In a stepwise regression
      model, age (P < 0.01, OR 0.95), white blood cell count (P < 0.01, OR 0.92) and
      number of symptoms (P < 0.05, OR 0.99) were associated with the total SF-36
      score. At completion of treatment, sex (P < 0.01, OR 0.25) and haemoglobin (P <
      0.05, OR 0.88) remained at the end of the model. CONCLUSION: The SF-36 scores of
      TB patients are low before treatment, indicating a decline in HQoL, with physical
      scales most affected. However, scores increase over the course of treatment. The
      Chinese version of SF-36 is a reliable tool for monitoring HQoL throughout TB
      treatment.

PMID- 15455596
TI  - The Beijing genotype is emerging among multidrug-resistant Mycobacterium
      tuberculosis strains from Germany.
AB  - SETTING: Germany, 1995 to 2001. OBJECTIVE: To determine the genetic relationship
      of 451 multidrug-resistant (MDR) Mycobacterium tuberculosis strains from Germany
      and to identify strains of the Beijing genotype. DESIGN: All strains were
      analysed using IS6110 fingerprinting and a cluster analysis was performed.
      Clustering of isolates was used as a measure for recent transmission. RESULTS:
      Two hundred and fourteen of 433 strains (49.4%) with more than four IS6110 copies
      formed 46 fingerprint clusters comprising two to 32 patients. Transmission links
      based on classical epidemiological data could be established for 39 cases (18.2%)
      and in 14 clusters (30.4%), and included three cases of exogenous reinfection
      with MDR strains. One hundred and seventy-five strains (38.8%) were of the
      Beijing genotype with an increasing annual proportion from 19.2% in 1995 to 58.3%
      in 2001. About 70% of these patients had an indication of foreign birth, mainly
      the former Soviet Union. CONCLUSION: Transmission of MDR strains seems to be
      contributing to the spread of MDR-TB in Germany, and exogenous reinfection with
      MDR strains must be considered as a possible cause of treatment failure. A high
      proportion of these MDR strains is probably carried over from the former Soviet
      Union, and strains of the Beijing genotype represent an increasing cause of MDR
      TB in Germany.

PMID- 15455597
TI  - Simple, phage-based (FASTPplaque) technology to determine rifampicin resistance
      of Mycobacterium tuberculosis directly from sputum.
AB  - SETTING: Cape Town, South Africa. OBJECTIVE: To evaluate the performance of a
      simple, manual, phage-based test for determining rifampicin (RMP) resistance of
      Mycobacterium tuberculosis directly from smear-positive sputum specimens. DESIGN:
      A comparative study of the performance of the FASTPlaque (phage amplification)
      technology to determine RMP resistance directly from smear-positive sputum
      compared with isolation and the conventional indirect Middlebrook 7H11 agar
      proportion method. RESULTS: The FASTPlaque direct RMP test achieved sensitivity,
      specificity and overall accuracy of 100% (11/11), 100% (134/134) and 100%
      (145/145), respectively, compared with the conventional indirect susceptibility
      test method (resolved data). The FASTPlaque direct RMP test reported results
      within 2 days from receipt of the specimen, while the conventional method took
      between 27 and 103 days (mean +/- SD 33.2 +/- 7.2 days). CONCLUSION: FASTPlaque
      technology applied directly to smear-positive sputum offers performance
      comparable to conventional methods, with results available in 2 days instead of
      weeks to months. The test may form a useful part of DOTS-Plus programmes to
      combat multidrug-resistant tuberculosis, improving patient prognosis and reducing
      ongoing transmission of disease. It does not require specialised equipment,
      making it appropriate for high-burden countries.

PMID- 15455598
TI  - Right heart dysfunction in post-tuberculosis emphysema.
AB  - SETTING: University-affiliated general hospital. OBJECTIVE: To evaluate the pump
      performance of right heart before and after exercise in post-tuberculosis
      emphysema. DESIGN: In patients with post-tuberculosis or primary emphysema
      (similar lung volumes), body plethysmography, arterial blood gas analysis and
      echocardiography were performed at rest and after exercise. Right heart pump
      performance was evaluated with the ejection fraction. RESULTS: At rest, in post
      tuberculosis emphysema, diffusing capacity (mean +/- SE 72.7 +/- 3.9 vs. 91.0 +/-
      7.1% of reference) and right ventricular ejection fraction (57.5 + 1.4 vs. 61.3
      +/- 1.2%) were lower and PaCO2 (42.7 +/- 1.1 vs. 38.6 +/- 0.7 mmHg) was higher,
      while lung compliance, airway resistance, PaO2, and alveolar-arterial oxygen
      difference were not different. After exercise, PaO2 (65.6 +/- 2.8 vs. 80.5 +/-
      3.5 mmHg) and right ventricular ejection fraction (51.2 +/- 2.4 vs. 59.6 +/-
      1.7%) were lower and PaCO2 (47.0 +/- 1.5 vs. 40.9 +/- 1.5 mmHg) was higher in
      post-tuberculosis emphysema, whereas alveolar-arterial oxygen difference was not
      different. PaCO2 and alveolar-arterial oxygen difference increased, and PaO2 and
      right ventricular ejection fraction decreased in post-tuberculosis emphysema,
      while they did not significantly change in primary emphysema. CONCLUSION: In post
      tuberculosis emphysema, the impairment of gas exchange was more serious. Global
      assessment should be focused on right heart dysfunction which might be more
      affected than in primary emphysema.

PMID- 15455599
TI  - Social research as an intervention tool in tuberculosis control.
AB  - Our multidisciplinary project on TB control in the Free State, South Africa, is
      targeting two dimensions for intervention: firstly, patients, to facilitate
      compliance and improve quality of care; secondly, the health care system, to
      identify weaknesses that require remedying and best practices to promote better
      TB control. This communication illustrates how social scientists can contribute
      towards the implementation of interventions related to their research, thus
      influencing TB policy, programme planning and practice more directly.

PMID- 15455600
TI  - Vitamin A levels in sputum-positive pulmonary tuberculosis patients in comparison
      with household contacts and healthy 'normals'.
AB  - OBJECTIVE: To estimate serum vitamin A in pulmonary tuberculosis (PTB) patients
      at the start and end of anti-tuberculosis treatment. DESIGN: Serum vitamin A was
      estimated in 47 PTB patients (pre and post treatment), 46 healthy household
      contacts and 30 healthy 'normals'. RESULTS: Mean serum vitamin A in patients at
      the start of treatment was 21.2 microg/dl, which was significantly lower than in
      household contacts (42.2 microg/dl) and healthy 'normals' (48.1 microg/dl). The
      vitamin A levels in patients increased following treatment. CONCLUSION: The low
      vitamin A levels observed in patients returned to normal at the end of anti
      tuberculosis treatment without vitamin A supplementation.

PMID- 15455601
TI  - Local production of nitric oxide in patients with tuberculosis.
AB  - Nitric oxide (NO), produced by the inducible nitric oxide synthase (iNOS), is
      important in host defence against Mycobacterium tuberculosis in rodents, but the
      presence of high-output NO production in human tuberculosis has been
      controversial. We investigated iNOS and nitrotyrosine (Ntyr) expression in
      pleural (n = 7), pulmonary (n = 5) and lymph node biopsies (n = 5) from
      untreated, newly diagnosed tuberculosis patients. Many iNOS and Ntyr reactive
      macrophages were observed in granulomas, including Langhans giant cells,
      indicating high-output NO production at the primary site of disease in
      tuberculosis.

PMID- 15455602
TI  - The oxygen concentrator: an appropriate technology for treating hypoxaemic
      children in developing countries.
AB  - The World Health Organization (WHO) recommends supplying oxygen in developing
      countries by concentrators because cylinders pose considerable logistic and
      financial problems. This technology was employed to treat children in a hospital
      in Ndioum, Senegal, who met the WHO oxygenation criteria. There were clear
      clinical and financial benefits, but neither the nurses' knowledge of the various
      techniques of oxygen supply nor the maintenance service were satisfactory. The
      use of concentrators should be encouraged in developing countries. A strategy
      including technical training, maintenance and monitoring should be adopted.
      Corrective actions were undertaken in Ndioum, and several concentrators are now
      being used on a regular basis.

PMID- 15455603
TI  - Identification of a familial cluster of pulmonary Mycobacterium bovis disease.
AB  - SETTING: Local public health department. DESIGN: Retrospective review of a
      cluster of three pulmonary Mycobacterium bovis cases occurring in a family, with
      genotyping of M. bovis strains isolated from the family members. RESULTS: The
      genotypes of the M. bovis isolates were identical, as determined by three
      different methods: IS6110 restriction fragment length polymorphism, spoligoytping
      and mycobacterial interspersed repetitive units-variable number tandem repeat
      analyses. CONCLUSION: The identification of three acid-fast bacilli (AFB) smear
      positive pulmonary M. bovis cases, presenting in a single family and caused by an
      identical strain, suggests that person-to-person transmission of this organism
      may have occurred, although infection of one or more family members through
      ingestion of a contaminated dairy product could not be excluded.

PMID- 15455604
TI  - Polymerase chain reaction based detection of Mycobacterium tuberculosis complex
      in lupus vulgaris: a case report.
AB  - Lupus vulgaris (LV), the commonest of all forms of cutaneous tuberculosis, can
      affect the earlobes. Authors present a 20-year-old male patient with LV of the
      left earlobe initially misdiagnosed as pyoderma and treated superfluously with
      antibiotics at different intervals over the last 4 years in another hospital.
      Mycobacteria could not be seen or isolated by stained smears or conventional or
      radiometric culture methods from the skin biopsy specimens. Suspected clinical
      diagnosis of our patient was LV. This was supported by positive polymerase chain
      reaction assay and histological findings. The lesion was treated successfully
      with anti-tuberculosis chemotherapy, further confirming the diagnosis of LV.

PMID- 15455605
TI  - Choosing a research study design and selecting a population to study.
AB  - Epidemiological studies have been standardised into a group of 'designs'. The
      descriptive study describes disease by time, place and person and can develop
      hypotheses about associations between disease and possible determinants. The
      analytic study tests these hypotheses. The cross-sectional study measures the
      disease and determinants at a single point in time. The cohort study identifies
      those within a group with or without a determinant, and observes the occurrence
      of disease in the two groups. The case-control study identifies a group of
      patients with a disease and selects a group of persons from the same population
      who do not have the disease, comparing the presence of a determinant in the two
      groups. The experimental study, a type of cohort study, is one in which the
      investigator 'assigns' the determinant (a treatment) to one subgroup in a
      population and compares the occurrence of a disease between those with and those
      without the determinant. All such studies must ensure that the comparisons made
      have relevance to a defined population. This is done by selecting a
      'representative' sample from that population. Carefully selecting a study design
      and population facilitates the creation of new knowledge while avoiding, as far
      as possible, important errors.

PMID- 15455606
TI  - Is second-line anti-tuberculosis drug susceptibility testing reliable?

PMID- 15455607
TI  - Patient safety and clinical risk management--where do we stand?

PMID- 15455608
TI  - Close association between parathyroid hormone and left ventricular function and
      structure in end-stage renal failure patients under maintenance hemodialysis.
AB  - BACKGROUND: Cardiovascular risk factors are a significant burden in end-stage
      renal disease patients under hemodialysis and are the leading cause of death
      among these patients. The influence of parathyroid hormone (PTH) on myocardial
      function as a toxin of uremia is under more attention and evaluation because of
      growing evidence showing that the effects of PTH on cardiac function may be the
      most serious consequence of secondary hyperparathyroidism in renal failure. In
      this study we determined role of excess PTH in the development of left
      ventricular (LV) hypertrophy as well as LV ejection fraction in patients with end
      stage renal disease under regular hemodialysis. METHODS: This study is cross
      sectional that was done on patients with end-stage renal disease (ESRD)
      undergoing maintenance hemodialysis treatment. For patients, Calcium, Phosphorus,
      Alkaline phosphatase and Intact PTH (iPTH) were measured. Hypertensive patients
      were stratified into stages one to three. Echocardiographies for LV hypertrophy
      and ejection fraction (%) were done and patients stratified into normal, mild,
      moderate and severe LV hypertrophy. RESULTS: The total patients were 73 (F=28
      M=45), consisting of 58 non diabetic hemodialysis patients (F=22 M=36), and 15
      diabetic hemodialysis patients (F=6 M=9). The mean age was 46.5+/-16 years. The
      time on hemodialysis was 21.5+/-23.5 months. The LV ejection fraction (EF%) were
      51+/-8 percent. 'iPTH' of patients was 309+/-349 pg/ml. 'iPTH' of diabetic and
      nondiabetic groups was 234+/-265 pg/ml and 329+/-368 pg/ml respectively. Serum
      alkaline phosphatase was 413+/-348 IU/L. Serum alkaline phosphatase of diabetic
      and nondiabetic groups were 295+/-179 IU/L and 443+/-375 IU/L respectively. Serum
      albumin was 4+/-0.75 g/dl. Serum albumin of diabetic and nondiabetic groups was
      3.6+/-0.7 g/dl and 4.2+/-0.7 g/dl respectively. Significant inverse correlation
      of serum ALP with percent of LV ejection fraction and marginal positive
      correlation of serum ALP with LVH and also marginal correlation of serum iPTH
      with LVH were seen. Also significant inverse correlation between serum iPTH with
      percent of LV ejection fraction in non diabetic heart patients was observed.
      CONCLUSIONS: Adverse effects of secondary hyperparathyroidism on LV function and
      structure in this study show the role of excess PTH in the development of left
      ventricular (LV) hypertrophy as well as low LV ejection fraction in patients with
      end-stage renal disease under hemodialysis which needs more attention to control
      of secondary hyperparathyroidism to reduce the risk of cardiovascular morbidity
      and mortality in dialysis patients.

PMID- 15455609
TI  - Adolescent self reported reproductive morbidity and health care seeking
      behaviour.
AB  - BACKGROUND: Addressing reproductive health issues of women is now on the global
      social agenda in the new millennium. Maternal mortality has long been the only
      indicator of women's health even though reproductive morbidity occurs far more
      frequently and seriously affects women's lives. In this paper, an attempt was
      made to assess the magnitude of self reported gynaecological morbidity unrelated
      to childbearing among the adolescents irrespective of their marital status. The
      paper also explored the determinants of health care seeking behaviour of the
      adolescents for their reproductive ailments. METHODS: Both quantitative and
      qualitative data were collected for this study. Cross sectional study was
      conducted both in rural and urban areas using a multistage cluster sampling
      technique. A nationally representative data on 2883 adolescents irrespective of
      their marital status were analysed. RESULTS: Analysis revealed that a large
      proportion of the adolescents (64.5%) reportedly has been suffering from
      gynaecological morbidity. The most frequent form of morbidity was menstrual
      disorders (63.9%) followed by lower abdominal pain (58.6%), burning sensation
      during urination (46.1%), genital itching (15.5%), vaginal discharge (3.4%) etc.
      Multivariate logistic regression analysis revealed that older adolescents aged 15
      19 years, family income, type of family, type of residence and hygienic practice
      during menstruation appeared to be influencing factors for adolescents
      reproductive morbidity. The results also revealed that about one fifth (18.0%)
      sought health care for their gynaecological ailments indicating that adolescents
      were unaware about their reproductive morbidity (p<0.05). For assessing the
      factors influencing their health care seeking for reproductive morbidity,
      multivariate logistic regression analysis found significant positive association
      with adolescents aged 15-19 years, having autonomy in treatment, working status,
      adolescents of joint or extended family (p<0.05). DISCUSSION: Adolescent
      reproductive health in Bangladesh indicates high incidence of maternal morbidity.
      The incidence of these health problems varied by socio-economic and demographic
      characteristics of the adolescents. Recommendations to address these problems
      include encouragement of female education, introduction of family life education
      in school curricula, creating community awareness for seeking health care and
      empowerment of women in household decision making process.

PMID- 15455610
TI  - Applicability of international prognostic index in non Hodgkin's lymphoma in
      Pakistan.
AB  - BACKGROUND: Aggressive non Hodgkin's Lymphomas (NHL) are common in Southeast
      Asia, Middle East and Africa. Data on survival with relation to prognostic
      factors is scarce. The primary objective of the study was to evaluate the
      applicability of International Prognostic Index (IPI) to predict overall survival
      (OS) and disease free survival (DFS) in developing countries. METHODS: Two
      hundred and nineteen patients of NHL consecutively presenting to the Department
      of Oncology, Jinnah Hospital Lahore between August 1998 to July 2000 were
      analyzed. All patients underwent initial staging according to Ann Arbor staging
      system. The patients were categorized by five independent risk factors: patient
      age, disease stage, serum lactate dehydrogenase (LDH) levels, performance status,
      and number of extranodal sites involved. Patients were divided into three risk
      categories Low (0 or one risk factors), Intermediate (2 risk factors) and High (3
      or more risk factors). RESULTS: According to IPI low risk category comprised of
      15%, intermediate 21% and high 64% of patients, Overall survival (OS) for 2 years
      and 5 years (n=197) was (69%), (51%), (32%) and (64%), (46%), (13%) respectively
      (p=0.0008). Disease free survival (DFS) for 2 years and five years (n=197) was
      (66%), (43%), (34%) and (66%), (43%), (18%) respectively. Age adjusted (60) DFS
      for 2 and 5 years (n=164) was (70%), (45%), (40%) and (63%), (45%) (19%)
      respectively. OS for 2 and 5 years (n=164) was (71%), (52%), (34%) and (64%),
      (46%), (11%) respectively (p=0.0013). CONCLUSIONS: The IPI accurately predicted
      survival in our population. Modification of treatment protocols according to
      specific risk groups will be beneficial to the developing countries with limited
      resources.

PMID- 15455611
TI  - Comparison of survival periods and response in three modes of treatment for Ca
      esophagus at CENAR Quetta.
AB  - BACKGROUND: Esophageal cancer is a fatal disease, with mortality matching the
      incidence. Balochistan province and Afghanistan happen to fall in the "Esophageal
      Cancer Belt". This study was designed to compare survival periods and response in
      three different modes of treatment for cancer of esophagus at CENAR Quetta i.e
      Radiotherapy plus Surgery, Radiotherapy plus Surgery plus single agent
      chemotherapy and Radiotherapy plus Surgery plus combined chemotherapy. METHODS:
      During 1997, 59 patients with histopathological evidence of Ca esophagus were
      referred to CENAR from primary health care centers in Balochistan and
      Afghanistan. These 59 patients were divided into three groups. Group:I (n=22)
      treated by local irradiation plus surgery. Group:II (n=20) treated by local
      irradiation plus surgery plus Single agent chemotherapy i.e 5 florouracil.
      Group:III (n=17) treated by local irradiation plus surgery plus combination
      chemotherapy i.e Cis-Platinum and 5-florouracil. All patients were evaluated by
      endoscopic examination at 2 month intervals. RESULTS: This study of 59 patients
      (mean age 55+/-13 years and male to female ratio of 1:3), shows that 2 year
      survival is 29% and median survival period is 9 month for all the patients. For
      group I, median survival period = 5 month, 2 year survival = 18% and complete
      response = 17%. For group II, Median survival period = 9 months, 2 year survival
      = 30% and complete response = 20%. For group III, Median survival period = 11
      month, 2 year survival = 41% and complete response = 22%. CONCLUSION: This study
      shows that overall survival is poor in cancer of esophagus and combined
      chemotherapy along with surgery and radiotherapy gives better results as compared
      to other two groups. Also single agent chemotherapy plus surgery plus
      radiotherapy give better results than radiotherapy plus surgery.

PMID- 15455612
TI  - Neoadjuvant chemo-irradiation in un-resectable carcinoma of rectum.
AB  - BACKGROUND: Rectal cancer is one of the most frequent gastrointestinal cancers.
      Conventionally surgery is the mainstay of treatment, however after surgery alone,
      local recurrence is high especially in locally advanced rectal cancer, i.e.
      tethered and fixed rectal cancer. This study was conducted to determine the role
      of neo-adjuvant (pre-operative) chemoirradiation in locally advanced carcinoma of
      the rectum to improve resectability, local control and survival. METHODS: Study
      was conducted in Radiation Oncology department of Shaukat Khanum Memorial Cancer
      Hospital and Research Center from May 97-Oct 99. Thirteen patients with
      unresectable/locally advanced adenocarcinoma rectum received neo-adjuvant
      chemoirradiation, 50 Gray to pelvis by box technique on Cobalt-60 machine with
      concomitant 5-Flurouracil 500 mg/m2 for first three and last three days followed
      by abdomino-perineal/low anterior resection. RESULTS: Neo-adjuvant
      chemoirradiation resulted in resectability rate of 92% and clinical down staging
      in 11/13 (84%) patients and pathological complete response in 2/13 (15%) patients
      and a local recurrence rate of 2/13 (15.38%). Non hematological toxicity
      (diarrhea grade 4--15%, erythema grade 3--23%, dysuria grade 1-2--38%) were main
      problems observed during neo-adjuvant chemoirradition. CONCLUSION: Concomitant
      preoperative chemoirradiation for locally advanced rectal cancer is associated
      with considerable clinical and pathological down staging. Tumor resectability is
      improved with potential for improved local control and is relatively safe with
      acceptable morbidity.

PMID- 15455613
TI  - Effect of 90 decibel noise of 4000 hertz on blood pressure in young adults.
AB  - BACKGROUND: Almost every individual dislikes excessive and unnecessary noise.
      Noise exerts various adverse psychological and physiological effects, on human
      body including a rise in blood pressure. METHODS: 117 volunteer medical students,
      aged 18-23 years were exposed to 90 decibel noise of 4000 hertz for 10 minutes,
      produced by audiometer in a sound-proof room. Blood pressure was recorded every
      three minutes. RESULTS: Blood pressure increased during exposure to noise.
      Average rise in systolic blood pressure was 2.462+/-0.532 mm Hg and average rise
      in diastolic blood pressure was 3.064+/-1.047 mm Hg. Blood pressure came to
      resting value within two minutes after stopping exposure to noise in more than
      50% of the subjects. CONCLUSION: Systolic and diastolic blood pressure increases
      due to noise exposure.

PMID- 15455614
TI  - Evaluation of combined effect of verapamil and ranitidine on the volume and
      acidity of carbachol induced gastric secretion.
AB  - BACKGROUND: This study was conducted to observe the effect of H2-receptor
      antagonist Ranitidine and calcium channel blocker Verapamil on the volume, free
      and total acidity of carbachol induced gastric secretion. METHODS: Twenty four
      albino rats of Sprangue Dawley strain weighing 150-200 grams were used. Animals
      were divided into Four groups. After fasting for 48 hours, pylorus of each animal
      was ligated, verapamil 10 mg/Kg, ranitidine 0.5 mg/Kg and carbachol 600 microg/Kg
      body weight were administered intraperitoneally. RESULTS: It was observed that
      ranitidine significantly reduced both the volume and acidity (p<0.001). Similarly
      Verapamil also significantly reduced the volume, free and total acidity when
      compared to carbachol alone. When verapamil was used in combination with
      ranitidine 15 minutes before carbachol, there was further inhibition of volume
      and acidity as compared to ranitidine alone. This reduction was statistically
      highly significant (p<0.001). CONCLUSION: Our study suggests that combined
      therapy of verapamil and ranitidine may have clinical usefulness in the
      management of severe peptic ulcer and Zollinger Ellison Syndrome.

PMID- 15455615
TI  - Effectiveness of combined thoracic epidural and light general anaesthesia in
      patients undergoing non-cardiac thoracic surgery.
AB  - BACKGROUND: The specialty of thoracic anaesthesia has emerged as a scientifically
      based discipline just 30 years back. At the start of the 20th century empyema and
      tuberculosis were the main indications for the thoracic surgery. Later on with
      the introduction of antibiotics lung malignancies were more commonly operated.
      Recent resurgence of tuberculosis and associated medical illnesses put these
      patients in high risk for surgery and anaesthesia, necessitating introduction of
      more skillful approach. The objective of this study was to evaluate the
      effectiveness of combined thoracic epidural anaesthesia and light general
      anaesthesia in patients undergoing non-cardiac thoracic surgery. METHODS: This
      study was conducted at the department of Anesthesia and Intensive care, Pakistan
      Institute of Medical Sciences, Islamabad from 1st Jan 2001 to 31st August 2002.
      Ten adult patients of both sexes of ASA grade I-III, < 68 years of age, who were
      undergoing non-cardiac thoracic surgery were included. Thoracic epidural and
      central venous lines were placed 20 to 30 minutes before the start of procedure.
      All patients received same premedication, induction agents, analgesics,
      inhalational agents and muscle relaxants. All patients were transferred to
      Surgical Intensive Care unit after completion of the procedure. RESULTS: Seventy
      percent patients were operated on lungs, twenty percent on mediastinum and one
      percent for carcinoma of esophagus. Only one patient had co morbid disease of
      hypertension. One patient (10%) died of massive intraoperative hemorrhage. One
      patient (10%) developed superior vena caval obstruction, that was to be operated
      for mediastinal growth. Rest of eight (80%) patients were extubated in the
      operation theatre. All (100%) patients received intraoperative blood transfusion.
      20% patients required additional analgesia in the postoperative period. 20%
      developed postoperative arrhythmias. CONCLUSION: Combined use of light general
      anaesthesia and thoracic epidural is effective in patients undergoing non-cardiac
      thoracic surgery.

PMID- 15455616
TI  - Female surgical sterilization at a tertiary care hospital in Karachi.
AB  - BACKGROUND: Tubal ligation for sterilization is one of the common methods of
      contraception practiced by women in developing countries like Pakistan. This
      study was undertaken to study characteristics of couples undergoing surgical
      sterilization, and to identify ways of improving utililization of contraceptive
      services. MATERIAL AND METHODS: Details of 1148 women who underwent tubal
      ligation at the reproductive health center Jinnah Postgraduate Medical Center
      Karachi from January to December 2002 were recorded on a special proforma. The
      woman's age, duration of marriage, number of living children and the couple's
      educational status were recorded. Contraceptive use and duration, and associated
      medical conditions were documented. Data was entered in SPSS, frequency tables,
      means and standard deviations were obtained and comparative evaluation undertaken
      using non parametric methods, as indicated. RESULTS: Out of the 4210 initial
      clients, 1163 (27.62%) underwent surgical sterilization. This included 1148
      (98.69%) tubal ligations and 15 (1.31%) vasectomies. Of these, 608 (52.96%) were
      carried out in the immediate puerperium. The mean age of women was 33.1+/-3.55
      years, they had been married for 14.84+/-4.22 years and 44.34% had already had 6
      or more children. CONCLUSION: Tubal ligation performed after careful selection
      and counseling, by experienced personnel under local anaesthesia is a safe
      procedure with very few complications. However older women with no history of
      contraception, who have already had 6 or more children, seem to avail it.
      Promotion of temporary contraceptives for birth spacing among younger couples is
      more likely to improve maternal and newborn health in addition to limiting the
      family size.

PMID- 15455617
TI  - Audit of leiomyoma uterus at Khyber teaching hospital Peshawar.
AB  - BACKGROUND: Fibroid is the commonest tumor of the reproductive tract and
      frequently encountered problem in gynecological practice. This study was carried
      out to observe the frequency of fibroids in relation to age, parity and clinical
      manifestations along with a critical review of its management. METHODS: This
      study was carried out over a period of one year from 1st January to 31st December
      2000 in Gynae "A" unit of Khyber teaching hospital, Peshawar. All patients
      presenting with fibroid uterus were included in the study. Data collection
      included age, parity, menstrual pattern, presenting symptoms, medical and
      surgical treatment history. Diagnostic criteria were clinical and
      ultrasonography. Evaluation of medical treatment and surgery were carried out.
      Management outcome of minimal invasive surgery was also observed. RESULTS AND
      CONCLUSION: Total 146 cases were observed. Greater frequency was found in late
      reproductive and perimenopausal years (65.7%). There were 34.2% cases in
      reproductive age group. Majority was multiparous (72%) and 28% were nulliparous.
      Infertility was noticed in 16%. Myomas were mostly symptomatic (70%). Menstrual
      symptoms were commonest (81.5%), pain was second common symptom (27.3%). About
      24% presented with abdominal mass and hyaline degeneration were in 50% of cases.
      Leiomyomas were multiple in 63.1% and commonest variety was interstitial (60.4%).
      Familial factor noticed in 5.4%, clinical diagnosis was made in 58.2% of cases,
      while ultrasound was used in 40.4% of patients, conservative treatment was given
      in 37.6% including medical therapy (8.2%). Surgery was performed in (62.3%).
      Myomectomy (10.2%) and hysterectomy was carried out in 52.05%. Minimal invasive
      surgery was not possible in our set up.

PMID- 15455618
TI  - Magnesium sulphate in the prophylaxis and treatment of eclampsia.
AB  - BACKGROUND: Magnesium Sulphate is considered to be the agent of choice for the
      control of eclamptic seizures in pregnant women. Our objectives were to determine
      frequency of eclampsia and pre-eclampsia in our unit and to determine the effect
      of initial loading dose of magnesium sulphate on maternal and fetal outcome.
      METHODS: This study was carried out in Department of Gynaecology at Lady Reading
      Hospital, Peshawar. In the year 2000 only 133 patients received magnesium
      sulphate out of 228 cases of eclampsia and pre eclampsia due to the problems with
      the continuous supply of the drug. This included 53 cases of eclampsia and 80
      cases of pre-eclampsia. Information regarding the dosage of magnesium sulphate
      labor out come, maternal and fetal outcome, side effects and complications of
      therapy were evaluated from hospital case records. The magnesium sulphate regimen
      consisted of 4 gm loading dose as 20% solution intravenously over 10-15 minutes
      followed immediately by 5 gm into each buttock. Dose of 5 gm intramuscularly was
      repeated only if the patient developed convulsions. RESULTS: Eclampsia and pre
      eclampsia occurred in 1 in 25.5 and 1 in 34.4 deliveries respectively. Majority
      of patients received the initial loading dose of magnesium sulphate, but in 2
      patients' dose had to be repeated. In two patients of pregnancy induced
      hypertension convulsions occurred soon after delivery unheralded by any signs and
      symptoms of impending eclampsia. Perinatal mortality was 19 (35.8%) and 16 (20%)
      in eclampsia and pre-eclampsia respectively. High perinatal mortality was
      attributed to prematurity as only 16.98% of eclampsia and 57.5% of pre-eclampsia
      were more than 37 weeks. One patient of severe pre-eclampsia developed postpartum
      hemorrhage and acute renal failure, but she recovered while another one developed
      sudden postpartum collapse immediately after delivery and died due to
      cerebrovascular accident. 8 patients of eclampsia died despite intensive
      management. All of them were referred from periphery with history of multiple
      fits and were brought in a serious state. CONCLUSION: Frequency of eclampsia and
      pre-eclampsia is high in this region with high perinatal and maternal morbidity
      and mortality. Magnesium sulphate is an effective drug to prevent and control
      seizures. It is easy to administer and subsequent nursing is easy. Seizures
      usually terminate after the initial loading dose of magnesium sulphate.

PMID- 15455619
TI  - Performance of ICT-TB test in the detection of pulmonary and extra-pulmonary
      tuberculosis.
AB  - BACKGROUND: Tuberculosis is a major public health problem of the developing
      nations including Pakistan. We need a simple, economical and non invasive test to
      make an early diagnosis of T.B. in order to avoid the complications. METHODS: A
      study was conducted at the Dept. of Pulmonology, PGMI LRH Peshawar & Ayub
      Teaching Hospital Abbottabad with the collaboration of Dept of Pathology KMC
      Peshawar from Jan 1998 to Dec 2002. A total of 129 patients were included in the
      study. Out of these 129 patients 52 were pulmonary TB (PTB) smear positive, 30
      were PTB smear negative, 30 pleural effusion & 17 were TB lymphadenitis. The
      control group consisted of 25 non TB patients and healthy subjects. RESULTS:
      Antibody was detected in 23 of 52 (44%) sputum positive patients, 11 of 30 (36%)
      sputum negative PTB patients, 10 of 30 (20%) patients of TB pleural effusion and
      6 of 17 (35%) patients of TB lymphadenitis. Antibody was detected in none of the
      control subjects. The overall sensitivity for Pul-T.B. Sputum positive patients
      was 44%, 36% for sputum Negative Pulmonary TB, 20% for TB pleural effusion and
      35% for TB lymphadenitis. The specificity was 100%. CONCLUSION: ICT-TB is a
      highly specific, but less sensitive aid in the diagnosis of Pulmonology and extra
      Pulmonolgy TB.

PMID- 15455620
TI  - Pattern of homicidal deaths in Faisalabad.
AB  - BACKGROUND: Homicide is a reflection of extreme aggression. Many factors
      influence such a behavior. Family environment, urbanization and the presence of
      weapons. We conducted this study on autopsies conducted at the department of
      forensic medicine, Punjab Medical College Faisalabad to know the dimensions of
      homicide in terms of age, sex, weapons involved and seasonal variation if any.
      METHODS: The study encompasses all 188 cases of homicide reporting for autopsy at
      the department of forensic medicine, Punjab Medical College Faisalabad from July
      2001 to June 2002. The cases were categorized on the basis of police inquest and
      autopsy findings. RESULTS: The homicide rate in Faisalabad was 8.3/100,000
      population/year. The age of predilection was the third decade of life and males
      outnumbered females by a ratio of 3.47:1. A firearm was used in almost 50% of the
      cases. A surge in the summer months was noticed. CONCLUSION: Homicide rate is
      high in Faisalabad. Firearms are the major weapon used for committing homicide.

PMID- 15455621
TI  - Screening for biochemical abnormalities in urolithiasis patients.
AB  - BACKGROUND: The significance of biochemical screening in stone formers has been a
      debated topic. This study was conducted to investigate the frequency of
      biochemical abnormalities in our urolithiasis patients and to compare the
      abnormality between the first time and recurrent stone formers so that this
      information would help in assessing the value of biochemical screening in our
      practice. METHODS: Over a twenty-one month period, new and recurrent stone
      disease patients had one random blood specimen and two random 24-hour urine
      collections analysed for biochemical abnormalities. Serum was checked for
      calcium, urate, phosphate and creatinine. The urines were measured for volumes,
      calcium, oxalate, urate, citrate, cystine and pH. RESULTS: Out of total of 113
      patients, 83 (73%) had some urinary or blood abnormality. Highest number of
      abnormalities were in urine. Low volume 33 (39.76%), hypercalciuria 33 (39.76%)
      and hyperoxaluria 20 (24.1%) were the main urinary abnormalities. Elevated serum
      creatinine in 10 (12.05%) was commonest blood abnormality. Females had
      significantly higher frequencies of low urinary volume (48% vs 21%, p=0.001),
      hyperoxaluria (38% vs 11%, p=0.002) and hypocitraturia (37% vs 0%, p<0.001).
      There was no significant difference of abnormality rate between first time and
      recurrent stone formers. CONCLUSION: A high frequency of urinary biochemical
      abnormality and equal abnormality frequencies among first time and recurrent
      stone formers highlights the significance of biochemical screening even in cases
      of initial stone presentation. We feel such diagnostic evaluation would help in
      providing precise treatment and efficient prophylaxis.

PMID- 15455622
TI  - Doctors perception about staying in or leaving rural health facilities in
      District Abbottabad.
AB  - BACKGROUND: An imbalance exists between offered medical services and needed
      health care for the people in rural areas of Pakistan. Many studies have found
      non-availability, of health care providers as major contributors to the poor
      health indicators of the rural areas. METHODS AND RESULTS: An endeavor to attend
      the issue has been made through a cross-sectional survey of the Medical Officers
      working in the different health facilities of District Abbottabad. The study
      found that the doctors are neither trained to work in rural setups nor they are
      given proper facilities and service structure to work there. They perceive to
      face disadvantages affecting their social, professional and family life, if they
      join in rural areas. RECOMMENDATIONS: This study recommends strengthening of
      Community Oriented Medical Education for motivating doctors towards participation
      in rural health services. Doctors working in rural health facilities might be
      given financial and professional incentives and a conducive environment to retain
      them.

PMID- 15455623
TI  - Radiological investigation of dysphagia at D. H. Q. teaching hospital D. I. Khan.
AB  - BACKGROUND: Dysphagia is a common presenting symptom. In most of the cases with
      established dysphagia extensive investigations are required to ascertain the
      cause. A number of advanced diagnostic radiological facilities are available at
      bigger centers, however conventional radiography is the mainstay of radiologist
      in less equipped centers. This study was conducted to have a critical review of
      diagnostic accuracy of conventional radiography at our center. METHODS: This
      study was conducted at Radiology department of DHQ teaching hospital, Dera Ismail
      Khan from 01-01-2001 to 30-06-2002. Available methods of conventional radiography
      including plain radiography neck, lateral view in extension, x-ray Chest P.A. and
      lateral views, Barium/Gastro-grafin swallow-AP and lateral views were used for
      the diagnosis. RESULTS: Out of 100 cases, 35 patients were of Esophageal growth,
      1 case of Esophageal Web, 4 cases of Esophageal Diverticula, 1 case of Corrosive
      Stricture, 1 case of Transverse colon-replacement surgery, 5 cases of Extrinsic
      compression by Cardio-megaly, 1 case of Esophageal Diverticula with growth, 2
      cases of Retropharyngeal abscess, 5 cases of Achalasia, 2 cases of Hiatus
      hernia/gastro-Esophageal reflux, 4 cases of Foreign Bodies in the Esophagus
      Coins/Fish bone, 2 cases of Marked Osteophytosis in the Cervical/Thoracic Spine
      and 1 case of Esophageal Atresia with Tracheo-Esophageal Fistula. The diagnosis
      was no radiological abnormality in 36 cases. CONCLUSIONS: Diagnoses by
      conventional radiography methods is possible in most cases of dysphagia at our
      center, however advanced facilities are required for inconclusive cases.

PMID- 15455624
TI  - A young man with hoarseness of voice.
AB  - A 45 year-old driver presented with a two months history of hoarseness, fever,
      productive cough, anorexia and weight loss. He chewed tobacco. He was previously
      seen and treated without benefit by a family Physician and two ear, nose and
      throat consultants. Crackles were heard in the left scapular region. An X-Ray of
      the chest showed a right apical cavity, perihilar infiltrates and blunting of
      left costophrenic angle. His sputum smear showed acid fast bacilli. A high index
      of suspicion for tuberculosis is recommended while dealing with such cases.
      Complete recovery of patient's voice with anti-tubercular therapy confirmed it
      was a case of laryngeal tuberculosis.

PMID- 15455625
TI  - Boerhaave's syndrome: a diagnostic dilemma in the emergency room.
AB  - Boerhaave's syndrome is a potential lethal condition which presents not only a
      diagnostic but also a therapeutic challenge. Errors in diagnosis are usually
      caused by unawareness of its varied and atypical presentations. All clinicians
      need to be aware of this lethal disease, its frequent unusual presentations and
      the importance of early diagnosis.

PMID- 15455626
TI  - Fallopian tube prolapse after abdominal hysterectomy.
AB  - A 38 year old lady who had total abdominal hysterectomy, for chronic pelvic pain,
      presented with profuse vaginal discharge per vaginum along with a cystic pelvic
      mass of 10 week size. There was a polypoidal fleshy growth present in the vault.
      It was diagnosed to be a fallopian tube on histopathology. Patient was treated
      with bilateral salpingo-ophorectomy through an open laparotomy.

PMID- 15455627
TI  - Experience with beta-blockers in long term management of peripartum
      cardiomyopathy.
AB  - Peripartum cardiomyopathy (PPCM) is an ominous complication of pregnancy, about
      which little is known. Although the role of Beta Blockers is well established in
      heart failure, there is limited data evaluating their use in Peripartum
      cardiomyopathy. We report the use of Beta-Blockers (metoprolol) in conjunct with
      standard heart failure therapy in two patients of PPCM with favorable long-term
      outcome. Our experience, although limited, highlights the significance of use of
      Beta-Blockers in this rare life threatening condition.

PMID- 15455628
TI  - Eccrine porocarcinoma and Bowen's disease with fatal metastasis to the lung.
AB  - The term eccrine porocarcinoma was introduced by Mishima and Morioka in 1969 for
      the malignant counterpart of eccrine poroma. We report an uncommon and a rare
      case of an invasive adnexal carcinoma like porocarcinoma coexisting with Bowen's
      disease with extremely rapid progression, metastatic spread to the lungs, leading
      to death in weeks.

PMID- 15455629
TI  - Actinomycosis in neck glands.
AB  - A middle aged woman presented with right submandibular swelling, fever off and on
      and anemia. Excisional biopsy of the gland showed Actinomycosis. It is a rare
      disease in the neck. Patient was treated with high doses of parenteral pencillins
      followed by three months course of oral Doxycyclines. The patient was followed up
      to six months and she was symptom free. In this case report the disease is
      elaborated and literature is reviewed.

PMID- 15455631
TI  - [Researcher+physician=oxymoron?].

PMID- 15455630
TI  - Body mass index, lipid profile and cardiovascular diseases.

PMID- 15455632
TI  - [Migrants in health care--efficient treatment does exist].

PMID- 15455633
TI  - [SSRI resistant depression. Supplementation with noradrenergic pharmaceuticals
      can be a good alternative].
AB  - About five percent of the Swedes are treated with antidepressants, mostly SSRI:s.
      One third of those are non-responders. In that situation augmentation with a
      noradrenergic drug, such as reboxetine, can be a successful treatment strategy.
      This paper discusses clinical and scientific experiences of combinating SSRI:s
      and NRI:s.

PMID- 15455634
TI  - [Deep venous thrombosis of the lower extremity. Ultrasonography should replace
      phlebography as first line diagnostic imaging].
AB  - In Sweden, there is a widespread use of ascending venography for the diagnosis of
      deep vein thrombosis of the lower extremities (LEDVT) instead of ultrasonography.
      The main reason for this is the inferiority of US in diagnosing LEDVT in the calf
      veins. In order to indirectly estimate the magnitude of this inadequacy, we
      reviewed all of the cases of attempts to perform venograms at our center during a
      four-month period. The results showed that only 4-5 per cent of requested and
      successful venograms were able to show signs of LEDVT in the calf veins (distal
      LEDVT). With regards to these results and a recent report by SBU (Swedish Council
      on Technology Assessment in Health Care), we believe that US with compression
      technique and Doppler should be considered as a replacement for venography of the
      lower extremities as the first line of diagnostic imaging modality.

PMID- 15455635
TI  - [Good experiences with physical therapy in patients with focal dystonia].

PMID- 15455636
TI  - [Acute arthritis].

PMID- 15455637
TI  - [New aspects of Wallenberg syndrome and other brain stem infarctions].
AB  - Studies with MRI and non-invasive vascular imaging have modified previous
      conceptions on clinical spectrum and causes of different types of brain stem
      infarcts. Wallenberg's syndrome caused by lateral medullary infarction (LMI)
      often presents with patterns of sensory loss different from the "classical"
      crossed type. LMI carries a risk for respiratory and cardiovascular complications
      in the acute phase, warranting close patient monitoring. Medial medullary
      infarcts often present with a lacunar syndrome mimicking capsular or pontine
      small vessel disease. Cerebellar infarcts are most often caused by cardiac
      embolism. Isolated vertigo may be the only presenting symptom. Neurosurgical
      intervention of expansive cerebellar infarcts may be life-saving. Clinical
      features of progressive multifocal brain-stem symptoms are often suggestive of
      basilar artery occlusion. CT-angiography is a useful initial diagnostic tool.
      Based on observational studies, intraarterial thrombolysis is used in selected
      patients with basilar artery occlusion, but further studies are needed to define
      treatment criteria more precisely.

PMID- 15455638
TI  - [The man behind the syndrome--Adolf Wallenberg].

PMID- 15455639
TI  - [Scientific fraud--the journals' dilemma].

PMID- 15455640
TI  - [The diabolic syndrome].

PMID- 15455641
TI  - [From research to practice supported by ethical principles].

PMID- 15455642
TI  - [Prehospital CPR must be developed, too].

PMID- 15455644
TI  - [X-ray costs in Lund and Malmo].

PMID- 15455643
TI  - [Vitamins B in Sweden: overprescription, underprescription or wrong
      prescription?].

PMID- 15455645
TI  - Alcohol and mortality from all causes.
AB  - A large number of prospective studies have observed an inverse relationship
      between a moderate intake of alcohol and coronary heart disease morbidity and
      mortality. Concerning death from all-causes, results are not unanimous. Alcohol
      intake was associated with a protection of all-cause mortality in England and USA
      physicians and the large study of the American Cancer Society. None of these
      studies separated the effects of different alcoholic beverages. In our
      prospective studies in France on 35 000 middle-aged men, we observed that only
      wine at moderate intake, was associated with a protective effect on all-cause
      mortality. The reason was that in addition to the known effect on cardiovascular
      diseases, a very moderate intake of wine, protected also from cancer and other
      causes as confirmed by Gronbaek in Denmark. Our recent results also indicate that
      the protective effect of a moderate intake of wine on all-cause mortality is
      observed at all levels of blood pressure and serum cholesterol.

PMID- 15455646
TI  - Risk of dementia and alcohol and wine consumption: a review of recent results.
AB  - The term dementia refers to a clinical syndrome of acquired intellectual
      disturbances produced by brain dysfunction. Dementia may result from a wide
      variety of disorders, including degenerative (e.g. Alzheimer's disease, AD),
      vascular (e.g. multi-infarct dementia), and traumatic (e.g. head injury). Long
      term abuse of alcohol is related to the development of the Wernicke-Korsakoff's
      syndrome or alcohol dementia. However, light to moderate alcohol intake might
      also reduce the risk of dementia and AD. In Bordeaux (France), a population-based
      prospective study found that subjects drinking 3 to 4 standard glasses of wine
      per day (> 250 and up to 500 ml), categorized as moderate drinkers, the crude
      odds ratio (OR) was 0.18 for incident dementia (p < 0.01) and 0.25 for
      Alzheimer's disease (p < 0.03), as compared to the non-drinkers. After adjusting
      for age, sex, education, occupation, baseline cognitive performances and other
      possible confounders, the ORs were respectively 0.19 (p < 0.01) and 0.28 (p <
      0.05). In the 922 mild drinkers (< 1 to 2 glasses per day) there was a negative
      association only with AD. after adjustment (OR = 0.55; p < 0.05). The inverse
      relationship between moderate wine drinking and incident dementia was explained
      neither by known predictors of dementia nor by medical, psychological or socio
      familial factors. These results were confirmed from data of the Rotterdam study.
      Light-to-moderate drinking (one to three drinks per day) was significantly
      associated with a lower risk of any dementia (hazard ratio 0.58 [95% CI 0.38
      0.90]) and vascular dementia (hazard ratio 0.29 [0.09-0.93]). No evidence that
      the relation between alcohol and dementia varied by type of alcoholic beverage
      was found. Stroke constitutes one of the most common causes of serious functional
      impairment in developed countries. Ischaemic strokes represent about 80% of all
      strokes. Several studies have been published and the overall conclusion is that
      heavy drinking is a risk factor for most stroke subtypes. Regular light to
      moderate drinking seemed to be associated with a decreased risk for ischaemic
      stroke.

PMID- 15455647
TI  - Intake of beer, wine and spirits and risk of heavy drinking and alcoholic
      cirrhosis.
AB  - Studies have suggested that wine drinkers are at lower risk of death than beer or
      spirit drinkers. The aim of this study is to examine whether the risk of becoming
      a heavy drinker or developing alcoholic cirrhosis differs among individuals who
      prefer different types of alcoholic beverages. In a longitudinal setting we found
      that both the risk of becoming a heavy or excessive drinker (above 14 and 21
      drinks per week for women and above 21 and 35 drinks per week for men) and the
      risk of developing alcoholic cirrhosis depended on the individuals preference of
      wine, beer or spirits. We conclude that moderate wine drinkers appear to be at
      lower risk of becoming heavy and excessive drinkers and that this may add to the
      explanation of the reported beverage-specific differences in morbidity and
      mortality.

PMID- 15455648
TI  - Moderation in Australia-policy and achievements.
AB  - Alcohol has been consumed in Australia since European settlement in 1788. In
      1998, approximately 60% of Australians consumed an alcoholic beverage at least
      once per week. The effects of alcohol on the human body are dose dependent, where
      the harmful effects of alcohol are generally observed only when alcohol
      consumption exceeds moderate consumption levels of 30 to 40 g of alcohol per day.
      The discovery that a J-shaped curve described the relationship between level of
      alcohol consumption and risk of cardiovascular disease was, however, only made in
      1990-cardiovascular disease is the leading cause of death in the western world.
      Thus prior to 1990, Australian public health policy focused primarily on the
      harmful effects of alcohol consumption and the health benefits of a moderate
      level of alcohol consumption have only recently been recognized in public policy.
      This paper chronicles changes in Australian Federal government policy on alcohol
      since the initial draft National health policy on alcohol in Australia was
      presented to the Ministerial Council on Drug Strategy in 1987 to the National
      Drug Strategic plan for action 2001 to 2003-2004 which was launched in July last
      year.

PMID- 15455649
TI  - Alcohol, wine and platelet function.
AB  - Epidemiological studies have demonstrated an inverse correlation between moderate
      wine and alcohol consumption and morbidity and mortality from coronary heart
      disease. The protective effect has been associated with an increase in the plasma
      level of HDL cholesterol, as it is well recognized that plasma HDL is inversely
      correlated with CHD. In addition, it has become evident that blood platelets
      contribute to the rate of development of atherosclerosis and CHD through several
      mechanisms. In recent studies it has been shown that the level of HDL cholesterol
      can explain only 50% of the protective effect of alcoholic beverages; the other
      50% may be partly related to a decrease in platelet activity. This anti-platelet
      activity of wine is explained by ethanol but also by the polyphenolic components
      with which red wines are richly endowed. Several studies carried out on humans
      and animals have shown that wine phenolics could exert their effects by reducing
      prostanoid synthesis from arachidonate. In addition, it has been suggested that
      wine phenolics could reduce platelet activity mediated by nitric oxide. Moreover,
      wine phenolics increase vitamin E levels while decreasing the oxidation of
      platelets submitted to oxidative stress. However, a rebound phenomenon of
      hyperaggregability is observed after an acute alcohol consumption which is not
      observed with wine consumption. This protection afforded by wine has been
      duplicated in animals with grape phenolics added to alcohol. The rebound
      phenomenon may explain ischemic strokes or sudden deaths known to occur after
      episodes of drunkenness. It appears that wine, and wine phenolics in particular,
      could have a more significant inhibitory effect on platelet aggregation and could
      explain, in part, the hypothesis that red wine is more protective against
      atherosclerosis and coronary heart disease.

PMID- 15455650
TI  - Distinctive effects of red wine and diet on haemostatic cardiovascular risk
      factors.
AB  - The aim of this study was to compare the effects of Mediterranean-type diet (MD),
      high-fat diet (HFD), and red wine supplementation on plasma concentration of
      emergent haemostatic cardiovascular risk factors (HCVRF) and on variables of
      primary haemostasis (bleeding time, plasma von Willebrand factor and platelet
      aggregation/secretion). In a controlled prospective intervention study, two
      groups (21 healthy males each) received either MD or HFD during 90 days. Between
      days 30-60, both diets were supplemented with 240 ml/ day of red wine. After
      adjusting by baseline values, MD was associated with: lower plasma fibrinogen (p
      =0.03), factor VIIc (p=0.034) and factor VIIIc (p=0.0057); higher levels of
      protein S (p=0.013); longer bleeding time (p=0.017); and marginal increases in
      platelet serotonin aggregation and secretion after stimulation with epinephrine.
      Red wine supplementation, in both diets, resulted in decreased plasma fibrinogen
      (p=0.001) and factor VIIc (p=0.05), and in increased t-PA (p=0.01) and PAI-1
      (p=0.0003). The effects of wine on antithrombin III (p=0.01) were divergent:
      there was a decrease in the HFD group but it increased slightly in the MD group.
      No effects of diet or wine were detected in plasma protein C, C-reactive protein
      or von Willebrand factor. BT did not change significantly with wine
      supplementation. Wine intake resulted in a significant increase in ex vivo
      platelet aggregation and secretion after stimulation with collagen (1 and 2
      microg/ml, p < or = 0.01). MD and moderate consumption of red wine have
      complementary, mostly beneficial effects on haemostatic CV risk factors. The
      longer BT in individuals on MD, obtained independently of red wine, denotes less
      interaction of platelets with the vascular wall, which could be beneficial from
      the point of view of CV risk.

PMID- 15455651
TI  - Diet and endothelial function.
AB  - Endothelial dysfunction is one of the earliest events in atherogenesis. A
      consequence of endothelial damage is a lower availability of nitric oxide (NO),
      the most potent endogenous vasodilator. NO inhibits platelet aggregation, smooth
      muscle cell proliferation and adhesion of monocytes to endothelial cells.
      Endothelial dysfunction is present in patients with cardiovascular disease and/or
      coronary risk factors, such as hypertension, dyslipidemia, diabetes, smoking or
      hyperhomocysteinemia. At present, soluble markers and high resolution ultrasound
      of the brachial artery, have provided simple tools for the study of endothelial
      function and the effects of several interventions. It has been demonstrated that
      dietary factors may induce significant changes on vascular reactivity. Nutrients,
      such as fish oil, antioxidants, L-arginine, folic acid and soy protein have shown
      an improvement in endothelial function that can mediate, at least partially, the
      cardioprotective effects of these substances. Attention has been focused on
      dietary patterns in populations with lower prevalence of cardiovascular disease.
      There is some evidence suggesting that Mediterranean diet characterized by high
      consumption of vegetables, fish, olive oil and moderate wine consumption may have
      a positive effect on endothelial function. These results give us evidence on the
      significant role of diet on endothelial function and its impact on the
      pathogenesis of atherosclerosis.

PMID- 15455652
TI  - Inhibitory effects of red wine extracts on endothelial-dependent adhesive
      interactions with monocytes induced by oxysterols.
AB  - Red wine polyphenolic compounds 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 is to examine whether red wine extracts (RWE) can ameliorate
      oxysterol-induced endothelial response, and whether inhibition of adhesion
      molecule expression is involved in monocyte adhesion to endothelial cells.
      Surface expression and mRNA levels of adhesion molecules (intercellular adhesion
      molecule 1 and vascular cell adhesion molecule 1) were determined by ELISA and RT
      PCR performed on human aortic endothelial cells (HAEC) monolayers stimulated with
      7beta-hydroxycholesterol or 25-hydroxycholesterol. Incubation of HAEC with
      oxysterols (10 microM) increased expression of adhesion molecules in a time
      dependent manner. Pretreatment of HAEC with RWE at final concentrations of 1, 10,
      and 100 ng/ml significantly inhibited the increase of surface protein expression
      and mRNA levels. Adherence of monocytes to oxysterol-stimulated HAEC was
      increased compared to that of unstimulated cells. Treatment of HAEC with RWE
      significantly inhibited adherence of monocytes. These results suggest that RWE
      works as an anti-atherogenic agent through the inhibition of endothelial
      dependent adhesive interactions with monocytes induced by oxysterols.

PMID- 15455653
TI  - Red wine administration to apolipoprotein E-deficient mice reduces their
      macrophage-derived extracellular matrix atherogenic properties.
AB  - Proteoglycans (PGs) from the arterial extracellular matrix (ECM) contribute to
      the trapping of LDL and oxidized LDL (Ox-LDL) in the arterial wall, a phenomenon
      called "lipoprotein retention". Moreover, we have shown that subsequent to their
      binding to the matrix, LDL and Ox-LDL are taken up by macrophages. Oxidative
      stress significantly increases macrophage secretion of ECM-PGs, lipoprotein
      binding to the ECM and the uptake of ECM-retained lipoproteins by macrophages.
      The aim of the present study was to determine whether red wine administration to
      atherosclerotic mice would affect their peritoneal macrophage-derived
      extracellular matrix properties, such as the glycosaminoglycan content and the
      ability to bind LDL. In addition, we questioned the ability of LDL bound to the
      mice peritoneal macrophages-derived ECM to be taken up by macrophages. Red wine
      administration to atherosclerotic mice did not affect the mice peritoneal
      macrophages-derived ECM glycosaminoglycan content but it significantly reduced
      the mice peritoneal macrophages-derived ECM ability to bind LDL and the
      subsequent uptake of ECM-retained LDL by the macrophages. The present study thus
      clearly demonstrated the inhibitory effect of red wine consumption by E0 mice on
      their peritoneal macrophage-derived extracellular matrix atherogenic properties.

PMID- 15455654
TI  - Interaction of olive oil phenol antioxidant components with low-density
      lipoprotein.
AB  - Phenolic compounds have shown to inhibit LDL oxidation in vitro and ex vivo;
      however, they are hydrosoluble compounds while LDL is a lipoprotein. Analysis of
      phenolic compounds in LDLs by HPLC is necessary to demonstrate their binding
      capacity to lipoproteins. We developed and validated a solid phase extraction
      method (SPE) that allowed us the purification of LDL samples and their analysis
      by HPLC. This methodology allowed us to demonstrate the in vitro binding capacity
      of tyrosol, one of the main phenolic compounds in olive oil, to LDL. In the
      intervention dietary study with volunteers, food rich in phenolic compounds
      affected LDL composition. Changes in LDL phenolics composition are not observed
      after the short-term ingestion of food rich in phenolic compounds. However, after
      one week of olive oil consumption and Mediterranean diet there was an increase in
      phenolics (p=0.021). An accumulative effect seems necessary to observe
      significative differences in LDL phenolic composition.

PMID- 15455655
TI  - Effect of Mediterranean and Occidental diets, and red wine, on plasma fatty acids
      in humans. An intervention study.
AB  - The type of diet consumed by individuals has been associated with the development
      of some chronic diseases, including cardiovascular disease (CVD), cancer,
      diabetes, and others. Populations that consume diets rich in fruits and
      vegetables and drink wine in moderation, as the Mediterranean, have a higher life
      expectancy and less chronic diseases than other occidental populations. We
      carried out an intervention study in humans to evaluate the effect of a
      Mediterranean diet (MD), an Occidental diet (OD) and their supplementation with
      red wine, on biochemical, physiological and clinical parameters related to
      atherosclerosis and other chronic diseases. For 3 months, two groups of 21 male
      volunteers each, received either a MD or an OD; during the second month, red wine
      was added isocalorically, 240 ml/day. At days 0, 30, 60 and 90, clinical,
      physiological and biochemical evaluations were made. In this article we report on
      the results obtained in plasma fatty acids profile that includes saturated fatty
      acids (SFA), monounsaturated fatty acids (MUFA), polyunsaturated fatty acids
      (PUFA), omega-6 fatty acids, omega-3 fatty acids and omega-6/omega-3 ratio. Other
      results have been published previously. Plasma fatty acid percentages in the OD
      group, compared to the MD group, did not show differences in SFA, but the OD
      group showed lower levels of MUFA and omega-3 fatty acids, and higher levels of
      PUFA and omega-6 fatty acids, with a higher omega-6/omega-3 ratio than the MD
      group. Wine supplementation reduced MUFA and increased PUFA in both dietary
      groups, suggesting that wine could improve a diet with a good omega-6/omega-3
      ratio. Volunteers on MD showed a better fatty acid profile than those on OD,
      suggesting a lower cardiovascular risk. Moderate consumption of wine improves
      this profile in the MD group.

PMID- 15455656
TI  - Omega-3 fatty acids and antioxidants in edible wild plants.
AB  - Human beings evolved on a diet that was balanced in the omega-6 and omega-3
      polyunsaturated fatty acids (PUFA), and was high in antioxidants. Edible wild
      plants provide alpha-linolenic acid (ALA) and higher amounts of vitamin E and
      vitamin C than cultivated plants. In addition to the antioxidant vitamins, edible
      wild plants are rich in phenols and other compounds that increase their
      antioxidant capacity. It is therefore important to systematically analyze the
      total antioxidant capacity of wild plants and promote their commercialization in
      both developed and developing countries. The diets of Western countries have
      contained increasingly larger amounts of linoleic acid (LA), which has been
      promoted for its cholesterol-lowering effect. It is now recognized that dietary
      LA favors oxidative modification of low density lipoprotein (LDL) cholesterol and
      increases platelet response to aggregation. In contrast, ALA intake is associated
      with inhibitory effects on the clotting activity of platelets, on their response
      to thrombin, and on the regulation of arachidonic acid (AA) metabolism. In
      clinical studies, ALA contributed to lowering of blood pressure, and a
      prospective epidemiological study showed that ALA is inversely related to the
      risk of coronary heart disease in men. Dietary amounts of LA as well as the ratio
      of LA to ALA appear to be important for the metabolism of ALA to longer-chain
      omega-3 PUFAs. Relatively large reserves of LA in body fat. as are found in
      vegans or in the diet of omnivores in Western societies, would tend to slow down
      the formation of long-chain omega-3 fatty acids from ALA. Therefore, the role of
      ALA in human nutrition becomes important in terms of long-term dietary intake.
      One advantage of the consumption of ALA over omega-3 fatty acids from fish is
      that the problem of insufficient vitamin E intake does not exist with high intake
      of ALA from plant sources.

PMID- 15455657
TI  - Polyphenols and red wine as antioxidants against peroxynitrite and other
      oxidants.
AB  - The antioxidant capacity of polyphenols (+)-catechin, (-)-epicatechin and
      myricetin, and of different types of red wines (Cabernet Sauvignon, Malbec and
      blended wine) was evaluated by three assays. (a) NADH oxidation by peroxynitrite
      (ONOO-): the ONOO- scavenging activity was higher for myricetin (IC50=35 microM)
      than for (+)-catechin (IC50=275 microM) and (-)-epicatechin (IC50=313 microM).
      (b) Peroxynitrite initiated chemiluminescence in rat liver homogenate: (-)
      epicatechin (IC50=7.0 microM) and (+)-catechin (IC50=13 microM) were more potent
      than myricetin (IC50=20 microM) in inhibiting the chemiluminescence signal. (c)
      Lucigenin chemiluminescence in aortic rings: (-)-epicatechin (IC50=15 microM) and
      (+)-catechin (IC50=18 microM) showed higher antioxidant capacity than myricetin
      (IC50=32 microM). All the assayed red wines were able to scavenge the oxidants
      and free radical species that generate the signal in each assay. Cabernet
      Sauvignon was the red wine with the highest antioxidant capacity in comparison
      with Malbec and blended wine. It is concluded that the use of sensitive
      biological systems (as the aortic ring chemiluminescence) provides important
      information in addition to the results from chemical (NADH oxidation by
      peroxynitrite) and biochemical (homogenate chemiluminescence) assays and offers
      advances in the physiological role of polyphenols.

PMID- 15455658
TI  - A pyranine based procedure for evaluation of the total antioxidant potential
      (TRAP) of polyphenols. A comparison with closely related methodologies.
AB  - A novel procedure for the evaluation of total reactive antioxidant potentials
      (TRAP) is described. The method is based on the measurement of the bleaching of
      pyranine by peroxyl radicals. The addition of the antioxidants produces a clear
      induction time whose magnitude is directly related to the antioxidant
      concentration. A comparison of the values obtained with those reported employing
      closely related methodologies shows that the results are significantly affected
      by the substrate employed to monitor the steady state free radical concentration.
      Possible sources of this dependence are discussed.

PMID- 15455659
TI  - Membrane effects of cocoa procyanidins in liposomes and Jurkat T cells.
AB  - We investigated the effects of the interaction between flavanols and related
      procyanidins (dimer to hexamer) with both cell and synthetic membranes, on
      bilayer fluidity and susceptibility to oxidation. Cocoa derived dimers (0.05 to 1
      microg/ml) protected Jurkat T cells from AMVN-mediated oxidation and increased
      plasma membrane fluidity. These effects occurred in a concentration- and chain
      length-dependent manner. In liposomes, procyanidins prevented the Fe2+ -induced
      permeabilization of the membrane. Together, these results support the hypothesis
      that procyanidins could interact with the polar headgroup of lipids, increasing
      membrane fluidity and also, preventing the access of molecules that could affect
      membrane integrity.

PMID- 15455660
TI  - Antioxidant mechanisms of polyphenolic caffeic acid oligomers, constituents of
      Salvia officinalis.
AB  - Caffeic acid, rosmarinic acid and oligomers of caffeic acid with multiple
      catechol groups are all constituents of Salvia officinalis. Their antioxidant
      potential was investigated with regard to their radical scavenging activity and
      the stability and structure of the intermediate radicals. Pulse-radiolytic
      studies revealed very high rate constants with hydroxyl radicals. Evidence from
      kinetic modeling calculations suggested an unusual complex behavior due to the
      presence of both O4- and O3-semiquinones and formation and decay of a hydroxyl
      radical adduct at the vinyl side chain. The radical structures observed by EPR
      spectroscopy after autoxidation in slightly alkaline solutions were only
      partially identified due to their instability and generally represented
      dissociated O4-semiquinones. Hybrid density-functional calculations of the
      potential radical structures showed distinct differences between the resonance
      stabilization of the O4- and O3-semiquinones of caffeic and dihydrocaffeic acids,
      reflected also in the considerably faster decay of the O3-semiquinone observed by
      pulse radiolysis. No evidence was found for dimerization reactions via Cbeta
      radicals typical for lignin biosynthesis.

PMID- 15455661
TI  - Is the Chilean diet a Mediterranean-type diet?
AB  - Food intake in Chile has changed markedly in the last decades, showing an
      increase in fat consumption and presently a small fruit and vegetables intake. A
      parallel is made between the Chilean and Mediterranean diet (mainly the one from
      Spain, Italy, and Greece), both currently and from 50 years ago. The main
      differences and similarities are based on food availability. Although Chilean
      diet seems to be approaching the traditional Mediterranean diet of the 60's,
      there is concern about changes that are moving away from Chilean traditional diet
      and towards a western one. A new food pyramid for Chile is proposed based on the
      traditional Mediterranean-type diet.

PMID- 15455662
TI  - [Analysis of conditions for different types of enzyme dose response].
AB  - Within the previously described concept designed for a radiation-induced
      activation/inactivation of enzyme tested, an equation for further analysis of the
      dose response changing mechanism has been proposed. This mechanism includes both
      rate and probability of the appearance of different conformation forms of enzyme,
      as well as with accumulation of the water radiolysis active products.

PMID- 15455663
TI  - [DNA-protein cross-links in nuclei and mitochondria of tissue cells from rats of
      various age exposed to gamma-radiation].
AB  - The formation and repair of DNA-protein cross-links (DPC) in the mitochondria and
      nuclei from the brain and spleen of 2- and 29-month rats after their exposure to
      ionizing radiation were studied. The background level of DPC in brain and spleen
      mitochondria of old rats was shown to be about two times as high as in young
      rats. In the nuclei from the brain of old rats the background amount of DPC was
      also increased, unlike the nuclei of spleen of the same rats. At the doses 5 and
      10 Gy (137Cs), the amount of DPC produced in the mitochondria and nuclei of brain
      and spleen of 29-month rats was 1.8-2.5 times greater than in the nuclei of the
      same tissues of young animals. At the same time, in the mitochondria of brain and
      spleen from irradiated rats the amount of DPC was by 30-80% higher than in the
      nuclei of the same tissues. Analysis of changes in DPC content during the post
      radiation period showed that 5 h after irradiation of rats with a dose of 10 Gy,
      the level of these lesions in the nuclei of brain and spleen of young rats
      decreased by 40 and 65%, respectively, whereas the amount of these lesions in the
      mitochondria did not decrease. In this post-radiation period in nuclei of brain
      and spleen of old rats the amount of DPC decreased by 20-40%, respectively.
      However, the data on DPC obtained for the mitochondria of brain and spleen from
      both young and old rats showed that the amount of these lesions did not decrease
      during the 5 h post-radiation period. These results enable the suggestion that
      mitochondria do not possess a system of DPC repair. To summarize, ionizing
      radiation initiates in the nuclei of brain and spleen of old rats more DPC and
      their repair proceeds slower than in the nuclei of the same tissues of young
      animals. In the mitochondria of gamma-radiation exposed old rats more DPC are
      also produced than in young rats but no repair of DPC is observed in both old and
      young animals within the 5 h post-radiation period.

PMID- 15455664
TI  - [Syngeneic and allogeneic immunosupression effects of post-irradiation volatile
      excretions of mice].
AB  - It was shown that immune and olfactory highly reactive CBA mice have reduced the
      ability to immune response in more extent under influence of volatile excretions
      of irradiated (4 Gy) singene mice, than allogene (C57Bl/6) mice. In lowreactive
      C57BL/6 mice deterioration of immune response also took place after influence of
      excretions of singene irradiated mice. There were no difference between the
      effects caused by excretions of intact and irradiated allogene (CBA) mice.

PMID- 15455665
TI  - [Communicative multiplication of secondary disorders in blood formula and
      immunity in groups of intact mice caused by volatile compounds excreted by
      irradiated animals].
AB  - It was shown that immunosupressive substances excreted by the irradiated mice are
      highly volatile. Even the excretion from one irradiated mouse could induce
      disorders in the immune system and blood formula of intact recipients exposed to
      the volatile substances. In turn, a dominate mouse from a group of the exposed
      recipients could cause the disorders in the next intact group. Samples of urine
      from irradiated or exposed to the volatile substances could cause the same
      effect. The experiments showed a mechanism of secondary post-radiation disorders
      in animal groups through volatile chemical signals.

PMID- 15455666
TI  - [Effects of modulators of cytokine levels on mice and rats survival under
      combined radiation/thermal injuries].
AB  - The influence of LPS-induced increasing of proinflammatory cytokine production
      inhibitors (pentoxifylline--POF, glycine--G), Kupffer cells elimination
      (gadolinium chloride--GC) and monoclonal anti-IL-6 antibodies on 30-days
      survival, mean survival time and probability of mortality within animals under
      combined radiation/thermal injury were evaluated. Experiments were carrying out
      on mice (whole body gamma-irradiation at the dose of 7 Gy + 10% body surface full
      thickness thermal burn) and rats (gamma-irradiation at the dose of 7.5 Gy + 15%
      body surface burn). It was established that POF, G and GC didn't modify survival.
      Mouse anti-IL-6 monoclonal antibodies administration 1 h prior and 1, 2, 3 days
      after combined injury increased 30-days animal survival up to 60% in each group
      and up to 90% while antibodies were injected in 6, 7, 8 days after combined
      injuries; 100% lethality was registered in untreated mice. Possible anti
      inflammatory inactivity reasons of modulators of cytokine levels under combined
      injury conditions are discussed.

PMID- 15455667
TI  - [Role of interleukin-6 (IL-6) in the pathogenesis of combined radiation/thermal
      injuries].
AB  - Combined injury such as whole body gamma-irradiation at the dose of 7 Gy+10% body
      surface full-thickness thermal burn were investigated in (CBA x C57BL6)F1 mice.
      Enhanced level of IL-6 in mice serum at 6-24 hs following combined injury was
      established. The potential inhibiting activity of pentoxifylline (POF) as an
      influence to IL-6 levels, and measure of several acute phase response signs has
      been evaluated. It was established, that single POF injection don't modify IL-6
      production, don't change leukocytosis and early hyperfermentemia (as
      alaninaminotransferase levels indicated). But serum albumin content was increased
      after preliminary POF administration to mice with combined injury. On the other
      side, mouse anti-IL-6 monoclonal antibodies administration increased 30-days
      animal survival up to 60% while 100% lethality was registered in untreated mice.
      Possible anti-inflammatory inactivity reasons of POF under combined injury
      conditions are discussed in this article, and important role of IL-6
      hyperproduction in combined injury outcomes burden is suggested.

PMID- 15455668
TI  - [Antiradiation effects of leucynferon on dogs and guinea pigs].
AB  - In experiments with two species of animals (dogs, guinea pigs) irradiated with
      sublethal and lethal doses of gamma-rays, it was observed, that leucynferon had
      antiradiation effect. Course of injections: dogs--8 injections subcutaneus: 2.0
      ml (1, 3, 5, 8, 12, 14, 21, 34 days after irradiation); guinea pigs--14
      injections subcutaneus, 0.2 ml (1-14 days after irradiation). Therapeutical
      effect was explained by capacity of the preparation to defend the hemopoietic
      organs from the radiation and to stimulate hemopoiesis. Leucynferon hindered the
      development of acute radiation sickness symptoms. Immunoreactivity of dogs and
      guinea pigs in experimental group was more complete and restored faster. The
      growth of the automicroflora on the skin was restrained. Production of interferon
      gamma (which is a function of T-lymphocytes) was restored faster.

PMID- 15455669
TI  - [Luplatex and its radioprotective properties].
AB  - In experimental conditions the radioprotective properties of the placental
      complex Luplatex created in Scientific production complex "Biotechindustry" was
      studied. In experiments on mice F1(CBA x C57Bl) it was shown that Luplatex
      injected intraperitoneally in dose 0.5 ml 5-10 min before or after whole body
      gamma-irradiation with 8 Gy (LD80/30) increased the survival up to 40% as
      compared to the control group. In white mice protected by oral administration of
      Luplatex 30 min before exposure to 7.5 Gy, which is absolute minimal lethal dose
      for this type of mice (LD100/30), the effect was 48.3%.

PMID- 15455670
TI  - [239Pu: clinical-cytogenetic description of a case with high radionuclide
      incorporation (24-years of follow-up)].
AB  - This paper describes a case, when large amounts of 239Pu soluble compounds
      penetrated via injured skin and deposited in the skeleton, which resulted in high
      doses from chronic alpha-rays to the red bone marrow. The paper presents a
      pattern of absorbed dose formation over time, status of various organs and
      systems during 24 years of the followup, especially damages in the genome of
      somatic cells using the chromosomal abberation (CA) test in lymphocytes from
      peripheral blood. A high frequency of CA was revealed in the late times of
      clinical follow-up. It was demonstrated that densely-ionizing alpha-radiation is
      characterized by complex symmetrical and asymmetrical chromosomal exchanges and
      multiaberrant cells (MA).

PMID- 15455671
TI  - [On the influence of silicate feeding on metabolism of 137Cs in rabbit].
AB  - The features of 137Cs metabolism in the rabbit's organism when feeding on
      silicates were investigated. By results of two experiments on rabbits
      radiosorption by of zeolite, saponit, humolit, vermiculite and palygorskit in the
      gastrointestinal tract was evaluated. It was found that vermiculite and
      palygorskit had the strongest influence on processes of accumulation and
      decorporation 137Cs, when a dose of additives was 5% of the weight of forage.

PMID- 15455672
TI  - [Adaptive response of blood lymphocytes of the inhabitants of the South Ural
      chronically exposed to radiation].
AB  - The inhabitants of Techa river villages exposed to injured radiation action and
      inhabitants of uncontaminated regions were examined by micronuclei (MN) assay.
      The initial damage of blood lymphocytes, the role of radiation in the induction
      of sensitivity to the acute irradiation and the ability to form the adaptive
      response were evaluated. It was shown that the initial level of damaged
      lymphocytes in the inhabitants of the contaminated area did not differ
      significantly from the spontaneous level. But in these people the sensitivity to
      acute irradiation was decreased. The ability to develop the adaptive response was
      decreased too. It was suggested that the radiation plays the main role in the
      development of radiosensitivity and adaptive response in chronically irradiated
      people.

PMID- 15455673
TI  - [Effect of electromagnetic radiation of millimetric wave band on genome of
      somatic cells].
AB  - The paper presents the characteristic of molecular-genetic processes occurring in
      populations of cells bone marrow, blood, thymus and spleen of animals exposed to
      electromagnetic radiation of millimetric wave band. Disturbances in the processes
      of cell cycle, DNA replication and repair, changes in the frequency of cells with
      micronuclei and cell death by apoptosis mechanism were shown to depend on the
      degree of differentiation and mitotic activity of cells.

PMID- 15455674
TI  - [Influence of Ca2+ ions on UV-induced damage to mice peritoneal macrophage plasma
      membranes].
AB  - It was shown that UV-irradiation caused damage to mice peritoneal macrophage
      plasma membranes. A decrease in extracellular Ca2+ leads to a decrease of the
      damaging effect. An increase in extracellular Ca2+ or adding of calcium ionophore
      A23187 to the medium is accompanied by an increase in a number of damaged cells.
      These data allow us to suppose that modification of the damaging effect of UV
      irradiation by Ca2+ ions can be bound with changing of electric stability of
      membrane lipid matrix.

PMID- 15455675
TI  - [Influence of intracellular pH on character of mice peritoneal macrophage
      response to red light irradiation].
AB  - It was detected that exposure of macrophages to red light (600-740 nm) led to the
      changes in their intracellular pH and hydrolytic activity. The character of these
      changes depends on the initial level of pH in the cells. The maximum effect of
      irradiation is detected if the initial pH level is low. It is possible that Na/H
      exchanger takes part in normalizing effect of red light on intracellular pH
      level.

PMID- 15455676
TI  - [Cytogenetic characteristics of seed offspring of leafy tree plants from one
      kilometer zone of Novovoronezh nuclear power station].
AB  - Cytogenetic characteristics (mitotic activity, level and spectrum of pathological
      mitoses, nucleoly characteristics) of seed offspring of Quercus robur L. and
      Betula pendula Roth from Novovoronezh nuclear power station's 1-kilometer zone
      have been studied. It has been shown the change of time of passing though mitotic
      stages by cells, the increasing of bridges frequency occur in spectrum of mitotic
      aberrations (that shows activation of reparation systems), the change in nucleoly
      characteristics (the part of polynucleolaris cells increase in case of oak and
      decrease in case of birch, the rase of surface square of single nucleolies). The
      phenomena, mean above, probably, induced by synergic effects of Novovoronezh
      nuclear power station and environment pollutants. The most contaminated
      territories of 1-kilometer zone of Novovoronezh nuclear power station have been
      discovered by means of methods of cluster analysis of total cytogenetic
      characteristics of tree plants seed offspring.

PMID- 15455677
TI  - [137Cs vertical migration in boggy soils in the long term after the Chernobyl
      accident].
AB  - 137Cs vertical migration in boggy soils has been studied 15 years after the
      Chernobyl accident. The rate of vertical migration of the radionuclide is shown
      to be dependent on the peculiarities of formation of peatbogs, their moistening
      regime and soil properties. 137Cs migration in a high-land peatbog is
      characterized by higher intensity then in lowland or transitional peatbogs.
      Differences in 137Cs vertical migration are to a large extent caused by the
      contents in soil of exhangeable and mobile radionuclide forms. The derived
      experimental data that describe 137Cs distribution over the profiles of peaty
      soils of different type are used for parameterization of two-component convective
      diffusion model. Ecological and effective half-life periods of 137Cs content
      reduction in the soil root layer have been calculated. A long-term prediction is
      given of the dynamics of the radionuclide content in the root layer of peaty
      soils.

PMID- 15455678
TI  - [Modelling of long-term radionuclide migration in a non-running fresh-water
      reservoir].
AB  - A mathematical model is presented for radionuclide migration in a non-running
      fresh-water reservoir that takes into account removal of microimpurities from
      water as a result of both molecular and ion exchange sorption at the bottom
      sediments water interface and detritus formation. The model was tested for
      sensitivity to precisely estimate experimental parameters. The test showed that
      the model is universal. Prediction was made of reduction in water of 137Cs and
      90Sr contents and distribution of these radionuclides in the water body affected
      by the accident at the "Mayak" chemical plant.

PMID- 15455679
TI  - [Horizontal migration of 137Cs with water erosion of soils].
AB  - The results of research of horizontal migration of 137Cs with soils water erosion
      are presented. It was found that quantitative parameters of 137Cs migration
      depended on radioactive pollution of cultivated soil layer, volume of water
      erosion of soils and character of usage of sloping lands. Activity of 137Cs in
      lower parts of slopes was 37-295 kBq/m2 higher than in the middle and apex parts
      of slopes. Increase in 137Cs activity varied from 10 to 18 percent in
      accumulation zone as compared to outwash zone with soil losses 5.0 t/ha and from
      17 to 35 percent with soil losses 5.1-10.0 t/ha and from 30 to 127 percent with
      soil losses 10. 1-20.0 t/ha.

PMID- 15455680
TI  - [Studies of radioactivity in the ores and mineral products].
AB  - Mineral ores and products made of them were studied by gamma-spectrophotometry.
      Regularities of radionuclide content in ores and products were found. A
      possibility of deactivation of ores and mineral products by the technology of
      aerohydrodynamic concentration was shown.

PMID- 15455681
TI  - [On hygienic and ecological approaches in radiation protection].
AB  - In this paper the problem of substantiation of one of the basic radiation
      protection ensurance principle is considered: sufficiency of a man radiation
      safety ensuring for guaranteed ensuring of radiation safety of the environment
      living components. This paradigm formulated in ICRP recommendations and is often
      referred to as hygienic or anthropocentric approach to environment radiation
      protection is laid down the basis of all national, including Russian, regulations
      in the field of radiation safety. During the last 5-10 years a lot of papers have
      been published, in which the hygienic principle of environmental safety ensuring
      is considered as a matter of dispute and the certain logical basis and the
      quantitative comparative estimations of human exposure doses and most irradiated
      vulnerable parts of nature doses are given. Change of one of the main radiation
      protection paradigms will demand for resolution of the enormously difficult and
      labor-consuming scientific problems. In the present paper, on the basis of
      UNSCEAR models of critical population groups dose formation and consistent
      application of conservativeness principle it is shown that for the ground
      ecosystems today there is no strong reasons for refusal of a hygienic radiation
      protection principle for benefit of ecological one.

PMID- 15455682
TI  - [Virological and immunological indices in patients with multiple sclerosis].
AB  - The level of specific antibodies to viruses of measles, parotitis, type-6 herpes,
      Epstein-Barr, tick-borne encephalitis and Borrelia burgdorferi as well as
      presence of genetic samples and antigens of the above infectious antigens were
      studied in patients with multiple sclerosis (MS). The cytokines Th1 and Th2
      parameters were investigated in blood serum of patients at different MS stages.
      The titer of antibodies to measles virus was noted to be increasing in MS
      patients with age and disease aggravation. The level of antibodies to any of the
      studied infectious agents, except for the type-6 herpes virus, was not
      dynamically changing for as long as 9 months. The viral genetic samples (measles
      RNA) were detected just once in 2 patients; the detection time coincided in both
      cases with MS aggravation. The cytokines dynamics failed to correlate with MS
      aggravation or exacerbation while the total index of all studied cytokines was
      decreased. A high MMPw 9 content in blood serum correlated with MS exacerbation
      in 1 patient.

PMID- 15455683
TI  - [Functional activity of peritoneal macrophages in experimental Ebola fever].
AB  - The phagocytic activity of peritoneal macrophages (a representative of
      mononuclear phagocytes) as well as the TNF-alpha were studied in animals with
      different susceptibility to Ebola virus (EV). The results denote the following:
      1. Phagocytosis activation by peritoneal macrophages after EV is introduced into
      the body correlates directly with a susceptibility degree of an animal to EV. 2.
      The EV content in peritoneal lavage is inversely dependent on a phagocytic
      activity of peritoneal macrophages. The TNF-alpha activity increases, in blood
      serum of body susceptible to EV, 500-fold versus the unsusceptible body.
      Therefore, production of endogenous TNF-alpha can be interpreted as the
      development of body's immune protection but not as a reason for the development
      of vascular shock. Presumably, the nonspecific immunity factors condition the EV
      susceptibility.

PMID- 15455684
TI  - [A new setup for the generation and studies of mono-disperse microbiological
      aerosols in medical-and-biological research].
AB  - A setup for the generation and studies of mono-disperse microbiological aerosols
      is described in the paper. Coefficients of 3 microm aerosol deposition in the
      respiratory tract of mice and rats were refined by using the above setup. The
      probability of deposition of such particles in the trachea and lungs of mice was
      proven to be equal to 1.2 +/- 0.1% and 2.6 +/- 0.2%, respectively. The
      probability for rats was equal to 3.2 +/- 0.2 and 11.8 +/- 0.9%, respectively.
      The distribution of deposited aerosol particles was determined by electron
      microscopy.

PMID- 15455685
TI  - [Pulmonary cell susceptibility in mice and rats to influenza virus when infected
      in vivo and in vitro].
AB  - The purpose of the case study was to evaluate comparatively the relative
      contribution of cell susceptibility and the inhibiting effect of factors of
      pulmonary epithelial lining in mice and rats to influenza virus A/Aichi/2/68
      (H3N2) adapted to mice as related with the development of infection process in
      the lungs of experimental animals when infected in vivo and in vitro. Mice and
      rats were infected aerogenically with different doses of influenza virus. The
      primary cell-culture suspensions sampled from the lungs of mice and rats were
      used to study the adsorption and dynamics of influenza virus production in
      infection by different dose of influenza virus in vitro. The cell suspensions
      were shown to be able to produce the influenza virus for as long as 48 hours
      after infection. It was for the first time that the results denoted the identical
      susceptibility of primary pulmonary cells in mice and rats to influenza virus. A
      lower pulmonary susceptibility to influenza virus in rats versus mice could be
      indicative of that the surface factors of epithelial lining contribute
      essentially to shaping the pulmonary susceptibility to influenza virus since
      there is no difference of the susceptibility of pulmonary cells to influenza
      virus between the two above animals' species.

PMID- 15455686
TI  - [A study of neutralizing activity and cross-reactivity of monoclonal antibodies
      to ectromelia virus with orthopoxviruses pathogenic for man].
AB  - An extensive collection of 125 rat hybridomas secreting monoclonal antibodies
      (Mabs) to ectromelia virus (EV) polypeptide (Poxviridae family, Orhtopoxvirus
      genus) was set up. A significant portion of Mabs (37 types) recognized epitopes
      of the 14 kDa polypeptide as well as the 37 and 35 kDa polypeptides. However, a
      majority of Mabs interacted with conformation-dependent epitopes, which were
      destroyed in immunoprecipitation. One hundred and thirteen of Mabs cross
      interacted with antigenic determinants of vaccinia viruses (VV), cowpox virus
      (CPV) and smallpox virus (SPV); only 12 of them were found to be specific to EV.
      The Mabs antigenic activity was tested for 46 types of cross-reactivity Mabs in
      VV neutralization on Vero cells. Only the 112H12, 113D5, 113F8, 122H9 and 125G9
      Mabs, which were specific to the kDa 14 polypeptide (gene A30L EV), had the
      neutralizing activity. The 122H9 and 125G9 Mabs were able to neutralize SPV.
      Therefore, it can be assumed that the 14 kDa polypeptide carries, on its surface,
      cross-reactivity neutralizing epitopes typical of orthopoxviruses.

PMID- 15455687
TI  - [Human mini-antibodies to orthopoxviruses].
AB  - A library of human scFv antibodies displayed on the surface of bacteriophages
      (MRC, Cambridge, England) was panned against the Elstree strain of vaccinia virus
      (VACV), which resulted in the phage repertoire enriched with clones positive to
      the strain. Individual clones from the repertoire were screened for binding,
      independently, to the vaccinia and ectromelia viruses; phage antibodies to the
      orthopoxviruses were selected. Ten unique antibodies were identified after their
      Vh- and Vl-genes were sequenced. All selected antibodies were assayed by ELISA
      for binding to the vaccinia, cowpox and ectromelia viruses. Furthermore, all
      selected antibodies were assayed for binding with major alastrim strains of the
      live variola virus. According to the results, the above phage antibodies
      recognized genus-specific epitopes, some of which differed in their conformation.

PMID- 15455688
TI  - [Effects of the dsRNA interferon inducer on the interaction between macrophages
      and Mycobacterium tuberculosis in vitro].
AB  - Effects of the IFN inducer, yeast dsRNA, produced on the interaction between
      mouse macrophages and phagocytized mycobacteria were experimentally studied in
      vitro. Mycobacteria were shown to reproduce in macrophages in their initial
      infection at a ratio of 1:1.25, 1:2.5, 1:5 and 1:10, which was confirmed by an
      increased insertion of 5.6-[3H]-uracil in M. tuberculosis H37Rv; they also had a
      destructive impact on macrophages as verified by a higher release of lactic
      dehydrogenase (LDG) from macrophages. The dsRNA preparation, 40.0, 80.0 and 120.0
      microg/ml, was demonstrated to decrease the insertion amount of labeled uracil in
      phagocytized mycobacteria at a macrophage:mycobacteria ratio of 1:10 and 1:100.
      The effect depended on a preparation dose and infection degree of macrophages. A
      decreased release of specific LDG from infected macrophages was shown under the
      same conditions. The dsRNA affects the interplay of macrophages and phagocytized
      mycobacteria through inhibiting the vitality of intracellular mycobacteria and
      through enhancing the stability of macrophages. Special studies denoted that
      dsRNA, 40.0 microg/ml and 120 microg/ml, activated the production of peroxidation
      compounds by neutrophils, which phagocytized the sheep erythrocytes. Finally, a
      possible mechanism of dsRNA impact on the interaction between macrophages and
      mycobacteria phagocytized by them is under discussion.

PMID- 15455689
TI  - [Monoclonal antibodies to recombinant human laminin-binding protein. Production
      and immunochemical description].
AB  - Thirteen murine hybridoma lines producing monoclonal antibodies (Mabs) to
      recombinant human laminin-binding protein (rLBP) were developed. All 13 Mabs
      reacted with affinity purified 43 kDA rLBP in ELISA and Western blotting. Mab
      class determination showed 9 Mabs as belonging to IgM class, 2 Mabs--to IgG2
      subclass, 1 Mab--to IgG1 and 1 Mab--to IgG2b. Ten Mabs of different classes were
      capable to react with LBP on the surface of Vero cells. Mabs displayed a high and
      simultaneously varying affinity to rLBP (10(8) 10(9) M(-1)). The Mab affinity was
      found to be comparable with the mean affinity of mouse and rabbit antibodies
      isolated from hyperimmune sera. The possibility of using the produced Mabs in
      mapping the LBP domains involved in virus attachment, cell differentiation and
      cancer metastases progression as well as in the systemic response to bacterial
      protozoan and parasitic infection is under discussion.

PMID- 15455690
TI  - [Application of peptide phage libraries for obtaining peptides specific to mouse
      lung adenocarcinoma].
AB  - Peptides binding, in vivo, with mouse lung adenocarcinoma, were selected from a
      peptide phage library containing above 100 million of different permutations. The
      selected phages carrying specific peptides accumulated in the tumor node, after
      intravenous injections made in A/Sn mice with induced adenocarcinoma, and
      persisted there even in 24 h after injections; whereas, they were detected in
      small quantities or not detected at all in other tissues (e.g. lungs and
      muscles). The selected bacteriophages were shown to accumulate not only in the
      primary tumor node but also in the lung with multiple metastases. Finally, amino
      acid sequences of exposed peptides were defined.

PMID- 15455691
TI  - [Designing of a liquid serum panel containing or not class IgG antibodies
      specific to human cytomegalovirus].
AB  - Designing of a liquid serum panel for the determination of class G antibodies
      specific to human cytomegalovirus (HCMV) is under discussion. Sera were selected
      by ELISA for antibodies to HCMV and by PCR for CMV DNA. The serum panel comprises
      samples of positive and negative sera with high and low titers. Sera were
      stabilized by a stabilization solution. The panel shelf life was evaluated by
      routine methods and by the "accelerated aging" technique. Sera selected for a
      standard panel containing or not antibodies to HCMV preserve their properties and
      stability for as long as 1 year at 4 degrees C.

PMID- 15455692
TI  - [Amplification test-systems in the diagnosis of hemorrhagic fever with renal
      syndrome and in studies of viral pathogens].
AB  - The "VectoHantivirus-ampli" test system based on rtPCR was shown as fitting the
      detection of virus RNA in blood samples of patients with hemorrhagic fever with
      renal syndrome (HFRS) made at early stages and no later than 7 days from the
      disease onset. A sequence analysis of viral nucleotide sequences of PCR products
      produced by the test-system ensured the identification of Hantaviruses (pathogens
      of HFRS). Two genetic variants of Puumula virus were shown to circulate in the
      territory of the Bashkortostan Republic; they differ by 10.0-13.8%, one of them
      is absolutely new. The Hantan virus FE genetic variant was detected in the
      studied samples from the Khabarovsk Territory.

PMID- 15455693
TI  - [Neuroimmunopathologic aspects of epilepsy].
AB  - The neuroimmune aspects of epilepsy pathology are analyzed in the survey. The
      pathogenetic role of proinflammatory cytokines and of antibodies to neuroagents
      as well as of antibodies to the NMDA-receptor and glutamate was defined within
      the development of epilepsy. It is for the first time that the data of the
      authors' independent research are presented, which testify to the anti-epilepsy
      activity of antibodies to the glutamate.

PMID- 15455694
TI  - [Chronic intestinal pseudoobstruction syndrome in adults].
AB  - The aim of this paper is to debate, based on medical literature review, the
      chronic intestinal pseudoobstruction syndrome in adults, from the surgical point
      of view. The beginning of the paper emphasizes the difficulties in
      pseudoobstruction syndrome definition and etiology, and then we discuss the
      importance of intestinal histological assessment (whenever it is possible) and
      intestinal structure modifications. A very important part of this paper is
      reserved to the diagnostic difficulties, especially to those between intestinal
      pseudoobstruction syndrome and mechanical intestinal obstructive syndrome
      (similar etiologic circumstances, similar clinical and radiological
      manifestations). Finally, this paper debates the therapeutic difficulties,
      emphasizing the importance of surgical methods and techniques useful in treatment
      of the patient with chronic intestinal pseudoobstruction syndrome.

PMID- 15455695
TI  - [Surgical treatment in ulcerative rectocolitis . Analysis of a 24 years
      experience of 50 patients].
AB  - Ulcerative colitis (UC) is an inflammatory bowel disease that may be cured by
      surgery being indicated for emergency situations resulting from complications of
      fulminant disease and for elective indications. We analyzed the last 24 years
      experience regarding 50 patients surgically treated for ulcerative colitis in the
      Center of General Surgery and Liver Transplantation of Fundeni Clinical
      Institute. The indications for surgery were: failure of medical treatment in 22
      patients, acute disease with complications in 20, chronic complications in 8
      cases. We used the following surgical procedures: total proctocolectomy in all 2
      cases with associated rectal cancer, total colectomy with ileo-rectal anastomosis
      (one staged or two staged procedures) in 31, and restorative proctocolectomy in
      17 cases (in all cases as a 2 or 3 staged procedure). In acute disease with
      complications we have performed total colectomy with terminal ileostomy, closure
      of the rectal stump, or exteriorization of the sigmoid stump in a mucous fistula.
      The gravity of acute complications does not justify the use of palliative
      procedures such as ileostomy, colostomy or Hartmann procedure because the
      mortality rate of these operations is higher than the postoperative mortality
      rate of total colectomy performed in emergency. Even in the elective surgery,
      when the patients are in a poor condition, nutritionally depleted, taking large
      doses of steroids or immunosuppressive drugs, we prefer the staged procedure.
      Total proctocolectomy is performed only in the cases of ulcerative colitis
      associated with rectal cancer, severe perianal disease, sphincter incontinence.
      Total colectomy with ileo-rectal anastomosis is indicated when the rectal stump
      has minimal inflammatory lesions. Restorative proctocolectomy is the surgery of
      choice for UC, the functional results being comparable with those of total
      colectomy with ileo-rectal anastomosis, but having the advantage of curing the
      disease. The global mortality rate was 12% (6 patients).

PMID- 15455696
TI  - [Ovarian cancer--diagnostic dilemmas and unusual therapeutic response].
AB  - The aims of this paper are both to highlight some dilemmas concerning the
      diagnosis of primary epithelial ovarian carcinoma mainly in its early stages and
      to underline the capricious responses of this type of malignancy to an otherwise
      well coded modern management. This study is based on the analysis of the records
      of 78 patients with ovarian carcinoma admitted for diagnosis and surgical
      treatment to the Department of General Surgery of Craiova C.F.R. Clinic from 1993
      through 2003. The results of this analysis are difficult to interpret due to loss
      to follow up (in terms of response rates) of some of our 78 operated on ovarian
      carcinoma patients who went on with their platinum-based chemotherapy (following
      surgical cytoreduction) under the supervision of different Oncology Departments
      nationwide. Nevertheless, it is worth mentioning that most of this study patients
      (71.9%) presented with advanced-stage (III and IV) ovarian carcinoma which
      sometimes seemed quite confusing by its clinical polymorphism but its prognosis
      was very much related to both the degree of surgical cytoreduction accomplished
      and tumor sensitivity to chemotherapy. Finally, although this study does not
      allow us to draw firm conclusions it is an attempt to share out our current
      perception on the primary epithelial ovarian cancer management.

PMID- 15455697
TI  - [Hyperthyroidism and coexistent thyroid carcinoma].
AB  - The association between thyrotoxicosis and thyroid cancer is a classical, rare
      and controversial entity. Within their series of eleven such cases the authors
      dissociate two distinct groups from clinical and pathological viewpoint. The
      first category is represented by one case of follicular thyroid cancer with
      clinically and biologically confirmed hyperthyroidism. The second group includes
      ten patients with thyrotoxicosis (three cases with Graves' disease, four with
      toxic multinodular goiter and three with toxic adenoma) and associated
      unsuspected occult or nodular carcinoma. None of these patients had received
      previous treatment with radioiodine. In all cases the diagnosis was established
      by pathological examination of the surgical specimen. Surgery is the treatment of
      choice in these lesions, the presence of carcinoma imposing the extent of
      operation. Five near total thyroidectomies and three near total lobectomies with
      ablation of the isthmus was performed in our cases associated with appropriate
      additional measures: TSH suppression or 131I treatment. Post surgical results
      were satisfactory without morbidity or mortality. The long-term survey was good
      (seven cases alive after 5 years).

PMID- 15455698
TI  - [The complications of colostomies].
AB  - The evaluation of the frequency of complications that arise after colostomies
      performed for colorectal and genital neoplasm, and also the treatment
      possibilities for these complications. In Coltea Hospital, Surgical Department
      during 1984-2002 there have been admitted and surgically treated 891 patients
      with colorectal cancers, among which, 484 had rectosigmoidal neoplasm. We have
      treated 25 patients with complicated genital neoplasm (19 rectovaginal and recto
      bladder-vaginal fistulas following cervical cancers, 5 pelvic tumoral blocks
      following ovarian cancers and a vulvar cancer with local invasion). For all these
      patients we performed: 25 Hartmann resections, 75 Reybard resections, 73 Dixon
      resections and 147 rectal amputations, with 294 colostomies (30 iliac anus in
      continuity-Audrey, 18 on a stick, 232 terminal and 14 cecostomies for protection
      or decompression). There were 48 complications following the colostomies: 10
      cases of stenosis, 14 prolapses, 7 intestinal loop necroses and 17 parastomal
      hernias, all of them surgically managed. Terminal colostomies and colostomies for
      protection are still frequently used in surgical departments, having strict
      indications. Because they are frequently performed as emergencies, at patients
      with poor biological status they are often enough followed by complications, most
      of them with little gravity. The complications can be avoided by a proper
      therapeutic choice and in most cases can be managed with a surgical intervention.

PMID- 15455699
TI  - [Extraperitoneal transomphalic drainage of the posthydatid hepatic restant cavity
      by coelioscopic approach].
AB  - Being often biliary contaminated and suppurative, the hydatid hepatic cyst is in
      fact a real parasitic abscess. So far its surgical approach represents the only
      credible possibility of treatment. Authors impart their experience regarding the
      external drainage of the restant posthydatid cavity, by using a completely
      extraperitoneal way of bringing out the drain, by means of the round ligament, an
      original method conceived and put into practice by Prof. D. Burlui in 1968. This
      technique is simple, without risks or complications, possible for most of the
      parasite hepatic locations, especially for the central segments, for which this
      method is superior to other surgical procedures. The greatest advantage of the
      extraperitoneal transomphalic route of the drain is the absence of the peritoneal
      losses and so the impossibility of biliary leakage occurrence. The radiological
      and the ultrasonic controls confirm the reduction and finally total fibrosis and
      disappearance of the remaining cavity, about two months after the surgery. In
      this moment the drainage may be suppressed. In December 2001, we added to this
      method an other original variant: the coelioscopic approach of the
      extraperitoneal transomphalic drainage of the restant posthydatid cavity,
      representing the aim of this paper.

PMID- 15455700
TI  - [Laparoscopic pseudocysto-jejunostomy].
AB  - Laparoscopic surgery of the pancreas, acquisition of the recent years, finds
      application in the surgical management of pancreatic pseudocysts (PP). Among
      internal drainage procedures that can be performed through laparoscopic approach,
      the pseudocysto-jejunostomy technique (PJS) can be performed using only the
      standard laparoscopic instrument set. We submit the technique we used in
      performing a PJS on three patients admitted in our clinic. The postoperative
      outcome was favorable, having obtained identical results to those of the open
      approach. The mean duration of the interventions was 216.6 minutes. The mean
      postoperative hospitalization was 7 days. The laparoscopic approach allows
      internal drainage of PP in the form of PJS to be performed in good circumstances,
      also bringing about all the specific benefits of this type of surgery.

PMID- 15455701
TI  - [Hydatid cyst--rare presentations].
AB  - Hydatid disease is an parasitic infestation due to germens from Echinococcus
      family, principal localizations of the disease being hepatic and pulmonary. We
      present two cases of disease, first localized primary on the buttock and second
      with multiple organ involving. We consider these cases interesting because of
      rarity and complexity of lesions.

PMID- 15455702
TI  - [Acute diffuse peritonitis of a rare cause].
AB  - The authors report a rare case of acute onset of non-Hodgkin lymphoma with
      diffuse peritonitis due to bowel perforation of secondary jejunal involvement.
      The admission diagnosis in the 18-years-old male with acute abdominal pain for 4
      days, guarding on physical examination and pneumoperitoneum on abdominal
      ultrasonography was peptic ulcus perforation. The palpable splenomegaly and
      cervical lymph nodes on ultrasonography examination might have raised suspicion
      of lymphoma. Surgical exploration revealed the peritonitis origin--jejunal
      perforation, proximal to a stenosing tumor, a gastric tumor and confirmed the
      splenomegaly. Small bowel resection--end to end anastomosis--and gastric tumor
      biopsies were performed. The pathological diagnosis was diffuse large B-cell non
      Hodgkin lymphoma. Some therapeutic considerations on digestive tract secondary
      lymphoma are made.

PMID- 15455703
TI  - [Acute surgical abdomen produced by an abdominalized infected gigantic hydatid
      cyst].
AB  - We report the case of a 47 year old female patient, transferred urgently to our
      clinic with suspicion of a broken liver hydatid cyst, with acute, generalized
      peritonitis. Intraoperative we found a gigantic liver hydatid cyst, surrounding
      the liver with a massive abdominal extension till the Douglas's bottom sack,
      adhesive to the parietal and visceral peritoneum. There are presented particular
      aspects concerning the uncertainties that happened in positive diagnosis
      establish, the disease evolution, as well as the difficulties of surgical conduct
      in this case.

PMID- 15455704
TI  - Critique of the American Cancer Society Guidelines for Breast Cancer Screening:
      Update 2003.
AB  - The American Cancer Society Guidelines for Breast Cancer Screening: Update 2003
      was obtained through the National Guideline Clearinghouse Web site and was
      critiqued for potential incorporation into practice. The updated guidelines
      address screening mammography, physical examination, and new technologies and
      describe how these may be applied to women at average risk, women at high risk,
      and older women. The new guidelines emphasize educating women and having them
      take a more active role in decision making.

PMID- 15455705
TI  - Obesity in youth: implications for the advanced practice nurse in primary care.
AB  - PURPOSE: To discuss the advanced practice nurse's diagnosis and management of
      obesity in youth in primary care. DATA SOURCES: Review of current scientific
      literature, practice guidelines, and a case study. CONCLUSIONS: Obesity in youth
      is difficult to manage. Recent research suggests a genetic and environmental
      etiology associated with impaired glucose tolerance, type 2 diabetes,
      hypertension, hyperlipidemia, and hypertriglyceridemia. Nutrition education,
      increasing physical activity, decreasing sedentary behaviors, and behavioral
      modification have been used with varying success. Management is directed at
      healthy lifestyle behavior change for youth and their families. IMPLICATIONS FOR
      PRACTICE: If obesity, impaired glucose tolerance, hypertension,
      hypercholesterolemia, and hypertriglyceridemia are left untreated, youth may
      develop type 2 diabetes and coronary artery disease later in life and suffer
      early morbidity and mortality.

PMID- 15455706
TI  - Central obesity and the metabolic syndrome: implications for primary care
      providers.
AB  - PURPOSE: To describe screening measures that will determine which clients are at
      risk for the metabolic syndrome, common manifestations of the syndrome,
      preventive diagnostic considerations, and management and treatment options that
      primary care providers can implement. DATA SOURCES: Review of the clinical and
      research literature, supplemented with specific diagnostic criteria. CONCLUSIONS:
      Central obesity is the cornerstone of the metabolic syndrome, which may lead to
      type 2 diabetes and cardiovascular disease. Generalized obesity is defined as
      body weight that is considerably greater than the ideal weight and that is
      distributed on all parts of the body. Generalized obesity has long been
      considered a significant risk factor for developing type 2 diabetes and
      cardiovascular disease. Those clients of ideal body weight have been considered
      at less risk for developing these conditions. However, this perception may not
      always be accurate. Weight distribution plays a major role in acquiring the
      metabolic syndrome. Because waist circumference is as important as overall body
      weight, central obesity is key to determining the risk. IMPLICATIONS FOR
      PRACTICE: The metabolic syndrome has now been given a CPT code (277.7). It is
      more likely that clients at risk for or with the metabolic syndrome may first be
      seen by a primary care provider. Primary care providers need to be able to
      diagnose, treat, and provide preventive interventions for the metabolic syndrome.
      Clients at risk will likely be identified during routine health screening. Early
      detection of and interventions focused on the metabolic syndrome may reduce the
      occurrence of type 2 diabetes and cardiovascular disease. Use of a tape measure
      to determine waist circumference may help the provider to identify at-risk
      clients who are of normal weight, and thus not previously believed to be at risk,
      as well as those more obviously at risk. It is necessary to determine not only
      patients' overall body weight but also their waist circumference. A measuring
      tape may be the key tool for establishing a patient's early risk for the
      metabolic syndrome and, ultimately, for prevention of type 2 diabetes and
      cardiovascular disease.

PMID- 15455707
TI  - Nurse practitioners' and physicians' care activities and clinical outcomes with
      an inpatient geriatric population.
AB  - OBJECTIVE: Less is known about nurse practitioners' (NPs') effectiveness in acute
      care than about their effectiveness in outpatient settings. This study
      investigated care activities and clinical outcomes for hospitalized geriatric
      patients treated by NPs compared with those treated by intern and resident
      physicians. DATA SOURCES: A descriptive comparative research design involved
      random selection of 100 inpatient geriatric patients and a convenience sample of
      17 professional providers who staffed three hospital units. A 1-month study
      period produced retrospective and prospective data for analysis. CONCLUSIONS:
      Self-reports concerning 10 primary activity categories indicated that NPs spent a
      higher percentage of time doing progress notes and care planning than did
      physicians (28% versus 15%, p = .011) and that physicians spent more time on
      literature reviews (5% versus 1%, p = .008). When prioritizing care activities,
      NPs ranked advance directive discussion higher than did physicians (2nd versus
      7th, p = .036), a difference confirmed by medical record documentation.
      Physicians were more attentive to functional status (1st versus 3rd, p = .023),
      but medical record documentation showed NPs to be more attentive to physical and
      occupational therapy referrals (p = .001). Analysis of 13 independent organ areas
      revealed that NPs cared for more musculoskeletal (p = .036) and psychiatric (p =
      .005) problems. Physicians cared for more cardiac patients (p = .001). NPs'
      patients were older (p = .022) and sicker at admission (p < .001) and discharge
      (p < .001). Charges per length of stay were lower (p < .001) for the physician
      provider group, and patients in that group had shorter stays (p < .001).
      Readmission and mortality rates were similar. IMPLICATIONS FOR PRACTICE: NPs
      provide effective care to hospitalized geriatric patients, particularly to those
      who are older and sicker.

PMID- 15455708
TI  - Clinical evaluation and patterns of chemotherapy-induced peripheral neuropathy.
AB  - PURPOSE: To determine the pattern of change in peripheral nerve function (as
      measured by vision, hearing, deep tendon reflexes, vibratory sense, cutaneous
      sensation, gait and balance, muscle strength, and orthostatic blood pressure)
      occurring among individuals receiving cancer treatment with known neurotoxic
      agents. DATA SOURCES: A convenience sample of 16 participants with cancer who
      were receiving chemotherapy had their peripheral nerve function assessed at
      baseline and at 4 weeks and 12 weeks of treatment. Data were analyzed using plots
      and regression slopes to determine change over time in clinical measures of
      peripheral nerve function. Outcome variables were vision, hearing, deep tendon
      reflexes, vibratory sense, cutaneous sensation, gait and balance, muscle
      strength, and changes in orthostatic blood pressure. CONCLUSIONS: This is the
      first prospective study to use comprehensive clinical measures of peripheral
      nerve and muscle changes resulting from combination chemotherapy or a biotherapy
      regimen. Alterations in vision, hearing, deep tendon reflexes, vibratory sense,
      cutaneous sensation, balance, muscle strength, and orthostatic blood pressure
      were noted, but gait remained unchanged. IMPLICATIONS FOR PRACTICE: This study
      provides beginning evidence of the need for careful, ongoing assessment of
      treatment-induced peripheral neuropathy. Standardized clinical practice
      procedures that incorporate patient evaluation for peripheral neuropathy must
      still be developed. In addition, we must educate our patients about the
      functional changes they may expect, and we must develop strategies to assist them
      in managing limitations that they experience as a result of peripheral
      neuropathy.

PMID- 15455709
TI  - Attitudes of registered nurses toward nurse practitioners.
AB  - PURPOSE: Registered nurses (RNs) work closely with nurse practitioners (NPs) in
      all facets of patient care and often have a direct influence on the patient's
      perception of the professional who is directing the care, and a patient's
      perceptions may affect clinical outcomes. However, few studies have been
      conducted to measure RN acceptance of the NP. The authors surveyed RNs in
      southern Illinois to assess their attitudes concerning the level of care provided
      by NPs. Southern Illinois was chosen because of the limited number of NPs in the
      area and because of concerns that limited exposure might negatively influence RN
      attitudes about the NP role. DATA COLLECTION: A 26-item research questionnaire,
      previously used with school nurses, was modified to reflect RNs in general. Seven
      items related to demographic information, and 19 items created a five-response
      Likert-formatted scale (r = .93). The questionnaire was mailed to 500 randomly
      selected RNs from the 11 southernmost counties of Illinois. CONCLUSIONS: The
      results showed support of the NP role. RNs believed that NPs were knowledgeable,
      competent health care providers. RNs were also comfortable working with NPs and
      often consulted them for advice and information. They saw the role of the NP as a
      positive addition to the health care team. IMPLICATIONS FOR PRACTICE: One
      identified concern was that scores indicated RNs felt that they received limited
      respect from NPs. Although the scores were high in this category, some RNs had
      concerns that NPs might not respect or understand the difficulty of the RN role
      in providing patient care. NPs need to recognize their collegial and professional
      ties to RNs and should take time to provide positive feedback to RNs as they
      collaborate to provide health care. Such behavior would only solidify the health
      team approach.

PMID- 15455710
TI  - [Extracellular factors of bacterial adaptation to unfavorable environmental
      conditions].
AB  - Data on extracellular compounds of bacteria involved in their adaptation to
      unfavorable environmental conditions are reviewed, including high or low
      temperatures, growth-inhibiting or bactericidal concentrations of toxic
      substances (oxidants, phenols, and heavy metals) and antibiotics, deviation of pH
      values from optimum levels, and salinity of the medium. Chemically, the compounds
      identified belong to diverse types (proteins, hydrocarbons, organic acids,
      nucleotides, amino acids, lipopeptides, volatile substances, etc.). Most of them
      remain unidentified, and their properties are studied using biological testing.
      It is proposed to view extracellular adaptation factors (EAFs) as a new group of
      biologically active substances. EAFs may be divided into several subgroups by the
      mechanism of action. These subgroups include protectors (stabilizers), signaling
      molecules inducing defense responses, regulators (e.g., adhesion regulators) not
      acting as inducers, and antidotes (neutralizers). The fields of EAF study include
      screening (search for new compounds, using biological tests), identification, and
      research into mechanisms of action. EAFs may find utility in biotechnology,
      medicine, agriculture, and environmental protection.

PMID- 15455711
TI  - [Inhibition of urease by cyclic beta-triketones and fluoride ions].
AB  - Competitive inhibition of soybean urease by 11 cyclic beta-triketones was studied
      in aqueous solutions at pH 7.4 and 36 degrees C. This process was characterized
      quantitatively by the inhibition constant (Ki), which showed a strong dependence
      on the structure of organic chelating agents (nickel atoms in urease) and varied
      from 58.4 to 847 microM. Under similar conditions, the substrate analogue
      (hydroxyurea) acted as a weak urease inhibitor (Ki = 6.47 mM). At 20 degrees C,
      competitive inhibition of urease with the ligand of nickel atoms (fluoride anion)
      was pH-dependent. At pH 3.85-6.45, the value of Ki for the process ranged from
      36.5 to 4060 microM. Three nontoxic cyclic beta-triketones with Ki values of
      58.4, 71.4, and 88.0 microM (36 degrees C) were the most potent inhibitors of
      urease. Their efficacy was determined by the presence of three >C=O- groups in
      the molecule and minimum steric hindrances to binding with metal sites in soybean
      urease.

PMID- 15455712
TI  - [A study of the adhesive glycoprotein-inactivating protein from mammalian blood
      serum].
AB  - A protein with a molecular weight of 70 kDa was isolated from bovine blood serum
      and purified to a homogenous state. This protein inhibited reversibly the
      adhesive serum glycoprotein with a molecular weight of 12 kDa, which displayed
      biological activity at ultralow doses. Amino acid analysis showed that the
      protein inactivator belongs to the group of prealbumins from vertebrate blood
      serum. The secondary structure of its molecule was characterized by a
      considerable number of alpha-helices. The conditions for inactivation of serum
      glycoprotein were studied. The interaction between the serum glycoprotein and the
      protein inactivator occurred over a long period of time (1 day). It should be
      emphasized that the presence of calcium ions was a necessary condition for the
      inactivation of the serum glycoprotein. The data suggest that inactivation of
      serum glycoprotein results from the formation of a molecular complex consisting
      of the protein inactivator and the glycoprotein, which is related to the carbon
      protein interaction.

PMID- 15455713
TI  - [Bromoacyl analogues of phosphatidylcholine with intramolecular fluorescence
      quenching and their use as substrates for continuous monitoring of phospholipase
      A2 activity].
AB  - Two new derivatives of phosphatidylcholine with intramolecular fluorescence
      quenching were obtained by substituting residues of pyrene butyric and bromine
      containing fatty acids for acyl chains. The two compounds can be used for
      quantitative evaluation of catalytic activity of pancreatic phospholipase A2 in
      kinetic mode.

PMID- 15455714
TI  - [Formation of DNA complexes with actinomycins in aqueous solutions and films].
AB  - The mechanisms of DNA interaction with actinomycin D (AMD), 7-amino-actinomycin D
      (7-AAMD), and ethidium bromide (EtBr) were studied in aqueous solutions and in
      condensed state (films coating plates). The use of the methods of absorption (UV,
      IR, and visible spectral ranges) and fluorescence (steady-state, polarization,
      and phase-modulation) spectroscopy revealed that (1) the formation of DNA
      complexes with 7-AAMD in solution was not accompanied by energy transfer from
      photoexcited nucleotides to phenoxazone chromophore and (2) the mechanism of
      ligand incorporation was distinct from stacking. In the film of the DNA-7-AAMD
      complex, which simulated the native state in a biological cell, the efficiency of
      the energy transfer was high. This indicates that a stacking-type mechanism
      underlies actinomycin intercalation into DNA. In the presence of high
      concentrations of 7-AAMD in the film, DNA denatured and its double-helical
      structure, degraded. In the DNA-AMD complex, the native B-form of DNA molecule
      was conserved both in films and in solution.

PMID- 15455715
TI  - [Hydrolysis of heparin by the immobilized enzymatic complex from Streptomyces
      kurssanovii].
AB  - The possibility of obtaining low-molecular-weight heparins using the chitinolytic
      enzymatic complex immobilized on Silochrom has been demonstrated. The optimal
      conditions of this process (sodium acetate buffer, pH 7.0-7.5; temperature, 40-45
      degrees C; and duration of hydrolysis, 3 h) were determined. Depending on the
      ratio between heparin and the immobilized enzymatic complex, samples with
      molecular weight varying from 1.7 to 4.7 kDa, were obtained. These complexes
      inhibited factor Xa in 2.0-3.7 times more effectively than original heparin.

PMID- 15455716
TI  - [Hydrolysis of peptides by immobilized bacterial peptide hydrolases].
AB  - The feasibility of hydrolysis of a mixture of peptides with an enzyme from the
      bacterium Xanthomonas rubrilineans, displaying a peptidase activity and
      immobilized on aluminum oxide, was studied. Kinetic schemes and equations
      allowing for approaching quantitative description of peptide hydrolysis in
      complex mixtures containing free amino acids and peptides were obtained. It was
      demonstrated that as a result of hydrolysis, the content of free amino acids in
      hydrolysates decreased 2.5- to 3-fold and the molecular weight of the constituent
      peptides, 2-fold.

PMID- 15455717
TI  - [Effect of iron hydroxide on the phosphate elimination during anaerobic digestion
      of active sludge].
AB  - Addition of iron (III) hydroxide during methanogenic digestion of active sludge
      by anaerobic sludge displaying an iron-reducing activity resulted in a microbial
      reduction of iron (III) with formation of iron (II), capable of precipitating
      phosphates. Feasibility of eliminating 66.6 to 99.6% of dissolved phosphate at
      initial concentrations of 1000 to 3500 mg PO4(3-)/l by adding 6420 mg/l iron
      (III) hydroxide into a reactor for anaerobic fermentation of active sludge. The
      optimal ratio of iron (III) added to dissolved phosphate eliminated (mg)
      providing a 95% elimination amounted to 2:1. These results may be used in a new
      technology for anaerobic wastewater treatment with phosphate elimination.

PMID- 15455718
TI  - [Effect of cultivation conditions on the growth and activities of sulfur
      metabolism enzymes and carboxylases of Sulfobacillus thermosulfidooxidans subsp.
      asporogenes strain 41].
AB  - The moderately thermophilic acidophilic bacterium Sulfobacillus
      thermosulfidooxidans subsp. asporogenes strain 41 is capable of utilizing
      sulfides of gold-arsenic concentrate and elemental sulfur as a source of energy.
      The growth in the presence of S0 under auto- or mixotrophic conditions was less
      stable compared with the media containing iron monoxide. The enzymes involved in
      oxidation of sulfur inorganic compounds--thiosulfate-oxidizing enzyme,
      tetrathionate hydrolase, rhodonase, adenylyl sulfate reductase, sulfite oxidase,
      and sulfur oxygenase--were discovered in the cells of Sulfobacillus grown in the
      mineral medium containing 0.02% yeast extract and either sulfur or iron monoxide
      and thiosulfate. Cell-free extracts of the cultures grown in the medium with
      sulfur under auto- or mixotrophic conditions displayed activity of the key enzyme
      of the Calvin cycle--ribulose bisphosphate carboxylase--and several other enzymes
      involved in heterotrophic fixation of carbonic acid. Activities of carboxylases
      depended on the composition of cultivation media.

PMID- 15455719
TI  - [Microorganisms of Lake Baikal and Lake Nyasa as indicators of anthropogenic
      influence: prospects of use in biotechnology].
AB  - Restriction endonucleases (RENs) were detected in 650 microbial strains isolated
      from water columns and bottom sediments of deep rift lakes, Baikal (Russia) and
      Nyasa (Southeastern Africa). They enzymes included unique (Fan I, Aca I, and Sse
      91) and very rare (Bsi I, and Cci N I) species not typical of aquatic ecosystems.
      Water columns, deep cores, and bottom sediments of pure areas of the lakes
      contained no microorganisms with new RENs. Thus, inshore areas of Lake Baikal
      exposed to anthropogenic influence may contain mutant bacterial strains
      expressing RENs that have not been described previously.

PMID- 15455720
TI  - [Carotenoids and fatty acids in red yeasts Sporobolomyces roseus and Rhodotorula
      glutinis].
AB  - Rhodotorula glutinis and Sporobolomyces roseus, grown under different aeration
      regimes, showed differential responses in their carotenoid content. At higher
      aeration, the concentration of total carotenoids increased relative to biomass
      and total fatty acids in R. glutinis, but the composition of carotenoids
      (torulene > beta-carotene > gamma-carotene > torularhodin) remained unaltered. In
      contrast, S. roseus responded to enhanced aeration by a shift from the
      predominant beta-carotene to torulene and torularhodin, indicating a biosynthetic
      switch at the gamma-carotene branch point of carotenoid biosynthesis. The overall
      levels of total carotenoids in highly aerated flasks were 0.55 mol-percent and
      0.50 mol-percent relative to total fatty acids in R. glutinis and S. roseus
      (respectively), and 206 and 412 microg g(-1) dry weight (respectively).

PMID- 15455721
TI  - [Effect of 5-azacytidine on the light-sensitive formation of sexual and asexual
      reproductive structures in wc-1 and wc-2 mutants of Neurospora crassa].
AB  - Under the conditions of nitrogen starvation, illumination by blue light of wc-1
      and wc-2 mutants of the ascomycete Neurospora crassa failed to stimulate the
      formation of protoperithecia and inhibit conidiation (contrary to what was
      observed in the mycelium of the wild-type fungus). The data obtained indicate
      that wc-1 and wc-2 genes of N. crassa are involved in light-dependent formation
      of protoperithecia and conidia. The effects of 5-azacytidine (an inhibitor of DNA
      methylation) under the same experimental conditions suggest that the balance
      between the formation of sexual and asexual reproductive structures, maintained
      in N. crassa, depends on genome methylation processes sensitive to the action of
      light, which is mediated by the photoreceptor complex of WC proteins.

PMID- 15455722
TI  - [Comamonas testosteroni strain TI as a potential base for a microbial sensor
      detecting surfactants].
AB  - Strain Comamonas testosteroni TI, capable of degrading the nonionic surfactant
      (NIS) nonylphenolethoxylate (OP-10), was used for constructing a pilot cellular
      biosensor. The lower NIS detection limit for the biosensor was 0.25 mg/l. We
      studied the substrate specificity of the biosensor with respect to a wide range
      of organic compounds: surfactants, polyaromatic compounds (PAC), carbohydrates,
      alcohols, etc. It was shown that the biosensor based on Comamonas testosteroni TI
      did not respond to glucose, which was an advantage over the formerly described
      biosensor based on Pseudomonas rathonis T. The amplitude of the sensor response
      remained stable for 10 days.

PMID- 15455723
TI  - [Determination of tetanus toxin and toxoid by ELISA using monoclonal antibodies].
AB  - The procedure of obtaining monoclonal antibodies TT-1, TT-2, and TT-3 against
      tetanus toxin/toxoid is described. It is shown that both commercial DTP vaccine
      and tetanus toxoid conjugated with a low-molecular-weight hapten can be used an
      immunogens. Monoclonal antibodies TT-1 and TT-2 neutralized tetanus toxin in
      vivo. The monoclonal antibodies obtained were used to design and compare several
      schemes of quantitative determination of tetanus toxoid and toxin by ELISA. A
      more sensitive competitive ELISA allowed detecting as much as 0.01 EC/ml toxoid
      and 50 LD50/ml toxin.

PMID- 15455724
TI  - [Interaction of perch fucolectin with Lewis antigens].
AB  - Interaction of fucolectin of perch Perca fluviatilis (PFL) with a set of Lewis
      antigens was studied by monitoring changes in its tryptophan fluorescence. PFL
      bound Le(c) (H type 1)-pentasaccharide (Ka = 6.6 x 10(3) M(-1)) and H type 6
      trisaccharide (Ka = 2.5 x 10(3) M(-1)); essentially weaker, with Le(b)
      hexasaccharide (Ka = = 4.0 x 10(2) M(-1)); and failed to interact with Le(a)-,
      Le(x)-, and Le(d)-containing oligosaccharides. PFL belongs to a new type of the
      fucolectins recognizing H-disaccharide Fuc alpha1-2Gal within various antigens,
      including H type 1/2 and Le(b).

PMID- 15455725
TI  - [Effect of ambiol on the ultrastructure of mitochondria in the apical cells of
      tubers of original and transgenic potato plants].
AB  - The ultrastructure of the mitochondrial apparatus of apical tuber cells of
      original and transgenic (defensin gene-transfected) potato have been compared in
      normal and ambiol-treated plants, using morphometric approaches. No qualitative
      or quantitative differences were found between the mitochondria of original and
      transgenic plants under normal conditions (control). Treatment with ambiol
      produced only quantitative differences (in the number of mitochondria and their
      volume) between the cells of original and transgenic plants. This observation has
      been attributed to (1) changes in the physiology and biochemistry of transgenic
      plants, induced by the expression of the gene of defensin (hormonal balance,
      functional activity of the plasmalemmata, etc.), and (2) direct effects of
      ambiol.

PMID- 15455726
TI  - Morphological study of the Golgi tendon organ in equine superficial digital
      flexor tendon.
AB  - The Golgi tendon organ (GTO) is an encapsulated fusiform mechanoreceptor siding
      in the musculo-tendinous junction of many animal species. Inhibitory function of
      afferent nerve fibers distributed from nearby motor units, the organ responds to
      active tension exerted onto the muscle. The morphological features of the equine
      GTO have not yet been elucidated. Additionally, there is some controversy
      regarding to the existence of the GTO in the equine superficial digital flexor
      tendon (SDFT). Therefore, immunohistochemistry and immunoelectron microscopy
      using alcian blue (pH 2.5) staining and the silver-enhanced colloidal gold method
      were carried out to determine both the location and characteristics of the GTO at
      the musculo-tendinous junction of the SDFT. A GTO with a fusiform structure of
      approximately 3 mm in length was found in the tendinous part. The lumen of the
      GTO was divided into compartments by septal cells. Each compartment contained
      collagen fibrils, nerve fibers and Schwann cells. This is the first report of the
      equine GTO.

PMID- 15455727
TI  - Morphology of the lingual papillae in the tiger.
AB  - The dorsal lingual surfaces of an adult tiger (Panthera tigris altaica) was
      examined by macroscopical and scanning electron microscopical observations.
      Filiform, fungiform and vallate papillae were observed. The filiform papillae
      were distributed over the entire dosal surface of the tongue. The fungiform
      papillae were present rounded bodies, and more densely distributed on the lingual
      apex. There were 4 vallate papillae in total on borderline between the lingual
      body and lingual radix. Each papilla was surrounded by a groove. No foliate
      papillae were seen on the dorsal surface. Openings of the glandular ducts on the
      regions of the vallate papillae were found.

PMID- 15455728
TI  - Branch of mylohyoid and lingual nerves on submandibular and submental triangles.
AB  - The mylohyoid nerve (MN) displays several branches in the posterior,
      intermediate, and anterior region of the mylohyoid muscle (MM) as it courses on
      the internal surface of the mandibular body. Branches in the intermediate region
      were found in 66% of the cases (272 out of 413 sides). In the submandibular
      triangle, one or two large branches of the MN communicated with the lingual nerve
      at submandibular triangle and submental triangle in 1.45% of the cases (6 out of
      413 sides). These distributions of nerve supply are an important in the
      operations of radical neck dissection on the submandibular triangle.

PMID- 15455729
TI  - Distribution of tenascin-C and -X, and soft X-ray analysis of the mandibular
      symphysis during mandible formation in the human fetus.
AB  - In the development of the human mandible, the process of bone calcification,
      distribution and expression of tenascin-C and -X in the mental symphyseal region
      are unknown. The purpose of this study was to determine the distribution of these
      extracellular matrices in the connective tissue around calcified tissues located
      on the mental symphyseal region of the human fetus during development through
      histological and radiographical studies. The radiographic density increased from
      16 weeks to 24 weeks gestation in all examined regions; in contrast, the diameter
      of muscle fiber in the suprahyoid muscles (digastric anterior and geniohyoid
      muscles) inserted into the inner mental symphyseal region increased from 24 weeks
      gestation. The extracellular matrices (tenascin) were shown to have a different
      distribution in the mental symphyseal region of the human fetus at each stage.
      These different distributions of tenascin-C and -X were found around the
      epithelium and the endomysium of the mental symphyseal region, and affect the
      specific formation of the mandible during ossification with hyoid muscle
      development in human fetus.

PMID- 15455730
TI  - Periodontal diseases and the risk of coronary heart and cerebrovascular diseases:
      a meta-analysis.
AB  - BACKGROUND: This meta-analysis was conducted to examine the relationship between
      periodontal diseases and coronary heart diseases (CHD) and cerebrovascular
      diseases (CVD) in observational studies. METHODS: This study was based on seven
      cohort studies and four studies of other designs that met prestated inclusion
      criteria. Information on study design, year of publication, study location,
      sample size, study population, participant characteristics, measurement of risk
      factors, exposure and outcome measures, matching, controlling for confounders,
      and risk estimates was abstracted independently by two investigators using a
      standard protocol. RESULTS: Subjects with periodontitis had an overall adjusted
      risk of CHD that was 1.15 times (95% confidence interval [CI]: 1.06 to 1.25; P =
      0.001) the risk for healthy subjects. There was no heterogeneity among the
      studies in the overall relative risk estimate (P = 0.472). As compared to healthy
      subjects, those with periodontitis had an overall adjusted relative risk of CVD
      of 1.13 (95% CI: 1.01 to 1.27; P = 0.032). CONCLUSIONS: Findings indicated that
      periodontal infection increases the risk of CHD and CVD. However, this meta
      analysis provided no evidence for the existence of strong associations between
      periodontitis and CHD and CVD. Larger and better-controlled studies involving
      socially homogeneous populations and measuring specific periodontal pathogens are
      required to identify a definite association between periodontal disease and the
      risk of coronary heart disease and cerebrovascular disease.

PMID- 15455731
TI  - Effect of tranilast on matrix metalloproteinase-1 secretion from human gingival
      fibroblasts in vitro.
AB  - BACKGROUND: Some drugs such as phenytoin, calcium blockers, or cyclosporins are
      known to cause gingival fibrous hyperplasia, an unwanted side effect. Decreased
      collagen catabolism in overgrown gingival tissue has been proposed as one of the
      reasons causing the disease. The effect of tranilast, which suppresses collagen
      synthesis and cell proliferation, on matrix metalloproteinase (MMP-1) secretion
      from human gingival fibroblast, was studied in vitro. METHODS: Human gingival
      fibroblasts were cultured from specimens taken from healthy, periodontal, and
      overgrown gingival tissues. The effects of tranilast on cell proliferation and
      MMP-1 secretion from gingival fibroblast were assessed. Inhibitory effect of
      transforming growth factor (TGF)-beta secretion from gingival fibroblast by
      tranilast was also evaluated. RESULTS: Tranilast did not interfere with cell
      proliferation at the low concentrations. MMP-1 concentration significantly
      increased at the lower doses of tranilast up to about 2-fold compared to controls
      (P < 0.05). In contrast, higher doses of tranilast significantly decreased
      activity to 30% and 20%, respectively. MMP-1 secretion was inhibited
      significantly by phenytoin, nifedipine, and cyclosporin A and the depressed MMP-1
      recovered to the control level with tranilast. The amount of secretion from
      normal and periodontitis gingival fibroblast specimens did not differ, but that
      from the overgrown gingiva was significantly less than the other types. Moreover,
      TGF-beta secretion was significantly inhibited by 300 microM of tranilast.
      CONCLUSIONS: Tranilast upregulates the expression of type 1 collagenase
      suppressed by gingival overgrowth-inducing drugs, and inhibits TGF-beta secretion
      from gingival fibroblasts. Therefore, tranilast could be considered as an agent
      for controlling gingival over-growth.

PMID- 15455732
TI  - Morphometric analysis of implant-related anatomy in Caucasian skulls.
AB  - BACKGROUND: Sequelae related to implant placement/advanced bone grafting
      procedures are a result of injury to surrounding anatomic structures. Damage may
      not necessarily lead to implant failure; however, it is the most common cause of
      legal action against the practitioner. This study aimed to describe morphological
      aspects and variations of the anatomy directly related to implant treatment.
      METHODS: Morphometric analyses were performed in 22 Caucasian skulls.
      Measurements of the mental foramen (MF) included height (MF-H), width (MF-W), and
      location in relation to other known anatomical landmarks. Presence or absence of
      anterior loops (AL) of the inferior alveolar nerve (IAN) was determined, and the
      mesial extent of the loop was measured. Additional measurements included height
      (G-H), width (G-W), thickness (G-T), and volume (G-V) of monocortical onlay
      grafts harvested from the mandibular symphysis area, and thickness of the lateral
      wall (T-LW) of the maxillary sinus. The independent samples t test, and a two
      tailed t test with equal variance were utilized to determine statistical
      significance to a level of P < 0.05. Multiple regression analyses were performed
      to determine if each one of these measurements was affected by age and gender.
      RESULTS: The most common location of the MF in relation to teeth was found to be
      below the apices of mandibular premolars. The mean MF-H was 3.47 +/- 0.71 mm and
      the mean MF-W was 3.59 +/- 0.8 mm. The mean distance from the MF to other
      anatomical landmarks were: MF-CEJ = 15.52 +/- 2.37 mm, MF to the most apical
      portion of the lower cortex of the mandible = 12.0 +/- 1.67 mm, MF to the midline
      = 27.61+/- 2.29 mm, and MF-MF = 55.23 +/- 5.34 mm. A high prevalence of AL was
      found (88%); symmetric occurrence was a common finding (76.2%), with a mean
      length of 4.13 +/- 2.04 mm. The mean size of symphyseal grafts was: G-H = 9.45 +/
      1.08 mm, G-W = 14.5 +/- 3.0 mm, and G-T = 6.15 +/- 1.04 mm, with an average G-V
      of 857.55 +/- 283.97 mm3 (range: 352 to 1,200 mm3). The mean T-LW of the
      maxillary sinus was 0.91 +/- 0.43 mm. CONCLUSION: Implant-related anatomy must be
      carefully evaluated before treatment due to considerable variations among
      individuals, in order to prevent injury to surrounding anatomical structures and
      possible damage.

PMID- 15455733
TI  - Subantimicrobial dose doxycycline enhances the efficacy of scaling and root
      planing in chronic periodontitis: a multicenter trial.
AB  - BACKGROUND: Previous studies have shown that subantimicrobial dose doxycycline
      (SDD) is of clinical benefit in the treatment of chronic periodontitis (CP). The
      aim of this study was to further assess the role of SDD as an adjunct to scaling
      and root planing (SRP) in the treatment of CP. METHODS: A double-blind,
      randomized, placebo-controlled, multicenter clinical study was conducted to test
      the efficacy of SDD (20 mg doxycycline B.I.D.) in combination with SRP in
      subjects with moderate to severe CP. Two-hundred ten subjects were treated with a
      standardized episode of SRP and randomized to receive either adjunctive SDD or
      placebo for 9 months. Efficacy parameters included per-subject mean changes in
      clinical attachment level (CAL) and probing depth (PD) from baseline, and the
      total number of sites with attachment gains and probing depth reductions > or = 2
      mm and > or = 3 mm from baseline. RESULTS: In periodontal sites with PD 4 to 6 mm
      and > or = 7 mm (N = 209, intent-to-treat population), mean improvements in CAL
      and PD were greater following SRP with adjunctive SDD than SRP with placebo,
      achieving statistical significance in all baseline disease categories at month 9
      (P < 0.05). At month 9, 42.3% of sites in the SDD group demonstrated CAL gain >
      or = 2 mm compared to 32.0% of sites in the placebo group (P < 0.01). CAL gain >
      or = 3 mm was seen in 15.4% of sites in the SDD group compared to 10.6% of sites
      in the placebo group (P < 0.05). When considering the same thresholds of change
      in PD, 42.9% of sites in the SDD group compared to 31.1% of sites in the placebo
      group demonstrated PD reduction > or = 2 mm (P < 0.01), and 15.4% of sites in the
      SDD group compared to 9.1% of sites in the placebo group demonstrated PD
      reduction > or = 3 mm (P < 0.01). CONCLUSION: Adjunctive subantimicrobial dose
      doxycycline enhances scaling and root planing. It results in statistically
      significant attachment gains and probing depth reductions over and above those
      achieved by scaling and root planing with placebo.

PMID- 15455734
TI  - Occurrence of Porphyromonas gingivalis and Tannerella forsythensis in
      periodontally diseased and healthy subjects.
AB  - BACKGROUND: The purpose of this study was to compare the prevalence and level of
      Porphyromonas gingivalis (P. gingivalis) and Tannerella forsythensis (T.
      forsythensis) in subgingival plaque samples from both healthy individuals and
      periodontal patients in different age groups. METHODS: A total of 498 subgingival
      plaque samples were studied. These samples were collected from 407 individuals
      diagnosed with periodontal disease (210 adult periodontitis [AP], 78 rapidly
      progressive periodontitis [RPP], and 119 refractory periodontitis [Ref-P] cases)
      and 91 healthy (H) subjects. P. gingivalis and T. forsythensis were detected by
      indirect immunofluorescent assay using species-specific polyclonal antisera to P.
      gingivalis strain (FDC 381) and T. forsythensis strain (FDC 335). The prevalence
      of P. gingivalis and T. forsythensis was compared by chi-square analysis.
      Differences in P. gingivalis and T. forsythensis levels among various periodontal
      status and age groups was determined by one-way analysis of variance and Fisher's
      multiple comparison tests. The association between the presence of P. gingivalis
      or T. forsythensis in different periodontal status and age groups was measured
      using odds ratios. RESULTS: P. gingivalis was found in 85.7% (P < 0.0001) and T.
      forsythensis in 60.7% (P = 0.0002) of diseased subjects compared to 23.1% and
      39.6%, respectively, in healthy subjects. P. gingivalis, but not T. forsythensis,
      was detected more frequently in any diseased group than in the H group in every
      age group (P<0.0001). No significant difference was found in the prevalence of P.
      gingivalis and T. forsythensis among age groups, except T. forsythensis was more
      prevalent in the age group of 40 to 59 years than in the age group < 20 years
      (chi2 = 3.93, P = 0.047) in the H group. The mean level of P. gingivalis and T.
      forsythensis was significantly higher in diseased groups than in the H group (P <
      0.0001). The odds ratio for P. gingivalis in the AP group (25.0) was greater than
      any other group for P. gingivalis or T. forsythensis compared to the H group.
      CONCLUSIONS: These data suggested that P. gingivalis is closely associated with
      the pathogenesis of periodontitis and that it may not be a normal inhabitant of
      periodontally healthy subjects. T. forsythensis is also important in the
      pathogenesis of periodontal disease; however, whether it causes periodontal
      disease or is a secondary invader of periodontal lesions remains to be
      determined.

PMID- 15455735
TI  - Possible periodontal pathogens associated with clinical symptoms of periodontal
      disease in Japanese high school students.
AB  - BACKGROUND: The purpose of this study is to investigate how the components of
      biofilm and clinical oral status change in adolescents and to identify specific
      periodontal pathogens as risk markers for the onset of periodontitis. METHODS:
      One hundred seven high school students (72 boys and 35 girls, all 15 years old)
      were recruited. The mesio-lingual site of the left lower first molar was selected
      as the examined site. Probing depth (PD), bleeding on probing (BOP), the presence
      of subgingival calculus, and Community Periodontal Index (CPI) were determined by
      examination with a WHO probe. The prevalence and proportion of seven selected
      periodontal pathogens (Porphyromonas gingivalis, Tannerella forsythensis,
      Prevotella intermedia, Campylobacter rectus, Eikenella corrodens, and
      Actinobacillus actinomycetemcomitans serotypes b and c) were determined by
      indirect immunofluorescent technique, and the prevalence and proportion of
      spirochetes were determined by their morphology under dark-field microscopy. The
      relationship between the periodontal status and the bacterial condition was
      statistically analyzed. RESULTS: The mean proportion of T. forsythensis was
      significantly higher in BOP (+) sites compared with BOP (-) sites (3.47% +/-
      5.35% versus 0.83% +/- 1.95%) and in CPI 3 sites compared with CPI 0 sites (3.29%
      +/- 5.28% versus 0.68% +/- 1.37%). The mean proportion of C. rectus was
      significantly increased in BOP (+) compared with BOP (-) (2.01% +/- 2.48% versus
      0.79% +/- 0.91%) and in CPI 3 sites compared with CPI 0 sites (2.04% +/- 2.64%
      versus 0.80% +/- 0.79%). CONCLUSION: The results indicated that T. forsythensis
      and C. rectus might be able to be used as risk markers for the onset of
      periodontitis.

PMID- 15455736
TI  - Polymorphisms in the vitamin D receptor gene are associated with periodontal
      disease.
AB  - BACKGROUND: Genetic polymorphisms in the vitamin D receptor (VDR) gene are
      associated with bone homeostasis and diseases in which bone loss is a cardinal
      sign. The aim of this study was to determine whether chronic periodontal disease
      in a Brazilian population is associated with polymorphisms in the VDR gene.
      METHODS: Clinical examination and recordings of probing depth and clinical
      attachment level were performed in 113 unrelated adults who were divided into two
      groups: 44 healthy individuals (control group) and 69 subjects with chronic
      periodontitis (CP). DNA was obtained from the subjects' epithelial cells by
      scraping the buccal mucosa. Two polymorphisms in the VDR gene were analyzed by
      polymerase chain reaction, followed by Taql and BsmI restriction endonuclease
      digestion. RESULTS: Frequencies of VDR/TaqI and VDR/BsmI showed significant
      differences between the control group and the CP group (P < 0.05). The "Tb"
      haplotype was prevalent in the control group (43.2%), and the "TB" haplotype in
      the CP group (36.6%). The "TB" haplotype seemed to increase susceptibility to
      periodontal disease (odds ratio [OR] = 2.19). The heterozygous haplotype "TB/tb"
      was predominant in the CP group (OR = 4.32; P = 0.005). CONCLUSIONS: TaqI and
      BsmI polymorphisms of the VDR gene are associated with clinical attachment loss
      due to periodontal disease in a Brazilian population. These findings suggest that
      VDR genotype might be a risk indicator for susceptibility to chronic
      periodontitis.

PMID- 15455737
TI  - Tetracycline impregnation delays collagen membrane degradation in vivo.
AB  - BACKGROUND: Guided tissue and bone regeneration using bioabsorbable collagen
      membranes is a common practice. Collagen promotes progenitor cell adhesion,
      chemotaxis, homeostasis, and physiologic degradation with low immunogenicity,
      which makes it an ideal material for barrier preparation. Collagen membranes have
      to maintain integrity for a proper time, thus ensuring successful cell exclusion.
      Early collagen membrane degradation is detrimental for the success of
      regenerative procedures. This in vivo study was conducted to evaluate the effect
      of soaking collagen membranes in different tetracycline hydrochloride (TCN)
      concentration solutions on its degradation. METHODS: Five mm disks of collagen
      membrane were soaked in either 100 mg/ml TCN (group 100) or 50 mg/ml TCN (group
      50); a group of non-treated disks served as controls. All disks were labeled with
      aminohexanoyl-biotin-N-hydroxy-succinimide ester (biotin) and implanted in rat
      calvaria bone. Block sections were taken after 3 weeks and histological slides
      stained with horseradish peroxidase (HRP) to detect remnants of biotinylated
      collagen. Staining intensity was analyzed by image-analysis software taking
      quadruplicate measurements of a 500 microm2 area each. Data were analyzed using
      analysis of variance (ANOVA) with repeated measures and paired t test with
      Bonferroni correction. RESULTS: Staining intensity of membranes in group 100 was
      > 5-fold higher than the control while group 50 exhibited > 11-fold higher
      intensity than the control and > 2.5-fold higher than the 100. All of these
      differences were statistically significant (P < 0.001). CONCLUSION: Soaking
      collagen membranes in 50 mg/ml TCN solution is a useful, practical, and simple
      tool to slow membrane degradation.

PMID- 15455738
TI  - The interface between retained roots and dental implants: a histologic study in
      baboons.
AB  - BACKGROUND: This study is a derivative of another study evaluating implant
      efficacy in baboons. In the previous study it was noted that some implants were
      placed near or into retained root tips. The purpose of this study was to evaluate
      the effect of the inadvertent placement of root form implants into or near
      retained root fragments. METHODS: The baboon has severe dilacerations at the
      apices of the roots, making extraction very difficult; 120 teeth were extracted
      from 10 baboons. After the sites had healed, root form implants were placed in
      each of the sites. Sites were either loaded at various time intervals or left
      unloaded. Block sections were removed and processed for histologic examination.
      RESULTS: When the specimens were analyzed, it was noted that several implants
      were placed through retained root fragments, while others were placed through the
      periodontal ligament of other root fragments. In a few cases, implants were close
      to, but not in contact with, either the root or the periodontal ligament. These
      implants functioned as well as the others in the study. Histologically, there was
      no inflammation at any site. In some sections, the roots were in intimate contact
      with the implants, while in others, there was a gap between the two. Where the
      implant was in contact with the periodontal ligament, there was no apparent
      fibrous encapsulization of the implant. In some areas, it appeared that a
      calcified material was deposited on the implants. It was not possible to
      determine whether this material was bone or cementum. CONCLUSION: Unintentional
      placement of dental implants into retained root fragments did not result in any
      inflammation and may have produced cementum or cementum-like matrix on the
      titanium surface adjacent to the periodontal ligament of the retained root tip.

PMID- 15455739
TI  - One- and 3-minute plaque removal by a battery-powered versus a manual toothbrush.
AB  - BACKGROUND: A new battery-powered toothbrush with a fundamentally different
      design than other powered toothbrushes has recently been introduced. The new
      toothbrush has a powered oscillating round head and a second powered head that
      translates back and forth. This study compared the plaque removal efficacy of a
      manual toothbrush to this new powered toothbrush. METHODS: This randomized,
      controlled, examiner-masked, four-period cross-over study examined plaque removal
      with the two toothbrushes following a single use in 40 subjects. Plaque was
      scored before brushing and after 1 and 3 minutes of brushing using the Turesky
      modification of the Quigley-Hein index. RESULTS: Baseline plaque scores were 2.98
      prior to using the powered toothbrush and 2.99 prior to using the manual
      toothbrush. The powered toothbrush delivered a covariance-adjusted mean plaque
      score change from baseline of 0.61 after 1 minute of brushing and 0.93 after 3
      minutes of brushing. The adjusted mean changes for the manual toothbrush were
      0.43 and 0.62, respectively. The differences between treatment groups were
      statistically significant (P < 0.001) after both 1 and 3 minutes of brushing. The
      powered toothbrush had, on average, 42.1% and 49.6% greater plaque removal scores
      after 1 minute and 3 minutes of brushing, respectively. Both toothbrushes had
      statistically significantly greater plaque removal scores after 3 minutes than
      after 1 minute of brushing (P < 0.001). Plaque removal scores for each toothbrush
      after 3 minutes of brushing were about 50% higher than the scores after 1 minute
      of brushing. CONCLUSIONS: The powered toothbrush delivered statistically
      significantly superior plaque removal after both 1 and 3 minutes of brushing
      compared to the manual toothbrush. Both toothbrushes showed statistically
      significantly greater plaque removal following 3 minutes of brushing than
      following 1 minute of brushing, and the difference between the toothbrushes was
      greater following 3 minutes of brushing than following 1 minute of brushing.

PMID- 15455740
TI  - Clinical and microbiological effects of topical subgingival application of
      hyaluronic acid gel adjunctive to scaling and root planing in the treatment of
      chronic periodontitis.
AB  - BACKGROUND: Hyaluronic acid (HA) has shown anti-inflammatory effects in
      gingivitis therapy. The potential benefits of local subgingival application of HA
      adjunctive to scaling and root planing (SRP) were evaluated in this study.
      METHODS: Twenty patients with chronic periodontitis were included in this split
      mouth study. Sulcus fluid flow rate (SFFR) and sulcus bleeding index were
      monitored at baseline and after 1, 2, 3, 4, 5, 6, and 12 weeks; probing depth and
      clinical attachment level were monitored at baseline and 6 and 12 weeks.
      Subgingival plaque samples were also taken at these same three appointments to
      determine the presence of Actinobacillus actinomycetemcomitans, Porphyromonas
      gingivalis, Prevotella intermedia, Tannerella forsythensis, and Treponema
      denticola. All patients were treated with full-mouth scaling and root planing
      (SRP); in addition, an HA gel was administered subgingivally in the test sites
      every week for 6 weeks. RESULTS: An improvement of all clinical variables was
      observed (P < 0.05) in both groups. Clinically, no difference between test and
      control sites could be found. No difference between test and control sites was
      seen in the tested microorganisms. CONCLUSIONS: No clinical or microbiological
      improvement was achieved by the adjunctive use of HA gel compared to SRP alone.
      Only SFFR was affected by the use of HA in terms of a more rapid reduction of
      SFFR in the test sites.

PMID- 15455741
TI  - Localization of the NO-cGMP signaling pathway molecules, NOS III-phosphorylation
      sites, ERK1/2, and Akt/PKB in osteoclasts.
AB  - BACKGROUND: Nitric oxide (NO) mediates different cellular functions by activating
      soluble guanylate cyclase (sGC) that converts guanosine-5'-triphosphate (GTP) to
      cyclic guanosine-3',5'-monophosphate (cGMP). Membrane-bound GCs produce cGMP in
      response to natriuretic peptides in osteoblasts, but neither the NO-target enzyme
      sGC, nor the phosphorylation sites of NOS III, nor their regulation by
      extracellular signal-regulated kinases 1 and 2 (ERK1/2) and Akt/protein kinase B
      (Akt/PKB) in osteoclasts have been established. METHODS: Rat molars with
      periodontium were perfusion- and post-fixed, decalcified, and frozen-sectioned.
      Free-floating sections were stained using nicotinamide adenine dinucleotide
      phosphate-diaphorase (NADPH-d) and tartrate-resistant acid phosphatase (TRAP)
      histochemical techniques and immunoreacted with antisera against NO-synthase
      (NOS) I-III, NOS III phoshorylated at Thr495, NOS III phoshorylated at Serine1177
      (Ser1177), ERK1/2, phosphorylated ERK1/2, Akt/PKB, phosphorylated Akt/PKB, sGC
      (alpha2/beta1), and cGMP. RESULTS: NADPH-d staining and immunostaining of NOS I
      III, NOS III phosphorylated at Ser1177, ERK1/2, Akt/PKB, phosphorylated Akt/PKB,
      sGC (alpha2 and beta1-subunits), and cGMP were detected in osteoclasts.
      Immunohistochemical reaction products for NOS III phosphorylated at threonine495
      (Thr495) and phosphorylated ERK1/2 could not be identified in osteoclasts.
      Comparison of TRAP activity and immunostaining for sGC beta1-subunit revealed
      that sGC beta1-subunit is only expressed in a sub-population of osteoclasts.
      CONCLUSIONS: NO is likely to be generated by NOS I and NOS III in osteoclasts.
      The inconstant expression of NOS II in some osteoclasts may be explained with
      inducible expression of NOS II upon physiological cell activation. Localization
      of the sGC alpha2- and beta1-subunits and cGMP in osteoclasts is compatible with
      an involvement of NO-sGC signaling in the homeostasis of osteoclasts. The
      phosphorylation site of NOS III at Ser1177 and phosphorylated Akt/PKB are
      involved in regulation of NO production by NOS III in osteoclasts under basal
      conditions.

PMID- 15455742
TI  - Leucine-rich amelogenin peptide: a candidate signaling molecule during
      cementogenesis.
AB  - BACKGROUND: Cementum is a critical mineralized tissue; however, control of its
      formation remains undefined. One hypothesis is that enamel matrix
      proteins/peptides secreted by ameloblasts and/or epithelial rest cells contribute
      to the control of cementum formation via epithelial-mesenchymal interactions.
      Here, we focused on determining whether or not leucine-rich amelogenin peptide
      (LRAP), translated from an alternatively spliced amelogenin RNA, altered
      cementoblast behavior. METHODS: Immortalized murine cementoblasts (OCCM-30) were
      exposed to LRAP and evaluated for: 1) proliferative activity; 2) gene expression
      using Northern blot for Cbfal (core binding factor alpha-1); OCN (osteocalcin),
      OPN (osteopontin), and real-time reverse transcription-polymerase chain reaction
      (RT-PCR) for OPG (osteoprotegerin); and RANKL (receptor activator of NF-kappaB
      ligand); 3) signaling pathway using inhibitors of PKA (THFA), PKC (GF109203X),
      and MAPK (UO126); and 4) mineralization evaluated by von Kossa and Alizarin-red.
      RESULTS: LRAP had no effect on cell proliferation up to 6 days, with a decrease
      in cell growth observed at the highest dose by 9 days versus untreated cells.
      LRAP down regulated OCN and up regulated OPN in a dose- and time-response
      fashion, and inhibited the capacity of mineral nodule formation. Transcripts for
      OPG were increased in LRAP-treated cells compared to control, but RANKL mRNA
      levels were not affected. Core binding factor alpha (Cbfa) mRNA, expressed
      constitutively, was not affected by LRAP. Signaling pathway assays suggested
      involvement of the MAPK pathway, since the addition of the MAPK inhibitor
      suppressed OPN expression in LRAP-treated cells. CONCLUSION: Leucine-rich
      amelogenin peptide appears to have a direct effect on cementoblast activity that
      may prove significant during development as well as in regeneration of
      periodontal tissues.

PMID- 15455743
TI  - Coronally positioned flap with or without acellular dermal matrix graft in the
      treatment of Class I gingival recessions: a randomized controlled clinical study.
AB  - BACKGROUND: The aim of this study was to clinically evaluate the treatment of
      Class I gingival recessions by coronally positioned flap with or without
      acellular dermal matrix allograft (ADM). METHODS: Thirteen patients with
      comparable bilateral Miller Class I gingival recessions (> or = 3.0 mm) were
      selected. The defects were randomly assigned to one of the treatments: coronally
      positioned flap and acellular dermal matrix (ADM group) or coronally positioned
      flap alone (CPF group). The clinical parameters included: probing depth (PD),
      clinical attachment level (CAL), recession height (RH), recession width (RW),
      height of keratinized tissue (HKT), thickness of keratinized tissue (TKT), plaque
      index (PI), and gingival index (GI). The measurements were taken before the
      surgeries and after 6 months. RESULTS: The mean baseline recession was 3.4 mm and
      3.5 mm for ADM group and CPF group, respectively. After 6 months, both treatments
      resulted in significant root coverage (P < 0.01), reaching an average of 2.6 mm
      (76%) in the ADM group and 2.5 mm (71%) in the CPF group. The difference in
      recession reduction between treatments was not statistically significant. There
      were no statistically significant differences between the treatments in PD, CAL,
      RH, RW, and HKT. However, the mean TKT gain was 0.7 mm for the ADM group and 0.2
      mm for the CPF group (P < 0.01). CONCLUSION: It can be concluded that both
      techniques could provide significant root coverage in Class I gingival
      recessions; however, a greater keratinized tissue thickness can be expected with
      ADM.

PMID- 15455744
TI  - Comparison between subtraction radiography and conventional radiographic
      interpretation during long-term evaluation of periodontal therapy in Class II
      furcation defects.
AB  - BACKGROUND: Limited information comparing digital subtraction radiographic
      assessment with conventional radiographic interpretation is available from
      longitudinal clinical trials. The aim of this study was to evaluate the ability
      to detect periodontal bone changes during the long-term maintenance of Class II
      furcation defects by conventional radiographic interpretation compared to
      interpretation of digital subtraction images. METHODS: Standardized radiographs
      of 18 Class II furcation defects in mandibular molars were taken at baseline and
      at 6, 12, 18, and 24 months after non-resective periodontal surgery. Conventional
      radiographic and digital subtraction interpretations were performed masked,
      respectively, by two and three experienced examiners, according to the following
      categories: bone gain; bone loss; unchanged appearance; and impossible to
      visualize. Percent concordance and the kappa statistic value (kappa) were
      computed. RESULTS: Conventional radiographic and digital subtraction
      interpretation images resulted in 72 decisions for each examiner. The visual
      interpretation of digital subtraction images by two examiners revealed the same
      results. The interpretation of conventional radiographic images showed a low
      concordance between examiners (kappa < 0.40) at all examinations. The concordance
      between subtraction radiography and conventional radiographic interpretation was
      also low for all examiners (kappa < 0.36) at all examinations. Using subtraction
      radiography as a reference, bone changed and bone unchanged were diagnosed
      correctly in 47.2% of cases by examiner A, in 43.1% by examiner B, and in 38.9%
      by examiner C. CONCLUSION: It can be concluded that conventional radiographic
      interpretation is a more subjective and inaccurate method of detecting
      periodontal bone changes in Class II furcation defects in mandibular molars when
      compared with subtraction radiography.

PMID- 15455745
TI  - A randomized clinical trial comparing enamel matrix derivative and membrane
      treatment of buccal Class II furcation involvement in mandibular molars. Part I:
      Study design and results for primary outcomes.
AB  - BACKGROUND: The objective of this multicenter, randomized trial was to compare
      enamel matrix derivative (EMD; test) with barrier membranes (control) for the
      treatment of mandibular buccal Class II furcation defects. METHODS: Forty-five
      patients with 90 comparable defects on contralateral molars were included.
      Defects were randomly assigned to EMD or bioabsorbable barrier membrane; the
      contralateral defect received the alternative treatment. Assessments at baseline
      and 8 and 14 months included gingival margin levels, probing depths, bleeding on
      probing, vertical attachment levels, and vertical bone sounding from a stent at
      five buccal sites/ tooth. Defect dimensions were recorded at surgery and during
      reentry at 14 months. Change of open horizontal furcation depth was the primary
      outcome variable. Adverse reactions and patient perceptions were also noted.
      RESULTS: Both treatment modalities led to significant clinical improvements. The
      median reduction of open horizontal furcation depth was 2.8 mm with the
      corresponding interquartile interval (1.5 mm, 3.5 mm) at test sites compared with
      1.8 mm (1.0 mm, 2.8 mm) at control sites. The Hodges-Lehmann estimator of the
      advantage (reduction test versus control) was 0.75 mm (95% confidence interval
      [CI]: 0.125 mm, 1.375 mm, P = 0.033, Wilcoxon). The frequency of complete
      furcation closure was 8/45 (test) and 3/45 (control); partial closure, 27/45 in
      both groups; no change, 9/45 and 11/45, respectively; and deterioration, 1/45 and
      4/45, respectively. The frequency of no pain or no swelling at 1 week post
      surgery was 62% and 44%, respectively, at the test sites and 12% and 6% at the
      control sites. CONCLUSION: There was a significantly greater reduction in
      horizontal furcation depth and a comparatively lower incidence of postoperative
      pain/swelling following enamel matrix derivative compared to membrane therapy.

PMID- 15455746
TI  - Osseointegration in a sinus augmented with bovine porous bone mineral:
      histological results in an implant retrieved 4 years after insertion. A case
      report.
AB  - BACKGROUND: A subject of controversy in implant dentistry is what is the most
      appropriate material for sinus augmentation. Little is known about the healing
      pattern and the osseointegration processes at the interface of implants placed in
      different grafting materials in man. Bovine porous bone mineral (BPBM) is a
      xenogenic material similar to human cancellous bone with a high biocompatibility
      and osteoconductivity. METHODS: A 50-year-old patient presented a posterior left
      maxilla with an insufficient bone height for implant insertion. In January 1999,
      a sinus lifting procedure was performed and the left sinus was augmented with
      BPBM; in November 1999, three implants were inserted, and in July 2000 a fixed
      prosthetic restoration was positioned. In June 2003 the connecting screw of the
      middle implant fractured and it was decided to remove the implant using a 5 mm
      trephine bur. RESULTS: All BPBM particles were surrounded by newly formed bone.
      No BPBM particle was in direct contact with the implant surface, and between the
      implant surface and the particles there was newly-formed bone. BPBM seemed to
      undergo a very slow resorption; the particles constituted 36% +/- 3% of the peri
      implant tissues. The bone-implant contact percentage was 72% +/- 4%. CONCLUSIONS:
      In our specimens, we found an intimate, direct contact between bone and implant
      without an interposition of the graft material particles. A very high bone-to
      implant contact percentage was present. Our results show that the slow resorption
      of the graft particles did not jeopardize the osseointegration of the implant.

PMID- 15455747
TI  - Expanded mesh connective tissue graft for the treatment of multiple gingival
      recessions.
AB  - BACKGROUND: The connective tissue graft procedure is an effective method to
      achieve root coverage. Although multiple sites often need grafting, the palatal
      mucosa supplies only a limited area of grafting material. The expanded mesh graft
      provides a method whereby a graft can be stretched to cover a larger area. The
      aim of this study was to determine the effectiveness and the predictability of
      expanded mesh connective tissue graft (e-MCTG) in the treatment of multiple
      gingival recessions. METHODS: Fifty-two buccal gingival recessions were treated
      in 10 systemically healthy patients. Fifteen recession treated operation sites
      with at least three adjacent Miller Class I and/or II recessions were performed.
      The connective tissue graft obtained from the palatal mucosa was expanded to
      cover the recipient bed, which was 1.5 times larger than the graft. Clinical
      measurements recorded at baseline and 12 months postoperatively included gingival
      recession depth (RD), gingival recession width (RW), percentage root coverage
      (RC), probing depth (PD), width of keratinized tissue (KT), and clinical
      attachment level (CAL). RESULTS: Twelve months after surgery, a statistically
      significant gain in CAL (3.2 +/- 0.8 mm, P < 0.001) and increase in KT (1.2 +/-
      0.4, P < 0.001) were assessed. In 80% of the treated sites, 100% RC was achieved
      (mean 96%). CONCLUSIONS: The results of this study demonstrated that the use of e
      MCTG technique allowed the treatment of multiple adjacent recessions with
      adequate wound healing and highly predictable root coverage. This procedure can
      be applied favorably in treating multiple gingival recessions in one surgery.

PMID- 15455748
TI  - Two-dimensional angular optical scattering patterns of microdroplets in the mid
      infrared with strong and weak absorption.
AB  - Two-dimensional angular optical scattering (TAOS) patterns of droplets composed
      of a mixture of H2O and D2O are detected in the mid infrared. First, a lens is
      used in the Abbe sine condition to collect a small solid angle of light, where
      the scattering pattern matches well numerical simulations based on Mie theory.
      Next, TAOS patterns from droplets spanning a large (approximately 27pi sr) solid
      angle are captured simultaneously at two wavelengths. The effects of absorption
      are evident in the patterns and are discernible without the need for curve
      matching by Mie theory.

PMID- 15455749
TI  - Toward a spherical spot distribution with 4pi focusing of radially polarized
      light.
AB  - The properties of the focal spot for 4pi focusing with radially polarized light
      are presented for various apodization factors. With a focusing system satisfying
      the Herschel condition, sharp focal spots with almost-perfect spherical symmetry
      (leading to equal axial and transverse resolution) and extremely low sidelobes
      are achieved.

PMID- 15455750
TI  - Coupling semiconductor lasers into single-mode optical fibers by use of tips
      grown by photopolymerization.
AB  - We show that a polymer tip, integrated by free-radical photopolymerization at the
      end of a telecommunication optical fiber, allows high-efficiency coupling between
      the fiber and an infrared laser diode. A coupling efficiency of 70% (1.5-dB loss)
      was achieved. We obtained this result by controlling the radius of curvature of
      the tip, the origin of which is discussed in terms of the photochemical influence
      of oxygen during tip formation. The experimental data were found to be in
      agreement with results of electromagnetic calculations based on the finite
      element method.

PMID- 15455751
TI  - Photonic crystal fiber based evanescent-wave sensor for detection of biomolecules
      in aqueous solutions.
AB  - We demonstrate highly efficient evanescent-wave detection of fluorophore-labeled
      biomolecules in aqueous solutions positioned in the air holes of the
      microstructured part of a photonic crystal fiber. The air-suspended silica
      structures located between three neighboring air holes in the cladding crystal
      guide light with a large fraction of the optical field penetrating into the
      sample even at wavelengths in the visible range. An effective interaction length
      of several centimeters is obtained when a sample volume of less than 1 microL is
      used.

PMID- 15455752
TI  - Stimulated Brillouin scattering frequency-domain analysis in a single-mode
      optical fiber for distributed sensing.
AB  - A numerical and experimental analysis of the stimulated Brillouin scattering in a
      single-mode optical fiber for distributed sensing applications is carried out in
      the frequency domain. The theoretical model describing the Brillouin interaction
      is solved by taking into account the temporal dynamics of the acoustic wave that
      is involved. The simulations and the experimental results reveal the role played
      by the ac component of the acoustic wave, which is responsible for significant
      changes of the small-signal stimulated Brillouin scattering transfer function
      that occur when the modulation frequency rises above the natural Brillouin gain
      spectrum linewidth. One should take these effects into account to perform
      accurate signal processing of frequency-domain signals in high-resolution
      distributed sensing applications.

PMID- 15455753
TI  - Log-normal distribution of pulse amplitudes due to Raman cross talk in wavelength
      division multiplexing soliton transmission.
AB  - The effect of delayed Raman response on soliton collisions in wavelength division
      multiplexing (WDM) transmission systems is investigated. Taking into account the
      stochastic nature of pulse sequences in different frequency channels and the
      Raman-induced cross talk, it is shown that the soliton amplitude is a random
      variable with a log-normal distribution. Moreover, the Raman-induced self
      frequency shift and cross-frequency shift are also random variables with log
      normal-like distributions. These results imply that fluctuations in soliton
      amplitude and frequency induced by soliton collisions in the presence of delayed
      Raman response play an important role in massive WDM transmission.

PMID- 15455754
TI  - Modeling the distributed gain of single--(1050 or 1410 nm) and dual-wavelength-
      (800 + 1050 nm or 800 + 1410 nm) pumped thulium-doped fiber amplifiers.
AB  - The distributed gain of single- and dual-wavelength-pumped thulium-doped fiber
      amplifiers is modeled. The excellent agreement between the model and coherent
      optical frequency domain reflectometry measurements enables us to estimate
      intrinsic loss, branching ratios of fluorescence originating from the 3H4 level,
      and cross sections of upconversion pumping at 1050 and 1410 nm for the Tm3+ ions
      in the fiber. With the branching ratios obtained it is possible to describe
      induced signal absorption when pumping at 800 nm.

PMID- 15455755
TI  - Rapid supersampling of multiframe sequences by use of blind deconvolution.
AB  - Under certain conditions, multiframe image sequences can be processed to produce
      images that achieve greater resolution through image registration and increased
      sampling. This technique, known as supersampling, takes advantage of the
      spatiotemporal data available in an undersampled imaging sequence. In this effort
      the image registration is replaced by application of a fast blind-deconvolution
      technique to remove the motion blur in the upsampled average of the image
      sequence. This method produces a supersampled image with significantly decreased
      computational requirements compared with common methods. The method and simulated
      test results are presented.

PMID- 15455756
TI  - Enhanced two-photon fluorescence excitation by resonant grating waveguide
      structures.
AB  - Enhanced two-photon fluorescence (TPF) spectroscopy with novel high-finesse
      resonant polymeric grating waveguide structures (GWSs) is presented. Under
      resonant conditions the field enhancement at the surface of a GWS can be
      exploited for TPF spectroscopy without the need for highly focused laser
      excitation light. We compare the TPF obtained by placing a drop of
      tetramethylrhodamine (TMR) on top of a GWS with that obtained with TMR on top of
      a glass substrate. Our procedure and results indicate that the detection of TPF
      can be improved by a factor of 10 with resonant GWSs.

PMID- 15455757
TI  - Surface plasmon polariton propagation in nanoscale metal gap waveguides.
AB  - Based on finite-difference time-domain simulation of the propagation
      characteristics of surface plasmon polaritons (SPPs) in optical circuits made
      from metal gap waveguides (MGWs) with nanometric gap widths, we theoretically
      demonstrate that two structures that consist of splitting and recombining MGWs
      and of coupling MGWs can be used as nanoscale Mach-Zehnder interferometers. MGW
      arrays show capabilities for array imaging and for controlling the flow of SPPs.
      Other potential applications of coupling MGWs, as SPP switches, directional
      couplers, and even as a nanoscale counterpart for observing linear and nonlinear
      dynamic behavior of electromagnetic fields, are also predicted and discussed. Our
      results point to an interesting way to manipulate optical signals and provide
      efficient sensing in nanophotonic architectures.

PMID- 15455758
TI  - Passive harmonic mode locking with a high-power ytterbium-doped double-clad fiber
      laser.
AB  - We report passive harmonic mode locking of a high-power Yb-doped double-clad
      fiber laser operating in both the normal- and the anomalous-dispersion regimes
      with a fundamental repetition rate of 20.4 MHz. In the normal-dispersion regime,
      116-fs, 1.7-nJ pulses are emitted at a repetition rate of 102 MHz. The results
      indicate a supermode suppression of more than 60 dB. In the anomalous-dispersion
      regime, 1-ps, 125-pJ pulses are emitted at a higher repetition rate of 408 MHz.

PMID- 15455759
TI  - Bismuth- and aluminum-codoped germanium oxide glasses for super-broadband optical
      amplification.
AB  - Broadband infrared luminescence from bismuth-doped germanium oxide glasses
      prepared by a conventional melting-quenching technique was discovered. The
      absorption spectrum of the glasses covered a wide range from the visible to the
      near-infrared wavelength regions and consisted of five broad peaks below 370,
      500, 700, 800, and 1000 nm. The fluorescence spectrum exhibited broadband
      characteristics (FWHM) greater than 300 nm with a maximum at 1300 nm pumped by an
      808-nm laser. The fluorescence lifetime at room temperature decreased with
      increasing Bi2O3 concentration in the glass. Codoping of aluminum and bismuth was
      indispensable for the broadband infrared luminescence in GeO2:Bi, Al glass.

PMID- 15455760
TI  - Warm-white light-emitting diode with yellowish orange SiALON ceramic phosphor.
AB  - A warm-white light-emitting diode (LED) without blending of different kinds of
      phosphors is demonstrated. An approach that consists of a blue LED chip and a
      wavelength-conversion phosphor is carried out. The phosphor is a newly developed
      yellowish orange CaEuSiAlON ceramic phosphor with high efficiency. The CIE1931
      chromaticity coordinates (x, y) are (0.458, 0.414), the color temperature is 2750
      K, and the luminous efficacy of this LED is 25.9 lm/W at room temperature and
      with a forward-bias current of 20 mA. The chromaticity of the assembled LED is
      more thermally stable than that of a LED with a conventional oxide phosphor
      (YAG:Ce) because of the better thermal stability of the oxynitride phosphor.

PMID- 15455761
TI  - Sample-inverted reflow technique for fabrication of a revolved-hyperboloid
      microlens array in hybrid solgel glass.
AB  - We propose a novel fabrication method, which is referred to as the sample
      inverted reflow technique, to fabricate a refractive microlens array (MLA) with a
      revolved-hyperboloid profile in a solgel material. The fabricated solgel MLA
      demonstrates an excellent smooth profile with a fabrication error much less than
      the difference between the revolved hyperboloid and the spherical surface. In an
      application of coupling a laser diode (LD) to a single-mode fiber (SMF), we
      propose a two-MLA coupling scheme in which two revolved-hyperboloid MLAs are used
      between the LD and the SMF. In this configuration the coupling efficiency
      achieves 81.7% (-0.88 dB).

PMID- 15455762
TI  - Microfluidic laser embedded in glass by three-dimensional femtosecond laser
      microprocessing.
AB  - Microfluidic dye lasers three-dimensionally embedded in glass have been
      fabricated for what is believed to be the first time by integrating micro-optical
      and microfluidic components by use of a femtosecond laser. By pumping the
      microfluidic laser, in which the microfluidic chamber was filled with the laser
      dye Rhodamine 6G dissolved in ethanol, with a frequency-doubled Nd:yttrium
      aluminum garnet laser, lasing action was confirmed by analysis of the emission
      spectra at different pump powers. In addition, by arranging two microfluidic
      chambers serially in the glass, we built a microfluidic twin laser that produces
      an array of two simultaneous laser emissions with one pump laser.

PMID- 15455763
TI  - Fluorescence polarization imaging for delineating nonmelanoma skin cancers.
AB  - We present a method for detecting nonmelanoma skin cancers using exogenous
      fluorescence polarization. We built an automated system that permits exogenous
      fluorescence polarization imaging. It includes a tunable linearly polarized
      monochromatic light source and a CCD camera equipped with a rotating linear
      polarizer and a filter to reject excitation light. Two fluorophores that are
      retained in tumors, toluidine blue and methylene blue, are employed. We
      demonstrate that fluorescence polarization imaging can be used for accurate
      delineation of nonmelanoma cancers. The results suggest that this optical
      technique may be suitable for real-time noninvasive demarcation of epithelial
      cancers.

PMID- 15455764
TI  - Multiphoton polarization and generalized polarization microscopy reveal oleic
      acid-induced structural changes in intercellular lipid layers of the skin.
AB  - We have demonstrated that both multiphoton polarization and generalized
      polarization (GP) microscopy may be combined to characterize the structural
      changes of intercellular lipids in skin. Both polarization and GP (at 440- and
      490-nm emission) images obtained by analysis of Laurdan fluorescence suggest that
      the treatment of oleic acid results in a skin surface with a more random packing
      of lipid molecules, which allows easier water penetration. Our results show that
      combined polarization and GP microscopy can be used to characterize the physical
      and chemical changes in biological structures.

PMID- 15455765
TI  - Spectral triangulation molecular contrast optical coherence tomography with
      indocyanine green as the contrast agent.
AB  - We report a new molecular contrast optical coherence tomography (MCOCT)
      implementation that profiles the contrast agent distribution in a sample by
      measuring the agent's spectral differential absorption. The method, spectra
      triangulation MCOCT, can effectively suppress contributions from spectrally
      dependent scatterings from the sample without a priori knowledge of the
      scattering properties. We demonstrate molecular imaging with this new MCOCT
      modality by mapping the distribution of indocyanine green, a FDA-approved
      infrared red dye, within a stage 54 Xenopus laevis.

PMID- 15455766
TI  - Dual-projection optical diffusion tomography.
AB  - We propose a new approach to optical diffusion tomography that incorporates two
      orthogonal projections. All the data obtained in a double projection measurement
      are treated simultaneously. The second projection improves image quality due to
      the fact that the depth and transverse directions are interchanged. An image
      reconstruction algorithm is derived and illustrated with simulations. It is shown
      that the spatial resolution of images improves by a factor of 4-5 due to the
      second projection.

PMID- 15455767
TI  - Endoscopically compatible near-infrared photon migration probe.
AB  - We have developed a 2.3-mm-diameter fiber-optic probe for near-infrared photon
      migration spectroscopy that can be inserted into the body through an endoscope or
      biopsy needle. This probe is specifically designed to be inserted into a core
      biopsy needle to facilitate optical sampling of lesions during breast needle
      biopsy. This probe was tested on tissue phantoms containing heterogeneities (to
      stimulate breast lesions) of various sizes and optical properties. Under the
      conditions tested, the probe can measure the absorption coefficient to within 30%
      for heterogeneities with radii as small as 10 mm.

PMID- 15455768
TI  - Depth-resolved birefringence and differential optical axis orientation
      measurements with fiber-based polarization-sensitive optical coherence
      tomography.
AB  - Conventional polarization-sensitive optical coherence tomography (PS-OCT) can
      provide depth-resolved Stokes parameter measurements of light reflected from
      turbid media. A new algorithm that takes into account changes in the optical axis
      is introduced to provide depth-resolved birefringence and differential optical
      axis orientation images by use of fiber-based PS-OCT. Quaternion, a convenient
      mathematical tool, is used to represent an optical element and simplify the
      algorithm. Experimental results with beef tendon and rabbit tendon and muscle
      show that this technique has promising potential for imaging the birefringent
      structure of multiple-layer samples with varying optical axes.

PMID- 15455769
TI  - Noncontact measurement of nerve displacement during action potential with a dual
      beam low-coherence interferometer.
AB  - We have used a novel phase-referenced heterodyne dual-beam low-coherence
      interferometer to perform what we believe are the first noncontact measurements
      of surface motion in a nerve bundle during the action potential. Nerve
      displacements of approximately 5-nm amplitude and approximately 10-ms duration
      are measured without signal averaging. This interferometer may find general
      application in measurement of small motion in cells and other weakly scattering
      samples.

PMID- 15455770
TI  - Second-harmonic microscopy of unstained living cardiac myocytes: measurements of
      sarcomere length with 20-nm accuracy.
AB  - We extend second-harmonic generation (SHG) microscopy to the measurement of
      sarcomere length in unstained living cardiac myocytes with 20-nm accuracy. We
      quantify individual sarcomere shortening in the presence of saxitoxin and find
      that it is in agreement with mechanical measurements of atrial tissue
      contracture. This functional application of SHG microscopy is generally
      applicable to quantify the physiological effects of drugs on contractile tissue.
      Our data also suggest that packed myosin heads in sarcomere thick filaments are
      responsible for the large second-harmonic endogenous signal in muscle tissue.

PMID- 15455771
TI  - Experimental proof of the feasibility of using an angled fiber-optic probe for
      depth-sensitive fluorescence spectroscopy of turbid media.
AB  - An angled fiber-optic probe that facilitates depth-sensitive fluorescence
      measurements was developed for enhancing detection of epithelial precancers. The
      probe was tested on solid, two-layered phantoms and proved to be effective in
      selectively detecting fluorescence from different layers. Specifically, a larger
      illumination angle provides greater sensitivity to fluorescence from the top
      layer as well as yielding an overall higher fluorescence signal. Monte Carlo
      simulations of a theoretical model of the phantoms demonstrate that increasing
      the illumination angle results in an increased excitation photon density and,
      thus, in increased fluorescence generated in the top layer.

PMID- 15455772
TI  - Phantom validation and in vivo application of an inversion procedure for
      retrieving the optical properties of diffusive layered media from time-resolved
      reflectance measurements.
AB  - An experimental validation of an inversion procedure for retrieving the optical
      properties of layered media from multidistance time-resolved reflectance
      measurements is presented. The results cover a wide range of optical properties,
      showing excellent effectiveness and reliability of the procedure in
      reconstructing the optical properties of a two-layered medium. The optical
      properties of the first layer and the absorption of the second layer could be
      retrieved with excellent precision, whereas the reduced scattering coefficient of
      the second layer was reconstructed with a large error. The first layer thickness
      could be retrieved with an error less than 50%. An example of retrieval of the
      optical properties of muscle from in vivo measurements during an arterial
      occlusion is shown.

PMID- 15455773
TI  - Geometric depolarization in patterns formed by backscattered light.
AB  - We formulate a framework to extend the idea of Berry's topological phase to
      multiple light scattering, and in particular to backscattering of linearly
      polarized light. We show that the randomization of the geometric Berry's phases
      in the medium leads to a loss of the polarization degree of the light, i.e., to a
      depolarization. We use Monte Carlo simulations in which Berry's phase is
      calculated for each photon path. Then we average over the distribution of the
      geometric phases to calculate the form of the patterns, which we compare with
      experimental patterns formed by backscattered light between crossed or parallel
      polarizers.

PMID- 15455775
TI  - Cascaded nonlinear difference-frequency generation of enhanced terahertz wave
      production.
AB  - Cascaded nonlinear optical interactions are analyzed for their potential to
      overcome quantum-defect related limitations on the efficiency of terahertz wave
      difference-frequency generation. The dispersion of ZnTe permits phase-matched
      production of a series of Stokes lines from two initial near-infrared beams. As
      the pump beams run down the Stokes ladder, the number of terahertz photons
      continually increases. A potential improvement by a factor of 5 is demonstrated
      in a 0.26-cm-long crystal by use of 25-MW/mm2 pumps at a wavelength of 824 nm.

PMID- 15455774
TI  - Absorption and scattering imaging of tissue with steady-state second-differential
      spectral-analysis tomography.
AB  - A novel approach to reconstructing both the absorption and the scattering
      properties of a turbid medium simultaneously from steady-state broadband spectral
      measurements is presented that utilizes second-differential fitting to the water
      spectrum to estimate the optical path length in tissue. Theoretical and
      experimental evidence is provided to demonstrate the robust accuracy of the
      spectroscopy approach and reconstructed absorption images. The steady-state
      broadband CCD system has the potential to provide accurate chromophore imaging
      without the technological complexity of time- or frequency-domain systems.

PMID- 15455776
TI  - Two-dimensional higher-band vortex lattice solitons.
AB  - We study self-localized second-band vortex states in two-dimensional photonic
      lattices and find stable ring solitons whose phase forms an array of
      counterrotating vortices. We also identify composite solitons in which a second
      band vortex is jointly trapped with a mode arising from the first band and study
      their stability. When such a composite entity is unstable, it disintegrates while
      exchanging angular momentum between its constituents, eventually stabilizing into
      another form of composite soliton.

PMID- 15455777
TI  - Degenerate four-wave mixing spectroscopy based on two-dimensional femtosecond
      pulse shaping.
AB  - We report noncollinear, degenerate four-wave mixing experiments that employ a new
      device based on two-dimensional femtosecond pulse shaping that delays and
      modulates all incident fields. Heterodyne detection is easily implemented due to
      the full phase stability of the device.

PMID- 15455778
TI  - Cross talk in photochemical three-dimensional optical recording.
AB  - It is shown that the cross talk in three-dimensional optical photochemical
      recording results in ineffectiveness of single-photon recording. For two-photon
      recording for a given allowed cross-talk level there are optimal distances
      between spots that provide the maximum memory density. Estimations show that real
      restrictions here are connected with the reading of information.

PMID- 15455779
TI  - One-off writing of multimicrogratings on glass by two interfered femtosecond
      laser pulses.
AB  - Multimicrogratings are one-off written on silicate glass by two interfered
      femtosecond pulsed laser beams with the aid of a mask. The period and depth of
      the multimicrogratings are revealed by optical microscopy and atomic force
      microscopy. The depth is dependent on both the colliding angle between the two
      interfered laser beams and the laser pulse energy, but the period relies on the
      colliding angle only. We also observe a series of grooves formed at the middle of
      each bulge of the multimicrogratings and attribute it to the higher-order
      modulation arising from second-harmonic generation of the femtosecond laser pulse
      during the one-off writing processes.

PMID- 15455780
TI  - Three-dimensional woodpile photonic crystal templates for the infrared spectral
      range.
AB  - High-quality templates of three-dimensional woodpile photonic crystals are
      fabricated in photoresist SU-8 by use of femtosecond laser lithography. The
      samples have smooth surfaces, are mechanically stable, and are resistant to
      degradation under environmental and chemical influences. Fundamental and higher
      order photonic stopgaps are identified in the wavelength range 2.0-8.0 microm.
      These templates can be used for subsequent infiltration by optically active or
      high-refractive-index materials.

PMID- 15455781
TI  - Ultraslow bright and dark optical solitons in a cold three-state medium.
AB  - We show the formation of ultraslow bright and dark optical solitons in a lifetime
      broadened three-state atomic system under Raman excitation. We also discuss why
      such ultraslow optical solitons may not exist under the conditions of the usual
      electromagnetically induced transparency configuration where zero one- and two
      photon detunings are required.

PMID- 15455782
TI  - Defect modes in photonic crystal slabs studied using terahertz time-domain
      spectroscopy.
AB  - We describe broadband coherent transmission studies of two-dimensional photonic
      crystals consisting of a hexagonal array of air holes in a dielectric slab in a
      planar waveguide. By filling several of the air holes in the photonic crystal
      slab, we observe the signature of a defect mode within the stop band, in both the
      amplitude and phase spectra. The experimental results are in reasonable agreement
      with theoretical calculations using the transfer matrix method.

PMID- 15455783
TI  - 400-photon-per-pulse ultrashort pulse autocorrelation measurement with
      aperiodically poled lithium niobate waveguides at 1.55 microm.
AB  - We demonstrate ultrasensitive intensity autocorrelation measurements of
      subpicosecond optical pulses in the telecommunication band by using aperiodically
      poled lithium niobate (A-PPLN) waveguides. The tightly confined optical beam in
      the waveguides and the chirped poling period facilitate simultaneous high second
      harmonic generation (SHG) efficiency and broad phase-matching (PM) bandwidth. The
      resulting measurement sensitivity is 3.2 x 10(-7) mW2, approximately 500 times
      better than the previous record for intensity autocorrelations. We also show that
      chirped A-PPLN waveguides retain nearly the same SHG efficiency as the unchirped
      guide as long as the PM bandwidth is not significantly broader than the input
      spectrum.

PMID- 15455784
TI  - Ultrashort-pulse Yb3+-fiber-based laser and amplifier system producing >25-W
      average power.
AB  - We have demonstrated an ultrashort-pulse Yb3+-fiber laser and amplifier system
      that produces >400-nJ pulses at a repetition rate of 62 MHz (>25-W average
      power). The output pulses were recompressed to a duration of 110 fs with good
      pulse quality by use of a standard bulk grating-based compressor.

PMID- 15455785
TI  - Femtosecond synchronization of radio frequency signals with optical pulse trains.
AB  - A synchronization scheme for extraction of low-jitter rf signals from optical
      pulse trains, which is robust against photodetector nonlinearities, is described.
      The scheme is based on a transfer of timing information into an intensity
      imbalance of the two output beams from a Sagnac loop. Sub-100-fs timing jitter
      between the extracted 2-GHz rf signal and the 100-MHz optical pulse train from a
      mode-locked Ti:sapphire laser is demonstrated.

PMID- 15455786
TI  - Generation of picosecond hard-x-ray pulses in a femtosecond-laser-driven x-ray
      diode.
AB  - The temporal characteristics of ultrashort hard-x-ray pulses generated in a
      femtosecond-laser-driven x-ray diode are investigated for what is believed to be
      the first time. Copper Kalpha x-ray pulses with a duration of a few picoseconds
      are measured with a jitter-free x-ray streak camera.

PMID- 15455787
TI  - Circular involute stage.
AB  - We report the design and testing of a circular involute stage for high-repetition
      rate (hundreds of hertz), fine temporal resolution (better than 10 fs), and long
      delay range (as great as nanoseconds) time-resolved optical experiments. This
      stage uses a reflector with the involute profile of a circle as well as a pair of
      optical mirrors mounted upon a rotating plate to guide the optical beam,
      following the tangent of the circle. This circular involute stage provides
      unprecedented performance for optical interference, high-resolution terahertz
      time-domain spectroscopy, and general optical pump-probe experiments.

PMID- 15455788
TI  - [Physiological effects of C-peptide].
AB  - Connecting peptide (C-peptide) is a product of proinsulin cleavage. New findings
      demonstrate, that it may serve to understand the mechanisms involved in the
      development of long-term complications in type 1 diabetic patients. The present
      review focuses on: 1. Making a point about C-peptide-induced tubular effects on
      the basis of clinical and experimental experiments, 2. Precising the molecular
      mechanisms involved in C-peptide-induced tubular Na,K-ATPase effects.

PMID- 15455789
TI  - [Drug-induced nephrotoxicity. Bibliography from January to December 2003].

PMID- 15455790
TI  - [Carbonic anhydrase inhibitors and calcium phosphate stones].
AB  - We report a case of a 33 years old female with a history of paroxystic
      hemidystonia treated by acetazolamide, a carbonic anhydrase inhibitor (CAI), and
      who developed two years after the initiation of this treatment bilateral radio
      opaque stones. Laboratory tests revealed a hyperchloremic acidosis, an elevated
      urinary pH, a hypercalciuria, a severe hypocitraturia and numerous granulations
      of amorphous carbonated calcium phosphates and brushite crystals on urinary
      microscopic examination, the whole suggests a diagnosis of acetazolamide-induced
      nephrolithiasis. We discuss in this article the lithogenetic process and the
      usual composition of the stones induced by CAI, and specific risk factors for
      developing drug-induced lithiasis which should be taken into consideration when
      prescribing long-term drug regimens.

PMID- 15455791
TI  - [Efficacy of a pre-dialysis clinic].
AB  - For many years now, the population in Quebec, Canada and other countries, counts
      more and more patients with renal insufficiency and also many more in need of
      dialysis treatments. In Quebec, there are 34 dialysis centres, mostly set in
      short term hospital settings. The two most standard treatments are haemodialysis
      and peritoneal dialysis. Dialysis centres are the most expensive to run and lack
      sufficient funding. Traditional haemodialysis treatments and their related costs
      sums up to 85,000 dollars, per patient, yearly. Terminally ill patients with
      chronic renal insufficiency represent a incompressible practice. If the number of
      patients keeps growing, at the actual rate, we will face a clientele increasing
      from 2200 to 5680 by the year 2006. In 1994, the Health and Social Welfare
      Ministry asked to three socio-sanitary regions to establish a prevention program
      structured in a way to help prevent and slow renal insufficiencies at every
      stages of the illness. This article describes this program and presents the
      results of a research made on the efficacy of these renal insufficiency clinics.

PMID- 15455792
TI  - [A patient with visceral leishmaniasis and acute renal failure in necrotizing
      glomerulonephritis].
AB  - Renal involvement is an unusual complication of human visceral leishmaniasis
      (VL). The kidney lesions are characterized more by interstitial damage than
      glomerular or vascular damage. This case represents a 20 years-old man admitted
      with pancytopenia, purpura, acute renal failure, and nephrotic syndrome
      associated with heavy proteinuria. The diagnosis of VL was made on bone marrow
      smear cytology where Leishmania amastigotes were found. The renal biopsy revealed
      a segmental necrotising glomerulonephritis with 70% crescents. Treatment with
      liposomal amphotericine B alone has been ineffective on the course of renal
      failure, however, partial recovery was obtained after the administration of high
      dose corticosteroids. We present the various clinical, biological, and
      histological aspects of this case, from the south of France. It gave us the
      opportunity to discuss these unusual manifestations of immunomediated necrotising
      skin and renal lesions.

PMID- 15455793
TI  - Standard for clinical electroretinography (2004 update).

PMID- 15455794
TI  - Visual evoked potentials standard (2004).

PMID- 15455795
TI  - Alterations in electroretinograms and retinal morphology in rabbits treated with
      vigabatrin.
AB  - PURPOSE: To determine whether long-term treatment with the anti-epileptic drug
      vigabatrin causes damage to rabbit retina. METHODS: Five rabbits were treated
      continuously with a daily dose of vigabatrin solution per orally during a period
      of 1-8 months. Two rabbits receiving water were used as controls. Repeated full
      field electroretinograms (every two weeks) were assessed during this period.
      Vigabatrin serum concentration was repeatedly measured for securing successful
      drug administration. After termination of treatment the rabbits were sacrificed
      and the morphology of the sectioned retina was studied. RESULTS: In all rabbits
      treated with vigabatrin the serum analyses repeatedly demonstrated elevated drug
      concentration. Full-field electroretinograms demonstrated normal rod function in
      all treated rabbits, but reduced cone function in two of the five treated rabbits
      verified by 30Hz flicker stimulation. Morphologic studies of the sectioned retina
      demonstrated GFAP immunoactivity of the glial cells localized in the retinal
      periphery in all five treated rabbits, one of which had staining also in the
      centrally localized glial cells. The treated rabbits also demonstrated a weaker
      GAD staining in the IPL and less positive amacrine cells, compared to the
      controls. Only two treated rabbits had normal GABA staining while three had an
      enhanced GABA immunoreactivity and undistinguishable fibers in the IPL. In three
      out of five treated rabbits the Muller cells were short, stubby and fragmented,
      with swollen endfeet. CONCLUSION: This study demonstrates changes in
      histopathology caused by vigabatrin in an animal model, which has not been
      reported previously. We have found that vigabatrin orally administrated to
      rabbits does not affect rod function but may reduce cone function in the full
      field electroretinogram, which is similar to the previously reported vigabatrin
      effect on the human ERG. The results indicate that vigabatrin may damage or
      influence, at least one cell type in the rabbit retina.

PMID- 15455796
TI  - A comparison of ERG abnormalities in XLRS and XLCSNB.
AB  - Dark and light adapted ERGs were recorded in 19 patients with XLRS and in 15
      patients with CSNB. Patients were assigned to clinical groups after
      identification of mutations in the RS1 (16 patients), NYX (11 patients) and
      CACNA1F (4 patients) genes causing XLRS, 'complete' CSNB and 'incomplete' CSNB,
      respectively. ERG responses were compared with those of 26 healthy volunteers.
      Rod responses were most severely affected in patients in the NYX group but a rod
      generated b-wave could be identified in the majority of patients in this group.
      Rod responses were less severely affected in the CACNA1F and RS1 groups and ERGs
      did not differ significantly between these two groups. Cone reponses were largely
      unaffected in the NYX group but were abnormal in the RS1 and especially CACNA1F
      groups. The ERG results suggest that the RS1 and CACNA1F gene products have
      comparable functional consequences and that all three genes may affect multiple
      retinal sites.

PMID- 15455797
TI  - Visual electrophysiologic findings in patients from an extensive Brazilian family
      with Leber's hereditary optic neuropathy.
AB  - Leber's hereditary optic neuropathy (LHON) is a maternally inherited disease,
      associated with mitochondrial DNA (mtDNA) point mutations and characterized by
      bilateral, usually sequential, rapid loss of central vision. The purpose of this
      study was to investigate electrophysiologically a small cohort of members from an
      extensive Brazilian family affected by LHON. Pattern-reversal visual evoked
      potentials (PVEP), and full-field electroretinograms (ERG) were performed on the
      four index members, all carrying the 11778 homoplasmic mtDNA mutation. They were
      a 14-year-old recently affected male, his unaffected mother, and her two affected
      brothers. The three affected members all had bilateral profound visual loss with
      visual acuities that ranged from 20/250 to CF, cecocentral defects, and severe
      dyschromatopsia (by FM-100). The unaffected (carrier) female had normal visual
      acuities, visual fields and color discrimination. Severely prolonged P100
      latencies and decreased N75-P100 peak amplitudes were found in pattern-reversal
      VEPs for three affected members. Normal PVEP responses were found in the carrier
      female. Rod and cone ERG responses were normal in two affected members, but both
      the carrier mother and her affected son showed reduced peak-to-peak amplitude for
      single-flash cone response and 30 Hz flicker, with normal b-wave implicit times.
      Thus, optic nerve function, evaluated by PVEP, was severely reduced in LHON
      affected members and normal in the carrier female. However, reduced ERG cone
      responses suggest that LHON can also affect retinal elements, even in the absence
      of fundus and other clinical changes that constitute the full and classical
      expression of LHON.

PMID- 15455798
TI  - Characteristics of first and second order kernels of visually evoked potentials
      elicited by pseudorandom stimulation.
AB  - The characteristics of the first and the second order kernels of the visually
      evoked potentials (VEPs) elicited by pseudorandom binary sequence (PRBS) stimuli
      were investigated. VEPs were recorded from six eyes of four normal volunteers.
      The effects of stimulus luminance on the latency and amplitude of the first and
      the second order kernels were determined. The temporal interactions of transient
      VEPs elicited by single and double pulse stimuli were compared with the first and
      the second order kernels of the PRBS-VEPs. The correlation coefficient between
      the logarithm of the stimuli luminance (log I) and VEP amplitude of the first
      order kernels was 0.45 (p < 0.05), and that between log I and P1 latency was 
      0.62 (p < 0.005). The second order kernels were not equal to the temporal
      interactions of the responses. However, the latency of the negative peak of the
      fourth slice was similar to the temporal interaction to double pulse stimulation
      with an inter-stimulus interval of 40 ms. An inhibitory component at 40 ms
      following the first stimulus was detected in the analysis of both PRBS-VEPs
      second order kernel and transient VEPs. This function may help to increase the
      frequency of critical flicker fusion in normal subjects.

PMID- 15455799
TI  - Are circadian variations in the electroretinogram evident on routine testing?
AB  - We sought to determine whether routine ERGs using ISCEV standard stimuli, would
      show a pattern of circadian variation. We examined ERGs from 40 successive normal
      subjects who were tested at different times during regular laboratory operating
      hours of 9 am to 4 pm, and also reviewed high intensity a-waves from a subgroup.
      There were no obvious associations of either ERG amplitude or implicit time with
      time of day. No statistically significant difference was found between average
      ISCEV ERG parameters or high-intensity a-wave parameters obtained in the morning
      (9 am to 1 pm) and afternoon (1 pm to 4 pm). We conclude that time of day is not
      critical for routine ERG recordings, although small, variable, circadian changes
      may well be present. We suggest that the time of day be noted on clinical
      recordings, in case this information becomes relevant for a particular patient.

PMID- 15455800
TI  - Addressing the in-between generation.

PMID- 15455801
TI  - Aggressive diabetes therapy: is it "best practice?".

PMID- 15455802
TI  - Unnecessary use of ceftriaxone?

PMID- 15455803
TI  - Beware of "natural" products.

PMID- 15455804
TI  - Using corticosteroids during pregnancy. Are topical, inhaled, or systemic agents
      associated with risk?
AB  - QUESTION: I am concerned about use of corticosteroids during pregnancy. Some of
      my women patients of reproductive age are using topical, inhaled, or oral
      preparations, and I am not sure what to advise. ANSWER: Both topical and systemic
      corticosteroids are used for a variety of autoimmune and inflammatory conditions.
      Results of first-trimester studies were inconclusive and underpowered. Recent
      meta-analyses suggest a small but significant association between use of systemic
      corticosteroids during the first trimester and oral clefts. This is consistent
      with results of animal studies. No similar evidence exists for topical or inhaled
      corticosteroids, probably because of much lower systemic exposure.

PMID- 15455805
TI  - Docter-patient communication: taking time to save time.

PMID- 15455806
TI  - Statins' role in prevention. Do statins have a role in primary prevention of
      cardiovascular events?

PMID- 15455807
TI  - Heart attack patients with complications. Treat with valsartan, captopril, or
      both?

PMID- 15455808
TI  - An approach to spider bites. Erroneous attribution of dermonecrotic lesions to
      brown recluse or hobo spider bites in Canada.
AB  - OBJECTIVE: To dispel prevalent myths surrounding diagnosis of dermonecrotic and
      associated conditions supposedly resulting from bites of brown recluse, hobo, or
      other spiders in Canada. SOURCES OF INFORMATION: Worldwide, spider bites are
      regularly misdiagnosed as the etiologic agents in human dermonecrosis mainly as a
      result of inaccurate, erroneous, or hyperbolic popular and professional
      literature based on inference, circumstantial evidence, inferior clinical trials,
      and misunderstanding of the facts regarding spider-bite envenomation. MAIN
      MESSAGE: A working diagnosis of "spider bite" or publishing a case history should
      be considered only when a spider is caught in the act of biting or otherwise
      reliably associated with a lesion. Accurate identification of the spider could be
      critical for correct diagnosis and subsequent treatment. CONCLUSION: Brown
      recluse spiders are not found in Canada. Hobo spiders have not been reliably
      implicated in dermonecrosis. Worldwide, spider-bite envenomation is an unlikely
      cause of dermonecrosis. Canadian physicians should give priority consideration to
      other, more likely, causes.

PMID- 15455809
TI  - Inhaler therapy. What it means for children with asthma.
AB  - OBJECTIVE: To investigate what inhaler therapy means for children with asthma and
      to identify problems and concerns children experience with inhalers. DESIGN:
      Qualitative research design. SETTING: A community-based family practice in rural
      Newfoundland. PARTICIPANTS: Seventeen children, aged 5 to 16, who had been
      diagnosed with mild or moderate asthma and were being prescribed inhaled steroids
      or bronchodilators. METHOD: Two in-depth interviews with each of a purposive
      sample of participants were analyzed by the selective or highlighting approach.
      MAIN FINDINGS: Common positive themes were identified: inhalers were easy to use,
      and medication was necessary for good quality of life. Common negative themes
      were simply forgetting, inconvenient and annoying, only-as-needed approach,
      medication does not work well anyway, and side effects. CONCLUSION: Inhaler
      therapy had both positive and negative meaning for children. Although inhaled
      medications were seen as very important for good quality of life when taken
      regularly, most children wanted to use them only as needed for symptom control.
      Children knew the importance of inhaler therapy but still complied poorly.

PMID- 15455810
TI  - Outcomes after vacuum-assisted deliveries. Births attended by community family
      practitioners.
AB  - OBJECTIVE: To assess success rates, modes of delivery following failure,
      complications of mothers and newborns, and effect of extractor station and parity
      on vacuum-assisted deliveries attended by family physicians. DESIGN:
      Retrospective audit. SETTING: Community hospital. PARTICIPANTS: Thirty-five
      family physicians providing maternity care. MAIN OUTCOME MEASURES: Complications,
      parity, and extractor station of 153 vacuum-assisted deliveries from April 1,
      2000, to March 31, 2003. RESULTS: Family physicians attempted 153 vacuum
      deliveries (82 at low station, 71 at outlet station) and had a 94.1% success
      rate. Of nine failed vacuum deliveries (eight at low station and one at outlet
      station), four were subsequently delivered by forceps and five by cesarean
      section. Except for one case of subdural hematoma, complications were few.
      Nulliparity was associated with six of the nine failed vacuum deliveries.
      CONCLUSION: Family physicians were usually successful with vacuum-assisted
      deliveries. Complications were infrequent and rapidly resolved, but one failure,
      which was followed by a failed forceps delivery and eventual cesarean section,
      resulted in a serious complication. Low station and nulliparity were associated
      with failure of vacuum-assisted deliveries.

PMID- 15455811
TI  - Adverse drug reactions in Canada. Hematologic reactions to sterol and sterolin
      containing products.

PMID- 15455812
TI  - Expert evidence and testimony: Daubert versus Frye.

PMID- 15455813
TI  - [A monitor of the biomechanical cardiac activity].
AB  - A monitor of the biomechanical cardiac activity is described, which was
      elaborated on the basis of the accelerometer sensor and sigma-delta ADC for the
      purpose of registering the ballistocardiograms and seismocardiograms. The device
      ensures a non-stop signal recording for as long as 8 hours with the data being
      preserved in an inbuilt memory. Data are fed to the computer through the USB
      port. An algorithm is suggested for recordings processing by using the neuron-net
      technologies.

PMID- 15455814
TI  - [Physical problems in the medical X-ray computer tomography].
AB  - Physical models related with solution approximation of a transport equation
      applicable to X-ray computer tomography are under discussion. Use of a point mono
      energy collimated irradiation source is defined; when such source interacts with
      an investigated object, the effect of scattering of primary photons can be
      neglected or considered for the general tendency of rectilinear propagation of
      photons in a substance. The model can be adopted for photon energies ranging from
      20 to 150 keV, in which a weak effect from Compton scattering and photoeffect
      predominance are evident.

PMID- 15455815
TI  - [Spectrozonal X-ray detector].
AB  - The design of a spectrozonal X-ray detector is described. Choice of spectral
      ranges for reproducing the color separation of X-ray images is under discussion.
      The research results of dependence of the quantum efficiency of registration of
      the spectrozonal detector on the quantum energy of X-ray radiation and on the
      design parameters of the converter are presented.

PMID- 15455816
TI  - [An information-and-measurement system for multi-parameter evaluation of the
      condition of the human locomotor apparatus].
AB  - The authors created the hardware and software for evaluating the human locomotor
      functions. The equipment is designed for monitoring the rehabilitation of
      patients who lost their motor functions due to trauma or illness as well as for
      monitoring the efficiency of athletes' training. The structure and possibility to
      adapt the set to fulfilling other tasks are among the equipment advantages.

PMID- 15455817
TI  - [Electric stimulator for the gastrointestinal tract].
AB  - A theoretical possibility of creating an autonomous electric stimulator for the
      gastrointestinal tract is discussed. The feasibility of using a galvanic element
      with two dissimilar electrodes and gastrointestinal medium instead of the
      intravenous power source (galvanic battery) is contemplated.

PMID- 15455818
TI  - [Bactericidal and biologically stable coatings for medical implants and
      instruments].
AB  - The experimental research showed the fine-film coating based on hafnium nitride
      to inhibit the pathogenic microflora and to exert the bactericidal effect by far
      less versus that of antibiotics; at the same time, the concentration of hafnium
      ions in the solution is just within the sensitivity limit detectable by the most
      recent registration methods--it amounts to less than 10(-10) mol/l. Therefore,
      according to the research results, the use of such coatings based on hafnium
      nitride is promising in manufacturing the surgical metal implants and medical
      instruments.

PMID- 15455819
TI  - [A new technology for evaluation the functional condition of the cardiovascular
      system].
AB  - New models of a sensor matrix and of a device designed for biomedical diagnostics
      are described. A radio-induction analysis technique applicable to hemodynamic
      parameters as well as the related equipment and soft meant for evaluating the
      functional condition of the cardiovascular system were elaborated. The
      potentialities of using the above computer system in medical diagnostics are
      defined.

PMID- 15455820
TI  - [Mathematical modeling of optimal dose fields in radiotherapy of malignant
      tumors. Part 2 (Contact methods of radiotherapy)].
AB  - The principles of mathematical modeling of optimal dose fields in contact
      radiotherapy (RT) of malignant tumors are investigated. The point dose additivity
      provides for presetting the permissible dose field in an irradiated organism as a
      system of linear limitations to doses in the control points (CP) distributed in
      the lesion focus and in healthy organs and tissues. It was shown as impossible to
      shape a dose field by linear limitations to doses in CP in using the RT contact
      methods with the irradiation sources being implanted into lesion focus. A
      mathematic interpretation was suggested for the task (with its solution by an
      iterative algorithm) of forming an optimal dose field in the lesion focus with
      implanted irradiation sources, which is based on maximizing the factor of dose
      field homogeneity. It was further demonstrated that linear limitations, if added
      to the dose in healthy organs and tissues, make the task even more complicated if
      not insoluble. Finally, it is suggested to use the method of shaping an effective
      dose field by the iterative method with interactive visual optimization of the
      dose field.

PMID- 15455821
TI  - [A classification of tomography examination methods].
AB  - An analysis of current tomography evolution was performed making it possible to
      classify the tomography tools of object examinations by projections. It was based
      on a position of radiation source, its type and reconstructed position in its
      interaction with a studied object. Significance of X-ray computer tomography
      within the above classification was defined.

PMID- 15455822
TI  - [Russian chemicals designed for processing the radiographic medical films].
AB  - Technical characteristics of Russian chemicals designed for processing the
      radiographic medical films are described in the paper. Requirements applicable to
      operating solutions and films characteristics, obtained by the manual and machine
      processing, are defined. It is demonstrated as feasible to choose the chemicals
      with respect to the economic parameter, i.e. cost per unit of photoprocessing of
      1.0 m2 of film at the photo laboratories of patient-care and preventive
      facilities.

PMID- 15455823
TI  - [Designing and manufacturing of medical equipment by OAO MNPK "Avionika"].
AB  - The paper is dedicated to the activity of Research and Production Enterprise
      "Avionika", a leader in the field of designing and manufacturing of medical
      equipment. Technical data of medical suction units produced by the enterprise
      were comparatively analyzed versus those made by other manufacturers.
      Additionally, failures of suction equipment were analyzed and technical solutions
      enhancing the operational safety are suggested. Promising trends are defined for
      perfecting the discussed equipment type.

PMID- 15455824
TI  - ["Advanced Nursing Practice" is worth while!].

PMID- 15455825
TI  - [Nurse-led heart failure clinics: Swedish experiences of Advanced Nursing
      Practice during 10 years].
AB  - This paper aims at describing the development of nurse-led heart failure clinics
      in Sweden and discusses what effects and possibilities this type of advanced
      nursing practice gives the patients, the health care system and the nurses.
      Follow-up at nurse-led heart failure clinics involve patient education, optimised
      treatment and social support and has been shown to improve survival and self-care
      behaviour in patients with heart failure and reduce the need for hospital care.
      This model of care has spread from Sweden to many European countries, but still
      only a minority of the patients hospitalised due to heart failure receive this
      type of follow-up. It should be considered for several more patients in Europe.
      The organisation of the nurse-led follow-up needs to be adapted to the different
      needs of patients within the heart failure population and to the health care
      system of each country. Formal competence among heart failure nurses needs to be
      continuously improved in order to provide high-quality care to heart failure
      patients. This can be achieved through improved education and increased national
      and international collaboration among heart failure nurses. Networking among
      heart failure nurses on a regional, national and international level is crucial.
      Joint activities such as study visits, national and international working groups,
      conferences, workshops and research collaboration can be important tools in this
      development.

PMID- 15455826
TI  - [Outcomes and experiences of caring for families with children with cleft lip and
      palate at the Children's Hospital of Zurich].
AB  - The development and establishment of Advanced Nursing Practice is an important
      step toward an effective and sustainable care. Five diploma nurses of the
      Children's Hospital of Zurich started an ANP project in the field of children
      with cleft lip and palate under the guidance of an ANP Nurse. The purpose of this
      project was to address the needs of the families and to establish state-of-the
      art care. Action research methodology built the background because it offers
      methods that connect theory and practice. Family management and organizational
      elements (project team, organization and new services) were the basic elements of
      the project. The goal of this paper is to present the first evaluation of this
      project. For instance, today, the families have the opportunity to visit the
      hospital before the first surgery. For the children, pain management and
      nutrition after surgery were adapted to state of the art knowledge. The
      evaluation also shows areas that need to be further developed in the future. The
      results emphasize, that the ANP-team projects with family management as core
      activity empowered the team members and led to an adaptation of nursing practices
      towards the needs of the families.

PMID- 15455827
TI  - [Midwife-led labour in a Swiss hospital].
AB  - A midwife-led labour care model was introduced in a Swiss University Hospital.
      This new model enabled expectant mothers who had a low risk medical history to
      give birth with the support of only a midwife. The model has been evaluated as
      part of a pilot project in a comparative study. A quantitative-explorative design
      was chosen. Labour with only a midwife in comparison with the traditional
      presence of a doctor and a midwife resulted in fewer invasive procedures, while
      the outcome parameters were similar in both groups. The post partum hospital stay
      of the women in the midwife-only group was significantly shorter than in the
      midwife-and-doctor group. The midwife-only model appealed to a certain group of
      women and their partners who generally had a higher level of education. Women in
      both groups were highly satisfied with the midwifery care; the possibility of
      giving birth in hospital with the presence of a midwife alone was very much
      appreciated. Under an economic aspect the results of the study provide
      preliminary indications that delivery by a midwife alone involves lower costs and
      therefore increased income for the hospital in question.

PMID- 15455828
TI  - [A method combination for Advanced Nursing Practice projects].
AB  - In order to offer Advanced Nursing Practice (ANP) in Switzerland, some practice
      development projects have been established with the goal to enable entire nursing
      teams to become ANP Teams. These ANP Teams are led by ANP nurses with a high
      expertise in the specific practice area. The combination of the three methods
      action research, project management and evaluation research have proven useful
      for the ANP nurse as project leader. Action research is viewed as the leading
      force because of its scientific methods that allow focusing on practice problems
      and actions. With project management methods, the ANP project can be organized in
      an effective and efficient way. Evaluation research offers methods to
      systematically evaluate the project at the level of patients, team, and
      organization. The combination of these different methods allows the ANP nurse to
      work systematically and flexibly and improves results.

PMID- 15455829
TI  - [Effective nursing practice--a challenge leading to a practical report of the
      nursing staff of the Children's Hospital in Zurich].

PMID- 15455830
TI  - [The beaten track of professional work].

PMID- 15455831
TI  - Hospitals adopt Toyota principles to drive out infections.

PMID- 15455832
TI  - Vaccination rates boosted from 34% to 63% in one year.
AB  - Summer may seem like a strange time to worry about vaccinating people for
      influenza, but at the Deaconess Billings Clinic in Billings, MT, a performance
      improvement project to increase the vaccination rate continues year-round.

PMID- 15455833
TI  - Effort to standardize physician performance hits high gear.
AB  - The National Quality Forum is leading an alphabet-soup coalition of private and
      public agencies in the effort to develop a national set of ambulatory care
      physician performance measures through the NQF's consensus-building process.

PMID- 15455834
TI  - Analysis, design and implementation of secure and interoperable distributed
      health information systems.

PMID- 15455835
TI  - A framework for considering business models.
AB  - Information technology (IT) such as computerized physician order entry, computer
      based decision support and alerting systems, and electronic prescribing can
      reduce medical errors and improve the quality of health care. However, the
      business value of these systems is frequently questioned. At present a number of
      barriers exist to realizing the potential of IT to improve quality of care. Some
      of these barriers are: the ineffectiveness of existing error reporting systems,
      low investment in IT infrastructure, legal impediments to reforms, and the
      difficulty in demonstrating a sufficient return on investment to justify
      expenditures for quality improvement. This paper provides an overview of these
      issues, a framework for considering business models, and examples of successful
      implementations of IT to improve quality of patient care.

PMID- 15455836
TI  - Health care information technology: better care, better business.
AB  - The health care industry is in crisis. From patient safety concerns to wasteful
      operations to overburdened workforces, health care is ripe for reinvention. In
      "Health Care Information Technology: Better Care, Better Business," Glenn Tobin
      discusses the aspects of health care in need of transformation; the reasons why
      health care information technology is the right solution; and the benefits to be
      realized from implementing IT.

PMID- 15455837
TI  - Choosing the commercially correct idea for research and development. From a
      telemedicine company perspective.
AB  - Healthcare delivery is undergoing major changes in order to reduce spiraling
      costs without sacrificing the quality of care. Patients and consumers are at the
      center of these changes. Telemedicine is growing rapidly. It offers many
      advantages to different healthcare players, yet still faces many entry barriers.
      Medical technology companies developing telemedicine products have to consider
      the market needs, the customer, the product development aspect, the business
      model, and the long process of market penetration, in order to choose the
      commercially correct idea and successfully bring it to the market.

PMID- 15455838
TI  - Mixed messages: legal incentives and disincentives confronting technologically
      mediated care.
AB  - The "systems" approach to reducing medical errors is increasingly viewed as
      dependent upon technology. Issues with the legal system, however, may impede
      needed reforms. Historically there has been a pervasive disconnect between the
      legal system and changes in healthcare business models and structures. Further,
      difficult legal issues will accompany care that is increasingly technologically
      mediated. This chapter identifies some of the most serious disconnects and makes
      suggestions for needed reform.

PMID- 15455839
TI  - Business models for health care decision support.
AB  - CareScience, Inc. is a public company (NASDAQ: CARE) that originated ten years
      ago to commercialize risk adjustment and complication predictions developed by
      the Wharton School of Business and the University of Pennsylvania School of
      Medicine. Over the past decade, the company has grown to approximately 200
      clients and 150 employees. Among the "firsts" recorded by the company,
      CareScience was the first to offer a clinical decision support system as an
      Application Service Provider (ASP), the first to offer peer-to-peer clinical data
      sharing among health care provider organizations and practitioners (Santa Barbara
      Care Data Exchange), and the first to provide a care management outsourcing
      arrangement.

PMID- 15455840
TI  - Current and emerging business models in the health care information technology
      industry: a view from wall street.
AB  - When we think about health care IT, we don't just think about clinical automation
      with the movement to computerized physician order entry (CPOE), but also the need
      to upgrade legacy financial and administrative systems to interact with clinical
      systems. Technology acceptance by physicians remains low, and computer use by
      physicians for data entry and analysis remains minimal. We expect this trend to
      change, and expect increased automation to represent gradual change. The HCIT
      space is dynamic, with many opportunities, but also many challenges. The unique
      nature of the end market buyers, existing business models, and nature of the
      technology makes this a challenging but dynamic area for equity investment.

PMID- 15455841
TI  - Federal initiatives in information technology to improve patient safety and
      quality of care.
AB  - In November 1999, the Institute of Medicine (IOM) released a report that focused
      on patient safety in the United States (U.S.), in which it estimated that up to
      98,000 people die in U.S. hospitals each year from medical errors. In March 2001,
      the IOM released a follow-up report encompassing a broader range of quality
      issues in the U.S. health care system. It concluded that health care in the U.S.
      is plagued by a variety of problems which stem from an outmoded system that does
      not provide high-quality care on a consistent basis. The IOM also outlined a
      strategy for redesigning U.S. healthcare to achieve safe, dependable, high
      quality care, which emphasizes information technology as an integral part of the
      solution. In 2001, the Agency for Healthcare Research and Quality (AHRQ) spent
      $50 million on initiatives to reduce medical errors and improve patient safety.
      The crux of these initiatives was a series of solicitations that form an
      integrated set of research and demonstration projects for reducing medical errors
      in multiple health care settings. This chapter will discuss some of these
      initiatives, focusing on the role of clinical informatics in the Agency's efforts
      to improve the safety and quality of health care in the U.S.

PMID- 15455842
TI  - Developing a shared agenda for health care systems safety and quality.
AB  - High quality, computer-interpretable, patient-specific knowledge at the point of
      need is essential, as we seek to incorporate decision support and other
      approaches in clinical information systems to achieve safety and increased
      quality of health care. This gives rise to the need for shared, standards-based
      approaches to representing the knowledge and tools for management of it.

PMID- 15455843
TI  - Empowering patients: total product life cycle for medical devices.
AB  - Patients today demand a stake in the care of their own health. The expectation is
      that patients who take responsibility for their own care will communicate more
      effectively with their health care team and be productive citizens in our
      society. Medical technology today and those products visible on the horizon,
      coupled in a telehealth network, provide promise to empower patients to
      participate fully in the management of their own health. Technology alone,
      however, will not integrate the elements required for an effective telehealth
      system. This chapter considers the non-technical matters of this issue such as
      trends in the medical device industry, trends in the point of care, public health
      care policies, and the role of government regulation, working together to achieve
      these public health goals.

PMID- 15455844
TI  - A systems approach to preventing adverse drug events.
AB  - It is estimated that over three-quarters of a million people are injured or die
      in hospitals each year from adverse drug events. The majority of medical errors
      result from poorly designed health care systems rather than from negligence on
      the part of health care providers. While there is considerable evidence that
      information technology can be used to significantly reduce medication errors and
      adverse events, information technology, to be effective, must be implemented
      using a systems approach. This paper reviews three studies that have used a
      systems approach to investigate the causes of medication errors and the
      effectiveness of information technology in preventing adverse drug events.
      Significant reduction of medication errors and adverse drug events requires
      systemic implementation of information technology, improvements in the reporting
      of errors, and integration with other systems designed to detect and prevent
      errors.

PMID- 15455845
TI  - Building support for health information technologies.
AB  - Despite the increasing role of information technology in health care, its use
      still lags behind that occurring in other sectors. Factors contributing to this
      include the complex health care environment and conflicting political agendas.
      Building political support for information technology in health care depends on
      understanding the importance of stakeholders and the environment in which they
      operate. It is important to involve stakeholders early in the process of
      implementing new information technology in order to identify needs, barriers, and
      non-starters. Understanding the historical experience of the community and its
      past attempts at using information technology is also important. Quality of care
      issues, nursing shortages, cost control concerns, health insurance costs and
      coverage rates, institutional solvency, and overwhelming paperwork are current
      problems in the healthcare environment that can hinder willingness to invest in
      information technology. Ironically, information technology can also help remedy
      these problems. Impact on workflow, privacy of personal health information, and
      system reliability, interoperability, and the ease of updating the system can all
      have political ramifications with regard to acceptance and implementation of
      information technology.

PMID- 15455846
TI  - Physician practice management solutions.
AB  - Medicine today has changed in many aspects. Physician practices face enormous
      challenges in the form of higher costs, lower reimbursement, and managed care.
      Barriers in the form of physician discomfort with information technology and the
      costs associated with employing this technology make physicians reluctant to
      adopt information technology systems in their practices. Thus the problem is how
      to get doctors to adopt technology that can actually help them combat these
      challenges and problems and provide quality care to patients. This chapter
      discusses an appropriate and practical orientation from which to approach design
      and implementation of information technology for the office practice.

PMID- 15455847
TI  - Citizen Health System: telehealth homecare.
AB  - The Citizen Health System (CHS) is a European Commission (CEC) funded project in
      the field of IST for Health. Its main goal is to develop a generic contact center
      which in its pilot stage can be used in the monitoring, treatment, and management
      of chronically ill patients at home in Greece, Spain, and Germany. Such contact
      centers, using any type of communication technology, and providing timely and
      preventive prompting to the patients, are envisaged in the future to evolve into
      well-being contact centers providing services to all citizens. In this paper, we
      present the structure of such a generic contact center and in particular the
      telecommunication infrastructure, the communication protocols and procedures, and
      finally the educational modules that are integrated into this contact center. We
      present the procedures followed for two target groups of patients, namely
      diabetic patients, and congestive heart failure patients, in which two randomized
      controlled clinical trials are under way. We present examples of the
      communication means between the contact center medical personnel and these
      patients, and elaborate on the educational, user, and telecommunication issues
      involved.

PMID- 15455848
TI  - Telecommunications model for continuing education of health professionals: the
      Royal Brompton case.
AB  - Telemedicine is said to be helpful to both patients and providers, but we need
      real-world examples to demonstrate its effectiveness. This paper presents such an
      example. Royal Brompton, under the Tele-remedy Program of EC Telecom, conducted a
      project with the Children's Hospital of Athens, Greece, to provide remote
      diagnosis management and continuing education for heart disease, using European
      ISDN technology. Preliminary results showed that, when carried out in a large
      scale multi-site environment, Teleremedy program significantly reduced geographic
      and socio-economic isolation for the patient and the professional isolation for
      the physician. Comparison of original vs. transmitted data revealed no
      significant differences, with diagnosis accuracy of 100%.

PMID- 15455849
TI  - Demonstrating the practical value of new health technologies.
AB  - The applications of telemedicine are extremely diverse. They can be categorised
      as follows: teleconsulting, telemonitoring, centralised networked training as
      well as continuing and further education, and information systems. At the heart
      of telemedicine is, of course, the improvement of patient care, including care in
      decentralized parts of the health system. Expertise and therefore quality should
      be brought into the medical care system across the board by medical centers using
      technical aids. Particularly in rural areas, this increases a patient's chances
      of being able to be treated at home, even in the presence of complications or
      relatively rare medical conditions. Modern information and communication
      technologies also allow medical establishments or groups of establishments to
      manage their resources more efficiently. In this paper are presented many ongoing
      telemedicine projects at the University of Regensburg that demonstrate that
      beneficial aspects of telemedicine result not only in verifiable improvements in
      quality of care but also in substantial savings.

PMID- 15455850
TI  - Application of peer-to-peer networking to health care.
AB  - People with chronic illness or disability share similar information needs that
      are not routinely handled by a system designed for traditional health services.
      Recent historical initiatives to provide alternate information systems for
      sharing information or coordinating services have been highly centralized, were
      expensive to set up and were not sustainable. We propose a novel application of
      peer-to-peer networking to provide an infrastructure for information exchange and
      service coordination. The peer-to-peer model empowers the user (citizen with
      disabilities) with control over the type and extent of information about
      themselves that is communicated and to whom. Further, the peer-to-peer model
      leads to a decentralized resource that grows incrementally, supported by the
      users, and is potentially more sustainable.

PMID- 15455851
TI  - Value added telecommunication services for health care.
AB  - The successful implementation and operation of health care networks and the
      efficient and effective provision of health care services is dependent upon a
      number of different factors: Telecommunications infrastructure and technology,
      medical applications and services, user acceptance, education and training,
      product and applications/services development and service provision aspects. The
      business model and market development regarding policy and legal issues also must
      be considered in the development and deployment of telemedicine services to
      become an everyday practice. This chapter presents the initiatives, role and
      contribution of the Greek Telecommunications Company in the health care services
      area and also refers to specific case-studies focusing upon the key factors and
      issues of applications related to the telecommunications, informatics, and health
      care sectors, which can also be the drivers to create opportunities for Citizens,
      Society and the Industry.

PMID- 15455852
TI  - Business models for cost effective use of health information technologies:
      lessons learned in the CHCS II project.
AB  - The Department of Defense (DoD) has embarked on an initiative to create an
      electronic medical record for all of its eligible beneficiaries. The Clinical
      Information Technology Program Office (CITPO) is the joint-service program office
      established to centrally manage this multi-year project. The Composite Health
      Care System II (CHCS II) is the name of the system under development. Given the
      historical failure rate of large-scale government information system projects,
      CITPO has employed an incremental acquisition approach and striven to use
      industry best practices to the greatest degree possible within the constraints of
      federal acquisition law. Based on lessons learned during the concept exploration
      phase of this project, CITPO, in partnership with Integic Corporation, the prime
      integration contractor, has reengineered its software acquisition process to
      include industry best practices. The result of this reengineering process has
      resulted in a reduction of the total projected life cycle costs for CHCS II from
      the original estimate of $7.6 billion over a 14-year period to between $3.9 and
      $4.3 billion.

PMID- 15455853
TI  - Special visual effects for surgical simulation: cauterization, irrigation and
      suction.
AB  - Simulation of cauterization and irrigation forms an important part of a virtual
      laparoscopic trainer. Typically, they are carried out to stop the intragastric
      bleeding due to an accidental cut by the surgeon. In this paper, we present a
      method to simulate these special visual effects in an integrated fashion in real
      time. We have simulated cauterization and irrigation using a particle-based
      system. A physics-based model is used to simulate accumulation and removal of
      fluids. The integrated special effects were implemented and tested in a prototype
      environment.

PMID- 15455854
TI  - A haptic model of a bone-cutting burr.
AB  - We describe a strategy for collecting experimental data and validating a bone
      burr haptic contact model developed in a virtual surgical training system for
      middle ear surgery. The validation strategy is based on the analysis of data
      acquired during virtual and real burring sessions. Our approach involves
      intensive testing of the surgical simulator by expert surgeons and trainees as
      well as experimental data acquisition in a controlled environment.

PMID- 15455855
TI  - Mixed reality for neurosurgery: a novel prototype.
AB  - Microscopes and neuronavigators are often used in neurosurgical procedures. Our
      Mixed Reality prototype proposes to show neuronavigator imaging overlayed onto
      the surgical field of view. The proposal is to replace the traditional optical
      microscope with a digital one. The system is presented in this article. Firsts
      trials have been performed at the laboratory with satisfactory results.

PMID- 15455856
TI  - GeRTiSS: Generic Real Time Surgery Simulation.
AB  - Minimally invasive surgery is a technique that permits interventions through very
      small incisions. This minimises the patients' trauma and permits a faster
      recovery in comparison with classical surgery. The disadvantage of this surgery
      technique, though, is its complexity, requiring a high training effort of the
      surgeon. In this paper, we present a general surgery simulator for training
      surgeons in minimally invasive surgery. The application allows to create
      environments and interaction modes very similar to those encountered in real
      surgical interventions. The virtual environments are optionally composed of an
      actual patient's organs the intervention on which one desires to practice in a
      beforehand manner, or of synthetically generated organs with arbitrary
      pathologies. The intervention is carried out by means of haptic interfaces with
      force feedback, providing the surgeon with a sense of touch, a fundamental
      element of all types of surgery.

PMID- 15455857
TI  - Simulating needle insertion and radioactive seed implantation for prostate
      brachytherapy.
AB  - We are developing a simulation of needle insertion and radioactive seed
      implantation to facilitate surgeon training and planning for brachytherapy for
      treating prostate cancer. Inserting a needle into soft tissues causes the tissues
      to displace and deform: ignoring these effects during seed implantation leads to
      imprecise seed placements. Surgeons should learn to compensate for these effects
      so seeds are implanted close to their pre-planned locations. We describe a new 2
      D dynamic FEM model based on a 7-phase insertion sequence where the mesh is
      updated to maintain element boundaries along the needle shaft. The locations of
      seed implants are predicted as the tissue deforms. The simulation, which achieves
      24 frames per second using a 1250 triangular element mesh on a 750Mhz Pentium III
      PC, is available for surgeon testing by contacting ron@ieor.berkeley.edu.

PMID- 15455858
TI  - In-vivo and in-situ compressive properties of porcine abdominal soft tissues.
AB  - Accurate biomechanical characteristics of tissues are essential for developing
      realistic virtual reality surgical simulators utilizing haptic feedback. Surgical
      simulation technology has progressed rapidly but lacks a comprehensive database
      of soft tissue mechanical properties with which to incorporate. Simulators are
      often designed purely based on what "feels right;" quantitative empirical data
      are lacking. A motorized endoscopic grasper was used to test abdominal porcine
      tissues in-vivo and in-situ with cyclic and static compressive loadings. An
      exponential constitutive equation was fit to the resulting stress-strain curves,
      and the coefficients were compared for various conditions. Stress relaxation for
      liver and small bowel were also examined. Differences between successive squeezes
      and between in-vivo and in-situ conditions were found.

PMID- 15455859
TI  - A VR-system supporting symmetry related cranio-maxillofacial surgery.
AB  - The reconstruction of patients with large deformations in the facial area should
      consider functional aspects as well as aesthetical ones. In this paper, an
      integrated virtual reality system which allows bone manipulation, osteotomy
      planning, calculation of implants for soft tissue and bones combined with the
      calculation of the post-operative appearance is presented. It is a valuable tool
      for a wide range of cranio-maxillofacial surgeries. Due to the generalized
      approach of the underlying algorithms, it is a basis for further clinical
      applications in other surgical fields.

PMID- 15455860
TI  - Analyzing the MMVR research space: past emphases, future directions.
AB  - The MMVR Conference is one of a handful of national forums where leading
      researchers regularly convene to discuss medical modeling and simulation. As
      such, the presentations made during the conference represent a reasonable
      overview of both the state-of-the-art in virtual reality in medicine and the
      basic and applied research trends in the field. This article describes those
      trends and some of the implications based on a meta-analysis of almost three
      hundred articles published as a result of the MMVR Conferences in 2000, 2001, and
      2002.

PMID- 15455861
TI  - Online training evaluation in VR simulators using Gaussian Mixture Models.
AB  - A new approach to evaluate training in simulators based on virtual reality is
      proposed. This approach uses Gaussian Mixture Models (GMM) for modeling and
      classification of the simulation in pre-defined classes of training.

PMID- 15455862
TI  - Quantifying expert vs. novice skill in vivo for development of a laryngoscopy
      simulator.
AB  - Many medical procedures require fine motor skills, and these skills are developed
      over years of practice and through performing hundreds to thousands of
      procedures. However medical training that is based upon gaining this expertise by
      performing procedures on patients results in unnecessary risk to the patient. In
      this project expert medical skill is quantified, so that advanced medical
      simulators can be created to provide a realistic training environment. This
      approach is applied to airway intubation with a rigid laryngoscope; a procedure
      that is performed prior to general anesthesia and during emergency situations. A
      laryngoscope has been instrumented with a 3 dimensional force/torque sensor, and
      magnetic position sensors have been placed on the laryngoscope and the patient.
      Measurements are made in the operating room of both experts and novices as they
      perform laryngoscopy on consenting patients undergoing general anesthesia. The
      skill of the laryngoscopist is represented by the motion and force trajectories
      applied to the laryngoscope during the procedure. Preliminary results show that
      novices often err in the placement of the tip of the laryngoscope blade. However,
      when two experts perform laryngoscopy on the same patient, both experts perform
      key elements of the task consistently. The measured consistency among experts
      indicates that it will be possible to apply algorithms developed for Human Skill
      Acquisition, and thereby define regions of expert motion relative to patient
      anatomy. This is the first step in developing advanced training simulators that
      will simulate the procedure accurately, provide guidance to the trainee, and can
      be used for assessment of medical skill.

PMID- 15455863
TI  - Modelling human burn injuries in a three-dimensional virtual environment.
AB  - This paper gives a work-in-progress report on our research project BurnCase, a
      virtual environment for modelling human burn injuries. The goal of the project is
      to simplify and improve the diagnosis and medical treatment of burns. Due to the
      lack of electronic and computational support for current diagnosis methods,
      enormous variations regarding the approximated size of burned skin regions exist.
      And although Simplifications like the Rule-Of-Nines-Method ([Weidringer, 2002]),
      Lund and Browder ([LundBrowder, 1944]) and others try to compensate for these
      errors, the fact remains that different physicians overestimate the BSA (Body
      Surface Area) by 20% up to 50%, depending on the different experience and
      subjectivity of the approximation process. Nevertheless, different supporting
      mechanisms have been developed to assist the process of burn region transfer so
      that after transferring all burned regions on the virtual human body,
      calculations can be applied in order to evaluate standard indices like the ABSI
      (Abbreviated Burn Severity Index), and Baux ([Baux, 1989]) as well as ICD10
      (International Classification of Diseases) diagnosis encoding. The virtual body
      simulation is based on state-of-the-art 3D computer graphics (OpenGL). Thus a
      simulation system, providing a graphical user interface, allows surgeons to
      transfer a patient's burn injury regions onto an appropriate 3-dimensional model.
      As such, the BurnCase system improves surface determination by calculating region
      surfaces up to a precision of one cm2. This improves the average variation to
      less than 5%, limited by the precision of the surface transfer onto the virtual
      model. The system already allows the transfer of burned regions by using standard
      input devices. For this purpose different reference models of human bodies have
      been created in order to receive appropriate results based on measured physical
      data of different patients. Moreover, an underlying database stores all entered
      case studies so that it is possible to perform comparisons of burn cases and
      animation sequences of the healing process of single wounds or whole bodies. When
      used as centralized burn accident registration service, a huge knowledge base of
      burn diagnoses and consequent medical treatment will emerge. This knowledge base
      will allow medical advices and diagnosis support for any kind of burn accidents,
      and it will consequently improve and support the primary diagnosis process of
      burn accidents. Thus, an enormous reduction of time and costs of medical burn
      treatment will be reached.

PMID- 15455864
TI  - Novel algorithms for polarization imaging resulting in improved quantification of
      retinal blood vessels.
AB  - Novel algorithms of polarization imaging data produce views not visible in the
      images resulting from the instrumentations. These computed images are rapidly
      produced, and reveal clinically relevant features. A virtual reality
      implementation that allows a selection of such views during diagnostic procedures
      or treatment might improve patient management.

PMID- 15455865
TI  - 3D tooth shape from radiographs using thin-plate splines.
AB  - Current methods to produce 3-dimensional tooth root models involve conversion
      from radiographic means (computed tomography) or creation using computer-assisted
      design (CAD) software. The former lacks detail while the second is manually
      fabricated and can bear little resemblance to the original. Thin-plate splines
      have been used in morphometrics to define changes of shape between subjects of
      the same species. Herein, we use thin-plate splines to deform a 3D geometric
      prior model of a tooth to match 2D patient radiographs, producing a "best-fit"
      patient specific 3D geometric polygonal mesh of the tooth.

PMID- 15455866
TI  - The virtual craniofacial patient: 3D jaw modeling and animation.
AB  - In this paper, we present new developments in the area of 3D human jaw modeling
      and animation. CT (Computed Tomography) scans have traditionally been used to
      evaluate patients with dental implants, assess tumors, cysts, fractures and
      surgical procedures. More recently this data has been utilized to generate
      models. Researchers have reported semi-automatic techniques to segment and model
      the human jaw from CT images and manually segment the jaw from MRI images.
      Recently opto-electronic and ultrasonic-based systems (JMA from Zebris) have been
      developed to record mandibular position and movement. In this research project we
      introduce: (1) automatic patient-specific three-dimensional jaw modeling from CT
      data and (2) three-dimensional jaw motion simulation using jaw tracking data from
      the JMA system (Zebris).

PMID- 15455867
TI  - Dynamic MR-mammography in virtual reality.
AB  - In view of an increasing use of breast MRI supplementing X-ray mammography, the
      purpose of this study was the development of a method for fast and efficient
      analysis of dynamic MR image series of the female breast. The image data sets
      were acquired with a saturation-recovery-turbo-FLASH sequence facilitating the
      detection of the kinetics of the contrast agent concentration in the whole breast
      with. In addition, a morphological 3D-FLASH data set was acquired. The dynamic
      image data sets were analyzed by tracer kinetic modeling in order to describe the
      physiological processes underlying the contrast enhancement in mathematical terms
      and thus to enable the estimation of functional tissue specific parameters,
      reflecting the status of microcirculation. To display morphological and
      functional tissue information simultaneously, a multidimensional real-time
      visualization system (using 3D-texture mapping) was developed, which enables a
      practical and intuitive human-computer interface in virtual reality. The
      spatially differentiated representation of the computed functional tissue
      parameters superimposed on the anatomical information offers several
      possibilities: improved discernibility of contrast enhancement; inspection of the
      data volume in 3D-space using the features of rotation and transparency
      variation; localization of lesions in space and thus fast and more natural
      recognition of topological coherencies. In a feasibility study, it could be
      demonstrated that multidimensional visualization of contrast enhancement in
      virtual reality is a practicable idea. Especially, detection and localization of
      multiple breast lesions may be an important application.

PMID- 15455868
TI  - Development of an interactive teaching system based on motion synchrony between
      physical and virtual models.
AB  - In advancing our capabilities in the realm of virtual reality, the development of
      haptic technology has been a rate-limiting factor in producing tactile sensations
      directly onto the human hands. The Living Anatomy Program seeks to obviate the
      need for such technology by designing physical objects based on anatomic
      components that feel realistic to the touch. Furthermore, synchronizing motion
      between physical and related virtual objects infinitely expands visual design
      options and provides a profound level of immersion into content.

PMID- 15455869
TI  - 3D visualization methods to guide surgery for Parkinson's disease.
AB  - In this paper we present 2D and 3D visualization techniques that are part of our
      ongoing effort to improve the accuracy of neurosurgical procedures such as
      'Pallidotomy' and 'Deep Brain Stimulation' (DBS), which are performed to
      alleviate the symptoms of Parkinson's disease. The precise targeting and mapping
      of structures in the Basal Ganglia particularly the internal Globus Pallidus
      (GPi) using a combination of stereotactic frame- registered Magnetic Resonance
      Imaging (MRI) and intraoperative microelectrode recording (IMR) is key to the
      success of these procedures. We have designed a set of software components,
      including a knowledge-based system (KBS), a digital signal processing module and
      a 2D/3D imaging system with automated mapping paradigm, which will work in
      combination to improve upon the standards currently in use. The imaging system
      will be the focus of this publication.

PMID- 15455870
TI  - Realistic Virtual Endoscopy of the ventricle system and haptic-based surgical
      simulator of hydrocefalus treatment.
AB  - New methods and software tools for automatic extraction of the ventricle system
      from magnetic resonance imagery (MRI) data, ventricle part classification, and
      realistic texturing are proposed to support Virtual Endoscopy (VE). Volume- and
      surface-based medical atlases are intensively used as templates in the methods.
      The processed ventricle-related surfaces are then utilized in a haptic-based
      system, which provides a surgeon with several basic functions simulating "virtual
      treatment" of hydrocephalus.

PMID- 15455871
TI  - Cybercare: virtual reality technologies for homeland defense.

PMID- 15455872
TI  - Trauma team training in a distributed virtual emergency room.
AB  - A distributed simulation environment for training and evaluation of medical
      trauma teams is presented. Connected through the Internet, the geographically
      remote team members can communicate and interact using the clinically realistic
      environment provided by the MATADOR simulator. The scenario demonstrates an
      injured person's arrival at the hospital, and the diagnostic and therapeutic
      challenges that must be met in order to stabilize the virtual patient.
      Experiences from a field trial indicate that the simulator is useful both for
      professionals and medical students.

PMID- 15455873
TI  - Comparing a simplified FEM approach with the mass-spring model for surgery
      simulation.
AB  - Virtual reality based surgical simulators offer a very elegant approach to
      enhancing traditional training in endoscopic surgery. In this context a realistic
      soft tissue model is of central importance. The most accurate procedures for
      modeling elastic deformations of tissue use the Finite Element Method (FEM) to
      solve the governing mechanical equations. An alternative are mass-spring models
      which are a crude approximation of the real physical behavior. The main reason
      given when using the mass-spring approach is the computational complexity of FEM.
      In this study we show that an optimized linear FEM model requires computation
      time similar to the mass-spring approach, while giving better results.

PMID- 15455874
TI  - A robotic surgery system (da Vinci) with image guided function--system
      architecture and cholecystectomy application.
AB  - We have developed a data fusion system for the robotics surgery system "da
      Vinci". The data fusion system is composed of an optical 3D location sensor and a
      digital video processing system. The 3D location sensor is attached to the da
      Vinci's laparoscope and measures its location and direction. The digital video
      processing system captures the laparoscope's view and superimposes 3D patient's
      organ models onto the captured view in real-time. We applied the system to "da
      Vinci" and examined this system during a cholecystectomy. In this experiment, the
      surgeon was able to observe the inner conditions of the organs with a stereo
      view.

PMID- 15455875
TI  - Real-time 3D deformation imaging of abdominal organs in laparoscopy.
AB  - In laparoscopic surgery, surgeons encounter particular difficulties during the
      course of the operation. Due to the restricted view from the endoscope and the
      limited degree of freedom using forceps, surgeons find their movements impeded.
      It would be necessary to develop a support system to provide surgeons with
      improved laparoscopic vision. If real-time visualization of the abdominal anatomy
      is possible, it will be useful for accurate procedure and quantitative
      evaluation. In this paper, The laser-scan endoscope system acquires and
      visualizes the shape and texture of the area of interest in a flash of time.
      Results of in-vivo experiments on the liver of a pig verify the effectiveness of
      the proposed system.

PMID- 15455876
TI  - Metrics and motion analysis for assessment of surgical skills.
AB  - Pressure has grown over the past decade to provide more rigorous and standardized
      testing of surgical trainees at both higher and lower levels. VR technologies
      appear to offer a solution but the cost of equipment and realism of the interface
      present major research challenges. The central requirement of simulation remains
      assessment, however, and the present study examines this issue within the context
      of surgical suturing skills. By tracking users during suturing tasks, we argue
      that errors in technique can be analysed by the examination of standard pattern
      spaces.

PMID- 15455877
TI  - Lessons learned in modeling virtual pediatric patients.
AB  - In two applications the authors are developing virtual pediatric characters for
      training and assessment. One application, a virtual pediatric standardized
      patient, is intended for medical school students rotating through pediatrics to
      train and assess their basic communications and procedural skills while
      interacting with kids. The other application presents at-risk teenagers with
      vignettes to assess risky behavior and impulsivity. Both applications rely on
      existing responsive virtual human technology. The authors are engaged in
      preliminary clinical trials for the work described in this paper.

PMID- 15455878
TI  - Surface transparency makes stereo overlays unpredictable: the implications for
      augmented reality.
AB  - The principle of using stereoscopic displays is to present the viewer with an
      accurate perception of 3D space. Stereopsis is a powerful binocular cue that will
      supplement any monocular information in the scene. Our work with an optical
      augmented reality system has highlighted one scenario where an accurate sense of
      depth cannot be easily achieved from stereoscopic images. In our augmented
      reality system we use stereo images of anatomical structures overlaid on the
      patient for surgical guidance. It is essential that the surgeon can accurately
      localize the images during surgery. When the stereo images are presented behind
      the transparent physical surface the perception of the depth of the images can
      become unstable and ambiguous, despite good system calibration, registration and
      tracking. This paper reviews possible reasons for the failure in accurate depth
      perception and presents some ideas on how this might be corrected for in an
      optical augmented reality

PMID- 15455879
TI  - Independent testing of soft tissue visco-elasticity using indentation and rotary
      shear deformations.
AB  - Numerous techniques exist to measure the mechanical properties of soft tissues in
      vivo, such as mechanical stretching, indentation or shearing, as well as
      elastographic methods employing ultrasound or other imaging modes. Many groups
      have reported properties which do not necessarily correspond with each other due
      to differences in choice of technique, tissue model or other variations. This
      work deliberately makes use of the two independent modes of indentation and
      rotary shear, on the same material samples, employing similar modeling
      approximations, to attempt to determine the common, underlying material
      properties. This paper introduces the ROSA-2 rotary shear instrument, and
      presents its mechanical characteristics, as well as presenting validation
      experiments that were performed to verify non-slip contact with tissue.
      Measurements made with it are compared with those acquired with the TeMPeST l-D
      indentation instrument. Initial testing showed reasonably agreement when testing
      silicone gel samples, over a restricted range of frequencies. When testing bovine
      liver samples in vitro and porcine liver in vivo, significant discrepancies were
      found. The potential sources of these differences will be discussed, as will
      directions for ongoing work.

PMID- 15455880
TI  - A haptic sensor-actor-system based on ultrasound elastography and
      electrorheological fluids for virtual reality applications in medicine.
AB  - Mechanical properties of biological tissue represent important diagnostic
      information and are of histological relevance (hard lesions, "nodes" in organs:
      tumors; calcifications in vessels: arteriosclerosis). The problem is, that such
      information is usually obtained by digital palpation only, which is limited with
      respect to sensitivity. It requires intuitive assessment and does not allow
      quantitative documentation. A suitable sensor is required for quantitative
      detection of mechanical tissue properties. On the other hand, there is also some
      need for a realistic mechanical display of those tissue properties. Suitable
      actuator arrays with high spatial resolution and real-time capabilities are
      required operating in a haptic sensor actuator system with different
      applications. The sensor system uses real time ultrasonic elastography whereas
      the tactile actuator is based on electrorheological fluids. Due to their small
      size the actuator array elements have to be manufactured by micro-mechanical
      production methods. In order to supply the actuator elements with individual high
      voltages a sophisticated switching and control concept have been designed. This
      haptic system has the potential of inducing real time substantial forces, using a
      compact lightweight mechanism which can be applied to numerous areas including
      intraoperative navigation, telemedicine, teaching, space and telecommunication.

PMID- 15455881
TI  - An Augmented Reality system for MRI-guided needle biopsies.
AB  - A navigation system can increase the speed and accuracy of MR guided
      interventions that make use of scanners with high-field closed magnets. We report
      on first needle placement experiments performed with an Augmented Reality (AR)
      navigation system. AR visualization provides very intuitive guidance, resulting
      in a faster procedure. The accuracy of the needle placement depends on the
      registration accuracy of the system. In the present trials, the needle was placed
      as good as 1mm close to the target center, however in a small number of cases
      substantially larger errors occurred and were most likely caused by needle
      bending.

PMID- 15455882
TI  - Physically based hybrid approach in real time surgical simulation with force
      feedback.
AB  - This paper describes a novel hybrid-modeling paradigm for the simulation of
      surgical tool-soft tissue interactions in real time medical simulations using
      force feedback. A local point collocation-based method of finite spheres is
      coupled with a global boundary element technique to capture local features of the
      interaction (e.g., nonlinearities of the soft tissue) without sacrificing global
      accuracy. The technique is demonstrated using realistic examples.

PMID- 15455883
TI  - Virtual simulated patients for bioterrorism preparedness training.

PMID- 15455884
TI  - Development of a new three-dimensional endoscopic ultrasound system through
      endoscope shape monitoring.
AB  - We have developed a new three-dimensional (3D) endoscopic ultrasound system (EUS)
      with convex scanning echoendoscope to diagnose and navigate for endoscopic
      puncture using the 3D image. To detect the position of the probe and to monitor
      the shape of the scope inside the body, we use a fiber optic tracking system
      which is shaped like a ribbon (Shapetape, Measurand Inc.). The fiber optic
      tracking system could measure bend and twist at each position of the ribbon. The
      position of the tip of the echoendoscope is allotted to a 2D image, and the
      system can reconstruct and visualize a 3D image in real-time. We have reported
      results of our experimental studies and animal studies.

PMID- 15455885
TI  - Automatic segmentation of the liver for preoperative planning of resections.
AB  - This work presents first quantitative results of a method for automatic liver
      segmentation from CT data. It is based on a 3D deformable model approach using a
      priori statistical information about the shape of the liver gained from a
      training set. The model is adapted to the data in an iterative process by
      analysis of the grey value profiles along its surface normals after nonlinear
      diffusion filtering. Leave-one-out experiments over 26 CT data sets reveal an
      accuracy of 2.4 mm with respect to the manual segmentation.

PMID- 15455886
TI  - Training brain retraction in a virtual reality environment.
AB  - A computer based virtual reality system is presented allowing the user to train
      skills related to brain retraction. The system is designed and the core training
      system implemented and tested. The initial test shows promising results.

PMID- 15455887
TI  - The wireless and paperless E.R.: an economical and ergonomic approach.
AB  - An approach is presented to achieve a wireless and paperless recording of
      acquired patient data and other administrative tasks such as prescription of x
      rays and laboratory tests in an emergency room in an ergonomic and economic way
      by means of the use of bar code technology, which is linked to the existing
      hospital informatics systems.

PMID- 15455888
TI  - Eye trackers in a virtual laparoscopic training environment.
AB  - Virtual laparoscopic training systems have been shown to differentiate between
      the skills of experienced and novice laparoscopic surgeons. Measures such as
      total number of errors and completion time are used to assess skill, but these
      metrics do not give much insight into the processes behind skilled behavior in
      simulated laparoscopic tasks. The eye gaze of 2 groups of subjects, one
      experienced with laparoscopic surgery, and the other with no experience, was
      recorded while they performed an aiming task in a virtual laparoscopic trainer.
      The experienced subject committed much lower number of errors than the novices.
      Initial analysis of the eye data showed that the novice group tended to gaze on
      the tool they are controlling more often than the experienced subject.

PMID- 15455889
TI  - A haptic needle manipulation simulator for Chinese acupuncture.
AB  - Chinese acupuncture is a traditional medical treatment in Chinese history. Recent
      evidence shows that this treatment is effective. However, acupuncture students
      can only practice on either real patients or mannequin. In this project, we
      propose a virtual reality training system for acupuncture. The system not just
      provides 3D stereo display, but also realistic haptic feedback in real-time.
      Since acupuncture usually involves thrust-and-lift needle motion, we also propose
      a bi-directional haptic model to tailor this application. Our results show that
      the novel haptic model confirms with practitioners' tactile experience.

PMID- 15455890
TI  - Real-time web-based telerehabilitation monitoring.
AB  - Distance monitoring of rehabilitation exercises has been primarily conducted
      using two-way video conferencing. This paper presents a real-time web-based
      monitoring system that greatly enhances the capability of the clinician to direct
      rehabilitation therapies.

PMID- 15455891
TI  - Development and evaluation of a simulator of invasive procedures in pediatric
      bone marrow transplant.
AB  - In the past we proposed the development of a bone marrow harvest simulator to
      support the learning of this procedure. This work presents some aspects of this
      development and shows the results and analysis of the simulator after its first
      evaluation.

PMID- 15455892
TI  - Validation of medical modeling & simulation training devices and systems.
AB  - For almost a decade, research has been conducted in many areas of science to
      develop medical simulation training devices and even comprehensive training
      systems. To propel the field, the Telemedicine and Advanced Technology Research
      Center (TATRC), an agency of the United States Army Medical Research Materiel
      Command (USAMRMC), has been managing a portfolio of research projects in the area
      of Medical Modeling and Simulation (MM&S) since 1999. Significant progress has
      made to identify and harness enabling technologies. Generally, these developments
      can be categorized in four areas: (1) PC-based interactive multimedia, (2)
      Digitally Enhanced Mannequins, (3) Virtual Workbench, or "part-task", simulators,
      and (4) Total Immersion Virtual Reality (TIVR). Many medical simulation-training
      systems have shown great potential to improve medical training, but the potential
      shown has been based largely on anecdotal feedback from informal user studies.
      Formal assessment is needed to determine the degree to which simulator(s) train
      medical skills and the degree to which skills learned on a simulator transfer to
      the practice of care. A robust methodology is required as a basis for these
      assessments. Several scientific workshops sponsored in 2001 focused on algorithm
      and metrics development in support of surgical simulation. Also in 2001, TATRC
      chartered a Simulation Working Group (SWG) to develop a robust methodology upon
      which to base an assessment of the effectiveness of simulation training devices
      and systems. After the terrorist attacks of September 11, 2001, attention was
      redirected for a period, and progress was delayed. In the summer of 2002, TATRC
      chartered a follow-on group called the Validation, Metrics and Simulation (VMAS)
      Committee. The poster will highlight and summarize the development of the
      methodology and identify validation studies to be conducted (supported by various
      funding sources and research programs). The interaction between TATRC and the
      National Capital Area Medical Simulation Center (NCAMSC) will be noted.

PMID- 15455893
TI  - Inclusion of 3-D computed tomography rendering and immersive VR in a third year
      medical student surgery curriculum.
AB  - Computed tomography (CT) scans are frequently used for preoperative evaluation of
      patients undergoing complex surgery and are therefore commonly encountered by
      medical students on their surgical rotations. Interpretation of these CT scan
      images is therefore an integral component of all medical students' surgical
      rotations. Additionally, advanced rendering available from modem scanners and
      registration of multimodal or serial scans require the student to understand how
      volumetric anatomy relates to cross-sectional anatomy. The utility of three
      dimensional (3-D) models for conveying surgical anatomy has been demonstrated.
      Immersive 3-D VR overcomes many of the conceptual limitations encountered when
      conveying or teaching 3-D relationships via 2-D images traditionally produced by
      these scans. We are currently using augmented reality as a teaching tool and have
      incorporated 3-D immersive environments in the third year medical student Surgery
      rotation. Initial results suggest that this is an effective tool for teaching
      third year medical students. 3-D CT rendering and immersive VR provide an
      effective process for utilizing CT datasets to teach surgical anatomy to medical
      students.

PMID- 15455894
TI  - A surgical simulator for cleft lip planning and repair.
AB  - The objective of this project was to develop a computer-based surgical simulation
      system for cleft lip planning and repair. This system allows the user to interact
      with a virtual patient to perform the traditional steps of cleft-lip repair. The
      system interfaces to force-feedback (haptic) devices to track the user's motion
      and provide feedback during the procedure, while performing real-time soft-tissue
      simulation. An eleven-day old unilateral cleft-lip and palate patient was
      previously CT scanned for ancillary diagnostic purposes using standard imaging
      protocols and 1mm slices. High-resolution 3D meshes were automatically generated
      from this data using the ROVE software created in our lab. The resulting 3D
      meshes of bone and soft-tissue were instilled with physical properties of soft
      tissues for purposes of simulation. Once these preprocessing steps were
      completed, the patient's bone and soft-tissue data are presented on the computer
      screen in stereo and the user can freely view, rotate, and otherwise interact
      with the patient's data in real-time. The user is prompted to select anatomical
      landmarks on the patient data for preoperative planning purposes, then their
      locations are compared against that of a "gold standard" and a score, derived
      from their deviation from that standard and time required, is generated. The user
      can then move a haptic stylus and guide the motion of the virtual cutting tool.
      The soft tissues can thus be incised using this virtual cutting tool, moved using
      virtual forceps, and fused in order to perform any of the major procedures for
      cleft-lip repair. Real-time soft tissue deformation of the mesh realistically
      simulates normal tissues and haptic-rate (>1kHz) force-feedback is provided. The
      surgical result of the procedure can then be immediately visualized and the
      entire training process can be repeated at will. A short evaluation study was
      also performed. Two groups (nonmedical and plastic surgery residents) of six
      people each performed the anatomical marking task of the simulator four times.
      Results showed that the plastic surgery residents scored consistently better than
      the people without medical background. Every person's score increased with
      practice, and the length of time needed to complete the eleven markings
      decreased. The data was compiled and showed which specific markers consistently
      took users the longest to identify as well as which locations were hardest to
      accurately mark. Our findings suggest that the simulator is a valuable training
      tool, giving residents a way to practice anatomical identification for cleft lip
      surgery without the risks associated with training on a live patient. Educators
      can also use the simulator to examine which markers are consistently problematic,
      and modify their training to address these needs.

PMID- 15455895
TI  - Virtual instruments: a generalized implementation.
AB  - The proliferation of surgical simulators would be increased if a common framework
      and set of virtual instruments existed for use by the application developer. We
      describe such a framework consisting of a powerful abstraction of a user
      interaction device, a functional taxonomy of surgical instruments, and a method
      for linking these components together. A series of example virtual instruments is
      also provided.

PMID- 15455896
TI  - A part-task approach to haptic knee arthroscopy training.
AB  - This paper describes the research behind a part-task approach to both the
      development of, and the training offered, by a virtual reality simulator for knee
      arthroscopy. An ethnographic approach has been taken to examine the nature of
      task performance and the current training of the arthroscopic diagnosis of the
      knee. This Human Factors research is used to support the development of WISHKATS.
      The design addresses the challenge of technically producing haptic feedback for a
      knee surgery simulator whilst offering sufficient fidelity to train the necessary
      skills and conform to traditional surgical training.

PMID- 15455897
TI  - Validation of a web-based training tool for lumbar puncture.
AB  - WebSET is an Internet based educational tool that can be used on any standard
      personal computer. It has been developed by a European collaboration and
      integrates high quality courseware, self-assessment exercises, video clips and VR
      simulation. This pilot study was carried out to validate the lumbar puncture (LP)
      module in training. Subjects who had never performed an LP participated in the
      study. The subjects were randomized into 2 groups: 1) underwent training and 2)
      control group. Both groups performed a pre-test and post-test LP on a synthetic
      mannequin. There was a significant improvement in the training group in terms of
      performance assessment as compared to the control group. This study showed that
      there was a significant improvement in the performance of the procedure and in
      procedural knowledge after training with WebSET.

PMID- 15455898
TI  - The operating room of the future: white paper summation.
AB  - On November 8 and 9, 2001, leading experts in patient safety, medical
      informatics, advanced surgical devices, telesurgery, and surgical facilities met
      to formulate strategic directions for the "OR of the Future" in both military and
      civilian healthcare. The meeting was co-hosted by the Telemedicine and Advanced
      Technology Research Center (TATRC) part of the U.S. Army Medical Research and
      Materiel Command at Fort Detrick, and the University of Maryland Medical Center.
      Researchers, surgeons, and experts in the field of operating room (OR) technology
      addressed the current state of research and technological developments. Experts
      in (1) patient safety, (2) medical informatics, (3) advanced surgical devices,
      (4) telesurgery, and (5) surgical facilities met in focused work groups to
      develop a proposed research agenda for each content area. Afterwards, each
      focused group agreed to develop a 'White Paper' on each specific area, addressing
      the current and future prospectus. In addition, they attempted to provide a
      recommended research roadmap for the 'OR of the Future.'

PMID- 15455899
TI  - Real-time PC based X-ray simulation for interventional radiology training.
AB  - The ability to simulate realistic fluoroscopic images in real-time is a key
      aspect of any interventional radiology training system. In this paper, we propose
      a method for rendering X-ray images in real-time on a PC with consumer level
      graphics hardware, while improving the quality of the images. Although volume
      rendering techniques form the basis of our algorithm, we studied the
      characteristics of actual X-ray images to develop a method that can provide a new
      level of realism. In addition, the integration of the various levels of
      information contained in a CT scan in the rendering pipeline can be exploited to
      produce even more realistic, patient-specific X-ray or fluoroscopic images.
      Although the results presented here are preliminary, the performance of multi
      texturing and multi-stage rasterization features available on recent low-cost
      graphics hardware already allows us to render X-ray images at about 30 frames per
      second.

PMID- 15455900
TI  - Evaluation of a novel electronic fetal monitor simulator.
AB  - The purpose of this study was to evaluate the content validity and construct
      validity of a novel electronic fetal monitor (EFM) simulator. Fourteen residents
      in Gynecology and Obstetrics (OB/GYN) and 7 medical students in their OB/GYN
      clerkship interpreted 10 fetal heart rate (FHR) tracings and 4 clinical scenarios
      generated by the EFM simulator. Their responses were scored by experts in
      maternal-fetal medicine. Construct validity was determined by comparing subjects'
      scores to their level of experience. Subjects assessed content validity of the
      EFM simulator by rating the realism of its various elements on a 4-point Likert
      scale. Residents achieved statistically significant higher mean scores in the
      description of FHR tracings generated by the simulator than medical students and
      statistically significant higher mean scores in the correct interpretation of and
      interventions in 2 of 4 clinical scenarios. Two-thirds of the residents rated the
      simulator-generated FHR tracings and clinical scenarios as "real" or "very real."
      The EFM simulator exhibited both content and construct validity, supporting its
      use in an educational setting.

PMID- 15455901
TI  - Virtual reality therapy in aid of senior citizens' psychological disorders.
AB  - The treatment for senior citizens suffering from psychological disorders seems to
      be different from therapeutic procedures used for other populations. This pilot
      study is the first known in-depth case study of the effectiveness of virtual
      reality therapy (VRT) as a treatment for senior citizens. The fear of flying
      treatment was chosen for this study. The subject of the study was a 62-year-old
      married female, whose anxiety and avoidance behavior was interfering with her
      normal activities. For treatment, she was placed in the cabin of a virtual
      commercial aircraft environment accompanied by a virtual therapist. After a few
      sessions in which she spent time in a virtual airport scene, she spent four
      sessions in which she was flown over a simulated city. While under the virtual
      reality treatment, the subject experienced a number of physical and emotional
      anxiety-related symptoms. These symptoms included sweaty palms, loss of balance,
      weakness in the knees, etc. In this study, the virtual reality treatment caused a
      significant reduction in the anxiety symptoms in the subject and enhanced her
      ability to face phobic situations in the real world. Since termination of the
      treatment, she has taken several flights to professional conferences and reported
      feeling more comfortable and has fewer symptoms than those experienced prior to
      the VRT treatment.

PMID- 15455902
TI  - Use of an augmented reality display of patient monitoring data to enhance
      anesthesiologists' response to abnormal clinical events.
AB  - One obstacle to safety in the operating room is anesthesiologist distraction
      having to shift attention back and forth from the patient to a vital sign monitor
      while performing either routine or emergency procedures. The purpose of this
      study was to measure the decrease in anesthesiologist distraction made possible
      by using a head-worn, see-through personal display (HWD) using retinal scanning
      technology. With the head-up display, they were able to focus their attention
      exclusively on the patient and the task at hand. The Nomad reduced the number of
      times the anesthesiologist had to shift their attention by a more than a third
      (17 times versus 58 times). This allowed them to spend more time focused on the
      patient.

PMID- 15455903
TI  - 4-dimensional computer-based motion simulation after Total Hip Arthroplasty.
AB  - This paper represents a novel 4-dimensional(4D) computer-based motion simulation
      system for patients having had Total Hip Arthroplasty(THA). By constructing the
      skeletal model of the patient's lower extremity and measuring daily motions, we
      simulated the movement of the inner structures including the skeleton and the
      artificial joint. This system visually represents not only the 3-dimensional(3D)
      anatomical structure but also the 4-dimensional dynamic functions that represent
      the time sequential transitions of the position of each component. Clinicians can
      get detailed information of the movement of the hip joint quantitatively and give
      precise guidance for the patients with regard to postoperative daily motions. The
      measurement error was evaluated by performing experiments using OpenMRI and the
      results indicated sufficient accuracy of this system. We believe that this system
      enables clinicians to reveal the causes of complications after THA and encourages
      the development of new surgical techniques, materials. and designs of prostheses.

PMID- 15455904
TI  - Stereo visualization of 3D trabecular bone structures produced by bone
      remodelling simulation.
AB  - Adult human bone is constantly being renewed by a process known as remodelling.
      For cancellous bone this renewal process occurs at the interface between bone and
      marrow where bone is depleted by osteoclasts and rebuilt by osteoblasts. This
      remodelling process allows bone to repair itself. Software simulators for bone
      remodelling provide insight into the bone remodelling process; they allow
      investigation into bone form and structural properties, and they also allow the
      emulation of bone diseases and possible treatments for these diseases over long
      periods of time. BONESIM is a software that simulates bone remodelling in terms
      of Basic Multi-cellular Units (BMUs). 3D visualization of trabecular bone and its
      attributes is an essential tool in understanding this remodelling process for
      cancellous bone. It enables the bone researcher to quickly understand the dynamic
      behaviour of remodelling, the resulting geometry of the bone structure and it
      allows alternative remodelling scenarios to be compared. This paper presents the
      volume visualization technique that has been developed to provide this
      visualization tool.

PMID- 15455905
TI  - The augmented-feedback rehabilitation technique facilitates the arm motor
      recovery in patients after a recent stroke.
AB  - Previous studies have shown that the motor training in a virtual-environment with
      the augmented feedback promotes motor learning in normal subjects and in long
      term post-stroke patients. We evaluated whether this approach could be useful
      also for treating patients with arm motor deficits due to a recent stroke. Twenty
      four patients were included in the study within 3 months from an ischemic stroke
      in the territory of the middle cerebral artery. Twelve subjects received virtual
      environment-training (VET) therapy for the arm, and twelve patients received an
      equal amount of a conventional rehabilitation therapy focused to the upper limb.
      Before and after therapy, the autonomy of daily living activities were assessed
      with the Functional Independence Measure and the degree of motor impairment was
      measured with the Fugl-Meyer scale for the upper extremity. For both groups the
      therapy lasted from 5 to 7 weeks, 1 hour daily for five days a week. The VET
      therapy group showed 20,2% and 12,4% improvements in the Fugl-Meyer and the
      Functional Independence Measure scale mean scores respectively. In a comparable
      way, the conventional therapy determined significant, but smaller scores
      improvements: 11,3% and 9,1%, respectively. These data indicate that the recovery
      of arm motor function in patients after a recent stroke is promoted by an
      augmented feedback strategy applied through a virtual-environment.

PMID- 15455906
TI  - Interrogative visualization: embedding deformation and Constructive Solid
      Geometry into volume visualization.
AB  - Existing volume visualization algorithms lack sophisticated volumetric modeling
      capabilities to represent, construct and manipulate objects of interest within a
      volumetric dataset. Integrating manipulations such as non-linear deformations and
      constructions similar to those in solid modeling into the visualization process
      would have significant value in surgical planning and simulation. Interrogative
      visualization--the ability to extract, enumerate, deform and track objects of
      interest is also crucial in other visualization tasks. The conventional approach
      to visualize the volume deformation and construction process is to construct an
      intermediate volume for each step of manipulation. This is prohibitively time
      consuming and costly. This paper presents an approach to overcome this
      constraint. We model the target capture space as octrees. The target octree is
      adaptively subdivided to efficiently balance the complexity of deformation and
      visualization. The source volumetric data can either be in octree or conventional
      3D array format. Deformations are specified by landmark displacements, and in
      between deformation is filled in by scattered data interpolation. Volumetric
      modeling is supported by a Constructive Solid Geometry (CSG) structure. Spatial
      Coherency is exploited in the view-dependent node traversal and projection of
      individual octree nodes.

PMID- 15455907
TI  - Visible Human 2.0--the next generation.
AB  - The National Library of Medicine has initiated the development of new anatomical
      methods and techniques for the acquisition of higher resolution data sets, aiming
      to address the anatomical artifacts encountered in the development of the Visible
      Human Male and Female and to insure enhanced detection of structures, providing
      data in greater depth and breadth. Given this framework, we acquired a complete
      data set of the head and neck. CT and MR scans were also obtained with
      registration hardware inserted prior to imaging. The arterial and venous systems
      were injected with colorized araldite-F. After freezing, axial cryosectioning and
      digital photography at 147 microns/voxel resolution was performed. Two slabs of
      the specimen were acquired with a special tissue harvesting technique. The
      resulting tissue slices of the whole specimen were stained for different tissue
      types. The resulting histological material was then scanned at a 60x
      magnification using the Virtual Slice technology at 2 microns/pixel resolution
      (each slide approximately 75,000 x 100,000 pixels). In this data set, for the
      first time anatomy is presented as a continuum from a radiologic granularity of 1
      mm/voxel, to a macroscopic resolution of .147 mm/voxel, to microscopic resolution
      of 2 microns/pixel. The hiatus between gross anatomy and histology has been
      assumed insurmountable, and until the present time this gap was bridged by
      extrapolating findings on minute samples. The availability of anatomical data
      with the fidelity presented will render it possible to perform a seamless study
      of whole organs at a cellular level and provide a testbed for the validation of
      histological estimation techniques. A future complete Visible Human created from
      data acquired at a cellular resolution, aside from its daunting size, will open
      new possibilities in multiple directions in medical research and simulation.

PMID- 15455908
TI  - Force-torque input enhances medical VR applications.
AB  - Force-torque measuring input devices can significantly enhance the performance of
      classical simulation environments that are, for example, based on pure passive
      phantoms. Such devices allow not only the determination of force/torque amplitude
      and direction but also the contact point, where a torque-free force is applied to
      the phantom. The force/torque information can be displayed visually or
      acoustically, drive a realistic graphical animation environment or it can be
      saved and compared with a haptic library comprising the force/torque history of
      any medical specialist.

PMID- 15455909
TI  - The JoyntStick: a new force-input-device for a multi-modal desktop simulator.
AB  - This paper presents a new force-torque input device that can be used to navigate
      within any kind of anatomical atlas. As an example, we demonstrate how it can be
      used to drive a virtual knee joint. The device is comprised by a realistic
      phantom shank that is attached to a self-made high-sensitive force-torque sensor.
      It records forces and moments in six degrees-of-freedom and feeds them into a
      biomechanical model of the knee. Resulting joint movements and sounds are
      displayed by a visual and acoustic display, respectively. The entire multi-modal
      simulation environment can provide a better understanding of joint anatomy, e.g.
      for the education of medical students. Furthermore, it can be a practical tool
      for resident orthopaedic physicians in order to enhance the consultation,
      clarification, and treatment planning together with the patient.

PMID- 15455910
TI  - Development of a training tool for endotracheal intubation: distributed augmented
      reality.
AB  - The authors introduce a tool referred to as the Ultimate Intubation Head (UIH) to
      train medical practitioners' hand-eye coordination in performing endotracheal
      intubation with the help of augmented reality methods. In this paper we describe
      the integration of a deployable UIH and present methods for augmented reality
      registration of real and virtual anatomical models. The assessment of the 52
      degrees field of view optics of the custom-designed and built head-mounted
      display is less than 1.5 arc minutes in the amount of blur and astigmatism, the
      two limiting optical aberrations. Distortion is less than 2.5%. Preliminary
      results of the registration of a physical phantom mandible on its virtual
      counterpart yields less than 3mm rms. in registration. Finally we describe an
      approach to distributed visualization where a given training procedure may be
      visualized and shared at various remote locations. Basic assessments of delays
      within two scenarios of data distribution were conducted and reported.

PMID- 15455911
TI  - Minimally invasive surgery task decomposition--etymology of endoscopic suturing.
AB  - The analogy between Minimally Invasive Surgery (MIS) and the human language
      inspires the decomposition of a surgical task into its primary elements. The
      frequency of different elements or words" and their sequential associations or
      "grammar" both hold critical information about the process and outcome of the
      procedure. Modeling these sequential element expressions using a multi finite
      states model (Markov model) reveals the grammatical structure of the surgical
      task and is utilized as one of the key steps in objectively assessing surgical
      performance. The experimental protocol included 30 surgeons at different levels
      of training (5xR1,R2,R3,R4,R5, and experts) performing Laparoscopic suturing on
      an animal model (pig). The kinematics and dynamics of left and right endoscopic
      tools along with the visual view of the surgical scene were acquired by the Blue
      DRAGON system. The methodology of decomposing the surgical task is based on a
      fully connected, finite-states (30 states) Markov model (MM) where the left and
      right hands are represented by 15 states each. In addition to the MM objective
      analysis, a scoring protocol was used by an expert surgeon to subjectively assess
      the subjects' technical performance. An objective learning curve was defined
      based on measuring quantitative statistical distance (similarity) between MM of
      experts and MM of residents at different levels of training. The objective
      learning curve (e.g. statistical distance between MM) was similar to that of the
      subjective performance analysis. The MM proved to be a powerful and compact
      mathematical model for decomposing a complex task such as laparoscopic suturing.
      Systems like surgical robots or virtual reality simulators that inherently
      measure the kinematics and dynamics of the surgical tool may benefit from
      inclusion of the proposed methodology for analysis of efficacy and objective
      evaluation of surgical skills during training.

PMID- 15455912
TI  - Virtual Visit: improving communication for those who need it most.
AB  - We are developing a videoconferencing system designed specifically to cater to
      the needs of the elderly and their distant friends and family. Focus group
      research has led to the incorporation of several key features that enhance the
      usability of the system. Audio and video transmission quality are optimized by
      separation, using the proven and familiar capability of analog phone for voice
      and the slightly less reliable, but faster data transmission of broadband
      Internet for video. A simple and intuitive user interface was designed based on
      the familiar steps of an actual household visit. The graphical interface is
      presented on the user's conventional television receiver and controlled by a
      simple seven-button remote control with integrated wireless microphone, which
      provides high quality audio pickup. The system can be remotely activated by a
      wearable wireless alarm button or by visitors with passkey privileges. A
      functional prototype has been developed and is currently undergoing field
      testing. Preliminary response has been very encouraging. Future plans include
      extended focus group research, collaboration to integrate improved video
      transmission schemes, and in-home testing by seniors to gauge long-term user
      response.

PMID- 15455913
TI  - Evaluation of INPRES--Intraoperative Presentation of surgical planning and
      simulation results.
AB  - In this paper we present fundamental results of the first evaluation of INPRES in
      a laboratory environment. While the system itself--an HMD-based approach for
      intraoperative augmented reality in head and neck surgery--has been described
      elsewhere several times, this paper will focus on methods and outcome of recently
      accomplished test procedures.

PMID- 15455914
TI  - Medarpa--a medical augmented reality system for minimal-invasive interventions.
AB  - Minimal-invasive operation techniques have become more important and well
      accepted in the recent years. While offering obvious advantages for the patient,
      these techniques confront the surgeon with a restricted view of the region of
      intervention. This paper presents a novel approach for Computer-Aided Surgery
      (CAS), applying Augmented Reality (AR) techniques together with a novel AR
      Window. As the main objective, the research project Medarpa not only focuses on
      the application of AR techniques in a medical scenario, but also addresses their
      future application in real medical scenarios inside the operating room.

PMID- 15455915
TI  - Four-dimensional analysis of mandibular movements with optical position measuring
      and real-time imaging.
AB  - Mandibular movement findings have not always been useful in clinical, even though
      measuring techniques have improved. This is because there is no method to
      evaluate condylar movement including the position of the temporal bone. In this
      study, we have attempted to apply 3-dimensional imaging to mandibular movement
      data, and have developed a 4-demensional analysis system representing mandibular
      movements. In this system, the mandibular movement can be observed in real-time
      by using the CT dataset from a volunteer. As a result the relationship between
      the mandibular movement and the anatomic structures becomes clear.

PMID- 15455916
TI  - Wireless virtual instrument measurement of surgeons' physical and mental
      workloads for robotic versus manual minimally invasive surgery.
AB  - The human-technology interface in traditional minimally invasive surgery (MIS) is
      difficult for the surgeon. Efforts to improve this interface include the use of
      robotic surgery systems. Ergonomics studies are required to help understand and
      improve the MIS user interface. We have developed a tetherless virtual instrument
      (VI) ergonomics workstation for measuring the physical workloads and stress
      levels of surgeons performing MIS. The workstation records physiological measures
      of workload and stress and audio and multiple channels of video. The workstation
      frees up the subject so that studies can be performed in complex and realistic
      settings, including the operating room. We illustrate the use of the tetherless
      ergonomics workstation in a study to compare performance and workload for manual
      and robotically-assisted MIS. The surgeon volunteers were experienced with manual
      MIS but had no previous experience with the robotic system. The study results
      showed that the robotic system reduced the workload and stress levels for these
      subjects but somewhat degraded their performance. Additional studies are needed
      to determine the relative effects on performance of user inexperience and the
      robotic interface.

PMID- 15455917
TI  - Stereo imagery from the UNC augmented reality system for breast biopsy guidance.
AB  - This paper shows a number of stereoscopic images depicting the UNC augmented
      reality guidance system for medical visualization in operation.

PMID- 15455918
TI  - Facilitating real-time volume interaction.
AB  - We report on efforts to provide high-level intuitive tools that exploit commodity
      based computing to facilitate real-time and distributed interactions with
      volumetric data. These efforts include an open source volume-rendering library, a
      portable volume visualization application framework, and parallel volume
      rendering exploiting commodity-based hardware. We present our design and
      implementations, as well as examples of some of the various groups currently
      utilizing these tools, and discuss the tradeoffs of our developments versus
      existing techniques.

PMID- 15455919
TI  - CELTS: a clinically-based Computer Enhanced Laparoscopic Training System.

PMID- 15455920
TI  - Simulation of a preperitoneal mesh in laparoscopic herniorrhaphy.
AB  - During a laparoscopic hernia surgery, a preperitoneal mesh is tacked or stapled
      to the defect on the inside in order to close the fissure created by the hernia.
      Here we have proposed and implemented a novel technique for simulating the
      movement and stapling of the mesh for use in a virtual reality based laparoscopic
      trainer. The use of particle based system and Mass-Spring model in simulating the
      movement of the mesh is also discussed.

PMID- 15455921
TI  - Development of Dynamic Spatial Video Camera (DSVC) for 4D observation, analysis
      and modeling of human body locomotion.
AB  - We have developed an imaging system for free and quantitative observation of
      human locomotion in a time-spatial domain by way of real time imaging. The system
      is equipped with 60 computer controlled video cameras to film human locomotion
      from all angles simultaneously. Images are installed into the main graphic
      workstation and translated into a 2D image matrix. Observation of the subject
      from optional directions is able to be performed by selecting the view point from
      the optimum image sequence in this image matrix. This system also possesses a
      function to reconstruct 4D models of the subject's moving human body by using 60
      images taken from all directions at one particular time. And this system also has
      the capability to visualize inner structures such as the skeletal or muscular
      systems of the subject by compositing computer graphics reconstructed from the
      MRI data set. We are planning to apply this imaging system to clinical
      observation in the area of orthopedics, rehabilitation and sports science.

PMID- 15455922
TI  - Development of an endoscopic robotic system with two hands for various gastric
      tube surgeries.
AB  - This paper presents the first report on an endoscopic robot with two manipulators
      which performed surgical work to resect the mucosal layer of the stomach of pigs
      without penetrating the body surface. We designed and developed an endoscopic
      surgical robot system which possesses two arm shaped manipulators for various
      kinds of surgery in the gastric tubes. The distal part of the manipulator
      functions as forceps and they are able to hold and handle soft tissues through
      the cooperative efforts of the right and left arms. And it is also able to incise
      the gastric wall by holding an electronic scalpel (brought in from the instrument
      channel) with the manipulator on the right side while opening the sectioning
      plane on the left side which was take out. With this system we succeeded in the
      mucosal resection of a large portion of the stomach wall of a pig during
      experimental surgery. It can be said that this is a new approach robotic surgery
      in the gastric tube with this kind of surgical robot.

PMID- 15455923
TI  - Dynamic deformation of elastic organ model and the VR cockpit for virtual surgery
      and tele-surgery.
AB  - This paper describes a deformable organ model suited for a real-time surgical
      simulation system. This proposed organ model allows us to perform surgical
      maneuvers such as pressing, pinching, various incisions, resection and to show
      the deformation of the inner structures such as blood vessels on our system. At
      the same time, we have been developing a VR cockpit suited for virtual surgery
      and tele-surgery. Using our cockpit, our system allows us to provide the users
      with an environment closely resembling the open surgery situation.

PMID- 15455924
TI  - Wearable schizophrenia treatment with real-time affective context awareness.

PMID- 15455925
TI  - 3D reconstruction of organ surfaces using model-based snakes.
AB  - In this article a new segmentation approach is described that is based on case
      based reasoning and a combination of various established image processing
      concepts described in the current literature. Previously segmented data sets are
      used as anatomical models that represent the cases, called reference models. They
      describe the expected surface shape and representation of the organ in the data
      material. The segmentation task is solved by finding a reference model that is
      similar to the current data set and then by adapting the reference segmentation
      to the current data set. Image segmentation can be divided into the steps
      "determination of the image context", "selection and adjustment of the reference
      model", and "application of the model-based snake". The necessary interaction
      time was reduced by more than 60%, including postprocessing to correct for
      possible segmentation errors.

PMID- 15455926
TI  - Development of a data fusion system using color information for real-time
      intraoperative liver surface measurement.
AB  - The goal of our study is to develop a data fusion system, which enables surgeons
      to easily visualize the inner structures of elastic organs during open surgery.
      We chose the liver as the focus of this study due to its easily deformable nature
      and complex vascular structures. To do so, we propose using preoperative data and
      supplementary intraoperative data. We captured a sequence of liver surface data
      for the intraoperative data by using trinocular stereo and we applied them to the
      preoperative 3D model's surface. Then, we modified the model to fit the
      intraoperative liver condition and portrayed the model's inner structures. With
      this method, we could establish this system.

PMID- 15455927
TI  - NeuroVRAC--a comprehensive approach to virtual reality-based neurological
      assessment and treatment systems.
AB  - We describe a comprehensive software-oriented approach to virtual reality-based
      neuroscientific systems in order to establish an easy to use framework for
      neuroscientific assessment and treatment. We have defined a process model and
      implemented the NeuroVRAC authoring tool for design and execution of experiments
      in virtual environments. Our system enables the modeling of virtual world objects
      and the definition of events, which are used to control the experimental process.
      We have included the virtual test person concept to enhance the sense of presence
      during the execution of virtual reality-based neuroscientific experiments.

PMID- 15455928
TI  - Measurements of the level of surgical expertise using flight path analysis from
      da Vinci robotic surgical system.
AB  - Laparoscopic surgical procedures require precise hand and eye coordination based
      on a 2-dimensional representation of 3-dimensional space. Currently, no metric
      exists to guide the educational process while surgeons are still on the learning
      curve. In this paper, we propose to identify and qualify the patterns of
      movements recorded from the da Vinci robotic surgical system (Intuitive Surgical,
      Sunnyvale CA) that are most consistent with mastery and can define levels of
      proficiency. We have recorded velocities and positions of complex movements made
      by both novice and expert surgeons using da Vinci system and performed geometric
      and statistical analysis of the data.

PMID- 15455929
TI  - Transatlantic medical education: preliminary data on distance-based high-fidelity
      human patient simulation training.
AB  - Advanced training using Human Patient Simulators (HPS) is, for the large part,
      unavailable for the majority of healthcare providers in rural, remote, and less
      developed regions of the world--either due to their separation from the major
      medical education centers or significant fiscal austerity. Remote access to HPS
      based on the Applications Software Provider principles may provide the solution
      to this problem. The medical ASP (MED-ASP) concept proposed and developed by
      MedSMART has been subjected to an extensive qualitative and quantitative
      international test conducted among France, Italy, and USA. Two SimMan HPSs
      (Laerdal, Norway) were used, with one unit based in Ann Arbor, MI, USA, and one
      in Laval, France. While the French site had both remote and hands-on access to
      the simulator, the Italian site could access the HPS only remotely. Simulator
      visualization was provided by 4 remotely operated cameras (Sony, zoom, pan, tilt)
      at each HPS site. HPS-generated vital signs were transmitted to each site
      together with the interactive simulator control panel using a communications hub
      at the MedSMART facility in Ann Arbor. All remote interactions were performed via
      the Internet (TCP/IP) using ISDN and/or ADSL connections at minimum 128 Kbps.
      During the course of training, the trainees were exposed to 3 emergency scenarios
      with the remote expert providing instruction. Interventions were performed either
      remotely (Italy) or remotely and hands-on (France). Quantitative measurement of
      the efficiency of training was performed at the Italian site based on the
      evaluation of video recordings of each session and the assessment of several
      performance measures. At the end of the training program, a Likert scale-based
      assessment test was also given. The trainees showed statistically significant
      (p<0.03 - 0.05) improvement in all testing measures. The Likert scale
      questionnaire revealed overwhelming satisfaction with the simulation-based
      distance training even when the access to the simulator was only remote (Italy).
      Confidence was also significantly improved. The trainees indicated the optimal
      frequency of distance training as one 2 hour-long session twice a month. In
      conclusion, simulation-based distance medical training proved to be a highly
      effective tool in improving emergency medical skills of junior physician trainees
      and, despite initial reservations, neither distance nor language and cultural
      differences posed significant obstacles. The present and historical data from our
      previous work confirm the concept of MED-ASP as a highly efficient tool in both
      national and international medical education and training. Moreover, we now
      validate for the first time the concept of simulation-based, fully interactive
      transatlantic medical ADL that we have proposed in our previous theoretical
      papers. The present experiments prove that training based on advanced
      technologies transcends barriers of distance, time, and national medical
      guidelines. Hence, international simulation-based distance training may
      ultimately provide the most realistic platform for a large-scale training of
      emergency medical personnel in less developed countries and in rural/remote
      regions of the globe.

PMID- 15455930
TI  - Real-time volumetric deformation for surgical simulation using force feedback
      device.
AB  - We have aimed to develop a virtual surgery system that realizes the performance
      of surgical maneuvers on elastic organs and to construct an elastic organ model
      known as sphere-filled model. In this paper we describe a new method of deforming
      volumetric data in real time by using sphere-filled model. As well we modified
      this model to take the interference between soft tissue and rigid tissue to
      consideration. Furthermore basic surgical maneuvers (pushing, pinching and
      incision) and connection with force feedback device are realized on this model
      similarly to our surface model.

PMID- 15455931
TI  - Web-access to a Lung Deposition Model for radiation protection and physiological
      modeling.
AB  - A C++ implementation of the ICRP Lung Deposition Model was validated and made
      accessible by creating a web interface using Perl. Considerable understanding of
      this lung deposition model was obtained and a small number of errors identified
      in the code during this process. Documentation was developed using MathML and
      scalable vector graphics (SVG).

PMID- 15455932
TI  - Virtual reality and interactive 3D as effective tools for medical training.
AB  - CAVE-like displays allow a user to walk in to a virtual environment, and use
      natural movement to change the viewpoint of virtual objects which they can
      manipulate with a hand held device. This maps well to many surgical procedures
      offering strong potential for training and planning. These devices may be
      networked together allowing geographically remote users to share the interactive
      experience. This maps to the strong need for distance training and planning of
      surgeons. Our paper shows how the properties of a CAVE-Like facility can be
      maximised in order to provide an ideal environment for medical training. The
      implementation of a large 3D-eye is described. The resulting application is that
      of an eye that can be manipulated and examined by trainee medics under the
      guidance of a medical expert. The progression and effects of different ailments
      can be illustrated and corrective procedures, demonstrated.

PMID- 15455933
TI  - A mobile and navigated image viewer for surgery--evaluation of precision.
AB  - We report work on a newly developed and ultra compact mobile viewing device,
      called NaviView to display medical imaging data (i.e. from a computer tomograph-
      CT) in situ. The system comprises an optical tracking system to detect both the
      patients and the viewing devices position and display a proportionable part of
      the medical image data on a mobile viewing device. This article describes
      experiments carried out to evaluate the overlay precision of two different
      imaging modalities (i.e. live video and CT) being visualized.

PMID- 15455934
TI  - A hybrid condensed finite element model for interactive 3D soft tissue cutting.
AB  - As requested from practical operations, it is necessary in the design to provide
      the ability to real-time cut and suture the tissue in a surgery simulation apart
      from the deformation simulation. In this paper, we present a deformation model,
      referred as the hybrid condensed FE model, based on the volumetric finite element
      method. The most important advantage of this model is its ability to handle the
      topology change freely with interactive rate in the surgical simulation on
      current PC platform.

PMID- 15455935
TI  - Medical biomodelling in surgical applications: results of a multicentric European
      validation of 466 cases.
AB  - The study started in September 1999 and ended in April 2002. It is based on a
      questionnaire [www.phidias.org] assessing case-related questions due to the
      application of stereolithographic models. Each questionnaire contains over 50
      items. These variables take into account diagnosis, indications and benefits of
      stereolithographic models with view on different steps of the surgical
      procedures: preoperative planning, intraoperative application and overall outcome
      after surgical intervervention. These questionnaires were completed by the
      surgeons who performed operation. Over the time course of our multicentric study
      (30 months), we evaluated 466 cases. The study population consists of n=231 male
      and n= 235 female patients. 54 surgeons from 9 European countries were involved.
      There are main groups of diagnosis that related to the use of a model. Most
      models were used in maxillofacial surgery. The operative planning may help to
      determine the resection line of tumor and optimize reconstructive procedures.
      Correction of large calvarian defects can be simulated and implants can be
      produced preoperatively. Overall in 58 % of all cases a time- saving effect was
      reported. The study strongly suggests, that medical modeling has utility in
      surgical specialities, especially in the craniofacial and maxillofacial area,
      however increasingly in the orthopedic field. Due to our results, medical
      modeling optimizes the preoperative surgical planning. Surgeons are enabeled to
      perform realistic and interactive simulations. The fabrication of implants, its
      design and fit on the model, allow to reduce operation time and in consequence
      risk and cost of operation. In addition, the understanging of volumetric data is
      improved, especially if medical models are combined with standart imaging
      modalities. Finally, surgeons are able to improve communication between their
      patientents and colleagues.

PMID- 15455936
TI  - Anatomically accurate individual face modeling.
AB  - This paper presents a new 3D face model of a specific person constructed from the
      anatomical perspective. By exploiting the laser range data, a 3D facial mesh
      precisely representing the skin geometry is reconstructed. Based on the geometric
      facial mesh, we develop a deformable multi-layer skin model. It takes into
      account the nonlinear stress-strain relationship and dynamically simulates the
      non-homogenous behavior of the real skin. The face model also incorporates a set
      of anatomically-motivated facial muscle actuators and underlying skull structure.
      Lagrangian mechanics governs the facial motion dynamics, dictating the dynamic
      deformation of facial skin in response to the muscle contraction.

PMID- 15455937
TI  - Development of a computer assisted craniofacial surgery planning system.
AB  - Based upon the idea that both facial appearance and functional outcomes of the
      craniofacial surgery need to be predicted in the pre-surgery planning stage, a
      CACSP system has been established. In this system, the input is in vivo CT/MRI
      scan data of patient with craniofacial deformity, anatomical restoration is
      simulated using the medical visualization packages ANALYZE, and the finite
      element analysis of the masticatory system has been integrated to predict the
      functional improvement such as bite force alteration. Preliminary studies in this
      laboratory have revealed the potential of this system.

PMID- 15455938
TI  - Engineering requirements for a haptic simulator for knee arthroscopy training.
AB  - This paper describes the initial development of an innovative haptic device that
      will be integrated into an existing virtual reality training system for knee
      arthroscopy. The resulting system will be called WISHKATS (Warwick, Imperial,
      Sheffield Knee Arthroscopy Training System). This haptic device will enable the
      trainee to feel realistic forces on the probing tool and will work together with
      software, which will simulate tissue deformation. The proposed haptic system is a
      compact, multi-degree of freedom, motorised mechanism with force sensors, and
      will be used to simulate the diagnostic aspects of knee arthroscopy. There are a
      number of problems associated with the development of a suitable haptic system
      and this paper explores the engineering requirements of such a device.

PMID- 15455939
TI  - Mold may not be a severe health menace, but it is still a complex problem.
      Architects must understand air, heat, and moisture flow to achieve better air
      quality.

PMID- 15455940
TI  - [Definition of COPD].

PMID- 15455941
TI  - [Pathogenesis and pathobiology of COPD].

PMID- 15455942
TI  - [Diagnosis of COPD].

PMID- 15455943
TI  - [Pharmacologic treatment of stable COPD].

PMID- 15455944
TI  - [Non-pharmacologic treatment in COPD].

PMID- 15455945
TI  - [Cardiogenic oscillation--utility of classifying types of sleep apnea].
AB  - Cardiogenic pulse waves that travel along the airway wall are captured as airflow
      variations synchronized with the electrocardiogram at the airway exit. We have
      used airflow variations caused by cardiogenic pulse waves (hereinafter referred
      to as cardiogenic oscillation) to classify types of sleep apnea. Pulse waves do
      not travel downstream if there is an airway obstruction or choke point (wave
      speed theory). Thus, cardiogenic oscillation was detectable in central apnea or
      hypopnea, but not in obstructive apnea. In mixed-type sleep apnea, cardiogenic
      oscillation disappeared, and thus airway obstruction was judged to have occurred,
      during central sleep apnea. It was thought that obstructive sleep apnea followed
      central sleep apnea because there was an airway obstruction, although respiratory
      effort resumed after the end of central sleep apnea. The pattern of mixed-type
      sleep apnea was understood from the observation of cardiogenic oscillation.
      Cardiogenic oscillation is useful for not only classifying types of sleep apnea
      but also for detecting an airway obstruction.

PMID- 15455946
TI  - [Application of interlocking detachable coil (IDC) in superselective bronchial
      artery embolization].
AB  - Bronchial artery embolization (BAE) is almost the only effective nonsurgical
      treatment for massive hemoptysis. Metallic coils with plastic fibers are widely
      used as embolic materials. We have introduced an interlocking detachable coil
      (IDC) for BAE. IDC is a mechanically detachable coil, allowing the operator to
      seek the ideal shape until its final release. We compared hemoptysis patients
      treated with conventional metallic coils (24 patients, non-IDC group) with those
      treated with conventional coils and IDCs (26 patients, IDC group). The hemoptysis
      rate after three months is significantly lower in the IDC group than in the non
      IDC group (7.7% vs. 16.3%, p = 0.035 Fisher's exact method). Total procedure time
      (in staged or repetitive BAE cases, procedure times are added together) is
      significantly shorter in the IDC group than in the non-IDC group (3.4 +/- 1.4
      hours vs. 4.4 +/- 2.5 hours, p = 0.040 unpaired t-test). IDC is a useful device
      for BAE. This is the first-ever report documenting the usefulness of IDC for BAE.

PMID- 15455947
TI  - [Surviving case of Legionella pneumonia showing a high level of serum KL-6 and
      complicated with rhabdomyolysis].
AB  - A 66-year-old man was admitted to our hospital with pyrexia up to 40 degrees C
      since one day after taking a public bath. Since multiple infiltrations on the
      lung were shown by chest radiography, severe pneumonia was diagnosed.
      Administration of antibiotics meropenem and erythromycin yielded no detected
      effect. Furthermore, rifampicin induced severe liver dysfunction. Improvement of
      clinical symptoms was seen after ciprofloxacine (CPFX) was given. Interstitial
      pneumonia, increases in KL-6 up to a level of 3545 U/ml and acute respiratory
      failure were improved by taking methylprednisolone. Since Legionella antigen was
      found in the urine, the use of CPFX was continued. Rhabdomyolysis and acute renal
      failure were successfully treated by transfusion, diuretic therapy, and
      glucocorticoid therapy. This was a very rare case of survival after Legionella
      pneumonia complicated with acute respiratory failure, acute renal failure,
      rhabdomyolysis, and interstitial pneumonia accompanied with a high KL-6 level,
      and successfully treated with steroids and CPFX.

PMID- 15455948
TI  - [Case of drug-induced pneumonia followed by sequential bronchoalveolar lavage].
AB  - A 30-year-old woman who had been receiving minocycline for 11 days to treat a
      skin burn presented with high fever and progressive dyspnea. Chest radiography
      demonstrated bilateral pulmonary infiltrates with ground glass opacities. She was
      admitted to our hospital under a tentative diagnosis of minocycline-induced
      pneumonia. Minocycline therapy was discontinued at hospital admission, which led
      to dramatic clinical and radiographic improvement. Bronchoalveolar lavage fluid
      (BALF) analysis three days after the onset of the pneumonia showed increased
      numbers of total cells (7.68 x 10(5)/ml), neutrophils (33%) and eosinophils
      (14%). An increased number of peripheral blood neutrophils was also noted at the
      time of hospital admission. Follow-up evaluations of BALF 10 days and 34 days
      after the onset showed rapidly declining numbers of neutrophils and eosinophils.
      We also measured the levels of several cytokines in BALF, suggesting that TNF
      alpha and IL-8 contributed to the accumulation of neutrophils, whereas IL-5
      contributed to the accumulation of eosinophils. In summary, we report here the
      temporal change in the inflammatory cell and cytokine profile in BALF, serum, or
      both, in a case of drug-induced pneumonia.

PMID- 15455949
TI  - [Case of pulmonary carcinosarcoma and a summary of 17 cases reported in Japan].
AB  - The patient was a 69-year-old man who complained of dyspnea and severe general
      fatigue. Chest CT showed a large tumor (6 x 5 cm) in the left S3 together with
      left pleural effusion. Despite pleurodesis and chemotherapy, he died 1.5 months
      after admission. At autopsy, a final diagnosis of pulmonary carcinosarcoma was
      obtained. We have summarized 17 cases of pulmonary carcinosarcoma reported in
      Japan. All patients were men, and had an average age of 68 years. The majority of
      the patients were heavy smokers. Death was reported in 70% of cases, the median
      survival period being 5 months, whereas the patients reported as living had
      operable cases of T2 tumor without distant metastatic lesions.

PMID- 15455950
TI  - [Case of multi-drug resistant tuberculosis complicated with bronchoesophageal
      fistula].
AB  - A 71-year-old man visited the surgical department of our hospital due to back
      pain in November, 1999. Esophagogram showed bronchoesophageal fistula and a plain
      chest radiograph showed a nodular shadow in the left upper area with left pleural
      effusion. As the symptom disappeared on treatment with an antimicrobial agent, he
      was followed up as an outpatient. In August, 2001, he presented to the
      Respiratory Department of our hospital with low-grade fever and productive cough.
      Since tubercle bacilli were detected in a sputum culture, combined treatment with
      antituberculous chemotherapy was started. But, none of the symptoms were
      improved. These bacilli were identified as being multi-drug-resistant. After the
      chemotherapy regimen was changed, the symptoms disappeared and the
      esophagorespiratory fistula was closed. We report a rare case of
      esophagorespiratory fistula with multi-drug resistant tuberculosis, which was
      improved by chemotherapy.

PMID- 15455951
TI  - [Fatal acute exacerbation of idiopathic pulmonary fibrosis/usual interstitial
      pneumonia initially in the right lung after surgery lobectomy for left lung
      cancer].
AB  - A tumor was found in the left S10 in a chest CT scan of a 72-year-old male
      patient with idiopathic pulmonary fibrosis/usual interstitial pneumonia
      (IPF/UIP). He underwent left lower lobectomy and resection of the hilar and
      mediastinal lymph nodes under video-assisted thoracoscopic surgery. The
      histopathological evaluation disclosed a well-differentiated squamous cell
      carcinoma (T1N0M0; stage IA) associated with UIP. On the sixth postoperative day,
      a severe hypoxemia (PaO2 48 mmHg) developed, and the chest CT showed diffuse
      ground glass opacity (GGO) in the right lung. A diagnosis of acute exacerbation
      of IPF/UIP was made, and steroid pulse therapy with cyclosporin A was started.
      However, despite this therapy, the diffuse GGO extended to both lung fields, and
      the patient died of respiratory failure 82 days later. The histopathology at
      autopsy demonstrated diffuse alveolar damage due to UIP that was consistent with
      acute exacerbation of IPF/UIP. It is suggested that the acute exacerbation of
      IPF/UIP could have been triggered by a high concentration of oxygen or mechanical
      lung injury during the patient's surgery.

PMID- 15455952
TI  - [Case of chronic eosinophilic bronchiolitis associated with bronchial asthma].
AB  - A 62 year-old woman presented with diffuse, centriacinar nodular densities on
      chest radiography and CT, and an increase of peripheral blood eosinophils, four
      years after diagnosis of bronchial asthma. Diffuse panbronchiolitis was
      diagnosed, and was treated with erythromycin for a long period. One year later,
      she noticed exertional dyspnea, and her chest radiograph showed increased nodular
      densities. Lung biopsy under video-assisted thoracoscopy was performed, and
      revealed chronic bronchiolitis with eosinophilic infiltration, and focal,
      peribronchiolar eosinophilic infiltration in the alveolar septa and alveoli. She
      was treated with prednisolone, and her symptoms and nodular densities on chest
      radiography and CT were improved. We consider that the clinico-pathological
      findings of this case are consistent with those of chronic eosinophilic
      bronchiolitis, which has recently been reported in Japan. This case is different
      from previously reported ones in that eosinophilic bronchiolitis appeared in the
      course of bronchial asthma, suggesting the possibility that eosinophilic
      bronchiolitis may be accompanied with bronchial asthma or eosinophilic pneumonia.

PMID- 15455953
TI  - [Case of malignant lymphoma arising from the posterior mediastinum, with pleural
      effusion].
AB  - We report a rare case of malignant lymphoma arising from the posterior
      mediastinum with bilateral pleural effusion. A 71-year-old man was admitted to
      our hospital for evaluation of a posterior mediastinal tumor and bilateral
      pleural effusion revealed on a chest CT scan. Because no tumor tissue could be
      obtained by fiberbronchoscopy, video-assisted thoracoscopic surgery was
      performed. The tumor sample was composed of large, atypical lymphocytes positive
      for CD20 on immunohistochemical analysis. A diagnosis of diffuse large B cell
      lymphoma was made from the typical histological features. The patient was treated
      with combination chemotherapy (CHOP) and rituximab and improved dramatically.

PMID- 15455954
TI  - [Case of interstitial pneumonitis induced by a Chinese herbal medicine, bofu
      tsusho-san].
AB  - The patient was a 64-year-old woman. She had complained of dyspnea during
      exercise, productive cough, and pyrexia for two months after treatment to reduce
      her body weight with a Chinese herbal medicine, bofu-tsusho-san. This symptom
      worsened gradually, and she was admitted to our hospital for the examination and
      therapy. Chest radiography and CT scanning on admission showed ground-glass
      attenuation with partial consolidation. Replacement of the medicine with
      treatment with oxygen and few medications for two weeks, made her condition well.
      The result of DLST for the herbal medicine, Bofu-tsusho-san was negative, but we
      strongly think it induced pneumonitis. The Chinese herbs ogon and kanzo which are
      ingredients of bofu-tsusho-san, can cause drug-induced pneumonitis. In
      conclusion, care should be taken if side effects, hypersensitivity, lung disease,
      liver injury, or other morbid conditions arise during the use of herbal
      medicines, because these disorders may lead to serious illness.

PMID- 15455955
TI  - [Case of rheumatoid arthritis presenting with pulmonary tuberculosis].
AB  - A 72-year-old man who had been suffering from rheumatoid arthritis for 25 years
      developed pulmonary tuberculosis after treatment with infliximab. He had been
      receiving this treatment since December 2003. Forty-six days later, a fever
      developed and the patient was hospitalized on February 3, 2004. Chest radiography
      and chest CT showed an infiltrative shadow with cavity formation. Mycobacterium
      tuberculosis was detected in the sputum. Infliximab is a monoclonal antibody
      toward tumor necrosis factor alpha (TNFalpha). It has been reported that
      infliximab increases the risk of tuberculosis in patients with rheumatoid
      arthritis in Europe and North America. This is the first case of pulmonary
      tuberculosis in a patient treated with infliximab in Japan.

PMID- 15455956
TI  - Unsedated endoscopy: you don't get a medal for it!

PMID- 15455957
TI  - Proton pump inhibitors and iron deficiency: is the connection real?

PMID- 15455958
TI  - Who is willing to undergo endoscopy without sedation: patients, nurses, or the
      physicians?
AB  - OBJECTIVES: Some studies suggest that the majority of the United States
      population is now willing to undergo unsedated endoscopy. We studied the
      willingness of patients, nurses, and physicians to undergo endoscopy without
      sedation. METHODS: Adult patients presenting to us for outpatient endoscopy at
      two large tertiary care level 1 trauma hospitals were asked to fill out a survey
      questionnaire recording their demographic information, prior experience with
      endoscopy and sedation, and whether they were willing to undergo unsedated
      endoscopy. Their anxiety level was assessed using the Beck Anxiety Inventory.
      After the endoscopic procedure, patients were asked whether they had any change
      in their decision regarding unsedated endoscopy. A random convenience sample of
      physicians and nurses were also given a questionnaire asking about their
      experience with endoscopy and whether they were willing to undergo such
      procedures without sedation. RESULTS: A total of 127 patients, 117 nurses, and 51
      physicians participated in the study. Only 19.5% of patients were willing to
      undergo upper endoscopy without sedation. Among patients, the willingness dropped
      to 6.75% postprocedurally. Results were similar for colonoscopy. Physicians were
      least likely to agree to an unsedated procedure (2.2%). Gastroenterology (GI)
      nurses were more likely to undergo unsedated esophagogastroduodenoscopy (39.3%)
      as opposed to non-GI nurses (7.1%, P < 0.001). 19.6% of GI nurses agreed to
      unsedated colonoscopy versus 0% in the non-GI group (P = 0.001). Preprocedure
      anxiety level was not found to be a predictor for willingness to undergo
      unsedated endoscopy. Female patients were more likely to forego sedation
      preprocedurally (OR = 5.75; 95% CI = 2.05-16.2). However, postprocedurally,
      gender was no longer a significant predictor. Similarly, among the nurses and
      physicians, neither age nor gender was a significant predictor of willingness to
      undergo unsedated endoscopy. Patients with a high school (OR = 0.01; 95% CI =
      0.01-0.06) or associates degree (OR = 0.02; 95% CI = 0.01-0.35) were less likely
      to forego sedation. CONCLUSION: In contrast to reports from some major medical
      centers, the current study found that most patients as well as medical
      professionals were unwilling to undergo endoscopy without sedation.

PMID- 15455959
TI  - Physical activity trends in South Carolina, 1994-2000.
AB  - OBJECTIVES: During the 1990s, physical activity recommendations and surveillance
      methods were developed in an attempt to increase and monitor, respectively,
      regular physical activity prevalence rates. For this article, Behavioral Risk
      Factor Surveillance System data were analyzed to determine whether regular
      physical activity proportions in South Carolina adults changed from 1994 to 2000.
      The physical activity prevalence rates for South Carolina were compared with
      national rates and Healthy People 2000 goals to measure progress. The rate of
      physical activity counseling by physicians and other health professionals was
      also analyzed from 1998 to 1999. METHODS: Total subjects included 10,495 adults
      ages 18 years and older from South Carolina and 545,445 from the remainder of the
      United States. Using random-digit dialing procedures in 1994, 1996, 1998 and
      2000, the two most frequent types of leisure-time physical activity performed in
      the past month were identified. For activities listed, the frequency (days/wk)
      and duration (minutes/d) were obtained. Linear regressions were performed on
      regular physical activity and inactivity for the total population and by gender,
      race, age, and body mass index (BMI). Data pertaining to whether or not a
      physician or other health professional had provided physical activity counseling
      were also obtained for 1998 and 1999. RESULTS: From 1994 to 2000, the proportion
      of South Carolina adults participating in regular leisure time physical activity
      significantly increased (10.8%). Interestingly, the prevalence of regular
      physical activity in the rest of the nation remained unchanged during this time.
      Although significant increases were observed in nearly all subgroups, physical
      activity prevalence rates for South Carolina adults lagged behind national levels
      and did not meet Healthy People 2000 goals. Physical activity counseling by
      physicians and other health professionals increased from 1998 (24.1%) to 1999
      (30.4%). CONCLUSIONS: While it is not known what factors influenced regular
      physical activity from 1994 to 2000, they seem to have been equally effective in
      South Carolina adults of both genders, both races, regular and overweight status,
      and nearly all age groups. Despite these positive trends, additional efforts are
      needed to develop and implement effective community and primary care physical
      activity interventions that facilitate improvements among the nearly two-thirds
      of South Carolina adults who do not participate in sufficient physical activity
      to reap significant health benefits.

PMID- 15455960
TI  - Pancreatic tumors in patients with lung malignancies: a spectrum of
      clinicopathologic considerations.
AB  - OBJECTIVES: Lung cancer and pancreatic cancer are the most lethal tobacco
      associated malignancies. To elucidate possible clinical interrelationships, the
      authors reviewed the clinicopathologic characteristics of patients treated for
      both pulmonary and pancreatic neoplasms. METHODS: Patients presenting with a
      potentially resectable pancreatic mass and a diagnosis of metachronous malignant
      neoplasm of the lung were studied by retrospective chart audit and review of
      histopathologic material. RESULTS: Seven patients were identified over 6 years,
      representing five different clinical entities: metachronous presence of lung
      cancer and pancreatic cancer (n = 3), lung cancer metastatic to the pancreas (n =
      1), lung cancer with a benign pancreatic neoplasm (n = 1), periampullary cancer
      metastatic to the lung (n = 1), and malignant melanoma metastatic to both lung
      and pancreas (n = 1). A tobacco history was present in all patients but one.
      Primary treatment modality was complete resection of isolated sites whenever
      feasible (lung resection, n = 6; pancreatic resection, n = 5). In four cases, a
      differential diagnosis of adenocarcinomas of both lung and pancreas was obtained
      after cytokeratin (CK) 7 and CK 20 immunohistochemistry. All patients with
      evidence of nodal or visceral metastasis from either primary site (n = 4) died
      within 5 to 9 months after the last operation. Three of four patients who had
      undergone resection of both pulmonary and pancreatic tumors were alive between 17
      and 67 months after the last operation. All three survivors had presented with
      early disease stages and/or a protracted course (diagnostic interval, 16-66
      months). CONCLUSIONS: Our experience with neoplastic conditions that can involve
      lungs and pancreas metachronously may be useful to the clinician who is
      confronted with a similar situation. If therapeutic decision-making depends on
      differential diagnostic analysis, examination of CK 20 expression appears to be
      helpful. Although biologically favorable circumstances are rarely present, long
      term survival seems possible after complete operative treatment in selected
      patients with early-stage disease.

PMID- 15455961
TI  - Long-distance fixed-wing transport of obstetrical patients.
AB  - OBJECTIVES: Aeromedical obstetrical transports are mostly performed utilizing
      helicopters. The program here reviewed performs mostly fixed-wing transports. The
      purpose of the current study is to review our fixed-wing transfers and identify
      the complications encountered. METHODS: A retrospective review was conducted of
      the fixed-wing obstetrical air transports performed by the StatCare aeromedical
      transport service from July 1, 2000 through June 30, 2002. Information on each
      patient (age, gestational age, gravida status, diagnosis, preflight physical
      examination) was collected using a data sheet. Also noted were any described
      complications. RESULTS: During the 24-month study period, 80 fixed-wing
      transports were performed. In-flight complications included nausea and vomiting
      (80%), increased contractions (8.8%), hypertension (1.3%), hypotension (1.3%),
      decreased maternal respiratory drive (1.3%), and infiltrated intravenous line
      (1.3%). CONCLUSIONS: The complications encountered during long-distance fixed
      wing aeromedical transport of obstetrical patients include nausea and vomiting,
      increased contractions, hypertension, hypotension, decreased maternal respiratory
      drive, and an infiltrated intravenous line.

PMID- 15455962
TI  - A novel specific prophylaxis for menstrual-associated migraine.
AB  - OBJECTIVES: Few migraine prophylactic therapies have demonstrated a 50% reduction
      in headaches. Even when successful, the economic burden of prophylaxis can
      discourage widespread usage. This article presents a pilot study of a novel,
      effective, specific, and inexpensive prophylactic strategy for menstrual
      associated migraine. MATERIALS AND METHODS: Eleven women with menstrual
      associated migraine and fewer than 14 days of headache per month were identified
      from prospective enrollment at a gynecology practice and retrospective chart
      review at a headache center. Exclusion criteria included current use of
      prophylactic therapy for migraine. METHODS: Patients received open-label therapy
      with an oral contraceptive containing 20 microg ethinyl estradiol on days 1 to
      21, supplemented with 0.9 mg conjugated equine estrogens on days 22 to 28.
      Headache intensity and bleeding were recorded in diaries that plotted headache
      days by oral contraceptive pill days. RESULTS: All of the patients achieved at
      least a 50% reduction in number of headache days per cycle (mean 77.9%
      reduction); 10 of the 11 women achieved at least a 50% reduction in weighted
      headache score (mean 76.3% reduction). CONCLUSIONS: All currently available
      estrogen-containing oral contraceptives produce a premenstrual fall in ethinyl
      estradiol concentration equal to or greater than 20 microg. Estrogen
      supplementation during the placebo week can reduce the magnitude of this fall to
      less than 20 microg. When the decline is limited to the equivalent of 10 microg
      ethinyl estradiol, menstrual-associated migraine is prevented. At an average cost
      of six dollars per headache-day prevented, this represents an effective and
      inexpensive strategy for a common migraine trigger.

PMID- 15455963
TI  - Adult outcome of child and adolescent attention deficit hyperactivity disorder in
      a primary care setting.
AB  - OBJECTIVES: To determine the adult status of children and adolescents previously
      diagnosed with attention deficit hyperactivity disorder (ADHD). METHODS: From a
      consecutive sample, a case series from a primary care, private physician, office
      based practice was evaluated. Seventy-seven adults were eligible, having been
      diagnosed with ADHD as children and adolescents by Diagnostic and Statistical
      Manual of Mental Disorders, Revised Third and Fourth Editions criteria. Seventy
      three adults were available for interviews. Parents and/or significant others
      were also interviewed. The same criteria used originally were employed in the
      adult follow-up analysis. Main outcome measures included rates of adult ADHD,
      other psychiatric disorders, and educational attainment. RESULTS: Of 73
      participants, only 4 (5.5%) had retained ADHD into adulthood. Sixty-nine (94.5%)
      did not have adult ADHD. The majority of the cohort did not exhibit any disabling
      psychopathology, and most had achieved positive educational attainment.
      CONCLUSIONS: Adult follow-up of children and adolescents diagnosed with ADHD
      shows adult ADHD is rare in primary care. The data suggests that clinicians can
      have the greatest impact on ADHD by concentrating on the evaluation and
      management of children and adolescents with the disorder.

PMID- 15455964
TI  - Photodynamic therapy and endoscopic mucosal resection for Barrett's dysplasia and
      early esophageal adenocarcinoma.
AB  - BACKGROUND: Endoscopic mucosal resection (EMR) and endoscopic ablation with
      porfimer sodium photodynamic therapy (PDT) have recently been combined to improve
      the accuracy of histologic staging and remove superficial carcinomas. MATERIALS
      AND METHODS: All patients with Barrett's esophagus and high-grade dysplasia were
      evaluated with computed tomography and endosonography. Patients with nodular or
      irregular folds underwent EMR followed by PDT. RESULTS: In three patients,
      endoscopic mucosal resection upstaged the diagnosis to mucosal adenocarcinoma
      (T1N0M0). PDT successfully ablated the remaining glandular mucosa. Complications
      were limited to transient chest discomfort and odynophagia. CONCLUSIONS: The use
      of EMR resection in Barrett's high-grade dysplasia patients with mucosal
      irregularities resulted in histologic upstaging to mucosal adenocarcinoma,
      requiring higher laser light doses for PDT. PDT after EMR appears to be safe and
      effective for the complete elimination of Barrett's mucosal adenocarcinoma. EMR
      should be strongly considered for Barrett's dysplasia patients being evaluated
      for endoscopic ablation therapy.

PMID- 15455965
TI  - Compassionate-use oxaliplatin with bolus 5-fluorouracil/leucovorin in heavily
      pretreated patients with advanced colorectal cancer.
AB  - OBJECTIVES: The efficacy of a concomitant oxaliplatin/bolus 5
      fluorouracil/leucovorin regimen in 123 heavily pretreated patients with advanced
      colorectal cancer was evaluated. Patients with an Eastern Cooperative Oncology
      Group performance status of 0 to 2 and radiographically progressive cancer which
      failed to respond to between two and five prior treatment modalities were
      consented and enrolled. METHODS: Patients received oxaliplatin on day 1 of weeks
      1, 3, and 5 of an 8-week cycle. 5-fluorouracil/leucovorin was administered on day
      1 of weeks 1 through 6. RESULTS: Grade 3 to 4 toxicities were as follows:
      diarrhea 30%; vomiting 11%; hematologic < 3%; peripheral neuropathy 2.5%. Of the
      101 patients evaluable for response, 7% achieved a partial response (median
      duration 4.25 mo), 1 patient achieved a minor response (7 mo), and 31% had stable
      disease (median duration 6.08 mo). The median time to progression was 3.6 months.
      CONCLUSION: This regimen in heavily pretreated patients with disseminated
      colorectal cancer is of modest benefit, often at the expense of considerable
      gastrointestinal toxicity. It appears that the use of oxaliplatin/bolus 5
      fluorouracil/leucovorin is more toxic than oxaliplatin/infusional 5-fluorouracil
      and possibly less effective.

PMID- 15455966
TI  - Concussion in athletes.

PMID- 15455967
TI  - Management of the critically injured athlete: packaging of head and cervical
      spine injuries.
AB  - Emergency medical personnel must take extreme caution when evaluating and
      treating an athlete with a suspected head or spine injury. While head and neck
      injuries may continue to be life threatening, the proper management of these
      injuries may prevent further injury from occurring.

PMID- 15455968
TI  - Low back pain in running-based sports.

PMID- 15455969
TI  - The female athlete.

PMID- 15455970
TI  - Exercise-induced asthma.

PMID- 15455971
TI  - Sudden cardiac death in athletes.

PMID- 15455972
TI  - Current issues in sports nutrition in athletes.

PMID- 15455973
TI  - Foot orthoses in sports medicine.

PMID- 15455974
TI  - The preparticipation athletic exam process.

PMID- 15455975
TI  - Sports medicine: the primary care perspective.

PMID- 15455976
TI  - Coding and reimbursement in sports medicine.

PMID- 15455977
TI  - Supplements and athletes.
AB  - Supplements have become a staple with athletes. Athletes take supplements to
      enhance their performance through replenishment of real and perceived
      deficiencies, anabolic action of stimulants, increased energy and alertness, and
      for weight control. Physicians who deal with athletes should be aware of the
      supplements being utilized by athletes, the athletes' desired effects and the
      efficacy of the supplement, the adverse effects, and whether the supplement is
      banned by leagues or organizations in which the athletes are competing. For those
      athletes who are regularly drug tested for performance enhancers, it is important
      to remember that one cannot be 100% sure that any supplement will not result in a
      positive drug test, because there is no independent agency certifying purity.

PMID- 15455978
TI  - Sports medicine in youth athletes.

PMID- 15455979
TI  - Exercise physiology and its role in clinical sports medicine.
AB  - Exercise physiology plays an important role in the practice of clinical sports
      medicine. Exercise physiology research has identified important effects of
      exercise on the body's systems, tissues, and cells. Ongoing research is
      investigating the role of exercise in subcellular, molecular, and chemical
      processes. Increasingly, sports medicine physicians and other practitioners are
      using the findings of this research to help athletes achieve peak performance,
      and nonathletes achieve better health through exercise. Many areas of sports
      medicine practice, including exercise testing, safety, performance evaluation,
      correction of training problems, and prevention of problems that affect specific
      populations (eg, older athletes, women, children), benefit from the application
      of exercise physiology theory and research. The continued demand for athletes at
      all levels to be better, faster, and stronger, combined with the national focus
      on getting all Americans involved in some form of physical activity, will require
      that sports medicine practitioners and exercise physiologists increasingly work
      together to optimize sports and exercise performance, health, and safety.

PMID- 15455980
TI  - Effect of omeprazole on oral iron replacement in patients with iron deficiency
      anemia.
AB  - Hypochlorhydric states such as atrophic gastritis and partial gastrectomy have
      long been known to cause iron deficiency anemia. However, studies to date have
      failed to show a similar association with omeprazole, a proton pump inhibitor
      that also produces achlorhydria. These studies, however, have primarily involved
      nonanemic, iron-replete individuals. The effect of the drug has not been studied
      in patients with established iron deficiency, and to our knowledge the patients
      presented here are the first of their kind to be reported. Our observations
      support the probability that the profound hypochlorhydria induced by omeprazole
      may indeed impair the optimal absorption of orally administered iron in iron
      deficient individuals, precluding them from obtaining therapeutically adequate
      amounts to establish the positive balance necessary for the resolution of anemia
      and the replenishment of stores. The possible explanations for this phenomenon
      are also discussed.

PMID- 15455981
TI  - Desquamative interstitial pneumonia and hepatitis C virus infection: a rare
      association.
AB  - Extrahepatic manifestations of hepatitis C virus (HCV) infection are common. The
      authors report the unusual occurrence of desquamative interstitial pneumonia
      (DIP) in a patient with HCV. An immunologic response to HCV infection may have a
      role in the pathogenesis of DIP in patients with chronic HCV. Since DIP is
      treatable, HCV patients with pulmonary infiltrates should be thoroughly
      investigated for this disorder. In our experience, the use of steroids in HCV
      associated DIP improved the patient's respiratory status without increasing the
      viral load.

PMID- 15455982
TI  - Myonecrosis in sickle cell anemia: case report and review of the literature.
AB  - Vascular occlusion is responsible for most of the severe complications of sickle
      cell anemia (SCA). The involvement of muscle and fascia is uncommon in SCA, but
      myonecrosis may occur in SCA crisis. The data accumulated in the literature is
      limited to only a few reports describing mainly adult patients presenting with
      severe muscular pain. We report a rare case of sickle myonecrosis and secondary
      involvement of an associated joint after a severe painful crisis in the left
      thigh.

PMID- 15455983
TI  - Mucinous cystic neoplasms of the pancreas.
AB  - Mucinous cystic neoplasms of the pancreas (MCNP) are rare tumors with
      presentation and findings that differ in most cases from pancreatic pseudocysts.
      A simple pancreatic cystic lesion in a younger-aged patient with a history of
      pancreatitis and endoscopic retrograde cholangiopancreatography (ERCP)
      demonstration of ductal communication with the cyst strongly suggests the
      diagnosis of a benign pseudocyst. MCNP may have extensive areas without an
      epithelial lining, adding histologic sampling error to the potential for
      confusing these two entities. Pancreatic pseudocysts are benign lesions treated
      by enteric drainage procedures, while MCNP have significant malignant potential,
      and resection is advised. Even when clinical presentation and imaging are
      persuasive for a benign cyst, MCNP of the pancreas should be considered in
      planning, evaluation, and treatment.

PMID- 15455984
TI  - Fibrosing colonopathy in an adult cystic fibrosis patient after discontinuing
      pancreatic enzyme therapy.
AB  - Fibrosing colonopathy, a complication of cystic fibrosis, has generally been
      reported in young children with exposure to high doses of pancreatic enzymes. The
      authors report the case of a 25-year-old male with cystic fibrosis who presented
      with gradually progressive symptoms of bowel obstruction. Pathologic examination
      of the right colon revealed findings consistent with fibrosing colonopathy. This
      case is distinctive because of the adult presentation, and because the patient's
      symptoms developed long after he had discontinued taking a high-strength enzyme
      preparation. This case suggests that multiple etiologic factors, and not simply
      exposure to pancreatic enzymes, may result in fibrosing colonopathy in adults
      with cystic fibrosis.

PMID- 15455985
TI  - Eosinophilic gastroenteritis, ascites, and pancreatitis: a case report and review
      of the literature.
AB  - Eosinophilic gastroenteritis is an inflammatory disorder of the gastrointestinal
      tract in which eosinophilic infiltration occurs in the gut layers. A case of
      subserosal eosinophilic gastroenteritis was diagnosed in a patient with abdominal
      pain, eosinophilic ascites, and pancreatitis. To our knowledge, this is the first
      case report of eosinophilic gastroenteritis associated with concurrent
      eosinophilic ascites and pancreatitis.

PMID- 15455986
TI  - Successful ivermectin treatment of hepatic strongyloidiasis presenting with
      severe eosinophilia.
AB  - A 49-year-old, previously healthy nurse presented with hepatic lesions and severe
      peripheral eosinophilia due to strongyloidiasis. Imaging studies of the abdomen
      showed predominantly peripheral, confluent hepatic lesions. The hepatic lesions
      and eosinophilia did not show any improvement with albendazole, but completely
      resolved with ivermectin treatment. Our findings suggest that Strongyloides
      stercoralis can present with isolated focal hepatic lesions and severe
      eosinophilia, and resolves with ivermectin treatment.

PMID- 15455987
TI  - Microscopic polyangiitis presenting with liver dysfunction preceding rapidly
      progressive necrotizing glomerulonephritis.
AB  - The authors describe a 52-year-old woman diagnosed with microscopic polyangiitis.
      She presented with abnormal liver function tests accompanied by fever, headache,
      and fatigue. Two months later, rapidly progressive necrotizing glomerulonephritis
      developed together with seropositivity for perinuclear antineutrophil cytoplasmic
      antibody. Although liver dysfunction from microscopic polyangiitis is very rare,
      especially at presentation, this diagnostic possibility should be kept in mind to
      permit prompt consideration of steroid therapy.

PMID- 15455988
TI  - Pneumonia presenting as singultus.

PMID- 15455989
TI  - Virchow's triad?

PMID- 15455990
TI  - Septic discitis as a cause of intractable back pain: deja vu.

PMID- 15455991
TI  - Reducing patient aggression and hostility in primary care with urine drug
      testing.

PMID- 15455992
TI  - Erroneous claims of priority in publication.

PMID- 15455993
TI  - The patient's page.

PMID- 15455994
TI  - The wrongful birth tort: a policy analysis and the right to sue for an
      inconvenient child.

PMID- 15455995
TI  - The development of scoliosis following pinealectomy in young chickens is not the
      result of an artifact of the surgical procedure.
AB  - Pinealectomy in young chickens consistently results in scoliosis which has many
      characteristics similar to those seen in adolescent idiopathic scoliosis. The
      mechanism underlying this phenomenon remains a mystery and it is not yet entirely
      clear whether some unidentified aspect of the extensive surgery is the major
      factor rather than the removal of the pineal gland. Four different types of
      pinealectomy surgery were performed on young chickens as well as deliberate
      damage to the cerebral cortex which simulated the extreme of any accidental
      damage that might occur during surgery. Scoliosis was assessed from weekly
      radiographs. No differences in incidence of scoliosis, degree of severity or
      pattern of curve development were observed for any of the experimental groups
      when compared with controls. In all groups approximately 55% of the chickens
      developed scoliosis that progressed rapidly. Different pinealectomy procedures
      and deliberate damage to the cerebral cortex produce scoliosis in young chickens
      with the same incidence and characteristics. This suggests strongly that the
      mechanism behind the phenomenon is due to the removal of the pineal gland and not
      some artifact of the extensive surgery. The pinealectomy model in young chickens
      is proving to be a good model for studying AIS in humans. An understanding of the
      mechanism underlying this phenomenon has the potential to provide further
      insights into the aetiology of AIS and can lead to the development of novel
      treatement methods.

PMID- 15455996
TI  - Scoliosis and cavus foot. Is there a relationship? Study in referrals, with and
      without scoliosis, from school screening.
AB  - BACKGROUND: The correlation of idiopathic scoliosis and cavus foot has been
      previously reported. This has been ascribed to possible lesions related to
      muscular imbalance influenced by the central nervous system. The aim of this
      study is the assessment of this correlation. MATERIAL AND METHOD: 3,544 children
      were studied, (1,765 boys and 1,779 girls, aged from 6 to 18 years) from a school
      screening program of our department. A number of measurements were assessed
      including the angle of trunk inclination (ATI) in standing and sitting forward
      bending positions using the Pruijs scoliometer and the morphology of the sole
      shape using the Harris & Beath footprint mat. The 6 types footprint
      classification was used for foot shape as it was elsewhere reported. Type 1 in
      this classification represents typical and type 2 light cavus foot. In a first
      main group, 317 children were referred, who presented with ATI> or =7 degrees,
      and were divided into 2 subgroups. The 1st subgroup included n=264 children with
      body asymmetry but with no scoliosis and the 2nd subgroup included n=53 scoliotic
      children (Cobb angle >10 degrees). The 2nd main group included 3 227 children
      without asymmetry. The presence of cavus foot (footprint type 1 and 2) in these 2
      groups was searched. Statistical analysis was performed using SPSS package.
      RESULTS: n=4 (7.54%) out of the 53 scoliotics had cavus foot [n=1 (1.88%) typical
      and 3 (5.66%) light cavus foot], while n=55 (20.8%) out of 264 non-scoliotic
      referrals showed n=9 (3.4%) typical and n=46 (17.42 %) light cavus foot. These
      readings prove that there is no statistical correlation between idiopathic
      scoliosis and cavus foot. Additionally n=3227 normal symmetric children, n=620
      (19.21%), presented cavus foot, [footprints type 1 n=106 (3.28%) and type 2 n=
      514 (15.92%)], which is a percentage higher than that of the scoliotic
      population. CONCLUSIONS: The significant correlation between idiopathic scoliosis
      and cavus foot as it has been elsewhere reported was not verified in this study.
      On the contrary it is emphasized that the percentage of cavus foot was traced
      higher in the general healthy population than that in the small and moderate
      scoliotic curves studied.

PMID- 15455997
TI  - A comparison between bipedal and quadripedal rats. Do bipedal rats actually
      assume an upright posture?

PMID- 15455998
TI  - The relationship between minor asymmetry and early idiopathic scoliosis.
AB  - School scoliosis screening programmes have consistently produced large numbers of
      referrals with minimal trunk asymmetry which then must be assessed, evaluated and
      perhaps investigated and monitored over a period of time before it is felt safe
      to discharge them as 'non-progressive.' Beyond measures to reduce their number,
      they have received less attention than the more interesting cases requiring
      treatment or surgery, which they outnumber to a significant extent. Examination
      of the figures from a historical database shows that the patients have no greater
      probability of developing significant scoliosis than their 'normal' peers . So
      they should not be classed as scoliosis but they are still relevant to the
      broader picture of aetiology.

PMID- 15455999
TI  - Dysfunction of the autonomic nerve system (ANS) in the aetiopathogenesis of
      adolescent idiopathic scoliosis.
AB  - Despite much evidence of its existence, the relation between impaired ANS
      function and the aetiopathogenesis of AIS has attracted surprisingly little
      attention. Studies have shown that the left breast of girls with right convex
      thoracic AIS is significantly more vascular than the right one and that the mean
      concave minus convex rib length in women with thoracic IS is significantly
      greater than the left minus right rib length in normal women. Moreover in growing
      rabbits unilateral regional sympathectomy by resection of intercostal nerves
      carrying sympathetic fibers results in hypervascularity of the soft tissues,
      increased rib growth on the side of the operation and thoracic scoliosis convex
      to the opposite side. The results of these and of other reports provide
      sufficient indication of a relation between ANS dysfunction and IS, and open new
      views for research on the connection between the aetiology and pathogenesis of
      the thoracospinal deformity.

PMID- 15456000
TI  - Idiopathic scoliosis and quality of life.
AB  - Scoliosis may lead to multiple impairments depending on its seriousness. Here we
      have to make the distinction between direct impairments in the physical field and
      indirect impairments in the psychosocial field. The findings of different studies
      indicate that the psychosocial situation in juvenile and adult scoliotic patients
      is characterized by increased strain. The present study is meant to answer the
      question in which fields of quality of life female scoliotic patients are
      impaired and if these impairments are dependent of age or seriousness of illness
      (Cobb angle). Between May 1998 and February 1999, 226 female patients with
      idiopathic scoliosis were surveyed in a special clinic for spinal deformities
      with the help of different quality of life measuring instruments (SF-36, BFW,
      STAIK) and were compared with norm values. Women with idiopathic scoliosis were
      questioned with the help of an age adapted set of questionnaires containing
      questions referring to the health related quality of life (SF-36, BFW, STAIK).
      The results were compared to the norm values and examined in uni- and multivariat
      procedures (MANOVA) in order to find out if age and seriousness of illness (Cobb
      angle) have any impact on the quality of life. In comparison to the norm random
      sample, the juvenile female scoliosis patients showed a less positive point of
      view towards life (p = .001) and were easier subject to depressive moods (p =
      .021). The increased strain of adult patients was shown both in the psychic field
      (p < .001) and in the physical field (p < .001) (SF-36). These results are
      largely independent of the seriousness of illness (Cobb angle) and of the
      patients' age. The results indicate that idiopathic scoliosis in children,
      adolescents and adults can be regarded as a risk factor for the impairment of
      health related quality of life and thus stress the importance of psychosocial
      offers during a patient-orientated scoliosis treatment in order to improve the
      management of scoliosis.

PMID- 15456001
TI  - Menarche in scoliotic and nonscoliotic Mediterranean girls. Is there any relation
      between menarche and laterality of scoliotic curves?
AB  - There is a controversy in the current literature concerning the age at menarche
      between scoliotic and nonscoliotic girls. The aim of this study is to elucidate
      this issue in the Mediterranean school aged girls. MATERIAL AND METHODS: The
      menarche of 1,305 nonscoliotic girls (mean age 12,3 years, range 7,41 to 18,41
      years, SD 2,5 years) and of 105 scoliotic girls (mean age 14.15 years, range 7.47
      to 18.97 years, SD=2.7 years) was studied. These two groups originate from a
      total population of 4,535 schoolchildren who were examined during school
      screening (2,245 girls, 2,290 boys). The Angle of Trunk Inclination (ATI) greater
      or equal to 7 degrees, measured with the Pruijis Scoliometer was used as a pass
      fail criterion for radiological examination. The diagnosis of scoliosis was
      defined as the finding of a Cobb angle greater or equal to 10 degrees on a
      standing postero-anterior radiograph of the spine. Statistical analysis was
      performed using the SPSS statistical program. RESULTS: 476 girls out of 1,305
      nonscoliotic girls (36,50%, mean age 14,04 years, range 9.04 to 18,21 years,
      SD=1.59 years) had menarche (mean age at menarche 12,07 years, SD 1,35 years,
      range from 7,63 to 14,59 years), while the remaining 829 girls (63,50%, mean age
      11,09 years, SD 2,09 years, range 7,41 to 18,47 years) had not any. On the other
      hand, 77 out of the 105 scoliotic girls had menarche (73,33%, mean age 15,29
      years, SD 1,54 years, range 11,35 to 18,97 years). The mean age at menarche of
      the scoliotic girls was 11,98 years, SD 1,49 years, range 7,7 to 16,72 years.
      Twenty-eight scoliotic girls had no menarche yet (mean age 10.99 years, range
      7.41 to 17.24 years, SD=2.72). There was a predominance of right-sided primary
      curves in menarche positive scoliotic girls (61%), while menarche negative
      scoliotic girls showed mainly left sided primary curves (64,3%). This difference
      is statistically significant (p<0,05). The frequency of the various scoliotic
      curves in menarche positive scoliotic girls was as follows: right thoracic
      (32,5%), left lumbar (23,4%) and right thoracolumbar (15,6%) curves. The
      respective locations of scoliotic curves in girls without menarche were left
      lumbar (25%), left thoracolumbar (25%) and thoracic curves (14,3%) were equally
      distributed on both. Delayed onset of menarche or no menarche was observed in 4
      scoliotic girls. Furthermore, 2 scoliotic girls mentioned that they had menarche
      after the age of 15 years and only after hormonal treatment. Despite of the
      apparent prevalence of the scoliotic girls in the menarche positive population,
      there is no statistically significant difference between scoliotic and
      nonscoliotic girls with menarche when the respective ages at menarche are
      compared. CONCLUSION: In this study, there was not a statistically significant
      difference of the age at menarche between scoliotic and nonscoliotic girls. On
      the other hand, there was a significant difference between menarche positive and
      menarche negative scoliotic girls in relation to the laterality of scoliotic
      curves: the former showed predominantly right sided primary curves while the
      latter had mainly left sided primary curves.

PMID- 15456002
TI  - A statistical analysis of the familial incidence of Idiopathic Scoliosis.

PMID- 15456003
TI  - The Double Rib Contour Sign (DRCS) in lateral spinal radiographs: aetiologic
      implications for scoliosis.
AB  - All lateral spinal radiographs in idiopathic scoliosis show a DRC sign of the
      thoracic cage, a radiographic expression of the rib hump. The outline of the
      convex overlies the contour of the concave ribs. The aim of this study is to
      assess this DRC sign in children with and without Late Onset Idiopathic Scoliosis
      (LOIS) with 10 degrees -20 degrees Cobb angle, and to examine whether in
      scoliosis the deformity of the thorax or that of the spine develops first.
      METHODS AND MATERIAL: The radiographs of 133 children referred to hospital in a
      school screening study were examined. There were 47 boys and 86 girls, 13.28 and
      13.39 years old respectively. The Cobb angle was measured and the radiological
      lateral spinal profile (LSP) was appraised from an angle made by a line drawn
      down the posterior surface of each vertebral body (T1-L5) and by the vertical.
      The children, boys and girls, were divided in 5 groups, namely: 1) with straight
      spines, 2) with spinal curvature having a Cobb angle <10 degrees, 3) with
      thoracic, 4) thoracolumbar and 4) lumbar curves 10 degrees -20 degrees. For
      quantification of the DRC sign, the "rib index" was defined as d1/d2 ratio, where
      dl expresses the distance from the most extended point of the most projecting rib
      contour (RC) to the posterior margin of the corresponding to point vertebra and
      d2 expresses the distance from the posterior margin of the same vertebra to the
      most protruding point of the least projecting RC. In a symmetric and non-deformed
      thorax, these two RC lines are superimposed and the "rib index" is 1. RESULTS:
      The statistical descriptive of d1 and d2 in boys and girls are presented together
      because they are not statistically different. There are no sex differences of the
      "rib index" which is 1.45, 1.51, 1.56, 1.59, 1.47 for the 5 respectively
      aforementioned groups. According to statistical analysis, there is no correlation
      of the Cobb angle with the "rib index" of thoracic, thoracolumbar and lumbar
      scoliosis groups. The DRC sign is present in all referrals and scoliotics. The
      data show a correlation of the "rib index" with each of T2, T3, T4, T5, T6 and T7
      LSP in girls with lumbar curvatures. DISCUSSION: The DRCS primarily appears
      because of the rib deformation and secondarily because of the vertebral rotation,
      as it could be present in straight spines with no vertebral rotation. In all our
      school-screening referrals, (having ATI > or = 7 degrees), the thorax deformity,
      in terms of the DRC sign, has already been developed. 70% of these children were
      scoliotic. The others had a curvature of less than 9 degrees of Cobb angle (10%)
      or they were children with straight spines (20%) who were followed because of
      their existing rib hump. The non-scoliotics were 1,5-2 years younger than the
      ones who had already developed scoliosis, and they had both approximately a "rib
      index" of 1,5. The DRC sign is present in all referrals. In contrary, there is no
      scoliotic spine without it, as the DRC sign is always present in scoliotic
      lateral spinal radiographs with no exception. This observation supports our
      hypothesis that in idiopathic scoliosis, the deformity of the thorax develops
      first and then the deformity of the spine follows.

PMID- 15456004
TI  - Surface topography and the several components of scoliotic deformity.
AB  - Using previously established values for the smallest detectable difference in
      topographic parameters, the effectiveness of the Quantec system for monitoring
      progress in scoliosis was investigated. It was found that, while a significant
      change in Cobb angle was always accompanied by a meaningful change in at least
      one topographic parameter, the pattern of shape change was highly individual. It
      is concluded that deformity in scoliosis is not determined exclusively by the
      spinal curve.

PMID- 15456005
TI  - SYDESCO: a laser-video scanner for 3D scoliosis evaluations.
AB  - SYDESCO is a new 3D vision system developed for trunk surface topography. This
      structured light surface scanner uses the principle of triangulation-based range
      sensing to infer 3D shape. The complete trunk acquisition is fast (2 seconds).
      The accuracy of the metric data is ensured by a subpixel image detection and a
      calibration process, which rectifies image deformations. A preliminary study
      presents results on 50 children in a gymnastics school. These children, aged
      between eight to sixteen years, are particularly exposed to spinal deformities.
      An asymmetry index is calculated from the 3D data to detect the pathologic cases.
      These results have been compared to an independent medical diagnosis. The system
      results have been confirmed for 72,1% of the patients.

PMID- 15456006
TI  - The early detection of adolescent idiopathic scoliosis in three positions using
      the scoliometer and real-time ultrasound: should the prone position also be used?
AB  - The standing forward bending position is in general use for the early detection
      of adolescent idiopathic scoliosis. It also reveals humps caused by leg-length
      inequality and for this reason some workers have advocated using the sitting
      forward bending position. Most recently the prone position has been evaluated and
      even recommended. The introduction of B-mode and subsequently real-time
      ultrasound to measure rib rotation and spinal rotation has involved using the
      prone position. The numerical description of back humps in scientific studies
      requires measurements at several levels on the back from T1-S1. This paper
      utilizes 30 subjects referred by school screening for scoliosis from whom 10
      level Scoliometer Angle of Trunk Inclinations (ATIs) were obtained twice in each
      of three positions--standing forward bending, sitting forward bending and prone.
      The ATIs were converted to 18 levels and (1) analysed for reproducibility, (2)
      compared in the three positions, and (3) compared with real-time ultrasound data
      of rib rotation obtained in the prone position. Several statistical methods are
      used. The reproducibility is best in the sitting and prone positions. While the
      prone position produces lower ATI readings, R squared values are significantly
      higher and Residual Mean Square (RMS) values significantly lower than those for
      each of the standing and sitting forward bending positions. Though the prone
      position has clear advantages, it is not advocated in clinical practice for
      various reasons. More research is needed. The evidence supports the view that the
      sitting forward bending position has advantages for the early detection of
      adolescent idiopathic scoliosis.

PMID- 15456007
TI  - 3D back shape in normal young adults.
AB  - In today's climate of evidence based medicine, there is an increasing emphasis on
      objective assessment to monitor treatment effectiveness. Although spinal posture
      and back shape are commonly assessed by clinicians, current practice is based on
      subjective findings and unreliable objective tools. Numerous management protocols
      aim to improve both posture and shape, however data related to normal back shape
      is quite scarce. The aim of this study was to investigate normal back shape in
      young adults, in order to produce normative values against which deformity could
      be defined. The Integrated Shape Imaging System (ISIS) was used to measure the
      three-dimensional back shape. A convenience sample of 48 normal adults, aged 18
      28 volunteered to participate in this study. A small minority of individuals
      showed no curve (8%), 55% showed a single curve and the rest showed a double one.
      Right spinal asymmetry was more frequent than the left (77% to 52%). Mean values
      and 95% confidence intervals were 14.1 degrees (11.7 degrees-16.5 degrees) for
      upper Lateral asymmetry, 5.6 degrees (3.3 degrees - 7.9 degrees) for lower
      lateral asymmetry, 24.9mm (20.6mm -29.2mm) for thoracic kyphosis and 14.9mm
      (12.5mm -17.2mm) for lumbar lordosis. Increasing upper lateral asymmetry
      correlated with decreasing thoracic kyphosis (p=0.01). Maximum skin surface angle
      correlated positively with only upper lateral asymmetry (p<0.0001). Similar
      topographical interrelationships have been demonstrated in scoliosis. It is
      important that clinicians in relevant disciplines objectively assess all three
      dimensions of back shape, as our research shows that changes in one plane are
      associated with changes in the other two planes.

PMID- 15456008
TI  - 3-D back surface analysis of severe idiopathic scoliosis by rasterstereography:
      comparison of rasterstereographic and digitized radiometric data.
AB  - Rasterstereography has been shown to be a reliable method for three-dimensional
      surface measurement of idiopathic scoliosis with Cobb angles up to 50 degrees. In
      this study, 25 patients with severe idiopathic scolioses (Cobb angles 47 degrees
      92 degrees) were examined before and after operation (VDS instrumentation). The
      a.p. radiographs were digitized according to the Drerup method. The similarity of
      rasterstereographic and radiometric data was quantified by the rms. differences
      between the rasterstereographic and radiographic curves of lateral deviation and
      vertebral or surface rotation. The average rms. differences were 5.8 mm for
      lateral deviation and 4.4 degrees for vertebral and surface rotation, which is
      about 40% higher than for mild to medium scolioses.

PMID- 15456009
TI  - Evaluation of a laser scanner for surface topography.
AB  - A Minolta VIVID 700 portable non-contact 3D laser scanner was evaluated on 15
      subjects with idiopathic scoliosis. The 3D map was compared to two structured
      light pattern (lines and dots) techniques to determine the reliability, ease of
      use, speed, and quality. The parameters used for the clinical assessment of
      scoliosis were measured twice for the Minolta and light projection systems. The
      edges of the image and areas where occlusion typically occur were examined. The
      absolute distance in calculated depth between adjacent points was examined to
      determine errors. The Minolta system and the dot pattern produced regular grids
      of points. The light projection pattern produced an irregular grid, with more
      resolution along the video line and less resolution between projected lines,
      resulted in a somewhat jagged appearance of the surface map. The Minolta system
      was less sensitive to edge effects, occlusion, and sharp transitions of depth.
      The comparison of clinical parameters showed good results between repetitions but
      moderate results between techniques.

PMID- 15456010
TI  - Examination of relative movement between the back and lower limb.
AB  - The importance of trunk movement in human gait has been established by many
      studies. However, these investigations have examined trunk/pelvis motion or the
      pelvic/thoracic motion in isolation to lower limb kinematics. Studies quantifying
      spinal deformities and the range of spinal and trunkal movement have concentrated
      on spinal/back movement, with the subject performing tasks, such as flexion,
      while maintaining a static position. There is also a paucity of data detailing
      the real relative motion between the back and lower limb during gait, an
      important consideration when testing the Nottingham 'flag-pole' hypothesis for
      spinal curvature generation. Research into the use of opto-electronic gait
      analysis systems to measure dynamic back movements has shown the capability of
      these systems in producing repeatable patterns of back movements. While using a
      motion analysis system, if a relationship between the spinal movement and lower
      limb kinematics could be established, such a relationship would provide a new
      opportunity for range of movement studies in conditions like scoliosis.
      Furthermore, establishing such a relationship would allow investigation into the
      influence of one segment over another during locomotion. This present study has
      examined the movement of markers placed on the back and pelvis, used in three
      dimensional opto-electronic systems for gait studies, in relation to the markers
      placed on the lower limbs. The results of a pilot study have highlighted relative
      movements between various segments in simple tasks like flexion, lateral bending
      and negotiating steps, which have implications for spinal deformity generation.
      The findings also demonstrate the points to be considered in order to define
      dynamic trunk and spinal movement. Further ongoing studies are being undertaken
      to validate the findings.

PMID- 15456011
TI  - 3-D measurement of posture and back shape using a low cost, portable system--a
      reliability study.
AB  - The reliability and accuracy in the measurement of landmark points using a 3-D
      digitizer on a static back phantom are reported. The results show the systems
      clinical reliability as a low cost, portable and flexible method for recording
      back posture. Consistent results are demonstrated for a single measurer and good
      agreement was found between two measurers. Few intrinsic errors were found in the
      devices performance.

PMID- 15456012
TI  - Study of marker placements in the back for opto-electronic motion analysis.
AB  - Various investigations into anatomical landmarks that could be employed in spine
      and back surface measurement have highlighted the usefulness of the spinous
      processes of the vertebra and the posterior superior iliac spines of the pelvis.
      Earlier studies used an opto-electronic gait analysis system to examine the
      motion of skin markers and compared results with similar inter-vertebral movement
      recorded through radiographs. Consistent patterns of movement suggested a
      relationship between spinal and back surface motion. Further investigations into
      the use of opto-electronic gait analysis systems to measure dynamic back
      movements showed the capability of producing repeatable patterns of back
      movements. However, these studies, mainly measuring the range of movement (ROM)
      of spine, have not examined the effects of marker placements. While most ROM
      studies concentrate on stationary repetitive flexion/extension and bending
      movements, spinal ROM during walking and in scoliosis has not been widely
      reported. Spinal range of motion is an important indicator of spinal function and
      is used in the determination of disability and compensation. The present study
      has evaluated the placement of markers on the back and pelvis, used in three
      dimensional opto-electronic systems for gait and movement studies. Various marker
      configurations have been compared and reported. The findings highlight the
      drawbacks of previously reported techniques, and particularly indicate that skin
      movement can adversely affect findings. However, the results confirm the
      feasibility of application of this technique to investigate dynamic trunk and
      spinal movement in both normal and deformed spines.

PMID- 15456013
TI  - User friendly computer profilometry.
AB  - Portable optical profilometer for measurement and analysis of the human back
      shape has been developed. The driving user friendly software includes correction
      of distortion of the observation lens, data calibration, three-dimensional Z-axis
      rotation of the patient normalizing his position, calculus of the curvature map
      (second derivative), and precise indication of different characteristic points of
      the back including the spinous processes line. This instrument enables the
      examination of the back in both erected and bent positions.

PMID- 15456014
TI  - Surgery is performed for cosmetic reasons.

PMID- 15456015
TI  - Surgery is performed for functional improvements.

PMID- 15456016
TI  - Evaluation of the efficiency of patient stabilization devices for 3D X-ray
      reconstruction of the spine and rib cage.
AB  - Four devices designed to stabilize the patient's position and/or posture between
      X-ray exposures were investigated in order to obtain accurate 3-D reconstruction
      of their spine: a pelvis support, two elbow supports with handlebars, a back neck
      contact system and a device with three divergent laser beams pointing on subject
      body targets. Stability and the bearing of natural posture on a group of 10
      adults without scoliosis was evaluated for the different devices using a
      statistical experimental design (Plackett-Burman plan of resolution IV). Small
      displacements of subjects were obtained by an Optotrak system with 11 infrared
      diodes placed on the subject's back. Results showed that the elbow supports with
      handlebars and pelvis support improved the subject's stability while the pelvis
      support was the device that produces more changes in the subject's natural
      posture. The elbow and back neck supports were retained for further evaluation.

PMID- 15456017
TI  - Semi-automatic landmark detection in digital X-ray images of the spine.
AB  - Quantitative diagnosis of 3D scoliotic deformities depends on a number of
      dedicated measurements. Existing methods rely on the manual determination of a
      series of anatomical landmarks in X-ray images. We have developed an automatic
      method to alleviate the burden of this tedious task. Our method looks for a
      compromise between local image information and global prior constraints and finds
      the most probable points using dynamic programming optimization. Remaining errors
      can be quickly corrected by effective user interaction. The first results are
      promising.

PMID- 15456018
TI  - Does transverse apex coincide with coronal apex levels (regional or global) in
      adolescent idiopathic scoliosis?

PMID- 15456019
TI  - Correlation study between indices describing the scoliotic spine.
AB  - This study intended to investigate the correlations between different geometrical
      indices in order to assess their usefulness in the characterization of scoliotic
      deformities. Analytical evaluation of indices was obtained from 3D reconstruction
      of vertebrae. Scoliotic indices included the Cobb angle, the Cobb angle in the
      plane of maximum curvature, the angular orientation of the plane of maximum
      curvature, the kyphosis and the maximal axial rotation. This analysis was applied
      to the thoracic curve of 100 scoliotic adolescents. The correlations between
      these five indices were separately investigated for the RT and RTLL curve types.
      A statistical correlation was found between the angular orientation of the plane
      of maximum curvature and the kyphosis. The results indicate a relative
      independence between most indices. Hence, an evaluation of several complementary
      indices is required to provide a more complete description of 3D scoliotic
      deformities.

PMID- 15456020
TI  - Simplified calibration system for stereoradiography in scoliosis.
AB  - Stereoradiography is a well known method to obtain 3D images of the spine and the
      thorax. The main algorithm used is the DLT, which is a very general one yielding
      to 11 implicit parameters per view. In order to calibrate the geometrical
      configuration of the stereoradiographic setup with this algorithm, there is a
      need of a wide calibrating object, leading to systems hard to use in clinical
      practice. The aim of this work was to modify the algorithm in order to simplify
      the calibration object. We used assumptions related to the specific case of
      stereoradiography, which reduced the problem of calibration to only 6 independent
      explicit parameters. A geometrical calibration performed plane by plane enabled
      to design a singular calibration object composed of steel balls along two
      vertical lines and three horizontal ones. A simulation of real configuration both
      for the previous method and the current algorithm associated to the singular
      calibrating object give for thirty 3D points a 2 RMS (95% confidence interval)
      error of reconstruction of respectively 0.6 and 0.3 mm. This study yielded to the
      transfer in clinics of two simplified systems of calibration which will be easier
      to use in clinical practice.

PMID- 15456021
TI  - Rule-based algorithm for automated King-type classification of idiopathic
      scoliosis.
AB  - Recent studies have demonstrated poor reliability of the King et al.
      classification of idiopathic scoliosis. The purpose of the present work was to
      determine whether the reliability of the King classification would be improved by
      employing unambiguous rules for classification encoded in a computer program.
      Thus the only possible source of variability in classifying a given radiograph
      would be variable landmark identification on the radiograph. Coordinates of the
      four comers of each thoracic and lumbar vertebra were obtained by digitizing
      radiographs, using the central sacral line to define the y-axis. A computer
      algorithm located curve apices as the most laterally deviated vertebra in a range
      of two above to two below a change in the sign of vertebral tilt. End vertebrae
      of each curve were located as those with the greatest tilt of the superior
      (proximal end vertebra) or inferior (distal end vertebra). In a lumbar curve, the
      apical vertebra was defined as 'crossing the midline' if all four corners laid on
      one side of the vertical central sacral line. Curves were defined as in Table I
      in King et al., except that curve flexibility data were not used. The algorithm
      was verified on the five examples in King et al. It then classified the six
      examples in Lenke et al. and Cummings et al. which were classified unreliably by
      human observers. The algorithm was also tested on 33 radiographs of 17 patients
      with AIS, 8 radiographs were repeat marked by two observers. The algorithm
      overcame accuracy and reliability problems, except in rare cases when it was
      borderline whether or not a lumbar curve crossed the midline, when the apex level
      was ambiguous, or when a Cobb angle was close to 10 degrees.

PMID- 15456022
TI  - Augmented reality in spine surgery: critical appraisal and status of development.
AB  - In spinal surgery, computer assistance in the operating room is gaining fast
      paced acceptance, but it would be simplistic to imagine that added technology is
      systematically beneficial to the patient. As surgeons are not experts in computer
      technology, there is a tendency to abandon the evaluation to the market and say
      the best will emerge. Based on our experience with the development of our own
      system and confronted with the emergence of new systems adopting solutions we had
      rejected, we propose a framework to compare various systems between them. Similar
      evaluation protocols are in use for surgical implants, the same should be done
      for computer assistance.

PMID- 15456023
TI  - The orientation of the plane of maximum deformity of a scoliotic curve.

PMID- 15456024
TI  - Modelling and analysis of vertebra deformations with spherical harmonics.
AB  - In this paper we present an elaborate and precise geometrical model of the spine
      structure based on spherical harmonics. We first describe the application of
      spherical harmonics to the modelling of the vertebra surface, then we study the
      behaviour of the model under particular deformations. The first results of this
      study show that we can obtain a realistic model of each vertebra of the spine and
      that it is possible to estimate particular deformations with a good accuracy from
      the spherical harmonics coefficients of the deformed surface. Furthermore, this
      model constitutes an a priori geometrical knowledge for the diagnosis of the
      spine scoliosis in a three-dimensional approach (reconstruction from 2D images).

PMID- 15456025
TI  - Validation of the NSCP technique on scoliotic vertebrae.
AB  - The purpose of the present study is to validate a quite recent stereoradiographic
      3D reconstruction technique, called Non Stereo Corresponding Points (NSCP), on
      scoliotic patients. The validation of the NSCP technique on scoliotic patients
      was performed on 59 scoliotic vertebrae from 14 patients, by comparison to the CT
      scan. The results of this study show mean errors of 1.5 mm. These results should
      still be optimized for the geometrical modelling. Nevertheless, this technique
      may already be used as a diagnosis tool in clinics.

PMID- 15456026
TI  - 3D reconstruction and analysis of the vertebral body line.
AB  - Quantitative analysis of 3D spinal deformities includes measurements related to
      individual vertebrae and measurements related to the overall shape of the spine.
      For the latter aspect, we propose to build a 3D model of the line that connects
      all vertebrae centres. We present two methods that allow reconstructing this
      vertebral body line in a quick and easy way. Various new descriptors of the
      spinal shape can be automatically computed. A study is under way to assess their
      clinical relevance and reliability.

PMID- 15456027
TI  - 3D reconstruction of the pelvis using the NSCP technique.
AB  - Many authors have already pointed out the importance of the three dimensional
      aspect when dealing with pelvic and spinal pathologies. The purpose of the
      present study is to verify the feasibility on the pelvis and the accuracy of a
      recent 3D reconstruction technique based on biplanar X Rays with regard to direct
      measurements. The results on 8 dry non-pathologic pelvises show a mean error of
      3.9 mm for the global geometry of the pelvis, with local maxima of 26 mm and 95%
      of errors inferior to 14.5 mm.

PMID- 15456028
TI  - Automatic measurement of scapula position and movement using rasterstereography.

PMID- 15456029
TI  - Image coding technique for 3-D back reconstruction.
AB  - This work investigated the use of coded-line patterns to improve image
      correspondence and 3D reconstruction. The objective was to define an optimum
      structured light pattern to facilitate the construction of topographic maps of
      the trunks of scoliosis patients. The system consisted of stereo CCD television
      cameras, a slide projector to create the coded-line pattern and a computer with
      video acquisition card. The optimum pattern in terms of generating correct
      results with minimum computing time was a line pattern consisting of 6 groupings
      of 3-level grey lines. This chosen pattern was investigated using known 3D
      objects to determine the effectiveness, resolution and computational time to
      correlate stereo images. The selected structured light pattern consisted of a
      repeated pattern of white (W), grey (G) and black (B) lines. Each line was 4mm
      wide on the back surface. The pattern consisted of 6 groups of 3 lines, WBG WGB
      GWB GBW BGW BWG. Using known 3D models of a section of a cylinder, a plate with
      steps and a ramp-like object; the coded line system was tested under typical
      clinical lighting conditions. For the 3D test objects, errors in correspondence
      occurred in 2-4 % of stereo pixels. The processing time varied from 10-12
      minutes. The 3D resolution obtained was 4mm.

PMID- 15456030
TI  - Ultra low dose X-ray spinal examinations.
AB  - The study and treatment of spinal deformities may lead to excessive doses of
      radiation for patients (especially children) examined by conventional X-ray
      radiology apparatus. In order to avoid this very crucial problem, a new X-ray
      radiology system has been devised. The new apparatus uses a high efficiency
      linear solid-state detector and highly sensitive electronics, operating in single
      X-ray counting mode (quantum mode). The scan parameters and image filtering are
      computer controlled. Data is acquired in real time by a high speed VME system. In
      this paper, the first images recorded using this new apparatus are shown. The
      main conclusion of the preliminary comparative dosimetric analysis is that it is
      possible to divide the patient's dose by a factor of at least ten to one hundred
      with the quantum X-ray radiology apparatus.

PMID- 15456031
TI  - Comparison of rasterstereographs with MR scans in scoliotic patients.

PMID- 15456032
TI  - 3D location of the rib prominence and its importance in the treatment of
      scoliotic deformities.

PMID- 15456033
TI  - Relationships between strap tension, interface pressures and spine correction in
      brace treatment of scoliosis.
AB  - The Boston brace has been shown to efficiently prevent scoliosis curve
      progression. However, it rarely achieves complete 3-D correction; its adjustment
      being often empirical and its biomechanical modes of action still remaining
      poorly understood. This study investigates the in-brace spinal shape (correction)
      in relationship with the patient's out-of-brace deformation, and the adjustment
      parameters of the brace, namely the strap tensions and the equivalent forces
      calculated at the patient-brace interface. Many of the observed relationships
      illustrate the fact that the in-brace spinal shape is strongly related to the
      characteristics of the patient's out-of-brace deformation. The pattern of
      pressure distribution as described by the equivalent forces computed in the
      thoracic, lumbar, pelvic and sternal regions has important effect on the in-brace
      Cobb angles, lumbar lordosis, frontal and sagittal imbalances and the apical
      axial rotations. The complex role of the strap tension on the correction has not
      been explained and needs further investigation. This project has the potential to
      give insight into the biomechanical effects of brace treatment by providing a
      statistical model leading to more rational and personalized brace adjustments.

PMID- 15456034
TI  - Monitoring of side shift exercise using an electromagnetic three-dimensional
      measuring device.
AB  - In order to investigate the usefulness of an electromagnetic three-dimensional
      measuring device as a monitor for the side shift exercise, the evaluation by the
      well-trained physical therapist as to whether the exercise was properly performed
      or not was compared with the evaluation using data obtained by the device. The
      side shift exercises performed by twenty-four female patients with idiopathic
      scoliosis were classified as "good," "rotation," or "bend" by the well-trained
      physical therapist. By the use of the data obtained by the electromagnetic three
      dimensional measuring device, whether the exercise was "rotation" or not could be
      predicted with 100% sensitivity and 100% specificity, and whether the exercise
      was "bend" or not could be predicted with 83% sensitivity and 100% specificity.
      These results suggested that the electromagnetic three-dimensional measuring
      device could be a useful monitor for the side shift exercise.

PMID- 15456035
TI  - SPINECOR: a new therapeutic approach for idiopathic scoliosis.

PMID- 15456036
TI  - Brace monitoring system for the treatment of scoliosis.
AB  - Determining the efficacy of brace treatment for AIS has been hampered by poor
      data on the wear pattern of those children prescribed this treatment. Although
      there is some information on brace compliance, there is very little on how well
      the brace is secured and the resulting loads imposed on the trunk. The purpose of
      this study was to determine the daily brace wear pattern of adolescents
      prescribed Boston braces. The brace monitoring system consists of a force
      transducer and a microcomputer unit. A force transducer was placed in the lining
      of the Boston brace. The microcomputer unit was carried while the brace was worn.
      The force imposed by the brace pad during daily activity was recorded at 1 minute
      intervals over a period of 3 to 14 days. The samples were stored by the
      microcomputer. Five subjects (3F;2M; age: 14+/-2 years) who were to wear the
      brace full time were studied. The subjects adjusted their braces to a prescribed
      level of tightness as indicated by a light on the microcomputer. Overall
      compliance, compliance during school days, and forces imposed by the brace were
      analysed. The force provided by the Boston brace varies considerably during daily
      activity. Overall brace compliance was lower than expected, with 2 of 5 subjects
      wearing their brace infrequently. The compliance rate during school time was not
      different than during the rest of the study period. Peer pressure at school did
      not appear to affect brace compliance.

PMID- 15456037
TI  - Adolescent idiopathic scoliosis: is the search for aetiology constrained by the
      orthosis?
AB  - While the aetiology of adolescent idiopathic scoliosis is unknown, it is widely
      believed that the deformity can be controlled by mechanical forces applied by a
      corset and acting, via skin and soft tissues, to exert pressure on vertebral
      growth-plates (Hueter-Volkmann Law). The reported efficacy of bracing in reducing
      the incidence of small degrees of progression reinforces this concept. The
      supposed mode of action conditioned the model of pathomechanism and precludes
      other hypotheses. Since the critical Cobb angle changes are usually less than the
      probable measurement error, another criterion (treatment outcome) is also
      relevant. At our centre, bracing for adolescent idiopathic scoliosis has not been
      practised for 9 years. Out of the 153 untreated, unselected patients presenting
      to the general scoliosis clinic in that time and who were at least 15 years old
      at the last review, 43 (27.6%) of them have undergone surgery. This does not
      differ statistically from 22.45% (229 of 1,020) braced patients reported by
      Lonstein and Winter in 1994. If bracing does not significantly improve prognosis,
      its efficacy cannot be accepted and the hypothesis of aetiology which it
      underpins has no greater standing than any other.

PMID- 15456038
TI  - Three-dimensional action of Cheneau brace on thoracolumbar scoliosis.
AB  - We treated 18 girls for idiopathic thoracolumbar scoliosis with Cheneau brace.
      The apex of the curve was at Th12 or at L1 or at the disc Th12/L1. The initial
      Cobb angle varied from 21 to 42 degrees, mean 28. The follow up period was of 2
      years and 6 months on the average. We noted the rib hump height on Adams' forward
      bending test. We measured Cobb angle, apical vertebra transposition and apical
      vertebra rotation (according to Perdriolle method) on antero-posterior standing
      radiograms before the treatment had started and at the moment of the best
      correction. We digitized antero-posterior and lateral standing radiograms with
      sonic digitizer GP-9 and we prepared computed reconstruction of the transversal
      plane of the spine with Hecquet and Graf's software RACHIS 91TM. The best
      clinical and radiological correction was achieved after 3 to 8 months of
      treatment (mean 5,5 months). We considered it as the fitting period and we
      analysed the correction achieved at that moment and at last follow-up. Cobb angle
      in brace ranged from 0 to 18 degrees, mean 9 degrees. The correction of apical
      vertebra transposition ranged from 51% to 100%, mean 80%. The correction of
      apical vertebra rotation ranged from 0% to 100%, mean 52%. The correction of rib
      hump ranged from 0 to 100%, mean 42%. Normal sagittal contour was established in
      15 patients. CONCLUSION: important correction was present in each of the three
      planes.

PMID- 15456039
TI  - CTM brace effect on scoliotic intervertebral discs using MRI method.
AB  - MRI has been clinically only used for investigation of intervertebral disc
      disorders. In this study, MR images were used and a new 3D modelling of the
      intervertebral discs was proposed. MRI examination had been performed on fourteen
      girls presenting an idiopathic scoliosis and wearing a first CTM brace. Using an
      in-house image processing software and the pre-post processing software Patran,
      geometrical models were obtained with and without brace for each patient. These
      models included the outline of the intervertebral high intensity zone, composed
      of the nucleus and a part of the annulus. The shift forward between disc high
      intensity zone centres and body centres was found to be varying from 0 to 8mm.
      The sagittal and coronal shifts forward appeared in the curvature convexity and
      were maximum at the curvature apex. The intervertebral disc wedging was found to
      be varying from -10 degrees to +10 degrees. On these fourteen analysed patients,
      the CTM brace decreased the coronal shift forward between disc high intensity
      zone centres and body centres, and increased the sagittal intervertebral wedging.
      The intervertebral disc informations obtained represented new data in the
      scoliotic deformation description. But this method was not adapted for a clinical
      use. The qualitative and quantitative data obtained will help the orthopaedist in
      the brace design and also the clinician in the scoliosis comprehension.

PMID- 15456040
TI  - 3D brace correction of spinal deformities in growing patients with severe forms
      of idiopathic scoliosis.

PMID- 15456041
TI  - Effect of bracing on postural balance in idiopathic scoliosis.

PMID- 15456042
TI  - Retrospective results in immature idiopathic scoliotic patients treated with a
      Cheneau brace.
AB  - This paper reports a retrospective series which includes 105 idiopathic scoliotic
      patients treated with a Cheneau brace. With an average age of 12.5 years old and
      a mean Risser sign of 0.9, the initial major Cobb angle was 36.8 degrees
      corrected to 25.9 degrees in the brace (31.1% of the primary correction), and the
      major torsion angle was 16.8 degrees corrected to 12.9 degrees in the brace
      (22.2% of the primary correction). 37 patients have finished the treatment with a
      mean follow-up of 16.8 months. For this group, the initial Cobb and torsion
      angles were not significantly changed (36.4 degrees Cobb to 34.1 degrees Cobb at
      follow-up, and 16.9 degrees Perdriolle to 15.7 degrees Perdriolle at follow-up).
      The proportion of patients without progression greater than 5 degrees Cobb (n=20)
      and with an improved final Cobb angle (n=10) was greater than failures (n=7).
      However, due to the catastrophic nature of some progressions which generally
      coincide with a high Cobb angle right from the start, with low primary
      correction, and with non-compliance, the final Cobb angle showed a slight
      tendency to decrease but without reaching high significance. These preliminary
      results demonstrate that the Cheneau brace can effectively prevent the
      progression of Cobb and torsion angles, even in cases of bad prognosis.

PMID- 15456043
TI  - Outcome of in-patient rehabilitation in patients with M. Scheuermann evaluated by
      surface topography.
AB  - For the follow-up of patients with sagittal spinal deformities and postural
      disorders, we do not have well validated measuring systems at our disposal. All
      clinical measuring parameters are liable to a high margin of error. With a
      growing number of patients suffering from postural disorders and kyphoses, we
      have to look for other possibilities to monitor changes of the back, as well as
      in the short term, without the support of X-rays. As the measuring of the surface
      with the Formetric system showed a high measurement reliability in previous
      studies, we used this system to demonstrate the rehabilitation results of our
      patients with Scheuermann's disease. An intervention study (pre-/post-design) was
      undertaken including the following material.: 62 female patients with
      Scheuermann's disease and an average age of 19 years old and 74 male patients
      with Scheuermann's disease and an average age of 20 years old were measured with
      the Formetric system before an in-patient rehabilitation of four to six weeks.
      For this study, we evaluated the maximal kyphotic angle as shown by the system.
      In the case of female patients, the maximal kyphotic angle decreased highly
      significantly from sixty two to nearly fifty four degrees. In the case of the
      male patients, it decreased from sixty to nearly fifty five degrees at the end.
      It showed that the surface measuring system with the Formetric System is a
      reliable instrument for the follow-up of sagittal postural disorders and kyphoses
      for the present study, especially in the case of Scheuermann's disease. In
      praxis, the use of this measurement is very easy, we obtain the measurement
      results very quickly, so that the evaluation of data is not very time consuming.
      After the in patient treatment, the kyphotic angle decreased highly
      significantly. The changes range far above the margin of error, thus the
      following conclusions are justified. Firstly, the Formetric System is the
      appropriated instrument for the follow-up of postural disorder and kyphoses.
      Secondly, the in-patient rehabilitation with an intensive treatment program may
      result in a correction of also structural kyphoses with sure signs of
      Scheuermann's disease. Thus we recommend an in-patient rehabilitation in
      adolescent age in case of Scheuermann kyphoses with large curvatures and in case
      of Scheuermann kyphoses in adults suffering from pain.

PMID- 15456044
TI  - Rehabilitation of scoliosis patients with pain after surgery.
AB  - In our centre, the postoperative scoliosis rehabilitation consists in stabilizing
      postural and respiratory exercises lasting several hours a day (5 1/2 to 7
      hours). Additionally to pain treatment, we apply pain physiotherapy, physical
      therapy, acupuncture and besides manual medicine, also a psychological
      intervention and pain treatment by medication. 46 patients suffered from heavier
      pain 10 or more years after scoliosis surgery. The patients reported their pain
      at the beginning and at the end of 3-6 week in-patient rehabilitation programme.
      We applied a visual analogous scale (VAS), a numerical scale (NS), a standardized
      adjective scale (VRS), and a pain frequency scale. All the patients with an
      average age of 36 years old (SD=16) and an average curve angle of 35 degrees
      thoracic (SD=36) and 26 degrees lumbar (SD=22) showed a decrease of the values on
      the pain intensity scale. Pain reduction was highly significant, as well as pain
      frequency. Chronic pain as a late result following scoliosis surgery can be
      reduced by an intensive in-patient rehabilitation, at least in the short term.
      There are further necessary studies in order to follow-up the long-term effect of
      postoperative rehabilitation.

PMID- 15456045
TI  - Effect of intensive rehabilitation on pain in patients with Scheuermann's
      disease.
AB  - In our rehabilitation centre, the treatment of Scheuermann's disease consists of
      a daily postural education, lasting several hours. As for pain therapy, we mainly
      apply physiotherapeutic methods with osteopathy, manual therapy, Mc Kenzie and
      Brugger. In addition, we offer psychological help for pain relief. In case of
      severe chronic pain, we additionally treat it with acupuncture. Pain therapy with
      medication is only performed in rare cases. The aim of the present study was to
      find out if such an intensive rehabilitation programme had any effect on pain
      level in patients with Scheuermann's disease. An Intervention study (pre-/post
      design) was undertaken including the following material: 351 patients suffering
      from Scheuermann's disease reported their pain level before and after an
      inpatient treatment. For this aim, we used a visual analog scale (VAS), a
      numerical scale (NS), a standardised adjective scale (VRS) and a pain frequency
      scale. In our group, there were 61 female patients with a thoracolumbar
      Scheuermann's disease, 121 female patients with a thoracic Scheuermann's disease,
      92 male patients with a thoracolumbar Scheuermann's disease and 77 male patients
      with a thoracic Scheuermann's disease. The average age was 17 to 21 years old
      with an average kyphotic angle varying in the individual groups between 53 and 64
      degrees. In the case of the numerical pain severity scale, pain severity was for
      example 2,9 in female patients with thoracolumbar Scheuermann's disease. In
      female patients with thoracic Scheuermann's disease, pain severity was also at
      2.9. In male patients with thoracolumbar Scheuermann's disease, it was at 2.0 and
      in male patients with thoracic Scheuermann's disease, it was at 1.9. This
      numerical pain scale showed highly significant changes in pain severity: 2.1 in
      female patients with thoracolumbar Scheuermann's disease, 1.9 in female patients
      with thoracic Scheuermann's disease, 1.4 in male patients with thoracolumbar
      Scheuermann's disease and 1.8 in male patients with thoracic Scheuermann's
      disease. There was also a significant decrease in pain frequency. Seen as a
      whole, each scale showed a pain reduction between 16 and 32%, which is
      significant in all the cases and even highly significant in some cases. The in
      patient rehabilitation seems to have a positive effect on pain level in patients
      with Scheuermann's disease. In case of Scheuermann's disease in adult age,
      treatment is only indicated when patients suffer from pain. For those reasons, an
      in-patient intensive program of rehabilitation in a clinic with adequate quality
      structure should be considered.

PMID- 15456046
TI  - Idiopathic scoliosis under 30 degrees in growing patients. A comparative study of
      the F.E.D. method and other conservative treatments.
AB  - PROBLEM ADDRESSED: Treatment of scoliosis under 30 degrees Cobb in growing
      patients remains controversial. Different orthopaedic devices have been developed
      and used with satisfactory results, alone or in combination with a variety of
      physiotherapy programs. The F.E.D. method is a dynamic three-dimensional therapy
      consisting in the application of derotational forces under spine stretching. This
      method offers some advantages over conventional conservative treatment for
      scoliosis: shorter treatment period, no use of plasters in many cases, better
      psychological tolerance, etc. PURPOSE OF THE WORK: In this work, the results of
      the F.E.D. method were compared to other conservative treatment techniques in
      scoliosis under 30 degrees Cobb angle and Risser 3 or less. RESEARCH METHOD: Both
      the F.E.D. group and the group of patients treated by traditional orthopaedic
      methods included 30 children. Patients were divided on the basis of the type of
      scoliotic deformity: thoracic, thoracolumbar or lumbar. SUMMARY OF RESULTS AND
      FINDINGS: The results obtained showed that patients treated with the F.E.D.
      method had a significantly better outcome than the other methods in terms of
      angle correction and shorter period of treatment necessary to reach correction.
      CONCLUSION: The F.E.D. method can be considered as the elective treatment in
      growing adolescents with scoliosis under 30 degrees.

PMID- 15456047
TI  - Benefits of F.E.D. treatment in Scheuermann's disease.
AB  - PROBLEM ADDRESSED: Scheuermann's disease or deforming vertebral osteochondritis
      affects about 5% of the population. These patients become permanent users of
      rehabilitation services due to their discomfort. In periods of acute pain
      patients can only receive palliative and not very effective treatment. PURPOSE OF
      THE WORK: In this study 30 patients who fulfil the criteria for diagnosis of
      Scheuermann's disease were treated with the F.E.D. device. By using this method,
      a back pressure of up to 100 kg can be applied at the apex of the kyphosis,
      stretching the anterior common vertebral ligament in an attempt to diminish
      complaint. RESEARCH METHOD: There were 14 men and 16 women with ages ranging from
      15 to 35 years old. The mean kyphotic angle was 53 degrees (range, 45-65).
      Patients had an average Risser of 4.75 (range, 3-5). Schober's test disclosed a
      range of values from 0 to 2.5 cm (mean, 0.78). The average period of treatment
      was 4 months (80 sessions of treatment). SUMMARY OF RESULTS AND FINDINGS: All the
      30 patients referred disappearance of thoracic back pain after treatment. This
      pain relief effect was permanent for the time of follow-up. Kyphotic angle
      decreased from a mean of 30 degrees Cobb to 45 degrees (16% correction). A home
      physiotherapy program was recommended to all the patients in order to maintain
      dorsal elasticity as measured by Schober's test. After treatment, the mean
      Schober test value was 2.92. In cases treated during the growing period, where
      alterations in the spine were minimal or did not show radiographic alterations,
      progression of the kyphotic deformity was stopped. CONCLUSION: The F.E.D. device
      has shown to be a promising method both for the treatment of complaints in
      stabilised Scheuermann's disease and control of the progression of kyphotic
      deformity in the growing spine.

PMID- 15456048
TI  - Radioaerosol lung scintigraphy in idiopathic scoliosis.

PMID- 15456049
TI  - Scoliosis and leg asymmetries: a reliable approach to assess wedge solutions
      efficacy.
AB  - The aetiological aspects as well as postural attitude implications represent an
      open question in the evaluation and in the treatment to be applied in scoliosis.
      Legs asymmetry is often recognized in scoliotic patients, but still controversial
      is the use of underfoot wedges in order to compensate pelvis tilt. This could be
      due to the great uncertainty and intrinsic error level of the traditional
      clinical and visual measurements methods that present limitations in the
      assessment of all the 3D involved postural and morphological parameters. This is
      especially true given the clinical difficulty in the estimation of pelvic torsion
      usually coupled to leg asymmetry. In such a topic, a significant helpful tool has
      been demonstrated to be the opto-electronic measurement approach proposed by
      D'Amico et al., particularly given the innocuousness of the analysis and the
      speed of the clinical parameter extraction procedure. The present investigation
      demonstrates on a sample of 220 patients the efficacy of under-foot wedge use in
      leg asymmetry correction, posture re-balancing and spine deformities reduction,
      pointing out the significant contribution of the 3D opto-electronic measurement
      approach in the critical process of assessing the correct under-foot wedge size,
      therapy monitoring and follow-up.

PMID- 15456050
TI  - Treatment of chronic pain in adult scoliosis.
AB  - INTRODUCTION: One of the most important sequels of scoliosis in adults is pain,
      caused either by muscular overuse and imbalance or by nerve root compression.
      This is a very difficult sequel to treat because of the failure of the common
      analgesic drugs and physiotherapy treatments. MATERIAL AND METHOD: We studied 30
      patients with degenerative scoliosis of different origins. There were 24 women
      and 6 men. Patient age ranged from 25 to 55 years old. The initial Cobb angle
      ranged from 25 degrees to 65 degrees with a mean of 35 degrees. The mean Schober
      back score* at the beginning of treatment was 1.32. The number of sessions with
      the F.E.D. method were between 20 and 60 with a mean of 45 sessions. All the
      patients had a case history of NSAIDs, muscle relaxants and physiotherapy.
      RESULTS: The final average Cobb angle was 33 degrees and Schober score* 2.88.
      After treatment, only two cases required NSAIDs, muscle relaxants and
      physiotherapy. CONCLUSIONS: The F.E.D. method seems to be a promising alternative
      for treatment of painful sequels in adult scoliosis, since in our study
      disappearance of symptomatology was seen in the majority of cases. The F.E.D.
      method also had a permanent effect over time if patients followed a home
      physiotherapy program. This analgesic effect has a direct relation with the
      improvement achieved in the flexibility index.

PMID- 15456051
TI  - Application of passive transverse forces in the rehabilitation of spinal
      deformities: a randomized controlled study.
AB  - In our centre, physiotherapy and braces are the main approaches in the management
      of scoliosis and kyphosis as well. If a surgical intervention is necessary
      patients are guided to the appropriate centre for spine surgery. In order to
      avoid surgery, we are looking for possibilities to improve the conservative
      facilities of spinal deformities management. The aim of our study was to find out
      whether the use of passive transverse forces (PTF) applied on the deformed body
      is useful in the rehabilitation process of patients with spinal deformities. A
      randomized controlled study was undertaken including 126 patients with scoliosis
      treated with our intensive rehabilitation programme and 4 to 6 PTF treatments
      lasting 20 minutes per treatment. This group had a curvature angle of 38,7
      degrees (SD 16,8) thoracic and 32 degrees (SD15,1) lumbar. Average age was 14,8
      years (SD2,7). The control group of 126 patients had a curvature angle of 33,1
      degrees (SD 16,1) thoracic and 26,9 degrees (SD12,7) lumbar. Average age was 15,2
      years (SD2,3). The patients were randomized by the third author in order to have
      inpatient rehabilitation and PTF or intensive inpatient rehabilitation alone. For
      the result evaluation we carried out an investigation before and after the
      intensive inpatient rehabilitation phase of 4-6 weeks long with the surface
      measuring system (Formetric system). We evaluated the average lateral deviation
      value, measured in mm, as given out by the system. The value of average lateral
      deviation in the treatment group decreased highly significantly (p=.00157) with
      an average improvement of 1.27 mm. The controls also improved comparing the value
      for the average lateral deviation before and after rehabilitation with an average
      difference of 0.94 mm, which was not significant in the T-test (p=0.10032). When
      comparing the treatment group (PTF) without additional braces (n=52) the
      difference was even bigger with 1.50 mm (p=.0307). The control group without
      brace showed similar results as the entire control group. Only uncorrected
      posture can be measured with the Formetric system. When trying to show the
      possible postural corrections with the help of the Formetric system, more than
      50% of the scans show artefacts resulting from the fact that the points necessary
      for calculating the spinal deviation can no longer be automatically recognized.
      For this reason also the changes after an intensive inpatient rehabilitation are
      very moderate, even if they show a significant tendency to postural correction in
      larger groups. In smaller groups however, we generally only find the
      nonsignificant tendency to postural correction. Significant values were obtained
      with additional application of the PTF treatment. This proves the efficacy of
      passive forces combined with intensive physiotherapy aiming at an active
      stabilization of the passively mobilized spine. The uncorrected posture is
      improved significantly by inpatient rehabilitation and PTF, thus the treatment of
      scoliotic patients with the described methods is superior to inpatient
      rehabilitation alone.

PMID- 15456052
TI  - Biology is the future of scoliosis treatment.

PMID- 15456053
TI  - Minimally invasive surgery is so far the key to scoliosis treatment.

PMID- 15456054
TI  - Muscular modelling: relationship between postural default and spine overloading.
AB  - The objectives of the study are to describe and use a muscular model to compare
      spinal loads and muscles recruitments between an unbalanced subject (patient) and
      a normal volunteer. Data collection was performed and imputed into the muscular
      model: from sagittal X-rays, together with plantar foot pressure measurements,
      external loads for the L3/L4 level were calculated. Using MRI of the thoraco
      lumbar region and muscular testing, a personalized muscular model was
      constructed. The main results are as follow: external loads for the unbalanced
      subject were higher because of the postural default, especially for flexion
      moment. Running the model, simulations showed a higher erector spinae group
      activation for the patient. This induced a significant difference in joint
      compression. Setting the maximum admissible stress of the extensor muscles of the
      patient to an equivalent level as the one found for the volunteer to maintain the
      posture, a second simulation was performed. Joint compression was reduced, but
      postero-anterior shear and flexion moment increased drastically. The model
      suggests that either the muscular system needed a stronger activation, yielding a
      higher joint compression and probably a muscle fatigue in such an activation
      level, or the spinal loads increased to a higher and probably dangerous level.

PMID- 15456055
TI  - Intra-operative measurement of vertebral bone strength.
AB  - A significant complication of surgical correction of the deformed spine is pull
      out of the vertebral hooks or screws. This complication can be partly attributed
      to poor bone stock. Currently, there are few methods available for surgeons to
      assess the mechanical strength and stiffness of the vertebra, and even fewer
      methods that provide in-vivo measurements. An "upbiter" is often used to form a
      seat in the lamina for the hook. A typical upbiter was modified and instrumented
      with strain gauges to investigate the feasibility of determining the forces and
      displacements needed to cut through laminar bone during surgical procedures. The
      calibration showed that the system was repeatable and could highly correlated
      with applied force (R2=0.98) and displacement (R2=0.99) with resolutions of 0.72
      N and 0.40 mm respectively. This system was tested on three females, on lamina
      ranging from T4 to T12 regions. The average maximum force for bone failure was at
      470+/-128N.

PMID- 15456056
TI  - Investigation of muscle recruitment patterns in scoliosis using a biomechanical
      finite element model.
AB  - The objective of this project is to study the characteristics of trunk muscle
      recruitment strategies experimentally observed for scoliotic subjects using a
      finite element model of the trunk. The personalized biomechanical model includes
      elements representing the osseo-ligamentous structures of the spine, rib cage and
      pelvis. It also integrates the principal agonistic muscles necessary for trunk
      movement and a neural control model based on the Equilibrium Point hypothesis
      (lambda model of Feldman). Muscle recruitment patterns of normal and scoliotic
      subjects obtained from the simulation of lateral bending movements were
      qualitatively compared. The generation process of motor control variables was
      studied by analysing the relationships between central commands and spine segment
      mobility. Differences in recruitment patterns between normal and scoliotic
      subjects were observed, especially for paraspinal fascicles crossing the thoracic
      curve segment. The generation of central commands for normal subjects was
      strongly correlated with the amplitude of bending, but this relation was weaker
      for scoliotic subjects and this difference was worst at the apex vertebra. These
      results show that neuromuscular disorders could occur at a local level. The
      proposed approach should provide a simulation tool to study the multifactorial
      origin of scoliosis, and to investigate the implication of muscles and central
      commands in spinal dysfunctions.

PMID- 15456057
TI  - Rotation of the atlantico-axial joint, investigated using CT and MRI.
AB  - The vertebral column is composed of a series of joints, each capable of a
      specific range of movement. To investigate these movements, a study into the
      physiological range of rotation at the atlanto-axial joint has been undertaken.
      The movements and their interpretation under imaging conditions are crucial if
      any underlying spinal deformity or the consequences of trauma are present in an
      individual. 28 healthy volunteers were examined using dynamic Magnetic Resonance
      Imaging with maximum head rotation to the right and left sides in turn. An
      anatomical specimen of the atlanto-occipital joint was imaged using Computed
      Tomography with the specimen fixed in varying degrees of rotation. The results
      indicate that there is a significant but incomplete loss of contact between the
      articular surfaces of C1 (atlas) and C2 (axis). The range of motion to the right
      was between 20 and 48.5 degrees (mean 32.4 degrees) and to the left was between
      13 and 52.75 degrees (mean 3.2 degrees). Statistical significance between left
      and right movement was not demonstrated. The instantaneous axis of rotation was
      examined for the joint and was found to be located within the odontoid peg
      (dens). These findings indicated that a wide range of movement occurs within the
      atlanto-axial joint in normal subjects. Furthermore, the appearances under
      imaging could be misinterpreted as a pathological subluxation. This has
      implications if the subject with a spinal deformity also has a dysplasia
      associated with a potential subluxation. The siting of the instantaneous axis of
      rotation within the odontoid is also important in furthering the understanding of
      the movement of this joint.

PMID- 15456058
TI  - Comparison of mechanical behaviour of normal and scoliotic vertebral segment: a
      preliminary numerical approach.
AB  - Specific behaviour of the scoliotic spine has already been proven. The aim of
      this preliminary study is to evaluate if this behaviour is mainly due to
      geometrical deformities or to mechanical characteristics of soft tissues. We use
      a kriging technique to obtain a personalized finite element model of scoliotic
      spine from 3D reconstructions and from an existing detailed model of normal
      spine. To evaluate if deformed geometry has a share in specific behaviour of
      scoliotic spine, numerical simulations were performed on an apical segments
      extracted from normal and scoliotic models and the results were compared. Average
      mechanical properties of normal spine were considered in both models.

PMID- 15456059
TI  - Simulations of rib cage surgery for the management of scoliotic deformities.
AB  - Costoplasties are surgical options to treat rib cage deformities. The main
      concern of rib resections is often for the cosmetic improvement of the back shape
      of the patient. Other experimental and clinical studies have shown that a
      costoplasty can also produce mechanical correction of the spine. Based on the
      assumption that surgery on the rib cage can alter the equilibrium of forces
      acting on the spine, this study aims to investigate the biomechanical role of the
      ribs during the surgical treatment of scoliosis using a finite element model of
      the spine and rib cage. The model was generated from patient-specific geometric
      data. Concave side rib shortening and convex side rib lengthening have been
      simulated and evaluated. Slight post-operative immediate geometrical correction
      of the spine was found in any of the simulations. However, both kinds of
      simulation induced similar loads on the vertebral endplates. Resulting torques in
      the frontal plane tended to correct the scoliotic spine in the frontal plane
      acting against vertebral wedging. Important torques were also found in the
      sagittal plane, increasing the physiological kyphosis, and derotational torques
      promoted the improvement of the transverse plane deformation. This biomechanical
      analysis showed that appropriate rib surgery may counteract the progression of
      the spine deformity depending on the remaining growth potential. These findings
      support the concept of early interventions on the rib cage that may be a new
      approach of treatment to prevent curve progression in small to moderate
      idiopathic scoliotic deformities.

PMID- 15456060
TI  - Computer modelling of hooks for use as intra-operative force sensors.
AB  - There are a number of forces applied during scoliosis surgery, the magnitude and
      direction of which remains unknown. There is little literature concerning the in
      vivo distribution of forces along the spine. Computer modelling (ANSYS) was used
      to investigate the possibility of using an instrumented hook to intra-operatively
      measure the antero-posterior and distraction/compression forces applied by the
      surgeon during corrective scoliosis surgery. Three hook designs were evaluated
      based on specific design criteria. ANSYS provided the preliminary analysis to
      determine the strain distribution in these hooks. One design, the "membrane"
      design, was selected and a prototype was manufactured. Preliminary tests
      demonstrate that this prototype will be able to differentiate between the four
      major forces applied during the surgical correction.

PMID- 15456061
TI  - The role of disc, facets and fibres in degenerative process: a sensitivity study.
AB  - In order to have a better knowledge on the behaviour of the lumbar spine, we
      investigated the response under loads (flexion, extension, lateral bending and
      torsion) of a finite element model (L3-L5 segment) submitted to changes of
      parameters (disc height, nucleus Poisson coefficient, posterior disc fibres,
      facet orientation and asymmetry and gap). These changes were selected using a
      Taguchi planning method and the results obtained show that some parameters (disc
      height, gap, facet orientation) take a high part on motion and stresses while
      others have a slight influence. It also appears that some interactions between
      parameters play a significant role.

PMID- 15456062
TI  - Torsional deformity of apical vertebra in adolescent idiopathic scoliosis.
AB  - CT scans of structural thoracic idiopathic scoliosis were reviewed in nine
      patients admitted to our department for scoliosis surgery. The apical vertebra
      scans were chosen and the following parameters were evaluated: 1) alpha angle
      formed by the axis of vertebra and the axis of spinous process 2) beta concave
      and beta convex angle between the spinous process and the left and right
      transverse process, respectively, 3) gamma concave and gamma convex angle between
      the axis of vertebra and the left and right transverse process, respectively, 4)
      the rotation angle to the sagittal plane. The constant deviation of the spinous
      process towards the convex side of the curve was observed. The vertebral body
      itself was distorted towards the concavity of the curve. The angle between the
      spinous process and the transverse process was smaller on the convex side of the
      curve. The torsional, intravertebral deformity of the apical vertebra was a
      factor acting in the direction opposite to the rotation, in the sense to reduce
      the deformity of the spine in idiopathic scoliosis.

PMID- 15456063
TI  - A 3-D parametric biomechanical skeleton model for posture and spine shape
      analysis.
AB  - A project has been undertaken by our group to merge different segmental
      biomechanical models presented in literature into a full 3D parametric human
      skeleton representation, based on opto-electronic measurements. The obtained 3D
      skeleton model can then be fitted to each subject's anthropometrical
      characteristics. The accuracy and precision of this model relies both on
      anatomical findings (cadaver dissections, in vivo measurements, and parametric
      regression equations) reported in literature and on the approach and signal
      processing procedures we largely described and discussed in previous papers. The
      aim of this work is to present and describe the above mentioned 3D parametric
      biomechanical skeleton model. This model and the related graphical software
      package have been developed as a clinical tool for diagnostic and therapeutic
      purposes, and they are currently used in different clinical centres.

PMID- 15456064
TI  - Biomechanical modelling of spinal growth modulation for the study of adolescent
      scoliotic deformities: a feasibility study.
AB  - A model of growth modulation was formulated with variables integrating a
      biomechanical stimulus of growth modulation, a sensitivity factor to the stimulus
      and time. It was integrated into a finite element model of the thoracic and
      lumbar spine using an iterative procedure. A simulation on the personalized
      geometry of a mild scoliotic patient allowed qualitative investigation of
      scoliotic deformities over 12 cycles (months) in response to a load variation due
      to an eccentricity of the patient's gravity line in the frontal plane. Resulting
      frontal, sagittal and transverse spinal views correspond to clinically observable
      scoliotic configurations. The simulation adequately reproduces a progressing
      thoracic scoliotic curve while the slight increasing kyphosis represents a
      possible condition although a thoracic hypokyphosis is frequently reported in the
      literature. At the thoracic apex, increased wedging as well as axial rotation
      evolving towards curve convexity are in agreement with clinical and experimental
      observations reported with curve progression. This study demonstrates the
      feasibility of the approach and, compared to other biomechanical models, it
      achieves a more complete representation of the scoliotic spine by incorporating
      vertebral growth modulation.

PMID- 15456065
TI  - Growth plate chondrocyte enlargement modulated by mechanical loading.
AB  - Mechanical compression and distraction forces are known to modulate growth in
      vertebral growth plates, and are implicated in the progression of scoliosis. The
      amount of cellular enlargement is thought to be a key variable correlating with
      differing growth at different anatomical sites. This work tested the hypothesis
      that growth differences produced by mechanical loading are associated with
      alterations in the amount of cell height increase in the growth direction.
      Compression force (3 animals) or distraction force (4 animals) of 60% bodyweight
      was maintained on a caudal vertebra of growing rats with an external apparatus
      attached to vertebrae adjacent to the experimental level via transfixing pins.
      Growth of loaded and control vertebrae was measured from weekly radiographs.
      After four weeks, animals were euthanized and the loaded vertebrae and adjacent
      control vertebrae were excised for histological sections from which the following
      were measured: height of the hypertrophic zone (the average separation between
      boundaries of the zone); Mean Hypertrophic chondrocytic height; slope of the
      linear regression of cell height vs. position in the zone, (the amount of cell
      enlargement). Distracted and compressed vertebra growth averaged 110% and 53% of
      control levels. The percentage changes in the measures of chondrocyte dimensions,
      relative to control values, were smaller than the percentage changes in growth
      velocity. Also, the effects were of smaller magnitude for distracted vertebrae
      than for compressed vertebrae. Growth plate zonal height, slope and mean cell
      height all correlated significantly (p<0.05) with growth rate (expressed as a
      percentage of control) (Pearson r = 0.69, 0.37 and 0.41 respectively. Thus
      mechanical loading of tail vertebrae modulated their growth rate, that in turn
      correlated with changes in the amount of hypertrophic chondrocyte height
      increase. The effects for compression were greater than for distraction.

PMID- 15456066
TI  - Morphometric analysis of thoracic and lumbar vertebrae in idiopathic scoliosis.
AB  - The aim of this paper was to analyse the vertebral morphometry in idiopathic
      scoliosis with respect to pedicle screw instrumentation by means of computed
      tomography scans. The pedicle morphometry between T5 and L4 was analysed by
      computed tomography scans in 29 surgically treated patients with idiopathic right
      thoracic scoliosis. Measurements included chord length, endosteal transverse
      pedicle diameter and transverse pedicle angle. The endosteal transverse pedicle
      diameter was significantly smaller (P<0.05) on the concavity in the apical region
      of the thoracic spine. The chord length was the shortest at the fifth thoracic
      vertebra with significantly larger dimensions on the concavity of the apical
      region in the thoracic spine (P<0.05). The transverse pedicle angle varied
      between 6 degrees in the lower thoracic spine and 12 degrees at the upper
      thoracic and lower lumbar spine. The morphometry in scoliotic vertebrae is
      substantially different from those in normal spines with an asymmetrical intra
      vertebral deformity. Pedicle screw instrumentation in the middle thoracic spine
      appears critical due to the small endosteal pedicle diameter, especially on the
      concave side.

PMID- 15456067
TI  - Morphometric analysis of one anatomic scoliotic specimen.
AB  - Idiopathic scoliosis is a 3-D deformation affecting the position of the spine in
      space. The regional deformity has been studied extensively but the local changes
      have not been widely investigated and this being mainly due to the rarity of
      anatomical specimens. The objective of this study was to identify a deformation
      pattern for idiopathic scoliosis. We thus studied one complete scoliotic specimen
      using a digitizing protocol developed by our research group. The anatomical
      specimen was selected from the Hamann-Todd Osteology Collection at the Cleveland
      Natural History Museum, which contains over 1,300 skeletons. We were also able to
      match this scoliotic specimen with one normal specimen for age, sex, race, height
      and weight. Each vertebra was measured by taking approximately 200 points on each
      surface. Parameters for each vertebra were then calculated from these sets of
      points. Each scoliotic vertebra was then compared with a corresponding normal
      vertebra of the matched specimen. We present the first findings of these
      measurements, which show pedicle and posterior elements changes that are thought
      to be secondary to the scoliotic deformation.

PMID- 15456068
TI  - Coronal and transverse plane trunk asymmetry correction following torsional
      segmental spinal instrumentation for idiopathic scoliosis.

PMID- 15456069
TI  - Status of the spinal canal and spinal cord before and after surgical correction
      of severe scoliotic deformities of the spine on Cotrel-Dubousset methods.

PMID- 15456070
TI  - Relation between patient positioning, trunk flexibility and surgical correction
      of the scoliotic spine.
AB  - The purpose of this work is to investigate the relations between the correction
      of idiopathic scoliosis obtained by surgical instrumentation and the positioning
      of the patient on the surgical table as well as the curve reduction following the
      bending test. A retrospective study of preoperative standing, supine and lateral
      bending films as well as postoperative standing films was made using multiple
      regressions in order to identify the most significant parameters and define
      linear statistical models to predict the surgical correction. Postoperative
      thoracic Cobb angle is significantly associated to left and right bending Cobb
      angles and the post-op lumbar Cobb is associated to the supine and the left
      bending Cobb angles. This preliminary study suggests that such parameters should
      be considered in the pre-operative planning of surgery as well as in
      biomechanical models to obtain more adequate predictive values of the surgical
      outcome and to better understand the biomechanics of scoliosis surgical
      correction.

PMID- 15456071
TI  - Outcome of Harrington surgery for idiopathic scoliosis. SF-36 and Roland
      questionnaires assessment.

PMID- 15456072
TI  - In vivo quantitative analysis of scoliotic vertebrae.
AB  - An in vivo method based on CT images and finite element meshing had been
      developed to quantify and visualize the bone density distribution of scoliotic
      vertebrae. CT examination (axial acquisition of the apical, superior and inferior
      adjacent vertebral bodies) had been performed on seven girls presenting an
      idiopathic scoliosis. Using an in-house image processing software and the pre
      post processor Patran, a surfacic finite element mesh of each body slice was
      proposed allowing an automatic mapping of the cancellous bone slices and a
      volumic mesh for the bone density distribution visualization. In the coronal
      plane, compared to the body geometrical centre, the body mechanical centre was
      shifted forward in the concavity of the curvature for six patients and in the
      convexity for one patient. For each patient, this shift forward was made in a
      same way for the three vertebrae. In the sagittal plane, the body mechanical
      inertia centre was shifted forward in the posterior side for 12 vertebrae, in the
      anterior side for 3 vertebrae and was not shifted forward for 6 vertebrae. This
      shift forward was made in the anterior side for the inferior adjacent vertebra.
      The shift forward by slice was made in a same way for each slice, excepted at the
      end plates. Besides, one can observe that the scoliotic deformation evolution
      seemed to modify the mechanical property distribution. The results may also
      suggest predictive criteria of evolution of the scoliotic deformities.

PMID- 15456073
TI  - Intraoperative tracking of the trunk during posterior instrumentation of the
      scoliotic spine: a feasibility study.
AB  - Scoliosis involves spine and trunk deformities. However, during posterior
      instrumentation of the scoliotic spine, only the exposed spine is currently seen
      or tracked using navigation systems. A technique for intraoperative tracking of
      the trunk was developed in order to optimize the surgical correction of the
      scoliotic trunk deformity. The feasibility of this technique was assessed by
      comparing the trunk geometry between 19 normal and 21 scoliotic subjects, using
      an experimental set-up simulating the position adopted during posterior scoliosis
      surgery. Eleven magnetic sensors placed on anatomical landmarks of the trunk were
      used to compute nine geometric indices. The geometric indices were closer to zero
      for normal subjects. Therefore, indices approaching zero during the surgical
      manoeuvres would indicate a reduction of the trunk asymmetry. Only three of the
      nine indices were significantly different between normal and scoliotic subjects.
      This result indicates that the positioning of the subjects on the Relton-Hall
      frame tends to "normalize" the trunk geometry since the standing position gives
      more significant differences between normal and scoliotic subjects. The real-time
      quantification of the trunk geometry during surgical correction of scoliosis may
      allow the surgeon to improve the correction of both spinal and trunk deformities
      or to optimize the positioning of the patients on the operating table.

PMID- 15456074
TI  - Biomechanical simulation of Colorado instrumentation of the scoliotic spine: a
      preliminary study.
AB  - Few biomechanical models of the scoliotic spine were developed to simulate the
      Cotrel-Dubousset instrumentation, although none was dedicated to the Colorado
      system. The objective of this study is to adapt and assess an existing
      biomechanical model to simulate the effect of the Colorado instrumentation of the
      scoliotic spine as a function of pre-operative geometry and surgical planning.
      Fifteen scoliotic patients operated with a Colorado system were analysed using a
      knowledge extraction technique to simplify surgical procedure and to establish
      the biomechanical model (boundary conditions, simulation procedures,...).
      Preliminary results on one patient show that the Colorado surgical technique can
      be adequately modelled using the preoperative geometric data and limited
      simulation strategy parameters.

PMID- 15456075
TI  - Feasibility study of patient-specific surgical templates for the fixation of
      pedicle screws.
AB  - Surgery for scoliosis, as well as other posterior spinal surgeries, frequently
      uses pedicle screws to fix an instrumentation on the spine. Misplacement of a
      screw can lead to intra- and post-operative complications. The objective of this
      study is to design patient-specific surgical templates to guide the drilling
      operation. From the CT-scan of a vertebra, the optimal drilling direction and
      limit angles are computed from an inverse projection of the pedicle limits. The
      first template design uses a surface-to-surface registration method and was
      constructed in a CAD system by subtracting the vertebra from a rectangular prism
      and a cylinder with the optimal orientation. This template and the vertebra were
      built using rapid prototyping. The second design uses a point-to-surface
      registration method and has 6 adjustable screws to adjust the orientation and
      length of the drilling support device. A mechanism was designed to hold it in
      place on the spinal process. A virtual prototype was build with CATIA software.
      During the operation, the surgeon places either template on patient's vertebra
      until a perfect match is obtained before drilling. The second design seems better
      than the first one because it can be reused on different vertebra and is less
      sensible to registration errors. The next step is to build the second design and
      make experimental and simulations tests to evaluate the benefits of this template
      during a scoliosis operation.

PMID- 15456076
TI  - HIV susceptibility testing--time for standards.

PMID- 15456077
TI  - Clinically validated genotype analysis: guiding principles and statistical
      concerns.
AB  - Whereas previously the output of HIV resistance tests has been based on
      therapeutically arbitrary criteria, there is now an ongoing move towards
      correlating test interpretation with virological outcomes on treatment. This
      approach is undeniably superior, in principle, for tests intended to guide drug
      choices. However the predictive accuracy of a given stratagem that links genotype
      or phenotype to drug response is strongly influenced by the study design, data
      capture and analytical methodology used to derive it. For genotyping, the most
      widely used resistance tool in clinical practice, these considerations are
      further complicated by the range of mutational patterns present in the treated
      population. There is no definitively superior methodology for generating a
      genotype-response association for use in interpreting a resistance test, and the
      various approaches used to date all have their strengths and weaknesses. This
      review discusses the processes involved in constructing such tools, with
      particular emphasis on establishing validated mutation score rules, and examines
      the key issues and confounding factors that influence predictive accuracy outside
      the originating dataset. Since the size of the sample is a key influence on the
      statistical power to determine an effect, it is hoped that a greater
      understanding of the influence of study design and methodology will assist the
      development of standardized outcome measures and reporting formats that allow
      data pooling at the international level.

PMID- 15456078
TI  - Activation of dendritic cells and induction of T cell responses by HPV 16 L1/E7
      chimeric virus-like particles are enhanced by CpG ODN or sorbitol.
AB  - Chimeric human papillomavirus-like particles, consisting of human papillomavirus
      (HPV) 16 L1-E7 fusion proteins [HPV 16 L1/E7 chimeric virus-like particles
      (CVLP)], are a vaccine candidate for treatment and prevention of cervical cancer.
      Although in preclinical studies CVLPs were shown to induce neutralizing
      antibodies and L1- and E7-specific T cell responses, the results of a recent
      clinical trial emphasized the need of improved immunogenicity of CVLPs. Here we
      studied the interaction of HPV 16 L1/E7 CVLPs with mouse bone marrow-derived
      dendritic cells (BMDCs) activated with different immune adjuvants. We found that
      lipopolysaccharides (LPS), unmethylated CpG motifs (CpG ODN) and sorbitol
      enhanced CVLP-induced stimulation of C57BL/6 mouse BMDCs as revealed by increased
      levels of CD40, CD80, MHC II and CD54 at the cell surface. CpG ODN and sorbitol
      also enhanced the presentation of Db-restricted cytotoxic T lymphocyte epitopes
      to HPV 16 L1- or E7-specific T lymphocytes after loading of CVLPs onto BMDCs.
      Treatment of BMDCs with CpG ODN in combination with CVLPs improved in vitro
      priming of naive T lymphocytes by CVLP-loaded BMDCs. In vivo, CVLP-loaded BMDCs
      were more immunogenic as compared with injection of CVLPs alone. CpG ODN and
      sorbitol further enhanced priming of antigen-specific T cell responses. Our data
      demonstrate that CpG ODN- or sorbitol-activated BMDCs substantially increase the
      immunogenicity of CVLPs. Implementing our results in clinical trial protocols may
      lead to improved activity of therapeutic HPV vaccines for the treatment of HPV
      induced cancer.

PMID- 15456079
TI  - Viral dynamics and pharmacokinetics of peginterferon alpha-2a and peginterferon
      alpha-2b in naive patients with chronic hepatitis c: a randomized, controlled
      study.
AB  - The two available pegylated interferon formulations, peginterferon alpha-2a and
      peginterferon alpha-2b, have different pharmacokinetic profiles; as a result they
      may have differing abilities to suppress the hepatitis C virus. A recently
      reported study by Formann and colleagues assessing early viral kinetics among 20
      patients receiving peginterferon alpha-2b either once or twice weekly suggests
      that once-weekly administration of peginterferon alpha-2b is not sufficient for
      continuous exposure to interferon over 160 h. Twice-weekly administration is
      recommended to avoid increases in viral load as interferon levels decline prior
      to the end of the one-week dosing period. The objective of this study was to
      compare viral dynamics and pharmacokinetics between peginterferon alpha-2a and
      peginterferon alpha-2b in interferon-naive chronic hepatitis C patients. Patients
      were randomized to receive peginterferon alpha-2a 180 microg (n=10) or
      peginterferon alpha-2b 1.0 microg/kg (n=12) once weekly. Serum peginterferon
      concentrations were measured at baseline, 24, 48, 120 and 168h. Hepatitis C virus
      (HCV) RNA was measured at baseline, 24, 48, 120 and 168 h during week 1 and then
      at 4 and 12 weeks. Peginterferon alpha-2b achieved maximal serum levels at 24 h,
      and then decreased rapidly. Of the 12 patients who received peginterferon alpha
      2b, no drug was detectable in seven (58%) patients at 120 h and in 11 (92%) at
      168 h. In contrast, peginterferon alpha-2a concentrations increased continuously
      over time, reaching maximal serum levels from 48 to 168 h. Drug was detectable in
      all 10 patients at 168 h. At weeks 1 and 4 no significant difference was observed
      in mean HCV RNA between the groups. However, at week 12, mean HCV RNA was
      significantly lower in the peginterferon alpha-2a group versus the peginterferon
      alpha-2b group (2.8126 vs 3.8726; P<0.01). The differences in mean HCV RNA values
      at 12 weeks may be related to the different absorption and distribution profiles
      of the two drugs. In conclusion, once-weekly administration of peginterferon
      alpha-2b (1.0 microg/kg/wk) may be insufficient for continuous interferon
      exposure; twice-weekly administration may help avoid increases in viral
      replication as interferon levels decline. Larger-scale studies assessing both
      viral kinetics and sustained virological responses are needed to confirm these
      observations.

PMID- 15456080
TI  - Peginterferon alpha-2b plus ribavirin with or without amantadine [correction of
      amantidine] for the treatment of non-responders to standard interferon and
      ribavirin.
AB  - BACKGROUND: A significant proportion of hepatitis C patients treated with
      unmodified interferon plus ribavirin fail to respond. The optimal therapy for
      these patients has not been established yet. The objective of this study was to
      assess the efficacy and safety of peginterferon plus ribavirin with or without
      amantidine in such patients. METHODS: In this open-label, prospective controlled
      trial, a total of 63 patients were randomly divided into groups A and B with a
      ratio of 1:2. Group A (21 patients) received weekly peginterferon alpha-2b, 1.5
      microg/kg concomitantly with ribavirin 1000-1200mg per day. Group B (42 patients)
      received peginterferon and ribavirin as in group A, plus amantadine [corrected]
      200 mg per day. RESULTS: At the completion of treatment, serum levels of
      hepatitis C virus RNA were undetectable in 14% and 12% of patients in groups A
      and B, respectively (P=NS). Hepatitis C virus RNA remained undetectable 24 weeks
      after the end of treatment in one patient (5%) in group A and three patients (7%)
      in group B (P=NS). Sustained viral clearance was associated with sustained
      normalization of serum alanine aminotransferase level. Both drug regimens had
      similar side effect profiles. CONCLUSION: Peginterferon plus ribavirin therapy
      with or without amantadine [corrected] is associated with a low sustained
      virological response in patients who failed interferon and ribavirin combination
      therapy.

PMID- 15456081
TI  - Hepatitis C virus-RNA clearance in HIV-coinfected patients with chronic hepatitis
      C treated with pegylated interferon plus ribavirin.
AB  - Hepatitis C virus (HCV)-RNA clearance seems to occur more slowly in HIV/HCV
      coinfected patients than in HCV-monoinfected subjects treated with pegylated
      interferon alpha (peg-IFN) plus ribavirin (RBV). As a consequence, concern has
      arisen over the feasibility of following the treatment rules applied to HIV
      negative patients with chronic hepatitis C. A total of 89 HIV/HCV-coinfected
      patients who had fully completed a course of peg-IFN plus RBV were analysed. Of
      these, 29 (32.6%) reached sustained virological response (SVR). Reductions >2
      logs in plasma HCV-RNA occurred in 52 (58%) patients at week 12 of treatment
      (early virological response; EVR). None of patients who showed HCV-RNA drops <2
      logs at week 12 reached SVR (negative predictive value: 100%). The positive
      predictive value of EVR was 56%. On the other hand, relapses occurred in 19
      (39.6%) out of the 48 patients who had negative HCV-RNA at the end of treatment,
      and there were no differences noted when comparing patients with HCV genotypes
      2/3 and 1/4. In summary, the quantitative assessment of plasma HCV-RNA at week 12
      predicts the chance of SVR using peg-IFN plus RBV in HIV-positive patients with
      chronic hepatitis C, as it does in HIV-negative individuals. Thus,
      discontinuation of anti-HCV therapy, which is associated with frequent side
      effects, might be warranted in HIV/HCV-coinfected patients showing HCV-RNA
      reductions <2 logs at week 12 of treatment. On the other hand, relapses in
      virological responders were unexpectedly high in HIV/HCV-coinfected patients when
      treatment was provided following the rules applied to HIV-negative subjects. This
      is particularly relevant for HCV genotypes 2/3, which only rarely relapse in HIV
      negative patients. Therefore, extending therapy (for 12 months in HCV genotypes
      2/3 and perhaps for 18 months in HCV genotypes 1/4) might be warranted in HIV/HCV
      coinfected patients showing EVR.

PMID- 15456082
TI  - Gynaecomastia in HIV-infected men on highly active antiretroviral therapy:
      association with efavirenz and didanosine treatment.
AB  - BACKGROUND: Gynaecomastia has been described in HIV-infected men undergoing
      highly active antiretroviral therapy (HAART). However, there are insufficient
      data on the relationship between gynaecomastia and any specific antiretroviral
      drug and hormone abnormality. OBJECTIVE: To assess the frequency of gynaecomastia
      in HIV-infected men receiving HAART and its association with antiretroviral drugs
      and hormone abnormalities. METHODS: We carried out a prospective study of 1304
      HIV-infected men undergoing HAART. In addition, we included a case (with
      gynaecomastia)-control (without gynaecomastia) analysis in the second part of
      this study. Cases and controls were matched according to age, HIV infection CDC
      clinical category, HCV infection, the date of study and the physician responsible
      for the patient. Patients bearing known causes of gynaecomastia were excluded. We
      analysed epidemiological, clinical, haematological and immunological
      characteristics and the use and duration of the antiretroviral therapy. In 13
      cases and 13 controls a sexual hormone profile was carried out. RESULTS: A total
      of 30 (2.3%) HIV-infected men presented with gynaecomastia of unexplained cause.
      In 22 (73%) of these individuals, gynaecomastia completely resolved after a
      median time of 9 months (range: 5-22 months). The percentage of individuals who
      were receiving efavirenz and didanosine at the time of the study was higher among
      patients with gynaecomastia [57% vs 17% (P=0.004) and 50% vs 13% (P=0.003),
      respectively]. Plasma total testosterone, free testosterone index and
      bioavailable testosterone levels were lower in patients with gynaecomastia,
      whereas plasma free testosterone levels were not significantly different in
      either population. CONCLUSIONS: Gynaecomastia is not uncommon in HIV-infected men
      undergoing HAART and it is usually transient. Efavirenz and didanosine treatment
      are associated with the emergence of gynaecomastia. An underlying hypoandrogenism
      seems to contribute to the emergence of this disorder in these patients.

PMID- 15456083
TI  - ATP binding cassette multidrug transporters limit the anti-HIV activity of
      zidovudine and indinavir in infected human macrophages.
AB  - OBJECTIVES: To investigate whether P-glycoprotein (P-gp) and multidrug resistance
      proteins (MRPs), which limit the bioavailability of HIV protease inhibitors (PIs)
      and nucleoside reverse transcriptase inhibitors (NRTIs), modulate the anti-HIV
      activity of NRTIs, non-NRTIs and PIs in vitro. DESIGN: We used primary cultures
      of major HIV target cells: human monocyte-derived macrophages (MDMs) and
      lymphocytes. METHODS: P-gp and MRP expression in response to long-term zidovudine
      (3'-azido-3'-deoxythymidine; AZT) or indinavir treatment was quantified by RT
      PCR. MDM and lymphocytes were infected in vitro with HIV-1/Ba-L and HIV-1-LAI,
      respectively, and treated with antiretroviral drugs. We evaluated the activity of
      these drugs in combination with PSC833, a P-gp inhibitor, and/or probenecid, an
      MRP1 inhibitor. Intracellular AZT triphosphate derivative (AZT-TP) was quantified
      by HPLC-MSMS. P-gp ATPase activity was measured with inside-out native membrane
      vesicles enriched in P-gp. RESULTS: Levels of MDR1, mrp4 and mrp5 mRNA were high
      following AZT treatment. In infected MDM, PSC833 and probenecid increased the
      anti-HIV activity of AZT and indinavir. AZT (5 nM) decreased HIV replication by
      34% alone and by 72% in combination with P-gp/MRP inhibitors. Indinavir (10 nM)
      gave 14% inhibition alone and 81% in combination. The increase in anti-HIV
      activity of AZT was correlated with an increase in intracellular AZT-TP
      concentration. However, unlike PIs, neither AZT nor its metabolites interacted
      with P-gp. CONCLUSION: AZT increases the expression of multidrug transporters,
      thereby decreasing its pharmacological activity. The cellular efflux of AZT
      probably involves MRP4 or MRP5. In contrast, increases in indinavir anti-HIV
      activity require the inhibition of both P-gp and MRP1.

PMID- 15456084
TI  - Potent antiviral effect of reverset in HIV-1-infected adults following a single
      oral dose.
AB  - Reverset (2',3'-didehydro-2',3'-dideoxy-5-fluorocytidine, RVT) is a potent
      inhibitor of HIV-1 replication in cell culture, with a 90% effective
      concentration at or below 1 microM. In vitro, RVT retains its activity against
      isolates harbouring mutations in the reverse transcriptase (RT) gene that
      otherwise confer resistance to lamivudine and/or zidovudine. The pharmacokinetics
      and safety of single oral doses of RVT (10-200 mg) were evaluated in an initial
      Phase I clinical trial. The viral load changes were determined on 18 HIV-1
      infected antiretroviral therapy-naive subjects that were randomized into three
      cohorts, each cohort consisting of three study periods. The subjects received up
      to two oral doses of active drug and one placebo dose with a 1-week washout
      period separating the three study periods. Quantification of viral RNA was
      performed on the pre-dose, 12, 24 and 48 h post-dose plasma samples. A single
      oral dose of RVT to antiretroviral-naive subjects significantly reduced plasma
      viral load by 0.45 +/- 0.10 log10 copies/ml (P=0.0003). A mean drop of 0.37 +/-
      0.12 log10 copies/ml (P=0.001) was obtained at the lowest dose of 10 mg. Sequence
      analysis of the HIV-1 RT gene performed before and after RVT dosing detected no
      genotypic changes in this short-term study. The viral RT gene of one subject had
      at predose the following genotype: L41 + N103 + C181 + W210 + D215, indicating
      prior exposure to zidovudine and non-nucleoside analogues, and anticipating high
      level resistance against these agents. A single 10 mg RVT dose resulted in a
      viral load drop of 0.61 +/- 0.05 log10 providing evidence that a viral strain
      with the indicated genotype is susceptible to RVT.

PMID- 15456085
TI  - The NIQ of lopinavir is predictive of a 48-week virological response in highly
      treatment-experienced HIV-1-infected subjects treated with a lopinavir/ritonavir
      containing regimen.
AB  - OBJECTIVE: To investigate the normalized inhibitory quotient (NIQ) of lopinavir
      (LPV) as a predictor of 48-week virological responses to a lopinavir/ritonavir
      (LPV/RTV)-containing regimen in highly treatment-experienced patients. DESIGN: We
      calculated the NIQ for 59 patients who completed 48 weeks' treatment and assessed
      the factors predicting a week-48 virological response. METHODS: The NIQ was
      calculated by dividing each subject's IQ (LPV Ctrough/fold change in LPV
      susceptibility, as assessed by VirtualPhenotype) by a reference IQ (mean
      population LPV Ctrough/fold change in LPV IC50, as assessed by VirtualPhenotype).
      HIV-1 RNA was assessed by NASBA (quantification limit: 80 copies/ml). The general
      linear model and multiple logistic regression, respectively, were used to
      estimate the independent predictors of a change in viral load and HIV-1 RNA <80
      copies/ml. RESULTS: The median (interquartile range) baseline levels of CD4+
      cells and HIV-1 RNA were 251 (141-385) cells/microl and 4.85 (4.49-5.23) log10
      copies/ml, respectively. The median NIQ was 2.2 (0.5-14). At week 48, the median
      decrease in HIV-1 RNA was 1.4 (0.59-2.79) log10 copies/ml (P<0.0001), with 24
      subjects (41%) reaching <80 copies/mi. Baseline HIV-1 RNA (P=0.001), CD4+ cells
      (P=0.002) and NIQ (P=0.0006) independently predicted the week-48 change in viral
      load, whereas baseline CD4+ cells (P=0.011) and NIQ (P=0.009) independently
      predicted a week-48 HIV-1 RNA level of <80 copies/ml. CONCLUSION: The LPV NIQ
      independently predicts virological responses to an LPV/RTV-containing regimen in
      highly treatment-experienced HIV-1-infected patients.

PMID- 15456086
TI  - Prostratin induces HIV activation and downregulates HIV receptors in peripheral
      blood lymphocytes.
AB  - Induction of HIV expression through lymphocyte activation has been proposed as a
      strategy to purge latent reservoirs. Prostratin is a non-tumourogenic phorbol
      ester that delays HIV replication in vitro, but paradoxically activates HIV
      expression in latently infected cells. To get a better insight into the
      mechanisms of action of prostratin, we have analysed the effect of prostratin on
      HIV activation and HIV receptor and coreceptors' surface expression in human
      lymphocytes. Peripheral blood mononuclear cells (PBMCs) were transfected with
      luciferase expression constructs under the control of wild type HIV-long terminal
      repeat (LTR) and consensus sequences for transcription factors involved in HIV
      LTR transactivation (NF-kappaB, SP1, NFAT). Prostratin stimulates transactivation
      of LTR vectors, kappaB- and SP-1-driven luciferase constructs. In another set of
      experiments, PBMCs were transfected with a full-length infectious viral clone.
      Prostratin induced HIV transcription and viral expression as detected by
      luciferase activity in cellular extracts and p24 levels in culture supernatants,
      respectively. Expression of the HIV coreceptors CCR5 and CXCR4 was decreased by
      prostratin and, concomitantly, prostratin inhibited the infection of PBMCs with
      R5 and X4 strains. However, prostratin did not inhibit infection with a
      pseudotyped viral clone that enters into the cells independently of HIV
      receptors. These results help to explain the paradoxical effects of prostratin.
      On one hand, prostratin induces HIV activation in latently infected cells through
      the induction of NF-kappaB and Sp1. On the other hand, strong and persistent
      downregulation of HIV receptors decreases infection of new targets and delays HIV
      propagation. These data support the potential use of prostratin to activate HIV
      from latency and purge viral reservoirs.

PMID- 15456087
TI  - Altered fat differentiation and adipocytokine expression are inter-related and
      linked to morphological changes and insulin resistance in HIV-1-infected
      lipodystrophic patients.
AB  - OBJECTIVE: To achieve a better understand of the pathophysiology of HIV-related
      lipoatrophy, we compared the mRNA expression of adipocytokines in fat samples
      from patients and healthy HIV-seronegative controls together with fat morphology
      and we studied the relationship between changes in fat morphology, adipocytokine
      expression, markers of adipose tissue differentiation and whole body insulin
      sensitivity. DESIGN: Cross-sectional analytical study. SUBJECTS AND METHODS: The
      mRNA expression of adipocytokines and transcriptional factors in fat samples from
      26 patients with peripheral lipoatrophy (all under anti-retroviral therapy
      associating protease inhibitor and nucleoside-analogue reverse transcriptase
      inhibitors) and from 16 non-HIV-infected controls was measured by real time
      quantitative RT-PCR. Fat morphology was assessed histologically on a subgroup of
      10 patients and six controls: collagen fibres by Sirius Red staining, apoptosis
      by the TUNEL technique, vessels by smooth muscle alpha-actin staining and
      macrophages by CD68 staining. Insulin resistance was assessed by using the
      homeostasis model assessment. RESULTS: The patients' fat showed higher values of
      apoptosis (P=0.005), fibrosis (P<0.05), vessel density (P=0.001) and macrophage
      infiltration (P<0.05) than the controls' fat, together with lower adiponectin and
      leptin mRNA levels and higher interleukin (IL)-6 and tumour necrosis factor
      (TNF)alpha mRNA levels. TNFa and IL-6 expression correlated positively with the
      level of apoptosis (P=0.05 and P<0.05, respectively) and negatively with CCAAT
      enhancer binding protein (C/EBP)alpha (P<0.001 and P<0.05, respectively).
      Apoptosis correlated negatively with the expression level of sterol-regulatory
      element-binding-protein-1c (SREBP1c) (P=0.01) and C/EBPalpha (P=0.01) whilst the
      vessel density correlated negatively with SREBP1c (P<0.005), C/EBPalpha (P=0.001)
      and beta (P=0.001). Adiponectin and leptin expression correlated positively with
      each other, and also with adipogenic marker expression and overall insulin
      sensitivity. These relationships were also present when the patient group was
      studied separately. Finally, fat morphological abnormalities correlated
      positively with whole body insulin resistance. CONCLUSIONS: Adipose tissue from
      patients with HIV-1-related lipoatrophy shows increased apoptosis, together with
      decreased adipocyte differentiation. Increased TNFalpha and IL-6 expression could
      be a major phenomenon linking these alterations. Decreased adiponectin and leptin
      expression, which may result from decreased adipocyte differentiation, could be
      involved in the observed whole body insulin resistance.

PMID- 15456088
TI  - Genotypic and phenotypic characterization of acyclovir-resistant herpes simplex
      viruses isolated from haematopoietic stem cell transplant recipients.
AB  - Thirty-one herpes simplex virus type one (HSV-1) isolates from 12 haematopoietic
      stem cell transplant recipients with persistent HSV infections despite acyclovir
      (ACV) prophylaxis or treatment, were genotypically and phenotypically
      characterized. The relationship between drug susceptibility of the isolates and
      mutations in thymidine kinase (TK) and DNA polymerase (DNA pol) genes was
      examined. In all 12 patients, HSV infections were due to ACV-resistant, foscarnet
      sensitive viruses. Out of 31 isolates examined, 23 were resistant and eight were
      sensitive to ACV; eight patients carried viruses with frameshift mutations in the
      TK gene (due to addition or deletion of single nucleotides in homopolymeric
      repeats). These mutations were found at codon 61 (G deletion, one patient), 146
      (G insertion, five patients) and 153 or 185 (C deletion, one patient each). In
      four patients, viruses were selected during ACV therapy that contained novel
      amino acid substitutions in the TK gene (H58R, G129D, A189V, R216H, R220C). Their
      possible role in ACV resistance was further confirmed phenotypically and by the
      absence of any resistance-associated mutations in the DNA pol gene. These
      substitutions were located in ATP- or nucleoside-binding sites or in conserved
      regions of the TK gene. In addition, a single mutation, Q570R, in the delta
      region C of the DNA pol gene, was identified in an isolate from a single patient
      with resistance to ACV. Our study confirms and expands previous data on genotypic
      changes associated with ACV resistance of HSV-1 clinical isolates.

PMID- 15456089
TI  - A reverse genetics study of resistance to neuraminidase inhibitors in an
      influenza A/H1N1 virus.
AB  - A system of reverse genetics was used to generate influenza A/H1N1 viruses
      harbouring neuraminidase (NA) mutations previously associated with resistance to
      NA inhibitors in various viral subtypes. The His274Tyr and Glu119Gln mutants were
      rescued whereas the Arg292Lys and Glu1l9 --> Gly, Val, Ala or Asp mutants could
      not be generated. In NA inhibition assays, the His274Tyr mutant was resistant to
      oseltamivir (430-fold over wild-type) and BCX-1812 (50-fold) but was sensitive to
      zanamivir. A similar trend was seen when the mutant was evaluated by plaque
      reduction assay (PRA). The Glu119Gln mutant expressed a low level of resistance
      to oseltamivir (nine-fold) and zanamivir (fourfold) in NA inhibition assay but
      was only marginally resistant to oseltamivir (fourfold) in PRA. The replication
      capacity of both mutants, in particular that of the His274Tyr virus, was impaired
      when compared with the wild-type virus in vitro.

PMID- 15456090
TI  - Construction, training and clinical validation of an interpretation system for
      genotypic HIV-1 drug resistance based on fuzzy rules revised by virological
      outcomes.
AB  - OBJECTIVES: To evaluate whether fuzzy operators can be usefully applied to the
      interpretation of genotypic HIV-1 drug resistance by experts, and to improve the
      prediction of salvage therapy outcome by adapting interpretation rules of
      genotypic resistance on the basis of their association with virological response
      data. METHODS: We used a clinical dataset of 231 patients failing highly active
      antiretroviral therapy (HAART) and starting salvage therapy with baseline
      resistance genotyping and virological outcomes after 3 and 6 months. A set of
      rules predicting genotypic resistance was initially derived from an expert (ADL).
      Rules were implemented using a fuzzy logic approach and the virological outcomes
      dataset used for the training phase. The resulting algorithm was validated using
      a separate set of 184 selected patients by correlating the resulting predicted
      activity with observed virological response at 3 months. For comparison, the
      expert systems from the drug resistance group of the Agence Nationale de
      Recherches sur le SIDA (ANRS-AC11) and the algorithm from the Stanford's HIV drug
      resistance database (Stanford HIVdb) were evaluated on the same set. RESULTS: The
      starting algorithm had a correlation with virological outcomes of R2=0.06
      (P=0.0001). After the training phase the correlation with virological outcomes
      increased to R2=0.19 (P<0.000001). In the validation set of patients, the
      activity of the salvage regimen predicted by the fuzzy algorithm was the only
      variable independently predictive of the 3-month viral load change even after
      adjusting by the activity predicted by the two expert systems and baseline viral
      load (for each 10% salvage regimen's activity increase, mean HIV RNA change from
      baseline: -0.27 log10 copies/ml; 95% CI -0.39, -0.15). CONCLUSION: Using fuzzy
      operators in a virological outcomes training database to implement a rules-based
      algorithm for genotypic resistance interpretation, significant improvements of
      outcomes prediction were obtained. The resulting algorithm showed an independent
      predictive capability of virological outcomes over that of two rules-based
      interpretation algorithms made by experts. Although the system was trained and
      validated on a limited number of cases, the approach deserves further evaluation.

PMID- 15456091
TI  - Predictive value of HIV-1 protease genotype and virtual phenotype on the
      virological response to lopinavir/ritonavir-containing salvage regimens.
AB  - The predictive values of HIV-1 protease genotype and virtual phenotype
      (vPhenotype) results on the HIV-1 RNA response to lopinavir/ritonavir (LPV/r)
      containing salvage regimens were assessed. Data were evaluated from patients with
      antiretroviral (ARV) resistance testing prior to initiating an LPV/r-containing
      salvage ARV regimen, from two independent cohorts from Toronto, Ontario and
      British Columbia, Canada. Multivariate logistic regression models controlling for
      previous non-nucleoside reverse transcriptase inhibitor use, baseline viral load
      and AIDS-defining illness were used to assess the impact of different protease
      genotypic mutations (individual and in combination) and lopinavir vPhenotyping on
      virological suppression to <50 copies/ml by 12 months. We confirmed that the 11
      mutation 'lopinavir mutation score' (LMS) was significantly inversely associated
      with the probability of virological suppression within 12 months [odds ratio
      (OR)=0.91; P=0.02]. The only single specific protease mutation found to predict
      virological response in multivariate analyses was 461 (OR=0.55; P=0.02). The most
      predictive three-mutation combination was 10F/I/R/V, 461, 82A/F/T (OR=0.18;
      P=0.0004). We confirmed that a 10-fold increase of lopinavir IC50 is an
      appropriate clinical cut-off for lopinavir vPhenotype. In univariate analyses, a
      cut-off of the LMS as low as 3 was significantly associated with a lack of
      virological suppression (P=0.04). This finding, which is in contrast to those of
      other studies, may be due to the high degree of ARV experience of our population
      and lack of active agents in the salvage regimen. Selecting the 11 specific
      mutations to make the LMS is potentially arbitrary; we determined that when
      different combinations of 11 protease mutations were chosen randomly from a set
      of 30, similar associations with virological response were found, probably due to
      the co-linearity of these mutations.

PMID- 15456092
TI  - Immunomodulation induced by tucaresol in HIV infection: results of a 16 week
      pilot Phase I/II trial.
AB  - OBJECTIVE: Immune reconstitution in highly active antiretroviral therapy (HAART)
      treated individuals is incomplete and immunomodulatory compounds are needed to
      improve the outcome of HIV therapy. In a Phase I/II clinical trial performed on
      HIV-positive patients we analysed the safety and immunomodulating effects of
      tucaresol, a novel compound that has previously been described tn enhance cell
      mediated immune responses. PATIENTS AND METHODS: Sixteen weeks pulse dose
      escalation protocol. Four groups of HIV-positive patients were enrolled: group A
      (n=6): HAART, CD4+ 300-500 cells/microl, HIV RNA <80 copies/ml; group B (n=6):
      HAART-naive, CD4+ <500 cells/microl, HIV RNA >10 000 copies/ml; group C (n=3):
      HAART-naive, CD4+ >500 cells/microl, HIV RNA <10000 copies/ml; and group D (n=6):
      HAART, CD4+ <200cells/microl, HIV RNA <80 copies/ml. Tucaresol was added to HAART
      in group A and D patients; group B patients started tucaresol with HAART, group C
      patients received tucaresol alone. Clinical and immunological analyses were
      performed at different time points. RESULTS: Tucaresol-related serious adverse
      events were observed in the first week of therapy in 2/21 patients who were
      viraemic when commencing treatment, but did not occur in patients on stable
      HAART. Tucaresol did not affect HIV viraemia whereas increases in CD4+
      percentages, mainly supported by naive CD4+ cells, were observed. CD8+/28-/45RA+
      cells and HIV-specific CD8+ IFNgamma- and perforin-producing cells improved
      whereas IL-10 mRNA diminished in tucaresol-treated patients. The effects were
      greater with 25 mg given every other day for 1 week. CONCLUSION: In HAART
      receiving patients with proper virus suppression, tucaresol was not associated
      with serious adverse events and resulted in qualitative and quantitative
      stimulation of HIV-specific cytotoxic T lymphocyte activity and generation of
      naive T cells. These data may support further exploration of tucaresol use in
      reconstitution of immune system parameters in HIV patients with proper virus
      suppression while on HAART.

PMID- 15456093
TI  - Salvage therapy with amprenavir, lopinavir and ritonavir 200 mg/d or 400 mg/d in
      HIV-infected patients in virological failure.
AB  - OBJECTIVES: To compare the antiviral efficacy of a salvage therapy combining
      lopinavir and amprenavir with 200 mg/d or 400 mg/d ritonavir, together with
      nucleoside reverse transcriptase inhibitors, over a 26-week period in HIV
      infected patients in whom multiple antiretroviral regimens had failed. DESIGN:
      Phase IIb, randomized, open-label, multicentre trial. Patients were eligible if
      they had <500 CD4+ cells/mm3 and >4 log10 copies/ml HIV-RNA after treatment with
      at least two protease inhibitors (PIs) and one non-nucleoside reverse
      transcriptase inhibitor. RESULTS: At baseline (n=37), the median CD4+ cell count
      was 207/mm3 and the median plasma HIV-1 RNA level was 4.7 log10 copies/ml; the
      median number of PI mutations was seven and the median decrease in phenotypic
      susceptibility to lopinavir and amprenavir was 9.7 and 2.6, respectively. The
      mean number of antiretrovirals received prior to randomization was 7.7. The fall
      in the median HIV-1 RNA level at week 26 was -1.4 log10 copies/ml in the 200 mg/d
      ritonavir group and -2.5 log10 copies/ml in the 400 mg/d group (P=0.02). Viral
      load fell below 50 copies/ml in 32% and 61% of patients, respectively (P=0.07).
      After adjustment for the ritonavir dose, a smaller number of PI mutations was the
      only baseline characteristic associated with a better virological response at
      week 26. Amprenavir concentrations were significantly lower in presence of
      lopinavir. The lopinavir inhibitory quotient at week 6 correlated weakly with the
      change in the HIV-RNA level at week 26. CONCLUSION: Combination of amprenavir,
      lopinavir and 400 mg/d ritonavir shows significant virological efficacy without
      increased toxicity in HIV-infected patients in whom multiple antiretroviral
      regimens have failed.

PMID- 15456094
TI  - Use of pegylated interferons is associated with an increased incidence of
      infections during combination treatment of chronic hepatitis C: a side effect of
      pegylation?
AB  - Standard interferon treatment is known to increase the risk of infections; this
      risk also needs to be evaluated in clinical practice for pegylated interferon. To
      this end, we studied 255 patients treated with standard (103) or pegylated (152)
      interferon, in combination with ribavirin, for hepatitis C. Overall, 31 anti
      hepatitis C virus treatment-related infections were observed. Neutropenia
      (neutrophil counts below 1x10(3) cells/ml) was observed in a significantly higher
      proportion of patients treated with pegylated interferons (48% vs 9%; P=0.0009).
      Of the 31 infections, eight were respiratory infections and were observed only in
      patients with neutropenia. None of the non-respiratory infections was observed in
      patients with neutropenia. Multivariate analysis, using Cox's proportional
      hazards regression model, found a higher risk of all infections associated with
      both use of pegylated interferons [hazard ratio (HR) 4.6] and neutropenia (HR
      2.46). However, neutropenia was independently associated with acute respiratory
      infections only and use of pegylated interferons with non-respiratory infections.
      In summary, use of pegylated interferon appears to increase the risk of non
      respiratory infections independently from neutropenia.

PMID- 15456095
TI  - HIV cohort collaborations: proposal for harmonization of data exchange.
AB  - HIV cohort studies have provided useful information on the natural history of HIV
      infection and the effects of antiretroviral therapy. It has become increasingly
      common to combine data from several cohorts into one dataset in order to address
      certain specific questions with more statistical power than can be achieved with
      the individual studies. This requires each cohort to map data into a standard
      format before merging. Until recently, this standard format has differed for each
      such collaborative analysis. We have therefore developed the HIV Cohort Data
      Exchange Protocol (HICDEP), which is freely available at
      http://www.cphiv.dk/HICDEP.pdf. Once individual cohorts have set up a means of
      transfering data into this format, as and when required, this should greatly
      facilitate data merging for future joint analyses. The HICDEP incorporates data
      from HIV drug resistance tests, which have been particularly challenging for
      cohorts to integrate into databases.

PMID- 15456096
TI  - Selection of K65R mutation in HIV-2-infected patients receiving tenofovir
      containing regimen.

PMID- 15456097
TI  - [Possibilities of surgical treatment of upper cervical spine in patients with
      rheumatoid arthritis].
AB  - PURPOSE OF THE STUDY: Patients with rheumatoid arthritis (RA) often suffer from
      instability of the upper cervical spine. The most common instability is anterior
      atlanto-axial subluxation (AAS). Instability may lead to neurologic deficits from
      spinal cord compression and intractable pain, decreasing quality of life and its
      length. MATERIAL AND METHODS: This prospective study analyzed different fixation
      methods and the influence of atlanto-axial and occipito-cervical fusion on
      clinical and radiological outcome. 41 patients with RA with instability of the
      upper cervical spine were treated surgically for progressive instability, pain
      and neurological deficit. Average age of our patients was 52.4 years (21-76
      years). At the time of surgery, duration of the disease was in average 18.6 years
      (2-47 years). Patients had advanced stage of the disease according to
      Steinbroker, on hands stage 3.7 and feet stage 2.9. Atlanto-axial fixation was
      done for AAS in 27 (24 Magerl transarticular fixations and Brooks-Jenkins
      technique in 3 patients). Occipito-cervical fusion was done in 13 patients (3
      with Ransford loop and sublaminar wires and 9 with CerviFix). One patient was
      managed in halo-cast fixation. Spinal fusion was performed in all patients using
      autologenous bone graft. Patients were evaluated by using Functional Rating Index
      (FRI), Health Assessment Questionnaire (HAQ) and visual pain analogue scale (VAS)
      before and after surgery in set intervals, when radiological examination was also
      performed including dynamic films. RESULTS: Three patients died in the
      postoperative period (3 weeks, 11 and 18 months). 38 patients remained for follow
      up, which was in average 28.4 months. Fusion was considered when hardware was
      intact and patient was satisfied, no motion was detected on dynamic X rays or
      bony fusion was clearly visible. Fusion was assessed in 40 patients, 32 fused, 8
      had fibrous non-union. 3 of these patients had hardware failure. 9 patients had
      preoperatively verified panus formation peridentally, which resorbed after the
      surgery. FRI evaluation was done in 40 patients, 30 improved (14 patients by more
      than 10 points), 6 patients did not change and 4 worsened. The improvement after
      3 and 12 months was statistically significant (p < 0.001). Average HAQ score
      decreased after surgery, but the change was not statistically significant (p >
      0.05). Average VAS score decreased significantly after surgery (p < 0.05). There
      were 5 hardware related complications including one vertebral artery injury. None
      of these complications required subsequent surgery nor had any influence on good
      clinical outcome. DISCUSSION: Results of FRI and VAS show the benefit from early
      indication of surgical stabilization of upper cervical spine in patients with RA.
      Based on our experience, as well as other authors, fixation of AAS by
      transarticular screw fixation according to Magerl is the preferred method in the
      younger patient group. Once destruction of the atlanto-axial joints, lateral
      subluxation or cranial migration of the dens is present, occipito-cervical fusion
      using titanium malleable implant (CerviFix) is necessary. CONCLUSION: Positive
      clinical outcomes advocate early surgical intervention as described in recent
      literature. Surgery prevents subsequent neurological damage life quality
      deterioration and shortening of life expectancy.

PMID- 15456098
TI  - [Incorporation of bone allografts with the use of Octopus revision system in
      total hip arthroplasty].
AB  - PURPOSE OF THE STUDY: The study describes the revision arthroplasty of hip joints
      with grade III acetabular defects, as rated according to Paprosky, employing
      morsellized bone allografts and the Octopus revision acetabular system. MATERIAL:
      In the period from 1998 to 2002, a total of 8297 operations were performed in our
      Department; of these 1527 (18.4%) were total hip replacements. In this group, 267
      (15.5%) revision arthroplasties were carried out, with the the Octopus revision
      system being used in 32 patients (age range, 30 to 79 years; average age, 60.3
      years). The average period between the initial surgery and reimplantation was 6.5
      (range, 2-14) years. METHODS: Acetabular defects were filled with morsellized
      cancellous bone allografts (one to three femoral heads per patient) obtained from
      the tissue bank. In nine patients, allografts were combined with hydroxypatite
      (Biovan). Osteointegration of the bone allografts and, if it occurred, loosening
      of the implant were checked by X-ray examination. RESULTS: The patients were
      examined at intervals of two months. The average Harris hip score was 76 points
      at 1 to 3 years. None of the patients had deep post-operative wound infection; in
      one patient, the distal hook of the Octopus system broke off. The complete
      incorporation of allografts was seen on X-ray images in 28 patients; at follow
      up, a radiolucent zone between the acetabular bed and the allograft was still
      visible in four patients. No implant loosening was recorded. DISCUSSION: The
      Octopus system has an advantage of using morsellized allografts instead of solid
      ones that are associated with poorer incorporation and a higher risk of
      loosening. The remodeling of an allograft below the ring leads to the production
      of bone tissue, which is useful if revision arthroplasty were to be performed.
      CONCLUSION: Based on their experience, the authors regard the Octopus revision
      system with the use of morsellized bone allografts from the tissue bank as an
      effective surgical procedure for the treatment of Paprosky grade III acetabular
      defects. The allografts below the ring are fully incorporated and remodeled; as a
      result the initial defect is gradual filling with the patient's own tissue, which
      has very good clinical outcomes.

PMID- 15456099
TI  - [Treatment of juvenile bone cysts by curettage and filling of the cavity with BAS
      0 bioactive glass-ceramic material].
AB  - PURPOSE OF THE STUDY: The aim of the study was to evaluate the long-term results
      of using the bioactive, glass-ceramic material BAS-0 for bone tissue replacement
      after removal of juvenile bone cysts by curettage. MATERIAL: Between 1990 and
      2000, BAS-0 material was used to fill the cavity after removal of a juvenile bone
      cyst in 21 patients, 15 males and 6 females, with an average age of 15 years
      (range 4 to 44 years). Surgical treatment was indicated only in juvenile bone
      cysts meeting the following criteria: 1) subjective complaints, i. e., pain at
      activity; 2) X-ray findings of either a) thinning cortical layer with a potential
      for pathological fracture, particularly in the proximal femur, b) recurrent
      pathological fractures without apparent healing of the cyst or c) increase in
      cyst size by 25% within 6 months. In all patients, the diagnosis of a juvenile
      bone cyst was confirmed by histological examination. Cyst localization was as
      follows: eight in the humerus, eight in the femur, two in the fibula and one in
      the ulna, iliac bone and tibia each. METHODS: After careful curettage of a soft
      tissue lining from the inner surface of the cystic cavity, the space was filled
      completely with 2- to 4-mm BAS-0 granules in 15 patients; in the rest granules
      were applied in a mixture with cancellous bone graft, which was either autologous
      or allogenic. The former was implanted in one patient, the latter, taken from
      either the mother or father, was used in four and one patients, respectively. All
      patients were clinically and radiologically examined during the follow-up period
      of 3 to 12 years, with an average of 7 years. The clinical evaluation was based
      on subjective complaints, and on the state of soft tissues in the region of
      lesion, range of motion in the adjacent joints and the loading capacity of the
      limb treated. Radiological evaluation was based on standard X-ray images assessed
      according to the classification system of Neer. RESULTS: The clinical examination
      showed that 10 patients were free from subjective complaints, one patient had
      rest pain, three patients experienced pain when using the limb, four patients
      reported mild and intermittent pain, two patients were in pain when the whether
      changed and one patient complained of pain during pregnancy. Objectively, no
      inflammatory changes of soft tissues were found. Both passive and active motion
      of the adjacent joints was possible in the full range and the treated limb
      retained its complete function in all patients. X-ray examination showed
      excellent results, i. e., no residuum or cysts recurrence, in 16 patients. A
      residual lesion was present in one patient and cyst recurrence was recorded in
      four patients. DISCUSSION: The currently used methods of treatment include
      corticoid instillation in the cyst, injection of autologous bone marrow, multiple
      drilling and drainage of the cyst and removal of the cyst with subsequent filling
      of the cavity with bone graft. In our patients, the bioactive, glass-ceramic
      material BAS-0 was used to replace either autogenous or allogenic bone grafts.
      Complete healing of the cyst was achieved in 76% of our patients, which is the
      result comparable with the literature data. CONCLUSIONS: Although the therapy of
      juvenile bone cysts has changed from extensive surgical procedures to less
      invasive techniques, the curettage of a cyst with subsequent filling of the
      residual cavity still remains the method of choice in selected patients. Instead
      of autogenous cancellous bone grafts or allogenic grafts predominantly used for
      this procedure, the bioactive, glass-ceramic material BAS-0 can be recommended,
      particularly when the cavity to be filled is located in the metaphysis of a long
      bone, i. e., in the region subject to great compression.

PMID- 15456100
TI  - [Ewing's sarcoma in children--current surgical treatment options, evaluation of
      our patients].
AB  - PURPOSE OF THE STUDY: Neoplastic diseases continue to arouse much concern in the
      general population. This also applies to bone tumors. Until recently, these
      neoplasms, most frequently occurring in children and adolescents, were considered
      to have the worst possible prognosis with a minimal opportunity for a successful
      outcome of treatment. This is a likely reason for the still deeply rooted belief
      that amputation of the affected limb is necessary and disease prognosis is
      uncertain, which also applies to Ewing's sarcoma. Only lately could these
      patients be offered a hope of successful treatment including limb salvage.
      MATERIAL: In the period from 1984 to mid-2003, 78 patients with Ewing's sarcoma
      were treated in our department. Their age ranged from 3 to 25 years, with the
      maximum occurrence between 13 and 17 years. We performed 27 reconstructions, 13
      amputations or exarticulations and 24 resections without replacements. In 13
      patients, the procedure was restricted to diagnostic biopsy only, because the
      tumor was inoperable. METHODS: The diagnosis was made on the basis of diagnostic
      biopsy and, subsequently, neoadjuvant chemotherapy was administered. When this
      resulted in tumor regression, definitive surgery was performed, involving tumor
      resection and bone replacement either with autograft or allograft, or with an
      individual prosthesis. When an implant was not necessary for maintaining limb
      function, a simple resection was carried out. In the patients in whom the tumor
      failed to regress, amputation or exarticulation was inevitable. Inoperable tumors
      were managed by megadose chemotherapy and by radiotherapy. The patients after
      orthopedic surgery receive adjuvant therapy, including bone marrow
      transplantation in indicated cases. RESULTS: The evaluation of our 78 patients
      showed that patient survival is not related to the surgical procedure used. In
      patients with an early diagnosis and a positive response of the tumor to
      chemotherapy, the reconstruction procedure appeared to be sufficiently radical in
      terms of cancer control while preserving limb function; these patients showed
      neither a significant increase in disease recurrence nor metastatic
      dissemination. Similar outcomes were also recorded in patients with a simple
      resection. However, amputation and exarticulation cannot completely be avoided
      and they are necessary in the patients whose tumor failed to respond to
      chemotherapy or in whom radical removal of the tumor is not possible. The poorest
      outcome was recorded in the patients with inoperable tumors, in whom it was not
      possible to carry out a radical orthopedic operation. The time between the onset
      of pain and initiation of therapy is also an important factor affecting the
      treatment outcome. Complications of reconstructive surgery for Ewing's sarcoma
      recorded in our patient group included osteomyelitis and graft fracture in
      addition to relapse and metastatic dissemination followed by death. DISCUSSION:
      Reconstructive surgery for Ewing's sarcoma is carried out in our department in
      patients with a confirmed diagnosis, in whom neoadjuvant therapy has resulted in
      tumor regression and in whom the extent and site of a tumor permit this sort of
      procedure. If this is not possible, limb amputation is indicated. If amputation
      is not possible due to tumor localization, megadose chemotherapy is administered.
      The results of long-term survival evaluation of our patients undergoing resection
      and replacement show that the procedure has been sufficiently radical, because no
      local recurrence or metastatic dissemination followed by death were recorded.
      Disease recurrence, death, graft osteomyelitis and fracture of a graft inclusive
      of osteosynthetic material are the complications reported. CONCLUSIONS: This
      study evaluated the current techniques of treating Ewing's sarcoma, with emphasis
      on reconstructive surgery leading to limb salvation and maintenance of its full
      function. The importance of this approach is obvious when we realize that the
      patients are mostly children and adolescents.

PMID- 15456101
TI  - [Fractures of the tibial pylon: treatment options and outcomes].
AB  - PURPOSE OF THE STUDY: Fractures of a tibial pylon are serious problems in
      traumatology. The methods of their therapy have not been unified yet and
      treatment outcomes are not satisfactory. This is often due to extensive
      comminution of the distal tibia, bone defects or a thin coverage of soft tissue.
      The objective of this study is to compare the literature data and, on the basis
      of this and our own experience, to present guidelines for the treatment of
      fractures of tibial pylons. MATERIAL: In the period from 1998 to June 2002, 60
      patients (average age, 42 years) underwent surgery for a fracture of the tibial
      pylon in the Department of Orthopedics, IPVZ, and in the hospital Na Bulovce,
      First Faculty of Medicine, Charles University in Prague. In most of the patients,
      the injury was caused by falling from a height. Thirteen patients failed to turn
      up for follow-up. METHODS: Plate osteosynthesis or MIO, usually combined with
      plaster cast, were used in 42 patients. External fixation, with individual screws
      or Kirschner's wires in some cases, was employed in 18 patients. External
      fixation was applied in open fractures and in serious comminutions of the distal
      tibia. RESULTS: A total of 47 patients were followed up for a period of 6 months
      to 5 years. Infectious complications occurred in 12 patients (20%), of whom five
      had to undergo repeat surgery. Twenty-five patients (53%) reported good results
      of treatment, with no or only very minor restriction of motion in the ankle
      joint. In 13 patients, the outcome was satisfactory and nine patients were not
      satisfied because of serious restriction of motion or ankylosis of the ankle
      joint. Three patients underwent a delayed arthrodesis of the ankle joint. The
      fractures healed completely in all patients. DISCUSSION: The results achieved in
      our patients were comparable with those described in the international
      literature. The very good and satisfactory outcomes in 53% and 28% of the
      patients, respectively, are in agreement with the studies reporting good rates of
      success. Also the number of infectious complications (20%; 8% serious) was in the
      range generally reported. The initial method of treating fractures of the tibial
      pylon by plate osteosynthesis has gradually been abandoned. The major prognostic
      factors for the outcome of treatment are the extent of injury to soft tissues and
      the kind of surgical procedure used. Therefore, it appears that external
      fixation, usually in combination with semi-closed reduction and fixation of
      fragments with screws and Ki-wires, has a better prognosis not only in open
      fractures but also in closed comminuted fractures with seriously injured soft
      tissues. CONCLUSIONS: Fractures of the tibial pylon are serious injuries and
      their therapy requires good experience in the field and appropriate technical
      facilities. The method of treatment should be chosen according to not only
      fracture type but also soft tissue involvement and the patient's overall state.

PMID- 15456102
TI  - [Complications and risks associated with an anticoagulation therapy combining low
      molecular weight heparin and Warfarin after total replacement of large joints-
      our experience].
AB  - PURPOSE OF THE STUDY: This study deals with the efficacy and safety of
      anticoagulation therapy, using a combination of low molecular weight heparin
      (LMWH) and Warfarin, administered after total arthroplasty (TA) of large joints.
      Patients with a high rate of complications due to bleeding comprised the first
      evaluated group. After the causes had been analyzed and eliminated (or reduced),
      the second group of patients was evaluated. The aim of the study was to ascertain
      whether risks and complications did not overweight the benefits of Warfarin
      administration in the prophylaxis of deep venous thrombosis (DVT) and whether
      this combined anticoagulation therapy, which is cheaper than LMWH alone, was
      generally applicable. MATERIAL: Group 1 comprised 100 consecutive patients
      undergoing surgery in 2001. Group 2 consisted of 122 consecutive patients
      operated on in 2002. Only patients with elective either total knee or hip
      arthroplasties were included. In all of them, Warfarin therapy was initiated at 2
      days after surgery and preoperative LMWH administration was carried on until 6 to
      7 days postoperatively. METHODS: Both groups were examined for the frequency and
      extent of postoperative hematomas, INR (international normalized ratio)
      fluctuation at the time of Warfarin initiation and during its long-term
      administration, and thrombotic and bleeding complications associated with
      anticoagulation therapy. The results were statistically evaluated and compared
      between the groups, and conclusions were drawn for further treatment policy.
      RESULTS: In group 1, 20% of hospitalized patients and 21% within 10 weeks of
      discharge from hospital experienced bleeding or thrombotic complications. A
      markedly high INR at Warfarin initiation was found in 8% of the patients. After
      discharge, 11% were not followed up, 5% were found underdosed and 12% overdosed.
      In group 2, 3.2% of the patients had bleeding complications during
      hospitalization, but no thrombotic events occurred; at 10 weeks of follow-up,
      bleeding or thrombotic complications were recorded in 10.6% of the patients.
      Extreme values of INR at Warfarin initiation were found in 5.7% of the patients.
      After discharge, 5% were not followed up, 30% were found underdosed and 8.1%
      overdosed. The distinctly better results in group 2 were attributed to the
      measures taken to eliminate most of the factors increasing hazards of Warfarin
      anticoagulation therapy, i. e., pre-operative administration of non-steroid
      antirheumatic drugs (NSA), high initial Warfarin doses, strict requirement for
      INR values in the range of 2-2.5, failure to keep the recommended diet after
      discharge, poor compliance with taking the prescribed Warfarin dose and
      insufficient INR monitoring by general practitioners. DISCUSSION: In patients
      undergoing total arthroplasty of large joints, the authors compare the
      anticoagulation therapy based on LMWH and Warfarin with other treatments for DVT
      prevention in terms of efficacy, safety and economy. They prefer LMWH
      administration as early as 12 h before surgery. Although Warfarin administration
      has proved a safe therapy with regard to bleeding complications in a number of
      conditions, this is not the case in patients undergoing total knee or hip
      replacements. These procedures result in great stress for the organism,
      particularly after long-term preoperative NSA treatment, and this is associated
      with a risk of gastric ulcer development or manifestation of existing mucosal
      lesions. The risk of bleeding may be increased by unexplained fluctuation of INR
      values at Warfarin initiation. CONCLUSIONS: The results of this study suggests
      that correctly administered, preventive drug treatment of thromboembolic events
      is an important adjunct to other measures, such as early rehabilitation including
      standing and walking, compression of the lower extremities or sufficient liquid
      intake, taken to prevent the development of deep venous thrombosis. The
      combination of LMWH with Warfarin was used as an anticoagulation therapy in this
      study. The effective and safe Warfarin treatment should be based on the
      experience of an attending physician, who starts and monitors the therapy.
      Warfarin administration requires careful and relatively complex follow-up, with
      frequent INR check-ups. However, the use of appropriate dosage and thorough
      follow-up do not make Warfarin administration completely safe in all cases. For
      instance, a high INR value at Warfarin initiation, which is difficult to
      influence, carries a high risk of bleeding for patients with occult
      gastrointestinal lesions. The authors do not routinely use preventive treatment
      with LMWH alone, primarily for its high cost.

PMID- 15456103
TI  - [Results of Menon's arthroplasty in basal joint osteoarthritis].
AB  - PURPOSE OF THE STUDY: Osteoarthritis of the basal joints is a frequent
      degenerative disease. The wide range of arthritic lesions of the first carpal
      metacarpal joint should be treated by targeted surgical techniques. These
      methods, including arthroplasty, arthrodesis and alloplasty, for use in relevant
      indications are available in the Department of Orthopedics at the Medical Faculty
      Teaching Hospital in Hradec Kralove. In this study, the results of Menon's
      arthroplasty modified by the authors are evaluated. MATERIAL AND METHODS: The
      interpositional arthroplasty, first used and published by Menon in 1955, was
      introduced in January 2002 by the authors in the treatment of arthritic lesions,
      classified as stage III disease by the Eaton radiological rating system, in
      middle-aged, manually working women. The procedure consists of resection of the
      trapezium articular surface affected by osteoarthritis, tendon interposition, and
      the reconstruction of the articular capsule soft tissues using tenodesis of the
      abductor pollicis muscle tendons. Sixteen female patients were treated by our
      modified technique. The post-operative outcome of arthroplasty was evaluated by
      comparison of both hands' efficiency, with the use of the Cooney score system.
      RESULTS: At 2 years of follow-up, in 14 treated hands there was pain relief,
      improved mobility and an increase in grip strength; excellent and very good
      outcomes, as evaluated by the Cooney score, were achieved in 80% of the operated
      hands. In one patient, conversion of Menon's arthroplasty to an alloplasty with a
      Rubena prosthesis had to be carried out due to persistent complaints. DISCUSSION:
      The authors evaluate the surgical procedure used and present the reasons for
      their modification of the Menon's technique with the use of the long palmar
      muscle tendon. The choice of operative techniques for specific indications, as
      available in the authors' department, is discussed. The outcomes reported in this
      study are compared with the results published in the foreign literature.
      Complications and risks of this treatment are mentioned. The advantage of a
      partial over a total trapeziectomy is emphasized. CONCLUSIONS: The early outcomes
      of Menon's arthroplasty, which was indicated in manually working, middle-age
      female patients with stage III basal-joint osteoarthritis, are satisfactory. This
      precisely indicated and correctly performed technique has so far fulfilled the
      authors' expectations.

PMID- 15456104
TI  - Covariates and random effects in a gamma process model with application to
      degradation and failure.
AB  - The gamma process is a natural model for degradation processes in which
      deterioration is supposed to take place gradually over time in a sequence of tiny
      increments. When units or individuals are observed over time it is often apparent
      that they degrade at different rates, even though no differences in treatment or
      environment are present. Thus, in applying gamma-process models to such data, it
      is necessary to allow for such unexplained differences. In the present paper this
      is accomplished by constructing a tractable gamma-process model incorporating a
      random effect. The model is fitted to some data on crack growth and corresponding
      goodness-of-fit tests are carried out. Prediction calculations for failure times
      defined in terms of degradation level passages are developed and illustrated.

PMID- 15456105
TI  - Ascertainment-adjusted maximum likelihood estimation for the additive genetic
      gamma frailty model.
AB  - The additive genetic gamma frailty model has been proposed for genetic linkage
      analysis for complex diseases to account for variable age of onset and possible
      covariates effects. To avoid ascertainment biases in parameter estimates,
      retrospective likelihood ratio tests are often used, which may result in loss of
      efficiency due to conditioning. This paper considers when the sibships are
      ascertained by having at least two affected sibs with the disease before a given
      age and provides two approaches for estimating the parameters in the additive
      gamma frailty model. One approach is based on the likelihood function
      conditioning on the ascertainment event, the other is based on maximizing a full
      ascertainment-adjusted likelihood. Explicit forms for these likelihood functions
      are derived. Simulation studies indicate that when the baseline hazard function
      can be correctly pre-specified, both approaches give accurate estimates of the
      model parameters. However, when the baseline hazard function has to be estimated
      simultaneously, only the ascertainment-adjusted likelihood method gives an
      unbiased estimate of the parameters. These results imply that the ascertainment
      adjusted likelihood ratio test in the context of the additive genetic gamma
      frailty may be used for genetic linkage analysis.

PMID- 15456106
TI  - Accelerated rates regression models for recurrent failure time data.
AB  - In this article, we formulate a semiparametric model for counting processes in
      which the effect of covariates is to transform the time scale for a baseline rate
      function. We assume an arbitrary dependence structure for the counting process
      and propose a class of estimating equations for the regression parameters.
      Asymptotic results for these estimators are derived. In addition, goodness of fit
      methods for assessing the adequacy of the accelerated rates model are proposed.
      The finite-sample behavior of the proposed methods is examined in simulation
      studies, and data from a chronic granulomatous disease study are used to
      illustrate the methodology.

PMID- 15456107
TI  - Modelling converging hazards in survival analysis.
AB  - The Cox proportional hazards model has become the standard model for survival
      analysis. It is often seen as the null model in that "... explicit excuses are
      now needed to use different models" (Keiding, Proceedings of the XIXth
      International Biometric Conference, Cape Town, 1998). However, converging hazards
      also occur frequently in survival analysis. The Burr model, which may be derived
      as the marginal from a gamma frailty model, is one commonly used tool to model
      converging hazards. We outline this approach and introduce a mixed model which
      extends the Burr model and allows for both proportional and converging hazards.
      Although a semi-parametric model in its own right, we demonstrate how the mixed
      model can be derived via a gamma frailty interpretation, suggesting an E-M
      fitting procedure. We illustrate the modelling techniques using data on survival
      of hospice patients.

PMID- 15456108
TI  - A cautionary note on the use of the Gronnesby and Borgan goodness-of-fit test for
      the Cox proportional hazards model.
AB  - Gronnesby and Borgan (1996, Lifetime Data Analysis 2, 315-328) propose an omnibus
      goodness-of-fit test for the Cox proportional hazards model. The test is based on
      grouping the subjects by their estimated risk score and comparing the number of
      observed and a model based estimated number of expected events within each group.
      We show, using extensive simulations, that even for moderate sample sizes the
      choice of number of groups is critical for the test to attain the specified size.
      In light of these results we suggest a grouping strategy under which the test
      attains the correct size even for small samples. The power of the test statistic
      seems to be acceptable when compared to other goodness-of-fit tests.

PMID- 15456109
TI  - Likelihood-based inference for the shape parameter of a two parameter Weibull
      distribution.
AB  - Based on a Type 2 censored sample, we use the likelihood-based approach to draw
      likelihood inference on the shape parameter gamma of a two-parameter Weibull
      distribution. In particular, we derive the profile, conditional and marginal
      likelihoods of gamma. Numerical results along with some concluding remarks
      regarding the use of likelihood-based methods for inference are provided.

PMID- 15456110
TI  - How family physicians can help spread 'the heart truth'.

PMID- 15456111
TI  - Treatment of post-traumatic stress disorder can be complex.

PMID- 15456112
TI  - AFP policy on using generic and brand names for drugs.

PMID- 15456113
TI  - Learning deficits may account for cases of school phobia.

PMID- 15456114
TI  - The importance of having health insurance and a usual source of care.

PMID- 15456115
TI  - Asthma update: Part II. Medical management.
AB  - The National Asthma Education and Prevention Program recently updated its
      guidelines for the management of asthma. An evidence-based approach was used to
      examine several key issues regarding appropriate medical therapy for patients
      with asthma. The updated guidelines have clarified these issues and should alter
      the way physicians prescribe asthma medications. Chronic inhaled corticosteroid
      use is safe in adults and children, and inhaled corticosteroids are recommended
      as first-line therapy in adults and children with persistent asthma, even if the
      disease is mild. Other medications, such as cromolyn, theophylline, and
      leukotriene modifiers, now are considered alternative treatments and should have
      a more limited role in the management of persistent asthma. The addition of a
      long-acting beta2 agonist to an inhaled corticosteroid is superior to all other
      combinations as well as to higher dosages of inhaled corticosteroids alone.
      Combination therapy with an inhaled corticosteroid and a long-acting beta2
      agonist is the preferred treatment for adults and children with moderate to
      severe asthma. Antibiotic therapy offers no additional benefit in patients with
      asthma exacerbations.

PMID- 15456116
TI  - Management of normal pressure hydrocephalus.
AB  - Gait instability, urinary incontinence, and dementia are the signs and symptoms
      typically found in patients who have normal pressure hydrocephalus. Estimated to
      cause no more than 5 percent of cases of dementia, normal pressure hydrocephalus
      often is treatable, and accurate recognition of the clinical triad coupled with
      radiographic evidence most commonly identifies likely responders. Magnetic
      resonance imaging or computed tomography typically demonstrates ventricular
      dilation with preservation of the surrounding brain tissue. The abnormality in
      normal pressure hydrocephalus occurs secondary to an abnormality in fluid
      removal, leading to an increase in ventricular size and encroachment of enlarged
      ventricles on adjacent brain tissue. The pressure exerted on the cerebral
      parenchyma by immense fluid-filled cavities deforms white matter tracts,
      instigating gait abnormalities and incomplete control of the bladder, as well as
      difficulties in processing incoming stimulation and in producing expeditious
      responses. Signs and symptoms often occur as sequelae to an imbalance between the
      expected ongoing production of cerebrospinal fluid and continuous efflux.
      Ventriculoperitoneal shunting is used to relieve excess ventricular fluid not
      absorbed by normal physiologic channels. Multiple studies have explored various
      techniques to identify patients with normal pressure hydrocephalus in an effort
      to predict likely benefit from shunting. However, the effectiveness of
      cerebrospinal fluid diversion has never been proven in a randomized controlled
      trial comparing use of a shunt versus no shunt.

PMID- 15456117
TI  - Normal pressure hydrocephalus: what it is and how it is treated.

PMID- 15456118
TI  - Clinical practice guidelines for chronic kidney disease in adults: Part II.
      Glomerular filtration rate, proteinuria, and other markers.
AB  - The Kidney Disease Outcome Quality Initiative of the National Kidney Foundation
      published clinical practice guidelines on chronic kidney disease in February
      2002. Of the 15 guidelines, the first six are of greatest relevance to family
      physicians. Part II of this two-part review covers guidelines 4, 5, and 6.
      Glomerular filtration rate is the best overall indicator of kidney function. It
      is superior to the serum creatinine level, which varies with age, sex, and race
      and often does not reflect kidney function accurately. The glomerular filtration
      rate can be estimated using prediction equations that take into account the serum
      creatinine level and some or all of specific variables (age, sex, race, body
      size). In many patients, estimates of the glomerular filtration rate can replace
      24-hour urine collections for creatinine clearance measurements. Urine dipsticks
      generally are acceptable for detecting proteinuria. To quantify proteinuria, the
      ratio of protein or albumin to creatinine in an untimed (spot) urine sample is an
      accurate alternative to measurement of protein excretion in a 24-hour urine
      collection. Patients with persistent proteinuria have chronic kidney disease.
      Other techniques for evaluating patients with chronic kidney disease include
      examination of urinary sediment, urine dipstick testing for red and white blood
      cells, and imaging studies of the kidneys (especially ultrasonography). These
      techniques also can help determine the underlying cause of chronic kidney
      disease. Family physicians should weigh the value of the National Kidney
      Foundation guidelines for their clinical practice based on the strength of
      evidence and perceived cost-effectiveness until additional evidence becomes
      available on the usefulness of the recommended quality indicators.

PMID- 15456119
TI  - Efficient identification of adults with depression and dementia.
AB  - Family physicians must decide how to screen for depression or dementia and which
      patients to screen. Mental health questionnaires can be helpful. In practice
      based screening, questionnaires are administered to all patients, regardless of
      risk status. In case-finding screening, questionnaires are administered only when
      depression or dementia is suspected. The 2002 U.S. Preventive Services Task Force
      report recommends screening adults for depression to improve detection and
      patient outcomes but does not suggest the use of any particular screening
      instrument. Serial or sequential testing with the Patient Health Questionnaire-2
      and the Patient Health Questionnaire-9 is a good strategy for detecting major
      depressive episodes in primary care settings. The Patient Health Questionnaire-2
      consists of two questions that assess the presence of anhedonia and dysphoria. If
      a patient answers "yes" to either question, the more specific Patient Health
      Questionnaire-9 is administered to assess the severity of depressive symptoms and
      to ascertain the presence of major depressive episode. The Patient Health
      Questionnaire-9 also can be used to monitor symptom severity and treatment
      response. The 2003 U.S. Preventive Services Task Force report does not recommend
      for or against routine screening for dementia in older adults. However, the
      report does assert that cognitive function should be assessed when impairment is
      suspected. The Folstein Mini-Mental State Examination and the Functional
      Activities Questionnaire are suggested tools. The Clock Drawing Test also has
      been shown to be useful in primary care settings.

PMID- 15456120
TI  - Blisters. Bullae secondary to edema.

PMID- 15456121
TI  - Key system changes to boost practice production and profitability.
AB  - A dentist may find many ways to increase dental practice production and
      profitability. One of the best ways is to focus on comprehensive diagnosis and
      treatment, but this must be accompanied by a reorganization of the practice's
      scheduling systems. In no way am I suggesting that practices only perform large
      cases because this is unrealistic for most offices. However, Levin Group data
      indicates that 81% of all dental appointments are single-tooth treatment. By
      working to reduce this to approximately 55% to 60%, the practice will notice an
      immediate increase in production. This increase will be based on a new focus on
      comprehensive diagnosis and treatment. This focus will allow the practice to
      offer a broader array of need-based and elective services and an increased
      capability in the areas of case presentation. Any practice can take advantage of
      this methodology and gain a significant benefit in only 1 year.

PMID- 15456122
TI  - The biologic objectives of root canal therapy: meeting the standard.
AB  - A comprehensive preoperative evaluation of the basic endodontic principles
      outlined in this article is consistent with more long-term clinical success.
      Adherence to these principles may help further define the standard of endodontic
      care.

PMID- 15456123
TI  - Composite tints: mixing composite materials to alter color and techniques to
      simulate hypocalcification and craze lines.
AB  - The purpose of this article is to teach advanced composite techniques based on
      sound material science and advanced artistic principles. The effects of oxygen
      inhibition, shrinkage, wear, filler content, and composite chemistry are
      reviewed. Color blending using composite translucency to show through underlying
      and surrounding tooth structure achieves improved color matching and color
      transition from tooth structure to a composite restoration. Mixing color tints
      modifies composite color, and applying composite tints produces effects such as
      hypocalcifications and craze lines.

PMID- 15456124
TI  - Sometimes "seeing is believing" just isn't enough.

PMID- 15456125
TI  - Periodontal-endodontic interdisciplinary treatment--a case report.
AB  - Periodontal-endodontic lesions pose a difficult diagnostic and therapeutic
      challenge to the dental practitioner. A careful diagnostic examination consisting
      of a thorough patient and dental history, comprehensive clinical examination, and
      use of appropriate dental radiographs is necessary to arrive at a proper
      diagnosis of the periodontal-endodontic lesion. Despite these measures, it is not
      always possible to make an accurate diagnosis, which is imperative to provide the
      proper therapy in the correct treatment sequence. In some instances, endodontic
      or periodontal therapy alone may suffice; however, in other instances, a
      combination of endodontic and periodontal therapy may be required to successfully
      treat the case. In this article, classifications of periodontal-endodontic
      lesions are discussed, including the appropriate treatment and correct treatment
      sequence for each classification. Prognosis of periodontal-endodontic lesions
      depends on the diagnosis, treatment, and chronicity of the lesion, as well as the
      duration of periodontal involvement. A clinical case is presented in which a
      periodontal endodontic lesion has been successfully treated with a combination of
      conventional endodontic therapy and regenerative periodontal surgery.

PMID- 15456126
TI  - Handpiece technology and concepts 125 years later.

PMID- 15456127
TI  - Closed-flap laser-assisted esthetic dentistry using Er:YSGG technology.
AB  - Use of a hard-/soft-tissue laser is a wonderful adjunctive tool for esthetic and
      restorative dentistry. The cases described here demonstrate some of the many ways
      in which this laser technology allows clinicians to make significant soft- and
      hard-tissue changes. These changes not only improve the final esthetic outcome of
      the case but also provide the biologic functional parameters required for
      successful dentistry.

PMID- 15456128
TI  - [Stem cells: properties and perspectives of therapeutic use].
AB  - In the present work, we review the properties of some stem cell types, namely
      embryonic, hematopoietic and mesenchymal stem cells, which present the most
      significant interest for use in medicine. Stem cells are undifferentiated cells
      capable of both self-maintenance and differentiation into mature specialized
      cells. According to their origin, stem cells can be classified as embryonic and
      somatic ones. The first ones can be indefinitely maintained in culture, and
      possess the ability to differentiate into all cells of the adult organism. The
      second ones possess the limited capacity to differentiate and, probably, a
      limited proliferative potential. For therapeutic use, important but hotly debated
      is the plasticity of somatic stem cells, i.e. context-dependent differentiation
      into "non-related" cell types. It is assumed that the differentiation of the
      majority of stem cell types proceeds according to the principle of stepwise
      hierarchical maturation through the stage of intermediate rapidly proliferating
      progenitor cells. The use of stem cells in medicine is mostly at the preclinical
      stage now. Despite the fact that embryonic stem cells are highly promising as
      therapeutic agents, a number of circumstances substantially limits their
      therapeutic use in the near future. At the same time, approaches involving
      autotransplantation of hematopoietic or mesenchymal stem cells are beginning to
      be applied successfully in the clinical trials for treatment of limb ischaemia
      and myocardial infarction. It is clear that despite a large number of problems
      and unsolved questions, the use of stem cells in medicine promises a dramatic
      progress in the treatment of many severe diseases.

PMID- 15456129
TI  - [Bacterial and archaeal S-layers as object of bionanotechnology].
AB  - Many species of Bacteria and Archaea posses a regularly structured surface layers
      (S-layers) as outermost cell envelope component. S-layers composed of a single
      protein or glycoprotein species. The individual subunits of S-layers interact
      with each other and with the supporting bacterial envelope component through non
      covalent forces. Pores in the crystalline protein network are with mean diameter
      of 2-6 nm, the thickness of S-layer is 5-10 nm. The isolated S-layer subunits
      reassemble into two-dimensional crystalline arrays in solution, on solid
      supports, on planar lipid films. These unique features of S-layers have led to a
      broad spectrum applications. This review focuses on the structural properties S
      layers and S-proteins and their applications with accent to using this structures
      in nanobiotechnology.

PMID- 15456130
TI  - [Polymorphism of mitochondrial genome noncoding regions in the three Kazakh
      populations inhabited different areas of Kazakhstan and in the samples of DNA
      from ancient people of Kazakhstan Altai].
AB  - Polymorphism of major noncoding region of mitochondrial DNA (mtDNA D-loop, 528 bp
      in length) from the three modem kazakh populations and from DNA samples of
      ancient people inhabited modern Kazakhstani Altai were studied. PCR and RFLP
      analysis of 13 sites of restriction--BamHI, EcoRV, Sau3AI (1 restriction site),
      KpnI (2 sites), HaeIII (3 sites), RsaI (5 restriction sites), were carried out.
      The distribution of each site frequencies was determined. Nucleotide diversity
      (h) and genetic distance between different kazakh population and other
      populations of world were estimated. The same RFLP analysis of the mitochondrial
      DNA control region was carried out for the paleogenomic samples. It was shown
      that two samples of ancient mitochondrial DNA were monomorphous throughout all
      analyzed restriction sites.

PMID- 15456131
TI  - [Comparative analysis of the hypervariable segment 1 mutational spectra in human
      mitochondrial DNA phylogeographic groups].
AB  - Variability of the mtDNA hypervariable segment 1 (HVS 1) nucleotide sequences
      belonging to 88 phylogeographic clusters characteristic for human populations of
      Africa, West and East Eurasia was analyzed. Statistically significant differences
      between distribution of mutations in mitochondrial gene pools of the human
      continental groups were revealed. The list of the HVS 1 nucleotide positions
      characterizing by instability explained by the model of mtDNA strands dislocation
      during the replication process is suggested. It was shown that DNA strands
      dislocation during mtDNA replication is one of the key mechanisms of the context
      dependent mtDNA mutagenesis during the regional differentiation of human
      populations.

PMID- 15456132
TI  - [Determination of the endonuclease activity encoded by retrotransposon].
AB  - Mobile element Penelope is mobilized in the course of hybrid dysgenesis in D.
      virilis. This element is also responsible for the activation of other unrelated
      families of TE occurring in the progeny of dysgenic crosses. Penelope elements
      have extremely variable structure and combine some properties of LINEs and LTR
      containing elements. Penelope-like elements (PLEs) have been recently described
      in various organisms including fish species, rotifers and amoebae. Computer
      analysis enabled to predict the presence of reverse transcriptase domain in
      Penelope-encoded polyprotein as well as UvrC type endonuclease at the C-end of
      the element. It is noteworthy that none of the previously described retroelements
      was shown to contain such a nuclease. Multiple alignments revealed five
      conservative catalytic motifs and all conservative residues present in GIY-YIG
      endonuclease family within Penelope-encoded protein. Herein we have demonstrated
      that Penelope element isolated from D. virilis encodes functionally active
      endonuclease exhibiting some sequence-specificity to the sequence previously
      demonstrated to serve as Penelope genomic insertion site.

PMID- 15456133
TI  - [Phylogeografic analysis of mitochondrial DNA Nogays: the high level of mixture
      of maternal lineages from Eastern and Western Eurasia].
AB  - Analysis of markers mtDNA in a population of Nogays (n = 206), living on Nothern
      Caucasus and speaking on language of Turkic branch of the Altaic linguistic
      family, has shown, that the level of their genetic differentiation is high (H =
      0.99). Among the found haplotypes there is all the basic Western Eurasian
      haplogroups, most often of which are clusters H (22%) and U (21%), however, the
      percentage of the lineages specific only for populations of East Eurasia (40%) is
      highest. In a population of Nogays there are also variants mtDNA, belonging to
      haplogroup M1, characteristic for North East Africa, and gaplogroup U2, typical
      for populations of India. This testifies about presence in a gene pool of Nogays
      people of components of a various parentage.

PMID- 15456134
TI  - [Alcohol dehydrogenases ADH1B and ADH7 gene polymorphism in Russian population
      from the Siberian region].
AB  - The Allele and genotype didtributions of the two alcohol dehydrogenase genes
      ADH1B (polymorphism A/G in exon 3, detected with restrictase MslI) and ADH7
      (polymorphism G/C in intron 5, detected with restrictase StyI) was studied in
      three Russian populations from the Siberian region. The absence of
      interpopulation and intersexual differences in the allele frequency was
      determined. The allele ADH1B*G (+MslI, A2) was found in low frequency (3.6-7.5%),
      the mutant allele ADH7 (-StyI, B2) frequency in total population (n = 339) was
      46.02%. The genotype distributions of the ADH1B and ADH7 in these populations
      were agreed with the Hardy-Weinberg equilibrium and linkage equilibrium.
      Increased frequency of ADH7 B2 allele was revealed in elder group (after 40
      years) in the total sample and in the Tomsk city inhabitants (n = 113) on 11% (P
      = 0.001) and 9% (P = 0.017) accordingly. ADH7 and ADH1B genes polymorpisms did
      not show association with antioxidant activity, which was determined from the
      blood plasma ability to reduce the yield of products interacting with
      thiobarbituric acid in the lecitin-Fe2+ ions model system. The statistically
      significant decrease of serum very low density lipoproteins (LPVLD) level (on
      9.95%, P = 0.045) and close to statistically significant decrease systolic
      pressure (on 6.80%, P = 0.068) and serum triglycerides level (on 6.16 of %, P =
      0.058) were revealed among the A2 allele ADH1B gene carriers in Tomsk population.

PMID- 15456135
TI  - [Novel site-specific endonucleases F-TflI, F-TflII and F-TflIV encoded by the
      bacteriophage T5].
AB  - Novel site-specific H-N-H endonucleases F-TflI, F-TflII and F-TflIV were
      identified. These endonucleases are encoded by open reading frames localized in
      the bacteriophage T5 tRNA gene region. The endonuclease F-TflIV was shown to
      introduce double-strand break into pseudo palindromic 17 bp DNA sequence yielding
      1 bp extensions with 3'-overhangs. In contrast to F-TflIV, endonucleases F-TflI
      and F-TflII cleave only one strand of their asymmetric divergent DNA substrates.
      Each of these endonucleases introduces interruptions into only the particular
      strand (template or coding). Amino acid sequences of the endonucleases under
      study are highly homologous in the H-N-H motif regions and C-terminal sequences,
      forming putative catalytic domain. Endonuclease F-TflIV N-terminal region is
      homologous to the amino acid sequences representing H-T-H recognition domain
      found in LuxR family transcription regulators. Putative recognition NUMOD4 motif
      characteristic for a number of H-N-H endonucleases was shown to be also present
      in the endonuclease F-TflI and F-TflII N-terminal sequences. Two-domain structure
      was proposed for endonucleases F-TflI, F-TflII and F-TflIV with N-terminal
      recognition domain and C-terminal catalytic domain. A hypothesis of evolutionary
      origin of these endonucleases as a result of catalytic and recognition domains
      recombination was suggested.

PMID- 15456136
TI  - [Molecular analysis of structural abnormalities in papillary thyroid carcinoma
      gene].
AB  - Rearrangements of the RET proto-oncogene (RET/PTC) and BRAF gene mutations are
      the major genetic alterations in the etiopathogenesis of papillary thyroid
      carcinoma (PTC). We have analyzed a series of 118 benign and malignant follicular
      cell-derived thyroid tumors for RET/PTC rearrangements and BRAF gene mutations.
      Oncogenic rearrangements of RET proto-oncogene was revealed by semiquantitative
      RT-PCR of simultaneously generated fragments corresponding to tyrosine kinase
      (TK) and extracellular RET domains. The clear quantitative shift toward the TK
      fragment is indicative for the presence of RET rearrangements. The overall
      frequency of RET/PTC rearrangements in PTC was 14% (12 of 85), including 7
      RET/PTC1, 2 RET/PTC3, 1 deltaRFP/RET and 2 apparently uncharacterized
      rearrangements. The most common T1796A transversion in BRAF gene was detected in
      55 of 91 PTC (60%) using mutant-allele-specific PCR. We also identified two
      additional mutations: the substitution G1753A (E585K) and a case of 12-bp
      deletion in BRAF exon 15. Moreover, there was no overlap between PTC harboring
      BRAF and RET/PTC mutations, which altogether were present in 75.8% of cases (69
      of 91). Taken together, our observations are consistent with the notion that BRAF
      mutations appear to be an alternative pathway to oncogenic MAPK activation in
      PTCs without RET/PTC activation. Neither RET/PTC rearrangements nor BRAF muta
      tions were detected in any of 3 follicular thyroid carcinomas, 11 follicular
      adenomas and 13 nodular goiters. The high prevalence of BRAF mutations and
      RET/PTC rearrangements in PTCs and the specificity of these alterations to PTC
      make them potentially important markers for the preoperative tumor diagnosis.

PMID- 15456137
TI  - [Methylation of the promoter region of the RASSF1A gene, a candidate tumor
      suppressor, in primary epithelial tumors].
AB  - Methylation of the promoter CpG-islands of the candidate tumor suppressor gene
      RASSF1A (3p21.31) was studied in primary tumors of kidney, breast and ovary (172
      cases). Methylation-specific PCR (MSP) and methyl-sensitive restriction
      endonuclease digestion followed by PCR (MSRA) were applied. Statistically
      significant correlation (P << 10(-6)) was shown for the results of the MSP and
      MSRA, and the data of bisulfite sequencing reported earlier. The frequency of
      RASSF1A methylation according to MSP and MSRA was 86% (25/29) and 94% (50/53) in
      renal cell carcinoma (RCC) and 64% (18/28) and 78% (32/41)--in breast carcinoma
      (BC) samples, and 59% (17/29) and 73% (33/45) in ovarian epithelial tumors (OET),
      respectively. The use of several methyl-sensitive restriction enzymes (HpaII,
      HhaI, Bsh12361, AciI) enhanced the sensitivity of MSRA and allowed to analyze
      methylation status of 18 CpG-pairs in the RASSF1A CpG-island. Density of
      methylation of the RASSF1A CpG-island was 72% (644/900) in RCC, 63% (361/576) in
      BC, and 58% (346/594) in OET samples (18 CpG-pairs multiplied to the number of
      samples shown methylation were assumed as 100%). The RASSF1A gene methylation was
      also observed in samples of morphologically normal tissues adjacent to
      corresponding tumors (11-35%), but it was not detected in blood DNAs of healthy
      donors (0/15). The RASSF1A methylation frequency did not show significant
      correlation to tumor stage, grade and metastases (P = 0.3-1.0). The RASSF1A gene
      methylation was observed more frequently than other investigated aberrations-
      hemi- and homozygous deletions inside or around this gene. These observations are
      consistent with the hypothesis that the RASSF1A gene methylation is an early
      event in the carcinogenesis and one of the dominant ways of its inactivation.

PMID- 15456138
TI  - [Localization of DNA sequences tightly associated with synaptonemal complex in
      compositional fractions of golden hamster].
AB  - The synaptonemal complex isolated from the spermatocyte nuclei by exhaustive
      hydrolysis of the latter by DNase II contains tightly associated DNA sequences
      (SCAR DNA). Here we studied the compositional properties of a cloned family of
      SCAR DNA of golden hamster, namely we performed the localization of 27 SCAR DNA
      clones on compositionally fractionated genomic DNA from golden hamster. We
      observed that sequences of the SCAR DNA family are mainly localized in the GC
      poor isochore families L1 and L2, that showed 63% hybridization signals. This
      means that 37% of signals is referred to the GC-rich isochores, indicating the
      presence of SCAR DNA overall the genome, even if each isochore family presents
      differences in density and sequence type. Moreover, the SCAR DNA sequences
      containing regions of homology with LINE/SINE repeats were observed in all the
      isochore families. The compositional localization of SCAR DNA is in agreement
      with the hypothesis that SC and SCAR DNA participate in the chromatin
      organization during the meiosis prophase I, which should result in the attachment
      of chromatin loops to lateral elements of SC along the whole length of the
      latter.

PMID- 15456139
TI  - [Human ribosomal protein S26 inhibits splicing of its own pre-mRNA].
AB  - In vitro splicing was studied for a human ribosomal protein (rp) S26 pre-mRNA
      fragment containing the first exon, first intron, and a part of the second exon.
      Splicing yielded two products, the first was corresponded to a fragment of the
      mature rpS26 mRNA and another was retained the 19 3'-terminal nucleotides of the
      first intron between the first and second exons. Recombinant rpS26 inhibites
      generation of both splicing products in vitro. The inhibition was specific,
      because another recombinant human rp, S19, had no effect on the splicing of the
      pre-mRNA fragment. Toe-printing was used to map the spS26-binding sites of the
      per-mRNA within the regions of the conventional and alternative 3' splicing sites
      of the first intron. On the strength of the rusults, rpS26 was assumed to
      regulate the expression of its own gene at the level of pre-mRNA splicing via a
      feedback mechanism.

PMID- 15456140
TI  - [Large subunit of translation initiation factor--3 p170 contains potentially
      functional nuclear localization signals].
AB  - Eukaryotic translation factors and their subunits can have independent cellular
      functions, including regulation of nuclear events. We analyzed primary structure
      of p170 large subunit of human translation initiation factor eIF3 and found four
      potential bipartite nuclear localization signals (NLS). Then we studied whether
      these NLS were functional, that is were able to direct protein to cell nucleus.
      Complementary DNA of p170 fragments were expressed in cultured CV-1 and Cos-1
      green monkey cells, and localization of fused with GFP proteins was determined by
      fluorescent microscopy. We established that p170 molecule possessed at least two
      functional NLS which determined nuclear localization of p170 fragments. At the
      same time more long p170 fragments containing the same functional NLS could be
      retained in cytoplasm. We speculate that either using specific factors or after
      limited proteolysis p170 can enter cell nucleus and participate in genome
      expression regulation. Also we do not exclude the possibility that functioning of
      p170 in cytoplasm can be regulated by reversible binding of importins to its NLS.

PMID- 15456141
TI  - [Conformational properties of neuromedin NmU-8 and its modified analogs].
AB  - The comparative study of the spatial organization and conformational properties
      of NmU-8 neuropeptide and its modified analogs with available experimental data
      has been carried out. The effect of amino acids point mutation on conformational
      states of native neuropeptide has been discussed. The low-energy conformations
      responsible for neuropeptide contractile activity was revealed.

PMID- 15456142
TI  - [The effect of Ca2+ ions on DNA compaction in the complex with non-histone
      chromosomal protein HMGB1].
AB  - The analysis of absorption and circular dichroism spectra in UV and IR regions
      showed that Ca2+ ions interact both with the phosphate groups of DNA and with the
      HMGB1 protein. Not only negatively charged C-terminal part of the protein
      molecule participates in interaction with metal ions but also its DNA-binding
      domains. The latter fact leads to the change of the mode of protein-DNA
      interaction. The presence of Ca2+ ions prevents formation of ordered
      supramolecular structures, specific for the HMGB1-DNA complexes, though promotes
      intermolecular aggregation. The structure of the complexes between DNA and the
      protein HMGB1 lacking C-terminal tail appears to be the most sensitive to the
      presence of Ca2+ ions. The data obtained allow to conclude that Ca2+ ions do not
      play a structural role in the HMGB1/DNA complexes and the presence of these ions
      is not necessary to DNA compaction in such systems.

PMID- 15456143
TI  - [Construction of pMH, a convenient Escherichia coli protein expression vector].
AB  - Here we describe the construction of a new vector, pMH, designed for protein
      expression in E. coli. The vector provides inducible and powerful T7 RNA
      polymerase driven transcription of the sequences introduced, and a polylinker
      comprising now 10 most widely used restriction sites, which allows virtually any
      sequence to be cloned. Cloning in-frame with the N-terminal (c-myc)3-(His)6-tag
      makes it possible, first, to easily affinity purify the proteins being expressed
      and, second, to detect the recombinant proteins with the antibodies specific for
      any of the tags when protein-specific antibodies are unavailable. General utility
      of pMH was demonstrated by successful expression in E. coli and further
      purification of Drosophila melanogaster Chriz (CG10712) product and of a number
      of its C-terminal truncations, with the approximate protein yeild constituting 10
      mg/l culture.

PMID- 15456144
TI  - [Biosynthesis of recombinant human hepatitis B M-HBsAg in silkworm larvae].
AB  - The middle surface antigen (M-HBsAg) of human hepatitis B virus is virus envelope
      protein. It's used as a basis for development of vaccine and test-system for
      detecting of hepatitis B virus. The cDNA of M-HBsAg was inserted into transfer
      vector pBK273 under the polyhedron promoter with obtaining of recombinant plasmid
      DNA pBHep-2. As a result of cotransfection pBHep-2 with wild type BmNPV the
      recombinant baculovirus rBmNPVHep which included the cDNA of M-HBsAg under the
      polyhedron promoter was obtained. Infection of silkworm larvae Bombyx mori with
      recombinant virus resulted in expression of foreign gene and accumulation of
      middle surface antigen of human hepatitis B virus mostly (>90%) in fat bodies of
      silkworm larvae.

PMID- 15456145
TI  - [Antibodies to DNA in the blood of patients with tick-borne encephalitis].
AB  - A comparison of relative levels of autoantibodies (Abs) to both native (n) and
      denatured (d) DNA in the blood of 55 patients with tick-borne encephalitis (TBE)
      was carried out. 31% of patients with TBE was shown to have an increased level
      Abs to nDNA and 40% of patients demonstrate increased level of Abs to dDNA. The
      percent of TBE patients with increased concentration of anti-nDNA Abs higher then
      that in patients with multiple sclerosis (18%) and some other autoimmune diseases
      (6-18%), but comparable with that for patients with systemic lupus erythematosus
      (38%) and polymyositis (42%). In contrast to patients with systemic lupus
      erythematosus and multiple sclerosis, the level of Abs to nDNA in patients with
      TBE is higher than the level of Abs to dDNA. Correlation coefficients of Ab
      levels to both n- and dDNA were estimated for group of patients in whole and for
      separate subgroups with different type of disease (temperature reaction,
      feverishness and meningitis). Analysis of correlation between titres of anti-DNA
      Abs and three standard biochemical markers of TBE (activity of aspartate- and
      alanine-aminotransferases, and concentration of whole bilirubin) for 22 patients
      with TBE was carried out. Statistically significant correlation was revealed only
      between the level of Abs to nDNA and activities of aspartate- and alanine
      aminotransferases, correlation coefficients are equal to +0.44 and +0.48,
      respectively.

PMID- 15456146
TI  - [Neurodevelopmental disorders in children with an antecedent of
      subependymal/intraventricular hemorrhage at 3 years of age].
AB  - Intraventricular and subependymal hemorrhage are common complications among
      preterm infants. The aim of the present study was to assess its implication in
      the neurodevelopment at 3 years of age. MATERIAL AND METHODS: Cerebral
      ultrasonography with evidence of any stage of intraventricular hemorrhage
      (Papille's classification) during neonatal period and a neurologic evaluation at
      3 years of age were performed on each patient. One hundred twenty four patients
      were enrolled and assigned to four groups according the intraventricular
      hemorrhage (IVH) stage: Grade 1, 14 patients, grade II, 84, grade III, 22, and
      grade IV nine patients. RESULTS: Morbility was similar for all groups;
      hydrocephalus was more frequent in group III (73%), and in group IV chronic
      pulmonary disease (77%) was more frequent. Forty five percent of the sample
      showed neurologic alterations with the greatest proportion in group IV (89%); OR
      for groups III and IV was 3.51 with a 95% confidence interval of (1.49, 8.28 p =
      0.005). Grades III&IV showed lowest Terman Merril scores and grade IV scores were
      within the range of mental retardation. No statistical difference was found
      between grades at audition evaluation. CONCLUSIONS: Neurologic alterations were
      greater in poorer grades of IVH, and risk will increment for grades III and IV.
      Associated pathologies for IVH grades III and IV were hydrocephalus and chronic
      pulmonary disease.

PMID- 15456147
TI  - [Monoclonal gammopathy of undetermined significance (MGUS) in Mexican mestizos:
      one institution's experience].
AB  - Monoclonal gammopathy of undetermined significance (MGUS) is defined as presence
      of serum monoclonal protein at a concentration of 3 g per deciliter or less, no
      monoclonal protein or only moderate amounts of monoclonal light chains in urine,
      absence of lytic bone lesions, anemia, hypercalemia, and renal insufficiency
      related with monoclonal protein, and with a proportion of plasma cells in bone
      marrow of 10% or less. In Caucasian population, MGUS affects about 3% of
      individuals > 70 years of age, whereas in Mexican mestizos this figure is
      substantially lower (0.7%); on the other hand, MGUS represents in Mexico only
      2.4% of all monoclonal gammopathies. In a total of 9081 individuals studied
      prospectively at the Centro de Hematologia y Medicina Interna de Puebla
      throughout a 20-year period, 11 patients with MGUS were identified. Median age
      was 70 years (range 43-83 years). Patients have been followed in periods ranging
      from 6 to 3270 days (median, 308 days). Two patients evolved into overt multiple
      myeloma at 308 and 1687 days after diagnosis of MGUS. Overall median survival
      (SV) of the group has not been reached, whereas 3270 days overall SV is 91%.
      After discussing underreporting, biasing, and other confounding factors, it would
      seem that MGUS, like other monoclonal gammopathies, is less frequent in Mexican
      mestizos than in Caucasians. Routine screening studies to identify the condition
      should result in increased numbers of patients.

PMID- 15456148
TI  - [Medical education challenged by the learning society].
AB  - This paper analyzes the limitations of dominant paradigms in education and
      identifies the necessity of research-situated learning in real environments and
      how medical education must be involved with knowledge management in real,
      complex, adaptive systems, and concludes with the need for constructing novel
      educative paradigms with regard to new educational paradigms.

PMID- 15456149
TI  - [Anti-Brucella antibody seroprevalence in blood donors for therapeutic ends at
      three blood banks of the Mexican Institute of Social Security].
AB  - INTRODUCTION: To determine seroprevalence for Brucella sp. in blood donors, a
      serologic study was carried out at three blood banks of the Instituto Mexicano
      del Seguro Social (IMSS). METHODS: 500 blood samples were taken from selected
      blood donors. Laboratory tests were used, such as Bengal rose (BR), Standard
      agglutination in microplate (SAM) and in presence of 2-Mercaptoethanol
      agglutination in microplate (2ME), which were applied to 500 blood sera from
      selected effective blood donors. The sample was representative according to the
      statistical analysis developed. RESULTS: 18 of 500 analyzed sera were positive,
      with seroprevalence of 3.6%, male sex (83.4%), predominating, as secondary
      activity group (72.2%). According to academic archivement, blood donors with
      secondary school had highest seropositivity (55.6%). CONCLUSION: In this study,
      we conclude that brucellosis has peculiar epidemiologic characteristics in blood
      banks that participated in this research; therefore it is highly recommended to
      perform screening tests such as BR, SAM, and 2ME to identified anti-Brucella
      antibodies in the sera of effective blood donors.

PMID- 15456150
TI  - [Clinicopathologic characteristics and distribution of number of autopsies of
      patient death due to coccidioidomycosis at a referral hospital in northeastern
      Mexico].
AB  - AIMS: 1. To describe clinical and pathologic characteristics of patients with
      coccidioidomycosis (CM) who died from 1983-2000 at a hospital in northeastern
      Mexico, and 2, to know distribution of number of deaths due to CM per year and
      month. METHODS: From 4598 autopsies, 31 cases of CM were selected. Clinical chart
      and autopsy protocols were examined. Distribution of cases was analyzed by
      contingence table and Kolmogorov-Smirnov tests. RESULTS: There were 10 women and
      21 men (aged 4 months to 60 years). In women, pregnancy was present in 40% of
      cases. In men, chronic renal failure (CRF) (38%) and AIDS (19%) were the
      pathologic conditions most frequently observed. Variation in distribution of
      cases throughout 18 years was not observed (p > 0.05). CONCLUSIONS: Mortality due
      to CM was 0.67% and variation in number of deaths was not found. In this endemic
      area, CM must be included in differential diagnosis of patients with risk factors
      such as pregnancy, CRF, and AIDS, especially if associated with pneumonia with
      miliary pattern or septicemia with splenomegaly.

PMID- 15456151
TI  - [Surgical treatment for trigeminal neuralgia].
AB  - We treated 50 patients at the Hospital de Especialidades, Centro Medico Nacional
      La Raza, IMSS, in Mexico City, with trigeminal neuralgia by two procedures: a)
      microvascular decompression of the trigeminal nerve with asterional craniectomy,
      or b) compression of Gasser's nodule by percutaneous puncture. Each patient was
      allowed to choose one of the procedures after informed consent. Twenty two
      patients underwent percutaneous puncture, while 28 patients underwent
      microvascular decompression. Our study group comprised 35 females and 15 males
      between the ages of 38 and 80 years. After 3 months, we achieved good-to
      excellent results in 25 patients with microvascular decompression and in 15
      patients, with compression of Gasser's nodule. At 2 years follow-up, our results
      remained the same for microvascular decompression group while in the other group
      we observed only satisfactory results in 59% of cases. In craniectomy group, we
      found vascular compression in 96% of cases. Five patients presented hypoacusia
      after decompressive procedure and eight patients had facial dysesthesia after
      percutaneous procedure. In percutaneous group, procedures were cancelled due to
      technical difficulties in two cases. We conclude that both procedures are safe,
      with zero mortality. The microvascular procedure affords better results at 2
      years follow-up.

PMID- 15456152
TI  - [Antecedents of Mexican medical science as seen through the figure of Dr. Daniel
      Vergara Lope Escobar (1865-1938)].

PMID- 15456153
TI  - [The benefits of doing excercise in the elderly].
AB  - Advanced age is associated with changes in body composition such as muscular mass
      loss, which is defined as sarcopenia. The former term plays a key role in the
      frailty model, although its source is unknown. Myriad strategies have been used
      to improve and increase muscular mass and function in older persons. The muscle
      is a versatile system that owes its great capacity to adaption to regular
      exercise programs. Aerobic exercise and resistance training improve muscular
      function and can minimize and even reverse sarcopenia in the elderly (healthy,
      very elderly or frail). The main difference in prescribing exercise for healthy
      adults and elderly individuals is that intensity of training program is lower for
      the latter. This review is aimed toward the physiopathologic aspects and clinical
      implications regarding muscular mass loss and to programs directed toward
      increasing strength and/or endurance in the elderly.

PMID- 15456154
TI  - [Molecular aspects of chronic hyperglycemia-induced tissue damage].
AB  - The knowledge of the molecular basis of diabetes mellitus physiopathology will
      allow improvements in treatment or prevention of the disease. Diabetes mellitus
      is a complex disease in which hyperglycemia leads to complications in several
      organs. In this condition, there is increase in reactive oxygen species (ROS) as
      a result of glucose autooxidation; its metabolism produces accumulation of
      metabolites such as fructose, sorbitol, and triose phosphate. The latter
      generates a oxoaldehydes with high capacity to produce protein glycation and
      oxidative stress. Moreover, there is an increase in synthesis of diacylglycerol
      from triosephosphate, which activates protein kinase C. On the other hand,
      alteration of normal ratio between reduced and oxidized niacinamide nucleotides
      leads to low efficiency of antioxidative systems. Finally, this metabolic
      dysregulation causes altered signal transduction, abnormal gene expression, and
      tissue damage, resulting in development of diabetic complications.

PMID- 15456155
TI  - [A 32-year-old woman with cephalea, galactorrea, prognatism, and acral growth].

PMID- 15456156
TI  - [Cardiac tamponade in the neonate as a complication of a central venous catheter.
      Case report].
AB  - BACKGROUND: Central venous access is a necessity for the critically-ill newborn
      who arrives at a Neonatal Intensive Care Unit; despite being considered a
      relatively safe procedure, it may cause to complications with fatal consequences.
      OBJECTIVE: To describe the course of five newborn patients undergoing cardiac
      tamponade as a complication of central venous catheter. DESIGN: Case series.
      MATERIAL AND METHODS: Clinical files of five newborn patients admitted to the
      NICU who had had central venous catheter installed and underwent cardiac
      tamponade as a complication were reviewed. Data was collected on a previously
      designed chart in which identification, venous access, time installed before
      complication, diagnosis, treatment, and development were registered. RESULTS:
      Expressions of central tendency and dispersion were used for statistical
      analysis. Four preterm infants and one term infant were analyzed; mean
      gestational age was 31.5 weeks. Lapse between installation of centralvenous
      catheter and appearance of cardiac tamponade was 3 to 12 days, with mean of 6.2
      days. The previously mentioned diagnosis was suspected when patients presented
      sudden hemodynamic dysfunction. Diagnosis was confirmed by echocardiography after
      resuscitation. Pericardic punction was performed in all patients, but only in
      four patients was nutrition admixture was obtained. CONCLUSIONS: We consider
      superior cava vein to be the safest site to place a central venous catheter above
      right atrium. Its position must periodically be confirmed via x-ray because of
      risk of migration phenomenom. Pericardic punction should be considered when a
      patient suddenly requires cardiopulmonary resuscitation and does not respond to
      common reanimation maneuvers.

PMID- 15456157
TI  - [Primary renal angiosarcoma].
AB  - The twenty-fourth case of primary renal angiosarcoma is described, according to
      the available international literature, this present in a 71-year-old male, a
      mechanic by trade, without carcinogenic antecedents. Hematuria, pain in flank,
      and left-side tumoral mass of approximately 20 cm in diameter located in kidney
      by computerized axial tomography (CT) constituted manifestations. A left
      nefrectomy was performed. No metastasis was found. The tumor replaced 4/5 of the
      organ and weighed 1145 g. It showed angiomatous structure with atypical
      proliferation of endothelial cells in a sinusoldal trauma and anastomosatic
      vascular channels that invaded neighboring parenchymal and capsule. Tymorous
      cells were positive for CD31 and CD34 and negative for cytokeratins, S100 and HMB
      45 proteins. The patient was subjected to treatment with chemotherapy and
      radiotherapy (lineal accelerator), but 12 months after surgery he presented
      retroperitonal tumoral relapse and hepatic metastasis. Diagnostic differentiation
      with benign vascular tumors is pointed out, as well as carcinomas and sarcomas
      that showed an outstanding angiomatous component, both primary and/or secondary.
      Primary renal angiosarcoma exposes the multiplicity of localizations that it is
      capable of with a tumor of this type, as well as renal parenquimatous capacity to
      be the seat of a great variety of neoplasias.

PMID- 15456158
TI  - [Causality in medicine].
AB  - The concept of causality is a part of every day life because man has always
      searched for the why of things as a way of dealing with and adapting to the
      world. In medicine, one of the central aims of study is identification of the
      factors or agents that cause disease with the intention of establishing
      treatments and especially, to apply preventive strategies. In this work, we
      conducted a brief review of the philosophical positions on causality, its
      biological models, as well as the tools used in clinical epidemiology to evaluate
      causal associations.

PMID- 15456159
TI  - [Occult pneumothorax].

PMID- 15456160
TI  - [Genes and Parkinson's disease].

PMID- 15456161
TI  - [Anniversary of the death of Dr Manuel Velasco Suarez: paradigm of a human being
      (1914-2001)].

PMID- 15456162
TI  - First record of Contracaecum spp. (Nematoda: Anisakidae) in fish-eating birds
      from Zimbabwe.
AB  - Endoparasites of fish-eating birds, Phalacrocorax africanus, P. carbo, Anhinga
      melanogaster and Ardea cinerea collected from Lake Chivero near Harare, Zimbabwe,
      were investigated. Adult Contracaecum spp. were found in the gastrointestinal
      tract (prevalence 100 % in P. africanus, P. carbo and A. melanogaster; 25 % in A.
      cinerea). Parasite intensity was 11-24 (mean 19) in P. africanus, 4-10 (mean 7)
      in P. carbo, 4-56 (mean 30) in A. melanogaster and 2 (mean 0.5) in A. cinerea.
      The cormorants fed mainly on cichlid fishes and carp; the darters and the grey
      herons on cichlids. All these fishes are intermediate hosts of Contracaecum spp.
      Scanning electron microscopy revealed that Contracaecum rudolphii infected both
      cormorant species and darters; C. carlislei infected only the cormorants while C.
      tricuspis and C. microcephalum infected only the darters. Parasites from the grey
      heron were not identified to species because they were still developing larvae.
      These parasites are recorded in Zimbabwe for the first time.

PMID- 15456163
TI  - Severe hypoxaemia in field-anaesthetised white rhinoceros (Ceratotherium simum)
      and effects of using tracheal insufflation of oxygen.
AB  - White rhinoceros anaesthetised with etorphine and azaperone combination develop
      adverse physiological changes including hypoxia, hypercapnia, acidosis,
      tachycardia and hypertension. These changes are more marked in field
      anaesthetised rhinoceros. This study was designed to develop a technique to
      improve safety for field-anaesthetised white rhinoceros by tracheal intubation
      and oxygen insufflation. Twenty-five free-ranging white rhinoceros were
      anaesthetised with an etorphine and azaperone combination for translocation or
      placing microchips in their horns. Once anaesthetised the rhinoceros were
      monitored prior to crating for transportation or during microchip placement.
      Physiological measurements included heart and respiratory rate, blood pressure
      and arterial blood gas samples. Eighteen rhinoceros were intubated using an
      equine nasogastric tube passed nasally into the trachea and monitored before and
      after tracheal insufflation with oxygen. Seven rhinoceros were not intubated or
      insufflated with oxygen and served as controls. All anaesthetised rhinoceros were
      initially hypoxaemic (percentage arterial haemoglobin oxygen saturation (%O2Sa) =
      49% +/- 16 (mean +/- SD) and PaO2 = 4.666 +/- 1.200 kPa (35 +/- 9 mm Hg)),
      hypercapnic (PaCO2 = 8.265 +/- 1.600 kPa (62 +/- 12 mm Hg)) and acidaemic (pHa =
      7.171 +/- 0.073 ). Base excess was -6.7 +/- 3.9 mmol/l, indicating a mild to
      moderate metabolic acidosis. The rhinoceros were also hypertensive (systolic
      blood pressure = 21.861 +/- 5.465 kPa (164 +/- 41 mm Hg)) and tachycardic (HR =
      107 +/- 31/min). Following nasal tracheal intubation and insufflation, the %O2Sa
      and PaO2 increased while blood pHa and PaCO2 remained unchanged. Tracheal
      intubation via the nose is not difficult, and when oxygen is insufflated, the
      PaO2 and the %O2Sa increases, markedly improving the safety of anaesthesia, but
      this technique does not correct the hypercapnoea or acidosis. After regaining
      their feet following reversal of the anaesthesia, the animals' blood gas values
      return towards normality.

PMID- 15456164
TI  - A retrospective case series of computer-controlled total intravenous anaesthesia
      in dogs presented for neurosurgery.
AB  - This article describes the anaesthetic management and use of total intravenous
      anaesthesia (TIVA) for neurosurgery in 4 dogs. Propofol in conjunction with
      morphine was used for the maintenance of anaesthesia. Anaesthesia was induced
      with either thiopentone or propofol. The program Stelpump (a target-controlled
      infusion program) was run on a laptop and connected to a syringe driver via an RS
      232 cable. The program was found to be reliable and safe for the administration
      of TIVA in dogs. Invasive monitoring was required in order to monitor
      cardiovascular changes during surgery. Ventilation was controlled to maintain the
      end-tidal carbon dioxide below 40 mm Hg. The anaesthesia was characterised by
      haemodynamic stability. The haemodynamic stability was probably the result of the
      choice of TIVA and balanced anaesthesia. Intracranial pressure and oedema was
      controlled with dexamethasone, mannitol and ventilatory management either in
      combination or alone. Three dogs survived to hospital discharge and 1 dog was
      euthanased 2 weeks later due to tumour metastasis. The development and
      characterisation of the anaesthetic effects of TIVA needs to be elucidated in
      order to provide clinicians with rational guidelines for the appropriate use of
      TIVA in veterinary medicine.

PMID- 15456165
TI  - Detection of bovine viral diarrhoea virus in specimens from cattle in South
      Africa and possible association with clinical disease.
AB  - Studies covering all aspects of bovine viral diarrhoea virus (BVDV) have been
      conducted in several countries in Europe, Asia and America. In southern Africa,
      more information is required about the nature of BVDV infection, the prevalence
      of different strains and the economic importance of the disease. The presence of
      BVDV in southern Africa has been known since the early 1970s through serological
      surveys but few reports confirming its presence by virus isolation and
      correlation with clinical disease are available. Specimens (n = 312) collected in
      1998/99, from live and dead cattle from different farming systems, were obtained
      from private practitioners, feedlot consultants and abattoirs throughout the
      country. Specimens (n = 37) from African buffaloes (Syncerus caffer) in the
      Kruger National Park were also included. All specimens were processed for virus
      isolation in cell culture with confirmation by means of immunofluorescent
      antibody tests and some also by means of an antigen capture ELISA. BVDV was
      isolated from 15 (4.7%) cattle and were all noncytopathic biotypes. BVDV was not
      detected in 37 lymph nodes obtained from buffaloes in the Kruger National Park.
      Of the clinical signs in cattle from which virus were isolated, respiratory signs
      was the most frequent (10/15), followed by diarrhoea (5/15). Abortion, congenital
      malformations, haemorrhagic diarrhoea and poor growth were also included as
      criteria for selection of animals for specimen collection, but no BVD viruses
      were isolated from cattle manifesting these clinical signs.

PMID- 15456166
TI  - Diagnosis of feline haemoplasma infection using a real-time PCR assay.
AB  - Haemobartonella felis has been reclassified within the genus Mycoplasma as
      Mycoplasma haemofelis and 'Candidatus Mycoplasma haemominutum', collectively
      referred to as the feline haemoplasmas. A total of 78 cats from the Johannesburg
      area that had blood samples submitted to a private veterinary laboratory were
      tested using a real-time polymerase chain reaction (PCR) assay able to detect and
      distinguish the two feline haemoplasma (basonym Haemobartonella) species. All
      samples had been diagnosed with haemoplasma infection by cytological examination
      of blood smears. Statistical analysis was performed to evaluate associations
      between haemoplasma status, age, and haematological and biochemical parameters.
      On PCR assay 43 cats (55%) were haemoplasma negative, 25 (32.1%) positive for
      'Candidatus Mycoplasma haemominutum', 5 (6.4%) positive for Mycoplasma haemofelis
      and 5 (6.4%) positive for both species. Significant inverse correlation was found
      between the amount of M. haemofelis DNA present in the blood and the haematocrit
      value. Cats that were positive for M. haemofelis showed macrocytic regenerative
      anaemia, monocytosis and thrombocytopaenia. This report documents the existence
      of both haemoplasma species in cats in South Africa.

PMID- 15456167
TI  - The use of the standard exercise test to establish the clinical significance of
      mild echocardiographic changes in a Thoroughbred poor performer.
AB  - A 4-year-old Thoroughbred gelding racehorse was referred to the Onderstepoort
      Veterinary Academic Hospital (OVAH) with a history of post-race distress and
      collapse. In the absence of any obvious abnormalities in the preceding diagnostic
      work-up, a standard exercise test was performed to determine an underlying cause
      for the post-race distress reported. In this particular case oxygen desaturation
      became evident at speeds as slow as 6 m/s, where PO2 was measured at 82.3 mm Hg.
      Similarly at a blood pH of 7.28, PCO2 had dropped to 30.0 mm Hg indicating a
      combined metabolic acidosis and respiratory alkalosis. The cause of the distress
      was attributed to a severe hypoxia, with an associated hypocapnoea, confirmed on
      blood gas analyses, where PO2 levels obtained were as low as 56.6 mm Hg with a
      mean PCO2 level of 25.4 mm Hg during strenuous exercise. Arterial oxygenation
      returned to normal immediately after cessation of exercise to 106.44 mm Hg, while
      the hypocapnoeic alkalosis, PCO2 25.67 mm Hg, persisted until the animal's
      breathing normalized. The results obtained were indicative of a dynamic cardiac
      insufficiency present during exercise. The combination of an aortic stenosis and
      a mitral valve insufficiency may have resulted in a condition similar to that
      described as high-altitude pulmonary oedema, with respiratory changes and
      compensation as for acute altitude disease. The results obtained were indicative
      of a dynamic cardiac insufficiency present during exercise and substantiate the
      fact that an extensive diagnostic regime may be required to establish a cause for
      poor performance and that the standard exercise test remains an integral part of
      this work-up.

PMID- 15456168
TI  - Suppurative rhinitis associated with Haemophilus species infection in a cat.
AB  - A young cat with signs of chronic rhinitis was evaluated for underlying
      anatomical, inflammatory, or infectious disease. Initial diagnostics were
      significant for the isolation of an unusual pathogen, Haemophilus species.
      Isolation using a human RapID NH system erroneously identified the isolate as H.
      segnis, a human pathogen. No database of veterinary pathogens (Haemophilus) are
      included in the system and animal pathogens will either be erroneously identified
      or yield a unique biocode not listed. Because of the unique nature of the
      pathogen we explored the possibility of immunosuppression as a contributory
      factor to infection. A variety of laboratory tests were employed to evaluate
      immune function. The clinical indications and utility of immune function testing
      are discussed. No immune dysfunction was identified.

PMID- 15456169
TI  - Coexistence of Hodgkin's disease and Castleman's disease.

PMID- 15456170
TI  - Rectal plasmacytoma.

PMID- 15456171
TI  - Unifocal intranodal Langerhans' cell histiocytosis associated with metastatic
      breast carcinoma.

PMID- 15456172
TI  - Interinstitutional comparison of frozen section consultation in small hospitals:
      a College of American Pathologists Q-Probes study of 18,532 frozen section
      consultation diagnoses in 233 small hospitals.
AB  - OBJECTIVE: To study pathology intraoperative consultation practices and the
      accuracy of diagnoses made by frozen section. DESIGN: In 1994, participants in
      the College of American Pathologists Q-Probes laboratory quality improvement
      program each completed questionnaires and prospectively collected data on up to
      20 frozen section procedures performed over a 5-month period. SETTING: Surgical
      pathology laboratories serving private and public hospitals with 300 or fewer
      occupied beds. PARTICIPANTS: Two hundred thirty-two North American institutions
      and one New Zealand institution. MAIN OUTCOME MEASURES: The discordance and
      deferral rates of frozen section diagnoses and the reasons for frozen section
      discordance relative to corresponding diagnoses made on permanent (paraffin)
      sections. Calculation of frozen section discordance rates excluded diagnoses of
      subtypes or grade of malignancy, biopsies on specimens in which there was no
      gross lesion (eg, mammographic specimens), thyroid follicular lesions, tissue
      taken only to determine adequacy for other studies (eg, estrogen-binding
      proteins), and frozen sections performed to evaluate margins of specimens
      oriented en face. RESULTS: Out of 18,532 frozen section diagnoses performed on
      327,884 surgical cases, 859 (4.6%) diagnoses were deferred until permanent
      sections were available for review; 17,357 (98.2%) nondeferred diagnoses agreed
      with, and 316 (1.8%) disagreed with, those diagnoses rendered on permanent
      sections. The most common cause of discordance was underdiagnosis of neoplasia,
      usually due to block- or tissue-sampling errors. CONCLUSIONS: We recommend that
      laboratories routinely monitor frozen section discordance, cut additional
      sections deeper into the frozen block and/or sample additional tissue when the
      initial frozen section diagnosis is negative or nonproductive, reconcile all
      discordant frozen section diagnoses in the final report, and periodically assess
      the value of performing frozen section examinations.

PMID- 15456173
TI  - Reasons for proficiency testing failures in clinical chemistry and blood gas
      analysis: a College of American Pathologists Q-Probes study in 665 laboratories.
AB  - OBJECTIVE: To determine the reasons for proficiency testing (PT) failures from 41
      chemistry and blood gas analytes using data collected to benchmark performance.
      DESIGN: Self-administered survey requesting number of challenges by analyte
      encompassing nine PT events. When the challenge resulted in a self-defined
      failure, further information was requested concerning the magnitude of the
      failure (as a standard deviation index) and categorization of the type of failure
      into six major groups (Methodologic, Technical, Clerical, Survey, Unexplained, or
      Other) and then into subgroups. PARTICIPANTS: Laboratories enrolled in the 1992
      College of American Pathologists Q-Probes program. MAIN OUTCOME MEASURES: Rate of
      PT failures and reasons for failure. RESULTS: Proficiency testing data from
      670,489 challenges performed in 665 laboratories revealed 9268 (1.4%)
      unacceptable results. Failure types were distributed as follows: Methodologic,
      33.5%; Technical, 17.4%; Clerical, 11.1%; Survey, 7.8%; Unexplained, 25.7%; and
      Other, 7.4%. CONCLUSIONS: Individual analyte PT failure is a common event in the
      participating laboratories, but failures in successive or alternate events are
      rare. Analysis of the reasons for failed events indicates that most identified
      reasons occurred in either the Methodologic or Technical categories (50.9%).
      Analysis of the failure types suggested investigation pathways based on the
      magnitude of the failure that could reduce the 25.7% rate of unexplained
      failures.

PMID- 15456174
TI  - Practice protocol for the examination of specimens removed from patients with
      carcinoma of the urinary bladder, ureter, renal pelvis, and urethra.
AB  - This article details a practice protocol for the examination and reporting of
      specimens removed from patients with carcinoma of the urinary bladder, ureter,
      renal pelvis, or urethra. It was created by a multidisciplinary task force of
      pathologists and oncologists established by the Cancer Committee of the College
      of American Pathologists. Documentation for the protocol was obtained from the
      previously published protocol, the medical literature, personal experience, and
      consultation with colleagues. After creation and review by the task force, the
      protocol was sent to 1000 randomly selected practicing pathologists as a survey.
      Their comments and suggestions were addressed in the final version. The protocol
      was approved by the Board of Governors of the College of American Pathologists.

PMID- 15456175
TI  - Small intraductal papillary-mucinous adenomas of the pancreas.
AB  - Intraductal papillary-mucinous tumors in the pancreas have recently been
      described as a distinct entity, but the classification of these neoplasms remains
      under debate. Of issue is the biologic potential of these lesions and the
      predictability of clinical behavior on the basis of histologic appearance. We
      report two cases with intraductal papillary tumors formed by highly
      differentiated mucin-containing columnar epithelium found incidentally at
      autopsy. Both were classified as adenomas on the basis of histologic features.
      Neither patient experienced symptoms from their lesion during life and both died
      of other causes. Both lesions were studied by the polymerase chain reaction and
      were found to harbor codon 12 mutations in the c-K-ras gene. The concept that
      these neoplasms represent an early stage in an adenoma-carcinoma sequence is
      discussed.

PMID- 15456176
TI  - Touch imprints in the intraoperative diagnosis of anterior mediastinal neoplasms.
AB  - OBJECTIVE: To evaluate the accuracy of intraoperative diagnosis of mediastinal
      lesions using touch imprints and frozen sections. DESIGN: We studied touch
      imprints and frozen sections from 21 anterior mediastinal lesions
      retrospectively. The lesions included six cases of non-Hodgkin's lymphoma, eight
      thymomas, two thymic carcinomas, three Hodgkin's disease cases, and two
      seminomas. Slides were reviewed independently by each of the three authors, and
      diagnoses were recorded. RESULTS: Depending on the observer, the correct
      diagnosis was obtained on touch imprints alone in 76% to 81% of cases. On frozen
      sections alone, the correct diagnosis was made in 67% to 86% of cases. In 86% to
      100% of cases, the correct diagnosis was made on either touch imprint or frozen
      section. CONCLUSIONS: As with frozen sections, the most common significant error
      in interpreting cytology preparations was in distinguishing thymic epithelial
      tumors (thymoma and thymic carcinoma) from lymphoma. On a modified Wright-Giemsa
      stained imprint, epithelial cells in a thymoma may be inconspicuous. Clues to
      their presence include cells with a spindled nuclear shape or a small distinct
      nucleolus. The epithelial cells have scant cytoplasm with indistinct cell
      borders. Clumping of cells is often not prominent in lymphocytic thymomas, but
      may be present in epithelial or mixed lymphocytic and epithelial tumors. With
      practice, one can learn to recognize thymic epithelial cells on touch imprints.
      Familiarity with this simple inexpensive technique could improve the accuracy of
      intraoperative diagnosis of anterior mediastinal lesions.

PMID- 15456177
TI  - Botryomycosis ('bacterial ball') of the sinonasal tract caused by Pseudomonas
      aeruginosa.
AB  - BACKGROUND: Botryomycosis is a chronic bacterial infection that typically
      presents as a cutaneous lesion. Visceral involvement may occur, but mucosal
      disease is uncommon. We report two cases of sinonasal tract botryomycosis that
      clinically simulated a neoplasm. METHODS: Two cases of sinonasal tract
      botryomycosis were identified from the Otolaryngic Tumor Registry at the Armed
      Forces Institute of Pathology, Washington, DC. The clinical records, slides, and
      paraffin blocks were available for both cases. Histochemical stains, including
      Brown and Hopps, Gomori's methenamine-silver, acid-fast bacilli, mucicarmine,
      periodic acid-Schiff, and Warthin-Starry, were performed. RESULTS: The patients
      were an 81-year-old man and a 43-year-old woman. The man presented with acute
      ethmoiditis and a bulging eye. Radiographic studies showed a soft tissue mass in
      his left maxillary antrum with osseous erosion of adjacent anatomic sites. The
      woman presented with persistent headaches of more than 1 year's duration, with
      increasing severity in the months prior to presentation. An expansile soft tissue
      mass was identified in her right maxillary and ethmoid sinuses. Surgery was
      performed on both patients. The histology included amorphous, acellular material
      and separate, rounded eosinophilic granules associated with a neutrophilic
      infiltrate. A Splendore-Hoeppli phenomenon was seen. Filamentous gram-negative
      bacilli, identifiable only by histochemical staining, were morphologically
      compatible with Pseudomonas aeruginosa. Cultures of samples taken from both
      patients intraoperatively confirmed the organisms as P. aeruginosa. CONCLUSIONS:
      Sinonasal botryomycosis is a rare localized disease that may be mistaken
      clinically for an aggressive neoplasm. Complete surgical evacuation is curative.

PMID- 15456178
TI  - Oral condyloma acuminatum associated with human papillomavirus and p53
      overexpression mimicking cyclosporine effect in a transplant patient.
AB  - A case of human papillomavirus-associated condyloma acuminatum in the oral
      cavity, presumed to be fulminant cyclosporine-induced gingival hyperplasia, is
      reported in a 55-year-old cardiac transplant patient. Approximately 47 months
      following the transplant, the patient developed severe hyperplasia of the uvula
      and oral mucosa, resulting in difficulty swallowing. The histopathologic features
      of the lesion were typical of those of condyloma acuminatum. In situ
      hybridization of the paraffin-embedded material revealed infection with human
      papillomavirus types 6/11. This case lends further support to the putative role
      of long-term cellular immunosuppression in the development of human
      papillomavirus-associated squamous lesions. In addition, positive staining for
      p53 protein raises the possibility of concomitant p53 involvement in the
      pathogenesis of this oral lesion.

PMID- 15456179
TI  - Crystal-storing histiocytosis associated with a lymphoplasmacytic neoplasm
      mimicking adult rhabdomyoma: a case report and review of the literature.
AB  - Massive accumulation of crystals within histiocytes in association with a
      lymphoplasmacytic neoplasm causing histologic features closely mimicking adult
      rhabdomyoma is a rare occurrence. We report the case of a 49-year-old man who
      presented with a left posterior cervical mass. Histologic examination
      demonstrated sheets of large, elongated, and polygonal cells with prominent
      eosinophilic cytoplasm surrounding scattered dense lymphoplasmacytic collections.
      Evidence of the reactive histiocytic nature of the eosinophilic cells was
      provided by an immunohistochemical reaction that was positive with KP-1 (CD68),
      but negative with common muscle actin, desmin, and myoglobin. The ultrastructural
      finding of elongated and rhomboid, membrane-bound, cytoplasmic crystals further
      supported the reactive histiocytic nature of these cells. B-cell kappa
      monoclonality of the lymphoplasmacytic component was proven by gene rearrangement
      studies. A recurrence involving the right parotid gland, 18 months after removal
      of the cervical mass, confirmed the aggressive nature of this B-cell lymphoma.
      Misdiagnosis of crystal-storing histiocytosis as adult rhabdomyoma can be avoided
      if the following features are recognized: lack of cytoplasmic cross striations,
      frequent multinucleation of the histiocytes, and prominence of the atypical
      lymphoplasmacytic component.

PMID- 15456180
TI  - Multicentric metachronous pulmonary and intravagal paraganglioma: a case report
      with immunohistochemical findings.
AB  - An unprecedented presentation of multicentric paraganglioma in a 48-year-old man
      is described. One of the paragangliomas, originally diagnosed as a carcinoid
      tumor, presented as a lung mass and was removed. Four years later, an intravagal
      paraganglioma was discovered. The lung and intravagal tumors had identical
      morphologic and immunoreactive characteristics. Both tumors consisted of chief
      cells (type 1) and sustentacular cells (type 2). The chief cells were
      immunoreactive with neuroendocrine markers (synaptophysin and chromogranin), but
      nonreactive with epithelial markers (CAM 5.2, high- and low-molecular-weight
      keratins, epithelial membrane antigen, and carcinoembryonic antigen). The
      sustentacular cells were positive for S100 protein. Although pulmonary carcinoids
      may mimic paragangliomas and occasionally contain sustentacular cells, the
      diagnosis was rejected because the tumor cells did not demonstrate reactivity
      with epithelial markers.

PMID- 15456181
TI  - Gastroesophageal-vulvar leiomyomatosis presenting over the course of 20 years.
AB  - Gastroesophageal-vulvar leiomyomatosis represents a rare syndrome of diffuse
      smooth muscle proliferation primarily in the gastroesophagus and vulva. To our
      knowledge, there are 19 cases reported in the literature, most associated with
      Alport's syndrome. We recently encountered a case not associated with Alport's
      syndrome, which had progressed over the course of 20 years. We used
      immunohistochemistry to further delineate the process. Leiomyomatosis appears to
      be a systemic disorder, with indolent proliferations of smooth muscle in areas
      that may not be clinically significant.

PMID- 15456182
TI  - Malignant schwannoma of the liver in a patient without neurofibromatosis: a case
      report and review of the literature.
AB  - Primary schwannomas of the liver are extremely rare. We report a case of
      malignant schwannoma of the liver occurring in a 49-year-old man, who did not
      have neurofibromatosis, and review the literature. The clinical and histologic
      findings of benign and malignant schwannomas of the liver are compared.

PMID- 15456183
TI  - Biology of aging.

PMID- 15456184
TI  - The College of American Pathologists, 1946-1996. The beginning.

PMID- 15456185
TI  - Persistent organic chlorines as a threat to mother and child health.

PMID- 15456186
TI  - Clinical and morphological features of paediatric myelodysplastic syndromes: a
      review of 34 cases.
AB  - BACKGROUND: The clinical and morphological spectrum of myelodysplastic syndromes
      (MDS) during childhood has not yet been completely documented. We herein present
      the clinical features and morphological data from peripheral blood (PB), bone
      marrow aspirates (BMA) and bone marrow biopsies (BMB) of a series of paediatric
      MDS patients, with particular emphasis on their specific morphological
      characteristics and their diverse underlying genetic background. PATIENTS AND
      METHODS: Thirty-four patients with MDS (median age 8.45 y) were consecutively
      diagnosed and treated during a period of 15 y (1988-2002). Diagnosis was based on
      clinical manifestations, morphology of PB, BMA and BMB, and cytogenetic analysis
      of BM cells. Clonogenic methylcellulose cell cultures were performed in 23/34
      patients. Patients were categorized into group A [26 primary/de novo MDS, i.e.
      refractory anaemia (RA) 18, RA with excess of blasts (RAEB) 2, RAEB in
      transformation (RAEB-t) 6] and group B (8 secondary MDS, i.e. RA 4, RAEB 1, RAEB
      t 3). Treatment options varied according to protocols active during the period of
      the study and the availability of a suitable BM donor. Survival probabilities
      were estimated using the Kaplan-Meier method. RESULTS: Dysplastic features of the
      erythroid, myeloid and megakaryocytic lineage were detected at BMA in 85%, 50%
      and 90% of the patients, respectively, while decreased cellularity was found at
      BMB in 21/34 patients (60%). RA patients of group A presented at BMB significant
      hypocellularity (14/18) as a prominent finding due to decrease of the myeloid
      (13/18 patients) and/or the megakaryocytic (14/18 patients) lineage.
      Hypocellularity in RA was accompanied by dysplasia of the erythroid (17/18
      patients) and megakaryocytic (16/18 patients) lineage, the presence of abnormal
      localization of immature precursors (ALIP, 8/18 patients), fibrosis (5/18) and
      stromal changes (11/18). Chromosomal aberrations were revealed in 17/34 patients,
      of which monosomy 7 was present in seven. Cell cultures demonstrated abnormal
      myeloid and/or erythroid in vitro clonal growth pattern in all the examined
      patients. An associated disorder or inherited disease, was identified in 14/26
      patients (54%) with primary MDS. Cumulative survival of group A patients was
      44.2% (RA 66.6%, RAEB/RAEBt 14.6%; p = 0.001), and of the whole group 42.4%, at
      14 y. CONCLUSIONS: Hypocellularity of significant degree is a constant and
      prominent feature among paediatric MDS, especially those with RA. A large variety
      of associated disorders underlies the clinical appearance of paediatric MDS,
      reflecting their marked heterogeneity. RA represents the prominent subtype during
      childhood (69% in this study), and it appears to have the best prognosis, while
      prognosis of RAEB/RAEBt remains extremely poor.

PMID- 15456187
TI  - Is iron deficiency in infants and young children common in Scandinavia and is
      there a need for enforced primary prevention?
AB  - A significant problem in diagnosing infants and young children with iron
      deficiency (ID) and iron deficiency anemia (IDA) is that it is not clear how the
      biochemical markers used correspond to physiological outcomes such as growth,
      neurodevelopment and morbidity. Thus, the prevalence of iron deficiency and iron
      deficiency anemia in infants and young children is difficult to assess and
      therefore not really known. Recent studies have shown that iron metabolism is
      subjected to developmental changes during infancy, which affect indicators of
      iron status. Hence, better defined cut-off values for the indicators used are
      needed and, in particular, how they are correlated to functional outcomes.

PMID- 15456188
TI  - Wholehearted life support of babies born at 23 weeks of gestation.
AB  - Justification of life support by all means to babies born at 23 wk of gestation.
      Depends upon the needs and wants of the family.

PMID- 15456189
TI  - Parenteral lipids and the preterm infant: between Scylla and Charybdis.
AB  - Intravenous lipid infusions are a valid option for a dense source of energy and
      essential fatty acids when the enteral route is unavailable. However, the use of
      these preparations in neonatal patients has been associated with metabolic
      concerns such as oxidative stress, and complications such as abnormal vascular
      tone, intravascular fat deposition and even fat embolism. Metabolic issues
      related to nutrient accretion and noxious biological reactions should be
      considered when prescribing parenteral lipids with high PUFA content to the
      critically ill newborn infant.

PMID- 15456190
TI  - Ghanaian infant growth study.
AB  - The future revised WHO growth references for infancy and early childhood will
      have an international basis rather than just an American one, as is the case with
      the current NCHS/WHO ones. The anthropometric data for analysis will be collected
      from babies breastfed in accordance with WHO guidelines. An important
      stipulation, however, is that their growth must have been unrestricted by
      environmental factors. A paper from Ghana describes a quantitative provisional
      study that has revealed how such a condition can be satisfied within a developing
      country. Family income and especially the higher education of the father up to
      university level can still be important variables in the achievement of optimal
      growth of babies, even those brought up in situations of relative affluence.

PMID- 15456191
TI  - Effect of BCG vaccine on tuberculin skin tests in 7-11-year-old children.
AB  - AIM: To determine the effect of Bacillus Calmette Guerin (BCG) vaccination on
      tuberculin skin test responses in 7-11-year-old children, and also to clarify
      whether the number of vaccinations and the time interval between vaccination and
      tuberculin skin test have an effect on the test responses. METHOD: 1200 primary
      school children were evaluated for the presence and number of BCG scars. They
      were then given 5 TU PPD-S intra-dermally. Seventy-two hours after the
      application of tests, PPD indurations were measured. RESULTS: Mean indurations
      were 3.7 +/- 3.9, 6.5 +/- 5.4 and 9.2 +/- 7.1 mm in children with no scar, one
      scar and two scars, respectively. No statistical difference was found between
      mean induration of children with one scar and those with two scars. CONCLUSION:
      The effect of the number of BCG vaccinations and the time interval between
      vaccination and tuberculin skin test application on tuberculin skin test
      responses was statistically insignificant.

PMID- 15456192
TI  - Influence of anthropometric parameters on the body composition measured by
      bioelectrical impedance analysis or DXA in children.
AB  - AIM: To investigate the influence of anthropometric measures (skinfold
      thicknesses, girths, lengths and breadths/lengths) on (1) the whole body
      impedance and impedance index and (2) the body fat mass measured by means of DXA
      in children. METHODS: Nine skinfolds, 13 girths, eight lengths and eight
      breadths/lengths were measured in 26 boys and 27 girls, 11-12 y of age. The
      somatotype components-endomorphy, mesomorphy and ectomorphy--were assessed
      according to the method of Carter and Heath. Body impedance at 50 kHz was
      measured (Multiscan 5000, Bodystat Ltd, UK) and impedance index (height2 /
      impedance) was calculated. Four body components-total body fat mass and separate
      hands, legs and trunk fat mass--were determined using DXA. RESULTS: Skinfold
      thicknesses did not influence body impedance or impedance index according to
      stepwise multiple regression analysis. Impedance index was influenced more by the
      girth measures than was body impedance. The leg length measures highly influenced
      the impedance index (50-81%, R2 x 100). Different breadth/length parameters
      influenced body impedance and body impedance index (21-49%). Mesomorphy
      influenced body impedance only in boys (35%). Body fat mass measured by DXA was
      highly dependent on the measured skinfold thicknesses (59-92%). The influence of
      lengths and breadths/lengths on the total fat mass was significant (25-49%).
      Endomorphy characterized total fat mass as 86% and 52% in boys and girls,
      respectively. CONCLUSION: Variation in anthropometry highly determined the
      variance observed in impedance in children, and the girths were the best
      predictors of impedance. Selected skinfold thicknesses highly predicted fat mass
      measured by DXA for total body, trunk, arms and legs.

PMID- 15456193
TI  - Faecal elastase-1 test is superior to faecal lipase test in the assessment of
      exocrine pancreatic function in cystic fibrosis.
AB  - BACKGROUND AND AIMS: Direct tests are characterized by the highest sensitivity
      and specificity. However, their practical use, especially in children, is
      limited. Among the indirect tests, the highest sensitivity and specificity was
      documented for faecal elastase-1 test, yet the value of faecal lipase test in
      cystic fibrosis (CF) has not been defined. Therefore, the aim of the present
      study was to compare the sensitivity and the specificity of the faecal lipase
      test to the faecal elastase-1 test in the assessment of exocrine pancreatic
      function in children with CF. METHODS: The study comprised 90 CF patients and 95
      healthy subjects (HS). In all subjects, faecal elastase-1 concentrations (ELISA)
      and lipase activities (ELISA) were measured. The presence of pancreatic
      insufficiency was documented by the determination of faecal fat excretion in 78
      pancreatic insufficient and by the secretin-cholecystokinin test in 12 CF
      patients without steatorrhoea. Sensitivity and specificity of the faecal elastase
      1 test and faecal lipase test were analysed and, in 50 HS, sample-to-sample and
      day-to-day variations were determined. RESULTS: With cut-off levels providing the
      same specificity for both tests (95.8%), the sensitivity of the faecal elastase-1
      test (91.1%) was significantly higher (p < 0.0036) than that of the faecal lipase
      test (76.7%). Sample-to-sample (mean +/- SEM: 13.2 +/- 1.2% vs 23.4 +/- 2.2%) and
      day-to-day variations (mean +/- SEM: 16.3 +/- 1.2% vs 32.5 +/- 2.6%) were
      significantly lower (p < 0.0001) for elastase-1 than for lipase measurements.
      CONCLUSION: Among indirect tests, faecal elastase-1 test is superior to faecal
      lipase test in the assessment of exocrine pancreatic function in cystic fibrosis.

PMID- 15456194
TI  - Using radioligand-binding assays to measure tissue transglutaminase
      autoantibodies in young children.
AB  - AIM: To measure autoantibodies against tissue transglutaminase (tTG) in young
      children prospectively screened for coeliac disease (CD). METHODS: In total, 652
      children aged 2.9 (2.5-4.2) y were analysed for IgA-tTG and IgG-tTG with
      radioligand-binding assays and IgA endomysial antibodies (EMA) by indirect
      immunofluorescence. Antibody-positive children were retested after 1.2 (range 0.2
      1.9) y. Intestinal biopsy was performed on children with persistently high
      antibody levels. RESULTS: In total, 3.2% (95% CI: 1.9-4.6%) of the 652 children
      were positive for at least one antibody at baseline: 2.5% (95% CI: 1.3-3.7%) for
      IgA-tTG, 1.7% (95% CI: 0.7-2.7%) for IgG-tTG and 2.9% (95% CI: 1.6-4.2%) for IgA
      EMA, respectively. Ten children were positive for all three antibodies, five for
      both IgA-tTG and EMA, four for EMA only, one for IgA-tTG and another for IgG-tTG.
      IgA-EMA titres correlated with IgA-tTG levels (r = 0.73, p = 0.0003). At follow
      up, seven of 20 children remained positive for all three antibodies, three for
      IgA-tTG only, one for both IgA-tTG and EMA, one for IgA-tTG and IgG-tTG, and the
      remaining child refused further participation. Three biopsies showed villous
      atrophy, two increased intraepithelial lymphocytes and two normal findings.
      Biopsy was not performed in four children with low or declining tTG antibody
      levels at follow-up and in one child who declined. CD was evident in 0.5% (95%
      CI: 0.0-1.0%) (3/652). CONCLUSION: This study revealed a high number of young
      children positive for tTG antibodies as well as EMA, but the majority showed
      declining levels in both antibodies over time. We suggest using radioligand
      binding assays for quantitative measurement of tTG antibodies when change in
      antibody levels is studied in young children.

PMID- 15456195
TI  - Relation of serum leptin and insulin-like growth factor-1 levels to intima-media
      thickness and functions of common carotid artery in children and adolescents with
      type 1 diabetes.
AB  - BACKGROUND AND AIM: Leptin and insulin-like growth factor-1 (IGF-1) have been
      suggested to be involved in the pathogenesis of atherosclerosis. The aim of this
      study was to evaluate the relationship between serum leptin, IGF-1 and intima
      media thickness (IMT) and functions of common carotid artery (CCA) in children
      and adolescent patients with type 1 diabetes. MATERIAL AND METHODS: Serum leptin
      and IGF-1 levels were measured in 45 diabetic patients (23 girls and 22 boys).
      Age, diabetes duration as well as major cardiovascular risk factors, including
      anthropometric and metabolic parameters, were matched between girls and boys. The
      relation of serum leptin and IGF-1 levels to CCA structure and functions were
      measured by ultrasonography as IMT, cross-sectional compliance (CSC), cross
      sectional distensibility (CSD), diastolic wall stress (DWS) and incremental
      elastic modulus (IEM). RESULTS: Serum leptin levels of diabetic girls were higher
      than those in the boys (21.8 +/- 14.5 microg/l vs 8.9 +/- 10.6 micro/l, p =
      0.002). However, the difference for serum IGF-I levels was not significant
      between diabetic girls and boys (240.7 +/- 96.8 ng/ml vs 234.7 +/- 93.2 ng/ml; p
      > 0.05). In all subjects, leptin levels were correlated with CSC (p = 0.04), CSD
      (p = 0.04) and IEM (p = 0.01), and IGF-1 levels were only correlated with CSC (p
      = 0.01). Leptin did not show any correlation with ultrasonographic measurements
      in both girls and boys separately. IGF-1 was correlated with CSC (p = 0.001), CSD
      (p = 0.002) and IEM (p < 0.001) in boys but not in girls. In a multivariate
      regression model, IGF-1 emerged as independent correlates for mean CSD and IEM in
      boys but not in girls. CONCLUSION: Serum leptin and IGF-1 levels in children and
      adolescent patients with type 1 diabetes are associated with functions of common
      carotid artery, and the association of IGF-1 levels is influenced by sex.

PMID- 15456196
TI  - Effects of intralipid infusion on blood viscosity and other haemorheological
      parameters in neonates and children.
AB  - AIM: To study acute haemorheological effects of intralipid in preterm and full
      term neonates and children. Circulatory complications of intralipid infusion,
      such as increases in pulmonary and peripheral flow resistance, have been
      associated with impaired blood rheology. METHODS: During total parenteral
      nutrition, 10 preterm infants, 10 full-term neonates and 10 children received an
      initial dose of intralipid as continuous infusion (0.6 g/kg) over 4 h.
      Additionally, blood of 10 healthy preterm infants, 10 full-term neonates and 10
      adults was incubated with intralipid. Whole blood and plasma viscosity (capillary
      viscometer), red blood cell (RBC) deformability (rheoscope) and RBC aggregation
      (Myrenne aggregometer) were measured before and after intralipid infusion and
      before and after in vitro incubation of blood with intralipid. RESULTS: During
      intralipid infusion, plasma triglyceride levels increased from 0.13 +/- 0.27 to
      2.16 +/- 0.68 g/l in the preterm infants, from 0.14 +/- 0.21 to 1.64 +/- 0.54 g/l
      in the full-term neonates and from 0.65 +/- 0.31 to 2.26 +/- 0.60 g/l in the
      children. Whole blood viscosity decreased by about 10% after intralipid in all
      three groups due to similar decreases in haematocrit. RBC aggregation decreased
      by about 20% after intralipid infusion. Plasma proteins, plasma viscosity and RBC
      deformation were not affected by intralipid. In vitro incubation of blood with
      intralipid resulted in a marked reduction of RBC aggregation that was related to
      the intralipid concentration. At intralipid concentrations of 4 and 8 mg/ml, no
      RBC aggregation was noted in preterm and full-term neonates. In adults, RBC
      aggregation decreased by 50%. CONCLUSIONS: Previously described deleterious
      effects of intralipid on circulation can not be explained by changes in
      haemorheological properties.

PMID- 15456197
TI  - The natural course of gastro-oesophageal reflux.
AB  - Gastro-oesophageal reflux disease is a common phenomenon usually consistent with
      a benign prognosis. But alarm symptoms and complications occur at any age, and
      may be difficult to recognize clinically although requiring prompt and adequate
      intervention. Many unsettled issues in gastro-oesophageal reflux (disease) are
      encountered in its natural course and clinical presentation. Severity of reflux
      is much more related to complications than to the amount of reflux. Current
      medical reflux treatment with H2-receptor antagonists and preferably with proton
      pump inhibitors is efficient in controlling symptoms and healing oesophagitis.
      Whether early treatment of mild reflux significantly changes the incidence or
      severity of symptoms and complications in adulthood is uncertain. Atopic disease
      is now recognized to cause reflux-like symptoms. Paediatricians should adequately
      consider the impact on the quality of life of repetitive regurgitation.
      CONCLUSION: Further research is needed to define more clearly how many, which and
      why some children with reflux disease progress to persisting chronic disease and
      others do not.

PMID- 15456198
TI  - Characteristics and outcome of long-stay patients in a paediatric intensive care
      unit: a case-control study.
AB  - AIM: To identify differences in baseline characteristics and outcome between long
      stay and other patients admitted to a paediatric intensive care unit with the
      same diagnosis. METHODS: Over a period of 6 y, data of paediatric intensive care
      unit patients with a length of stay of 30 or more days (long-stay patients) and
      aged 1 to 18y were retrospectively collected. Long-stay patients were matched
      with the next patient who was admitted to the paediatric intensive care unit with
      the same diagnosis. Evaluated characteristics on admission included: age, sex,
      presence of chronic morbidity, functional status, Pediatric Risk of Mortality
      score, presence of multiple organ system failure and complications during
      admission. Outcome (survival and functional status) was assessed 2.5 to 8.5 y
      after admission. RESULTS: Of 19 long-stay patients identified, 15 could be
      matched with a control patient admitted with the same diagnosis. No significant
      difference in baseline characteristics was found between long-stay patients and
      the matched controls. The mean number of complications per long-stay patient was
      2.9, compared to 1.2 per control patient (p = 0.02). Infection accounted for half
      of the complications. Mortality rate in long-stay patients was not higher than in
      the matched controls (36.8 vs 26.7%, p = 0.54). Paediatric intensive care unit
      stay did not change functional status in either long-stay patients or controls.
      CONCLUSION: Long-stay patients in the paediatric intensive care unit had more
      complications, but baseline characteristics, mortality and functional outcome
      were not different from a control group admitted with the same diagnosis.

PMID- 15456199
TI  - Maternal-neonatal retinol and alpha-tocopherol serum concentrations in Greeks and
      Albanians.
AB  - BACKGROUND: Vitamin A and E are required in physiological processes such as
      pregnancy and growth. AIM: To evaluate retinol and alpha-tocopherol serum levels
      in Greek and Albanian mothers and in their newborns. METHODS: Data concerned 1125
      Greek and 898 Albanian mothers along with their newborns. Immediately after
      delivery, blood from the umbilical cord and from the mothers was collected into
      light-protected tubes. Retinol and alpha-tocopherol serum levels were measured
      with a reversed-phase HPLC method. A 60-d dietetic diary was kept by each woman
      during the last 2 mo of pregnancy. RESULTS: Retinol (1.3 +/- 0.1 micromol/l) and
      alpha-tocopherol (32.9 +/- 9.5 micromol/l) levels were estimated to be normal in
      Greek mothers and in most of their offspring (0.9 +/- 0.1 and 18.5 +/- 3.4
      micromol/l, respectively). In contrast, in Albanian mothers, retinol
      concentration was found to be low (0.6 +/- 0.1 micromol/l), and in 1/3
      significantly low (<0.45 micromol/l). Consequently, the vitamin was evaluated to
      be very low in their newborns (0.4 +/- 0.1 micromol/l), and in 1/2 extremely low.
      However, in 12% of the Albanian cord blood samples, retinol level was determined
      to be higher as compared with that of their mothers. alpha-Tocopherol was
      evaluated to be normal in most of the immigrant mothers (20.0 +/- 8.8 micromol/l)
      and low (<7.5 micromol/l) in 15% of their newborns. Vitamin A intake was found to
      be extremely low and vitamin E low (p < 0.05) in the Albanians. CONCLUSIONS: (a)
      The decreased vitamin A and vitamin E intake, and their low blood status in the
      Albanian mothers and in their newborns, could be due to their low socio-economic
      and nutritional status. (b) Immigrant Albanians, during their pregnancy, and
      their newborns should be "followed up", being at risk of developing symptoms from
      the very low levels of these lipid-soluble vitamins.

PMID- 15456200
TI  - Short-term outcome after active perinatal management at 23-25 weeks of gestation.
      A study from two Swedish tertiary care centres. Part 2: infant survival.
AB  - AIM: To determine neonatal survival rates based on both foetal (stillborn) and
      neonatal deaths among infants delivered at 23-25 wk, and to identify maternal and
      neonatal factors associated with survival. METHODS: The medical records of 224
      infants who were delivered in two tertiary care centres in 1992-1998 were
      reviewed retrospectively. At these centres, policies of active perinatal and
      neonatal management were universally applied. Data were analysed by gestational
      age groups and considered in three time periods. Logistic regression models were
      used to identify factors associated with survival. RESULTS: The rate of foetal
      death was 5%. Of infants born alive, 63% survived to discharge. Survival rates
      including foetal deaths in the denominator at 23, 24 and 25 wk were 37%, 61% and
      74%, respectively, and survival rates excluding foetal deaths were 43%, 63% and
      77%, respectively. Of infants born with 1-min Apgar scores of 0-1, 43% survived.
      In the total cohort, survival rates including foetal deaths in the denominator
      increased from 52% in time period 1 to 61% in time period 2 and 74% in time
      period 3 (p < 0.02). On multivariate logistic regression analysis, higher
      birthweight (OR: 1.91 per 100 g increment; 95% CI: 1.45-2.52), female gender (OR:
      3.33; 95% CI: 1.65-6.75), administration of antenatal steroids (OR: 2.95; 95% CI:
      1.46-5.98) and intrauterine referral from a peripheral hospital (OR: 2.35; 95%
      CI: 1.18-4.68) were associated with survival. Apgar score < or = 3 at 1 min (OR:
      0.46; 95% CI: 0.22-0.95) was associated with decreased survival. The use of
      antenatal steroids was protective at 23-24 wk (OR: 5.2; 95% CI: 2.0-13.7), but
      not at 25 wk. CONCLUSIONS: Active perinatal management that included universal
      initiation of neonatal intensive care virtually eliminated intrapartum
      stillbirths and delivery room deaths, and resulted in survival rates that compare
      favourably with those of recent studies. However, the policies of active care
      postponed death in non-survivors. Individual variations in outcome in relation to
      the infant's condition at birth as reflected by the Apgar scores preclude the
      making of treatment decisions in the delivery room.

PMID- 15456201
TI  - Short-term outcome after active perinatal management at 23-25 weeks of gestation.
      A study from two Swedish perinatal centres. Part 3: neonatal morbidity.
AB  - AIM: To determine major neonatal morbidity in surviving infants born at 23-25
      weeks, and to identify maternal and infant factors associated with major
      morbidity. METHODS: The medical records of 224 infants who were delivered at two
      tertiary care centres in 1992-1998 were reviewed retrospectively. At these
      centres, policies of active perinatal and neonatal management were universally
      applied. Of the 213 liveborn infants, 140 (66%) survived to discharge. Data were
      analysed by gestational age and considered in three time periods. Logistic
      regression models were used to identify factors associated with morbidity.
      RESULTS: Of the survivors, 6% had intraventricular haemorrhage grade > or = 3
      (severe IVH) or periventricular leukomalacia (PVL), 15% retinopathy of
      prematurity > or = stage 3 (severe ROP) and 36% bronchopulmonary dysplasia (BPD).
      On logistic regression analysis, severe IVH or PVL was associated with duration
      of mechanical ventilation (odds ratio, OR: 1.53 per 1-wk increment in duration;
      95% confidence interval, CI: 1.01-2.33). Severe ROP was associated with the
      presence of a patent ductus arteriosus (PDA) (OR: 3.31; 95% CI: 1.11-9.90) and
      birth in time period 3 versus time periods 1 and 2 combined (OR: 6.28; 95% CI:
      2.10-18.74). BPD was associated with duration of mechanical ventilation (OR: 2.71
      per 1-wk increment in duration; 95% CI: 1.76-4.18) and with the presence of any
      obstetric complication (OR: 2.67; 95% CI: 1.07-6.65). Gestational age and
      birthweight were not associated with major morbidity. Of all survivors, 81% were
      discharged home without severe IVH, PVL or severe ROP. CONCLUSIONS: Increased
      survival as a result of active perinatal and neonatal management was associated
      with favourable morbidity rates compared with those in recent studies. Among
      survivors born at 23-25 weeks, neither gestational age nor birthweight was a
      significant determinant of major morbidity.

PMID- 15456202
TI  - PCDDs, PCdfs and Co-PCBs in human breast milk samples collected in Tokyo, Japan.
AB  - AIM: To observe the distribution of PCDD/Fs and Co-PCBs in samples of human
      breast milk collected in Japan. METHODS: Using high-resolution gas
      chromatography, milk samples for polychlorinated dibenzo-p-dioxins (PCDDs; 14
      congeners), polychlorinated dibenzofurans (PCDFs; 15 congeners) and coplanar
      polychlorinated biphenyls (Co-PCBs; 12 congeners) from 240 mothers residing in
      Tokyo were analysed. There were 120 donors each of primiparae and secundiparae,
      each group including 60 donors aged 25 to 29 y ("the younger group") and 60 aged
      30 to 34 y ("the older group"). Individual milk samples (about 50 ml) were
      obtained 30 d after delivery in 1999 and in 2000. RESULTS: The mean toxic
      equivalent (TEQ) level of PCDD/Fs (the sum of PCDDs and PCDFs) was 14.9 pg TEQ/g
      fat, of Co-PCBs 10.6 pg TEQ/g fat, and the total sum of PCDD/Fs and Co-PCBs was
      25.6 pg TEQ/g fat. The mean TEQ levels of PCDD/Fs, Co-PCBs, and total PCDD/Fs and
      Co-PCBs were higher in primiparae than in secundiparae. In each of these, the
      levels were higher in the subgroup of older mothers. In the secundiparae, the
      mean levels were lower in the group of mothers who had breastfed their first
      babies than in those who bottle-fed or partly bottle-fed their first born.
      CONCLUSIONS: The concentrations of PCDD/Fs and Co-PCBs in the breast milk of
      Japanese women were slightly lower than those described in previous studies
      conducted in Japan and other countries; and the concentrations of PCDD/Fs and Co
      PCBs in the breast milk were influenced mainly by the mother's age and nursing
      history.

PMID- 15456203
TI  - Polychlorinated biphenyls in colostral milk and visual function at 12 months of
      life.
AB  - BACKGROUND AND AIMS: Environmental contaminants such as persistent organic
      chlorines and heavy metals, which are supplied to the foetus by transplacental
      transfer and to breastfed infants by the milk, may impair cognitive functions.
      Long-chain polyunsaturated fatty acids, which are known to enhance development
      during foetal life and early infancy, may counteract the toxic effect of
      environmental contaminants. In this study, we have investigated whether
      polychlorinated biphenyls (PCBs) impair early development of vision, and whether
      such impairment can be modulated by essential long-chain polyunsaturated fatty
      acids. MATERIAL: Healthy term infants born in Milan and its surroundings, and who
      were exclusively breastfed for at least 4 mo, were prospectively examined up to
      the age of 12 mo. METHODS: Samples from colostrums, the first 2 d after delivery,
      and of mature breast-milk after 1 and 3 mo were collected. The samples were
      analyzed for PCB 105, 118, 138, 153, 156 and 180 and for DDT and DDE. In all
      infants, the plasma levels of the long-chain polyunsaturated fatty acids (LC
      PUFAs), C18:2 n-6, C18:3 n-3, C20:4 n-6, C20:5 n-3 and C22:6 n-3 were analysed
      within the first three postnatal days. The PCB levels in colostral milk, as well
      as of LC-PUFAs in plasma, were considered to mirror perinatal supply. Visual
      function was evaluated by P100 with latency evoked potentials (VEPs) at 12 mo of
      age. Statistical analysis was based on simple and partial correlation
      coefficients (p < 0.05). RESULTS: On bivariate analysis, wave latency VEP at 15
      min was significantly related to the colostral levels of DDT, DDE and all
      examined PCBs except PCB 105 (with correlation coefficient r = 0.401 to 0.618),
      whereas P100 wave latency VEP at 60 min was related to DDT (r = 0.513) and PCB
      180 (r = 0.504). Infant plasma levels of C22:6 n-3 were inversely associated with
      P100 wave latency at 60 min (r = -0.418) and at 1Hz-2J (r = -0.466). After
      controlling for C22:6 n-3, the partial correlation coefficient of P100 wave
      latency VEP at 15 min to the colostral level of PCB 180 was 0.403 (p = 0.07).
      CONCLUSION: Within the population of this study, a weak relation was found
      between impaired visual function at 12 mo of age of healthy infants and the
      levels of PCBs, DDT and DDE in colostral milk. The effect of impairment was no
      longer evident after controlling for the plasma level of LC-PUFAs as found in the
      infant a few days after birth.

PMID- 15456204
TI  - Home breastfeeding support by health professionals: findings of a randomized
      controlled trial in a population of Italian women.
AB  - AIM: We conducted a randomized controlled trial to assess the effectiveness of a
      support intervention delivered by health professionals to increase the rate and
      duration of breastfeeding. METHODS: A randomized controlled intervention study
      was conducted in the period 2000-2001 among 605 mothers who had given birth in a
      public maternity ward located in the city of Rome, Italy. The intervention
      consisted of a home visit by a midwife from the maternity ward of the hospital.
      The outcome of the study was the infant's feeding habits, assessed by a 24-h
      recall. The effect of the intervention on the duration of breastfeeding was
      estimated by the Kaplan-Meier method and by the Cox multivariate regression
      model. RESULTS: According to intention-to-treat analysis, there was no
      significant difference between the intervention and the control group, after
      controlling for confounding factors (hazard ratio (HR) 1.04; 95% confidence
      interval (95% CI): 0.85-1.26). The duration of breastfeeding was shorter (HR
      1.61; 95% CI: 1.13-2.31) for women in the intervention group who refused the
      obstetric visit. CONCLUSION: Our study shows that an early home support programme
      delivered by health professionals was not effective in increasing breastfeeding
      initiation and duration.

PMID- 15456205
TI  - Factors associated with unconstrained growth among affluent Ghanaian children.
AB  - AIM: To identify socio-economic factors associated with unconstrained growth
      among children living in well-off neighbourhoods of Accra, Ghana. METHODS: A
      cross-sectional study involving the assessment of the anthropometric status of
      preschool children. Children (n = 309) between the ages of 12 and 23 mo who live
      in affluent communities in Accra, Ghana were recruited for the study. Weight,
      length and mid-upper arm circumference were taken. Information was collected on
      household demographics and socio-economic status, including parental education
      and household income. Associations between these variables and attained growth
      were analysed to establish cut-offs for screening children with unconstrained
      growth. RESULTS: The mean weight-for-age (WA), length-for-age (LA) and weight-for
      length (WL) Z-scores of the sub-sample selected on the basis of high socio
      economic criteria were -0.18, -0.40 and 0.16, respectively. Among these well-off
      children, 0% were underweight, 3.0% were stunted and 0% were wasted (Z-scores <
      2). Factors associated with better anthropometric status were paternal education
      and household income. Two screening criteria combining the two variables were
      selected: polytechnic education and income > 1,000,000 cedis (435 US dollars) or
      university education and income > 200,000 cedis. CONCLUSIONS: The children
      experiencing unconstrained growth belonged to a sub-population of affluent
      households characterized by high paternal education and household income. This
      subpopulation was targeted for screening for the WHO Multicentre Growth Reference
      Study in Ghana.

PMID- 15456206
TI  - Hantavirus Puumala infection as a cause of fever of unknown origin in a child.
AB  - Hantavirus infection due to Puumala virus causes nephropathica epidemica, a
      disorder characterized by fever, haematological abnormalities, mild renal
      dysfunction and ophthalmological abnormalities. The prevalence in most European
      countries is low, but the virus can be endemic. In children, hantavirus infection
      is rare. This paper describes a young girl diagnosed with hantavirus infection.
      The patient presented with high fever, proteinuria, haematuria and eye lesions,
      but other typical hallmarks of the disease, such as thrombocytopenia and renal
      dysfunction, were absent. This case report demonstrates the need to consider the
      diagnosis of hantavirus infection in children with prolonged fever of unknown
      origin. The diagnosis is based on serological tests.

PMID- 15456207
TI  - Low-dose acyclovir for HSV-2 meningitis in a child.
AB  - A 7-y-old girl with genital herpes following sexual abuse presented with dysuria,
      fever and meningeal signs. Acyclovir (15 mg/kg/d for 10 d) was administered for
      severe genitourinary symptoms. The CSF culture was positive for HSV type 2.
      Complete resolution of all symptoms demonstrates that, as in adults, HSV-2
      meningitis does not require high-dose or prolonged acyclovir therapy.

PMID- 15456208
TI  - Ethical issues in research on control of the HIV/AIDS epidemic: report from a
      workshop of the world federation of scientists, Erice, Sicily, Italy, 22-24
      August 2003.
AB  - In research on control of the HIV/AIDS epidemic there are many ethical issues to
      be considered. The problem of personal autonomy versus the interest of society to
      prevent the spread of the disease in various settings makes it difficult to
      follow the regulations of the Declaration of Helsinki in all respects. This is
      particularly clear in the evaluation of trials aimed at preventing mother-to
      child transmission of HIV. The interest of the child does not always conform to
      the policy of avoiding stigmatization of the mother. Programmes for the
      implementation of antiretroviral therapy and vaccine trials may differ in
      countries with different mean incomes of the inhabitants, and are also influenced
      by local patterns. For this reason, the Declaration of Helsinki should be changed
      in such a way that it conforms with the ways in which it may be possible to
      combat such a disastrous epidemic as that caused by HIV.

PMID- 15456209
TI  - Acquired methaemoglobinaemia.

PMID- 15456210
TI  - Every immune thrombocytopenia is not idiopathic thrombocytopenic purpura.

PMID- 15456211
TI  - Kikuchi's lymphadenitis presenting as an inguinal hernia in a 3-year-old girl.

PMID- 15456212
TI  - A rare coexistence of urogenital anomalies, anorectal atresia and skeletal
      defects.

PMID- 15456213
TI  - [Taxonomic analysis of Pseudomonas strains with uncertain taxonomic status].
AB  - Pseudomonas strains isolated from soil and rhizosphere and designated as
      "Pseudomonas rathonis", Pseudomonas sp. B and Pseudomonas sp. C have been
      characterized by 113 phenotypic properties and studied by methods of molecular
      genetic analysis. The 5'-terminal hypervariable 16S rRNA regions, containing from
      208 to 344 nucleotides have been amplified and sequenced. The comparative
      analysis of sequence results gave evidence about phylogenetic relatedness of
      studied bacteria (98-100% of 16S rRNA sequences identity) to some saprophytic and
      plant-pathogenic Pseudomonas species. The latter substantially differed from
      studied strains in phenotypic characteristics. The DNA-DNA hybridization results
      have shown the low (0-36%) level of chromosomic DNA homology of "Pseudomonas
      rathonis", Pseudomonas sp. B, Pseudomonas sp. C strains with the type strains of
      P. fluorescens, P. putida, P. mendocina, P. pseudoalcaligenes. Obtained data give
      evidence that these strains belong to some novel Pseudomonas species.

PMID- 15456214
TI  - [Effect of aboriginal populations of soy nodule bacteria on symbiotic activity of
      introduced strain Bradyrhizobium japonicum 634b].
AB  - The method of limit dilutions was used to determine the number of soy nodule
      bacteria in soils of different regions of Ukraine. Symbiotic properties of
      aboriginal populations of soy rhizobia have been studied under the conditions of
      vegetation researches, their effect on activity of the introduced strain B.
      japonicum 634b has been shown. Numerous aboriginal populations of soy nodule
      bacteria (200-3500 units per 1 g of soil) have been found in soils of fields
      where soy was sown during a long period of time. It is shown that they provide
      for the highest degree of plants infection. These populations can compete with
      the standard strain. Activity of formation of symbiotic apparatus in the variants
      with inoculation of B. japonicum 634b remains invariable or something decreases.
      It has been established that populations of nodule bacteria are not numerous (20
      units per 1 g of soil) or absolutely absent in the field soils where soy growing
      is only started. Seeds inoculation by the productive strain under conditions of
      these soils favours considerable increase of the number of nodules (1.3-22.0
      times) and their nitrogenase activity (1.2-1.9 times).

PMID- 15456215
TI  - [Multiple change of phenotype, conjugated with the loss of yellow pigmentation of
      Erwinia herbicola].
AB  - It has been shown that the loss of yellow pigmentation (phenotype Crt) of
      nonphotosynthesizing epiphyte bacterium Erwinia herbicola is accompanied by the
      loss of prototrophicity (phenotype Thi). Most Crt Thi-variants change the
      character of sensitivity to temperate erwiniophage E105 and bacteriocins
      (phenotype Ph/Bn). Some of them become sensitive to the killer effect of their
      own bacteriocins--autocins (phenotype Au). Multiple change of the phenotype in E.
      herbicola occurs so spontaneously as under variable growing of bacteria at the
      optimal and supraoptimal growth temperature. It is also established that the
      cells of one of the strains stop synthesizing the additional carotenoid or
      synthesize the changed products. It is shown that carotenoid synthesis in the
      cells of E. herbicola g157/5k may be reduced by means of transduction of the Crt
      phenotype by lipid-containing bacteriophage UA1. Multiple change of the phenotype
      connected with the loss of yellow pigmentation by E. herbicola was referred to
      the phenomenon of the population dissociation which is similar to that in E.
      carotovora.

PMID- 15456216
TI  - [Screening of the strains of lactic acid bacteria possessing hypocholesterinemic
      activity and their practical use].
AB  - The strains of lactic acid bacteria (n = 139) belonging to Lactobacillus,
      Streptococcus, Enterococcus and Leuconostoc genera have been studied. It has been
      shown that neither of the strains used cholesterol as a source of carbon. Some
      strains (13.6%) hydrolyzed actively the conjugates of bile acids. The hydrolyzed
      activity displayed to a higher extent in anaerobic conditions on the medium with
      glucose. Hydrolase of conjugates of bile salts, which precipitated under acid
      value of pH and were excreted from the organism, was contained in 29% of 69
      studied strains of lactic acid bacteria. Cholesterol is also removed from the
      organism under the same pH values that is confirmed by clinical tests of the
      product "Gerolakt Kislomolochny" (lactic-acid Gerolact).

PMID- 15456217
TI  - [Effect of chromium (VI) on growth physiology and sorptional capacity of yeast].
AB  - Resistance of 7 yeast species (7 strains) to various chrome concentrations in the
      medium and their sorptional activity have been studied. It is shown that the
      biomass of the yeast Williopsis californica UKM-248, Candida krusei UKM-61t under
      their concentration in the medium of 200 and 500 mg/l of Cr6+ is 0.74 and 0.45
      g/l DWB, respectively. For the rest of strains these chrome concentrations are
      toxical and the concentration of 100 mg/l of Cr6+ is the bordering threshold for
      them. Under periodical cultivation in the medium with 30 mg/l of Cr6+ one can
      observe the delay of cultures growth displayed in the increase of the lag-phase
      and exponential growth phase as well as the decrease of medium pH (to 2). The
      resistance of the studied yeast to high concentrations of Cr6+ correlates with
      their sorptional activity.

PMID- 15456218
TI  - [Effect of radio-frequency electromagnetic radiation on physiological features of
      Saccharomyces cerevisiae strain UCM Y-517].
AB  - Effect of electromagnetic radiation (40.68 MHz) on growth characteristics of
      Saccharomyces cerevisiae strain UCM Y-517 has been studied. Reliable increase of
      the specific growth rate (by 7-15%) and change of duration of growth phases as a
      result of irradiation of yeast population has been shown. The EMR effect has been
      found to depend on physiological state of the irradiated cells and composition of
      the irradiation performance medium: reliable effects were found only for the
      cells preliminarily grown on the dense nutrition medium in the late phase of
      delayed growth or on achieving the stationary growth phase. The role of radiation
      term and power as well as of temperature factor in EMR effect on the cells is
      discussed. It has been noted that the dependence of specific growth rate of yeast
      on the initial density of cells population acquire the nonlinear character as
      affected by EMR of radiofrequency range.

PMID- 15456219
TI  - [Features of amino acid assimilation by representatives of the Mycoplasma genus].
AB  - Amino acid assimilation by different representatives of Mycoplasma genus has been
      investigated. All typical strains, involved in this research--Mycoplasma
      pneumoniae, M. capricolum, M. hominis, M. mycoides subsp. capri, M. fermentans,
      M. salivarium were able to assimilate asparagine, glutamine, threonine, histidine
      and tryptophan. Most of the investigated mycoplasmas were able to assimilate
      proline, phenylalanine, methionine, glutamate, lysine, serine, tyrosine, glycine,
      valine, isoleucine and alanine; assimilation of leucine and cysteine was observed
      rarely. Each of the investigated species of mycoplasmas are characterized by a
      specific spectrum of assimilated amino acids that can be used as additional
      characteristic for systematics of mollicutes.

PMID- 15456220
TI  - [Features of solid materials' colonization by pure and mixed cultures of
      methanotrophs].
AB  - The process of colonization of hydrophilic (glass) and hydrophobic (polysterene)
      carriers by pure cultures of methanotrophs Methylocystis parvus UCM B-3490T,
      Methylococcus capsulatus UCM B-3030, as well as by their cultures mixed with
      Bacillus megaterium UCM B 5723T and Pseudomonas putida VKPM B-4188 under the
      conditions efficient for methanotrophic bacteria. M. parvus demonstrated the
      highest intensity of this process on the above carriers owing to high hydrophobic
      cell surface. Both methanotrophs colonized the glass surface more quickly with
      formation of microcolonies on carriers after 6 days of incubation in pure and
      mixed cultures with B. megaterium. The number of bacilli on these carriers
      quickly decreased. In the mixed cultures with P. putida the glass and polysterene
      colonization intensity decreased, while the amount of pseudomonas on carriers
      increased.

PMID- 15456221
TI  - [Stages of biofilm formation by sulfate-reducing bacteria].
AB  - Taxis to Fe3+ ions and adhesion to steel-3 of sulphate-reducing bacteria
      different by corrosion activity have been investigated. It has been shown that
      taxis activity of cells from the Postgate medium "B" was higher than from the
      buffer. Aggressive strains Desulfovibrio indonensis, Desulfovibrio sp. possessed
      higher activity taxis with respect to Fe3+ ions. It has been noted that
      aggressive strains of sulphate-reducing bacteria adhered more actively to the
      steel surface and formed more powerful proteins than nonagressive strains (19.4
      +/- 0.3 x 10(8) cell/cm2 in aggressive strain Kiev-10 and 3.4 +/- 0.1 x 10(8)
      cell/cm2 in nonaggressive strain Kiev-45). The authors have proposed a new
      approach to the study of microbe-induced corrosion with the use of thin metal
      matrices. This method permits estimating the corrosive effect on metal matrix of
      exopolymers of sulphate-reducing bacteria and showing that more aggressive
      strains of these bacteria lead in formation and functioning of the biofilm.

PMID- 15456222
TI  - [The course of virus infection of Lycopersicon esculentum plants at high
      concentrations of heavy metals].
AB  - Effect of certain compositions of heavy metals on the course of the system
      infection of TMV in plants of tomatoes Lycopersicon esculentum L. under field
      conditions was investigated. It is shown that the simultaneous influence of the
      virus infection and heavy metals in concentration of 10 MPC (maximum permissible
      concentration) resulted in the decrease of the content of total chlorophyll in
      the investigated plants by degradation of chlorophyll A; that was more
      considerable decrease as compared with separate influence of each of the factors.
      Treatment of plants by toxical concentrations of lead and zinc led to
      inconsiderable delay in development of the system TMV infection together with the
      increase of the virus content in plants 2 and more times, that evidences for the
      probable synergism in the action of the given heavy metals and virus infection.
      On the contrary, copper, though it decreased the content of total chlorophyll,
      manifested the protective properties and restricted essentially the virus
      accumulation in a plant as a whole.

PMID- 15456223
TI  - [Method for obtaining the basic factor of pathogenicity of Phytoplasma-
      extracellular fructose-1,6-bisphosphatase (on the model of the agent of pale
      green dwarfness of cereals in culture)].
AB  - A preparation with fructose-1,6-bisphosphatase (FBPase) activity has been
      isolated as a result of the five-stage treatment of the culture liquid obtained
      after growing the agent of pale-green dwarfness of cereals on the medium CM IMB
      72. After this enzyme treatment by means of hydrophobic chromatography on the
      column from Toyopearl HW-60 (the enzyme was obtained from the column with
      decrease of ammonium sulphate (AS) concentration in the eluating buffer to 0.8
      M), the preparation deprivation of AS on the column with Sephadex G-10 and
      substrate-dependent chromatography on the column with CM-sepharose the
      extracellular 176-fold purified FBPase. Acholeplasma laidlawii var. granulum
      strain 118 was obtained--the main pathogenicity factor for the agent of cereals
      yellow.

PMID- 15456224
TI  - The UNI/CARE perspective. Managing implementations. What we need to do
      differently.

PMID- 15456225
TI  - House building and system building.

PMID- 15456226
TI  - Implementation Guidelines... Do they change with time?

PMID- 15456227
TI  - If I knew then what I know now (or how I learned to live without sleep in two
      short years).

PMID- 15456228
TI  - Implementation timelines...A sample project plan outline.
AB  - You should let the project plan guide your course with established timelines.
      It's a wonderful tool for a process that in the end, what do you have? A dynamic,
      software application that will enhance your business by making each user's
      workload more streamlined and effective. The "timely" final result being a
      product that your employees and customers like and more importantly, the state
      approves.

PMID- 15456230
TI  - [Risky behavior in young persons].

PMID- 15456232
TI  - [The spoiled child. Affection and authority are not antinomic].

PMID- 15456233
TI  - [Childrens' place in contemporary society].

PMID- 15456234
TI  - [Devoured parents, devouring children].

PMID- 15456235
TI  - [The spoiled child, a tyranny that can be strangled in the crib].

PMID- 15456236
TI  - [Knowing how to say no].

PMID- 15456237
TI  - [Admission of children in Sweden].

PMID- 15456238
TI  - [III--Differed emergencies. 6/ Ovarian cysts--testicular torsion].

PMID- 15456239
TI  - [3/5 The legal responsibilities of nurses' aides].

PMID- 15456240
TI  - Novel arylsulfoanilide-oxindole hybrid as an anticancer agent that inhibits
      translation initiation.
AB  - Structure-activity relationship studies of substituted arylsulfoanilides as
      antiproliferatives, which are mediated by the partial depletion of intracellular
      Ca(2+) stores, resulted in the identification of compounds with micromolar
      activity against lung cancer cells in a growth inhibition assay. Incorporating
      the substitution pattern of the best arylsulfoanilides onto the 3-phenyloxindole
      scaffold resulted in a potent arylsulfoanilide-oxindole hybrid, 27. Compound 27
      inhibits cancer cell growth by partial depletion of intracellular Ca(2+) stores
      and phosphorylation of eIF2alpha.

PMID- 15456241
TI  - Inhibiting human astrocytoma growth: structure-activity relationships in
      neurostatin related glycolipids.
AB  - Neurostatin, a mammalian brain inhibitor of division of astroblast and
      astrocytoma cells, was characterized as the disialoganglioside GD1b, 9-O
      acetylated on the outer sialic acid residue (Galbeta1-->3GalNAcbeta1-->4(9-O-Ac
      NeuAcalpha2-->8NeuAcalpha2-->3)Galbeta1-->4Glcbeta1-->1'-ceramide). Using
      semisynthetic approaches, we prepared and tested different gangliosides O
      acetylated in the sialic acid and compared them to non-O-acetylated partners as
      inhibitors of U-373 glioma cells. Athough the O-acetylation of the sialic acid
      was the most important molecular feature for the antiproliferative activity of O
      acetylated gangliosides, monosaccharide links Galbeta1--> 3GalNAcbeta1 and
      NeuAcalpha2-->8NeuAcalpha2 enhanced the inhibitory activity.

PMID- 15456242
TI  - 11beta-alkyl-Delta9-19-nortestosterone derivatives: high-affinity ligands and
      potent partial agonists of the androgen receptor.
AB  - We report the synthesis of novel steroidal androgen receptor ligands comprising
      11beta-alkyl-Delta(9)-derivatives of 19-nortestosterone. These compounds are
      structurally related to the antiprogestin, antiglucocorticoid, and antiandrogen
      drug mifepristone (RU486). Nortestosterone analogues bearing 11beta-octyl and
      11beta-decyl side-chains bind tightly to recombinant AR protein (IC(50) = 6.6 nM
      and IC(50) = 0.8 nM), block AR dimerization, exhibit activity against LNCaP
      prostate cancer cells, and comprise partial AR agonists with low
      antiglucocorticoid activity.

PMID- 15456243
TI  - Structure-based discovery of nonpeptidic small organic compounds to block the T
      cell response to myelin basic protein.
AB  - We have utilized a computational structure-based approach to identify nonpeptidic
      small organic compounds that bind to a human leukocyte antigen (HLA) DR1301
      molecule (HLA-DR1301 or DR1301) and block the presentation of myelin basic
      protein peptide 152-165 (MBP 152-165) to T cells. A three-dimensional (3D)
      structure of DR1301 was derived by homology modeling followed by extensive
      molecular dynamics simulation for structural refinement. Computational structure
      based database searching was performed to identify nonpeptidic small-molecule
      candidates from the National Cancer Institute (NCI) database containing over 150
      000 compounds that can effectively interact with the peptide-binding groove of
      the HLA molecule. By in vitro testing of 106 candidate small molecules, two lead
      compounds were confirmed to specifically block IL-2 secretion by DR1301
      restricted T cells in a dose-dependent and reversible manner. The specificity of
      blocking DR1301-restricted MBP presentation was further validated in a binding
      assay using an analogue of the most potent lead compound. Computational docking
      was performed to predict the three-dimensional binding model of these confirmed
      small molecule blockers to the DR1301 molecule and to gain structural insight
      into their interactions. Our results suggest that computational structure-based
      searching is an effective approach to discover nonpeptidic small organic
      compounds to block the interaction between DR1301 and T cells. The nonpeptidic
      small organic compounds identified in this study are useful pharmacological tools
      to study the interactions between HLA molecules and T cells and a starting point
      for the development of a novel therapeutic strategy for the treatment of multiple
      sclerosis (MS) or other immune-related disorders.

PMID- 15456244
TI  - Cyclohexylcarbamic acid 3'- or 4'-substituted biphenyl-3-yl esters as fatty acid
      amide hydrolase inhibitors: synthesis, quantitative structure-activity
      relationships, and molecular modeling studies.
AB  - Fatty acid amide hydrolase (FAAH) is a promising target for modulating
      endocannabinoid and fatty acid ethanolamide signaling, which may have important
      therapeutic potential. We recently described a new class of O-arylcarbamate
      inhibitors of FAAH, including the cyclohexylcarbamic acid biphenyl-3-yl ester
      URB524 (half-maximal inhibitory concentration, IC(50) = 63 nM), which have
      significant anxiolytic-like properties in rats. In the present study, by
      introducing a selected group of substituents at the meta and para positions of
      the distal phenyl ring of URB524, we have characterized structure-activity
      profiles for this series of compounds and shown that introduction of small polar
      groups in the meta position greatly improves inhibitory potency. Most potent in
      the series was the m-carbamoyl derivative URB597 (4i, IC(50) = 4.6 nM).
      Furthermore, quantitative structure-activity relationship (QSAR) analysis of an
      extended set of meta-substituted derivatives revealed a negative correlation
      between potency and lipophilicity and suggested that small-sized substituents may
      undertake polar interactions with the binding pocket of the enzyme. Docking
      studies and molecular dynamics simulations, using the crystal structure of FAAH,
      indicated that the O-biphenyl scaffold of the carbamate inhibitors can be
      accommodated within a lipophilic region of the substrate-binding site, where
      their folded shape mimics the initial 10-12 carbon atoms of the arachidonyl
      moiety of anandamide (a natural FAAH substrate) and methyl arachidonyl
      fluorophosphonate (a nonselective FAAH inhibitor). Moreover, substituents at the
      meta position of the distal phenyl ring can form hydrogen bonds with atoms
      located on the polar section of a narrow channel pointing toward the membrane
      associated side of the enzyme. The structure-activity characterization reported
      here should help optimize the pharmacodynamic and pharmacokinetic properties of
      this class of compounds.

PMID- 15456245
TI  - Rationale, design, and synthesis of novel phenyl imidazoles as opioid receptor
      agonists for gastrointestinal disorders.
AB  - A small series of novel, imidazoles 4 have been prepared that exhibit very good
      binding affinities for the delta and mu opioid receptors (ORs), as well as
      demonstrate potent agonist functional activity at the delta OR. Representative
      imidazole 4a (K(i) delta = 0.9 nM; K(i) mu = 55 nM; K(i) kappa = 124 nM; EC(50)
      delta =13-25 nM) was further profiled for OR related in vivo effects. Compound 4a
      reduced gastrointestinal (GI) propulsive motility in a dose-dependent and
      naloxone-reversible manner, based on the results of the mouse glass bead
      expulsion test (3, 5, and 10 mg/kg, ip) and the mouse fecal pellet output test (1
      and 3 mg/kg, ip). Compound 4a showed no analgesic activity as measured by the
      mouse abdominal irritant test (MAIT) when dosed at 100 mg/kg, sc, but did show
      significant MAIT activity at doses of both 10 microg (40% inhibition) and 100
      microg (100% inhibition) when dosed intracerebroventricularly (icv). Taken
      together, these in vivo results suggest that 4a acts peripherally when dosed
      systemically, and that these prototypical compounds may prove promising as
      medicinal leads for GI indications.

PMID- 15456246
TI  - Design and synthesis of aryl diphenolic azoles as potent and selective estrogen
      receptor-beta ligands.
AB  - New diphenolic azoles as highly selective estrogen receptor-beta agonists are
      reported. The more potent and selective analogues of these series have comparable
      binding affinities for ERbeta as the natural ligand 17beta-estradiol but are >100
      fold selective over ERalpha. Our design strategy not only followed a traditional
      SAR approach but also was supported by X-ray structures of ERbeta cocrystallized
      with various ligands as well as molecular modeling studies. These strategies
      enabled us to take advantage of a single conservative residue substitution in the
      ligand-binding pocket, ERalpha Met(421) --> ERbeta Ile(373), to optimize ERbeta
      selectivity. The 7-position-substituted benzoxazoles (Table 5) were the most
      selective ligands of both azole series, with ERB-041 (117) being >200-fold
      selective for ERbeta. The majority of ERbeta selective agonists tested that were
      at least approximately 50-fold selective displayed a consistent in vivo profile:
      they were inactive in several models of classic estrogen action (uterotrophic,
      osteopenia, and vasomotor instability models) and yet were active in the HLA-B27
      transgenic rat model of inflammatory bowel disease. These data suggest that
      ERbeta-selective agonists are devoid of classic estrogenic effects and may offer
      a novel therapy to treat certain inflammatory conditions.

PMID- 15456247
TI  - A 4'-C-ethynyl-2',3'-dideoxynucleoside analogue highlights the role of the 3'-OH
      in anti-HIV active 4'-C-ethynyl-2'-deoxy nucleosides.
AB  - 4'-C-ethynyl-2'-deoxynucleosides belong to a novel class of nucleoside analogues
      endowed with potent activity against a wide spectrum of HIV viruses, including a
      variety of resistant clones. Although favorable selectivity indices were reported
      for several of these analogues, some concern still exists regarding the 3'-OH
      group and its role in cellular toxicity. To address this problem, we removed the
      3'-OH group from 4'-C-ethynyl-2'-deoxycytidine (1a). This compound was chosen
      because of its combined high potency and low selectivity index. The removal of
      the 3'-OH was not straightforward; it required a different synthetic approach
      from the one used to synthesize the parent compound. Starting with glycidyl-4
      methoxyphenyl ether, the target 4'-C-ethynyl-2',3'-dideoxycytidine analogue (rac
      1h) was obtained after 13 steps. In a cellular assay, rac-1h was completely
      inactive (0.001-10 microM) against HIV(LAI), demonstrating the critical
      importance of the 3'-OH for antiviral activity. To determine whether the role of
      the 3'-OH was essential for the phosphorylation of the compound by cellular
      kinases or for inhibition of DNA polymerization, we synthesized and tested the 5'
      triphosphate (rac-1h-TP) for its ability to inhibit HIV reverse transcriptase
      (RT). rac-1h-TP was slightly more potent than AZT-5'-triphosphate against wild
      type HIV RT, suggesting that the role of the 3'-OH is crucial only for the
      activation of the drug by cellular kinases. The lipase-catalyzed resolution of
      rac-1h into ent-1h (beta-D-dideoxyribo) and ent-14 (beta-L-dideoxyribo) and the
      synthesis of the corresponding 5'-triphosphates established the stereochemical
      assignment based on HIV RT's preference for the beta-D-enantiomer, which was
      confirmed by assaying against the M184V variant, an RT mutant with a marked
      preference for incorporating nucleosides in the D-configuration.

PMID- 15456248
TI  - Potent and selective ketoamide-based inhibitors of cysteine protease, cathepsin
      K.
AB  - Cathepsin K, a lysosomal cysteine protease of the papain superfamily, is
      abundantly and selectively expressed in osteoclasts, suggesting that this enzyme
      is crucial for bone resorption. Prevention of osteoclast-mediated bone resorption
      via inhibition of cathepsin K could be an effective approach to prevent
      osteoporosis. Potent and selective reversible ketoamide-based inhibitors have
      been identified in the present study. Using a known crystal structure of a
      ketoamide-based inhibitor, information from residues that form the P2/P3 pocket
      was used in the design of inhibitors that could allow for gains in selectivity
      and potency. Further, incorporation of P' selective heterocycles, along with the
      P2/P3 modifications, is also described. These modifications have resulted in
      potent and selective cathepsin K inhibitors that allow for improvements in their
      physiochemical properties and represent a viable lead series for the discovery of
      new therapies for the prevention and treatment of osteoporosis

PMID- 15456249
TI  - Ketoamide-based inhibitors of cysteine protease, cathepsin K: P3 modifications.
AB  - Osteoporosis is a disease characterized by skeletal fragility. Cathepsin K, a
      lysosomal cysteine protease, has been implicated in the osteoclast mediated bone
      resorption. Inhibitors of this protease could potentially treat this skeletal
      disease. The present work describes exploration of the spatial requirements of
      the S3 subsite by the use of various sterically demanding P3 substituents. Sulfur
      and oxygen linked heterocycles as well as those without heteroatom linkers were
      found to provide potent inhibitors of cathepsin K. Representative examples from
      these series also afforded quite good selectivity ratios against most cathepsins
      tested. The tolerability of the S3 subsite for sterically demanding groups that
      provide potency and selectivity enhances the attractiveness of P3 changes to
      improve the physiochemical properties of inhibitors in the developments of
      compounds for the treatment of osteoporosis.

PMID- 15456250
TI  - Identification of a new scaffold for opioid receptor antagonism based on the 2
      amino-1,1-dimethyl-7-hydroxytetralin pharmacophore.
AB  - The trans-(3,4)-dimethyl-4-(3-hydroxyphenyl)piperidines are a unique class of
      opioid antagonists that have recently provided selective antagonists for mu
      opioid receptors (MOR) and kappa-opioid receptors (KOR). Molecular modeling
      indicated a strong structural similarity between the parent of this series and 2
      amino-1,1-dimethyl-7-hydroxytetralin. In binding and in vitro functional assays,
      the aminotetralin derivatives displayed some overlap in SAR with that previously
      reported for the phenylpiperidine series, providing evidence for a common binding
      mode for the two series at opioid receptors. Introduction of a methoxy group in
      the 3-position increased potency at MOR and KOR receptors, suggesting that this
      aminotetralin skeleton can be utilized as a new scaffold for the design of
      selective opioid receptor antagonists.

PMID- 15456251
TI  - Soft docking and multiple receptor conformations in virtual screening.
AB  - Protein conformational change is an important consideration in ligand-docking
      screens, but it is difficult to predict. A simple way to account for protein
      flexibility is to soften the criterion for steric fit between ligand and
      receptor. A more comprehensive but more expensive method would be to sample
      multiple receptor conformations explicitly. Here, these two approaches are
      compared. A "soft" scoring function was created by attenuating the repulsive term
      in the Lennard-Jones potential, allowing for a closer approach between ligand and
      protein. The standard, "hard" Lennard-Jones potential was used for docking to
      multiple receptor conformations. The Available Chemicals Directory (ACD) was
      screened against two cavity sites in the T4 lysozyme. These sites undergo small
      but significant conformational changes on ligand binding, making them good
      systems for soft docking. The ACD was also screened against the drug target
      aldose reductase, which can undergo large conformational changes on ligand
      binding. We evaluated the ability of the scoring functions to identify known
      ligands from among the over 200 000 decoy molecules in the database. The soft
      potential was always better at identifying known ligands than the hard scoring
      function when only a single receptor conformation was used. Conversely, the soft
      function was worse at identifying known leads than the hard function when
      multiple receptor conformations were used. This was true even for the cavity
      sites and was especially true for aldose reductase. To test the multiple
      conformation method predictively, we screened the ACD for molecules that
      preferentially docked to the expanded conformation of aldose reductase, known to
      bind larger ligands. Six novel molecules that ranked among the top 0.66% of hits
      from the multiple-conformation calculation, but ranked relatively poorly in the
      soft docking calculation, were tested experimentally for enzyme inhibition. Four
      of these six inhibited the enzyme, the best with an IC(50) of 8 microM. Although
      ligands can get better scores in soft docking, the same is also true for decoys.
      The improved ranking of such decoys can come at the expense of true ligands.

PMID- 15456252
TI  - Identification and characterization of small molecule inhibitors of the calcium
      dependent S100B-p53 tumor suppressor interaction.
AB  - The binding of S100B to p53 down-regulates wild-type p53 tumor suppressor
      activity in cancer cells such as malignant melanoma, so a search for small
      molecules that bind S100B and prevent S100B-p53 complex formation was undertaken.
      Chemical databases were computationally searched for potential inhibitors of
      S100B, and 60 compounds were selected for testing on the basis of energy scoring,
      commercial availability, and chemical similarity clustering. Seven of these
      compounds bound to S100B as determined by steady state fluorescence spectroscopy
      (1.0 microM < or = K(D) < or = 120 microM) and five inhibited the growth of
      primary malignant melanoma cells (C8146A) at comparable concentrations (1.0
      microM < or = IC(50) < or = 50 microM). Additionally, saturation transfer
      difference (STD) NMR experiments confirmed binding and qualitatively identified
      protons from the small molecule at the small molecule-S100B interface.
      Heteronuclear single quantum coherence (HSQC) NMR titrations indicate that these
      compounds interact with the p53 binding site on S100B. An NMR-docked model of one
      such inhibitor, pentamidine, bound to Ca(2+)-loaded S100B was calculated using
      intermolecular NOE data between S100B and the drug, and indicates that
      pentamidine binds into the p53 binding site on S100B defined by helices 3 and 4
      and loop 2 (termed the hinge region).

PMID- 15456253
TI  - Frontal affinity chromatography with MS detection of EphB2 tyrosine kinase
      receptor. 1. Comparison with conventional ELISA.
AB  - FAC-MS offers a convenient method for measuring the relative binding strengths of
      ligands in a mixture and enables a rapid ranking and identification of ligands in
      the mixture as potential hits against immobilized targets. Using immobilized
      EphB2 receptor tyrosine kinase as the target and known kinase inhibitors, the
      results of FAC-MS screening (% shift) have been shown to correlate with the
      binding constant, K(d), and with IC(50) results from the more traditional ELISA
      assay. Therefore, since FAC-MS can accommodate a wide variety of target proteins,
      its applications could play a broad role in drug discovery not only at the hit
      discovery stage but also during the subsequent more rigorous screening at the hit
      to-lead and lead optimization stages.

PMID- 15456254
TI  - Further structurally constrained analogues of cis-(6-benzhydrylpiperidin-3
      yl)benzylamine with elucidation of bioactive conformation: discovery of 1,4
      diazabicyclo[3.3.1]nonane derivatives and evaluation of their biological
      properties for the monoamine transporters.
AB  - Our structure-activity relationship (SAR) study on piperidine analogues for
      monoamine transporters led to the development of a series of 3,6-disubstituted
      piperidine derivatives, structurally constrained versions of flexible piperidine
      analogues, with preferential affinity for the dopamine transporter (DAT). In our
      attempt to further rigidify this structure to study influence of rigidity on
      binding and in vivo activity, we have developed a series of 4,8-disubstituted 1,4
      diazabicyclo[3.3.1]nonane derivatives. All synthesized derivatives were tested
      for their affinity at the DAT, serotonin transporter (SERT), and norepinephrine
      transporter (NET) in the brain by measuring their potency in competing for the
      binding of [(3)H]WIN 35, 428, [(3)H]citalopram, and [(3)H]nisoxetine,
      respectively. Selected compounds were also tested for their ability to inhibit
      uptake of [(3)H]DA. The SAR study led to the discovery of a potent lead compound
      (-)-S,S-10c which exhibited high affinity and selectivity for the DAT (IC(50) =
      22.5 nM; SERT/DAT = 384 and NET/DAT > 444). It is interesting to note that both (
      )-10c and the lead compound from the 3,6-disubstituted series (-)-2 exhibited
      highest activity in their (S,S) isomer indicating similar requirement of
      regiospecificity for maximum interaction. Overall, our current SAR results
      corresponded well with the results from less constrained 3,6-disubstituted
      versions of these molecules albeit the former class exhibited more stringent
      requirement in molecular structure for activity. However, the potent compounds in
      the current series exhibited greater selectivity for the DAT compared to their
      corresponding lesser constrained 3,6-disubstituted versions indicating an effect
      of rigidity in selective interaction with the transporter proteins. In an effort
      to elucidate the bioactive conformational structure of the lead molecules in the
      current and the 3,6-disubstituted series, a preliminary molecular modeling study
      was carried out where the most rigid derivative (-)-10c was used as a template
      structure. Compounds (-)-2 and (-)-10c exhibited stimulant activity in locomotor
      tests in mice in which (-)-2 exhibited a slower onset and longer duration of
      action compared to (-)-10c. Both compounds occasioned complete cocaine-like
      responding in mice trained to discriminate 10 mg/kg ip cocaine from vehicle.

PMID- 15456255
TI  - Hydrogen bonding interactions of covalently bonded fluorine atoms: from
      crystallographic data to a new angular function in the GRID force field.
AB  - Through the years the GRID force field has been tuned to fit experimental
      observations in crystal structures. This paper describes the determination of the
      hydrogen bonding pattern for organic fluorines based on an exhaustive inspection
      of the Protein Data Bank. All the PDB complexes, whose protein structures have
      cocrystallized fluorine-containing ligands, were examined and geometrically
      inspected. By applying statistics, the hydrogen bonding geometry was described as
      a distribution function of the angle at the fluorine: a new specific angular
      function was consequently defined and inserted in the program GRID to estimate
      the effect of fluorine hydrogen bonds on the ligand-protein binding. All the
      fluorine-containing ligands collected from the PDB were docked within their
      corresponding protein binding sites: introducing the fluorine hydrogen bonding
      contribution improves the results of the docking experiments in terms of accuracy
      and ranking.

PMID- 15456256
TI  - Effects of altering the electronics of 2-methoxyestradiol on cell proliferation,
      on cytotoxicity in human cancer cell cultures, and on tubulin polymerization.
AB  - A series of new analogues of 2-methoxyestradiol (1) were synthesized to further
      elucidate the relationships between structure and activity. The compounds were
      designed to diminish the potential for metabolic deactivation at positions 2 and
      17 and were analyzed as inhibitors of tubulin polymerization and for
      cytotoxicity. 17alpha-methyl-beta-estradiol (30), 2-propynyl-17alpha
      methylestradiol (39), 2-ethoxy-17-(1'-methylene)estra-1,3,5(10)-triene-3-ol (50)
      and 2-ethoxy-17alpha-methylestradiol (51) showed similar or greater tubulin
      polymerization inhibition than 2-methoxyestradiol (1) and contained moieties that
      are expected to inhibit deactivating metabolic processes. All of the compounds
      tested were cytotoxic in the panel of 55 human cancer cell cultures, and
      generally, the derivatives that displayed the most activity against tubulin were
      also the most cytotoxic.

PMID- 15456257
TI  - Antitumor agents. 234. Design, synthesis, and biological evaluation of novel
      4beta-[(4' '-benzamido)-amino]-4'-o-demethyl-epipodophyllotoxin derivatives.
AB  - A series of 4beta-[(4' '-benzamido)-amino]-4'-O-demethyl-epipodophyllotoxin
      derivatives (11-23) were designed to enhance DNA topoisomerase II inhibition,
      overcome drug resistance, and modulate water solubility of etoposide (1)
      analogues. The target compounds were synthesized and evaluated for their effects
      against DNA topoisomerase II and KB or 1-resistant KB-7d tumor cells in tissue
      culture. As compared with 1, most compounds showed superior inhibition against
      both KB and KB-7d cells. Nine compounds (13-18, 20-22) induced higher levels of
      cellular protein-linked DNA breaks than did 1. Ten compounds selected from these
      and related derivatives were further examined for their antitumor spectra and
      drug-resistance profiles. Like 1, these compounds selectively inhibited the
      growth of KB (nasopharyngeal) and 1A9 (ovarian) tumor cells. More notably, they
      retained inhibitory activity against etoposide-, camptothecin-, and paclitaxel
      resistant KB or 1A9 subclones. In general, these C(4)-modified new derivatives
      exhibited superior activity profiles, particularly against drug-resistant cell
      lines, to those of 1. Preliminary metabolism studies on compounds 16 and 20
      revealed that 20 was relatively resistant to metabolism by rat serum and liver
      enzymes, while 16 was metabolically unstable.

PMID- 15456258
TI  - Inhibition of isoprene biosynthesis pathway enzymes by phosphonates,
      bisphosphonates, and diphosphates.
AB  - We have investigated the docking of a variety of inhibitors and substrates to the
      isoprene biosynthesis pathway enzymes farnesyl diphosphate synthase (FPPS),
      isopentenyl diphosphate/dimethylallyl diphosphate isomerase (IPPI) and
      deoxyxylulose-5-phosphate reductoisomerase (DXR) using the Lamarckian genetic
      alogorithm program, AutoDock. The docked ligand structures are predicted with a
      approximately 0.8 A rms deviation from the structures determined
      crystallographically. The errors found are a function of the number of atoms in
      the ligand (R = 0.91, p < 0.0001) and, to a lesser extent, on the resolution of
      the crystallographic structure (R = 0.70, p < 0.008). The structures of three
      isoprenoid diphosphates docked to the FPPS enzyme reveal strong electrostatic
      interactions with Mg(2+), lysine and arginine active site residues. Similar
      results are obtained with the docking of four IPPI inhibitors to the IPPI enzyme.
      The DXR substrate, deoxyxylulose-5-phosphate, is found to dock to Mn(2+)-NADPH
      DXR in an almost identical manner as does the inhibitor fosimdomycin to Mn(2+)
      DXR (ligand heavy atom rms deviation = 0.90 A) and is poised to interact with
      NADPH. Bisphosphonate inhibitors are found to bind to the allylic binding sites
      in both eukaryotic and prokaryotic FPPSs, in good accord with recent
      crystallographic results (a 0.4 A rms deviation from the X-ray structure with the
      E. coli enzyme). Overall, these results show for the first time that the
      geometries of a broad variety of phosphorus-containing inhibitors and substrates
      of isoprene biosynthesis pathway enzymes can be well predicted by using
      computational methods, which can be expected to facilitate the design of novel
      inhibitors of these enzymes.

PMID- 15456259
TI  - Modeling the protonation states of the catalytic aspartates in beta-secretase.
AB  - Beta-secretase (BACE) is a critical enzyme in the production of beta-amyloid, a
      protein that has been implicated as a potential cause of Alzheimer's disease
      (AD). There are two aspartic acid residues (Asp 32 and Asp 228) present in the
      catalytic region of BACE that can adopt multiple protonation states. The
      protonation state and precise location of the protons for these two residues,
      particularly in the presence of an inhibitor, are subjects of great interest
      since they have a direct bearing on the mechanism of aspartyl proteases and
      efforts to model beta-secretase. We have carried out full liner-scaling quantum
      mechanical (QM) calculations that include Poisson-Boltzmann solvation in order to
      identify the preferred protonation state and proton location in the presence and
      absence of an inhibitor. These calculations favor the monoprotonated state in the
      presence of ligand, and di-deprotonated state in the absence of ligand. Further
      the proton in the monoprotonated state is located on the inner oxygen of Asp 228.
      These results have implications for the catalytic mechanism of BACE and related
      aspartyl proteases. They also provide a reference state for the protein in
      structure-based modeling studies of this therapeutically important target.

PMID- 15456260
TI  - Synthesis and conformational analysis of a non-amidine factor Xa inhibitor that
      incorporates 5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine as S4 binding
      element.
AB  - Our exploratory study was based on the concept that a non-amidine factor Xa (fXa)
      inhibitor is suitable for an orally available anticoagulant. We synthesized and
      evaluated a series of N-(6-chloronaphthalen-2-yl)sulfonylpiperazine derivatives
      incorporating various fused-bicyclic rings containing an aliphatic amine expected
      to be S4 binding element. Among this series, 5-methyl-4,5,6,7
      tetrahydrothiazolo[5,4-c]pyridine type 61 displayed orally potent anti-fXa
      activity and evident prolongation of prothrombin time (PT) with the moderate
      bioavailability in rats. The X-ray crystal analysis afforded an obvious binding
      mode that 5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine and 6
      chloronaphthalene respectively bound to S4 and S1 subsites. In this X-ray study,
      we discovered a novel intramolecular S-O close contact. Ab initio energy
      calculations of model compounds deduced that conformers with the most close S-O
      proximity were most stable. The Mulliken population analysis proposed that this
      energy profile was caused by both of electrostatic S-O affinity and N-O
      repulsion. The results of these calculations and X-ray analysis suggested a
      possibility that the restricted conformation effected the affinity to S4 subsite
      of fXa.

PMID- 15456261
TI  - Long hydrocarbon chain ether diols and ether diacids that favorably alter lipid
      disorders in vivo.
AB  - Long hydrocarbon chain ethers with bis-terminal hydroxyl or carboxyl groups have
      been synthesized and evaluated for their potential to favorably alter lipid
      disorders including metabolic syndrome. Compounds were assessed for their effects
      on the de novo incorporation of radiolabeled acetate into lipids in primary
      cultures of rat hepatocytes as well as for their effects on lipid and glycemic
      variables in female obese Zucker fatty rats following 1 and 2 weeks of daily oral
      administration. The most active compounds were found to be symmetrical with four
      to five methylene groups separating the central ether functionality and the gem
      dimethyl or methyl/aryl substituents. Biological activity was found to be
      greatest for tetramethyl-substituted ether diols (e.g., 28 and 31), while
      bis(arylmethyl) derivatives (e.g., 10, 11, and 27), diethers (e.g., 49, 50, and
      56), and diphenyl ethers (e.g., 35 and 36) were the least active. For the most
      biologically active compound 28, we observed as much as a 346% increase in serum
      HDL-cholesterol and a 71% reduction in serum triglycerides at the highest dose
      administered (100 mg/kg) after 2 weeks of treatment. For compound 31 we observed
      a 69% reduction in non-HDL-cholesterol, accompanied by a 131% increase in HDL
      cholesterol and an 84% reduction in serum triglycerides under the same treatment
      conditions.

PMID- 15456262
TI  - Synthesis and evaluation of the affinity toward mu-opioid receptors of atypical,
      lipophilic ligands based on the sequence c[-Tyr-Pro-Trp-Phe-Gly-].
AB  - An ultimate and general model describing the interaction between opioid ligands
      and mu-opioid receptors is not available yet, so the mode of action of atypical
      peptide analogues or peptidomimetics is worthy of investigation. In this context,
      the peptide c[-Tyr-d-Pro-d-Trp-Phe-Gly-] was observed to act as an agonist toward
      mu-opioid receptors with appreciable potency, albeit deprived of a protonable
      nitrogen. This compound was synthesized as a member of a library of diastereo- or
      enantiomeric cyclic peptides based on the sequence of endomorphin-1, aiming to
      obtain lipophilic peptide ligands active at the mu-opioid receptors, having good
      performances in terms of resistance to enzymatic degradation and permeation of
      biological barriers.

PMID- 15456263
TI  - Toward a novel metal-based chemotherapy against tropical diseases. 7. Synthesis
      and in vitro antimalarial activity of new gold-chloroquine complexes.
AB  - A number of new Au(I) and Au(III) complexes of chloroquine (CQ) have been
      prepared, characterized, and evaluated in vitro against several strains of
      Plasmodium falciparum. [(CQ)Au(PPh(3))][NO(3)] (2) was synthesized by reaction of
      AuCl(PPh(3)) with AgNO(3) followed by treatment with CQ. Similar reactions of
      AuCl(PR(3)) (R = Me, Et) with KPF(6) and CQ yielded [(CQ)Au(PMe(3))][PF(6)] (3),
      and [(CQ)Au(PEt(3))][PF(6)] (4), respectively. KAuCl(4) reacted with CQ to
      produce the Au(III) complex [(CQ)(2)Au(Cl)(2)]Cl (5), which in turn formed
      [(CQ)Au(Cl)(SR)(Et(2)O)]Cl (6) by reaction with 1-thio-beta-d-glucose-2,3,4,6
      tetraacetate (SRH). The new compounds were characterized by a combination of
      elemental analysis, fast atom bombardment mass spectrometry (FAB-MS), and NMR
      spectroscopy. All the complexes display in vitro activity against CQ-sensitive
      and CQ-resistant strains of Plasmodium falciparum. The highest activity for this
      series was obtained for complex 4, which is 5 times more active than chloroquine
      diphosphate (CQDP) against the CQ-resistant strain FcB1. On preincubation of
      noninfected red blood cells with complexes 1, 5, and 6, protection against
      subsequent infection was observed in some cases. No clear structure-activity
      correlations could be established for this series of compounds.

PMID- 15456264
TI  - Novel cationic lipids incorporating an acid-sensitive acylhydrazone linker:
      synthesis and transfection properties.
AB  - Cationic lipid-mediated gene transfection involves uptake of the lipid/DNA
      complexes via endocytosis, a cellular pathway characterized by a significant drop
      in pH. Thus, in the present study, we aimed to explore the impact on transfection
      efficiency of the inclusion of an acid-sensitive acylhydrazone function in the
      cationic lipid structure. We synthesized and evaluated the transfection
      properties of a series of four cationic steroid derivatives characterized by an
      acylhydrazone linkage connecting a guanidinium-based headgroup to a saturated
      cholestanone or an unsaturated cholest-4-enone hydrophobic domain. Acid-catalyzed
      hydrolysis was confirmed for all lipids, its rate being highest for those with a
      cholestanone moiety. The compound bis-guanidinium bis(2-aminoethyl)amine
      hydrazone (BGBH)-cholest-4-enone was found to mediate efficient gene transfection
      into various mammalian cell lines in vitro and into the mouse airways in vivo. In
      vitro transfection studies with BGBH-cholest-4-enone formulations also showed
      that incorporation of a degradable acylhydrazone bond led to low cytotoxicity and
      impacted the intracellular trafficking of the lipoplexes. Thus, our work allowed
      us to identify a cationic lipid structure with an acid-cleavable acylhydrazone
      linker capable of mediating efficient gene transfection in vitro and in vivo and
      it thereby provides a basis for further development of related acid-sensitive
      gene delivery systems.

PMID- 15456265
TI  - Carbonic anhydrase inhibitors: the first on-resin screening of a 4
      sulfamoylphenylthiourea library.
AB  - Sulfonamide carbonic anhydrase (CA) inhibitors are widely employed in the
      diagnosis and treatment of diverse diseases such as glaucoma and different
      neuromuscular disorders. Moreover, an emerging area is represented by their use
      in the prevention and treatment of tumors. In this paper we propose an optimized
      synthesis of on-resin CA inhibitor libraries to be used for a high-throughput
      biological screening. A library of 4-sulfamoylphenylthioureas, previously
      described to be attractive candidates as novel antiglaucoma drugs, has been
      synthesized by a solid-phase approach, avoiding the formation of thiohydantoin
      side products. The on-resin screening assay has been developed for the inhibition
      tests of different CA isozymes with the on-resin supported sulfonamides, allowing
      the direct identification of the biologically active lead compounds. These
      results allow the development of new designed libraries in the solid phase of
      sulfonamide CA inhibitors characterized by a set of prefixed parameters to be
      used as possible drug candidates.

PMID- 15456266
TI  - Synthesis and potent antitumor activities of novel 1,3,5-cis,cis
      triaminocyclohexane N-pyridyl derivatives.
AB  - The iron chelator N,N',N' '-tris(2-pyridylmethyl)-cis,cis-1,3,5
      triaminocyclohexane (tachpyr) was recently reported to display potent antitumor
      activity. The present study was focused on identifying an adequate bifunctional
      version of tachpyr as a lead compound for use in antibody-targeted iron depletion
      tumor therapy. Preparation of tachpyr derivatives having a side chain is
      reported, and their cytotoxic activity is evaluated in the HeLa cell line. The
      observed cytotoxity appears dependent on the functionalization site of the
      tachpyr employed for introducing the protein conjugation. Tachpyr derivatives 14
      and 15 having a side chain introduced into the 5-position of the pyridyl ring
      display more potent cytotoxicity than tachpyr derivatives 7 and 8 having a side
      chain introduced onto one of the secondary amines. BOC-protected tachpyr
      derivative 14 exhibited the most potent cytotoxicity against this cancer cell
      line, which was reasonably comparable to the parent tachpyr. Tachpyr derivative
      14 was further converted into bifunctional tachpyr 17 possessing a maleimide
      linker for conjugation with thiolated monoclonal antibodies (mAbs).

PMID- 15456267
TI  - Subtype selective substrates for histone deacetylases.
AB  - To probe the steric requirements for deacylation, we synthesized lysine-derived
      small molecule substrates and examined structure-reactivity relationships with
      various histone deacetylases. Rat liver, human HeLa, and human recombinant class
      I and II histone deacetylases (HDACs) as well as human recombinant NAD(+)
      dependent SIRT1 (class III enzyme) were used in these studies. A
      benzyloxycarbonyl substituent on the alpha-amino group yielded the highest
      conversion rates. Replacing the epsilon-acetyl group with larger lipophilic acyl
      substituents led to a pronounced decrease in conversion by class I and II
      enzymes; the class III enzyme displayed a greater tolerance. Incubations with
      recombinant FLAG-tagged human HDACs 1, 3, and 6 showed a distinct subtype
      selectivity among small molecule substrates. The subtype selectivity of HDAC
      inhibitors could be predicted with these substrates and an easily obtainable
      mixture of HDAC subtypes.

PMID- 15456268
TI  - Rational design, synthesis, and biological evaluation of bis(pyrimido[5,6,1
      de]acridines) and bis(pyrazolo[3,4,5-kl]acridine-5-carboxamides) as new
      anticancer agents.
AB  - The good results obtained with pyrimido[5,6,1-de]acridines 7 and with
      pyrazolo[3,4,5-kl]acridinecarboxamides 8 prompted us to the synthesis of two new
      series of bis acridine derivatives: the bis(pyrimidoacridines) 5 and the
      bis(pyrazoloacridinecarboxamides) 6. Compounds 5 can be regarded also as cyclized
      derivatives of bis(acridine-4-carboxamides) 3 and compounds 6 as cyclized
      derivatives of bis(acridine-4-carboxamides) 4. The noncovalent DNA-binding
      properties of these compounds have been examined using fluorometric techniques.
      The results indicate that (i) the target compounds are excellent DNA ligands;
      (ii) the bis derivatives 5 and 6 are more DNA-affinic than corresponding monomers
      7 and 8; (iii) the new bis 5 and 6 result always less efficient in binding than
      related bis(acridine-4-carboxamides) 3 and 4; and (iv) in both series 5 and 6 a
      clear, remarkable in some cases, preference for binding to AT rich duplexes can
      be noted. In vitro cytotoxic potency of these derivatives toward the human colon
      adenocarcinoma cell line (HT29) is described and compared to that of reference
      drugs. Structure-activity relationships are discussed. We could identify six very
      potent cytotoxic compounds for further in vitro studies: a cytotoxic screening
      against six human cancer cell lines and the National Cancer Institute (NCI)
      screening on 60 human tumor cell lines. Finally, compound 6a was selected for
      evaluation in a NCI in vivo hollow fiber assay.

PMID- 15456269
TI  - Stereoselective synthesis of sugar-modified enyne analogues of adenosine and
      uridine. Interaction with S-adenosyl-L-homocysteine hydrolase and antiviral and
      cytotoxic effects.
AB  - Sonogashira coupling of (E)-6'-iodohomovinyl nucleosides 1 with
      (trimethylsilyl)acetylene gave the conjugated 8'-(trimethylsilyl)enyne
      derivatives of the adenosine 2a and uridine 2b with expected E-stereochemistry.
      Desilylation of 2a,b with tetrabutylammonium fluoride followed by treatment with
      N-iodosuccinimide/AgNO(3) afforded 8'-iodoenynes 4a,b. Analogous coupling of (Z)
      6'-iodohomovinyl nucleosides 7a,b produced (Z)-8'-(trimethylsilyl)enynes 8a,b,
      which were deprotected with aqueous trifluoroacetic acid to give the Z-enynes
      9a,b. Stereoselective coupling of the adenosine 4'-acetylenic 11 and ethyl (Z)-3
      bromoacrylate followed by deprotection gave the conjugated enyne system attached
      in the reverse orientation at C4' 13. Because of their diverse stereochemical
      attributes, deprotected enyne analogues 5a, 6a, 9a, and 13 derived from adenosine
      require a different vicinity for binding with S-adenosyl-l-homocysteine (AdoHcy)
      hydrolase and/or addition of enzyme-bound water across the conjugated enyne
      system. Enyne 5a and 8'-iodoenyne 6a produced time-dependent and concentration
      dependent inhibition of AdoHcy hydrolase (K(i), 0.55 and 118.5 microM,
      respectively). No reduction in NAD(+) content of the enzyme and no iodide ion
      released were observed upon incubation of 6a with the enzyme, while incubation of
      5a produced 30% reduction in the NAD(+) content of the enzyme. No specific
      antiviral activity was noted for 5a,b, 6a,b, 9a,b, and 13 against any of the
      viruses tested; the E-iodoenynes 6a and 6b inhibited HIV-1 virus (IC(50), 1.1 and
      1.8 microM; selectivity index, 7 and 3, respectively). The E-enyne 5a showed
      activity against cytomegalovirus at a concentration (EC(50), 30 microM) that was
      3- to 10-fold lower than the cytotoxic concentration.

PMID- 15456270
TI  - 2-(2-(dimethylaminomethyl)phenoxy)-5-iodophenylamine: an improved serotonin
      transporter imaging agent.
AB  - Imaging serotonin transporters (SERT) is an emerging research tool potentially
      useful to cast light on the mechanisms of drug action as well as to monitor the
      treatment of depressed patients. We have prepared two new derivatives of 3, 2-(2
      (dimethylaminomethyl)phenoxy)-5-iodophenylamine (4) and 2-(2
      (dimethylaminomethyl)benzyl)-5-iodophenylamine (5) (K(i) for SERT = 0.37 and 48.6
      nM, respectively). Both [(125)I]4 and [(125)I]5 displayed excellent brain uptakes
      in rats, and they showed a highest uptake in hypothalamus (between 60 and 240
      min), a region populated with the highest density of SERT. The specific uptake of
      [(125)I]4 in the hypothalamus resulted in a target to nontarget ratio
      ([hypothalamus-cerebellum]/cerebellum) of 4.3 at 2 h. Autoradiography of rat
      brain sections (ex vivo at 2 h) of [(125)I]4 showed an excellent regional
      distribution pattern consistent with known SERT localization. These data suggest
      that [(123)I]4 may be useful for imaging SERT binding sites in the brain by
      single photon emission computed tomography (SPECT).

PMID- 15456271
TI  - Synthesis of benzodithiol-2-yl-substituted nucleoside derivatives as lead
      compounds having anti-bovine viral diarrhea virus activity.
AB  - Nucleoside derivatives having a benzodithiol-2-yl (BDT) group were synthesized
      and examined for their anti-bovine viral diarrhea virus (BVDV) activities. Other
      substituents structurally similar to the BDT group such as 1,3-benzodioxol-2-yl,
      benzimidazol-2-yl and 1-oxo-benzodithiol-2-yl groups were not effective as the
      pharmacophore. The anti-BVDV assay revealed that 2'-O-BDT-guanosine and 2'-O-BDT
      inosine had the strongest anti-BVDV activity among the nucleoside derivatives
      synthesized in this study. Since BVDV has been recognized as a surrogate for
      human hepatitis C virus (HCV), the BDT-modified nucleosides might become a new
      class of lead compounds to find nucleoside-type anti-HCV agents such as
      ribavirin.

PMID- 15456272
TI  - Synthesis and evaluation of nitrofuranylamides as novel antituberculosis agents.
AB  - In an effort to develop new and more potent therapies to treat tuberculosis, a
      library of compounds was screened for M. tuberculosis UDP-Gal mutase inhibition.
      Nitrofuranylamide 1 was identified as a hit in this screen, possessing good
      antituberculosis activity. This paper describes the synthesis and evaluation of
      an expanded set of nitrofuranylamides. We have discovered a number of
      nitrofuranylamides with submicromolar M. tuberculosis MIC values and acceptable
      therapeutic indexes. The MIC activity did not correlate with UDP-Gal mutase
      inhibition, suggesting an alternative primary cellular target was responsible for
      the antituberculosis activity. The compounds were only active against
      mycobacteria of the tuberculosis complex. On the basis of these results, four
      compounds were selected for in vivo testing in a mouse model of tuberculosis
      infection, and of these compounds one showed significant antituberculosis
      activity.

PMID- 15456273
TI  - Structure-activity relationship of heterobase-modified 2'-C-methyl
      ribonucleosides as inhibitors of hepatitis C virus RNA replication.
AB  - Hepatitis C virus infection constitutes a significant health problem in need of
      more effective therapies. We have recently identified 2'-C-methyladenosine and 2'
      C-methylguanosine as potent nucleoside inhibitors of HCV RNA replication in
      vitro. However, both of these compounds suffered from significant limitations. 2'
      C-Methyladenosine was found to be susceptible to enzymatic conversions by
      adenosine deaminase and purine nucleoside phosphorylase, and it displayed limited
      oral bioavailability in the rat. 2'-C-Methylguanosine, on the other hand, was
      neither efficiently taken up in cells nor phosphorylated well. As part of an
      attempt to address these limitations, we now report upon the synthesis and
      evaluation of a series of heterobase-modified 2'-C-methyl ribonucleosides. The
      structure-activity relationship within this series of nucleosides reveals 4-amino
      7-(2-C-methyl-beta-d-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine and 4-amino-5
      fluoro-7-(2-C-methyl-beta-d-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine as potent
      and noncytotoxic inhibitors of HCV RNA replication. Both 4-amino-7-(2-C-methyl
      beta-d-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine and 4-amino-5-fluoro-7-(2-C
      methyl-beta-d-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine display improved
      enzymatic stability profiles as compared to that of 2'-C-methyladenosine.
      Consistent with these observations, the most potent compound, 4-amino-5-fluoro-7H
      pyrrolo[2,3-d]pyrimidine ribonucleoside, is orally bioavailable in the rat.
      Together, the potency of the 2'-C-methyl-4-amino-pyrrolo[2,3-d]pyrimidine
      ribonucleosides and their improved pharmacokinetic properties relative to that of
      2'-C-methyladenosine suggests that this class of compounds may have clinical
      utility.

PMID- 15456274
TI  - Design and synthesis of novel indole beta-diketo acid derivatives as HIV-1
      integrase inhibitors.
AB  - Diketo acids such as S-1360 (1A) and L-731,988 (2) are potent and selective
      inhibitors of HIV-1 integrase (IN). A plethora of diketo acid-containing
      compounds have been claimed in patent literature without disclosing much
      biological activities and synthetic details (reviewed in Neamati, N. Exp. Opin.
      Ther. Pat. 2002, 12, 709-724). To establish a coherent structure-activity
      relationship among the substituted indole nucleus bearing a beta-diketo acid
      moiety, a series of substituted indole-beta-diketo acids (4a-f and 5a-e) were
      synthesized. All compounds tested showed anti-IN activity at low micromolar
      concentrations with varied selectivity against the strand transfer process. Three
      compounds, the indole-3-beta-diketo acids 5a and 5c, and the parent ester 9c,
      have shown an antiviral activity in cell-based assays. We further confirmed a
      keto-enolic structure in the 2,3-position of the diketo acid moiety of a
      representative compound (4c) using NMR and X-ray crystallographic analysis. Using
      this structure as a lead for all of our computational studies, we found that the
      title compounds extensively interact with the essential amino acids on the active
      site of IN.

PMID- 15456275
TI  - Rapid prediction of chemical metabolism by human UDP-glucuronosyltransferase
      isoforms using quantum chemical descriptors derived with the electronegativity
      equalization method.
AB  - This study aimed to evaluate in silico models based on quantum chemical (QC)
      descriptors derived using the electronegativity equalization method (EEM) and to
      assess the use of QC properties to predict chemical metabolism by human UDP
      glucuronosyltransferase (UGT) isoforms. Various EEM-derived QC molecular
      descriptors were calculated for known UGT substrates and nonsubstrates.
      Classification models were developed using support vector machine and partial
      least squares discriminant analysis. In general, the most predictive models were
      generated with the support vector machine. Combining QC and 2D descriptors (from
      previous work) using a consensus approach resulted in a statistically significant
      improvement in predictivity (to 84%) over both the QC and 2D models and the other
      methods of combining the descriptors. EEM-derived QC descriptors were shown to be
      both highly predictive and computationally efficient. It is likely that EEM
      derived QC properties will be generally useful for predicting ADMET and
      physicochemical properties during drug discovery.

PMID- 15456276
TI  - 5-(tryptophylamino)-1,3-dioxoperhydropyrido[1,2-c]pyrimidine-based
      cholecystokinin receptor antagonists: reversal of CCK1 receptor subtype
      selectivity toward CCK2 receptors.
AB  - With the aim of reversing selectivity or antagonist/agonist functionality in the
      5-(tryptophylamino)-1,3-dioxoperhydropyrido[1,2-c]pyrimidine-derived potent and
      highly selective CCK(1) antagonists, a series of 4-benzyl and 4-methyl
      derivatives have been synthesized. Whereas the introduction of the benzyl group
      led, in all cases, to complete loss of the binding affinity, the incorporation of
      the methyl group gave a different result depending on the stereochemistry of the
      1,3-dioxoperhydropyrido[1,2-c]pyrimidine scaffold. Thus, the introduction of the
      methyl group into the (4aS,5R)-diastereoisomers, giving a (4S)-configuration,
      produced a 3-fold increase in the CCK(1) binding potency and selectivity.
      However, the same structural manipulation in the opposite (4aR,5S)
      stereochemistry, leading to a (4R,4aR,5S)-configuration, produced reversal of the
      selectivity for CCK(1) to the CCK(2) receptors. The replacement of the Boc group
      at the tryptophan moiety by a 2-adamantyloxycarbonyl group also contributed to
      that reversal. The resulting compounds displayed moderate CCK(2) antagonist
      activity in rat and human receptors, and a very small partial agonist effect on
      the production of inositol phosphate in COS-7 cells transfected with the wild
      type human CCK(2) receptor.

PMID- 15456277
TI  - Ultrasensitive detection of protein using an aptamer-based exonuclease protection
      assay.
AB  - Currently, methods for protein detection are not as sensitive and specific as
      methods for detection of specific nucleic acid sequences. Here, we present an
      analogous technique for detection of proteins using aptamers as ligands for
      target binding. We have named this method the aptamer-based exonuclease
      protection assay. We applied a special oligonucleotide probe containing a
      thrombin aptamer, which has the capacity to recognize thrombin with high affinity
      and specificity. The aptamer probe is a 22-base-long single-strand
      oligonucleotide with the thrombin aptamer sequence at the 3'-terminus and 7
      additional nucleotides at the 5'-terminus, which is able to bind thrombin with
      high affinity and specificity. In the exonuclease protection assay, thrombin
      binds the aptamer and thereby protects it from degradation by exonuclease I,
      whereas any unbound aptamer probe is degraded by exonuclease I. Subsequently, the
      aptamer probes that were protected from exonuclease I by thrombin act as linkers
      to join two free connectors, which contain sequences matching the probe. The
      joined products, which reflect the identity and amount of the target protein, are
      amplified by PCR. The exonuclease protection assay is extremely sensitive, since
      it is based on PCR amplification. This method can detect as few as several
      hundred molecules of target protein without using washes or separations. In
      addition, this new method for protein detection is simple and inherits all the
      advantages of aptamers. The mechanism, moreover, may be generalized and used for
      other forms of protein analysis.

PMID- 15456278
TI  - Electron hopping dynamics in monolayer-protected au cluster network polymer films
      by rotated disk electrode voltammetry.
AB  - Electrons are transported within polymeric films of alkanethiolate monolayer
      protected Au clusters (MPCs) by electron hopping (self-exchange) between the
      metal cores. The surrounding monolayers, the molecular linkers that generate the
      network polymer film, or both, presumably serve as tunneling bridges in the
      electron transfers. This paper introduces a steady-state electrochemical method
      for measuring electron hopping rates in solvent-wetted and swollen, ionically
      conductive MPC films. The films are network polymer films of nanoparticles,
      coated on a rotated disk electrode that is contacted by a solution of a redox
      species (decamethylferrocene, CpFe). Controlling the electrode potential such
      that the film mediates oxidation of the redox probe can force control of the
      overall current onto the rate of electron hopping within the film, which is
      characterized as the apparent electron diffusion coefficient D(E). D(E) is
      translated into an apparent electron hopping rate k(ET) by a cubic lattice model.
      The experiment is applied to MPC network polymer films linked by alpha,omega
      alkanedithiolates and by metal ion-carboxylate connections. We evaluate the
      dependencies of apparent hopping rate on CpFe concentration, film thickness,
      electrode potential relative to the CpFe formal potential, film-swelling solvent,
      and temperature. The apparent hopping rates are in the 10(4)-10(5) s(-)(1) range,
      which is slower than those for the same kind of MPC films, but in a dry
      (nonswollen) state measured by electronic conductivities.

PMID- 15456279
TI  - General strategy for biosensor design and construction employing multifunctional
      surface-tethered components.
AB  - Biosensors function by reversibly linking bioreceptor-target analyte binding with
      closely integrated signal generation and can either continuously monitor analyte
      concentrations or be returned to baseline readout values by removal of analyte.
      We present an approach for producing fully reversible, reagentless, self
      assembling biosensors on surfaces. In the prototype biosensor, quencher-dye
      labeled biotin-linked E. coli maltose binding protein (MBP) bound in a specific
      orientation to a NeutrAvidin-coated surface is employed as a bioreceptor. To
      complete sensor formation, a modular tether arm consisting of a flexible
      biotinylated DNA oligonucleotide, a fluorescence resonance energy-transfer (FRET)
      donor dye, and a distal beta-cyclodextrin (beta-CD) analyte analogue is bound in
      an equimolar amount to the same surface by means of DNA-directed immobilization.
      After self-assembly, a baseline level of FRET quenching is observed due to
      specific interaction between the beta-CD of the flexible tether arm and the sugar
      binding site of MBP, which brings the two dyes into proximity. Addition of the
      target analyte, the nutrient maltose, displaces the linked beta-CD-dye of the DNA
      based tether arm, and a concentration-dependent change in FRET results. Biosensor
      sensitivity and dynamic range can be controlled by either using MBP variants
      having different binding constants or by binding of modulator DNA
      oligonucleotides that are complementary to the flexible DNA tether. The sensor
      can be regenerated and returned to baseline quenching levels by washing away
      analyte. A complex set of interactions apparently exists on the sensing surface
      that may contribute to sensor behavior and range. This approach may represent a
      general way to assemble a wide range of useful biosensors.

PMID- 15456280
TI  - In situ tissue analysis of neuropeptides by MALDI FTMS in-cell accumulation.
AB  - Herein we report the first application of Fourier transform mass spectrometry for
      the analysis of neuropeptides directly from neuronal tissues. Sample preparation
      protocols and instrumentation conditions are developed to allow in situ
      neuropeptide analysis of the neuroendocrine organs freshly isolated from a marine
      organism Cancer borealis. The utility of a previously developed in-cell
      accumulation (ICA) technique is extended for peptide analysis in complex tissue
      samples. With the ICA procedure, ion signals from multiple laser shots are
      accumulated in the analyzer cell prior to detection. This procedure allows the
      accumulation of ion signals without accumulating noise, thus improving the signal
      to-noise ratio and enhancing the sensitivity for the detection of trace-level
      endogenous neuropeptides. De novo sequencing of peptides directly from tissue
      samples becomes more feasible through this improvement. Additionally, an
      integrated pulse sequence is constructed to cover a wide mass range from m/z 215
      to 9000 by centering quadrupole collection of ions at different masses for
      successive laser shots. Finally, improved mass measurement accuracy (2 ppm) for
      tissue peptide analysis is achieved using ICA by incorporating calibrants on a
      separate spot from the sample of interest without premixing calibration standards
      with the analytes.

PMID- 15456281
TI  - Electric field gradient focusing of proteins based on shaped ionically conductive
      acrylic polymer.
AB  - Electric field gradient focusing (EFGF) is a separation technique that uses an
      electric field gradient and an opposing hydrodynamic flow to separate and
      concentrate charged analytes. This work describes miniaturized EFGF devices that
      are used for protein analysis. These devices employ a unique ionically conductive
      polymer that enables the required electric field gradient to be established. This
      polymer has good protein compatibility and allows the transport of small buffer
      ions while retaining large analytes such as proteins. With the use of an EFGF
      device, green fluorescent protein was concentrated 10 000-fold and the separation
      of a protein mixture was demonstrated. The development of these ionically
      conductive polymer-based devices represents a step toward making EFGF a useful
      analytical tool for proteomics investigations.

PMID- 15456282
TI  - Disposable noncompetitive immunosensor for free and total prostate-specific
      antigen based on capacitance measurement.
AB  - This work reports on the successful integration of a one-step lateral flow
      immunoassay format and impedance detection of the specific affinity event using
      an electrochemical transducer coated with a pH-sensitive polymer layer. This
      approach was particularly applied to the development of a rapid single-use
      immunosensor for the sensitive detection of free and total prostate-specific
      antigen (f-PSA, t-PSA) tumor marker. Strips of nitrocellulose membrane were
      coated with appropriate antibodies to f-PSA and t-PSA and used as solid supports
      for the performance of noncompetitive immunoassays where PSA was allowed to react
      with both immobilized anti-PSA antibody and anti-PSA urease enzyme conjugate for
      less than 1 min. An additional piece within the device consisting of a storage
      blister filled with a urea solution allowed the rapid washing of unbound species
      from the membrane strips and simultaneous urea hydrolysis catalyzed by the bound
      urease conjugate in an automatic fashion. The hydrolysis of urea increased the pH
      of the reaction media, which in turn induced a breakdown of the polymer layer on
      the transducer and a consequent measurable change in capacitance of the system.
      This was easily recorded at a given frequency over a 30-min period. Overall, we
      describe a one-step immunosensor prototype that exhibits enough sensitivity to
      detect both forms of PSA at concentration levels down to 3 ng/mL. With the
      possibility of being portable and considering its ease of use, robustness, and
      simplicity, this device has great potential as a tool for the screening and early
      detection of prostate cancer.

PMID- 15456283
TI  - Second-order advantage achieved with four-way fluorescence excitation-emission
      kinetic data processed by parallel factor analysis and trilinear least-squares.
      Determination of methotrexate and leucovorin in human urine.
AB  - Four-way fluorescence data recorded by following the kinetic evolution of
      excitation-emission fluorescence matrices (EEMs) have been analyzed by parallel
      factor analysis and trilinear least-squares algorithms. These methodologies
      exploit the second-order advantage of the studied data, allowing analyte
      concentrations to be estimated even in the presence of an uncalibrated
      fluorescent background. They were applied to the simultaneous determination of
      the components of the anticancer combination of methotrexate and leucovorin in
      human urine samples. Both analytes were converted into highly fluorescent
      compounds by oxidation with potassium permanganate, and the kinetics of the
      reaction was continuously monitored by recording full EEM of the samples at
      different reaction times. A commercial fast scanning spectrofluorometer has been
      used for the first time to measure the four-way EEM kinetic data. The rapid
      scanning instrument allows the acquisition of a complete EEM in 12 s at a
      wavelength scanning speed of 24 000 nm/min. The emission spectra were recorded
      from 335 to 490 nm at 5-nm intervals, exciting from 255 to 315 nm at 6-nm
      intervals. Ten successive EEMs were measured at 72-s intervals, to follow the
      fluorescence kinetic evolution of the mixture components. Good recoveries were
      obtained in synthetic binary samples and also in spiked urine samples. The
      excitation, emission, and kinetic time profiles recovered by both chemometric
      techniques are in good agreement with experimental observations.

PMID- 15456284
TI  - Mass spectrometry of UV-cross-linked protein-nucleic acid complexes:
      identification of amino acid residues in the single-stranded DNA-binding domain
      of human replication protein A.
AB  - Photochemical cross-linking of human replication protein A (hRPA) to
      oligonucleotide dT30 was performed to enable identification of amino acid
      sequences that reside in the DNA-binding domain. A nucleoprotein complex, with a
      1:1 protein/DNA stoichiometry, was separated from unreacted enzyme and
      oligonucleotide by SDS-polyacrylamide gel electrophoresis and subjected to in-gel
      digestion with trypsin. Three cross-linked tryptic peptides (nucleopeptides) of
      hRPA70xdT30 (T43, T28/29, and a truncated T24/25) were isolated. Combined mass
      spectrometric and C-terminal proteolysis experiments showed that at least one
      amino acid in the segment 235-ATAFNE-240 (located in T24/25), at least one out of
      the two residues sequence 269-FT-270 (located in T28/29), and at least one from
      the sequence 383-VSDF-386 (located in T43) were involved in cross-linking. These
      peptides contained aromatic residues (F238, F269, and F386 respectively) that can
      form base-stacking interactions with the DNA and were, therefore, most likely to
      be involved in cross-linking. The results obtained in this study demonstrate that
      a combination of exhaustive proteolysis and MALDI TOF MS can localize the sites
      of DNA binding to very short sequences of amino acids. Data so acquired can
      confirm or amend information obtained from site-directed mutagenesis and X-ray
      crystallography.

PMID- 15456285
TI  - Real-time surface plasmon resonance imaging measurements for the multiplexed
      determination of protein adsorption/desorption kinetics and surface enzymatic
      reactions on peptide microarrays.
AB  - The kinetics of protein adsorption/desorption onto peptide microarrays was
      studied using real-time surface plasmon resonance (SPR) imaging. S protein
      binding interactions were examined using an array composed of five different
      peptides: N terminal and C terminal immobilized wild-type S peptide (S1 and S2),
      an alternate binding sequence derived by phage display (LB2), an NVOC-protected S
      peptide, and a FLAG peptide control sequence (F). Kinetic measurements of the S
      protein-S1 peptide interaction were analyzed to determine a desorption rate
      constant (k(d)) of 1.1 (+/-0.08) x 10(-2) s(-1), an adsorption rate constant
      (k(a)) of 1.9 (+/-0.05) x 10(5) M(-1) s(-1), and an equilibrium adsorption
      constant (K(Ads)) of 1.7 (+/-0.08) x 10(7) M(-1). SPR imaging equilibrium
      measurements of S protein to S1 peptide were performed to independently confirm
      the kinetically determined value of K(Ads). Rate constants for the S2 and LB2
      peptides on the array were measured as follows: 1.6 (+/-0.04) x 10(5) M(-1) s(-1)
      (k(a)) and 1.1 (+/-0.07) x 10(-2) s(-1) (k(d)) for S2, 1.2 (+/-0.05) x 10(5) M(
      1) s(-1) (k(a)) and 1.1 (+/-0.03) x 10(-2) s(-1) (k(d)) for LB2. In addition to S
      protein adsorption/desorption, real-time SPR imaging of peptide arrays was
      applied to study the surface enzymatic activities of the protease factor Xa.
      Enzymatic cleavage of the substrate peptide (P1) was shown to follow first-order
      kinetics and proceed at a rate 10 times faster than that of the mutant peptide
      (P2), with cleavage velocities of 5.6 (+/-0.3) x 10(-4) s(-1) for P1 and 5.7 (+/
      0.3) x 10(-5) s(-1) for P2.

PMID- 15456286
TI  - Impact of nano- and mesoscale particles on the performance of microcantilever
      based sensors.
AB  - Microcantilever-based sensors comprise an emerging class of chemomechanical
      sensors. The crucial challenge for every new and promising sensing platform lies
      in its performance in complex mixtures. Since most biofluids are rich in
      particulates, we assessed the impact of particles in the liquid stream on the
      performance of microcantilever sensors operated in both deflection and resonance
      modes. For both detection modes, sensor response depends on the particle
      diameter, concentration, and velocity as well as the composition of a thin-film
      coating. The presence of particles in the fluid stream produce substantial
      scattering of the laser beam used to measure cantilever deflection. Thus, prior
      removal of particulate matter from biofluids is required for optimal performance
      of microcantilever-based biosensors.

PMID- 15456287
TI  - Electrocatalytic oxidation of guanine and DNA on a carbon paste electrode
      modified by cobalt hexacyanoferrate films.
AB  - The electrochemical behavior of cobalt hexacyanoferrate complex adsorbed on a
      carbon paste electrode (CPE) and its application to the electrocatalytic
      oxidation of guanine and single-strand DNA (ss-DNA) in aqueous solution are
      investigated in this report. The modification of CPE by the adsorption of this
      complex results in excellent amplification of the guanine oxidation response of
      ss-DNA. The effects of paste composition, scan rate, DNA, and guanine
      concentration were studied. The detection limits of 52 and 920 ng mL(-)(1) were
      obtained for guanine and ss-DNA, respectively.

PMID- 15456288
TI  - Resolving neurotransmitters detected by fast-scan cyclic voltammetry.
AB  - Carbon-fiber microelectrodes are frequently used as chemical sensors in
      biological preparations. In this work, we evaluated the ability of cyclic
      voltammograms recorded at fast-scan rates to resolve neurochemicals when analyzed
      by principal component regression. A calibration set of 30 cyclic voltammograms
      was constructed from 9 different substances at a variety of concentrations. The
      set was reduced by principal component analysis, and it was found that 99.5% of
      the variance in the data could be captured with five principal components. This
      set was used to evaluate cyclic voltammograms obtained with one or two compounds
      present in solution. In most cases, satisfactory predictions of the identity and
      concentration of analytes were obtained. Chemical dynamics were also resolved
      from a set of fast-scan cyclic voltammograms obtained with the electrode
      implanted in a region of a brain slice that contains dopaminergic terminals.
      Following stimulation, principal component regression of the data resolved the
      changes in dopamine and pH that were evoked. In a second test of the method,
      vesicular release was measured from adrenal medullary cells and the data were
      evaluated with a calibration set composed of epinephrine and norepinephrine.
      Cells that secreted one or the other were identified. Overall, the results show
      that principal component regression with appropriate calibration data allows
      resolution of substances that give overlapping cyclic voltammograms.

PMID- 15456289
TI  - A microfabricated device for subcellular organelle sorting.
AB  - We report a microfabricated field flow fractionation device for continuous
      separation of subcellular organelles by isoelectric focusing. The microdevice
      provides fast separation in very small samples while avoiding large voltages and
      heating effects typically associated with conventional electrophoresis-based
      devices. The basis of the separation is the presence of membrane proteins that
      give rise to the effective isoelectric points of the organelles. Simulations of
      isoelectric focusing of mitochondria in microchannels are used to assess design
      parameters, such as dimensions and time scales. In addition, a model of Joule
      heating effects in the microdevice during operation indicates that there is no
      significant heating, even without active cooling. The device is fabricated using
      a combination of photolithography, thin-film metal deposition/patterning, and
      electroplating techniques. We demonstrate that in the microfluidic devices,
      mitochondria from cultured cells migrate under the influence of an electric field
      into a focused band in less than 6 min, consistent with model predictions. We
      also illustrate separation of mitochondria from whole cells and nuclei as well as
      the separation of two mitochondrial subpopulations. When automated and operated
      in parallel, these microdevices should facilitate high-throughput analysis in
      studies requiring separation of organelles.

PMID- 15456290
TI  - Antibody arrays prepared by cutinase-mediated immobilization on self-assembled
      monolayers.
AB  - Antibody arrays hold considerable potential in a variety of applications
      including proteomics research, drug discovery, and diagnostics. Many of the
      schemes used to fabricate the arrays fail to immobilize the antibodies at a
      uniform density or in a single orientation; consequently, the immobilized
      antibodies recognize their antigens with variable efficiency. This paper
      describes a strategy to immobilize antibodies in a single orientation, with a
      controlled density, using the covalent interaction between cutinase and its
      suicide substrate. Protein fusions between cutinase and five antibodies of three
      different types (scFv, V(HH), and FN3) were prepared and immobilized upon self
      assembled monolayers (SAMs) presenting a phosphonate capture ligand. The
      immobilized antibodies exhibit high affinity and selectivity for their target
      antigens, as monitored by surface plasmon resonance and fluorescence scanning.
      Furthermore, by changing the density of capture ligand on the SAM the density of
      the immobilized antibody could be controlled. The monolayers, which also present
      a tri(ethylene glycol) group, are inert to nonspecific adsorption of proteins and
      allow the detection of a specific antigen in a complex mixture. The demonstration
      of cutinase-directed antibody immobilization with insert SAMs provides a
      straightforward and robust method for preparing antibody chips.

PMID- 15456291
TI  - Monitoring molecular beacon/DNA interactions using atomic force microscopy.
AB  - The molecular beacon (MB) is a new fluorescence probe containing a single
      stranded oligonucleotide with a probe sequence embedded in complementary
      sequences that form a hairpin stem. Due to the inherent fluorescent signal
      transduction mechanism, an MB functions as a sensitive probe with a high signal
      to-background ratio for real-time monitoring and provides a variety of exciting
      opportunities in DNA, RNA, and protein studies. To better understand the
      properties of MBs, the specific interactions between MB and target DNA
      (complementary and one-base mismatch) have been directly investigated by atomic
      force microscopy. The interaction force between a linear DNA probe and the target
      DNA was also detected and compared to that between MB and target DNA. The results
      demonstrate the high specificity of the MB/target DNA compared to the linear
      DNA/target DNA interaction.

PMID- 15456292
TI  - Quantification of ternary mixtures of heavy metal cations from metallochromic
      absorbance spectra using neural network inversion.
AB  - A new method based on artificial neural networks (ANN) for the processing of
      spectrophotometric data is proposed and illustrated on the example of the
      simultaneous quantification of ternary mixtures of zinc, cadmium, and mercury
      cations in aqueous solutions. Three types of commercially available
      metallochromic indicators were used as a simple model setup to create spectral
      data analogous to those normally received from an optical sensor array. In
      conventional ANN training methods for chemical sensors based on
      spectrophotometric data, a calibration is established by mathematically
      correlating the measured optical signal as network input with the concentration
      of the calibration sample as network output. In several situations, however,
      especially when dealing with mixed sample solutions, the relationship between a
      measured absorption spectrum and the corresponding ion concentrations is
      ambiguous, resulting in an "ill-posed problem". On the other hand, if the
      training direction is reversed by correlating known sample concentrations with
      measured optical signals, the relationship becomes reasonable for the ANN to
      obtain its structure. The proposed model illustrated in this paper is based on a
      more reasonable direct mapping and estimation by artificial neural network
      inversion (ANNI). In the training step, sample mixtures of known concentrations
      are optically measured to construct networks correlating the input data (ion
      concentrations) and the output data (absorption spectra). In the estimation step,
      the ion concentrations of unknown samples are estimated using the constructed
      ANN. The measured spectra of the unknown samples are fed to the output layer, and
      the appropriate input concentrations are determined by ANNI. When training the
      ANN system with 143 ternary mixtures of Zn2+, Cd2+, and Hg2+ in a concentration
      range from 1 to 100 microM, root-mean-square errors of prediction (RMSEP) of 0.45
      (Zn2+), 0.96 (Cd2+), and 0.32 microM (Hg2+) were observed for the estimation of
      concentrations in 30 test samples, using the ANNI procedure. This newly proposed
      model, which involves the construction of an ANN based on direct mapping and
      estimation by ANNI, opens up one way to overcome the limitations of nonselective
      sensors, allowing the use of more easily accessible semiselective receptors to
      realize smart chemical sensing systems.

PMID- 15456293
TI  - Quantitative 13C NMR analysis of sequence distributions in poly(ethylene-co-1
      hexene).
AB  - Different 13C NMR methods of determining triad distributions in two poly(ethylene
      co-1-hexene) copolymers are examined using high signal-to-noise ratio 13C NMR
      spectra of the copolymers dissolved in deuterated 1,2,4-trichlorobenzene at 398
      K. This examination includes a comparison of three integration techniques. The
      experimental impact of decoupler sidebands and significantly nonequal 13C NOE
      values are examined. A least-squares regression analysis technique for solving
      for triad mole fractions is tested and appears to be more reliable than two
      published algebraic expressions (and other expressions examined in the work
      reported here). The resultant triad mole fractions are compared to sequence
      distribution parameters expected by Bernoullian and first-order Markovian
      statistical models. On the basis of 13C NMR-determined average reactivity ratios,
      the copolymer designated sample B (5.3 mol % 1-hexene) appears to be a
      Bernoullian copolymer resulting from a single-site catalytic system. The
      copolymer designated sample S (3.6 mol % 1-hexene overall) is better described as
      a mixture of polyethylene and a Bernoullian copolymer with 6.4 mol % 1-hexene
      content, and thus appears to result from a multisite catalytic system.

PMID- 15456294
TI  - Glucose-sensitive holographic sensors for monitoring bacterial growth.
AB  - A glucose sensor comprising a reflection hologram incorporated into a thin,
      acrylamide hydrogel film bearing the cis-diol binding ligand, 3
      acrylamidophenylboronic acid (3-APB), is described. The diffraction wavelength
      (color) of the hologram changes as the polymer swells upon binding cis-diols. The
      effect of various concentrations of glucose, a variety of mono- and
      disaccharides, and the alpha-hydroxy acid, lactate, on the holographic response
      was investigated. The sensor displayed reversible changes in diffraction
      wavelength as a function of cis-diol concentration, with the sensitivity of the
      system being dependent on the cis-diol tested. The effect of varying 3-APB
      concentration in the hydrogel on the holographic response to glucose was
      investigated, and maximum sensitivity was observed at a functional monomer
      concentration of 20 mol %. The potential for using this holographic sensor to
      detect real-time changes in bacterial cell metabolism was demonstrated by
      monitoring the germination and subsequent vegetative growth of Bacillus subtilis
      spores.

PMID- 15456295
TI  - Broadband phase correction of FT-ICR mass spectra via simultaneous excitation and
      detection.
AB  - In typical Fourier transform ion cyclotron resonance (FT-ICR) mass spectra,
      temporally dispersed excitation and the delay between excitation and detection
      result in continuous variation of signal phase with frequency in the detected
      time-domain ion signal. The complex frequency-domain spectrum of such a signal is
      a linear combination of absorption- and dispersion-mode spectral components with
      corresponding asymmetric peaks. For this reason, magnitude-mode spectral display
      is usually employed to yield a phase-independent uniform and symmetrical peak
      shape at the expense of spectral resolution. In this work, we implement
      simultaneous excitation and detection to enable Fourier deconvolution to recover
      absorption-mode spectra for both low- and high-field FT-ICR instruments. These
      spectra yield resolving power improvement factors approaching the maximum
      theoretical limit of 2.0, as well as reduction in frequency assignment errors
      relative to conventional magnitude-mode spectra. The Fourier deconvolution
      procedure has the additional benefit of correcting for spectral variation
      resulting from nonuniform power distribution over the excitation bandwidth and
      the potential benefit of providing useful diagnostic information for
      interpretation of experimental performance.

PMID- 15456296
TI  - Determination of stable carbon isotopic compositions of low molecular weight
      dicarboxylic acids and ketocarboxylic acids in atmospheric aerosol and snow
      samples.
AB  - We report a new method developed for the determination of stable carbon isotopic
      composition of homologous alpha,omega-dicarboxylic acids and phthalic acid
      isolated from environmental samples such as atmospheric aerosols and snow.
      Dicarboxylic acids are derivatized with BF3/1-butanol to dibutyl esters, which
      are analyzed for the stable carbon isotopic composition using a capillary GC
      interfaced to on-line combustion isotope ratio mass spectrometer. The delta13C
      values for individual dicarboxylic acid are then calculated from delta13C of 1
      butanol and butyl ester derivative using a mass balance equation. The accuracy of
      the delta13C measurement for C2-C10 diacids is within 0.8 per thousand. We report
      a few examples of the delta13C ratios of saturated C2-C9 alpha,omega-dicarboxylic
      acids, unsaturated (maleic, phthalic) diacids, and oxocarboxylic acids in the
      aerosol and snow samples.

PMID- 15456297
TI  - Proteomic profiling of intact mycobacteria by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry.
AB  - Current methods for the identification of mycobacteria in culture are time
      consuming, requiring as long as 12 weeks for positive identification. One
      potential approach to rapid mycobacterial identification is to utilize proteomic
      profiling of cultures by matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry (MALDI-TOF MS). In this report, we have applied MALDI
      TOF MS to proteomic profiling of cultured microorganisms representing six species
      of the genus Mycobacterium. We find that analysis of acetonitrile/trifluoroacetic
      acid cellular extracts produces data similar to that of the analysis of deposited
      whole cells, while minimizing human contact with the microorganisms and rendering
      them nonviable. A matrix composition of alpha-cyano-4-hydroxycinnamic acid with
      fructose yields highly reproducible MALDI-TOF spectra. Statistical analysis of
      MALDI-TOF MS data allows differentiation of each individual mycobacterial species
      on the basis of unique mass fingerprints. The methodology allows identification
      of a number of unique (potentially diagnostic) biomarkers as targets for protein
      identification by MS/MS experiments. In addition, we observe a number of signals
      common to all mycobacterial species studied by MALDI-TOF MS, which may be genus
      specific biomarkers. The potentially genus-specific biomarkers occur at low mass
      (<2 kDa) and are likely to be lipids and cell wall components such as mycolic
      acids. This study demonstrates the potential for mass spectrometry-based
      identification/classification of mycobacteria.

PMID- 15456298
TI  - In-depth characterization of slurry packed capillary columns with 1.0-microm
      nonporous particles using reversed-phase isocratic ultrahigh-pressure liquid
      chromatography.
AB  - Fused-silica capillary columns packed with 1.0-microm nonporous C18 bonded
      particles are evaluated with isocratic ultrahigh-pressure liquid chromatography
      (UHPLC). Improved UHPLC techniques have demonstrated column efficiencies as high
      as 730 000 plates/m and run pressures over 6800 bar (100 000 psi) for packed 10
      microm-inner diameter (i.d.) columns. Columns as large as 150 microm have been
      tested with UHPLC and show no flow-induced heating effects on separation
      efficiencies. van Deemter plot analysis for column i.d.s ranging from 10 to 150
      microm shows an increase in column efficiency with a decrease in column i.d.
      Reduced parameter analysis further illustrates a decrease in reduced parameter A
      term and C term values with decreasing i.d. However, reduced parameter C term
      values for columns evaluated with UHPLC are an order of magnitude larger than C
      term values for larger particles at conventional pressures. Retention factors for
      moderately retained compounds are observed to increase with column i.d.,
      suggesting an increase in packing density. Highly ordered packing arrangement at
      the column wall is seen for packed beds extruded from large-diameter columns.

PMID- 15456299
TI  - Influence of operating parameters on the retention of chromatographic particles
      by thermal field-flow fractionation.
AB  - We have investigated the retention behavior of chromatographic particles in
      thermal field-flow fractionation (FFF). Retention time is found to increase with
      increasing temperature drop across the channel thickness, as expected for species
      exhibiting a thermophoretic mobility. Experiments have been performed with a
      vertically oriented channel rather than by using the classical horizontal
      configuration as this leads to much more reproducible retention data. In
      acetonitrile, silica-based particles are more retained than octadecyl-bonded
      silica particles, which confirms our previous finding, by means of a different
      method, that the thermophoretic mobility of the latter is smaller than that of
      the former. Whatever the type of particles and the nature of the carrier liquid,
      the relative retention time is observed to decrease with increasing carrier flow
      rate. This indicates that a hydrodynamic lift force acts on particles to move
      them away from the accumulation wall, as is usually observed in all FFF
      experiments with micrometer-sized particles. However, upward and downward flow
      directions in the vertical channel lead to similar retention data, indicating
      that inertial lift forces have a minor influence on retention. In addition, the
      relative retention time steadily decreases with increasing sample concentration,
      suggesting that the hydrodynamic lift force increases significantly with sample
      concentration. Accordingly, we speculate that a new transport phenomenon, called
      shear-induced hydrodynamic diffusion, not previously accounted for in the
      modeling of retention in FFF, is controlling the migration of the particles in
      the FFF channel. Implications of the influence of this phenomenon in other FFF
      experiments are discussed.

PMID- 15456300
TI  - Benzoyl derivatization as a method to improve retention of hydrophilic peptides
      in tryptic peptide mapping.
AB  - This study exploits the increase in chromatographic retention that accrues from
      benzoyl derivatization of primary amines as a tool to increase sequence coverage
      in tryptic peptide mapping. N-hydroxysuccinamide sulfonyl benzoate quantitatively
      derivatizes primary amines of peptides. Introduction of the hydrophobic benzoyl
      moiety into peptides increased retention of peptides during reversed-phase
      chromatography (RPC), particularly in the case of smaller hydrophilic peptides.
      Short chain (1-6 amino acids) tryptic fragments of model proteins lysozyme,
      myoglobin, and cytochrome c derivatized with N-hydroxysuccinamide sulfonyl
      benzoate eluted in the linear acetonitrile gradient. Application of benzoyl
      derivatization was further extended to achieve complete sequence coverage of a
      therapeutic protein, recombinant human growth hormone, and in detection of single
      amino acid polymorphism.

PMID- 15456301
TI  - Kinetics and the on-site application of standards in a solid-phase
      microextraction fiber.
AB  - The kinetics of the desorption of analytes from a SPME fiber into an agitated
      sample matrix was studied, and a theoretical model was proposed to describe the
      dynamic desorption process, based on the steady-state diffusion of analytes in
      the extraction phase and in the boundary layer. It was found that the desorption
      of analytes from a SPME fiber into an agitated sampling matrix is isotropic to
      the absorption of the analytes onto the SPME fiber from the sample matrix under
      the same agitation conditions, and this allows for the calibration of absorption
      using desorption. The calibration was accomplished by exposing a SPME fiber,
      preloaded with a standard, to an agitated sample matrix, during which desorption
      of the standard and absorption of analytes occurred simultaneously. When the
      standard was the isotopically labeled analogue of the target analyte, the
      information from the desorption process, i.e., time constant a, could be directly
      used for estimating the concentration of the target analyte. When the standard
      varied from the target analyte, the mass-transfer coefficient of the analyte
      could be extrapolated from that of the standard. These predictions agree well
      with experimental results. This approach facilitates the full integration of
      sampling, sample preparation, and sample introduction, especially for on-site or
      in vivo investigations, where the addition of standards to the sample matrix, or
      control of the velocity of the sample matrix, is very difficult.

PMID- 15456302
TI  - Effect of spacer arm length on protein retention on a strong cation exchange
      adsorbent.
AB  - The retention of five proteins was compared on a set of three strong cation
      exchange adsorbents that differed in spacer arm chemical structure and length.
      The adsorbents included a commercial product, Amersham Biosciences SP Sepharose
      Fast Flow, containing a six-carbon spacer between the agarose matrix and the
      anionic ligand, and two custom-prepared materials. One of the custom adsorbents
      contained a spacer of about half the length of the SP Sepharose Fast Flow, and
      the other contained no spacer arm. The adsorbent with no spacer arm was found to
      be significantly more retentive for all of the test proteins examined, in both
      isocratic and gradient elution tests. Reducing the spacer arm length by half
      resulted in increased retention for four of the five proteins, but this increase
      was less than what was observed when the spacer arm was eliminated. Retention
      increases were obtained without increasing the density of the anionic charge
      groups and appear to result from an enhancement of electrostatic or secondary
      nonelectrostatic interactions, or both. The results indicate that spacer arm
      length may be a useful variable in manipulating stationary-phase retention
      properties.

PMID- 15456303
TI  - High-speed electrochemically modulated liquid chromatography.
AB  - The performance advantages of carrying out electrochemically modulated liquid
      chromatography (EMLC) at elevated temperatures and mobile-phase flow rates are
      investigated. EMLC has the unique ability to manipulate analyte retention and
      enhance separation efficiencies through changes in the potential applied to a
      conductive stationary phase. Operation of high-performance liquid chromatography
      systems at elevated column temperatures also provides pathways to improve
      chromatographic performance by enhancing analyte diffusivity and facilitating the
      use of higher mobile-phase flow rates than conventionally attainable. The results
      show that performing EMLC separations at elevated temperatures (e.g., 100 degrees
      C) reduces the analysis time of a mixture of aromatic sulfonates in a mixed
      mobile phase by more than a factor of 20. Moreover, use of higher operating
      temperatures enables the separation of this mixture with an entirely aqueous
      mobile phase in less than 2 min.

PMID- 15456304
TI  - Measuring seven endogenous ketolic estrogens simultaneously in human urine by
      high-performance liquid chromatography-mass spectrometry.
AB  - A rapid, sensitive, and specific high-performance liquid chromatography
      electrospray ionization-multistage mass spectrometry (MS) method for measuring
      endogenous ketolic estrogen metabolites in human urine has been developed. The
      method requires a single hydrolysis/extraction/derivatization step and only 2.5
      mL of urine, yet is able to simultaneously quantify estrone and its 2-methoxy and
      2-, 4-, and 16alpha-hydroxy derivatives, 16-ketoestradiol, and 2-hydroxyestrone-3
      methyl ether metabolites. The combination of a simple hydrazone derivatization
      step with multistage MS greatly enhances the sensitivity and specificity of the
      analysis of endogenous estrogen within human urine. Standard curves are linear
      over a 100-fold concentration range with linear regression correlation
      coefficients typically greater than 0.99. The lower limit of quantitation for
      each ketolic estrogen is 0.2 ng/2.5-mL urine sample (10 pg on column), with an
      accuracy of 93-103% and an overall precision, including the hydrolysis,
      extraction, and derivatization steps, of 1-13% relative standard derivation (RSD)
      for samples prepared concurrently and 8-16% RSD for samples prepared in separate
      batches. This method also allows for the identification of 2-hydroxyestrone-3
      methyl ether in urine obtained from both pre- and postmenopausal women. This
      potentially protective estrogen metabolite has been previously reported only in
      the urine of pregnant women. Since individual patterns of estrogen metabolism may
      influence the risk of breast cancer, accurate and specific measurement of
      estrogen metabolites in biological matrixes will facilitate future research on
      breast cancer prevention, screening, and treatment.

PMID- 15456305
TI  - Preparative enantiomer separation of dichlorprop with a cinchona-derived chiral
      selector employing centrifugal partition chromatography and high-performance
      liquid chromatography: a comparative study.
AB  - A countercurrent chromatography protocol for support-free preparative enantiomer
      separation of the herbicidal agent 2-(2,4-dichlorphenoxy)propionic acid
      (dichlorprop) was developed utilizing a purposefully designed, highly
      enantioselective chiral stationary-phase additive (CSPA) derived from bis-1,4
      (dihydroquinidinyl)phthalazine. Guided by liquid-liquid extraction experiments, a
      solvent system consisting of 10 mM CSPA in methyl tert-butyl ether and 100 mM
      sodium phosphate buffer (pH 8.0) was identified as a suitable stationary/mobile
      phase combination. This solvent system provided an ideal compromise among
      stationary-phase retention, enantioselectivity, and well-balanced analyte
      distribution behavior. Using a commercial centrifugal partition chromatography
      instrument, complete enantiomer separations of up to 366 mg of racemic
      dichlorprop could be achieved, corresponding to a sample load being equivalent to
      the molar amount of CSPA employed. Comparison of the preparative performance
      characteristics of the CPC protocol with that of a HPLC separation using a silica
      supported bis-1,4-(dihydroquinidinyl)phthalazine chiral stationary phase CSP
      revealed comparable loading capacities for both techniques but a significantly
      lower solvent consumption for CPC. With respect to productivity, HPLC was found
      to be superior, mainly due to inherent flow rate restrictions of the CPC
      instrument. Given that further progress in instrumental design and engineering of
      dedicated, highly enantioselective CSPAs can be achieved, CPC may offer a viable
      alternative to CSP-based HPLC for preparative-scale enantiomer separation.

PMID- 15456306
TI  - Simultaneous determination of C1-C4 carboxylic acids and aldehydes using 2,4
      dinitrophenylhydrazine-impregnated silica gel and high-performance liquid
      chromatography.
AB  - A new method for the simultaneous determination of aliphatic carboxylic acids and
      aldehydes in air is described. In this work, carboxylic acids were allowed to
      react with 2,4-dinitrophenylhydrazine (DNPH) to form the corresponding carboxylic
      2,4-dinitrophenylhydrazides. These derivatives have excellent thermal stability,
      with melting points higher than those of the corresponding hydrazones by 32-50
      degrees C. C1-C4 carboxylic acid 2,4-dinitrophenylhydrazides exhibited maximum
      absorption wavelengths of 331-334 nm and molar absorption coefficients of 1.4 x
      10(4) L/mol/cm. They were completely separated by high-performance liquid
      chromatography (HPLC) with an RP-Amide C16 column. Cartridges packed with DNPH
      coated silica particles (DNPH cartridge) were used for sampling formic acid and
      aldehydes. Formic acid was physically adsorbed on the silica particles as the
      first step of the sampling mechanism. Gradual reaction with DNPH followed. Formic
      acid reacted very slowly with DNPH at room temperature (20 degrees C), but
      reacted completely at 80 degrees C over 4 h. In field measurements, the sample
      air was drawn through a DNPH cartridge. After sampling, the cartridges were
      heated at 80 degrees C for 5 h and extracted with acetonitrile for HPLC analysis.
      Under these optimized conditions, the LOD is 0.4 ug/m(3) for an air sample
      collected for 24 h at 100 mL/min (144 L).

PMID- 15456307
TI  - Chromatographic separation and multicollection-ICPMS analysis of iron.
      Investigating mass-dependent and -independent isotope effects.
AB  - A procedure was developed that allows precise determination of Fe isotopic
      composition. Purification of Fe was achieved by ion chromatography on AG1-X8
      strongly basic anion-exchange resin. No isotopic fractionation is associated with
      column chemistry within 0.02 per thousand /amu at 2sigma. The isotopic
      composition was measured with a Micromass IsoProbe multicollection inductively
      coupled plasma hexapole mass spectrometer. The Fe isotopic composition of the
      Orgueil CI1 carbonaceous chondrite, which best approximates the solar
      composition, is indistinguishable from that of IRMM-014 (-0.005 +/- 0.017 per
      thousand /amu). The IRMM-014 reference material is therefore used for
      normalization of the isotopic ratios. The protocol for analyzing mass-dependent
      variations is validated by measuring geostandards (IF-G, DTS-2, BCR-2, AGV-2) and
      heavily fractionated Fe left after vacuum evaporation of molten wustite (FeO) and
      solar (MgO-Al(2)O(3)-SiO(2)-CaO-FeO in chondritic proportions) compositions. It
      is shown that the isotopic composition of Fe during evaporation of FeO follows a
      Rayleigh distillation with a fractionation factor alpha equal to
      (m(1)/m(2)()1/2), where m(1) and m(2) are the masses of the considered isotopes.
      This agrees with earlier measurements and theoretical expectations. The isotopic
      composition of Fe left after vacuum evaporation of solar composition also follows
      a Rayleigh distillation but with a fractionation factor (1.013 22 +/- 0.000 67
      for the (56)Fe/(54)Fe ratio) that is lower than the square root of the masses
      (1.018 35). The protocol for analyzing mass-independent variations is validated
      by measuring terrestrial rocks that are not expected to show departure from mass
      dependent fractionation. After internal normalization of the (57)Fe/(54)Fe ratio,
      the isotopic composition of Fe can be measured accurately with precisions of
      0.2epsilon and 0.5epsilon at 2sigma for (56)Fe/(54)Fe and (58)Fe/(54)Fe ratios,
      respectively (epsilon refers to relative variations in parts per 10 000). For
      (58)Fe, this precision is an order of magnitude better than what had been
      achieved before. The method is applied to rocks that could potentially exhibit
      mass-independent effects, meteorites and Archaean terrestrial samples. The
      isotopic composition of a 3.8-Ga-old banded iron formation from Isua (IF-G,
      Greenland), and quartz-pyroxene rocks from Akilia and Innersuartuut (GR91-26 and
      SM/GR/171770, Greenland) are normal within uncertainties. Similarly, the Orgueil
      (CI1), Allende (CV3.2), Eagle Station (ESPAL), Brenham (MGPAL), and Old Woman
      (IIAB) meteorites do not show any mass-independent effect.

PMID- 15456308
TI  - Detection of phosphorylated peptides in proteomic analyses using microfluidic
      compact disk technology.
AB  - A compact disk (CD)-based microfluidic method for selective detection of
      phosphopeptides by mass spectrometry is described. It combines immobilized metal
      affinity chromatography (IMAC) and enzymatic dephosphorylation. Phosphoproteins
      are digested with trypsin and processed on the CD using nanoliter scale IMAC with
      and without subsequent in situ alkaline phosphatase treatment. This is followed
      by on-CD matrix-assisted laser desorption/ionization (MALDI) mass spectrometry.
      Dephosphorylation of the IMAC-enriched peptides allows selective phosphopeptide
      detection based on the differential mass maps generated (mass shifts of 80 Da or
      multiples of 80 Da). The CD contains 96 microstructures, each with a 16 nL IMAC
      microfluidic column. Movement of liquid is controlled by differential spinning of
      the disk. Up to 48 samples are distributed onto the CD in two equal sets. One set
      is for phosphopeptide enrichment only, the other for identical phosphopeptide
      enrichment but combined with in situ dephosphorylation. Peptides are eluted from
      the columns directly into MALDI target areas, still on the CD, using a solvent
      containing the MALDI matrix. After crystallization, the CD is inserted into a
      MALDI mass spectrometer for analysis down to the femtomole level. The average
      success rate in phosphopeptide detection is over 90%. Applied to noncharacterized
      samples, the method identified two novel phosphorylation sites, Thr 735 and Ser
      737, in the ligand-binding domain of the human mineralocorticoid receptor.

PMID- 15456309
TI  - Physicochemical properties determining the detection probability of tryptic
      peptides in Fourier transform mass spectrometry. A correlation study.
AB  - Sequence verification and mapping of posttranslational modifications require
      nearly 100% sequence coverage in the "bottom-up" protein analysis. Even in
      favorable cases, routine liquid chromatography-mass spectrometry detects from
      protein digests peptides covering 50-90% of the sequence. Here we investigated
      the reasons for limited peptide detection, considering various physicochemical
      aspects of peptide behavior in liquid chromatography-Fourier transform mass
      spectrometry (LC-FTMS). No overall correlation was found between the detection
      probability and peptide mass. In agreement with literature data, the signal
      increased with peptide hydrophobicity. Surprisingly, the pI values exhibited an
      opposite trend, with more acidic tryptic peptides detected with higher
      probability. A mixture of synthesized peptides of similar masses confirmed the
      hydrophobicity dependence but showed strong positive correlation between pI and
      signal response. An explanation of this paradoxal behavior was found through the
      observation that more acidic tryptic peptide lengths tend to be longer. Longer
      peptides tend to acquire higher average charge state in positive mode
      electrospray ionization than more basic but shorter counterparts. The induced
      current detection in FTMS favors ions in higher charge states, thus providing the
      observed pI-FTMS signal anticorrelation.

PMID- 15456310
TI  - Characterization of cellobiohydrolase I N-glycans and differentiation of their
      phosphorylated isomers by capillary electrophoresis-Q-Trap mass spectrometry.
AB  - A capillary electrophoresis-mass spectrometric (CE-MS) method is described for
      the simultaneous analysis of uncharged and charged glycans. The glycans were
      labeled with the negatively charged tag 8-aminopyrene-1,3,6-trisulfonate by
      reductive amination and separated in an ammonium acetate buffer. A Q-Trap
      instrument was used for mass spectrometric detection. The CE-MS method was first
      optimized using maltooligosaccharides and ribonuclease B N-glycans and then
      applied to the characterization of enzymatically released N-glycans from the
      glycoprotein cellobiohydrolase I. The method, as developed, allowed
      differentiation of phosphorylated isomers and MS/MS provided useful structural
      information. Further structural evidence was obtained by studying the methylated
      glycans in off-line ESI-MS/MS experiments and by using a combination of chemical
      and enzymatic sequencing.

PMID- 15456312
TI  - Improvement of the MS/MS fragment ion coverage of acidic residue-containing
      peptides by amidation with 15N-substituted amine.
AB  - Tandem mass spectrometry (MS/MS) is a powerful tool for peptide sequencing and
      characterization. However, the selective cleavage at acidic residues, aspartic
      acid, and glutamic acid prevents the generation of enough product ions to
      elucidate the entire sequence. We attempted to solve the problem by converting
      the residues into the corresponding amides, asparagine and glutamine. The
      amidation suppressed the cleavage at the converted residues, and the product ions
      derived from dissociation at other sites became abundant. Incorporation of
      nitrogen isotope (15)N in the amine constituent for amidation minimized the mass
      change from -0.984 016 to +0.013 019, allowing easy discrimination of acidic and
      amide residues in the original sequences by MS/MS database search. In addition,
      the amidated and unchanged peptides had the same nominal mass, even when the
      transformation was incomplete, which was approximately 70% in the current
      condition. The unmodified acidic residues remaining were rather useful to give
      marker fragments by the dominant dissociation. These results demonstrate that
      (15)N-amidation is effective in improving the performance of MS/MS to elucidate
      amino acid sequences of peptides.

PMID- 15456311
TI  - Infrared atmospheric pressure MALDI ion trap mass spectrometry of frozen samples
      using a Peltier-cooled sample stage.
AB  - Infrared atmospheric pressure matrix-assisted laser desorption/ionization on an
      ion trap mass spectrometer is used to analyze frozen samples generated using a
      Peltier-cooled sample stage. This allows for the analysis of samples in water
      without the addition of matrix, in near-native conditions, and with minimal loss
      of water due to evaporation. Analysis of frozen samples is extended to study
      peptides, carbohydrates, and glycolipids.

PMID- 15456313
TI  - Recycling size exclusion chromatography for the analysis and separation of
      nanocrystalline gold.
AB  - Recycling size exclusion chromatography (RSEC) provides a high-resolution
      technique for the analysis and separation of materials based on size. We show
      here the application of this method to gold nanocrystals stabilized by thiols.
      Alternate recycling is more effective at separating nanomaterials as compared to
      closed-loop recycling because of its improved efficiency and high resolution.
      With the use of this technique, we find the resolution ratio of nanocrystal
      separation increases with the square root of the cycle number, in good agreement
      with theory. The increased resolution of the size exclusion chromatograms permits
      the use of RSEC in the baseline separation of nanocrystals which differ by only 6
      A in size. In addition to separations, RSEC is valuable as an analytical tool.
      For example, after recycling processes an initially broad and chromatographic
      feature from a gold nanocrystal solution resolves into three distinct peaks.
      Transmission electron microscopy of collected fractions reveals that these peaks
      correspond to distinct populations of gold nanoparticles with narrowly defined
      sizes.

PMID- 15456314
TI  - Electrochemical detection of chloride by underpotentially deposited silver films
      on polycrystalline gold.
AB  - This paper describes an electrochemical method for measuring dilute levels of
      chloride using an underpotentially deposited (UPD) Ag adlayer on polycrystalline
      Au substrates as a sensing agent. Specifically, chloride ions adsorb onto the Ag
      UPD adlayer and effect changes in the electrochemical deposition and stripping
      characteristics of the silver film. Cyclic voltammograms (CVs) of the native
      Au/Ag(UPD) electrode in 0.1 M H2SO4(aq) exhibit a primary stripping peak for the
      Ag UPD adlayer at 550 mV vs Ag(+/0), and chloride adsorption onto the Au/Ag(UPD)
      surface effects a peak shift to approximately 600 mV vs Ag(+/0), depending on the
      amount of adsorbed Cl-, as affected by the Cl- concentrations and contact times
      employed in the derivatization. The chloride-treated electrodes also exhibit a
      stripping peak at 275 mV that is not observed on the native substrate and
      increases in intensity with Cl- concentration and derivatization time. The
      integrated charge density for this latter stripping peak relative to that for the
      primary stripping peak at 550-610 mV provides a useful metric for quantifying
      adsorbed Cl- levels, and these values allow measurement of Cl- concentrations in
      dilute aqueous solutions. For Cl- concentrations between 0.5 and 100 microM, the
      kinetics of Cl- adsorption followed a transient Langmuir adsorption model and
      allowed measured surface coverages to be used for determining Cl- solution
      concentrations. Using contact times of 1 min for Cl- adsorption, the electrodes
      showed a linear response across Cl- concentrations of 0.5-20 microM.

PMID- 15456315
TI  - In situ spectroelectrochemistry of poly(N,N'
      ethylenebis(salicylideneiminato)Cu(II)).
AB  - In situ ESR, UV-visible, and FT-IR-ATR spectroelectrochemistry were used to study
      the charge transfer for electrochemically synthesized poly(N,N'
      ethylenebis(salicylideneiminato)Cu(II)), which represents a macromolecular metal
      chelate with ESR-active central metal ions. Structural evidence for different
      charged states in electroactive poly(Cu(II)-salen) was obtained from ESR, UV
      visible, and FT-IR spectra under reversible redox cycling. The changes in a
      characteristic broad ESR line without hyperfine splitting originating from Cu(II)
      as well as in the corresponding UV-visible and infrared spectra are discussed in
      order to describe an electron transfer to the redox-active sites within the
      polymer chains in detail.

PMID- 15456316
TI  - Anodic stripping voltammetry of arsenic(III) using gold nanoparticle-modified
      electrodes.
AB  - A novel method for the detection of arsenic(III) in 1 M HCl at a gold
      nanoparticle-modified glassy carbon electrode has been developed. The gold
      nanoparticles were electrodeposited onto the glassy carbon electrode via a
      potential step from +1.055 to -0.045 V vs SCE for 15 s from 0.5 M H2SO4
      containing 0.1 mM HAuCl4. The resulting electrode surfaces were characterized
      with both AFM and cyclic voltammetry. Anodic stripping voltammetry of
      arsenic(III) on the modified electrode was performed. After optimization, a LOD
      of 0.0096 ppb was obtained with LSV.

PMID- 15456317
TI  - Sensitive electrochemical determination of unlabeled MutS protein and detection
      of point mutations in DNA.
AB  - MutS protein plays an important role in the DNA repair system in prokaryotic and
      eukaryotic cells; it recognizes unpaired and mispaired bases in duplex DNA and
      can be used for detection of point mutations in vitro. We have shown that small
      amounts of this protein can be detected electrochemically at mercury and carbon
      electrodes without any labeling. Using constant current stripping analysis (CPSA)
      and mercury electrodes, tens of attomoles of this protein can be detected. The
      sensitivity of the determination at carbon electrodes is by more than 3 orders of
      magnitude lower. Using biotinylated DNA duplexes attached to magnetic beads,
      single-base mismatches and insertion/deletions were recognized by MutS. Picogram
      amounts of this protein were detected by CPSA after MutS releasing from the
      beads.

PMID- 15456318
TI  - Neutral reagents in solutions with low content of supporting electrolyte: how to
      determine the steady-state conditions.
AB  - Cyclic voltammograms obtained at ultramicroelectrodes in the electrochemical
      systems where an uncharged reactant is significantly more concentrated than the
      supporting electrolyte show an unusual feature. The forward and the backward
      waves cross over, forming a hysteresis loop. The width of the hysteresis
      increases with the relative concentration of the reactant, with the electrode
      size, and with the scan rate. We show that the reason for this hysteresis is the
      slow transport of supporting electrolyte ions that are necessary to compensate
      the charge of the reaction product. As a result, the steady-state concentration
      profile of counterions is reached significantly slower than the steady-state
      concentration gradient of the reactant, and the counterion transport determines
      how rapidly the steady state for the whole system is approached. The scan rate
      yielding near-steady-state voltammograms can differ by more than 1 order of
      magnitude for systems with high and low concentrations of supporting electrolyte.
      Experimental evidence for this, supported by digital simulation results, is
      presented. The appropriate criterion for assessing the steady state in such
      systems is thus the identity of the forward and backward scans, without
      hysteresis. If this condition is not fulfilled, the formal potentials and the
      related parameters determined from the obtained voltammograms may be erroneous.

PMID- 15456319
TI  - Electrochemical quartz crystal nanobalance to detect solvent displacement by pH
      induced conformational changes of proteins at Pt.
AB  - The electrochemical quartz crystal nanobalance (EQCN) techniques of simultaneous
      measurements of frequency and cyclic voltammetry (CV) were used to investigate
      protein adsorption behavior resulting from pH-induced conformational changes at
      the Pt electrode at 298 K. The adsorption behavior of holo- and apo-alpha
      lactalbumin was studied in electrolyte solutions of pH < 2, 7.4, and 11. The EQCN
      frequency measurements did not directly monitor the mass of the adsorbed protein
      at anodic potentials, but instead, at a potential characteristic of the double
      layer for platinum, gave a measure of the extent of solvent displacement by the
      adsorbed protein (i.e., a "footprint"), which correlated well with known pH
      induced conformational changes of the protein. Simultaneous CV charge transfer
      measurements provided information on the number of layers of protein adsorbed to
      the surface. This ability of the EQCN to detect solvent displacement by protein
      adsorption is potentially useful for biosensors to detect and to monitor protein
      conformational changes in the bulk and during the adsorption process. The
      Langmuir adsorption isotherm provided the Gibbs energy of adsorption,
      DeltaG(ADS), and showed excellent agreement between the CV and EQCN frequency
      measurements.

PMID- 15456320
TI  - Kinetics of ion-exchange binding of redox metal cations to thiolate-DNA
      monolayers on gold.
AB  - The ion-exchange kinetics of metal cation binding to and dissociation from
      thiolate-DNA monolayers on gold can be monitored by a simple electrochemical
      protocol. The apparent first-order rate constants were obtained by analyzing the
      time-dependent voltammetric behavior of the redox cation [Ru(NH3)6]3+. It was
      found that the binding kinetics is dominated by the structural nature of the
      film; i.e., the apparent first-order rate constant (kapp) decreases significantly
      upon increasing the surface density of DNA strands. Dissociation rate constants
      were obtained by transferring the incubated electrode into redox-free buffer
      solution. The kinetic data augment our fundamental understanding of metal ion-DNA
      interactions and are critical to ensure the accuracy and reliability of
      experimental DNA detection protocols.

PMID- 15456321
TI  - Single-molecule reader for high-throughput bioanalysis.
AB  - We report here the development of a device for single-molecule imaging on large
      surface areas. A CCD camera operated in time delay and integration mode is
      synchronized with the movement of a sample scanning stage, enabling continuous
      data acquisition. Experiments on single fluorescent lipid molecules in supported
      lipid bilayers and on stained living cells demonstrate the capabilities of the
      method. Areas of up to 5 x 5 mm(2) were recorded within 11 min at a pixel size of
      129 nm.

PMID- 15456322
TI  - Analysis of C2H4 in C2H6 and C2H5D with VUV absorption spectroscopy and a method
      to remove C2H4 from C2H6 and C2H5D.
AB  - The photoabsorption cross section of C2H4 was measured in the spectral region 107
      183 nm and those of C2H6 and C2H5D were accurately determined in the spectral
      region 107-162 nm using radiation from a synchrotron as source of VUV light.
      Typically, C2H4 present as a minor impurity in samples of C2H6 and C2H5D
      distorted the absorption cross section in curves of C2H6 and C2H5D in the onset
      region. We completely eliminated C2H4 from C2H6 and C2H5D using adsorption on
      activated Pd/charcoal at 195 K. By this means, we detected no C2H4 in samples of
      C2H6 and C2H5D according to their absorption spectra. The detection limit of C2H4
      in C2H6 and C2H5D is less than 0.03 ppm with VUV absorption spectroscopy.

PMID- 15456323
TI  - Online CE-MALDI-TOF MS using a rotating ball interface.
AB  - We report on the construction and performance of a rotating ball interface for
      online coupling of capillary electrophoresis (CE) to matrix-assisted laser
      desorption ionization (MALDI) mass spectrometry with a time-of-flight (TOF) mass
      analyzer. The interface is based on a rotating stainless steel ball that
      transports samples from atmospheric pressure to the high vacuum of the mass
      spectrometer for desorption and ionization. The sample is deposited directly from
      a 50-microm-i.d. separation capillary onto the 19-mm ball that is rotating at
      0.03 to 0.3 rpm. The sample is mixed online with matrix flowing from a separate
      50-microm-i.d. capillary. The sample deposit dries before it is rotated past a
      polymer gasket and into the laser ionization region. Cleaning of the interface is
      accomplished using solvent-saturated felt, which cleans the ball surface after it
      rotates out of the ionization chamber. On-line CE-MALDI is demonstrated, and the
      performance is evaluated with the analysis of a mixture of three peptides: [Lsy8]
      vasopressin, substance P, and neurotensin. The rotating ball interface to MALDI
      TOF MS demonstrated mass detection limit in the high femtomole range. The
      interface has negligible memory effect and shows no significant electrophoretic
      peak broadening when operated under optimized conditions.

PMID- 15456324
TI  - Implantable flow-through capillary-type microdialyzers for continuous in situ
      monitoring of environmentally relevant parameters.
AB  - In this paper, a simple, flexible, and cost-effective flow-through microdialyzer
      hyphenated with a miniaturized differential potentiometric detector is proposed
      for continuous diffusion-controlled sampling of analytes of environmental
      interest. The analytical performance of the dedicated configuration involving
      merely a single cellulose regenerated hollow fiber is critically compared with
      that of commercially available concentric probes commonly exploited for in vivo
      monitoring of the extracellular space in living tissues and that of large
      dialysis-based probes furnished with flat membranes. The outstanding feature of
      the capillary-type design is the ability of adapting the extraction fractions
      (EF) to the requirements of the assays and flow-through detectors by selection of
      appropriate membrane length/perfusion rate ratios. Passive sampling under steady
      state conditions (EF approximately 100%) has proven feasible for environmentally
      relevant ions, such as chloride, by perfusing a 3-cm-long capillary with water at
      a flow rate of 2.0 microL/min. Hence, there is no need for recalibration of the
      flow setup after implantation of the purpose-made probe. The effect of physical
      and chemical variables on the diffusive flux is discussed in detail for the
      various flow-through membrane separation devices assessed. Effective means to
      attain identical dialysate concentrations of target species under dynamic regime
      irrespective of the matrix ingredients are also presented. The dedicated
      microdialyzer features extreme tolerance to high molecular weight interfering
      matrix compounds (> or =5000 mg/L humic acid) at the 5% interference level, which
      makes it especially suited for the interference-free potentiometric determination
      of ionic species in environmental samples containing high levels of organic
      matter. The potentials of the membrane separation unit were assessed for
      continuous monitoring of chemical changes in the interstitial/pore water of
      organic soils via stimulus-response strategies.

PMID- 15456326
TI  - Options for treatment of primary biliary cirrhosis.
AB  - Primary biliary cirrhosis (PBC) is a chronic progressive cholestatic disease
      where there is progressive, granulomatous destruction of the middle-sized bile
      ducts. The disease affects mainly middle-aged women. The association with other
      autoimmune diseases and the widespread disturbance of the humoral and cellular
      immune systems has led to the inclusion of PBC as an autoimmune disease. However,
      there are several lines of evidence that suggest that both host and environmental
      factors are implicated in triggering the disease. Without a clear aetiology, it
      is difficult to find a logical approach to treatment. Well constructed clinical
      trials are difficult to run because of the variable and long natural history of
      the disease; and suitable endpoints are difficult to define and validated
      surrogate endpoints have not been defined. The only drug licensed for use is the
      bile acid, ursodeoxycholic acid. This drug is associated with significant
      biochemical improvement and improvement in the immunological disturbances
      (including a reduction in the titre of the diagnostic autoantibody,
      antimitochondrial antibody), but the effect on survival and histological
      progression is still controversial. There is little effect on symptoms.
      Nonetheless, its safety and lack of toxicity have meant that it has become the
      drug of choice and most studies now assess the effect of additional treatments.
      Many other agents have been studied. There is some evidence, from prospective,
      controlled studies, for a beneficial effect of azathioprine and ciclosporin
      (cyclosporine); evidence for a beneficial effect of corticosteroids and of
      mycophenolate is limited and there is little firm evidence for a beneficial
      effect of methotrexate, penicillamine, thalidomide or colchicine. Other
      treatments being evaluated include fibric acid derivatives (fibrates), NSAIDs and
      leukotriene antagonists. Liver transplantation remains the only option for end
      stage disease but recurrence of disease may be found in the graft. Experimental
      therapies include antiretroviral therapy. Symptomatic treatment is required for
      pruritus and the mainstays are the bile acid binding agents such as
      colestyramine. For those who are intolerant of the drug or where it is
      ineffective, rifampicin and naltrexone may be effective. There is no effective
      treatment for the associated lethargy.

PMID- 15456327
TI  - Slowing the progression of adult chronic kidney disease: therapeutic advances.
AB  - When kidney disease of any aetiology results in substantial loss of nephrons, a
      common clinical syndrome, characterised by hypertension, proteinuria and a
      progressive decline in renal function, ensues. This observation suggests that
      common mechanisms may contribute to progressive renal injury and that therapeutic
      interventions that inhibit these common pathways may afford renal protection.
      Research to date has identified several mechanisms that may contribute to
      progressive renal injury including glomerular haemodynamic changes, multiple
      effects of angiotensin II and detrimental effects of excessive filtration of
      plasma proteins by injured glomeruli. Clinical trials over the past decade have
      identified several interventions that are effective in slowing the rate of
      progression of chronic kidney disease (CKD). The use of ACE inhibitors,
      angiotensin receptor antagonists or a combination of the two should be regarded
      as fundamental to any therapy for slowing the rate of CKD progression.
      Hypertension should be treated aggressively to achieve a blood pressure target of
      < 130/80 mm Hg. Reduction of proteinuria to < 0.5 g/day should be regarded as an
      independent therapeutic goal. Although inconclusive, there is some evidence to
      support moderate dietary protein restriction to 0.6 g/kg/day in appropriate
      patients. Hyperlipidaemia may contribute to CKD progression and should be treated
      to reduce cardiovascular risk and potentially improve renal protection. Smoking
      cessation should be encouraged and, where necessary, assisted. Among diabetic
      patients tight glycaemic control should be achieved (glycosylated haemoglobin <
      7%). These interventions are simple and relatively inexpensive. If applied to all
      patients with CKD they will result in substantial slowing of renal function
      decline in many patients and thereby reduce the number who progress to end-stage
      renal disease and require renal replacement therapy.

PMID- 15456328
TI  - Antipsychotic-induced hyperprolactinaemia: mechanisms, clinical features and
      management.
AB  - Hyperprolactinaemia is an important but neglected adverse effect of antipsychotic
      medication. It occurs frequently with conventional antipsychotics and some
      atypical antipsychotics (risperidone and amisulpride) but is rare with other
      atypical antipsychotics (aripiprazole, clozapine, olanzapine, quetiapine,
      ziprasidone). For this reason the terms 'prolactin-sparing' and 'prolactin
      raising' are more useful than 'atypical' and 'conventional' when considering the
      effect of antipsychotic drugs on serum prolactin. During antipsychotic treatment
      prolactin levels can rise 10-fold or more above pretreatment values. In a recent
      study approximately 60% of women and 40% of men treated with a prolactin-raising
      antipsychotic had a prolactin level above the upper limit of the normal range.
      The distinction between asymptomatic and symptomatic hyperprolactinaemia is
      important but is often not made in the literature. Some symptoms of
      hyperprolactinaemia result from a direct effect of prolactin on target tissues
      but others result from hypogonadism caused by prolactin disrupting the normal
      functioning of the hypothalamic-pituitary-gonadal axis. Symptoms of
      hyperprolactinaemia include gynaecomastia, galactorrhoea, sexual dysfunction,
      infertility, oligomenorrhoea and amenorrhoea. These symptoms are little
      researched in psychiatric patients. Existing data suggest that they are common
      but that clinicians underestimate their prevalence. For example, well conducted
      studies of women treated with conventional antipsychotics have reported
      prevalence rates of approximately 45% for oligomenorrhoea/amenorrhoea and 19% for
      galactorrhoea. An illness-related under-function of the hypothalamic-pituitary
      gonadal axis in female patients with schizophrenia may also contribute to
      menstrual irregularities. Long-term consequences of antipsychotic-related
      hypogonadism require further research but are likely and include premature bone
      loss in men and women. There are conflicting data on whether hyperprolactinaemia
      is associated with an increased risk of breast cancer in women. In patients
      prescribed antipsychotics who have biochemically confirmed hyperprolactinaemia it
      is important to exclude other causes of prolactin elevation, in particular
      tumours in the hypothalamic-pituitary area. If a patient has been amenorrhoeic
      for 1 year or more, investigations should include bone mineral density
      measurements. Management should be tailored to the individual patient. Options
      include reducing the dose of the antipsychotic, switching to a prolactin-sparing
      agent, prescribing a dopamine receptor agonist and prescribing estrogen
      replacement in hypoestrogenic female patients. The efficacy and risks of the last
      two treatment options have not been systematically examined. Antipsychotic
      induced hyperprolactinaemia should become a focus of interest in the drug
      treatment of psychiatric patients, particularly given the recent introduction of
      prolactin-sparing antipsychotics. Appropriate investigations and effective
      management should reduce the burden of adverse effects and prevent long-term
      consequences.

PMID- 15456329
TI  - Nabumetone: therapeutic use and safety profile in the management of
      osteoarthritis and rheumatoid arthritis.
AB  - Nabumetone is a nonsteroidal anti-inflammatory prodrug, which exerts its
      pharmacological effects via the metabolite 6-methoxy-2-naphthylacetic acid (6
      MNA). Nabumetone itself is non-acidic and, following absorption, it undergoes
      extensive first-pass metabolism to form the main circulating active metabolite (6
      MNA) which is a much more potent inhibitor of preferentially cyclo-oxygenase
      (COX)-2. The three major metabolic pathways of nabumetone are O-demethylation,
      reduction of the ketone to an alcohol, and an oxidative cleavage of the side
      chain occurs to yield acetic acid derivatives. Essentially no unchanged
      nabumetone and < 1% of the major 6-MNA metabolite are excreted unchanged in the
      urine from which 80% of the dose can be recovered and another 10% in faeces.
      Nabumetone is clinically used mainly for the management of patients with
      osteoarthritis (OA) or rheumatoid arthritis (RA) to reduce pain and inflammation.
      The clinical efficacy of nabumetone has also been evaluated in patients with
      ankylosing spondylitis, soft tissue injuries and juvenile RA. The optimum oral
      dosage of nabumetone for OA patients is 1 g once daily, which is well tolerated.
      The therapeutic response is superior to placebo and similar to nonselective COX
      inhibitors. In RA patients, nabumetone 1 g at bedtime is optimal, but an
      additional 0.5-1 g can be administered in the morning for patients with
      persistent symptoms. In RA, nabumetone has shown a comparable clinical efficacy
      to aspirin (acetylsalicylic acid), diclofenac, piroxicam, ibuprofen and naproxen.
      Clinical trials and a decade of worldwide safety data and long-term postmarketing
      surveillance studies show that nabumetone is generally well tolerated. The most
      frequent adverse effects are those commonly seen with COX inhibitors, which
      include diarrhoea, dyspepsia, headache, abdominal pain and nausea. In common with
      other COX inhibitors, nabumetone may increase the risk of GI perforations,
      ulcerations and bleedings (PUBs). However, several studies show a low incidence
      of PUBs, and on a par with the numbers reported from studies with COX-2 selective
      inhibitors and considerably lower than for nonselective COX inhibitors. This has
      been attributed mainly to the non-acidic chemical properties of nabumetone but
      also to its COX-1/COX-2 inhibitor profile. Through its metabolite 6-MNA,
      nabumetone has a dose-related effect on platelet aggregation, but no effect on
      bleeding time in clinical studies. Furthermore, several short-term studies have
      shown little to no effect on renal function. Compared with COX-2 selective
      inhibitors, nabumetone exhibits similar anti-inflammatory and analgesic
      properties in patients with arthritis and there is no evidence of excess GI or
      other forms of complications to date.

PMID- 15456331
TI  - Moxifloxacin: a review of its use in the management of bacterial infections.
AB  - Moxifloxacin (Avelox) is a fluoroquinolone antibacterial with a methoxy group in
      the C-8 position and a bulky C-7 side chain. Moxifloxacin is approved for use in
      the treatment of acute exacerbations of chronic bronchitis (AECB), community
      acquired pneumonia (CAP), acute bacterial sinusitis and uncomplicated skin and
      skin structure infections (approved indications may differ between countries).
      Moxifloxacin has a broad spectrum of antibacterial activity, including activity
      against penicillin-resistant Streptococcus pneumoniae. It achieves good tissue
      penetration and has a convenient once-daily administration schedule, as well as
      being available in both intravenous and oral formulations in some markets.
      Moxifloxacin has good efficacy in the treatment of patients with AECB, CAP, acute
      bacterial sinusitis and uncomplicated skin and skin structure infections, and is
      generally well tolerated. Thus, moxifloxacin is an important option in the
      treatment of bacterial infections.

PMID- 15456332
TI  - Reactive oxygen species in the cerebral circulation: physiological roles and
      therapeutic implications for hypertension and stroke.
AB  - It is now clear that reactive oxygen species (ROS) can act as signalling
      molecules in the cerebral circulation under both physiological and pathological
      conditions. Some major products of superoxide (O(2)(.)(-)) metabolism, such as
      hydrogen peroxide (H(2)O(2)) and hydroxyl radical (OH(.)), appear to be
      particularly good cerebral vasodilators and may, surprisingly, represent
      important molecules for increasing local cerebral blood flow. A major determinant
      of overall ROS levels in the cerebral circulation is the rate of generation of
      the parent molecule, O(2)(.)(-). Although the major enzymatic source of O(2)(.)(
      ) in cerebral arteries is yet to be conclusively established, the two most likely
      candidates are cyclo-oxygenase and nicotinamide adenine dinucleotide phosphate
      (reduced form) [NADPH] oxidase. The activity of endogenous superoxide dismutases
      (SODs) play a vital role in determining levels and effects of all individual ROS
      derived from metabolism of O(2)(.)(-). The term 'oxidative stress' may be an over
      simplification that hides the complexity and diversity of the ROS family in
      cerebrovascular health and disease. Although a generalised increase in ROS levels
      seems to occur during several vascular disease states, the consequences of this
      for cerebrovascular function are still unclear. Because enhanced breakdown of
      O(2)(.)(-) by SOD will increase the generation of the powerful cerebral
      vasodilator H(2)O(2), this latter molecule could conceivably act as a
      compensatory vasodilator mechanism in the cerebral circulation under conditions
      of elevated O(2)(.)(-) production. Some recent clinical data support the concept
      of a protective role for cerebrovascular NADPH oxidase activity. Although it is
      quite speculative at present, if NADPH oxidase were to emerge as a major source
      of beneficial vasodilator ROS in the cerebral circulation, this may represent a
      significant dilemma for treatment of ischaemic cerebrovascular conditions, as
      excessive NADPH oxidase activity is associated with the progression of several
      systemic vascular disease states, including hypertension and atherosclerosis.
      Despite data suggesting that antioxidant vitamins can have beneficial effects on
      vascular function and that their plasma levels are inversely correlated with risk
      of cardiovascular disease and stroke, the results of several recent large-scale
      clinical trials of antioxidant supplementation have been disappointing. Future
      work must establish whether or not increased ROS generation is necessarily
      detrimental to cerebral vascular function, as has been generally assumed, or
      whether localised increases in ROS in the vicinity of the arterial wall could be
      beneficial in disease states for the maintenance of cerebral blood flow.

PMID- 15456333
TI  - Management of invasive candidiasis in critically ill patients.
AB  - Candida species have become predominant pathogens in critically ill patients. In
      this population, invasive candidiasis is associated with a poor prognosis but
      adequate management can limit the attributable mortality. Adequate management,
      however, is hampered by a problematic diagnosis as the clinical picture of
      invasive disease is non-specific and blood cultures have a low sensitivity.
      Moreover, it is often hard to differentiate colonisation from infection and many
      critically ill patients are heavily colonised with Candida species, especially
      when receiving broad-spectrum antibacterials. The question of which antifungal
      agent to choose has become more complex as the development of new drugs raises
      promising expectations. Until the 1980s therapy for invasive candidiasis was
      limited to amphotericin B, but with the advent of new antifungal agents, such as
      azoles and echinocandins, less toxic therapeutic options are possible and doors
      have opened towards prevention and optimised therapy in the case of documented
      candidiasis. Through the arrival of these new antifungal agents, a range of
      therapeutic strategies for the management of invasive candidiasis has been
      developed: antifungal prophylaxis, pre-emptive therapy, and empirical and
      definitive antifungal therapy. Each of these strategies has a specific target
      population, as defined by specific underlying conditions and/or individual risk
      factors. Antifungal prophylaxis, in order to prevent candidal infection, is based
      on the type of underlying diseases with a high risk for invasive candidiasis.
      Individual risk factors are not taken into account. Potential indications are
      bone marrow transplantation, liver transplantation, recurrent gastrointestinal
      perforations or leakages, and surgery for acute necrotising pancreatitis. Pre
      emptive therapy is also a preventive strategy. It can be recommended on the basis
      of an individual risk profile including overt candidal colonisation. Empirical
      therapy is started in patients with a risk profile for invasive candidiasis. It
      is recommended in the presence of clinical signs of infection, deteriorating
      clinical parameters, or a clinical picture of infection not responding to
      antibacterials but in the absence of a clear causative pathogen. Definitive
      antifungal therapy is defined as therapy in patients with documented invasive
      infection. The main goal is to maintain a balance between optimal prevention and
      timely initiation of therapy on one hand, and to minimise selection pressure in
      order to avoid a shift towards less susceptible Candida species on the other
      hand.

PMID- 15456334
TI  - Role of fibric acid derivatives in the management of risk factors for coronary
      heart disease.
AB  - Although elevated low-density lipoprotein (LDL)-cholesterol is a well established
      coronary heart disease (CHD) risk factor, the ability to adequately discriminate
      high-risk individuals by this risk factor alone is limited and other metabolic
      risk variables are known to modulate CHD risk. For instance, it has been reported
      that the cluster of metabolic disturbances observed among individuals with
      abdominal obesity, the so-called metabolic syndrome, is associated with a
      substantially increased risk of CHD. Among the features of the dyslipidaemic
      profile observed in these individuals, the high triglyceride-low high-density
      lipoprotein (HDL)-cholesterol dyslipidaemia is predictive of an elevated risk of
      CHD. Fibric acid derivatives (fibrates) have been used in clinical practice for
      more than 2 decades as a class of agents known to decrease triglyceride levels
      while substantially increasing HDL-cholesterol levels, with a limited but
      significant additional lowering effect on LDL-cholesterol levels. Although the
      clinical benefits of HMG-CoA reductase inhibitors (statins) have been well
      documented by primary and secondary prevention trials that justify their
      widespread use, it was not until the publication of the VA-HIT (Veterans Affairs
      High-Density Lipoprotein Intervention Trial) that the relevance of identifying
      HDL-cholesterol as a therapeutic target to reduce the risk of recurrent CHD
      events was finally confirmed. The clinical benefits of fibrate therapy are
      especially important in the subpopulation of patients with low HDL-cholesterol
      levels with the metabolic syndrome, particularly in patients with type 2 diabetes
      mellitus or in abdominally obese, hyperinsulinaemic patients. Evidence also
      suggests that there is a 'fibrate effect' that mediates the reduction in CHD risk
      beyond the favourable impact of these agents on HDL-cholesterol levels. This last
      notion is consistent with the pleiotropic effects of fibrates which are known to
      be related to their mechanisms of action. Through peroxisome proliferator
      activated alpha-receptors, fibrates have a significant impact on the synthesis of
      several apolipoproteins (apo) and enzymes of lipoprotein metabolism as well as on
      the expression of several genes involved in fibrinolysis and inflammation.
      Fibrate therapy has been reported to decrease apo CIII levels (a powerful
      inhibitor of lipoprotein lipase) and increase apo AI levels, as well as to
      increase lipoprotein lipase activity. Such changes contribute to improve the
      catabolism of triglyceride-rich lipoproteins, leading to a substantial increase
      in HDL-cholesterol levels accompanied by a shift in the size and density of LDL
      particles (from small, dense LDL particles to larger, more buoyant cholesteryl
      ester-rich LDL). It is proposed that some of these pleiotropic effects could
      explain some of the clinical benefits of fibrate therapy beyond its HDL-raising
      properties, particularly among patients with abdominal obesity, hyperinsulinaemia
      or type 2 diabetes with both low HDL- and low/normal LDL-cholesterol levels.

PMID- 15456335
TI  - Antiepileptic drugs in the treatment of anxiety disorders: role in therapy.
AB  - Pharmacotherapy for anxiety disorders is an active area of research. A variety of
      drug groups have been shown to be effective in treating many of the anxiety
      disorders, with selective serotonin reuptake inhibitors (SSRIs) being considered
      first-line agents for virtually all anxiety disorders. There is a clinical need
      for alternative drug treatments, as many patients do not achieve a complete
      response and experience significant adverse effects. The successful use of
      antiepileptic drugs in mood disorders has led clinicians and researchers to
      investigate their potential efficacy in other psychiatric disorders, particularly
      in anxiety disorders. There have been a number of investigations conducted in the
      form of case reports, case series and open-label trials, suggesting the potential
      usefulness of antiepileptic drug treatment in a variety of anxiety disorders.
      More reliable evidence for the use of antiepileptic drugs in anxiety disorders
      can be gleaned from recent placebo-controlled trials. Thus far, the strongest
      placebo-controlled evidence has demonstrated the efficacy of pregabalin in
      treating social phobia and generalised anxiety disorder, while smaller or less
      robust controlled trials have suggested the potential efficacy of gabapentin in
      social phobia, lamotrigine in post-traumatic stress disorder, and valproic acid
      in panic disorder. Antiepileptic drugs may have a place in the treatment of
      anxiety disorders; however, further investigation is warranted to determine in
      what circumstances they should be used as monotherapy or as augmenting agents in
      individuals who are partially or non-responsive to conventional therapy.

PMID- 15456336
TI  - Prulifloxacin.
AB  - Prulifloxacin, the prodrug of ulifloxacin, is a broad-spectrum oral
      fluoroquinolone antibacterial agent. After absorption, prulifloxacin is
      metabolised by esterases to ulifloxacin. The drug has a long elimination half
      life, allowing once-daily administration. Ulifloxacin is generally more active in
      vitro than other fluoroquinolones against a variety of clinical isolates of Gram
      negative bacteria, including community and nosocomial isolates of Escherichia
      coli, Klebsiella spp., Proteus, Providencia and Morganella spp., Moraxella
      catarrhalis and Haemophilus spp. The activity of ulifloxacin against Pseudomonas
      aeruginosa varies between countries. Gram-positive organisms, including
      meticillin- or oxacillin-susceptible Staphylococcus aureus, Enterococcus spp. and
      Italian community isolates of Streptococcus pneumoniae are susceptible to
      ulifloxacin. Activity against Spanish strains of S. pneumoniae is moderate. In
      well designed clinical trials, good clinical and bacteriological efficacy
      (similar to that of ciprofloxacin, amoxicillin/clavulanic acid or pefloxacin) was
      seen with prulifloxacin 600 mg once daily for 10 days in patients with acute
      exacerbations of chronic bronchitis or complicated lower urinary tract infections
      (UTIs), and with single-dose prulifloxacin 600 mg in acute, uncomplicated lower
      UTIs. Prulifloxacin was generally well tolerated in clinical trials, with a
      similar tolerability profile to that of ciprofloxacin.

PMID- 15456339
TI  - Lumiracoxib.
AB  - Lumiracoxib is a highly selective and potent cyclo-oxygenase (COX)-2 inhibitor,
      with a novel structure that conveys weakly acidic properties and a unique
      pharmacological profile. It is rapidly absorbed, with a relatively short plasma
      half-life. In well designed clinical trials of 1-52 weeks' duration in patients
      with osteoarthritis (OA) or rheumatoid arthritis, the efficacy of oral
      lumiracoxib 100-400 mg/day in decreasing pain intensity and improving functional
      status was greater than that with placebo and similar to those with nonselective
      NSAIDs or celecoxib 200mg once daily. In single- and multiple-dose well designed
      trials in patients with acute pain associated with primary dysmenorrhoea, dental
      or orthopaedic surgery or tension-type headache, lumiracoxib 100-800 mg once
      daily was more effective in relieving acute pain than placebo or controlled
      release oxycodone 20 mg, and was at least as effective as selective COX-2
      inhibitors or nonselective NSAIDs. Lumiracoxib was generally well tolerated in
      clinical trials, with a similar overall tolerability profile to those of placebo
      and other COX-2-selective inhibitors. In a large 52-week safety trial in patients
      with OA, lumiracoxib 400mg once daily had a rate of gastrointestinal ulcer
      complications that was approximately one-third to one-quarter of that of
      ibuprofen 800 mg three times daily or naproxen 500 mg twice daily. Lumiracoxib
      was not associated with an increase in cardiovascular events.

PMID- 15456342
TI  - Anidulafungin.
AB  - Anidulafungin is a novel antifungal agent which, like other echinocandins,
      inhibits beta-(1,3)-D-glucan synthase and disrupts fungal cell-wall synthesis. It
      has marked antifungal activity against a broad spectrum of Candida spp. and
      Aspergillus spp., including amphotericin B- and triazole-resistant strains. In
      clinical trials, anidulafungin has primarily been evaluated in patients with
      oesophageal and invasive candidiasis. Preliminary data are emerging for other
      indications such as invasive aspergillosis. In a large, multicentre, double
      blind, double-dummy, randomised trial in patients with oesophageal candidiasis,
      intravenous anidulafungin 50 mg/day was as effective as oral fluconazole 100
      mg/day regarding end-of-treatment rates of endoscopic cure and clinical and
      microbiological success. Duration of treatment was approximately 2-3 weeks, and
      patients in both groups received a loading dose of study drug (twice the daily
      maintenance dose) on day 1. Anidulafungin is generally well tolerated. Across the
      dosage range 50-100 mg/day, adverse events appear not to be dose- or infusion
      related. In the largest clinical trial to date, the most common treatment-related
      adverse events were phlebitis/thrombophlebitis, headache, nausea, vomiting and
      pyrexia.

PMID- 15456345
TI  - Non-intentional doping in sports.
AB  - Compulsory drug testing was introduced in 1968 by the International Olympic
      Committee. Since then, several doping cases have been reported in sports
      competition world wide. Positive results are based on the detection of prohibited
      substances, their metabolites and markers in biological (mainly urine) samples
      supplied by athletes. In some cases, the evidences were not contested and
      athletes admitted the use of banned substances. However, in other cases, athletes
      denied the use of doping to enhance performance and claimed to have inadvertently
      or passively absorbed the drug. Unfortunately, no current accepted analytical
      method is capable of distinguishing between a sample from a cheater and one from
      an athlete who was passively exposed to a doping agent. Athletes' allegations
      have included the passive inhalation of drug smoke (e.g. marijuana) or the
      ingestion of food or products sold as nutritional supplements that contained
      prohibited substances. In the scientific literature, several studies have been
      performed to investigate the possibility of an accidental exposure being the
      reason for the appearance of detectable quantities of banned substances in urine
      samples. Based on these studies, this article discusses those cases where the
      athlete's claims could be possible in generating a positive result in doping
      control and in which circumstances it would be improbable to happen.

PMID- 15456346
TI  - Airline chair-rest deconditioning: induction of immobilisation thromboemboli?
AB  - Air passenger miles will likely double by year 2020. The altered and restrictive
      environment in an airliner cabin can influence haematological homeostasis in
      passengers and crew. Flight-related deep venous thromboemboli (DVT) have been
      associated with at least 577 deaths on 42 of 120 airlines from 1977 to 1984 (25
      deaths/million departures), whereas many such cases go unreported. However, there
      are four major factors that could influence formation of possible flight-induced
      DVT: sleeping accommodations (via sitting immobilisation); travellers' medical
      history (via tissue injury); cabin environmental factors (via lower partial
      pressure of oxygen and lower relative humidity); and the more encompassing chair
      rest deconditioning (C-RD) syndrome. There is ample evidence that recent injury
      and surgery (especially in deconditioned hospitalised patients) facilitate
      thrombophlebitis and formation of DVT that may be exacerbated by the
      immobilisation of prolonged air travel. In the healthy flying population,
      immobilisation factors associated with prolonged (>5 hours) C-RD such as total
      body dehydration, hypovolaemia and increased blood viscosity, and reduced venous
      blood flow (pooling) in the legs may facilitate formation of DVT. However, data
      from at least four case-controlled epidemiological studies did not confirm a
      direct causative relationship between air travel and DVT, but factors such as a
      history of vascular thromboemboli, venous insufficiency, chronic heart failure,
      obesity, immobile standing position, more than three pregnancies, infectious
      disease, long-distance travel, muscular trauma and violent physical effort were
      significantly more frequent in DVT patients than in controls. Thus, there is no
      clear, direct evidence yet that prolonged sitting in airliner seats, or prolonged
      experimental chair-rest or bed-rest deconditioning treatments cause DVT in
      healthy people.

PMID- 15456348
TI  - Exercise for health for early postmenopausal women: a systematic review of
      randomised controlled trials.
AB  - Women who pass menopause face many changes that may lead to loss of health
      related fitness (HRF), especially if sedentary. Many exercise recommendations are
      also relevant for early postmenopausal women; however, these may not meet their
      specific needs because the recommendations are based mainly on studies on men. We
      conducted a systematic review for randomised, controlled exercise trials on
      postmenopausal women (aged 50 to 65 years) on components of HRF. HRF consists of
      morphological fitness (body composition and bone strength), musculoskeletal
      fitness (muscle strength and endurance, flexibility), motor fitness (postural
      control), cardiorespiratory fitness (maximal aerobic power, blood pressure) and
      metabolic fitness (lipid and carbohydrate metabolism). The outcome variables
      chosen were: bodyweight; proportion of body fat of total bodyweight (F%); bone
      mineral density (BMD); bone mineral content (BMC); various tests on muscle
      performance, flexibility, balance and coordination; maximal oxygen consumption (V
      dotO(2max)); resting blood pressure (BP); total cholesterol (TC); high-density
      lipoprotein-cholesterol; low-density lipoprotein-cholesterol; triglycerides;
      blood glucose and insulin. The feasibility of the exercise programme was assessed
      from drop-out, attendance and injury rates. Twenty-eight randomised controlled
      trials with 2646 participants were assessed. In total, 18 studies reported on the
      effects of exercise on bodyweight and F%, 16 on BMD or BMC, 11 on muscular
      strength or endurance, five on flexibility, six on balance or coordination, 18 on
      V-dotO(2max), seven on BP, nine on lipids and two studies on glucose an one on
      insulin. Based on these studies, early postmenopausal women could benefit from 30
      minutes of daily moderate walking in one to three bouts combined with a
      resistance training programme twice a week. For a sedentary person, walking is
      feasible and can be incorporated into everyday life. A feasible way to start
      resistance training is to perform eight to ten repetitions of eight to ten
      exercises for major muscle groups starting with 40% of one repetition maximum.
      Resistance training initially requires professional instruction, but can
      thereafter be performed at home with little or no equipment as an alternative for
      a gym with weight machines. Warm-up and cool-down with stretching should be a
      part of every exercise session. The training described above is likely to
      preserve normal bodyweight, or combined with a weight-reducing diet, preserve BMD
      and increase muscle strength. Based on limited evidence, such exercise might also
      improve flexibility, balance and coordination, decrease hypertension and improve
      dyslipidaemia.

PMID- 15456349
TI  - In vitro antifungal activities of anidulafungin and micafungin, licensed agents
      and the investigational triazole posaconazole as determined by NCCLS methods for
      12,052 fungal isolates: review of the literature.
AB  - The echinocandins anidulafungin and micafungin and the triazole posaconazole are
      currently undergoing phase III clinical trials. Caspofungin and voriconazole have
      recently been licensed for the treatment of aspergillosis (both agents), other
      less common mould (voriconazole) and candidal (caspofungin) infections. This
      review summarizes the published in vitro data obtained by NCCLS or NCCLS modified
      methods on the in vitro fungistatic and fungicidal activities of these five
      agents for yeasts and moulds in comparison to the established agents,
      amphotericin B, fluconazole, itraconazole, and flucytosine. Among the yeasts, the
      echinocandins have less activity for Candida parapsilosis and Candida
      guilliermondii, no activity for Cryptococcus neoformans and Trichosporon spp.,
      but good fungistatic and fungicidal activity in vivo and in vitro for most of the
      other Candida spp.; this fungicidal activity has been reported by minimum
      fungicidal concentrations (MFCs) or time kill curve results. The new triazoles
      exhibit good fungistatic activity (but not fungicidal) for most Candida spp., C.
      neoformans, and Trichosporon spp. For the Aspergillus spp. evaluated, the
      echinocandins have similar or better fungistatic activity than those of
      amphotericin B and the triazoles, but fungicidal activity has been demonstrated
      only with amphotericin B and the triazoles, with the exception of fluconazole.
      Most studies showed posaconazole and voriconazole minimum inhibitory
      concentrations (MICs) ranging from 0.25 to 8 microg/ml for non-solani Fusarium
      spp., while MIC and minimum effective concentration (MEC) endpoints of the
      echinocandins were >8 microg/ml. The fungistatic activity of the triazoles is
      also superior to that of the echinocandins for most of the dimorphic fungi and
      the Zygomycetes. However, micafungin has activity for the mould phase of most
      dimorphic fungi, but not for the parasitic or yeast phase of Paracoccidioides
      brasiliensis. The echinocandins appear to have variable and species dependent
      fungistatic activity for the dematiaceous fungi, but all agents have poor or no
      activity against most isolates of Scedosporium prolificans. Only amphotericin B
      exhibit good fungistatic activity against the Zygomycetes. The combination of
      caspofungin with some triazoles, amphotericin B or liposomal amphotericin B has
      been synergistic in vitro, in animal models and in patients. Breakpoints are not
      available for any mould and antifungal agent combination. In vitro/in vivo
      correlations should aid in the interpretation of these results, but standard
      testing conditions are needed for the echinocandins, especially for mould
      testing, to obtain reliable results.

PMID- 15456350
TI  - Distribution of Candida species in different clinical sources in Delhi, India,
      and proteinase and phospholipase activity of Candida albicans isolates.
AB  - Eighty-five isolates of Candida recovered from three hundred and fifty diverse
      clinical sources, viz. respiratory tract (sputum, bronchial
      washing,bronchoalveolar lavage, tracheal aspirate), blood, urine, high vaginal
      swab, skin and plastic devices, were studied in detail for their morphological
      and biochemical characters. Seven species of Candida were identified, viz., C.
      albicans (45.8%), C. tropicalis (24.7%), C. parapsilosis (10.5%), C. krusei
      (7.0%), C. kefyr (7.0%), C. guilliermondii (3.5%), and C. glabrata (1.1%). C.
      albicans was the predominant species isolated from all clinical specimens, except
      blood from which C. krusei was most frequently (38.4%) recovered. Out of 39
      isolates of C. albicans, 26 (66.6%) and 19 (48.7%) exhibited strong proteinase
      and phospholipase activity respectively. There was a higher prevalence of
      proteinase producing strains amongst the vaginal and skin isolates than that in
      urinary and respiratory isolates. Also a greater number of phospholipase
      producing strains was observed in the vaginal and urinary isolates than that in
      the respiratory and skin isolates.

PMID- 15456347
TI  - Exercise recommendations for individuals with spinal cord injury.
AB  - Persons with spinal cord injury (SCI) exhibit deficits in volitional motor
      control and sensation that limit not only the performance of daily tasks but also
      the overall activity level of these persons. This population has been
      characterised as extremely sedentary with an increased incidence of secondary
      complications including diabetes mellitus, hypertension and atherogenic lipid
      profiles. As the daily lifestyle of the average person with SCI is without
      adequate stress for conditioning purposes, structured exercise activities must be
      added to the regular schedule if the individual is to reduce the likelihood of
      secondary complications and/or to enhance their physical capacity. The acute
      exercise responses and the capacity for exercise conditioning are directly
      related to the level and completeness of the spinal lesion. Appropriate exercise
      testing and training of persons with SCI should be based on the individual's
      exercise capacity as determined by accurate assessment of the spinal lesion. The
      standard means of classification of SCI is by application of the International
      Standards for Classification of Spinal Cord Injury, written by the Neurological
      Standards Committee of the American Spinal Injury Association. Individuals with
      complete spinal injuries at or above the fourth thoracic level generally exhibit
      dramatically diminished cardiac acceleration with maximal heart rates less than
      130 beats/min. The work capacity of these persons will be limited by reductions
      in cardiac output and circulation to the exercising musculature. Persons with
      complete spinal lesions below the T(10) level will generally display injuries to
      the lower motor neurons within the lower extremities and, therefore, will not
      retain the capacity for neuromuscular activation by means of electrical
      stimulation. Persons with paraplegia also exhibit reduced exercise capacity and
      increased heart rate responses (compared with the non-disabled), which have been
      associated with circulatory limitations within the paralysed tissues. The
      recommendations for endurance and strength training in persons with SCI do not
      vary dramatically from the advice offered to the general population. Systems of
      functional electrical stimulation activate muscular contractions within the
      paralysed muscles of some persons with SCI. Coordinated patterns of stimulation
      allows purposeful exercise movements including recumbent cycling, rowing and
      upright ambulation. Exercise activity in persons with SCI is not without risks,
      with increased risks related to systemic dysfunction following the spinal injury.
      These individuals may exhibit an autonomic dysreflexia, significantly reduced
      bone density below the spinal lesion, joint contractures and/or thermal
      dysregulation. Persons with SCI can benefit greatly by participation in exercise
      activities, but those benefits can be enhanced and the relative risks may be
      reduced with accurate classification of the spinal injury.

PMID- 15456351
TI  - [Species of Malassezia associated with various dermatoses and healthy skin in the
      Mexican population].
AB  - At the present, eight Malassezia species have been described and their
      distribution in normal skin and in several skin diseases appears variable. The
      aim of the present study was to determine the frequency and distribution of
      Malassezia species in patients with psoriasis, seborrhoeic dermatitis and
      pityriasis versicolor attended in a Hospital from Mexico City, in addition to a
      healthy individual group. Scales of abnormal and healthy skin were grown in
      modified Dixon agar and the species identification was performed by macroscopic
      and microscopic features; by catalase and urease reaction; growth at 32, 37 and
      40 degrees C; and Tween 20, 40, 60 and 80 assimilation. The cultures from 63
      persons were included: forty six patients (20 psoriasis, 15 seborrhoeic
      dermatitis, 11 pityriasis versicolor) and 17 healthy individuals (external
      auditory canal). A total of 96 isolates were obtained. The more frequently
      isolated species were: M. sympodialis (38.2%) and M. furfur (26.5%) in psoriasis;
      M. sympodialis (38.5%) and M. slooffiae (34.6%) in seborrhoeic dermatitis; M.
      globosa (46.7%) and M. sympodialis (26.7%) in pityriasis versicolor; and M.
      restricta (47.6%) and M. globosa (23.8%) in normal skin. The number of isolates,
      the species diversity and association were higher in the patients group than in
      the healthy individuals group.

PMID- 15456352
TI  - [Dermatophyte infection and colonization in dogs from South Santiago, Chile].
AB  - Our main aim was to determine the dermatophyte infection and colonization
      prevalence in canines from South Santiago, Chile. We studied 241 dogs, 121 of
      them presented cutaneous lesions suggestive of dermatophytosis and the other 120
      were free from lesions and were considered clinically healthy. Dermatophytes were
      isolated from the lesions of 48.8% of animals with cutaneous diseases and from 5%
      of healthy dogs. Microsporum canis was the principal species isolated with a
      frequency of 98.3% from dermatophytosis and from all healthy carriers. The direct
      microscopic test showed a sensibility of 85% with a positive and negative
      predictive value of 74 and 79%, respectively. The highest prevalence of
      dermatophytosis were detected in animals up to one year old (p <= 0.05) and in
      dogs with high level of irritation, scaly skin, itching and alopecia (p < or =
      0.05). The lesions were detected more frequently in head-neck and anterior
      members (p < or = 0.05). This study shows some clinical characteristics and a
      frequency of dermatophytes in canines that can be interesting for laboratory
      professionals and veterinarians.

PMID- 15456353
TI  - Effect of medium components and time of cultivation on chitin production by Mucor
      circinelloides (Mucor javanicus IFO 4570) -- a factorial study.
AB  - Chitin production of mycelia from Mucor circinelloides (Mucor javanicus) was
      studied with a two-level factorial design in all combinations of the following
      factors in the culture medium: time of cultivation, concentration of D-glucose, L
      asparagine and thiamine. Chitin was characterised by infrared and nuclear
      magnetic resonance spectroscopy. The four factors showed statistically
      significant (95%) positive main effects on chitin production, without
      interactions between them. The highest chitin yield (23.9%) was obtained with the
      medium containing 60 g/l of glucose, 3 g/l of asparagine and 0.008 mg/l of
      thiamine and is comparable to the highest in the literature.

PMID- 15456354
TI  - [Effect of water activity and temperature on competing abilities of Penicillium
      oxalicum against Fusarium oxysporum].
AB  - The in vitro effect of water activity (0.995, 0.98, 0.95, 0.90 and 0.85) and
      temperature (25 and 15 degrees C) on competing abilities of the biocontrol agent
      Penicillium oxalicum against Fusarium oxysporum fsp. lycopersici, a tomato
      pathogen, and Fusarium oxysporum fsp. gladioli, a gladiolus pathogen, was
      evaluated. The aim of this study was to assess the suitability of P. oxalicum to
      be applied as a biocontrol agent against these phytopathogenic fungi. Plates were
      inoculated in two points with P. oxalicum and one of the Fusarium species. Two
      different approaches were taken into account: the growth rate of each isolate and
      the Dominance Index (ID). P. oxalicum showed higher growth rates under most of
      the conditions tested except for 0.995 aw at both temperatures and at 0.98 and 15
      degrees C. Similarly, P. oxalicum was dominating at 25 degrees C and < or = 0.95
      aw, and at 15 degrees C and < or = 0.90 aw, while under the other conditions
      studied, mutual inhibition situations were found. This indicates a high ability
      of this species to successfully compete over a wide range of conditions and
      consequently the potential of P. oxalicum as a biocontrol agent against these
      Fusarium species.

PMID- 15456355
TI  - [In vitro effect of carbohydrates and enteric bacteria on adherence of Candida
      albicans].
AB  - The adherence of Candida albicans to any cell is considered essential in the
      process that leads to colonization. Our objective in this study was to evaluate
      the effect of different carbohydrates and the presence of lactobacilli and
      Escherichia coli on the in vitro adherence of Candida albicans. The adherence to
      buccal epithelial cells was higher when growing at concentrations of galactose of
      50, and 200 mM, as well as 50, 200, and 500 mM of sucrose, and 500 mM of mannose,
      compared with that obtained when growing in Sabouraud dextrose broth (p < 0.01).
      The presence of other microorganisms, such as Lactobacillus acidophilus and L.
      casei, caused a decrease in the in vitro adherence of C. albicans to buccal
      epithelial cells (p < 0.05), whereas E. coli did not modify this adherence at
      all.

PMID- 15456356
TI  - [Treatment of coloured industrial effluents with Pleurotus spp].
AB  - The decolouration of fermentation residues (vinasse) and liquid extract of coffee
      pulp by the mushroom Pleurotus ostreatus was studied in addition to laccase
      activity. The fungus was inhibited in both residues when they remained undiluted.
      In submerged cultivation on wastewaters a good production of biomass (14.8 g/l
      for vinasse and 5.4 g/l for extract of coffee pulp) and also laccase activity
      (14.1 U/ml for vinasse and 3.0 U/ml for extract of coffee pulp) up to the 10 days
      of fermentation was observed, being significantly greater in the culture with
      vinasse. It was shown that treatment with this mushroom reduces both the chemical
      oxygen demand and the colour, contributing to their biological treatment.

PMID- 15456357
TI  - [Canine onychomycosis produced by Microsporum gypseum. A case report].
AB  - One case of severe canine onychomycosis is described. The aetiological agent was
      identified as Microsporum gypseum. The incidence of this fungus in this kind of
      pathology is discussed, with special attention to the successful treatment with
      topic enilconazole and systemic griseofulvin.

PMID- 15456358
TI  - [A survey of temperature and pH effect on colonial growth of Botryodiplodia
      theobromae RC1].
AB  - Study of fungal colonial growth is a basic method to examine their behaviour in
      different cultivation conditions. The influence of temperature and initial pH on
      growth radial velocity and growth density of Botryodiplodia theobromae RC1, was
      studied in order to show the growth characteristics of this fungus. Both
      temperature and culture medium influenced growth density, but radial velocity of
      growth was only affected by temperatures above 40 degrees C. In addition, initial
      pH of culture media did not affect either parameter.

PMID- 15456359
TI  - [Combined effect of copper and initial pH of the culture on production of laccase
      and manganese peroxidase by Stereum hirsutum (Willd) Pers].
AB  - Stereum hirsutum is a white-rot fungus which produces laccase and manganese
      peroxidase as part of its ligninolytic system. Maximal ligninases production
      (under the conditions studied) was obtained in the media containing 250 microM
      Cu++ along with a pH value of 5.5. The fitting of ligninase production to a
      linear equation showed negative interaction between increasing values of pH and
      concentration of copper.

PMID- 15456360
TI  - [Clinical cases in Medical Mycology].

PMID- 15456361
TI  - [First local case of human cryptococcosis in Spain caused by Cryptococcus
      neoformans var. gattii].

PMID- 15456362
TI  - [Invasive aspergillosis].
AB  - Invasive aspergillosis is one of the most frequent fungal infections in
      neutropenic patients, in whom it is associated with a high mortality. Its
      diagnosis is difficult by the traditionally used laboratory tests. In the last
      years, an ELISA (Platelia Aspergillus, Bio-Rad, France) to detect galactomannan
      in neutropenic and cancer patients with high risk of suffering invasive
      aspergillosis has been developed. The experience accumulated in Spain in the
      diagnosis of invasive aspergillosis by Platelia Aspergillus is presented in this
      monograph.

PMID- 15456363
TI  - [Invasive aspergillosis: clinical manifestations and treatment].
AB  - During the last decade the incidence of invasive aspergillosis has substantially
      grown due to the increasing use of powerful immunosupressive drugs in more
      patients. Unfortunately, the associated mortality with this infection is still
      very high and has not decreased in recent years. Pulmonary aspergillosis is by
      far the most frequent clinical picture of this infection, followed by sinus,
      tracheo-bronchial and central nervous system disease. The degree of
      immunosupression is the main factor influencing the evolution and dissemination
      of aspergillosis. Conventional amphotericin B has been the first-line therapy of
      invasive aspergillosis for the last 30 years, and most authors have long
      considered amphotericin B related toxicity as one of the main causes for the poor
      results obtained in the outcome of patients who developed this infection.
      Fortunately, in the last few years new safer and more effective drugs have been
      developed for the treatment of this entity. However, if we are really trying to
      substantially decrease invasive aspergillosis associated-mortality we should use
      these drugs earlier in the development of the infection, using new more sensitive
      diagnostic tests and/or a riskbase strategy which could identify patients at the
      highest risk to develop this infection.

PMID- 15456364
TI  - [Laboratory diagnosis of invasive aspergillosis].
AB  - Invasive aspergillosis is major cause of morbility and mortality in
      immunosuppressed patients, in part due to the inability to identify infected
      patients at an early stage of the disease. Diagnosis is based on a combination of
      imaging (high-resolution computed tomography) and a number of laboratory
      techniques including direct examination, culture and circulating markers
      (galactomannan and Aspergillus DNA) which can be detected at early stages of the
      infection.

PMID- 15456365
TI  - [Early diagnosis of invasive aspergillosis in neutropenic patients with bi-weekly
      serial screening of circulating galactomannan by Platelia Aspergillus].
AB  - The diagnosis of invasive aspergillosis in neutropenic individuals is difficult
      and lengthy since non-invasive diagnostic tests lack sensitivity and specificity.
      The diagnosis of invasive aspergillosis in 154 prolonged neutropenic patients was
      prospectively bi-weekly validated by screening circulating galactomannan. The
      global sensitivity was 73% and specificity was 96%. The positive and negative
      predictive values were 73% and 98% respectively. False positive reactions
      occurred at a rate of 2%. Antigenemia was detected before clinical suspicion of
      invasive aspergillosis (median, 6 days before) in 30% of patients and anticipated
      the onset of radiologic signs 9 days in 60% of patients. CONCLUSION: the
      prospective screening of galactomannan is a sensitive and non-invasive tool for
      early diagnosis of invasive aspergillosis in high-risk adult hematology patients.

PMID- 15456366
TI  - [Usefulness of galactomannan detection in the diagnosis and follow-up of
      hematological patients with invasive aspergillosis].
AB  - The usefulness of galactomannan detection using the Platelia Aspergillus test for
      the diagnosis of invasive aspergillosis was studied in 849 sera from 54
      hematological patients with prolonged neutropenia, which were classified
      according to the risk for invasive aspergillosis. Three patients developed a
      proven invasive aspergillosis, one a probable invasive aspergillosis and 17
      patients a possible invasive aspergillosis. Thirty-three patients showed no
      evidence of invasive aspergillosis. All patients with proven invasive
      aspergillosis had a high risk for invasive aspergillosis, while the one having
      probable invasive aspergillosis had intermediate risk. Detection of galactomannan
      in this study showed a sensitivity of 66.7% for patients with proven invasive
      aspergillosis and 50% for patients with proven and probable invasive
      aspergillosis. The specificity was 98% or higher in all groups studied. The
      predictive positive and negative values for patients with proven invasive
      aspergillosis were 66.7% and 98%, respectively. A rise in the concentration of
      galactomannan was observed in patients who failed to respond to the antifungal
      treatment. Galactomannan antigenemia preceded post-mortem histological diagnosis
      of invasive aspergillosis in two patients by 17 and 81 days, respectively. In
      conclusion, detection of galactomannan by the Platelia Aspergillus test allows
      for a specific and relatively sensitive diagnosis of invasive aspergillosis in
      hematological patients with a high and intermediate risk for invasive
      aspergillosis.

PMID- 15456367
TI  - [Aspergillus galactomannan detection in allogenic hematopoietic cell
      transplantation].
AB  - Invasive aspergillosis has become the leading cause of death after allogeneic
      hematopoietic stem cell transplantation. This is partially due to the lack of a
      prompt diagnosis. Recently the detection of Aspergillus galactomannan antigen by
      means an ELISA technique in serum has been described. The objective of this study
      was to validate its usefulness in the allogeneic hematopoietic stem cell
      transplantation setting.

PMID- 15456368
TI  - [Value of Aspergillus galactomannan antigen detection in the diagnosis and follow
      up of invasive aspergillosis in hematological patients].
AB  - Serum galactomannan detection is considered to be a useful test for early
      diagnosis and follow-up of invasive aspergillosis. From February to September
      2002, adult patients hospitalized in our Hematology Unit for receiving intensive
      chemotherapy and/or hematopoietic stem cell transplant were prospectively
      studied. We analyzed a total of 760 samples obtained from 100 patients. Eleven
      patients (11%) having a positive result (OD index >1.5 ng/ml) in two consecutive
      Platelia Aspergillus tests were considered galactomannan-positive cases. On the
      other hand, 12 patients (12%) were diagnosed of proven or probable invasive
      aspergillosis. Sensitivity (66.6%), specificity (95.5%), positive predictive
      value (72.7%) and negative predictive value (96.7%) were comparable to those of
      larger series. Galactomannan positivity allowed also to anticipate invasive
      aspergillosis diagnosis (from two to 17 days before radiographic findings and
      from two to 15 days before mycological culture). Moreover, kinetics of
      antigenemia could be useful for assessing therapeutic response. Once accepted
      galactomannan test as a diagnostic criterium for invasive aspergillosis knowing
      potential causes of false positive results is of paramount importance.

PMID- 15456369
TI  - [Yeast carriage on the hands of Medicine students].
AB  - The main focus of our study was to determine the prevalence of yeasts on the
      hands of Medicine students and other students not related to the Health care
      system. Between July 1999 and July 2000, 253 students of Medicine (163) and
      Engineering (90) were studied. Medicine students were grouped as basic (71), pre
      clinical (62) and clinical (30). The Engineering's students were divided into
      three groups according to the years of study. The total yeasts carried on the
      hands of Medicine's students were 16%. By group the results were 7% for the
      basic, 19% for the pre-clinical and 30% for the clinical and the prevalence of
      the two last groups was higher than the first one. The Engineering's students
      showed 9% prevalence without differences between years of career. The yeast
      carriage in the clinical group was higher than the equivalent control group
      (10%). The species frequently encountered were Rhodotorula mucilaginosa
      (Rhodotorula rubra) and Candida parapsilosis, with a tendency to a higher species
      diversity and colony count in the pre-clinical and clinical groups. This finding
      could explain the high prevalence of candidemia by C. parapsilosis in our
      hospitals. In summary, yeast carriage, diversity and quantity in Medicine
      students were related to the time of being in the hospital environment.

PMID- 15456370
TI  - [Prevalence of Candida albican serotypes in blood isolates in Chile, and first
      report of Candida dubliniensis candidemia].
AB  - Our main goal was to determine the prevalence of C. albicans serotypes isolates
      from blood cultures and identify the presence of C. dubliniensis. We studied 47
      strains identified as C. albicans by conventional methods, 28 were isolated from
      children and 19 from adult patients. The strains were re-identified by standard
      methods and phenotypic screening as xylose assimilation and growth at 42 degrees
      C. API ID 32C (bioMerieux) was employed with the C. dubliniensis suspected
      strains and confirmation was made by molecular fingerprinting using random
      amplified polymorphic DNA (RAPD). The C. albicans serotype was determined by
      agglutination with antiserum anti-antigen 6 from cell wall (Candida Check, Iatron
      Inc., Japan) and the in vitro susceptibilities were evaluated by a microdilution
      method. From 47 strains, 46 were confirmed as C. albicans, 31 of them (67%) were
      serotype A. Adult patients presented a high prevalence of serotype A (95%) and
      children presented a frequency of 52% of the serotype B (p<0.05). We confirmed
      the identification of C. dubliniensis in one strain isolated from an infant. All
      serotype B strains were susceptible to fluconazole, itraconazole and amphotericin
      B. On the other hand, 3% and 6% of serotype A strains were "susceptible dose
      dependent" to fluconazole and itraconazole, respectively. C. albicans serotype A
      was predominant in adult candidemia and its distribution was homogenous in
      children patients. All strains were highly susceptible to antifungals. We report
      here the first case of C. dubliniensis candidemia in South America.

PMID- 15456371
TI  - Adherence of Candida albicans and Candida dubliniensis to buccal and vaginal
      cells.
AB  - Twenty-seven Candida albicans strains and 26 Candida dubliniensis strains,
      isolated from HIV patients, were tested for their adherence to buccal and vaginal
      epithelial cells. Both species showed important levels of adhesion to buccal and
      vaginal epithelial cells, although C. albicans showed the highest levels of
      adhesion. These results suggest that both Candida species are well adapted, in
      terms of adhesion capability, to the oral and vaginal environment.

PMID- 15456372
TI  - Comparative experimental infection of Lacazia loboi in BALB/c and B10.A mice.
AB  - Both hind foot pads of BALB/c and B10.A mice strains, were inoculated with a
      fungal suspension of Lacazia loboi obtained from a Jorge Lobo's disease patient.
      The suspension had 9 x 105 cells/ml and its viability index was 45%. The animals
      were sacrificed at different time periods varying from 24 h to 18 months after
      inoculation. The BALB/c mice developed an extensive granulomatous infiltrate,
      similar to the disease in humans, that progressively evolved. The number of
      fungal elements also increased as the disease progressed, and after the seventh
      month of inoculation, macroscopic changes of the foot pads were evident. Although
      the B10.A mice developed an exuberant granulomatous infiltrate, macroscopic
      changes were not detected. The number of fungal cells in the infected tissues
      increased in number, but they were lower then the numbers found in the BALB/c
      strain. The viability indexes were also lower for the B10.A strain. Considering
      the histopathological findings, the presence of macroscopic changes and the great
      amount of fungal cells in the infected tissues, the authors concluded that the
      BALB/c mice strain was more susceptible to L. loboi infection than the B10.A
      strain.

PMID- 15456373
TI  - The distribution frequency of Candida species in the genitourinary tract among
      symptomatic individuals in Nigerian cities.
AB  - A clinical survey was carried out in seven cities in the southern part of Nigeria
      to determine the relative distribution of genitourinary Candida species in
      symptomatic patients reporting for diagnosis and treatment. Seven Candida species
      were identified using the CHROMagar Candida method and the API 20C System.
      Candida species were represented by Candida glabrata (33.7%), Candida albicans
      (20.1%), Candida tropicalis (18%), Candida guilliermondii (17.8%) Candida
      pseudotropicalis (5%), Candida parapsilosis (5%), and C. albicans
      var.stellatoidea (1.2%). The distribution of these species among the various age
      groups (15-20, 21-25, 26-30, 31-35, 36-40 and 41 plus years) was statistically
      insignificant. Out of the 517 positive samples, 182 (35%) were found in the age
      group 26-30 years, while age 41 plus had the lowest frequency (1.2%). The results
      presented show that C. albicans, usually reported to be the most frequently
      isolated species, is not the main species in the cities studied. With C. glabrata
      in preponderance, the finding supports recent studies reporting that several
      pathogenic non-C. albicans species are now being frequently isolated. The level
      of social activities, such as drug abuse and sexual promiscuity, may be important
      in the distribution frequency of Candida species in different age groups and
      locations.

PMID- 15456374
TI  - [Successful treatment with voriconazol of a Pseudallescheria boydii fungus ball
      in a HIV positive patient and previous tuberculosis].
AB  - We herein describe a patient with a Pseudallescheria boydii fungus ball in a
      tuberculous lung cavity, which was successfully treated four years earlier. The
      patient was HIV positive classified as C3 with a previous history of i.v. heroin
      abuse. The clinical presumptive diagnosis was radiologically established combined
      with histological examination. Culture of tissue confirmed and proved the fungal
      etiology. In vitro MIC values for voriconazole (0.5 mg/ml) guided antifungal
      prophylactic treatment before surgical eradication of the fungus ball since the
      patient was immunosuppressed. We discuss the clinical spectrum of P. boydii
      infections and currently medical approach.

PMID- 15456375
TI  - Scedosporium apiospermum keratitis.
AB  - A case of Scedosporium apiospermum keratitis is reported in a 65-year-old farmer
      referred for treatment of an extensive corneal ulcer in the left eye. Direct
      examination of scrapes revealed abundant filamentous septate hyphae; all cultures
      were consistently positive for the same fungus, identified later as Scedosporium
      apiospermum. The patient successfully responded to treatment with amphotericin B.

PMID- 15456376
TI  - [Clinical cases in Medical Mycology].

PMID- 15456377
TI  - [Clinical cases in Medical Mycology].

PMID- 15456378
TI  - Validation of idiosyncratic cognitive schema in cognitive case formulations: an
      intraindividual idiographic approach.
AB  - This article describes a method for the intraindividual clinical validation of a
      cognitive case formulation (CCF) involving hypotheses about the patient's
      idiosyncratic cognitive schema (ICS). The two-stage approach begins by testing
      the convergent and discriminant validity of the hypothesized ICS against the
      individual's daily ratings of cognition items using confirmatory dynamic factor
      analysis. The second stage evaluates the extent to which the ICS factor scores
      predict daily variability in symptoms and distress and further addresses
      convergent and discriminant validity by evaluating intraindividual cognitive
      content specificity and the incremental validity of the idiographic cognition
      factors compared with nomothetic measures of thoughts/beliefs. This approach to
      validating idiographic assessment is illustrated with the CCF of a woman with
      comorbid mood and anxiety disorders.

PMID- 15456379
TI  - Focus groups in psychological assessment: enhancing content validity by
      consulting members of the target population.
AB  - A review of articles in Psychological Assessment reveals that many researchers
      develop instruments without the benefit of consultation with members of the
      target population. To the extent that researchers do consult the target
      population, most fail to bring consultation in early enough to inform the
      identification and specification of key constructs. Moreover, this consultation
      typically takes the form of one-to-one interviews. The authors' goal in this
      article was to elaborate on the importance of population consultation as part of
      content validation and to critically evaluate the potential of one method of
      consultation, focus groups, to inform multiple stages of instrument development.
      The authors suggest that this method holds promise for enhancing the content
      validity of instruments and, ultimately, the validity of research findings.

PMID- 15456380
TI  - Psychometric evaluation of the behavioral inhibition/behavioral activation scales
      in a large sample of outpatients with anxiety and mood disorders.
AB  - The latent structure, reliability, and validity of the Behavioral
      Inhibition/Behavioral Activation Scales (BIS/BAS; C. L. Carver and T. L. White,
      1994) were examined in a large sample of outpatients (N = 1,825) with anxiety and
      mood disorders. Four subsamples were used for exploratory and confirmatory factor
      analyses. In addition to generally upholding a latent structure found previously
      in nonclinical samples, results indicated measurement invariance of the BIS/BAS
      between genders and a higher order structure of the BAS scales. Convergent and
      discriminant validity of the BIS/BAS were supported by findings that the
      subscales correlated most strongly with measures of neighboring personality
      constructs (e.g., BIS with neuroticism, BAS with positive affect) than with
      measures of current anxiety and depression symptoms. Overall, the results support
      the psychometric properties of the BIS/BAS in this clinical sample.

PMID- 15456381
TI  - Construct validity of the posttraumatic stress disorder checklist in cancer
      survivors: analyses based on two samples.
AB  - The measurement of posttraumatic stress disorder (PTSD) is critically important
      for the identification and treatment of this disorder. The PTSD Checklist (PCL;
      F. W. Weathers and J. Ford, 1996) is a self-report measure that is increasingly
      used. In this study, the authors investigated the factorial validity of the PCL
      with data from 236 cancer survivors who received a bone marrow or stem cell
      transplantation. The authors examined the fit of these data with the clinical
      model of 3 symptom clusters for PTSD, as proposed in the Diagnostic and
      Statistical Manual of Mental Disorders, and alternative models tested in prior
      research. By using confirmatory factor analysis the authors found that a 4-first
      order-factor model of PTSD provided the best fit. The relations of PTSD symptoms
      with sociodemographic and medical variables were also explored.

PMID- 15456382
TI  - A brief actuarial assessment for the prediction of wife assault recidivism: the
      Ontario domestic assault risk assessment.
AB  - An actuarial assessment to predict male-to-female marital violence was
      constructed from a pool of potential predictors in a sample of 589 offenders
      identified in police records and followed up for an average of almost 5 years.
      Archival information in several domains (offender characteristics, domestic
      violence history, nondomestic criminal history, relationship characteristics,
      victim characteristics, index offense) and recidivism were subjected to setwise
      and stepwise logistic regression. The resulting 13-item scale, the Ontario
      Domestic Assault Risk Assessment (ODARA), showed a large effect size in
      predicting new assaults against legal or common-law wives or ex-wives (Cohen's d
      = 1.1, relative operating characteristic area =.77) and was associated with
      number and severity of new assaults and time until recidivism. Cross-validation
      and comparisons with other instruments are also reported.

PMID- 15456383
TI  - Identifying psychopathy subtypes on the basis of personality structure.
AB  - The authors used model-based cluster analysis to identify subtypes of criminal
      psychopaths on the basis of differences in personality structure. Participants
      included 96 male prisoners diagnosed as psychopathic, using the Psychopathy
      Checklist Revised (PCL-R; R. D. Hare, 1991). Personality was assessed using the
      brief form of the Multidimensional Personality Questionnaire (MPQ-BF; C. J.
      Patrick, J. J. Curtin, and A. Tellegen, 2002). The best-fitting model yielded two
      clusters. Emotionally stable psychopaths were characterized by low Stress
      Reaction and high Agency. Aggressive psychopaths were characterized by high
      Negative Emotionality, low Constraint, and low Communion. These results suggest
      that psychopaths as defined by the PCL-R includes distinct subtypes,
      distinguishable in terms of personality structure, that may reflect different
      etiologies.

PMID- 15456384
TI  - Psychometric Properties of the Posttraumatic Cognitions Inventory (PTCI): a
      replication with motor vehicle accident survivors.
AB  - This study examined the factor structure, internal consistency, concurrent
      validity, discriminant validity, and discriminative validity of the Posttraumatic
      Cognitions Inventory (PTCI; E. B. Foa, A. Ehlers, D. M. Clark, D. F. Tolin, and
      S. M. Orsillo, 1999) in a sample of 112 individuals who had experienced a serious
      motor vehicle accident. Results generally supported the 3-factor structure of the
      PTCI: (a) Negative Cognitions About Self, (b) Negative Cognitions About the
      World, and (c) Self-Blame. Subscales reflecting negative thoughts of the self and
      world showed adequate internal consistency, as well as good concurrent,
      discriminant, and discriminative validity. However, difficulties with the
      subscale representing self-blame emerged, specifically poor concurrent and
      discriminant validity. Potential reasons for this finding are discussed. The PTCI
      seems to be a promising measure of negative and dysfunctional posttrauma
      cognitions, which deserves continuing attention.

PMID- 15456385
TI  - A depressive symptom scale for the California Psychological Inventory: construct
      validation of the CPI-D.
AB  - To facilitate life span research on depressive symptomatology, a depressive
      symptom scale for the California Psychological Inventory (CPI) is needed. The
      authors constructed such a scale (the CPI-D) and compared its psychometric
      properties with 2 widely used self-report depression scales: the Beck Depression
      Inventory and the Center for Epidemiological Studies Depression Scale. Construct
      validity of the CPI-D was examined in 3 studies. Study 1 established content
      validity, classifying CPI-D items into Diagnostic and Statistical Manual of
      Mental Disorders-Fourth Edition depressive symptoms. Study 2 used 3 large samples
      to gather evidence for reliability and validity: correlational analyses
      demonstrated alpha reliability and convergent and discriminant validity; factor
      analysis provided evidence for discriminant validity with anxiety; and regression
      analyses demonstrated comparative validity with existing standard PI scales.
      Study 3 used clinician ratings of depression and anxiety as criteria for external
      validity.

PMID- 15456386
TI  - The validity of the five-factor model prototypes for personality disorders in two
      clinical samples.
AB  - The authors examined the validity of D. R. Lynam and T. A. Widiger's (2001)
      prototypes for personality disorders (PDs) derived from the facets of the 5
      factor model (FFM) of personality in 2 clinical samples. In the 1st sample (N =
      94), there was good agreement between the prototypes generated by experts and the
      profiles reported by patients. These FFM PD similarity scores also demonstrated
      good convergent and discriminant validity with results from a semistructured
      interview and a self-report measure of Axis II pathology. In the 2nd sample (N =
      132), the FFM PD similarity scores demonstrated excellent longitudinal stability
      and good predictive validity with regard to consensus ratings of PD features. The
      implications of these findings are discussed.

PMID- 15456387
TI  - Values for comparison of WAIS-III index scores with overall means.
AB  - The Wechsler Adult Intelligence Scale--Third Edition (WAIS-III; Wechsler, 1997b)
      provides factor-based index scores but allows only for pairwise comparison of
      these scores, producing inflated Type I error rates and reducing profile
      interpretability. This article provides tables for simultaneous comparison to the
      overall mean index score, thus reducing error rates and aiding interpretation.
      The Working Memory Index or Processing Speed Index can also be specifically
      compared when an individual is believed to have a condition, such as a learning
      disability or traumatic brain injury, associated with the selective depression of
      these indexes. Tables for the infrequency of specific differences are also
      provided, allowing the practitioner to note how unusual an obtained difference is
      in the general population.

PMID- 15456388
TI  - Factor validation of the addiction severity index scale structure in persons with
      concurrent disorders.
AB  - Confirmatory factor analysis was used to test the scale structure of the
      Addiction Severity Index (ASI) in a sample of 1,802 substance abusers (43%
      alcohol dependent) with a concurrent psychiatric disorder (46% with mood
      disorders). The fit of the original composite score model based on the work of P.
      L. McGahan, J. A. Griffith, R. Parente, and A. T. McLellan (1990) was compared
      with the evaluation indices (EIs) developed by A. I. Alterman et al. (1998). The
      5-dimensional model based on the EIs was an overall better fit to the data.
      Internal consistency (Cronbach's alpha) for the EIs ranged from.66 (family
      domain) to.75 (legal domain). The 5 EIs were moderately correlated (rs =.42-.72)
      with the interviewer severity ratings from the ASI. Evaluation studies involving
      concurrent disordered substance abusers should use the EIs as summary measures of
      change.

PMID- 15456389
TI  - Measuring informant discrepancies in clinical child research.
AB  - Discrepancies among informants' ratings of child psychopathology have important
      implications for diagnosis, assessment, and treatment. Typically, parents and
      children complete measures (e.g., self-report checklists, diagnostic instruments)
      to assess child dysfunction. Ratings gathered from these sources reveal
      relatively little agreement on the nature and extent of the child's social,
      emotional, and behavioral problems. This article reviews and illustrates the most
      frequently used methods of measuring informant discrepancies in the clinical
      child literature (i.e., raw difference, standardized difference, and residual
      difference scores) and outlines key considerations to influence their selection.
      The authors conclude that frequently used methods of measuring informant
      discrepancies are not interchangeable and recommend that future investigations
      examining informant discrepancies in clinical child research use the standardized
      difference score as their measure of informant discrepancies.

PMID- 15456390
TI  - Cross-national differences in the assessment of psychopathy: do they reflect
      variations in raters' perceptions of symptoms?
AB  - Cross-national differences in the prevalence of psychopathy have been reported.
      This study examined whether rater effects could account for these differences.
      Psychopathy was assessed with the Psychopathy Checklist-Revised (PCL-R; R. D.
      Hare, 1991). Videotapes of 6 Scottish prisoners and 6 Canadian prisoners were
      rated by 10 Scottish and 10 Canadian raters. No significant main or interaction
      effects involving the nationality of raters were detected at the level of full
      scores or factor scores. Using a generalizability theory approach, it was
      demonstrated that the interrater reliability of total scores was good, that is,
      the proportion of variance in test scores attributable to raters was small. The
      interrater reliability of factor scores was lower, typically falling in the fair
      range. Overall, the results suggest that the reported cross-national differences
      are more likely to be in the expression of the disorder rather than in the eye of
      the beholder.

PMID- 15456392
TI  - Mind the gap: interhemispheric communication about emotional faces.
AB  - This study tested the hypothesis that interhemispheric communication about
      emotional stimuli is influenced by situational factors that alter emotional
      relevance. Under evaluative or nonevaluative conditions, participants matched
      angry and happy faces within a single visual field or across opposite visual
      fields. An overall across-field advantage (AFA) reflected the benefit of sharing
      information between the hemispheres. The AFA was greater for angry than for happy
      faces in the evaluation condition but did not differ for angry and happy faces in
      the no-evaluation condition. Examination of individual differences indicated that
      high trait evaluation levels of worry were associated with poorer
      interhemispheric communication of angry faces, supporting a threat-avoidance
      conception of worry. Thus, both situational factors and individual differences
      affected interhemispheric communication about emotional faces.

PMID- 15456393
TI  - Snakes and cats in the flower bed: fast detection is not specific to pictures of
      fear-relevant animals.
AB  - The observation that snakes and spiders are found faster among flowers and
      mushrooms than vice versa and that this search advantage is independent of set
      size supports the notion that fear-relevant stimuli are processed preferentially
      in a dedicated fear module. Experiment 1 replicated the faster identification of
      snakes and spiders but also found a set size effect in a blocked, but not in a
      mixed-trial, sequence. Experiment 2 failed to find faster identification of snake
      and spider deviants relative to other animals among flowers and mushrooms and
      provided evidence for a search advantage for pictures of animals, irrespective of
      their fear relevance. These findings suggest that results from the present visual
      search task cannot support the notion of preferential processing of fear
      relevance.

PMID- 15456394
TI  - Developmental changes in facial expressions of emotions in the strange situation
      during the second year of life.
AB  - Infants' expressions of discrete emotions were coded during the more stressful
      episodes (4 through 8) of the Strange Situation at 13 and 18 months. The data
      showed a significant decrease in full-face expressions (more complex
      configurations of movements) and a significant increase in component expressions
      (simpler and more constrained patterns of movements). The authors interpreted
      this trend as a developmental change toward more regulated and less intense
      emotions. Consistent with this view, the aggregate index of infants' full-face
      negative emotion expressions, interpreted as reflecting relatively unregulated
      intense emotions, correlated significantly with maternal ratings of difficult
      temperament. The authors discuss alternative interpretations of the findings in
      terms of changes in reactivity/arousability and the emerging capacity for self
      regulation.

PMID- 15456395
TI  - Valence focus and the perception of facial affect.
AB  - Individuals differ in the extent to which they emphasize feelings of pleasure or
      displeasure in their verbal reports of emotional experience, an individual
      difference termed valence focus (VF). This multimethod study indicates that VF is
      linked to heightened efficiency in perceptual processing of affective stimuli.
      Individuals higher in VF (i.e., who emphasized feelings of pleasure/displeasure
      in reports of emotional experiences) were more sensitive to changes in negative
      facial expressions than individuals lower in VF. The effect was not accounted for
      by current affective state or other personality characteristics. Implications for
      the validity of self-reported experienced emotion are discussed.

PMID- 15456396
TI  - Independent manipulation of emotion in an emotional stroop task using classical
      conditioning.
AB  - The effects of emotional connotation on emotional Stroop interference in anxiety
      were examined. First, a classical conditioning paradigm was used in which neutral
      words and nonwords were paired with either negative or neutral pictures. These
      conditioned stimuli were then presented in an emotional Stroop paradigm. Finally,
      participants rated each word and nonword for emotional connotation. The high
      anxious group demonstrated significant interference for the nonwords that had
      been negatively conditioned, and these effects did not dissipate over time. The
      affective rating data supported the view that nonwords, but not the words had
      been successfully conditioned in the high-anxious group. This experiment provides
      evidence for the importance of emotional connotation rather than confounded
      semantic factors in the emotional Stroop effect.

PMID- 15456397
TI  - The influence of unilateral and bilateral arm flexion versus extension on
      judgments: an exploratory case of motor congruence.
AB  - Two experiments were conducted to examine how activation of the motivational
      systems of approach and withdrawal (arm flexion vs. extension) through 2
      different bodily mechanisms (right arm vs. left arm) influenced participants'
      evaluations of neutral Chinese ideographs. Study 1 found that unilateral flexion
      on the right side and unilateral extension on the left side led to more positive
      evaluations than unilateral flexion on the left side and unilateral extension on
      the right side. Using bilateral movements, Study 2 found that simultaneous
      performance of a right-arm flexion and a left-arm extension led to more positive
      evaluations than a left-arm flexion and a right-arm extension. A motor congruence
      hypothesis was offered to account for these findings.

PMID- 15456398
TI  - Memory of faces: a slow wave ERP study of major depression.
AB  - This study examined slow wave (SW) event-related brain potential (ERP) amplitudes
      in response to happy, neutral, and sad faces during a working memory task to
      further identify the associated component processes and physiological changes of
      mood-congruent memory biases in individuals with and without major depression.
      The results suggest that individuals with and without a diagnosis of major
      depressive disorder (MDD) differentially maintain valenced facial information in
      their working memory. Specifically, the nondepressed individuals displayed a
      marked reduction in SW amplitude to the negative faces. Individuals with MDD
      exhibited equivalent SW amplitudes for positive and negative facial stimuli.
      Results are discussed in terms of avoidance coping, previous ERP studies of
      working memory, and facial recognition deficits in individuals with MDD.

PMID- 15456399
TI  - Emotional stroop performance for masked angry faces: it's BAS, not BIS.
AB  - Theoretical models concerning selective attention to emotional stimuli predict
      heightened vigilance to angry faces in people with heightened trait anxiety or
      greater activity of the Behavioral Inhibition System (BIS). Recent evidence from
      electroencephalographic lateralization and affect studies and from studies
      assessing attentional biases to angry faces suggest, however, that heightened
      anger and activity of the Behavioral Activation System (BAS) should predict
      vigilant responding to angry faces. Social anxiety should predict avoidance of
      angry faces. Results from a masked emotional Stroop task verified these
      hypotheses, but an unmasked emotional Stroop provided no reliable relations. This
      dissociation confirms earlier claims that masked emotional Stroop performance is
      impervious to conscious control over the cognitive-emotional processes, as
      measured by the Stroop task.

PMID- 15456400
TI  - Does imminent threat capture and hold attention?
AB  - According to models of attention and emotion, threat captures and holds
      attention. In behavioral tasks, robust evidence has been found for attentional
      holding but not for attentional capture by threat. An important explanation for
      the absence of attentional capture effects is that the visual stimuli used posed
      no genuine threat. The present study investigated whether visual cues that signal
      an aversive white noise can elicit attentional capture and holding effects. Cues
      presented in an attentional task were simultaneously provided with a threat value
      through an aversive conditioning procedure. Response latencies showed that
      threatening cues captured and held attention. These results support recent views
      on attention to threat, proposing that imminent threat captures attention in
      everyone.

PMID- 15456401
TI  - A novel NADPH:(bound) NADP+ reductase and NADH:(bound) NADP+ transhydrogenase
      function in bovine liver catalase.
AB  - Many catalases have the shared property of containing bound NADPH and being
      susceptible to inactivation by their own substrate, H2O2. The presence of
      additional (unbound) NADPH effectively prevents bovine liver and human
      erythrocytic catalase from becoming compound II, the reversibly inactivated state
      of catalase, and NADP+ is known to be generated in the process. The function of
      the bound NADPH, which is tightly bound in bovine liver catalase, has been
      unknown. The present study with bovine liver catalase and [14C]NADPH and
      [14C]NADH revealed that unbound NADPH or NADH are substrates for an internal
      reductase and transhydrogenase reaction respectively; the unbound NADPH or NADH
      cause tightly bound NADP+ to become NADPH without becoming tightly bound
      themselves. This and other results provide insight into the function of tightly
      bound NADPH.

PMID- 15456402
TI  - A highly acid-stable and thermostable endo-beta-glucanase from the
      thermoacidophilic archaeon Sulfolobus solfataricus.
AB  - The thermoacidophilic archaeon Sulfolobus solfataricus P2 encodes three
      hypothetic endo-beta-glucanases, SSO1354, SSO1949 and SSO2534. We cloned and
      expressed the gene sso1949 encoding the 334 amino acids containing protein
      SSO1949, which can be classified as a member of glycoside hydrolase family 12.
      The purified recombinant enzyme hydrolyses carboxymethylcellulose as well as
      cello-oligomers, with cellobiose and cellotriose as main reaction products. By
      following the hydrolysis of a fluorescently labelled cellohexaoside under a wide
      variety of conditions, we show that SSO1949 is a unique extremophilic enzyme.
      This archaeal enzyme has a pH optimum of approx. pH 1.8 and a temperature optimum
      of approx. 80 degrees C. Furthermore, the enzyme is thermostable, with a half
      life of approx. 8 h at 80 degrees C and pH 1.8. The thermostability is strongly
      pH-dependent. At neutral pH, the thermal inactivation rate is nearly two orders
      of magnitude higher than at pH 1.8. Homology modelling suggests that the
      catalytic domain of SSO1949 has a similar fold to other mesophilic, acidophilic
      and neutral cellulases. The presence of a signal peptide indicates that SSO1949
      is a secreted protein, which enables S. solfataricus to use cellulose as an
      external carbon source. It appears that SSO1949 is perfectly adapted to the
      extreme environment in solfataric pools. A cellulolytic enzyme with such a
      combination of stability and activity at high temperatures and low pH has not
      been described so far and could be a valuable tool for the large-scale hydrolysis
      of cellulose under acidic conditions.

PMID- 15456403
TI  - Oligomeric states of the voltage-dependent anion channel and cytochrome c release
      from mitochondria.
AB  - The VDAC (voltage-dependent anion channel) plays a central role in apoptosis,
      participating in the release of apoptogenic factors including cytochrome c. The
      mechanisms by which VDAC forms a protein-conducting channel for the passage of
      cytochrome c are not clear. The present study approaches this problem by
      addressing the oligomeric status of VDAC and its role in the induction of the
      permeability transition pore and cytochrome c release. Chemical cross-linking of
      isolated mitochondria or purified VDAC with five different reagents proved that
      VDAC exists as dimers, trimers or tetramers. Fluorescence resonance energy
      transfer between fluorescently labelled VDACs supports the concept of dynamic
      VDAC oligomerization. Mitochondrial cross-linking prevented both permeability
      transition pore opening and release of cytochrome c, yet had no effect on
      electron transport or Ca2+ uptake. Bilayer-reconstituted purified cross-linked
      VDAC showed decreased conductance and voltage-independent channel activity. In
      the dithiobis(succinimidyl propionate)-cross-linked VDAC, these channel
      properties could be reverted to those of the native VDAC by cleavage of the cross
      linking. Cross-linking of VDAC reconstituted into liposomes inhibited the release
      of the proteoliposome-encapsulated cytochrome c. Moreover, encapsulated, but not
      soluble cytochrome c induced oligomerization of liposome-reconstituted VDAC. Thus
      the results indicate that VDAC exists in a dynamic equilibrium between dimers and
      tetramers and suggest that oligomeric VDAC may be involved in mitochondria
      mediated apoptosis.

PMID- 15456404
TI  - 2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand, induces rapid
      actin polymerization in HL-60 cells differentiated into macrophage-like cells.
AB  - Delta9-Tetrahydrocannabinol, a major psychoactive constituent of marijuana,
      interacts with specific receptors, i.e. the cannabinoid receptors, thereby
      eliciting a variety of pharmacological responses. To date, two types of
      cannabinoid receptors have been identified: the CB1 receptor, which is abundantly
      expressed in the nervous system, and the CB2 receptor, which is predominantly
      expressed in the immune system. Previously, we investigated in detail the
      structure-activity relationship of various cannabinoid receptor ligands and found
      that 2-AG (2-arachidonoylglycerol) is the most efficacious agonist. We have
      proposed that 2-AG is the true natural ligand for both the CB1 and CB2 receptors.
      Despite the potential physiological importance of 2-AG, not much information is
      available concerning its biological activities towards mammalian tissues and
      cells. In the present study, we examined the effect of 2-AG on morphology as well
      as the actin filament system in differentiated HL-60 cells, which express the CB2
      receptor. We found that 2-AG induces rapid morphological changes such as the
      extension of pseudopods. We also found that it provokes a rapid actin
      polymerization in these cells. Actin polymerization induced by 2-AG was abolished
      when cells were treated with SR144528, a CB2 receptor antagonist, and pertussis
      toxin, suggesting that the response was mediated by the CB2 receptor and G(i/o).
      A phosphoinositide 3-kinase, Rho family small G-proteins and a tyrosine kinase
      were also suggested to be involved. Reorganization of the actin filament system
      is known to be indispensable for a variety of cellular events; it is possible
      that 2-AG plays physiologically essential roles in various inflammatory cells and
      immune-competent cells by inducing a rapid actin rearrangement.

PMID- 15456405
TI  - Identification and characterization of pleckstrin-homology-domain-dependent and
      isoenzyme-specific Akt inhibitors.
AB  - We developed a high-throughput HTRF (homogeneous time-resolved fluorescence)
      assay for Akt kinase activity and screened approx. 270000 compounds for their
      ability to inhibit the three isoforms of Akt. Two Akt inhibitors were identified
      that exhibited isoenzyme specificity. The first compound (Akt-I-1) inhibited only
      Akt1 (IC50 4.6 microM) while the second compound (Akt-I-1,2) inhibited both Akt1
      and Akt2 with IC50 values of 2.7 and 21 microM respectively. Neither compound
      inhibited Akt3 nor mutants lacking the PH (pleckstrin homology) domain at
      concentrations up to 250 microM. These compounds were reversible inhibitors, and
      exhibited a linear mixed-type inhibition against ATP and peptide substrate. In
      addition to inhibiting kinase activity of individual Akt isoforms, both
      inhibitors blocked the phosphorylation and activation of the corresponding Akt
      isoforms by PDK1 (phosphoinositide-dependent kinase 1). A model is proposed in
      which these inhibitors bind to a site formed only in the presence of the PH
      domain. Binding of the inhibitor is postulated to promote the formation of an
      inactive conformation. In support of this model, antibodies to the Akt PH domain
      or hinge region blocked the inhibition of Akt by Akt-I-1 and Akt-I-1,2. These
      inhibitors were found to be cell-active and to block phosphorylation of Akt at
      Thr308 and Ser473, reduce the levels of active Akt in cells, block the
      phosphorylation of known Akt substrates and promote TRAIL (tumour-necrosis-factor
      related apoptosis-inducing ligand)-induced apoptosis in LNCap prostate cancer
      cells.

PMID- 15456406
TI  - The endo-beta-agarases AgaA and AgaB from the marine bacterium Zobellia
      galactanivorans: two paralogue enzymes with different molecular organizations and
      catalytic behaviours.
AB  - Two beta-agarase genes, agaA and agaB, were functionally cloned from the marine
      bacterium Zobellia galactanivorans. The agaA and agaB genes encode proteins of
      539 and 353 amino acids respectively, with theoretical masses of 60 and 40 kDa.
      These two beta-agarases feature homologous catalytic domains belonging to family
      GH-16. However, AgaA displays a modular architecture, consisting of the catalytic
      domain (AgaAc) and two C-terminal domains of unknown function which are processed
      during secretion of the enzyme. In contrast, AgaB is composed of the catalytic
      module and a signal peptide similar to the N-terminal signature of prokaryotic
      lipoproteins, suggesting that this protein is anchored in the cytoplasmic
      membrane. Gel filtration and electrospray MS experiments demonstrate that AgaB is
      a dimer in solution, while AgaAc is a monomeric protein. AgaAc and AgaB were
      overexpressed in Escherichia coli and purified to homogeneity. Both enzymes
      cleave the beta-(1-->4) linkages of agarose in a random manner and with retention
      of the anomeric configuration. Although they behave similarly towards liquid
      agarose, AgaAc is more efficient than AgaB in the degradation of agarose gels.
      Given these organizational and catalytic differences, we propose that,
      reminiscent of the agarolytic system of Pseudoalteromonas atlantica, AgaA is
      specialized in the initial attack on solid-phase agarose, while AgaB is involved
      with the degradation of agarose fragments.

PMID- 15456408
TI  - PARP inhibition sensitizes p53-deficient breast cancer cells to doxorubicin
      induced apoptosis.
AB  - p53 deficiency confers resistance to doxo (doxorubicin), a clinically active and
      widely used antitumour anthracycline antibiotic. The purpose of the present study
      was to investigate the reversal mechanism of doxo resistance by the potent PARP
      [poly(ADP-ribose) polymerase] inhibitor ANI (4-amino-1,8-naphthalimide) in the
      p53-deficient breast cancer cell lines EVSA-T and MDA-MB-231. The effects of ANI,
      in comparison with doxo alone, on doxo-induced apoptosis, were investigated in
      matched pairs of EVSA-T or MDA-MB-231 with or without ANI co-treatment. Doxo
      elicited PARP activation as determined by Western blotting and immunofluorescence
      of poly(ADP-ribose), and ANI enhanced the cytotoxic activity of doxo 2.3 times
      and in a caspase-dependent manner. The long-term cytotoxic effect was studied by
      a colony-forming assay. Using this assay, ANI also significantly potentiates the
      long-term cytotoxic effect with respect to treatment with doxo alone. Decrease in
      mitochondrial potential together with an increase in cytochrome c release,
      association of Bax with the mitochondria and caspase 3 activation were also
      observed in the presence of ANI. Therefore PARP inhibition may represent a novel
      way of selectively targeting p53-deficient breast cancer cells. The underlying
      mechanism is probably a potentiation of unrepaired DNA damage, shifting from DNA
      repair to apoptosis due to the effective inhibition of PARP activity.

PMID- 15456407
TI  - Differential induction of quinone reductase by phytoestrogens and protection
      against oestrogen-induced DNA damage.
AB  - Quinone reductase (QR) is a phase II detoxification enzyme that plays an
      important role in detoxifying quinones and may help maintain the antioxidant
      function of the cell. We have previously observed that QR is up-regulated by anti
      oestrogens, but not oestrogen, in breast cancer cells via ERbeta (oestrogen
      receptor beta) transactivation. Such QR induction appears to protect breast cells
      against oestrogen-induced oxidative DNA damage, most likely by reducing reactive
      oestrogen metabolites termed catecholestrogen-quinones back to the hydroxy
      catecholestrogens which may be conjugated. We now report that the phytoestrogens
      biochanin A, genistein and resveratrol also up-regulate QR expression in breast
      cancer cells. We observe that regulation can occur at the transcriptional level,
      preferentially through ERbeta transactivation at the electrophile response
      element of the QR gene promoter. By chromatin immunoprecipitation analysis, we
      show binding of ERalpha and ERbeta to the QR promoter, with increased ERbeta
      binding in the presence of resveratrol. Functional studies show that biochanin A
      and resveratrol, but not genistein, can significantly protect against oestrogen
      induced oxidative DNA damage in breast cancer cells. Antisense technology was
      used to determine whether such protection was dependent on ERbeta or QR. Our
      results with resveratrol are consistent with our hypothesis that the protective
      ability of resveratrol is partially dependent on the presence of ERbeta and QR.
      In conclusion, we postulate that phytoestrogen-mediated induction of QR may
      represent an additional mechanism for breast cancer protection, although the
      effects may be specific for a given phytoestrogen.

PMID- 15456409
TI  - Abstracts from the Annual Meeting of the American Epilepsy Society. New Orleans,
      Louisiana, USA. December 3-7, 2004.

PMID- 15456411
TI  - BSCC terminology for cervical cytology: two or three tiers? Why not five, seven
      or even 14?

PMID- 15456412
TI  - Molecular diagnostic cytopathology: definitions, scope and clinical utility.
AB  - Molecular diagnosis is the application of molecular biology techniques and
      knowledge of the molecular mechanisms of disease to diagnosis, prognostication
      and treatment of diseases. Although it is not widely used in routine molecular
      cytological practice, some examples are presented here of the application of
      molecular techniques to the routine cytopathological diagnosis of solid tumours
      and lymphoreticular malignancies. The term 'molecular diagnostic cytopathology'
      is proposed to define the application of molecular diagnosis to cytopathology,
      and the challenges of the introduction of molecular diagnosis into routine
      diagnostic histopathology and cytopathology are discussed. Finally, the
      importance of a combined morphological, immunophenotypic and molecular approach
      to maintain the diagnostic pathologist at the heart of the clinical decision
      making process is emphasized.

PMID- 15456413
TI  - Level of agreement and biopsy correlation using two- and three-tier systems to
      grade cervical dyskaryosis.
AB  - At present, a three-tier system is used to grade cervical dyskaryosis in the UK,
      although the two-tier Bethesda system is used in the United States, and the
      British Society for Clinical Cytology has recommended that a two-tier system be
      implemented here. In this study, we have retrospectively re-graded 117
      conventional cervical smears using both systems to determine the intra- and
      interobserver variation and compare the cytology grading in both systems with the
      final histology. The intra and interobserver agreement was moderate using both
      grading systems, but the agreement between cytology grade and final histology was
      poor in both the two- and three-tier systems, and slightly worse using two-tier
      grading. However, when each of the three histological categories is considered
      separately the two-tier system appears to work better. Therefore, changing the
      way in which cervical dyskaryosis is graded in the UK may result in poorer
      agreement between the cervical smear result and the final histological diagnosis
      if introduced without proper training, monitoring and assessment.

PMID- 15456414
TI  - Five-year follow-up of women with borderline and mildly dyskaryotic cervical
      smears.
AB  - This study investigated the 5-year follow-up status of women with cervical smears
      showing borderline nuclear changes (BNC) or mild dyskaryosis and the effect of
      koilocytosis on the outcome. Thirteen per cent of women with cervical smears
      showing BNC had high-grade cervical intraepithelial neoplasia (CIN). In contrast,
      28% of women with cervical smears showing mild dyskaryosis had high-grade CIN.
      The presence of koilocytosis (24% for borderline smears and 34% for mild
      dyskaryotic smears) did not appear to influence the risk of developing high-grade
      CIN. Our results suggest that the simultaneous implementation of the British
      Society for Clinical Cytology proposed terminology and the colposcopy guidelines
      from the British Society for Colposcopy and Cervical Pathology could have an
      impact on colposcopy services.

PMID- 15456415
TI  - The inadequate smear: does it matter?
AB  - The objective of this study was to quantify the incidence of underlying cervical
      intraepithelial neoplasia (CIN) among women referred for colposcopy with three
      consecutive inadequate smears. The design was a retrospective cohort study
      analysing data from a regional colposcopy database at Cervical Screening Wales.
      Women who were referred to all the colposcopy clinics in Wales with three
      consecutive inadequate smears, the third inadequate smear being taken between 1
      April 2001 and 31 March 2002 constituted the study population. The results of the
      fourth smear taken at the colposcopy clinic after three consecutive inadequate
      smears, the worst biopsy results from any of the subsequent colposcopies and the
      relationship between the result of the fourth smear taken at colposcopy clinic
      and any histology result were the main outcome measures. The accuracy of the
      colposcopic opinion was also examined. Of the 433 women identified as having been
      referred because of three consecutive inadequate smears, 302 were linked to
      either a subsequent smear and/or a biopsy result. An adequate smear result was
      available for 85% of these women when the smear was taken in the colposcopy
      clinic; 77% were reported as negative and 8% were abnormal. Of the 347 women seen
      in the colposcopy clinic, high-grade CIN was seen in 3% and low-grade lesion in
      8%. The sensitivity and specificity of the fourth inadequate smear test in
      predicting underlying CIN were 15% and 84% respectively, with a positive
      predictive value of 8%. The sensitivity and specificity of colposcopy in
      predicting histological CIN among patients with three inadequate smears was 70%
      and 49%, respectively, and the positive predictive value was 44%. This study
      raises the question as to whether three consecutive inadequate smears should be
      considered as an indication for colposcopy, or merely for a further smear to be
      taken in circumstances where there is a greater likelihood getting an adequate
      result.

PMID- 15456416
TI  - Factors predicting successful DNA recovery from archival cervical smear samples.
AB  - Polymerase chain reaction (PCR)-based DNA testing of archival cervical smear
      slides is a useful method of retrospectively establishing the presence of the
      human papillomavirus (HPV) in cervical cells. A cellular DNA recovery test is
      performed in parallel to HPV DNA testing to ensure that sufficient cells are
      present and purification of sample DNA has been successfully performed. Previous
      studies have not comprehensively assessed DNA recovery rates in slides older than
      13 years. We undertook a study to determine the factors impacting DNA recovery in
      436 UK slides dating from 11 to 33 years prior to testing. Overall, a low
      cellular DNA recovery success rate of 29% was obtained but a strong trend was
      observed with increasing recovery rates the older the slides (P < 0.001).
      Recovery rates increased from 22% in the most recent slides collected from 1988
      to 1992, to 61% in the oldest slides, collected in 1970-72. It is likely that
      fixation compounds incorporating acetic acid, introduced in the UK through the
      1980s, have compromised subsequent attempts at PCR amplification. These findings
      emphasize the importance of the original fixation method in the success of DNA
      recovery from archival smear samples.

PMID- 15456417
TI  - Cytopathology in Norway.

PMID- 15456418
TI  - Fine needle aspiration from a left supraclavicular mass.

PMID- 15456419
TI  - Collecting colorectal cancer staging information in Western Australia.

PMID- 15456420
TI  - Another paper on Mirizzi Syndrome?

PMID- 15456421
TI  - Gastric cancer.

PMID- 15456422
TI  - How many surgeons do we need?

PMID- 15456423
TI  - Role of Gastrografin in assigning patients to a non-operative course in adhesive
      small bowel obstruction.
AB  - BACKGROUND: Adhesive small bowel obstruction (SBO) is a common surgical
      emergency. Water soluble contrast agents have been used to identify patients who
      might be treated non-operatively rather than operatively. The present study was
      designed to audit the introduction of such use of Gastrografin contrast into
      clinical practice. METHOD: Patients presenting acutely to hospital with
      clinically suspected and radiologically proven SBO were entered in the study. As
      soon as practicable, 100 mL of undiluted Gastrografin was given either orally or
      by the nasogastric tube (which was then spigotted). After 4 h, a plain supine
      abdominal X-ray (AXR) was taken. If the contrast was seen in the large bowel, and
      there had been no deterioration in the patient's condition, then non-operative
      treatment was continued. If the contrast remained in the small bowel, a clinical
      judgement was made as to whether to proceed with operative intervention. A group
      of historical controls were obtained by a retrospective review of the hospital
      medical records through data obtained from the Department of General Surgery
      Audit System. RESULTS: Twenty-five patients were entered into the study. In 20 of
      these patients the contrast was seen to arrive in the large bowel at 4 h. All of
      these patients completed a non-operative course to full recovery. In another two
      patients a successful decision was made to pursue a non-operative management
      strategy. These 22 patients had a mean hospital stay of 3.9 days. Eighty
      historical controls had successfully completed a non-operative course for SBO.
      They had a mean hospital stay of 5.6 days. This was significantly longer than
      that of the Gastrografin group (P < 0.016, t-test). CONCLUSION: This paper has
      demonstrated that undiluted Gastrografin may be safely used to assign patients to
      a non-operative management plan and this results in a decreased hospital stay.

PMID- 15456425
TI  - Mirizzi syndrome: noteworthy aspects of a retrospective study in one centre.
AB  - BACKGROUND: Mirizzi syndrome is uncommon. It is, however, clinically important,
      as it is associated with an increased incidence of bile duct injury and demands
      more complex surgical techniques. METHODS: A retrospective review of 24
      consecutive cases of Mirizzi syndrome that arose between January 1997 and July
      2002 was performed. A total of 1881 cholecystectomies were performed during that
      period. RESULTS: Of the 24 patients, 19 (79.2%) had Mirizzi type I, four (16.7%)
      had type II, while one (4.2%) had type III disease. Only 54.2% of patients were
      symptomatic prior to presentation. One-third of patients had normal liver
      function tests. Ultrasonography and computed tomography were not helpful in
      diagnosing this entity. Endoscopic retrograde cholangiopancreatography (ERCP) was
      useful to identify cholecystocholedochal fistulas and to allow therapeutic
      endoscopic stenting but failed to pick up the syndrome in half of the patients.
      Inadvertent bile duct injury occurred in four patients (16.7%), all occurred in
      patients without a preoperative diagnosis. Three of the four injuries occurred
      during operations by a senior registrar rather than a consultant. Mirizzi type I
      was managed with either total or subtotal cholecystectomy, while types II and III
      cases were managed with either T-tube insertion or biliary bypass procedures.
      Bile duct injury was managed with T-tube successfully in one patient while the
      rest went on to biliary bypass operations. All except one patient had good
      functional outcomes on follow up. CONCLUSION: The preoperative diagnosis of
      Mirizzi syndrome is a challenge. Only constant vigilance during intraoperative
      dissection of the Calot's triangle will reduce the incidence of bile duct injury
      in Mirizzi syndrome that can occur in both open and laparoscopic surgery.

PMID- 15456427
TI  - Outcomes in sinonasal mucosal melanoma.
AB  - BACKGROUND: The present paper assesses treatment outcomes in a series of 20
      patients with sinonasal mucosal melanoma (SNMM) over 11 years. METHODS: All
      patients who presented to a single institution between 1991 and 2002 with a
      diagnosis of SNMM had their treatment reviewed and outcomes determined. RESULTS:
      Twenty patients presented to our institution with SNMM over the study period. No
      cervical node or metastatic involvement was detected at presentation. The most
      common site of involvement was the nasal cavity (17/20). The majority of patients
      received initial surgery followed by radiotherapy (15/20). At the completion of
      treatment 14 patients had no disease evident. The median time to failure in these
      patients was 12 months. Of these patients 10 relapsed, including six who had
      metastatic failure only. Fifteen patients died due to disease. Median overall
      survival was 17 months, with a 2-year overall survival of 23%. In univariate
      analysis, patients with advanced tumours (T3-4) had a 4.3 times greater risk of
      dying than patients with early tumours (T1-2). CONCLUSIONS: Patients with SNMM
      have poor outcomes with conventional therapy. Full staging prior to treatment is
      recommended. Aggressive treatment carrying significant morbidity is justified
      only for patients with early stage disease.

PMID- 15456428
TI  - Current management of gall bladder perforations.
AB  - BACKGROUND: Gall bladder perforation is a serious complication of acute
      cholecystitis. The purpose of the present study is to evaluate the presenting
      symptoms, diagnosis and management of patients with gall bladder perforations.
      METHODS: A retrospective study was undertaken of 31 consecutive patients with
      gall bladder perforation in a single unit of a tertiary referral hospital,
      between January 1996 and December 2001. RESULTS: The incidence of gall bladder
      perforation was 5.9% of all cases of acute cholecystitis. Associated comorbidity
      was quite common (58%). Ultrasound and computed tomography scans of the abdomen
      are sensitive investigations. Ultrasound guided percutaneous drainage helps in
      tiding over the emergency. The morbidity (35%) and mortality (9.6%) is
      considerable. CONCLUSION: The patterns of presentations, diagnosis and management
      of gall bladder perforation are changing. But there is scope for improvement.

PMID- 15456430
TI  - Is bilateral duplex scanning necessary in patients with symptoms of deep venous
      thrombosis?
AB  - BACKGROUND: Venous duplex ultrasound scanning (VDUS) has been shown to be an
      accurate non-invasive means to diagnose symptomatic deep venous thrombosis (DVT).
      The aim of our study was to determine whether bilateral VDUS is necessary in
      patients who present with symptoms of DVT. METHODS: We retrospectively reviewed
      the results of bilateral lower extremity VDUS performed on 1029 inpatients at
      Royal Prince Alfred Hospital in the 24 months from 1 January 1998 to 31 December
      1999. RESULTS: Of the 1029 patients, 705 (69%) presented with unilateral symptoms
      and 324 (31%) with bilateral symptoms. The overall incidence of DVT was 168 (16%
      of 1029 patients). In 705 patients with unilateral symptoms the diagnosis of DVT
      was confirmed in 120 (17.0%), of whom 20 (16.7%) had unsuspected bilateral DVT.
      There were 12 patients (1.7% of the 705 patients) who had DVT in the asymptomatic
      limb, without DVT identified in the symptomatic limb. Overall there were 32 (5%
      of 705) patients with unilateral symptoms who had unsuspected DVT in the
      asymptomatic limb. Of the 20 patients with bilateral DVT, only one patient had
      more extensive DVT in the asymptomatic limb than in the symptomatic limb, that
      was therefore likely to alter treatment. Bilateral symptoms of DVT were present
      in 324 (31.5%) patients, 48 (14.8%) of whom were found to have DVT. Nineteen
      (39.6%) of these DVTs were bilateral. CONCLUSION: Overall the diagnostic yield of
      VDUS was low in this study, with an incidence of 16% of DVT detected in
      symptomatic patients. Techniques that improve the diagnostic yield of VDUS in
      symptomatic patients are required. A significant proportion (23%) of the DVT
      detected in this study were bilateral, and a small but significant proportion
      (10%) of DVT found in patients presenting with unilateral symptoms were only in
      the asymptomatic contralateral limb. Our study supports bilateral VDUS in
      symptomatic inpatients, as the detection of DVT in asymptomatic limbs aids future
      patient management if symptoms develop in the asymptomatic limb.

PMID- 15456431
TI  - Lymph node metastasis of gastric cancer: comparison of Union International Contra
      Cancer and Japanese systems.
AB  - BACKGROUND: The pN classification of gastric cancer (GC) in the Japanese system
      (Japanese Gastric Cancer Association; JGCA) is based on the site and distance of
      metastatic nodes from the primary tumour. Union International Contra Cancer
      (UICC) has recently proposed a classification system based on the number of nodes
      involved (TNM-1997). The aim of the present study is to assess which
      classification system is more suitable for providing a prognosis in advanced GC
      with lymph node metastasis. METHODS: A total of 224 patients who underwent
      curative gastrectomy (R0: UICC-TNM and Resection A and B: JGCA) and D2
      lymphadenectomy between 1990 and 1999, and diagnosed as pT2, pT3 and pT4 GC were
      enrolled. Patients were followed until the end of 2002. The disease-free survival
      rates of patients were compared between the two-stage systems (UICC-TNM and
      JGCA). RESULTS: Using the JGCA system, there was a significant difference between
      the two survival curves (pN0 and pN1, P = 0.025; pN1 and pN2, P < 0.001; pN2 and
      pN3, P = 0.031), but the 5-year survival rate of 27 pN2 patients (32.7%) was not
      significantly different from that of 14 pN3 patients (34.3%, P = 0.994) using the
      UICC-TNM. In 47 patients with JGCA pN2, the 5-year survival rate of 18 patients
      with UICC-TNM pN1 (42.9%) was not significantly different from that of 18
      patients with UICC-TNM pN2 (25.2%, P = 0.422) or from that of 11 patients with
      UICC-TNM pN3 (24.2%; P = 0.383). CONCLUSIONS: The JGCA system is more suitable
      for estimating the prognosis of Japanese patients with advanced GC than the UICC
      TNM.

PMID- 15456432
TI  - OK-432 and lymphatic malformations in children: the Starship Children's Hospital
      experience.
AB  - BACKGROUND: Surgery has previously been the mainstay of treatment for lymphatic
      malformations but has attendant problems of marked scarring, high chance of
      recurrence and potential nerve damage. Alternative management for these lesions
      involves the intralesional injection of OK-432. The present paper reviews OK-432
      use in lymphatic malformations in children. METHODS: A retrospective chart review
      was carried out of children undergoing intralesional OK-432 therapy from the
      Departments of Paediatric Surgery, Paediatric Otolaryngology and Plastic Surgery
      at Starship Children's Hospital, Auckland. RESULTS: Over the past 4 years, seven
      children under the age of 5 years underwent OK-432 therapy as day-case procedures
      requiring between one and seven procedures each. Four children had lesions
      involving the axilla/chest wall, two involved extra-mylohyoid tissues in the neck
      and one child had lymphatic malformation involving tongue, floor of mouth and an
      extra-mylohyoid component. Spontaneous haemorrhage into a cystic space may be the
      cause of the observed partial resolution of the lymphangiomas in two. A predictor
      of a successful outcome was the ability to aspirate fluid prior to injection.
      Ultrasound guidance was useful to localize the lesions for aspiration and
      injection. Macrocystic lesions respond well to OK-432 therapy but the response of
      microcystic or cavernous lesions to OK-432 is disappointing and surgery remains
      the definitive treatment for these microcystic lesions. CONCLUSION: OK-432
      appears to be a safe and effective treatment for the macrocystic component of
      lymphatic malformations.

PMID- 15456433
TI  - Cat bites of the hand.
AB  - BACKGROUND: Cat bites are the second most common mammalian bites. Cat bites of
      the hand in particular represent a potentially devastating problem in terms of
      wound infection and long-term disability if not treated appropriately. The
      purpose of the present study is to give an overview of demographics, management
      and follow up of the patients with cat bite injuries of the hand treated at the
      Royal Hobart Hospital. METHODS: Retrospective and prospective data of all
      patients with cat bites of the hand seen at the Royal Hobart Hospital for a
      period of 3 years (January 2000 to April 2003) were collected. Demographics,
      anatomical site, presentation, assessment, investigations, management and follow
      up of the patients with this type of injury were analysed. The accuracy of the
      obtained data was checked by analysing questionnaires returned by our patients.
      RESULTS: Forty-one patients were treated for cat bites of the hand. Twenty-six
      were managed in the department of emergency medicine and 15 were admitted and
      managed by the department of plastic and reconstructive surgery. Five of 15
      admitted patients required surgery. Compliance was not a major problem in our
      study as very few patients were lost to follow up. Almost all patients had close
      follow up and extensive hand physiotherapy achieving overall good long-term
      results. Out of 39 patients who were sent questionnaires only one indicated long
      term problems with the hand (response rate 46%). CONCLUSION: Appropriate early
      treatment of cat bites of the hand is the key to success. Treatment with
      antibiotics, surgical drainage, debridement and copious irrigation, and use of
      corticosteroids in some cases, proved to be effective. Hand elevation and
      intensive physiotherapy after a short period of immobilization is critical. We
      believe that prophylactic antibiotics should be given even in case of a minor
      infection following cat bites of the hand. Clear guidelines for clinical
      recognition of infection, hospital admission and management are provided in our
      study.

PMID- 15456434
TI  - The demand for surgery: an analysis of referrals from Australian general
      practitioners.
AB  - BACKGROUND: Optimal planning for surgical training and the surgical workforce
      requires knowledge of the need and demand for surgical care in the community.
      This has previously relied on indirect indicators, such as hospital throughput.
      We aimed to describe referrals from general practitioners (GPs) to surgeons in
      Australia using a classification of surgical disorders developed especially for
      primary care settings. METHODS: Terms in the International Classification of
      Primary Care Version 2-Plus were reclassified into categories delineated by
      specialist surgeons, resulting in the Surgical Nosology In Primary-care Settings
      (SNIPS). Referrals to surgeons were analysed using data on 303,000 patient
      encounters by a random sample of 3030 GPs involved in the Bettering the
      Evaluation and Care of Health (BEACH) study. RESULTS: Thirty-two per cent
      (143,013) of all problems were classified as potential surgical problems, of
      which 9.5% (13,570) were referred to surgeons at an overall rate of 44.8
      referrals per 1000 GP encounters. Patients with surgical problems were
      significantly older than the overall general practice patient population. Women
      and patients with health care cards were significantly less likely than men and
      patients without health care cards to be referred when a surgical problem was
      managed by the GP. Forty-two per cent of all surgical referrals were accounted
      for by the following categories: skin lesions, skin infection/injury, upper
      gastrointestinal, breast lumps/cancer, spine, knee arthritis/pain, knee
      injury/instability, infective and non-infective ear disorders. Many commonly
      referred problems are usually managed as outpatients. CONCLUSIONS: The data from
      this study may have application for surgical workforce planning and ensuring
      trainees receive adequate exposure to commonly referred conditions. The
      classification system (SNIPS) may be useful for future research concerning the
      interface between primary care and specialist surgical practice.

PMID- 15456435
TI  - Diverticulectomy is inadequate treatment for short Meckel's diverticulum with
      heterotopic mucosa.
AB  - BACKGROUND: Meckel's diverticulum is a vestigial remnant of the vitellointestinal
      duct that may occasionally contain heterotopic gastric mucosa thought to arise
      from residual yolk sac cells. This may cause significant rectal bleeding, the
      source of which may be difficult to identify. The present paper addresses the
      question of whether the choice of resection technique should depend on the
      macroscopic appearance of the Meckel's diverticulum. METHODS: A retrospective
      analysis of patients with resected Meckel's diverticulum at Prince of Wales and
      Sydney Children's Hospitals between 1992 and May 2003 was performed. The external
      appearance was expressed as a height-to-diameter ratio (HDR) and the presence or
      absence of macroscopic thickening was recorded. The morphology was then
      correlated with the presence and site of the heterotopic gastric mucosa (HGM).
      RESULTS: Seventy-seven patients were identified with an age range between 1 day
      and 92 years. Fifty-seven (74%) of the patients were men. Presenting symptoms
      were gastrointestinal bleeding (11.7%), diverticulitis (15.6%), volvulus (2.6%),
      intussusception (10%) and umbilical fistula (7.8%). Fifty-seven per cent of the
      resected Meckel's diverticulae were found incidentally. Eight patients underwent
      a technetium pertechnate nuclear Meckel's scan. The Meckel's scan detected only
      two of seven patients with HGM on pathological examination. Twenty-nine (38%)
      patients underwent diverticulectomy and 48 (62%) small bowel resection. Ectopic
      mucosa was found in 25 (32.5%) patients. Of the Meckel's diverticula that were
      defined as long (HDR >or=2.0) and containing HGM, five of five (100%) had the
      ectopic mucosa in the diverticular tip and body only. Of those that were short
      (HDR <2.0) there was a wide distribution of HGM sites with 12 (60%) involving the
      whole diverticulum including the base and eight (40%) involving the tip and body
      only. The presence or absence of macroscopic thickening was described in 18
      resected Meckel's diverticula. Thirteen (72%) were described as thickened in the
      operation report and six of these 13 (46%) were found to have HGM. One of the
      seven (14%) Meckel's diverticulae with HGM was thought to be of normal appearance
      and was therefore undetected. CONCLUSION: Simple transverse resection is not
      recommended for the short Meckel's diverticulum. A HDR of 2.0 is recommended as
      the cut-off when deciding on the most appropriate operation. The external
      appearance of the Meckel's diverticulum does not predict the presence of HGM and
      is therefore an unreliable indicator to aid resection decisions when presented
      with an incidental Meckel's diverticulum.

PMID- 15456436
TI  - Randomized trial of a pain control infusion pump following inguinal hernia
      repair.
AB  - BACKGROUND: Continuous ambulatory analgesia following various surgical procedures
      is gaining popularity. The purpose of the present paper is to evaluate this form
      of analgesia following open anterior inguinal hernia repair by way of a pain
      control infusion pump (PCIP). METHODS: Forty-eight consecutive patients scheduled
      for inguinal hernia repair were enrolled in a double-blind, randomized, placebo
      controlled trial. Following the repair, a catheter was placed in the wound
      connected to an external PCIP, delivering either ropivacaine or normal saline at
      a fixed rate of 4 mL/ h. Regular 4-hourly postoperative pain observations
      according to a Visual Analogue Score (VAS) and any rescue opioid requirements
      were recorded, at different levels of mobility. RESULTS: Data analysis included
      23 (ropivacaine) and 24 (saline) patients in each group, with one exclusion.
      There were no adverse effects of the PCIP in either group. Patients in the
      ropivacaine group ('active pump') had lower mean pain scores and less rescue
      analgesia compared to the saline group ('placebo pump'). This clinical effect was
      found to be more striking at increased levels of mobility. Importantly, no
      patients in the ropivacaine group required any rescue analgesia after the first 4
      h block postoperatively. CONCLUSION: The PCIP provided safe and adequate
      analgesia following inguinal hernia repair. It provided effective analgesia
      especially when patients were mobilizing. This has implications for earlier
      discharge from hospital and associated cost-savings.

PMID- 15456437
TI  - Endoscopic totally extraperitoneal inguinal hernioplasty for recurrence after
      open repair.
AB  - BACKGROUND: Whether endoscopic totally extraperitoneal inguinal hernioplasty
      (TEP) for recurrent inguinal hernia is as safe and efficacious as that for
      primary inguinal hernia has rarely been examined. The objective of the present
      study was to compare the early and late outcomes of TEP for primary and recurrent
      inguinal hernia. The clinical pattern of recurrence after previous open repair of
      inguinal hernia was also examined. METHODS: Between August 1999 and November
      2003, 100 consecutive patients who underwent TEP for recurrent inguinal hernia
      were recruited. The outcomes of these patients were compared to a randomly
      selected control group (n = 100) who had TEP for primary inguinal hernia during
      the same period. All data had been prospectively collected and analysed. RESULTS:
      Demographic features were comparable between the two groups. The recurrent group
      had a significantly higher incidence of direct inguinal hernia than the control
      group (P < 0.001). Comparison of operative duration, postoperative morbidity,
      pain score, length of hospital stay and time taken to resume normal activities
      showed no significant differences between the two groups. However, the incidence
      of peritoneal tear in the recurrent group (46%) was significantly higher than
      that of the control group (28%) (P < 0.05). With a mean follow-up of 1 year, the
      incidences of recurrence and chronic groin pain were similar for both groups.
      CONCLUSION: Early and late outcomes of TEP for recurrent inguinal hernia were
      equivalent to those for primary inguinal hernia but a higher incidence of
      peritoneal tear was encountered during TEP for recurrent inguinal hernia. A
      predominance of direct hernia was observed in the recurrent group.

PMID- 15456438
TI  - The Surgical Acute Care Unit (SACU): effects on surgical workload and mortality.
AB  - BACKGROUND: A surgical acute care unit (SACU) is designed to provide level 1 care
      for surgical patients. The aim of the present study was to audit the effects of
      the introduction of a SACU in a teaching hospital surgical department. METHODS: A
      retrospective case-note audit of all admissions to the newly established SACU
      over the first 6 months was performed. Expected mortality and morbidity was
      calculated using POSSUM (physiological and operative severity score for the
      enumeration of mortality and morbidity) scores. Critical care data for the same
      period and the 6 months prior to the SACU opening was examined to determine any
      effect on critical care workload. RESULTS: The SACU admitted 131 patients during
      the audit period. There was no significant difference between predicted and
      observed mortality or morbidity. There was no effect on critical care length of
      stay after the SACU opened. Many patients who would have needed critical care
      beds before the SACU opened were admitted directly to the SACU after it opened.
      CONCLUSIONS: This audit demonstrates that the provision of a surgical acute care
      unit allows many patients who would normally need to be admitted to the critical
      care unit for postoperative care to be safely admitted to level 1 care beds.

PMID- 15456439
TI  - Comparison of pulmonary hydatid cysts in children and adults.
AB  - BACKGROUND: The purpose of the present study was to compare the clinical features
      and the surgical approaches of the pulmonary hydatid cysts in children and
      adults. METHODS: One hundred and thirty-four patients, operated on for pulmonary
      hydatid cysts over the last 10 years were retrospectively evaluated in two
      groups: 39 children who were younger than 18 years old (29%) and 95 adults (71%).
      The patients in each group were analysed according to their clinical,
      radiological and surgical findings. RESULTS: The frequency of pulmonary hydatid
      cysts in children was significantly higher in boys (74%) than in girls (26%).
      However, there was no sex tendency in adults (52% in male vs 48% in women). The
      sex difference in hydatid cyst frequencies between adults and children was
      significant (P < 0.05). Among preoperative pleural complications, pneumothorax
      (15.5%) in children and empyema (11%) in adults were more frequent. The frequency
      of concomitant hepatic cysts was less in children than in adults (33%vs 79%).
      Huge pulmonary cysts (=10 cm) were more common in children (31%) than in adults
      (22%). Cystotomy with capitonnage was the most frequently preferred method in
      both groups. Postoperative complications developed in six children (16%) and 19
      adults (19%), and were more frequent in patients with huge cysts (27%vs 16%). No
      recurrence was observed in both groups. CONCLUSIONS: Isolated pulmonary cysts are
      more common in children than adults. The cysts also tend to be bigger in children
      than adults. The frequency of concomitant hepatic cysts is less in children.
      Because of higher lung expansion ability and improvement capacity in children,
      resection should be avoided and lung saving surgical procedures should be
      performed. In spite of differences observed in the clinical features it does not
      change the treatment of pulmonary hydatid cysts in children.

PMID- 15456440
TI  - Paediatric constipation for adult surgeons - article 2: new microscopic
      abnormalities and therapies.
AB  - Chronic constipation is a common condition in both adults and children. Children
      with chronic constipation frequently have symptoms that continue into adulthood.
      In the second part of the review we describe advances in the identification of
      abnormalities in the control of motility. The role of neurotransmitters in both
      paediatric and adult constipation is examined and the radical rethink of colonic
      dysmotility caused by the re-emergence of interstitial cells of Cajal is
      discussed. The recognition of chronic constipation as an heterogenous condition
      has led to the introduction of new therapies. Antegrade washouts through appendix
      stomas and an exciting new treatment with electrical interferential therapy may,
      in the future, result in a less invasive approach to the management of chronic
      constipation. An improved understanding of the assessment and management of
      chronic constipation in childhood is also likely to reduce the frequency and
      morbidity of chronic constipation in adults.

PMID- 15456441
TI  - Model for collecting colorectal cancer staging information in Western Australia.
AB  - BACKGROUND: There is recognition that to improve the management of patients with
      cancer we need to monitor outcomes, especially survival outcomes based on tumour
      stage. Unfortunately, there are few centres in Australia that can provide stage
      stratified survival information, despite the large investments that have been
      made in data collection. The aim of this study was to collect staging information
      for all colorectal cancers diagnosed in Western Australia over a 12-month period.
      This information could then serve as a basis for more meaningful analysis.
      METHODS: A project officer was appointed to coordinate a programme through the
      Western Australian Cancer Registry. A consensus was reached among pathologists on
      the standardized reporting of colorectal cancers to the registry. Clinicians were
      asked to provide, on pathology request forms, information on tumour location, the
      presence of metastatic disease (on X-ray or at laparotomy), and type of surgery.
      Use was also made of existing hospital and unit based databases to acquire and
      crosscheck information. RESULTS: Over a 12-month study period, 1008 patients with
      colorectal cancers were notified to the Cancer Registry. Their mean age was 69.1
      years (range 23-100 years), 56% were men and 44% women. The rectum was the most
      common site for disease location (32.5%). At cessation of the project, 743
      patients (74%) were fully staged, with a further 221 patients (22%) having
      completed data on tumour depth of penetration and nodal status, but insufficient
      information on the presence of metastases. The stage distributions were: stage I 
      20.5%; stage II - 29.9%; stage III - 26.2%; stage IV - 23.4%. CONCLUSIONS: It is
      feasible to collect staging information on colorectal cancers notified to a
      population based cancer registry. This information will be invaluable for stage
      stratified survival analysis and research.

PMID- 15456442
TI  - C-reactive protein may be a marker of bacterial translocation in experimental
      intestinal obstruction.
AB  - BACKGROUND: C-reactive protein (CRP) is used as a marker of intestinal ischaemia.
      This study evaluated whether CRP levels can be used to detect ischaemia-induced
      (strangulated) intestinal obstruction and subsequent bacterial translocation.
      METHODS: Forty-eight rats, divided into four groups underwent the following
      procedures: anaesthesia alone (native controls), laparotomy (sham-operated
      controls), or surgical induction of simple or strangulated intestinal obstruction
      (simple and strangulated obstruction groups, respectively). Blood samples were
      collected for culture and serum CRP analysis. In addition, liver and mesenteric
      lymph node (MLN) specimens were collected for culture, to determine the presence
      of bacterial translocation; and ileal segments, for histopathological
      investigation. RESULTS: CRP levels and rates of bacterial translocation,
      expressed as colony forming units (cfu) per gram wet tissue, were higher in both
      intestinal obstruction groups than in the native and sham-operated control groups
      (P < 0.001 for both). The increases in CRP levels paralleled increases in the
      number of cfu in the MLN and liver cultures (P < 0.01). Compared to controls,
      animals in the obstruction groups also had a higher incidence of positive blood
      cultures (P < 0.005) and greater histopathologic evidence of inflammatory
      infiltration of the lamina propria (P < 0.01). However, no significant difference
      between the simple and strangulated obstruction groups was observed. CONCLUSION:
      CRP levels increase with the severity of bacterial translocation in acute
      intestinal obstruction but do not permit discrimination between simple and
      strangulated intestinal obstruction.

PMID- 15456443
TI  - Imaging of an enterovaginal fistula with flexible colposcopy, an endoscopic
      retrograde cholangiopancreatography cannula and radiographic screening.
AB  - The diagnosis of a rectovaginal or enterovaginal fistula is mostly made by a
      careful historical of a faecal vaginal discharge. When a rectovaginal fistula is
      low, an examination will demonstrate it with ease. However, when there is a high
      and small fistula into the vault or the fornix of the vagina, traditional methods
      of small bowel enema and barium enema may not demonstrate the fistula. Ultrasound
      and magnetic resonance imaging may demonstrate a fistula but not the nature of
      the bowel involved. Vaginography has been the most successful imaging method to
      date. Demonstrating an enterovaginal fistula and substantiating whether or not
      the rectum, the small bowel alone or both are implicated are important for
      operation planning; a fistulogram through the vagina by endoscopic method is a
      simple and useful adjunct to the available methods of imaging enterovaginal
      fistulas. We report a case and discuss a technique of endoscopic fistulography
      through a small fistulous opening high in the vagina. We believe that this
      technique is accurate, simple and complementary to vaginography in demonstrating
      an enterovaginal fistula.

PMID- 15456444
TI  - Towards a hybrid philosophy of surgical education.
AB  - BACKGROUND: Surgical training involves a complex amalgam of skills. This
      publication seeks to incorporate concepts about higher education into a
      philosophy of surgical education. METHODS: The core of the present review is
      derived from a literature search of a computer database (Medline). The notion of
      competence is used to illustrate the concept of a philosophy of surgical
      education. CONCLUSION: A predefined philosophy of surgical education may serve as
      a useful reference point when choices arise during the development of surgical
      training.

PMID- 15456445
TI  - Re: Adrenocortical oncocytoma: benign or malignant?

PMID- 15456446
TI  - Re: Modified Limberg Flap reconstruction compares favourably with primary repair
      for pilonidal sinus surgery.

PMID- 15456447
TI  - Expectoration of endobronchial sarcoma metastasis.

PMID- 15456448
TI  - Aorto-appendiceal fistula presenting with bleeding per rectum.

PMID- 15456449
TI  - Solid-pseudopapillary neoplasm of pancreas.

PMID- 15456450
TI  - Guillain-Barre syndrome following oesophagectomy.

PMID- 15456451
TI  - Magnetic resonance spectroscopy of primary carcinoid tumour of the prostate.

PMID- 15456452
TI  - Mucinous cystadenoma of the appendix.
AB  - Mucinous neoplasms of the Appendix are rare conditions, usually diagnosed
      intraoperatively or postoperatively on the pathology report. They have an
      association with colonic and ovarian neoplasms, and spillage can result in
      pseudomyxoma peritonei. While appendicectomy is adequate treatment for
      cystadenomas, cystadenocarcinomas require a right hemicolectomy. Open approach is
      recommended for the surgical treatment of these lesions.

PMID- 15456453
TI  - Management of extensive congenital fibrosarcoma with preoperative chemotherapy.

PMID- 15456454
TI  - Splenectomy in severe haemophilia.
AB  - The management of any surgical condition in a haemophilia patient is a
      challenging problem for the surgeon. It is particularly difficult if the patient
      presents in extremis, with no apparent cause for their collapse. We report a case
      of successful management of spontaneous splenic rupture in a severe haemophiliac,
      and review the literature associated with this unusual condition.

PMID- 15456455
TI  - Management of urethral metastasis from colorectal carcinomas.

PMID- 15456457
TI  - Review article: trials on reflux disease -- the role of acid secretion and
      inhibition.
AB  - The importance of gastric acid in the pathophysiology of gastro-oesophageal
      reflux disease is substantiated by the extraordinary therapeutic success of acid
      inhibition in the management of the disease. The influence of many risk factors
      for gastro-oesophageal reflux disease is also mediated through their effect on
      gastric acid secretion and acid reflux. Helicobacter pylori reduces the risk of
      gastro-oesophageal reflux disease by causing corpus gastritis and reducing
      gastric acid output. The geographical and temporal trends of H. pylori infection
      in human populations and its influence on gastric acid secretion are responsible
      for much of the apparent epidemiology of gastro-oesophageal reflux disease. On
      average, intra-oesophageal exposure to acid is higher in patients who respond
      poorly to antisecretory medication. It also tends to increase with increasing
      severity of reflux disease. However, gastric acid secretion and intra-oesophageal
      acid exposure vary markedly in reflux patients. The degrees of gastric or intra
      oesophageal acidity do not allow the prediction of the presence or severity of
      gastro-oesophageal reflux disease in the individual subject. The many clinical
      trials on gastro-oesophageal reflux disease indicate that the reflux of gastric
      acid constitutes an essential mechanism in the development of this disease, but
      that additional and partly unknown risk factors must contribute to its aetiology
      and promote its occurrence in the individual patient.

PMID- 15456458
TI  - Practical examples: trials and conclusions -- an interactive segment.
AB  - There is a requirement for a critical review of the literature published in the
      field of reflux disease management, particularly when the literature is used as a
      basis for the adoption of specific interventions into everyday practice. Numerous
      published studies are valid and robust, but many are not. Particularly common is
      the over-interpretation of positive studies based on small patient numbers, which
      may be subject to publication bias. Claims of equivalence are invalid without a
      pre-specified level of equivalence and adequate power to measure this. More
      generally, a lack of pre-defined primary end-points, clinically relevant and
      measured appropriately, is a common feature of reflux trial methodology.

PMID- 15456459
TI  - Review article: towards the optimization of symptom evaluation in reflux disease.
AB  - A recent workshop has taken stock of the processes used for the evaluation of
      reflux disease symptoms. Such evaluations are vital both for routine clinical
      practice and for the critical assessment and comparison of therapeutic options.
      The workshop endorsed the importance of the assessment of symptom patterns for
      the diagnosis of reflux disease. Patient self-report symptom questionnaires were
      considered to be potentially valuable instruments, but have been researched
      relatively little in reflux disease. On the basis of a survey of the literature
      and data from generic methodological research, the workshop concluded that
      virtually all trials of the therapy of reflux disease have used too few response
      options for a sensitive definition of symptom status, and recommended that six to
      seven response options be used. Modified Likert scales with defined individual
      response options and structured patient self-report, rather than physician
      assessment, were considered to be the best approaches. These views on symptom
      status assessment are not reflected fully in the current practice of reflux
      disease clinical trials. Furthermore, the terminology used to describe symptom
      status is frequently ambiguous or tautological. Quality of life measures were
      acknowledged as valid and useful secondary measures of therapeutic benefit. By
      contrast, evaluation of the state of the art of assessment of patient
      satisfaction with therapy led to the conclusion that the methodology for this
      particular assessment was still in its infancy. The outputs of the workshop
      revealed many aspects of the assessment of reflux disease that would benefit from
      further research and development. A report on the detailed outputs of the
      workshop has been published recently.

PMID- 15456460
TI  - Review article: gastric pH -- the most relevant predictor of benefit in reflux
      disease?
AB  - Summary In patients with gastro-oesophageal reflux disease, the pH of refluxed
      gastric contents has a direct bearing on disease severity and oesophageal damage.
      A pH of 4 has been defined as a threshold below which refluxed gastric contents
      become injurious to the oesophagus. Studies in patients with erosive oesophagitis
      have shown that the 8-week healing rates produced by acid suppressive therapy are
      related to the duration of time over a 24-h period that the intragastric pH > 4.
      The most effective agents, providing more hours with gastric pH > 4 and higher
      healing rates in erosive oesophagitis patients, are the proton pump inhibitors.
      The intragastric pH is often used to gauge the efficacy of acid suppressive
      therapies. There are several factors, however, that may affect the clinical
      relevance of such data, and these should be taken into account when comparing the
      effectiveness of different therapies. Firstly, because of inter-individual
      variation, studies comparing therapies should be of a crossover design, so that
      responses to therapy are measured in the same individuals. Secondly, the
      Helicobacter pylori status of the individual should be known, as H. pylori
      infection has been shown to increase intragastric pH readings when examining the
      effect of acid suppressive therapy. Other factors, such as positioning of the pH
      electrode and the duration of previous therapy, also need to be standardized when
      using intragastric pH to assess the efficacy of different therapies. Crossover
      studies comparing standard doses of different proton pump inhibitors have shown
      that esomeprazole 40 mg produces a significantly greater amount of time at
      intragastric pH > 4 on day 5 of treatment than standard doses of other proton
      pump inhibitors. The correlation between greater efficacy in acid suppression and
      clinical benefit is supported by the findings that esomeprazole 40 mg is the only
      proton pump inhibitor to provide greater 8-week healing rates in patients with
      erosive oesophagitis than both omeprazole and lansoprazole. These data all
      suggest strongly that intragastric pH monitoring is an effective surrogate marker
      and a relevant predictor of outcome in gastro-oesophageal reflux disease.

PMID- 15456461
TI  - Review article: gastro-oesophageal reflux disease -- how wide is its span?
AB  - Symptoms of gastro-oesophageal reflux disease are highly prevalent in Western
      countries; however, it is less certain how many individuals with heartburn have
      clinically relevant disease. Although the prevalence of gastro-oesophageal reflux
      disease in Asia is substantially lower, the incidence may be increasing. How much
      of this increase is explained by the increasing recognition of heartburn in
      clinical practice, dietary changes and increasing obesity, or the eradication of
      Helicobacter pylori, remains unclear. There has been speculation that endoscopy
      negative reflux disease represents a separate entity from reflux oesophagitis (as
      defined by the Los Angeles classification), but the evidence that might support
      this proposal is unconvincing. Patients with chronic reflux symptoms have a
      higher risk of Barrett's oesophagus, and the increased risk of developing
      oesophageal adenocarcinoma in individuals with a long history of heartburn is
      also well documented, but whether this always occurs via Barrett's oesophagus is
      debatable. Moreover, treatment with standard-dose antisecretory therapies and
      anti-reflux surgery seems unlikely, based on current evidence, to reduce the
      cancer risk in patients with Barrett's oesophagus. Gastro-oesophageal reflux
      disease has also been implicated in an increasing array of other conditions, but
      arguably in these settings it is often over-diagnosed.

PMID- 15456463
TI  - Review article: towards consistency in the endoscopic diagnosis of Barrett's
      oesophagus and columnar metaplasia.
AB  - Barrett's oesophagus is associated with severe reflux disease and is a risk
      factor for oesophageal adenocarcinoma. However, there is a lack of consensus on
      how to assess the presence and extent of Barrett's oesophagus in clinical
      practice. A diagnosis of Barrett's oesophagus is currently based on the
      recognition of an abnormal oesophageal mucosa at endoscopy. However, a diagnosis
      cannot be made solely on this basis, and a true diagnosis requires the
      identification of an area suspicious for columnar metaplasia at endoscopy,
      followed by histological confirmation. Currently, difficulties in the assessment
      of Barrett's oesophagus include a lack of consistent definitions of endoscopic
      landmarks (such as the gastro-oesophageal and squamo-columnar junctions), a lack
      of standardization of descriptions of the extent of Barrett's oesophagus, and
      limited communication between the endoscopist and the pathologist, which hampers
      accurate histological confirmation. It is therefore important to develop an
      endoscopic description of Barrett's oesophagus, with a clear definition of
      endoscopic landmarks, to determine, amongst other things, whether anti-reflux
      therapy produces regression or a reduction in the length of Barrett's oesophagus.
      With this background, a subgroup of the International Working Group on the
      Classification of Oesophagitis was charged with developing a simple, practicable
      classification system, suitable for use with standard endoscopes, which would be
      easy to apply in clinical practice and in large clinical studies. Described in
      this review are a series of propositions and an overview of the 'CM
      classification', developed by the International Working Group on the
      Classification of Oesophagitis, to facilitate the endoscopic description of
      Barrett's oesophagus. It is hoped that these propositions will be the first step
      in the development of standard endoscopic diagnostic criteria for Barrett's
      oesophagus, relevant to clinical practice and clinical research.

PMID- 15456464
TI  - Review article: prevalence of Barrett's oesophagus and metaplasia at the gastro
      oesophageal junction.
AB  - Barrett's oesophagus, a complication of chronic gastro-oesophageal reflux
      disease, is the premalignant lesion for oesophageal and gastro-oesophageal
      junction adenocarcinoma. Described in the 1950s by Norman Barrett, the diagnostic
      criterion for this lesion has evolved significantly over the last three decades.
      Endoscopic Barrett's oesophagus requires the recognition of columnar mucosa in
      the distal oesophagus; documentation of metaplastic tissue is confirmed by random
      biopsies. Given this changing definition of Barrett's metaplasia, the prevalence
      rates vary in the literature depending on the diagnostic criteria applied.
      However, it is generally accepted that approximately 10% of patients with chronic
      gastro-oesophageal reflux disease will be diagnosed with this condition. There
      are no population-based studies on the prevalence of Barrett's oesophagus, but
      emerging data indicate that it may be equally prevalent in asymptomatic
      individuals. These studies require confirmation. Although the incidence of
      oesophageal adenocarcinoma is increasing rapidly, it is unclear whether the true
      incidence of Barrett's oesophagus is increasing at the same time. On the other
      hand, metaplasia at the gastro-oesophageal junction appears to be distinct from
      Barrett's oesophagus, is probably not related to chronic gastro-oesophageal
      reflux disease and is a common finding if routine biopsies are obtained at the
      gastro-oesophageal junction. This article reviews our current understanding of
      the diagnosis, definition and prevalence of both of these lesions.

PMID- 15456465
TI  - Review article: oesophago-gastric adenocarcinoma -- an epidemiological
      perspective.
AB  - This article reviews the epidemiology of cancers arising in the distal oesophagus
      and proximal stomach, sometimes collectively termed oesophago-gastric junctional
      adenocarcinomas. The several complexities involved in defining this group of
      cancers are considered and the reported increasing trends in incidence are
      reviewed, together with the descriptive epidemiology. The rates of these cancers
      are increasing, but not as dramatically as sometimes reported. They are also more
      common in white males than in other ethnic groups or in females. Although several
      aetiological risk factors have been reported, the two most consistent are an
      elevated body mass index (obesity) and a history of gastro-oesophageal reflux
      disease. Reflux is also associated with Barrett's oesophagus, an important and
      increasingly diagnosed premalignant lesion. The rate of progression from
      Barrett's oesophagus to cancer is controversial, as is the cost-benefit balance
      of routine endoscopic surveillance of such patients. The development of molecular
      biomarkers to identify Barrett's oesophagus patients with high rates of malignant
      transformation would represent a significant advance.

PMID- 15456467
TI  - Review article: emerging techniques for screening and surveillance in Barrett's
      oesophagus.
AB  - The incidence of oesophageal adenocarcinoma continues to increase in the US and
      the Western world, with the 5-year survival rate for this cancer still being very
      dismal. The diagnosis of Barrett's metaplasia and dysplasia (i.e. screening and
      surveillance) currently requires endoscopy with biopsy of the abnormally
      appearing distal oesophagus. Surveillance endoscopy in patients with Barrett's
      oesophagus relies on the performance of random biopsies from the metaplastic
      segment, with the aim of identifying dysplasia and/or cancer. However, intestinal
      metaplasia and dysplasia are not uniformly distributed within the columnar-lined
      mucosa in the distal oesophagus, and the sensitivity of standard endoscopy with
      biopsy for the detection of these lesions is low. New techniques to improve the
      accuracy of endoscopic diagnosis, as well as to identify patients at high risk
      for neoplasia development, have recently been developed and most are currently
      being evaluated in clinical studies. The results with these techniques, although
      promising, are still preliminary. They hold promise for the improved detection of
      dysplasia and neoplasia at an early stage of development, with a greater chance
      for early treatment, and therefore a greater likelihood of either cure of
      adenocarcinoma or prevention of its development from dysplasia.

PMID- 15456468
TI  - Review article: management of oesophageal adenocarcinoma -- control of acid, bile
      and inflammation in intervention strategies for Barrett's oesophagus.
AB  - Oesophagitis is associated with Barrett's metaplasia in about 10% of individuals.
      The UK has one of the highest world-wide prevalences of Barrett's metaplasia,
      with 1% of adults having the condition, resulting in an incidence of oesophageal
      adenocarcinoma two to three times that seen in either Europe or North America. In
      addition, the conversion rate to cancer in individuals with Barrett's metaplasia
      in UK surveillance programmes is twice that observed in the USA (0.96% per year
      vs. 0.4% per year), lending further support to the notion that the UK is a high
      risk region. The evidence base on what can be achieved with medical therapy to
      reduce the risk of dysplasia or the development of adenocarcinoma needs to be
      strengthened with data from randomized controlled trials, as existing data have
      many limitations. Patients with Barrett's metaplasia respond variably to proton
      pump inhibitor therapy (even high-dose therapy 'normalizes' acid reflux in only
      85% of cases), and symptom control is a poor determinant of the adequacy of
      suppression of acid reflux. Gastro-oesophageal reflux is implicated in the
      pathogenesis of Barrett's metaplasia, and ex vivo and in vitro evidence suggests
      that its attenuation reverses proliferation and biological variables over days,
      and perhaps the metaplastic histology to a degree over years. The effect of
      proton pump inhibitor therapy on cancer risk in the long term is essentially
      unknown. Acid suppressant therapy or anti-reflux surgery on its own does not
      result in the complete regression of the metaplastic epithelium. Bile acids,
      present especially frequently in the refluxate of Barrett's oesophagus patients,
      are also likely to influence the development and persistence of metaplasia.
      Barrett's metaplasia is replaced by a squamous epithelium when acid reflux is
      well controlled and the epithelium is physically destroyed by ablation with argon
      plasma coagulation or photodynamic therapy. These modalities are invasive and are
      not likely to be useful in the routine management of patients with Barrett's
      oesophagus without dysplasia or cancer. Why metaplasia does not fully regress
      once external initiating stimuli are removed is a mystery. There is some evidence
      to implicate a variety of molecules, including cyclo-oxygenase-2, tumour necrosis
      factor-alpha, beta-catenin nuclear translocation and mitogen-activated protein
      kinase signalling, because they are expressed preferentially in metaplastic
      rather than normal or inflamed squamous oesophageal mucosa. The use of non
      steroidal anti-inflammatory drugs, including aspirin, is associated with a
      decreased incidence of oesophageal adenocarcinoma. There is therefore a great
      need for randomized controlled trials to assess the outcomes of such
      chemopreventive therapy in patients with Barrett's metaplasia.

PMID- 15456469
TI  - Review article: anti-reflux surgery and endoluminal therapies.
AB  - In the short term, fundoplication and antisecretory medication are equally
      effective in the management of gastro-oesophageal reflux disease. However, over
      the long term, the fundoplication wrap tends to become loose, and many surgical
      patients continue to take antisecretory medication after surgery. The operation
      is technically complex and takes a long time to learn. Inexperience of the
      individual surgeon is a major factor contributing to the occurrence of
      postsurgical complications. Fundoplication does not prevent the occurrence of
      Barrett's oesophagus nor its progression to oesophageal adenocarcinoma. There is
      no evidence to suggest that the procedure is less costly or more cost-effective
      than long-term maintenance therapy with antisecretory medications, especially if
      surgical failures and postsurgical complications are taken into account.
      Fundoplication represents an alternative to medical therapy in patients with
      gastro-oesophageal reflux disease who cannot or do not want to be on long-term
      maintenance therapy with antisecretory medication. Endoluminal procedures, such
      as radiofrequency ablation, endoscopic suturing and injection at the gastro
      oesophageal junction, work only in mild forms of reflux disease. They fail to
      provide complete relief of reflux symptoms and do not heal erosive oesophagitis.
      All endoluminal procedures would have to undergo major technological improvements
      before they could become comparable with fundoplication or antisecretory therapy.

PMID- 15456470
TI  - Review article: is stringent control of gastric pH useful and practical in GERD?
AB  - As the relative efficacy of therapeutic agents in the treatment of gastro
      oesophageal reflux disease is related to how consistently and completely gastric
      acid secretion is suppressed, intragastric pH monitoring is a useful tool in
      stratifying therapies. If there is no acid in the stomach, there can be none to
      reflux into the oesophagus. Comparative crossover studies have shown consistently
      that once-daily esomeprazole (40 mg) provides more effective and longer lasting
      intragastric acid control than any other proton pump inhibitor currently
      available in healthy subjects and patients with gastro-oesophageal reflux
      disease. However, esomeprazole maintained intragastric pH > 4 for > or = 16 h in
      only about 55% of individuals tested. Thus, if more complete acid suppression is
      desirable, twice-daily proton pump inhibitor therapy may be advantageous. One
      such scenario is in patients with Barrett's metaplasia. Data from the ProGERD
      study suggest that, for each Los Angeles grade of oesophagitis, the healing rate
      for patients with Barrett's metaplasia is 10-30% less than that for non-Barrett's
      patients, being as low as 53% in patients with Los Angeles grade D oesophagitis.
      Also relevant to the Barrett's metaplasia population are studies on the
      oesophageal mucosa, which show that effective acid suppression favours
      differentiation and decreases epithelial cell proliferation. Both considerations
      argue for more intensive gastric acid inhibition than can be achieved with once
      daily therapy, leading to experimentation with twice-daily proton pump inhibitor
      regimens. A randomized, double-blind, three-way crossover study compared
      esomeprazole 40 mg once daily with esomeprazole 20 mg and 40 mg twice daily and
      found that both twice-daily regimens were superior, maintaining intragastric pH >
      4 for 73%[95% confidence interval (CI), 67-79%] and 80% (95% CI, 75-86%) of the
      day, respectively, compared with 59% (95% CI, 54-65%) of the day with
      esomeprazole 40 mg once daily, arguing that a twice-daily regimen may be the
      preferred strategy for patients with Barrett's metaplasia.

PMID- 15456472
TI  - Clinical strategies -- interactive case discussions.
AB  - Interactive case discussions held during the symposium illustrate the practical
      challenges and dilemmas faced in the management of Barrett's oesophagus. Opinions
      of the faculty and audience varied widely on how proton pump inhibitor therapy
      should be used, especially in patients with short-segment Barrett's oesophagus.
      The therapeutic goal that received most support was to achieve sufficient acid
      control to keep the patient symptom free and heal any oesophagitis. At the same
      time, the patient should be reassured of the low risk associated with the
      endoscopic findings. When long-segment Barrett's oesophagus is detected, it
      should be assessed in detail, with targeted biopsy of any irregular-surfaced
      metaplastic mucosa and four quadrant biopsies every 2 cm, to diagnose intestinal
      metaplasia and to screen for dysplasia or cancer. Repeat endoscopy and biopsy may
      be appropriate to achieve a sensitive initial assessment because of potential
      sampling error. Proton pump inhibitor therapy, often twice daily, was considered
      a requirement for most cases of long-segment Barrett's oesophagus. There was
      disagreement over the role of surveillance, although proponents viewed it as
      worthwhile even in patients at low risk for the development of adenocarcinoma,
      mainly for medico-legal reasons. Endoscopic mucosal resection was seen to be
      appropriate in carefully selected patients with high-grade dysplasia, depending
      on factors such as age and comorbidity, the extent of high-grade dysplasia,
      findings on endoscopic ultrasound and the length of Barrett's oesophagus.

PMID- 15456473
TI  - Review article: what I do now to manage adenocarcinoma risk, and what I may be
      doing in 10 years' time.
AB  - This article summarizes the present recommendations for the screening,
      surveillance and treatment of Barrett's oesophagus, and identifies those areas in
      which change seems likely within the next decade. As a result of economic
      constraints and emerging data on ethnic variations in the frequency of Barrett's
      oesophagus, future screening programmes will probably focus on those individuals
      most likely to develop Barrett's adenocarcinomas: older white men whose gastro
      oesophageal reflux symptoms are of long duration. The present surveillance
      strategy for patients with Barrett's oesophagus relies heavily on random biopsy
      sampling of the oesophagus to find dysplasia. In the future, biomarkers other
      than dysplasia may be used to identify patients at high risk for carcinogenesis,
      and physicians may use endoscopic techniques, such as fluorescence spectroscopy,
      to identify areas of dysplasia for biopsy sampling. Indirect evidence suggests
      that super-aggressive antisecretory therapy and treatment with non-steroidal anti
      inflammatory drugs may reduce the risk of cancer in Barrett's oesophagus. Well
      designed prospective studies will be needed to determine whether these treatments
      have sufficient efficacy in cancer prophylaxis to justify the large numbers
      needed to treat. Finally, recent data are reviewed, which suggest that the gastro
      oesophageal junction is exposed repeatedly to concentrated acid and to
      potentially genotoxic concentrations of nitric oxide generated from dietary
      nitrate. Future studies on carcinogenesis in Barrett's oesophagus may well focus
      on the combined roles of nitric oxide and gastric acid.

PMID- 15456474
TI  - Recollections of the development of flow devices for studying mechanisms of
      hemostasis and thrombosis in flowing whole blood.

PMID- 15456475
TI  - Recombinant factor VIIa: a general hemostatic agent? Yes.

PMID- 15456476
TI  - Recombinant factor VIIa: a general hemostatic agent? Not yet.

PMID- 15456477
TI  - Thrombosis and recombinant factor VIIa.

PMID- 15456478
TI  - Comparative thrombotic event incidence after infusion of recombinant factor VIIa
      versus factor VIII inhibitor bypass activity.
AB  - Thrombosis is a rare but well-recognized potential complication of Factor VIII
      Inhibitor Bypass Activity (FEIBA) infusion. Recombinant factor VIIa (rFVIIa) is
      increasingly used as an alternative to FEIBA; however, the thrombotic safety
      profile of rFVIIa remains incompletely characterized. To determine the incidence
      rates of thrombotic adverse events (AEs) after infusion of rFVIIa and FEIBA. Data
      from the MedWatch pharmacovigilance program of the US Food and Drug
      Administration, as supplemented by published case reports, were used in
      conjunction with estimated numbers of infusions available from manufacturers to
      assess comparative incidence of thrombotic AEs in patients receiving rFVIIa or
      FEIBA in the period from April 1999 through June 2002. Reported thrombotic AEs
      were rare, with incidence rates of 24.6 per 10(5) infusions (CI, 19.1-31.2 per
      10(5) infusions) for rFVIIa and 8.24 per 10(5) infusions (CI, 4.71-13.4 per 10(5)
      infusions) for FEIBA. Thrombotic AEs were significantly more frequent in rFVIIa
      than FEIBA recipients (incidence rate ratio, 2.98; CI, 1.71-5.52). The most
      commonly documented single type of thrombotic AE after rFVIIa infusion was
      cerebrovascular thrombosis, while myocardial infarction was the most frequent
      type in patients receiving FEIBA. Contrasting AE reporting patterns between
      rFVIIa and FEIBA may have contributed to the observed difference in thrombotic
      event incidence. Nevertheless, this comprehensive pharmacovigilance assessment
      does not support superior thrombotic safety of rFVIIa and suggests that
      thrombotic AE risk may be higher in rFVIIa than FEIBA recipients.

PMID- 15456479
TI  - Do platelets synthesize factor XI?

PMID- 15456480
TI  - Real-time quantitative PCR analysis of factor XI mRNA variants in human
      platelets.
AB  - Coagulation factor XI (FXI) plays an essential role in blood coagulation. A
      deficiency of FXI is an unusual hemorrhagic diathesis in that the bleeding
      tendency can be highly variable, ranging from severe deficiencies with no
      symptoms to mild and moderate deficiencies requiring multiple blood transfusions
      for hemorrhages. This variability in bleeding has been attributed to a number of
      factors including the presence of a novel form of FXI associated with platelets,
      which ameliorates the bleeding in some cases of FXI deficiency. However, the
      nature of this platelet FXI molecule is controversial. Hsu et al. (J Biol Chem
      1998; 273: 13787-93) suggest that it is a product of normal FXI - but lacking
      exon V whilst Martincic et al. (Blood 1999; 94: 3397-404) were unable to detect
      this alternatively spliced variant using RT-PCR. In order to resolve this
      controversy, we have employed the highly sensitive technique of real-time
      quantitative RT-PCR using RNA isolated from FXI-deficient patients. Our results
      indicate that the platelets of both normal and FXI deficient individuals contain
      FXI mRNA that is identical to the mRNA found in liver. An exon V deleted splice
      variant was not detected. Thus the FXI message is not alternatively spliced in
      platelets and therefore would not be able to produce an unusual FXI protein.

PMID- 15456481
TI  - Slippery criteria for von Willebrand disease type 1.

PMID- 15456482
TI  - Is the assessment of von Willebrand disease prevalence an achievable challenge?
      The example of the French Basque Country where blood group O and factor XI
      deficiency are highly prevalent.
AB  - The diagnosis of type I von Willebrand disease (VWD) is not straightforward
      because of the absence of a single clear-cut biological criteria and the
      interference of several acquired conditions on phenotype expression. We
      illustrate here this challenge with the French Basque population characterised by
      a marked high frequency in both blood group O and factor XI deficiency. From this
      example one may question the validity of epidemiological studies reporting on VWD
      prevalence.

PMID- 15456483
TI  - Does the genotype predict the phenotype? Evaluations of the hemostatic proteome.
AB  - In this review, the complexity arising from the heterogeneity of the human
      hemostatic proteome is introduced and discussed with respect to impact on the
      diagnosis, prophylaxis and therapeutic interventions in thrombotic and
      hemorrhagic diseases. In the 'healthy' population, coagulation factor levels
      extend over a 2-4-fold range in concentration. In addition, the qualitative
      performance of these proteins is governed by many molecular events which are
      influenced both by genetic instructions which influence post-translational
      modification and by environmental processes that alter coagulation proteins
      during circulation. As a consequence, the stimulus-response coupling which
      follows tissue factor presentation to blood and the subsequent expression of
      thrombin activity is highly variable even in the 'normal' population. The
      consequences of this molecular heterogeneity and its potential influence on the
      diagnosis, prophylaxis and ultimate therapy of coagulation diseases are
      illustrated. It is the intention of the authors to be provocative; encouraging
      further investigations to understand the clinical significance of the
      heterogeneity of the human hemostatic proteome.

PMID- 15456484
TI  - Factor VIIa replacement therapy in factor VII deficiency.
AB  - Factor (F)VII deficiency is an autosomal recessive disorder for which a
      replacement therapy is not universally available; recombinant FVIIa has been
      utilized as a therapeutic substitute. As FVII competes with FVIIa for binding to
      tissue factor in initiating the extrinsic pathway of blood coagulation, a lower
      dose of FVIIa replacement in cross-reacting material-negative (CRM-) individuals
      can achieve hemostasis. Three coagulation models (computational, synthetic and in
      vitro whole blood) were used to predict the FVIIa levels needed to provide
      apparent hemostasis in a non-bleeding state. Our whole blood results show that a
      'normalized' coagulation profile for FVII-deficient individuals has an initiation
      phase that ends at 5.8 +/- 0.5 min (clot time) and the propagation phase of
      thrombin generation (thrombin-antithrombin III) yields a maximum concentration of
      380 +/- 29 nmol L(-1). When CRM- FVII-deficient subjects were infused with a
      prophylactic dose of 23 micro g kg(-1) of recombinant FVIIa, 6-8 h postinfusion
      resulted in a comparable normalized whole blood profile. This FVIIa concentration
      (0.3-0.7 nmol L(-1)/equivalent dose: 0.8-1.8 micro g kg(-1)) is approximately
      1/10 that currently used in treating FVII-deficient individuals and suggests that
      therapies should be altered relative to the concentration of the FVII zymogen.

PMID- 15456485
TI  - Phase I study of a novel recombinant human soluble thrombomodulin, ART-123.
AB  - BACKGROUND: Anticoagulants are often given for extended periods of time to
      patients at high risk for venous thromboembolism, such as after orthopedic
      surgery. Daily subcutaneous (sc) injections can be inconvenient to the patient. A
      long-acting anticoagulant requiring less frequent dosing could make treatment
      more acceptable. Thrombomodulin is a natural anticoagulant that activates protein
      C, which leads to inactivation of factor (F)Va and FVIIIa and decreased thrombin
      formation. Recombinant human thrombomodulin is a novel anticoagulant with a long
      half-life in animal models. METHODS AND RESULTS: This phase I study examined
      pharmacokinetics, pharmacodynamics, and safety of recombinant human soluble
      thrombomodulin (ART-123) after administration of doses between 0.02 and 0.06 mg
      kg(-1) body weight intravenously (iv), and between 0.02 and 0.45 mg kg(-1) sc in
      55 healthy volunteers. The plasma half-life was 2-3 days after sc injection of
      various single doses. Plasma ART-123 levels estimated to be needed for prevention
      of thrombus formation in humans were maintained for at least 6 days after single
      sc injection of 0.30 and 0.45 mg kg(-1) ART-123. Antithrombotic activity with
      these doses was demonstrated by achieving prothrombinase inhibition of more than
      80% for more than 6 days after administration. No major bleeding occurred.
      Pharmacodynamic modeling revealed that adequate antithrombotic ART-123 levels can
      be achieved for 6 days with one dose of 0.45 mg kg(-1) ART-123, and for 12 days
      with 2 doses of 0.30 mg kg(-1), given 5 days apart. CONCLUSIONS: Recombinant
      human soluble thrombomodulin (ART-123) has a long half-life after sc injection
      and is well tolerated, making it a suitable agent to be tested in clinical
      thromboprophylaxis trials.

PMID- 15456486
TI  - Bilateral vs. ipsilateral venography as the primary efficacy outcome measure in
      thromboprophylaxis clinical trials: a systematic review.
AB  - Contrast venography, in combination with symptomatic venous thromboembolism
      (VTE), is the standard efficacy outcome measure in clinical trials of
      thromboprophylaxis in major orthopedic surgery. It is uncertain whether
      performing bilateral venography offers any real advantage over venography of the
      operated leg alone. This study was undertaken to determine the risk of isolated
      contralateral deep vein thrombosis (DVT) following major orthopedic surgery and
      to evaluate whether bilateral venography, rather than venography on the operated
      leg alone, offers any gain in DVT detection and, thereby, improves efficiency in
      clinical study design. A systematic review of prospective studies that reported
      DVT incidence as the primary efficacy outcome based on mandatory bilateral
      venography in patients undergoing elective hip or knee arthroplasty or hip
      fracture repair was conducted. Based on the use of bilateral venography as a
      primary efficacy outcome measure, the incidence of any DVT is 16.7% following
      total hip replacement, 18.8% after hip fracture repair, and 33.8% after total
      knee replacement. While DVT risk in the operated leg varies depending on the type
      of surgery, the risk of isolated DVT in the non-operated leg is approximately 4%
      to 5% in all three procedures. By increasing the detection of any DVT, the use of
      bilateral venography reduces required sample size by 16% to 25% compared to
      ipsilateral venography. In clinical trials evaluating the efficacy of
      thromboprophylaxis in major orthopedic surgery, bilateral venography reduces the
      risk of undiagnosed DVT in the non-operated leg and improves the efficiency of
      study design by substantially reducing the sample size requirement.

PMID- 15456487
TI  - The risk of a venous thrombotic event in lung cancer patients: higher risk for
      adenocarcinoma than squamous cell carcinoma.
AB  - BACKGROUND: Only limited data on the incidence of venous thrombosis in different
      types of malignancy are available. Patients with adenocarcinoma are believed to
      have the highest risk of developing venous thrombosis. OBJECTIVES: To study the
      incidence of thrombosis in patients with lung cancer, with an emphasis on the
      comparison between adenocarcinoma and squamous cell carcinoma, we have performed
      a cohort study of patients with non-small-cell lung cancer. In addition the risk
      associated with treatment and extent of disease was assessed. PATIENTS/METHODS: A
      total of 537 patients with a first diagnosis of lung carcinoma were included.
      Patient and tumor characteristics as well as venous thrombotic events were
      recorded from the medical records and from the Anticoagulation Clinic. RESULTS:
      Thrombotic risk in lung cancer patients was 20-fold higher than in the general
      population (standardized morbidity ratio (SMR): 20.0 (14.6-27.4). In the group of
      patients with squamous cell cancer we found 10 (10/258) cases (incidence: 21.2
      per 1000 years) of venous thrombosis whereas in the group of patients with
      adenocarcinoma 14 (14/133) cases (incidence: 66.7 per 1000 years) occurred. The
      crude adjusted hazard ratio was 3.1 (95% CI: 1.4-6.9). The risk increased during
      chemotherapy and radiotherapy and in the presence of metastases. CONCLUSIONS: The
      risk of venous thrombosis in lung cancer patients is increased 20-fold compared
      to the general population. Patients with adenocarcinoma have a higher risk than
      patients squamous cell carcinoma. During chemotherapy or radiotherapy and in the
      presence of metastases the risk is even higher.

PMID- 15456488
TI  - Direct anticoagulant activity of protein S-C4b binding protein complex in Heerlen
      heterozygotes and normals.
AB  - BACKGROUND: Plasma protein S normally circulates free (40%) or complexed with C4b
      binding protein (PS-C4BP); only free protein S is a cofactor for activated
      protein C during factor (F) Va inactivation. Protein S-Heerlen lacks a
      carbohydrate group, leading to low plasma free protein S levels, but normal
      levels of PS-C4BP. OBJECTIVES: Because protein S-Heerlen is not associated with
      thrombosis, we investigated whether PS-C4BP is directly anticoagulant in plasma
      and whether PS-Heerlen-C4BP has enhanced direct anticoagulant activity. METHODS:
      An assay for protein S direct activity was applied to Heerlen-heterozygous
      plasmas. Free and complexed protein S were repeatedly isolated from normal and
      Heerlen-heterozygous plasmas and tested for direct anticoagulant activity in
      prothrombinase assays and in plasma. RESULTS: Heerlen-heterozygous plasmas were
      deficient in free and total protein S antigen but had normal to high protein S
      direct anticoagulant activity. Purified Heerlen-heterozygous PS-C4BP was 7-fold
      more potent than normal PS-C4BP in inhibiting full prothrombinase activity, and
      22-fold more potent in inhibiting prothrombin activation in the absence of FVa;
      it also specifically prolonged plasma clotting times 14-fold more than normal PS
      C4BP. Heerlen-heterozygous PS-C4BP did not compete for limiting phospholipids any
      better than normal PS-C4BP. However, ligand blots and surface plasmon resonance
      studies showed that Heerlen-heterozygous PS-C4BP bound more avidly to FXa than
      did normal PS-C4BP (apparent Kd = 4.3 nm vs. 82 nm). CONCLUSIONS: Plasma-derived
      PS-C4BP has direct anticoagulant activity in plasma and in purified systems.
      Enhanced direct activity of PS-Heerlen-C4BP may compensate for low free protein S
      levels and low cofactor activity in individuals with protein S-Heerlen.

PMID- 15456489
TI  - Characterization of mutations causing factor VII deficiency in 61 unrelated
      Israeli patients.
AB  - Inherited factor (F)VII deficiency is rare in most populations but relatively
      common in Israel. The aim of this study was to characterize the molecular and
      functional defect in unrelated Israeli patients with FVII deficiency. Mutations
      were identified by direct sequencing of PCR-amplified genomic DNA fragments.
      Selected mutations were expressed in baby hamster kidney (BHK) cells and tested
      for binding to tissue factor (TF), activation by FXa and activation of FX. In 61
      patients with FVII deficiency, the causative mutation in the FVII gene was
      discerned. The predominant mutation found in this and a previously reported
      cohort of 27 unrelated patients in Israel was Ala244Val substitution; of 121
      independent mutant alleles defined in all 88 patients ascertained in Israel, 102
      (84%) bore this alteration. Eleven additional mutations were identified of which
      one, Cys22Arg, is novel. Expression of the mutations in BHK cells revealed that
      four (Ala244Val, 11128delC, Leu300Pro and Cys22Arg) were cross-reacting material
      (CRM)- negative, and three (Ala294Val, Cys310Phe and Phe24del) were CRM-positive.
      As predicted by modeling, we observed no binding to TF of FVII Phe24del,
      diminished binding of FVII Cys310Phe and normal binding of FVII Ala294Val. The
      main defect of FVII Ala294Val was its inability to activate FX in the presence of
      TF. Coexpression of Ala294Val and Arg353Gln, a polymorphism known to affect FVII
      secretion, did not reveal an additive effect on FVII secretion, while
      coexpression of Ala244Val and Arg353Gln did yield an additive effect.

PMID- 15456490
TI  - Severe factor XI deficiency caused by a Gly555 to Glu mutation (factor XI
      Glu555): a cross-reactive material positive variant defective in factor IX
      activation.
AB  - During normal hemostasis, the coagulation protease factor (F)XIa activates FIX.
      Hereditary deficiency of the FXIa precursor, FXI, is usually associated with
      reduced FXI protein in plasma, and circulating dysfunctional FXI variants are
      rare. We identified a patient with < 1% normal plasma FXI activity and normal
      levels of FXI antigen, who is homozygous for a FXI Gly555 to Glu substitution.
      Gly555 is two amino acids N-terminal to the protease active site serine residue,
      and is highly conserved among serine proteases. Recombinant FXI-Glu555 is
      activated normally by FXIIa and thrombin, and FXIa-Glu555 binds activated factor
      IX similarly to wild type FXIa (FXIa(WT)). When compared with FXIa(WT), FXIa
      Glu555 activates factor IX at a greatly reduced rate ( approximately 400-fold),
      and is resistant to inhibition by antithrombin. Interestingly, FXIa(WT) and FXIa
      Glu555 cleave the small tripeptide substrate S-2366 with comparable k(cat)s.
      Modeling indicates that the side chain of Glu555 significantly alters the
      electrostatic charge around the active site, and would sterically interfere with
      the interaction between the FXIa S2' site and the P2' residues on factor IX and
      antithrombin. FXI-Glu555 is the first reported example of a naturally occurring
      FXI variant with a significant defect in FIX activation.

PMID- 15456491
TI  - Seven novel mutations in the factor XIII A-subunit gene causing hereditary factor
      XIII deficiency in 10 unrelated families.
AB  - BACKGROUND: Hereditary factor (F)XIII deficiency is a rare bleeding disorder
      mostly due to mutations in FXIII A subunit. OBJECTIVES: We studied the molecular
      basis of FXIII deficiency in patients from 10 unrelated families originating from
      Israel, India and Tunisia. METHODS: Exons 2-15 of genomic DNA consisting of
      coding regions and intron/exon boundaries were amplified and sequenced.
      Structural analysis of the mutations was undertaken by computer modeling.
      RESULTS: Seven novel mutations were identified in the FXIIIA gene. The propositus
      from the Ethiopian-Jewish family was found to be a compound heterozygote for two
      novel mutations: a 10-bp deletion in exon 12 at nucleotides 1652-1661 (followed
      by 22 altered amino acids and termination codon) and Ala318Val mutation. The
      propositus of the Tunisian family was homozygous for C insertion after nucleotide
      863 within a stretch of six cytosines of exon 7. This insertion results in
      generation of eight altered amino acids followed by a termination codon
      downstream. The propositus from Indian-Jewish origin was found to be homozygous
      for G to T substitution at IVS 11 [+1] resulting in skipping of exons 10 and 11.
      In addition to the Ala318Val mutation, three of the novel mutations identified
      are missense mutations: Arg260Leu, Thr398Asn and Gly210Arg each occurring in a
      homozygous state in an Israeli-Arab and two Indian families, respectively.
      CONCLUSIONS: Structure-function correlation analysis by computer modeling of the
      new missense mutations predicted that Gly210Arg will cause protein misfolding,
      Ala318Val and Thr398Asn will interfere with the catalytic process or protein
      stability, and Arg260Leu will impair dimerization.

PMID- 15456492
TI  - A central role for plasminogen in the inflammatory response to biomaterials.
AB  - The inflammatory response to implanted biomaterials severely limits their
      deployment in patients. Plasminogen has been shown to play a central role in cell
      migration, and therefore could regulate this inflammatory response. We sought to
      determine if plasminogen influences recruitment of inflammatory cells to a
      biomaterial implanted into plasminogen-deficient (Plg(-/-)) mice. Small disks of
      polyethylene terephthalate, a material used in vascular grafts, were surgically
      implanted into the peritoneum of wild-type and Plg(-/-) mice. Recruitment of
      neutrophils and monocytes/macrophages into the peritoneum and onto the disks was
      measured, primarily at 18 h. Monocyte/macrophage recruitment was markedly blunted
      in Plg(-/-) mice compared with wild-type mice. Unexpectedly, neutrophil
      recruitment was also markedly decreased in the Plg(-/-) mice. While recruitment
      of leukocytes into the peritoneum was plasminogen-dependent, the adhesion of the
      emigrating cells to the implants was not. In contrast, adhesion but not
      recruitment was reduced in fibrinogen-deficient mice. Reconstitution of Plg(-/-)
      mice with intravenous or intraperitoneal plasminogen differentially restored
      monocyte/macrophage and neutrophil recruitment. Tranexamic acid, an inhibitor of
      the lysine binding sites of plasminogen, suppressed leukocyte recruitment in wild
      type mice, but aprotinin, a plasmin inhibitor, did not. Plasminogen exerts a
      marked influence on both neutrophil and monocyte/macrophage recruitment to
      implanted biomaterials. This role is distinct from that of fibrinogen, and the
      two inflammatory cell types use plasminogen in different ways. Plasminogen
      represents a therapeutic target for controlling the inflammatory response to
      implanted materials.

PMID- 15456493
TI  - Fibrin stimulates platelets to increase factor VIIIa binding site expression.
AB  - Factor (F)VIII functions as an enzymatic cofactor on the membranes of stimulated
      platelets. However, thrombin stimulates platelets to express only a small number
      of binding sites for FVIII. We wished to determine whether molecules that are
      likely to be present in a developing thrombus stimulate platelets to up-regulate
      FVIII binding site expression. Flow cytometry was utilized to measure binding of
      fluorescein-labeled FVIIIa to activated platelets and a FXase assay was utilized
      to measure platelet-dependent function. Various agonists as well as normal and
      mutant fibrinogens and fibrin were evaluated as co-stimuli. Thrombin-stimulated
      platelets expressed 214 +/- 67 binding sites for thrombin-activated FVIII
      (FVIIIa) and none of the established soluble agonists enhanced binding site
      exposure. However, the presence of 5 micro g mL(-1) fibrin increased the number
      of FVIIIa binding sites/platelet three- to eight-fold (1470 +/- 130, range 600
      1800) with a parallel increase in platelet-based FXase assay. Binding site up
      regulation was not stimulated by fibrinogen and was blocked by inhibitors of
      GPIIbIIIa. Mutant fibrin lacking the gamma-chain C-terminal four residues was
      ineffective while fibrin with altered RGD sequences did stimulate expression of
      FVIIIa binding sites indicating that co-stimulation is mediated by the fibrin
      gamma-chain termini. Fibrin-enhanced expression of FVIIIa binding sites was not
      supported by D364H fibrin, which does not aggregate normally, and was blocked by
      the GPRP peptide, which inhibits fibrin polymerization. Polymerized fibrin can
      function as a platelet co-stimulus, up-regulating expression of binding sites for
      FVIIIa.

PMID- 15456494
TI  - Recombinant human factor VIIa (rFVIIa) can activate factor FIX on activated
      platelets.
AB  - The studies reported here show that factor (F)VIIa can activate factor (F)IX on
      activated platelets in the absence of tissue factor. Both FIX and FIXa bind to
      the activated platelet surface with a K(d) of 8 nM and 2 nM, respectively. With
      factor (F)VIIIa, FIXa binds more tightly to platelets (K(d) 0.6 nM). At rFVIIa
      concentrations < 100 nm, no direct binding to the activated platelet surface can
      be detected with electrophoretic light scattering. However, in the presence of
      FIX, rFVIIa binding to platelets at concentrations as low as 10 nm rFVIIa can be
      detected. This is reflected by a decrease in the FIX K(d) from 8 to 1.6 nM. When
      rFVIIa is added to activated platelets in the presence of both FIX and FVIIIa,
      the K(d) for FIX decreases to 0.6, suggesting that rFVIIa activates FIX on the
      surface of activated platelets in the absence of tissue factor. The activation of
      FIX by FVIIa on activated platelets can also be demonstrated by a functional
      assay for FIXa. These data show that pharmacological doses of rFVIIa result in
      the direct activation of FIX by rFVIIa to form additional tenase complexes
      ultimately resulting in improved thrombin generation. These results may explain,
      at least in part, the mechanism of action of rFVIIa in hemorrhagic conditions
      seen in otherwise normal patients who develop an acquired coagulopathy due to
      trauma, surgery or a variety of other events in which rFVIIa has been found to be
      effective.

PMID- 15456495
TI  - Evaluation of the role of platelet integrins in fibronectin-dependent spreading
      and adhesion.
AB  - BACKGROUND: Recent studies have shown that platelet adhesion and subsequent
      aggregation can occur in vivo in the absence of the two principal platelets
      adhesive ligands, von Willebrand factor and fibrinogen. These results highlight a
      possible role for fibronectin in supporting thrombus formation. OBJECTIVE AND
      METHODS: To evaluate the platelet integrins and subsequent activation pathways
      associated with fibronectin-dependent platelet adhesion utilizing both human and
      murine platelets. RESULTS: Platelets can adhere to fibronectin via the integrin
      alpha(IIb)beta(3), leading to formation of lamellipodia. This is mediated through
      an interaction with the tenth type III domain in fibronectin. Spreading on
      fibronectin promotes alpha(IIb)beta(3)-mediated Ca(2+) mobilization and tyrosine
      phosphorylation of focal adhesion kinase and phospholipase C gamma2. In contrast,
      studies with blocking antibodies and mice demonstrate that alpha(5)beta(1) and
      alpha(v)beta(3) support adhesion and promote formation of filopodia but not
      lamellipodia or tyrosine phosphorylation of these proteins. Further, neither
      alpha(5)beta(1) nor alpha(v)beta(3) is able to induce formation of lamellipodia
      in the presence of platelets agonists, such as collagen-related-peptide (CRP).
      CONCLUSIONS: These observations demonstrate that integrins alpha(5)beta(1) and
      alpha(v)beta(3) support platelet adhesion and the generation of filopodia but
      that, in contrast to the integrin alpha(IIb)beta(3), are unable to promote
      formation of lamellipodia.

PMID- 15456496
TI  - The impact of vitamin K-dependent factor depletion by warfarin on platelet-rich
      thrombosis after deep arterial injury.
AB  - Although the central role of thrombin in arterial thrombosis is well established,
      the efficacy of vitamin K-dependent factor depletion by warfarin at preventing
      this process has not been established. To assess the efficacy of warfarin in the
      prevention of arterial thrombosis, two intensities of anticoagulation were
      compared in a well-characterized porcine model of carotid angioplasty. For 10
      days prior to angioplasty, pigs received either high-dose warfarin (n = 9), low
      dose warfarin plus aspirin (n = 9), or control tablets (n = 10). Injured arteries
      were assessed for (111)In-platelet ( x 10(6) cm(-2)) and (125)I-fibrin(ogen)
      (molecules x 10(12) cm(-2)) deposition and the incidence of macroscopic thrombus.
      Platelet (30 +/- 7 vs. 332 +/- 137; P = 0.001) and fibrinogen (156 +/- 17 vs. 365
      +/- 90; P < 0.05) deposition were significantly reduced in animals receiving high
      intensity warfarin whereas low-intensity warfarin/ASA (520 +/- 240 and 1193 +/-
      638) was similar to control (P =NS). At the time of angioplasty, the PT-INR and
      vitamin K-dependent factors varied over a broad range. The greatest reduction of
      platelet and fibrinogen deposition occurred as the PT-INR increased from 1.0 to
      2.2. Increasing the PT-INR beyond 3.0 resulted in little, if any, incremental
      reduction of either platelet or fibrinogen deposition. Macroscopic thrombus was
      abolished at PT-INR > 2.2. Despite a broad range of vitamin K factor activities,
      no single factor was predictive of either platelet or fibrinogen deposition.
      Warfarin at PT-INR > 2.2 effectively eliminates thrombosis following deep
      arterial injury. Arterial thrombosis correlates poorly with any single vitamin K
      dependent factor but rather appears to be a function of the entire extrinsic
      coagulation pathway as measured by the PT-INR.

PMID- 15456497
TI  - Measuring circulating cell-derived microparticles.

PMID- 15456504
TI  - Is there a high thrombosis rate associated with recombinant factor VIIa use in
      intractable hemorrhage in Australia?

PMID- 15456505
TI  - Successful treatment of cyclophosphamide induced intractable hemorrhagic cystitis
      with recombinant FVIIa (NovoSeven) after allogenic bone marrow transplantation.

PMID- 15456506
TI  - Hemophilia replacement products, clinical trials: inhibitors and pharmacokinetics
      can they be done?

PMID- 15456507
TI  - Diagnosing pulmonary embolism in pregnancy: rationalizing fetal radiation
      exposure in radiological procedures.

PMID- 15456508
TI  - Is venous thromboembolism more frequent in patients with obstructive sleep apnea
      syndrome?

PMID- 15456509
TI  - Proposals for the measurement of anti-beta2-glycoprotein I antibodies.
      Standardization group of the European Forum on Antiphospholipid Antibodies.

PMID- 15456510
TI  - Accuracy of D-dimer/fibrinogen ratio to predict pulmonary embolism: a prospective
      diagnostic study - a rebuttal.

PMID- 15456512
TI  - Control and maintenance of mammalian cell size.
AB  - BACKGROUND: Conlon and Raff propose that mammalian cells grow linearly during the
      division cycle. According to Conlon and Raff, cells growing linearly do not need
      a size checkpoint to maintain a constant distribution of cell sizes. If there is
      no cell-size-control system, then exponential growth is not allowed, as
      exponential growth, according to Conlon and Raff, would require a cell-size
      control system. DISCUSSION: A reexamination of the model and experiments of
      Conlon and Raff indicates that exponential growth is fully compatible with cell
      size maintenance, and that mammalian cells have a system to regulate and maintain
      cell size that is related to the process of S-phase initiation. Mammalian cell
      size control and its relationship to growth rate-faster growing cells are larger
      than slower growing cells-is explained by the initiation of S phase occurring at
      a relatively constant cell size coupled with relatively invariant S- and G2-phase
      times as interdivision time varies. SUMMARY: This view of the mammalian cell
      cycle, the continuum model, explains the mass growth pattern during the division
      cycle, size maintenance, size determination, and the kinetics of cell-size change
      following a shift-up from slow to rapid growth.

PMID- 15456513
TI  - Relationship between CRP and hypofibrinolysis: Is this a possible mechanism to
      explain the association between CRP and outcome in critically ill patients?
AB  - BACKGROUND-: Endothelial cell dysfunction may be implicated in the development of
      multiple organ failure (MOF) by a number of mechanisms. Among these, altered
      fibrinolysis promotes fibrin deposition, which may create microvascular
      alterations during inflammation. Elevated concentrations of C-reactive protein
      (CRP), especially when these persist over time, are correlated with an increased
      risk of MOF and death. CRP may inhibit fibrinolysis by inducing plasminogen
      activator inhibitor-1 (PAI-1) release from human aortic endothelial cells.
      Moreover, the administration of recombinant CRP in volunteers may increase
      circulating PAI-1 levels.In this study, we tested the hypothesis that CRP is
      associated with hypofibrinolysis in intensive care patients with and without
      sepsis. METHODS-: We studied the association of inflammation and abnormal
      fibrinolysis in intensive care unit (ICU) patients with (n = 11) and without (n =
      21) sepsis. The inflammatory response was assessed by serum concentration of C
      reactive protein (CRP), a marker of the acute phase reaction, which increase
      rapidly in the inflammatory response, and the plasma fibrinolytic capacity was
      evaluated by the Euglobulin Clot Lysis Time (ECLT), determined by a new semi
      automatic method. RESULTS-: ECLT was significantly higher in septic than non
      septic patients (1104 +/- 439 vs 665 +/- 275 min; p = 0.002) and was
      significantly correlated with CRP concentration (R2 = 0.45; p < 0.001). In a
      multivariate analysis, CRP was the strongest predictor of ECLT (R2 = 0.51, F =
      25.6, p < 0.001). In addition, the overall ICU length of stay was significantly
      correlated with CRP (R2 = 0.264, p = 0.003) and ECLT (R2 = 0.259, p = 0.003).
      CONCLUSION-: In critically ill patients a significant correlation thus exists
      between plasma fibrinolytic capacity and serum CRP levels. Our data were obtained
      in the first 24 hours of ICU admission or of sepsis, thus, the relation between
      CRP and hypofibrinolysis appeared very quickly. This finding is compatible with a
      link between inflammation and abnormal fibrinolysis, and may explain the negative
      prognostic value of CRP in critically ill patients.

PMID- 15456514
TI  - Distance, rurality and the need for care: access to health services in South West
      England.
AB  - BACKGROUND: This paper explores the geographical accessibility of health services
      in urban and rural areas of the South West of England, comparing two measures of
      geographical access and characterising the areas most remote from
      hospitals.Straight-line distance and drive-time to the nearest general practice
      (GP) and acute hospital (DGH) were calculated for postcodes and aggregated to
      1991 Census wards. The correlation between the two measures was used to identify
      wards where straight-line distance was not an accurate predictor of drive-time.
      Wards over 25 km from a DGH were classified as 'remote', and characterised in
      terms of rurality, deprivation, age structure and health status of the
      population. RESULTS: The access measures were highly correlated (r2>0.93). The
      greatest differences were found in coastal and rural wards of the far South West.
      Median straight-line distance to GPs was 1 km (IQR = 0.6-2 km) and to DGHs, 12 km
      (IQR = 5-19 km). Deprivation and rates of premature limiting long term illness
      were raised in areas most distant from hospitals, but there was no evidence of
      higher premature mortality rates. Half of the wards remote from a DGH were not
      classed as rural by the Office for National Statistics. Almost a quarter of
      households in the wards furthest from hospitals had no car, and the proportion of
      households with access to two or more cars fell in the most remote areas.
      CONCLUSION: Drive-time is a more accurate measure of access for peripheral and
      rural areas. Geographical access to health services, especially GPs, is good, but
      remoteness affects both rural and urban areas: studies concentrating purely on
      rural areas may underestimate geographical barriers to accessing health care. A
      sizeable minority of households still had no car in 1991, and few had more than
      one car, particularly in areas very close to and very distant from hospitals.
      Better measures of geographical access, which integrate public and private
      transport availability with distance and travel time, are required if an accurate
      reflection of the experience those without their own transport is to be obtained.

PMID- 15456515
TI  - Personalized versus non-personalized computerized decision support system to
      increase therapeutic quality control of oral anticoagulant therapy: an
      alternating time series analysis.
AB  - BACKGROUND: The quality control of oral anticoagulant therapy (OAT) during the
      initiation and maintenance treatment is generally poor. Physicians' ordering of
      OAT (especially fluindione and warfarin) can be improved by dose adjustment
      algorithms, taking into account the results of International Normalized Ratio
      (INR). Reminders at the point of care, computerized or not, have been
      demonstrated to be effective in changing physicians prescription
      behavior.However, few studies have addressed the benefit of personalized
      reminders versus non personalized reminders, whereas the personalized reminders
      require more development to access patient record data and integrate with the
      computerized physician order entry system. The Hospital Information System of
      George Pompidou European Hospital integrates an electronic medical record, lab
      test and drugs order entry system. This system allows to evaluate such reminders
      and to consider their implementation for routine use as well as the continuous
      evaluation of their impact on medical practice quality indicators. The objective
      of this study is to evaluate the impact of two types of reminders on
      overtreatment by oral anticoagulant: a simple reminder of text formatted dose
      adjustment table and a personalized recommendation for oral anticoagulant dose
      and next date of INR control, adapted to patient data. Both types of reminders
      appear to the physician at the moment of drug ordering.

PMID- 15456516
TI  - Topically applied vitamin C increases the density of dermal papillae in aged
      human skin.
AB  - BACKGROUND: The influence of ageing on the density of the functional entities of
      the papillae containing nutritive capillaries, here in terms as the papillary
      index, and the effect of topically applied vitamin C were investigated by
      confocal laser scanning microscopy (CLSM) in vivo. METHODS: The age dependency of
      the papillary index was determined by CLSM on 3 different age groups.
      Additionally, we determined the effect of a topical cream containing 3% vitamin C
      against the vehicle alone using daily applications for four months on the volar
      forearm of 33 women. RESULTS: There were significant decreases in the papillary
      index showing a clear dependency on age. Topical vitamin C resulted in a
      significant increase of the density of dermal papillae from 4 weeks onward
      compared to its vehicle. Reproducibility was determined in repeated studies.
      CONCLUSIONS: Vitamin C has the potential to enhance the density of dermal
      papillae, perhaps through the mechanism of angiogenesis. Topical vitamin C may
      have therapeutical effects for partial corrections of the regressive structural
      changes associated with the aging process.

PMID- 15456517
TI  - Probiotic prophylaxis in patients with predicted severe acute pancreatitis
      (PROPATRIA): design and rationale of a double-blind, placebo-controlled
      randomised multicenter trial [ISRCTN38327949].
AB  - BACKGROUND: Infectious complications are the major cause of death in acute
      pancreatitis. Small bowel bacterial overgrowth and subsequent bacterial
      translocation are held responsible for the vast majority of these infections.
      Goal of this study is to determine whether selected probiotics are capable of
      preventing infectious complications without the disadvantages of antibiotic
      prophylaxis; antibiotic resistance and fungal overgrowth. METHODS/DESIGN:
      PROPATRIA is a double-blind, placebo-controlled randomised multicenter trial in
      which 200 patients will be randomly allocated to a multispecies probiotic
      preparation (Ecologic 641) or placebo. The study is performed in all 8 Dutch
      University Hospitals and 7 non-University hospitals. The study-product is
      administered twice daily through a nasojejunal tube for 28 days or until
      discharge. Patients eligible for randomisation are adult patients with a first
      onset of predicted severe acute pancreatitis: Imrie criteria 3 or more, CRP 150
      mg/L or more, APACHE II score 8 or more. Exclusion criteria are post-ERCP
      pancreatitis, malignancy, infection/sepsis caused by a second disease, intra
      operative diagnosis of pancreatitis and use of probiotics during the study.
      Administration of the study product is started within 72 hours after onset of
      abdominal pain. The primary endpoint is the total number of infectious
      complications. Secondary endpoints are mortality, necrosectomy, antibiotic
      resistance, hospital stay and adverse events. To demonstrate that probiotic
      prophylaxis reduces the proportion of patients with infectious complications from
      50% to 30%, with alpha 0,05 and power 80%, a total sample size of 200 patients
      was calculated. CONCLUSION: The PROPATRIA study is aimed to show a reduction in
      infectious complications due to early enteral use of multispecies probiotics in
      severe acute pancreatitis.

PMID- 15456518
TI  - The impact of employee level and work stress on mental health and GP service use:
      an analysis of a sample of Australian government employees.
AB  - BACKGROUND: This study sought to identify the extent to which employee level and
      work stressors were associated with mental health problems experienced by
      Australian government employees, and with their use of primary care services.
      METHODS: 806 government employees aged between 40 and 44 years were surveyed as
      part of an epidemiological study conducted in Australia. Data collected from
      participants included sociodemographic attributes, physical health, psychological
      measures and work stressors relating to job control, job demands, job security
      and skills discretion at work. For 88% of these participants, information on
      visits made to general practitioners (GPs) for the six months before and after
      their survey interview was obtained from health insurance records. RESULTS: When
      work stress and personal factors were taken into account, men at more junior
      levels reported better mental health, more positive affect and used fewer GP
      services. Women at middle-management levels obtained less GP care than their more
      senior counterparts. Both men and women who reported higher levels of work stress
      were found to have poorer mental health and well-being. The impact of such
      stressors on GP service use, however, differed for men and women. CONCLUSION:
      Measures of work stress and not employee level affect the mental health and well
      being of government employees. For governments with responsibility for funding
      health care services, reducing work stress experienced by their own employees
      offers potential benefits by improving the health of their workforce and reducing
      outlays for such services.

PMID- 15456519
TI  - Cytotoxicity of psammaplin A from a two-sponge association may correlate with the
      inhibition of DNA replication.
AB  - BACKGROUND: SV40 DNA replication system is a very useful tool to understand the
      mechanism of replication, which is a tightly regulated process. Many
      environmental and cellular factors can induce cell cycle arrest or apoptosis by
      inhibiting DNA replication. In the course of our search for bioactive metabolites
      from the marine sponges, psammaplin A was found to have some anticancer
      properties, the possible mechanism of which was studied. METHODS: Cell viability
      was determined by Cell Counting Kit-8 (CCK-8) to count living RAW264.7 cells by
      combining 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H
      tetrazolium (WST-8) and 1-methoxy-phenazine methosulfate (1-methoxy-PMS). The
      effect of psammaplin A on DNA replication was carried out in SV40 DNA replication
      system in vitro. The activities of topoisomerase I and polymerase alpha-primase
      were measured by the relaxation of superhelical plasmid DNA and the incorporation
      of [3H]dTTP to the template respectively. The ssDNA binding activity of RPA was
      assessed by Gel Mobility Shift Assay (GMSA). RESULTS: We have found that
      psammaplin A delivers significant cytotoxic activity against the RAW264.7 cell
      line. It was also found that psammaplin A could substantially inhibit SV40 DNA
      replication in vitro, in which polymerase alpha-primase is one of its main
      targets. CONCLUSION: Taken together, we suggest that psammaplin A-induced
      cytotoxicity may correlate with its inhibition on DNA replication. Psammaplin A
      has the potential to be developed as an anticancer drug.

PMID- 15456520
TI  - Chemotherapy with cisplatin and vinorelbine for elderly patients with locally
      advanced or metastatic non-small-cell lung cancer (NSCLC).
AB  - BACKGROUND: Although modest improvements in the survival of patients with non
      small cell lung cancer (NSCLC) can be achieved with cisplatin-based chemotherapy
      (CT), its value is disputed in the geriatric setting. In this study, we evaluate
      the feasibility of vinorelbine/cisplatin CT for elderly NSCLC patients. METHODS:
      In this pilot phase I/II trial, all patients received CT with vinorelbine 25
      mg/m2, on day 1 and 8, and cisplatin on day 1, in 28 days-cycles. After
      stratification for age (up to 75 years), younger patients were sequentially
      allocated to moderate cisplatin doses (80 mg/m2 or 90 mg/m2), and older patients
      were allocated to lower cisplatin doses (60 mg/m2 or 70 mg/m2). We recruited
      patients aged over 70 years with newly diagnosed NSCLC, clinical stage III or IV,
      Karnofsky performance status >or= 70%, normal serum creatinine, peripheral
      neuropathy <or= grade 1, and no prior cancer therapy. RESULTS: Analysis was by
      intention to treat. Main toxicities (grade 3-4) was as follows: neutropenia, 20%;
      anemia, 11%; and thrombocytopenia, 2%; alopecia, 55%; fatigue, 11%; and
      peripheral neurotoxicity, 2%. No grade 3-4 emesis or renal toxicity occurred.
      Global median time to progression (TTP) and overall survival (OS) were 27.0 (95%
      CI: 10.1 to 43.7) weeks and 30.1 (95% CI: 24.4 to 35.8) weeks; 1- and 2-year
      survival rates were 36.3% and 13.2%, respectively. Overall response rate was
      50.0% (95% CI: 35.4% to 64.5%), with 1 complete response; no difference on
      response rate was noticed according to cisplatin dose. Median overall survival
      was 30.1 weeks, with 1- and 2-year survival rates of 36.3% and 13.2%,
      respectively. CONCLUSION: Age does not preclude assessment on the role of
      cisplatin-vinorelbine CT for elderly NSCLC patients with good performance status
      and adequate bodily functions.

PMID- 15456521
TI  - Moderate exercise may attenuate some aspects of immunosenescence.
AB  - BACKGROUND: Immunosenescence is related to the deterioration of many immune
      functions, which may be manifested in increased susceptibility to infection,
      cancer, and autoimmunity. Lifestyle factors, such as diet or physical activity,
      may influence the senescence of the immune system. It is widely accepted that
      moderate physical activity may cause beneficial effects for physical and
      psychological health as well as for the immune system activity in aged people.
      METHODS: Thirty elderly women aged 62 to 86 were subjected to a two-years
      authorized physical activity program. Peripheral blood lymphocytes distribution
      and the production of cytokines involved in the immune response development and
      regulation (IL-2, IL-4 and IFN-gamma) were investigated. The same parameters were
      evaluated in two control groups of women: a sedentary group of 12 elderly women
      selected for the second round of the physical activity program and in a group of
      20 sedentary young women. Flow cytometry methods were used for the examination of
      surface markers on peripheral blood lymphocytes and intracellular cytokines
      expression. RESULTS: The distribution of the main lymphocytes subpopulations in
      the peripheral blood of elderly women did not show changes after long-term
      moderate physical training. The percentage of lymphocytes expressing
      intracellular IL-2 was higher in the group of women attending 2-years physical
      activity program than in the control group of elderly sedentary women, and it was
      similar to the value estimated in the group of young sedentary women. There was
      no difference in the intracellular expression of IL-4 and IFN-gamma between the
      active and elderly sedentary women. CONCLUSIONS: Our results suggest that
      moderate, long-term physical activity in elderly women may increase the
      production of IL-2, an important regulator of the immune response. This may help
      ameliorate immunosenescence in these women.

PMID- 15456522
TI  - Is autoinducer-2 a universal signal for interspecies communication: a comparative
      genomic and phylogenetic analysis of the synthesis and signal transduction
      pathways.
AB  - BACKGROUND: Quorum sensing is a process of bacterial cell-to-cell communication
      involving the production and detection of extracellular signaling molecules
      called autoinducers. Recently, it has been proposed that autoinducer-2 (AI-2), a
      furanosyl borate diester derived from the recycling of S-adenosyl-homocysteine
      (SAH) to homocysteine, serves as a universal signal for interspecies
      communication. RESULTS: In this study, 138 completed genomes were examined for
      the genes involved in the synthesis and detection of AI-2. Except for some
      symbionts and parasites, all organisms have a pathway to recycle SAH, either
      using a two-step enzymatic conversion by the Pfs and LuxS enzymes or a one-step
      conversion using SAH-hydrolase (SahH). 51 organisms including most Gamma-, Beta-,
      and Epsilonproteobacteria, and Firmicutes possess the Pfs-LuxS pathway, while
      Archaea, Eukarya, Alphaproteobacteria, Actinobacteria and Cyanobacteria prefer
      the SahH pathway. In all 138 organisms, only the three Vibrio strains had strong,
      bidirectional matches to the periplasmic AI-2 binding protein LuxP and the
      central signal relay protein LuxU. The initial two-component sensor kinase
      protein LuxQ, and the terminal response regulator luxO are found in most
      Proteobacteria, as well as in some Firmicutes, often in several copies.
      CONCLUSIONS: The genomic analysis indicates that the LuxS enzyme required for AI
      2 synthesis is widespread in bacteria, while the periplasmic binding protein LuxP
      is only present in Vibrio strains. Thus, other organisms may either use
      components different from the AI-2 signal transduction system of Vibrio strains
      to sense the signal of AI-2, or they do not have such a quorum sensing system at
      all.

PMID- 15456523
TI  - Huntingtin processing in pathogenesis of Huntington disease.
AB  - Huntingtons disease (HD) is caused by an expansion of the polyglutamine tract in
      the protein named huntingtin. The expansion of polyglutamine tract induces
      selective degeneration of striatal projection neurons and cortical pyramidal
      neurons. The bio-hallmark of HD is the formation of intranuclear inclusions and
      cytoplasmic aggregates in association with other cellular proteins in vulnerable
      neurons. Accumulation of N-terminal mutant huntingtin in HD brains is prominent.
      These pathological features are related to protein misfolding and impairments in
      protein processing and degradation in neurons. This review focused on the role of
      proteases in huntingtin cleavage and degradation and the contribution of altered
      processing of mutant huntingtin to HD pathogenesis.

PMID- 15456524
TI  - Causative and preventive action of calcium in cataracto-genesis.
AB  - Calcium and Ca-dependent enzymes play specific role in the development of human
      cataracts. Entry of Ca2+ into the lens epithelial cells (LEC) is highly regulated
      by quantum of receptors. The Ca2+ level controls homeostasis and growth of entire
      lens. Intracellular overload of Ca2+ in the LEC trigger a series of events such
      as activation of Ca-dependent enzymes, irreversible breakdown of important
      structural proteins and cell death. Proper maintenance of Ca2+ levels by
      regulating activity of Ca-pumps and Ca-channels and inhibition of Ca-dependent
      enzymes can help in prevention of cataract. Induction of cell death in the LEC by
      increase in the intracellular Ca2+ may be utilized for the prevention of
      posterior capsular opacification.

PMID- 15456525
TI  - Comparative acute effects of l-carnitine and dl-carnitine on hepatic catabolism
      of l-alanine and l-glutamine in rats.
AB  - AIM: To compare the acute effects of l-carnitine (LCT) and dl-carnitine (DLC) on
      hepatic catabolism of l-alanine and l-glutamine in rats. METHODS: Livers from 24
      h fasted and fed rats were perfused in situ. The substrates l-alanine (5 mmol/L)
      and l-glutamine (5 mmol/L) were employed. The gluconeogenic and ureogenic
      activity was measured as the difference between the rates of glucose and urea
      released during and before the infusion of l-glutamine or l-alanine. RESULTS: LCT
      (60 micromol/L) but not DLC (60 micromol/L and 120 micromol/L) increased the
      production of glucose and urea from l-glutamine. However, neither LCT (60
      micromol/L and 120 micromol/L) nor DLC (60 micromol/L and 240 micromol/L) showed
      any significant effect on hepatic glucose and urea production from l-alanine.
      CONCLUSION: The results showed a different acute effect of LCT and DLC on the
      activation of hepatic gluconeogenesis and ureagenesis promoted by l-glutamine,
      reinforcing the idea that DLC could not replace LCT.

PMID- 15456526
TI  - In vivo and in vitro chondrotoxicity of ciprofloxacin in juvenile rats.
AB  - AIM: To study the relationship between chondrotoxicity and toxicokinetics of
      ciprofloxacin (CPFX). METHODS: Rats, 4-week old, were treated with CPFX 0, 400,
      800, and 1200 mg/kg ig once daily on seven consecutive days. The knee joint
      cartilage was examined histopathologically. The concentration of CPFX in venous
      blood and knee joint cartilage samples were determined by a microbioassay using
      Escherichia coli 44102. The effects of CPFX on proliferation of chondrocytes and
      secretion of soluble proteoglycans were determined with 3-(4,5-dimethylthiazol-2
      yl)-2,5-diphenyl tetrazolium bromide (MTT) and 1,9-dimethylmethylene blue (DMB)
      assay, respectively. RESULTS: Cartilage was severely lesioned after treatment
      with CPFX 800 or 1200 mg/kg for 7 d, such as matrix swelling and loss of
      chondrocytes. The thickness of cartilage was significantly decreased compared
      with the control group. The maximum serum concentration (Cmax), the area under
      the plasma concentration-time curve (AUC(0-infinity)), and concentration in
      cartilage was 16.3 +/- 2.1 mg/L, 97.2 +/- 12.3 mg x h x L(-1), and 13.4 +/- 2.8
      microg x g(-1) and 21.8 +/- 2.5 mg/L, 143.1 +/- 22.3 mg x h x L(-1), and 20.3 +/-
      3.5 microg x g(-1) after oral administration of CPFX 800 or 1200 mg/kg on d 1,
      respectively. The data on d 6 were similar with that on d 1. CPFX inhibited
      proliferation of chondrocytes and the secretion of soluble proteoglycans.
      CONCLUSION: CPFX concentrations in serum and cartilage could provide a better
      basis for risk assessment.

PMID- 15456527
TI  - Effects of beta-aescin on apoptosis induced by transient focal cerebral ischemia
      in rats.
AB  - AIM: To investigate the effects of beta-aescin on apoptosis induced by transient
      focal brain ischemia in rats. METHODS: Rats were pretreated with beta-aescin for
      7 d and then subjected to brain ischemia/reperfusion (I/R) injury induced by a
      middle cerebral artery occlusion. After 2 h ischemia and 24 h reperfusion,
      Hematoxylin-Eosin (HE) staining, in situ end-labeling of nuclear DNA
      fragmentation (TUNEL) were employed to determine the level of apoptosis. The
      expressions of caspase-3 and Bcl-2 in the cortex were determined by
      immunohistochemistry and Western blot. The release of cytochrome c was analyzed
      by Western blot. RESULTS: The increased numbers of HE- and TUNEL-positive
      staining cells were significantly observed at 24 h after reperfusion. The
      immunoreactivity was inhibited by beta-aescin (30, 60 mg/kg) (P<0.01 or P<0.05 vs
      vehicle-treated). After cerebral I/R, cytochrome c was released into the cytosol
      and caspase-3 was activated, whereas Bcl-2 expression was inhibited. beta-Aescin
      (30, 60 mg/kg) markedly inhibited the expression of caspase-3 and the release of
      cytochrome c, and up-regulated the expression of Bcl-2 (P<0.05, P<0.01 vs vehicle
      treated). CONCLUSION: beta-Aescin could potently inhibit caspase-3 activation and
      the release of cytochrome c, increasing the expression of Bcl-2 after cerebral
      I/R in rats. These findings on the inhibitory effects of beta-aescin on brain
      ischemic injury-induced apoptosis might have important theoretical basis for the
      treatment on ischemic cerebrovascular diseases.

PMID- 15456528
TI  - Protective effect of tubuloside B on TNFalpha-induced apoptosis in neuronal
      cells.
AB  - AIM: To investigate the neuroprotective effect of tubuloside B, one of the
      phenylethanoids isolated from the stems of Cistanche salsa, on tumor necrosis
      factor-alpha (TNFalpha)-induced apoptosis in SH-SY5Y neuronal cells. METHODS:
      Cell viability was analyzed using MTT assay. Apoptotic cells were detected using
      Hoechst33342 staining, and confirmed by DNA fragmentation and flow cytometric
      analysis. The activity of caspase-3 was measured with special assay kit. The
      concentration of free intracellular calcium was determined with the probe Indo-1
      by spectrometer. The level of intracellular reactive oxygen species and the
      potential of mitochondrial membrane were determined by laser scanning confocal
      microscopy (LSCM) combined with fluorescence probe H2DCFDA or JC-1 respectively.
      RESULTS: SH-SY5Y cells treated with TNFalpha 100 microg/L for 36 h showed typical
      morphological changes of apoptosis. DNA ladder could be observed by agarose gel
      electrophoresis. The highest percentage of apoptotic cells accumulated to 37.5 %.
      Following 36 h treatment with TNFalpha, accumulation of intracellular ROS and
      [Ca2+]i and decrease in mitochondrial membrane potential were observed, and
      caspase-3 activity increased by about five-fold compared with controls. However,
      pretreatment with tubuloside B (1, 10, or 100 mg/L) for 2 h attenuated the
      TNFalpha-mediated apoptosis. The antiapoptotic action of tubuloside B was
      partially dependent on an anti-oxidative stress effects, maintain of mitochondria
      function, decrease of concentration of free intracellular calcium and inhibition
      of caspase-3 activity. CONCLUSION: Tubuloside B has the neuroprotective capacity
      to antagonize TNFalpha-induced apoptosis in SH-SY5Y cells and may be useful in
      treating some neurodegenerative diseases.

PMID- 15456529
TI  - Effects of morphine dependence and withdrawal on levels of neurosteroids in rat
      brain.
AB  - AIM: To investigate the effects of morphine dependence and withdrawal on the
      concentrations of neurosteroids in rat brain. METHODS: A method of simultaneous
      quantification of neurosteroids by gas chromatography-mass spectrometry (GC-MS)
      had been established. RESULTS: The chronic morphine administration (ip) resulted
      in a marked decrease in the brain concentrations of pregnenolone (PREG),
      progesterone (PROG), and pregenenolone sulfate (PREGS) in rats killed 6 h after
      the last treatment. In contrast, there were no significant effects of morphine
      dependence on the brain concentrations of allopregnanolone (AP),
      dihydroepiandrosterone (DHEA), and dihydroepiandrosterone sulfate (DHEAS).
      Naloxone-induced withdrawal produced a significant increase in the concentrations
      of PREG, PROG, AP, DHEA, PREGS, and DHEAS as compared with the control group.
      CONCLUSION: Morphine dependence and withdrawal affected the concentrations of
      neurosteroids in rat brain, which suggests that endogenous neurosteroids in brain
      might be related to the development of morphine dependence and withdrawal.

PMID- 15456530
TI  - Production of neutralizing monoclonal antibody against human vascular endothelial
      growth factor receptor II.
AB  - AIM: To prepare neutralizing monoclonal antibody (mAb) against extracellular
      immunoglobulin (Ig)-like domain III of vascular endothelial growth factor
      receptor KDR and study its biological activity. METHODS: Soluble KDR Ig domain
      III (KDR-III) fusion protein was expressed in E Coli and purified from the
      bacterial periplasmic extracts via an affinity chromatography. Monoclonal
      antibodies against KDR-III were prepared by hybridoma technique. ELISA and FACS
      analysis were used to identify its specificity. Immunoprecipitation and [3H]
      thymidine incorporation assay were also used to detect the activity of anti-KDR
      mAb blocking the phosphorylation of KDR tyrosine kinase receptor and the
      influence on vascular endothelial growth factor-induced mitogenesis of human
      endothelial cells. RESULTS: A monoclonal antibody, Ycom1D3 (IgG1), was generated
      from a mouse immunized with the recombinant KDR-III protein. Ycom1D3 bound
      specifically to both the soluble KDR-III and the cell-surface expressed KDR.
      Ycom1D3 effectively blocked VEGF/KDR interaction and inhibited VEGF-stimulated
      KDR activation in human endothelial cells. Furthermore, the antibody efficiently
      neutralized VEGF-induced mitogenesis of human endothelial cells. CONCLUSION: Our
      results suggest that the anti-KDR mAb, Ycom1D3, has potential applications in the
      treatment of cancer and other diseases where pathological angiogenesis is
      involved.

PMID- 15456531
TI  - Acidosis-induced p38 MAPK activation and its implication in regulation of cardiac
      contractility.
AB  - AIM: To determine the possible role of pH in mediating activation of p38 mitogen
      activated protein kinase (MAPK) and the consequent function of activated p38 MAPK
      in regulating cardiac contractility. METHODS: Adult rat cardiomyocytes were
      isolated and cultured. Low pH media was used to induce intracellular acidosis and
      contraction of single cardiomyocyte was measured. RESULTS: Phosphorylation of p38
      MAPK was increased during ischemia, and pHi was decreased. Intracellular acidosis
      activated p38 MAPK to a similar level as ischemia. Inhibition of p38 MAPK
      activation by SB203580, a specific inhibitor of p38 MAPK, reversed acidosis
      mediated reduction of myocyte contractility. CONCLUSION: In adult rat
      cardiomyocytes, intracellular acidification activated p38 MAPK and decreased
      cardiac contractility. Pretreatment of cardiomyocytes with SB203580 completely
      blocked p38 MAPK activation and partially reversed acidosis-mediated decline of
      cardiac contractility.

PMID- 15456532
TI  - Inhibitory effect of extracts of Ginkgo biloba leaves on VEGF-induced
      hyperpermeability of bovine coronary endothelial cells in vitro.
AB  - AIM: To study whether extract of Ginkgo biloba (EGb) can protect against
      atherosclerosis. METHODS: Confluent monolayers of bovine coronary endothelial
      cells (BCECs), bovine coronary smooth muscle cells (BCSMCs), and cocultures of
      the two were incubated with medium containing VEGF and/or EGb, and flux of 125I
      labeled oxidized low density lipoprotein (ox-LDL) across the monolayers was
      measured. RESULTS: Incubation with VEGF significantly increased the permeability
      of BCEC monolayers to 125I-ox-LDL in a time- and concentration-dependent manner,
      but had no effect on permeability of BCSMCs or endothelial cells-smooth muscle
      cells cocultures. EGb significantly inhibited the VEGF-induced hyperpermeability
      of BCECs. CONCLUSION: VEGF was important in the formation and development of
      atherosclerosis. The inhibition of VEGF-induced permeability by EGb suggests that
      extracts of Ginkgo biloba leaves may have important clinical applications in the
      treatment of cardiovascular diseases.

PMID- 15456533
TI  - A novel PPAR alpha/gamma dual agonist inhibits cell growth and induces apoptosis
      in human glioblastoma T98G cells.
AB  - AIM: To examine the effect of a novel peroxisome proliferator-activated receptor
      (PPAR) alpha/gamma dual agonist TZD18 on cell proliferation and apoptosis in
      human glioblastoma T98G cells and its possible mechanism. METHODS: RT-PCR, MTT,
      TUNEL, Flow cytometry, and Western blot analysis were employed. RESULTS: TZD18
      inhibited the growth of T98G cells in a concentration-dependent manner, which was
      associated with a G1 to S cell cycle arrest. Besides, significant apoptosis was
      induced after treatment with a non-toxic dose of TZD18. During the process, the
      expression of Bcl-2 protein was down-regulated, while that of Bax and p27kip
      proteins was up-regulated, and the activity of caspase-3 was elevated. However,
      this effect appeared to be PPARalpha and PPARgamma independent since their
      antagonists could not reverse this effect. CONCLUSIONS: TZD18, a novel
      PPARalpha/gamma dual agonist, inhibited cell growth and induce apoptosis in human
      glioblastoma T98G cells in vitro, indicating a therapeutic potential for TZD18 in
      the treatment of glioblastoma.

PMID- 15456534
TI  - Different roles of PKC and PKA in effect of interferon-gamma on proliferation and
      collagen synthesis of fibroblasts.
AB  - AIM: To study the signal roles of protein kinase C (PKC) and protein kinase A
      (PKA) in the influence of interferon-gamma (IFN-gamma) on proliferation and
      collagen synthesis of fibroblasts derived from hypertrophic scar (HS-FB) and
      normal skin (NS-FB). METHODS: HS-FB and NS-FB were cultured and passaged in
      Dulbecco modified Eagles medium (DMEM). Activity of PKC and PKA were assayed by
      transferring phosphorus (32P) into substrate after treatment with IFN-gamma 1000
      kU/L at 10, 30, 60, and 120 min. Cell proliferation was determined with MTT
      assay. The collagen synthesis was measured with [3H]proline incorporation and
      Type III pre-collagen was determined with radioimmunoassay. RESULTS: After
      exposure to IFN-gamma 1000 kU/L for 30 min, PKC activity of HS-FB and NS-FB
      increased from 2.57 +/- 0.14 and 2.13 +/- 0.12 nmol x min(-1) x g(-1) of control
      to 3.75 +/- 0.19 and 3.36 +/- 0.16 nmol x min(-1) x g(-1), respectively (P <
      0.05). After exposure to IFN-gamma 1000 kU/L for 60 and 120 min, PKA activities
      of HS-FB increased gradually from 0.82 +/- 0.04 nmol x min(-1) x g(-1) of control
      to 1.03 +/- 0.05 and 1.23 +/- 0.06 nmol x min(-1) x g(-1), respectively (P<0.05).
      The PKA activities of NS-FB also increased from 0.52 +/- 0.03 nmol x min(-1) x g(
      1) of control to 0.68 +/- 0.03 and 0.89 +/- 0.05 nmol x min(-1) x g(-1),
      respectively (P<0.05). The proliferation and collagen synthesis were enhanced by
      PKC activator (containing phosphatidylserine, diacylglycerol and Ca2+) and PKA
      inhibitor [H(7)250 micromol/L, 1-(5-isoquinolinylsulfonyl)-2-methyl piperazine],
      and inhibited by PKC inhibitor (GF109 250 micromol/L) and PKA activator (cAMP 25
      micromol/L) (P<0.01). GF109 abrogated increased proliferation and collagen
      synthesis by IFN-gamma but it did not affect the inhibitory effects of IFN-gamma.
      At 120 min H7 reversed the inhibitory functions of IFN-gamma. CONCLUSION: IFN
      gamma transiently increased proliferation and collagen synthesis of HS-FB and NS
      FB by activation of PKC and subsequently inhibited proliferation and collagen
      synthesis by activation of PKA.

PMID- 15456535
TI  - Effects of aspirin on metastasis-associated gene expression detected by cDNA
      microarray.
AB  - AIM: To investigate the effect of aspirin on the metastasis-associated gene
      expression in 3AO ovarian cancer cells. METHODS: 3AO cells were treated with
      aspirin at the concentration of 1.2 mmol/L for 16 and 48 h, respectively. The
      total RNA was extracted with Trizol reagents and reverse transcribed with
      Superscript II and hybridized with cDNA microarray (containing oncogenes, tumor
      suppressor genes, signal transduction pathway molecules, adhesive molecules,
      growth factors and ESTs) fabricated in our lab. After normalization, the ratio of
      gene expression of aspirin treated to untreated 3AO cells being either 2 fold up
      higher or 0.5 fold down (lower) were defined as differential expression. Semi
      quantitative RT-PCR was used to validate the microarray results. RESULTS: Among
      the 447 metastasis-associated genes, 4 genes were up-regulated and 14 genes were
      down-regulated in 3AO cells treated with aspirin for 16 h compared with untreated
      cells. While 24 genes were up-regulated and 10 genes were down-regulated in cells
      treated with aspirin for 48 h. Several up or down-regulated gene expression
      changes continued from 16 h to 48 h. CONCLUSION: Aspirin might exert its anti
      metastasis effects on ovarian cancer by affecting metastasis-associated gene
      expression.

PMID- 15456536
TI  - Effects of ulinastatin on renal ischemia-reperfusion injury in rats.
AB  - AIM: To investigate the effect and possible mechanism of ulinastatin on renal
      ischemia-reperfusion injury in rats. METHODS: Male Sprague-Dawley rats were
      subjected to 45-min bilateral renal ischemia, treated with intravenously 12,500 U
      ulinastatin at 30 min prior to ischemia and at the beginning of reperfusion,
      compared with a nontreated group without ulinastatin and a sham-operation group
      without bilateral renal ischemia. After 0 h, 2 h, 6 h, 12 h, and 24 h of
      reperfusion, serum creatinine and blood urea nitrogen were measured for the
      assessment of renal function, renal sections were used for histologic grading of
      renal injury, for immunohistochemical localization of Bcl-2 and heat shock
      protein 70. Renal ultrastructure was observed through a transmission electron
      microscope. RESULTS: Ulinastatin significantly reduced the increase in blood urea
      nitrogen and creatinine produced by renal ischemia-reperfusion, suggesting an
      improvement in renal function. Ulinastatin reduced the histologic evidence of
      renal damage associated with ischemia-reperfusion and accompanied with an up
      regulation in the expression of Bcl-2 protein, but it had no significant effect
      on the expression of HSP 70. Ulinastatin also significantly reduced kidney
      ultrastructure damage caused by renal ischemia-reperfusion. CONCLUSION: The
      protease inhibitor, ulinastatin, reduced the renal dysfunction and injury
      associated with ischemia-reperfusion of the kidney. The protective effect of
      ulinastatin might be associated with the up-regulation of Bcl-2 expression and
      the effect on membrane fragility.

PMID- 15456537
TI  - Montelukast modulates lung CysLT(1) receptor expression and eosinophilic
      inflammation in asthmatic mice.
AB  - AIM: To determine the expressions of cysteinyl leukotriene receptors, CysLT1 and
      CysLT2, in airway eosinophilic inflammation of OVA-induced asthmatic mice and the
      modulation by montelukast, a CysLT1 receptor antagonist. METHODS: Asthma model
      was induced by chronic exposure to ovalbumin (OVA) in C57BL/6 mice. The
      eosinophils in bronchoalveolar lavage (BAL) fluid and lung tissues were counted,
      IL-5 level in BAL fluid was measured, and CysLT1 and CysLT2 receptor mRNA
      expressions were detected by semi-quantitative RT-PCR. RESULTS: Montelukast (6
      mg/kg, once per day for 20 d) significantly suppressed the increased eosinophils
      in BAL fluid and lung tissue, and increased IL-5 level in BAL fluid in OVA
      challenged mice. OVA challenge increased CysLT1 but decreased CysLT2 receptor
      mRNA expression. Montelukast inhibited the increased CysLT1 but not the reduced
      CysLT2 expression after OVA challenge. CONCLUSION: CysLT receptors are modulated
      immunologically, and montelukast inhibits up-regulation of CysLT1 receptor and
      airway eosinophilic inflammation in asthmatic mice.

PMID- 15456538
TI  - Effect of lipopolysaccharide on expression and characterization of
      cholecystokinin receptors in rat pulmonary interstitial macrophages.
AB  - AIM: To investigate the effect of lipopolysaccharide (LPS) on the expression and
      the binding characteristics of cholecystokinin receptors (CCK-R) in rat pulmonary
      interstitial macrophages (PIMs). METHODS: The PIMs isolated from rat lung tissues
      were purified by the collagenase digestion method combined with alveolar lavage
      and pulmonary vessel perfusion. The expression of CCK-R mRNA was detected by RT
      PCR and Southern blot analysis and the binding experiments were performed by
      radioligand binding assay (RBA). RESULTS: CCK-A receptor (CCK-AR) and CCK-B
      receptor (CCK-BR) mRNA were detected in rat PIMs and their RT-PCR amplified
      products had a size of approximately 1.37 kb and 480 bp, respectively. The
      relative expression of CCK-BR mRNA was higher than that of CCK-AR mRNA after
      incubation with LPS for 0.5, 2, and 6 h. The expression of CCK-R mRNA could be
      upregulated obviously by LPS. Southern blot analysis of RT-PCR amplified CCK-AR
      and CCK-BR mRNA products using [gamma-32P]ATP 5'-end-labelled probe showed
      specific hybridization bands. The specific binding of [3H]CCK-8S to rat PIM
      membranes was detected in the rats administered with LPS for 48 h, but not in
      normal rats. Scatchard analysis of the saturation curves suggested the presence
      of CCK-R with a high affinity (Kd = 0.68 +/- 0.28 nmol/L) and a low binding
      capacity (Bmax = 32.5 +/- 2.7 fmol/g protein) in rat PIMs. The specific binding
      of [3H]CCK-8S to rat PIM membranes was inhibited by unlabelled CCK-8S (IC50 = 2.3
      +/- 0.8 nmol/L), CCK-AR specific antagonist CR1409 (IC50 = 0.19 +/- 0.06
      micromol/L) and CCK-BR specific antagonist CR2945 (IC50 = 3.2 +/- 0.1 nmol/L).
      CONCLUSION: Two types of functional CCK-AR and CCK-BR existed in rat PIMs and
      their expression could be upregulated by LPS.

PMID- 15456539
TI  - Effect of catecholamines on IL-2 production and NK cytotoxicity of rats in vitro.
AB  - AIM: To explore effects of exogenous and endogenous catecholamines on function of
      lymphocytes and primary mechanisms mediating the effects. METHODS: Splenocytes of
      rats were exposed to norepinephrine (NE), alpha- or beta-adrenoceptor antagonists
      plus NE, or alpha-methyl-p-tyrosine (alpha-MT), and then concanavalin A (Con A)
      induced interleukin-2 (IL-2) production and natural killer (NK) cell cytotoxicity
      were determined by MTT assay and LDH assay, respectively. RESULTS: Optical
      density (OD) values of NE-treated groups, which reflected IL-2 production, were
      0.63, 0.61, and 0.60, respectively for 10(-10), 10(-9), and 10(-8) mol/L NE. They
      were all significantly reduced in comparison with control value of 0.68 (P<0.01).
      The effect of NE was blocked by either phentolamine (an alpha-adrenoceptor
      antagonist) or propanolol (a beta-adrenoceptor antagonist). OD values of alpha
      MT, an inhibitor of tyrosine hydroxylase, at doses of 10(-10), 10(-9), and 10(-8)
      mol/L respectively were 0.71, 0.71, and 0.69, which were all notably higher than
      that of control (0.65, P<0.01). NK cytotoxicity was markedly attenuated by both
      NE and alpha-MT at the three doses mentioned above (17.69 %, 17.06 %, and 16.89 %
      versus 25.18 % for NE; 18.85 %, 18.44 %, and 17.04 % versus 23.22 % for alpha-MT;
      all P<0.01). The suppression of NK cytotoxicity by NE was prevented by
      propranolol but not by phentolamine. CONCLUSION: Exogenous NE exerts a
      suppressive action in modulating functions of T and NK cells, with the former via
      both alpha- and beta-adrenoceptor mediated mechanisms and the later mainly
      through beta-adrenoceptors. Endogenous catecholamines synthesized by lymphocytes
      have also an autoregulatory effect on the lymphocytes themselves.

PMID- 15456540
TI  - Interaction between M-CSF and IL-10 on productions of IL-12 and IL-18 and
      expressions of CD14, CD23, and CD64 by human monocytes.
AB  - AIM: To Study the interaction of macrophage colony-stimulating factor (M-CSF) and
      interleukin-10 (IL-10) in productions of IL-12 and IL-18 and expressions of CD14,
      CD23, and CD64 by human monocytes. METHODS: Purified adherent human monocytes
      were cultured with M-CSF or IL-10 alone, or with M-CSF+IL-10 and 2-3d later, the
      culture supernatants and cells were separated and collected. IL-12P40 and IL-18
      levels in the supernatants were determined by ELISA and the percentages of CD14,
      CD23, and CD64 positive cells were examined by flow cytometry. RESULTS: (1) IL-10
      decreased M-CSF-induced IL-18 levels, while M-CSF further reduced IL-12P40 level
      in the culture supernatants of IL-10-treated monocytes; (2) IL-10 alone had no
      effect on the percentage of CD14-positive cells, but further increased the
      percentage of CD14-positive cells induced by M-CSF; M-CSF alone had no effect on
      the percentage of CD64-positive cells, but further increased the percentage of
      CD64-positive cells induced by IL-10; (3) IL-10 decreased the percentage of CD23
      positive cells induced by M-CSF. CONCLUSION: Between M-CSF and IL-10, there were
      antagonistic effects on inducing IL-18 and CD23 expressions by monocytes; there
      were also synergistic effects on inhibiting IL-12P40 production and inducing CD14
      and CD64 expressions by monocytes.

PMID- 15456541
TI  - Dilazep and dipyridamole inhibit tissue factor expression on monocytes induced by
      IgG from patients with antiphospholipid syndrome.
AB  - AIM: To investigate whether antiplatelet agents, dilazep and dipyridamole,
      inhibit tissue factor (TF) expression on monocytes induced by IgG from patients
      with antiphospholipid syndrome (APS). METHODS: Freshly isolated peripheral blood
      monocytes were allowed to adhere on plastic and then cultured in media containing
      patient or control antibodies and/or other agonists with or without dilazep or
      dipyridamole. The TF activity on monocytes was investigated by measuring factor
      VIIa-dependent generation of factor Xa, using a chromogenic substrate and the TF
      mRNA expression was examined by real-time PCR (TaqMan PCR). RESULTS: The TF
      activity on monocytes induced by APS IgG (250 mg/L) was inhibited by dilazep
      (0.15-150 micromol/L) and dipyridamole (0.2-200 micromol/L) in a dose-dependent
      fashion. But, the TF mRNA expression induced by APS IgG was not inhibited.
      Theophylline (500 micromol/L), an adenosine receptor antagonist, could counteract
      the inhibitory effect of dilazep and dipyridamole on TF activity. CONCLUSION:
      Antiplatelet agents, dilazep and dipyridamole, block APS IgG-induced monocytes TF
      expression at a post-transcriptional level, partly by adenosine receptor pathway.
      Pharmacological agents that block monocytes TF activity, such as dilazep and
      dipyridamole, are a novel therapeutic approach in APS.

PMID- 15456542
TI  - Je-chun-jun induced apoptosis of human cervical carcinoma HeLa cells.
AB  - AIM: To study the mechanism of je-chun-jun (JCJ)-inducing the apoptosis of the
      human cervical carcinoma, HeLa cells. METHODS: The cell viability was assessed
      using MTT assay. The optical density was measured at 570 nm. The caspase activity
      was measured using 50 mmol/L of fluorogenic substrate, AC-DEVD-AMC (caspase-3),
      AC-VEID-AMC (caspase-8) or AC-LEHD-AFC (caspase-9). To confirm the expression of
      proteins, Western blotting was performed. To detect the characteristic of
      apoptosis chromatin condensation, HeLa cells were stained with Hoechst 33258 in
      the presence of JCJ. For the cell cycle analysis, HeLa cells were incubated with
      Propidium iodide (PI) solution. Fluorescence intensity of cell cycle was measured
      using flow cytometry system. RESULTS: The loss of viability occurred following
      the exposure of 10 g/L JCJ. Cells treated with 10 g/L JCJ for 3 d exhibited the
      apoptotic morphology (brightly blue-fluorescent condensed nuclei by Hoechst 33258
      staining) and the reduction of cell volume. Cells incubated with JCJ for 48 h
      were arrested at the G1 phase of cell cycle and their G1 checkpoint related gene
      products such as cyclin D1 were transiently decreased. We showed that JCJ induced
      the p38 MAPK activation in HeLa cells. The p38 MAPK inhibitor, SB203580 protected
      Hela cells from the JCJ-induced death as well as intervened the JCJ-induced
      accumulation of cells at the G1 phase. In contrast, MEK1 (-ERK upstream)
      inhibitor, PD98059 had no effect on HeLa cells. CONCLUSION: JCJ induced cell
      cycle arrest and apoptosis of HeLa cells through p38 MAPK pathway.

PMID- 15456543
TI  - Octreotide inhibits proliferation and induces apoptosis of hepatocellular
      carcinoma cells.
AB  - AIM: To study the effect of octreotide on cell proliferation and apoptosis in
      different hepatocellular carcinoma (HCC) cells and hepatocytes. METHODS: The
      proliferation of HCC cells (HepG2, SMMC-7721) and hepatocytes (L-02) was
      determined by MTT assay. Apoptosis was detected either by fluorescent staining,
      transmission electron microscopy or flow cytometry. The content of AFP in the
      supernatant of cultured HCC cells was determined by electrochemiluminescence
      immunoassay. The expression of SSTR subtypes was identified by RT-PCR. RESULTS:
      The proliferation of HCC cells and L-02 cells was inhibited significantly by
      octreotide (0.25, 0.5, 1.0, 2.0 and 4.0 mg/L). However, the apoptosis of HCC
      cells markedly increased in a concentration-dependent manner. Both the apoptosis
      index and the percentage of apoptotic cells in L-02 cells were significantly
      lower than those of HepG2 and SMMC-7721 cells. The content of AFP in the
      supernatant of cultured HepG2 cells treated with octreotide was also
      statistically reduced. Furthermore, SSTR2 and SSTR4 were positive in both the
      hepatocellular carcinoma cells and in the L-02 cells. SSTR3 was only expressed in
      the two heptatocellular carcinoma cells, and SSTR5 was found in the SMMC-7721
      cells. No SSTR1 was detected either in HCC cells or L-02 cells. CONCLUSIONS:
      Apoptosis induction is a major mechanism of octreotide inhibition on
      hepatocellular cells. SSTR3 is expressed in the HCC cells, but not in the L-02
      cells, which suggests a molecular basis for the HCC-selective effects of
      octreotide.

PMID- 15456544
TI  - Hands-on guide to writing case reports for the JCPSP.

PMID- 15456545
TI  - Efficacy of camphorated paramonochlorophenol to a mixture of honey and mustard
      oil as a root canal medicament.
AB  - OBJECTIVE: To compare the efficacy of camphorated paramonochlorophenol to a
      mixture of honey and mustard oil as a root canal medicament. DESIGN: An in vitro
      comparative study. PLACE AND DURATION OF STUDY: This study was carried out in
      collaboration with microbiology department of Armed Forces Institute of
      Pathology, Rawalpindi and was conducted from Aug-2001 to Nov-2001. MATERIALS AND
      METHODS: A sample of 90 infected root canal contents of decayed teeth was
      collected from Operative Dentistry Department of Armed Forces Institute of
      Dentistry, Rawalpindi. Each sample was inoculated aerobically as well as an
      aerobically. Organisms were identified and isolates were preserved and
      refrigerated for experiments. Medicaments were procured and prepared in
      comparable dilutions. Minimum inhibitory concentration of both medicaments was
      compared by susceptibility testing against already preserved isolates. RESULTS:
      The tested mixture (honey and mustard oil equal v/v ) demonstrated antibacterial
      activity against all isolates at concentration of 12.5%(mean of effective
      conc.17.11%) while that of camphorated paramonochlorophenol was comparably at
      higher concentration 3.1%(mean of effective conc. 3.35%). However the mixture
      revealed better results than that of individual agents, which was 12.5% to 25%
      respectively. CONCLUSION: Mixture (honey and mustard oil) was effective, viable
      alternate endodontic medicament.

PMID- 15456546
TI  - Placement and replacement of dental restorations.
AB  - OBJECTIVE: To determine the types of various dental restorative materials used,
      and the reasons for the placement and replacement of dental restorations in 10
      randomly selected polyclinics in Riyadh, Saudi Arabia. DESIGN: A cross-sectional
      descriptive study. PLACE AND DURATION OF STUDY: Ten selected polyclinics in
      Riyadh metropolitan area, Saudi Arabia during a period of two weeks in January
      2003. PATIENTS AND METHODS: Information was collected by using a specially
      designed form that was distributed to one dentist in each selected polyclinic.
      The dentists were asked to record specific details for all restorations placed in
      adult patients. Chi-square tests were used to analyze the data. RESULTS: Data
      were collected for 326 restorations. Amalgam (52.5%) was the most commonly used
      restorative material followed by resin composite (31.3%) and temporary
      restorations (14.4%), with a minimal use of glass ionomer cement (1.8%, p<0.001).
      Most of the restorations (69.9%) were initial placements, while 30.1% were
      replacement restorations, (p<0.05). Caries was the major reason for the initial
      placement (92.1%), and for the subsequent replacement (96.9%) of restorations.
      CONCLUSION: Amalgam and resin composite were the most commonly used restorative
      materials. Caries was the major reason for the initial restoration placements and
      subsequent replacements.

PMID- 15456547
TI  - Comparative efficacy of psoralen - UVA photochemotherapy versus narrow band UVB
      phototherapy in the treatment of psoriasis.
AB  - OBJECTIVE: To compare the clinical improvement in psoriasis with psoralen - UVA
      photochemotherapy versus narrow band UVB phototherapy alone. DESIGN: An
      interventional quasi- experimental study. PLACE AND DURATION OF STUDY:
      Dermatology Department, Nishtar Hospital, Multan, from May 2002 to June 2003.
      PATIENTS AND METHODS: Forty patients with chronic plaque type psoriasis were
      included in the study. These were divided into two equal groups each having 20
      patients. PUVA or UVB therapy was given thrice weekly. Clinical improvement in
      lesions was observed by decrease in the severity of erythema, scaling and plaque
      elevation. RESULTS: Clearance of psoriasis was achieved in significantly greater
      proportion of patients treated with PUVA (85%) than with UVB phototherapy (60%)
      (p=0.03814). Significantly fewer number of exposures were required for clearance
      with PUVA (median number of treatments=17) as compared to UVB (median number of
      treatments=25.5) (p=0.0002). Median cumulative dose for PUVA was 69.1 J/cm2 and
      for UVB was 34.15 J/cm2, respectively (p<0.0001). CONCLUSION: When given thrice
      weekly, PUVA was more effective treatment for psoriasis than narrow band UVB
      phototherapy.

PMID- 15456548
TI  - Role of MRI in differentiating various causes of non-traumatic paraparesis and
      tetraparesis.
AB  - OBJECTIVE: To assess the frequency of various causes of non-traumatic paraparesis
      and tetraparesis in adults based only on the findings of magnetic resonance
      imaging (MRI). DESIGN: Non-interventional descriptive study carried out from May
      2001 to October 2002 at Radiology Department, CMH, Rawalpindi. PATIENTS AND
      METHODS: A total of 100 adult patients who presented with non-traumatic
      paraparesis or tetraparesis, were studied. MRI spine of all the patients and MRI
      brain of selected patients, was carried out. Based on MRI findings alone causes
      of non-traumatic paraparesis and tetraparesis were categorized. RESULTS:
      Paraparesis was more frequent than tetraparesis. Cord compression was found in
      72% cases. Neoplastic compression, infective spondylitis and non-compressive
      myelopathies were the main causes of paraparesis while spondylotic myelopathy was
      the main cause of tetraparesis. CONCLUSION: Based upon MRI findings causes of non
      traumatic paraparesis or tetraparesis can be subcategorized into spondylotic,
      infective or neoplastic cord compression and non-compressive myelopathies.
      Further subcategorization of neoplastic lesions according to their compartment of
      origin can also be done.

PMID- 15456549
TI  - Ultrasound in the diagnosis and management of intrauterine growth retardation.
AB  - OBJECTIVE: To evaluate the value of ultrasound in the diagnosis and management
      strategies of intrauterine growth retardation. DESIGN: A descriptive study. PLACE
      AND DURATION OF STUDY: Radiology Department, Aga Khan University Hospital,
      Karachi, from April 1998 to August 1999. PATIENTS AND METHODS: The study
      population comprised of 206 subjects evaluated for suspected intrauterine growth
      retardation. Grey scale as well as Doppler ultrasound findings were evaluated and
      compared against post-natal outcome. RESULTS: One hundred and eight out of 206
      subjects showed positive imaging results with 40 false positive and 20 false
      negative subjects. The sensitivity, specificity, positive predictive and negative
      predictive values were 77.8%, 66.1%, 55.6%, and 45.1% respectively. Forty
      subjects showed false positive results on imaging (low biophysical profile score
      and Grey scale biometry discrepancy) while 20 of the subjects showed false
      negative results (normal on US imaging) when compared with postnatal neonatal
      body weight criteria. Twenty-two subjects had oligohydramnios with amniotic fluid
      index below 5 percentile for their respective gestational ages (20%) out of 108.
      CONCLUSION: Obstetric and Doppler ultrasound is an accurate method for diagnosis
      and management of fetal growth retardation.

PMID- 15456550
TI  - Magnesium sulphate as an anticonvulsant in the management of eclampsia.
AB  - OBJECTIVE: To evaluate the use of magnesium sulphate (MgSO4) as an anticonvulsant
      in the management of eclamptic patients. DESIGN: A cross-sectional study. PLACE
      AND DURATION OF STUDY: This study was carried out at Sobhraj Maternity Hospital
      over a period of 2 years from January 1999 to December 2000. PATIENTS AND
      METHODS: Out of a total of 6050 pregnant women, 31 patients had eclampsia and
      were managed according to the set protocol. MgSO4 was given to eclamptic patients
      according to protocol who had no contraindication to this agent. Recurrence of
      convulsion, side effects of magnesium sulphate, maternal and fetal outcome were
      noted. RESULTS: Over two years' study period, out of 6050 patients, 31 were
      admitted with eclampsia (0.51%). There was no maternal death. Out of 31 eclamptic
      patients only 5 patients were booked. Twenty-two patients (70.9%) were
      primigravida and 9 (29%) were multigravida. Seventeen (54%) were less than 20
      years of age, 22 (79.9%) patients were admitted with antepartum and 6 (19.35%)
      had postpartum eclampsia. Magnesium sulphate was effective in 29 (93.54%)
      patients. Fifteen patients delivered by caesarean (C) section and 16 delivered
      vaginally. Twenty-nine (93.5%) babies were born alive. Two patients had recurrent
      convulsion i.e. 6.4%. Only one patient had respiratory depression after the use
      of magnesium sulphate. CONCLUSION: Eclampsia was well-controlled by the use of
      MgSO4. There were only 2 patients who had recurrence of convulsion. Convulsions
      were controlled in 29 (93.54%) patients despite lack of monitoring facilities of
      serum magnesium level.

PMID- 15456551
TI  - Spaghetti wrist: management and outcome.
AB  - OBJECTIVE: To determine the outcome of emergency management of the spaghetti
      wrist. DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Department of
      General Surgery, Sir Ganga Ram Hospital Lahore, Pakistan, from January 2000 to
      December 2003. PATIENTS AND METHODS: During this period, all patients of more
      than 12 years, with sharp clean cut volar forearm lacerations (spaghetti wrist)
      of <6 hours were included, with a follow-up of one year, clinically and with
      nerve conduction studies, where appropriate. Sensory and motor recovery was
      evaluated according to S0-S4 and MRC (medical research council) scale
      respectively. The power of first dorsal interosseous and adductor pollicis was
      used to monitor the recovery of ulnar nerve; and abductor pollicis brevis and
      opponens pollicis for the median nerve. The tendon recovery was evaluated by
      Strickland Adjusted System Score. RESULTS: This study comprised of 10 patients
      (M:F, 4:1), of 14 to 38 years (mean 22.9 years). Injury was accidental in 70%;
      due to broken glass in 50% and kite string in 40%; involving right hand in 70%.
      8.2 (4-12) structures per patient were involved. The injury involved median nerve
      in 70%, ulnar nerve in 60%, (30% had both nerves involved), flexor carpi ulnaris
      in 70%. There was predilection of injury for medial structures. In 80%, wrist
      flexors were involved, and all wrist joints recovered to the full range of
      movements and power. The ulnar nerve showed less total motor and sensory recovery
      than median nerve. However, sensory and motor recovery was good. Overall
      functional results were good and did not correlate with neurophysiological
      studies. CONCLUSION: Immediate primary repair is safe and has good outcome, which
      also depends upon good physiotherapy, close follow-up and patients' compliance.
      Overall clinical and functional assessment is more appropriate than series of
      individual observations and neurophysiological studies.

PMID- 15456552
TI  - Pulmonary hypertension in neonates: does the cause influence the outcome?
AB  - OBJECTIVE: To determine the influence of the cause of pulmonary hypertension in
      neonates on overall outcome. DESIGN: Analytical study. PLACE AND DURATION OF
      STUDY: Special Care Baby Unit (SCBU) at Royal Hospital in Muscat, Sultanate of
      Oman, from July 1998 to June 2003. PATIENTS AND METHODS: All neonates with the
      diagnosis of pulmonary hypertension, based on history, clinical examination and 2
      D echocardiogram were reviewed with respect to the cause of hypertension (primary
      or secondary), birth weight, Apgar score, gender, inborn/outborn and outcome.
      According to the outcome, neonates were divided into two groups, group A
      (survived) and group B (expired). Both groups were compared for described
      variables using Statistical Package for Social Sciences, version 7.5 for Windows
      and Epi Info version 6. RESULTS: Out of 37 neonates with pulmonary hypertension,
      Group A comprised of 22 neonates while group B had 15 neonates, giving a
      mortality of 40 % (15/37). The mean birth weight between the two groups showed no
      significant differences, 3088 +/- 479 gram and 2962 +/- 454 gram, p =0.42,
      respectively. Similarly, no difference in the one and five Apgar scores were
      noted, 4.9 +/- 2.1 and 4.7 +/- 1.3, p = 0.73 and 7.4 +/- 1.5 and 6.7 +/- 1.4, p =
      0.16, respectively. The place of birth had also no significant influence on the
      outcome, however, the cause of pulmonary hypertension was noted to be
      significantly associated with the outcome, p =0.004. CONCLUSION: The cause of
      pulmonary hypertension in neonates does influence the survival. Primary pulmonary
      hypertension in neonates was noted to be associated with poor outcome as compared
      to secondary pulmonary hypertension.

PMID- 15456553
TI  - Symptoms of depression and anxiety in post-myocardial infarction patients.
AB  - OBJECTIVE: To assess the frequency of symptoms of depression and/or anxiety
      following acute myocardial infarction (AMI) and to analyse their association with
      demographic variables. DESIGN: A cross-sectional analytical, non-interventional
      hospital based study. PLACE AND DURATION OF STUDY: The study was carried out at
      Punjab Institute of Cardiology (PIC), Lahore, from January 2000 to January 2001.
      PATIENTS AND METHODS: A total number of 100 inpatients suffering from AMI were
      studied. After a careful selection of the subjects the Urdu version of Hospital
      Anxiety and Depression Scale (HADS) was administered to each patient during the
      period of 5-7 days following AMI to assess symptoms of depression and anxiety. A
      semi-structured clinical interview was also conducted which included demographic
      information, psychiatric history and other variables. Results were analyzed by
      using Statistical Package for Social Sciences (SPSS version 8.0). RESULTS: Out of
      100 subjects, 80 (80%) were males and 20 (20%) were females. Their ages ranged
      from 30-60 years (mean age, 50.92+/-8.53). Overall, symptoms of anxiety and/or
      depression were found in 50 (50%) patients. More specifically, symptoms of
      depression were found in 14%, anxiety symptoms in 18% and mixed symptoms (anxiety
      and depression) in 18% of the patients. Results revealed that patients above 45
      years of age (i.e. 46-60 years) were more likely to experience symptoms of
      depression and/ or anxiety following AMI. A significant association was also
      found between female sex (p <0.02), lower socioeconomic status (p <0.05) and
      symptoms of depression and/ or anxiety in these patients. However, no significant
      association was found in relation to educational status, marital status and
      origin (urban/rural). CONCLUSION: The high proportion of patients with AMI found
      to be suffering from symptoms of depression and/ or anxiety one week after AMI
      highlights the essential need to assess these symptoms in all such patients
      during the post-MI period as they merit appropriate treatment along with the
      other complications of AMI.

PMID- 15456554
TI  - Arteriovenous fistula construction in chronic haemodialysis patients: comparison
      of end-to-side and side-to-side techniques.
AB  - OBJECTIVE: To compare the techniques of end-to-side and side-to-side anastomosis
      in arteriovenous fistulae construction in terms of success rate and immediate
      postoperative complications. DESIGN: Comparative study. PLACE AND DURATION OF
      STUDY: Ayub Hospital Complex, Abbottabad, from October 1999 to December 2002 and
      Khyber Teaching Hospital, Peshawar, from January 2003 to December 2003. PATIENTS
      AND METHODS: One hundred and ninety patients with end stage renal disease (ESRD)
      were included in the study. Arteriovenous fistula was constructed in these
      patients by two techniques i.e. end-to-side and side-to-side anastomosis. The two
      methods were compared in terms of duration of surgery, immediate success rate and
      short-term complications. RESULTS: Among 190 patients, 118 (62%) were males and
      72 (38%) females. The age ranged between 24 to 66 years with average age of 54
      years. Side-to-side anastomosis was done in 120 (63%) patients while end-to-side
      in 70 (37%) patients. The average duration of surgery in side-to-side group was
      50 minutes and in end-to-side group it was 75 minutes. Bleeding occurred in
      4(5.7%) cases in end-to-side group and 2(1.7%) patients in side-to-side group
      requiring re-exploration. The immediate failure rate of the procedure was 2.5% in
      side-to-side group and 7.5% in end-to-side group. Wound infection occurred in
      1(1.4%) case in end-to-side group and 2(1.7%) cases in side-to-side group.
      CONCLUSION: In patients with end stage renal disease (ESRD) arteriovenous fistula
      construction by side-to-side anastomosis is less time-consuming and has less
      complications as compared to end-to-side technique.

PMID- 15456555
TI  - Mortality and morbidity of abdominal inferior vena-caval injuries.
AB  - OBJECTIVE: To evaluate the outcome of abdominal inferior vena-caval (IVC)
      injuries in patients presented to Accident and Emergency Department, Lady Reading
      Hospital, Peshawar. DESIGN: An observational study. PLACE AND DURATION OF STUDY:
      The study was conducted at Postgraduate Medical Institute (PGMI)/Lady Reading
      Hospital, Peshawar, from January 1995 to January 2003. PATIENTS AND METHODS: Case
      records of all patients operated within specified period for vascular trauma
      having injuries to the abdominal inferior vena cava. In all cases vascular trauma
      management was done mainly on clinical assessment in a low equipped set up. Data
      on age, gender, mechanism, nature and location of inferior vena-caval injuries,
      other vascular and non-vascular injuries were recorded. RESULTS: There were 22
      patients, 77.27% male and 22.72% female. Age ranged from 10 to 40 years with mean
      age of 25.09 years. Majority of injuries were caused by penetrating injury
      (77.27%), blunt injury in 04.54% and 18.87% were iatrogenic. Majority (95.45%)
      were having single laceration of inferior vena cava and 04.54% were having more
      than one laceration. Associated vascular injuries involved aortic 9.09%, internal
      iliac in 4.54% and renal vein in 4.54%. Most common associated non-vascular
      injury involved small intestine (72.72%) and large gut (50%). CONCLUSION:
      Inferior vena-caval injuries carries high mortality rate. When associated with
      multiple organ injuries and retrohepatic inferior vena-caval injuries are almost
      fatal.

PMID- 15456556
TI  - Ectodermal dysplasia with acanthosis nigricans (Lelis' syndrome).
AB  - Autosomal recessive ectodermal dysplasia with acanthosis nigricans is termed
      Lelis' syndrome. It is a rare condition and one case is described with overall
      clinical, dermatological and dental findings.

PMID- 15456557
TI  - Unilateral tuberous sclerosis complex.
AB  - Tuberous sclerosis is a rare genetic disease of autosomal dominant inheritance,
      associated with hamartomata formation in several organs and various skin
      findings. A case of young male is presented here with multiple fibromas on right
      side of his face, peri-ungual fibromas in right index and middle fingers and
      right second toe, a small shagreen plaque over right lower back and multiple, ill
      defined hypopigmented patches over his right side of the trunk and right
      buttocks. Fundoscopic examination revealed retinal phacomas on right side. CT
      scan brain showed right-sided paraventricular calcification.

PMID- 15456558
TI  - Chylothorax and chyloascites complicating cirrhosis of liver.
AB  - Chylothorax and chyloascites is the accumulation of chyle in pleural and
      peritoneal spaces and are rarely seen. This case report describes the occurrence
      and management in an old lady. However, she expired due to frank haematemesis and
      encephalopathy. Chylothorax/chyloascites are difficult to manage and associated
      with poor prognosis.

PMID- 15456559
TI  - Colonic perforations in enteric fever.
AB  - We report a case of multiple colonic perforations in a 5-year-old boy due to
      typhoid fever. The main objective is to present the occurrence of this
      complication and discuss the management. The patient was admitted with nine days
      history of high-grade fever and abdominal pain. On examination, he was very sick
      looking child with acute abdomen. After initial workup and resuscitation,
      laparotomy was performed which revealed multiple colonic perforations with feacal
      peritonitis. The case revealed that one must not forget to inspect entire
      intestine including colon, as there may be perforations present in the large
      bowel.

PMID- 15456560
TI  - Progressive hair coil strangulation of penis.
AB  - Strangulation of penis by hair strands is a well-known, but uncommon clinical
      entity. We report two cases occurring in circumcised boys causing progressive
      painless disfigurement of penis with strands of hair coiled around the penile
      shafts, strangulating the penis. Primary repair was done in one case and delayed
      primary repair was done in the other, both with satisfactory results.

PMID- 15456561
TI  - Meta-analysis of new treatment strategies for metastatic colorectal cancer.
AB  - Metastatic disease is present at diagnosis in 30% of the patients with colorectal
      cancer (CRC), and approximately half of early-stage patients with CRC will
      eventually present with metastatic disease. Until recently, few chemotherapy
      options were available to treat metastatic colorectal carcinoma (MCRC).
      Fluorouracil (5-FU) with leucovorin (LV) modulation has a marginal but positive
      effect on survival in those patients. The recent incorporation of irinotecan (CPT
      11) and oxaliplatin for the management of advanced CRC has generated further
      improvement in survival. The development of oral fluoropyrimidines, mimicking
      continuous infusion 5-FU, is convenient to use. Recently completed or ongoing
      clinical trials to study novel targeting agents have initiated a new era of drug
      development. Anti-angiogenesis drugs, tyrosine kinase inhibitors, and epidermal
      growth factor blockers are among the new generation of agents.

PMID- 15456562
TI  - Quinine based combination therapy (QCT): first choice!

PMID- 15456563
TI  - Scoliosis surgery in a patient with chronic myopathy.

PMID- 15456564
TI  - Evaluation of revised trauma score in polytraumatized patients.

PMID- 15456565
TI  - [The professional career in the context of an incentive system. 7 years on: the
      risks of a bureaucratic model].

PMID- 15456566
TI  - [Diagnosing type 2 diabetes mellitus: in primary care, fasting plasma glucose and
      glycosylated haemoglobin do the job].
AB  - OBJECTIVE: To determine the validity of glycosylated hemoglobin (HbA1c) values as
      a method to diagnose type 2 diabetes mellitus (DM2) in a population at risk seen
      in primary care. DESIGN: Cross-sectional analytical study. SETTING: Data were
      obtained for the Raval Sud study population (epidemiologic study of alterations
      in glucose metabolism in a population at risk). PARTICIPANTS: 454 subjects from
      this population (mean age, 65 +/- 3 years; 52% male) at high risk for DM2, seen
      at a primary care center, were included in the study. MAIN MEASURES: We recorded
      demographic data and laboratory values for fasting plasma glucose (FPG), oral
      glucose tolerance test (OGTT), and HbA1c. The diagnostic criteria used for DM2
      were those published by the WHO in 1999. Values for HbA1c were expressed as the
      number of standard deviations (SD) above the mean. RESULTS: Levels of HbA1c
      correlated with FPG (r=0.72) and glucose levels 2 h after oral glucose overload
      (r=0.43). Thirty percent of the patients with FPG between 110 and 125 mg/dL had
      HbA1c values higher than the reference limits. A combined technique based on
      FPG>125 mg/dL or FPG 110-125 mg/dL with HbA1c > or = 3 SD (5.94%) showed a
      sensitivity of 92% and a specificity of 95%. CONCLUSIONS: When FPG is
      inconclusive (110-125 mg/dL), an HbA1c value more than 3 standard deviations
      above the mean (>5.94%) is useful in suggesting a likely diagnosis of diabetes
      and identifying patients who require treatment.

PMID- 15456568
TI  - [Validity of the diagnostic tests for diabetes].

PMID- 15456570
TI  - [Analysis of the relationship between primary care doctors and the pharmaceutical
      industry].
AB  - OBJECTIVES: To describe the type of relationship between primary care family
      doctors (PCDs) and the pharmaceutical industry (PI) and its representatives in
      Aragon, to describe doctors' attitudes to this relationship and to find out how
      doctors behave towards offers from the industry. DESIGN: Descriptive cross
      sectional study, through a self-filled questionnaire with closed replies, of a
      representative sample of the population under study. SETTING AND PARTICIPANTS:
      Family doctors working in primary care teams throughout Aragon. RESULTS: The
      reply rate of 28.17% maintained the study's representativity. Differences in the
      kind of relationship between PCDs and PI were found in gender (greater
      relationship of male doctors) and setting (it was greater in urban areas).
      Doctors working in centres with teaching credentials and woman doctors had a more
      critical attitude. The tendency to collaborate with the industry's offers was
      greater in the rural areas and among men. The group of doctors that interacted
      most with the industry tended to collaborate more with the proposals of the PI.
      No relationship was found between attitude and conduct of PCDs. CONCLUSIONS:
      Results confirm both the starting hypotheses: a) the nature of relationships
      between PCDs and the PI and its representatives affects prescribing behaviour,
      and b) there are differences between what doctors think they should do and what
      they really do in their dealings with the PI.

PMID- 15456571
TI  - [Malnutrition of home care patients].
AB  - OBJECTIVES: To find the nutritional status of people >65 years old included in a
      Home Care programme, using the Mini Nutritional Assessment (MNA), to describe the
      parameters discovered and to identify their relationship with risk factors.
      DESIGN: Descriptive, cross-sectional study. SETTING: Primary care centre.
      PARTICIPANTS: 104 patients, who were over 65 and at the time of the study within
      the centre's home care programme, were included. INTERVENTIONS: The assessment
      was conducted by nursing staff in patients' homes. MAIN MEASUREMENTS: To assess
      the scores on the MNA, to describe the social and demographic variables of
      patients and carers, and to determine the medical, social and pathological
      factors of risk of malnutrition. RESULTS: Patients' mean age was 84.04 (SD,
      8.76). 72.1% of carers were close relatives, with an average age of 61.88 (SD,
      13.53). 20.2% of patients suffered from malnutrition and 51.9% were at risk of
      malnutrition. In both groups there was a low level of autonomy, significantly
      below that of well-nourished patients. No significant differences were found for
      the presence of more chronic illnesses, or social or psychological risk factors
      between these 2 groups and well-nourished patients. CONCLUSIONS: There is an
      extensive risk of malnutrition and actual malnutrition in the home care
      population.

PMID- 15456572
TI  - [Development of children in socially depressed areas of the state of Jalisco].
AB  - OBJECTIVE: To determine the overall development level in children ages 0 to 4 who
      live in very depressed socioeconomic and cultural conditions. DESIGN: This study
      is observational, cross-sectional, and prospective. SETTING: The study was
      carried out in four types of communities in the state of Jalisco, Mexico:
      migrant, indigenous, rural, and irregular urban communities on the outskirts of
      cities. PARTICIPANTS: 1277 children under the age of 4 years, who live in the
      communities selected for the study. PRINCIPAL MEASUREMENTS: Evaluation of the
      overall development level was based on the Jalisco Scale for Evaluation of
      Overall Development, which is designed especially for socioeconomically and
      culturally depressed groups in Mexico. RESULTS: The average development score
      found in the children was 71.7, which is considered moderately low according to
      the 3 classification levels of adequate, moderately low, and low. Only 30.4% of
      the children achieved scores in the adequate category. All the children are
      considered to live in a high-risk psychosocial environment, which explains the
      low scores in overall development as evaluated. CONCLUSIONS: Differences were
      observed in some variables within the uniformly low social level of the subjects
      studied. These differences could be considered as an indication of greater risk
      within a group that is already high-risk. In cases of overall development that is
      very low, mothers do not perceive that children have any problems at the time the
      study is being conducted. This could imply that these mothers do not respond
      proactively to community education and/or health programs that focus on early
      intervention.

PMID- 15456573
TI  - ["Farmaindustrias Code of Good Practice. Very welcome! Now apply it to yourselves
      and improve!"].

PMID- 15456574
TI  - [The professional career of family doctors].

PMID- 15456575
TI  - [Nursing care in prevention and treatment of diabetic foot].

PMID- 15456576
TI  - [LH-RH analogues and myopathy].

PMID- 15456577
TI  - [Differences in intensity of effort between supervised and non-supervised
      exercise of patients with ischaemic cardiopathy].

PMID- 15456578
TI  - [Why in the country do we refer the elderly to hospital casualty departments?].

PMID- 15456579
TI  - [Hypertension emergency as a side-effect of taking NSAIDs].

PMID- 15456580
TI  - [Some thoughts on primary care and ill-treatment of women].

PMID- 15456582
TI  - [Research in primary care pediatrics: a neglected topic].

PMID- 15456583
TI  - [Socioeconomic status and resource consumption in primary care].
AB  - OBJECTIVE: To determine the influence of socioeconomic status on healthcare
      demand and resource consumption in our population. PATIENTS AND METHODS: We
      performed a cross sectional, retrospective study of socioeconomic status and
      healthcare and pharmaceutical consumption in randomly selected patients from five
      primary care pediatric clinics in Madrid. The chi-square test was used to compare
      percentages. For the remaining analyses, nonparametric tests were used after
      confirming that the data followed non-normal distribution. RESULTS: We compared
      684 questionnaires. Patients in the most disadvantaged socioeconomic levels
      consumed a greater number of drugs than those in more privileged levels (mean
      0.79 vs. 0.47, p = 0.04). The mean pharmacological expenditure was also higher in
      the lowest socioeconomic levels than in the highest levels (5.28 Euros vs. 2.21
      Euros, respectively; p = 0.001). No significant differences were found among
      socioeconomic levels in the number of consultations or diagnostic tests
      requested. The number of consultations was higher in younger patients (p < 0.001)
      or in those with chronic diseases (p = 0.001). Drug consumption was increased in
      the most disadvantaged levels (p = 0.002) and in patients with chronic diseases
      (p < 0.001). Lastly, pharmacological expenditure expressed in Euros was also
      higher in the lowest socioeconomic levels (p = 0.001) and in patients with
      chronic diseases (p < 0.001) but was lower if one of the parents was a foreigner
      (p = 0.031). CONCLUSIONS: We found a relationship between socioeconomic level and
      drug consumption and its attributable cost. These data should be confirmed by
      broader studies.

PMID- 15456584
TI  - [Antibiotic use in primary care. Do we know what parents think?].
AB  - INTRODUCTION: In Spain, studies that investigate parents' beliefs on antibiotic
      use are lacking. Mistaken beliefs lead to inappropriate antibiotic use and
      encourage overuse. The aim of the present study was to determine parents'
      knowledge about antibiotic use. MATERIAL AND METHODS: We performed a cross
      sectional, descriptive study in two health centers through a self-administered
      questionnaire completed by 348 parents. The response variable consisted of
      beliefs evaluated when the parents answered the following three statements in the
      affirmative: a) there are currently some infections with inadequate response to
      antibiotic treatment; b) if antibiotics are used too often, they can cease to
      have an effect; c) if your child frequently receives antibiotic treatment,
      subsequent use may have no effect. Independent variables consisted of sex of the
      responder, educational level, parental age and ethnicity, attendance at school
      (public or private), attendance at kindergarten, usual healthcare (public
      private), and number of siblings. Statistical analysis consisted of logistic
      regression. RESULTS: A total of 31.6 % (95 % CI: 26.7-36.5) responded
      affirmatively to the three statements. Adequate knowledge was associated with the
      non-immigrant population (OR: 5.7; 95 % CI: 1.37-24.9) and high parental
      education (OR: 2.04; 95 % CI: 1.16-3.06). CONCLUSIONS: Parents' knowledge of
      antibiotic use is low compared with that in other countries. Health education
      programs to remedy this situation are urgently required.

PMID- 15456585
TI  - [Meningococcal sepsis in pediatrics. Parameters associated with poor outcome].
AB  - BACKGROUND: Mortality due to meningococcal sepsis continues to be extremely high.
      Patients with a poor prognosis require aggressive therapy and should be
      identified early. OBJECTIVE: To investigate the clinical and biological factors
      associated with poor outcome. PATIENTS AND METHOD: Seventy-one children aged 2
      months to 13 years with meningococcal sepsis were studied. Inclusion criteria
      were meningococcus isolation in cultures or characteristic clinical features with
      purpuric exanthema. METHODS: A correlational descriptive study was performed. In
      all patients we evaluated the Pediatric Risk of Mortality (PRISM), the Glasgow
      Scale for Meningococcal Sepsis (GSMS), polymorphonuclear (PMN) count and
      prolactin (PRL), leptin (LPT) and C-reactive protein (CRP) levels. RESULTS:
      Fourteen children (19.7 %) died. Death was associated with multiple organ
      dysfunction syndrome (MODS) (p = 0.0001), high GSMS and PRISM scores (p = 0.0001)
      and to a lesser extent with shock (p = 0.01). In patients who died, the
      determinations showing greatest alteration at admission were PRL levels (p =
      0.0009) and PMN count (p = 0.0005). CRP levels were not associated with
      differences in mortality but were high in patients with shock (p = 0.008).
      Children with high body weight percentiles were at greater risk of death and
      showed higher levels of PRL, PCT (p = 0.006) and LPT (p = 0.006), without
      differences in GSMS or PRISM scores. Age did not influence mortality or PRL
      levels but did influence GMSM and PRISM scores and PMN and CRP levels. These
      differences disappeared after the age of 2-3 years. In patients with MODS or
      shock, the only differences found were reduced PMN count (p = 0.0001) and
      elevated PRL levels (p = 0.0001). CONCLUSIONS: In meningococcal sepsis, death is
      more frequent in children with high body weight percentiles. Moreover, these
      children present elevated PRL and LPT levels, although whether these variables
      act independently remains to be elucidated.

PMID- 15456586
TI  - [Fiberoptic bronchoscopy in childhood endobronchial tuberculosis].
AB  - BACKGROUND: Endobronchial tuberculosis is a classical manifestation of primary
      tuberculosis in childhood. Fiberoptic bronchoscopy (FB) is an ancillary
      diagnostic tool, but its utility and indications are not well established.
      OBJECTIVES: To analyze the FB performed over 11 years (1992-2003) in children
      with a diagnosis of tuberculosis and to review the literature. A further aim was
      to establish the current usefulness of FB in children with tuberculosis and
      propose criteria to determine the indications for FB in this population. METHODS:
      We report a retrospective series (n 5 16). FB was indicated in children who
      showed any of the following findings in chest roentgenogram: a) persistent
      parenchymal consolidation; b) lymphadenopathy and consolidation; c)
      hyperinsufflation (emphysema); d) atelectasias, and e) airway narrowing caused by
      lymphadenopathies. Published series on the topic were reviewed and six studies
      were suitable for comparison with our own. RESULTS: Endobronchial tuberculosis
      was found in seven children (43 %) and extrinsic compression was found in three
      (18 %). The microbiological results obtained from FB samples were not superior to
      those obtained from classical diagnostic methods. The sensitivity of the proposed
      criteria for suspicion of endobronchial tuberculosis was 71 %. Endoscopic
      findings justified a change in therapy in 50 % of the children (addition of
      corticoids or surgery) and this percentage was similar to that reported in other
      series. CONCLUSIONS: FB does not usually improve microbiological diagnosis of
      tuberculosis but can be useful when choosing the most appropriate therapy in
      children with suspected endobronchial tuberculosis. In some cases, computed
      tomography may make FB unnecessary, but in others this procedure can be
      therapeutic (obstruction due to caseum, atelectasias). Establishing the
      indications for FB in childhood tuberculosis is difficult, but the proposed
      criteria may be an acceptable guide to identifying which patients could benefit
      most from this procedure. Not all children with endobronchial tuberculosis
      require corticoids.

PMID- 15456587
TI  - [Beta-cell, thyroid and celiac autoimmunity in children with type 1 diabetes].
AB  - OBJECTIVE: The aim of this study was to evaluate the presence of beta-cell,
      thyroid and coeliac autoimmunity in children with recent-onset type 1 diabetes.
      METHODS: We studied all children with newly diagnosed type 1 diabetes. Data were
      analyzed from 63 children aged 2-14 years who were treated in the Department of
      Pediatrics of the Virgen de las Nieves University Hospital in Granada (Spain)
      from 1998-2002. Antibodies to glutamic acid decarboxylase-65 (GADA), anti-insulin
      (AIA), thyroperoxidase (anti-TPO), thyroglobulin (anti-TG), thyroid-stimulating
      immunoglobulins (TSI) and endomysial antibodies (EmA-IgA) were measured and
      documented. A total of 55.5 % of these patients were girls and the mean age was
      7.9 +/- 3.2 years. RESULTS: The prevalence rates were: GADA 65.1 %; AIA 68.3 %;
      anti-TPO 11.1 %; anti-TG 9.5 %; TSI 4.8 % and EmA-Ig A 3.1 %. Children with
      thyroid antibodies (anti-TPO1) were significantly older and developed diabetes
      later in life (P < 0.05) than those without antibodies. Thyroid-stimulating
      hormone levels, goiter and thyroid dysfunction were higher in children who were
      anti-TPO1 than in diabetic children without thyroid autoimmunity. CONCLUSIONS:
      Children with newly diagnosed type 1 diabetes show a high prevalence of thyroid
      and coeliac autoimmunity. In cases of positivity, additional work-up and
      intervention are advocated. These measures can prevent the well-known
      complications of diabetes and improve its clinical course.

PMID- 15456588
TI  - [Echogenic material in fetal gallbladder: prenatal diagnosis and postnatal follow
      up].
AB  - OBJECTIVE: To study the prevalence of echogenic material in fetal gallbladder and
      to analyze its pathological relevance, the perinatal factors involved and the
      postnatal outcome of detected cases. PATIENTS AND METHODS: We performed a
      prospective study of ultrasonographic examination of 9235 fetuses in the third
      trimester of gestation. Perinatal data were collected. Postnatal ultrasonography
      was performed in identified cases. RESULTS: Fetal biliary echogenic material was
      found in 0.45 % of all pregnancies, with 42 identified fetuses. A single
      echogenic image was found in four fetuses (9 %), two or more echogenic images
      were found in seven fetuses (17 %) and biliary sludge was found in 31 fetuses (74
      %). All diagnoses were made between weeks 29 and 38 of gestation. No link was
      found with maternal factors or perinatal abnormalities. Postnatal follow-up was
      carried out in 39 neonates; of these, five neonates (13 %) showed biliary sludge,
      although all five were asymptomatic. In further follow-up examinations,
      ultrasound studies were normal. CONCLUSIONS: Fetal biliary echogenic material was
      found in one out of every 200 fetuses. No relationship was found with perinatal
      abnormalities. The prognosis of fetal gallstones and biliary sludge is favorable.

PMID- 15456589
TI  - [Pediatric palliative care: a comprehensive model of care for children with life
      threatening conditions and their families].
AB  - The present article reviews aspects unique to pediatric palliative care: the
      attitudes of medical staff toward pediatric death and life-threatening
      conditions, distinct patterns of pediatric deaths, the causes of suffering in
      children with life-threatening conditions and their families, and the features
      that make palliative care a challenge for children, families, medical staff and
      society. Concepts of pediatric palliative care and various approaches are
      described. In addition, Universal Principles of Pediatric Palliative Care are
      presented. Special attention is paid to approaches that start palliative care at
      diagnosis of a life-threatening conditions, do not require a short-term life
      prognosis and do not exclude curative or life-prolonging therapies since these
      approaches can benefit both children who survive life-threatening conditions and
      those who die, as well as their families. The need for certain changes through
      education and research is proposed to improve the quality of life of children and
      families who currently suffer, satisfaction and cohesion among medical staff, and
      healthcare quality.

PMID- 15456590
TI  - [Trisomy 9p. Report of two new cases].
AB  - Trisomy 9p is a chromosome abnormality caused by duplication of the short arm of
      chromosome 9. Clinically it is characterized by psychomotor retardation,
      malformations that can affect various organs and sometimes epilepsy. Trisomy 9p
      may be the fourth most common autosomal trisomy, after trisomies 21, 13 and 18.
      Two new cases of trisomy 9p are described. Previous cases reported in Spain,
      associated clinical features, and the diagnostic and therapeutic approach to
      these patients are revised.

PMID- 15456591
TI  - [Hypernatremic dehydration associated with breast-feeding].
AB  - BACKGROUND: During the last 10 years the number of publications reporting a rise
      in the incidence of hypernatremia in children who are exclusively breast-fed has
      increased. OBJECTIVE: To report the results of a series of cases detected in a
      district hospital in the last 6 years in order to better delineate the clinical
      characteristics of infant hypernatremia, its optimal treatment and preventive
      measures. MATERIAL AND METHODS: The selection criteria for our study included all
      neonates aged less than 30 days with serum sodium concentrations equal to or
      greater than 150 mEq/mL who were exclusively breast fed. Cases were identified
      through the departmental database. RESULTS: Twelve newborns were identified who
      presented the following characteristics: mean gestational age of 39.5 weeks, mean
      birth weight of 3440 grams, mean percentage of weight loss from birth 13.7 % and
      mean serum sodium value 152.75 mEg/mL. Five neonates (42 %) were admitted from
      the maternity unit and seven (58 %) from the emergency department. The presenting
      complaints included weight loss in nine infants, irritability in six, fever in
      six, poor feeding in five and jaundice in two. Most of the neonates had more than
      one symptom. Ten of the mothers (83.33 %) were primiparous and two (16.67 %) were
      secundiparous. CONCLUSIONS: Hypernatremia due to breast-feeding is a consequence
      of inadequate breast-feeding technique in inexperienced mothers. A possible
      solution would be for health professionals to provide mothers with greater
      support.

PMID- 15456592
TI  - [International adoption in Russia. An added risk?].

PMID- 15456593
TI  - [Inflammatory tinea manuum].

PMID- 15456594
TI  - [Hereditary angioedema with exclusive abdominal presentation. What is the
      therapeutic approach?].

PMID- 15456595
TI  - [Determinants of plasma homocysteine concentration].

PMID- 15456597
TI  - [Poland's sequence and dextrocardia].

PMID- 15456598
TI  - [Calcification of intervertebral disks in childhood].

PMID- 15456599
TI  - [Erythroderma and hepatitis].

PMID- 15456600
TI  - [Bone Paget's disease in the young adult].

PMID- 15456601
TI  - [A study of interconsultations requested to an Internal Medicine Department].
AB  - BASIS: The medical interconsultation contributes knowledge of a speciality to
      another one, but implies an important workload. The objective is to define de
      characteristics of medical interconsultation requested to an Internal Medicine
      Department and to assess the workload that they involve. PATIENTS AND METHOD:
      Medical interconsultations requested during 6 months were included. Sex and age
      of the patient, petitioner department, reason for the interconsultation, follow
      up length and referring to other departments were evaluated. RESULTS: 181 medical
      interconsultation were requested, 53.6% were women. Median age was 68.5 years (17
      98), and median follow-up was 6 days (1-76). Surgical departments requested
      86.7%. The reason was long pathology in 19.7% and cardiac pathology in 18.9%.
      There was more than one reason in 53 medical interconsultations. Twelve patients
      were referred to other departments. CONCLUSIONS: Most of medical
      interconsultations come from the surgical area. The differences among the
      petitioner departments are due to their different kind of organization and
      staffing of to the different types of formation or criteria of requestion
      physicians. Cardiopulmonary pathology predominates, possibly because of high
      prevalence of this pathology in the hospital. The workload due to medical
      interconsultation is similar to workload internists endure in their
      hospitalization area.

PMID- 15456602
TI  - [Distinguishing pleural transudates and exudates through the quantification of
      biochemical parameters].
AB  - OBJECTIVES: 1) to evaluate the possibility of distinguishing pleural transudates
      and exudates through the joint determination of 26 biochemical parameters in
      pleural effusion and in plasma (including the determination of high molecular
      weight proteins, acute phase reactants, and proinflammatory citokines), and 2) to
      formulate a logistic regression equation for optimizing the classification
      efficiency, comparing the equation obtained with Light's criteria. PATIENTS AND
      METHODS: All diagnostic thoracocentesis carried out in La Rioja Autonomous
      Community during a 22-month period were evaluated. The 245 clinical records were
      evaluated periodically along a minimum of 2 years, after the discharge of the
      patients. In pleural effusion and in plasma the following were quantified: total
      proteins, LDH, glucose, amylase, cholesterol, albumin, cholinesterase,
      phosphatase alkaline, urea, beta2-microglobulin, IgG, IgM, alpha2-macroglobulin,
      C reactive protein, transferrin, alpha1-antitrypsin, serum amyloid A protein,
      interleukin 1-beta, interleukin 6, tumoral necrosis factor-alpha, and lysozyme.
      In addition, the cellularity, polymorphonuclear elastase and adenosine deaminase
      were evaluated in pleural fluid. RESULTS: The LDH pleural effusion/plasma ratio
      was the individual parameter that showed higher area under the receiver operating
      characteristic curve for the separation of pleural transudates and exudates.
      Interleukin 6 and tumoral necrosis factor-alpha showed pleural effusion/plasma
      ratios higher than the unit, which suggests an in situ citokines production. An
      predictive logistic regression equation was obtained that incorporates only LDH
      and cholesterol ratios, including the diuretic treatment of the patient at the
      time of thoracocentesis, which did not modify the protein concentrations in
      pleural effusion. Except for LDH ratio, the logistic regression equation showed
      an area under the receiver operating characteristic curve higher than that of all
      the evaluated individual parameters, with a sensitivity of 95% and a specificity
      of 85% (70% for the Light's criteria). CONCLUSIONS: LDH ratio is the best
      individual parameter for distinguishing pleural transudates and exudates. The
      additional evaluation of cholesterol ratio and of the diuretic state of the
      patient make possible to improve the clinical efficiency of this classification.
      The quantification of high molecular weight proteins, acute phase reactants and
      citokines does not contribute additional significant information.

PMID- 15456603
TI  - [Acute lung embolism: a prospective study from May 1992, to May 2002].
AB  - INTRODUCTION: To define de prevalence, the clinical profile, the predisposing
      factors and the hospital evolution of clinical acute lung thromboembolism
      episodes. MATERIAL AND METHODS: A prospective study from May 1992, to May 2002,
      of acute lung embolism in an Internal Medicine ward with 8 beds in Hospital of
      Navarra (EPHONA). Clinical acute lung thromboembolism is defined by the clinical
      characteristics together the demonstration of thrombi in the lung arteries with
      arteriography, helicoid computerized axial tomography, or high or average
      probability lung gammagraphy, together the demonstration of deep venous
      thrombosis with doppler ultrasound or phlebography. We compared the clinical
      spectrum with that of international clinical series, evaluated the possibility of
      clinical syndromes according to the size of the affected vessel (central vs.
      peripheral), and compared the characteristics of patients with manifest deep
      venous thrombosis with those of the patients with clinical acute lung
      thromboembolism and without a known emboli source. RESULTS: In the period of 10
      years, and with 2,493 patients admitted, 106 clinical acute lung thromboembolism
      were diagnosed (prevalence: 4.25%; CI: 3.51-5.14; p < 0.05); these patients were
      72 +/- 11 years, in other words, an age 5 years higher than the rest of the
      patients (p < 0.001). There was a delay of 10 days from the beginning of the
      symptomatology up to the hospitalization. The clinical spectrum was similar to
      that of other reported series except by the presence of cough and pleural rub (p
      < 0.001). The main predisposing factors were immobility (41%) and cancer (25%).
      Hospital mortality was 3.77%. In 70 (66%) patients we obtained information on the
      affected vessel, not being fulfilled the association of specific clinical
      syndromes with the size of the vessel, although the patients with central
      clinical acute lung thromboembolism showed higher deterioration of gas exchange
      (p = 0.002) and higher activation of the fibrinolysis (p = 0.012) than patients
      with peripheral clinical acute lung thromboembolism. 35% of episodes of clinical
      acute lung thromboembolism developed without simultaneous deep venous thrombosis
      and showed higher disturbance of gas exchange (p = 0.03) and arterial hypotension
      (p = 0.02). CONCLUSIONS: Clinical acute lung thromboembolism is a frequent
      condition that occurs in patients of advanced age and that shows low hospital
      mortality when is diagnosed and treated even with a 10-day delay up to the
      diagnosis. The clinical spectrum is similar to that observed in other parts of
      the world, but the cough as a prominent a symptom and the pleural rub should
      propose other diagnostic alternatives. The size of the affected pulmonary vessel
      is not related with a specific clinical syndrome, although the central clinical
      acute lung thromboembolism evolves with higher disturbance of the gas exchange.
      In the third of clinical acute lung thromboembolism episodes an emboli source is
      not demonstrated, perhaps because all emboli has migrate to the pulmonary
      arteries; these episodes give rise to higher hypotension and disturbance of the
      gas exchange.

PMID- 15456604
TI  - [Pulmonary hemorrhage and anti-phospholipid syndrome].
AB  - The presence of anti-phospholipid antibodies (anticardiolipin antibodies and
      lupus anticoagulant) associated to venous and/or arterial thrombotic phenomena
      and fetal losses define the anti-phospholipid syndrome. On rare occasions severe
      hypoprothrombinemia associated with this disease as a cause of hemorrhagic
      manifestations has been described. In addition very few cases of alveolar
      hemorrhage in anti-phospolipid syndrome (APS) have been described, being this
      complication usually related to microthrombosis and/or capillaritis of pulmonary
      vessels. We describe two patients without previous clinical manifestations of
      anti-phospholipid syndrome that showed pulmonary hemorrhage with anticardiolipin
      antibodies positivity. The first of them, a 33-year-old male, began his disease
      with low prothrombin time and the presence of antiprothrombin antibodies. In the
      biopsy by thoracoscopy the presence of pulmonary hemorrhage without capillaritis
      nor thrombotic phenomena was demonstrated, becoming evident certain clinical
      improvement and normalization of the prothrombin time after receiving
      immunosuppressive treatment but with persistence of the pulmonary hemorrhage 5
      years later. The second case, a 89-year-old male, began his condition with
      bilateral lung infiltrates and hemoptysis, anticardiolipin antibodies positivity,
      and thrombopenia, with recurrence of the condition 1 year later. After other
      etiological possibilities were ruled out, and despite hemorrhagic trait in both
      patients, we consider that they should be in the clinical context of the anti
      phospholipid syndrome, although at this time they did not meet the criteria
      recognized in order to diagnose this disease. Within the ampliable clinical
      spectrum of the anti-phospholipid syndrome we should take into account the
      pulmonary hemorrhage.

PMID- 15456605
TI  - [Bone Paget's disease in the young adult].
AB  - FOUNDATION: Bone Paget's disease (BPD) is a focal disorder of bone remodeling of
      unknown etiology that affects mainly patients older than 50 years. BPD is after
      osteoporosis the most frequent osteopathy of the western world and was described
      for the first time in 1876 by Sir James Paget who called it osteitis deformans.
      PATIENTS AND METHODS: We present two patients with BPD younger than 40 years. In
      this report their clinical, analytical, diagnostic, and therapeutic
      manifestations are described, with the findings of bone biopsy in one of them. Is
      noteworthy to us the younger age of the patients, rare for this disease, which
      means that we have carried out the follow-up of the cases. CONCLUSION: In a young
      adult with high phosphatase alkaline values we will include BPD in the
      differential diagnosis.

PMID- 15456606
TI  - [Food allergy].

PMID- 15456607
TI  - [Oral component in Sjogren's syndrome. Diagnostic and therapeutic
      recommendations].

PMID- 15456608
TI  - [Anorexia treatment in the oncological patient].

PMID- 15456609
TI  - [Complete heart blockade, external ophthalmoplegia, and pigmentary retinitis].

PMID- 15456610
TI  - [Cervical cellulitis and pyomyositis in a diabetic].

PMID- 15456611
TI  - [Pulmonary artery sarcoma].

PMID- 15456612
TI  - [A lung image with cavitation].

PMID- 15456613
TI  - [The role of intestinal absorption blockade in hypercholesterolemia treatment].
AB  - Mechanisms of biliary and diet cholesterol absorption are reviewed, and the
      characteristics of a new specific intestinal cholesterol absorption inhibitor
      (ezetimibe) are discussed. Ezetimibe is absorbed well by oral route, shows
      glucuronization in the liver and enters in enterohepatic circulation; thus, half
      life is long, around 22 hours. Dose is 10 mg administered once a day. Ezetimibe
      works through both cholesterol sources: the production of cholesterol by
      hepatocytes and the absorption of cholesterol by enterocytes, giving rise in this
      way to an additive hypolipemic effect. The administration of lower dose of statin
      besides 10 mg of ezetimibe amounts to the administration of highest dose of
      statin. In patients who take statins whose LDL cholesterol levels are higher than
      normal, adding ezetimibe increase from 27% to 75% the percentage of those who
      reach the therapeutic objective. In addition to increasing the effectiveness,
      side effects are also avoided since the tolerability to ezetimibe is similar to
      placebo. The average maximum reduction of the plasma level of cholesterol with 10
      mg of ezetimibe and 80 mg of simvastatin or atorvastatin is higher 60%.

PMID- 15456614
TI  - [Methicillin-resistant Staphylococcus aureus infectious spondylitis].

PMID- 15456615
TI  - [Cushing's syndrome: a case of resectable schizophrenia].

PMID- 15456616
TI  - [Age, comorbidity, and mortality in patients hospitalized because of community
      acquired pneumonia].

PMID- 15456617
TI  - [Tuberculin test and latent tuberculous infection treatment].

PMID- 15456618
TI  - Gastroesophageal reflux and asthma.

PMID- 15456619
TI  - [Proliferative response of peripheral blood mononuclear cells to the recombinant
      allergen BtM of the Blomia tropicalis housedust mite].
AB  - Allergic diseases are triggered when individuals genetically predisposed to
      developing an allergy (atopy) are exposed to sensitizing allergens. These
      allergens are captured and processed by antigen-presenting cells (APC) which
      presents them to T lymphocytes. Some of these allergens have a significant
      influence on the development of this type of disease and cause most of the
      symptoms in allergic individuals around the world. They are found in the feces of
      house dust mites, which have diverse and varied origin in several species, for
      example the Blomia tropicalis (Bt) mite. In Cartagena (Colombia), this highly
      prevalent mite has been a central object of study by the Institute of
      Immunological Research of the University of Cartagena, where several of its
      allergens have been cloned, sequenced and expressed as recombinant allergens.
      Moreover, their capacity to bind to IgE and the frequency of this process has
      been studied. The aim of the present study was to analyze the lymphoproliferative
      response of peripheral blood mononuclear cells (PBMC) in healthy and allergic
      individuals to one of the recombinant allergens of B. tropicalis, BtM. This
      response was studied in PBMC from six patients with allergy to Bt (positive
      cutaneous test to Bt extract), using a cellular proliferation technique, with
      incorporation of 3H thymidine at days 3 and 6 days of culture, and at three
      different concentrations of BtM. Notable among the results was the high
      proliferation produced by cells from patient JF018 at 3 days of stimulus (41.7
      IE), with the lowest concentration of protein (100 microg/mL). Moreover, in all
      the experiments this concentration was the cause of most of the cell
      proliferation. In addition, some response to control LAC012 against glutathione-S
      transferase (GST) was induced. In conclusion, the results of the present study
      demonstrate that the recombinant allergen BtM is able to induce a cellular
      response in the PBMC of patients allergic to Bt. Moreover, it is able to induce a
      response similar to that produced by natural allergens, because its pattern of
      response is similar to that shown by cells stimulated with Bt extract. These
      results also show that a process of anergy can be produced in cells when excess
      antigen is present. In some individuals (both allergic and nonallergic), GST is
      able to cause a proliferative response, indicating its sensitizing potential in
      these individuals.

PMID- 15456620
TI  - Different lymphocyte markers and cytokine expression in peripheral blood
      mononuclear cells in children with acute atopic dermatitis.
AB  - BACKGROUND: The pathogenesis of atopic dermatitis (AD) is still not completely
      understood. AD is characterized by the presence of clinical symptoms of both IgE
      antibody-mediated immediate hypersensitivity and specific T lymphocyte-mediated
      delayed hypersensitivity. OBJECTIVE: To evaluate the immunological mechanisms
      involved in children with acute AD lesions. MATERIAL AND METHODS: Ten children
      with acute AD lesions and 10 non-atopic controls were studied. Total IgE was
      measured by immunoassay. T cell marker expression (CD3, CD4, CD8, cutaneous
      lymphocyte-associated antigen [CLA]) and cytokine production (interferon [IFN]
      gamma, interleukin [IL]-13) were analyzed in peripheral blood mononuclear cells
      by flow cytometry. RESULTS: In children with AD the percentage of CD3+ cells (p =
      0.015) increased while that of CD8+ cells (p = 0.023) decreased, with no
      differences in CLA expression. We found increased IL-13 production in CD3+ cells
      (p = 0.01) and CD3+CD4+ (p = 0.001) cells with no difference in IFN-gamma. Total
      IgE was significantly higher in patients with AD (p = 0.01). Comparison of IL-13
      production in CD4+ cells categorized by total IgE level showed that IL-13
      production was significantly increased in subjects with a higher IgE level.
      CONCLUSION: Peripheral blood from children with AD showed an increase in IgE
      levels and a Th2 pattern. There was a correlation between IL-13 production and
      total IgE levels.

PMID- 15456621
TI  - Quality of life in pediatric patients with asthma with or without obesity: a
      pilot study.
AB  - BACKGROUND: In addition to the increased incidence of asthma, obesity in
      asthmatic children is also on the rise. Several studies have been performed to
      determine whether obesity could be a risk factor for asthma, but this association
      has not been demonstrated in all patients. The Pediatric Asthma Quality of Life
      Questionnaire (PAQLQ) is a standardized and validated tool for use in the
      pediatric population, which evaluates the effect of asthma on patients' daily
      activities. METHODS AND RESULTS: To determine the effect of obesity and
      overweight on quality of life, the PAQLQS was applied to 100 pediatric patients
      with intermittent asthma and mild persistent asthma and obesity, overweight and
      normal weight. The results of the three dimensions evaluated in the questionnaire
      (emotions, symptoms and limitation of activities) showed significant differences
      in quality of life in the obese asthmatic group only (p < 0.000). No differences
      were found when the groups with and without overweight were compared.
      CONCLUSIONS: The PAQLQ revealed a significant difference in the quality of life
      in obese asthmatic patients. Overweight and normal weight had no effect quality
      of life.

PMID- 15456622
TI  - [Diagnostic considerations in unilateral hyperlucency of the lung (Swyer-James
      MacLeod Syndrome)].
AB  - Swyer-James-MacLeod Syndrome (SJMS) is considered to be a relatively uncommon and
      complex disease characterized by roentgenographic hyperlucency of one lung, lobe,
      or part of a lobe, due the pulmonary vascular structure and alveolar
      overdistension. It is sometimes associated with bronchiectasis. This syndrome
      seems to be an acquired disease that develops after viral bronchiolitis and/or
      viral pneumonia in early childhood. Microscopically, there is evidence of patchy
      bronchitis and bronchiolitis.SJMS is usually asymptomatic and discovered
      accidentally by chest radiography in a child with respiratory symptoms and should
      be differentiated from other causes of unilateral hyperlucency on chest
      radiography, such as those related to congenital bronchial and/or vascular
      abnormalities. Treatment includes early control of lung infections, as well as
      influenza and pneumococcal vaccination. Few reports of this syndrome in children
      have been published. We describe the case of a 12-year-old boy with unilateral
      hyperlucency of the lung and respiratory symptoms of acute pneumonia and discuss
      the main diagnostic features of this syndrome.

PMID- 15456623
TI  - Tolerance and short-term effect of a cluster schedule with pollen-extracts
      quantified in mass-units.
AB  - We performed a prospective, multicenter study to assess the tolerance and
      possible short-term effects of allergen vaccines administered according to a
      cluster schedule in the months immediately preceding the onset of the pollen
      season. The study was carried out in eight centers and included 191 patients
      (children and adults) with allergic respiratory disease due to sensitization to
      olive tree and/or grass pollen. Of these, 34 patients acted as controls and the
      remaining patients received immunotherapy administered in the initiation phase
      according to a cluster schedule of eight doses injected on four visits. After 3
      months of treatment, significant differences were found between the two groups in
      medication consumption (antihistamines in drops and oral formulations: p = 0.045
      and p = 0.001, respectively; short-acting beta2-agonist treatments: p = 0.004)
      and respiratory symptoms (wheezing and coughing: p = 0.035 and 0.014,
      respectively). The cytokine profile (interleukin [IL]-4, 5, 10 and 2, interferon
      [IFN-gamma], and tumor necrosis factor [TNF-alpha]) was determined before the
      start of treatment and at the end of follow-up (4-5 months). Levels of IL-4, 5
      and 10 (Th2 profile) decreased while those of IL-2, IFN-gamma, and TNF-alpha (Th1
      profile) decreased. These differences were more marked in the active group than
      in the control group but were not statistically significant. No severe adverse
      effects were recorded. This study shows that the schedule tested had an
      acceptable tolerance profile and produced significant changes in symptom and
      medication scores after a few months of treatment. A double-blind, placebo
      controlled study is needed to confirm these results.

PMID- 15456624
TI  - A prospective safety study of allergen immunotherapy in daily clinical practice.
AB  - BACKGROUND: Despite its clinical effectiveness, allergen immunotherapy (AIT)
      remains controversial because serious systemic reactions can occur during its
      administration. Most of the studies on the safety of AIT are retrospective and
      use different methods, which frequently depart from daily clinical practice.
      OBJECTIVE: The aim of this study was to determine risk factors for adverse
      reactions, especially systemic adverse reactions, produced during routine AIT
      administration. METHODS: We registered 5,768 consecutive doses of standardized
      extracts administered to 273 patients in conventional schedules, following the
      recommendations on safety and data collection of the European Academy of
      Allergology and Clinical Immunology. Of the 273 patients, 236 were asthmatics, 28
      had rhinitis and 9 received immunotherapy due to Hymenoptera anaphylaxis.
      RESULTS: We examined 143 local reactions (2.48 % of the doses) and 145 systemic
      reactions (78 immediate and 67 delayed). Risk factors for developing an immediate
      systemic reaction were asthma severity, sensitization to molds, the most
      concentrated vials and a fall in peak expiratory flow of more than 15 % or an
      immediate systemic reaction in the previous dose. Late systemic reactions were
      significantly more frequent with less concentrated vials and in patients with
      late local reactions in the previous dose. No serious reactions were registered.
      CONCLUSIONS: We believe that AIT is reliable when used with strict safety
      protocols and administered by specialized staff. Risk factors for adverse
      reactions to this type of treatment can be identified and reduced by systematic
      data collection.

PMID- 15456625
TI  - [Application of immunotherapy in Catalonia (Spain)].
AB  - BACKGROUND: The aim of this study was to determine the use of specific
      immunotherapy (SIT) in public and private hospitals in Catalonia (Spain) in the
      management of respiratory allergic diseases and opinions about this treatment
      through a questionnaire. SIT dosage schedules and the creation of immunotherapy
      units were also investigated. METHODS AND RESULTS: A questionnaire containing
      eight items was sent by post and/or electronic mail to the heads of allergy units
      in 24 public and private hospitals in Catalonia.A total of 18 hospitals
      responded. The most commonly used route of administration was subcutaneous (89.4
      %, SD 9.05) and the most widely used dosage schedule was the classical schedule
      (77.2 %, SD 24.9). Most of the hospitals (83.3 %) believed that immunotherapy
      units were an advantage but only 44 % of them believed that their creation was
      feasible. CONCLUSIONS: The results of this survey identify the application of SIT
      in Catalonia and reveal certain features of this treatment that remain to be
      established such as the optimal dosage schedule and the precautions that should
      be followed when administering SIT.

PMID- 15456626
TI  - Use of alternative medicines by allergic patients in Turkey.
AB  - BACKGROUND: Although complementary and alternative medicines are frequently used
      in Turkey, no studies with large series have yet been published. OBJECTIVE: Our
      aim was to determine the prevalences of the use of various types of complementary
      and alternative medicines in patients with asthma, seasonal allergic rhinitis
      (SAR) and chronic urticaria (CU) and the relationship between the use of these
      substances and patients' social, economic and demographic characteristics.
      METHODS: All patients completed a questionnaire about the use of complementary
      and alternative medicines, including herbal products, animal products,
      acupuncture, yoga, massage therapies, Turkish-baths, speleotherapy, and
      psychoreligious methods for curing their diseases. RESULTS: The overall use of
      complementary and alternative medicines was 38 %. The most common alternative
      therapy treatment was herbal therapy (30.5 %). The prevalence of the use of these
      therapies was higher in asthmatics than in patients with SAR and CU. In all
      patients, variables associated with the use of these therapies were older age and
      having asthma. Among asthmatics, the use of these therapies within the previous
      12 months was higher in patients with hospitalization and acute attacks than in
      those without hospitalization or acute attacks. In this group important
      covariates in the use of complementary and alternative medicines were older age
      and severe disease. Approximately half of the patients and 41.2 % of asthmatics
      discontinued pharmacological therapy during alternative treatment or had not yet
      started it. CONCLUSION: Because of the high prevalence of the use of
      complementary and alternative medicines and the tendency to discontinue drug
      therapy during these treatments, patients should be educated about the importance
      of pharmacological therapies.

PMID- 15456627
TI  - [Latex allergy].
AB  - Latex allergy has become an increasing cause of morbility in the last few years
      and is now recognized as an international health problem. The prevalence of latex
      sensitization among the general population is less than 1 %. The groups at
      highest risk include healthcare workers, rubber industry workers, patients with a
      history of multiple surgical procedures, particularly children with spina bifida
      and urogenital abnormalities, atopic individuals, and patients with certain fruit
      allergies (especially kiwi, avocado, chestnut and banana). The molecular and
      immunological characteristics of several natural latex allergens have been
      identified. Symptoms range from contact urticaria to anaphylaxis. Diagnosis is
      based on clinical history and is confirmed by skin prick tests. Measurement of
      serum specific IgE to latex can also be useful. The best treatment is latex
      avoidance and substitution by other materials. However, because latex products
      are ubiquitous in medical and nonmedical devices of daily use, a latex-free
      environment is not easy to achieve. In some patients, immunotherapy could be an
      alternative.

PMID- 15456628
TI  - Allergy to dexchlorpheniramine. Study of a case.
AB  - INTRODUCTION: Dexchlorpheniramine (DH) is a classical or first generation
      antihistamine belonging to the ethanolamine group. Adverse effects related to
      these antihistamines are frequent, but the hypersensitivity reactions described
      in the literature since 1940 are exceptional. We report the case of a 32-year-old
      woman who experienced two episodes of akathisia secondary to intravenous (i.v.)
      dexchlorpheniramine administration for a possible hypersensitivity reaction to
      local anesthetics. MATERIAL AND METHODS: Allergological study consisted of the
      following tests: skin prick tests with routine allergens, with a negative result;
      skin prick and intradermal tests with local anesthetics and DH, with a positive
      result to DH in the intradermal skin test (+ +); serum specific IgE, which was
      within normal levels; histamine release test with DH with a negative result, and
      the basophil activation test (BAT) with local anesthetics and DH, which was
      positive for DH and weakly positive to Lidocaine. CONCLUSION: BAT is proving to
      be a highly useful tool in the field of drug allergy, with a higher sensitivity
      and specificity than other in vitro tests. Because it avoids the need for
      provocation tests, this is especially important in drug-induced allergic
      reactions in which in vivo tests are repeatedly negative despite a clear clinical
      history.

PMID- 15456629
TI  - Cereal-induced anaphylaxis in an adult after eating a baby cereal formula.
AB  - Ingestion of infant cereal formula as a cause of anaphylaxis has been exclusively
      described in children. We report the case of a man who experienced an
      anaphylactic reaction after eating his son's cereal formula. We believe that
      cereals constitute a rising problem and a hidden allergen that can cause severe
      reactions. Although these reactions are not fully understood, they may possibly
      be a life-long event.

PMID- 15456630
TI  - Weight change and the risk of late-onset breast cancer in the original Framingham
      cohort.
AB  - OBJECTIVE: Adult weight gain has been associated with a twofold risk of
      postmenopausal breast cancer. Data are limited regarding whether weight gain at
      specific periods of marked changes in estrogen- and insulin-related hormones have
      different risk associations. This study assesses the relation of adult weight
      change overall and at specific, hormonally relevant times with diagnosis of a
      first breast cancer after age 55 (late onset). METHODS: Framingham study data
      were used to assess premenopausal (25-44 yr), perimenopausal (45-55 yr),
      postmenopausal (after 55 yr), and adult lifetime (from 25 yr) weight change in
      relation to late-onset breast cancer in 2,873 women followed for up to 48 yr,
      with 206 late-onset breast cancers. RESULTS: Adult lifetime weight gain was
      associated with an increased risk of late-onset breast cancer (P trend = 0.046).
      Weight gain during specific time periods was not associated with breast cancer.
      Data suggested a possible decreased risk of breast cancer with weight loss from
      ages 25 to 44 and 45 to 55 yr (relative risk = 0.4 [0.2-1.2] and 0.5 [0.3-0.9],
      respectively). CONCLUSION: These data confirm prior reports of an association
      between adult lifetime weight gain and increased risk of late-onset breast cancer
      and support current recommendations to avoid adult weight gain.

PMID- 15456631
TI  - Fermented milks, probiotic cultures, and colon cancer.
AB  - Colorectal cancer (CRC) is a major cause of death from cancer in the Western
      world. Approximately 70% of CRC is associated with environmental factors,
      probably mainly the diet. There is interest in the potential protective role of
      fermented milks containing probiotic cultures against CRC. This article analyzes
      the existing data from human, animal, and in vitro studies that explore whether
      consumption of milks fermented with probiotic cultures could play a role in colon
      cancer risk reduction. Cohort studies have failed to detect significant effects,
      but most case-control studies favor a protective role of fermented milks against
      colon cancer. Interventional studies have shown a shift of intermediate markers
      of CRC risk in human subjects from a high- to low-risk pattern after ingestion of
      fermented milks or probiotics. Animal studies consistently show a reduction in
      chemically induced colorectal tumor incidence and aberrant crypt formation
      accompanying probiotic administration. In vitro studies also provide evidence of
      protection, and permit a better understanding of active compounds involved, and
      of the mechanisms underlying their anticarcinogenic effects. Probiotics may
      beneficially modulate several major intestinal functions: detoxification, colonic
      fermentation, transit, and immune status, which may accompany the development of
      colon cancer. Although the evidence is not conclusive and much further research
      is required, the data reviewed constitute a promising body of evidence supporting
      the protective role of milks fermented with probiotic cultures in colon cancer
      risk reduction.

PMID- 15456632
TI  - Association of fluids from beverages with risk of rectal cancer.
AB  - Little information is available about how fluid intake from beverages and sources
      of fluid intake influence risk of rectal cancer. We examined these associations
      with risk of incident rectal cancer in a population-based case-control study of
      952 cases and 1,205 controls living in northern California and Utah. We also
      determined if intake of fiber (soluble and insoluble), physical activity, and
      nonsteroidal anti-inflammatory medications (NSAIDs) or aspirin modified the
      associations between fluid intake and rectal cancer. We identified a modest
      inverse association of water intake (odds ratio, OR = 0.70; 95% confidence
      interval, CI = 0.48, 1.02) and total fluid intake (high vs. low OR = 0.70; 95% CI
      = 0.46, 1.06) with risk of rectal cancer in men and a positive association with
      juice among women (high vs. low OR = 1.56; 95% CI = 1.00, 2.41). Risk of rectal
      cancer increased nonsignificantly among men with beer consumption, among women
      with high white wine use, and among men and women with high long-term alcohol
      use. NSAIDs modified the association of alcohol consumption with rectal cancer:
      1) risk associated with beer increased among men who did not take NSAIDs and had
      a high beer intake (OR = 1.60; 95% CI = 1.08, 2.39) and 2) risk associated with
      long-term alcohol intake increased in a linear fashion in women who did not use
      NSAIDs (OR = 1.98; 95% CI = 1.15, 3.40). Risk of rectal cancer increased among
      estrogen-negative women if they consumed any beer or white wine but decreased
      among estrogen-positive women with beer. In men, low intake of water and low
      insoluble fiber intake were associated with increased risk of rectal cancer
      beyond that of either factor alone (OR = 1.82; 95% CI = 1.11, 3.00). The
      interactions of fiber with water intake suggest that bowel motility may be the
      mechanism responsible for modification of rectal cancer risk for water.
      Associations of alcohol to risk for rectal cancer may be related to cellular
      hyperproliferation and may be modified by NSAID use.

PMID- 15456633
TI  - Fish, long-chain n-3 polyunsaturated fatty acids, and risk of colorectal cancer
      in middle-aged Japanese: the JPHC study.
AB  - Although long-chain n-3 polyunsaturated fatty acids (Ln-3 PUFA), which are
      abundant in fish, have shown protective effects on colorectal cancer in
      laboratory studies, epidemiological studies to date have not been consistent. We
      evaluated the relationship of consumption of fish and Ln-3 PUFA to the colon and
      rectal cancer risk in the two cohorts of the Japan Public Health Center-based
      prospective study of 42,525 men and 46,133 women. Dietary and other exposure data
      were obtained between 1990 and 1994. Through December 1999, 705 cases of colon
      and rectal cancer were documented. When data from the two cohorts were pooled,
      multivariable relative risks (RRs) for the highest quartile compared with the
      lowest quartile of fish consumption were 1.07 (95% confidence interval, CI = 0.77
      1.48) for colon cancer and 0.95 (95% CI = 0.63-1.43) for rectal cancer with no
      dose-risk trend. RRs for the highest quartile compared with the lowest quartile
      of eicosapentaenoic acid consumption were 1.05 (95% CI = 0.76-1.46) for colon
      cancer and 0.91 (95% CI = 0.60-1.38) for rectal cancer with no dose-risk trend.
      This study does not support the role of fish and Ln-3 PUFA in the etiology of
      colon and rectal cancer in this population whose fish consumption was high and
      the variation in Ln-3 PUFA consumption was large.

PMID- 15456634
TI  - Sex-specific differences in colon cancer associated with p53 mutations.
AB  - INTRODUCTION: Sex-specific differences in observed incidence rates, tumor
      subsite, and diet and lifestyle associations with colon cancer have been
      observed. We evaluate sex-specific associations with p53 mutations in colon
      cancer to add to understanding of these differences. Data from a large population
      based incident case-control study of colon cancer were used to evaluate age and
      gender associations with p53 mutations. To obtain a better understanding of
      gender-specific associations, we evaluated the role of estrogen as a mediator of
      risk. For these analyses, women were classified as estrogen positive or negative,
      based on menopausal status and use of hormone replacement therapy (HRT). RESULTS:
      There was a significant interaction between age and sex and risk of an acquired
      p53 mutation compared with p53 Wt. Among men, there was an increase in p53
      mutations with age, whereas among women the opposite was observed. Associations
      with parity, oral contraceptive use, and total ovulatory months were not
      associated with p53 mutations. However, recent use of HRT reduced risk of all
      tumors, as did being estrogen positive. Women who were estrogen positive (either
      premenopausal or recent users of HRT) were at a significantly increased risk of
      an acquired p53 mutation if they consumed a diet with a high sugar index (odds
      ratio = 2.94; 95% confidence interval = 1.47-5.89); similar increases in risk of
      p53 mutations were not observed for men or women who were estrogen negative.
      CONCLUSIONS: Although sex-specific associations were detected for acquired p53
      mutations, they do not indicate a unique role of estrogens in the mutation of
      p53. These data are consistent with a role for estrogen in altering
      susceptibility to diet and lifestyle factors possibly via an insulin-related
      mechanism.

PMID- 15456635
TI  - Changes in diet during adult life and risk of colorectal adenomas.
AB  - To evaluate the associations of changes in diet during adult life with adenoma
      risk, data from a case-control study of 146 colorectal adenomas and 226 controls
      were analyzed. Dietary habits during the year before sigmoidoscopy and when
      subjects were 30 yr old were collected using a food-frequency questionnaire.
      Change in frequency of consumption during adulthood was calculated by subtracting
      frequency of consumption of specific foods or food groups at age 30 yr from
      frequency of consumption during the previous year (recent consumption).
      Associations with changes in frequency of consumption were estimated by odds
      ratios (ORs) and 95% confidence intervals (CIs). There was no association for
      foods or food groups consumed at age 30 yr. For recent consumption, more frequent
      consumption of red meat, breakfast sausage, and pork chops/ham steaks and less
      frequent consumption of fish, chicken/turkey, and vegetables were related to a
      higher risk. Compared with individuals with the highest reduction in consumption
      since age 30 yr, risks were higher for those with smallest reduction in red meat
      intake (OR = 2.8; CI = 1.1-7.3), particularly for hamburgers/cheeseburgers (OR =
      2.8; CI = 1.2-6.8) and pork chops/ham steaks (OR = 3.7; CI = 1.6-8.7). In
      contrast, individuals in the highest quartile of increased consumption of fish
      (OR = 0.6; CI = 0.3-1.1) and vegetables (OR = 0.5; CI = 0.3-1.1) had a lower risk
      compared with those with minimal increase in consumption. In conclusion,
      irrespective of frequency of consumption at age 30 yr, a greater reduction in
      consumption of red meat and a larger increase in consumption of vegetables since
      age 30 yr were associated with a decreased risk of colorectal adenomas later in
      life.

PMID- 15456636
TI  - A pilot clinical study of short-term isoflavone supplements in breast cancer
      patients.
AB  - Many laboratory-based studies have shown that soy can suppress breast cancer
      proliferation. However, given the recent controversy generated by animal
      experiments that soy may under certain conditions stimulate breast cancer growth,
      we decided to carry out a pilot clinical trial in order to elucidate any
      interaction(s) between short-term isoflavone supplement administration and breast
      cancer growth. After a core-needle biopsy established the diagnosis of breast
      cancer, 17 patients were administered soy isoflavone tablets for two weeks. This
      surgically based study provided the unique opportunity to make objective
      observations based on human breast cancer tissues and blood obtained prior to and
      after isoflavone supplement treatment in the same patient. Twenty-six historical
      control cases with similar characteristics to the experimental patients were
      selected for comparison. We observed that the apoptosis/mitosis ratios in
      isoflavone-treated cancer specimens were not significantly different from those
      of control untreated cancer specimens. Furthermore, there appeared to be a
      statistically nonsignificant trend towards cancer growth inhibition in the
      isoflavone treatment group, as manifested by higher apoptosis/mitosis ratios
      compared with those from the control untreated group. Ex vivo/in vitro assays
      using serum from breast cancer patients prior to and at the conclusion of soy
      treatment reveal no significant proliferative changes on both breast cancer cells
      and endothelial cells. We concluded that the effect of soy on breast cancer
      deserves further studies in larger clinical trials.

PMID- 15456637
TI  - High dietary iron and copper and risk of colorectal cancer: a case-control study
      in Burgundy, France.
AB  - Several hypotheses have been proposed for colorectal carcinogenesis, including
      formation of free radicals. A case-control study compared nutrient intake in 171
      colorectal cancer cases versus 309 general population controls, using a detailed
      face-to-face food history questionnaire. A food composition table enabled us to
      determine the mean composition of the diet in macro- and micronutrients. Dietary
      intakes were separately categorized into quartiles by gender. Logistic regression
      models were adjusted for age, sex, energy, exercise, and body mass index. High
      energy, copper, iron, and vitamin E intakes were associated with an overall
      increased risk of colorectal cancer. The odds ratios associated with the fourth
      quartile of intake were 2.3 (95% confidence interval, 1.3-4.0), 2.4 (1.3-4.6),
      2.2 (1.1-4.7), and 1.8 (1.0-3.4) for energy, copper, iron, and vitamin E,
      respectively. There were no significant associations with dietary fiber, folate,
      calcium, or antioxidant vitamins other than vitamin E. These findings regarding
      iron and copper suggest that free radicals play an important role in colorectal
      carcinogenesis, while the findings regarding vitamin E are so far unexplained.

PMID- 15456638
TI  - Chemopreventive effect of dietary d-alpha-tocopheryl succinate supplementation on
      precancer colon aberrant crypt formation and vitamin E analogue levels in young
      and old rats.
AB  - This study examined the effects of dietary d-alpha-tocopheryl succinate (TS) in
      female rats, 20 mo (OLD) or 2 mo (YNG) of age, on azoxymethane (AOM)-induced
      colonic aberrant crypt foci (ACF) and tissue distribution of d-alpha-tocopherol
      (alphaT), d-gamma-tocopherol (gammaT), and alphaTS. Rats were fed a commercial
      rodent chow supplemented with or without 1 (YNG) or 2 (OLD) g alphaTS/kg diet for
      1 week prior to ip administration of AOM to induce colon ACF. The animals were
      sacrificed after 49 days of exposure. The results showed that OLD rats had
      significantly fewer ACF than YNG animals, and the percent body fat and serum
      triglycerides were significantly higher in the OLD group compared with the YNG.
      However, only OLD animals receiving alphaTS had significantly reduced numbers of
      larger ACF and significantly higher levels of colonic alphaT, gammaT, and
      alphaTS. These data support previous studies demonstrating that dietary alphaTS
      administration is protective against intestinal cancer. Also, this is the first
      study to show that alphaTS accumulates in most tissues following dietary
      exposure. We hypothesize that increased colon accumulation of fat-soluble vitamin
      E compounds and subsequent chemoprevention may be related to greater percent body
      fat and serum triglycerides in OLD animals receiving dietary TS.

PMID- 15456639
TI  - Chemoprevention of colorectal cancer by grape seed proanthocyanidin is
      accompanied by a decrease in proliferation and increase in apoptosis.
AB  - Effects of proanthocyanidin (PA), procyanidin B-2 (B-2), and epigallocatechin
      gallate (EGCG) on azoxymethane (AOM)-induced colonic preneoplastic aberrant crypt
      foci (ACF) formation were investigated using F344 rats. The numbers of total ACF
      in rats treated with 0.002% PA and 0.05% B-2 were significantly decreased
      compared with the AOM alone group (control). Cell proliferation in the colon, as
      shown by proliferating cells nuclear antigen (PCNA), was also reduced in those
      treatments. The single-stranded DNA (ssDNA) labeling index, a marker for
      apoptosis, was significantly increased in 0.002% PA and 0.05% B-2 groups compared
      with control. Moreover, the numbers of CD11b/c+ cells (macrophages) and NKR-P1A+
      cells (NK cells) in the all groups were significantly increased compared with
      control. In an in vitro study using rat colon cancer cell line RCN-9, PA,
      especially 5-10mer of PA (PA5/10), strong growth inhibition was shown. PA5/10
      caused the most remarkable apoptosis as cleared by FACS analysis. These cells
      showed significantly increased caspase-3 activity. The results would suggest that
      the PA, especially PA5/10, might strongly enhance caspase-3 activity and cause
      apoptosis in cancer cells. PA at fairly low doses in the long term might serve as
      an effective means for preventing colon carcinogenesis.

PMID- 15456640
TI  - Effect of red clover isoflavones on cox-2 activity in murine and human
      monocyte/macrophage cells.
AB  - Long-term use of nonsteroidal anti-inflammatory drugs is associated with a
      reduction in the incidence of a range of cancers, the mechanism of which is
      thought to be cyclooxygenase (COX) inhibition. Because long-term ingestion of
      foods rich in isoflavones, such as legumes (beans, peas, lentils) has been
      associated with reduced cancer incidence, it was considered useful to examine the
      COX-inhibitory activities of individual isoflavones. Red clover dietary
      supplements also contain varying ratios of the 4 isoflavones commonly found in
      legume-based diets, namely, daidzein, genistein, formononetin, and biochanin.
      Using 2 separate cell assays, this study examined the ability of the isoflavones
      found in red clover to inhibit COX enzyme activity in both the murine macrophage
      cell line RAW 264.7 and human monocytes. Within the range of 1-40 microM in RAW
      264.7 cells and 10-100 microM in human monocytes, isoflavones were able to reduce
      significantly the synthesis of prostaglandin E2 and/or thromboxane B2 (P < 0.001
      to P < 0.05), indicating COX inhibition. Thus, it is possible that the lower
      rates of some cancers in populations with a high intake of dietary isoflavones is
      linked to their inhibition of COX activity.

PMID- 15456641
TI  - Inhibition of the rat breast cytosolic bioactivation of ethanol to acetaldehyde
      by some plant polyphenols and folic acid.
AB  - There is a well-established association between alcohol consumption and breast
      cancer risk. About 4% of the breast cancers in developed countries are estimated
      to be attributable to drinking alcohol. The mechanism of tumor promotion by
      alcohol remains unknown. Recent studies from our laboratory and others showed the
      ability of mammary tissue to bioactivate ethanol to mutagenic/carcinogenic
      acetaldehyde and free radicals. Xanthine oxidoreductase (XOR) is an enzyme
      involved in those biotransformation processes. In the present study, we provide
      evidence of the ability of different natural polyphenols and of folic acid
      derivatives to inhibit the biotransformation of alcohol to acetaldehyde by rat
      breast cytosolic XOR. Folic acid and dihydrofolic acid, at concentrations of 10
      microM, inhibited 100% and 84%, respectively, of the cytosolic acetaldehyde
      formation. Thirty-five polyphenols were tested in these initial experiments:
      ellagic acid, myricetin, quercetin, luteolin, and apigenin inhibited 79-95% at 10
      microM concentrations. The remaining polyphenols were either less potent or
      noninhibitory of acetaldehyde formation at similar concentrations in these
      screening tests. Results are relevant to the known preventive effects of folic
      acid against alcohol-induced breast cancer and to their potential preventive
      actions if added to foods or alcoholic beverages.

PMID- 15456642
TI  - Conjugated linoleic acid inhibits proliferation and modulates protein kinase C
      isoforms in human prostate cancer cells.
AB  - Prostate cancer is the second most common cancer in men. The disease etiology is
      poorly understood, but diet and lifestyle are contributory factors. Conjugated
      linoleic acids (CLAs), naturally occurring fatty acids in ruminant food products,
      have antitumor properties in animal models of cancer and antiproliferative
      effects on cancer cells in vitro. The cellular mechanisms by which CLAs elicit
      these effects are unclear, particularly for prostate cancer cells. We have
      previously identified protein kinase C (PKC) isoforms, alpha, delta, iota, mu,
      and zeta in LNCaP prostate cancer cells. The objective of this study was to
      determine the effects of CLAs (individual cis-9, trans-11 and trans-10, cis-12
      isoforms and a 50:50 mixture) on PKC isoform abundance in LNCaP cells. Confluent
      cells were treated with 6, 25, and 50 microM CLA for 0.5, 6, and 24 h. Cytosol
      and membrane protein fractions were assayed for PKC isoforms (mainly alpha and
      delta but also iota, mu, and zeta) by Western blot analysis using specific
      antibodies. CLAs clearly modulated the abundance of these PKC isoforms, both
      positively and negatively, depending on the isoform, concentration of CLAs, and
      period of treatment. Increased PKC-delta and decreased PKC-iota membrane
      abundance was consistent with CLAs eliciting increased apoptosis and, in part,
      with their antitumor effects.

PMID- 15456644
TI  - Personality assessment without borders: adaptation of the MMPI-2 across cultures.
AB  - In contemporary psychology, personality assessment knows few national or cultural
      boundaries. Psychological tests developed in one country are often translated and
      adapted into cultures that might appear to be greatly different from the country
      of origin. In this article, I address the factors that are important to
      international test adaptation and examine problems that can adversely affect
      cross-cultural test research programs. I address qualities important for
      verifying the accuracy and adequacy of cross-cultural assessment. I review the
      extensive adaptation of the MMPI (Hathaway & McKinley, 1940) and MMPI-2 (Butcher,
      Dahlstrom, Graham, Tellegen, & Kaemmer, 1989), the most frequently used
      personality measure. I highlight several contemporary research trends in
      international personality assessment.

PMID- 15456645
TI  - Chance and choice, change and continuity--that's life.
AB  - Responding to this invitation to write an autobiography, I have tried to put in
      some order, the jumble of memories that come to mind. There are markers of the
      journey--the major decisions and changes in direction, many influenced by
      external events. Despite turns and detours, there is also continuity of interests
      and behavioral style. My beginnings on a Nebraska farm were a considerable
      distance in place and character from my current retirement in Oregon. The trail
      of events was especially marked by the death of my father, early choice of
      psychology, military service in Germany, marriage in Paris, establishing the
      university clinic and clinical program at the University of Oregon, starting a
      school of Community Service and Public Affairs, working with Leona Tyler on books
      and an extensive research project, and a year going around the world with my
      family including a long period in India. My principal contributions to
      personality assessment include cross-cultural studies, development of a boredom
      scale, community psychology connections, many reviews, books in clinical
      psychology and assessment, and work with students and others who continue this
      important branch of psychology.

PMID- 15456646
TI  - Personality in proportion: a bipolar proportional scale for personality
      assessments and its consequences for trait structure.
AB  - Trait structures resulting from personality assessments on Likert scales are
      affected by the additive and multiplicative transformations implied in interval
      scaling and correlational analysis. The effect comes into view on selecting a
      plausible alternative scale. To this end, we propose a bipolar bounded scale
      ranging from -1 to +1 representing an underlying process in which the assessor
      would review and discount positive and negative behavioral instances of a trait.
      As an appropriate index of likeness between variables X and Y, we propose LXY =
      SigmaXY/N, the average of the raw scores cross products. Using this index, we
      carried out a raw scores principal component analysis on data consisting of 133
      participants who had each been rated by 5 assessors including self on 914 items.
      Contrary to the Big-Five structure that was found in these data on standard
      analysis, the results showed a relatively large first principal component F1 and
      2 very small ones, F2 and F3. The sizes LFF=SigmaF2/N, the averages of the
      squared component scores, were modest to small. It thus appears that the scale,
      bipolar proportional versus standard, has a profound impact on the size and
      structure of personality assessments. The dissimilarity remains on analyzing self
      ratings rather than averaged (over the 5 assessors) ratings.

PMID- 15456647
TI  - The making of meaning: comments on Hofstee and Ten Berge.
AB  - Hofstee and Ten Berge (2004/this issue) outline a method of scale transformation
      that places scores on a common absolute scale. This contrasts with traditional
      relative methods of transformation, which involve scaling in relation to a sample
      mean. Their primary intention seems to be to produce a scale that is
      intrinsically meaningful. This issue of scale meaning is discussed in some
      detail, including reference to an alternate approach to absolute scaling offered
      by Cohen, Cohen, Aiken, and West (1999). Ultimately, neither approach to absolute
      scaling seems completely satisfactory as a resolution to this problem. It is
      suggested that the lack of meaning inherent to many psychosocial measures is a
      natural product of traditional aggregative practices in scale development and may
      be invulnerable to statistical correction.

PMID- 15456648
TI  - Personality out of proportion?
AB  - The field of personality assessment has evolved the normative practice of
      centering scores on their means, evaluating associations among measures with
      Pearson correlations, and using factor analytic methods to reduce redundancy and
      provide putative explanatory variables. At least some of these explanatory
      variables, or factors, have become well-known elements in trait theories of
      personality structure (e.g., the Five-factor model). Hofstee and Ten Berge
      (2004/this issue) suggest an alternative set of procedures arising from treating
      the midpoints of bipolar rating scales as true zero points. These procedures lead
      to a very different view of personality structure in which one factor provides a
      nearly sufficient summary of personality judgments. I scrutinize the
      methodological choices implied by these procedures here. This evaluation leads to
      the conclusion that Hofstee and Ten Berge provide methods and results that cannot
      serve to replace normative practice and well-known findings but do provide
      insight into important questions not typically addressed by personality
      assessors.

PMID- 15456650
TI  - A consideration of challenges to psychological assessment instruments used in
      forensic settings: Rorschach as exemplar.
AB  - In this brief primer, we provide an outline of key issues that will help
      psychologists organize and prepare their expert testimony. These issues include
      the need to obtain essential sources of research, a review of the actual legal
      standards regarding admissibility of test data in expert testimony, the nature of
      the expert relative to the assessment instrument in expert testimony, the nature
      of legal versus scientific debate, and the examination of appropriate
      qualifications of expertise when offering legal testimony. In addition, we use a
      summary of information contained in several recent articles to address challenges
      directed against forensic psychological testing. We use the empirical literature
      on the Rorschach as an exemplar in discussing these issues, as the admissibility
      of the Rorschach in particular has been challenged, and the issues frequently
      focused on with the Rorschach are equally applicable to other psychological
      measures. In this article, we provide essential sources of Rorschach research
      regarding several empirical studies that summarize important information and
      directly address previous criticisms of the measure.

PMID- 15456651
TI  - Investigating invariance in the factorial structure of the anxiety sensitivity
      index across adult men and women.
AB  - The Anxiety Sensitivity Index (ASI; Peterson & Reiss, 1992) is one of the most
      widely used measures of the fear of anxiety-related sensations. Important gender
      differences also seem to exist in that women report higher levels of anxiety
      sensitivity than men. The primary objective of this study was to determine
      whether an equivalent factorial structure exists for the ASI among nonclinical
      adult men and women. In Study 1 (568 women; 251 men), the 2-factor (Fear of
      Cardiopulmonary Sensations and Fear of Mental Catastrophe), 10-item version of
      the ASI reported by Schmidt and Joiner (2002) provided the best fit to the data
      for both men and women. Using this model, Study 2 (503 women, 255 men) examined
      whether the factorial structure of the 10-item ASI was invariant for men and
      women. Noninvariance was found for one item on the Fear of Mental Catastrophe
      subscale (Item 15="When I am nervous, I worry that I might be mentally ill"). The
      implications of this are that this item should be dropped if an equivalent factor
      structure is to be assumed between men and women.

PMID- 15456652
TI  - A psychometric evaluation of the Harvey Imposter Phenomenon Scale.
AB  - In this article, we present psychometric properties on the 14-item Harvey
      Imposter Phenomenon (IP) Scale (Harvey, 1981) among a sample of U.S. adolescents
      (N = 136). Item analyses, internal consistency reliability, and principal
      components analysis (PCA) were computed to assess the reliability and factor
      structure of the IP scores. Although the internal consistency reliability (e.g.,
      Cronbach's alpha) was reasonably acceptable (alpha =.70), the item analyses and
      subsequent PCA suggest concern for the content homogeneity and factor structure
      of composite scores obtained from the 14-item measure. The results of this study
      suggest that the indiscriminate use of the Harvey IP Scale is cautioned relative
      to the insufficient psychometric properties.

PMID- 15456653
TI  - A longitudinal SEM approach to STAI data:two comprehensive multitrait-multistate
      models.
AB  - I investigated psychometric properties of data gathered with the State-Trait
      Anxiety Inventory (STAI; Spielberger, Gorsuch, Lushene, Vagg, & Jacobs, 1983,
      1993) using structural equation modeling. Two features were integrated into the
      modeling: Bistability refers to the duality that is raised once the wording
      effect is recognized, and second-order, state-residual/trait decomposition refers
      to the basic bidimensionality of the data, which is revealed in a longitudinal
      perspective. I tested the approach on 2 samples of French adults (total N = 888)
      borrowed from Vautier and Jmel (2003). The models provided acceptable goodness of
      fit and supported the empirical need for hypothesizing 2 trait factors and 4
      transient sources of true variance. I assessed the multidimensional composition
      of the composites using reliability analyses. I discuss theoretical consequences
      of the approach.

PMID- 15456658
TI  - Competencies are all the rage in education.

PMID- 15456660
TI  - What's new in cancer education research.

PMID- 15456662
TI  - Development of required postgraduate palliative care training for internal
      medicine residents and medical oncology fellows.
AB  - BACKGROUND: The need for better care for terminally ill patients led us to create
      an educational program to provide internal medicine residents and medical
      oncology fellows basic competency in palliative and end-of-life care. METHODS: An
      interdisciplinary team identified educational strategies, course objectives,
      content, and evaluation instruments. RESULTS AND CONCLUSIONS: Our strategy is to
      use a required Web-based course to establish a knowledge base upon which specific
      training during clinical rotations build skills. Field testing of the Web course
      showed it was an effective tool for delivering clinically applicable content.
      Skill building experiences are now being integrated into selected clinical
      rotations.

PMID- 15456663
TI  - Fellows' forum: a workshop on the stresses of being an oncologist.
AB  - BACKGROUND: A pilot workshop was designed for medical oncology fellows to discuss
      the personal dimension and stresses of clinical oncology training. METHODS: Focus
      was directed at increasing awareness not only of the patients' psychosocial needs
      but also the fellows' personal responses to them. Fellows were invited to a
      bimonthly luncheon to discuss difficult cases they had encountered from a
      psychosocial perspective. The sessions were cofacilitated by Medical Oncology and
      Psychiatry. RESULTS: Recurrent topics included the stresses of breaking bad news,
      treating pain, managing the depressed or angry patient, problems related to end
      of life, and complex family and cultural issues. CONCLUSIONS: There was high
      satisfaction expressed with the forum.

PMID- 15456664
TI  - An analysis of the American Cancer Society Clinical Research Training program.
AB  - BACKGROUND: In 1996 the American Cancer Society initiated a Clinical Research
      Training Grant for junior investigators. This was a 3-year mentored grant for
      preclinical and clinical research training. Two hundred four individuals applied
      from 103 institutions, and 25% were funded. METHODS: This report is an initial
      assessment of the impact of the program on future career development. Both the
      funded and unfunded groups were queried regarding prior research experience,
      publications, and academic status. RESULTS AND CONCLUSIONS: Although small
      differences were seen between the funded and unfunded groups, the major finding
      was that those applicants with prior research and publication experience were
      more likely to get funded, but both groups were highly motivated to seek an
      academic career.

PMID- 15456665
TI  - Colon cancer risk counseling by health-care providers: perceived barriers and
      response to an internet-based cancer risk appraisal instrument.
AB  - BACKGROUND: Risk appraisal instruments may be helpful in reinforcing prevention
      messages, although little is known about physician acceptance of such
      instruments. OBJECTIVE: We explored perceived barriers to colon cancer risk
      counseling and responses to the colon cancer component of an Internet-based risk
      appraisal instrument. METHODS: We qualitatively assessed provider perceptions of
      barriers to colon cancer prevention and screening, and their responses to the
      Harvard Cancer Risk Index using focus groups of primary care providers. RESULTS:
      Many providers commented that the risk appraisal instrument may be most helpful
      to reinforce messages by a health-care provider. The tool may increase awareness
      about modifiable risk factors for cancer and help patients prioritize changes as
      well as improve screening acceptance. With regard to barriers to counseling
      patients about colon cancer prevention and screening, providers expressed
      concerns that behaviors are too difficult to change. In addition, they were
      frustrated by limited time for prevention counseling and poor reimbursement.
      CONCLUSIONS: The Internet-based risk index was well accepted, although providers
      thought it would be most effective when used to complement provider messages
      about prevention. Use of an Internet-based risk index along with physician
      counseling could help improve cancer prevention practices and cancer screening
      acceptance.

PMID- 15456666
TI  - Video breast health kits: testing a cancer education innovation in older high
      risk populations.
AB  - BACKGROUND: The Breast Health Kit for Women Over 60 project was a 3-year study
      funded by NCI to develop and field test video self-instruction programs designed
      to increase breast cancer screening for older black and white women. METHODS:
      Impact of kit use on knowledge about breast cancer risk/screening, breast self
      examination (BSE) proficiency, and mammography use was assessed with 439 women in
      Massachusetts and Georgia. BSE proficiency was measured by demonstration of
      inspection/palpation skills and detection of lumps in a simulation model.
      Analysis with a noncompliant mammography user subsample (N = 143) tested the
      effectiveness of kit use on mammography screening. The sample was predominantly
      black (76%) with mean age of 71.6 years and mean education of 10.6 years.
      RESULTS: Analyses of covariance revealed that women who used the kits had
      significantly better knowledge about breast cancer risk/screening (F = 23.6, P <
      or =.001) and were more proficient at BSE than kit nonusers as measured by both
      skills (F = 47.9, P < or =.001) and detection of lumps (F = 36.8, P < or =.001).
      No significant differences were found between subsample groups in receiving a
      poststudy mammogram, but a trend toward having mammograms was noted in the
      subsample who used the kits (chi(2) = 1.7, P < =.09). CONCLUSIONS: Age and
      ethnically sensitive self-instructional breast health kits were found to be
      effective in increasing knowledge about breast cancer risk and BSE proficiency in
      older women. Future research is needed to explore how other strategies combined
      with kit use can assure mammography compliance in this population.

PMID- 15456667
TI  - Cancer education and cancer prevention education for K-12 students and teachers.
AB  - BACKGROUND: A health science educational outreach program which began in 1991 and
      targets K-12 teachers and students has had 15,911 participants consume 60,069
      hours of education as of the end of December 2003. The program is called the
      "Partners in Health Sciences" (PIHS) program. Many educational activities in the
      PIHS program contain information on both cancer biology and cancer prevention.
      METHODS: All of the cancer-related education offered and consumed in the history
      of the PIHS program was identified and quantified. RESULTS: In the PIHS program
      984 K-12 teachers and 2,376 grade 7-12 students consumed 4,477 and 3,029 hours of
      cancer-related education, respectively. CONCLUSIONS: Cancer education encompasses
      much more than cancer prevention education and includes different aspects of
      cancer biology from the cell to the organism levels of biological organization.
      Selected topics in cancer biology can be used to motivate K-12 teachers and
      students to learn more about basic normal biology while simultaneously learning
      about cancer. In addition, the psychosocial impact of cancer on the individual,
      the family, and the community can be used to foster K-12 student interest in
      studying behavioral science.

PMID- 15456668
TI  - Cancer risk factor assessment among Chamorro men in San Diego.
AB  - BACKGROUND: Little is known about the health of Chamorros residing in the United
      States. METHOD: The CDC's Behavioral Risk Factor Surveillance System was used to
      assess cancer-related behavioral risk factors in San Diego's Chamorro men, and
      the Chamorro Directory International was used to recruit them. RESULTS: Of the
      100 Chamorro men, 19% smoked, 38.4% reported eating 5 or more fruits and
      vegetables daily, 48.8% reported being current on their prostate cancer
      screening, and 74.4% reported being current on their colorectal cancer screening.
      CONCLUSIONS: This sample of Chamorro men reported higher rates of health
      promoting practices than nationwide averages.

PMID- 15456669
TI  - Readability of cancer information on the internet.
AB  - BACKGROUND: Literacy is considered an essential component of individuals' ability
      to increase control over their health. However, the majority of printed cancer
      information is written at readability levels of high school or higher and may be
      difficult to comprehend by people who are searching for medical information.
      Since low literacy is associated with poorer health and since a growing number of
      people are searching the Internet for health information, our research questions
      were twofold: (1) What is the readability level of popular Web sites on breast,
      colon, and prostate cancers? and (2) Does readability level differ as a function
      of the Web sites' organizational origin? METHODS: Breast, colon, and prostate
      cancer Web sites were selected for analysis by comparing the first 100 hits of 10
      popular search engines. A total of 55 Web sites on breast (n = 20), colorectal (n
      = 18), and prostate (n = 17) cancers were included in the final analysis and
      assessed for readability using SMOG, Flesch-Kincaid (F-K), and Flesch Reading
      Ease (FRE) measures. RESULTS: The overall mean reading level of the cancer Web
      sites was Grade 13.7 using the SMOG formula and Grade 10.9 according to F-K. The
      mean FRE score was 41.6. The majority of Web sites (63.6%) were written at
      college level (Grade 13+) according to SMOG, especially those with a domain of
      ".com" and "org." Breast cancer sites were written at easier reading grade levels
      than sites on prostate cancer and colorectal cancer. Breast cancer sites also
      showed the largest increase in reading difficulty between opening and concluding
      paragraphs of text. CONCLUSIONS: Readability of cancer information on the
      Internet is at a college level. Individuals with basic literacy skills must be
      considered when posting cancer information on the Internet. Otherwise this
      information will remain inaccessible to a segment of the population who is at
      risk for cancer.

PMID- 15456670
TI  - Connecting rural African American and Hispanic women to cancer education and
      screening: the Avon Health Connector project.
AB  - BACKGROUND: Many barriers prevent minority women in rural areas from being
      screened for breast and cervical cancer. METHODS: A partnership was formed to
      screen low-income women in a Southern Appalachian area, with particular focus on
      African American and Hispanic populations. A lay health advisor model was
      utilized, and 45 LHAs were trained to participate in the program. RESULTS: In
      this program, 456 women were screened for breast and cervical cancer, 1943
      received health education, and 59 health professions students participated.
      CONCLUSION: A successful partnership model builds on the strengths and assets of
      partners, provides culturally competent services, and benefits from continual
      project evaluation.

PMID- 15456671
TI  - Cycles, papers, and education.

PMID- 15456674
TI  - Blood pressure reactivity can be reduced by a cognitive behavioral stress
      management program.
AB  - Although enhanced cardiovascular reactivity is extensively discussed as a
      relevant negative factor in the alteration of vascular structure, only a few
      controlled studies have been published presenting approaches to alter reactivity.
      Therefore, we examined whether enhanced reactivity could be reduced by stress
      management training (SMT). To control for expectation effects, progressive
      muscular relaxation (PMR) was the control condition. Forty-four patients with a
      blood pressure response greater than 15 mm Hg to a mental stress test
      participated in this study. Participants who took part in SMT showed a
      significantly stronger reduction of diastolic blood pressure reactivity to a
      mental stress test from pretest to posttest than the controls. Furthermore,
      patients who took part in SMT showed significantly smaller systolic blood
      pressure reactions to mental arithmetic and 2 social stress tests than the
      controls after the trainings. This study indicates that enhanced blood pressure
      reactivity can be reduced by SMT.

PMID- 15456675
TI  - Psychophysiological responses to anger provocation among Asian Indian and White
      men.
AB  - To examine cultural differences in response to anger provocation, affective,
      cognitive, behavioral, and cardiovascular responses to social confrontation, role
      plays were measured in 20 Indian male immigrants in the United States and 40
      White men. Participants engaged in 2 interactions with a nonacquiescent male
      confederate and were instructed to suppress or express their anger in
      counterbalanced order. Following each role play, participants state anger, and
      resentful and reflective cognitions pertaining to anger were assessed.
      Participants' videotaped behavioral responses were assessed for problem-solving
      skills and negative and positive verbal and nonverbal behaviors. Blood pressure
      and heart rate (HR) responses were recorded throughout the session. Results
      revealed that Indian participants used more introspective strategies comprising
      of repression and rational coping self-statements to anger provocation than their
      White counterparts. White participants experienced significantly higher HR
      responses and showed more awareness of physiological sensation compared to the
      Indian participants, but only when asked to exhibit their anger. Indian
      participants had a faster diastolic blood pressure (DBP) recovery when allowed to
      engage in anger inhibition (which is a culturally determined mode of functioning)
      compared to when they had to exhibit anger before inhibiting it. White men showed
      a heightened cardiac response to anger expression, something not seen among
      Indian men. Indian men, in contrast, exhibited delayed DBP recovery from anger
      expression and increased introspective cognitive strategies when asked to engage
      in anger exhibition, a behavior not congruent with their culture of origin.

PMID- 15456676
TI  - Depressive symptoms and cardiovascular reactivity to laboratory behavioral
      stress.
AB  - Although a growing literature associates depressive symptoms with cardiovascular
      disease (CVD), the mechanisms underlying this association have not been clearly
      determined. The cardiovascular reactivity (CVR) hypothesis suggests that
      chronically elevated CVR during psychological distress can confer disease risk
      via vascular alterations. This investigation is a quantitative review of studies
      that evaluated the association of depressive symptoms with CVR. A total of 60
      hypotheses were tested: 21 tests involved systolic blood pressure (SBP), 21
      involved diastolic blood pressure (DBP), and 18 involved heart rate (HR). The
      aggregate effect size for the relation between depressive symptoms and HR
      reactivity was moderate (d = 0.37); aggregate effect sizes were small for SBP
      reactivity (d = 0.13) and DBP reactivity (d = 0.17). Effect sizes involving SBP
      reactivity were homogenous, whereas effect sizes involving DBP and HR reactivity
      were higher for studies that examined participants with CVD. These findings
      provide partial support for the associations of depressive symptoms with CVR.

PMID- 15456677
TI  - Validation of the Detroit Area Study Discrimination Scale in a community sample
      of older African American adults: the Pittsburgh healthy heart project.
AB  - This study examined the construct validity of the Detroit Area Study
      Discrimination Questionnaire (DAS-DQ) in 49 healthy African American adults, with
      respect to its association with global measures and daily experiences of
      psychological demand. Daily experiences of psychological demand were obtained
      using ecological momentary assessment (EMA) methods. Everyday Mistreatment, as
      measured by the DAS-DQ, was significantly related to global reports of perceived
      stress and depression but was unrelated to measures of hostility and social
      desirability. Everyday Mistreatment was significantly related to average EMA
      score measures of Negative Affect and Social Conflict but was unrelated to daily
      experiences of Task Demand or Decisional Control. Negative Affect mediated the
      relation between Everyday Mistreatment and global reports of perceived stress. In
      contrast, Lifetime History of Discrimination, as measured by the DAS-DQ, was
      unrelated to global measures or daily experiences of stress. Thus, this study
      lends support to the construct validity of the DAS-DQ.

PMID- 15456678
TI  - Change in breast self-examination behavior: effects of intervention on enhancing
      self-efficacy.
AB  - This study evaluated a breast self-examination intervention to increase phase
      specific self-efficacy and positive outcome expectancies. The role of social
      cognitive predictors in the process of behavior change was investigated. Using
      cluster randomization, participants were assigned to an intervention (n = 244) or
      to a control (n = 173) group. Controls were measured twice, with 13 weeks between
      the assessments. Respondents from the intervention group received the
      intervention before the 1st measurement. The increase in the number of self
      examination components was significantly higher in the intervention group than
      among controls. Women who had never performed self-examinations before the
      intervention, as well as those who did it irregularly or incompletely, changed
      their behavior significantly. Results of structural equation modeling for a 2
      group model showed that phase-specific self-efficacy was a significant predictor
      of intention, planning, and behavior change in the intervention group. In the
      control group, these relations were weaker or remained nonsignificant. Social
      cognitive variables measured in this study explained 15% of variance of behavior
      change in the control group and 29% of breast self-examination change in the
      intervention group.

PMID- 15456679
TI  - The influences of psychosocial aspects and anxiety symptoms on quality of life of
      patients with arrhythmia: investigation in paroxysmal atrial fibrillation.
AB  - The purpose of this study was to investigate the feature of the psychosocial
      aspects of patients with atrial fibrillation and to explore the influences of the
      subjective symptoms of attack, perceived psychosocial inducers of attack, and
      anxiety on the quality of life (QOL). The participants were 240 patients with
      paroxysmal atrial fibrillation (57.89 +/- 13.78 years old), who were requested to
      complete questionnaires on the subjective symptoms of attack, perceived
      psychosocial inducers of attack, anxiety symptoms, and QOL. The results of this
      study showed that 29.5% patients met the criteria of agoraphobia of Diagnostic
      and Statistical Manual of Mental Disorders (4th ed. [DSM-IV]; American
      Psychiatric Association, 1994). This percentage of prevalence was higher than the
      general prevalence of DSM-IV data. The subjective symptoms of attack (frequency,
      duration, and distress of attack) intensify their fear of attack and agoraphobic
      symptoms, which worsen their QOL. Psychological stress is the main perceived
      inducer in daily life, and a attack induced by psychological stress affects their
      anxiety symptoms and QOL.

PMID- 15456680
TI  - Attributional style and symptoms of depression in persons with multiple
      sclerosis.
AB  - This study was designed to assess hypotheses derived from the hopelessness theory
      of depression (Abramson, Metalsky, & Alloy, 1989), specifically that negative
      attributional style would be associated with depressive symptoms and that
      negative life events would interact with negative attributional style to explain
      depressive symptoms in a sample of persons with multiple sclerosis (MS). The
      research was cross sectional in design. Data was collected via survey from 495
      persons with MS. Attributional style was positively associated with depressive
      symptoms across the whole sample. The proposition that negative life events would
      interact with negative attributional style to explain depressive symptoms was
      also supported, although only for global attributional style. Longitudinal
      studies would assist in determining the causal direction proposed by the
      hopelessness theory of depression in this population. It is also appropriate that
      clinicians consider attributional style in persons with MS whom they are treating
      for depression.

PMID- 15456681
TI  - Differential heart rate reactivity and recovery after psychosocial stress (TSST)
      in healthy children, younger adults, and elderly adults: the impact of age and
      gender.
AB  - In addition to numerous reports about psychophysiological stress responses to
      acute stressors, there are few data available on gender differences of stress
      induced heart rate responses in multiple age groups applying the same
      psychological stressor. Second, the assessment of poststress recovery appears to
      be neglected in the empirical literature. For this study, data from 5 independent
      studies were reanalyzed to investigate the impact of age and gender on heart rate
      responses and poststress recovery to a standardized psychosocial stress task
      (Trier Social Stress Test; TSST) in 28 children, 34 younger adults, and 26 older
      adults. As expected, prestressor baselines correlated significantly with
      chronological age (r = -.27, p =.01). There was a marked age-related decrease in
      the heart rate stress response (p =.0003) with children and younger adults
      showing significantly higher increases than elderly persons. The analysis of
      gender effects showed that girls had higher heart rate increases during the
      stress exposure than boys (p =.03). In younger adults, stress responsivity was
      also higher in women (p =.03). Peak heart rate responses were comparable in older
      men and women, with only men returning to prestressor baselines during the
      observation period. In sum, this reanalysis revealed differential heart rate
      responses and recovery after exposition to the TSST in healthy children, younger
      adults, and elderly adults.

PMID- 15456682
TI  - Are subjective health complaints a result of modern civilization?
AB  - Subjective health complaints without or with minimal somatic findings (pain,
      fatigue) are common and frequent reasons for encounter with the general
      practitioner and for long-term sickness leave and disability. The complaints are
      often attributed to the stressors of modern life. Is this true? We interviewed
      120 Aborigine Mangyans (native population, M age = 33.5 years, 72.5% women)
      living under primitive conditions in the jungle of Mindoro, an island in the
      Philippines, and 101 persons living in a small coastal town on the same island
      (coastal population, M age = 33.8 years, 60.4% women). Both groups had more
      musculoskeletal complaints, fatigue, mood changes, and gastrointestinal
      complaints than a representative sample from the Norwegian population (N =
      1,243). Our common subjective health complaints, therefore, are not specific for
      industrialized societies.

PMID- 15456683
TI  - Reliability and validity of functional neuroimaging techniques for identifying
      language-critical areas in children and adults.
AB  - Advances in neuroimaging technologies over the last 15 years have prompted their
      relatively widespread use in the study of brain mechanisms supporting language
      function in children and adults. We reviewed reliability and external validity
      studies of 3 of the most common functional imaging methods, functional magnetic
      resonance imaging (fMRI), magnetoencephalography (MEG), and positron emission
      tomography (PET). Although reliability and validity reports for fMRI are
      generally quite favorable, significant variability was found across studies with
      respect to methodology, preventing in some cases either the assessment of the
      reliability of individual datasets, or cross-study comparisons. Reliability and
      validity reports of MEG are strong, yet methodological questions regarding
      optimal modeling techniques remain. PET investigators report good concordance of
      language maps with data from more invasive brain mapping techniques, but its use
      of radioactive tracers and poorer spatial and temporal resolution make it the
      least optimal of the 3 methods for language mapping. Investigations of the
      cortical networks supporting language function during development and into
      adulthood should be viewed in the context of the validity and reliability of the
      methods used, with careful attention to details regarding the methodologies
      employed in the acquisition and analysis of statistical maps.

PMID- 15456684
TI  - Examination of verbal memory and recall time in children with attention deficit
      hyperactivity disorder.
AB  - In this study 22 7- to 11-year-old children diagnosed with attention deficit
      hyperactivity disorder (ADHD) and 44 age-matched controls recruited from the same
      classrooms were given a 4-item delayed serial recall task using numbers or
      phrases. Although both groups showed similar recall accuracy rates, ADHD children
      required significantly longer times to retrieve and articulate their answers than
      children from the control group, regardless of age. The findings are discussed in
      relation to theories of executive function deficits in ADHD.

PMID- 15456685
TI  - Executive functions in children aged 6 to 13: a dimensional and developmental
      study.
AB  - A cross-sectional study using 92 children aged 6 to 13 years investigated the
      dimensionality and the development of executive functioning. The measures were
      drawn from developmentally relevant conceptualizations of executive functioning
      and included a go/no-go task, a verbal fluency task, a continuous performance
      task, a Stroop-like task, a hand movements task, and a digit span task. Analyses
      revealed 3 dimensions interpreted as Disinhibition, Speed/arousal, and Working
      memory/Fluency. Age and sex differences were analyzed for the delineated
      functions, which means that the results may be taken to represent age effects at
      the level of specific processes within the executive domain rather than on single
      tests. Age-dependent changes in children's performance on all 3 dimensions were
      demonstrated, with 3 particularly active stages of maturation: early childhood (6
      8 years of age), middle childhood (9-12 years of age), and during early
      adolescence. Sex differences were only found for the speed/arousal dimension. The
      results are discussed in terms of 2 developmental executive function frameworks
      (Barkley, 1997b; Roberts & Pennington, 1996), where inhibition and the
      interaction between inhibition and working memory, respectively, are seen as key
      in the development of executive functioning.

PMID- 15456686
TI  - An investigation of impulsivity in children with early-treated congenital
      hypothyroidism.
AB  - The main feature of congenital hypothyroidism (CH) is a total or partial absence
      of thyroid hormone, caused by a developmental disorder of the thyroid gland.
      Introduction of neonatal thyroid screening allows early treatment with
      replacement hormone. As a result the prognosis of CH has greatly improved but
      neuropsychological problems do still occur. Claims that early-treated CH is
      associated with impulsivity were tested with a memory search task comprising 2
      response probability conditions: a baseline condition in which "yes" and "no"
      responses were equally probable and a response bias condition in which the
      probability of a "no" response was raised to 70%. Impulsivity was defined as the
      ability to stop and change a response set and was assessed from the amount of
      inaccurate "no" responses made. Comparisons were made between 47 children with
      early-treated CH and 35 controls at the age of 7.5 years. Children with early
      treated CH were notably slow and variable in their overall task performance but,
      most important, did not show signs of poor impulse control. Suggested short-term
      memory problems in these children could not be confirmed. Performance could not
      be attributed to early disease-related factors or lowered intelligence.

PMID- 15456687
TI  - Networks of attention in children with the 22q11 deletion syndrome.
AB  - The 22q11 chromosomal deletion syndrome (22q11 DS) is associated with learning
      disabilities and a complex neuropsychological profile. Previous findings have
      suggested that executive attention deficits might underlie other neurocognitive
      anomalies. We administered the child Attention Network Test (ANT) to 52 children
      ages 5.0 to 11.5, 32 22q11 DS children (19 girls) and 20 controls (13 girls) and
      assessed the efficiency of segregated executive, orienting, and alerting
      networks. We hypothesized that 22q11 DS children have impaired executive network
      efficiency as compared to control siblings. The internal validity of the child
      ANT was confirmed for this population. Analysis of variance results showed
      significant main effects for flanker and cue types and no interaction effect in
      either 22q11 DS children or control siblings. Compared to control siblings, 22q11
      DS children had significantly larger (less efficient) executive network scores,
      significantly increased errors on only incongruent trials, and a significant
      correlation between executive network scores and accuracy. The implications of
      these findings for future neurocognitive studies of 22q11 DS children are
      considered.

PMID- 15456688
TI  - Research on attention deficit hyperactivity disorder using the covert orienting
      paradigm of Posner.
AB  - Posner's covert orienting of attention paradigm has been used in many studies in
      the cognitive neuroscience literature to study attention. We found 9 studies in
      which it was used to study attention deficit hyperactivity disorder, but findings
      were not consistent. We present a tutorial about the paradigm's methodology and
      then review the studies. It emerges that much of the inconsistency evident can be
      attributed to procedural variations. We conclude that across the 9 studies, 2
      variables-overall slowing and right hemisphere dysfunction-differentiated
      attention-disordered persons from controls. We then offer a set of guidelines,
      which should help facilitate realization of the paradigm's promise in generating
      profiles representing different syndromes within the general classification of
      attention disorders.

PMID- 15456689
TI  - Verbal and nonverbal fluency in Spanish-speaking children.
AB  - Fluency measures are commonly used in clinical developmental neuropsychology to
      assess executive functions. Little is known about the effect of age on
      performance in these tests. This article analyzes the effect of age on measures
      of verbal (semantic and phonologic) and nonverbal (semantic and nonsemantic)
      fluency in 171 children (81 boys, 90 girls) between ages 6 and 15. Participants
      were selected from public and private schools in Guadalajara and Tijuana, Mexico.
      A significant age effect was found on all tests but no interaction between age
      and type of test was found. Significant correlations among the 4 fluency tasks
      ranged from.36 to.46. Results are consistent with the findings of normative
      studies carried out in other countries and support the cross-language validity of
      verbal fluency tests.

PMID- 15456690
TI  - Combined therapy: what does acamprosate and naltrexone combination tell us?
AB  - AIMS: Relapse prevention treatment with both acamprosate and naltrexone has been
      shown to be efficacious in the treatment of alcoholism. Whereas both compounds
      act pharmacologically differently, there is up to now only limited evidence as to
      whether combined treatment is efficacious and pharmacologically safe. It remains
      to be answered whether data justify the combination of both drugs in clinical
      practice. METHODS: Review of the three pre-clinical and four clinical studies
      that have been published to date on either combined tolerability or efficacy.
      RESULTS: Data available up to now show no occurrence of severe adverse events
      during combined treatment. Diarrhoea and nausea were shown to be the most
      significant side-effects. Whereas pre-clinical studies regarding efficacy of
      combined treatment are not yet conclusive, clinical data show the superiority of
      combined treatment compared with both placebo and acamprosate monotherapy. The
      synergistic effect of combined treatment remained after 12 weeks of drug-free
      follow-up. CONCLUSIONS: The combination of acamprosate with naltrexone in a
      clinical sample seems to be efficacious and safe. Numerous alcohol dependent
      patients could benefit, particularly those that responded insufficiently on
      monotherapeutic treatment with either acamprosate or naltrexone.

PMID- 15456691
TI  - Olfactory functioning in patients with alcohol dependence: impairments in odor
      judgements.
AB  - AIMS: Prior studies indicate that alcohol-dependent patients have impaired
      olfactory sensitivity, odor quality discrimination and identification ability.
      However, olfactory functioning with regard to the immediate, perception driven
      odor associations is unknown. Therefore, this study assessed olfactory judgements
      in nonamnesic and nondemented patients with alcohol dependence. METHODS: Thirty
      alcohol-dependent patients and 30 healthy control subjects, well matched for
      gender, age and smoking status, and screened for olfactory sensitivity, were
      asked to rate intensity, familiarity, edibility and pleasantness of 16 odors
      using visual rating scales. RESULTS: Compared with controls, patients showed
      lower scores in odor familiarity and impaired edibility judgements. These
      impairments were observed bilaterally, were present independently of age, gender,
      general mental abilities and length of abstinence, and not attributable to
      smoking or impaired olfactory sensitivity. No differences between groups were
      found in odor intensity and pleasantness judgements. CONCLUSION: These results
      extend prior findings of alcohol-related olfactory deficits, indicating
      impairments in olfactory processes of odor familiarity and edibility in alcohol
      dependent patients. Although the basis of these deficits is still unknown, our
      finding of a distinct pattern of olfactory functional impairment and sparing
      (intensity, pleasantness) [corrected] suggests that there is no generalized
      [corrected] olfactory dysfunction, but [corrected] neural olfactory networks may
      be affected differently. However, alcoholism appears to be associated with a
      variety of disturbances in olfactory processing [corrected]

PMID- 15456692
TI  - Alcohol brands in young peoples' everyday lives: new developments in marketing.
AB  - New developments in alcohol marketing are likely to be particularly important for
      younger members of the population both because of their use of new technology and
      the role brands play in their lives. This paper discusses the response of young
      people to this marketing, the functions it fulfils for the alcohol industry and
      the need for new policy responses.

PMID- 15456693
TI  - Overexpression of mutated Cu,Zn-SOD in neuroblastoma cells results in
      cytoskeletal change.
AB  - Amyotrophic lateral sclerosis (ALS) involves the progressive degeneration of
      motor neurons in the spinal cord and the motor cortex. It has been shown that 15
      20% of patients with familial ALS (FALS) have defects in the Sod1 gene, which
      encodes Cu,Zn-superoxide dismutase (SOD). To elucidate the pathological role of
      mutated Cu,Zn-SOD, we examined the issue of whether mutated Cu,Zn-SOD affects the
      cell cycle. Mouse neuroblastoma Neuro-2a cells were transfected with human wild
      type or mutated (G37R, G93A) Cu,Zn-SOD. Mutated, Cu,Zn-SOD-transfected cells
      exhibited marked retardation in cell growth and G2/M arrest. They also displayed
      lower reactivity to phalloidin, indicating that the cytoskeleton was disrupted.
      Immunoprecipitation, two-dimensional gel electrophoresis, and Western blot
      analysis indicated that mutated Cu,Zn-SOD associates with actin. Similar results
      were obtained by in vitro incubation experiments with purified actin and mutated
      Cu,Zn-SOD (G93A). These results suggest that mutated Cu,Zn-SOD in FALS causes
      cytoskeletal changes by associating with actin, which subsequently causes G2/M
      arrest and growth retardation.

PMID- 15456694
TI  - Interleukin-13 augments transforming growth factor-beta1-induced tissue inhibitor
      of metalloproteinase-1 expression in primary human airway fibroblasts.
AB  - Tissue inhibitor of metalloproteinase (TIMP)-1 is a potent inhibitor of activated
      matrix metalloproteinases (MMPs) such as gelatinases and collagenases. TIMP-1 is
      induced by transforming growth factor-beta1 (TGF-beta1), but details regarding
      signaling pathways remain unclear. T-helper-2 cytokines also have profibrotic
      properties and can interact with TGF-beta. In the present study, we examined the
      effects of interleukin (IL)-13 (2,500 pM) on TGF-beta1 (200 pM)-induced
      expression of TIMP-1 mRNA and protein in primary human airway fibroblasts
      obtained from 57 human subjects. IL-13 alone had no effect on TIMP-1 mRNA or
      protein expression. However, IL-13 synergistically augmented TGF-beta1-induced
      TIMP-1 mRNA and protein expression (P < 0.001 vs. TGF-beta1 alone). The
      upregulation of TIMP-1 by the combination of TGF-beta1 and IL-13 involved
      increased transcription, with little effect on mRNA stabilization. Initial
      exploration of the pathways leading to the synergy determined that activation of
      the phosphatidylinositol 3-kinase (PI3K)-Akt pathway by IL-13 may have a negative
      effect on TIMP-1 production. The specific PI3K inhibitor LY-294002 in the
      presence of TGF-beta1, IL-13, or the combination of the two caused significant
      increases in TIMP-1 mRNA expression, while LY-294002 increased TIMP-1 protein
      levels in the presence of IL-13 alone. These results suggest that IL-13 augments
      TGF-beta1-induced profibrotic responses at both the mRNA and protein levels.
      Although IL-13 induced activation of PI3K-Akt, the activation did not contribute
      to the synergy observed with TGF-beta1 plus IL-13 in TIMP-1 expression and in
      fact may dampen it. The mechanisms behind the synergy remain to be determined.

PMID- 15456695
TI  - Expression of monocarboxylate transporters in rat ocular tissues.
AB  - The aim of the present study was to determine the distribution of monocarboxylate
      transporter (MCT) subtypes 1-4 in the various structures of the rat eye by using
      a combination of conventional and real-time RT-PCR, immunoblotting, and
      immunohistochemistry. Retinal samples expressed mRNAs encoding all four MCTs.
      MCT1 immunoreactivity was observed in photoreceptor inner segments, Muller cells,
      retinal capillaries, and the two plexiform layers. MCT2 labeling was concentrated
      in the inner and outer plexiform layers. MCT4 immunolabeling was present only in
      the inner retina, particularly in putative Muller cells, and the plexiform
      layers. No MCT3 labeling could be observed. The retinal pigment epithelium
      (RPE)/choroid expressed high levels of MCT1 and MCT3 mRNAs but lower levels of
      MCT2 and MCT4 mRNAs. MCT1 was localized to the apical and MCT3 to the basal
      membrane of the RPE, whereas MCT2 staining was faint. Although MCT1-MCT4 mRNAs
      were all detectable in iris and ciliary body samples, only MCT1 and MCT2 proteins
      were expressed. These were present in the iris epithelium and the nonpigmented
      epithelium of the ciliary processes. MCT4 was localized to the smooth muscle
      lining of large vessels in the iris-ciliary body and choroid. In the cornea, MCT1
      and MCT2 mRNAs and proteins were detectable in the epithelium and endothelium,
      whereas evidence was found for the presence of MCT4 and, to a lesser extent, MCT1
      in the lens epithelium. The unique distribution of MCT subtypes in the eye is
      indicative of the pivotal role that these transporters play in the maintenance of
      ocular function.

PMID- 15456696
TI  - Hypertonic shock inhibits growth factor receptor signaling, induces caspase-3
      activation, and causes reversible fragmentation of the mitochondrial network.
AB  - Hyperosmotic stress can be encountered by the kidney and the skin, as well as
      during treatment of acute brain damage. It can lead to cell cycle arrest or
      apoptosis. Exactly how mammalian cells detect hyperosmolarity and how the cell
      chooses between cell cycle arrest or death remains to be established. It has been
      proposed that hyperosmolarity is detected directly by growth factor receptor
      protein tyrosine kinases. To investigate this, we tested whether growth factors
      and osmotic stress cooperate in the activation of signaling pathways. Receptors
      responded normally to the presence of growth factors, and we observed normal
      levels of GTP-bound Ras under hyperosmotic conditions. In contrast, activation of
      Raf, Akt, ERK1, ERK2, and c-Jun NH2-terminal kinase was strongly reduced. These
      observations suggest that hyperosmotic conditions block signaling directly
      downstream of active Ras. It is thought that apoptotic cell death due to
      environmental stress is initiated by cytochrome c release from the mitochondria.
      Visualization of cytochrome c using immunofluorescence showed that hypertonic
      conditions result in a breakup of the mitochondrial network, which is
      reestablished within 1 h after hypertonic medium is replaced with isotonic
      medium. When we carried out live imaging, we observed that the mitochondrial
      membrane potential disappeared immediately after the onset of hyperosmotic shock.
      Our observations provide new insights into the hypertonic stress response
      pathway. In addition, they show that signaling downstream of Ras and
      mitochondrial dynamics can easily be manipulated by the exposure of cells to
      hyperosmotic conditions.

PMID- 15456697
TI  - Conserved residues F316 and G476 in the concentrative nucleoside transporter 1
      (hCNT1) affect guanosine sensitivity and membrane expression, respectively.
AB  - The functional significance of two highly conserved amino acid residues, F316
      [putative transmembrane domain (TM)7] and G476 (putative TM11), in the
      concentrative nucleoside transporter hCNT1 (SLC28A1) was examined by performing
      site-directed mutagenesis. Conservative mutations at these positions (F316A,
      F316Y, G476A, and G476L) were generated and expressed in Madin-Darby canine
      kidney (MDCK) cells as fusion polypeptides with green fluorescent protein (GFP).
      Unlike wild-type hCNT1, G476A-GFP and G476L-GFP were not expressed in the plasma
      membrane in undifferentiated or differentiated MDCK cells and had no functional
      activity. Like wild-type hCNT1, F316A-GFP and F316Y-GFP were expressed in the
      plasma membrane of undifferentiated MDCK cells and in the apical membrane of
      differentiated MDCK cells. Remarkably, transport of [(3)H]uridine by F316Y-GFP or
      F316A-GFP was highly sensitive to inhibition by guanosine. Furthermore,
      genotyping of exon 11 of hCNT1 (TM7) in a panel of 260 anonymous human DNA
      samples revealed a novel F316H variant (TT>CA; 1/260). When expressed in MDCK
      cells, [(3)H]uridine transport by F316H was also found to be sensitive to
      inhibition by guanosine (IC(50) = 148 microM). The effect of the F316H mutation
      resembles the N4 type nucleoside transporter phenotype previously reported to be
      present in human kidneys. We suggest that the N4 transport system is a naturally
      occurring variant of hCNT1, perhaps at the F316 position. Collectively, our data
      show that G476 is important for correct membrane targeting, folding, and/or
      intracellular processing of hCNT1. In addition, we have discovered that hCNT1
      displays natural variation at position F316 and that the variant F316H confers on
      the transporter an unusual sensitivity to inhibition by guanosine.

PMID- 15456698
TI  - Regulation of Kv4.3 currents by Ca2+/calmodulin-dependent protein kinase II.
AB  - The voltage-dependent K+ channel 4.3 (Kv4.3) is one of the major molecular
      correlates encoding a class of rapidly inactivating K+ currents, including the
      transient outward current in the heart (Ito) and A currents (IA) in neuronal and
      smooth muscle preparations. Recent studies have shown that Ito in human atrial
      myocytes and IA in murine colonic myocytes are modulated by Ca2+/calmodulin
      dependent protein kinase II (CaMKII); however, the molecular target of CaMKII in
      these studies has not been elucidated. We performed experiments to investigate
      whether CaMKII could regulate Kv4.3 currents directly. Inclusion of the
      autothiophosphorylated form of CaMKII in the patch pipette (10 nM) prolonged
      Kv4.3 currents such that the time required to reach 50% inactivation from peak
      more than doubled, with positive shifts in voltage dependence of both activation
      and inactivation. In contrast, the rate of recovery from inactivation was
      accelerated under these conditions. CaMKII-inhibitory peptide or KN-93 produced
      effects opposite to that above; thus the rate of inactivation was increased, and
      recovery from inactivation decreased. A number of mutagenesis experiments were
      conducted on the three candidate CaMKII consensus sequence sites on the channel.
      Mutations at S550A, located at the COOH-terminal region of the channel, resulted
      in currents that inactivated more rapidly but recovered from inactivation at a
      slower rate than that of wild-type controls. In addition, these currents were
      unaffected by dialysis with either autothiophosphorylated CaMKII or the specific
      inhibitory peptide of CaMKII, suggesting that CaMKII slows the inactivation and
      accelerates the rate of recovery from inactivation of Kv4.3 currents by a direct
      effect at S550A, located at the COOH-terminal region of the channel.

PMID- 15456699
TI  - Role of Na+/Ca2+ exchange in regulating cytosolic Ca2+ in cultured human
      pulmonary artery smooth muscle cells.
AB  - A rise in cytosolic Ca2+ concentration ([Ca2+]cyt) in pulmonary artery smooth
      muscle cells (PASMC) is an important stimulus for cell contraction, migration,
      and proliferation. Depletion of intracellular Ca2+ stores opens store-operated
      Ca2+ channels (SOC) and causes Ca2+ entry. Transient receptor potential (TRP)
      cation channels that are permeable to Na+ and Ca2+ are believed to form
      functional SOC. Because sarcolemmal Na+/Ca2+ exchanger has also been implicated
      in regulating [Ca2+]cyt, this study was designed to test the hypothesis that the
      Na+/Ca2+ exchanger (NCX) in cultured human PASMC is functionally involved in
      regulating [Ca2+]cyt by contributing to store depletion-mediated Ca2+ entry. RT
      PCR and Western blot analyses revealed mRNA and protein expression for NCX1 and
      NCKX3 in cultured human PASMC. Removal of extracellular Na+, which switches the
      Na+/Ca2+ exchanger from the forward (Ca2+ exit) to reverse (Ca2+ entry) mode,
      significantly increased [Ca2+]cyt, whereas inhibition of the Na+/Ca2+ exchanger
      with KB-R7943 (10 microM) markedly attenuated the increase in [Ca2+]cyt via the
      reverse mode of Na+/Ca2+ exchange. Store depletion also induced a rise in
      [Ca2+]cyt via the reverse mode of Na+/Ca2+ exchange. Removal of extracellular Na+
      or inhibition of the Na+/Ca2+ exchanger with KB-R7943 attenuated the store
      depletion-mediated Ca2+ entry. Furthermore, treatment of human PASMC with KB
      R7943 also inhibited cell proliferation in the presence of serum and growth
      factors. These results suggest that NCX is functionally expressed in cultured
      human PASMC, that Ca2+ entry via the reverse mode of Na+/Ca2+ exchange
      contributes to store depletion-mediated increase in [Ca2+]cyt, and that blockade
      of the Na+/Ca2+ exchanger in its reverse mode may serve as a potential
      therapeutic approach for treatment of pulmonary hypertension.

PMID- 15456700
TI  - Dynamics of carbohydrate affinities at the cell surface of capacitating bovine
      sperm cells.
AB  - In vivo capacitation of eutherian sperm cells coincides with changes in
      carbohydrate-dependent interaction with the oviduct epithelia (fucose-dependent
      for bovine). Heparin-like glycosaminoglycans (GAG) secreted by the oviduct
      compete for sperm-oviduct binding and are believed to release capacitated sperm
      cells from oviduct epithelia. A biochemical assay to quantify the specificity and
      dynamics of carbohydrate-mediated bovine sperm-oviduct binding is developed.
      Sperm apical plasma membranes (SPM) were purified by a factor eight and
      biotinylated carbohydrate probes were used for quantitative evaluation of
      carbohydrate binding. SPM of fresh sperm showed >12 times higher binding capacity
      for biotinylated fucose than for LewisA. SPM from fresh sperm also efficiently
      bound biotinylated fucoidan and mannan. Binding of biotinylated fucose could be
      inhibited by various mono- and oligosaccharides such as fucoidan, mannan,
      heparin, maltose, and, to a lesser extent, glucose (50% binding at 0.2 mM, 2 mM,
      0.3 microg/ml, 15 mM, 50 mM, respectively). SPM from sperm cells that were in
      vitro capacitated for 4 h in bicarbonate-enriched media (either with or without
      10 microg/ml heparin) showed a 70-85% reduction in fucose binding. This was also
      achieved by follicular fluid or by GAG, both obtained from dominant follicles.
      Total follicular fluid was much more potent in competing with fucose for sperm
      binding than the isolated GAG moieties (50% competition at 0.02 microg/ml, 20
      microg/ml based on number of GAG moieties, respectively). These results support
      the hypothesis that in vivo capacitation of sperm cells is regulated by
      carbohydrate moieties similar to those regulating sperm-oviduct adhesion.

PMID- 15456701
TI  - Blockade of CD86 signaling facilitates a Th2 bias at the maternal-fetal interface
      and expands peripheral CD4+CD25+ regulatory T cells to rescue abortion-prone
      fetuses.
AB  - Intervention in B7 (CD80/CD86)/B7-ligand (CD28/CTLA-4) pathways is an effective
      way of preventing unwanted immune responses, such as allograft rejection.
      Pregnancy maintenance represents maternal tolerance to the fetal allograft, which
      is accompanied by a type 2 helper cell (Th2) bias at the maternal-fetal
      interface. Here, the costimulatory signal of CD86 was selectively blocked, and
      that of CD80 was kept unimpaired by administration of anti-murine CD86 monoclonal
      antibody at the early gestational stage in abortion-prone CBA/JxDBA/2 matings and
      normal pregnant CBA/JxBALB/c matings. It was demonstrated that in vivo blockade
      of CD86 costimulation could suppress maternal immune attack to the fetus by
      shifting cytokines from Th1 predominance to Th2 bias at the maternal-fetal
      interface, and expanding peripheral CD4+CD25+ regulatory T cells, which play an
      important role in the development and maintenance of maternal-fetal tolerance.
      Furthermore, the expression of CD28 and its ligands CD80/CD86 on peripheral
      lymphocytes was down-regulated, whereas that of CTLA-4 was up-regulated, which
      might facilitate the suppressive effect of CD4+CD25+ regulatory T cells on the
      alloreactive T cells. The maternal-fetal immunotolerance induced by CD86 blockade
      decreased fetal resorption in CBA/JxDBA/2 matings, but did not affect normal
      pregnant CBA/JxBALB/c matings. These results suggest that selective blockade of
      CD86 costimulation leads to maternal immune tolerance to embryo antigen, and
      might contribute to a rational immunoregulatory regimen for recurrent spontaneous
      abortion.

PMID- 15456702
TI  - Localization and significance of molecular chaperones, heat shock protein 1, and
      tumor rejection antigen gp96 in the male reproductive tract and during
      capacitation and acrosome reaction.
AB  - Although the molecular basis of sperm-oocyte interaction is unclear, recent
      studies have implicated two chaperone proteins, heat shock protein 1 (HSPD1;
      previously known as heat shock protein 60) and tumor rejection antigen gp96
      (TRA1; previously known as endoplasmin), in the formation of a functional zona
      receptor complex on the surface of mammalian spermatozoa. The current study was
      undertaken to investigate the expression of these chaperones during the ontogeny
      of male germ cells through spermatogenesis, epididymal sperm maturation,
      capacitation, and acrosomal exocytosis. In testicular sections, both HSPD1 and
      TRA1 were closely associated with the mitochondria of spermatogonia and primary
      spermatocytes. However, this labeling pattern disappeared from the male germ line
      during spermiogenesis to become undetectable in testicular spermatozoa.
      Subsequently, these chaperones could be detected in epididymal spermatozoa and in
      previously unreported "dense bodies" in the epididymal lumen. The latter appeared
      in the precise region of the epididymis (proximal corpus), where spermatozoa
      acquire the capacity to recognize and bind to the zona pellucida, implicating
      these structures in the functional remodeling of the sperm surface during
      epididymal maturation. Both HSPD1 and TRA1 were subsequently found to become
      coexpressed on the surface of live mouse spermatozoa following capacitation in
      vitro and were lost once these cells had undergone the acrosome reaction, as
      would be expected of cell surface molecules involved in sperm-egg interaction.
      These data reinforce the notion that these chaperones are intimately involved in
      the mechanisms by which mammalian spermatozoa both acquire and express their
      ability to recognize the zona pellucida.

PMID- 15456703
TI  - Dynamic changes in meiotic progression and improvement of developmental
      competence of pig oocytes in vitro by follicle-stimulating hormone and
      cycloheximide.
AB  - The effects of FSH, LH, and epidermal growth factor (EGF) on the dynamics of
      nuclear maturation and subsequent embryo development were examined in pig oocytes
      cultured either conventionally or after preincubation with cycloheximide (CHX).
      In conventional culture, FSH or EGF significantly increased the rate of
      attainment of metaphase II (MII) for both gilt (50.0%+/-4.2% and 54.8%+/-4.3%,
      respectively; control, 5.8%+/-1.8%; P<0.001) and sow (87.6%+/-3.4% and 78.8%+/
      3.9%, respectively; control, 7.8%+/-2.5%; P<0.001) oocytes. Gilt oocytes treated
      with both FSH and EGF showed an additive response (93.7%+/-2.1%). Treatment with
      LH had no effect. Preincubation with CHX caused the majority (84-100%) of both
      gilt and sow oocytes to undergo germinal vesicle breakdown. Compared to those
      treated with LH and/or EGF (both>80%), fewer FSH-treated oocytes reached
      metaphase I (43.8%+/-5.3%, P<0.001) by 14 h and MII (48.4%+/-5.9%, P<0.001) by 24
      h, although the majority (71%) did mature to MII by 36 h after removal of CHX.
      After in vitro fertilization, higher proportions of both CHX-pretreated and
      untreated, FSH-exposed oocytes cleaved (71.3%+/-2.9% and 75.3%+/-3.1%,
      respectively) compared with those not treated with FSH (37.7%+/-3.0% and 43.0%+/
      2.9%, respectively; P<0.001). Pretreatment with CHX significantly increased
      blastocyst yield for both FSH-treated (32.8%+/-2.0% and 10.3%+/-1.5%,
      respectively; P<0.001) and untreated (16.7%+/-1.5% and 9.4%+/-1.2%, respectively;
      P<0.001) oocytes. Polyspermy rates were unaffected. In conclusion, pig oocytes
      meiotically arrested by CHX before maturation retain and improve their
      developmental competence. FSH stimulates nuclear maturation but slows meiotic
      progression.

PMID- 15456704
TI  - Genetic selection of mouse male germline stem cells in vitro: offspring from
      single stem cells.
AB  - Spermatogenesis originates from a small population of spermatogonial stem cells.
      These cells are believed to divide infinitely and support spermatogenesis
      throughout life in the male. In this investigation, we examined the possibility
      of deriving transgenic offspring from single spermatogonial stem cells.
      Spermatogonial stem cells were transfected in vitro with a plasmid vector
      containing a drug resistant gene. Stably transfected stem cell clones were
      isolated by in vitro drug selection; these clones were expanded and used to
      produce transgenic progeny following spermatogonial transplantation into
      infertile recipients. An average of 49% of the offspring carried the transgene,
      and the recipient mice continued to produce monoclonal transgenic progeny a year
      after transplantation. Thus, a somatic cell-based genetic approach can be used to
      modify and select clones of spermatogonial stem cells in a manner similar to
      embryonic stem cells. The feasibility of genetic selection using postnatal
      spermatogonial stem cells demonstrates their extensive proliferative potential
      and provides the opportunity to develop new methods for generating stable animal
      transgenics or for germline gene therapy.

PMID- 15456705
TI  - Training-dependent plasticity in patients with multiple sclerosis.
AB  - Cortical reorganization has been demonstrated in the motor network that mediates
      performance of a motor task in patients with multiple sclerosis. How this network
      responds to motor training is not known. This study examined functional MRI
      (fMRI) activation patterns associated with performance of a motor task,
      consisting of repetition of directionally specific voluntary thumb movements,
      before and after motor training in a group of multiple sclerosis patients with
      mild motor impairment of the right upper extremity. Patients and healthy subjects
      were scanned in one session before, during and after a 30 min training period.
      fMRI data obtained during rest, thumb flexion (trained movement) and thumb
      extension (untrained movement) were analysed using random effects analysis
      (SPM99). Motor kinematics of training motions and EMG from the resting hand were
      monitored with an accelerometer and surface EMG electrodes. Kinematics of thumb
      movements before, during and after training were comparable in the absence of
      mirror EMG activity in the resting hand. Before training, thumb movements
      elicited more prominent activation of the contralateral dorsal premotor cortex
      [PMd, Brodmann area (BA) 6] in multiple sclerosis patients than in controls.
      After training, unlike the control group, multiple sclerosis patients did not
      exhibit task-specific reductions in activation in the contralateral primary
      somatosensory (S1), motor (M1) and adjacent parietal association (BA 40)
      cortices. These results indicate that patients engage the contralateral PMd more
      than controls in order to perform directionally specific movements before
      training. The absence of training-dependent reductions in activation in S1, M1
      and BA 40 is consistent with a decreased capacity to optimize recruitment of the
      motor network with practice.

PMID- 15456706
TI  - Does induced hypertension reduce cerebral ischaemia within the traumatized human
      brain?
AB  - Recent changes in published guidelines for the management of patients with severe
      head injury are based on data showing that aggressive maintenance of cerebral
      perfusion pressure (CPP) can worsen outcome due to extracranial complications of
      therapy. However, it remains unclear whether CPP augmentation could reduce
      cerebral ischaemia, a finding which might prompt the search for CPP augmentation
      protocols that avoid these extracranial complications. We studied 10 healthy
      volunteers and 20 patients within 6 days of closed head injury. All subjects
      underwent imaging of cerebral blood flow (CBF), blood volume (CBV), oxygen
      metabolism (CMRO2) and oxygen extraction fraction (OEF) using 15O PET. In
      addition, for patients, the EEG power ratio index (PRI), burst suppression ratio
      and somatosensory evoked potentials (SEP) were obtained and CPP was increased
      from 68 +/- 4 to 90 +/- 4 mmHg using an infusion of norepinephrine and
      measurements were repeated. Following elevation of CPP, CBF and CBV were
      increased and CMRO2 and OEF were reduced (P < 0.001 for all comparisons). Regions
      with a reduction in CMRO2 were associated with the greatest reduction in OEF (r2
      = 0.3; P < 0.0001). Although CPP elevation produced a significant fall in the
      ischaemic brain volume (IBV) (from 15 +/- 16 to 5 +/- 4 ml; P < 0.01) and
      improved flow metabolism coupling, the IBV was small and clinically insignificant
      in the majority of these patients. However, the reduction in IBV was directly
      related to the baseline IBV (r2 = 0.97; P < 0.001) and patients with large
      baseline IBV showed substantial and clinically significant reductions. CPP
      augmentation increased the EEG PRI (5.0 +/- 1.5 versus 4.3 +/- 1.4, P < 0.01),
      implying an overall decrease in neural activity, but these changes did not
      correlate with the reduction in CMRO2 and there was no change in SEP cortical
      amplitude (N20-P27). These data provide support for recent changes in recommended
      CPP levels for head injury management across populations of patients with
      significant head injury. However, they do not provide guidance on whether the
      intervention may be more appropriate at earlier stages after injury, or in
      patients selected because of high baseline IBV. It also remains unclear whether
      CPP values below 65 mmHg can be safely used in this population. Clarification of
      the significance of a reduction in CMRO2 and neuronal electrical function will
      require further study.

PMID- 15456707
TI  - Differential responses in three thalamic nuclei in moderately disabled, severely
      disabled and vegetative patients after blunt head injury.
AB  - In vivo imaging techniques have indicated for many years that there is loss of
      white matter after human traumatic brain injury (TBI) and that the loss is
      inversely related to cognitive outcome. However, correlated, quantitative
      evidence for loss of neurons from either the cerebral cortex or the diencephalon
      is largely lacking. There is some evidence in models of TBI that neuronal loss
      occurs within the thalamus, but no systematic studies of such loss have been
      undertaken in the thalamus of humans after blunt head injury. We have undertaken
      a stereological analysis of changes in numbers of neurons within the dorsomedial,
      ventral posterior and lateral posterior thalamic nuclei in patients assessed by
      the Glasgow Outcome Scale as moderately disabled (n = 9), severely disabled (n =
      12) and vegetative (n = 10) head-injured patients who survived between 6 h and 3
      years, and controls (n = 9). In histological sections at the level of the lateral
      geniculate body, the cross-sectional area of each nucleus and the number and the
      mean size of neurons within each nucleus was quantified. A statistically
      significant loss of cross-sectional area and number of neurons occurred in the
      dorsomedial nucleus in moderately disabled, and both the dorsomedial and ventral
      posterior thalamic nuclei in severely disabled and vegetative head-injured
      patients. However, there was no change in neuronal cell size. In the lateral
      posterior nucleus, despite a reduction in mean cell size, there was not a
      significant change in either nuclear area or number of neurons in cases of
      moderately disabled, severely disabled or vegetative patients. We posit, although
      detailed neuropsychological outcome for the patients included within this study
      was not available, that neuronal loss in the dorsomedial thalamus in moderately
      and severely disabled and vegetative patients may be the structural basis for the
      clinical assessment in the Glasgow Outcome Scale. In severely disabled and
      vegetative patients, loss of neurons from the ventral posterior thalamic nucleus
      may also reflect loss of response to afferent stimuli.

PMID- 15456708
TI  - Angiogenesis imaging in the post-genomic era.

PMID- 15456709
TI  - Translating angiogenesis research into the clinic: the challenges ahead.
AB  - The field of angiogenesis research has evolved to become one of the most rapidly
      growing biomedical disciplines. The interest in basic angiogenesis research is
      sparked by the translational therapeutic potential aimed at developing anti
      angiogenesis as a novel therapeutic modality for tumours and a number of non
      oncological diseases, such as rheumatoid arthritis, psoriasis, diabetic
      retinopathy and age-dependent macula degeneration. The molecular determinants of
      the angiogenic cascade have been characterized in great detail over the last few
      years. Likewise, intense ongoing efforts are aimed at identifying and validating
      additional vascular specific determinants that may be exploited as therapeutic
      targets for pro-angiogenic and anti-angiogenic therapy. At the same time, a large
      number of angiomodulatory compounds are in various phases of clinical trials.
      These include the neutralizing vascular endothelial growth factor (VEGF) antibody
      Avastin, which has successfully passed phase III clinical trials for the
      combination with chemotherapy in colorectal cancers. In view of the dramatic
      progress in basic angiogenesis research, surprisingly little is known about the
      nature of the neovasculature in human tumours. The inclusion and exclusion
      criteria of clinical trials of anti-angiogenic compounds are devoid of
      angiogenesis-related parameters and reliable biomarkers to trace the efficacy of
      an anti-angiogenic intervention are largely missing. Based on a brief review of
      the biology of the angiogenic cascade, this review provides an overview of the
      current concepts of the angiogenic vasculature in human tumours and discusses
      some key unanswered questions in translating angiogenesis research into the
      clinic.

PMID- 15456710
TI  - Microenvironmental and cellular consequences of altered blood flow in tumours.
AB  - Tumour angiogenesis is triggered by various signals characteristic of the tumour
      microenvironment, including low oxygen tension, low extracellular pH and low
      glucose concentration. Tumour microvasculature is chaotic, producing perfusion
      heterogeneities which can be visualized by MRI and other modalities. Inefficient
      perfusion in tumours produces regions of transient and chronic hypoxia. Tumour
      hypoxia is associated with adverse clinical outcomes and reduced patient
      survival. Hypoxia may be a factor in activation of extracellular matrix-degrading
      proteases, and some studies have correlated primary tumour hypoxia with
      likelihood of tumour cell dissemination. Exposure to hypoxia either induces or
      selects for cells that are hyperglycolytic, and this in turn produces local
      acidosis which is also a common feature of solid tumours. Increased glucose
      uptake in hyperglycolyzing tumour cells is the basis of lesion-visualization in
      positron emission tomography using 18F-fluorodeoxyglucose. Tumour acidity can
      reduce the effectiveness of weak-base drugs, but can be exploited to increase the
      anti-tumour activity of weak-acid chemotherapeutics. Evidence linking tumour
      acidity with increased activity of several extracellular matrix-degrading enzyme
      systems is examined. High levels of lactate, another end-product of glycolysis,
      in primary lesions have been correlated with increased likelihood of metastasis.
      In the numerous studies correlating hypoxia, acidity and lactate with metastasis,
      the direction of the causality has not been adequately established. We
      hypothesize that adoption of a hyperglycolytic phenotype is a necessary feature
      of carcinogenesis itself, and confers a survival and proliferative advantage to
      tumour cells over surrounding normal cells. Empirical evidence supporting this
      "acid-mediated tumour invasion" model is discussed.

PMID- 15456711
TI  - Measuring tumour vascular response to antivascular and antiangiogenic drugs.
AB  - The tumour vasculature is an attractive target for therapy because of its
      accessibility to blood-borne anticancer agents and the reliance of most tumour
      cells on an intact vascular supply for their survival. For convenience,
      therapeutic targeting of the tumour vasculature can be divided into
      antiangiogenic approaches, which target the process of new blood vessel
      development and antivascular approaches, which target the established tumour
      vasculature. Many agents are now in clinical trial for the treatment of cancer by
      these methods. The main aim of this article is to describe the vascular effects
      of some of these agents and identify suitable end-points for measuring efficacy
      in early clinical trials. For drugs which are active below their maximum
      tolerated dose (MTD), measurement of vascular end-points is required to determine
      the most effective dosing/scheduling protocols. In addition, many of the current
      and developing antiangiogenic agents have additional mechanisms of action
      unrelated to angiogenesis per se, requiring measurement of vascular end-points to
      understand their mechanisms of action. Measurement of tumour microvascular
      density (MVD) from tumour biopsies is a common method for assessing the efficacy
      of antiangiogenic drugs. The limitations of this method and alternative end
      points, which take into account vascular function, are discussed. Pre-clinical
      data regarding tumour response to the antivascular agent combretastatin A-4 3-0
      phosphate (CA-4-P) are discussed in the context of guiding clinical trial
      planning. Finally, the accessibility of vascular end-points for clinical imaging
      is addressed.

PMID- 15456712
TI  - Perfusion CT for the assessment of tumour vascularity: which protocol?
AB  - Perfusion CT is a technique that can be readily incorporated into the existing CT
      protocols that continue to provide the mainstay for anatomical imaging in
      oncology to provide an in vivo marker of tumour angiogenesis. By capturing
      physiological information reflecting the tumour vasculature, perfusion CT can be
      useful for diagnosis, risk-stratification and therapeutic monitoring. However, a
      wide range of perfusion CT techniques have evolved and the various commercial
      implementations advocate different acquisition protocols and processing methods.
      Acquisition choices include first pass studies or delayed imaging, temporal
      resolution versus image noise, and single location sequences or multiple spiral
      acquisitions. Data processing may be semi-quantitative or, using either
      compartmental analysis or deconvolution, produce results that are quantified in
      absolute physiological terms such as perfusion, blood volume and permeability.
      This article discusses the advantages and disadvantages of the more common CT
      perfusion protocols and offers proposals that could allow for easier comparison
      between studies employing different techniques.

PMID- 15456713
TI  - Angiogenesis imaging--ultrasound.

PMID- 15456714
TI  - Positron emission tomographic imaging of angiogenesis and vascular function.
AB  - Surrogate markers of clinical outcome are important in anticancer drug research,
      since clinical criteria of response develop only slowly and may be confounded by
      other processes than drug effect. The need for surrogate outcome markers is
      especially great with newer agents that may act by tumour stabilization as
      opposed to shrinkage. Neoplastic angiogenesis is associated with a number of
      detectable changes at molecular and microcirculatory levels. Therefore, direct
      study of angiogenic molecular biology and tumour circulation before during and
      after treatment may offer useful surrogate markers for vascular-targeted
      therapies. The main advantage of radiotracer imaging with positron emission
      tomography (PET) is its functional specificity. This article will review two main
      areas: (a) the methodology behind PET imaging of tumour blood supply with 15O
      oxygen labelled compounds; and (b) newer tracers in development as markers of
      angiogenetic biology.

PMID- 15456715
TI  - MRI for assessing antivascular cancer treatments.
AB  - Selective antiangiogenesis and vascular targeting drugs hold out the promise of
      improved efficacy and tolerability for anticancer treatments. Early phase 1 drug
      trials have shown good tolerability for antiangiogenesis agents with biological
      activity below the maximum tolerated dose. Advanced clinical trials have
      demonstrated that morphological assessments of tumour response are of limited
      value in gauging the efficacy of treatment. MRI is a versatile technique which is
      sensitive to contrast mechanisms that can be affected by antivascular treatments;
      this use for MRI has been validated in xenografts and humans. Dynamic contrast
      enhanced MRI (DCE-MRI), which demonstrates tissue perfusion and permeability, is
      being used clinically as a pharmacodynamic indicator of biological activity for
      antivascular cancer drugs. Early data show that DCE-MRI studies can define the
      biologically active dose and predict the efficacy of treatment on the basis of
      changes observed. MRI with macromolecular contrast media (MMCM) depicts
      microvessel permeability and fractional plasma volume. Xenograft studies with
      MMCM have shown great promise for evaluating antivascular treatments but this has
      not been used clinically. Intrinsic susceptibility-weighted MRI, which is
      sensitive to blood oxygenation and flow, is emerging as a technique that may be
      able to monitor vascular targeting therapies.

PMID- 15456716
TI  - Angiogenesis imaging in man: a personal view from the pharmaceutical industry.
AB  - The imaging of angiogenesis in human disease represents an exciting prospect for
      those involved in the drug development process. With an increasing focus on the
      therapeutic modulation of angiogenesis in man, the development of technologies
      capable of monitoring angiogenic drug interventions non-invasively should be
      welcomed.

PMID- 15456717
TI  - Antivascular cancer treatments: imaging biomarkers in pharmaceutical drug
      development.

PMID- 15456718
TI  - Assessment of antiangiogenic and antivascular therapeutics using MRI:
      recommendations for appropriate methodology for clinical trials.

PMID- 15456719
TI  - Imaging in antiangiogenesis trial: a clinical trials radiology perspective.
AB  - Traditional approaches for treating cancer have largely focused on the ability of
      chemotherapy, and to a lesser extent radiation therapy, to destroy tumour cells.
      Recent developments in antiangiogenesis treatments require a fundamental shift in
      the radiological and imaging paradigms associated with evaluating response.
      Proper design and execution of any clinical trial involving imaging angiogenesis
      requires satisfactory consideration of a number of strategies and an in-depth
      understanding of different imaging techniques such as dynamic contrast enhanced
      MRI and CT, contrast-enhanced ultrasound and positron emission tomography. In
      particular, for imaging, the strategies can be divided into issues that need to
      be addressed during the protocol planning phase, and strategies that need to be
      addressed during the execution phase. Furthermore, clinical trials are usually
      subject to stringent regulations surrounding traceability and reproducibility
      that need to be followed before the regulatory authorities will accept the
      integrity of the data. This paper elaborates on the above strategies and outlines
      certain aspects, or tactics, that need to be considered while preparing for a
      multicentre clinical trial that involves imaging angiogenesis.

PMID- 15456720
TI  - Testis-specific TAF homologs collaborate to control a tissue-specific
      transcription program.
AB  - Alternate forms of the PolII transcription initiation machinery have been
      proposed to play a role in selective activation of cell-type-specific gene
      expression programs during cellular differentiation. The cannonball (can) gene of
      Drosophila encodes a homolog of a TBP-associated factor (dTAF5) protein expressed
      only in spermatocytes, where it is required for normal transcription of genes
      required for spermatid differentiation. We show that Drosophila primary
      spermatocytes also express four additional tissue-specific TAFs: nht (homolog of
      dTAF4), mia (homolog of dTAF6), sa (homolog of dTAF8) and rye (homolog of
      dTAF12). Mutations in nht, mia and sa have similar effects in primary
      spermatocytes on transcription of several target genes involved in spermatid
      differentiation, and cause the same phenotypes as mutations in can, blocking both
      meiotic cell cycle progression and spermatid differentiation. The nht, mia, sa
      and rye proteins contain histone fold domain dimerization motifs. The nht and rye
      proteins interact structurally when co-expressed in bacteria, similarly to their
      generally expressed homologs TAF4 and TAF12, which heterodimerize. Strikingly,
      the structural interaction is tissue specific: nht did not interact with dTAF12
      and dTAF4 did not interact with rye in a bacterial co-expression assay. We
      propose that the products of the five Drosophila genes encoding testis TAF
      homologs collaborate in an alternative TAF-containing protein complex to regulate
      a testis-specific gene expression program in primary spermatocytes required for
      terminal differentiation of male germ cells.

PMID- 15456721
TI  - Drosophila homeodomain protein Nkx6 coordinates motoneuron subtype identity and
      axonogenesis.
AB  - The regulatory networks acting in individual neurons to control their stereotyped
      differentiation, connectivity, and function are not well understood. Here, we
      demonstrate that homeodomain protein Nkx6 is a key member of the genetic network
      of transcription factors that specifies neuronal fates in Drosophila. Nkx6
      collaborates with the homeodomain protein Hb9 to specify ventrally projecting
      motoneuron fate and to repress dorsally projecting motoneuron fate. While Nkx6
      acts in parallel with hb9 to regulate motoneuron fate, we find that Nkx6 plays a
      distinct role to promote axonogenesis, as axon growth of Nkx6-positive
      motoneurons is severely compromised in Nkx6 mutant embryos. Furthermore, Nkx6 is
      necessary for the expression of the neural adhesion molecule Fasciclin III in
      Nkx6-positive motoneurons. Thus, this work demonstrates that Nkx6 acts in a
      specific neuronal population to link neuronal subtype identity to neuronal
      morphology and connectivity.

PMID- 15456722
TI  - Zebrafish and fly Nkx6 proteins have similar CNS expression patterns and regulate
      motoneuron formation.
AB  - Genes belonging to the Nkx, Gsh and Msx families are expressed in similar
      dorsovental spatial domains of the insect and vertebrate central nervous system
      (CNS), suggesting the bilaterian ancestor used this genetic program during CNS
      development. We have investigated the significance of these similar expression
      patterns by testing whether Nkx6 proteins expressed in ventral CNS of zebrafish
      and flies have similar functions. In zebrafish, Nkx6.1 is expressed in early-born
      primary and later-born secondary motoneurons. In the absence of Nkx6.1, there are
      fewer secondary motoneurons and supernumerary ventral interneurons, suggesting
      Nkx6.1 promotes motoneuron and suppresses interneuron formation. Overexpression
      of fish or fly Nkx6 is sufficient to generate supernumerary motoneurons in both
      zebrafish and flies. These results suggest that one ancestral function of Nkx6
      proteins was to promote motoneuron development.

PMID- 15456723
TI  - Interaction of Polycomb-group proteins controlling flowering in Arabidopsis.
AB  - In Arabidopsis, the EMBYRONIC FLOWER2 (EMF2), VERNALISATION2 (VRN2) and
      FERTILISATION INDEPENDENT ENDOSPERM2 (FIS2) genes encode related Polycomb-group
      (Pc-G) proteins. Their homologues in animals act together with other Pc-G
      proteins as part of a multimeric complex, Polycomb Repressive Complex 2 (PRC2),
      which functions as a histone methyltransferase. Despite similarities between the
      fis2 mutant phenotype and those of some other plant Pc-G members, it has remained
      unclear how the FIS2/EMF2/VRN2 class Pc-G genes interact with the others. We have
      identified a weak emf2 allele that reveals a novel phenotype with striking
      similarity to that of severe mutations in another Pc-G gene, CURLY LEAF (CLF),
      suggesting that the two genes may act in a common pathway. Consistent with this,
      we demonstrate that EMF2 and CLF interact genetically and that this reflects
      interaction of their protein products through two conserved motifs, the VEFS
      domain and the C5 domain. We show that the full function of CLF is masked by
      partial redundancy with a closely related gene, SWINGER (SWN), so that null clf
      mutants have a much less severe phenotype than emf2 mutants. Analysis in yeast
      further indicates a potential for the CLF and SWN proteins to interact with the
      other VEFS domain proteins VRN2 and FIS2. The functions of individual Pc-G
      members may therefore be broader than single mutant phenotypes reveal. We suggest
      that plants have Pc-G protein complexes similar to the Polycomb Repressive
      Complex2 (PRC2) of animals, but the duplication and subsequent diversification of
      components has given rise to different complexes with partially discrete
      functions.

PMID- 15456724
TI  - Hedgehog and Decapentaplegic instruct polarized growth of cell extensions in the
      Drosophila trachea.
AB  - The migration of cellular extensions is guided by signals from tissues with which
      they contact. Many axon guidance molecules regulate growth cone migration by
      directly regulating actin cytoskeletal dynamics. Secreted morphogens control
      global patterns of cell fate decisions during organogenesis through
      transcriptional regulation, and constitute another class of guidance molecules.
      We have investigated the guidance roles of the morphogens Hedgehog and
      Decapentaplegic during directed outgrowth of cytoplasmic extensions in the
      Drosophila trachea. A subset of tracheal terminal cells adheres to the internal
      surface of the epidermis and elongates cytoplasmic processes called terminal
      branches. Hedgehog promotes terminal branch spreading and its extension over the
      posterior compartment of the epidermis. Decapentaplegic, which is expressed at
      the onset of terminal branching, restricts dorsal extension of the terminal
      branch and ensures its monopolar growth. Orthogonal expression of Hedgehog and
      Decapentaplegic in the epidermis instructs monopolar extension of the terminal
      branch along the posterior compartment, thereby matching the pattern of airway
      growth with that of the epidermis.

PMID- 15456725
TI  - The receptor tyrosine kinase Off-track is required for layer-specific neuronal
      connectivity in Drosophila.
AB  - The nervous system in many species consists of multiple neuronal cell layers,
      each forming specific connections with neurons in other layers or other regions
      of the brain. How layer-specific connectivity is established during development
      remains largely unknown. In the Drosophila adult visual system, photoreceptor (R
      cell) axons innervate one of two optic ganglia layers; R1-R6 axons connect to the
      lamina layer, while R7 and R8 axons project through the lamina into the deeper
      medulla layer. Here, we show that the receptor tyrosine kinase Off-track (Otk) is
      specifically required for lamina-specific targeting of R1-R6 axons. Otk is highly
      expressed on R1-R6 growth cones. In the absence of otk, many R1-R6 axons connect
      abnormally to medulla instead of innervating lamina. We propose that Otk is a
      receptor or a component of a receptor complex that recognizes a target-derived
      signal for R1-R6 axons to innervate the lamina layer.

PMID- 15456726
TI  - Requirement for Par-6 and Bazooka in Drosophila border cell migration.
AB  - Polarized epithelial cells convert into migratory invasive cells during a number
      of developmental processes, as well as when tumors metastasize. Much has been
      learned recently concerning the molecules and mechanisms that are responsible for
      generating and maintaining epithelial cell polarity. However, less is known about
      what becomes of epithelial polarity proteins when various cell types become
      migratory and invasive. Here, we report the localization of several apical
      epithelial proteins, Par-6, Par-3/Bazooka and aPKC, during border cell migration
      in the Drosophila ovary. All of these proteins remained asymmetrically
      distributed throughout migration. Moreover, depletion of either Par-6 or Par
      3/Bazooka by RNAi resulted in disorganization of the border cell cluster and
      impaired migration. The distributions of several transmembrane proteins required
      for migration were abnormal following Par-6 or Par-3/Bazooka downregulation,
      possibly accounting for the migration defects. Taken together, these results
      indicate that cells need not lose apical/basal polarity in order to invade
      neighboring tissues and in some cases even require such polarity for proper
      motility.

PMID- 15456727
TI  - Distinct GATA6- and laminin-dependent mechanisms regulate endodermal and
      ectodermal embryonic stem cell fates.
AB  - This study investigates the establishment of alternative cell fates during
      embryoid body differentiation when ES cells diverge into two epithelia simulating
      the pre-gastrulation endoderm and ectoderm. We report that endoderm
      differentiation and endoderm-specific gene expression, such as expression of
      laminin 1 subunits, is controlled by GATA6 induced by FGF. Subsequently,
      differentiation of the non-polar primitive ectoderm into columnar epithelium of
      the epiblast is induced by laminin 1. Using GATA6 transformed Lamc1-null endoderm
      like cells, we demonstrate that laminin 1 exhibited by the basement membrane
      induces epiblast differentiation and cavitation by cell-to-matrix/matrix-to-cell
      interactions that are similar to the in vivo crosstalk in the early embryo.
      Pharmacological and dominant-negative inhibitors reveal that the cell shape
      change of epiblast differentiation requires ROCK, the Rho kinase. We also show
      that pluripotent ES cells display laminin receptors; hence, these stem cells may
      serve as target for columnar ectoderm differentiation. Laminin is not bound by
      endoderm derivatives; therefore, the sub-endodermal basement membrane is anchored
      selectively to the ectoderm, conveying polarity to its assembly and to the
      differentiation induced by it. Unique to these interactions is their flow through
      two cell layers connected by laminin 1 and their involvement in the
      differentiation of two epithelia from the same stem cell pool: one into endoderm
      controlled by FGF and GATA6; and the other into epiblast regulated by laminin 1
      and Rho kinase.

PMID- 15456728
TI  - The Lim homeobox gene Lhx2 is required for olfactory sensory neuron identity.
AB  - Progenitor cells in the mouse olfactory epithelium generate over a thousand
      subpopulations of neurons, each expressing a unique odorant receptor (OR) gene.
      This event is under the control of spatial cues, since neurons in different
      epithelial regions are restricted to express region-specific subsets of OR genes.
      We show that progenitors and neurons express the LIM-homeobox gene Lhx2 and that
      neurons in Lhx2-null mutant embryos do not diversify into subpopulations
      expressing different OR genes and other region-restricted genes such as Nqo1 and
      Ncam2. Lhx2-/- embryos have, however, a normal distribution of Mash1-positive and
      neurogenin 1-positive neuronal progenitors that leave the cell cycle, acquire pan
      neuronal traits and form axon bundles. Increased cell death in combination with
      increased expression of the early differentiation marker Neurod1, as well as
      reduced expression of late differentiation markers (Galphaolf and Omp), suggests
      that neuronal differentiation in the absence of Lhx2 is primarily inhibited at,
      or immediate prior to, onset of OR expression. Aberrant regional expression of
      early and late differentiation markers, taken together with unaltered region
      restricted expression of the Msx1 homeobox gene in the progenitor cell layer of
      Lhx2-/- embryos, shows that Lhx2 function is not required for all aspects of
      regional specification of progenitors and neurons. Thus, these results indicate
      that a cell-autonomous function of Lhx2 is required for differentiation of
      progenitors into a heterogeneous population of individually and regionally
      specified mature olfactory sensory neurons.

PMID- 15456729
TI  - A vertebrate crossveinless 2 homologue modulates BMP activity and neural crest
      cell migration.
AB  - Previous work has revealed that proteins that bind to bone morphogenetic proteins
      (BMPs) and inhibit their signalling have a crucial role in the spatial and
      temporal regulation of cell differentiation and cell migration by BMPs. We have
      identified a chick homologue of crossveinless 2, a Drosophila gene that was
      identified in genetic studies as a promoter of BMP-like signalling. Chick Cv-2
      has a conserved structure of five cysteine-rich repeats similar to those found in
      several BMP antagonists, and a C-terminal Von Willebrand type D domain. Cv-2 is
      expressed in the chick embryo in a number of tissues at sites at which elevated
      BMP signalling is required. One such site of expression is premigratory neural
      crest, in which at trunk levels threshold levels of BMP activity are required to
      initiate cell migration. We show that, when overexpressed, Cv-2 can weakly
      antagonise BMP4 activity in Xenopus embryos, but that in other in vitro assays Cv
      2 can increase the activity of co-expressed BMP4. Furthermore, we find that
      increased expression of Cv-2 causes premature onset of trunk neural crest cell
      migration in the chick embryo, indicative of Cv-2 acting to promote BMP activity
      at an endogenous site of expression. We therefore propose that BMP signalling is
      modulated both by antagonists and by Cv-2 that acts to elevate BMP activity.

PMID- 15456730
TI  - Canonical Wnt activity regulates trunk neural crest delamination linking
      BMP/noggin signaling with G1/S transition.
AB  - Delamination of premigratory neural crest cells depends on a balance between
      BMP/noggin and on successful G1/S transition. Here, we report that BMP regulates
      G1/S transition and consequent crest delamination through canonical Wnt
      signaling. Noggin overexpression inhibits G1/S transition and blocking G1/S
      abrogates BMP-induced delamination; moreover, transcription of Wnt1 is stimulated
      by BMP and by the developing somites, which concomitantly inhibit noggin
      production. Interfering with beta-catenin and LEF/TCF inhibits G1/S transition,
      neural crest delamination and transcription of various BMP-dependent genes, which
      include Cad6B, Pax3 and Msx1, but not that of Slug, Sox9 or FoxD3. Hence, we
      propose that developing somites inhibit noggin transcription in the dorsal tube,
      resulting in activation of BMP and consequent Wnt1 production. Canonical Wnt
      signaling in turn stimulates G1/S transition and generation of neural crest cell
      motility independently of its proposed role in earlier neural crest
      specification.

PMID- 15456731
TI  - Passive immunization with the anti-HIV-1 human monoclonal antibody (hMAb) 4E10
      and the hMAb combination 4E10/2F5/2G12.
AB  - OBJECTIVES: To study the safety, immunogenicity and pharmacokinetics of the human
      monoclonal antibody (hMAb) 4E10 alone and in combination with the hMAbs 2F5 and
      2G12 in HIV-1-infected persons. MATERIALS AND METHODS: Eight healthy volunteers
      with > or =350 CD4 cells/mm3 and < or =100 000 HIV-1 RNA copies/mL were enrolled,
      seven finished the study. A single 4E10 infusion was administered on day 0,
      followed by three doses of the hMAb combination 4E10/2F5/2G12 on days 7, 14 and
      21 (total amount 8.5 g). Safety was assessed by physical examination, blood
      chemistry, complete blood cell count and recording of adverse events. 4E10, 2F5
      and 2G12 plasma levels were determined before and at the end of each infusion and
      during the 7 week follow-up. RESULTS: No drug-related adverse events were
      observed throughout the study. The median plasma concentrations immediately after
      the first infusion were 371, 253 and 139 microg/mL for 4E10, 2F5 and 2G12.
      Multiple infusions resulted in maximum plasma concentrations of 407, 294 and 210
      microg/mL for 4E10, 2F5, and 2G12, respectively. The median elimination half
      lives (t1/2beta) were 6.6, 3.2 and 14.1 days for 4E10, 2F5 and 2G12. A low level
      antibody response against 2G12 was found in two patients. CONCLUSION: This Phase
      I trial showed that the hMAb 4E10 can be safely administered, both alone and in
      combination with 2F5 and 2G12 to HIV-1-infected patients.

PMID- 15456732
TI  - Evaluation of carvacrol and eugenol as prophylaxis and treatment of vaginal
      candidiasis in an immunosuppressed rat model.
AB  - OBJECTIVES: Anticandidal activity of carvacrol and eugenol, the major phenolic
      components of oregano and clove essential oils, respectively, were tested in
      vivo. METHODS: Efficacy evaluation of carvacrol and eugenol in the prophylaxis
      and treatment of experimental vaginal candidiasis was performed in
      immunosuppressed rats. The anticandidal activity was analysed by microbiological
      and histological techniques and was compared with that of nystatin. RESULTS:
      Microbiologically, prophylactic treatment with carvacrol eradicated the vaginal
      fungal burden of infected rats, whereas eugenol reduced the number of colony
      counts of Candida albicans in vaginas of infected rats by 98.9% 10 days after
      inoculation. Therapeutic treatment for 7 consecutive days with carvacrol was able
      to eradicate the vaginal candidal burden in 7/9 of the infected rats and reduced
      the number of colony counts of C. albicans in vaginas of the two remaining rats
      by 98%. Treatment with eugenol completely cured 2/9 of the infected animals, but
      the 7/9 still infected showed an 84% reduction of colony counts of C. albicans in
      their vaginas. Histologically, in all treated rats, no Candida organisms were
      found in the lumina of the vagina; this was in contrast to control groups in
      which many yeasts, strongly stained with periodic acid-Schiff, were observed. The
      results obtained with nystatin used at 10-fold minimal inhibitory concentration
      confirm the validity of this model. CONCLUSIONS: Carvacrol and eugenol could be
      considered as promising products in the treatment of vaginal candidiasis. This
      work is a preliminary contribution to the development of a new generation of
      efficient and natural antifungal agents for curative treatment and prophylaxis.

PMID- 15456733
TI  - Impact of highly active antiretroviral therapy on incidence and management of
      human immunodeficiency virus-related opportunistic infections.
AB  - We review the changes in incidences of HIV-related opportunistic infections and
      the safety of discontinuation of primary and secondary prophylaxis for HIV
      related opportunistic infections in patients achieving immune restoration after
      the introduction of highly active antiretroviral therapy (HAART). HIV-related
      opportunistic infections continue to occur in patients who are newly diagnosed
      with HIV infection, those in the early course of HAART or non-adherent to HIV
      care and HAART, and those in whom non-HIV-related infections have emerged as a
      significant cause of morbidity and mortality in the post-HAART era. Clinical
      studies of patients with tuberculosis and HIV co-infection are reviewed to
      provide appropriate regimen combinations of rifamycins and antiretrovirals, which
      have varying degrees of drug-drug interactions that have posed challenges in the
      management of tuberculosis as well as HIV infection.

PMID- 15456734
TI  - Mutation of amino acids in the alpha 1,3-fucosyltransferase motif affects enzyme
      activity and Km for donor and acceptor substrates.
AB  - Alpha 1,3-fucosyltransferases (FucT) share a conserved amino acid sequence
      designated the alpha 1,3 FucT motif that has been proposed to be important for
      nucleotide sugar binding. To evaluate the importance of the amino acids in this
      motif, each of the alpha 1,3 FucT motif amino acids was replaced with alanine
      (alanine scanning mutagenesis) in human FucT VI, and the resulting mutant
      proteins were analyzed for enzyme activity and kinetically characterized in those
      cases in which the mutant protein had sufficient activity. Two of the mutant
      proteins were inactive, six had less than 1% of wild-type activity, and four had
      approximately 10-50% of wild-type enzyme activity. Three of the mutant proteins
      with significant enzyme activity had substantially larger Km (5 to 15 times) for
      GDP-fucose than FucT VI wild-type enzyme. The fourth mutant protein with
      significant enzyme activity (S249A) had a Km at least 10 times larger than wild
      type FucT VI for the acceptor substrate, with only a slightly larger (2-3 times)
      Km for GDP-fucose. Thus mutation of any of the amino acids within the alpha 1,3
      FucT motif to Ala affects alpha 1,3-FucT activity, and substitution of Ala for
      some of the alpha 1,3 FucT motif amino acids results in proteins with altered
      kinetic constants for both the acceptor and donor substrates. Secondary structure
      prediction suggests a helix-loop-helix fold for the alpha 1,3 FucT motif, which
      can be used to rationalize the effects of mutations in terms of 3D structure.

PMID- 15456735
TI  - A MUC1 tandem repeat reporter protein produced in CHO-K1 cells has sialylated
      core 1 O-glycans and becomes more densely glycosylated if coexpressed with
      polypeptide-GalNAc-T4 transferase.
AB  - A recombinant mucin O-glycosylation reporter protein, containing 1.7 tandem
      repeats (TRs) from the transmembrane mucin MUC1, was constructed. The reporter
      protein, MUC1(1.7TR)-IgG2a, was produced in CHO-K1 cells to study the
      glycosylation of the MUC1 TR and the in vivo role of polypeptide-GalNAc-T4
      glycosyltransferase. N-terminal sequencing of MUC1(1.7TR)-IgG2a showed that all
      five potential O-glycosylation sites within the TR were used, with an average
      density of 4.5 glycans per repeat. The least occupied site was Thr in the PDTR
      motif, where 75% of the molecules were glycosylated, compared to 88-97% at the
      other sites. This glycan density was confirmed by an alternative liquid
      chromatography-mass spectrometry (LC-MS) based approach. The O-linked
      oligosaccharides were released from MUC1(1.7TR)-IgG2a and analyzed by nano-LC-MS
      and LC-MS/MS. Four oligosaccharides were present, NeuAcalpha2-3Galbeta1
      3GalNAcol, NeuAcalpha2-3Galbeta1-3(NeuAcalpha2-6)GalNAcol, Galbeta1-3(NeuAcalpha2
      6)GalNAcol, and Galbeta1-3GalNAcol, the two first being most abundant.
      Coexpression of the human polypeptide-GalNAc-T4 transferase with MUC1(1.7TR)
      IgG2a increased the glycan occupancy at Thr in PDTR, Ser in VTSA, and Ser in
      GSTA, supporting the function of GalNAc-T4 proposed from previous in vitro
      studies. The expression of GalNAc-T4 with a mutation in the first lectin domain
      (alpha) had no glycosylation effect on PDTR and GSTA but surprisingly gave a
      dominant negative effect with a decreased glycosylation to around 50% at the Ser
      in VTSA. The results show that introduction of glycosyltransferases can
      specifically alter the sites for O-glycosylation in vivo.

PMID- 15456736
TI  - Molecular cloning of two Arabidopsis UDP-galactose transporters by
      complementation of a deficient Chinese hamster ovary cell line.
AB  - Nucleotide-sugar transporters (NSTs) form a family of structurally related
      transmembrane proteins that transport nucleotide-sugars from the cytoplasm to the
      endoplasmic reticulum and Golgi lumen. In these organelles, activated sugars are
      substrates for various glycosyltransferases involved in oligo- and polysaccharide
      biosynthesis. The Arabidopsis thaliana genome contains more than 40 members of
      this transporter gene family, of which only a few are functionally characterized.
      In this study, two Arabidopsis UDP-galactose transporter cDNAs (UDP-GalT1 and UDP
      GalT2) are isolated by expression cloning using a Chinese hamster ovary cell line
      (CHO-Lec8) deficient in UDP-galactose transport. The isolated genes show only 21%
      identity to each other and very limited sequence identity with human and yeast
      UDP-galactose transporters and other NSTs. Despite this low overall identity, the
      two proteins clearly belong to the same gene family. Besides complementing Lec8
      cells, the two NSTs are shown to transport exclusively UDP-galactose by an in
      vitro NST assay. The most homologous proteins with known function are plant
      transporters that locate in the inner chloroplast membrane and transport triose
      phosphate, phosphoenolpyruvate, glucose-6-phosphate, and xylulose 5-phosphate.
      Also, the latter proteins are members of the same family, which therefore has
      been named the NST/triose-phosphate transporter family.

PMID- 15456737
TI  - A cutaneous gene therapy approach to treat infection through keratinocyte
      targeted overexpression of antimicrobial peptides.
AB  - Infection represents a major associated problem in severely burned patients, as
      it causes skin graft failure and increases the risk of mortality. Topical and
      systemic antibiotic treatment is limited by the appearance of resistant bacterial
      strains. Antimicrobial peptides (AMPs) are gene-encoded "natural antibiotics"
      that form part of the innate mechanism of defense and may be active against such
      antibiotic-resistant microorganisms. Several microbicidal peptides are expressed
      in human skin under inflammatory conditions, and their function is not only
      limited to microbial killing but also influences tissue repair and adaptive
      immunity. Protein delivery through cutaneous gene therapy is a promising
      therapeutic tool for both skin and nonskin diseases. Here we present a gene
      transfer approach aimed at delivering antimicrobial peptides from keratinocytes.
      Adenoviral vectors encoding antimicrobial peptide genes were used to infect human
      keratinocytes growing either on plastic or as part of cultured skin equivalents.
      Inhibition of bacterial growth occurred both in conditioned media and in direct
      contact with AMPs gene-transduced keratinocytes. In addition, we showed
      cooperative effects after transfer of combinations of genes encoding for AMPs
      with structural differences. Combined cutaneous tissue engineering in conjunction
      with (microbicidal) gene therapy emerges as a tailored therapeutic approach that
      is useful for wound coverage and, in this case, concomitantly combating
      infection.

PMID- 15456738
TI  - Glucocorticoid treatment alleviates dystrophic myofiber pathology by activation
      of the calcineurin/NF-AT pathway.
AB  - Duchenne muscular dystrophy (DMD) is a progressive and ultimately fatal skeletal
      muscle disease. Currently, the most effective therapy is the administration of a
      subclass of glucocorticoids, most notably deflazacort. Although deflazacort
      treatment can attenuate DMD progression, extend ambulation, and maintain muscle
      strength, the mechanism of its action remains unknown. Prior observations have
      shown that activation of a JNK1-mediated signal transduction cascade contributes
      to the progression of the DMD phenotype, in part by phosphorylation and
      inhibition of a calcineurin sensitive NF-ATc1 transcription factor. Here, we
      observed that deflazacort treatment restored myocyte viability in muscle cells
      with constitutive activation of JNK1 and in dystrophic mdx mice. However,
      deflazacort treatment did not alter JNK1 activity itself, but rather led to an
      increase in the activity of the calcineurin phosphatase and an up-regulation of
      NF-ATc1-dependent gene expression. The prophylactic effect of deflazacort
      treatment was associated with increased expression of NF-ATc1 target genes such
      as the dystrophin homologue utrophin. Moreover, the muscle sparing effects of
      deflazacort were completely abolished when used in conjunction with the
      calcineurin inhibitor cyclosporine. Collectively, these results show that
      deflazacort attenuates loss of dystrophic myofiber integrity by up-regulating the
      activity of the phosphatase calcineurin, which in turn negates JNK1 inhibition of
      NF-ATc1-mediated phosphorylation and nuclear exclusion of NF-ATc1.

PMID- 15456739
TI  - Structural basis of endothelial lipase tropism for HDL.
AB  - Lipoprotein lipase (LPL) and endothelial lipase (EL), the most closely related
      enzymes among the members of the triglyceride lipase gene family with regard to
      primary sequence, have distinct lipolytic properties (triglyceride lipase vs.
      phospholipase) as well as different preferences for specific types of
      lipoproteins [triglyceride-rich lipoproteins vs. high density lipoprotein (HDL)]
      Lipid substrate specificity is believed to be conferred by the lid region located
      in the amino-terminal domain of the enzymes, whereas surprisingly little work has
      been done to identify the region mediating lipoprotein substrate specificity. To
      determine the domain responsible for lipoprotein preference within each enzyme,
      we generated the domain chimeric enzyme LPL-EL. The heterologous carboxy-terminal
      (C terminal) domain did not change lipid substrate preference (triglyceride vs.
      phospholipase) as determined by using artificial substrates. The EL C-terminal
      domain, however, enabled LPL-EL to bridge HDL particles like wild-type EL,
      whereas LPL only mediated binding of very low density lipoprotein. Unlike wild
      type LPL, LPL-EL had substantial ability to hydrolyze HDL lipids similar to that
      of wild-type EL. Overexpression of LPL-EL in wild-type mice resulted in
      significantly reduced levels of HDL cholesterol and phospholipids by 93 and 85%,
      respectively, similar to the extent seen in EL-expressing mice, whereas no
      reduction of these parameters was observed in LPL-expressing mice. We conclude
      that the C-terminal domain of EL is crucial for the ability of EL to bind and to
      hydrolyze HDL and converts LPL to an enzyme fully capable of hydrolyzing HDL,
      highlighting the importance of the C-terminal lipase domain in lipoprotein
      substrate preference.

PMID- 15456740
TI  - Oxidative stress and cigarette smoke alter chromatin remodeling but
      differentially regulate NF-kappaB activation and proinflammatory cytokine release
      in alveolar epithelial cells.
AB  - Oxidative stress is implicated in lung inflammation due to its effect on
      proinflammatory gene transcription. Changes in gene transcription depend on
      chromatin remodeling and the relative activities of histone acetyltransferases
      (HATs) and histone deacetylases (HDACs). Alterations in the nuclear histone
      acetylation:deacetylation balance may result in uncontrolled transcription of
      specific proinflammatory genes. We studied the effect of hydrogen peroxide (H2O2)
      and cigarette smoke condensate (CSC) on histone acetylation:deacetylation in
      human alveolar epithelial cells (A549). H2O2 and CSC significantly increased
      acetylation of histone H4 proteins and were associated with decreased HDAC
      activity and HDAC2 levels in A549 cells. Also, the decreased HDAC2 activity was
      due to protein modification by aldehydes and nitric oxide products. Pretreatment
      of A549 cells with N-acetyl-l-cysteine attenuated the oxidant-mediated reduction
      in HDAC activity. Treatment of A549 cells with CSC did not cause nuclear factor
      kappaB (NF-kappaB) activation or expression and release of either interleukin
      (IL)-8 or IL-6. However, H2O2, tumor necrosis factor-alpha (TNF-alpha), and IL
      1beta significantly increased NF-kappaB activation and expression of IL-8
      compared with control cells. Interestingly, CSC dose dependently inhibited TNF
      alpha- and IL-1beta-mediated NF-kappaB activation and IL-8 expression. Thus, H2O2
      and CSC enhance acetylation of histone proteins and decrease histone deacetylase
      activity but differentially regulate proinflammatory cytokine release in alveolar
      epithelial cells.

PMID- 15456741
TI  - Cyclic exposure to hypoxia and reoxygenation selects for tumor cells with defects
      in mitochondrial apoptotic pathways.
AB  - The negative influence of hypoxia on the outcome of malignant tumors may be
      caused by direct oxygen effects, and potentially, the selection of resistant
      tumor cells under repetitive hypoxia. To evaluate whether cyclic hypoxia selects
      for resistant cells and to analyze the underlying mechanisms, the influence of
      cyclic hypoxia on intracellular death pathways was determined in tumor cells. It
      could be demonstrated that cyclic hypoxia selects for cells with increased
      resistance against hypoxia-induced apoptosis. These cells exhibited a cross
      resistance against paradigmatic triggers of mitochondrial apoptotic pathways
      (ionizing radiation/etoposide). In contrast, TRAIL-receptor mediated apoptosis
      remained unaffected. Thus, cyclic hypoxia selects for cells with defects of the
      mitochondrial rather than receptor-mediated pathways. Selection of p53-defective
      cells has been described as a consequence of cyclic hypoxia; therefore, we
      evaluated the impact of hypoxic selection on activation of p21 and downstream
      mediators of p53-dependent apoptosis. p53 function and protein levels of key
      mediators of mitochondrial apoptosis remained unaffected by hypoxic selection.
      However, radiation-induced conformational changes of Bax were reduced after
      cyclic hypoxia. In summary, it could be demonstrated that hypoxic stress confers
      a selection pressure on mitochondrial apoptotic pathways and, consecutively, to
      an increased resistance toward mitochondrial death triggers.

PMID- 15456742
TI  - Transcription profiling analysis of the mechanisms of vaccine-induced protection
      against H. pylori.
AB  - Development of a vaccine against H. pylori is regarded as desirable alternative
      to the current antibiotic therapy regimens. Mice immunized with an attenuated
      recombinant Salmonella typhimurium expressing H. pylori urease subunits A&B have
      dramatically reduced bacterial loads after a single dose. The mechanism(s) of
      protection against this largely extra-cellular pathogen are not fully understood.
      The aim of this study was to identify genes that were regulated specifically in
      response to immunization, in order to gain a broader picture of the immune
      response in the immunized gastric epithelium. Gene expression in RNA isolated
      from the gastric mucosa of immunized and infected Balb/c mice was compared with
      that in infected only mice at 1, 3, and 14 days after challenge with a mouse
      adapted strain of H. pylori. We show that infection with H. pylori causes an
      immediate reaction in vivo, which was clearly divided into acute and chronic
      phases, and further that the transcriptional response in the H. pylori infected
      and immunized gastric mucosa is unique. Analysis of gene expression patterns at
      day 14 post-infection suggested not only the beginning of a lymphocytic
      infiltrate, but of an integrated epithelial response characterized by increased
      expression of genes controlling cell cycle and turnover. This observation was
      confirmed in independent experiments. The global approach has brought new
      insights to the effect of immunization on the gastric epithelium and has led us
      to propose a new multi-factorial model for the mechanisms underlying vaccine
      induced protection.

PMID- 15456743
TI  - Interaction of calcium-bound C-reactive protein with fibronectin is controlled by
      pH: in vivo implications.
AB  - C-reactive protein (CRP) binds with high affinity to fibronectin (Fn), a major
      component of the extracellular matrix (ECM), but at physiological pH the binding
      is inhibited by calcium ions (Ca2+). Because CRP circulates in the blood in Ca2+ 
      bound form, the occurrence of CRP-Fn interactions in vivo has been doubtful. To
      define the basis of inhibition of CRP-Fn interaction by Ca2+ at pH 7.0, we
      hypothesized that Fn-binding site on CRP consisted of amino acids co-ordinating
      Ca2+. Site-directed mutagenesis of amino acids co-ordinating Ca2+ drastically
      decreased the binding of CRP to Fn, indicating that the Ca2+ -binding site indeed
      formed the Fn-binding site. To determine the requirements for possible
      interaction between Ca2+ -bound CRP and Fn, we investigated inhibition of CRP-Fn
      interaction by Ca2+ as a function of pH. Ca2+ did not inhibit binding of CRP to
      Fn at pH 6.5 and lower. The contrasting Fn binding properties of CRP at
      physiological and mildly acidic pH indicated that the interaction of Ca2+ -bound
      CRP with Fn was controlled by pH. We conclude that the inhibition of binding of
      CRP to Fn by Ca2+ at pH 7.0 is a mechanism to prevent CRP-Fn interactions under
      normal conditions. CRP, in its Ca2+ -bound state, is capable of binding Fn but
      only at the inflammatory sites and tumors with low pH. CRP, Fn, and the ECM all
      have been implicated in cancer. Taken together our data raise the possibility
      that CRP-Fn interactions may change the architecture of ECM to modify the
      development of tumors.

PMID- 15456744
TI  - Cdk4 is indispensable for postnatal proliferation of the anterior pituitary.
AB  - For proper development and tissue homeostasis, cell cycle progression is
      controlled by multilayered mechanisms. Recent studies using knock-out mice have
      shown that animals can develop relatively normally with deficiency for each of
      the G1/S-regulatory proteins, D-type and E-type cyclins, cyclin-dependent kinase
      4 (Cdk4), and Cdk2. Although Cdk4-null mice show no embryonic lethality, they
      exhibit specific endocrine phenotypes, i.e. dwarfism, infertility, and diabetes.
      Here we have demonstrated that Cdk4 plays an essential non-redundant role in
      postnatal proliferation of the anterior pituitary. Pituitaries from wild-type and
      Cdk4-null embryos at embryonic day 17.5 are morphologically indistinguishable
      with similar numbers of cells expressing a proliferating marker, Ki67, and cells
      expressing a differentiation marker, growth hormone. In contrast, anterior
      pituitaries of Cdk4-null mice at postnatal 8 weeks are extremely hypoplastic with
      markedly decreased numbers of Ki67+ cells, suggesting impaired cell
      proliferation. Pituitary hyperplasia induced by transgenic expression of human
      growth hormone-releasing hormone (GHRH) is significantly diminished in the Cdk4+/
      genetic background and completely abrogated in the Cdk4-/- background. Small
      interfering RNA (siRNA)-mediated knockdown of Cdk4 inhibits GHRH-induced
      proliferation of GH3 somato/lactotroph cells with restored expression of GHRH
      receptors. Cdk4 siRNA also inhibits estrogen-dependent cell proliferation in GH3
      cells and closely related GH4 cells. In contrast, Cdk6 siRNA does not diminish
      proliferation of these cells. Furthermore, Cdk4 siRNA does not affect GHRH
      induced proliferation of mouse embryonic fibroblasts or estrogen-dependent
      proliferation of mammary carcinoma MCF-7 cells. Taken together, Cdk4 is
      dispensable for prenatal development of the pituitary or proliferation of other
      non-endocrine tissues but indispensable specifically for postnatal proliferation
      of somato/lactotrophs.

PMID- 15456745
TI  - Identification of a novel co-regulator interaction surface on the ligand binding
      domain of Nurr1 using NMR footprinting.
AB  - The nuclear receptor Nurr1 is a transcription factor essential for the
      development of midbrain dopaminergic neurons in vertebrates. Recent crystal
      structures of the Nurr1 ligand binding domain (LBD) and the Drosophila orthologue
      dHR38 revealed that, although these receptors share the classical LBD
      architecture, they lack a ligand binding cavity. This volume is instead filled
      with bulky hydrophobic side chains. Furthermore the "canonical" non-polar co
      regulator binding groove is filled with polar side chains; thus, the regulation
      of transcription by this sub-family of nuclear receptor LBDs may be mediated by
      some other interaction surface on the LBD. We report here the identification of a
      novel co-regulator interface on the LBD of Nurr1. We used an NMR footprinting
      strategy that facilitates the identification of an interaction surface without
      the need of a full assignment. We found that non-polar peptides derived from the
      co-repressors SMRT and NCoR bind to a hydrophobic patch on the LBD of Nurr1. This
      binding surface involves a groove between helices 11 and 12. Mutations in this
      site abolish activation by the Nurr1 LBD. These findings give insight into the
      unique mechanism of action of this class of nuclear receptors.

PMID- 15456746
TI  - Histone H4 hyperacetylation precludes histone H4 lysine 20 trimethylation.
AB  - Posttranslational modification of histones is a common means of regulating
      chromatin structure and thus diverse nuclear processes. Using a hydrophilic
      interaction liquid chromatographic separation method in combination with mass
      spectrometric analysis, the present study investigated the alterations in histone
      H4 methylation/acetylation status and the interplay between H4 methylation and
      acetylation during in vitro differentiation of mouse erythroleukemia cells and
      how these modifications affect the chromatin structure. Independently of the type
      of inducer used (dimethyl sulfoxide, hexamethylenebisacetamide, butyrate, and
      trichostatin A), we observed a strong increase in non- and monoacetylated H4
      lysine 20 (H4-Lys(20)) trimethylation. An increase in H4-Lys(20) trimethylation,
      however, to a clearly lesser extent, was also found when cells accumulated in the
      stationary phase. Since we show that trimethylated H4-Lys(20) is localized to
      heterochromatin, the increase in H4-Lys(20) trimethylation observed indicates an
      accumulation of chromatin-dense and transcriptionally silent regions during
      differentiation and during the accumulation of control cells in the stationary
      phase, respectively. When using the deacetylase inhibitors butyrate or
      trichostatin A, we found that H4 hyperacetylation prevents H4-Lys(20)
      trimethylation, but not mono- or dimethylation, and that the nonacetylated
      unmethylated H4-Lys(20) is therefore the most suitable substrate for H4-Lys(20)
      trimethylase. Summarizing, histone H4-Lys(20) hypotrimethylation correlates with
      H4 hyperacetylation and H4-Lys(20) hypertrimethylation correlates with H4
      hypoacetylation. The results provide a model for how transcriptionally active
      euchromatin might be converted to the compacted, transcriptionally silent
      heterochromatin.

PMID- 15456747
TI  - MBD3L1 is a transcriptional repressor that interacts with methyl-CpG-binding
      protein 2 (MBD2) and components of the NuRD complex.
AB  - Methyl-CpG-binding domain proteins 2 and 3 (MBD2 and MBD3) are transcriptional
      repressors that contain methyl-CpG binding domains and are components of a CpG
      methylated DNA binding complex named MeCP1. Methyl-CpG-binding protein 3-like 1
      (MBD3L1) is a protein with substantial homology to MBD2 and MBD3, but it lacks
      the methyl-CpG binding domain. MBD3L1 interacts with MBD2 and MBD3 in vitro and
      in yeast two-hybrid assays. Gel shift experiments with a CpG-methylated DNA probe
      indicate that recombinant MBD3L1 can supershift an MBD2-methylated DNA complex.
      In vivo, MBD3L1 associates with and colocalizes with MBD2 but not with MBD3 and
      is recruited to 5-methylcytosine-rich pericentromeric heterochromatin in mouse
      cells. In glutathione S-transferase pull-down assays MBD3L1 is found associated
      with several known components of the MeCP1.NuRD complex, including HDAC1, HDAC2,
      MTA2, MBD2, RbAp46, and RbAp48, but MBD3 is not found in the MBD3L1-bound
      fraction. MBD3L1 enhances transcriptional repression of methylated DNA by MBD2.
      The data are consistent with a role of MBD3L1 as a methylation-dependent
      transcriptional repressor that may interchange with MBD3 as an MBD2-interacting
      component of the NuRD complex. MBD3L1 knockout mice were created and were found
      to be viable and fertile, indicating that MBD3L1 may not be essential or there is
      functional redundancy (through MBD3) in this pathway. Overall, this study reveals
      additional complexities in the mechanisms of transcriptional repression by the
      MBD family proteins.

PMID- 15456748
TI  - Synaptotagmin VII is targeted to dense-core vesicles and regulates their Ca2+ 
      dependent exocytosis in PC12 cells.
AB  - It has recently been proposed that synaptotagmin (Syt) VII functions as a plasma
      membrane Ca2+ sensor for dense-core vesicle exocytosis in PC12 cells based on the
      results of transient overexpression studies using green fluorescent protein (GFP)
      tagged Syt VII; however, the precise subcellular localization of Syt VII is still
      a matter of controversy (plasma membrane versus secretory granules). In this
      study we established a PC12 cell line "stably expressing" the Syt VII-GFP
      molecule and demonstrated by immunocytochemical and immunoelectron microscopic
      analyses that the Syt VII-GFP protein is localized on dense-core vesicles as well
      as in other intracellular membranous structures, such as the trans-Golgi network
      and lysosomes. Syt VII-GFP forms a complex with endogenous Syts I and IX, but not
      with Syt IV, and it colocalize well with Syts I and IX in the cellular processes
      (where dense-core vesicles are accumulated) in the PC12 cell line. We further
      demonstrated by an N-terminal antibody-uptake experiment that Syt VII-GFP
      containing dense-core vesicles undergo Ca2+ -dependent exocytosis, the same as
      endogenous Syt IX-containing vesicles. Moreover, silencing of Syt VII-GFP with
      specific small interfering RNA dramatically reduced high KCl-dependent
      neuropeptide Y secretion from the stable PC12 cell line (approximately 60% of the
      control cells), whereas the same small interfering RNA had little effect on
      neuropeptide Y secretion from the wild-type PC12 cells (approximately 85-90% of
      the control cells), indicating that the level of endogenous expression of Syt VII
      molecules must be low. Our results indicate that the targeting of Syt VII-GFP
      molecules to specific membrane compartment(s) is affected by the transfection
      method (transient expression versus stable expression) and suggested that Syt VII
      molecule on dense-core vesicles functions as a vesicular Ca2+ sensor for
      exocytosis in endocrine cells.

PMID- 15456749
TI  - Identification of residues within UvrB that are important for efficient DNA
      binding and damage processing.
AB  - The UvrB protein is the central recognition protein in bacterial nucleotide
      excision repair. We have shown previously that the highly conserved beta-hairpin
      motif in Bacillus caldotenax UvrB is essential for DNA binding, damage
      recognition, and UvrC-mediated incision, as deletion of the upper part of the
      beta-hairpin (residues 97-112) results in the inability of UvrB to be loaded onto
      damaged DNA, defective incision, and the lack of strand-destabilizing activity.
      In this work, we have further examined the role of the beta-hairpin motif of UvrB
      by a mutational analysis of 13 amino acids within or in the vicinity of the beta
      hairpin. These amino acids are predicted to be important for the interaction of
      UvrB with both damaged and non-damaged DNA strands as well as the formation of
      salt bridges between the beta-hairpin and domain 1b of UvrB. The resulting
      mutants were characterized by standard functional assays such as oligonucleotide
      incision, electrophoretic mobility shift, strand-destabilizing, and ATPase
      assays. Our data indicated a direct role of Tyr96, Glu99, and Arg123 in damage
      specific DNA binding. In addition, Tyr93 plays an important but less essential
      role in DNA binding by UvrB. Finally, the formation of salt bridges between the
      beta-hairpin and domain 1b, involving amino acids Lys111 bound to Glu307 and
      Glu99 bound to Arg367 or Arg289, are important but not essential for the function
      of UvrB.

PMID- 15456750
TI  - A polymorphism in thrombospondin-1 associated with familial premature coronary
      artery disease alters Ca2+ binding.
AB  - A single nucleotide polymorphism that results in substitution at residue 700 of a
      serine (Ser-700) for an asparagine (Asn-700) in thrombospondin-1 is associated
      with familial premature coronary artery disease. The polymorphism is located in
      the first of 13 Ca2+ -binding motifs, within a consensus sequence in which Asn
      700 likely coordinates Ca2+. Equilibrium dialysis of constructs comprised of the
      adjoining epidermal growth factor-like module and the Ca2+ -binding region (E3Ca)
      demonstrated that E3Ca Ser-700 binds significantly less Ca2+ than E3Ca Asn-700 at
      low [Ca2+]. The hypothesis that this difference is due to loss of a binding site
      in Ser-700 protein was tested with truncations of E3Ca containing four (Tr4),
      three (Tr3), two (Tr2), or one (Tr1) N-terminal Ca2+ -binding motifs. The Ser-700
      truncation constructs bound 1 fewer Ca2+ than matching Asn-700 constructs and
      exhibited decreased binding affinities. Intrinsic fluorescence of a tryptophan at
      residue 698 (Trp-698) in the most N-terminal motif was cooperatively quenched by
      the addition of Ca2+ to Asn-700 Tr2, Tr3, and Tr4 constructs. In Ser-700
      constructs, quenching of Trp-698 was incomplete in the Tr2 and Tr3 constructs and
      complete only in the Tr4 construct. Ca2+ -induced quenching of Ser-700 constructs
      required higher [Ca2+] and was slower as shown in stopped-flow experiments than
      quenching of Asn-700 constructs. Such differences were not found with Tb3+, which
      quenched the fluorescence of Asn-700 and Ser-700 constructs equivalently. Thus,
      the Ser-700 polymorphism alters a rapidly filled, high affinity Ca2+ -binding
      site in the first Ca2+ -binding motif. Slower Ca2+ binding to adjoining motifs
      partly compensates for the change.

PMID- 15456751
TI  - The peptide-substrate-binding domain of collagen prolyl 4-hydroxylases is a
      tetratricopeptide repeat domain with functional aromatic residues.
AB  - Collagen prolyl 4-hydroxylases catalyze the formation of 4-hydroxyproline in -X
      Pro-Gly-sequences and have an essential role in collagen synthesis. The
      vertebrate enzymes are alpha2beta2 tetramers in which the catalytic alpha
      subunits contain separate peptide-substrate-binding and catalytic domains. We
      report on the crystal structure of the peptide-substrate-binding domain of the
      human type I enzyme refined at 2.3 A resolution. It was found to belong to a
      family of tetratricopeptide repeat domains that are involved in many protein
      protein interactions and consist of five alpha-helices forming two
      tetratricopeptide repeat motifs plus the solvating helix. A prominent feature of
      its concave surface is a deep groove lined by tyrosines, a putative binding site
      for proline-rich Tripeptides. Solvent-exposed side chains of three of the
      tyrosines have a repeat distance similar to that of a poly-L-proline type II
      helix. The aromatic surface ends at one of the tyrosines, where the groove curves
      almost 90 degrees away from the linear arrangement of the three tyrosine side
      chains, possibly inducing a bent conformation in the bound peptide. This finding
      is consistent with previous suggestions by others that a minimal structural
      requirement for proline 4-hydroxylation may be a sequence in the poly-L-proline
      type II conformation followed by a beta-turn in the Pro-Gly segment. Site
      directed mutagenesis indicated that none of the tyrosines was critical for
      tetramer assembly, whereas most of them were critical for the binding of a
      peptide substrate and inhibitor both to the domain and the alpha2beta2 enzyme
      tetramer.

PMID- 15456752
TI  - Modes of caldesmon binding to actin: sites of caldesmon contact and modulation of
      interactions by phosphorylation.
AB  - Smooth muscle caldesmon binds actin and inhibits actomyosin ATPase activity.
      Phosphorylation of caldesmon by extracellular signal-regulated kinase (ERK)
      reverses this inhibitory effect and weakens actin binding. To better understand
      this function, we have examined the phosphorylation-dependent contact sites of
      caldesmon on actin by low dose electron microscopy and three-dimensional
      reconstruction of actin filaments decorated with a C-terminal fragment, hH32K, of
      human caldesmon containing the principal actin-binding domains. Helical
      reconstruction of negatively stained filaments demonstrated that hH32K is located
      on the inner portion of actin subdomain 1, traversing its upper surface toward
      the C-terminal segment of actin, and forms a bridge to the neighboring actin
      monomer of the adjacent long pitch helical strand by connecting to its subdomain
      3. Such lateral binding was supported by cross-linking experiments using a mutant
      isoform, which was capable of cross-linking actin subunits. Upon ERK
      phosphorylation, however, the mutant no longer cross-linked actin to polymers.
      Three-dimensional reconstruction of ERK-phosphorylated hH32K indeed indicated
      loss of the interstrand connectivity. These results, together with fluorescence
      quenching data, are consistent with a phosphorylation-dependent conformational
      change that moves the C-terminal end segment of caldesmon near the
      phosphorylation site but not the upstream region around Cys(595), away from F
      actin, thus neutralizing its inhibitory effect on actomyosin interactions. The
      binding pattern of hH32K suggests a mechanism by which unphosphorylated, but not
      ERK-phosphorylated, caldesmon could stabilize actin filaments and resist F-actin
      severing or depolymerization in both smooth muscle and nonmuscle cells.

PMID- 15456753
TI  - Nuclear monothiol glutaredoxins of Saccharomyces cerevisiae can function as
      mitochondrial glutaredoxins.
AB  - Glutaredoxins are thiol oxidoreductases that regulate protein redox state. In
      Saccharomyces cerevisiae, Grx1 and Grx2 are cytosolic dithiol glutaredoxins,
      whereas Grx3, Grx4, and Grx5 are monothiol glutaredoxins. Grx5 locates at the
      mitochondrial matrix and is needed for iron/sulfur cluster biogenesis. Its
      absence causes phenotypes such as inactivation of iron/sulfur enzymes and
      sensitivity to oxidative stress. Whereas Grx5 contains a single glutaredoxin
      domain, in Grx3 and Grx4 a thioredoxin-like domain is fused to the glutaredoxin
      domain. Here we have shown that Grx3 locates at the nucleus and that the
      thioredoxin-like domain is required for such location. We have addressed the
      functional divergence among glutaredoxins by targeting Grx2/3/4 molecules to the
      mitochondrial matrix using the Grx5 targeting sequence. The mitochondrial forms
      of Grx3 and Grx4 partially rescue the defects of a grx5 null mutant. On the
      contrary, mitochondrially targeted Grx2 does not suppress the mutant phenotype.
      Both the thioredoxin-like and glutaredoxin domains are needed for the
      mitochondrial activity of Grx3, although none of the cysteine residues at the
      thioredoxin-like domain is required for rescue of the grx5 phenotypes. We have
      concluded that dithiol glutaredoxins are functionally divergent from monothiol
      ones, but the latter can interchange their biological activities when compartment
      barriers are surpassed.

PMID- 15456754
TI  - Two distinct tyrosine-based motifs enable the inhibitory receptor FcgammaRIIB to
      cooperatively recruit the inositol phosphatases SHIP1/2 and the adapters
      Grb2/Grap.
AB  - FcgammaRIIB are low-affinity receptors for IgG that contain an immunoreceptor
      tyrosine-based inhibition motif (ITIM) and inhibit immunoreceptor tyrosine-based
      activation motif (ITAM)-dependent cell activation. When coaggregated with ITAM
      bearing receptors, FcgammaRIIB become tyrosyl-phosphorylated and recruit the Src
      homology 2 (SH2) domain-containing inositol 5'-phosphatases SHIP1 and SHIP2,
      which mediate inhibition. The FcgammaRIIB ITIM was proposed to be necessary and
      sufficient for recruiting SHIP1/2. We show here that a second tyrosine-containing
      motif in the intracytoplasmic domain of FcgammaRIIB is required for SHIP1/2 to be
      coprecipitated with the receptor. This motif functions as a docking site for the
      SH2 domain-containing adapters Grb2 and Grap. These adapters interact via their C
      terminal SH3 domain with SHIP1/2 to form a stable receptor-phosphatase-adapter
      trimolecular complex. Both Grb2 and Grap are required for an optimal
      coprecipitation of SHIP with FcgammaRIIB, but one adapter is sufficient for the
      phosphatase to coprecipitate in a detectable manner with the receptors. In
      addition to facilitating the recruitment of SHIPs, the second tyrosine-based
      motif may confer upon FcgammaRIIB the properties of scaffold proteins capable of
      altering the composition and stability of the signaling complexes generated
      following receptor engagement.

PMID- 15456755
TI  - Physical association between the adipocyte fatty acid-binding protein and hormone
      sensitive lipase: a fluorescence resonance energy transfer analysis.
AB  - Previous in vitro studies have established that hormone sensitive lipase (HSL)
      and adipocyte fatty acid-binding protein (AFABP) form a physical complex that
      presumably positions the FABP to accept a product fatty acid generated during
      catalysis. To assess AFABP-HSL interaction within a cellular context, we have
      used lipocytes derived from 293 cells (C8PA cells) and examined physical
      association using fluorescence resonance energy transfer. Transfection of C8PA
      cells with cyan fluorescent protein (CFP)-HSL, yellow fluorescent protein (YFP)
      adipocyte FABP, or YFP-liver FABP revealed that under basal conditions each
      protein was cytoplasmic. In the presence of 20 microm forskolin, CFP-HSL
      translocated to the triacylglycerol droplet, coincident with BODIPY-FA labeled
      depots. Fluorescence resonance energy transfer analysis demonstrated that CFP-HSL
      associated with YFP-adipocyte FABP in both basal and forskolin-treated cells. In
      contrast, little if any fluorescence resonance energy transfer could be detected
      between CFP-HSL and YFP-liver FABP. These results suggest that a pre-lipolysis
      complex containing at least AFABP and HSL exists and that the complex
      translocates to the surface of the lipid droplet.

PMID- 15456756
TI  - Vav1 and vav3 have critical but redundant roles in mediating platelet activation
      by collagen.
AB  - Vav family proteins are guanine nucleotide exchange factors for the Rho/Rac
      family of small GTP-binding proteins. In addition, they have domains that mediate
      protein-protein interactions, including one Src homology 2 (SH2) and two Src
      homology 3 (SH3) domains. Vav1, Vav2, and Vav3 play a crucial role in the
      regulation of phospholipase C gamma (PLC gamma) isoforms by immuno-tyrosine-based
      activation motif (ITAM)-coupled receptors, including the T- and B-cell antigen
      receptors. We have reported in platelets, however, that Vav1 and Vav2 are not
      required for activation of PLC gamma 2 in response to stimulation of the ITAM
      coupled collagen receptor glycoprotein VI (GPVI). Here we report that Vav3 is
      tyrosinephosphorylated upon activation of GPVI but that Vav3-deficient platelets
      also exhibit a normal response upon activation of the ITAM receptor. In sharp
      contrast, platelets deficient in both Vav1 and Vav3 show a marked inhibition of
      aggregation and spreading upon activation of GPVI, which is associated with a
      reduction in tyrosine phosphorylation of PLC gamma 2. The phenotype of Vav1/2/3
      triple-deficient platelets is similar to that of Vav1/3 double-deficient cells.
      These results demonstrate that Vav3 and Vav1 play crucial but redundant roles in
      the activation of PLC gamma 2 by GPVI. This is the first time that absolute
      redundancy between two protein isoforms has been observed with respect to the
      regulation of PLC gamma 2 in platelets.

PMID- 15456757
TI  - The active site of a lon protease from Methanococcus jannaschii distinctly
      differs from the canonical catalytic Dyad of Lon proteases.
AB  - ATP-dependent Lon proteases catalyze the degradation of various regulatory
      proteins and abnormal proteins within cells. Methanococcus jannaschii Lon (Mj
      Lon) is a homologue of Escherichia coli Lon (Ec-Lon) but has two transmembrane
      helices within its N-terminal ATPase domain. We solved the crystal structure of
      the proteolytic domain of Mj-Lon using multiwavelength anomalous dispersion,
      refining it to 1.9-angstroms resolution. The structure displays an overall fold
      conserved in the proteolytic domain of Ec-Lon; however, the active site shows
      uniquely configured catalytic Ser-Lys-Asp residues that are not seen in Ec-Lon,
      which contains a catalytic dyad. In Mj-Lon, the C-terminal half of the beta4
      alpha2 segment is an alpha-helix, whereas it is a beta-strand in Ec-Lon.
      Consequently, the configurations of the active sites differ due to the formation
      of a salt bridge between Asp-547 and Lys-593 in Mj-Lon. Moreover, unlike Ec-Lon,
      Mj-Lon has a buried cavity in the region of the active site containing three
      water molecules, one of which is hydrogen-bonded to catalytic Ser-550. The
      geometry and environment of the active site residues in Mj-Lon suggest that the
      charged Lys-593 assists in lowering the pK(a) of the Ser-550 hydroxyl group via
      its electrostatic potential, and the water in the cavity acts as a proton
      acceptor during catalysis. Extensive sequence alignment and comparison of the
      structures of the proteolytic domains clearly indicate that Lon proteases can be
      classified into two groups depending on active site configuration and the
      presence of DGPSA or (D/E)GDSA consensus sequences, as represented by Ec-Lon and
      Mj-Lon.

PMID- 15456758
TI  - Anti-apoptotic actions of the platelet-activating factor acetylhydrolase I alpha2
      catalytic subunit.
AB  - Platelet-activating factor (PAF) is an important mediator of cell loss following
      diverse pathophysiological challenges, but the manner in which PAF transduces
      death is not clear. Both PAF receptor-dependent and -independent pathways are
      implicated. In this study, we show that extracellular PAF can be internalized
      through PAF receptor-independent mechanisms and can initiate caspase-3-dependent
      apoptosis when cytosolic concentrations are elevated by approximately 15 pM/cell
      for 60 min. Reducing cytosolic PAF to less than 10 pM/cell terminates apoptotic
      signaling. By pharmacological inhibition of PAF acetylhydrolase I and II (PAF-AH)
      activity and down-regulation of PAF-AH I catalytic subunits by RNA interference,
      we show that the PAF receptor-independent death pathway is regulated by PAF-AH I
      and, to a lesser extent, by PAF-AH II. Moreover, the anti-apoptotic actions of
      PAF-AH I are subunit-specific. PAF-AH I alpha1 regulates intracellular PAF
      concentrations under normal physiological conditions, but expression is not
      sufficient to reduce an acute rise in intracellular PAF levels. PAF-AH I alpha2
      expression is induced when cells are deprived of serum or exposed to apoptogenic
      PAF concentrations limiting the duration of pathological cytosolic PAF
      accumulation. To block PAF receptor-independent death pathway, we screened a
      panel of PAF antagonists (CV-3988, CV-6209, BN 52021, and FR 49175). BN 52021 and
      FR 49175 accelerated PAF hydrolysis and inhibited PAF-mediated caspase 3
      activation. Both antagonists act indirectly to promote PAF-AH I alpha2 homodimer
      activity by reducing PAF-AH I alpha1 expression. These findings identify PAF-AH I
      alpha2 as a potent anti-apoptotic protein and describe a new means of
      pharmacologically targeting PAF-AH I to inhibit PAF-mediated cell death.

PMID- 15456759
TI  - Human PTIP facilitates ATM-mediated activation of p53 and promotes cellular
      resistance to ionizing radiation.
AB  - Mus musculus Pax2 transactivation domain-interacting protein (Ptip) is an
      essential gene required for the maintenance of genome stability, although its
      precise molecular role is unclear. Human PTIP (hPTIP) was recently isolated in a
      screen for proteins, translated from cDNA pools, capable of interacting with
      peptides phosphorylated by the ATM (ataxia telangiectasia-mutated)/ATR (ataxia
      telangiectasia-related) protein kinases. hPTIP was described as a 757-amino acid
      protein bearing four BRCT domains. Here we report that instead full-length
      endogenous hPTIP contains 1069 amino acids and six BRCT domains. hPTIP shows
      increased association with 53BP1 in response to ionizing radiation (IR) but not
      in response to other DNA-damaging agents. Whereas translocation of both 53BP1 and
      hPTIP to sites of IR-induced DNA damage occurs independently of ATM, IR-induced
      association of PTIP and 53BP1 requires ATM. Deletion analysis identified the
      domains of 53BP1 and hPTIP required for protein-protein interaction and focus
      formation. Data characterizing the cellular roles of hPTIP are also presented.
      Small interfering RNA was used to show that hPTIP is required for ATM-mediated
      phosphorylation of p53 at Ser(15) and for IR-induced up-regulation of the cyclin
      dependent kinase inhibitor p21. Lowering hPTIP levels also increased cellular
      sensitivity to IR, suggesting that this protein plays a critical role in
      maintaining genome stability.

PMID- 15456760
TI  - Sequences downstream of the erythroid promoter are required for high level
      expression of the human alpha-spectrin gene.
AB  - Alpha-spectrin is a membrane protein critical for the flexibility and stability
      of the erythrocyte. We are attempting to identify and characterize the molecular
      mechanisms controlling the erythroid-specific expression of the alpha-spectrin
      gene. Previously, we demonstrated that the core promoter of the human alpha
      spectrin gene directed low levels of erythroid-specific expression only in the
      early stages of erythroid differentiation. We have now identified a region 3' of
      the core promoter that contains a DNase I hypersensitive site and directs high
      level, erythroid-specific expression in reporter gene/transfection assays. In
      vitro DNase I footprinting and electrophoretic mobility shift assays identified
      two functional GATA-1 sites in this region. Both GATA-1 sites were required for
      full activity, suggesting that elements binding to each site interact in a
      combinatorial manner. This region did not demonstrate enhancer activity in any
      orientation or position relative to either the alpha-spectrin core promoter or
      the thymidine kinase promoter in reporter gene assays. In vivo studies using
      chromatin immunoprecipitation assays demonstrated hyperacetylation of this region
      and occupancy by GATA-1 and CBP (cAMP-response element-binding protein (CREB)
      binding protein). These results demonstrate that a region 3' of the alpha
      spectrin core promoter contains a GATA-1-dependent positive regulatory element
      that is required in its proper genomic orientation. This is an excellent
      candidate region for mutations associated with decreased alpha-spectrin gene
      expression in patients with hereditary spherocytosis and hereditary
      pyropoikilocytosis.

PMID- 15456761
TI  - Mutations in the DNA-binding domain of the transcription factor Bright act as
      dominant negative proteins and interfere with immunoglobulin transactivation.
AB  - Bright, for B cell regulator of immunoglobulin heavy chain transcription, binds
      A+T-rich sequences in the intronic enhancer regions of the murine heavy chain
      locus and 5'-flanking sequences of some variable heavy chain promoters. Most
      resting B cells do not express Bright; however, it is induced after stimulation
      with antigen or polyclonal mitogens. Bright activation results in up-regulation
      of mu transcription; however, it is not clear whether Bright function is critical
      for normal B cell development. To begin to address Bright function during B cell
      development, seven mutated forms of Bright were produced. Five of the seven
      mutants revealed little or no DNA binding activity. Furthermore, because Bright
      binds DNA as a dimer, two of the mutants formed complexes with wild type Bright
      and acted in a dominant negative fashion. Dominant negative Bright prevented the
      up-regulation of mu transcription in transfected Chinese hamster ovary cells
      transfected with wild type Bright. These data identify regions within Bright that
      are required for the DNA binding activity of Bright and for its function as a
      transcription factor.

PMID- 15456762
TI  - Epidermal growth factor receptor-deficient mice have delayed primary endochondral
      ossification because of defective osteoclast recruitment.
AB  - The epidermal growth factor receptor (EGFR) and its ligands function in diverse
      cellular functions including cell proliferation, differentiation, motility, and
      survival. EGFR signaling is important for the development of many tissues,
      including skin, lungs, intestines, and the craniofacial skeleton. We have now
      determined the role of EGFR signaling in endochondral ossification. We analyzed
      long bone development in EGFR-deficient mice. EGFR deficiency caused delayed
      primary ossification of the cartilage anlage and delayed osteoclast and
      osteoblast recruitment. Ossification of the growth plates was also abnormal
      resulting in an expanded area of growth plate hypertrophic cartilage and few bony
      trabeculae. The delayed osteoclast recruitment was not because of inadequate
      expression of matrix metalloproteinases, including matrix metalloproteinase-9,
      which have previously been shown to be important for osteoclast recruitment. EGFR
      was expressed by osteoclasts, suggesting that EGFR ligands may act directly to
      affect the formation and/or function of these cells. EGFR signaling regulated
      osteoclast formation. Inhibition of EGFR tyrosine kinase activity decreased the
      generation of osteoclasts from cultured bone marrow cells.

PMID- 15456763
TI  - Germ cell nuclear factor relieves cAMP-response element modulator tau-mediated
      activation of the testis-specific promoter of human mitochondrial glycerol-3
      phosphate dehydrogenase.
AB  - Mitochondrial glycerol-3-phosphate dehydrogenase (mGPDH) is an essential
      component of the glycerol phosphate shuttle that transfers reduction equivalents
      from the cytosol into the mitochondrion. Within the testis, immunohistological
      analysis localized human mGPDH to late spermatids and to the midpiece of
      spermatozoa. The expression of human mGPDH is regulated by two somatic promoters,
      and here, we describe a third testis-specific promoter of human mGPDH. The usage
      of this testis-specific promoter correlates with the expression of a shortened
      mGPDH transcript of approximately 2.4 kb in length, which is solely detectable
      from testicular RNA. Within the testis-specific promoter, we detected a cAMP
      response element (CRE) site at -51, which binds the testis-specific
      transcriptional activator CRE modulator tau (CREMtau) in electrophoretic mobility
      shift assays. This recognition site overlaps with a nuclear receptor binding half
      site at -49, which binds the testis-specific transcriptional repressor germ cell
      nuclear factor (GCNF). Both factors compete for binding to the same DNA response
      element. Ectopic expression of CREMtau in HepG2 cells activated a promoter-driven
      luciferase construct in transient transfection experiments. Additional
      cotransfection of GCNF relieved this activity, suggesting a down-regulation of
      CREMtau-mediated activation by GCNF. This effect was preserved by introducing the
      CRE/nuclear receptor-binding element into a heterologous promoter context. Our
      data suggest a down-regulation of CREMtau-mediated gene expression by GCNF, which
      might be a general regulation mechanism for several postmeiotically expressed
      genes with a temporal expression peak during early spermatid development.

PMID- 15456764
TI  - Nicastrin, presenilin, APH-1, and PEN-2 form active gamma-secretase complexes in
      mitochondria.
AB  - Mitochondria are central in the regulation of cell death. Apart from providing
      the cell with ATP, mitochondria also harbor several death factors that are
      released upon apoptotic stimuli. Alterations in mitochondrial functions,
      increased oxidative stress, and neurons dying by apoptosis have been detected in
      Alzheimer's disease patients. These findings suggest that mitochondria may
      trigger the abnormal onset of neuronal cell death in Alzheimer's disease. We
      previously reported that presenilin 1 (PS1), which is often mutated in familial
      forms of Alzheimer's disease, is located in mitochondria and hypothesized that
      presenilin mutations may sensitize cells to apoptotic stimuli at the
      mitochondrial level. Presenilin forms an active gamma-secretase complex together
      with Nicastrin (NCT), APH-1, and PEN-2, which among other substrates cleaves the
      beta-amyloid precursor protein (beta-APP) generating the amyloid beta-peptide and
      the beta-APP intracellular domain. Here we have identified dual targeting
      sequences (for endoplasmic reticulum and mitochondria) in NCT and showed
      expression of NCT in mitochondria by immunoelectron microscopy. We also showed
      that NCT together with APH-1, PEN-2, and PS1 form a high molecular weight complex
      located in mitochondria. gamma-secretase activity in isolated mitochondria was
      demonstrated using C83 (alpha-secretase-cleaved C-terminal 83-residue beta-APP
      fragment from BD8 cells lacking presenilin and thus gamma-secretase activity) or
      recombinant C100-Flag (C-terminal 100-residue beta-APP fragment) as substrates.
      Both systems generated an APP intracellular domain, and the activity was
      inhibited by the gamma-secretase inhibitors l-685,458 or Compound E. This novel
      localization of NCT, PS1, APH-1, and PEN-2 expands the role and importance of
      gamma-secretase activity to mitochondria.

PMID- 15456765
TI  - Plants express a lipid transfer protein with high similarity to mammalian sterol
      carrier protein-2.
AB  - This is the first report describing the cloning and characterization of sterol
      carrier protein-2 (SCP-2) from plants. Arabidopsis thaliana SCP-2 (AtSCP-2)
      consists of 123 amino acids with a molecular mass of 13.6 kDa. AtSCP-2 shows 35%
      identity and 56% similarity to the human SCP-2-like domain present in the human D
      bifunctional protein (DBP) and 30% identity and 54% similarity to the human SCP-2
      encoded by SCP-X. The presented structural models of apo-AtSCP-2 and the ligand
      bound conformation of AtSCP-2 reveal remarkable similarity with two of the
      structurally known SCP-2s, the SCP-2-like domain of human DBP and the rabbit SCP
      2, correspondingly. The AtSCP-2 models in both forms have a similar hydrophobic
      ligand-binding tunnel, which is extremely suitable for lipid binding. AtSCP-2
      showed in vitro transfer activity of BODIPY-phosphatidylcholine (BODIPY-PC) from
      donor membranes to acceptor membranes. The transfer of BODIPY-PC was almost
      completely inhibited after addition of 1-palmitoyl 2-oleoyl phosphatidylcholine
      or ergosterol. Dimyristoyl phosphatidic acid, stigmasterol, steryl glucoside, and
      cholesterol showed a moderate to marginal ability to lower the BODIPY-PC transfer
      rate, and the single chain palmitic acid and stearoyl-coenzyme A did not affect
      transfer at all. Expression analysis showed that AtSCP-2 mRNA is accumulating in
      most plant tissues. Plasmids carrying fusion genes between green fluorescent
      protein and AtSCP-2 were transformed with particle bombardment to onion epidermal
      cells. The results from analyzing the transformants indicate that AtSCP-2 is
      localized to peroxisomes.

PMID- 15456766
TI  - An Escherichia coli MutY mutant without the six-helix barrel domain is a dimer in
      solution and assembles cooperatively into multisubunit complexes with DNA.
AB  - Escherichia coli MutY is an adenine and weak guanine DNA glycosylase involved in
      reducing the mutagenic effects of 7,8-dihydro-8-oxoguanine (GO). MutY contains
      three structural domains: an iron-sulfur module, a six-helix barrel module with
      the helix-hairpin-helix motif, and a C-terminal domain. Here, we demonstrate that
      the mutant MutY(Delta26-134), which lacks the six-helix barrel domain, cannot
      complement the mutator phenotype of a mutY mutant in vivo. However, the mutant
      can still bind DNA and has weak catalytic activity at high enzyme concentrations.
      The mutant is a dimer in solution and assembled into two and multiple (up to
      five) complexes with 20- and 44-bp DNA fragments, respectively, in a
      concentration-dependent manner. Higher order complexes with DNA substrates
      containing A/GO mismatches were formed at lower protein concentrations than with
      the A/G mismatch and homoduplex DNA. Measurement of equilibrium binding using
      fluorescence anisotropy showed that the mutant protein retains some specificity
      for A/GO-containing DNA substrates and that the binding event is highly
      cooperative. This is consistent with the MutY structure determined, which
      indicates that GO specificity is contributed by both the six-helix barrel and C
      terminal domains. The nonspecific binding of MutY(Delta26-134) to DNA suggests a
      model in which the specific binding of mismatched DNA by MutY involves sequential
      interactions, in which one MutY molecule scans the DNA and enhances binding of
      another MutY molecule to the A/GO mismatch.

PMID- 15456767
TI  - ERK1/2 controls Na,K-ATPase activity and transepithelial sodium transport in the
      principal cell of the cortical collecting duct of the mouse kidney.
AB  - The collecting duct of normal kidney exhibits significant activity of the MEK1/2
      ERK1/2 pathway as shown in vivo by immunostaining of phosphorylated active ERK1/2
      (pERK1/2). The MEK1/2-ERK1/2 pathway controls many different ion transports both
      in proximal and distal nephron, raising the question of whether this pathway is
      involved in the basal and/or hormone-dependent transepithelial sodium
      reabsorption in the principal cell of the cortical collecting duct (CCD), a
      process mediated by the apical epithelial sodium channel and the basolateral
      sodium pump (Na,K-ATPase). To answer this question we used ex vivo microdissected
      CCDs from normal mouse kidney or in vitro cultured mpkCCDcl4 principal cells.
      Significant basal levels of pERK1/2 were observed ex vivo and in vitro.
      Aldosterone and vasopressin, known to up-regulate sodium reabsorption in CCDs,
      did not change ERK1/2 activity either ex vivo or in vitro. Basal and aldosterone-
      or vasopressin-stimulated sodium transport was down-regulated by the MEK1/2
      inhibitor PD98059, in parallel with a decrease in pERK1/2 in vitro. The activity
      of Na,K-ATPase but not that of epithelial sodium channel was inhibited by MEK1/2
      inhibitors in both unstimulated and aldosterone- or vasopressin-stimulated CCDs
      in vitro. Cell surface biotinylation showed that intrinsic activity rather than
      cell surface expression of Na,K-ATPase was controlled by pERK1/2. PD98059 also
      significantly inhibited the activity of Na,K-ATPase ex vivo. Our data demonstrate
      that the ERK1/2 pathway controls Na,K-ATPase activity and transepithelial sodium
      transport in the principal cell and indicate that basal constitutive activity of
      the ERK1/2 pathway is a critical component of this control.

PMID- 15456768
TI  - Identification and biochemical characterization of two novel collagen binding
      MSCRAMMs of Bacillus anthracis.
AB  - Cell wall-anchored proteins play critical roles in the pathogenesis of infections
      caused by Gram-positive bacteria. Through the analysis of the genome of Bacillus
      anthracis Ames strain, we identified two novel putative cell wall-anchored
      proteins, BA0871 and BA5258, which have sequence homology to CNA, a cell wall
      anchored collagen adhesin of Staphylococcus aureus. The two proteins have similar
      domain organization to that of CNA, with typical signal peptide sequences, a non
      repetitive A region followed by repeats, and a characteristic cell wall-anchoring
      region. They are expressed on the surface of B. anthracis. The A regions of the
      two proteins were predicted to adopt similar structural folds as CNA. Circular
      dichroism analysis of the recombinant A regions of the two proteins (rBA0871A and
      rBA5258A) indicate that their secondary structure compositions are similar to
      those of the A regions of CNA and other cell wall-anchored adhesins. We
      demonstrate through solid phase binding assays and surface plasmon resonance
      analyses that rBA0871A and rBA5258A specifically bound type I collagen in a dose
      dependent and saturable manner. Their dissociation constants (KD) for collagen
      are 1.6-3.2 microm for rBA0871A and 0.6-0.9 microm for rBA5258A, respectively. We
      further demonstrate that BA0871 and BA5258 can mediate cell attachment to
      collagen when expressed on the surface of a heterologous host bacterium. To our
      knowledge these are the first two adhesins of B. anthracis described, which may
      have important implications for our understanding of the pathogenic mechanisms
      explored by this organism.

PMID- 15456769
TI  - SOX9-dependent and -independent transcriptional regulation of human cartilage
      link protein.
AB  - Cartilage link protein is a key component of the cartilage extracellular matrix.
      The transcriptional regulation of the gene encoding cartilage link protein
      (CRTL1) is largely unknown, however. Here, we investigated the regulation of
      CRTL1 by SOX9, a key regulator of cartilage matrix genes and chondrogenesis.
      Knockdown of SOX9 resulted in decreased CRTL1 expression. SOX9 induced CRTL1
      expression effectively in human non-chondrocytic immortalized cell lines as well
      as in mesenchymal stem cell and adult dermal fibroblast. These results indicate
      that, like other cartilage matrix genes, SOX9 is a key regulator of CRTL1. Unlike
      other cartilage matrix genes, however, the activation of CRTL1 by SOX9 and its
      known transcriptional co-activators L-SOX5 and SOX6 was cell type-dependent. Two
      cis-acting enhancer elements resided in the 5'-untranslated region of CRTL1. One
      contained a heptameric SOX binding sequence and showed SOX9-dependent enhancer
      activity in several cell lines. The other showed cell type-specific SOX9
      independent enhancer activity. These findings suggest that the enhancer elements
      may mediate differential expression of CRTL1 during chondrocyte differentiation
      and maturation.

PMID- 15456770
TI  - The transcriptional corepressor, PELP1, recruits HDAC2 and masks histones using
      two separate domains.
AB  - PELP1 (proline-, glutamic acid-, and leucine-rich protein 1) has been recognized
      as a coactivator of estrogen receptor (ER)-recruiting p300/CREB-binding protein
      histone acetyltransferase to the target chromosome. The present study shows that
      PELP1 does indeed coactivate ER-mediated transcription but also serves as a
      corepressor of other nuclear hormone receptors (NR)- and non-NR sequence-specific
      transcription factors tested, including GR, Nur77, AP1, NF-kappaB, and TCF/SRF.
      PELP1 expression also retarded the proliferation of mouse fibroblast cell lines
      in which there was no detectable ER. This was due, at least in part, to the
      suppressed activation of serum-response genes such as c-fos that in turn resulted
      from the blocked histone hyperacetylation of nucleosomes containing the c-fos
      promoter region. The N-terminal leucine-abundant region of PELP1 was observed to
      interact with HDAC2 and exhibited repressive activity when tethered to the
      chromatin. In addition, the C-terminal glutamic acid-abundant region bound to the
      hypoacetylated histones H3 and H4 and prevented them from becoming substrates of
      histone acetyltransferase. Thus PELP1 promotes and maintains the hypoacetylated
      state of histones at the target genomic site, and ER binding reverses its role to
      hyperacetylate histones through an as yet unidentified mechanism.

PMID- 15456771
TI  - Matrix GLA protein stimulates VEGF expression through increased transforming
      growth factor-beta1 activity in endothelial cells.
AB  - Matrix GLA protein (MGP) is expressed in endothelial cells (EC), and MGP
      deficiency results in developmental defects suggesting involvement in EC
      function. To determine the role of MGP in EC, we cultured bovine aortic EC with
      increasing concentrations of human MGP (hMGP) for 24 h. The results showed
      increased proliferation, migration, tube formation, and increased release of
      vascular endothelial growth factor-A (VEGF-A) and basic fibroblast growth factor
      (bFGF). HMGP, added endogenously or transiently expressed, increased VEGF gene
      expression dose-dependently as determined by real-time PCR. To determine the
      mechanism by which hMGP increased VEGF expression, we studied the effect of MGP
      on the activity of transforming growth factor (TGF)-beta1 compared with that of
      bone morphogenetic protein (BMP)-2 using transfection assays with TGF-beta- and
      BMP-response element reporter genes. Our results showed a strong enhancement of
      TGF-beta1 activity by hMGP, which was paralleled by increased VEGF expression.
      BMP-2 activity, on the other hand, was inhibited by hMGP. Neutralizing antibodies
      to TGF-beta blocked the effect of MGP on VEGF expression. The enhanced TGF-beta1
      activity specifically activated the Smad1/5 pathway indicating that the TGF-beta
      receptor activin-like kinase 1 (ALK1) had been stimulated. It occurred without
      changes in expression of TGF-beta1 or ALK1 and was mimicked by transfection of
      constitutively active ALK1, which increased VEGF expression. Expression of VEGF
      and MGP was induced by TGF-beta1, but the induction of MGP preceded that of VEGF,
      consistent with a promoting effect on VEGF expression. Together, the results
      suggest that MGP plays a role in EC function, altering the response to TGF-beta
      superfamily growth factors.

PMID- 15456772
TI  - Paradoxical regulation of biotin utilization in brain and liver and implications
      for inherited multiple carboxylase deficiency.
AB  - Holocarboxylase synthetase (HCS) catalyzes the biotinylation of five carboxylases
      in human cells, and mutations of HCS cause multiple carboxylase deficiency (MCD).
      Although HCS also participates in the regulation of its own mRNA levels, the
      relevance of this mechanism to normal metabolism or to the MCD phenotype is not
      known. In this study, we show that mRNA levels of enzymes involved in biotin
      utilization, including HCS, are down-regulated during biotin deficiency in liver
      while remaining constitutively expressed in brain. We propose that this mechanism
      of regulation is aimed at sparing the essential function of biotin in the brain
      at the expense of organs such as liver and kidney during biotin deprivation. In
      MCD, it is possible that some of the manifestations of the disease may be
      associated with down-regulation of biotin utilization in liver because of the
      impaired activity of HCS and that high dose biotin therapy may in part be
      important to overcoming the adverse regulatory impact in such organs.

PMID- 15456773
TI  - Processive utilization of the human telomerase template: lack of a requirement
      for template switching.
AB  - The ribonucleoprotein telomerase is a specialized reverse transcriptase minimally
      composed of an RNA, TER, and a protein catalytic subunit, TERT. The TER and TERT
      subunits of telomerase associate to form a dimeric enzyme in several organisms,
      including human. A small portion of TER, the template domain, is used by
      telomerase for the synthesis of tandem repeats of telomeric DNA. We studied some
      of the requirements for processive template usage by human telomerase. A blunt
      ended duplex DNA primer was not utilized by telomerase. With a duplex telomeric
      DNA primer, a single-stranded 3' overhang with a minimum length of approximately
      6 bases was required for efficient priming activity. Large substitutions in the
      human TER templating domain did not abolish enzymatic activity, although
      insertion of two residues into this sequence reduced processivity, as did a
      template mutation that results in a mismatch between the template region used for
      copying DNA and the region used for alignment of the substrate primer. Finally,
      by using a complementary pair of catalytically inactive telomerase RNA pseudoknot
      mutants in combination with a marked template, we demonstrated that processive
      synthesis by an obligatory dimer of human telomerase does not require template
      switching. These results indicate that processive template usage by human
      telomerase, like that of Tetrahymena telomerase, is strongly dependent on the
      base identities in the template domain and that a dimeric human telomerase can
      processively utilize a single template.

PMID- 15456774
TI  - The integrin alpha L beta 2 hybrid domain serves as a link for the propagation of
      activation signal from its stalk regions to the I-like domain.
AB  - Integrin activation involves global conformational changes as demonstrated by
      various functional and structural analyses. The integrin beta hybrid domain is
      proposed to be involved in the propagation of this activation signal. Our
      previous study showed that the integrin beta(2)-specific monoclonal antibody 7E4
      abrogates monoclonal antibody KIM185-activated but not Mg(2+)/EGTA-activated
      leukocyte function-associated antigen-1 (LFA-1; alpha(L)beta(2))-mediated
      adhesion to ICAM-1. Here we investigated the allosteric inhibitory property of
      7E4. By using human/mouse chimeras and substitution mutations, the epitope of 7E4
      was mapped to Val(407), located in the mid-region of the beta(2) hybrid domain.
      Two sets of constitutively active LFA-1 variants were used to examine the effect
      of 7E4 on LFA-1/ICAM-1 binding. 7E4 attenuated the binding of variants that have
      modifications to regions membrane proximal with respect to the beta(2) hybrid
      domain. In contrast, the inhibitory effect was minimal on variants with
      alterations in the alpha(L) I- and beta(2) I-like domains preceding the hybrid
      domain. Furthermore, 7E4 abrogated LFA-1/ICAM-1 adhesion of phorbol 12-myristate
      13-acetate-treated MOLT-4 cells. Our data demonstrate that interaction between
      the hybrid and I-like domain is critical for the regulation of LFA-1-mediated
      adhesion.

PMID- 15456775
TI  - Functional characterization of Escherichia coli DNA adenine methyltransferase, a
      novel target for antibiotics.
AB  - We have characterized Escherichia coli DNA adenine methyltransferase, a critical
      regulator of bacterial virulence. Steady-state kinetics, product inhibition, and
      isotope exchange studies are consistent with a kinetic mechanism in which the
      cofactor S-adenosylmethionine binds first, followed by sequence-specific DNA
      binding and catalysis. The enzyme has a fast methyl transfer step followed by
      slower product release steps, and we directly demonstrate the competence of the
      enzyme cofactor complex. Methylation of adjacent GATC sites is distributive with
      DNA derived from a genetic element that controls the transcription of the
      adjacent genes. This indicates that the first methylation event is followed by
      enzyme release. The affinity of the enzyme for both DNA and S-adenosylmethionine
      was determined. Our studies provide a basis for further structural and functional
      analysis of this important enzyme and for the identification of inhibitors for
      potential therapeutic applications.

PMID- 15456776
TI  - Control of exercise-stimulated muscle glucose uptake by GLUT4 is dependent on
      glucose phosphorylation capacity in the conscious mouse.
AB  - Previous work suggests that normal GLUT4 content is sufficient for increases in
      muscle glucose uptake (MGU) during exercise because GLUT4 overexpression does not
      increase exercise-stimulated MGU. Instead of glucose transport, glucose
      phosphorylation is a primary limitation of exercise-stimulated MGU. It was
      hypothesized that a partial ablation of GLUT4 would not impair exercise
      stimulated MGU when glucose phosphorylation capacity is normal but would do so
      when glucose phosphorylation capacity was increased. Thus, C57BL/6J mice with
      hexokinase II (HKII) overexpression (HK(Tg)), a GLUT4 partial knock-out (G4(+/
      )), or both (HK(Tg) + G4(+/-)) and wild-type (WT) littermates were implanted with
      carotid artery and jugular vein catheters for sampling and infusions at 4 months
      of age. After a 7-day recovery, 5-h fasted mice remained sedentary or ran on a
      treadmill at 0.6 mph for 30 min (n = 9-12 per group) and received a bolus of 2
      deoxy[3H]glucose to provide an index of MGU (Rg). Arterial blood glucose and
      plasma insulin concentrations were similar in WT, G4(+/-), HKTg, and HKTg + G4(+/
      ) mice. Sedentary Rg values were the same in all genotypes in all muscles
      studied, confirming that glucose transport is a significant barrier to basal
      glucose uptake. Gastrocnemius and soleus Rg were greater in exercising compared
      with sedentary mice in all genotypes. During exercise, G4(+/-) mice had a marked
      increase in blood glucose that was corrected by the addition of HK II
      overexpression. Exercise Rg (micromol/100g/min) was not different between WT and
      G4(+/-) mice in the gastrocnemius (24 +/- 5 versus 21 +/- 2) or the soleus (54 +/
      6 versus 70 +/- 7). In contrast, the enhanced exercise Rg observed in HKTg mice
      compared with that in WT mice was absent in HKTg + G4(+/-) mice in both the
      gastrocnemius (39 +/- 7 versus 22 +/- 6) and the soleus (98 +/- 13 versus 65 +/-
      13). Thus, glucose transport is not a significant barrier to exercise-stimulated
      MGU despite a 50% reduction in GLUT4 content when glucose phosphorylation
      capacity is normal. However, when glucose phosphorylation capacity is increased
      by HK II overexpression, GLUT4 availability becomes a marked limitation to
      exercise-stimulated MGU.

PMID- 15456777
TI  - The small GTPase Cdc42 regulates actin polymerization and tension development
      during contractile stimulation of smooth muscle.
AB  - Contractile stimulation induces actin polymerization in smooth muscle tissues and
      cells, and the inhibition of actin polymerization depresses smooth muscle force
      development. In the present study, the role of Cdc42 in the regulation of actin
      polymerization and tension development in smooth muscle was evaluated.
      Acetylcholine stimulation of tracheal smooth muscle tissues increased the
      activation of Cdc42. Plasmids encoding wild type Cdc42 or a dominant negative
      Cdc42 mutant, Asn-17 Cdc42, were introduced into tracheal smooth muscle strips by
      reversible permeabilization, and tissues were incubated for 2 days to allow for
      protein expression. Expression of recombinant proteins was confirmed by
      immunoblot analysis. The expression of the dominant negative Cdc42 mutant
      inhibited contractile force and the increase in actin polymerization in response
      to acetylcholine stimulation but did not inhibit the increase in myosin light
      chain phosphorylation. The expression of wild type Cdc42 had no significant
      effect on force, actin polymerization, or myosin light chain phosphorylation.
      Contractile stimulation increased the association of neuronal Wiskott-Aldrich
      syndrome protein with Cdc42 and the Arp2/3 (actin-related protein) complex in
      smooth muscle tissues expressing wild type Cdc42. The agonist-induced increase in
      these protein interactions was inhibited in tissues expressing the inactive Cdc42
      mutant. We conclude that Cdc42 activation regulates active tension development
      and actin polymerization during contractile stimulation. Cdc42 may regulate the
      activation of neuronal Wiskott-Aldrich syndrome protein and the actin related
      protein complex, which in turn regulate actin filament polymerization initiated
      by the contractile stimulation of smooth muscle.

PMID- 15456778
TI  - Role of a bacterial organic hydroperoxide detoxification system in preventing
      catalase inactivation.
AB  - In the gastric pathogen Helicobacter pylori, catalase (KatA) and alkyl
      hydroperoxide reductase (AhpC) are two highly abundant enzymes that are crucial
      for oxidative stress resistance and survival of the bacterium in the host. Here
      we report a connection unidentified previously between the two stress resistance
      enzymes. We observed that the catalase in ahpC mutant cells in comparison with
      the parent strain is inactivated partially (approximately 50%). The decrease of
      catalase activity is well correlated with the perturbation of the heme
      environment in catalase, as detected by electron paramagnetic resonance
      spectroscopy. To understand the reason for this catalase inactivation, we
      examined the inhibitory effects of hydroperoxides on H. pylori catalase (either
      present in cell extracts or added to the purified enzyme) by monitoring the
      enzyme activity and the EPR signal of catalase. H. pylori catalase is highly
      resistant to its own substrate, without the loss of enzyme activity by treatment
      with a molar ratio of 1:3000 H2O2. However, it inactivated is by lower
      concentrations of organic hydroperoxides (the substrate of AhpC). Treatment with
      a molar ratio of 1:400 t-butyl hydroperoxide resulted in an inactivation of
      catalase by approximately 50%. UV-visible absorption spectra indicated that the
      catalase inactivation by organic hydroperoxides is caused by the formation of a
      catalytically incompetent compound II species. To further support the idea that
      organic hydroperoxides, which accumulate in the ahpC mutant cells, are
      responsible for the inactivation of catalase, we compared the level of lipid
      peroxidation found in ahpC mutant cells with that found in wild type cells. The
      results showed that the total amount of extractable lipid hydroperoxides in the
      ahpC mutant cells is approximately three times that in the wild type cells. Our
      findings reveal a novel role of the organic hydroperoxide detoxification system
      in preventing catalase inactivation.

PMID- 15456779
TI  - Proton-assisted two-electron transfer in natural variants of tetraheme
      cytochromes from Desulfomicrobium Sp.
AB  - The tetraheme cytochrome c3 isolated from Desulfomicrobium baculatum (DSM
      1743)(Dsmb) was cloned, and the sequence analysis showed that this cytochrome
      differs in just three amino acid residues from the cytochrome c3 isolated from
      Desulfomicrobium norvegicum (Dsmn): (DsmnXXDsmb) Thr-37 --> Ser, Val-45 --> Ala,
      and Phe-88 --> Tyr. X-ray crystallography was used to determine the structure of
      cytochrome c3 from Dsmb, showing that it is very similar to the published
      structure of cytochrome c3 from Dsmn. A detailed thermodynamic and kinetic
      characterization of these two tetraheme cytochromes c3 was performed by using NMR
      and visible spectroscopy. The results obtained show that the network of
      cooperativities between the redox and protonic centers is consistent with a
      synergetic process to stimulate the hydrogen uptake activity of hydrogenase. This
      is achieved by increasing the affinity of the cytochrome for protons through
      binding electrons and, reciprocally, by favoring a concerted two-electron
      transfer assisted by the binding of proton(s). The data were analyzed within the
      framework of the differences in the primary and tertiary structures of the two
      proteins, showing that residue 88, close to heme I, is the main cause for the
      differences in the microscopic thermodynamic parameters obtained for these two
      cytochromes c3. This comparison reveals how replacement of a single amino acid
      can tune the functional properties of energy-transducing proteins, so that they
      can be optimized to suit the bioenergetic constraints of specific habitats.

PMID- 15456780
TI  - cDNA cloning and functional expression of a Ca2+-sensing receptor with truncated
      C-terminal tail from the Mozambique tilapia (Oreochromis mossambicus).
AB  - The complete cDNA sequence of the tilapia extracellular Ca(2+)-sensing receptor
      (CaR) was determined. The transcript length of tilapia CaR (tCaR) is 3.4 kbp and
      encodes a 940-amino acid, 7-transmembrane domain protein that is consistent in
      its structural features with known mammalian and piscine CaRs. The tCaR
      extracellular domain includes a characteristic hydrophobic segment, conserved
      cysteine residues that are implicated in receptor dimerization (Cys(129) and
      Cys(131)) and in coupling to the transmembrane domain (nine conserved cysteine
      residues), and conserved serine residues (Ser(147) and Ser(169-171)) that are
      linked to receptor binding of Ca(2+) and L-amino acid-mediated potentiation of
      function. mRNA expression of tCaR was strong in kidney, brain, and gill. Weaker
      expression was observed in pituitary, stomach, intestine, urinary bladder, and
      heart. This distribution is consistent with possible physiological roles in
      endocrine cells, excitable tissues, and ion-transporting barrier epithelia.
      Expression of tCaR mRNA in kidney and intestine was salinity-dependent,
      suggesting a role for the receptor in iono-/osmoregulation in this euryhaline
      teleost species. Human embryonic kidney-293 cells transiently transfected with
      tCaR cDNA demonstrated dose-dependent phospholipase C activation in response to
      elevations in the extracellular Ca(2+) concentration ([Ca(2+)](o)). Functional
      activation of the mitogen-activated protein kinase cascade by high [Ca(2+)](o)
      was also confirmed in these cells despite the naturally occurring truncation of
      the receptor's intracellular tail, which removes segments variably linked in
      mammalian CaRs to filamin-coupled activation of mitogen-activated protein kinase
      cascades. Sensitivity of phospholipase C activation to [Ca(2+)](o) was dependent
      on the ionic strength of the bathing medium, supporting a role in salinity
      sensing.

PMID- 15456781
TI  - Inducible peroxidases mediate nitration of anopheles midgut cells undergoing
      apoptosis in response to Plasmodium invasion.
AB  - Plasmodium berghei invasion of Anopheles stephensi midgut cells causes severe
      damage, induces expression of nitric-oxide synthase, and leads to apoptosis. The
      present study indicates that invasion results in tyrosine nitration, catalyzed as
      a two-step reaction in which nitric-oxide synthase induction is followed by
      increased peroxidase activity. Ookinete invasion induced localized expression of
      peroxidase enzymes, which catalyzed protein nitration in vitro in the presence of
      nitrite and H(2)O(2). Histochemical stainings revealed that when a parasite
      migrates laterally and invades more than one cell, the pattern of induced
      peroxidase activity is similar to that observed for tyrosine nitration. In
      Anopheles gambiae, ookinete invasion elicited similar responses; it induced
      expression of 5 of the 16 peroxidase genes predicted by the genome sequence and
      decreased mRNA levels of one of them. One of these inducible peroxidases has a C
      terminal oxidase domain homologous to the catalytic moiety of phagocyte NADPH
      oxidase and could provide high local levels of superoxide anion (O(2)), that when
      dismutated would generate the local increase in H(2)O(2) required for nitration.
      Chemically induced apoptosis of midgut cells also activated expression of four
      ookinete-induced peroxidase genes, suggesting their involvement in general
      apoptotic responses. The two-step nitration reaction provides a mechanism to
      precisely localize and circumscribe the toxic products generated by defense
      reactions involving nitration. The present study furthers our understanding of
      the biochemistry of midgut defense reactions to parasite invasion and how these
      may influence the efficiency of malaria transmission by anopheline mosquitoes.

PMID- 15456782
TI  - Activation and function of mitochondrial uncoupling protein in plants.
AB  - Plant mitochondrial uncoupling protein (UCP) is activated by superoxide
      suggesting that it may function to minimize mitochondrial reactive oxygen species
      (ROS) formation. However, the precise mechanism of superoxide activation and the
      exact function of UCP in plants are not known. We demonstrate that 4-hydroxy-2
      nonenal (HNE), a product of lipid peroxidation, and a structurally related
      compound, trans-retinal, stimulate a proton conductance in potato mitochondria
      that is inhibitable by GTP (a characteristic of UCP). Proof that the effects of
      HNE and trans-retinal are mediated by UCP is provided by examination of proton
      conductance in transgenic plants overexpressing UCP. These experiments
      demonstrate that the mechanism of activation of UCP is conserved between animals
      and plants and imply a conservation of function. Mitochondria from transgenic
      plants overexpressing UCP were further studied to provide insight into function.
      Experimental conditions were designed to mimic a bioenergetic state that might be
      found in vivo (mitochondria were supplied with pyruvate as well as tricarboxylic
      cycle acids at in vivo cytosolic concentrations and an exogenous ATP sink was
      established). Under such conditions, an increase in UCP protein content resulted
      in a modest but significant decrease in the rate of superoxide production. In
      addition, 13C-labeling experiments revealed an increase in the conversion of
      pyruvate to citrate as a result of increased UCP protein content. These results
      demonstrate that under simulated in vivo conditions, UCP is active and suggest
      that UCP may influence not only mitochondrial ROS production but also
      tricarboxylic acid cycle flux.

PMID- 15456783
TI  - Independent mutations in mouse Vangl2 that cause neural tube defects in looptail
      mice impair interaction with members of the Dishevelled family.
AB  - Mammalian Vangl1 and Vangl2 are highly conserved membrane proteins that have
      evolved from a single ancestral protein Strabismus/Van Gogh found in Drosophila.
      Mutations in the Vangl2 gene cause a neural tube defect (craniorachischisis)
      characteristic of the looptail (Lp) mouse. Studies in model organisms indicate
      that Vangl proteins play a key developmental role in establishing planar cell
      polarity (PCP) and in regulating convergent extension (CE) movements during
      embryogenesis. The role of Vangl1 in these processes is virtually unknown, and
      the molecular function of Vangl1 and Vangl2 in PCP and CE is poorly understood.
      Using a yeast two-hybrid system, glutathione S-transferase pull-down and co
      immunoprecipitation assays, we show that both mouse Vangl1 and Vangl2 physically
      interact with the three members of the cytoplasmic Dishevelled (Dvl) protein
      family. This interaction is shown to require both the predicted cytoplasmic C
      terminal half of Vangl1/2 and a portion of the Dvl protein containing PDZ and DIX
      domains. In addition, we show that the two known Vangl2 loss-of-function
      mutations identified in two independent Lp alleles associated with neural tube
      defects impair binding to Dvl1, Dvl2, and Dvl3. These findings suggest a
      molecular mechanism for the neural tube defect seen in Lp mice. Our observations
      indicate that Vangl1 biochemical properties parallel those of Vangl2 and that
      Vangl1 might, therefore, participate in PCP and CE either in concert with Vangl2
      or independently of Vangl2 in discrete cell types.

PMID- 15456784
TI  - Survivin and p53 modulate quercetin-induced cell growth inhibition and apoptosis
      in human lung carcinoma cells.
AB  - Quercetin, a ubiquitous bioactive plant flavonoid, has been shown to inhibit the
      proliferation of cancer cells. However, the regulation of survivin and p53 on the
      quercetin-induced cell growth inhibition and apoptosis in cancer cells remains
      unclear. In this study, we investigated the roles of survivin and p53 in the
      quercetin-treated human lung carcinoma cells. Quercetin (20-80 mum for 24 h)
      induced the cytotoxicity and apoptosis in both A549 and H1299 lung carcinoma
      cells in a concentration-dependent manner. Additionally, quercetin inhibited the
      cell growth, increased the fractions of G(2)/M phase, and raised the levels of
      cyclin B1 and phospho-cdc2 (threonine 161) proteins. Moreover, quercetin induced
      abnormal chromosome segregation in H1299 cells. The survivin proteins were highly
      expressed in mitotic phase and were located on the midbody of cytokinesis;
      however, the survivin proteins were increased and concentrated on the nuclei
      following quercetin treatment in the lung carcinoma cells. Transfection of a
      survivin antisense oligodeoxynucleotide enhanced the quercetin-induced cell
      growth inhibition and cytotoxicity. Subsequently, quercetin increased the levels
      of total p53 (DO-1), phospho-p53 (serine 15), and p21 proteins, which were
      translocated to the nuclei in A549 cells. Treatment with a specific p53
      inhibitor, pifithrin-alpha, or transfection of a p53 antisense
      oligodeoxynucleotide enhanced the cytotoxicity of the quercetin-treated cells.
      Furthermore, transfection of a small interfering RNA of p21 enhanced the
      quercetin-induced cell death in A549 cells. Together, our results suggest that
      survivin can reduce the cell growth inhibition and apoptosis, and p53 elevates
      the p21 level, which may attenuate the cell death in the quercetin-treated human
      lung carcinoma cells.

PMID- 15456785
TI  - Copper inhibits the water and glycerol permeability of aquaporin-3.
AB  - Aquaporin-3 (AQP3) is an aquaglyceroporin expressed in erythrocytes and several
      other tissues. Erythrocytes are, together with kidney and liver, the main targets
      for copper toxicity. Here we report that both water and glycerol permeability of
      human AQP3 is inhibited by copper. Inhibition is fast, dose-dependent, and
      reversible. If copper is dissolved in carbonic acid-bicarbonate buffer, the
      natural buffer system in our body, doses in the range of those observed in Wilson
      disease and in copper poisoning caused significant inhibition. AQP7, another
      aquaglyceroporin, was insensitive to copper. Three extracellular amino acid
      residues, Trp128, Ser152, and His241, were identified as responsible for the
      effect of copper on AQP3. We have previously shown that Ser152 is involved in
      regulation of AQP3 by pH. The fact that Ser152 mediates regulation of AQP3 by
      copper may explain the phenomenon of exquisite sensitivity of human erythrocytes
      to copper at acidic pH. When AQP3 was co-expressed with another AQP, only
      glycerol but not water permeability was inhibited by copper. Our results provide
      a better understanding of processes that occur in severe copper metabolism
      defects such as Wilson disease and in copper poisoning.

PMID- 15456786
TI  - Functional studies of the Mycobacterium tuberculosis iron-dependent regulator.
AB  - The iron-dependent regulator (IdeR) protein in Mycobacterium tuberculosis, and
      its better characterized homologue, the diphtheria toxin repressor (DtxR) from
      Corynebacterium diphtheriae, are iron-dependent regulatory proteins that control
      gene expression in response to iron availability in bacteria. IdeR regulates
      several genes required for iron uptake and storage including those involved in
      the synthesis of transition metal chelators called siderophores that are linked
      to the M. tuberculosis virulence. In this study, the metal ion and binding
      affinities for IdeR binding to an fxbA operator duplex DNA were estimated using
      fluorescence assays. The Fe(2+), Co(2+), and Ni(2+) affinities of the two metal
      ion binding sites in IdeR that are involved in the activation of the regulator
      DNA binding process in vitro were independently estimated. Binding to the two
      metal ion binding sites is apparently cooperative and the two affinities differ
      significantly. Occupation of the first metal ion binding site causes dimerization
      of IdeR, and the metal ion affinity is about 4 microM for Ni(2+) and much less
      for Fe(2+) and Co(2+). Binding of the second metal ion fully activates IdeR for
      binding to the fxbA operator. The equilibrium metal ion dissociation constants
      for IdeR-fxbA operator binding are approximately 9 microM for Fe(2+), 13 microM
      for Ni(2+), and 23 microM for Co(2+). Interestingly, the natural IdeR cofactor,
      Fe(2+), shows high affinities toward both binding sites. These results provide
      insight into the possible roles for each metal binding site in IdeR activation.

PMID- 15456787
TI  - Physical and functional interaction between Dorfin and Valosin-containing protein
      that are colocalized in ubiquitylated inclusions in neurodegenerative disorders.
AB  - Dorfin, a RING-IBR type ubiquitin ligase (E3), can ubiquitylate mutant superoxide
      dismutase 1, the causative gene of familial amyotrophic lateral sclerosis (ALS).
      Dorfin is located in ubiquitylated inclusions (UBIs) in various neurodegenerative
      disorders, such as ALS and Parkinson's disease (PD). Here we report that Valosin
      containing protein (VCP) directly binds to Dorfin and that VCP ATPase activity
      profoundly contributes to the E3 activity of Dorfin. High through-put analysis
      using mass spectrometry identified VCP as a candidate of Dorfin-associated
      protein. Glycerol gradient centrifugation analysis showed that endogenous Dorfin
      consisted of a 400-600-kDa complex and was co-immunoprecipitated with endogenous
      VCP. In vitro experiments showed that Dorfin interacted directly with VCP through
      its C-terminal region. These two proteins were colocalized in aggresomes in
      HEK293 cells and UBIs in the affected neurons of ALS and PD. VCP(K524A), a
      dominant negative form of VCP, reduced the E3 activity of Dorfin against mutant
      superoxide dismutase 1, whereas it had no effect on the autoubiquitylation of
      Parkin. Our results indicate that VCPs functionally regulate Dorfin through
      direct interaction and that their functional interplay may be related to the
      process of UBI formation in neurodegenerative disorders, such as ALS or PD.

PMID- 15456788
TI  - Evidence that assembly of an active gamma-secretase complex occurs in the early
      compartments of the secretory pathway.
AB  - The gamma-secretase complex, consisting of presenilins (PS), nicastrin (NCT), APH
      1, and PEN-2, catalyzes the intramembranous proteolysis of truncated beta-amyloid
      precursor protein (APP) and Notch derivatives to generate the APP intracellular
      domain (AICD) and Notch intracellular domain (NICD), respectively. To examine the
      intracellular sites in which active gamma-secretase resides, we expressed NCT
      variants harboring either an endoplasmic reticulum (ER) retention signal (NCT-ER)
      or a trans-Golgi network (TGN) targeting motif (NCT-TGN) along with PS1, APH-1,
      and PEN-2 and examined gamma-secretase activity in these settings. In cells
      expressing NCT-ER and the other components, PS1 fragments hyperaccumulated, but
      AICD levels were not elevated. On the other hand, upon coexpression of an ER
      retained APP variant or a constitutionally active Notch mutant, NDeltaE, we
      observed enhanced production of AICD or NICD, respectively, in cells expressing
      NCT-ER. Moreover, we show that membranes from cells expressing NCT-ER, NCT-TGN,
      or NCT-WT contain identical levels of PS1 derivatives that can be photoaffinity
      cross-linked to a biotinylated, benzophenone-derivatized gamma-secretase
      inhibitor. Finally, our cell-free gamma-secretase assays revealed nearly
      equivalent gamma-secretase activities in cells expressing PS1, APH-1, PEN-2, and
      either NCT-WT or NCT-ER. Taken together, we interpret these findings as
      suggesting that active gamma-secretase complex is generated in the early
      compartments of the secretory pathway but that these complexes are transported to
      late compartments in which substrates are encountered and subsequently processed
      within respective transmembrane segments.

PMID- 15456789
TI  - The [URE3] yeast prion results from protein aggregates that differ from amyloid
      filaments formed in vitro.
AB  - The [URE3] yeast prion is a self-propagating inactive form of the Ure2 protein.
      Ure2p is composed of two domains, residues 1-93, the prion-forming domain, and
      the remaining C-terminal part of the protein, which forms the functional domain
      involved in nitrogen catabolite repression. In vitro, Ure2p forms amyloid
      filaments that have been proposed to be the aggregated prion form found in vivo.
      Here we showed that the biochemical characteristics of these two species differ.
      Protease digestions of Ure2p filaments and soluble Ure2p are comparable when
      analyzed by Coomassie staining as by Western blot. However, this finding does not
      explain the pattern specifically observed in [URE3] strains. Antibodies raised
      against the C-terminal part of Ure2p revealed the existence of proteolysis sites
      efficiently cleaved when [URE3], but not wild-type crude extracts, were submitted
      to limited proteolysis. The same antibodies lead to an equivalent digestion
      pattern when recombinant Ure2p (either soluble or amyloid) was analyzed in the
      same way. These results strongly suggest that aggregated Ure2p in [URE3] yeast
      cells is different from the amyloid filaments generated in vitro.

PMID- 15456790
TI  - Use of molecular simulation for mapping conformational CYP2E1 epitopes.
AB  - The identification of the epitopes recognized by autoantibodies against
      cytochrome P450s (CYPs) associated with drug-induced hepatotoxicity is difficult
      because of their conformational nature. In the present investigation, we used a
      novel approach based on the analysis of the whole molecule antigenic capacity
      following single amino acid substitutions to identify the conformational epitopes
      on CYP2E1. A molecular model of CYP2E1 was generated based on the CYP2C5 crystal
      structure, and potential motifs for amino acid exchanges were selected by
      computer simulation in the surface of alpha helices and beta sheets. Fourteen
      modified, apparently correctly folded CYP2E1 variants were produced in
      Escherichia coli and evaluated in immunoprecipitation experiments using sera with
      anti-CYP2E1 autoreactivity from 10 patients with halothane hepatitis and 12
      patients with alcoholic liver disease. Ala substitution of Glu-248 and Lys-251 as
      well as of Lys-324, Lys-342, Lys-420, and Phe-421 severely decreased or abolished
      CYP2E1 recognition by the majority of both the halothane hepatitis and alcoholic
      liver disease sera, whereas the other substitutions had only minor effects. Based
      on the structural model, these substitutions identified two distinct epitopes on
      the CYP2E1 surface corresponding to the G-helix and an area formed by
      juxtaposition of the J' and K'' helices, respectively. The combined use of
      molecular modeling and single amino acid mutagenesis is thus a useful approach
      for the characterization of conformational epitopes recognized by autoantibodies.

PMID- 15456791
TI  - PAN1/NALP2/PYPAF2, an inducible inflammatory mediator that regulates NF-kappaB
      and caspase-1 activation in macrophages.
AB  - Genes encoding proteins with PYRIN/PAAD/DAPIN domains, a nucleotide binding fold
      (NACHT), and leucine rich repeats have recently been recognized as important
      mediators in autoimmune inflammatory disorders. Here we characterize the
      expression and function of a member of the PYRIN and NACHT domain (PAN) family,
      PAN1 (also known as NALP2 and PYPAF2). PAN1 protein expression is regulated by
      lipopolysaccharide (LPS) and interferons (IFNbeta and IFNgamma) in THP-1
      macrophage cells. In gene transfection studies PAN1 manifests an inhibitory
      influence on NF-kappaB activation induced by various pro-inflammatory stimuli,
      including tumor necrosis factor TNFalpha and interleukin-1beta (IL-1beta). Gene
      transfer-mediated elevations in PAN1 protein also suppressed activation of
      IkappaB kinases induced by inflammatory cytokines. Conversely, reducing
      endogenous levels of PAN1 using small interfering RNA enhanced LPS-induced
      production of ICAM-1 (intercellular adhesion molecule 1), an NF-kappaB-dependent
      gene. We also show here that PAN1 binds via its PYRIN domain to ASC, an adapter
      protein involved in caspase-1 activation. This binding is disrupted by mutation
      of the alpha1 helix of ASC. In gene transfer experiments PAN1 enhances caspase-1
      activation and IL-1beta secretion in collaboration with ASC. Conversely, reducing
      endogenous levels of PAN1 using small interfering RNA significantly reduced LPS
      induced secretion of IL-1beta in monocytes. We propose that PAN1 functions as a
      modulator of the activation of NF-kappaB and pro-caspase-1 in macrophages.

PMID- 15456792
TI  - Characterization of a new member of the flavoprotein disulfide reductase family
      of enzymes from Mycobacterium tuberculosis.
AB  - The lpdA (Rv3303c) gene from Mycobacterium tuberculosis encoding a new member of
      the flavoprotein disulfide reductases was expressed in Escherichia coli, and the
      recombinant LpdA protein was purified to homogeneity. LpdA is a homotetramer and
      co-purifies with one molecule of tightly but noncovalently bound FAD and NADP+
      per monomer. Although annotated as a probable lipoamide dehydrogenase in M.
      tuberculosis, LpdA cannot catalyze reduction of lipoyl substrates, because it
      lacks one of two cysteine residues involved in dithiol-disulfide interchange with
      lipoyl substrates and a His-Glu pair involved in general acid catalysis. The
      crystal structure of LpdA was solved by multiple isomorphous replacement with
      anomalous scattering, which confirmed the absence of these catalytic residues
      from the active site. Although LpdA cannot catalyze reduction of disulfide-bonded
      substrates, it catalyzes the NAD(P)H-dependent reduction of alternative electron
      acceptors such as 2,6-dimethyl-1,4-benzoquinone and 5-hydroxy-1,4-naphthaquinone.
      Significant primary deuterium kinetic isotope effects were observed with [4S
      2H]NADH establishing that the enzyme promotes transfer of the C4-proS hydride of
      NADH. The absence of an isotope effect with [4S-2H]NADPH, the low Km value of 0.5
      microm for NADPH, and the potent inhibition of the NADH-dependent reduction of
      2,6-dimethyl-1,4-benzoquinone by NADP+ (Ki approximately 6 nm) and 2'-phospho-ADP
      ribose (Ki approximately 800 nm), demonstrate the high affinity of LpdA for 2'
      phosphorylated nucleotides and that the physiological substrate/product pair is
      NADPH/NADP+ rather than NADH/NAD+. Modeling of NADP+ in the active site revealed
      that LpdA achieves the high specificity for NADP+ through interactions involving
      the 2'-phosphate of NADP+ and amino acid residues that are different from those
      in glutathione reductase.

PMID- 15456793
TI  - Subunit-specific coupling between gamma-aminobutyric acid type A and P2X2
      receptor channels.
AB  - ATP and gamma-aminobutyric acid (GABA) are two fast neurotransmitters co-released
      at central synapses, where they co-activate excitatory P2X and inhibitory GABAA
      (GABA type A) receptors. We report here that co-activation of P2X2 and various
      GABAA receptors, co-expressed in Xenopus oocytes, leads to a functional cross
      inhibition dependent on GABAA subunit composition. Sequential applications of
      GABA and ATP revealed that alphabeta- or alphabetagamma-containing GABAA
      receptors inhibited P2X2 channels, whereas P2X2 channels failed to inhibit gamma
      containing GABAA receptors. This functional cross-talk is independent of membrane
      potential, changes in current direction, and calcium. Non-additive responses
      observed between cation-selective GABAA and P2X2 receptors further indicate the
      chloride independence of this process. Overexpression of minigenes encoding
      either the C-terminal fragment of P2X2 or the intracellular loop of the beta3
      subunit disrupted the functional cross-inhibition. We previously demonstrated
      functional and physical cross-talk between rho1 and P2X2 receptors, which induced
      a retargeting of rho1 channels to surface clusters when co-expressed in
      hippocampal neurons (Boue-Grabot, E., Emerit, M. B., Toulme, E., Seguela, P., and
      Garret, M. (2004) J. Biol. Chem. 279, 6967-6975). Co-expression of P2X2 and
      chimeric rho1 receptors with the C-terminal sequences of alpha2, beta3, or gamma2
      subunits indicated that only rho1-beta3 and P2X2 channels exhibit both functional
      cross-inhibition in Xenopus oocytes and co-clustering/retargeting in hippocampal
      neurons. Therefore, the C-terminal domain of P2X2 and the intracellular loop of
      beta GABAA subunits are required for the functional interaction between ATP- and
      GABA-gated channels. This gamma subunit-dependent cross-talk may contribute to
      the regulation of synaptic activity.

PMID- 15456794
TI  - Critical role of calbindin-D28k in calcium homeostasis revealed by mice lacking
      both vitamin D receptor and calbindin-D28k.
AB  - Calbindin (CaBP)-D28k and CaBP-D9k are cytosolic vitamin D-dependent calcium
      binding proteins long thought to play an important role in transepithelial
      calcium transport. However, recent genetic studies suggest that CaBP-D28k is not
      essential for calcium metabolism. Genetic ablation of this gene in mice leads to
      no calcemic abnormalities. Genetic inactivation of the vitamin D receptor (VDR)
      gene leads to hypocalcemia, secondary hyperparathyroidism, rickets, and
      osteomalacia, accompanied by 90% reduction in renal CaBP-D9k expression but
      little change in CaBP-D28k. To address whether the role of CaBP-D28k in calcium
      homeostasis is compensated by CaBP-D9k, we generated VDR/CaBP-D28k double
      knockout (KO) mice, which expressed no CaBP-D28k and only 10% of CaBP-D9k in the
      kidney. On a regular diet, the double KO mice were more growth-retarded and 42%
      smaller in body weight than VDRKO mice and died prematurely at 2.5-3 months of
      age. Compared with VDRKO mice, the double KO mice had higher urinary calcium
      excretion and developed more severe secondary hyperparathyroidism and rachitic
      skeletal phenotype, which were manifested by larger parathyroid glands, higher
      serum parathyroid hormone levels, much lower bone mineral density, and more
      distorted growth plate with more osteoid formation in the trabecular region. On
      high calcium, high lactose diet, blood-ionized calcium levels were normalized in
      both VDRKO and the double KO mice; however, in contrast to VDRKO mice, the
      skeletal abnormalities were not completely corrected in the double KO mice. These
      results directly demonstrate that CaBP-D28k plays a critical role in maintaining
      calcium homeostasis and skeletal mineralization and suggest that its calcemic
      role can be mostly compensated by CaBP-D9k.

PMID- 15456795
TI  - Spinal neurons that express NK-1 receptors modulate descending controls that
      project through the dorsolateral funiculus.
AB  - Selective ablation of spinal neurons possessing substance P receptors (NK-1
      receptors) using the selective cytotoxin conjugate substance P-saporin (SP-SAP)
      decreases hyperalgesia and central sensitization. The mechanisms by which NK-1
      expressing neurons modulate the excitability of other dorsal horn neurons are
      unclear. Because the majority of NK-1 expressing spinal neurons project
      rostrally, it is possible that they are part of a spinal-supraspinal circuitry
      that contributes to descending modulation of excitability of spinal nociceptive
      neurons. We therefore determined whether ablation of spinal neurons that possess
      the NK-1 receptor altered descending systems that travel via the dorsolateral
      funiculus (DLF). Spontaneous activity and responses of dorsal horn neurons evoked
      by mechanical (von Frey monofilaments) and heat (35-51 degrees C) stimuli were
      determined before and after transection of the DLF and were compared in rats
      pretreated with intrathecal application of vehicle or SP-SAP. In vehicle-treated
      rats, transection of the DLF caused a 233% increase in mean spontaneous activity
      of neurons and enhanced their responses to mechanical and heat stimuli, whereas
      these increases in excitation were blocked in rats pretreated with SP-SAP.
      Importantly, SP-SAP alone had no effect on spontaneous or evoked activity in the
      absence of DLF transection. These results demonstrate that spinal neurons
      expressing the NK-1 receptor appear to play a pivotal role in regulating
      descending systems that modulate activity of nociceptive dorsal horn neurons.

PMID- 15456796
TI  - Fast adaptation of the internal model of gravity for manual interceptions:
      evidence for event-dependent learning.
AB  - We studied how subjects learn to deal with two conflicting sensory environments
      as a function of the probability of each environment and the temporal distance
      between repeated events. Subjects were asked to intercept a visual target moving
      downward on a screen with randomized laws of motion. We compared five protocols
      that differed in the probability of constant speed (0g) targets and accelerated
      (1g) targets. Probability ranged from 9 to 100%, and the time interval between
      consecutive repetitions of the same target ranged from about 1 to 20 min. We
      found that subjects systematically timed their responses consistent with the
      assumption of gravity effects, for both 1 and 0g trials. With training, subjects
      rapidly adapted to 0g targets by shifting the time of motor activation.
      Surprisingly, the adaptation rate was independent of both the probability of 0g
      targets and their temporal distance. Very few 0g trials sporadically interspersed
      as catch trials during immersive practice with 1g trials were sufficient for
      learning and consolidation in long-term memory, as verified by retesting after 24
      h. We argue that the memory store for adapted states of the internal gravity
      model is triggered by individual events and can be sustained for prolonged
      periods of time separating sporadic repetitions. This form of event-related
      learning could depend on multiple-stage memory, with exponential rise and decay
      in the initial stages followed by a sample-and-hold module.

PMID- 15456797
TI  - Staggered development of GABAergic and glycinergic transmission in the MNTB.
AB  - Maturation of some brain stem and spinal inhibitory systems is characterized by a
      shift from GABAergic to glycinergic transmission. Little is known about how this
      transition is expressed in terms of individual axonal inputs and synaptic sites.
      We have explored this issue in the rat medial nucleus of the trapezoid body
      (MNTB). Synaptic responses at postnatal days 5-7 (P5-P7) were small, slow, and
      primarily mediated by GABA(A) receptors. By P8-P12, an additional, faster
      glycinergic component emerged. At these ages, GABA(A), glycine, or both types of
      receptors mediated transmission, even at single synaptic sites. Thereafter,
      glycinergic development greatly accelerated. By P25, evoked inhibitory
      postsynaptic currents (IPSCs) were 10 times briefer and 100 times larger than
      those measured in the youngest group, suggesting a proliferation of synaptic
      inputs activating fast-kinetic receptors. Glycinergic miniature IPSCs (mIPSCs)
      increased markedly in size and decay rate with age. GABAergic mIPSCs also
      accelerated, but declined slightly in amplitude. Overall, the efficacy of
      GABAergic inputs showed little maturation between P5 and P20. Although gramicidin
      perforated-patch recordings revealed that GABA or glycine depolarized P5-P7 cells
      but hyperpolarized P14-P15 cells, the young depolarizing inputs were not
      suprathreshold. In addition, vesicle-release properties of inhibitory axons also
      matured: GABAergic responses in immature rats were highly asynchronous, while in
      older rats, precise, phasic glycinergic IPSCs could transmit even with 500-Hz
      stimuli. Thus development of inhibition is characterized by coordinated
      modifications to transmitter systems, vesicle release kinetics, Cl- gradients,
      receptor properties, and numbers of synaptic inputs. The apparent switch in
      GABA/glycine transmission was predominantly due to enhanced glycinergic function.

PMID- 15456798
TI  - Analysis and design of behavioral experiments to characterize population
      learning.
AB  - In population learning studies, between-subject response differences are an
      important source of variance that must be characterized to identify accurately
      the features of the learning process common to the population. Although learning
      is a dynamic process, current population analyses do not use dynamic estimation
      methods, do not compute both population and individual learning curves, and use
      learning criteria that are less than optimal. We develop a state-space random
      effects (SSRE) model to estimate population and individual learning curves, ideal
      observer curves, and learning trials, and to make dynamic assessments of learning
      between two populations and within the same population that avoid multiple
      hypothesis tests. In an 80-trial study of an NMDA antagonist's effect on the
      ability of rats to execute a set-shift task, our dynamic assessments of learning
      demonstrated that both the treatment and control groups learned, yet, by trial
      35, the treatment group learning was significantly impaired relative to control.
      We used our SSRE model in a theoretical study to evaluate the design efficiency
      of learning experiments in terms of the number of animals per group and number of
      trials per animal required to characterize learning differences between two
      populations. Our results demonstrated that a maximum difference in the
      probability of a correct response between the treatment and control group
      learning curves of 0.07 (0.20) would require 15 to 20 (5 to 7) animals per group
      in an 80 (60)-trial experiment. The SSRE model offers a practical approach to
      dynamic analysis of population learning and a theoretical framework for optimal
      design of learning experiments.

PMID- 15456799
TI  - Prehension synergies in three dimensions.
AB  - The goal of this study was to investigate the conjoint changes of digit
      forces/moments in 3 dimensions during static prehension under external torques
      acting on the object in one plane. The experimental paradigm was similar to
      holding a book vertically in the air where the center of mass of the book is
      located farther from the hand than the points of digit contacts. Three force and
      3 moment components from each digit were recorded during static prehension of a
      customized handle. Subjects produced forces and moments in all 3 directions,
      although the external torques were exerted on the handheld object about only the
      Z-axis. The 3-dimensional response to a 2-dimensional task was explained by the
      cause-effect chain effects prompted by the noncollinearity of the normal forces
      of the thumb and the 4 fingers (represented by the "virtual finger"). Because the
      forces are not collinear (not along the same line), they generate moments of
      force about X- and Y-axes that are negated by the finger forces along the Y- and
      X-directions. The magnitudes of forces produced by lateral fingers (index and
      little) with longer moment arms were larger compared with the central fingers
      (middle and ring). At the virtual finger (an imaginary digit whose mechanical
      action is equivalent to the summed action of the 4 fingers) level, the relative
      contribution of different fractions of the resistive moment produced by subjects
      did not depend on the torque magnitude. We conclude that the CNS 1) solves a
      planar prehension task by producing forces and moments in all 3 directions, 2)
      uses mechanical advantage of fingers, and 3) shares the total torque among finger
      forces and moments in a particular way disregarding the torque magnitude.

PMID- 15456800
TI  - Synaptically recruited apical currents are required to initiate axonal and apical
      spikes in hippocampal pyramidal cells: modulation by inhibition.
AB  - Dendritic voltage-dependent currents and inhibition modulate the information flow
      between synaptic and decision areas. Subthreshold and spike currents are
      sequentially recruited by synaptic potentials in the apical shaft of pyramidal
      cells, which may also decide cell output. We studied the global role of proximal
      apical recruited currents on cell output in vitro and in the anesthetized rat
      after local blockade of Na+ currents in the axon initial segment (AIS) or the
      proximal apical shaft and their modulation by inhibition. Microejection of TTX,
      field potentials, and intrasomatic and intradendritic recordings were employed.
      Dendritic population spikes (PSs) were much smaller in vitro, but the gross
      relations between synaptic and active currents are similar to in vivo. Activation
      of Schaffer collaterals triggered PSs and action potentials (APs) in the apical
      shaft that fully propagated to the axon. However, the specific blockade of
      proximal Na+ currents avoided cell firing, although antidromic PSs and APs
      readily invaded somata. The somatic depolarization of subthreshold excitatory
      postsynaptic potentials (EPSPs) also decreased to about 50%. These results were
      not due to decreased excitatory input by TTX. However, when GABA(A) inhibition
      was locally removed, Schaffer synaptic currents skipped the proximal dendrite and
      fired somatic PSs, although initiated at the AIS. It is concluded that apical
      currents recruited en passant by Schaffer synaptic potentials in the apical shaft
      constitute a necessary amplifier for this input to cause output decision. Local
      inhibition decides when and where an AP will initiate, constituting an efficient
      mechanism to discriminate and weight different inputs.

PMID- 15456801
TI  - Dopamine D1-receptors modulate lateral inhibition between principal cells of the
      nucleus accumbens.
AB  - One of the current hypotheses on dopamine in the physiology of motivation posits
      that this neurotransmitter regulates filtering and selection of inputs to the
      nucleus accumbens. The effects of dopamine (100 microM) and the D1-receptor
      agonist SKF 38393 (20-50 microM) on GABAergic synaptic transmission between pairs
      of principal cells of rat nucleus accumbens were studied by using simultaneous
      dual patch-clamp recordings in acutely prepared brain slices. Both compounds
      attenuated postsynaptic responses induced by presynaptic firing and this effect
      was reversed by the D1-receptor antagonist SCH 23390 (25 microM). This
      attenuating effect of dopamine D1-receptors may act to diminish competitive
      interactions between single projection neurons or ensembles in the nucleus
      accumbens.

PMID- 15456802
TI  - 5-HT prolongs ventral root bursting via presynaptic inhibition of synaptic
      activity during fictive locomotion in lamprey.
AB  - Locomotor pattern generation is maintained by integration of the intrinsic
      properties of spinal central pattern generator (CPG) neurons in conjunction with
      synaptic activity of the neural network. In the lamprey, the spinal locomotor CPG
      is modulated by 5-HT. On a cellular level, 5-HT presynaptically inhibits synaptic
      transmission and postsynaptically inhibits a Ca2+-activated K+ current
      responsible for the slow afterhyperpolarization (sAHP) that follows action
      potentials in ventral horn neurons. To understand the contribution of these
      cellular mechanisms to the modulation of the spinal CPG, we have tested the
      effect of selective 5-HT analogues against fictive locomotion initiated by bath
      application of N-methyl-d-aspartate (NMDA). We found that the 5-HT1D agonist,
      L694-247, dramatically prolongs the frequency of ventral root bursting.
      Furthermore, we show that L694-247 presynaptically inhibits synaptic transmission
      without altering postsynaptic Ca2+-activated K+ currents. We also confirm that 5
      HT inhibits synaptic transmission at concentrations that modulate locomotion. To
      examine the mechanism by which selective presynaptic inhibition modulates the
      frequency of fictive locomotion, we performed voltage- and current-clamp
      recordings of CPG neurons during locomotion. Our results show that 5-HT decreases
      glutamatergic synaptic drive within the locomotor CPG during fictive locomotion.
      Thus we conclude that presynaptic inhibition of neurotransmitter release
      contributes to 5-HT-mediated modulation of locomotor activity.

PMID- 15456803
TI  - Blocking the anoxic depolarization protects without functional compromise
      following simulated stroke in cortical brain slices.
AB  - Within 2 min of stroke onset, neurons and glia in brain regions most deprived of
      blood (the ischemic core) undergo a sudden and profound loss of membrane
      potential caused by failure of the Na+/K+ ATPase pump. This anoxic depolarization
      (AD) represents a collapse in membrane ion selectivity that causes acute neuronal
      injury because neurons simply cannot survive the energy demands of repolarization
      while deprived of oxygen and glucose. In vivo and in live brain slices, the AD
      resists blockade by antagonists of neurotransmitter receptors (including
      glutamate) or by ion channel blockers. Our neuroprotective strategy is to
      identify AD blockers that minimally affect neuronal function. If the conductance
      underlying AD is not normally active, its selective blockade should not alter
      neuronal excitability. Imaging changes in light transmittance in live neocortical
      and hippocampal slices reveal AD onset, propagation, and subsequent dendritic
      damage. Here we identify several sigma-1 receptor ligands that block the AD in
      slices that are pretreated with 10-30 microM of ligand. Blockade prevents
      subsequent cell swelling, dendritic damage, and loss of evoked field potentials
      recorded in layers II/III of neocortex and in the CA1 region of hippocampus. Even
      when AD onset is merely delayed, electrophysiological recovery is markedly
      improved. With ligand treatment, evoked axonal conduction and synaptic
      transmission remain intact. The large nonselective conductance that drives AD is
      still unidentified but represents a prime upstream target for suppressing acute
      neuronal damage arising during the first critical minutes of stroke. Sigma
      receptor ligands provide insight to better define the properties of the channel
      responsible for anoxic depolarization. Video clips of anoxic depolarization and
      spreading depression can be viewed at
      http://anatomy.queensu.ca/faculty/andrew.cfm.

PMID- 15456804
TI  - Response properties of single auditory nerve fibers in the mouse.
AB  - The availability of transgenic and mutant lines makes the mouse a valuable model
      for study of the inner ear, and a powerful window into cochlear function can be
      obtained by recordings from single auditory nerve (AN) fibers. This study
      provides the first systematic description of spontaneous and sound-evoked
      discharge properties of AN fibers in mouse, specifically in CBA/CaJ and C57BL/6
      strains, both commonly used in auditory research. Response properties of 196 AN
      fibers from CBA/CaJ and 58 from C57BL/6 were analyzed, including spontaneous
      rates (SR), tuning curves, rate versus level functions, dynamic range, response
      adaptation, phase-locking, and the relation between SR and these response
      properties. The only significant interstrain difference was the elevation of high
      frequency thresholds in C57BL/6. In general, mouse AN fibers showed similar
      responses to other mammals: sharpness of tuning increased with characteristic
      frequency, which ranged from 2.5 to 70 kHz; SRs ranged from 0 to 120 sp/s, and
      fibers with low SR (<1 sp/s) had higher thresholds, and wider dynamic ranges than
      fibers with high SR. Dynamic ranges for mouse high-SR fibers were smaller (<20
      dB) than those seen in other mammals. Phase-locking was seen for tone frequencies
      <4 kHz. Maximum synchronization indices were lower than those in cat but similar
      to those found in guinea pig.

PMID- 15456805
TI  - Kappa opioids inhibit physiologically identified medullary pain modulating
      neurons and reduce morphine antinociception.
AB  - Microinjection of kappa opioid receptor (KOR) agonists into the rostral
      ventromedial medulla (RVM) attenuates mu-opioid receptor mediated antinociception
      and stress-induced analgesia, yet is also reported to have an analgesic effect.
      To determine how KOR agonists produce both antinociceptive and antianalgesic
      actions within the RVM, the KOR agonist U69593 was microinjected directly into
      the RVM while concurrently monitoring tail flick latencies and RVM neuronal
      activity. Among RVM neurons recorded in vivo, two types show robust changes in
      activity just prior to the nocifensive tail flick reflex: ON cells burst just
      prior to a tail flick and their activity is pronociceptive, whereas OFF cells
      pause just prior to the tail flick and their activity is antinociceptive.
      Although RVM microinjection of U69593 did not affect tail flick latencies on its
      own, it did attenuate the on cell burst, an effect blocked by co-injection of the
      KOR antagonist, nor-binaltorphimine (nor-BNI). Furthermore, U69593 inhibited
      ongoing activity in subsets of OFF cells (4/11) and NEUTRAL cells (3/9).
      Microinjection of U69593 into the RVM also attenuated morphine antinociception
      and suppressed the excitation of off cells. Together with previous in vivo and in
      vitro studies, these results are consistent with the idea that KOR agonists can
      be either pronociceptive through direct inhibition of OFF cells, or antianalgesic
      through both postsynaptic inhibition and presynaptic inhibition of glutamate
      inputs to RVM OFF cells.

PMID- 15456806
TI  - Effects of intratympanic gentamicin on vestibular afferents and hair cells in the
      chinchilla.
AB  - Gentamicin is toxic to vestibular hair cells, but its effects on vestibular
      afferents have not been defined. We treated anesthetized chinchillas with one
      injection of gentamicin (26.7 mg/ml) into the middle ear and made extracellular
      recordings from afferents after 5-25 (early) or 90-115 days (late). The relative
      proportions of regular, intermediate, and irregular afferents did not change
      after treatment. The spontaneous firing rate of regular afferents was lower (P <
      0.001) on the treated side (early: 44.3 +/- 16.3; late: 33.9 +/- 13.2 spikes x s(
      1)) than on the untreated side (54.9 +/- 16.8 spikes x s(-1)). Spontaneous rates
      of irregular and intermediate afferents did not change. The majority of treated
      afferents did not measurably respond to tilt or rotation (82% in the early group,
      76% in the late group). Those that did respond had abnormally low sensitivities
      (P < 0.001). Treated canal units that responded to rotation had mean
      sensitivities only 5-7% of the values for untreated canal afferents. Treated
      otolith afferents had mean sensitivities 23-28% of the values for untreated
      otolith units. Sensitivity to externally applied galvanic currents was unaffected
      for all afferents. Intratympanic gentamicin treatment reduced the histological
      density of all hair cells by 57% (P = 0.04). The density of hair cells with calyx
      endings was reduced by 99% (P = 0.03), although some remaining hair cells had
      other features suggestive of type I morphology. Type II hair cell density was not
      significantly reduced. These findings suggest that a single intratympanic
      gentamicin injection causes partial damage and loss of vestibular hair cells,
      particularly type I hair cells or their calyceal afferent endings, does not
      damage the afferent spike initiation zones, and preserves enough hair cell
      synaptic activity to drive the spontaneous activity of vestibular afferents.

PMID- 15456807
TI  - Role of voluntary drive in encoding an elementary motor memory.
AB  - Motor training consisting of repetitive thumb movements results in encoding of
      motor memories in the primary motor cortex. It is not known if proprioceptive
      input originating in the training movements is sufficient to produce this effect.
      In this study, we compared the ability of training consisting of voluntary
      (active) and passively-elicited (passive) movements to induce this form of
      plasticity. Active training led to successful encoding accompanied by
      characteristic changes in corticomotor excitability, while passive training did
      not. These results support a pivotal role for voluntary motor drive in coding
      motor memories in the primary motor cortex.

PMID- 15456808
TI  - Latencies of climbing fiber inputs to turtle cerebellar cortex.
AB  - Responses of separate regions of rat cerebellar cortex (Cb) to inferior olive
      (IO) stimulation occur with the same latency despite large differences in
      climbing fiber (CF) lengths. Here, the olivocerebellar path of turtle was studied
      because its Cb is an unfoliated sheet on which measurements of latency and CF
      length can be made directly across its entire surface in vitro. During
      extracellular DC recordings at a given Cb position below the molecular layer, IO
      stimulation evoked a large negative field potential with a half-width duration of
      approximately 6.5 ms. On this response were smaller oscillations similar to
      complex spikes. The stimulating electrode was moved to map the IO and the CF path
      from the brain stem to the Cb. The contralateral brain stem region that evoked
      these responses was tightly circumscribed within the medulla, lateral and deep to
      the obex. This response remained when the brain stem was bathed in solutions that
      blocked synaptic transmission. The Cb response to IO stimulation had a peak
      latency of approximately 10 ms that was not dependent on the position of the
      recording electrode across the entire 8-mm rostrocaudal length of the Cb.
      However, for a constant Cb recording position, moving the stimulation across the
      midline to the ipsilateral brain stem and along the lateral wall of the fourth
      ventricle toward the peduncle did shorten the response latency. Therefore a
      synchronous Cb response to CF stimulation seems to be caused by changes in its
      conduction velocity within the entire cerebellar cortex but not within the brain
      stem.

PMID- 15456809
TI  - Calcium/calmodulin-dependent protein kinase II: an unforgettable kinase.

PMID- 15456810
TI  - Regulation of calcium/calmodulin-dependent protein kinase II activation by
      intramolecular and intermolecular interactions.

PMID- 15456811
TI  - Activity-dependent regulation of calcium/calmodulin-dependent protein kinase II
      localization.

PMID- 15456812
TI  - Protein phosphatases and calcium/calmodulin-dependent protein kinase II-dependent
      synaptic plasticity.

PMID- 15456813
TI  - Mouse genetic approaches to investigating calcium/calmodulin-dependent protein
      kinase II function in plasticity and cognition.

PMID- 15456814
TI  - Facilitation of L-type Ca2+ channels in dendritic spines by activation of beta2
      adrenergic receptors.
AB  - We studied the contribution of L-type Ca2+ channels to action potential-evoked
      Ca2+ influx in dendritic spines of CA1 pyramidal neurons and the modulation of
      these channels by the beta2 adrenergic receptor. Backpropagating action
      potentials (bAPs) (three at 50 Hz) were evoked by brief somatic current
      injections, and Ca2+ transients were recorded in proximal basal dendrites and
      associated spines. The R- and T-type Ca2+ channel blocker NiCl2 (100 microm)
      significantly reduced Ca2+ transients in both spines and their parent dendrites
      (approximately 50%), suggesting that these channels are the major source of bAP
      evoked Ca2+ influx in these structures. The L-type Ca2+ channel blockers
      nimodipine and nifedipine (both 10 microm) reduced spine Ca2+ transients by
      approximately 10%, whereas the L-type Ca2+ channel activators FPL 64176 (2,5
      dimethyl-4-[2-(phenylmethyl)benzoyl]-1H-pyrrole-3-carboxylic acid methylester)
      and Bay K 8644 ((+/-)-1,4-dihydro-2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)
      phenyl]-3-pyridine carboxylic acid methyl ester) (both 10 microm) significantly
      enhanced the spine Ca2+ transients by 40-50%. Activation of beta2 adrenergic
      receptors with salbutamol (40 microm) or formoterol (5 microm) resulted in
      significant enhancements of the spine (40-50%) but not dendritic Ca2+ transients.
      This increase was prevented when L-type Ca2+ channels were blocked with
      nimodipine (10 microm) or when cAMP-dependent protein kinase A (PKA) was
      inhibited with KT5720 (3 microm), Rp-cAMPS (Rp-adenosine cyclic 3',5'
      phosphorothioate) (100 microm), or PKI (100 microm). The above data suggest that
      L-type Ca2+ channels are functionally present in dendritic spines of CA1
      pyramidal neurons, contribute to spine Ca2+ influx, and can be modulated by the
      beta2 adrenergic receptor through PKA in a highly compartmentalized manner.

PMID- 15456815
TI  - Repulsion and attraction of axons by semaphorin3D are mediated by different
      neuropilins in vivo.
AB  - Class 3 semaphorins are known to repel and/or sometimes attract axons; however,
      their role in guiding developing axons in the CNS in vivo is still essentially
      unknown. We investigated the role of Semaphorin3D (Sema3D) in the formation of
      the early axon pathways in the zebrafish CNS. Morpholino knock-down shows that
      Sema3D is essential for the correct formation of two early axon pathways. Sema3D
      appears to guide axons of the nucleus of the medial longitudinal fasciculus
      (nucMLF) by repulsion and modulation of fasciculation. In contrast, Sema3D
      appears to be attractive to telencephalic neurons that form the anterior
      commissure (AC). Knock-down of Neuropilin-1A (Npn-1A) phenocopied the effects of
      Sema3D knock-down on the nucMLF axons, and knock-down of either Npn-1A or Npn-2B
      phenocopied the defects of the AC. Furthermore, simultaneous partial knock-down
      experiments demonstrated genetic interactions among Sema3D, Npn-1A, and Npn-2B.
      Together, these data support the hypothesis that Sema3D may act as a repellent
      through receptors containing Npn-1A and as an attractant via receptors containing
      Npn-1A and Npn-2B.

PMID- 15456816
TI  - Brain correlates of language learning: the neuronal dissociation of rule-based
      versus similarity-based learning.
AB  - Language learning is one of the mysteries of human cognition. One of the crucial
      questions is the following: Does acquisition of grammatical knowledge depend
      primarily on abstract rules or on item-specific information? Although there is
      evidence that both mechanisms contribute to language acquisition, their relative
      importance during the process of language learning is unknown. Using an
      artificial grammar paradigm, we show by means of functional magnetic resonance
      imaging that the brain dissociates the two mechanisms: the left anterior
      hippocampus supports similarity-based learning, whereas the left ventral premotor
      cortex is selectively engaged by abstract rule processing. Moreover, data
      analysis over time on learning suggests that similarity-based learning plays a
      nonobligatory role during the initial phase, and that rule-based abstraction
      plays a crucial role during later learning.

PMID- 15456817
TI  - A quantitative map of the circuit of cat primary visual cortex.
AB  - We developed a quantitative description of the circuits formed in cat area 17 by
      estimating the "weight" of the projections between different neuronal types. To
      achieve this, we made three-dimensional reconstructions of 39 single neurons and
      thalamic afferents labeled with horseradish peroxidase during intracellular
      recordings in vivo. These neurons served as representatives of the different
      types and provided the morphometrical data about the laminar distribution of the
      dendritic trees and synaptic boutons and the number of synapses formed by a given
      type of neuron. Extensive searches of the literature provided the estimates of
      numbers of the different neuronal types and their distribution across the
      cortical layers. Applying the simplification that synapses between different cell
      types are made in proportion to the boutons and dendrites that those cell types
      contribute to the neuropil in a given layer, we were able to estimate the
      probable source and number of synapses made between neurons in the six layers.
      The predicted synaptic maps were quantitatively close to the estimates derived
      from the experimental electron microscopic studies for the case of the main
      sources of excitatory and inhibitory input to the spiny stellate cells, which
      form a major target of layer 4 afferents. The map of the whole cortical circuit
      shows that there are very few "strong" but many "weak" excitatory projections,
      each of which may involve only a few percentage of the total complement of
      excitatory synapses of a single neuron.

PMID- 15456818
TI  - Selective enhancement of tonic GABAergic inhibition in murine hippocampal neurons
      by low concentrations of the volatile anesthetic isoflurane.
AB  - Volatile (inhaled) anesthetics cause amnesia at concentrations well below those
      that cause loss of consciousness and immobility; however, the underlying neuronal
      mechanisms are unknown. Although many anesthetics increase inhibitory GABAergic
      synaptic transmission, this effect occurs only at high concentrations (>100
      microm). Molecular targets for low concentrations of inhaled anesthetics have not
      been identified. Here, we report that a tonic inhibitory conductance in
      hippocampal pyramidal neurons generated by alpha5 subunit-containing GABA(A)
      receptors is highly sensitive to low concentrations of the volatile anesthetic
      isoflurane (ISO) (25 and 83.3 microm). The alpha5 subunit is necessary for
      enhancement of the tonic current by these low concentrations of isoflurane
      because potentiation is absent in neurons from alpha5-/- mice. Furthermore, ISO
      (25 microm) potentiated recombinant human alpha5beta3gamma2L GABA(A) receptors,
      whereas this effect was not seen with alpha1beta3gamma2L GABA(A) receptors. These
      studies suggest that an increased tonic inhibition in the hippocampus may
      contribute to amnestic properties of volatile anesthetics.

PMID- 15456819
TI  - Visual response properties in the dorsal lateral geniculate nucleus of mice
      lacking the beta2 subunit of the nicotinic acetylcholine receptor.
AB  - We present a quantitative description of single-cell visual response properties
      in the dorsal lateral geniculate nucleus (dLGN) of anesthetized adult mice
      lacking the beta2 subunit of the nicotinic acetylcholine receptor (beta2-/-) and
      compare these response properties with data from wild-type animals. Some response
      features, including all spatial receptive field characteristics and bursting
      behavior, are entirely normal in beta2-/- dLGN cells. In other respects, the
      responses of beta2-/- dLGN cells are quantitatively abnormal: the mutation is
      associated with higher spontaneous and visually evoked firing rates, faster
      visual response latencies, a preference for higher temporal frequencies, and a
      trend toward greater contrast sensitivity. The normal response properties in the
      beta2-/- dLGN show that none of the many effects of the mutation, including
      disrupted geniculate functional organization and abnormal cholinergic
      transmission, have any effect on spatial response characteristics and bursting
      behavior in dLGN neurons. The abnormal response characteristics in the beta2-/-
      dLGN are most interesting in that they are no worse than normal; any visual
      processing deficits found in studies of the beta2-/- visual cortex must therefore
      arise solely from abnormalities in cortical processing.

PMID- 15456820
TI  - Phase segregation of medial septal GABAergic neurons during hippocampal theta
      activity.
AB  - Septo-hippocampal GABAergic neurons immunoreactive for parvalbumin are thought to
      play a crucial role in the generation of hippocampal theta oscillations
      associated with a specific stage of memory formation. Here we use in vivo
      juxtacellular recording and filling in the medial septum followed by
      immunocytochemical identification of the recorded cells containing parvalbumin to
      determine their firing pattern, phase relationship with hippocampal theta,
      morphology, and to thereby reveal their involvement in the generation of
      hippocampal theta activity. We have demonstrated that GABAergic medial septal
      neurons form two distinct populations exhibiting highly regular bursting activity
      that is tightly coupled to either the trough (178 degrees ) or the peak (330
      degrees ) of hippocampal theta waves. Additionally, different types of bursting
      as well as nonbursting activity patterns were also observed. The morphological
      reconstruction of theta-bursting neurons revealed extensive axon arbors of these
      cells with numerous local collaterals establishing symmetrical synapses; thus,
      synchrony among the septal pacemaker units may be brought about by their
      recurrent collateral interactions. Long projecting axons could also be found
      running dorsally toward the hippocampus and ventrally in the direction of basal
      forebrain regions. We conclude that GABAergic neurons in the medial septum, which
      are known to selectively innervate hippocampal interneurons, are in a position to
      induce rhythmic disinhibition in the hippocampus and other theta-related
      subcortical areas at two different phases of hippocampal theta.

PMID- 15456821
TI  - Role of T-type calcium current in identified D-hair mechanoreceptor neurons
      studied in vitro.
AB  - Different subsets of dorsal root ganglion (DRG) mechanoreceptors transduce low-
      and high-intensity mechanical stimuli. It was shown recently that, in vivo,
      neurotrophin-4 (NT-4)-dependent D-hair mechanoreceptors specifically express a
      voltage-activated T-type calcium channel (Ca(v)3.2) that may be required for
      their mechanoreceptive function. Here we show that D-hair mechanoreceptors can be
      identified in vitro by a rosette-like morphology in the presence of NT-4 and that
      these rosette neurons are almost all absent in DRG cultures taken from NT-4 knock
      out mice. In vitro identification of the D-hair mechanoreceptor allowed us to
      explore the electrophysiological properties of these cells. We demonstrate that
      the T-type Ca(v)3.2 channel induced slow membrane depolarization that contributes
      to lower the voltage threshold for action potential generation and controls spike
      latency after stimulation of D-hair mechanoreceptors. Indeed, the properties of
      the T-type amplifier are particularly well suited to explain the high sensitivity
      of D-hair mechanoreceptors to slowly moving stimuli.

PMID- 15456822
TI  - Identified olfactory ensheathing cells transplanted into the transected dorsal
      funiculus bridge the lesion and form myelin.
AB  - Olfactory ensheathing cells (OECs) prepared from the olfactory bulbs of adult
      transgenic Sprague Dawley (SD) rats expressing green fluorescent protein (GFP)
      were transplanted into a dorsal spinal cord transection lesion of SD rats. Five
      weeks after transplantation, the cells survived within the lesion zone and
      oriented longitudinally along axons that bridged the transection site. Although
      the highest density of GFP cells was within the lesion zone, some cells
      distributed longitudinally outside of the lesion area. Myelinated axons spanning
      the lesion were observed in discrete bundles encapsulated by a cellular element.
      Electron micrographs of spinal cords immunostained with an anti-GFP antibody
      indicated that a majority of the peripheral-like myelinated axons were derived
      from donor OECs. Open-field locomotor behavior was significantly improved in the
      OEC transplantation group. Thus, transplanted OECs derived from the adult
      olfactory bulb can survive and orient longitudinally across a spinal cord
      transection site and form myelin. This pattern of repair is associated with
      improved locomotion.

PMID- 15456823
TI  - Spinal dorsal horn calcium channel alpha2delta-1 subunit upregulation contributes
      to peripheral nerve injury-induced tactile allodynia.
AB  - Peripheral nerve injury induces upregulation of the calcium channel alpha2delta-1
      structural subunit in dorsal root ganglia (DRG) and dorsal spinal cord of spinal
      nerve-ligated rats with neuropathic pain, suggesting a role of the calcium
      channel alpha2delta-1 subunit in central sensitization. To investigate whether
      spinal dorsal horn alpha2delta-1 subunit upregulation derives from increased DRG
      alpha2delta-1 subunit and plays a causal role in neuropathic pain development, we
      examined spinal dorsal hornalpha2delta-1 subunit expression with or without
      dorsal rhizotomy in spinal nerve-ligated rats and its correlation with tactile
      allodynia, a neuropathic pain state defined as reduced thresholds to non-noxious
      tactile stimulation. We also examined the effects of intrathecal alpha2delta-1
      antisense oligonucleotides on alpha2delta-1 subunit expression and neuropathic
      allodynia in the nerve-ligated rats. Our data indicated that spinal nerve injury
      resulted in time-dependentalpha2delta-1 subunit upregulation in the spinal dorsal
      horn that correlated temporally with neuropathic allodynia development and
      maintenance. Dorsal rhizotomy diminished basal level expression and blocked
      injury-induced expression of the spinal dorsal hornalpha2delta-1 subunit and
      reversed injury-induced tactile allodynia. In addition, intrathecal alpha2delta-1
      antisense oligonucleotides blocked injury-induced dorsal horn alpha2delta-1
      subunit upregulation and diminished tactile allodynia. These findings indicate
      that alpha2delta-1 subunit basal expression occurs presynaptically and
      postsynaptically in spinal dorsal horn. Nerve injury induces mainly presynaptic
      alpha2delta-1 subunit expression that derives from increased alpha2delta-1
      subunit in injured DRG neurons. Thus, changes in presynaptic alpha2delta-1
      subunit expression contribute to injury-induced spinal neuroplasticity and
      central sensitization that underlies neuropathic pain development and
      maintenance.

PMID- 15456824
TI  - CXCR3-dependent microglial recruitment is essential for dendrite loss after brain
      lesion.
AB  - Microglia are the resident macrophage population of the CNS and are considered
      its major immunocompetent elements. They are activated by any type of brain
      pathology and can migrate to the lesion site. The chemokine CXCL10 is expressed
      in neurons in response to brain injury and is a signaling candidate for
      activating microglia and directing them to the lesion site. We recently
      identified CXCR3, the corresponding receptor for CXCL10, in microglia and
      demonstrated that this receptor system controls microglial migration. We have now
      tested the impact of CXCR3 signaling on cellular responses after entorhinal
      cortex lesion. In wild-type mice, microglia migrate within the first 3 d after
      lesion into the zone of axonal degeneration, where 8 d after lesion denervated
      dendrites of interneurons are subsequently lost. In contrast, the recruitment of
      microglia was impaired in CXCR3 knock-out mice, and, strikingly, denervated
      distal dendrites were maintained in zones of axonal degeneration. No differences
      between wild-type and knock-out mice were observed after facial nerve axotomy, as
      a lesion model for assessing microglial proliferation. This shows that CXCR3
      signaling is crucial in microglia recruitment but not proliferation, and this
      recruitment is an essential element for neuronal reorganization.

PMID- 15456825
TI  - Abl tyrosine kinase promotes dendrogenesis by inducing actin cytoskeletal
      rearrangements in cooperation with Rho family small GTPases in hippocampal
      neurons.
AB  - Nonreceptor tyrosine kinase Abl is an actin-binding protein and a key regulator
      of neuronal axonal development. Although Abl family kinases also are localized in
      dendrites and are implicated in postsynaptic functions, it is not clear how Abl
      kinases regulate dendritic morphogenesis. Using a developing hippocampal culture
      as a model, we found that the inhibition of Abl kinases by STI571 leads to a
      remarkable simplification of dendritic branching similar to the phenotype caused
      by an increased activity of small GTPase RhoA. Time-lapse microscopic imaging
      reveals a prominent reduction of dendritic branching. In contrast, neurons
      expressing a constitutively active v-abl construct (CA-Abl) show an exuberant
      microtubule-associated protein 2-positive (MAP2-positive) dendrite outgrowth,
      suggesting that Abl modulates dendritic growth. Biochemical assays using a
      glutathione S-transferase pull-down method to determine GTP-bound active Rho
      GTPases demonstrate that Abl inhibition increases RhoA activity but has no effect
      on the activity of Rac1 or Cdc42. At the cellular level the alteration of Abl
      also changes actin organization consistent with RhoA inhibition. Suppression of
      the RhoA downstream effector Rho kinase reverses STI571-induced dendritic
      simplification, demonstrating that activity of the Rho pathway is responsible for
      the Abl-induced changes in dendrogenesis. Furthermore, CA-Abl-induced neurite
      outgrowth is blocked by the expression of a constitutively active RhoA construct.
      The CA-Abl phenotype is not affected by destabilization of microtubules but is
      reversed partially when actin filaments are stabilized with jasplakinolide.
      Together, these studies support a critical role for Abl kinases in regulating
      dendrogenesis by inducing actin cytoskeletal rearrangements in cooperation with
      Rho GTPases.

PMID- 15456826
TI  - Activation of EGL-47, a Galpha(o)-coupled receptor, inhibits function of
      hermaphrodite-specific motor neurons to regulate Caenorhabditis elegans egg
      laying behavior.
AB  - Caenorhabditis elegans egg-laying behavior is inhibited by neurotransmitter
      signaling through the neural G-protein Galpha(o) and serves as a model for
      analyzing Galpha(o) signaling. Mutations that alter egg-laying frequency have
      identified genes encoding a number of signaling proteins that act with Galpha(o),
      but the receptors that activate Galpha(o) remain mostly uncharacterized. To
      further analyze Galpha(o) signaling, we cloned the egl-47 gene, which was
      identified by two dominant mutations that severely inhibit egg laying. egl-47
      encodes two orphan G-protein-coupled receptor isoforms, which share all seven
      transmembrane domains but have different extracellular N termini. Both dominant
      mutations change the same alanine to valine in the sixth transmembrane domain,
      resulting in constitutively activated receptors. Deletion of the egl-47 gene
      caused no detectable egg-laying defects, suggesting that EGL-47 functions
      redundantly, or it inhibits egg laying under specific circumstances as yet
      unidentified. Using promoter::green fluorescent protein transgenes, we found that
      EGL-47 is expressed in a number of neurons, including the hermaphrodite-specific
      neurons (HSNs) that innervate the egg-laying muscles to stimulate contraction.
      Transgenic expression of constitutively active EGL-47 or constitutively active
      Galpha(o) specifically in the HSNs was sufficient to inhibit egg-laying behavior.
      Our results suggest that EGL-47 regulates egg laying by activating Galpha(o) in
      the HSN motor neurons to inhibit their activity. Because several
      neurotransmitters act through Galpha(o) to inhibit HSN function, it appears that
      loss of any one receptor, such as EGL-47, causes only mild defects. Galpha(o)
      apparently integrates signaling from multiple receptors in the HSNs, including
      EGL-47, to set the frequency of egg-laying behavior.

PMID- 15456827
TI  - Akt-1 expression level regulates CNS precursors.
AB  - Although most cells in the embryonic mouse cortex express the serine-threonine
      kinase Akt-1, a small population of progenitors expresses Akt-1 protein at a
      higher level. To determine the functional significance of this difference, we
      used a retrovirus to increase Akt-1 expression in cortical progenitors. Increased
      Akt expression enhanced Akt activation after growth factor stimulation of
      progenitors. In vivo, it promoted retention in progenitor layers, the ventricular
      zone and subventricular zone. In vitro, it enhanced proliferation and survival,
      but did not impair migration. Moreover, it increased the proportion of stem
      cells, defined by a self-renewal assay. These effects did not depend on the Akt
      substrate p21(Cip1). In contrast, rapamycin, an inhibitor of mTOR (mammalian
      target of rapamycin), altered effects of elevated Akt-1 selectively: it
      eliminated the increase in stem cells and reduced the proliferative response, but
      had no effect on survival. The ability of elevated Akt-1 to increase the self
      renewing population therefore depends on a rapamycin-sensitive mechanism
      (presumably inhibition of mTOR activity) but not on p21(Cip1), and can be
      distinguished from its effects on the proliferation and survival of other types
      of progenitors. Our findings suggest that expression of a high level of Akt-1 by
      a subpopulation of cortical progenitors biases their responses to extrinsic
      signals to increase their survival, proliferation, and/or self-renewal.
      Heterogeneity in Akt-1 level among progenitors could therefore allow cells that
      share a microenvironment to respond differently to the same extrinsic signals.

PMID- 15456828
TI  - Dual roles of the C2B domain of synaptotagmin I in synchronizing Ca2+-dependent
      neurotransmitter release.
AB  - Although the vesicular protein synaptotagmin I contains two Ca2+-binding domains
      (C2A and C2B), Ca2+ binding to the C2B domain is more important for triggering
      synchronous neurotransmitter release. We have used point mutagenesis to determine
      the functional contributions of the five negatively charged aspartate (Asp)
      residues that constitute the Ca2+-binding sites in the C2B domain of
      synaptotagmin I. Transfecting wild-type synaptotagmin I DNA into cultured
      hippocampal neurons from synaptotagmin I knock-out mice rescued Ca2+-dependent
      synchronous transmitter release and reduced a slower, asynchronous component of
      release, indicating that synaptotagmin I suppresses asynchronous release.
      Mutating either the second or third Asp residues of the C2B domain potently
      inhibited the ability of synaptotagmin I to rescue synchronous release but did
      not change its ability to suppress asynchronous release. Synaptotagmin I with
      mutations in the first or fourth Asp residues of the C2B domain partially rescued
      synchronous release and partially suppressed asynchronous release, whereas
      neutralizing the fifth Asp residue had no effect on the ability of synaptotagmin
      I to rescue transmitter release. Thus, we conclude that the C2B domain of
      synaptotagmin I regulates neurotransmitter release in at least two ways.
      Synchronous release absolutely requires binding of Ca2+ to the second and third
      Asp residues in this domain. For the suppression of asynchronous release, Ca2+
      binding to the C2B domain of synaptotagmin I apparently is not necessary because
      mutation of the second Asp residue inhibits Ca2+ binding, yet still allows this
      protein to suppress asynchronous release.

PMID- 15456829
TI  - Superlinear population encoding of dynamic hand trajectory in primary motor
      cortex.
AB  - Neural activity in primary motor cortex (MI) is known to correlate with hand
      position and velocity. Previous descriptions of this tuning have (1) been linear
      in position or velocity, (2) depended only instantaneously on these signals,
      and/or (3) not incorporated the effects of interneuronal dependencies on firing
      rate. We show here that many MI cells encode a superlinear function of the full
      time-varying hand trajectory. Approximately 20% of MI cells carry information in
      the hand trajectory beyond just the position, velocity, and acceleration at a
      single time lag. Moreover, approximately one-third of MI cells encode the
      trajectory in a significantly superlinear manner; as one consequence, even small
      position changes can dramatically modulate the gain of the velocity tuning of MI
      cells, in agreement with recent psychophysical evidence. We introduce a compact
      nonlinear "preferred trajectory" model that predicts the complex structure of the
      spatiotemporal tuning functions described in previous work. Finally, observing
      the activity of neighboring cells in the MI network significantly increases the
      predictability of the firing rate of a single MI cell; however, we find
      interneuronal dependencies in MI to be much more locked to external kinematic
      parameters than those described recently in the hippocampus. Nevertheless, this
      neighbor activity is approximately as informative as the hand velocity,
      supporting the view that neural encoding in MI is best understood at a population
      level.

PMID- 15456830
TI  - Patterns of gene expression reveal a temporally orchestrated wound healing
      response in the injured spinal cord.
AB  - Spinal cord injury (SCI) induces a progressive pathophysiology affecting cell
      survival and neurological integrity via complex and evolving molecular cascades
      whose interrelationships are not fully understood. The present experiments were
      designed to: (1) determine potential functional interactions within
      transcriptional expression profiles obtained after a clinically relevant SCI and
      (2) test the consistency of transcript expression after SCI in two genetically
      and immunologically diverse rat strains characterized by differences in T cell
      competence and associated inflammatory responses. By interrogating Affymetrix
      U34A rat genome GeneChip microarrays, we defined the transcriptional expression
      patterns in midcervical contusion lesion sites between 1 and 90 d postinjury of
      athymic nude (AN) and Sprague Dawley (SD) strains. Stringent statistical analyses
      detected significant changes in 3638 probe sets, with 80 genes differing between
      the AN and SD groups. Subsequent detailed functional categorization of these
      transcripts unveiled an overall tissue remodeling response that was common to
      both strains. The functionally organized gene profiles were temporally distinct
      and correlated with repair indices observed microscopically and by magnetic
      resonance microimaging. Our molecular and anatomical observations have identified
      a novel, longitudinal perspective of the post-SCI response, namely, that of a
      highly orchestrated tissue repair and remodeling repertoire with a prominent
      cutaneous wound healing signature that is conserved between two widely differing
      rat strains. These results have significant bearing on the continuing development
      of cellular and pharmacological therapeutics directed at tissue rescue and
      neuronal regeneration in the injured spinal cord.

PMID- 15456831
TI  - ATP-induced non-neuronal cell permeabilization in the rat inner retina.
AB  - The P2X7 subtype holds a special position among P2X receptors because of its
      ability to act both as a classical, ligand-gated ion channel, and as a
      permeabilization pore that can induce cell death under prolonged activation by
      ATP. We have shown previously that, in rat retina, P2X7 receptors are located in
      the inner nuclear layer and ganglion cell layer (GCL). The present study was
      aimed at finding whether retinal P2X7 receptors can act as a mediator of cell
      permeabilization and, if so, at identifying the cellular target(s) of this
      effect. As an indicator of cell permeabilization, we used the fluorescent dye YO
      PRO-1 (molecular weight, 375 Da), which enters cells only through large pores
      like those opened by prolonged or sustained stimulation of P2X(7) receptors and
      binds to DNA, providing a stable labeling of the activated cells. Different
      agonists for P2 receptors were tested for their ability to cause cell
      permeabilization in flat-mounted rat retinas. Among them, only high
      concentrations of ATP (500 microM) and BzATP (2',3'-O-(4-benzoyl-benzoyl)-ATP
      triethylammonium) (100 microM) were able to induce accumulation of YO-PRO-1 in
      the GCL and in the nerve fiber layer, suggesting that different cell types were
      responding to P2X7 stimulation. This effect was blocked by the P2 antagonists
      suramin and PPADS (pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid) and by
      the P2X7-selective inhibitor Brilliant Blue G. To identify the retinal cell types
      affected by ATP-induced permeabilization, we used in vivo labeling techniques.
      Our data clearly reveal that prolonged stimulation of P2X7 receptors elicits
      permeabilization exclusively in microglial cells but not in neurons of the inner
      retina.

PMID- 15456832
TI  - Actin/alpha-actinin-dependent transport of AMPA receptors in dendritic spines:
      role of the PDZ-LIM protein RIL.
AB  - The efficacy of excitatory transmission in the brain depends to a large extent on
      synaptic AMPA receptors, hence the importance of understanding the delivery and
      recycling of the receptors at the synaptic sites. Here we report a novel
      regulation of the AMPA receptor transport by a PDZ (postsynaptic density
      95/Drosophila disc large tumor suppressor zona occludens 1) and LIM (Lin11/rat
      Isl-1/Mec3) domain-containing protein, RIL (reversion-induced LIM protein). We
      show that RIL binds to the AMPA glutamate receptor subunit GluR-A C-terminal
      peptide via its LIM domain and to alpha-actinin via its PDZ domain. RIL is
      enriched in the postsynaptic density fraction isolated from rat forebrain,
      strongly localizes to dendritic spines in cultured neurons, and coprecipitates,
      together with alpha-actinin, in a protein complex isolated by immunoprecipitation
      of AMPA receptors from forebrain synaptosomes. Functionally, in heterologous
      cells, RIL links AMPA receptors to the alpha-actinin/actin cytoskeleton, an
      effect that appears to apply selectively to the endosomal surface-internalized
      population of the receptors. In cultured neurons, an overexpression of
      recombinant RIL increases the accumulation of AMPA receptors in dendritic spines,
      both at the total level, as assessed by immunodetection of endogenous GluR-A
      containing receptors, and at the synaptic surface, as assessed by recording of
      miniature EPSCs. Our results thus indicate that RIL directs the transport of GluR
      A-containing AMPA receptors to and/or within dendritic spines, in an alpha
      actinin/actin-dependent manner, and that such trafficking function promotes the
      synaptic accumulation of the receptors.

PMID- 15456833
TI  - Expression of central glucocorticoid receptors after peripheral nerve injury
      contributes to neuropathic pain behaviors in rats.
AB  - Peripheral glucocorticoid receptors (GRs) play a significant role in the anti
      inflammatory effects of glucocorticoids; however, the role of central GRs in
      nociceptive behaviors after peripheral nerve injury (neuropathic pain behaviors)
      remains unknown. Here we show that the development of neuropathic pain behaviors
      (thermal hyperalgesia and mechanical allodynia) induced by chronic constriction
      nerve injury (CCI) in rats was attenuated by either the GR antagonist RU38486 (4
      = 2 > 1 = 0.5 microg) or a GR antisense oligonucleotide administered
      intrathecally twice daily for postoperative days 1-6. The development of thermal
      hyperalgesia and mechanical allodynia after CCI also was prevented in
      adrenalectomized rats, whereas the GR agonist dexamethasone (100 microg/kg) given
      subcutaneously twice daily for postoperative day 1-6 restored CCI-induced
      neuropathic pain behaviors in the adrenalectomized rats. Mechanistically, CCI
      induced a time-dependent and region-specific expression of neuronal GRs primarily
      within the spinal cord dorsal horn ipsilateral to nerve injury, which showed a
      time course parallel to that of the development of neuropathic pain behaviors.
      Moreover, the expression of neuronal GR after CCI was mediated in part through an
      elevated spinal level of interleukin-6 (IL-6) and protein kinase Cgamma
      (PKCgamma), because intrathecal treatment with an IL-6 antiserum, a PKC inhibitor
      (cheryrithrine), or PKCgamma knock-out substantially reduced the expression of
      neuronal GRs as well as neuropathic pain behaviors after CCI. These findings
      indicate a central role of neuronal GRs in the mechanisms of neuropathic pain
      behaviors in rats and suggest a potential role for GR antagonists in clinical
      management of neuropathic pain.

PMID- 15456834
TI  - ATP excites interneurons and astrocytes to increase synaptic inhibition in
      neuronal networks.
AB  - We investigated the role of extracellular ATP at astrocytes and inhibitory
      GABAergic interneurons in the stratum radiatum area of the mouse hippocampus. We
      show that exogenously applied ATP increased astrocyte intracellular Ca2+ levels
      and depolarized all calbindinand calretinin-positive interneurons in the stratum
      radiatum region of mouse hippocampus, leading to action potential firing and
      enhanced synaptic inhibition onto the postsynaptic targets of interneurons.
      Electrophysiological, pharmacological, and immunostaining studies suggested that
      the effect of ATP on interneurons was mediated by P2Y1 receptors, and that the
      depolarization of interneurons was caused by the concomitant reduction and
      activation of potassium and nonselective cationic conductances, respectively.
      Electrical stimulation of the Schaffer collaterals and perforant path, as well as
      local stimulation within the stratum radiatum, evoked increases in intracellular
      Ca2+ in astrocytes. Facilitation of GABAergic IPSCs onto interneurons also
      occurred during electrical stimulation. Both the stimulation-evoked increases in
      astrocyte Ca2+ levels and facilitation of GABAergic IPSCs were sensitive to
      antagonists of P2Y1 receptors and mimicked by exogenous P2Y1 receptor agonists,
      suggesting that endogenously released ATP can activate P2Y receptors on both
      astrocytes and interneurons. Overall, our data are consistent with the hypothesis
      that ATP released from neurons and astrocytes acts on P2Y1 receptors to excite
      interneurons, resulting in increased synaptic inhibition within intact
      hippocampal circuits.

PMID- 15456835
TI  - Dopamine excites nucleus accumbens neurons through the differential modulation of
      glutamate and GABA release.
AB  - Afferent activity into the nucleus accumbens (NAc) occurs in bursts of action
      potentials. However, it is unclear how synapses in this nucleus respond to such
      bursts, or how these responses are altered by dopamine (DA). I examined the
      effects of DA on excitatory and inhibitory responses to trains of stimuli in rat
      NAc slices. Both EPSCs and IPSCs showed use-dependent depression during trains.
      Although DA inhibited both glutamate and GABA release in the NAc, it
      differentially inhibited release during trains. The inhibition of IPSCs persisted
      throughout the train of stimuli, whereas the inhibition of EPSCs progressively
      diminished. This differential modulation may be explained by a calcium-dependent
      change in the recovery from depression at the GABA synapses, where DA acts by
      decreasing Ca2+ entry. Thus, at later stages of sustained stimulation, DA
      preferentially inhibits GABA release, producing a net excitatory effect during
      bursts suggesting a mechanism for enhancing the contrast between competing inputs
      into the NAc, as well as for affecting long-term plasticity in this structure.

PMID- 15456836
TI  - Altered expression of the delta subunit of the GABAA receptor in a mouse model of
      temporal lobe epilepsy.
AB  - delta Subunit-containing GABA(A) receptors are located predominantly at
      nonsynaptic sites in the dentate gyrus where they may play important roles in
      controlling neuronal excitability through tonic inhibition and responses to GABA
      spillover. Immunohistochemical methods were used to determine whether delta
      subunit expression was altered after pilocarpine-induced status epilepticus in
      C57BL/6 mice in ways that could increase excitability of the dentate gyrus. In
      pilocarpine-treated animals, the normal diffuse labeling of the delta subunit in
      the dentate molecular layer was decreased by 4 d after status epilepticus (latent
      period) and remained low throughout the period of chronic seizures. In contrast,
      diffuse labeling of alpha4 and gamma2 subunits, potentially interrelated GABA(A)
      receptor subunits, was increased during the chronic period. Interestingly, delta
      subunit labeling of many interneurons progressively increased after pilocarpine
      treatment. Consistent with the observed changes in delta subunit labeling,
      physiological studies revealed increased excitability in the dentate gyrus of
      slices obtained from the pilocarpine-treated mice and demonstrated that
      physiological concentrations of the neurosteroid tetrahydrodeoxycorticosterone
      were less effective in reducing excitability in the pilocarpine-treated animals
      than in controls. The findings support the idea that alterations in nonsynaptic
      delta subunit-containing GABA(A) receptors in both principal cells and
      interneurons could contribute to increased seizure susceptibility in the
      hippocampal formation in a temporal lobe epilepsy model.

PMID- 15456837
TI  - Evidence for the involvement of nitric oxide in 3,4-methylenedioxymethamphetamine
      induced serotonin depletion in the rat brain.
AB  - Production of reactive oxygen and/or nitrogen species has been thought to
      contribute to the long-term depletion of brain dopamine and serotonin (5-HT)
      produced by amphetamine derivatives, i.e., methamphetamine and 3,4
      methylenedioxymethamphetamine (MDMA). In the present study, the effects of nitric
      oxide synthase (NOS) inhibitors were examined on the long-term depletion of
      striatal dopamine and/or 5-HT produced by the local perfusion of malonate and
      MDMA or the systemic administration of MDMA. The effect of MDMA on nitric oxide
      formation and nitrotyrosine concentration also was determined. Perfusion with
      MDMA and malonate resulted in a 34% reduction of 5-HT and 49% reduction of
      dopamine concentrations in the striatum. The systemic administration of NOS
      inhibitors, N(omega)-nitro-l-arginine methyl ester hydrochloride and S-methyl-l
      thiocitrulline (S-MTC), and the peroxynitrite decomposition catalyst Fe(III)
      tetrakis (1-methyl-4-pyridyl) porphyrin pentachloride attenuated the MDMA- and
      malonate-induced depletion of striatal dopamine and 5-HT. S-MTC also attenuated
      the depletion of 5-HT in the striatum produced by the systemic administration of
      MDMA without attenuating MDMA-induced hyperthermia. Additionally, the systemic
      administration of MDMA significantly increased the formation of nitric oxide and
      the nitrotyrosine concentration in the striatum. These results support the
      conclusion that MDMA produces reactive nitrogen species in the rat that
      contribute to the neurotoxicity of this amphetamine analog.

PMID- 15456838
TI  - Comparison of the antimuscarinic action of p-fluorohexahydrosiladifenidol in
      ileal and tracheal smooth muscle.
AB  - We investigated the ability of the muscarinic antagonist p
      fluorohexahydrosiladifenidol to inhibit muscarinic agonist-induced contractions
      and phosphoinositide hydrolysis in the guinea pig ileum and trachea. This
      antagonist displayed higher potency at blocking oxotremorine-M-induced
      contractions of the ileum compared with those of the trachea. When estimated
      using a simple model for competitive antagonism, the observed dissociation
      constant of p-fluorohexahydrosiladifenidol exhibited approximately 12-fold higher
      potency in the ileum compared with the trachea. We also investigated the ability
      of p-fluorohexahydrosiladifenidol to affect the inhibition of contraction caused
      by the known competitive muscarinic antagonist atropine. Using resultant analysis
      to analyze this interaction, we found that the true dissociation constant of p
      fluorohexahydrosiladifenidol for competitively antagonizing oxotremorine-M
      induced contractions in the ileum exhibited significantly lower potency than when
      calculated assuming a simple competitive model. In contrast, resultant analysis
      showed little difference between the true and observed potencies of p
      fluorohexahydrosiladifenidol for antagonizing oxotremorine-M-induced contractions
      in the trachea. Using a simple competitive model, we found little difference in
      the observed dissociation constant of p-fluorohexahydrosiladifenidol for
      antagonizing oxotremorine-M-induced phosphoinositide hydrolysis in guinea pig
      ileum and bovine trachea. We also noted that p-fluorohexahydrosiladifenidol (0.3
      1.0 microM) moderately inhibited histamine-induced contractions of ileum but not
      of trachea. Our results suggest that p-fluorohexahydrosiladifenidol does not
      discriminate markedly between M(3) muscarinic receptors in the ileum and trachea
      and that it may posses a more potent, nonmuscarinic inhibitory effect on
      contraction in the ileum.

PMID- 15456839
TI  - Cellular G protein-coupled receptor kinase levels regulate sensitivity of the
      {alpha}2b-adrenergic receptor to undergo agonist-induced down-regulation.
AB  - Chronic coactivation of alpha(2B)- and beta(2)-adrenoceptors (AR) was recently
      reported to down-regulate the alpha(2B)-AR at a lower threshold epinephrine (EPI)
      concentration compared with the activation of alpha(2B)-AR alone. This is the
      result of a modest beta(2)-AR-dependent up-regulation of G protein-coupled
      receptor kinase 3 (GRK3). In the present study, we determined that increasing
      GRK2 or GRK3 levels, independent of beta(2)-AR activation, decreases the EC(50)
      concentration for agonist-induced down-regulation of the alpha(2B)-AR using NG108
      cells with or without overexpression (2- to 10-fold) of GRK2 or GRK3. In parental
      NG108 cells, the EC(50) concentration of EPI required for down-regulation of the
      alpha(2B)-AR is 30 microM. A 2- to 3-fold overexpression of GRK3 in NG108 cells,
      however, reduces the EC(50) to 0.2 microM (a 150-fold decrease), whereas a
      comparable overexpression of GRK2 reduces it to 1 microM (a 30-fold decrease).
      However, when GRK3 or GRK2 in NG108 cells are overexpressed 8- to 10-fold, the
      EC(50) concentration (0.02 microM EPI) for alpha(2B)-AR down-regulation is
      reduced 1000-fold. These data clearly suggest that a modest (2- to 3-fold) up
      regulation of GRK3 is more effective at enhancing the sensitivity of alpha(2B)-AR
      to down-regulation after exposure to EPI than a modest up-regulation of GRK2, but
      that both GRK2 and GRK3 are equally effective at inducing alpha(2B)-AR down
      regulation when up-regulated 8- to 10-fold. To our knowledge, this is the first
      report to systematically demonstrate that GRKs, particularly GRK3, play a pivotal
      role in modulating the agonist EC(50) concentration that down-regulates the
      alpha(2B)-AR and thus adds a new dimension to an already intricate signaling
      network.

PMID- 15456840
TI  - The involvement of the pregnane X receptor in hepatic gene regulation during
      inflammation in mice.
AB  - Inflammation and proinflammatory cytokines suppress the expression of several
      hepatic transporters and metabolic enzymes, often resulting in cholestatic liver
      disease. However, mechanism(s) of this down-regulation have not been fully
      elucidated. As the pregnane X receptor (PXR) is involved in inducing many of
      these hepatic proteins, it is possible that PXR is also involved in their down
      regulation during inflammation. Thus, we compared the effect of inflammation on
      hepatic gene regulation in wild-type (PXR(+/+)) versus PXR-null (PXR(-/-)) mice.
      Treatment of PXR(+/+) but not PXR(-/-) mice with the PXR activators 5-pregnen
      3beta-ol-20-one-16alpha-carbonitrile (PCN) or 17beta-hydroxy-11beta-[4
      dimethylamino phenyl]-17alpha-[1-propynyl] estra-4,9-dien-3-one (RU486) resulted
      in increased mRNA levels of bsep, mdr1a, mrp2, mrp3, oatp2, and cyp3a11,
      indicating involvement of PXR in their regulation. Significantly lower mRNA
      levels of bsep, mdr2, mrp2, mrp3, ntcp, oatp2, and cyp3a11 were found in
      endotoxin-treated PXR(+/+) mice. In endotoxin-treated PXR(-/-) mice, the extent
      of mrp2 suppression was significantly diminished. Changes in MRP2 expression were
      supported by Western blot analysis. Although interleukin (IL)-6 imposed
      significant decreases in the expression of bsep, mrp2, and cyp3a11 in PXR(+/+)
      mice, this was not observed in PXR(-/-) mice. Of note, significantly lower levels
      of PXR mRNA and protein were detected in endotoxin- and IL-6-treated PXR(+/+)
      mice. In addition, endotoxin and IL-6 were also able to suppress PCN-mediated
      induction of bsep, mrp2, cyp3a11, and PXR. Taken together, our results suggest
      that PXR plays a role in the down-regulation of several hepatic proteins during
      inflammation.

PMID- 15456841
TI  - APC at a glance.

PMID- 15456842
TI  - Elaine Fuchs.

PMID- 15456843
TI  - RNA-directed DNA methylation.
AB  - Double-stranded RNAs (dsRNAs) and their 'diced' small RNA products can guide key
      developmental and defense mechanisms in eukaryotes. Some RNA-directed mechanisms
      act at a post-transcriptional level to degrade target messenger RNAs. However,
      dsRNA-derived species can also direct changes in the chromatin structure of DNA
      regions with which they share sequence identity. For example, plants use such RNA
      species to lay down cytosine methylation imprints on identical DNA sequences,
      providing a fundamental mark for the formation of transcriptionally silent
      heterochromatin. Thus, RNA can feed backwards to modulate the accessibility of
      information stored in the DNA of cognate genes. RNA triggers for DNA methylation
      can come from different sources, including invasive viral, transgene or
      transposon sequences, and in some cases are derived from single-stranded RNA
      precursors by RNA-dependent RNA polymerases. The mechanism by which RNA signals
      are translated into DNA methylation imprints is currently unknown, but two plant
      specific types of cytosine methyltransferase have been implicated in this
      process. RNA can also direct heterochromatin formation in fission yeast and
      Drosophila, but in these organisms the process occurs in the absence of DNA
      methylation.

PMID- 15456844
TI  - Cell cycle arrest at the initiation step of human chromosomal DNA replication
      causes DNA damage.
AB  - Cell cycle arrest in response to environmental effects can lead to DNA breaks. We
      investigated whether inhibition of DNA replication during the initiation step can
      lead to DNA damage and characterised a cell-cycle-arrest point at the replication
      initiation step before the establishment of active replication forks. This arrest
      can be elicited by the iron chelators mimosine, ciclopirox olamine or 2,2'
      bipyridyl, and can be reversed by the removal of the drugs or the addition of
      excess iron. Iron depletion induces DNA double-strand breaks in treated cells,
      and activates a DNA damage response that results in focal phosphorylation of
      histone H2AX, focal accumulation of replication protein A (RPA) and ATR (ATM and
      Rad3-related kinase), and activation of CHK1 kinase. Abrogation of the checkpoint
      response does not abolish the cell cycle arrest before the establishment of
      active DNA replication forks. DNA breaks appear concomitantly with the arrival of
      cells at the arrest point and persist upon release from the cell cycle block. We
      conclude that DNA double-strand breaks are the consequence, and not the cause, of
      cell cycle arrest during the initiation step of DNA replication by iron
      chelation.

PMID- 15456845
TI  - A hypophosphorylated form of RPA34 is a specific component of pre-replication
      centers.
AB  - Replication protein A (RPA) is a three subunit single-stranded DNA-binding
      protein required for DNA replication. In Xenopus, RPA assembles in nuclear foci
      that form before DNA synthesis, but their significance in the assembly of
      replication initiation complexes has been questioned. Here we show that the RPA34
      regulatory subunit is dephosphorylated at the exit of mitosis and binds to
      chromatin at detergent-resistant replication foci that co-localize with the
      catalytic RPA70 subunit, at both the initiation and elongation stages of DNA
      replication. By contrast, the RPA34 phosphorylated form present at mitosis is not
      chromatin bound. We further demonstrate that RPA foci assemble on chromatin
      before initiation of DNA replication at sites functionally defined as initiation
      replication sites. Association of RPA with these sites does not require nuclear
      membrane formation, and is sensitive to the S-CDK inhibitor p21. We also provide
      evidence that RPA34 is present at initiation complexes formed in the absence of
      MCM3, but which contain MCM4. In such conditions, replication foci can form, and
      short RNA-primed nascent DNAs of discrete size are synthesized. These data show
      that in Xenopus, the hypophosphorylated form of RPA34 is a component of the pre
      initiation complex.

PMID- 15456846
TI  - Characterisation of Cdc25B localisation and nuclear export during the cell cycle
      and in response to stress.
AB  - Cdc25 phosphatases are essential regulators of the cell cycle. In mammalian
      cells, the Cdc25B isoform activates cyclin A- and cyclin B1-containing complexes
      and is necessary for entry into mitosis. In this report, we characterise the
      subcellular localisation of Cdc25B by immunofluorescence in combination with RNA
      interference to identify specific antibody staining. We find that endogenous
      Cdc25B is mainly nuclear, but a fraction resides in the cytoplasm during the G2
      phase of the cell cycle. Cdc25B starts to appear in S-phase cells and accumulates
      until prophase, after which the protein disappears. We characterise a nuclear
      export sequence in the N-terminus of Cdc25B (amino acids 54-67) that, when
      mutated, greatly reduces the ability of Cdc25B to shuttle in a fluorescence loss
      in photobleaching assay. Mutation of the nuclear export sequence makes Cdc25B
      less efficient in inducing mitosis, suggesting that an important mitotic function
      of Cdc25B occurs in the cytoplasm. Furthermore, we find that when cells are
      exposed to cycloheximide or ultraviolet irradiation, Cdc25B partially
      translocates to the cytoplasm. The dependence of this translocation event on a
      functional nuclear export sequence, an intact serine 323 residue (a 14-3-3
      binding site) and p38 mitogen-activated protein kinase activity indicates that
      the p38 pathway regulates Cdc25B localisation in different situations of cellular
      stress.

PMID- 15456847
TI  - N-glycans, not the GPI anchor, mediate the apical targeting of a naturally
      glycosylated, GPI-anchored protein in polarised epithelial cells.
AB  - The glycosyl-phosphatidylinositol (GPI) anchor mediates the apical sorting of
      proteins in polarised epithelial cells through its interaction with lipid rafts.
      Here we investigated the signals required for the apical targeting of the
      naturally N-glycosylated and GPI-anchored membrane dipeptidase by selective point
      mutation to remove the GPI anchor addition signal or the sites for N-linked
      glycosylation, or both. Activity assays, immunoblotting and immunofluorescence
      microscopy revealed that the constructs lacking the GPI anchor were secreted from
      Madin-Darby canine kidney (MDCK) cells, whereas those retaining the GPI anchor
      were attached at the cell surface, irrespective of the glycosylation status. Wild
      type membrane dipeptidase was expressed preferentially on the apical surface of
      both MDCK and CaCo-2 cells. By contrast, the GPI-anchored construct lacking the N
      glycans was targeted preferentially to the basolateral surface of both cell
      types. In constructs lacking the GPI anchor, the N-glycans also targeted the
      protein to the apical surface. Both the apically targeted, glycosylated and the
      basolaterally targeted, unglycosylated GPI-anchored forms of the protein were
      located in detergent-insoluble lipid rafts. These data indicate that it is the N
      glycans, not the association of the GPI anchor with lipid rafts, which determine
      apical targeting of an endogenously N-glycosylated, GPI-anchored protein in
      polarised epithelial cells.

PMID- 15456848
TI  - Compartmentalization established by claudin-11-based tight junctions in stria
      vascularis is required for hearing through generation of endocochlear potential.
AB  - Claudins are cell adhesion molecules working at tight junctions (TJs) that are
      directly involved in compartmentalization in multicellular organisms. The cochlea
      includes a rather peculiar compartment filled with endolymph. This compartment is
      characterized by high K+ concentration (approximately 150 mM) and a positive
      endocochlear potential (approximately 90 mV; EP), both indispensable conditions
      for cochlear hair cells to transduce acoustic stimuli to electrical signals.
      These conditions are thought to be generated by the stria vascularis, which is
      adjacent to the endolymph compartment. The stria vascularis itself constitutes an
      isolated compartment delineated by two epithelial barriers, marginal and basal
      cell layers. Because TJs of basal cells are primarily composed of claudin-11,
      claudin-11-deficient (Cld11-/-) mice were generated with an expectation that the
      compartmentalization in stria vascularis in these mice would be affected.
      Auditory brainstem response measurements revealed that Cld11-/- mice suffered
      from deafness; although no obvious gross morphological malformations were
      detected in Cld11-/- cochlea, freeze-fracture replica electron microscopy showed
      that TJs disappeared from basal cells of the stria vascularis. In good agreement
      with this, tracer experiments showed that the basal cell barrier was destroyed
      without affecting the marginal cell barrier. Importantly, in the endolymph
      compartment of Cld11-/- cochlea, the K+ concentration was maintained around the
      normal level (approximately 150 mM), whereas the EP was suppressed down to
      approximately 30 mV. These findings indicated that the establishment of the stria
      vascularis compartment, especially the basal cell barrier, is indispensable for
      hearing ability through the generation/maintenance of EP but not of a high K+
      concentration in the endolymph.

PMID- 15456849
TI  - Progesterone inhibits protein kinase A (PKA) in Xenopus oocytes: demonstration of
      endogenous PKA activities using an expressed substrate.
AB  - 3'-5' cyclic adenosine monophosphate (cAMP)-dependent protein kinase, PKA, is
      thought to be a key enzyme that controls prophase arrest in vertebrate oocytes.
      It has long been established that overexpression of the catalytic subunit of PKA
      inhibits hormone-induced frog oocyte maturation whereas overexpression of the
      regulatory subunits induces hormone-independent oocyte maturation. However, the
      activities of endogenous oocyte PKA, or its regulation by the maturation-inducing
      hormone progesterone, have never been directly demonstrated in frog oocytes. We
      have developed a novel expressed substrate for PKA in live oocytes by
      constructing a fusion protein containing an N-terminal myristylation sequence
      (derived from the Src tyrosine kinase) followed by an antigenic epitope tag and a
      substrate motif (the C-terminal cytoplasmic domain of beta2 adrenergic receptor).
      Following mRNA injection, the phosphorylation status of the substrate was
      determined by two-dimensional electrophoresis followed by epitope immunoblotting,
      or alternatively by SDS-PAGE followed by immunoblotting using antibodies
      specifically recognizing the PKA-phosphorylated form of the substrate. In
      prophase oocytes, the expressed protein, myr-HA-beta2AR-C, was fully
      phosphorylated on a single PKA site (Ser346 of human beta2 adrenergic receptor).
      Within one hour of the addition of progesterone, the PKA site became mostly
      dephosphorylated. No re-phosphorylation of the PKA site, and therefore no
      reactivation of PKA, was observed throughout the entire maturation process. To
      demonstrate the generality of this PKA substrate, we analyzed its phosphorylation
      status in COS-7 cells following transfection. We show that dibutyryl cAMP rapidly
      stimulates phosphorylation of the PKA site. These results represent the first
      biochemical demonstration of regulation of endogenous Xenopus oocyte PKA by
      progesterone. Furthermore, myr-HA-beta2AR-C should be widely adaptable as an in
      vivo PKA activity indicator.

PMID- 15456850
TI  - Cathepsin L protease (CPL-1) is essential for yolk processing during
      embryogenesis in Caenorhabditis elegans.
AB  - Cysteine proteases are involved in the degradation of intracellular and
      extracellular proteins, although their precise roles in vivo are not well
      understood. Here we characterise a genetic mutant of the Caenorhabditis elegans
      cathepsin L protease gene cpl-1. CPL-1 is provided maternally and is essential
      for C. elegans embryogenesis. Immunofluorescence and electron microscopy data
      show that yolk endocytosis and initial yolk platelet formation occur normally in
      cpl-1 mutant oocytes and embryos. However, at around the 8-12 cell stage of
      embryogenesis, yolk platelets begin to aggregate and these enlarged yolk
      platelets fill the cytoplasm of cpl-1 mutant embryos. Coincident with this
      aggregation is loss of fluorescence from a yolk green fluorescent protein
      (YP170::GFP). This suggests that loss of CPL-1 activity leads to aberrant
      processing and/or conformational changes in yolk proteins, resulting in abnormal
      platelet fusion. This study has relevance to the abnormal fusion and aggregation
      of lysosomes in cathepsin L-deficient mice and to other lysosomal disorders.

PMID- 15456851
TI  - Phosphorylation by cAMP-dependent protein kinase is essential for synapsin
      induced enhancement of neurotransmitter release in invertebrate neurons.
AB  - Synapsins are synaptic vesicle-associated phosphoproteins involved in the
      regulation of neurotransmitter release and synapse formation; they are substrates
      for multiple protein kinases that phosphorylate them on distinct sites. We have
      previously found that injection of synapsin into Helix snail neurons cultured
      under low-release conditions increases the efficiency of neurotransmitter
      release. In order to investigate the role of phosphorylation in this modulatory
      action of synapsins, we examined the substrate properties of the snail synapsin
      orthologue recently cloned in Aplysia (apSyn) for various protein kinases and
      compared the effects of the intracellular injection of wild-type apSyn with those
      of its phosphorylation site mutants. ApSyn was found to be an excellent in vitro
      substrate for cAMP-dependent protein kinase, which phosphorylated it at high
      stoichiometry on a single site (Ser-9) in the highly conserved domain A, unlike
      the other kinases reported to phosphorylate mammalian synapsins, which
      phosphorylated apSyn to a much lesser extent. The functional effect of apSyn
      phosphorylation by cAMP-dependent protein kinase on neurotransmitter release was
      studied by injecting wild-type or Ser-9 mutated apSyn into the soma of Helix
      serotonergic C1 neurons cultured under low-release conditions, i.e. in contact
      with the non-physiological target neuron C3. In this model of impaired
      neurotransmitter release, the injection of wild-type apSyn induced a significant
      enhancement of release. This enhancement was virtually absent after injection of
      the non-phosphorylatable mutant (Ser-9-->Ala), but it was maintained after
      injection of the pseudophosphorylated mutant (Ser-9-->Asp). These functional
      effects of apSyn injection were paralleled by marked ultrastructural changes in
      the C1 neuron, with the formation of extensive interdigitations of neurite-like
      processes containing an increased complement of C1 dense core vesicles at the
      sites of cell-to-cell contact. This structural rearrangement was virtually absent
      in mock-injected C1 neurons or after injection of the non-phosphorylatable apSyn
      mutant. These data indicate that phosphorylation of synapsin domain A is
      essential for the synapsin-induced enhancement of neurotransmitter release and
      suggest that endogenous kinases phosphorylating this domain play a central role
      in the regulation of the efficiency of the exocytotic machinery.

PMID- 15456852
TI  - Cathepsin D released by lactating rat mammary epithelial cells is involved in
      prolactin cleavage under physiological conditions.
AB  - The 16 kDa prolactin fragment arises from partial proteolysis of the native 23
      kDa prolactin pituitary hormone. The mammary gland has been involved in this
      processing, although it has not been clarified whether it occurs in stroma or
      epithelial cells or extracellularly. Also, the processing enzyme has not been
      defined yet. Here we show that the incubation medium of stroma-deprived mammary
      acini from lactating rat contains an enzymatic activity able to cleave, in a
      temperature- and time-dependent fashion, the 23 kDa prolactin to generate a 16
      kDa prolactin detectable under reducing conditions. This cleavage was not
      impaired in the presence of hirudin, a thrombin inhibitor, but strongly weakened
      in the presence of pepstatin A, a cathepsin D inhibitor. Cathepsin D immuno
      depletion abolished the capability of acini-conditioned medium to cleave the 23
      kDa prolactin. Brefeldin A treatment of acini, a condition that largely abolished
      the apical secretion of milk proteins, did not impair the secretion of the
      enzymatically active single chain of cathepsin D. These results show that mature
      cathepsin D from endosomes or lysosomes is released, likely at the baso-lateral
      site of mammary epithelial cells, and that a cathepsin D-dependent activity is
      required to effect, under physiological conditions, the cleavage of 23 kDa
      prolactin in the extracellular medium. This is the first report demonstrating
      that cathepsin D can perform a limited proteolysis of a substrate at
      physiological pH outside the cell.

PMID- 15456853
TI  - Visualization of SHP-1-target interaction.
AB  - Signaling of receptor tyrosine kinases (RTKs) is regulated by protein-tyrosine
      phosphatases (PTPs). We previously discovered the efficient downregulation of Ros
      RTK signaling by the SH2 domain PTP SHP-1, which involves a direct interaction of
      both molecules. Here, we studied the mechanism of this interaction in detail.
      Phosphopeptides representing the SHP-1 candidate binding sites in the Ros
      cytoplasmic domain, pY2267 and pY2327, display high affinity binding to the SHP-1
      N-terminal SH2 domain (Kd=217 nM and 171 nM, respectively). Y2327 is, however, a
      poor substrate of Ros kinase and, therefore, contributes little to SHP-1 binding
      in vitro. To explore the mechanism of association in intact cells, functional
      fluorescent fusion proteins of Ros and SHP-1 were generated. Complexes of both
      molecules could be detected by Forster resonance energy transfer (FRET) in intact
      HEK293 and COS7 cells. As expected, the association required the functional SHP-1
      N-terminal SH2 domain. Unexpectedly, pY2267 and pY2327 both contributed to the
      association. Mutation of Y2327 reduced constitutive association in COS7 cells.
      Ligand-dependent association was abrogated upon mutation of Y2267 but remained
      intact when Y2327 was mutated. A phosphopeptide representing the binding site
      pY2267 was a poor substrate for SHP-1, whereas Ros activation loop
      phosphotyrosines were effectively dephosphorylated. We propose a model for SHP-1
      Ros interaction in which ligand-stimulated phosphorylation of Ros Y2267 by Ros,
      phosphorylation of Y2327 by a heterologous kinase, and inactivation of Ros by SHP
      1-mediated dephosphorylation play a role in the regulation of complex stability.

PMID- 15456854
TI  - Caenorhabditis elegans syndecan (SDN-1) is required for normal egg laying and
      associates with the nervous system and the vulva.
AB  - In Caenorhabditis elegans, the identification of many enzymes involved in the
      synthesis and modification of glycosaminoglycans (GAGs), essential components of
      proteoglycans, has attained special attention in recent years. Mutations in all
      the genes that encode for GAG biosynthetic enzymes show defects in the
      development of the vulva, specifically in the invagination of the vulval
      epithelium. Mutants for certain heparan sulfate modifying enzymes present axonal
      and cellular guidance defects in specific neuronal classes. Although most of the
      enzymes involved in the biosynthesis and modification of heparan sulfate have
      been characterized in C. elegans, little is known regarding the core proteins to
      which these GAGs covalently bind in proteoglycans. A single syndecan homologue
      (sdn-1) has been identified in the C. elegans genome through sequence analysis.
      In the present study, we show that C. elegans synthesizes sulfated proteoglycans,
      seen as three distinct species in western blot analysis. In the sdn-1 (ok449)
      deletion mutant allele we observed the lack of one species, which corresponds to
      a 50 kDa product after heparitinase treatment. The expression of sdn-1 mRNA and
      sequencing revealed that sdn-1 (ok449) deletion mutants lack two glycosylation
      sites. Hence, the missing protein in the western blot analysis probably
      corresponds to SDN-1. In addition, we show that SDN-1 localizes to the C. elegans
      nerve ring, nerve cords and to the vulva. SDN-1 is found specifically
      phosphorylated in nerve ring neurons and in the vulva, in both wild-type worms
      and sdn-1 (ok449) deletion mutants. These mutants show a defective egg-laying
      phenotype. Our results show for the first time, the identification, localization
      and some functional aspects of syndecan in the nematode C. elegans.

PMID- 15456855
TI  - Sexual dimorphism of rat liver nuclear proteins: regulatory role of growth
      hormone.
AB  - Many genes are expressed in mammalian liver in a sexually dimorphic manner. DNA
      microarray analysis has shown that growth hormone (GH) and its sex-dependent
      pattern of pituitary secretion play a major role in establishing the sexually
      dimorphic patterns of liver gene expression. However, GH may exert effects on
      protein post-translational modification and nuclear localization that are not
      reflected at the mRNA level. To investigate these potential effects of GH, we
      used two-dimensional gel electrophoresis followed by LC-MS/MS to: 1) identify rat
      liver nuclear proteins whose abundance or state of post-translational
      modification displays sex-dependent differences; and 2) determine the role of the
      plasma GH profile in establishing these differences. Nuclear extracts prepared
      from livers of individual male (n=9) and female (n=5) adult rats, and from males
      given GH by continuous infusion for 7 days to feminize liver gene expression (n=5
      rats), were resolved by two-dimensional electrophoresis. Image analysis of SYPRO
      Ruby-stained gels revealed 165 sexually dimorphic protein spots that differ in
      normalized volume between male and female groups by >1.5-fold at p<0.05. Sixty of
      these proteins exhibited female-like changes in spot abundance following
      continuous GH treatment. Comparison of male and GH-treated male groups revealed
      130 proteins that displayed >1.5-fold differences in abundance, with 60 of these
      GH-responsive spots being sexually dimorphic. Thus, GH plays an important role in
      establishing the sex-dependent differences in liver nuclear protein content.
      Twenty-eight of the sexually dimorphic and/or GH-regulated protein spots were
      identified by LC-MS/MS. Proteins identified include regucalcin, nuclear factor
      45, and heterogeneous nuclear ribonucleoproteins A3, D-like, and K, in addition
      to proteins such as GST, normally associated with cytosolic extracts but also
      reported to be localized in the nucleus.

PMID- 15456856
TI  - Gfi/Pag-3/senseless zinc finger proteins: a unifying theme?

PMID- 15456857
TI  - Notch activation induces endothelial cell cycle arrest and participates in
      contact inhibition: role of p21Cip1 repression.
AB  - Although previous studies demonstrate that appropriate Notch signaling is
      required during angiogenesis and in vascular homeostasis, the mechanisms by which
      Notch regulates vascular function remain to be elucidated. Here, we show that
      activation of the Notch pathway by the ligand Jagged1 reduces the proliferation
      of endothelial cells. Notch activation inhibits proliferation of endothelial
      cells in a cell-autonomous manner by inhibiting phosphorylation of the
      retinoblastoma protein (Rb). During cell cycle entry, p21Cip1 is upregulated in
      endothelial cells. Activated Notch inhibits mitogen-induced upregulation of
      p21Cip1 and delays cyclin D-cdk4-mediated Rb phosphorylation. Notch-dependent
      repression of p21Cip1 prevents nuclear localization of cyclin D and cdk4. The
      necessity of p21Cip1 for nuclear translocation of cyclin D-cdk4 and S-phase entry
      in endothelial cells was demonstrated by targeted downregulation of p21Cip1 by
      using RNA interference. We further demonstrate that when endothelial cells reach
      confluence, Notch is activated and p21Cip1 is downregulated. Inhibition of the
      Notch pathway at confluence prevents p21Cip1 downregulation and induces Rb
      phosphorylation. We suggest that Notch activation contributes to contact
      inhibition of endothelial cells, in part through repression of p21Cip1
      expression.

PMID- 15456858
TI  - Genome-wide analysis of the relationship between transcriptional regulation by
      Rpd3p and the histone H3 and H4 amino termini in budding yeast.
AB  - The histone amino termini have emerged as key targets for a variety of modifying
      enzymes that function as transcriptional coactivators and corepressors. However,
      an important question that has remained largely unexplored is the extent to which
      specific histone amino termini are required for the activating and repressive
      functions of these enzymes, Here we address this issue by focusing on the
      prototypical histone deacetylase, Rpd3p, in the budding yeast Saccharomyces
      cerevisiae. We show that targeting Rpd3p to a reporter gene in this yeast can
      partially repress transcription when either the histone H3 or the histone H4
      amino terminus is deleted, indicating that the "tails" are individually
      dispensable for repression by Rpd3p. In contrast, we find that the effect of rpd3
      gene disruption on global gene expression is considerably reduced in either a
      histone H3Delta1-28 (H3 lacking the amino-terminal 28 amino acids) or a histone
      H4(K5,8,12,16Q) (H4 with lysine residues 5, 8, 12, and 16 changed to glutamine
      residues) background compared to the wild-type background, indicating a
      requirement for one or both of these histone tails in Rpd3p-mediated regulation
      for many genes. These results suggest that acetylation of either the H3 or the H4
      amino terminus could suffice to allow the activation of such genes. We also
      examine the relationship between H3 tails and H4 tails in global gene expression
      and find substantial overlap among the gene sets regulated by these histone
      tails. We also show that the effects on genome-wide expression of deleting the H3
      or H4 amino terminus are similar but not identical to the effects of mutating the
      lysine residues in these same regions. These results indicate that the gene
      regulatory potential of the H3 and H4 amino termini is substantially but not
      entirely contained in these modifiable lysine residues.

PMID- 15456859
TI  - Interplay of SOX and POU factors in regulation of the Nestin gene in neural
      primordial cells.
AB  - Intermediate-filament Nestin and group B1 SOX transcription factors (SOX1/2/3)
      are often employed as markers for neural primordium, suggesting their regulatory
      link. We have identified adjacent and essential SOX and POU factor binding sites
      in the Nestin neural enhancer. The 30-bp sequence of the enhancer including these
      sites (Nes30) showed a nervous system-specific and SOX-POU-dependent enhancer
      activity in multimeric forms in transfection assays and was utilized in assessing
      the specificity of the synergism; combinations of either group B1 or group C SOX
      (SOX11) with class III POU proved effective. In embryonic day 13.5 mouse spinal
      cord, Nestin was expressed in the cells with nuclei in the ventricular and
      subventricular zones. SOX1/2/3 expression was confined to the nuclei of the
      ventricular zone; SOX11 localized to the nuclei of both subventricular (high
      level expression) and intermediate (low-level expression) zones. Class III POU
      (Brn2) was expressed at high levels, localizing to the nucleus in the ventricular
      and subventricular zones; moderate expression was observed in the intermediate
      zone, distributed in the cytoplasm. These data support the model that synergic
      interactions between group B1/C SOX and class III POU within the nucleus
      determine Nestin expression. Evidence also suggests that such interactions are
      involved in the regulation of neural primordial cells.

PMID- 15456860
TI  - Bone-specific transcription factor Runx2 interacts with the 1alpha,25
      dihydroxyvitamin D3 receptor to up-regulate rat osteocalcin gene expression in
      osteoblastic cells.
AB  - Bone-specific transcription of the osteocalcin (OC) gene is regulated principally
      by the Runx2 transcription factor and is further stimulated in response to
      1alpha,25-dihydroxyvitamin D3 via its specific receptor (VDR). The rat OC gene
      promoter contains three recognition sites for Runx2 (sites A, B, and C). Mutation
      of sites A and B, which flank the 1alpha,25-dihydroxyvitamin D3-responsive
      element (VDRE), abolishes 1alpha,25-dihydroxyvitamin D3-dependent enhancement of
      OC transcription, indicating a tight functional relationship between the VDR and
      Runx2 factors. In contrast to most of the members of the nuclear receptor family,
      VDR possesses a very short N-terminal A/B domain, which has led to the suggestion
      that its N-terminal region does not contribute to transcriptional enhancement.
      Here, we have combined transient-overexpression, coimmunoprecipitation, in situ
      colocalization, chromatin immunoprecipitation, and glutathione S-transferase pull
      down analyses to demonstrate that in osteoblastic cells expressing OC, VDR
      interacts directly with Runx2 bound to site B, which is located immediately
      adjacent to the VDRE. This interaction contributes significantly to 1alpha,25
      dihydroxyvitamin D3-dependent enhancement of the OC promoter and requires a
      region located C terminal to the runt homology DNA binding domain of Runx2 and
      the N-terminal region of VDR. Together, our results indicate that Runx2 plays a
      key role in the 1alpha,25-dihydroxyvitamin D3-dependent stimulation of the OC
      promoter in osteoblastic cells by further stabilizing the interaction of the VDR
      with the VDRE. These studies demonstrate a novel mechanism for combinatorial
      control of bone tissue-specific gene expression. This mechanism involves the
      intersection of two major pathways: Runx2, a "master" transcriptional regulator
      of osteoblast differentiation, and 1alpha,25-dihydroxyvitamin D3, a hormone that
      promotes expression of genes associated with these terminally differentiated bone
      cells.

PMID- 15456861
TI  - Severe global DNA hypomethylation blocks differentiation and induces histone
      hyperacetylation in embryonic stem cells.
AB  - It has been reported that DNA methyltransferase 1-deficient (Dnmt1-/-) embryonic
      stem (ES) cells are hypomethylated (20% CpG methylation) and die through
      apoptosis when induced to differentiate. Here, we show that Dnmt[3a-/-,3b-/-] ES
      cells with just 0.6% of their CpG dinucleotides behave differently: the majority
      of cells within the culture are partially or completely blocked in their ability
      to initiate differentiation, remaining viable while retaining the stem cell
      characteristics of alkaline phosphatase and Oct4 expression. Restoration of DNA
      methylation levels rescues these defects. Severely hypomethylated Dnmt[3a-/-,3b-/
      ] ES cells have increased histone acetylation levels, and those cells that can
      differentiate aberrantly express extraembryonic markers of differentiation.
      Dnmt[3a-/-,3b-/-] ES cells with >10% CpG methylation are able to terminally
      differentiate, whereas Dnmt1-/- ES cells with 20% of the CpG methylated cannot
      differentiate. This demonstrates that successful terminal differentiation is not
      dependent simply on adequate methylation levels. There is an absolute requirement
      that the methylation be delivered by the maintenance enzyme Dnmt1.

PMID- 15456862
TI  - Neuronal LRP1 functionally associates with postsynaptic proteins and is required
      for normal motor function in mice.
AB  - The LDL receptor-related protein 1 (LRP1) is a multifunctional cell surface
      receptor that is highly expressed on neurons. Neuronal LRP1 in vitro can mediate
      ligand endocytosis, as well as modulate signal transduction processes. However,
      little is known about its role in the intact nervous system. Here, we report that
      mice that lack LRP1 selectively in differentiated neurons develop severe
      behavioral and motor abnormalities, including hyperactivity, tremor, and
      dystonia. Since their central nervous systems appear histoanatomically normal, we
      suggest that this phenotype is likely attributable to abnormal neurotransmission.
      This conclusion is supported by studies of primary cultured neurons that show
      that LRP1 is present in close proximity to the N-methyl-D-aspartate (NMDA)
      receptor in dendritic synapses and can be coprecipitated with NMDA receptor
      subunits and the postsynaptic density protein PSD-95 from neuronal cell lysates.
      Moreover, treatment with NMDA, but not dopamine, reduces the interaction of LRP1
      with PSD-95, indicating that LRP1 participates in transmitter-dependent
      postsynaptic responses. Together, these findings suggest that LRP1, like other
      ApoE receptors, can modulate synaptic transmission in the brain.

PMID- 15456863
TI  - Increased sensitivity to UV radiation in mice with a p53 point mutation at
      Ser389.
AB  - Phosphorylation is important for p53 protein stabilization and activation after
      DNA damage. Serine 389 of p53 is specifically phosphorylated after UV
      irradiation, whereas gamma radiation activates p53 through a different pathway.
      To study the in vivo significance of p53 phosphorylation at serine 389, we
      generated a physiological mouse model in which p53 phosphorylation at serine 389
      is abolished by alanine substitution. Homozygous mutant p53.S389A mice are viable
      and have an apparently normal phenotype. However, cells isolated from these mice
      are partly compromised in transcriptional activation of p53 target genes and
      apoptosis after UV irradiation, whereas gamma radiation-induced responses are not
      affected. Moreover, p53.S389A mice show increased sensitivity to UV-induced skin
      tumor development, signifying the importance of serine 389 phosphorylation for
      the tumor-suppressive function of p53.

PMID- 15456864
TI  - Functional similarity between the peroxisomal PTS2 receptor binding protein
      Pex18p and the N-terminal half of the PTS1 receptor Pex5p.
AB  - Within the extended receptor cycle of peroxisomal matrix import, the function of
      the import receptor Pex5p comprises cargo recognition and transport. While the C
      terminal half (Pex5p-C) is responsible for PTS1 binding, the contribution of the
      N-terminal half of Pex5p (Pex5p-N) to the receptor cycle has been less clear.
      Here we demonstrate, using different techniques, that in Saccharomyces cerevisiae
      Pex5p-N alone facilitates the import of the major matrix protein Fox1p. This
      finding suggests that Pex5p-N is sufficient for receptor docking and cargo
      transport into peroxisomes. Moreover, we found that Pex5p-N can be functionally
      replaced by Pex18p, one of two auxiliary proteins of the PTS2 import pathway. A
      chimeric protein consisting of Pex18p (without its Pex7p binding site) fused to
      Pex5p-C is able to partially restore PTS1 protein import in a PEX5 deletion
      strain. On the basis of these results, we propose that the auxiliary proteins of
      the PTS2 import pathway fulfill roles similar to those of the N-terminal half of
      Pex5p in the PTS1 import pathway.

PMID- 15456865
TI  - Epiregulin is not essential for development of intestinal tumors but is required
      for protection from intestinal damage.
AB  - Epiregulin, an epidermal growth factor family member, acts as a local signal
      mediator and shows dual biological activity, stimulating the proliferation of
      fibroblasts, hepatocytes, smooth muscle cells, and keratinocytes while inhibiting
      the growth of several tumor-derived epithelial cell lines. The epiregulin gene
      (Ereg) is located on mouse chromosome 5 adjacent to three other epidermal growth
      factor family members, epigen, amphiregulin, and betacellulin. Gene targeting was
      used to insert a lacZ reporter into the mouse Ereg locus and to ablate its
      function. Although epiregulin is broadly expressed and regulated both spatially
      and temporally, Ereg null mice show no overt developmental defects, reproductive
      abnormalities, or altered liver regeneration. Additionally, in contrast to
      previous hypotheses, Ereg deficiency does not alter intestinal cancer
      susceptibility, as assayed in the ApcMin model, despite showing robust expression
      in developing tumors. However, Ereg null mice are highly susceptible to cancer
      predisposing intestinal damage caused by oral administration of dextran sulfate
      sodium.

PMID- 15456866
TI  - The cyclin A1-CDK2 complex regulates DNA double-strand break repair.
AB  - Vertebrates express two A-type cyclins; both associate with and activate the CDK2
      protein kinase. Cyclin A1 is required in the male germ line, but its molecular
      functions are incompletely understood. We observed specific induction of cyclin
      A1 expression and promoter activity after UV and gamma-irradiation which was
      mediated by p53. cyclin A1-/- cells showed increased radiosensitivity. To unravel
      a potential role of cyclin A1 in DNA repair, we performed a yeast triple hybrid
      screen and identified the Ku70 DNA repair protein as a binding partner and
      substrate of the cyclin A1-CDK2 complex. DNA double-strand break (DSB) repair was
      deficient in cyclin A1-/- cells. Further experiments indicated that A-type
      cyclins activate DNA DSB repair by mechanisms that depend on CDK2 activity and Ku
      proteins. Both cyclin A1 and cyclin A2 enhanced DSB repair by homologous
      recombination, but only cyclin A1 significantly activated nonhomologous end
      joining. DNA DSB repair was specific for A-type cyclins because cyclin E was
      ineffective. These findings establish a novel function for cyclin A1 and CDK2 in
      DNA DSB repair following radiation damage.

PMID- 15456867
TI  - beta-arrestin-1 competitively inhibits insulin-induced ubiquitination and
      degradation of insulin receptor substrate 1.
AB  - beta-arrestin-1 is an adaptor protein that mediates agonist-dependent
      internalization and desensitization of G-protein-coupled receptors (GPCRs) and
      also participates in the process of heterologous desensitization between receptor
      tyrosine kinases and GPCR signaling. In the present study, we determined whether
      beta-arrestin-1 is involved in insulin-induced insulin receptor substrate 1 (IRS
      1) degradation. Overexpression of wild-type (WT) beta-arrestin-1 attenuated
      insulin-induced degradation of IRS-1, leading to increased insulin signaling
      downstream of IRS-1. When endogenous beta-arrestin-1 was knocked down by
      transfection of beta-arrestin-1 small interfering RNA, insulin-induced IRS-1
      degradation was enhanced. Insulin stimulated the association of IRS-1 and Mdm2,
      an E3 ubiquitin ligase, and this association was inhibited to overexpression of
      WT beta-arrestin-1, which led by decreased ubiquitin content of IRS-1, suggesting
      that both beta-arrestin-1 and IRS-1 competitively bind to Mdm2. In summary, we
      have found the following: (i) beta-arrestin-1 can alter insulin signaling by
      inhibiting insulin-induced proteasomal degradation of IRS-1; (ii) beta-arrestin-1
      decreases the rate of ubiquitination of IRS-1 by competitively binding to
      endogenous Mdm2, an E3 ligase that can ubiquitinate IRS-1; (iii)
      dephosphorylation of S412 on beta-arrestin and the amino terminus of beta
      arrestin-1 are required for this effect of beta-arrestin on IRS-1 degradation;
      and (iv) inhibition of beta-arrestin-1 leads to enhanced IRS-1 degradation and
      accentuated cellular insulin resistance.

PMID- 15456868
TI  - The interaction between Sgt1p and Skp1p is regulated by HSP90 chaperones and is
      required for proper CBF3 assembly.
AB  - Sgt1p is a well-conserved protein proposed to be involved in a number of cellular
      processes. Genetic studies of budding yeast suggest a role for SGT1 in signal
      transduction, cell cycle advance, and chromosome segregation. Recent evidence has
      linked Sgt1p to HSP90 chaperones, although the precise relationship between these
      proteins is unclear. To further explore the role of Sgt1p in these processes, we
      have characterized the interactions among Sgt1p, the inner kinetochore complex
      CBF3, and HSP90 chaperones. We show that the amino terminus of Sgt1p interacts
      with CBF3 subunits Skp1p and Ctf13p. HSP90 interacts with Sgt1p and, in
      combination with the carboxy terminus of Sgt1p, regulates the interaction between
      Sgt1p and Skp1p in a nucleotide-dependent manner. While the Sgt1p-Skp1p
      interaction is required for CBF3 assembly, mutations that stabilize this
      interaction prevent the turnover of protein complexes important for CBF3
      assembly. We propose that HSP90 and Sgt1p act together as a molecular switch,
      maintaining transient interactions required to balance protein complex assembly
      with turnover.

PMID- 15456869
TI  - Notch-induced E2A degradation requires CHIP and Hsc70 as novel facilitators of
      ubiquitination.
AB  - E2A transcription factors, E12 and E47, are important regulators of lymphocyte
      development. Notch signaling pathways have been shown to regulate E2A function by
      accelerating the degradation of E2A proteins through a mitogen-activated protein
      kinase-dependent and ubiquitin-mediated pathway. To further understand the
      mechanism underlying E2A ubiquitination and degradation, we conducted a yeast two
      hybrid screen and identified the carboxyl terminus of Hsc70-interacting protein
      (CHIP) as an E47 binding protein. Here, we show that CHIP associates with E2A
      proteins in vivo and that overexpression of CHIP induces E47 degradation in a
      phosphorylation-dependent manner. Conversely, knocking down CHIP with small
      interfering RNA alleviates Notch-induced E47 degradation. CHIP binds E47 through
      the E protein homology domains 2 and 3 (EHD2 and EHD3). This interaction between
      CHIP and E47 is independent of the U-box domain with E3 ubiquitin ligase activity
      but requires the chaperone binding tetratricopeptide repeats domain. The ability
      of CHIP to induce E47 ubiquitination and degradation correlates with its ability
      to bind E47. We propose that CHIP, together with its partner Hsc70, forms a
      preubiquitination complex (PUC) with E47 and Skp2, thus facilitating the
      interaction between E47 and Skp2. CHIP also associates with Cul1, which
      introduces PUC to the SCF E3 ligase complex, responsible for E47 ubiquitination.
      Therefore, CHIP plays a crucial role in the ubiquitination and degradation of E2A
      proteins.

PMID- 15456870
TI  - RNA polymerase II carboxy-terminal domain phosphorylation is required for
      cotranscriptional pre-mRNA splicing and 3'-end formation.
AB  - We investigated the role of RNA polymerase II (pol II) carboxy-terminal domain
      (CTD) phosphorylation in pre-mRNA processing coupled and uncoupled from
      transcription in Xenopus oocytes. Inhibition of CTD phosphorylation by the kinase
      inhibitors 5,6-dichloro-1beta-D-ribofuranosyl-benzimidazole and H8 blocked
      transcription-coupled splicing and poly(A) site cleavage. These experiments
      suggest that pol II CTD phosphorylation is required for efficient pre-mRNA
      splicing and 3'-end formation in vivo. In contrast, processing of injected pre
      mRNA was unaffected by either kinase inhibitors or alpha-amanitin-induced
      depletion of pol II. pol II therefore does not appear to participate directly in
      posttranscriptional processing, at least in frog oocytes. Together these
      experiments show that the influence of the phosphorylated CTD on pre-mRNA
      splicing and 3'-end processing is mediated by transcriptional coupling.

PMID- 15456871
TI  - Glycogen synthase kinase 3 phosphorylates RBL2/p130 during quiescence.
AB  - Phosphorylation of the retinoblastoma-related or pocket proteins RB1/pRb,
      RBL1/p107, and RBL2/p130 regulates cell cycle progression and exit. While all
      pocket proteins are phosphorylated by cyclin-dependent kinases (CDKs) during the
      G1/S-phase transition, p130 is also specifically phosphorylated in G0-arrested
      cells. We have previously identified several phosphorylated residues that match
      the consensus site for glycogen synthase kinase 3 (GSK3) in the G0 form of p130.
      Using small-molecule inhibitors of GSK3, site-specific mutants of p130, and
      phospho-specific antibodies, we demonstrate here that GSK3 phosphorylates p130
      during G0. Phosphorylation of p130 by GSK3 contributes to the stability of p130
      but does not affect its ability to interact with E2F4 or cyclins. Regulation of
      p130 by GSK3 provides a novel link between growth factor signaling and regulation
      of the cell cycle progression and exit.

PMID- 15456872
TI  - Alix/AIP1 antagonizes epidermal growth factor receptor downregulation by the Cbl
      SETA/CIN85 complex.
AB  - The assembly of the Cbl-SETA/CIN85-endophilin complex at the C terminus of the
      epidermal growth factor receptor (EGFR) following ligand activation mediates its
      internalization and ubiquitination. We found that the SETA/CIN85-interacting
      protein Alix/AIP1, which also binds endophilins, modulates this complex. Alix was
      found to associate indirectly with EGFR, regardless of its activation state, and
      with DeltaEGFR, which signals at low intensity and does not bind Cbls or
      SETA/CIN85. In agreement with this, Alix interaction did not occur via
      SETA/CIN85. However, SETA/CIN85 and Alix were capable of mutually promoting their
      interaction with the EGFR. Increasing the level of Alix weakened the interaction
      between SETA/CIN85 and Cbl and reduced the tyrosine phosphorylation of c-Cbl and
      the level of ubiquitination of EGFR, SETA/CIN85, and Cbls. This antagonism of the
      Cbl-SETA/CIN85 complex by Alix was reflected in its diminution of EGFR
      internalization. In agreement with this, small interfering RNA-mediated knockdown
      of Alix promoted EGFR internalization and downregulation. It has been suggested
      that SETA/CIN85 promotes receptor internalization by recruiting endophilins.
      However, Alix was also capable of increasing the level of endophilin associated
      with EGFR, implying that this is not sufficient to promote receptor
      internalization. We propose that Alix inhibits EGFR internalization by
      attenuating the interaction between Cbl and SETA/CIN85 and by inhibiting Cbl
      mediated ubiquitination of the EGFR.

PMID- 15456873
TI  - Regulation and recognition of SCFGrr1 targets in the glucose and amino acid
      signaling pathways.
AB  - SCFGrr1, one of several members of the SCF family of E3 ubiquitin ligases in
      budding Saccharomyces cerevisiae, is required for both regulation of the cell
      cycle and nutritionally controlled transcription. In addition to its role in
      degradation of Gic2 and the CDK targets Cln1 and Cln2, Grr1 is also required for
      induction of glucose- and amino acid-regulated genes. Induction of HXT genes by
      glucose requires the Grr1-dependent degradation of Mth1. We show that Mth1 is
      ubiquitinated in vivo and degraded via the proteasome. Furthermore,
      phosphorylated Mth1, targeted by the casein kinases Yck1/2, binds to Grr1. That
      binding depends upon the Grr1 leucine-rich repeat (LRR) domain but not upon the F
      box or basic residues within the LRR that are required for recognition of Cln2
      and Gic2. Those observations extend to a large number of Grr1-dependent genes,
      some targets of the amino acid-regulated SPS signaling system, which are properly
      regulated in the absence of those basic LRR residues. Finally, we show that
      regulation of the SPS targets requires the Yck1/2 casein kinases. We propose that
      casein kinase I plays a similar role in both nutritional signaling pathways by
      phosphorylating pathway components and targeting them for ubiquitination by
      SCFGrr1.

PMID- 15456874
TI  - c-Jun-deficient cells undergo premature senescence as a result of spontaneous DNA
      damage accumulation.
AB  - Mouse embryo fibroblasts deficient for the c-Jun proto-oncogene (c-Jun-/- MEF)
      undergo p53-dependent premature senescence in conventional culture. This
      phenotype becomes evident only after several cell divisions, suggesting that
      senescence may result from exposure to unknown environmental factors. Here, we
      show that c-Jun-/- MEF can proliferate successfully in low oxygen (3% O2),
      indicating that premature senescence under conventional culture conditions is a
      consequence of hyperoxic stress. c-Jun-/- MEF exhibit higher basal levels of DNA
      damage compared to normal fibroblasts in high but not low oxygen, implying that
      senescence results from chronic accumulation of spontaneous DNA damage. This
      accumulation may be attributable, at least in part, to inefficient repair, since
      DNA damage induced by gamma ionizing radiation and H2O2 persists for longer in c
      Jun-/- MEF than in wild-type MEF. Unexpectedly, p53 expression, phosphorylation,
      and transcriptional activity are largely unaffected by oxygen exposure,
      indicating that the accumulation of spontaneous DNA damage does not result in
      chronic activation of p53 as judged by conventional criteria. Finally, we find
      that c-Jun associates with nuclear foci containing gammaH2AX and ATM following
      irradiation, suggesting a potential role for c-Jun in DNA repair processes per
      se.

PMID- 15456875
TI  - Genetically increasing Myoc expression supports a necessary pathologic role of
      abnormal proteins in glaucoma.
AB  - Despite the importance of MYOC for glaucoma, the protein's normal function(s) and
      the pathogenic mechanism(s) of MYOC mutations are not clear. Elevated intraocular
      pressure (IOP) and glaucoma are sometimes induced by corticosteroids, and
      corticosteroid use can result in substantially increased MYOC expression. It has
      been suggested, therefore, that steroid-induced MYOC protein levels cause steroid
      induced glaucoma and that protein level-increasing mutations in MYOC contribute
      to glaucoma not associated with steroid use. A causative role of elevated MYOC
      levels in steroid-induced glaucoma is controversial, however, and it is not clear
      if elevated MYOC levels can result in IOP elevation. To directly test if
      increased levels of MYOC can cause IOP elevation and glaucoma, we generated
      bacterial artificial chromosome transgenic mice that overexpress Myoc at a level
      similar to that induced by corticosteroid use. These mice do not develop elevated
      IOP or glaucoma. Our present findings, along with the absence of glaucoma in mice
      completely lacking MYOC, show that changing the level of MYOC is not pathogenic
      (from absent to approximately 15 times normal). These findings suggest that
      noncoding sequence variants are unlikely to influence glaucoma and that disease
      pathogenesis in primary open-angle glaucoma patients is dependent upon the
      expression of abnormal mutant proteins. This work does not support a causative
      role for increased MYOC levels or the MYOC gene in steroid-induced glaucoma.

PMID- 15456876
TI  - Transgenic analysis reveals that thyroid hormone receptor is sufficient to
      mediate the thyroid hormone signal in frog metamorphosis.
AB  - Thyroid hormone (T3) has long been known to be important for vertebrate
      development and adult organ function. Whereas thyroid hormone receptor (TR)
      knockout and transgenic studies of mice have implicated TR involvement in
      mammalian development, the underlying molecular bases for the resulting
      phenotypes remain to be determined in vivo, especially considering that T3 is
      known to have both genomic, i.e., through TRs, and nongenomic effects on cells.
      Amphibian metamorphosis is an excellent model for studying the role of TR in
      vertebrate development because of its total dependence on T3. Here we
      investigated the role of TR in metamorphosis by developing a dominant positive
      mutant thyroid hormone receptor (dpTR). In the frog oocyte transcription system,
      dpTR bound a T3-responsive promoter and activated the promoter independently of
      T3. Transgenic expression of dpTR under the control of a heat shock-inducible
      promoter in premetamorphic tadpoles led to precocious metamorphic
      transformations. Molecular analyses showed that dpTR induced metamorphosis by
      specifically binding to known T3 target genes, leading to increased local histone
      acetylation and gene activation, similar to T3-bound TR during natural
      metamorphosis. Our experiments indicated that the metamorphic role of T3 is
      through genomic action of the hormone, at least on the developmental parameters
      tested. They further provide the first example where TR is shown to mediate
      directly and sufficiently these developmental effects of T3 in individual organs
      by regulating target gene expression in these organs.

PMID- 15456877
TI  - Vhlh gene deletion induces Hif-1-mediated cell death in thymocytes.
AB  - The von Hippel-Lindau gene product (pVHL) targets the alpha subunit of basic
      helix-loop-helix transcription factor hypoxia-inducible factor (HIF) for
      proteasomal degradation. Inactivation of pVhl in the mouse germ line results in
      embryonic lethality, indicating that tight control of Hif-mediated adaptive
      responses to hypoxia is required for normal development and tissue function. In
      order to investigate the role of pVhl in T-cell development, we generated mice
      with thymocyte-specific inactivation of Vhlh resulting in constitutive
      transcriptional activity of Hif-1, as well as mice with thymocyte-specific
      repression of Hif-1 in a wild-type and Vhlh-deficient background. Thymi from Vhlh
      deficient mice were small due to a severe reduction in the total number of
      CD4/CD8-double-positive thymocytes which was associated with increased apoptosis
      in vivo and in vitro. Increased apoptosis was a result of enhanced caspase 8
      activity, while Bcl-2 and Bcl-XL transgene expression had little effect on this
      phenotype. Inactivation of Hif-1 in Vhlh-deficient thymocytes restored thymic
      cellularity as well as thymocyte viability in vitro. Our data suggest that tight
      regulation of Hif-1 via pVhl is required for normal thymocyte development and
      viability and that an increase in Hif-1 transcriptional activity enhances caspase
      8-mediated apoptosis in thymocytes.

PMID- 15456878
TI  - The PWWP domain of Dnmt3a and Dnmt3b is required for directing DNA methylation to
      the major satellite repeats at pericentric heterochromatin.
AB  - Dnmt3a and Dnmt3b are responsible for the establishment of DNA methylation
      patterns during development. These proteins contain, in addition to a C-terminal
      catalytic domain, a unique N-terminal regulatory region that harbors conserved
      domains, including a PWWP domain. The PWWP domain, characterized by the presence
      of a highly conserved proline-tryptophan-tryptophan-proline motif, is a module of
      100 to 150 amino acids found in many chromatin-associated proteins. However, the
      function of the PWWP domain remains largely unknown. In this study, we provide
      evidence that the PWWP domains of Dnmt3a and Dnmt3b are involved in functional
      specialization of these enzymes. We show that both endogenous and green
      fluorescent protein-tagged Dnmt3a and Dnmt3b are particularly concentrated in
      pericentric heterochromatin. Mutagenesis analysis indicates that their PWWP
      domains are required for their association with pericentric heterochromatin.
      Disruption of the PWWP domain abolishes the ability of Dnmt3a and Dnmt3b to
      methylate the major satellite repeats at pericentric heterochromatin.
      Furthermore, we demonstrate that the Dnmt3a PWWP domain has little DNA-binding
      ability, in contrast to the Dnmt3b PWWP domain, which binds DNA nonspecifically.
      Collectively, our results suggest that the PWWP domains of Dnmt3a and Dnmt3b are
      essential for targeting these enzymes to pericentric heterochromatin, probably
      via a mechanism other than protein-DNA interactions.

PMID- 15456879
TI  - Bromodomain protein Brd4 binds to GTPase-activating SPA-1, modulating its
      activity and subcellular localization.
AB  - Brd4 is a mammalian protein that contains a double bromodomain. It binds to
      chromatin and regulates cell cycle progression at multiple stages. By
      immunopurification and mass spectrometry, we identified a Rap GTPase-activating
      protein (GAP), signal-induced proliferation-associated protein 1 (SPA-1), as a
      factor that interacts with Brd4. SPA-1 localizes to the cytoplasm and to a lesser
      degree in the nucleus, while Brd4 resides in the nucleus. Bifluorescence
      complementation revealed that Brd4 and SPA-1 interact with each other in the
      nucleus of living cells. Supporting the functional importance of the interaction,
      Brd4 enhanced Rap GAP activity of SPA-1. Furthermore ectopic expression of SPA-1
      and Brd4 redirected subcellular localization of the partner and disrupted normal
      cell cycle progression. These effects were, however, reversed by coexpression of
      the two proteins, indicating that a proper balance between Brd4 and SPA-1 in G2
      is required for cell division. This work reveals a novel link between Brd4 and a
      GTPase-dependent mitogenic signaling pathway.

PMID- 15456880
TI  - nor-1 regulates hippocampal axon guidance, pyramidal cell survival, and seizure
      susceptibility.
AB  - The nuclear receptor transcription factor, nor-1, is expressed during mammalian
      development predominantly in the nervous system and is induced in a cell-specific
      manner in nonneuronal cells in response to a variety of extracellular stimuli. To
      elucidate the essential developmental functions of this transcription factor, we
      have analyzed the consequences of its elimination on central nervous system
      development in mice. Here we show that null mutant mice lacking nor-1 respond
      with increased limbic seizure activity to the excitotoxic glutamate receptor
      agonist kainic acid. We demonstrate that these abnormalities are associated with
      defective postnatal hippocampal development exemplified by abnormal axonal
      guidance of dentate gyrus granule and mossy cells, disorganization of the
      pyramidal cell layer, and early postnatal death of pyramidal neurons in the CA1
      field of the hippocampus. Our data indicate that nor-1 plays a critical role in
      neuronal survival and axonal guidance in the developing murine hippocampus and
      that hippocampal dysgenesis in nor-1-/- mice may be an underlying cause of
      seizure susceptibility.

PMID- 15456881
TI  - Estrogen-related receptor alpha directs peroxisome proliferator-activated
      receptor alpha signaling in the transcriptional control of energy metabolism in
      cardiac and skeletal muscle.
AB  - Estrogen-related receptors (ERRs) are orphan nuclear receptors activated by the
      transcriptional coactivator peroxisome proliferator-activated receptor gamma
      (PPARgamma) coactivator 1alpha (PGC-1alpha), a critical regulator of cellular
      energy metabolism. However, metabolic target genes downstream of ERRalpha have
      not been well defined. To identify ERRalpha-regulated pathways in tissues with
      high energy demand such as the heart, gene expression profiling was performed
      with primary neonatal cardiac myocytes overexpressing ERRalpha. ERRalpha
      upregulated a subset of PGC-1alpha target genes involved in multiple energy
      production pathways, including cellular fatty acid transport, mitochondrial and
      peroxisomal fatty acid oxidation, and mitochondrial respiration. These results
      were validated by independent analyses in cardiac myocytes, C2C12 myotubes, and
      cardiac and skeletal muscle of ERRalpha-/- mice. Consistent with the gene
      expression results, ERRalpha increased myocyte lipid accumulation and fatty acid
      oxidation rates. Many of the genes regulated by ERRalpha are known targets for
      the nuclear receptor PPARalpha, and therefore, the interaction between these
      regulatory pathways was explored. ERRalpha activated PPARalpha gene expression
      via direct binding of ERRalpha to the PPARalpha gene promoter. Furthermore, in
      fibroblasts null for PPARalpha and ERRalpha, the ability of ERRalpha to activate
      several PPARalpha targets and to increase cellular fatty acid oxidation rates was
      abolished. PGC-1alpha was also shown to activate ERRalpha gene expression. We
      conclude that ERRalpha serves as a critical nodal point in the regulatory
      circuitry downstream of PGC-1alpha to direct the transcription of genes involved
      in mitochondrial energy-producing pathways in cardiac and skeletal muscle.

PMID- 15456882
TI  - SOCS-1 localizes to the microtubule organizing complex-associated 20S proteasome.
AB  - The regulation of cytokine signaling is critical for controlling cellular
      proliferation and activation during an immune response. SOCS-1 is a potent
      inhibitor of Jak kinase activity and of signaling initiated by several cytokines.
      SOCS-1 protein levels are tightly regulated, and recent data suggest that SOCS-1
      may regulate the protein levels of some signaling proteins by the ubiquitin
      proteasome pathway; however, the cellular mechanism by which SOCS-1 directs
      proteins for degradation is unknown. In this report, SOCS-1 is found to
      colocalize and biochemically copurify with the microtubule organizing complex
      (MTOC) and its associated 20S proteasome. The SOCS-1 SH2 domain is required for
      the localization of SOCS-1 to the MTOC. Overexpression of SOCS-1 targets Jak1 in
      an SH2-dependent manner to a perinuclear distribution resembling the MTOC
      associated 20S proteasome. Analysis of MTOCs fractionated from SOCS-1-deficient
      cells demonstrates that SOCS-1 may function redundantly to regulate the
      localization of Jak1 to the MTOC. Nocodazole inhibits the protein turnover of
      SOCS-1, demonstrating that the minus-end transport of SOCS-1 to the MTOC
      associated 20S proteasome is required to regulate SOCS-1 protein levels. These
      data link SOCS-1 directly with the proteasome pathway and suggest another
      function for the SH2 domain of SOCS-1 in the regulation of Jak/STAT signaling.

PMID- 15456883
TI  - Phosphatidylinositol-4,5-bisphosphate-rich plasma membrane patches organize
      active zones of endocytosis and ruffling in cultured adipocytes.
AB  - A major regulator of endocytosis and cortical F-actin is thought to be
      phosphatidylinositol-4,5-bisphosphate [PtdIns(4,5)P2] present in plasma
      membranes. Here we report that in 3T3-L1 adipocytes, clathrin-coated membrane
      retrieval and dense concentrations of polymerized actin occur in restricted zones
      of high endocytic activity. Ultrafast-acquisition and superresolution
      deconvolution microscopy of cultured adipocytes expressing an enhanced green
      fluorescent protein- or enhanced cyan fluorescent protein (ECFP)-tagged
      phospholipase Cdelta1 (PLCdelta1) pleckstrin homology (PH) domain reveals that
      these zones spatially coincide with large-scale PtdIns(4,5)P2-rich plasma
      membrane patches (PRMPs). PRMPs exhibit lateral dimensions exceeding several
      micrometers, are relatively stationary, and display extensive local membrane
      folding that concentrates PtdIns(4,5)P2 in three-dimensional space. In addition,
      a higher concentration of PtdIns(4,5)P2 in the membranes of PRMPs than in other
      regions of the plasma membrane can be detected by quantitative fluorescence
      microscopy. Vesicular structures containing both clathrin heavy chains and
      PtdIns(4,5)P2 are revealed immediately beneath PRMPs, as is dense F actin.
      Blockade of PtdIns(4,5)P2 function in PRMPs by high expression of the ECFP-tagged
      PLCdelta1 PH domain inhibits transferrin endocytosis and reduces the abundance of
      cortical F-actin. Membrane ruffles induced by the expression of unconventional
      myosin 1c were also found to localize at PRMPs. These results are consistent with
      the hypothesis that PRMPs organize active PtdIns(4,5)P2 signaling zones in the
      adipocyte plasma membrane that in turn control regulators of endocytosis, actin
      dynamics, and membrane ruffling.

PMID- 15456884
TI  - p55, the Drosophila ortholog of RbAp46/RbAp48, is required for the repression of
      dE2F2/RBF-regulated genes.
AB  - Many proteins have been proposed to be involved in retinoblastoma protein (pRB)
      mediated repression, but it is largely uncertain which cofactors are essential
      for pRB to repress endogenous E2F-regulated promoters. Here we have taken
      advantage of the stream-lined Drosophila dE2F/RBF pathway, which has only two
      E2Fs (dE2F1 and dE2F2), and two pRB family members (RBF1 and RBF2). With RNA
      interference (RNAi), we depleted potential corepressors and looked for the
      elevated expression of groups of E2F target genes that are known to be directly
      regulated by RBF1 and RBF2. Previous studies have implicated histone deacetylase
      (HDAC) and SWI/SNF chromatin-modifying complexes in pRB-mediated repression.
      However, our results fail to support the idea that the SWI/SNF proteins are
      required for RBF-mediated repression and suggest that a requirement for HDAC
      activities is likely to be limited to a subset of targets. We found that the
      chromatin assembly factor p55/dCAF-1 is essential for the repression of dE2F2
      regulated targets. The removal of p55 deregulated the expression of E2F targets
      that are normally repressed by dE2F2/RBF1 and dE2F2/RBF2 complexes in a cell
      cycle-independent manner but had no effect on the expression of E2F targets that
      are normally coupled with cell proliferation. The results indicate that the
      mechanisms of RBF regulation at these two types of E2F targets are different and
      suggest that p55, and perhaps p55's mammalian orthologs RbAp46 and RbAp48, have a
      conserved function in repression by pRB-related proteins.

PMID- 15456885
TI  - PHR1, a PH domain-containing protein expressed in primary sensory neurons.
AB  - Previously, we identified PHR1 as an abundantly expressed gene in photoreceptors
      and showed that it encodes four isoforms, each with N-terminal pleckstrin
      homology (PH) and C-terminal transmembrane domains. To better understand PHR1
      function and expression, we made a Phr1 null mouse by inserting a beta
      galactosidase/neor cassette into exon 3. In addition to photoreceptors, we found
      abundant expression of specific Phr1 splice forms in olfactory receptor neurons
      and vestibular and cochlear hair cells. We also found Phr1 expression in cells
      with a possible sensory function, including peripheral retinal ganglion cells,
      cochlear interdental cells, and neurons of the circumventricular organ. Despite
      this discrete expression in known and putative sensory neurons, mice lacking PHR1
      do not have overt sensory deficits.

PMID- 15456886
TI  - Comparison of ABF1 and RAP1 in chromatin opening and transactivator potentiation
      in the budding yeast Saccharomyces cerevisiae.
AB  - Autonomously replicating sequence binding factor 1 (ABF1) and repressor/activator
      protein 1 (RAP1) from budding yeast are multifunctional, site-specific DNA
      binding proteins, with roles in gene activation and repression, replication, and
      telomere structure and function. Previously we have shown that RAP1 can prevent
      nucleosome positioning in the vicinity of its binding site and have provided
      evidence that this ability to create a local region of "open" chromatin
      contributes to RAP1 function at the HIS4 promoter by facilitating binding and
      activation by GCN4. Here we examine and directly compare to that of RAP1 the
      ability of ABF1 to create a region of open chromatin near its binding site and to
      contribute to activated transcription at the HIS4, ADE5,7, and HIS7 promoters.
      ABF1 behaves similarly to RAP1 in these assays, but it shows some subtle
      differences from RAP1 in the character of the open chromatin region near its
      binding site. Furthermore, although the two factors can similarly enhance
      activated transcription at the promoters tested, RAP1 binding is continuously
      required for this enhancement, but ABF1 binding is not. These results indicate
      that ABF1 and RAP1 achieve functional similarity in part via mechanistically
      distinct pathways.

PMID- 15456887
TI  - Germinal center kinase is required for optimal Jun N-terminal kinase activation
      by Toll-like receptor agonists and is regulated by the ubiquitin proteasome
      system and agonist-induced, TRAF6-dependent stabilization.
AB  - Germinal center kinase (GCK), a member of the Ste20 family, selectively activates
      the Jun N-terminal kinase (JNK) group of mitogen-activated protein kinases. Here,
      we show that endogenous GCK is activated by polyinosine-polycytidine [poly(IC)]
      and lipopolysaccharides (LPS), lipid A, interleukin-1 (IL-1), and engagement of
      CD40, all agonists that require TRAF6 for JNK activation. RNA interference
      experiments indicate that GCK is required for the maximal activation of JNK by
      LPS, lipid A, poly(IC), and, to a lesser extent, IL-1 and engagement of CD40. GCK
      is ubiquitinated in situ and stabilized by inhibitors of the proteasome,
      indicating that GCK is subject to proteasomal turnover. GCK is constitutively
      active, and the kinase activity of GCK is required for GCK ubiquitination.
      Agonist activation of GCK involves the TRAF6-dependent transient stabilization of
      the GCK polypeptide rather than an increase in intrinsic kinase activity. Our
      results identify a physiologic function and unexpected mode of regulation for
      GCK.

PMID- 15456888
TI  - The WW domain-containing proteins interact with the early spliceosome and
      participate in pre-mRNA splicing in vivo.
AB  - A growing body of evidence supports the coordination of mRNA synthesis and its
      subsequent processing events. Nuclear proteins harboring both WW and FF protein
      interaction modules bind to splicing factors as well as RNA polymerase II and may
      serve to link transcription with splicing. To understand how WW domains
      coordinate the assembly of splicing complexes, we used glutathione S-transferase
      fusions containing WW domains from CA150 or FBP11 in pull-down experiments with
      HeLa cell nuclear extract. The WW domains associate preferentially with the U2
      small nuclear ribonucleoprotein and with splicing factors SF1, U2AF, and
      components of the SF3 complex. Accordingly, WW domain-associating factors bind to
      the 3' part of a pre-mRNA to form a pre-spliceosome-like complex. We performed
      both in vitro and in vivo splicing assays to explore the role of WW/FF domain
      containing proteins in this process. However, although CA150 is associated with
      the spliceosome, it appears to be dispensable for splicing in vitro.
      Nevertheless, in vivo depletion of CA150 substantially reduced splicing
      efficiency of a reporter pre-mRNA. Moreover, overexpression of CA150 fragments
      containing both WW and FF domains activated splicing and modulated alternative
      exon selection, probably by facilitating 3' splice site recognition. Our results
      suggest an essential role of WW/FF domain-containing factors in pre-mRNA splicing
      that likely occurs in concert with transcription in vivo.

PMID- 15456890
TI  - The endothelial cell-specific antibody PAL-E identifies a secreted form of
      vimentin in the blood vasculature.
AB  - During mammalian vascular development, endothelial cells form a complex array of
      vessels that differ markedly in structure and function, but the molecular basis
      for this vascular complexity is poorly understood. Recent insights into
      endothelial diversity have come from the identification of molecular markers
      expressed on distinct endothelial cell populations. One such marker, the PAL-E
      antibody, has been used for almost 20 years to distinguish blood and lymphatic
      vessels, but the identity of the protein recognized by PAL-E has been unknown. In
      the present study we have used protein purification and tandem mass spectrometry
      analysis of tryptic peptides to identify the PAL-E antigen as a secreted form of
      vimentin. Vimentin has been well characterized as an intracellular intermediate
      filament protein expressed broadly in mesenchymal cells. In contrast, PAL-E
      reactive vimentin is secreted extracellularly, its synthesis is restricted to a
      distinct population of blood endothelial cells and activated macrophages, and PAL
      E-reactive vimentin is found in circulating human blood. PAL-E-reactive vimentin
      does not arise from an endothelial cell-specific mRNA transcript but is the
      product of cell-specific posttranslational modification. The PAL-E antibody
      therefore defines secretion of vimentin as a molecular distinction among
      endothelial cells and exposes a novel, extracellular role for vimentin in the
      blood vasculature.

PMID- 15456889
TI  - The ribosome-bound chaperones RAC and Ssb1/2p are required for accurate
      translation in Saccharomyces cerevisiae.
AB  - The chaperone homologs RAC (ribosome-associated complex) and Ssb1/2p are anchored
      to ribosomes; Ssb1/2p directly interacts with nascent polypeptides. The absence
      of RAC or Ssb1/2p results in a similar set of phenotypes, including
      hypersensitivity against the aminoglycoside paromomycin, which binds to the small
      ribosomal subunit and compromises the fidelity of translation. In order to
      understand this phenomenon we measured the frequency of translation termination
      and misincorporation in vivo and in vitro with a novel reporter system.
      Translational fidelity was impaired in the absence of functional RAC or Ssb1/2p,
      and the effect was further enhanced by paromomycin. The mutant strains suffered
      primarily from a defect in translation termination, while misincorporation was
      compromised to a lesser extent. Consistently, a low level of soluble translation
      termination factor Sup35p enhanced growth defects in the mutant strains. Based on
      the combined data we conclude that RAC and Ssb1/2p are crucial in maintaining
      translational fidelity beyond their postulated role as chaperones for nascent
      polypeptides.

PMID- 15456891
TI  - Artemis is a phosphorylation target of ATM and ATR and is involved in the G2/M
      DNA damage checkpoint response.
AB  - Mutations in Artemis in both humans and mice result in severe combined
      immunodeficiency due to a defect in V(D)J recombination. In addition, Artemis
      mutants are radiosensitive and chromosomally unstable, which has been attributed
      to a defect in nonhomologous end joining (NHEJ). We show here, however, that
      Artemis-depleted cell extracts are not defective in NHEJ and that Artemis
      deficient cells have normal repair kinetics of double-strand breaks after
      exposure to ionizing radiation (IR). Artemis is shown, however, to interact with
      known cell cycle checkpoint proteins and to be a phosphorylation target of the
      checkpoint kinase ATM or ATR after exposure of cells to IR or UV irradiation,
      respectively. Consistent with these findings, our results also show that Artemis
      is required for the maintenance of a normal DNA damage-induced G2/M cell cycle
      arrest. Artemis does not appear, however, to act either upstream or downstream of
      checkpoint kinase Chk1 or Chk2. These results define Artemis as having a
      checkpoint function and suggest that the radiosensitivity and chromosomal
      instability of Artemis-deficient cells may be due to defects in cell cycle
      responses after DNA damage.

PMID- 15456892
TI  - Persistent activation by constitutive Ste7 promotes Kss1-mediated invasive growth
      but fails to support Fus3-dependent mating in yeast.
AB  - Mitogen-activated protein kinase kinase kinase-Ste11 (MAPKKK-Ste11), MAPKK-Ste7,
      and MAPK-Kss1 mediate pheromone-induced mating differentiation and nutrient
      responsive invasive growth in Saccharomyces cerevisiae. The mating pathway also
      requires the scaffold-Ste5 and the additional MAPK-Fus3. One contribution to
      specificity in this system is thought to come from stimulus-dependent recruitment
      of the MAPK cascade to upstream activators that are unique to one or the other
      pathway. To test this premise, we asked if stimulus-independent signaling by
      constitutive Ste7 would lead to a loss of biological specificity. Instead, we
      found that constitutive Ste7 promotes invasion without supporting mating
      responses. This specificity occurs because constitutive Ste7 activates Kss1, but
      not Fus3, in vivo and promotes filamentation gene expression while suppressing
      mating gene expression. Differences in the ability of constitutive Ste7 variants
      to bind the MAPKs and Ste5 account for the selective activation of Kss1. These
      findings support the model that Fus3 activation in vivo requires binding to both
      Ste7 and the scaffold-Ste5 but that Kss1 activation is independent of Ste5. This
      scaffold-independent activation of Kss1 by constitutive Ste7 and the existence of
      mechanisms for pathway-specific promoter discrimination impose a unique
      developmental fate independently of any distinguishing external stimuli.

PMID- 15456893
TI  - Mutational analysis of the N-terminal DNA-binding domain of sleeping beauty
      transposase: critical residues for DNA binding and hyperactivity in mammalian
      cells.
AB  - The N-terminal domain of the Sleeping Beauty (SB) transposase mediates transposon
      DNA binding, subunit multimerization, and nuclear translocation in vertebrate
      cells. For this report, we studied the relative contributions of 95 different
      residues within this multifunctional domain by large-scale mutational analysis.
      We found that each of four amino acids (leucine 25, arginine 36, isoleucine 42,
      and glycine 59) contributes to DNA binding in the context of the N-terminal 123
      amino acids of SB transposase, as indicated by electrophoretic mobility shift
      analysis, and to functional activity of the full-length transposase, as
      determined by a quantitative HeLa cell-based transposition assay. Moreover, we
      show that amino acid substitutions within either the putative oligomerization
      domain (L11A, L18A, L25A, and L32A) or the nuclear localization signal (K104A and
      R105A) severely impair its ability to mediate DNA transposition in mammalian
      cells. In contrast, each of 10 single amino acid changes within the bipartite DNA
      binding domain is shown to greatly enhance SB's transpositional activity in
      mammalian cells. These hyperactive mutations functioned synergistically when
      combined and are shown to significantly improve transposase affinity for
      transposon end sequences. Finally, we show that enhanced DNA-binding activity
      results in improved cleavage kinetics, increased SB element mobilization from
      host cell chromosomes, and dramatically improved gene transfer capabilities of SB
      in vivo in mice. These studies provide important insights into vertebrate
      transposon biology and indicate that Sleeping Beauty can be readily improved for
      enhanced genetic research applications in mammals.

PMID- 15456894
TI  - Dlx3 transcriptional regulation of osteoblast differentiation: temporal
      recruitment of Msx2, Dlx3, and Dlx5 homeodomain proteins to chromatin of the
      osteocalcin gene.
AB  - Genetic studies show that Msx2 and Dlx5 homeodomain (HD) proteins support
      skeletal development, but null mutation of the closely related Dlx3 gene results
      in early embryonic lethality. Here we find that expression of Dlx3 in the mouse
      embryo is associated with new bone formation and regulation of osteoblast
      differentiation. Dlx3 is expressed in osteoblasts, and overexpression of Dlx3 in
      osteoprogenitor cells promotes, while specific knock-down of Dlx3 by RNA
      interference inhibits, induction of osteogenic markers. We characterized gene
      regulation by Dlx3 in relation to that of Msx2 and Dlx5 during osteoblast
      differentiation. Chromatin immunoprecipitation assays revealed a molecular switch
      in HD protein association with the bone-specific osteocalcin (OC) gene. The
      transcriptionally repressed OC gene was occupied by Msx2 in proliferating
      osteoblasts, while Dlx3, Dlx5, and Runx2 were recruited postproliferatively to
      initiate transcription. Dlx5 occupancy increased over Dlx3 in mature osteoblasts
      at the mineralization stage of differentiation, coincident with increased RNA
      polymerase II occupancy. Dlx3 protein-DNA interactions stimulated OC promoter
      activity, while Dlx3-Runx2 protein-protein interaction reduced Runx2-mediated
      transcription. Deletion analysis showed that the Dlx3 interacting domain of Runx2
      is from amino acids 376 to 432, which also include the transcriptionally active
      subnuclear targeting sequence (376 to 432). Thus, we provide cellular and
      molecular evidence for Dlx3 in regulating osteoprogenitor cell differentiation
      and for both positive and negative regulation of gene transcription. We propose
      that multiple HD proteins in osteoblasts constitute a regulatory network that
      mediates development of the bone phenotype through the sequential association of
      distinct HD proteins with promoter regulatory elements.

PMID- 15456895
TI  - Osprey: a comprehensive tool employing novel methods for the design of
      oligonucleotides for DNA sequencing and microarrays.
AB  - We have developed a software package called Osprey for the calculation of optimal
      oligonucleotides for DNA sequencing and the creation of microarrays based on
      either PCR-products or directly spotted oligomers. It incorporates a novel use of
      position-specific scoring matrices, for the sensitive and specific identification
      of secondary binding sites anywhere in the target sequence. Using accelerated
      hardware is faster and more efficient than the traditional pairwise alignments
      used in most oligo-design software. Osprey consists of a module for target site
      selection based on user input, novel utilities for dealing with problematic
      sequences such as repeats, and a common code base for the identification of
      optimal oligonucleotides from the target list. Overall, these improvements
      provide a program that, without major increases in run time, reflects current DNA
      thermodynamics models, improves specificity and reduces the user's data
      preprocessing and parameterization requirements. Using a TimeLogic hardware
      accelerator, we report up to 50-fold reduction in search time versus a linear
      search strategy. Target sites may be derived from computer analysis of DNA
      sequence assemblies in the case of sequencing efforts, or genome or EST analysis
      in the case of microarray development in both prokaryotes and eukaryotes.

PMID- 15456896
TI  - Induction of cyclooxygenase-2 overexpression in human gastric epithelial cells by
      Helicobacter pylori involves TLR2/TLR9 and c-Src-dependent nuclear factor-kappaB
      activation.
AB  - Gastric epithelial cells were incubated with a panel of clinical isolates of
      Helicobacter pylori, including nonulcer dyspepsia with gastritis (HS, n = 20),
      gastric ulcer (HU, n = 20), duodenal ulcer (HD, n = 21), and gastric cancer (HC,
      n = 20). HC strains induced a higher cyclooxygenase-2 (COX-2) expression than
      those from HS, HD, and HU. The bacterial virulence factors and the host cellular
      pathways were investigated. Virulence genes of iceA, vacA, babA2, cagA 3' repeat
      region, and hrgA failed to show any association with the disease status and COX-2
      expression. Methylation-specific polymerase chain reaction revealed HC strains
      not affecting the methylation status of COX-2 promoter. Nuclear factor (NF)
      kappaB, NF-interleukin 6, and cAMP response element were found to be involved in
      COX-2 induction. We explored a novel NF-kappaB activation pathway. The mutants of
      TLR2 and TLR9, but not TLR4, inhibited H. pylori-induced COX-2 promoter activity,
      and neutralizing antibodies for TLR2 and TLR9 abolished H. pylori-induced COX-2
      expression. Phosphatidylinositol-specific phospholipase C (PI-PLC), protein
      kinase C (PKC), and Src inhibitors inhibited COX-2 induction. The dominant
      negative mutants of NIK and various IkappaB kinase complexes, including IKKbeta
      (Y188F), IKKbeta (Y199F), and IKKbeta (FF), inhibited the COX-2 promoter
      activity. Phosphorylation of GST-IKKbeta (132-206) at Tyr188 and Tyr199 by c-Src
      was found after H. pylori infection. In summary, H. pylori induces COX-2
      expression via activations of NF-kappaB, NF-interleukin 6, the cAMP response
      element. In NF-kappaB activation, H. pylori acts through TLR2/TLR9 to activate
      both the cascade of PI-PLCgamma/PKCalpha/c-Src/IKKalpha/beta and the cascade of
      NIK/IKKalpha/beta, resulting in the IkappaBalpha degradation and the expression
      of COX-2 gene. The COX-2 overexpression may contribute to the carcinogenesis in
      patients colonized with these strains.

PMID- 15456897
TI  - Patterns of polymorphism and divergence from noncoding sequences of Drosophila
      melanogaster and D. simulans: evidence for nonequilibrium processes.
AB  - Despite the fact that D. melanogaster and D. simulans have been the central model
      system for molecular population genetics, few data are available for noncoding
      regions. Here, we present an analysis of population genetic data from intergenic
      regions and comparisons of these data to previously collected data from introns
      and exons. Polymorphisms and fixations were categorized as A/T to G/C or G/C to
      A/T changes and were polarized by inferring the ancestral state using both
      parsimony and maximum likelihood. Noncoding fixations in both D. melanogaster and
      D. simulans were consistent with equilibrium base-composition evolution. However,
      polarized noncoding polymorphisms, revealed a different pattern. Although A/T to
      G/C and G/C to A/T polymorphisms in D. simulans were consistent with equilibrium,
      we observed a highly significant dearth of A/T to G/C polymorphisms in D.
      melanogaster introns but not in intergenic sequences. Such data could be
      explained by recent evolution of mutational biases associated with transcription
      or by lineage-specific selection on base composition. These data reveal the
      complexity of evolutionary processes acting even on noncoding DNA in Drosophila.

PMID- 15456898
TI  - Genomic analysis of stationary-phase and exit in Saccharomyces cerevisiae: gene
      expression and identification of novel essential genes.
AB  - Most cells on earth exist in a quiescent state. In yeast, quiescence is induced
      by carbon starvation, and exit occurs when a carbon source becomes available. To
      understand how cells survive in, and exit from this state, mRNA abundance was
      examined using oligonucleotide-based microarrays and quantitative reverse
      transcription-polymerase chain reaction. Cells in stationary-phase cultures
      exhibited a coordinated response within 5-10 min of refeeding. Levels of >1800
      mRNAs increased dramatically (>or=64-fold), and a smaller group of stationary
      phase mRNAs decreased in abundance. Motif analysis of sequences upstream of genes
      clustered by VxInsight identified an overrepresentation of Rap1p and BUF (RPA)
      binding sites in genes whose mRNA levels rapidly increased during exit.
      Examination of 95 strains carrying deletions in stationary-phase genes induced
      identified 32 genes essential for survival in stationary-phase at 37 degrees C.
      Analysis of these genes suggests that mitochondrial function is critical for
      entry into stationary-phase and that posttranslational modifications and
      protection from oxidative stress become important later. The phylogenetic
      conservation of stationary-phase genes, and our findings that two-thirds of the
      essential stationary-phase genes have human homologues and of these, many have
      human homologues that are disease related, demonstrate that yeast is a bona fide
      model system for studying the quiescent state of eukaryotic cells.

PMID- 15456899
TI  - The endo-lysosomal sorting machinery interacts with the intermediate filament
      cytoskeleton.
AB  - Cytoskeletal networks control organelle subcellular distribution and function.
      Herein, we describe a previously unsuspected association between intermediate
      filament proteins and the adaptor complex AP-3. AP-3 and intermediate filament
      proteins cosedimented and coimmunoprecipitated as a complex free of microtubule
      and actin binding proteins. Genetic perturbation of the intermediate filament
      cytoskeleton triggered changes in the subcellular distribution of the adaptor AP
      3 and late endocytic/lysosome compartments. Concomitant with these architectural
      changes, and similarly to AP-3-null mocha cells, fibroblasts lacking vimentin
      were compromised in their vesicular zinc uptake, their organellar pH, and their
      total and surface content of AP-3 cargoes. However, the total content and surface
      levels, as well as the distribution of the transferrin receptor, a membrane
      protein whose sorting is AP-3 independent, remained unaltered in both AP-3- and
      vimentin-null cells. Based on the phenotypic convergence between AP-3 and
      vimentin deficiencies, we predicted and documented a reduced autophagosome
      content in mocha cells, a phenotype previously reported in cells with disrupted
      intermediate filament cytoskeletons. Our results reveal a novel role of the
      intermediate filament cytoskeleton in organelle/adaptor positioning and in
      regulation of the adaptor complex AP-3.

PMID- 15456900
TI  - Association of ARVCF with zonula occludens (ZO)-1 and ZO-2: binding to PDZ-domain
      proteins and cell-cell adhesion regulate plasma membrane and nuclear localization
      of ARVCF.
AB  - ARVCF, an armadillo-repeat protein of the p120(ctn) family, associates with
      classical cadherins and is present in adherens junctions, but its function is
      poorly understood. Here, we show that ARVCF interacts via a C-terminal PDZ
      binding motif with zonula occludens (ZO)-1 and ZO-2. ARVCF and ZO-1 partially
      colocalize in the vicinity of the apical adhesion complex in polarized epithelial
      Madin-Darby canine kidney cells. ARVCF, ZO-1, and E-cadherin form a complex and
      are recruited to sites of initial cell-cell contact in sparse cell cultures. E
      cadherin binding and plasma membrane localization of ARVCF require the PDZ
      binding motif. Disruption of cell-cell adhesion releases ARVCF from the plasma
      membrane and an increased fraction of the protein localizes to the nucleus.
      Nuclear localization of ARVCF also requires the PDZ-binding motif and can be
      mediated by the PDZ domains of ZO-2. Thus, the interaction of ARVCF with distinct
      PDZ-domain proteins determines its subcellular localization. Interactions with ZO
      1 and ZO-2, in particular, may mediate recruitment of ARVCF to the plasma
      membrane and the nucleus, respectively, possibly in response to cell-cell
      adhesion cues.

PMID- 15456901
TI  - Repeated cycles of rapid actin assembly and disassembly on epithelial cell
      phagosomes.
AB  - We have found that early in infection of the intracellular pathogen Listeria
      monocytogenes in Madin-Darby canine kidney epithelial cells expressing actin
      conjugated to green fluorescent protein, F-actin rapidly assembles (approximately
      25 s) and disassembles (approximately 30 s) around the bacteria, a phenomenon we
      call flashing. L. monocytogenes strains unable to perform actin-based motility or
      unable to escape the phagosome were capable of flashing, suggesting that the
      actin assembly occurs on the phagosome membrane. Cycles of actin assembly and
      disassembly could occur repeatedly on the same phagosome. Indirect
      immunofluorescence showed that most bacteria were fully internalized when
      flashing occurred, suggesting that actin flashing does not represent
      phagocytosis. Escherichia coli expressing invA, a gene product from Yersinia
      pseudotuberculosis that mediates cellular invasion, also induced flashing.
      Furthermore, polystyrene beads coated with E-cadherin or transferrin also induced
      flashing after internalization. This suggests that flashing occurs downstream of
      several distinct molecular entry mechanisms and may be a general consequence of
      internalization of large objects by epithelial cells.

PMID- 15456902
TI  - Distinct in vivo dynamics of vertebrate SUMO paralogues.
AB  - There are three mammalian SUMO paralogues: SUMO-1 is approximately 45% identical
      to SUMO-2 and SUMO-3, which are 96% identical to each other. It is currently
      unclear whether SUMO-1, -2, and -3 function in ways that are unique, redundant,
      or antagonistic. To address this question, we examined the dynamics of individual
      SUMO paralogues by using cell lines that stably express each of the mammalian
      SUMO proteins fused to the yellow fluorescent protein (YFP). Whereas SUMO-2 and 
      3 showed very similar distributions throughout the nucleoplasm, SUMO-1 was
      uniquely distributed to the nuclear envelope and to the nucleolus. Photobleaching
      experiments revealed that SUMO-1 dynamics was much slower than SUMO-2 and -3
      dynamics. Additionally, the mobility of SUMO paralogues differed between
      subnuclear structures. Finally, the timing and distributions were dissimilar
      between paralogues as cells exited from mitosis. SUMO-1 was recruited to nuclear
      membrane as nuclear envelopes reformed in late anaphase, and accumulated rapidly
      into the nucleus. SUMO-2 and SUMO-3 localized to chromosome earlier and
      accumulated gradually during telophase. Together, these findings demonstrate that
      mammalian SUMO-1 shows patterns of utilization that are clearly discrete from the
      patterns of SUMO-2 and -3 throughout the cell cycle, arguing that it is
      functionally distinct and specifically regulated in vivo.

PMID- 15456903
TI  - A Ddc2-Rad53 fusion protein can bypass the requirements for RAD9 and MRC1 in
      Rad53 activation.
AB  - Activation of Rad53p by DNA damage plays an essential role in DNA damage
      checkpoint pathways. Rad53p activation requires coupling of Rad53p to Mec1p
      through a "mediator" protein, Rad9p or Mrc1p. We sought to determine whether the
      mediator requirement could be circumvented by making fusion proteins between the
      Mec1 binding partner Ddc2p and Rad53p. Ddc2-Rad53p interacted with Mec1p and
      other Ddc2-Rad53p molecules under basal conditions and displayed an increased
      oligomerization upon DNA damage. Ddc2-Rad53p was activated in a Mec1p- and Tel1p
      dependent manner upon DNA damage. Expression of Ddc2-Rad53p in Deltarad9 or
      Deltarad9Deltamrc1 cells increased viability on plates containing the alkylating
      agent methyl methane sulfonate. Ddc2-Rad53p was activated at least partially by
      DNA damage in Deltarad9Deltamrc1 cells. In addition, expression of Ddc2-Rad53p in
      Deltarad24Deltarad17Deltamec3 cells increased cell survival. These results reveal
      minimal requirements for function of a core checkpoint signaling system.

PMID- 15456904
TI  - Construction, characterization, and complementation of a conditional-lethal DNA
      topoisomerase IIalpha mutant human cell line.
AB  - DNA Topoisomerase IIalpha (topoIIalpha) is a DNA decatenating enzyme, abundant
      constituent of mammalian mitotic chromosomes, and target of numerous antitumor
      drugs, but its exact role in chromosome structure and dynamics is unclear. In a
      powerful new approach to this important problem, with significant advantages over
      the use of topoII inhibitors or RNA interference, we have generated and
      characterized a human cell line (HTETOP) in which >99.5% topoIIalpha expression
      can be silenced in all cells by the addition of tetracycline. TopoIIalpha
      depleted HTETOP cells enter mitosis and undergo chromosome condensation, albeit
      with delayed kinetics, but normal anaphases and cytokineses are completely
      prevented, and all cells die, some becoming polyploid in the process. Cells can
      be rescued by expression of topoIIalpha fused to green fluorescent protein (GFP),
      even when certain phosphorylation sites have been mutated, but not when the
      catalytic residue Y805 is mutated. Thus, in addition to validating GFP-tagged
      topoIIalpha as an indicator for endogenous topoIIalpha dynamics, our analyses
      provide new evidence that topoIIalpha plays a largely redundant role in
      chromosome condensation, but an essential catalytic role in chromosome
      segregation that cannot be complemented by topoIIbeta and does not require
      phosphorylation at serine residues 1106, 1247, 1354, or 1393.

PMID- 15456906
TI  - Off with your (fork)head. One stress-defusing pathway shuts down another.

PMID- 15456905
TI  - Rab9 GTPase regulates late endosome size and requires effector interaction for
      its stability.
AB  - Rab9 GTPase resides in a late endosome microdomain together with mannose 6
      phosphate receptors (MPRs) and the tail-interacting protein of 47 kDa (TIP47). To
      explore the importance of Rab9 for microdomain establishment, we depleted the
      protein from cultured cells. Rab9 depletion decreased late endosome size and
      reduced the numbers of multilamellar and dense-tubule-containing late
      endosomes/lysosomes, but not multivesicular endosomes. The remaining late
      endosomes and lysosomes were more tightly clustered near the nucleus, implicating
      Rab9 in endosome localization. Cells displayed increased surface MPRs and
      lysosome-associated membrane protein 1. In addition, cells showed increased MPR
      synthesis in conjunction with MPR missorting to the lysosome. Surprisingly, Rab9
      stability on late endosomes required interaction with TIP47. Rabs are thought of
      as independent, prenylated entities that reside either on membranes or in
      cytosol, bound to GDP dissociation inhibitor. These data show that Rab9 stability
      is strongly influenced by a specific effector interaction. Moreover, Rab9 and the
      proteins with which it interacts seem critical for the maintenance of specific
      late endocytic compartments and endosome/lysosome localization.

PMID- 15456907
TI  - Knife jugglers. Painkillers shift Alzheimer's protein slicer.

PMID- 15456908
TI  - Ras: the other pro-aging pathway.
AB  - Studies in worms, flies, and mice point to the insulin/insulin-like growth factor
      1 (IGF-1)/phosphatidylinositol 3-kinase/Akt-like pathway as a central regulator
      of longevity. A similar pathway, which includes Sch9, a functional mammalian
      Akt/protein kinase B homolog, regulates longevity in yeast. Chronological aging
      in yeast is also regulated by a second pathway that includes Ras, adenylate
      cyclase, protein kinase A, the transcription factors Msn2 and Msn4, and Sod2.
      Although Ras proteins have not been implicated in longevity regulation in worms
      or flies, the major role of Ras in mammalian IGF-1 signaling raises the
      possibility that homologs of yeast Ras2 might accelerate aging in mammals. Here I
      review the data from experiments at both the organismal and cellular levels that
      support a role for Ras in the regulation of stress resistance and life span in
      eukaryotes.

PMID- 15456909
TI  - Creation and discovery of ligand-receptor pairs for transcriptional control with
      small molecules.
AB  - The nuclear receptor retinoid X receptor (RXR) is a ligand-activated
      transcription factor. To create receptors for a new ligand, a structure-based
      approach was used to generate a library of approximately 380,000 mutant RXR
      genes. To discover functional variants within the library, we used chemical
      complementation, a method of protein engineering that uses the power of genetic
      selection. Wild-type RXR has an EC50 of 500 nM for 9-cis retinoic acid (9cRA) and
      an EC50 of >10 microM for the synthetic retinoid-like compound LG335 in yeast.
      The library produced ligand-receptor pairs with LG335 that have a variety of EC50
      values (40 nM to >2 microM) and activation levels (10-80% of wild-type RXR with
      9cRA) in yeast. The variant I268V;A272V;I310L;F313M has an EC50 for LG335 of 40
      nM and an EC50 for 9cRA of >10 microM in yeast. This variant has essentially the
      reverse ligand specificity of wild-type RXR and is transcriptionally active at a
      10-fold-lower ligand concentration in yeast. This EC50 is 25-fold lower than the
      best receptor we have engineered through site-directed mutagenesis,
      Q275C;I310M;F313I. Furthermore, the variants' EC50 values and activation levels
      in yeast and mammalian cells correlate. This protein engineering method should be
      extendable to produce other functional ligand-receptor pairs, which can be
      selected and characterized from libraries within weeks. Coupling large library
      construction with chemical complementation could be used to engineer proteins
      that bind virtually any small molecule for conditional gene expression,
      applications in metabolic engineering, and biosensors and to engineer enzymes
      through genetic selection.

PMID- 15456910
TI  - Automated prediction of protein function and detection of functional sites from
      structure.
AB  - Current structural genomics projects are yielding structures for proteins whose
      functions are unknown. Accordingly, there is a pressing requirement for
      computational methods for function prediction. Here we present PHUNCTIONER, an
      automatic method for structure-based function prediction using automatically
      extracted functional sites (residues associated to functions). The method relates
      proteins with the same function through structural alignments and extracts 3D
      profiles of conserved residues. Functional features to train the method are
      extracted from the Gene Ontology (GO) database. The method extracts these
      features from the entire GO hierarchy and hence is applicable across the whole
      range of function specificity. 3D profiles associated with 121 GO annotations
      were extracted. We tested the power of the method both for the prediction of
      function and for the extraction of functional sites. The success of function
      prediction by our method was compared with the standard homology-based method. In
      the zone of low sequence similarity (approximately 15%), our method assigns the
      correct GO annotation in 90% of the protein structures considered, approximately
      20% higher than inheritance of function from the closest homologue.

PMID- 15456911
TI  - De novo design of conformationally flexible transmembrane peptides driving
      membrane fusion.
AB  - Fusion of biological membranes is mediated by distinct integral membrane
      proteins, e.g., soluble N-ethylmaleimide-sensitive factor attachment protein
      receptors and viral fusion proteins. Previous work has indicated that the
      transmembrane segments (TMSs) of such integral membrane proteins play an
      important role in fusion. Furthermore, peptide mimics of the transmembrane part
      can drive the fusion of liposomes, and evidence had been obtained that
      fusogenicity depends on their conformational flexibility. To test this
      hypothesis, we present a series of unnatural TMSs that were designed de novo
      based on the structural properties of hydrophobic residues. We find that the
      fusogenicity of these peptides depends on the ratio of alpha-helix-promoting Leu
      and beta-sheet-promoting Val residues and is enhanced by helix-destabilizing Pro
      and Gly residues within their hydrophobic cores. The ability of these peptides to
      refold from an alpha-helical state to a beta-sheet conformation and backwards was
      determined under different conditions. Membrane fusogenic peptides with mixed
      Leu/Val sequences tend to switch more readily between different conformations
      than a nonfusogenic peptide with an oligo-Leu core. We propose that structural
      flexibility of these TMSs is a prerequisite of fusogenicity.

PMID- 15456913
TI  - A proposed testing framework for developmental immunotoxicology (DIT).
AB  - A group of thirty immunotoxicology experts from the U.S. and E.U. representing
      government, industry, and academia met in May 2003, in Washington, D.C., to reach
      consensus regarding the most appropriate methods to assess developmental
      immunotoxicology (DIT) for hazard identification, including under what conditions
      such testing might be required. The following points represent the major
      conclusions from this roundtable discussion: (1) the rat is the preferred model;
      (2) any DIT protocol should be based on immune assays already validated; (3) DIT
      methods should be incorporated into standard developmental and reproductive
      toxicity protocols to the extent possible rather than a "stand-alone" protocol;
      (4) the approach to address DIT potential should be similar for chemicals and
      drugs, but the experimental design should be flexible and should reflect the
      specific questions to be answered; (5) it is possible to utilize a study design
      that assesses all critical windows in one protocol, with the results leading to
      further study of specific effects, as warranted; (6) animals should be exposed
      throughout the treatment protocol; (7) the triggers for DIT may include structure
      activity-relationships, results from other toxicity studies, the intended use of
      a drug/chemical and/or its anticipated exposure of neonates and/or juveniles.

PMID- 15456912
TI  - Erythropoietin mediates tissue protection through an erythropoietin and common
      beta-subunit heteroreceptor.
AB  - The cytokine erythropoietin (Epo) is tissue-protective in preclinical models of
      ischemic, traumatic, toxic, and inflammatory injuries. We have recently
      characterized Epo derivatives that do not bind to the Epo receptor (EpoR) yet are
      tissue-protective. For example, carbamylated Epo (CEpo) does not stimulate
      erythropoiesis, yet it prevents tissue injury in a wide variety of in vivo and in
      vitro models. These observations suggest that another receptor is responsible for
      the tissue-protective actions of Epo. Notably, prior investigation suggests that
      EpoR physically interacts with the common beta receptor (betacR), the signal
      transducing subunit shared by the granulocyte-macrophage colony stimulating
      factor, and the IL-3 and IL-5 receptors. However, because betacR knockout mice
      exhibit normal erythrocyte maturation, betacR is not required for erythropoiesis.
      We hypothesized that betacR in combination with the EpoR expressed by
      nonhematopoietic cells constitutes a tissue-protective receptor. In support of
      this hypothesis, membrane proteins prepared from rat brain, heart, liver, or
      kidney were greatly enriched in EpoR after passage over either Epo or CEpo
      columns but covalently bound in a complex with betacR. Further, antibodies
      against EpoR coimmunoprecipitated betacR from membranes prepared from neuronal
      like P-19 cells that respond to Epo-induced tissue protection. Immunocytochemical
      studies of spinal cord neurons and cardiomyocytes protected by Epo demonstrated
      cellular colocalization of Epo betacR and EpoR. Finally, as predicted by the
      hypothesis, neither Epo nor CEpo was active in cardiomyocyte or spinal cord
      injury models performed in the betacR knockout mouse. These data support the
      concept that EpoR and betacR comprise a tissue-protective heteroreceptor.

PMID- 15456914
TI  - The effect of a brominated flame retardant, tetrabromobisphenol-A, on free
      radical formation in human neutrophil granulocytes: the involvement of the MAP
      kinase pathway and protein kinase C.
AB  - This study investigates the effects of one of the most frequently used brominated
      flame-retardants (BFR), tetrabromobisphenol-A (TBBPA), on formation of reactive
      oxygen species (ROS) and calcium levels in human neutrophil granulocytes. TBBPA
      enhanced ROS production in a concentration-depended manner (1-12 microM),
      measured as 2,7-dichlorofluorescein diacetate amplified (DCF) fluorescence. The
      results on ROS production by TBBPA was confirmed by lucigenin-amplified
      chemiluminescence. The TBBPA induced formation of ROS was due to activation of
      respiratory burst, as shown by the NADPH oxidase inhibitor DPI (10 microM). TBBPA
      induced activation of respiratory burst was also inhibited by the MEK 1/2
      inhibitor U0126 (10 microM), the PKC inhibitor BIM (0.25 microM), and the
      tyrosine kinase inhibitor erbstatin-A (25 microM). We also found a small
      reduction in ROS formation in the absence of extracellular calcium and when
      verapamil was added. The phosphorylation of ERK 1/2 was confirmed by Western
      blotting. TBBPA also induced a concentration dependent increase in intracellular
      free calcium measured with Fura-2/AM. We suggest that exposure of human
      neutrophil granulocytes to the brominated flame retardant TBBPA leads to an
      activation of the NADPH oxidase primarily by an ERK 1/2 stimulated pathway. The
      data also show that PKC, calcium, and tyrosine kinases may be involved in the
      activation.

PMID- 15456915
TI  - Increased volume of the calbindin D28k-labeled sexually dimorphic hypothalamus in
      genistein and nonylphenol-treated male rats.
AB  - The adult rat brain develops through an interplay of neuronal proliferation and
      programmed cell death. Steroid hormones and growth factors may alter the balance
      between these competing processes. "Endocrine disrupters" (EDs) may also alter
      brain development, by mimicry or modulation of endogenous hormone systems. Under
      control conditions, the sexually dimorphic nucleus (SDN) of the medial preoptic
      hypothalamus becomes larger in adult males than females, but its final volume may
      also reflect the hormonal conditions prevailing during development. Two EDs that
      have recently been studied in protocols involving lifespan exposures are the
      phytoestrogen genistein and the weakly estrogenic compound para-nonylphenol,
      which is used in the production of many surfactants and plastics. Experimental
      dietary exposure of adult female rats to genistein or p-nonylphenol began 28 days
      prior to their mating at concentrations of 5 ppm, 100 ppm, and 500 ppm for
      genistein or 25 ppm, 200 ppm, and 750 ppm for p-nonylphenol. Exposure of the
      offspring continued throughout gestation and lactation, as well as in their chow
      after weaning, until they were sacrificed at 140 days of age for
      immunohistochemical labeling of the calbindin D28k-labeled subdivision of the
      SDN: the CALB-SDN. Both genistein and nonylphenol were found to increase the
      volume of the CALB-SDN in male rats (p's < 0.01), but not in female rats.

PMID- 15456916
TI  - Effect of genistein as a selective estrogen receptor beta agonist on the
      expression of Calbindin-D9k in the uterus of immature rats.
AB  - Genistein, a phytoestrogen possessing a high affinity for estrogen receptor beta
      (ERbeta), is of increasing interest because of its possible influence on the
      physiology of mammalian reproductive tracts. Although estrogen has been
      demonstrated to regulate Calbindin-D9k (CaBP-9k) in the rat uterus as with other
      calcium binding proteins, the role of ERbeta on the modulation of CaBP-9k remains
      to be elucidated. To elucidate the effect of genistein as a selective ERbeta
      agonist on uterine expression of CaBP-9k mRNA and protein, immature female rats
      were injected with genistein daily for three consecutive days in a dose-dependent
      (0.4, 4, and 40 mg/kg/day) and time-dependent (40 mg/kg/day; 3, 6, 12, 24, 48,
      and 72 h) manner. Then, the expression of CaBP-9k mRNA and protein was analyzed
      by Northern hybridization and Western blot, respectively, in the absence or
      presence of ICI 182,780 (ICI), an estrogen antagonist. In addition, the protein
      levels of ERalpha and ERbeta and mRNA level of progesterone receptor (PR) were
      further measured following genistein treatment to elucidate which of ERs is
      involved in CaBP-9k modulation. In a dose-dependent experiment, the highest dose
      of genistein (40 mg/kg/day) for 3 days significantly induced uterine CaBP-9k
      protein as 17beta-estradiol (E2) did. In addition, its maximal mRNA expression
      was observed at 3 and 6 h, and it returned to control level at 24 h in a time
      dependent experiment. In parallel with its mRNA level, the protein level of CaBP
      9k was significantly induced by genistein at 3 h and sustained up to 48 h. The
      pretreatment with ICI, followed by genistein or E2, completely blocked genistein-
      and E2-induced CaBP-9k protein in the uterus of immature rats. Interestingly,
      genistein was demonstrated to induce ERalpha protein, but not ERbeta and PR mRNA,
      an E2-responsive gene, in this tissue. These results imply that genistein, an
      ERbeta ligand, may regulate CaBP-9k gene through ERalpha pathway. Taken together,
      the present study demonstrated that genistein enhanced CaBP-9k gene via ERalpha
      in the uterus of immature rats, suggesting that ERalpha may be a key mediator in
      uterine CaBP-9k gene induction in immature rats.

PMID- 15456917
TI  - Endocrine disruption in adolescence: immunologic, hematologic, and bone effects
      in monkeys.
AB  - Environmental contaminants with estrogenic properties have the potential to alter
      pubertal development. In addition to the reproductive system, other systems that
      mature under the influence of estrogen could be affected. This study examined the
      effect on immune, hematologic, and bone mass parameters of treatment with
      estrogenic agents (methoxychlor, MXC, 25 and 50 mg/kg/day; diethylstilbestrol,
      DES, 0.5 mg/kg/day) given in the peripubertal period to female rhesus monkeys.
      DES had striking effects on several parameters assessed measures CBC and clinical
      chemistry including hematocrit, hemoglobin, serum albumin, liver transaminases,
      and lipids. Circulating lymphocytes, particularly B cells, were depressed by DES,
      and a maturational shift in a memory T-cell population was altered. Bone mass and
      length, as measured after a 9-month recovery period, were significantly lower in
      the DES group and bone mass tended to be reduced in the femur of the MXC50 group
      relative to controls. In conclusion, the data indicate that DES had a clear
      effect on immunohematology and bone growth, while MXC influenced fewer
      parameters. Disruption in these systems during puberty could alter adolescent
      risk for anemia and infectious disease and subsequent adult risk for diseases
      such as osteoporosis, heart disease, and autoimmune disease.

PMID- 15456918
TI  - Pharmacokinetics of dibutylphthalate in pregnant rats.
AB  - Dibutylphthalate (DBP) can cause adverse effects on the developing male
      reproductive tract when administered late in gestation to pregnant rats. The
      objectives of this study were to evaluate the metabolism of DBP in female rats,
      and the pharmacokinetics of DBP in pregnant rats on gestational day (g.d.) 20.
      The identities of DBP metabolites in urine and in maternal and fetal plasma were
      confirmed by LC-MS/MS, as monobutylphthalate (MBP) and its glucuronide,
      monohydroxybutylphthalate and its glucuronide, and butanoic acid phthalate and
      its glucuronide. An LC-MS/MS method was developed for the quantitation of MBP and
      its glucuronide. MBP and MBP glucuronide were quantitated in maternal and fetal
      plasma, and in amniotic fluid from pregnant rats administered a single dose of
      DBP (50, 100, or 250 mg/kg by gavage in corn oil) on g.d. 20. The
      pharmacokinetics of MBP and MBP glucuronide were determined. MBP was the major
      metabolite in maternal and fetal plasma. With increasing dose, there was a
      nonlinear increase in area under the curve (AUC) for MBP, with a ten-fold
      increase in maternal plasma, and an eight-fold increase in fetal plasma between
      50 mg/kg and 250 mg/kg. In amniotic fluid, the major metabolite initially was
      MBP, but by 24 h after dosing, the major metabolite was MBP glucuronide. Isomers
      of the MBP glucuronide were detected in amniotic fluid, suggesting acyl group
      migration, known to occur with acyl glucuronides. This study indicated that MBP,
      thought to be the active metabolite of DBP, can cross the placenta in late
      gestation, and that the metabolism of MBP is saturable.

PMID- 15456919
TI  - Human carcinogenic risk evaluation, Part V: The national toxicology program
      vision for assessing the human carcinogenic hazard of chemicals.
AB  - The National Toxicology Program (NTP) has over 25 years of experience in the
      design, performance, and interpretation of assays for identifying carcinogenic
      hazards to humans. Through the years we have examined alternative assays and
      adjunct assays to the standard rodent cancer bioassay including batteries of
      genetic toxicity tests and genetically modified mouse models. As our collective
      understanding of carcinogenesis advances, toxicologists and regulatory scientists
      will at some point begin to rely on mechanism-based biological observations
      rather than the two-year rodent bioassay to predict human cancer hazards. The
      goal of the NTP Vision for the 21st Century is to develop the science base that
      will advance the use of mechanism-based biological observations, eventually
      providing a replacement for disease-specific toxicology models in the protection
      of public health.

PMID- 15456920
TI  - A novel nonradioactive method for measuring aromatase activity using a human
      ovarian granulosa-like tumor cell line and an estrone ELISA.
AB  - Aromatase is a key enzyme in steroidogenesis and plays an important role in
      sexual differentiation, fertility, and carcinogenesis. Importantly, a variety of
      chemicals in the environment may influence its activity and thereby disrupt
      endocrine function. In the current studies, we developed a novel nonradioactive
      method for measuring aromatase activity that uses a specific ELISA for estrone
      along with KGN human ovary granulosa-like carcinoma cells. This cell line has
      relatively high aromatase activity, and because it lacks 17alpha-hydroxylase, it
      secretes little or no androstenedione, 17beta-estradiol, or estrone. Therefore,
      aromatase activity can be assayed simply by measuring the production of estrone
      in the culture medium after addition of the substrate, androstenedione.
      Furthermore, by making a slight change in the commercial ELISA kit and optimizing
      the experimental conditions, we developed a sensitive aromatase assay that could
      measure a wide range of estrone concentrations with very low interference by
      androgens. We used this assay to investigate the effects of 23 chemicals that
      have been previously reported to affect aromatase activity in vitro. We confirmed
      that 17 of 23 test chemicals had inhibitory or inducible effects, although the
      specific effects of some were different than previously reported. In conclusion,
      we have developed a simple, sensitive, and nonradioactive assay that can be used
      for large-scale screening of compounds that can disrupt endocrine function by
      influencing aromatase activity.

PMID- 15456921
TI  - Inhibition of matrix metalloproteinases minimizes hepatic microvascular injury in
      response to acetaminophen in mice.
AB  - The acetaminophen (APAP)-induced hepatic centrilobular necrosis is preceded by
      hepatic microcirculatory dysfunction including the infiltration of erythrocytes
      into the space of Disse. The purpose of this study was to examine the involvement
      of matrix metalloproteinases (MMPs) in the hepatic microvascular injury elicied
      by APAP. Male C57Bl/6 mice were pretreated with 2-[(4-biphenylsulfonyl) amino]-3
      phenyl-propionic acid, an MMP-2/MMP-9 inhibitor (5 mg/kg, ip) 30 min before oral
      gavage with 600 mg/kg of APAP. The hepatic microvasculature in anesthetized mice
      was observed using established in vivo microscopic methods 2 and 6 h after APAP.
      The levels of mRNAs and activities of MMP-2 and MMP-9 in the liver were increased
      from 1 h through 6 h after APAP gavage. APAP increased alanine transferase (ALT)
      levels (41.1-fold) and resulted in centrilobular hemorrhagic necrosis at 6 h.
      Pretreatment with 2-[(4-biphenylsulfonyl) amino]-3-phenyl-propionic acid
      attenuated ALT values by 71% as well as the necrosis. APAP decreased the numbers
      of perfused sinusoids in centrilobular regions by 30% and increased the area
      occupied by infiltrated erythrocytes into Disse space. 2-[(4-Biphenylsulfonyl)
      amino]-3-phenyl-propionic acid restored the sinusoidal perfusion to 90% of
      control levels and minimized extrasinusoidal area occupied by erythrocytes. The
      present study showed that increased MMPs during APAP intoxication are associated
      with hepatocellular damage and with hepatic microcirculatory dysfunction
      including impaired sinusoidal perfusion and infiltration of erythrocytes in Disse
      space. 2-[(4-Biphenylsulfonyl) amino]-3-phenyl-propionic acid attenuated APAP
      induced parenchymal and microvascular injury. These results suggest that MMPs
      participate in APAP hepatotoxicity mediated by sinusoidal endothelial cell
      injury, which results in impairment of microcirculation.

PMID- 15456922
TI  - Spatial alternation deficits following developmental exposure to Aroclor 1254
      and/or methylmercury in rats.
AB  - Polychlorinated biphenyls (PCBs) and methylmercury (MeHg) are ubiquitous
      environmental contaminants that alter cognitive function in both humans and
      animals. Because PCBs and MeHg often occur together in the environment, it is
      important to understand whether these two contaminants have the potential to
      interact, causing additive or greater than additive effects. The current study
      examined the combined effects of gestational and lactational exposure to Aroclor
      1254 (A1254), a commercial PCB mixture, and MeHg on a series of spatial
      alternation tasks including cued spatial alternation (CA), non-cued spatial
      alternation (NCA), and delayed spatial alternation (DSA) in rats using standard
      two-lever operant testing chambers. Pregnant Long-Evans rats received either 6
      mg/kg A1254 pipetted onto a Keebler Vanilla Wafer cookie (PCB-only group), 0.5
      ppm. MeHg dissolved in the drinking water (MeHg-only group), 6 mg/kg A1254 + 0.5
      ppm. MeHg (PCB + MeHg group), or corn oil vehicle and normal tap water (control
      group) beginning 28 days prior to mating and continuing through postnatal day 16.
      One male and one female from each litter began testing on spatial alternation at
      approximately 110 days of age. Animals were reinforced for pressing the lever
      opposite that pressed on the previous trial. In general, animals exposed to A1254
      and/or MeHg were impaired relative to control rats on the NCA and DSA tasks.
      Significant reductions in NCA performance were observed in the MeHg-only and PCB
      + MeHg groups, while significant reductions in DSA performance were observed in
      the PCB-only and MeHg-only groups. The PCB + MeHg group showed a similar
      magnitude reduction in performance on DSA, but this difference was not
      statistically significant due to increased variability in that group. The
      reductions in DSA performance were observed across most of the delays, indicating
      that memory impairments were not likely the cause of the deficit. Instead, the
      DSA deficits following exposure to A1254 and/or MeHg are indicative of either an
      associative or attentional impairment. The results from the current study
      indicate that combined exposure to PCBs and MeHg does not exacerbate the PCB- or
      MeHg-induced impairments on spatial alternation tasks.

PMID- 15456923
TI  - Recovery from welding-fume-exposure-induced lung fibrosis and pulmonary function
      changes in sprague dawley rats.
AB  - Welder's pneumoconiosis has generally been determined as benign based on the
      absence of pulmonary function abnormalities in welders with marked radiographic
      abnormalities. Yet, there have also been several reports on welders with
      respiratory symptoms, indicating lung function impairment, X-ray abnormalities,
      and extensive fibrosis. Accordingly, this study attempted to investigate the
      inflammatory responses and pulmonary function changes in rats during a 60-day
      welding-fume-inhalation exposure period to elucidate the process of fibrosis. The
      rats were exposed to manual metal-arc stainless-steel welding fumes (MMA-SS) with
      total suspended particulate concentrations of 64.8 +/- 0.9 (low dose) and 107.8
      +/- 2.6 mg/m3 (high dose) for 2 h per day in an inhalation chamber for 60 days.
      Animals were sacrificed after the initial 2-h exposure and after 15, 30, and 60
      days, and the pulmonary function was also measured every week after the daily
      exposure. Elevated cellular differential counts were also measured in the
      acellular bronchoalveolar lavage fluid of the rats exposed to the MMA-SS fumes
      for 60 days. Among the pulmonary function test parameters, only the tidal volume
      showed a statistically significant and dose-dependent decrease after 35 to 60
      days of MMA-SS welding-fume exposure. When the rats exposed to the welding fumes
      were left for 60 days to recover their lung function and cellular
      differentiation, recovery was observed in both the high and low-dose rats exposed
      up to 30 days, resulting in the disappearance of inflammatory cells and
      restoration of the tidal volume. The rats exposed for 60 days at the low dose
      also recovered from the inflammation and tidal volume loss, yet the rats exposed
      for 60 days at the high dose did not fully recover even after a 60-day recovery
      period. Therefore, when taken together, the results of the current study suggest
      that a decrease in the tidal volume could be used as an early indicator of
      pulmonary fibrosis induced by welding-fume exposure in Sprague Dawley rats, and
      fibrosis would seem to be preventable if the exposure is short-term and moderate.

PMID- 15456924
TI  - Role of oxidant stress in lawsone-induced hemolytic anemia.
AB  - Lawsone (2-hydroxy-1,4-naphthoquinone) is the active ingredient of henna
      (Lawsonia alba), the crushed leaves of which are used as a cosmetic dye.
      Application of henna can induce a severe hemolytic anemia, and lawsone is thought
      to be the causative agent. Administration of lawsone to rats has been shown to
      induce a hemolytic response that is associated with oxidative damage to
      erythrocytes. However, direct exposure of isolated erythrocytes to lawsone did
      not provoke oxidative damage, suggesting that lawsone must undergo extra
      erythrocytic bioactivation in vivo. In the present study, the survival of rat
      51Cr-labeled erythrocytes in vivo after in vitro exposure to lawsone and its
      hydroquinone form, 1,2,4-trihydroxynaphthalene (THN) has been examined. Neither
      lawsone nor THN were directly hemolytic or methemoglobinemic, even at high
      concentrations (>3 mM). Lawsone had no effect on erythrocytic GSH levels, whereas
      THN (3 mM) induced a modest depletion (approximately 30%). Cyclic voltammetry
      revealed that the lack of hemotoxicity of lawsone was associated with a poor
      capacity to undergo redox cycling. In contrast, ortho-substituted 1,4
      naphthoquinones without a 2-hydroxy group, such as 2-methyl- and 2-methoxy-1,4
      naphthoquinone, were redox active, were able to deplete GSH, and were direct
      acting hemolytic agents. An oxidant stress-associated hemolytic response to
      lawsone could be provoked, however, if it was incubated with GSH-depleted
      erythrocytes. The data suggest that lawsone is a weak direct-acting hemolytic
      agent that does not require extra-erythrocytic metabolism to cause hemotoxicity.
      Thus, the hemolytic response to henna may be restricted to individuals with
      compromised antioxidant defenses.

PMID- 15456925
TI  - The capacity of particles to increase allergic sensitization is predicted by
      particle number and surface area, not by particle mass.
AB  - Particle exposure has traditionally been monitored as mass concentration of PM10
      (particles with an aerodynamic diameter less than 10 microm), more recently also
      as PM2.5. The mass concentration is strongly influenced by the large particles.
      Therefore, particle mass is a poor measure for characterizing the amount of the
      small, possibly more biologically potent particles. We used polystyrene particles
      (PSP) ranging in diameter from 0.0588 to 11.14 microm, carbon black (CB), and
      diesel exhaust particles (DEP), to study the adjuvant effect of particles on the
      immune response to the allergen ovalbumin (OVA) after sc injection into the
      footpad of BALB/cA mice. At a given mass dose, the small particles (0.0588 and
      0.202 microm PSP, CB, and DEP) increased the allergen-specific IgE serum levels
      to a substantially higher degree than the larger particles (1.053, 4.64, and
      11.14 microm PSP). Further, in the draining lymph node during the primary
      response, the fine particles (0.202 microm) with OVA increased cell numbers,
      expression of surface markers (CD19, MHC class II, CD86, and CD23) and ex vivo
      production of IL-4 and IL-10, whereas the largest (11.14 microm) particles did
      not. Linear regression analyses indicated that the IgE response was not predicted
      by particle mass (R2 = 0.06), but was predicted by the total particle surface
      area (R2 = 0.64), number of particles (R2 = 0.62), and particle diameter (R2 =
      0.58). In conclusion, we found that fine particles exerted stronger adjuvant
      effects on allergic responses than larger particles at equal mass doses.
      Consequently, the dose described as total particle surface area or particle
      number predicts the adjuvant effect of particles better than the currently used
      particle mass.

PMID- 15456926
TI  - Enhanced acetaminophen toxicity by activation of the pregnane X receptor.
AB  - The pregnane X receptor (PXR) is a ligand-activated transcription factor and
      member of the nuclear receptor superfamily. Activation of PXR represents an
      important mechanism for the induction of cytochrome P450 3A (CYP3A) enzymes that
      can convert acetaminophen (APAP) to its toxic intermediate metabolite, N-acetyl-p
      benzoquinone imine (NAPQI). Therefore, it was hypothesized that activation of PXR
      plays a major role in APAP-induced hepatotoxicity. Pretreatment with the PXR
      activator, pregnenolone 16alpha-carbonitrile (PCN), markedly enhanced APAP
      induced hepatic injury, as revealed by increased serum ALT levels and hepatic
      centrilobular necrosis, in wild-type but not in PXR-null mice. Further analysis
      showed that following PCN treatment, PXR-null mice had lower CYP3A11 expression,
      decreased NAPQI formation, and increased maintenance of hepatic glutathione
      content compared to wild-type mice. Thus, these results suggest that PXR plays a
      critical role in APAP-induced hepatic toxicity, probably by inducing CYP3A11
      expression and hence increasing bioactivation.

PMID- 15456927
TI  - Organ slice viability extended for pathway characterization: an in vitro model to
      investigate fibrosis.
AB  - Liver slice viability is extended to 96 h for rat, expanding the use of this in
      vitro model for studying mechanisms of injury and repair, including pathways of
      fibrosis. The contributing factors to increased organ slice survival consist of
      the use of a preservation solution for liver perfusion and slice preparation,
      obtaining rats that are within the weight range of 250-325 g, placing a cellulose
      filter atop the titanium mesh roller-insert to support the slice, and maintaining
      the slices in an optimized culture medium which is replaced daily. The liver
      slices remain metabolically active, synthesizing adenosine triphosphate (ATP),
      glutathione, and glycogen, and exhibit preserved organelle integrity and slice
      morphology. Slice preparation results in 2-cut surfaces which likely triggers a
      repair and regenerative response. The fibrogenic pathways are evident by the
      activation of stellate cells, the proliferation of myofibroblast-like cells, and
      an increased collagen deposition by 48 h. Markers indicative of activated
      stellate cells, alpha-smooth muscle actin, collagen 1a1, desmin, and HSP47 are
      substantiated by real time-PCR. Increased staining of alpha-smooth muscle actin
      initially around the vessels and by 72-96 h in the tissue is accompanied by
      increased collagen staining. Microarray gene expression revealed extracellular
      matrix changes with the up-regulation of cytoskeleton, filaments, collagens, and
      actin genes; and the down-regulation of genes linked with lipid metabolism. The
      improvements in extending liver slice survival, in conjunction with its three
      dimensional multi-cellular complexity, increases the application of this in vitro
      model for investigating pathways of injury and repair, and fibrosis.

PMID- 15456928
TI  - Effects of polybrominated diphenyl ethers on basal and TCDD-induced
      ethoxyresorufin activity and cytochrome P450-1A1 expression in MCF-7, HepG2, and
      H4IIE cells.
AB  - Polybrominated diphenylethers (PBDEs) are used as additive flame-retardants in
      consumer products to reduce the chances of ignition and burning. Levels of
      certain PBDE congeners have been increasing in fish, wildlife, and human tissues
      during the last decades. Some PBDEs are lipophilic and persistent, resulting in
      bioaccumulation in the environment. The structural similarity of PBDEs to other
      polyhalogenated aromatic hydrocarbons such as PCBs, has raised concerns that
      PBDEs might act as agonists for the aryl hydrocarbon receptor (AhR). To study the
      possible AhR-mediated effects of the environmentally relevant PBDEs (BDE47, 77,
      99, 100, 153, 154, 183, 209), the induction of cytochrome P450-1A1 (CYP1A1) was
      studied in human breast carcinoma (MCF-7), human hepatocellular carcinoma
      (HepG2), and rat hepatoma (H4IIE) cells. 7-Ethoxyresorufin-O-deethylase (EROD)
      was used as a marker for CYP1A1 activity. Cells were exposed for 72 h to various
      PBDE concentrations (0.01-10 microM). Positive controls were 2,3,7,8-TCDD (0.001
      2.5 nM) and PCB126 (0.01-10 nM). None of these PBDEs was capable of inducing EROD
      activity; this was confirmed by real time RT-PCR for CYP1A1 mRNA. However, in
      cells exposed to PBDEs in combination with TCDD, a concentration-dependent
      decrease in TCDD-induced EROD activity occurred. Co-exposure of BDE153 (10 muM)
      and a maximally inducing concentration of TCDD (1 nM) reduced EROD activity to
      49% of the maximum induction by TCDD alone. All tested PBDEs showed similar
      effects in each cell line, though quantitative differences were observed. The
      observed decrease in CYP1A1 activity was not due to PBDE-dependent catalytic
      inhibition of EROD activity or cytotoxicity, nor were decreased CYP1A1 mRNA
      levels observed. However, inhibition of luciferase induction in mouse (Hepa) and
      rat (H4IIE) hepatoma cells containing a stably transfected AhR-responsive
      luciferase reporter gene, suggests that BDE77 is a weak AhR antagonist or partial
      agonist.

PMID- 15456929
TI  - Gene expression changes in the immature rat uterus: effects of uterotrophic and
      sub-uterotrophic doses of bisphenol A.
AB  - J. C. Gould et al., 1998, Mol. Cell Endocrinol. 142, 203-214, have reported that
      administration of 5-150 mg/kg/day BPA to immature rats leads to increases in
      uterine peroxidase activity and progesterone receptor (PR) protein levels in the
      absence of a uterotrophic response. These observations are of interest given
      current concerns regarding the adequacy of the uterotrophic assay to act as a
      sentinel for the estrogenic activity of chemicals in vivo. Therefore, the
      uterotrophic activity of BPA to the immature rat has been re-evaluated over the
      dose range 2 microg/kg-800 mg/kg/day. Expression levels of three estrogen
      responsive uterine genes were determined using real-time RT-PCR--namely,
      complement component 3, lipocalin 2, and PR. 18S rRNA and RNA polymerase II large
      subunit acted as control genes. Observations of gene expression were made 4 h and
      72 h after the first of three daily po administrations of BPA. Increases in gene
      expression were observed over the uterotrophic dose range (approximately 200-800
      mg/kg BPA). Over the dose range 2 microg/kg-20 mg/kg BPA there was no
      uterotrophic response and no increase in gene expression. We conclude that BPA
      does not produce reproducible changes in gene expression in the uterus of
      immature rats at dose levels that are not also uterotrophic. Therefore, in the
      present study, the no effect level for uterotrophic activity for BPA coincided
      with the no transcriptional effect level for uterine genes.

PMID- 15456930
TI  - Biochemical identification of the dopamine D2 receptor domains interacting with
      the adenosine A2A receptor.
AB  - Functional interactions between adenosine A2A and dopamine D2 receptors have been
      demonstrated both at the D2 agonist-binding and second messenger levels. The
      present studies use a [3H]dopamine-binding assay as a sensitive measure of A2A
      receptor-mediated modulation of D2 receptors. Co-incubation with an A2A receptor
      agonist increased the Kd value of high-affinity [3H]dopamine-binding sites of the
      D2 receptor without changing their Bmax values in a cotransfected cell line. This
      interaction was shown to be subtype specific, as the A2A receptor agonist did not
      modulate the affinity of the D1 receptor for [3H]dopamine. The domains of the D2
      receptor important for the A2A/D2 receptor interaction were studied with chimeric
      dopamine D2/D1 receptors. The results showed that the A2A receptor agonist still
      strongly reduced the affinity of a D2/D1 chimera with the sixth transmembrane
      (TM) domain and third extracellular loop from the D1 receptor. However, the A2A
      receptor agonist was not able to modulate a D2/D1 chimeric receptor containing
      the fifth and sixth TM domains and the third intracellular and extracellular
      loops from the D1 receptor, indicating that the fifth TM domain and/or the third
      intracellular loop may be involved in the interaction between A2A and D2
      receptors.

PMID- 15456931
TI  - Brain injury-dependent expression of activity-dependent neuroprotective protein.
AB  - Activity-dependent neuroprotective protein (ADNP), a crucial brain development
      factor, contains a unique sequence, termed NAPVSIPQ, which protects mice against
      closed head injury (CHI). The aim of this study was to determine whether CHI
      affects ADNP mRNA expression in the injured brain hemisphere. Male C57JBL/6J mice
      were subjected to CHI. Brains were removed 5 h, 24 h, 7 d, and 29 d post-CHI. A
      comparison was made between ADNP mRNA in the injured versus the noninjured
      hemisphere using real-time polymerase chain reaction. A nonsignificant change (p
      >0.05) was found 5 h, 24 h, and 7 d post-CHI. However, a significant increase (p
      <0.05) in ADNP mRNA expression was detected in the injured cerebral hemisphere 29
      d post-CHI. The data presented may be associated with ADNP's crucial involvement
      in brain development and response to injury.

PMID- 15456932
TI  - A neuroprotective peptide antagonizes fetal alcohol exposure-compromised brain
      growth.
AB  - We evaluated a 9-amino-acid peptide, SALLRSIPA (SAL), an agonist of activity
      dependent neurotrophic factor (ADNF), for its protective properties against fetal
      alcohol-related brain growth retardation, using an established liquid diet model
      of alcohol-related neurodevelopmental disorder (ARND) in C57BL/6 mice. Alcohol
      exposure during neurulation reduced body weight, head size, and specifically
      brain weight and volume. Major gross brain deficits include underdevelopment of
      brain areas, cortical thinning, ventricle enlargement, and restricted midline
      neural tissue growth leading to openings at the roof/floor plate. SALLRSIPA (SAL)
      treatment increased fetal body weight and restored brain weight, brain volume,
      and regional brain size. Furthermore, SAL restored cortical thickness, reduced
      the size and frequency of neural tube openings, and attenuated ventricular
      enlargement. The ability of SAL to antagonize alcohol-retarded brain growth and
      development of forebrain and midline neural tube at midgestation suggests its
      potential use as an antagonist against fetal alcohol- rendered microencephaly
      early in development.

PMID- 15456933
TI  - Caffeine induces sonic hedgehog gene expression in cultured astrocytes and
      neurons.
AB  - Caffeine affects early in vivo murine brain development by accelerating the
      evagination of the primitive neuroepithelium into telencephalic vesicles. In this
      model, caffeine induces the expression of the regulatory subunit alpha of protein
      kinase A (PKA RI alpha) and of Sonic hedgehog (Shh). The understanding of the
      molecular mechanisms linking caffeine and neural gene expression would benefit
      from a reproducible in vitro model. Accordingly, the present study aimed to
      determine whether caffeine modulated the expression of these genes in primary
      neuronal and astroglial cultures derived from developing murine neocortex. Using
      real-time PCR, the results showed that caffeine induced robust overexpression of
      Shh mRNA in both cell types without significantly modifying PKA RI alpha gene
      expression.

PMID- 15456934
TI  - MAP kinase activation by fluoxetine and its relation to gene expression in
      cultured rat astrocytes.
AB  - Chronic treatments with antidepressants active on major depressive disorders
      influence pathways involved in cell survival and plasticity. As astrocytes seem
      to play a key role in the protection of brain cells, we investigated in these
      cells the rapid effects of the antidepressant fluoxetine (Prozac) on signaling
      cascades and gene induction, which probably play a role in neuroprotection. We
      show here that fluoxetine alone activates the extracellular signal-regulated
      protein kinase (Erk) and p38 mitogen-associated protein (MAP) kinase cascades. RT
      PCR revealed that genes, modulated in brain by long-term fluoxetine treatment,
      are rapidly induced by fluoxetine in cultured astrocytes: brain-derived nerve
      factor (BDNF) and its receptors, glial-derived nerve factor (GDNF) and deiodinase
      3 (D3). Induction of D3 by fluoxetine is inhibited by U0126 and SB203580,
      suggesting that Erk and p38 MAP kinases are involved. Glial-derived nerve factor
      (GDNF) induction by fluoxetine is prevented by U0126, suggesting that Erk is
      implicated. Brain-derived nerve factor (BDNF) induction seems mediated by other
      signaling pathways. In conclusion, we show that fluoxetine alone rapidly
      activates mitogen activated protein (MAP) kinase cascades in rat astrocytes and
      that genes involved in neuroprotection are induced in a few hours in a MAP kinase
      dependent or -independent manner.

PMID- 15456935
TI  - SRC-1 is involved in the control of the gene expression of myelin protein Po.
AB  - Steroid receptor coactivator-1 (SRC-1) has a crucial role in many different
      biological effects mediated by nuclear receptors. However, in spite of its
      ubiquitous expression, there are no data regarding its possible involvement in
      nuclear receptor transcriptional activity at the level of the peripheral nervous
      system. We investigated whether this coactivator might have a role in the control
      of glycoprotein Po gene expression. This myelin protein is a specific product of
      Schwann cells, with a fundamental role in the maintenance and functionality of
      peripheral myelin. Po is known to be stimulated by progesterone and by its 5alpha
      reduced metabolite, dihydroprogesterone (DHP), through the corresponding steroid
      receptor. To determine whether the effect exerted by DHP on Po mRNA levels could
      be affected by and therefore associated with altered levels of SRC-1, a mouse
      Schwann cell line was stably transfected to over- or underexpress this
      coactivator. We found that SRC-1 overexpressing cells are more responsive to Po
      mRNA induction by DHP, whereas the effect of the steroid is completely lost in
      SRC-1-deficient cells. Interestingly, SRC-1 levels are also positively correlated
      with Po gene expression independently of DHP exposure. Finally, DHP treatment
      increases not only Po but also SRC-1 mRNA levels. Altogether, these data indicate
      for the first time that in rat Schwann cells, SRC-1 plays a role in the
      regulation of one of the most typical proteins of peripheral myelin.

PMID- 15456936
TI  - Regional energy metabolism following short-term neural stem cell transplantation
      into the injured spinal cord.
AB  - Stem cells have been shown to partly restore central nervous system (CNS)
      function after transplantation into the injured CNS. However, little is known
      about their influence on acute energy metabolism after spinal cord injury. The
      present study was designed to analyze regional changes in energy metabolites.
      Young adult mice were subjected to laminectomy with subsequent hemisection at the
      L2/3 vertebral level. Immediately thereafter a stable clone of murine neural stem
      cells (NSCs) was injected into the lesion site. After 4 and 24 h, spinal cords
      were removed and ATP, glucose, and lactate were analyzed by a bioluminescence
      approach in serial sections and compared to a laminectomized (intact control),
      hemisected-only or hemisected vehicle-injected control group. At both time
      points, ATP content of the hemisected group in the tissue segments adjacent to
      the lesion was increased when compared to the laminectomized control. At the
      lesion site ATP content decreased significantly at 24 h in the cell-transplanted
      group when compared to the laminectomized control group. Glucose content
      decreased at the lesion site and in segments adjacent to the lesion at both time
      points and in all experimental groups when compared to the laminectomized control
      group. Lactate content decreased significantly at 4 h in the caudal segments of
      the vehicle-injected group and in both adjacent segments of the transplanted
      group when compared to the laminectomized control. At the lesion site, lactate
      content decreased significantly at 4 and 24 h in the cell-transplanted group,
      when compared to the laminectomized control. The area of ATP decline at the
      lesion site 24 h postinjury was significantly lower in the vehicle control group
      as compared to the hemisected or transplanted group. The decrease in glucose
      combined with an increase in ATP in the lesion-adjacent segments may indicate
      that the tissue responds with an increased use of glucose to support itself with
      sufficient ATP. The significant decrease in glucose, lactate, and ATP in the cell
      transplanted group at 24 h may indicate a high metabolic need of the stem cells.
      The lower area of ATP decline 24 h after vehicle administration suggests that the
      vehicle solution washes out toxic mediators, thus ameliorating hemisection
      dependent secondary tissue damage.

PMID- 15456937
TI  - Lithium-mediated phosphorylation of glycogen synthase kinase-3beta involves PI3
      kinase-dependent activation of protein kinase C-alpha.
AB  - Lithium, a known mood-stabilizer frequently used in treatment of bipolar
      disorders, is an effective glycogen synthase kinase-3beta (GSK-3beta) inhibitor.
      This led to the idea that GSK-3beta is an in vivo target directly inhibited by
      lithium. As lithium is a weak in vitro inhibitor of GSK-3beta (IC50=2 mM),
      however, we speculated that it inhibits GSK-3beta via an indirect, yet unknown,
      mechanism. The present studies show that lithium increased the phosphorylation of
      a key inhibitory site of GSK-3beta, serine-9 (Ser-9), in HEK293 cells and in PC12
      cells. This phosphorylation was significantly reduced by protein kinase C (PKC)
      inhibitors GF109203X and Ro31-8425, as well as GO6976, an effective inhibitor
      toward conventional PKC isoforms (cPKC). Consistent with these results, lithium
      increased PKC-alpha activity approximately twofold in both cell lines. Because
      PI3 kinase is a potential upstream regulator of cPKC, its inhibition by
      wortmannin or LY294002 also abolished the lithium-induced serine phosphorylation
      of GSK-3beta in HEK293 and PC12 cells. Moreover, lithium did not activate PKB,
      and in addition, its activity was not dependent on the presence of medium
      inositol nor did it affect the autophosphorylation activity of GSK-3beta.
      Finally, intracerebroventricular injection of lithium increased GSK-3beta Ser-9
      phosphorylation and enhanced PKC-alpha activity 1.8-fold in mouse hippocampus,
      confirming this lithium response in vivo. Our studies propose a new mechanism by
      which lithium indirectly inhibits GSK-3beta via phosphatidylinositol 3 kinase-
      dependent activation of PKC-alpha.

PMID- 15456938
TI  - A novel imaging probe for in vivo detection of neuritic and diffuse amyloid
      plaques in the brain.
AB  - Extensive deposition of neuritic and diffuse amyloid plaques in the brain is a
      critical event for the pathogenesis of Alzheimer's disease (AD) and considered to
      start before the appearance of clinical symptoms. In vivo detection of these
      brain beta-amyloid (Abeta) deposits using positron emission tomography (PET),
      therefore, would be a useful marker for presymptomatic detection of AD. To
      develop a new agent for PET probe of imaging neuritic and diffuse amyloid
      deposits, novel fluorescent compounds, including styryl-fluorobenzoxazole
      derivatives, were examined. These compounds showed a high binding affinity for
      both synthetic Abeta1-40 and Abeta1-42 aggregates. Some of these compounds also
      displayed distinct staining of neuritic and diffuse amyloid plaques in AD brain
      sections. A biodistribution study of styryl-fluorobenzoxazole derivatives in
      normal mice exhibited excellent brain uptakes (4.5-5.5% injected dose/g at 2 min
      postinjection). Furthermore, iv administration of BF-145, a styryl
      fluorobenzoxazole derivative, demonstrated specific in vivo labeling of compact
      and diffuse amyloid deposits in an APP23 transgenic mouse brain, in contrast to
      no accumulation in a wild-type mouse brain. These findings suggest that BF-145 is
      a potential candidate as a probe for imaging early brain pathology in AD
      patients.

PMID- 15456939
TI  - Modified single-stranded oligonucleotides inhibit aggregate formation and
      toxicity induced by expanded polyglutamine.
AB  - Huntington's disease (HD) is caused by an increase in the length of the poly(Q)
      tract in the huntingtin (Htt) protein, which changes its solubility and induces
      aggregation. Aggregation occurs in two general phases, nucleation and elongation,
      and agents designed to block either phase are being considered as potential
      therapeutics. We demonstrate that inclusion formation can be retarded by
      introducing modified, single-stranded oligonucleotides into a model neuronal cell
      line. This cell-based assay is used in conjunction with a standardized
      biochemical assay to identify molecules that can disrupt the process of aggregate
      formation. Active oligonucleotides include a 6-mer containing a single
      phosphorothioate linkage on each terminus, a 53-mer and a 9-mer containing three
      phosphorothioate linkages at each end, and a 25-mer consisting of all modified
      RNA residues. The disruption process directed by the active oligonucleotides
      appears to be independent of sequence specificity and complementarity. In
      contrast, the activity is more dependent on the type of chemical modifications
      contained within the oligonucleotide. Some oligonucleotides that demonstrated
      inhibition activity were also found to extend the life span of PC12 cells after
      the toxic Htt aggregation process was induced. Our data provide the first
      evidence that short synthetic oligonucleotides inhibit a fundamental pathological
      pathway of HD and may provide the basis for a novel therapeutic approach.

PMID- 15456940
TI  - The splicing regulatory protein p18SRP is down-regulated in Alzheimer's disease
      brain.
AB  - Alzheimer's disease (AD) is the most common neurodegenerative disorder of aging,
      accounting for an estimated two-thirds of all cases of senile dementia. Using
      bioinformatics, the yeast two-hybrid-system, reverse transcription polymerase
      chain reaction, and fluorescence microscopy analysis, we demonstrate here that
      the new putative splicing regulatory protein p18SRP is a lysine-rich zinc finger
      domain-containing protein that interacts with the serine-arginine (SR)-rich
      splicing regulatory protein SRrp86. The additional finding of its down-regulation
      in the brain of AD subjects points to a possible pivotal role of p18SRP in the
      control of cellular survival.

PMID- 15456941
TI  - Caprine mucopolysaccharidosis IIID: fetal and neonatal brain and liver
      glycosaminoglycan and morphological perturbations.
AB  - Mucopolysaccharidosis IIID (MPS IIID) is a lysosomal storage disease associated
      with deficient activity of the enzyme N-acetylglucosamine 6-sulfatase (EC
      3.1.6.14), a lysosomal hydrolase in the heparan sulfate glycosaminoglycan (HS
      GAG) degradation pathway. In caprine MPS IIID, enzyme replacement therapy
      reversed early postnatal systemic but not primary or secondary central nervous
      system (CNS) substrate accumulations. The caprine MPS IIID large animal model
      system was used in this investigation to define the developmental profile of
      morphological and biochemical perturbations to estimate a time frame for
      therapeutic intervention. Light and electron microscopy were used to compare the
      CNS, liver, and kidney of normal +/+, MPS IIID carrier +/-, and MPS IIID-affected
      -/- goat kids (kids), at 60, 113-114, 128-129, and 135 d gestation (dg) of a 150
      d gestational period, at birth, and at 59-64 d of postnatal (d-pn) age. In the
      CNS of -/- kids, morphological correlations of HS-GAG and glycolipid
      accumulations were evident in early differentiating neurons at 60 dg. CNS and
      systemic developmental, regional, and cellular differences in -/- kids at all
      time points included more prominent and earlier accumulation of lucent, putative
      HS-GAG substrates in lysosomes of meningeal and perivascular macrophages and
      hepatic sinusoidal cells than in CNS, hepatic, or renal parenchymal cells. The
      amounts and compositions of HS-GAG substrates in the brain and liver of +/+, +/-,
      and -/- kids were determined at 60, 65, 113-114, and 128-135 dg, at birth, and 53
      78 d-pn. In the CNS of -/- kids, HS-GAG concentrations were variable and exceeded
      those of age-matched control tissue samples in the third but not the second
      trimester. In contrast, hepatic HS-GAG levels in -/- kids exceeded control values
      at all time points evaluated and paralleled the progressive morphological
      alterations. CNS and hepatic HS-GAG compositions in -/- kids were similar to each
      other and were more complex at all pre- and postnatal ages than those from
      control kids. Based on the time frame of development of CNS lesions and
      biochemical perturbations, prenatal therapeutic intervention in caprine MPS IIID
      is likely to be necessary to prevent or ameliorate substantive CNS and systemic
      lesions.

PMID- 15456942
TI  - Serum interleukin-6 soluble receptor in relation to interleukin-6 in stroke
      patients.
AB  - Cerebral ischemia triggers interleukin-6 (IL-6) release into blood. IL-6 is a key
      mediator of acute phase reaction. Markers of acute phase reaction (C-reactive
      protein, fibrinogen, fever) have been linked to poor prognosis in stroke
      patients. Interleukin-6 soluble receptor (sIL-6R) can potentiate IL-6 pro
      inflammatory activity. The aim of this study was to investigate the relationship
      between IL-6 and sIL-6R in stroke patients. Serum cytokine levels were measured
      in 18 stroke patients and 13 controls using the ELISA method. On the second day
      of stroke, IL-6 levels were significantly higher in stroke patients than in
      controls; sIL-6R levels did not differ significantly between groups. Three months
      after stroke, IL-6 levels did not differ significantly between groups; sIL-6R
      levels were significantly decreased in stroke patients when compared with that in
      controls and with levels in acute phase of stroke. Decreased sIL-6R early after
      stroke might reflect a regulatory mechanism attenuating inflammatory response.

PMID- 15456943
TI  - Inhibition of caspase-3 activation and apoptosis is involved in 3-nitropropionic
      acid-induced ischemic tolerance to transient focal cerebral ischemia in rats.
AB  - Our aim was to investigate the involvement of caspase-3 activation and apoptotic
      cell death in mitochondrial toxin 3-nitropropionic acid (3-NPA)-induced ischemic
      tolerance to transient focal cerebral ischemia in rats. Rats were administrated
      either vehicle control or 3-NPA ip doses of 20 mg/kg. Three days later, rats were
      exposed to 2 h of middle cerebral artery occlusion, followed by 24 h of
      reperfusion. Infarct volumes were assessed by 2,3,5-triphenyltetrazolium chloride
      (TTC) staining 24 h after reperfusion. We measured neural cell apoptosis in the
      cerebral ischemic penumbra by terminal deoxynucleotidyl transferase-mediated dUTP
      biotin in situ nick end labeling (TUNEL) and flow cytometry (FCM). Cleavage of
      the fluorogenic substrate zDEVD-afc was used to assay caspase-3 activity.
      Compared with the vehicle-injected group, pretreatment with 3-NPA reduced the
      infarct volume by 22.3% and decreased the number of TUNEL-positive neural cells
      and apoptotic percentages by 47% (p <0.05) and 43.9% (p <0.01), respectively. In
      terms of caspase-3 activity in ischemic penumbral tissues, the 3-NPA-pretreated
      group showed 13.9% (p <0.05) less caspase-3 activity than the control group. The
      development of 3-NPA-induced ischemic tolerance in brain may be related to
      decreases in caspase-3 activation, which leads to decreased neural cell
      apoptosis.

PMID- 15456944
TI  - Differential time course of effects of kappa-opioid agonist treatment on
      dynorphin A levels and kappa-opioid receptor density.
AB  - The effects of kappa-opioid agonist treatment on kappa-opioid receptor density
      and on dynorphin A levels in the rat brain were studied. Rats were treated with
      the selective kappa-opioid agonist U-69593 or vehicle for 5 d. Dynorphin A levels
      and kappa-opioid receptor binding were measured on day 8 (3 d after the last
      injection) or 22 (17 d after the last injection). On day 8, kappa-opioid receptor
      density was increased in the hypothalamus of rats treated with U-69593; there
      were no changes in the frontal cortex or caudate putamen. In contrast, there was
      an increase in dynorphin A levels in the frontal cortex and no changes in
      hypothalamus and caudate putamen in response to U-69593. On day 22, Bmax was
      decreased in frontal cortex and caudate putamen of U-69593-treated rats, whereas
      dynorphin A levels were increased in the caudate putamen and in the frontal
      cortex. These findings suggest that kappa-opioid receptor agonist treatment has
      long-term, continually changing effects on the kappa-opioid system.

PMID- 15456945
TI  - Mitochondrial enzymes in schizophrenia.
AB  - The responses of brain metabolism and blood flow to stimulation are diminished in
      the dorsolateral prefrontal cortexes (DLPFCs) of schizophrenic patients.
      Reductions in mitochondrial enzymes underlie diminished metabolism in several
      neurodegenerative diseases. Thus, we tested whether reductions in selected
      mitochondrial enzymes could underlie the changes in schizophrenia. The activities
      of the pyruvate dehydrogenase complex (PDHC), aconitase, isocitrate dehydrogenase
      (ICDH), and the alpha-ketoglutarate dehydrogenase complex (KGDHC) were determined
      on DLPFCs from patients with schizophrenia (n=26) and normal nonpsychiatric
      disease controls (n=13). The enzyme activities (mU/mg protein; mean +/- SEM) were
      similar (values for controls and schizophrenic patients, respectively) for PDHC
      (11.36 +/-1.5, 10.33 +/- 0.8), aconitase (1.06 +/- 0.1, 1.35 +/- 0.2), ICDH
      (31.70 +/- 2.7, 32.00 +/- 2.6), and KGDHC (2.62 +/- 0.4, 3.09 +/- 0.3). Separate
      analyses of the patients matched for age or postmortem interval gave similar
      conclusions. Cognitive dementia rating scores correlated poorly with activities
      of PDHC, aconitase, ICDH, and KGDHC. In one schizophrenic patient, activity of
      aconitase was undetectable, and in two others KGDHC activity was very low. Both
      had low activities of ICDH. A reduced activity of these enzymes in a subgroup is
      consistent with other data, suggesting that some patients with schizophrenia have
      abnormalities in brain mitochondria. However, in schizophrenia, unlike a number
      of neurodegenerative diseases, reductions in the activities of the key
      mitochondrial enzymes KGDHC and PDHC are not frequent.

PMID- 15456946
TI  - Characterization of the expression of key adenoviral receptors CAR and integrin
      beta3/beta5 subunits on the membrane of human NT2 neurons.
AB  - Expression of therapeutic gene products in differentiated human NT2 neurons
      (NT2/Ns) is being explored for ex vivo gene therapy of human neurological
      diseases. In this study we determined the efficiency of adenovirus (Ad)-mediated
      gene delivery into NT2/Ns and characterized the expression of several key
      receptors known to be required for efficient Ad-mediated gene delivery.
      Undifferentiated NT2 cells and NT2/Ns were infected by Ad expressing green
      fluorescent protein at an efficiency of 33% and 17%, respectively percentages
      much lower than the 92% infectivity obtained from a human non-neuronal cell line
      A549 cells. This relatively low infectivity of NT2/Ns might be caused by the
      extremely low expression of integrin subunit beta3 and the reduced expression of
      beta5 during differentiation. The expression of coxsackie-Ad receptor (CAR) was
      relatively high and remained constant during differentiation. Blocking CAR
      receptor using an antibody specific against CAR reduced Ad infectivity in a dose
      dependent manner. These observations suggest that modulating the expression of
      integrin subunits beta3/5 or the functional heterodimer alphavbeta3/5 in human
      NT2/Ns may enhance adenoviral infectivity of NT2/Ns.

PMID- 15456947
TI  - Salvage ifosfamide-doxorubicin chemotherapy in patients with recurrent
      nasopharyngeal carcinoma pretreated with Cisplatin-based chemotherapy.
AB  - This study evaluated the efficacy and toxicity of ifosfamide and doxorubicin
      chemotherapy regimen in Turkish patients with recurrent or metastatic
      nasopharyngeal carcinoma (NPC) previously treated with platinum-based
      chemotherapy. Twenty-one patients with recurrent or metastatic NPC previously
      treated with platinum-based chemotherapy as adjuvant or palliative treatments who
      received ifosfamide 2500 mg/m(2) d 1-3, mesna 2500 mg/m(2) d 1-3, doxorubicin 60
      mg/m(2) d 1, repeated every 21 d was retrospectively analyzed. Patients received
      a median number of three cycles of ifosfamide-doxorubicin (range: 1-6). Seven
      patients (33.3%) achieved partial response and no patient achieved complete
      response. Six (28.5%) had stable disease, whereas three (18.75%) had progressive
      disease. The median time to progression was 7.0 mo. Ifosfamide-doxorubicin
      regimen is an effective salvage regimen in patients with recurrent and metastatic
      NPC.

PMID- 15456948
TI  - Ocular metastases from breast carcinoma.
AB  - Intraocular metastases are the most common malignancy of the eye, and the primary
      cause is breast cancer. This is a retrospective analysis, which reports the
      clinical experience of eye metastases in 16 patients during the period of
      January, 1991, to December, 2002, who attended a tertiary referral center in
      Mexico City. Mean age at diagnosis was 40 yr (range 24-58). Most of patients were
      initially in clinical stage IIB-IV. Median time from breast cancer diagnosis to
      development of ocular metastases was 22.5 mo and from metastatic disease to
      ocular metastases was 10 mo. Ocular symptoms were decrease of visual acuity,
      ocular pain, nonspecific symptoms, proptosis, and palpebral edema. Three patients
      had bilateral ocular metastases. Fourteen patients were treated with radiation,
      and clinical response was documented in 4/15 eyes; ocular pain responded in three
      patients with this symptom. No ocular enucleations were performed. One patient
      developed glaucoma. No other major toxicities were documented. Median survival
      time was 26 mo and 25% of our patients were alive at a maximum follow-up of 90
      mo. This entity requires early recognition in order to preserve the visual
      function and quality of life of patients with breast cancer, since their
      prognosis has improved in recent years.

PMID- 15456949
TI  - Capecitabine monotherapy in patients with anthracycline- and taxane-pretreated
      metastatic breast cancer.
AB  - The selection of chemotherapeutic regimens is challenging for metastatic breast
      cancer (MBC) patients whose diseases have failed to respond to anthracyline and
      taxane. Capecitabine has advantages of oral administration and favorable toxicity
      profiles. This study was conducted to evaluate the efficacy of capecitabine and
      to identify the subgroup of patients who would potentially have benefit from
      capecitabine monotherapy in patients with anthracycline- and taxane-pretreated
      MBC. Female patients with MBC who had been previously treated with anthracycline
      and taxane received oral capecitabine 2500 mg/m(2) divided in two doses daily for
      2 wk with 1-wk rest period. Between September, 1999, and December, 2002, a total
      of 38 patients were enrolled. Among the 36 evaluable patients, one patient
      achieved a complete response (CR), 9 patients had partial responses (PRs), and 13
      patients had stable diseases (SDs). Response rate was 26% [95% confidence
      interval (CI), 12-40%] and the tumor control rate (TCR, CR+PR+SD) was 61% (95%
      CI, 45-77%). The median follow-up duration was 27.8 mo. The median duration of
      response was 8.9 mo, the median time to progression was 4.6 mo, and the median
      overall survival was 18.1 mo. The major toxicities were hand-foot syndrome,
      diarrhea, and emesis. There was no treatment-related death. The predictors of
      better overall survival were positivity of hormone receptor, disease-free
      survival longer than 1 yr, non-refractoriness to anthracycline, and fewer number
      (<or= 3) of involved organs. Capecitabine monotherapy is effective and well
      tolerated for MBC patients who had previously been treated with anthracycline and
      taxane. The TCR could predict overall survival as well as the objective response
      in this study, suggesting a possible role of TCR as a surrogate marker for
      survival in MBC patients on salvage chemotherapy. The patients who have
      relatively slow growing tumor and less tumor burden could have benefit from
      capecitabine monotherapy following anthracycline- and taxane-based chemotherapy.

PMID- 15456950
TI  - Second-Line docetaxel and gemcitabine combination chemotherapy in patients with
      non-small-cell lung cancer previously treated with platinum-based chemotherapy: a
      phase II trial.
AB  - Docetaxel has been the only single active agent against chemotherapy-pretreated
      non-small-cell lung cancer (NSCLC). The purpose of this phase II study was to
      evaluate the efficacy and safety of docetaxel combined with gemcitabine, another
      effective drug, in patients with NSCLC previously treated with platinum-based
      chemotherapy. Thirty-three patients were enrolled. Prior chemotherapy was
      cisplatin combined with etoposide in 24 patients and vinorelbine in 9 patients.
      Tumors were sensitive (n = 15), resistant (n = 9), and refractory (n = 9) to
      front-line chemotherapy. Treatment was docetaxel 85 mg/m(2) on d 1, and
      gemcitabine 1200 mg/m(2) on d 1 and 8, with cycles repeated every three weeks.
      Ten patients (30.3%, 95% CI: 15.6-48.7) achieved a partial response and 15
      (45.5%) stable disease. Responses were similar frequencies in platinum-sensitive
      and platinum-resistant/refractory tumors. With a median follow-up period of 5.7
      mo (range 1.6-20.0), the median and 6-mo event-free survival were 5.5 mo, 40.6%,
      respectively. Median and 6-mo overall survival were 7.3 mo and 52.7%. Patients
      with progressive disease to chemotherapy (p = 0.0008), higher LDH (p = 0.005),
      and NSE levels (p = 0.03) survived shorter than other patients. In patients
      refractory to prior chemotherapy, survival was poor as borderline significantly
      (p = 0.06). The major hematological toxicity was neutropenia. Grade III-IV
      neutropenia was noted in 14 (42%) patients, with three episodes of febrile
      neutropenia in 111 cycles. Docetaxel combined with gemcitabine is an active and
      safe second-line therapy for patients with NSCLC.

PMID- 15456951
TI  - Serum semicarbazide-sensitive amine oxidase (SSAO) activity correlates with VEGF
      in non-small-cell lung cancer patients.
AB  - Semicarbazide-sensitive amine oxidase (SSAO) is an enzyme associated with
      vascular systems in mammals. SSAO catalyzes the deamination of primary monoamines
      and has been suggested to be a risk factor in vascular disorders, e.g., diabetic
      vascular complications. The primary aim of the present study was to investigate
      if serum SSAO activity is associated with clinical parameters in non-small cell
      lung cancer (NSCLC) patients. Secondary aims were to investigate if there is a
      correlation between SSAO activity and the angiogenic factors vascular endothelial
      growth factor (VEGF) and basic fibroblast growth factor (bFGF).Thirty-three
      patients donated 231 serum samples. Detectable levels of bFGF, VEGF, and SSAO
      were observed in all patients. Serum SSAO activity was not statistically
      associated with survival (p = 0.35). A highly significant statistical correlation
      was found between SSAO activity and VEGF (p < 0.0001). No significant correlation
      between SSAO and bFGF was observed. We conclude that SSAO was not associated with
      survival in patients with NSCLC. However, a strong correlation between serum SSAO
      activity and the angiogenic factor VEGF was found that might implicate new
      aspects of the mechanisms controlling angiogenesis.

PMID- 15456952
TI  - Abnoba-viscum (mistletoe extract) in metastatic colorectal carcinoma resistant to
      5-fluorouracil and leucovorin-based chemotherapy.
AB  - A phase II trial was designed to determine whether mistletoe extract can induce
      objective tumor response in patients with metastatic colorectal cancer resistant
      to 5-fluorouracil and leucovorin (5FU/LCV)-based chemotherapy. Twenty-five
      patients (15 female, 10 male; median age 69 yr) were treated with commercially
      available mistletoe extract (Abnoba-viscum Quercus) given by three weekly
      subcutaneous injections with daily dose gradually increased from 0.15 to 15 mg
      plant extract. Treatment was discontinued if unacceptable toxicity developed or
      if the patient became bedridden. Median duration of treatment was 14 wk (range, 4
      66 wk). Treatment was continued in 14 patients until they became bedridden, and
      11 patients decided to discontinue the treatment after their illness progressed.
      Objective tumor response was not seen in any of the 25 patients (0%, 95%
      confidence interval 0-13.7%). Stable disease, lasting for a median of 2.5 mo
      (range, 1.5-7 mo), was noted in 21 (84%) patients. Median survival was 5.5 mo and
      symptomatic relief was reported by 10 (40%) patients. Toxicity was mild and
      included mainly local inflammatory reaction. In conclusion, mistletoe extract
      does not seem to be active in metastatic colorectal cancer resistant to 5FU/LCV
      in terms of objective tumor response.

PMID- 15456953
TI  - Weekly irinotecan (CPT-11) in 5-FU heavily pretreated and poor-performance-status
      patients with advanced colorectal cancer.
AB  - Irinotecan (CPT-11) is an effective drug in patients with advanced colorectal
      cancer (CRC). Little is known about its efficacy and safety in previously treated
      patients with poor performance status. We prospectively evaluated the antitumor
      efficacy and safety of CPT-11 monotherapy in this setting. Thirty-four patients
      with poor performance status (Karnofsky score between 60 and 80) and/or
      progressing on one or more previous 5-FU-based chemotherapy lines for advanced
      colorectal adenocarcinoma were enrolled in this study. Treatment consisted of
      irinotecan (CPT-11) at 100 mg/m(2) administered as a 60-min iv infusion every
      week for four consecutive weeks followed by a 2-wk rest period until disease
      progression or unacceptable toxicity. The overall objective response rate (WHO
      criteria) for the 34 patients included was 20.6% [95% confidence interval (CI):
      6.3%-34.9%]. Stable disease was obtained in 13 patients (38.2%) and 14 patients
      (41.2%) progressed. The median time to disease progression was 5.5 mo (range: 0.9
      17.5) and the median survival was 8.3 mo (95% CI: 1.7-16.9). Overall, weekly CPT
      11 was well tolerated with grade 3/4 neutropenia as the main hematological
      toxicity (11 patients: 32.4%; 14 infusions: 3.3%), and delayed diarrhea (10
      patients: 29.4%; 16 infusions: 3.8%) as the main grade 3/4 non-hematological
      toxicity. In conclusion, weekly CPT-11 at 100 mg/m(2) for four consecutive weeks
      followed by a 2-wk rest period showed antitumor efficacy and may be safely
      administered to heavily pretreated patients with advanced colorectal cancer and a
      poor performance status. Weekly CPT-11 monotherapy may be considered as a
      therapeutic option for this population of patients.

PMID- 15456954
TI  - Primary non-Hodgkin's lymphoma of the bone: a single institution experience.
AB  - Primary non-Hodgkin's lymphoma of the bone is an unusual entity. Twenty-five
      patients with diffuse large cell lymphoma of the bone were registered at the Tata
      Memorial Hospital (TMH) from August, 1991, to May, 2002. Pain at the local site
      and soft tissue swelling were the commonest symptoms. Involvement of the bones in
      the lower half of the body was more frequent than the bones in the upper half.
      Osteolytic lesions and an associated soft tissue mass were the common
      radiological findings. Nineteen patients received CHOP chemotherapy and five
      received COP chemotherapy. Twenty-three patients received involved field
      radiotherapy. The overall response to therapy was 96%. On follow-up, two patients
      had a nodal relapse. One patient died of progressive disease, and one patient
      died of cryptococcal meningitis. There were no deaths due to treatment-related
      toxicity. The mean progression free survival was 9.39 yr and the overall survival
      was 11.66 yr. The median overall survival has not been reached. At last follow
      up, 21 patients were being following up at TMH and are free of disease.
      CONCLUSION: Primary bone lymphoma is a malignancy that is highly curable with a
      combination of chemotherapy and radiotherapy.

PMID- 15456955
TI  - Intensive chemotherapy in the treatment of aggressive diffuse large B-cell
      lymphoma: malignant lymphoma.
AB  - The aim of the present study was to evaluate an intensive chemotherapy regimen in
      patients with diffuse large B-cell lymphoma and poor prognosis, as presence of
      high- or high-intermediate clinical risk, bulky disease, high levels of beta 2
      microgloblin, and more than two extranodal sites of involvement at diagnosis. One
      hundred previously untreated patients were treated with an intensive CEOP-Bleo
      regimen with increased doses of cyclophosphamide (1000 mg/m(2)) and epirubicin
      (120 mg/m(2)) in each cycle. Granulocyte colony-stimulating factors was employed
      to ameliorate severe granulocytopenia. Complete response was achieved in 79 cases
      (79%). With a median follow-up of 32.3 mo (range 10-45 mo) only seven patients
      have relapsed. Thus, actuarial curves at 3 yr, showed that event-free survival
      was 72%. Five died secondary to tumor progression, actuarial curves at 3-yr for
      overall survival were 75%. Toxicity was mild, granulocytopenia grade III or IV
      were observed in the 46% of the cycles; infection-related granulocytopenia was
      observed in 17%, but no fatality due to therapy was observed. Cardiac toxicity
      was mild, only seven patients showed a drop in left ejection ventricular
      function, but no symptomatic heart failure has been observed. The intensive CEOP
      Bleo regimen with increasing doses of cyclophosphamide and epirubicin is a useful
      and well-tolerated regimen in the treatment of poor prognosis diffuse large B
      cell lymphoma.

PMID- 15456956
TI  - Posttransplant lymphoma--a single-center experience of 500 liver
      transplantations.
AB  - BACKGROUND: Posttransplant lymphoproliferative disease (PTLD) is a serious
      complication after organ transplantation associated with a high mortality, and is
      often caused by a primary or reactivated Epstein-Barr virus (EBV) infection. The
      incidence of PTLD ranges from 1% to 10%, depending on the type of organ
      transplanted and the immunosuppressive regimens used. METHODS: In this
      retrospective study from a single center, 12 (2.4%) of 500 consecutive recipients
      of liver grafts developed lymphoma. Patient data were obtained by chart review.
      All diagnostic biopsies were reviewed by two hematopathologists. RESULTS: The
      median time between transplantation and the diagnosis of lymphoma was 19.5 (1.5
      148) mo. Nine of the patients had been treated with OKT-3 and/or ATG after the
      transplantation. Two patients had a pretransplant diagnosis of lymphoma. The PTLD
      was of high grade in all patients, and was associated with EBV in 6 of 9 examined
      cases. No relation with human herpesvirus-8 could be detected. In all patients,
      immunosuppression was reduced at the time of lymphoma diagnosis. Chemotherapy was
      used in all patients, mostly upfront but in one patient after lymphoma
      progression after reduction of immunosuppression. Nine patients also got
      antiviral therapy. Immunotherapy with the monoclonal antibody rituximab was used
      in one patient. Half of the patients are alive, in complete continuous remission,
      more than 4 yr after the lymphoma diagnosis. Two patients died of neutropenic
      sepsis, three of persistent lymphoma, and one of recurrent cirrhosis while in
      complete remission. CONCLUSIONS: PTLD is a significant complication in liver
      transplanted patients. Intensive chemotherapy can induce long-term remissions in
      a substantial number of patients. The role for monoclonal antibodies in this
      setting should be investigated further.

PMID- 15456957
TI  - Subtype selective interactions of somatostatin and somatostatin analogs with
      sst1, sst2, and sst5 in BON-1 cells.
AB  - Somatostatin is a polypeptide hormone acting as an inhibitor of pituitary,
      pancreatic, and gastrointestinal secretion through specific membrane receptors of
      which five subtypes have been cloned (sst(1-5)). Somatostatin analogs are used in
      the clinic to treat patients with excessive hormone production due to a
      neuroendocrine tumor. The aim of this study was to investigate the biological
      activity of three new somatostatin receptor subtype selective analogs (BIM-23926,
      sst(1)-selective; BIM-23120, sst(2)-selective; and BIM-23206, sst(5)-selective)
      in the human neuroendocrine tumor cell line, BON-1, which expresses sst(1),
      sst(2), and sst(5) natively. Somatostatin-14 and octreotide were used as
      reference substances. Forskolin-induced cAMP accumulation and chromogranin A
      (CgA) secretion were inhibited by BIM-23120, BIM-23206, and somatostatin-14 in a
      dose-dependent manner. Cholecystokinin (CCK-8) stimulated activation of mitogen
      activated protein (MAP) kinase was inhibited by BIM-23120 and BIM-23206, while
      BIM-23926 stimulated the activity. Selective BIM analogs showed a more efficient
      inhibitory effect on cAMP accumulation, CgA secretion, and MAP kinase activity
      than octreotide in BON-1 cells. This may be explained by the differences in
      affinity of the ligand to the receptor or by interaction between different sst
      subtypes. We conclude that increasing knowledge about sst physiology and
      expression in malignant disease indicates a need for new analogs that can be
      incorporated into the therapeutic arsenal.

PMID- 15456958
TI  - Oligonucleotide decoy mimicking alphaA-crystallin-binding protein 1 binding site
      on mouse Col2a1 enhancer stimulates transcription from the adjacent Col2a1
      promoter in chondrogenic ATDC5 cell.
AB  - A 48-bp sequence element in intron 1 of the alpha1(II) collagen gene (Col2a1)
      acts as an enhancer of Col2a1 transcription and contains binding sites for the
      transcription activator SOX9 and repressor alphaA-crystallin-binding protein 1
      (CRYBP1). We hypothesized that abrogating CRYBP1 binding should increase
      transcription from a promoter associated with the Col2a1 enhancer. We tested this
      hypothesis by cotransfecting an oligonucleotide (ODN) decoy for CRYBP1 and a
      luciferase-based reporter vector under the transcriptional control of the Col2a1
      promoter linked to the 100-bp enhancer in chondrogenic ATDC5 cells. As a control,
      we used decoy ODN corresponding to the SOX9 binding site. Transfection with
      CRYBP1 decoy increased luciferase activity by >2.5-fold in the absence or
      presence of insulin, whereas SOX9 decoy ODN decreased luciferase activity to
      about 50% under similar conditions. In addition, the repressive effect of
      interleukin-1 on Col2a1 transcription through decreasing SOX9 messenger
      ribonucleic acid (mRNA) expression and increasing CRYBP1 mRNA expression, was
      counteracted by CRYBP1 decoy ODN. These results provide a rationale for gene
      therapy in degenerative joint diseases by elevating Col2a1 expression in
      chondrocytes through oligomimetics of repressor binding sites.

PMID- 15456959
TI  - A novel gene homologous to teashirt is differentially expressed in neonatal mouse
      skin during development of hair follicles.
AB  - Neonatal mouse skin is useful for studying changes in gene expression during
      development of hair follicles, as the mitotic activity of skin cells changes
      shortly after birth. Using ribonucleic acid (RNA) differential display, a 261-nt
      message has been identified in the skin, specifically on d 3-5 but not on d 2
      after birth. Confirmation of its expression by ribonuclease protection assay
      showed that stronger expression is seen on d 3-5 compared with d 1-2. Using RNA
      ligase-mediated rapid amplification of 5' complementary deoxyribonucleic acid
      ends, we have successfully isolated a 3046-bp gene, which has 93% sequence
      homology to a mouse teashirt1 gene. Amino acid analysis showed that it has 74%
      identity to the mouse teashirt1 protein and possesses zinc-finger motifs 1, 2,
      and 3. In situ hybridization data revealed that it is mainly expressed in the
      follicle bulb, including dermal papilla and matrix cells. As the proliferation of
      bulb cells is important to follicle development during this period, the finding
      of its strong expression on d 3-5 suggests that the identified gene is a
      potential candidate for follicle growth.

PMID- 15456960
TI  - Comparison of nonviral transfection and adeno-associated viral transduction on
      cardiomyocytes.
AB  - Cardiomyocytes are terminally differentiated cells that to date have been
      characterized as poor targets for nonviral gene transfer. This study was
      therefore designed to determine the optimal nonviral gene transfer parameters in
      cell cultures of neonatal rat cardiomyocytes and to compare them with the
      efficiency of gene transfer using adeno-associated viral vectors (AAV).
      Transfection efficiency was measured by quantitative chloramphenicol
      acetyltransferase type I (CAT)-enzyme-linked immunosorbent assay and beta
      galactosidase staining, based on overexpression of reporter genes (CAT and LacZ).
      The efficiency of CAT/LacZ overexpression was assessed using the following
      techniques: (1) liposomal reagents, such as: FuGENE 6, LipofectAMINE 2000,
      LipofectAMINE PLUS, GenePORTER, Metafectene, and LipoGen; (2) electroporation and
      nucleofector techniques; and (3) an AAV2 vector harboring a lacZ reporter gene.
      Toxicity was monitored by total protein measurement and by analyzing cell
      metabolism. On average, Lipofectamine 2000 was the most effective nonviral method
      examined yielding consistently high transfection rates (8.1% beta-galactosidase
      positive cells) combined with low toxicity. Electroporation also resulted in high
      transfection values (7.5%); however, cellular toxicity was higher than that of
      Lipofectamine 2000. Finally, transduction with AAV2 vectors provided the highest
      levels of transduction (88.1%) with no cellular toxicity. We conclude that
      although transduction with AAV is more efficient (88.1%), transfections with
      nonviral techniques, when optimized, may provide a useful alternative for
      overexpression of therapeutic genes in neonatal cardiomyocytes.

PMID- 15456961
TI  - Synthesis and assembly of SIVmac Gag p27 capsid protein cholera toxin B subunit
      fusion protein in transgenic potato.
AB  - A deoxyribonucleic acid (DNA) fragment encoding the cholera toxin B subunit (CTB)
      was linked 5' to the simian immunodeficiency virus (SIVmac) Gag p27 capsid gene
      (CTB-Gag). The fusion gene was transferred into Solanum tuberosum cells by
      Agrobacterium tumefaciens-mediated transformation methods and transformed plants
      regenerated. The CTB-Gag gene fusion was detected in transformed potato leaf
      genomic DNA by polymerase chain reaction-mediated DNA amplification. The results
      of immunoblot analysis with anti-CTB and anti-Gag antibodies verified the
      synthesis of biologically active CTB-Gag fusion protein in transformed leaf and
      tuber tissues. Synthesis and assembly of the CTB-Gag fusion protein into
      oligomeric structures of pentamer size was confirmed by GM1-ganglioside-enzyme
      linked immunosorbent assay (GM1-ELISA) of transformed potato tuber tissue
      extracts. The binding of CTB-Gag fusion protein oligomers to intestinal
      epithelial cell membrane receptors quantified by GM1-ELISA showed that CTB-Gag
      fusion protein made up approx 0.016-0.022% of the total soluble tuber protein.
      The synthesis of CTB-Gag monomers and their assembly into biologically active CTB
      Gag fusion protein oligomers in potato tuber tissues provides the opportunity for
      employment of the carrier and adjuvant properties of CTB for the development of
      edible plant-based subunit mucosal vaccines for enhanced mucosal immunity against
      SIV in macaques.

PMID- 15456962
TI  - Fluorescent detection of differentially expressed cDNA using SYBR gold nucleic
      acid gel stain.
AB  - We describe herein a modified differential gene display (DGD) technique that can
      be rapidly and simply performed and that eliminates the need for radioactivity by
      fluorescent visualization of complementary deoxyribonucleic acid (cDNA) bands
      with SYBR gold nucleic acid gel stain. To streamline the DGD procedure, a number
      of modifications were employed. Ribonucleic acid isolated from differentially
      treated populations of human trabecular bone-derived mesenchymal progenitor cells
      was reverse-transcribed into cDNA using oligo-dT primer, and subsequent
      amplification of differentially expressed cDNAs was done using arbitrary 25-mer
      primers and oligo-dT9 30-mer primers. Moderate-sized nondenaturing 6%
      polyacrylamide gels (30 x 20 cm) of 1.5-mm thickness were used for easier
      handling and increased sample loading capacity. Gels were subjected to
      electrophoresis overnight, stained with SYBR gold, and visualized and
      photographed using a commercially available gel imager. DNA bands ranging in size
      from 100 to 400 bp were visualized directly on an ultraviolet transilluminator,
      excised from the gel, and reamplified. The cDNA amplicons were subcloned,
      sequenced, and gene sequences were identified by a Basic Local Alignment Search
      Tool of genomic databases. Overall, this rapid and functional method proved quite
      effective for identification of novel genes that may be of interest in studies of
      cartilage and bone differentiation.

PMID- 15456963
TI  - Resistance to macrolide, lincosamide, streptogramin, ketolide, and oxazolidinone
      antibiotics.
AB  - Macrolides have enjoyed a resurgence as new derivatives and related compounds
      have come to market. These newer compounds have become important in the treatment
      of community-acquired pneumoniae and nontuberculosis-Mycobacterium diseases. In
      this review, the bacterial mechanisms of resistance to the macrolide,
      lincosamide, streptogramin, ketolide, and oxazolidinone antibiotics, the
      distribution of the various acquired genes that confer resistance, as well as
      mutations that have been identified in clinical and laboratory strains are
      examined.

PMID- 15456964
TI  - Recent advances in gel-based proteome profiling techniques.
AB  - This review focuses on recent developments in gel-based proteomics techniques. By
      combining traditional sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      (SDS-PAGE) and two-dimensional gel electrophoretic techniques with recent
      advances in protein labeling using different classes of molecules (i.e.,
      fluorescent dyes, chemical probes, radioisotopes), new technologies have been
      developed that allow for high-throughput studies of proteins at the whole
      proteome scale.

PMID- 15456965
TI  - End labeling procedures: an overview.
AB  - There are two ways to label a DNA molecular; by the ends or all along the
      molecule. End labeling can be performed at the 3'- or 5'-end. Labeling at the 3'
      end is performed by filling 3'-end recessed ends with a mixture or labeled and
      unlabeled dNTPs using Klenow or T4 DNA polymerases. Both reactions are template
      dependent. Terminal deoxynucleotide transferase incorporates dNTPs at the 3' end
      of any kind of DNA molecule or RNA. Labels incorporated at the 3'-end of the DNA
      molecule prevent any further extension or ligation to any other molecule, but
      this can be overcome by labeling the 5'-end of the desired DNA molecule. 5'-end
      labeling is performed by enzymatic methods (T4 polynucleotide kinase exchange and
      forward reactions), by chemical modification of sensitized oligonucleotides with
      phosphoroamidite, or by combined methods. Probe cleanup is recommended when high
      background problems occur, but caution should be taken not to damage the attached
      probe with harsh chemicals or by light exposure.

PMID- 15456966
TI  - Ten-year anniversary of the Faculty of Public Health of Kaunas University of
      Medicine.

PMID- 15456967
TI  - [Values and goals of medicine and health care].
AB  - Discussions about the goals of medicine and health care have significantly
      increased through the last decade of the past century. This was determined by the
      highly increased extent of health care, scarce health care resources, fundamental
      changes of health care technologies and well-established market relationships in
      health care. For a long time medicine attempted to achieve three main goals: to
      save and prolong life, fight and prevent diseases, reduce pain and sufferings. In
      the result of development of medicine the previous goals became rather
      problematic. Technological progress of medicine of the second half of the 20th
      century has implemented the believing, that medicine is able to prolong the life
      of human without restrictions. Ageing population has started expecting from
      medicine not only the saving of life and health enhancement, but also prolonging
      of life, since the mentioned is tended to be more socioeconomic, not medical,
      problem. Nowadays discussion about the goals of health care comes from the
      doubts, if the questions for medicine really have medical background. Often the
      society tries to escape from number of social problems medicalizing them.
      Spiritual and social problems of human are often supposed to be as medical ones,
      thus it is crucial to separate the main goals of medicine, which represent its
      values and targets, from the secondary ones, related to social or individual
      welfare, crime, dilemmas of poverty or morality. The aim of the article is to
      reveal the key values of medicine and health care, which determine the goals of
      medicine and health care.

PMID- 15456968
TI  - Drug addiction maintenance treatment and quality of life measurements.
AB  - Quality of life measurements are increasingly incorporated into trials of
      pharmaceuticals. This can be applied to a wide range of medical areas including
      drug-addiction maintenance treatment programs. Maintenance treatment has been
      demonstrated to be an effective treatment for opioid addiction but still lacks
      quality of life specific measures to measure the maintenance program effects and
      until now there have been only few attempts to assess the impact of opioid
      dependence and its treatment on the drug-addicted patients' quality of life. The
      aim of this article is to describe quality of life concept, measurement
      instruments, selection criteria and its applicability in the drug addiction
      maintenance studies.

PMID- 15456969
TI  - Parathyroid hormone--possible future drug for orthopedic surgery.
AB  - Parathyroid hormone naturally secreted by the parathyroid glands is a potent
      anabolic agent for bone. Parathyroid hormone is primarily thought of as a
      catabolic protein involved in the physiologic release of calcium from bone.
      Whereas during recent years, a number of animal studies and clinical trials have
      demonstrated that intermittent parathyroid hormone administration induces
      anabolic effects on both cancellous and cortical bone, enhances bone mass and
      increases mechanical strength of the bones. Most of the studies, both animal and
      human, have addressed the treatment of osteoporosis and parathyroid hormone
      represents an important new advance in the therapy of osteoporosis. Few studies
      have investigated the effect of intermittent parathyroid hormone treatment in the
      field of orthopedics on fracture healing and fixation of orthopedic implants. The
      results of those studies indicated an enhancement of fracture healing, faster
      bone repair and better fixation of the implant. Recently there were few animal
      studies started to investigate the effects of parathyroid hormone treatment on
      bone formation in regenerated and surrounding bone of distracted callus during
      limb lengthening. Distraction osteogenesis is a technique for bone lengthening
      that is widely used clinically and experimentally. Newly forming bone during
      distraction osteogenesis is expected to be an appropriate pattern for parathyroid
      hormone anabolic effect. Preclinical studies as well as clinical trials suggest
      that parathyroid hormone might be useful as a stimulator of bone formation
      whereas a lot of questions regarding parathyroid hormone therapy remain
      unanswered and require further experimental studies and investigations.

PMID- 15456970
TI  - Alterations of platelet aggregation while treating cardiac arrhythmias with
      radiofrequency ablation.
AB  - OBJECTIVE: To find out if radiofrequency ablation as method of treatment of
      cardiac arrhythmia influences platelet aggregation and if intensity of this
      process depends on the number of radiofrequency ablation episodes for one
      patient. MATERIAL AND METHODS: We analyzed platelet aggregation before, right
      after and in 24 hours after radiofrequency ablation in whole blood and platelet
      rich plasma in 39 cases with cardiac arrhythmias. Adenosine diphosphate and
      adrenaline were used for aggregation induction. Three groups of patients were
      formed based on the number of radiofrequency ablation episodes: A-- <10, B--10
      20, C-- >20 for one patient. RESULTS: We detected a decrease in spontaneous,
      adenosine diphosphate and adrenaline induced platelet aggregation in plasma right
      after radiofrequency ablation, and also the same tendency was noted in adenosine
      diphosphate induced aggregation in whole blood. In 24 hours after radiofrequency
      ablation platelet aggregation tended to return to pre-radiofrequency ablation
      levels. Based on the number of radiofrequency ablation episodes we detected
      significant changes in spontaneous and adrenaline-induced aggregation in plasma.
      In group A adrenaline induced aggregation after radiofrequency ablation increased
      by 0.4%, in group B it decreased by 15.7% and in group C it decreased by 19.4%
      from pre-radiofrequency ablation level (p<0.05, between groups A and C).
      Spontaneous platelet aggregation after radiofrequency ablation decreased in group
      A 41.9%, in group B--20.8% and in group C--18.4% from pre-radiofrequency ablation
      level (p<0.05 between groups A and C). The greater decrease in adenosine
      diphosphate induced aggregation in plasma and in whole blood was detected in the
      group with larger number of radiofrequency ablation episodes. CONCLUSIONS: This
      study found that platelet aggregation decreased in plasma and in whole blood
      after radiofrequency ablation. And this alteration was significant in groups B
      and C, when the number of radiofrequency ablation episodes were >10. In 24 hours
      platelet aggregation increased again to pre- radiofrequency ablation level.

PMID- 15456971
TI  - Closed tympanoplasty in middle ear cholesteatoma surgery.
AB  - OBJECTIVE: To determine the effect of closed tympanoplasty surgery for middle ear
      cholesteatoma and to compare the postoperative results with the outcomes of canal
      wall-down mastoidectomy. METHODS: Seventy patients with middle ear cholesteatoma
      were involved in the study. Pneumo-otoscopy, pure-tone audiometry, anamnestic and
      clinical data were evaluated before the surgery. Modified radical mastoidectomy
      was performed for 31 patients. Thirty-nine patients were treated with closed
      tympanoplasty surgery, including intact canal wall mastoidectomy, endaural
      atticotomy, lateral attic and aditus wall reconstruction and tympanoplasty. The
      follow-up examination was carried out 12 months after the surgery. The recurrence
      of cholesteatoma, otorrhea and hearing level were evaluated postoperatively.
      RESULTS: Otorrhea was estimated in 4 cases (10.3%) after closed tympanoplasty
      surgery and in 6 cases (19.4%) after modified radical mastoidectomy. Among the
      patients who were operated using closed tympanoplasty technique the middle ear
      cholesteatoma recurrence rate was 12.8% and among those, who underwent modified
      radical mastoidectomy recurrent disease occurred in 9.7% of the cases. The
      hearing improvement was found in 15 cases (38.46%) after closed tympanoplasty,
      while there was no hearing improvement after modified radical mastoidectomy.
      CONCLUSIONS: We conclude that despite the fact, that cholesteatoma recurrence
      rate after closed tympanoplasty is relatively high, this surgical method permits
      to preserve adequate hearing level and releases from postoperative cavity care
      problems as compared with modified radical mastoidectomy.

PMID- 15456972
TI  - Lipoma of the greater omentum in a child.
AB  - Lipoma of the greater omentum is observed very rarely, particularly in the
      childhood. We report a case of large 10x11x8 cm asymptomatic lipoma of the
      greater omentum, which was diagnosed incidentally. Well-encapsulated mass with a
      homogeneous internal structure and high echogenicity--these signs of ultrasound
      and computed tomography allowed us to suggest a lipoma. At laparotomy lipoma of
      greater omentum in torsion was found. The excision of the tumor and omentectomy
      was performed. The histopathological diagnosis was lipoma with focal necrosis
      areas.

PMID- 15456973
TI  - Microvillous inclusion disease.
AB  - Congenital defects in the intestinal mucosa can provoke diarrhea in the neonatal
      period. This kind of diarrhea is difficult to treat and the outcome is bad if
      intestinal transplantation is not done. We describe the case of newborn female
      with severe protracted secretory diarrhea, which started after first oral intake
      of breast milk. The newborn presented with severe dehydration and persistent
      metabolic acidosis though potential treatment was not stopped. Endoscopy with the
      biopsies from the distal part of duodenum mucosa was done on the third week of
      life. Histological examination revealed the pathological mucosa with the total
      microvillous atrophy, surface epithelium thinning and histochemical PAS (Periodic
      acid-Schiff reaction) positivity of enterocytes apical region. These changes are
      typical for rare microvillous inclusion disease. When the diagnosis of
      microvillous inclusion disease is made, the only treatment is total parenteral
      nutrition and intestinal transplantation.

PMID- 15456974
TI  - Experimental evidence on possibility to radiosensitize aggressive tumors by
      porphyrins.
AB  - Two murine experimental tumor models of different aggressiveness (murine Ehrlich
      ascitic carcinoma and MH-22A hepatoma) were used to investigate the
      radiosensitization by porphyrins. Data obtained clearly indicate that
      hematoporphyrin dimethyl ether, photofrin and hematoporphyrin derivative exert
      some radiosensitizing properties which are in clear correlation with purity of
      the compound. Of interest to note, that just aggressive Ehrlich ascitic carcinoma
      was radiosensitized to gamma-radiation, whereas no signs of radiosensitization
      were observed in MH-22A hepatoma tumor. Data obtained support the idea, that
      dicarboxylic porphyrins, being ligands of peripheral benzodiazepine receptors
      (responsible for proliferation and highly expressed in aggressive tumors) might
      induce several sublethal injuries in the cell which further work in concert with
      ionizing radiation producing synergistic interaction of two antiproliferative
      factors.

PMID- 15456975
TI  - Health inequalities in Lithuania: education and nutrition habits.
AB  - The aim of the study was to evaluate the associations between food behavior and
      educational level among Lithuanian adult population. Five health behavior surveys
      were carried out within the international Finbalt Health Monitor project in 1994
      2002. For every survey the national random sample of 3000 inhabitants aged 20-64
      was taken from the National Population Register. The study material was collected
      through mailed questionnaires covering sociodemographic characteristics and some
      nutrition habits. The respondents were categorized according to the level of
      education into three groups: persons having incomplete secondary, secondary and
      university education. Multiple regression analysis was used for evaluation of
      associations between level of education and nutrition habits. The persons with
      university education have a healthier diet than those with incomplete secondary
      education. The consumption of fish, vegetables and fruit, use of vegetable oil
      for cooking, was substantially higher in those with university education as
      compared to persons with incomplete secondary education. The proportion of
      persons drinking whole milk was the highest among the low educated men and women.
      The high-educated women consumed meat less often than those with incomplete
      secondary education did. However, persons with university education preferred
      butter on bread. The high-educated men consumed cheese daily more often than
      those with low education. The positive trends in nutrition habits of Lithuanians
      were observed between 1994 and 2002. However, educational differences in
      nutrition habits still remain significant. In conclusion, alongside with other
      health interventions, the programs aimed at reducing inequalities in health
      should consider the educational differences in nutrition habits of Lithuanians
      paying more attention to less educated persons.

PMID- 15456976
TI  - Changes in health behavior of Lithuanian adolescents and adults over 1994-2002.
AB  - The aim of the study was to investigate the time trends in health behavior during
      the period 1994-2002 in Lithuanian schoolchildren and adult population. The data
      on smoking, alcohol drinking, consumption of fresh vegetables and fruits,
      physical activity habits are presented in the article. The study material was
      collected in 1994, 1998 and 2002 within the framework of two international
      projects: Health Behavior in School-aged children coordinated by WHO and Finbalt
      Health Monitor assessing health behavior among adults in Finland and Baltic
      countries. The data of our study showed that since 1994 prevalence of smoking
      substantially increased among Lithuanian teenagers aged 11-15 years and adult
      women. The increase in alcohol consumption was recorded in schoolchildren as well
      as in adult population. The adults started eating fresh vegetables and fruits
      more frequently while the usage of fresh fruits among teenagers declined. In 2002
      70% of schoolboys and 45% of schoolgirls were physically active. There were no
      changes in physical activity among teenagers over the period of the study. The
      proportion of physically active persons in adult population has increased since
      1994. CONCLUSION: The health behavior is unhealthy in large proportion of
      Lithuanian teenagers and adults. The negative trends in health behavior
      especially among teenagers may increase the risk of noncommunicable diseases in
      Lithuanian population. Therefore the elaboration and implementation of effective
      health promotion programs, which should start in early childhood and would be
      adopted to the needs of different age groups, is urgently needed.

PMID- 15456977
TI  - [Importance of the modern health management for the success of health reform in
      Lithuania].
AB  - Reform of the Lithuanian health system is a challenging process. The aim of this
      article is to assess the role of health managers in the process of health reform,
      evaluating the perception of health management and their training needs, as the
      possible determinants for the success of the reform. The results of several
      questionnaire surveys of Lithuanian health managers, particularly the one carried
      out in 2002 are used. The studies demonstrate great diversity in the conceptual
      understanding of health management, with prevailing rational and technical
      understanding. This might be associated with the rapid structural and
      organizational changes in the early stages of health reform and insufficient
      involvement of health managers in the planning and management of changes. General
      management, health policy, economic and law are considered as the most important
      study areas for health managers. The major lacking knowledge is in the subjects
      of law, economics and health financing. Health managers should act as mediators
      between politicians and health professionals. Enlargement of the area of
      competences, increasing autonomy in solving problems and meeting of the training
      needs of health managers is essential.

PMID- 15456978
TI  - Occupational health problems in modern work environment.
AB  - Analysis of occupational health problems in Lithuania and their relation to
      factors of modern work environment is presented. The article analyses the health
      of transport workers, airlines pilots and stewards, video display terminal
      workers and its relation to work environment. OBJECTIVE: To investigate and
      evaluate influence of changing occupational environment to workers' health.
      MATERIAL AND METHODS: Complex evaluation including several enterprises with
      different work profile and conditions. Evaluation of work environment, assessment
      of psychophysiological and ophthalmological data of workers as well as morbidity
      studies were performed. RESULTS: Occupational environment of transport workers is
      related with high levels of noise, vibration, mercury, carbon monoxide, welding
      aerosols, and dust. Main diseases for transport workers are upper respiratory
      tract and lung diseases, accidents, cardiovascular and musculoskeletal disorders.
      Cases of temporal morbidity for pilots and stewards are upper respiratory tract
      and lung diseases, accidents, intoxications and nervous system diseases. The main
      effects of video display terminal on operators' health are vision fatigue and
      musculoskeletal disorders. Ophthalmologic symptoms and vision fatigue are related
      to changes in eyes and central nervous system fatigue, as well as syndrome of
      "dry eyes". CONCLUSIONS: Changeable work environment is affecting employees'
      health with specific changes, which depend upon work character, experience and
      worker's age.

PMID- 15456979
TI  - [Methods of suicides in Lithuania and their associations with demographic
      factors].
AB  - Methods of completed suicides in relation to gender, age and place of residence
      and their changes in Lithuania during 1993-1997 and 1998-2002 were analyzed in
      this study. Data on completed suicides (n=16147) was compiled from the
      computerized database of the Lithuanian Department of Statistics. Hanging was the
      most common method of completed suicides in Lithuania. Proportion of hanging
      among the other methods of suicides increased from 87.3% during 1993-1997 till
      90.1% during 1998-2002. Proportion of hanging increased most notably among girls
      aged 10-19. Hanging, as the method of suicide, was more prevalent among males in
      comparison to females and among rural residents in comparison to the urban
      population. Proportion of hanging had the increasing tendency with an increase of
      age. The next most prevalent method of suicide among males was firearm, while
      among females--poisoning, jumping from the height and drowning. Different types
      of poisoning were more prevalent among adolescents, particularly among girls, in
      comparison to the adult population. Poisoning and jumping from the height were
      more common among urban males and females if compared to the rural population.

PMID- 15456980
TI  - [150th birth anniversary of Izidor Brennsohn, Latvian historian of medicine and
      researcher of Lithuanian anthropology].
AB  - This publication is dedicated to the 150th birth anniversary of a famous German
      writing Latvian physician, historian of medicine, and anthropologist of Jewish
      descent Izidor Brennsohn, and to his ties with Lithuania. I. Brennsohn's works on
      physicians and the development of health care in Kurland, Livland, and Estland
      laid the foundations for the contemporary historiography of medicine in Latvia
      and Estonia. To a certain extent, these works could also be viewed as a digest of
      the sources of Lithuanian history of medicine, especially in regard to the
      regions on the boarder with Latvia, as well as to various personalities. However,
      Brennsohn's most important link with Lithuania was his doctoral thesis "On
      Lithuanian anthropology" ("Zur Anthropologie der Litauer"), defended at Dorpat
      (Tartu) University in 1883. It was one of the first works dealing with Lithuanian
      ethnic anthropology as a whole. Although, material of thesis could not be used
      for wider generalizations, still, it is one of rare and valuable 19th century
      sources of Lithuanian anthropology. Brennsohn's legacy deserves greater attention
      from people researching medical history in Lithuania.

PMID- 15456981
TI  - [Conservative ways to treat cancer pain].
AB  - Cancer pain is a major problem for cancer patients, as about 80 percent patients
      with advanced cancer declare pain as their main symptom. The causes of the pain
      are very different: due to the main tumor, its metastases, anticancer treatment,
      debility caused by the cancer or other diseases. The cancer pain relief algorithm
      is proposed in the article, including determination of the cause, type, intensity
      of pain, its pharmacological and non-pharmacological management, opioid rotation
      rules, treatment of adverse drug reactions, etc.

PMID- 15456982
TI  - Altruism, altruistic punishment and social investment.
AB  - The concept of altruism is used in very different forms by computer
      scientists,economists, philosophers, social scientists, psychologists and
      biologists. Yet, in order to be useful in social simulations, the concept
      "altruism" requires a more precise meaning. A quantitative formulation is
      proposed here, based on the cost/benefit analysis of the altruist and of society
      at large. This formulation is applied in the analysis of the social dynamic
      working of behaviors that have been called "altruistic punishments", using the
      agent based computer model Sociodynamica. The simulations suggest that
      "altruistic punishment" on its own cannot maintain altruistic behaviors.
      "Altruistic behavior" is sustainable in the long term only if these behaviors
      trigger synergetic forces in society that eventually make them produce benefits
      to most individuals. The simulations suggest however that "altruistic punishment"
      may work as a "social investment", and is thus better called "decentralized
      social punishment". This behavior is very efficient in enforcing social norms.
      The efficiency of decentralized social punishment in enforcing norms was
      dependent on the type of labor structured of the virtual society. I conclude that
      what is called "altruistic punishment" emerges as a type of social investment
      that can evolve either through individual and/or group selection, as a successful
      device for changing or enforcing norms in a society. Social simulations will help
      us in better understanding the underlying dynamic working of such devices.

PMID- 15456983
TI  - Protein folding and evolution are driven by the Maxwell Demon activity of
      proteins.
AB  - In this paper we propose a theoretical model of protein folding and protein
      evolution in which a polypeptide (sequence/structure) is assumed to behave as a
      Maxwell Demon or Information Gathering and Using System (IGUS) that performs
      measurements aiming at the construction of the native structure. Our model
      proposes that a physical meaning to Shannon information (H) and Chaitin's
      algorithmic information (K) parameters can be both defined and referred from the
      IGUS standpoint. Our hypothesis accounts for the interdependence of protein
      folding and protein evolution through mutual influencing relationships mediated
      by the IGUS. In brief, IGUS activity in protein folding determines long term
      tendencies that emerge at the evolutionary time-scale.Thus, protein evolution is
      a consequence of measurements executed by proteins at the cellular level, where
      the IGUS imposes a tendency to attain a highly unique stable native form that
      promotes the updating of the information content. The folding kinetics observed
      is, thus, the outcome of an evolutionary process where the polypeptide-IGUS
      drives the evolution of its linear sequence. Finally, we describe protein
      evolution as an entropic process that tends to increase the content of mutual
      algorithmic information between the sequence and the structure. This model
      enables one: 1. To comprehend that full determination of the three-dimensional
      structure by the linear sequence is a tendency where satisfaction is only
      possible at thermodynamic equilibrium.2. To account for the observed randomness
      of the amino acid sequences. 3. To predict an alternation of periods of selection
      and neutral diffusion during protein evolutionary time.

PMID- 15456984
TI  - Current issues in statistics and models for ecotoxicological risk assessment.
AB  - A review is given on statistical and modelling issues in ecotoxicology. The
      issues discussed are: 1. How to estimate an (almost) no effect concentration
      chemicals in the laboratory. 2. Combining single-species acceptable effect levels
      to an acceptable effect level for a multi-species ecosystem. 3. The combined
      effect of exposure to several chemicals. 4. Bioavailability in the natural
      environment and food-web models. Most current procedures in setting standards
      allow the environmental concentration to be above the acceptable effect
      concentration for a small fraction of the species. It is shown that a
      considerable part of the fraction of the affected species will suffer a severe
      effect.

PMID- 15456985
TI  - Comorbidity in psychiatric and chronic physical disease: autocognitive
      developmental disorders of structured psychosocial stress.
AB  - Applying a 'necessary condition' communication theory formalism roughly similar
      to that of Dretske, but focused entirely on the statistical properties of long
      sequences of signals emitted by the interacting cognitive modules of human
      biology, we explore the regularities apparent in comorbid psychiatric and chronic
      physical disorders using an extension of recent perspectives on autoimmune
      disease. We find that structured psychosocial stress can literally write a
      distorted image of itself onto child development, resulting in a life course
      trajectory to characteristic forms of comorbid mind/body dysfunction affecting
      both dominant and subordinate populations within a pathogenic social hierarchy.

PMID- 15456986
TI  - A recipe for unconventional evenness measures.
AB  - The degree to which abundances are evenly divided among the species of a given
      community is a basic property of any biological community. Several evenness
      indices have thus far been proposed in ecological literature. However, despite
      their vast potential applicability in ecological research, none seems to be
      generally preferred. In this paper, I first summarize the basic requirements that
      evenness measures should meet to adequately behave in ecological studies. Then, I
      discuss the major drawbacks of these requirements and propose an alternative
      family of measures that are based on the notion of specificity used in fuzzy set
      theory for measuring the uncertainty associated with a fuzzy set.

PMID- 15456987
TI  - Causes and consequences of eukaryotization through mutualistic endosymbiosis and
      compartmentalization.
AB  - This paper reviews and extends ideas of eukaryotization by endosymbiosis. These
      ideas are put within an historical context of processes that may have led up to
      eukaryotization and those that seem to have resulted from this process. Our
      starting point for considering the emergence and development of life as an
      organized system of chemical reactions should in the first place be in accordance
      with thermodynamic principles and hence should, as far as possible, be derived
      from these principles. One trend to be observed is the ever-increasing complexity
      resulting in several layers of compartmentalization of the reaction system,
      either spatial (of which the eukaryotic cell is an example), or functional (as in
      the gradually deepening distinction between metabolic, enzymatic and information
      storing functions within the cell). One of the causes of this complexification of
      living systems will have been the changes in environmental conditions,
      particularly the geochemical impoverishment of the biosphere during geological
      history, partly brought about by living systems themselves, and partly by the
      trend towards increasing efficiency and specificity of the reactions that occur.

PMID- 15456988
TI  - Coffee, decaffeinated coffee, tea and cancer of the colon and rectum: a review of
      epidemiological studies, 1990-2003.
AB  - The literature from 1990 to 2003 on the relation between coffee, decaffeinated
      coffee, tea and colorectal cancer risk has been reviewed. For the relation with
      coffee, three cohort (517 total cases) and nine case-control studies (7555 cases)
      analysed colon cancer; three cohort (307 cases) and four case-control studies
      (2704 cases) rectal cancer; six case-control studies (854 cases) colorectal
      cancer. For colon cancer most case-control studies found risk estimates below
      unity; the results are less clear for cohort studies. No relation emerged for
      rectal cancer. A meta-analysis, including five cohort and twelve case-control
      studies, reported a pooled relative risk of 0.76 (significant). Any
      methodological artefact is unlikely to account for the consistent inverse
      association in different countries and settings. Plausible biological
      explanations include coffee-related reductions of cholesterol, bile acids and
      neutral sterol secretion in the colon; antimutagenic properties of selected
      coffee components; increased colonic motility. Decaffeinated coffee was not
      related to either colon or rectal cancer in three case-control studies. No
      overall association between tea and either colon or rectal cancer risk emerged in
      seven cohort (1756 total cases of colon, 759 of rectal and 60 of colorectal
      cancer) and 12 case-control studies (8058 cases of colon, 4865 of rectal, 604 of
      colorectal cancer).

PMID- 15456989
TI  - Occupation and bladder cancer risk in a population-based case-control study in
      New Hampshire.
AB  - OBJECTIVE: To identify occupations with excess bladder cancer risk in New
      Hampshire, where bladder cancer mortality rates have been elevated for decades.
      METHODS: Lifetime occupational histories were obtained from interviews with 424
      cases and 645 controls in a population-based case-control study. Unconditional
      logistic regression models were used to estimate odds ratios (Ors) and 95%
      confidence intervals (CI) for each occupation, adjusted for age and smoking.
      Analyses by duration of employment were carried out and interactions with smoking
      were examined. RESULTS: Male tractor-trailer truck drivers had an elevated risk
      for bladder cancer (OR = 2.4, CI = 1.4-4.1), with a significant positive trend in
      risk with increasing duration of employment (P (trend) = 0.0003). Male
      metal/plastic processing machine operators also had a significant excess (OR =
      4.9, CI = 1.6-15.1), attributable mainly to molding/casting machine operators (OR
      = 16.6, CI = 2.1-131). Elevated risk was also observed for male fabricators,
      assemblers, and hand workers (OR = 1.8, CI = 1.0-3.4). Women in certain sales
      occupations (sales clerks, counter clerks, and cashiers) had a significant excess
      risk (OR = 2.2, CI = 1.3-3.9) and a significant trend with duration of employment
      (P (trend) = 0.016), as did female health service workers (OR = 4.1, CI = 1.6
      10.7; P (trend) = 0.014). There was a positive interaction between smoking and
      employment as a health service worker (p = 0.036). CONCLUSIONS: These findings
      are generally consistent with previous studies. Elevated risks for male
      molding/casting machine operators, female salesworkers, and female health service
      workers, especially those with a history of smoking, require further
      investigation.

PMID- 15456990
TI  - Tobacco and alcohol consumption and the risk of non-Hodgkin lymphoma.
AB  - OBJECTIVE: The aim was to test whether non-Hodgkin lymphoma (NHL) is associated
      with smoking or alcohol. METHODS: A case-control study recruited NHL cases aged
      18-64 in parts of England between 1998 and 2001. One control was matched to each
      case on sex, date of birth and area of residence. Self-reported histories of
      tobacco and alcohol consumption were collected during face-to-face interviews.
      RESULTS: Among 700 cases and 915 controls, no association of smoking with the
      risk of NHL was observed [odds ratio (OR) = 1.04, 95% confidence interval (CI):
      0.85-1.28]. Risks were not raised with age started smoking, number of years
      smoked, and number of years stopped smoking. Compared with persons who drank
      alcohol once or twice a week, neither abstainers (OR = 1.03, 95% CI: 0.64-1.67),
      nor consumers of alcohol one to five times a year (OR = 1.35, 95% CI: 0.95-1.93),
      one to two times a month (OR = 1.20, 95% CI: 0.87-1.65), three to four times a
      week (OR = 0.82, 95% CI: 0.62-1.10), or most days (OR = 0.94, 95% CI: 0.70-1.25)
      increased their risk of developing NHL. Average daily volume or high occasional
      alcohol consumption were not associated with NHL. CONCLUSIONS: NHL was not
      associated with smoking or alcohol, but collaborative studies could further
      investigate the risks of rarer WHO subtypes following these exposures.

PMID- 15456991
TI  - Cataract extraction and risk of breast cancer.
AB  - OBJECTIVE: To prospectively examine the association between cataract extraction
      and breast cancer risk among 66,782 postmenopausal women who were 50 years or
      older in the Nurses' Health Study cohort from 1984 to 1998. METHODS: Cataract
      extraction information was collected in each biennial questionnaire since 1984. A
      total of 2555 incident breast cancer cases were documented during 14 years of
      followup. The Mantel-Haenszel method and pooled logistic regression with two-year
      time increments were used to estimate the relative risk and 95% confidence
      interval. RESULTS: We found that cataract extraction was not significantly
      associated with increased risk of breast cancer; the relative risks were 1.08
      (95% CI, 0.89-1.31) after controlling for age and 1.06 (95% CI, 0.88-1.29) after
      multivariate adjustment for other risk factors for breast cancer. Also, there
      were no significant differences in the association between cataract extraction
      and risk of breast cancer according to history of diabetes (p for interaction =
      0.11), smoking status (p for interaction = 0.58), and family history of breast
      cancer (p for interaction = 0.22). CONCLUSION: These data suggest that cataract
      extraction is not associated with risk of breast cancer and may not be a good
      indicator of oxidative stress for breast cancer.

PMID- 15456992
TI  - Dietary determinants of circulating insulin-like growth factor (IGF)-I and IGF
      binding proteins 1, -2 and -3 in women in the Netherlands.
AB  - OBJECTIVE: Epidemiological studies suggest that individuals with elevated plasma
      concentrations of insulin-like growth factor (IGF-I) are at increased risk of
      developing cancer. We assessed whether dietary intake of total energy, protein,
      alcohol, phytoestrogens and related foods, and tomatoes and lycopene was
      associated with plasma levels of IGF-I and IGF binding proteins (IGFBPs) in Dutch
      women. METHODS: A cross-sectional study was conducted in 224 premenopausal and
      162 postmenopausal women, aged 49-69, participating in the Prospect-EPIC study in
      the Netherlands. Diet was assessed using a food frequency questionnaire. RESULTS:
      In postmenopausal women, higher alcohol intake was associated with lower plasma
      IGFBP-1 concentrations (alcohol 1.4 to 20 g/day: 20% decrease in IGFBP-1; p =
      0.04), and higher intake of plant lignans was associated with higher IGFBP-1
      concentrations (plant lignans 0 to 1 mg/day: 59% increase in IGFBP-1; p =0.02).
      Higher soy intake was associated with higher plasma IGFBP-2 concentrations in
      premenopausal women (soy 0 to 2.5 g/day: 3% increase in IGFBP-2; p = 0.04). No
      independent associations of dietary factors with IGF-I or IGFBP-3 concentrations
      were observed. However, in premenopausal women alcohol intake was inversely
      associated with IGF-I and positively associated with IGFBP-3 after mutual
      adjustment. CONCLUSIONS: In this study population, with limited variation in
      dietary intake, total energy, protein, phytoestrogens and lycopene were not
      associated with IGF-I and IGFBP-3. Alcohol was inversely, and some measures of
      phytoestrogen intake were positively associated with plasma IGFBP-1 or -2
      concentrations. The roles of IGFBP-1 and -2 in relation to IGF-I bioactivity and
      cancer deserve further investigation.

PMID- 15456993
TI  - Cigarette smoking among lesbians, gays, and bisexuals: how serious a problem?
      (United States).
AB  - INTRODUCTION: Population-based health surveys seldom assess sexual orientation,
      which results in the absence of a reliable measure of smoking among lesbians,
      gays, and bisexuals (LGB), a population perceived to have higher risks of tobacco
      related diseases. This is the first study to compare the cigarette smoking rate
      of LGB with that of heterosexual individuals using a population-based sample with
      both male and female adults, and to identify which sub segments of LGB population
      are particularly burdened by tobacco use. METHODS: California Health Interview
      Survey (CHIS), a population-based telephone survey was used to assess smoking
      prevalence and its correlates among respondents. Of 44,606 respondents, 343 self
      identified as lesbian; 593 self-identified as gay; and 793 identified themselves
      as bisexual (511 female and 282 male). Statistical analysis was performed using
      SAS and SUDAAN. RESULTS: Lesbians' smoking rate (25.3%), was about 70% higher
      than that of heterosexual women (14.9%) Gay men had a smoking prevalence of
      33.2%, comparing to heterosexual men (21.3%). After controlling for demographic
      variables, logistic regression analysis showed that lesbians and bisexual women
      were significantly more likely to smoke compared with heterosexual women (OR =
      1.95 and OR = 2.08, respectively). Gay men were also significantly more likely to
      smoke than heterosexual men (OR = 2.13; 95% CI = 1.66-2.73). Being 35-44-years
      old, non-Hispanic White, and having low-education attainment and low-household
      income were common demographic predictors of cigarette smoking among LGB.
      CONCLUSION: Our study provides the strongest evidence to date that lesbians,
      bisexual females, and gay men had significantly higher cigarette smoking
      prevalence rates than their heterosexual counterparts.

PMID- 15456994
TI  - Phyto-oestrogen intake and breast cancer risk in South Asian women in England:
      findings from a population-based case-control study.
AB  - OBJECTIVE: This study investigates whether intake of phyto-oestrogens is
      associated with breast cancer risk in South Asian women from the Indian
      subcontinent, whose diet is rich in pulses and vegetables but poor in soyfoods.
      METHODS: A total of 240 South Asian breast cancer cases living in England and 477
      age-matched population-based controls were recruited into the study. Dietary
      intake was measured using a validated food frequency questionnaire. Conditional
      logistic regression models were used to estimate the effect of phyto-oestrogen
      intake on breast cancer risk. RESULTS: After adjustment for known breast cancer
      risk factors and total energy intake, there was moderate evidence of a dose
      effect response in the odds of breast cancer with isoflavone intake (p-value for
      trend 0.08), with women in the top quartile having approximately half the odds of
      breast cancer of those in the bottom one (odds ratio (OR) 0.58, 95% confidence
      interval (CI) 0.33, 1.00) but with no reductions in the odds for women in the
      second and third quartiles. The ORs for second, third and highest quartiles of
      total lignan intake compared to the lowest were 0.78 (95% CI 0.48, 1.26), 0.74
      (0.46, 1.19) and 0.66 (0.41, 1.07), respectively, again with moderate evidence of
      a linear dose-effect response (p-value for trend 0.09). Further adjustment for
      non-startch polysaccharides (NSP) intake slightly weakened the phyto-oestrogens
      breast cancer associations. CONCLUSIONS: These findings are consistent with the
      possibility that high phyto-oestrogen intake may protect against breast cancer,
      but further research is required to confirm this hypothesis.

PMID- 15456995
TI  - Prior lung disease and risk of lung cancer in a large prospective study.
AB  - OBJECTIVES: While 75-90% of people who develop lung cancer are smokers, only a
      small proportion of smokers develop lung cancer. Identifying factors that
      increase a smoker's risk of developing lung cancer may help scientists to better
      understand the etiology of lung cancer and more effectively target high-risk
      groups for screening. METHODS: Information on physician-diagnosed non-malignant
      lung diseases [asbestosis, asthma, chronic bronchitis or emphysema (CB/E),
      pneumonia, and tuberculosis] was obtained at baseline from 17,698 men and women
      involved in CARET, a randomized lung cancer prevention trial of beta-carotene and
      vitamin A among heavy smokers and asbestos-exposed workers. Hazard ratios for
      lung cancer were estimated through Cox regression models, after controlling for
      potential confounding factors, included smoking. Analyses were restricted to
      former and current smokers. RESULTS: During a median follow up of 9.1 years, 1028
      cases of lung cancer occurred. Those who developed lung cancer were more likely
      to report a history of CB/E than controls (adjusted HR = 1.29, 95% CI: 1.09
      1.53). In subgroup analyses, the association between a history of CB/E and lung
      cancer was stronger for those who were younger at diagnosis/reference, men in the
      heavy smoker cohort, former smokers, and those with squamous cell carcinomas.
      There was little association between a history of other lung diseases and lung
      cancer. CONCLUSIONS: Smokers with a history of CB/E may be at higher risk of
      developing lung cancer, independent of their smoking history.

PMID- 15456996
TI  - Twinning and the incidence of breast and gynecological cancers (United States).
AB  - Increasing epidemiological and experimental evidence indicates that the
      carcinogenic pathway in the breast and female reproductive organs is driven, at
      least in part, by factors associated with reproduction. We conducted a
      retrospective cohort study, comparing the risk of ovarian, breast, endometrial,
      and cervical cancers among women who had records of at least one twin pregnancy,
      compared with women who had given birth to only single children. Subjects were
      selected from the Utah Population Database, which consists of multiple linked
      datasets including genealogy, births and deaths and cancer registries. We used
      Poisson regression to calculate relative risks, adjusted for the number of
      pregnancies and the age of the mother at the birth of first and last children,
      with singleton mothers as the reference group in each case. The risks of breast
      and ovarian cancers did not differ between mothers of twins and mothers of single
      children. The risk of endometrial cancer was slightly lower in mothers of twins
      than in mothers of singleton children (RR = 0.90, 95% CI 0.67-1.21). Conversely
      the risk of cervical cancer was higher among twin mothers (RR = 1.78, 95% CI 0.88
      3.52). This latter finding supports previous data suggesting that reproductive
      hormones act as cofactors in the etiology of cervical cancer.

PMID- 15456997
TI  - Height and body mass index in relation to esophageal cancer; 23-year follow-up of
      two million Norwegian men and women.
AB  - OBJECTIVE: Associations between body mass index (BMI) and stature and cancers at
      different sites have been explored in a number of studies. For esophageal cancer
      there seems to be different effects of BMI for different histological subtypes.
      We explored these relations in a Norwegian cohort. MATERIAL AND METHODS: Height
      and weight were measured in 2 million Norwegians during 1963-2001. During follow
      up, 2245 histologically verified esophageal cancer cases were registered.
      Relative risks (RR) of esophageal cancer were estimated using proportional Cox
      regression. RESULTS: Compared with normal weighted (BMI 18.5-24.9 kg/m(2)) an
      increased risk of esophageal adenocarcinoma (OA) was observed in overweight men
      (BMI 25-29 kg/m(2)): RR=1.80 (95% CI: 1.48-2.19) and in obese men (BMI > or =30
      kg/m(2)): RR=2.58 (95% CI: 1.81-3.68). The corresponding risk estimates for women
      were RR=1.64 (95% CI: 1.08-2.49) and RR=2.06 (95% CI: 1.25-3.39). The opposite
      relation was observed for esophageal squamous cell carcinoma (OSCC). For
      overweight men the RR of OSCC was 0.72 (95% CI: 0.63-0.82) and 0.68 (95% CI: 0.50
      0.93) for obese. The corresponding RR estimates for women were 0.52 (95% CI: 0.42
      0.65) and 0.43 (95% CI: 0.32-0.59). In addition, the lowest men had the highest
      risk of esophageal cancer in general. Adjustment for smoking did not change these
      relations. CONCLUSION: BMI had opposite relations to the two most common
      histological groups of esophageal cancer. While low BMI increased the risk of
      OSCC, high BMI increased the risk of OA. An increased risk of esophageal cancer
      was found in the lowest men.

PMID- 15456998
TI  - HBV infection and familial aggregation of liver cancer: an analysis of case
      control family study.
AB  - OBJECTIVES: Hepatitis B virus (HBV) infection is one of the most important risk
      factors for hepatocellular carcinoma (HCC). The specific aim of this study is to
      assess the influence of HBV infection on familial aggregation of HCC. METHODS: We
      conducted a population-based case-control family study of liver cancer in
      Taixing, China, in 2001-2002, with a total of 3611 individuals from 202 case
      families and 202 control families. Conditional logistic regression was used for
      the case-control data. The approach of GEE2 was used to analyze the family data
      and age and sex were adjusted in all marginal regression models. RESULTS: The
      odds ratio for HBV associated with HCC was 41.39 (95% confidence interval (CI):
      23.03-74.30). The relatives of cases had a higher risk of liver cancer compared
      with the relatives of controls with a conditional odds-ratio of 3.06 (95% CI:
      1.48-6.33). The association parameters among first- and second-degree relatives
      were no longer statistically significant when HbsAg was taken into consideration.
      CONCLUSION: HBV infection was likely a main reason for the familial aggregation
      of liver cancer in Southern China.

PMID- 15457008
TI  - Breast augmentation.
AB  - The optimal technique for breast augmentation has always been debated, and
      numerous variables fit the needs of the variously shaped patients in our
      population. The purpose of this article is to present the advantages and
      disadvantages of the various techniques available in breast augmentation so that,
      in conjunction with the patient's physical examination, a sound surgical plan can
      be developed for aesthetic augmentation of the breast.

PMID- 15457009
TI  - The beginning of a new era in tissue expansion: self-filling osmotic tissue
      expander--four-year clinical experience.
AB  - The osmotic tissue expander is a new device made of a hydrogel expanding skin
      that does not require external fillings. Once implanted, it absorbs body fluids,
      which leads to a gradual swelling of the device. The swelling phase is completed
      in 6 to 8 weeks and results in skin gain. Different shapes and sizes are
      available, and the devices can be used in almost every area of the body. Over a 4
      year period, the osmotic tissue expander was used in 58 patients in different
      areas of the body. A round osmotic tissue expander was mainly used in breast
      reconstruction, and a rectangular expander was used for defect coverage after
      excision (i.e., of scars and tumors). The mean age of the patients was 49.34
      years (range, 4 to 76 years). During the expansion phase, the patients noted only
      a little discomfort and pain for the first few days. Without a silicone membrane
      in the first-generation expander, the rate of successful explantation and good
      final result was 81.5 percent. In a few cases, rapid swelling of the device led
      to the introduction of a silicone membrane that encloses the expander and leads
      to a slower, more gradual, and consistent swelling. After introduction of the
      silicone envelope, the success rate improved to 91 percent. The expander is now
      used with a silicone membrane in every case. The osmotic tissue expander has many
      advantages compared with the conventional expander: there is no need for painful
      external fillings and the risk of external infections is avoided. The expander is
      10 percent of its final volume and only requires a short incision and a small
      pocket. An operation can easily be performed under local anesthesia, with minimal
      tissue mobilization in older children and compliant patients.

PMID- 15457010
TI  - New technique for correction of the microform cleft lip using vertical
      interdigitation of the orbicularis oris muscle through the intraoral incision.
AB  - A microform cleft lip has three major components: (1) a minor defect of the upper
      vermilion border with loss of the mucocutaneous ridge; (2) a narrow ridge of
      tissue, resembling an exaggerated philtral column extending to the nostril sill;
      and (3) a deformity of the nostril. To attain the muscle continuity without an
      external scar on the upper lip, the author introduced a new method for the
      correction of a microform cleft lip deformity using vertical interdigitation of
      the orbicularis oris muscle through the intraoral incision to create the
      philtrum. Through the intraoral incision, a full-thickness incision is made down
      to the mucosa and the posterior portion of the muscle. Then, the remaining
      portion of the muscle is dissected. The medial and lateral muscle flaps are also
      detached from the oral mucosa and completely exposed and split into two leaves.
      The upper leaf of the lateral muscle flap is sutured to the dermis on the
      philtral dimple and base of the upper leaf of the medial muscle flap. Two leaves
      of each muscle flap are sutured together to create a vertical interdigitation to
      increase the thickness of the philtral column and to provide continuity of the
      muscle. A total of 12 patients with microform cleft lip were treated between
      August of 2001 and October of 2002. Seven of the patients were male and five were
      female, with an age range of 1 to 43 years. The follow-up period ranged from 6
      months to 15 months, with an average follow-up of 9 months. The results of
      vertical interdigitation of the muscle were examined. All patients were satisfied
      with their results. The orbicularis oris muscle provided continuity and preserved
      good function. In all cases, the operation scar was not visible on the depressed
      philtral groove on the cleft side. Correction of cleft lip nasal deformity was
      performed in four patients and alar base advancement was performed in two
      patients. The advantages of the proposed procedure include the creation of an
      anatomically natural philtrum without an external visible scar through the
      intraoral incision, preservation of the continuity and function of the muscle,
      and sufficient augmentation of the philtral column by the vertical
      interdigitation of the muscle.

PMID- 15457011
TI  - Prominent ears in children younger than 4 years of age: what is the appropriate
      timing for otoplasty?
AB  - The present study was conducted to determine whether otoplasty performed in
      children younger than 4 years of age has an acceptable long-term outcome. This
      two-part study consisted of (1) a questionnaire mailed to 481 members of the
      American Association of Plastic Surgeons to ask their opinion on the timing of
      otoplasty, and (2) a consecutive series of 12 patients who had otoplasty
      performed before the age of 4 years. The survey demonstrated that the majority
      (57 percent) of the respondents perform otoplasty on patients who are aged 5
      years or older. The prospective series consisted of 12 patients ranging in age
      from 9 months to 3 years at the time of the procedure. Otoplasty was bilateral in
      nine patients and unilateral in three patients. Length of follow-up ranged from
      21 months to 7(1/2) years, with a median follow-up of 41 months. Growth following
      otoplasty was evaluated in three patients who underwent unilateral otoplasty by
      measuring the length of both ears at the time of final follow-up. No difference
      in ear length was noted between the sides that were and were not operated on
      during a follow-up period of 46 to 63 months. Noticeable recurrence was noted in
      only one (8 percent) of 12 patients. In response to a follow-up questionnaire to
      the patients' families, all respondents (n = 10) stated that if again asked to
      choose the timing of otoplasty in their children, they would opt to have it
      performed at the same age of younger than 4 years. Otoplasty can be safely
      performed at ages younger than previously thought without interfering with growth
      of the operated ear.

PMID- 15457012
TI  - Anatomy of the external nasal nerve.
AB  - After rhinoplasty, many patients report numbness of the nasal tip. This is
      primarily because of injury to the external nasal nerve. It is imperative that
      surgeons performing rhinoplasty be familiar with the anatomy and the common
      variations of this nerve. Therefore, the purpose of this study was to present an
      anatomical study of the external nasal nerve. Twenty external nasal nerves were
      examined by dissecting 10 fresh cadaver noses within 48 hours of death. On
      dissection, the exit of the nerve between the nasal bone and upper lateral
      cartilage was identified. The distance from the point of exit to the midline of
      the nose and the size of the nerve were measured. The course and the running
      plane of the nerve were investigated. The nerve branchings were also classified
      into three types: type I, only one nerve without any branch; type II, one nerve
      proximally and then splitting into two main branches at the intercartilaginous
      junction; and type III, two main branches from the point of exit. The point of
      exit of the external nasal nerve from the distal nasal bone was located 6.5 to
      8.5 mm (7.3 +/- 0.6 mm) lateral to the nasal midline. The average diameter of the
      nerve at the point of exit was 0.35 +/- 0.036 mm. Most of the nerves (95 percent)
      passed through the deep fatty layer directly under the nasal superficial
      musculoaponeurotic layer, all the way down to the alar cartilages. In terms of
      the branching type, type I was observed in 10 of 20 nerves (50 percent), type II
      was observed in six of 20 (30 percent), and type III was seen in four of 20 (20
      percent). On the basis of the results of this study, the following precautions
      are suggested during a rhinoplasty to minimize the chance of injury to this
      nerve. First, it is best to avoid deep intercartilaginous or intracartilaginous
      incisions so that the deep fatty layer is not invaded and the dissection is
      maintained directly on the surface of the cartilage (deep to the nasal
      superficial musculoaponeurotic layer). Second, dissection at the junction of the
      nasal bone and upper lateral cartilage area of one side should be limited to
      within 6.5 mm from the midline. Lastly, when the nasal dorsum is augmented by an
      onlay graft, implants or grafts less than 13 mm wide at the rhinion level should
      be used.

PMID- 15457013
TI  - Quality of life following parotidectomy for malignant and benign disease.
AB  - Parotidectomy is performed for benign or malignant tumors and for selected benign
      inflammatory and autoimmune conditions. Possible associated complications include
      facial nerve paralysis, pain, loss of sensation, gustatory sweating, and facial
      scarring. Global quality of life in patients undergoing parotidectomy has not
      been reported. The implications of facial surgery with the catastrophic potential
      of facial nerve paralysis may severely affect quality of life. A quality-of-life
      study was conducted in patients undergoing parotidectomy for benign and malignant
      diseases to define the significance of associated morbidity and its impact on
      quality of life. A quality-of-life instrument was specifically created, based on
      the principles of the University of Washington Quality of Life questionnaire, and
      mailed to the patients. Questions addressed recognized complications of
      parotidectomy. Patient group results were compared for age above and below 45
      years, sex, benign versus malignant disease, presence or absence of Frey
      syndrome, and presence or absence of benign pleomorphic adenoma. Forty-six
      percent of 125 patients meeting the study criteria fully replied to the
      questionnaire. The global health score was 3.5, corresponding with "good" to
      "very good." Except for local sensation, which had a score of 50, all other
      domains scored above 76. Change in appearance, gustatory sweating, and pain were
      reported by 70 percent, 57 percent, and 30 percent, respectively. Importance
      attributed to all domains except facial function was low. Pain was encountered
      significantly less in patients younger than 45 years of age, and scores for
      appearance were also highly significant in this age group. Postoperative sequelae
      were noted in the majority of patients. The dominant sequelae were altered
      sensation, change in appearance, Frey syndrome, and pain. A degree of permanent
      postoperative facial nerve impairment was reported by 10 patients. Nevertheless,
      overall, parotidectomy does not seem to severely affect quality of life.

PMID- 15457014
TI  - The serratus anterior subslip: anatomy and implications for facial and hand
      reanimation.
AB  - The ideal donor muscle for facial and hand reanimation has yet to be found. Donor
      muscles commonly used today, such as the gracilis and pectoralis minor, are
      limited by bulkiness and the number of force vectors they can provide. In the
      authors' study of 50 fresh cadaver serratus anterior muscles, they further
      describe neurovascular anatomy of the muscle slip (i.e., the portion of the
      muscle that inserts on a rib) and subslip (superficial or deep subdivision of the
      slip after division along a loose areolar plane). All 260 slips could be
      separated into a deep and a superficial subslip, yielding a total of 520
      subslips. A branch of the serratus artery (a terminal branch of the thoracodorsal
      artery serving the lower five to seven slips of the muscle) and a branch of the
      long thoracic nerve were identified for each of these. Deep subslips were thinner
      than superficial subslips, both at the origin of the slip on the rib periosteum
      (2.4 mm versus 3.0 mm, p < 0.0001) and centrally at the serratus artery (3.3 mm
      versus 4.0 mm, p < 0.0001). In addition, the subslips of the most inferior slip
      were thinner than those of more superior slips, both at the origin of the slip
      (2.3 mm versus 2.8 mm, p < 0.0001) and at the serratus artery (3.0 mm versus 3.8
      mm, p < 0.0001). Fine anastomosing vessels were present between the slips and the
      subslips. The average number of anastomosing vessels present between adjacent
      slips was 1.7, and 2.1 anastomosing vessels were present between the subslips of
      a given slip. Given the thinness of these vessels (all less than 0.2 mm) compared
      with those of the vascular pedicle of the subslip (mean, 0.7 mm; all greater than
      0.4 mm), the authors believe these can be safely divided without compromising
      subslip vascularity. After division of these vessels, a mean length of 9.6 +/-
      1.5 cm is available to allow independent orientation of each subslip. When the
      serratus muscle flap is separated into its component subslips, a maximum of 10
      possible force vectors may be transferred on a single vascular pedicle. Subslips
      are significantly thinner than donor muscles commonly used today. These two
      advantages offer the potential for significant functional and aesthetic
      improvement when the serratus anterior muscle flap is used for face and hand
      reanimation. Mimetic muscles such as the orbicularis oculi and orbicularis oris
      could possibly be reconstructed in their proper anatomical positions.

PMID- 15457015
TI  - Breast reconstruction with superficial inferior epigastric artery flaps: a
      prospective comparison with TRAM and DIEP flaps.
AB  - Breast reconstruction using the lower abdominal free superficial inferior
      epigastric artery (SIEA) flap has the potential to virtually eliminate abdominal
      donor-site morbidity because the rectus abdominis fascia and muscle are not
      incised or excised. However, despite its advantages, the free SIEA flap for
      breast reconstruction is rarely used. A prospective study was conducted of the
      reliability and outcomes of the use of SIEA flaps for breast reconstruction
      compared with transverse rectus abdominis musculocutaneous (TRAM) and deep
      inferior epigastric perforator (DIEP) flaps. Breast reconstruction with an SIEA
      flap was attempted in 47 consecutive free autologous tissue breast
      reconstructions between August of 2001 and November of 2002. The average patient
      age was 49 years, and the average body mass index was 27 kg/m. The SIEA flap was
      used in 14 (30 percent) of these breast reconstructions in 12 patients. An SIEA
      flap was not used in the remaining 33 cases because the SIEA was absent or was
      deemed too small. The mean superficial inferior epigastric vessel pedicle length
      was approximately 7 cm. The internal mammary vessels were used as recipients in
      all SIEA flap cases so that the flap could be positioned sufficiently medially on
      the chest wall. The average hospital stay was significantly shorter for patients
      who underwent unilateral breast reconstruction with SIEA flaps than it was for
      those who underwent reconstruction with TRAM or DIEP flaps. Of the 47 free flaps,
      one SIEA flap was lost because of arterial thrombosis. Medium-size and large
      breasts were reconstructed with hemi-lower abdominal SIEA flaps, with aesthetic
      results similar to those obtained with TRAM and DIEP flaps. The free SIEA flap is
      an attractive option for autologous tissue breast reconstruction. Harvest of this
      flap does not injure the anterior rectus fascia or underlying rectus abdominis
      muscle. This can potentially eliminate abdominal donor-site complications such as
      bulge and hernia formation, and decrease weakness, discomfort, and hospital stay
      compared with TRAM and DIEP flaps. The disadvantages of an SIEA flap are a
      smaller pedicle diameter and shorter pedicle length than TRAM and DIEP flaps and
      the absence or inadequacy of an arterial pedicle in most patients. Nevertheless,
      in selected patients, the SIEA flap offers advantages over the TRAM and DIEP
      flaps for breast reconstruction.

PMID- 15457017
TI  - Vacuum-assisted closure: microdeformations of wounds and cell proliferation.
AB  - The mechanism of action of the Vacuum Assisted Closure Therapy (VAC; KCI, San
      Antonio, Texas), a recent novel innovation in the care of wounds, remains
      unknown. In vitro studies have revealed that cells allowed to stretch tend to
      divide and proliferate in the presence of soluble mitogens, whereas retracted
      cells remain quiescent. The authors hypothesize that application of
      micromechanical forces to wounds in vivo can promote wound healing through this
      cell shape-dependent, mechanical control mechanism. The authors created a
      computer model (finite element) of a wound and simulated VAC application. Finite
      element modeling is commonly used to engineer complex systems by breaking them
      down into simple discrete elements. In this model, the authors altered the
      pressure, pore diameter, and pore volume fraction to study the effects of vacuum
      induced material deformations. The authors compared the morphology of deformation
      of this wound model with histologic sections of wounds treated with the VAC. The
      finite element model showed that most elements stretched by VAC application
      experienced deformations of 5 to 20 percent strain, which are similar to in vitro
      strain levels shown to promote cellular proliferation. Importantly, the
      deformation predicted by the model also was similar in morphology to the surface
      undulations observed in histologic cross-sections of the wounds. The authors
      hypothesize that this tissue deformation stretches individual cells, thereby
      promoting proliferation in the wound microenvironment. The application of
      micromechanical forces may be a useful method with which to stimulate wound
      healing through promotion of cell division, angiogenesis, and local elaboration
      of growth factors. Finite element modeling of the VAC device is consistent with
      this mechanism of action.

PMID- 15457019
TI  - Application of the cross-bridge microvascular anastomosis when no recipient
      vessels are available for anastomosis: 85 cases.
AB  - The purpose of this article is to introduce the results of free tissue transfers
      using the technique of the cross-bridge microvascular anastomosis when the
      recipient lacks suitable vessels for anastomosis. Between May of 1982 and June of
      2002, a series of 85 patients underwent this procedure. The transferred tissues
      were the free latissimus dorsi myocutaneous flap, the free vascularized fibula,
      the free fibular osteocutaneous flap, and the free iliac osteocutaneous flap,
      alone or in combination. The donor vessels were the anterior tibial artery and
      great saphenous vein, the posterior tibial artery and its venae comitantes, and
      the radial artery and cephalic vein. Good results were achieved. The success rate
      reached 95.29 percent. The authors believe this procedure can be performed in the
      event of serious tissue defect where the vessels are unsuitable for anastomosis.

PMID- 15457020
TI  - Vascular anatomy of the anterolateral thigh flap.
AB  - Arterial and venous anatomy and their relation to the anterolateral thigh flap
      were examined in 10 specimens of six fresh cadavers in which radiopaque materials
      were injected into both the arterial and venous systems. Territories and
      positions of individual perforating arteries were measured, and the venous
      drainage pathway of the flap was analyzed. All specimens were radiographed
      stereoscopically to observe the three-dimensional structure of the arteries and
      veins. The territory of each perforating artery was smaller than expected. Most
      of the venous blood that had perfused the dermis was considered to pool in a
      polygonal venous network located in the skin layer and to enter the descending
      branch of the lateral circumflex femoral artery through large descending veins.
      The venous territories were considered different from the arterial territories.
      The findings in this study suggest that the design of the anterolateral thigh
      flap should be based on the venous architecture rather than on the arterial
      architecture and that the flap survival rate might be improved if thinning is
      performed appropriately.

PMID- 15457021
TI  - The descending branch of the superficial circumflex artery supplying anteromedial
      thigh skin.
AB  - This report presents an extended groin flap design that consists of a
      conventional skin paddle in the groin region and a vertical extension in the
      anteromedial thigh region, based on the superficial iliac circumflex artery and
      an unnamed descending branch, respectively. The inferior branch of the
      superficial iliac circumflex artery that supplies the thigh extension of the
      flap, spanning approximately the upper half of the thigh region, was found to
      originate approximately 2 cm from the origin of the superficial iliac circumflex
      artery. A total of six free and four local flaps were used in 10 patients with
      ages ranging from 10 to 60 years (average, 45 years). There were six male and
      four female patients. The free flaps were required for total facial resurfacing,
      through-and-through cheek defect, and burn scar contractures and traumatic
      defects of the lower extremity. The local flaps were used for reconstruction of
      scrotum defect, trochanteric decubitus ulcer, and lower abdominal skin and fascia
      defects. All 10 flaps survived completely. The groin flap with anteromedial thigh
      extension offers the following advantages: (1) it is very easy and quick to
      elevate; (2) a significantly increased volume of tissue is available for
      reconstruction, based on one axial vessel and being completely reliable; (3) the
      flap offers two skin paddles that are independently mobile; (4) there is no need
      for positional change and a two-team approach is possible; and (5) it can be
      raised as a vertical skin island only. The authors conclude that the groin flap
      with anteromedial thigh extension is a useful modification for reconstruction of
      both distant and local defects.

PMID- 15457022
TI  - Lower extremity muscle perforator flaps for lower extremity reconstruction.
AB  - A true muscle perforator flap is distinguished by the requisite intramuscular
      dissection of its musculocutaneous perforator to capture the same
      musculocutaneous territory but with total exclusion of the muscle, and thereby
      results in minimal functional impairment. Adhering to this definition, several
      lower extremity donor sites now are available, each with specific attributes
      especially useful for consideration in the treatment of lower extremity defects.
      In this author's experience over the past two decades, 20 lower extremity muscle
      perforator flaps using multiple donor sites proved advantageous for lower
      extremity coverage problems as either a local pedicled flap or as a microsurgical
      tissue transfer. Significant complications occurred in 30 percent of flaps (six
      of 20) in that further intervention was required. Venous insufficiency and
      bulkiness were found to be the major inherent shortcomings. However, giant flaps,
      lengthy and large-caliber vascular pedicles, and the possibility for combined
      flaps were important assets. The choice of a lower extremity muscle perforator
      flap for lower extremity reconstruction limited the surgical intervention and
      morbidity to a single body region.

PMID- 15457023
TI  - Comparison of transthecal digital block and traditional digital block for
      anesthesia of the finger.
AB  - A randomized, double-blind study was performed in 50 patients to compare the
      transthecal and traditional subcutaneous infiltration techniques of digital block
      anesthesia regarding the onset of time to achieve anesthesia and pain during the
      infiltration. All the patients had sustained injury involving two or four fingers
      of the hand. Each patient served as his or her own control, having one finger
      infiltrated with the transthecal technique and the other with the subcutaneous
      infiltration technique. Time to loss of pinprick sensation and pain (at the time
      of the infiltration and 24 hours postoperatively) were assessed using a visual
      analogue scale and verbal response score. A total of 104 blocks (52 transthecal
      and 52 subcutaneous infiltration) were performed. All of these blocks were
      successful. Mean time to achieve anesthesia with the transthecal block was 165
      seconds, compared with 100 seconds for the subcutaneous infiltration block. The
      mean analogue pain score was higher for transthecal blocks than for subcutaneous
      infiltration blocks (3.2 +/- 0.19 versus 1.6 +/- 0.14). Twenty-four hours
      postoperatively, 24 patients who had the transthecal block experienced pain at
      the injection site of the digit. However, none of the patients who received the
      subcutaneous infiltration block complained of pain at the digit. The technique of
      anesthesia preferred by patients for their finger was the subcutaneous
      infiltration block, because it causes less pain. Our results confirm the efficacy
      of the transthecal block for achieving anesthesia of the finger; however, because
      it is a more painful procedure, it is not recommended.

PMID- 15457025
TI  - A meta-analysis of randomized controlled trials comparing endoscopic and open
      carpal tunnel decompression.
AB  - Controversy exists regarding the benefit of endoscopic carpal tunnel release
      versus open carpal tunnel release in terms of grip/pinch strength, scar
      tenderness, pain, return to work, reversible/irreversible nerve damage, and
      adverse effects. Although a number of randomized controlled trials and systematic
      reviews have been published on the subject, to date, no large definitive
      randomized controlled trial or meta-analysis has been performed comparing
      endoscopic to open carpal tunnel release. This meta-analysis was undertaken to
      address the effectiveness of endoscopic carpal tunnel release relative to open
      carpal tunnel release. Key outcome measures from 13 randomized controlled trials
      were extracted and statistically combined. Heterogeneity was observed in three of
      the outcomes (i.e., grip strength, pain, and return to work), but the causes of
      heterogeneity could not be explained because of insufficient detail in the
      reported studies. Using the Jadad et al. scale, nine of 13 studies were of low
      methodologic quality. The effect sizes were compared between the studies that
      were rated as high quality and the studies that were rated as low quality on the
      Jadad et al. scale. Similarly, the studies that were rated as high quality on the
      Gerritsen et al. scale were compared with those that were rated as low quality.
      No clinically significant difference in effect sizes was apparent between studies
      of high and low methodologic quality. This meta-analysis supports the conclusion
      that endoscopic carpal tunnel release is favored over the open carpal tunnel
      release in terms of a reduction in scar tenderness and increase in grip and pinch
      strength at a 12-week follow-up. With regard to symptom relief and return to
      work, the data are inconclusive. Irreversible nerve damage is uncommon in either
      technique; however, there is an increased susceptibility to reversible nerve
      injury that is three times as likely to occur with endoscopic carpal tunnel
      release than with open carpal tunnel release.

PMID- 15457026
TI  - Analysis of publications in three plastic surgery journals for the year 2002.
AB  - The goal of this study was to analyze the publications in the plastic surgery
      literature for the year 2002. Contents of these articles, authors' information
      (such as nationality affiliation of the first author), type of institution,
      presence of grant support, and previous presentation were analyzed. For inclusion
      in this study, the publications had to be original articles from the three most
      frequently read general plastic surgery journals: Annals of Plastic Surgery,
      British Journal of Plastic Surgery, and Plastic and Reconstructive Surgery. With
      this approach, 533 articles were included in the study. To give a cross-sectional
      analysis of the content of all articles, 11 distinct categories were created in
      which all the articles were subsummarized. The categories were based on
      anatomical regions and specific plastic surgical areas. A summary is given for
      each of the categories to provide an overview of the field in which most of the
      research in plastic surgery was taking place in 2002 and which topics were
      focused on. The authors found that only 7 percent of all articles had grant
      support, whereas 36 percent of articles were presented previously during a
      scientific meeting. Most of the articles came from university-based institutions
      (68 percent), followed by non-university-based institutions (29 percent) and
      private practice (3 percent). Regarding nationality affiliation, most of the
      articles came from the United States (n = 229) and Europe (n = 128); in Asia,
      Turkey (n = 39) and Japan (n = 36) were the countries with the most published
      articles.

PMID- 15457027
TI  - A 1-year study of osteoinduction in hydroxyapatite-derived biomaterials in an
      adult sheep model: part II. Bioengineering implants to optimize bone replacement
      in reconstruction of cranial defects.
AB  - The present study investigated hydroxyapatite biomaterials implanted in critical
      size defects in the calvaria of adult sheep to determine the optimal
      bioengineering of hydroxyapatite composites to facilitate bone ingrowth into
      these materials. Five calvarial defects measuring 16.8 mm in diameter were made
      in each of 10 adult sheep. Three defects were filled with cement paste composites
      of hydroxyapatite and beta-tricalcium phosphate as follows: (1) 100 percent
      hydroxyapatite-cement paste, (2) 60 percent hydroxyapatite-cement paste, and (3)
      20 percent hydroxyapatite-cement paste. One defect was filled with a ceramic
      composite containing 60 percent hydroxyapatite-ceramic, and the fifth defect
      remained unfilled. One year after implantation, the volume of all biomaterials
      was determined by computed tomography, and porosity and bone replacement were
      determined using backscatter electron microscopy. Computed tomography-based
      volumetric assessment 1 year after implantation demonstrated that none of the
      unfilled cranial defects closed over the 1-year period, confirming that these
      were critical-size defects. There was a significant increase in volume in both
      the cement paste and ceramic implants containing 60 percent hydroxyapatite (p <
      0.01). There was no significant change in volume of the remaining cement paste
      biomaterials. Analysis of specimens by backscatter electron microscopy
      demonstrated mean bone replacement of 4.8 +/- 1.4 percent (mean +/- SEM) in 100
      percent hydroxyapatite-cement paste, 11.2 +/- 2.3 percent in 60 percent
      hydroxyapatite-cement paste, and 28.5 +/- 4.5 percent in 20 percent
      hydroxyapatite-cement paste. There was an inverse correlation between the
      concentration of hydroxyapatite and the amount of bone replacement in the cement
      paste for each composite tested (p < 0.01). Bone replacement in 60 percent
      hydroxyapatite-ceramic composite (13.6 +/- 2.0 percent) was not significantly
      different from that in 60 percent hydroxyapatite-cement paste. Of note is that
      the ceramic composite contained macropores (200 to 300 microm) that did not
      change in size over the 1-year period. All cement paste composites initially
      contained micropores (3 to 5 nm), which remained unchanged in 100 percent
      hydroxyapatite-cement paste. Cement paste implants containing increased
      tricalcium phosphate demonstrated a corresponding increase in macropores
      following resorption of the tricalcium phosphate component. Bone replacement
      occurred within the macropores of these implants. In conclusion, there was no
      significant bone ingrowth into pure hydroxyapatite-cement paste (Bone Source,
      Stryker-Leibinger Inc., Dallas, Texas) in the present study. The introduction of
      macropores in a biomaterial can optimize bone ingrowth for reconstruction of
      critical-size defects in calvaria. This was demonstrated in both the ceramic
      composite of hydroxyapatite tested and the cement paste composites of
      hydroxyapatite by increasing the composition of a rapidly resorbing component
      such as beta-tricalcium phosphate.

PMID- 15457029
TI  - Accelerating tissue expansion by application of topical papaverine cream.
AB  - The rate of tissue expansion can be accelerated by papaverine through a special
      delivery system, according to an early report. Because the delivery system was
      complex and inconvenient, another means of administrating papaverine was tested
      to observe the rate of tissue expansion. In this study, 24 miniature pigs were
      divided equally into three groups. Four 150-ml silicone expanders were implanted
      into each pig in groups A and C. Four modified rectangular silicone expanders
      were also implanted into each animal in group B. During the expansion process, 1
      g of 2% hydrochloride papaverine cream was applied topically onto the surface of
      each pig's expanding skin in group A two times daily, and hydrochloride
      papaverine solution was injected into the outer shell of each modified expander
      in group B weekly. Group C acted as the control group. The mean sum of the first
      four times of saline water volume that was injected into the expanders was 142.42
      +/- 5.6 ml in group A, 128.72+/-4.8 ml in group B, and 106.38+/-3.28 in group C.
      There were statistical differences among the three groups. The mean sum of volume
      saline water that was injected into hind expanders was 137.51 +/- 5.1 ml in group
      A, 120.35 +/- 3.6 ml in group B, and 102.63 +/- 4.76 ml in group C, and there was
      a statistical difference among the three groups as well. There was no
      statistically significant difference in the thickness of fibrous capsules among
      the three groups. This study shows that the rate of tissue expansion can be
      accelerated by topical application of papaverine cream, and the rate is better
      than the rate of tissue expansion induced by the special drug delivery system.

PMID- 15457030
TI  - Fungal growth inside saline-filled implants and the role of injection ports in
      fungal translocation: in vitro study.
AB  - Infection is a serious complication of breast augmentation and tissue expansion
      with inflatable devices. Several reports have shown that fungi may be able to
      survive, colonize, and even cause infection in saline-filled devices. The
      mechanism of how they penetrate, spread, and colonize inside the inflatable
      implants is not exactly understood. The authors assessed both the expander
      membrane and the port in terms of leakage and penetration of Candida albicans and
      Aspergillus niger in an in vitro model. Thirty saline-filled expanders connected
      to the injection port were placed in sterile containers filled with tryptic soy
      broth culture medium to simulate the clinical situation in phases I and II.
      Intact and multipunctured ports were used in the first and second phases of the
      study, respectively. Either the container or the implant was inoculated with one
      of these fungi, and six implants in containers without fungal inoculation served
      as controls. As a third phase, intraluminal survival of fungi was investigated in
      saline-filled containers (n = 12) in 21 days. The silicone membrane, with its
      intact connecting tube and port, was impermeable to these fungi, whereas both
      fungi were able to diffuse inside-out or outside-in through the punctured ports.
      C. albicans did not survive beyond 18 days in saline, whereas A. niger continued
      to multiply at day 21. Chemical analyses of the implant fluids revealed that the
      contents of the culture medium diffused into the implants in phases I and II. The
      data show that an intact silicone membrane is impermeable to fungi, and punctured
      ports allow translocation of fungi into the implants. Fungi can grow and
      reproduce in a saline-only environment, and their survival periods differ among
      the species. Furthermore, their survival may be enhanced by the influx of
      substances through the implant shell.

PMID- 15457031
TI  - Comparison of TRAM and DIEP flap physiology in a rat model.
AB  - Dynamic and physiologic studies objectively comparing the attributes of the
      transverse rectus abdominis musculocutaneous (TRAM) and deep inferior epigastric
      perforator (DIEP) flaps would be most practical in an animal model. This has now
      been accomplished using the ventral abdomen of the Sprague-Dawley rat. A
      conventional TRAM flap, a multiple perforator DIEP flap, and a solitary
      perforator DIEP flap were raised in three equal groups of five rats each. Flow
      studies using laser Doppler flowmetry demonstrated the highest flow in zone I in
      the TRAM flap group (87.6 +/- 15.4 percent), which was a statistically
      significant difference from the multiple perforator DIEP flap group (45.4 +/-
      13.3 percent) and the solitary perforator DIEP flap group (43.4 +/- 26.4 percent)
      (p = 0.005). Flow in zone IV was proportionately lower for all groups, with no
      significant difference noted between TRAM and DIEP flaps (p = 0.736). Although
      ultimate flap survival was greatest for the TRAM flap group (96.1 +/- 6.7
      percent) when compared with the multiple perforator DIEP flap (79.8 +/- 15.2
      percent) or the solitary perforator DIEP flap groups (77.1 +/- 23.0 percent),
      this difference was not statistically significant (p = 0.183). In summary,
      relative flow to these rat ventral abdomen models was directly proportional to
      the number of retained musculocutaneous perforators, but a single perforator only
      could routinely allow near-total survival.

PMID- 15457032
TI  - Pulsed magnetic fields applied to a transferred arterial loop support the rat
      groin composite flap.
AB  - Pulsed magnetic fields have been shown to stimulate neovascularization in the
      authors' laboratory. The rat groin composite flap was used to create a
      prospective randomized trial to test the effectiveness of these pulsed magnetic
      fields. The skin paddle to this flap is highly consistent, and the authors
      proposed using the flap to study how pulsed magnetic fields affect composite flap
      survival when the dominant vessel to the flap is divided and flap survival
      becomes dependent on a transferred vessel loop. Forty-three rats had the tail
      artery microsurgically anastomosed to the femoral artery and placed between the
      groin musculature and the abdominal skin. Pulsed magnetic energy of 1 gauss was
      applied for 8 (n = 14) or 12 (n = 8) weeks to the experimental groups. Control
      groups were treated in a comparable manner for 8 (n = 16) or 12 (n = 5) weeks.
      After the 8 or 12 weeks, all groups had an 8 x 4-cm skin flap raised, and the
      superficial epigastric artery, the main feeding vessel, was ligated. After 5
      days, the total area of the flap and the area of necrosis were traced onto velum
      paper for each rat. The percent survival was calculated per rat, and a mean
      survival percentage was calculated per group. The experimental animals treated
      with pulsed magnetic fields for 8 weeks had statistically significant improved
      flap survival over the control animals. The study provides evidence that pulsed
      magnetic energy stimulates angiogenesis and suggests a possible use of this
      modality to create island vascular flaps in otherwise random vascular
      territories.

PMID- 15457033
TI  - Island rat groin flaps with twisted pedicles.
AB  - Clinical attempts are made to avoid rotating a flap and twisting the pedicle for
      fear of perfusion compromise. Torsion of an island rat groin flap pedicle is not
      a well-recognized experimental entity. The authors describe the results of island
      flap rotation with pedicle twisting in the rat groin flap model. Forty male
      Wistar rats were randomly divided into four groups of 10 animals each. In each
      group, bilateral groin flaps were elevated; one flap was sutured in place without
      rotation and the contralateral flap was subjected to 180, 270, 360, or 720
      degrees of rotation. Blood flow within the flaps was assessed by laser Doppler
      flowmetry, and flap edema and necrosis were determined 10 days postoperatively.
      No differences were noted between control flaps and those subjected to 180 and
      270 degrees of rotation. Although flaps subjected to 360 degrees of rotation
      demonstrated a large amount of postoperative edema and congestion of the
      subcutaneous tissue with some histologic changes, all flaps in this group
      survived. Measured flap weights at death were different from those of controls.
      All flaps subjected to 720 degrees of rotation underwent ischemic necrosis.
      Because of the differences between human skin architecture and rat skin
      architecture it cannot be concluded that similar results would be observed in any
      human skin flap. There might be three important points arising from this study of
      unknowingly twisted island groin flap pedicles in the rat model: (1) twisting of
      less than 360 degrees has no effect on flap survival; (2) twisting of 720 degrees
      is always associated with skin flap necrosis; (3) twisting of 360 degrees,
      although associated with some changes, does not cause skin flap necrosis.

PMID- 15457034
TI  - A mixed heterotopic gastrointestinal and respiratory cyst of the oral cavity with
      an intraosseous component.

PMID- 15457035
TI  - Simultaneous reconstruction of the breast and empyema defect using a delayed TRAM
      flap and tissue expansion.

PMID- 15457036
TI  - Primary skin grafting in ear lobule keloid.

PMID- 15457037
TI  - Functional biceps brachii reconstruction using the free tensor fasciae latae.

PMID- 15457038
TI  - Graft site malignancy following treatment of full-thickness burn with cultured
      epidermal autograft.

PMID- 15457039
TI  - The free "mutton chop" flap: a fascio-musculocutaneous flap for the
      reconstruction of the entire sacral and perineal area.

PMID- 15457040
TI  - Technical refinement in the management of circumferentially avulsed skin of the
      leg.

PMID- 15457041
TI  - Update on replantation of degloved skin of the hand.

PMID- 15457042
TI  - On the emerging evidence of a new category of duplication in the human hand: the
      dorsoventral duplication.

PMID- 15457043
TI  - Frank Hastings Hamilton: a pioneer American plastic surgeon.

PMID- 15457044
TI  - A walk through Franklin's Philadelphia: then and now.

PMID- 15457045
TI  - Decision and management algorithms to address patient and food and drug
      administration concerns regarding breast augmentation and implants.
AB  - During the U.S. Food and Drug Administration's advisory panel hearings to
      evaluate the premarket approval for conventional silicone gel implants on October
      14 and 15, 2003, panel members and patient advocate representatives focused on
      four specific areas of concern: reoperation rates in primary breast augmentation;
      levels, depth, and methods of patient education and informed consent; modes,
      frequency, and management of silicone gel implant device failures, including
      management of "silent" ruptures; and methods of monitoring and managing symptoms
      or symptom complexes that may or may not be associated with connective tissue
      disease or other undefined symptom complexes. These concerns, with a reported 20
      percent reoperation rate for primary augmentation within just 3 years, and a lack
      of concise, definitive management protocols addressing these areas of concern may
      have contributed to the Food and Drug Administration's rejection of the premarket
      approval, despite the panel's recommendation for approval. This article presents
      decision and management algorithms that have been used successfully for 7 years
      in a busy breast augmentation practice (Tebbetts and Tebbetts). The algorithms
      have been further expanded and refined by a group of surgeons with diverse
      experiences and expertise to address the following clinical situations that
      coincide with concerns expressed by patients and the Food and Drug
      Administration: implant size exchange, grade III to IV capsular contracture,
      infection, stretch deformities (implant bottoming or displacement), silent
      rupture of gel implants, and undefined symptom complexes (connective tissue
      disease or other). In one practice (Tebbetts and Tebbetts) that uses the TEPID
      system (tissue characteristics of the envelope, parenchyma, and implant and the
      dimensions and fill distribution dynamics of the implant), implant selection is
      based on quantified patient tissue characteristics, pocket selection is based on
      quantified soft-tissue coverage, and anatomic saline implants have fill volumes
      that are designed to minimize shell collapse and fold fatigue; in this practice,
      the algorithms contributed to a 3 percent overall reoperation rate in 1662
      reported cases with up to 7 years of follow-up, compared with a 20 percent
      reoperation rate at 3 years in the 2003 premarket approval study.

PMID- 15457046
TI  - "Out points" criteria for breast implant removal without replacement and criteria
      to minimize reoperations following breast augmentation.
AB  - Breast augmentation is a totally elective, medically unnecessary procedure, and
      surgeons and patients must prioritize minimizing tradeoffs, costs, and risks at
      the primary operation and at reoperations. At the U.S. Food and Drug
      Administration's advisory panel hearings in October of 2003 to consider approval
      of conventional silicone gel implants, data documented an overall reoperation
      rate of 20 percent at just 3 years after primary breast augmentation.
      Subsequently, the premarket approval was not granted. Similarly high reoperation
      rates have been reported in previous saline and silicone gel premarket approval
      studies over the past two decades, demonstrating that high reoperation rates are
      not device dependent and suggesting a need to reexamine surgical management
      criteria. Bilateral implant removal without replacement limits additional
      reoperations in a wide range of clinical situations. Surgeons and patients often
      prefer other options to avoid removal without replacement, but other options
      carry a higher tradeoffs, costs, and risks to the patient. If minimizing
      tradeoffs, costs, and risks of reoperations is a priority, surgeons must define
      and patients must understand and accept "out points," that is, specific criteria
      for bilateral implant removal without replacement. Defining out points is
      challenging. Enforcing them when difficult clinical situations occur is even more
      challenging. This article presents out points that have been incorporated into
      staged, repetitive informed consent documents and used in the author's practice
      for more than 10 years. In peer-reviewed and published reports of more than 1600
      patients, these out points criteria, in conjunction with the TEPID system (tissue
      characteristics of the envelope, parenchyma, and implant and the dimensions and
      fill distribution dynamics of the implant) of implant and pocket selection based
      on individual patient quantifiable tissue criteria and surgical techniques that
      minimize tissue trauma and bleeding, resulted in an overall reoperation rate of 3
      percent in 1662 reported cases with up to 7 years of follow-up, compared with the
      20 percent reoperation rate at 3 years in the most recent Food and Drug
      Administration study.

PMID- 15457047
TI  - Mandibular angle reduction versus mandible reduction.
AB  - The terms "mandibular angle reduction" and "reduction angleplasty" refer to
      operations to reduce the width of the lower face and change a square face to an
      oval one. Because the terms emphasize the word angle, however, they imply that
      the operations apply to the mandibular angle. The most frequent complaint after
      these operations is that the change in the lateral appearance is clear but that
      the change in the frontal appearance is not noticeable. Such a result is related
      to the fact that bone resection is performed mainly in the mandibular angle area
      and is focused particularly on resection of the posterior projection through
      curved ostectomy. That is, because operations limited to the mandibular angle
      area cannot properly satisfy patients' requirements, the operation must be
      applied to a larger area. Therefore, it seems reasonable to change the terms
      "mandibular angle reduction" and "reduction angleplasty" to "mandible reduction"
      and "reduction mandibuloplasty." In addition, the most important technique in the
      operation is the resection of the outer cortex of the mandible. In particular,
      the corticectomy technique using a reciprocating saw is quite safe and effective
      for the maximum resection of lateral flaring within a very short time.

PMID- 15457048
TI  - Strategies for a successful corrective Asian blepharoplasty after previously
      failed revisions.
AB  - Asian blepharoplasty, although a common procedure, has a relatively high rate of
      complications. Subtle imperfections and more serious iatrogenic complications
      often require immediate attention by the aesthetic surgeon. After attempted
      correction of the deformities, residual problems or new ones can arise.
      Blepharoptosis, supratarsal depression, an excessively high or low crease, a
      short or discontinuous crease, multiple creases, and asymmetric creases are the
      most commonly encountered complications that require special attention in this
      group, which has already undergone more than one surgical procedure. Between
      January of 1996 and December of 2002, 168 Asian blepharoplasty revisions were
      performed by one surgeon (S. H.-T. Chen); of these, 36 patients (21 percent) had
      previously undergone failed revisions. This subgroup of patients consisted of six
      with blepharoptosis, six with asymmetrical eyelid creases, three with supratarsal
      depressions, three with high creases, two with short creases, and 16 with
      combinations of these deformities. The results were graded as excellent, good,
      fair, or poor, based on the symmetry of the eyelids, palpebral fissures, crease
      heights, lengths, shapes, eyelid fullness, and overall aesthetics of the final
      outcome. A survey was performed of patient and surgeon satisfaction and factored
      into the grading system. With an average follow-up period of 16 months (6 to 60
      months), 22 patients (61 percent) were found to have excellent results, 10 (28
      percent) had good results, two (5.6 percent) had fair results, and two (5.6
      percent) had poor results. Corrective procedures after failed revision Asian
      blepharoplasty require special strategic considerations because of the presence
      of extensive scarring and inadequate skin, muscle, and preaponeurotic fat and
      because of the occasional presence of dehiscence of the levator aponeurosis. By
      using careful preoperative evaluation, accurate measurements, precise
      preoperative planning, intraoperative fat repositioning or grafting, skin
      excision or redraping, and proper placement of anchoring sutures, successful
      outcomes can be achieved. The authors evaluate the outcomes and detail the
      surgical procedures that were used to achieve successful outcomes in this
      particularly challenging group of patients.

PMID- 15457050
TI  - Subfascial periareolar augmentation mammaplasty.
AB  - Subfascial placement of implants was introduced 3 years ago. Collected data
      reveal very promising short-term and long-term results in comparison with
      subglandular and subpectoral positioned implants. The clinical experiences of 69
      breast augmentations in the subfascial position are reported. The indications for
      this technique are proposed. The incidence of complications is described from
      clinical experiences and compared with that for other methods. From January of
      1998 through May of 2002, 328 patients underwent periareolar augmentation
      mammaplasty; 105 patients had a subglandular mammaplasty, 154 patients had a
      subpectoral mammaplasty, and from August of 1999 through May of 2002, 69 patients
      had a subfascial augmentation mammaplasty. The mean postoperative follow-up time
      was 3.6 years in the subglandular group, 3.5 years in the subpectoral group, and
      2.9 years in the subfascial group. In comparing the results of the subglandular
      augmentation group with those of the subpectoral and subfascial augmentation
      groups, the total rate of complications diminished significantly. The long-term
      complications of severe capsular contracture, rippling, and nipple sensation and
      numbness in subglandular augmentation mammaplasty could be significantly reduced
      (p < 0.05). The subfascial augmentation mammaplasty unites all the advantages of
      the subpectoral augmentation mammaplasty but eliminates the disadvantages of
      increased postoperative discomfort and disturbing muscle movement of the breast.

PMID- 15457052
TI  - The use of intraoperative grid pattern markings in lipoplasty.
AB  - Intraoperative grid pattern markings have been used in the performance of
      liposuction. Grid pattern markings include series of longitudinal and transverse
      lines to delineate various anatomical boundaries and landmarks, including the
      midline, lateral line, and medial line. The markings are superimposed on the
      customary preoperative markings and divide broad or circumferential body surfaces
      into smaller subunits for liposuction. Grid pattern markings are applied to areas
      such as the anterior thighs, medial thighs, entire abdomen, flanks, back, arms,
      buttocks, calves, and ankles; they are not applied to smaller, less curved areas.
      Eighty-two consecutive patients underwent lipoplasty in 562 areas of the body.
      The revision rate for postliposuction contour irregularities was 4.0 percent
      (nine of 224 areas) where grid pattern markings were used; one area had an
      indentation type of contour irregularity and required autologous fat grafting.
      The revision rate was 1.5 percent (five of 328 areas) where grid pattern markings
      were not used; two areas in one patient had indentation-type contour
      irregularities and required autologous fat grafting. All remaining areas
      requiring revision had protuberant-type contour irregularities and responded to
      additional liposuction only. The use of grid pattern markings is associated with
      a low incidence of serious contour-related complications.

PMID- 15457053
TI  - Component dorsal hump reduction: the importance of maintaining dorsal aesthetic
      lines in rhinoplasty.
AB  - Dorsal hump reduction can create both functional and aesthetic problems if
      performed incorrectly. Component dorsal hump reduction allows a graduated
      approach to the correction of the nasal dorsum by emphasizing the integrity of
      the upper lateral cartilages when performing dorsal reduction. Use of this
      approach can minimize the need for spreader grafts in primary rhinoplasty
      patients. Possible untoward sequelae of dorsal hump reduction include long-term
      dorsal irregularities caused by uneven resection or overresection or
      underresection of the osseocartilaginous hump irregularity; the inverted-V
      deformity; and excessive narrowing of the midvault. The component dorsal hump
      reduction technique is a five-step method: (1) separation of the upper lateral
      cartilages from the septum, (2) incremental reduction of the septum proper, (3)
      dorsal bony reduction, (4) verification by palpation, and (5) final modifications
      (spreader grafts, suturing techniques, osteotomies). A graduated approach is
      described that offers control and precision at each interval. Fundamental to the
      final outcome is the protection and formation of strong dorsal aesthetic lines
      that define the appearance of the dorsum on frontal view. Furthermore,
      preservation of the transverse portions of the upper lateral cartilages is
      essential to maintain patency of the internal nasal valve, maintain the shape of
      the dorsal aesthetic lines, and avoid the inverted-V deformity. Finally, if
      needed, spreader grafts are enormously adaptable and can be customized for any
      deformity (unilateral or bilateral, visible or invisible) to handle functional or
      aesthetic problems.

PMID- 15457056
TI  - Correcting the saddlebag deformity in the massive weight loss patient.
AB  - Skin redundancy of the trunk and thigh is treated by a circumferential
      abdominoplasty and a lower body lift. Despite preservation and tight
      approximation of the subcutaneous facial system, the authors have failed to
      adequately correct severe saddlebag deformity and midthigh laxity in the massive
      weight loss patient. The technique used in the last nine of the senior author's
      43 lower body lifts was modified by fully abducting each operated thigh on a side
      utility table, before closure in the prone position. This maneuver permits an
      increase in width of skin excision and causes the lateral thigh skin to be taut
      upon leg adduction. This is a retrospective review of the senior surgeon's
      experience over a 3-year period. Postoperative follow-up of the nine-patient
      cohort ranged from 8 to 12 months. A standardized set of six-view preoperative
      and postoperative photographs was available for each patient. A regional grading
      system was developed to assign points for deformity seen in preoperative and
      postoperative photographs. To compare the effect of the new technique on the
      correction of hip/lateral thigh deformities, the authors used this same grading
      system to analyze 10 other lower body lift patients treated by the same surgeon
      without full thigh abduction who had six sets of standardized photographs. A
      deformity severity score was determined for each anatomic region by four trained
      observers blinded to the surgical technique. The nonparametric Mann-Whitney U
      test using exact p values was used to compare preoperative and percentage change
      in deformity severity score from preoperative to postoperative scores relative to
      preoperative scores for each anatomical region among subjects in each treatment
      group. The nonparametric Wilcoxon signed rank test using exact p values was used
      to evaluate the change in deformity severity score from preoperative to
      postoperative values. The change in technique resulted in an observable
      symmetrical correction of the severe saddlebag deformity and better contour to
      the distal lateral thighs. All evaluated patients were satisfied with the lateral
      thigh skin contour. The grading system revealed that patients treated with or
      without intraoperative thigh abduction had similar preoperative deformity
      severity scores for each anatomic region (p > 0.05). Postoperatively, all
      subjects showed improvement in scores for all treated regions. However, patients
      closed during full thigh abduction had significantly lower deformity severity
      scores for the hip/thigh complex when compared with patients treated without full
      thigh abduction (p < 0.05). Complications in these 19 patients consisted of one 6
      cm superficial skin layer dehiscence due to a broken polyester suture that healed
      spontaneously. There were three seromas that responded to a short series of
      aspirations or catheter drainage. There were no infections. Distal abdominal flap
      tip skin necrosis in four patients responded to outpatient debridement and healed
      secondarily. A new grading system for body contour deformities was successfully
      utilized to judge differences in the quality of trunk and thigh deformity and
      outcome in 19 patients with adequate photographic records. Tight suture closure
      in full thigh abduction in the prone position results in improved treatment of
      significant saddlebag deformity and midthigh skin laxity in the massive weight
      loss patient. The essential principles are meticulous planning, careful
      isolation, tight closure of the lateral trunk and thigh subcutaneous fascial
      system, and artistic contouring of remaining tissues. Dehiscence, undesirable
      scarring, and seromas were minor issues in the entire group of 43 patients.

PMID- 15457057
TI  - Should I serve on a medical advisory board?

PMID- 15457058
TI  - Different props but the same play.

PMID- 15457059
TI  - Breast-enhancing pills: myth and reality.

PMID- 15457061
TI  - A new method for transnasal canthopexy and fracture fixation.

PMID- 15457062
TI  - Tufted hair folliculitis at a split-skin donor site.

PMID- 15457063
TI  - If a picture paints a thousand words...

PMID- 15457064
TI  - Greater omental autotransplantation in plastic surgery.

PMID- 15457065
TI  - Tougher rules on breast implants in Europe: what will they mean?

PMID- 15457066
TI  - Full-thickness burns following magnetic resonance imaging: a discussion of the
      dangers and safety suggestions.

PMID- 15457067
TI  - Use of a glove as a self-retaining retractor in hand surgery.

PMID- 15457068
TI  - Generation Xers and baby boomers.

PMID- 15457069
TI  - Conserving our future welfare.

PMID- 15457070
TI  - Positive sentinel nodes and melanoma of the head and neck.

PMID- 15457072
TI  - Posterior tibial vein as drainage vessel for the medial plantar flap on the
      lateral plantar artery.

PMID- 15457073
TI  - The tracheostomy hook as a versatile retractor to aid exposure during muscle
      perforator flap dissection.

PMID- 15457074
TI  - Video physiotherapy for hand surgery.

PMID- 15457075
TI  - Three-thousand-year-old written reference to a description of what might be the
      earliest brachial plexus injuries in the Iliad of Homer.

PMID- 15457076
TI  - First dorsal metacarpal artery adipofascial flap for a dorsal defect of the
      thumb.

PMID- 15457077
TI  - A protective, secure alternative in surgical operations brings ease to the
      surgeon: the temporary use of sterile, semielastic, textured gloves.

PMID- 15457078
TI  - Infective costochondritis following breast reconstruction.

PMID- 15457079
TI  - Airway obstruction following closed reduction of nasal fractures.

PMID- 15457081
TI  - An easy and efficient technique to bundle hair in scalp surgery.

PMID- 15457082
TI  - Salicylic acid may be useful in limiting scar formation.

PMID- 15457083
TI  - Near-infrared angiography and prediction of postoperative complications in
      various types of integumentary flaps.

PMID- 15457084
TI  - The European perspective on shorter hours for residents.

PMID- 15457087
TI  - Melanoma - what is new in sentinel node biopsy and locoregional treatments in
      2003? Report of a workshop at the Third Research Meeting on Melanoma, Milan,
      Italy, May 2003.
AB  - This paper reports on the scientific session on sentinel node biopsy, surgery and
      locoregional treatments that took place during the Third Research Meeting on
      Melanoma, Milan, Italy, held in May 2003. It provides an overview of
      contributions presented at the meeting grouped according to subject - ultrasound
      scanning, sentinel node biopsy, mini-invasive surgery and stop-flow limb
      perfusion. The main comments made by the respective rapporteurs are also
      summarized.

PMID- 15457088
TI  - Melanoma heterogeneity: differential, invasive, metastatic properties and
      profiles of cathepsin B, D and L activities in subclones of the B16F10-NEX2 cell
      line.
AB  - Tumour cell lines and in vivo growing tumours are heterogeneous, comprising
      different cell clones. To understand why some cells primarily invade a tissue,
      while others are more apt to metastasize, several clones from the established
      B16F10-Nex2 cell line were isolated and 10 viable cells of each clone were
      injected intravenously into C57Bl/6 and Balb/c mice. Two cell clones (Nex2B and
      Nex2D) showed contrasting metastatic abilities. Clone 2D rather than clone 2B
      colonized the lungs of both mice after intravenous injection. Surprisingly, clone
      2B grew more rapidly than 2D after subcutaneous implantation, significantly
      reducing the survival of injected mice. Clearly, dissociation between
      subcutaneous growth and metastatic ability was observed in clones from the same
      tumour cell lineage. Clone Nex2B continuously released proteolytic activity,
      including cathepsin B, and showed a greater capacity to invade Matrigel than
      clone Nex2D. Clone Nex2D accumulated cathepsins B, D and L intracellularly and
      released a moderate proteolytic activity in vitro that was inhibited with the
      time of incubation. E-64-treated Nex2B cells injected subcutaneously showed a
      significant delay in tumour development and increased survival of challenged
      animals. A similar result was obtained on treatment of clone 2B with chagasin, a
      cysteine proteinase inhibitor from Trypanosoma cruzi, even at 2 microM. Clone
      Nex2D was less sensitive to pretreatment with inhibitors of cysteine proteases
      for tumour development in vivo. Our results suggest that, in a tumour cell
      population, cells dissociate into metastatic and non-metastatic subtypes, and
      that release or accumulation of cathepsins can be a differential trait of these
      cells.

PMID- 15457089
TI  - Effect of glucose stress conditions in BL6T murine melanoma cells.
AB  - Elevated expression of stress proteins can be a characteristic of human cancer
      and may be involved in the development of resistance to some types of
      chemotherapeutic agent. In this paper, the effect of physiological stress
      conditions, such as glucose deprivation, was investigated in overexpressing
      nPKCdelta murine melanoma BL6 (BL6T) cells. Glucose stress conditions decreased
      the proliferative capacity, increasing the percentage of BL6T cells in the G0/G1
      phase of the cell cycle. Furthermore, under such conditions, nPKCdelta, whose
      subcellular localization is cell cycle dependent, showed a cytoplasmic and
      perinuclear localization by immunohistochemistry, this being typical for cells in
      G0/G1 phase. Moreover, these cells expressed GRP-78, a known stress protein. On
      the other hand, glucose depletion enhanced intracellular melanin as well as
      tyrosinase activity and expression. In summary, these data demonstrate that
      stress conditions can modify the biological characteristics of BL6T cells, and
      therefore can select a quiescent cellular population.

PMID- 15457090
TI  - Alkylating benzamides with melanoma cytotoxicity.
AB  - Radioiodinated N-(2-(diethylamino)ethyl)benzamides have recently been discovered
      as selective agents for melanotic melanoma and are used for scintigraphic imaging
      in nuclear medicine. Owing to the high binding capacity, benzamide derivatives
      conjugated with alkylating cytostatics were synthesized and tested for their
      potential for targeted drug delivery. Conjugates of chlorambucil with
      procainamide (1), diethylaminoethylamine (2) and 2-pyrrolidin-1-yl-ethylamine
      (3), as well as 4-(bis(2-chloroethyl)amino)- (6,7) and 4-(N,N-diethyltriazeno)
      substituted (8-10) benzamides, were synthesized. Cell uptake studies with B16
      melanoma cells revealed high uptake of radioiodinated 1 and 2, while
      radiolabelled chlorambucil was found to lack this characteristic. These results
      were confirmed by biodistribution studies in a mouse melanoma model. Viability
      measurements revealed that all chlorambucil-benzamide derivatives showed higher
      toxicity against B16 melanoma and SK-MEL-28 cells than did the parent
      chlorambucil itself, and that the triazene derivatives were more potent than
      dacarbazine, which is currently used as a standard cytostatic drug in melanoma
      therapy. Of all the compounds tested in this series, the triazenes 9 and 10
      showed the most promising targeting effect. The toxicity of these compounds
      against hepatoma cells (MH3924A) and, to a lesser extent, against mouse
      fibroblast (NIH 3T3) and cervix carcinoma (HeLa) cells was also enhanced, but
      they were not as toxic as dacarbazine (HeLa). These findings support the concept
      of a selective, benzamide-mediated in vivo delivery of cytostatics in melanoma
      cells, leading to enhanced efficacy.

PMID- 15457091
TI  - Molecular detection of MART-1, tyrosinase and MIA in peripheral blood, lymph
      nodes and metastatic sites of stage III/IV melanoma patients.
AB  - Melanoma lesions that develop in the same patient at different times or
      simultaneously at different locations may differ antigenically, because malignant
      melanoma is heterogeneous in terms of its biological, immunological and
      metastatic properties. The objective of this study was to characterize the
      molecular profiles of melanoma cells in peripheral blood, lymph nodes and
      metastatic tissues, employing the messenger RNA (mRNA) expression of tyrosinase,
      melanoma-inhibiting activity (MIA) and melanoma antigen recognized by T cells-1
      (MART-1) as markers. Samples of cells propagated from metastatic sites were
      obtained from 17 stage III/IV melanoma patients and assayed by reverse
      transcriptase-polymerase chain reaction (RT-PCR), using specific primers for each
      marker. In eight patients, marker profiles were analysed in simultaneously
      obtained specimens of peripheral blood, lymph nodes and metastatic tissues
      originating from the same patient. Tyrosinase, MIA and MART-1 were expressed in
      59%, 76% and 76% of the metastases, respectively. Simultaneously obtained
      specimens of peripheral blood, lymph nodes and metastatic tissues showed a high
      degree of homogeneity: 60%, 75% and 20% for tyrosinase, MIA and MART-1,
      respectively. Our findings suggest that the rather homogeneous expression pattern
      found in different tumour sites analysed in the same patient is of potential
      prognostic and therapeutic importance. Furthermore, melanoma lesions may be
      negative for the expression of antigens such as MART-1, and discrepancies in
      expression patterns between peripheral blood and metastatic tissues may occur,
      especially for this marker. Finally, our findings support the notion that
      molecular screening using an RT-PCR approach is appropriate in this kind of
      investigation.

PMID- 15457092
TI  - Dermoscopic patterns of cutaneous melanoma metastases.
AB  - Although the long experience acquired with the widespread use of dermoscopy has
      allowed the establishment of criteria for the recognition of benign and malignant
      skin lesions, very few data are available on cutaneous melanoma metastases. As
      the characteristic clinical aspects are multiform and even histological
      evaluation may sometimes be difficult, we have studied and characterized the
      patterns of cutaneous melanoma metastases in dermoscopy. In this paper, we report
      dermoscopic data on 130 histologically confirmed metastases observed in 32
      patients affected by melanoma, with particular emphasis on dermoscopic features.
      Nine dermoscopic elements (homogeneous, saccular, amelanotic, polymorphic and
      vascular patterns, colour, perilesional erythema, pigmentary halo, peripheral
      grey spots) were studied in 130 cutaneous melanoma metastases and compared with
      those of 350 melanomas, 150 common naevi, 40 blue naevi, 40 haemangiomas and 50
      basal cell carcinomas. The saccular and vascular patterns (especially polymorphic
      atypical vessels and winding vessels), as well as pigmentary halo and peripheral
      grey spots, seem to be the most significant elements suggestive of cutaneous
      melanoma metastases. The interest in and importance of the dermoscopic aspects of
      cutaneous melanoma metastases cannot be neglected if the American Joint Committee
      has determined that microsatellitosis and micrometastases are fundamental in the
      new TNM staging classification for cutaneous melanoma.

PMID- 15457093
TI  - Digital surface microscopy analysis of conjunctival pigmented lesions: a
      preliminary study.
AB  - The objective of this study was to investigate whether digital surface microscopy
      (DSM) could be used for the follow-up and comparison of malignant and benign
      conjunctival pigmented lesions (CPLs). Thirty-nine CPLs [16 de novo malignant
      melanomas (MMs), one MM arising from primary acquired melanosis (PAM), six PAMs
      and 16 naevi] were digitally analysed and biopsied. All of the PAMs and 10 naevi,
      which had not been surgically excised, were followed up using DSM. Thirty
      parameters were evaluated grouped into four categories: geometry, colour, texture
      and islands of colour. None of the CPLs that were followed up, which comprised 10
      naevocytic naevi and seven PAMs, showed any morphological change at DSM analysis,
      except for one PAM which developed an MM 1 year later. Of the geometric variables
      examined, the area, maximum diameter and minimum diameter showed significantly
      higher values in MMs compared with benign CPLs. With regard to the colour of
      CPLs, MMs were significantly darker and bluer than naevi. In the texture group,
      contrast was significantly higher in MMs. In the islands-of-colour group, the
      imbalance of blue-grey regions and the presence of dark areas were significantly
      higher in MMs. DSM greatly simplified the follow-up of CPLs, such as PAMs with
      atypia, by providing satisfactory quality images with high reproducibility; this
      technique is also easy to use and well accepted by patients. Moreover, this
      preliminary study allowed us to determine which objective variables could be
      important for distinguishing between benign CPLs and conjunctival MMs.

PMID- 15457094
TI  - Expression of cell adhesion molecules and tumour infiltrating leucocytes in
      conjunctival melanoma.
AB  - AIM: Very little is known about the immunology of conjunctival melanoma. We
      investigated the expression of cell adhesion molecules and the grade of tumour
      infiltration with lymphocytes and macrophages as important members for the
      communication between tumour cells and the immune system. METHODS: Archival
      material from 35 conjunctival melanomas was used for immunohistochemical
      detection of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell
      adhesion molecule-1 (VCAM-1), neural cell adhesion molecule (NCAM), CD3 and CD68
      using monoclonal antibodies. Histological and clinical data for these tumours
      were assessed. RESULTS: ICAM-1 was expressed in 34 of 35 tumours; in 20 cases,
      more than 50% of the cells stained ICAM-1 positive. VCAM-1 was expressed in 21 of
      34 tumours; in 17 cases, only a small proportion (1-25%) stained VCAM-1 positive.
      NCAM was expressed in 14 of 34 tumours; in 11 cases, only a small proportion (1
      25%) stained NCAM positive. CD3-positive leucocytes were found in 26 of 32
      tumours, whereas CD68-positive leucocytes were present in 33 of 34 tumours. Cox
      regression analysis revealed that patients with NCAM-positive tumours had a 6.4
      fold higher risk of dying from conjunctival melanoma (P = 0.02). NCAM-positive
      tumours were preferentially (P = 0.03) located in prognostically 'unfavourable'
      areas (i.e. fornices, palpebral, caruncle) and had no or only a weak CD3-positive
      infiltrate (P = 0.03). CONCLUSIONS: ICAM-1, VCAM-1 and NCAM are differentially
      expressed in conjunctival melanoma. Leucocytes were present in almost every
      tumour. The association between NCAM expression and prognosis may be related to
      the differential anatomical tumour location of NCAM-positive and NCAM-negative
      tumours, and should be considered a preliminary observation due to the limited
      statistical power of this study.

PMID- 15457095
TI  - Ectopic expression of tyrosinase increases melanin synthesis and cell death
      following UVB irradiation in fibroblasts from familial atypical multiple mole and
      melanoma (FAMMM) patients.
AB  - Patients with familial atypical multiple mole and melanoma (FAMMM) [so-called
      familial dysplastic naevus syndrome (FDNS)] have a high risk for the development
      of malignant melanoma. The underlying gene defect has an autosomal dominant
      inheritance with variable expression and incomplete penetrance. Fibroblasts
      derived from FAMMM patients have high sensitivity to UVC and mutagens, e.g. 4
      nitroquinoline-1-oxide. We were interested in identifying how the combination of
      inherent sensitivity to UV light and abnormal melanin synthesis interacts in the
      development of melanoma in FAMMM patients. Intermediates of melanin synthesis
      produce free radicals that are toxic to cells. Atypical moles (dysplastic naevi)
      are engaged in the biosynthesis of abnormal melanin pigments. This study examined
      whether there was any abnormal melanin pigmentation or cell damage after the
      ectopic expression of tyrosinase in fibroblasts from FAMMM patients when compared
      with fibroblasts from normal subjects. Fibroblasts from FAMMM patients (3012T and
      3072T) were associated with a higher sensitivity than normal human fibroblasts to
      the toxicity of UVB. When cells were infected with tyrosinase-expressing
      adenovirus (Ad-HT) and irradiated with UVB, FAMMM fibroblasts showed higher
      tyrosinase activity, produced more melanin pigments and were degraded more
      significantly than normal human fibroblasts. Western blot analysis revealed that
      Ad-HT-infected 3072T produced a larger amount of tyrosinase protein than did Ad
      HT-infected normal fibroblasts after UVB irradiation. Our findings suggest: (1)
      that FAMMM fibroblasts have an unknown machinery which enhances tyrosinase
      expression by UVB irradiation; and (2) that the resulting increase in melanin
      synthesis affects the cytotoxicity of UVB to FAMMM fibroblasts. All of these
      processes may be involved in the genomic instability and development of melanoma
      in FAMMM patients.

PMID- 15457096
TI  - p53 protein expression and TP53 mutations in malignant melanomas of sun-sheltered
      mucosal membranes versus chronically sun-exposed skin.
AB  - In this paper, we compare the expression of the TP53 gene product, p53 protein
      (p53p), in primary malignant melanomas from sun-shielded mucous membranes and
      from chronically sun-exposed skin. Archival tissues from 29 patients with mucosal
      melanomas and from 27 with cutaneous melanomas in facial skin were subjected to
      immunohistochemical procedures using the monoclonal antibody DO-1. p53p
      expression did not differ significantly between the two groups of melanomas. A
      comparison with previously obtained data on TP53 mutations from the same tumours
      showed closer concordance amongst mucosal than amongst skin tumours. Primary
      mucosal melanomas and their satellites showed identical patterns, focal or
      diffuse, of p53p expression. Thus, expression of altered p53p could well
      participate in the clonal expansion of these mucosal melanomas and in tumour
      progression. The p53p characteristics recognized in our investigations are
      amongst the first hallmarks in the emerging molecular pathological profiling of
      mucosal melanomas, and may therefore be useful in exploring the aetiology of UV
      independent melanomas.

PMID- 15457097
TI  - Frequency and characteristics of melanomas missed at a pigmented lesion clinic: a
      registry-based study.
AB  - To ensure the removal of all melanomas at an early phase, a number of benign
      lesions are currently excised for diagnostic evaluation. Nevertheless, little is
      known about the frequency of melanomas missed (neither recognized nor excised for
      diagnostic verification) by early detection practices. This study aimed to
      investigate the diagnostic performance of a specialized pigmented lesion clinic
      (PLC) through linkage with a local cancer registry. In 1997, 1741 individuals
      resident in the area of Florence and Prato, Italy, the catchment area of the
      Tuscany Cancer Registry (RTT), were consecutively examined at a specialized PLC
      that has been running since 1992 at the Department of Dermatology of Florence.
      The outcomes of dermatological consultations retrieved from PLC case notes were
      compared with all the diagnoses of both in situ and invasive melanoma recorded by
      the RTT until 31 December 1999. The performance of the PLC in detecting cutaneous
      melanoma was evaluated in terms of sensitivity, specificity and predictive
      values, with the RTT data as the gold standard. In the population examined at the
      PLC, 15 newly incident melanomas, all histologically demonstrated, were recorded
      by the RTT. In 13 of the 15 cases, excision of the lesion had been recommended by
      PLC staff, while two melanomas, one in situ and one level II 0.60 mm thick
      invasive, were missed and were subsequently excised 586 and 824 days,
      respectively, after the first PLC examination. The clinical and dermoscopic
      features of the invasive lesion were in agreement with a 'featureless' melanoma,
      and lacked the well-established parameters of malignancy. A total of 67 benign
      pigmented skin lesions were excised for diagnostic evaluation. Thus the PLC
      showed a sensitivity in detecting cutaneous melanoma of 86.7% (95% confidence
      interval [CI] 85.1-88.3%), a specificity of 95.4% (95% CI 94.3-96.3%), a positive
      predictive value of 13.7% (95% CI 12.1-15.3%) and a negative predictive value of
      99.9% (95% CI 99.7-100.0%). The ratio of melanomas to benign skin lesions excised
      was 1:5.1. In conclusion, specialized examination of pigmented skin lesions at
      the PLC offered good level of diagnostic performance, with an acceptable cost in
      terms of benign lesions removed and overall a low risk of missing melanomas.

PMID- 15457098
TI  - Transscleral thermotherapy with laser-induced and conductive heating in hamster
      Greene melanoma.
AB  - The purpose of this study was to investigate the cytotoxic effect of heat as
      induced by transscleral thermotherapy (TSTT), which may be of interest in the
      treatment of patients with choroidal melanoma. The aim of TSTT is to heat both
      the sclera and the tumor up to a cytotoxic temperature of about 60 degrees C.
      TSTT was performed in hamsters with subcutaneously implanted Greene melanoma
      covered by a specimen of human donor sclera of thickness 0.5, 0.7 or 0.9 mm. A
      newly developed applicator, which combines conductive episcleral heating at 60
      degrees C with laser-induced heating, was used at laser powers ranging from 500
      to 1500 mW delivered by an 810 nm diode laser, beam diameter 3 mm, and exposure
      time 1 min. Temperatures were measured at the scleral surface and at the sclera
      tumor interface. The extent of tumor necrosis was examined by light microscopy
      and the sclera was examined by polarized light microscopy. Maximal depth of tumor
      necrosis without scleral damage was 4.4 (SD 1.5) mm. The temperature at the
      scleral surface after TSTT was 58.8 (SD 2.4) degrees C. The temperature at the
      sclera-tumor interface ranged from 56.4 (SD 3.7) degrees C at 500 mW to 65.3 (SD
      4.4) degrees C at 1250 mW laser power. Structural changes to the scleral collagen
      started to develop at 1250 mW. TSTT with combined laser-induced and conductive
      heating caused cytotoxic temperatures in the tumor and the sclera, which were
      well tolerated by the scleral collagen.

PMID- 15457099
TI  - The role of taxanes in the treatment of metastatic melanoma.
AB  - The management of patients with metastatic malignant melanoma remains difficult.
      Conventional chemotherapy has been disappointingly ineffective. Dacarbazine
      (DTIC) is considered to be one of the most active single agents with a response
      rate of approximately 15-20%. Many patients who initially respond to treatment
      subsequently relapse. Clearly, there is a need for improvement, and the
      evaluation of new agents is warranted. This article reviews current phase II
      studies of single-agent taxanes and their combinations in patients with
      metastatic melanoma, and examines the likely impact of taxanes on treatment
      strategies. Response rates from phase II trials with single-agent taxanes vary
      from 3.3% to 17%. Prolonged durations of disease control are observed.
      Combinations of taxanes with DTIC, temozolomide, cisplatin, carboplatin and
      tamoxifen have demonstrated response rates from 12% to 41%, suggesting that they
      are at least as effective as various other combination regimens. Encouraging
      results have been produced in the second-line metastatic setting. Taxanes, both
      as single agents and in combinations, may be a treatment option for some patients
      with metastatic melanoma, especially in the second-line setting.

PMID- 15457100
TI  - Cytotoxic effects of violacein in human uveal melanoma cell lines.
AB  - Violacein is the main pigment produced by Chromobacterium violaceum, a
      saprophytic gram-negative bacillus. Violacein is formed by the condensation of
      two modified tryptophan molecules and has potential anti-neoplastic effects. The
      purpose of this pilot study was to investigate the in vitro activity of violacein
      in human uveal melanoma cell lines. Human uveal melanoma cell lines 92.1 and OCM
      1 were incubated with five different concentrations of violacein (10(-5)-10(-9)
      M), and the total cellular protein content was measured by means of the
      sulphorhodamine B assay. Dose-response curves were obtained and the concentration
      inhibiting cell growth by 50% (IC50) together with the concentration inhibiting
      the net cell growth by 50% (GI50) were calculated for both cell lines. Violacein
      IC50 and GI50 concentrations to cell line 92.1 were 2.78 x 10(-6) M and 1.69 x
      10(-6) M, respectively. The IC50 and GI50 concentrations to cell line OCM-1 were
      3.69 x 10(-6) M and 2.12 x 10(-6) M, respectively. Previous studies using the
      same methodology have revealed violacein to have a GI50 in the range (3-6) x 10(
      8) M for MOLT-4 leukaemia, NCI-H460 large cell lung cancer and KM12 colon cancer
      cell lines. Violacein displayed borderline cytotoxic activity in human uveal
      melanoma cell lines 92.1 and OCM-1, as measured by the sulphorhodamine B assay,
      and further studies are necessary to define its suitability as a potential
      therapeutic agent for metastatic uveal melanoma.

PMID- 15457101
TI  - Cure of metastatic melanoma with surgery, low-dose methotrexate and heparin: a
      case report.

PMID- 15457102
TI  - Melanoma metastatic to the gallbladder and small bowel: report of a case and
      review of the literature.
AB  - From post-mortem case records, the small bowel is the most frequent site of
      metastatic melanoma in the gastrointestinal (GI) tract, with gallbladder
      involvement occurring in 15% of cases. However, few cases have been documented in
      living patients and, when found, are associated with a poor prognosis. We report
      a case of a Caucasian man with metastatic gallbladder and small bowel melanoma
      from an unknown primary. He presented with diffuse abdominal pain, vomiting and
      progressive asthenia; subsequently, intestinal obstruction occurred. He had no
      past history of malignant melanoma and the primary lesion was not found. The
      multiple lesions, together with the absence of mucosal involvement in both the
      gallbladder and small bowel, led us to believe that the lesions were metastatic
      deposits from a probably regressed primary melanoma. It should be emphasized that
      surgical resection for melanoma metastatic to the GI tract is recommended for
      palliative reasons and can be performed safely. The clinical presentation,
      diagnosis, treatment and prognosis of previously reported cases of melanoma
      metastatic to the gallbladder and small bowel are reviewed. The differences
      between primary and secondary GI tract melanomas are also discussed.

PMID- 15457103
TI  - Intramedullary spinal cord metastases of melanoma.
AB  - Intramedullary spinal cord metastases (ISCMs) are extremely rare. An exact
      diagnosis may be difficult even when the primary tumour is known. Patients
      usually present with back pain and signs and symptoms of spinal cord compression,
      such as hemiparesis or hemisensory impairments. Magnetic resonance imaging (MRI)
      is considered to be the main diagnostic tool for intramedullary lesions as it is
      very sensitive, but non-specific, in distinguishing between ISCMs and primary
      cord tumours. Optimal treatment in patients with ISCMs remains controversial. We
      report a case of ISCMs of melanoma, with a review of the clinical and
      radiological characteristics of these medullary lesions and their prognosis, as
      well as the different therapeutic approaches.

PMID- 15457104
TI  - Dermatomyositis occurring during treatment of a patient with metastatic melanoma.

PMID- 15457105
TI  - Secondary orbital metastases from cutaneous melanoma.

PMID- 15457106
TI  - Deficits in verbal declarative memory function in women with childhood sexual
      abuse-related posttraumatic stress disorder.
AB  - Several studies have shown deficits in verbal declarative memory function in
      posttraumatic stress disorder (PTSD). Most of these studies have been performed
      in men with combat-related PTSD compared with healthy subjects; relatively little
      is known about memory function in women with abuse-related PTSD, or whether these
      effects are specific to PTSD or are a nonspecific outcome of exposure to early
      abuse. The purpose of this study was to assess declarative memory function in
      women with and without a history of early childhood sexual abuse and PTSD. Forty
      three women with and without a history of early childhood sexual abuse and PTSD
      underwent neuropsychological testing with subtests of the Wechsler Memory Scale-
      Revised for measurement of verbal and visual memory and subtests of the Wechsler
      Adult Intelligence Scale for measurement of IQ, and behavioral ratings of PTSD
      and other psychiatric symptoms. Abused women with PTSD had deficits in verbal
      declarative memory as measured with the subtests of the Wechsler Memory Scale-
      Revised compared with women with early abuse without PTSD and nonabused women
      without PTSD. There were no significant differences in IQ. These findings suggest
      that early abuse with PTSD is associated with deficits in verbal declarative
      memory, and that these effects are not related to the nonspecific effects of
      childhood abuse.

PMID- 15457107
TI  - Depression in young adolescents: investigations using 2 and 3 factor versions of
      the Parental Bonding Instrument.
AB  - Associations between parenting style and depressive symptomatology in a community
      sample of young adolescents (N = 2596) were investigated using self-report
      measures including the Parental Bonding Instrument and the Center for
      Epidemiologic Studies Depression Scale. Specifically, the 25-item 2-factor and 3
      factor models by Parker et al. (1979), Kendler's (1996) 16-item 3-factor model,
      and Parker's (1983) quadrant model for the Parental Bonding Instrument were
      compared. Data analysis included analysis of variance and logistic regression.
      Reanalysis of Parker's original scale indicates that overprotection is composed
      of separate factors: intrusiveness (at the individual level) and restrictiveness
      (in the social context). All models reveal significant independent contributions
      from paternal care, maternal care, and maternal overprotection (2-factor) or
      intrusiveness (3-factor) to moderate and serious depressive symptomatology,
      controlling for sex and family living arrangement. Additive rather than
      multiplicative interactions between care and overprotection were found.
      Regardless of the level of parental care and affection, clinicians should note
      that maternal intrusiveness is strongly associated with adverse psychosocial
      health in young adolescents.

PMID- 15457108
TI  - A ten-year treatment outcome study of traumatized Cambodian refugees.
AB  - The purpose of this study was to assess treatment outcome among 23 severely
      traumatized Cambodian refugee patients with posttraumatic stress disorder who had
      been in continuous treatment for 10 or more years. Primary outcome parameters
      were symptom severity, social and vocational disability, and subjective quality
      of life. All patients were interviewed using standard assessment tools by a
      research psychiatrist not connected with the treatment, and charts were reviewed
      for past and current traumas and for treatment history. There was a wide range of
      current posttraumatic stress disorder symptom scores, but current depression
      scores were very low. Thirteen patients were judged to have good outcomes, and 10
      had relatively poor outcomes. Reported degree of previous trauma and demographic
      factors did not distinguish between the two outcome groups. Sixty percent of
      patients greatly improved. However, even with comprehensive continuous treatment
      over a period of 10 or more years, a substantial minority was still impaired.

PMID- 15457109
TI  - Determinants of postconflict symptoms in Albanian Kosovars.
AB  - During the period from 1998 to 1999, more than 1 million civilians from the
      province of Kosovo in the Balkans were displaced as a consequence of organized
      violence and war. The aim of the present study was to determine the prevalence of
      posttraumatic stress disorder (PTSD) in a sample of the Albanian Kosovar
      population more than 2 years after the end of the conflict and to assess the
      effect of exposure to war-related events. A total of 340 households were randomly
      selected among 12,900 families returned from a country of asylum (Switzerland).
      All adults in each household were invited to participate (N = 996). The following
      instruments were used: the Albanian translations of the PTSD section of the Mini
      International Neuropsychiatric Interview and of the Medical Outcomes Study 36
      Item Short Form, and a list of traumatic events adapted from the Harvard Trauma
      Questionnaire. The overall prevalence of PTSD was 23.5%. A strong cumulative
      effect of trauma was observed, with odds ratios for PTSD rising steeply with the
      number of events to which people were exposed. After taking into account
      traumatic events, multivariable analysis indicated that female gender, older age,
      and having left Kosovo during the conflict were significantly associated with
      higher frequency of PTSD, whereas significant heterogeneity among municipalities
      was observed. Stratified analysis for people who stayed and left the province
      during the war suggested that different patterns of trauma may be relevant in the
      two subsamples, with forced separation and isolation strongly associated with
      PTSD in people who stayed in Kosovo. PTSD diagnosis was also significantly
      associated with lower scores on all dimensions of the Medical Outcomes Study 36
      Item Short Form and lower economic status. The results suggest that responding to
      medium-term and long-term mental health consequences of conflict is a necessary
      task for the global rehabilitation of health care systems in a war devastated
      country.

PMID- 15457110
TI  - Personality characterizations of outpatients with schizophrenia, schizophrenia
      with substance abuse, and primary substance abuse.
AB  - The study extended previous research on the relationship between personality
      traits and Axis I disorders. It examined personality differences between
      individuals diagnosed with schizophrenia and substance abuse and also included
      individuals dually diagnosed with both schizophrenia and substance abuse.
      Comparisons were made with respect to characteristics of both normal personality,
      as measured by the NEO Five-Factor Inventory (NEO-FFI), and disordered
      personality, as measured by the Millon Multiaxial Personality Inventory. On the
      NEO-FFI, all groups differed significantly from the NEO-FFI normative sample on
      at least three personality domains. As predicted, the dual diagnosis group showed
      the most personality deviance and pathology. The schizophrenia group was
      primarily distinguished by higher levels of agreeableness, whereas the substance
      abuse group was more extroverted and showed a prominence of Cluster B personality
      patterns. An unexpected finding was an interaction between diagnostic group and
      age, such that older relative to younger individuals in the single diagnosis
      groups showed greater personality adaptivity and moderation, whereas older
      individuals in the dual diagnosis group showed less.

PMID- 15457111
TI  - Moral conflict, religiosity, and neuroticism in an outpatient sample.
AB  - Our sense of identity is inextricably connected to our sense of ourselves as
      moral beings. However, concerns about the rightness and wrongfulness of our own
      actions, and a range of emotions connected to moral worry, such as regret and
      remorse, rarely receive clinical attention. The present study sought to develop
      and operationalize the construct of moral concern or worry in a psychiatric
      outpatient sample and to investigate relationships between moral worry and age,
      gender, religiosity, and the tendency to worry in general. The Eysenck
      Personality Inventory, Duke Religiosity Scale, and a 20-item Worry Scale
      (containing eight moral worry items) were administered to 225 psychiatric
      outpatients. Data analysis included principal components analysis, repeated
      measures MANOVA to examine extent of worry among factor scales and interactions
      between age and sex, and multiple regression to identify significant correlates
      of each factor scale. Worry about moral issues emerged as a domain distinct from
      worry about practical matters. Although respondents reported more worry about
      practical matters than about moral concerns, worry about the former declined with
      age, whereas worry about the latter did not. Intrinsic religiosity was negatively
      correlated and neuroticism positively correlated with both scales. Because
      patients are concerned about the moral aspects of their character and behavior,
      this area deserves further research and consideration.

PMID- 15457112
TI  - Physiologic evidence for the interpersonal role of laughter during psychotherapy.
AB  - The role of laughter during psychotherapy is poorly understood. This study
      examined 10 unique sessions of psychodynamic psychotherapy with digital videotape
      and simultaneous measures of skin conductivity (SC) from patients and therapists.
      Independent observers coded laugh episodes using published criteria. Observers
      identified 167 laugh responses. Of the 119 patient laughs, 91 (76.5%) were
      patient as speaker, compared with 28 (23.4%) as nonspeaker audience. In contrast,
      of the 48 therapist laughs, only five (10.4%) were therapist as speaker, whereas
      43 (90.3%) were as nonspeaker audience. The difference was highly significant (p
      < .001). Physiologic data showed that mean SC level increased regardless of role
      as patient, therapist, speaker, or audience (p < .001). Two-factor analysis of
      variance indicated that SC change scores were significantly larger when patients
      and therapists laughed together compared with laughing alone (p < .05). The
      results support an empirically based approach to the study of laughter and the
      use of psychophysiology as a measure of process during psychotherapy.

PMID- 15457113
TI  - Internal source monitoring and thought disorder in schizophrenia.
AB  - A new task was developed to examine source monitoring in 52 patients with
      schizophrenia. Patients and nonpsychiatric controls were not found to differ on
      recognition memory, source discrimination, or attribution bias when the between
      group difference in IQ was controlled. However, among patients, source
      discrimination was significantly related to severity of thought disorder. After
      controlling for IQ and verbal working memory, thought-disordered patients were
      significantly poorer than nonthought-disordered patients at discriminating the
      source of previously presented information. Results suggest that internal source
      monitoring is specifically related to thought disorder in patients with
      schizophrenia.

PMID- 15457114
TI  - Psychiatric symptoms and health service utilization in rural and urban combat
      veterans with posttraumatic stress disorder.
AB  - This study investigated differences in rural/urban mental health and service use
      in veterans with combat-related posttraumatic stress disorder (PTSD). Data were
      obtained from 48 urban and 52 rural residing combat veterans diagnosed with PTSD
      at a Veterans Affairs Medical Center's outpatient PTSD clinic. Rural and urban
      groups were compared on health service utilization indices (PTSD, primary and
      specialty care clinic visits), the Minnesota Multiphasic Personality Inventory-2,
      the Mississippi Combat PTSD Scale, the Beck Depression Inventory, and the
      Dissociative Experiences Scale. Results indicated a lack of substantive
      differences between rural and urban combat PTSD patients. The sole difference
      involved higher dissociation scores among rural patients. Rural combat PTSD
      patients therefore seem to have similar mental health needs compared with their
      urban counterparts, with important service delivery implications.

PMID- 15457115
TI  - Prevalence of Veraguth's eyelid folds during depression in different ethnic
      groups.
AB  - A common physical sign associated with depression, Veraguth's eyelid folds, was
      found considerably more often in white than in African American patients with
      depressive illness. Moreover, the folds are more strongly correlated with
      severity of depression in patients of European descent when they occur. The
      reported high rate of misdiagnosis of depressive illness in Americans of African
      descent may thus be related in part to differences in the facial expression of
      affect. The implications of this finding are discussed in regard to the
      importance of careful gathering of history for diagnostic purposes.

PMID- 15457116
TI  - Fuzzy logic detection of medically serious suicide attempt records in major
      psychiatric disorders.
AB  - Clinical prediction of suicide is a complicated task. The focus for improved
      suicide risk detection is on the subgroup of individuals whose high suicide risk
      remains unrecognized by clinicians. We sought to evaluate the accuracy of Fuzzy
      Adaptive Learning Control Network (FALCON) neural networks, a nonlinear
      algorithm, in identification of this subgroup. The study sample included the
      Computerized Scale for risk of Suicide, including 21 suicide risk factors
      (including the target variable) drawn from 987 patient records, completed by
      staff clinicians during face-to-face interviews of hospitalized patients. FALCON
      evaluated all records in two steps: a) 612 for training and 375 for validation,
      and b) 887 for training and 100 for validation. The existence of previous
      medically serious suicide attempts (MSSAs) was chosen as the target variable
      because it is generally recognized as the strongest suicide risk factor.
      Sensitivity, specificity, and unknown answers among MSSA and non-MSSA were as
      follows: 612/375 FALCON, 91%, 85%, 11%, 15%; 887/100 FALCON, 94%, 82%, 20%,
      14.5%, respectively. Trained FALCON, a nonlinear neural network, achieves
      respectable accuracy in detecting MSSA patients based on 20 suicide risk factors.
      Trained FALCON may therefore assist in identification of subgroup of individuals
      who remain unrecognized by clinicians and contribute to prevention of suicide.

PMID- 15457117
TI  - Gambling and suicidality in treatment-seeking pathological gamblers.
AB  - One hundred twenty-five adult participants recruited from gambling treatment
      centers were included in an examination of gambling-related suicidal ideation and
      attempt. In this sample, 48% (N = 60) had a history of gambling-related suicidal
      ideation, and an additional 12% (N = 15) reported at least one gambling-related
      suicide attempt. Measures of gambling experience, impulsiveness, and dissociation
      were evaluated across groups. Level of suicidality was associated with greater
      gambling severity, gambling escape, dissociation and attention seeking,
      impulsivity, and generalized dissociative experience, but not with other
      psychological indices such as empathy or venturesomeness. The implications of
      these findings for the identification and treatment of gamblers at risk for
      suicide are discussed.

PMID- 15457118
TI  - Perceived relationship between military service and homelessness among homeless
      veterans with mental illness.
AB  - This study examined the perceived relationship between military service and the
      risk of homelessness after discharge and identified specific aspects of military
      service that homeless veterans experience as having increased their risk for
      becoming homeless. A cross-sectional survey was conducted among 631 homeless
      veterans enrolled in the VA Therapeutic Employment Placement and Support Program
      from January 2001 through September 2003. Associations of sociodemographic
      characteristics, clinical status, and military service characteristics
      (independent variables) were examined in relation to perceptions of increased
      risk for homelessness and time to first episode of homelessness after leaving the
      military (two dependent variables), using analysis of variance, logistic
      regression, and multiple regression statistical analyses. Fewer than one third
      (31%) of the homeless veterans in this study reported that military service
      increased their risk for homelessness--either somewhat (18%) or very much (13%).
      Among those veterans who perceived military service as increasing their risk for
      becoming homeless, the three aspects of military service most commonly identified
      included a) substance abuse problems that began in the military (75%), b)
      inadequate preparation for civilian employment (68%), and c) loss of a structured
      lifestyle. The relatively small proportion of homeless veterans who attributed
      homelessness to their military service, coupled with the long 14-year average lag
      time between discharge and their first episode of homelessness, is consistent
      with epidemiological data suggesting that military service itself does not
      substantially increase the risk for becoming homeless among veterans.

PMID- 15457119
TI  - Are dreams about drugs, substances, or treatment the royal road to prediction of
      treatment outcome?

PMID- 15457121
TI  - Application of retinoids in the treatment of renal cell carcinoma--a futile
      effort?
AB  - The therapeutic benefit of adding retinoids such as all-trans retinoic acid (RA),
      9-cis-RA or 13-cis-RA to established single-agent or combination
      immuno/chemotherapy regimens for the treatment of metastatic renal cell carcinoma
      (RCC) has been extensively investigated during the last decade. However, at
      present results are contradictory and their application controversial. Moreover,
      recent studies indicated a significantly higher incidence of toxic side-effects
      in patients treated with retinoids in addition to established bio/chemotherapy.
      This Commentary summarizes preclinical and clinical trials investigating efficacy
      and toxicity of retinoids in the treatment of RCC.

PMID- 15457122
TI  - Controlling cancer by restricting arginine availability--arginine-catabolizing
      enzymes as anticancer agents.
AB  - Interest has recently been revived in enzymes that degrade essential amino acids.
      Arginine-catabolizing enzymes now predominate and are discussed in this review.
      Apart from reducing tumor load through cell death occurring as a result of
      deprivation alone, these catabolic enzymes conveniently leave the remaining
      malignant cells vulnerable to other therapeutic modalities through combinatorial
      treatments with cycle-dependent drugs, the timing of additional treatment after
      deprivation being crucial.

PMID- 15457123
TI  - Phase II study of irinotecan (CPT-11) administered every 2 weeks as treatment for
      patients with colorectal cancer resistant to previous treatment with 5
      fluorouracil-based therapies: comparison of two different dose schedules (250 and
      200 mg/m2) according to toxicity prognostic factors.
AB  - Our objective was to assess the antitumoral activity and toxicity of irinotecan
      (CPT-11) 60-min i.v. infusion every 2 weeks as second-line monotherapy of
      advanced colorectal cancer. Two doses were studied (250 and 200 mg/m) according
      to the risk of developing toxicity. Two groups of patients were studied: high
      risk group (HR, 200 mg/m, n = 45; Karnofsky score 60-80% and/or the record of
      prior pelvic irradiation) and low-risk-group (LR, 250 mg/m, n = 51; Karnofsky
      score >80% and without prior pelvic irradiation). The mean number of cycles per
      patient was 7: 6.6 (HR group) and 8.3 (LR group). Median RDI was 0.96. The
      overall response rate was 8.9% [95% confidence interval (CI) 2.5-21.2%; HR group]
      and 15.7% (95% CI 7.0-28.5%; LR group), respectively. The LR group showed two
      complete responses and a higher percentage of stable disease (56.9 versus 33.3%
      in HR group). The median survival was 7.1 months (95% CI 5.2-8.9 months, HR
      group) and 11.7 months (95% CI 8.4-15.1 months, LR group). The median time to
      disease progression was 3.2 months (95% CI 1.0-5.4 months, HR group) and 5.3
      months (95% CI 3.8-6.7 months, LR group). Both CPT-11 treatments were well
      tolerated. Grade 3/4 toxicity incidence was low, e.g. granulocytopenia (7% of
      patients in HR group and 9% in LR group) and delayed diarrhea (18% of patients in
      HR group and 14% in LR group). We conclude that the treatment of patients with
      the adjusted dose of CPT-11 according to prognostic factors for toxicity resulted
      in the improved toxicity profile, but showed poorer efficacy outcome. Therefore,
      the dose reduction in patients with low performance and treated with radiotherapy
      needs further investigation to provide some new insights on the benefit:risk
      ratio of such treatment.

PMID- 15457124
TI  - Effect of combination therapy with aminoglutethimide and hydrocortisone on
      prostate-specific antigen response in metastatic prostate cancer refractory to
      standard endocrine therapy.
AB  - A prospective study was performed to investigate the combination of the aromatase
      inhibitor aminoglutethimide and hydrocortisone in androgen-independent prostate
      cancer with changes in prostate-specific antigen (PSA) level as main determinant
      for response. Thirty-five patients were treated with aminoglutethimide 1000 mg
      daily and hydrocortisone acetate 40 mg daily. PSA measurements were performed
      every month. If evaluable lesions were present, objective tumor assessment was
      done by computed tomography scan and X-ray investigations. In 12 patients (37%)
      the PSA value showed a confirmed response with a decline in serum level of at
      least 50%. Median time to progression in responding and all patients was 10.5 and
      4.5 months, respectively. Median duration of response in responding patients was
      9 months. Median survival for these two groups was 23 and 14.5 months,
      respectively. Of seven patients with measurable disease, two showed a partial
      response and five a stable disease. Improvement in general condition, pain and
      feeling of well-being was noted in two-thirds of patients. Therapy was well
      tolerated with mainly grade I and II adverse events in 20% of patients. We
      conclude that aminoglutethimide is a valuable second-line therapy for patients
      with androgen-independent prostate cancer.

PMID- 15457125
TI  - Ex vivo characterization of XR11576 (MLN576) against ovarian cancer and other
      solid tumors.
AB  - XR11576 (MLN576) is a novel monophenazine with a mechanism of action that
      includes interaction with both topoisomerase (Topo) I and II. The aim of this
      study was to evaluate its cytotoxicity against fresh tumor cells taken from
      patients with a variety of solid tumors. Cells were obtained from 89 patients and
      exposed for 6 days to XR11576 alone, or in combination with doxorubicin,
      cisplatin, treosulfan, paclitaxel or vinorelbine. Cell survival was measured
      using the ATP-Tumor Chemosensitivity Assay (ATP-TCA). Immunohistochemical
      staining of Topo I, Topo IIalpha and MDR1 was performed on paraffin-embedded
      blocks in those tumors for which tissue was available (n = 49). Overall, the
      median IC90 and IC50 values of XR11576 in tumor-derived cells were 242 and 110
      nM, respectively. In all samples XR11576 was more potent than the other
      cytotoxics tested. Breast and gynecological malignancies were most sensitive to
      XR11576, while the potency of this compound was slightly attenuated in
      gastrointestinal tumors, in which the median IC90 and IC50 values were 308 and
      212 nM, respectively. Cases of synergism were identified when combining XR11576
      with vinorelbine (nine of 30 samples) and doxorubicin (12 of 38 samples), while
      the addition of paclitaxel resulted in an antagonistic effect (CI50>1.2) in 38 of
      42 tumors. A very modest correlation by linear regression analysis was found
      between the intensity of MDR1 staining and the IC50 of XR11576 (r = 0.311, p =
      0.0312), but not with the IC90 (r = 0.247, NS). These data support the rapid
      introduction of XR11576 to clinical trials and suggest that it may be effective
      against a broad spectrum of tumor types.

PMID- 15457126
TI  - Ex vivo reversal of chemoresistance by tariquidar (XR9576).
AB  - The expression of P-glycoprotein (P-gp) has been demonstrated to confer
      resistance to several anticancer drugs, including anthracyclines, taxanes and
      vinca alkaloids. Tariquidar is a novel inhibitor of P-gp that has been shown to
      reverse resistance to cytotoxic drugs in tumor cell lines and mouse xenografts.
      We have used an ATP-based chemosensitivity assay (ATP-TCA) to compare the
      activity of cytotoxic drugs in combination with tariquidar against a variety of
      solid tumors (n = 37). The expression of P-gp was determined in a subset of solid
      tumor samples by immunohistochemistry (n = 16). Resistance was seen in 20 of 37
      (54%) tumors tested with doxorubicin, in 27 of 34 (79%) samples tested with
      paclitaxel and 17 of 31 (55%) with vinorelbine. Tariquidar alone showed no
      activity over a wide range of concentrations up to 2 microM (n = 14). The median
      IC90s for doxorubicin, paclitaxel and vinorelbine, alone were 2.57, 27.4 and 15.5
      microM. These decreased to 1.67 (p<0.0005), 20.6 (p<0.05) and 9.5 microM
      (p<0.001), respectively, in combination with tariquidar. Tariquidar also
      significantly decreased resistance in 14 of 20 (70%), six of 27 (22%) and six of
      17 (35%) samples tested with doxorubicin, paclitaxel and vinorelbine,
      respectively. Immunohistochemical staining for P-gp was positive in nine of 16
      (56%) samples and in all of these cases addition of tariquidar improved the
      activity of the cytotoxic. The results show that tariquidar is able to decrease
      resistance in a number of solid tumors resistant to cytotoxic drugs known to be P
      gp substrates. These data support the introduction of tariquidar in combination
      with chemotherapy to clinical trials of patients expressing P-gp.

PMID- 15457127
TI  - Is inhibition of cancer angiogenesis and growth by paclitaxel schedule dependent?
AB  - It has been speculated that weekly paclitaxel enhances antiangiogenesis and,
      hence, results in a greater inhibition of cancer growth than the 3-week schedule.
      We compared the weekly and 3-week schedules of paclitaxel in inhibiting
      angiogenesis, tumor growth and bone marrow hematopoiesis in a lung cancer model.
      Vehicle or paclitaxel was administered i.p. to three groups of nude mice bearing
      a human lung cancer. The vehicle was given weekly for six doses or every 3 weeks
      for two doses (Group A). Paclitaxel was administered at 20 mg/kg/week for six
      doses (Group B) or 60 mg/kg/3 weeks for two doses (Group C). The tumor growth
      rate was reduced by 50% equally in both the paclitaxel-treated groups.
      Intratumoral microvasculature was reduced by 70% in each paclitaxel-treated
      group. However, white blood cell count was significantly reduced in Group C in
      comparison with that of Group A or B. We conclude that in this model,
      angiogenesis and tumor growth were inhibited to the same extent when paclitaxel
      was administered on a weekly or 3-week schedule. Inhibition of tumor growth by
      paclitaxel was associated with suppression of angiogenesis. Weekly administration
      of paclitaxel resulted in a lower degree of leukopenia than with the 3-week
      schedule, mimicking the clinical setting.

PMID- 15457128
TI  - Studies of synergistic and antagonistic combinations of conventional cytotoxic
      agents with the multiple eicosanoid pathway modulator LY 293111.
AB  - The arachidonic acid metabolic pathway is currently under active investigation as
      a promoter of malignancy and several molecules have been synthesized to block
      either the cyclooxygenase or lipoxygenase branches. LY 293111 is an oral agent
      known to be a leukotriene B4 antagonist, a 5-lipoxygenase inhibitor and a
      peroxisome proliferator-activated receptor (PPAR)-gamma agonist with cytotoxic
      properties in cell lines. We have studied this agent with classical
      chemotherapeutic agents in a 72-h culture with cell lines using median-effect
      analysis as a measure of antagonism or synergy. LY 293111 displays global synergy
      with the active metabolite of irinotecan, SN-38, in the majority of cell lines,
      synergistic to additive effects with gemcitabine in bladder cancer cell lines,
      and synergism with 5'-DFUR (the active metabolite of capecitabine) in two breast
      cancer and one sarcoma cell line. These effects occur at clinically attainable
      concentrations. The addition of a proteosome inhibitor to the LY 293111 and SN-38
      combination markedly enhanced the cytotoxic effects in the sarcoma cell line. As
      the toxicity of LY 293111 in man is not hematological, this agent may have a role
      in combination therapy of selected malignancies.

PMID- 15457129
TI  - Cyclin D and cisplatin cytotoxicity in primary neuroblastoma cell lines.
AB  - Cyclin D1 is a key cell cycle regulator protein with demonstrated oncogenenic
      activity in a variety of malignancies. Overexpression of Cyclin D1 protein has
      been observed in many types of tumors. We hypothesized that Cyclin D1 might be an
      important determinant of the sensitivity of neuroblastomas to cisplatin. Cyclin
      D1, D2 and D3, and Cdk4, Cdk6 and Rb protein, and Cyclin D1 mRNA expression were
      measured in primary patient-derived neuroblastoma cell lines. Cell cycle
      distribution was examined using flow cytometry. A modified MTT assay was used to
      determine the sensitivity of the cell lines to cisplatin. All 14 cell lines
      expressed Cyclin D1 protein to a variable extent (0.22-1.47 normalized to actin
      protein expression). All cell lines expressed Cyclin D2 and D3. There was no
      relationship between expression of Cyclin D1 and expression of Cyclin D2 or D3
      (p>0.05 and R2<0.2 for both). All cell lines expressed Cdk4 and Cdk6 protein. In
      addition, Rb and two related proteins, p105 and p130, were detected in all the
      cell lines. The mean cisplatin IC50 was 19.2 microM (range 0.6-40 microM). We
      conclude that there was no correlation between the amount of Cyclin D1 expressed
      and the cisplatin IC50. Our results do not support the hypothesis that Cyclin D1
      expression is significantly related to cisplatin resistance.

PMID- 15457130
TI  - Tamoxifen and epigallocatechin gallate are synergistically cytotoxic to MDA-MB
      231 human breast cancer cells.
AB  - High concentrations of specific catechins [epigallocatechin gallate (EGCG),
      epigallocatechin (EGC) and epicatechin gallate (ECG)] inhibit the proliferation
      of many different cancer cell lines. The aim of this work was to determine if low
      concentrations of catechins with and without 4-hydroxytamoxifen (4-OHT) co
      treatment would cause significant cytotoxicity in estrogen receptor-positive
      (ERalpha+) and -negative (ERalpha-) human breast cancer cells. Therefore, MCF-7,
      T47D, MDA-MB-231 and HS578T cells were incubated with EGCG, EGC or ECG (5-25
      microM) individually and in combination with 4-OHT for 7 days. Cell number was
      determined by the sulforhodamine B cell proliferation assay. As single agents,
      none of the catechins were cytotoxic to T47D cells, while only EGCG (20 microM)
      elicited cytotoxicity in MCF-7 cells. Additionally, no benefit was gained by
      combination treatment with 4-OHT. ERalpha- human breast cancer cells were more
      susceptible as all three catechins were significantly cytotoxic to HS578T cells
      at concentrations of 10 microM. In this cell line, combination with 4-OHT did not
      increase cytotoxicity. However, the most striking results were produced in MDA-MB
      231 cells. In this cell line, EGCG (25 microM) produced a greater cytotoxic
      effect than 4-OHT (1 microM) and the combination of the two resulted in
      synergistic cytotoxicity. In conclusion, low concentrations of catechins are
      cytotoxic to ERalpha- human breast cancer cells, and the combination of EGCG and
      4-OHT elicits synergistic cytotoxicity in MDA-MB-231 cells.

PMID- 15457131
TI  - Cytotoxic effect of different camptothecin formulations on human colon carcinoma
      in vitro.
AB  - Two innovative 20-S-camptothecin (CPT) formulations, previously found suitable to
      achieve therapeutically relevant CPT concentrations, were assessed for their in
      vitro cytotoxic potential as compared to an aqueous CPT solution, using the MTT
      assay. The formulations, cationic CPT-containing liposomes (CPT-Lip),
      hydroxypropyl-beta-cyclodextrin (HP-beta-CD) complexed CPT (CPT-CD) and a
      saturated aqueous CPT solution (CPT-Sol), were diluted in culture medium to
      appropriate CPT concentrations (4.7-300 ng/ml), and incubated with HT-29 and SW
      480 human colon carcinoma cell lines. IC50 values were calculated after 48 and 72
      h incubation for the HT-29 and SW-480 cell lines, respectively, and were found to
      be of the same magnitude for all formulations, with only a slight difference (CPT
      Sol<CPT-CD<CPT-lip). The cells obtained apoptotic morphology after 36 h
      incubation with CPT-CD and were demonstrated to be active caspase-3 immuno
      positive. Both formulations investigated, CPT-CD and CPT-Lip, showed significant
      cytotoxicity in vitro relative to CPT-Sol and warrant investigation for future
      therapeutic application.

PMID- 15457132
TI  - AK37: the first pyridoacridine described capable of stabilizing the topoisomerase
      I cleavable complex.
AB  - Pyridoacridines are marine natural products that contain planar structures.
      Almost all are cytotoxic and capable of DNA intercalation. Several
      pyridoacridines have demonstrated anti-cancer activity, being able to generate
      reactive oxygen species or to inhibit topoisomerase (Topo) II. Synthetic
      pyridoacridines were characterized and compared to other pyridoacridines as well
      as the Topo-inhibiting drugs (etoposide, 9-aminocamptothecin and wakayin) in a
      series of in vitro enzyme systems. We found AK37 was able to stabilize a DNA-Topo
      I cleavable complex, but not a DNA-Topo II cleavable complex. To our knowledge,
      this is the first report of a DNA-Topo I cleavable complex stabilizing
      pyridoacridine. Structure comparison studies demonstrated that this activity was
      lost when an extra 'F' ring was added, but activity was not affected when the 'D'
      ring was removed. AK37 inhibited the catalytic activity of both human Topo I and
      II.

PMID- 15457133
TI  - Combined effect of recombinant CD19 x CD16 diabody and thalidomide in a
      preclinical model of human B cell lymphoma.
AB  - Combining different treatment strategies offers the possibility of improving
      treatment results for cancer patients. The aim of our study was therefore to
      investigate the combination of treatment of established s.c. human B non
      Hodgkin's lymphoma in severe immune deficient mice using a recombinant bispecific
      CD19 x CD16 diabody (targeting natural killer cells to CD19 cells) and the
      angiogenesis inhibitor thalidomide. Monotherapy with either thalidomide or
      diabody caused an approximate 50% reduction in tumor growth rate. The combined
      treatment showed evidence for a synergistic effect resulting in a 74% reduction
      in median tumor size. In the combined treatment group, two of five animals had
      complete remissions of their s.c. tumor. These results suggest that a combination
      treatment with recombinant diabodies and angiogenesis inhibition represents a
      useful approach in cancer therapy.

PMID- 15457134
TI  - Current issues in nutritional management of very low birth weight infants.
AB  - Infants less than 1,500 g birth weight (very low birth weight, VLBW) are at risk
      for significant nutritional deficiencies. Enhancing nutritional care of these
      infants during their first months of life may have important short and long-term
      benefits. In this article we will consider several areas of recent research in
      the nutritional management of VLBW infants. In particular we will focus on issues
      related to the introduction and use of enteral nutrition. These issues include
      avoiding mineral deficiencies, early (minimal) enteral nutrition, human milk
      fortification, and postdischarge nutrition. Transitioning VLBW infants
      successfully to enteral nutrition is a key to their achieving adequate growth and
      development without the long-term risks related to parenteral nutrition. Human
      milk is a key component of any strategy for enteral nutrition of all infants. Its
      introduction in the first days of life leads to improved growth and better health
      outcomes for infants. However, although some nutrients are initially increased in
      the milk of mothers delivering prematurely, there are inadequate amounts of
      calcium, phosphorus, zinc and other nutrients to meet the needs of the VLBW
      infant during growth. Therefore, safe and effective means of fortifying human
      milk are essential to the care of VLBW infants. The optimal approaches for this
      fortification and the potential risks related to human milk fortification remain
      controversial. Limited data are available for the optimal content, initiation and
      methods for mixing fortifier with human milk.

PMID- 15457135
TI  - Care of very low birth weight infants with respiratory distress syndrome: an
      evidence-based review.
AB  - Since 1959, when it was reported that many preterm infants had surfactant
      deficiency, there has been a remarkable improvement in the prevention of
      respiratory distress syndrome (RDS) and in the care of infants who develop RDS.
      Antenatal corticosteroids and surfactant replacement have improved the care of
      very low birth weight infants.

PMID- 15457136
TI  - Role of oxidative stress as physiopathologic factor in the preterm infant.
AB  - Oxidative stress usually occurs when the production of damaging free radicals
      (ROS) and other oxidative molecules exceeds the capacity of the body's
      antioxidant defenses. This process is supposed to begin after the delivery, but
      it can even affect the fetus when maternal pregnancy diseases (i.e.: pre
      eclampsia, eclampsia, maternal infections) occur and in the case of preterm
      delivery. Most living organisms have developed well integrated antioxidant
      defenses to prevent the potential negative role of the ROS, in order to scavenge
      them and to control their concentration. These mechanisms are deficient in
      preterm newborn. Many illnesses in preterm infants, including bronchopulmonary
      dysplasia (BPD), retinopathy of prematurity (ROP), brain injury such as
      hypoxic/ischemic encephalopathy, and intraventricular hemorrhage (IVH) are
      thought to be related to the action of ROS. This presumably occurs due to the
      fact that the antioxidant system of preterm infants is at the same time highly
      stressed and incompletely developed. Unfortunately, the clinical trials which
      tried to prevent oxidative stress using antioxidant agents failed their objective
      and therefore they cannot be considered as an effective therapy. The objective of
      this review is to clarify the role of oxidative stress in the development of the
      previous severe diseases in preterm infants, and its possible correlation with
      hyperbilirubemia.

PMID- 15457137
TI  - [Eating behaviour and body image: epidemiological study on 4,243 senior and
      junior high school's Italian students].
AB  - AIM: This preliminary study is focused on the description of some dysfunctional
      perceptions of the body's image and eating habits in a large sample of Italian
      adolescents. METHODS: A total of 4,243 secondary school adolescents were examined
      in the Tuscany and Liguria regions in north-west Italy. The age of the 2,024 male
      and 2,219 female adolescents ranged from 12 to 18 years. The Pisa Survey for
      Eating Disorder (PSED), a questionnaire aimed at examining eating behaviour and
      self perception of the body image, was administered. RESULTS: Answers given to
      items considered in this preliminary study have highlighted the recurrence of
      cognitive distortions and an excessively rigid attitude to bodily self
      perception, not to mention frequent and often daily dysfunctional eating
      behaviour. Particularly, females show a more severe attitude to their own body, a
      stronger desire to lose weight and more resolution to follow a diet. It is also
      true to say that girls present more often than their male peers irregular eating
      habits and moments of overeating. Also the recourse to self-induced vomiting, or
      other coercive expedients, appears to be more typical of female behaviour though
      this practice was widespread throughout the sample. CONCLUSIONS: The PSED
      questionnaire has proved to be a useful tool in revealing eating habits and self
      perception in the examined sample. The results obtained confirm the urgent need
      for educational and preventive intervention.

PMID- 15457138
TI  - [Neurological and psychological evolution of adolescents with vertical
      transmission HIV infection].
AB  - AIM: Personal experience in a sample group of children with AIDS vertically
      transmitted followed from birth to adolescence (out of 56 cases with documented
      HIV infection, 9 who have reached the age of 13 have been studied) is presented.
      METHODS: The evaluation protocol includes: hematochemical, serological and
      virological tests to monitor the infectious status, as well as annual EEG, CT/MRI
      scan to detect anatomical alteration of CNS, neurological examination,
      intelligence test (WISC-R), interview and projective test (Blacky Pictures) to
      investigate emotional situation. RESULTS: As to the status of the disease,
      according to the CDC classification, 2 patients are asymptomatic, 2
      paucisymptomatic, 2 with moderate symptoms, 2 severely symptomatic; 1 patient
      died due to progressive encephalopathy. Of the 2 severely symptomatic cases, 1
      presents cortical atrophy and the other basal nuclei calcifications. No one of
      them has clinical signs of encephalopathy. All patients receive anti-retroviral
      medications. From tests and interviews emotional problem-emerge, future is seen
      as menacing and insidious, and defensive mechanisms are fragile and inconstant;
      denial can lead to a refusal of the pharmacological therapy; families themselves
      often refuse medical staff the consent to communicate the diagnosis fearing that
      this could induce unbearable anguish. CONCLUSIONS: It seems important that
      patients are informed, considering their capacity to make front to the
      communication, even if one must bear in mind that understanding and accepting the
      diagnosis may be a long and painful process requiring a long time.

PMID- 15457139
TI  - Intrapleural fibrinolytic treatment of multiloculated pediatric empyemas.
AB  - AIM: The aim of this paper was to compare the efficacy of adjunctive intrapleural
      fibrinolygic agents (streptokinase, urokinase) on fibrinopurulent stage empyema
      and chronic stage empyema. METHODS: In our clinic, we used intrapleural
      fibrinolytic agents in 78 pediatric patients (36 fibrinopurument stage empyemas,
      42 chronic stage empyemas) between December 1994 and September 2002. Pleural
      biopsy was done for staging. Streptokinase 250,000 units in 100 ml 0.9% saline
      solution (62 patients) and 125000 units in 100 ml 0.9% saline solution (16
      patients) was instilled daily to the chest tube, and the tube was clamped for 4 h
      followed by suction. This treatment was continued daily for 2 to 8 days until
      resolution was demonstrated by chest radiograms and/or computed chest tomography.
      RESULTS: The treatment was discontinued due to allergic reaction and pleural
      hemorrhage in 1 patient with fibrinopurulent empyema. This patient died 1 day
      later in a septic condition. The regimen was completely successful in 24/36
      (66.6%) fibrinopurulent empyemas, and partially successful in other 11/36
      (30.55%). Treatment was ineffective in 38 of 42 patients with chronic empyemas
      (90.6%). Two cases in chronic phase empyema completely recovered and 2 other
      patients had a partial response. Success of the treatment was 91.66% (35/36)
      (complete response: 24/36' partial response 11/36) in the fibropurulent stage and
      9.4% (2/42 complete response, 2/42 partial response in chronic cases.
      CONCLUSIONS: Our study suggests that intrapleural fibrinolytic treatment is an
      effective and safe therapy in children with fibrinopurulent phase thoracic
      empyema.

PMID- 15457140
TI  - Colostomy type in anorectal malformations: 10-years experience.
AB  - AIM: The aim of this study was to evaluate the influence of colostomy type on
      morbidity during the treatment of anorectal malformations. METHODS: Sixty-eight
      infants (male: female ratio 1.3:1) with anorectal malformations that required
      colostomy were treated in our clinics during the period 1991-2001. Of these
      patients, 26 had received a loop colostomy: 14 of these underwent posterior
      sagittal anorectoplasty (PSARP) at the age of 9-12 months (Group A), and 12
      underwent PSARP at the age of 2-4 months (Group B). Forty-two infants received a
      separated-stomas colostomy and underwent PSARP at the age of 9-12 months (Group
      C). The incidence of complications among groups was compared using the 2 sided
      Fisher's exact test. RESULTS: Eight cases from group A were complicated with
      prolapse of the stomas, perianal wound infection, pull-through dehiscence, and
      anal fibrotic stricture. The only complication observed in groups B and C was
      perianal wound infection, which occurred in 1 case from each group. A
      statistically significant difference was observed in the incidence of
      complication between groups A and C (p<0.001) and between groups A and B
      (p=0.014). The results from groups B and C did not differ significantly
      (p=0.398). When the cases complicated with colostomy prolapse were removed from
      the statistical analysis, groups A and C still differed significantly (p=0.001)
      but groups A and B did not (p=0.069). CONCLUSIONS: As the incidence of
      complications increases with time after a loop colostomy, we encourage either an
      early corrective procedure or the modification into separated-stomas colostomy
      (SSC) before PSARP is performed for those cases that would involve definitive
      surgery in late infancy.

PMID- 15457141
TI  - [School in hospital: an opportunity for the hospitalized child to overcome the
      illness risk].
AB  - AIM: The paper reports research on the subject of "Overcoming the illness risk in
      the School in Hospital service" the aim of which was to monitor this particular
      service so as to assess whether or not the activities proposed are directed by
      the model of overcoming inherent risks as defined and reported here. Four
      research directions were taken to verify the hypothesis whereby the service takes
      on a supportive-transformative value which enables the hospitalized child to
      study through his/her illness and is thus able to develop by activating support,
      protection and diagnosis functions. METHODS: The investigation was carried out
      using the single case methodology which provided for continuous observation
      lasting for the entire hospital period in the paediatric wards of 2 hospital in
      Sicily. The research involved 58 children aged between 7 and 12; chronically ill
      or long-stay patients, and 100 mothers of hospitalized children. The research
      also observed the effects of the intervention activated by "School in Hospital"
      on the child and on his reference models. Various instruments of an
      observational, projective and psycho-social investigation type were utilized in
      relation to the 2 main subjects of the research, the development outcomes on the
      subjects involved and the activities proposed by the service. RESULTS: The
      overall results confirm the supportive-transformative value of the "School in
      Hospital" service. CONCLUSIONS: The data obtained suggest that the service should
      be promoted within hospital structures as a specific form of the caring approach.

PMID- 15457142
TI  - Dissociative disorder in children. A case study.
AB  - Dissociative disorder is well-known in adulthood but in many cases it begins in
      childhood where it is usually not taken into consideration, rarely diagnosed, and
      often mistaken with borderline disorders. In childhood dissociation is well
      defined: in a dimensional way by the presence of the dissociation symptoms over 2
      SD and in a categorial view by the presence of primary symptoms. We made a
      psychiatric assessment on a child aged 11 years and 7 months, who said he heard
      "voices in his head". The assessment included: Children Dissociative Checklist
      (CDC), Adolescent Dissociative Experience Scale (A-DES), Children Depression
      Inventory (CDI), Wechsler Intelligence Scales for Children-Revised (WISC-R),
      Strength and Difficulties Questionnaire (SDQ), Children Behaviour Check-list
      (CBCL), (Scale Disturbi Attenzione Genitori, parent attention deficit scale,
      SDAG), Parent Conners Questionnaire, free conversation, a drawing, a neurological
      examination, an EEG-Holter and a semistructured psychiatric interview: K-SADS PL
      1.0. SDQ, CDI and CBCL showed pathological scores in every area. K-SADS PL 1.0
      excluded schizophrenia and showed: attention deficit, disthymic disorder,
      generalized anxiety disorder, oppositive-defiant disorder and conduct disorder
      with rage episodes, like borderline disorder. I.Q. was 76, SDAG (total 46) and
      Conners (mean points 1.81) showed a high score, simulating Attention Deficit with
      Hyperactivity disorder (ADHD). The presence of primary symptoms, like
      dissociative amnesia and very high scores in CDC (23, mean score for MPD) and in
      A-DES (85, mean 4.2) are useful for diagnoses. Dissociative disorder also exists
      in childhood, but it should be differentiated from ADHD and borderline disorder.

PMID- 15457143
TI  - [Oligodontia. A case report].
AB  - "Oligodontia" is the absence of 6 or more teeth, except the third molars. Genetic
      factors are important in determining hypodontia: in fact, this is an autosomal
      dominant trait relatively common in population. In particular, the agenesis of
      lateral incisors is fairly common, with autosomal dominant and variable
      expression inheritance. The incidence of hypodontia in primary dentition is 0.1
      0.7% and there is no difference between females and males; instead, hypodontia in
      permanent dentition is most common in females compared with males and the
      incidence is 6-10% in general population. Oligodontia can interfere with the
      maxillofacial skeleton growth in children and adolescents. This problem must be
      tackled by paying attention to the physical and psychological development of the
      patient. A case of oligodontia in an 8-year-old-boy without 17 permanent teeth
      likely related to a variable expression genetic disorder is reported. The medical
      examination of the boy was completely negative, with the exception of the
      dentition. The child will be followed to value any possible maxillofacial
      abnormalities that might need an early therapy. The definitive therapeutic
      approach will be carried out, as soon as possible, using oral endo-osseous
      systems to allow normal masticatory and phonetic function.

PMID- 15457144
TI  - High-risk sexual behavior by HIV-positive men who have sex with men--16 sites,
      United States, 2000-2002.
AB  - The majority of persons living with human immunodeficiency virus (HIV) in the
      United States are men who have sex with men (MSM). High-risk sexual behavior by
      HIV-positive MSM exposes sex partners to HIV. The risk for transmitting HIV from
      an infected partner to an uninfected partner through unprotected insertive anal
      intercourse (UIAI) is greater than the risk for transmission through receptive
      anal intercourse or oral sex. Differences in sexual risk behavior might be
      associated with the perceived HIV serostatus of the partner (i.e., HIV positive,
      HIV negative, or unknown serostatus), as well as with the sex partner type (i.e.,
      steady or nonsteady). During May 2000-December 2002, HIV-positive MSM were
      interviewed in a behavioral surveillance survey at surveillance sites in 16
      states. This report describes insertive anal intercourse practices reported by
      these MSM; findings indicated that a large percentage of HIV-positive MSM were
      sexually abstinent, practiced safer sexual behavior by having protected insertive
      anal intercourse, or had UIAI with an HIV-positive partner. However, a small
      percentage of HIV-positive MSM reported UIAI with partners who were HIV negative
      or whose serostatus was unknown; for this group, more intensive and comprehensive
      HIV-prevention efforts are needed to eliminate this risk behavior.

PMID- 15457145
TI  - Imported Lassa fever--New Jersey, 2004.
AB  - Lassa fever is an acute viral illness caused by Lassa virus, which is hosted by
      rodents in the Mastomys natalensis species complex and rarely imported to
      countries outside of those areas in Africa where the disease is endemic. Lassa
      fever is characterized by fever, muscle aches, sore throat, nausea, vomiting, and
      chest and abdominal pain. Approximately 15%-20% of patients hospitalized for
      Lassa fever die from the illness; however, approximately 80% of human infections
      with Lassa virus are mild or asymptomatic, and 1% of infections overall result in
      death. On August 28, 2004, a man aged 38 years residing in New Jersey died from
      Lassa fever after returning from travel to West Africa. This report summarizes
      the clinical and epidemiologic investigations conducted by federal, state, and
      local public health agencies. The findings illustrate the need for clinicians and
      public health officials to remain alert to emerging infectious diseases and to
      institute appropriate measures to promptly identify and limit spread of unusual
      pathogens.

PMID- 15457146
TI  - Emergency measles control activities--Darfur, Sudan, 2004.
AB  - The Darfur region of Sudan, composed of three states with a population of
      approximately six million, has experienced civil conflict during the previous
      year, resulting in the internal displacement of approximately one million
      residents and an exodus of an estimated 170,000 persons to neighboring Chad. The
      conflict has left a vulnerable population with limited access to food, health
      care, and other basic necessities. In addition, measles vaccination coverage has
      been adversely affected; in 2003, coverage was reported to be 46%, 57%, and 77%
      in North, West, and South Darfur, respectively. This report describes measles
      control activities in Darfur region conducted by the Federal Ministry of Health
      (FMOH) in Sudan in collaboration with the United Nations and nongovernmental
      organizations (NGOs) during March-August 2004. Ongoing measles transmission in
      camps for internally displaced persons (IDPs) and neighboring communities in
      Darfur led to a regionwide measles vaccination campaign targeting all children
      aged 9 months-15 years, resulting in a reduction in reported measles cases. Once
      security is improved, ongoing efforts to increase measles vaccine coverage will
      be required to eliminate persistent susceptibility to measles in the Darfur
      population.

PMID- 15457147
TI  - West Nile virus activity--United States, September 22-28, 2004.
AB  - During September 22-28, a total of 180 cases of human West Nile virus (WNV)
      illness were reported in the District of Columbia (DC) and 24 states (Alabama,
      Arizona, California, Georgia, Illinois, Iowa, Kansas, Kentucky, Louisiana,
      Maryland, Michigan, Minnesota, Mississippi, Missouri, Montana, Nebraska, Nevada,
      New Mexico, Ohio, Pennsylvania, Texas, Utah, Wisconsin, and Wyoming).

PMID- 15457148
TI  - Reflections on reduction ascending aortoplasty's liveliness.

PMID- 15457149
TI  - Catamenial pneumothorax revisited: clinical approach and systematic review of the
      literature.
AB  - BACKGROUND: Catamenial pneumothorax is a rare entity of spontaneous, recurring
      pneumothorax in women. It has been associated with thoracic endometriosis, yet
      varying clinical courses and the lack of consistent intraoperative findings have
      led to conflicting etiologic theories. METHODS: We discuss etiology, clinical
      course, and surgical treatment of 3 women with catamenial pneumothorax. In
      addition, the world literature since the first description is reviewed. RESULTS:
      Three women (31, 32, and 39 years old) had recurrent, menses-associated, right
      sided spontaneous pneumothoraces. They had undergone video-assisted thoracoscopic
      surgery previously, with various unsuccessful procedures. Finally, with video
      assisted thoracoscopic surgery multiple small perforations in the tendinous part
      of the right diaphragm with adjacent endometrial implants were detected. After
      plication of the involved area, 2 patients have been free of recurrence for 22
      and 13 months, respectively. Laparoscopic evaluation in 1 woman with a further
      recurrence revealed asymptomatic pelvic endometriosis. This patient has been free
      of recurrence since initiation of luteinizing hormone-releasing hormone analog
      therapy for 17 months. In a review of 229 cases of catamenial pneumothorax in the
      literature, adequate information was given for 195 patients (85.2%). One hundred
      fifty-four (79%) were treated surgically, with detailed findings reported for 140
      (91%). Thoracic endometriosis was diagnosed in 73 patients (52.1%), and 54
      (38.8%) showed diaphragmatic lesions. Pleurodesis, with or without diaphragmatic
      repair or wedge resection, was performed in 81.7% of the cases. CONCLUSIONS:
      Catamenial pneumothorax may be suspected in ovulating women with spontaneous
      pneumothorax, even in the absence of symptoms associated with pelvic
      endometriosis. During video-assisted thoracoscopic surgery, inspection of the
      diaphragmatic surface is paramount. Plication of the involved area alone can be
      successful. In complicated cases, hormonal suppression therapy is a helpful
      adjunct.

PMID- 15457150
TI  - Reoperative laparoscopic fundoplication for the treatment of failed
      fundoplication.
AB  - OBJECTIVE: This study was undertaken to determine the safety and efficacy of
      reoperative laparoscopic fundoplication for patients with failed fundoplication.
      METHODS: Thirty-nine of 612 consecutive patients who had undergone fundoplication
      underwent laparoscopic reoperative fundoplication for recurrent symptoms,
      persistent dysphagia, or gas bloat. An additional 15 patients were referred from
      outside facilities for reoperation. Preoperative evaluation included barium
      swallow (n = 54), esophagogastroduodenoscopy (n = 54), esophageal manometry (n =
      34), and 24-hour ambulatory pH measurement (n = 32). Symptom severity before and
      after surgery was evaluated with a visual analog scoring scale. The mean follow
      up was 22.5 months. RESULTS: The primary symptoms that led to reoperation in the
      54 patients were heartburn (n = 26), dysphagia (n = 23), and gas bloat (n = 5).
      Average time from initial operation to reoperation was 22.7 months. There were 3
      conversions to open technique. An anatomic reason for the failure of the initial
      fundoplication was found in 69% of cases: slipped or misplaced fundoplication (n
      = 14), disrupted fundoplication (n = 8), transdiaphragmatic herniation (n = 7),
      achalasia (n = 1), and tight fundoplication (n = 7). Fourteen patients had 15
      perioperative complications. Mean hospital stay was 2.3 days. Symptoms such as
      heartburn, dysphagia, and gas bloat improved significantly after reoperation; 40%
      to 50% of patients had scores 0 to 2, 21% to 45% had scores 3 to 7, and 9% to 29%
      had scores 8 to 10. Proton-pump inhibitor use after operation decreased from 88%
      to 36%. Fifty-two percent of patients completely discontinued any antireflux
      medications. Three patients had failure of the reoperation and required
      additional procedures. CONCLUSION: Laparoscopic reoperation for failed
      fundoplication is feasible and can achieve resolution of symptoms for a
      significant percentage of patients.

PMID- 15457151
TI  - Vascular endothelial growth factor expression in metastatic pulmonary tumor from
      colorectal carcinoma: utility as a prognostic factor.
AB  - OBJECTIVE: To define the most reliable prognostic factor, we studied the 5-year
      survival of patients after resection of pulmonary metastases from colorectal
      cancer in relation to various prognostic factors, including vascular endothelial
      growth factor expression in primary and metastatic tumors. METHODS: A
      retrospective study was undertaken in 49 patients who had undergone complete
      resection of pulmonary metastasis from colorectal carcinoma. All patients were
      retrospectively analyzed for sex, age, location and stage of primary tumor,
      number of pulmonary metastases, type of pulmonary resection, size of metastatic
      tumor, lymph node metastasis, and prethoracotomy carcinoembryonic antigen level.
      Furthermore, vascular endothelial growth factor expression of both primary and
      metastatic tumors was investigated. RESULTS: Overall 5-year survival was 34.3%.
      In the univariate analysis the number of pulmonary metastases (P =.007) and
      vascular endothelial growth factor expression in metastatic tumors (P =.008) and
      primary colorectal tumors (P =.011) were significantly associated with poor
      survival. In the multivariate analysis the number of pulmonary metastases (P
      =.0031), vascular endothelial growth factor expression in metastatic tumors (P
      =.0057), and stage of primary tumor (P =.0321) were characteristics that retained
      a significant independent prognostic effect on overall survival. A statistically
      significant difference was not found in the 5-year survival of patients with
      solitary and negative vascular endothelial growth factor expression in metastatic
      tumors (59.1%) versus those with multiple and positive vascular endothelial
      growth factor expression in metastatic tumors (10.0%; P <or=.0001). CONCLUSIONS:
      Vascular endothelial growth factor expression in metastatic pulmonary tumors is
      an important prognostic marker for patients with pulmonary metastasis from
      colorectal carcinoma. Our results suggested that patients with multiple and
      positive vascular endothelial growth factor expression in the metastatic tumor
      will not receive benefit from metastasectomy.

PMID- 15457152
TI  - Resectional surgery combined with chemotherapy remains the treatment of choice
      for multidrug-resistant tuberculosis.
AB  - OBJECTIVE: Multidrug-resistant tuberculosis remains a significant health problem.
      The best available treatment for multidrug-resistant tuberculosis is the
      combination of pulmonary resection and antituberculous chemotherapy. We herein
      report the results of pulmonary resection combined with chemotherapy for
      multidrug-resistant tuberculosis at our institution during the years 2000 through
      2002. METHODS: Between 1983 and 2002, 87 patients underwent 95 pulmonary
      resections for multidrug-resistant tuberculosis. Of these, the 30 (34%) patients
      operated on from January 1, 2000, to December 31, 2002, are reviewed in the
      present study. All patients were maintained on multidrug regimens preoperatively
      and postoperatively. Indications for surgical intervention included persistently
      positive sputum and a high risk of relapse. Thirty-three pulmonary resections
      were performed, consisting of pneumonectomy (n = 12), lobectomy (n = 17), and
      segmentectomy (n = 4). The bronchial stump was reinforced with a latissimus dorsi
      muscle flap in 29 resections. RESULTS: There was no operative mortality.
      Bronchopleural fistulas occurred in 2 patients. Five patients had a space
      problem. All patients attained sputum-negative status after the operation.
      Relapse occurred in 3 patients: 2 had a relapse at the bronchial stump, and the
      remaining patient had a relapse in the postlobectomy space. One late death
      occurred. Of the 29 survivors, 27 (93%) were free from disease, with a median
      follow-up of 24 months (range, 8-47 months). CONCLUSIONS: An increasing number of
      patients with multidrug-resistant tuberculosis are requiring resectional surgery
      in the 21st century. Pulmonary resection combined with chemotherapy achieves high
      cure rates with acceptable morbidity and remains the treatment of choice for
      multidrug-resistant tuberculosis.

PMID- 15457153
TI  - Homograft replacement of the mitral valve: eight-year results.
AB  - OBJECTIVE: The objective of this study was to assess whether the mitral homograft
      represents a valuable alternative for complete or partial mitral valve
      replacement. METHODS: Since 1993, 104 patients underwent mitral homograft
      replacement surgery. The mean age was 38 +/- 15 years. The causes of mitral valve
      disease were rheumatic disease (n = 76), infective endocarditis (n = 24), and
      others (n = 4). Sixty-five of these procedures were total homografts, and 39 were
      partial homografts. RESULTS: The mean follow-up was 52 +/- 35 months (maximum,
      117 months). Overall hospital mortality was 4 (3.8%) of 104 patients and 2.5%
      versus 8.7% for patients without endocarditis and with endocarditis, respectively
      (P <.19). There were 9 late deaths (cardiac, 4; noncardiac, 5). There have been 5
      early (<3 months) and 10 late reoperations. Of the remaining 77 patients, New
      York Heart Association class was I in 61, II in 14, and III in 2. Four patients
      had endocarditis, and 5 had an ischemic or hemorrhagic event. Freedom from major
      cardiac events was 71% +/- 6% at 8 years (partial at 81% vs total at 63%, P
      <.19). Among patients with a total homograft, freedom from major cardiac events
      was 61% +/- 9% and 85% +/- 8% at 6 years in patients younger than and older than
      40 years, respectively (P =.09). CONCLUSION: The risk of early dysfunction
      related to a mismatch between the mitral homograft and the patient's valve is the
      main pitfall of the technique. Beyond that stage, the results were comparable
      with those of bioprostheses in a cohort of young patients.

PMID- 15457154
TI  - A prospective, single-center clinical trial of a modified Cox maze procedure with
      bipolar radiofrequency ablation.
AB  - OBJECTIVE: The Cox maze III procedure has excellent long-term efficacy in curing
      atrial fibrillation. It has not been widely practiced because it is technically
      challenging and requires prolonged cardiopulmonary bypass. The aim of this study
      was to examine a simplified Cox maze III procedure that uses bipolar
      radiofrequency energy as an ablative source. METHODS: Beginning January 2002, a
      total of 40 consecutive patients underwent a modified Cox maze III procedure with
      bipolar radiofrequency energy. Nineteen had a lone maze procedure and 21 had a
      maze procedure plus a concomitant operation. One month after the operation, the
      first 8 patients were investigated with high-resolution magnetic resonance
      imaging. Patients were followed up monthly with clinical examination and
      electrocardiography. RESULTS: There was no operative deaths. The crossclamp times
      were 47 +/- 26 minutes for the modified lone Cox maze III procedure and 92 +/- 37
      minutes for the Cox maze III procedure plus concomitant procedures. These were
      significantly shorter than our previous times for the traditional Cox maze III
      procedure (93 +/- 34 minutes and 122 +/- 37 minutes, respectively, P <.05).
      Follow-up magnetic resonance imaging showed no evidence of pulmonary vein
      stenosis, and atrial contractility was preserved in all patients. There were no
      late strokes. At 6-month follow-up, 91% of patients (21/23) were in sinus rhythm.
      CONCLUSIONS: Bipolar radiofrequency ablation can be used to replace the surgical
      incisions of the Cox maze procedure. This energy source did not result in
      pulmonary vein stenosis. The modification of the Cox maze III procedure to use
      bipolar radiofrequency ablation simplified and shortened this procedure without
      sacrificing short-term efficacy.

PMID- 15457155
TI  - Functional mitral regurgitation in chronic ischemic coronary artery disease:
      analysis of geometric alterations of mitral apparatus with magnetic resonance
      imaging.
AB  - BACKGROUND: Patients with chronic coronary artery disease have double the
      mortality rate if the condition is combined with functional mitral regurgitation.
      An understanding based on geometric alterations of the mitral apparatus in
      functional mitral regurgitation is desirable. METHODS: Twenty-nine subjects were
      enrolled in the study, including 9 healthy volunteers (control group), 12
      patients with chronic coronary artery disease without functional mitral
      regurgitation (CAD group), and 8 patients with chronic coronary artery disease
      with functional mitral regurgitation (CAD+FMR group). Cine magnetic resonance
      imaging was performed to acquire multiple short-axis cine images from base to
      apex. Left ventricular end-systolic volume, left ventricular ejection fraction,
      mitral area, and vertices of the mitral tetrahedron, defined by medial and
      lateral papillary muscle roots and anterior and posterior mitral annulus, were
      determined from reconstructed images at end-systole. Anterior-posterior annular
      distance, interpapillary distance, and annular-papillary distance (the distance
      from the anterior or posterior mitral annulus to the medial or lateral papillary
      muscle roots) were calculated. RESULTS: Left ventricular end-systolic volume was
      inversely associated with left ventricular ejection fraction (R(2) = 0.778). Left
      ventricular end-systolic volume was highly associated with distances related to
      ventricular geometry (R(2) = 0.742 for interpapillary distance, 0.792 for the
      distance from the anterior mitral annulus to the medial papillary muscle root,
      and 0.769 for distance from the anterior mitral annulus to the lateral papillary
      muscle root) but was moderately associated with distances related to annular
      geometry (R(2) = 0.458 for anterior-posterior annular distance and 0.594 for
      mitral area, respectively). Moreover, interpapillary distance of greater than 32
      mm and distance from the anterior mitral annulus to the medial papillary muscle
      root of greater than 64 mm readily distinguished the CAD+FMR group from the other
      groups. CONCLUSION: In patients with coronary artery disease, an increase in left
      ventricular end-systolic volume is associated with inadequate approximation of
      the mitral tetrahedron during systole, which consequently leads to functional
      mitral regurgitation. Our study suggests that interpapillary distance and
      distance from the anterior mitral annulus to the medial papillary muscle root are
      sensitive to the increase in left ventricular end-systolic volume and reliably
      indicate the presence of functional mitral regurgitation.

PMID- 15457156
TI  - Clinical pulmonary autograft valves: pathologic evidence of adaptive remodeling
      in the aortic site.
AB  - OBJECTIVE: We studied the pathologic features, cellular phenotypes, and matrix
      remodeling of clinical pulmonary-to-aortic valve transplants functioning up to 6
      years. METHODS: Nine autografts and associated vascular walls early (2-10 weeks)
      and late (3-6 years) postoperatively were examined by using routine morphologic
      methods and immunohistochemistry. In 4 cases autograft and homograft cusps were
      obtained from the same patients. RESULTS: Autografts had near-normal trilaminar
      cuspal structure and collagen architecture and viable valvular interstitial and
      endothelial cells throughout the time course. In contrast, cusps of homografts
      used to replace the pulmonary valves in the same patients were devitalized. In
      early autograft explants, 19.3% +/- 2.4% of cuspal interstitial cells were
      myofibroblasts expressing alpha-actin. In contrast, myofibroblasts comprised only
      6.0% +/- 1.1% of cells in late explants and 2.5% +/- 0.4% and 4.6% +/- 0.8% of
      cells in normal pulmonary and aortic valves, respectively (P <.05). In early
      autografts only 12.0% +/- 4.6% of endothelial cells expressed the systemic
      arterial endothelial cell marker EphrinB2, whereas later explants had 85.6% +/-
      5.4% of endothelial cells expressing EphrinB2 (P <.05). In early autografts 43.8%
      +/- 8.8% of interstitial cells expressed metalloproteinase 13, whereas late
      autografts had 11.4% +/- 2.7% of interstitial cells expressing matrix
      metalloproteinase 13 (P <.05). Collagen content in autografts was comparable with
      that of normal valves and was higher than that seen in homograft valves (P
      <.005). However, autograft walls were damaged, with granulation tissue (early)
      and scarring, with focal loss of normal smooth muscle cells, elastin, and
      collagen (late). CONCLUSIONS: The structure of pulmonary valves transplanted to
      the systemic circulation evolved toward that of normal aortic valves. Key
      processes in this remodeling included onset of a systemic endothelial cell
      phenotype and reversible plasticity of fibroblast-like valvular interstitial
      cells to myofibroblasts.

PMID- 15457157
TI  - Size reduction ascending aortoplasty: is it dead or alive?
AB  - OBJECTIVE: Reduction ascending aortoplasty is a controversial procedure. Some
      believe that it can be appropriately applied when the anatomic features are
      favorable. Others suggest that it should be restricted to those patients who are
      at unacceptably high risk for more radical procedures, and there are also those
      who believe that reduction ascending aortoplasty should not be applied at all.
      The purpose of the article is to draw conclusions on the applicability of
      reduction ascending aortoplasty in modern cardiovascular surgery. METHODS: The
      issue was examined in the mirror of the authors' own experiences, by review and
      scrutiny of the literature available on the subject, and by conducting an
      extensive survey of the profession. RESULTS: We found that given proper
      indications (ie, poststenotic dilatations of <6 cm in diameter, absence of cystic
      medial necrosis, and a technique that decreases aortic diameter to <3.5 cm),
      nonreinforced reduction ascending aortoplasty performed concomitantly with aortic
      valve replacement appears to be a simple and safe procedure, with low morbidity
      and mortality and rare late complications. External reinforcement might extend
      the scope of indication for reduction ascending aortoplasty to ascending aortic
      aneurysms associated with aortic regurgitation and to those with primary
      structural aortic wall disease with comparable results. Experience also has shown
      that late complications might be further reduced by means of proper proximal
      anchoring and extending the wrap past the origin of the innominate artery.
      CONCLUSIONS: We conclude that reduction ascending aortoplasty is certainly alive.
      Although it does not appear to be an extremely popular operation, about half of
      the surgeons who responded believe it to be justified. Regardless of which
      modality is used, lifetime monitoring of ascending aortic size is essential and
      so advised. Because of recent sporadic reports of "under-the-wrap" aortic wall
      atrophy and rupture, the issue of reinforcement of reduction ascending
      aortoplasty requires continued re-evaluation.

PMID- 15457158
TI  - Injectable bioartificial myocardial tissue for large-scale intramural cell
      transfer and functional recovery of injured heart muscle.
AB  - OBJECTIVES: Most tissue-engineering approaches to restore injured heart muscle
      result in distortion of left ventricular geometry. In the present study we
      suggest seeding embryonic stem cells in a liquid matrix for myocardial
      restoration. METHODS: Undifferentiated green fluorescent protein-labeled mouse
      embryonic stem cells (2 x 10 6 ) were seeded in Matrigel (B&D, Bedford, Mass). In
      a Lewis rat heterotopic heart transplant model an intramural left ventricular
      pouch was fashioned after ligation of the left anterior descending coronary
      artery. The liquid mixture (0.125 mL) was injected in the resulting infarcted
      area within the pouch and solidified within a few minutes after transplantation
      (37 degrees C). Five recipient groups were formed: transplanted healthy hearts
      (group I), infarcted control hearts (group II), matrix recipients alone (group
      III), the study group that received matrix plus cells (group IV), and a group
      that received embryonic stem cells alone (group V). After echocardiography 2
      weeks later, the hearts were harvested and stained for green fluorescent protein
      and cardiac muscle markers (connexin 43 and alpha-sarcomeric actin). RESULTS: The
      graft formed a sustained structure within the injured area and prevented
      ventricular wall thinning. The inoculated cells remained viable and expressed
      connexin 43 and alpha-sarcomeric actin. Fractional shortening and regional
      contractility were better in animals that received bioartificial tissue grafts
      compared with control animals (infarcted, matrix only, and embryonic stem cells
      only: group I, 17.0% +/- 3.5%; group II, 6.6% +/- 2.1%; group III, 10.3% +/-
      2.2%; group IV, 14.5% +/- 2.5%; and group V, 7.8% +/- 1.8%). CONCLUSIONS: Liquid
      bioartificial tissue containing embryonic stem cells constitutes a powerful new
      approach to restoring injured heart muscle without distorting its geometry and
      structure.

PMID- 15457159
TI  - Three-dimensional echocardiography-guided beating-heart surgery without
      cardiopulmonary bypass: a feasibility study.
AB  - BACKGROUND: There is no current acceptable approach for intracardiac beating
      heart interventions. We have adapted real-time 3-dimensional echocardiography
      with specialized instrumentation to facilitate beating-heart repair of atrial
      septal defects and mitral valve plasty to investigate the feasibility of real
      time 3-dimensional echocardiography-guided cardiac surgery. METHODS: In
      experiment I a modified real-time 3-dimensional echocardiography system with x4
      matrix transducer was compared with 2-dimensional echocardiography in the
      performance of common surgical tasks. Completion times, deviation from an ideal
      trajectory, and an echogenic target were measured. In experiment II porcine
      atrial septal defects were closed with an original semiautomatic suturing device
      (n = 4) and with a 5-mm endoscopic stapler and a pericardial or
      polytetrafluoroethylene patch (n = 4). In experiment III a pulsatile porcine
      mitral valve model was developed, and suture placement through the anterior and
      posterior mitral leaflets was performed (n = 8). During all experiments, the
      operator was blinded to the target and operated on only with ultrasonic guidance.
      RESULTS: In experiment I, compared with 2-dimensional echocardiographic guidance,
      completion times improved by 21% ( P <.01) with high-trajectory accuracy, and
      suture deviation was significantly smaller (2-dimensional echocardiography, 5.4
      +/- 2.7 mm; 3-dimensional echocardiography, 1.7 +/- 0.7 mm; P <.05) in real-time
      3-dimensional echocardiography-guided tasks. In experiments II and III in both
      atrial septal defect closure and mitral valve plasty, real-time 3-dimensional
      echocardiography provided satisfactory images and sufficient anatomic detail for
      suturing and patch deployment. All surgical tasks were successfully performed
      with accuracy. CONCLUSIONS: Real-time 3-dimensional echocardiography provides
      adequate imaging and anatomic detail to act as a sole guide for surgical task
      performance. These initial experiments demonstrate the feasibility of beating
      heart direct or patch closure of atrial septal defects and mitral valve plasty
      without cardiopulmonary bypass.

PMID- 15457160
TI  - FR167653 diminishes infarct size in a murine model of myocardial ischemia
      reperfusion injury.
AB  - OBJECTIVE: During myocardial ischemia-reperfusion injury, p38 mitogen-activated
      protein kinase is activated. We examined the effect of a highly specific
      inhibitor of p38 mitogen-activated protein kinase, FR167653, in an experimental
      model of regional myocardial ischemia-reperfusion. METHODS: CD-1 mice received
      FR167653 intraperitoneally 24 hours before 30 minutes of transient occlusion of
      the left anterior descending artery, followed by 120 minutes of reperfusion. The
      p38 mitogen-activated protein kinase activation and kinase activity were
      determined by Western blotting with monoclonal antibodies for the phosphorylated
      from of p38 mitogen-activated protein kinase or its substrate, activating
      transcription factor 2. Nuclear factor kappaB activity was measured by detecting
      translocation of nuclear factor kappaB to the nucleus. The expression of
      inflammatory cytokines was measured by ribonuclease protection assay. RESULTS:
      Pretreatment of mice with FR167653 before myocardial ischemia-reperfusion
      resulted in a reduction in p38 mitogen-activated protein kinase phosphorylation
      (P =.018), an inhibition of p38 mitogen-activated protein kinase activity (P
      =.047), a smaller amount of nuclear factor kappaB (P =.001), and a decrease in
      the expression of inflammatory cytokines (tumor necrosis factor alpha: P =.023,
      interleukin 1beta: P =.038, monocyte chemotactic protein 1: P =.0001) in the
      heart and the development of a significantly smaller infarct (P =.0069) relative
      to hearts from mice treated with vehicle alone. Activation of c-Jun N-terminal
      kinase and extracellular signal-regulated kinase were observed after myocardial
      ischemia-reperfusion without inhibition by FR167653. CONCLUSION: We conclude that
      FR167653 selectively inhibits p38 mitogen-activated protein kinase activation and
      activity during regional myocardial ischemia-reperfusion injury and efficaciously
      reduces infarct size (by 73.6%). Thus p38 mitogen-activated protein kinase
      inhibition may have a role in the treatment of myocardial ischemia-reperfusion.

PMID- 15457161
TI  - Homozygous deletion of early growth response 1 gene and critical limb ischemia
      after vascular ligation in mice: evidence for a central role in vascular
      homeostasis.
AB  - BACKGROUND: The early growth response 1 gene (Egr1) encodes for an immediate to
      early response transcription factor that is upregulated by changes in vascular
      strain and hypoxia and in turn upregulates the downstream expressions of a number
      of angiogenic growth factors. We therefore hypothesized that early growth
      response 1 may be a critical early messenger governing revascularization in the
      setting of acute vascular occlusions. METHODS: C57 BL/6 mice deficient in the
      Egr1 gene (knockout) and their wild-type litter mates underwent ligation and
      excision of the femoral artery with or without the previous administration of 2.7
      x 10(9) particle units of an adenoviral vector coding for the vascular
      endothelial growth factor gene (VEGF) or Egr1. Distal hind limb perfusion was
      serially measured in these animals with laser Doppler perfusion imaging. RESULTS:
      Wild-type mice (n = 9) had nearly complete restitution of hind limb perfusion by
      day 35 after ligation. In contrast, all noninjected Egr1 knockout mice (n = 5)
      had severe ipsilateral limb necrosis develop between 1 and 4 days after ligation
      (P <.0001). Egr1 knockout mice injected with VEGF vector (n = 4) demonstrated
      significantly improved perfusion relative to baseline by postligation day 28,
      which persisted to postligation day 35 (P <.05). Egr1 knockout animals injected
      with Egr1 vector (n = 7) demonstrated a partial recovery of hind limb perfusion
      relative to VEGF vector-treated knockout animals at postligation day 4 (P <.01),
      which persisted to day 35. CONCLUSIONS: These findings suggest that early growth
      response 1 plays a pivotal role in reperfusion responses to vascular occlusion in
      mice and possibly other mammals.

PMID- 15457162
TI  - Reduction of myocardial reperfusion injury by aprotinin after regional ischemia
      and cardioplegic arrest.
AB  - BACKGROUND: Surgical coronary revascularization with cardiopulmonary bypass and
      cardioplegia has been associated with reperfusion injury. The serine protease
      inhibitor aprotinin has been suggested to reduce reperfusion injury, yet a
      clinically relevant study examining regional ischemia under conditions of
      cardiopulmonary bypass and cardioplegia has not been performed. METHODS: Pigs
      were subjected to 30 minutes of regional myocardial ischemia by distal left
      anterior descending coronary artery occlusion, followed by 60 minutes of
      cardiopulmonary bypass with 45 minutes of cardioplegic arrest and 90 minutes of
      post-cardiopulmonary bypass reperfusion. The treatment group (n = 6) was
      administered aprotinin systemically (40,000 kallikrein-inhibiting units [KIU]/kg
      intravenous loading dose, 40,000 KIU/kg pump prime, and 10,000 KIU x kg(-1) x h(
      1) intravenous continuous infusion). Control animals (n = 6) received crystalloid
      solution. Global and regional myocardial functions were analyzed by the left
      ventricular+dP/dt and the percentage segment shortening, respectively. Left
      ventricular infarct size was measured by tetrazolium staining. Tissue
      myeloperoxidase activity was measured. Myocardial sections were
      immunohistochemically stained for nitrotyrosine. Coronary microvessel function
      was studied by videomicroscopy. RESULTS: Myocardial infarct size was decreased
      with aprotinin treatment (27.0% +/- 3.5% vs 45.3% +/- 3.0%, aprotinin vs control;
      P <.05). Myocardium from the ischemic territory showed diminished nitrotyrosine
      staining in aprotinin-treated animals versus controls, and this was significant
      by grade (1.3 +/- 0.2 vs 3.2 +/- 0.2, aprotinin vs control; P <.01). In the
      aprotinin group, coronary microvessel relaxation improved most in response to the
      endothelium-dependent agonist adenosine diphosphate (44.7% +/- 3.2% vs 19.7% +/-
      1.7%, aprotinin vs control; P <.01). No significant improvements in myocardial
      function were observed with aprotinin treatment. CONCLUSIONS: Aprotinin reduces
      reperfusion injury after regional ischemia and cardioplegic arrest. Protease
      inhibition may represent a molecular strategy to prevent postoperative myocardial
      injury after surgical revascularization with cardiopulmonary bypass.

PMID- 15457163
TI  - Effects of hydrostatic distention on in vitro vasoreactivity of radial artery
      conduits.
AB  - BACKGROUND: Surgical preparation of coronary conduits may affect early and long
      term patency through endothelial and smooth muscle injury. We investigated the
      effect of hydrostatic distention on the in vitro endothelial function and
      contractile properties of the human radial artery. METHODS: Human radial arteries
      were harvested and distended to physiologic pressure or suprasystemic pressure
      (>300 mm Hg) by using heparinized whole blood for 2 minutes. Distal segments were
      retrieved and prepared into 3-mm rings. These were mounted and stretched to
      optimum resting tension in oxygenated Krebs solution at 37 degrees C. Contraction
      responses to potassium, norepinephrine, and serotonin and relaxation responses to
      acetylcholine and nitroprusside were evaluated. Undistended radial artery
      segments were used as controls. RESULTS: Vasocontraction to all 3 contractile
      agonists was significantly different between groups. The radial artery subjected
      to suprasystemic pressure distention achieved the lowest percentage of maximum
      contraction (potassium, P <.001; norepinephrine, P <.05; serotonin, P <.05). The
      median effective concentration was also significantly reduced in this group,
      indicating increased sensitivity to all 3 agonists. Receptor-mediated
      contractility was significantly reduced in both distended groups when compared
      with controls. Relaxation to acetylcholine and nitroprusside was significantly
      reduced in the suprasystemic pressure-distended group, which had a tendency to
      vasospasm when exposed to a physiologic concentration of acetylcholine (10(-6)
      mol/L). Median effective concentrations for both acetylcholine and nitroprusside
      were not different between groups. CONCLUSIONS: Excessive distention of the
      radial artery leads to a significant reduction in vasoreactivity, which may be
      attributed to a disruption of the vascular endothelium and media, with a
      propensity for graft spasm with exposure to acetylcholine.

PMID- 15457164
TI  - Malignant peripheral nerve sheath tumor of the mediastinum: a temporary aortic
      transection approach.

PMID- 15457165
TI  - Twisting of pedicled left internal thoracic artery graft three hundred sixty
      degrees clockwise: does it change the outcome?

PMID- 15457166
TI  - HeartMate XVE malfunction caused by fluid aspiration into the vent port.

PMID- 15457167
TI  - Surgical management of bilateral multiple invasive pulmonary aspergillosis.

PMID- 15457168
TI  - Rigid-plate fixation for the treatment of sternal nonunion.

PMID- 15457169
TI  - Biventricular assistance with the Jarvik FlowMaker: a case report.

PMID- 15457170
TI  - Nesiritide as an adjunctive therapy in adult patients with heart failure
      undergoing high-risk cardiac surgery.

PMID- 15457171
TI  - Transit-time flow measurement cannot detect wrong anastomosis of an internal
      thoracic artery with the cardiac vein in coronary artery surgery.

PMID- 15457172
TI  - Acromegaly caused by ectopic growth hormone-releasing hormone secretion by a
      carcinoid bronchial tumor: a rare entity.

PMID- 15457173
TI  - Innominate artery transection in the setting of a bovine arch.

PMID- 15457174
TI  - Distal aortic arch aneurysm after endovascular stent graft repair for type B
      chronic aortic dissection.

PMID- 15457175
TI  - Venous embolization during sternotomy in children undergoing corrective heart
      surgery.

PMID- 15457176
TI  - First human transplantation of a bioengineered airway tissue.

PMID- 15457177
TI  - Two-conduit repair for anomalous origin of the left coronary artery from the
      pulmonary artery in an adult.

PMID- 15457178
TI  - Use of the AbioCor replacement heart as destination therapy for end-stage heart
      failure with irreversible pulmonary hypertension.

PMID- 15457179
TI  - Successful bilateral lung volume reduction in a child with emphysema from
      bronchiolitis obliterans.

PMID- 15457180
TI  - Gfi-1 restricts proliferation and preserves functional integrity of
      haematopoietic stem cells.
AB  - Haematopoietic stem cells (HSCs) sustain blood production throughout life. HSCs
      are capable of extensive proliferative expansion, as a single HSC may
      reconstitute lethally irradiated hosts. In steady-state, HSCs remain largely
      quiescent and self-renew at a constant low rate, forestalling their exhaustion
      during adult life. Whereas nuclear regulatory factors promoting proliferative
      programmes of HSCs in vivo and ex vivo have been identified, transcription
      factors restricting their cycling have remained elusive. Here we report that the
      zinc-finger repressor Gfi-1 (growth factor independent 1), a cooperating oncogene
      in lymphoid cells, unexpectedly restricts proliferation of HSCs. After loss of
      Gfi-1, HSCs display elevated proliferation rates as assessed by 5
      bromodeoxyuridine incorporation and cell-cycle analysis. Gfi-1-/- HSCs are
      functionally compromised in competitive repopulation and serial transplantation
      assays, and are rapidly out-competed in the bone marrow of mouse chimaeras
      generated with Gfi-1-/- embryonic stem cells. Thus, Gfi-1 is essential to
      restrict HSC proliferation and to preserve HSC functional integrity.

PMID- 15457181
TI  - Inhibitor of apoptosis proteins: new therapeutic targets in hematological cancer?
AB  - Apoptosis is an essential process for the selection and survival of lymphocytes.
      Resistance to apoptosis can promote malignant transformation of hematopoietic
      cells. Proteins that regulate apoptosis may therefore be critically involved in
      the development of hematological cancer. A delicate balance between pro- and
      antiapoptotic mechanisms determines whether a cell death signal can activate the
      execution of the apoptotic cell death program. The family of inhibitor of
      apoptosis (IAP) proteins is a recently identified, novel category of apoptosis
      regulatory proteins. IAPs can inhibit the activation of caspases that are the
      executioners of apoptosis, activated by both the extrinsic and intrinsic pathway.
      IAPs may thereby set the threshold for apoptosis-activation and play a key role
      in the regulation of apoptotic cell death. IAPs themselves are also subject to
      strict regulation through feedback mechanisms. This paper focuses on the role of
      IAP family proteins in the regulation of apoptosis and discusses implications for
      their involvement in cancer and possible use for cancer therapy, especially in
      leukemias and lymphomas.

PMID- 15457182
TI  - Regulation of hematopoietic stem cell growth.
AB  - Hematopoietic stem cells (HSC) must balance self-renewal and differentiation to
      provide sufficient primitive cells to sustain hematopoiesis, while generating
      more mature cells with specialized capabilities. The enhanced self-renewal
      capacity of primitive HSCs enables their ability to sustain hematopoiesis
      throughout decades of life and their ability to repopulate a host when used
      therapeutically in bone marrow transplantation. However, hematopoietic cell
      perturbations resulting in unchecked self-renewal participate in leukemogenesis.
      While mechanisms governing self-renewal are still being uncovered, they are
      thought to bear relationship to the malignant process in a variety of tumor types
      and may therefore provide useful therapeutic targets in putative cancer stem
      cells. This review discusses molecular mechanisms recently defined to participate
      in HSC governance and highlights features of stem cell interactions with the
      microenvironment that may help guide therapies directed at HSCs.

PMID- 15457183
TI  - The GSTT1 deletion polymorphism is associated with initial response to
      glucocorticoids in childhood acute lymphoblastic leukemia.

PMID- 15457184
TI  - Purified donor NK-lymphocyte infusion to consolidate engraftment after
      haploidentical stem cell transplantation.
AB  - This pilot study tested feasibility of natural killer cell purification and
      infusion (NK-DLI) in patients after haploidentical hematopoietic stem cell
      transplantation (HSCT). The aim was to obtain >or=1.0 x 10(7)/kg CD56+/CD3- NK
      cells and <1.0 x 10(5)/kg CD3+ T cells. Mononuclear cells were collected by 10 l
      leukapheresis. A two-step ex vivo procedure was used to purify NK cells, using an
      immunomagnetic T-cell depletion, followed by NK-cell enrichment. Five patients
      with high-risk myeloid malignancies were included, presenting 3-12 months after a
      haploidentical HSCT with mixed chimerism (3), impending graft failure (1) or
      early relapse (1). The purified product contained a median of 1.61 x 10(7)/kg
      (range 0.21-2.2) NK cells and 0.29 x 10(5)/kg (0.11-1.1) T cells. A purity of NK
      cells of 97% (78-99), a recovery of 35.5% (13-75), and a T-cell depletion of 3.55
      log (2.9-4.5) was achieved. Infusions were well tolerated and none of the
      patients developed graft-versus-host disease. We observed an increase in donor
      chimerism in 2/5, stable mixed chimerism, decreasing chimerism and relapse of AML
      in one patient each. Selection of NK-DLI is technically feasible. NK cells are
      well tolerated when used as adoptive immunotherapy in recipients of
      haploidentical HSCT.

PMID- 15457185
TI  - Another step forward towards improved outcome after HLA-haploidentical stem cell
      transplantation.

PMID- 15457186
TI  - Restoration of SHIP activity in a human leukemia cell line downregulates
      constitutively activated phosphatidylinositol 3-kinase/Akt/GSK-3beta signaling
      and leads to an increased transit time through the G1 phase of the cell cycle.
AB  - The inositol 5-phosphatase SHIP (SHIP-1) is a negative regulator of signal
      transduction in hematopoietic cells and targeted disruption of SHIP in mice leads
      to a myeloproliferative disorder. We analyzed the effects of SHIP on the human
      leukemia cell line Jurkat in which expression of endogenous SHIP protein is not
      detectable. Restoration of SHIP expression in Jurkat cells with an inducible
      expression system caused a 69% reduction of phosphatidylinositol 3,4,5
      trisphosphate (PtdIns(3,4,5)P(3)) and a 65% reduction of Akt kinase activity,
      which was associated with reduced phosphorylation of glycogen synthase kinase
      3beta (GSK-3beta) (Ser-9) without changing the phosphorylation of Bad (Ser-136),
      FKHR (Ser-256) or MAPK (Thr-202/Tyr-204). SHIP-expressing Jurkat cells showed an
      increased transit time through the G1 phase of the cell cycle, but SHIP did not
      cause a complete cell cycle arrest or apoptosis. Extension of the G1 phase was
      associated with an increased stability of the cell cycle inhibitor p27(Kip1) and
      reduced phosphorylation of the retinoblastoma protein Rb at serine residue 780.
      Our data indicate that restoration of SHIP activity in a human leukemia cell
      line, which has lost expression of endogenous SHIP, downregulates constitutively
      activated phosphatidylinositol 3-kinase/Akt/GSK-3beta signaling and leads to an
      increased transit time through the G1 phase of the cell cycle.

PMID- 15457187
TI  - Raji revisited: cytogenetics of the original Burkitt's lymphoma cell line.

PMID- 15457188
TI  - Share the knowledge.

PMID- 15457193
TI  - British government releases plan to protect scientists and industry from animal
      rights extremists.

PMID- 15457194
TI  - PI and vet: potential conflict of interest?

PMID- 15457195
TI  - PI and vet: potential conflict of interest? PI can't go it alone.

PMID- 15457196
TI  - PI and vet: potential conflict of interest? Definite potential for conflict of
      interest.

PMID- 15457197
TI  - PI and vet: potential conflict of interest? PI can't act as AV.

PMID- 15457198
TI  - Head tilt and sudden blindness in a dog.

PMID- 15457200
TI  - The importance of understanding the natural history of novel species used in
      research.
AB  - Husbandry requirements differ greatly between species and failure to meet
      specific needs can result in widespread morbidity and mortality in populations of
      laboratory animals; this may be especially true in colonies of exotic animals.
      The author stresses the need to consider a species' natural history in providing
      housing and care in a research setting.

PMID- 15457201
TI  - An introduction to the Mexican axolotl (Ambystoma mexicanum).
AB  - A number of unusual traits, including a remarkable capacity for wound healing and
      limb regeneration, make the axolotl an interesting animal model. The author
      provides an overview of axolotl care and use in biomedical research.

PMID- 15457202
TI  - The ferret: an animal model to study influenza virus.
AB  - There has been much critical influenza research conducted in a little-known
      laboratory animal--the ferret. The authors review some of these findings, discuss
      the reasons the ferret often becomes a model for influenza infection, and compare
      the ferret with other animal models.

PMID- 15457203
TI  - The Nile grass rat as a laboratory animal.
AB  - Rodents are the subjects of the overwhelming majority of laboratory animal
      studies, and most laboratory rodents are nocturnal. The availability of a
      suitable diurnal rodent would provide a more effective animal model for
      biomedical research applicable to humans. The author describes several
      characteristics of the Nile grass rat that make this diurnal murid rodent an
      attractive laboratory animal.

PMID- 15457204
TI  - Echocardiographic changes in patients with malignant phase hypertension: the West
      Birmingham Malignant Hypertension Register.
AB  - In order to study the echocardiographic abnormalities in consecutive patients
      with malignant phase hypertension (MHT), we reviewed echocardiograms of 31
      patients (23 male; mean age 52+/-14 years) with MHT who were admitted to our
      unit. Trans-thoracic echocardiography was carried out in all patients, and
      echocardiographic measurements were compared with those of 39 patients (30 male;
      mean age 54+/-10 years) with controlled nonmalignant essential hypertension, and
      32 (19 male; mean age 51+/-10 years) healthy normotensive volunteers. Patients
      with MHT had a significantly higher mean systolic and diastolic blood pressure
      (P<0.001) compared to the other two groups. MHT patients had significantly
      greater mean left atrial dimensions (P=0.002), as well as aortic root dimensions
      (P=0.01) and left ventricular (LV) dimensions (with the exception of the
      diastolic internal diameter) (P<0.001). MHT patients also had a mean larger LV
      mass and LV mass index (both P<0.001) when compared to the other two groups. The
      mean ejection fraction was also lower in the MHT group (P<0.001). In conclusion,
      patients with MHT have significant cardiac hypertrophy, in association with
      systolic dysfunction and dilated left atria, irrespective of the duration of
      known hypertension. These abnormalities may predispose MHT patients to
      cardiovascular complications including heart failure and cardiac arrhythmias,
      such as atrial fibrillation.

PMID- 15457205
TI  - Treatment of systolic hypertension: spotlight on recent studies with angiotensin
      II antagonists.
AB  - Systolic blood pressure has a continuous, graded, strong, independent, and
      aetiologically significant relationship to mortality from coronary heart disease,
      stroke, and all cardiovascular diseases, as well as to all-cause mortality and
      life expectancy. Angiotensin II (AII) may be intimately involved in the
      pathogenesis of systolic hypertension through multiple mechanisms, including
      decreasing the elastin content and increasing the collagen content of the
      arterial wall, thickening and fibrotic remodelling of the vascular intima, and
      proliferating smooth muscle cells in the arterial wall, resulting in increased
      thickness, stiffening, and partial loss of contractility. AII antagonists may
      therefore offer hitherto unrecognized benefits (independent of blood pressure) on
      age-related vascular damage and provide particular benefits in patients with
      systolic hypertension. Recent evidence has demonstrated that losartan offers
      cardiovascular outcomes benefits in isolated systolic hypertension (ISH)
      associated with an excellent tolerability profile. This, in patients with ISH,
      AII antagonists more facilitate systolic BP control, providing cardiovascular
      protection and offering an excellent risk-benefit profile.

PMID- 15457206
TI  - Rationale and design of a study comparing two fixed-dose combination regimens to
      reduce albuminuria in patients with type II diabetes and hypertension.
AB  - Diabetic nephropathy is the leading cause of end-stage renal disease (ESRD). The
      early stage of nephropathy is manifested by the presence of low levels of urinary
      albumin (microalbuminuria or urinary albumin excretion >or=30 and <299 mg/day).
      Albuminuria is a marker for development of nephropathy in type II diabetes and
      for increased cardiovascular morbidity and mortality. Recent studies have
      demonstrated the importance of antihypertensive agents that inhibit the renin
      angiotensin-aldosterone (RAA) system to reduce the risk and slow down the
      progression of renal disease. A new clinical trial, GUARD (Gauging Albuminuria
      Reduction With Lotrel in Diabetic Patients With Hypertension), is designed to
      compare the change in urinary albumin to creatinine ratio after 1 year of initial
      treatment with either amlodipine besylate/benazepril HCl or benazepril
      HCl/hydrochlorothiazide. Other objectives include a comparison of the proportion
      of patients who progress to overt diabetic nephropathy and the safety of these
      two combination therapies in these high-risk patients.

PMID- 15457207
TI  - Structural insights into the regulation of PDK1 by phosphoinositides and inositol
      phosphates.
AB  - 3-phosphoinositide-dependent protein kinase-1 (PDK1) phosphorylates and activates
      many kinases belonging to the AGC subfamily. PDK1 possesses a C-terminal
      pleckstrin homology (PH) domain that interacts with PtdIns(3,4,5)P3/PtdIns(3,4)P2
      and with lower affinity to PtdIns(4,5)P2. We describe the crystal structure of
      the PDK1 PH domain, in the absence and presence of PtdIns(3,4,5)P3 and
      Ins(1,3,4,5)P4. The structures reveal a 'budded' PH domain fold, possessing an N
      terminal extension forming an integral part of the overall fold, and display an
      unusually spacious ligand-binding site. Mutagenesis and lipid-binding studies
      were used to define the contribution of residues involved in phosphoinositide
      binding. Using a novel quantitative binding assay, we found that Ins(1,3,4,5,6)P5
      and InsP6, which are present at micromolar levels in the cytosol, interact with
      full-length PDK1 with nanomolar affinities. Utilising the isolated PDK1 PH
      domain, which has reduced affinity for Ins(1,3,4,5,6)P5/InsP6, we perform
      localisation studies that suggest that these inositol phosphates serve to anchor
      a portion of cellular PDK1 in the cytosol, where it could activate its substrates
      such as p70 S6-kinase and p90 ribosomal S6 kinase that do not interact with
      phosphoinositides.

PMID- 15457208
TI  - ACF1 improves the effectiveness of nucleosome mobilization by ISWI through PHD
      histone contacts.
AB  - The nucleosome remodelling ATPase ISWI resides in several distinct protein
      complexes whose subunit composition reflects their functional specialization.
      Association of ISWI with ACF1, the largest subunit of CHRAC and ACF complexes,
      improves the efficiency of ISWI-induced nucleosome mobilization by an order of
      magnitude and also modulates the reaction qualitatively. In order to understand
      the principle by which ACF1 improves the efficiency of ISWI, we mapped their
      mutual interaction requirements and generated a series of ACF complexes lacking
      conserved ACF1 domains. Deletion of the C-terminal PHD finger modules of ACF1 or
      their disruption by zinc chelation profoundly affected the nucleosome
      mobilization capability of associated ISWI in trans. Interactions of the PHD
      fingers with the central domains of core histones contribute significantly to the
      binding of ACF to the nucleosome substrate, suggesting a novel role for PHD
      modules as nucleosome interaction determinants. Connecting ACF to histones may be
      prerequisite for efficient conversion of ATP-dependent conformational changes of
      ISWI into translocation of DNA relative to the histones during nucleosome
      mobilization.

PMID- 15457209
TI  - Crystal structure of human GGA1 GAT domain complexed with the GAT-binding domain
      of Rabaptin5.
AB  - GGA proteins coordinate the intracellular trafficking of clathrin-coated vesicles
      through their interaction with several other proteins. The GAT domain of GGA
      proteins interacts with ARF, ubiquitin, and Rabaptin5. The GGA-Rabaptin5
      interaction is believed to function in the fusion of trans-Golgi-derived vesicles
      to endosomes. We determined the crystal structure of a human GGA1 GAT domain
      fragment in complex with the Rabaptin5 GAT-binding domain. In this structure, the
      Rabaptin5 domain is a 90-residue-long helix. At the N-terminal end, it forms a
      parallel coiled-coil homodimer, which binds one GAT domain of GGA1. In the C
      terminal region, it further assembles into a four-helix bundle tetramer. The
      Rabaptin5-binding motif of the GGA1 GAT domain consists of a three-helix bundle.
      Thus, the binding between Rabaptin5 and GGA1 GAT domain is based on a helix
      bundle-helix bundle interaction. The current structural observation is consistent
      with previously reported mutagenesis data, and its biological relevance is
      further confirmed by new mutagenesis studies and affinity analysis. The four
      helix bundle structure of Rabaptin5 suggests a functional role in tethering
      organelles.

PMID- 15457210
TI  - RAGE potentiates Abeta-induced perturbation of neuronal function in transgenic
      mice.
AB  - Receptor for Advanced Glycation Endproducts (RAGE), a multiligand receptor in the
      immunoglobulin superfamily, functions as a signal-transducing cell surface
      acceptor for amyloid-beta peptide (Abeta). In view of increased neuronal
      expression of RAGE in Alzheimer's disease, a murine model was developed to assess
      the impact of RAGE in an Abeta-rich environment, employing transgenics (Tgs) with
      targeted neuronal overexpression of RAGE and mutant amyloid precursor protein
      (APP). Double Tgs (mutant APP (mAPP)/RAGE) displayed early abnormalities in
      spatial learning/memory, accompanied by altered activation of markers of synaptic
      plasticity and exaggerated neuropathologic findings, before such changes were
      found in mAPP mice. In contrast, Tg mice bearing a dominant-negative RAGE
      construct targeted to neurons crossed with mAPP animals displayed preservation of
      spatial learning/memory and diminished neuropathologic changes. These data
      indicate that RAGE is a cofactor for Abeta-induced neuronal perturbation in a
      model of Alzheimer's-type pathology, and suggest its potential as a therapeutic
      target to ameliorate cellular dysfunction.

PMID- 15457211
TI  - PVR plays a critical role via JNK activation in thorax closure during Drosophila
      metamorphosis.
AB  - PVR, the Drosophila homolog of the PDGF/VEGF receptor, has been implicated in
      border cell migration during oogenesis and hemocyte migration during
      embryogenesis. It was earlier shown that Mbc, a CDM family protein, and its
      effector, Rac, transduced the guidance signal from PVR during border cell
      migration. Here we demonstrate that PVR is also required for the morphogenetic
      process, thorax closure, during metamorphosis. The results of genetic and
      biochemical experiments indicate that PVR activates the JNK pathway. We present
      evidence showing Crk (an adaptor molecule), Mbc, ELMO (a homolog of
      Caenorhabditis elegans CED-12 and mammalian ELMO), and Rac to be mediators of JNK
      activation by PVR. In addition, we suppose that not only Rac but also Cdc42 is
      activated and involved in JNK activation downstream of PVR.

PMID- 15457212
TI  - GTP/GDP exchange by Sec12p enables COPII vesicle bud formation on synthetic
      liposomes.
AB  - The generation of COPII vesicles from synthetic liposome membranes requires the
      minimum coat components Sar1p, Sec23/24p, Sec13/31p, and a nonhydrolyzable GTP
      analog such as GMP-PNP. However, in the presence of GTP and the full complement
      of coat subunits, nucleotide hydrolysis by Sar1p renders the coat insufficiently
      stable to sustain vesicle budding. In order to recapitulate a more authentic, GTP
      dependent budding event, we introduced the Sar1p nucleotide exchange catalyst,
      Sec12p, and evaluated the dynamics of coat assembly and disassembly by light
      scattering and tryptophan fluorescence measurements. The catalytic, cytoplasmic
      domain of Sec12p (Sec12DeltaCp) activated Sar1p with a turnover 10-fold higher
      than the GAP activity of Sec23p stimulated by the full coat. COPII assembly was
      stabilized on liposomes incubated with Sec12DeltaCp and GTP. Numerous COPII
      budding profiles were visualized on membranes, whereas a parallel reaction
      conducted in the absence of Sec12DeltaCp produced no such profiles. We suggest
      that Sec12p participates actively in the growth of COPII vesicles by charging new
      Sar1p-GTP molecules that insert at the boundary between a bud and the surrounding
      endoplasmic reticulum membrane.

PMID- 15457213
TI  - Variable LH2 stoichiometry and core clustering in native membranes of
      Rhodospirillum photometricum.
AB  - The individual components of the photosynthetic unit (PSU), the light-harvesting
      complexes (LH2 and LH1) and the reaction center (RC), are structurally and
      functionally known in great detail. An important current challenge is the study
      of their assembly within native membranes. Here, we present AFM topographs at 12
      A resolution of native membranes containing all constituents of the PSU from
      Rhodospirillum photometricum. Besides the major technical advance represented by
      the acquisition of such highly resolved data of a complex membrane, the images
      give new insights into the organization of this energy generating apparatus in
      Rsp. photometricum: (i) there is a variable stoichiometry of LH2, (ii) the RC is
      completely encircled by a closed LH1 assembly, (iii) the LH1 assembly around the
      RC forms an ellipse, (iv) the PSU proteins cluster together segregating out of
      protein free lipid bilayers, (v) core complexes cluster although enough LH2 are
      present to prevent core-core contacts, and (vi) there is no cytochrome bc1
      complex visible in close proximity to the RCs. The functional significance of all
      these findings is discussed.

PMID- 15457214
TI  - Dual histone H3 methylation marks at lysines 9 and 27 required for interaction
      with CHROMOMETHYLASE3.
AB  - Both DNA methylation and post-translational histone modifications contribute to
      gene silencing, but the mechanistic relationship between these epigenetic marks
      is unclear. Mutations in two Arabidopsis genes, the KRYPTONITE (KYP) histone H3
      lysine 9 (H3K9) methyltransferase and the CHROMOMETHYLASE3 (CMT3) DNA
      methyltransferase, cause a reduction of CNG DNA methylation, suggesting that H3K9
      methylation controls CNG DNA methylation. Here we show that the chromodomain of
      CMT3 can directly interact with the N-terminal tail of histone H3, but only when
      it is simultaneously methylated at both the H3K9 and H3K27 positions.
      Furthermore, using chromatin immunoprecipitation analysis and
      immunohistolocalization experiments, we found that H3K27 methylation colocalizes
      with H3K9 methylation at CMT3-controlled loci. The H3K27 methylation present at
      heterochromatin was not affected by mutations in KYP or in several Arabidopsis
      PcG related genes including the Enhancer of Zeste homologs, suggesting that a
      novel pathway controls heterochromatic H3K27 methylation. Our results suggest a
      model in which H3K9 methylation by KYP, and H3K27 methylation by an unknown
      enzyme provide a combinatorial histone code for the recruitment of CMT3 to silent
      loci.

PMID- 15457215
TI  - The Rb tumor suppressor is required for stress erythropoiesis.
AB  - The retinoblastoma tumor suppressor gene plays important roles in cell cycle
      control, differentiation and survival during development and is functionally
      inactivated in most human cancers. Early studies using gene targeting in mice
      suggested a critical role for pRb in erythropoiesis, while more recent
      experiments have suggested that many of the abnormal embryonic phenotypes in the
      Rb null mouse result from a defective placenta. To address this controversy and
      determine whether Rb has cell intrinsic functions in erythropoiesis, we examined
      the effects of Rb loss on red cell production following acute deletion of pRb in
      vitro and under different stress conditions in vivo. Under stress conditions, pRb
      was required to regulate erythroblast expansion and promote red cell enucleation.
      Acute deletion of Rb in vitro induced erythroid cell cycle and differentiation
      defects similar to those observed in vivo. These results demonstrate a cell
      intrinsic role for pRb in stress erythropoiesis and hematopoietic homeostasis
      that has relevance for human diseases.

PMID- 15457217
TI  - Holding the line at NASA.

PMID- 15457218
TI  - Open-source biology.

PMID- 15457216
TI  - Evidence for distinct mechanisms facilitating transcript elongation through
      chromatin in vivo.
AB  - The mechanism and kinetics of RNA polymerase II transcription and histone
      acetylation were studied by chromatin immunoprecipitation in yeast. Our results
      indicate that a significant fraction of polymerases starting transcription never
      make it to the end of a long GAL-VPS13 fusion gene. Surprisingly, induction of
      GAL genes results in substantial loss of histone-DNA contacts not only in the
      promoter but also in the coding region. The loss of nucleosomes is dependent on
      active transcript elongation, but apparently occurs independently of histone
      acetylation. In contrast, histones in genes previously shown to require the
      histone acetyltransferases GCN5 and ELP3 for normal transcription do not lose DNA
      contacts, but do become acetylated as a result of transcription. Together, these
      results suggest the existence of at least two distinct mechanisms to achieve
      efficient transcript elongation through chromatin: a pathway based on loss of
      histone-DNA contacts, and a histone acetylation-dependent mechanism correlating
      with little or no net loss of nucleosomes.

PMID- 15457219
TI  - Global AIDS trial denied patients as US balks at generic drug use.

PMID- 15457220
TI  - Biologists launch 'open-source movement'.

PMID- 15457221
TI  - Support sought to investigate sluggish Pioneers.

PMID- 15457222
TI  - Monkey virus may be cleared of cancer link.

PMID- 15457223
TI  - Feathers fly as China cracks down on illegal fossil sales.

PMID- 15457225
TI  - Beagle cash dogged by dissent over wording.

PMID- 15457224
TI  - Ancient ships lifted from Naples' railway tunnels.

PMID- 15457226
TI  - NIH researchers face blanket consulting ban.

PMID- 15457228
TI  - Hormone therapy: a dangerous elixir?

PMID- 15457229
TI  - Aquaculture: fishing for trouble.

PMID- 15457230
TI  - Meyer case poses a challenge to the system.

PMID- 15457231
TI  - Meyer: disagreements but no misconduct.

PMID- 15457232
TI  - Consumer group replies to attack on organic food.

PMID- 15457233
TI  - Alert to a European epidemic.

PMID- 15457238
TI  - The domino effect.

PMID- 15457239
TI  - Accelerator physics: electrons hang ten on laser wake.

PMID- 15457240
TI  - Plant disease: underground life for rice foe.

PMID- 15457242
TI  - Global change: glacial pace picks up.

PMID- 15457241
TI  - Human evolution: pedigrees for all humanity.

PMID- 15457243
TI  - Cosmology: what is dark energy?

PMID- 15457244
TI  - Cell biology: sight at the end of the tunnel.

PMID- 15457246
TI  - Biogeochemistry: early options in photosynthesis.

PMID- 15457248
TI  - Athletics: momentous sprint at the 2156 Olympics?
AB  - The 2004 Olympic women's 100-metre sprint champion, Yuliya Nesterenko, is assured
      of fame and fortune. But we show here that--if current trends continue--it is the
      winner of the event in the 2156 Olympics whose name will be etched in sporting
      history forever, because this may be the first occasion on which the race is won
      in a faster time than the men's event.

PMID- 15457249
TI  - Lung cancer: intragenic ERBB2 kinase mutations in tumours.
AB  - The protein-kinase family is the most frequently mutated gene family found in
      human cancer and faulty kinase enzymes are being investigated as promising
      targets for the design of antitumour therapies. We have sequenced the gene
      encoding the transmembrane protein tyrosine kinase ERBB2 (also known as HER2 or
      Neu) from 120 primary lung tumours and identified 4% that have mutations within
      the kinase domain; in the adenocarcinoma subtype of lung cancer, 10% of cases had
      mutations. ERBB2 inhibitors, which have so far proved to be ineffective in
      treating lung cancer, should now be clinically re-evaluated in the specific
      subset of patients with lung cancer whose tumours carry ERBB2 mutations.

PMID- 15457250
TI  - A supernova origin for dust in a high-redshift quasar.
AB  - Interstellar dust plays a crucial role in the evolution of the Universe by
      assisting the formation of molecules, by triggering the formation of the first
      low-mass stars, and by absorbing stellar ultraviolet-optical light and
      subsequently re-emitting it at infrared/millimetre wavelengths. Dust is thought
      to be produced predominantly in the envelopes of evolved (age >1 Gyr), low-mass
      stars. This picture has, however, recently been brought into question by the
      discovery of large masses of dust in the host galaxies of quasars at redshift z >
      6, when the age of the Universe was less than 1 Gyr. Theoretical studies,
      corroborated by observations of nearby supernova remnants, have suggested that
      supernovae provide a fast and efficient dust formation environment in the early
      Universe. Here we report infrared observations of a quasar at redshift 6.2, which
      are used to obtain directly its dust extinction curve. We then show that such a
      curve is in excellent agreement with supernova dust models. This result
      demonstrates a supernova origin for dust in this high-redshift quasar, from which
      we infer that most of the dust at high redshifts probably has the same origin.

PMID- 15457251
TI  - Monoenergetic beams of relativistic electrons from intense laser-plasma
      interactions.
AB  - High-power lasers that fit into a university-scale laboratory can now reach
      focused intensities of more than 10(19) W cm(-2) at high repetition rates. Such
      lasers are capable of producing beams of energetic electrons, protons and gamma
      rays. Relativistic electrons are generated through the breaking of large
      amplitude relativistic plasma waves created in the wake of the laser pulse as it
      propagates through a plasma, or through a direct interaction between the laser
      field and the electrons in the plasma. However, the electron beams produced from
      previous laser-plasma experiments have a large energy spread, limiting their use
      for potential applications. Here we report high-resolution energy measurements of
      the electron beams produced from intense laser-plasma interactions, showing that-
      under particular plasma conditions--it is possible to generate beams of
      relativistic electrons with low divergence and a small energy spread (less than
      three per cent). The monoenergetic features were observed in the electron energy
      spectrum for plasma densities just above a threshold required for breaking of the
      plasma wave. These features were observed consistently in the electron spectrum,
      although the energy of the beam was observed to vary from shot to shot. If the
      issue of energy reproducibility can be addressed, it should be possible to
      generate ultrashort monoenergetic electron bunches of tunable energy, holding
      great promise for the future development of 'table-top' particle accelerators.

PMID- 15457252
TI  - High-quality electron beams from a laser wakefield accelerator using plasma
      channel guiding.
AB  - Laser-driven accelerators, in which particles are accelerated by the electric
      field of a plasma wave (the wakefield) driven by an intense laser, have
      demonstrated accelerating electric fields of hundreds of GV m(-1) (refs 1-3).
      These fields are thousands of times greater than those achievable in conventional
      radio-frequency accelerators, spurring interest in laser accelerators as compact
      next-generation sources of energetic electrons and radiation. To date, however,
      acceleration distances have been severely limited by the lack of a controllable
      method for extending the propagation distance of the focused laser pulse. The
      ensuing short acceleration distance results in low-energy beams with 100 per cent
      electron energy spread, which limits potential applications. Here we demonstrate
      a laser accelerator that produces electron beams with an energy spread of a few
      per cent, low emittance and increased energy (more than 10(9) electrons above 80
      MeV). Our technique involves the use of a preformed plasma density channel to
      guide a relativistically intense laser, resulting in a longer propagation
      distance. The results open the way for compact and tunable high-brightness
      sources of electrons and radiation.

PMID- 15457253
TI  - A laser-plasma accelerator producing monoenergetic electron beams.
AB  - Particle accelerators are used in a wide variety of fields, ranging from medicine
      and biology to high-energy physics. The accelerating fields in conventional
      accelerators are limited to a few tens of MeV m(-1), owing to material breakdown
      at the walls of the structure. Thus, the production of energetic particle beams
      currently requires large-scale accelerators and expensive infrastructures. Laser
      plasma accelerators have been proposed as a next generation of compact
      accelerators because of the huge electric fields they can sustain (>100 GeV m(
      1)). However, it has been difficult to use them efficiently for applications
      because they have produced poor-quality particle beams with large energy spreads,
      owing to a randomization of electrons in phase space. Here we demonstrate that
      this randomization can be suppressed and that the quality of the electron beams
      can be dramatically enhanced. Within a length of 3 mm, the laser drives a plasma
      bubble that traps and accelerates plasma electrons. The resulting electron beam
      is extremely collimated and quasi-monoenergetic, with a high charge of 0.5 nC at
      170 MeV.

PMID- 15457254
TI  - Reaction discovery enabled by DNA-templated synthesis and in vitro selection.
AB  - Current approaches to reaction discovery focus on one particular transformation.
      Typically, researchers choose substrates based on their predicted ability to
      serve as precursors for the target structure, then evaluate reaction conditions
      for their ability to effect product formation. This approach is ideal for
      addressing specific reactivity problems, but its focused nature might leave many
      areas of chemical reactivity unexplored. Here we report a reaction discovery
      approach that uses DNA-templated organic synthesis and in vitro selection to
      simultaneously evaluate many combinations of different substrates for bond
      forming reactions in a single solution. Watson-Crick base pairing controls the
      effective molarities of substrates tethered to DNA strands; bond-forming
      substrate combinations are then revealed using in vitro selection for bond
      formation, PCR amplification and DNA microarray analysis. Using this approach, we
      discovered an efficient and mild carbon-carbon bond-forming reaction that
      generates an enone from an alkyne and alkene using an inorganic palladium
      catalyst. Although this approach is restricted to conditions and catalysts that
      are at least partially compatible with DNA, we expect that its versatility and
      efficiency will enable the discovery of additional reactions between a wide range
      of substrates.

PMID- 15457255
TI  - Photosynthetic microbial mats in the 3,416-Myr-old ocean.
AB  - Recent re-evaluations of the geological record of the earliest life on Earth have
      led to the suggestion that some of the oldest putative microfossils and
      carbonaceous matter were formed through abiotic hydrothermal processes.
      Similarly, many early Archaean (more than 3,400-Myr-old) cherts have been
      reinterpreted as hydrothermal deposits rather than products of normal marine
      sedimentary processes. Here we present the results of a field, petrographic and
      geochemical study testing these hypotheses for the 3,416-Myr-old Buck Reef Chert,
      South Africa. From sedimentary structures and distributions of sand and mud, we
      infer that deposition occurred in normal open shallow to deep marine
      environments. The siderite enrichment that we observe in deep-water sediments is
      consistent with a stratified early ocean. We show that most carbonaceous matter
      was formed by photosynthetic mats within the euphotic zone and distributed as
      detrital matter by waves and currents to surrounding environments. We find no
      evidence that hydrothermal processes had any direct role in the deposition of
      either the carbonaceous matter or the enclosing sediments. Instead, we conclude
      that photosynthetic organisms had evolved and were living in a stratified ocean
      supersaturated in dissolved silica 3,416 Myr ago.

PMID- 15457256
TI  - Excitation of Earth's continuous free oscillations by atmosphere-ocean-seafloor
      coupling.
AB  - The Earth undergoes continuous oscillations, and free oscillation peaks have been
      consistently identified in seismic records in the frequency range 2-7 mHz (refs
      1, 2), on days without significant earthquakes. The level of daily excitation of
      this 'hum' is equivalent to that of magnitude 5.75 to 6.0 earthquakes, which
      cannot be explained by summing the contributions of small earthquakes. As slow or
      silent earthquakes have been ruled out as a source for the hum (except in a few
      isolated cases), turbulent motions in the atmosphere or processes in the oceans
      have been invoked as the excitation mechanism. We have developed an array-based
      method to detect and locate sources of the excitation of the hum. Our results
      demonstrate that the Earth's hum originates mainly in the northern Pacific Ocean
      during Northern Hemisphere winter, and in the Southern oceans during Southern
      Hemisphere winter. We conclude that the Earth's hum is generated by the
      interaction between atmosphere, ocean and sea floor, probably through the
      conversion of storm energy to oceanic infragravity waves that interact with
      seafloor topography.

PMID- 15457257
TI  - Two new carnivores from an unusual late Tertiary forest biota in eastern North
      America.
AB  - Late Cenozoic terrestrial fossil records of North America are biased by a
      predominance of mid-latitude deposits, mostly in the western half of the
      continent. Consequently, the biological history of eastern North America,
      including the eastern deciduous forest, remains largely hidden. Unfortunately,
      vertebrate fossil sites from this vast region are rare, and few pertain to the
      critically important late Tertiary period, during which intensified global
      climatic changes took place. Moreover, strong phylogenetic affinities between the
      flora of eastern North America and eastern Asia clearly demonstrate formerly
      contiguous connections, but disparity among shared genera (eastern Asia-eastern
      North America disjunction) implies significant periods of separation since at
      least the Miocene epoch. Lacustrine sediments deposited within a former sinkhole
      in the southern Appalachian Mountains provide a rare example of a late Miocene to
      early Pliocene terrestrial biota from a forested ecosystem. Here we show that the
      vertebrate remains contained within this deposit represent a unique combination
      of North American and Eurasian taxa. A new genus and species of the red (lesser)
      panda (Pristinailurus bristoli), the earliest and most primitive so far known,
      was recovered. Also among the fauna are a new species of Eurasian badger
      (Arctomeles dimolodontus) and the largest concentration of fossil tapirs ever
      recorded. Cladistical analyses of the two new carnivores strongly suggest
      immigration events that were earlier than and distinct from previous records, and
      that the close faunal affinities between eastern North America and eastern Asia
      in the late Tertiary period are consistent with the contemporaneous botanical
      record.

PMID- 15457258
TI  - New evidence on the earliest human presence at high northern latitudes in
      northeast Asia.
AB  - The timing of early human dispersal to Asia is a central issue in the study of
      human evolution. Excavations in predominantly lacustrine sediments at Majuangou,
      Nihewan basin, north China, uncovered four layers of indisputable hominin stone
      tools. Here we report magnetostratigraphic results that constrain the age of the
      four artefact layers to an interval of nearly 340,000 yr between the Olduvai
      subchron and the Cobb Mountain event. The lowest layer, about 1.66 million years
      old (Myr), provides the oldest record of stone-tool processing of animal tissues
      in east Asia. The highest layer, at about 1.32 Myr, correlates with the stone
      tool layer at Xiaochangliang, previously considered the oldest archaeological
      site in this region. The findings at Majuangou indicate that the oldest known
      human presence in northeast Asia at 40 degrees N is only slightly younger than
      that in western Asia. This result implies that a long yet rapid migration from
      Africa, possibly initiated during a phase of warm climate, enabled early human
      populations to inhabit northern latitudes of east Asia over a prolonged period.

PMID- 15457259
TI  - Modelling the recent common ancestry of all living humans.
AB  - If a common ancestor of all living humans is defined as an individual who is a
      genealogical ancestor of all present-day people, the most recent common ancestor
      (MRCA) for a randomly mating population would have lived in the very recent past.
      However, the random mating model ignores essential aspects of population
      substructure, such as the tendency of individuals to choose mates from the same
      social group, and the relative isolation of geographically separated groups. Here
      we show that recent common ancestors also emerge from two models incorporating
      substantial population substructure. One model, designed for simplicity and
      theoretical insight, yields explicit mathematical results through a probabilistic
      analysis. A more elaborate second model, designed to capture historical
      population dynamics in a more realistic way, is analysed computationally through
      Monte Carlo simulations. These analyses suggest that the genealogies of all
      living humans overlap in remarkable ways in the recent past. In particular, the
      MRCA of all present-day humans lived just a few thousand years ago in these
      models. Moreover, among all individuals living more than just a few thousand
      years earlier than the MRCA, each present-day human has exactly the same set of
      genealogical ancestors.

PMID- 15457260
TI  - Phenotypic consequences of 1,000 generations of selection at elevated CO2 in a
      green alga.
AB  - Estimates of the effect of increasing atmospheric CO2 concentrations on future
      global plant production rely on the physiological response of individual plants
      or plant communities when exposed to high CO2 (refs 1-6). Plant populations may
      adapt to the changing atmosphere, however, such that the evolved plant
      communities of the next century are likely to be genetically different from
      contemporary communities. The properties of these future communities are unknown,
      introducing a bias of unknown sign and magnitude into projections of global
      carbon pool dynamics. Here we report a long-term selection experiment to
      investigate the phenotypic consequences of selection for growth at elevated CO2
      concentrations. After about 1,000 generations, selection lines of the unicellular
      green alga Chlamydomonas failed to evolve specific adaptation to a CO2
      concentration of 1,050 parts per million. Some lines, however, evolved a syndrome
      involving high rates of photosynthesis and respiration, combined with higher
      chlorophyll content and reduced cell size. These lines also grew poorly at
      ambient concentrations of CO2. We tentatively attribute this outcome to the
      accumulation of conditionally neutral mutations in genes affecting the carbon
      concentration mechanism.

PMID- 15457261
TI  - Pack-MULE transposable elements mediate gene evolution in plants.
AB  - Mutator-like transposable elements (MULEs) are found in many eukaryotic genomes
      and are especially prevalent in higher plants. In maize, rice and Arabidopsis a
      few MULEs were shown to carry fragments of cellular genes. These chimaeric
      elements are called Pack-MULEs in this study. The abundance of MULEs in rice and
      the availability of most of the genome sequence permitted a systematic analysis
      of the prevalence and nature of Pack-MULEs in an entire genome. Here we report
      that there are over 3,000 Pack-MULEs in rice containing fragments derived from
      more than 1,000 cellular genes. Pack-MULEs frequently contain fragments from
      multiple chromosomal loci that are fused to form new open reading frames, some of
      which are expressed as chimaeric transcripts. About 5% of the Pack-MULEs are
      represented in collections of complementary DNA. Functional analysis of amino
      acid sequences and proteomic data indicate that some captured gene fragments
      might be functional. Comparison of the cellular genes and Pack-MULE counterparts
      indicates that fragments of genomic DNA have been captured, rearranged and
      amplified over millions of years. Given the abundance of Pack-MULEs in rice and
      the widespread occurrence of MULEs in all characterized plant genomes, gene
      fragment acquisition by Pack-MULEs might represent an important new mechanism for
      the evolution of genes in higher plants.

PMID- 15457262
TI  - Small modulation of ongoing cortical dynamics by sensory input during natural
      vision.
AB  - During vision, it is believed that neural activity in the primary visual cortex
      is predominantly driven by sensory input from the environment. However, visual
      cortical neurons respond to repeated presentations of the same stimulus with a
      high degree of variability. Although this variability has been considered to be
      noise owing to random spontaneous activity within the cortex, recent studies show
      that spontaneous activity has a highly coherent spatio-temporal structure. This
      raises the possibility that the pattern of this spontaneous activity may shape
      neural responses during natural viewing conditions to a larger extent than
      previously thought. Here, we examine the relationship between spontaneous
      activity and the response of primary visual cortical neurons to dynamic natural
      scene and random-noise film images in awake, freely viewing ferrets from the time
      of eye opening to maturity. The correspondence between evoked neural activity and
      the structure of the input signal was weak in young animals, but systematically
      improved with age. This improvement was linked to a shift in the dynamics of
      spontaneous activity. At all ages including the mature animal, correlations in
      spontaneous neural firing were only slightly modified by visual stimulation,
      irrespective of the sensory input. These results suggest that in both the
      developing and mature visual cortex, sensory evoked neural activity represents
      the modulation and triggering of ongoing circuit dynamics by input signals,
      rather than directly reflecting the structure of the input signal itself.

PMID- 15457263
TI  - A transmembrane protein required for acetylcholine receptor clustering in
      Caenorhabditis elegans.
AB  - Clustering neurotransmitter receptors at the synapse is crucial for efficient
      neurotransmission. Here we identify a Caenorhabditis elegans locus, lev-10,
      required for postsynaptic aggregation of ionotropic acetylcholine receptors
      (AChRs). lev-10 mutants were identified on the basis of weak resistance to the
      anthelminthic drug levamisole, a nematode-specific cholinergic agonist that
      activates AChRs present at neuromuscular junctions (NMJs) resulting in muscle
      hypercontraction and death at high concentrations. In lev-10 mutants, the density
      of levamisole-sensitive AChRs at NMJs is markedly reduced, yet the number of
      functional AChRs present at the muscle cell surface remains unchanged. LEV-10 is
      a transmembrane protein localized to cholinergic NMJs and required in body-wall
      muscles for AChR clustering. We also show that the LEV-10 extracellular region,
      containing five predicted CUB domains and one LDLa domain, is sufficient to
      rescue AChR aggregation in lev-10 mutants. This suggests a mechanism for AChR
      clustering that relies on extracellular protein-protein interactions. Such a
      mechanism is likely to be evolutionarily conserved because CUB/LDL transmembrane
      proteins similar to LEV-10, but lacking any assigned function, are expressed in
      the mammalian nervous system and might be used to cluster ionotropic receptors in
      vertebrates.

PMID- 15457264
TI  - The rice leaf blast pathogen undergoes developmental processes typical of root
      infecting fungi.
AB  - Pathogens have evolved different strategies to overcome the various barriers that
      they encounter during infection of their hosts. The rice blast fungus Magnaporthe
      grisea causes one of the most damaging diseases of cultivated rice and has
      emerged as a paradigm system for investigation of foliar pathogenicity. This
      fungus undergoes a series of well-defined developmental steps during leaf
      infection, including the formation of elaborate penetration structures
      (appressoria). This process has been studied in great detail, and over thirty M.
      grisea genes that condition leaf infection have been identified. Here we show a
      new facet of the M. grisea life cycle: this fungus can undergo a different (and
      previously uncharacterized) set of programmed developmental events that are
      typical of root-infecting pathogens. We also show that root colonization can lead
      to systemic invasion and the development of classical disease symptoms on the
      aerial parts of the plant. Gene-for-gene type specific disease resistance that is
      effective against rice blast in leaves also operates in roots. These findings
      have significant implications for fungal development, epidemiology, plant
      breeding and disease control.

PMID- 15457265
TI  - Structural basis for packaging the dimeric genome of Moloney murine leukaemia
      virus.
AB  - All retroviruses specifically package two copies of their genomes during virus
      assembly, a requirement for strand-transfer-mediated recombination during reverse
      transcription. Genomic RNA exists in virions as dimers, and the overlap of RNA
      elements that promote dimerization and encapsidation suggests that these
      processes may be coupled. Both processes are mediated by the nucleocapsid domain
      (NC) of the retroviral Gag polyprotein. Here we show that dimerization-induced
      register shifts in base pairing within the Psi-RNA packaging signal of Moloney
      murine leukaemia virus (MoMuLV) expose conserved UCUG elements that bind NC with
      high affinity (dissociation constant = 75 +/- 12 nM). These elements are base
      paired and do not bind NC in the monomeric RNA. The structure of the NC complex
      with a 101-nucleotide 'core encapsidation' segment of the MoMuLV Psi site reveals
      a network of interactions that promote sequence- and structure-specific binding
      by NC's single CCHC zinc knuckle. Our findings support a structural RNA switch
      mechanism for genome encapsidation, in which protein binding sites are
      sequestered by base pairing in the monomeric RNA and become exposed upon
      dimerization to promote packaging of a diploid genome.

PMID- 15457267
TI  - RNA interference: the silent treatment.

PMID- 15457271
TI  - Two-way traffic.

PMID- 15457273
TI  - Industry and interns. The intern experience.

PMID- 15457275
TI  - How does delaying treatment affect the long-term prognosis for patients with
      acute myocardial infarction treated with primary coronary angioplasty?
AB  - BACKGROUND: The benefit of thrombolysis in patients with acute myocardial
      infarction (AMI) strongly depends on the time from the onset of symptoms to the
      initiation of treatment. For AMI patients treated with percutaneous coronary
      interventions (PCI) this delay of treatment seems to be important only up to a
      certain time level. AIM: To assess the effects of time to treatment of AMI with
      PCI on the short- and long-term prognosis. METHODS: We followed 339 consecutive
      AMI patients treated with PCI from 1995 to 1999 in our centre. Patients were
      divided into five groups according to the time to treatment and ischaemic time
      (time from symptom onset to reperfusion). RESULTS: Time to treatment <90 min was
      achieved in 35 (10.5%) patients; 91-210 min in 105 (31%); 211-330 min in 72
      (21%); 331-690 min in 74 (22%); and >691 min in 53 (15.5%) patients. According to
      ischaemic time, the patients were divided into groups: <2 h, 2-4 h, 4-6 h, 6-12
      h, and >12 h. The ejection fraction of the left ventricle 3-5 days after AMI was
      50%, 51%, 45%, 40%, and 46%, and the 30 day mortality - 5.7%, 2.9%, 11.1%, 10.8%,
      and 11.3%, respectively. Compared with patients treated later, patients with time
      to treatment <3.5 h had a significantly higher rate of TIMI 3 flow (93.6% vs
      83.9%, p=0.007), lower 30-day mortality (3.6% vs 11.1%, p=0.012), lower 3-year
      mortality (8.6% vs 19.1%, p=0.003), lower frequency of heart failure during
      hospitalisation (11.4% vs 28.1%, p<0.001) as well as lower maximal level of
      creatine kinase (32+/-29 vs 44+/-39 micro kat/l, p=0.005). CONCLUSIONS: The
      success rate of primary PCI to achieve normal flow in an infarct-related artery
      is high, but it decreases when treatment is started later than 3,5 h from AMI
      onset. The short-term and long-term mortality as well as the incidence of heart
      failure during the acute phase of MI are the lowest when PCI is started within
      3,5 h from the onset of symptoms.

PMID- 15457276
TI  - Transcatheter closure of patent foramen ovale in patients with cryptogenic
      stroke.
AB  - BACKGROUND: Paradoxical embolism due to the presence of patent foramen ovale
      (PFO) is a well-established possible mechanism of ischaemic stroke of unknown
      origin. Mechanical sealing of the interatrial septum seems to be the most
      effective method for the prevention of stroke recurrences. AIM: To assess
      prospectively the short- and mid-term results of transcatheter closure of PFO in
      consecutive patients with a history of cryptogenic ischaemic stroke. METHODS:
      Between March 1999 and December 2002, thirty two patients with PFO (15 males, age
      from 19 to 55 years, mean 41 years) with a history of documented ischaemic stroke
      of unknown origin underwent transcatheter closure of PFO using an Amplatzer
      occluder. All procedures were performed under general anaesthesia and with
      transesophageal echocardiographic guidance. RESULTS: In all patients the
      procedure was effective and no complications were observed. During the follow-up
      period of a mean of 25.9 months (>12 months in 22 patients), no new neurological
      events were recorded. Control transesophageal echocardiography was performed in
      28 patients mean 22.3 months after the procedure and confirmed the correct
      positioning of the occluder. A significant (>30 bubbles of contrast) residual
      shunt was detected in two patients. One patient developed episodes of paroxysmal
      supraventricular tachycardia which were effectively cured by radiofrequency
      ablation. CONCLUSIONS: Transcatheter closure of PFO is safe, effective and devoid
      of side effects connected with extracorporeal circulation. This procedure may
      become the treatment of choice in patients with the highest risk of recurrent
      ischaemic stroke.

PMID- 15457277
TI  - Interaction between inflammation and thrombosis in acute coronary syndrome.
AB  - BACKGROUND: Inflammation and thrombosis are important in the pathogenesis of
      acute coronary syndrome (ACS). Cytokines [interleukin-1beta (IL-1beta) and
      interleukin-6 (IL-6)] are inflammation markers which play a major role in the
      development of coronary heart disease. Experimental data documented that an
      increase of cytokine and von Willebrand factor (vWF) levels in unstable angina
      (UA) and non-Q wave myocardial infarction (MI) predicts an adverse outcome. AIM:
      To examine the correlation between the IL-1beta, IL-6 and vWF levels in patients
      with ACS. METHODS: We examined 92 patients (74 men, 18 women, aged from 43 to 76)
      divided into 3 groups. The first group included 43 patients with a Q-wave MI, the
      second group - 33 with a non-Q-wave MI, and the third group - 18 with UA. All
      patients were given 125-250 mg of aspirin and bolus of 5.000 units of
      unfractionated heparin, followed by heparin infusion titrated to maintain an
      activated partial thromboplastin time of 50-75 s. Patients with a Q-wave MI
      received thrombolytic therapy 1.5 million units of streptokinase. The IL-1b, IL-6
      and vWF levels was measured on admission and 7 as well as 21 days later. Fifteen
      patients with stable angina served as the control group. RESULTS: The levels of
      cytokines and vWF were significantly higher in patients with ACS than in control
      subjects. A significant correlation between vWF and IL-6 levels, measured on
      admission and 7 days later, was found in patients with UA (r=+0.74 and r=+0.55,
      respectively). Also, a significant correlation was found between vWF and IL-1beta
      levels measured on admission in patients with either Q-wave or non-Q wave MI
      (r=+0.7 and r=+0.61, respectively). CONCLUSIONS: Our data suggest that there is a
      positive correlation between inflammation and thrombosis markers in patients with
      ACS.

PMID- 15457278
TI  - Prognostic value of troponin I after elective percutaneous coronary
      interventions.
AB  - BACKGROUND: A mild and asymptomatic increase in the troponin level following
      elective percutaneous coronary interventions (PCI) has been widely reported,
      however, the prognostic role of this finding has not yet been well
      established.Aim. To assess prognostic value of troponin I level increase
      following elective PCI. METHODS: The study group consisted of 90 consecutive
      patients who underwent elective PCI in our institution. Troponin I level (normal
      values <0.1 ug/L) was assessed at baseline and 12 as well as 24 hours after the
      procedure. In addition, CK-MB level was measured 12 and 24 hours following PCI.
      Left ventricular (LV) systolic performance was assessed echocardiographically at
      baseline and after 12 months. The incidence of major adverse coronary events
      (MACE) during one-year follow-up was also evaluated. RESULTS: An increase in
      troponin I level >0.1 ug/L was observed in 66 (73%) patients; of whom, 8 patients
      had a marked (>1.0 ug/L) increase of troponin I, with a concomitant significant
      elevation of the CK-MB level. Patients with a positive troponin test developed
      systolic LV abnormalities more often than patients with a normal troponin I level
      following PCI (p<0.001). There were 10 MACE in the troponin-positive group and 2
      in the troponin-negative patients (NS). Seven MACE occurred in patients with
      marked increase in troponin I level (>1.0 ug/L) which was significantly more
      often than in the troponin-negative patients (p<0.001). CONCLUSIONS: A mild
      increase in troponin I level following elective PCI was frequent and did not
      predict poor outcome, however, was associated with the development of LV systolic
      impairment. A marked (>1.0 ug/L) increase in troponin I level identified patients
      at risk of MACE. An increase in troponin I level was similar following various
      types of PCI.

PMID- 15457279
TI  - Cardiac rupture in acute myocardial infarction with ST segment elevation.
      Clinical course and prognosis.
AB  - INTRODUCTION: Cardiac rupture (CR), involving left ventricular free wall,
      interventricular septum or papillary muscles, accounts for 15% of all deaths in
      the acute phase of myocardial infarction (MI). After cardiac arrhythmias and
      cardiogenic shock, CR is the third most common cause of death in acute MI. In
      spite of progress in the treatment of MI, mortality due to CR did not change in
      recent years.Aim. To assess the incidence, clinical course and outcome in
      patients with acute MI complicated by CR who were treated in our centre. METHODS:
      The study group consisted of 697 consecutive patients who were hospitalised due
      to acute MI with ST segment elevation (STEMI). The in-hospital and three-month
      follow-up data were analysed in 27 (3.9%) patients who developed CR. In 20
      patients CR occurred in the left ventricular free wall, in 5 interventricular
      septum, in one both of these structures, and in one papillary muscle. The
      diagnosis of CR was based on clinical presentation and echocardiography. RESULTS:
      The overall mortality in 697 patients with STEMI was 10.5%. Mortality rate in
      patients with CR was 55.6% (15 patients) which accounted for 20.5% of all deaths.
      Nine patients with CR underwent cardiac surgery whereas 18 were treated
      conservatively. Two (22.2%) patients from the former group and 13 (72.2%)
      patients from the latter group died. CONCLUSIONS: 1. Mortality due to CR was
      increased in patients who were treated conservatively, who received thrombolysis
      and those who were females. 2. Rapid and accurate diagnosis, proper correction of
      hemodynamical disturbances and timely introduction of cardiac surgery improve
      prognosis in patients with CR complicating STEMI.

PMID- 15457280
TI  - Holter-type impedance cardiography device. A system for continuous and non
      invasive monitoring of cardiac haemodynamics.
AB  - Impedance cardiography (ICG) enables the non-invasive, reproducible, beat-to-beat
      estimation of stroke volume (SV) changes, and the measurement of the absolute
      values of the ejection time (ET) and pre-ejection period (PEP), which allows the
      indirect evaluation of cardiac contractility. The miniaturised, Holter-type
      impedance cardiography device with built-in one channel of ECG called ReoMonitor,
      was constructed. The system allows the long-term, beat-to-beat, automatic
      evaluation of SV, ET, PEP and heart rate. The measurements obtained by ReoMonitor
      were verified using on echocardiographic method in supine and tilted positions. A
      high correlation coefficient (r=0.83) was calculated between the measurements
      collected using both methods. Speech or vigorous movement distinctly lowered the
      percentage of properly recognised cardiac cycles (during daytime: 20-80%, during
      the night: 75-90%). However, during exercise testing on a cycloergometer the
      quality of recordings was good. The following clinical applications of a system
      are presented: a) evaluation of hemodynamical abnormalities caused by arrhythmia
      events, b) vasovagal syncope diagnosis, and c) optimisation of atrio-ventricular
      delay during dual-chamber pacing.

PMID- 15457281
TI  - [Myocardial infarction in patient with variant angina].
AB  - We present a case of a 49-year-old male with myocardial infarction in a course of
      variant angina. He was treated successfully with streptokinase, calcium
      antagonist and nitrates. Coronary angiography showed spasm of the left coronary
      artery, proximal spasm of the right coronary artery and myocardial bridging of
      the left anterior descending artery. He has been stable and symptom-free on a
      treatment with long acting calcium antagonist, nitrates and statin for 3-years.

PMID- 15457282
TI  - [Calcification of heart valves in hemodialized patients and their cardiosurgical
      correction].
AB  - Development of vascular and systemic calcification is one of the more serious and
      often occurring complications in hemodialyzed patients. The cardiac valves
      calcifications are of the essential importance. They are result of the very
      complicated calcification process connected with hyperphosphataemia,
      hyperparathyroidism, calcium carbonate administering and active vitamin D3
      metabolites as well as using dialysis fluids with high concentration of calcium.
      Elevated P and Ca x P product are both significant predictors of cardiovascular
      mortality in hemodialized patients. We describe two patients with cardiac failure
      because of cardiac valves calcification. Both patients underwent artificial
      valves implantation. The patients showed a marked improvement of the quality of
      life and haemodynamic status.

PMID- 15457283
TI  - [Calcifying valves and coronary atherosclerosis].

PMID- 15457285
TI  - [Angiogram of the month-myocardial infarction].

PMID- 15457286
TI  - [Electrocardiogram of the month].

PMID- 15457287
TI  - [Isolated pulmonary artery valvular stenosis and coronary artery disease in a 64
      year-old male].

PMID- 15457288
TI  - [Is radiofrequency ablation indicated in asymptomatic patients with WPW
      Syndrome?].

PMID- 15457289
TI  - [Obesity, insulin resistance and hyperglycemia in metabolic syndrome in females].

PMID- 15457292
TI  - Capsule endoscopy: new technology that is here to stay.

PMID- 15457293
TI  - Canadian Helicobacter Study Group Consensus Conference: Update on the management
      of Helicobacter pylori--an evidence-based evaluation of six topics relevant to
      clinical outcomes in patients evaluated for H pylori infection.
AB  - As an update to previously published recommendations for the management of
      Helicobacter pylori infection, an evidence-based appraisal of six topics was
      undertaken in a consensus conference sponsored by the Canadian Helicobacter Study
      Group. The issues addressed and recommendations made were: bismuth-containing
      quadruple therapy is appropriate as an alternative first-line eradication
      strategy for H pylori infection; searching for and treating H pylori infection is
      warranted in patients considered to be at high risk for gastric cancer; H pylori
      infection should be eradicated before initiating long-term treatment with
      nonsteroidal anti-inflammatory drugs or acetylsalicylic acid; the stool antigen
      test has a limited role in the diagnosis of H pylori infection; the benefits of H
      pylori eradication in patients on long-term proton pump inhibitor therapy are not
      sufficient to warrant recommending a strategy of searching for and eradicating
      the infection among these patients; and a strategy of "test and eradicate" for H
      pylori infection in patients with uninvestigated dyspepsia is cost-effective in
      Canada relative to a trial of proton pump inhibitor therapy. The goal was to
      establish guidelines on the best evidence using the same structure to address and
      formulate recommendations for each issue. The degree of consensus for each issue
      is presented.

PMID- 15457294
TI  - Capsule endoscopy: a single-centre experience with the first 226 capsules.
AB  - BACKGROUND: Capsule endoscopy (CE) refers to a novel diagnostic method of imaging
      the gastrointestinal tract using a wireless capsule that transmits images to a
      data recorder while the device traverses the small intestine. OBJECTIVE: To
      review the authors' experience with CE to determine the indications, outcomes and
      management of positive findings. METHODS: Patients were prepared for CE with a
      single dose of magnesium citrate. Following an 8 h fast, a sensor array system
      was applied to the abdomen, the capsule was swallowed and the images were
      transmitted to a data recorder worn on the patient's side. Typically, the battery
      life of the capsule is 8 h, following which the data recorder is returned,
      downloaded to a computer workstation and reviewed. RESULTS: To date, 226 capsule
      studies have been performed in 209 patients. The indications included obscure
      bleeding (167 studies: 88 overt, 79 occult), anemia (14 studies), evaluation for
      inflammatory bowel disease (12 studies), screening for polyps (10 studies), pain
      (19 studies) and abnormal radiological imaging (4 studies). In the setting of
      obscure bleeding, a definitive source of bleeding was discovered in 85 studies.
      This included angiodysplasia (52 studies), mitotic lesions (10 studies) and
      ulcers (23 studies). A probable source of bleeding was found in another 10
      capsule studies. In the setting of anemia without evidence of bleeding, the
      definitive findings included ulcers (three studies), angiodysplasia (two
      studies), mitotic lesions (one study) and celiac disease (one study). Of four
      patients with abnormal radiological imaging, CE demonstrated lesions in two. The
      results of 35 capsule studies led to laparotomy with curative surgical resection.
      In eight studies, the capsules became lodged within a stricture; none led to
      obstruction and three were managed endoscopically. CONCLUSION: The yield of CE in
      carefully selected patients with obscure bleeding approximates 51%. There appear
      to be few complications, and patient satisfaction appears high. Cost analysis and
      further studies of clinical outcomes are required to elucidate appropriate
      indications for this device.

PMID- 15457295
TI  - Wireless capsule endoscopy for obscure gastrointestinal bleeding: a single
      centre, one-year experience.
AB  - BACKGROUND: Wireless capsule endoscopy (CE) is increasingly being used in the
      investigation of obscure gastrointestinal (GI) bleeding, but some studies have
      found that many of the bleeding lesions recognized by this technique are within
      the reach of conventional endoscopy. METHODS: The results of CE performed in the
      authors' centre in a 12 month period for obscure GI bleeding were retrospectively
      reviewed. RESULTS: Of the 46 patients with obscure GI bleeding, CE found a
      definite or probable cause in 19 (41%) and a possible cause in another 10 (22%),
      with an overall diagnostic yield of 63%. One of these lesions was found to be
      within reach of conventional gastroscopy, two were within reach of push
      enteroscopy, four were within reach of colonoscopy and one was within reach of
      retrograde enteroscopy through a stoma. The percentage of patients with a
      bleeding source within reach of routine endoscopy but missed during pre-CE
      endoscopy was significantly higher for those patients having endoscopy only in
      the community (30% [eight of 27]) versus in the authors' centre (0% [zero of
      19]). CONCLUSIONS: CE was valuable for diagnosing bleeding lesions not only
      within the small bowel, but also in the stomach and colon. However, "second-look"
      endoscopy may be considered before ordering CE for obscure GI bleeding when local
      expertise is available.

PMID- 15457296
TI  - Description of prescribing practices in patients with upper gastrointestinal
      bleeding receiving intravenous proton pump inhibitors: a multicentre evaluation.
AB  - BACKGROUND: Intravenous forms of proton pump inhibitors (IV PPI) are routinely
      used for patients with acute upper gastrointestinal bleeding, but a significant
      concern for their inappropriate use has been suggested. patients and METHODS: All
      consecutive patients who received IV PPI (pantoprazole) over 20 months in six
      Canadian hospitals were reviewed. Prescribing practices, endoscopic findings and
      outcomes were recorded. RESULTS: A total of 854 patients received IV PPI. Over
      90% of patients were given IV PPI for treatment of known or suspected active
      upper gastrointestinal bleeding. Most patients (69%) underwent upper endoscopy,
      and 58% of these patients had peptic ulcer disease (PUD). The majority of
      patients who had endoscopy (57%) had IV PPI administered in advance of the
      procedure. Of the 334 patients who had IV PPI given in advance, 46 (13.8%) were
      found to have high risk bleeding PUD stigmata at endoscopy. The remaining 288
      patients (86.2%) with advance IV PPI had low-risk PUD lesions or non-PUD lesions;
      IV PPI was continued after endoscopy in 164 (56.9%) of these patients.
      CONCLUSIONS: IV PPI is often used before endoscopy in suspected upper
      gastrointestinal bleed and maintained, regardless of endoscopic findings, after
      the endoscopy in many Canadian centres. Further study is required to support
      these clinical practices.

PMID- 15457297
TI  - Endoscopic "antireflux" procedures: not yet ready for prime time.
AB  - Gastroesophageal reflux disease affects a significant portion of the North
      American population on a weekly and daily basis. Options, especially for erosive
      disease, involve long-term proton pump inhibitors or surgical fundoplication.
      More recently, a number of endoscopic antireflux techniques have been assessed.
      These fall into three broad categories: the Stretta (radiofrequency); endoscopic
      suturing and plication devices; and injectable bulking agents. In the present
      summary, the literature on these endoscopic techniques is critically reviewed,
      highlighting the unimpressive efficacy, potential and real complications, and the
      relevant methodological limitations of the studies. Although they are promising,
      it is clear that these procedures are still in a preliminary study phase and not
      ready for "prime time" clinical use.

PMID- 15457298
TI  - Endoscopic ultrasound findings in duodenal gangliocytic paraganglioma.
AB  - Gangliocytic paraganglioma is an uncommon benign neurogenic tumour of the
      digestive tract that is usually located in the descending duodenum. Due to the
      unusual location, such lesions are frequently overlooked on routine radiological
      examinations and initial endoscopy. With the recent development of endoscopic
      ultrasound, lesions in this location can be more easily detected and better
      viewed. A case of a duodenal gangliocytic paraglioma detected by endoscopic
      ultrasound is presented; this is possibly only the second such case to be
      reported in the literature.

PMID- 15457299
TI  - Canadian Association of Gastroenterology launches human resources planning
      initiatives.

PMID- 15457301
TI  - Due diligence.

PMID- 15457300
TI  - Gastrointestinal stromal tumours: etiology, pathology and clinical management.
AB  - Investigation of the regulation of cell growth, differentiation and death by
      signalling pathways has led to a greater understanding of how alterations in
      these pathways play a critical role in the development of some cancers, and has
      opened new opportunities for their treatment. In the present review, results with
      the prototype drug of this class, imatinib (Gleevec, Glivec [formerly STI571];
      Novartis, Switzerland), in metastatic gastrointestinal stromal tumours are
      presented. The present review originated from a conference of the authors held in
      Montreal, Quebec in June 2003, under the sponsorship of Novartis.

PMID- 15457302
TI  - The 2004 ACC/AHA Guidelines: a perspective and adaptation for Canada by the
      Canadian Cardiovascular Society Working Group.
AB  - Major changes in acute ST elevation myocardial infarction (STEMI) management
      prompted a comprehensive rewriting of the American College of Cardiology/American
      Heart Association Guidelines. The Canadian Cardiovascular Society (CCS)
      participated in both the writing process and the external review. Subsequently, a
      Canadian Working Group (CWG), formed under the auspices of the CCS, developed a
      perspective and adaptation for Canada. Herein, accounting for specific realities
      of the Canadian cardiovascular health system, is a discussion of the implications
      for prehospital care and transport, optimal reperfusion therapy and an approach
      to decision making regarding reperfusion options and invasive therapy following
      fibrinolytic therapy. Major recent developments regarding indications for
      implantable cardioverter defibrillator(s) (ICDs) also prompted a review of
      indications for ICDs and the optimal timing of implantation given the potential
      for recovery of left ventricular function. At least a 40-day, preferably a 12
      week, waiting period was judged to be optimal to evaluate left ventricular
      function post-STEMI. A recommended algorithm for the insertion of an ICD is
      provided. Implementation of the new STEMI guidelines has substantial implications
      for resources, organization and priorities of the Canadian health care system.
      While on the one hand, the necessary incremental funding to provide tertiary and
      quaternary care and to support revascularization and device implantation
      capability is desirable, it is equally or more important to develop enhanced
      prehospital care, including the capacity for early recognition, risk assessment,
      fibrinolytic therapy and/or triage to a tertiary care centre as part of an
      enlightened approach to improving cardiac care.

PMID- 15457303
TI  - Cardiac arrest care and emergency medical services in Canada.
AB  - BACKGROUND: Heart disease is the primary cause of mortality in Canada and
      survival to hospital discharge from out-of-hospital cardiac arrest is low.
      OBJECTIVE: To provide an overview of the outcomes for out-of-hospital cardiac
      arrest in Canada. METHODS: A national, descriptive, Utstein-style analysis of
      cardiac arrest care and emergency medical services was conducted. Data were
      compiled from five sources: the City of Edmonton Emergency Response Department,
      the British Columbia Ambulance Service, the Nova Scotia Emergency Health
      Services, the Urgences-sante corporation of the Montreal Metropolitan region and
      the Ontario Prehospital Advanced Life Support (OPALS) Study database. RESULTS:
      There were 5288 cardiac arrests from a range of small communities to large
      provincial cardiac arrest registries in 2002. They were men (62.6% to 70.1%) in
      their sixties and seventies, witnessed (35.2% to 55.0%), rarely receiving
      bystander cardiopulmonary resuscitation (CPR) (14.7% to 46.0%), often in asystole
      (35.7% to 51.3%), arresting at home (56.1%) and rarely surviving to hospital
      discharge (4.3% to 9.0%). Bystander CPR and early first responder defibrillation
      were significantly associated with increased survival. Cardiac arrest incidence
      rates per 100,000 varied between 53 and 59 among provinces and followed a
      downward trend. CONCLUSIONS: The results of this study could be an important
      first step toward a national cardiac arrest registry comparing the impact of
      regional differences in patient and system characteristics. Many communities do
      not have accurate data on their performance with regards to the chain of
      survival, or need to significantly improve their capacity for providing citizen
      bystander CPR and rapid first responder defibrillation.

PMID- 15457304
TI  - Accurate, simplified and rapid three-dimensional echocardiographic volume
      quantifications: Comparison of different algorithms in symmetric and asymmetric
      left ventricular geometry.
AB  - OBJECTIVE: A comparative investigation of dynamic three-dimensional freehand
      echocardiography (D3DFE) and magnetic resonance imaging (MRI) was conducted to
      determine the accuracy and rapidity of the average rotation method (ARM) and the
      disk summation method (DSM) for volumetric analysis. METHODS: In 15 patients with
      an asymmetric left ventricle and 12 normal subjects, end-diastolic and end
      systolic left ventricular volumes were assessed by D3DFE and by MRI. Both DSM and
      ARM were used for volume determination. All echocardiographic readings were
      performed by two examiners blinded to each other and to the MRI results. The
      times needed for echocardiographic data acquisition and volumetric analysis with
      either algorithm were determined. RESULTS: Correlation between ARM and MRI
      measurements was tighter than between DSM and MRI measurements (end-diastolic
      volume: r=0.95, P<0.0001 versus r=0.94, P<0.0001 in asymmetric ventricles; and
      r=0.97, P<0.0001 versus r=0.96, P<0.0001 in symmetric ventricles; end-systolic
      volume: r=0.94, P<0.0001 versus r=0.93, P<0.0001 in asymmetric ventricles and
      r=0.96, P<0.0001 versus r=0.94, P<0.0001 in symmetric ventricles). In addition,
      ARM analysis was less time-consuming than DSM (6.4+/-0.4 min versus 7.6+/-0.3
      min, P<0.05). CONCLUSIONS: For D3DFE, ARM is the most accurate and rapid approach
      to left ventricular volume determination. ARM benefits from advanced two
      dimensional imaging and can be easily added to any standard transthoracic
      echocardiographic examination.

PMID- 15457305
TI  - Increased pulse wave velocity and shortened pulse wave propagation time in young
      patients with rheumatoid arthritis.
AB  - BACKGROUND: Rheumatoid arthritis (RA) is a systemic immune and inflammatory
      disease associated with excess cardiovascular morbidity and mortality. Pulse wave
      velocity (PWV) is an index of arterial stiffness and a marker of cardiovascular
      events. OBJECTIVE: To investigate arterial stiffness using carotid-femoral
      (aortic) PWV measurements in young patients with RA. PATIENTS AND METHODS: Eight
      patients (aged 21 to 34 years, seven women, mean RA duration 13.8+/-12.6 months)
      with RA according to the criteria of the American College of Rheumatology, and
      eight age- and sex-matched control subjects (aged 22 to 34 years, seven women)
      were recruited. Aortic PWV was determined using an automatic device, the Complior
      (Complior Colson, France), which allowed on-line pulse wave recording and
      automatic calculation of PWV. RESULTS: The carotid-femoral PWV, systolic blood
      pressure and heart rate were higher in young patients with RA than in sex- and
      age-matched control subjects (P=0.03, P=0.02 and P=0.002, respectively). In the
      young patients with RA, pulse wave propagation time between measurement sites was
      significantly shorter than in the control group (P=0.02). There were no
      significant differences in the sex, age, body mass index, waist to hip ratio,
      diastolic blood pressure, mean blood pressure or pulse pressure between the two
      groups (P=1.00, P=0.71, P=0.20, P=0.66, P=0.55, P=0.07 and P=0.11, respectively).
      CONCLUSION: The carotid-femoral PWV is increased and pulse wave propagation time
      is decreased in young patients with RA. Measurements of carotid-femoral PWV may
      provide a simple and noninvasive technique for identifying patients at increased
      risk of vascular disease.

PMID- 15457306
TI  - Physician management preferences for cardiac patients: factors affecting referral
      to cardiac rehabilitation.
AB  - BACKGROUND: Cardiac rehabilitation (CR) is an evidence-based intervention that
      has been shown to reduce both morbidity and mortality. However, CR is widely
      underused due to multiple factors, including physician referral practices.
      OBJECTIVES: To describe physicians' preferences in managing cardiac patients and
      the barriers they face in referring patients to CR. METHODS: A cross-sectional
      survey of a stratified random sample of 510 primary care physicians,
      cardiologists and cardiovascular surgeons in Ontario was conducted. One hundred
      seventy-nine physicians responded (40% response rate through repeat mailings) to
      the survey that investigated medical, demographic and attitudinal factors
      affecting referral. A hypothetical case scenario that elicited open-ended factors
      affecting physician management preferences was incorporated. RESULTS: Physicians
      identified geographic access, uncertainty regarding which provider was
      responsible for referral and perceptions of patient motivation as important
      factors affecting referral to CR. Through principal components analysis, several
      attitudes affecting referral emerged, including beliefs about the efficacy of CR,
      referral norms, ease of the referral process and desire to manage the patient
      independently. A hierarchical logistic regression analysis showed that 75% of the
      variance in referral was attributable to medical specialty, availability of CR
      and practice norms. CONCLUSIONS: Increased communication among health care
      providers is needed to ensure CR referral. Due to geographic dispersion,
      alternatives to site-based CR are necessary to meet the needs of cardiac
      patients.

PMID- 15457307
TI  - Simple, quantitative body surface potential map parameters in the diagnosis of
      remote Q wave and non-Q wave myocardial infarction.
AB  - BACKGROUND: Body surface potential mapping has been shown to be a useful tool in
      the diagnosis and localization of remote non-Q wave and Q wave myocardial
      infarction, but human expertise is required to interpret the maps. OBJECTIVE: To
      identify quantitative body surface potential mapping parameters that could enable
      a computer-based diagnosis. METHODS: Body surface isopotential maps (63 unipolar
      leads) were recorded in 86 patients with remote Q wave and 71 patients with
      remote non-Q wave myocardial infarction. Twenty-four healthy adults served as
      control subjects. Myocardial infarctions were classified using standard
      electrocardiogram leads in the acute and chronic phases, and were validated by
      coronary angiography, ventriculography and thallium scintigraphy. RESULTS: Two
      simple quantitative parameters with high diagnostic power were identified: the
      time interval between the peak minimum and the peak maximum potentials (time
      shift), and the ratio of these potentials (maximum to minimum ratio [max/min]).
      Both parameters showed significant differences between infarction patients and
      normal control subjects, and optimum cut-off values were determined using
      receiver operating characteristic curves (anterior infarction: time-shift of -4
      ms or less, max/min of 0.6 or less; posterior infarction: time-shift of 8 ms or
      greater, max/min of 1.25 or greater). The sensitivities of the two parameters
      were 100% and 97%, and the specificities were 99% and 100%, respectively, in the
      anterior Q wave infarction group, compared with sensitivities of 88% and 100%,
      and specificities of 94% and 95%, respectively, in the posterior Q wave
      infarction group. In the anterior non-Q wave infarction group, sensitivity was
      35% for both parameters, specificity was 100% for both parameters, and only
      infarctions associated with a low ejection fraction were detected, indicating
      that infarction size may influence the power of the tests. CONCLUSIONS: Time
      shift and max/min are two new, simple, powerful parameters for infarction
      diagnosis and may also be suitable for automated, computer-based processing.

PMID- 15457308
TI  - A randomized trial of patient self-managed versus physician-managed oral
      anticoagulation.
AB  - BACKGROUND: Self-management (SM) of warfarin by patients is an attractive
      strategy, particularly if it improves anticoagulation control and can be done
      safely under minimal physician supervision. OBJECTIVE: To compare the effect of
      SM with physician-management (PM) on the maintenance of therapeutic
      anticoagulation. METHODS: A randomized, open-label eight-month trial was
      performed. Patients 18 years of age and older were eligible if they were
      receiving warfarin for at least one month before enrolment and required
      anticoagulation for at least one year to a target international normalized ratio
      (INR) of 2.0 to 3.0 or 2.5 to 3.5. Exclusion criteria were a known hypercoaguable
      disorder, mental incompetence, a language barrier or an inability to attend
      training sessions. Patients randomly assigned to SM tested their INR using a
      point-of-care device (Pro Time Microcogulation System, International Technidyne
      Corporation, USA) and adjusted their warfarin doses using a nomogram. Patients
      randomly assigned to PM received usual care from their general practitioner. The
      primary outcome was to demonstrate 20% improvement in anticoagulation control by
      SM. RESULTS: One hundred forty patients were randomly assigned (70 per group).
      Thirteen patients dropped out of SM early due to an inability to self-manage.
      Based on intention-to-treat analysis, there was no difference in the proportion
      of INR in range (SM 64.8% versus PM 58.7%, P=0.23) or time in target range (SM
      71.8% versus PM 63.2%, P=0.14). Patients managing their own therapy spent less
      time below the therapeutic range (15.0% versus 27.3%, P=0.04). There were three
      major complications of thrombosis or bleeding, all occurring in the PM arm. All
      patients who completed SM preferred to continue with that strategy. CONCLUSIONS:
      SM was not significantly better than PM in maintaining therapeutic
      anticoagulation. SM was feasible and appeared safe in the present study
      population.

PMID- 15457309
TI  - Measuring transient systemic conductance and capacitance responses using a
      modified Brooksby-Donald technique in anesthetized, autonomically intact rabbits.
AB  - BACKGROUND: The Brooksby-Donald approach uses two flow probes to measure the
      inflow and outflow from an organ or vascular bed; the difference in flow can be
      time-integrated to assess changes in venous capacitance. OBJECTIVES: To measure
      changes in subdiaphragmatic venous capacitance and arterial conductance in
      acutely instrumented rabbits, and to document the acute vascular responses to
      intravenous injections of pharmacological agents. METHODS: In artificially
      ventilated, fentanyl-anesthetized New Zealand female rabbits, ultrasonic flow
      probes were attached to the descending thoracic aorta and inferior vena cava to
      measure subdiaphragmatic inflow and outflow. Systemic arterial and venous
      pressures were measured. Conductance was calculated as aortic flow divided by the
      difference between systemic arterial and venous pressures. Changes in capacitance
      were assessed by integrating flow differences. Nitroglycerin (NG), isoproterenol
      hydrochloride, phenylephrine hydrochloride (PE) and vasopressin (VP) were
      administered intravenously in stepwise injections, and transient conductance and
      capacitance responses were determined. RESULTS: NG significantly increased
      conductance and capacitance, while isoproterenol hydrochloride had significant
      effects only on conductance. Both VP and PE significantly decreased conductance
      and capacitance. CONCLUSIONS: The modified Brooksby-Donald approach used in the
      present study was validated by the observed concordant increases in conductance
      and capacitance caused by NG, and decreases caused by VP and PE. This approach
      may be useful to characterize specific comparative conductance-capacitance
      properties of various vasoactive agents.

PMID- 15457310
TI  - Constrictive pericarditis: case presentation and a review of the literature.
AB  - Constrictive pericarditis (CP) is a relatively rare entity, the result of a
      thickened, scarred and often calcified pericardium, adherent to the heart and
      limiting diastolic ventricular filling. Some reported etiologies for CP include
      pericardial involvement from cardiac trauma (including surgery), mediastinal
      irradiation, tuberculosis and other infectious diseases, neoplasms and myocardial
      infarction. However, the majority of CP cases are idiopathic. This report
      presents three cases of postoperative, tuberculous and idiopathic CP,
      highlighting the clinical and pathological changes seen in CP, and a review of
      the literature.

PMID- 15457311
TI  - Kawasaki disease and scald injuries: a possible association.
AB  - The cause of Kawasaki disease (KD) is still unknown. Evidence is available to
      support both a conventional infection, as well as a superantigen-mediated
      illness. The cases of two children who were hospitalized with scald injuries are
      presented. Both patients became febrile without an infectious source and
      subsequently developed typical KD, that responded to treatment with intravenous
      immunoglobulin, without cardiac sequelae. The temporal association between the
      thermal injury and the onset of KD could be explained by the entry of an
      infectious agent(s), toxin or superantigen through the compromised skin barrier,
      leading to an inflammatory vasculitis and the clinical manifestations of KD.

PMID- 15457312
TI  - Scientific dogma-a personal experience.

PMID- 15457313
TI  - Probing history with Raman spectroscopy.
AB  - This Tutorial Review shows how Raman spectroscopic and microscopic techniques are
      utilised for non-destructive characterisation of archaeological artefacts and
      provide novel information for art historians and hints at the use of ancient
      technologies for the production and treatment of materials and skeletal remains.

PMID- 15457314
TI  - A decade of vibrational micro-spectroscopy of human cells and tissue (1994-2004).
AB  - Instrumentation used in infrared microspectroscopy (IR-MSP) permits the
      acquisition of spectra from samples as small as 100 pg (10(-10) g), and as small
      as 1 pg for Raman microspectroscopy (RA-MSP). This, in turn, allows the
      acquisition of spectral data from objects as small as fractions of human cells,
      and of small regions of microtome tissue sections. Since vibrational spectroscopy
      is exquisitely sensitive to the biochemical composition of the sample, and
      variations therein, it is possible to monitor metabolic processes in tissue and
      cells, and to construct spectral maps based on thousands of IR spectra collected
      from pixels of tissue. These images, in turn, reveal information on tissue
      structure, distribution of cellular components, metabolic activity and state of
      health of cells and tissue.

PMID- 15457315
TI  - Bis-intercalation-triggered fluorescence: specific detection of double stranded
      DNA and AT content estimation.
AB  - Detection of double stranded DNA and estimation of the AT content in DNA of
      unknown concentration could be achieved with a bis-acridinyl peptide carrying
      fluorescein, FKA.

PMID- 15457316
TI  - Immobilization of sunflower trypsin inhibitor (SFTI-1) peptide onto a gold
      surface and analysis of its interaction with trypsin.
AB  - Sunflower trypsin inhibitor (SFTI-1) derived peptide having one disulfide bond
      could be immobilized via a thiol-disulfide exchange reaction onto a gold surface
      on a quartz crystal microbalance (QCM) chip. This permitted quantitative analysis
      of the specific interaction with trypsin.

PMID- 15457317
TI  - A new class of cationic surfactants inspired by N-alkyl-N-methyl pyrrolidinium
      ionic liquids.
AB  - A series of N-alkyl-N-methylpyrrolidinium halide salts have been synthesized and
      investigated as potentially useful and tunable detergents for a variety of
      applications.

PMID- 15457318
TI  - Fast quantification of water in single living cells by near-infrared microscopy.
AB  - We have set up a near-infrared microscope using a tuneable diode laser in the
      range from 1530 to 1570 nm. This spectral range is close to the peak of the water
      overtone absorption. We used this new microscope to study liver cells,
      hepatocytes, showing that quantitative information of the intracellular water
      concentration in living cells can be extracted.

PMID- 15457319
TI  - Classification of signatures of Bovine Spongiform Encephalopathy in serum using
      infrared spectroscopy.
AB  - Signatures of Bovine Spongiform Encephalopathy (BSE) have been identified in
      serum by means of "Diagnostic Pattern Recognition (DPR)". For DPR-analysis, mid
      infrared spectroscopy of dried films of 641 serum samples was performed using
      disposable silicon sample carriers and a semi-automated DPR research system
      operating at room temperature. The combination of four mathematical
      classification approaches (principal component analysis plus linear discriminant
      analysis, robust linear discriminant analysis, artificial neural network, support
      vector machine) allowed for a reliable assignment of spectra to the class "BSE
      positive" or "BSE-negative". An independent, blinded validation study was carried
      out on a second DPR research system at the Veterinary Laboratory Agency,
      Weybridge, UK. Out of 84 serum samples originating from terminally-ill, BSE
      positive cattle, 78 were classified correctly. Similarly, 73 out of 76 BSE
      negative samples were correctly identified by DPR such that, numerically, an
      accuracy of 94.4 % can be calculated. At a confidence level of 0.95 (alpha =
      0.05) these results correspond to a sensitivity > 85% and a specificity > 90%.
      Identical class assignment by all four classifiers occurred in 75% of the cases
      while ambiguous results were obtained in only 8 of the 160 cases. With an area
      under the ROC (receiver operating charateristics) curve of 0.991, DPR may
      potentially supply a valuable surrogate marker for BSE even in cases in which a
      deliberate bias towards improved sensitivity or specificity is desired. To the
      best of our knowledge, DPR is the first and--up to now--only method which has
      demonstrated its capability of detecting BSE-related signatures in serum.

PMID- 15457320
TI  - A new FTIR-ATR cell for drug diffusion studies.
AB  - The drug diffusion of most compounds, particularly hydrophilic molecules through
      the skin is limited by the permeation of the outermost cell layers of the
      epidermis, the stratum corneum(SC). For this reason it is of interest to
      characterize drug diffusion processes through this skin layer. A new FTIR-ATR
      cell was developed for non-invasive real time measurements of drug diffusion. The
      diffusion of water through an artificial polyethyleneglycol-polydimethylsiloxane
      membrane was studied. Additionally the diffusion of urea in human SC was
      analyzed. Based on a mathematical model the diffusion coefficients were derived.
      We could reveal that this cell associates the advantages of the Franz diffusion
      cell and the FTIR-ATR spectroscopy as a new powerful method for determining drug
      diffusion through biological membranes.

PMID- 15457321
TI  - Quantitative analysis of serum and serum ultrafiltrate by means of Raman
      spectroscopy.
AB  - The fast and reliable determination of concentrations of blood, plasma or serum
      constituents is a major requirement in clinical chemistry. We explored Raman
      spectroscopy as a reagent-free tool for predicting the concentrations of
      different parameters in serum and serum ultrafiltrate. In an investigation using
      samples from 247 blood donors (which we believe to be the largest study on Raman
      spectroscopy of serum so far) the concentrations of glucose, triglycerides, urea,
      total protein, cholesterol, high density lipoprotein, low density lipoprotein and
      uric acid were determined with an accuracy within the clinically interesting
      range. After training a multivariate algorithm for data analysis, using 148
      samples, concentrations were predicted blindly for the remaining 99 serum samples
      based solely on the Raman spectra. Relative errors of prediction around 12% were
      obtained. Moreover, to the best of our knowledge, differentiation between HDL and
      LDL cholesterol as well as the quantification of uric acid was for the first time
      successfully accomplished for serum-based Raman spectroscopy. Finally, we showed
      that ultrafiltration can efficiently reduce fluorescent light background to
      improve prediction accuracy such that the relative coefficient of variation was
      reduced for glucose and urea in ultrafiltrate by more than a factor of 2 when
      compared to serum.

PMID- 15457322
TI  - Oxidative stress effects on erythrocytes determined by FT-IR spectrometry.
AB  - This study was designed to evaluate changes in erythrocyte contents during
      endurance moderate intensity exercise, a model of physiological oxidative stress.
      16 endurance-trained subjects cycled 2 h at 55% of maximal aerobic capacity and
      blood was collected every 15 min. Transmission FT-IR spectrometry was used to
      analyze separately plasma and erythrocyte content changes during oxidative
      stress. Erythrocyte FT-IR spectra were corrected for hemoconcentration (Hc)
      before spectral areas integration of main IR absorbances belonging to
      phospholipids [nu(as)(CH(3)), [nu(as)(CH(2)), and nu(P=O)], proteins [nu(C=O) and
      delta(N-H)], and lactate [nu(C-O)] were used to determine erythrocyte content
      changes. Changes in nu(as)(CH(2)) and nu(P=O) absorbances while nu(as)(CH(3))
      remained stable showed the magnitude of free radical attacks on phospholipids
      bilayer. Decrease in nu(C=O) and delta(N-H) absorbances while plasma and
      intracellular lactate, O(2) consumption, and Hc rose were linked to hemoglobin,
      and possibly spectrin, denaturation. Finally, the synergistic changes found
      between physiological, plasmatic and erythrocyte parameters showed that FT-IR
      spectrometry was a sufficiently accurate and sensitive method to determine acute
      changes in erythrocytes during moderate, physiological, oxidative stress.

PMID- 15457323
TI  - Determination of alkaloids in capsules, milk and ethanolic extracts of poppy
      (Papaver somniferum L.) by ATR-FT-IR and FT-Raman spectroscopy.
AB  - Fourier transform (FT) infrared spectroscopy using a diamond composite ATR
      crystal and NIR-FT-Raman spectroscopy techniques were applied for the
      simultaneous identification and quantification of the most important alkaloids in
      poppy capsules. Most of the characteristic Raman signals of the alkaloids can be
      identified in poppy milk isolated from unripe capsules. But also poppy extracts
      present specific bands relating clearly to the alkaloid fraction. Raman spectra
      obtained by excitation with a Nd:YAG laser at 1064 nm show no disturbing
      fluorescence effects; therefore the plant tissue can be recorded without any
      special preparation. The used diamond ATR technique allows to measure very small
      sample amounts (5-10 microL or 2-5 mg) without the necessity to perform time
      consuming pre-treatments. When applying cluster analysis a reliable
      discrimination of "low-alkaloid" and "high-alkaloid" poppy single-plants can be
      easily achieved. The examples presented in this study provide clear evidence of
      the benefits of Raman and ATR-IR spectroscopy in efficient quality control,
      forensic analysis and high-throughput evaluation of poppy breeding material.

PMID- 15457324
TI  - Analysis of human brain tissue, brain tumors and tumor cells by infrared
      spectroscopic mapping.
AB  - This study uses infrared (IR) spectroscopic, point detection, mapping procedures
      to examine tissue samples from normal brain specimens and from astrocytic
      gliomas, the most frequent human brain tumors. Model systems were derived from
      cultured glioma cell lines. IR spectra of normal tissue sections distinguished
      white matter from gray matter by increased spectral contributions from lipids and
      cholesterol. Qualitatively the same differences were found in IR spectra of low
      and high grade glioma tissue sections pointing to a significant reduction of
      brain lipids with increasing malignancy. Whereas spectral contributions of
      proteins and lipids were similar in IR spectra of glioma cells and tissues,
      nucleic acid bands were more intense for cells suggesting higher proliferative
      activities. For statistical analyses of IR spectroscopic maps from 71 samples, a
      parameter for the lipid to protein ratio was introduced involving the CH(2)
      symmetric stretch band with lipids as main contributors and the amide I band of
      proteins. As this parameter correlated with the grade of gliomas obtained from
      standard histopathological examination, it was applied to classify brain tissue
      sections based on IR spectroscopic mapping.

PMID- 15457325
TI  - Identification of secondary metabolites in medicinal and spice plants by NIR-FT
      Raman microspectroscopic mapping.
AB  - This paper demonstrates the special potential of vibrational NIR FT Raman
      microspectroscopy for the study of fennel fruits, chamomile inflorescence and
      curcuma roots to obtain detailed information about their microstructure and
      chemical composition. Microscopic Raman maps of fennel fruits demonstrate that
      anethole, which is the main essential oil component, is present in the whole
      mericarp with highest concentration at the top of the fruit. In situ measurements
      obtained of the essential oil cells are dominated by two bands observed at 1657
      cm(-1) and 1609 cm(-1) which are characteristic for anethole. Raman images of
      chamomile inflorescence show that spiroethers, identified by significant bands
      between 2150 and 2250 cm(-1), are accumulated in the middle part of the flower
      head. Due to the intense curcumin bands in the Raman spectrum of curcuma root,
      the distribution of this dyeing substance can be clearly determined; highest
      concentration of curcumin was observed on the core of the root.

PMID- 15457326
TI  - Band spreading control in electrophoresis microchips by localized zeta-potential
      variation using field-effect.
AB  - The paper proposes a new technique, which varies the zeta potential along the
      channel walls in the vicinity of the microchannel corners in such as a way as to
      minimize the effects of turn-induced dispersion within U-shaped separation
      channels. The effects of the separation channel geometry, the fluid velocity
      profile, and boundary control of the zeta potential on the band distribution in
      the detection area are all discussed within this paper. The results for the
      folded square U-shaped separation channel indicate that boundary control of the
      zeta potential by field-effect significantly reduces the band dispersion induced
      by the 90[degree] turns. Finally, the results confirm that application of the
      proposed localized zeta potential variation method results in a correction of the
      band tilting phenomenon and a reduction in the racetrack effect.

PMID- 15457327
TI  - Separation of lipids from blood utilizing ultrasonic standing waves in
      microfluidic channels.
AB  - A method to continuously separate different particle types in a suspension is
      reported. Acoustic forces in a standing wave field were utilized to discriminate
      lipid particles from erythrocytes in whole blood. The presented technology
      proposes a new method of cleaning, i.e. removing lipid emboli from, shed blood
      recovered during cardiac surgery. Blood contaminated with lipid particles enter a
      laminar flow micro channel. Erythrocytes and lipid particles suspended in blood
      plasma are exposed to a half wavelength standing wave field orthogonal to the
      direction of flow as they pass through the channel. Because of differences in
      compressibility and density the two particle types move in different directions,
      the erythrocytes towards the centre of the channel and the lipid particles
      towards the side walls. The end of the channel is split into three outlet
      channels conducting the erythrocytes to the centre outlet and the lipid particles
      to the side outlets due to the laminar flow profile. The separation channel was
      evaluated in vitro using polyamide spheres suspended in water, showing separation
      efficiencies approaching 100%. The system was also evaluated on whole blood using
      tritium labelled lipid particles added to bovine blood. More than 80% of the
      lipid particles could be removed while approximately 70% of the erythrocytes were
      collected in one third of the original fluid volume. The study showed that the
      further reduced micro channel dimensions provided improved performance with
      respect to; (i) separation efficiency, (ii) actuation voltage, and (iii)
      volumetric throughput as compared to earlier work.

PMID- 15457328
TI  - An integrated AC electrokinetic pump in a microfluidic loop for fast and tunable
      flow control.
AB  - We have built a dedicated lab on a chip to study the performance of an integrated
      electrokinetic micropump, driven by a low voltage AC signal. This micropump
      consists of an array of interdigitated electrodes and is here integrated in a
      microfluidic loop. We demonstrate that this device can pump continuously and
      reproducibly electrolyte solutions of low to moderate ionic strength. The pumping
      speed reaches up to 500 [micro sign]m s(-1) in 20 [micro sign]m deep and 100
      [micro sign]m wide channels with a driving signal in the 1-10 kHz range and an
      amplitude of only a few volts. In addition, we have observed an interesting
      reversal of the pumping direction at higher frequencies (50-100 kHz). Our device
      permits a systematic and automated exploration of the influence of the ionic
      strength thanks to an integrated micromixer.

PMID- 15457329
TI  - Correlation of optical properties with structure of immobilised nanoparticles--a
      method for probing the mechanism of SERRS.
AB  - A combined surface enhanced resonance Raman scattering (SERRS) and transmission
      electron microscopy (TEM) method has been developed allowing the same immobilised
      nanoparticles to be reliably located and studied by both techniques. The method
      allows large numbers of particles to be analysed by each technique relatively
      simply and the distribution of Raman enhancement between particles and clusters,
      as well as the relationship between particle microstructure and Raman
      enhancement, to be investigated. In addition, the effect of chemical and laser
      damage on the dye on the surface of the particles and the effect on the particles
      can be systematically investigated. These effects can cause time dependence
      fluctuations in Raman signals which could be confused with "blinking" from single
      molecules. Conditions were identified to enable Raman scattering to be detected
      without photodegradation to either the analyte molecules or the particles.
      Measurement outside this range gave rise to alterations in the spectra and to
      loss of signal. The extent of the damage to the analyte/particle if these
      conditions are not adhered to gives rise for concern about interpretation of
      changes in spectra observed unless an attempt is made to assess the limits of the
      conditions which can be applied before photodegradation or sample drying occurs.
      The method developed will enable reliable and systematic studies of the
      enhancement obtained from immobilised single particles by enabling the full power
      of high resolution TEM to be utilised to aid the development of a reliable SERRS
      theory.

PMID- 15457330
TI  - Raman spectroscopic analyses of preserved historical specimens of human hair
      attributed to Robert Stephenson and Sir Isaac Newton.
AB  - The Raman spectra of two historical specimens of human hair attributed to the
      engineer Robert Stephenson and scientist Sir Isaac Newton, preserved in private
      collections are reported. Comparisons are made with the Raman spectra of modern
      hair specimens and with hair from archaeological excavations. The hair spectra
      collected with a laser excitation of 785 nm are of a better quality than those
      collected using 1064 nm. The historical hair specimens are remarkably well
      defined spectroscopically in terms of the amide I vibrational mode and the [small
      nu](SS), ascribed to a predominantly gauche-gauche-gauche CSSC conformation. The
      contrast with degraded hair specimens recovered from archaeological excavations
      is striking. The presence of a weak feature near 2590 cm(-1) in the hair samples
      attributed to a [small nu](SH) vibration could be indicative of a reduction
      process operative on the CSSC cystine keratotic linkages and a possible origin of
      this is bacterial biodegradation identified histologically. This study
      demonstrates the molecular information available from non-destructive Raman
      spectroscopic analysis from single hair shafts or small bundles of fibres which
      complements information available from histological and destructive analytical
      techniques for rare biological specimens subjected to conservation or curation
      procedures in museums or private collections.

PMID- 15457331
TI  - Developing rapid detection of mycobacteria using microwaves.
AB  - In this paper, we describe the development of a culture-based biochip device for
      rapid detection of mycobacteria in environmental samples. Individual biochips
      rely upon the unique paraffinophilic nature of mycobacteria to rapidly and
      selectively adhere to the surface of the device. We used prototype biochips to
      experimentally demonstrate the concept of rapid and selective detection of
      mycobacteria by testing pure cultures and using epifluorescence microscopy to
      visualize microorganisms on the surface. As an alternative, rapid approach for
      identifying the biomass on the biochip surface, we used microwaves in the 10 to
      26 GHz frequency range. The results of this study indicate that different
      microorganisms are responsible for specific shifts in resonance frequencies of a
      microwave cavity. By combing the semi-selective paraffin surface of the biochip
      with the microorganism-specific response to the microwaves, we have developed an
      improved analytical system with the potential to rapidly identify and enumerate
      mycobacteria in environmental samples in as little as 2 h.

PMID- 15457332
TI  - Sub-picomole colorimetric single nucleotide polymorphism discrimination using
      oligonucleotide-nanoparticle conjugates.
AB  - Oligonucleotide-gold nanoparticle conjugates are employed to demonstrate
      selective colorimetric discrimination of a cystic fibrosis-related genetic
      mutation in a model oligonucleotide system. Specifically, three strand
      oligonucleotide complexes are employed, wherein two probe oligonucleotide-gold
      nanoparticle conjugates are linked together by a third target oligonucleotide
      strand bearing the chosen CF-related mutation. By monitoring the solution optical
      absorption behaviour of the complexes as a function of temperature, melting
      profiles may be accurately acquired and reproducibly compared. Following this
      method, fully complementary sequences are successfully distinguished from
      mismatched sequences, with single base mismatch resolution, for the V232D
      mutation. To extend the detection sensitivity of this oligonucleotide
      nanoparticle conjugate assay, a novel and compact LED-based optical monitoring
      system capable of sub-picomole level colorimetric SNP discrimination is also
      demonstrated.

PMID- 15457333
TI  - SERRS dyes. Part 3. Synthesis of reactive benzotriazole azo dyes for surface
      enhanced resonance Raman scattering.
AB  - A series of eleven specially designed benzotriazole monoazo dyes for use in
      surface enhanced resonance Raman scattering studies are reported. Unlike previous
      benzotriazole dyes produced for SERRS, these dyes have been synthesised to be
      trifunctional in nature. The presence of the benzotriazole moiety provides
      surface complexing properties, the azo linkage provides the colour and hence
      extra sensitivity and the nucleophilic amine group enables further
      functionalisation.

PMID- 15457334
TI  - Buffer composition changes in background electrolyte during electrophoretic run
      in capillary zone electrophoresis.
AB  - The electrophoretic behaviors of different analytes in capillary zone
      electrophoresis were studied by the Whole Column Imaging Detection (WCID). For
      capillary zone electrophoresis (CZE) in conventional buffer systems, non-constant
      sample plug movement characterized by progressive decrease of peak migration
      velocity was observed. The appropriate velocity decrease was correlated with a
      degree of ionization of the analyzed ion, thus the effect observed could be
      explained by fast buffer composition change resulting in the development of a non
      linear pH gradient. To visualize the appropriate pH gradient, the concentration
      profile of initially uniformly distributed amphoteric substances was also
      monitored. The evolution of the concentration profile exhibited very complex
      dynamics. In addition, it was found that the nature of the electrode solutions
      strongly affect changes in the background electrolyte. In the case of traditional
      background electrolytes with an acid-base pair for electrode solutions a non
      uniform ampholyte concentration developed quickly, leading finally to a quasi
      stationary profile similar to those typical of IEF. Possible approaches to
      suppress a negative impact of the background electrolyte composition changes
      during electrophoretic run on CE-separation are presented herein. In particular
      it was observed that zwitterionic buffers are able to withstand prolonged
      electrolysis much better compared to traditional buffers.

PMID- 15457335
TI  - Vrms/T quantitation in patients with lumbar spinal stenosis.
AB  - Thirty consecutive patients with clinical and radiographic findings consistent
      with lumbosacral root injury were evaluated. Electrodiagnostic examinations
      included determination of root mean square (Vrms)/turns (T) values. Vrms/T values
      > or =1 are consistent with chronic neurogenic injury and have been correlated
      with increase in fiber density. Radiographic studies were independently
      classified as having severe (group I; n= 8), mild (group II; n=11), or no lumbar
      spinal stenosis (group III; n=11). Abnormal Vrms/T values were present in all 8
      patients in group I in comparison to 0/11 in group II and 2/11 in group III
      (p<0.0001 and 0.0007 respectively in comparison to group I). In 5/8 patients in
      group I, Vrms/T values provided unique information. Large amplitude motor units
      were also present more frequently in group I in comparison to the other groups
      (p<0.02). This study indicates Vrms/T values can be helpful in the
      electrodiagnostic evaluation of patients with lumbosacral radiculopathies,
      particularly where chronic multilevel radicular injury might be expected such as
      in lumbar spinal stenosis.

PMID- 15457336
TI  - A simple procedure using auditory stimuli to improve movement in Parkinson's
      disease: a pilot study.
AB  - It has been suggested that sequential movements in Parkinsonian patients might be
      improved by the effects of external rhythmic cues, either visual or acoustic,
      acting as a sort of timekeeper. In line with that idea, we have developed a
      portable system which allows the patient suffering from bradykinesia and rigidity
      to initiate appropriate auditory stimulation when he/she is not able to move.
      Here we present data from six Parkinson's Disease (PD) patients studied with
      surface electromyography, while walking along an 8.5m walkway. All showed
      remarkable improvement in the EMG parameters studied while using the device. The
      results are consistent with prior reports on rhythmic auditory facilitation in
      Parkinson's disease gait,and suggest that this represents a novel and inexpensive
      tool to help people afflicted by PD in daily motor performance.

PMID- 15457337
TI  - Monoallelic expression of mouse Cd4 gene.
AB  - A 7-bp deletion in the Cd4 gene, present in the strain MOLF/Ei of Mus musculus
      molossinus and absent in laboratory mouse strains ( Mus musculus musculus),
      provided the means to distinguish the parental origin of the Cd4 alleles
      expressed in single cells of F1 (AKR x MOLF/Ei) and F1 (Balb/C x MOLF/Ei)
      hybrids. Single-cell RT-PCR showed that the individual CD4+ lymphocyte expresses
      either the maternal or the paternal Cd4 allele, never both. In situ hybridization
      proved that Cd4 alleles replicate asynchronously, as expected in the case of
      genes expressed monoallelically.

PMID- 15457338
TI  - A gene-driven ENU-based approach to generating an allelic series in any gene.
AB  - N-ethyl-N-nitrosourea (ENU) introduces mutations throughout the mouse genome at
      relatively high efficiency. Successful high-throughput phenotype screens have
      been reported and alternative screens using sequence-based approaches have been
      proposed. For the purpose of generating an allelic series in selected genes by a
      sequence-based approach, we have constructed an archive of over 4000 DNA samples
      from individual F1 ENU-mutagenized mice paralleled by frozen sperm samples.
      Together with our previously reported archive, the total size now exceeds 6000
      individuals. A gene-based screen of 27.4 Mbp of DNA, carried out using denaturing
      high-performance liquid chromatography (DHPLC), found a mutation rate of 1 in
      1.01 Mbp of which 1 in 1.82 Mbp were potentially functional. Screening of whole
      or selected regions of genes on subsets of the archive has allowed us to identify
      15 new alleles from 9 genes out of 15 tested. This is a powerful adjunct to
      conventional mutagenesis strategies and has the advantage of generating a variety
      of alleles with potentially different phenotypic outcomes that facilitate the
      investigation of gene function. It is now available to academic collaborators as
      a community resource.

PMID- 15457339
TI  - QTLs for pre- and postweaning body weight and body composition in selected mice.
AB  - In an intercross between the high-body-weight-selected mouse line NMRI8 and the
      inbred line DBA/2, we analyzed genetic effects on growth during the suckling
      period and after weaning during the juvenile phase of development. QTL mapping
      results indicated that a switch of gene activation might occur at the age of
      three weeks when animals are weaned. We found QTLs for body weight with major
      effects at the age of two and three weeks when animals are fed by their mothers,
      and QTLs with highest effects after weaning when animals have to live on their
      own under ad libitum access to food. Specific epistatic effects on body weight at
      two and three weeks and epistatic interaction influencing growth after weaning
      support this finding. QTL effects explained the greatest variance during puberty
      when animals grow fastest and become fertile. In the present study, all except
      one QTL effect for early body weight had dominance variance components. These
      might result from direct single-locus-dominant allelic expression, but also from
      the identified epistatic interaction between different QTLs that we have found
      for body weight at all ages. Beside body weight, body composition traits (muscle
      weight, reproductive fat weight, weight of inner organs) were analyzed. Sex
      dimorphic QTLs were found for body weight and fat deposition. The identified
      early-growth QTLs could be the target of epigenetic modifications which might
      influence body weight at later ages.

PMID- 15457340
TI  - Mapping of a quantitative trait locus for morphine withdrawal severity.
AB  - Chronic morphine exposure results in physical dependence, manifested by physical
      symptoms during naloxone-precipitated withdrawal. Jumping frequency is widely
      considered the most sensitive and reliable index of withdrawal intensity in mice.
      Inbred mouse strains surveyed for naloxone-precipitated withdrawal display large
      and significant strain differences in jumping frequency, including an
      approximately tenfold difference between C57BL/6 and 129P3 mice. In the present
      study, (B6 x 129)F2 hybrid mice were given daily morphine injections for four
      days using an escalating dosing schedule, and naloxone-precipitated withdrawal on
      day 5 was measured. A full-genome scan for linkage to phenotypic data was
      performed using polymorphic microsatellite markers. Significant linkage was
      observed between withdrawal jumping frequencies and a 28 cM-wide region of
      Chromosome 1 (32-60 cM; peak at 51 cM), accounting for 20% of the overall
      phenotypic variance. Two other suggestive QTLs were found, on Chromosomes 5 and
      10, and an additive model fitting all three loci accounted for 43% of the total
      variance. F2 mice were also assessed for changes in morphine analgesic potency
      using the tail-withdrawal test in dose-response studies on days 1 and 4. No
      linkage was observed between Chromosomes 1, 5, and 10 and morphine analgesic
      tolerance, suggestive of genetic dissociation of naloxone-precipitated withdrawal
      from morphine and chronic morphine intake per se. The significant quantitative
      trait locus for naloxone-precipitated withdrawal severity in morphine-dependent
      mice, which we name Depmq1, may prove to be of considerable heuristic value once
      the underlying gene or genes are identified.

PMID- 15457341
TI  - Distinct PAR/IQGAP expression patterns during murine development: implications
      for thrombin-associated cytoskeletal reorganization.
AB  - Thrombin has a critical role in many adult and embryologic cellular processes,
      exerting its effects through two high-affinity thrombin receptor systems:
      protease-activated receptor 1 (PAR1) and the PAR3/PAR4 system. Both hPAR1 and
      hPAR3 are coclustered in the human genome, with hPAR3 encompassed within hIQGAP2,
      a putative GTPase activating protein with actin polymerizing functions linked to
      cytoskeletal reorganization. Since hPARs colocalize with hIQGAP2 in the human
      genome and function coordinately with this protein in platelet thrombin signaling
      pathways, we have further characterized these genes in developing embryonic and
      adult tissues. We confirmed the presence of a mIQGAP2/ mPAR gene cluster on
      murine Chromosome 13 and showed it to be organized similarly to that in humans,
      except that murine PAR3 is translated off the forward (sense) strand. Northern
      analysis demonstrated limited mPAR3 expression in adult tissues, although its
      expression during embryogenesis was evident at E15 in cartilage, brain, and
      keratinocytes. mIQGAPs 1 and 2 had congruent expression patterns in 11 of 15
      adult tissues studied. In contrast, whole embryos demonstrated predominant
      mIQGAP1 expression starting at E7 and evident to E17. In situ hybridization of
      whole embryos (E9-E16) demonstrated distinct patterns of tissue-dependent
      mIQGAP1/ mIQGAP2 expression. Concordant expression (absence or presence) of mPAR1
      with either mIQGAP1 or mIQGAP2 was seen in the majority (12 of 15) of adult
      tissues studied. Similarly, there was no evidence for mPAR3 expression during
      embryogenesis in the absence of either mIQGAP1 or mIQGAP2. These data provide a
      panoramic survey of PAR/ IQGAP expression as an initial approach to dissect
      thrombin signaling pathways linked to cytoskeletal reorganization.

PMID- 15457342
TI  - Quantitative trait loci in Chromosomes 3, 8, and 9 regulate antibody production
      against Salmonella flagellar antigens in the mouse.
AB  - Two mouse lines were produced by bidirectional selection according to the high
      (HIII) or low (LIII) antibody responsiveness against Salmonella flagellar
      antigens (Selection III). In the present work we conducted a genomewide scan to
      map the quantitative trait loci (QTL) involved in the antibody response
      regulation in these selected mice. HIII and LIII genomes were screened with
      microsatellite markers and those found polymorphic between the lines (146) were
      used for linkage analysis in F2 (HIII x LIII) intercross. Simple interval mapping
      analysis was performed using Mapmanager QTX software. Three highly significant
      QTL linked to antibody production against Salmonella flagellar antigens have been
      demonstrated in Chromosomes 3, 8, and 9. HIII and LIII lines differ in the
      resistance to several diseases, therefore, the relevance of these QTL with the
      genetic factors involved in infections, autoimmunity, and neoplastic disease
      progression is discussed.

PMID- 15457343
TI  - Genetic structure of the LXS panel of recombinant inbred mouse strains: a
      powerful resource for complex trait analysis.
AB  - The set of LXS recombinant inbred (RI) strains is a new and exceptionally large
      mapping panel that is suitable for the analysis of complex traits with
      comparatively high power. This panel consists of 77 strains-more than twice the
      size of other RI sets--and will typically provide sufficient statistical power
      (beta = 0.8) to map quantitative trait loci (QTLs) that account for approximately
      25% of genetic variance with a genomewide p < 0.05. To characterize the genetic
      architecture of this new set of RI strains, we genotyped 330 MIT microsatellite
      markers distributed on all autosomes and the X Chromosome and assembled error
      checked meiotic recombination maps that have an average F2-adjusted marker
      spacing of approximately 4 cM. The LXS panel has a genetic structure consistent
      with random segregation and subsequent fixation of alleles, the expected 3-4 x
      map expansion, a low level of nonsyntenic association among loci, and complete
      independence among all 77 strains. Although the parental inbred strains-Inbred
      Long-Sleep (ILS) and Inbred Short-Sleep (ISS)--were derived originally by
      selection from an 8-way heterogeneous stock selected for differential sensitivity
      to sedative effects of ethanol, the LXS panel is also segregating for many other
      traits. Thus, the LXS panel provides a powerful new resource for mapping complex
      traits across many systems and disciplines and should prove to be of great
      utility in modeling the genetics of complex diseases in human populations.

PMID- 15457344
TI  - Sex- and lineage-specific inheritance of depression-like behavior in the rat.
AB  - The Wistar-Kyoto (WKY) rat exhibits physiological and behavioral similarities to
      endophenotypes of human depression. In the forced swim test (FST), a well
      characterized antidepressant-reversible test for behavioral despair in rodents,
      WKYs express characteristics of behavioral despair; increased immobility, and
      decreased climbing. To map genetic loci linked to behavior in the FST, we
      conducted a quantitative trait loci (QTL) analysis of the segregating F2
      generation of a WKY x Fisher 344 (F344) reciprocal intercross. Using linear-model
      based genome scans to include covariate (sex or lineage)-by-QTL interaction
      effects, four significant QTL influencing climbing behavior were identified. In
      addition, we identified three, seven, and two suggestive QTL for climbing,
      immobility, and swimming, respectively. One of these loci was pleiotropic,
      affecting both immobility and climbing. As found in human linkage studies,
      several of these QTL showed sex- and/or lineage-dependent effects. A simultaneous
      search strategy identified three epistatic locus pairs for climbing. Multiple
      regression analysis was employed to characterize the joint contributions of these
      QTL and to clarify the sex- and lineage-dependent effects. As expected for
      complex traits, FST behavior is influenced by multiple QTL of small effect, each
      contributing 5%-10%, accounting for a total 10%-30% of the phenotypic variance. A
      number of loci mapped in this study share overlapping candidate regions with
      previously identified emotionality QTL in mice as well as with susceptibility
      loci recognized by linkage or genome scan analyses for major depression or
      bipolar disorder in humans. The presence of these loci across species suggests
      that these QTL may represent universal genetic factors contributing to mood
      disorders.

PMID- 15457345
TI  - Imprinting of Nesp55 gene in cattle.
AB  - Studies in mouse and human have established that the exon encoding the
      neuroendocrine secretory protein Nesp55 is transcribed exclusively from the
      maternal allele. To study the imprinting status of Nesp55 in cattle, we examined
      transcripts of this exon in a wide range of tissues from four fetuses and the dam
      of one of the fetuses (not all tissues were examined in all subjects). A
      polymorphic site was used to determine transcript status as monoallelic or
      biallelic. The expression analysis was by direct sequencing of RT-PCR products
      amplified from the tissues. Nesp55 transcripts were detected in many tissues, in
      contrast to previous studies in which Nesp55 was detected by immunoassays in
      endocrine and nervous tissues only. In all five individuals, Nesp55 showed
      monoallelic expression. In one of the fetuses, parental origin of the expressed
      allele could not be determined; in the others monoallelic expression was clearly
      maternal. Thus, bovine Nesp55 is maternally expressed like its counterparts in
      mouse and human.

PMID- 15457346
TI  - hRDH-E2 gene polymorphisms, variable transcriptional start sites, and psoriasis.
AB  - hRDH-E2 is a member of the short-chain alcohol dehydrogenase/reductase (SDR)
      family that converts retinol to retinaldehyde as the first and rate-limiting step
      in the retinoic acid synthetic pathway. This pathway is critical for the
      maintenance of epidermal homeostasis in vivo. Previously, we reported that the
      mRNA levels of hRDH-E2 in psoriatic skin were elevated significantly compared
      with that in healthy individual skin and psoriatic unaffected skin. The gene
      encoding hRDH-E2 is located on Chromosome 8 close to a candidate region for
      psoriasis and therefore is a functional and positional candidate for this
      disorder. In the present study, the transcription start sites for hRDH-E2 gene
      transcription in the lung were found to be more upstream of those that were
      identified previously in keratinocytes. Consequently, differences in the
      nucleotide sequence were determined for all of the coding exons, untranslated
      regions, and at least 2850 bp of 5'-noncoding sequence of hRDH-E2 by direct
      sequencing of polymerase chain reaction (PCR)-amplified DNA samples obtained from
      8 psoriatic patients and 8 healthy controls. One polymorphic microsatellite
      marker at the noncoding 3' end of the gene and six single nucleotide
      polymorphisms (SNPs) (three in the 5' flanking sequence, two in the coding
      sequence, and one in the intronic sequence) were identified. One of the SNPs was
      nonsynonymous in the second exon with an allelic variation between the amino acid
      sequences Arg and Trp. The microsatellite marker and the six SNPs were all
      genotyped in 100 Japanese psoriatic patients and 120 controls. However, there
      were no statistically significant differences in the genotype or allele frequency
      distributions between the cases and controls. On this basis, we conclude that the
      polymorphisms that we detected for the hRDH-E2 gene do not contribute to the
      etiology of psoriasis but may be important in diseases of other tissues.

PMID- 15457348
TI  - Treatment of hydatid cyst of the liver: where is the evidence?
AB  - Treatment of hydatid cyst of the liver ranges from surgical intervention
      (conventional or laparoscopic approach) to percutaneous drainage and to medical
      therapy. The aim of this systematic review was to provide "evidence-based"
      answers to the following questions: Should chemotherapy be used alone or in
      association with surgery? What is the best surgical technique? When is the
      percutaneous aspiration injection and reaspiration technique (PAIR) indicated? An
      extensive electronic search of the relevant literature without limiting it to the
      English language was carried out using MEDLINE and the Cochrane Library. Key
      words used for the final search were "hydatid cyst," "liver," "treatment," "meta
      analysis," "randomized controlled trial," "prospective study," "retrospective
      study." All relevant studies reporting the assessment of one modality of
      treatment or a comparison of two or several therapeutic methods to treat hydatid
      cyst of the liver and published in a peer-reviewed journal were considered for
      analysis. This systematic review allowed us to conclude that chemotherapy is not
      the ideal treatment for uncomplicated hydatid cysts of the liver when used alone
      (level II evidence, grade B recommendation). The level of evidence was too low to
      help decide between radical or conservative treatment (level IV evidence, grade C
      recommendation). Omentoplasty associated with radical or conservative treatment
      is efficient in preventing deep abscesses (level II evidence, grade A
      recommendation). The laparoscopic approach is safe (level IV evidence, grade C
      recommendation). Drug treatment associated with surgery (level II evidence, grade
      C recommendation) requires further studies. Percutaneous drainage associated with
      albendazole therapy is safe and efficient in selected patients (level II
      evidence, grade B recommendation). The level of evidence is low concerning
      treatment of complicated cysts.

PMID- 15457349
TI  - Laparoscopic cholecystectomy as a day surgery procedure: implementation and audit
      of 136 consecutive cases in a university hospital.
AB  - Laparoscopic cholecystectomy (LC) has been routinely performed since 1989 at our
      institution, and patients were traditionally admitted for 2 days. In 1996 we
      implemented a protocol for LC as a day surgery procedure at our center. Although
      initially reported by others, it has not yet been introduced as routine in
      Switzerland. The objective of this prospective study was to determine
      acceptability and safety of LC as an outpatient procedure in a university
      hospital. Data were collected prospectively for 136 LCs between January 1996 and
      December 2001. Patients were selected for the study if they wanted to go home
      within less than 24 hours, had no previous jaundice, and had no anesthetic
      contraindication. Systematic preoperative liver function tests and hepatic
      ultrasonography were performed. All patients were admitted on the day of
      operation. LC was performed using a three-trocar technique. Systematic
      cholangiography was performed, and all the procedures were completed
      laparoscopically. There were no common bile duct explorations. Postoperative
      complications were the following: nausea in seven patients, a minor umbilical
      hematoma in two. According to patient preference, 101 (74%) were discharged after
      an overnight stay (less than 24 hours) and 32 (24%) on the same day. The
      unplanned admission rate was 2%, and none of the patients was subsequently
      readmitted. The reasons for unplanned admissions were two patients with
      persistent nausea and one patient for whom an overnight stay was scheduled who
      presented with a ruptured subcapsular hematoma of the liver. Altogether, 97% of
      the patients were satisfied with the care they received. Operative costs were not
      significantly different when comparing inpatient and outpatient LC. The main
      postoperative savings were in the postoperative costs. Our results confirm that
      LC as a day surgery procedure is safe, effective, and acceptable to patients and
      their relatives. These results were achieved by using selection criteria that
      considered not only the surgical pathology but also the individual and by using
      appropriate techniques and planned postoperative analgesia.

PMID- 15457350
TI  - Local anesthesia use for laparoscopic cholecystectomy.
AB  - This study aimed to investigate the effects and timing of local anesthesia during
      laparoscopic surgery in terms of postoperative pain, nausea, and the need for
      opioids and antiemetics. This prospective study was carried out on 142 patients
      who underwent laparoscopic cholecystectomy. Peroperative local anesthesia was not
      administered to 53 patients (group A). The skin, subcutis, fascia, and parietal
      peritoneum were infiltrated with 0.5% bupivacaine HCl at trocar sites before
      trocar insertion in 46 patients (group B). Local anesthesia was given to 43
      patients in equal doses at the same sites and the same manner at the end of
      surgery (group C). The higher requirement for analgesics in group A patients was
      statistically significant when compared with that in group B and C patients. The
      mean doses of analgesics postoperatively were significantly higher in group B
      than in group C. The time delay to the first antiemetics was significantly
      shorter in group A than in group C. Applying local anesthesia to the skin,
      subcutis, fascia, and parietal peritoneum through trocar sites reduces the
      postoperative analgesic requirement and pain intensity. This approach is more
      effective when applied at the end of an operation than at the start.

PMID- 15457351
TI  - Outcome of laparoscopic cholecystectomy in patients 80 years and older.
AB  - Advanced age is associated with an increase in postoperative complications. This
      study assesses the indications and outcome for laparoscopic cholecystectomy (LC)
      in patients aged 80 years or older. Consecutive, unselected patients aged 80
      years or over undergoing LC between 1991 and 2000 were included. A retrospective
      case review enabled analysis of clinical and operative factors together with in
      hospital morbidity, 30-day mortality, and duration of hospital stay. A series of
      117 patients, 79 women and 38 men with a median age of 83 years (range 80-93
      years), underwent LC. Indications for LC were chronic cholecystitis in 62 (53%)
      patients, acute cholecystitis in 28 (24%), gallstone pancreatitis in 12 (10%),
      and other conditions in 15 (13%). Six (5%) patients required conversion to an
      open procedure. Overall, 26 (22%) patients developed a postoperative
      complication. There were no bile leaks or bile duct injuries. One patient, with
      gangrenous cholecystitis, died after LC. The median postoperative hospital stay
      was 3 days (range 1-31 days). LC can be performed safely with low morbidity in
      patients over age 80 years.

PMID- 15457352
TI  - Pleurodesis in patients with malignant pleural effusions: talc slurry or
      bleomycin? Results of a prospective randomized trial.
AB  - The purpose of this study was to evaluate the efficacy, safety, and cost of
      bedside pleurodesis for malignant pleural effusions using talc slurry (TS) or
      bleomycin (BL) in a prospective randomized trial, and to determine
      prognosticators for procedure failure. From June 1997 to June 1999 a series of 71
      patients entered this trial. They underwent 37 procedures with TS (4 g) and 34
      with BL (60 units) via tube thoracostomy. Success was defined as no recurrence of
      pleural effusion or asymptomatic recurrence of a small amount of effusion.
      Pleural effusion-free survival curves were used to analyze the success rates and
      the prognosticators of failure. Follow-up ranged from 3 days to 26 months (median
      2.5 months). No difference in success rates was detected between TS or BL (log
      rank test: p = 0.724). There were no major complications related to the
      procedure. The independent prognosticators of failed pleurodesis were the use of
      steroids ( p = 0.004) and the volume of pleural fluid drained during the first
      thoracentesis when it was more than 900 ml ( p = 0.029). The average cost of
      intervention per patient was significantly lower for TS ( p < 0.001). There was
      no significant difference between the success rates for TS and BL as agents of
      bedside pleurodesis for malignant pleural effusions. Because of its significantly
      lower cost, TS should be considered the agent of choice. The use of steroids and
      the volume drained during the first thoracentesis (if more than 900 ml) were
      independent prognosticators of pleurodesis failure. The role of this latter
      finding as a marker of pleurodesis failure awaits more data.

PMID- 15457354
TI  - Recurrent laryngeal nerve identification and assessment during thyroid surgery:
      laryngeal palpation.
AB  - Electrical identification and monitoring of the recurrent laryngeal nerve (RLN)
      has been proposed as an adjunct to standard visual identification of the nerve
      during thyroid and parathyroid surgery. This study was undertaken to assess
      laryngeal palpation as an intraoperative technique for identifying and assessing
      the RLN during surgery and to investigate the relation between laryngeal
      palpation and associated laryngeal electromyographic (EMG) activity. The
      postcricoid region of the larynx during surgery was palpated through the
      posterior hypopharyngeal wall to sense posterior cricoarytenoid muscle
      contraction in response to ipsilateral RLN stimulation (i.e., the "laryngeal
      twitch response.") Laryngeal palpation was performed in a series of 449
      consecutive thyroid and parathyroid surgeries with 586 RLNs at risk. All patients
      underwent preoperative and postoperative laryngoscopy to assess vocal cord
      mobility. In a subset of patients, laryngeal palpation and simultaneous laryngeal
      EMG recordings were compared during intraoperative RLN stimulation. In this
      series, there was no permanent RLN paralysis. There was one case of temporary RLN
      paralysis secondary to neural stretch that resolved 6 weeks postoperatively
      (temporary paralysis rate: 0.2% of patients, 0.2% of nerves at risk).
      Intraoperative laryngeal palpation of the laryngeal twitch response reliably
      correlated with normal postoperative vocal cord function. Loss of the laryngeal
      twitch response occurred in the single case of temporary paralysis in the setting
      of an anatomically intact nerve. Laryngeal palpation correlated well with
      simultaneous laryngeal EMG activity. There were no palpation-induced laryngeal
      injuries or laryngeal edema. There were also no RLN injuries due to repetitive
      neural stimulation. Intraoperative laryngeal palpation during RLN stimulation is
      a safe, reliable method for neural monitoring that can assist in RLN
      identification and assessment during thyroid and parathyroid surgery. Most
      importantly, it provides important prognostic information regarding ipsilateral
      vocal cord function at the completion of the initial side of the thyroid or
      parathyroid surgery. Intraoperative laryngeal palpation allows the surgeon to
      stage contralateral surgery if RLN damage is diagnosed, thereby avoiding the
      potential for bilateral vocal cord paralysis. We believe that laryngeal palpation
      is useful as an adjunct to formal EMG monitoring during thyroid and parathyroid
      surgery.

PMID- 15457355
TI  - Factors predicting malignancy of Hurthle cell tumors of the thyroid: influence on
      surgical treatment.
AB  - Controversy still exists about the ability to differentiate between malignant and
      benign Hurthle cell tumors (HCTs) before and during surgery. Diagnostic
      difficulties make surgical decisions debatable. The aim of this study was to
      evaluate factors predicting the malignancy of HCT and to plan its appropriate
      management. From January 1998 to May 2003 a series of 41 patients underwent
      thyroidectomy in our surgical department because of HCT. A cross-sectional study
      of 23 patients with carcinoma and 18 patients with adenoma was carried out:
      demographic data, tumor characteristics, diagnostic results of fine-needle
      aspiration cytology (FNAC), frozen section (FS), MIBI scan scintigraphy, surgical
      indications, and treatment were evaluated. The mean tumor size was significantly
      greater for carcinomas than adenomas (3.1 vs. 1.9 cm; p = 0.006). Threshold sizes
      of more than 3.0 cm and 4.0 cm, respectively, were significant for predicting
      malignancy ( p = 0.025 and p = 0.012). Conversely, 47.8% of carcinomas had a
      diameter smaller than 3.0 cm. FNAC and FS sensitivities for carcinoma detection
      were 23.8% and 33.3%, respectively. The positive uptake on MIBI scan imaging was
      likely to be similarly malignant or benign. Because of the lack of accuracy of
      all diagnostic studies for predicting malignancy, all oxyphilic cell nodules
      should be referred to surgery. Different tumor sizes cannot be the only factor on
      which to base a surgical decision. Therefore, because of diagnostic
      uncertainties, we believe that an experienced surgeon can safely perform total
      thyroidectomy in all patients with an HCT.

PMID- 15457356
TI  - Novel operative technique for vagal nerve- and pyloric sphincter-preserving
      distal gastrectomy reconstructed by interposition of a 5 cm jejunal J pouch with
      a 3 cm jejunal conduit for early gastric cancer and postoperative quality of life
      5 years after operation.
AB  - The importance of the vagal nerve and pyloric sphincter, the need for pouch
      reconstruction, and the ideal pouch volume are all matters of controversy. A
      novel operative technique for vagal nerve- and pyloric sphincter-preserving
      distal gastrectomy reconstructed by interposition of a 5 cm jejunal J pouch with
      a 3 cm jejunal conduit was developed as a function-preserving surgical technique
      to prevent postgastrectomy disorders. The application criteria and technique are
      outlined in this article. Postoperative quality of life was also investigated
      clinically. Twenty subjects who underwent this surgical operation (group A: 16
      men and 4 women aged 41 to 70 years, mean age 59.5 years) were interviewed to
      inquire about postoperative gastrointestinal symptoms. These patients were
      compared with 44 others who underwent conventional distal gastrectomy with D2
      lymphadenectomy (group B: 30 men and 14 women aged 43 to 73 years, mean age 62.6
      years). Included were patients with early cancer [mucosal or submucosal 1 (SM1)
      cancer and no lymph node metastasis (N0)] in the middle or lower third of stomach
      (or both) who were either not eligible for endoscopic excision of gastric mucosa
      or for partial gastric excision in the mucosa = 3.5 cm or SM1 5.5 cm, or further
      in distance from the anal margin of the cancer to the pyloric sphincter. Cases in
      which the remnant stomach would become one-third or less of the original size
      were also applied. During excision with lymph nodes, the hepatic and celiac
      branches bifurcating from the anterior and posterior trunks of the vagal nerve
      were preserved. The antrum was severed 1.5 cm from the pyloric sphincter,
      preserving the arteria supraduodenalis. The substitute stomach was created as a 5
      cm jejunal pouch with a 3 cm jejunal conduit for orthodromic peristaltic movement
      using an automatic suture instrument to complete a side-to-side anastomosis of
      the folded jejunum. The anal side of the gastric remnant was manually anastomosed
      with the jejunal J pouch, and anastomosis of the pyloric antrum with the jejunal
      conduit was manually completed by stratum anastomosis. Postoperatively, the
      procedure in group A alleviated gastrointestinal symptoms such as appetite loss,
      epigastric fullness, reflux esophagitis, early dumping syndrome, body weight
      loss, endoscopic reflux esophagitis, and endoscopic gastritis in the remnant
      stomach, postprandial stasis of the substitute stomach, and postgastrectomy
      cholecystolithiasis better than in group B. The results suggest that the proposed
      technique is a function-preserving gastric operation appropriate for preventing
      postgastrectomy disorder.

PMID- 15457357
TI  - True versus mild hyperthermia during isolated hepatic perfusion: effects on
      melphalan pharmacokinetics and liver function.
AB  - Hyperthermic antiblastic isolated hepatic perfusion (IHP) with melphalan has been
      recently proposed as an alternative therapeutic option for patients with
      unresectable liver tumors. Although melphalan-heat antiblastic synergism is at a
      maximum at temperatures higher than 41 degrees C, IHP has so far been performed
      in humans at lower temperatures. In this experimental work, we compared IHP under
      mild versus true hyperthermic conditions in terms of drug pharmacokinetics and
      liver function. Ten pigs were submitted to IHP with melphalan 1.5 mg/kg at a mean
      temperature of 40 degrees C (group A, n = 5) or 42 degrees C (group B, n = 5).
      After a 60-minute perfusion, a 15-minute washout was performed. Perfusate-to
      plasma leakage was monitored using scintigraphy. Throughout perfusion, samples
      from the systemic blood, perfusate, and liver parenchyma were obtained to measure
      melphalan concentrations. Liver function was assessed using standard blood tests
      and the indocyanine green-based test. No deaths related to the IHP procedure were
      recorded. All animals had transient liver function impairment, with all liver
      function test results returning to normal within the observation period. At
      histologic examination, liver damage was similar under both hyperthermic
      conditions. Melphalan levels in the perfusate were not significantly different in
      the two study groups (the mean perfusate/plasma area under the curve from 0 to 60
      minutes ratios were 463 and 501, respectively). These results correlated well
      with those obtained using the scintigraphic method. Liver drug concentrations
      remained unchanged after true hyperthermia IHP. Under true hyperthermic
      conditions, neither an increase in liver parenchyma toxicity nor changes in
      melphalan pharmacokinetics were observed. These findings support the use of true
      hyperthermia in the clinical setting to exploit fully the antitumor synergism
      between melphalan and heat.

PMID- 15457358
TI  - Effectiveness of endoscopic nasobiliary drainage for postoperative bile leakage
      after hepatic resection.
AB  - The effectiveness of endoscopic nasobiliary drainage (ENBD) for postoperative
      bile leakage after hepatic resection was investigated retrospectively. Between
      1997 and 2002 a series of 486 hepatectomies without biliary reconstruction were
      performed. Bile leakage was divided into two categories. Type A was defined as
      bile leakage communicating with the main bile tree fistulographically or
      endoscopic cholangiographically, and type B was bile leakage without such a
      patency of bile flow. Bile leakage developed in 31 patients (6.4%) (types A/B =
      16/15). Type A frequently occurred at the major Glisson's sheath. In contrast,
      most type B cases occurred at the peripheral bile duct at the cut surface of the
      liver. Among the type A patients, 10 of 11 were effectively treated with ENBD.
      For the type B patients, 12 of 15 patients were successfully treated with
      intraabdominal drainage via surgical drains inserted during the operation or
      percutaneous tubes newly inserted for biliary fluid collection. ENBD was
      effective in two of three type B patients. The duration of bile leakage
      significantly shortened after initiation of ENBD in type A patients (15.3 +/- 6.9
      vs. 25.8 +/- 13.2 days, p < 0.05). The classification based on communication with
      the main bile tree is useful for determining therapeutic strategy. Type A leakage
      has a good indication for ENBD, whereas type B can be treated with intraabdominal
      drainage in most cases, although ENBD may be effective in some intractable type B
      cases. It is preferable to initiate ENBD as early as possible to shorten the
      duration of bile leakage and the subsequent hospital stay.

PMID- 15457359
TI  - Hepatitis C virus infection is a risk factor for tumor recurrence after resection
      of small hepatocellular carcinomas.
AB  - Hepatocellular carcinoma (HCC) is closely associated with chronic hepatitis B or
      C virus (HBV, HCV) infection. Tumor recurrence frequently occurs after surgical
      resection and may adversely affect the outcome. This study aimed to investigate
      the effect of viral hepatitis in association with HCC recurrence after resection.
      A total of 248 patients [HBV in 165, HCV in 44, dual HBV+HCV in 15, and non-B non
      C (NBNC) in 24] who underwent curative resection for HCC were included. The
      cumulative recurrence rate was compared according to the etiology of the
      underlying hepatitis and was stratified by tumor size and other clinicopathologic
      parameters. Altogether, 116 patients (47%) had a tumor recurrence within 17 +/-
      11 months after resection. No significant difference in recurrence was noted
      among the four groups of patients (HBV, HCV, HBV+HCV, NBNC) ( p = 0.248).
      Persistent hepatitis was more common in the HCV group ( p < 0.001) after
      resection. Among the 157 patients with a small (= 5 cm) tumor, the recurrence
      rate was significantly higher in the HCV group than in the HBV, HBV+HCV, and NBNC
      groups ( p = 0.036). Cox multivariate analysis showed that HCV infection
      [relative risk (RR) 4.4, 95% confidence interval (CI) 1.3-14.8, p = 0.018] and
      vascular invasion (RR 3.2, 95% CI 1.2-8.9, p = 0.044) were independent predictors
      of tumor recurrence. Stratified analysis in other parameters did not show
      significant differences in terms of tumor recurrence among the four virologic
      groups ( p > 0.1 for all parameters). In conclusion, patients with small HCCs and
      concurrent HCV infection are at a high risk of tumor recurrence after resection.

PMID- 15457360
TI  - Prognostic impact of Fas ligand on hepatocellular carcinoma after hepatectomy.
AB  - The expression of Fas ligand on tumor cells may counterattack the host's immunity
      and worsen the prognosis. Knowledge of the prognostic impact of Fas ligand on
      patients with hepatocellular carcinoma (HCC) after hepatectomy is still limited.
      Fas ligand expression in HCCs was examined in 59 patients who underwent
      hepatectomy for HCC. The prognosis was analyzed and correlated to the expression
      of Fas ligand. Expression of Fas ligand was detected by immunohistochemical
      staining in 27 of the 59 HCCs (45.8%). The Fas ligand was expressed in only a
      small number of cancer cells. However, even though only a few cancer cells
      expressed it, the prognosis for patients whose HCCs showed Fas ligand expression
      was worse than that for patients with an HCC without Fas ligand expression. The
      mean disease-free survival was only 10.83 +/- 1.90 months when HCCs expressed Fas
      ligand compared with 43.51 +/- 7.02 months for those without Fas ligand
      expression ( p = 0.0007). The overall patient survival was 28.34 +/- 4.08 months
      when the HCC expressed Fas ligand compared with 55.31 +/- 5.37 months for HCC
      without Fas ligand expression ( p = 0.0003). The expression of Fas ligand did not
      correlate with the presentation of other prognostic factors. Fas ligand
      expression is thus an independent prognostic factor for HCC. Thus the HCC
      expressing Fas ligand has a worse prognosis than the HCC without Fas ligand
      expression.

PMID- 15457361
TI  - Surgical and endovascular procedures for treating isolated iliac artery
      aneurysms: ten-year experience.
AB  - Characteristics of atherosclerotic isolated iliac artery aneurysms (IAAs) and
      various strategies for their treatment were assessed retrospectively. The
      computerized medical records of 18 patients who underwent surgical or
      endovascular treatment of an IAA during the 10 years from April 1993 to March
      2003 at our university hospital were reviewed to obtain information on patient
      demographics, risk factors, type of IAA treatment, and outcome. Additional data
      were obtained by mail and telephone. Patients with an IAA were compared with 168
      patients treated for an abdominal aortic aneurysm (AAA) also at our institution.
      Early in the series of isolated IAA repairs, patients underwent prosthetic graft
      interposition ( n = 7) or thromboexclusion ( n = 4). Subsequently, patients had
      either endovascular thromboembolization ( n = 4) or endovascular
      thromboembolization with femorofemoral crossover bypass ( n = 3). No
      perioperative deaths occurred in the series. Deep venous thrombosis developed
      postoperatively in one patient; there were no other serious complications. The
      cumulative patency rate for the implanted interposition grafts during the mean
      observation time of 5.5 years was 100%. No endoleakage was observed after the
      endovascular procedures. In the long-term, five patients died of causes unrelated
      to the IAA treatment. A statistical analysis revealed no significant differences
      between the IAA group and the AAA group with respect to atherosclerotic risk
      factors. In conclusion, open surgical procedures to repair isolated IAAs
      generally have a good outcome, although the risk of injury to adjacent iliac
      veins remains. Endovascular treatments appear to have some advantages, but
      studies including long-term follow-up are needed to assess the efficacy and
      durability of prosthetic grafts used for these procedures.

PMID- 15457362
TI  - Long-term results of through-knee amputation with dorsal musculocutaneous flap in
      patients with end-stage arterial occlusive disease.
AB  - A modified technique of knee joint disarticulation using a dorsal
      musculocutaneous flap of the gastrocnemius muscle was first described in 1985.
      The operative results in 66 patients (33 women, 33 men; mean age 66.7 +/- 11.3
      years, range 42-93 years) with gangrene due to peripheral vascular disease with
      69 knee disarticulations are reported. After a mean survival period of 35.2
      months (0-116 months), 88% ( n = 58) of the patients had died owing to
      cardiopulmonary reasons. The in-hospital 48-day mortality was 9%. Nine patients
      (14%) underwent reamputation at the above-knee level, and five patients underwent
      operative revision of the soft tissue. After discharge from the hospital, 35 of
      60 patients (58%) were able to walk with the aid of a prosthesis. We conclude
      that knee disarticulation with the use of a myocutaneous gastrocnemius flap is a
      safe, functionally acceptable operative method in high risk vascular patients.

PMID- 15457363
TI  - Venous thromboembolism prophylaxis after head and spinal trauma: intermittent
      pneumatic compression devices versus low molecular weight heparin.
AB  - Although there are alternative methods and drugs for preventing venous
      thromboembolism (VTE), it is not clear which modality is most suitable and
      efficacious for patients with severe (stable or unstable) head/spinal injures.
      The aim of this study was to compare intermittent pneumatic compression devices
      (IPC) with low-molecular-weight heparin (LMWH) for preventing VTE. We
      prospectively randomized 120 head/spinal traumatized patients for comparison of
      IPC with LMWH as a prophylaxis modality against VTE. Venous duplex color-flow
      Doppler sonography of the lower extremities was performed each week of
      hospitalization and 1 week after discharge. When there was a suspicion of
      pulmonary embolism (PE), patients were evaluated with spiral computed tomography.
      Patients were analyzed for demographic features, injury severity scores,
      associated injuries, type of head/spinal trauma, complications, transfusion, and
      incidence of deep venous thrombosis (DVT) and PE. Two patients (3.33%) from the
      IPC group and 4 patients (6.66%) from the LMWH group died, with their deaths due
      to PE. Nine other patients also succumbed, unrelated to PE. DVT developed in 4
      patients (6.66%) in the IPC group and in 3 patients (5%) in the LMWH group. There
      was no statistically significant difference regarding a reduction in DVT, PE, or
      mortality between groups ( p = 0.04, p > 0.05, p > 0.05, respectively). IPC can
      be used safely for prophylaxis of VTE in head/spinal trauma patients.

PMID- 15457364
TI  - Palliation of malignant gastroduodenal obstruction with open surgical bypass or
      endoscopic stenting: clinical outcome and health economic evaluation.
AB  - Gastroduodenal outlet obstruction is a complication of advanced gastrointestinal
      malignant disease. In the past it was usually treated by an open surgical bypass
      procedure. During the last decade, endoscopic self-expandable stents (SEMS) have
      been used. The aim of this study was to compare these two palliative strategies
      concerning clinical outcome and health economy. A series of 36 patients with
      incurable malignant disease and gastroduodenal outlet obstruction syndrome were
      treated in a prospective study. According to the attending hospital and
      endoscopist on duty, 21 of the 36 patients were endoscopically treated with SEMS
      and 15 underwent an open surgical gastroenteroanastomosis. Health economic
      evaluation was based on the monetary charges for each patient associated with the
      procedure, postoperative care, and hospital stay. The hospital stay was 7.3 days
      for the stented group compared with 14.7 days for the open surgery group ( p >
      0.05). The survivals were 76 and 99 days, respectively (NS). In the stented group
      all 15 patients (100%) alive after 1 month were able to eat or drink, and 11
      (73%) of them tolerated solid food. In the surgical bypass group,9 out of 11
      (81%) patients alive after 1 month could eat or drink, and 5 of them (45%) could
      eat solid food. The mean charges (U.S. dollars) during the hospital stay were
      $7215 for the stented group and $10,190 for the open surgery group ( p < 0.05).
      Palliation of the gastroduodenal obstruction in patients with malignant disease
      were at least as good, and the charges were lower for the endoscopic stenting
      procedure than for an open surgical bypass.

PMID- 15457365
TI  - Desmoplastic reaction influences pancreatic cancer growth behavior.
AB  - Connective tissue growth factor (CTGF), which is regulated by transforming growth
      factor-ss (TGFss), has recently been implicated in the pathogenesis of fibrotic
      diseases and tumor stroma. Inasmuch as generation of desmoplastic tissue is
      characteristic for pancreatic cancer, it is not known whether it gives pancreatic
      cancer cells a growth advantage or is a reaction of the body to inhibit cancer
      cell progression. In the present study we analyzed the expression and
      localization of CTGF and evaluated whether it influences the prognosis of
      pancreas cancer. Tissue samples were obtained from 25 individuals (6 women, 19
      men) undergoing pancreatic resection for pancreatic cancer. Tissue samples from
      13 previously healthy organ donors (5 women, 8 men) served as controls.
      Expression of CTGF was studied by Northern blot analysis. In situ hybridization
      and immunohistochemistry localized the respective mRNA moieties and proteins in
      the tissue samples. Northern blot analysis revealed that pancreatic cancer tissue
      samples exhibited a 46-fold increase in CTGF mRNA expression ( p < 0.001) over
      that of normal controls. In vitro studies confirmed that pancreatic stellate
      cells are the major source of CTGF mRNA expression and revealed a large variance
      in basal and TGFss-induced CTGF expression in cultured pancreatic cancer cells.
      This could also be confirmed by in situ hybridization, indicating that CTGF mRNA
      signals were located principally in fibroblasts, with only weak signals in the
      cancer cells. High CTGF mRNA levels in the tissue samples correlated with better
      tumor differentiation ( p < 0.03). In addition, patients whose tumors exhibited
      high CTGF mRNA levels (> onefold increase above normal controls) lived
      significantly longer than those whose tumors expressed low CTGF mRNA levels (none
      to onefold) ( p < 0.04 multivariate analysis). Our present data indicate that
      CTGF, as a downstream mediator of TGFss, is overexpressed in connective tissue
      cells and to a lesser extent in pancreatic cancer cells. Because patients with
      high CTGF mRNA expression levels have a better prognosis, our findings indicate
      that the desmoplastic reaction provides a growth disadvantage for pancreatic
      cancer cells.

PMID- 15457366
TI  - Cell-specific cytotoxicity of human pancreatic adenocarcinoma cells using rat
      insulin promoter thymidine kinase-directed gene therapy.
AB  - The formation of a normal pancreas and the activation of insulin production are,
      in part, dependent on the expression and activation of the pancreatic duodenal
      homeobox gene 1 (PDX-1). The expression of PDX-1 also has been detected in
      various human pancreatic ductal adenocarcinoma (PDA) cell lines. This has made it
      possible to generate a cancer cell-specific gene expression system to treat human
      pancreatic cancer. In this study, we have developed a cell-specific cytotoxic
      model of PDA cells using the expression of herpes simplex virus thymidine kinase
      (TK) under the control of the rat insulin promoter (RIP-TK). We have shown that
      the cell-specific cytotoxicity in human PDA cells depends on the presence of PDX
      1. Our results also demonstrate that in vivo PDA-specific cytotoxicity can be
      achieved with RIP-TK using an intraperitoneal liposomal gene delivery method
      followed by a short period of ganciclovir treatment in severe combined
      immunodeficient (SCID) mice. Furthermore, PDX-1 protein was found in all six
      freshly isolated human pancreas cancer specimens and two liver metastasis samples
      that were group-tested, suggesting the feasibility of using RIP-TK gene therapy
      in humans. This study may provide an alternative strategy for the future
      treatment of pancreatic cancer.

PMID- 15457367
TI  - Dependence of positive effects of granulocyte colony-stimulating factor on the
      antibiotic regimen: evaluation in rats with polymicrobial peritonitis.
AB  - We tested the hypothesis that the ability of granulocyte colony-stimulating
      factor (G-CSF) to prevent death from fecal peritonitis is influenced by the
      composition of the antibiotic regimen with which it is administered. We used a
      rodent model of polymicrobial peritoneal contamination and infection and the
      concept of clinical modeling randomized trials (CMRTs), which includes the
      conditions of randomized, clinical trials and complex clinical interventions
      (e.g., anesthesia, volume substitution, antibiotics, surgery, postoperative
      analgesia). With the peritonitis model we obtained a mortality dose-response
      curve that was sensitive to antibiotic prophylaxis. G-CSF was most efficacious
      when it was administered both prophylactically and after the onset of
      peritonitis. Cefuroxime/metronidazole, ofloxacin/metronidazole, and
      amoxicillin/clavulanate improved survival in combination with G-CSF best, whereas
      cefotaxime or ceftriaxone with and without metronidazole did not. G-CSF
      administration was associated with improved polymorphonuclear neutrophil
      phagocytosis and enhanced bacterial clearance. Pro-inflammatory cytokine release
      (tumor necrosis factor-a, interleukin-6, macrophage inflammatory protein-2) was
      decreased in plasma and in the peritoneal fluid. Their expression was lowered in
      various organs on the protein and mRNA level. The results were used to design a
      clinical trial to test the ability of G-CSF to prevent serious infections in
      patients with colorectal cancer surgery. In this trial G-CSF application and
      antibiotic prophylaxis were performed with the most effective scheduling and
      combinations (cefuroxime/metronidazole and ofloxacin/metronidazole) as defined
      here.

PMID- 15457369
TI  - Nuclear envelope: nanoarray responsive to aldosterone.
AB  - Signalling between cytosol and nucleus is mediated by nuclear pores. These
      supramolecular complexes represent intelligent nanomachines regulated by a wide
      spectrum of factors. Among them, steroid hormones specifically interact with the
      pores and thus modify ion conductivity and macromolecule permeability of the
      nuclear envelope. In response to aldosterone the pores undergo dramatic changes
      in conformation, changes that depend on the nature of the transported cargo. Such
      changes can be imaged at the nanometer scale by using atomic force microscopy.
      Furthermore, steroid-induced macromolecule transport across the nuclear envelope
      causes osmotic water movements and nuclear swelling. Drugs that interact with
      intracellular steroid receptors (spironolactone) or with plasma membrane sodium
      channels (amiloride) inhibit swelling. Steroid hormone action is blocked when
      nuclear volume changes are prevented. This is shown in frog oocytes and human
      endothelial cells. In conclusion, nuclear pores serve as steroid-sensitive gates
      that determine nuclear activity.

PMID- 15457370
TI  - Transient permeability leak of nuclear envelope induced by aldosterone.
AB  - The mineralocorticoid hormone aldosterone controls fluid and electrolyte
      transport in target cells of the kidney and the cardiovascular system. Classic
      genomic aldosterone action involves the activation of cytosolic mineralocorticoid
      receptors and translocation into the cell nucleus where specific transcription
      processes are initiated. A key barrier of the intracellular signalling pathway is
      the nuclear envelope, which physically separates the nucleoplasm from the
      cytoplasm. It was shown recently that aldosterone changes ion conductivity of the
      nuclear envelope mediated by nuclear pore complexes. The latter are
      supramolecular nanomachines responsible for import and export of inorganic ions
      and macromolecules. The aim of the present study was to test whether aldosterone
      changes the macromolecule permeability of the nuclear envelope. Aldosterone
      responsive Xenopus laevis oocytes were used as a model system. We isolated the
      cell nuclei at defined times after hormone injection. By means of confocal
      fluorescence microscopy and fluorescence-labelled dextrans we evaluated passive
      macromolecule import and export in isolated nuclei. 10 minutes after aldosterone
      injection nuclear envelope permeability of 10 kD dextran was found sharply
      increased. At the same time cell nuclei were found swollen by about 28%. Changes
      in nuclear volume and nuclear envelope permeability lasted 5 to 15 minutes and
      could be inhibited by the mineralocorticoid receptor blocker spironolactone. We
      conclude that aldosterone transiently changes the barrier function of the nuclear
      envelope. This short-lasting permeability change signals the start of a sustained
      transcription process that follows in response to steroids.

PMID- 15457371
TI  - Conductive and kinetic properties of connexin45 hemichannels expressed in
      transfected HeLa cells.
AB  - Human HeLa cells transfected with mouse connexin Cx45 were used to examine the
      conductive and kinetic properties of Cx45 hemichannels. The experiments were
      carried out on single cells using a voltage-clamp method. Lowering the [Ca2+]o
      revealed an extra current. Its sensitivity to extracellular Ca2+ and gap junction
      channel blockers (18alpha-glycyrrhetinic acid, palmitoleic acid, heptanol), and
      its absence in non-transfected HeLa cells suggested that it is carried by Cx45
      hemichannels. The conductive and kinetic properties of this current, Ihc, were
      determined adopting a biphasic pulse protocol. Ihc activated at positive Vm and
      deactivated partially at negative Vm. The analysis of the instantaneous Ihc
      yielded a linear function ghc,inst = f(Vm) with a hint of a negative slope
      (ghc,inst: instantaneous conductance). The analysis of the steady-state Ihc
      revealed a sigmoidal function ghc,ss=f(Vm) best described with the Boltzmann
      equation: Vm,0= -1.08 mV, ghc,min=0.08 (ghc,ss: steady-state conductance; Vm,0:
      Vm at which ghc,ss is half-maximally activated; ghc,min: minimal conductance;
      major charge carriers: K+ and Cl-). The ghc was minimal at negative Vm and
      maximal at positive Vm. This suggests that Cx45 connexons integrated in gap
      junction channels are gating with negative voltage. Ihc deactivated exponentially
      with time, giving rise to single time constants, taud. The function taud = f(Vm)
      was exponential and increased with positive Vm (taud=7.6 s at Vm=0 mV). The
      activation of Ihc followed the sum of two exponentials giving rise to the time
      constants, taua1 and taua2. The function taua1=f(Vm) and taua2 = f(Vm) were bell
      shaped and yielded a maximum of congruent with 0.6 s at Vm congruent with -20 mV
      and congruent with 4.9 s at Vm congruent with 15 mV, respectively. Neither taua1
      =f(Vm) nor taua2 = f(Vm) coincided with taud=f(Vm). These findings conflict with
      the notion that activation and deactivation follow a simple reversible reaction
      scheme governed by first-order voltage-dependent processes.

PMID- 15457372
TI  - Regulation of muscle Cav1.1 channels by long-term depolarization involves
      proteolysis of the alpha1s subunit.
AB  - The effects of long-term depolarization on frog skeletal muscle Cav1.1 channels
      were assessed. Voltage-clamp and Western-blot experiments revealed that long-term
      depolarization brings about a drastic reduction in the amplitude of currents
      flowing through Cav1.1 channels and in the levels of the alpha1s subunit, the
      main subunit of muscle L-type channels. The decline of both phenomena was
      prevented by the action of the protease inhibitors E64 (50 microM) and leupeptin
      (50 microM). In contrast, long-term depolarization had no effect on beta1, the
      auxiliary subunit of alpha1s. The levels of mRNAs coding the alpha1s and the
      beta1 subunits were measured by RNase protection assays. Neither the content of
      the alpha1s nor the beta1 subunit mRNAs were affected by long-term
      depolarization, indicating that the synthesis of Cav1.1 channels remained
      unaffected. Taken together, our experiments suggest that the reduction in the
      amplitude of membrane currents and in the alpha1s subunit levels is caused by
      increased degradation of this subunit by a Ca2+-dependent protease.

PMID- 15457373
TI  - Catecholamine-induced regulation in vitro and ex vivo of intralymphocyte ionized
      magnesium.
AB  - Despite the importance of the adrenergic activity and of the metabolism of
      magnesium in some important cardiovascular pathologies, very little is known
      about how intracellular ionized magnesium (Mgi2+) is regulated by catecholamines.
      We made an in-vitro study of the variations in the concentration of ionized
      magnesium in human lymphocytes using the fluorescent probe furaptra in response
      to different catecholamines. We also made an ex-vivo study of the changes in
      intracellular ionized magnesium in lymphocytes in 20 subjects with essential
      arterial hypertension, 10 treated with 120 mg/d of propranolol and 10 with
      placebo. Norepinephrine and isoproterenol significantly decrease Mgi2+ and this
      effect is blocked by beta-blockers but not by alpha-blockers. The EC50 of the
      effect of norepinephrine is within the range of concentrations physiologically
      present in plasma. The substitution of extracellular sodium with choline blocks
      the decrease in intracellular ionized magnesium induced by norepinephrine, which
      leads us to suppose that the magnesium-reducing effect of catecholamines is a
      result of the activation of a Na+-Mg2+ exchanger. We were not able to demonstrate
      any change in intracellular ionized magnesium after 1 and 17 days of active
      treatment in essential hypertensives. The impossibility of demonstrating ex vivo
      the mechanism of catecholamine-mediated regulation that is evident in vitro is
      perhaps due to our experimental conditions or to substances which in vivo inhibit
      the action of the catecholamines on magnesium, such as insulin and/or glucose.

PMID- 15457374
TI  - Regulation of D-fructose transporter GLUT5 in the ileum of spontaneously
      hypertensive rats.
AB  - Abnormalities in carbohydrate metabolism and the insulin resistance status have
      been associated with hypertension. We have previously described alterations in
      the sodium-coupled sugar absorption in an experimental model of hypertension; in
      the present work, we studied the regulation of the sodium-independent, GLUT5
      facilitated D-fructose intestinal transport in this pathology. Spontaneously
      hypertensive rats (SHR) and their normotensive, genetic control Wistar-Kyoto
      (WKY) rats, were used. Kinetic studies, carried out in ileal brush-border
      membrane vesicles (BBMVs), revealed a significant reduction (P < 0.05) in the
      maximal rate of transport (Vmax) for D-fructose in SHR, which, on the other hand,
      showed unaltered values for the Michaelis constant (Km) and the diffusion
      constant (Kd). Immunoblotting analysis revealed the existence of lower (P< 0.05)
      levels of GLUT5 in apical membranes from SHR, this reduction being similar to
      that of Vmax. Similarly, Northern blot studies on the abundance of GLUT5 mRNA
      from ileal enterocytes showed a decrease (P< 0.05) in hypertensive rats,
      following the same pattern mentioned above. Therefore, the impaired D-fructose
      intestinal absorption is another feature of SHR, and this decrease in D-fructose
      uptake correlates with a reduction in the abundance of the apical GLUT5
      transporter, which is controlled at a transcriptional level.

PMID- 15457375
TI  - Reusing disposal laparoscopic instruments.

PMID- 15457376
TI  - Laparoscopic resection of colon Cancer: consensus of the European Association of
      Endoscopic Surgery (EAES).
AB  - BACKGROUND: The European Association of Endoscopic Surgery (EAES) initiated a
      consensus development conference on the laparoscopic resection of colon cancer
      during the annual congress in Lisbon, Portugal, in June 2002. METHODS: A
      systematic review of the current literature was combined with the opinions, of
      experts in the field of colon cancer surgery to formulate evidence-based
      statements and recommendations on the laparoscopic resection of colon cancer.
      RESULTS: Advanced age, obesity, and previous abdominal operations are not
      considered absolute contraindications for laparoscopic colon cancer surgery. The
      most common cause for conversion is the presence of bulky or invasive tumors.
      Laparoscopic operation takes longer to perform than the open counterpart, but the
      outcome is similar in terms of specimen size and pathological examination.
      Immediate postoperative morbidity and mortality are comparable for laparoscopic
      and open colonic cancer surgery. The laparoscopically operated patients had less
      postoperative pain, better-preserved pulmonary function, earlier restoration of
      gastrointestinal function, and an earlier discharge from the hospital. The
      postoperative stress response is lower after laparoscopic colectomy. The
      incidence of port site metastases is <1%. Survival after laparoscopic resection
      of colon cancer appears to be at least equal to survival after open resection.
      The costs of laparoscopic surgery for colon cancer are higher than those for open
      surgery. CONCLUSION: Laparoscopic resection of colon cancer is a safe and
      feasible procedure that improves short-term outcome. Results regarding the long
      term survival of patients enrolled in large multicenter trials will determine its
      role in general surgery.

PMID- 15457377
TI  - Management of major bile duct injuries after laparoscopic cholecystectomy.
AB  - BACKGROUND: The aim of this study was to analyze the presentation,
      characteristics, related investigation, and treatment results of major bile duct
      injuries (MBDI) after laparoscopic cholecystectomy (LC). METHODS: We performed a
      retrospective analysis of 27 patients who were treated between January 1995 and
      December 2002 for MBDI after LC at a single unit in a tertiary center. Major bile
      duct injury was defined according to the Strasberg classification. All patients
      underwent magnetic resonance cholangiography (MRC), percutaneous transhepatic
      cholangiography (PTC), or endoscopic retrograde cholangiopancreatography (ERCP)
      to delineate the biliary anatomy and assess the level of injury. On the basis of
      the cholangiographic findings, all patients underwent Roux-en-Y
      hepaticojejunostomy after a waiting period of 8-12 weeks. RESULTS: A total of 29
      hepaticojejunostomies were performed in 27 patients. Seventeen patients (63%)
      presented with biliary fistula and ascites; 10 (27%) presented with obstructive
      jaundice. In 14 patients (52%) the MBDI was identified during the LC. Twenty
      patients (74%) had undergone one or more procedure before referral. Eight
      patients (30%) had E1, five patients (18.5%) had E2, nine patients (33%) had E3,
      and five patients (18.5%) had E4 injury. Two patients had early anastomotic
      stricture, for which redo hepaticojejunostomy with access loop was performed.
      CONCLUSIONS: Major bile duct injury after LC commonly presents with biliary
      fistula and ascites. High-injuries are common after LC. Hepaticojejunostomy
      repair yields excellent results in these cases.

PMID- 15457378
TI  - Peritoneal gallstones following laparoscopic cholecystectomy: incidence,
      complications, and management.
AB  - BACKGROUND: Gallstone spillage during laparoscopic cholecystectomy (LC) is a
      common intraoperative event. Although gallstones left in the peritoneal cavity
      were initially considered harmless, a significant number of complications have
      been reported. Our aim was to quantify the likelihood, and to document the range,
      of subsequent complications. METHODS: A Medline search from 1987 to January 2003
      was performed. Articles with more than 500 LCs that quantified the frequency of
      complications due to peritoneal gallstones were reviewed, as were representative
      case studies of different stated complications. RESULTS: Six studies, covering
      18,280 LCs, were found. The incidence of gallbladder perforation was 18.3%, that
      of gallstone spillage was 7.3%, and that of unretrieved peritoneal gallstones was
      estimated to be 2.4%. There were 27 patients with complications. The likelihood
      of a complication when gallstone spillage occurred was 2.3%, which increased to
      7.0% when unretrieved peritoneal gallstones were documented. CONCLUSION: Spilt
      gallstones have a small but quantifiably real risk of causing a wide range of
      significant postoperative problems.

PMID- 15457379
TI  - Video-assisted thyroidectomy for Graves' disease: report of a preliminary
      experience.
AB  - BACKGROUND: Ever since the introduction of video-assisted thyroidectomy (VAT),
      Graves' disease has represented a contraindication. This study aimed to
      demonstrate that VAT can be proposed also for Graves' disease. METHODS: From
      January 2002 to March 2003, 21 patients (20 women and 1 man) with Graves' disease
      underwent VAT. One patient showed positive test results for gene RET. The mean
      age of the patients was 36.4 years. RESULTS: No conversions of procedure were
      necessary. The mean operative time was 56.9 min. The RET-positive patient
      underwent total thyroidectomy and central compartment lymphadenectomy.
      Postoperative bleeding occurred in the patient with the largest gland. Histology
      showed goiter in 18 cases, medullary carcinoma in 1 case, and papillary carcinoma
      in 2 cases. No cases of vocal cord palsy but three cases of transient
      hypocalcemia were registered. CONCLUSIONS: Graves' disease can be treated safely
      using VAT only if selection criteria are carefully respected. The young age of
      the patients with this disease encourages us to propose VAT for its good cosmetic
      and postoperative outcome.

PMID- 15457380
TI  - Laparoscopic versus open total mesorectal excision with anal sphincter
      preservation for low rectal cancer.
AB  - BACKGROUND: The Laparoscopic approach has been applied to colorectal surgery for
      many years; however, there are only a few reports on laparoscopic low and
      ultralow anterior resection with construction of coloanal anastomosis. This study
      compares open versus laparoscopic low and ultralow anterior resections, assesses
      the feasibility and efficacy of the laparoscopic approach of total mesorectal
      excision (TME) with anal sphincter preservation (ASP), and analyzes the short
      term results of patients with low rectal cancer. METHODS: We analyzed our
      experience via a prospective, randomized control trail. From June 2001 to
      September 2002, 171 patients with low rectal cancer underwent TME with ASP, 82 by
      the laparoscopic procedure and 89 by the open technique. The lowest margin of
      tumors was below peritoneal reflection and 1.5-8 cm above the dentate line (1.5
      4.9 cm in 104 cases and 5-8 cm in 67 cases). The grouping was randomized.
      RESULTS: Results of operation, postoperative recovery, and short-term oncological
      follow-up were compared between 82 laparoscopic procedures and 89 controls who
      underwent open surgery during the same period. In the laparoscopic group, 30
      patients in whom low anterior resection was performed had the anastomosis below
      peritoneal reflection and more than 2 cm above the dentate line, 27 patients in
      whom ultralow anterior resection was performed had anastomotic height within 2 cm
      of the dentate line, and 25 patients in whom coloanal anastomosis was performed
      had the anastomosis at or below the dentate line. In the open group, the numbers
      were 35, 27, and 27, respectively. There was no statistical difference in
      operation time, administration of parenteral analgesics, start of food intake,
      and mortality rate between the two groups. However, blood loss was less, bowel
      function recovered earlier, and hospitalization time was shorter in the
      laparoscopic group. CONCLUSION: Totally laparoscopic TME with ASP is feasible,
      and it is a minimally invasive technique with the benefits of much less blood
      loss during operation, earlier return of bowel function, and shorter
      hospitalization.

PMID- 15457381
TI  - The AESOP robot system in laparoscopic surgery: increased risk or advantage for
      surgeon and patient?
AB  - BACKGROUND: The aim of this study was to examine the advantages and risks of the
      Automated Endoscopic System for Optical Positioning (AESOP) 3000 robot system
      during uncomplicated laparoscopic cholecystectomies or laparoscopic hernioplasty.
      METHODS: In a randomized study, we examined two groups of 120 patients each with
      the diagnosis cholecystolithiasis respectively the unilateral inguinal hernia. We
      worked with the AESOP 3000, a robotic arm system that is voice-controlled by the
      surgeon. The subjective and objective comfort of the surgeon as well as the
      course and length of the operation were measured. RESULTS: The robot-assisted
      operations required significantly longer preparation and operation times. With
      regard to the necessary commands and manual camera corrections, the assistant
      group was favored. The same was true for the subjective evaluation of the
      surgical course by the surgeon. CONCLUSIONS: Our study showed that the use of
      AESOP during laparoscopic cholecystectomy and hernioplasty is possible in 94% of
      all cases. The surgeon must accept a definite loss of comfort as well as a
      certain loss of time against the advantage of saving on personnel.

PMID- 15457382
TI  - The learning curve for a colonoscopy simulator in the absence of any feedback: no
      feedback, no learning.
AB  - BACKGROUND: The hypothesis of this study is that working on the simulator without
      a structured feedback does not change performance; hence, any effects shown after
      structured feedback would amount to useful learning of the procedure. The aim was
      to investigate the learning curve for the HT Immersion Medical Colonoscopy
      Simulator without any structured feedback. This could then be potentially applied
      to validate the learning curve on the simulator when structured feedback is
      provided. There are no previous studies on this matter. METHODS: Candidates were
      asked to perform colonoscopy on the HT Immersion Medical Colonoscopy Simulator.
      Modules 3 and 4 were used at random. In total, each candidate was asked to
      perform five consecutive virtual colonoscopies on the same module. These five
      episodes were collectively referred to as one trial. A time result of 3,600 sec
      (1 h) was used to denote perforation. No guidance or feedback was given to
      candidates before, during, or after each procedure. A total of 26 postgraduate
      doctors were recruited, including nine research fellows, five preregistration
      house officers, six specialist registrars, and six consultants. Fourteen
      candidates recorded five attempts each (i.e., one trial each) on the same module
      of the colonoscopy simulator (14 trials over 70 episodes). Another 12 candidates
      recorded five attempts (i.e., one trial each) on two modules of the colonoscopy
      simulator (24 trials over 120 episodes). Hence, 190 episodes were recorded in
      total, representing 38 trials. RESULTS: There was no improvement in performance
      on the simulator from first attempt to the fifth in the absence of feedback. If
      there was any initial gain in any measurable outcome, this was lost in subsequent
      attempts indicating lack of learning. The outcomes measured included time taken
      to complete the test, percentage of the mucosa visualized, depth of the
      instrument inserted, and the path length used. The results were statistically
      significant for all outcomes. CONCLUSIONS: This study demonstrates that in the
      absence of feedback, it is not possible to improve performance on the HT
      Immersion Medical Colonoscopy Simulator. Thus, there is no learning curve for the
      machine. The information from this study is vital for using the simulators in
      training and assessment because any improvement in learning curves shown after
      training on simulators can be presumed to be due to learning the procedure and
      not the simulator.

PMID- 15457383
TI  - Ergonomic aspects of five different types of laparoscopic instrument handles
      under dynamic conditions with respect to specific laparoscopic tasks: an
      electromyographic-based study.
AB  - BACKGROUND: The ergonomic deficiencies of various minimally invasive surgery
      (MIS) instrument handles are well-known. In the past, many studies have been
      performed to gain a better understanding of ergonomics in MIS. The current study
      investigates muscle strain during various dynamic tasks with different instrument
      handles. METHODS: Five different handle designs were tested: the axial handle
      (Aesculap), the vario handle (own model), multifunctional and ring handles (both
      Karl Storz), and the shank handle (Wilo). Ten subjects without any surgical
      training tested the following instrument functions: precise dynamic movement,
      rotation of the closed instrument, and simultaneous opening and closing of the
      effector. During these three trials, task performance (errors/duration) and the
      electromyographic activity of the hand and lower arm muscles were measured.
      RESULTS: Regarding the errors and the time required to carry out the tasks, the
      five handles showed similar results. The muscle activity was lowest for the
      precise dynamic movement task and highest during the rotation task. The axial
      handle required significantly more muscle activity than all other handles.
      CONCLUSION: On the basis of these data, it was possible to construct
      characteristic muscle activation patterns for each handle. However, these
      patterns were not task specific. Accordingly, they may form a basis to improve
      the ergonomics of MIS handles with regard to muscle strain.

PMID- 15457384
TI  - Laparoscopic navigation pointer for three-dimensional image-guided surgery.
AB  - BACKGROUND: The main drawback with the laparoscopic approach is that the surgeon
      is unable to palpate vessels, tumors, and organs during surgery. Furthermore, the
      laparoscope provides only surface view of organs. There is a need for more
      advanced visualizations that can enhance the view to include information below
      the surface of the organs for planning of the procedure and for control and
      guidance during treatment. METHODS: We propose three-dimensional (3D) navigation
      technology based on preoperatively acquired magnetic resonance or computed
      tomography data used in combination with a laparoscopic navigation pointer (LNP).
      The LNP has an attached position tracker that allows the surgeon to control the
      display of images interactively before and during surgery. This study evaluated
      the patient registration accuracy, the feasibility of image-based navigation and,
      qualitatively, the navigation precision in the retroperitoneum during
      laparoscopic surgery. RESULTS: This technology was used during the treatment of
      six patients (involving adrenalectomies and a neuroma protruding into the
      pelvis). An average patient registration accuracy of 6.90 mm was achieved. The
      precision during navigation in the retroperitoneum was, in some cases, better
      than the patient registration accuracy suggested. The technology helped the
      surgeons to understand better the anatomy and to locate blood vessels.
      CONCLUSIONS: In the reported cases, the LNP was a useful tool for image guidance
      in laparoscopic surgery, both for planning the surgical approach in detail and
      for guidance. The authors believe that adominal 3D image guidance using an LNP
      has a large potential for improving laparoscopic surgery, especially when vessels
      and anatomic relations may be difficult to identify using only a laparoscope.
      Accordingly, they believe this new technology could increase safety and make it
      easier for the surgeon to perform successful laparoscopic surgery.

PMID- 15457385
TI  - Laparoscopy-assisted distal gastrectomy for early gastric cancer in obese and
      nonobese patients.
AB  - BACKGROUND: Conventional open gastrectomy has been reported to result in
      increased morbidity in obese patients. To date, there has been no study
      evaluating laparoscopic gastrectomy in such patients; therefore, we assessed the
      short-term results of this procedure in a group of obese patients. METHODS: The
      study included 99 consecutive patients who underwent laparoscopy-assisted distal
      gastrectomy (LDG) for the cure of early gastric cancer. The patients were divided
      into two groups: obese (body mass index [BMI] > or =25.0, n = 16) and nonobese
      (BMI <25.0, n = 83). Patient characteristics, operative details, and
      postoperative outcomes were compared and analyzed. RESULTS: Patient
      characteristics, including age, sex, American Society of Anesthesiologists (ASA)
      status, and disease stage, were not different between obese and nonobese
      patients. Operating time was significantly longer in obese patients than in
      nonobese patients (271 vs 239 min, p < 0.05). However, there was no significant
      difference between obese and nonobese patients in time to first flatus (3.7 vs
      3.3 days), time to solid diet (6.3 vs 5.2 days), length of postoperative hospital
      stay (18.7 vs 17.9 days), or frequency of major (25% vs 16%) and minor (19% vs
      12%) postoperative complications. There were no conversions to conventional open
      surgery and no perioperative deaths. CONCLUSION: The only difference between our
      two study groups was that LDG required a longer operating time in obese patients;
      morbidity and length of hospital stay were not increased. Thus, we believe that
      LDG is likely to become the treatment of choice for obese patients with early
      gastric cancer.

PMID- 15457386
TI  - The effect of verapamil on the prevention of ischemia/reperfusion injury in the
      experimental retroperitoneoscopic donor nephrectomy model.
AB  - BACKGROUND: This study investigated the effect of intravenous administration of
      verapamil in prevention of the injury caused by free oxygen radicals generated in
      a rabbit retroperitoneoscopic donor nephrectomy model. METHODS: Twenty-four adult
      New Zealand rabbits were divided into four groups. In group I, balloon dissection
      of the left retroperitoneal space was performed. In group II, CO2 at 10 mmHg was
      applied for 3 hours after the balloon dissection. In group III, laparotomy was
      performed, the left renal pedicle was clamped for 3 min, and the clamp was
      removed 5 min before nephrectomy. In group IV, 2 min before the attempt 0.2 mg/kg
      verapamil was given intravenously, and the same procedure was employed as in
      group III. Nephrectomy was performed after each experiment. The concentrations of
      malonyl dialdehyde (MDA), reduced glutathione (GSH), and protein carbonyl content
      were measured in renal tissue samples as markers of oxidative stress. RESULTS:
      Pneumoretroperitoneum (Prp) promoted oxidative stress in renal tissues, with an
      increase of MDA and protein carbonyl content. The verapamil- pretreated group
      (group IV) showed statistical significantly lower values of MDA and protein
      carbonyl content when compared with group II and III (p < 0.05), whereas tissue
      GSH concentrations were unchanged in all groups. CONCLUSIONS: Our study showed
      that Prp causes increased oxidative stress in renal tissue. Warm ischemia lasting
      3 min did not exert an additive effect on Prp-associated oxidative stress.
      Verapamil reduces the oxidative stress markers caused by Prp.

PMID- 15457387
TI  - Long-term outcome after laparoscopic splenectomy related to hematologic
      diagnosis.
AB  - BACKGROUND: Laparoscopic splenectomy (LS) has been demonstrated as an effective
      and safe treatment for hematological disorders requiring spleen removal,
      especially in cases of normal-sized spleens. However, although results are
      promising, long-term outcome data are lacking. We reviewed our clinical
      experience with LS in a series of 255 cases, with particular attention to the
      long-term outcome related to the disease process requiring LS. METHODS: From
      February 1993 to October 2003, LS was attempted in 255 patients (100 males and
      155 females with a mean age of 45 +/- 19 years) and clinical information was
      recorded in a prospective database. Indications for splenectomy included
      idiopathic thrombocytopenic purpura (ITP) (n = 115), HIV-ITP (n = 9), Evans
      syndrome (n = 6), autoimmune hemolytic anemia (AIHA) (n = 13), hereditary
      spherocytosis (HS) (n = 19), hematologic malignancy (n = 66), thrombotic
      thrombocytopenic purpura (n = 1), and others (n = 26). Long-term postoperative
      follow-up evaluation was obtained through clinical notes, follow-up visits by the
      referring hematologist, and by phone interviews both with patients and with the
      referring hematologist. RESULTS: A total of 186 patients (73%) were available for
      a mean follow-up of 35 months (range, 1-104). Of the ITP patients, 87 (76%) were
      followed up, with a remission rate of 89% (complete remission in 75%). A similar
      remission rate was observed in ITP-HIV; in patients available for follow-up
      (78%), complete remission was achieved in 83%. In Evans, complete remission was
      achieved in all patients available for follow-up (67%). Clinical response for
      hemolytic disease ranged between 70% for AIHA and 100% for HS. In the malignant
      group, the late mortality rate was 22%. The mortality rate in the miscellaneous
      group was 5%. No cases of splenectomy-related sepsis occurred during follow-up.
      CONCLUSIONS: LS offers advantages for all types of splenic diseases requiring
      surgery. It provides not only good clinical short-term outcome but also
      satisfactory long-term hematological results.

PMID- 15457388
TI  - Commentary. Regarding the article "three dimensional view in endoscopic surgery"
      by N. Ishikawa et al.

PMID- 15457389
TI  - A simple technique for removal of the gallbladder during microlaparoscopic
      cholecystectomy.
AB  - With the advent of mini-instruments, laparoscopic cholecystectomies have been
      performed with two or three trocars instead of the standard four ports. However,
      removal of the gallbladder is a difficult aspect with these microlaparoscopic
      techniques. To remove the gallbladder through the 11-mm umbilical port, a 5-mm
      telescope should be used. However this telescope is not always available. Other
      techniques are suitable only for patients with limited or no inflammation of the
      gallbladder. An efficient, simple, and inexpensive technique is described that
      allows removal of the gallbladder through an 11-mm trocar without the need for a
      5-mm telescope. It permits removal of the specimen in acute suppurative or thick
      wall cholecystitis independently of the technique used.

PMID- 15457394
TI  - [Management of cardiovascular diseases].

PMID- 15457395
TI  - [Guideline-conforming interventional treatment of acute ST-segment elevation
      myocardial infarction in rural areas using network collaboration].
AB  - BACKGROUND AND OBJECTIVES: Therapy of acute myocardial infarction demands rapid
      and complete myocardial reperfusion. Primary percutaneous coronary intervention
      (PCI) performed is superior to thrombolytic therapy in reducing mortality, non
      fatal reinfarction and stroke, but is not available in rural Germany. PATIENTS
      AND METHODS: : From 8/2001 to 12/2002 322 patients with STEMI were treated by PCI
      with standardized therapeutic guidelines within a regional infarction-network
      comprising one interventional centre and 7 community hospitals without PCI
      facilities. 160 patients were relocated (transferred) from a community hospital
      without PCI facilities (transfer group, 63.4 yrs., 71.8 % men); 162 patients were
      admitted directly to the interventional centre (centre group, 61.7 yrs., 73.8 %
      men). The interval from onset of symptoms to first medical contact was 205
      minutes in the transfer group, and 195 minutes in the centre group. 7.8 % of the
      centre group and 7.2 % of the transfer group patients were in cardiogenic shock.
      95 % of patients have completed a 6-month's follow-up. RESULTS: In the transfer
      group median transportation time to PCI was 54 minutes. PCI of the infarct
      related artery (IRA) was performed in 95.1 % of transferred patients after
      transfer and in 94.1 % of patients with direct admission. In addition 96 % of all
      patients received a GP IIb/IIIa receptor inhibitor. In case of pre-interventional
      application of the GP IIb/IIIa receptor inhibitor 22.3 % of patients revealed
      normal (TIMI-3) flow of the IRA before PCI, compared to 14.9 % TIMI-3 flow with
      5000 IE Heparin/500 mg aspirin alone (p < 0.05). After PCI normalized flow in the
      IRA was documented in 87.5 % after direct admission and 86.3 % after transfer. No
      differences between groups were shown with respect to infarct size (transfer vs.
      centre: CK 2482 vs. 2481 U/I; CKMB 302 vs. 264 U/I), mortality (30 days: 5.3 vs.
      5.2 %, 6 months: 7.3 vs. 7.1 %); NYHA (1.41 vs. 1.43) and left ventricular
      ejection fraction (0.41 vs. 0.43). CONCLUSIONS: The organization of a regional
      infarction-network with logistic alliance of community hospitals with one
      experienced interventional centre ensures timely PCI for patients with STEMI
      according to present guidelines even in rural areas.

PMID- 15457396
TI  - [Endomyocardial biopsy-guided diagnosis and treatment of inflammatory
      cardiomyopathies].
AB  - BACKGROUND: Over 50 % of cases of inflammatory cardiomyopathy are caused by
      bacterial or viral infection, the latter frequently Parvovirus B19, enterovirus
      (Coxsackie B virus) or adenovirus. Regarding the pathogenesis of the disease, its
      early phase is dominated by the infectious pathogen, which directly damages the
      myocardium, while in the second phase an important role is played by activation
      of the immune system and the antiviral immune response with immunological
      processes. HISTORY AND CLINICAL FINDINGS: A 24-year-old woman (height 175 cm,
      weight 88 kg) was admitted because of recurrent exertional dyspnea. She also
      reported increased feeling of weakness, fainting and vertigo for the preceding
      six months. She reported an influenza-like infection just before the onset of
      these symptoms. EXAMINATIONS: No abnormalities were found on physical
      examination. But echocardiography revealed markedly reduced ventricular
      contractility with an ejection fraction (EF) of 30 %. A cardiac catheterization
      was performed, as part of which a myocardial biopsy was obtained. DIAGNOSIS,
      TREATMENT AND COURSE: The biopsies showed an inflammatory cardiomyopathy and
      Parvovirus B19 was demonstrated. The patient received the accepted management of
      heart failure plus hyper-immunoglobins, 2 x 10 g i. v. on days 1 and 3. This
      treatment resulted in marked and lasting improvement of the clinical symptoms.
      After 36 months the clinical status was only slightly reduced, the EF being 40 %
      and the LV end-diastolic dimension 56 mm. CONCLUSION: Without an endomyocardial
      biopsy it would have been impossible to establish the diagnosis of inflammatory
      cardiomyopathy due to Parvovirus B19. It was only through the demonstration of
      the causative pathogen in myocardium that it was possible to provide
      aetiologically targeted treatment.

PMID- 15457397
TI  - [Complicated course of Churg-Strauss syndrome with eosinophilic perimyocarditis
      and pericardial tamponade].
AB  - HISTORY: A 30-year-old patient suffered from a dry cough and increasing dyspnea
      since two years; he further complained about non radiating chest pain and weight
      loss of 15 kg in the past 8 weeks. EXAMINATIONS: Physical examination revealed
      pulsus paradoxus and distended neck veins. On chest x-ray, signs of cardiomegaly
      without infiltrations were found. Echocardiographic studies demonstrated a large
      pericardial effusion with signs of pericardial tamponade. Pericardiocentesis and
      pericardioscopy was performed and pericardial as well as epimyocardial biopsy
      samples were taken. Serum studies revealed increased markers of myocardial
      infarction and hypereosinophilia without clinical evidence of parasitic,
      myeloproliferative, or neoplastic diseases. Diagnosis of acute eosinophilic
      myocarditis was established in the epimyocardial biopsy samples. DIAGNOSIS,
      TREATMENT AND COURSE: Based on the clinicopathologic findings, we diagnosed Churg
      Strauss syndrome with cardiac involvement. We instilled 500 mg triamcinolone
      intrapericardially and initiated systemic treatment with corticosteroids which
      resulted in normalization of the blood eosinophil count. During a follow up of 18
      months, no recurrence of pericardial effusion was detected. However, while trying
      to reduce the steroids below 15 mg prednisolone equivalent per day, eosinophil
      numbers raised and wheezing increased. We suggested an immunosuppressive therapy
      including cyclophosphamide according to the Fauci protocol, which was denied by
      the patient due to potential adverse side effects. CONCLUSION: We suggest a
      detailed invasive strategy including endomyocardial biopsy to rule out viral
      myocarditis before immunosuppressive therapy with steroids is initiated in
      patients with suspected cardiac involvement in Churg Strauss syndrome.

PMID- 15457398
TI  - [Cardiomyopathies and magnetic resonance imaging].

PMID- 15457399
TI  - [Virus etiology of inflammatory cardiomyopathy].
AB  - Molecular biological methods such as in situ hybridization and the polymerase
      chain reaction (PCR) have confirmed the pathogenetic role of enteroviruses and
      primarily coxsackieviruses of group B (CVB) in the induction and maintenance of
      inflammatory cardiomyopathy. More recently, additional viruses such as
      adenoviruses (ADV), various herpes viruses and increasingly parvovirus B19
      (PVB19) have been identified as potential cardiotropic agents in the human heart.
      The different cell tropism of cardiotropic viruses implicates distinct
      pathogenetic principles. Whereas cardiac myocytes are target cells for infection
      with enteroviruses and adenoviruses with consecutive virus-induced cytolysis,
      PVB19-associated inflammatory cardiomyopathy is characterized by infection of
      intracardiac endothelial cells of small arterioles and veins, which may be
      associated with endothelial dysfunction, impairment of myocardial
      microcirculation, penetration of inflammatory cells and secondary myocyte
      necrosis.

PMID- 15457400
TI  - [Mechanisms of transplant vasculopathy].
AB  - Cardiac allograft vasculopathy is a diffuse, obliterative form of
      arteriosclerosis that is characterized by the production of a neointima rich in
      vascular smooth muscle cells that progressively obstructs the lumen.
      Pathophysiologically, after heart transplantation, alloantigens (e. g. on donor
      endothelial cells) are presented by antigen presenting cells to the T-cells of
      the body's immune system. With the appropriate costimulatory signal, this signal
      pattern generates a differentiated T-cell, B-cell, and inflammatory cell response
      whereas without the second signal, the immune cells undergo apoptosis. In case of
      immune cell proliferation and differentiation, a coordinated pattern of cytokine
      release is initiated. Cells of innate immunity, monocyte-derived macrophages, are
      involved in this process. The inflammatory response culminates in rolling,
      sticking, and diapedesis through the coronary vascular endothelium and migration
      and phenotype switch of medial smooth muscle cells mediated by generation of
      growth-promoting cytokines.

PMID- 15457401
TI  - [Gene and cell therapy for arrhythmia: realistic perspective or utopia?].

PMID- 15457402
TI  - [Peridural injections during acetylsalicylic acid and clopidogrel therapy?].

PMID- 15457403
TI  - Ethiopian mitochondrial DNA heritage: tracking gene flow across and around the
      gate of tears.
AB  - Approximately 10 miles separate the Horn of Africa from the Arabian Peninsula at
      Bab-el-Mandeb (the Gate of Tears). Both historic and archaeological evidence
      indicate tight cultural connections, over millennia, between these two regions.
      High-resolution phylogenetic analysis of 270 Ethiopian and 115 Yemeni
      mitochondrial DNAs was performed in a worldwide context, to explore gene flow
      across the Red and Arabian Seas. Nine distinct subclades, including three newly
      defined ones, were found to characterize entirely the variation of Ethiopian and
      Yemeni L3 lineages. Both Ethiopians and Yemenis contain an almost-equal
      proportion of Eurasian-specific M and N and African-specific lineages and
      therefore cluster together in a multidimensional scaling plot between Near
      Eastern and sub-Saharan African populations. Phylogeographic identification of
      potential founder haplotypes revealed that approximately one-half of haplogroup
      L0-L5 lineages in Yemenis have close or matching counterparts in southeastern
      Africans, compared with a minor share in Ethiopians. Newly defined clade L6, the
      most frequent haplogroup in Yemenis, showed no close matches among 3,000 African
      samples. These results highlight the complexity of Ethiopian and Yemeni genetic
      heritage and are consistent with the introduction of maternal lineages into the
      South Arabian gene pool from different source populations of East Africa. A high
      proportion of Ethiopian lineages, significantly more abundant in the northeast of
      that country, trace their western Eurasian origin in haplogroup N through
      assorted gene flow at different times and involving different source populations.

PMID- 15457405
TI  - Etruscan artifacts.

PMID- 15457404
TI  - Functional analysis of genetic variation in catechol-O-methyltransferase (COMT):
      effects on mRNA, protein, and enzyme activity in postmortem human brain.
AB  - Catechol-O-methyltransferase (COMT) is a key enzyme in the elimination of
      dopamine in the prefrontal cortex of the human brain. Genetic variation in the
      COMT gene (MIM 116790) has been associated with altered prefrontal cortex
      function and higher risk for schizophrenia, but the specific alleles and their
      functional implications have been controversial. We analyzed the effects of
      several single-nucleotide polymorphisms (SNPs) within COMT on mRNA expression
      levels (using reverse-transcriptase polymerase chain reaction analysis), protein
      levels (using Western blot analysis), and enzyme activity (using catechol
      methylation) in a large sample (n = 108) of postmortem human prefrontal cortex
      tissue, which predominantly expresses the -membrane-bound isoform. A common
      coding SNP, Val158Met (rs4680), significantly affected protein abundance and
      enzyme activity but not mRNA expression levels, suggesting that differences in
      protein integrity account for the difference in enzyme activity between alleles.
      A SNP in intron 1 (rs737865) and a SNP in the 3' flanking region (rs165599)--both
      of which have been reported to contribute to allelic expression differences and
      to be associated with schizophrenia as part of a haplotype with Val--had no
      effect on mRNA expression levels, protein immunoreactivity, or enzyme activity.
      In lymphocytes from 47 subjects, we confirmed a similar effect on enzyme activity
      in samples with the Val/Met genotype but no effect in samples with the intron 1
      or 3' SNPs. Separate analyses revealed that the subject's sex, as well as the
      presence of a SNP in the P2 promoter region (rs2097603), had small effects on
      COMT enzyme activity. Using site-directed mutagenesis of mouse COMT cDNA,
      followed by in vitro translation, we found that the conversion of Leu at the
      homologous position into Met or Val progressively and significantly diminished
      enzyme activity. Thus, although we cannot exclude a more complex genetic basis
      for functional effects of COMT, Val is a predominant factor that determines
      higher COMT activity in the prefrontal cortex, which presumably leads to lower
      synaptic dopamine levels and relatively deleterious prefrontal function.

PMID- 15457406
TI  - On the Etruscan mitochondrial DNA contribution to modern humans.

PMID- 15457408
TI  - GDD1 is identical to TMEM16E, a member of the TMEM16 family.

PMID- 15457411
TI  - A prospective, randomized, double-blind study of smooth versus rough stems using
      cement fixation: minimum 5-year follow-up.
AB  - This prospective randomized double-blind study aims to evaluate the effect of
      surface finish of the cemented femoral stem in primary total hip arthroplasty.
      Between January 1996 and May 1997, a single surgeon prospectively implanted 244
      primary THAs (237 patients) using cemented femoral stems with modified third
      generation cement technique in selected patients. Patients were randomized to
      receive the Ranawat-Burstein prosthesis (Biomet, Warsaw, IN) with 1 of 2 finishes
      (smooth-Ra 17 or rough-Ra 170). At a minimum 5-year follow-up, no statistical
      differences were found between the 2 groups. One patient with a smooth stem
      underwent revision of the femoral component at 2 years secondary to aseptic
      loosening. There was no other evidence of radiographic loosening or osteolysis.
      As an isolated variable, surface finish does not appear to significantly
      influence results at mean follow-up of 6.5 years.

PMID- 15457412
TI  - Thigh pain in primary total hip arthroplasty: the effects of elastic moduli.
AB  - Thigh pain after uncemented total hip arthroplasty (THA) remains a controversial
      topic. Our objective was to assess the effect of material composition in the
      development of thigh pain after primary THA. A cohort of 241 primary THAs was
      followed for a minimum of 2 years. All patients received identically shaped
      tapered cementless femoral components; the first half received a Cr-Co-Mo implant
      and the other half an identical implant made of Ti-6Al-4V. There were no
      statistically significant preoperative differences in the 2 component groups
      except that the percentage of blacks in the Cr-Co-Mo group was larger than in the
      Ti-6Al-4V group (26% vs. 14%; P <.05). The overall 1- and 2-year incidence of
      thigh pain was 9.5% and 8.7%, respectively. Implant composition was unrelated to
      reported thigh pain 1 and 2 years postoperatively. However, patients receiving
      larger versus smaller stems irrespective of material composition were more likely
      to report thigh pain at year 1 (relative risk = 4.68; 95% confidence interval =
      1.41, 15.50). Thigh pain reported at year 2 was also higher in patients with
      larger versus smaller implants; however, this difference was not statistically
      significant (RR = 1.73; 95% CI = 0.68, 4.43). Material composition of this
      tapered stem design is unrelated to the incidence of thigh pain.

PMID- 15457413
TI  - Cerclage wires or cables for the management of intraoperative fracture associated
      with a cementless, tapered femoral prosthesis: results at 2 to 16 years.
AB  - Initial stability is critical for fixation and survival of cementless total hip
      arthroplasty. Occasionally, a split of the calcar occurs intraoperatively. A
      review of 1,320 primary total hip arthroplasties with 2-year follow-up, performed
      between August 1985 and February 2001 using the Mallory-Head Porous tapered
      femoral component, revealed 58 hips in 55 patients with an intraoperative calcar
      fracture managed with single or multiple cerclage wires or cables and immediate
      full weight bearing. At 7.5 years average follow-up (range, 2-16 years), there
      were no revisions of the femoral component, radiographic failures, or patients
      with severe thigh pain, for a stem survival rate of 100%. Average Harris hip
      score improvement was 33.8 points. Fracture of the proximal femur occurs in
      approximately 4% of primary THAs using the Mallory-Head Porous femoral component.
      When managed intraoperatively with cerclage wire or cable, the mid- to long-term
      results appear unaffected with 100% femoral component survival at up to 16 years.

PMID- 15457414
TI  - Assessing the pattern of femoral head penetration after total hip arthroplasty.
AB  - We evaluated temporal changes in wear rates among 205 primary cementless total
      hip arthroplasties that had minimum 10-year follow-up and at least 6 follow-up x
      rays. Using the pelvic anteroposterior x-rays from each hip, two-dimensional head
      penetration was measured and wear rates were calculated using several techniques.
      The average wear rate for the study population did not demonstrate evidence of
      accelerated wear at 10- to 18-year follow-up. As an increasing number of follow
      up x-rays were included in the least-squares linear regression used to calculate
      the wear rate, the 95% confidence interval associated with the wear rate for an
      individual hip tended to progressively decrease. These results indicate that a
      constant wear rate is a reasonable assumption for modeling clinical wear data.
      Although we cannot quantify the effects of polyethylene oxidation, femoral head
      roughening, debris accumulation, or activity level changes, the combination of
      these factors is not leading to clinically perceptible accelerated wear at
      intermediate to long-term follow-up in this heterogeneous population of cups
      representing our institutional experience.

PMID- 15457415
TI  - Examination of surface and material properties of explanted zirconia femoral
      heads.
AB  - The crystalline structure of Zirconia femoral heads provides for superior
      fracture toughness when compared with alumina. Transformation of the crystalline
      structure that takes place with time in service may produce changes in the
      surface and biomechanical properties of these implants. This study examines
      surface and mechanical property changes of Zirconia femoral heads that occur with
      time in situ. Eighteen retrieved Zirconia femoral heads were compared to 5
      factory-sealed controls. The retrieved implants demonstrated significant
      transformation to a monoclinic phase. This phase transformation was associated
      with decreased surface hardness. There was evidence of increased surface
      roughness with increasing time of implantation. The phase transformation that
      takes place in Zirconia femoral heads may render these implants less desirable as
      a bearing surface in total hip arthroplasty.

PMID- 15457416
TI  - Metal-on-metal versus metal-on-polyethylene bearings in total hip arthroplasty: a
      matched case-control study.
AB  - This case-control study was performed to investigate the hypothesis that metal-on
      metal (M-M) bearings reduce the risk of aseptic component loosening when compared
      with metal-on-polyethylene (M-PE) bearings. Cases were identified from a
      computerized joint database as patients who had received a primary total hip
      arthroplasty using an M-M or M-PE bearing and had documented revision or
      radiographic loosening of the stem or cup. Multiple controls were matched to each
      case for gender, age, diagnosis, hospital, operation date, follow-up, stem type,
      and cup design. Odds ratios were determined to identify the risk of component
      loosening for either bearing surface. In all, 505 cases and 1,605 controls were
      identified. M-M bearings demonstrated a lower risk of aseptic stem and/or cup
      loosening than M-PE bearings; however, this was not statistically significant.

PMID- 15457417
TI  - Mid-term results of a polyethylene-free metal-on-metal articulation.
AB  - Beginning in December 1995, 193 patients (195 hips) were enrolled into this
      prospective, randomized, controlled multicenter investigational device exemption
      study. Ninety-eight patients (99 hips) with 46 polyethylene liners and 53 metal
      liners had minimum 5-year follow-up (mean, 5.7 years). Average follow-up, Harris
      hip score improvement, and radiographic analysis were not statistically different
      between groups. No stress shielding or osteolysis was observed in either group.
      Three polyethylene liners and no metal liners had acetabular radiolucencies <1 mm
      in 1 or more zones. There have been no device-related complications, no
      acetabular revisions performed, and none pending in either group. Based on these
      mid-term results, the authors conclude that a metal-on-metal articulation
      represents a viable alternative in young, high-demand, active patients.

PMID- 15457418
TI  - Three- to six-year results with the Ultima metal-on-metal hip articulation for
      primary total hip arthroplasty.
AB  - One hundred seventy-one primary total hip arthroplasties were evaluated in a
      prospective, randomized study. Ninety-five involved a metal-backed cup with an
      all-metal liner and 76 involved a metal-backed polyethylene cup that was used as
      the control. All were implanted with an S-ROM cementless femoral component with a
      28 mm head. The mean follow-up period was 3.7 years (range, 3.0-5.7). The average
      postoperative Harris hip score was 95.4 (range, 65-100) for the metal-on-metal
      group and 96.1 (range, 65-100) for the metal-on-polyethylene group. Radiographic
      results were not statistically different between the 2 groups. Early results show
      the metal-on-metal articulation has been successful to date and justify continued
      clinical use.

PMID- 15457419
TI  - Long-term porous-coated cup survivorship using spikes, screws, and press-fitting
      for initial fixation.
AB  - This study examined the long-term outcome of a single institution's experience
      with 4,289 primary total hip arthroplasties using hemispheric porous-coated cups.
      Initial fixation was achieved with spikes (255 AML TriSpike cups), by press
      fitting with rim screws (427 Arthropor cups) or by press-fitting the component
      (83 Harris-Galante, 391 ACS Triloc+, 2,537 Duraloc, and 596 Pinnacle cups). Among
      203 revised hips, only 18 cups were found to be loose at the time of revision.
      Using revision for any reason as an end point, 15-year survivorship was 82.9% +/-
      5.6% (95% confidence interval) for spiked components, 71.6% +/- 8.5% for press
      fit cups with adjunctive rim screws, and 72.0% +/- 12.6% for press-fit components
      (P<.001, log rank). Using revision for aseptic loosening as an end point, 15-year
      survivorship was 94.7% +/- 3.4% for spiked cups, 98.4% +/- 1.9% for press-fit
      cups with screws and 100% +/- 0.1% for press-fit cups. Despite an increasing
      incidence of polyethylene wear-related revisions, porous-coated acetabular
      components have demonstrated excellent long-term fixation.

PMID- 15457420
TI  - Early morbidity of modular exchange for polyethylene wear and osteolysis.
AB  - This study assessed the early morbidity associated with modular component
      exchange surgery for the treatment of accelerated polyethylene wear and
      osteolysis in 55 patients. Review of the surgical records revealed no significant
      intraoperative complications, little intraoperative blood loss (mean 333 mL), no
      allogenic blood transfusions, and no recorded postoperative deep vein thromboses.
      Eighteen percent of patients, however, experienced postoperative dislocation.
      Five patients dislocated multiple times, 3 of which required rerevision surgery.
      Two patients required rerevision for femoral implant fractures related to
      osteolysis and 1 additional patient required rerevision due to catastrophic
      failure of the acetabular component 5 years postoperatively. With an average
      follow-up of 30 months, 6 of the 55 patients treated with modular exchange
      required rerevision. The results of this study suggest that instability is the
      most prevalent early complication associated with modular component exchange. As
      such, we believe that more stable constructs should be emphasized, possibly at
      the expense of polyethylene thickness.

PMID- 15457421
TI  - Acetabular revision with a modular anti-protrusio acetabular component.
AB  - Current anti-protrusio cages are non-porous-coated and 1 piece and they require
      liner cementation. These factors limit bone ingrowth, trials, and modularity.
      Results of a completely modular porous-coated anti-protrusio component (MAPC) are
      presented. Sixty-three acetabular revisions with MAPC were performed from 1998
      2001 by 2 surgeons. Average follow-up was 29 months (range, 24-50). 30/63 (48%)
      had Paprosky type 3A or B defects. 55/63 (87%) MAPCs remain in place. Four
      components were removed for infection, 3 for loosening, and 1 for malposition.
      Eight hips dislocated, requiring 6 reoperations. Two MAPCs are radiographically
      loose but asymptomatic. At short-term follow-up, these results are comparable to
      conventional 1-piece anti-protrusio cages. Advantages include the potential for
      bone ingrowth and long-term fixation, surgical technique similar to large
      hemispherical components, ability to trial, and modularity.

PMID- 15457422
TI  - Cementless bipolar hemiarthroplasty for displaced femoral neck fractures in the
      elderly.
AB  - Controversy exists regarding the use of cementless femoral fixation for hip
      arthroplasties in elderly patients. This study reviews the clinical and
      radiographic outcomes of cementless bipolar hemiarthroplasties in patients older
      than 65 years of age. From 1998 to 2000, 256 cementless bipolar
      hemiarthroplasties were performed in 248 patients with displaced femoral neck
      fractures who had a mean age of 77 years. The mean final follow-up was 3.5 years
      and Harris hip scores averaged 82 points. Two loose femoral stems were revised
      and the rest of the implants were radiographically stable and demonstrated
      evidence of bone ingrowth. Six patients had debilitating groin pain necessitating
      conversion to total hip arthroplasty. Cementless bipolar hemiarthroplasty can be
      safely performed in elderly patients and can provide predictable clinical and
      radiographic results.

PMID- 15457423
TI  - Efficacy of fondaparinux for thromboprophylaxis in hip fracture patients.
AB  - Fondaparinux efficacy for thromboprophylaxis was evaluated in predefined high
      risk hip fracture patients. Patients received fondaparinux 2.5 mg for 7 days
      following surgery; 656 patients were randomized double blind to receive placebo
      or continue fondaparinux regimen for 21 additional days. Primary efficacy was
      venous thromboembolism (VTE) based on bilateral venography during the double
      blind period. Total VTE was 1.4% (3 of 208 patients) for extended prophylaxis and
      35% (77 of 220 patients) for short-term prophylaxis (P = 0.001), relative risk
      reduction (RRR) of 96%. Major bleeding occurred in 2% (8 of 327 patients) with
      extended prophylaxis and in 0.6% (2 of 329 patients) with short-term prophylaxis
      (P =.063). Risk of VTE was continued following short course fondaparinux in hip
      fracture patients, but was significantly reduced by extending prophylaxis,
      without significant risk of major bleeding.

PMID- 15457424
TI  - Ileus following total hip or knee arthroplasty is associated with increased risk
      of deep venous thrombosis and pulmonary embolism.
AB  - Venous thromboembolic disease (VTD), deep venous thrombosis and pulmonary
      embolism, causes morbidity and mortality following total hip and total knee
      arthroplasties, while ileus complicates up to 4.0%. The clinical courses of 2,949
      patients undergoing 3,364 consecutive primary and revision total hip and total
      knee arthroplasties, radical debridements, and reimplantations at one institution
      over a 2-year period were reviewed to examine the relationship between ileus and
      VTD. VTD prophylaxis consisted of aspirin and intermittent plantar pulse boots
      for all patients except those at high risk, who received parenteral chemical
      prophylaxis and boots. Ileus occurred in 62 patients (2.1%) and symptomatic DVT
      in 51 (1.7%). With ileus, the incidence of DVT was 8.1%: odds ratio 5.5 (P
      =.0036). Symptomatic pulmonary embolism occurred in 7 patients (0.24%); with
      ileus the incidence was 3.2%: odds ratio 19.6 (P =.0082). A significant increase
      was observed in rates of VTD with ileus. We recommend using parenteral chemical
      and mechanical prophylaxis in patients with ileus following total hip and total
      knee arthroplasties.

PMID- 15457425
TI  - Mobile-bearing unicompartmental knee arthroplasty: a 2-center study with an 11
      year (mean) follow-up.
AB  - The original Oxford and Low Contact Stress mobile-bearing unicompartmental knee
      designs have been used successfully since the mid-1970s, but have had limited
      exposure. Our study reviews 177 LCS unicompartment replacements (156 medial) with
      5-19 years follow-up. Mean age was 68 years, 70% were female, with osteoarthritis
      (OA) diagnosis in 96%. Fixation was cementless in 72% and cemented in 28%.
      Results were good/excellent [modified Hospital for Special Surgery (HSS)] in 82%.
      Scores improved from 60 to 86, mean range of motion 123 degrees. Complications
      requiring reoperation were 32 of 177 knees (18%). Early failures were technique
      related and late failures (3+ years) related to bearing wear/fracture; 15 cases
      required bearing exchange alone. Low contact stress mobile-bearing
      unicompartmental knee arthroplasties with 82% prosthetic survivorship at 11 years
      is encouraging, especially in a more active population and with the success of
      bearing exchange.

PMID- 15457426
TI  - Hybrid total knee arthroplasty: a retrospective analysis of clinical and
      radiographic outcomes at average 10 years follow-up.
AB  - Cemented total knee arthroplasty has demonstrated high success rates at 10-12
      years. Although many cementless designs have demonstrated inferior outcomes,
      hybrid fixation has not been studied in detail. We retrospectively reviewed 112
      hybrid total knee arthroplasties (PCA-67 and Duracon-45) after clinical and
      radiographic review using the SF-12 and Knee Society Scores at an average 10-year
      follow-up. The revision rate was 4.5%: 4 occurred in patients with metal-backed
      patellae and 1 in a patient with infection. No revisions were performed for
      aseptic loosening of the femoral component. Hybrid total knee arthroplasty with
      these designs provided excellent clinical and radiographic performance at 10
      years comparable to cemented series. Aseptic loosening and radiographic failure
      rates were 0% if patients with metal-backed patellae were excluded. The
      durability of hybrid fixation beyond 10 years deserves further study.

PMID- 15457427
TI  - Winner of the 2003 James A. Rand Young Investigator's Award. Early failure of
      cementless mobile-bearing total knee arthroplasty.
AB  - A consecutive series of 82 cementless mobile-bearing total knee arthroplasties
      performed was studied to determine the reliability of cementless tibial component
      fixation. The indications for surgery in all cases were osteoarthritis with only
      mild or moderate deformity. Evaluation consisted of a Knee Society clinical score
      (KSCS) and radiographic evaluation preoperatively and at annual follow-up.
      Minimum 2-year follow-up was obtained in 73 of 82 knees (89%). Results were
      compared to those of a subsequent consecutive series of 76 knees (66 with 2-year
      follow-up) performed with a mobile-bearing TKA with cemented components with the
      same indications, implant, technique, and length of follow-up. Six of 73
      cementless mobile-bearing TKAs (8%) underwent tibial component revision for
      symptomatic subsidence and failure of ingrowth compared to 0/66 revisions in the
      cemented group (P<.05). Patients with cementless mobile-bearing TKA also had a
      significantly lower KSCS (161 versus 184, P<.05), significantly higher incidence
      of pain rated more than mild (23% versus 7%, P<.01) and a trend toward less arc
      of motion (106 degrees versus 115 degrees, P<.2). The results do not support the
      hypothesis that mobile-bearing TKA imparts the advantage of reliable tibial bone
      ingrowth.

PMID- 15457428
TI  - The PCL significantly affects the functional outcome of total knee arthroplasty.
AB  - This study tests the hypothesis that patients receiving a posterior cruciate
      ligament (PCL)-retaining prosthesis have no difference in functional outcome
      compared to those receiving a cruciate-sacrificing, posterior-stabilized (PS)
      design. Forty-nine patients underwent a total knee arthroplasty (TKA), performed
      by a single surgeon using the same implant design with either a PCL-retaining or
      a PS tibial insert. Each patient completed a self-administered, validated Total
      Knee Function Questionnaire as well as the SF-36. At 1-year follow-up, each
      patient's range of motion and Knee Society knee score were measured. There were
      no statistically significant differences between the 2 groups using the
      traditional measures of function following total knee replacement, including
      overall satisfaction with surgery. However, the TKFQ revealed that patients with
      PS knees reported greater functional limitations in squatting, kneeling, and
      gardening. Our results suggest that with the specific implant used in this study,
      substitution for the PCL with a spine and cam mechanism may not fully restore the
      functional capacity of the intact PCL, particularly in high-demand activities
      that involve deep flexion.

PMID- 15457429
TI  - The optimal strategy for stable tibial fixation in revision total knee
      arthroplasty.
AB  - In revision total knee arthroplasty, the optimal strategy for stabilizing the
      tibial component in the face of proximal defects remains controversial. The
      stability of a revision tibial prosthesis was measured using a mechanical
      surrogate of the revision tibia, while varying the defect treatment proximally
      and the cortical engagement distally. An offset axial load in combination with an
      axial torque were applied to each specimen to simulate the stance phase of gait.
      It was found that, in revision total knee arthroplasty, the mechanical stability
      of tibial fixation is increased by the addition of a canal filling stem,
      especially in the presence of poor proximal bone. Proximal tibial coverage, even
      with a custom-fitted tibial component, adds little additional stability to a
      tibial tray stabilized by intramedullary engagement of a canal-filling stem.

PMID- 15457430
TI  - The effect of stem design on end-of-stem pain in revision total knee
      arthroplasty.
AB  - A series of 143 revision total knee arthroplasties was evaluated using a Knee
      Society clinical score, radiographic assessment, and satisfaction questionnaire.
      Patients completed a pain drawing showing the location and severity of pain they
      experienced at 2 years follow-up. Two stem designs were used: a solid, fluted
      cobalt chrome stem (group I) and a slotted titanium stem (group II). End-of-stem
      pain was associated with solid cobalt chrome stems while a lower incidence of
      stem pain was associated with slotted titanium stems. Symptoms were intermittent
      and activity related in all but 2 cases, but none required component revision.
      The presence of end-of-stem pain did appear to be clinically significant because
      patients with this pain were more likely to be only somewhat satisfied or
      dissatisfied with their degree of pain relief compared to those without end-of
      stem pain. Stem design does appear to impact the incidence of end-of-stem pain in
      revision total knee arthroplasty.

PMID- 15457431
TI  - Psychological attributes of preoperative total joint replacement patients:
      implications for optimal physical outcome.
AB  - In this study, 107 primary total joint replacement (TJR) patients were assessed
      preoperatively using the SF-36 (Mental Component Score [MCS] and Physical
      Component Score [PCS]), Beck Depression Inventory (BDI), Spielberger Trait
      Anxiety Inventory, Interpersonal Support Evaluation List, and the Coping
      Strategies Questionnaire. Patients with preoperative MCS < 50 had significantly
      higher trait anxiety (P <.001), higher BDI scores (P <.001), and lower appraisal
      (P <.018) and belonging (P <.006) support when compared with patients with
      preoperative MCS > or = 50. Low MCS patients used more catastrophizing coping
      techniques (P <.001) and reported poorer pain control (P <.04). A multivariate
      prediction model found that adding preoperative MCS to baseline demographic and
      physical function (PCS) measures significantly improved the prediction of 6-month
      change in PCS. Further research should evaluate the role of multimodality
      emotional support in assuring optimal physical return after TJR.

PMID- 15457432
TI  - Inflammatory bowel diseases as an intermediate stage between normal and cancer: a
      FTIR-microspectroscopy approach.
AB  - Elucidation of the evolution of inflammatory bowel disease (IBD) to cancer by
      clinical symptoms and histopathology of biopsies is important. Fourier transform
      infrared microspectroscopy (FTIR-MSP) has shown promise as a diagnostic tool for
      distinction of normal and cancer cells and tissues. In the present work, FTIR-MSP
      is used to evaluate IBD cases and to study the IR spectral characteristic with
      respect to cancer and normal tissues from formalin-fixed colonic biopsies from
      patients. Specific regions of the spectra were analyzed by statistical tools to
      study variations in metabolites that signified changes between the two
      pathological conditions: IBD and cancer. IBD tissues can be grouped with cancer
      or normal tissue using certain parameters such as phosphate content and RNA/DNA
      ratio as calculated from the spectra and show intermediate levels with regard to
      these metabolites. Further classification of the spectra by cluster analysis
      indicated which cases of Crohn's disease (3 of 10 cases) or ulcerative colitis (7
      of 10 cases) were more likely to progress to cancer. The study exhibits that FTIR
      MSP can detect gross biochemical changes in morphologically identical IBD and
      cancer tissues and suggest which cases of IBD may require further evaluation for
      carcinogenesis.

PMID- 15457434
TI  - NMR solution structure of a highly stable de novo heterodimeric coiled-coil.
AB  - The NMR solution structure of a highly stable coiled-coil IAAL-E3/K3 has been
      solved. The E3/K3 coiled-coil is a 42-residue de novo designed coiled-coil
      comprising three heptad repeats per subunit, stabilized by hydrophobic contacts
      within the core and electrostatic interactions at the interface crossing the
      hydrophobic core which direct heterodimer formation. This E3/K3 domain has
      previously been shown to have high alpha-helical content as well as possessing a
      low dissociation constant (70 nM). The E3/K3 structure is completely alpha
      helical and is an archetypical coiled-coil in solution, as determined using a
      combination of (1)H-NOE and homology based structural restraints. This structure
      provides a structural framework for visualizing the important interactions for
      stability and specificity, which are key to protein engineering applications such
      as affinity purification and de novo design.

PMID- 15457435
TI  - Removal of the side-chain glucose groups from schizophyllan improves the thermal
      stability of the polycytidylic acid complexes under the physiological conditions.
AB  - Thermal stabilization of the complex between polycytidylic acid [poly(C)] and the
      modified schizophyllan (SPG) whose hydrophilic side-chain glucose groups are
      selectively removed utilizing mild Smith-degradation has been investigated. With
      the decrease in the side-chain glucose groups of schizophyllan, the complex with
      poly(C) can be considerably stabilized compared with unmodified SPG; for example,
      the T(m) value after the removal of the side-chain glucose groups from 33.3
      (unmodified) to 1.0 is enhanced by 14 degrees C. In addition, the thermal
      stabilization effect is even operative under the physiological conditions ([NaCl]
      = 0.15 mol dm(-3)). This effect is exerted owing to the construction of the
      hydrophobic atmosphere around the complex. Although schizophyllan lost the side
      chain glucose groups, it still kept the protection effect of the bound poly(C)
      chain against RNaseA-mediated hydrolysis as observed for unmodified
      schizophyllan. The assessment of the cytotoxicity for A375:human malignant
      melanoma, and HL60:human promyelocytic leukemia revealed that the modified
      schizophyllan scarcely increases the cytotoxicity. These results indicate that
      the present modification for schizophyllan is of great significance in a
      viewpoint to develop the practical gene carriers operative even under the
      physiological conditions.

PMID- 15457436
TI  - Gelation of gellan gum aqueous solutions studied by polarization modulation
      spectroscopy.
AB  - Circular birefringence (CB, or optical rotation) and linear birefringence (LB)
      were measured for gellan gum aqueous solutions with and without salt to examine
      the gelling system in the helical structure as well as in the orientation. It was
      found that gelling samples with salt show nonzero LB values, whereas LB is zero
      for the samples without salt even in the gel state. This difference can be
      explained by the thermal deformation of the system containing anisotropic
      aggregations of helices formed with the shielding effect of the added salt on the
      intramolecular and intermolecular electrostatic repulsions. Considering that the
      presence of LB in the system affects the estimation of CB, we developed an
      original procedure of the CB measurement to eliminate the contribution of LB. It
      was shown that our methods for eliminating the contribution of LB can improve the
      CB measurement for the gellan gum gel. The temperature dependence of [alpha] for
      the samples with salt in the gel state is quite different from that for the
      samples without salt, suggesting that the aggregates of helices in the samples
      containing a high concentration of salt form a supramolecular structure that
      contributes to CB.

PMID- 15457437
TI  - Pressure dependence of human fibrinogen correlated to the conformational alpha
      helix to beta-sheet transition: an Fourier transform infrared study
      microspectroscopic study.
AB  - We used Fourier transform infrared (FTIR) microspectroscopy to investigate
      pressure-induced conformational changes in secondary structure of fibrinogen
      (FBG). Solid state FBG was compressed on a KBr pellet (1KBr method) or between
      two KBr pellets (2KBr method). The peak positions of the original and second
      derivative ir spectra of compressed FBG samples prepared by the 1KBr method were
      similar to FBG sample without pressure. When FBG was prepared by the 2KBr method
      and pressure was increased up to 400 kg/cm(2), peaks at 1625 (intermolecular beta
      sheet) and 1611 (beta-sheet aggregates structure and/or the side-chain absorption
      of the tyrosine residues) cm(-1) were enhanced. The peaks near 1661 (beta-sheet)
      and 1652 (alpha-helix) cm(-1) also exhibited a marked change with pressure. A
      linear correlation was found between the peak intensity ratio of 1611/1652 cm(-1)
      (r = 0.9879) or 1625/1652 cm(-1) (r = 0.9752) and applied pressure. The curve
      fitted compositional changes in secondary structure of FBG also indicate that the
      composition of the alpha-helix structure (1657-1659 cm(-1)) was gradually reduced
      with the increase in compression pressure, but the composition of the beta-sheet
      structure (1681, 1629, and 1609 cm(-1)) gradually increased. This indicates that
      pressure-induced conformational changes in FBG include not only transformations
      from alpha-helix to beta-sheet structure, but also unfolding and denaturation of
      FBG and the formation of aggregates.

PMID- 15457438
TI  - Regulatory/suppressor T cells in health and disease.

PMID- 15457439
TI  - Balanced treatments for fibromyalgia.

PMID- 15457440
TI  - B lymphocyte signaling pathways in systemic autoimmunity: implications for
      pathogenesis and treatment.

PMID- 15457441
TI  - Joint hypermobility syndromes: the pathophysiologic role of tenascin-X gene
      defects.

PMID- 15457442
TI  - The influence of genetic variation in the HLA-DRB1 and LTA-TNF regions on the
      response to treatment of early rheumatoid arthritis with methotrexate or
      etanercept.
AB  - OBJECTIVE: To examine the roles of specific genetic polymorphisms as predictors
      of response to treatment of early rheumatoid arthritis (RA). METHODS: Subjects
      included 457 patients with early RA (duration of < or =3 years) who participated
      in a randomized controlled trial comparing weekly methotrexate and 2 dosages of
      etanercept (10 mg twice weekly and 25 mg twice weekly). Our primary outcome
      measure was achievement of 50% improvement in disease activity according to the
      criteria of the American College of Rheumatology (ACR50 response) after 12 months
      of treatment. Subjects were genotyped for HLA-DRB1 alleles and polymorphisms in
      the following genes: TNF, LTA, TNFRSF1A, TNFRSF1B, FCGR2A, FCGR3A, and FCGR3B.
      Univariate and multivariate analyses were performed to define the impact of
      specific polymorphisms and haplotypes on response to treatment. Covariates for
      the multivariate analyses included sex, ethnicity, age, disease duration, and
      baseline values for rheumatoid factor and the tender and swollen joint counts.
      RESULTS: The presence of 2 HLA-DRB1 alleles encoding the shared epitope (SE)
      (compared with 1 or 0 copies) was associated with response to treatment with
      standard-dose etanercept (odds ratio [OR] 4.3, 95% confidence interval [95% CI]
      1.8-10.3). Among Caucasian patients, 2 extended haplotypes that included the HLA
      DRB1 alleles *0404 and *0101 (both of which encode the SE) and 6 single
      nucleotide polymorphisms in the LTA-TNF region were associated with response to
      treatment. In a multivariate model that included treatment received and the
      aforementioned covariates, the ORs for the association of these haplotypes with
      achievement of an ACR50 response at 12 months were 2.5 (95% CI 0.8-7.3) and 4.9
      (95% CI 1.5-16.1) for the *0404- and *0101-containing haplotypes, respectively.
      CONCLUSION: Genetic variation in the HLA-DRB1 and the LTA-TNF regions is
      significantly associated with response to treatment of early RA. These findings
      may have clinical application through the identification of patients who are most
      likely to benefit from treatment with methotrexate or etanercept.

PMID- 15457443
TI  - Dense genome-wide linkage analysis of rheumatoid arthritis, including covariates.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) is a heterogeneous disease that exhibits a
      complex genetic component. Previous RA genome scans confirmed the involvement of
      the HLA region and generated data on suggestive signals at non-HLA regions,
      albeit with few overlaps in findings between studies. The present study was
      undertaken to detect potential RA gene regions and to estimate the number of true
      RA gene regions, taking into account the heterogeneity of RA, through performance
      of a dense genome scan. METHODS: In a study of 88 French Caucasian families (105
      RA sibpairs), 1,088 microsatellite markers were genotyped (3.3-cM genome scan),
      and a multipoint model-free linkage analysis was performed. The statistical
      assessment of the results relied on 10,000 computer simulations. A covariate
      based multipoint model-free linkage analysis was performed on the locations of
      regions with suggestive evidence for linkage. RESULTS: Involvement of the HLA
      region was strongly confirmed (P = 6 x 10(-5)), and 19 non-HLA regions showed
      suggestive evidence for linkage (P < 0.05); 9 of these overlapped with regions
      suggested in other published RA genome scans. A routine 12-cM genome scan with
      the same families would have detected only 7 of the 19 regions, including only 4
      of the 9 overlapping regions. From the 10,000 computer simulations, we estimated
      that 8 +/- 4 regions (mean +/- SD) were true-positives. RA covariate-based
      analysis provided additional linkage evidence for 3 regions, with age at disease
      onset, erosions, and HLA-DRB1 shared epitope as covariates. CONCLUSION: The
      results of this study provide evidence of 19 non-HLA RA gene regions, with an
      estimate of 8 +/- 4 as true-positives, and provide additional evidence for 3
      regions from covariate-based analysis.

PMID- 15457444
TI  - Polyglutamation of methotrexate with common polymorphisms in reduced folate
      carrier, aminoimidazole carboxamide ribonucleotide transformylase, and
      thymidylate synthase are associated with methotrexate effects in rheumatoid
      arthritis.
AB  - OBJECTIVE: Methotrexate (MTX) enters cells through the reduced folate carrier
      (RFC-1) and exerts part of its effects through polyglutamation to MTX
      polyglutamates (MTXPGs) and inhibition of 5-aminoimidazole-4-carboxamide
      ribonucleotide transformylase (ATIC) and thymidylate synthase (TS). We
      investigated the contribution of common genetic polymorphisms in RFC-1 (G80A),
      ATIC (C347G), and TS (28-bp tandem repeats located in the TS enhancer region
      [TSER*2/*3]) and of MTXPGs to the effect of MTX in patients with rheumatoid
      arthritis. METHODS: The study was cross-sectional. All patients received MTX for
      at least 3 months. The numbers of tender and swollen joints, the Visual Analog
      Scale (VAS) scores for the physician's global assessment of disease activity, and
      the modified Health Assessment Questionnaire scores were collected. Using the VAS
      score for the physician's assessment of patient's response to MTX, the population
      of patients was dichotomized into responders to MTX (VAS score < or =2 cm) and
      nonresponders to MTX (VAS score >2 cm). A pharmacogenetic index was calculated as
      the sum of homozygous variant genotypes (RFC-1 AA + ATIC 347GG + TSER *2/*2)
      carried by the patients. MTXPG concentrations were measured in red blood cells
      (RBCs) by high-performance liquid chromatography. RESULTS: The dose of MTX was
      not associated with the effects of MTX (P > 0.05). In contrast, increased RBC
      long-chain MTXPG concentrations (median 40 nmoles/liter; range <5-131
      nmoles/liter) and an increased pharmacogenetic index were associated with a lower
      number of tender and swollen joints (P < 0.05) and a lower score for the
      physician's global assessment of disease activity (P < or = 0.001). Patients with
      RBC MTXPG levels of >60 nmoles/liter and carriers of a homozygous variant
      genotype were 14.0-fold (95% confidence interval [95% CI] 3.6-53.8) and 3.7-fold
      (95% CI 1.7-9.1), respectively, more likely to have a good response to MTX (P <or
      = 0.01). CONCLUSION: These data suggest that measuring RBC MTXPG levels and/or
      the common polymorphisms in the folate-purine-pyrimidine pathway may help in
      monitoring MTX therapy.

PMID- 15457445
TI  - CD4(+)CD25(+) regulatory T cells in rheumatoid arthritis: differences in the
      presence, phenotype, and function between peripheral blood and synovial fluid.
AB  - OBJECTIVE: In mice, CD4(+)CD25(+) regulatory T cells play a pivotal role in
      preventing autoimmunity. Regulatory T cells are also present and functional in
      healthy humans. We investigated the presence, phenotype, and function of
      CD4(+)CD25(+) regulatory T cells in peripheral blood (PB) and synovial fluid (SF)
      from patients with rheumatoid arthritis (RA). METHODS: The presence and phenotype
      of CD4(+)CD25(+) regulatory T cells were determined by flow cytometry. Anergy and
      suppressive activity were assessed by culturing CD4(+)CD25(-) and CD4(+)CD25(+) T
      cells with anti-CD3 monoclonal antibodies and antigen-presenting cells, followed
      by proliferation and cytokine detection. RESULTS: The percentage of CD4(+)CD25(+)
      T cells in RA SF was significantly increased compared with that in RA PB, and
      both of these percentages were higher than that in PB from controls. The cells in
      RA PB were similar in phenotype and function to CD4(+)CD25(+) regulatory T cells
      from controls. In SF, however, approximately 40-50% of CD4(+)CD25(+) T cells
      expressed an activated phenotype, i.e., CD69+, class II MHC(+), OX-40(+), with
      high levels of CTLA-4 and glucocorticoid-induced tumor necrosis factor receptor.
      These synovial CD4(+)CD25(+) T cells displayed an increased suppressive capacity
      compared with blood CD4(+)CD25(+) T cells. However, this enhanced suppressive
      activity was counterbalanced, because activated responder T cells from SF were
      less susceptible to CD4(+)CD25(+) T cell-mediated suppression than were responder
      cells from PB. CONCLUSION: We demonstrate that CD4(+)CD25(+) regulatory T cells
      are present and functional in patients with RA, with higher numbers of regulatory
      T cells with increased suppressive activity found in SF compared with PB. These
      findings suggest a negative feedback system that is active at the site of
      inflammation. The balance between activated responder and regulatory T cells
      appears to influence the extent of immunoregulation in RA.

PMID- 15457446
TI  - Rheumatoid arthritis synovial fluid fibroblasts express TRAIL-R2 (DR5) that is
      functionally active.
AB  - OBJECTIVE: To examine fibroblasts grown from the synovial fluid of rheumatoid
      arthritis (RA) patients for TRAIL-R2 expression, and for susceptibility to
      apoptosis induced by an agonistic anti-TRAIL-R2 monoclonal antibody (mAb).
      METHODS: The expression of TRAIL-R2 (DR5) was determined by flow cytometry on
      fibroblasts grown from the synovial fluid of patients with RA, osteoarthritis
      (OA), seronegative arthritis, and unclassified monarthritis or oligoarthritis,
      and on fibroblasts from the synovial membrane of RA and OA patients.
      Susceptibility to apoptosis mediated by an agonistic anti-TRAIL-R2 mAb was
      determined by alamar blue bioassay, fluorescence microscopy (annexin V/propidium
      iodide staining), and caspase activation. RESULTS: Fibroblasts grew from 35 of 50
      RA synovial fluid samples, of which 26 were DR5(+) (mean [+/-SD] fluorescence
      intensity [MFI] 18.74 +/- 2.5). Fibroblasts also grew from 15 of 30 seronegative
      arthritis synovial fluid samples, 28 of 40 OA synovial fluid samples, and 8 of 20
      unclassified monarthritis or oligoarthritis synovial fluid samples; all of these
      were DR5- (MFI 0.32 +/- 0.02). All 10 of the fibroblast lines from joint
      replacement surgery or synovectomy specimens of RA patients were DR5(+) (MFI 20.3
      +/- 3.2). All fibroblast lines from the synovium of 10 OA patients were DR5-, as
      were fibroblasts from the skin of 5 healthy subjects. DR5(+) fibroblast cultures
      underwent apoptosis when treated in vitro with an agonistic anti-DR5 antibody.
      CONCLUSION: Fibroblasts grown from the synovial fluid and synovial membrane of RA
      patients express TRAIL-R2 that is functionally active. An agonistic anti-TRAIL-R2
      antibody that does not induce hepatocyte toxicity may be an alternative strategy
      for treatment of RA.

PMID- 15457447
TI  - Cooperation of Ras- and c-Myc-dependent pathways in regulating the growth and
      invasiveness of synovial fibroblasts in rheumatoid arthritis.
AB  - OBJECTIVE: To study the specific contribution of MAP kinase activator c-Raf-1 and
      one of its downstream transcription factors, c-Myc, to the growth and invasive
      behavior of rheumatoid arthritis synovial fibroblasts (RASFs). METHODS: RASFs
      were transduced with retroviral constructs expressing dominant-negative mutants
      of c-Raf-1 or c-Myc (DN c-Raf-1 or DN c-Myc, respectively) or with the mock
      vector. The expression of wild-type and mutant proteins was confirmed by Western
      blotting. Growth curves of RASFs were recorded, and apoptosis was measured by
      flow cytometry. Invasiveness of RASFs was assessed in the SCID mouse model of RA.
      Immunohistochemistry was used to study the effects of DN c-Raf-1 on
      phosphorylated c-Jun and matrix metalloproteinase 1 (MMP-1) in RASFs implanted
      into SCID mice. The phosphorylation of ERK and JNK in DN c-Raf-1- and mock
      transduced RASFs was determined in vitro by Western blotting. The levels of MMPs
      in these cells were measured by quantitative polymerase chain reaction (PCR).
      RESULTS: Neither DN c-Raf-1 alone nor DN c-Myc alone significantly altered
      proliferation or apoptosis of RASFs, but both mutants together rapidly induced
      apoptosis. Inhibition of c-Raf-1 or c-Myc significantly reduced the invasiveness
      of RASFs in the SCID mouse model. DN c-Raf-1 decreased the phosphorylation of ERK
      and JNK in vitro and reduced the in vivo expression of phosphorylated c-Jun as
      well as the expression of disease-relevant MMPs. As determined by quantitative
      PCR, the inhibition was most pronounced for MMP-1 and MMP-3. CONCLUSION: The data
      demonstrate that Ras- and c-Myc-dependent signaling events cooperate to regulate
      the growth and invasiveness of RASFs. Targeting of both c-Raf-1 and c-Myc may
      constitute an interesting therapeutic approach in RA.

PMID- 15457448
TI  - Down-regulation of FLIP sensitizes rheumatoid synovial fibroblasts to Fas
      mediated apoptosis.
AB  - OBJECTIVE: Hyperplasia of fibroblast-like synoviocytes (FLS) contributes to
      chronic inflammation and joint destruction in rheumatoid arthritis (RA). FLICE
      inhibitory protein (FLIP) is an antiapoptotic protein that might prevent
      apoptotic elimination of FLS in response to death ligands such as tumor necrosis
      factor alpha (TNFalpha) or Fas ligand, which are present in RA synovium. Previous
      studies on FLIP expression by osteoarthritis (OA) and RA FLS have shown variable
      results, and the specific role of FLIP as an apoptosis inhibitor in these cells
      remains unclear. We undertook this study to investigate the expression and
      antiapoptotic function of FLIP in FLS. METHODS: We studied the expression of FLIP
      by immunohistochemistry and immunoblotting in synovial tissues or cultured FLS
      from RA and OA patients. FLS apoptosis was induced by an agonistic anti-Fas
      monoclonal antibody and FLS were then quantified. We studied the effects of
      cycloheximide (CHX), TNFalpha, and FLIP antisense oligonucleotide on FLIP
      expression and FLS apoptotic susceptibility. RESULTS: FLIP(L) was the isoform
      mainly expressed in lining synoviocytes and cultured FLS. Synovial tissues and
      cultured FLS from OA and RA tissues displayed similar patterns and levels of
      expression of FLIP. Fas-induced apoptosis was variable in different FLS lines,
      but differences between OA and RA groups were not detected. TNFalpha induced
      increases in FLIP(L) and FLIP(S) expression and protected RA FLS from apoptosis,
      while CHX induced the opposite effects. Down-regulation of FLIP by antisense
      oligonucleotide strongly sensitized RA FLS to Fas-mediated apoptosis. CONCLUSION:
      Apoptosis susceptibility and FLIP expression are similar in OA and RA FLS. Down
      regulation of FLIP sensitizes RA FLS to Fas-mediated apoptosis and may be a
      valuable tool for targeting RA FLS hyperplasia.

PMID- 15457449
TI  - Risk factors for symptomatic knee osteoarthritis fifteen to twenty-two years
      after meniscectomy.
AB  - OBJECTIVE: To evaluate the influence of age, sex, body mass index (BMI), extent
      of meniscal resection, cartilage status, and knee load on the development of
      radiographically evident osteoarthritis (OA) of the knee and knee symptoms after
      meniscal resection. METHODS: We evaluated 317 patients with no cruciate ligament
      injury (mean +/- SD age 54 +/- 11 years) who had undergone meniscal resection 15
      22 years earlier (followup rate 70%), with radiographic and clinical examination.
      The Knee injury and Osteoarthritis Outcome Score was used to quantify knee
      related symptoms. Sixty-eight unoperated subjects identified from national
      population records were included as a reference group. RESULTS: Symptomatic
      radiographic OA (corresponding to Kellgren/Lawrence grade > or =2) was present in
      83 of 305 operated knees (27%) and 7 of 68 control knees (10%) (relative risk
      2.6, 95% confidence interval [95% CI] 1.3-6.1). Patients who had undergone total
      meniscectomy and subjects with obesity (BMI > or =30) had a greater likelihood of
      tibiofemoral radiographic OA than those who had undergone partial meniscal
      resection and those with a BMI <25, respectively. Furthermore, degenerative
      meniscal tear, intraoperative cartilage changes, and lateral meniscectomy were
      associated with radiographic OA more frequently than were longitudinal tear,
      absence of cartilage changes, and medial meniscectomy, respectively. Symptomatic
      tibiofemoral or patellofemoral radiographic OA was associated with obesity,
      female sex, and degenerative meniscal tear. CONCLUSION: Contributing risk factors
      for OA development after meniscal resection are similar to risk factors for
      common knee OA. Systemic factors and local biomechanical factors interact.
      Obesity, female sex, and preexisting early-stage OA are features associated with
      poor self-reported and radiographic outcome. Partial meniscal resection is
      associated with less radiographic OA over time than is total meniscectomy.

PMID- 15457450
TI  - Age dependency of cartilage magnetic resonance imaging T2 relaxation times in
      asymptomatic women.
AB  - OBJECTIVE: Because the magnetic resonance imaging (MRI) transverse relaxation
      time (T2) of cartilage is sensitive to organization of collagen fibers in the
      cartilage, it may be a noninvasive image marker for senescent changes in
      cartilage collagen and early cartilage degeneration. The purpose of this study
      was to determine age-dependent differences in cartilage T2 values in healthy
      asymptomatic women. METHODS: Quantitative T2 maps of patellar cartilage from 30
      asymptomatic women ages 22-86 years were obtained using a 3.0T MRI scanner. The
      study population was stratified by age into 4 cohorts: 18-30, 31-45, 46-65, and
      66-86 years. Spatial differences in cartilage T2 were determined as a function of
      normalized distance from bone. Older groups were compared with the 18-30-year-old
      group to determine the effects of age on cartilage T2 values. Regions were
      considered statistically significantly different if the mean T2 values between
      groups differed at P < 0.05. RESULTS: Mean cartilage T2 profiles were nearly
      identical for the 2 youngest cohorts. Compared with the 18-30-year-old group, T2
      values were statistically significantly longer in the superficial 40% of
      cartilage in the 46-65-year-old group and over the entire cartilage thickness in
      the 66-86-year-old group. CONCLUSION: The location of T2 elevations in women over
      the age of 45 years is consistent with the theory that senescent changes of
      cartilage collagen begin near the articular surface and progress to the deeper
      cartilage with advancing age.

PMID- 15457451
TI  - Up-regulation of microsomal prostaglandin E synthase 1 in osteoarthritic human
      cartilage: critical roles of the ERK-1/2 and p38 signaling pathways.
AB  - OBJECTIVE: Microsomal prostaglandin E synthase 1 (mPGES-1) is the final enzyme of
      the cascade that produces prostaglandin E(2) (PGE(2)), a key actor in arthritis.
      To study mPGES-1 synthesis in human cartilage and its regulation by interleukin
      1beta (IL-1beta), we used human cartilage and an immortalized human chondrocyte
      cell line. Furthermore, we investigated the signaling pathways involved in mPGES
      1 expression. METHODS: We used real-time quantitative reverse transcription
      polymerase chain reaction, Northern blotting, and Western blotting to measure
      mPGES-1 messenger RNA (mRNA) and protein expression in human chondrocytes. PGE(2)
      production was measured by enzyme-linked immunosorbent assay. RESULTS: Cartilage
      specimens from osteoarthritis (OA) patients contained far greater amounts of
      mPGES-1 and cyclooxygenase 2 (COX-2) mRNA than did normal cartilage. Incubation
      with IL-1beta markedly increased mPGES-1 mRNA and protein in a dose-dependent and
      time-dependent manner, in parallel with an increase in PGE(2) levels. Both
      PD98059, an ERK pathway inhibitor, and SB203580, a p38alpha/beta MAPK inhibitor,
      abolished the increases in mPGES-1 mRNA and protein in response to IL-1beta. The
      specific p38alpha MAPK inhibitor SC906 suppressed IL-1beta-induced COX-2
      expression but not IL-1beta-induced mPGES-1 expression, suggesting preferential
      involvement of p38beta MAPK in IL-1beta-induced mPGES-1 expression. CONCLUSION:
      This study is the first to show that mPGES-1 is stimulated in human chondrocytes
      by the proinflammatory cytokine IL-1beta via activation of both ERK-1/2 and p38
      MAPK in an isoform-specific manner. We postulate that mPGES-1 may be a novel
      target for OA therapy.

PMID- 15457452
TI  - Release of hyaluronan and hyaladherins (aggrecan G1 domain and link proteins)
      from articular cartilage exposed to ADAMTS-4 (aggrecanase 1) or ADAMTS-5
      (aggrecanase 2).
AB  - OBJECTIVE: To determine whether aggrecanase (ADAMTS) activities in articular
      cartilage can directly lead to the release of hyaluronan (HA) and hyaladherins
      (aggrecan G1 domain and link proteins), as may occur ex vivo during stimulation
      of cartilage explants with interleukin-1 (IL-1) or retinoic acid or in vivo in
      synovial joints during aging and joint pathology. METHODS: Bovine articular
      cartilage discs (live or freeze-killed) were cultured in the presence of IL-1 or
      were incubated in digestion buffer containing recombinant human ADAMTS-4
      (rHuADAMTS-4; aggrecanase 1) or rHuADAMTS-5 (aggrecanase 2). Culture media,
      digestion supernatants, and tissue extracts were assayed for sulfated
      glycosaminoglycan (sGAG) content and analyzed by Western blotting to detect
      aggrecanase-generated G1 domain (using neoepitope monoclonal antibody AGG-C1/anti
      NITEGE(373)) and link proteins (using monoclonal antibody 8-A-4), as well as by
      quantitative enzyme-linked immunosorbent assays to detect aggrecanase-generated
      G1 domain (G1-NITEGE(373)) and HA. RESULTS: IL-1 treatment of live cartilage
      explants induced a time-dependent release of sGAG, aggrecanase-generated G1
      domain (G1-NITEGE(373)), and HA into the culture media. Exposure of live or
      freeze-killed articular cartilage discs to rHuADAMTS-4 or rHuADAMTS-5 resulted in
      a dose- and time-dependent release of sGAG and hyaluronan from the tissue,
      accompanied by a concomitant release of functionally intact hyaladherins
      (aggrecan G1-NITEGE(373) and link proteins). CONCLUSION: Coincident with
      aggrecanolysis, aggrecanase activities in articular cartilage may actuate the
      release of HA and associated hyaladherins, thereby further compromising the
      integrity of the cartilage matrix during degenerative joint diseases such as
      osteoarthritis.

PMID- 15457453
TI  - Synthesis of proteoglycan 4 by chondrocyte subpopulations in cartilage explants,
      monolayer cultures, and resurfaced cartilage cultures.
AB  - OBJECTIVE: To quantify the levels of proteoglycan 4 (PRG4) expression by
      subpopulations of chondrocytes from superficial, middle, and deep layers of
      normal bovine calf cartilage in various culture systems. METHODS: Bovine calf
      articular cartilage discs or isolated cells were used in 1 of 3 systems of
      chondrocyte culture: explant, monolayer, or transplant, for 1-9 days. PRG4
      expression was quantified by enzyme-linked immunosorbent assay of spent medium
      and localized by immunohistochemistry at the articular surface and within
      chondrocytes in explants and cultured cells. RESULTS: Superficial chondrocytes
      secreted much more PRG4 than did middle and deep chondrocytes in all cultures.
      The pattern of PRG4 secretion into superficial culture medium varied with the
      duration of culture, decreasing with time in explant culture (from approximately
      25 microg/cm(2)/day on days 0-1 to approximately 3 microg/cm(2)/day on days 5-9),
      while increasing in monolayer culture (from approximately 1 pg/cell/day on days 0
      1 to approximately 7 pg/cell/day on days 7-9) and tending to increase in
      transplant culture (reaching approximately 2 microg/cm(2)/day by days 7-9). In
      all of the culture systems, inclusion of ascorbic acid stimulated PRG4 secretion,
      and the source of PRG4 was immunolocalized to superficial cells. CONCLUSION: The
      results described here indicate that the phenotype of PRG4 secretion by
      chondrocytes in culture is generally maintained, in that PRG4 is expressed to a
      much greater degree by chondrocytes from the superficial zone than by those from
      the middle and deep zones. The marked up-regulation of PRG4 synthesis by ascorbic
      acid may have implications for cartilage homeostasis and prevention of
      osteoarthritic disease. Transplanting specialized cells that secrete PRG4 to a
      surface may impart functional lubrication and be generally applicable to many
      tissues in the body.

PMID- 15457454
TI  - Platelet-activating factor-acetylhydrolase and other novel risk and protective
      factors for cardiovascular disease in systemic lupus erythematosus.
AB  - OBJECTIVE: There is an important inflammatory component to atherosclerosis and
      cardiovascular disease (CVD). It is therefore interesting that the risk of CVD is
      high in inflammatory diseases such as systemic lupus erythematosus (SLE). In this
      study, we investigated nontraditional risk factors for the development of CVD in
      patients with SLE. METHODS: Twenty-six women (mean age 52 years) with SLE and a
      history of CVD were compared with 26 age-matched women with SLE and no clinical
      manifestations of CVD (SLE controls) and 26 age-matched healthy women (population
      controls). Serum levels of several novel nontraditional risk and protective
      factors were determined: heat-shock protein (HSP)-related factors (Hsp60, Hsp70,
      anti-human Hsp60, anti-human Hsp70, and anti-mycobacterial Hsp65), platelet
      activating factor-acetylhydrolase (PAF-AH) activity, secretory phospholipase A(2)
      GIIA (sPLA(2)), and anti-endothelial cell antibody (AECA). The intima-media
      thickness and the presence of plaques in the common carotid arteries were
      determined by B-mode ultrasound as a surrogate measure of atherosclerosis.
      RESULTS: Levels of PAF-AH, but not HSP-related factors, AECA, or sPLA(2), were
      significantly increased in SLE cases. Only PAF-AH discriminated between SLE cases
      and SLE controls (P = 0.005). PAF-AH was significantly associated with low
      density lipoprotein (LDL) cholesterol and total cholesterol in the SLE cases (r =
      0.50, P = 0.0093 and r = 0.54, P = 0.0045), but not in either control group.
      CONCLUSION: The increased levels of PAF-AH in SLE cases and the association
      between PAF-AH and LDL cholesterol adds support to the notion that PAF-AH may
      promote atherothrombosis in SLE. The role of HSPs in CVD is complex, since anti
      Hsp65 appears to be associated with the presence of CVD, whereas Hsp70 might
      protect against it. In this cross-sectional study, levels of HSP-related factors,
      AECA, and sPLA(2) were not associated with CVD in SLE.

PMID- 15457455
TI  - Selective gray matter damage in neuropsychiatric lupus.
AB  - OBJECTIVE: Damage of brain parenchyma in patients with primary diffuse
      neuropsychiatric systemic lupus erythematosus (NPSLE) has been indicated by
      magnetization transfer imaging (MTI). However, the location of MTI abnormalities
      is unknown. This study was undertaken to assess the distribution of MTI
      abnormalities over gray matter (GM) and white matter (WM) in SLE patients with a
      history of NP symptoms without explanatory magnetic resonance imaging (MRI)
      evidence of focal disease. METHODS: MTI was performed in 24 female SLE patients
      with a history of diffuse NP symptoms and 24 healthy female controls.
      Magnetization transfer ratio (MTR) maps were calculated for GM and WM separately,
      and GM and WM MTR histograms were generated. Univariate and multivariate analyses
      with age as an additional covariate were performed on the histogram parameters
      peak location (PL), peak height (PH), and mean MTR. RESULTS: Compared with
      controls, significantly reduced PH (mean +/- SD 136 +/- 22 arbitrary units versus
      151 +/- 13 arbitrary units) and mean MTR (33.3 +/- 1.0 percent units versus 33.6
      +/- 0.5 percent units) were found in the GM of NPSLE patients (P = 0.002 and P =
      0.033, respectively, in multivariate analyses). No significant differences were
      observed for WM MTR parameters. CONCLUSION: This is the first study to
      demonstrate, using MTI, that in SLE patients with a history of NP symptoms and
      without explanatory focal abnormalities on MRI, the GM is particularly affected.
      These findings support the hypothesis that neuronal injury may underlie central
      nervous system manifestations in NPSLE.

PMID- 15457456
TI  - Expression of chemokine and fibrosing factor messenger RNA in the urinary
      sediment of patients with lupus nephritis.
AB  - OBJECTIVE: Lupus nephritis is characterized by intrarenal inflammation. To assess
      the extent and severity of disease activity and renal involvement, this study
      examined the expression of transforming growth factor beta (TGFbeta) and monocyte
      chemoattractant protein 1 (MCP-1) in the urinary sediment of patients with
      systemic lupus erythematosus (SLE). METHODS: We studied 106 patients with SLE who
      were classified according to their disease status as those with active disease,
      those with disease in remission, and those with nonrenal SLE. Ten healthy
      subjects were used as controls. Lupus activity was assessed by the SLE Disease
      Activity Index (SLEDAI). If renal biopsy was performed, the histologic activity
      index and chronicity index were determined, and a morphometry analysis of renal
      scarring was performed. The urinary expresssion of TGFbeta and MCP-1 messenger
      RNA (mRNA) was studied by real-time quantitative polymerase chain reaction, and
      the corresponding protein concentrations of TGFbeta and MCP-1 in the urine were
      measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Expression of
      TGFbeta and MCP-1 mRNA in the urinary sediment was significantly elevated in the
      active disease group (P < 0.001 for both). These expression levels of TGFbeta and
      MCP-1 mRNA correlated with the SLEDAI score (TGFbeta r = 0.71, P < 0.001; MCP-1 r
      = 0.72, P < 0.001), and also significantly correlated with the histologic
      activity index (TGFbeta r = 0.487, P = 0.004; MCP-1 r = 0.357, P = 0.038). The
      urinary protein concentration of MCP-1, but not of TGFbeta, correlated with the
      SLEDAI score (r = 0.66, P < 0.001). However, neither the protein concentration of
      TGFbeta nor that of MCP-1 as measured by ELISA in the urine correlated with the
      histologic activity index. CONCLUSION: The measurement of urinary mRNA expression
      may be a noninvasive method for the assessment of lupus disease activity and the
      severity of renal involvement in patients with lupus nephritis.

PMID- 15457458
TI  - Evidence for coxsackievirus infection in primary Sjogren's syndrome.
AB  - OBJECTIVE: Primary Sjogren's syndrome (SS) is an autoimmune disease characterized
      by activation of minor salivary gland (MSG) epithelial cells and B and T
      lymphocytic infiltrates. These findings have long encouraged the hypothesis that
      a persistent viral infection of the MSG epithelial cells may drive the autoimmune
      response; however, the identity of that virus has remained elusive. The aim of
      this study was to test this hypothesis. METHODS: We applied the differential
      display protocol to MSG RNA samples from patients with primary SS and healthy
      controls. We then used seminested reverse transcriptase-polymerase chain reaction
      to amplify the 5'-noncoding region (5'-NCR) of the enteroviral genome in 8
      patients with primary SS, 9 patients with secondary SS, and 8 control subjects.
      Immunohistochemistry was performed to study the expression of the VP1 enteroviral
      capsid protein in MSG biopsy samples from 12 patients with primary SS, 8 patients
      with secondary SS, and 16 controls. RESULTS: Differential display analysis
      yielded a 94-bp fragment of coxsackievirus B4 (CVB4) P2A gene in the primary SS
      samples. The 5'-NCR was amplified in 7 samples from patients with primary SS and
      in no samples from patients with secondary SS or controls. The 7 amplified
      products were sequenced; 4 of the sequences were found to be 98-99% identical to
      the 5'- NCR of CVB4, and 3 were found to be 97-98% identical to the 5'-NCR of
      CVA13. Immunohistochemistry for the enteroviral capsid protein VP1 revealed
      positive staining in epithelial cells and lymphocytic infiltrates in 11 primary
      SS samples, 1 secondary SS sample, and no control samples. CONCLUSION: We provide
      evidence that primary SS may be associated with coxsackievirus infection of the
      MSG epithelial cells and focal lymphocytic infiltrates. Our findings are
      formulated in a hypothesis concerning the possible role of coxsackieviruses in
      the induction and maintenance of autoimmunity in primary SS.

PMID- 15457457
TI  - U1 RNA induces innate immunity signaling.
AB  - OBJECTIVE: The U1-70-kd RNP is a prominent target of autoimmunity in connective
      tissue diseases. In this study, we explored whether its endogenous ligand, U1
      RNA, mediates a proimmune signal and may be immunogenic. METHODS: We assayed the
      proliferation of control and MyD88-knockout splenocytes in response to in vitro
      synthesized U1 RNA, and measured interleukin-6 (IL-6) and IL-8 secretion induced
      by U1 RNA in a human cell line competent for signaling through Toll-like receptor
      3 (TLR-3) and TLR-5. RESULTS: Treatment with U1 RNA or with poly(I-C), a known
      agonist of TLR-3, induced approximately twice as much control splenocyte
      proliferation as did treatment with RNase-digested U1 RNA. Proliferation in
      response to either poly(I-C) or U1 RNA by MyD88-knockout splenocytes was
      similarly attenuated. Similar to poly(I-C), U1 RNA induced significant secretion
      of both IL-6 and IL-8 from a TLR-3-expressing human cell line; in contrast, the
      TLR-5 agonist flagellin induced predominantly IL-8 secretion. Pretreatment of U1
      RNA with RNase abolished IL-6 and IL-8 secretion. CONCLUSION: U1 RNA is capable
      of inducing manifestations consistent with TLR-3 activation. The ability of U1
      RNA (which has a substantial double-stranded secondary structure) to activate TLR
      3 may contribute to the immunogenicity of the U1-70-kd autoantigen. Stimulation
      of innate immunity by native RNA molecules with a double-stranded secondary
      structure may help explain the high prevalence of autoimmunity to RNA binding
      proteins.

PMID- 15457459
TI  - Effective treatment of a mouse model of Sjogren's syndrome with eyedrop
      administration of anti-CD4 monoclonal antibody.
AB  - OBJECTIVE: To determine whether eyedrop administration of an anti-CD4 monoclonal
      antibody (mAb) is effective in the treatment of Sjogren's syndrome (SS) using a
      mouse model of the disease. METHODS: The anti-CD4 mAb was administered daily into
      the eyes of mice with SS from ages 4 to 8 weeks or ages 10 to 12 weeks. During
      treatment, tear volume was monitored and after final treatment, histologic
      features of the lacrimal and salivary glands, the phenotypes and function of T
      cells, and serum titers of anti-alpha-fodrin antibody were examined. RESULTS:
      Eyedrop administration of anti-CD4 mAb before the onset of SS prevented the
      autoimmune pathology seen in the lacrimal glands but not that in the salivary
      glands. Furthermore, eyedrop administration of anti-CD4 mAb after the development
      of SS inhibited mononuclear cell infiltration and the destruction of parenchyma
      only in the lacrimal glands. Eyedrop administration of anti-CD4 mAb suppressed
      the local activation of CD4+ T cells rather than deleting CD4+ T cells, which
      reduced the expansion of pathologic CD4+ T cells against alpha-fodrin.
      CONCLUSION: These results demonstrate the remarkable efficacy of anti-CD4 mAb
      eyedrops in the treatment of SS eye symptoms, which illustrates a new antibody
      based therapeutic strategy for patients with eye problems caused by SS as well as
      other diseases.

PMID- 15457460
TI  - Intracellular events in platelet activation induced by antiphospholipid
      antibodies in the presence of low doses of thrombin.
AB  - OBJECTIVE: Thrombosis and thrombocytopenia are features of the antiphospholipid
      syndrome (APS), suggesting that antiphospholipid antibodies (aPL) may bind
      platelets, causing activation and aggregation of platelets and thrombosis. The
      intracellular events involved in aPL-mediated platelet activation are not fully
      understood and are therefore the subject of this study. METHODS: IgG fractions
      and their F(ab')(2) fragments were purified from the sera of 7 patients with APS
      and from the pooled sera of 10 healthy subjects (as controls). Phosphorylation of
      p38 MAPK, ERK-1/2, and [Ca(2+)]-dependent cytosolic phospholipase A(2) (cPLA(2))
      was determined in lysates of washed platelets pretreated with low doses of
      thrombin and aPL or control IgG or their F(ab')(2) fragments, by immunoblot. The
      effects of aPL on platelet aggregation in the presence or absence of a p38 MAPK
      inhibitor, SB203580, were examined. Thromboxane B(2) (TXB(2)) production was
      detected by enzyme-linked immunosorbent assay on gel-filtered platelets treated
      with aPL and thrombin, with or without SB203580. Calcium mobilization studies
      were done utilizing a fluorometric assay. RESULTS: Treatment of platelets with
      IgG aPL, or their F(ab')(2) fragments, in conjunction with subactivating doses of
      thrombin resulted in a significant increase in phosphorylation of p38 MAPK.
      Neither the IgG aPL nor their F(ab')(2) fragments increased significantly the
      phosphorylation of ERK-1/2 MAPKs. Furthermore, pretreatment of platelets with
      SB203580 completely abrogated the aPL-mediated enhanced aggregation of the
      platelets. Platelets treated with F(ab')(2) aPL and thrombin produced
      significantly larger amounts of TXB(2) when compared with controls, and this
      effect was completely abrogated by treatment with SB203580. In addition, cPLA(2)
      was also significantly phosphorylated in platelets treated with thrombin and
      F(ab')(2) aPL. There were no significant changes in intracellular [Ca(2+)] when
      platelets were treated with aPL and low doses of thrombin. CONCLUSION: The data
      strongly indicate that aPL in the presence of subactivating doses of thrombin
      induce the production of TXB(2) mainly through the activation of p38 MAPK and
      subsequent phosphorylation of cPLA(2). The ERK-1/2 pathway does not seem to be
      involved in this process, at least in the early stages of aPL-mediated platelet
      activation.

PMID- 15457461
TI  - A genome-wide scan for juvenile rheumatoid arthritis in affected sibpair families
      provides evidence of linkage.
AB  - OBJECTIVE: Juvenile rheumatoid arthritis (JRA) represents a heterogeneous group
      of disorders with a complex genetic component. A genome scan was performed to
      detect linkage to JRA in 121 families containing 247 affected children in North
      America (the JRA Affected Sibpair [ASP] Registry). METHODS: Genotype data
      collected for HLA-DR and 386 microsatellite markers were subjected to multipoint
      nonparametric linkage analysis. Following analysis of the entire set of families,
      additional analyses were performed after a priori stratification by disease onset
      type, age at onset, disease course, and selected HLA-DRB1 alleles. RESULTS:
      Linkage of JRA to the HLA region was confirmed (logarithm of odds [LOD] score
      2.26). Additional evidence supporting linkage of JRA was observed at 1p36
      (D1S214; LOD 1.65), 19p13 (D19S216; LOD 1.72), and 20q13 (D20S100; LOD 1.75). For
      early-onset polyarticular disease, evidence of linkage was found at chromosome
      7q11 (D7S502; LOD 3.47). For pauciarticular disease, evidence supporting linkage
      was observed on chromosome 19p13 (D19S216; LOD 2.98), the same marker that
      supported linkage to the "JRA" phenotype. Other regions supporting linkage with
      JRA disease subtype included 20q13, 4q24, 12q24, and Xp11. Stratification of
      families based on the presence of the HLA-DR8 allele in affected siblings
      resulted in significant linkage observed at 2p25 (D2S162/D2S305; LOD 6.0).
      CONCLUSION: These data support the hypothesis that multiple genes, including at
      least 1 in the HLA region, influence susceptibility to JRA. These findings for
      JRA are consistent with findings for other autoimmune diseases and support the
      notion that common genetic regions contribute to an autoimmune phenotype.

PMID- 15457462
TI  - Diagnostic classification of spondylarthropathy and rheumatoid arthritis by
      synovial histopathology: a prospective study in 154 consecutive patients.
AB  - OBJECTIVE: To explore prospectively the value of synovial histopathology in
      comparison with the value of classic parameters for diagnostic classification of
      spondylarthropathy (SpA) and rheumatoid arthritis (RA) in patients with an
      atypical disease presentation. METHODS: Synovial biopsy samples were obtained
      from 154 consecutive patients presenting for diagnostic evaluation; 67 patients
      fulfilled the classification criteria for RA, SpA, or other well-defined disease
      at the time of arthroscopy (cohort 1), and an additional 53 patients were
      classified after a full diagnostic reevaluation at 6 months (cohort 2). Synovial
      parameters with diagnostic value were identified in cohort 1 and were compared
      prospectively with classic diagnostic parameters in cohort 2. RESULTS: Staining
      with anticitrulline, staining with monoclonal antibody 12A (recognizing HLA-DR
      shared epitope-human cartilage glycoprotein 39(263-275) complexes), and crystal
      deposition had positive predictive values (PPVs) for diagnosis of >90% in
      patients with an atypical disease presentation (cohort 2). Using these 3
      parameters, a diagnosis was predicted by synovial histopathology in 39.6% of
      cohort 2 patients and turned out to be correct in 90.5% of these patients at 6
      months of followup. Using a multiparameter model rather than single
      histopathologic parameters, even better results were obtained, with a diagnostic
      prediction in 79.2% of samples and a PPV of 81.0%. In comparison, a similar
      multiparameter model using classic diagnostic criteria rather than synovial
      histopathology performed poorly in cohort 2; the sensitivity was 56.6% and the
      PPV was 73.3%, with an inferior capacity to predict SpA. Especially for the
      presence of crystals and anticitrulline staining, the analysis of synovial tissue
      had a clear added value to the analysis of synovial fluid or serum in patients
      with an atypical presentation. CONCLUSION: This proof-of-concept study indicates
      that synovial histopathology can contribute to the multiparametric diagnostic
      classification of inflammatory arthritis in patients with an atypical
      presentation.

PMID- 15457463
TI  - Involvement of matrix metalloproteinases and their inhibitors in peripheral
      synovitis and down-regulation by tumor necrosis factor alpha blockade in
      spondylarthropathy.
AB  - OBJECTIVE: To investigate the role of matrix metalloproteinases (MMPs) and tissue
      inhibitors of matrix metalloproteinases (TIMPs) in spondylarthropathy (SpA)
      synovitis. METHODS: Paired samples of synovial biopsy tissue as well as serum and
      synovial fluid (SF) from 41 patients with SpA and 20 patients with rheumatoid
      arthritis (RA) and serum samples from 20 healthy controls were analyzed by
      immunohistochemistry and enzyme-linked immunosorbent assay for the presence of
      MMPs 1, 2, 3, and 9 and TIMPs 1 and 2. In addition, sera from 16 patients with
      ankylosing spondylitis (AS) and peripheral synovitis and 17 patients with AS and
      exclusively axial involvement were analyzed. An additional cohort of SpA patients
      was analyzed at baseline and after 12 weeks of infliximab treatment. RESULTS:
      Staining for MMPs and TIMPs showed a cellular and interstitial pattern in the
      synovial lining and sublining layers that was similar between the RA and SpA
      patients. Involvement of MMPs and TIMPs in SpA synovitis was suggested by the
      correlation with cellular infiltration, vascularization, and cartilage
      degradation. Higher serum levels of MMPs 3 and 9 were revealed in SpA and RA
      patients as compared with healthy controls. Production of MMP-3, but not MMP-9,
      in the serum reflected the presence of peripheral synovitis, as indicated by 1)
      the correlation between serum levels, SF levels (which were 1,000-fold higher
      than the serum levels), and synovial expression of MMP-3, 2) the increased levels
      of MMP-3 in AS patients with peripheral disease and not exclusively axial
      involvement, and 3) the correlation of serum and SF MMP-3 with parameters of
      synovial, but not systemic, inflammation. The modulation of the MMP/TIMP system
      by tumor necrosis factor alpha (TNFalpha) blockade was confirmed by the down
      regulation of all MMPs and TIMPs in the synovium and a pronounced and rapid
      decrease of serum MMP-3. CONCLUSION: MMPs and TIMPs are highly expressed in SpA
      synovitis and mirror both the inflammatory and tissue-remodeling aspects of the
      local disease process. Serum MMP-3, originating from the inflamed joint,
      represents a valuable biomarker for peripheral synovitis. Modulation of the
      MMP/TIMP system by infliximab could contribute to the antiinflammatory and tissue
      remodeling effects of TNFalpha blockade in SpA.

PMID- 15457464
TI  - Antineutrophil cytoplasmic antibodies reacting with human neutrophil elastase as
      a diagnostic marker for cocaine-induced midline destructive lesions but not
      autoimmune vasculitis.
AB  - OBJECTIVE: Human neutrophil elastase (HNE) and proteinase 3 (PR3) are
      structurally and functionally related. PR3 is the prominent target antigen for
      antineutrophil cytoplasmic antibodies (ANCAs) in Wegener's granulomatosis (WG).
      Reported frequencies of HNE ANCAs in WG and other autoimmune diseases range from
      0% to 20%. We previously detected HNE ANCAs in patients with cocaine-induced
      midline destructive lesions (CIMDL). We tested the hypothesis that discrepancies
      in the reported frequencies of HNE ANCAs in patients with vasculitis may be
      related to differences in detection methods, and that HNE ANCA may be a marker
      for CIMDL. METHODS: HNE ANCA reactivity in 25 patients with CIMDL was
      characterized and compared with that in a control cohort of 604 consecutive
      patients (64 with WG, 14 with microscopic polyangiitis [MPA], and 526 others) and
      45 healthy volunteers. HNE ANCAs were measured by indirect immunofluorescence
      using a previously undescribed expression system for recombinant HNE and by
      direct and capture enzyme-linked immunosorbent assays using purified native HNE
      as target antigen. RESULTS: Among patients with CIMDL, HNE ANCAs were detectable
      by 1 assay in 84%, by 2 assays in 68%, and by all 3 assays in 36%. Fifty-seven
      percent of HNE ANCA-positive CIMDL sera were also PR3 ANCA-positive by at least 1
      assay. In contrast, only 8 (1.3%) of 604 control sera reacted with HNE in at
      least 1 assay, 3 (0.5%) reacted in 2 assays, and only 1 serum sample (0.16%)
      reacted in all 3 assays. Sera obtained from patients with WG or MPA were
      universally HNE ANCA-negative, as were sera obtained from healthy controls.
      CONCLUSION: Optimal sensitivity for HNE ANCA requires multimodality testing. HNE
      ANCAs are frequent in CIMDL but not in other autoimmune diseases, including
      classic ANCA-associated vasculitis. HNE ANCAs may discriminate between CIMDL and
      WG, whereas a positive test result for PR3 ANCA may not.

PMID- 15457465
TI  - First report of systemic reactive (AA) amyloidosis in a patient with the
      hyperimmunoglobulinemia D with periodic fever syndrome.
AB  - Systemic reactive (AA) amyloidosis, leading to renal failure, is a severe
      complication of most hereditary periodic fever syndromes. The risk of developing
      this life-threatening condition varies widely among these disorders, being higher
      for patients affected by familial Mediterranean fever and tumor necrosis factor
      receptor-associated periodic syndrome. In spite of an acute-phase response during
      attacks, amyloidosis has never, to date, been described in patients affected with
      the hyperimmunoglobulinemia D with periodic fever syndrome (HIDS). This is the
      first report to describe the occurrence of renal AA amyloidosis causing severe
      nephrotic syndrome in a young Italian man affected with HIDS. The diagnosis of
      HIDS was established according to clinical, laboratory, and genetic criteria as
      required by the international Nijmegen HIDS registry. In this patient, 2
      mutations in the mevalonate kinase gene were identified, one of which, the
      leucine-to-arginine substitution at codon 265, is novel.

PMID- 15457466
TI  - Successful treatment of SAPHO syndrome with zoledronic acid.
AB  - The SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, and osteitis) is a
      chronic, relapsing, inflammatory condition with skin and osteoarticular
      manifestations. Its etiology remains unclear, and various treatment regimens with
      steroids and nonsteroidal antiinflammatory drugs frequently fail to control the
      disease, while exposing patients to the side effects of these drugs. Because the
      SAPHO syndrome manifests as a destructive inflammatory bone disease, use of
      bisphosphonates that possess antiosteoclastic and probably antiinflammatory
      properties has been suggested to be helpful. To our knowledge, this is the first
      reported case of successful treatment with zoledronic acid of SAPHO syndrome that
      was resistant to conventional treatment.

PMID- 15457467
TI  - A double-blind, multicenter trial comparing duloxetine with placebo in the
      treatment of fibromyalgia patients with or without major depressive disorder.
AB  - OBJECTIVE: To assess the efficacy and safety of duloxetine, a serotonin and
      norepinephrine reuptake inhibitor, in subjects with primary fibromyalgia, with or
      without current major depressive disorder. METHODS: This study was a randomized,
      double-blind, placebo-controlled trial conducted in 18 outpatient research
      centers in the US. A total of 207 subjects meeting the American College of
      Rheumatology criteria for primary fibromyalgia were enrolled (89% female, 87%
      white, mean age 49 years, 38% with current major depressive disorder). After
      single-blind placebo treatment for 1 week, subjects were randomly assigned to
      receive duloxetine 60 mg twice a day (n = 104) or placebo (n = 103) for 12 weeks.
      Co-primary outcome measures were the Fibromyalgia Impact Questionnaire (FIQ)
      total score (score range 0-80, with 0 indicating no impact) and FIQ pain score
      (score range 0-10). Secondary outcome measures included mean tender point pain
      threshold, number of tender points, FIQ fatigue, tiredness on awakening, and
      stiffness scores, Clinical Global Impression of Severity (CGI-Severity) scale,
      Patient Global Impression of Improvement (PGI-Improvement) scale, Brief Pain
      Inventory (short form), Medical Outcomes Study Short Form 36, Quality of Life in
      Depression Scale, and Sheehan Disability Scale. RESULTS: Compared with placebo
      treated subjects, duloxetine-treated subjects improved significantly more (P =
      0.027) on the FIQ total score, with a treatment difference of -5.53 (95%
      confidence interval -10.43, -0.63), but not significantly more on the FIQ pain
      score (P = 0.130). Compared with placebo-treated subjects, duloxetine-treated
      subjects had significantly greater reductions in Brief Pain Inventory average
      pain severity score (P = 0.008), Brief Pain Inventory average interference from
      pain score (P = 0.004), number of tender points (P = 0.002), and FIQ stiffness
      score (P = 0.048), and had significantly greater improvement in mean tender point
      pain threshold (P = 0.002), CGI-Severity (P = 0.048), PGI-Improvement (P =
      0.033), and several quality-of-life measures. Duloxetine treatment improved
      fibromyalgia symptoms and pain severity regardless of baseline status of major
      depressive disorder. Compared with placebo-treated female subjects (n = 92),
      duloxetine-treated female subjects (n = 92) demonstrated significantly greater
      improvement on most efficacy measures, while duloxetine-treated male subjects (n
      = 12) failed to improve significantly on any efficacy measure. The treatment
      effect on significant pain reduction in female subjects was independent of the
      effect on mood or anxiety. Duloxetine was safely administered and well tolerated.
      CONCLUSION: In this randomized, controlled, 12-week trial (with a 1-week placebo
      lead-in phase), duloxetine was an effective and safe treatment for many of the
      symptoms associated with fibromyalgia in subjects with or without major
      depressive disorder, particularly for women, who had significant improvement
      across most outcome measures.

PMID- 15457468
TI  - The etiologic diagnosis of infectious discitis is improved by amplification-based
      DNA analysis.
AB  - OBJECTIVE: Blood cultures and cultures of disc material are required to identify
      and treat bacterial agents responsible for septic spondylodiscitis, but these
      methods have limited sensitivities. We undertook this study to compare nonculture
      amplification-based DNA analysis with conventional culture of disc aspirate.
      METHODS: Nineteen patients with spondylodiscitis, including 11 with a history of
      spinal surgery, presented with negative blood cultures and underwent percutaneous
      disc or epidural abscess puncture for bacterial diagnosis. Amplification by
      polymerase chain reaction was performed on 16S ribosomal DNA universal target
      genes and femA staphylococci-specific target genes in all patients, and on the
      upstream p34 mycobacterial gene in 1 patient. Species identification relied on
      amplicon sequencing and comparison with templates from GenBank. Amplification of
      the femA gene led to subsequent testing for methicillin resistance by
      amplification of the mecA gene. Further assessment using a staphylococci- and
      methicillin resistance-specific DNA array was performed on 3 samples. RESULTS:
      Microbiologic and molecular assays identified the causative organism in 14 of 19
      patients (74%) and 19 of 19 patients (100%), respectively. In culture-positive
      patients, DNA-based and microbiologic results were highly correlated. Five agents
      (Staphylococcus simulans, Staphylococcus sciuri, Brucella species, Actinomyces
      israelii, and Mycobacterium tuberculosis complex) were identified only by DNA
      based methods. In 1 sample, Corynebacterium jeikeium and coagulase-negative
      Staphylococcus were both cultured, whereas DNA analysis identified only
      Staphylococcus hominis. CONCLUSION: DNA-based methods are highly sensitive and
      specific. They can usefully complement standard microbiologic methods for
      identifying the cause of infectious spondylodiscitis and contribute to species
      specific therapeutic orientation in patients with negative blood and disc
      aspirate cultures.

PMID- 15457469
TI  - Triptolide, an active component of the Chinese herbal remedy Tripterygium
      wilfordii Hook F, inhibits production of nitric oxide by decreasing inducible
      nitric oxide synthase gene transcription.
AB  - OBJECTIVE: The ethyl acetate (EA) extract of Tripterygium wilfordii Hook F (TWHF)
      and its major active component, triptolide, have been reported to be effective in
      the treatment of rheumatoid arthritis and other autoimmune inflammatory diseases.
      Nitric oxide (NO) has been recognized as an important mediator of inflammation.
      This study was therefore undertaken to examine the effects of the EA extract and
      triptolide on the production of NO and inducible NO synthase (iNOS) gene
      expression and transcription in vivo and in vitro. METHODS: Peritoneal
      macrophages from C57BL/6J mice treated orally with the EA extract of TWHF were
      assayed for NO production and iNOS messenger RNA (mRNA) expression by reverse
      transcriptase-polymerase chain reaction. The murine fibroblast cell line NIH3T3
      was also assessed for NO production and iNOS mRNA expression, as well as for iNOS
      promoter activation, Oct-1 nuclear binding capacity, and Oct-1 protein content by
      transient transfection, electrophoretic mobility shift assay, and immunoblotting,
      respectively. RESULTS: NO production and iNOS mRNA expression by macrophages from
      C57BL/6J mice immunized with trinitrophenyl-bovine serum albumin in Freund's
      complete adjuvant were significantly inhibited by oral administration of the EA
      extract (52.3% and 59.8% of control, respectively, at one-eighth of the dose that
      is lethal for 50% of the animals [LD(50)] and 21.0% and 38.1% of control,
      respectively, at one-fourth the LD(50)). Moreover, the EA extract and triptolide
      significantly inhibited NO production in vitro in activated peritoneal
      macrophages, which reflected a decreased level of iNOS mRNA. Finally, triptolide
      inhibited promoter activity of the iNOS gene and induction of the activity of the
      regulator of iNOS transcription, Oct-1. CONCLUSION: The EA extract of TWHF and
      triptolide inhibit transcription of the iNOS gene. This may contribute to the
      antiinflammatory effects of this traditional herbal remedy.

PMID- 15457470
TI  - Efficacy of modified recombinant type II collagen in modulating autoimmune
      arthritis.
AB  - OBJECTIVE: Previous studies have shown that an analog peptide of the
      immunodominant T cell determinant of type II collagen (CII), i.e., CII(256
      276)(N(263), D(266)), was able to suppress the immune response to CII and the
      development of arthritis in DR1-transgenic mice. The present study tested the
      hypothesis that introduction of the same amino acid substitutions into full
      length CII might improve the efficacy of the mutant collagen in achieving
      suppression of autoimmune arthritis. METHODS: Using recombinant technology, full
      length CII was modified, while the native conformation was retained. Two point
      mutations were introduced within the immunodominant T cell determinant to convert
      the F(263) to N and E(266) to D, using a baculovirus expression system that has
      previously been utilized in the production of recombinant CII (rCII). RESULTS:
      The mutant rCII(N(263), D(266)) was capable of reducing the incidence and
      severity of arthritis as well as the antibody response to CII when administered
      to DR1-transgenic mice that display susceptibility to collagen-induced arthritis.
      More importantly, it was significantly more effective than the synthetic analog
      peptide, CII(256-276)(N(263), D(266)). Its mechanism of suppression may be
      explained by the secretion of predominantly Th2 cytokines by the T cells
      immunized with rCII(N(263), D(266)). Administration of rCII(N(263), D(266)) was
      ineffective in suppressing arthritis in IL4(-/-) mice, suggesting that the
      profound suppressive effects of rCII(N(263), D(266)) were mediated through the
      production of interleukin-4. CONCLUSION: These findings describe a promising
      specific immunotherapy for patients with DR1-mediated autoimmunity to CII.

PMID- 15457471
TI  - Enhanced neutrophil extravasation and rapid progression of proteoglycan-induced
      arthritis in TSG-6-knockout mice.
AB  - OBJECTIVE: To gain insight into the mechanisms of the antiinflammatory effect of
      tumor necrosis factor alpha (TNFalpha)-induced protein 6 (Tnfip6) in arthritis,
      using Tnfip6-deficient animals. METHODS: TNFalpha-stimulated gene 6 (TSG-6)
      coding for Tnfip6 was disrupted. Tnfip6-deficient mice were backcrossed into
      proteoglycan-induced arthritis (PGIA)-susceptible BALB/c mice, and arthritis was
      induced by systemic immunization with cartilage proteoglycan (PG). Thioglycollate
      induced sterile peritonitis was also assessed, to monitor the early events of
      neutrophil extravasation in wild-type and Tnfip6-deficient mice in the presence
      or absence of treatment with recombinant murine Tnfip6. RESULTS: The onset of
      PGIA was similar, but progression and severity were significantly greater, in
      Tnfip6-deficient mice compared with wild-type BALB/c mice. However, this was not
      associated with enhanced T or B cell responses to cartilage PGs, but rather, an
      early and more extensive infiltration of the synovium with neutrophil leukocytes
      was the most prominent histopathologic feature of PGIA in Tnfip6-deficient mice.
      This was accompanied by elevated serum levels of interleukin-6 and amyloid A, and
      significantly increased activities of the enzymes plasmin, myeloperoxidase, and
      neutrophil elastase in the inflamed paw joints of Tnfip6-null mice, when compared
      with that of the wild-type littermates. Loss of control over several components
      of inflammation resulted in extensive and rapid cartilage degradation, bone
      erosion, joint ankylosis, and deformities in Tnfip6-null animals. In support of
      the antiinflammatory effect of Tnfip6 via the inhibition of polymorphonuclear
      (PMN) cell efflux, neutrophil invasion during thioglycollate-induced peritonitis
      was 2-fold higher in Tnfip6-deficient animals than in wild-type animals, but was
      dramatically suppressed by intravenous injection of recombinant murine Tnfip6.
      CONCLUSION: Tnfip6 is a multifunctional antiinflammatory protein that is produced
      at the site of inflammation and can be retained by the hyaluronan-rich
      extracellular matrix. A major effect of Tnfip6 is the inhibition of the
      extravasation of PMN cells, predominantly neutrophils, into the site of
      inflammation, most likely via a CD44/hyaluronan/Tnfip6-mediated blocking
      mechanism.

PMID- 15457472
TI  - Reduced leukocyte-endothelial cell interactions in the inflamed microcirculation
      of macrophage migration inhibitory factor-deficient mice.
AB  - OBJECTIVE: Macrophage migration inhibitory factor (MIF) is a proinflammatory
      cytokine with established roles in a range of inflammatory conditions. However,
      it is not known whether MIF influences inflammation via the direct promotion of
      leukocyte-endothelial cell interactions. Therefore, the aim of these experiments
      was to investigate the ability of MIF to regulate leukocyte-endothelial cell
      interactions in the inflamed microvasculature. METHODS: Intravital microscopy was
      used to examine postcapillary venules in the cremaster muscle and synovium of
      wild-type and MIF(-/-) mice. Leukocyte-endothelial cell interactions (rolling,
      adhesion, emigration) were compared under a range of inflammatory conditions.
      RESULTS: In cremasteric postcapillary venules of MIF(-/-) mice,
      lipopolysaccharide (LPS)-induced leukocyte rolling, adhesion, and emigration were
      significantly reduced relative to that in wild-type mice. Similar responses were
      observed in response to tumor necrosis factor alpha and histamine. Examination of
      the synovial microvasculature following exposure to carrageenan revealed that
      leukocyte rolling and adhesion in synovial postcapillary venules and leukocyte
      entry into the joint space were also reduced significantly in MIF(-/-) mice. In
      each of these models, the level of P-selectin-dependent rolling was reduced in
      MIF(-/-) mice. Despite this, no difference in P-selectin expression was observed
      following LPS treatment. However, microvascular shear forces were elevated in
      MIF(-/-) mice, raising a possible mechanism to explain the reduced interactions
      in these animals. CONCLUSION: MIF(-/-) mice consistently displayed a reduction in
      P-selectin-dependent rolling, suggesting that MIF exerts proinflammatory effects,
      in part, via the promotion of P-selectin-mediated rolling. Together, these data
      indicate that MIF promotes interactions between leukocytes and endothelial cells,
      thereby enhancing the entry of leukocytes into sites of inflammation.

PMID- 15457473
TI  - Deletion of the gene encoding CD59a in mice increases disease severity in a
      murine model of rheumatoid arthritis.
AB  - OBJECTIVE: To investigate the roles of CD59a in the protection of joint tissue in
      the context of murine antigen-induced arthritis (AIA). METHODS: AIA was triggered
      in CD59a-deficient (CD59a(-/-)) mice and in CD59a-sufficient (CD59a(+/+))
      controls; the course and severity of disease were compared between groups. The
      effects on arthritis of restoring CD59 to the joint in CD59a(-/-) mice by use of
      a membrane-targeted recombinant CD59 were also explored. RESULTS: Disease, as
      assessed clinically by measurement of joint swelling on day 1 (P < 0.0001), day 2
      (P < 0.01), and day 7 (P < 0.02) and histologically from indicators of joint
      damage on day 21 (P < 0.02), was significantly enhanced in CD59a(-/-) mice
      compared with CD59a(+/+) wild-type controls. Membrane attack complex (MAC)
      deposition in the arthritic joints of CD59a(-/-) mice was also increased compared
      with that in the joints of CD59a(+/+) controls. Restitution of CD59 activity in
      joints of CD59a(-/-) mice was attempted with soluble recombinant rat CD59 (sCD59)
      or with a novel membrane-targeted rat CD59 derivative (sCD59-APT542). Strong
      immunohistochemical staining of the synovial membrane and subsynovial tissue was
      apparent in sCD59-APT542-injected joints, but not in joints injected with
      untargeted sCD59. Intraarticular administration of sCD59-APT542 markedly
      ameliorated disease severity in CD59a(-/-) mice, knee swelling was significantly
      reduced over the time course of the disease, and joint damage, assessed
      histologically, was significantly milder on day 21 (P < 0.05). CONCLUSION: These
      data firmly implicate the MAC of complement as a major effector of joint damage
      in the murine AIA model of rheumatoid arthritis (RA), and they provide a
      rationale for the inhibition of MAC assembly as a therapeutic strategy for RA.

PMID- 15457474
TI  - Use of sunscreens to protect against ultraviolet-induced lupus erythematosus.

PMID- 15457475
TI  - Lack of linkage of IL1RN genotypes with ankylosing spondylitis susceptibility.

PMID- 15457476
TI  - Disseminated Salmonella typhimurium infection secondary to infliximab treatment.

PMID- 15457477
TI  - Results of anakinra treatment in rheumatoid arthritis patients previously treated
      with tumor necrosis factor alpha blockade: comment on the article by Buch et al.

PMID- 15457479
TI  - Failure to report previously used drugs and dosages in pharmaceutical company
      sponsored rheumatoid arthritis trials: comment on the article by Yocum et al.

PMID- 15457481
TI  - Radiographic progression in early rheumatoid arthritis: comment on the article by
      Goronzy et al.

PMID- 15457483
TI  - Ultrasonography of the shoulder in patients with rheumatoid arthritis: comment on
      the article by Hermann et al.

PMID- 15457485
TI  - Electroretinograms of children born to mothers treated with hydroxychloroquine
      during pregnancy and breast-feeding: comment on the article by Costedoat
      Chalumeau et al.

PMID- 15457487
TI  - Elective pregnancy termination and microchimerism: comment on the article by
      Khosrotehrani et al.

PMID- 15457489
TI  - Causes of familial aggregation of fibromyalgia: comment on the article by Arnold
      et al.

PMID- 15457492
TI  - An active insect kinin analog with 4-aminopyroglutamate, a novel cis-peptide
      bond, type VI beta-turn motif.
AB  - The insect kinins are potent diuretic peptides that preferentially form a cis
      Pro, type VI beta-turn. An insect kinin analog containing (2S,4S)-4
      aminopyroglutamate, a novel cis-peptide bond, type VI beta-turn motif,
      demonstrates significant activity in the physiological range in a cricket
      diuretic assay. This is the first instance of a 4-aminopyroglutamate analog of a
      peptide with a preference for a type VI turn that demonstrates significant
      bioactivity. The results provide further confirmatory evidence for the active
      conformation of the insect kinins, and a new scaffold with which to design
      biostable, peptidomimetic analogs capable of disrupting critical insect kinin
      regulated processes in insects.

PMID- 15457494
TI  - When and how do diaminocarbenes dimerize?
AB  - No example of a simple uncatalyzed dimerization of a diaminocarbene has been
      clearly established, so it is timely to ask what factors control the
      thermodynamics of this reaction, and what mechanisms are responsible for the
      observed dimerizations? In agreement with qualitative experimental observations,
      the dimerizations of simple five- and six-membered-ring diaminocarbenes are
      calculated to be 100 kJ mol(-1) less favorable than those of acyclic
      counterparts. This large difference is semiquantitatively accounted for by bond
      and torsional angle changes around the carbene centers. Carbenes such as
      (Et(2)N)(2)C are kinetically stable in THF at 25 degrees C in agreement with
      calculated energy barriers, but they rapidly dimerize in the presence of the
      corresponding formamidinium ion. This proton-catalyzed process is probably the
      most common mechanism for dimer formation, and involves formation of C-protonated
      dimers, which can be observed in suitable cases. The possibility of alkali-metal
      promoted dimerization is raised, and circumstantial evidence for this is
      presented.

PMID- 15457496
TI  - Comparative analysis of the conformational profile of substance P using simulated
      annealing and molecular dynamics.
AB  - The present study describes an extensive conformational search of substance P
      using two different computational methods. On the one hand, the peptide was
      studied using the iterative simulated annealing, and on the other, molecular
      dynamics simulations at 300 and 400 K. With the former method, the peptide was
      studied in vacuo with a dielectric constant of 80, whereas using the latter study
      the peptide was studied in a box of TIP3P water molecules. Analysis of the
      results obtained using both methodologies was carried out using an in-house
      methodology using a cluster analysis method based on information theory.
      Comparison of the two sampling methodologies and the different environment used
      in the calculations is also analyzed. Finally, the conformational motifs that are
      characteristic of substance P in a hydrophilic environment are presented and
      compared with the experimental results available in the literature.

PMID- 15457497
TI  - Relationship of MAO-A promoter (u-VNTR) and COMT (V158M) gene polymorphisms to
      CSF monoamine metabolites levels in a psychiatric sample of caucasians: A
      preliminary report.
AB  - Monoamine oxidase A gene promoter (MAOA-uVNTR) and catechol-O-methyltransferase
      V158M (COMT-V158M) gene functional polymorphisms are reported to be associated
      with impulsive-aggression, but a biological intermediate effect remains to be
      determined. This study assessed the association of these polymorphisms with
      cerebrospinal fluid (CSF) monoamine metabolites as endophenotypes. Ninety-eight
      Caucasian psychiatric subjects were assessed for Axis I and II diagnosis.
      Subjects were genotyped for the functional polymorphisms, MAOA-uVNTR and COMT
      V158M. CSF was obtained by lumbar puncture. Relationships of the two polymorphism
      to monoamine metabolites: HVA, 5-HIAA, and MHPG were examined. The higher
      expressing MAOA-uVNTR genotype was associated with higher CSF-HVA levels in males
      only (n = 46) (195.80 pmol/ml, SD = 61.64 vs. 161.13, SD = 50.23, respectively; P
      = 0.042). No association was found with diagnosis. COMT-V158M had no association
      with CSF monoamine metabolites. The association of MAOA-uVNTR with dopaminergic
      activity in males is a preliminary finding that needs to be replicated in a
      larger sample of Caucasian males and relationships sought with clinical
      phenotypes. This article contains supplementary material, which may be viewed at
      the American Journal of Medical Genetics website at
      http://www.interscience.wiley.com/jpages/0148-7299:1/suppmat/index.html.

PMID- 15457498
TI  - Mutation screen of the brain derived neurotrophic factor gene (BDNF):
      identification of several genetic variants and association studies in patients
      with obesity, eating disorders, and attention-deficit/hyperactivity disorder.
AB  - Several lines of evidence indicate an involvement of brain derived neurotrophic
      factor (BDNF) in body weight regulation and activity: heterozygous Bdnf knockout
      mice (Bdnf(+/-)) are hyperphagic, obese, and hyperactive; furthermore, central
      infusion of BDNF leads to severe, dose-dependent appetite suppression and weight
      loss in rats. We searched for the role of BDNF variants in obesity, eating
      disorders, and attention-deficit/hyperactivity disorder (ADHD). A mutation screen
      (SSCP and DHPLC) of the translated region of BDNF in 183 extremely obese children
      and adolescents and 187 underweight students was performed. Additionally, we
      genotyped two common polymorphisms (rs6265: p.V66M; c.-46C > T) in 118 patients
      with anorexia nervosa, 80 patients with bulimia nervosa, 88 patients with ADHD,
      and 96 normal weight controls. Three rare variants (c.5C > T: p.T2I; c.273G > A;
      c.*137A > G) and the known polymorphism (p.V66M) were identified. A role of the
      I2 allele in the etiology of obesity cannot be excluded. We found no association
      between p.V66M or the additionally genotyped variant c.-46C > T and obesity, ADHD
      or eating disorders. This article contains supplementary material, which may be
      viewed at the American Journal of Medical Genetics website at
      http://www.interscience.wiley.com/jpages/0148-7299:1/suppmat/index.html.

PMID- 15457499
TI  - Identification of a novel 45 repeat unstable allele associated with a disease
      phenotype at the MJD1/SCA3 locus.
AB  - We report a three generation Indian pedigree with the proband having 45 repeats
      at the Machado Joseph Disease (MJD)/spinocerebellar ataxia 3 (SCA3) disease
      locus. The proband exhibited clinical features of SCA and showed signs of
      cerebellar and brainstem atrophy on the MRI scan. The 45 repeat allele was
      unstable upon inter-generational transmission and was associated with a haplotype
      found in the majority of MJD/SCA3 patients from around the world. This is the
      smallest unstable allele reported till date at the MJD/SCA3 locus and may greatly
      reduce the gap between normal and pathological repeat ranges. This article
      contains supplementary material, which may be viewed at the American Journal of
      Medical Genetics website at http://www.interscience.wiley.com/jpages/0148
      7299:1/suppmat/index.html.

PMID- 15457501
TI  - Relationship between dopaminergic neurotransmission, alcoholism, and Reward
      Deficiency syndrome.
AB  - In this review, we described the neural substrates underlying Reward Deficiency
      syndrome which, in turn, is posited to underlie alcohol dependency. Alcoholism is
      a complex, multifactorial disorder that results from the interplay between
      genetic and environmental factors. The D(2) dopamine receptor (DRD(2)) has been
      associated with pleasure, and the DRD(2) A1 allele has been referred to as a
      reward gene. Evidence suggests that there is a tripartite interaction involving
      dopamine receptor deficiency, a propensity to abuse alcohol, and reduced
      sensitivity to rewards. This interaction relies heavily on genetic
      characteristics of the individual, with certain ethnic groups having a greater
      tendency toward alcoholism than others. The DRD(2) has been one of the most
      widely studied in neuropsychiatric disorders in general, and in alcoholism and
      other addictions in particular. The dopamine D2 (DRD2) gene, and especially its
      allele TaqI A1 allele and its receptor, also may be involved in comorbid
      antisocial personality disorder symptoms, high novelty seeking, and related
      traits. The mesocorticolimbic dopaminergic pathway system plays an especially
      important role in mediating reinforcement by abused drugs, and it may be a common
      denominator for addictions such as alcoholism. When the mesocorticolimbic
      dopamine reward system dysfunctions (perhaps caused by certain genetic variants),
      the end result is Reward Deficiency syndrome and subsequent drug-seeking
      behaviors. Reward Deficiency syndrome refers to the breakdown of the reward
      cascade, and resultant aberrant conduct, due to genetic and environmental
      influences. Alcohol and other drugs of abuse, as well as most positive
      reinforcers, cause activation and neuronal release of brain dopamine, which can
      decrease negative feelings and satisfy abnormal cravings. A deficiency or absence
      of DRD(2) receptors then predisposes individuals to a high risk for multiple
      addictive, impulsive, and compulsive behaviors. Although other neurotransmitters
      (e.g., glutamate, gamma-aminobutyric acid (GABA), and serotonin) may be important
      in determining the rewarding and stimulating effects of ethanol, dopamine may be
      critical for initiating drug use and for reinstating drug use during protracted
      abstinence. This article contains supplementary material, which may be viewed at
      the American Journal of Medical Genetics website at
      http://www.interscience.wiley.com/jpages/0148-7299:1/suppmat/index.html.

PMID- 15457502
TI  - GABAergic and glycinergic presympathetic neurons of rat medulla oblongata
      identified by retrograde transport of pseudorabies virus and in situ
      hybridization.
AB  - Electron microscopy suggests that up to half the synaptic input to sympathetic
      preganglionic neurons (SPGNs) is GABAergic or glycinergic. A proportion of this
      input is suspected to originate from neurons located within the medulla
      oblongata. The present study provides definitive evidence for the existence of
      these supraspinal presympathetic (PS) neurons with inhibitory phenotypes. PS
      neurons were identified by retrograde trans-synaptic migration of pseudorabies
      virus (PRV) injected into the adrenal gland. GABAergic or glycinergic cell bodies
      were identified by the presence of glutamate decarboxylase (GAD)-67 mRNA or
      glycine transporter (GlyT)-2 mRNA detected with in situ hybridization (ISH).
      Neither GABAergic nor glycinergic PS neurons were tyrosine hydroxylase (TH)
      immunoreactive (ir). GABAergic PS neurons were located within the ventral
      gigantocellular nucleus, gigantocellular nucleus alpha, and medial reticular
      formation, mostly medial to the TH-ir PS neurons. About 30% of GABAergic PS
      neurons were serotonergic cells located in the raphe pallidus (RPa) and
      parapyramidal region (PPyr). Glycinergic PS neurons had the same general
      distribution as the GABAergic cells, except that no glycinergic neurons were
      located in the RPa or PPyr and none were serotonergic. PRV immunohistochemistry
      combined with ISH for both GlyT2 and GAD-67 mRNAs showed that at least 63% of
      midline medulla GABAergic PS neurons were also glycinergic and 76% of glycinergic
      PS neurons were GABAergic. In conclusion, the rostral ventromedial medulla
      contains large numbers of GABAergic and glycinergic neurons that innervate
      adrenal gland SPGNs. Over half of these PS neurons may release both transmitters.
      The physiological role of this medullary inhibitory input remains to be explored.

PMID- 15457503
TI  - Time course of embryonic midbrain and thalamic auditory connection development in
      mice as revealed by carbocyanine dye tracing.
AB  - Central auditory connections develop in mice before the onset of hearing, around
      postnatal day 7. Two previous studies have investigated the development of
      auditory nuclei projections and lateral lemniscal nuclear projections in
      embryonic rats, respectively. Here, we provide detail for the first time of the
      initiation and progression of projections from the inferior colliculus (IC) to
      the medial geniculate body (MGB) and from the MGB to the auditory cortex (AC).
      Overall, the developmental progression of projections follows that of terminal
      mitoses in various nuclei, suggesting the consistent use of a developmental
      timetable at a given nucleus, independent of that of other nuclei. Our data
      further suggest that neurons project specifically and reciprocally from the MGB
      to the AC as early as embryonic day 14.5. These projections develop approximately
      a day before the reciprocal connections between the MGB and IC and before
      development of projections from the auditory nuclei to the IC. The development of
      IC projections is prolonged and progresses from rostral to caudal areas.
      Brainstem nuclear projections to the IC arrive first from the lateral lemniscus
      nuclei then the superior olive and finally the cochlear nuclei. Overall, the
      auditory connection development strongly suggests that most of the overall
      specificity of nuclear connections is set up at least 2 weeks before the onset of
      sound-mediated cochlea responses in mice and, thus, is likely governed
      predominantly by molecular genetic clues.

PMID- 15457504
TI  - Immunohistochemical distribution of tachykinins in the CNS of the lamprey
      Petromyzon marinus.
AB  - The presence of tachykinins in the CNS of vertebrates has been known for many
      decades, and numerous studies have described their distribution in mammals.
      Tachykinins were also reported in the CNS of lampreys using immunohistochemistry,
      chromatography, and radioimmunoassay methods, but the use of substance P (SP)
      specific antibodies to reveal those tachykinins could have led to an
      underestimation of their number in this genus. Therefore, we carried out a new
      immunohistochemical study on Petromyzon marinus using a commercial polyclonal
      antibody that binds not only to mammalian SP, but also to other neurokinins. This
      antibody labeled all previously described lamprey tachykinin-containing neuronal
      populations, but more important, labeled new populations in several parts of the
      brain. These include the dorsal gray of the rostral spinal cord, the dorsal
      column nuclei, the octavolateral area, the nucleus of the solitary tract, the
      medial rhombencephalic reticular formation, the lateral tegmentum of the rostral
      rhombencephalon, the torus semicircularis, the optic tectum, the habenula, the
      mammillary area, the dorsal thalamic area, the lateral hypothalamus, and the
      septum area. Preabsorption experiments confirmed the binding of the antibody to
      neurokinins and allowed us to propose that the CNS of P. marinus contains at
      least two different tachykinins.

PMID- 15457505
TI  - Colocalization of urocortin and neuronal nitric oxide synthase in the
      hypothalamus and Edinger-Westphal nucleus of the rat.
AB  - Different lines of studies suggest that both the corticotropin-releasing hormone
      related peptide Urocortin I (Ucn) and the neuromodulator nitric oxide (NO) are
      involved in the regulation of the complex mechanisms controlling feeding and
      anxiety-related behaviors. The aim of the present study was to investigate the
      possible interaction between Ucn and NO in the hypothalamic paraventricular
      nucleus (PVN), an area known to be involved in the modulation of these particular
      behaviors. Therefore, we mapped local mRNA and peptide/protein presence of both
      Ucn and the NO producing neuronal NO synthase (nNOS). This investigation was
      extended to include the hypothalamic supraoptic nucleus (SON) and the Edinger
      Westphal nucleus area (EW), the latter being one of the major cellular Ucn
      expressing sites. Furthermore, we compared the two predominantly used laboratory
      rat strains, Wistar and Sprague-Dawley. Ucn mRNA and immunoreactivity were
      detected in the SON and in the EW. A significant difference between Wistar and
      Sprague-Dawley rats was found in mRNA levels in the EW. nNOS was detected in all
      brain areas analyzed, showing a significantly lower immunoreactivity in the PVN
      and EW of Sprague-Dawley versus Wistar rats. Contrary to some previous reports,
      no Ucn mRNA and only a very low immunoreactivity were detectable in the PVN of
      either rat strain. Interestingly, double-labeling immunofluorescence revealed
      that in the SON approximately 75% of all cells immunoreactive for Ucn were
      colocalized with nNOS, whereas in the EW only approximately 2% of the Ucn neurons
      were found to contain nNOS. These findings suggest an interaction between Ucn and
      NO signaling within the SON, rather than the PVN, that may modulate the
      regulation of feeding, reproduction, and anxiety-related behaviors.

PMID- 15457506
TI  - Amygdalostriatal projections in reptiles: a tract-tracing study in the lizard
      Podarcis hispanica.
AB  - Whereas the lacertilian anterior dorsal ventricular ridge contains unimodal
      sensory areas, its posterior part (PDVR) is an associative center that projects
      to the hypothalamus, thus being comparable to the amygdaloid formation. To
      further understand the organization of the reptilian cerebral hemispheres, we
      have used anterograde and retrograde tracing techniques to study the projections
      from the PDVR and adjoining areas (dorsolateral amygdala, DLA; deep lateral
      cortex, dLC; nucleus sphericus, NS) to the striatum in the lizard Podarcis
      hispanica. This information is complemented with a detailed description of the
      organization of the basal telencephalon of Podarcis. The caudal aspect of the
      dorsal ventricular ridge projects nontopographically mainly (but not exclusively)
      to the ventral striatum. The NS projects bilaterally (with strong ipsilateral
      dominance) to the nucleus accumbens, thus recalling the posteromedial cortical
      amygdala of mammals. The PDVR (especially its lateral aspect) and the dLC project
      massively to a continuum of structures connecting the striatoamygdaloid
      transition area (SAT) and the nucleus accumbens (rostrally), the projection
      arising from the dLC being probably bilateral. Finally, the DLA projects
      massively and bilaterally to both the ventral and dorsal striatum, including the
      SAT. Our findings lend further support to the view that the PDVR and neighboring
      structures constitute the reptilian basolateral amygdala and indicate that an
      emotional brain was already present in the ancestral amniote. These results are
      important to understand the comparative significance of the caudal aspect of the
      amniote cerebral hemispheres, and specifically challenge current views on the
      nature of the avian caudal neostriatum.

PMID- 15457507
TI  - Laminar organization of the developing lateral olfactory tract revealed by
      differential expression of cell recognition molecules.
AB  - The projection neurons in the olfactory bulb (mitral and tufted cells) send axons
      through the lateral olfactory tract (LOT) onto several structures of the
      olfactory cortex. However, little is known of the molecular and cellular
      mechanisms underlying establishment of functional connectivity from the bulb to
      the cortex. Here, we investigated the developmental process of LOT formation by
      observing expression patterns of cell recognition molecules in embryonic mice. We
      immunohistochemically identified a dozen molecules expressed in the developing
      LOT and some of them were localized to subsets of mitral cell axons.
      Combinatorial immunostaining for these molecules revealed that the developing LOT
      consists of three laminas: superficial, middle, and deep. Detailed
      immunohistochemical, in situ hybridization, and 5-bromodeoxyuridine labeling
      analyses suggested that the laminar organization reflects: 1) the segregated
      pathways from the accessory and main olfactory bulbs, and 2) the different
      maturity of mitral cell axons. Mitral cell axons of the accessory olfactory bulb
      were localized to the deep lamina, segregated from those of the main olfactory
      bulb. In the main olfactory pathway, axons of mature mitral cells, whose somata
      is located in the apical sublayer of the mitral cell layer, were localized to the
      middle lamina within LOT, while those of immature mitral cells that located in
      the basal sublayer were complementarily localized to the superficial lamina.
      These results suggest that newly generated immature axons are added to the most
      superficial lamina of LOT successively, leading to the formation of piled laminas
      with different maturational stages of the mitral cell axons.

PMID- 15457508
TI  - Tcf binding sequence and position determines beta-catenin and Lef-1
      responsiveness of MMP-7 promoters.
AB  - The matrix metalloproteinase-7 (MMP-7) gene is a target of beta-catenin
      transactivation. Expression of the T-cell factor, Lef-1, enhances transcriptional
      activation of the human MMP-7 promoter by beta-catenin, but represses activation
      of the mouse MMP-7 promoter, both activities through consensus Tcf binding sites.
      The mouse promoter has a single Tcf binding element (mTBE) located downstream of
      the transcriptional start site, while the human promoter has two Tcf binding
      elements (hTBE1, hTBE2), both located upstream of the transcriptional start.
      hTBE1 and hTBE2 also differ in sequence from mTBE. Here we demonstrate that
      positioning of mTBE, upstream or downstream of the transcriptional start site
      dictated whether Lef-1 functioned as an activator or repressor, respectively.
      Sequence differences between mTBE and hTBE sites determined the potency of these
      activities, with hTBE sites being weaker. Mutational analysis of mTBE showed that
      increased Lef-1 activity mapped to G . C base pairings at 5' and 3' ends, and
      correlated with a threefold increase in Lef-1 binding affinity in vitro.
      Heterologous promoters with high affinity binding sites were 115-fold more
      responsive to beta-catenin than those with low affinity sites. Converting low
      affinity Tcf binding sites to high affinity sites increased beta-catenin
      responsiveness of the mouse and human promoters by 2-3 fold, and ectopic
      expression of Lef-1 increased beta-catenin responsiveness for promoters with low
      affinity binding sequences. We concluded that sequence and position of Tcf
      binding sites can determine the extent of beta-catenin-Lef-1 responsiveness for
      beta-catenin target genes.

PMID- 15457510
TI  - Thermal effects and vibrational corrections to transition metal NMR chemical
      shifts.
AB  - Both zero-point and classical thermal effects on the chemical shift of transition
      metals have been calculated at appropriate levels of density functional theory
      for a number of complexes of titanium, vanadium, manganese and iron. The zero
      point effects were computed by applying a perturbational approach, whereas
      classical thermal effects were probed by Car-Parrinello molecular dynamics
      simulations. The systematic investigation shows that both procedures lead to a
      deshielding of the magnetic shielding constants evaluated at the GIAO-B3 LYP
      level, which in general also leads to a downfield shift in the relative chemical
      shifts, delta. The effect is small for the titanium and vanadium complexes, where
      it is typically on the order of a few dozen ppm, and is larger for the manganese
      and iron complexes, where it can amount to several hundred ppm. Zero-point
      corrections are usually smaller than the classical thermal effect. The pronounced
      downfield shift is due to the sensitivity of the shielding of the metal centre
      with regard to the metal-ligand bond length, which increase upon vibrational
      averaging. Both applied methods improve the accuracy of the chemical shifts in
      some cases, but not in general.

PMID- 15457511
TI  - Benzene-templated hydrothermal synthesis of metal-organic frameworks with
      selective sorption properties.
AB  - In this paper, we report two metal-organic frameworks [Co3(ndc)3(bipyen)(1.5)]H2O
      (1) and [Co2(ndc)2bipyen)]C6H6.H2O (2) (bipyen=trans-1,2-bis(4-pyridyl)ethylene,
      H2ndc=2,6-naphthalenedicarboxylic acid). These compounds were both synthesized
      from identical hydrothermal reaction conditions except that benzene was added to
      the reaction for 2. Crystal structures show that the two compounds have triply
      interpenetrated three-dimensional frameworks and these frameworks have the same
      primary structure of a two-dimensional network of interconnected [Co2(O2CR)(4/2)]
      (R=naphthalene group) paddle-wheels and bridging bipyen ligands. Both compounds
      have guest water molecules and, in addition, 2 has guest benzene molecules.
      Structural transformations of the host accompanied guest removal, which can be
      monitored by powder X-ray diffraction. N2 adsorption data of 2 show that there
      are two different types of pores corresponding to the benzene and water pores.
      Upon exposure to vapors of several organic molecules, the heat-treated sample of
      2 adsorbs benzene and cyclohexene, but does not adsorb toluene, (o-, m-, and p
      )xylenes, cycloheptatriene, or cyclohexane.

PMID- 15457512
TI  - Protein synthesis and mRNA storage in cattle oocytes maintained under meiotic
      block by roscovitine inhibition of MPF activity.
AB  - Roscovitine, a specific inhibitor of MPF kinase activity, has been shown to block
      efficiently and reversibly the meiotic resumption of oocytes from different
      species, including cattle. In view to verify that oocytes maintain germinal
      vesicle like molecular activities under roscovitine treatment, we compared in the
      present study the M-phase Promoting Factor (MPF) and Mitogen Activated Protein
      (MAP) kinase activities; protein synthesis and phosphorylation patterns in
      oocytes and cumulus cells; and CDK1 and Cyclin B messengers storage under control
      culture and under roscovitine inhibition. We observed that roscovitine induced a
      full and reversible inhibition of MPF kinase activity and of the activating
      phosphorylation of both ERK1/2 MAPK. During in vivo maturation, there was a
      highly significant increase in the relative mRNA level of both cyclin B1 and CDK1
      whereas during in vitro culture, the relative amount of CDK1 messenger was
      reduced. These messengers may be used as markers for the optimization of in vitro
      maturation treatment. Roscovitine reversibly prevented this drop in relative
      quantities of CDK1 messenger. Oocytes cultured in the presence of roscovitine
      maintained a GV like profile of protein synthesis except that two proteins of 48
      and 64 kDa specific of matured oocytes also appeared under roscovitine treatment.
      However, roscovitine did not prevent most of the modifications of protein
      phosphorylation pattern observed during maturation. In conclusion, results of
      this study revealed that the use of roscovitine did not prevent all the events
      related to maturation of bovine oocytes.

PMID- 15457513
TI  - KIF2Abeta: A kinesin family member enriched in mouse male germ cells, interacts
      with translin associated factor-X (TRAX).
AB  - Translin associated factor X (TRAX) is a binding partner of TB-RBP/Translin. A
      cDNA encoding the 260 C-terminal amino acids of KIF2Abeta was isolated from mouse
      testis cDNAs in a yeast two-hybrid library screen for specific TRAX-interacting
      proteins. KIF2Abeta was expressed predominantly in the mouse testis and enriched
      in germ cells. The interaction of full-length KIF2Abeta or its C-terminus with
      TRAX was verified using in vitro synthesized fusion proteins. Deletion mapping of
      the TRAX-binding region of KIF2Abeta indicated that amino acids 514-659 were
      necessary and sufficient for the interaction in vivo. Confocal microscopy studies
      using GFP-fusion proteins demonstrated that KIF2Abeta colocalizes with TRAX in a
      perinuclear location. KIF2Abeta does not interact with TB-RBP, suggesting that
      either TRAX can function as an adaptor molecule for motor proteins and TB-RBP, or
      that this interaction reveals an undescribed role for TRAX in germ cells. The
      interaction with KIF2Abeta suggests a role for TRAX in microtubule-based
      functions during spermatogenesis.

PMID- 15457514
TI  - Polyol pathway along the bovine epididymis.
AB  - During the epididymal transit, male gametes acquire new surface proteins
      necessary for their fertilizing ability. We have previously shown that membranous
      vesicles, called epididymosomes, interact with sperm surface within the
      epididymal fluid allowing transfer of some proteins to different subcellular
      compartments of spermatozoa. We previously showed that one of the major proteins
      associated with epididymosomes was an aldose reductase (gene: AKR1B5) and
      confirmed that aldose reductase is located in the epithelial cells bordering the
      intraluminal compartment of the epididymis. The present study shows that
      cytosolic aldose reductase activity was maximal in the proximal and middle
      segments of the epididymis and decreased in the distal epididymis. Western and
      Northern blot analysis confirmed the distribution pattern of aldose reductase and
      of the encoding mRNA. The optimal pH of epididymal aldose reductase was 6.0-6.5
      when glucose was used as a substrate; this corresponds to the pH of the
      intraluminal epididymal fluid. In order to evaluate the possible involvement of
      sorbitol in sperm physiology, Western blot of tissue homogenates were probed with
      an anti-sorbitol dehydrogenase antibody. The amount of enzyme immunodetected was
      higher in the proximal and distal segments of the epididymis when compared to the
      amount detectable in the middle segment of the epididymis. Sorbitol dehydrogenase
      activity as well as the level of the encoding mRNA showed the same pattern of
      distribution. Furthermore, immunohistological studies using the anti-sorbitol
      dehydrogenase revealed that this enzyme was synthesized by the epididymal
      epithelial cells bordering the intraluminal compartment. Knowing the importance
      of sorbitol and fructose in sperm metabolism, we hypothesized that the polyol
      pathway is involved in the modulation of sperm motility within the epididymis.

PMID- 15457515
TI  - Expression pattern of the maternal factor zygote arrest 1 (Zar1) in bovine
      tissues, oocytes, and embryos.
AB  - Zygote arrest 1 (Zar1) is an ovary-specific maternal factor that plays an
      essential role during the oocyte-to-embryo transition in mouse. In this species,
      Zar1 expression is strictly limited to the oocyte, the zygote and, at a lower
      level, the 2-cell embryo. Aim of the present study was to analyze the presence
      and the expression pattern of the Zar1 ortholog in bovine tissues and embryos.
      Reverse transcription (RT)-polymerase chain reaction (PCR) analysis was performed
      in a panel of bovine tissues, in oocytes and pre-implantation in vitro produced
      embryos. The results demonstrated that a Zar1 ortholog is present in cattle. In
      the adult, the gene is expressed in ovary, testis, muscle, and myocardium. The
      gene is also expressed in the oocyte, the zygote, and in all the stages of
      embryonic development until blastocyst formation. A semi-quantitative RT-PCR
      analysis revealed that Zar1 levels are constant through in vitro development with
      the exception of the 4-cell stage, when a significant increase is observed. The
      exposure of fertilized oocytes to the RNA polymerase II inhibitor alpha-amanitin
      was able to suppress this Zar1 increase indicating that transcription of this
      gene occurs at the 4-cell stage. Zar1 is conserved in cattle but has an
      expression pattern different from the mouse. In particular, Zar1 expression in
      the adult is not limited to the ovary and in the embryo is expressed well beyond
      the oocyte to embryo transition. Moreover, the identification of Zar1
      transcription at the 4-cell stage represents the first characterization of one of
      the genes expressed in cattle embryos before the major onset of embryonic
      transcription.

PMID- 15457516
TI  - Chorionic gonadotropin regulates the transcript level of VHL, p53, and HIF-2alpha
      in human granulosa lutein cells.
AB  - The ovarian corpus luteum plays a critical role in reproduction being the primary
      source of circulating progesterone. After ovulation the corpus luteum is build by
      avascular granulosa lutein cells through rapid vascularization regulated by
      gonadotropic hormones. The present study was performed to investigate whether
      this process might be influenced by the human chorionic gonadotropin (hCG)
      dependent expression of different tumor suppressor genes and hypoxia dependent
      transcription factors. RNA was isolated from cultured granulosa lutein cells,
      transcribed into cDNA, and the transcript level of following genes were
      determined: RB-1, VHL, NF-1, NF-2, Wt-1, p53, APC, and hypoxia inducible factor-1
      (HIF-1), -2, and -3alpha. Additionally, the influence of hCG on the expression of
      VHL, p53, and HIf2alpha were investigated. We demonstrate that in human granulosa
      lutein cells the tumor suppressor genes RB-1, VHL, NF-1, NF-2, Wt-1, p53, and APC
      and the hypoxia dependent transcription factors HIF-1alpha, -2alpha, and -3alpha
      are expressed. In addition, we showed that hCG regulates the expression of p53,
      VHL, and HIF-2alpha. Our results indicate that hCG may determine the growth and
      development of the corpus luteum by mediating hypoxic and apoptotic pathways in
      human granulosa lutein cells.

PMID- 15457517
TI  - Species-related differences in blastocyst quality are associated with differences
      in relative mRNA transcription.
AB  - The objective of this study was to compare the relative transcript abundance of
      several important candidate genes between ovine and bovine blastocysts.
      Blastocysts were produced by in vitro maturation, fertilization, and subsequent
      culture in one of two formulations of synthetic oviduct fluid medium (SOF1 and
      SOF2). From each IVF replicate groups of 10 bovine and 10 ovine blastocysts from
      each of the two media were used for analysis of mRNA relative abundance.
      Transcript levels for mitochondrial Mn-superoxide dismutase (MnSOD), survivin,
      and glucose transport 5 (Glut-5) were significantly higher in ovine blastocysts
      than bovine (P < 0.05), while transcripts for Connexin 31 (Cx31), interferon tau
      (IFN-tau), and sarcosine oxidase (SOX) were significantly more abundant in bovine
      blastocysts (P < 0.01). For the two remaining transcripts, E-cadherin (E-cad) and
      Na/K ATPase (Na/K), there was no difference. Culture of bovine embryos in SOF2
      resulted in a significant increase in the level of expression of MnSOD and Glut-5
      (P < 0.05) compared to those bovine embryos cultured in SOF1. For all the other
      transcripts, except survivin, there was a significant decrease in the relative
      abundance. Culture of sheep embryos in either SOF1 or SOF2 did not have a major
      influence on transcript abundance; of the eight transcripts examined, the
      relative abundance of only one, SOX, was significantly altered. Bovine
      blastocysts produced in SOF2 had significantly higher survival rates at 24, 48,
      and 72 hr and significantly higher hatching rates following vitrification and
      warming than those cultured in SOF1 (P < 0.001). In conclusion, we have
      quantified for the first time the mRNA expression of a set of important
      developmental genes in sheep blastocysts and we have demonstrated that these
      differences between species in their adaptability to culture conditions,
      manifested in differences in embryo morphology and cryotolerance, are related to
      differences in mRNA relative abundance. The results also highlight the usefulness
      of transcript analysis as a marker of embryo quality.

PMID- 15457518
TI  - Immunolocalization of bovine sperm protease BSp120 by light and electron
      microscopy during capacitation and the acrosome reaction: its role in in vitro
      fertilization.
AB  - Mammalian fertilization involves various steps in which the participation of
      specific enzymes has been demonstrated by numerous studies. Acrosin is one of the
      most widely acrosomal protease in mammalian spermatozoa studied, including
      bovine; however, other proteases have also been described. A new trypsin-like
      serine protease named bovine serine protease of 120 kDa (BSp120) and its pre
      cursor BSp66 (66 kDa) were identified in bovine spermatozoa. Cytological and
      ultrastructural immunolocalization studies on BSp120 were performed in live and
      fixed cells. Immunoflorescence assays with specific polyclonal antibodies
      revealed localization of BSp120 on the sperm head, with a signal homogeneously
      distributed over the acrosome resembling a horseshoe. After the acrosome
      reaction, sperm showed a patchy pattern in the acrosomal cap. Immune electron
      microscopy analysis indicated that BSp120 is located over the head plasma
      membrane of capacitated spermatozoa and acrosome reacting spermatozoa. To assess
      BSp120 function in sperm-oocyte interaction, in vitro fertilization studies were
      conducted. Oocytes were incubated with spermatozoa pre-treated with anti-BSp120,
      anti-guinea pig acrosin, and anti-BSp120 plus anti-guinea pig acrosin. Pre
      treatment of bovine spermatozoa with antibodies towards each protein did not
      significantly modify fertilization rates. However, when both anti-acrosin and
      anti-BSp120 antibodies were simultaneously added, there was a significant
      decrease in the fertilization rate, suggesting that both enzymes may be required
      for fertilization. Altogether, the results from the present study described the
      localization of BSp120 over the acrosome of bovine sperm, and suggest its
      involvement in fertilization.

PMID- 15457519
TI  - Total synthesis of salicylihalamides A and B.
AB  - The paper illustrates two efficient routes to macrolactone 19 containing a 3
      (para-methoxybenzyloxy)propyl side chain at C-15. The chiral center at C-15 was
      introduced by a Noyori reduction of keto ester 5. The intermediate common to both
      routes, aldehyde 8, was prepared from keto ester 5. The subsequent chain
      extension utilized Evans aldol reactions. The first route leads to the alkene 14,
      which was used, after hydroboration, for a Suzuki cross-coupling reaction with
      vinyl iodide 15. The derived seco acid 18 was converted into the macrolactone 19
      by a Mitsunobu lactonization by using immobilized triphenylphosphine.
      Alternatively, an aldol reaction of 8 with the 4-pentenoyl derivative 20 was used
      to prepare alkene 26. This building block led to ester 28, which could also be
      converted into macrolactone 19 by the classical ring-closing metathesis. After
      conversion of the C-15 side chain to the corresponding aldehyde, the enamide was
      introduced through hemiaminal formation and formal elimination of water.
      Separation of the double-bond isomers and removal of the silyl protecting groups
      provided salicylihalamides A (E)-1 and B (Z)-1.

PMID- 15457520
TI  - Highly efficient and mild copper-catalyzed N- and C-arylations with aryl bromides
      and iodides.
AB  - Mild, efficient, copper-catalyzed N-arylation procedures for nitrogen
      heterocycles, amides, carbamates, and C-arylation procedures for malonic acid
      derivatives have been developed that afford high yields of arylated products with
      excellent selectivity. The N-arylation of imidazole with aryl bromides or iodides
      was found to be greatly accelerated by inexpensive, air-stable catalyst systems,
      combining catalytic copper salts or oxides with a set of structurally simple
      chelating ligands. The reaction was shown to be compatible with a broad range of
      aryl halides, encompassing sterically hindered, electron-poor, and electron-rich
      ones, providing the arylated products under particularly mild conditions (50-82
      degrees C). The lower limit in ligand and catalyst loading and the scope of
      Ullmann-type condensations catalyzed by complexes bearing those ligands with
      respect to the nucleophile class have also been investigated. Chelating Schiff
      base Chxn-Py-Al (1c) generates a remarkably general copper catalyst for N
      arylation of pyrrole, indole, 1,2,4-triazole, amides, and carbamates; and C
      arylation of diethyl malonate, ethyl cyanoacetate, and malononitrile with aryl
      iodides under mild conditions (50-82 degrees C). The new method reported here is
      the most successful to date with regard to Ullmann-type arylation of some of
      these nucleophiles.

PMID- 15457521
TI  - Cobalt-catalyzed cross-coupling reactions of alkyl halides with allylic and
      benzylic Grignard reagents and their application to tandem radical
      cyclization/cross-coupling reactions.
AB  - Details of cobalt-catalyzed cross-coupling reactions of alkyl halides with
      allylic Grignard reagents are disclosed. A combination of cobalt(II) chloride and
      1,2-bis(diphenylphosphino)ethane (DPPE) or 1,3-bis(diphenylphosphino)propane
      (DPPP) is suitable as a precatalyst and allows secondary and tertiary alkyl
      halides--as well as primary ones--to be employed as coupling partners for allyl
      Grignard reagents. The reaction offers a facile synthesis of quaternary carbon
      centers, which has practically never been possible with palladium, nickel, and
      copper catalysts. Benzyl, methallyl, and crotyl Grignard reagents can all couple
      with alkyl halides. The benzylation definitely requires DPPE or DPPP as a ligand.
      The reaction mechanism should include the generation of an alkyl radical from the
      parent alkyl halide. The mechanism can be interpreted in terms of a tandem
      radical cyclization/cross-coupling reaction. In addition, serendipitous tandem
      radical cyclization/cyclopropanation/carbonyl allylation of 5-alkoxy-6-halo-4-oxa
      1-hexene derivatives is also described. The intermediacy of a carbon-centered
      radical results in the loss of the original stereochemistry of the parent alkyl
      halides, creating the potential for asymmetric cross-coupling of racemic alkyl
      halides.

PMID- 15457522
TI  - EPR studies of amine radical cations, part 1: thermal and photoinduced
      rearrangements of n-alkylamine radical cations to their distonic forms in low
      temperature freon matrices.
AB  - The thermal and photochemical transformations of primary amine radical cations (n
      propyl 1.+, n-butyl 5.+) generated radiolytically in freon matrices have been
      investigated by using low-temperature EPR spectroscopy. Assignment of the spectra
      was facilitated by parallel studies on the corresponding N,N-dideuterioamines.
      The identifications were supported by quantum chemical calculations on the
      geometry, electronic structure, hyperfine splitting constants and energy levels
      of the observed transient radical species. The rapid generation of the primary
      species by a short exposure (1-2 min) to electron-beam irradiation at 77 K
      allowed the thermal rearrangement of 1.+ to be monitored kinetically as a first
      order reaction at 125-140 K by the growth in the well-resolved EPR signal of the
      distonic radical cation .C(2CH2CH2NH3+. By comparison, the formation of the
      corresponding .CH2CH2CH2CH2NH3+ species from 5.+ is considerably more facile and
      already occurs within the short irradiation time. These results directly verify
      the intramolecular hydrogen-atom migration from carbon to nitrogen in these
      ionised amines, a reaction previously proposed to account for the fragmentation
      patterns observed in the mass spectrometry of these amines. The greater ease of
      the thermal rearrangement of 5.+ is in accordance with calculations on the
      barrier heights for these intramolecular 1,5- and 1,4-hydrogen shifts, the lower
      barrier for the former being associated with minimisation of the ring strain in a
      six-membered transition state. For 1.+, the 1,4-hydrogen shift is also brought
      about directly at 77 K by exposure to approximately 350 nm light, although there
      is also evidence for the 1,3-hydrogen shift requiring a higher energy. A more
      surprising result is the photochemical formation of the H2C=N. radical as a minor
      product under hard-matrix conditions in which diffusion is minimal. It is
      suggested that this occurs as a consequence of the beta-fragmentation of 1.+ to
      the ethyl radical and the CH2=NH2+ ion, followed by consecutive cage reactions of
      deprotonation and hydrogen transfer from the iminonium group. Additionally,
      secondary ion-molecule reactions were studied in CFCl2CF2Cl under matrix
      conditions that allow diffusion. The propane-1-iminyl radical CH3CH2CH=N. was
      detected at high concentrations of the n-propylamine substrate. Its formation is
      attributed to a modified reaction sequence in which 1.+ first undergoes a proton
      transfer within a cluster of amine molecules to yield the aminyl radical
      CH3CH2CH2N.H. A subsequent disproportionation of these radicals can then yield
      the propane-1-imine precursor CH3CH2CH=NH, which is known to easily undergo
      hydrogen abstraction from the nitrogen atom. The corresponding butane-1-iminyl
      radical was also observed.

PMID- 15457525
TI  - Molecules as modulators: systems biology challenges chemistry.

PMID- 15457528
TI  - Preliminary studies on the in silico evolution of biochemical networks.
AB  - Due to the variety and importance of roles performed by signalling networks,
      understanding their function and evolution is of great interest. Signalling
      networks allow organisms to process and react to changes in their internal and
      external environment. Current estimates suggest that two to three percent of all
      genomes code for proteins involved in signalling networks. The study of
      signalling networks is hindered by the complexities of the networks and
      difficulties in ascribing function to form. For example, a very complex dense
      network might comprise eighty or more densely connected proteins. In the majority
      of cases there is very little understanding of how these networks process
      signals. Unlike in electronics, where there is a broad practical and theoretical
      understanding of how to construct devices that can process almost any kind of
      signal, in biological signalling networks there is no equivalent theory. Part of
      the problem stems from the fact that in most cases it is unknown what particular
      signal processing circuits would look like in a biological form. This paper
      describes the evolutionary methods used to generate networks with particular
      signal- and computational-processing capabilities. The techniques involved are
      described, and the approach is illustrated by evolving computational circuits
      such as multiplication, radicals and logarithmic functions. The experiments also
      illustrate the evolution of modularity within biochemical reaction networks.

PMID- 15457527
TI  - mRNA openers and closers: modulating AU-rich element-controlled mRNA stability by
      a molecular switch in mRNA secondary structure.
AB  - Approximately 3 000 genes are regulated in a time-, tissue-, and stimulus
      dependent manner by degradation or stabilization of their mRNAs. The process is
      mediated by interaction of AU-rich elements (AREs) in the mRNA's 3'-untranslated
      regions with trans-acting factors. AU-rich element-controlled genes of
      fundamentally different functional relevance depend for their activation on one
      positive regulator, HuR. Here we present a methodology to exploit this central
      regulatory process for specific manipulation of AU-rich element-controlled gene
      expression at the mRNA level. With a combination of single-molecule spectroscopy,
      computational biology, and molecular and cellular biochemistry, we show that mRNA
      recognition by HuR is dependent on the presentation of the sequence motif
      NNUUNNUUU in single-stranded conformation. The presentation of the HuR binding
      site in the mRNA secondary structure appears to act analogously to a regulatory
      on/off switch that specifically controls HuR access to mRNAs in cis. Based on
      this finding we present a methodology for manipulating ARE mRNA levels by
      actuating this conformational switch specifically in a target mRNA.
      Computationally designed oligonucleotides (openers) enhance the NNUUNNUUU
      accessibility by rearranging the mRNA conformation. Thereby they increase in
      vitro and endogenous HuR-mRNA complex formation which leads to specific mRNA
      stabilization (as demonstrated for TNFalpha and IL-2, respectively). Induced HuR
      binding both inside and outside the AU-rich element promotes functional IL-2 mRNA
      stabilization. This opener-induced mRNA stabilization mimics the endogenous IL-2
      response to CD28 stimulation in human primary T-cells. We therefore propose that
      controlled modulation of the AU-rich element conformation by mRNA openers or
      closers allows message stabilization or destabilization in cis to be specifically
      triggered. The described methodology might provide a means for studying distinct
      pathways in a complex cellular network at the node of mRNA stability control. It
      allows ARE gene expression to be potentially silenced or boosted. This will be of
      particular value for drug-target validation, allowing the diseased phenotype to
      ameliorate or deteriorate. Finally, the mRNA openers provide a rational starting
      point for target-specific mRNA stability assays to screen for low-molecular
      weight compounds acting as inhibitors or activators of an mRNA structure
      rearrangement.

PMID- 15457529
TI  - Systems biology and the molecular circuits of cancer.
AB  - Proliferative disorders are a major challenge for human health. The understanding
      of the organization of cell-cycle events is of the utmost importance to devise
      effective therapeutic strategies for cancer. The awareness that cells and
      organisms are complex, modular, hierarchical systems and the availability of
      genome-wide gene expression and protein analyses, should make it feasible to
      elucidate human diseases in terms of dysfunctions of molecular systems. Here we
      review evidence in support of a systems model of the cell cycle, in which two
      sequential growth-sensitive thresholds control entry into S-phase. The putative
      molecular determinants that set the threshold for entry into S-phase are
      consistently altered in cancer cells. Such a framework could be useful in guiding
      both experimental investigation and data analysis by allowing wiring to other
      relevant cell modules thereby highlighting the differential responses, or lack of
      response of cancer cells to intra- and extracellular factors. Pharmacological
      approaches that take advantage of transformation-induced fragility to glucose
      shortage are discussed. Extension of this hierarchical, modular approach to
      tumors as a whole holds promise for the development of effective drug discovery
      approaches and more efficient therapeutic protocols.

PMID- 15457530
TI  - Spatial and temporal sequence of events in cell adhesion: from molecular
      recognition to focal adhesion assembly.
AB  - A new concept that attributes a pivotal role to the pericellular coat in the
      regulation of the early stages of cell adhesion is presented. Quick, adaptable,
      and transient adhesion through multiple cooperative weak interactions provides
      the cell with an additional level of modulation in the decision-making process
      that precedes the commitment to adhesion at a particular site. Hyaluronan emerges
      as a modulator of cell adhesion in certain cells, mediating binding or repulsion
      through its polyelectrolyte character, in addition to its chirality and molecular
      recognition properties. The biophysical properties of hyaluronan as well as its
      ultrastructural organization are analyzed in relation to this proposed function.

PMID- 15457531
TI  - Directing flux in glycan biosynthetic pathways with a small molecule switch.

PMID- 15457532
TI  - NF-kappaB: a multifaceted transcription factor regulated at several levels.
AB  - NF-kappaB is a generic name for an evolutionarily conserved transcription-factor
      system that contributes to the mounting of an effective immune response but is
      also involved in the regulation of cell proliferation, development, and
      apoptosis. The implication of NF-kappaB in central biological processes and its
      extraordinary connectivity to other signaling pathways raise a need for highly
      controlled regulation of NF-kappaB activity at several levels. While all NF
      kappaB activation pathways share a central and critical proteasome-mediated step
      that leads to the degradation of inhibitory proteins and the release of DNA
      binding subunits, there is evidence for a downstream level of NF-kappaB
      regulation that employs several mechanisms. These include promoter-specific
      exchange of dimers and modification of the transactivating p65 subunit by
      phosphorylation, acetylation, ubiquitination, or prolyl isomerization. The
      signaling pathways and enzymes controlling this second level of regulation and
      their potential use as therapeutic targets for the treatment of NF-kappaB
      associated pathologies are discussed here.

PMID- 15457533
TI  - The systems biology of glycosylation.
AB  - Glycosylation can have a profound influence on the function of a variety of
      eukaryotic cells. In particular, it can affect signal transduction and cell-cell
      communication properties and thus shape critical cell decisions, including the
      regulation of differentiation and apoptosis. Regulation of glycosylation has
      multiple layers of complexity, both structural and functional, which make its
      experimental and theoretical analysis difficult to perform and interpret. Novel
      research methodologies provided by systems biology can help to address many
      outstanding issues and integrate glycosylation with other metabolic and cell
      regulation processes. Here we review the toolbox available for biochemical
      systems analysis of glycosylation.

PMID- 15457534
TI  - Synthesis of GTP-derived Ras ligands.
AB  - A practical and convenient method for the synthesis of acid- and base-sensitive
      GTP analogues carrying a further substituent at the terminal phosphate has been
      developed. Key to the successful synthesis of these potential ligands of the Ras
      protein is the use of Pd0-sensitive allyl protecting groups in a one-pot
      synthesis that avoids evaporation steps. Initial biochemical analysis of a
      representative compound revealed that such GTP analogues can bind to Ras and
      might open up the possibility of developing small molecules that can act as
      deactivators of oncogenic Ras.

PMID- 15457535
TI  - Computational design of reduced metabolic networks.
AB  - Cellular functions are based on thousands of chemical reactions and transport
      processes, most of them being catalysed and regulated by specific proteins.
      Systematic gene knockouts have provided evidence that this complex reaction
      network possesses considerable redundancy, that is, alternative routes exist
      along which signals and metabolic fluxes may be directed to accomplish an
      identical output behaviour. This property is of particular importance in cases
      where parts of the reaction network are transiently or permanently impaired, for
      example, due to an infection or genetic alterations. Here we present a
      computational concept to determine enzyme-reduced metabolic networks that are
      still sufficient to accomplish a given set of cellular functions. Our approach
      consists of defining an objective function that expresses the compromise that has
      to be made between successive reduction of the network by omission of enzymes and
      its decreasing thermodynamic and kinetic feasibility. Optimisation of this
      objective function results in a linear mixed-integer program. With increasing
      weight given to the reduction of the number of enzymes, the total flux in the
      network increases and some of the reactions have to proceed in thermodynamically
      unfavourable directions. The approach was applied to two metabolic schemes: the
      energy and redox metabolism of red blood cells and the carbon metabolism of
      Methylobacterium extorquens. For these two example networks, we determined
      various variants of reduced networks differing in the number and types of
      disabled enzymes and disconnected reactions. Using a comprehensive kinetic model
      of the erythrocyte metabolism, we assess the kinetic feasibility of enzyme
      reduced subnetworks. The number of enzymes predicted to be indispensable amounts
      to 14 (out of 28) for the erythrocyte scheme and 13 (out of 77) for the bacterium
      scheme, the largest group of enzymes predicted to be simultaneously dispensable
      amounts to 3 and 37 for these two systems. Our approach might contribute to
      identifying potential target enzymes for rational drug design, to rationalising
      gene-expression profiles of metabolic enzymes and to designing synthetic networks
      with highly specialised metabolic functions.

PMID- 15457536
TI  - A spectrum of models of signaling pathways.

PMID- 15457537
TI  - The concept of "buffering" in systems and control theory: from metaphor to math.
AB  - The paradigm of "buffering" is used increasingly for the description of diverse
      "systemic" phenomena encountered in evolutionary genetics, ecology, integrative
      physiology, and other areas. However, in this new context, the paradigm has not
      yet matured into a truly quantitative concept inasmuch as it lacks a
      corresponding quantitative measure of "systems-level buffering strength". Here, I
      develop such measures on the basis of a formal and general approach to the
      quantitation of buffering action. "Systems-level buffering" is shown to be
      synonymous with "disturbance rejection" in feedback-control systems, and can be
      quantitated by means of dimensionless proportions between partial flows in two
      partitioned systems. The units allow either the time-independent, "static"
      buffering properties or the time-dependent, "dynamic" ones to be measured.
      Analogous to this "resistance to change", one can define and measure the
      "conductance to change"; this quantity corresponds to "set-point tracking" in
      feedback-control systems. Together, these units provide a systematic framework
      for the quantitation of buffering action in systems biology, and reveal the
      common principle behind systems-level buffering, classical acid-base buffering,
      and multiple other manifestations of buffering.

PMID- 15457538
TI  - Tools for glycomics: mapping interactions of carbohydrates in biological systems.
AB  - The emerging field of glycomics has been challenged by difficulties associated
      with studying complex carbohydrates and glycoconjugates. Advances in the
      development of synthetic tools for glycobiology are poised to overcome some of
      these challenges and accelerate progress towards our understanding of the roles
      of carbohydrates in biology. Carbohydrate microarrays, fluorescent
      neoglycoconjugate probes, and aminoglycoside antibiotic microarrays are among the
      many new tools becoming available to glycobiologists.

PMID- 15457539
TI  - Dynamic chemical instabilities in living cells may provide a novel route in drug
      development.

PMID- 15457540
TI  - Providing psychosocial support for breast cancer patients based on screening for
      distress within a consultation-liaison service.
AB  - In a consecutive sample of 100 breast cancer patients undergoing radiotherapy,
      cancer-related distress was assessed with the Hospital Anxiety and Depression
      Scale and patients' interest in and acceptance of psychosocial support with the
      Questionnaire for Psychosocial Support and the European Consultation Liaison
      Workgroup documentation form. 31% of the patients suffered moderate to severe
      anxiety and/or depression and 42% expressed interest in supportive counselling.
      The wish for psychosocial support did not correlate with distress (moderate or
      severe anxiety and/or depression; Kappa = 0.06; P = 0.560). Patients with
      elevated levels of distress and/or those expressing a wish for psychosocial
      support were offered counselling by a psychotherapist and a social worker within
      the framework of a liaison service; 69% of the 58 patients offered such support
      accepted it. We conclude that screening instruments are helpful in identifying
      and consequently offering support to patients in need of counselling.

PMID- 15457541
TI  - Association of female aging with decreased parthenogenetic activation, raised
      MPF, and MAPKs activities and reduced levels of glutathione S-transferases
      activity and thiols in mouse oocytes.
AB  - This study aims to determine in the mouse whether oocytes from reproductively old
      females exhibit a different susceptibility to be parthenogenetically activated
      when compared to oocytes from young females. At the age of 10-12 (young-female
      group) or 60-62 (old-female group) weeks, hybrid female mice were superovulated
      using pregnant mare's serum gonadotropin (PMSG) followed by human chorionic
      gonadotropin (hCG) 48 hr later. After removing the cumulus cells, oocytes were
      exposed to any of two different activating protocols: (a) 6-min exposure to 8%
      ethanol; and (b) treatment with 200 microM thimerosal for 15 min followed by 8 mM
      dithiothreitol (DTT) for 30 min. Oocytes from old female mice displayed (1) lower
      total percentage of parthenogenetic activation and extrusion of the second polar
      body after treatment with either thimerosal + DTT or ethanol; (2) higher M-phase
      promoting factor (MPF) and mitogen-activated protein kinases (MAPKs) activities;
      and (3) lower intracytoplasmic levels of glutathione S-transferases (GSTs)
      activity and thiols than oocytes from young females. These data show that female
      aging is associated with higher resistance of oocytes to be parthenogenetically
      activated, higher MPF and MAPKs activities and lower intracytoplasmic levels of
      GSTs activity and thiols.